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Infants with congenital hyperinsulinism owing to inactivating mutations in the K(ATP) channel (K(ATP)HI) who are unresponsive to medical therapy will require pancreatectomy to control the hypoglycemia. In preclinical studies, we showed that the GLP-1 receptor antagonist exendin-(9-39) suppresses insulin secretion and corrects fasting hypoglycemia in SUR-1(-/-) mice. The aim of this study was to examine the effects of exendin-(9-39) on fasting blood glucose in subjects with K(ATP)HI. This was a randomized, open-label, two-period crossover pilot clinical study. Nine subjects with K(ATP)HI received either exendin-(9-39) or vehicle on two different days. The primary outcome was blood glucose; secondary outcomes were insulin, glucagon, and GLP-1. In all subjects, mean nadir blood glucose and glucose area under the curve were significantly increased by exendin-(9-39). Insulin-to-glucose ratios were significantly lower during exendin-(9-39) infusion compared with vehicle. Fasting glucagon and intact GLP-1 were not affected by treatment. In addition, exendin-(9-39) significantly inhibited amino acid-stimulated insulin secretion in pancreatic islets isolated from neonates with K(ATP)HI. Our findings have two important implications: 1) GLP-1 and its receptor play a role in the regulation of fasting glycemia in K(ATP)HI; and 2) the GLP-1 receptor may be a therapeutic target for the treatment of children with K(ATP)HI.

Context: Mutations in hepatocyte nuclear factor 1B ( HNF1B ) are rare but they are known to cause structural renal disease and diabetes mellitus. There is limited data on pediatric HNF1B disease. Objective: To analyze the clinical characteristics of HNF1B ‐related disease in a cohort of children identified at a single pediatric tertiary medical center, with a specific focus on endocrine‐related disease. Methods: Subjects with HNF1B genetic variants were identified from the Children’s Hospital of Philadelphia Atypical Diabetes Registry between 2013 and 2022. Results: Of the 11 pediatric subjects with HNF1B mutations or deletions, 7 (64%) initially presented with diabetes, sometimes referred to as MODY5, while 4 (36%) were diagnosed based on family history or a genetic evaluation of renal disease. Only one patient presented with diabetic ketoacidosis, and three presented with diabetic ketosis. Of the four children with HNF1B mutations identified by familial mutation analysis or based on renal disease, two developed diabetes during the course of the study. Abnormalities in fasting lipid profiles were common: 10 with triglycerides >90 mg/dL, 5 with LDL‐C >110 mg/dL, 5 with HDL‐C <45, and 7/11 with non‐HDL cholesterol >120 mg/dL. Over half of the subjects had hyperparathyroidism with PTH (>65 pg/mL) and a calcium concentration >9 mg/dL. Conclusion: This case series represents one of the largest pediatric HNF1B ‐related disease cohorts at a single center. The majority of patients with diabetes presented with clinical features distinct from Type 1 or Type 2 diabetes. Pediatricians should consider genetic testing for HNF1B mutations when children are diagnosed with diabetes and have renal abnormalities, hyperlipidemia, and hyperparathyroidism.

In this paper, we propose a Four-Dimensional Variational (4D-Var) data assimilation framework for wind energy potential estimation. The framework is defined as follows: we choose a numerical model which can provide forecasts of wind speeds then, an ensemble of model realizations is employed to build control spaces at observation steps via a modified Cholesky decomposition. These control spaces are utilized to estimate initial analysis increments and to avoid the intrinsic use of adjoint models in the 4D-Var context. The initial analysis increments are mapped back onto the model domain from which we obtain an estimate of the initial analysis ensemble. This ensemble is propagated in time to approximate the optimal analysis trajectory. Wind components are post-processed to get wind speeds and to estimate wind energy capacities. A matrix-free analysis step is derived from avoiding the direct inversion of covariance matrices during assimilation cycles. Numerical simulations are employed to illustrate how our proposed framework can be employed in operational scenarios. A catalogue of twelve Wind Turbine Generators (WTGs) is utilized during the experiments. The results reveal that our proposed framework can properly estimate wind energy potential capacities for all wind turbines within reasonable accuracies (in terms of Root-Mean-Square-Error) and even more, these estimations are better than those of traditional 4D-Var ensemble-based methods. Moreover, large variability (variance of standard deviations) of errors are evidenced in forecasts of wind turbines with the largest rate-capacity while homogeneous variability can be seen in wind turbines with the lowest rate-capacity.

PurposeDisaster management agencies are mandated to reduce risk for the populations that they serve. Yet, inequities in how they function may result in their activities creating disaster risk, particularly for already vulnerable and marginalized populations. In this article, how disaster management agencies create disaster risk for vulnerable and marginalized groups is examined, seeking to show the ways existing policies affect communities, and provide recommendations on policy and future research.Design/methodology/approachThe authors undertook a systematic review of the US disaster management agency, Federal Emergency Management Agency (FEMA), examining its programs through a lens of equity to understand how they shape disaster risk.FindingsDespite a growing commitment to equity within FEMA, procedural, distributive, and contextual inequities result in interventions that perpetuate and amplify disaster risk for vulnerable and marginalized populations. Some of these inequities could be remediated by shifting toward a more bottom-up approach to disaster management, such as community-based disaster risk reduction approaches.Practical implicationsDisaster management agencies and other organizations can use the results of this study to better understand how to devise interventions in ways that limit risk creation for vulnerable populations, including through community-based approaches.Originality/valueThis study is the first to examine disaster risk creation from an organizational perspective, and the first to focus explicitly on how disaster management agencies can shape risk creation. This helps understand the linkages between disaster risk creation, equity and organizations.

