Snus and Snuff Use in Switzerland Among Young Men: Are There Beneficial Effects on Smoking?

There are few recent longitudinal studies on smokeless tobacco (SLT) products and smoking outside the United States or European Nordic countries. The present longitudinal study tests whether Swedish-type snus and nasal snuff use decreases smoking incidence and prevalence in a central European country. The sample consisted of 5198 Swiss men (around 20 years of age). Retention rate was 91.5% over 15 months. Regression models, adjusting for a variety of psychosocial, smoking-related, and other risk factors, assessed whether no, low (less than weekly), and high (weekly or more) use baseline groups showed changes or maintenance in snus and snuff use related to smoking initiation, cessation, and reduction. Among baseline nonsmokers, snus initiators (OR = 1.90, p = .003) and low baseline maintainers (OR = 4.51, p < .001) were more likely to start smoking (reference: persistent nonusers of snus). Among baseline smokers, initiators (OR = 2.79, p < .001) and low baseline maintainers (OR = 2.71, p = .005) more often continued smoking, whereas snus quitters less frequently continued smoking (OR = 0.57, p = .009). High baseline maintainers were non-significantly less likely to continue smoking (OR = 0.71, p = .315). Among continuing smokers, only snus quitters significantly reduced the number of cigarettes smoked per day (b = -1.61, p = .002) compared with persistent nonusers of snus. Results were similar for snuff. SLT use did not have any significant beneficial effects on young men in Switzerland but significantly increased the likelihood of smoking initiation and continuation, independent of whether the substance is legally sold (snuff) or not (snus). This does not exclude that there may be beneficial effects at older ages. Our research provides evidence that SLT use has no benefits for cigarette smoking initiation, cessation, or reduction among young men in a central European country, where SLT is not highly promoted or receives tax incentives. This is true for both legally sold nasal snuff and Swedish-type snus that cannot be legally sold. Results indicate that without incentives for using it, among young people shifts from smoking to SLT use are questionable and confirms the need for country-specific studies before the global public health community engages in promoting SLT

Produtividade e valor nutritivo de pasto de capim-elefante manejado sob princípios agroecológicos.

Objetivou-se avaliar o valor nutritivo do capim-elefante, quanto aos teores de PB e FDN e a digestibilidade in vitro da MS (DIVMS), submetido a algumas práticas agroecológicas. Foram usados dois piquetes (0,15 ha cada), onde foi estabelecido o capim-elefante, em 2001, com espaçamento entrelinhas de três metros. Nas entrelinhas, estabeleceram-se aveia (Avena strigosa Schreb.) e azevém (Lolium multiflorum Lam.) no período hibernal e, no estival, permitiu-se o desenvolvimento de espécies de crescimento espontâneo. A adubação foi feita com fertilizantes orgânicos (150 kg de N /ha). No período experimental (24/04/2004 a 05/05/2005), foram conduzidos sete pastejos. Os animais experimentais foram vacas da raça Holandesa que receberam, como complementação alimentar, 3,5 kg/dia de concentrado. Avaliaram-se a massa de forragem inicial, composição botânica do pasto e os componentes estruturais. Para as análises de valor nutritivo do pasto, foram feitas amostragens simulando o pastejo. O delineamento experimental foi de blocos ao acaso com duas repetições (piquetes) e sete tratamentos (pastejos). Os melhores resultados do valor nutritivo foram obtidos no período hibernal. Foram encontradas correlações negativas da PB e DIVMS e positivas da FDN com a biomassa de lâminas foliares do capim-elefante. O capim-elefante, manejado sob princípios agroecológicos, apresentou alto valor nutritivo e produtividade, tanto no verão quanto no inverno, possibilitando que a produção animal seja mais sustentável no decorrer do ano

Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial

Background Cabotegravir and rilpivirine are antiretroviral drugs in development as long-acting injectable formulations. The LATTE-2 study evaluated long-acting cabotegravir plus rilpivirine for maintenance of HIV-1 viral suppression through 96 weeks. Methods In this randomised, phase 2b, open-label study, treatment-naive adults infected with HIV-1 initially received oral cabotegravir 30 mg plus abacavir–lamivudine 600–300 mg once daily. The objective of this study was to select an intramuscular dosing regimen based on a comparison of the antiviral activity, tolerability, and safety of the two intramuscular dosing regimens relative to oral cabotegravir plus abacavir–lamivudine. After a 20-week induction period on oral cabotegravir plus abacavir–lamivudine, patients with viral suppression (plasma HIV-1 RNA 90%). Difference in proportions and associated 95% CIs were supportive to the primary analysis. The trial is registered at ClinicalTrials.gov, number NCT02120352. Findings Among 309 enrolled patients, 286 were randomly assigned to the maintenance period (115 to each of the 4-week and 8-week groups and 56 to the oral treatment group). This study is currently ongoing. At 32 weeks following randomisation, both long-acting regimens met primary criteria for comparability in viral suppression relative to the oral comparator group. Viral suppression was maintained at 32 weeks in 51 (91%) of 56 patients in the oral treatment group, 108 (94%) of 115 patients in the 4-week group (difference 2·8% [95% CI −5·8 to 11·5] vs oral treatment), and 109 (95%) of 115 patients in the 8-week group (difference 3·7% [−4·8 to 12·2] vs oral treatment). At week 96, viral suppression was maintained in 47 (84%) of 56 patients receiving oral treatment, 100 (87%) of 115 patients in the 4-week group, and 108 (94%) of 115 patients in the 8-week group. Three patients (1%) experienced protocol-defined virological failure (two in the 8-week group; one in the oral treatment group). Injection-site reactions were mild (3648 [84%] of 4360 injections) or moderate (673 [15%] of 4360 injections) in intensity and rarely resulted in discontinuation (two [<1%] of 230 patients); injection-site pain was reported most frequently. Serious adverse events during maintenance were reported in 22 (10%) of 230 patients in the intramuscular groups (4-week and 8-week groups) and seven (13%) of 56 patients in the oral treatment group; none were drug related. Interpretation The two-drug combination of all-injectable, long-acting cabotegravir plus rilpivirine every 4 weeks or every 8 weeks was as effective as daily three-drug oral therapy at maintaining HIV-1 viral suppression through 96 weeks and was well accepted and tolerated. Funding ViiV Healthcare and Janssen R&D

Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch

Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

Réponses de PME à l'initiative d'une organisation territoriale pour la promotion de la RSE. Une opération animée par le Parc Naturel Régional du Livradois-Forez (Auvergne, France)

International audienceCe papier a pour objet de présenter l'analyse des perceptions et comportements des chefs d'entreprise de PME industrielles à l'égard non seulement de la RSE, mais aussi à l'égard de cette démarche spécifique initiée et animée par un acteur territorial, le PNR du Livradois-Forez, en faveur de la diffusion de cette RSE. Cette démarche de promotion de la RSE est baptisée DERSELF pour « développement de la responsabilité sociétale des entreprises du Livradois-Forez ». Sa conception par le PNR , acteur territorial, s'appuyait sur deux hypothèses : 1- la RSE est bonne pour le développement du territoire et 2- pour promouvoir et renforcer la RSE il y a un intérêt à renforcer les relations inter-entreprises dans une approche territoriale. L'étude repose sur une enquête auprès de 16 chefs d'entreprises