Sex differences and correlates of poor glycaemic control in type 2 diabetes: a cross-sectional study in Brazil and Venezuela.

OBJECTIVE: Examine whether glycaemic control varies according to sex and whether the latter plays a role in modifying factors associated with inadequate glycaemic control in patients with type 2 diabetes (T2D) in Brazil and Venezuela. DESIGN, SETTING AND PARTICIPANTS: This was a cross-sectional, nationwide survey conducted in Brazil and Venezuela from February 2006 to June 2007 to obtain information about glycaemic control and its determinants in patients with diabetes mellitus attending outpatient clinics. MAIN OUTCOME MEASURES: Haemoglobin A1c (HbA1c) level was measured by liquid chromatography, and patients with HbA1c ≥7.0% (53 mmol/mol) were considered to have inadequate glycaemic control. The association of selected variables with glycaemic control was analysed by multivariate linear regression, using HbA1c as the dependent variable. RESULTS: A total of 9418 patients with T2D were enrolled in Brazil (n=5692) and in Venezuela (n=3726). They included 6214 (66%) women and 3204 (34%) men. On average, HbA1c levels in women were 0.13 (95% CI 0.03 to 0.24; p=0.015) higher than in men, after adjusting for age, marital status, education, race, country, body mass index, duration of disease, complications, type of healthcare, adherence to diet, adherence to treatment and previous measurement of HbA1c. Sex modified the effect of some factors associated with glycaemic control in patients with T2D in our study, but had no noteworthy effect in others. CONCLUSIONS: Women with T2D had worse glycaemic control than men. Possible causes for poorer glycaemic control in women compared with men include differences in glucose homeostasis, treatment response and psychological factors. In addition, sex modified factors associated with glycaemic control, suggesting the need to develop specific treatment guidelines for men and women

The role of drug use sequencing pattern in further problematic use of alcohol, tobacco, cannabis, and other drugs

Background: There has been considerable debate regarding what typically occurs after experimentation with drugs throughout the life of young people who used various drugs. Aims: To evaluate the clinical importance of the most common sequence for the first use of a drug by two models (the “gateway model” and the “alternative model”, which is the most popular sequence for Brazilian university students according to a previous study) regarding the problematic use of alcohol, tobacco, cannabis and other illegal drugs, assessed by ASSIST. Method: People who had already experimented with three or more drugs across different stages of the two models were selected from a representative sample of university students from 27 Brazilian capitals (n = 12 711). Findings: There were no differences regarding the problematic use of the most consumed drugs in Brazil (alcohol, tobacco and cannabis) between the models. Multiple drug seekers and violators had more problematic use of illegal drugs other than cannabis than individuals in the model sequence. However, in the case of violators, this was only evident in the alternative model. Conclusions: Multiple drug seekers and violators deserve special attention due to their increased risk of problematic use of other illegal drugs

The role of first use of inhalants within sequencing pattern of first use of drugs among Brazilian university students.

The present study investigated the role of first use of inhalants within a first drug sequencing pattern. In a representative sample of university students from 27 Brazilian capitals (n = 12,711), we analyzed the patterns of transition from/to first use of inhalants to/from the first use of alcohol, tobacco, cannabis, cocaine, hallucinogens, ecstasy, amphetamines, prescription opioids, and tranquilizers. Cox proportional hazards models were used to analyze data. Drugs that were not specified as the pair of drugs tested in each model were included as time-varying covariates in all models. In this sample, first use of inhalants was preceded only by the first use of alcohol and tobacco. However, first use of inhalants preceded first use of cannabis, amphetamines, cocaine, and tranquilizers. First use of inhalants preceded the first use of prescription opioids, and vice versa. This study highlights the need to intervene early with youths who are at risk of or just beginning to use inhalants, because this class of drugs seems to be the first illegal drug in Brazil to be experimented by respondents in our sample. There is also a call for attention to individuals who have already first used inhalants because of their higher chance to experiment with other drugs such as cannabis, cocaine, and prescription drugs. All these findings show an in-transition culture of drug use, which should be tracked through time, because some classical models (i.e., gateway model) might be outdated and might also not fit within different settings

