Argemone mexicana decoction versus artesunate-amodiaquine for the management of malaria in Mali: policy and public-health implications.

A classic way of delaying drug resistance is to use an alternative when possible. We tested the malaria treatment Argemone mexicana decoction (AM), a validated self-prepared traditional medicine made with one widely available plant and safe across wide dose variations. In an attempt to reflect the real situation in the home-based management of malaria in a remote Malian village, 301 patients with presumed uncomplicated malaria (median age 5 years) were randomly assigned to receive AM or artesunate-amodiaquine [artemisinin combination therapy (ACT)] as first-line treatment. Both treatments were well tolerated. Over 28 days, second-line treatment was not required for 89% (95% CI 84.1-93.2) of patients on AM, versus 95% (95% CI 88.8-98.3) on ACT. Deterioration to severe malaria was 1.9% in both groups in children aged </=5 years (there were no cases in patients aged >5 years) and 0% had coma/convulsions. AM, now government-approved in Mali, could be tested as a first-line complement to standard modern drugs in high-transmission areas, in order to reduce the drug pressure for development of resistance to ACT, in the management of malaria. In view of the low rate of severe malaria and good tolerability, AM may also constitute a first-aid treatment when access to other antimalarials is delayed.

Challenging the "inoffensiveness" of regular cannabis use by its associations with other current risky substance use--a census of 20-year-old Swiss men.

3,537 men enrolling in 2007 for mandatory army recruitment procedures were assessed for the co-occurrence of risky licit substance use among risky cannabis users. Risky cannabis use was defined as at least twice weekly; risky alcohol use as 6+ drinks more than once/monthly, or more than 20 drinks per week; and risky tobacco use as daily smoking. Ninety-five percent of all risky cannabis users reported other risky use. They began using cannabis earlier than did non-risky users, but age of onset was unrelated to other risky substance use. A pressing public health issue among cannabis users stems from risky licit substance use warranting preventive efforts within this age group.

Les principes infallibles et les regles asurées de la iuste prononciacion de nôtre langue : ouvrage d'une recherche toute particulière, nécêsere à tous les étrangers, et à ceux qui parlent en public ([Reprod.]) / par le sieur L. [Lartigaut]

Collection : Archives de la linguistique française ; 227

The use of positional scanning synthetic combinatorial libraries (PS-SCL) to study T Lympohcyte specificity and degeneracy

