Canine ovariohysterectomy: a survey of surgeon concerns and surgical complications encountered by newly graduated veterinarians

The objective of this study was to document newly qualified veterinarians’ concerns and surgical complications encountered during canine ovariohysterectomy (cOVH) during the first year of general practice. A questionnaire investigating concerns about cOVH procedures was sent to all final-year veterinary students (group 1) enrolled at five UK universities. Participants were later asked to complete a similar questionnaire 6 months (group 2) and 12 months (group 3) after graduation, which involved grading their concern about different aspects of the cOVH procedure and reporting surgical complications encountered after completing three cOVHs. Responses were compared between different time points. There were 196 respondents in group 1, 55 in group 2, and 36 in group 3. Between groups 1 and 2, there was a statistically significant reduction in the respondents’ levels of concern in every aspect of cOVH (p < .05). Between groups 2 and 3, there was no statistically significant change in respondents’ levels of concern in any aspect of cOVH (pb.21). There was a significant reduction in the number of complications encountered by veterinarians in group 3 (39/102, 38.2%) compared to those in group 2 (117/206, 56.8%) (p ¼ .002). Employers should anticipate high levels of concern regarding all aspects of cOVHs in new graduates, and supervision during the first 6 months may be particularly useful

Identification of a Novel Class of Farnesylation Targets by Structure-Based Modeling of Binding Specificity

Farnesylation is an important post-translational modification catalyzed by farnesyltransferase (FTase). Until recently it was believed that a C-terminal CaaX motif is required for farnesylation, but recent experiments have revealed larger substrate diversity. In this study, we propose a general structural modeling scheme to account for peptide binding specificity and recapitulate the experimentally derived selectivity profile of FTase in vitro. In addition to highly accurate recovery of known FTase targets, we also identify a range of novel potential targets in the human genome, including a new substrate class with an acidic C-terminal residue (CxxD/E). In vitro experiments verified farnesylation of 26/29 tested peptides, including both novel human targets, as well as peptides predicted to tightly bind FTase. This study extends the putative range of biological farnesylation substrates. Moreover, it suggests that the ability of a peptide to bind FTase is a main determinant for the farnesylation reaction. Finally, simple adaptation of our approach can contribute to more accurate and complete elucidation of peptide-mediated interactions and modifications in the cell

Standards and Practices for Forecasting

One hundred and thirty-nine principles are used to summarize knowledge about forecasting. They cover formulating a problem, obtaining information about it, selecting and applying methods, evaluating methods, and using forecasts. Each principle is described along with its purpose, the conditions under which it is relevant, and the strength and sources of evidence. A checklist of principles is provided to assist in auditing the forecasting process. An audit can help one to find ways to improve the forecasting process and to avoid legal liability for poor forecasting

Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci

To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 x 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p <2.4 x 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 x 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 x 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 x 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

In-situ Measurements of Tropospheric Hydroxyl Radicals by Folded Long-Path Laser Absorption During the Field Campaign POPCORN

Absolutely calibrated in-situ measurements of tropospheric hydroxyl radicals, formaldehyde, sulfur dioxide, and naphthalene (C10H8) were performed by long-path laser absorption spectroscopy during the field campaign POPCORN. The absorption light path was folded into an open optical multiple reflection cell with a mirror separation of 38.5 m. Using a light path length of 1848 m and an integration time of 200 s, the average 1 sigma-detection limits of OH, HCHO, SO2 and C10H8 during POPCORN were 8.710(5) cm(-3): 8.3.10(9) cm(-3), 2.4.10(9) cm(-3), 1.5.10(8) cm(-3), respectively. In total, 392 identifications of OH in air spectra were made in a rural environment between August 5 and August 23, 1994. We present and discuss OH absorption spectra and diurnal OH concentration profiles of three days which are representative for measurements under different pollution conditions during POPCORN. The observed maximum and median OH radical concentrations are 1.3.10(7) OH/cm(3) and 4.0.10(6) OH/cm(3), respectively. The measured diurnal variation of the OH concentration shows a good correlation with the primary formation reaction of OH radicals which is the photolysis of ambient ozone. Deviations from this correlation in the morning and evening hours, when the OH concentration is higher than expected from the ozone photolysis, demonstrate the importance of other photochemical HOx production pathways during POPCORN