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Search Results: 1 - 10 of 197222 matches for " Peter E. Weeke "
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The prognostic importance of a history of hypertension in patients with symptomatic heart failure is substantially worsened by a short mitral inflow deceleration time
Charlotte Andersson, Gunnar H Gislason, Peter Weeke, Jesper Kjaergaard, Christian Hassager, Dilek Akkan, Jacob E M?ller, Lars K?ber, Christian Torp-Pedersen
BMC Cardiovascular Disorders , 2012, DOI: 10.1186/1471-2261-12-30
Abstract: 3078 consecutively hospitalized heart failure patients (NYHA classes II-IV) were screened for the EchoCardiography and Heart Outcome Study (ECHOS). The left ventricular ejection fraction (LVEF) was estimated by 2 dimensional transthoracic echocardiography in all patients and a subgroup of 878 patients had additional data on pulsed wave Doppler assessment of transmitral flow available. A restrictive filling (RF) was defined as a mitral inflow deceleration time ≤140?ms. Patients were followed for a median of 6.8 (Inter Quartile Range 6.6-7.0) years and multivariable Cox regression models were used to assess the risk of all-cause mortality associated with hypertension.The study population had a mean age of 73?±?11?years. 39% were female, 27% had a history of hypertension and 48% had a RF. Over the study period, 64% of the population died. Hypertension was not associated with increased risk of mortality, hazard ratio (HR) 0.95 (0.85-1.05). LVEF did not modify this relationship (p for interaction?=?0.7), but RF pattern substantially influenced the outcomes associated with hypertension (p for interaction?<?0.001); HR 0.75 (0.57-0.99) and 1.41 (1.08-1.84) in patients without and with RF, respectively.In patients with symptomatic heart failure, a history of hypertension is associated with a substantially increased relative risk of mortality among patients with a restrictive transmitral filling pattern.
Integrating EMR-Linked and In Vivo Functional Genetic Data to Identify New Genotype-Phenotype Associations
Jonathan D. Mosley, Sara L. Van Driest, Peter E. Weeke, Jessica T. Delaney, Quinn S. Wells, Lisa Bastarache, Dan M. Roden, Josh C. Denny
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0100322
Abstract: The coupling of electronic medical records (EMR) with genetic data has created the potential for implementing reverse genetic approaches in humans, whereby the function of a gene is inferred from the shared pattern of morbidity among homozygotes of a genetic variant. We explored the feasibility of this approach to identify phenotypes associated with low frequency variants using Vanderbilt's EMR-based BioVU resource. We analyzed 1,658 low frequency non-synonymous SNPs (nsSNPs) with a minor allele frequency (MAF)<10% collected on 8,546 subjects. For each nsSNP, we identified diagnoses shared by at least 2 minor allele homozygotes and with an association p<0.05. The diagnoses were reviewed by a clinician to ascertain whether they may share a common mechanistic basis. While a number of biologically compelling clinical patterns of association were observed, the frequency of these associations was identical to that observed using genotype-permuted data sets, indicating that the associations were likely due to chance. To refine our analysis associations, we then restricted the analysis to 711 nsSNPs in genes with phenotypes in the On-line Mendelian Inheritance in Man (OMIM) or knock-out mouse phenotype databases. An initial comparison of the EMR diagnoses to the known in vivo functions of the gene identified 25 candidate nsSNPs, 19 of which had significant genotype-phenotype associations when tested using matched controls. Twleve of the 19 nsSNPs associations were confirmed by a detailed record review. Four of 12 nsSNP-phenotype associations were successfully replicated in an independent data set: thrombosis (F5,rs6031), seizures/convulsions (GPR98,rs13157270), macular degeneration (CNGB3,rs3735972), and GI bleeding (HGFAC,rs16844401). These analyses demonstrate the feasibility and challenges of using reverse genetics approaches to identify novel gene-phenotype associations in human subjects using low frequency variants. As increasing amounts of rare variant data are generated from modern genotyping and sequence platforms, model organism data may be an important tool to enable discovery.
