Study Design of a Cluster-Randomized Controlled Trial to Evaluate a Large-scale Distribution of Cook Stoves and Water Filters in Western Province, Rwanda

Background: In Rwanda, pneumonia and diarrhea are the first and second leading causes of death, respectively, among children under five. Household air pollution (HAP) resultant from cooking indoors with biomass fuels on traditional stoves is a significant risk factor for pneumonia, while consumption of contaminated drinking water is a primary cause of diarrheal disease. To date, there have been no largescale effectiveness trials of programmatic efforts to provide either improved cookstoves or household water filters at scale in a low-income country. In this paper we describe the design of a clusterrandomized trial to evaluate the impact of a national-level program to distribute and promote the use of improved cookstoves and advanced water filters to the poorest quarter of households in Rwanda. Methods/Design: We randomly allocated 72 sectors (administratively defined units) in Western Province to the intervention, with the remaining 24 sectors in the province serving as controls. In the intervention sectors, roughly 100,000 households received improved cookstoves and household water filters through a government-sponsored program targeting the poorest quarter of households nationally. The primary outcome measures are the incidence of acute respiratory infection (ARI) and diarrhea among children under five years of age. Over a one-year surveillance period, all cases of acute respiratory infection (ARI) and diarrhea identified by health workers in the study area will be extracted from records maintained at health facilities and by community health workers (CHW). In addition, we are conducting intensive, longitudinal data collection among a random sample of households in the study area for in-depth assessment of coverage, use, environmental exposures, and additional health measures. Discussion: Although previous research has examined the impact of providing household water treatment and improved cookstoves on child health, there have been no studies of national-level programs to deliver these interventions at scale in a developing country. The results of this study, the first RCT of a large-scale programmatic cookstove or household water filter intervention, will inform global efforts to reduce childhood morbidity and mortality from diarrheal disease and pneumonia

Inflammasome activation in neutrophils of patients with severe COVID-19

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Aymonnier, K., Ng, J., Fredenburgh, L. E., Zambrano-Vera, K., Muenzer, P., Gutch, S., Fukui, S., Desjardins, M., Subramaniam, M., Baron, R. M., Raby, B. A., Perrella, M. A., Lederer, J. A., & Wagner, D. D. Inflammasome activation in neutrophils of patients with severe COVID-19. Blood Advances, 6(7), (2022): 2001–2013, https://doi.org/10.1182/bloodadvances.2021005949.Infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engages the inflammasome in monocytes and macrophages and leads to the cytokine storm in COVID-19. Neutrophils, the most abundant leukocytes, release neutrophil extracellular traps (NETs), which have been implicated in the pathogenesis of COVID-19. Our recent study shows that activation of the NLRP3 inflammasome is important for NET release in sterile inflammation. However, the role of neutrophil inflammasome formation in human disease is unknown. We hypothesized that SARS-CoV-2 infection may induce inflammasome activation in neutrophils. We also aimed to assess the localization of inflammasome formation (ie, apoptosis-associated speck-like protein containing a CARD [ASC] speck assembly) and timing relative to NETosis in stimulated neutrophils by real-time video microscopy. Neutrophils isolated from severe COVID-19 patients demonstrated that ∼2% of neutrophils in both the peripheral blood and tracheal aspirates presented ASC speck. ASC speck was observed in neutrophils with an intact poly-lobulated nucleus, suggesting early formation during neutrophil activation. Additionally, 40% of nuclei were positive for citrullinated histone H3, and there was a significant correlation between speck formation and nuclear histone citrullination. Time-lapse microscopy in lipopolysaccharide -stimulated neutrophils from fluorescent ASC reporter mice showed that ASC speck formed transiently and at the microtubule organizing center long before NET release. Our study shows that ASC speck is present in neutrophils from COVID-19 patients with respiratory failure and that it forms early in NETosis. Our findings suggest that inhibition of neutrophil inflammasomes may be beneficial in COVID-19.P.M. received an Individual Marie Skłodowska-Curie Actions fellowship by the European Commission (796365 - COAGULANT). This work was supported by the National Institutes of Health (NIH)/Research Program Award grant R35 HL135765 (D.W.), by the NIH/National Heart, Lung, and Blood Institute grant T32 HL007633-35 (J.N.), and by the NIH/National Institute of Allergy and Infectious Diseases grant U01AI138318 (J.L and M.P); by the Massachusetts Consortium on Pathogen Readiness (MassCPR) Evergrande COVID‐19 Response Fund Award to B.R.; and by a generous gift to D.W. from the Steven Berzin family

Study design of a cluster-randomized controlled trial to evaluate a large-scale distribution of cook stoves and water filters in Western Province, Rwanda.

