Population and Computational Analysis of the MGEA6 P521A Variation as a Risk Factor for Familial Idiopathic Basal Ganglia Calcification (Fahr`s Disease)

Familial idiopathic basal ganglia calcification, also known as ""Fahr`s disease"" (FD), is a neuropsychiatric disorder with autosomal dominant pattern of inheritance and characterized by symmetric basal ganglia calcifications and, occasionally, other brain regions. Currently, there are three loci linked to this devastating disease. The first one (IBGC1) is located in 14q11.2-21.3 and the other two have been identified in 2q37 (IBGC2) and 8p21.1-q11.13 (IBGC3). Further studies identified a heterozygous variation (rs36060072) which consists in the change of the cytosine to guanine located at MGEA6/CTAGE5 gene, present in all of the affected large American family linked to IBGC1. This missense substitution, which induces changes of a proline to alanine at the 521 position (P521A), in a proline-rich and highly conserved protein domain was considered a rare variation, with a minor allele frequency (MAF) of 0.0058 at the US population. Considering that the population frequency of a given variation is an indirect indicative of potential pathogenicity, we screened 200 chromosomes in a random control set of Brazilian samples and in two nuclear families, comparing with our previous analysis in a US population. In addition, we accomplished analyses through bioinformatics programs to predict the pathogenicity of such variation. Our genetic screen found no P521A carriers. Polling these data together with the previous study in the USA, we have now a MAF of 0.0036, showing that this mutation is very rare. On the other hand, the bioinformatics analysis provided conflicting findings. There are currently various candidate genes and loci that could be involved with the underlying molecular basis of FD etiology, and other groups suggested the possible role played by genes in 2q37, related to calcium metabolism, and at chromosome 8 (NRG1 and SNTG1). Additional mutagenesis and in vivo studies are necessary to confirm the pathogenicity for variation in the P521A MGEA6.

Analysis and risk estimates to workers of Brazilian granitic industries and sandblasters exposed to respirable crystalline silica and natural radionuclides

Occupational exposure to respirable crystalline silica and to radiation emitted by natural radionuclides present both in rocks and sands was studied in the Brazilian extractive process and granite product manufacture. Respirable airborne dust samples were collected in working environments, where workers perform different tasks with distinct commercial granites types, and also in places where sandblasters work with sands from different origins. The free crystalline silica contents were determined using X-ray diffraction of the respirable particulate fraction of each sample. Dust samples from granite cutting and sandblasting ambient had the natural radionuclides concentrations measured by gamma spectrometry. Dust concentrations in the workplaces were quite variable, reaching values up to 10 times higher than the respirable particle mass threshold limit value (TLV) set by the American Conference for Governmental Industrial Hygienists of 3 mg m(-3). Also the free crystalline silica concentrations were high. reaching values up to 48 times the TLV of 0.025 mg m(-3). Additionally, our results suggest that the risk of radiation-induced cancer in the granite or marble industries is negligible. However, the combined exposure to dust, gamma radiation, and radon daughter products could result in the enhancement of lung cancer risks associated to sandblasting activities. (C) 2010 Elsevier Ltd. All rights reserved.

Social welfare analysis in a simple financial economy with risk regulation

In the last years, regulating agencies of rnany countries in the world, following recommendations of the Basel Committee, have compelled financiaI institutions to maintain minimum capital requirements to cover market risk. This paper investigates the consequences of such kind of regulation to social welfare and soundness of financiaI institutions through an equilibrium model. We show that the optimum level of regulation for each financiaI institution (the level that maximizes its utility) depends on its appetite for risk and some of them can perform better in a regulated economy. In addition, another important result asserts that under certain market conditions the financiaI fragility of an institution can be greater in a regulated econolny than in an unregulated one

Funding social sector activity in Brazil: a case study analysis of agency risk incidence and mitigation

