Showing papers by "University of Zagreb published in 2010"
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Elizabeth K. Speliotes1, Elizabeth K. Speliotes2, Cristen J. Willer3, Sonja I. Berndt +410 more•Institutions (86)
TL;DR: Genetic loci associated with body mass index map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor, which may provide new insights into human body weight regulation.
Abstract: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
2,632 citations
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TL;DR: It is demonstrated that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
Abstract: Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
2,022 citations
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TL;DR: It is shown that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait, and indicates that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
1,768 citations
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University of Milan1, University of Siena2, Marche Polytechnic University3, Sapienza University of Rome4, University of Nantes5, University of Pécs6, Umeå University7, Newcastle University8, University of Greifswald9, Ludwig Maximilian University of Munich10, University of Paris11, Case Western Reserve University12, University of Zagreb13, University of Florida14, Indiana University15, Leeds General Infirmary16, University of Liège17, University of Groningen18, Tel Aviv University19, Medical University of Warsaw20, University of Colorado Denver21, Lille University of Science and Technology22, Erasmus University Rotterdam23, University of Iowa24
TL;DR: This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants.
Abstract: The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.
1,267 citations
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Hacettepe University1, Istituto Giannina Gaslini2, Aarhus University3, Rambam Health Care Campus4, Istanbul University5, Catholic University of the Sacred Heart6, University of São Paulo7, Sheba Medical Center8, Seconda Università degli Studi di Napoli9, University of Latvia10, Rio de Janeiro State University11, University of Zagreb12, University of Chieti-Pescara13, Alfaisal University14, Saint Petersburg State Pediatric Medical University15, Charité16, Children's Memorial Hospital17, Autonomous University of Madrid18, University of Tartu19, Innsbruck Medical University20, Tbilisi State Medical University21, University of Genoa22
TL;DR: The previously proposed classification criteria for Henoch–Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (C-WG) and c-Takayasu arteritis ( c-TA) are validated.
Abstract: Objectives To validate the previously proposed classification criteria for Henoch–Schonlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA). Methods Step 1: retrospective/prospective web-data collection for children with HSP, c-PAN, c-WG and c-TA with age at diagnosis ≤18 years. Step 2: blinded classification by consensus panel of a representative sample of 280 cases. Step 3: statistical (sensitivity, specificity, area under the curve and κ-agreement) and nominal group technique consensus evaluations. Results 827 patients with HSP, 150 with c-PAN, 60 with c-WG, 87 with c-TA and 52 with c-other were compared with each other. A patient was classified as HSP in the presence of purpura or petechiae (mandatory) with lower limb predominance plus one of four criteria: (1) abdominal pain; (2) histopathology (IgA); (3) arthritis or arthralgia; (4) renal involvement. Classification of c-PAN required a systemic inflammatory disease with evidence of necrotising vasculitis OR angiographic abnormalities of medium-/small-sized arteries (mandatory criterion) plus one of five criteria: (1) skin involvement; (2) myalgia/muscle tenderness; (3) hypertension; (4) peripheral neuropathy; (5) renal involvement. Classification of c-WG required three of six criteria: (1) histopathological evidence of granulomatous inflammation; (2) upper airway involvement; (3) laryngo-tracheo-bronchial involvement; (4) pulmonary involvement (x-ray/CT); (5) antineutrophilic cytoplasmic antibody positivity; (6) renal involvement. Classification of c-TA required typical angiographic abnormalities of the aorta or its main branches and pulmonary arteries (mandatory criterion) plus one of five criteria: (1) pulse deficit or claudication; (2) blood pressure discrepancy in any limb; (3) bruits; (4) hypertension; (5) elevated acute phase reactant. Conclusion European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society propose validated classification criteria for HSP, c-PAN, c-WG and c-TA with high sensitivity/specificity.
