Interactions between uncoupling protein 2 gene polymorphisms, obesity and alcohol intake on liver function: a large meta-analysed population-based study

BACKGROUND AND OBJECTIVE: Given the role of uncoupling protein 2 (UCP2) in the accumulation of fat in the hepatocytes and in the enhancement of protective mechanisms in acute ethanol intake, we hypothesised that UCP2 polymorphisms are likely to cause liver disease through their interactions with obesity and alcohol intake. To test this hypothesis, we investigated the interaction between tagging polymorphisms in the UCP2 gene (rs2306819, rs599277 and rs659366), alcohol intake and obesity traits such as BMI and waist circumference (WC) on alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) in a large meta-analysis of data sets from three populations (n=20 242). DESIGN AND METHODS: The study populations included the Northern Finland Birth Cohort 1966 (n=4996), Netherlands Study of Depression and Anxiety (n=1883) and LifeLines Cohort Study (n=13 363). Interactions between the polymorphisms and obesity and alcohol intake on dichotomised ALT and GGT levels were assessed using logistic regression and the likelihood ratio test. RESULTS: In the meta-analysis of the three cohorts, none of the three UCP2 polymorphisms were associated with GGT or ALT levels. There was no evidence for interaction between the polymorphisms and alcohol intake on GGT and ALT levels. In contrast, the association of WC and BMI with GGT levels varied by rs659366 genotype (Pinteraction=0.03 and 0.007, respectively; adjusted for age, gender, high alcohol intake, diabetes, hypertension and serum lipid concentrations). CONCLUSION: In conclusion, our findings in 20 242 individuals suggest that UCP2 gene polymorphisms may cause liver dysfunction through the interaction with body fat rather than alcohol intake.

Classificação de padrões através de um comitê de máquinas aprimorado por aprendizagem por reforço

Reinforcement learning is a machine learning technique that, although finding a large number of applications, maybe is yet to reach its full potential. One of the inadequately tested possibilities is the use of reinforcement learning in combination with other methods for the solution of pattern classification problems. It is well documented in the literature the problems that support vector machine ensembles face in terms of generalization capacity. Algorithms such as Adaboost do not deal appropriately with the imbalances that arise in those situations. Several alternatives have been proposed, with varying degrees of success. This dissertation presents a new approach to building committees of support vector machines. The presented algorithm combines Adaboost algorithm with a layer of reinforcement learning to adjust committee parameters in order to avoid that imbalances on the committee components affect the generalization performance of the final hypothesis. Comparisons were made with ensembles using and not using the reinforcement learning layer, testing benchmark data sets widely known in area of pattern classification

The Genome Sequence of Taurine Cattle: A Window to Ruminant Biology and Evolution

To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.

Power-law distributions for the citation index of scientific publications and scientists

The number of citations of a scientific publication or of an individual scientist has become an important factor of quality assessment in science. We report a study of the statistical distribution of the citation index of both scientific publications and scientists. We give numerical evidence that Tsallis (power law) statistics explains the entire distribution over eight orders of magnitude (10-4 to 10(4)). Also, we draw Zipf plots in order to analyze the statistical distribution of the citation index of Brazilian and international physicists and chemists. The relatively small group of Brazilian scientists seems more adequate to explain the dynamics of the citation index. In this case, we find that the distribution of the citation index can also be explained by a gradually truncated power law with similar parameters. We finally discuss possible mechanisms behind the citation index of scientists and scientific publications.

Gradually truncated log-normal in USA publicly traded firm size distribution

We study the statistical distribution of firm size for USA and Brazilian publicly traded firms through the Zipf plot technique. Sale size is used to measure firm size. The Brazilian firm size distribution is given by a log-normal distribution without any adjustable parameter. However, we also need to consider different parameters of log-normal distribution for the largest firms in the distribution, which are mostly foreign firms. The log-normal distribution has to be gradually truncated after a certain critical value for USA firms. Therefore, the original hypothesis of proportional effect proposed by Gibrat is valid with some modification for very large firms. We also consider the possible mechanisms behind this distribution. (c) 2006 Published by Elsevier B.V.

Size limiting in Tsallis statistics

Power law scaling is observed in many physical, biological and socio-economical complex systems and is now considered an important property of these systems. In general, power law exists in the central part of the distribution. It has deviations from power law for very small and very large variable sizes. Tsallis, through non-extensive thermodynamics, explained power law distribution in many cases including deviation from the power law. In case of very large steps, the used the heuristic crossover approach. In the present we present an alternative model in which we consider that the entropy factor 9 decreases with variable size due to the softening of long range interactions or memory. We apply this model for distribution of citation index of scientists and examination scores and are able to explain the distribution for entire variable range. In the present model, we can have very sharp cut-off without interfering with power law in its central part as observed in many cases. (C) 2008 Elsevier B.V. All rights reserved.

