Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

PARP1 proximity proteomics reveals interaction partners at stressed replication forks

PARP1 mediates poly-ADP-ribosylation of proteins on chromatin in response to different types of DNA lesions. PARP inhibitors are used for the treatment of BRCA1/2-deficient breast, ovarian, and prostate cancer. Loss of DNA replication fork protection is proposed as one mechanism that contributes to the vulnerability of BRCA1/2-deficient cells to PARP inhibitors. However, the mechanisms that regulate PARP1 activity at stressed replication forks remain poorly understood. Here, we performed proximity proteomics of PARP1 and isolation of proteins on stressed replication forks to map putative PARP1 regulators. We identified TPX2 as a direct PARP1-binding protein that regulates the auto-ADP-ribosylation activity of PARP1. TPX2 interacts with DNA damage response proteins and promotes homology-directed repair of DNA double-strand breaks. Moreover, TPX2 mRNA levels are increased in BRCA1/2-mutated breast and prostate cancers, and high TPX2 expression levels correlate with the sensitivity of cancer cells to PARP-trapping inhibitors. We propose that TPX2 confers a mitosis-independent function in the cellular response to replication stress by interacting with PARP1

Design, Qualification, and On Orbit Performance of the CALIPSO Aerosol Lidar Transmitter

The laser transmitter for the CALIPSO aerosol lidar mission has been operating on orbit as planned since June 2006. This document discusses the optical and laser system design and qualification process that led to this success. Space-qualifiable laser design guidelines included the use of mature laser technologies, the use of alignment sensitive resonator designs, the development and practice of stringent contamination control procedures, the operation of all optical components at appropriately derated levels, and the proper budgeting for the space-qualification of the electronics and software

Nicotine Acts on Growth Plate Chondrocytes to Delay Skeletal Growth through the α7 Neuronal Nicotinic Acetylcholine Receptor

BACKGROUND: Cigarette smoking adversely affects endochondral ossification during the course of skeletal growth. Among a plethora of cigarette chemicals, nicotine is one of the primary candidate compounds responsible for the cause of smoking-induced delayed skeletal growth. However, the possible mechanism of delayed skeletal growth caused by nicotine remains unclarified. In the last decade, localization of neuronal nicotinic acetylcholine receptor (nAChR), a specific receptor of nicotine, has been widely detected in non-excitable cells. Therefore, we hypothesized that nicotine affect growth plate chondrocytes directly and specifically through nAChR to delay skeletal growth. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effect of nicotine on human growth plate chondrocytes, a major component of endochondral ossification. The chondrocytes were derived from extra human fingers. Nicotine inhibited matrix synthesis and hypertrophic differentiation in human growth plate chondrocytes in suspension culture in a concentration-dependent manner. Both human and murine growth plate chondrocytes expressed alpha7 nAChR, which constitutes functional homopentameric receptors. Methyllycaconitine (MLA), a specific antagonist of alpha7 nAChR, reversed the inhibition of matrix synthesis and functional calcium signal by nicotine in human growth plate chondrocytes in vitro. To study the effect of nicotine on growth plate in vivo, ovulation-controlled pregnant alpha7 nAChR +/- mice were given drinking water with or without nicotine during pregnancy, and skeletal growth of their fetuses was observed. Maternal nicotine exposure resulted in delayed skeletal growth of alpha7 nAChR +/+ fetuses but not in alpha7 nAChR -/- fetuses, implying that skeletal growth retardation by nicotine is specifically mediated via fetal alpha7 nAChR. CONCLUSIONS/SIGNIFICANCE: These results suggest that nicotine, from cigarette smoking, acts directly on growth plate chondrocytes to decrease matrix synthesis, suppress hypertrophic differentiation via alpha7 nAChR, leading to delayed skeletal growth

A Unified Representation of Gas-Phase Element Depletions in the Interstellar Medium

