A one-year monitoring of nicotine use in sport: frontier between potential performance enhancement and addiction issues

Tobacco consumption is a global epidemic responsible for a vast burden of disease. With pharmacological properties sought-after by consumers and responsible for addiction issues, nicotine is the main reason of this phenomenon. Accordingly, smokeless tobacco products are of growing popularity in sport owing to potential performance enhancing properties and absence of adverse effects on the respiratory system. Nevertheless, nicotine does not appear on the 2011 World Anti-Doping Agency (WADA) Prohibited List or Monitoring Program by lack of a comprehensive large-scale prevalence survey. Thus, this work describes a one-year monitoring study on urine specimens from professional athletes of different disciplines covering 2010 and 2011. A method for the detection and quantification of nicotine, its major metabolites (cotinine, trans-3-hydroxycotinine, nicotine-N′-oxide and cotinine-N-oxide) and minor tobacco alkaloids (anabasine, anatabine and nornicotine) was developed, relying on ultra-high pressure liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-TQ-MS/MS). A simple and fast dilute-and-shoot sample treatment was performed, followed by hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS) operated in positive electrospray ionization (ESI) mode with multiple reaction monitoring (MRM) data acquisition. After method validation, assessing the prevalence of nicotine consumption in sport involved analysis of 2185 urine samples, accounting for 43 different sports. Concentrations distribution of major nicotine metabolites, minor nicotine metabolites and tobacco alkaloids ranged from 10 (LLOQ) to 32,223, 6670 and 538 ng/mL, respectively. Compounds of interest were detected in trace levels in 23.0% of urine specimens, with concentration levels corresponding to an exposure within the last three days for 18.3% of samples. Likewise, hypothesizing conservative concentration limits for active nicotine consumption prior and/or during sport practice (50 ng/mL for nicotine, cotinine and trans-3-hydroxycotinine and 25 ng/mL for nicotine-N′-oxide, cotinine-N-oxide, anabasine, anatabine and nornicotine) revealed a prevalence of 15.3% amongst athletes. While this number may appear lower than the worldwide smoking prevalence of around 25%, focusing the study on selected sports highlighted more alarming findings. Indeed, active nicotine consumption in ice hockey, skiing, biathlon, bobsleigh, skating, football, basketball, volleyball, rugby, American football, wrestling and gymnastics was found to range between 19.0 and 55.6%. Therefore, considering the adverse effects of smoking on the respiratory tract and numerous health threats detrimental to sport practice at top level, likelihood of smokeless tobacco consumption for performance enhancement is greatly supported.

Religious identity and intercultural dialogue

(Résumé de l'ouvrage) In a world society ruled by economic globalisation, by political interests and theories such as Huntington's «clash of civilisations» that widen the gap between the North and the South, the question should be asked of the role of the religion. To what extent religion and politics can work together? Can faith still be thought as a means of saving the world? Considering that Christianity, Islam and Judaism have much in common, this collection of miscellanies wonders if these religions can join their forces for public benefit. Senior and junior scholars from all over the world, gathered for an interdisciplinary seminar, analyse the contemporary international relationships and geopolitics through the prism of religion, discussing whether it can provide practical solutions to solve conflicts and increase the respect of human rights.

The development of an enzyme-linked immunosorbent assay for Trypanosoma vivax antibodies and its use in epidemiological surveys

There are data indicating that the distribution of Trypanosoma vivax in the Brazilian territory is expanding with potential to reach other areas, where the vectors are present. The detection of anti-trypanosomal antibodies in serum provides important information of the trypanosomal status in cattle herds. For this reason, an enzyme-linked immunosorbent assay (Tv-ELISA-Ab) with crude antigen from one Brazilian isolate of T. vivax was developed and evaluated. The sensitivity and specificity were respectively 97.6 and 96.9%. In the evaluation of cross-reactions, three calves inoculated with T. evansi trypimastigotes blood forms showed optical densities (OD) under the cut-off during the whole experimental period, except one at 45 days post-inoculation. With relation to Babesia bovis, B. bigemina, and Anaplasma marginale, which are endemic hemoparasites in the studied area, the cross-reactions were shown to be 5.7, 5.3, and 1.1%, respectively. The first serological survey of Pantanal and state of Pará showed that T. vivax is widespread, although regions within both areas had significantly different prevalences. Therefore, this Tv-ELISA-Ab may be a more appropriate test for epidemiological studies in developing countries because the diagnostic laboratories in most countries may be able to perform an ELISA, which is not true for polymerase chain reaction.

