bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of antiretroviral choice on hypercholesterolaemia events: the role of the nucleoside reverse transcriptase inhibitor backbone
Authors: Jones R , Sawleshwarkar S , Michailidis C , Jackson A , Mandalia S , Stebbing J , Bower M , Nelson M , Gazzard BG , Moyle GJ 
Published: October 2005

BackgroundThe use of highly active antiretroviral therapy (HAART) has profoundly altered the life expectancy of individuals infected with HIV. Metabolic abnormalities associated with antiretrovirals and cumulative exposure to combination antiretroviral therapy, including dyslipidaemia and insulin resistance, have been linked to an increased risk of myocardial infarction.MethodsLongitudinal data from a large prospectively collected clinical database were analysed. All patients who commenced first antiretroviral therapy (ART) [two nucleoside reverse transcriptase inhibitors (NRTIs)+one nonnucleoside reverse transcriptase inhibitor (NNRTI) or one active protease inhibitor (PI)] since 1996 were identified. Patients with elevated cholesterol levels [>5.5 mmol/L (215 mg/dL)] prior to therapy initiation were excluded. Quantitative data were categorized into quartiles and presented stratified by individuals developing abnormal levels of cholesterol during first‐line HAART. Event time was defined as time from commencing first‐line ART to either development of cholesterol level >6.5 mmol/L (254 mg/dL) or switch of first‐line therapy. The Kaplan–Meier product limit survival method was used to estimate time to abnormal cholesterol level, and the χ2 test was used for comparisons between drug classes. Cox's proportional hazards regression analysis was used to identify factors predicting a likelihood of raised cholesterol level.ResultsA total of 1664 patients were included in the study: 57.1% on two NRTIs+one NNRTI, 38.4% on two NRTIs+one PI, and 4.4% on two NRTIs+a boosted PI regimen. Regimens containing stavudine or PIs were associated with a significantly higher event risk and earlier time to event. No differences between efavirenz and nevirapine or between didanosine and lamivudine were observed. In 28 patients exposed to the combination of tenofovir+lamivudine+efavirenz, there were no episodes of elevated cholesterol level.ConclusionDyslipidaemia has emerged as an important issue in HIV‐infected individuals receiving antiretroviral therapy. This study demonstrates that age at start of therapy, baseline cholesterol level, stavudine use and PI use are all associated with increased risk of hypercholesterolemia on initial therapy. Both NRTI and NNRTI/PI choice influence risk of hypercholesterolaemia.
Drug‐resistance mutations in antiretroviral‐naïve patients with established HIV‐1 infection in Mexico
Authors: Escoto‐Delgadillo M , Vázquez‐Valls E , Ramírez‐Rodríguez M , Corona‐Nakamura A , Amaya‐Tapia G , Quintero‐Pérez N , Panduro‐Cerda A , Torres‐Mendoza BM 
Published: October 2005

ObjectivesTo describe the prevalence of baseline drug‐resistance mutations, resistance to antiretroviral drugs, and the subsequent virological response to therapy in treatment‐naïve patients from Mexico with established HIV‐1 infection.MethodsResistance testing was performed on plasma samples from antiretroviral‐naïve patients. Data on mutations associated with antiretroviral drug resistance were obtained using Stanford software (http://hivdb.stanford.edu).ResultsNinety‐six treatment‐naïve individuals were enrolled in the study during 2002–2003. Of these, 83 patients (86%) had at least one resistance mutation and 15 (16%) had drug resistance. At baseline, the mean plasma viral load was 299 834 HIV‐1 RNA copies/mL, and at follow‐up it was 37 620 copies/mL (P<0.0001). Primary mutations in the reverse transcriptase region were observed in 15% of patients. For nucleoside inhibitors, mutations T215Y/C and F77L (3%) and D67N/S, T69N and M184V (2%), were detected. For nonnucleoside inhibitors, mutations K103N/R (6%), Y181C (3%) and G190A (2%) were detected. Overall, 6% of patients showed resistance to delavirdine and nevirapine, 4% to efavirenz, and 2% to lamivudine and nelfinavir. Twelve patients showed no response to treatment and three of these patients had antiretroviral drug resistance.ConclusionsThe prevalence of baseline drug‐resistance mutations found in this study was similar to that found in previous reports for newly HIV‐infected individuals, although access to and management of antiretrovirals in Mexico are different.
Consensus Statements, Sample Statutory Provisions, and Model Regulations Regarding Driver Licensing and Epilepsy
Authors:   American Academy of Neurology, American Epilepsy Society, and Epilepsy Foundation of America
Published: October 2005

