Highly diastereoselective synthesis of substituted pyrrolidines using a sequence of azomethine ylide cycloaddition and nucleophilic cyclization

Abstract: Although cycloadditions of azomethine ylides usually give mixtures of endo/exo adducts, we successfully tuned the mechanistic path of a new reaction cascade to afford substituted pyrrolidines in high yields and diastereomeric purity. This was achieved by forcing the demetalation of tin- or silicon-substituted iminium ions, followed by azomethine ylide cycloaddition and nucleophilic cyclization. Structural complexity is thus built rapidly in a fully controlled one-pot reaction cascade

Pancreas exocrine replacement therapy is associated with increased survival following pancreatoduodenectomy for periampullary malignancy

Background: Although many patients undergoing pancreatoduodenectomy (PD) for cancer have pancreatic exocrine insufficiency, pancreatic enzyme replacement therapy (PERT) is not routinely used, and effects upon post-operative survival are unclear.Methods: This review of patients undergoing PD for periampullary malignancy sought to test for an association between PERT and overall survival, with post-hoc subgroup analysis performed after stratifying patients by the year of surgery, pancreatic duct width and tumour type.Results: Some 202/469 (43.1%) patients received PERT. After accounting for pathological variables and chemotherapy, PERT use was found to be independently associated with improved survival on multivariable analysis [HR 0.72 (95% CI: 0.52-0.99), p = 0.044] and on propensity matched analysis (p = 0.009). The effect of PERT upon improved survival was predominantly observed amongst patients with a dilated pancreatic duct (>= 3 mm).Discussion: PERT use was independently associated with improved survival following PD for cancer. The validity of this observation is supported by an effect largely confined to those patients with a dilated pancreatic duct. The nutritional status of patients undergoing PD for cancer needs further investigation and the effects of PERT require verification in further clinical studies

A Versatile cascade of intramolecular vilsmeier-haack and azomethine ylide 1,3-dipolar cycloaddition toward tricyclic cores of alkaloids

Abstract: In the pursuit of synthetic efficiency, we developed an innovative one-pot transformation of linear substrates into bi- and tricyclic adducts using a cascade of amide activation, nucleophilic cyclization, azomethine ylide generation, and subsequent inter- or intramolecular 1,3-dipolar cycloaddition. Despite the high density and variety of functional groups on the substrates, the sequence occurred with perfect chemoselectivity with good to excellent yields

Measurements of Higgs boson production cross sections and couplings in the diphoton decay channel at s=\sqrt{s} = 13 TeV

A preprint version of the article is available at ArXiv (https://arxiv.org/abs/2103.06956).© 2021 The Author(s). Measurements of Higgs boson production cross sections and couplings in events where the Higgs boson decays into a pair of photons are reported. Events are selected from a sample of proton-proton collisions at $\sqrt{s}=$ 13 TeV collected by the CMS detector at the LHC from 2016 to 2018, corresponding to an integrated luminosity of 137 fb$^{-1}$. Analysis categories enriched in Higgs boson events produced via gluon fusion, vector boson fusion, vector boson associated production, and production associated with top quarks are constructed. The total Higgs boson signal strength, relative to the standard model (SM) prediction, is measured to be 1.12$\pm$0.09. Other properties of the Higgs boson are measured, including SM signal strength modifiers, production cross sections, and its couplings to other particles. These include the most precise measurements of gluon fusion and vector boson fusion Higgs boson production in several different kinematic regions, the first measurement of Higgs boson production in association with a top quark pair in five regions of the Higgs boson transverse momentum, and an upper limit on the rate of Higgs boson production in association with a single top quark. All results are found to be in agreement with the SM expectations.SCOAP

Measurement of differential t¯t production cross sections in the full kinematic range using lepton + jets events from proton-proton collisions at ffiffi s p = 13 TeV

CERN, for the CMS CollaborationCopyright © 2021 CERN, for the CMS Collaboration. Measurements of differential and double-differential cross sections of top-quark pair (tt¯) production are presented in the lepton+jets channels with a single electron or muon and jets in the final state. The analysis combines for the first time signatures of top quarks with low transverse momentum pT, where the top-quark decay products can be identified as separated jets and isolated leptons, and with high pT, where the decay products are collimated and overlap. The measurements are based on proton-proton collision data at s=13 TeV collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 137 fb-1. The cross sections are presented at the parton and particle levels, where the latter minimizes extrapolations based on theoretical assumptions. Most of the measured differential cross sections are well described by standard model predictions with the exception of some double-differential distributions. The inclusive tt¯ production cross section is measured to be σtt¯=791±25 pb, which constitutes the most precise measurement in the lepton+jets channel to date.Funded by SCOA

Diarrhea, Pneumonia, and Infectious Disease Mortality in Children Aged 5 to 14 Years in India

Background: Little is known about the causes of death in children in India after age five years. The objective of this study is to provide the first ever direct national and sub-national estimates of infectious disease mortality in Indian children aged 5 to 14 years. Methods: A verbal autopsy based assessment of 3 855 deaths is children aged 5 to 14 years from a nationally representative survey of deaths occurring in 2001–03 in 1?1 million homes in India. Results: Infectious diseases accounted for 58 % of all deaths among children aged 5 to 14 years. About 18 % of deaths were due to diarrheal diseases, 10 % due to pneumonia, 8 % due to central nervous system infections, 4 % due to measles, and 12 % due to other infectious diseases. Nationally, in 2005 about 59 000 and 34 000 children aged 5 to 14 years died from diarrheal diseases and pneumonia, corresponding to mortality of 24?1 and 13?9 per 100 000 respectively. Mortality was nearly 50 % higher in girls than in boys for both diarrheal diseases and pneumonia. Conclusions: Approximately 60 % of all deaths in this age group are due to infectious diseases and nearly half of these deaths are due to diarrheal diseases and pneumonia. Mortality in this age group from infectious diseases, and diarrhea i