A study of gas-phase element abundances reported in the literature for 17 different elements sampled over 243 sight lines in the local part of our Galaxy reveals that the depletions into solid form (dust grains) are extremely well characterized by trends that employ only three kinds of parameters. One is an index that describes the overall level of depletion applicable to the gas in any particular sight line, and the other two represent linear coefficients that describe how to derive each element's depletion from this sight-line parameter. The information from this study reveals the relative proportions of different elements that are incorporated into dust at different stages of grain growth. An extremely simple scheme is proposed for deriving the dust contents and metallicities of absorption-line systems that are seen in the spectra of distant quasars or the optical afterglows of gamma-ray bursts. Contrary to presently accepted thinking, the elements sulfur and krypton appear to show measurable changes in their depletions as the general levels of depletions of other elements increase, although more data are needed to ascertain whether or not these findings truly compelling. Nitrogen appears to show no such increase. The incorporation of oxygen into solid form in the densest gas regions far exceeds the amounts that can take the form of silicates or metallic oxides; this conclusion is based on differential measurements of depletion and thus is unaffected by uncertainties in the solar abundance reference scale.Comment: 166 pages, 21 figures, pages 116-166 contain detailed tabulations that may not be of interest to most readers. Accepted for publication in the Astrophysical Journa

ZFOURGE/CANDELS: On The Evolution Of M* Galaxy Progenitors From Z=3 To 0.5

Galaxies with stellar masses near M* contain the majority of stellar mass in the universe, and are therefore of special interest in the study of galaxy evolution. The Milky Way (MW) and Andromeda (M31) have present-day stellar masses near M*, at 5 x 10(10) M-circle dot (defined here to be MW-mass) and 10(11) M-circle dot (defined to be M31-mass). We study the typical progenitors of these galaxies using the FOURSTAR Galaxy Evolution Survey (ZFOURGE). ZFOURGE is a deep medium-band near-IR imaging survey, which is sensitive to the progenitors of these galaxies out to z similar to 3. We use abundance-matching techniques to identify the main progenitors of these galaxies at higher redshifts. We measure the evolution in the stellar mass, rest-frame colors, morphologies, far-IR luminosities, and star formation rates, combining our deep multiwavelength imaging with near-IR Hubble Space Telescope imaging from Cosmic Near-IR Deep Extragalactic Legacy Survey (CANDELS), and Spitzer and Herschel far-IR imaging from Great Observatories Origins Deep Survey-Herschel and CANDELS-Herschel. The typical MW-mass and M31-mass progenitors passed through the same evolution stages, evolving from blue, star-forming disk galaxies at the earliest stages to redder dust-obscured IR-luminous galaxies in intermediate stages and to red, more quiescent galaxies at their latest stages. The progenitors of the MW-mass galaxies reached each evolutionary stage at later times (lower redshifts) and with stellar masses that are a factor of two to three lower than the progenitors of the M31-mass galaxies. The process driving this evolution, including the suppression of star formation in present-day M* galaxies, requires an evolving stellar-mass/halo-mass ratio and/or evolving halo-mass threshold for quiescent galaxies. The effective size and SFRs imply that the baryonic cold-gas fractions drop as galaxies evolve from high redshift to z similar to 0 and are strongly anticorrelated with an increase in the Sersic index. Therefore, the growth of galaxy bulges in M* galaxies corresponds to a rapid decline in the galaxy gas fractions and/or a decrease in the star formation efficiency.National Science Foundation AST-1009707, AST-0808133ERC HIGHZ 227749NL-NWO SpinozaNASA NAS5-26555HST program GO-12060National Collaborative Research Infrastructure Strategy of the Australian Federal GovernmentTexas A&M UniversityGeorge P. and Cynthia Woods Institute for Fundamental Physics and AstronomyAstronom

