Early life course determinants of young adults' gambling behaviour. An Australian Longitudinal Study

Problem gambling represents a public concern as both a social and health issue. Available evidence shows problem gambling is associated with a range of psychological disorders, criminality, and disruption to families. While gambling itself may represent a pleasurable pursuit for the majority, for a proportion, gambling-related activities may assume many of the characteristics of an addiction and have the capacity to undermine individuals� mental and physical health, social relationships, financial independence, as well as the financial and psychological wellbeing of their families and/or friends. The objectives of this study are based on the need to increase our understanding of gambling behaviour, its antecedents, as well its influence on the health and wellbeing of gamblers and their families. One of the most important and unresolved issues in gambling research is whether the mental health and social/family correlates of gambling precede or follow gambling behaviour. This report focuses on this issue.

Molecular determinants of improved cathepsin B inhibition by new cystatins obtained by DNA shuffling

Background: Cystatins are inhibitors of cysteine proteases. The majority are only weak inhibitors of human cathepsin B, which has been associated with cancer, Alzheimer's disease and arthritis. Results: Starting from the sequences of oryzacystatin-1 and canecystatin-1, a shuffling library was designed and a hybrid clone obtained, which presented higher inhibitory activity towards cathepsin B. This clone presented two unanticipated point mutations as well as an N-terminal deletion. Reversing each point mutation independently or both simultaneously abolishes the inhibitory activity towards cathepsin B. Homology modeling together with experimental studies of the reverse mutants revealed the likely molecular determinants of the improved inhibitory activity to be related to decreased protein stability. Conclusion: A combination of experimental approaches including gene shuffling, enzyme assays and reverse mutation allied to molecular modeling has shed light upon the unexpected inhibitory properties of certain cystatin mutants against Cathepsin B. We conclude that mutations disrupting the hydrophobic core of phytocystatins increase the flexibility of the N-terminus, leading to an increase in inhibitory activity. Such mutations need not affect the inhibitory site directly but may be observed distant from it and manifest their effects via an uncoupling of its three components as a result of increased protein flexibility.

Evaluation of nutritional and genetic determinants of total homocysteine, methylmalonic acid and S-adenosylmethionine/S-adenosylhomocysteine values in Brazilian childbearing-age women

Background: Cobalamin (Cbl) and folate deficiencies and gene polymorphism of key enzymes or carriers can impair homocysteine metabolism and may change the serum values of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH). We investigated the nutritional and genetic determinants for total homocysteine (tHcy), methylmalonic acid (MMA) and SAM/SAH in healthy Brazilian childbearing-age women. Methods: Serum concentrations of Cbl, folate, red blood cell folate, ferritin, tHcy, MMA, SAM, SAH and other metabolites were measured in 102 healthy unrelated women. The genotypes for MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G, TC2 C776G, TC2 A67G and RFCI A80G gene polymorphisms were identified by PCR-RFLP. Results: Serum folate and Cbl were inversely correlated with tHcy and serum MMA, respectively. Cbl deficiency was associated with increased MMA and reduced alpha-aminobutyrate, serine and N-methylglycine concentrations. No variable was associated with SAM/SAH ratio. In addition, gene polymorphisms were not selected as determinants for tHcy, MMA and SAM/SAH ratio. Iron, Cbl and folate deficiencies were found respectively in 30.4%, 22.5% and 2.0% of individuals studied. Conclusions: There was a high frequency of Cbl and iron deficiency in this group of childbearing-age women. Serum folate and Cbl were the determinants of serum tHcy and MMA concentration, respectively. (c) 2007 Elsevier B.V. All rights reserved.

