Keyword: time factors
2019 (2)
Hospital Costs Related to Early Extubation After Infant Cardiac Surgery. McHugh, K. E., Mahle, W. T., Hall, M. A., Scheurer, M. A., Moga, M., Triedman, J., Nicolson, S. C., Amula, V., Cooper, D. S., Schamberger, M., Wolf, M., Shekerdemian, L., Burns, K. M., Ash, K. E., Hipp, D. M., Pasquali, S. K., & Pediatric Heart Network Investigators The Annals of Thoracic Surgery, 107(5):1421–1426, 2019.
doi abstract bibtex
doi abstract bibtex
BACKGROUND: The Pediatric Heart Network Collaborative Learning Study (PHN CLS) increased early extubation rates after infant tetralogy of Fallot (TOF) and coarctation of the aorta (CoA) repair across participating sites by implementing a clinical practice guideline (CPG). The impact of the CPG on hospital costs has not been studied. METHODS: PHN CLS clinical data were linked to cost data from Children's Hospital Association by matching on indirect identifiers. Hospital costs were evaluated across active and control sites in the pre- and post-CPG periods using generalized linear mixed-effects models. A difference-in-difference approach was used to assess whether changes in cost observed in active sites were beyond secular trends in control sites. RESULTS: Data were successfully linked on 410 of 428 eligible patients (96%) from four active and four control sites. Mean adjusted cost per case for TOF repair was significantly reduced in the post-CPG period at active sites (\$42,833 vs \$56,304, p \textless 0.01) and unchanged at control sites (\$47,007 vs \$46,476, p = 0.91), with an overall cost reduction of 27% in active versus control sites (p = 0.03). Specific categories of cost reduced in the TOF cohort included clinical (-66%, p \textless 0.01), pharmacy (-46%, p = 0.04), lab (-44%, p \textless 0.01), and imaging (-32%, p \textless 0.01). There was no change in costs for CoA repair at active or control sites. CONCLUSIONS: The early extubation CPG was associated with a reduction in hospital costs for infants undergoing repair of TOF but not CoA. This CPG represents an opportunity to both optimize clinical outcome and reduce costs for certain infant cardiac surgeries.
@article{mchugh_hospital_2019,
title = {Hospital {Costs} {Related} to {Early} {Extubation} {After} {Infant} {Cardiac} {Surgery}},
volume = {107},
issn = {1552-6259},
doi = {10.1016/j.athoracsur.2018.10.019},
abstract = {BACKGROUND: The Pediatric Heart Network Collaborative Learning Study (PHN CLS) increased early extubation rates after infant tetralogy of Fallot (TOF) and coarctation of the aorta (CoA) repair across participating sites by implementing a clinical practice guideline (CPG). The impact of the CPG on hospital costs has not been studied.
METHODS: PHN CLS clinical data were linked to cost data from Children's Hospital Association by matching on indirect identifiers. Hospital costs were evaluated across active and control sites in the pre- and post-CPG periods using generalized linear mixed-effects models. A difference-in-difference approach was used to assess whether changes in cost observed in active sites were beyond secular trends in control sites.
RESULTS: Data were successfully linked on 410 of 428 eligible patients (96\%) from four active and four control sites. Mean adjusted cost per case for TOF repair was significantly reduced in the post-CPG period at active sites (\$42,833 vs \$56,304, p {\textless} 0.01) and unchanged at control sites (\$47,007 vs \$46,476, p = 0.91), with an overall cost reduction of 27\% in active versus control sites (p = 0.03). Specific categories of cost reduced in the TOF cohort included clinical (-66\%, p {\textless} 0.01), pharmacy (-46\%, p = 0.04), lab (-44\%, p {\textless} 0.01), and imaging (-32\%, p {\textless} 0.01). There was no change in costs for CoA repair at active or control sites.
CONCLUSIONS: The early extubation CPG was associated with a reduction in hospital costs for infants undergoing repair of TOF but not CoA. This CPG represents an opportunity to both optimize clinical outcome and reduce costs for certain infant cardiac surgeries.},
language = {eng},
number = {5},
journal = {The Annals of Thoracic Surgery},
author = {McHugh, Kimberly E. and Mahle, William T. and Hall, Matthew A. and Scheurer, Mark A. and Moga, Michael-Alice and Triedman, John and Nicolson, Susan C. and Amula, Venugopal and Cooper, David S. and Schamberger, Marcus and Wolf, Michael and Shekerdemian, Lara and Burns, Kristin M. and Ash, Kathleen E. and Hipp, Dustin M. and Pasquali, Sara K. and {Pediatric Heart Network Investigators}},
year = {2019},
pmid = {30458158},
pmcid = {PMC6545192},
keywords = {Age Factors, Airway Extubation, Aortic Coarctation, Cardiac Surgical Procedures, Female, Hospital Costs, Hospitalization, Humans, Infant, Infant, Newborn, Male, Retrospective Studies, Tetralogy of Fallot, Time Factors},
pages = {1421--1426}
}Sustainability of Infant Cardiac Surgery Early Extubation Practices After Implementation and Study. Gaies, M., Pasquali, S. K., Nicolson, S. C., Shekerdemian, L., Witte, M., Wolf, M., Zhang, W., Donohue, J. E., Mahle, W. T., & Pediatric Heart Network Investigators The Annals of Thoracic Surgery, 107(5):1427–1433, 2019.
doi abstract bibtex
doi abstract bibtex
BACKGROUND: The Pediatric Heart Network Collaborative Learning Study (PHN CLS) successfully changed practice at four hospitals to increase the rate of early extubation within 6 hours after infant heart surgery. It is unknown whether this practice continued after study completion. METHODS: We linked the PHN CLS dataset to the Pediatric Cardiac Critical Care Consortium registry to compare outcomes at four active hospitals between the study period (post-clinical practice guideline [CPG]) and the first year after study completion (follow-up) after a 3-month washout. Inclusion and exclusion criteria were the same across eras. Primary outcome was early extubation rate after tetralogy of Fallot or aortic coarctation repair. Secondary outcomes included time to first extubation and intensive care and hospital lengths of stay. RESULTS: There were 121 patients in the post-CPG era and 139 patients in the follow-up era with no difference in patient characteristics or operation subtypes. Post-CPG early extubation rate declined from 67% to 30% in follow-up (p \textless 0.0001); time to first extubation increased (4.5 versus 13.5 hours, p \textless 0.0001). One hospital maintained the rate of early extubation (72% versus 67%), whereas the other three hospitals had significantly lower rates in follow-up (p \textless 0.02 for each). Intensive care (2.8 versus 2.9 days) and postoperative hospital (6 versus 5 days) stays did not differ between eras (p \textgreater 0.05 for both). Findings were consistent across operation subtypes. CONCLUSIONS: Extubation practice in the first year of follow-up after the PHN CLS reverted toward prestudy levels. One of four hospitals maintained its early extubation strategy, suggesting that specific implementation and maintenance approaches may effectively sustain impact from quality initiatives.
@article{gaies_sustainability_2019,
title = {Sustainability of {Infant} {Cardiac} {Surgery} {Early} {Extubation} {Practices} {After} {Implementation} and {Study}},
volume = {107},
issn = {1552-6259},
doi = {10.1016/j.athoracsur.2018.09.024},
abstract = {BACKGROUND: The Pediatric Heart Network Collaborative Learning Study (PHN CLS) successfully changed practice at four hospitals to increase the rate of early extubation within 6 hours after infant heart surgery. It is unknown whether this practice continued after study completion.
METHODS: We linked the PHN CLS dataset to the Pediatric Cardiac Critical Care Consortium registry to compare outcomes at four active hospitals between the study period (post-clinical practice guideline [CPG]) and the first year after study completion (follow-up) after a 3-month washout. Inclusion and exclusion criteria were the same across eras. Primary outcome was early extubation rate after tetralogy of Fallot or aortic coarctation repair. Secondary outcomes included time to first extubation and intensive care and hospital lengths of stay.
RESULTS: There were 121 patients in the post-CPG era and 139 patients in the follow-up era with no difference in patient characteristics or operation subtypes. Post-CPG early extubation rate declined from 67\% to 30\% in follow-up (p {\textless} 0.0001); time to first extubation increased (4.5 versus 13.5 hours, p {\textless} 0.0001). One hospital maintained the rate of early extubation (72\% versus 67\%), whereas the other three hospitals had significantly lower rates in follow-up (p {\textless} 0.02 for each). Intensive care (2.8 versus 2.9 days) and postoperative hospital (6 versus 5 days) stays did not differ between eras (p {\textgreater} 0.05 for both). Findings were consistent across operation subtypes.
CONCLUSIONS: Extubation practice in the first year of follow-up after the PHN CLS reverted toward prestudy levels. One of four hospitals maintained its early extubation strategy, suggesting that specific implementation and maintenance approaches may effectively sustain impact from quality initiatives.},
language = {eng},
number = {5},
journal = {The Annals of Thoracic Surgery},
author = {Gaies, Michael and Pasquali, Sara K. and Nicolson, Susan C. and Shekerdemian, Lara and Witte, Madolin and Wolf, Michael and Zhang, Wenying and Donohue, Janet E. and Mahle, William T. and {Pediatric Heart Network Investigators}},
year = {2019},
pmid = {30391249},
keywords = {Airway Extubation, Aortic Coarctation, Cardiac Surgical Procedures, Clinical Protocols, Female, Follow-Up Studies, Guideline Adherence, Humans, Infant, Infant, Newborn, Length of Stay, Male, Postoperative Care, Practice Patterns, Physicians', Tetralogy of Fallot, Time Factors, Treatment Outcome},
pages = {1427--1433}
}2018 (2)
Corticosteroids Reduce Risk of Death Within 28 Days for Patients With Severe Alcoholic Hepatitis, Compared With Pentoxifylline or Placebo-a Meta-analysis of Individual Data. Louvet A, Thursz MR, Kim DJ, Labreuche J, Atkinson S, Sidhu SS, O''''Grady JG, Akriviadis E, Sinakos E, Carithers RL, Ramond MJ, Maddrey WC, Morgan TR, Duhamel A, & Mathurin P Gastroenterology, 2018.
![Corticosteroids Reduce Risk of Death Within 28 Days for Patients With Severe Alcoholic Hepatitis, Compared With Pentoxifylline or Placebo-a Meta-analysis of Individual Data. [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi bibtex
Paper doi bibtex @article{louvet_a_corticosteroids_2018,
title = {Corticosteroids Reduce Risk of Death Within 28 Days for Patients With Severe Alcoholic Hepatitis, Compared With Pentoxifylline or Placebo-a Meta-analysis of Individual Data.},
issn = {1528-0012},
url = {http://www.ncbi.nlm.nih.gov/pubmed/29738698},
DOI = {10.1053/j.gastro.2018.05.011},
Language = {English},
Journal = {Gastroenterology},
author = {{Louvet A} and {Thursz MR} and {Kim DJ} and {Labreuche J} and {Atkinson S} and {Sidhu SS} and {O''''Grady JG} and {Akriviadis E} and {Sinakos E} and {Carithers RL} and {Ramond MJ} and {Maddrey WC} and {Morgan TR} and {Duhamel A} and {Mathurin P}},
year = {2018},
keywords = {Drug Therapy, Combination/methods, Glucocorticoids/therapeutic use*, Hepatitis, Alcoholic/drug therapy*, Hepatitis, Alcoholic/mortality, Humans, Pentoxifylline/therapeutic use*, Placebos/therapeutic use, Prednisolone/therapeutic use, Randomized Controlled Trials as Topic, Severity of Illness Index, Survival Analysis, Time Factors, Treatment Outcome},
}Role of hydrotherapy in the amelioration of oxidant-antioxidant status in rheumatoid arthritis patients. Mateen, S., Moin, S., Khan, A. Q., Zafar, A., Fatima, N., & Shahzad, S. International Journal of Rheumatic Diseases, 21(10):1822–1830, October, 2018.
doi abstract bibtex
doi abstract bibtex
AIM: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease. Reactive oxygen species (ROS) are involved in the pathophysiology of RA. Moderate intensity exercises have been reported to have anti-oxidant and anti-inflammatory effects. The aim of this study was to evaluate the effect of hydrotherapy on oxidant-antioxidant status in RA patients. METHODS: Forty RA patients and 30 age- and sex-matched healthy controls were included in this study. RA patients were subdivided into two groups: the first group (n = 20) received treatment with conventional RA drugs, while the second group (n = 20) received hydrotherapy along with the conventional drugs for a period of 12 weeks. Disease Activity Score of 28 joints (DAS-28), ROS level, protein oxidation, lipid peroxidation, DNA damage and the activities of antioxidant enzymes were evaluated before and after 12 weeks of treatment. RESULTS: RA patients showed a significant change in the oxidative stress biomarkers (ROS, P \textless 0.01; ferric reducing antioxidant potential, P \textless 0.001; malondialdehyde, P \textless 0.01; protein carbonyl, P \textless 0.001; tail length, P \textless 0.05) and decrease in the activities of anti-oxidant enzymes (superoxide dismutase [SOD], P \textless 0.01; glutathione peroxidase [GPx], P \textless 0.001). Conventional drug treatment has not produced any significant change in these parameters. However, cotreatment of drugs with hydrotherapy has decreased protein, lipid and DNA oxidation by increasing the activities of antioxidant enzymes (SOD and GPx). CONCLUSION: Our results indicate that hydrotherapy along with drugs has reduced the severity of disease (DAS-28) by ameliorating the oxidant-antioxidant status in RA patients. Thus, in addition to conventional drugs, RA patients should be advised to have hydrotherapy (moderate intensity exercise) in their treatment regimen.
@article{mateen_role_2018,
title = {Role of hydrotherapy in the amelioration of oxidant-antioxidant status in rheumatoid arthritis patients},
volume = {21},
issn = {1756-185X},
doi = {10.1111/1756-185X.13118},
abstract = {AIM: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease. Reactive oxygen species (ROS) are involved in the pathophysiology of RA. Moderate intensity exercises have been reported to have anti-oxidant and anti-inflammatory effects. The aim of this study was to evaluate the effect of hydrotherapy on oxidant-antioxidant status in RA patients.
METHODS: Forty RA patients and 30 age- and sex-matched healthy controls were included in this study. RA patients were subdivided into two groups: the first group (n = 20) received treatment with conventional RA drugs, while the second group (n = 20) received hydrotherapy along with the conventional drugs for a period of 12 weeks. Disease Activity Score of 28 joints (DAS-28), ROS level, protein oxidation, lipid peroxidation, DNA damage and the activities of antioxidant enzymes were evaluated before and after 12 weeks of treatment.
RESULTS: RA patients showed a significant change in the oxidative stress biomarkers (ROS, P {\textless} 0.01; ferric reducing antioxidant potential, P {\textless} 0.001; malondialdehyde, P {\textless} 0.01; protein carbonyl, P {\textless} 0.001; tail length, P {\textless} 0.05) and decrease in the activities of anti-oxidant enzymes (superoxide dismutase [SOD], P {\textless} 0.01; glutathione peroxidase [GPx], P {\textless} 0.001). Conventional drug treatment has not produced any significant change in these parameters. However, cotreatment of drugs with hydrotherapy has decreased protein, lipid and DNA oxidation by increasing the activities of antioxidant enzymes (SOD and GPx).
CONCLUSION: Our results indicate that hydrotherapy along with drugs has reduced the severity of disease (DAS-28) by ameliorating the oxidant-antioxidant status in RA patients. Thus, in addition to conventional drugs, RA patients should be advised to have hydrotherapy (moderate intensity exercise) in their treatment regimen.},
language = {eng},
number = {10},
journal = {International Journal of Rheumatic Diseases},
author = {Mateen, Somaiya and Moin, Shagufta and Khan, Abdul Q. and Zafar, Atif and Fatima, Naureen and Shahzad, Sumayya},
month = oct,
year = {2018},
pmid = {28612349},
keywords = {Adult, Antirheumatic Agents, Arthritis, Rheumatoid, Biomarkers, Case-Control Studies, Combined Modality Therapy, DNA Damage, Enzymes, Female, Humans, Hydrotherapy, Lipid Peroxidation, Male, Middle Aged, Oxidative Stress, Protein Carbonylation, Reactive Oxygen Species, Time Factors, Treatment Outcome, antioxidants, hydrotherapy, moderate intensity exercises, oxidative stress, rheumatoid arthritis},
pages = {1822--1830},
}2016 (4)
Proteomic Analysis of the Spatio-temporal Based Molecular Kinetics of Acute Spinal Cord Injury Identifies a Time- and Segment-specific Window for Effective Tissue Repair. Devaux, S., Cizkova, D., Quanico, J., Franck, J., Nataf, S., Pays, L., Hauberg-Lotte, L., Maass, P., Kobarg, J. H., Kobeissy, F., Meriaux, C., Wisztorski, M., Slovinska, L., Blasko, J., Cigankova, V., Fournier, I., & Salzet, M. Mol Cell Proteomics, 15(8):2641–70, 2016.
Paper doi abstract bibtex
Paper doi abstract bibtex Spinal cord injury (SCI) represents a major debilitating health issue with a direct socioeconomic burden on the public and private sectors worldwide. Although several studies have been conducted to identify the molecular progression of injury sequel due from the lesion site, still the exact underlying mechanisms and pathways of injury development have not been fully elucidated. In this work, based on OMICs, 3D matrix-assisted laser desorption ionization (MALDI) imaging, cytokines arrays, confocal imaging we established for the first time that molecular and cellular processes occurring after SCI are altered between the lesion proximity, i.e. rostral and caudal segments nearby the lesion (R1-C1) whereas segments distant from R1-C1, i.e. R2-C2 and R3-C3 levels coexpressed factors implicated in neurogenesis. Delay in T regulators recruitment between R1 and C1 favor discrepancies between the two segments. This is also reinforced by presence of neurites outgrowth inhibitors in C1, absent in R1. Moreover, the presence of immunoglobulins (IgGs) in neurons at the lesion site at 3 days, validated by mass spectrometry, may present additional factor that contributes to limited regeneration. Treatment in vivo with anti-CD20 one hour after SCI did not improve locomotor function and decrease IgG expression. These results open the door of a novel view of the SCI treatment by considering the C1 as the therapeutic target.
@article{devaux_proteomic_2016,
title = {Proteomic {Analysis} of the {Spatio}-temporal {Based} {Molecular} {Kinetics} of {Acute} {Spinal} {Cord} {Injury} {Identifies} a {Time}- and {Segment}-specific {Window} for {Effective} {Tissue} {Repair}},
volume = {15},
issn = {1535-9484 (Electronic) 1535-9476 (Linking)},
url = {http://www.ncbi.nlm.nih.gov/pubmed/27250205},
doi = {10.1074/mcp.M115.057794},
abstract = {Spinal cord injury (SCI) represents a major debilitating health issue with a direct socioeconomic burden on the public and private sectors worldwide. Although several studies have been conducted to identify the molecular progression of injury sequel due from the lesion site, still the exact underlying mechanisms and pathways of injury development have not been fully elucidated. In this work, based on OMICs, 3D matrix-assisted laser desorption ionization (MALDI) imaging, cytokines arrays, confocal imaging we established for the first time that molecular and cellular processes occurring after SCI are altered between the lesion proximity, i.e. rostral and caudal segments nearby the lesion (R1-C1) whereas segments distant from R1-C1, i.e. R2-C2 and R3-C3 levels coexpressed factors implicated in neurogenesis. Delay in T regulators recruitment between R1 and C1 favor discrepancies between the two segments. This is also reinforced by presence of neurites outgrowth inhibitors in C1, absent in R1. Moreover, the presence of immunoglobulins (IgGs) in neurons at the lesion site at 3 days, validated by mass spectrometry, may present additional factor that contributes to limited regeneration. Treatment in vivo with anti-CD20 one hour after SCI did not improve locomotor function and decrease IgG expression. These results open the door of a novel view of the SCI treatment by considering the C1 as the therapeutic target.},
number = {8},
journal = {Mol Cell Proteomics},
author = {Devaux, S. and Cizkova, D. and Quanico, J. and Franck, J. and Nataf, S. and Pays, L. and Hauberg-Lotte, L. and Maass, P. and Kobarg, J. H. and Kobeissy, F. and Meriaux, C. and Wisztorski, M. and Slovinska, L. and Blasko, J. and Cigankova, V. and Fournier, I. and Salzet, M.},
year = {2016},
keywords = {Animal, Animals, Biomarkers/*metabolism, Cytokines/*metabolism, Disease Models, Humans, Mass, Matrix-Assisted Laser Desorption-Ionization/methods, Protein Array Analysis, Protein Interaction Maps, Proteomics/*methods, Rats, Spectrometry, Spinal Cord Injuries/*metabolism, Time Factors},
pages = {2641--70},
}Enhancing prefrontal neuron activity enables associative learning of temporally disparate events. Volle, J., Yu, X., Sun, H., Tanninen, S. E., Insel, N., & Takehara-Nishiuchi, K. Cell reports, 15(11):2400–2410, June, 2016. PMID 27264170
doi bibtex
doi bibtex
Dynamics of Urinary Calprotectin after Renal Ischaemia. Ebbing, J., Seibert, F. S., Pagonas, N., Bauer, F., Miller, K., Kempkensteffen, C., Gunzel, K., Bachmann, A., Seifert, H. H., Rentsch, C. A., Ardelt, P., Wetterauer, C., Amico, P., Babel, N., & Westhoff, T. H. PloS one, 11(1):e0146395, 2016.
doi abstract bibtex
doi abstract bibtex
BACKGROUND: Urinary calprotectin has been identified as a promising biomarker for acute kidney injury. To date, however, the time-dependent changes of this parameter during acute kidney injury remain elusive. The aim of the present work was to define the time-course of urinary calprotectin secretion after ischaemia/reperfusion-induced kidney injury in comparison to neutrophil gelatinase-associated lipocalin, thereby monitoring the extent of tubular damage in nephron sparing surgery for kidney tumours. METHODS: The study population consisted of 42 patients. Thirty-two patients underwent either open or endoscopic nephron sparing surgery for kidney tumours. During the surgery, the renal arterial pedicle was clamped with a median ischaemic time of 13 minutes (interquartile range, 4.5-20.3 minutes) in 26 patients. Ten retro-peritoneoscopic living donor nephrectomy patients and 6 nephron sparing surgery patients in whom the renal artery was not clamped served as controls. Urinary calprotectin and neutrophil gelatinase-associated lipocalin concentrations were repeatedly measured by enzyme-linked immunosorbent assay and assessed according to renal function parameters. RESULTS: Urinary concentrations of calprotectin and neutrophil gelatinase-associated lipocalin increased significantly after ischaemia/reperfusion injury, whereas concentrations remained unchanged after nephron sparing surgery without ischaemia/reperfusion injury and after kidney donation. Calprotectin and neutrophil gelatinase-associated lipocalin levels were significantly increased 2 and 8 hours, respectively, post-ischaemia. Both proteins reached maximal concentrations after 48 hours, followed by a subsequent persistent decrease. Maximal neutrophil gelatinase-associated lipocalin and calprotectin concentrations were 9-fold and 69-fold higher than their respective baseline values. The glomerular filtration rate was only transiently impaired at the first post-operative day after ischaemia/reperfusion injury (p = 0.049). CONCLUSION: Calprotectin and neutrophil gelatinase-associated lipocalin can be used to monitor clinical and sub-clinical tubular damage after nephron sparing surgery for kidney tumours. Urinary calprotectin concentrations start rising within 2 hours after ischaemia/reperfusion-induced kidney injury.
@article{ebbing_dynamics_2016,
title = {Dynamics of {Urinary} {Calprotectin} after {Renal} {Ischaemia}.},
volume = {11},
issn = {1932-6203 1932-6203},
doi = {10.1371/journal.pone.0146395},
abstract = {BACKGROUND: Urinary calprotectin has been identified as a promising biomarker for acute kidney injury. To date, however, the time-dependent changes of this parameter during acute kidney injury remain elusive. The aim of the present work was to define the time-course of urinary calprotectin secretion after ischaemia/reperfusion-induced kidney injury in comparison to neutrophil gelatinase-associated lipocalin, thereby monitoring the extent of tubular damage in nephron sparing surgery for kidney tumours. METHODS: The study population consisted of 42 patients. Thirty-two patients underwent either open or endoscopic nephron sparing surgery for kidney tumours. During the surgery, the renal arterial pedicle was clamped with a median ischaemic time of 13 minutes (interquartile range, 4.5-20.3 minutes) in 26 patients. Ten retro-peritoneoscopic living donor nephrectomy patients and 6 nephron sparing surgery patients in whom the renal artery was not clamped served as controls. Urinary calprotectin and neutrophil gelatinase-associated lipocalin concentrations were repeatedly measured by enzyme-linked immunosorbent assay and assessed according to renal function parameters. RESULTS: Urinary concentrations of calprotectin and neutrophil gelatinase-associated lipocalin increased significantly after ischaemia/reperfusion injury, whereas concentrations remained unchanged after nephron sparing surgery without ischaemia/reperfusion injury and after kidney donation. Calprotectin and neutrophil gelatinase-associated lipocalin levels were significantly increased 2 and 8 hours, respectively, post-ischaemia. Both proteins reached maximal concentrations after 48 hours, followed by a subsequent persistent decrease. Maximal neutrophil gelatinase-associated lipocalin and calprotectin concentrations were 9-fold and 69-fold higher than their respective baseline values. The glomerular filtration rate was only transiently impaired at the first post-operative day after ischaemia/reperfusion injury (p = 0.049). CONCLUSION: Calprotectin and neutrophil gelatinase-associated lipocalin can be used to monitor clinical and sub-clinical tubular damage after nephron sparing surgery for kidney tumours. Urinary calprotectin concentrations start rising within 2 hours after ischaemia/reperfusion-induced kidney injury.},
language = {eng},
number = {1},
journal = {PloS one},
author = {Ebbing, Jan and Seibert, Felix S. and Pagonas, Nikolaos and Bauer, Frederic and Miller, Kurt and Kempkensteffen, Carsten and Gunzel, Karsten and Bachmann, Alexander and Seifert, Hans H. and Rentsch, Cyrill A. and Ardelt, Peter and Wetterauer, Christian and Amico, Patrizia and Babel, Nina and Westhoff, Timm H.},
year = {2016},
pmid = {26745147},
pmcid = {PMC4706321},
keywords = {*Kidney Transplantation, Acute-Phase Proteins/*urine, Adult, Aged, Biomarkers/urine, Carcinoma, Renal Cell/blood supply/pathology/surgery/*urine, Case-Control Studies, Female, Glomerular Filtration Rate, Humans, Kidney Neoplasms/blood supply/pathology/surgery/*urine, Kidney/blood supply/metabolism/pathology/surgery, Leukocyte L1 Antigen Complex/*urine, Lipocalin-2, Lipocalins/*urine, Male, Middle Aged, Neoplasm Staging, Nephrectomy/methods, Proto-Oncogene Proteins/*urine, Renal Artery/surgery, Reperfusion Injury/diagnosis/pathology/surgery/*urine, Time Factors},
pages = {e0146395}
}Comparison of Transcutaneous Electrical Nerve Stimulation and Parasternal Block for Postoperative Pain Management after Cardiac Surgery. Ozturk, N. K., Baki, E. D., Kavakli, A. S., Sahin, A. S., Ayoglu, R. U., Karaveli, A., Emmiler, M., Inanoglu, K., & Karsli, B. Pain research & management, 2016(9612504):4261949, 2016. Ozturk, Nilgun Kavrut. Department of Anesthesiology and Reanimation, Antalya Education and Research Hospital, Varlik Mahallesi, Kazim Karabekir Cadde, 07100 Antalya, Turkey. Baki, Elif Dogan. Department of Anesthesiology and Reanimation, Afyon Kocatepe University, Faculty of Medicine, Afyon, Turkey. Kavakli, Ali Sait. Department of Anesthesiology and Reanimation, Antalya Education and Research Hospital, Varlik Mahallesi, Kazim Karabekir Cadde, 07100 Antalya, Turkey. Sahin, Ayca Sultan. Department of Anesthesiology and Reanimation, Antalya Education and Research Hospital, Varlik Mahallesi, Kazim Karabekir Cadde, 07100 Antalya, Turkey. Ayoglu, Raif Umut. Department of Cardiovascular Surgery, Antalya Education and Research Hospital, 07100 Antalya, Turkey. Karaveli, Arzu. Department of Anesthesiology and Reanimation, Antalya Education and Research Hospital, Varlik Mahallesi, Kazim Karabekir Cadde, 07100 Antalya, Turkey. Emmiler, Mustafa. Department of Cardiovascular Surgery, Antalya Education and Research Hospital, 07100 Antalya, Turkey. Inanoglu, Kerem. Department of Anesthesiology and Reanimation, Antalya Education and Research Hospital, Varlik Mahallesi, Kazim Karabekir Cadde, 07100 Antalya, Turkey. Karsli, Bilge. Department of Algology, Akdeniz University, Faculty of Medicine, 07100 Antalya, Turkey.
abstract bibtex
abstract bibtex
Background. Parasternal block and transcutaneous electrical nerve stimulation (TENS) have been demonstrated to produce effective analgesia and reduce postoperative opioid requirements in patients undergoing cardiac surgery. Objectives. To compare the effectiveness of TENS and parasternal block on early postoperative pain after cardiac surgery. Methods. One hundred twenty patients undergoing cardiac surgery were enrolled in the present randomized, controlled prospective study. Patients were assigned to three treatment groups: parasternal block, intermittent TENS application, or a control group. Results. Pain scores recorded 4h, 5h, 6h, 7h, and 8h postoperatively were lower in the parasternal block group than in the TENS and control groups. Total morphine consumption was also lower in the parasternal block group than in the TENS and control groups. It was also significantly lower in the TENS group than in the control group. There were no statistical differences among the groups regarding the extubation time, rescue analgesic medication, length of intensive care unit stay, or length of hospital stay. Conclusions. Parasternal block was more effective than TENS in the management of early postoperative pain and the reduction of opioid requirements in patients who underwent cardiac surgery through median sternotomy. This trial is registered with Clinicaltrials.gov number NCT02725229.
@article{ozturk_comparison_2016,
title = {Comparison of {Transcutaneous} {Electrical} {Nerve} {Stimulation} and {Parasternal} {Block} for {Postoperative} {Pain} {Management} after {Cardiac} {Surgery}.},
volume = {2016},
issn = {1918-1523},
abstract = {Background. Parasternal block and transcutaneous electrical nerve stimulation (TENS) have been demonstrated to produce effective analgesia and reduce postoperative opioid requirements in patients undergoing cardiac surgery. Objectives. To compare the effectiveness of TENS and parasternal block on early postoperative pain after cardiac surgery. Methods. One hundred twenty patients undergoing cardiac surgery were enrolled in the present randomized, controlled prospective study. Patients were assigned to three treatment groups: parasternal block, intermittent TENS application, or a control group. Results. Pain scores recorded 4h, 5h, 6h, 7h, and 8h postoperatively were lower in the parasternal block group than in the TENS and control groups. Total morphine consumption was also lower in the parasternal block group than in the TENS and control groups. It was also significantly lower in the TENS group than in the control group. There were no statistical differences among the groups regarding the extubation time, rescue analgesic medication, length of intensive care unit stay, or length of hospital stay. Conclusions. Parasternal block was more effective than TENS in the management of early postoperative pain and the reduction of opioid requirements in patients who underwent cardiac surgery through median sternotomy. This trial is registered with Clinicaltrials.gov number NCT02725229.},
number = {9612504},
journal = {Pain research \& management},
author = {Ozturk, Nilgun Kavrut and Baki, Elif Dogan and Kavakli, Ali Sait and Sahin, Ayca Sultan and Ayoglu, Raif Umut and Karaveli, Arzu and Emmiler, Mustafa and Inanoglu, Kerem and Karsli, Bilge},
year = {2016},
note = {Ozturk, Nilgun Kavrut. Department of Anesthesiology and Reanimation, Antalya Education and Research Hospital, Varlik Mahallesi, Kazim Karabekir Cadde, 07100 Antalya, Turkey.
Baki, Elif Dogan. Department of Anesthesiology and Reanimation, Afyon Kocatepe University, Faculty of Medicine, Afyon, Turkey.
Kavakli, Ali Sait. Department of Anesthesiology and Reanimation, Antalya Education and Research Hospital, Varlik Mahallesi, Kazim Karabekir Cadde, 07100 Antalya, Turkey.
Sahin, Ayca Sultan. Department of Anesthesiology and Reanimation, Antalya Education and Research Hospital, Varlik Mahallesi, Kazim Karabekir Cadde, 07100 Antalya, Turkey.
Ayoglu, Raif Umut. Department of Cardiovascular Surgery, Antalya Education and Research Hospital, 07100 Antalya, Turkey.
Karaveli, Arzu. Department of Anesthesiology and Reanimation, Antalya Education and Research Hospital, Varlik Mahallesi, Kazim Karabekir Cadde, 07100 Antalya, Turkey.
Emmiler, Mustafa. Department of Cardiovascular Surgery, Antalya Education and Research Hospital, 07100 Antalya, Turkey.
Inanoglu, Kerem. Department of Anesthesiology and Reanimation, Antalya Education and Research Hospital, Varlik Mahallesi, Kazim Karabekir Cadde, 07100 Antalya, Turkey.
Karsli, Bilge. Department of Algology, Akdeniz University, Faculty of Medicine, 07100 Antalya, Turkey.},
keywords = {*Cardiac Surgical Procedures/ae [Adverse Effects], *Nerve Block/mt [Methods], *Pain, Postoperative/et [Etiology], *Pain, Postoperative/th [Therapy], *Transcutaneous Electric Nerve Stimulation/mt [Methods], Adjuvants, Anesthesia/tu [Therapeutic Use], Diazepam/tu [Therapeutic Use], Heart Diseases/su [Surgery], Humans, Prospective Studies, Time Factors, adolescent, adult, aged, female, male, middle aged, treatment outcome, visual analog scale, young adult},
pages = {4261949}
}2015 (1)
Exercise therapy may postpone total hip replacement surgery in patients with hip osteoarthritis: a long-term follow-up of a randomised trial. Svege, I., Nordsletten, L., Fernandes, L., & Risberg, M. A. Annals of the Rheumatic Diseases, 74(1):164–169, January, 2015.
doi abstract bibtex
doi abstract bibtex
BACKGROUND: Exercise treatment is recommended for all patients with hip osteoarthritis (OA), but its effect on the long-term need for total hip replacement (THR) is unknown. METHODS: We conducted a long-term follow-up of a randomised trial investigating the efficacy of exercise therapy and patient education versus patient education only on the 6-year cumulative survival of the native hip to THR in 109 patients with symptomatic and radiographic hip OA. Results regarding the primary outcome measure of the trial, self-reported pain at 16 months follow-up, have been reported previously. RESULTS: There were no group differences at baseline. The response rate at follow-up was 94%. 22 patients in the group receiving both exercise therapy and patient education and 31 patients in the group receiving patient education only underwent THR during the follow-up period, giving a 6-year cumulative survival of the native hip of 41% and 25%, respectively (p=0.034). The HR for survival of the native hip was 0.56 (CI 0.32 to 0.96) for the exercise therapy group compared with the control group. Median time to THR was 5.4 and 3.5 years, respectively. The exercise therapy group had better self-reported hip function prior to THR or end of study, but no significant differences were found for pain and stiffness. CONCLUSIONS: Our findings in this explanatory study suggest that exercise therapy in addition to patient education can reduce the need for THR by 44% in patients with hip OA. ClinicalTrials.gov number NCT00319423 (original project protocol) and NCT01338532 (additional protocol for long-term follow-up).
@article{svege_exercise_2015,
title = {Exercise therapy may postpone total hip replacement surgery in patients with hip osteoarthritis: a long-term follow-up of a randomised trial},
volume = {74},
issn = {1468-2060},
shorttitle = {Exercise therapy may postpone total hip replacement surgery in patients with hip osteoarthritis},
doi = {10.1136/annrheumdis-2013-203628},
abstract = {BACKGROUND: Exercise treatment is recommended for all patients with hip osteoarthritis (OA), but its effect on the long-term need for total hip replacement (THR) is unknown.
METHODS: We conducted a long-term follow-up of a randomised trial investigating the efficacy of exercise therapy and patient education versus patient education only on the 6-year cumulative survival of the native hip to THR in 109 patients with symptomatic and radiographic hip OA. Results regarding the primary outcome measure of the trial, self-reported pain at 16 months follow-up, have been reported previously.
RESULTS: There were no group differences at baseline. The response rate at follow-up was 94\%. 22 patients in the group receiving both exercise therapy and patient education and 31 patients in the group receiving patient education only underwent THR during the follow-up period, giving a 6-year cumulative survival of the native hip of 41\% and 25\%, respectively (p=0.034). The HR for survival of the native hip was 0.56 (CI 0.32 to 0.96) for the exercise therapy group compared with the control group. Median time to THR was 5.4 and 3.5 years, respectively. The exercise therapy group had better self-reported hip function prior to THR or end of study, but no significant differences were found for pain and stiffness.
CONCLUSIONS: Our findings in this explanatory study suggest that exercise therapy in addition to patient education can reduce the need for THR by 44\% in patients with hip OA. ClinicalTrials.gov number NCT00319423 (original project protocol) and NCT01338532 (additional protocol for long-term follow-up).},
language = {eng},
number = {1},
journal = {Annals of the Rheumatic Diseases},
author = {Svege, Ida and Nordsletten, Lars and Fernandes, Linda and Risberg, May Arna},
month = jan,
year = {2015},
pmid = {24255546},
pmcid = {PMC4283660},
keywords = {Aged, Arthroplasty, Replacement, Hip, Exercise Therapy, Female, Follow-Up Studies, Humans, Male, Middle Aged, Orthopedic Surgery, Osteoarthritis, Osteoarthritis, Hip, Patient Education as Topic, Physcial therapy, Rehabilitation, Time Factors},
pages = {164--169},
}2014 (4)
ADHD prevalence estimates across three decades: an updated systematic review and meta-regression analysis. Polanczyk, G. V, Willcutt, E. G, Salum, G. A, Kieling, C., & Rohde, L. A International journal of epidemiology, 43(2):434–42, April, 2014.
Paper doi abstract bibtex
Paper doi abstract bibtex BACKGROUND: Previous studies have identified significant variability in attention-deficit / hyperactivity disorder (ADHD) prevalence estimates worldwide, largely explained by methodological procedures. However, increasing rates of ADHD diagnosis and treatment throughout the past few decades have fuelled concerns about whether the true prevalence of the disorder has increased over time. METHODS: We updated the two most comprehensive systematic reviews on ADHD prevalence available in the literature. Meta-regression analyses were conducted to test the effect of year of study in the context of both methodological variables that determined variability in ADHD prevalence (diagnostic criteria, impairment criterion and source of information), and the geographical location of studies. RESULTS: We identified 154 original studies and included 135 in the multivariate analysis. Methodological procedures investigated were significantly associated with heterogeneity of studies. Geographical location and year of study were not associated with variability in ADHD prevalence estimates. CONCLUSIONS: Confirming previous findings, variability in ADHD prevalence estimates is mostly explained by methodological characteristics of the studies. In the past three decades, there has been no evidence to suggest an increase in the number of children in the community who meet criteria for ADHD when standardized diagnostic procedures are followed.
@article{polanczyk_adhd_2014,
title = {{ADHD} prevalence estimates across three decades: an updated systematic review and meta-regression analysis.},
volume = {43},
issn = {1464-3685},
url = {http://ije.oxfordjournals.org/content/43/2/434.long},
doi = {10.1093/ije/dyt261},
abstract = {BACKGROUND: Previous studies have identified significant variability in attention-deficit / hyperactivity disorder (ADHD) prevalence estimates worldwide, largely explained by methodological procedures. However, increasing rates of ADHD diagnosis and treatment throughout the past few decades have fuelled concerns about whether the true prevalence of the disorder has increased over time.
METHODS: We updated the two most comprehensive systematic reviews on ADHD prevalence available in the literature. Meta-regression analyses were conducted to test the effect of year of study in the context of both methodological variables that determined variability in ADHD prevalence (diagnostic criteria, impairment criterion and source of information), and the geographical location of studies.
RESULTS: We identified 154 original studies and included 135 in the multivariate analysis. Methodological procedures investigated were significantly associated with heterogeneity of studies. Geographical location and year of study were not associated with variability in ADHD prevalence estimates.
CONCLUSIONS: Confirming previous findings, variability in ADHD prevalence estimates is mostly explained by methodological characteristics of the studies. In the past three decades, there has been no evidence to suggest an increase in the number of children in the community who meet criteria for ADHD when standardized diagnostic procedures are followed.},
number = {2},
urldate = {2015-03-01},
journal = {International journal of epidemiology},
author = {Polanczyk, Guilherme V and Willcutt, Erik G and Salum, Giovanni A and Kieling, Christian and Rohde, Luis A},
month = apr,
year = {2014},
pmid = {24464188},
keywords = {Attention Deficit Disorder with Hyperactivity, Attention Deficit Disorder with Hyperactivity: epi, Epidemiologic Methods, Global Health, Global Health: statistics \& numerical data, Humans, Time Factors},
pages = {434--42},
}Fatal unintentional non-fire-related carbon monoxide poisoning: England and Wales, 1979-2012. Fisher, D. S., Leonardi, G., & Flanagan, R. J. Clinical Toxicology (Philadelphia, Pa.), 52(3):166--170, March, 2014. 00006
doi abstract bibtex
doi abstract bibtex
CONTEXT: Unintentional carbon monoxide poisoning remains a significant cause of morbidity and mortality in England and Wales. METHODS. STUDY DESIGN: observational case series. Data on fatal carbon monoxide poisoning in England and Wales from 1979 to 2012 were obtained from coroner reports. Data on unintentional non-fire-related carbon monoxide poisoning were extracted and were analysed by year of registration of death, sex, age group, and whether death occurred at a private house, flat, associated garage, or residential caravan ('home'), or elsewhere. RESULTS AND DISCUSSION: There were 28,944 carbon monoxide-related deaths, of which 82% were male. Deaths increased from 965 (1979) to 1700 (1987), and then fell to 182 (2012). Of these 2208 (64% male) were recorded as unintentional non-fire-related deaths. Annual numbers of these latter deaths fell from 166 in 1979 to 25 in 2012 (i.e. from 3.37 to 0.44 per million population). Some 81 and 92% of such deaths in males and in females, respectively, occurred at 'home'. A clear preponderance of male versus female deaths was seen in the 10-19, 20-39 and 40-64 years age groups, with similar numbers of deaths in males and in females in the younger (\textless 1 and 1-9 year) and higher (65-79 and 80 + years) age groups. A higher proportion of these excess deaths in males occurred outside the deceased's 'home' in those aged 10-19, 20-39 and 40-64 years. CONCLUSION: Deaths from unintentional non-fire-related carbon monoxide poisoning are now much less common in England and Wales than in earlier years, but remain a cause for concern. Installation and proper maintenance of carbon monoxide alarms in dwellings and outhouses, for example, and education not only of the public, but also of health and other professionals as to the danger posed by carbon monoxide could help prevent such deaths.
@article{fisher_fatal_2014,
title = {Fatal unintentional non-fire-related carbon monoxide poisoning: {England} and {Wales}, 1979-2012},
volume = {52},
issn = {1556-9519},
shorttitle = {Fatal unintentional non-fire-related carbon monoxide poisoning},
doi = {10.3109/15563650.2014.887092},
abstract = {CONTEXT: Unintentional carbon monoxide poisoning remains a significant cause of morbidity and mortality in England and Wales. METHODS.
STUDY DESIGN: observational case series. Data on fatal carbon monoxide poisoning in England and Wales from 1979 to 2012 were obtained from coroner reports. Data on unintentional non-fire-related carbon monoxide poisoning were extracted and were analysed by year of registration of death, sex, age group, and whether death occurred at a private house, flat, associated garage, or residential caravan ('home'), or elsewhere.
RESULTS AND DISCUSSION: There were 28,944 carbon monoxide-related deaths, of which 82\% were male. Deaths increased from 965 (1979) to 1700 (1987), and then fell to 182 (2012). Of these 2208 (64\% male) were recorded as unintentional non-fire-related deaths. Annual numbers of these latter deaths fell from 166 in 1979 to 25 in 2012 (i.e. from 3.37 to 0.44 per million population). Some 81 and 92\% of such deaths in males and in females, respectively, occurred at 'home'. A clear preponderance of male versus female deaths was seen in the 10-19, 20-39 and 40-64 years age groups, with similar numbers of deaths in males and in females in the younger ({\textless} 1 and 1-9 year) and higher (65-79 and 80 + years) age groups. A higher proportion of these excess deaths in males occurred outside the deceased's 'home' in those aged 10-19, 20-39 and 40-64 years.
