Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks in proton-proton collisions at root s=13TeV

A search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks is performed in proton-proton collisions at a center-of-mass energy of 13 TeV collected with the CMS detector at the LHC. The analyzed data sample corresponds to an integrated luminosity of 35.9 fb(-1). The signal is characterized by a large missing transverse momentum recoiling against a bottom quark-antiquark system that has a large Lorentz boost. The number of events observed in the data is consistent with the standard model background prediction. Results are interpreted in terms of limits both on parameters of the type-2 two-Higgs doublet model extended by an additional light pseudoscalar boson a (2HDM+a) and on parameters of a baryonic Z simplified model. The 2HDM+a model is tested experimentally for the first time. For the baryonic Z model, the presented results constitute the most stringent constraints to date.Peer reviewe

A portrait of the Higgs boson by the CMS experiment ten years after the discovery

A Correction to this paper has been published (18 October 2023) : https://doi.org/10.1038/s41586-023-06164-8.Data availability: Tabulated results are provided in the HEPData record for this analysis. Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS data preservation, re-use and open acess policy.Code availability: The CMS core software is publicly available on GitHub (https://github.com/cms-sw/cmssw).In July 2012, the ATLAS and CMS collaborations at the CERN Large Hadron Collider announced the observation of a Higgs boson at a mass of around 125 gigaelectronvolts. Ten years later, and with the data corresponding to the production of a 30-times larger number of Higgs bosons, we have learnt much more about the properties of the Higgs boson. The CMS experiment has observed the Higgs boson in numerous fermionic and bosonic decay channels, established its spin–parity quantum numbers, determined its mass and measured its production cross-sections in various modes. Here the CMS Collaboration reports the most up-to-date combination of results on the properties of the Higgs boson, including the most stringent limit on the cross-section for the production of a pair of Higgs bosons, on the basis of data from proton–proton collisions at a centre-of-mass energy of 13 teraelectronvolts. Within the uncertainties, all these observations are compatible with the predictions of the standard model of elementary particle physics. Much evidence points to the fact that the standard model is a low-energy approximation of a more comprehensive theory. Several of the standard model issues originate in the sector of Higgs boson physics. An order of magnitude larger number of Higgs bosons, expected to be examined over the next 15 years, will help deepen our understanding of this crucial sector.BMBWF and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, FAPERGS, and FAPESP (Brazil); MES and BNSF (Bulgaria); CERN; CAS, MoST, and NSFC (China); MINCIENCIAS (Colombia); MSES and CSF (Croatia); RIF (Cyprus); SENESCYT (Ecuador); MoER, ERC PUT and ERDF (Estonia); Academy of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRI (Greece); NKFIH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); MSIP and NRF (Republic of Korea); MES (Latvia); LAS (Lithuania); MOE and UM (Malaysia); BUAP, CINVESTAV, CONACYT, LNS, SEP, and UASLP-FAI (Mexico); MOS (Montenegro); MBIE (New Zealand); PAEC (Pakistan); MES and NSC (Poland); FCT (Portugal); MESTD (Serbia); MCIN/AEI and PCTI (Spain); MOSTR (Sri Lanka); Swiss Funding Agencies (Switzerland); MST (Taipei); MHESI and NSTDA (Thailand); TUBITAK and TENMAK (Turkey); NASU (Ukraine); STFC (United Kingdom); DOE and NSF (USA). Individuals have received support from the Marie-Curie programme and the European Research Council and Horizon 2020 Grant, contract Nos. 675440, 724704, 752730, 758316, 765710, 824093, 884104, and COST Action CA16108 (European Union); the Leventis Foundation; the Alfred P. Sloan Foundation; the Alexander von Humboldt Foundation; the Belgian Federal Science Policy Office; the Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture (FRIA-Belgium); the Agentschap voor Innovatie door Wetenschap en Technologie (IWT-Belgium); the F.R.S.-FNRS and FWO (Belgium) under the “Excellence of Science – EOS” – be.h project n. 30820817; the Beijing Municipal Science & Technology Commission, No. Z191100007219010; the Ministry of Education, Youth and Sports (MEYS) of the Czech Republic; the Stavros Niarchos Foundation (Greece); the Deutsche Forschungsgemeinschaft (DFG), under Germany’s Excellence Strategy – EXC 2121 “Quantum Universe” – 390833306, and under project number 400140256 - GRK2497; the Hungarian Academy of Sciences, the New National Excellence Program - ÚNKP, the NKFIH research grants K 124845, K 124850, K 128713, K 128786, K 129058, K 131991, K 133046, K 138136, K 143460, K 143477, 2020-2.2.1-ED-2021-00181, and TKP2021-NKTA-64 (Hungary); the Council of Science and Industrial Research, India; the Latvian Council of Science; the Ministry of Education and Science, project no. 2022/WK/14, and the National Science Center, contracts Opus 2021/41/B/ST2/01369 and 2021/43/B/ST2/01552 (Poland); the Fundação para a Ciência e a Tecnologia, grant CEECIND/01334/2018 (Portugal); the National Priorities Research Program by Qatar National Research Fund; MCIN/AEI/10.13039/501100011033, ERDF “a way of making Europe”, and the Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia María de Maeztu, grant MDM-2017-0765 and Programa Severo Ochoa del Principado de Asturias (Spain); the Chulalongkorn Academic into Its 2nd Century Project Advancement Project, and the National Science, Research and Innovation Fund via the Program Management Unit for Human Resources & Institutional Development, Research and Innovation, grant B05F650021 (Thailand); the Kavli Foundation; the Nvidia Corporation; the SuperMicro Corporation; the Welch Foundation, contract C-1845; and the Weston Havens Foundation (USA)

