A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Association of SNPs on CAPN1 and CAST genes with tenderness in Nellore cattle

We examined whether single-nucleotide polymorphisms (SNPs) in the calpain (CAPN) and calpastatin (CAST) genes, described from Bos primigenius taurus, are polymorphic in Nellore cattle. We also looked for a possible association of linkage disequilibrium of this polymorphism with tenderness of the longissimus dorsi muscle after 7, 14 and 21 days of postmortem aging in 638 purebred Nellore bulls. Meat tenderness was measured as Warner-Bratzler shear force. Additive and dominance effects were tested for SNPs of the three genotypic classes; the substitution effect was tested for SNPs with missing genotypic classes. Genotypic and gene frequencies were also calculated for the different SNPs. An increase in tenderness was observed from 7 to 21 days; the average values for shear force at 7, 14 and 21 days of aging were 5.92 +/- 0.06, 4.92 +/- 0.05, and 4.38 +/- 0.04 kg, respectively. All markers showed polymorphism, but there was no CC genotype for CAPN316, and few animals showed the AA genotype for CAPN530. The alleles CAPN4751, UOGCAST1, and WSUCAST were found to have additive and dominance effects for shear force at 7, 14 and 21 days, while CAPN316 showed a substitution effect for shear force at 7 and 21 days. An additive-by-additive epistatic interaction was observed between CAPN4751 and markers on the CAST gene. In conclusion, these markers should be considered for use in breeding programs.

Association of Trypanosoma vivax in extracellular sites with central nervous system lesions and changes in cerebrospinal fluid in experimentally infected goats

Changes in cerebrospinal fluid (CSF) and anatomical and histopathological central nervous system (CNS) lesions were evaluated, and the presence of Trypanosoma vivax in CNS tissues was investigated through PCR. Twelve adult male goats were divided into three groups (G): G1, infected with T. vivax and evaluated during the acute phase; G2, infected goats evaluated during the chronic phase; and G3, consisting of non-infected goats. Each goat from G1 and G2 was infected with 1.25 x 10(5) trypomastigotes. Cerebrospinal fluid (CSF) analysis and investigation of T. vivax was performed at the 15(th) day post-infection (dpi) in G1 goats and on the fifth day after the manifestation of nervous system infection signs in G2 goats. All goats were necropsied, and CNS fragments from G1 and G2 goats were evaluated by PCR for the determination of T. vivax. Hyperthermia, anemia and parasitemia were observed from the fifth dpi for G1 and G2, with the highest parasitemia peak between the seventh and 21(st) dpi. Nervous system infection signs were observed in three G2 goats between the 30(th) and 35(th) dpi. CSF analysis revealed the presence of T. vivax for G2. Meningitis and meningoencephalitis were diagnosed in G2. PCR were positive for T. vivax in all the samples tested. In conclusion, T. vivax may reach the nervous tissue resulting in immune response from the host, which is the cause of progressive clinical and pathological manifestations of the CNS in experimentally infected goats.

Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies

Background: The ideal malaria parasite populations for initial mapping of genomic regions contributing to phenotypes such as drug resistance and virulence, through genome-wide association studies, are those with high genetic diversity, allowing for numerous informative markers, and rare meiotic recombination, allowing for strong linkage disequilibrium (LD) between markers and phenotype-determining loci. However, levels of genetic diversity and LD in field populations of the major human malaria parasite P. vivax remain little characterized. Results: We examined single-nucleotide polymorphisms (SNPs) and LD patterns across a 100-kb chromosome segment of P. vivax in 238 field isolates from areas of low to moderate malaria endemicity in South America and Asia, where LD tends to be more extensive than in holoendemic populations, and in two monkey-adapted strains (Salvador-I, from El Salvador, and Belem, from Brazil). We found varying levels of SNP diversity and LD across populations, with the highest diversity and strongest LD in the area of lowest malaria transmission. We found several clusters of contiguous markers with rare meiotic recombination and characterized a relatively conserved haplotype structure among populations, suggesting the existence of recombination hotspots in the genome region analyzed. Both silent and nonsynonymous SNPs revealed substantial between-population differentiation, which accounted for similar to 40% of the overall genetic diversity observed. Although parasites clustered according to their continental origin, we found evidence for substructure within the Brazilian population of P. vivax. We also explored between-population differentiation patterns revealed by loci putatively affected by natural selection and found marked geographic variation in frequencies of nucleotide substitutions at the pvmdr-1 locus, putatively associated with drug resistance. Conclusion: These findings support the feasibility of genome-wide association studies in carefully selected populations of P. vivax, using relatively low densities of markers, but underscore the risk of false positives caused by population structure at both local and regional levels.