CONCLUSION: Deaths from unintentional non-fire-related carbon monoxide poisoning are now much less common in England and Wales than in earlier years, but remain a cause for concern. Installation and proper maintenance of carbon monoxide alarms in dwellings and outhouses, for example, and education not only of the public, but also of health and other professionals as to the danger posed by carbon monoxide could help prevent such deaths.},
language = {eng},
number = {3},
journal = {Clinical Toxicology (Philadelphia, Pa.)},
author = {Fisher, D. S. and Leonardi, G. and Flanagan, R. J.},
month = mar,
year = {2014},
pmid = {24533843},
note = {00006 },
keywords = {Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Carbon Monoxide Poisoning, Child, England, Female, Humans, Male, Middle Aged, Sex Characteristics, Time Factors, Wales},
pages = {166--170}
}Mass spectrometry footprinting reveals the structural rearrangements of cyanobacterial orange carotenoid protein upon light activation. Liu, H., Zhang, H., King, j. D., Wolf, N. R., Prado, M., Gross, M. L., & Blankenship, R. E. Biochimica Et Biophysica Acta, 1837(12):1955–1963, December, 2014.
doi abstract bibtex
doi abstract bibtex
The orange carotenoid protein (OCP), a member of the family of blue light photoactive proteins, is required for efficient photoprotection in many cyanobacteria. Photoexcitation of the carotenoid in the OCP results in structural changes within the chromophore and the protein to give an active red form of OCP that is required for phycobilisome binding and consequent fluorescence quenching. We characterized the light-dependent structural changes by mass spectrometry-based carboxyl footprinting and found that an α helix in the N-terminal extension of OCP plays a key role in this photoactivation process. Although this helix is located on and associates with the outside of the β-sheet core in the C-terminal domain of OCP in the dark, photoinduced changes in the domain structure disrupt this interaction. We propose that this mechanism couples light-dependent carotenoid conformational changes to global protein conformational dynamics in favor of functional phycobilisome binding, and is an essential part of the OCP photocycle.
@article{liu_mass_2014,
title = {Mass spectrometry footprinting reveals the structural rearrangements of cyanobacterial orange carotenoid protein upon light activation},
volume = {1837},
issn = {0006-3002},
doi = {10.1016/j.bbabio.2014.09.004},
abstract = {The orange carotenoid protein (OCP), a member of the family of blue light photoactive proteins, is required for efficient photoprotection in many cyanobacteria. Photoexcitation of the carotenoid in the OCP results in structural changes within the chromophore and the protein to give an active red form of OCP that is required for phycobilisome binding and consequent fluorescence quenching. We characterized the light-dependent structural changes by mass spectrometry-based carboxyl footprinting and found that an α helix in the N-terminal extension of OCP plays a key role in this photoactivation process. Although this helix is located on and associates with the outside of the β-sheet core in the C-terminal domain of OCP in the dark, photoinduced changes in the domain structure disrupt this interaction. We propose that this mechanism couples light-dependent carotenoid conformational changes to global protein conformational dynamics in favor of functional phycobilisome binding, and is an essential part of the OCP photocycle.},
language = {eng},
number = {12},
journal = {Biochimica Et Biophysica Acta},
author = {Liu, Haijun and Zhang, Hao and King, jeremy D. and Wolf, Nathan R. and Prado, Mindy and Gross, Michael L. and Blankenship, Robert E.},
month = dec,
year = {2014},
pmid = {25256653},
keywords = {Bacterial Proteins, Carbodiimides, Cyanobacteria, Glycine, Mass spectrometry, Models, Molecular, Orange carotenoid protein, Peptides, Photoactivation, Phycobilisomes, Protein Conformation, Protein Footprinting, Protein Structure, Secondary, Protein Structure, Tertiary, Spectrophotometry, Synechocystis, Time Factors, light, photoprotection, photosynthesis, phycobilisome},
pages = {1955--1963},
}Review of maintenance trials for major depressive disorder: a 25-year perspective from the US Food and Drug Administration. Borges, S., Chen, Y., Laughren, T. P, Temple, R., Patel, H. D, David, P. A, Mathis, M., Unger, E., Yang, P., & Khin, N. A The Journal of clinical psychiatry, 75(3):205–214, 2014.
Paper doi abstract bibtex
Paper doi abstract bibtex The maintenance efficacy of antidepressants is usually assessed in postmarketing studies with a randomized withdrawal design. This report explores differences in relapse rates, trial characteristics, and success rates in maintenance efficacy studies submitted to the US Food and Drug Administration (FDA) over a 25-year period. Clinical data from all maintenance trials with antidepressants submitted to FDA between 1987 and 2012. Efficacy data were compiled from 15 maintenance clinical trials in adults diagnosed with major depressive disorder according to DSM-III or DSM-IV criteria. Trial characteristics, relapse rates, and time to relapse in each study were examined. Relapse rates were significantly lower (P \textless .05) in the drug arm than in the placebo arm in every study, with a mean relapse rate difference of 18% and an average percent reduction in relapse rate of 52% compared to placebo. Only 6% of the relapse events occurred in the first 2 weeks of the double-blind phase. The separation between treatment arms continued to increase throughout the double-blind phase only in the trial with longest response stabilization period. Antidepressant maintenance trials have a high rate of success, indicating a benefit of continuing drug treatment after initial response to an antidepressant. This benefit appears to result mainly from a decreased rate of recurrent depression rather than from an effect of drug withdrawal in the placebo groups.
@article{borges_review_2014,
title = {Review of maintenance trials for major depressive disorder: a 25-year perspective from the {US} {Food} and {Drug} {Administration}.},
volume = {75},
issn = {1555-2101},
url = {https://www.psychiatrist.com/jcp/depression/review-maintenance-trials-major-depressive-disorder/},
doi = {10.4088/JCP.13r08722},
abstract = {The maintenance efficacy of antidepressants is usually assessed in postmarketing studies with a randomized withdrawal design. This report explores differences in relapse rates, trial characteristics, and success rates in maintenance efficacy studies submitted to the US Food and Drug Administration (FDA) over a 25-year period. Clinical data from all maintenance trials with antidepressants submitted to FDA between 1987 and 2012. Efficacy data were compiled from 15 maintenance clinical trials in adults diagnosed with major depressive disorder according to DSM-III or DSM-IV criteria. Trial characteristics, relapse rates, and time to relapse in each study were examined. Relapse rates were significantly lower (P {\textless} .05) in the drug arm than in the placebo arm in every study, with a mean relapse rate difference of 18\% and an average percent reduction in relapse rate of 52\% compared to placebo. Only 6\% of the relapse events occurred in the first 2 weeks of the double-blind phase. The separation between treatment arms continued to increase throughout the double-blind phase only in the trial with longest response stabilization period. Antidepressant maintenance trials have a high rate of success, indicating a benefit of continuing drug treatment after initial response to an antidepressant. This benefit appears to result mainly from a decreased rate of recurrent depression rather than from an effect of drug withdrawal in the placebo groups.},
number = {3},
journal = {The Journal of clinical psychiatry},
author = {Borges, Silvana and Chen, Yeh-Fong and Laughren, Thomas P and Temple, Robert and Patel, Hiren D and David, Paul A and Mathis, Mitchell and Unger, Ellis and Yang, Peiling and Khin, Ni A},
year = {2014},
pmid = {24717376},
keywords = {Adult, Depressive Disorder, Female, Humans, Major, Male, Middle Aged, Randomized Controlled Trials as Topic, Secondary Prevention, Time Factors, Treatment Outcome, United States, United States Food and Drug Administration, Withholding Treatment, drug therapy, prevention \& control, statistics \& numerical data},
pages = {205--214},
}2012 (5)
Flexible parametric joint modelling of longitudinal and survival data. Crowther, M. J., Abrams, K. R., & Lambert, P. C. Statistics in Medicine, 31(30):4456–4471, December, 2012.
doi abstract bibtex
doi abstract bibtex
The joint modelling of longitudinal and survival data is a highly active area of biostatistical research. The submodel for the longitudinal biomarker usually takes the form of a linear mixed effects model. We describe a flexible parametric approach for the survival submodel that models the log baseline cumulative hazard using restricted cubic splines. This approach overcomes limitations of standard parametric choices for the survival submodel, which can lack the flexibility to effectively capture the shape of the underlying hazard function. Numerical integration techniques, such as Gauss-Hermite quadrature, are usually required to evaluate both the cumulative hazard and the overall joint likelihood; however, by using a flexible parametric model, the cumulative hazard has an analytically tractable form, providing considerable computational benefits. We conduct an extensive simulation study to assess the proposed model, comparing it with a B-spline formulation, illustrating insensitivity of parameter estimates to the baseline cumulative hazard function specification. Furthermore, we compare non-adaptive and fully adaptive quadrature, showing the superiority of adaptive quadrature in evaluating the joint likelihood. We also describe a useful technique to simulate survival times from complex baseline hazard functions and illustrate the methods using an example data set investigating the association between longitudinal prothrombin index and survival of patients with liver cirrhosis, showing greater flexibility and improved stability with fewer parameters under the proposed model compared with the B-spline approach. We provide user-friendly Stata software.
@article{crowther_flexible_2012-1,
title = {Flexible parametric joint modelling of longitudinal and survival data},
volume = {31},
issn = {1097-0258},
doi = {10.1002/sim.5644},
abstract = {The joint modelling of longitudinal and survival data is a highly active area of biostatistical research. The submodel for the longitudinal biomarker usually takes the form of a linear mixed effects model. We describe a flexible parametric approach for the survival submodel that models the log baseline cumulative hazard using restricted cubic splines. This approach overcomes limitations of standard parametric choices for the survival submodel, which can lack the flexibility to effectively capture the shape of the underlying hazard function. Numerical integration techniques, such as Gauss-Hermite quadrature, are usually required to evaluate both the cumulative hazard and the overall joint likelihood; however, by using a flexible parametric model, the cumulative hazard has an analytically tractable form, providing considerable computational benefits. We conduct an extensive simulation study to assess the proposed model, comparing it with a B-spline formulation, illustrating insensitivity of parameter estimates to the baseline cumulative hazard function specification. Furthermore, we compare non-adaptive and fully adaptive quadrature, showing the superiority of adaptive quadrature in evaluating the joint likelihood. We also describe a useful technique to simulate survival times from complex baseline hazard functions and illustrate the methods using an example data set investigating the association between longitudinal prothrombin index and survival of patients with liver cirrhosis, showing greater flexibility and improved stability with fewer parameters under the proposed model compared with the B-spline approach. We provide user-friendly Stata software.},
language = {eng},
number = {30},
journal = {Statistics in Medicine},
author = {Crowther, M. J. and Abrams, K. R. and Lambert, P. C.},
month = dec,
year = {2012},
pmid = {23037571},
keywords = {Anti-Inflammatory Agents, Biomarkers, Biostatistics, Computer Simulation, Humans, Kaplan-Meier Estimate, Likelihood Functions, Linear Models, Liver Cirrhosis, Longitudinal Studies, Prednisone, Prognosis, Proportional Hazards Models, Randomized Controlled Trials as Topic, Time Factors},
pages = {4456--4471},
}An accumulator model for spontaneous neural activity prior to self-initiated movement. Schurger, A., Sitt, J. D, & Dehaene, S. Proceedings of the National Academy of Sciences of the United States of America, 109(42):E2904–13, October, 2012.
Paper doi abstract bibtex
Paper doi abstract bibtex A gradual buildup of neuronal activity known as the "readiness potential" reliably precedes voluntary self-initiated movements, in the average time locked to movement onset. This buildup is presumed to reflect the final stages of planning and preparation for movement. Here we present a different interpretation of the premovement buildup. We used a leaky stochastic accumulator to model the neural decision of "when" to move in a task where there is no specific temporal cue, but only a general imperative to produce a movement after an unspecified delay on the order of several seconds. According to our model, when the imperative to produce a movement is weak, the precise moment at which the decision threshold is crossed leading to movement is largely determined by spontaneous subthreshold fluctuations in neuronal activity. Time locking to movement onset ensures that these fluctuations appear in the average as a gradual exponential-looking increase in neuronal activity. Our model accounts for the behavioral and electroencephalography data recorded from human subjects performing the task and also makes a specific prediction that we confirmed in a second electroencephalography experiment: Fast responses to temporally unpredictable interruptions should be preceded by a slow negative-going voltage deflection beginning well before the interruption itself, even when the subject was not preparing to move at that particular moment.
@article{Schurger2012,
title = {An accumulator model for spontaneous neural activity prior to self-initiated movement.},
volume = {109},
issn = {1091-6490},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3479453&tool=pmcentrez&rendertype=abstract},
doi = {10.1073/pnas.1210467109},
abstract = {A gradual buildup of neuronal activity known as the "readiness potential" reliably precedes voluntary self-initiated movements, in the average time locked to movement onset. This buildup is presumed to reflect the final stages of planning and preparation for movement. Here we present a different interpretation of the premovement buildup. We used a leaky stochastic accumulator to model the neural decision of "when" to move in a task where there is no specific temporal cue, but only a general imperative to produce a movement after an unspecified delay on the order of several seconds. According to our model, when the imperative to produce a movement is weak, the precise moment at which the decision threshold is crossed leading to movement is largely determined by spontaneous subthreshold fluctuations in neuronal activity. Time locking to movement onset ensures that these fluctuations appear in the average as a gradual exponential-looking increase in neuronal activity. Our model accounts for the behavioral and electroencephalography data recorded from human subjects performing the task and also makes a specific prediction that we confirmed in a second electroencephalography experiment: Fast responses to temporally unpredictable interruptions should be preceded by a slow negative-going voltage deflection beginning well before the interruption itself, even when the subject was not preparing to move at that particular moment.},
number = {42},
urldate = {2015-12-06},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
author = {Schurger, Aaron and Sitt, Jacobo D and Dehaene, Stanislas},
month = oct,
year = {2012},
pmid = {22869750},
keywords = {Adult, Computer Simulation, Electroencephalography, Female, Humans, Male, Models, Movement, Movement: physiology, Neurological, Neurons, Neurons: physiology, Photic Stimulation, Psychomotor Performance, Psychomotor Performance: physiology, Stochastic Processes, Time Factors, readiness potential, spontaneous activity, spontaneous behaviour},
pages = {E2904--13},
}Deposition of brominated flame retardants to the Devon Ice Cap, Nunavut, Canada. Meyer, T., Muir, D. C G, Teixeira, C., Wang, X., Young, T., & Wania, F. Environmental science & technology, 46(2):826–33, January, 2012.
Paper doi abstract bibtex
Paper doi abstract bibtex Brominated flame retardants (BFRs) can be transported to Arctic regions via atmospheric long-range transport, however, relatively little is known about their deposition to terrestrial environments. Snow cores from the Devon Ice Cap in Nunavut, Canada served to determine the recent depositional trends of BFRs. Snow pits were dug in 2005, 2006, and 2008. Dating using annual snow accumulation data, ion chemistry, and density measurements established that the pits covered the period from approximately 1993 to spring 2008. Samples were extracted under clean room conditions, and analyzed using GC-negative ion MS for 26 tri- to decabromodiphenyl ethers (BDEs), as well as other BFRs, nonbrominated flame retardants, and industrial chemicals. Decabromodiphenyl ether (BDE-209) was the major congener present in all samples followed by nona-BDEs (BDE-207, BDE-206, and BDE-208), both accounting for 89% and 7% of total BDE, respectively. BDE-209 concentrations were in most cases significantly correlated (P \textless 0.05) to tri- to nona-BDE homologues, and the strength of the correlations increased with increasing degree of bromination. Prior to or after deposition BDE-209 may be subject to debromination to lighter congeners. Deposition fluxes of BDE-209 show no clear temporal trend and range between 90 and 2000 pg·cm(-2)·year(-1). Back trajectory origin in densely populated areas of northeastern North America is significantly correlated (P \textless 0.005) with the BDE-209 deposition flux. Several other high production volume and/or alternative BFRs such as hexabromocyclododecane (HBCD), 1,2-bis(2,4,6-dibromophenoxy)ethane (BTBPE), pentabromo ethyl benzene (PBEBz), and pentabromobenzene (PBBz), as well as the industrial chemical 1,3,5-tribromobenzene (135-TBBz) were found consistently in the snow pits.
@article{meyer_deposition_2012,
title = {Deposition of brominated flame retardants to the {Devon} {Ice} {Cap}, {Nunavut}, {Canada}.},
volume = {46},
issn = {1520-5851},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22148267},
doi = {10.1021/es202900u},
abstract = {Brominated flame retardants (BFRs) can be transported to Arctic regions via atmospheric long-range transport, however, relatively little is known about their deposition to terrestrial environments. Snow cores from the Devon Ice Cap in Nunavut, Canada served to determine the recent depositional trends of BFRs. Snow pits were dug in 2005, 2006, and 2008. Dating using annual snow accumulation data, ion chemistry, and density measurements established that the pits covered the period from approximately 1993 to spring 2008. Samples were extracted under clean room conditions, and analyzed using GC-negative ion MS for 26 tri- to decabromodiphenyl ethers (BDEs), as well as other BFRs, nonbrominated flame retardants, and industrial chemicals. Decabromodiphenyl ether (BDE-209) was the major congener present in all samples followed by nona-BDEs (BDE-207, BDE-206, and BDE-208), both accounting for 89\% and 7\% of total BDE, respectively. BDE-209 concentrations were in most cases significantly correlated (P {\textbackslash}textless 0.05) to tri- to nona-BDE homologues, and the strength of the correlations increased with increasing degree of bromination. Prior to or after deposition BDE-209 may be subject to debromination to lighter congeners. Deposition fluxes of BDE-209 show no clear temporal trend and range between 90 and 2000 pg·cm(-2)·year(-1). Back trajectory origin in densely populated areas of northeastern North America is significantly correlated (P {\textbackslash}textless 0.005) with the BDE-209 deposition flux. Several other high production volume and/or alternative BFRs such as hexabromocyclododecane (HBCD), 1,2-bis(2,4,6-dibromophenoxy)ethane (BTBPE), pentabromo ethyl benzene (PBEBz), and pentabromobenzene (PBBz), as well as the industrial chemical 1,3,5-tribromobenzene (135-TBBz) were found consistently in the snow pits.},
number = {2},
journal = {Environmental science \& technology},
author = {Meyer, Torsten and Muir, Derek C G and Teixeira, Camilla and Wang, Xiaowa and Young, Teresa and Wania, Frank},
month = jan,
year = {2012},
pmid = {22148267},
keywords = {Arctic Regions, Brominated, Brominated: chemistry, Canada, Environmental Monitoring, Environmental Pollutants, Environmental Pollutants: chemistry, Flame Retardants: analysis, Flame retardants, Hydrocarbons, Ice, Ice: analysis, Time Factors},
pages = {826--33},
}Emergency Medical Services Response Time and Mortality in an Urban Setting. Blanchard, I. E., Doig, C. J., Hagel, B. E., Anton, A. R., Zygun, D. A., Kortbeek, J. B., Powell, D. G., Williamson, T. S., Fick, G. H., & Innes, G. D. Prehospital Emergency Care, 16(1):142--151, January, 2012.
Paper doi abstract bibtex
Paper doi abstract bibtex Background. A common tenet in emergency medical services (EMS) is that faster response equates to better patient outcome, translated by some EMS operations into a goal of a response time of 8 minutes or less for advanced life support (ALS) units responding to life-threatening events. Objective. To explore whether an 8-minute EMS response time was associated with mortality. Methods. This was a one-year retrospective cohort study of adults with a life-threatening event as assessed at the time of the 9-1-1 call (Medical Priority Dispatch System Echo- or Delta-level event). The study setting was an urban all-ALS EMS system serving a population of approximately 1 million. Response time was defined as 9-1-1 call receipt to ALS unit arrival on scene, and outcome was defined as all-cause mortality at hospital discharge. Potential covariates included patient acuity, age, gender, and combined scene and transport interval time. Stratified analysis and logistic regression were used to assess the response time–mortality association. Results. There were 7,760 unit responses that met the inclusion criteria; 1,865 (24%) were ≥8 minutes. The average patient age was 56.7 years (standard deviation = 21.5). For patients with a response time ≥8 minutes, 7.1% died, compared with 6.4% for patients with a response time ≤7 minutes 59 seconds (risk difference 0.7%; 95% confidence interval [CI]: –0.5%, 2.0%). The adjusted odds ratio of mortality for ≥8 minutes was 1.19 (95% CI: 0.97, 1.47). An exploratory analysis suggested there may be a small beneficial effect of response ≤7 minutes 59 seconds for those who survived to become an inpatient (adjusted odds ratio = 1.30; 95% CI: 1.00, 1.69). Conclusions. These results call into question the clinical effectiveness of a dichotomous 8-minute ALS response time on decreasing mortality for the majority of adult patients identified as having a life-threatening event at the time of the 9-1-1 call. However, this study does not suggest that rapid EMS response is undesirable or unimportant for certain patients. This analysis highlights the need for further research on who may benefit from rapid EMS response, whether these individuals can be identified at the time of the 9-1-1 call, and what the optimum response time is.
@article{blanchard_emergency_2012,
title = {Emergency {Medical} {Services} {Response} {Time} and {Mortality} in an {Urban} {Setting}},
volume = {16},
issn = {1090-3127},
url = {http://dx.doi.org/10.3109/10903127.2011.614046},
doi = {10.3109/10903127.2011.614046},
abstract = {Background. A common tenet in emergency medical services (EMS) is that faster response equates to better patient outcome, translated by some EMS operations into a goal of a response time of 8 minutes or less for advanced life support (ALS) units responding to life-threatening events. Objective. To explore whether an 8-minute EMS response time was associated with mortality. Methods. This was a one-year retrospective cohort study of adults with a life-threatening event as assessed at the time of the 9-1-1 call (Medical Priority Dispatch System Echo- or Delta-level event). The study setting was an urban all-ALS EMS system serving a population of approximately 1 million. Response time was defined as 9-1-1 call receipt to ALS unit arrival on scene, and outcome was defined as all-cause mortality at hospital discharge. Potential covariates included patient acuity, age, gender, and combined scene and transport interval time. Stratified analysis and logistic regression were used to assess the response time–mortality association. Results. There were 7,760 unit responses that met the inclusion criteria; 1,865 (24\%) were ≥8 minutes. The average patient age was 56.7 years (standard deviation = 21.5). For patients with a response time ≥8 minutes, 7.1\% died, compared with 6.4\% for patients with a response time ≤7 minutes 59 seconds (risk difference 0.7\%; 95\% confidence interval [CI]: –0.5\%, 2.0\%). The adjusted odds ratio of mortality for ≥8 minutes was 1.19 (95\% CI: 0.97, 1.47). An exploratory analysis suggested there may be a small beneficial effect of response ≤7 minutes 59 seconds for those who survived to become an inpatient (adjusted odds ratio = 1.30; 95\% CI: 1.00, 1.69). Conclusions. These results call into question the clinical effectiveness of a dichotomous 8-minute ALS response time on decreasing mortality for the majority of adult patients identified as having a life-threatening event at the time of the 9-1-1 call. However, this study does not suggest that rapid EMS response is undesirable or unimportant for certain patients. This analysis highlights the need for further research on who may benefit from rapid EMS response, whether these individuals can be identified at the time of the 9-1-1 call, and what the optimum response time is.},
number = {1},
journal = {Prehospital Emergency Care},
author = {Blanchard, Ian E. and Doig, Christopher J. and Hagel, Brent E. and Anton, Andrew R. and Zygun, David A. and Kortbeek, John B. and Powell, D. Gregory and Williamson, Tyler S. and Fick, Gordon H. and Innes, Grant D.},
month = jan,
year = {2012},
pmid = {22026820},
keywords = {Emergency Medical Services, Mortality, Time Factors, ambulance, outcome assessment, response},
pages = {142--151}
}Cartilage and bone markers and inflammatory cytokines are increased in synovial fluid in the acute phase of knee injury (hemarthrosis) - A cross-sectional analysis. Swärd, P., Frobell, R., Englund, M., Roos, H., & Struglics, A. Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society, 20(11):1302–1308, November, 2012.
Paper doi abstract bibtex
Paper doi abstract bibtex PURPOSE: The aim of this cross-sectional study was to investigate concentrations of cartilage and bone markers, and pro-inflammatory cytokines in synovial fluid (SF) collected at different time-points from acutely injured knees with hemarthrosis and to compare these with SF concentrations of knees of age and gender-matched healthy reference subjects. METHODS: SF was aspirated from the acutely injured knee of 111 individuals (mean age 27 years, span 13-64 years, 22% women). Concentrations of sulfated glycosaminoglycan (sGAG) were measured by Alcian blue precipitation whereas cartilage ARGS, bone biomarkers [osteocalcin (OCL), secreted protein acidic and rich in cysteine (SPARC) and osteopontin (OPN)] and pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α] were analyzed using electrochemiluminescence. Samples were also analyzed with regard to time between injury and aspiration [same day (n = 29), 1 day (n = 31), 2-3 days (n = 19), 4-7 days (n = 20) and 8-23 days (n = 12)]. RESULTS: SF concentrations of ARGS (P \textless 0.001), SPARC (P \textless 0.001), OPN (P \textless 0.001), and all cytokines (P \textless 0.001), but not sGAG (P = 0.06) or OCL (P = 0.992), were significantly higher in injured knees compared to knees of reference subjects. The cartilage markers sGAG and ARGS were significantly higher in knees aspirated later than 1 day after injury, whereas concentrations of SPARC and OPN and all cytokines were higher in knees aspirated the same day as the injury and at all time-points thereafter. CONCLUSIONS: Our results suggest that an acute knee injury is associated with an instant local biochemical response to the trauma, which may affect cartilage and bone as well as the inflammatory activity.
@article{sward_cartilage_2012,
title = {Cartilage and bone markers and inflammatory cytokines are increased in synovial fluid in the acute phase of knee injury (hemarthrosis) - {A} cross-sectional analysis.},
volume = {20},
issn = {1522-9653},
url = {http://dx.doi.org/10.1016%2Fj.joca.2012.07.021},
doi = {10.1016/j.joca.2012.07.021},
abstract = {PURPOSE: The aim of this cross-sectional study was to investigate concentrations of cartilage and bone markers, and pro-inflammatory cytokines in synovial fluid (SF) collected at different time-points from acutely injured knees with hemarthrosis and to compare these with SF concentrations of knees of age and gender-matched healthy reference subjects.
METHODS: SF was aspirated from the acutely injured knee of 111 individuals (mean age 27 years, span 13-64 years, 22\% women). Concentrations of sulfated glycosaminoglycan (sGAG) were measured by Alcian blue precipitation whereas cartilage ARGS, bone biomarkers [osteocalcin (OCL), secreted protein acidic and rich in cysteine (SPARC) and osteopontin (OPN)] and pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α] were analyzed using electrochemiluminescence. Samples were also analyzed with regard to time between injury and aspiration [same day (n = 29), 1 day (n = 31), 2-3 days (n = 19), 4-7 days (n = 20) and 8-23 days (n = 12)].
RESULTS: SF concentrations of ARGS (P {\textless} 0.001), SPARC (P {\textless} 0.001), OPN (P {\textless} 0.001), and all cytokines (P {\textless} 0.001), but not sGAG (P = 0.06) or OCL (P = 0.992), were significantly higher in injured knees compared to knees of reference subjects. The cartilage markers sGAG and ARGS were significantly higher in knees aspirated later than 1 day after injury, whereas concentrations of SPARC and OPN and all cytokines were higher in knees aspirated the same day as the injury and at all time-points thereafter.
CONCLUSIONS: Our results suggest that an acute knee injury is associated with an instant local biochemical response to the trauma, which may affect cartilage and bone as well as the inflammatory activity.},
language = {eng},
number = {11},
journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society},
author = {Swärd, P. and Frobell, R. and Englund, M. and Roos, H. and Struglics, A.},
month = nov,
year = {2012},
pmid = {22874525},
keywords = {Acute Disease, Adolescent, Adult, Aggrecans, Biomarkers, Bone and Bones, Cartilage, Articular, Cross-Sectional Studies, Cytokines, Female, Hemarthrosis, Humans, Knee Injuries, Male, Middle Aged, Synovial Fluid, Time Factors, Young Adult},
pages = {1302--1308},
}2011 (8)
Self-help parenting interventions for childhood behaviour disorders: a review of the evidence. O'Brien, M & Daley, D Child: care, health and development, 37(5):623–37, September, 2011.
Paper doi abstract bibtex
Paper doi abstract bibtex The use of self-help interventions for parents of children with behaviour problems is becoming more prevalent. This review critically evaluated the evidence supporting the efficacy of such programmes for children with behaviour problems. Using a systematic literature search, two modes of delivery were evaluated, namely bibliotherapy and multimedia. Programmes that included minimal therapist support were also included. Overall, there is good evidence supporting the efficacy of self-help programmes in improving child behaviour, over the short and longer term. Self-help programmes led to outcomes similar to those achieved with more intensive therapist input. Including minimal levels of therapist support in addition to self-help materials enhances child and parent outcomes. Parents view self-help favourably but significantly less so than programmes including some form of therapist input. The future directions for self-help parent programmes include the need for longer-term follow-ups, the identification of moderators of outcome and economic evaluations of self-help programmes.
@article{obrien_self-help_2011,
title = {Self-help parenting interventions for childhood behaviour disorders: a review of the evidence.},
volume = {37},
issn = {1365-2214},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21585419},
doi = {10.1111/j.1365-2214.2011.01231.x},
abstract = {The use of self-help interventions for parents of children with behaviour problems is becoming more prevalent. This review critically evaluated the evidence supporting the efficacy of such programmes for children with behaviour problems. Using a systematic literature search, two modes of delivery were evaluated, namely bibliotherapy and multimedia. Programmes that included minimal therapist support were also included. Overall, there is good evidence supporting the efficacy of self-help programmes in improving child behaviour, over the short and longer term. Self-help programmes led to outcomes similar to those achieved with more intensive therapist input. Including minimal levels of therapist support in addition to self-help materials enhances child and parent outcomes. Parents view self-help favourably but significantly less so than programmes including some form of therapist input. The future directions for self-help parent programmes include the need for longer-term follow-ups, the identification of moderators of outcome and economic evaluations of self-help programmes.},
number = {5},
urldate = {2012-07-16},
journal = {Child: care, health and development},
author = {O'Brien, M and Daley, D},
month = sep,
year = {2011},
pmid = {21585419},
keywords = {Adolescent, Child, Child Behavior Disorders, Child Behavior Disorders: prevention \& control, Child Behavior Disorders: therapy, Cost-Benefit Analysis, Humans, Parenting, Parenting: psychology, Program Evaluation, Programmed Instruction as Topic, Programmed Instruction as Topic: economics, Psychotherapy, Group, Self Concept, Time Factors},
pages = {623--37},
}High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array. Tung, Y., Hsiao, A., Y., Allen, S., G., Torisawa, Y., Ho, M., & Takayama, S. The Analyst, 136(3):473-8, The Royal Society of Chemistry, 2, 2011.
Website abstract bibtex
Website abstract bibtex Culture of cells as three-dimensional (3D) aggregates can enhance in vitro tests for basic biological research as well as for therapeutics development. Such 3D culture models, however, are often more complicated, cumbersome, and expensive than two-dimensional (2D) cultures. This paper describes a 384-well format hanging drop culture plate that makes spheroid formation, culture, and subsequent drug testing on the obtained 3D cellular constructs as straightforward to perform and adapt to existing high-throughput screening (HTS) instruments as conventional 2D cultures. Using this platform, we show that drugs with different modes of action produce distinct responses in the physiological 3D cell spheroids compared to conventional 2D cell monolayers. Specifically, the anticancer drug 5-fluorouracil (5-FU) has higher anti-proliferative effects on 2D cultures whereas the hypoxia activated drug commonly referred to as tirapazamine (TPZ) are more effective against 3D cultures. The multiplexed 3D hanging drop culture and testing plate provides an efficient way to obtain biological insights that are often lost in 2D platforms.
@article{
title = {High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array.},
type = {article},
year = {2011},
identifiers = {[object Object]},
keywords = {Antineoplastic Agents,Antineoplastic Agents: pharmacology,Cell Culture Techniques,Cell Culture Techniques: instrumentation,Cell Culture Techniques: methods,Cell Line,Cell Survival,Cell Survival: drug effects,Cellular,Cellular: cytology,Cellular: drug effects,Drug Evaluation,High-Throughput Screening Assays,High-Throughput Screening Assays: instrumentation,High-Throughput Screening Assays: methods,Humans,Osmolar Concentration,Preclinical,Preclinical: instrumentation,Preclinical: methods,Spheroids,Time Factors,Tumor},
pages = {473-8},
volume = {136},
websites = {http://pubs.rsc.org/en/content/articlehtml/2011/an/c0an00609b},
month = {2},
publisher = {The Royal Society of Chemistry},
day = {7},
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abstract = {Culture of cells as three-dimensional (3D) aggregates can enhance in vitro tests for basic biological research as well as for therapeutics development. Such 3D culture models, however, are often more complicated, cumbersome, and expensive than two-dimensional (2D) cultures. This paper describes a 384-well format hanging drop culture plate that makes spheroid formation, culture, and subsequent drug testing on the obtained 3D cellular constructs as straightforward to perform and adapt to existing high-throughput screening (HTS) instruments as conventional 2D cultures. Using this platform, we show that drugs with different modes of action produce distinct responses in the physiological 3D cell spheroids compared to conventional 2D cell monolayers. Specifically, the anticancer drug 5-fluorouracil (5-FU) has higher anti-proliferative effects on 2D cultures whereas the hypoxia activated drug commonly referred to as tirapazamine (TPZ) are more effective against 3D cultures. The multiplexed 3D hanging drop culture and testing plate provides an efficient way to obtain biological insights that are often lost in 2D platforms.},
bibtype = {article},
author = {Tung, Yi-Chung and Hsiao, Amy Y and Allen, Steven G and Torisawa, Yu-suke and Ho, Mitchell and Takayama, Shuichi},
journal = {The Analyst},
number = {3}
}Comparison of the results of Cox proportional hazards model and parametric models in the study of length of stay in a tertiary teaching hospital in Tehran, Iran. Ravangard, R., Arab, M., Rashidian, A., Akbarisari, A., Zare, A., & Zeraati, H. Acta medica Iranica, 49(10):650–658, 2011.
abstract bibtex
abstract bibtex
Survival analysis is a set of methods used for analysis of the data which exist until the occurrence of an event. This study aimed to compare the results of the use of the semi-parametric Cox model with parametric models to determine the factors influencing the length of stay of patients in the inpatient units of Women Hospital in Tehran, Iran. In this historical cohort study all 3421 charts of the patients admitted to Obstetrics, Surgery and Oncology units in 2008 were reviewed and the required patient data such as medical insurance coverage types, admission months, days and times, inpatient units, final diagnoses, the number of diagnostic tests, admission types were collected. The patient length of stay in hospital 'leading to recovery' was considered as a survival variable. To compare the semi-parametric Cox model and parametric (including exponential, Weibull, Gompertz, log-normal, log-logistic and gamma) models and find the best model fitted to studied data, Akaike's Information Criterion (AIC) and Cox-Snell residual were used. P\textless0.05 was considered as statistically significant. AIC and Cox-Snell residual graph showed that the gamma model had the lowest AIC (4288.598) and the closest graph to the bisector. The results of the gamma model showed that factors affecting the patient length of stay were admission day, inpatient unit, related physician specialty, emergent admission, final diagnosis and the number of laboratory tests, radiographies and sonographies (P\textless0.05). The results showed that the gamma model provided a better fit to the studied data than the Cox proportional hazards model. Therefore, it is better for researchers of healthcare field to consider this model in their researches about the patient length of stay (LOS) if the assumption of proportional hazards is not fulfilled.
@article{ravangard_comparison_2011,
title = {Comparison of the results of {Cox} proportional hazards model and parametric models in the study of length of stay in a tertiary teaching hospital in {Tehran}, {Iran}},
volume = {49},
issn = {1735-9694},
abstract = {Survival analysis is a set of methods used for analysis of the data which exist until the occurrence of an event. This study aimed to compare the results of the use of the semi-parametric Cox model with parametric models to determine the factors influencing the length of stay of patients in the inpatient units of Women Hospital in Tehran, Iran. In this historical cohort study all 3421 charts of the patients admitted to Obstetrics, Surgery and Oncology units in 2008 were reviewed and the required patient data such as medical insurance coverage types, admission months, days and times, inpatient units, final diagnoses, the number of diagnostic tests, admission types were collected. The patient length of stay in hospital 'leading to recovery' was considered as a survival variable. To compare the semi-parametric Cox model and parametric (including exponential, Weibull, Gompertz, log-normal, log-logistic and gamma) models and find the best model fitted to studied data, Akaike's Information Criterion (AIC) and Cox-Snell residual were used. P{\textless}0.05 was considered as statistically significant. AIC and Cox-Snell residual graph showed that the gamma model had the lowest AIC (4288.598) and the closest graph to the bisector. The results of the gamma model showed that factors affecting the patient length of stay were admission day, inpatient unit, related physician specialty, emergent admission, final diagnosis and the number of laboratory tests, radiographies and sonographies (P{\textless}0.05). The results showed that the gamma model provided a better fit to the studied data than the Cox proportional hazards model. Therefore, it is better for researchers of healthcare field to consider this model in their researches about the patient length of stay (LOS) if the assumption of proportional hazards is not fulfilled.},
language = {eng},
number = {10},
journal = {Acta medica Iranica},
author = {Ravangard, Ramin and Arab, Mohamad and Rashidian, Arash and Akbarisari, Ali and Zare, Ali and Zeraati, Hojjat},
year = {2011},
pmid = {22071639},
keywords = {Data Interpretation, Statistical, Female, Health Services Research, Hospitals, Teaching, Humans, Iran, Length of Stay, Proportional Hazards Models, Risk Assessment, Risk Factors, Survival Analysis, Survival Rate, Time Factors, Women's Health Services},
pages = {650--658}
}Effects of the construction of Scroby Sands offshore wind farm on the prey base of Little tern Sternula albifrons at its most important UK colony. Perrow, M., R., Gilroy, J., J., Skeate, E., R., & Tomlinson, M., L. Marine Pollution Bulletin, 62(8):1661-70, Elsevier Ltd, 8, 2011.
abstract bibtex
abstract bibtex
Despite widespread interest in the impacts of wind farms upon birds, few researchers have examined the potential for indirect or trophic (predator-prey) effects. Using surface trawls, we monitored prey abundance before and after construction of a 30 turbine offshore wind farm sited close to an internationally important colony of Little terns. Observations confirmed that young-of-the-year clupeids dominated chick diet, which trawl samples suggested were mainly herring. Multivariate modelling indicated a significant reduction in herring abundance from 2004 onwards that could not be explained by environmental factors. Intensely noisy monopile installation during the winter spawning period was suggested to be responsible. Reduced prey abundance corresponded with a significant decline in Little tern foraging success. Unprecedented egg abandonment and lack of chick hatching tentatively suggested a colony-scale response in some years. We urge a precautionary approach to the timing and duration of pile-driving activity supported with long-term targeted monitoring of sensitive receptors.
@article{
title = {Effects of the construction of Scroby Sands offshore wind farm on the prey base of Little tern Sternula albifrons at its most important UK colony},
type = {article},
year = {2011},
identifiers = {[object Object]},
keywords = {Animals,Charadriiformes,Charadriiformes: classification,Charadriiformes: growth & development,Charadriiformes: physiology,Energy-Generating Resources,Environmental Exposure,Environmental Exposure: analysis,Environmental Monitoring,Environmental Pollutants,Environmental Pollutants: toxicity,Fisheries,Food Chain,Great Britain,Time Factors,Wind},
pages = {1661-70},
volume = {62},
month = {8},
publisher = {Elsevier Ltd},
id = {4715ad60-aba9-3fdc-94bb-89262731120f},
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abstract = {Despite widespread interest in the impacts of wind farms upon birds, few researchers have examined the potential for indirect or trophic (predator-prey) effects. Using surface trawls, we monitored prey abundance before and after construction of a 30 turbine offshore wind farm sited close to an internationally important colony of Little terns. Observations confirmed that young-of-the-year clupeids dominated chick diet, which trawl samples suggested were mainly herring. Multivariate modelling indicated a significant reduction in herring abundance from 2004 onwards that could not be explained by environmental factors. Intensely noisy monopile installation during the winter spawning period was suggested to be responsible. Reduced prey abundance corresponded with a significant decline in Little tern foraging success. Unprecedented egg abandonment and lack of chick hatching tentatively suggested a colony-scale response in some years. We urge a precautionary approach to the timing and duration of pile-driving activity supported with long-term targeted monitoring of sensitive receptors.},
bibtype = {article},
author = {Perrow, Martin R and Gilroy, James J and Skeate, Eleanor R and Tomlinson, Mark L},
journal = {Marine Pollution Bulletin},
number = {8}
}Natural history of radiographic hip osteoarthritis: A retrospective cohort study with 11-28 years of followup. Franklin, J., Ingvarsson, T., Englund, M., Ingimarsson, O., Robertsson, O., & Lohmander, L. S. Arthritis care & research, 63(5):689–695, May, 2011.
Paper doi abstract bibtex
Paper doi abstract bibtex OBJECTIVE: To evaluate the association between radiographic hip osteoarthritis (OA) and future total hip replacement (THR) due to OA or hip fracture. METHODS: We studied a cohort of individuals who had colon radiography from 1980-1997. Minimal joint space (MJS) was measured and each hip was graded for radiographic OA according to the Kellgren/Lawrence scale. Subjects were followed until the end of 2008. A Cox proportional hazards model, adjusted for age and sex, was used to evaluate factors associated with THR and hip fracture. RESULTS: A total of 2,953 hips were studied (57% women). The cumulative incidence of THR was 2.5% and the cumulative incidence of hip fracture was 2.6%. For hips with radiographic hip OA (MJS of 2.5 mm or less), the cumulative incidence of THR was 16.9% and the hazard ratio (HR) for THR was 13.2 (95% confidence interval [95% CI] 8.1-21). Using Kellgren/Lawrence grading, the HR for THR was 12.9 (95% CI 7.9-21) for hips with radiographic OA compared to those without. The HR for all types of hip fracture for hips with radiographic OA (MJS of 2.5 mm or less) was 0.47 (95% CI 0.15-1.5), for intracapsular fractures was 0.29 (95% CI 0.04-2.1), and for extracapsular fractures was 0.67 (95% CI 0.16-2.8). CONCLUSION: The risk of THR due to OA is substantially increased in patients with radiographic hip OA, regardless of symptoms, and increases with decreasing MJS. However, 11-28 years after having had radiographic hip OA, more than 4 of 5 of those having radiographic signs of hip OA had not had a THR for OA.
@article{franklin_natural_2011,
title = {Natural history of radiographic hip osteoarthritis: {A} retrospective cohort study with 11-28 years of followup.},
volume = {63},
copyright = {Copyright (c) 2011 by the American College of Rheumatology.},
issn = {2151-4658 2151-464X},
url = {http://dx.doi.org/10.1002%2Facr.20412},
doi = {10.1002/acr.20412},
abstract = {OBJECTIVE: To evaluate the association between radiographic hip osteoarthritis (OA) and future total hip replacement (THR) due to OA or hip fracture. METHODS: We studied a cohort of individuals who had colon radiography from 1980-1997. Minimal joint space (MJS) was measured and each hip was graded for radiographic OA according to the Kellgren/Lawrence scale. Subjects were followed until the end of 2008. A Cox proportional hazards model, adjusted for age and sex, was used to evaluate factors associated with THR and hip fracture. RESULTS: A total of 2,953 hips were studied (57\% women). The cumulative incidence of THR was 2.5\% and the cumulative incidence of hip fracture was 2.6\%. For hips with radiographic hip OA (MJS of 2.5 mm or less), the cumulative incidence of THR was 16.9\% and the hazard ratio (HR) for THR was 13.2 (95\% confidence interval [95\% CI] 8.1-21). Using Kellgren/Lawrence grading, the HR for THR was 12.9 (95\% CI 7.9-21) for hips with radiographic OA compared to those without. The HR for all types of hip fracture for hips with radiographic OA (MJS of 2.5 mm or less) was 0.47 (95\% CI 0.15-1.5), for intracapsular fractures was 0.29 (95\% CI 0.04-2.1), and for extracapsular fractures was 0.67 (95\% CI 0.16-2.8). CONCLUSION: The risk of THR due to OA is substantially increased in patients with radiographic hip OA, regardless of symptoms, and increases with decreasing MJS. However, 11-28 years after having had radiographic hip OA, more than 4 of 5 of those having radiographic signs of hip OA had not had a THR for OA.},
language = {eng},
number = {5},
journal = {Arthritis care \& research},
author = {Franklin, Jonas and Ingvarsson, Thorvaldur and Englund, Martin and Ingimarsson, Olafur and Robertsson, Otto and Lohmander, L. Stefan},
month = may,
year = {2011},
pmid = {21557524},
keywords = {Adult, Aged, Aged, 80 and over, Arthroplasty, Replacement, Hip, Disease Progression, Female, Follow-Up Studies, Hip Fractures/etiology/radiography/surgery, Hip Joint/*radiography, Humans, Iceland, Male, Middle Aged, Osteoarthritis, Hip/complications/*radiography/surgery, Predictive Value of Tests, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Risk Factors, Severity of Illness Index, Time Factors},
pages = {689--695},
}Spatial gradients and multidimensional dynamics in a neural integrator circuit. Miri, A., Daie, K., Arrenberg, A. B, Baier, H., Aksay, E., & Tank, D. W Nature neuroscience, 14(9):1150–9, September, 2011.