Duration of clopidogrel treatment and risk of mortality and recurrent myocardial infarction among 11 680 patients with myocardial infarction treated with percutaneous coronary intervention: a cohort study
Rikke S?rensen, Steen Z Abildstrom, Peter Weeke, Emil L Fosb?l, Fredrik Folke, Morten L Hansen, Peter R Hansen, Jan K Madsen, Ulrik Abildgaard, Lars K?ber, Henrik E Poulsen, Christian Torp-Pedersen, Gunnar H Gislason
BMC Cardiovascular Disorders , 2010, DOI: 10.1186/1471-2261-10-6
Abstract: Using nationwide registers of hospitalizations and drug dispensing from pharmacies we identified 11 680 patients admitted with MI, treated with PCI and clopidogrel. Clopidogrel treatment was categorized in a 6-months and a 12-months regimen. Rates of death, recurrent MI or a combination of both were analyzed by the Kaplan Meier method and Cox proportional hazards models. Bleedings were compared between treatment regimens.The Kaplan Meier analysis indicated no benefit of the 12-months regimen compared with the 6-months in all endpoints. The Cox proportional hazards analysis confirmed these findings with hazard ratios for the 12-months regimen (the 6-months regimen used as reference) for the composite endpoint of 1.01 (confidence intervals 0.81-1.26) and 1.24 (confidence intervals 0.95-1.62) for Day 0-179 and Day 180-540 after discharge. Bleedings occurred in 3.5% and 4.1% of the patients in the 6-months and 12-months regimen (p = 0.06).We found comparable rates of death and recurrent MI in patients treated with 6- and 12-months' clopidogrel. The potential benefit of prolonged clopidogrel treatment in a real-life setting remains uncertain.Clopidogrel reduces coronary ischemic events in patients with acute coronary syndrome[1] and after percutaneous coronary intervention (PCI) where the beneficial effect is evident within the first 24 hours of treatment initiation[2-4]. In the past 5 years there has been a clear tendency to recommend increased duration of clopidogrel treatment. Current guidelines recommend 12 months of treatment for all patients after non-ST-elevation myocardial infarction, ST-elevation myocardial infarction and after treatment with PCI, in the absence of a high risk of bleeding[5-7]. The optimal duration of clopidogrel treatment is a major clinical issue, as clopidogrel, in addition to the desired anti-thrombotic effect, poses a considerable risk of bleeding. Premature cessation has been associated with increased risk of thrombotic events, including s
Diabetes is associated with impaired myocardial performance in patients without significant coronary artery disease
Charlotte Andersson, Gunnar H Gislason, Peter Weeke, S?ren Hoffmann, Peter R Hansen, Christian Torp-Pedersen, Peter S?gaard
Cardiovascular Diabetology , 2010, DOI: 10.1186/1475-2840-9-3
Abstract: Patients with a left ventricular (LV) ejection fraction (EF) > 35% and without significant CAD, prior myocardial infarction, cardiac pacemaker, atrial fibrillation, or significant valve disease were identified from a tertiary invasive center register. DM patients were matched with controls on age, gender and presence of hypertension.In total 31 patients with diabetes and 31 controls were included. Mean age was 58 ± 12 years, mean LVEF was 51 ± 7%, and 48% were women. No significant differences were found in LVEF, left atrial end systolic volume, or left ventricular dimensions. The global longitudinal strain was significantly reduced in patients with DM (15.9 ± 2.9 vs. 17.7 ± 2.9, p = 0.03), as were peak longitudinal systolic (S') and early diastolic (E') velocities (5.7 ± 1.1 vs. 6.4 ± 1.1 cm/s, p = 0.02 and 6.1 ± 