"I'll look it up on the Web first": barriers and overcoming barriers to consult for sexual dysfunction among young men.

QUESTIONS UNDER STUDY: Our aim was to identify the barriers young men face to consult a health professional when they encounter sexual dysfunctions and where they turn to, if so, for answers. METHODS: We conducted an exploratory qualitative research including 12 young men aged 16-20 years old seen in two focus groups. Discussions were triggered through vignettes about sexual dysfunction. RESULTS: Young men preferred not to talk about sexual dysfunction problems with anyone and to solve them alone as it is considered an intimate and embarrassing subject which can negatively impact their masculinity. Confidentiality appeared to be the most important criterion in disclosing an intimate subject to a health professional. Participants raised the problem of males' accessibility to services and lack of reason to consult. Two criteria to address the problem were if it was long-lasting or considered as physical. The Internet was unanimously considered as an initial solution to solve a problem, which could guide them to a face-to-face consultation if necessary. CONCLUSIONS: Results suggest that Internet-based tools should be developed to become an easy access door to sexual health services for young men. Wherever they consult and for whatever problem, sexual health must be on the agenda.

Cloning and molecular characterization of Trypanosoma cruzi U2, U4, U5, and U6 small nuclear RNAs

Small nuclear RNAs (snRNAs) are important factors in the functioning of eukaryotic cells that form several small complexes with proteins; these ribonucleoprotein particles (U snRNPs) have an essential role in the pre-mRNA processing, particularly in splicing, catalyzed by spliceosomes, large RNA-protein complexes composed of various snRNPs. Even though they are well defined in mammals, snRNPs are still not totally characterized in certain trypanosomatids as Trypanosoma cruzi. For this reason we subjected snRNAs (U2, U4, U5, and U6) from T. cruzi epimastigotes to molecular characterization by polymerase chain reaction (PCR) and reverse transcription-PCR. These amplified sequences were cloned, sequenced, and compared with those other of trypanosomatids. Among these snRNAs, U5 was less conserved and U6 the most conserved. Their respective secondary structures were predicted and compared with known T. brucei structures. In addition, the copy number of each snRNA in the T. cruzi genome was characterized by Southern blotting.

Biofilm formation at the solid-liquid and air-liquid interfaces by Acinetobacter species

The members of the genus Acinetobacter are Gram-negative cocobacilli that are frequently found in the environment but also in the hospital setting where they have been associated with outbreaks of nosocomial infections. Among them, Acinetobacter baumannii has emerged as the most common pathogenic species involved in hospital-acquired infections. One reason for this emergence may be its persistence in the hospital wards, in particular in the intensive care unit; this persistence could be partially explained by the capacity of these microorganisms to form biofilm. Therefore, our main objective was to study the prevalence of the two main types of biofilm formed by the most relevant Acinetobacter species, comparing biofilm formation between the different species. Findings: Biofilm formation at the air-liquid and solid-liquid interfaces was investigated in different Acinetobacter spp. and it appeared to be generally more important at 25°C than at 37°C. The biofilm formation at the solid-liquid interface by the members of the ACB-complex was at least 3 times higher than the other species (80-91% versus 5-24%). In addition, only the isolates belonging to this complex were able to form biofilm at the air-liquid interface; between 9% and 36% of the tested isolates formed this type of pellicle. Finally, within the ACB-complex, the biofilm formed at the air-liquid interface was almost 4 times higher for A. baumannii and Acinetobacter G13TU than for Acinetobacter G3 (36%, 27% & 9% respectively). Conclusions: Overall, this study has shown the capacity of the Acinetobacter spp to form two different types of biofilm: solid-liquid and air-liquid interfaces. This ability was generally higher at 25°C which might contribute to their persistence in the inanimate hospital environment. Our work has also demonstrated for the first time the ability of the members of the ACB-complex to form biofilm at the air-liquid interface, a feature that was not observed in other Acinetobacter species.

