Home About us Contact
|
Home About us Contact | ||
|
|
||
Large Population (large + population)
Terms modified by Large Population Selected AbstractsRAPID EVOLUTIONARY ESCAPE BY LARGE POPULATIONS FROM LOCAL FITNESS PEAKS IS LIKELY IN NATUREEVOLUTION, Issue 6 2005Daniel M. Weinreich Abstract Fitness interactions between loci in the genome, or epistasis, can result in mutations that are individually deleterious but jointly beneficial. Such epistasis gives rise to multiple peaks on the genotypic fitness landscape. The problem of evolutionary escape from such local peaks has been a central problem of evolutionary genetics for at least 75 years. Much attention has focused on models of small populations, in which the sequential fixation of valley genotypes carrying individually deleterious mutations operates most quickly owing to genetic drift. However, valley genotypes can also be subject to mutation while transiently segregating, giving rise to copies of the high fitness escape genotype carrying the jointly beneficial mutations. In the absence of genetic recombination, these mutations may then fix simultaneously. The time for this process declines sharply with increasing population size, and it eventually comes to dominate evolutionary behavior. Here we develop an analytic expression for Ncrit, the critical population size that defines the boundary between these regimes, which shows that both are likely to operate in nature. Frequent recombination may disrupt high-fitness escape genotypes produced in populations larger than Ncrit before they reach fixation, defining a third regime whose rate again slows with increasing population size. We develop a novel expression for this critical recombination rate, which shows that in large populations the simultaneous fixation of mutations that are beneficial only jointly is unlikely to be disrupted by genetic recombination if their map distance is on the order of the size of single genes. Thus, counterintuitively, mass selection alone offers a biologically realistic resolution to the problem of evolutionary escape from local fitness peaks in natural populations. [source] Habitual Levels of Physical Activity Influence Bone Mass in 11-Year-Old Children From the United Kingdom: Findings From a Large Population-Based Cohort,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2007Jon H Tobias MD Abstract We examined the influence of habitual levels of physical activity on bone mass in childhood by studying the relationship between accelerometer recordings and DXA parameters in 4457 11-year-old children. Physical activity was positively related to both BMD and bone size in fully adjusted models. However, further exploration revealed that this effect on bone size was modified by fat mass. Introduction: Exercise interventions have been reported to increase bone mass in children, but it is unclear whether levels of habitual physical activity also influence skeletal development. Materials and Methods: We used multivariable linear regression to analyze associations between amount of moderate and vigorous physical activity (MVPA), derived from accelerometer recordings for a minimum of 3 days, and parameters obtained from total body DXA scans in 4457 11-year-old boys and girls from the Avon Longitudinal Study of Parents and Children. The influence of different activity intensities was also studied by stratification based on lower and higher accelerometer cut-points for moderate (3600 counts/minute) and vigorous (6200 counts/minute) activity, respectively. Results: MVPA was positively associated with lower limb BMD and BMC adjusted for bone area (aBMC; p < 0.001, adjusted for age, sex, socio-economic factors, and height, with or without additional adjustment for lean and fat mass). MVPA was inversely related to lower limb bone area after adjusting for height and lean mass (p = 0.01), whereas a positive association was observed when fat mass was also adjusted for (p < 0.001). Lower limb BMC was positively related to MVPA after adjusting for height and lean and fat mass (p < 0.001), whereas little relationship was observed after adjusting for height and lean mass alone (p = 0.1). On multivariable regression analysis using the fully adjusted model, moderate activity exerted a stronger influence on lower limb BMC compared with light activity (light activity: 2.9 [1.2,4.7, p = 0.001]; moderate activity: 13.1 [10.6,15.5, p < 0.001]; regression coefficients with 95% confidence intervals and p values). Conclusions: Habitual levels of physical activity in 11-year-old children are related to bone size and BMD, with moderate activity exerting the strongest influence. The effect on bone size (as reflected by DXA-based measures of bone area) was modified by adjustment for fat mass, such that decreased fat mass, which is associated with higher levels of physical activity, acts to reduce bone size and thereby counteract the tendency for physical activity to increase bone mass. [source] Tracking the decline of the once-common butterfly: delayed oviposition, demography and population genetics in the hermit Chazara briseisANIMAL CONSERVATION, Issue 2 2010T. Kadlec Abstract Large populations, seemingly not at risk of extinction, can decline rapidly due to alteration of habitat. This appears to be the case of the butterfly Chazara briseis, which is declining in all of Central and Eastern Europe, even from apparently large areas of its steppe grassland habitats. We combined mark,recapture, allozyme electrophoresis and adult behaviour observation to study the last remaining metapopulation of this once-widespread butterfly in the Czech Republic. The total population estimate was 1300 males and 1050 females in 10 colonies within a 70 km2 landscape. Adults were long-lived, and inseminated females required several weeks before they started ovipositing. Models using realistic lengths of the preoviposition period estimated that due to background mortality, only 25,55% of the female census population lived long enough to contribute to the next generation. This demographic load was unlikely to be balanced by an increased fecundity. Allozyme electrophoresis of 22 loci revealed much higher allelic variation than in most other studies of butterflies living in small populations (mean heterozygosity: 20.7%). If expressed as per individual colony, the genetic variation did not correlate with population density, survival or longevity. This was probably due to frequent movements among colonies; during 8 weeks of adult flight, 5.1% of recaptured males and 3.6% of recaptured females moved between colonies. The