Despite a century of research on complex traits in humans, the relative importance and specific nature of the influences of genes and environment on human traits remain controversial. We report a ...meta-analysis of twin correlations and reported variance components for 17,804 traits from 2,748 publications including 14,558,903 partly dependent twin pairs, virtually all published twin studies of complex traits. Estimates of heritability cluster strongly within functional domains, and across all traits the reported heritability is 49%. For a majority (69%) of traits, the observed twin correlations are consistent with a simple and parsimonious model where twin resemblance is solely due to additive genetic variation. The data are inconsistent with substantial influences from shared environment or non-additive genetic variation. This study provides the most comprehensive analysis of the causes of individual differences in human traits thus far and will guide future gene-mapping efforts. All the results can be visualized using the MaTCH webtool.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Disturbed circadian rhythm is a potentially modifiable cause of delirium among patients in intensive-care units (ICUs). Bright-light therapy in the daytime can realign circadian rhythm and reduce the ...incidence of delirium. We investigated whether a high-intensity dynamic light application (DLA) would reduce ICU-acquired delirium.
This was a randomised, controlled, single-centre trial of medical and surgical patients admitted to the ICU of a teaching hospital in the Netherlands. Patients older than 18 years, expected to stay in the ICU longer than 24 h and who could be assessed for delirium were randomised to DLA or normal lighting (control), according to a computer-generated schedule. The DLA was administered through ceiling-mounted fluorescent tubes that delivered bluish-white light up to 1700 lux between 0900 h and 1600 h, except for 1130-1330 h, when the light was dimmed to 300 lux. The light could only be turned off centrally by investigators. Control light levels were 300 lux and lights could be turned on and off from inside the room. The primary endpoint was the cumulative incidence of ICU-acquired delirium. Analyses were by intention to treat and per protocol. The study was terminated prematurely after an interim analysis for futility. This study is registered with Clinicaltrials.gov, number NCT01274819.
Between July 1, 2011, and Sept 9, 2013, 734 patients were enrolled, 361 in the DLA group and 373 in the control group. Delirium occurred in 137 (38%) of 361 DLA patients and 123 (33%) of 373 control patients (odds ratio 1·24, 95% CI 0·92-1·68, p=0·16). No adverse events were noted in patients or staff.
DLA as a single intervention does not reduce the cumulative incidence of delirium. Bright-light therapy should be assessed as part of a multicomponent strategy.
None.
Mercaptopurine, a thiopurine, is used in various disorders of immune regulation, such as autoimmune hepatitis. Thiopurine metabolism is complex with risk for overdosing, especially when metabolism is ...impaired by liver dysfunction. Hepatotoxicity may be due to mercaptopurine overdose and is often reversible after prompt cessation of the drug.
Treatment of thiopurine toxicity is mainly supportive and literature on enhanced elimination by renal replacement therapy is ambiguous.
In this case of thiopurine toxicity, a patient with autoimmune hepatitis presents with abdominal pain, nausea, vomiting, and diarrhea. We show in this case report that renal replacement therapy had no effect on total body clearance of mercaptopurine.
After a decade of genome-wide association studies (GWASs), fundamental questions in human genetics, such as the extent of pleiotropy across the genome and variation in genetic architecture across ...traits, are still unanswered. The current availability of hundreds of GWASs provides a unique opportunity to address these questions. We systematically analyzed 4,155 publicly available GWASs. For a subset of well-powered GWASs on 558 traits, we provide an extensive overview of pleiotropy and genetic architecture. We show that trait-associated loci cover more than half of the genome, and 90% of these overlap with loci from multiple traits. We find that potential causal variants are enriched in coding and flanking regions, as well as in regulatory elements, and show variation in polygenicity and discoverability of traits. Our results provide insights into how genetic variation contributes to trait variation. All GWAS results can be queried and visualized at the GWAS ATLAS resource ( https://atlas.ctglab.nl ).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
During the COVID-19 pandemic in the Netherlands, governmental regulations resulted in a lockdown for adults as well as children/adolescents. Schools were closed and contact with other people ...was limited. In this cross-sectional, population-based study, we aimed to investigate the mental/social health of children/adolescents during COVID-19 lockdown.
Methods
Two representative samples of Dutch children/adolescents (8–18 years) before COVID-19 (2018,
N
= 2401) and during lockdown (April 2020,
N
= 844) were compared on the Patient-Reported Outcomes Measurement Information System (PROMIS) domains: global health, peer relationships, anxiety, depressive symptoms, anger, sleep-related impairment by linear mixed models and calculating relative risks (RR (95% CI)) for the proportion of severe scores. Variables associated with worse mental/social health during COVID-19 were explored through multivariable regression models. The impact of COVID-19 regulations on the daily life of children was qualitatively analyzed.
