An efficient algorithm to perform multiple testing in epistasis screening

Background: Research in epistasis or gene-gene interaction detection for human complex traits has grown over the last few years. It has been marked by promising methodological developments, improved translation efforts of statistical epistasis to biological epistasis and attempts to integrate different omics information sources into the epistasis screening to enhance power. The quest for gene-gene interactions poses severe multiple-testing problems. In this context, the maxT algorithm is one technique to control the false-positive rate. However, the memory needed by this algorithm rises linearly with the amount of hypothesis tests. Gene-gene interaction studies will require a memory proportional to the squared number of SNPs. A genome-wide epistasis search would therefore require terabytes of memory. Hence, cache problems are likely to occur, increasing the computation time. In this work we present a new version of maxT, requiring an amount of memory independent from the number of genetic effects to be investigated. This algorithm was implemented in C++ in our epistasis screening software MBMDR-3.0.3. We evaluate the new implementation in terms of memory efficiency and speed using simulated data. The software is illustrated on real-life data for Crohn’s disease. Results: In the case of a binary (affected/unaffected) trait, the parallel workflow of MBMDR-3.0.3 analyzes all gene-gene interactions with a dataset of 100,000 SNPs typed on 1000 individuals within 4 days and 9 hours, using 999 permutations of the trait to assess statistical significance, on a cluster composed of 10 blades, containing each four Quad-Core AMD Opteron(tm) Processor 2352 2.1 GHz. In the case of a continuous trait, a similar run takes 9 days. Our program found 14 SNP-SNP interactions with a multiple-testing corrected p-value of less than 0.05 on real-life Crohn’s disease (CD) data. Conclusions: Our software is the first implementation of the MB-MDR methodology able to solve large-scale SNP-SNP interactions problems within a few days, without using much memory, while adequately controlling the type I error rates. A new implementation to reach genome-wide epistasis screening is under construction. In the context of Crohn’s disease, MBMDR-3.0.3 could identify epistasis involving regions that are well known in the field and could be explained from a biological point of view. This demonstrates the power of our software to find relevant phenotype-genotype higher-order associations.

Performance analysis and tuning in multicore environments

Performance analysis is the task of monitor the behavior of a program execution. The main goal is to find out the possible adjustments that might be done in order improve the performance. To be able to get that improvement it is necessary to find the different causes of overhead. Nowadays we are already in the multicore era, but there is a gap between the level of development of the two main divisions of multicore technology (hardware and software). When we talk about multicore we are also speaking of shared memory systems, on this master thesis we talk about the issues involved on the performance analysis and tuning of applications running specifically in a shared Memory system. We move one step ahead to take the performance analysis to another level by analyzing the applications structure and patterns. We also present some tools specifically addressed to the performance analysis of OpenMP multithread application. At the end we present the results of some experiments performed with a set of OpenMP scientific application.

Attenuation of nicotine-induced antinociception, rewarding effects, and dependence in mu-opioid receptor knock-out mice

The involvement of μ-opioid receptors in different behavioral responses elicited by nicotine was explored by using μ-opioid receptor knock-out mice. The acute antinociceptive responses induced by nicotine in the tail-immersion and hot-plate tests were reduced in the mutant mice, whereas no difference between genotypes was observed in the locomotor responses. The rewarding effects induced by nicotine were then investigated using the conditioning place-preference paradigm. Nicotine produced rewarding responses in wild-type mice but failed to produce place preference in knock-out mice, indicating the inability of this drug to induce rewarding effects in the absence of μ-opioid receptors. Finally, the somatic expression of the nicotine withdrawal syndrome, precipitated in dependent mice by the injection of mecamylamine, was evaluated. Nicotine withdrawal was significantly attenuated in knock-out mutants when compared with wild-type mice. In summary, the present results show that μ-opioid receptors are involved in the rewarding responses induced by nicotine and participate in its antinociceptive responses and the expression of nicotine physical dependence.

