Rare Pathogenic Copy Number Variation in the 16p11.2 (BP4–BP5) Region Associated with Neurodevelopmental and Neuropsychiatric Disorders: A Review of the Literature

Copy number variants (CNVs) play an important role in the genetic underpinnings of neuropsychiatric/neurodevelopmental disorders. The chromosomal region 16p11.2 (BP4-BP5) harbours both deletions and duplications that are associated in carriers with neurodevelopmental and neuropsychiatric conditions as well as several rare disorders including congenital malformation syndromes. The aim of this article is to provide a review of the current knowledge of the diverse neurodevelopmental disorders (NDD) associated with 16p11.2 deletions and duplications reported in published cohorts. A literature review was conducted using the PubMed/MEDLINE electronic database limited to papers published in English between 1 January 2010 and 31 July 2020, describing 16p11.2 deletions and duplications carriers' cohorts. Twelve articles meeting inclusion criteria were reviewed from the 75 articles identified by the search. Of these twelve papers, eight described both deletions and duplications, three described deletions only and one described duplications only. This study highlights the heterogeneity of NDD descriptions of the selected cohorts and inconsistencies concerning accuracy of data reporting.info:eu-repo/semantics/publishedVersio

Contrasting responses of mean and extreme snowfall to climate change

Snowfall is an important element of the climate system, and one that is expected to change in a warming climate. Both mean snowfall and the intensity distribution of snowfall are important, with heavy snowfall events having particularly large economic and human impacts. Simulations with climate models indicate that annual mean snowfall declines with warming in most regions but increases in regions with very low surface temperatures. The response of heavy snowfall events to a changing climate, however, is unclear. Here I show that in simulations with climate models under a scenario of high emissions of greenhouse gases, by the late twenty-first century there are smaller fractional changes in the intensities of daily snowfall extremes than in mean snowfall over many Northern Hemisphere land regions. For example, for monthly climatological temperatures just below freezing and surface elevations below 1,000 metres, the 99.99th percentile of daily snowfall decreases by 8% in the multimodel median, compared to a 65% reduction in mean snowfall. Both mean and extreme snowfall must decrease for a sufficiently large warming, but the climatological temperature above which snowfall extremes decrease with warming in the simulations is as high as −9 °C, compared to −14 °C for mean snowfall. These results are supported by a physically based theory that is consistent with the observed rain–snow transition. According to the theory, snowfall extremes occur near an optimal temperature that is insensitive to climate warming, and this results in smaller fractional changes for higher percentiles of daily snowfall. The simulated changes in snowfall that I find would influence surface snow and its hazards; these changes also suggest that it may be difficult to detect a regional climate-change signal in snowfall extremes.National Science Foundation (U.S.) (Grant AGS-1148594)United States. National Aeronautics and Space Administration (ROSES Grant 09-IDS09-0049

Defining levels of care in cardiogenic shock

BackgroundExpert opinion and professional society statements have called for multi-tier care systems for the management of cardiogenic shock (CS). However, little is known about how to pragmatically define centers with different levels of care (LOC) for CS.MethodsEleven of 23 hospitals within our healthcare system sharing a common electronic health record were classified as different LOC according to their highest mechanical circulatory support (MCS) capabilities: Level 1 (L-1)—durable left ventricular assist device, Level 1A (L-1A)—extracorporeal membrane oxygenation, Level 2 (L-2)—intra-aortic balloon pump and percutaneous ventricular assist device; and Level 3 (L-3)—no MCS. All adult patients treated for CS (International Classification of Diseases, ICD-10 code R57.0) between 2016 and 2022 were included. Etiologies of CS were identified using associated diagnostic codes. Management strategies and outcomes across LOC were compared.ResultsHigher LOC centers had higher volumes: L-1 (n = 1): 2,831 patients, L-1A (n = 4): 3,452, L-2 (n = 1): 340, and L-3 (n = 5): 780. Emergency room admissions were more common in lower LOC (96% at L-3 vs. 46% L-1; p < 0.001), while hospital transfers were predominant at higher LOC (40% at L-1 vs. 2.7% at L-3; p < 0.001). Men comprised 61% of the cohort. Patients were younger in the higher LOC [69 (60–78) years at L-1 vs. 77 (67–85) years at L-3; p < 0.001]. Patients with acute myocardial infarction (AMI)-CS and acute heart failure (AHF)-CS were concentrated in higher LOC centers while other etiologies of CS were more common in L-2 and L-3 (p < 0.001). Cardiac arrest on admission was more prevalent in lower LOC centers (L-1: 2.8% vs. L-3: 12.1%; p < 0.001). Patients with AMI-CS received more percutaneous coronary intervention in lower LOC (51% L-2 vs. 29% L-1; p < 0.01) but more coronary arterial bypass graft surgery at higher LOC (L-1: 42% vs. L-1A: 23%; p < 0.001). MCS use was consistent across levels for AMI-CS but was more frequent in higher LOC for AHF-CS patients (L-1: 28% vs. L-2: 10%; p < 0.001). Despite increasing in-hospital mortality with decreasing LOC, no significant difference was seen after multivariable adjustment.ConclusionThis is the first report describing a pragmatic classification of LOC for CS which, based on MCS capabilities, can discriminate between centers with distinct demographics, practice patterns, and outcomes. This classification may serve as the basis for future research and the creation of CS systems of care