Phase transitions and spatially ordered counterion association in ionic-lipid membranes: A statistical model

We propose a statistical model to account for the gel-fluid anomalous phase transitions in charged bilayer- or lamellae-forming ionic lipids. The model Hamiltonian comprises effective attractive interactions to describe neutral-lipid membranes as well as the effect of electrostatic repulsions of the discrete ionic charges on the lipid headgroups. The latter can be counterion dissociated (charged) or counterion associated (neutral), while the lipid acyl chains may be in gel (low-temperature or high-lateral-pressure) or fluid (high-temperature or low-lateral-pressure) states. The system is modeled as a lattice gas with two distinct particle types-each one associated, respectively, with the polar-headgroup and the acyl-chain states-which can be mapped onto an Ashkin-Teller model with the inclusion of cubic terms. The model displays a rich thermodynamic behavior in terms of the chemical potential of counterions (related to added salt concentration) and lateral pressure. In particular, we show the existence of semidissociated thermodynamic phases related to the onset of charge order in the system. This type of order stems from spatially ordered counterion association to the lipid headgroups, in which charged and neutral lipids alternate in a checkerboard-like order. Within the mean-field approximation, we predict that the acyl-chain order-disorder transition is discontinuous, with the first-order line ending at a critical point, as in the neutral case. Moreover, the charge order gives rise to continuous transitions, with the associated second-order lines joining the aforementioned first-order line at critical end points. We explore the thermodynamic behavior of some physical quantities, like the specific heat at constant lateral pressure and the degree of ionization, associated with the fraction of charged lipid headgroups.

Non-Cardiac Surgery in Developing Countries: Epidemiological Aspects and Economical Opportunities - The Case of Brazil

Background: Worldwide distribution of surgical interventions is unequal. Developed countries account for the majority of surgeries and information about non-cardiac operations in developing countries is scarce. The purpose of our study was to describe the epidemiological data of non-cardiac surgeries performed in Brazil in the last years. Methods and Findings: This is a retrospective cohort study that investigated the time window from 1995 to 2007. We collected information from DATASUS, a national public health system database. The following variables were studied: number of surgeries, in-hospital expenses, blood transfusion related costs, length of stay and case fatality rates. The results were presented as sum, average and percentage. The trend analysis was performed by linear regression model. There were 32,659,513 non-cardiac surgeries performed in Brazil in thirteen years. An increment of 20.42% was observed in the number of surgeries in this period and nowadays nearly 3 million operations are performed annually. The cost of these procedures has increased tremendously in the last years. The increment of surgical cost was almost 200%. The total expenses related to surgical hospitalizations were more than $10 billion in all these years. The yearly cost of surgical procedures to public health system was more than $1.27 billion for all surgical hospitalizations, and in average, U$445.24 per surgical procedure. The total cost of blood transfusion was near $98 million in all years and annually approximately $10 million were spent in perioperative transfusion. The surgical mortality had an increment of 31.11% in the period. Actually, in 2007, the surgical mortality in Brazil was 1.77%. All the variables had a significant increment along the studied period: r square (r(2)) = 0.447 for the number of surgeries (P = 0.012), r(2) = 0.439 for in-hospital expenses (P = 0.014) and r(2) = 0.907 for surgical mortality (P = 0.0055). Conclusion: The volume of surgical procedures has increased substantially in Brazil through the past years. The expenditure related to these procedures and its mortality has also increased as the number of operations. Better planning of public health resource and strategies of investment are needed to supply the crescent demand of surgery in Brazil.