1.7 vs. 7.7 ± 2.0 cm/s, p = 0.002). In multivariable regression analyses, DM remained significantly associated with impairments of S' and E', respectively.In patients without significant CAD, DM is associated with an impaired systolic longitudinal LV function and global diastolic dysfunction. These abnormalities are likely to be markers of adverse prognosis.Patients with diabetes mellitus (DM) have an increased risk of developing heart failure compared to patients without DM[1,2]. Whether this increased risk is solely based on coronary artery disease (CAD) and hypertension, or whether some of the risk might be explained by a direct influence of DM on cardiac function (diabetic cardiomyopathy) is incompletely understood.Diabetic cardiomyopathy has been defined as the presence of myocardial abnormalities in the absence of coronary artery disease, hypertension or other significant etiology[3]. Several experimental studies have identified changes consistent with diabetic cardiomyopathy, including microangiopathy, metabolic disturbances and myocardial fibrosis[4]. The evidence of a clinical impact of diabetic cardiomyopathy on myocardial function has increased
Mechanistic Phenotypes: An Aggregative Phenotyping Strategy to Identify Disease Mechanisms Using GWAS Data
Jonathan D. Mosley, Sara L. Van Driest, Emma K. Larkin, Peter E. Weeke, John S. Witte, Quinn S. Wells, Jason H. Karnes, Yan Guo, Lisa Bastarache, Lana M. Olson, Catherine A. McCarty, Jennifer A. Pacheco, Gail P. Jarvik, David S. Carrell, Eric B. Larson, David R. Crosslin, Iftikhar J. Kullo, Gerard Tromp, Helena Kuivaniemi, David J. Carey, Marylyn D. Ritchie, Josh C. Denny, Dan M. Roden
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0081503
Abstract: A single mutation can alter cellular and global homeostatic mechanisms and give rise to multiple clinical diseases. We hypothesized that these disease mechanisms could be identified using low minor allele frequency (MAF<0.1) non-synonymous SNPs (nsSNPs) associated with “mechanistic phenotypes”, comprised of collections of related diagnoses. We studied two mechanistic phenotypes: (1) thrombosis, evaluated in a population of 1,655 African Americans; and (2) four groupings of cancer diagnoses, evaluated in 3,009 white European Americans. We tested associations between nsSNPs represented on GWAS platforms and mechanistic phenotypes ascertained from electronic medical records (EMRs), and sought enrichment in functional ontologies across the top-ranked associations. We used a two-step analytic approach whereby nsSNPs were first sorted by the strength of their association with a phenotype. We tested associations using two reverse genetic models and standard additive and recessive models. In the second step, we employed a hypothesis-free ontological enrichment analysis using the sorted nsSNPs to identify functional mechanisms underlying the diagnoses comprising the mechanistic phenotypes. The thrombosis phenotype was solely associated with ontologies related to blood coagulation (Fisher's p = 0.0001, FDR p = 0.03), driven by the F5, P2RY12 and F2RL2 genes. For the cancer phenotypes, the reverse genetics models were enriched in DNA repair functions (p = 2×10?5, FDR p = 0.03) (POLG/FANCI, SLX4/FANCP, XRCC1, BRCA1, FANCA, CHD1L) while the additive model showed enrichment related to chromatid segregation (p = 4×10?6, FDR p = 0.005) (KIF25, PINX1). We were able to replicate nsSNP associations for POLG/FANCI, BRCA1, FANCA and CHD1L in independent data sets. Mechanism-oriented phenotyping using collections of EMR-derived diagnoses can elucidate fundamental disease mechanisms.