RéSUMé:Les representants de l'American Academy of Neurology, de l'American épilepsy Society et de l'épilepsy Foundation of America se sont reunies du 31 mai au 2 juin 1991, pour une conference de consensus sur les criteres appropries a l'attribution d'un permis de conduire chez les patients épileptiques. En utilisant des positions de consensus comme base de leur travail, ils ont mis au point des regulations types et des provisions stat‐utaires types, sur lesquelles ils se sont mis d'accord en mars 1992. Il y avait un consensus unanime, cependant, selon lequel des modifications évolutives de leur prise de position seraient vraisemblablement fondees sur l'experience et sur l'emergence de données nouvelles et plus précises. Les decisions d'autorisa‐tion de conduite devraient are faites par l'autorite gouvernementale appropriie plutôt que par le médecintraitant. Cette autorite gouvernementale devrait bénéficier d'une commission médicale consultative ou similaire, qui devrait inclure au moins un membre ayant une experience dans le traitement de l'épilepsie et des troubles episodiques de la conscience ou des fonctions motrices. Les médecins devraient bénéficier d'une immunite pour leur choix de signaler ou de ne pas signaler un patient a cette autorite. Aux Etats Unis, il y a eu un consensus selon lequel les statuts des differents états devraient etablir la structure du processus d'autorisation a la conduite, ainsi que les droits d'appel et donner au departement des vehicules a nioteur l'autorite, ainsi qu'une protection adequate contre les poursuites aux personnes impli‐quées dans ce processus. Des criteres médicaux pour le permis de conduire semblent devoir and préferentiellement etablis sous la forme de regulations ou de conseils medicaux, plutôt que d'étre fixts au niveau legidatif.
Interaction Between Two Quantitative Trait Loci Affects Fetal Haemoglobin Expression
Authors: Garner C. , Menzel S. , Martin C. , Silver N. , Best S. , Spector T. D. , Thein S. L. 
Published: October 2005

SummaryThe biological mechanisms controlling complex quantitative traits are likely to be affected by interactions between genetic factors, sometimes referred to as epistasis. The identification of interacting loci through genetic analyse faces many challenges, and few examples of replicated findings of interaction exist for humans and model system organisms. The replication of an interaction, or the non‐independence, of two quantitative trait loci (QTL) affecting the developmental switch from the expression of fetal to adult haemoglobin is reported here. Fetal haemoglobin expression in adults is a highly heritable, yet complex, phenotype. Using a sample of 874 dizygotic twin pairs of European descent, we found linkage to a QTL on chromosome 8 to be conditional on the twin pairs' genotypes at a polymorphism in the β‐globin complex; an interaction originally identified in a large Asian Indian kindred. The β‐globin polymorphism has been previously shown to be associated with fetal haemoglobin levels in adults. This study reports the first known replication of a genetic interaction between QTLs influencing a complex human trait.
The Association of Mitochondrial DNA 5178 C > A Polymorphism with Plasma Lipid Levels Among Three Ethnic Groups
Authors: Lal S. , Madhavan M. , Heng C. K. 
Published: October 2005

SummaryMitochondria are eukaryotic cytoplasmic organelles responsible for oxidative phosphorylation. The C to A nucleotide transversion in the NADH dehydrogenase subunit 2 (MT‐ND2) coding region of mitochondrial DNA has been reported to be associated with plasma lipid levels, adult onset diseases and longevity. We have examined the role of this polymorphism in relation to plasma lipid levels and age in a total of 713 healthy individuals belonging to 3 ethnic groups in Singapore. The frequency of the A allele was significantly higher (p < 0.05) among the Chinese (0.15) in comparison to the Malays (0.05) and Indians (0.02). No significant difference in the frequency of the allele was observed between healthy and coronary artery disease subjects, and between age‐stratified subjects. We found that the polymorphism is significantly associated in an ethnic‐ and gender‐specific manner with plasma apoB levels in the Chinese males (p < 0.05). This is the first epidemiological report of the mt5178 C > A polymorphism and its association with plasma lipid levels in Asian populations outside Japan.
SNP Selection for Association Studies: Maximizing Power across SNP Choice and Study Size
Authors: Pardi F. , Lewis C. M. , Whittaker J. C. 
Published: October 2005

