Frequency relations for storm rainfall in Illinois

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Rainfall relations on small areas in Illinois

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Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10−8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis

Risk factors for atrial fibrillation in a multicenter United States clinical cohort of people with HIV infection

To assess atrial fibrillation risk factors in people with HIV, we identified incident atrial fibrillation in a large clinical cohort of people receiving care. Compared with 970 controls without atrial fibrillation, the 97 with adjudicated incident atrial fibrillation were older, less likely Hispanic, and had more coronary disease, heart failure, and chronic obstructive pulmonary disease. In multivariable analysis, nonuse of antiretroviral therapy and prescription of antiretroviral regimens with multiple core agents were associated with increased atrial fibrillation risk

Genome-wide meta-analysis of variant-by-diuretic interactions as modulators of lipid traits in persons of European and African ancestry

Hypertension (HTN) is a significant risk factor for cardiovascular morbidity and mortality. Metabolic abnormalities, including adverse cholesterol and triglycerides (TG) profiles, are frequent comorbid findings with HTN and contribute to cardiovascular disease. Diuretics, which are used to treat HTN and heart failure, have been associated with worsening of fasting lipid concentrations. Genome-wide meta-analyses with 39,710 European-ancestry (EA) individuals and 9925 African-ancestry (AA) individuals were performed to identify genetic variants that modify the effect of loop or thiazide diuretic use on blood lipid concentrations. Both longitudinal and cross sectional data were used to compute cohort-specific interaction results, which were then combined through meta-analysis in each ancestry. These ancestry-specific results were further combined through trans-ancestry meta-analysis. Analysis of EA data identified two genome-wide significant (p < 5 × 10−8) loci with single nucleotide variant (SNV)-loop diuretic interaction on TG concentrations (including COL11A1). Analysis of AA data identified one genome-wide significant locus adjacent to BMP2 with SNV-loop diuretic interaction on TG concentrations. Trans-ancestry analysis strengthened evidence of association for SNV-loop diuretic interaction at two loci (KIAA1217 and BAALC). There were few significant SNV-thiazide diuretic interaction associations on TG concentrations and for either diuretic on cholesterol concentrations. Several promising loci were identified that may implicate biologic pathways that contribute to adverse metabolic side effects from diuretic therapy

Solar parameters for modeling interplanetary background

The goal of the Fully Online Datacenter of Ultraviolet Emissions (FONDUE) Working Team of the International Space Science Institute in Bern, Switzerland, was to establish a common calibration of various UV and EUV heliospheric observations, both spectroscopic and photometric. Realization of this goal required an up-to-date model of spatial distribution of neutral interstellar hydrogen in the heliosphere, and to that end, a credible model of the radiation pressure and ionization processes was needed. This chapter describes the solar factors shaping the distribution of neutral interstellar H in the heliosphere. Presented are the solar Lyman-alpha flux and the solar Lyman-alpha resonant radiation pressure force acting on neutral H atoms in the heliosphere, solar EUV radiation and the photoionization of heliospheric hydrogen, and their evolution in time and the still hypothetical variation with heliolatitude. Further, solar wind and its evolution with solar activity is presented in the context of the charge exchange ionization of heliospheric hydrogen, and in the context of dynamic pressure variations. Also the electron ionization and its variation with time, heliolatitude, and solar distance is presented. After a review of all of those topics, we present an interim model of solar wind and the other solar factors based on up-to-date in situ and remote sensing observations of solar wind. Results of this effort will further be utilised to improve on the model of solar wind evolution, which will be an invaluable asset in all heliospheric measurements, including, among others, the observations of Energetic Neutral Atoms by the Interstellar Boundary Explorer (IBEX).Comment: Chapter 2 in the planned "Cross-Calibration of Past and Present Far UV Spectra of Solar System Objects and the Heliosphere", ISSI Scientific Report No 12, ed. R.M. Bonnet, E. Quemerais, M. Snow, Springe

Crescimento de eucalipto sob efeito de desfolhamento artificial

O objetivo deste trabalho foi avaliar os efeitos do desfolhamento total, realizado após o plantio e ao longo do primeiro ano de cultivo, sobre o crescimento de Eucalyptus grandis, desde a implantação até ao corte do povoamento. Foram avaliados cinco tratamentos: sem desfolhamento; um desfolhamento aos 56 dias após o plantio (DAP); dois desfolhamentos, aos 56 e 143 DAP; dois desfolhamentos, aos 56 e 267 DAP; e três desfolhamentos, aos 56, 143 e 278 DAP. Foram mensurados os diâmetros do tronco a 1,3 m e a altura total de 60 árvores por tratamento, em oito avaliações, do 21º ao 92º mês de cultivo. O crescimento médio em cada tratamento foi descrito por modelos de regressão não lineares e comparados por testes de identidade para comparar as tendências entre a testemunha e os demais tratamentos. O desfolhamento causou reduções significativas nas taxas de crescimento em diâmetro e altura das plantas, e diminuição expressiva no faturamento ao final da rotação, mesmo quando realizado uma única vez, no início do plantio. Maiores danos, no entanto, foram verificados após consecutivos desfolhamentos ao longo do primeiro ano de cultivo. A manutenção de áreas que tenham sofrido desfolhamento total na fase inicial de plantio pode tornar-se uma medida economicamente inviável.The objective of this work was to evaluate the effects of total defoliation at planting initial stages, and along the first year of cultivation, on Eucalyptus grandis growth, from planting to plantation cut. Five treatments were tested: without defoliation; one defoliation, at 56th day after planting (DAP); two defoliations, at 56th and 143th DAP; two defoliations, at 56th and 267th DAP; and three defoliations, at 56th, 143th and 278th DAP. Trunk diameter at 1.30-m height and the total height of 60 trees were measured from the 21st to the 92th cultivation months. The average growth of each treatment was described by nonlinear models and compared by identity tests in order to estimate the tendencies between control and the other treatments in each variable. Defoliation significantly reduces diameter of the trunk and height growth rates, and expressively decreases the income at the plantation cut. However, greater losses were verified after consecutive defoliation, along the first cultivation year. Maintaining areas that suffered severe defoliations at initial planting stages can become economically unfeasible

Genome-wide meta-analysis of SNP-by9-ACEI/ARB and SNP-by-thiazide diuretic and effect on serum potassium in cohorts of European and African ancestry

We evaluated interactions of SNP-by-ACE-I/ARB and SNP-by-TD on serum potassium (K+) among users of antihypertensive treatments (anti-HTN). Our study included seven European-ancestry (EA) (N = 4835) and four African-ancestry (AA) cohorts (N = 2016). We performed race-stratified, fixed-effect, inverse-variance-weighted meta-analyses of 2.5 million SNP-by-drug interaction estimates; race-combined meta-analysis; and trans-ethnic fine-mapping. Among EAs, we identified 11 significant SNPs (P < 5 × 10 −8 ) for SNP-ACE-I/ARB interactions on serum K+ that were located between NR2F1-AS1 and ARRDC3-AS1 on chromosome 5 (top SNP rs6878413 P = 1.7 × 10 −8 ; ratio of serum K+ in ACE-I/ARB exposed compared to unexposed is 1.0476, 1.0280, 1.0088 for the TT, AT, and AA genotypes, respectively). Trans-ethnic fine mapping identified the same group of SNPs on chromosome 5 as genome-wide significant for the ACE-I/ARB analysis. In conclusion, SNP-by-ACE-I /ARB interaction analyses uncovered loci that, if replicated, could have future implications for the prevention of arrhythmias due to anti-HTN treatment-related hyperkalemia. Before these loci can be identified as clinically relevant, future validation studies of equal or greater size in comparison to our discovery effort are needed

An organelle-specific protein landscape identifies novel diseases and molecular mechanisms

Contains fulltext : 158967.pdf (publisher's version ) (Open Access)Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine