A standardised sampling protocol for robust assessment of reach-scale fish community diversity in wadeable New Zealand streams

The New Zealand fish fauna contains species that are affected not only by river system connectivity, but also by catchment and local-scale changes in landcover, water quality and habitat quality. Consequently, native fish have potential as multi-scale bioindicators of human pressure on stream ecosystems, yet no standardised, repeatable and scientifically defensible methods currently exist for effectively quantifying their abundance or diversity in New Zealand stream reaches. Here we report on the testing of a back-pack electrofishing method, modified from that used by the United States Environmental Protection Agency, on a wide variety of wadeable stream reaches throughout New Zealand. Seventy-three first- to third-order stream reaches were fished with a single pass over 150-345 m length. Time taken to sample a reach using single-pass electrofishing ranged from 1-8 h. Species accumulation curves indicated that, irrespective of location, continuous sampling of 150 stream metres is required to accurately describe reach-scale fish species richness using this approach. Additional species detection beyond 150 m was rare (<10%) with a single additional species detected at only two out of the 17 reaches sampled beyond this distance. A positive relationship was also evident between species detection and area fished, although stream length rather than area appeared to be the better predictor. The method tested provides a standardised and repeatable approach for regional and/or national reporting on the state of New Zealand's freshwater fish communities and trends in richness and abundance over time

Impact of debris cover on glacier ablation and atmosphere - glacier feedbacks in the Karakoram

This work was partly carried out under the Collaborative Adaptation Research Initiative in Africa and Asia (CARIAA) with financial support from the UK Government’s Department for International Development and the International Development Research Centre, Ottawa, Canada.The Karakoram range of the Hindu-Kush Himalaya is characterized by both extensive glaciation and a widespread prevalence of surficial debris cover on the glaciers. Surface debris exerts a strong control on glacier surface-energy and mass fluxes and, by modifying surface boundary conditions, has the potential to alter atmosphere– glacier feedbacks. To date, the influence of debris on Karakoram glaciers has only been directly assessed by a small number of glaciological measurements over short periods. Here, we include supraglacial debris in a high-resolution, interactively coupled atmosphere–glacier modeling system. To investigate glaciological and meteorological changes that arise due to the presence of debris, we perform two simulations using the coupled model from 1 May to 1 October 2004: one that treats all glacier surfaces as debris-free and one that introduces a simplified specification for the debris thickness. The basin-averaged impact of debris is a reduction in ablation of 14 %, although the difference exceeds 5mw:e: on the lowest-altitude glacier tongues. The relatively modest reduction in basin-mean mass loss results in part from non-negligible sub-debris melt rates under thicker covers and from compensating increases in melt under thinner debris, and may help to explain the lack of distinct differences in recent elevation changes between clean and debriscovered ice. The presence of debris also strongly alters the surface boundary condition and thus heat exchanges with the atmosphere; near-surface meteorological fields at lower elevations and their vertical gradients; and the atmospheric boundary layer development. These findings are relevant for glacio-hydrological studies on debris-covered glaciers and contribute towards an improved understanding of glacier behavior in the Karakoram

Modeling hepatitis C micro-elimination among people who inject drugs with direct-acting antivirals in metropolitan Chicago

Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease and mortality worldwide. Direct-acting antiviral (DAA) therapy leads to high cure rates. However, persons who inject drugs (PWID) are at risk for reinfection after cure and may require multiple DAA treatments to reach the World Health Organization’s (WHO) goal of HCV elimination by 2030. Using an agent-based model (ABM) that accounts for the complex interplay of demographic factors, risk behaviors, social networks, and geographic location for HCV transmission among PWID, we examined the combination(s) of DAA enrollment (2.5%, 5%, 7.5%, 10%), adherence (60%, 70%, 80%, 90%) and frequency of DAA treatment courses needed to achieve the WHO’s goal of reducing incident chronic infections by 90% by 2030 among a large population of PWID from Chicago, IL and surrounding suburbs. We also estimated the economic DAA costs associated with each scenario. Our results indicate that a DAA treatment rate of >7.5% per year with 90% adherence results in 75% of enrolled PWID requiring only a single DAA course; however 19% would require 2 courses, 5%, 3 courses and <2%, 4 courses, with an overall DAA cost of $325 million to achieve the WHO goal in metropolitan Chicago. We estimate a 28% increase in the overall DAA cost under low adherence (70%) compared to high adherence (90%). Our modeling results have important public health implications for HCV elimination among U.S. PWID. Using a range of feasible treatment enrollment and adherence rates, we report robust findings supporting the need to address re-exposure and reinfection among PWID to reduce HCV incidence

The EXPRES Stellar Signals Project II. State of the Field in Disentangling Photospheric Velocities