The gradually truncated Lévy flight: Stochastic process for complex systems

Power-law distributions, i.e. Levy flights have been observed in various economical, biological, and physical systems in high-frequency regime. These distributions can be successfully explained via gradually truncated Levy flight (GTLF). In general, these systems converge to a Gaussian distribution in the low-frequency regime. In the present work, we develop a model for the physical basis for the cut-off length in GTLF and its variation with respect to the time interval between successive observations. We observe that GTLF automatically approach a Gaussian distribution in the low-frequency regime. We applied the present method to analyze time series in some physical and financial systems. The agreement between the experimental results and theoretical curves is excellent. The present method can be applied to analyze time series in a variety of fields, which in turn provide a basis for the development of further microscopic models for the system. © 2000 Elsevier Science B.V. All rights reserved.

Power law distribution in education: University entrance examination

We studied the statistical distribution of candidate's performance which is measured through their marks in university entrance examination (Vestibular) of UNESP (Universidade Estadual Paulista) for years 1998, 1999, and 2000. All students are divided in three groups: Physical, Biological and Humanities. We paid special attention to the examination of Portuguese language which is common for all and examinations for the particular area. We observed long ubiquitous power law tails in Physical and Biological sciences. This indicate the presence of strong positive feedback in sciences. We are able to explain completely these statistical distributions through Gradually Truncated Power law distributions which we developed recently to explain statistical behavior of financial market. The statistical distribution in case of Portuguese language and humanities is close to normal distribution. We discuss the possible reason for this peculiar behavior.

Effect of acute and chronic GVHD on relapse and survival after reduced-intensity conditioning allogeneic transplantation for myeloma

We evaluated the effect of acute and chronic GVHD on relapse and survival after allogeneic hematopoietic SCT (HSCT) for multiple myeloma using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC). The outcomes of 177 HLA-identical sibling HSCT recipients between 1997 and 2005, following NMA (n = 98) or RIC (n = 79) were analyzed. In 105 patients, autografting was followed by planned NMA/RIC allogeneic transplantation. The impact of GVHD was assessed as a time-dependent covariate using Cox models. The incidence of acute GVHD (aGVHD; grades I-IV) was 42% (95% confidence interval (CI), 35-49%) and of chronic GVHD (cGVHD) at 5 years was 59% (95% CI, 49-69%), with 70% developing extensive cGVHD. In multivariate analysis, aGVHD (>= grade I) was associated with an increased risk of TRM (relative risk (RR) = 2.42, P = 0.016), whereas limited cGVHD significantly decreased the risk of myeloma relapse (RR = 0.35, P = 0.035) and was associated with superior EFS (RR = 0.40, P = 0.027). aGVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR = 3.52, P = 0.001). The reduction in relapse risk associated with cGVHD is consistent with a beneficial graft-vs-myeloma effect, but this did not translate into a survival advantage. Bone Marrow Transplantation (2012) 47, 831-837; doi:10.1038/bmt.2011.192; published online 26 September 2011

Change over time in posttraumatic stress caused by myocardial infarction and predicting variables

The traumatic experience of a heart attack may evolve into symptoms of posttraumatic stress disorder, which can be diagnosed at the earliest 1 month after myocardial infarction (MI). While several predictors of posttraumatic stress in the first year after MI have been described, we particularly sought to identify longer-term predictors and predictors of change in posttraumatic stress over time.

Structure-activity relationship and mechanism of action studies of manzamine analogues for the control of neuroinflammation and cerebral infections

Structure-activity relationship studies were carried out by chemical modification of manzamine A (1), 8-hydroxymanzamine A (2), manzamine F (14), and ircinal isolated from the sponge Acanthostrongylophora. The derived analogues were evaluated for antimalarial, antimicrobial, and antineuroinflammatory activities. Several modified products exhibited potent and improved in vitro antineuroinflammatory, antimicrobial, and antimalarial activity. 1 showed improved activity against malaria compared to chloroquine in both multi- and single-dose in vivo experiments. The significant antimalarial potential was revealed by a 100% cure rate of malaria in mice with one administration of 100 mg/kg of 1. The potent antineuroinflammatory activity of the manzamines will provide great benefit for the prevention and treatment of cerebral infections (e.g., Cryptococcus and Plasmodium). In addition, 1 was shown to permeate across the blood-brain barrier (BBB) in an in vitro model using a MDR-MDCK monolayer. Docking studies support that 2 binds to the ATP-noncompetitive pocket of glycogen synthesis kinase-3beta (GSK-3beta), which is a putative target of manzamines. On the basis of the results presented here, it will be possible to initiate rational drug design efforts around this natural product scaffold for the treatment of several different diseases.