Desenvolupament d'un sistema de transferència de software per una placa entrenadora

El departament d’electrònica i telecomunicacions de la Universitat de Vic ha dissenyat un conjunt de plaques entrenadores amb finalitat educativa. Perquè els alumnes puguin utilitzar aquestes plaques com a eina d’estudi, és necessari disposar d’un sistema de gravació econòmic i còmode. La major part dels programadors, en aquest cas, no compleixen amb aquests requeriments. L’objectiu d’aquest projecte és dissenyar un sistema de programació que utilitzi la comunicació sèrie i que no requereixi d'un hardware ni software específics. D’aquesta manera, obtenim una placa autònoma i un programador gratuït, de muntatge ràpid i simple d’utilitzar. El sistema de gravació dissenyat s’ha dividit en tres blocs. Per una banda, un programa que anomenem “programador” encarregat de transferir codi de programa des de l’ordinador al microcontrolador de la placa entrenadora. Per altra banda, un programa anomenat “bootloader”, situat al microcontrolador, permet rebre aquest codi de programa i emmagatzemar-lo a les direccions de memòria de programa corresponents. Com a tercer bloc, s’implementa un protocol de comunicació i un sistema de control d’errors per tal d’assegurar una correcta comunicació entre el “programador” i el “bootloader”. Els objectius d’aquest projecte s’han complert i per les proves realitzades, el sistema de programació ha funcionat correctament.

Persistence of cognitive impairment and its negative impact on psychosocial functioning in lithium-treated, euthymic bipolar patients: a 6-year follow-up study.

BACKGROUND: Previous cross-sectional studies report that cognitive impairment is associated with poor psychosocial functioning in euthymic bipolar patients. There is a lack of long-term studies to determine the course of cognitive impairment and its impact on functional outcome. Method A total of 54 subjects were assessed at baseline and 6 years later; 28 had DSM-IV TR bipolar I or II disorder (recruited, at baseline, from a Lithium Clinic Program) and 26 were healthy matched controls. They were all assessed with a cognitive battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory) twice over a 6-year follow-up period. All patients were euthymic (Hamilton Rating Scale for Depression score lower than 8 and Young mania rating scale score lower than 6) for at least 3 months before both evaluations. At the end of follow-up, psychosocial functioning was also evaluated by means of the Functioning Assessment Short Test. RESULTS: Repeated-measures multivariate analysis of covariance showed that there were main effects of group in the executive domain, in the inhibition domain, in the processing speed domain, and in the verbal memory domain (p<0.04). Among the clinical factors, only longer illness duration was significantly related to slow processing (p=0.01), whereas strong relationships were observed between impoverished cognition along time and poorer psychosocial functioning (p<0.05). CONCLUSIONS: Executive functioning, inhibition, processing speed and verbal memory were impaired in euthymic bipolar out-patients. Although cognitive deficits remained stable on average throughout the follow-up, they had enduring negative effects on psychosocial adaptation of patients.

Desenvolupament d'un sistema de transferència de software per una placa entrenadora

El departament d’electrònica i telecomunicacions de la Universitat de Vic ha dissenyat un conjunt de plaques entrenadores amb finalitat educativa. Perquè els alumnes puguin utilitzar aquestes plaques com a eina d’estudi, és necessari disposar d’un sistema de gravació econòmic i còmode. La major part dels programadors, en aquest cas, no compleixen amb aquests requeriments. L’objectiu d’aquest projecte és dissenyar un sistema de programació que utilitzi la comunicació sèrie i que no requereixi d'un hardware ni software específics. D’aquesta manera, obtenim una placa autònoma i un programador gratuït, de muntatge ràpid i simple d’utilitzar. El sistema de gravació dissenyat s’ha dividit en tres blocs. Per una banda, un programa que anomenem “programador” encarregat de transferir codi de programa des de l’ordinador al microcontrolador de la placa entrenadora. Per altra banda, un programa anomenat “bootloader”, situat al microcontrolador, permet rebre aquest codi de programa i emmagatzemar-lo a les direccions de memòria de programa corresponents. Com a tercer bloc, s’implementa un protocol de comunicació i un sistema de control d’errors per tal d’assegurar una correcta comunicació entre el “programador” i el “bootloader”. Els objectius d’aquest projecte s’han complert i per les proves realitzades, el sistema de programació ha funcionat correctament.

Does bounded rationality lead to individual heterogeneity? The impact of the experimentation process and of memory constraints

In this paper we explore the effect of bounded rationality on the convergence of individual behavior toward equilibrium. In the context of a Cournot game with a unique and symmetric Nash equilibrium, firms are modeled as adaptive economic agents through a genetic algorithm. Computational experiments show that (1) there is remarkable heterogeneity across identical but boundedly rational agents; (2) such individual heterogeneity is not simply a consequence of the random elements contained in the genetic algorithm; (3) the more rational agents are in terms of memory abilities and pre-play evaluation of strategies, the less heterogeneous they are in their actions. At the limit case of full rationality, the outcome converges to the standard result of uniform individual behavior.

