167 research outputs found

    Erythrocyte acid phosphatase phenotype and gestational length: no relationship in a sample of 3001 births

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    Erythrocyte acid phosphatase (ACP1) phenotype was examined in 3001 Caucasian infants born at the University of Michigan Women's Hospital. Contrary to reports from other studies, there was no relationship between the ACP1 phenotype and risk of preterm birth in either the total sample or when the sample was subdivided by sex of infant.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27696/1/0000082.pd

    Nature, Nurture, and the Meaning of Educational Attainment: Differences by Sex and Socioeconomic Status

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    Estimated heritability of educational attainment (EA) varies widely, from 23% to 80%, with growing evidence suggesting the degree to which genetic variation contributes to individual differences in EA is highly dependent upon situational factors. We aimed to decompose EA into influences attributable to genetic propensity and to environmental context and their interplay, while considering influences of rearing household economic status (HES) and sex. We use the Project Talent Twin and Sibling Study, drawn from the population-representative cohort of high school students assessed in 1960 and followed through 2014, to ages 68−72. Data from 3552 twins and siblings from 1741 families were analyzed using multilevel regression and multiple group structural equation models. Individuals from less-advantaged backgrounds had lower EA and less variation. Genetic variance accounted for 51% of the total variance, but within women and men, 40% and 58% of the total variance respectively. Men had stable genetic variance on EA across all HES strata, whereas high HES women showed the same level of genetic influence as men, and lower HES women had constrained genetic influence on EA. Unexpectedly, middle HES women showed the largest constraints in genetic influence on EA. Shared family environment appears to make an outsized contribution to greater variability for women in this middle stratum and whether they pursue more EA. Implications are that without considering early life opportunity, genetic studies on education may mischaracterize sex differences because education reflects different degrees of genetic and environmental influences for women and men

    The Project Talent Twin and Sibling Study: Zygosity and New Data Collection

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    The Project Talent Twin and Sibling (PTTS) study includes 4481 multiples and their 522 nontwin siblings from 2233 families. The sample was drawn from Project Talent, a U.S. national longitudinal study of 377,000 individuals born 1942–1946, first assessed in 1960 and representative of U.S. students in secondary school (Grades 9–12). In addition to the twins and triplets, the 1960 dataset includes 84,000 siblings from 40,000 other families. This design is both genetically informative and unique in facilitating separation of the ‘common’ environment into three sources of variation: shared by all siblings within a family, specific to twin-pairs, and associated with school/community-level factors. We term this the GIFTS model for genetics, individual, family, twin, and school sources of variance. In our article published in a previous Twin Research and Human Genetics special issue, we described data collections conducted with the full Project Talent sample during 1960–1974, methods for the recent linking of siblings within families, identification of twins, and the design of a 54-year follow-up of the PTTS sample, when participants were 68–72 years old. In the current article, we summarize participation and data available from this 2014 collection, describe our method for assigning zygosity using survey responses and yearbook photographs, illustrate the GIFTS model applied to 1960 vocabulary scores from more than 80,000 adolescent twins, siblings and schoolmates and summarize the next wave of PTTS data collection being conducted as part of the larger Project Talent Aging Study

    Lifetime comorbidities between social phobia and mood disorders in the U.S. National Comorbidity Survey

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    Background. General population data were used to study co-morbidities between lifetime social phobia and mood disorders. Methods. Data come from the US National Comorbidity Survey (NCS). Results. Strong associations exist between lifetime social phobia and major depressive disorder (odds ratio 2·9), dysthymia (2·7) and bipolar disorder (5·9). Odds ratios increase in magnitude with number of social fears. Reported age of onset is earlier for social phobia than mood disorders in the vast majority of co-morbid cases. Temporally-primary social phobia predicts subsequent onset of mood disorders, with population attributable risk proportions of 10–15%. Social phobia is also associated with severity and persistence of co-morbid mood disorders. Conclusions. Social phobia is a commonly occurring, chronic and seriously impairing disorder that is seldom treated unless it occurs in conjunction with another co-morbid condition. The adverse consequences of social phobia include increased risk of onset, severity and course of subsequent mood disorders. Early outreach and treatment of primary social phobia might not only reduce the prevalence of this disorder itself, but also the subsequent onset of mood disorders

    General Cognitive Ability in High School, Attained Education, Occupational Complexity, and Dementia Risk

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    INTRODUCTION We address the extent to which adolescent cognition predicts dementia risk in later life, mediated by educational attainment and occupational complexity. METHODS Using data from Project Talent Aging Study (PTAS), we fitted two structural equation models to test whether adolescent cognition predicts cognitive impairment (CI) and Ascertain Dementia 8 (AD8) status simultaneously (NCognitive Assessment = 2477) and AD8 alone (NQuestionnaire = 6491) 60 years later, mediated by education and occupational complexity. Co-twin control analysis examined 82 discordant pairs for CI/AD8. RESULTS Education partially mediated the effect of adolescent cognition on CI in the cognitive assessment aample and AD8 in the questionnaire sample (Ps \u3c 0.001). Within twin pairs, differences in adolescent cognition were small, but intrapair differences in education predicted CI status. DISCUSSION Adolescent cognition predicted dementia risk 60 years later, partially mediated through education. Educational attainment, but not occupational complexity, contributes to CI risk beyond its role as a mediator of adolescent cognition, further supported by the co-twin analyses