Distress related to myocardial infarction and cardiovascular outcome: a retrospective observational study

Background During acute coronary syndromes patients perceive intense distress. We hypothesized that retrospective ratings of patients' MI-related fear of dying, helplessness, or pain, all assessed within the first year post-MI, are associated with poor cardiovascular outcome. Methods We studied 304 patients (61 ± 11 years, 85% men) who after a median of 52 days (range 12-365 days) after index MI retrospectively rated the level of distress in the form of fear of dying, helplessness, or pain they had perceived at the time of MI on a numeric scale ranging from 0 ("no distress") to 10 ("extreme distress"). Non-fatal hospital readmissions due to cardiovascular disease (CVD) related events (i.e., recurrent MI, elective and non-elective stent implantation, bypass surgery, pacemaker implantation, cerebrovascular incidents) were assessed at follow-up. The relative CVD event risk was computed for a (clinically meaningful) 2-point increase of distress using Cox proportional hazard models. Results During a median follow-up of 32 months (range 16-45), 45 patients (14.8%) experienced a CVD-related event requiring hospital readmission. Greater fear of dying (HR 1.21, 95% CI 1.03-1.43), helplessness (HR 1.22, 95% CI 1.04-1.44), or pain (HR 1.27, 95% CI 1.02-1.58) were significantly associated with an increased CVD risk without adjustment for covariates. A similarly increased relative risk emerged in patients with an unscheduled CVD-related hospital readmission, i.e., when excluding patients with elective stenting (fear of dying: HR 1.26, 95% CI 1.05-1.51; helplessness: 1.26, 95% CI 1.05-1.52; pain: HR 1.30, 95% CI 1.01-1.66). In the fully-adjusted models controlling for age, the number of diseased coronary vessels, hypertension, and smoking, HRs were 1.24 (95% CI 1.04-1.46) for fear of dying, 1.26 (95% CI 1.06-1.50) for helplessness, and 1.26 (95% CI 1.01-1.57) for pain. Conclusions Retrospectively perceived MI-related distress in the form of fear of dying, helplessness, or pain was associated with non-fatal cardiovascular outcome independent of other important prognostic factors.

Non-fatal cardiovascular outcome in patients with posttraumatic stress symptoms caused by myocardial infarction

Objectives Posttraumatic stress disorder (PTSD) prospectively increases the risk of incident cardiovascular disease (CVD) independent of other risk factors in otherwise healthy individuals. Between 10% and 20% of patients develop PTSD related to the traumatic experience of myocardial infarction (MI). We investigated the hypothesis that PTSD symptoms caused by MI predict adverse cardiovascular outcome. Methods We studied 297 patients (61 ± 10 years, 83% men) who self-rated PTSD symptoms attributable to a previous index MI. Non-fatal CVD-related hospital readmissions (i.e. recurrent MI, elective and non-elective intracoronary stenting, bypass surgery, pacemaker implantation, cardiac arrhythmia, cerebrovascular event) were assessed at follow-up. Cox proportional hazard models controlled for demographic factors, coronary heart disease severity, major CVD risk factors, cardiac medication, and mental health treatment. Results Forty-three patients (14.5%) experienced an adverse event during a mean follow-up of 2.8 years (range 1.3–3.8). A 10 point higher level in the PTSD symptom score (mean 8.8 ± 9.0, range 0–47) revealed a hazard ratio (HR) of 1.42 (95% CI 1.07–1.88) for a CVD-related hospital readmission in the fully adjusted model. A similarly increased risk (HR 1.45, 95% CI 1.07–1.97) emerged for patients with a major or unscheduled CVD-related readmission (i.e. when excluding patients with elective stenting). Conclusions Elevated levels of PTSD symptoms caused by MI may adversely impact non-fatal cardiovascular outcome in post-MI patients independent of other important prognostic factors. The possible importance of PTSD symptoms as a novel prognostic psychosocial risk factor in post-MI patients warrants further study.