Paper doi abstract bibtex
Paper doi abstract bibtex In a neural integrator, the variability and topographical organization of neuronal firing-rate persistence can provide information about the circuit's functional architecture. We used optical recording to measure the time constant of decay of persistent firing (persistence time) across a population of neurons comprising the larval zebrafish oculomotor velocity-to-position neural integrator. We found extensive persistence time variation (tenfold; coefficients of variation = 0.58-1.20) across cells in individual larvae. We also found that the similarity in firing between two neurons decreased as the distance between them increased and that a gradient in persistence time was mapped along the rostrocaudal and dorsoventral axes. This topography is consistent with the emergence of persistence time heterogeneity from a circuit architecture in which nearby neurons are more strongly interconnected than distant ones. Integrator circuit models characterized by multiple dimensions of slow firing-rate dynamics can account for our results.
@article{Miri2011,
title = {Spatial gradients and multidimensional dynamics in a neural integrator circuit.},
volume = {14},
issn = {1546-1726},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21857656},
doi = {10.1038/nn.2888},
abstract = {In a neural integrator, the variability and topographical organization of neuronal firing-rate persistence can provide information about the circuit's functional architecture. We used optical recording to measure the time constant of decay of persistent firing (persistence time) across a population of neurons comprising the larval zebrafish oculomotor velocity-to-position neural integrator. We found extensive persistence time variation (tenfold; coefficients of variation = 0.58-1.20) across cells in individual larvae. We also found that the similarity in firing between two neurons decreased as the distance between them increased and that a gradient in persistence time was mapped along the rostrocaudal and dorsoventral axes. This topography is consistent with the emergence of persistence time heterogeneity from a circuit architecture in which nearby neurons are more strongly interconnected than distant ones. Integrator circuit models characterized by multiple dimensions of slow firing-rate dynamics can account for our results.},
number = {9},
urldate = {2012-07-25},
journal = {Nature neuroscience},
author = {Miri, Andrew and Daie, Kayvon and Arrenberg, Aristides B and Baier, Herwig and Aksay, Emre and Tank, David W},
month = sep,
year = {2011},
pmid = {21857656},
keywords = {\#nosource, Action Potentials, Animals, Animals, Genetically Modified, Brain Stem, Brain Stem: cytology, Calcium, Calcium: metabolism, Computer Simulation, Eye Movements, Eye Movements: genetics, Eye Movements: physiology, Functional Laterality, Gene Expression Regulation, Gene Expression Regulation: genetics, Gene Expression Regulation: physiology, Larva, Light, Microphthalmia-Associated Transcription Factor, Microphthalmia-Associated Transcription Factor: de, Models, Neurological, Nerve Net, Nerve Net: physiology, Neurons, Neurons: physiology, Nonlinear Dynamics, Photic Stimulation, Photic Stimulation: methods, Time Factors, Zebrafish, Zebrafish Proteins, Zebrafish Proteins: deficiency, Zebrafish Proteins: genetics, mae},
pages = {1150--9},
}Risks of stroke and mortality associated with suboptimal anticoagulation in atrial fibrillation patients. Gallagher, A. M., Setakis, E., Plumb, J. M., Clemens, A., & van Staa, T. Thrombosis and Haemostasis, 106(5):968--977, November, 2011.
doi abstract bibtex
doi abstract bibtex
Atrial fibrillation (AF) carries an increased risk of ischaemic stroke, and oral anticoagulation with warfarin can reduce this risk. The objective of this study was to evaluate the association between time in therapeutic International Normalised Ratio (INR) range when receiving warfarin and the risk of stroke and mortality. The study cohort included AF patients aged 40 years and older included in the UK General Practice Research Database. For patients treated with warfarin we computed the percentage of follow-up time spent within therapeutic range. Cox regression was used to assess the association between INR and outcomes while controlling for patient demographics, health status and concomitant medication. The study population included 27,458 warfarin-treated (with at least 3 INR measurements) and 10,449 patients not treated with antithrombotic therapy. Overall the warfarin users spent 63% of their time within therapeutic range (TTR). This percentage did not vary substantially by age, sex and CHA2DS2-VASc score. Patients who spent at least 70% of time within therapeutic range had a 79% reduced risk of stroke compared to patients with ≤30% of time in range (adjusted relative rate of 0.21; 95% confidence interval 0.18-0.25). Mortality rates were also significantly lower with at least 70% of time spent within therapeutic range. In conclusion, good anticoagulation control was associated with a reduction in the risk of stroke.
@article{gallagher_risks_2011,
title = {Risks of stroke and mortality associated with suboptimal anticoagulation in atrial fibrillation patients},
volume = {106},
issn = {0340-6245},
doi = {10.1160/TH11-05-0353},
abstract = {Atrial fibrillation (AF) carries an increased risk of ischaemic stroke, and oral anticoagulation with warfarin can reduce this risk. The objective of this study was to evaluate the association between time in therapeutic International Normalised Ratio (INR) range when receiving warfarin and the risk of stroke and mortality. The study cohort included AF patients aged 40 years and older included in the UK General Practice Research Database. For patients treated with warfarin we computed the percentage of follow-up time spent within therapeutic range. Cox regression was used to assess the association between INR and outcomes while controlling for patient demographics, health status and concomitant medication. The study population included 27,458 warfarin-treated (with at least 3 INR measurements) and 10,449 patients not treated with antithrombotic therapy. Overall the warfarin users spent 63\% of their time within therapeutic range (TTR). This percentage did not vary substantially by age, sex and CHA2DS2-VASc score. Patients who spent at least 70\% of time within therapeutic range had a 79\% reduced risk of stroke compared to patients with ≤30\% of time in range (adjusted relative rate of 0.21; 95\% confidence interval 0.18-0.25). Mortality rates were also significantly lower with at least 70\% of time spent within therapeutic range. In conclusion, good anticoagulation control was associated with a reduction in the risk of stroke.},
language = {eng},
number = {5},
journal = {Thrombosis and Haemostasis},
author = {Gallagher, A. M. and Setakis, E. and Plumb, J. M. and Clemens, A. and van Staa, T.-P.},
month = nov,
year = {2011},
pmid = {21901239},
keywords = {Adult, Aged, Aged, 80 and over, Anticoagulants, Atrial Fibrillation, Blood Coagulation, Drug Monitoring, Female, General Practice, Great Britain, Humans, International Normalized Ratio, Kaplan-Meier Estimate, Male, Middle Aged, Odds Ratio, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Warfarin, databases as topic, stroke},
pages = {968--977}
}Long-term use of fluticasone propionate/salmeterol fixed-dose combination and incidence of cataracts and glaucoma among chronic obstructive pulmonary disease patients in the UK General Practice Research Database. Miller, D. P., Watkins, S. E., Sampson, T., & Davis, K. J. International Journal of Chronic Obstructive Pulmonary Disease, 6:467--476, 2011.
doi abstract bibtex
doi abstract bibtex
OBJECTIVES: Some large population-based studies have reported a dose-related increased risk of cataracts and glaucoma associated with use of inhaled corticosteroids (ICS) in patients with asthma or chronic obstructive pulmonary disease (COPD). We evaluated the association between use of ICS-containing products, specifically fluticasone propionate/salmeterol fixed-dose combination (FSC), and incidence of cataracts and glaucoma among patients with COPD in a large electronic medical record database in the United Kingdom. METHODS: We identified a cohort of patients aged 45 years and over with COPD in the General Practice Research Database (GPRD) between 2003 and 2006. Cases of incident cataracts or glaucoma were defined based on diagnosis and procedure codes and matched to controls from the risk set to estimate odds ratios (OR) and 95% confidence intervals (CI). The association with FSC or ICS exposure was modeled using conditional logistic regression. Medication exposure was assessed with respect to recency, duration, and number of prescriptions prior to the index date. Average daily dose was defined as none, low (1-250 mcg), medium (251-500 mcg), high (501-1000 mcg), or very high (1001+ mcg) using fluticasone propionate (FP) equivalents. RESULTS: We identified 2941 incident cataract cases and 327 incident glaucoma cases in the COPD cohort (n = 53,191). FSC or ICS prescriptions were not associated with risk of incident cataracts or glaucoma for any exposure category, after adjusting for confounders. We observed a lack of a dose response in all analyses, where low dose was the reference group. The odds of cataracts associated with FSC dose were medium OR: 1.1 (95% CI: 0.9-1.4); high OR: 1.2 (95% CI: 0.9-1.5); and very high OR: 1.2 (95% CI: 0.9-1.7). The odds of glaucoma associated with FSC dose: medium OR: 1.0 (95% CI: 0.5-2.1); high OR: 1.0 (95% CI: 0.5-2.0); and very high OR: 1.0 (95% CI: 0.4-2.8). CONCLUSIONS: FSC or other ICS exposure was not associated with an increased odds of cataracts or glaucoma, nor was a dose-response relationship observed in this population-based nested case-control study of COPD patients in the United Kingdom.
@article{miller_long-term_2011,
title = {Long-term use of fluticasone propionate/salmeterol fixed-dose combination and incidence of cataracts and glaucoma among chronic obstructive pulmonary disease patients in the {UK} {General} {Practice} {Research} {Database}},
volume = {6},
issn = {1178-2005},
doi = {10.2147/COPD.S14247},
abstract = {OBJECTIVES: Some large population-based studies have reported a dose-related increased risk of cataracts and glaucoma associated with use of inhaled corticosteroids (ICS) in patients with asthma or chronic obstructive pulmonary disease (COPD). We evaluated the association between use of ICS-containing products, specifically fluticasone propionate/salmeterol fixed-dose combination (FSC), and incidence of cataracts and glaucoma among patients with COPD in a large electronic medical record database in the United Kingdom.
METHODS: We identified a cohort of patients aged 45 years and over with COPD in the General Practice Research Database (GPRD) between 2003 and 2006. Cases of incident cataracts or glaucoma were defined based on diagnosis and procedure codes and matched to controls from the risk set to estimate odds ratios (OR) and 95\% confidence intervals (CI). The association with FSC or ICS exposure was modeled using conditional logistic regression. Medication exposure was assessed with respect to recency, duration, and number of prescriptions prior to the index date. Average daily dose was defined as none, low (1-250 mcg), medium (251-500 mcg), high (501-1000 mcg), or very high (1001+ mcg) using fluticasone propionate (FP) equivalents.
RESULTS: We identified 2941 incident cataract cases and 327 incident glaucoma cases in the COPD cohort (n = 53,191). FSC or ICS prescriptions were not associated with risk of incident cataracts or glaucoma for any exposure category, after adjusting for confounders. We observed a lack of a dose response in all analyses, where low dose was the reference group. The odds of cataracts associated with FSC dose were medium OR: 1.1 (95\% CI: 0.9-1.4); high OR: 1.2 (95\% CI: 0.9-1.5); and very high OR: 1.2 (95\% CI: 0.9-1.7). The odds of glaucoma associated with FSC dose: medium OR: 1.0 (95\% CI: 0.5-2.1); high OR: 1.0 (95\% CI: 0.5-2.0); and very high OR: 1.0 (95\% CI: 0.4-2.8).
CONCLUSIONS: FSC or other ICS exposure was not associated with an increased odds of cataracts or glaucoma, nor was a dose-response relationship observed in this population-based nested case-control study of COPD patients in the United Kingdom.},
language = {eng},
journal = {International Journal of Chronic Obstructive Pulmonary Disease},
author = {Miller, David P. and Watkins, Stephanie E. and Sampson, Tim and Davis, Kourtney J.},
year = {2011},
pmid = {22003292},
pmcid = {PMC3186745},
keywords = {Adrenergic beta-2 Receptor Agonists, Aged, Aged, 80 and over, Albuterol, Androstadienes, Bronchodilator Agents, Case-Control Studies, Cataract, Databases, Factual, Drug Administration Schedule, Drug Combinations, Female, General Practice, Glaucoma, Great Britain, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Pulmonary Disease, Chronic Obstructive, Risk, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, cataracts, fluticasone propionate/salmeterol, incidence, inhaled corticosteroids},
pages = {467--476}
}2010 (4)
iqr: A Tool for the Construction of Multi-level Simulations of Brain and Behaviour. Bernardet, U. & Verschure, P., F. Neuroinformatics, 8(2):113-34, Humana Press Inc., 2010.
![iqr: A Tool for the Construction of Multi-level Simulations of Brain and Behaviour. [pdf]](https://bibbase.org/img/filetypes/pdf.svg "pdf")
Paper Website abstract bibtex
Paper Website abstract bibtex The brain is the most complex system we know of. Despite the wealth of data available in neuroscience, our understanding of this system is still very limited. Here we argue that an essential component in our arsenal of methods to advance our understanding of the brain is the construction of artificial brain-like systems. In this way we can encompass the multi-level organisation of the brain and its role in the context of the complete embodied real-world and real-time perceiving and behaving system. Hence, on the one hand, we must be able to develop and validate theories of brains as closing the loop between perception and action, and on the other hand as interacting with the real world. Evidence is growing that one of the sources of the computational power of neuronal systems lies in the massive and specific connectivity, rather than the complexity of single elements. To meet these challenges-multiple levels of organisation, sophisticated connectivity, and the interaction of neuronal models with the real-world-we have developed a multi-level neuronal simulation environment, iqr. This framework deals with these requirements by directly transforming them into the core elements of the simulation environment itself. iqr provides a means to design complex neuronal models graphically, and to visualise and analyse their properties on-line. In iqr connectivity is defined in a flexible, yet compact way, and simulations run at a high speed, which allows the control of real-world devices-robots in the broader sense-in real-time. The architecture of iqr is modular, providing the possibility to write new neuron, and synapse types, and custom interfaces to other hardware systems. The code of iqr is publicly accessible under the GNU General Public License (GPL). iqr has been in use since 1996 and has been the core tool for a large number of studies ranging from detailed models of neuronal systems like the cerebral cortex, and the cerebellum, to robot based models of perception, cognition and action to large-scale real-world systems. In addition, iqr has been widely used over many years to introduce students to neuronal simulation and neuromorphic control. In this paper we outline the conceptual and methodological background of iqr and its design philosophy. Thereafter we present iqr's main features and computational properties. Finally, we describe a number of projects using iqr, singling out how iqr is used for building a "synthetic insect".
@article{
title = {iqr: A Tool for the Construction of Multi-level Simulations of Brain and Behaviour.},
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year = {2010},
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pages = {113-34},
volume = {8},
websites = {http://www.ncbi.nlm.nih.gov/pubmed/20502987},
publisher = {Humana Press Inc.},
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abstract = {The brain is the most complex system we know of. Despite the wealth of data available in neuroscience, our understanding of this system is still very limited. Here we argue that an essential component in our arsenal of methods to advance our understanding of the brain is the construction of artificial brain-like systems. In this way we can encompass the multi-level organisation of the brain and its role in the context of the complete embodied real-world and real-time perceiving and behaving system. Hence, on the one hand, we must be able to develop and validate theories of brains as closing the loop between perception and action, and on the other hand as interacting with the real world. Evidence is growing that one of the sources of the computational power of neuronal systems lies in the massive and specific connectivity, rather than the complexity of single elements. To meet these challenges-multiple levels of organisation, sophisticated connectivity, and the interaction of neuronal models with the real-world-we have developed a multi-level neuronal simulation environment, iqr. This framework deals with these requirements by directly transforming them into the core elements of the simulation environment itself. iqr provides a means to design complex neuronal models graphically, and to visualise and analyse their properties on-line. In iqr connectivity is defined in a flexible, yet compact way, and simulations run at a high speed, which allows the control of real-world devices-robots in the broader sense-in real-time. The architecture of iqr is modular, providing the possibility to write new neuron, and synapse types, and custom interfaces to other hardware systems. The code of iqr is publicly accessible under the GNU General Public License (GPL). iqr has been in use since 1996 and has been the core tool for a large number of studies ranging from detailed models of neuronal systems like the cerebral cortex, and the cerebellum, to robot based models of perception, cognition and action to large-scale real-world systems. In addition, iqr has been widely used over many years to introduce students to neuronal simulation and neuromorphic control. In this paper we outline the conceptual and methodological background of iqr and its design philosophy. Thereafter we present iqr's main features and computational properties. Finally, we describe a number of projects using iqr, singling out how iqr is used for building a "synthetic insect".},
bibtype = {article},
author = {Bernardet, Ulysses and Verschure, Paul F.M.J.},
journal = {Neuroinformatics},
number = {2}
}Natural language processing for the development of a clinical registry: a validation study in intraductal papillary mucinous neoplasms. Al-Haddad, M. A., Friedlin, J., Kesterson, J., Waters, J. A., Aguilar-Saavedra, J. R., & Schmidt, C. M. HPB: the official journal of the International Hepato Pancreato Biliary Association, 12(10):688–695, December, 2010.
doi abstract bibtex
doi abstract bibtex
BACKGROUND: Medical natural language processing (NLP) systems have been developed to identify, extract and encode information within clinical narrative text. However, the role of NLP in clinical research and patient care remains limited. Pancreatic cysts are common. Some pancreatic cysts, such as intraductal papillary mucinous neoplasms (IPMNs), have malignant potential and require extended periods of surveillance. We seek to develop a novel NLP system that could be applied in our clinical network to develop a functional registry of IPMN patients. OBJECTIVES: This study aims to validate the accuracy of our novel NLP system in the identification of surgical patients with pathologically confirmed IPMN in comparison with our pre-existing manually created surgical database (standard reference). METHODS: The Regenstrief EXtraction Tool (REX) was used to extract pancreatic cyst patient data from medical text files from Indiana University Health. The system was assessed periodically by direct sampling and review of medical records. Results were compared with the standard reference. RESULTS: Natural language processing detected 5694 unique patients with pancreas cysts, in 215 of whom surgical pathology had confirmed IPMN. The NLP software identified all but seven patients present in the surgical database and identified an additional 37 IPMN patients not previously included in the surgical database. Using the standard reference, the sensitivity of the NLP program was 97.5% (95% confidence interval [CI] 94.8-98.9%) and its positive predictive value was 95.5% (95% CI 92.3-97.5%). CONCLUSIONS: Natural language processing is a reliable and accurate method for identifying selected patient cohorts and may facilitate the identification and follow-up of patients with IPMN.
@article{al-haddad_natural_2010,
title = {Natural language processing for the development of a clinical registry: a validation study in intraductal papillary mucinous neoplasms},
volume = {12},
issn = {1477-2574},
shorttitle = {Natural language processing for the development of a clinical registry},
doi = {10.1111/j.1477-2574.2010.00235.x},
abstract = {BACKGROUND: Medical natural language processing (NLP) systems have been developed to identify, extract and encode information within clinical narrative text. However, the role of NLP in clinical research and patient care remains limited. Pancreatic cysts are common. Some pancreatic cysts, such as intraductal papillary mucinous neoplasms (IPMNs), have malignant potential and require extended periods of surveillance. We seek to develop a novel NLP system that could be applied in our clinical network to develop a functional registry of IPMN patients.
OBJECTIVES: This study aims to validate the accuracy of our novel NLP system in the identification of surgical patients with pathologically confirmed IPMN in comparison with our pre-existing manually created surgical database (standard reference).
METHODS: The Regenstrief EXtraction Tool (REX) was used to extract pancreatic cyst patient data from medical text files from Indiana University Health. The system was assessed periodically by direct sampling and review of medical records. Results were compared with the standard reference.
RESULTS: Natural language processing detected 5694 unique patients with pancreas cysts, in 215 of whom surgical pathology had confirmed IPMN. The NLP software identified all but seven patients present in the surgical database and identified an additional 37 IPMN patients not previously included in the surgical database. Using the standard reference, the sensitivity of the NLP program was 97.5\% (95\% confidence interval [CI] 94.8-98.9\%) and its positive predictive value was 95.5\% (95\% CI 92.3-97.5\%).
CONCLUSIONS: Natural language processing is a reliable and accurate method for identifying selected patient cohorts and may facilitate the identification and follow-up of patients with IPMN.},
language = {eng},
number = {10},
journal = {HPB: the official journal of the International Hepato Pancreato Biliary Association},
author = {Al-Haddad, Mohammad A. and Friedlin, Jeff and Kesterson, Joe and Waters, Joshua A. and Aguilar-Saavedra, Juan R. and Schmidt, C. Max},
month = dec,
year = {2010},
pmid = {21083794},
pmcid = {PMC3003479},
keywords = {Humans, Reproducibility of Results, Natural Language Processing, Prognosis, Registries, Software, Pancreatic Neoplasms, Data Mining, Time Factors, Indiana, Carcinoma, Pancreatic Ductal, Carcinoma, Papillary, Disease Progression, Neoplasms, Cystic, Mucinous, and Serous, Pancreatic Cyst, Precancerous Conditions},
pages = {688--695},
file = {Full Text:/Users/yifu/Zotero/storage/AYMV9BUZ/Al-Haddad et al. - 2010 - Natural language processing for the development of.pdf:application/pdf},
}Behavior and serotonergic disorders in rats exposed prenatally to valproate: a model for autism. Dufour-Rainfray, D., Vourc'h, P., Guisquet, A. L., Garreau, L., Ternant, D., Bodard, S., Jaumain, E., Gulhan, Z., Belzung, C., Andres, C. R., Chalon, S., & Guilloteau, D. Neuroscience Letters, 470(1):55--59, February, 2010.
doi abstract bibtex
doi abstract bibtex
In order to explore whether some aspects of the autistic phenotype could be related to impairment of the serotonergic system, we chose an animal model which mimics a potential cause of autism, i.e. rats exposed to valproate (VPA) on the 9th embryonic day (E9). Previous studies have suggested that VPA exposure in rats at E9 caused a dramatic shift in the distribution of serotonergic neurons on postnatal day 50 (PND50). Behavioral studies have also been performed but on rats that were exposed to VPA later (E12.5). Our aim was to test whether VPA exposure at E9 induces comparable behavioral impairments than at E12.5 and causes serotonergic impairments which could be related to behavioral modifications. The results showed significant behavioral impairments such as a lower tendency to initiate social interactions and hyperlocomotor activity in juvenile male rats. The serotonin levels of these animals at PND50 were decreased (-46%) in the hippocampus, a structure involved in social behavior. This study suggests that VPA could have a direct or indirect action on the serotonergic system as early as the progenitor cell stage. Early embryonic exposure to VPA in rats provides a good model for several specific aspects of autism and should help to continue to explore pathophysiological hypotheses.
@article{ dufour-rainfray_behavior_2010,
title = {Behavior and serotonergic disorders in rats exposed prenatally to valproate: a model for autism},
volume = {470},
issn = {1872-7972},
shorttitle = {Behavior and serotonergic disorders in rats exposed prenatally to valproate},
doi = {10.1016/j.neulet.2009.12.054},
abstract = {In order to explore whether some aspects of the autistic phenotype could be related to impairment of the serotonergic system, we chose an animal model which mimics a potential cause of autism, i.e. rats exposed to valproate ({VPA}) on the 9th embryonic day (E9). Previous studies have suggested that {VPA} exposure in rats at E9 caused a dramatic shift in the distribution of serotonergic neurons on postnatal day 50 ({PND}50). Behavioral studies have also been performed but on rats that were exposed to {VPA} later (E12.5). Our aim was to test whether {VPA} exposure at E9 induces comparable behavioral impairments than at E12.5 and causes serotonergic impairments which could be related to behavioral modifications. The results showed significant behavioral impairments such as a lower tendency to initiate social interactions and hyperlocomotor activity in juvenile male rats. The serotonin levels of these animals at {PND}50 were decreased (-46%) in the hippocampus, a structure involved in social behavior. This study suggests that {VPA} could have a direct or indirect action on the serotonergic system as early as the progenitor cell stage. Early embryonic exposure to {VPA} in rats provides a good model for several specific aspects of autism and should help to continue to explore pathophysiological hypotheses.},
language = {eng},
number = {1},
journal = {Neuroscience Letters},
author = {Dufour-Rainfray, Diane and Vourc'h, Patrick and Le Guisquet, Anne-Marie and Garreau, Lucette and Ternant, David and Bodard, Sylvie and Jaumain, Emilie and Gulhan, Zuhal and Belzung, Catherine and Andres, Christian R. and Chalon, Sylvie and Guilloteau, Denis},
month = {February},
year = {2010},
pmid = {20036713},
keywords = {Animals, Autistic Disorder, Behavior, Animal, Brain, Disease Models, Animal, Female, {GABA} Agents, Hippocampus, Hydroxyindoleacetic Acid, Male, Motor Activity, Pregnancy, Prenatal Exposure Delayed Effects, {RNA}-Binding Proteins, Rats, Rats, Wistar, Serotonin, Social Behavior, Time Factors, Valproic Acid},
pages = {55--59}
}Risk of death during and after opiate substitution treatment in primary care: prospective observational study in UK General Practice Research Database. Cornish, R., Macleod, J., Strang, J., Vickerman, P., & Hickman, M. BMJ (Clinical research ed.), 341:c5475, 2010.
abstract bibtex
abstract bibtex
OBJECTIVE: To investigate the effect of opiate substitution treatment at the beginning and end of treatment and according to duration of treatment. DESIGN: Prospective cohort study. Setting UK General Practice Research Database. PARTICIPANTS: Primary care patients with a diagnosis of substance misuse prescribed methadone or buprenorphine during 1990-2005. 5577 patients with 267 003 prescriptions for opiate substitution treatment followed-up (17 732 years) until one year after the expiry of their last prescription, the date of death before this time had elapsed, or the date of transfer away from the practice. MAIN OUTCOME MEASURES: Mortality rates and rate ratios comparing periods in and out of treatment adjusted for sex, age, calendar year, and comorbidity; standardised mortality ratios comparing opiate users' mortality with general population mortality rates. RESULTS: Crude mortality rates were 0.7 per 100 person years on opiate substitution treatment and 1.3 per 100 person years off treatment; standardised mortality ratios were 5.3 (95% confidence interval 4.0 to 6.8) on treatment and 10.9 (9.0 to 13.1) off treatment. Men using opiates had approximately twice the risk of death of women (morality rate ratio 2.0, 1.4 to 2.9). In the first two weeks of opiate substitution treatment the crude mortality rate was 1.7 per 100 person years: 3.1 (1.5 to 6.6) times higher (after adjustment for sex, age group, calendar period, and comorbidity) than the rate during the rest of time on treatment. The crude mortality rate was 4.8 per 100 person years in weeks 1-2 after treatment stopped, 4.3 in weeks 3-4, and 0.95 during the rest of time off treatment: 9 (5.4 to 14.9), 8 (4.7 to 13.7), and 1.9 (1.3 to 2.8) times higher than the baseline risk of mortality during treatment. Opiate substitution treatment has a greater than 85% chance of reducing overall mortality among opiate users if the average duration approaches or exceeds 12 months. CONCLUSIONS: Clinicians and patients should be aware of the increased mortality risk at the start of opiate substitution treatment and immediately after stopping treatment. Further research is needed to investigate the effect of average duration of opiate substitution treatment on drug related mortality.
@article{cornish_risk_2010,
title = {Risk of death during and after opiate substitution treatment in primary care: prospective observational study in {UK} {General} {Practice} {Research} {Database}},
volume = {341},
issn = {1756-1833},
shorttitle = {Risk of death during and after opiate substitution treatment in primary care},
abstract = {OBJECTIVE: To investigate the effect of opiate substitution treatment at the beginning and end of treatment and according to duration of treatment.
DESIGN: Prospective cohort study. Setting UK General Practice Research Database.
PARTICIPANTS: Primary care patients with a diagnosis of substance misuse prescribed methadone or buprenorphine during 1990-2005. 5577 patients with 267 003 prescriptions for opiate substitution treatment followed-up (17 732 years) until one year after the expiry of their last prescription, the date of death before this time had elapsed, or the date of transfer away from the practice.
MAIN OUTCOME MEASURES: Mortality rates and rate ratios comparing periods in and out of treatment adjusted for sex, age, calendar year, and comorbidity; standardised mortality ratios comparing opiate users' mortality with general population mortality rates.
RESULTS: Crude mortality rates were 0.7 per 100 person years on opiate substitution treatment and 1.3 per 100 person years off treatment; standardised mortality ratios were 5.3 (95\% confidence interval 4.0 to 6.8) on treatment and 10.9 (9.0 to 13.1) off treatment. Men using opiates had approximately twice the risk of death of women (morality rate ratio 2.0, 1.4 to 2.9). In the first two weeks of opiate substitution treatment the crude mortality rate was 1.7 per 100 person years: 3.1 (1.5 to 6.6) times higher (after adjustment for sex, age group, calendar period, and comorbidity) than the rate during the rest of time on treatment. The crude mortality rate was 4.8 per 100 person years in weeks 1-2 after treatment stopped, 4.3 in weeks 3-4, and 0.95 during the rest of time off treatment: 9 (5.4 to 14.9), 8 (4.7 to 13.7), and 1.9 (1.3 to 2.8) times higher than the baseline risk of mortality during treatment. Opiate substitution treatment has a greater than 85\% chance of reducing overall mortality among opiate users if the average duration approaches or exceeds 12 months.
CONCLUSIONS: Clinicians and patients should be aware of the increased mortality risk at the start of opiate substitution treatment and immediately after stopping treatment. Further research is needed to investigate the effect of average duration of opiate substitution treatment on drug related mortality.},
language = {eng},
journal = {BMJ (Clinical research ed.)},
author = {Cornish, Rosie and Macleod, John and Strang, John and Vickerman, Peter and Hickman, Matt},
year = {2010},
pmid = {20978062},
pmcid = {PMC2965139},
keywords = {Adolescent, Adult, Buprenorphine, Female, Great Britain, Humans, Male, Methadone, Middle Aged, Narcotics, Opioid-Related Disorders, Prospective Studies, Risk Factors, Time Factors, Young Adult},
pages = {c5475}
}2009 (10)
mhFLIM: Resolution of heterogeneous fluorescence decays in widefield lifetime microscopy. Schlachter, S., Elder, Esposito, Kaminski, Frank, Geest, V., Elder, a., D., Esposito, A., Kaminski, G., S., Frank, J., H., van Geest, L., K., & Kaminski, C., F. Optics Express, 17(3):1557-1570, 1, 2009.
Paper Website abstract bibtex
Paper Website abstract bibtex Frequency-domain fluorescence lifetime imaging microscopy (FD-FLIM) is a fast and accurate way of measuring fluorescence lifetimes in widefield microscopy. However, the resolution of multiple exponential fluorescence decays has remained beyond the reach of most practical FD-FLIM systems. In this paper we describe the implementation of FD-FLIM using a 40MHz pulse train derived from a supercontinuum source for excitation. The technique, which we term multi-harmonic FLIM (mhFLIM), makes it possible to accurately resolve biexponential decays of fluorophores without any a priori information. The system's performance is demonstrated using a mixture of spectrally similar dyes of known composition and also on a multiply-labeled biological sample. The results are compared to those obtained from time correlated single photon counting (TCSPC) microscopy and a good level of agreement is achieved. We also demonstrate the first practical application of an algorithm derived by G. Weber [1] for analysing mhFLIM data. Because it does not require nonlinear minimisation, it offers potential for realtime analysis during acquisition. (C) 2009 Optical Society of America
@article{
title = {mhFLIM: Resolution of heterogeneous fluorescence decays in widefield lifetime microscopy},
type = {article},
year = {2009},
identifiers = {[object Object]},
keywords = {Algorithms,Calibration,Cell Line,Coloring Agents,Coloring Agents: chemistry,Energy-Transfer,Flim,Fluorescence,Fourier Analysis,Frequency-Domain,Humans,Imaging Microscopy,Living Cells,Microscopy,Microscopy: instrumentation,Microscopy: methods,Phase,Solutions,System,Time Factors,Tumor},
pages = {1557-1570},
volume = {17},
websites = {http://www.ncbi.nlm.nih.gov/pubmed/19188985,http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=000263432400044,file://localhost/Users/cfk23/Documents/Papers/2009/Schlachter/Opt Express 2009 Schlachter.pdf,papers://5b342310-4c1b-4925-bbf8-38f14091331d/Paper/p51},
month = {1},
day = {2},
city = {Univ Cambridge, Dept Chem Engn & Biotechnol, Cambridge CB2 1RA, England},
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abstract = {Frequency-domain fluorescence lifetime imaging microscopy (FD-FLIM) is a fast and accurate way of measuring fluorescence lifetimes in widefield microscopy. However, the resolution of multiple exponential fluorescence decays has remained beyond the reach of most practical FD-FLIM systems. In this paper we describe the implementation of FD-FLIM using a 40MHz pulse train derived from a supercontinuum source for excitation. The technique, which we term multi-harmonic FLIM (mhFLIM), makes it possible to accurately resolve biexponential decays of fluorophores without any a priori information. The system's performance is demonstrated using a mixture of spectrally similar dyes of known composition and also on a multiply-labeled biological sample. The results are compared to those obtained from time correlated single photon counting (TCSPC) microscopy and a good level of agreement is achieved. We also demonstrate the first practical application of an algorithm derived by G. Weber [1] for analysing mhFLIM data. Because it does not require nonlinear minimisation, it offers potential for realtime analysis during acquisition. (C) 2009 Optical Society of America},
bibtype = {article},
author = {Schlachter, S and Elder, undefined and Esposito, undefined and Kaminski, undefined and Frank, undefined and Geest, Van and Elder, a D and Esposito, A and Kaminski, G S and Frank, J H and van Geest, L K and Kaminski, C F},
journal = {Optics Express},
number = {3}
}A new learning paradigm: learning using privileged information. Vapnik, V. & Vashist, A. Neural Networks, 22(5-6):544--57, Elsevier Ltd, 2009.
doi bibtex
doi bibtex
@Article{Vapnik_2009_15070,
author = {Vapnik, V. and Vashist, A.},
journal = {Neural Networks},
number = {5-6},
pages = {544--57},
publisher = {Elsevier Ltd},
title = {A new learning paradigm: learning using privileged information.},
volume = {22},
year = {2009},
issn = {1879-2782},
keywords = {Algorithms,Artificial Intelligence,Bayes Theorem,Databases, Genetic,Forecasting,Forecasting: methods,Information Dissemination,Language,Learning,Mathematical Concepts,Protein Conformation,Proteins,Proteins: classification,Sequence Analysis, Protein,Sequence Analysis, Protein: methods,Time Factors},
doi = {10.1016/j.neunet.2009.06.042},
pmid = {19632812},
title_with_no_special_chars = {A new learning paradigm learning using privileged information}
}A new tool for assessing human movement: the Kinematic Assessment Tool. Culmer, P., R., Levesley, M., C., Mon-Williams, M., & Williams, J., H., G. Journal of neuroscience methods, 184(1):184-92, 10, 2009.
Paper Website abstract bibtex
Paper Website abstract bibtex The study of human behaviour ultimately requires the documentation of human movement. In some instances movements can be recorded through a simple button press on a computer input device. In other situations responses can be captured through questionnaire surveys. Nevertheless, there is a need within many neuroscience settings to capture how complex movements unfold over time (human kinematics). Current methods of measuring human kinematics range from accurate but multifarious laboratory configurations to portable but simplistic and time-consuming paper and pen methods. We describe a new system for recording the end-point of human movement that has the power of laboratory measures but the advantages of pen-and-paper tests: the Kinematic Assessment Tool. KAT provides a highly portable system capable of measuring human movement in configurable visual-spatial tasks. The usefulness of the system is shown in a study where 12 participants undertook a tracing and copying task using their preferred and non-preferred hand. The results show that it is possible to capture behaviour within complex tasks and quantify performance using objective measures automatically generated by the KAT system. The utility of these measures was indexed by our ability to distinguish the performance of the preferred and non-preferred hand using a single variable.
@article{
title = {A new tool for assessing human movement: the Kinematic Assessment Tool.},
type = {article},
year = {2009},
identifiers = {[object Object]},
keywords = {Adult,Biomechanical Phenomena,Computers,Hand,Humans,Motor Activity,Movement,Signal Processing, Computer-Assisted,Software,Task Performance and Analysis,Time Factors,Young Adult},
pages = {184-92},
volume = {184},
websites = {http://www.sciencedirect.com/science/article/pii/S016502700900404X},
month = {10},
day = {30},
id = {600e7210-e036-3377-96e3-b28cb73804c7},
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abstract = {The study of human behaviour ultimately requires the documentation of human movement. In some instances movements can be recorded through a simple button press on a computer input device. In other situations responses can be captured through questionnaire surveys. Nevertheless, there is a need within many neuroscience settings to capture how complex movements unfold over time (human kinematics). Current methods of measuring human kinematics range from accurate but multifarious laboratory configurations to portable but simplistic and time-consuming paper and pen methods. We describe a new system for recording the end-point of human movement that has the power of laboratory measures but the advantages of pen-and-paper tests: the Kinematic Assessment Tool. KAT provides a highly portable system capable of measuring human movement in configurable visual-spatial tasks. The usefulness of the system is shown in a study where 12 participants undertook a tracing and copying task using their preferred and non-preferred hand. The results show that it is possible to capture behaviour within complex tasks and quantify performance using objective measures automatically generated by the KAT system. The utility of these measures was indexed by our ability to distinguish the performance of the preferred and non-preferred hand using a single variable.},
bibtype = {article},
author = {Culmer, Peter R and Levesley, Martin C and Mon-Williams, Mark and Williams, Justin H G},
journal = {Journal of neuroscience methods},
number = {1}
}New particle formation in forests inhibited by isoprene emissions. Kiendler-Scharr, A., Wildt, J., Dal Maso, M., Hohaus, T., Kleist, E., Mentel, T., F., Tillmann, R., Uerlings, R., Schurr, U., & Wahner, A. Nature, 461(7262):381-4, 9, 2009.
Paper Website abstract bibtex
Paper Website abstract bibtex It has been suggested that volatile organic compounds (VOCs) are involved in organic aerosol formation, which in turn affects radiative forcing and climate. The most abundant VOCs emitted by terrestrial vegetation are isoprene and its derivatives, such as monoterpenes and sesquiterpenes. New particle formation in boreal regions is related to monoterpene emissions and causes an estimated negative radiative forcing of about -0.2 to -0.9 W m(-2). The annual variation in aerosol growth rates during particle nucleation events correlates with the seasonality of monoterpene emissions of the local vegetation, with a maximum during summer. The frequency of nucleation events peaks, however, in spring and autumn. Here we present evidence from simulation experiments conducted in a plant chamber that isoprene can significantly inhibit new particle formation. The process leading to the observed decrease in particle number concentration is linked to the high reactivity of isoprene with the hydroxyl radical (OH). The suppression is stronger with higher concentrations of isoprene, but with little dependence on the specific VOC mixture emitted by trees. A parameterization of the observed suppression factor as a function of isoprene concentration suggests that the number of new particles produced depends on the OH concentration and VOCs involved in the production of new particles undergo three to four steps of oxidation by OH. Our measurements simulate conditions that are typical for forested regions and may explain the observed seasonality in the frequency of aerosol nucleation events, with a lower number of nucleation events during summer compared to autumn and spring. Biogenic emissions of isoprene are controlled by temperature and light, and if the relative isoprene abundance of biogenic VOC emissions increases in response to climate change or land use change, the new particle formation potential may decrease, thus damping the aerosol negative radiative forcing effect.
@article{
title = {New particle formation in forests inhibited by isoprene emissions.},
type = {article},
year = {2009},
identifiers = {[object Object]},
keywords = {Aerosols,Aerosols: analysis,Aerosols: metabolism,Air,Air: analysis,Betula,Betula: drug effects,Betula: metabolism,Butadienes,Butadienes: analysis,Butadienes: pharmacology,Carbon,Carbon: analysis,Environment, Controlled,Fagus,Fagus: drug effects,Fagus: metabolism,Hemiterpenes,Hemiterpenes: analysis,Hemiterpenes: pharmacology,Hemiterpenes: secretion,Hydroxyl Radical,Hydroxyl Radical: analysis,Hydroxyl Radical: metabolism,Light,Monoterpenes,Monoterpenes: metabolism,Monoterpenes: pharmacology,Oxidation-Reduction,Pentanes,Pentanes: analysis,Pentanes: pharmacology,Picea,Picea: drug effects,Picea: metabolism,Seasons,Temperature,Time Factors,Trees,Trees: drug effects,Trees: metabolism,Volatile Organic Compounds,Volatile Organic Compounds: analysis,Volatile Organic Compounds: metabolism},
pages = {381-4},
volume = {461},
websites = {http://www.ncbi.nlm.nih.gov/pubmed/19759617},
month = {9},
day = {17},
id = {80526aa9-4829-365e-8163-9ff855fb80d5},
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abstract = {It has been suggested that volatile organic compounds (VOCs) are involved in organic aerosol formation, which in turn affects radiative forcing and climate. The most abundant VOCs emitted by terrestrial vegetation are isoprene and its derivatives, such as monoterpenes and sesquiterpenes. New particle formation in boreal regions is related to monoterpene emissions and causes an estimated negative radiative forcing of about -0.2 to -0.9 W m(-2). The annual variation in aerosol growth rates during particle nucleation events correlates with the seasonality of monoterpene emissions of the local vegetation, with a maximum during summer. The frequency of nucleation events peaks, however, in spring and autumn. Here we present evidence from simulation experiments conducted in a plant chamber that isoprene can significantly inhibit new particle formation. The process leading to the observed decrease in particle number concentration is linked to the high reactivity of isoprene with the hydroxyl radical (OH). The suppression is stronger with higher concentrations of isoprene, but with little dependence on the specific VOC mixture emitted by trees. A parameterization of the observed suppression factor as a function of isoprene concentration suggests that the number of new particles produced depends on the OH concentration and VOCs involved in the production of new particles undergo three to four steps of oxidation by OH. Our measurements simulate conditions that are typical for forested regions and may explain the observed seasonality in the frequency of aerosol nucleation events, with a lower number of nucleation events during summer compared to autumn and spring. Biogenic emissions of isoprene are controlled by temperature and light, and if the relative isoprene abundance of biogenic VOC emissions increases in response to climate change or land use change, the new particle formation potential may decrease, thus damping the aerosol negative radiative forcing effect.},
bibtype = {article},
author = {Kiendler-Scharr, Astrid and Wildt, Jürgen and Dal Maso, Miikka and Hohaus, Thorsten and Kleist, Einhard and Mentel, Thomas F and Tillmann, Ralf and Uerlings, Ricarda and Schurr, Uli and Wahner, Andreas},
journal = {Nature},
number = {7262}
}Spike inference from calcium imaging using sequential Monte Carlo methods. Vogelstein, J., T., Watson, B., O., Packer, A., M., Yuste, R., Jedynak, B., M., & Paninski, L. Biophysical Journal, 97(2):636-655, 7, 2009.
abstract bibtex
abstract bibtex
As recent advances in calcium sensing technologies facilitate simultaneously imaging action potentials in neuronal populations, complementary analytical tools must also be developed to maximize the utility of this experimental paradigm. Although the observations here are fluorescence movies, the signals of interest--spike trains and/or time varying intracellular calcium concentrations--are hidden. Inferring these hidden signals is often problematic due to noise, nonlinearities, slow imaging rate, and unknown biophysical parameters. We overcome these difficulties by developing sequential Monte Carlo methods (particle filters) based on biophysical models of spiking, calcium dynamics, and fluorescence. We show that even in simple cases, the particle filters outperform the optimal linear (i.e., Wiener) filter, both by obtaining better estimates and by providing error bars. We then relax a number of our model assumptions to incorporate nonlinear saturation of the fluorescence signal, as well external stimulus and spike history dependence (e.g., refractoriness) of the spike trains. Using both simulations and in vitro fluorescence observations, we demonstrate temporal superresolution by inferring when within a frame each spike occurs. Furthermore, the model parameters may be estimated using expectation maximization with only a very limited amount of data (e.g., approximately 5-10 s or 5-40 spikes), without the requirement of any simultaneous electrophysiology or imaging experiments.