high preoviposition mortality indicates that populations of this species must contain more individuals compared with populations not suffering this additional demographic load. The high allelic diversity of each single colony suggests that the population as a whole has not undergone genetic bottlenecks, but now may be facing risks of inbreeding depression due to allele frequency shifts and the possible increase of weakly deleterious alleles. In the past, high effective population sizes were maintained by frequent dispersal in dense networks of steppic grasslands. Generous habitat restoration is necessary to safeguard populations of this specialized, yet formerly common species. [source] Population-based case,control study of oral ketoconazole treatment for birth outcomesCONGENITAL ANOMALIES, Issue 1 2005Zoltán Kazy ABSTRACT The objective of the study presented here was to check the effect of oral ketoconazole treatment on fetal development. Ketoconazole has been given a teratogenic classification of C by the US Food and Drug Administration, but human controlled epidemiological studies of the treatment's effects have not been reported. The occurrence of ketoconazole use in the second to third months of gestation was compared between cases with congenital abnormalities and their matched controls in the large population-based data set of the Hungarian Case,Control Surveillance of Congenital Abnormalities, 1980,1996. Birth weight and gestational age were evaluated in control newborn infants born to mothers with or without ketoconazole treatment. The case group comprised 22 843 cases with congenital abnormalities, while the control group contained 38 151 newborn infants without any defects. Six infants (0.03%) and 12 controls (0.03%) had mothers who had received oral ketoconazole treatment (prevalence odds ratio: with 95% confidence interval: 0.8, 0.3,2.2). No group of infants with congenital abnormalities had mothers with a higher incidence of use of the drug. The mean gestational age was somewhat longer while birth weight was somewhat larger in controls with ketoconazole treated mothers. Our study failed to demonstrate a higher rate of congenital abnormalities in infants with mothers who had received oral ketoconazole treatment during pregnancy. [source] Rapid and easy semi-quantitative evaluation method for diacylglycerol and inositol-1,4,5-trisphosphate generation in orexin receptor signallingACTA PHYSIOLOGICA, Issue 3 2010M. E. Ekholm Abstract Aim:, Fluorescent protein-based indicators have enabled measurement of intracellular signals previously nearly inaccessible for studies. However, indicators showing intracellular translocation upon response suffer from serious limitations, especially the very time-consuming data collection. We therefore set out in this study to evaluate whether fixing and counting cells showing translocation could mend this issue. Methods:, Altogether three different genetically encoded indicators for diacylglycerol and inositol-1,4,5-trisphosphate were transiently expressed in Chinese hamster ovary cells stably expressing human OX1 orexin receptors. Upon stimulation with orexin-A, the cells were fixed with six different protocols. Results:, Different protocols showed clear differences in their ability to preserve the indicator's localization (i.e. translocation after stimulus) and its fluorescence, and the best results for each indicator were obtained with a different protocol. The concentration,response data obtained with cell counting are mostly comparable to the real-time translocation and biochemical data. Conclusion:, The counting method, as used here, works at single time point and looses the single-cell-quantitative aspect. However, it also has some useful properties. First, it easily allows processing of a 100- to 1000-fold higher cell numbers than real-time imaging producing statistically consistent population-quantitative data much faster. Secondly, it does not require expensive real-time imaging equipment. Fluorescence in fixed cells can also be quantitated, though this analysis would be more time-consuming than cell counting. Thirdly, in addition to the quantitative data collection, the method could be applied for identifying responsive cells. This might be very useful in identification of e.g. orexin-responding neurones in a large population of non-responsive cells in primary cultures. [source] Are symptoms of depression more common in diabetes?DIABETIC MEDICINE, Issue 11 2008Results from the Heinz Nixdorf Recall study Abstract Aims To estimate the association between depressive symptoms and Type 2 diabetes, as well as previously undetected diabetes, in a large population-based sample in Germany and to determine associated variables. Methods We used baseline data on 4595 participants (age 45,75 years, 50.2% women) from the German Heinz Nixdorf Recall study, a population-based, prospective cohort study which started in 2000. Diabetes mellitus was assessed by self report (physician diagnosis or medication), undiagnosed diabetes based on blood glucose levels. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale short form (cut-off , 15 points). We fitted multiple logistic regression models. Results The prevalence of diagnosed and previously undetected diabetes was 9.3% (95% confidence interval 8.2,11.6) and 7.6% (6.6,8.8) in men and 6.0% (5.1,7.1) and 3.2% (2.5,4.0) in women, respectively. Compared with non-diabetic women, the prevalence of depressive symptoms was not significantly different in diabetic women (age-adjusted odds ratio, 95% confidence interval 1.48; 0.98,2.24) and women with undiagnosed diabetes (0.67; 0.33,1.36). In men, the prevalence of depressive symptoms tended to be lower in diabetic than in non-diabetic subjects (0.62; 0.35,1.09), but the depressive symptoms were significantly less frequent in men with undiagnosed diabetes (0.30; 0.13,0.70). The pattern remained after further adjustment. Significant associations with depressive symptoms were found for co-morbidities and living without a partner in both women and in men, and for body mass index and activity level in women only. Conclusions After adjustment for relevant covariates, the association between depressive symptoms and Type 2 diabetes was heterogenous in our population-based study. In subjects with undiagnosed diabetes, however, depressive symptoms were less frequent in men. Co-morbidities and psychosocial conditions are strongly associated with depressive symptoms. [source] No clear genetic influences on the association between dyslexia and anxiety in a population-based