The weight lowering effect of sibutramine and its impact on serum lipids in cardiovascular high risk patients with and without type 2 diabetes mellitus - an analysis from the SCOUT lead-in period
Peter Weeke, Charlotte Andersson, Emil L Fosb?l, Bente Brendorp, Lars K?ber, Arya M Sharma, Nick Finer, Philip T James, Ian D Caterson, Richard A Rode, Christian Torp-Pedersen
BMC Endocrine Disorders , 2010, DOI: 10.1186/1472-6823-10-3
Abstract: The Sibutramine Cardiovascular OUTcomes (SCOUT) trial included obese and overweight patients at increased risk of cardiovascular events. All patients received guidance on diet and exercise plus once-daily 10 mg sibutramine during the 6-week, single blind lead-in period. Multivariable regression models were used to investigate factors associated with changes in lipid levels during the first four weeks of treatment.A total of 10 742 patients received at least one dose of sibutramine during the 6-week lead-in period of SCOUT. After four weeks, patients experienced mean reductions in low density lipoprotein (LDL-C) 0.19 mmol/L, high density lipoprotein (HDL-C) 0.019 mmol/L, very low density lipoprotein (VLDL-C) 0.08 mmol/L, total cholesterol (TC) 0.31 mmol/L and triglycerides 0.24 mmol/L (p < 0.0001 for each). Four week changes in LDL-C, HDL-C and total cholesterol for patients without vs. with T2D were: LDL-C:-0.25 mmol/L vs. -0.18 mmol/L, P = 0.0004; HDL-C: -0.03 mmol/L vs. -0.02 mmol/L, P = 0.0014; total cholesterol: -0.37 mmol/l vs. -0.29 mmol/l, P = 0.0009. Multivariable regression analysis showed that similar decreases in body mass index (BMI) affected lipid changes differently according to diabetes status. A 1 kg/m2 decrease in BMI in patients with T2D was associated with -0.09 mmol/L in LDL-C (P < 0.0001) and -0.01 mmol/L in HDL-C (P = 0.0001) but larger changes of -0.16 mmol/L LDL-C and -0.03 mmol/L in HDL-C (P < 0.0001 for both) in patients without T2D.Short term weight management with sibutramine therapy in obese or overweight high-risk patients induced significant mean reductions for all lipids. Those without T2D benefited most. Patients with hyperlipidaemia and the less obese patients also had greater falls in LDL-C and TC during weight loss. The trial is registered at ClinicalTrial.gov number: NCT00234832.Obesity, hyperlipidaemia and type-2 diabetes mellitus (T2D) are well known risk factors for developing cardiovascular disease (CVD)[1,2]. It has been sho
Differential changes in serum uric acid concentrations in sibutramine promoted weight loss in diabetes: results from four weeks of the lead-in period of the SCOUT trial
Charlotte Andersson, Peter Weeke, Bente Brendorp, Lars K?ber, Emil L Fosb?l, Arya M Sharma, Nick Finer, Ian D Caterson, Richard A Rode, Philip T James, Christian Torp-Pedersen
Nutrition & Metabolism , 2009, DOI: 10.1186/1743-7075-6-42
Abstract: Data from a four week single-blind lead-in period of the Sibutramine Cardiovascular OUTcomes (SCOUT) study were analyzed. 2584 patients (24%) had diabetes mellitus (DM) only, 1748 (16%) had cardiovascular disease (CVD) only and 6397 (60%) had both DM + CVD. Uric acid concentrations (mean ± standard deviation) at screening were significantly higher among patients with CVD compared to patients without CVD (p < 0.0001): 369 ± 86 μmol/L, 374 ± 98 μmol/L and 342 ± 87 μmol/L in CVD only, CVD+DM and DM only groups, respectively. During treatment uric acid decreased significantly more in patients without DM (p < 0.0001): -15.0 μmol/L (95% confidence interval -17.7;-12.4), -4.6 μmol/L (-6.2;-3.0), and -6.6 μmol/L (-8.7;-4.5) in CVD only, CVD+DM, and DM only groups, respectively. In patients who failed to lose weight, sibutramine induced lower uric acid levels, but greater weight loss and diabetes were associated with smaller falls in blood uric acid levels; decreasing fasting and urinary glucose concentrations in diabetes were associated with increases in uric acid levels.A four week daily intake of sibutramine and life style changes was associated with significant reductions in mean uric acid levels. Changes in renal glucose load in diabetes seem to counteract a potential uricosuric effect of sibutramine.The trial is registered at ClinicalTrial.gov number: NCT00234832.Large epidemiological studies of populations at increased risk of cardiovascular events (including those with diabetes, hypertension and a history of cardiovascular disease) show hyperuricaemia to powerfully predict cardiovascular adverse events and mortality[1-3], even within the high normal range of uric acid concentrations[4]. Hyperuricaemia may, however, simply reflect established cardiovascular risk factors, such as hypertension and renal impairment and not act causally[5].Elevated serum uric acid levels, obesity, insulin resistance and type 2 diabetes mellitus frequently coexist[6,7] and weight loss with
Threat Status of Commercially Exploited Trees in the Nigerian Rainforest  [PDF]
Francis E. Bisong, Peter Buckley
Open Journal of Forestry (OJF) , 2014, DOI: 10.4236/ojf.2014.45058
Abstract: Unregulated commercial-scale exploitation of trees is an indication of the extent of threat to various tree species. The study examined the threat status of commercially exploited trees in the forest estates of South eastern Nigeria. Specifically, it identified tree species under threat, and categorized them into threat classes, as well as determined the rate at which exploited trees were slipping into extinction. The study utilized the IUCN’s threat categorization criteria, in determining the threat status of commercially exploited trees. This study combined both secondary and primary data sources generated through Forest Inventory records, Tree Felled Analysis records and Participatory Survey. Data such as population size and density of species, level of exploitation and threat sensitive social and ecological parameters were obtained and applied against the IUCN criteria. Twenty-eight (28) trees species representing Thirty-two percent (32%) of eighty-six (86) commercially exploited trees were identified as threatened, ranging from the Vulnerable to the Critically Endangered categories. The theory of small and declining population paradigms were found to be of relevance in explaining the processes. Nine tree species such as Triplochiton spp., Baillonella toxisperma, Pogaoleosa, Anopyxis spp. among others were considered to require urgent conservation attention. Recommendations are proposed to halt the process of decline in the biodiversity of exploited trees.
Flow Simulation to Determine the Effects of Shrouds on the Performance of Wind Turbines  [PDF]
Peter E. Jenkins, Abdalfadel Younis
Journal of Power and Energy Engineering (JPEE) , 2016, DOI: 10.4236/jpee.2016.48008
Abstract: This paper describes a flow simulation model used to determine the effects of a shroud on the performance of a wind turbine. Also, it focuses on comparing the standard type of wind turbines— upwind turbine with three blades fixed on a horizontal axis—with a new type that is called a shrouded wind turbine. In addition, the two types of turbines are compared in terms of velocities profiles, pressure distribution and power output when applying four different velocities of winds: 10, 20, 30, 40 mph. Numerical values and graphs are highlighted in order to show the main differences between the shrouded turbine and the conventional one. Finally, a conclusion and some recommendations are provided to summarize the scope of this research and give a better prediction for a future optimal design of the shrouded turbines.
Simulink/MATLAB Model for Assessing the Use of a Centrifugal Pump as a Hydraulic Turbine  [PDF]
Peter E. Jenkins, Artem Kuryachy
World Journal of Mechanics (WJM) , 2018, DOI: 10.4236/wjm.2018.87021
Abstract: A centrifugal pump used as a hydraulic turbine in producing power for a microhydropower system is multifaceted. Centrifugal pumps are far more ubiquitous than turbines in the turbomachinery market, therefore being more readily available to the consumer. Additionally, they are cheaper. Hydraulic turbines undergo rigorous CFD simulation design and testing to establish their blade geometries and ranges of operation. This results in a refined but very expensive final product. Centrifugal pumps are thus presented as a logical alternative seeing that they can physically perform the same task as a hydropower turbine albeit at a reduced efficiency. This paper presents the results of an analysis and simulation to assess the use of a centrifugal pump as a hydraulic turbine.
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