Pycnoscelus surinamensis (Linnaeus, 1758) (Blaberoidea: Blaberidae), a cockroach with a possible association with the ant Brachymyrmex cordemoyi Forel, 1895 (Hymenoptera: Formicidae) and which may be exhibiting a domiciliation trend.

In the present paper, we report on the occurrence of the cockroach Pycnoscelus surinamensis (Linnaeus, 1758) in Brachymyrmex cordemoyi Forel, 1895 nests, indicating a possible symbiosis between these two species. Also, the finding of intradomicile P. surinamensis nymphs may indicate this species is extending its habitat to human habitations, i.e. changing its ecological category from peridomestic to domestic.

Association Between Urinary Incontinence in Elderly Patients and Caregiver Burden in the City of Sao Paulo/Brazil: Health, Wellbeing, and Ageing Study

Aim: Some elderly patients with incontinence require the care of third parties, known as caregivers. Such care can occur on a daily basis leaving little opportunity for the caregiver to take care of himself/herself. The aims are to assess the association between urinary incontinence in elderly patients and caregiver burden and identify independent factors for caregiver`s burden in the city of Sao Paulo, Brazil. Methods: The Pan-American Health Organization and World Health Organization coordinated a multicenter study named Health, Wellbeing and Aging (SABE Study) in elderly people living in seven countries of Latin America and the Caribbean. In Brazil, the study population carried out in Sao Paulo in the year 2000 and reassessed in 2006 (COHORT A). Urinary incontinence was assessed by ICIQ-SF and caregiver burden by means of Zarit Burden Scale. Results: A total of 327 patients with caregivers were included in the study. The general prevalence of urinary incontinence was 25.8%, higher among the women. There was a significant positive association between caregiver burden and incontinent patients, demonstrating that urinary incontinence in elderly patients produced greater caregiver burden. In the present study, the variables with significant correlations were assessed using the multivariate logistic regression model. Category 2 of the ICIQ-SF (incontinent patients) increased the chances of caregiver burden 1.96-fold in comparison to Category 1 (continent patients). Likewise, the category of impaired cognition increased the chances of caregiver burden 2.34-fold. Conclusions: Urinary incontinence and cognitive impairment in elderly patients were associated to an increase in caregiver burden. Neurourol. Urodynam. 30:1281-1285, 2011. (C) 2011 Wiley-Liss, Inc.

Association between nutritional status and blood pressure in schoolchildren

The aim of this study was to analyze the association between nutritional status and blood pressure in adolescents from a private school. Were recruited 316 young of both gender with age raging from 11 to 15 years old. Were measured body mass, stature, systolic blood pressure and diastolic blood pressure. The statistic procedures were composed by median, interquartile range, chi-square test and Poisson regression. The prevalence of overweight and high blood pressure was significantly higher in boys (38% and 24%, respectively) when compared to girls (19.3% and 14.4%, respectively). Overweight adolescents presented a higher risk (about 2-fold) to develop high blood pressure. In conclusion, overweight seems to be associate with high blood pressure in adolescents.

Combined heuristic with fuzzy system to transmission system expansion planning

A heuristic algorithm that employs fuzzy logic is proposed to the power system transmission expansion planning problem. The algorithm is based on the divide to conquer strategy, which is controlled by the fuzzy system. The algorithm provides high quality solutions with the use of fuzzy decision making, which is based on nondeterministic criteria to guide the search. The fuzzy system provides a self-adjusting mechanism that eliminates the manual adjustment of parameters to each system being solved. (C) 2010 Elsevier B.V. All rights reserved.