sample of female twinsDYSLEXIA, Issue 4 2009Andrew J.O. Whitehouse Abstract Individuals with dyslexia are at an increased risk for anxiety disorders (e.g. generalized anxiety disorder, stress disorders, panic disorder). The extent to which this association is mediated by genetic and/or environmental influences is unclear. The current study explored the relationship between these two phenotypes using a large population-based twin sample. In total, 940 monozygotic and 903 dizygotic female twin pairs were included in the analyses. The presence of dyslexia and anxiety was determined by self-report of diagnosis by a health professional. Tetrachoric correlations confirmed an association between the two phenotypes, but suggested that there was no evidence for shared genetic risks. Bivariate twin modelling corroborated this finding and indicated the relationship between dyslexia and anxiety is mediated by shared environmental factors. Future research should seek to identifying the environmental factors that increase the vulnerability of individuals with dyslexia to emotional problems should be a priority for future research. Copyright © 2008 John Wiley & Sons, Ltd. [source] Estimating the number of alcohol-attributable deaths: methodological issues and illustration with French data for 2006ADDICTION, Issue 6 2010Grégoire Rey ABSTRACT Aims Computing the number of alcohol-attributable deaths requires a series of hypotheses. Using French data for 2006, the potential biases are reviewed and the sensitivity of estimates to various hypotheses evaluated. Methods Self-reported alcohol consumption data were derived from large population-based surveys. The risks of occurrence of diseases associated with alcohol consumption and relative risks for all-cause mortality were obtained through literature searches. All-cause and cause-specific population alcohol-attributable fractions (PAAFs) were calculated. In order to account for potential under-reporting, the impact of adjustment on sales data was tested. The 2006 mortality data were restricted to people aged between 15 and 75 years. Results When alcohol consumption distribution was adjusted for sales data, the estimated number of alcohol-attributable deaths, the sum of the cause-specific estimates, was 20 255. Without adjustment, the estimate fell to 7158. Using an all-cause mortality approach, the adjusted number of alcohol-attributable deaths was 15 950, while the non-adjusted estimate was a negative number. Other methodological issues, such as computation based on risk estimates for all causes for ,all countries' or only ,European countries', also influenced the results, but to a lesser extent. Discussion The estimates of the number of alcohol-attributable deaths varied greatly, depending upon the hypothesis used. The most realistic and evidence-based estimate seems to be obtained by adjusting the consumption data for national alcohol sales, and by summing the cause-specific estimates. However, interpretation of the estimates must be cautious in view of their potentially large imprecision. [source] Cognitive test scores in male adolescent cigarette smokers compared to non-smokers: a population-based studyADDICTION, Issue 2 2010Mark Weiser ABSTRACT Background Although previous studies indicate that people with lower intelligence quotient (IQ) scores are more likely to become cigarette smokers, IQ scores of siblings discordant for smoking and of adolescents who began smoking between ages 18,21 years have not been studied systematically. Methods Each year a random sample of Israeli military recruits complete a smoking questionnaire. Cognitive functioning is assessed by the military using standardized tests equivalent to IQ. Results Of 20 221 18-year-old males, 28.5% reported smoking at least one cigarette a day (smokers). An unadjusted comparison found that smokers scored 0.41 effect sizes (ES, P < 0.001) lower than non-smokers; adjusted analyses remained significant (adjusted ES = 0.27, P < 0.001). Adolescents smoking one to five, six to 10, 11,20 and 21+ cigarettes/day had cognitive test scores 0.14, 0.22, 0.33 and 0.5 adjusted ES poorer than those of non-smokers (P < 0.001). Adolescents who did not smoke by age 18, and then began to smoke between ages 18,21 had lower cognitive test scores compared to never-smokers (adjusted ES = 0.14, P < 0.001). An analysis of brothers discordant for smoking found that smoking brothers had lower cognitive scores than non-smoking brothers (adjusted ES = 0.27; P = 0.014). Conclusion Controlled analyses from this large population-based cohort of male adolescents indicate that IQ scores are lower in male adolescents who smoke compared to non-smokers and in brothers who smoke compared to their non-smoking brothers. The IQs of adolescents who began smoking between ages 18,21 are lower than those of non-smokers. Adolescents with poorer IQ scores might be targeted for programmes designed to prevent smoking. [source] Recurrence after a First Unprovoked Cryptogenic/Idiopathic Seizure in Children: A Prospective Study from São Paulo, BrazilEPILEPSIA, Issue 2 2004Anna E. Scotoni Summary: Purpose: To evaluate the recurrence risk after a first unprovoked seizure in a large population of children and adolescents of a developing country. Methods: This prospective study was conducted at two tertiary hospitals, between September 1989 and August 1998. Children were enrolled if they had a first unprovoked cryptogenic/idiopathic seizure and maximal interval to the enrollment ,90 days. EEG and computed tomography (CT) were performed in most patients. Potential predictors of recurrence were compared by using the Cox proportional hazards model in univariate and multivariate analyses. Survival analysis was performed by using the Kaplan,Meier curves. Results: Two hundred thirteen children were included. Recurrence occurred in 34% of the patients, and mean time for recurrence was 12 months. Statistical analysis showed significance for seizure recurrence only for patients with abnormal EEGs. CT was performed in 182 patients, and abnormalities were found in 9.5%. Small calcifications were the most frequent finding, and this was not a predictor for recurrence. Conclusions: The risk of recurrence after a first unprovoked seizure in children from a developing country is similar to that found in developed countries. An abnormal EEG is a risk factor for seizure recurrence in children with a cryptogenic/idiopathic seizure. Calcifications on CT do not increase the risk of recurrence. [source] Pregnancy outcome in congenital dyserythropoietic anemia type IEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2008Hanna Shalev Abstract Objectives:, Congenital dyserythropoietic anemia type I (CDA I) is a rare inherited disease characterized by moderate to severe macrocytic anemia and abnormal erythroid precursors with nuclear chromatin bridges and spongy heterochromatin. Moderate to severe maternal anemia is a recognized independent risk factor for low birth weight (LBW) and complicated delivery. The aim of the study was to review the outcome of pregnancies in women with CDA I. Methods:, The clinical and laboratory records of 28 spontaneous pregnancies in six Bedouin women with CDA I were reviewed. The results were compared with findings from a retrospective review of a large population-based registry including all pregnancies in Bedouin women during the same 15-yr period. Results:, Eighteen pregnancies in women with CDA I (64%) were complicated. One pregnancy was aborted spontaneously in the first trimester and one resulted in a non-viable fetus (stillborn at 26 wk). Cesarean section (CS) was performed in 10 pregnancies (36%). Eleven of the 26 newborns (42%) had a LBW: six were born prematurely and five were small for gestational age. The odds ratio for CS in women with CDA I compared with healthy Bedouin women was 4.5 [95% confidence interval (CI) 1.2,10.3], and for a LBW infant, 5.5 (95% CI 2.4,12.3). Careful follow-up was associated with significantly better fetal outcome (P = 0.05). Conclusions:, Pregnancies in women with CDA I are at high risk for delivery-related and outcome complications. To improve fetal outcome, women with CDA I should be carefully monitored during pregnancy. [source] High prevalence of restless legs syndrome in multiple sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2007M. Manconi Despite the fact that multiple sclerosis (MS) patients often include leg restlessness as a sensory symptom, MS is not mentioned amongst symptomatic restless legs syndrome (RLS) forms. The aim of this study was to estimate RLS prevalence in a large population of MS patients, comparing clinical and MRI findings between patients with and without RLS. Each of the 156 MS patients (100 females, 56 males, mean age 40.7 ± 10.4) enrolled in a prospective study underwent a medical history interview, a neurological examination with the assessment of the Expanded Disability Status Scale (EDSS), and a structured questionnaire to verify the presence and features of RLS. Conventional brain,spinal MRIs of 99 subjects were also evaluated and compared between patients with and without RLS. Fifty-one subjects (32.7%) (mean age 43.8 ± 12.8) met the criteria for RLS. In a few patients (8.5%), the RLS preceded clinical MS onset, whilst in the remaining cases the RLS was followed by or was simultaneous with clinical MS onset. Comparing the RLS group with the group without RLS, no significant differences were found in MS duration, gender, and referred sleep habits. The primary progressive MS course was more represented in the RLS group, which also showed a higher EDSS score. RLS is a very common finding in MS patients and should be considered amongst the symptomatic RLS forms. RLS is also associated with higher disability. [source] Headache prevalence related to smoking and alcohol use.EUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2006The Head-HUNT Study The aim of this study was to examine a possible association between smoking, alcohol and headache in a large population-based cross-sectional study. A total of 51 383 subjects completed a headache questionnaire and constituted the ,Head-HUNT' Study. Questionnaire-based information on smoking was available in 95% and on alcohol in 89% of the individuals. Associations were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals (CI). Prevalence rates for headache were higher amongst smokers compared with never smokers, most evident for those under 40 years smoking more than 10 cigarettes per day (OR 1.5, 95% CI 1.3,1.6). Passive smoking was also associated with higher headache prevalence. For alcohol use, there was a tendency of decreasing prevalence of migraine with increasing amounts of alcohol consumption compared with alcohol abstinence. Only with regard to symptoms indicating alcohol overuse, a positive association with frequent headache was found. The association between headache and smoking found in the present study raises questions about a causal relationship, e.g. that smoking causes headache or that it allays stress induced by headache. The observed negative association between migraine and alcohol consumption is probably explained by the headache precipitating properties of alcohol. [source] Cerebral vasospasm and ischaemic infarction in clipped and coiled intracranial aneurysm patientsEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2002M. Hohlrieder The influence of the treatment modalities (clipping/coiling) on the incidence of vasospasm and ischaemic infarction in aneurysm patients is still judged controversially. The purpose of this study was to analyse and compare retrospectively cerebral vasospasm and ischaemic infarction, as well as neurological deficits and outcome within a large population of clipped and coiled patients with ruptured and unruptured aneurysms. Within a 2-year period, a total of 144 interventions (53 clipping/91 coiling) entered the study. Daily bilateral transcranial Doppler sonographic monitoring was performed to observe vasospasm development. All cerebral computed tomography (cCT) and magnetic resonance imaging (MRI) scans were reviewed with respect to occurrence and localization of ischaemic infarctions. Focal neurological deficits were recorded and clinical outcome was evaluated using the Glasgow Outcome Scale. Statistical analysis included the use of multivariate logistic regression models to find determinants of vasospasm, ischaemic infarction and neurological deficits. Altogether, vasospasm was detected after 77 (53.5%) interventions, 61.8% in females (P < 0.01). Clipped patients significantly more often exhibited vasospasms (69.8 vs. 44.0%, P < 0.005) and were treated 1 week longer at the intensive care unit (P < 0.005). Seventy-seven patients (53.5%) developed ischaemic infarctions, 62.3% after clipping and 48.4% after coiling (P > 0.05). In the multivariate analysis, aneurysm-rupture was the strongest predictor for vasospasm and vasospasm was the strongest predictor for infarction. Neurological deficits at discharge (46.5%) were independent of treatment modality, the same applied for the mean Glasgow Outcome Scores. There was no significant difference