Major merging history in CANDELS. I. Evolution of the incidence of massive galaxy–galaxy pairs from z = 3 to z ∼ 0

The rate of major galaxy–galaxy merging is theoretically predicted to steadily increase with redshift during the peak epoch of massive galaxy development (1 ≤ z ≤ 3). We use close-pair statistics to objectively study the incidence of massive galaxies (stellar M1 > 2 × 1010 M⊙) hosting major companions (1 ≤ M1/M2 ≤ 4; i.e. 4:1) companions at z > 1. We show that these evolutionary trends are statistically robust to changes in companion proximity. We find disagreements between published results are resolved when selection criteria are closely matched. If we compute merger rates using constant fraction-to-rate conversion factors (Cmerg,pair = 0.6 and Tobs,pair = 0.65 Gyr), we find that MR rates disagree with theoretical predictions at z > 1.5. Instead, if we use an evolving Tobs,pair(z) ∝ (1 + z)−2 from Snyder et al., our MR-based rates agree with theory at 0 < z < 3. Our analysis underscores the need for detailed calibration of Cmerg,pair and Tobs,pair as a function of redshift, mass, and companion selection criteria to better constrain the empirical major merger history

The CANDELS/SHARDS multiwavelength catalog in GOODS-N : photometry, photometric redshifts, stellar masses, emission-line fluxes, and star formation rates

We present a WFC3 F160W (H-band) selected catalog in the CANDELS/GOODS-N field containing photometry from the ultraviolet (UV) to the far-infrared (IR), photometric redshifts, and stellar parameters derived from the analysis of the multiwavelength data. The catalog contains 35,445 sources over the 171 arcmin(2) of the CANDELS F160W mosaic. The 5 sigma detection limits (within an aperture of radius 0 ''.17) of the mosaic range between H = 27.8, 28.2, and 28.7 in the wide, intermediate, and deep regions, which span approximately 50%, 15%, and 35% of the total area. The multiwavelength photometry includes broadband data from the UV (U band from KPNO and LBC), optical (HST/ACS F435W, F606W, F775W, F814W, and F850LP), near-to-mid IR (HST/WFC3 F105W, F125W, F140W, and F160W; Subaru/MOIRCS Ks; CFHT/Megacam K; and Spitzer/IRAC 3.6, 4.5, 5.8, and 8.0 mu m), and far-IR (Spitzer/MIPS 24 mu m, HERSCHEL/PACS 100 and 160 mu m, SPIRE 250, 350 and 500 mu m) observations. In addition, the catalog also includes optical medium-band data (R similar to 50) in 25 consecutive bands, lambda = 500-950 nm, from the SHARDS survey and WFC3 IR spectroscopic observations with the G102 and G141 grisms (R similar to 210 and 130). The use of higher spectral resolution data to estimate photometric redshifts provides very high, and nearly uniform, precision from z = 0-2.5. The comparison to 1485 good-quality spectroscopic redshifts up to z similar to 3 yields Delta z/(1 + z(spec)) = 0.0032 and an outlier fraction of eta = 4.3%. In addition to the multiband photometry, we release value-added catalogs with emission-line fluxes, stellar masses, dust attenuations, UV- and IR-based star formation rates, and rest-frame colors

