A non-variational approach to nonlinear stability in stellar dynamics applied to the King model

In previous work by Y. Guo and G. Rein, nonlinear stability of equilibria in stellar dynamics, i.e., of steady states of the Vlasov-Poisson system, was accessed by variational techniques. Here we propose a different, non-variational technique and use it to prove nonlinear stability of the King model against a class of spherically symmetric, dynamically accessible perturbations. This model is very important in astrophysics and was out of reach of the previous techniques

Apolipoprotein E epsilon 4 (APOE-ε4) genotype is associated with decreased 6-month verbal memory performance after mild traumatic brain injury

Introduction: The apolipoprotein E (APOE) ε4 allele associates with memory impairment in neurodegenerative diseases. Its association with memory after mild traumatic brain injury (mTBI) is unclear. Methods: mTBI patients (Glasgow Coma Scale score 13–15, no neurosurgical intervention, extracranial Abbreviated Injury Scale score ≤1) aged ≥18 years with APOE genotyping results were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study. Cohorts determined by APOE-ε4(+/−) were assessed for associations with 6-month verbal memory, measured by California Verbal Learning Test, Second Edition (CVLT-II) subscales: Immediate Recall Trials 1–5 (IRT), Short-Delay Free Recall (SDFR), Short-Delay Cued Recall (SDCR), Long-Delay F

Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of l

Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium.

Development Psychopathology in context: famil

Association of Forced Vital Capacity with the Developmental Gene NCOR2

Background Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes. Methods Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 children (ALSPAC). Associations were considered replicated if the replication p-value survived Bonferroni correction (p<0.002; 0.05/25), with a nominal p-value considered as suggestive evidence. For SNPs with evidence of replication, effects on the expression levels of nearby genes in lung tissue were tested in 1,111 lung samples (Lung eQTL consortium), with further functional investigation performed using public epigenomic profiling data (ENCODE). Results NCOR2-rs12708369 showed strong replication in children (p = 0.0002), with replication unavailable in adults due to low imputation quality. This intronic variant is in a strong transcriptional enhancer element in lung fibroblasts, but its eQTL effects could not be tested due to low imputation quality in the eQTL dataset. SERPINE2-rs6754561 replicated at nominal level in both adults (p = 0.036) and children (p = 0.045), while WNT16-rs2707469 replicated at nominal level only in adults (p = 0.026). The eQTL analyses showed association of WNT16-rs2707469 with expression levels of the nearby gene CPED1.We found no statistically significant eQTL effects for SERPINE2-rs6754561. Conclusions We have identified a new gene, NCOR2, in the retinoic acid signalling pathway pointing to a role of Vitamin A metabolism in the regulation of FVC. Our findings also support SERPINE2, a COPD gene with weak previous evidence of association with FVC, and suggest WNT16 as a further promising candidate

Diagnosis and Management of Systemic Endemic Mycoses Causing Pulmonary Disease

Systemic endemic mycoses cause high rates of morbidity and mortality in certain regions of the world and the real impact on global health is not well understood. Diagnosis and management remain challenging, especially in low-prevalence settings, where disease awareness is lacking. The main challenges include the variability of clinical presentation, the fastidious and slow-growing nature of the fungal pathogens, the paucity of diagnostic tests, and the lack of options and toxicity of antifungal drugs. Coccidioidomycosis and paracoccidioidomycosis are restricted to the Americas only, and while histoplasmosis and blastomycosis also occur predominantly in the Americas, these mycoses have also been reported on other continents, especially in sub-Saharan Africa. Talaromycosis is endemic in tropical and subtropical regions in South-East Asia and southern China. Systemic endemic mycoses causing pulmonary disease are usually acquired via the airborne route by inhalation of fungal spores. Infections can range from asymptomatic or mild with flu-like illnesses to severe pulmonary or disseminated diseases. Skin involvement is frequent in patients with paracoccidioidomycosis, blastomycosis, sporotrichosis, and talaromycosis and manifests as localized lesions or diffuse nodules in disseminated disease, but can also occur with other endemic mycoses. Culture and/or characteristic histopathology from clinical samples is the diagnostic standard for endemic mycoses. Immunological assays are often not available for the diagnosis of most endemic mycoses and molecular amplification methods for the detection of fungal nucleic acids are not standardized at present. The first-line treatment for mild to moderate histoplasmosis, paracoccidioidomycosis, blastomycosis, sporotrichosis, and talaromycosis is itraconazole. Severe illness is treated with amphotericin B. Patients with severe coccidioidomycosis should receive fluconazole. Treatment duration depends on the specific endemic mycosis, the severity of disease, and the immune status of the patient, ranging between 6 weeks and lifelong treatment. (C) 2018 S. Karger AG, Base

Prevalence and determinants of virological failure in HIV-infected children on antiretroviral therapy in rural Cameroon: a cross-sectional study

Item does not contain fulltextBACKGROUND: In Africa, success of antiretroviral treatment (ART) seems to lag behind in children compared with adults, and high therapeutic failure rates have been reported. We aimed to identify prevalence and determinants of virological failure in HIV-infected children treated under programmatic conditions. METHODS: All patients 200 copies/ml). Among children on nevirapine (NVP), plasma levels were subtherapeutic in 14.2% and supratherapeutic in 42.2%. Determinants of virological failure included male sex, lower CD4(+) T-cell counts, subtherapeutic drug levels, longer time on ART and a deceased mother. Poor adherence was associated with subtherapeutic NVP plasma levels and advanced disease stages (WHO stage 3/4). CONCLUSIONS: This study demonstrates high virological failure rates and a high variability of NVP plasma levels among HIV-infected children in a routine ART programme in rural Cameroon. Strategies to improve adherence to ART in HIV-infected children are urgently needed