Mcdowellholmgaard3854

Background Chronic use of proton-pump inhibitors (PPIs) is common in kidney transplant recipients (KTRs). However, concerns are emerging about the potential long-term complications of PPI therapy. We aimed to investigate whether PPI use is associated with excess mortality risk in KTRs. Methods and findings We investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 (ClinicalTrials.gov Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57% were male, and 56.6% used PPIs. During median follow-up of 8.2 (4.7-9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95% CI 1.38-2.52, P 20 mg omeprazole equivalents/day) compared with patients taking no PPIs (HR 2.14, 95% CI 1.48-3.09, P less then 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95% CI 1.23-2.39, P = 0.001). Tofacitinib supplier These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation. Conclusions We demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs. Trial registration ClinicalTrials.gov Identifier NCT02811835, NCT01331668.The most common methods for estimating the infiltration function are measurements through a double-ring infiltrometer (DRI) and empirical models. Infiltration data always exhibit different kinds of scatter, which affect the accuracy of the estimated infiltration function. This study presents a new methodology to calibrate the infiltration function. The suggested approach is based on combining the DRI method with the changes in the measured soil water content. Furrow irrigation experiments were conducted to estimate the infiltration function using different methods and to investigate the effect of data scatter on the reliability of the estimated infiltration function. Furrow elevations were observed, and for each irrigation event advance times, recession times, and inflow rates were observed. The infiltration depths were measured as a function of the change in the soil water content before and after irrigation event. Infiltration parameters were estimated using DRI treatment, empirical model (Kostiakov model), and suggested approach. Measured and simulated infiltration depths using the described methods were compared. The results show that the infiltration depths estimated using a DRI were lower than the observed infiltration depths, while the infiltration depths estimated using the empirical model were higher than the observed infiltration depths. The results indicate that the infiltration function estimated using the recommended approach was more accurate and reasonable than the infiltration function estimated using the DRI, and empirical (Kostiakov model) methods. In addition, the proposed approach can reduce the required measurements during the irrigation event, and can also reduce the potential scatter in the estimated infiltration function that results from soil variability and measurement errors.Metabolism underpins the pathogenic strategy of the causative agent of TB, Mycobacterium tuberculosis (Mtb), and therefore metabolic pathways have recently re-emerged as attractive drug targets. A powerful approach to study Mtb metabolism as a whole, rather than just individual enzymatic components, is to use a systems biology framework, such as a Genome-Scale Metabolic Network (GSMN) that allows the dynamic interactions of all the components of metabolism to be interrogated together. Several GSMNs networks have been constructed for Mtb and used to study the complex relationship between the Mtb genotype and its phenotype. However, the utility of this approach is hampered by the existence of multiple models, each with varying properties and performances. Here we systematically evaluate eight recently published metabolic models of Mtb-H37Rv to facilitate model choice. The best performing models, sMtb2018 and iEK1011, were refined and improved for use in future studies by the TB research community.Mechanisms underlying the manifestation of relatives' expressed emotion (EE) in the early stages of psychosis are still not properly understood. The present study aimed to examine whether relatives' psychological distress and subjective appraisals of the illness predicted EE dimensions over-and-above patients' poor clinical and functional status. Baseline patient-related variables and relatives attributes comprising criticism, emotional over-involvement (EOI), psychological distress, and illness attributions were assessed in 91 early psychosis patients and their respective relatives. Relatives were reassessed regarding EE dimensions at a 6-month follow-up. Relatives' psychological distress and illness attributions predicted criticism and EOI over-and-above patients' illness characteristics at both time points. Relatives' increased levels of anxiety, attributions of blame toward the patients, an emotional negative representation about the disorder, and decreased levels of self-blame attributions predicted EE-criticism at baseline. Relatives' anxiety and negative emotional representation of the disorder were the only significant predictors of EE-criticism at follow-up, whereas anxiety, attributions of control by the relative and an emotional negative representation about the disorder predicted EE-EOI both at baseline and follow-up assessments. Understanding the components that comprise and maintain EE attitudes should guide early psychosis caregivers in family interventions, enhancing proper management of psychological distress and reduction of negative appraisals about the illness. The prevention of high-EE attitudes over time in a sensitive period such as early psychosis might be critical in shaping the health of caregivers and the outcome of the affected relatives.