Determinants of beta-lactam resistance in meningitis-causing Enterobacteriaceae in Brazil

This study analyzed resistance determinants in extended-spectrum beta-lactamase (ESBL)-producing enterobacteria and the epidemiology of 11 Escherichia coli isolates obtained from meningitis patients in a region of Brazil from 2000 to 2005. ESBL-encoding genes and their genetic environment were investigated by PCR and sequencing. The gene bla(CTX-M-2) was identified in 3 different enterobacteria (E. coli. Serratia marcescens, and Proteus mirabilis) downstream of the insertion sequence ISCR1 (localized in class 1 integrons), hut not as part of the resistance cassettes region. Multi locus sequence typing (MLST) was used to investigate genetic relationships between the 11 E. coil isolates in this study and strains associated with meningitis in the E. coil MLST database. MLST analysis indicated high genetic diversity among isolates, and no significant genetic relationship was identified with meningitis-causing E. coil in the database. The results in this report reinforce the need to be attentive to meningitis suspected to be due to ESBL-producing enterobacterial isolates, especially where ESBL epidemiology is well known.

Developing a framework for assessment of the environmental determinants of walking and cycling

The focus for interventions and research on physical activity has moved away from vigorous activity to moderate-intensity activities, such as walking. In addition, a social ecological approach to physical activity research and practice is recommended. This approach considers the influence of the environment and policies on physical activity. Although there is limited empirical published evidence related to the features of the physical environment that influence physical activity, urban planning and transport agencies have developed policies and strategies that have the potential to influence whether people walk or cycle in their neighbourhood. This paper presents the development of a framework of the potential environmental influences on walking and cycling based on published evidence and policy literature, interviews with experts and a Delphi study. The framework includes four features: functional, safety, aesthetic and destination; as well as the hypothesised factors that contribute to each of these features of the environment. In addition, the Delphi experts determined the perceived relative importance of these factors. Based on these factors, a data collection tool will be developed and the frameworks will be tested through the collection of environmental information on neighbourhoods, where data on the walking and cycling patterns have been collected previously. Identifying the environmental factors that influence walking and cycling will allow the inclusion of a public health perspective as well as those of urban planning and transport in the design of built environments. (C) 2002 Elsevier Science Ltd., All rights reserved.

Hierarchical determinants of capital structure

We analyze the influence of time-, firm-, industry- and country-level determinants of capital structure. First, we apply hierarchical linear modeling in order to assess the relative importance of those levels. We find that time and firm levels explain 78% of firm leverage. Second, we include random intercepts and random coefficients in order to analyze the direct and indirect influences of firm/industry/country characteristics on firm leverage. We document several important indirect influences of variables at industry and country-levels on firm determinants of leverage, as well as several structural differences in the financial behavior between firms of developed and emerging countries. (C) 2010 Elsevier B.V. All rights reserved.

The economic determinants of the Brazilian nominal term structure of interest rates

The purpose of this study is to identify the effects of monetary policy and macroeconomic shocks on the dynamics of the Brazilian term structure of interest rates. We estimate a near-VAR model under the identification scheme proposed by Christiano et al. (1996, 1999). The results resemble those of the US economy: monetary policy shocks that flatten the term structure of interest rates. We find that monetary policy shocks in Brazil explain a significantly larger share of the dynamics of the term structure than in the USA. Finally, we analyse the importance of standard macroeconomic variables (e. g. GDP, inflation and measure of country risk) to the dynamics of the term structure in Brazil.

The determinants of default risk in Brazil

We formulated a general unrestricted model of the Brazilian Emerging Markets Bond Index Plus (EMBI+) spreads, a proxy for the country`s default risk. Employing algorithms that perform automated model selection, we found that macroeconomic fundamentals, such as current account deficit ratio to gross domestic product, public deficit ratio to gross domestic product and imports over foreign exchange reserves, can explain a great part of the variation in EMBI+ spreads. There is also robust evidence of systematic contagion from Argentina and Mexico and that the variance of the spread also affects its mean.