@article{
title = {Spike inference from calcium imaging using sequential Monte Carlo methods.},
type = {article},
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pages = {636-655},
volume = {97},
websites = {http://dx.doi.org/10.1016/j.bpj.2008.08.005},
month = {7},
institution = {Department of Neuroscience, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA. joshuav@jhu.edu},
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abstract = {As recent advances in calcium sensing technologies facilitate simultaneously imaging action potentials in neuronal populations, complementary analytical tools must also be developed to maximize the utility of this experimental paradigm. Although the observations here are fluorescence movies, the signals of interest--spike trains and/or time varying intracellular calcium concentrations--are hidden. Inferring these hidden signals is often problematic due to noise, nonlinearities, slow imaging rate, and unknown biophysical parameters. We overcome these difficulties by developing sequential Monte Carlo methods (particle filters) based on biophysical models of spiking, calcium dynamics, and fluorescence. We show that even in simple cases, the particle filters outperform the optimal linear (i.e., Wiener) filter, both by obtaining better estimates and by providing error bars. We then relax a number of our model assumptions to incorporate nonlinear saturation of the fluorescence signal, as well external stimulus and spike history dependence (e.g., refractoriness) of the spike trains. Using both simulations and in vitro fluorescence observations, we demonstrate temporal superresolution by inferring when within a frame each spike occurs. Furthermore, the model parameters may be estimated using expectation maximization with only a very limited amount of data (e.g., approximately 5-10 s or 5-40 spikes), without the requirement of any simultaneous electrophysiology or imaging experiments.},
bibtype = {article},
author = {Vogelstein, Joshua T. and Watson, Brendon O and Packer, Adam M and Yuste, Rafael and Jedynak, Bruno M and Paninski, Liam},
journal = {Biophysical Journal},
number = {2}
}Short-term menatetrenone therapy increases gamma-carboxylation of osteocalcin with a moderate increase of bone turnover in postmenopausal osteoporosis: a randomized prospective study. Shiraki, M. & Itabashi, A. Journal of Bone and Mineral Metabolism, 27(3):333–340, 2009.
doi abstract bibtex
doi abstract bibtex
The effect of vitamin K(2) (menatetrenone) on bone turnover was investigated in postmenopausal patients with osteoporosis. A 6-month open-label, randomized prospective study was conducted in 109 patients. The control group (n = 53) received calcium aspartate (133.8 mg of elemental calcium daily), while the menatetrenone group (n = 56) received 45 mg of menatetrenone daily for 6 months. Serum and urinary levels of bone turnover markers were monitored. The serum level of undercarboxylated osteocalcin (uc-OC) was significantly lower (P \textless 0.001) in the menatetrenone group than in the control group (at 1 month), while there was a higher level of osteocalcin containing gamma-carboxylated glutamic acid (Gla-OC) in the menatetrenone group than the control group (P = 0.018). Significant differences of uc-OC and Gla-OC between the two groups were observed from 1 month onward. In addition, a higher level of intact osteocalcin was found in the menatetrenone group compared with the control group after 6 months (P = 0.006). Assessment of bone resorption markers showed that menatetrenone therapy was associated with significantly higher urinary N-telopeptide of type I collagen (NTX) excretion compared with the control group after 6 months, while there was no significant difference of urinary deoxypyridinoline excretion between the two groups. In conclusion, one month of menatetrenone therapy enhanced the secretion and gamma-carboxylation of osteocalcin, while urinary NTX excretion was increased after 6 months of treatment. Further investigations are required to determine whether the effects of menatetrenone on bone turnover are associated with fracture prevention.
@article{shiraki_short-term_2009,
title = {Short-term menatetrenone therapy increases gamma-carboxylation of osteocalcin with a moderate increase of bone turnover in postmenopausal osteoporosis: a randomized prospective study},
volume = {27},
issn = {0914-8779},
shorttitle = {Short-term menatetrenone therapy increases gamma-carboxylation of osteocalcin with a moderate increase of bone turnover in postmenopausal osteoporosis},
doi = {10.1007/s00774-008-0034-6},
abstract = {The effect of vitamin K(2) (menatetrenone) on bone turnover was investigated in postmenopausal patients with osteoporosis. A 6-month open-label, randomized prospective study was conducted in 109 patients. The control group (n = 53) received calcium aspartate (133.8 mg of elemental calcium daily), while the menatetrenone group (n = 56) received 45 mg of menatetrenone daily for 6 months. Serum and urinary levels of bone turnover markers were monitored. The serum level of undercarboxylated osteocalcin (uc-OC) was significantly lower (P {\textless} 0.001) in the menatetrenone group than in the control group (at 1 month), while there was a higher level of osteocalcin containing gamma-carboxylated glutamic acid (Gla-OC) in the menatetrenone group than the control group (P = 0.018). Significant differences of uc-OC and Gla-OC between the two groups were observed from 1 month onward. In addition, a higher level of intact osteocalcin was found in the menatetrenone group compared with the control group after 6 months (P = 0.006). Assessment of bone resorption markers showed that menatetrenone therapy was associated with significantly higher urinary N-telopeptide of type I collagen (NTX) excretion compared with the control group after 6 months, while there was no significant difference of urinary deoxypyridinoline excretion between the two groups. In conclusion, one month of menatetrenone therapy enhanced the secretion and gamma-carboxylation of osteocalcin, while urinary NTX excretion was increased after 6 months of treatment. Further investigations are required to determine whether the effects of menatetrenone on bone turnover are associated with fracture prevention.},
language = {eng},
number = {3},
journal = {Journal of Bone and Mineral Metabolism},
author = {Shiraki, Masataka and Itabashi, Akira},
year = {2009},
pmid = {19172219},
keywords = {Aged, Biomarkers, Bone Density, Bone Remodeling, Calcium, Female, Hemostatics, Hormones, Humans, Lumbar Vertebrae, Osteocalcin, Osteoporosis, Postmenopausal, Protein Processing, Post-Translational, Time Factors, Treatment Outcome, Vitamin K 2},
pages = {333--340},
}A face feature space in the macaque temporal lobe. Freiwald, W. A, Tsao, D. Y, & Livingstone, M. S Nat Neurosci, 12(9):1187–1196, 2009. Place: United States ISBN: 1546-1726
doi abstract bibtex
doi abstract bibtex
The ability of primates to effortlessly recognize faces has been attributed to the existence of specialized face areas. One such area, the macaque middle face patch, consists almost entirely of cells that are selective for faces, but the principles by which these cells analyze faces are unknown. We found that middle face patch neurons detect and differentiate faces using a strategy that is both part based and holistic. Cells detected distinct constellations of face parts. Furthermore, cells were tuned to the geometry of facial features. Tuning was most often ramp-shaped, with a one-to-one mapping of feature magnitude to firing rate. Tuning amplitude depended on the presence of a whole, upright face and features were interpreted according to their position in a whole, upright face. Thus, cells in the middle face patch encode axes of a face space specialized for whole, upright faces
@article{freiwald_face_2009,
title = {A face feature space in the macaque temporal lobe.},
volume = {12},
doi = {10.1038/nn.2363},
abstract = {The ability of primates to effortlessly recognize faces has been attributed to the existence of specialized face areas. One such area, the macaque middle face patch, consists almost entirely of cells that are selective for faces, but the principles by which these cells analyze faces are unknown. We found that middle face patch neurons detect and differentiate faces using a strategy that is both part based and holistic. Cells detected distinct constellations of face parts. Furthermore, cells were tuned to the geometry of facial features. Tuning was most often ramp-shaped, with a one-to-one mapping of feature magnitude to firing rate. Tuning amplitude depended on the presence of a whole, upright face and features were interpreted according to their position in a whole, upright face. Thus, cells in the middle face patch encode axes of a face space specialized for whole, upright faces},
language = {eng},
number = {9},
journal = {Nat Neurosci},
author = {Freiwald, Winrich A and Tsao, Doris Y and Livingstone, Margaret S},
year = {2009},
pmid = {19668199},
note = {Place: United States
ISBN: 1546-1726},
keywords = {Action Potentials, Analysis of Variance, Animals, Face, Macaca mulatta, Magnetic Resonance Imaging, Male, Microelectrodes, Neurons, Photic Stimulation, Temporal Lobe, Time Factors, Visual Perception, research support, n.i.h., extramural, research support, non-u.s. gov't},
pages = {1187--1196},
}Long-term use of antidepressants for depressive disorders and the risk of diabetes mellitus. Andersohn, F., Schade, R., Suissa, S., & Garbe, E. The American Journal of Psychiatry, 166(5):591--598, May, 2009.
doi abstract bibtex
doi abstract bibtex
OBJECTIVE: Use of antidepressants has been reported to cause considerable weight gain. The aim of this study was to assess the risk of diabetes mellitus associated with antidepressant treatment and to examine whether the risk is influenced by treatment duration or daily dose. METHOD: This was a nested case-control study in a cohort of 165,958 patients with depression who received at least one new prescription for an antidepressant between January 1, 1990, and June 30, 2005. Data were from from the U.K. General Practice Research Database. Patients were at least 30 years of age and without diabetes at cohort entry. RESULTS: A total of 2,243 cases of incident diabetes mellitus and 8,963 matched comparison subjects were identified. Compared with no use of antidepressants during the past 2 years, recent long-term use (\textgreater24 months) of antidepressants in moderate to high daily doses was associated with an increased risk of diabetes (incidence rate ratio=1.84, 95% CI=1.35-2.52). The magnitude of the risk was similar for long-term use of moderate to high daily doses of tricyclic antidepressants (incidence rate ratio=1.77, 95% CI=1.21-2.59) and selective serotonin reuptake inhibitors (incidence rate ratio=2.06, 95% CI=1.20-3.52). Treatment for shorter periods or with lower daily doses was not associated with an increased risk. CONCLUSIONS: Long-term use of antidepressants in at least moderate daily doses was associated with an increased risk of diabetes. This association was observed for both tricyclic antidepressants and selective serotonin reuptake inhibitors.
@article{andersohn_long-term_2009,
title = {Long-term use of antidepressants for depressive disorders and the risk of diabetes mellitus},
volume = {166},
issn = {1535-7228},
doi = {10.1176/appi.ajp.2008.08071065},
abstract = {OBJECTIVE: Use of antidepressants has been reported to cause considerable weight gain. The aim of this study was to assess the risk of diabetes mellitus associated with antidepressant treatment and to examine whether the risk is influenced by treatment duration or daily dose.
METHOD: This was a nested case-control study in a cohort of 165,958 patients with depression who received at least one new prescription for an antidepressant between January 1, 1990, and June 30, 2005. Data were from from the U.K. General Practice Research Database. Patients were at least 30 years of age and without diabetes at cohort entry.
RESULTS: A total of 2,243 cases of incident diabetes mellitus and 8,963 matched comparison subjects were identified. Compared with no use of antidepressants during the past 2 years, recent long-term use ({\textgreater}24 months) of antidepressants in moderate to high daily doses was associated with an increased risk of diabetes (incidence rate ratio=1.84, 95\% CI=1.35-2.52). The magnitude of the risk was similar for long-term use of moderate to high daily doses of tricyclic antidepressants (incidence rate ratio=1.77, 95\% CI=1.21-2.59) and selective serotonin reuptake inhibitors (incidence rate ratio=2.06, 95\% CI=1.20-3.52). Treatment for shorter periods or with lower daily doses was not associated with an increased risk.
CONCLUSIONS: Long-term use of antidepressants in at least moderate daily doses was associated with an increased risk of diabetes. This association was observed for both tricyclic antidepressants and selective serotonin reuptake inhibitors.},
language = {eng},
number = {5},
journal = {The American Journal of Psychiatry},
author = {Andersohn, Frank and Schade, René and Suissa, Samy and Garbe, Edeltraut},
month = may,
year = {2009},
pmid = {19339356},
keywords = {Amitriptyline, Antidepressive Agents, Tricyclic, Body Mass Index, Case-Control Studies, Cyclohexanols, Depressive Disorder, Female, Fluvoxamine, Great Britain, Humans, Male, Middle Aged, Paroxetine, Risk Factors, Serotonin Uptake Inhibitors, Time Factors, diabetes mellitus, incidence},
pages = {591--598}
}Structured variability of muscle activations supports the minimal intervention principle of motor control. Valero-Cuevas, J, F., Venkadesan, M., & Todorov, E. Journal of neurophysiology, 102:59-68, 2009 Jul, 2009.
Paper doi abstract bibtex
Paper doi abstract bibtex Numerous observations of structured motor variability indicate that the sensorimotor system preferentially controls task-relevant parameters while allowing task-irrelevant ones to fluctuate. Optimality models show that controlling a redundant musculo-skeletal system in this manner meets task demands while minimizing control effort. Although this line of inquiry has been very productive, the data are mostly behavioral with no direct physiological evidence on the level of muscle or neural activity. Furthermore, biomechanical coupling, signal-dependent noise, and alternative causes of trial-to-trial variability confound behavioral studies. Here we address those confounds and present evidence that the nervous system preferentially controls task-relevant parameters on the muscle level. We asked subjects to produce vertical fingertip force vectors of prescribed constant or time-varying magnitudes while maintaining a constant finger posture. We recorded intramuscular electromyograms (EMGs) simultaneously from all seven index finger muscles during this task. The experiment design and selective fine-wire muscle recordings allowed us to account for a median of 91% of the variance of fingertip forces given the EMG signals. By analyzing muscle coordination in the seven-dimensional EMG signal space, we find that variance-per-dimension is consistently smaller in the task-relevant subspace than in the task-irrelevant subspace. This first direct physiological evidence on the muscle level for preferential control of task-relevant parameters strongly suggest the use of a neural control strategy compatible with the principle of minimal intervention. Additionally, variance is nonnegligible in all seven dimensions, which is at odds with the view that muscle activation patterns are composed from a small number of synergies.
@article{ 71,
title = {Structured variability of muscle activations supports the minimal intervention principle of motor control.},
journal = {Journal of neurophysiology},
volume = {102},
year = {2009},
month = {2009 Jul},
pages = {59-68},
abstract = {Numerous observations of structured motor variability indicate that the sensorimotor system preferentially controls task-relevant parameters while allowing task-irrelevant ones to fluctuate. Optimality models show that controlling a redundant musculo-skeletal system in this manner meets task demands while minimizing control effort. Although this line of inquiry has been very productive, the data are mostly behavioral with no direct physiological evidence on the level of muscle or neural activity. Furthermore, biomechanical coupling, signal-dependent noise, and alternative causes of trial-to-trial variability confound behavioral studies. Here we address those confounds and present evidence that the nervous system preferentially controls task-relevant parameters on the muscle level. We asked subjects to produce vertical fingertip force vectors of prescribed constant or time-varying magnitudes while maintaining a constant finger posture. We recorded intramuscular electromyograms (EMGs) simultaneously from all seven index finger muscles during this task. The experiment design and selective fine-wire muscle recordings allowed us to account for a median of 91% of the variance of fingertip forces given the EMG signals. By analyzing muscle coordination in the seven-dimensional EMG signal space, we find that variance-per-dimension is consistently smaller in the task-relevant subspace than in the task-irrelevant subspace. This first direct physiological evidence on the muscle level for preferential control of task-relevant parameters strongly suggest the use of a neural control strategy compatible with the principle of minimal intervention. Additionally, variance is nonnegligible in all seven dimensions, which is at odds with the view that muscle activation patterns are composed from a small number of synergies.},
keywords = {Adolescent, Adult, Biological, Biomechanics, Electromyography, Female, Fingers, Humans, Male, Models, Movement, Muscle, Muscle Contraction, Muscle Strength, Posture, Principal Component Analysis, Psychomotor Performance, Skeletal, Time Factors, Young Adult},
issn = {0022-3077},
doi = {10.1152/jn.90324.2008},
url = {http://jn.physiology.org/content/102/1/59.long},
author = {Valero-Cuevas, Francisco J and Venkadesan, Madhusudhan and Todorov, Emanuel}
}Ectopic Meis1 expression in the mouse limb bud alters P-D patterning in a Pbx1-independent manner. Mercader, N., Selleri, L., Criado, L., M., Pallares, P., Parras, C., Cleary, M., L., & Torres, M. The International journal of developmental biology, 53(8-10):1483-94, 1, 2009.
Paper Website abstract bibtex
Paper Website abstract bibtex During limb development, expression of the TALE homeobox transcription factor Meis1 is activated by retinoic acid in the proximal-most limb bud regions, which give rise to the upper forelimb and hindlimb. Early subdivision of the limb bud into proximal Meis-positive and distal Meis-negative domains is necessary for correct proximo-distal (P-D) limb development in the chick, since ectopic Meis1 overexpression abolishes distal limb structures, produces a proximal shift of limb identities along the P-D axis, and proximalizes distal limb cell affinity properties. To determine whether Meis activity is also required for P-D limb specification in mammals, we generated transgenic mice ectopically expressing Meis1 in the distal limb mesenchyme under the control of the Msx2 promoter. Msx2:Meis1 transgenic mice display altered P-D patterning and shifted P-D Hox gene expression domains, similar to those previously described for the chicken. Meis proteins function in cooperation with PBX factors, another TALE homeodomain subfamily. Meis-Pbx interaction is required for nuclear localization of both proteins in cell culture, and is important for their DNA-binding and transactivation efficiency. During limb development, Pbx1 nuclear expression correlates with the Meis expression domain, and Pbx1 has been proposed as the main Meis partner in this context; however, we found that Pbx1 deficiency did not modify the limb phenotype of Msx2:Meis1 mice. Our results indicate a conserved role of Meis activity in P-D specification of the tetrapod limb and suggest that Pbx function in this context is either not required or is provided by partners other than Pbx1.
@article{
title = {Ectopic Meis1 expression in the mouse limb bud alters P-D patterning in a Pbx1-independent manner.},
type = {article},
year = {2009},
identifiers = {[object Object]},
keywords = {Animals,Body Patterning,Body Patterning: genetics,Body Patterning: physiology,Embryo, Mammalian,Embryo, Mammalian: embryology,Embryo, Mammalian: metabolism,Gene Expression Regulation, Developmental,Homeodomain Proteins,Homeodomain Proteins: genetics,Homeodomain Proteins: metabolism,Homeodomain Proteins: physiology,Immunohistochemistry,In Situ Hybridization,Limb Buds,Limb Buds: embryology,Limb Buds: metabolism,Mice,Mice, Inbred C57BL,Mice, Transgenic,Neoplasm Proteins,Neoplasm Proteins: genetics,Neoplasm Proteins: metabolism,Neoplasm Proteins: physiology,Time Factors,Transcription Factors,Transcription Factors: genetics,Transcription Factors: metabolism,Transcription Factors: physiology},
pages = {1483-94},
volume = {53},
websites = {http://www.ncbi.nlm.nih.gov/pubmed/19247936},
month = {1},
id = {126d963a-2456-3fa6-94ca-b4f994d865d7},
created = {2016-04-08T12:19:35.000Z},
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profile_id = {994bc413-6766-31df-917a-32165aa30f6c},
group_id = {cec5aa9e-65e1-3c21-bc44-78fa6504020e},
last_modified = {2017-03-14T10:42:46.538Z},
read = {true},
starred = {false},
authored = {false},
confirmed = {true},
hidden = {false},
citation_key = {Mercader2009},
folder_uuids = {37786225-e8d4-483b-be04-dfc97f200748},
private_publication = {false},
abstract = {During limb development, expression of the TALE homeobox transcription factor Meis1 is activated by retinoic acid in the proximal-most limb bud regions, which give rise to the upper forelimb and hindlimb. Early subdivision of the limb bud into proximal Meis-positive and distal Meis-negative domains is necessary for correct proximo-distal (P-D) limb development in the chick, since ectopic Meis1 overexpression abolishes distal limb structures, produces a proximal shift of limb identities along the P-D axis, and proximalizes distal limb cell affinity properties. To determine whether Meis activity is also required for P-D limb specification in mammals, we generated transgenic mice ectopically expressing Meis1 in the distal limb mesenchyme under the control of the Msx2 promoter. Msx2:Meis1 transgenic mice display altered P-D patterning and shifted P-D Hox gene expression domains, similar to those previously described for the chicken. Meis proteins function in cooperation with PBX factors, another TALE homeodomain subfamily. Meis-Pbx interaction is required for nuclear localization of both proteins in cell culture, and is important for their DNA-binding and transactivation efficiency. During limb development, Pbx1 nuclear expression correlates with the Meis expression domain, and Pbx1 has been proposed as the main Meis partner in this context; however, we found that Pbx1 deficiency did not modify the limb phenotype of Msx2:Meis1 mice. Our results indicate a conserved role of Meis activity in P-D specification of the tetrapod limb and suggest that Pbx function in this context is either not required or is provided by partners other than Pbx1.},
bibtype = {article},
author = {Mercader, Nadia and Selleri, Licia and Criado, Luis Miguel and Pallares, Pilar and Parras, Carlos and Cleary, Michael L and Torres, Miguel},
journal = {The International journal of developmental biology},
number = {8-10}
}2008 (1)
Assessment of sediment contamination in Casco Bay, Maine, USA. Wade, T., L., Sweet, S., T., & Klein, A., G. Environmental pollution (Barking, Essex : 1987), 152(3):505-21, 4, 2008.
Website abstract bibtex
Website abstract bibtex The current status of contaminant concentrations in Casco Bay, decadal trends of these contaminants and changes in their geographical distribution are assessed using sediment samples collected approximately 10 years apart. In general, regulated contaminants appeared to be decreasing in concentration. Total PAH and dioxins/furans concentrations did not significantly change over this period. Total organochlorine pesticides, 4,4-DDE, 4,4-DDD, total DDT, PCB, tributyltin and total butyltin decreased in concentration. Trace element concentrations in sediments decreased at the majority of the sampling sites for chromium, nickel, and selenium while arsenic, cadmium, copper, lead, mercury, silver, and zinc remained relatively constant. None of the contaminants measured has increased by more than a factor of 2. Selected sites located in the Inner Bay, where concentrations are higher and new inputs were more likely, showed increased concentrations of contaminants. Most contaminants were not found at concentrations expected to adversely affect sediment biota based on ERL/ERM guidelines.
@article{
title = {Assessment of sediment contamination in Casco Bay, Maine, USA.},
type = {article},
year = {2008},
identifiers = {[object Object]},
keywords = {Aromatic,Aromatic: analysis,Chlorinated,Chlorinated: analysis,DDT,DDT: analysis,Dichlorodiphenyl Dichloroethylene,Dichlorodiphenyl Dichloroethylene: analysis,Dioxins,Dioxins: analysis,Environmental Monitoring,Environmental Monitoring: methods,Environmental Pollutants,Environmental Pollutants: analysis,Geologic Sediments,Geologic Sediments: chemistry,Hydrocarbons,Insecticides,Insecticides: analysis,Maine,Metals,Metals: analysis,Polychlorinated Biphenyls,Polychlorinated Biphenyls: analysis,Polycyclic Hydrocarbons,Time Factors,Trialkyltin Compounds,Trialkyltin Compounds: analysis},
pages = {505-21},
volume = {152},
websites = {http://www.ncbi.nlm.nih.gov/pubmed/17804129},
month = {4},
id = {d5329db2-aa6e-3cd2-9842-f8b9ce3cf389},
created = {2014-11-11T14:34:29.000Z},
accessed = {2014-11-11},
file_attached = {true},
profile_id = {03bdbf9c-0848-344e-95e3-9d552532f95c},
group_id = {3addd0f7-d578-34d3-be80-24022cc062a1},
last_modified = {2017-03-14T12:29:49.371Z},
read = {false},
starred = {false},
authored = {false},
confirmed = {true},
hidden = {false},
folder_uuids = {d000dcaa-1e0f-4184-a2c5-db979347585a},
private_publication = {false},
abstract = {The current status of contaminant concentrations in Casco Bay, decadal trends of these contaminants and changes in their geographical distribution are assessed using sediment samples collected approximately 10 years apart. In general, regulated contaminants appeared to be decreasing in concentration. Total PAH and dioxins/furans concentrations did not significantly change over this period. Total organochlorine pesticides, 4,4-DDE, 4,4-DDD, total DDT, PCB, tributyltin and total butyltin decreased in concentration. Trace element concentrations in sediments decreased at the majority of the sampling sites for chromium, nickel, and selenium while arsenic, cadmium, copper, lead, mercury, silver, and zinc remained relatively constant. None of the contaminants measured has increased by more than a factor of 2. Selected sites located in the Inner Bay, where concentrations are higher and new inputs were more likely, showed increased concentrations of contaminants. Most contaminants were not found at concentrations expected to adversely affect sediment biota based on ERL/ERM guidelines.},
bibtype = {article},
author = {Wade, Terry L. and Sweet, Stephen T. and Klein, Andrew G.},
journal = {Environmental pollution (Barking, Essex : 1987)},
number = {3}
}2007 (2)
Electroporation-based methods for in vivo, whole mount and primary culture analysis of zebrafish brain development. Hendricks, M. & Jesuthasan, S. Neural development, 2(March):6, January, 2007.
Paper doi abstract bibtex
Paper doi abstract bibtex BACKGROUND: Electroporation is a technique for the introduction of nucleic acids and other macromolecules into cells. In chick embryos it has been a particularly powerful technique for the spatial and temporal control of gene expression in developmental studies. Electroporation methods have also been reported for Xenopus, zebrafish, and mouse. RESULTS: We present a new protocol for zebrafish brain electroporation. Using a simple set-up with fixed spaced electrodes and microinjection equipment, it is possible to electroporate 50 to 100 embryos in 1 hour with no lethality and consistently high levels of transgene expression in numerous cells. Transfected cells in the zebrafish brain are amenable to in vivo time lapse imaging. Explants containing transfected neurons can be cultured for in vitro analysis. We also present a simple enzymatic method to isolate whole brains from fixed zebrafish for immunocytochemistry. CONCLUSION: Building on previously described methods, we have optimized several parameters to allow for highly efficient unilateral or bilateral transgenesis of a large number of cells in the zebrafish brain. This method is simple and provides consistently high levels of transgenesis for large numbers of embryos.
@article{Hendricks2007,
title = {Electroporation-based methods for in vivo, whole mount and primary culture analysis of zebrafish brain development.},
volume = {2},
issn = {1749-8104},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1838412&tool=pmcentrez&rendertype=abstract},
doi = {10.1186/1749-8104-2-6},
abstract = {BACKGROUND: Electroporation is a technique for the introduction of nucleic acids and other macromolecules into cells. In chick embryos it has been a particularly powerful technique for the spatial and temporal control of gene expression in developmental studies. Electroporation methods have also been reported for Xenopus, zebrafish, and mouse.
RESULTS: We present a new protocol for zebrafish brain electroporation. Using a simple set-up with fixed spaced electrodes and microinjection equipment, it is possible to electroporate 50 to 100 embryos in 1 hour with no lethality and consistently high levels of transgene expression in numerous cells. Transfected cells in the zebrafish brain are amenable to in vivo time lapse imaging. Explants containing transfected neurons can be cultured for in vitro analysis. We also present a simple enzymatic method to isolate whole brains from fixed zebrafish for immunocytochemistry.
CONCLUSION: Building on previously described methods, we have optimized several parameters to allow for highly efficient unilateral or bilateral transgenesis of a large number of cells in the zebrafish brain. This method is simple and provides consistently high levels of transgenesis for large numbers of embryos.},
number = {March},
urldate = {2013-09-06},
journal = {Neural development},
author = {Hendricks, Michael and Jesuthasan, Suresh},
month = jan,
year = {2007},
pmid = {17359546},
keywords = {\#nosource, Animals, Brain, Brain: embryology, Brain: growth \& development, Brain: surgery, Cell Culture Techniques, Cells, Cultured, Electroporation, Electroporation: instrumentation, Electroporation: methods, Embryo, Nonmammalian, Embryo, Nonmammalian: cytology, Embryo, Nonmammalian: embryology, Embryo, Nonmammalian: surgery, Microinjections, Microinjections: instrumentation, Microinjections: methods, Microscopy, Video, Microscopy, Video: methods, Molecular Biology, Molecular Biology: instrumentation, Molecular Biology: methods, Nucleic Acids, Nucleic Acids: pharmacology, Time Factors, Transfection, Transfection: instrumentation, Transfection: methods, Zebrafish, Zebrafish: embryology, Zebrafish: growth \& development, Zebrafish: surgery},
pages = {6},
}The neuropsychological effects of chronic methylphenidate on drug-naive boys with attention-deficit/hyperactivity disorder. Coghill, D. R, Rhodes, S. M, & Matthews, K. Biological Psychiatry, 62(9):954–962, 2007. Publisher: Section of Psychiatry and Behavioral Sciences, Division of Pathology and Neuroscience, University of Dundee, Ninewells Medical School, Dundee, United Kingdom. d.r.coghill@dundee.ac.uk
Paper abstract bibtex
Paper abstract bibtex BACKGROUND: The reported neuropsychological effects of methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD) are inconsistent. The assumed relationships between these neuropsychological effects and clinical efficacy have not been substantiated. We therefore investigated the effects of chronic MPH administration on neuropsychological functioning. METHODS: We conducted a 12-week, placebo-controlled, double-blinded, randomized, crossover trial (MPH .3 and .6 mg/kg/dose and placebo). Participants were 75 boys aged 7-15 years with ADHD. Neuropsychological performance was assessed with tests taken from the Cambridge Neuropsychological Test Automated Battery (CANTAB) battery and a GoNoGo task. RESULTS: Chronic MPH improved performance (p .05). GoNoGo performance improvements were the only neuropsychopharmacological changes associated with clinical response. Poor performance on the DMtS task was the sole baseline neuropsychological predictor of clinical response. CONCLUSIONS: Chronic MPH predominantly enhanced neuropsychological functioning on "recognition memory" component tasks with modest "executive" demands. Neuropsychological measures offer only modest contributions to the prediction of clinical responses to MPH in ADHD.
@article{coghill_neuropsychological_2007,
title = {The neuropsychological effects of chronic methylphenidate on drug-naive boys with attention-deficit/hyperactivity disorder},
volume = {62},
url = {http://dx.doi.org/10.1016/j.biopsych.2006.12.030},
abstract = {BACKGROUND: The reported neuropsychological effects of methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD) are inconsistent. The assumed relationships between these neuropsychological effects and clinical efficacy have not been substantiated. We therefore investigated the effects of chronic MPH administration on neuropsychological functioning. METHODS: We conducted a 12-week, placebo-controlled, double-blinded, randomized, crossover trial (MPH .3 and .6 mg/kg/dose and placebo). Participants were 75 boys aged 7-15 years with ADHD. Neuropsychological performance was assessed with tests taken from the Cambridge Neuropsychological Test Automated Battery (CANTAB) battery and a GoNoGo task. RESULTS: Chronic MPH improved performance (p .05). GoNoGo performance improvements were the only neuropsychopharmacological changes associated with clinical response. Poor performance on the DMtS task was the sole baseline neuropsychological predictor of clinical response. CONCLUSIONS: Chronic MPH predominantly enhanced neuropsychological functioning on "recognition memory" component tasks with modest "executive" demands. Neuropsychological measures offer only modest contributions to the prediction of clinical responses to MPH in ADHD.},
number = {9},
journal = {Biological Psychiatry},
author = {Coghill, David R and Rhodes, Sinéad M and Matthews, Keith},
year = {2007},
note = {Publisher: Section of Psychiatry and Behavioral Sciences, Division of Pathology and Neuroscience, University of Dundee, Ninewells Medical School, Dundee, United Kingdom. d.r.coghill@dundee.ac.uk},
keywords = {adolescent, association learning, association learning drug effects, attention deficit disorder with hyperactivity, attention deficit disorder with hyperactivity dru, attention deficit disorder with hyperactivity phy, central nervous system stimulants, central nervous system stimulants administration, child, choice behavior, choice behavior drug effects, cross over studies, dose response relationship, double blind method, drug, drug administration routes, humans, male, methylphenidate, methylphenidate administration \& dosage, neuropsychological tests, neuropsychological tests statistics \& numerical d, predictive value tests, principal component analysis, problem solving, problem solving drug effects, reaction time, reaction time drug effects, recognition (psychology), recognition (psychology) drug effects, time factors},
pages = {954--962},
}2006 (4)
Convergent validity of six methods to assess physical activity in daily life. Macfarlane, D. J, Lee, C. C Y, Ho, E. Y K, Chan, K L, & Chan, D. Journal of Applied Physiology (Bethesda, Md.: 1985), 101(5):1328–1334, November, 2006.
Paper doi abstract bibtex
Paper doi abstract bibtex The purpose was to examine the agreement (convergent validity) between six common measures of habitual physical activity to estimate durations of light, moderate, vigorous, and total activity in a range of free-living individuals. Over 7 consecutive days, 49 ethnic Chinese (30 men, 19 women), aged 15-55 yr, wore a Polar heart rate monitor, a uniaxial MTI, and triaxial Tritrac accelerometer, plus a Yamax pedometer for \textgreater or = 600 min/day. They also completed a daily physical activity log and on day 8 a Chinese version of the 7-day International Physical Activity Questionnaire. At each level of activity, there was good agreement between the two questionnaire-derived instruments and the two accelerometry-derived instruments, but wide variation across different instruments, with two- to fourfold differences in mean durations often seen. The heart rate monitor overestimated light activity and underestimated moderate activity compared with all other measures. Spearman correlation coefficients were low to moderate (0.2-0.5) across most measures of activity, with the pedometer showing correlations with total activity that were often superior to the other movement sensors. We conclude that, with the use of commonly accepted cut points for defining light, moderate, vigorous, and total activity, little convergent validity across the instruments was evident, suggesting these measures are sampling different levels of habitual physical activity and care is needed when comparing their results. To provide a more stable comparison of activity among different people, across studies, or against accepted physical activity promotion guidelines, further work is needed to fine tune the different cut points across a range of common activity monitors to provide more consistent results during free-living conditions.
@article{macfarlane_convergent_2006,
title = {Convergent validity of six methods to assess physical activity in daily life},
volume = {101},
issn = {8750-7587},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16825525},
doi = {10.1152/japplphysiol.00336.2006},
abstract = {The purpose was to examine the agreement (convergent validity) between six common measures of habitual physical activity to estimate durations of light, moderate, vigorous, and total activity in a range of free-living individuals. Over 7 consecutive days, 49 ethnic Chinese (30 men, 19 women), aged 15-55 yr, wore a Polar heart rate monitor, a uniaxial MTI, and triaxial Tritrac accelerometer, plus a Yamax pedometer for {\textgreater} or = 600 min/day. They also completed a daily physical activity log and on day 8 a Chinese version of the 7-day International Physical Activity Questionnaire. At each level of activity, there was good agreement between the two questionnaire-derived instruments and the two accelerometry-derived instruments, but wide variation across different instruments, with two- to fourfold differences in mean durations often seen. The heart rate monitor overestimated light activity and underestimated moderate activity compared with all other measures. Spearman correlation coefficients were low to moderate (0.2-0.5) across most measures of activity, with the pedometer showing correlations with total activity that were often superior to the other movement sensors. We conclude that, with the use of commonly accepted cut points for defining light, moderate, vigorous, and total activity, little convergent validity across the instruments was evident, suggesting these measures are sampling different levels of habitual physical activity and care is needed when comparing their results. To provide a more stable comparison of activity among different people, across studies, or against accepted physical activity promotion guidelines, further work is needed to fine tune the different cut points across a range of common activity monitors to provide more consistent results during free-living conditions.},
number = {5},
urldate = {2010-02-17},
journal = {Journal of Applied Physiology (Bethesda, Md.: 1985)},
author = {Macfarlane, Duncan J and Lee, Cherry C Y and Ho, Edmond Y K and Chan, K L and Chan, Dionise},
month = nov,
year = {2006},
pmid = {16825525},
keywords = {Activities of Daily Living, Adolescent, Adult, China, Female, Heart Rate, Humans, Male, Middle Aged, Monitoring, Ambulatory, Motor Activity, Questionnaires, Reproducibility of Results, Time Factors},
pages = {1328--1334},
}Raeding wrods with jubmled lettres: there is a cost. Rayner, K., White, S. J, Johnson, R. L, & Liversedge, S. P Psychol Sci, 17(3):192-3, 2006.
doi bibtex
doi bibtex
@Article{Rayner2006,
author = {Keith Rayner and Sarah J White and Rebecca L Johnson and Simon P Liversedge},
journal = {Psychol Sci},
title = {Raeding wrods with jubmled lettres: there is a cost.},
year = {2006},
number = {3},
pages = {192-3},
volume = {17},
doi = {10.1111/j.1467-9280.2006.01684.x},
keywords = {Comprehension, Extramural, Eye Movements, Humans, N.I.H., Non-U.S. Gov't, Pattern Recognition, Reading, Research Support, Space Perception, Students, Time Factors, Visual, Visual Perception, 16507057},
}Delayed enhancement MR imaging: utility in myocardial assessment. Vogel-Claussen, J., Rochitte, C. E., Wu, K. C., Kamel, I. R., Foo, T. K., Lima, J. A. C., & Bluemke, D. A. Radiographics: A Review Publication of the Radiological Society of North America, Inc, 26(3):795–810, June, 2006.
doi abstract bibtex
doi abstract bibtex
Use of magnetic resonance (MR) imaging for diagnosis of cardiac diseases and treatment monitoring is expanding. Delayed myocardial enhancement MR imaging is performed after administration of paramagnetic contrast agents and is used for a growing number of clinical applications. This technique was developed primarily for characterization of myocardial scarring after myocardial infarction. On delayed enhancement MR images, scarring or fibrosis appears as an area of high signal intensity that is typically subendocardial or transmural in a coronary artery distribution. However, delayed myocardial enhancement is not specific for myocardial infarction and can occur in a variety of other disorders, such as inflammatory or infectious diseases of the myocardium, cardiomyopathy, cardiac neoplasms, and congenital or genetic cardiac conditions, as well as after cardiac interventions. In nonischemic myocardial disease, the delayed enhancement usually does not occur in a coronary artery distribution and is often midwall rather than subendocardial or transmural. Therefore, the patient's clinical history is critical in the evaluation of delayed myocardial enhancement MR images.
@article{vogel-claussen_delayed_2006,
title = {Delayed enhancement {MR} imaging: utility in myocardial assessment},
volume = {26},
issn = {1527-1323},
shorttitle = {Delayed enhancement {MR} imaging},
doi = {10.1148/rg.263055047},
abstract = {Use of magnetic resonance (MR) imaging for diagnosis of cardiac diseases and treatment monitoring is expanding. Delayed myocardial enhancement MR imaging is performed after administration of paramagnetic contrast agents and is used for a growing number of clinical applications. This technique was developed primarily for characterization of myocardial scarring after myocardial infarction. On delayed enhancement MR images, scarring or fibrosis appears as an area of high signal intensity that is typically subendocardial or transmural in a coronary artery distribution. However, delayed myocardial enhancement is not specific for myocardial infarction and can occur in a variety of other disorders, such as inflammatory or infectious diseases of the myocardium, cardiomyopathy, cardiac neoplasms, and congenital or genetic cardiac conditions, as well as after cardiac interventions. In nonischemic myocardial disease, the delayed enhancement usually does not occur in a coronary artery distribution and is often midwall rather than subendocardial or transmural. Therefore, the patient's clinical history is critical in the evaluation of delayed myocardial enhancement MR images.},
language = {eng},
number = {3},
journal = {Radiographics: A Review Publication of the Radiological Society of North America, Inc},
author = {Vogel-Claussen, Jens and Rochitte, Carlos E. and Wu, Katherine C. and Kamel, Ihab R. and Foo, Thomas K. and Lima, João A. C. and Bluemke, David A.},
month = jun,
year = {2006},
pmid = {16702455},
keywords = {Cardiomyopathies, Contrast Media, Gadolinium DTPA, Humans, Image Enhancement, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Practice Guidelines as Topic, Practice Patterns, Physicians', Time Factors, Ventricular Dysfunction, Left},
pages = {795--810},
}Factors associated with perceived exertion and estimated time limit at lactate threshold. Garcin M, Mille-Hamard L, Duhamel A, Boudin F, Reveillere C, Billat V, & Lhermitte M Percept. Mot. Skills, 103:51-66, 2006.
Paper doi bibtex
Paper doi bibtex @article{garcin_m_factors_2006,
title = {Factors associated with perceived exertion and estimated time limit at lactate threshold},
volume = {103},
issn = {0031-5125},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17037643},
DOI = {10.2466/PMS.103.1.51-66},
Language = {English},
Journal = {Percept. Mot. Skills},
author = {{Garcin M} and {Mille-Hamard L} and {Duhamel A} and {Boudin F} and {Reveillere C} and {Billat V} and {Lhermitte M}},
year = {2006},
keywords = {Adaptation, Psychological, Adult, Anxiety Disorders/diagnosis, Attitude*, Feeding Behavior, Feeding and Eating Disorders/diagnosis, Female, Heart Rate/physiology, Humans, Lactic Acid/blood, Lactic Acid/metabolism*, Male, Muscle, Skeletal/metabolism*, Nutritional Status, Personality Inventory, Physical Exertion*, Quality of Life/psychology, Running, Surveys and Questionnaires, Time Factors},
pages = {51-66}
}2005 (6)
Effects of compulsory treatment orders on time to hospital readmission. Frank, D., Perry, J. C., Kean, D., Sigman, M., & Geagea, K. Psychiatric Services (Washington, D.C.), 56(7):867–869, July, 2005.
doi abstract bibtex
doi abstract bibtex
To evaluate the effect of compulsory community treatment orders on subsequent time out of the hospital, the authors studied the admission dates of psychotic patients who had repeated hospitalizations in Quebec, Canada, and divided each admission according to its time in relation to the index admission, during which the judicial order was obtained. The data were stratified by type of admission (early, preindex, index, or postindex), and the hypothesis tested was that the median time to readmission would be greatest for the index admission. The hypothesis was confirmed, supporting previous findings that judicial orders that mandate severely ill psychotic patients to undergo compulsory community treatment are associated with decreased time spent in the hospital and thus increased personal freedom.
@article{frank_effects_2005,
title = {Effects of compulsory treatment orders on time to hospital readmission},
volume = {56},
issn = {1075-2730},
doi = {10.1176/appi.ps.56.7.867},
abstract = {To evaluate the effect of compulsory community treatment orders on subsequent time out of the hospital, the authors studied the admission dates of psychotic patients who had repeated hospitalizations in Quebec, Canada, and divided each admission according to its time in relation to the index admission, during which the judicial order was obtained. The data were stratified by type of admission (early, preindex, index, or postindex), and the hypothesis tested was that the median time to readmission would be greatest for the index admission. The hypothesis was confirmed, supporting previous findings that judicial orders that mandate severely ill psychotic patients to undergo compulsory community treatment are associated with decreased time spent in the hospital and thus increased personal freedom.},
language = {eng},
number = {7},
journal = {Psychiatric Services (Washington, D.C.)},
author = {Frank, Daniel and Perry, J. Christopher and Kean, Dana and Sigman, Maxine and Geagea, Khalil},
month = jul,
year = {2005},
pmid = {16020822},
keywords = {Adult, Aged, Aged, 80 and over, Commitment of Mentally Ill, Community Mental Health Services, Female, Follow-Up Studies, Hospitalization, Humans, Male, Mental Disorders, Middle Aged, Patient Admission, Quebec, Time Factors, Treatment Outcome},
pages = {867--869},
}Proliferation, migration, neuronal differentiation, and long-term survival of new cells in the adult zebrafish brain. Zupanc, G. K H, Hinsch, K., & Gage, F. H The Journal of comparative neurology, 488(3):290–319, August, 2005.
Paper doi abstract bibtex
Paper doi abstract bibtex In contrast to mammals, fish exhibit an enormous potential to produce new cells in the adult brain. By labeling mitotically dividing cells with 5-bromo-2'-deoxyuridine (BrdU), we have characterized the development of these cells in the zebrafish (Danio rerio). Proliferation zones were located in specific regions of the olfactory bulb, dorsal telencephalon (including a region presumably homologous to the mammalian hippocampus), preoptic area, dorsal zone of the periventricular hypothalamus, optic tectum, torus longitudinalis, vagal lobe, parenchyma near the rhombencephalic ventricle, and in a region of the medulla oblongata lateral to the vagal motor nucleus, as well as in all three subdivisions of the cerebellum, the valvula cerebelli, the corpus cerebelli, and the lobus caudalis cerebelli. In the valvula cerebelli and the corpus cerebelli, the young cells migrated from their site of origin in the molecular layers to the corresponding granule cell layers. By contrast, in the lobus caudalis cerebelli and optic tectum, no indication of a migration of the newly generated cells over wider distances could be obtained. BrdU-labeled cells remained present in the brain over at least 292 days post-BrdU administration, indicating a long-term survival of a significant portion of the newly generated cells. The combination of BrdU immunohistochemistry with immunolabeling against the neural marker protein Hu, or with retrograde tracing, suggested a neuronal differentiation in a large portion of the young cells.
@article{Zupanc2005,
title = {Proliferation, migration, neuronal differentiation, and long-term survival of new cells in the adult zebrafish brain.},
volume = {488},
issn = {0021-9967},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15952170},
doi = {10.1002/cne.20571},
abstract = {In contrast to mammals, fish exhibit an enormous potential to produce new cells in the adult brain. By labeling mitotically dividing cells with 5-bromo-2'-deoxyuridine (BrdU), we have characterized the development of these cells in the zebrafish (Danio rerio). Proliferation zones were located in specific regions of the olfactory bulb, dorsal telencephalon (including a region presumably homologous to the mammalian hippocampus), preoptic area, dorsal zone of the periventricular hypothalamus, optic tectum, torus longitudinalis, vagal lobe, parenchyma near the rhombencephalic ventricle, and in a region of the medulla oblongata lateral to the vagal motor nucleus, as well as in all three subdivisions of the cerebellum, the valvula cerebelli, the corpus cerebelli, and the lobus caudalis cerebelli. In the valvula cerebelli and the corpus cerebelli, the young cells migrated from their site of origin in the molecular layers to the corresponding granule cell layers. By contrast, in the lobus caudalis cerebelli and optic tectum, no indication of a migration of the newly generated cells over wider distances could be obtained. BrdU-labeled cells remained present in the brain over at least 292 days post-BrdU administration, indicating a long-term survival of a significant portion of the newly generated cells. The combination of BrdU immunohistochemistry with immunolabeling against the neural marker protein Hu, or with retrograde tracing, suggested a neuronal differentiation in a large portion of the young cells.},
number = {3},
urldate = {2013-08-16},
journal = {The Journal of comparative neurology},
author = {Zupanc, Günther K H and Hinsch, Karen and Gage, Fred H},
month = aug,
year = {2005},
pmid = {15952170},
keywords = {\#nosource, Animals, Brain, Brain Mapping, Brain: cytology, Bromodeoxyuridine, Bromodeoxyuridine: metabolism, Calcium-Binding Protein, Vitamin D-Dependent, Calcium-Binding Protein, Vitamin D-Dependent: meta, Cell Count, Cell Count: methods, Cell Differentiation, Cell Differentiation: physiology, Cell Movement, Cell Movement: physiology, Cell Proliferation, Cell Survival, Cell Survival: physiology, Glial Fibrillary Acidic Protein, Glial Fibrillary Acidic Protein: metabolism, Hu Paraneoplastic Encephalomyelitis Antigens, Immunohistochemistry, Immunohistochemistry: methods, Nerve Tissue Proteins, Nerve Tissue Proteins: metabolism, Neurons, Neurons: cytology, RNA-Binding Proteins, RNA-Binding Proteins: metabolism, S100 Proteins, S100 Proteins: metabolism, Time Factors, Zebrafish, Zebrafish: physiology},
pages = {290--319},
}Protein tagging and detection with engineered self-assembling fragments of green fluorescent protein. Cabantous, S., Terwilliger, T. C, & Waldo, G. S Nature Biotechnology, 23(1):102--107, January, 2005.
