“They can do whatever they want”: Meanings of receiving psychiatric care based on a common staff approach

This study deepens our understanding of how patients, when cared for in a psychiatric ward, experience situations that involve being handled according to a common staff approach. Interviews with nine former psychiatric in-patients were analyzed using a phenomenological–hermeneutic method to illuminate the lived experience of receiving care based on a common staff approach. The results revealed several meanings: discovering that you are as subjected to a common staff approach, becoming aware that no one cares, becoming aware that your freedom is restricted, being afflicted, becoming aware that a common staff approach is not applied by all staff, and feeling safe because someone else is responsible. The comprehensive understanding was that the patient's understanding of being cared for according to a common staff approach was to be seen and treated in accordance with others' beliefs and valuations, not in line with the patients' own self-image, while experiencing feelings of affliction

Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease.

BACKGROUND: The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS: Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS: We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P=4.2×10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P=4.0×10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P=0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P=0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P=2.0×10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P=2.5×10(-7)). CONCLUSIONS: We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease. (Funded by the National Institutes of Health and others.).Supported by a career development award from the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH) (K08HL114642 to Dr. Stitziel) and by the Foundation for Barnes–Jewish Hospital. Dr. Peloso is supported by the National Heart, Lung, and Blood Institute of the NIH (award number K01HL125751). Dr. Kathiresan is supported by a Research Scholar award from the Massachusetts General Hospital, the Donovan Family Foundation, grants from the NIH (R01HL107816 and R01HL127564), a grant from Fondation Leducq, and an investigator-initiated grant from Merck. Dr. Merlini was supported by a grant from the Italian Ministry of Health (RFPS-2007-3-644382). Drs. Ardissino and Marziliano were supported by Regione Emilia Romagna Area 1 Grants. Drs. Farrall and Watkins acknowledge the support of the Wellcome Trust core award (090532/Z/09/Z), the British Heart Foundation (BHF) Centre of Research Excellence. Dr. Schick is supported in part by a grant from the National Cancer Institute (R25CA094880). Dr. Goel acknowledges EU FP7 & Wellcome Trust Institutional strategic support fund. Dr. Deloukas’s work forms part of the research themes contributing to the translational research portfolio of Barts Cardiovascular Biomedical Research Unit, which is supported and funded by the National Institute for Health Research (NIHR). Drs. Webb and Samani are funded by the British Heart Foundation, and Dr. Samani is an NIHR Senior Investigator. Dr. Masca was supported by the NIHR Leicester Cardiovascular Biomedical Research Unit (BRU), and this work forms part of the portfolio of research supported by the BRU. Dr. Won was supported by a postdoctoral award from the American Heart Association (15POST23280019). Dr. McCarthy is a Wellcome Trust Senior Investigator (098381) and an NIHR Senior Investigator. Dr. Danesh is a British Heart Foundation Professor, European Research Council Senior Investigator, and NIHR Senior Investigator. Drs. Erdmann, Webb, Samani, and Schunkert are supported by the FP7 European Union project CVgenes@ target (261123) and the Fondation Leducq (CADgenomics, 12CVD02). Drs. Erdmann and Schunkert are also supported by the German Federal Ministry of Education and Research e:Med program (e:AtheroSysMed and sysINFLAME), and Deutsche Forschungsgemeinschaft cluster of excellence “Inflammation at Interfaces” and SFB 1123. Dr. Kessler received a DZHK Rotation Grant. The analysis was funded, in part, by a Programme Grant from the BHF (RG/14/5/30893 to Dr. Deloukas). Additional funding is listed in the Supplementary Appendix.This is the author accepted manuscript. The final version is available from the Massachusetts Medical Society via http://dx.doi.org/10.1056/NEJMoa150765

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Modeling nitrous oxide emissions from agricultural soil incubation experiments using CoupModel

Efforts to develop effective climate mitigation strategies for agriculture require methods to estimate nitrous oxide (N2O) emissions from soil. Process-based biogeochemical models have been often used for field- and large-scale estimates, while the sensitivity and uncertainty of model applications to incubation experiments are less investigated. In this study, a process-oriented model (CoupModel) was used to simulate N2O and CO2 fluxes and soil mineral nitrogen (N) contents in a short-term (43 d) factorial incubation experiment (16 treatments). A global sensitivity analysis (GSA) approach, "Morris screening", was applied to quantify parameter sensitivity. The GSA suggested that a higher number of sensitive parameters was associated with N2O flux estimates and that inter-treatment variations in parameter sensitivities were distinguished by soil moisture levels or NO3- content and residue types. Important parameters regarding N2O flux estimates were linked to the decomposability of soil organic matter (e.g., organic C pool sizes) and the denitrification process (e.g., Michaelis constant and denitrifier respiratory rates). After calibration, the model better captured temporal variations and magnitude of gas fluxes and mineral N in unamended soils than in residue-amended soils. Low-magnitude daily and cumulative N2O fluxes were well simulated with mean errors (MEs) close to zero, but the model tended to underestimate N2O fluxes, as observed daily values increased by over 0.1 g N m-2 d-1, in which the major mismatch was due to limited success of the model to describe the high emissions during the first few days after crop residue addition. A larger uncertainty was also seen in the magnitude of pulse emissions by the posterior simulations. We also evaluated ancillary variables regarding N cycling, which indicated that more frequent measurements and additional types of observed data such as soil oxygen content and the microbial sources of emitted N2O are required to further evaluate model performance and biases. The major challenges for calibration were associated with high sensitivities of denitrification parameters to initial soil abiotic conditions and the instantaneous residue amendment. Model structure uncertainties and improved modeling practices in the context of incubation experiments were discussed

Superhard NbB2 −x thin films deposited by dc magnetron sputtering

We have deposited weakly textured substoichiometric NbB2-x thin films by magnetron sputtering from an NbB2 target. The films exhibit superhardness (42 +/- 4 GPa), previously only observed in overstoichiometric TiB2 thin films, and explained by a self-organized nanostructuring, where thin TiB2 columnar grains hinder nucleation and slip of dislocations and a B-rich tissue phase between the grains prevent grain-boundary sliding. The wide homogeneity range for the NbB2 phase allows a similar ultra-thin B-rich tissue phase to form between thin (5-10 nm) columnar NbB2-x grains also for films with a B/Nb atomic ratio of 1.8, as revealed here by analytical aberration-corrected scanning transmission electron microscopy. Furthermore, a coefficient of friction of 0.16 is measured for an NbB2-x film sliding against stainless steel with a wear rate of 5 x 10(-7) mm(3)/Nm. X-ray photoelectron spectroscopy results suggest that the low friction is due to the formation of a lubricating boric acid film.Funding Agencies|Vinnova (Swedish Governmental Agency for Innovation Systems) through the VINN Excellence Centre FunMat; Swedish Foundation of Strategic Research through the Synergy Grant FUNCASE; Knut and Alice Wallenberg Foundation</p