Primed (Germany)

Sharing diverse genomic and other biomedical datasets is critical to advance scientific discoveries and their equitable translation to improve human health. However, data sharing remains challenging in the context of legacy datasets, evolving policies, multi-institutional consortium science, and international stakeholders. The NIH-funded Polygenic Risk Methods in Diverse Populations (PRIMED) Consortium was established to improve the performance of polygenic risk estimates for a broad range of health and disease outcomes with global impacts. Improving polygenic risk score performance across genetically diverse populations requires access to large, diverse cohorts. We report on the design and implementation of data sharing policies and procedures developed in PRIMED to aggregate and analyze data from multiple, heterogeneous sources while adhering to existing data sharing policies for each integrated dataset. We describe two primary data sharing mechanisms: coordinated dbGaP applications and a Consortium Data Sharing Agreement, as well as provide alternatives when individual-level data cannot be shared within the Consortium (e.g., federated analyses). We also describe technical implementation of Consortium data sharing in the NHGRI Analysis Visualization and Informatics Lab-space (AnVIL) cloud platform, to share derived individual-level data, genomic summary results, and methods workflows with appropriate permissions. As a Consortium making secondary use of pre-existing data sources, we also discuss challenges and propose solutions for release of individual- and summary-level data products to the broader scientific community. We make recommendations for ongoing and future policymaking with the goal of informing future consortia and other research activities.

Introduction: Kidneys of marginal quality are increasingly being used to overcome the shortage of donor organs. However, accurate prediction of outcome is needed to optimize the use of these kidneys. We aimed to test the performance of a recently proposed score consisting of delayed graft function (DGF), renal function recovery (RFR), and glomerular filtration rate (GFR) <30 mL/min per 1.73 m2 90 days after transplantation for risk assessment of patient and graft survival. Material and Methods: A total of 221 adult brain death donors with marginal kidneys transplanted into 223 recipients within Eurotransplant were included in the analysis. Multivariable Cox proportional hazards models were constructed to assess death-censored and all-cause censored graft failure and recipient mortality at 1 and 3 years. Results: Recipients with DGF had a higher risk of death-censored graft loss (HR, 95% CIs: 3.058 [1.195–7.825]). Recipients with a GFR <30 mL/min/1.73 m2 at 90 days after transplantation had a higher risk of death censored and all-cause graft failure (HR, 95% CIs: 2.122 [1.129–3.990] and 2.122 [1.129–3.990]). None of the three components of the proposed score was associated with a higher risk of mortality. Conclusion: DGF and estimated GFR <30 mL/min/1.73 m2 but not RFR at 90 days predicted graft failure after transplantation of marginal kidneys. However, no combination of these factors was able to predict short-term patient and graft survival.

Inflammation and angiogenesis play an important role in the development of early diabetic kidney disease. We investigated the association of soluble Tumour Necrosis Factor Receptor 1 (sTNF-R1), sTNF-R2 and endostatin with new onset microalbuminuria in normoalbuminuric patients with diabetes mellitus type 2. We conducted a case control study to assess serum levels of sTNF-R1, sTNF-R2 and endostatin in 169 patients with new onset microalbuminuria and in 188 matched normoalbuminuric, diabetic controls. Baseline serum samples from participants of the ROADMAP (Randomized Olmesartan and Diabetes Microalbuminuria Prevention) and observational follow-up (ROADMAP-OFU) studies were used. Endostatin and sTNF-R1 but not sTNF-R2 were increased at baseline in patients with future microalbuminuria. In the multivariate analysis, each log2 increment in endostatin levels was associated with an increase of only 6% in the risk of development of microalbuminuria (adjusted HR (95% CI) 1.006 (1.001-1011). sTNF-R1 and sTNF-R2 levels were conversely associated with microalbuminuria, but the results did not reach statistical significance. The respective adjusted HRs (95% CI) were 1.305 (0.928-1.774) and 0.874 (0.711-1.074). sTNF-R1 and sTNF-R2 failed to predict the occurrence of microalbuminuria in normoalbuminuric patients with type 2 diabetes. Likewise, the utility of endostatin in predicting new onset proteinuria is limited.