Molecular adaptability of nucleoside diphosphate kinase b from trypanosomatid parasites: stability, oligomerization and structural determinants of nucleotide binding

Nucleoside diphosphate kinases play a crucial role in the purine-salvage pathway of trypanosomatid protozoa and have been found in the secretome of Leishmania sp., suggesting a function related to host-cell integrity for the benefit of the parasite. Due to their importance for housekeeping functions in the parasite and by prolonging the life of host cells in infection, they become an attractive target for drug discovery and design. In this work, we describe the first structural characterization of nucleoside diphosphate kinases b from trypanosomatid parasites (tNDKbs) providing insights into their oligomerization, stability and structural determinants for nucleotide binding. Crystallographic studies of LmNDKb when complexed with phosphate, AMP and ADP showed that the crucial hydrogen-bonding residues involved in the nucleotide interaction are fully conserved in tNDKbs. Depending on the nature of the ligand, the nucleotide-binding pocket undergoes conformational changes, which leads to different cavity volumes. SAXS experiments showed that tNDKbs, like other eukaryotic NDKs, form a hexamer in solution and their oligomeric state does not rely on the presence of nucleotides or mimetics. Fluorescence-based thermal-shift assays demonstrated slightly higher stability of tNDKbs compared to human NDKb (HsNDKb), which is in agreement with the fact that tNDKbs are secreted and subjected to variations of temperature in the host cells during infection and disease development. Moreover, tNDKbs were stabilized upon nucleotide binding, whereas HsNDKb was not influenced. Contrasts on the surface electrostatic potential around the nucleotide-binding pocket might be a determinant for nucleotide affinity and protein stability differentiation. All these together demonstrated the molecular adaptation of parasite NDKbs in order to exert their biological functions intra-parasite and when secreted by regulating ATP levels of host cells.

Political Parties and Governors as Determinants of Legislative Behavior in Brazil`s Chamber of Deputies, 1988-2006

This article examines the relative importance of regional and national forces in shaping the behavior of Brazilian legislators at the national level. A widely held view is that national legislators respond to state pressures in making decisions, rather than pressures from the national government. Governors not only can influence national debates but also can determine outcomes by exerting control over their states` legislative delegations. This article examines a dataset of all roll-call votes in the Chamber of Deputies between 1989 and 2006 to isolate and evaluate the impact of local pressures on legislative voting. Spanning the terms of five presidents and five different congresses, the data show that the local influence is weaker than the national on the voting decisions of individual legislators and the voting cohesion of state delegations. Alternative institutional resources allow the central government to counteract the centrifugal pressures of federalism and other institutional influences.

Determinants of left ventricular mass and presence of metabolic risk factors in normotensive individuals

Background: Insulin resistance and obesity are recognized as left ventricular (LV) mass determinants independent of blood pressure (BP). Prevalence of LV hypertrophy (LVH) and the relationship between LV mass to body composition and metabolic variables were evaluated in normotensive individuals as participants of a population-based study. Methods: LV mass was measured using the second harmonic image by M-mode 2D guided echocardiography in 326 normotensive subjects (mean 47 +/- 9.4 years). Fasting serum lipids and glucose, BP, body composition and waist circumference (WC) were recorded during a clinic visit. Results: Applying a normalization criterion not related to body weight (g/height raised to the power 2.7) and the cut-off points of 47.7 (men) and 46.6 g/m(2.7) (women), LVH was found in 7.9% of the sample. Univariate analysis showed LV mass (g/m(2.7)) related to age, body mass index (BMI), WC, fat and lean body mass, systolic and diastolic BP, and metabolic variables (cholesterol, HDL-c, triglycerides and glucose). In multivariate analysis only BMI and age-adjusted systolic BP remained as independent predictors of LV mass, explaining 31% and 5% of its variability. Removing BMI from the model, WC, age-adjusted systolic BP and lean mass remained independent predictors, explaining 25.0%, 4.0% and 1.5% of LV mass variability, respectively. After sex stratification, LV mass predictors were WC (8%) and systolic BP (5%) in men and WC (36%) and systolic BP (3%) in women. Conclusion: BMI in general and particularly increased abdominal adiposity (WC as surrogate) seems to account for most of LV mass increase in normotensive individuals, mainly in women. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Autopsy-Proven Determinants of Immediate Fire Death in Lungs