1,063 citations
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University of Basel1, Radboud University Nijmegen2, University of Padua3, Complutense University of Madrid4, University of Paris5, University of Zurich6, University of Bari7, Lithuanian University of Health Sciences8, University of Florence9, Russian Academy10, Rambam Health Care Campus11, University of Regensburg12, Charité13, University of the Witwatersrand14, Johns Hopkins University15, University of Coimbra16, University of Verona17, Lund University18, University of Ljubljana19, Utrecht University20, University of Pécs21, Medical University of Vienna22, University of Debrecen23, Sapienza University of Rome24, University of Geneva25, University of Silesia in Katowice26, University College London27, University of Tübingen28, Military Medical Academy29, Lille University of Science and Technology30, University of Michigan31, Iuliu Hațieganu University of Medicine and Pharmacy32, Charles University in Prague33, University of Zagreb34
TL;DR: Disease-related causes, in particular pulmonary fibrosis, PAH and cardiac causes, accounted for the majority of deaths in SSc.
Abstract: Objectives To determine the causes and predictors of mortality in systemic sclerosis (SSc). Methods Patients with SSc (n=5860) fulfilling the American College of Rheumatology criteria and prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) cohort were analysed. EUSTAR centres completed a structured questionnaire on cause of death and comorbidities. Kaplan-Meier and Cox proportional hazards models were used to analyse survival in SSc subgroups and to identify predictors of mortality. Results Questionnaires were obtained on 234 of 284 fatalities. 55% of deaths were attributed directly to SSc and 41% to non-SSc causes; in 4% the cause of death was not assigned. Of the SSc-related deaths, 35% were attributed to pulmonary fibrosis, 26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes (mainly heart failure and arrhythmias). Among the non-SSc-related causes, infections (33%) and malignancies (31%) were followed by cardiovascular causes (29%). Of the non-SSc-related fatalities, 25% died of causes in which SSc-related complications may have participated (pneumonia, sepsis and gastrointestinal haemorrhage). Independent risk factors for mortality and their HR were: proteinuria (HR 3.34), the presence of PAH based on echocardiography (HR 2.02), pulmonary restriction (forced vital capacity below 80% of normal, HR 1.64), dyspnoea above New York Heart Association class II (HR 1.61), diffusing capacity of the lung (HR 1.20 per 10% decrease), patient age at onset of Raynaud's phenomenon (HR 1.30 per 10 years) and the modified Rodnan skin score (HR 1.20 per 10 score points). Conclusion Disease-related causes, in particular pulmonary fibrosis, PAH and cardiac causes, accounted for the majority of deaths in SSc.
1,010 citations
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Iris M. Heid1, Anne U. Jackson2, Joshua C. Randall3, Tthomas W. Winkler1 +352 more•Institutions (90)
TL;DR: A meta-analysis of genome-wide association studies for WHR adjusted for body mass index provides evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
Abstract: Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
869 citations
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TL;DR: An up-to-date review and a new classification of the existingShape reconstruction using coded structured light techniques and their potentials are presented.
782 citations
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Johns Hopkins University1, University of Freiburg2, University of Lübeck3, University of Regensburg4, University of Washington5, University of Maryland, Baltimore6, Washington University in St. Louis7, Boston University8, University of Iceland9, National Institutes of Health10, Memorial Hospital of South Bend11, Erasmus University Rotterdam12, University of Greifswald13, McMaster University14, Mayo Clinic15, University of Mainz16, Wake Forest University17, Harvard University18, University of Basel19, Swiss Tropical and Public Health Institute20, Innsbruck Medical University21, Leipzig University22, Western General Hospital23, University of Texas Health Science Center at Houston24, Cedars-Sinai Medical Center25, University of Pittsburgh26, Ludwig Maximilian University of Munich27, University of Ulm28, University of Edinburgh29, University of Split30, University of Zagreb31, Uppsala University32, University of Kiel33, University of London34, University of Oxford35, Amgen36, University of Michigan37, University of Geneva38, Capital Medical University39, University of California, San Francisco40, Heidelberg University41
TL;DR: The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry to identify new susceptibility loci for reduced renal function as estimated by serum creatinine, serum cystatin c and CKD.
Abstract: Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m(2); n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide-significant loci (P < 5 x 10(-8)) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.
