Drug-gene interactions of antihypertensive medications and risk of incident cardiovascular disease: a pharmacogenomics study from the CHARGE consortium

Background Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals. Methods Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases). Results Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0×10−8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction ≥ 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD

An analysis of partial efficiencies of energy utilisation of different macronutrients by barramundi (Lates calcarifer) shows that starch restricts protein utilisation in carnivorous fish

This study examined the effect of including different dietary proportions of starch, protein and lipid, in diets balanced for digestible energy, on the utilisation efficiencies of dietary energy by barramundi (Lates calcarifer). Each diet was fed at one of three ration levels (satiety, 80 % of initial satiety and 60 % of initial satiety) for a 42-d period. Fish performance measures (weight gain, feed intake and feed conversion ratio) were all affected by dietary energy source. The efficiency of energy utilisation was significantly reduced in fish fed the starch diet relative to the other diets, but there were no significant effects between the other macronutrients. This reduction in efficiency of utilisation was derived from a multifactorial change in both protein and lipid utilisation. The rate of protein utilisation deteriorated as the amount of starch included in the diet increased. Lipid utilisation was most dramatically affected by inclusion levels of lipid in the diet, with diets low in lipid producing component lipid utilisation rates well above 1·3, which indicates substantial lipid synthesis from other energy sources. However, the energetic cost of lipid gain was as low as 0·65 kJ per kJ of lipid deposited, indicating that barramundi very efficiently store energy in the form of lipid, particularly from dietary starch energy. This study defines how the utilisation efficiency of dietary digestible energy by barramundi is influenced by the macronutrient source providing that energy, and that the inclusion of starch causes problems with protein utilisation in this species

Marginal efficiencies of long chain-polyunsaturated fatty acid use by barramundi (Lates calcarifer) when fed diets with varying blends of fish oil and poultry fat

An experiment was conducted with barramundi (Lates calcarifer) juveniles to examine the marginal efficiency of utilisation of long chain-polyunsaturated fatty acids (LC-PUFA). A series of five diets with blends of fish (anchovy) oil and poultry fat (F100:P0, F60:P40, F30:P70, F15:P85, F0:P100) were fed to 208. ±. 4.1. g fish over a 12-week period. The replacement of fish oil with poultry fat had no impact on growth performance (average final weight of 548.3. ±. 10.2. g) or feed conversion (mean. =. 1.14. ±. 0.02). Analysis of the whole body composition showed that the fatty acid profile reflected that of the fed diet. However it was also shown that there was a disproportional retention of some fatty acids relative to others (notably LOA, 18:2n-6 and LNA, 18:3n-3). By examining the body mass independent retention of different fatty acids with differential levels of intake of each, the marginal efficiencies of the use of these nutrients by this species were able to be determined. The differential retention of fatty acids in the meat was also examined allowing the determination of oil blending strategies to optimise meat n-3 LC-PUFA levels. © 2015 Elsevier B.V

Existential Loneliness and end-of-life care: A Systematic Review

Contains fulltext : 88662.pdf (publisher's version ) (Closed access)Patients with a life-threatening illness can be confronted with various types of loneliness, one of which is existential loneliness (EL). Since the experience of EL is extremely disruptive, the issue of EL is relevant for the practice of end-of-life care. Still, the literature on EL has generated little discussion and empirical substantiation and has never been systematically reviewed. In order to systematically review the literature, we (1) identified the existential loneliness literature; (2) established an organising framework for the review; (3) conducted a conceptual analysis of existential loneliness; and (4) discussed its relevance for end-of-life care. We found that the EL concept is profoundly unclear. Distinguishing between three dimensions of EL-as a condition, as an experience, and as a process of inner growth-leads to some conceptual clarification. Analysis of these dimensions on the basis of their respective key notions-everpresent, feeling, defence; death, awareness, difficult communication; and inner growth, giving meaning, authenticity-further clarifies the concept. Although none of the key notions are unambiguous, they may function as a starting point for the development of care strategies on EL at the end of life.1 april 201