The Network Company in Catalonia : ICT, Productivity, Competitiveness, Salaries and Performance in Catalonia's Companies. Research report (synthesis document)

Resum en anglès del projecte de recerca L'empresa xarxa a Catalunya. TIC, productivitat, competitivitat, salaris i beneficis a l'empresa catalana té com a objectiu principal constatar que la consolidació d'un nou model estratègic, organitzatiu i d'activitat empresarial, vinculat amb la inversió i l'ús de les TIC (o empresa xarxa), modifica substancialment els patrons de comportament dels resultats empresarials, en especial la productivitat, la competitivitat, les retribucions dels treballadors i el benefici. La contrastació empírica de les hipòtesis de treball l'hem feta per mitjà de les dades d'una enquesta a una mostra representativa de 2.038 empreses catalanes. Amb la perspectiva de l'impacte de la inversió i l'ús de les TIC no s'aprecia una relació directa entre els processos d'innovació digital i els resultats de l'activitat de l'empresa catalana. En aquest sentit, hem hagut de segmentar el teixit productiu català per a buscar les organitzacions en què el procés de coinnovació tecnològica digital i organitzativa és més present i en què la intensitat de l'ús del coneixement és un recurs molt freqüent per a poder copsar impactes rellevants en els principals resultats empresarials. Això és així perquè l'economia catalana, avui, presenta una estructura productiva dual.

Concentrations of resveratrol and derivatives in foods and estimation of dietary intake in a Spanish population: European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort

Resveratrol has been shown to have beneficial effects on diseases related to oxidant and/or inflammatory processes and extends the lifespan of simple organisms including rodents. The objective of the present study was to estimate the dietary intake of resveratrol and piceid (R&P) present in foods, and to identify the principal dietary sources of these compounds in the Spanish adult population. For this purpose, a food composition database (FCDB) of R&P in Spanish foods was compiled. The study included 40 685 subjects aged 35–64 years from northern and southern regions of Spain who were included in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort. Usual food intake was assessed by personal interviews using a computerised version of a validated diet history method. An FCDB with 160 items was compiled. The estimated median and mean of R&P intake were 100 and 933 μg/d respectively. Approximately, 32 % of the population did not consume R&P. The most abundant of the four stilbenes studied was trans-piceid (53·6 %), followed by trans-resveratrol (20·9 %), cis-piceid (19·3 %) and cis-resveratrol (6·2 %). The most important source of R&P was wines (98·4 %) and grape and grape juices (1·6 %), whereas peanuts, pistachios and berries contributed to less than 0·01 %. For this reason the pattern of intake of R&P was similar to the wine pattern. This is the first time that R&P intake has been estimated in a Mediterranean country.

Risk of falls and bleeding in elderly patients with acute venous thromboembolism.

OBJECTIVE: Whether or not a high risk of falls increases the risk of bleeding in patients receiving anticoagulants remains a matter of debate. METHODS: We conducted a prospective cohort study involving 991 patients ≥65 years of age who received anticoagulants for acute venous thromboembolism (VTE) at nine Swiss hospitals between September 2009 and September 2012. The study outcomes were as follows: the time to a first major episode of bleeding; and clinically relevant nonmajor bleeding. We determined the associations between the risk of falls and the time to a first episode of bleeding using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. RESULTS: Four hundred fifty-eight of 991 patients (46%) were at high risk of falls. The mean duration of follow-up was 16.7 months. Patients at high risk of falls had a higher incidence of major bleeding (9.6 vs. 6.6 events/100 patient-years; P = 0.05) and a significantly higher incidence of clinically relevant nonmajor bleeding (16.7 vs. 8.3 events/100 patient-years; P < 0.001) than patients at low risk of falls. After adjustment, a high risk of falls was associated with clinically relevant nonmajor bleeding [subhazard ratio (SHR) = 1.74, 95% confidence interval (CI) = 1.23-2.46], but not with major bleeding (SHR = 1.24, 95% CI = 0.83-1.86). CONCLUSION: In elderly patients who receive anticoagulants because of VTE, a high risk of falls is significantly associated with clinically relevant nonmajor bleeding, but not with major bleeding. Whether or not a high risk of falls is a reason against providing anticoagulation beyond 3 months should be based on patient preferences and the risk of VTE recurrence.

