Assessing the psychosocial consequences of epilepsy: a community-based study.

BACKGROUND: Few studies have measured, using validated scales, the psychosocial handicap of epilepsy in a general practice setting. AIM: To assess the prevalence of psychosocial problems associated with epilepsy. METHOD: A survey was undertaken of 309 subjects, with one or more non-febrile epileptic seizures, drawn from two general practices in the United Kingdom (UK). The outcome measures were the Subjective Handicap of Epilepsy Scale (SHE), the SF-36, and the Hospital Anxiety and Depression scale (HAD). RESULTS: One-third of persons with active epilepsy were significantly handicapped by their condition. The severity of subjective handicap was related to seizure frequency and to the duration of remission of seizures. Between one-third and one-half of subjects scored as 'cases' on the HAD scale and on the mental health subscale of the SF-36. Only one-third of the psychiatric morbidity revealed by the questionnaires had been recognized by the general practitioner (GP). Scores on the SF-36 indicated that people with active seizures perceived themselves as significantly less healthy than those in remission, and that, for persons in remission, drug treatment had a detrimental effect on certain aspects of well-being. CONCLUSIONS: The occurrence of seizures, even at low frequencies, is associated with psychosocial handicap, and this may remain covert in general practice.     

Web‐Based Experiments for the Study of Collective Social Dynamics in Cultural Markets

Social scientists are often interested in understanding how the dynamics of social systems are driven by the behavior of individuals that make up those systems. However, this process is hindered by the difficulty of experimentally studying how individual behavioral tendencies lead to collective social dynamics in large groups of people interacting over time. In this study, we investigate the role of social influence, a process well studied at the individual level, on the puzzling nature of success for cultural products such as books, movies, and music. Using a “multiple‐worlds” experimental design, we are able to isolate the causal effect of an individual‐level mechanism on collective social outcomes. We employ this design in a Web‐based experiment in which 2,930 participants listened to, rated, and downloaded 48 songs by up‐and‐coming bands. Surprisingly, despite relatively large differences in the demographics, behavior, and preferences of participants, the experimental results at both the individual and collective levels were similar to those found in Salganik, Dodds, and Watts (2006) . Further, by comparing results from two distinct pools of participants, we are able to gain new insights into the role of individual behavior on collective outcomes. We conclude with a discussion of the strengths and weaknesses of Web‐based experiments to address questions of collective social dynamics.     

Bayes Estimates of Haplotype Effects

We describe a Markov chain Monte Carlo implementation of a Bayesian approach to estimating associations of a trait with a large set of haplotypes recently introduced by Clayton and Jones [Am J Hum Genet 65:1161–9, 2000]. The model uses the length of the longest segment in common between any two haplotypes to define the prior correlation structure for the set of haplotype effects, using an intrinsic autocorrelation model. When applied to the Genetic Analysis Workshop 12 data for trait Q1, we found highly significant variation between haplotypes, using either a structured or unstructured covariance matrix. © 2001 Wiley‐Liss, Inc.     

Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass.

Several genome-wide scans have been performed to detect loci that regulate BMD, but these have yielded inconsistent results, with limited replication of linkage peaks in different studies. In an effort to improve statistical power for detection of these loci, we performed a meta-analysis of genome-wide scans in which spine or hip BMD were studied. Evidence was gained to suggest that several chromosomal loci regulate BMD in a site-specific and sex-specific manner. INTRODUCTION: BMD is a heritable trait and an important predictor of osteoporotic fracture risk. Several genome-wide scans have been performed in an attempt to detect loci that regulate BMD, but there has been limited replication of linkage peaks between studies. In an attempt to resolve these inconsistencies, we conducted a collaborative meta-analysis of genome-wide linkage scans in which femoral neck BMD (FN-BMD) or lumbar spine BMD (LS-BMD) had been studied. MATERIALS AND METHODS: Data were accumulated from nine genome-wide scans involving 11,842 subjects. Data were analyzed separately for LS-BMD and FN-BMD and by sex. For each study, genomic bins of 30 cM were defined and ranked according to the maximum LOD score they contained. While various densitometers were used in different studies, the ranking approach that we used means that the results are not confounded by the fact that different measurement devices were used. Significance for high average rank and heterogeneity was obtained through Monte Carlo testing. RESULTS: For LS-BMD, the quantitative trait locus (QTL) with greatest significance was on chromosome 1p13.3-q23.3 (p = 0.004), but this exhibited high heterogeneity and the effect was specific for women. Other significant LS-BMD QTLs were on chromosomes 12q24.31-qter, 3p25.3-p22.1, 11p12-q13.3, and 1q32-q42.3, including one on 18p11-q12.3 that had not been detected by individual studies. For FN-BMD, the strongest QTL was on chromosome 9q31.1-q33.3 (p = 0.002). Other significant QTLs were identified on chromosomes 17p12-q21.33, 14q13.1-q24.1, 9q21.32-q31.1, and 5q14.3-q23.2. There was no correlation in average ranks of bins between men and women and the loci that regulated BMD in men and women and at different sites were largely distinct. CONCLUSIONS: This large-scale meta-analysis provided evidence for replication of several QTLs identified in previous studies and also identified a QTL on chromosome 18p11-q12.3, which had not been detected by individual studies. However, despite the large sample size, none of the individual loci identified reached genome-wide significance.     

