Comparison of Strategies to Detect Epistasis from eQTL Data.

Genome-wide association studies have been instrumental in identifying genetic variants associated with complex traits such as human disease or gene expression phenotypes. It has been proposed that extending existing analysis methods by considering interactions between pairs of loci may uncover additional genetic effects. However, the large number of possible two-marker tests presents significant computational and statistical challenges. Although several strategies to detect epistasis effects have been proposed and tested for specific phenotypes, so far there has been no systematic attempt to compare their performance using real data. We made use of thousands of gene expression traits from linkage and eQTL studies, to compare the performance of different strategies. We found that using information from marginal associations between markers and phenotypes to detect epistatic effects yielded a lower false discovery rate (FDR) than a strategy solely using biological annotation in yeast, whereas results from human data were inconclusive. For future studies whose aim is to discover epistatic effects, we recommend incorporating information about marginal associations between SNPs and phenotypes instead of relying solely on biological annotation. Improved methods to discover epistatic effects will result in a more complete understanding of complex genetic effects.

Risk Mitigation Strategies for Operations and Maintenance Activities, Final Report, April 2012

The objective of this research was to investigate the application of integrated risk modeling to operations and maintenance activities, specifically moving operations, such as pavement testing, pavement marking, painting, snow removal, shoulder work, mowing, and so forth. The ultimate goal is to reduce the frequency and intensity of loss events (property damage, personal injury, and fatality) during operations and maintenance activities. This report includes a literature review that identifies the current and common practices adopted by different state departments of transportation (DOTs) and other transportation agencies for safe and efficient highway operations and maintenance (O/M) activities. The final appendix to the report includes information for eight innovative O/M risk mitigation technologies/equipment and covers the following for these technologies/equipment: Appropriate conditions for deployment Performance/effectiveness, depending on hazard/activity Cost to purchase Cost to operate and maintain Availability (resources and references)

Troubles de la mémoire chez la personne agée: que faire au cabinet [Cognitive impairment in elderly patients: what to do in primary care?].

In Switzerland, each year there are about 25000 new patients suffering from dementia (one new case every 20 minutes!). Currently, recognition of cognitive impairment and dementia diagnoses remain essentially based on clinical features. For the primary care provider, a 4-step approach based on a) history, b) collateral information provided by a knowledgeable relative, c) a standardized brief cognitive screening instrument, and d) simple laboratory tests will identify most older persons suffering from dementia. Unclear situations benefit from an assessment in a memory clinic.

Security strategies and equilibria in multiobjetives matrix games

Multiobjective matrix games have been traditionally analyzed from two different points of view: equiibrium concepts and security strategies. This paper is based upon the idea that both players try to reach equilibrium points playing pairs of security strategies, as it happens in scalar matrix games. We show conditions guaranteeing the existence of equilibria in security strategies, named security equilibria

Buy-and-Hold Strategies and Comonotonic Approximations

[cat] En aquest article estudiem estratègies “comprar i mantenir” per a problemes d’optimitzar la riquesa final en un context multi-període. Com que la riquesa final és una suma de variables aleatòries dependents, on cadascuna d’aquestes correspon a una quantitat de capital que s’ha invertit en un actiu particular en una data determinada, en primer lloc considerem aproximacions que redueixen l’aleatorietat multivariant al cas univariant. A continuació, aquestes aproximacions es fan servir per determinar les estratègies “comprar i mantenir” que optimitzen, per a un nivell de probabilitat donat, el VaR i el CLTE de la funció de distribució de la riquesa final. Aquest article complementa el treball de Dhaene et al. (2005), on es van considerar estratègies de reequilibri constant.

The switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of cognitive deficits. A pilot study in individuals with schizophrenia.

Background: Atypical antipsychotics provide better control of the negative and affective symptoms of schizophrenia when compared with conventional neuroleptics; nevertheless, their heightened ability to improve cognitive dysfunction remains a matter of debate. This study aimed to examine the changes in cognition associated with long-term antipsychotic treatment and to evaluate the effect of the type of antipsychotic (conventional versus novel antipsychotic drugs) on cognitive performance over time. Methods: In this naturalistic study, we used a comprehensive neuropsychological battery of tests to assess a sample of schizophrenia patients taking either conventional (n = 13) or novel antipsychotics (n = 26) at baseline and at two years after. Results: Continuous antipsychotic treatment regardless of class was associated with improvement on verbal fluency, executive functions, and visual and verbal memory. Patients taking atypical antipsychotics did not show greater cognitive enhancement over two years than patients taking conventional antipsychotics. Conclusions Although long-term antipsychotic treatment slightly improved cognitive function, the switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of these cognitive deficits.

Early antifungal intervention strategies in ICU patients.

PURPOSE OF REVIEW: Despite progress in the understanding of the pathophysiology of invasive candidiasis, and the development of new classes of well tolerated antifungals, invasive candidiasis remains a disease difficult to diagnose, and associated with significant morbidity and mortality. Early antifungal treatment may be useful in selected groups of patients who remain difficult to identify prospectively. The purpose of this review is to summarize the recent development of risk-identification strategies targeting early identification of ICU patients susceptible to benefit from preemptive or empirical antifungal treatment. RECENT FINDINGS: Combinations of different risk factors are useful in identifying high-risk patients. Among the many risk factors predisposing to invasive candidiasis, colonization has been identified as one of the most important. In contrast to prospective surveillance of the dynamics of colonization (colonization index), integration of clinical colonization status in risk scores models significantly improve their accuracy in identifying patients at risk of invasive candidiasis. SUMMARY: To date, despite limited prospective validation, clinical models targeted at early identification of patients at risk to develop invasive candidiasis represent a major advance in the management of patients at risk of invasive candidiasis. Moreover, large clinical studies using such risk scores or predictive rules are underway.

Mating frequency of ant queens with alternative dispersal strategies, as revealed by microsatellite analysis of sperm

In social Hymenoptera (ants, bees, and wasps), the number of males that mate with the same queen affects social and genetic organization of the colony. However, the selective forces leading to single mating in certain conditions and multiple mating in others remain enigmatic. In this study, I investigated whether queens of the wood ant Formica paralugubris adopting different dispersal strategies varied in their mating frequency (the number of males with whom they mated). The frequency of multiple mating was determined by using microsatellite markers to genotype the sperm stored in the spermatheca of queens, and the validity of this method was confirmed by analysing mother-offspring combinations obtained from experimental single-queen colonies. Dispersing queens, which may found new colonies, did not mate with more males than queens that stayed within polygynous colonies, where the presence of numerous reproductive individuals ensured a high level of genetic diversity. Hence, this study provides no support to the hypotheses that multiple mating is beneficial because it increases genetic variability within colonies. Most of the F. paralugubris queens mated with a single male, whatever their dispersal strategy and life history. Moreover, multiple mating had little effect on colony genetic structure: the effective mating frequency was 1.11 when calculated from within-brood relatedness, and 1.13 when calculated from the number of mates detected in the sperm. Hence, occasional multiple mating by F. paralugubris queens may have no adaptive significance.