Constraints on the Cosmic Expansion History from GWTC-3

This material is based upon work supported by NSFʼs LIGO Laboratory, which is a major facility fully funded by the National Science Foundation. The authors also gratefully acknowledge the support of the Science and Technology Facilities Council (STFC) of the United Kingdom, the Max-Planck-Society (MPS), and the State of Niedersachsen/Germany for support of the construction of Advanced LIGO and construction and operation of the GEO600 detector. Additional support for Advanced LIGO was provided by the Australian Research Council. The authors gratefully acknowledge the Italian Istituto Nazionale di Fisica Nucleare (INFN), the French Centre National de la Recherche Scientifique (CNRS), and the Netherlands Organization for Scientific Research (NWO), for the construction and operation of the Virgo detector and the creation and support of the EGO consortium. The authors also gratefully acknowledge research support from these agencies as well as by the Council of Scientific and Industrial Research of India, the Department of Science and Technology, India, the Science & Engineering Research Board (SERB), India, the Ministry of Human Resource Development, India, the Spanish Agencia Estatal de Investigación (AEI), the Spanish Ministerio de Ciencia e Innovación and Ministerio de Universidades, the Conselleria de Fons Europeus, Universitat i Cultura and the Direcció General de Política Universitaria i Recerca del Govern de les Illes Balears, the Conselleria d’Innovació Universitats, Ciència i Societat Digital de la Generalitat Valenciana and the CERCA Programme Generalitat de Catalunya, Spain, the National Science Centre of Poland and the European Union–European Regional Development Fund, Foundation for Polish Science (FNP), the Swiss National Science Foundation (SNSF), the Russian Foundation for Basic Research, the Russian Science Foundation, the European Commission, the European Social Funds (ESF), the European Regional Develop- ment Funds (ERDF), the Royal Society, the Scottish Funding Council, the Scottish Universities Physics Alliance, the Hungarian Scientific Research Fund (OTKA), the French Lyon Institute of Origins (LIO), the Belgian Fonds de la Recherche Scientifique (FRS-FNRS), Actions de Recherche Concertées (ARC) and Fonds Wetenschappelijk Onderzoek–Vlaanderen (FWO), Bel- gium, the Paris Île-de-France Region, the National Research, Development and Innovation Office Hungary (NKFIH), the National Research Foundation of Korea, the Natural Science and Engineering Research Council Canada, Canadian Foundation for Innovation (CFI), the Brazilian Ministry of Science, Technology, and Innovations, the International Center for Theoretical Physics South American Institute for Fundamental Research (ICTP- SAIFR), the Research Grants Council of Hong Kong, the National Natural Science Foundation of China (NSFC), the Leverhulme Trust, the Research Corporation, the Ministry of Science and Technology (MOST), Taiwan, the United States Department of Energy, and the Kavli Foundation. The authors gratefully acknowledge the support of the NSF, STFC, INFN, and CNRS for provision of computational resources. This work was supported by MEXT, JSPS Leading-edge Research Infrastructure Program, JSPS Grant-in-Aid for Specially Promoted Research 26000005, JSPS Grant-in-Aid for Scientific Research on Innovative Areas 2905: JP17H06358, JP17H06361, and JP17H06364, JSPS Core-to- Core Program A. Advanced Research Networks, JSPS Grant- in-Aid for Scientific Research (S) 17H06133 and 20H05639, JSPS Grant-in-Aid for Transformative Research Areas (A) 20A203: JP20H05854, the joint research program of the Institute for Cosmic Ray Research, University of Tokyo, National Research Foundation (NRF) and Computing Infra- structure Project of KISTI-GSDC in Korea, Academia Sinica (AS), AS Grid Center (ASGC), and the Ministry of Science and Technology (MoST) in Taiwan under grants including AS- CDA-105-M06, Advanced Technology Center (ATC) of NAOJ, Mechanical Engineering Center of KEK. We would like to thank all of the essential workers who put their health at risk during the COVID-19 pandemic, without whom we would not have been able to complete this work.Peer reviewe