Characterization of the Specificity, Functionality, and Durability of Host TCell Responses Against the Full-Length Hepatitis E Virus

The interplay between host antiviral immunity and immunopathology during hepatitis E virus (HEV) infection determines important clinical outcomes. We characterized the specificity, functionality, and durability of host T-cell responses against the full-length HEV virus and assessed a novel “Quantiferon” assay for the rapid diagnosis of HEV infection. Eighty-nine volunteers were recruited from Oxford, Truro (UK), and Toulouse (France), including 44 immune-competent patients with acute HEV infection, 18 HEV-exposed immunosuppressed organ-transplant recipients (8 with chronic HEV), and27 healthy volunteers. A genotype 3a peptide library (616 overlapping peptides spanning open reading frames [ORFs] 1-3) was used in interferon-gamma (IFN-c) T-cell ELISpot assays. CD41/CD81 T-cell subsets and polyfunctionality were defined using ICCS and SPICE analysis. Quantification of IFN-c used whole-blood stimulation with recombinant HEVcapsid protein in the QuantiFERON kit. HEV-specific T-cell responses were detected in 41/44 immune-competent HEV exposed volunteers (median magnitude: 397 spot-forming units/106 peripheral blood mononuclear cells), most frequentlytargeting ORF2. High-magnitude, polyfunctional CD4 and CD81 T cells were detected during acute disease and maintained to 12 years, but these declined over time, with CD81 responses becoming more monofunctional. Low-level responses were detectable in immunosuppressed patients. Twenty-three novel HEV CD41 and CD81 T-cell targets were mapped predominantly to conserved genomic regions. QuantiFERON testing demonstrated an inverse correlation between IFN-c production and the time from clinical presentation, providing 100% specificity, and 71% sensitivity (area under the receiver operator characteristic curve of 0.86) for HEV exposure at 0.3 IU/mL. Conclusion: Robust HEV-specific T-cell responses generated during acute disease predominantly target ORF2, but decline in magnitude and polyfunctionality over time. Defining HEV T-cell targets will be important for the investigation of HEV-associated autoimmune disease. (HEPATOLOGY 2016; 00:000-000)

Respective impacts of Arctic sea ice decline and increasing greenhouse gases concentration on Sahel precipitation

The impact of climate change on Sahel precipitation is uncertain and has to be widely documented. Recently, it has been shown that Arctic sea ice loss leverages the global warming effects worldwide, suggesting a potential impact of Arctic sea ice decline on tropical regions. However, defining the specific roles of increasing greenhouse gases (GHG) concentration and declining Arctic sea ice extent on Sahel climate is not straightforward since the former impacts the latter. We avoid this dependency by analysing idealized experiments performed with the CNRM-CM5 coupled model. Results show that the increase in GHG concentration explains most of the Sahel precipitation change. We found that the impact due to Arctic sea ice loss depends on the level of atmospheric GHG concentration. When the GHG concentration is relatively low (values representative of 1980s), then the impact is moderate over the Sahel. However, when the concentration in GHG is levelled up, then Arctic sea ice loss leads to increased Sahel precipitation. In this particular case the ocean-land meridional gradient of temperature strengthens, allowing a more intense monsoon circulation. We linked the non-linearity of Arctic sea ice decline impact with differences in temperature and sea level pressure changes over the North Atlantic Ocean. We argue that the impact of the Arctic sea ice loss will become more relevant with time, in the context of climate change

Immersive bilingualism reshapes the core of the brain

Bilingualism has been shown to affect the structure of the brain, including cortical regions related to language. Less is known about subcortical structures, such as the basal ganglia, which underlie speech monitoring and language selection, processes that are crucial for bilinguals, as well as other linguistic functions, such as grammatical and phonological acquisition and processing. Simultaneous bilinguals have demonstrated significant reshaping of the basal ganglia and the thalamus compared to monolinguals. However, it is not clear whether these effects are due to learning of the second language (L2) at a very young age or simply due to continuous usage of two languages. Here, we show that bilingualism-induced subcortical effects are directly related to the amount of continuous L2 usage, or L2 immersion. We found significant subcortical reshaping in non-simultaneous (or sequential) bilinguals with extensive immersion in a bilingual environment, closely mirroring the recent findings in simultaneous bilinguals. Importantly, some of these effects were positively correlated to the amount of L2 immersion. Conversely, sequential bilinguals with comparable proficiency and age of acquisition (AoA) but limited immersion did not show similar effects. Our results provide structural evidence to suggestions that L2 acquisition continuously occurs in an immersive environment, and is expressed as dynamic reshaping of the core of the brain. These findings propose that second language learning in the brain is a dynamic procedure which depends on active and continuous L2 usage

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

The Contribution of Dental Amalgam to Urinary Mercury Excretion in Children

BACKGROUND: Urinary mercury concentrations are widely used as a measure of mercury exposure from dental amalgam fillings. No studies have evaluated the relationship of these measures in a longitudinal context in children. OBJECTIVE: We evaluated urinary mercury in children 8–18 years of age in relation to number of amalgam surfaces and time since placement over a 7-year course of amalgam treatment. METHODS: Five hundred seven children, 8–10 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of dental amalgam in children. Subjects were randomized to either dental amalgam or resin composite treatments. Urinary mercury and creatinine concentrations were measured at baseline and annually on all participants. RESULTS: Treatment groups were comparable in baseline urinary mercury concentration (~ 1.5 μg/L). Mean urinary mercury concentrations in the amalgam group increased to a peak of ~ 3.2 μg/L at year 2 and then declined to baseline levels by year 7 of follow-up. There was a strong, positive association between urinary mercury and both number of amalgam surfaces and time since placement. Girls had significantly higher mean urinary mercury concentrations than boys throughout the course of amalgam treatment. There were no differences by race in urinary mercury concentration associated with amalgam exposure. CONCLUSIONS: Urinary mercury concentrations are highly correlated with both number of amalgam fillings and time since placement in children. Girls excrete significantly higher concentrations of mercury in the urine than boys with comparable treatment, suggesting possible sex-related differences in mercury handling and susceptibility to mercury toxicity.info:eu-repo/semantics/publishedVersio

Urinary porphyrin excretion in normal children and adolescentes

Background—Urinary porphyrins are diagnostic of various metabolic disorders and xenobiotic exposures, but comprehensive normative data for urinary porphyrin concentrations in children are currently unavailable. Methods—Subjects were participants in a prospective, randomized, controlled clinical trial of dental materials safety, 8 to 12 y at inception, who were followed longitudinally for 7 y after baseline with an extensive battery of neurobehavioral, neurological, renal function and urinary porphyrin assessments. Porphyrins were quantified by HPLC. Linear regression analyses were used to measure associations of porphyrin levels with age and gender. Results—Mean concentrations, 95% confidence intervals, and 10th 50th, and 90th percentiles for all 5 typically excreted urinary porphyrins are presented by year of age and by gender. Unadjusted urinary concentrations (μg/l) of all 5 porphyrins remained relatively constant throughout the age range of 8–18 y for both males and females. In contrast, creatinine-adjusted urinary porphyrin concentrations (μg/g) declined significantly throughout this age range in both genders. Boys had significantly higher pentacarboxyl- and copro- porphyrin levels compared with girls both before and after creatinine adjustment. Conclusions—Normative longitudinal data provided herein may facilitate the clinical assessment of pediatric metabolic disorders and may be of particular relevance in evaluating porphyrin changes as a biological indicator of disease or xenobiotic exposures among children and adolescents.info:eu-repo/semantics/publishedVersio

Deciphering Lyman-α\alpha Emission Deep into the Epoch of Reionisation

A major event in cosmic history is the genesis of the first starlight in our Universe, ending the ''Dark Ages''. During this epoch, the earliest luminous sources were enshrouded in neutral and pristine gas, which was gradually ionised in a process called ''reionisation''. Hence, one of the brightest emission lines in star-forming galaxies, Lyman-$\alpha$ (Ly-$\alpha$), was predicted to emerge only towards the end of the epoch of reionisation, about one billion years after the Big Bang. However, this picture has been challenged over the past decade by the surprising detection of Ly-$\alpha$ in galaxies less than 500 million years old. Here we show, by taking advantage of both high-resolution and high-sensitivity images from the James Webb Space Telescope programs PRIMER, CEERS and FRESCO, that all galaxies in our sample of Ly-$\alpha$ emitters deep in the epoch of reionisation have close companions. To understand the physical processes that lead to the observed Ly-$\alpha$ emission in our sample, we take advantage of novel on-the-fly radiative transfer magnetohydrodynamical simulations with cosmic ray feedback. We find that in the early Universe, the rapid build up of mass through frequent galactic mergers leads to very bursty star formation which in turn drives episodes of high intrinsic Ly-$\alpha$ emission and facilitates the escape of Ly-$\alpha$ photons along channels cleared of neutral gas. These merging galaxies reside in clustered environments thus creating sufficiently large ionised bubbles. This presents a solution to the long-standing puzzle of the detection of Ly-$\alpha$ emission deep into the epoch of reionisation.Comment: Submitted to Nature. 38 pages, 9 figures, 2 table

Global no net loss of natural ecosystems

A global goal of no net loss of natural ecosystems or better has recently been proposed, but such a goal would require equitable translation to country-level contributions. Given the wide variation in ecosystem depletion, these could vary from net gain (for countries where restoration is needed), to managed net loss (in rare circumstances where natural ecosystems remain extensive and human development imperative is greatest). National contributions and international support for implementation also must consider non-area targets factors such as the capacity to conserve and the imperative for human development