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Search Results: 1 - 10 of 22 matches for " Ruty Keinan "
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"Leaving it to chance"-Passive risk taking in everyday life
Ruty Keinan,Yoella Bereby-Meyer
Judgment and Decision Making , 2012,
Abstract: While risk research focuses on actions that put people at risk, this paper introduces the concept of ``passive risk''---risk brought on or magnified by inaction. We developed a scale measuring personal tendency for passive risk taking (PRT), validated it using a 150 undergraduate student sample, and obtained three factors indicating separate domains of passive risk taking: risk involving resources, medical risks and ethical risks. The scale has criterion validity, as it is correlated with reported passive risk taking in everyday life, and also has high test-retest reliability. While correlated with the DOSPERT scale, the PRT shows divergent validity from classic risk taking constructs like sensation seeking, and convergent validity with tendencies previously not linked to risk taking, such as procrastination and avoidance. The results indicate that passive risk is a separate and unique domain of risk taking, which merits further research to understand the cognitive and motivational mechanism perpetuating it.
Predicting Signatures of “Synthetic Associations” and “Natural Associations” from Empirical Patterns of Human Genetic Variation
Diana Chang,Alon Keinan
PLOS Computational Biology , 2012, DOI: 10.1371/journal.pcbi.1002600
Abstract: Genome-wide association studies (GWAS) have in recent years discovered thousands of associated markers for hundreds of phenotypes. However, associated loci often only explain a relatively small fraction of heritability and the link between association and causality has yet to be uncovered for most loci. Rare causal variants have been suggested as one scenario that may partially explain these shortcomings. Specifically, Dickson et al. recently reported simulations of rare causal variants that lead to association signals of common, tag single nucleotide polymorphisms, dubbed “synthetic associations”. However, an open question is what practical implications synthetic associations have for GWAS. Here, we explore the signatures exhibited by such “synthetic associations” and their implications based on patterns of genetic variation observed in human populations, thus accounting for human evolutionary history –a force disregarded in previous simulation studies. This is made possible by human population genetic data from HapMap 3 consisting of both resequencing and array-based genotyping data for the same set of individuals from multiple populations. We report that synthetic associations tend to be further away from the underlying risk alleles compared to “natural associations” (i.e. associations due to underlying common causal variants), but to a much lesser extent than previously predicted, with both the age and the effect size of the risk allele playing a part in this phenomenon. We find that while a synthetic association has a lower probability of capturing causal variants within its linkage disequilibrium block, sequencing around the associated variant need not extend substantially to have a high probability of capturing at least one causal variant. We also show that the minor allele frequency of synthetic associations is lower than of natural associations for most, but not all, loci that we explored. Finally, we find the variance in associated allele frequency to be a potential indicator of synthetic associations.
Human Population Differentiation Is Strongly Correlated with Local Recombination Rate
Alon Keinan ,David Reich
PLOS Genetics , 2010, DOI: 10.1371/journal.pgen.1000886
Abstract: Allele frequency differences across populations can provide valuable information both for studying population structure and for identifying loci that have been targets of natural selection. Here, we examine the relationship between recombination rate and population differentiation in humans by analyzing two uniformly-ascertained, whole-genome data sets. We find that population differentiation as assessed by inter-continental FST shows negative correlation with recombination rate, with FST reduced by 10% in the tenth of the genome with the highest recombination rate compared with the tenth of the genome with the lowest recombination rate (P?10?12). This pattern cannot be explained by the mutagenic properties of recombination and instead must reflect the impact of selection in the last 100,000 years since human continental populations split. The correlation between recombination rate and FST has a qualitatively different relationship for FST between African and non-African populations and for FST between European and East Asian populations, suggesting varying levels or types of selection in different epochs of human history.
High burden of private mutations due to explosive human population growth and purifying selection
Feng Gao,Alon Keinan
Quantitative Biology , 2014,
Abstract: Recent studies have shown that human populations have experienced a complex demographic history, including a recent epoch of rapid population growth that led to an excess in the proportion of rare genetic variants in humans today. This excess can impact the burden of private mutations for each individual, defined here as the proportion of heterozygous variants in each newly sequenced individual that are novel compared to another large sample of sequenced individuals. We calculated the burden of private mutations predicted by different demographic models, and compared with empirical estimates based on data from the NHLBI Exome Sequencing Project and data from the Neutral Regions (NR) dataset. We observed a significant excess in the proportion of private mutations in the empirical data compared with models of demographic history without a recent epoch of population growth. Incorporating recent growth into the model provides a much improved fit to empirical observations. This phenomenon becomes more marked for larger sample sizes. The proportion of private mutations is additionally increased by purifying selection, which differentially affect mutations of different functional annotations. These results have important implications to the design and analysis of sequencing-based association studies of complex human disease as they pertain to private and very rare variants.