Les cellules CD8? T cytolytiques (CTL) sont les principaux effecteurs du système immunitaire adaptatif contre les infections et les tumeurs. La récente identification d?antigènes tumoraux humains reconnus par des cellules T cytolytiques est la base pour le, développement des vaccins antigène spécifiques contre le cancer. Le nombre d?antigènes tumoraux reconnus par des CTL que puisse être utilisé comme cible pour la vaccination des patients atteints du cancer est encore limité. Une nouvelle technique, simple et rapide, vient d?être proposée pour l?identification d?antigènes reconnus par des CTL. Elle se base sur l?utilisation de librairies combinatoriales de peptides arrangées en un format de "scanning" ou balayage par position (PS-SCL). La première partie de cette étude a consisté à valider cette nouvelle technique par une analyse détaillée de la reconnaissance des PS-SCL par différents clones de CTL spécifiques pour des antigènes associés à la tumeur (TAA) connus ainsi que par des clones de spécificité inconnue. Les résultats de ces analyses révèlent que pour tous les clones, la plupart des acides aminés qui composent la séquence du peptide antigénique naturel ont été identifiés par l?utilisation des PS-SCL. Les résultats obtenus ont permis d?identifier des peptides analogues ayant une antigènicité augmentée par rapport au peptide naturel, ainsi que des peptides comportant de multiples modifications de séquence, mais présentant la même réactivité que le peptide naturel. La deuxième partie de cette étude a consisté à effectuer des analyses biométriques des résultats complexes générés par la PS-SCL. Cette approche a permis l?identification des séquences correspondant aux épitopes naturels à partir de bases de données de peptides publiques. Parmi des milliers de peptides, les séquences naturelles se trouvent comprises dans les 30 séquences ayant les scores potentiels de stimulation les plus élevés pour chaque TAA étudié. Mais plus important encore, l?utilisation des PS-SCL avec un clone réactif contre des cellules tumorales mais de spécificité inconnue nous a permis d?identifier I?epitope reconnu par ce clone. Les données présentées ici encouragent l?utilisation des PS-SCL pour l?identification et l?optimisation d?épitopes pour des CTL réactifs anti-tumoraux, ainsi que pour l?étude de la reconnaissance dégénérée d?antigènes par les CTL.<br/><br/>CD8+ cytolytic T lymphocytes (CTL) are the main effector cells of the adaptive immune system against infection and tumors. The recent identification of moleculariy defined human tumor Ags recognized by autologous CTL has opened new opportunities for the development of Ag-specific cancer vaccines. Despite extensive work, however, the number of CTL-defined tumor Ags that are suitable targets for the vaccination of cancer patients is still limited, especially because of the laborious and time consuming nature of the procedures currentiy used for their identification. The use of combinatorial peptide libraries in positionai scanning format (Positional Scanning Synthetic Combinatorial Libraries, PS-SCL)' has recently been proposed as an alternative approach for the identification of these epitopes. To validate this approach, we analyzed in detail the recognition of PS-SCL by tumor-reactive CTL clones specific for multiple well-defined tumor-associated Ags (TAA) as well as by tumor-reactive CTL clones of unknown specificity. The results of these analyses revealed that for all the TAA-specific clones studied most of the amino acids composing the native antigenic peptide sequences could be identified through the use of PS-SCL. Based on the data obtained from the screening of PS-SCL, we could design peptide analogs of increased antigenicity as well as cross-reactive analog peptides containing multiple amino acid substitutions. In addition, the resuits of PS-SCL-screening combined with a recently developed biometric data analysis (PS-SCL-based biometric database analysis) allowed the identification of the native peptides in public protein databases among the 30 most active sequences, and this was the case for all the TAA studied. More importantiy, the screening of PS- SCL with a tumor-reactive CTL clone of unknown specificity resulted in the identification of the actual epitope. Overall, these data encourage the use of PS-SCL not oniy for the identification and optimization of tumor-associated CTL epitopes, but also for the analysis of degeneracy in T lymphocyte receptor (TCR) recognition of tumor Ags.<br/><br/>Les cellules T CD8? cytolytiques font partie des globules blancs du sang et sont les principales responsables de la lutte contre les infections et les tumeurs. Les immunologistes cherchent depuis des années à identifier des molécules exprimées et présentées à la surface des tumeurs qui puissent être reconnues par des cellules T CD8? cytolytiques capables ensuite de tuer ces tumeurs de façon spécifique. Ce type de molécules représente la base pour le développement de vaccins contre le cancer puisqu?elles pourraient être injectées aux patients afin d?induire une réponse anti- tumorale. A présent, il y a très peu de molécules capables de stimuler le système immunitaire contre les tumeurs qui sont connues parce que les techniques développées à ce jour pour leur identification sont complexes et longues. Une nouvelle technique vient d?être proposée pour l?identification de ce type de molécules qui se base sur l?utilisation de librairies de peptides. Ces librairies représentent toutes les combinaisons possibles des composants de base des molécules recherchées. La première partie de cette étude a consisté à valider cette nouvelle technique en utilisant des cellules T CD8? cytolytiques capables de tuer des cellules tumorales en reconnaissant une molécule connue présente à leur surface. On a démontré que l?utilisation des librairies permet d?identifier la plupart des composants de base de la molécule reconnue par les cellules T CD8? cytolytiques utilisées. La deuxième partie de cette étude a consisté à effectuer une recherche des molécules potentiellement actives dans des protéines présentes dans des bases des données en utilisant un programme informatique qui permet de classer les molécules sur la base de leur activité biologique. Parmi des milliers de molécules de la base de données, celles reconnues par nos cellules T CD8? cytolytiques ont été trouvées parmi les plus actives. Plus intéressant encore, la combinaison de ces deux techniques nous a permis d?identifier la molécule reconnue par une population de cellules T CD8? cytolytiques ayant une activité anti-tumorale, mais pour laquelle on ne connaissait pas la spécificité. Nos résultats encouragent l?utilisation des librairies pour trouver et optimiser des molécules reconnues spécifiquement par des cellules T CD8? cytolytiques capables de tuer des tumeurs.

Uses of cancer registries for public health and clinical research in Europe : results of the European Network of Cancer Registries survey among 161 population-based cancer registries during 2010-2012