Results
Participants reported worse PROMIS
T
-scores on all domains during COVID-19 lockdown compared to before (absolute mean difference range 2.1–7.1 (95% CI 1.3–7.9). During lockdown, more children reported severe Anxiety (RR = 1.95 (1.55–2.46) and Sleep-Related Impairment (RR = 1.89 (1.29–2.78) and fewer children reported poor Global Health (RR = 0.36 (0.20–0.65)). Associated factors with worse mental/social health were single-parent family, ≥ three children in the family, negative change in work situation of parents due to COVID-19 regulations, and a relative/friend infected with COVID-19. A large majority (> 90%) reported a negative impact of the COVID-19 regulations on daily life.
Conclusion
This study showed that governmental regulations regarding lockdown pose a serious mental/social health threat on children/adolescents that should be brought to the forefront of political decision-making and mental healthcare policy, intervention, and prevention.
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CEKLJ, DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
In the present paper, we evaluate determination of circulating anodic (CAA) and cathodic (CCA) antigen for the diagnosis of an active
Schistosoma infection in humans, in comparison to the diagnostic ...performance of parasitological examination and the demonstration of specific antibodies. Illustrated by three different studies, which all deal with the diagnosis of either recent or low intensity infections, we further discuss our experiences with these diagnostic methods. For the diagnosis of recent infections, specific antibody determination showed to be very sensitive, particularly in individuals originating from non-endemic areas. For the assessment of cure and for the diagnosis of active infections in endemic areas, the methods of choice are parasitological examination and CAA or CCA determination. Depending on infection levels of the target population and on logistic conditions, CAA and CCA determination may either replace parasitological examination or, in the case of light infections, may be used as a complementary diagnostic tool.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Introduction
Vulvar lichen sclerosus (VLS) occurs in at least one in 900 girls. There is limited knowledge as to what extent the disease persists in adulthood and what the repercussions in adulthood ...may be. The aim of this study is to evaluate the long‐term consequences of VLS diagnosed in childhood or adolescence.
Material and methods
The population of females histologically diagnosed with VLS in childhood or adolescence in the Netherlands between 1991 and 2015 was identified through the national pathology database. Histological specimens were retrieved and re‐evaluated. Potential participants for whom the diagnosis was reconfirmed and who are now adults, were then traced and surveyed. Descriptive statistics were calculated and compared with the literature. Main outcome measures are the demographics of the cohort, their scores on standardized quality of life (QoL) and sexuality questionnaires and answers to additional questions regarding patients’ experience with the disease. The questionnaires used were the Dermatology Life Quality Index (DLQI), the Skindex‐29, the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale‐Revised (FSDS‐R). Secondary outcome measures include obstetric history and histological features found in the original tissue specimens.
Results
A total of 81 women participated, median age 29.0 years, median follow‐up from childhood diagnosis 19.5 years. Both QoL and sexuality were somewhat affected in 51.9% of cases. Less than half (45%) reported having regular check‐ups. Forty‐five (56%) reported symptoms within the past year; of those with symptoms, 14 (31%) were not under surveillance. Cesarean section rate (14.5%) was comparable to the general population, and there were more high‐grade obstetric anal sphincter injuries with vaginal deliveries than expected. Sixteen respondents (20%) were not aware of the childhood diagnosis prior to this study.
Conclusions
Symptoms due to VLS are reported by most adults diagnosed as juveniles. QoL and sexuality are affected and correlate to recent symptoms. VLS as a juvenile does not preclude a vaginal delivery. Women diagnosed with VLS in childhood or adolescence are often lost to follow‐up.
Vulvar lichen sclerosus (VLS), a chronic vulvar condition with symptoms including itching, pain and bleeding and often leading to permanent loss of vulvar skin and shape, is one of the most frequent diagnosis in girls who have vulvar complaints, affecting at least one in every 900 girls. VLS in children usually does not resolve at puberty, contrary to earlier beliefs. This study demonstrates what patients following a diagnosis of VLS in childhood and adolescence may experience as they reach adulthood.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A central paradigm in life-history theory is the trade-off between offspring number and quality. Several studies have investigated this trade-off in humans, but data are inconclusive, perhaps because ...prosperous socio-cultural factors mask the trade-off. Therefore, we studied 2461 offspring groups in an area under adverse conditions in northern Ghana with high fertility and mortality rates. In a linear mixed model controlling for differences in age and tribe of the mother and socioeconomic status, each additional child in the offspring group resulted in a 2.3% (95% CI 1.9-2.6%, P < 0.001) lower proportional survival of the offspring. Furthermore, we made use of the polygamous population structure and compared offspring of co-wives in 388 households, thus controlling for variation in resources between compounds. Here, offspring survival decreased 2.8% (95% CI 2.3-4.0%, P < 0.001) for each increase in offspring number. We interpret these data as an apparent quality-quantity trade-off in human offspring.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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