Use transition between illegal drugs among Brazilian university students

Purpose: The aim of the present study was to test whether the first use of an illicit drug increases the chance of first use of other illicit drugs. Method: The transitions from the first use of a drug to the first use of another drug were analyzed. Comparisons were made between first drug users and non-users. Survival analysis methods were used to compare the cumulative probability of second drug use after adjusting for socio-demographic covariates and the intermediate use of alcohol and/or tobacco. A total of 12,721 Brazilian university students participated in this study. Results: Inhalants and marijuana were used prior to the use of several other drugs, whereas the opposite pattern was not found. Ecstasy was used before other drugs in several instances. Other well-examined drugs, such as amphetamines, cocaine and hallucinogens, were used both before and after other illicit drugs without any marked predominance for either of the two roles. Conclusions: This study supports the role of the use of marijuana and inhalants almost exclusively before the use of other illicit drugs, whereas the use of ecstasy has an opposite role. These roles could be linked to the prevalence of lifetime use and whether individuals were at an earlier or later age during experimentation

Investigating dimensionality and measurement bias of DSM-5 alcohol use disorder in a representative sample of the largest metropolitan area in South America

Background: Given the recent launch of a new diagnostic classification (DSM-5) for alcohol use disorders (AUD), we aimed to investigate its dimensionality and possible measurement bias in a non-U.S. sample. Methods: The current analyses were restricted to 948 subjects who endorsed drinking at least one drink per week in the past year from a sample of 5037 individuals. Data came from São Paulo Megacity Project (which is part of World Mental Health Surveys) collected between 2005 and 2007. First, exploratory factor analysis (EFA) was carried out to test for the best dimensional structure for DSM-5-AUD criteria. Then, item response theory (IRT) was used to investigate the severity and discrimination properties of each criterion of DSM-5-AUD. Finally, differential criterion functioning (DCF) were investigated by socio-demographics (income, gender, age, employment status, marital status and education). All analyses were performed in Mplus software taking into account complex survey design features. Results: The best EFA model was a one-dimensional model. IRT results showed that the criteria “Time Spent” and “Given Up” have the highest discrimination and severity properties, while the criterion “Larger/Longer” had the lowest value of severity, but an average value of discrimination. Only female gender had DCF both at criterion- and factor-level, rendering measurement bias. Conclusion: This study reinforces the existence of a DSM-5-AUD continuum in the largest metropolitan area of South America, including subgroups that had previously higher rates of alcohol use (lower educational/income levels). Lower DSM-5-AUD scores were found in women

DSM-5 latent classes of alcohol users in a population-based sample: Results from the São Paulo Megacity Mental Health Survey, Brazil

Background: We aimed to identify different categorical phenotypes based upon the DSM-V criteria of alcohol use disorders (AUD) among alcohol users who had at least one drink per week in the past year (n = 948). Methods: Data are from the São Paulo Megacity Mental Health Survey collected in 2005–2007, as part of the World Mental Health Survey Initiative. A latent class analysis of the 11 DSM-5-AUD criteria was performed using Mplus, taking into account complex survey design features. Weighted logistic regression models were used to examine demographic correlates of the DSM-5-AUD latent classes. Results: The best latent-class model was a three-class model. We found a “non-symptomatic class” (69.7%), a “use in larger amounts class” (23.2%), defined by high probability (>70%) of the “use in larger amounts” criterion only, and a “high-moderate symptomatic class” (7.1%), defined by high-moderate probability of all the 11 AUD criteria. Compared to those in the non-symptomatic class, individuals in the “high-moderate symptomatic class” were more likely to have been married, have lower educational attainment and to be unemployed or in non-regular/informal employment. Those on the “use in larger amounts class” were more likely to have been married or never married. Conclusion: The two symptomatic classes clearly represented the dimensionality of the new proposed AUD criteria, and could be more specifically targeted by different prevention or treatment strategies. DSM-5-AUD has the advantage of shedding light on risky drinkers included in the “use in larger amounts class”, allowing for preventive interventions, which will reach a large number of individuals