Ventilatory effects of clonidine alone and in the presence of alfentanil, in human volunteers.

Clonidine, an alpha 2-adrenergic agonist, can potentiate opioid-induced analgesia. In a double-blind placebo-controlled study in human volunteers, we sought to determine whether clonidine also potentiates opioid-induced respiratory depression. Hypercapnic ventilatory responses (minute ventilation, mean inspiratory flow rate, and mouth occlusion pressure) were measured in five healthy male volunteers on two separate occasions (with or without clonidine, approximately 3.5 micrograms.kg-1 orally) under the following conditions: baseline, 2 h after clonidine/placebo (alfentanil concentration of 0), and during computer-controlled alfentanil infusions to approximate plasma concentrations of 5, 10, 20, 40, and 80 ng.ml-1. Plasma alfentanil concentrations were measured before and after each rebreathing test, and clonidine concentrations were measured after each rebreathing test. The end-tidal CO2 (PET(CO2)) was measured continuously. Data were analyzed by repeated-measures analysis of variance. The PET(CO2) and measured concentrations of alfentanil were included as covariates, and a compound symmetry error analysis was assumed. Statistical significance was achieved when P less than 0.05. For minute ventilation, mean inspiratory flow rate, and mouth occlusion pressure there was a statistically significant relationship to the covariates of PET(CO2) and plasma alfentanil concentration. Clonidine, when compared to placebo, caused a small but significant depression of mean inspiratory flow rate. There was similarly a small, but statistically insignificant, depression of minute ventilation by clonidine. The mouth occlusion pressure was not affected by clonidine treatment. Clonidine treatment did not potentiate alfentanil-induced respiratory depression. Although the combination of an opioid and an alpha 2-adrenergic agonist may act synergistically for the analgesic response, there is no synergistic effect by this drug combination on respiratory depression.     

Variation in HLA-associated risks of childhood insulin-dependent diabetes in the finnish population: I. Allele effects at A,B, and DR Loci

Variation in the risk of insulin-dependent diabetes mellitus (IDDM) across alleles at HLA-A, B, and DR loci was investigated in a population-based study of 801 families of children with newly diagnosed IDDM in Finland nationwide. Parallel analyses assessed the relative frequencies of alleles in IDDM children compared with age-matched sibling controls and with the four possible genotypes which could have been inherited from the parents. The joint effects of DR3 and DR4 alleles were investigated under dominant, recessive, and additive models of gene expression. The additive model gave the best fit, though the relative risk for DR4 homozygotes was smaller than predicted. To investigate other alleles, we fitted the standard multiplicative model for alleles at each locus. After controlling for the correlation among alleles, significantly elevated risks were found for B13, DR3, DR4, and DR14. Subjects with these alleles have more than twice the risk of IDDM as those without. Alleles A24 and B62 incurred relative risks between one and two. DR2 and DR5 were significantly negatively associated with IDDM, incurring less than half the risk. These findings support an independent role of class I antigens in the etiology of IDDM. © 1995 Wiley-Liss, Inc.     

Suppression of Natural Killer Cell Activity by Ethanol Consumption and Food Restriction

Effects of 4-week food restriction and ethanol consumption on natural killer (NK) cell activity and carcass composition were evaluated. Female, C57BL/6 mice given water (H2O) or ethanol (20% w/v, ETOH) ad libitum were placed in one of three dietary groups: unrestricted (UNR), moderately restricted (MR, 2.2 g/day), or severely restricted (SR, 1.8 g/day). Food restriction alone (MR, SR) significantly reduced body, spleen, and thymus weights; carcass lipid content (SR only); spleen cell number; and baseline and interleukin-2 (rIL-2) stimulated NK cell activities. Ethanol consumption was unaffected by food restriction and in restricted mice it did not suppress food intake. Thus, average calories derived from ethanol increased from 30% (UNR) to 40% (SR) with the degree of food restriction in these groups. Mice given ethanol and restricted food intake had at least as heavy or heavier body, spleen, and thymus weights than water-drinking (H2O) counterparts. Spleen cell number was reduced in ethanol-consuming (ETOH), food restricted groups compared with UNR H2O control. Baseline NK cell activity was suppressed 50% to 90% in all ETOH and food-restricted groups. rIL-2 stimulated NK cell activity was suppressed 18% to 76% in food restricted mice independent of ethanol intake. These results indicate that supplementary ethanol calories did not enhance NK cell activity in UNR ETOH mice, nor did they protect splenic NK cell activity from the suppressant effects of food restriction. Ethanol consumption significantly increased carcass lipid content in all groups compared with their H2O counterparts. This increase was largely responsible for the preservation of body weight in ETOH mice especially during food restriction.