SummarySelection of single nucleotide polymorphisms (SNPs) is a problem of primary importance in association studies and several approaches have been proposed. However, none provides a satisfying answer to the problem of how many SNPs should be selected, and how this should depend on the pattern of linkage disequilibrium (LD) in the region under consideration. Moreover, SNP selection is usually considered as independent from deciding the sample size of the study. However, when resources are limited there is a tradeoff between the study size and the number of SNPs to genotype. We show that tuning the SNP density to the LD pattern can be achieved by looking for the best solution to this tradeoff. Our approach consists of formulating SNP selection as an optimization problem: the objective is to maximize the power of the final association study, whilst keeping the total costs below a given budget. We also propose two alternative algorithms for the solution of this optimization problem: a genetic algorithm and a hill climbing search. These standard techniques efficiently find good solutions, even when the number of possible SNPs to choose from is large. We compare the performance of these two algorithms on different chromosomal regions and show that, as expected, the selected SNPs reflect the LD pattern: the optimal SNP density varies dramatically between chromosomal regions.
The Significant Increase in Cardiovascular Disease Risk in APOEɛ4 Carriers is Evident Only in Men Who Smoke: Potential Relationship Between Reduced Antioxidant Status and ApoE4
Authors: Talmud P. J. , Stephens J. W. , Hawe E. , Demissie S. , Cupples L. A. , Hurel S. J. , Humphries S. E. , Ordovas J. M. 
Published: October 2005

SummaryData from 1668 men (316 cardiovascular disease events) from the Framingham Offspring Study was reanalysed, specifically examining APOE:smoking interactions. Overall hazard ratio (HR) for smoking was 1.95 (1.52, 2.50) compared to non‐smokers. Using ɛ3/3 as a referent group, in non‐smokers HRs for ɛ2 carriers (ɛ2+; 1.04 (0.61, 1.76) and ɛ4 carriers (ɛ4+; 1.04 (0.70, 1.54) showed no major risk increase. In smokers, HRs were 1.96 (1.26, 2.78) in ɛ3ɛ3 men, 3.46 (2.14, 5.60; p = 0.09 for interaction) in ɛ2+ and 3.81 (2.49, 5.84; p = 0.01 for interaction), with a significant interaction between daily cigarette consumption and APOE genotype on risk (p = 0.03). The potential mechanism for this APOEɛ4:smoking interaction was examined in a second study of 728 Caucasian patients with diabetes, where markers of reactive oxygen species were available. APOE genotype was not associated with plasma OX‐LDL or total antioxidant status (TAOS) in non‐smokers. However, in smokers ɛ4+ had 26.7% higher plasma OX‐LDL than other genotypes (APOE:smoking interaction p = 0.04), while ɛ2+ had 28.4% higher plasma TAOS than ɛ3ɛ3 and ɛ4+ combined (APOE:smoking interaction p = 0.026). Although direct extrapolation needs to be considered with caution, these results identify that the cardiovascular disease risk‐raising effect of ɛ4+ is confined to smokers, and a feasible mechanism is presented by the reduced antioxidant capacity/increased OX‐LDL of apoE4.
Assessment of the Role of Genetic Polymorphism in Venous Thrombosis Through Artificial Neural Networks
Authors: Penco S. , Grossi E. , Cheng S. , Intraligi M. , Maurelli G. , Patrosso M. C. , Marocchi A. , Buscema M. 
Published: October 2005

Summary Purpose: To assess the role of genetic polymorphisms in venous thrombosis events (VTE) using Artificial Neural Networks (ANNs), a model for solving non‐linear problems frequently associated with complex biological systems, due to interactions between biological, genetic and environmental factors. Methods: A database was generated from a case‐control study of venous thrombosis, using 238 patients and 211 controls. The database of 64 variables included age, gender and a panel of 62 genetic variants. Three different ANNs were compared, with logistic regression for the accuracy of predicting cases and controls Results: ANNs yielded a better performance than the logistic regression algorithm. Indeed, through ANNs models, the 62 variables related to genetic variants were first reduced to a set of 9, and then of 3 (MTHFR 677 C/T, FV arg506gln, ICAM1 gly214arg). Conclusions: The findings of this study illustrate the power of ANN in evaluating multifactorial data, and show that the different sensitivities of the models of elaboration are related to the characteristics of the data. This may contribute to a better understanding of the role played by genetic polymorphisms in VTE, and help to define, if possible, a test panel of genetic variants to estimate an individual's probability of developing the disease.
Characteristics and Outcomes of Older Adults with Community‐Acquired Pneumococcal Bacteremia
Authors: Chi Ru‐Chien , Jackson Lisa A. , Neuzil Kathleen M. 
Published: October 2005