Aplicació web per a la gestió de nòmines a Andorra

Durant aquesta memòria s'explica d'una forma resumida el treball realitzat per dur a terme una aplicació web comercial per a la realització del càlcul de nòmines al Principat d’Andorra. A l'inici de la memòria es pot llegir una breu introducció sobre el projecte i de mica en mica s'endinsa en l'estudi, anàlisi i disseny del projecte per arribar als objectius establerts. Considero que tant l'anàlisi com el disseny són les parts més importants del projecte perquè un bon treball en aquestes fases pot evitar molts errors a les fases posteriors. Per últim s’explica la situació actual del projecte i es pot llegir una breu conclusió i opinió personal sobre el projecte realitzat.

Studying Avalanches in the ground-state of the two-dimensional random field Ising model driven by an external field

We study the exact ground state of the two-dimensional random-field Ising model as a function of both the external applied field B and the standard deviation ¿ of the Gaussian random-field distribution. The equilibrium evolution of the magnetization consists in a sequence of discrete jumps. These are very similar to the avalanche behavior found in the out-of-equilibrium version of the same model with local relaxation dynamics. We compare the statistical distributions of magnetization jumps and find that both exhibit power-law behavior for the same value of ¿. The corresponding exponents are compared.

Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk

Brain oxidative processes play a major role in age-related cognitive decline, thus consumption of antioxidant-rich foods might help preserve cognition. Our aim was to assess whether consumption of antioxidant-rich foods in the Mediterranean diet relates to cognitive function in the elderly. In asymptomatic subjects at high cardiovascular risk (n = 447; 52% women; age 5580 y) enrolled in the PREDIMED study, a primary prevention dietary-intervention trial, we assessed food intake and cardiovascular risk profile, determined apolipoprotein E genotype, and used neuropsychological tests to evaluate cognitive function.We also measured urinary polyphenols as an objective biomarker of intake. Associations between energy-adjusted food consumption, urinary polyphenols, and cognitive scores were assessed by multiple linear regression models adjusted for potential confounders. Consumption of some foods was independently related to better cognitive function. The specific associations [regression coefficients (95% confidence intervals)] were: total olive oil with immediate verbal memory [0.755 (0.1511.358)]; virgin olive oil and coffee with delayed verbal memory [0.163 (0.0100.316) and 0.294 (0.0550.534), respectively];walnuts with working memory [1.191 (0.0612.322)]; and wine with Mini-Mental State Examination scores [0.252 (0.0060.496)]. Urinary polyphenols were associated with better scores in immediate verbal memory [1.208 (0.2362.180)]. Increased consumption of antioxidant-rich foods in general and of polyphenols in particular is associated with better cognitive performance in elderly subjects at high cardiovascular risk. The results reinforce the notion that Mediterranean diet components might counteract age-related cognitive decline.

Adverse side effects of statins in the oral cavity

Increased plasma levels of cholesterol are high risk factors of cardiovascular disease. Statins are drugs that inhibit cholesterol synthesis at both pancreatic and extrahepathic levels, being the treatment of choice for hypercholesterolemia. Objective: To analyze the side effects of statins in the mouth cavity, and to analyze the symptoms after interruption of the treatment. Design: Observational study, preliminary. Material and methods: Patients aged 50-70, diagnosed with hypercholesterolemia and undergoing treatment with statins, referred from their primary care physician to the dentist"s office. Anamnesis over oral symptoms was performed in the first visit. Statin treatment was discontinued, followed by lab tests and control visits seven and fifteen days later. We monitored the improvement and/or remission of oral symptoms. Statin treatment was resumed, sending out a report of the patient evolution to the PCP. Symptoms were registered in sheet specially designed for the study. Exclusion criteria: patient refusal, use of drugs for dry mouth treatment, Sjögren"s syndrome. Results: n=26 patients. Dry mouth patients: improvement in 17 out of 23 patients (88.5%). Itchiness: 6 out of 15 cases improved (57.7%). Bitterness: improvement in 13 out of 14 patients (53.8%). Cough: improvement in 11 out of 12 patients (46.1%). Discussion: A high percentage of oral symptoms are associated to treatment with statins. There is a marked improvement after temporary interruption of the treatment. Little is known regarding the side effects of oral treatment with statins. This preliminary study includes a relatively small number of patients. The design of experimental treatments will be required to establish a true correlation between statin treatment and oral symptoms

Nicotine-induced antinociception, rewarding effects and physical dependence are decreased in mice lacking the preproenkephalin gene