Isoflavone metabolism in domestic cats (Felis catus): comparison of plasma metabolites detected after ingestion of two different dietary forms of genistein and daidzein

Some felid diets contain isoflavones but the metabolic capacity of cats toward isoflavones is relatively unknown, despite the understanding that isoflavones have divergent biological potential according to their metabolite end products. The objective of this study was to determine the plasma metabolites detectable in domestic cats after exposure to 2 different dietary forms of isoflavones, either as a soy extract tablet ( n = 6) or as part of a dietary matrix ( n = 4). Serial blood samples were collected after isoflavone exposure to identify the plasma metabolites of each cat. Genistein was detected in its unconjugated form or as a monosulfate. Daidzein was detected as both a mono- and disulfate as well as in its unconjugated form. Other daidzein metabolites detected included equol mono- and disulfate, dihydrodaidzein, and O -desmethylangolensin. No β -glucuronide metabolites of either isoflavone were detected. Equol was produced in markedly fewer cats after ingestion of a soy extract tablet as a single oral bolus compared with cats consuming an isoflavone-containing diet. The detectable metabolites of the isoflavones, genistein and daidzein, in domestic cat plasma after dietary ingestion has been described in the present study for the first time. The metabolic capacity for isoflavones by domestic cats appears to be efficient, with only minimal proportions of the ingested amount detected in their unconjugated forms. This has implications for the potential of isoflavones to exert physiological activity in the domestic cat when consumed at concentrations representative of typical dietary intake

Stuart Warren (24 Dec 1938–22 Mar 2020)

Celebrating the life of Stuart Warren

Performance of InterVA for assigning causes of death to verbal autopsies: multisite validation study using clinical diagnostic gold standards

Background: InterVA is a widely disseminated tool for cause of death attribution using information from verbal autopsies. Several studies have attempted to validate the concordance and accuracy of the tool, but the main limitation of these studies is that they compare cause of death as ascertained through hospital record review or hospital discharge diagnosis with the results of InterVA. This study provides a unique opportunity to assess the performance of InterVA compared to physician-certified verbal autopsies (PCVA) and alternative automated methods for analysis.Methods: Using clinical diagnostic gold standards to select 12,542 verbal autopsy cases, we assessed the performance of InterVA on both an individual and population level and compared the results to PCVA, conducting analyses separately for adults, children, and neonates. Following the recommendation of Murray et al., we randomly varied the cause composition over 500 test datasets to understand the performance of the tool in different settings. We also contrasted InterVA with an alternative Bayesian method, Simplified Symptom Pattern (SSP), to understand the strengths and weaknesses of the tool.Results: Across all age groups, InterVA performs worse than PCVA, both on an individual and population level. On an individual level, InterVA achieved a chance-corrected concordance of 24.2% for adults, 24.9% for children, and 6.3% for neonates (excluding free text, considering one cause selection). On a population level, InterVA achieved a cause-specific mortality fraction accuracy of 0.546 for adults, 0.504 for children, and 0.404 for neonates. The comparison to SSP revealed four specific characteristics that lead to superior performance of SSP. Increases in chance-corrected concordance are attained by developing cause-by-cause models (2%), using all items as opposed to only the ones that mapped to InterVA items (7%), assigning probabilities to clusters of symptoms (6%), and using empirical as opposed to expert probabilities (up to 8%).Conclusions: Given the widespread use of verbal autopsy for understanding the burden of disease and for setting health intervention priorities in areas that lack reliable vital registrations systems, accurate analysis of verbal autopsies is essential. While InterVA is an affordable and available mechanism for assigning causes of death using verbal autopsies, users should be aware of its suboptimal performance relative to other methods

Cause-of-death ascertainment for deaths that occur outside hospitals in Thailand: application of verbal autopsy methods

Background: Ascertainment of cause for deaths that occur in the absence of medical attention is a significant problem in many countries, including Thailand, where more than 50% of such deaths are registered with ill-defined causes. Routine implementation of standardized, rigorous verbal autopsy methods is a potential solution. This paper reports findings from field research conducted to develop, test, and validate the use of verbal autopsy (VA) methods in Thailand.Methods: International verbal autopsy methods were first adapted to the Thai context and then implemented to ascertain causes of death for a nationally representative sample of 11,984 deaths that occurred in Thailand in 2005. Causes of death were derived from completed VA questionnaires by physicians trained in ICD-based cause-of-death certification. VA diagnoses were validated in the sample of hospital deaths for which reference diagnoses were available from medical record review. Validated study findings were used to adjust VA-based causes of death derived for deaths in the study sample that had occurred outside hospitals. Results were used to estimate cause-specific mortality patterns for deaths outside hospitals in Thailand in 2005.Results: VA-based causes of death were derived for 6,328 out of 7,340 deaths in the study sample that had occurred outside hospitals, constituting the verification arm of the study. The use of VA resulted in large-scale reassignment of deaths from ill-defined categories to specific causes of death. The validation study identified that VA tends to overdiagnose important causes such as diabetes, liver cancer, and tuberculosis, while undercounting deaths from HIV/AIDS, liver diseases, genitourinary (essential renal), and digestive system disorders.Conclusions: The use of standard VA methods adapted to Thailand enabled a plausible assessment of cause-specific mortality patterns and a substantial reduction of ill-defined diagnoses. Validation studies enhance the utility of findings from the application of verbal autopsy. Regular implementation of VA in Thailand could accelerate development of the quality and utility of vital registration data for deaths outside hospitals