Empresas e organizações sociais têm um papel cada vez mais importante no mercado brasileiro. Essas organizações - sejam elas com ou sem fins lucrativos –têm como objetivocausar um profundo e positivo impacto social.Ambas enfrentamtambém o mesmo desafio: financiar as suas operações. Recentemente, dois modelos inovadores de financiamento, o fundo de venture capitalVox Capital e o fundo de empréstimo social SITAWI, entraram no mercado brasileiro para solucionar esse desafio. Este estudo analisa ambos os fundos,associando o problema do financiamento de empresas e organizações sociais às teorias tradicionais de negócio. Mais especificamente, por meio de um estudo de caso,é avaliado se o risco de agência (agency risk) explica as práticas e o designcontratual utilizados pelos fundos. A pesquisa é baseada num estudo de Alemany e Scarlata (2010) sobre a estruturação dos negócios de fundos filantrópicos de capital empreendedor (PhVC, na sigla em inglês) na América do Norte e na Europa. Uma definição chave desse estudo é que organizações sem fins lucrativos, ao contrário daquelas com fins lucrativos, estão sujeitas a uma restrição de distribuição de lucros. Embora Alemany e Scarlata (2010) tivessem descobertoque parceria (stewardship), mais do que o problema de agência (agency problem), explica a estrutura dos negócios dos fundos PhVC, as implicações do presente estudo de caso para o Brasil são diferentes. Os resultados sugerem que o problema de agência,mais do que a parceria,descreve adequadamente os contratos analisados de financiamento. Detectou-seque cláusulas contratuais não foram apenas usadas para mitigar o risco de agênciaresultanteda ausência de uma restrição de distribuição de lucros, mas também para reger as estruturas cooperativas com organizações sem fins lucrativos. No caso de SITAWI, a restrição dos destinatários de fundos de distribuir lucros provou-se uma ferramenta efetiva para alinhar os interesses entre os financiadores e os destinatários dos fundos. Apesar daimplicação da presença de parceria, os contratos do fundo social contiveram cláusulas geralmente usadas para reduzir o risco de agência. No caso de Vox Capital, os destinatários dos fundos eram empresas com fins lucrativos, portanto não sujeitas à restrição de distribuição de lucros. O modelo de negócio de Vox Capital é organizado para impedir qualquer incidência potencial do problema de agência. Ambos os fundos, independentemente da estrutura jurídica dos beneficiários destes fundos, evidenciaram o intuito de garantir a aplicação de práticas de negócio utilizadas pelas empresas tradicionais do setor corporativo em vez daquelas utilizadas no setor social.

We're Chained: an analysis of systemic risk in finance

This dissertation presents two papers on how to deal with simple systemic risk measures to assess portfolio risk characteristics. The first paper deals with the Granger-causation of systemic risk indicators based in correlation matrices in stock returns. Special focus is devoted to the Eigenvalue Entropy as some previous literature indicated strong re- sults, but not considering different macroeconomic scenarios; the Index Cohesion Force and the Absorption Ratio are also considered. Considering the S&P500, there is not ev- idence of Granger-causation from Eigenvalue Entropies and the Index Cohesion Force. The Absorption Ratio Granger-caused both the S&P500 and the VIX index, being the only simple measure that passed this test. The second paper develops this measure to capture the regimes underlying the American stock market. New indicators are built using filtering and random matrix theory. The returns of the S&P500 is modelled as a mixture of normal distributions. The activation of each normal distribution is governed by a Markov chain with the transition probabilities being a function of the indicators. The model shows that using a Herfindahl-Hirschman Index of the normalized eigenval- ues exhibits best fit to the returns from 1998-2013.

Convergence analysis of sampling-based decomposition methods for risk-averse multistage stochastic convex programs

We consider a class of sampling-based decomposition methods to solve risk-averse multistage stochastic convex programs. We prove a formula for the computation of the cuts necessary to build the outer linearizations of the recourse functions. This formula can be used to obtain an efficient implementation of Stochastic Dual Dynamic Programming applied to convex nonlinear problems. We prove the almost sure convergence of these decomposition methods when the relatively complete recourse assumption holds. We also prove the almost sure convergence of these algorithms when applied to risk-averse multistage stochastic linear programs that do not satisfy the relatively complete recourse assumption. The analysis is first done assuming the underlying stochastic process is interstage independent and discrete, with a finite set of possible realizations at each stage. We then indicate two ways of extending the methods and convergence analysis to the case when the process is interstage dependent.