Objectives: To describe baseline characteristics and clinical outcomes of older adults with pneumococcal bacteremia, compare the frequency of serious outcomes according to pneumococcal vaccination status, and assess factors associated with mortality.Design: Population‐based case‐series.Setting: Group Health Cooperative, a health maintenance organization in Washington State.Participants: Community‐dwelling adults aged 65 and older with a first episode of pneumococcal bacteremia between 1988 and 2002.Measurements: Demographic characteristics, underlying medical conditions, vaccination status, and clinical outcomes, including death, hospitalization, length of hospital stay, and postdischarge care, were assessed using chart review.Results: The mean age of the 200 elderly patients with pneumococcal bacteremia was 78; 61% were female. Forty percent had had chart‐documented pneumococcal vaccination before the onset of bacteremia. The spectrum of clinical severity and consequences was broad. Ten percent were treated as outpatients. Of the 90% who were hospitalized, 16% were admitted to the intensive care unit. All‐cause mortality at 30 days was 11%. Of survivors, 23% were discharged with home services, and another 20% were discharged to a nursing home. After controlling for age, sex, and pneumococcal vaccination status, predictors of death included coronary artery disease (odds ratio (OR)=4.6, 95% confidence interval (CI)=1.4–14.5) and immunocompromising conditions (OR=5.0, 95% CI=1.6–15.7). Outcomes were similar in patients who did and did not receive pneumococcal vaccination.Conclusion: In this elderly group, pneumococcal bacteremia was associated with substantial morbidity, mortality, and loss of independence. Coronary artery disease and immunocompromising conditions were independent predictors of death.
The Mechanism of Atrial Antiarrhythmic Action of RSD1235
Authors: FEDIDA DAVID , ORTH PETER M.R. , CHEN JANET Y.C. , LIN SHUNPING , PLOUVIER BERTRAND , JUNG GRACE , EZRIN ALAN M. , BEATCH GREGORY N. 
Published: October 2005

Introduction: RSD1235 is a novel drug recently shown to convert AF rapidly and safely in patients.1 Its mechanism of action has been investigated in a rat model of ischemic arrhythmia, along with changes in action potential (AP) morphology in isolated rat ventricular myocytes and effects on cloned channels. Methods and Results: Ischemic arrhythmias were inhibited with an ED50 of 1.5 μmol/kg/min, and repolarization times increased with non‐significant effects on PR and QRS durations. AP prolongation was observed in rat myocytes at low doses, with plateau elevation and a reduction in the AP overshoot at higher doses. RSD1235 showed selectivity for voltage‐gated K+ channels with IC50 values of 13 μM on hKv1.5 (1 Hz) versus 38 and 30 μM on Kv4.2 and Kv4.3, respectively, and 21 μM on hERG channels. RSD1235 did not block IK1 (IC50 > 1 mM) nor ICa,L (IC50= 220 μM) at 1 Hz in guinea pig ventricular myocytes (n = 4–5). The drug displayed mild (IC50= 43 μM at 1 Hz) open‐channel blockade of Nav1.5 with rapid recovery kinetics after rate reduction (10→1 Hz, 75% recovery with τ= 320 msec). Nav1.5 blocking potency increased with stimulus frequency from an IC50= 40 μM at 0.25 Hz, to an IC50= 9 μM at 20 Hz, and with depolarization increasing from 107 μM at −120 mV to 31 μM at −60 mV (1 Hz). Conclusions: These data suggest that RSD1235's clinical selectivity and AF conversion efficacy result from block of potassium channels combined with frequency‐ and voltage‐dependent block of INa.
POLICY AND INTERVENTION CONSIDERATIONS OF A NETWORK ANALYSIS OF STREET GANGS*
Authors: MCGLOIN JEAN MARIE 
Published: October 2005