Gender Effects on Acute Heart Failure  [PDF]
Arnon Blum, Rizak Sirchan, Lital Keinan-Boker
International Journal of Clinical Medicine (IJCM) , 2011, DOI: 10.4236/ijcm.2011.23040
Abstract: Background: Congestive heart failure is the leading cause of hospitalization in the elderly. Little is known about gender effect on baseline characteristics and in-hospital outcome in patients admitted with acute heart failure. Our purpose was to study the gender effect on in-hospital mortality in acute heart failure patients. Methods and Results: A prospective study [143 patients, 67 men (73.9 ± 13.8 years old) and 76 women (77.8 ± 10.1 years old) (p = 0.059)] followed in-hospital outcome of patients with acute heart failure admitted to the hospital. Clinical parameters included body mass index (BMI), ankle brachial index (ABI), left ventricular ejection fraction (LVEF), re-admissions within 1 year, and in-hospital mortality. The gender effects that were studied included height, BMI, smoking, coronary artery disease, LVEF and mortality: in total, 9 (6.3%) patients died, of them 8 (10.5%) women and 1 (1.5%) man. Women were shorter (p < 0.001), had a higher BMI (p = 0.053), reported less frequently on current smoking (p < 0.001), had lower prevalence of coronary artery disease (p = 0.016), had a better LVEF (p = 0.02), but still, had a higher mortality rate (p = 0.026). The only variables independently affecting in-hospital mortality in women were height and recurrent admissions. When we tested for the effect of height and recurrent admissions on mortality only among females by a multivariate analysis height inversely and independently affected in-hospital mortality (p = 0.024), as well as recurrent admissions (p = 0.031). Conclusions: In-hospital mortality was significantly higher in women compared with men admitted with acute heart failure. Among females, the only independent variables that affected mortality were low stature and recurrent admissions.
Absorption of Nickel, Chromium, and Iron by the Root Surface of Primary Molars Covered with Stainless Steel Crowns
David Keinan,Eliyahu Mass,Uri Zilberman
International Journal of Dentistry , 2010, DOI: 10.1155/2010/326124
Abstract: Objective. The purpose of this study was to analyze the absorption of metal ions released from stainless steel crowns by root surface of primary molars. Study Design. Laboratory research: The study included 34 primary molars, exfoliated or extracted during routine dental treatment. 17 molars were covered with stainless-steel crowns for more than two years and compared to 17 intact primary molars. Chemical content of the mesial or distal root surface, 1?mm apically to the crown or the cemento-enamel junction (CEJ), was analyzed. An energy dispersive X-ray spectrometer (EDS) was used for chemical analysis. Results. Higher amounts of nickel, chromium, and iron (5-6 times) were found in the cementum of molars covered with stainless-steel crowns compared to intact molars. The differences between groups were highly significant ( ). Significance. Stainless-steel crowns release nickel, chromium, and iron in oral environment, and the ions are absorbed by the primary molars roots. The additional burden of allergenic metals should be reduced if possible. 1. Introduction Nickel sensitivity is common and increasing in prevalence. Nickel was named the “contact allergen of the year” in 2008 by the American Contact Dermatitis Society (ACDS) because of its significant public health importance [1]. Nickel has been the most frequently detected allergen in patch-test populations worldwide, and in North America the prevalence of nickel sensitivity has been increasing steadily since the mid-1980s [2]. Contact dermatitis to nickel can significantly limit an individual's lifestyle, and allergy to nickel has health implications because of the use of nickel in implanted medical devices and in dentistry. Nickel, an abundant natural element, is a hard, silvery-white material in its pure state, which can be combined with other metals, for example, iron, copper, chromium, and zinc, to form alloys and stainless steel. All soil contains nickel and it is accumulated in plants. It is found in meteorites and on the ocean floor and is emitted from volcanoes. Small amounts of nickel are naturally found in drinking water and food. Smokers have a high nickel uptake through their lungs. In humans, most ingested and unabsorbed nickel is excreted in the feces [3]. Nickel absorbed from the gastrointestinal tract is excreted in the urine. Elimination half time averages 28 ± 9 hours [4]. The US Department of Health and Human Services has determined that metallic nickel may be a carcinogen. The International Agency for Research on Cancer has concluded that some nickel compounds and metallic nickel
NRE: a tool for exploring neutral loci in the human genome
Arbiza Leonardo,Zhong Elaine,Keinan Alon
BMC Bioinformatics , 2012, DOI: 10.1186/1471-2105-13-301
Abstract: Background Analyzing regions of the genome where genetic variation is free from the confounding effects of natural selection is essential for many population genetic studies. Several recent studies in humans have stressed the large effect of natural selection at linked neutral sites and have shown that the choice of putatively neutral regions can have a marked effect on estimates of demographic history. Results NRE (Neutral Region Explorer) provides a mechanism for the easy extraction and analysis of nearly neutral regions from the human genome. It can combine many genomic filters, including filters for selection, recombination rate, genetic distance to the nearest gene, percent overlap with annotated regions, and user-provided loci. The program implements a two-step filtering process for greater versatility, allowing users to compile a basic set of neutrality criteria, explore their effect, and use this knowledge to refine filtering. Results can be instantly downloaded in standard formats, along with summary and ranking statistics, or exported to genome browsers such as those from the 1000 Genomes and UCSC. The applicability and value of NRE are demonstrated through an example in the estimation of the ratio of chromosome X-to-autosomal effective population size using different strategies for the selection of neutral regions. Conclusions The combined features of NRE make possible the sort of flexible, rigorous mining and analysis of neutral loci increasingly demanded by population genetic studies. NRE is available at http://nre.cb.bscb.cornell.edu.