    HCV Induces Oxidative and ER Stress, and Sensitizes Infected Cells to Apoptosis in SCID/Alb-uPA Mice

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    Hepatitis C virus (HCV) is a blood-borne pathogen and a major cause of liver disease worldwide. Gene expression profiling was used to characterize the transcriptional response to HCV H77c infection. Evidence is presented for activation of innate antiviral signaling pathways as well as induction of lipid metabolism genes, which may contribute to oxidative stress. We also found that infection of chimeric SCID/Alb-uPA mice by HCV led to signs of hepatocyte damage and apoptosis, which in patients plays a role in activation of stellate cells, recruitment of macrophages, and the subsequent development of fibrosis. Infection of chimeric mice with HCV H77c also led an inflammatory response characterized by infiltration of monocytes and macrophages. There was increased apoptosis in HCV-infected human hepatocytes in H77c-infected mice but not in mice inoculated with a replication incompetent H77c mutant. Moreover, TUNEL reactivity was restricted to HCV-infected hepatocytes, but an increase in FAS expression was not. To gain insight into the factors contributing specific apoptosis of HCV infected cells, immunohistological and confocal microscopy using antibodies for key apoptotic mediators was done. We found that the ER chaperone BiP/GRP78 was increased in HCV-infected cells as was activated BAX, but the activator of ER stress–mediated apoptosis CHOP was not. We found that overall levels of NF-κB and BCL-xL were increased by infection; however, within an infected liver, comparison of infected cells to uninfected cells indicated both NF-κB and BCL-xL were decreased in HCV-infected cells. We conclude that HCV contributes to hepatocyte damage and apoptosis by inducing stress and pro-apoptotic BAX while preventing the induction of anti-apoptotic NF-κB and BCL-xL, thus sensitizing hepatocytes to apoptosis

    Prevalence and age of onset for drug use in seven international sites: Results from the international consortium of psychiatric epidemiology

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    This study compares lifetime prevalence and age of first use (onset) for alcohol, cannabis, and other drugs in six international sites. Data from seven epidemiologic field surveys that used compatible instruments and study designs were compiled for cross-site analyses by the International Consortium of Psychiatric Epidemiology (ICPE). The world health organization’s composite international diagnostic instrument (WHO-CIDI) and additional items were used to ascertain drug use in each site. Lifetime use rates were estimated for alcohol, cannabis, and other illicit drugs. Survival analyses were used to estimate age of onset. Study settings and main results: use of alcohol twelve or more times ranged in descending order from the Netherlands (86.3%), United States (71.7%), Ontario, Canada (71.6%); São Paulo, Brazil (66.1%), Munich, Germany (64.9%), Fresno, California (USA) (51.9%), to Mexico City (43.2%). Use of cannabis five or more times in a lifetime ranged from 28.8 in the United States to 1.7% in Mexico City, and other drugs ranged from United States (19.4%) to Mexico City (1.7%). Age of first use was similar across study sites. This study demonstrates the fundamental uniformity of onset patterns by age as contrasted with wide variations in lifetime prevalences across sites. Study findings suggest that drug use patterns may change among emigrating populations from low consumption nations as a consequence of international resettlement in nations with higher rates. Methodological limitations of the study along with recommendations for future international comparative research are discussed

    Recommendations for the analysis of individually randomised controlled trials with clustering in one arm - a case of continuous outcomes

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    BACKGROUND: In an individually randomised controlled trial where the treatment is delivered by a health professional it seems likely that the effectiveness of the treatment, independent of any treatment effect, could depend on the skill, training or even enthusiasm of the health professional delivering it. This may then lead to a potential clustering of the outcomes for patients treated by the same health professional, but similar clustering may not occur in the control arm. Using four case studies, we aim to provide practical guidance and recommendations for the analysis of trials with some element of clustering in one arm. METHODS: Five approaches to the analysis of outcomes from an individually randomised controlled trial with clustering in one arm are identified in the literature. Some of these methods are applied to four case studies of completed randomised controlled trials with clustering in one arm with sample sizes ranging from 56 to 539. Results are obtained using the statistical packages R and Stata and summarised using a forest plot. RESULTS: The intra-cluster correlation coefficient (ICC) for each of the case studies was small (<0.05) indicating little dependence on the outcomes related to cluster allocations. All models fitted produced similar results, including the simplest approach of ignoring clustering for the case studies considered. CONCLUSIONS: A partially clustered approach, modelling the clustering in just one arm, most accurately represents the trial design and provides valid results. Modelling homogeneous variances between the clustered and unclustered arm is adequate in scenarios similar to the case studies considered. We recommend treating each participant in the unclustered arm as a single cluster. This approach is simple to implement in R and Stata and is recommended for the analysis of trials with clustering in one arm only. However, the case studies considered had small ICC values, limiting the generalisability of these results

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
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