Research Summary:This study details a network analysis of the street gang landscape in Newark, New Jersey. Using individual gang members as the unit of analysis and multiple layers of associations as the linkages within the networks, the results suggest that the gangs in Newark are loosely organized with pockets of cohesion. In addition, there is variation with regard to individual connectedness within the gangs, and certain gang members emerge as “cut‐points” or the only connection among gang members or groups of gang members.Policy Implications:The results lend further credence to the notion that problem analysis should precede gang interventions. In particular, the findings suggest that particular groups of gang members may be amenable to the collective accountability tactic, whereas others may become more cohesive as a consequence. Indeed, an intervention focused on individuals may be more productive in Newark. The cut‐points within gangs are particularly worthy of attention, both for their capacity to act as communication agents for a deterrence message and for their potential vulnerability to the pulling levers strategy.
An Algorithmic Strategy for Automated Generation of Multicomponent Software Tools for Virtual Manufacturing
Authors: Bless Patrick N. , Kapoor Shiv G. , DeVor Richard E. , Klabjan Diego 
Published: October 2005

Abstract
This paper describes an algorithmic strategy to facilitate the generation of multicomponent software tools for computer-aided manufacturing (CAM) and virtual manufacturing (VM). Components that are often used to build CAM and VM applications include a wide range of domain-specific knowledge sources and also more general utility components with often very heterogeneous characteristics. The identification of a suitable and compatible set of these components is the first and arguably most important step during the development process of any CAM or VM application. This paper presents an algorithmic strategy that automates this development step by solving a time-expanded network problem, referred to as the component set identification (CSI) problem. A definition of the CSI problem, a mathematical formulation, a solution procedure, and some computational results are presented. Finally, an application to predict hole quality in drilling is used to illustrate the functionality of the proposed algorithmic strategy.
Phonotactic Knowledge and Lexical-Semantic Processing in One-year-olds: Brain Responses to Words and Nonsense Words in Picture Contexts
Authors: Friedrich Manuela , Friederici Angela D. 
Published: October 2005

Abstract
During their first year of life, infants not only acquire probabilistic knowledge about the phonetic, prosodic, and phonotactic organization of their native language, but also begin to establish first lexical-semantic representations. The present study investigated the sensitivity to phonotactic regularities and its impact on semantic processing in 1-year-olds. We applied the method of event-related brain potentials to 12-and 19-month-old children and to an adult control group. While looking at pictures of known objects, subjects listened to spoken nonsense words that were phonotactically legal (pseudowords) or had phonotactically illegal word onsets (nonwords), or to real words that were either congruous or incongruous to the picture contents. In 19-month-olds and in adults, incongruous words and pseudowords, but not non-words, elicited an N400 known to reflect mechanisms of semantic integration. For congruous words, the N400 was attenuated by semantic priming. In contrast, 12-month-olds did not show an N400 difference, neither between pseudo-and nonwords nor between incongruous and congruous words. Both 1-year-old groups and adults additionally displayed a lexical priming effect for congruous words, that is, a negativity starting around 100 msec after words onset. One-year-olds, moreover, displayed a phonotactic familiarity effect, that is, a widely distributed negativity starting around 250 msec in 19-month-olds but occurring later in 12-month-olds. The results imply that both lexical priming and phonotactic familiarity already affect the processing of acoustic stimuli in children at 12 months of age. In 19-month-olds, adult-like mechanisms of semantic integration are present in response to phonotactically legal, but not to phonotactically illegal, nonsense words, indicating that children at this age treat pseudo-words, but not nonwords, as potential word candidates.
When Blue is Larger than Red: Colors Influence Numerical Cognition in Synesthesia
Authors: Kadosh Roi Cohen , Sagiv Noam , Linden David E. J. , Robertson Lynn C. , Elinger Gali , Henik Avishai 
Published: October 2005

Abstract
In synesthesia, certain stimuli (“inducers”) may give rise to perceptual experience in additional modalities not normally associated with them (“concurrent”). For example, color-grapheme synesthetes automatically perceive achromatic numbers as colored (e.g., 7 is turquoise). Although synesthetes know when a given color matches the one evoked by a certain number, colors do not automatically give rise to any sort of number experience. The behavioral consequences of synesthesia have been documented using Stroop-like paradigms, usually using color judgments. Owing to the unidirectional nature of the synesthetic experience, little has been done to obtain performance measures that could indicate whether bidirectional cross-activation occurs in synesthesia. Here it is shown that colors do implicitly evoke numerical magnitudes in color-grapheme synesthetes, but not in nonsynesthetic participants. It is proposed that bidirectional co-activation of brain areas is responsible for the links between color and magnitude processing in color-grapheme synesthesia and that unidirectional models of synesthesia might have to be revised.