756 citations
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University of Oxford1, GlaxoSmithKline2, Imperial College London3, University of Pennsylvania4, University of Lausanne5, Medical Research Council6, Wellcome Trust Sanger Institute7, University of Cambridge8, The Heart Research Institute9, University of California, San Francisco10, University of Oulu11, University of Ottawa12, University of Toronto13, King's College London14, University of Dundee15, University of Bergen16, Max Planck Society17, Ludwig Maximilian University of Munich18, University of Mainz19, Innsbruck Medical University20, University of Zagreb21, University of Edinburgh22, MedStar Washington Hospital Center23, University of Kiel24, National Research Council25, National Institutes of Health26, University of Texas MD Anderson Cancer Center27, University of Aberdeen28, University of Michigan29, University of Greifswald30, University of Split31, University of Leicester32, University of Leeds33, Guy's Hospital34, Queen Mary University of London35, University of Glasgow36
TL;DR: The Oxford-GlaxoSmithKline study (Ox-GSK) as discussed by the authors performed a genome-wide meta-analysis of SNP association with smoking-related behavioral traits and found an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19) that includes CHRNA5, CHRNA3 and CHRNB4.
Abstract: Smoking is a leading global cause of disease and mortality. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.
568 citations
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University of Leicester1, University of Nottingham2, Queen Mary University of London3, Medical Research Council4, Imperial College London5, King's College London6, Western General Hospital7, Uppsala University8, Wellcome Trust Sanger Institute9, University of Bristol10, St George's, University of London11, University of Helsinki12, University of Jyväskylä13, National Institutes of Health14, University of Zurich15, University of Split16, University of Zagreb17, University of Edinburgh18, University of Greifswald19, University of Gothenburg20, University of Western Australia21, Sir Charles Gairdner Hospital22, University College London23, University of London24, Glenfield Hospital25, University of Dundee26, National Institute for Health Research27, Southampton General Hospital28, Pasteur Institute29, University of Basel30, AstraZeneca31, University of Tampere32, University of St Andrews33, Health Protection Agency34
TL;DR: Genome-wide association with forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in the SpiroMeta consortium offers mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.
Abstract: Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.
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TL;DR: A meta-analysis of 32 genome-wide association studies in 87,802 women of European descent found 30 new menarche loci and found suggestive evidence for a further 10 loci, including four previously associated with body mass index and three in or near genes implicated in hormonal regulation.
Abstract: To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
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TL;DR: In this article, a complete overview of the work done so far on the research and implementation of dividing wall columns can be found, from early ideas on thermal coupling of distillation columns to practical issues that needed to be solved for their successful implementation.
Abstract: Dividing wall column (DWC) is a single shell, fully thermally coupled distillation column capable of separating mixtures of three or more components into high purity products. Compared to conventional columns-in-series and/or in-parallel configurations a DWC requires much less energy, capital and space. This makes DWC to something that corresponds with the present day idea of sustainable process technology. Based on published papers and patent literature this paper aims to give a complete overview of the work done so far on the research and implementation of DWCs, from early ideas on thermal coupling of distillation columns to practical issues that needed to be solved for their successful implementation. Approaches to short-cut and rigorous simulation, optimization, and control are highlighted, with particular focus on column internals and dimensioning, which is only conceptually considered in academic publications. A survey of relevant patents is included providing information on equipment innovations and application areas of industrial interest. Finally authors look at what is needed on research and engineering side to enable maximization of potential gains by building DWCs for obtaining four or even more products containing two or more partition walls in parallel, which is something not yet attempted in industrial practice.
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TL;DR: Clinical relevant data is presented on prenatal development of thalamocortical connections in the human brain based on extensive Zagreb Neuroembryological Collection, including more than 500 prenatal human brains stained with various classical neurohistological, as well as modern histochemical and immunohistochemical methods.
Abstract: UNLABELLED The aim of this review is to present clinically relevant data on prenatal development of thalamocortical connections in the human brain. The analysis is based on extensive Zagreb Neuroembryological Collection, including more than 500 prenatal human brains stained with various classical neurohistological, as well as modern histochemical and immunohistochemical methods. The connection of thalamocortical axons during the 'waiting' period with transient cortical subplate zone and subsequent synaptic engagement in the cortical plate is the main connectivity event in the late foetus and preterm infant. This connectivity is the structural substrate for the endogeneous subplate and sensory-driven circuitry generating transient electrical phenomena and may represent a transient network in the developmental history of consciousness. CONCLUSION Findings presented in this review should be considered in the management of pain in preterm infants, in searching for the vulnerability of the subplate zone in diagnostic procedures using the in vivo MRI and in revealing the developmental origin of cognitive and mental disorders.