It has been shown previously that the endogenous opioid system may be involved in the behavioral effects of nicotine. In the present study, the participation of endogenous enkephalins on nicotine responses has been investigated by using preproenkephalin knock-out mice. Acute nicotine-induced hypolocomotion remained unaffected in these mice. In contrast, antinociception elicited in the tail-immersion and hot-plate tests by acute nicotine administration was reduced in mutant animals. The rewarding properties of nicotine were then investigated using the place-conditioning paradigm. Nicotine induced a conditioned place preference in wild-type animals, but this effect was absent in knock-out mice. Accordingly, in vivo microdialysis studies revealed that the enhancement in dopamine extracellular levels in the nucleus accumbens induced by nicotine was also reduced in preproenkephalin-deficient mice. Finally, the somatic expression of the nicotine withdrawal syndrome precipitated in nicotine-dependent mice by mecamylamine was significantly attenuated in mutant animals. In summary, the present results indicate that endogenous opioid peptides derived from preproenkephalin are involved in the antinociceptive and rewarding properties of nicotine and participate in the expression of physical nicotine dependence.

Dendrochronological study of the avalanche path Canal del Roc Roig: first results of the ALUDEX Project in the Pyrenees

Historical data about ancient avalanches are scarce in the Pyrenees. Dendrochronology can provide new data about past avalanches and their return period, but up to now little research has been carried out with this purpose. The Aludex project aims to obtain information about the frequency and extent of extreme avalanches, using a dendrochronological and a nivo-meteorological approach. In this paper, we present the results of a dendrochronological study of the Canal del Roc Roig avalanche path which was affected by two extreme avalanches in February 1996. This first dendrochronological study has permitted us to assess the tree-ring signals due to avalanche events in 53 out of 132 dated trees. The trees presented a variety of responses to the 1996 avalanche events. It is shown that the type of tree-ring signal depends on tree age. The methodology has proved successful in detecting the 1996 and 1972 documented avalanche events, and provided outstanding evidence of undocumented past events such as one in 1930.

Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk

Brain oxidative processes play a major role in age-related cognitive decline, thus consumption of antioxidant-rich foods might help preserve cognition. Our aim was to assess whether consumption of antioxidant-rich foods in the Mediterranean diet relates to cognitive function in the elderly. In asymptomatic subjects at high cardiovascular risk (n = 447; 52% women; age 55-80 y) enrolled in the PREDIMED study, a primary prevention dietary-intervention trial, we assessed food intake and cardiovascular risk profile, determined apolipoprotein E genotype, and used neuropsychological tests to evaluate cognitive function.We also measured urinary polyphenols as an objective biomarker of intake. Associations between energy-adjusted food consumption, urinary polyphenols, and cognitive scores were assessed by multiple linear regression models adjusted for potential confounders. Consumption of some foods was independently related to better cognitive function. The specific associations [regression coefficients (95% confidence intervals)] were: total olive oil with immediate verbal memory [0.755 (0.151-1.358)]; virgin olive oil and coffee with delayed verbal memory [0.163 (0.010-0.316) and 0.294 (0.055-0.534), respectively];walnuts with working memory [1.191 (0.061-2.322)]; and wine with Mini-Mental State Examination scores [0.252 (0.006-0.496)]. Urinary polyphenols were associated with better scores in immediate verbal memory [1.208 (0.236-2.180)]. Increased consumption of antioxidant-rich foods in general and of polyphenols in particular is associated with better cognitive performance in elderly subjects at high cardiovascular risk. The results reinforce the notion that Mediterranean diet components might counteract age-related cognitive decline.

Bystander responses to a violent incident in an immersive virtual environment

Under what conditions will a bystander intervene to try to stop a violent attack by one person on another? It is generally believed that the greater the size of the crowd of bystanders, the less the chance that any of them will intervene. A complementary model is that social identity is critical as an explanatory variable. For example, when the bystander shares common social identity with the victim the probability of intervention is enhanced, other things being equal. However, it is generally not possible to study such hypotheses experimentally for practical and ethical reasons. Here we show that an experiment that depicts a violent incident at life-size in immersive virtual reality lends support to the social identity explanation. 40 male supporters of Arsenal Football Club in England were recruited for a two-factor between-groups experiment: the victim was either an Arsenal supporter or not (in-group/out-group), and looked towards the participant for help or not during the confrontation. The response variables were the numbers of verbal and physical interventions by the participant during the violent argument. The number of physical interventions had a significantly greater mean in the ingroup condition compared to the out-group. The more that participants perceived that the Victim was looking to them for help the greater the number of interventions in the in-group but not in the out-group. These results are supported by standard statistical analysis of variance, with more detailed findings obtained by a symbolic regression procedure based on genetic programming. Verbal interventions made during their experience, and analysis of post-experiment interview data suggest that in-group members were more prone to confrontational intervention compared to the out-group who were more prone to make statements to try to diffuse the situation.