Measurement of the differential tt¯ production cross section as a function of the jet mass and extraction of the top quark mass in hadronic decays of boosted top quarks

Data Availability: This manuscript has no associated data or the data will not be deposited. [Authors’ comment: Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in https://cms-docdb.cern.ch/cgibin/PublicDocDB/RetrieveFile?docid=6032 &filename=CMSDataPolicyV1.2.pdf &version=2.]A measurement of the jet mass distribution in hadronic decays of Lorentz-boosted top quarks is presented. The measurement is performed in the lepton + jets channel of top quark pair production (tt¯ ) events, where the lepton is an electron or muon. The products of the hadronic top quark decay are reconstructed using a single large-radius jet with transverse momentum greater than 400GeV . The data were collected with the CMS detector at the LHC in proton-proton collisions and correspond to an integrated luminosity of 138fb−1 . The differential tt¯ production cross section as a function of the jet mass is unfolded to the particle level and is used to extract the top quark mass. The jet mass scale is calibrated using the hadronic W boson decay within the large-radius jet. The uncertainties in the modelling of the final state radiation are reduced by studying angular correlations in the jet substructure. These developments lead to a significant increase in precision, and a top quark mass of 173.06±0.84GeV.SCOAP

Search for low-mass dilepton resonances in Higgs boson decays to four-lepton final states in proton–proton collisions at √s=13TeV

Data Availability: This manuscript has no associated data or the data will not be deposited. [Authors’ comment: For CMS Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in “CMS data preservation, re-use and open access policy” (https://cms-docdb.cern.ch/cgi-bin/PublicDocDB/RetrieveFile?docid=6032&filename=CMSDataPolicyV1.2.pdf&version=2).]Copyright © CERN for the benefit of the CMS collaboration 2022. A search for low-mass dilepton resonances in Higgs boson decays is conducted in the four-lepton final state. The decay is assumed to proceed via a pair of beyond the standard model particles, or one such particle and a Z boson. The search uses proton–proton collision data collected with the CMS detector at the CERN LHC, corresponding to an integrated luminosity of 137fb−1, at a center-of-mass energy s√=13TeV. No significant deviation from the standard model expectation is observed. Upper limits at 95% confidence level are set on model-independent Higgs boson decay branching fractions. Additionally, limits on dark photon and axion-like particle production, based on two specific models, are reported.SCOAP3

Search for dark matter produced in association with a leptonically decaying Z boson in proton–proton collisions at s√=13TeV

A search for dark matter particles is performed using events with a Z boson candidate and large missing transverse momentum. The analysis is based on proton–proton collision data at a center-of-mass energy of 13TeV, collected by the CMS experiment at the LHC in 2016–2018, corresponding to an integrated luminosity of 137fb−1. The search uses the decay channels Z→ee and Z→μμ. No significant excess of events is observed over the background expected from the standard model. Limits are set on dark matter particle production in the context of simplified models with vector, axial-vector, scalar, and pseudoscalar mediators, as well as on a two-Higgs-doublet model with an additional pseudoscalar mediator. In addition, limits are provided for spin-dependent and spin-independent scattering cross sections and are compared to those from direct-detection experiments. The results are also interpreted in the context of models of invisible Higgs boson decays, unparticles, and large extra dimensions.SCOAP

Measurements of pp → ZZ production cross sections and constraints on anomalous triple gauge couplings at √ = 13 TeV

© 2021 The CMS Collaboration. The production of Z boson pairs in proton–proton (pp) collisions, pp → (Z/∗)(Z/∗) → 2ℓ2ℓ′, where ℓ,ℓ′ = e or μ, is studied at a center-of-mass energy of 13 TeV with the CMS detector at the CERN LHC. The data sample corresponds to an integrated luminosity of 137fb−1, collected during 2016–2018. The ZZ production cross section, tot(pp → ZZ) = 17.4 ± 0.3 (stat) ± 0.5 (syst) ± 0.4 (Theo) ± 0.3 (lumi) pb, measured for events with two pairs of opposite-sign, same-flavor leptons produced in the mass region 60 < ℓ+ℓ− < 120 GeV is consistent with standard model predictions. Differential cross sections are also measured and agree with theoretical predictions. The invariant mass distribution of the four-lepton system is used to set limits on anomalous ZZZ and ZZ couplings.SCOAP