Postpartum changes in plasma viral load and CD4 percentage among HIV-infected women from Latin American and Caribbean countries: the NISDI Perinatal Study

The goal of this study was to evaluate changes in plasma human immunodeficiency virus (HIV) RNA concentration [viral load (VL)] and CD4+ percentage (CD4%) during 6-12 weeks postpartum (PP) among HIV-infected women and to assess differences according to the reason for receipt of antiretrovirals (ARVs) during pregnancy [prophylaxis (PR) vs. treatment (TR)]. Data from a prospective cohort of HIV-infected pregnant women (National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study) were analyzed. Women experiencing their first pregnancy who received ARVs for PR (started during pregnancy, stopped PP) or for TR (initiated prior to pregnancy and/or continued PP) were included and were followed PP. Increases in plasma VL (> 0.5 log10) and decreases in CD4% (> 20% relative decrease in CD4%) between hospital discharge (HD) and PP were assessed. Of the 1,229 women enrolled, 1,119 met the inclusion criteria (PR: 601; TR: 518). At enrollment, 87% were asymptomatic. The median CD4% values were: HD [34% (PR); 25% (TR)] and PP [29% (PR); 24% (TR)]. The VL increases were 60% (PR) and 19% (TR) (p < 0.0001). The CD4% decreases were 36% (PR) and 18% (TR) (p < 0.0001). Women receiving PR were more likely to exhibit an increase in VL [adjusted odds ratio (AOR) 7.7 (95% CI: 5.5-10.9) and a CD4% decrease (AOR 2.3; 95% CI: 1.6-3.2). Women receiving PR are more likely to have VL increases and CD4% decreases compared to those receiving TR. The clinical implications of these VL and CD4% changes remain to be explored.

Biofilm formation at the solid-liquid and air-liquid interfaces by Acinetobacter species.

BACKGROUND The members of the genus Acinetobacter are Gram-negative cocobacilli that are frequently found in the environment but also in the hospital setting where they have been associated with outbreaks of nosocomial infections. Among them, Acinetobacter baumannii has emerged as the most common pathogenic species involved in hospital-acquired infections. One reason for this emergence may be its persistence in the hospital wards, in particular in the intensive care unit; this persistence could be partially explained by the capacity of these microorganisms to form biofilm. Therefore, our main objective was to study the prevalence of the two main types of biofilm formed by the most relevant Acinetobacter species, comparing biofilm formation between the different species. FINDINGS Biofilm formation at the air-liquid and solid-liquid interfaces was investigated in different Acinetobacter spp. and it appeared to be generally more important at 25°C than at 37°C. The biofilm formation at the solid-liquid interface by the members of the ACB-complex was at least 3 times higher than the other species (80-91% versus 5-24%). In addition, only the isolates belonging to this complex were able to form biofilm at the air-liquid interface; between 9% and 36% of the tested isolates formed this type of pellicle. Finally, within the ACB-complex, the biofilm formed at the air-liquid interface was almost 4 times higher for A. baumannii and Acinetobacter G13TU than for Acinetobacter G3 (36%, 27% & 9% respectively). CONCLUSIONS Overall, this study has shown the capacity of the Acinetobacter spp to form two different types of biofilm: solid-liquid and air-liquid interfaces. This ability was generally higher at 25°C which might contribute to their persistence in the inanimate hospital environment. Our work has also demonstrated for the first time the ability of the members of the ACB-complex to form biofilm at the air-liquid interface, a feature that was not observed in other Acinetobacter species.

Long-term efficacy and safety of atazanavir/ritonavir treatment in a cohort of treatment-naïve HIV patients: An interim analysis of the REMAIN study.