A Meta-Analysis of Predation Risk Effects on Pollinator Behaviour

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Analysis of the risk factors related to the immune humoral anti-Anaplasma marginale in dairy cattle

Anaplasma marginale is the most prevalent pathogen of cattle transmitted by ticks in the world. This study aimed to evaluate the risk factors for anaplasmosis in dairy cattle. Fifty dairy cattle from the herd of Empresa de Pesquisa Agropecuaria do Estado do Rio de Janeiro were selected by proportional stratified sampling. The risk factors evaluated were: physiological state, race pattern, number of lactations, milk production, infestation by Rhipicephalus microplus and animal density. Antibody activity against A. marginale was determined using the indirect enzyme-linked immunosorbent assay. The percentual values of seroprevalence for A. marginale were submitted to X2 test, and the level of minimum significance, to keep a factor in the model of logistic regression, was fixated in 5%. It was observed that pregnancy and lactation influenced significantly (p<0.05) in the seropositivity of the animals. Bos indicus animals had 5.21 times more chances of being seropositive than B. taurus animals. Primiparous female had 88% more chances of being seropositive than pluriparous female. Animals with high milk production were 63% more positive than low production animals. When infested by ticks the animals had 39% more chance of being seropositive to A. marginale. Bos indicus animals presented 5.21 times more chance of being seropositive than B. taurus animals. Primiparous females presented 88% more chance of being seropositive than the pluriparous ones. High milk production animals were 63% more positive than the low production ones. When infested by ticks the animals had 39% more chance of being seropositive to A. marginale. High density grazing provided for the animals 3.2 times more chances of being seropositive than low density ones. The herd was classified as erratic to A. marginale, even being placed in a steady enzootic area.

Prevalence of cardiovascular risk factors among Latin American adolescents: a multilevel analysis

High blood pressure (HBP) and obesity is a well-established major risk factor for stroke and coronary heart disease. However, the literatures are scarce about these informations in adolescents from low-and-middle income countries. This school-based survey was carried out among students from Maringá (Brazil) and Buenos Aires (Argentina) selected random sampling. We studied 991 Brazilian adolescents (54.5% girls) in the age range of 14-18 years. In Argentina, we studied 933 adolescents (45.9% female) in the age range of 11-17 years. The outcomes of this study are general obesity, abdominal obesity and HBP. The associated factors analysed were gender, age and health behaviours. The prevalence of obesity was 5.8% in Brazil and 2.8% in Argentina, the prevalence of abdominal obesity was 32.7% in Brazil and 11.1% in Argentina, the prevalence of HBP was 14.9% in Brazil and 13.5% in Argentina. The multilevel analysis showed that older adolescents (>14 years old) have a little likelihood of being overweight, whereas male adolescents are more likely to be obese and have HBP. The abdominal obesity in both indicators were not associated with the independent variables. The prevalence of cardiovascular risk factors is high in Latin American adolescents independent of each country, and was associated with male gender.Journal of Human Hypertension advance online publication, 15 August 2013; doi:10.1038/jhh.2013.74.

Analysis of the risk factors relating to cows' resistance to Rhipicephalus microplus ticks during the peripartum

This study aimed to evaluate season, breed, number of lactations and milk production as risk factors relating to Rhipicephalus microplus infestation in dairy cows during the peripartum. Eighty-four animals were randomly selected through proportional stratified sampling. All engorged and partially engorged female R. microplus specimens measuring 4.5-8.0 mm were counted during the 5 weeks before calving, calving week and 5 weeks after calving. The peripartum had a significant effect [calving (p < 0.05; prevalence ratio (PR)= 3.12) and post calving (p < 0.05; PR = 2.02)] on R. microplus infestation. Although the average tick count was higher during the rainy season than during the dry season, there was no significant difference (p = 0.055; PR = 0.63). The average R. microplus count was significantly higher (p < 0.05; PR = 2.10) in Bos taurus animals, followed by F1 (p < 0.05; PR = 1.64) and Girolando (p < 0.05; PR = 1.39). The average R. microplus count was significantly higher (p < 0.05; PR = 0.97) in first-lactation animals, followed by those at the second, third and, fourth or subsequent lactation. Milk production showed a negative correlation with R. microplus count, such that high-production animals were significantly (p = 0.003; PR = 2.04) more vulnerable to infestation than were low-production animals. First-lactation and high-production B. taurus animals had greatest vulnerability to R. microplus infestation over the peripartum period, and constituted the at-risk group in the dairy herd.u

Application of discriminant analysis-based model for prediction of risk of low back disorders due to workplace design in industrial jobs

The occupational exposure limits of different risk factors for development of low back disorders (LBDs) have not yet been established. One of the main problems in setting such guidelines is the limited understanding of how different risk factors for LBDs interact in causing injury, since the nature and mechanism of these disorders are relatively unknown phenomena. Industrial ergonomists' role becomes further complicated because the potential risk factors that may contribute towards the onset of LBDs interact in a complex manner, which makes it difficult to discriminate in detail among the jobs that place workers at high or low risk of LBDs. The purpose of this paper was to develop a comparative study between predictions based on the neural network-based model proposed by Zurada, Karwowski & Marras (1997) and a linear discriminant analysis model, for making predictions about industrial jobs according to their potential risk of low back disorders due to workplace design. The results obtained through applying the discriminant analysis-based model proved that it is as effective as the neural network-based model. Moreover, the discriminant analysis-based model proved to be more advantageous regarding cost and time savings for future data gathering.

Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium

To investigate the potential role of vitamin or mineral supplementation on the risk of head and neck cancer (HNC), we analyzed individual-level pooled data from 12 casecontrol studies (7,002 HNC cases and 8,383 controls) participating in the International Head and Neck Cancer Epidemiology consortium. There were a total of 2,028 oral cavity cancer, 2,465 pharyngeal cancer, 874 unspecified oral/pharynx cancer, 1,329 laryngeal cancer and 306 overlapping HNC cases. Odds ratios (OR) and 95% confidence intervals (CIs) for self reported ever use of any vitamins, multivitamins, vitamin A, vitamin C, vitamin E, and calcium, beta-carotene, iron, selenium and zinc supplements were assessed. We further examined frequency, duration and cumulative exposure of each vitamin or mineral when possible and stratified by smoking and drinking status. All ORs were adjusted for age, sex, race/ethnicity, study center, education level, pack-years of smoking, frequency of alcohol drinking and fruit/vegetable intake. A decreased risk of HNC was observed with ever use of vitamin C (OR = 0.76, 95% CI = 0.590.96) and with ever use of calcium supplement (OR = 0.64, 95% CI = 0.420.97). The inverse association with HNC risk was also observed for 10 or more years of vitamin C use (OR = 0.72, 95% CI = 0.540.97) and more than 365 tablets of cumulative calcium intake (OR = 0.36, 95% CI = 0.160.83), but linear trends were not observed for the frequency or duration of any supplement intake. We did not observe any strong associations between vitamin or mineral supplement intake and the risk of HNC.

Risk Factor Analysis of Late Survival After Heart Transplantation According to Donor Profile: A Multi-Institutional Retrospective Study of 512 Transplants

Introduction. Patients with terminal heart failure have increased more than the available organs leading to a high mortality rate on the waiting list. Use of Marginal and expanded criteria donors has increased due to the heart shortage. Objective. We analyzed all heart transplantations (HTx) in Sao Paulo state over 8 years for donor profile and recipient risk factors. Method. This multi-institutional review collected HTx data from all institutions in the state of Sao Paulo, Brazil. From 2002 to 2008 (6 years), only 512 (28.8%) of 1777 available heart donors were accepted for transplantation. All medical records were analyzed retrospectively; none of the used donors was excluded, even those considered to be nonstandard. Results. The hospital mortality rate was 27.9% (n = 143) and the average follow-up time was 29.4 +/- 28.4 months. The survival rate was 55.5% (n = 285) at 6 years after HTx. Univariate analysis showed the following factors to impact survival: age (P = .0004), arterial hypertension (P = .4620), norepinephrine (P = .0450), cardiac arrest (P = .8500), diabetes mellitus (P = .5120), infection (P = .1470), CKMB (creatine kinase MB) (P = .8694), creatinine (P = .7225), and Na+ (P = .3273). On multivariate analysis, only age showed significance; logistic regression showed a significant cut-off at 40 years: organs from donors older than 40 years showed a lower late survival rates (P = .0032). Conclusions. Donor age older than 40 years represents an important risk factor for survival after HTx. Neither donor gender nor norepinephrine use negatively affected early survival.

Work Precariousness and Risk of Accidents in Civil Construction: A study based on the Collective Work Analysis

This paper aims to describe the construction workers' activities, as well as their perceptions about risks and workload. The study, based on the Collective Work Analysis, is part of a broader public policies project for the improvement of SIVAT (Surveillance System of Work Accidents) - in the city of Piracicaba (Southeastern Brazil). Civil construction was prioritized given the epidemiological magnitude of the occurrence of work accidents and the limited efficacy of traditional surveillance initiatives in this sector due to informal employment practices, outsourcing, high staff turnover, etc. The workers have a high level of awareness concerning the risk of accidents, but they believe that the main preventive measures hinder or even make it impossible for them to carry out the tasks. Our findings question the efficacy of traditional training for adherence to safety practices, thus highlighting the need for a transformative pedagogy for preventive practices and the health promotion of workers.