In immediate fire deaths, pulmonary injury may be the main source of mortality, being important to document the histologic findings for the purpose of excluding other modes of death, such as from asphyxia with no gross findings. In this context, a group of morphologic determinants have been targeted with useful makers of pulmonary injury. To facilitate the determination of whether an individual was deceased before the start of a fire and validate the importance of parenchymal alterations in pulmonary injury in fire deaths, we studied lungs in victims of fire (N = 28) and suffocation (N = 40), creating a mathematical model using cluster analysis. For this purpose, a semiquantitative analysis of the distal parenchyma was performed to evaluate the amount of bronchiolar dilatation, overinsufflation (ductal and alveolar), collapse (ductal and alveolar), passive congestion, alveolar edema, and hemorrhage (interstitial and alveolar). These 7 histologic determinants were useful to discriminate fire (bronchiolar dilatation, ductal overinsuflation, alveolar overinsuflation, alveolar hemorrhage) from suffocation lung injuries (alveolar collapse, congestion, and edema). We conclude that these determinants should be included in the routine of forensic pathology.

Biopsy-Proven Pulmonary Determinants of Heart Disease

Heart disease (HD) can stress the alveolar blood-gas barrier, resulting in parenchymal inflammation and remodeling. Patients with HD may therefore display any of the symptoms commonly attributed to primary pulmonary disease, although tissue documentation of corresponding changes through surgical lung biopsy (SLB) is rarely done. Intent on exploring the basis of HD-related alveolar-capillary barrier dysfunction, a retrospective analysis of SLB histopathology was conducted in patients with clinically diagnosed HD, diffuse pulmonary infiltrates, and no evidence of primary pulmonary disease. Patients eligible for the study had a clinical diagnosis of heart disease, acute or chronic, and presented with diffuse infiltrates on chest X-ray. All qualified subjects (N = 23) who underwent diagnostic SLB between January 1982 and December 2005 were subsequently examined. Specific biopsy parameters investigated included demonstrable edema, siderophage influx, hemorrhage, venous and lymphatic ectasia, vascular sclerosis, capillary congestion, and fibroblast proliferation. Based on observed alveolar-capillary barrier (ACB) alterations, three main morphologic groups emerged: one group (6 patients) with alveolar edema; a second group (11 patients) characterized by pulmonary congestion; and a final group (6 patients) showing microscopic foci of acute ACB lung injury. Alveolar-capillary stress due to acute high-pressure or volume overload often manifests as diffuse pulmonary infiltrates with variable but generally predictable histopathology. In patients with biopsy-proven alveolar edema, pulmonary congestion, or acute microscopic lung injury, the clinician must be alert for the possibility of primary heart disease, particularly if the patient is elderly or when a history of myocardial, valvular, or coronary vascular disease exists.

Prognostic heterogeneity among patients with chronic stable coronary disease: determinants of long-term mortality after treatment with percutaneous intervention

Aims: To evaluate the risk and predictors of death in a large population of patients with stable coronary disease treated with percutaneous intervention. Methods and results: The study population comprised 1,276 patients with chronic angina or silent ischaemia who underwent elective coronary angioplasty. Baseline and in-hospital mortality data were prospectively collected for all patients during the index hospitalisation. Post-discharge outcome was assessed at out-patient clinic, by review of the patients` records, or direct phone contact. Deaths were classified as cardiac and non-cardiac. Age, peripheral arterial disease, congestive heart failure with NYHA class Ill, triple-vessel disease, and procedural success (i.e. angiographic success for all lesions in the absence of pen-procedural infarction) remained as multivariate independent predictors of death. For the entire population 4-year cumulative all-cause and cardiac mortality were respectively 5.4% and 4.1%. Four-year mortality for patients without any multivariate predictor was 2.4%, while for patients with two or more predictors the death rate was 16.3% after four years. Conclusions: Patients with stable coronary disease undergoing percutaneous treatment have an overall low mortality rate after four years. Nevertheless, stable patients comprise a heterogeneous population in terms of risk profile, ranging from patients at very low risk of late death to individuals with a poor long-term prognosis.