Purpose: Combined antiretroviral therapy has dramatically improved HIV-infected individuals survival. Long-term strategies are currently needed to achieve the goal of durable virologic suppression. However, long-term available data for specific antiretrovirals (ARV) are limited. In clinical trials, boosted atazanavir (ATV/r) regimens has shown good efficacy and tolerability in ARV-naïve patients for up to 4 years. The REMAIN study aimed to evaluate the long-term outcomes of ATV/r regimens in ARV-naïve patients in a real life setting. Methods: Non-comparative, observational study conducted in Germany, Portugal and Spain. Historical and longitudinal follow-up data was extracted six monthly from the medical record of HIV-infected, treatment-naïve patients, who initiated an ATV/r-regimen between 2008 and 2010. The primary endpoint was the proportion of patients remaining on ATV treatment over time. Secondary endpoints included virologic response (HIV-1 RNA <50 c/mL and <500 c/mL), reasons for discontinuation and long-term safety. The duration of treatment and time to virologic failure (VF) were analyzed using the Kaplan- Meier method. Data from an interim analysis including patients with at least one year of follow-up are reported here. Results: A total of 411 patients were included in this interim analysis [median (Q1, Q3) follow-up: 23.42 (16.25, 32.24) months≥: 77% male; median age 40 years [min, max: 19, 78≥; 16% IDUs; 18% CDC C; 18% hepatitis C. TDF/FTC was the most common backbone (85%). At baseline, median (Q1, Q3) HIV-RNA and CD4 cell count were 4.91 (4.34, 5.34) log10 c/mL and 256 (139, 353) cells/mm3, respectively. The probability of remaining on treatment was 0.84 (95% CI: 0.80, 0.87) and 0.72 (95% CI: 0.67, 0.76) for the first and second year, respectively. After 2 years of follow-up, 84% (95% CI: 0.79, 0.88) of patients were virologically suppressed (<50 c/mL). No major protease inhibitors mutations were observed at VF. Overall, 125 patients (30%) discontinued ATV therapy [median (Q1, Q3) time to discontinuation: 11.14 (6.24, 19.35) months]. Adverse events (AEs) were the main reason for discontinuation (n =47, 11%). Hyperbilirubinaemia was the most common AE leading to discontinuation (14 patients). No unexpected AEs were reported. Conclusions: In a real life clinical setting, ATV/r regimens showed durable virologic efficacy with good tolerability in an ARV-naïve population. Data from longer follow-up will provide additional valuable information.

Study and implementation of some quantitative trading models

Quantitative or algorithmic trading is the automatization of investments decisions obeying a fixed or dynamic sets of rules to determine trading orders. It has increasingly made its way up to 70% of the trading volume of one of the biggest financial markets such as the New York Stock Exchange (NYSE). However, there is not a signi cant amount of academic literature devoted to it due to the private nature of investment banks and hedge funds. This projects aims to review the literature and discuss the models available in a subject that publications are scarce and infrequently. We review the basic and fundamental mathematical concepts needed for modeling financial markets such as: stochastic processes, stochastic integration and basic models for prices and spreads dynamics necessary for building quantitative strategies. We also contrast these models with real market data with minutely sampling frequency from the Dow Jones Industrial Average (DJIA). Quantitative strategies try to exploit two types of behavior: trend following or mean reversion. The former is grouped in the so-called technical models and the later in the so-called pairs trading. Technical models have been discarded by financial theoreticians but we show that they can be properly cast into a well defined scientific predictor if the signal generated by them pass the test of being a Markov time. That is, we can tell if the signal has occurred or not by examining the information up to the current time; or more technically, if the event is F_t-measurable. On the other hand the concept of pairs trading or market neutral strategy is fairly simple. However it can be cast in a variety of mathematical models ranging from a method based on a simple euclidean distance, in a co-integration framework or involving stochastic differential equations such as the well-known Ornstein-Uhlenbeck mean reversal ODE and its variations. A model for forecasting any economic or financial magnitude could be properly defined with scientific rigor but it could also lack of any economical value and be considered useless from a practical point of view. This is why this project could not be complete without a backtesting of the mentioned strategies. Conducting a useful and realistic backtesting is by no means a trivial exercise since the \laws" that govern financial markets are constantly evolving in time. This is the reason because we make emphasis in the calibration process of the strategies' parameters to adapt the given market conditions. We find out that the parameters from technical models are more volatile than their counterpart form market neutral strategies and calibration must be done in a high-frequency sampling manner to constantly track the currently market situation. As a whole, the goal of this project is to provide an overview of a quantitative approach to investment reviewing basic strategies and illustrating them by means of a back-testing with real financial market data. The sources of the data used in this project are Bloomberg for intraday time series and Yahoo! for daily prices. All numeric computations and graphics used and shown in this project were implemented in MATLAB^R scratch from scratch as a part of this thesis. No other mathematical or statistical software was used.