BACKGROUND: In Rwanda, pneumonia and diarrhea are the first and second leading causes of death, respectively, among children under five. Household air pollution (HAP) resultant from cooking indoors with biomass fuels on traditional stoves is a significant risk factor for pneumonia, while consumption of contaminated drinking water is a primary cause of diarrheal disease. To date, there have been no large-scale effectiveness trials of programmatic efforts to provide either improved cookstoves or household water filters at scale in a low-income country. In this paper we describe the design of a cluster-randomized trial to evaluate the impact of a national-level program to distribute and promote the use of improved cookstoves and advanced water filters to the poorest quarter of households in Rwanda. METHODS/DESIGN: We randomly allocated 72 sectors (administratively defined units) in Western Province to the intervention, with the remaining 24 sectors in the province serving as controls. In the intervention sectors, roughly 100,000 households received improved cookstoves and household water filters through a government-sponsored program targeting the poorest quarter of households nationally. The primary outcome measures are the incidence of acute respiratory infection (ARI) and diarrhea among children under five years of age. Over a one-year surveillance period, all cases of acute respiratory infection (ARI) and diarrhea identified by health workers in the study area will be extracted from records maintained at health facilities and by community health workers (CHW). In addition, we are conducting intensive, longitudinal data collection among a random sample of households in the study area for in-depth assessment of coverage, use, environmental exposures, and additional health measures. DISCUSSION: Although previous research has examined the impact of providing household water treatment and improved cookstoves on child health, there have been no studies of national-level programs to deliver these interventions at scale in a developing country. The results of this study, the first RCT of a large-scale programmatic cookstove or household water filter intervention, will inform global efforts to reduce childhood morbidity and mortality from diarrheal disease and pneumonia. TRIAL REGISTRATION: This trial is registered at Clinicaltrials.gov (NCT02239250)

Effects of a large-scale distribution of water filters and natural draft rocket-style cookstoves on diarrhea and acute respiratory infection: A cluster-randomized controlled trial in Western Province, Rwanda.

BACKGROUND: Unsafe drinking water and household air pollution (HAP) are major causes of morbidity and mortality among children under 5 in low and middle-income countries. Household water filters and higher-efficiency biomass-burning cookstoves have been widely promoted to improve water quality and reduce fuel use, but there is limited evidence of their health effects when delivered programmatically at scale. METHODS AND FINDINGS: In a large-scale program in Western Province, Rwanda, water filters and portable biomass-burning natural draft rocket-style cookstoves were distributed between September and December 2014 and promoted to over 101,000 households in the poorest economic quartile in 72 (of 96) randomly selected sectors in Western Province. To assess the effects of the intervention, between August and December, 2014, we enrolled 1,582 households that included a child under 4 years from 174 randomly selected village-sized clusters, half from intervention sectors and half from nonintervention sectors. At baseline, 76% of households relied primarily on an improved source for drinking water (piped, borehole, protected spring/well, or rainwater) and over 99% cooked primarily on traditional biomass-burning stoves. We conducted follow-up at 3 time-points between February 2015 and March 2016 to assess reported diarrhea and acute respiratory infections (ARIs) among children <5 years in the preceding 7 days (primary outcomes) and patterns of intervention use, drinking water quality, and air quality. The intervention reduced the prevalence of reported child diarrhea by 29% (prevalence ratio [PR] 0.71, 95% confidence interval [CI] 0.59-0.87, p = 0.001) and reported child ARI by 25% (PR 0.75, 95% CI 0.60-0.93, p = 0.009). Overall, more than 62% of households were observed to have water in their filters at follow-up, while 65% reported using the intervention stove every day, and 55% reported using it primarily outdoors. Use of both the intervention filter and intervention stove decreased throughout follow-up, while reported traditional stove use increased. The intervention reduced the prevalence of households with detectable fecal contamination in drinking water samples by 38% (PR 0.62, 95% CI 0.57-0.68, p < 0.0001) but had no significant impact on 48-hour personal exposure to log-transformed fine particulate matter (PM2.5) concentrations among cooks (β = -0.089, p = 0.486) or children (β = -0.228, p = 0.127). The main limitations of this trial include the unblinded nature of the intervention, limited PM2.5 exposure measurement, and a reliance on reported intervention use and reported health outcomes. CONCLUSIONS: Our findings indicate that the intervention improved household drinking water quality and reduced caregiver-reported diarrhea among children <5 years. It also reduced caregiver-reported ARI despite no evidence of improved air quality. Further research is necessary to ascertain longer-term intervention use and benefits and to explore the potential synergistic effects between diarrhea and ARI. TRIAL REGISTRATION: Clinical Trials.gov NCT02239250

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde

Measurement of the top quark pair cross section with ATLAS in pp collisions at √s=7 TeV using final states with an electron or a muon and a hadronically decaying τ lepton

A measurement of the cross section of top quark pair production in proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 7 TeV is reported. The data sample used corresponds to an integrated luminosity of 2.05 fb -1. Events with an isolated electron or muon and a τ lepton decaying hadronically are used. In addition, a large missing transverse momentum and two or more energetic jets are required. At least one of the jets must be identified as originating from a b quark. The measured cross section, σtt-=186±13(stat.)±20(syst.)±7(lumi.) pb, is in good agreement with the Standard Model prediction

Hunt for new phenomena using large jet multiplicities and missing transverse momentum with ATLAS in 4.7 fb−1 of √s=7 TeV proton-proton collisions

Results are presented of a search for new particles decaying to large numbers of jets in association with missing transverse momentum, using 4.7 fb−1 of pp collision data at s√=7TeV collected by the ATLAS experiment at the Large Hadron Collider in 2011. The event selection requires missing transverse momentum, no isolated electrons or muons, and from ≥6 to ≥9 jets. No evidence is found for physics beyond the Standard Model. The results are interpreted in the context of a MSUGRA/CMSSM supersymmetric model, where, for large universal scalar mass m 0, gluino masses smaller than 840 GeV are excluded at the 95% confidence level, extending previously published limits. Within a simplified model containing only a gluino octet and a neutralino, gluino masses smaller than 870 GeV are similarly excluded for neutralino masses below 100 GeV