Experimental evidence that livestock grazing intensity affects the activity of a generalist predator

Open Access funded by Natural Environment Research CouncilPeer reviewedPublisher PD

Multi-species population indices for sets of species including rare, disappearing or newly occurring species

NI is funded by Natural Environment Research Council award NE/R016429/1 as part of the UK-SCAPE programme delivering National Capability.Multi-species indices (MSI) are widely used as ecological indicators and as instruments to inform environmental policies. Many of these indices combine species-specific estimates of relative population sizes using the geometric mean. Because the geometric mean is not defined when values of zero occur, usually only commoner species are included in MSIs and zero values are replaced by a small non-zero value. The latter can exhibit an arbitrary influence on the geometric mean MSI. Here, we show how the compound Poisson and the negative binomial model can be used in such cases to obtain an MSI that has similar features to the geometric mean, including weighting halving and doubling of a species’ population equally. In contrast to the geometric mean, these two statistical models can handle zero values in population sizes and thus accommodate newly occurring and temporarily or permanently disappearing species in the MSI. We compare the MSIs obtained by the two statistical models with the geometric mean MSI and measure sensitivity to changes in evenness and to population trends in rare and abundant species. Additionally, we outline sources of uncertainty and discuss how to measure them. We found that, in contrast to the geometric mean and the negative binomial MSI, the compound Poisson MSI is less sensitive to changes in evenness when total abundance is constant. Further, we found that the compound Poisson model can be influenced more than the other two methods by trends of species showing a low interannual variance. The negative binomial MSI is less sensitive to trends in rare species compared with the other two methods, and similarly sensitive to trends in abundant species as the geometric mean. While the two new MSIs have the advantage that they are not arbitrarily influenced by rare, newly appearing and disappearing species, both do not weight all species equally. We recommend replacing the geometric mean MSI with either compound Poisson or negative binomial when there are species with a population size of zero in some years having a strong influence on the geometric mean MSI. Further, we recommend providing additional information alongside the MSIs. For example, it is particularly important to give an evenness index in addition to the compound Poisson MSI and to indicate the number of disappearing and newly occurring species alongside the negative binomial MSI.Publisher PDFPeer reviewe

Finding the principles of the commons: a report of the Force11 Scholarly Communications Working Group

Open access[No abstract available]Ye

Main nutrient patterns and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study.

BACKGROUND: Much of the current literature on diet-colorectal cancer (CRC) associations focused on studies of single foods/nutrients, whereas less is known about nutrient patterns. We investigated the association between major nutrient patterns and CRC risk in participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: Among 477 312 participants, intakes of 23 nutrients were estimated from validated dietary questionnaires. Using results from a previous principal component (PC) analysis, four major nutrient patterns were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed for the association of each of the four patterns and CRC incidence using multivariate Cox proportional hazards models with adjustment for established CRC risk factors. RESULTS: During an average of 11 years of follow-up, 4517 incident cases of CRC were documented. A nutrient pattern characterised by high intakes of vitamins and minerals was inversely associated with CRC (HR per 1 s.d.=0.94, 95% CI: 0.92-0.98) as was a pattern characterised by total protein, riboflavin, phosphorus and calcium (HR (1 s.d.)=0.96, 95% CI: 0.93-0.99). The remaining two patterns were not significantly associated with CRC risk. CONCLUSIONS: Analysing nutrient patterns may improve our understanding of how groups of nutrients relate to CRC

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Études immunothérapeutiques et caractérisation de la structure et de la fonction de la glycoprotéine d'attachement d'un paramyxovirus émergent (le virus NIPAH)

Depuis 1999, le virus Nipah un paramyxovirinae est l'agent étiologique d'épidémies humaines d'encéphalite mortelle en Asie. La vaste répartition géographique de son réservoir naturel, la chauve-souris Ptéropus, laisse présager de nouvelles épidémies. Nous avons identifié deux antigènes du virus Nipah, les glycoprotéines G et F, inducteurs d'une réponse immunitaire protectrice, puis montré qu'un traitement curatif, à l'aide d'anticorps monoclonaux neutralisants spécifiques de G ou de F, induit une protection stérilisante contre l'infection mortelle par ce virus. Nous avons, par ailleurs, identifié plusieurs acides aminés de G, localisés à la surface de la tête globulaire de la protéine virale, susceptibles de participer à son interaction avec les(s) récepteur(s) cellulaire(s). Ces études initient le développement d'un traitement curatif et préventif contre l'infection par le virus Nipah et l'étude moléculaire de l'interaction du virus avec son ou ses récepteur(s) cellulaire(s)LYON1-BU.Sciences (692662101) / SudocSudocFranceF

Étude moléculaire de la glycoprotéine d'attachement du virus de la rougeole (identification et caractérisation des domaines d'interaction avec les récepteurs CD46 et SLAM)

Le virus de la rougeole (VR) est encore responsable d'une forte mortalité infantile, due à l'immunosuppression transitoire sévère qu'il engendre. Ce virus enveloppé possède deux glycoprotéines transmembranaires dont l'hémagglutinine H. Nos travaux ont porté sur l'identification de domaines de la protéine VRH responsables de l'interaction avec les deux récepteurs cellulaires identifiés : la protéine SLAM, utilisée par toutes les souches du VR, et la protéine CD46, qui ne serait utilisée que par les souches vaccinales du VR. Il subsiste toutefois une controverse quant à la possibilité d'une interaction entre CD46 et les souches sauvages circulantes du VR. Nos travaux contribuent à l'analyse du tropisme du VR et permettent (i) la production de vecteurs thérapeutiques, ou (ii) de virus recombinants interagissant avec un seul récepteur, outils indispensables à la compréhension des mécanismes sous-jacents la pathologie et l'immunosuppression induites par l'infection rougeoleuse naturelleLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Étude moléculaire des glycoprotéines d'attachement des Henipavirus (identification et caractérisation des domaines responsables de l'interaction avec les récepteurs cellulaires, éphrineB2 et éphrineB3)

Les Henipavirus, le virus Nipah (VN) et le virus Hendra (VH), sont des virus zoonotiques émergents, responsables de pathologies chez l homme et les animaux. Leur virulence élevée et l absence de traitements disponibles ont conduit à leur classification en pathogène de niveau 4. L entrée de ces virus dans la cellule hôte est sous contrôle de deux glycoprotéines virales, la protéine d attachement (G) et la protéine de fusion (F). Nous avons identifié plusieurs résidus de la protéine G du VN, importants pour la liaison au récepteur cellulaire, l éphrine B2. Ces résidus forment un site contigu, localisé à la surface sur le haut de la tête globulaire de la protéine d attachement du VN. Nous avons également montré que le site de liaison à l éphrine B2 sur la protéine G du VH se trouvait dans une localisation similaire et impliquait en grande majorité les mêmes résidus. Nous avons également étudié le rôle potentiel de ces résidus dans la liaison à l éphrine B3, un récepteur alternatif du VN. Nos résultats indiquent que le VH pourrait utiliser l éphrine B3 comme récepteurThe Henipaviruses - Nipah (NiV) and Hendra (HeV) - are recently emergent zoonotic paramyxoviruses, responsible for pathologies in the man and the animals. Their high virulence and the absence of available treatments led to their classification into P4 pathogens. The entry of these viruses in the host cell is under control of two glycoproteins, the attachment glycoprotein (G) and the fusion protein (F). We identified several residues of the attachment glycoprotein of the NiV (NiV-G), potentially participating in receptor-binding, the ephrinB2. Ours results suggest that a receptor-binding site localizes on the top surface of the NiV-G globular head. We also showed that the site responsible for ephrinB2 interaction on the globular head of the HeV attachment glycoprotein (HeV-G) is in an identical location to that predicted for NiV-G. We also tested the attachment glycoprotein residues of the HeV and NiV for ephrinB3 interaction, an alternate receptor of the NiV. Our results indicate that the HeV could use ephrinB3 as receptor.LYON1-BU.Sciences (692662101) / SudocSudocFranceF