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TL;DR: Striking evidences implicating LPO in foetal vascular dysfunction occurring in pre-eclampsia, in renal and liver diseases, as well as their role as cause and consequence to cancer development are addressed.
Abstract: Lipid peroxidation (LPO) product accumulation in human tissues is a major cause of tissular and cellular dysfunction that plays a major role in ageing and most age-related and oxidative stress-related diseases. The current evidence for the implication of LPO in pathological processes is discussed in this review. New data and literature review are provided evaluating the role of LPO in the pathophysiology of ageing and classically oxidative stress-linked diseases, such as neurodegenerative diseases, diabetes and atherosclerosis (the main cause of cardiovascular complications). Striking evidences implicating LPO in foetal vascular dysfunction occurring in pre-eclampsia, in renal and liver diseases, as well as their role as cause and consequence to cancer development are addressed.
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University of Washington1, Erasmus University Rotterdam2, National Institutes of Health3, Harvard University4, University Medical Center Groningen5, Ludwig Maximilian University of Munich6, University of Minnesota7, University of Lübeck8, University of Glasgow9, Medical Research Council10, University of Iceland11, University of Zagreb12, New York University13, Boston University14, Technische Universität München15, Johns Hopkins University16, Queen Mary University of London17, University of Edinburgh18, Utrecht University19, Johns Hopkins University School of Medicine20, Greifswald University Hospital21, Wake Forest University22, St Thomas' Hospital23, University of Texas Health Science Center at Houston24, Cedars-Sinai Medical Center25, Group Health Research Institute26, University of Ferrara27, University of Dundee28, University of California, Los Angeles29, University of Split30, St George's, University of London31, Glenfield Hospital32, University of Leicester33
TL;DR: It is demonstrated that SCN10A, a candidate gene at the most significantly associated locus in this study, is expressed in the mouse ventricular conduction system, and treatment with a selective SCN 10A blocker prolongs QRS duration.
Abstract: The QRS interval, from the beginning of the Q wave to the end of the S wave on an electrocardiogram, reflects ventricular depolarization and conduction time and is a risk factor for mortality, sudden death and heart failure. We performed a genome-wide association meta-analysis in 40,407 individuals of European descent from 14 studies, with further genotyping in 7,170 additional Europeans, and we identified 22 loci associated with QRS duration (P < 5 × 10(-8)). These loci map in or near genes in pathways with established roles in ventricular conduction such as sodium channels, transcription factors and calcium-handling proteins, but also point to previously unidentified biologic processes, such as kinase inhibitors and genes related to tumorigenesis. We demonstrate that SCN10A, a candidate gene at the most significantly associated locus in this study, is expressed in the mouse ventricular conduction system, and treatment with a selective SCN10A blocker prolongs QRS duration. These findings extend our current knowledge of ventricular depolarization and conduction.
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TL;DR: Surfactants in the Environment Surfactants are a diverse group of chemicals that are best known for their wide use in detergents and other cleaning products and most of them end up dispersed in different environmental compartments such as soil, water or sediment.
Abstract: Surfactants are a diverse group of chemicals that are best known for their wide use in detergents and other cleaning products. After use, residual surfactants are discharged into sewage systems or directly into surface waters, and most of them end up dispersed in different environmental compartments such as soil, water or sediment. The toxic effects of surfactants on various aquatic organisms are well known. In general, surfactants are present in the environment at levels below toxicity and in Croatia below the national limit. Most surfactants are readily biodegradable and their amount is greatly reduced with secondary treatment in wastewater treatment plants. The highest concern is the release of untreated wastewater or wastewater that has undergone primary treatment alone. The discharge of wastewater polluted with massive quantities of surfactants could have serious effects on the ecosystem. Future studies of surfactant toxicities and biodegradation are necessary to withdraw highly toxic and non-biodegradable compounds from commercial use and replace them with more environmentally friendly ones.