Paper doi abstract bibtex
Paper doi abstract bibtex Existing protein tagging and detection methods are powerful but have drawbacks. Split protein tags can perturb protein solubility or may not work in living cells. Green fluorescent protein (GFP) fusions can misfold or exhibit altered processing. Fluorogenic biarsenical FLaSH or ReASH substrates overcome many of these limitations but require a polycysteine tag motif, a reducing environment and cell transfection or permeabilization. An ideal protein tag would be genetically encoded, would work both in vivo and in vitro, would provide a sensitive analytical signal and would not require external chemical reagents or substrates. One way to accomplish this might be with a split GFP, but the GFP fragments reported thus far are large and fold poorly, require chemical ligation or fused interacting partners to force their association, or require coexpression or co-refolding to produce detectable folded and fluorescent GFP. We have engineered soluble, self-associating fragments of GFP that can be used to tag and detect either soluble or insoluble proteins in living cells or cell lysates. The split GFP system is simple and does not change fusion protein solubility.
@article{cabantous_protein_2005,
title = {Protein tagging and detection with engineered self-assembling fragments of green fluorescent protein},
volume = {23},
issn = {1087-0156},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15580262},
doi = {10.1038/nbt1044},
abstract = {Existing protein tagging and detection methods are powerful but have drawbacks. Split protein tags can perturb protein solubility or may not work in living cells. Green fluorescent protein (GFP) fusions can misfold or exhibit altered processing. Fluorogenic biarsenical FLaSH or ReASH substrates overcome many of these limitations but require a polycysteine tag motif, a reducing environment and cell transfection or permeabilization. An ideal protein tag would be genetically encoded, would work both in vivo and in vitro, would provide a sensitive analytical signal and would not require external chemical reagents or substrates. One way to accomplish this might be with a split GFP, but the GFP fragments reported thus far are large and fold poorly, require chemical ligation or fused interacting partners to force their association, or require coexpression or co-refolding to produce detectable folded and fluorescent GFP. We have engineered soluble, self-associating fragments of GFP that can be used to tag and detect either soluble or insoluble proteins in living cells or cell lysates. The split GFP system is simple and does not change fusion protein solubility.},
number = {1},
urldate = {2009-05-03TZ},
journal = {Nature Biotechnology},
author = {Cabantous, Stéphanie and Terwilliger, Thomas C and Waldo, Geoffrey S},
month = jan,
year = {2005},
pmid = {15580262},
keywords = {Amino Acid Motifs, Cysteine, Electrophoresis, Polyacrylamide Gel, Escherichia coli, Genetic Complementation Test, Green Fluorescent Proteins, Protein Binding, Protein Engineering, Protein Structure, Tertiary, Proteomics, Pyrobaculum, Recombinant Fusion Proteins, Sensitivity and Specificity, Solubility, Time Factors},
pages = {102--107}
}Prognostic impact of positive surgical margins in surgically treated prostate cancer: multi-institutional assessment of 5831 patients. Karakiewicz, P. I., Eastham, J. A., Graefen, M., Cagiannos, I., Stricker, P. D., Klein, E., Cangiano, T., Schröder, F. H., Scardino, P. T., & Kattan, M. W. Urology, 66(6):1245–1250, December, 2005.
doi abstract bibtex
doi abstract bibtex
OBJECTIVES: To assess the prognostic significance of a positive surgical margin in the radical prostatectomy specimen, and to test for the presence of statistically significant interactions between surgical margin status and select pathologic stage variables. METHODS: We combined prospectively collected data from 7816 consecutive patients treated with radical prostatectomy at eight institutions. The pretreatment serum prostate-specific antigen level, pathologic Gleason sum, surgical margin status (positive versus negative), presence of extracapsular extension, seminal vesicle involvement, and pelvic lymph node status were examined as predictors of the rate of biochemical progression in 5831 patients with complete records. RESULTS: In multivariate Cox regression models, a positive surgical margin was associated with a 3.7-fold greater risk of progression (P = 0.001). Moreover, a statistically significant interaction was found between surgical margin status and Gleason sum 7 to 10 (P = 0.008) and lymph node invasion (P \textless 0.001). CONCLUSIONS: The presence of a positive surgical margin in the radical prostatectomy specimen has an adverse effect on prognosis. The greatest risk of biochemical recurrence may be expected if a positive surgical margin is present with Gleason sum 7 to 10 disease or lymph node invasion.
@article{karakiewicz_prognostic_2005,
title = {Prognostic impact of positive surgical margins in surgically treated prostate cancer: multi-institutional assessment of 5831 patients},
volume = {66},
issn = {1527-9995},
shorttitle = {Prognostic impact of positive surgical margins in surgically treated prostate cancer},
doi = {10.1016/j.urology.2005.06.108},
abstract = {OBJECTIVES: To assess the prognostic significance of a positive surgical margin in the radical prostatectomy specimen, and to test for the presence of statistically significant interactions between surgical margin status and select pathologic stage variables.
METHODS: We combined prospectively collected data from 7816 consecutive patients treated with radical prostatectomy at eight institutions. The pretreatment serum prostate-specific antigen level, pathologic Gleason sum, surgical margin status (positive versus negative), presence of extracapsular extension, seminal vesicle involvement, and pelvic lymph node status were examined as predictors of the rate of biochemical progression in 5831 patients with complete records.
RESULTS: In multivariate Cox regression models, a positive surgical margin was associated with a 3.7-fold greater risk of progression (P = 0.001). Moreover, a statistically significant interaction was found between surgical margin status and Gleason sum 7 to 10 (P = 0.008) and lymph node invasion (P {\textless} 0.001).
CONCLUSIONS: The presence of a positive surgical margin in the radical prostatectomy specimen has an adverse effect on prognosis. The greatest risk of biochemical recurrence may be expected if a positive surgical margin is present with Gleason sum 7 to 10 disease or lymph node invasion.},
language = {eng},
number = {6},
journal = {Urology},
author = {Karakiewicz, Pierre I. and Eastham, James A. and Graefen, Markus and Cagiannos, Ilias and Stricker, Phillip D. and Klein, Eric and Cangiano, Thomas and Schröder, Fritz H. and Scardino, Peter T. and Kattan, Michael W.},
month = dec,
year = {2005},
pmid = {16360451},
keywords = {Disease-Free Survival, Follow-Up Studies, Humans, Male, Neoplasm Recurrence, Local, Neoplasm Staging, Prognosis, Prospective Studies, Prostatic Neoplasms, Time Factors},
pages = {1245--1250}
}Spatial variability of fine particle mass, components, and source contributions during the regional air pollution study in St. Louis. Kim, E., Hopke, P., K., Pinto, J., P., & Wilson, W., E. Environmental science & technology, 39(11):4172-9, 6, 2005.
Paper Website abstract bibtex
Paper Website abstract bibtex Community time-series epidemiology typically uses either 24-hour integrated particulate matter (PM) concentrations averaged across several monitors in a city or data obtained at a central monitoring site to relate PM concentrations to human health effects. If the day-to-day variations in 24-hour integrated concentrations differ substantially across an urban area (i.e., daily measurements at monitors at different locations are not highly correlated), then there is a significant potential for exposure misclassification in community time-series epidemiology. If the annual average concentration differs across an urban area, then there is a potential for exposure misclassification in epidemiologic studies that use annual averages (or multi-year averages) as an index of exposure across different cities. The spatial variability in PM2.5 (particulate matter < or = 2.5 microm in aerodynamic diameter), its elemental components, and the contributions from each source category at 10 monitoring sites in St. Louis, Missouri were characterized using the ambient PM2.5 compositional data set of the Regional Air Pollution Study (RAPS) based on the Regional Air Monitoring System (RAMS) conducted between 1975 and 1977. Positive matrix factorization (PMF) was applied to each ambient PM2.5 compositional data set to estimate the contributions from the source categories. The spatial distributions of components and source contributions to PM2.5 at the 10 sites were characterized using Pearson correlation coefficients and coefficients of divergence. Sulfur and PM2.5 are highly correlated elements between all of the site pairs Although the secondary sulfate is the most highly correlated and shows the smallest spatial variability, there is a factor of 1.7 difference in secondary sulfate contributions between the highest and lowest site on average. Motor vehicles represent the next most highly correlated source component. However, there is a factor of 3.6 difference in motor vehicle contributions between the highest and lowest sites. The contributions from point source categories are much more variable. For example, the contributions from incinerators show a difference of a factor of 12.5 between the sites with the lowest and highest contributions. This study demonstrates that the spatial distributions of elemental components of PM2.5 and contributions from source categories can be highly heterogeneous within a given airshed and thus, there is the potential for exposure misclassification when a limited number of ambient PM monitors are used to represent population-average ambient exposures.
@article{
title = {Spatial variability of fine particle mass, components, and source contributions during the regional air pollution study in St. Louis.},
type = {article},
year = {2005},
identifiers = {[object Object]},
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pages = {4172-9},
volume = {39},
websites = {http://www.ncbi.nlm.nih.gov/pubmed/15984797},
month = {6},
day = {1},
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abstract = {Community time-series epidemiology typically uses either 24-hour integrated particulate matter (PM) concentrations averaged across several monitors in a city or data obtained at a central monitoring site to relate PM concentrations to human health effects. If the day-to-day variations in 24-hour integrated concentrations differ substantially across an urban area (i.e., daily measurements at monitors at different locations are not highly correlated), then there is a significant potential for exposure misclassification in community time-series epidemiology. If the annual average concentration differs across an urban area, then there is a potential for exposure misclassification in epidemiologic studies that use annual averages (or multi-year averages) as an index of exposure across different cities. The spatial variability in PM2.5 (particulate matter < or = 2.5 microm in aerodynamic diameter), its elemental components, and the contributions from each source category at 10 monitoring sites in St. Louis, Missouri were characterized using the ambient PM2.5 compositional data set of the Regional Air Pollution Study (RAPS) based on the Regional Air Monitoring System (RAMS) conducted between 1975 and 1977. Positive matrix factorization (PMF) was applied to each ambient PM2.5 compositional data set to estimate the contributions from the source categories. The spatial distributions of components and source contributions to PM2.5 at the 10 sites were characterized using Pearson correlation coefficients and coefficients of divergence. Sulfur and PM2.5 are highly correlated elements between all of the site pairs Although the secondary sulfate is the most highly correlated and shows the smallest spatial variability, there is a factor of 1.7 difference in secondary sulfate contributions between the highest and lowest site on average. Motor vehicles represent the next most highly correlated source component. However, there is a factor of 3.6 difference in motor vehicle contributions between the highest and lowest sites. The contributions from point source categories are much more variable. For example, the contributions from incinerators show a difference of a factor of 12.5 between the sites with the lowest and highest contributions. This study demonstrates that the spatial distributions of elemental components of PM2.5 and contributions from source categories can be highly heterogeneous within a given airshed and thus, there is the potential for exposure misclassification when a limited number of ambient PM monitors are used to represent population-average ambient exposures.},
bibtype = {article},
author = {Kim, Eugene and Hopke, Philip K and Pinto, Joseph P and Wilson, William E},
journal = {Environmental science & technology},
number = {11}
}Towards a novel class of predictive microbial growth models. Van Impe, J., F., Poschet, F., Geeraerd, A., H., & Vereecken, K., M. International journal of food microbiology, 100(1-3):97-105, 4, 2005.
abstract bibtex
abstract bibtex
Food safety and quality are influenced by the presence (and possible proliferation) of pathogenic and spoilage microorganisms during the life cycle of the product (i.e., from the raw ingredients at the start of the production process until the moment of consumption). In order to simulate and predict microbial evolution in foods, mathematical models are developed in the field of predictive microbiology. In general, microbial growth is a self-limiting process, principally due to either (i) the exhaustion of one of the essential nutrients, and/or (ii) the accumulation of toxic products that inhibit growth. Nowadays, most mathematical models used in predictive microbiology do not explicitly incorporate this basic microbial knowledge. In this paper, a novel class of microbial growth models is proposed. In contrast with the currently used logistic type models, e.g., the model of Baranyi and Roberts [Baranyi, J., Roberts, T.A., 1994. A dynamic approach to predicting bacterial growth in food. International Journal of Food Microbiology 23, 277-294], the novel model class explicitly incorporates nutrient exhaustion and/or metabolic waste product effects. As such, this novel model prototype constitutes an elementary building block to be extended in a natural way towards, e.g., microbial interactions in co-cultures (mediated by metabolic products) and microbial growth in structured foods (influenced by, e.g., local substrate concentrations). While under certain conditions the mathematical equivalence with classical logistic type models is clear and results in equal fitting capacities and parameter estimation quality (see Poschet et al. [Poschet, F., Vereecken, K.M., Geeraerd, A.H., Nicolai, B.M., Van Impe, J.F., 2004. Analysis of a novel class of predictive microbial growth models and application to co-culture growth. International Journal of Food Microbiology, this issue] for a more elaborated analysis in this respect), the biological interpretability and extendability represent the main added value.
@article{
title = {Towards a novel class of predictive microbial growth models.},
type = {article},
year = {2005},
identifiers = {[object Object]},
keywords = {Bacteria,Bacteria: growth & development,Bacteria: metabolism,Coculture Techniques,Consumer Product Safety,Food Microbiology,Hydrogen-Ion Concentration,Logistic Models,Models, Biological,Models, Theoretical,Predictive Value of Tests,Temperature,Time Factors},
pages = {97-105},
volume = {100},
websites = {http://www.ncbi.nlm.nih.gov/pubmed/15854696},
month = {4},
day = {15},
id = {4819b5a2-8df1-3e62-9348-4fb5f9a90ddc},
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confirmed = {true},
hidden = {false},
abstract = {Food safety and quality are influenced by the presence (and possible proliferation) of pathogenic and spoilage microorganisms during the life cycle of the product (i.e., from the raw ingredients at the start of the production process until the moment of consumption). In order to simulate and predict microbial evolution in foods, mathematical models are developed in the field of predictive microbiology. In general, microbial growth is a self-limiting process, principally due to either (i) the exhaustion of one of the essential nutrients, and/or (ii) the accumulation of toxic products that inhibit growth. Nowadays, most mathematical models used in predictive microbiology do not explicitly incorporate this basic microbial knowledge. In this paper, a novel class of microbial growth models is proposed. In contrast with the currently used logistic type models, e.g., the model of Baranyi and Roberts [Baranyi, J., Roberts, T.A., 1994. A dynamic approach to predicting bacterial growth in food. International Journal of Food Microbiology 23, 277-294], the novel model class explicitly incorporates nutrient exhaustion and/or metabolic waste product effects. As such, this novel model prototype constitutes an elementary building block to be extended in a natural way towards, e.g., microbial interactions in co-cultures (mediated by metabolic products) and microbial growth in structured foods (influenced by, e.g., local substrate concentrations). While under certain conditions the mathematical equivalence with classical logistic type models is clear and results in equal fitting capacities and parameter estimation quality (see Poschet et al. [Poschet, F., Vereecken, K.M., Geeraerd, A.H., Nicolai, B.M., Van Impe, J.F., 2004. Analysis of a novel class of predictive microbial growth models and application to co-culture growth. International Journal of Food Microbiology, this issue] for a more elaborated analysis in this respect), the biological interpretability and extendability represent the main added value.},
bibtype = {article},
author = {Van Impe, J F and Poschet, F and Geeraerd, A H and Vereecken, K M},
journal = {International journal of food microbiology},
number = {1-3}
}2004 (10)
Modelling the recent common ancestry of all living humans. Rohde, D., L., Olson, S., & Chang, J., T. Nature, 431(7008):562-566, 2004.
Paper abstract bibtex
Paper abstract bibtex If a common ancestor of all living humans is defined as an individual who is a genealogical ancestor of all present-day people, the most recent common ancestor (MRCA) for a randomly mating population would have lived in the very recent past. However, the random mating model ignores essential aspects of population substructure, such as the tendency of individuals to choose mates from the same social group, and the relative isolation of geographically separated groups. Here we show that recent common ancestors also emerge from two models incorporating substantial population substructure. One model, designed for simplicity and theoretical insight, yields explicit mathematical results through a probabilistic analysis. A more elaborate second model, designed to capture historical population dynamics in a more realistic way, is analysed computationally through Monte Carlo simulations. These analyses suggest that the genealogies of all living humans overlap in remarkable ways in the recent past. In particular, the MRCA of all present-day humans lived just a few thousand years ago in these models. Moreover, among all individuals living more than just a few thousand years earlier than the MRCA, each present-day human has exactly the same set of genealogical ancestors.
@article{
title = {Modelling the recent common ancestry of all living humans},
type = {article},
year = {2004},
identifiers = {[object Object]},
keywords = {*Computer Simulation,*Pedigree,*Phylogeny,Emigration and Immigration,Female,Geography,Humans,Male,Monte Carlo Method,Population Density,Population Dynamics,Reproduction,Research Support, U.S. Gov't, P.H.S.,Time Factors},
pages = {562-566},
volume = {431},
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abstract = {If a common ancestor of all living humans is defined as an individual who is a genealogical ancestor of all present-day people, the most recent common ancestor (MRCA) for a randomly mating population would have lived in the very recent past. However, the random mating model ignores essential aspects of population substructure, such as the tendency of individuals to choose mates from the same social group, and the relative isolation of geographically separated groups. Here we show that recent common ancestors also emerge from two models incorporating substantial population substructure. One model, designed for simplicity and theoretical insight, yields explicit mathematical results through a probabilistic analysis. A more elaborate second model, designed to capture historical population dynamics in a more realistic way, is analysed computationally through Monte Carlo simulations. These analyses suggest that the genealogies of all living humans overlap in remarkable ways in the recent past. In particular, the MRCA of all present-day humans lived just a few thousand years ago in these models. Moreover, among all individuals living more than just a few thousand years earlier than the MRCA, each present-day human has exactly the same set of genealogical ancestors.},
bibtype = {article},
author = {Rohde, D L and Olson, S and Chang, J T},
journal = {Nature},
number = {7008}
}Animal behaviour: Coalition among male fiddler crabs. Backwell, P. R Y & Jennions, M. D Nature, 430(6998):417, 2004.
doi abstract bibtex
doi abstract bibtex
Until now, no compelling evidence has emerged from studies of animal territoriality to indicate that a resident will strategically help a neighbour to defend its territory against an intruder. We show here that territory-owning Australian fiddler crabs will judiciously assist other crabs in defending their neighbouring territories. This cooperation supports the prediction that it is sometimes less costly to assist a familiar neighbour than to renegotiate boundaries with a new, and possibly stronger, neighbour.
@Article{Backwell2004,
author = {Patricia R Y Backwell and Michael D Jennions},
journal = {Nature},
title = {Animal behaviour: {C}oalition among male fiddler crabs.},
year = {2004},
number = {6998},
pages = {417},
volume = {430},
abstract = {Until now, no compelling evidence has emerged from studies of animal
territoriality to indicate that a resident will strategically help
a neighbour to defend its territory against an intruder. We show
here that territory-owning Australian fiddler crabs will judiciously
assist other crabs in defending their neighbouring territories. This
cooperation supports the prediction that it is sometimes less costly
to assist a familiar neighbour than to renegotiate boundaries with
a new, and possibly stronger, neighbour.},
doi = {10.1038/430417a},
keywords = {Animals, Attention, Brain, Decision Making, Face, Female, Haplorhini, Housing, Humans, Magnetic Resonance Imaging, Male, Models, Neurological, Pattern Recognition, Visual, Photic Stimulation, Prefrontal Cortex, Research Support, Non-U.S. Gov't, U.S. Gov't, P.H.S., Visual Perception, Choice Behavior, Cognition, Dopamine, Learning, Schizophrenia, Substance-Related Disorders, Generalization (Psychology), Motor Skills, Non-P.H.S., Nerve Net, Neuronal Plasticity, Perception, Cerebral Cortex, Memory, Neurons, Sound Localization, Synapses, Synaptic Transmission, Neural Pathways, Non-, Acoustic Stimulation, Adult, Age of Onset, Aging, Blindness, Child, Preschool, Infant, Newborn, Pitch Perception, Analysis of Variance, Animal Welfare, Laboratory, Behavior, Animal, Hybridization, Genetic, Maze Learning, Mice, Inbred C57BL, Inbred DBA, Phenotype, Reproducibility of Results, Darkness, Deafness, Finches, Sleep, Sound, Sunlight, Time Factors, Vocalization, Energy Metabolism, Evolution, Fossils, History, Ancient, Hominidae, Biological, Physical Endurance, Running, Skeleton, Walking, Acoustics, Auditory Perception, Cues, Discrimination Learning, Pair Bond, Social Behavior, Songbirds, Adolescent, England, Habituation (Psychophysiology), Korea, Language, Semantics, Vocabulary, Action Potentials, Hippocampus, Pyramidal Cells, Rats, Rotation, Australia, Brachyura, Cooperative Behavior, Logistic Models, Territoriality, 15269757},
}Recalibration of temporal order perception by exposure to audio-visual asynchrony. Vroomen, J., Keetels, M., de Gelder, B., & Bertelson, P. Brain Res Cogn Brain Res, 22(1):32-5, 2004.
doi abstract bibtex
doi abstract bibtex
The perception of simultaneity between auditory and visual information is of crucial importance for maintaining a coordinated representation of a multisensory event. Here we show that the perceptual system is able to adaptively recalibrate itself to audio-visual temporal asynchronies. Participants were exposed to a train of sounds and light flashes with a constant time lag ranging from -200 (sound first) to +200 ms (light first). Following this exposure, a temporal order judgement (TOJ) task was performed in which a sound and light were presented with a stimulus onset asynchrony (SOA) chosen from 11 values between -240 and +240 ms. Participants either judged whether the sound or the light was presented first, or whether the sound and light were presented simultaneously or successively. The point of subjective simultaneity (PSS) was, in both cases, shifted in the direction of the exposure lag, indicative of recalibration.
@Article{Vroomen2004,
author = {Jean Vroomen and Mirjam Keetels and Beatrice de Gelder and Paul Bertelson},
journal = {Brain Res Cogn Brain Res},
title = {Recalibration of temporal order perception by exposure to audio-visual asynchrony.},
year = {2004},
number = {1},
pages = {32-5},
volume = {22},
abstract = {The perception of simultaneity between auditory and visual information
is of crucial importance for maintaining a coordinated representation
of a multisensory event. Here we show that the perceptual system
is able to adaptively recalibrate itself to audio-visual temporal
asynchronies. Participants were exposed to a train of sounds and
light flashes with a constant time lag ranging from -200 (sound first)
to +200 ms (light first). Following this exposure, a temporal order
judgement (TOJ) task was performed in which a sound and light were
presented with a stimulus onset asynchrony (SOA) chosen from 11 values
between -240 and +240 ms. Participants either judged whether the
sound or the light was presented first, or whether the sound and
light were presented simultaneously or successively. The point of
subjective simultaneity (PSS) was, in both cases, shifted in the
direction of the exposure lag, indicative of recalibration.},
doi = {10.1016/j.cogbrainres.2004.07.003},
keywords = {Acoustic Stimulation, Analysis of Variance, Auditory Perception, Comparative Study, Humans, Judgment, Photic Stimulation, Reaction Time, Time Factors, Time Perception, Visual Perception, 15561498},
}High prevalence of knee osteoarthritis, pain, and functional limitations in female soccer players twelve years after anterior cruciate ligament injury. Lohmander, L. S., Ostenberg, A., Englund, M., & Roos, H. Arthritis and Rheumatism, 50(10):3145–3152, October, 2004.
Paper doi abstract bibtex
Paper doi abstract bibtex OBJECTIVE: To determine the prevalence of radiographic knee osteoarthritis (OA) as well as knee-related symptoms and functional limitations in female soccer players 12 years after an anterior cruciate ligament (ACL) injury. METHODS: Female soccer players who sustained an ACL injury 12 years earlier were examined with standardized weight-bearing knee radiography and 2 self-administered patient questionnaires, the Knee Injury and Osteoarthritis Outcome Score questionnaire and the Short Form 36-item health survey. Joint space narrowing and osteophytes were graded according to the radiographic atlas of the Osteoarthritis Research Society International. The cutoff value to define radiographic knee OA approximated a Kellgren/Lawrence grade of 2. RESULTS: Of the available cohort of 103 female soccer players, 84 (82%) answered the questionnaires and 67 (65%) consented to undergo knee radiography. The mean age at assessment was 31 years (range 26-40 years) and mean body mass index was 23 kg/m2 (range 18-40 kg/m2). Fifty-five women (82%) had radiographic changes in their index knee, and 34 (51%) fulfilled the criterion for radiographic knee OA. Of the subjects answering the questionnaires, 63 (75%) reported having symptoms affecting their knee-related quality of life, and 28 (42%) were considered to have symptomatic radiographic knee OA. Slightly more than 60% of the players had undergone reconstructive surgery of the ACL. Using multivariate analyses, surgical reconstruction was found to have no significant influence on knee symptoms. CONCLUSION: A very high prevalence of radiographic knee OA, pain, and functional limitations was observed in young women who sustained an ACL tear during soccer play 12 years earlier. These findings constitute a strong rationale to direct increased efforts toward prevention and better treatment of knee injury.
@article{lohmander_high_2004,
title = {High prevalence of knee osteoarthritis, pain, and functional limitations in female soccer players twelve years after anterior cruciate ligament injury.},
volume = {50},
issn = {0004-3591},
url = {http://dx.doi.org/10.1002/art.20589},
doi = {10.1002/art.20589},
abstract = {OBJECTIVE: To determine the prevalence of radiographic knee osteoarthritis (OA) as well as knee-related symptoms and functional limitations in female soccer players 12 years after an anterior cruciate ligament (ACL) injury.
METHODS: Female soccer players who sustained an ACL injury 12 years earlier were examined with standardized weight-bearing knee radiography and 2 self-administered patient questionnaires, the Knee Injury and Osteoarthritis Outcome Score questionnaire and the Short Form 36-item health survey. Joint space narrowing and osteophytes were graded according to the radiographic atlas of the Osteoarthritis Research Society International. The cutoff value to define radiographic knee OA approximated a Kellgren/Lawrence grade of 2.
RESULTS: Of the available cohort of 103 female soccer players, 84 (82\%) answered the questionnaires and 67 (65\%) consented to undergo knee radiography. The mean age at assessment was 31 years (range 26-40 years) and mean body mass index was 23 kg/m2 (range 18-40 kg/m2). Fifty-five women (82\%) had radiographic changes in their index knee, and 34 (51\%) fulfilled the criterion for radiographic knee OA. Of the subjects answering the questionnaires, 63 (75\%) reported having symptoms affecting their knee-related quality of life, and 28 (42\%) were considered to have symptomatic radiographic knee OA. Slightly more than 60\% of the players had undergone reconstructive surgery of the ACL. Using multivariate analyses, surgical reconstruction was found to have no significant influence on knee symptoms.
CONCLUSION: A very high prevalence of radiographic knee OA, pain, and functional limitations was observed in young women who sustained an ACL tear during soccer play 12 years earlier. These findings constitute a strong rationale to direct increased efforts toward prevention and better treatment of knee injury.},
language = {eng},
number = {10},
journal = {Arthritis and Rheumatism},
author = {Lohmander, L. S. and Ostenberg, A. and Englund, M. and Roos, H.},
month = oct,
year = {2004},
pmid = {15476248},
keywords = {Adult, Aged, Anterior Cruciate Ligament, Female, Humans, Knee, Middle Aged, Multivariate Analysis, Osteoarthritis, Knee, Pain, Prevalence, Quality of Life, Soccer, Surveys and Questionnaires, Time Factors},
pages = {3145--3152},
}Violence in an urban community from the perspective of an accident and emergency department: a two-year prospective study. Steen, K. & Hunskaar, S. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 10(2):CR75–79, February, 2004.
abstract bibtex
abstract bibtex
BACKGROUND: Information about violence in a given community is usually based on crime statistics. The aim of this study was to explore violence in an urban community from the perspective of an accident and emergency department. MATERIAL/METHODS: All assault victims treated at the Bergen Accident and Emergency Department (AED) during a two-year period (1994-1996) were prospectively registered, and data were collected about the patients and the assault incidents. To assess the proportion of unrecognized assault victims treated at the AED, an anonymous questionnaire was sent to all adult patients (first-time consultations) who visited the AED during a ten-day period in 1997. RESULTS: 1803 assault victims were registered, 433 of whom (24%) were females. Most of the victims were young men assaulted at public locations, under the influence of alcohol, often by unknown attackers, and frequently feeling that the attack was unprovoked (and thus defined as street violence). Few victims of child abuse or elder abuse were identified. About 40% of the females were victims of domestic violence. Non-Norwegians, unemployed, and people living in economically deprived areas of the community were over represented. A minority of the assault victims wanted to press legal charges. From the postal survey (n=1264, response rate 43%) few unrecognized victims of violence could be identified among our patients. CONCLUSIONS: An accident and emergency department registration of violence victims will mostly identify male victims of street violence.
@article{steen_violence_2004,
title = {Violence in an urban community from the perspective of an accident and emergency department: a two-year prospective study},
volume = {10},
issn = {1234-1010},
shorttitle = {Violence in an urban community from the perspective of an accident and emergency department},
abstract = {BACKGROUND: Information about violence in a given community is usually based on crime statistics. The aim of this study was to explore violence in an urban community from the perspective of an accident and emergency department.
MATERIAL/METHODS: All assault victims treated at the Bergen Accident and Emergency Department (AED) during a two-year period (1994-1996) were prospectively registered, and data were collected about the patients and the assault incidents. To assess the proportion of unrecognized assault victims treated at the AED, an anonymous questionnaire was sent to all adult patients (first-time consultations) who visited the AED during a ten-day period in 1997.
RESULTS: 1803 assault victims were registered, 433 of whom (24\%) were females. Most of the victims were young men assaulted at public locations, under the influence of alcohol, often by unknown attackers, and frequently feeling that the attack was unprovoked (and thus defined as street violence). Few victims of child abuse or elder abuse were identified. About 40\% of the females were victims of domestic violence. Non-Norwegians, unemployed, and people living in economically deprived areas of the community were over represented. A minority of the assault victims wanted to press legal charges. From the postal survey (n=1264, response rate 43\%) few unrecognized victims of violence could be identified among our patients.
CONCLUSIONS: An accident and emergency department registration of violence victims will mostly identify male victims of street violence.},
language = {eng},
number = {2},
journal = {Medical Science Monitor: International Medical Journal of Experimental and Clinical Research},
author = {Steen, Knut and Hunskaar, Steinar},
month = feb,
year = {2004},
pmid = {14737047},
keywords = {Adolescent, Adult, Child, Child, Preschool, Crime Victims, Domestic Violence, Emergency Service, Hospital, Female, Humans, Infant, Infant, Newborn, Male, Middle Aged, Periodicity, Prospective Studies, Surveys and Questionnaires, Time Factors, Urban Population, Violence},
pages = {CR75--79},
}Deletion of vanilloid receptor 1-expressing primary afferent neurons for pain control. Karai, L., Brown, D. C., Mannes, A. J., Connelly, S. T., Brown, J., Gandal, M., Wellisch, O. M., Neubert, J. K., Olah, Z., & Iadarola, M. J. The Journal of Clinical Investigation, 113(9):1344–1352, May, 2004. 00000
doi abstract bibtex
doi abstract bibtex
Control of cancer, neuropathic, and postoperative pain is frequently inadequate or compromised by debilitating side effects. Inhibition or removal of certain nociceptive neurons, while retaining all other sensory modalities and motor function, would represent a new therapeutic approach to control severe pain. The enriched expression of transient receptor potential cation channel, subfamily V, member 1 (TRPV1; also known as the vanilloid receptor, VR1) in nociceptive neurons of the dorsal root and trigeminal ganglia allowed us to test this concept. Administration of the potent TRPV1 agonist resiniferatoxin (RTX) to neuronal perikarya induces calcium cytotoxicity by opening the TRPV1 ion channel and selectively ablates nociceptive neurons. This treatment blocks experimental inflammatory hyperalgesia and neurogenic inflammation in rats and naturally occurring cancer and debilitating arthritic pain in dogs. Sensations of touch, proprioception, and high-threshold mechanosensitive nociception, as well as locomotor function, remained intact in both species. In separate experiments directed at postoperative pain control, subcutaneous administration of RTX transiently disrupted nociceptive nerve endings, yielding reversible analgesia. In human dorsal root ganglion cultures, RTX induced a prolonged increase in intracellular calcium in vanilloid-sensitive neurons, while leaving other, adjacent neurons unaffected. The results suggest that nociceptive neuronal or nerve terminal deletion will be effective and broadly applicable as strategies for pain management.
@article{karai_deletion_2004,
title = {Deletion of vanilloid receptor 1-expressing primary afferent neurons for pain control},
volume = {113},
issn = {0021-9738},
doi = {10.1172/JCI20449},
abstract = {Control of cancer, neuropathic, and postoperative pain is frequently inadequate or compromised by debilitating side effects. Inhibition or removal of certain nociceptive neurons, while retaining all other sensory modalities and motor function, would represent a new therapeutic approach to control severe pain. The enriched expression of transient receptor potential cation channel, subfamily V, member 1 (TRPV1; also known as the vanilloid receptor, VR1) in nociceptive neurons of the dorsal root and trigeminal ganglia allowed us to test this concept. Administration of the potent TRPV1 agonist resiniferatoxin (RTX) to neuronal perikarya induces calcium cytotoxicity by opening the TRPV1 ion channel and selectively ablates nociceptive neurons. This treatment blocks experimental inflammatory hyperalgesia and neurogenic inflammation in rats and naturally occurring cancer and debilitating arthritic pain in dogs. Sensations of touch, proprioception, and high-threshold mechanosensitive nociception, as well as locomotor function, remained intact in both species. In separate experiments directed at postoperative pain control, subcutaneous administration of RTX transiently disrupted nociceptive nerve endings, yielding reversible analgesia. In human dorsal root ganglion cultures, RTX induced a prolonged increase in intracellular calcium in vanilloid-sensitive neurons, while leaving other, adjacent neurons unaffected. The results suggest that nociceptive neuronal or nerve terminal deletion will be effective and broadly applicable as strategies for pain management.},
language = {eng},
number = {9},
journal = {The Journal of Clinical Investigation},
author = {Karai, Laszlo and Brown, Dorothy C. and Mannes, Andrew J. and Connelly, Stephen T. and Brown, Jacob and Gandal, Michael and Wellisch, Ofer M. and Neubert, John K. and Olah, Zoltan and Iadarola, Michael J.},
month = may,
year = {2004},
pmid = {15124026},
pmcid = {PMC398431},
note = {00000 },
keywords = {Adult, Analgesia, Animals, Calcium, Cells, Cultured, Diterpenes, Dogs, Dose-Response Relationship, Drug, Extravasation of Diagnostic and Therapeutic Materials, Ganglia, Spinal, Humans, Male, Microinjections, Neurons, Afferent, Nociceptors, Pain Management, Pain Measurement, Rats, Rats, Sprague-Dawley, Receptors, Drug, Stereotaxic Techniques, Time Factors, Trigeminal Ganglion},
pages = {1344--1352}
}Visual attention: Bottom-up versus top-down. Connor, C. E, Egeth, H. E, & Yantis, S. Curr Biol, 14(19):R850-2, 2004.
doi abstract bibtex
doi abstract bibtex
Visual attention is attracted by salient stimuli that 'pop out' from their surroundings. Attention can also be voluntarily directed to objects of current importance to the observer. What happens in the brain when these two processes interact?
@Article{Connor2004,
author = {Charles E Connor and Howard E Egeth and Steven Yantis},
journal = {Curr Biol},
title = {Visual attention: {B}ottom-up versus top-down.},
year = {2004},
number = {19},
pages = {R850-2},
volume = {14},
abstract = {Visual attention is attracted by salient stimuli that 'pop out' from
their surroundings. Attention can also be voluntarily directed to
objects of current importance to the observer. What happens in the
brain when these two processes interact?},
doi = {10.1016/j.cub.2004.09.041},
keywords = {Attention, Color Perception, Humans, Models, Pattern Recognition, Psychological, Time Factors, Visual, Visual Fields, Visual Pathways, Visual Perception, 15458666},
}Effects of the brominated flame retardants hexabromocyclododecane (HBCDD), and tetrabromobisphenol A (TBBPA), on hepatic enzymes and other biomarkers in juvenile rainbow trout and feral eelpout. Ronisz, D, Finne, E F., Karlsson, H, & Förlin, L Aquatic toxicology, 69(3):229–45, August, 2004.
Paper doi abstract bibtex
Paper doi abstract bibtex Brominated flame retardants (BFRs) leak out in the environment, including the aquatic one. Despite this, sublethal effects of these chemicals are poorly investigated in fish. In this study, a screening of selected biomarkers in juvenile rainbow trout (Oncorhynchus mykiss) and feral eelpout (Zoarces viviparus) was performed after exposure to hexabromocyclododecane (HBCDD) and tetrabromobisphenol A (TBBPA). Rainbow trout was injected intraperitoneally (i.p.) with HBCDD or TBBPA. Two out of four short-term experiments with HBCDD showed an increase in the activity of catalase. A 40% increase in liver somatic index (LSI) could be observed after 28 days. HBCDD did also seem to have an inhibitory effect on CYP1A's activity (ethoxyresorufin-O-deethylase (EROD)). A putative peroxisome proliferating activity of the compound was investigated without giving a definite answer. HBCDD did not seem to be estrogenic or genotoxic. TBBPA increased the activity of glutathione reductase (GR) after 4, 14 and 28 days in rainbow trout suggesting a possible role of this compound in inducing oxidative stress. The compound did not seem to be estrogenic. TBBPA seemed to compete with the artificial substrate ethoxyresorufin in vitro, during the EROD assay. In eelpout, only one 5 days in vivo experiment was performed. Neither of the compounds gave rise to any effect in this fish. This was the first screening of sublethal effects of the two chemicals in fish, using high doses. Our results indicate that there is a need for further studies of long-term, low-dose effects of these two widely used flame retardants.
@article{ronisz_effects_2004,
title = {Effects of the brominated flame retardants hexabromocyclododecane ({HBCDD}), and tetrabromobisphenol {A} ({TBBPA}), on hepatic enzymes and other biomarkers in juvenile rainbow trout and feral eelpout.},
volume = {69},
issn = {0166-445X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15276329},
doi = {10.1016/j.aquatox.2004.05.007},
abstract = {Brominated flame retardants (BFRs) leak out in the environment, including the aquatic one. Despite this, sublethal effects of these chemicals are poorly investigated in fish. In this study, a screening of selected biomarkers in juvenile rainbow trout (Oncorhynchus mykiss) and feral eelpout (Zoarces viviparus) was performed after exposure to hexabromocyclododecane (HBCDD) and tetrabromobisphenol A (TBBPA). Rainbow trout was injected intraperitoneally (i.p.) with HBCDD or TBBPA. Two out of four short-term experiments with HBCDD showed an increase in the activity of catalase. A 40\% increase in liver somatic index (LSI) could be observed after 28 days. HBCDD did also seem to have an inhibitory effect on CYP1A's activity (ethoxyresorufin-O-deethylase (EROD)). A putative peroxisome proliferating activity of the compound was investigated without giving a definite answer. HBCDD did not seem to be estrogenic or genotoxic. TBBPA increased the activity of glutathione reductase (GR) after 4, 14 and 28 days in rainbow trout suggesting a possible role of this compound in inducing oxidative stress. The compound did not seem to be estrogenic. TBBPA seemed to compete with the artificial substrate ethoxyresorufin in vitro, during the EROD assay. In eelpout, only one 5 days in vivo experiment was performed. Neither of the compounds gave rise to any effect in this fish. This was the first screening of sublethal effects of the two chemicals in fish, using high doses. Our results indicate that there is a need for further studies of long-term, low-dose effects of these two widely used flame retardants.},
number = {3},
journal = {Aquatic toxicology},
author = {Ronisz, D and Finne, E Farmen and Karlsson, H and Förlin, L},
month = aug,
year = {2004},
pmid = {15276329},
keywords = {Animals, Blotting, Brominated, Brominated: chemistry, Brominated: toxicity, Catalase, Catalase: metabolism, Cytochrome P-450 CYP1A1, Cytochrome P-450 CYP1A1: metabolism, Cytosol, Cytosol: enzymology, Enzyme-Linked Immunosorbent Assay, Flame Retardants: toxicity, Flame retardants, Gas Chromatography-Mass Spectrometry, Glutathione Reductase, Glutathione Reductase: metabolism, Hydrocarbons, Liver, Liver: drug effects, Liver: enzymology, Microsomes, Oncorhynchus mykiss, Oncorhynchus mykiss: metabolism, Organ Size, Perciformes, Perciformes: metabolism, Polybrominated Biphenyls, Polybrominated Biphenyls: chemistry, Polybrominated Biphenyls: toxicity, Spectrophotometry, Time Factors, Ultraviolet, Western, frbldg, frelec, tox},
pages = {229--45},
}Telomerase inhibition and cell growth arrest after telomestatin treatment in multiple myeloma. Shammas, M. a, Reis, R. J S., Li, C., Koley, H., Hurley, L. H, Anderson, K. C, & Munshi, N. C Clinical cancer research : an official journal of the American Association for Cancer Research, 10(2):770–6, January, 2004.
Paper abstract bibtex
Paper abstract bibtex The aim of this study was to test the efficacy of telomestatin, an intramolecular G-quadruplex intercalating drug with specificity for telomeric sequences, as a potential therapeutic agent for multiple myeloma.
@article{Shammas2004,
title = {Telomerase inhibition and cell growth arrest after telomestatin treatment in multiple myeloma.},
volume = {10},
issn = {1078-0432},
url = {http://www.ncbi.nlm.nih.gov/pubmed/14760100},
abstract = {The aim of this study was to test the efficacy of telomestatin, an intramolecular G-quadruplex intercalating drug with specificity for telomeric sequences, as a potential therapeutic agent for multiple myeloma.},
number = {2},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
author = {Shammas, Masood a and Reis, Robert J Shmookler and Li, Cheng and Koley, Hemanta and Hurley, Laurence H and Anderson, Kenneth C and Munshi, Nikhil C},
month = jan,
year = {2004},
pmid = {14760100},
keywords = {\#nosource, Apoptosis, Cell Cycle, Cell Division, Cell Line, Cell Survival, DNA Repair, Dose-Response Relationship, Drug, Gene Expression Regulation, Genetic, Humans, Multiple Myeloma, Multiple Myeloma: drug therapy, Multiple Myeloma: enzymology, Multiple Myeloma: pathology, Neoplastic, Oligonucleotide Array Sequence Analysis, Oxazoles, Oxazoles: pharmacology, Recombination, Telomerase, Telomerase: antagonists \& inhibitors, Telomerase: metabolism, Telomere, Telomere: metabolism, Time Factors, Tumor},
pages = {770--6},
}Neanderthals and the modern human colonization of Europe. Mellars, P. Nature, 432(7016):461-5, 2004.
doi abstract bibtex
doi abstract bibtex
The fate of the Neanderthal populations of Europe and western Asia has gripped the popular and scientific imaginations for the past century. Following at least 200,000 years of successful adaptation to the glacial climates of northwestern Eurasia, they disappeared abruptly between 30,000 and 40,000 years ago, to be replaced by populations all but identical to modern humans. Recent research suggests that the roots of this dramatic population replacement can be traced far back to events on another continent, with the appearance of distinctively modern human remains and artefacts in eastern and southern Africa.
@Article{Mellars2004,
author = {Paul Mellars},
journal = {Nature},
title = {Neanderthals and the modern human colonization of {E}urope.},
year = {2004},
number = {7016},
pages = {461-5},
volume = {432},
abstract = {The fate of the Neanderthal populations of Europe and western Asia
has gripped the popular and scientific imaginations for the past
century. Following at least 200,000 years of successful adaptation
to the glacial climates of northwestern Eurasia, they disappeared
abruptly between 30,000 and 40,000 years ago, to be replaced by populations
all but identical to modern humans. Recent research suggests that
the roots of this dramatic population replacement can be traced far
back to events on another continent, with the appearance of distinctively
modern human remains and artefacts in eastern and southern Africa.},
doi = {10.1038/nature03103},
keywords = {Animals, Attention, Brain, Decision Making, Face, Female, Haplorhini, Housing, Humans, Magnetic Resonance Imaging, Male, Models, Neurological, Pattern Recognition, Visual, Photic Stimulation, Prefrontal Cortex, Research Support, Non-U.S. Gov't, U.S. Gov't, P.H.S., Visual Perception, Choice Behavior, Cognition, Dopamine, Learning, Schizophrenia, Substance-Related Disorders, Generalization (Psychology), Motor Skills, Non-P.H.S., Nerve Net, Neuronal Plasticity, Perception, Cerebral Cortex, Memory, Neurons, Sound Localization, Synapses, Synaptic Transmission, Neural Pathways, Non-, Acoustic Stimulation, Adult, Age of Onset, Aging, Blindness, Child, Preschool, Infant, Newborn, Pitch Perception, Analysis of Variance, Animal Welfare, Laboratory, Behavior, Animal, Hybridization, Genetic, Maze Learning, Mice, Inbred C57BL, Inbred DBA, Phenotype, Reproducibility of Results, Darkness, Deafness, Finches, Sleep, Sound, Sunlight, Time Factors, Vocalization, Energy Metabolism, Evolution, Fossils, History, Ancient, Hominidae, Biological, Physical Endurance, Running, Skeleton, Walking, Acoustics, Auditory Perception, Cues, Discrimination Learning, Pair Bond, Social Behavior, Songbirds, Adolescent, England, Habituation (Psychophysiology), Korea, Language, Semantics, Vocabulary, Action Potentials, Hippocampus, Pyramidal Cells, Rats, Rotation, Australia, Brachyura, Cooperative Behavior, Logistic Models, Territoriality, Africa, Archaeology, Emigration and Immigration, Europe, Geography, Phylogeny, Population Dynamics, 15565144},
}2003 (2)
Stability of intramolecular DNA quadruplexes: comparison with DNA duplexes. Risitano, A. & Fox, K. R Biochemistry, 42(21):6507–13, July, 2003.
Paper doi abstract bibtex
Paper doi abstract bibtex We have determined the stability of intramolecular quadruplexes that are formed by a variety of G-rich sequences, using oligonucleotides containing appropriately placed fluorophores and quenchers. The stability of these quadruplexes is compared with that of the DNA duplexes that are formed on addition of complementary C-rich oligonucleotides. We find that the linkers joining the G-tracts are not essential for folding and can be replaced with nonnucleosidic moieties, though their sequence composition profoundly affects quadruplex stability. Although the human telomere repeat sequence d[G(3)(TTAG(3))(3)] folds into a quadruplex structure, this forms a duplex in the presence of the complementary C-rich strand at physiological conditions. The Tetrahymena sequence d[G(4)(T(2)G(4))(3)], the sequence d[G(3)(T(2)G(3))(3)], and sequences related to regions of the c-myc promoter d(G(4)AG(4)T)(2) and d(G(4)AG(3)T)(2) preferentially adopt the quadruplex form in potassium-containing buffers, even in the presence of a 50-fold excess of their complementary C-rich strands, though the duplex predominates in the presence of sodium. The HIV integrase inhibitor d[G(3)(TG(3))(3)] forms an extremely stable quadruplex which is not affected by addition of a 50-fold excess of the complementary C-rich strand in both potassium- and sodium-containing buffers. Replacing the TTA loops of the human telomeric repeat with AAA causes a large decrease in quadruplex stability, though a sequence with AAA in the first loop and TTT in the second and third loops is slightly more stable.
@article{Risitano2003,
title = {Stability of intramolecular {DNA} quadruplexes: comparison with {DNA} duplexes.},
volume = {42},
issn = {0006-2960},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12767234},
doi = {10.1021/bi026997v},
abstract = {We have determined the stability of intramolecular quadruplexes that are formed by a variety of G-rich sequences, using oligonucleotides containing appropriately placed fluorophores and quenchers. The stability of these quadruplexes is compared with that of the DNA duplexes that are formed on addition of complementary C-rich oligonucleotides. We find that the linkers joining the G-tracts are not essential for folding and can be replaced with nonnucleosidic moieties, though their sequence composition profoundly affects quadruplex stability. Although the human telomere repeat sequence d[G(3)(TTAG(3))(3)] folds into a quadruplex structure, this forms a duplex in the presence of the complementary C-rich strand at physiological conditions. The Tetrahymena sequence d[G(4)(T(2)G(4))(3)], the sequence d[G(3)(T(2)G(3))(3)], and sequences related to regions of the c-myc promoter d(G(4)AG(4)T)(2) and d(G(4)AG(3)T)(2) preferentially adopt the quadruplex form in potassium-containing buffers, even in the presence of a 50-fold excess of their complementary C-rich strands, though the duplex predominates in the presence of sodium. The HIV integrase inhibitor d[G(3)(TG(3))(3)] forms an extremely stable quadruplex which is not affected by addition of a 50-fold excess of the complementary C-rich strand in both potassium- and sodium-containing buffers. Replacing the TTA loops of the human telomeric repeat with AAA causes a large decrease in quadruplex stability, though a sequence with AAA in the first loop and TTT in the second and third loops is slightly more stable.},
number = {21},
journal = {Biochemistry},
author = {Risitano, Antonina and Fox, Keith R},
month = jul,
year = {2003},
pmid = {12767234},
keywords = {\#nosource, Animals, DNA, DNA: chemistry, Fluorescence, Genetic, HIV Integrase Inhibitors, HIV Integrase Inhibitors: chemistry, Humans, Nucleic Acid Conformation, Oligonucleotides, Oligonucleotides: chemistry, Promoter Regions, Protein Conformation, Protein Denaturation, Spectrometry, Telomere, Telomere: chemistry, Temperature, Tetrahymena, Tetrahymena: metabolism, Thermodynamics, Time Factors},
pages = {6507--13},
}Late-onset cytomegalovirus reactivation in critically ill renal transplant patients. Jochimsen, F., Westhoff, T., Engelmann, E., Schafer, J., Offermann, G., & Zidek, W. Transplantation, 76(2):430--432, July, 2003.
doi abstract bibtex
doi abstract bibtex
BACKGROUND: Cytomegalovirus (CMV) reactivation occurs frequently in the first months after renal transplantation. However, reports concerning long-term kidney transplant recipients are rare and have always pertained to symptomatic CMV disease. METHODS: We report four cases of late-onset asymptomatic CMV reactivation in critically ill renal transplant patients who suffered from severe bacterial infections and in whom CMV antigenemia was observed. RESULTS AND CONCLUSION: CMV reactivation in these patients might indicate an additional disturbance in the patients' immune defenses at the time of critical illness, possibly even necessitating a temporary reduction in immunosuppressive therapy. Prospective, controlled trials are needed to define the role of CMV antigenemia in critically ill patients, including the role of antiviral therapy for asymptomatic reactivations.
@article{jochimsen_late-onset_2003,
title = {Late-onset cytomegalovirus reactivation in critically ill renal transplant patients.},
volume = {76},
issn = {0041-1337 0041-1337},
doi = {10.1097/01.TP.0000075091.80548.5B},
abstract = {BACKGROUND: Cytomegalovirus (CMV) reactivation occurs frequently in the first months after renal transplantation. However, reports concerning long-term kidney transplant recipients are rare and have always pertained to symptomatic CMV disease. METHODS: We report four cases of late-onset asymptomatic CMV reactivation in critically ill renal transplant patients who suffered from severe bacterial infections and in whom CMV antigenemia was observed. RESULTS AND CONCLUSION: CMV reactivation in these patients might indicate an additional disturbance in the patients' immune defenses at the time of critical illness, possibly even necessitating a temporary reduction in immunosuppressive therapy. Prospective, controlled trials are needed to define the role of CMV antigenemia in critically ill patients, including the role of antiviral therapy for asymptomatic reactivations.},
language = {eng},
number = {2},
journal = {Transplantation},
author = {Jochimsen, Friederike and Westhoff, Timm and Engelmann, Elisabeth and Schafer, Jurgen-Heiner and Offermann, Gerd and Zidek, Walter},
month = jul,
year = {2003},
pmid = {12883206},
keywords = {*Kidney Transplantation, Acute Disease, Aged, Antiviral Agents/administration \& dosage, Bacterial Infections/*complications, Critical Illness, Cytomegalovirus Infections/*complications/drug therapy, Female, Ganciclovir/administration \& dosage, Humans, Middle Aged, Neutrophils/virology, Phosphoproteins/analysis, Recurrence, Superinfection/complications, Time Factors, Viral Matrix Proteins/analysis},
pages = {430--432}
}2002 (6)
Hospital-acquired pneumonia: microbiological data and potential adequacy of antimicrobial regimens. Leroy O, Giradie P, Yazdanpanah Y, Georges H, Alfandari S, Sanders V, Devos P, & Beaucaire G Eur. Resp. J., 20:432-439, 2002.
Paper doi bibtex
Paper doi bibtex @article{leroy_o_HOSPITALACQUIRED_2002,
title = {Hospital-acquired pneumonia: microbiological data and potential adequacy of antimicrobial regimens},
volume = {20},
issn = {0903-1936},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12212978},
DOI = {10.1183/09031936.02.00267602},
Language = {English},
Journal = {Eur. Resp. J.},
author = {{Leroy O} and {Giradie P} and {Yazdanpanah Y} and {Georges H} and {Alfandari S} and {Sanders V} and {Devos P} and {Beaucaire G}},
year = {2002},
keywords = {Aged, Anti-Bacterial Agents/therapeutic use*, Cross Infection/drug therapy*, Cross Infection/etiology, Cross Infection/microbiology*, Female, Gram-Negative Bacteria/drug effects*, Gram-Negative Bacteria/isolation & purification*, Humans, Male, Middle Aged, Outcome Assessment, Health Care, Pneumonia/drug therapy*, Pneumonia/etiology, Pneumonia/microbiology*, Retrospective Studies, Risk Factors, Severity of Illness Index, Time Factors},
pages = {432-439}
}Hospital-acquired pneumonia: microbiological data and potential adequacy of antimicrobial regimens. Leroy, O., Giradie, P., Yazdanpanah, Y., Georges, H., Alfandari, S., Sanders, V., Devos, P., & Beaucaire, G. The European respiratory journal, 20(2):432–439, August, 2002.
abstract bibtex
abstract bibtex
Adequate antimicrobial therapy is a main approach employed to decrease the mortality associated with hospital-acquired pneumonia (HAP). All methods that optimise empirical treatment without increasing antibiotic selective pressure are relevant. Categorisation of patients according to HAP time of onset, severity and risk factors (American Thoracic Society (ATS) classification) or duration of mechanical ventilation and prior antibiotics (Trouillet's classification) are two such methods. The aim of this study was to catagorise patients with HAP according to these classifications and to determine the frequency of resistant pathogens and the most adequate antimicrobial regimens in each group. A total 124 patients with bacteriologically proven HAP were studied. The ATS classification categorised patients by increasing frequency of resistant pathogens from 0-30.3%. The ATS empirical antibiotic recommendations appeared valid but proposed combinations including vancomycin for 72.5% of patients. Trouillet's classification categorised patients into four groups with a frequency of resistant pathogens from 4.9-35.6%. Vancomycin was proposed for 48.5% of patients. The American Thoracic Society classification appears to be more specific than Trouillet's for predicting the absence of resistant causative pathogens in hospital-acquired pneumonia but could lead to a greater use of vancomycin. Stratification combining the two classifications is an interesting alternative.
@article{leroy_hospital-acquired_2002,
title = {Hospital-acquired pneumonia: microbiological data and potential adequacy of antimicrobial regimens.},
volume = {20},
issn = {0903-1936 0903-1936},
abstract = {Adequate antimicrobial therapy is a main approach employed to decrease the mortality associated with hospital-acquired pneumonia (HAP). All methods that optimise empirical treatment without increasing antibiotic selective pressure are relevant. Categorisation of patients according to HAP time of onset, severity and risk factors (American Thoracic Society (ATS) classification) or duration of mechanical ventilation and prior antibiotics (Trouillet's classification) are two such methods. The aim of this study was to catagorise patients with HAP according to these classifications and to determine the frequency of resistant pathogens and the most adequate antimicrobial regimens in each group. A total 124 patients with bacteriologically proven HAP were studied. The ATS classification categorised patients by increasing frequency of resistant pathogens from 0-30.3\%. The ATS empirical antibiotic recommendations appeared valid but proposed combinations including vancomycin for 72.5\% of patients. Trouillet's classification categorised patients into four groups with a frequency of resistant pathogens from 4.9-35.6\%. Vancomycin was proposed for 48.5\% of patients. The American Thoracic Society classification appears to be more specific than Trouillet's for predicting the absence of resistant causative pathogens in hospital-acquired pneumonia but could lead to a greater use of vancomycin. Stratification combining the two classifications is an interesting alternative.},
language = {eng},
number = {2},
journal = {The European respiratory journal},
author = {Leroy, O. and Giradie, P. and Yazdanpanah, Y. and Georges, H. and Alfandari, S. and Sanders, V. and Devos, P. and Beaucaire, G.},
month = aug,
year = {2002},
pmid = {12212978},
keywords = {Humans, Anti-Bacterial Agents/*therapeutic use, Female, Aged, Male, Middle Aged, Retrospective Studies, Risk Factors, Severity of Illness Index, Outcome Assessment (Health Care), Time Factors, Cross Infection/*drug therapy/etiology/*microbiology, Gram-Negative Bacteria/*drug effects/*isolation \& purification, Pneumonia/*drug therapy/etiology/*microbiology},
pages = {432--439}
}Responses of primate visual cortical V4 neurons to simultaneously presented stimuli. Gawne, T. J & Martin, J. M J Neurophysiol, 88(3):1128-35, 2002.
abstract bibtex
abstract bibtex
We report here results from 45 primate V4 visual cortical neurons to the preattentive presentations of seven different patterns located in two separate areas of the same receptive field and to combinations of the patterns in the two locations. For many neurons, we could not determine any clear relationship for the responses to two simultaneous stimuli. However, for a substantial fraction of the neurons we found that the firing rate was well modeled as the maximum firing rate of each stimulus presented separately. It has previously been proposed that taking the maximum of the inputs ("MAX" operator) could be a useful operation for neurons in visual cortex, although there has until now been little direct physiological evidence for this hypothesis. Our results here provide direct support for the hypothesis that the MAX operator plays a significant (although certainly not exclusive) role in generating the receptive field properties of visual cortical neurons.
@Article{Gawne2002,
author = {Timothy J Gawne and Julie M Martin},
journal = {J Neurophysiol},
title = {Responses of primate visual cortical {V}4 neurons to simultaneously presented stimuli.},
year = {2002},
number = {3},
pages = {1128-35},
volume = {88},
abstract = {We report here results from 45 primate V4 visual cortical neurons
to the preattentive presentations of seven different patterns located
in two separate areas of the same receptive field and to combinations
of the patterns in the two locations. For many neurons, we could
not determine any clear relationship for the responses to two simultaneous
stimuli. However, for a substantial fraction of the neurons we found
that the firing rate was well modeled as the maximum firing rate
of each stimulus presented separately. It has previously been proposed
that taking the maximum of the inputs ("MAX" operator) could be a
useful operation for neurons in visual cortex, although there has
until now been little direct physiological evidence for this hypothesis.
Our results here provide direct support for the hypothesis that the
MAX operator plays a significant (although certainly not exclusive)
role in generating the receptive field properties of visual cortical
neurons.},
keywords = {Computing Methodologies, Human, Language, Learning, Mental Processes, Models, Theoretical, Stochastic Processes, Support, U.S. Gov't, Non-P.H.S., Cognition, Linguistics, Neural Networks (Computer), Practice (Psychology), Non-U.S. Gov't, Memory, Psychological, Task Performance and Analysis, Time Factors, Visual Perception, Adult, Attention, Discrimination Learning, Female, Male, Short-Term, Mental Recall, Orientation, Pattern Recognition, Visual, Perceptual Masking, Reading, Concept Formation, Form Perception, Animals, Corpus Striatum, Shrews, P.H.S., Visual Cortex, Visual Pathways, Acoustic Stimulation, Auditory Cortex, Auditory Perception, Cochlea, Ear, Gerbillinae, Glycine, Hearing, Neurons, Space Perception, Strychnine, Adolescent, Decision Making, Reaction Time, Astrocytoma, Brain Mapping, Brain Neoplasms, Cerebral Cortex, Electric Stimulation, Electrophysiology, Epilepsy, Temporal Lobe, Evoked Potentials, Frontal Lobe, Noise, Parietal Lobe, Scalp, Child, Language Development, Psycholinguistics, Brain, Perception, Speech, Vocalization, Animal, Discrimination (Psychology), Hippocampus, Rats, Calcium, Chelating Agents, Excitatory Postsynaptic Potentials, Glutamic Acid, Guanosine Diphosphate, In Vitro, Neuronal Plasticity, Pyramidal Cells, Receptors, AMPA, Metabotropic Glutamate, N-Methyl-D-Aspartate, Somatosensory Cortex, Synapses, Synaptic Transmission, Thionucleotides, Action Potentials, Calcium Channels, L-Type, Electric Conductivity, Entorhinal Cortex, Neurological, Long-Evans, Infant, Mathematics, Statistics, Probability Learning, Problem Solving, Psychophysics, Association Learning, Child Psychology, Habituation (Psychophysiology), Probability Theory, Analysis of Variance, Semantics, Symbolism, Behavior, Eye Movements, Macaca mulatta, Prefrontal Cortex, Cats, Dogs, Haplorhini, Photic Stimulation, Electroencephalography, Nervous System Physiology, Darkness, Grasshoppers, Light, Membrane Potentials, Neural Inhibition, Afferent, Picrotoxin, Vision, 12205134},
}Intrinsic and extrinsic contributions to stochasticity in gene expression. Swain, P., S., Elowitz, M., B., & Siggia, E., D. Proceedings of the National Academy of Sciences of the United States of America, 99(20):12795-12800, 2002.
Paper abstract bibtex
Paper abstract bibtex Gene expression is a stochastic, or "noisy," process. This noise comes about in two ways. The inherent stochasticity of biochemical processes such as transcription and translation generates "intrinsic" noise. In addition, fluctuations in the amounts or states of other cellular components lead indirectly to variation in the expression of a particular gene and thus represent "extrinsic" noise. Here, we show how the total variation in the level of expression of a given gene can be decomposed into its intrinsic and extrinsic components. We demonstrate theoretically that simultaneous measurement of two identical genes per cell enables discrimination of these two types of noise. Analytic expressions for intrinsic noise are given for a model that involves all the major steps in transcription and translation. These expressions give the sensitivity to various parameters, quantify the deviation from Poisson statistics, and provide a way of fitting experiment. Transcription dominates the intrinsic noise when the average number of proteins made per mRNA transcript is greater than approximately 2. Below this number, translational effects also become important. Gene replication and cell division, included in the model, cause protein numbers to tend to a limit cycle. We calculate a general form for the extrinsic noise and illustrate it with the particular case of a single fluctuating extrinsic variable-a repressor protein, which acts on the gene of interest. All results are confirmed by stochastic simulation using plausible parameters for Escherichia coli.
@article{
title = {Intrinsic and extrinsic contributions to stochasticity in gene expression.},
type = {article},
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keywords = {Biophysical Phenomena,Biophysics,Escherichia coli,Escherichia coli: metabolism,Gene Expression Regulation,Genetic,Messenger,Messenger: metabolism,Models,Protein Biosynthesis,RNA,Theoretical,Time Factors,Transcription},
pages = {12795-12800},
volume = {99},
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last_modified = {2015-08-20T10:42:27.000Z},
read = {false},
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confirmed = {true},
hidden = {false},
citation_key = {Swain2002},
abstract = {Gene expression is a stochastic, or "noisy," process. This noise comes about in two ways. The inherent stochasticity of biochemical processes such as transcription and translation generates "intrinsic" noise. In addition, fluctuations in the amounts or states of other cellular components lead indirectly to variation in the expression of a particular gene and thus represent "extrinsic" noise. Here, we show how the total variation in the level of expression of a given gene can be decomposed into its intrinsic and extrinsic components. We demonstrate theoretically that simultaneous measurement of two identical genes per cell enables discrimination of these two types of noise. Analytic expressions for intrinsic noise are given for a model that involves all the major steps in transcription and translation. These expressions give the sensitivity to various parameters, quantify the deviation from Poisson statistics, and provide a way of fitting experiment. Transcription dominates the intrinsic noise when the average number of proteins made per mRNA transcript is greater than approximately 2. Below this number, translational effects also become important. Gene replication and cell division, included in the model, cause protein numbers to tend to a limit cycle. We calculate a general form for the extrinsic noise and illustrate it with the particular case of a single fluctuating extrinsic variable-a repressor protein, which acts on the gene of interest. All results are confirmed by stochastic simulation using plausible parameters for Escherichia coli.},
bibtype = {article},
author = {Swain, Peter S and Elowitz, Michael B and Siggia, Eric D},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {20}
}The past and future of the past tense. Pinker, S. & Ullman, M. T Trends Cogn Sci, 6(11):456-463, 2002.
abstract bibtex
abstract bibtex
What is the interaction between storage and computation in language processing? What is the psychological status of grammatical rules? What are the relative strengths of connectionist and symbolic models of cognition? How are the components of language implemented in the brain? The English past tense has served as an arena for debates on these issues. We defend the theory that irregular past-tense forms are stored in the lexicon, a division of declarative memory, whereas regular forms can be computed by a concatenation rule, which requires the procedural system. Irregulars have the psychological, linguistic and neuropsychological signatures of lexical memory, whereas regulars often have the signatures of grammatical processing. Furthermore, because regular inflection is rule-driven, speakers can apply it whenever memory fails.
@Article{Pinker2002a,
author = {Steven Pinker and Michael T Ullman},
journal = {Trends Cogn Sci},
title = {The past and future of the past tense.},
year = {2002},
number = {11},
pages = {456-463},
volume = {6},
abstract = {What is the interaction between storage and computation in language
processing? What is the psychological status of grammatical rules?
What are the relative strengths of connectionist and symbolic models
of cognition? How are the components of language implemented in the
brain? The English past tense has served as an arena for debates
on these issues. We defend the theory that irregular past-tense forms
are stored in the lexicon, a division of declarative memory, whereas
regular forms can be computed by a concatenation rule, which requires
the procedural system. Irregulars have the psychological, linguistic
and neuropsychological signatures of lexical memory, whereas regulars
often have the signatures of grammatical processing. Furthermore,
because regular inflection is rule-driven, speakers can apply it
whenever memory fails.},
keywords = {Computing Methodologies, Human, Language, Learning, Mental Processes, Models, Theoretical, Stochastic Processes, Support, U.S. Gov't, Non-P.H.S., Cognition, Linguistics, Neural Networks (Computer), Practice (Psychology), Non-U.S. Gov't, Memory, Psychological, Task Performance and Analysis, Time Factors, Visual Perception, Adult, Attention, Discrimination Learning, Female, Male, Short-Term, Mental Recall, Orientation, Pattern Recognition, Visual, Perceptual Masking, Reading, Concept Formation, Form Perception, Animals, Corpus Striatum, Shrews, P.H.S., Visual Cortex, Visual Pathways, Acoustic Stimulation, Auditory Cortex, Auditory Perception, Cochlea, Ear, Gerbillinae, Glycine, Hearing, Neurons, Space Perception, Strychnine, Adolescent, Decision Making, Reaction Time, Astrocytoma, Brain Mapping, Brain Neoplasms, Cerebral Cortex, Electric Stimulation, Electrophysiology, Epilepsy, Temporal Lobe, Evoked Potentials, Frontal Lobe, Noise, Parietal Lobe, Scalp, Child, Language Development, Psycholinguistics, Brain, Perception, Speech, Vocalization, Animal, Discrimination (Psychology), Hippocampus, Rats, Calcium, Chelating Agents, Excitatory Postsynaptic Potentials, Glutamic Acid, Guanosine Diphosphate, In Vitro, Neuronal Plasticity, Pyramidal Cells, Receptors, AMPA, Metabotropic Glutamate, N-Methyl-D-Aspartate, Somatosensory Cortex, Synapses, Synaptic Transmission, Thionucleotides, Action Potentials, Calcium Channels, L-Type, Electric Conductivity, Entorhinal Cortex, Neurological, Long-Evans, Infant, Mathematics, Statistics, Probability Learning, Problem Solving, Psychophysics, Association Learning, Child Psychology, Habituation (Psychophysiology), Probability Theory, Analysis of Variance, Semantics, Symbolism, Behavior, Eye Movements, Macaca mulatta, Prefrontal Cortex, Cats, Dogs, Haplorhini, Photic Stimulation, Electroencephalography, Nervous System Physiology, Darkness, Grasshoppers, Light, Membrane Potentials, Neural Inhibition, Afferent, Picrotoxin, Vision, Deoxyglucose, Injections, Microspheres, Neural Pathways, Rhodamines, Choice Behavior, Speech Perception, Verbal Learning, Dominance, Cerebral, Fixation, Ocular, Language Tests, Random Allocation, Comparative Study, Saguinus, Sound Spectrography, Species Specificity, Audiometry, Auditory Threshold, Calibration, Data Interpretation, Statistical, Anesthesia, General, Electrodes, Implanted, Pitch Perception, Sound Localization, Paired-Associate Learning, Serial Learning, Auditory, Age Factors, Motion Perception, Brain Injuries, Computer Simulation, Blindness, Psychomotor Performance, Color Perception, Signal Detection (Psychology), Judgment, ROC Curve, Regression Analysis, Music, Probability, Arm, Cerebrovascular Disorders, Hemiplegia, Movement, Muscle, Skeletal, Myoclonus, Robotics, Magnetoencephalography, Phonetics, Software, Speech Production Measurement, Epilepsies, Partial, Laterality, Stereotaxic Techniques, Germany, Speech Acoustics, Verbal Behavior, Child Development, Instinct, Brain Stem, Coma, Diagnosis, Differential, Hearing Disorders, Hearing Loss, Central, Neuroma, Acoustic, Dendrites, Down-Regulation, Patch-Clamp Techniques, Wistar, Up-Regulation, Aged, Aphasia, Middle Aged, Cones (Retina), Primates, Retina, Retinal Ganglion Cells, Tympanic Membrane, Cell Communication, Extremities, Biological, Motor Activity, Rana catesbeiana, Spinal Cord, Central Nervous System, Motion, Motor Cortex, Intelligence, Macaca fascicularis, Adoption, Critical Period (Psychology), France, Korea, Magnetic Resonance Imaging, Multilingualism, Auditory Pathways, Cochlear Nerve, Loudness Perception, Neural Conduction, Sensory Thresholds, Sound, Language Disorders, 12457895},
}Visual categorization and the primate prefrontal cortex: Neurophysiology and behavior. Freedman, D. J, Riesenhuber, M., Poggio, T., & Miller, E. K J Neurophysiol, 88(2):929-41, 2002.
abstract bibtex
abstract bibtex
The ability to group stimuli into meaningful categories is a fundamental cognitive process. To explore its neuronal basis, we trained monkeys to categorize computer-generated stimuli as "cats" and "dogs." A morphing system was used to systematically vary stimulus shape and precisely define a category boundary. Psychophysical testing and analysis of eye movements suggest that the monkeys categorized the stimuli by attending to multiple stimulus features. Neuronal activity in the lateral prefrontal cortex reflected the category of visual stimuli and changed with learning when a monkey was retrained with the same stimuli assigned to new categories. Further, many neurons showed activity that appeared to reflect the monkey's decision about whether two stimuli were from the same category or not. These results suggest that the lateral prefrontal cortex is an important part of the neuronal circuitry underlying category learning and category-based behaviors.
@Article{Freedman2002,
author = {David J Freedman and Maximilian Riesenhuber and Tomaso Poggio and Earl K Miller},
journal = {J Neurophysiol},
title = {Visual categorization and the primate prefrontal cortex: {N}europhysiology and behavior.},
year = {2002},
number = {2},
pages = {929-41},
volume = {88},
abstract = {The ability to group stimuli into meaningful categories is a fundamental
cognitive process. To explore its neuronal basis, we trained monkeys
to categorize computer-generated stimuli as "cats" and "dogs." A
morphing system was used to systematically vary stimulus shape and
precisely define a category boundary. Psychophysical testing and
analysis of eye movements suggest that the monkeys categorized the
stimuli by attending to multiple stimulus features. Neuronal activity
in the lateral prefrontal cortex reflected the category of visual
stimuli and changed with learning when a monkey was retrained with
the same stimuli assigned to new categories. Further, many neurons
showed activity that appeared to reflect the monkey's decision about
whether two stimuli were from the same category or not. These results
suggest that the lateral prefrontal cortex is an important part of
the neuronal circuitry underlying category learning and category-based
behaviors.},
keywords = {Computing Methodologies, Human, Language, Learning, Mental Processes, Models, Theoretical, Stochastic Processes, Support, U.S. Gov't, Non-P.H.S., Cognition, Linguistics, Neural Networks (Computer), Practice (Psychology), Non-U.S. Gov't, Memory, Psychological, Task Performance and Analysis, Time Factors, Visual Perception, Adult, Attention, Discrimination Learning, Female, Male, Short-Term, Mental Recall, Orientation, Pattern Recognition, Visual, Perceptual Masking, Reading, Concept Formation, Form Perception, Animals, Corpus Striatum, Shrews, P.H.S., Visual Cortex, Visual Pathways, Acoustic Stimulation, Auditory Cortex, Auditory Perception, Cochlea, Ear, Gerbillinae, Glycine, Hearing, Neurons, Space Perception, Strychnine, Adolescent, Decision Making, Reaction Time, Astrocytoma, Brain Mapping, Brain Neoplasms, Cerebral Cortex, Electric Stimulation, Electrophysiology, Epilepsy, Temporal Lobe, Evoked Potentials, Frontal Lobe, Noise, Parietal Lobe, Scalp, Child, Language Development, Psycholinguistics, Brain, Perception, Speech, Vocalization, Animal, Discrimination (Psychology), Hippocampus, Rats, Calcium, Chelating Agents, Excitatory Postsynaptic Potentials, Glutamic Acid, Guanosine Diphosphate, In Vitro, Neuronal Plasticity, Pyramidal Cells, Receptors, AMPA, Metabotropic Glutamate, N-Methyl-D-Aspartate, Somatosensory Cortex, Synapses, Synaptic Transmission, Thionucleotides, Action Potentials, Calcium Channels, L-Type, Electric Conductivity, Entorhinal Cortex, Neurological, Long-Evans, Infant, Mathematics, Statistics, Probability Learning, Problem Solving, Psychophysics, Association Learning, Child Psychology, Habituation (Psychophysiology), Probability Theory, Analysis of Variance, Semantics, Symbolism, Behavior, Eye Movements, Macaca mulatta, Prefrontal Cortex, 12163542},
}2001 (5)
Single molecule detection of double-stranded DNA in poly(methylmethacrylate) and polycarbonate microfluidic devices. Wabuyele, M., B., Ford, S., M., Stryjewski, W., Barrow, J., & Soper, S., a. Electrophoresis, 22(18):3939-48, 10, 2001.
Website abstract bibtex
Website abstract bibtex Single photon burst techniques were used to detect double-stranded DNA molecules in poly(methylmethacrylate) (PM MA) and polycarbonate (PC) microfluidic devices. A confocal epi-illumination detection system was constructed to monitor the fluorescence signature from single DNA molecules that were multiply labeled with the mono-intercalating dye, TOPRO-5, which possessed an absorption maximum at 765 nm allowing excitation with a solid-state diode laser and fluorescence monitoring in the near-infrared (IR). Near-IR excitation minimized autofluorescence produced from the polymer substrate, which was found to be significantly greater when excitation was provided in the visible range (488 nm). A solution containing lambda-DNA (48.5 kbp) was electrokinetically transported through the microfluidic devices at different applied voltages and solution pH values to investigate the effects of polymer substrate on the transport rate and detection efficiency of single molecular events. By applying an autocorrelation analysis to the data, we were able to obtain the molecular transit time of the individual molecules as they passed through the 7 microm laser beam. It was observed that the applied voltage for both devices affected the transport rate. However, solution pH did not alter the transit time for PM MA-based devices since the electroosmotic flow of PMMA was independent of solution pH. In addition, efforts were directed toward optimizing the sampling efficiency (number of molecules passing through the probe volume) by using either hydrodynamically focused flows from a sheath generated by electrokinetic pumping from side channels or reducing the channel width of the microfluidic device. Due to the low electroosmotic flows generated by both PMMA and PC, tight focusing of the sample stream was not possible. However, in PMMA devices, flow gating was observed by applying field strengths > -120 V/cm to the sheath flow channels. By narrowing the microchannel width, the number of molecular events detected per unit time was found to be four times higher in channels with 10 microm widths compared to those of 50 microm, indicating improved sampling efficiency for the narrower channels without significantly deteriorating detection efficiency. Attempts were made to do single molecule sizing of lambda-DNA, M13 (7.2 kbp) and pUC19 (2.7 kbp) using photon burst detection. While the average number of photons for each DNA type were different, the standard deviations were large due to the Gaussian intensity profile of the excitation beam. To demonstrate the sensitivity of single molecule analysis in the near-IR using polymer microfluidic devices, the near-IR chromophore, NN382, wasanalyzed using ourconfocal imager. A detection efficiency of 94% for single NN382 molecules was observed in the PC devices.
@article{
title = {Single molecule detection of double-stranded DNA in poly(methylmethacrylate) and polycarbonate microfluidic devices.},
type = {article},
year = {2001},
identifiers = {[object Object]},
keywords = {Bacteriophage lambda,Bacteriophage lambda: chemistry,DNA, Viral,DNA, Viral: analysis,Electrophoresis, Capillary,Electrophoresis, Capillary: instrumentation,Equipment Design,Fluorescent Dyes,Fluorescent Dyes: analysis,Fluorescent Dyes: chemistry,Fluorometry,Fluorometry: instrumentation,Intercalating Agents,Intercalating Agents: analysis,Intercalating Agents: chemistry,Lasers,Microchemistry,Microchemistry: instrumentation,Molecular Weight,Polycarboxylate Cement,Polycarboxylate Cement: chemistry,Polymethyl Methacrylate,Polymethyl Methacrylate: chemistry,Quinolines,Quinolines: analysis,Quinolines: chemistry,Rheology,Sensitivity and Specificity,Thiazoles,Thiazoles: analysis,Thiazoles: chemistry,Time Factors},
pages = {3939-48},
volume = {22},
websites = {http://www.ncbi.nlm.nih.gov/pubmed/11700724},
month = {10},
id = {a6442936-70ae-3027-b44b-cf57e559a3fe},
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hidden = {false},
citation_key = {Wabuyele2001},
abstract = {Single photon burst techniques were used to detect double-stranded DNA molecules in poly(methylmethacrylate) (PM MA) and polycarbonate (PC) microfluidic devices. A confocal epi-illumination detection system was constructed to monitor the fluorescence signature from single DNA molecules that were multiply labeled with the mono-intercalating dye, TOPRO-5, which possessed an absorption maximum at 765 nm allowing excitation with a solid-state diode laser and fluorescence monitoring in the near-infrared (IR). Near-IR excitation minimized autofluorescence produced from the polymer substrate, which was found to be significantly greater when excitation was provided in the visible range (488 nm). A solution containing lambda-DNA (48.5 kbp) was electrokinetically transported through the microfluidic devices at different applied voltages and solution pH values to investigate the effects of polymer substrate on the transport rate and detection efficiency of single molecular events. By applying an autocorrelation analysis to the data, we were able to obtain the molecular transit time of the individual molecules as they passed through the 7 microm laser beam. It was observed that the applied voltage for both devices affected the transport rate. However, solution pH did not alter the transit time for PM MA-based devices since the electroosmotic flow of PMMA was independent of solution pH. In addition, efforts were directed toward optimizing the sampling efficiency (number of molecules passing through the probe volume) by using either hydrodynamically focused flows from a sheath generated by electrokinetic pumping from side channels or reducing the channel width of the microfluidic device. Due to the low electroosmotic flows generated by both PMMA and PC, tight focusing of the sample stream was not possible. However, in PMMA devices, flow gating was observed by applying field strengths > -120 V/cm to the sheath flow channels. By narrowing the microchannel width, the number of molecular events detected per unit time was found to be four times higher in channels with 10 microm widths compared to those of 50 microm, indicating improved sampling efficiency for the narrower channels without significantly deteriorating detection efficiency. Attempts were made to do single molecule sizing of lambda-DNA, M13 (7.2 kbp) and pUC19 (2.7 kbp) using photon burst detection. While the average number of photons for each DNA type were different, the standard deviations were large due to the Gaussian intensity profile of the excitation beam. To demonstrate the sensitivity of single molecule analysis in the near-IR using polymer microfluidic devices, the near-IR chromophore, NN382, wasanalyzed using ourconfocal imager. A detection efficiency of 94% for single NN382 molecules was observed in the PC devices.},
bibtype = {article},
author = {Wabuyele, M B and Ford, S M and Stryjewski, W and Barrow, J and Soper, S a},
journal = {Electrophoresis},
number = {18}
}Inbreeding in Gredos mountain range (Spain): contribution of multiple consanguinity and intervalley variation. Fuster, V., Jimenez, A., M., & Colantonio, S., E. Hum Biol, 73(2):249-70., 2001.
Paper abstract bibtex
Paper abstract bibtex The present paper examines consanguineous marriages occurring between 1874 and 1975 in three valleys (Tormes, Alberche, and Tietar) in the Sierra de Gredos mountain range, Avila province, Spain. Information was obtained from parish registers of 42 localities, corresponding to a total of 41,696 weddings. Consanguineous marriages were defined as those up to the third degree of consanguinity (second cousins). From 1874 to 1975 the percentage of related mates was 4.45% and the inbreeding coefficient was 0.0011868 (for 1874 to 1917 corresponding figures up to the fourth degree were 16.44% and 0.00 19085, respectively). In order to ascertain the characteristics and evolution of mating patterns in Gredos, the contribution of each degree of kinship was analyzed as a whole and then for each valley separately. Regarding total consanguineous marriages in Gredos, there is a low frequency of uncle-niece matings (0.21%) and a first-second cousin mating ratio (C22/C33) of 0.23 (up to the third degree of consanguinity). Before 1918 multiple matings (i.e., those involving more than a single relationship) accounted for 19.16% of consanguineous marriages (up to the fourth degree). The observed frequencies of multiple consanguineous marriages was, on average, about twice that expected at random, and the proportion of such marriages to total inbreeding was 34.65%. The temporal change of the Gredos inbreeding pattern was characterized by a recent decrease; the highest inbreeding levels correspond to the period from 1915 to 1944. Finally, intervalley differences (maximum inbreeding coefficient in the Tormes, minimum in the Tietar) are interpreted considering the geography, population size, and population mobility for each valley
@article{
title = {Inbreeding in Gredos mountain range (Spain): contribution of multiple consanguinity and intervalley variation},
type = {article},
year = {2001},
identifiers = {[object Object]},
keywords = {*Consanguinity,Ethnic Groups/*genetics,Geography,Human,Probability,Socioeconomic Factors,Spain,Support, Non-U.S. Gov't,Time Factors},
pages = {249-70.},
volume = {73},
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abstract = {The present paper examines consanguineous marriages occurring between 1874 and 1975 in three valleys (Tormes, Alberche, and Tietar) in the Sierra de Gredos mountain range, Avila province, Spain. Information was obtained from parish registers of 42 localities, corresponding to a total of 41,696 weddings. Consanguineous marriages were defined as those up to the third degree of consanguinity (second cousins). From 1874 to 1975 the percentage of related mates was 4.45% and the inbreeding coefficient was 0.0011868 (for 1874 to 1917 corresponding figures up to the fourth degree were 16.44% and 0.00 19085, respectively). In order to ascertain the characteristics and evolution of mating patterns in Gredos, the contribution of each degree of kinship was analyzed as a whole and then for each valley separately. Regarding total consanguineous marriages in Gredos, there is a low frequency of uncle-niece matings (0.21%) and a first-second cousin mating ratio (C22/C33) of 0.23 (up to the third degree of consanguinity). Before 1918 multiple matings (i.e., those involving more than a single relationship) accounted for 19.16% of consanguineous marriages (up to the fourth degree). The observed frequencies of multiple consanguineous marriages was, on average, about twice that expected at random, and the proportion of such marriages to total inbreeding was 34.65%. The temporal change of the Gredos inbreeding pattern was characterized by a recent decrease; the highest inbreeding levels correspond to the period from 1915 to 1944. Finally, intervalley differences (maximum inbreeding coefficient in the Tormes, minimum in the Tietar) are interpreted considering the geography, population size, and population mobility for each valley},
bibtype = {article},
author = {Fuster, V and Jimenez, A M and Colantonio, S E},
journal = {Hum Biol},
number = {2}
}Activation of the auditory pre-attentive change detection system by tone repetitions with fast stimulation rate. Wolff, C & Schröger, E Brain Res Cogn Brain Res, 10(3):323-7, 2001.
abstract bibtex
abstract bibtex
The human automatic pre-attentive change detection system indexed by the mismatch negativity (MMN) component of the auditory event-related brain potential is known to be highly adaptive. The present study showed that even infrequent repetitions of tones can elicit MMN, independently of attention, when tones of varying frequency are rapidly presented in an isochronous rhythm. This demonstrates that frequency variation can be extracted as an invariant feature of the acoustic environment revealing the capacity for adaptation of the auditory pre-attentive change detection system. It is argued that this capacity is related to the temporal-window of integration.
@Article{Wolff2001,
author = {C Wolff and E Schr\"oger},
journal = {Brain Res Cogn Brain Res},
title = {Activation of the auditory pre-attentive change detection system by tone repetitions with fast stimulation rate.},
year = {2001},
number = {3},
pages = {323-7},
volume = {10},
abstract = {The human automatic pre-attentive change detection system indexed
by the mismatch negativity (MMN) component of the auditory event-related
brain potential is known to be highly adaptive. The present study
showed that even infrequent repetitions of tones can elicit MMN,
independently of attention, when tones of varying frequency are rapidly
presented in an isochronous rhythm. This demonstrates that frequency
variation can be extracted as an invariant feature of the acoustic
environment revealing the capacity for adaptation of the auditory
pre-attentive change detection system. It is argued that this capacity
is related to the temporal-window of integration.},
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}Unsupervised statistical learning of higher-order spatial structures from visual scenes. Fiser, J & Aslin, R. N Psychol Sci, 12(6):499-504, 2001.
abstract bibtex
abstract bibtex
Three experiments investigated the ability of human observers to extract the joint and conditional probabilities of shape co-occurrences during passive viewing of complex visual scenes. Results indicated that statistical learning of shape conjunctions was both rapid and automatic, as subjects were not instructed to attend to any particularfeatures of the displays. Moreover, in addition to single-shape frequency, subjects acquired in parallel several different higher-order aspects of the statistical structure of the displays, including absolute shape-position relations in an array, shape-pair arrangements independent of position, and conditional probabilities of shape co-occurrences. Unsupervised learning of these higher-order statistics provides support for Barlow's theory of visual recognition, which posits that detecting "suspicious coincidences" of elements during recognition is a necessary prerequisite for efficient learning of new visual features.
@Article{Fiser2001,
author = {J Fiser and Richard N Aslin},
journal = {Psychol Sci},
title = {Unsupervised statistical learning of higher-order spatial structures from visual scenes.},
year = {2001},
number = {6},
pages = {499-504},
volume = {12},
abstract = {Three experiments investigated the ability of human observers to extract
the joint and conditional probabilities of shape co-occurrences during
passive viewing of complex visual scenes. Results indicated that
statistical learning of shape conjunctions was both rapid and automatic,
as subjects were not instructed to attend to any particularfeatures
of the displays. Moreover, in addition to single-shape frequency,
subjects acquired in parallel several different higher-order aspects
of the statistical structure of the displays, including absolute
shape-position relations in an array, shape-pair arrangements independent
of position, and conditional probabilities of shape co-occurrences.
Unsupervised learning of these higher-order statistics provides support
for Barlow's theory of visual recognition, which posits that detecting
"suspicious coincidences" of elements during recognition is a necessary
prerequisite for efficient learning of new visual features.},
keywords = {Computing Methodologies, Human, Language, Learning, Mental Processes, Models, Theoretical, Stochastic Processes, Support, U.S. Gov't, Non-P.H.S., Cognition, Linguistics, Neural Networks (Computer), Practice (Psychology), Non-U.S. Gov't, Memory, Psychological, Task Performance and Analysis, Time Factors, Visual Perception, Adult, Attention, Discrimination Learning, Female, Male, Short-Term, Mental Recall, Orientation, Pattern Recognition, Visual, Perceptual Masking, Reading, Concept Formation, Form Perception, Animals, Corpus Striatum, Shrews, P.H.S., Visual Cortex, Visual Pathways, Acoustic Stimulation, Auditory Cortex, Auditory Perception, Cochlea, Ear, Gerbillinae, Glycine, Hearing, Neurons, Space Perception, Strychnine, Adolescent, Decision Making, Reaction Time, Astrocytoma, Brain Mapping, Brain Neoplasms, Cerebral Cortex, Electric Stimulation, Electrophysiology, Epilepsy, Temporal Lobe, Evoked Potentials, Frontal Lobe, Noise, Parietal Lobe, Scalp, Child, Language Development, Psycholinguistics, Brain, Perception, Speech, Vocalization, Animal, Discrimination (Psychology), Hippocampus, Rats, Calcium, Chelating Agents, Excitatory Postsynaptic Potentials, Glutamic Acid, Guanosine Diphosphate, In Vitro, Neuronal Plasticity, Pyramidal Cells, Receptors, AMPA, Metabotropic Glutamate, N-Methyl-D-Aspartate, Somatosensory Cortex, Synapses, Synaptic Transmission, Thionucleotides, Action Potentials, Calcium Channels, L-Type, Electric Conductivity, Entorhinal Cortex, Neurological, Long-Evans, Infant, Mathematics, Statistics, Probability Learning, Problem Solving, Psychophysics, 11760138},
}Objects and attention: The state of the art. Scholl, B. J. Cognition, 80(1-2):1-46, 2001.
abstract bibtex
abstract bibtex
What are the units of attention? In addition to standard models holding that attention can select spatial regions and visual features, recent work suggests that in some cases attention can directly select discrete objects. This paper reviews the state of the art with regard to such 'object-based' attention, and explores how objects of attention relate to locations, reference frames, perceptual groups, surfaces, parts, and features. Also discussed are the dynamic aspects of objecthood, including the question of how attended objects are individuated in time, and the possibility of attending to simple dynamic motions and events. The final sections of this review generalize these issues beyond vision science, to other modalities and fields such as auditory objects of attention and the infant's 'object concept'.
