Ostreid herpesvirus 1 detection and relationship with Crassostrea gigas spat mortality in France between 1998 and 2006

Since its molecular characterisation, Ostreid herpesvirus 1 (OsHV-1) has been regularly detected in Crassostrea gigas in France. Although its pathogenicity was demonstrated on larval stages, its involvement during mortality outbreaks at the juvenile stage was highly suspected but not evidenced. To investigate mortality outbreaks, the French National Network for Surveillance and Monitoring of Mollusc Health (REPAMO) carried out two surveys in juvenile C. gigas. The first survey lasted from 1998 to 2006 and was an epidemiological inquiry occurring when oyster farmers reported mortality outbreaks. The second survey, a longitudinal one, was set up in 1998 to complete the network observations on OsHV-1. Data analysis showed a specific pattern of mortality outbreaks associated with OsHV-1 detection. Ostreid herpesvirus 1 detection mainly appeared during the summer, suggesting the influence of the seawater temperature on its occurrence. It mostly presented a patchy distribution in the field in contrast to the nursery. Significant relationship between OsHV-1 detection and spat mortality was found, preferentially in sheltered and closed environments. The longitudinal survey confirmed most of the network observations. Although subsequent works particularly epidemiological surveys would be useful to confirm the causal link between the detection of OsHV-1 and the mortality outbreaks in juvenile C. gigas, the role of OsHV-1 in oyster mortality is progressing

Heat stored in the Earth system:where does the energy go?

Human-induced atmospheric composition changes cause a radiative imbalance at the top of the atmosphere which is driving global warming. This Earth energy imbalance (EEI) is the most critical number defining the prospects for continued global warming and climate change. Understanding the heat gain of the Earth system – and particularly how much and where the heat is distributed – is fundamental to understanding how this affects warming ocean, atmosphere and land; rising surface temperature; sea level; and loss of grounded and floating ice, which are fundamental concerns for society. This study is a Global Climate Observing System (GCOS) concerted international effort to update the Earth heat inventory and presents an updated assessment of ocean warming estimates as well as new and updated estimates of heat gain in the atmosphere, cryosphere and land over the period 1960–2018. The study obtains a consistent long-term Earth system heat gain over the period 1971–2018, with a total heat gain of 358±37 ZJ, which is equivalent to a global heating rate of 0.47±0.1 W m−2. Over the period 1971–2018 (2010–2018), the majority of heat gain is reported for the global ocean with 89 % (90 %), with 52 % for both periods in the upper 700 m depth, 28 % (30 %) for the 700–2000 m depth layer and 9 % (8 %) below 2000 m depth. Heat gain over land amounts to 6 % (5 %) over these periods, 4 % (3 %) is available for the melting of grounded and floating ice, and 1 % (2 %) is available for atmospheric warming. Our results also show that EEI is not only continuing, but also increasing: the EEI amounts to 0.87±0.12 W m−2 during 2010–2018. Stabilization of climate, the goal of the universally agreed United Nations Framework Convention on Climate Change (UNFCCC) in 1992 and the Paris Agreement in 2015, requires that EEI be reduced to approximately zero to achieve Earth's system quasi-equilibrium. The amount of CO2 in the atmosphere would need to be reduced from 410 to 353 ppm to increase heat radiation to space by 0.87 W m−2, bringing Earth back towards energy balance. This simple number, EEI, is the most fundamental metric that the scientific community and public must be aware of as the measure of how well the world is doing in the task of bringing climate change under control, and we call for an implementation of the EEI into the global stocktake based on best available science. Continued quantification and reduced uncertainties in the Earth heat inventory can be best achieved through the maintenance of the current global climate observing system, its extension into areas of gaps in the sampling, and the establishment of an international framework for concerted multidisciplinary research of the Earth heat inventory as presented in this study. This Earth heat inventory is published at the German Climate Computing Centre (DKRZ, https://www.dkrz.de/, last access: 7 August 2020) under the DOI https://doi.org/10.26050/WDCC/GCOS_EHI_EXP_v2 (von Schuckmann et al., 2020)

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

A Large-Scale Epidemiological Study to Identify Bacteria Pathogenic to Pacific Oyster Crassostrea gigas and Correlation Between Virulence and Metalloprotease-like Activity

International audienc

REPAMO: a surveillance tool for mollusc health

At the present time losses due to diseases are one of main factors limiting the aquaculture development. Unceasing increase of exchanges between different countries favours the risk of introduction and propagation of new pathogen agents. At the beginning of the 90’s the European Union laid the surveillance of mollusc health inside each Member State in order to protect the safety of exchanges. Indeed few measures are available to protect molluscs from diseases. Only the prophylactic approach is possible; this approach is based on a zoosanitary surveillance of mollusc populations and/or a development of resistant populations against some diseases. Created in 1986, the French network for surveillance and monitoring of mollusc health (REPAMO) ensures the survey of shellfish health status along French coasts according to the Directives 91/67/EEC and 95/70/EC. The missions of the network are: (1) the surveillance of notifiable diseases present in France (Bonamiosis due to Bonamia ostreae and Marteiliosis due to Marteilia refringens), (2) the surveillance of health state of cultured and natural populations of molluscs, (3) the study of abnormal mortalities and (4) the control of exchanges from European country or from Third country. Therefore, the aims of REPAMO network are to prevent the introduction and spread of exotic diseases inside the different areas of French production and to study the impact of pathogens already present and to survey their evolution.