AIM: To provide insight into cancer registration coverage, data access and use in Europe. This contributes to data and infrastructure harmonisation and will foster a more prominent role of cancer registries (CRs) within public health, clinical policy and cancer research, whether within or outside the European Research Area. METHODS: During 2010-12 an extensive survey of cancer registration practices and data use was conducted among 161 population-based CRs across Europe. Responding registries (66%) operated in 33 countries, including 23 with national coverage. RESULTS: Population-based oncological surveillance started during the 1940-50s in the northwest of Europe and from the 1970s to 1990s in other regions. The European Union (EU) protection regulations affected data access, especially in Germany and France, but less in the Netherlands or Belgium. Regular reports were produced by CRs on incidence rates (95%), survival (60%) and stage for selected tumours (80%). Evaluation of cancer control and quality of care remained modest except in a few dedicated CRs. Variables evaluated were support of clinical audits, monitoring adherence to clinical guidelines, improvement of cancer care and evaluation of mass cancer screening. Evaluation of diagnostic imaging tools was only occasional. CONCLUSION: Most population-based CRs are well equipped for strengthening cancer surveillance across Europe. Data quality and intensity of use depend on the role the cancer registry plays in the politico, oncomedical and public health setting within the country. Standard registration methodology could therefore not be translated to equivalent advances in cancer prevention and mass screening, quality of care, translational research of prognosis and survivorship across Europe. Further European collaboration remains essential to ensure access to data and comparability of the results.

Experts' consensus on use of electronic cigarettes: a Delphi survey from Switzerland.

OBJECTIVES: In some countries, nicotine-containing electronic cigarettes (e-cigarettes) are considered a consumer product without specific regulations. In others (eg, Switzerland), the sale of e-cigarettes containing nicotine is forbidden, despite the eagerness of many smokers to obtain them. As scientific data about efficacy and long-term safety of these products are scarce, tobacco control experts are divided on how to regulate them. In order to gain consensus among experts to provide recommendations to health authorities, we performed a national consensus study. SETTING: We used a Delphi method with electronic questionnaires to bring together the opinion of Swiss experts on e-cigarettes. PARTICIPANTS: 40 Swiss experts from across the country. OUTCOME MEASURES: We measured the degree of consensus between experts on recommendations regarding regulation, sale, use of and general opinion about e-cigarettes containing nicotine. New recommendations and statements were added following the experts' answers and comments. RESULTS: There was consensus that e-cigarettes containing nicotine should be made available, but only under specific conditions. Sale should be restricted to adults, using quality standards, a maximum level of nicotine and with an accompanying list of authorised ingredients. Advertisement should be restricted and use in public places should be forbidden. CONCLUSIONS: These recommendations encompass three principles: (1) the reality principle, as the product is already on the market; (2) the prevention principle, as e-cigarettes provide an alternative to tobacco for actual smokers, and (3) the precautionary principle, to protect minors and non-smokers, since long-term effects are not yet known. Swiss authorities should design specific regulations to sell nicotine-containing e-cigarettes.

Cardiovascular disease and the changing face of global public health : a focus on low and middle income countries

Eighty percent of the global 17 million deaths due to cardiovascular disease (CVD) occur in low and middle income countries (LMICs). The burden of CVD and other noncommunicable diseases (NCDs) is expected to markedly increase because of the global aging of the population and increasing exposure to detrimental lifestyle-related risk in LMICs. Interventions to reduce four main risks related to modifiable behaviors (tobacco use, unhealthy diet, low physical activity and excess alcohol consumption) are key elements for effective primary prevention of the four main NCDs (CVD, cancer, diabetes and chronic pulmonary disease). These behaviors are best improved through structural interventions (e.g., clean air policy, taxes on cigarettes, new recipes for processed foods with reduced salt and fat, urban shaping to improve mobility, etc.). In addition, health systems in LMICs should be reoriented to deliver integrated cost-effective treatment to persons at high risk at the primary health care level. The full implementation of a small number of highly cost effective, affordable and scalable interventions ("best buys") is likely to be the necessary and sufficient ingredient for curbing NCDs in LMICs. NCDs are both a cause and a consequence of poverty. It is therefore important to frame NCD prevention and control within the broader context of social determinants and development agenda. The recent emphasis on NCDs at a number of health and economic forums (including the September 2011 High Level Meeting on NCDs at the United Nations) provides a new opportunity to move the NCD agenda forward in LMICs.

Use and perception of urban green spaces in Barcelona

Background: Although the mechanisms are not well understood yet, evidence exists of the benefits of urban green spaces for human health. As a consequence, one of the concerns of public health interventions must be to promote the use of urban green spaces within cities. Aims: This study aims to explore the citizens’ purposes of use of urban green spaces as well as the elements related to the characteristics of these places that condition their use. Methods: In-depth interviews were conducted with non-hospitalised people living in different areas of Barcelona, with different socioeconomic status and different residential distance to urban green spaces (n = 20). Thematic content analysis of the qualitative data was performed. Results: Physical pursuits and attention restoration were identified as prominent purposes of use of urban green spaces. The natural features of urban green spaces were identified as the most relevant determiners for the use of these places. Conclusions: To promote the use of urban green spaces, qualitative findings from this study suggest that purpose-built places should be provided. Moreover, natural features of urban green spaces must be particularly taken into account when designing and maintaining them.

