Modelling spectral and timing properties of accreting black holes: the hybrid hot flow paradigm

The general picture that emerged by the end of 1990s from a large set of optical and X-ray, spectral and timing data was that the X-rays are produced in the innermost hot part of the accretion flow, while the optical/infrared (OIR) emission is mainly produced by the irradiated outer thin accretion disc. Recent multiwavelength observations of Galactic black hole transients show that the situation is not so simple. Fast variability in the OIR band, OIR excesses above the thermal emission and a complicated interplay between the X-ray and the OIR light curves imply that the OIR emitting region is much more compact. One of the popular hypotheses is that the jet contributes to the OIR emission and even is responsible for the bulk of the X-rays. However, this scenario is largely ad hoc and is in contradiction with many previously established facts. Alternatively, the hot accretion flow, known to be consistent with the X-ray spectral and timing data, is also a viable candidate to produce the OIR radiation. The hot-flow scenario naturally explains the power-law like OIR spectra, fast OIR variability and its complex relation to the X-rays if the hot flow contains non-thermal electrons (even in energetically negligible quantities), which are required by the presence of the MeV tail in Cyg X-1. The presence of non-thermal electrons also lowers the equilibrium electron temperature in the hot flow model to <100 keV, making it more consistent with observations. Here we argue that any viable model should simultaneously explain a large set of spectral and timing data and show that the hybrid (thermal/non-thermal) hot flow model satisfies most of the constraints.Comment: 26 pages, 13 figures. To be published in the Space Science Reviews and as hard cover in the Space Sciences Series of ISSI - The Physics of Accretion on to Black Holes (Springer Publisher

Serodiagnosis of strongyloidiasis. The application and significance

Parasitological diagnosis based on the faecal examination is frequently difficult in cases of chronic, low-level S. stercoralis infection. Even when a newly developed sensitive method (an agar plate culture) is applied, it is essential to examine faecal samples repeatedly to achieve a correct diagnosis. Additionally, it is important to note that a negative result does not necessarily indicate the unequivocal absence of the infection. On the other hand, several serological tests which have recently been developed for strongyloidiasis have proven reliable when used to complement parasitological examination. We have developed two serological tests, ELISA and GPAT, to demonstrate Strongyloides infection and possible applications of the serological tests for diagnosis, mass-screening, epidemiological study and postchemotherapy evaluation of strongyloidiasis were reviewed based on our recent studies.O diagnóstico parasitológico baseado no exame de fezes é muitas vezes difícil, principalmente nos casos de infecções crônicas ou leves pelo S. stercoralis. Mesmo utilizando o mais novo e sensível método (cultura em placas de ágar) é essencial examinar repetidamente as amostras fecais, para um diagnóstico correto. É importante ressaltar também que o resultado negativo não indica de modo inequívoco a ausência da infecção. Por outro lado, vários testes sorológicos recentemente desenvolvidos para estrongiloidíase tem provado a sua eficácia quando usados para complementar exames parasitológicos. Para demonstrar infecção por Strongyloides desenvolvemos dois tipos de testes sorológicos - ELISA e GPAT - e, com base em nossos recentes estudos, apresentamos uma opinião sobre sua possível aplicação para screening em massa, estudos epidemiológicos e avaliação pós-tratamento de estrongiloidíases

First report of Strongyloides sp. (Nematoda, Strongyloididae) in Lutreolina crassicaudata (Didelphimorphia: Didelphidae)

Abstract The present study reports the first case of the presence of the intestinal nematode Strongyloides sp. in fecal examinations of a male Lutreolina crassicaudata, considered a synanthropic marsupial species with zoonotic potential. The Willis technique was used for the diagnosis. Presence of typical eggs of Strongyloides species in feces was detected. A fecal culture was performed to obtain larval stages, free-living adults and infective third stage larvae (L3) of this nematode after seven days, which was morphologically identified as Strongyloididae. This is the first report of infection by Strongyloides sp. in a tick-tailed opossum from Brazil

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD

Genetic loci associated with prevalent and incident myocardial infarction and coronary heart disease in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

Background Genome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome. Methods and results Using samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both crosssectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and allcause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12

New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475,000 Individuals

Background - Genome-wide association studies have recently identified &gt;400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association. Methods and Results - Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ≈475 000), and the other in the subset of individuals of European descent (≈423 000). Twenty-one SNVs were genome-wide significant (P&lt;5×10-8) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency &lt;0.01, (rs3025380 at DBH) was genome-wide significant. Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk

Field prevalence and laboratory susceptibility of southern Australian land snails to

Brachylaima cribbi is a terrestrial trematode of birds and mammals with helic id and hygromild land snails reported as first and second Intermediate hosts. However, reports describing the first Intermediate host range of B. cribbi have been limited to those snail species present In a small number of geographical locations In South Australia. The natural first Intermediate host range, distribution and prevalence of B. cribbi In land snails In southern Australia were determined. A total of 6,432 introduced and native land snails were collected from eight geographical districts across 3,000 km of southern Australia and examined microscopically for B. cribbi sporocysts. Four Introduced European snails, Theba pisana, Cernuella virgata, Cochlicella acuta and Cochlicella barbara were natural first Intermediate hosts. Sporocyst-infected snails were detected In all districts from Victoria to the west coast of South Australia, a distance of over 1,300 km. Natural sporocyst infection was not observed in introduced European snails Microxeromagna armillata and Helix aspersa or In native Australian land snails Succinea australis and Strangesta gawleri. Egg feeding experiments in the laboratory with B. cribbi confirmed the susceptibility of those species of snails found to be natural first intermediate hosts. Of those species not found to be Infected In nature, only M. armillata could be Infected In the laboratory. Although this study has shown that five different species of European land snails are suitable first Intermediate hosts for B. cribbi there are as yet no reports of B. cribbi from these snails In Europe or from other countries where they have been introduced. Further Investigations are needed in Europe to clarify the origins of this parasite

Kinetics of Cells in the Intestinal Mucosa of Mice following Oral Infection with &lt;i&gt;Ancylostoma ceylanicum&lt;/i&gt;

A variety of cell types in the intestinal mucosa of mice has been observed following oral infection with &lt;i&gt;Ancylostoma ceylanicum &lt;/i&gt;and the changes in their numbers quantified. The number of lamina propria mast cells increased following infection and reached a peak at 4 days; by 21 days the numbers had returned to normal levels. Globule leucocytes displayed a similar marked response but the numbers returned to within normal limits 7 days after infection. Granular intraepithelial lymphocytes did not alter significantly during the period of observation whereas non-granular intraepithelial lymphocytes declined in numbers following infection and were significantly decreased by 3 weeks. Goblets cells showed a similar response to infection as lamina propria mast cells and reached a peak level at 4 days. Following initial fluctuations in eosinophil numbers there was a substantial increase in the numbers of these cells with peak levels being reached at 21 days; eosinophil numbers then remained elevated for the duration of observation. Partial villous atrophy was seen 4 days after the arrival of larvae in the small intestine with maximum reduction in the length of villi at 7 days. Thereafter, there was a return to normal length followed by a significant elongation in villus length 28 days after infection. The influences of these various cell types on the expulsion of intestinal parasites are discussed.</jats:p