in mortality between surgical and endovascular treatment (9.4 vs. 12.1%). Whilst the vasospasm incidence was significantly higher after surgical treatment, ischaemic infarctions were only slightly more frequent. The incidence of neurological deficits and clinical outcome was similar in both treatment groups. [source] Odor vapor pressure and quality modulate local field potential oscillatory patterns in the olfactory bulb of the anesthetized ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2008Tristan Cenier Abstract A central question in chemical senses is the way that odorant molecules are represented in the brain. To date, many studies, when taken together, suggest that structural features of the molecules are represented through a spatio-temporal pattern of activation in the olfactory bulb (OB), in both glomerular and mitral cell layers. Mitral/tufted cells interact with a large population of inhibitory interneurons resulting in a temporal patterning of bulbar local field potential (LFP) activity. We investigated the possibility that molecular features could determine the temporal pattern of LFP oscillatory activity in the OB. For this purpose, we recorded the LFPs in the OB of urethane-anesthetized, freely breathing rats in response to series of aliphatic odorants varying subtly in carbon-chain length or functional group. In concordance with our previous reports, we found that odors evoked oscillatory activity in the LFP signal in both the beta and gamma frequency bands. Analysis of LFP oscillations revealed that, although molecular features have almost no influence on the intrinsic characteristics of LFP oscillations, they influence the temporal patterning of bulbar oscillations. Alcohol family odors rarely evoke gamma oscillations, whereas ester family odors rather induce oscillatory patterns showing beta/gamma alternation. Moreover, for molecules with the same functional group, the probability of gamma occurrence is correlated to the vapor pressure of the odor. The significance of the relation between odorant features and oscillatory regimes along with their functional relevance are discussed. [source] Role of GABAA inhibition in modulation of pyramidal tract neuron activity during postural correctionsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2007Zinaida A. Tamarova Abstract In a previous study we demonstrated that the activity of pyramidal tract neurons (PTNs) of the motor cortex is modulated in relation to postural corrections evoked by periodical tilts of the animal. The modulation included an increase in activity in one phase of the tilt cycle and a decrease in the other phase. It is known that the motor cortex contains a large population of inhibitory GABAergic neurons. How do these neurons participate in periodic modulation of PTNs? The goal of this study was to investigate the role of GABAA inhibitory neurons of the motor cortex in the modulation of postural-related PTN activity. Using extracellular electrodes with attached micropipettes, we recorded the activity of PTNs in cats maintaining balance on a tilting platform both before and after iontophoretic application of the GABAA receptor antagonists gabazine or bicuculline. The tilt-related activity of 93% of PTNs was affected by GABAA receptor antagonists. In 88% of cells, peak activity increased by 75 ± 50% (mean ± SD). In contrast, the trough activity changed by a much smaller value and almost as many neurons showed a decrease as showed an increase. In 73% of the neurons, the phase position of the peak activity did not change or changed by no more than 0.1 of a cycle. We conclude that the GABAergic system of the motor cortex reduces the posture-related responses of PTNs but has little role in determining their response timing. [source] Arm trajectory and representation of movement processing in motor cortical activityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2000Andrew B. Schwartz Abstract We review experiments in which single-cell primary motor cortical activity was recorded from Rhesus monkeys (Macaca mulatta) while they performed reaching and drawing tasks. The directional tuning curves generated during reaching were modulated by the speed of movement and this was reflected in the magnitude of population vectors calculated from firing rates of a large population of cells. Directional and speed representation in the firing rates of these cells is robust across both reaching and drawing. Several behavioural invariants related to the speed of drawing were represented in the time-series of population vectors. This high fidelity neural representation of velocity found in motor cortex can be used to visualize the dynamics of motor cortical activity during drawing and suggests that the cost function governing the rate of drawing is bound by neural processing. [source] Archaeofacies analysis: Using depositional attributes to identify anthropic processes of deposition in a monumental shell mound of Santa Catarina State, southern BrazilGEOARCHAEOLOGY: AN INTERNATIONAL JOURNAL, Issue 3 2009Ximena S. Villagran In the coast of Santa Catarina State (southern Brazil), a large population of monumental shell mounds characterizes a highly dynamic coastal setting. In this paper, sedimentary facies analysis was adapted for description, sampling, and interpretation of shell mound complex and repetitive archaeostratigraphic successions. Archaeofacies identification in the field, according to depositional attributes, is tested by contrasting field description with multi-element chemical analyses, total carbon and nitrogen determinations, and micromorphological descriptions. Two vertical sequences at the black deposit of Jabuticabeira II shell mound were studied and preliminary results showed that: (1) depositional attributes are a reliable base for archaeofacies identification in the field, (2) the formation process of this site involved a sequence of anthropic depositional processes, where burned refuse was redeposited over the shell mound following a ritual construction pattern, and (3) the black deposit includes a double palimpsest that refers to provenance and meaning of mound construction material. © 2009 Wiley Periodicals, Inc. [source] Genetic susceptibility to tobacco smoke toxicity and chronic obstructive pulmonary diseaseGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1 2002Shinji Teramoto Because elderly patients with chronic obstructive pulmonary disease are often overlooked, screening efforts are at the moment directed at higher risk subjects such as heavy smokers with obstructive airways