Measured spectral shifts due to intrinsic stellar variability (e.g., pulsations, granulation) and activity (e.g., spots, plages) are the largest source of error for extreme-precision radial-velocity (EPRV) exoplanet detection. Several methods are designed to disentangle stellar signals from true center-of-mass shifts due to planets. The Extreme-precision Spectrograph (EXPRES) Stellar Signals Project (ESSP) presents a self-consistent comparison of 22 different methods tested on the same extreme-precision spectroscopic data from EXPRES. Methods derived new activity indicators, constructed models for mapping an indicator to the needed radial-velocity (RV) correction, or separated out shape- and shift-driven RV components. Since no ground truth is known when using real data, relative method performance is assessed using the total and nightly scatter of returned RVs and agreement between the results of different methods. Nearly all submitted methods return a lower RV rms than classic linear decorrelation, but no method is yet consistently reducing the RV rms to sub-meter-per-second levels. There is a concerning lack of agreement between the RVs returned by different methods. These results suggest that continued progress in this field necessitates increased interpretability of methods, high-cadence data to capture stellar signals at all timescales, and continued tests like the ESSP using consistent data sets with more advanced metrics for method performance. Future comparisons should make use of various well-characterized data sets—such as solar data or data with known injected planetary and/or stellar signals—to better understand method performance and whether planetary signals are preserved

A hot mini-Neptune and a temperate, highly eccentric sub-Saturn around the bright K-dwarf TOI-2134

Funding: ACC and TGW acknowledge support from STFC consolidated grant numbers ST/R000824/1 and ST/V000861/1, and UKSA grant number ST/R003203/1. RDH is funded by the UK Science and Technology Facilities Council (STFC)’s Ernest Rutherford Fellowship (grant no. ST/V004735/1). SD is funded by the UK Science and Technology Facilities Council (grant no. ST/V004735/1). BSL is funded by a UK Science and Technology Facilities Council (STFC) studentship (ST/V506679/1). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement SCORE no. 851555).We present the characterisation of an inner mini-Neptune in a 9.2292005±0.0000063 day orbit and an outer mono-transiting sub-Saturn planet in a 95.50+0.36-0.25 day orbit around the moderately active, bright (mv = 8.9 mag) K5V star TOI-2134. Based on our analysis of five sectors of TESS data, we determine the radii of TOI-2134b and c to be 2.69±0.16 R⊕ for the inner planet and 7.27±0.42 R⊕ for the outer one. We acquired 111 radial-velocity spectra with HARPS-N and 108 radial-velocity spectra with SOPHIE. After careful periodogram analysis, we derive masses for both planets via Gaussian Process regression: 9.13+0.78-0.76 M⊕ for TOI-2134b and 41.89+7.69-7.83 M⊕ for TOI-2134c. We analysed the photometric and radial-velocity data first separately, then jointly. The inner planet is a mini-Neptune with density consistent with either a water-world or a rocky core planet with a low-mass H/He envelope. The outer planet has a bulk density similar to Saturn’s. The outer planet is derived to have a significant eccentricity of 0.67+0.05-0.06 from a combination of photometry and RVs. We compute the irradiation of TOI-2134c as 1.45±0.10 times the bolometric flux received by Earth, positioning it for part of its orbit in the habitable zone of its system. We recommend further RV observations to fully constrain the orbit of TOI-2134c. With an expected Rossiter-McLaughlin (RM) effect amplitude of 7.2±1.3 m-1, we recommend TOI-2134c for follow-up RM analysis to study the spin-orbit architecture of the system. We calculate the Transmission Spectroscopy Metric, and both planets are suitable for bright-mode NIRCam atmospheric characterisation.Publisher PDFPeer reviewe

Structure and immunogenicity of alternative forms of the simian immunodeficiency virus gag protein expressed using Venezuelan equine encephalitis virus replicon particles

Venezuelan equine encephalitis virus replicon particles (VRP) were engineered to express different forms of SIV Gag to compare expression in vitro, formation of intra- and extracellular structures and induction of humoral and cellular immunity in mice. The three forms examined were full-length myristylated SIV Gag (Gagmyr+), full-length Gag lacking the myristylation signal (Gagmyr-), or a truncated form of Gagmyr- comprising only the matrix and capsid domains (MA/CA). Comparison of VRP-infected primary mouse embryo fibroblasts, mouse L929 cells and primate Vero cells showed comparable expression levels for each protein, as well as extracellular virus-like particles (VRP-Gagmyr+), and distinctive cytoplasmic aggregates (VRP-Gagmyr-) with each cell type. VPR were used to immunize BALB/c mice, and immune responses were compared using an interferon (IFN)-γ ELISPOT assay and a serum antibody ELISA. Although all three VRP generated similar levels of IFN-γ-producing cells at 1 week post-boost, at 10 weeks post-boost the MA/CA-VRP-induced response was maintained at a significantly higher level relative to that induced by Gagmyr+-VRP. Antibody responses to MA/CA-VRP and Gagmyr+-VRP were not significantly different

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe