94 research outputs found
Genome-wide association study in an admixed case series reveals IL12A as a new candidate in Behçet Disease
Introduction: The etiology of Behçet's disease (BD) is unknown, but widely considered an excessive T-cell mediated inflammatory response in a genetically susceptible host. Recent genomewide association studies (GWAS) have shown limited number of novel loci-associations. The rarity and unequal distribution of the disease prevalence amongst different ethnic backgrounds have hampered the use of GWAS in cohorts of mixed ethnicity and sufficient sample size. However, novel statistical approaches have now enabled GWAS in admixed cohorts. Methods: We ran a GWAS on 336 BD cases and 5,843 controls. The cases consisted of Western Europeans, Middle Eastern and Turkish individuals. Participants from the Generation R study, a multiethnic birth cohort in Rotterdam, The Netherlands were used as controls. All samples were genotyped and data was combined. Linear regression models were corrected for population stratification using Genomic Principal Components and Linear Mixed Modelling. Meta-analysis was performed on selected results previously published. Results: We identified SNPs associated at genome-wide significant level mapping to the 6p21.33 (HLA) region. In addition to this known signal two potential novel associations on chromosomes 6 and 18 were identified, yet with low minor allele frequencies. Extended metaanalysis reveal a GWS association with the IL12A variant rs17810546 on chromosome 3. Discussion: We demonstrate that new statistical techniques enable GWAS analyses in a limited sized cohort of mixed ethnicity. After implementation, we confirmed the central role of the HLA region in the disease and identified new regions of interest. Moreover, we validated the association of a variant in the IL2A gene by meta-analysis with previous work. These findings enhance our
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Structure Loaded Vacuum Laser-Driven Particle Acceleration Experiments at SLAC
We present an overview of the future laser-driven particle acceleration experiments. These will be carried out at the E163 facility at SLAC. Our objectives include a reconfirmation of the proof-of-principle experiment, a staged buncher laser-accelerator experiment, and longer-term future experiments that employ dielectric laser-accelerator microstructures
The Kinetics of Primary Alpha Plate Growth in Titanium Alloys
The kinetics of primary alpha-Ti colony/Widmanstatten plate growth from the
beta are examined, comparing model to experiment. The plate growth velocity
depends sensitively both on the diffusivity D(T) of the rate-limiting species
and on the supersaturation around the growing plate. These result in a maxima
in growth velocity around 40 K below the transus, once sufficient
supersaturation is available to drive plate growth. In Ti-6246, the plate
growth velocity was found to be around 0.32 um min-1 at 850 oC, which was in
good agreement with the model prediction of 0.36 um min-1 . The solute field
around the growing plates, and the plate thickness, was found to be quite
variable, due to the intergrowth of plates and soft impingement. This solute
field was found to extend to up to 30 nm, and the interface concentration in
the beta was found to be around 6.4 at.% Mo. It was found that increasing O
content will have minimal effect on the plate lengths expected during
continuous cooling; in contrast, Mo approximately doubles the plate lengths
obtained for every 2 wt.% Mo reduction. Alloys using V as the beta stabiliser
instead of Mo are expected to have much faster plate growth kinetics at
nominally equivalent V contents. These findings will provide a useful tool for
the integrated design of alloys and process routes to achieve tailored
microstructures.Comment: Revised version resubmitted to journa
Health Care Utilization During the COVID-19 Pandemic Among Individuals Born Preterm
Importance: Limited data exist on pediatric health care utilization during the COVID-19 pandemic among children and young adults born preterm. Objective: To investigate differences in health care use related to COVID-19 concerns during the pandemic among children and young adults born preterm vs those born at term. Design, Setting, and Participants: In this cohort study, questionnaires regarding COVID-19 and health care utilization were completed by 1691 mother-offspring pairs from 42 pediatric cohorts in the National Institutes of Health Environmental Influences on Child Health Outcomes Program. Children and young adults (ages 1-18 years) in these analyses were born between 2003 and 2021. Data were recorded by the August 31, 2021, data-lock date and were analyzed between October 2021 and October 2022. Exposures: Premature birth (<37 weeks' gestation). Main Outcomes and Measures: The main outcome was health care utilization related to COVID-19 concerns (hospitalization, in-person clinic or emergency department visit, phone or telehealth evaluations). Individuals born preterm vs term (â„37 weeks' gestation) and differences among preterm subgroups of individuals (<28 weeks', 28-36 weeks' vs â„37 weeks' gestation) were assessed. Generalized estimating equations assessed population odds for health care used and related symptoms, controlling for maternal age, education, and psychiatric disorder; offspring history of bronchopulmonary dysplasia (BPD) or asthma; and timing and age at COVID-19 questionnaire completion. Results: Data from 1691 children and young adults were analyzed; among 270 individuals born preterm, the mean (SD) age at survey completion was 8.8 (4.4) years, 151 (55.9%) were male, and 193 (71.5%) had a history of BPD or asthma diagnosis. Among 1421 comparison individuals with term birth, the mean (SD) age at survey completion was 8.4 (2.4) years, 749 (52.7%) were male, and 233 (16.4%) had a history of BPD or asthma. Preterm subgroups included 159 individuals (58.5%) born at less than 28 weeks' gestation. In adjusted analyses, individuals born preterm had a significantly higher odds of health care utilization related to COVID-19 concerns (adjusted odds ratio [aOR], 1.70; 95% CI, 1.21-2.38) compared with term-born individuals; similar differences were also seen for the subgroup of individuals born at less than 28 weeks' gestation (aOR, 2.15; 95% CI, 1.40-3.29). Maternal history of a psychiatric disorder was a significant covariate associated with health care utilization for all individuals (aOR, 1.44; 95% CI, 1.17-1.78). Conclusions and Relevance: These findings suggest that during the COVID-19 pandemic, children and young adults born preterm were more likely to have used health care related to COVID-19 concerns compared with their term-born peers, independent of a history of BPD or asthma. Further exploration of factors associated with COVID-19-related health care use may facilitate refinement of care models
A Compact Dication Source for Ba Tagging and Heavy Metal Ion Sensor Development
We present a tunable metal ion beam that delivers controllable ion currents
in the picoamp range for testing of dry-phase ion sensors. Ion beams are formed
by sequential atomic evaporation and single or multiple electron impact
ionization, followed by acceleration into a sensing region. Controllability of
the ionic charge state is achieved through tuning of electrode potentials that
influence the retention time in the ionization region. Barium, lead, and cobalt
samples have been used to test the system, with ion currents identified and
quantified using a quadrupole mass analyzer. Realization of a clean
ion beam within a bench-top system represents an important
technical advance toward the development and characterization of barium tagging
systems for neutrinoless double beta decay searches in xenon gas. This system
also provides a testbed for investigation of novel ion sensing methodologies
for environmental assay applications, with dication beams of Pb and
Cd also demonstrated for this purpose
Predictors of retinochoroiditis in children with congenital toxoplasmosis : European, prospective cohort study
OBJECTIVE. By school age, 20% of children infected with congenital toxoplasmosis will have > 1 retinochoroidal lesion. We determined which children are most at risk and whether prenatal treatment reduces the risk of retinochoroiditis to help clinicians decide about treatment and follow-up. PATIENTS AND METHODS. We prospectively studied a cohort of children with congenital toxoplasmosis identified by prenatal or neonatal screening in 6 European countries. We determined the effects of prenatal treatment and prognostic markers soon after birth on the age at first detection of retinochoroiditis. RESULTS. Of 281 children with congenital toxoplasmosis, 50 developed ocular disease, and 17 had recurrent retinochoroiditis during a median follow-up of 4.1 years. Prenatal treatment had no significant effect on the age at first or subsequent lesions. Delayed start of postnatal treatment did not increase retinochoroiditis, but the analysis lacked power. Older gestational age at maternal seroconversion was weakly associated with a reduced risk of retinochoroiditis. The presence of nonocular clinical manifestations of congenital toxoplasmosis at birth strongly predicted retinochoroiditis. For 92% (230 of 249) of children with no retinochoroiditis detected before 4 months of age, the probability of retinochoroiditis by 4 years was low, whether clinical manifestations were present or not 8.0%. CONCLUSIONS. Prenatal treatment did not significantly reduce the risk of retinochoroiditis in this European cohort. If children have no retinochoroiditis in early infancy, the low risk of subsequent ocular disease may not justify postnatal treatment and repeated ophthalmic assessments during childhood. Controlled trials are needed to address the lack of evidence for the effectiveness of postnatal treatment
Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study
Background
The association of fitness with cancer risk is not clear.
Methods
We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (Nâ=â72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method.
Results
After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5âml O2â
minâ1â
kgâ1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HRâ=â0.81, 95% CI: 0.73â0.89), colorectal (0.94, 0.90â0.99), and breast cancer (0.96, 0.92â0.99). In MR analyses, a 0.5âSD increase in genetically predicted O2â
minâ1â
kgâ1 fat-free mass was associated with a lower risk of breast cancer (ORâ=â0.92, 95% CI: 0.86â0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated.
Discussion
Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention
Treating Ocular Toxoplasmosis - Current Evidence
The current treatment of ocular toxoplasmosis is controversial. The
mainstay of treatment has been pyrimethamine and sulphonamides with or
without systemic corticosteroids, but the actual evidence that
antibiotics have a beneficial effect in recurrent toxoplasmic
retinochoroiditis is unsupported by randomised placebo controlled
trials. Thus far there have only been three studies looking at the
efficacy of antibiotic treatment, all of which were methodologically
weak and two of which were perfomed more than 30 years ago. All studies
reported adverse effects from treatment. There is an urgent need for
further randomised, double blind, placebo controlled studies for
lesions in all parts of the retina and to test the efficacy of
adjunctive corticosteroid treatment
Effect of Zn concentration and grain size on prismatic slip in Mg-Zn binary alloys
Mg-Zn binary alloys with concentrations between 0 and 2.8wt% Zn have been prepared and processed via hot rolling and annealing to produce specimens with a strong basal texture and a range of grain sizes. These have been deformed in tension, a condition in which the deformation is dominated by prismatic slip. This data has been used to assess the Hall-Petch parameter as a function of Zn concentration for deformation dominated by prismatic slip. Pure magnesium showed non-linear Hall-Petch behaviour at large grain sizes, and this is compared to the values for prismatic slip measured on single crystals. The differences between critical resolved shear stress measurements made through single crystal, polycrystal and mathematical modelling techniques are also discussed
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