Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Cognitive radio for high speed railway through dynamic and opportunistic spectrum reuse

TRA2014 Transport Research Arena 2014 - Transport Solutions: from Research to Deployment - Innovate Mobility, Mobilise Innovation! 14-17 Apr 2014 Paris La Défense (France)International audienceThe integration of all the heterogeneous wireless networks deployed along European railway lines constitutes a key technical challenge to improve global efficiency of railway system. Emerging Cognitive Radio (CR) technologies can answer this challenge. The paper presents the first results obtained in the ANR project CORRIDOR (Cognitive Radio for High Speed Railway through Dynamic and Opportunistic spectrum Reuse) which is the first research project devoted to CR systems for Railway in France, taking into account very demanding railway applications: GSM-R which is the radio link of the ERTMS system, and other operational needs such as video surveillance of the inside of trains, data related to maintenance and Internet on board for passengers

Cognitive radio for high speed railway through dynamic and opportunistic spectrum reuse

International audienceThe integration of all the heterogeneous wireless networks deployed along European railway lines constitutes a key technical challenge to improve global efficiency of railway system. Emerging Cognitive Radio (CR) technologies can answer this challenge. The paper presents the first results obtained in the ANR project CORRIDOR (Cognitive Radio for High Speed Railway through Dynamic and Opportunistic spectrum Reuse) which is the first research project devoted to CR systems for Railway in France, taking into account very demanding railway applications: GSM-R which is the radio link of the ERTMS system, and other operational needs such as video surveillance of the inside of trains, data related to maintenance and Internet on board for passengers

Cognitive radio for high speed railway through dynamic and opportunistic spectrum reuse

International audienceThe integration of all the heterogeneous wireless networks deployed along European railway lines constitutes a key technical challenge to improve global efficiency of railway system. Emerging Cognitive Radio (CR) technologies can answer this challenge. The paper presents the first results obtained in the ANR project CORRIDOR (Cognitive Radio for High Speed Railway through Dynamic and Opportunistic spectrum Reuse) which is the first research project devoted to CR systems for Railway in France, taking into account very demanding railway applications: GSM-R which is the radio link of the ERTMS system, and other operational needs such as video surveillance of the inside of trains, data related to maintenance and Internet on board for passengers

Cognitive radio for high speed railway through dynamic and opportunistic spectrum reuse

TRA2014 Transport Research Arena 2014 - Transport Solutions: from Research to Deployment - Innovate Mobility, Mobilise Innovation! 14-17 Apr 2014 Paris La Défense (France)International audienceThe integration of all the heterogeneous wireless networks deployed along European railway lines constitutes a key technical challenge to improve global efficiency of railway system. Emerging Cognitive Radio (CR) technologies can answer this challenge. The paper presents the first results obtained in the ANR project CORRIDOR (Cognitive Radio for High Speed Railway through Dynamic and Opportunistic spectrum Reuse) which is the first research project devoted to CR systems for Railway in France, taking into account very demanding railway applications: GSM-R which is the radio link of the ERTMS system, and other operational needs such as video surveillance of the inside of trains, data related to maintenance and Internet on board for passengers

Cognitive radio for high speed railway through dynamic and opportunistic spectrum reuse

TRA2014 Transport Research Arena 2014 - Transport Solutions: from Research to Deployment - Innovate Mobility, Mobilise Innovation! 14-17 Apr 2014 Paris La Défense (France)International audienceThe integration of all the heterogeneous wireless networks deployed along European railway lines constitutes a key technical challenge to improve global efficiency of railway system. Emerging Cognitive Radio (CR) technologies can answer this challenge. The paper presents the first results obtained in the ANR project CORRIDOR (Cognitive Radio for High Speed Railway through Dynamic and Opportunistic spectrum Reuse) which is the first research project devoted to CR systems for Railway in France, taking into account very demanding railway applications: GSM-R which is the radio link of the ERTMS system, and other operational needs such as video surveillance of the inside of trains, data related to maintenance and Internet on board for passengers

Sex differences in oncogenic mutational processes

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Peer reviewe

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that -80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAFPeer reviewe