Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Precison Measurements of the Mass, the Widths of ψ(3770)\psi(3770) Resonance and the Cross Section σ[e+e−→ψ(3770)]\sigma[e^+e^-\to \psi(3770)] at Ecm=3.7724E_{\rm cm}=3.7724 GeV

By analyzing the $R$ values measured at 68 energy points in the energy region between 3.650 and 3.872 GeV reported in our previous paper, we have precisely measured the mass, the total width, the leptonic width and the leptonic decay branching fraction of the $\psi(3770)$ to be ${M}_{\psi(3770)}=3772.4 \pm 0.4 \pm 0.3$ MeV, $\Gamma_{\psi(3770)}^{\rm tot} = 28.6 \pm 1.2 \pm 0.2$ MeV, $\Gamma_{\psi(3770)}^{ee} = 279 \pm 11 \pm 13$ eV and $B[\psi(3770)\to e^+e^-]=(0.98\pm 0.04\pm 0.04)\times 10^{-5}$, respectively, which result in the observed cross section $\sigma^{\rm obs}[e^+e^-\to \psi(3770)]=7.25\pm 0.27 \pm 0.34$ nb at $\sqrt{s}=3772.4$ MeV. We have also measured $R_{\rm uds}=2.121\pm 0.023 \pm 0.084$ for the continuum light hadron production in the region from 3.650 to 3.872 GeV.Comment: 5 pages, 2 figure

Measurement of \chi_cJ--> K+K-K+K-

Using 14M psi(2S) events taken with the BES-II detector, chi_cJ-->K+K-K+K- decays are studied. For the four-kaon final state, the branching fractions are B(chi_c0,1,2 -->K+K-K+K-)=(3.48\pm 0.23\pm 0.47)\times 10^{-3}, (0.70\pm 0.13\pm 0.10)\times 10^{-3}, and (2.17\pm 0.20\pm 0.31)\times 10^{-3}. For the \phi K+K- final state, the branching fractions, which are measured for the first time, are B(chi_c0,1,2-->\phi K+K-)=(1.03\pm 0.22\pm 0.15)\times 10^{-3}, (0.46\pm 0.16\pm 0.06)\times 10^{-3}, and (1.67\pm 0.26\pm 0.24)\times 10^{-4}. For the \phi\phi final state, B(chi_{c0,2}-->\phi\phi)=(0.94\pm 0.21\pm 0.13)\times 10^{-3} and (1.70\pm 0.30\pm 0.25)\times 10^{-3}.Comment: 7 pages, 7 figure