@Article{Scholl2001b,
author = {B. J. Scholl},
journal = {Cognition},
title = {Objects and attention: {T}he state of the art.},
year = {2001},
number = {1-2},
pages = {1-46},
volume = {80},
abstract = {What are the units of attention? In addition to standard models holding
that attention can select spatial regions and visual features, recent
work suggests that in some cases attention can directly select discrete
objects. This paper reviews the state of the art with regard to such
'object-based' attention, and explores how objects of attention relate
to locations, reference frames, perceptual groups, surfaces, parts,
and features. Also discussed are the dynamic aspects of objecthood,
including the question of how attended objects are individuated in
time, and the possibility of attending to simple dynamic motions
and events. The final sections of this review generalize these issues
beyond vision science, to other modalities and fields such as auditory
objects of attention and the infant's 'object concept'.},
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}2000 (6)
In vivo penetration of experimentally produced clots by monoclonal antibodies. McEvoy, F., J., Edgell, T., A., Webbon, P., M., & Gaffney, P., J. Thrombosis and haemostasis, 83(6):882-886, 6, 2000.
abstract bibtex
abstract bibtex
Antifibrin monoclonal antibodies show potential as clot targeting agents for diagnosis and possibly therapy in thrombotic disease. To be effective the antibody must bind to the fibrin component of the clot. The ability of two antifibrin mabs (NIB 1H10 and NIB 12B3) to penetrate occlusive clots in vivo was investigated. Both mabs react with human fibrin but not with human fibrinogen nor with the fibrin or fibrinogen from the species used in this study. Two heterologous animal (sheep and rabbit) thrombus models were used. Clots in both cases were made within isolated vein segments using a mixture of human and native fibrinogen. The clots in sheep veins were observed radiographically and found to be occlusive for a mean of 4.2 +/- 2.2 days and thereafter appeared only partially occlusive. When targeted in their occlusive phase (131)I labelled mab accumulated in the clot reaching a maximum ratio of 1.82 +/- 0.42 when compared to counts in homologous sheep clots in the contralateral limb. It was confirmed in the rabbit jugular vein model that total occlusivity did not prevent antibody accumulation in the heterologous clot by injecting the fibrin specific mab 1H10 and examining the clot excised after 1, 6 and 24 h using immunofluorescence. In a further series of similar experiments (125)I labelled mab 1H10 was used and detected using autoradiography. Both sets of experiments indicated that penetration of occlusive clots by the antibody occurred and that considerable accumulation was present at 6 and 24 h. The results indicate that a circulating antibody can readily gain access to experimentally produced clots in occluded veins.
@article{
title = {In vivo penetration of experimentally produced clots by monoclonal antibodies},
type = {article},
year = {2000},
identifiers = {[object Object]},
keywords = {Animals,Antibodies, Monoclonal/metabolism,Antibody Specificity,Autoradiography,Blood Coagulation/immunology,Disease Models, Animal,Fibrin/immunology,Fluorescent Antibody Technique,Humans,Immunoglobulin G/metabolism,Iodine Radioisotopes/diagnostic use,Jugular Veins/pathology,Phlebography,Protein Binding,Rabbits,Saphenous Vein/pathology,Sheep,Thrombosis/immunology/radiography,Time Factors},
pages = {882-886},
volume = {83},
month = {6},
city = {Royal Veterinary College, Hatfield, UK. f.mcevoy@swipnet.se},
id = {e17cc696-c7cd-3a2f-822a-fbb9eea6c336},
created = {2016-09-06T13:34:39.000Z},
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authored = {true},
confirmed = {true},
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source_type = {JOUR},
notes = {LR: 20041117; PUBM: Print; JID: 7608063; 0 (Antibodies, Monoclonal); 0 (Immunoglobulin G); 0 (Iodine Radioisotopes); 9001-31-4 (Fibrin); ppublish},
abstract = {Antifibrin monoclonal antibodies show potential as clot targeting agents for diagnosis and possibly therapy in thrombotic disease. To be effective the antibody must bind to the fibrin component of the clot. The ability of two antifibrin mabs (NIB 1H10 and NIB 12B3) to penetrate occlusive clots in vivo was investigated. Both mabs react with human fibrin but not with human fibrinogen nor with the fibrin or fibrinogen from the species used in this study. Two heterologous animal (sheep and rabbit) thrombus models were used. Clots in both cases were made within isolated vein segments using a mixture of human and native fibrinogen. The clots in sheep veins were observed radiographically and found to be occlusive for a mean of 4.2 +/- 2.2 days and thereafter appeared only partially occlusive. When targeted in their occlusive phase (131)I labelled mab accumulated in the clot reaching a maximum ratio of 1.82 +/- 0.42 when compared to counts in homologous sheep clots in the contralateral limb. It was confirmed in the rabbit jugular vein model that total occlusivity did not prevent antibody accumulation in the heterologous clot by injecting the fibrin specific mab 1H10 and examining the clot excised after 1, 6 and 24 h using immunofluorescence. In a further series of similar experiments (125)I labelled mab 1H10 was used and detected using autoradiography. Both sets of experiments indicated that penetration of occlusive clots by the antibody occurred and that considerable accumulation was present at 6 and 24 h. The results indicate that a circulating antibody can readily gain access to experimentally produced clots in occluded veins.},
bibtype = {article},
author = {McEvoy, F J and Edgell, T A and Webbon, P M and Gaffney, P J},
journal = {Thrombosis and haemostasis},
number = {6}
}Learning of action through adaptive combination of motor primitives. Thoroughman, K. & Shadmehr, R Nature, 407(6805):742-7, 2000.
doi abstract bibtex
doi abstract bibtex
Understanding how the brain constructs movements remains a fundamental challenge in neuroscience. The brain may control complex movements through flexible combination of motor primitives, where each primitive is an element of computation in the sensorimotor map that transforms desired limb trajectories into motor commands. Theoretical studies have shown that a system's ability to learn action depends on the shape of its primitives. Using a time-series analysis of error patterns, here we show that humans learn the dynamics of reaching movements through a flexible combination of primitives that have gaussian-like tuning functions encoding hand velocity. The wide tuning of the inferred primitives predicts limitations on the brain's ability to represent viscous dynamics. We find close agreement between the predicted limitations and the subjects' adaptation to new force fields. The mathematical properties of the derived primitives resemble the tuning curves of Purkinje cells in the cerebellum. The activity of these cells may encode primitives that underlie the learning of dynamics.
@Article{Thoroughman2000,
author = {KA Thoroughman and R Shadmehr},
journal = {Nature},
title = {Learning of action through adaptive combination of motor primitives.},
year = {2000},
number = {6805},
pages = {742-7},
volume = {407},
abstract = {Understanding how the brain constructs movements remains a fundamental
challenge in neuroscience. The brain may control complex movements
through flexible combination of motor primitives, where each primitive
is an element of computation in the sensorimotor map that transforms
desired limb trajectories into motor commands. Theoretical studies
have shown that a system's ability to learn action depends on the
shape of its primitives. Using a time-series analysis of error patterns,
here we show that humans learn the dynamics of reaching movements
through a flexible combination of primitives that have gaussian-like
tuning functions encoding hand velocity. The wide tuning of the inferred
primitives predicts limitations on the brain's ability to represent
viscous dynamics. We find close agreement between the predicted limitations
and the subjects' adaptation to new force fields. The mathematical
properties of the derived primitives resemble the tuning curves of
Purkinje cells in the cerebellum. The activity of these cells may
encode primitives that underlie the learning of dynamics.},
doi = {10.1038/35037588},
keywords = {Computing Methodologies, Human, Language, Learning, Mental Processes, Models, Theoretical, Stochastic Processes, Support, U.S. Gov't, Non-P.H.S., Cognition, Linguistics, Neural Networks (Computer), Practice (Psychology), Non-U.S. Gov't, Memory, Psychological, Task Performance and Analysis, Time Factors, Visual Perception, Adult, Attention, Discrimination Learning, Female, Male, Short-Term, Mental Recall, Orientation, Pattern Recognition, Visual, Perceptual Masking, Reading, Concept Formation, Form Perception, Animals, Corpus Striatum, Shrews, P.H.S., Visual Cortex, Visual Pathways, Acoustic Stimulation, Auditory Cortex, Auditory Perception, Cochlea, Ear, Gerbillinae, Glycine, Hearing, Neurons, Space Perception, Strychnine, Adolescent, Decision Making, Reaction Time, Astrocytoma, Brain Mapping, Brain Neoplasms, Cerebral Cortex, Electric Stimulation, Electrophysiology, Epilepsy, Temporal Lobe, Evoked Potentials, Frontal Lobe, Noise, Parietal Lobe, Scalp, Child, Language Development, Psycholinguistics, Brain, Perception, Speech, Vocalization, Animal, Discrimination (Psychology), Hippocampus, Rats, Calcium, Chelating Agents, Excitatory Postsynaptic Potentials, Glutamic Acid, Guanosine Diphosphate, In Vitro, Neuronal Plasticity, Pyramidal Cells, Receptors, AMPA, Metabotropic Glutamate, N-Methyl-D-Aspartate, Somatosensory Cortex, Synapses, Synaptic Transmission, Thionucleotides, Action Potentials, Calcium Channels, L-Type, Electric Conductivity, Entorhinal Cortex, Neurological, Long-Evans, Infant, Mathematics, Statistics, Probability Learning, Problem Solving, Psychophysics, Association Learning, Child Psychology, Habituation (Psychophysiology), Probability Theory, Analysis of Variance, Semantics, Symbolism, Behavior, Eye Movements, Macaca mulatta, Prefrontal Cortex, Cats, Dogs, Haplorhini, Photic Stimulation, Electroencephalography, Nervous System Physiology, Darkness, Grasshoppers, Light, Membrane Potentials, Neural Inhibition, Afferent, Picrotoxin, Vision, Deoxyglucose, Injections, Microspheres, Neural Pathways, Rhodamines, Choice Behavior, Speech Perception, Verbal Learning, Dominance, Cerebral, Fixation, Ocular, Language Tests, Random Allocation, Comparative Study, Saguinus, Sound Spectrography, Species Specificity, Audiometry, Auditory Threshold, Calibration, Data Interpretation, Statistical, Anesthesia, General, Electrodes, Implanted, Pitch Perception, Sound Localization, Paired-Associate Learning, Serial Learning, Auditory, Age Factors, Motion Perception, Brain Injuries, Computer Simulation, Blindness, Psychomotor Performance, Color Perception, Signal Detection (Psychology), Judgment, ROC Curve, Regression Analysis, Music, Probability, Arm, Cerebrovascular Disorders, Hemiplegia, Movement, Muscle, Skeletal, Myoclonus, Robotics, Magnetoencephalography, Phonetics, Software, Speech Production Measurement, Epilepsies, Partial, Laterality, Stereotaxic Techniques, Germany, Speech Acoustics, Verbal Behavior, Child Development, Instinct, Brain Stem, Coma, Diagnosis, Differential, Hearing Disorders, Hearing Loss, Central, Neuroma, Acoustic, Dendrites, Down-Regulation, Patch-Clamp Techniques, Wistar, Up-Regulation, Aged, Aphasia, Middle Aged, Cones (Retina), Primates, Retina, Retinal Ganglion Cells, Tympanic Membrane, Cell Communication, Extremities, Biological, Motor Activity, Rana catesbeiana, Spinal Cord, Central Nervous System, Motion, Motor Cortex, Intelligence, Macaca fascicularis, Adoption, Critical Period (Psychology), France, Korea, Magnetic Resonance Imaging, Multilingualism, Auditory Pathways, Cochlear Nerve, Loudness Perception, Neural Conduction, Sensory Thresholds, Sound, Language Disorders, Preschool, Generalization (Psychology), Vocabulary, Biophysics, Nerve Net, Potassium Channels, Sodium Channels, Cues, Differential Threshold, Arousal, Newborn, Sucking Behavior, Ferrets, Microelectrodes, Gestalt Theory, Mathematical Computing, Perceptual Closure, Vestibulocochlear Nerve, Brain Damage, Chronic, Regional Blood Flow, Thinking, Tomography, Emission-Computed, Case-Control Studies, Multivariate Analysis, Artificial Intelligence, Depth Perception, 11048700},
}Risk of venous thromboembolism among users of third generation oral contraceptives compared with users of oral contraceptives with levonorgestrel before and after 1995: cohort and case-control analysis. Jick, H., Kaye, J. A., Vasilakis-Scaramozza, C., & Jick, S. S. BMJ (Clinical research ed.), 321(7270):1190--1195, November, 2000.
abstract bibtex
abstract bibtex
OBJECTIVE: To compare the risk of idiopathic venous thromboembolism among women taking third generation oral contraceptives (with gestodene or desogestrel) with that among women taking oral contraceptives with levonorgestrel. DESIGN: Cohort and case-control analyses derived from the General Practice Research Database. SETTING: UK general practices, January 1993 to December 1999. PARTICIPANTS: Women aged 15-39 taking third generation oral contraceptives or oral contraceptives with levonorgestrel. MAIN OUTCOME MEASURES: Relative incidence (cohort study) and odds ratios (case-control study) as measures of the relative risk of venous thromboembolism. RESULTS: The adjusted estimates of relative risk for venous thromboembolism associated with third generation oral contraceptives compared with oral contraceptives with levonorgestrel was 1.9 (95% confidence interval 1.3 to 2.8) in the cohort analysis and 2.3 (1.3 to 3.9) in the case-control study. The estimates for the two types of oral contraceptives were similar before and after the warning issued by the Committee on Safety of Medicines in October 1995. A shift away from the use of third generation oral contraceptives after the scare was more pronounced among younger women (who have a lower risk of venous thromboembolism) than among older women. Fewer cases of venous thromboembolism occurred in 1996 and later than would have been expected if the use of oral contraceptives had remained unchanged. CONCLUSIONS: These findings are consistent with previously reported studies, which found that compared with oral contraceptives with levonorgestrel, third generation oral contraceptives are associated with around twice the risk of venous thromboembolism.
@article{jick_risk_2000-1,
title = {Risk of venous thromboembolism among users of third generation oral contraceptives compared with users of oral contraceptives with levonorgestrel before and after 1995: cohort and case-control analysis},
volume = {321},
issn = {0959-8138},
shorttitle = {Risk of venous thromboembolism among users of third generation oral contraceptives compared with users of oral contraceptives with levonorgestrel before and after 1995},
abstract = {OBJECTIVE: To compare the risk of idiopathic venous thromboembolism among women taking third generation oral contraceptives (with gestodene or desogestrel) with that among women taking oral contraceptives with levonorgestrel.
DESIGN: Cohort and case-control analyses derived from the General Practice Research Database.
SETTING: UK general practices, January 1993 to December 1999.
PARTICIPANTS: Women aged 15-39 taking third generation oral contraceptives or oral contraceptives with levonorgestrel.
MAIN OUTCOME MEASURES: Relative incidence (cohort study) and odds ratios (case-control study) as measures of the relative risk of venous thromboembolism.
RESULTS: The adjusted estimates of relative risk for venous thromboembolism associated with third generation oral contraceptives compared with oral contraceptives with levonorgestrel was 1.9 (95\% confidence interval 1.3 to 2.8) in the cohort analysis and 2.3 (1.3 to 3.9) in the case-control study. The estimates for the two types of oral contraceptives were similar before and after the warning issued by the Committee on Safety of Medicines in October 1995. A shift away from the use of third generation oral contraceptives after the scare was more pronounced among younger women (who have a lower risk of venous thromboembolism) than among older women. Fewer cases of venous thromboembolism occurred in 1996 and later than would have been expected if the use of oral contraceptives had remained unchanged.
CONCLUSIONS: These findings are consistent with previously reported studies, which found that compared with oral contraceptives with levonorgestrel, third generation oral contraceptives are associated with around twice the risk of venous thromboembolism.},
language = {eng},
number = {7270},
journal = {BMJ (Clinical research ed.)},
author = {Jick, H. and Kaye, J. A. and Vasilakis-Scaramozza, C. and Jick, S. S.},
month = nov,
year = {2000},
pmid = {11073511},
pmcid = {PMC27524},
keywords = {Adolescent, Adult, Age Distribution, Body Mass Index, Case-Control Studies, Cohort Studies, Contraceptives, Oral, Contraceptives, Oral, Synthetic, Female, Humans, Levonorgestrel, Odds Ratio, Risk Factors, Smoking, Thromboembolism, Time Factors},
pages = {1190--1195}
}Stress grouping improves performance on an immediate serial list recall task. Reeves, C., Schmauder, A. R., & Morris, R. K. J Exp Psychol Learn Mem Cogn, 26(6):1638-54, 2000.
abstract bibtex
abstract bibtex
Five experiments investigated whether perceptual patterning afforded by imposing a recurrent stress pattern on auditorially presented lists has a positive effect on list recall. The experiments also addressed whether the recall advantage reflected the salience that the stress pattern created for certain items or whether the recall advantage arose from the distinct grouping configurations that were produced by the stress pattern. The authors explored these issues by examining immediate serial-recall performance for spoken lists that either did or did not have a stress pattern imposed on them. Lists had an anapest or dactylic stress pattern or were monotone and consisted of two stimulus types, either digit names or common English nouns. Results showed that stress patterns enhanced serial-recall performance and that the recall benefit derived primarily from the perceptual grouping afforded by the stress patterns. Results also showed that the grouping benefit derived from stress patterning generalizes to monotone lists. In contrast, salience effects are attached to the stimulus per se and do not transfer.
@Article{Reeves2000,
author = {C. Reeves and A. R. Schmauder and R. K. Morris},
journal = {J Exp Psychol Learn Mem Cogn},
title = {Stress grouping improves performance on an immediate serial list recall task.},
year = {2000},
number = {6},
pages = {1638-54},
volume = {26},
abstract = {Five experiments investigated whether perceptual patterning afforded
by imposing a recurrent stress pattern on auditorially presented
lists has a positive effect on list recall. The experiments also
addressed whether the recall advantage reflected the salience that
the stress pattern created for certain items or whether the recall
advantage arose from the distinct grouping configurations that were
produced by the stress pattern. The authors explored these issues
by examining immediate serial-recall performance for spoken lists
that either did or did not have a stress pattern imposed on them.
Lists had an anapest or dactylic stress pattern or were monotone
and consisted of two stimulus types, either digit names or common
English nouns. Results showed that stress patterns enhanced serial-recall
performance and that the recall benefit derived primarily from the
perceptual grouping afforded by the stress patterns. Results also
showed that the grouping benefit derived from stress patterning generalizes
to monotone lists. In contrast, salience effects are attached to
the stimulus per se and do not transfer.},
keywords = {Adult, Auditory Perception, Female, Humans, Male, Mental Processes, Mental Recall, Psychological, Stress, Time Factors, 11185787},
}Order information in working memory: fMRI evidence for parietal and prefrontal mechanisms. Marshuetz, C., Smith, E. E., Jonides, J., DeGutis, J., & Chenevert, T. L. J Cogn Neurosci, 12 Suppl 2:130-44, 2000.
doi abstract bibtex
doi abstract bibtex
Working memory is thought to include a mechanism that allows for the coding of order information. One question of interest is how order information is coded, and how that code is neurally implemented. Here we report both behavioral and fMRI findings from an experiment involved comparing two tasks, an item-memory task and an order-memory task. In each case, five letters were presented for storage, followed after a brief interval by a set of probe letters. In the case of the item-memory task, the two letters were identical, and the subject responded to the question, "Was this letter one of the items you saw?". In the case of the order-memory task, the letters were different, and subjects responded to the question, "Are these two letters in the order in which you saw them?". Behaviorally, items that were further apart in the sequence that elicited faster reaction times and higher accuracy in the Order task. Areas that were significantly more activated in the Order condition included the parietal and prefrontal cortex. Parietal activations overlapped those involved in number processing, leading to the suggestion that the underlying representation of order and numbers may share a common process, coding for magnitude.
@Article{Marshuetz2000,
author = {C. Marshuetz and E. E. Smith and J. Jonides and J. DeGutis and T. L. Chenevert},
journal = {J Cogn Neurosci},
title = {Order information in working memory: f{MRI} evidence for parietal and prefrontal mechanisms.},
year = {2000},
pages = {130-44},
volume = {12 Suppl 2},
abstract = {Working memory is thought to include a mechanism that allows for the
coding of order information. One question of interest is how order
information is coded, and how that code is neurally implemented.
Here we report both behavioral and fMRI findings from an experiment
involved comparing two tasks, an item-memory task and an order-memory
task. In each case, five letters were presented for storage, followed
after a brief interval by a set of probe letters. In the case of
the item-memory task, the two letters were identical, and the subject
responded to the question, "Was this letter one of the items you
saw?". In the case of the order-memory task, the letters were different,
and subjects responded to the question, "Are these two letters in
the order in which you saw them?". Behaviorally, items that were
further apart in the sequence that elicited faster reaction times
and higher accuracy in the Order task. Areas that were significantly
more activated in the Order condition included the parietal and prefrontal
cortex. Parietal activations overlapped those involved in number
processing, leading to the suggestion that the underlying representation
of order and numbers may share a common process, coding for magnitude.},
doi = {10.1162/08989290051137459},
keywords = {Brain Mapping, Cognition, Female, Functional Laterality, Humans, Magnetic Resonance Imaging, Male, Memory, Parietal Lobe, Pattern Recognition, Prefrontal Cortex, Reaction Time, Short-Term, Time Factors, Visual, 11506653},
}The Chk1 protein kinase and the Cdc25C regulatory pathways are targets of the anticancer agent UCN-01. Graves, P. R., Yu, L., Schwarz, J. K., Gales, J., Sausville, E. A., O'Connor, P. M., & Piwnica-Worms, H. The Journal of Biological Chemistry, 275(8):5600–5605, February, 2000.
abstract bibtex
abstract bibtex
A checkpoint operating in the G(2) phase of the cell cycle prevents entry into mitosis in the presence of DNA damage. UCN-01, a protein kinase inhibitor currently undergoing clinical trials for cancer treatment, abrogates G(2) checkpoint function and sensitizes p53-defective cancer cells to DNA-damaging agents. In most species, the G(2) checkpoint prevents the Cdc25 phosphatase from removing inhibitory phosphate groups from the mitosis-promoting kinase Cdc2. This is accomplished by maintaining Cdc25 in a phosphorylated form that binds 14-3-3 proteins. The checkpoint kinases, Chk1 and Cds1, are proposed to regulate the interactions between human Cdc25C and 14-3-3 proteins by phosphorylating Cdc25C on serine 216. 14-3-3 proteins, in turn, function to keep Cdc25C out of the nucleus. Here we report that UCN-01 caused loss of both serine 216 phosphorylation and 14-3-3 binding to Cdc25C in DNA-damaged cells. In addition, UCN-01 potently inhibited the ability of Chk1 to phosphorylate Cdc25C in vitro. In contrast, Cds1 was refractory to inhibition by UCN-01 in vitro, and Cds1 was still phosphorylated in irradiated cells treated with UCN-01. Thus, neither Cds1 nor kinases upstream of Cds1, such as ataxia telangiectasia-mutated, are targets of UCN-01 action in vivo. Taken together our results identify the Chk1 kinase and the Cdc25C pathway as potential targets of G(2) checkpoint abrogation by UCN-01.
@article{graves_chk1_2000,
title = {The {Chk1} protein kinase and the {Cdc25C} regulatory pathways are targets of the anticancer agent {UCN}-01},
volume = {275},
issn = {0021-9258},
abstract = {A checkpoint operating in the G(2) phase of the cell cycle prevents entry into mitosis in the presence of DNA damage. UCN-01, a protein kinase inhibitor currently undergoing clinical trials for cancer treatment, abrogates G(2) checkpoint function and sensitizes p53-defective cancer cells to DNA-damaging agents. In most species, the G(2) checkpoint prevents the Cdc25 phosphatase from removing inhibitory phosphate groups from the mitosis-promoting kinase Cdc2. This is accomplished by maintaining Cdc25 in a phosphorylated form that binds 14-3-3 proteins. The checkpoint kinases, Chk1 and Cds1, are proposed to regulate the interactions between human Cdc25C and 14-3-3 proteins by phosphorylating Cdc25C on serine 216. 14-3-3 proteins, in turn, function to keep Cdc25C out of the nucleus. Here we report that UCN-01 caused loss of both serine 216 phosphorylation and 14-3-3 binding to Cdc25C in DNA-damaged cells. In addition, UCN-01 potently inhibited the ability of Chk1 to phosphorylate Cdc25C in vitro. In contrast, Cds1 was refractory to inhibition by UCN-01 in vitro, and Cds1 was still phosphorylated in irradiated cells treated with UCN-01. Thus, neither Cds1 nor kinases upstream of Cds1, such as ataxia telangiectasia-mutated, are targets of UCN-01 action in vivo. Taken together our results identify the Chk1 kinase and the Cdc25C pathway as potential targets of G(2) checkpoint abrogation by UCN-01.},
language = {eng},
number = {8},
journal = {The Journal of Biological Chemistry},
author = {Graves, P. R. and Yu, L. and Schwarz, J. K. and Gales, J. and Sausville, E. A. and O'Connor, P. M. and Piwnica-Worms, H.},
month = feb,
year = {2000},
keywords = {Alkaloids, Antineoplastic Agents, Cell Cycle Proteins, Checkpoint Kinase 1, Checkpoint Kinase 2, Cloning, Molecular, DNA Damage, Dose-Response Relationship, Radiation, G2 Phase, HeLa Cells, Humans, Membrane Proteins, Models, Biological, Phosphorylation, Plasmids, Protein Kinase Inhibitors, Protein Kinases, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Serine, Staurosporine, Time Factors, cdc25 Phosphatases},
pages = {5600--5605},
}1999 (2)
Do infants learn grammar with algebra or statistics?. Eimas, P. Science, 284(5413):435-6; author reply 436-7, 1999.
bibtex
bibtex
@Article{Eimas1999,
author = {PD Eimas},
journal = {Science},
title = {Do infants learn grammar with algebra or statistics?},
year = {1999},
number = {5413},
pages = {435-6; author reply 436-7},
volume = {284},
keywords = {Computing Methodologies, Human, Language, Learning, Mental Processes, Models, Theoretical, Stochastic Processes, Support, U.S. Gov't, Non-P.H.S., Cognition, Linguistics, Neural Networks (Computer), Practice (Psychology), Non-U.S. Gov't, Memory, Psychological, Task Performance and Analysis, Time Factors, Visual Perception, Adult, Attention, Discrimination Learning, Female, Male, Short-Term, Mental Recall, Orientation, Pattern Recognition, Visual, Perceptual Masking, Reading, Concept Formation, Form Perception, Animals, Corpus Striatum, Shrews, P.H.S., Visual Cortex, Visual Pathways, Acoustic Stimulation, Auditory Cortex, Auditory Perception, Cochlea, Ear, Gerbillinae, Glycine, Hearing, Neurons, Space Perception, Strychnine, Adolescent, Decision Making, Reaction Time, Astrocytoma, Brain Mapping, Brain Neoplasms, Cerebral Cortex, Electric Stimulation, Electrophysiology, Epilepsy, Temporal Lobe, Evoked Potentials, Frontal Lobe, Noise, Parietal Lobe, Scalp, Child, Language Development, Psycholinguistics, Brain, Perception, Speech, Vocalization, Animal, Discrimination (Psychology), Hippocampus, Rats, Calcium, Chelating Agents, Excitatory Postsynaptic Potentials, Glutamic Acid, Guanosine Diphosphate, In Vitro, Neuronal Plasticity, Pyramidal Cells, Receptors, AMPA, Metabotropic Glutamate, N-Methyl-D-Aspartate, Somatosensory Cortex, Synapses, Synaptic Transmission, Thionucleotides, Action Potentials, Calcium Channels, L-Type, Electric Conductivity, Entorhinal Cortex, Neurological, Long-Evans, Infant, Mathematics, Statistics, 9872745},
}Genetic epidemiology of single-nucleotide polymorphisms. Collins, A., Lonjou, C., & Morton, N., E. Proc Natl Acad Sci U S A, 96(26):15173-7., 1999.
Paper abstract bibtex
Paper abstract bibtex On the causal hypothesis, most genetic determinants of disease are single-nucleotide polymorphisms (SNPs) that are likely to be selected as markers for positional cloning. On the proximity hypothesis, most disease determinants will not be included among markers but may be detected through linkage disequilibrium with other SNPs. In that event, allelic association among SNPs is an essential factor in positional cloning. Recent simulation based on monotonic population expansion suggests that useful association does not usually extend beyond 3 kb. This is contradicted by significant disequilibrium at much greater distances, with corresponding reduction in the number of SNPs required for a cost-effective genome scan. A plausible explanation is that cyclical expansions follow population bottlenecks that establish new disequilibria. Data on more than 1,000 locus pairs indicate that most disequilibria trace to the Neolithic, with no apparent difference between haplotypes that are random or selected through a major disease gene. Short duration may be characteristic of alleles contributing to disease susceptibility and haplotypes characteristic of particular ethnic groups. Alleles that are highly polymorphic in all ethnic groups may be older, neutral, or advantageous, in weak disequilibrium with nearby markers, and therefore less useful for positional cloning of disease genes. Significant disequilibrium at large distance makes the number of suitably chosen SNPs required for genome screening as small as 30,000, or 1 per 100 kb, with greater density (including less common SNPs) reserved for candidate regions.
@article{
title = {Genetic epidemiology of single-nucleotide polymorphisms},
type = {article},
year = {1999},
identifiers = {[object Object]},
keywords = {*Evolution, Molecular,*Genetic Predisposition to Disease,*Linkage Disequilibrium,*Polymorphism, Restriction Fragment Length,Case-Control Studies,Chromosome Mapping,Cloning, Molecular/*methods,Gene Frequency,Genetic Heterogeneity,Haplotypes,Human,Racial Stocks/genetics,Time Factors},
pages = {15173-7.},
volume = {96},
id = {a6d87bce-f6a5-33f5-ae51-cbff9129ea59},
created = {2017-06-19T13:45:32.210Z},
file_attached = {true},
profile_id = {de68dde1-2ff3-3a4e-a214-ef424d0c7646},
group_id = {b2078731-0913-33b9-8902-a53629a24e83},
last_modified = {2017-06-19T13:45:32.339Z},
tags = {02/12/05},
read = {false},
starred = {false},
authored = {false},
confirmed = {true},
hidden = {false},
source_type = {Journal Article},
notes = {<m:note>eng<m:linebreak/>Journal Article</m:note>},
abstract = {On the causal hypothesis, most genetic determinants of disease are single-nucleotide polymorphisms (SNPs) that are likely to be selected as markers for positional cloning. On the proximity hypothesis, most disease determinants will not be included among markers but may be detected through linkage disequilibrium with other SNPs. In that event, allelic association among SNPs is an essential factor in positional cloning. Recent simulation based on monotonic population expansion suggests that useful association does not usually extend beyond 3 kb. This is contradicted by significant disequilibrium at much greater distances, with corresponding reduction in the number of SNPs required for a cost-effective genome scan. A plausible explanation is that cyclical expansions follow population bottlenecks that establish new disequilibria. Data on more than 1,000 locus pairs indicate that most disequilibria trace to the Neolithic, with no apparent difference between haplotypes that are random or selected through a major disease gene. Short duration may be characteristic of alleles contributing to disease susceptibility and haplotypes characteristic of particular ethnic groups. Alleles that are highly polymorphic in all ethnic groups may be older, neutral, or advantageous, in weak disequilibrium with nearby markers, and therefore less useful for positional cloning of disease genes. Significant disequilibrium at large distance makes the number of suitably chosen SNPs required for genome screening as small as 30,000, or 1 per 100 kb, with greater density (including less common SNPs) reserved for candidate regions.},
bibtype = {article},
author = {Collins, A and Lonjou, C and Morton, N E},
journal = {Proc Natl Acad Sci U S A},
number = {26}
}1998 (3)
A neuronal model of a global workspace in effortful cognitive tasks. Dehaene, S., Kerszberg, M., & Changeux, J. Proc Natl Acad Sci U S A, 95(24):14529–34, 1998.
Paper doi abstract bibtex
Paper doi abstract bibtex A minimal hypothesis is proposed concerning the brain processes underlying effortful tasks. It distinguishes two main computational spaces: a unique global workspace composed of distributed and heavily interconnected neurons with long-range axons, and a set of specialized and modular perceptual, motor, memory, evaluative, and attentional processors. Workspace neurons are mobilized in effortful tasks for which the specialized processors do not suffice. They selectively mobilize or suppress, through descending connections, the contribution of specific processor neurons. In the course of task performance, workspace neurons become spontaneously coactivated, forming discrete though variable spatio-temporal patterns subject to modulation by vigilance signals and to selection by reward signals. A computer simulation of the Stroop task shows workspace activation to increase during acquisition of a novel task, effortful execution, and after errors. We outline predictions for spatio-temporal activation patterns during brain imaging, particularly about the contribution of dorsolateral prefrontal cortex and anterior cingulate to the workspace.
@article{dehaene_neuronal_1998,
title = {A neuronal model of a global workspace in effortful cognitive tasks},
volume = {95},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9826734},
doi = {10/chcbx7},
abstract = {A minimal hypothesis is proposed concerning the brain processes underlying effortful tasks. It distinguishes two main computational spaces: a unique global workspace composed of distributed and heavily interconnected neurons with long-range axons, and a set of specialized and modular perceptual, motor, memory, evaluative, and attentional processors. Workspace neurons are mobilized in effortful tasks for which the specialized processors do not suffice. They selectively mobilize or suppress, through descending connections, the contribution of specific processor neurons. In the course of task performance, workspace neurons become spontaneously coactivated, forming discrete though variable spatio-temporal patterns subject to modulation by vigilance signals and to selection by reward signals. A computer simulation of the Stroop task shows workspace activation to increase during acquisition of a novel task, effortful execution, and after errors. We outline predictions for spatio-temporal activation patterns during brain imaging, particularly about the contribution of dorsolateral prefrontal cortex and anterior cingulate to the workspace.},
number = {24},
journal = {Proc Natl Acad Sci U S A},
author = {Dehaene, S. and Kerszberg, M. and Changeux, J.P.},
year = {1998},
keywords = {\#nosource, *Brain Mapping, *Models, Neurological, *Neural Networks (Computer), Brain/*physiology, Cerebral Cortex/physiology, Cognition/*physiology, Computer Simulation, Humans, Nerve Net/*physiology, Time Factors, Work},
pages = {14529--34},
}Aging and life adjustment after spinal cord injury. Krause, J. S. Spinal Cord, 36(5):320–328, May, 1998. Number: 5
doi abstract bibtex
doi abstract bibtex
STUDY DESIGN: A field study of aging after spinal cord injury (SCI) was conducted by surveying the life adjustment of a large sample of participants with SCI. OBJECTIVES: The purpose of the current study was to compare life adjustment scores between cohorts of participants based on chronologic age, age at injury onset, time since injury and percentage of life with SCI. SUMMARY OF BACKGROUND DATA: Existing cross-sectional research suggests that age is negatively correlated and time since injury is positively correlated with life adjustment. However, few studies had investigated aging among people who have lived 30 or more years with SCI. METHODS: A total of 435 participants, 55 of whom were injured for 30 or more years, completed the Life Situation Questionnaire-Revised (LSQ-R), a measure of multiple SCI outcomes. RESULTS: Results indicated that being injured later in life is associated with a lower overall level of subjective well-being, poorer health, and a less active lifestyle. However, subjective well-being appears to improve throughout the life-cycle, even beyond 30 years post-injury, thus neutralizing the adverse impact of age at onset on subjective well-being, but not on health or activities. CONCLUSIONS: The results suggest that rehabilitation professionals need to pay special attention to problems presented by being injured after the age of 40, particularly as it relates to activities. Living 30 or more years with SCI does not appear to present overwhelming barriers to adjustment.
@article{krause_aging_1998,
title = {Aging and life adjustment after spinal cord injury},
volume = {36},
issn = {1362-4393},
doi = {10.1038/sj.sc.3100540},
abstract = {STUDY DESIGN: A field study of aging after spinal cord injury (SCI) was conducted by surveying the life adjustment of a large sample of participants with SCI.
OBJECTIVES: The purpose of the current study was to compare life adjustment scores between cohorts of participants based on chronologic age, age at injury onset, time since injury and percentage of life with SCI.
SUMMARY OF BACKGROUND DATA: Existing cross-sectional research suggests that age is negatively correlated and time since injury is positively correlated with life adjustment. However, few studies had investigated aging among people who have lived 30 or more years with SCI.
METHODS: A total of 435 participants, 55 of whom were injured for 30 or more years, completed the Life Situation Questionnaire-Revised (LSQ-R), a measure of multiple SCI outcomes.
RESULTS: Results indicated that being injured later in life is associated with a lower overall level of subjective well-being, poorer health, and a less active lifestyle. However, subjective well-being appears to improve throughout the life-cycle, even beyond 30 years post-injury, thus neutralizing the adverse impact of age at onset on subjective well-being, but not on health or activities.
CONCLUSIONS: The results suggest that rehabilitation professionals need to pay special attention to problems presented by being injured after the age of 40, particularly as it relates to activities. Living 30 or more years with SCI does not appear to present overwhelming barriers to adjustment.},
language = {eng},
number = {5},
journal = {Spinal Cord},
author = {Krause, J. S.},
month = may,
year = {1998},
pmid = {9601111},
note = {Number: 5},
keywords = {Adaptation, Psychological, Adult, Aging, Cohort Studies, Health, Humans, Life Style, Longitudinal Studies, Personal Satisfaction, Social Adjustment, Spinal Cord Injuries, Surveys and Questionnaires, Time Factors},
pages = {320--328},
}A mathematical model of the dynamics of scrapie in a sheep flock. Stringer, S. M., Hunter, N., & Woolhouse, M. E. Mathematical biosciences, 153(2):79--98, November, 1998.
abstract bibtex
abstract bibtex
A mathematical model is developed for the dynamics of an outbreak of scrapie in a single sheep flock with the aim of assisting the interpretation of field data. The model incorporates age structure of the sheep population, both horizontal and vertical transmission, genetic predisposition to infection, variable initial load of the infectious agent, and increasing infection load during an incubation period of the same order as sheep life expectancy. This leads to system of partial differential equations with respect to time, age and infection load. Numerical analyses using this model demonstrate that a scrapie outbreak is likely to be of long duration (several decades), will lead to reduction of scrapie susceptible allele frequency (but not to zero), and has different dynamics in homozygous and heterozygous susceptible sheep, even if these genotypes are equally susceptible, due to the different contributions of vertical infection to transmission to genotypes.
@article{stringer_mathematical_1998,
title = {A mathematical model of the dynamics of scrapie in a sheep flock.},
volume = {153},
issn = {0025-5564 0025-5564},
abstract = {A mathematical model is developed for the dynamics of an outbreak of scrapie in a single sheep flock with the aim of assisting the interpretation of field data. The model incorporates age structure of the sheep population, both horizontal and vertical transmission, genetic predisposition to infection, variable initial load of the infectious agent, and increasing infection load during an incubation period of the same order as sheep life expectancy. This leads to system of partial differential equations with respect to time, age and infection load. Numerical analyses using this model demonstrate that a scrapie outbreak is likely to be of long duration (several decades), will lead to reduction of scrapie susceptible allele frequency (but not to zero), and has different dynamics in homozygous and heterozygous susceptible sheep, even if these genotypes are equally susceptible, due to the different contributions of vertical infection to transmission to genotypes.},
language = {eng},
number = {2},
journal = {Mathematical biosciences},
author = {Stringer, S. M. and Hunter, N. and Woolhouse, M. E.},
month = nov,
year = {1998},
pmid = {9825634},
keywords = {*Models, Biological, Age Factors, Alleles, Animals, Birth Rate, Computer Simulation, Disease Outbreaks/*veterinary, Disease Susceptibility, Disease Transmission, Infectious/*veterinary, Female, Incidence, Infectious Disease Transmission, Vertical/*veterinary, Male, Mortality, Prevalence, Scrapie/*epidemiology/genetics/transmission, Sensitivity and Specificity, Sheep, Survival Analysis, Time Factors},
pages = {79--98}
}1996 (2)
Response properties of units in the posterior auditory field deprived of input from the ipsilateral primary auditory cortex. Kitzes, L. & Hollrigel, G. Hear Res, 100(1-2):120-30, 1996. as cited in i̧teNPHeil1998
abstract bibtex
abstract bibtex
The influence of the ipsilateral primary auditory field (AI) on the response properties of neurons in the posterior auditory field (Field P) was examined in three cats anesthetized with sodium pentobarbital. Rate/level functions were obtained, by extracellular recording, from single units in Field P before (n = 38) and after (n = 50) subpial aspiration of AI. The ablations were primarily confined to the medial ectosylvian gyrus, although in one case extended into the high-frequency portion of the anterior auditory field. Comparisons between the behavior of units isolated before and after AI ablation failed to demonstrate any changes in the response properties of neurons in Field P attributable to the ablation. Nonmonotonic response profiles, first spike latency, variability in latency, threshold and maximal discharge rates of the units to acoustic stimuli were not significantly altered by the AI ablation. These results indicate that the basic response properties of neurons in Field P do not depend on input from the ipsilateral AI. This suggests that these properties are most likely determined by thalamic input or by circuitry within Field P.
@Article{Kitzes1996,
author = {LM Kitzes and GS Hollrigel},
journal = {Hear Res},
title = {Response properties of units in the posterior auditory field deprived of input from the ipsilateral primary auditory cortex.},
year = {1996},
note = {as cited in \citeNP{Heil1998}},
number = {1-2},
pages = {120-30},
volume = {100},
abstract = {The influence of the ipsilateral primary auditory field (AI) on the
response properties of neurons in the posterior auditory field (Field
P) was examined in three cats anesthetized with sodium pentobarbital.
Rate/level functions were obtained, by extracellular recording, from
single units in Field P before (n = 38) and after (n = 50) subpial
aspiration of AI. The ablations were primarily confined to the medial
ectosylvian gyrus, although in one case extended into the high-frequency
portion of the anterior auditory field. Comparisons between the behavior
of units isolated before and after AI ablation failed to demonstrate
any changes in the response properties of neurons in Field P attributable
to the ablation. Nonmonotonic response profiles, first spike latency,
variability in latency, threshold and maximal discharge rates of
the units to acoustic stimuli were not significantly altered by the
AI ablation. These results indicate that the basic response properties
of neurons in Field P do not depend on input from the ipsilateral
AI. This suggests that these properties are most likely determined
by thalamic input or by circuitry within Field P.},
keywords = {Computing Methodologies, Human, Language, Learning, Mental Processes, Models, Theoretical, Stochastic Processes, Support, U.S. Gov't, Non-P.H.S., Cognition, Linguistics, Neural Networks (Computer), Practice (Psychology), Non-U.S. Gov't, Memory, Psychological, Task Performance and Analysis, Time Factors, Visual Perception, Adult, Attention, Discrimination Learning, Female, Male, Short-Term, Mental Recall, Orientation, Pattern Recognition, Visual, Perceptual Masking, Reading, Concept Formation, Form Perception, Animals, Corpus Striatum, Shrews, P.H.S., Visual Cortex, Visual Pathways, Acoustic Stimulation, Auditory Cortex, Auditory Perception, Cochlea, Ear, Gerbillinae, Glycine, Hearing, Neurons, Space Perception, Strychnine, Adolescent, Decision Making, Reaction Time, Astrocytoma, Brain Mapping, Brain Neoplasms, Cerebral Cortex, Electric Stimulation, Electrophysiology, Epilepsy, Temporal Lobe, Evoked Potentials, Frontal Lobe, Noise, Parietal Lobe, Scalp, Child, Language Development, Psycholinguistics, Brain, Perception, Speech, Vocalization, Animal, Discrimination (Psychology), Hippocampus, Rats, Calcium, Chelating Agents, Excitatory Postsynaptic Potentials, Glutamic Acid, Guanosine Diphosphate, In Vitro, Neuronal Plasticity, Pyramidal Cells, Receptors, AMPA, Metabotropic Glutamate, N-Methyl-D-Aspartate, Somatosensory Cortex, Synapses, Synaptic Transmission, Thionucleotides, Action Potentials, Calcium Channels, L-Type, Electric Conductivity, Entorhinal Cortex, Neurological, Long-Evans, Infant, Mathematics, Statistics, Probability Learning, Problem Solving, Psychophysics, Association Learning, Child Psychology, Habituation (Psychophysiology), Probability Theory, Analysis of Variance, Semantics, Symbolism, Behavior, Eye Movements, Macaca mulatta, Prefrontal Cortex, Cats, Dogs, Haplorhini, Photic Stimulation, Electroencephalography, Nervous System Physiology, Darkness, Grasshoppers, Light, Membrane Potentials, Neural Inhibition, Afferent, Picrotoxin, Vision, Deoxyglucose, Injections, Microspheres, Neural Pathways, Rhodamines, Choice Behavior, Speech Perception, Verbal Learning, Dominance, Cerebral, Fixation, Ocular, Language Tests, Random Allocation, Comparative Study, Saguinus, Sound Spectrography, Species Specificity, Audiometry, Auditory Threshold, Calibration, Data Interpretation, Statistical, Anesthesia, General, Electrodes, Implanted, Pitch Perception, Sound Localization, Paired-Associate Learning, Serial Learning, Auditory, Age Factors, Motion Perception, Brain Injuries, Computer Simulation, Blindness, Psychomotor Performance, Color Perception, Signal Detection (Psychology), Judgment, ROC Curve, Regression Analysis, 8922986},
}Analysis of Hox gene expression in the chick limb bud. Nelson, C., E., Morgan, B., a., Burke, a., C., Laufer, E., DiMambro, E., Murtaugh, L., C., Gonzales, E., Tessarollo, L., Parada, L., F., & Tabin, C. Development (Cambridge, England), 122(5):1449-66, 5, 1996.