A eficácia do milnaciprano em pacientes ambulatoriais com transtorno depressivo maior não respondedores ao tratamento com ISRSs: um estudo aberto de 12 semanas

BACKGROUND: The objective of this study is to evaluate the efficacy of milnacipran in outpatients experiencing severe MDD non-respondent to adequate time and dosing of SSRI therapy. METHODS: A 12 week multi-centric study open study was designed to evaluate the efficacy of milnacipran after a SRRI trial failure. Complete remission (HAMD-17 < 8) was the principal outcome. Secondary outcomes were response (HAM &gt; 50%), CGI and quality of life measure (WHOQOL-Bref). RESULTS: The mean HAMD-17 score of the sample was 27 (7.2). The remission rates for minalcipran were 17.5% and response 61.3%. At baseline, 70.9% of the patients were markedly or severely ill. At treatment end, 48.1% of the patients were normal asymptomatic or borderline and 20.2% were mildly ill. Also, the four domains of WHOQOL-Bref, a generic instrument of Quality of Life, presented statistical and clinical differences. DISCUSSION: Our findings suggest that milnacipran is a possible option to be used in patients that were non-respondents to SSRIs. Since there is no evidence in literature that one single antidepressant is the best second step when an SSRI fail, milnacipran should be considered in the case of severe depressed patients.CONTEXTO: O objetivo deste estudo é avaliar a eficácia do milnaciprano em pacientes ambulatoriais com depressão maior grave que não respondem em tempo e em dosagem adequados à terapia com ISRSs. MÉTODOS: Um estudo aberto multicêntrico com a duração de 12 semanas foi elaborado para avaliar a eficácia do milnaciprano após falha em um experimento com ISRS. Remissão completa (HAMD-17 < 8) foi o desfecho principal. Os desfechos secundários foram resposta (HAM &gt; 50%), CGI e avaliação da qualidade de vida (WHOQOL-Bref). RESULTADOS: O escore HAMD-17 médio da amostra foi de 27 (7,2). As taxas de remissão com o milnaciprano foram de 17,5%, e as de resposta, 61,3%. Na linha de base, 70,9% dos pacientes foram classificados como gravemente sintomáticos. Ao final do tratamento, 48,1% dos pacientes foram classificados como normais assintomáticos ou sintomáticos limítrofes e 20,2% eram moderadamente sintomáticos. Além disso, os quatro domínios do WHOQOL-Bref, um instrumento genérico de mensuração de qualidade de vida, apresentou diferenças clínicas e estatísticas: CONCLUSÃO: Nossos resultados sugerem que o milnaciprano é uma possível opção para pacientes que não respondem a ISRSs. Uma vez que não há evidências na literatura de um antidepressivo que seja a melhor opção quando um ISRS falha, o uso do milnaciprano deveria ser considerado em casos de pacientes com depressão severa

Hierarchical information clustering by means of topologically embedded graphs

We introduce a graph-theoretic approach to extract clusters and hierarchies in complex data-sets in an unsupervised and deterministic manner, without the use of any prior information. This is achieved by building topologically embedded networks containing the subset of most significant links and analyzing the network structure. For a planar embedding, this method provides both the intra-cluster hierarchy, which describes the way clusters are composed, and the inter-cluster hierarchy which describes how clusters gather together. We discuss performance, robustness and reliability of this method by first investigating several artificial data-sets, finding that it can outperform significantly other established approaches. Then we show that our method can successfully differentiate meaningful clusters and hierarchies in a variety of real data-sets. In particular, we find that the application to gene expression patterns of lymphoma samples uncovers biologically significant groups of genes which play key-roles in diagnosis, prognosis and treatment of some of the most relevant human lymphoid malignancies.Comment: 33 Pages, 18 Figures, 5 Table

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected