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A solution scan of societal options to reduce transmission and spread of respiratory viruses: SARS-CoV-2 as a case study.
Societal biosecurity - measures built into everyday society to minimize risks from pests and diseases - is an important aspect of managing epidemics and pandemics. We aimed to identify societal options for reducing the transmission and spread of respiratory viruses. We used SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) as a case study to meet the immediate need to manage the COVID-19 pandemic and eventually transition to more normal societal conditions, and to catalog options for managing similar pandemics in the future. We used a 'solution scanning' approach. We read the literature; consulted psychology, public health, medical, and solution scanning experts; crowd-sourced options using social media; and collated comments on a preprint. Here, we present a list of 519 possible measures to reduce SARS-CoV-2 transmission and spread. We provide a long list of options for policymakers and businesses to consider when designing biosecurity plans to combat SARS-CoV-2 and similar pathogens in the future. We also developed an online application to help with this process. We encourage testing of actions, documentation of outcomes, revisions to the current list, and the addition of further options
DarkCideS 1.0, a global database for bats in karsts and caves
Tanalgo, Krizler C., Tabora, John Aries G., de Oliveira, Hernani Fernandes Magalhães, Haelewaters, Danny, Beranek, Chad T., Otálora-Ardila, AÃda, Bernard, Enrico, Gonçalves, Fernando, Eriksson, Alan, Donnelly, Melissa, González, Joel Monzón, Ramos, Humberto Fernández, Rivas, Alberto Clark, Webala, Paul W., Deleva, Stanimira, Dalhoumi, Ridha, Maula, Jaycelle, Lizarro, Dennis, Aguirre, Luis F., Bouillard, Nils, Quibod, Ma. Niña Regina M., Barros, Jennifer, Turcios-Casco, Manfredo Alejandro, MartÃnez, Marcio, Ordoñez-Mazier, Diego Iván, Orellana, José Alejandro Soler, Ordoñez-Trejo, Eduardo J., Ordoñez, Danny, Chornelia, Ada, Lu, Jian Mei, Xing, Chen, Baniya, Sanjeev, Muylaert, Renata L., Dias-Silva, Leonardo Henrique, Ruadreo, Nittaya, Hughes, Alice Catherine (2022): DarkCideS 1.0, a global database for bats in karsts and caves. Scientific Data 9 (1): 155, DOI: 10.1038/s41597-022-01234-4, URL: http://dx.doi.org/10.1038/s41597-022-01234-
Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial
Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus
International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.
Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist
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