Recent Progress in the Use of Glucagon and Glucagon Receptor Antagonists in the Treatment of Diabetes Mellitus

Glucagon is an important pancreatic hormone, released into blood circulation by alpha cells of the islet of Langerhans. Glucagon induces gluconeogenesis and glycogenolysis in hepatocytes, leading to an increase in hepatic glucose production and subsequently hyperglycemia in susceptible individuals. Hyperglucagonemia is a constant feature in patients with T2DM. A number of bioactive agents that can block glucagon receptor have been identified. These glucagon receptor antagonists can reduce the hyperglycemia associated with exogenous glucagon administration in normal as well as diabetic subjects. Glucagon receptor antagonists include isoserine and beta-alanine derivatives, bicyclic 19-residue peptide BI-32169, Des-His1-[Glu9] glucagon amide and related compounds, 5-hydroxyalkyl-4-phenylpyridines, N-[3-cano-6- (1,1 dimethylpropyl)-4,5,6,7-tetrahydro-1-benzothien-2-yl]-2-ethylbutamide, Skyrin and NNC 250926. The absorption, dosage, catabolism, excretion and medicinal chemistry of these agents are the subject of this review. It emphasizes the role of glucagon in glucose homeostasis and how it could be applied as a novel tool for the management of diabetes mellitus by blocking its receptors with either monoclonal antibodies, peptide and non-peptide antagonists or gene knockout techniques

CANDELS multi-wavelength catalogs: source identification and photometry in the CANDELS COSMOS survey field

We present a multi-wavelength photometric catalog in the COSMOS field as part of the observations by the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey. The catalog is based on Hubble Space Telescope Wide Field Camera 3 (HST/WFC3) and Advanced Camera for Surveys observations of the COSMOS field (centered at R.A.: 10h00m28s, Decl.:+02h12m21s). The final catalog has 38671 sources with photometric data in 42 bands from UV to the infrared (~0.3-8 μm). This includes broadband photometry from HST, CFHT, Subaru, the Visible and Infrared Survey Telescope for Astronomy, and Spitzer Space Telescope in the visible, near-infrared, and infrared bands along with intermediate- and narrowband photometry from Subaru and medium-band data from Mayall NEWFIRM. Source detection was conducted in the WFC3 F160W band (at 1.6 μm) and photometry is generated using the Template FITting algorithm. We further present a catalog of the physical properties of sources as identified in the HST F160W band and measured from the multi-band photometry by fitting the observed spectral energy distributions of sources against templates

Current practices in lc-ms untargeted metabolomics: a scoping review on the use of pooled quality control samples

Untargeted metabolomics is an analytical approach with numerous applications serving as an effective metabolic phenotyping platform to characterize small molecules within a biological system. Data quality can be challenging to evaluate and demonstrate in metabolomics experiments. This has driven the use of pooled quality control (QC) samples for monitoring and, if necessary, correcting for analytical variance introduced during sample preparation and data acquisition stages. Described herein is a scoping literature review detailing the use of pooled QC samples in published untargeted liquid chromatography-mass spectrometry (LC-MS) based metabolomics studies. A literature query was performed, the list of papers was filtered, and suitable articles were randomly sampled. In total, 109 papers were each reviewed by at least five reviewers, answering predefined questions surrounding the use of pooled quality control samples. The results of the review indicate that use of pooled QC samples has been relatively widely adopted by the metabolomics community and that it is used at a similar frequency across biological taxa and sample types in both small- and large-scale studies. However, while many studies generated and analyzed pooled QC samples, relatively few reported the use of pooled QC samples to improve data quality. This demonstrates a clear opportunity for the field to more frequently utilize pooled QC samples for quality reporting, feature filtering, analytical drift correction, and metabolite annotation. Additionally, our survey approach enabled us to assess the ambiguity in the reporting of the methods used to describe the generation and use of pooled QC samples. This analysis indicates that many details of the QC framework are missing or unclear, limiting the reader's ability to determine which QC steps have been taken. Collectively, these results capture the current state of pooled QC sample usage and highlight existing strengths and deficiencies as they are applied in untargeted LC-MS metabolomics