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University of California, San Francisco1, Centre national de la recherche scientifique2, Fred Hutchinson Cancer Research Center3, University of Zagreb4, University of Aberdeen5, New York University6, Pfizer7, University of British Columbia8, Katholieke Universiteit Leuven9, University of Sheffield10
TL;DR: In postmenopausal women with osteoporosis, lasofoxifene at a dose of 0.5 mg per day was associated with reduced risks of nonvertebral and vertebral fractures, ER-positive breast cancer, coronary heart disease, and stroke but an increased risk of venous thromboembolic events.
Abstract: Background The effects of lasofoxifene on the risk of fractures, breast cancer, and cardiovascular disease are uncertain. Methods In this randomized trial, we assigned 8556 women who were between the ages of 59 and 80 years and had a bone mineral density T score of –2.5 or less at the femoral neck or spine to receive once-daily lasofoxifene (at a dose of either 0.25 mg or 0.5 mg) or placebo for 5 years. Primary end points were vertebral fractures, estrogen receptor (ER)–positive breast cancer, and nonvertebral fractures; secondary end points included major coronary heart disease events and stroke. Results Lasofoxifene at a dose of 0.5 mg per day, as compared with placebo, was associated with reduced risks of vertebral fracture (13.1 cases vs. 22.4 cases per 1000 person-years; hazard ratio, 0.58; 95% confidence interval [CI], 0.47 to 0.70), nonvertebral fracture (18.7 vs. 24.5 cases per 1000 person-years; hazard ratio, 0.76; 95% CI, 0.64 to 0.91), ER-positive breast cancer (0.3 vs. 1.7 cases per 1000 perso...
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B. I. Abelev1, Madan M. Aggarwal2, Zubayer Ahammed3, A. V. Alakhverdyants4 +372 more•Institutions (49)
TL;DR: In this paper, a three-particle mixed-harmonic azimuthal correlator is investigated, which is a P-even observable, but directly sensitive to the charge-separation effect.
Abstract: Parity (P)-odd domains, corresponding to nontrivial topological solutions of the QCD vacuum, might be created during relativistic heavy-ion collisions. These domains are predicted to lead to charge separation of quarks along the orbital momentum of the system created in noncentral collisions. To study this effect, we investigate a three-particle mixed-harmonics azimuthal correlator which is a P-even observable, but directly sensitive to the charge-separation effect. We report measurements of this observable using the STAR detector in Au + Au and Cu + Cu collisions at root s(NN) = 200 and 62 GeV. The results are presented as a function of collision centrality, particle separation in rapidity, and particle transverse momentum. A signal consistent with several of the theoretical expectations is detected in all four data sets. We compare our results to the predictions of existing event generators and discuss in detail possible contributions from other effects that are not related to P violation.
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Madan M. Aggarwal1, Zubayer Ahammed2, A. V. Alakhverdyants3, I. G. Alekseev +380 more•Institutions (50)
TL;DR: From the measurements at the three beam energies, no evidence for a critical point in the QCD phase diagram for μB below 200 MeV is found and the products κσ2 and Sσ are constant as functions of collision centrality.
Abstract: 200 GeV corresponding to baryon chemical potentials (mu(B)) between 200 and 20 MeV. Our measurements of the products kappa sigma(2) and S sigma, which can be related to theoretical calculations sensitive to baryon number susceptibilities and long-range correlations, are constant as functions of collision centrality. We compare these products with results from lattice QCD and various models without a critical point and study the root s(NN) dependence of kappa sigma(2). From the measurements at the three beam energies, we find no evidence for a critical point in the QCD phase diagram for mu(B) below 200 MeV.
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TL;DR: The main goal of this review is to summarize the present understanding of CSF formation and compare this understanding to contradictory experimental results that have been obtained so far, and to try to offer a physiological explanation by which these contradictions could be avoided.