In diesem Buch wird ausgewertet, wie deutsche Gerichte Partnerinnentötungen/Beziehungsfemizide sanktionieren (Tatbestand, Strafzumessung, Straflänge).

PurposeTo technically validate a novel pneumatically based system and method for modulation of intraocular pressure (IOP) and to test its application in the human eye. Special attention was paid to the applicability of the pneumatically driven balloon, which realizes the modulation of the IOP through its contact with the conjunctiva.MethodsA force sensor as key component of a customized measurement setup was used to check the applied pressure through the balloon. The IOP of 10 healthy subjects (4 female, 6 male, aged 28.8 ± 6.64 years) was modulated and increased linearly to at least 40 mmHg. At this point, the pressure inside the balloon was kept constant for 2 minutes, with IOP measurements taken every 40 seconds using a rebound tonometer.ResultsThe technical setup led to an IOP decrease of 0.71 mmHg within 2 minutes at an operating point of 40 mmHg. For all subjects, the IOP could be increased up to 42.8 ± 3.6 mmHg, whereby a mean pressure decrease of 2.4 mmHg/min was determined, which seems to be caused mainly by physiological processes.ConclusionsWith the new pneumatically based setup, a targeted modulation in terms of level and constancy of the IOP can be realized.Translational RelevanceAdditional and, compared with the technique according to Löw, a more precise and more constant methodology for the modulation of the IOP, can significantly simplify the determination of retinal vessel pressures for clinical application. It is suitable for practical questions concerning an enhanced retinal venous pressure.

Diabetic nephropathy (DN) is a devastating complication of diabetes mellitus (DM). Therefore, screening strategies in order to prevent its development and/or retard its progression are of paramount importance. We investigated if monocyte chemoattractant protein-1 (MCP-1) was associated with new onset microalbuminuria-the earliest sign of the albuminuric phenotype of DN- in patients with type 2 DM and normoalbuminuria. We measured MCP-1 in serum and urine samples from patients of the Randomized Olmesartan And Diabetes Microalbuminuria Prevention (ROADMAP) study and its Observational Follow-up (OFU) cohort. A case control design was used with inclusion of 172 patients who developed microalbuminuria (MA) and of 188 well matched controls who remained normoalbuminuric. The median duration of follow-up for the ROADMAP cohorts was 6.5 years, whereas the mean time until occurrence of MA was 53.2 months. In the multivariate analysis, serum and urine MCP-1 remained significant predictors of new onset MA. The risk for MA increased continuously with increasing serum and urine MCP-1 levels but reached statistical significance only in the highest quartiles. The risk associations were stronger with serum MCP-1. MCP-1 is a marker and possibly a mediator of early diabetic nephropathy. Further prospective studies are necessary to test whether diabetic patients with elevated MCP-1 levels would benefit from specific therapeutic interventions.

Media (nutrient agar) is a medium that is often used for bacteriological examinations and the price is relatively more expensive, Sorghum bicolor materials that are easy to get and cheap. Sorghum contains carbohydrates and protein which are suitable for manufacturing agar nutrients. This research was an experimental quantitative analysis laboratory. The research used Sorghum bicolor flour as carbohydrates and proteins in nutrient agar media. This study used variations in the mass of sorghum flour 2.50 grams, 3.75 grams, 5.00 grams, and 6.25 grams. The average number of bacterial colonies at mass variations was 2.50 grams, 3.75 grams, 5.00 grams, and 6.25 grams, namely 70.75 × 1013 CFU / mL, 60.75 × 1013 CFU / mL, 49, 25 × 1013 CFU / mL, and 42 × 1013 CFU / mL with significant differences in the value of p = 0.000 or <α = 0.05. 5.00 gram sorghum flour yields almost the same colony count as Nutrie Media for manufacturing as the gold standard. Conclusion 5 grams of sorghum flour can be used as an alternative media for nutrition and protein in Nutrient agar for Manufacturing. Keywords: sorghum bicolor l; moenchnutrient agar media; Escherichia coli