The Ursinus Weekly, May 3, 1965

Y retreat emphasizes creation of ideal college • Stage set for Fenwickian mouse • Ferguson, Dawson report $1,700 for Campus Chest • Psych Club elects officers • Bishop\u27s Players present An enemy of the people • Waiters\u27 banquet • Starvation: Paradox of plenty • Bali Ha\u27i theme for annual Spring Festival • Active electioneering marks class elections • Editorial: MSGA election; UC traditions and manners • Letters to the editor • One language for the world • Nine overseas students enrolled at Ursinus • Admissions dilemma • Injured thinclads bow at PMC; Win triangular meet at Hopkins • UC nine wins two: Beat F&M, Lebanon Valley • UC girls drop match to W.C. • Lacrosse team whips W. Chester • Greek gleanings • Advertising and PR seminarhttps://digitalcommons.ursinus.edu/weekly/1248/thumbnail.jp

Drug-gene interactions of antihypertensive medications and risk of incident cardiovascular disease: A pharmacogenomics study from the CHARGE consortium

Background Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals. Methods Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk ofmajor cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regressionmodels to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases). Results Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0×10-8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genom

Tour the United VCU, The Premier Urban Research University

This project will capitalize on the existing Open House weekends by offering a 60 minute tour of the MCV Campus. The tour will expose prospective students to VCU as a whole, highlighting the diverse range of studies and to present VCU as one university. The bus ride and walking tour will showcase the connection and relevance of both campuses, allowing prospective students with a myriad of interests to see all that VCU has to offer

Pennsylvania Folklife Vol. 43, No. 2

• The America\u27s Industrial Heritage Project: A Model for Cultural Tourism • The Harmonists are Waiting for You • The Quest for Authenticity in Tourism and Folklife Studies • Tourism and the Old Order Amish • The Log Cabin: Notes on its Structure and Dissemination • On the Making of Die Union Choral Harmonie (1833): Evidence from Henry C. Eyer\u27s Working Papers • In Memoriam: Paul R. Wieand, a True Artisthttps://digitalcommons.ursinus.edu/pafolklifemag/1139/thumbnail.jp

A compendium of raw material digestibilities for barramundi, Lates calcarifer

A series of experiments were conducted to examine the nutrient and energy digestibility of a suite of diets and specific test raw materials when fed to juvenile (179 to 439g) barramundi, Lates calcarifer. Each of the diets was prepared using a twin-screw extruder to mimic modern aquafeed manufacturing processes. Each of the diets was fed to juvenile barramundi for a minimum of a week to allow acclimation to the diet before the faeces were collected using stripping methods. A broad range of digestible nutrient and energy values among the different raw materials were observed, with protein digestibilities ranging from 36% to 106% and energy digestibilities ranging from 36% to 93%. This range in nutritional values of the different raw materials provides substantial utility in allowing the formulation of diets on a digestible nutrient and energy basis across the Asia Pacific region. These results also provide critical data to help underpin the replacement of both fishmeal and fish oil in barramundi diets

The Ursinus Weekly, April 12, 1965

Farewell and welcome: 12th annual senior banquet • Women elect WSGA officers • Sprecher, Rodimer, Tucker and Katz named editors: Production staff also announced • YW-YMCA freshman camp plans now in progress • Summer reading program supplemented by film • Spring fashions grace Bomberger; Proceeds support foster child • Soc. classes hear Lloyd • Spirit Committee announces bake sale • Save money, read this note • Editorial: Our policy • Kennedy memorial day • YM-YWCA volunteer service programs • Red Chinese use truth against P.O.W.s • $400,000 a year? • Lantern and Giefan move toward merger • Baseball team drops opener • Cindermen extend streak: Trackmen rip Muhlenberg & H\u27ford • West Chester downed: Snellbelles end season with hard fought victory • Mermaids end season • Tennis team wins • Beta Sig new intramural champs • Letters to the editorhttps://digitalcommons.ursinus.edu/weekly/1245/thumbnail.jp