Paper Website abstract bibtex
Paper Website abstract bibtex The vertebrate Hox genes have been shown to be important for patterning the primary and secondary axes of the developing vertebrate embryo. The function of these genes along the primary axis of the embryo has been generally interpreted in the context of positional specification and homeotic transformation of axial structures. The way in which these genes are expressed and function during the development of the secondary axes, particularly the limb, is less clear. In order to provide a reference for understanding the role of the Hox genes in limb patterning, we isolated clones of 23 Hox genes expressed during limb development, characterized their expression patterns and analyzed their regulation by the signalling centers which pattern the limb. The expression patterns of the Abd-B-related Hoxa and Hoxd genes have previously been partially characterized; however, our study reveals that these genes are expressed in patterns more dynamic and complex than generally appreciated, only transiently approximating simple, concentric, nested domains. Detailed analysis of these patterns suggests that the expression of each of the Hoxa and Hoxd genes is regulated in up to three independent phases. Each of these phases appears to be associated with the specification and patterning of one of the proximodistal segments of the limb (upper arm, lower arm and hand). Interestingly, in the last of these phases, the expression of the Hoxd genes violates the general rule of spatial and temporal colinearity of Hox gene expression with gene order along the chromosome. In contrast to the Abd-B-related Hoxa and Hoxd genes, which are expressed in both the fore and hind limbs, different sets of Hoxc genes are expressed in the two limbs. There is a correlation between the relative position of these genes along the chromosome and the axial level of the limb bud in which they are expressed. The more 3' genes are expressed in the fore limb bud while the 5' genes are expressed in the hind limb bud; intermediate genes are transcribed in both limbs. However, there is no clear correlation between the relative position of the genes along the chromosome and their expression domains within the limb. With the exception of Hoxc-11, which is transcribed in a posterior portion of the hind limb, Hoxc gene expression is restricted to the anterior/proximal portion of the limb bud. Importantly, comparison of the distributions of Hoxc-6 RNA and protein products reveals posttranscriptional regulation of this gene, suggesting that caution must be exercised in interpreting the functional significance of the RNA distribution of any of the vertebrate Hox genes. To understand the genesis of the complex patterns of Hox gene expression in the limb bud, we examined the propagation of Hox gene expression relative to cell proliferation. We find that shifts in Hox gene expression cannot be attributed to passive expansion due to cell proliferation. Rather, phase-specific Hox gene expression patterns appear to result from a context-dependent response of the limb mesoderm to Sonic hedgehog. Sonic hedgehog (the patterning signal from the Zone of Polarizing Activity) is known to be able to activate Hoxd gene expression in the limb. Although we find that Sonic hedgehog is capable of initiating and polarizing Hoxd gene expression during both of the latter two phases of Hox gene expression, the specific patterns induced are not determined by the signal, but depend upon the temporal context of the mesoderm receiving the signal. Misexpression of Sonic hedgehog also reveals that Hoxb-9, which is normally excluded from the posterior mesenchyme of the leg, is negatively regulated by Sonic hedgehog and that Hoxc-11, which is expressed in the posterior portion of the leg, is not affected by Sonic hedgehog and hence is not required to pattern the skeletal elements of the lower leg.
@article{
title = {Analysis of Hox gene expression in the chick limb bud.},
type = {article},
year = {1996},
identifiers = {[object Object]},
keywords = {Amino Acid Sequence,Animals,Base Sequence,Cell Movement,Chick Embryo,Extremities,Extremities: embryology,Gene Expression Regulation, Developmental,Gene Library,Genes, Homeobox,Hedgehog Proteins,Immunohistochemistry,In Situ Hybridization,Models, Genetic,Molecular Sequence Data,Morphogenesis,Muscles,Muscles: cytology,Muscles: embryology,Polymerase Chain Reaction,Proteins,Proteins: metabolism,Time Factors,Tissue Distribution,Trans-Activators,Transcription, Genetic},
pages = {1449-66},
volume = {122},
websites = {http://www.ncbi.nlm.nih.gov/pubmed/8625833},
month = {5},
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abstract = {The vertebrate Hox genes have been shown to be important for patterning the primary and secondary axes of the developing vertebrate embryo. The function of these genes along the primary axis of the embryo has been generally interpreted in the context of positional specification and homeotic transformation of axial structures. The way in which these genes are expressed and function during the development of the secondary axes, particularly the limb, is less clear. In order to provide a reference for understanding the role of the Hox genes in limb patterning, we isolated clones of 23 Hox genes expressed during limb development, characterized their expression patterns and analyzed their regulation by the signalling centers which pattern the limb. The expression patterns of the Abd-B-related Hoxa and Hoxd genes have previously been partially characterized; however, our study reveals that these genes are expressed in patterns more dynamic and complex than generally appreciated, only transiently approximating simple, concentric, nested domains. Detailed analysis of these patterns suggests that the expression of each of the Hoxa and Hoxd genes is regulated in up to three independent phases. Each of these phases appears to be associated with the specification and patterning of one of the proximodistal segments of the limb (upper arm, lower arm and hand). Interestingly, in the last of these phases, the expression of the Hoxd genes violates the general rule of spatial and temporal colinearity of Hox gene expression with gene order along the chromosome. In contrast to the Abd-B-related Hoxa and Hoxd genes, which are expressed in both the fore and hind limbs, different sets of Hoxc genes are expressed in the two limbs. There is a correlation between the relative position of these genes along the chromosome and the axial level of the limb bud in which they are expressed. The more 3' genes are expressed in the fore limb bud while the 5' genes are expressed in the hind limb bud; intermediate genes are transcribed in both limbs. However, there is no clear correlation between the relative position of the genes along the chromosome and their expression domains within the limb. With the exception of Hoxc-11, which is transcribed in a posterior portion of the hind limb, Hoxc gene expression is restricted to the anterior/proximal portion of the limb bud. Importantly, comparison of the distributions of Hoxc-6 RNA and protein products reveals posttranscriptional regulation of this gene, suggesting that caution must be exercised in interpreting the functional significance of the RNA distribution of any of the vertebrate Hox genes. To understand the genesis of the complex patterns of Hox gene expression in the limb bud, we examined the propagation of Hox gene expression relative to cell proliferation. We find that shifts in Hox gene expression cannot be attributed to passive expansion due to cell proliferation. Rather, phase-specific Hox gene expression patterns appear to result from a context-dependent response of the limb mesoderm to Sonic hedgehog. Sonic hedgehog (the patterning signal from the Zone of Polarizing Activity) is known to be able to activate Hoxd gene expression in the limb. Although we find that Sonic hedgehog is capable of initiating and polarizing Hoxd gene expression during both of the latter two phases of Hox gene expression, the specific patterns induced are not determined by the signal, but depend upon the temporal context of the mesoderm receiving the signal. Misexpression of Sonic hedgehog also reveals that Hoxb-9, which is normally excluded from the posterior mesenchyme of the leg, is negatively regulated by Sonic hedgehog and that Hoxc-11, which is expressed in the posterior portion of the leg, is not affected by Sonic hedgehog and hence is not required to pattern the skeletal elements of the lower leg.},
bibtype = {article},
author = {Nelson, C E and Morgan, B a and Burke, a C and Laufer, E and DiMambro, E and Murtaugh, L C and Gonzales, E and Tessarollo, L and Parada, L F and Tabin, C},
journal = {Development (Cambridge, England)},
number = {5}
}1995 (1)
Spatial repetition blindness is modulated by selective attention to color or shape. Kanwisher, N, Driver, J, & Machado, L Cognit Psychol, 29(3):303-37, 1995.
abstract bibtex
abstract bibtex
Subjects reported either the colors or shapes of two simultaneous masked letters. Our first study found that they were less accurate when the reported features were identical ("repetition blindness," or RB), while repetition along the unreported dimension had no effect. Three follow-up studies confirmed that when the same dimension was judged (overtly or covertly) for both stimuli, performance was only affected by repetition along that dimension. However, when different dimensions were judged for the two stimuli, performance was affected by repetition on both dimensions. These findings support new conclusions about both RB and visual attention. First, RB depends critically on visual attention, rather than simply on the stimulus presented or the overt response required. Second, while attention can be restricted to a single visual dimension, this is efficient only when the same dimension is selected for both objects. Selecting the color of one object and the shape of another simultaneous object results in both dimensions being accessed for both objects.
@Article{Kanwisher1995,
author = {N Kanwisher and J Driver and L Machado},
journal = {Cognit Psychol},
title = {Spatial repetition blindness is modulated by selective attention to color or shape.},
year = {1995},
number = {3},
pages = {303-37},
volume = {29},
abstract = {Subjects reported either the colors or shapes of two simultaneous
masked letters. Our first study found that they were less accurate
when the reported features were identical ("repetition blindness,"
or RB), while repetition along the unreported dimension had no effect.
Three follow-up studies confirmed that when the same dimension was
judged (overtly or covertly) for both stimuli, performance was only
affected by repetition along that dimension. However, when different
dimensions were judged for the two stimuli, performance was affected
by repetition on both dimensions. These findings support new conclusions
about both RB and visual attention. First, RB depends critically
on visual attention, rather than simply on the stimulus presented
or the overt response required. Second, while attention can be restricted
to a single visual dimension, this is efficient only when the same
dimension is selected for both objects. Selecting the color of one
object and the shape of another simultaneous object results in both
dimensions being accessed for both objects.},
keywords = {Computing Methodologies, Human, Language, Learning, Mental Processes, Models, Theoretical, Stochastic Processes, Support, U.S. Gov't, Non-P.H.S., Cognition, Linguistics, Neural Networks (Computer), Practice (Psychology), Non-U.S. Gov't, Memory, Psychological, Task Performance and Analysis, Time Factors, Visual Perception, Adult, Attention, Discrimination Learning, Female, Male, Short-Term, Mental Recall, Orientation, Pattern Recognition, Visual, Perceptual Masking, Reading, Concept Formation, Form Perception, Animals, Corpus Striatum, Shrews, P.H.S., Visual Cortex, Visual Pathways, Acoustic Stimulation, Auditory Cortex, Auditory Perception, Cochlea, Ear, Gerbillinae, Glycine, Hearing, Neurons, Space Perception, Strychnine, Adolescent, Decision Making, Reaction Time, Astrocytoma, Brain Mapping, Brain Neoplasms, Cerebral Cortex, Electric Stimulation, Electrophysiology, Epilepsy, Temporal Lobe, Evoked Potentials, Frontal Lobe, Noise, Parietal Lobe, Scalp, Child, Language Development, Psycholinguistics, Brain, Perception, Speech, Vocalization, Animal, Discrimination (Psychology), Hippocampus, Rats, Calcium, Chelating Agents, Excitatory Postsynaptic Potentials, Glutamic Acid, Guanosine Diphosphate, In Vitro, Neuronal Plasticity, Pyramidal Cells, Receptors, AMPA, Metabotropic Glutamate, N-Methyl-D-Aspartate, Somatosensory Cortex, Synapses, Synaptic Transmission, Thionucleotides, Action Potentials, Calcium Channels, L-Type, Electric Conductivity, Entorhinal Cortex, Neurological, Long-Evans, Infant, Mathematics, Statistics, Probability Learning, Problem Solving, Psychophysics, Association Learning, Child Psychology, Habituation (Psychophysiology), Probability Theory, Analysis of Variance, Semantics, Symbolism, Behavior, Eye Movements, Macaca mulatta, Prefrontal Cortex, Cats, Dogs, Haplorhini, Photic Stimulation, Electroencephalography, Nervous System Physiology, Darkness, Grasshoppers, Light, Membrane Potentials, Neural Inhibition, Afferent, Picrotoxin, Vision, Deoxyglucose, Injections, Microspheres, Neural Pathways, Rhodamines, Choice Behavior, Speech Perception, Verbal Learning, Dominance, Cerebral, Fixation, Ocular, Language Tests, Random Allocation, Comparative Study, Saguinus, Sound Spectrography, Species Specificity, Audiometry, Auditory Threshold, Calibration, Data Interpretation, Statistical, Anesthesia, General, Electrodes, Implanted, Pitch Perception, Sound Localization, Paired-Associate Learning, Serial Learning, Auditory, Age Factors, Motion Perception, Brain Injuries, Computer Simulation, Blindness, Psychomotor Performance, Color Perception, 8556848},
}1994 (1)
Repetition blindness between visually different items: The case of pictures and words. Bavelier, D Cognition, 51(3):199-236, 1994.
abstract bibtex
abstract bibtex
Repetition blindness (RB) is the failure to see or recall the second of two visually similar or identical items in rapid serial visual presentation. It was initially demonstrated by Kanwisher (1987), who proposed that a second token of a given word or object type cannot be established when the two items occur close in time. Bavelier and Potter (1992) showed that RB also occurs between visually different items that are phonologically similar. They proposed that RB may occur not only when the targets are physically similar, but also when they have to be registered or encoded in short-term memory (STM) along dimensions on which they are similar. This hypothesis predicts that RB between visually different items should not be restricted to words, but should occur with any stimuli, as long as the task requires these stimuli to be encoded along dimensions on which they are similar. Moreover, it also implies that a task that changes the preferred code of targets will affect the size of RB. The first prediction was confirmed by establishing RB between phonologically similar pictures and words, whether semantically related (the picture of a cat and the word "cat") or not (the picture of a sun and the word "son"), when using a task that requires phonological encoding (Experiments 1 and 2). The second prediction was also supported: the magnitude of RB depended on whether the task required similar or different codes for pictures and words (Experiments 3 and 4). These experiments confirm that RB between visually different items is due to the similarity of the codes initially used in STM. The results suggest that RB can occur at any step during the instantiation of a token, arising not only from a failure to create a new token, but also from a failure to stabilize an opened token. In this view, tokens are to be seen as dynamical entities, built over time as a function of type activation and task requirements, and varying in stability as a function of the information that is entered into them.
@Article{Bavelier1994,
author = {D Bavelier},
journal = {Cognition},
title = {Repetition blindness between visually different items: {T}he case of pictures and words.},
year = {1994},
number = {3},
pages = {199-236},
volume = {51},
abstract = {Repetition blindness (RB) is the failure to see or recall the second
of two visually similar or identical items in rapid serial visual
presentation. It was initially demonstrated by Kanwisher (1987),
who proposed that a second token of a given word or object type cannot
be established when the two items occur close in time. Bavelier and
Potter (1992) showed that RB also occurs between visually different
items that are phonologically similar. They proposed that RB may
occur not only when the targets are physically similar, but also
when they have to be registered or encoded in short-term memory (STM)
along dimensions on which they are similar. This hypothesis predicts
that RB between visually different items should not be restricted
to words, but should occur with any stimuli, as long as the task
requires these stimuli to be encoded along dimensions on which they
are similar. Moreover, it also implies that a task that changes the
preferred code of targets will affect the size of RB. The first prediction
was confirmed by establishing RB between phonologically similar pictures
and words, whether semantically related (the picture of a cat and
the word "cat") or not (the picture of a sun and the word "son"),
when using a task that requires phonological encoding (Experiments
1 and 2). The second prediction was also supported: the magnitude
of RB depended on whether the task required similar or different
codes for pictures and words (Experiments 3 and 4). These experiments
confirm that RB between visually different items is due to the similarity
of the codes initially used in STM. The results suggest that RB can
occur at any step during the instantiation of a token, arising not
only from a failure to create a new token, but also from a failure
to stabilize an opened token. In this view, tokens are to be seen
as dynamical entities, built over time as a function of type activation
and task requirements, and varying in stability as a function of
the information that is entered into them.},
keywords = {Computing Methodologies, Human, Language, Learning, Mental Processes, Models, Theoretical, Stochastic Processes, Support, U.S. Gov't, Non-P.H.S., Cognition, Linguistics, Neural Networks (Computer), Practice (Psychology), Non-U.S. Gov't, Memory, Psychological, Task Performance and Analysis, Time Factors, Visual Perception, Adult, Attention, Discrimination Learning, Female, Male, Short-Term, Mental Recall, Orientation, Pattern Recognition, Visual, Perceptual Masking, Reading, 8194301},
}1989 (1)
Modified formalin test: characteristic biphasic pain response. Shibata, M., Ohkubo, T., Takahashi, H., & Inoki, R. Pain, 38(3):347–352, September, 1989. PMID 2478947
doi bibtex
doi bibtex
1986 (1)
Congenital adrenal hyperplasia: long-term results following vaginal reconstruction. Azziz, R, Mulaikal, R M, Migeon, C J, Jones, J., & Rock, J A Fertility and sterility, 46(6):1011–1014, December, 1986.
bibtex
bibtex
1985 (1)
Responses of single neurones in cat auditory cortex to time-varying stimuli: Frequency-modulated tones of narrow excursion. Phillips, D., Mendelson, J., Cynader, M., & Douglas, R. Exp Brain Res, 58(3):443-54, 1985.
abstract bibtex
abstract bibtex
In the primary auditory cortex of cats anaesthetized with nitrous oxide, single neurones were examined with respect to their responses to tone bursts and linear modulations of the frequency of an on-going continuous tone. Using FM ramps of 2.0 kHz excursion and varying centre frequency, each of 39 neurones was examined for its preference for the direction of frequency change of a ramp whose centre frequency was varied in and around the neurone's response area. Direction preference was strictly associated with the slopes of the cell's spike count-versus-frequency function over the frequency range covered by the ramp. Preferences for upward- and downward-directed ramps were associated with the low- and high-frequency slopes of the spike count function, respectively. The strength of the cell's direction preference was associated with the relative steepness of the spike count function over the frequency range covered by the ramp. The timing of discharges elicited by the frequency modulations was found to be the sum of the cell's latent period for tone bursts plus the time after ramp onset that the stimulus frequency fell within the neurone's response area. The implications of these data for the processing of narrow and broad frequency-modulated ramps are discussed.
@Article{Phillips1985,
author = {DP Phillips and JR Mendelson and MS Cynader and RM Douglas},
journal = {Exp Brain Res},
title = {Responses of single neurones in cat auditory cortex to time-varying stimuli: {F}requency-modulated tones of narrow excursion.},
year = {1985},
number = {3},
pages = {443-54},
volume = {58},
abstract = {In the primary auditory cortex of cats anaesthetized with nitrous
oxide, single neurones were examined with respect to their responses
to tone bursts and linear modulations of the frequency of an on-going
continuous tone. Using FM ramps of 2.0 kHz excursion and varying
centre frequency, each of 39 neurones was examined for its preference
for the direction of frequency change of a ramp whose centre frequency
was varied in and around the neurone's response area. Direction preference
was strictly associated with the slopes of the cell's spike count-versus-frequency
function over the frequency range covered by the ramp. Preferences
for upward- and downward-directed ramps were associated with the
low- and high-frequency slopes of the spike count function, respectively.
The strength of the cell's direction preference was associated with
the relative steepness of the spike count function over the frequency
range covered by the ramp. The timing of discharges elicited by the
frequency modulations was found to be the sum of the cell's latent
period for tone bursts plus the time after ramp onset that the stimulus
frequency fell within the neurone's response area. The implications
of these data for the processing of narrow and broad frequency-modulated
ramps are discussed.},
keywords = {Computing Methodologies, Human, Language, Learning, Mental Processes, Models, Theoretical, Stochastic Processes, Support, U.S. Gov't, Non-P.H.S., Cognition, Linguistics, Neural Networks (Computer), Practice (Psychology), Non-U.S. Gov't, Memory, Psychological, Task Performance and Analysis, Time Factors, Visual Perception, Adult, Attention, Discrimination Learning, Female, Male, Short-Term, Mental Recall, Orientation, Pattern Recognition, Visual, Perceptual Masking, Reading, Concept Formation, Form Perception, Animals, Corpus Striatum, Shrews, P.H.S., Visual Cortex, Visual Pathways, Acoustic Stimulation, Auditory Cortex, Auditory Perception, Cochlea, Ear, Gerbillinae, Glycine, Hearing, Neurons, Space Perception, Strychnine, Adolescent, Decision Making, Reaction Time, Astrocytoma, Brain Mapping, Brain Neoplasms, Cerebral Cortex, Electric Stimulation, Electrophysiology, Epilepsy, Temporal Lobe, Evoked Potentials, Frontal Lobe, Noise, Parietal Lobe, Scalp, Child, Language Development, Psycholinguistics, Brain, Perception, Speech, Vocalization, Animal, Discrimination (Psychology), Hippocampus, Rats, Calcium, Chelating Agents, Excitatory Postsynaptic Potentials, Glutamic Acid, Guanosine Diphosphate, In Vitro, Neuronal Plasticity, Pyramidal Cells, Receptors, AMPA, Metabotropic Glutamate, N-Methyl-D-Aspartate, Somatosensory Cortex, Synapses, Synaptic Transmission, Thionucleotides, Action Potentials, Calcium Channels, L-Type, Electric Conductivity, Entorhinal Cortex, Neurological, Long-Evans, Infant, Mathematics, Statistics, Probability Learning, Problem Solving, Psychophysics, Association Learning, Child Psychology, Habituation (Psychophysiology), Probability Theory, Analysis of Variance, Semantics, Symbolism, Behavior, Eye Movements, Macaca mulatta, Prefrontal Cortex, Cats, Dogs, Haplorhini, Photic Stimulation, Electroencephalography, Nervous System Physiology, Darkness, Grasshoppers, Light, Membrane Potentials, Neural Inhibition, Afferent, Picrotoxin, Vision, Deoxyglucose, Injections, Microspheres, Neural Pathways, Rhodamines, Choice Behavior, Speech Perception, Verbal Learning, Dominance, Cerebral, Fixation, Ocular, Language Tests, Random Allocation, Comparative Study, Saguinus, Sound Spectrography, Species Specificity, Audiometry, Auditory Threshold, Calibration, Data Interpretation, Statistical, Anesthesia, General, Electrodes, Implanted, Pitch Perception, Sound Localization, Paired-Associate Learning, Serial Learning, Auditory, Age Factors, Motion Perception, Brain Injuries, Computer Simulation, Blindness, Psychomotor Performance, Color Perception, Signal Detection (Psychology), Judgment, ROC Curve, Regression Analysis, Music, Probability, Arm, Cerebrovascular Disorders, Hemiplegia, Movement, Muscle, Skeletal, Myoclonus, Robotics, Magnetoencephalography, Phonetics, Software, Speech Production Measurement, Epilepsies, Partial, Laterality, Stereotaxic Techniques, Germany, Speech Acoustics, Verbal Behavior, Child Development, Instinct, Brain Stem, Coma, Diagnosis, Differential, Hearing Disorders, Hearing Loss, Central, Neuroma, Acoustic, Dendrites, Down-Regulation, Patch-Clamp Techniques, Wistar, Up-Regulation, Aged, Aphasia, Middle Aged, Cones (Retina), Primates, Retina, Retinal Ganglion Cells, Tympanic Membrane, Cell Communication, Extremities, Biological, Motor Activity, Rana catesbeiana, Spinal Cord, Central Nervous System, Motion, Motor Cortex, Intelligence, Macaca fascicularis, Adoption, Critical Period (Psychology), France, Korea, Magnetic Resonance Imaging, Multilingualism, Auditory Pathways, Cochlear Nerve, Loudness Perception, Neural Conduction, 4007088},
}1984 (1)
Responses of single neurons in posterior field of cat auditory cortex to tonal stimulation. Phillips, D. & Orman, S. J Neurophysiol, 51(1):147-63, 1984. as cited by i̧teNPHeil1998
abstract bibtex
abstract bibtex
In the auditory cortex of barbiturate-anesthetized cats, the posterior auditory field (field P) was identified by its tonotopic organization, and single neurons in that field were studied quantitatively for their sensitivity to the frequency and intensity of tonal stimuli presented via calibrated, sealed stimulating systems. Field P neurons had narrow, V-shaped, threshold frequency tuning curves. At suprathreshold levels, spike counts were generally greatest at frequencies at or close to the neuron's threshold best frequency (BF). Eighty-six percent of posterior-field neurons displayed spike counts that were a nonmonotonic function of the intensity of a BF tone. Of these, over 90% showed at least a 50% reduction in spike count at high stimulus levels, and almost 20% of nonmonotonic cells ceased responding entirely at high stimulus intensities. The nonmonotonic shape of spike count-versus-intensity profiles was typically preserved across the range of frequencies to which any given neuron was responsive. For some neurons, this had the consequence of generating a completely circumscribed frequency-intensity response area. That is, these neurons responded to a tonal stimulus only if the stimulus was within a restricted range of both frequency and intensity. These response areas showed internal organizations that appeared to reflect one or both of two processes. For some neurons, the optimal sound pressure level for spike counts varied with tone frequency, roughly paralleling the threshold tuning curve. For other neurons, the optimal sound pressure level tended to be constant across frequency despite threshold variations of up to 20 dB. The minimum response latencies of posterior-field neurons were generally in the range of 20-50 ms, while cells in the primary auditory cortex (AI) in the same animals generally had minimum latent periods of less than 20 ms. Comparison of these data with those previously presented for neurons in two other cortical auditory fields suggests that the cat's auditory cortex might show an interfield segregation of neurons according to their coding properties.
@Article{Phillips1984,
author = {DP Phillips and SS Orman},
journal = {J Neurophysiol},
title = {Responses of single neurons in posterior field of cat auditory cortex to tonal stimulation.},
year = {1984},
note = {as cited by \citeNP{Heil1998}},
number = {1},
pages = {147-63},
volume = {51},
abstract = {In the auditory cortex of barbiturate-anesthetized cats, the posterior
auditory field (field P) was identified by its tonotopic organization,
and single neurons in that field were studied quantitatively for
their sensitivity to the frequency and intensity of tonal stimuli
presented via calibrated, sealed stimulating systems. Field P neurons
had narrow, V-shaped, threshold frequency tuning curves. At suprathreshold
levels, spike counts were generally greatest at frequencies at or
close to the neuron's threshold best frequency (BF). Eighty-six percent
of posterior-field neurons displayed spike counts that were a nonmonotonic
function of the intensity of a BF tone. Of these, over 90\% showed
at least a 50\% reduction in spike count at high stimulus levels,
and almost 20\% of nonmonotonic cells ceased responding entirely
at high stimulus intensities. The nonmonotonic shape of spike count-versus-intensity
profiles was typically preserved across the range of frequencies
to which any given neuron was responsive. For some neurons, this
had the consequence of generating a completely circumscribed frequency-intensity
response area. That is, these neurons responded to a tonal stimulus
only if the stimulus was within a restricted range of both frequency
and intensity. These response areas showed internal organizations
that appeared to reflect one or both of two processes. For some neurons,
the optimal sound pressure level for spike counts varied with tone
frequency, roughly paralleling the threshold tuning curve. For other
neurons, the optimal sound pressure level tended to be constant across
frequency despite threshold variations of up to 20 dB. The minimum
response latencies of posterior-field neurons were generally in the
range of 20-50 ms, while cells in the primary auditory cortex (AI)
in the same animals generally had minimum latent periods of less
than 20 ms. Comparison of these data with those previously presented
for neurons in two other cortical auditory fields suggests that the
cat's auditory cortex might show an interfield segregation of neurons
according to their coding properties.},
keywords = {Computing Methodologies, Human, Language, Learning, Mental Processes, Models, Theoretical, Stochastic Processes, Support, U.S. Gov't, Non-P.H.S., Cognition, Linguistics, Neural Networks (Computer), Practice (Psychology), Non-U.S. Gov't, Memory, Psychological, Task Performance and Analysis, Time Factors, Visual Perception, Adult, Attention, Discrimination Learning, Female, Male, Short-Term, Mental Recall, Orientation, Pattern Recognition, Visual, Perceptual Masking, Reading, Concept Formation, Form Perception, Animals, Corpus Striatum, Shrews, P.H.S., Visual Cortex, Visual Pathways, Acoustic Stimulation, Auditory Cortex, Auditory Perception, Cochlea, Ear, Gerbillinae, Glycine, Hearing, Neurons, Space Perception, Strychnine, Adolescent, Decision Making, Reaction Time, Astrocytoma, Brain Mapping, Brain Neoplasms, Cerebral Cortex, Electric Stimulation, Electrophysiology, Epilepsy, Temporal Lobe, Evoked Potentials, Frontal Lobe, Noise, Parietal Lobe, Scalp, Child, Language Development, Psycholinguistics, Brain, Perception, Speech, Vocalization, Animal, Discrimination (Psychology), Hippocampus, Rats, Calcium, Chelating Agents, Excitatory Postsynaptic Potentials, Glutamic Acid, Guanosine Diphosphate, In Vitro, Neuronal Plasticity, Pyramidal Cells, Receptors, AMPA, Metabotropic Glutamate, N-Methyl-D-Aspartate, Somatosensory Cortex, Synapses, Synaptic Transmission, Thionucleotides, Action Potentials, Calcium Channels, L-Type, Electric Conductivity, Entorhinal Cortex, Neurological, Long-Evans, Infant, Mathematics, Statistics, Probability Learning, Problem Solving, Psychophysics, Association Learning, Child Psychology, Habituation (Psychophysiology), Probability Theory, Analysis of Variance, Semantics, Symbolism, Behavior, Eye Movements, Macaca mulatta, Prefrontal Cortex, Cats, Dogs, Haplorhini, Photic Stimulation, Electroencephalography, Nervous System Physiology, Darkness, Grasshoppers, Light, Membrane Potentials, Neural Inhibition, Afferent, Picrotoxin, Vision, Deoxyglucose, Injections, Microspheres, Neural Pathways, Rhodamines, Choice Behavior, Speech Perception, Verbal Learning, Dominance, Cerebral, Fixation, Ocular, Language Tests, Random Allocation, Comparative Study, Saguinus, Sound Spectrography, Species Specificity, Audiometry, Auditory Threshold, Calibration, Data Interpretation, Statistical, Anesthesia, General, Electrodes, Implanted, Pitch Perception, Sound Localization, Paired-Associate Learning, Serial Learning, Auditory, Age Factors, Motion Perception, Brain Injuries, Computer Simulation, Blindness, Psychomotor Performance, Color Perception, Signal Detection (Psychology), Judgment, ROC Curve, Regression Analysis, Music, Probability, Arm, Cerebrovascular Disorders, Hemiplegia, Movement, Muscle, Skeletal, Myoclonus, Robotics, Magnetoencephalography, Phonetics, Software, Speech Production Measurement, Epilepsies, Partial, Laterality, Stereotaxic Techniques, Germany, Speech Acoustics, Verbal Behavior, Child Development, Instinct, Brain Stem, Coma, Diagnosis, Differential, Hearing Disorders, Hearing Loss, Central, Neuroma, Acoustic, Dendrites, Down-Regulation, Patch-Clamp Techniques, Wistar, Up-Regulation, Aged, Aphasia, Middle Aged, Cones (Retina), Primates, Retina, Retinal Ganglion Cells, Tympanic Membrane, Cell Communication, Extremities, Biological, Motor Activity, Rana catesbeiana, Spinal Cord, Central Nervous System, Motion, Motor Cortex, Intelligence, Macaca fascicularis, Adoption, Critical Period (Psychology), France, Korea, Magnetic Resonance Imaging, Multilingualism, Auditory Pathways, Cochlear Nerve, Loudness Perception, 6693932},
}1980 (1)
Effect of azelaic acid on human malignant melanoma. Nazzaro-Porro, M, Passi, S, Zina, G, Bernengo, A, Breathnach, A, Gallagher, S, & Morpurgo, G Lancet, 1(8178):1109–1111, May, 1980.
Paper abstract bibtex
Paper abstract bibtex In 23 patients with malignant melanoma, including some with metastases and terminal patients, topical and oral (10–15 g daily) azelaic acid given for 1–12 weeks before surgical excision of the lesions was followed by arrest and subsequent regression of the advancing edge of lesions, reduction in size and flattening of nodular areas, and progressive lightening of pigmentation. Histological and ultrastructural effects included: degeneration and disappearance of malignant epidermal and dermal melanocytes with reduction of junctional activity; epidermal proliferation and return towards normal organisation; reappearance of papillary dermis, pilosebaceous units, and sweat glands; separation of dermal melanoma tumour masses into smaller collections of cells by regenerating connective tissue; and increase in number of dermal mast cells, macrophages, and round cells. These preliminary results indicate a direct cytotoxic effect of azelaic acid on melanocytes of human melanoma.
@article{nazzaro-porro_effect_1980,
title = {Effect of azelaic acid on human malignant melanoma},
volume = {1},
issn = {0140-6736},
url = {http://www.ncbi.nlm.nih.gov/pubmed/6103442},
abstract = {In 23 patients with malignant melanoma, including some with metastases and terminal patients, topical and oral (10--15 g daily) azelaic acid given for 1--12 weeks before surgical excision of the lesions was followed by arrest and subsequent regression of the advancing edge of lesions, reduction in size and flattening of nodular areas, and progressive lightening of pigmentation. Histological and ultrastructural effects included: degeneration and disappearance of malignant epidermal and dermal melanocytes with reduction of junctional activity; epidermal proliferation and return towards normal organisation; reappearance of papillary dermis, pilosebaceous units, and sweat glands; separation of dermal melanoma tumour masses into smaller collections of cells by regenerating connective tissue; and increase in number of dermal mast cells, macrophages, and round cells. These preliminary results indicate a direct cytotoxic effect of azelaic acid on melanocytes of human melanoma.},
number = {8178},
urldate = {2012-07-19},
journal = {Lancet},
author = {Nazzaro-Porro, M and Passi, S and Zina, G and Bernengo, A and Breathnach, A and Gallagher, S and Morpurgo, G},
month = may,
year = {1980},
pmid = {6103442},
keywords = {Administration, Oral, Administration, Topical, Dicarboxylic Acids, Follow-Up Studies, Humans, Melanoma, Microscopy, Electron, Postoperative Care, Preoperative Care, Skin Neoplasms, Time Factors},
pages = {1109--1111},
}1979 (1)
Recognition and management of children with increased lead absorption. Chisolm, J J & Barltrop, D Archives of Disease in Childhood, 54(4):249–262, April, 1979.
Paper bibtex
Paper bibtex @article{chisolm_recognition_1979,
title = {Recognition and management of children with increased lead absorption},
volume = {54},
issn = {1468-2044},
url = {http://www.ncbi.nlm.nih.gov/pubmed/110270},
number = {4},
urldate = {2010-10-12},
journal = {Archives of Disease in Childhood},
author = {Chisolm, J J and Barltrop, D},
month = apr,
year = {1979},
pmid = {110270},
keywords = {Absorption, Acute Disease, Behavior, Bone Marrow, Bone and Bones, Brain Diseases, Child, Dimercaprol, Edetic Acid, Heme, Humans, Kidney, Lead, Lead Poisoning, Time Factors},
pages = {249--262},
}1975 (1)
Water metabolism in the llama. Rübsamen, K & Engelhardt, W V Comparative biochemistry and physiology. A, Comparative physiology, 52(4):595--598, December, 1975. 00013 PMID: 1179
bibtex
bibtex
@article{rubsamen_water_1975,
title = {Water metabolism in the llama},
volume = {52},
issn = {0300-9629},
language = {eng},
number = {4},
journal = {Comparative biochemistry and physiology. A, Comparative physiology},
author = {Rübsamen, K and Engelhardt, W V},
month = dec,
year = {1975},
note = {00013 PMID: 1179},
keywords = {Animals, Artiodactyla, Body Water, Body Weight, Camelids, New World, Diet, Female, Goats, Male, Species Specificity, Time Factors, Water, Water Deprivation},
pages = {595--598}
}undefined (2)
Gamma-band activity reflects multisensory matching in working memory. Senkowski, D., Schneider, T. R., Tandler, F., & Engel, A. K. 198(2):363--372. 00016 PMID: 19458939
doi abstract bibtex
doi abstract bibtex
In real-world situations, the integration of sensory information in working memory (WM) is an important mechanism for the recognition of objects. Studies in single sensory modalities show that object recognition is facilitated if bottom-up inputs match a template held in WM, and that this effect may be linked to enhanced synchronization of neurons in the gamma-band (\textgreater30 Hz). Natural objects, however, frequently provide inputs to multiple sensory modalities. In this EEG study, we examined the integration of semantically matching or non-matching visual and auditory inputs using a delayed visual-to-auditory object-matching paradigm. In the event-related potentials (ERPs) triggered by auditory inputs, effects of semantic matching were observed after 120-170 ms at frontal and posterior regions, indicating WM-specific processing across modalities, and after 250-400 ms over medial-central regions, possibly reflecting the contextual integration of sensory inputs. Additionally, total gamma-band activity (GBA) with medial-central topography after 120-180 ms was larger for matching compared to non-matching trials. This demonstrates that multisensory matching in WM is reflected by GBA and that dynamic coupling of neural populations in this frequency range might be a crucial mechanism for integrative multisensory processes.
@article{ senkowski_gamma-band_2009,
title = {Gamma-band activity reflects multisensory matching in working memory},
volume = {198},
issn = {1432-1106},
doi = {10.1007/s00221-009-1835-0},
abstract = {In real-world situations, the integration of sensory information in working memory ({WM}) is an important mechanism for the recognition of objects. Studies in single sensory modalities show that object recognition is facilitated if bottom-up inputs match a template held in {WM}, and that this effect may be linked to enhanced synchronization of neurons in the gamma-band ({\textgreater}30 Hz). Natural objects, however, frequently provide inputs to multiple sensory modalities. In this {EEG} study, we examined the integration of semantically matching or non-matching visual and auditory inputs using a delayed visual-to-auditory object-matching paradigm. In the event-related potentials ({ERPs}) triggered by auditory inputs, effects of semantic matching were observed after 120-170 ms at frontal and posterior regions, indicating {WM}-specific processing across modalities, and after 250-400 ms over medial-central regions, possibly reflecting the contextual integration of sensory inputs. Additionally, total gamma-band activity ({GBA}) with medial-central topography after 120-180 ms was larger for matching compared to non-matching trials. This demonstrates that multisensory matching in {WM} is reflected by {GBA} and that dynamic coupling of neural populations in this frequency range might be a crucial mechanism for integrative multisensory processes.},
pages = {363--372},
number = {2},
journaltitle = {Experimental Brain Research},
shortjournal = {Exp Brain Res},
author = {Senkowski, Daniel and Schneider, Till R. and Tandler, Frithjof and Engel, Andreas K.},
date = {2009-09},
note = {00016 {PMID}: 19458939},
keywords = {Acoustic Stimulation, Adult, Analysis of Variance, Auditory Perception, brain, Brain mapping, electroencephalography, Evoked Potentials, Female, Humans, Male, Memory, Short-Term, Neuropsychological Tests, Photic Stimulation, Reaction Time, Time Factors, Visual Perception, Young Adult},
file = {Senkowski et al_2009_Experimental Brain Research_Gamma-band activity reflects multisensory matching in working memory.pdf:files/1296/Senkowski et al_2009_Experimental Brain Research_Gamma-band activity reflects multisensory matching in working memory.pdf:application/pdf}
}Risk factors for symptomatic knee osteoarthritis fifteen to twenty-two years after meniscectomy. Englund, M. & Lohmander, L. S. 50(9):2811--2819.
doi abstract bibtex
doi abstract bibtex
OBJECTIVE: To evaluate the influence of age, sex, body mass index (BMI), extent of meniscal resection, cartilage status, and knee load on the development of radiographically evident osteoarthritis (OA) of the knee and knee symptoms after meniscal resection. METHODS: We evaluated 317 patients with no cruciate ligament injury (mean +/- SD age 54 +/- 11 years) who had undergone meniscal resection 15-22 years earlier (followup rate 70%), with radiographic and clinical examination. The Knee injury and Osteoarthritis Outcome Score was used to quantify knee-related symptoms. Sixty-eight unoperated subjects identified from national population records were included as a reference group. RESULTS: Symptomatic radiographic OA (corresponding to Kellgren/Lawrence grade \textgreater or =2) was present in 83 of 305 operated knees (27%) and 7 of 68 control knees (10%) (relative risk 2.6, 95% confidence interval [95% CI] 1.3-6.1). Patients who had undergone total meniscectomy and subjects with obesity (BMI \textgreater or =30) had a greater likelihood of tibiofemoral radiographic OA than those who had undergone partial meniscal resection and those with a BMI \textless25, respectively. Furthermore, degenerative meniscal tear, intraoperative cartilage changes, and lateral meniscectomy were associated with radiographic OA more frequently than were longitudinal tear, absence of cartilage changes, and medial meniscectomy, respectively. Symptomatic tibiofemoral or patellofemoral radiographic OA was associated with obesity, female sex, and degenerative meniscal tear. CONCLUSION: Contributing risk factors for OA development after meniscal resection are similar to risk factors for common knee OA. Systemic factors and local biomechanical factors interact. Obesity, female sex, and preexisting early-stage OA are features associated with poor self-reported and radiographic outcome. Partial meniscal resection is associated with less radiographic OA over time than is total meniscectomy.
@article{englund_risk_2004,
title = {Risk factors for symptomatic knee osteoarthritis fifteen to twenty-two years after meniscectomy},
volume = {50},
issn = {0004-3591},
doi = {10.1002/art.20489},
abstract = {{OBJECTIVE}: To evaluate the influence of age, sex, body mass index ({BMI}), extent of meniscal resection, cartilage status, and knee load on the development of radiographically evident osteoarthritis ({OA}) of the knee and knee symptoms after meniscal resection.
{METHODS}: We evaluated 317 patients with no cruciate ligament injury (mean +/- {SD} age 54 +/- 11 years) who had undergone meniscal resection 15-22 years earlier (followup rate 70\%), with radiographic and clinical examination. The Knee injury and Osteoarthritis Outcome Score was used to quantify knee-related symptoms. Sixty-eight unoperated subjects identified from national population records were included as a reference group.
{RESULTS}: Symptomatic radiographic {OA} (corresponding to Kellgren/Lawrence grade {\textgreater} or =2) was present in 83 of 305 operated knees (27\%) and 7 of 68 control knees (10\%) (relative risk 2.6, 95\% confidence interval [95\% {CI}] 1.3-6.1). Patients who had undergone total meniscectomy and subjects with obesity ({BMI} {\textgreater} or =30) had a greater likelihood of tibiofemoral radiographic {OA} than those who had undergone partial meniscal resection and those with a {BMI} {\textless}25, respectively. Furthermore, degenerative meniscal tear, intraoperative cartilage changes, and lateral meniscectomy were associated with radiographic {OA} more frequently than were longitudinal tear, absence of cartilage changes, and medial meniscectomy, respectively. Symptomatic tibiofemoral or patellofemoral radiographic {OA} was associated with obesity, female sex, and degenerative meniscal tear.
{CONCLUSION}: Contributing risk factors for {OA} development after meniscal resection are similar to risk factors for common knee {OA}. Systemic factors and local biomechanical factors interact. Obesity, female sex, and preexisting early-stage {OA} are features associated with poor self-reported and radiographic outcome. Partial meniscal resection is associated with less radiographic {OA} over time than is total meniscectomy.},
pages = {2811--2819},
number = {9},
journaltitle = {Arthritis and Rheumatism},
shortjournal = {Arthritis Rheum.},
author = {Englund, M. and Lohmander, L. S.},
date = {2004-09},
pmid = {15457449},
keywords = {Aged, Cohort Studies, Comorbidity, Disease Progression, Female, Humans, Male, Menisci, Tibial, Middle Aged, Obesity, Orthopedic Procedures, Osteoarthritis, Knee, Retrospective Studies, Risk Factors, Sex Factors, Time Factors}
}