Opposing Shear-Induced Forces Dominate Inertial Focusing in Curved Channels and High Reynolds Numbers
Eliezer Keinan,Elishai Ezra,Yaakov Nahmias
Physics , 2015,
Abstract: Inertial focusing is the migration of particles in fluid toward equilibrium, where current theory predicts that shear-induced and wall-induced lift forces are balanced. First reported in 1961, this Segre-Silberberg effect is particularly useful for microfluidic isolation of cells and particles. Interestingly, recent work demonstrated particle focusing at high Reynolds numbers that cannot be explained by current theory. In this work, we show that non-monotonous velocity profiles, such as those developed in curved channels, create peripheral velocity maxima around which opposing shear-induced forces dominate over wall effects. Similarly, entry effects amplified in high Reynolds flow produce an equivalent trapping mechanism in short, straight channels. This new focusing mechanism in the developing flow regime enables a 10-fold miniaturization of inertial focusing devices, while our model corrects long-standing misconceptions about the nature of mechanical forces governing inertial focusing in curved channels.
Gene-Based Testing of Interactions in Association Studies of Quantitative Traits
Li Ma ,Andrew G. Clark,Alon Keinan
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003321
Abstract: Various methods have been developed for identifying gene–gene interactions in genome-wide association studies (GWAS). However, most methods focus on individual markers as the testing unit, and the large number of such tests drastically erodes statistical power. In this study, we propose novel interaction tests of quantitative traits that are gene-based and that confer advantage in both statistical power and biological interpretation. The framework of gene-based gene–gene interaction (GGG) tests combine marker-based interaction tests between all pairs of markers in two genes to produce a gene-level test for interaction between the two. The tests are based on an analytical formula we derive for the correlation between marker-based interaction tests due to linkage disequilibrium. We propose four GGG tests that extend the following P value combining methods: minimum P value, extended Simes procedure, truncated tail strength, and truncated P value product. Extensive simulations point to correct type I error rates of all tests and show that the two truncated tests are more powerful than the other tests in cases of markers involved in the underlying interaction not being directly genotyped and in cases of multiple underlying interactions. We applied our tests to pairs of genes that exhibit a protein–protein interaction to test for gene-level interactions underlying lipid levels using genotype data from the Atherosclerosis Risk in Communities study. We identified five novel interactions that are not evident from marker-based interaction testing and successfully replicated one of these interactions, between SMAD3 and NEDD9, in an independent sample from the Multi-Ethnic Study of Atherosclerosis. We conclude that our GGG tests show improved power to identify gene-level interactions in existing, as well as emerging, association studies.
Experimental validation and physical modelling of vocal folds pathologies
Nicolas Ruty,Claire Brutel,Xavier Pelorson,Annemie Van Hirtum
Physics , 2007,
Abstract: Voiced sounds involve self-sustained vocal folds oscillations due to the interaction between the airflow and the vocal folds. Common vocal folds pathologies like polyps and anatomical asymmetry degrade the mechanical vocal fold properties and consequently disturb the normal oscillation pattern resulting in an abnormal sound production. Treatment of voice abnormalities would benefit from an improved understanding between the pathology and the resulting oscillation pattern which motivates physical vocal folds modelling. The current study applies a theoretical vocal folds model to vocal folds pathologies. The theoretical vocal folds model is validated using an experimental set-up simulating the human phonatory apparatus. It consists in a pressure reservoir, a self-oscillating latex replica of the vocal folds and an acoustical resonator. The effects of pathologies are simulated by modifying the replica's geometry, elasticity, and homogeneity under controlled experimental conditions. In general, we observed a close match between measurements and theoretical predictions, which is all the more surprising considering the crudeness of the theoretical model
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