Accuracy of mucocutaneous leishmaniasis diagnosis using polymerase chain reaction: systematic literature review and meta-analysis

The diagnosis of mucocutaneous leishmaniasis (MCL) is hampered by the absence of a gold standard. An accurate diagnosis is essential because of the high toxicity of the medications for the disease. This study aimed to assess the ability of polymerase chain reaction (PCR) to identify MCL and to compare these results with clinical research recently published by the authors. A systematic literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA Statement was performed using comprehensive search criteria and communication with the authors. A meta-analysis considering the estimates of the univariate and bivariate models was performed. Specificity near 100% was common among the papers. The primary reason for accuracy differences was sensitivity. The meta-analysis, which was only possible for PCR samples of lesion fragments, revealed a sensitivity of 71% [95% confidence interval (CI) = 0.59; 0.81] and a specificity of 93% (95% CI = 0.83; 0.98) in the bivariate model. The search for measures that could increase the sensitivity of PCR should be encouraged. The quality of the collected material and the optimisation of the amplification of genetic material should be prioritised.

Appropriate therapy for fistulizing and fibrostenotic Crohn's disease: results of a multidisciplinary expert panel - EPACT II

Introduction: Many therapeutic decisions in the management of fistulizing and fibrostenotic Crohn's disease (CD) have to be taken without the benefit of strong scientific evidence. For this reason, explicit appropriateness criteria for CD fistula and stenosis treatment were developed by a multidisciplinary European expert panel in 2004 with the aim of making them easily available on the Internet and thus allowing individual case scenario evaluation; these criteria were updated in 2007. Methods: Twelve international experts convened in Geneva, Switzerland in December 2007. Explicit clinical scenarios, corresponding to real daily practice, were rated on a 9-point scale based on evidence from the published literature and panelists' own expertise. Median ratings were stratified into three categories: appropriate (7-9), uncertain (4-6) and inappropriate (1-3). Results: Overall, panelists rated 60 indications pertaining to fistulas. Antibiotics, azathioprine/6-mercaptopurine and conservative surgery are the mainstay of therapy for simple and complex fistulas. In the event of previous failure of azathioprine/6-mercaptopurine therapy, methotrexate and infliximab were considered appropriate for complex fistulas. The panel also rated 72 indications related to the management of fibrostenotic CD. The experts considered balloon dilation, if the stricture was endoscopically accessible, stricturoplasty and bowel resection to be appropriate for small bowel fibrostenotic Crohn's disease, and balloon dilation and bowel resection appropriate for fibrostenotic colonic disease. In the presence of an ileocolonic or ileorectal anastomotic stricture of <7 cm, endoscopic balloon dilation, and bowel resection were considered appropriate. Conclusion: Antibiotics, azathioprine/6-mercaptopurine, and conservative surgery are the mainstay of therapy for fistulizing Crohn's disease. Infliximab is a therapeutic option in patients without prior response to immunosuppressant therapy. In fibrostenotic Crohn's disease, endoscopic balloon dilation, if feasible, or surgical therapy should be considered. These expert recommendations are available online (www.epact.ch). Prospective evaluation is now needed to test the validity of these appropriateness criteria in clinical practice. (C) 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.