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TL;DR: In this paper, the effect of the high power ultrasound of 24 kHz frequency on rheological and some physical properties of corn starch was examined, and the results showed a decrease in enthalpy of gelatinization and a significant decrease in consistency coefficient.
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TL;DR: It is suggested that the NSSS may be a useful tool for assessing sexual satisfaction regardless of a person's gender, sexual orientation, and relationship status.
Abstract: The development and bicultural validation of the New Sexual Satisfaction Scale (NSSS)--a 20 item, multidimensional, composite measure of sexual satisfaction--is presented. The development of the scale was based on a five-dimension, conceptual model that emphasized the importance of multiple domains of sexual behavior including sexual sensations, sexual awareness and focus, sexual exchange, emotional closeness, and sexual activity. Scale construction and validation were carried out using seven independent samples with over 2,000 participants aged 18 to 55 in Croatia and the United States. Primary data collection was completed using online survey tools. Analyses did not confirm the proposed conceptual framework but suggested a two-dimensional structure focusing on self ("ego-centered") and the other (a "partner- and sexual activity-centered" factor) domains, each containing items representing all five conceptual dimensions. Scale reliability (k = 20) was satisfactory for all samples, and construct validity was confirmed in both cultures. The NSSS was also found to have acceptable one-month stability. It is suggested that the NSSS may be a useful tool for assessing sexual satisfaction regardless of a person's gender, sexual orientation, and relationship status.
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TL;DR: A clinical practice guide to enteral nutrition support is provided, urging the development and application of procedural protocols that include scrupulous attention to hygiene, as well as regular monitoring by a multidisciplinary nutrition support team to minimise the risk of EN-associated complications.
Abstract: Enteral nutrition support (ENS) involves both the delivery of nutrients via feeding tubes and the provision of specialised oral nutritional supplements. ENS is indicated in a patient with at least a partially functioning digestive tract when oral intake is inadequate or intake of normal food is inappropriate to meet the patients' needs. The aim of this comment by the Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition is to provide a clinical practice guide to ENS, based on the available evidence and the clinical expertise of the authors. Statements and recommendations are presented, and future research needs highlighted, with a particular emphasis placed on a practical approach to ENS.Among the wide array of enteral formulations, standard polymeric feeds based on cow's-milk protein with fibre and age adapted for energy and nutrient content are suitable for most paediatric patients. Whenever possible, intragastric is preferred to postpyloric delivery of nutrients, and intermittent feeding is preferred to continuous feeding because it is more physiological. An anticipated duration of enteral nutrition (EN) exceeding 4 to 6 weeks is an indication for gastrostomy or enterostomy. Among the various gastrostomy techniques available, percutaneous endoscopic gastrostomy is currently the first option. In general, both patients and caregivers express satisfaction with this procedure, although it is associated with a number of well-recognised complications. We strongly recommend the development and application of procedural protocols that include scrupulous attention to hygiene, as well as regular monitoring by a multidisciplinary nutrition support team to minimise the risk of EN-associated complications.
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29 Apr 2010TL;DR: Boundary potential theory for Schr#x00F6 dinger operators based on fractional Laplacian is proposed in this article, where the potential theory of subordinate Brownian motion is applied to the potential potential theory.
Abstract: Boundary Potential Theory for Schr#x00F6 dinger Operators Based on Fractional Laplacian.- Nontangential Convergence for #x03B1 -harmonic Functions.- Eigenvalues and Eigenfunctions for Stable Processes.- Potential Theory of Subordinate Brownian Motion.
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B. I. Abelev1, Madan M. Aggarwal2, Zubayer Ahammed3, A. V. Alakhverdyants4 +387 more•Institutions (50)
TL;DR: The authors reported the observation of antihypertritons-comprising an antiproton, an antineutron, and an antilambda hyperon-produced by colliding gold nuclei at high energy.