Use of alternative and complementary therapies in labor and delivery care: a cross-sectional study of midwives" training in Catalan hospitals accredited as centers for normal birth

Background: The use of complementary and alternative medicine (CAM) and complementary and alternative therapies (CAT) during pregnancy is increasing. Scientific evidence for CAM and CAT in the field of obstetrics mainly covers pain relief in labor. Midwives are responsible for labor and delivery care: hence, their knowledge of CAM and CAT is important. The aims of this study are to describe the professional profile of midwives who provide care for natural childbirth in Catalan hospitals accredited as centers for normal birth, to assess midwives" level of training in CAT and their use of these therapies, and to identify specific resources for CAT in labor wards. Methods: A descriptive, cross-sectional, quantitative method was used to assess the level of training and use of CAT by midwives working at 28 hospitals in Catalonia, Spain, accredited as public normal birth centers. Results: Just under a third of midwives (30.4%) trained in CAT after completion of basic training. They trained in an average of 5.97 therapies (SD 3.56). The number of CAT in which the midwives were trained correlated negatively with age (r = - 0.284; p < 0.001) and with their time working at the hospital in years (r = - 0.136; p = 0.036). Midwives trained in CAT considered that the following therapies were useful or very useful for pain relief during labor and delivery: relaxation techniques (64.3%), hydrotherapy (84.8%) and the application of compresses to the perineum (75.9%). The availability of resources for providing CAT during normal birth care varied widely from center to center. Conclusions: Age may influence attitudes towards training. It is important to increase the number of midwives trained in CAM for pain relief during childbirth, in order to promote the use of CAT and ensure efficiency and safety. CAT resources at accredited hospitals providing normal childbirth care should also be standardized.

Use of alternative and complementary therapies in labor and delivery care: a cross-sectional study of midwives" training in Catalan hospitals accredited as centers for normal birth

Background: The use of complementary and alternative medicine (CAM) and complementary and alternative therapies (CAT) during pregnancy is increasing. Scientific evidence for CAM and CAT in the field of obstetrics mainly covers pain relief in labor. Midwives are responsible for labor and delivery care: hence, their knowledge of CAM and CAT is important. The aims of this study are to describe the professional profile of midwives who provide care for natural childbirth in Catalan hospitals accredited as centers for normal birth, to assess midwives" level of training in CAT and their use of these therapies, and to identify specific resources for CAT in labor wards. Methods: A descriptive, cross-sectional, quantitative method was used to assess the level of training and use of CAT by midwives working at 28 hospitals in Catalonia, Spain, accredited as public normal birth centers. Results: Just under a third of midwives (30.4%) trained in CAT after completion of basic training. They trained in an average of 5.97 therapies (SD 3.56). The number of CAT in which the midwives were trained correlated negatively with age (r = - 0.284; p < 0.001) and with their time working at the hospital in years (r = - 0.136; p = 0.036). Midwives trained in CAT considered that the following therapies were useful or very useful for pain relief during labor and delivery: relaxation techniques (64.3%), hydrotherapy (84.8%) and the application of compresses to the perineum (75.9%). The availability of resources for providing CAT during normal birth care varied widely from center to center. Conclusions: Age may influence attitudes towards training. It is important to increase the number of midwives trained in CAM for pain relief during childbirth, in order to promote the use of CAT and ensure efficiency and safety. CAT resources at accredited hospitals providing normal childbirth care should also be standardized.

Cannabis use and other predictors of the onset of daily cigarette use in young men: what matters most? Results from a longitudinal study.

BACKGROUND: According to the gateway hypothesis, tobacco use is a gateway of cannabis use. However, there is increasing evidence that cannabis use also predicts the progression of tobacco use (reverse gateway hypothesis). Unfortunately, the importance of cannabis use compared to other predictors of tobacco use is less clear. The aim of this study was to examine which variables, in addition to cannabis use, best predict the onset of daily cigarette smoking in young men. METHODS: A total of 5,590 young Swiss men (mean age = 19.4 years, SD = 1.2) provided data on their substance use, socio-demographic background, religion, health, social context, and personality at baseline and after 18 months. We modelled the predictors of progression to daily cigarette smoking using logistic regression analyses (n = 4,230). RESULTS: In the multivariate overall model, use of cannabis remained among the strongest predictors for the onset of daily cigarette use. Daily cigarette use was also predicted by a lifetime use of at least 50 cigarettes, occasional cigarette use, educational level, religious affiliation, parental situation, peers with psychiatric problems, and sociability. CONCLUSIONS: Our results highlight the relevance of cannabis use compared to other potential predictors of the progression of tobacco use and thereby support the reverse gateway hypothesis.

E-Cigarettes: A Review of New Trends in Cannabis Use.

The emergence of electronic cigarettes (e-cigs) has given cannabis smokers a new method of inhaling cannabinoids. E-cigs differ from traditional marijuana cigarettes in several respects. First, it is assumed that vaporizing cannabinoids at lower temperatures is safer because it produces smaller amounts of toxic substances than the hot combustion of a marijuana cigarette. Recreational cannabis users can discretely "vape" deodorized cannabis extracts with minimal annoyance to the people around them and less chance of detection. There are nevertheless several drawbacks worth mentioning: although manufacturing commercial (or homemade) cannabinoid-enriched electronic liquids (e-liquids) requires lengthy, complex processing, some are readily on the Internet despite their lack of quality control, expiry date, and conditions of preservation and, above all, any toxicological and clinical assessment. Besides these safety problems, the regulatory situation surrounding e-liquids is often unclear. More simply ground cannabis flowering heads or concentrated, oily THC extracts (such as butane honey oil or BHO) can be vaped in specially designed, pen-sized marijuana vaporizers. Analysis of a commercial e-liquid rich in cannabidiol showed that it contained a smaller dose of active ingredient than advertised; testing our laboratory-made, purified BHO, however, confirmed that it could be vaped in an e-cig to deliver a psychoactive dose of THC. The health consequences specific to vaping these cannabis preparations remain largely unknown and speculative due to the absence of comprehensive, robust scientific studies. The most significant health concerns involve the vaping of cannabinoids by children and teenagers. E-cigs could provide an alternative gateway to cannabis use for young people. Furthermore, vaping cannabinoids could lead to environmental and passive contamination.

Predictors and Correlates of Substance Use among Young Men. The Longitudinal “From a Boy to a Man” Birth Cohort Study.

Substance use is one of our most important public health problems. Studying risk factors in a longitudinal study setting helps to identify subgroups of young people at greater risk for substance-use-related problems, and to facilitate targeted prevention efforts. The aim of this thesis was to study childhood predictors and correlates of substance-use-related outcomes among young men in a longitudinal, nationwide birth cohort study. The study population included 10% of all Finnish-speaking boys born in Finland in 1981 (n=2946, 97% of the target population). In 1989, at age eight, valid measures of psychiatric symptoms (Rutter questionnaires and Children’s Depression Inventory) were obtained from parents, teachers and the boys themselves. In 1999, at age 18, boys were reached at their obligatory military call-up (n=2348, 80% of the boys attending the study in 1989). Self-reports of substance use, psychopathology, adaptive functioning (Young Adult Self-Report), and mental health service use were obtained through questionnaires. Information about psychiatric diagnoses from the Military Register (age 18-23 years) and information about offending from the National Police Register (age 16-20 years) were collected in early adulthood (92% of the 1989sample). Boys with childhood conduct, hyperactive, and comorbid conduct-emotional problems had elevated rates of substance use and substance-use-related crime in early adulthood. Depressive symptoms predicted daily smoking, especially among boys of low-educated fathers. Emotional problems predicted lower occurrence of drunkenness-related alcohol use and smoking. Teacher reports on boys’ problem behaviour had the best predictive power for later substance use. At age 18, frequent drunkenness associated with delinquency, smoking and illicit drug use, and having friends. Occasional drunkenness associated with better psychosocial functioning in general compared to boys with frequent drunkenness or without drunkenness-related alcohol use. Illicit drug use without drug offending was not predicted by childhood psychiatric symptoms, but 22% of boys with illicit drug use had a psychiatric diagnosis in early adulthood. Drug offenders, in turn, had psychiatric problems both in childhood and in adulthood. Psychiatric disorders were common among young men with substance-use-related crime. Recidivist crime associated strongly with having a substance use disorder diagnosis according to the Military Register. At age 18, frequent drunkenness was common among boys entering mental health services, but entering substance use treatment was non-existent. According to the findings of this thesis, substance-use-related outcomes accumulate in boys having psychiatric problems both in childhood and in early adulthood. Targeted early interventions in school health care systems, particularly for boys with childhood hyperactive, conduct, and comorbid conduct-emotional problems are recommended. Psychiatric problems and risky behaviours, such as delinquency should always be assessed alongside substance use. Specialized and multidisciplinary care are required for young men who have multiple or complex needs, for instance, for young men with drug offending and recidivist crime. Integrating a substance use treatment perspective with other services where young men are encountered is emphasized.