33 research outputs found
Digital measurement of SARS-CoV-2 transmission risk from 7 million contacts
How likely is it to become infected by SARS-CoV-2 after being exposed? Almost everyone wondered about this question during the COVID-19 pandemic. Contact-tracing apps1,2 recorded measurements of proximity3 and duration between nearby smartphones. Contactsâindividuals exposed to confirmed casesâwere notified according to public health policies such as the 2âm, 15âmin guideline4,5, despite limited evidence supporting this threshold. Here we analysed 7âmillion contacts notified by the National Health Service COVID-19 app6,7 in England and Wales to infer how app measurements translated to actual transmissions. Empirical metrics and statistical modelling showed a strong relation between app-computed risk scores and actual transmission probability. Longer exposures at greater distances had risk similar to that of shorter exposures at closer distances. The probability of transmission confirmed by a reported positive test increased initially linearly with duration of exposure (1.1% per hour) and continued increasing over several days. Whereas most exposures were short (median 0.7âh, interquartile range 0.4â1.6), transmissions typically resulted from exposures lasting between 1âh and several days (median 6âh, interquartile range 1.4â28). Households accounted for about 6% of contacts but 40% of transmissions. With sufficient preparation, privacy-preserving yet precise analyses of risk that would inform public health measures, based on digital contact tracing, could be performed within weeks of the emergence of a new pathogen
Crowdsourced mapping of unexplored target space of kinase inhibitors
Despite decades of intensive search for compounds that modulate the activity of particular protein targets, a large proportion of the human kinome remains as yet undrugged. Effective approaches are therefore required to map the massive space of unexplored compound-kinase interactions for novel and potent activities. Here, we carry out a crowdsourced benchmarking of predictive algorithms for kinase inhibitor potencies across multiple kinase families tested on unpublished bioactivity data. We find the top-performing predictions are based on various models, including kernel learning, gradient boosting and deep learning, and their ensemble leads to a predictive accuracy exceeding that of single-dose kinase activity assays. We design experiments based on the model predictions and identify unexpected activities even for under-studied kinases, thereby accelerating experimental mapping efforts. The open-source prediction algorithms together with the bioactivities between 95 compounds and 295 kinases provide a resource for benchmarking prediction algorithms and for extending the druggable kinome. The IDG-DREAM Challenge carried out crowdsourced benchmarking of predictive algorithms for kinase inhibitor activities on unpublished data. This study provides a resource to compare emerging algorithms and prioritize new kinase activities to accelerate drug discovery and repurposing efforts
REQUITE: A prospective multicentre cohort study of patients undergoing radiotherapy for breast, lung or prostate cancer
Purpose: REQUITE aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy. The purpose of this article is to provide summary descriptive data.
Methods: An international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017. Target recruitment was 5300 patients. Eligible patients had breast, prostate or lung cancer and planned potentially curable radiotherapy. Radiotherapy was prescribed according to local regimens, but centres used standardised data collection forms. Pre-treatment blood samples were collected. Patients were followed for a minimum of 12 (lung) or 24 (breast/prostate) months and summary descriptive statistics were generated.
Results: The study recruited 2069 breast (99% of target), 1808 prostate (86%) and 561 lung (51%) cancer patients. The centralised, accessible database includes: physician-(47,025 forms) and patient-(54,901) reported outcomes; 11,563 breast photos; 17,107 DICOMs and 12,684 DVHs. Imputed genotype data are available for 4223 patients with European ancestry (1948 breast, 1728 prostate, 547 lung). Radiation-induced lymphocyte apoptosis (RILA) assay data are available for 1319 patients. DNA (n = 4409) and PAXgene tubes (n = 3039) are stored in the centralised biobank. Example prevalences of 2-year (1-year for lung) grade >= 2 CTCAE toxicities are 13% atrophy (breast), 3% rectal bleeding (prostate) and 27% dyspnoea (lung).
Conclusion: The comprehensive centralised database and linked biobank is a valuable resource for the radiotherapy community for validating predictive models and biomarkers.
Patient summary: Up to half of cancer patients undergo radiation therapy and irradiation of surrounding healthy tissue is unavoidable. Damage to healthy tissue can affect short-and long-term quality-of-life. Not all patients are equally sensitive to radiation "damage" but it is not possible at the moment to identify those who are. REQUITE was established with the aim of trying to understand more about how we could predict radiation sensitivity. The purpose of this paper is to provide an overview and summary of the data and material available.
In the REQUITE study 4400 breast, prostate and lung cancer patients filled out questionnaires and donated blood. A large amount of data was collected in the same way. With all these data and samples a database and biobank were created that showed it is possible to collect this kind of information in a standardised way across countries.
In the future, our database and linked biobank will be a resource for research and validation of clinical predictors and models of radiation sensitivity. REQUITE will also enable a better understanding of how many people suffer with radiotherapy toxicity
Ătudes cinĂ©tiques dans le domaine des dĂ©rivĂ©s polycycliques aromatiques. II. Hydrolyse basique d'esters carboxyliques
Les paramĂštres d'Arrhenius de l'hydrolyse par la soude caustique, dans l'Ă©thanol Ă 85%, des esters suivants: benzoate d'Ă©thyle, naphtoatesâ1 et â2 d'Ă©thyle, phĂ©nanthroatesâ9, â2 et â3 d'Ă©thyle et anthroateâ9 d'Ă©thyle ont Ă©tĂ© dĂ©terminĂ©s. Copyright © 1955 Verlag GmbH & Co. KGaA, WeinheimSCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe
Etudes cinĂ©tiques dans le domaine des dĂ©rivĂ©s polycycliques aromatiques VI. Hydrolyse basique du benzophĂ©nanthrĂšneâ3,4âcarboxylateâ1 d'Ă©thyle
ARRHENIUS parameters of the alkaline hydrolysis of ethyl 3,4âbenzophenanthreneâ1âcarboxylate in water (15%) â ethanol (85%) have been determined: E = 16,39 kcal, log PZ = 8,66, k2,(25°C) =4,40.10â4.These results indicate that the rate constant of this reaction is not affected by the non planar nature of the 3,4âbenzophenanthrene system. Copyright © 1959 Verlag GmbH & Co. KGaA, WeinheimSCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe
Ătudes cinĂ©tiques dans le domaine des dĂ©rivĂ©s polycycliques aromatiques. IV. RĂ©actions d'Ă©change S N
Exploring for antimicrobial compounds in complex natural mixtures using similarity analysis
status: publishe
A novel top-down approach to assess the antimicrobial activity of 121 essential oils against 8 diverse pathogenic bacteria and fungi
status: publishe