disease. Because only 10,20% of heavy smokers developed symptomatic airflow obstruction, a different genetic susceptibility to cigarette smoke-lung injury is implicated in the pathogenesis of chronic obstructive pulmonary disease. Several candidate gene polymorphisms are proposed as the genetic risk for the development of chronic obstructive pulmonary disease. The current candidates are the polymorphisms in the 3, non-coding region of the ,1-antitypsin gene, ,1-antichymotrypsin gene, tumor necrosis factor- , gene, microsomal epoxide hydrolase gene, and glutathione S- transferase P1 gene, and microsatellite polymorphism in the heme oxygenase-1 gene promoter. However, the results are variously reported between Japanese and Caucasians. The association studies of the polymorphisms with chronic obstructive pulmonary disease require further confirmation in different ethnic groups by other researchers using a large population. The current strategy and pitfalls of the gene explorations of chronic obstructive pulmonary disease are discussed. [source] Racial Differences in the Receipt of Bowel Surveillance Following Potentially Curative Colorectal Cancer SurgeryHEALTH SERVICES RESEARCH, Issue 6p2 2003Gary L. Ellison Objective. To investigate racial differences in posttreatment bowel surveillance after colorectal cancer surgery in a large population of Medicare patients. Data Sources. We used a large population-based dataset: Surveillance, Epidemiology, and End Results (SEER) linked to Medicare data. Study Design. This is a retrospective cohort study. We analyzed data from 44,768 non-Hispanic white, 2,921 black, and 4,416 patients from other racial/ethnic groups, aged 65 and older at diagnosis, who had a diagnosis of local or regional colorectal cancer between 1986 and 1996, and were followed through December 31, 1998. Cox Proportional Hazards models were used to investigate the relation of race and receipt of posttreatment bowel surveillance. Data Collection. Sociodemographic, hospital, and clinical characteristics were collected at the time of diagnosis for all members of the cohort. Surgery and bowel surveillance with colonoscopy, sigmoidoscopy, and barium enema were obtained from Medicare claims using ICD-9-CM and CPT-4 codes. Principal Findings. The chance of surveillance within 18 months of surgery was 57 percent, 48 percent, and 45 percent for non-Hispanic whites, blacks, and others, respectively. After adjusting for sociodemographic, hospital, and clinical characteristics, blacks were 25 percent less likely than whites to receive surveillance if diagnosed between 1991 and 1996 (RR=0.75, 95 percent CI=0.70,0.81). Conclusions. Elderly blacks were less likely than non-Hispanic whites to receive posttreatment bowel surveillance and this result was not explained by measured racial differences in sociodemographic, hospital, and clinical characteristics. More research is needed to explore the influences of patient- and provider-level factors on racial differences in posttreatment bowel surveillance. [source] BRCA1 and BRCA2 in Indian breast cancer patients,,HUMAN MUTATION, Issue 6 2002Sunita Saxena Abstract Incidence of breast cancer in Indian women is not as high as in Western countries, nonetheless age-adjusted incidence rates (AAR) have risen from 17.9 to 24.9 per 100,000 from 1965 to 1985. Although these rates are still approximately one quarter to one third of incidence rates in North America and Europe, respectively, due to the large population of women at risk, nearly 80,000 new cases were diagnosed in India in 2000. Although identification of BRCA1 and BRCA2 has greatly increased our understanding of breast cancer genetics in populations of Western European descent, the role of these genes in Indian populations remains unexplored. Analysis of a series of 20 breast cancer patients from North India with either family history of breast and/or ovarian cancer (2 or more affected first degree relatives) or early age of onset (<35 years) led to identification of two novel splice variants (331+1G>T; 4476+2T>C) in BRCA1 (10%). In addition, two BRCA2 missense variants were each identified in more than one patient (two unrelated individuals each) and likely represent population-specific polymorphisms. © 2002 Wiley-Liss, Inc. [source] The G51S purine nucleoside phosphorylase polymorphism is associated with cognitive decline in Alzheimer's disease patientsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2007Emanuela Tumini Abstract Alzheimer's disease (AD) is a polygenic and multifactorial complex disease, whose etiopathology is still unclear, however several genetic factors have shown to increase the risk of developing the disease. Purine nucleotides and nucleosides play an important role in the brain. Besides their role in neurotransmission and neuromodulation, they are involved in trophic factor release, apoptosis, and inflammatory responses. These mediators may also have a pivotal role in the control of neurodegenerative processes associated with AD. In this report the distribution of the exonic G/A single nucleotide polymorphism (SNP) in purine nucleoside phosphorylase (PNP) gene, resulting in the amino acid substitution serine to glycine at position 51 (G51S), was investigated in a large population of AD patients (n,=,321) and non-demented control (n,=,208). The PNP polymorphism distribution was not different between patients and controls. The polymorphism distribution was also analyzed in AD patients stratified according to differential progressive rate of cognitive decline during a 2-year follow-up. An increased representation of the PNP AA genotype was observed in AD patients with fast cognitive deterioration in comparison with that from patients with slow deterioration rate. Our findings suggest that the G51S PNP polymorphism is associated with a faster rate of cognitive decline in AD patients, highlighting the important role of purine metabolism in the progression of this neurodegenerative disorder. Copyright © 2007 John Wiley & Sons, Ltd. [source] T cells developing in fetal thymus of T-cell receptor ,-chain transgenic mice colonize ,, T-cell-specific epithelial niches but lack long-term reconstituting potentialIMMUNOLOGY, Issue 1 2006Karin Leandersson Summary The ,, T cells generated during mouse fetal development are absolutely dependent on their invariant T-cell receptors (TCRs) for their function. However, there is little information on whether the epithelial homing properties of fetal T cells might also be developmentally induced by factors unrelated to TCR specificity. We have previously described TCR ,-chain transgenic (2B4 TCR-, TG) mice, in which the transgenic TCR ,-chain is expressed early, already at embryonic day 14 (E14). These mice have a large population of ,,, T-cell-like' CD4, CD8, (double-negative; DN) ,, T cells, some of which develop during E14,E18 contemporarily to intraepithelial lymphocytes (IELs) expressing invariant TCR-,,. Using the 2B4 TCR-, TG mouse model we have been able to more precisely study the impact of a variant TCR expression on IEL development and homing. In this study we show that TCR-, TG and TCR-, TG crossed to TCR-,-deficient mice (TCR-, TG × TCR-,,/,) carry TG TCR-,+ dendritic epidermal T cells (DETCs) and TCR-, TG+ IELs in the small intestine. The TG+ DETCs develop and seed the epidermis with similar kinetics as V,5+ DETCs of normal mice, in contrast to the TCR-,,+ DETCs found in TCR-,,/, mice. However, whereas the intestinal TCR-, TG+ IELs persist in old mice (> 20 months), the TCR-, TG+ DETCs do not. The data in this study indicate that the timing of TCR expression and thereby development during ontogeny regulates the specific homing potential for fetal T cells but not their subsequent functions and properties. [source] Radical Polymers for Organic Electronic Devices: A Radical Departure from Conjugated Polymers?ADVANCED MATERIALS, Issue 22 2009Kenichi Oyaizu Abstract Radical polymers are aliphatic or nonconjugated polymers bearing organic robust radicals as pendant groups per repeating unit. A large population of the radical redox sites allows the efficient redox gradient-driven electron transport through the polymer layer by outer-sphere self-exchange reactions in electrolyte solutions. The radical polymers are emerging as a new class of electroactive materials useful for various kinds of wet-type energy storage, transport, and conversion devices. Electric-field-driven charge transport by hopping between the densely populated radical sites is also a remarkable aspect of the radical polymers in the solid state, which leads to many dry-type devices such as organic memories, diodes, and switches. [source] Coffee consumption and risk of colorectal cancer in a population-based prospective cohort of Japanese men and womenINTERNATIONAL JOURNAL OF CANCER, Issue 6 2007Kyung-Jae Lee Abstract We prospectively examined the association between coffee consumption and the risk of developing colorectal cancer in a large population-based cohort study (the JPHC Study) of Japanese men and women. Data were analyzed from a population-based cohort of 96,162 subjects (46,023 men and 50,139 women). A total of 1,163 incident colorectal cancers were identified during the follow-up period, including 763 cases of colon cancer and 400 of rectal cancer. We observed a significant inverse association between coffee consumption and the risk of developing invasive colon cancer among women. Compared with those who almost never consumed coffee, women who regularly consumed 3 or more cups of coffee per day had a RR of 0.44 (95% CI = 0.19,1.04; p for trend = 0.04) after adjustment for potential confounding factors. However, no significant association was found for rectal cancer in women. In men, no significant decrease was observed in any colorectal cancer site. Further, additional analyses on the association of green tea consumption with colorectal cancer risk found no significant association in men or women. These findings suggest that coffee consumption may lower the risk of colon cancer among Japanese women. © 2007 Wiley-Liss, Inc. [source] Impact of reproductive factors and lactation on breast carcinoma in situ riskINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Kathleen Meeske Abstract Incidence rates for breast carcinoma in situ (CIS) have increased markedly over the past 20 years. Breast CIS, detected primarily on mammography, now represents 30,45% of all screened detected breast cancers. We conducted a large population-based case-control study to evaluate the impact of reproductive factors and lactation on breast CIS risk. Case subjects were newly diagnosed with breast CIS at ages 35,64 years between March 1, 1995 and May 31, 1998 (n = 567), resided in Los Angeles County and were born in the United States. Control subjects (n = 614), identified through random digit dialing, fulfilled the same eligibility criteria and were required to have had at least one screening mammogram in the 2-year period before their interview. Women with a positive family history of breast cancer had a 2-fold increase in breast CIS risk. Parous women were at reduced risk relative to nulligravid women (odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.46,1.00). Among nulliparous women, pregnancy was unrelated to breast CIS risk. Among parous women, risk declined with each additional term pregnancy (p -trend = 0.003). No associations were found with age at first term pregnancy, induced abortion or miscarriage. Long duration of breast-feeding (,24 months) was associated with increased risk (OR = 2.00, 95% CI = 1.11,3.60). The observed effects of family history and pregnancy on breast CIS risk are consistent with those observed for invasive breast cancer. The results for breast-feeding are contrary to what has been observed in studies of invasive breast cancer. © 2004 Wiley-Liss, Inc. [source] Mild cognitive impairment in the older population: Who is missed and does it matter?INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 8 2008Blossom C. M. Stephan Abstract Objectives Classifications of mild cognitive impairment (MCI) vary in the precision of the defining criteria. Their value in clinical settings is different from population settings. This difference depending on setting is to be expected, but must be well understood if population screening for dementia and pre-dementia states is to be considered. Of importance is the impact of missed diagnosis. The magnitude of missed ,at-risk' cases in the application of different MCI criteria in the population is unknown. Methods Data were from the Medical Research Council Cognitive Function and Ageing Study, a large population based study of older aged individuals in the UK. Prevalence and two-year progression to dementia in individuals whose impairment failed to fulfil published criteria for MCI was evaluated. Results Prevalence estimates of individuals not classified from current MCI definitions were extremely variable (range 2.5,41.0%). Rates of progression to dementia in these non-classified groups were also very variable (3.7,30.0%), reflecting heterogeneity in MCI classification requirements. Conclusions Narrow