Multi-objective analysis of impacts of distributed generation placement on the operational characteristics of networks for distribution system planning

Recent advances in energy technology generation and new directions in electricity regulation have made distributed generation (DG) more widespread, with consequent significant impacts on the operational characteristics of distribution networks. For this reason, new methods for identifying such impacts are needed, together with research and development of new tools and resources to maintain and facilitate continued expansion towards DG. This paper presents a study aimed at determining appropriate DG sites for distribution systems. The main considerations which determine DG sites are also presented, together with an account of the advantages gained from correct DG placement. The paper intends to define some quantitative and qualitative parameters evaluated by Digsilent (R), GARP3 (R) and DSA-GD software. A multi-objective approach based on the Bellman-Zadeh algorithm and fuzzy logic is used to determine appropriate DG sites. The study also aims to find acceptable DG locations both for distribution system feeders, as well as for nodes inside a given feeder. (C) 2010 Elsevier Ltd. All rights reserved.

Financial distress, financial constraint and investment decision: Evidence from Brazil

This paper analyses the presence of financial constraint in the investment decisions of 367 Brazilian firms from 1997 to 2004, using a Bayesian econometric model with group-varying parameters. The motivation for this paper is the use of clustering techniques to group firms in a totally endogenous form. In order to classify the firms we used a hybrid clustering method, that is, hierarchical and non-hierarchical clustering techniques jointly. To estimate the parameters a Bayesian approach was considered. Prior distributions were assumed for the parameters, classifying the model in random or fixed effects. Ordinate predictive density criterion was used to select the model providing a better prediction. We tested thirty models and the better prediction considers the presence of 2 groups in the sample, assuming the fixed effect model with a Student t distribution with 20 degrees of freedom for the error. The results indicate robustness in the identification of financial constraint when the firms are classified by the clustering techniques. (C) 2010 Elsevier B.V. All rights reserved.

Evaluating an Agile Method for Planning and Controlling Innovative Projects

This article presents an extensive investigation carried out in two technology-based companies of the So Carlos technological pole in Brazil. Based on this multiple case study and literature review, a method, entitled hereafter IVPM2, applying agile project management (APM) principles was developed. After the method implementation, a qualitative evaluation was carried out by a document analysis and questionnaire application. This article shows that the application of this method at the companies under investigation evidenced the benefits of using simple, iterative, visual, and agile techniques to plan and control innovative product projects combined with traditional project management best practices, such as standardization.

Planning and operation of large-scale water distribution systems with preemptive priorities

This paper describes the development of an optimization model for the management and operation of a large-scale, multireservoir water supply distribution system with preemptive priorities. The model considers multiobjectives and hedging rules. During periods of drought, when water supply is insufficient to meet the planned demand, appropriate rationing factors are applied to reduce water supply. In this paper, a water distribution system is formulated as a network and solved by the GAMS modeling system for mathematical programming and optimization. A user-friendly interface is developed to facilitate the manipulation of data and to generate graphs and tables for decision makers. The optimization model and its interface form a decision support system (DSS), which can be used to configure a water distribution system to facilitate capacity expansion and reliability studies. Several examples are presented to demonstrate the utility and versatility of the developed DSS under different supply and demand scenarios, including applications to one of the largest water supply systems in the world, the Sao Paulo Metropolitan Area Water Supply Distribution System in Brazil.

New reconciliation model for gold industry

Reconciliation can be divided into stages, each stage representing the performance of a mining operation, such as: long-term estimation, short-term estimation, planning, mining and mineral processing. The gold industry includes another stage which is the budget, when the company informs the financial market of its annual production forecast. The division of reconciliation into stages increases the reliability of the annual budget informed by the mining companies, while also detecting and correcting the critical steps responsible for the overall estimation error by the optimization of sampling protocols and equipment. This paper develops and validates a new reconciliation model for the gold industry, which is based on correct sampling practices and the subdivision of reconciliation into stages, aiming for better grade estimates and more efficient control of the mining industry`s processes, from resource estimation to final production.