The CMS Collaboration plans to equip the very forward muon system with triple-GEM detectors that can withstand the environment of the High-Luminosity LHC. This project is at the final stages of R&D and moving to production. An unprecedented large area of several 100 m 2 are to be instrumented with GEM detectors which will be produced in six different sites around the world. A common construction and quality control procedure is required to ensure the performance of each detector. The quality control steps will include optical inspection, cleaning and baking of all materials and parts used to build the detector, leakage current tests of the GEM foils, high voltage tests, gas leak tests of the chambers and monitoring pressure drop vs. time, gain calibration to know the optimal operation region of the detector, gain uniformity tests, and studying the efficiency, noise and tracking performance of the detectors in a cosmic stand using scintillators.

Infants with congenital hyperinsulinism owing to inactivating mutations in the [K.sub.ATP] channel ([K.sub.ATP]HI) who are unresponsive to medical therapy will require pancreatectomy to control the hypoglycemia. In preclinical studies, we showed that the GLP-1 receptor antagonist exendin-(9-39) suppresses insulin secretion and corrects fasting hypoglycemia in [SUR.sup.1-/-] mice. The aim of this study was to examine the effects of exendin-(9-39) on fasting blood glucose in subjects with [K.sub.ATP]HI. This was a randomized, open-label, two-period crossover pilot clinical study. Nine subjects with [K.sub.ATP]HI received either exendin-(9-39) or vehicle on two different days. The primary outcome was blood glucose; secondary outcomes were insulin, glucagon, and GLP-1. In all subjects, mean nadir blood glucose and glucose area under the curve were significantly increased by exendin-(9-39). Insulin-to-glucose ratios were significantly lower during exendin-(9-39) infusion compared with vehicle. Fasting glucagon and intact GLP-1 were not affected by treatment. In addition, exendin-(9-39) significantly inhibited amino acid-stimulated insulin secretion in pancreatic islets isolated from neonates with [K.sub.ATP]HI. Our findings have two important implications: 1) GLP-1 and its receptor play a role in the regulation of fasting glycemia in [K.sub.ATP]HI; and 2) the GLP-1 receptor may be a therapeutic target for the treatment of children with [K.sub.ATP]HI.

The dependence of inclusive jet production in proton-proton collisions with a center-of-mass energy of 13 TeV on the distance parameter R of the anti- k T algorithm is studied using data corresponding to integrated luminosities up to 35.9 fb − 1 collected by the CMS experiment in 2016. The ratios of the inclusive cross sections as functions of transverse momentum p T and rapidity y , for R in the range 0.1 to 1.2 to those using R = 0 . 4 are presented in the region 84 < p T < 1588 GeV and | y | < 2 . 0. The results are compared to calculations at leading and next-to-leading order in the strong coupling constant using different parton shower models. The variation of the ratio of cross sections with R is well described by calculations including a parton shower model, but not by a leading-order quantum chromodynamics calculation including nonperturbative effects. The agreement between the data and the theoretical predictions for the ratios of cross sections is significantly improved when next-to-leading order calculations with nonperturbative effects are used.

A search is presented for additional scalar (H) or pseudoscalar (A) Higgs bosons decaying to a top quark pair in proton-proton collisions at a center-of-mass energy of 13 TeV. The data set analyzed corresponds to an integrated luminosity of 35.9 fb − 1 collected by the CMS experiment at the LHC. Final states with one or two charged leptons are considered. The invariant mass of the reconstructed top quark pair system and variables that are sensitive to the spin of the particles decaying into the top quark pair are used to search for signatures of the H or A bosons. The interference with the standard model top quark pair background is taken into account. A moderate signal-like deviation compatible with an A boson with a mass of 400 GeV is observed with a global significance of 1.9 standard deviations. New stringent constraints are reported on the strength of the coupling of the hypothetical bosons to the top quark, with the mass of the bosons ranging from 400 to 750 GeV and their total relative width from 0.5 to 25%. The results of the search are also interpreted in a minimal supersymmetric standard model scenario. Values of m A from 400 to 700 GeV are probed, and a region with values of tan β below 1.0 to 1.5, depending on m A , is excluded at 95% confidence level.

A data sample of events from proton-proton collisions with at least two jets, and two isolated same-sign or three or more charged leptons, is studied in a search for signatures of new physics phenomena. The data correspond to an integrated luminosity of 137 \\text fb⁻¹ 137fb-1 at a center-of-mass energy of 13 \\text TeV 13TeV, collected in 2016–2018 by the CMS experiment at the LHC. The search is performed using a total of 168 signal regions defined using several kinematic variables. The properties of the events are found to be consistent with the expectations from standard model processes. Exclusion limits at 95% confidence level are set on cross sections for the pair production of gluinos or squarks for various decay scenarios in the context of supersymmetric models conserving or violating R parity. The observed lower mass limits are as large as 2.1 \\text TeV 2.1TeV for gluinos and 0.9 \\text TeV 0.9TeV for top and bottom squarks. To facilitate reinterpretations, model-independent limits are provided in a set of simplified signal regions.

This paper reports on a search for an extension to the scalar sector of the standard model, where a new CP-even (odd) boson decays to a Z boson and a lighter CP-odd (even) boson, and the latter further decays to a b quark pair. The Z boson is reconstructed via its decays to electron or muon pairs. The analysed data were recorded in proton-proton collisions at a center-of-mass energy$$ \\sqrt{s} $$s = 13 TeV, collected by the CMS experiment at the LHC during 2016, corresponding to an integrated luminosity of 35.9 fb − 1 . Data and predictions from the standard model are in agreement within the uncertainties. Upper limits at 95% confidence level are set on the production cross section times branching fraction, with masses of the new bosons up to 1000 GeV. The results are interpreted in the context of the two-Higgs-doublet model.