definitions of MCI developed for clinical settings when applied in the population result in a large proportion of individuals who progress to dementia being excluded from MCI classifications. More broadly defined criteria would be better for selection of individuals at risk of dementia in population settings, but at the possibility of high false positive rates. While exclusion may be a good thing in the population since most people are presumably ,normal', over-inclusion is more likely to be harmful. Further work needs to investigate the best classification system for application in the population. Copyright © 2008 John Wiley & Sons, Ltd. [source] The Influence of an Insulin-Like Growth Factor I Gene Promoter Polymorphism on Hip Bone Geometry and the Risk of Nonvertebral Fracture in the Elderly: The Rotterdam Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2004Fernando Rivadeneira Abstract The absence of the wildtype allele of a promoter polymorphism of the IGF-I gene is associated with increased risk (1.5; 95% CI, 1.1-2.0) of fragility fracture in women (n = 4212) but not in men (n = 2799). An approximation of hip bone geometry (from DXA) suggested the polymorphism is associated with bone strength and stability in gender-specific ways. Introduction: Previously, we found a CA-repeat promoter polymorphism in the insulin-like growth factor I (IGF-I) gene associated with IGF-I levels and BMD in postmenopausal women, but the relationship with fractures is unclear. In this large population-based study of elderly men and women, we examined the association between this IGF-I promoter polymorphism with parameters of bone geometry and the occurrence of fractures. Material and Methods: Within the Rotterdam Study, a prospective population-based cohort, the IGF-I polymorphism was analyzed in relation to incident nonvertebral fractures in 2799 men and 4212 women followed on average for 8.6 years. Furthermore, we estimated structural parameters of hip bone geometry indirectly from DXA outputs of the femoral neck in 2372 men and 3114 women. We studied neck width, cortical thickness, and the cortical buckling ratio and the section modulus as indexes of bone stability and bending strength. Results: Women heterozygotes and noncarriers of the allele had, respectively, 1.2 (95% CI, 1.0-1.5) and 1.5 (95% CI, 1.1-2.0) increased risk of having a fragility fracture at older age compared with homozygotes for the 192-bp allele (p trend = 0.0007). In men, fracture risk was not influenced by the polymorphism. Compared with homozygotes for the 192-bp allele, noncarrier males had ,1% narrower femoral necks and 2.2% lower section moduli (p trend < 0.05). Noncarrier females had 1.7% thinner cortices and 1.6% higher buckling ratios (p trend < 0.05) but no significant differences in femoral neck widths and section moduli. In women with low body mass index, genotype differences in bone strength (section modulus) and fracture risk were accentuated (p interaction = 0.05). The genotype-dependent differences in hip bone geometry did not fully explain the genotype-dependent differences in fracture risk. Conclusions: The CA-repeat promoter polymorphism in the IGF-I gene is associated with the risk for fragility fracture at old age in women and with bone structure in both genders. [source] Simultaneous Atrial and Ventricular Anti-Tachycardia Pacing as a Novel Method of Rhythm DiscriminationJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2006SAMIR SABA M.D. Background: Inappropriate shocks remain a problem in patients with defibrillators (ICD). Objective: To evaluate a new discrimination algorithm for supraventricular (SVT) and ventricular (VT) tachycardias, based on the response to simultaneous (A+V) atrial (A) and ventricular (V) anti-tachycardia pacing (ATP). Methods: Patients undergoing electrophysiological testing or dual-chamber implantable cardioverter-defibrillator (ICD) implantation were enrolled (N = 32) and underwent A+V ATP through a Marquis ICD with investigational software. If persisting after ATP, the rhythm was classified as VT if the first electrical event was sensed on the V channel and as an SVT otherwise. Results: Arrhythmia sequences (N = 275; 53 VT; 222 SVT) were analyzed in 26 patients (age = 51 ± 17 years, 13 men, LVEF = 0.49 ± 0.14). In response to A+V ATP, 55% of SVT versus 41% of VT episodes were terminated (P = NS). Termination of VT but not of SVT was more likely with faster (50% at ATP/arrhythmia cycle length (CL) = 0.81 vs 8% at ATP/arrhythmia CL = 0.88, P = 0.02) but not with longer ATP bursts (P = NS). Of the 115 arrhythmias that persisted after A+V ATP, the algorithm correctly classified 24 of 24 VT (GEE-adjusted sensitivity = 100%) and 85 of 91 SVT (GEE-adjusted specificity = 93%). Proarrhythmia was noted after two A+V ATP, in the form of atrial fibrillation induction and VT acceleration. Conclusions: We describe a new algorithm that can discriminate between SVT and VT with a high sensitivity and specificity. This form of ATP can terminate 55% of SVT sequences. The performance of this new algorithm merits further testing in a large population of dual-chamber ICD patients. [source] S100A6 (calcyclin) deficiency induces senescence-like changes in cell cycle, morphology and functional characteristics of mouse NIH 3T3 fibroblastsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2010omnicki, ukasz P. S Abstract S100A6 (calcyclin) is a calcium binding protein with two EF-hand structures expressed mostly in fibroblasts and epithelial cells. We have established a NIH 3T3 fibroblast cell line stably transfected with siRNA against S100A6 to examine the effect of S100A6 deficiency on non-transformed cell physiology. We found that NIH 3T3 fibroblasts with decreased level of S100A6 manifested altered cell morphology and proliferated at a much slower pace than the control cells. Cell cycle analysis showed that a large population of these cells lost the ability to respond to serum and persisted in the G0/G1 phase. Furthermore, fibroblasts with diminished S100A6 level exhibited morphological changes and biochemical features of cellular senescence as revealed by ,-galactosidase and gelatinase assays. Also, S100A6 deficiency induced changes in the actin cytoskeleton and had a profound impact on cell adhesion and migration. Thus, we have shown that the S100A6 protein is involved in multiple aspects of fibroblast physiology and that its presence ensures normal fibroblast proliferation and function. J. Cell. Biochem. 109: 576,584, 2010. © 2009 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||||||||||||||