Abstract: Nuclear collisions recreate conditions in the universe microseconds after the Big Bang. Only a very small fraction of the emitted fragments are light nuclei, but these states are of fundamental interest. We report the observation of antihypertritons-comprising an antiproton, an antineutron, and an antilambda hyperon-produced by colliding gold nuclei at high energy. Our analysis yields 70 +/- 17 antihypertritons (3/Lambda(H) over bar) and 157 +/- 30 hypertritons ((3)(Lambda)H). The measured yields of (3)(Lambda)H (3/Lambda(H) over bar) and (3)He ((3)(He) over bar) are similar, suggesting an equilibrium in coordinate and momentum space populations of up, down, and strange quarks and antiquarks, unlike the pattern observed at lower collision energies. The production and properties of antinuclei, and of nuclei containing strange quarks, have implications spanning nuclear and particle physics, astrophysics, and cosmology.
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TL;DR: The potential of using bacteriocins of lactic acid bacteria, primarily used as biopreservatives, represents a perspective, alternative antimicrobial strategy for continuously increasing problem with antibiotic resistance.
Abstract: Summary The antimicrobial activity of industrially important lactic acid bacteria as starter cultures and probiotic bacteria is the main subject of this review. This activity has been attributed to the production of metabolites such as organic acids (lactic and acetic acid), hydrogen peroxide, ethanol, diacetyl, acetaldehyde, acetoine, carbon dioxide, reuterin, reutericyclin and bacteriocins. The potential of using bacteriocins of lactic acid bacteria, primarily used as biopreservatives, represents a perspective, alternative antimicrobial strategy for continuously increasing problem with antibiotic resistance. Another strategy in resolving this problem is an application of probiotics for different gastrointestinal and urogenital infection therapies.
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TL;DR: In this paper, the authors adopt the utilitarian view of volunteering as a starting point: they posit that for an undergraduate student population volunteering is motivated by career enhancing and job prospects, and they hypothesize that in those countries where volunteering signals positive characteristics of students and helps advance their careers, their volunteer participation will be higher.
Abstract: This research adopts the utilitarian view of volunteering as a starting point: we posit that for an undergraduate student population volunteering is motivated by career enhancing and job prospects. We hypothesize that in those countries where volunteering signals positive characteristics of students and helps advance their careers, their volunteer participation will be higher. Furthermore, regardless of the signaling value of volunteering, those students who volunteer for utilitarian reasons will be more likely to volunteer but will exhibit less time-intensive volunteering. Using survey data from 12 countries (n = 9,482), we examine our hypotheses related to motivations to volunteer, volunteer participation, and country differences. Findings suggest that students motivated to volunteer for building their resumes do not volunteer more than students with other motives. However, in countries with a positive signaling value of volunteering, volunteering rates are significantly higher. As expected, students motivated by resume building motivations have a lower intensity of volunteering.
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TL;DR: A novel approach combining genome-wide association and high-throughput glycomics analysis of 2,705 individuals in three population cohorts showed that common variants in the Hepatocyte Nuclear Factor 1α (HNF1α) and fucosyltransferase genes FUT6 and FUT8 influence N-glycan levels in human plasma.
Abstract: Over half of all proteins are glycosylated, and alterations in glycosylation have been observed in numerous physiological and pathological processes. Attached glycans significantly affect protein function; but, contrary to polypeptides, they are not directly encoded by genes, and the complex processes that regulate their assembly are poorly understood. A novel approach combining genome-wide association and high-throughput glycomics analysis of 2,705 individuals in three population cohorts showed that common variants in the Hepatocyte Nuclear Factor 1α (HNF1α) and fucosyltransferase genes FUT6 and FUT8 influence N-glycan levels in human plasma. We show that HNF1α and its downstream target HNF4α regulate the expression of key fucosyltransferase and fucose biosynthesis genes. Moreover, we show that HNF1α is both necessary and sufficient to drive the expression of these genes in hepatic cells. These results reveal a new role for HNF1α as a master transcriptional regulator of multiple stages in the fucosylation process. This mechanism has implications for the regulation of immunity, embryonic development, and protein folding, as well as for our understanding of the molecular mechanisms underlying cancer, coronary heart disease, and metabolic and inflammatory disorders.
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TL;DR: A broad variation in the antibacterial properties of investigated essential oils was observed, while Ocimum americanum and OCimum x citriodorum essential oils were the most effective against Enterococcus faecalis, Enterococus faecium, P. vulgaris, S. aureus and S. epidermis.