Lives saved with vaccination for 10 pathogens across 112 countries in a pre-COVID-19 world.

BackgroundVaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae, and yellow fever over the years 2000-2030 across 112 countries.MethodsTwenty-one mathematical models estimated disease burden using standardised demographic and immunisation data. Impact was attributed to the year of vaccination through vaccine-activity-stratified impact ratios.ResultsWe estimate 97 (95%CrI[80, 120]) million deaths would be averted due to vaccination activities over 2000-2030, with 50 (95%CrI[41, 62]) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI[41, 69]) million more deaths would occur over their lifetimes without vaccination against these diseases.ConclusionsThis study represents the largest assessment of vaccine impact before COVID-19-related disruptions and provides motivation for sustaining and improving global vaccination coverage in the future.FundingVIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill and Melinda Gates Foundation (BMGF) (BMGF grant number: OPP1157270 / INV-009125). Funding from Gavi is channelled via VIMC to the Consortium's modelling groups (VIMC-funded institutions represented in this paper: Imperial College London, London School of Hygiene and Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Métiers, Emory University, National University of Singapore). Funding from BMGF was used for salaries of the Consortium secretariat (authors represented here: TBH, MJ, XL, SE-L, JT, KW, NMF, KAMG); and channelled via VIMC for travel and subsistence costs of all Consortium members (all authors). We also acknowledge funding from the UK Medical Research Council and Department for International Development, which supported aspects of VIMC's work (MRC grant number: MR/R015600/1).JHH acknowledges funding from National Science Foundation Graduate Research Fellowship; Richard and Peggy Notebaert Premier Fellowship from the University of Notre Dame. BAL acknowledges funding from NIH/NIGMS (grant number R01 GM124280) and NIH/NIAID (grant number R01 AI112970). The Lives Saved Tool (LiST) receives funding support from the Bill and Melinda Gates Foundation.This paper was compiled by all coauthors, including two coauthors from Gavi. Other funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication

Living precariously: property guardianship and the flexible city

In this paper we examine the precarious everyday geographies of property guardianship in the United Kingdom. Temporary property guardianship is a relatively new form of insecure urban dwelling existing in the grey area between informal occupation, the security industry and housing. Young individuals, usually in precarious employment, apply to intermediary companies to become temporary 'guardians' in metropolitan centres, most notably in London. The scheme allows guardians to pay below market rent to live in unusual locations while ‘performing’ live-in security arrangements that are not considered as a form of ‘work’. The experiences of becoming and living as a property guardian can be ambivalent and contradictory: guardians express economic and social advantages to being temporary, while also exposing underlying anxieties with ‘flexible living’. In this paper we offer a detailed description of the various practices of property guardianship and how they must be understood on the one hand, in light of recent geographical scholarship on housing insecurity and, on the other hand, as an example of a precarious subjectivity that has become normalised in recent decades in cities of the global North. Drawing on indepth interviews with long-term property guardians in London, we unpack the narratives and rationales of university educated and highly skilled individuals for whom the city is a site of intensified insecurity and flexible negotiations. In the end, we conclude that the form of permanent temporariness experienced by property guardians needs to be understood as a symptom of wider dynamics of work and life precarisation in urban centers and argue that it is imperative to extend recent geographical debates around work and life insecurity to include new housing practices and their role in co-constituting urban precarity

Microbial community structure mediates response of soil C decomposition to litter addition and warming

Microbial activity has been highlighted as one of the main unknowns controlling the fate and turnover of soil organic matter (SOM) in response to climate change. How microbial community structure and function may (or may not) interact with increasing temperature to impact the fate and turnover of SOM, in particular when combined with changes in litter chemistry, is not well understood. The primary aim of this study was to determine if litter chemistry impacted the decomposition of soil and litter-derived carbon (C), and its interaction with temperature, and whether this response was controlled by microbial community structure and function. Fresh or pre-incubated eucalyptus leaf litter (13C enriched) was added to a woodland soil and incubated at 12, 22, or 32 �C. We tracked the movement of litter and soilderived C into CO2, water-extractable organic carbon (WEOC), and microbial phospholipids (PLFA). The litter additions produced significant changes in every parameter measured, while temperature, interacting with litter chemistry, predominately affected soil C respiration (priming and temperature sensitivity), microbial community structure, and the metabolic quotient (a proxy for microbial carbon use efficiency [CUE]). The direction of priming varied with the litter additions (negative with fresh litter, positive with pre-incubated litter) and was related to differences in the composition of microbial communities degrading soil-C, particularly gram-positive and gram-negative bacteria, resulting from litter addition. Soil-C decomposition in both litter treatments was more temperature sensitive (higher Q10) than in the soil-only control, and soil-C priming became increasingly positive with temperature. However, microbes utilizing soil-C in the litter treatments had higher CUE, suggesting the longer-term stability of soil-C may be increased at higher temperature with litter addition. Our results show that in the same soil, the growth of distinct microbial communities can alter the turnover and fate of SOM and, in the context of global change, its response to temperature

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

One Year of Surface-Based Temperature Inversions at Dome C, Antarctica

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Improved measurements of the neutrino mixing angle Ɵ<inf>13</inf> with the double chooz detector

The Double Chooz experiment presents improved measurements of the neutrino mixing angle Ɵ13 using the data collected in 467.90 live days from a detector positioned at an average distance of 1050m from two reactor cores at the Chooz nuclear power plant. Several novel techniques have been developed to achieve significant reductions of the backgrounds and systematic uncertainties with respect to previous publications, whereas the efficiency of the (Formula Presented.) signal has increased. The value of Ɵ13 is measured to be sin22Ɵ13 = 0.090-0.029+0.032 from a fit to the observed energy spectrum. Deviations from the reactor (Formula Presented.) prediction observed above a prompt signal energy of 4MeV and possible explanations are also reported. A consistent value of Ɵ13 is obtained from a fit to the observed rate as a function of the reactor power independently of the spectrum shape and background estimation, demonstrating the robustness of the Ɵ13 measurement despite the observed distortion