Social contexts of sports-practicing youths' hazardous drinking.

Sports-practicing youths are at an elevated risk for alcohol use and misuse. Although much attention has recently been given to depicting subgroups facing the greatest threats, little evidence exists on the contexts in which their drinking takes place. Using data from a cross-sectional study on youth sports participation and substance use in the French-speaking part of Switzerland, this study focused on the social contexts associated with hazardous drinking of 894 sports-practicing adolescents aged 16 to 20. Divided between those who had been drunk in the last month (hazardous drinkers, n = 315) and those who had not (n = 579), sports-practicing adolescents were compared on reported gatherings (sports-related, sports-unrelated, mixed) likely linked to their drinking behaviour. Mixed social contexts, followed by sports-unrelated ones, were reported as the most common context by both male and female youths who practiced sports. After controlling for several possible confounders, male hazardous drinkers were more than 3 times more likely to report sports-unrelated social contexts as the most common, compared to sport-related ones, while females were more than 7 times more likely to do so. Our findings seem to indicate that, rather than focusing only on sports-related factors, prevention of alcohol misuse among sports-practicing youths should also pay attention to the social contextualisation of their hazardous drinking.

Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications

OBJECTIVE: To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. DESIGN: Cohort of protocols of randomised controlled trial and subsequent full journal publications. SETTING: Six research ethics committees in Switzerland, Germany, and Canada. DATA SOURCES: 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. RESULTS: Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. CONCLUSIONS: Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials.

The TREAT-NMD DMD Global Database: Analysis of More than 7,000 Duchenne Muscular Dystrophy Mutations.

Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations).

An analysis of protocols and publications suggested that most discontinuations of clinical trials were not based on preplanned interim analyses or stopping rules.

OBJECTIVES: To investigate the frequency of interim analyses, stopping rules, and data safety and monitoring boards (DSMBs) in protocols of randomized controlled trials (RCTs); to examine these features across different reasons for trial discontinuation; and to identify discrepancies in reporting between protocols and publications. STUDY DESIGN AND SETTING: We used data from a cohort of RCT protocols approved between 2000 and 2003 by six research ethics committees in Switzerland, Germany, and Canada. RESULTS: Of 894 RCT protocols, 289 prespecified interim analyses (32.3%), 153 stopping rules (17.1%), and 257 DSMBs (28.7%). Overall, 249 of 894 RCTs (27.9%) were prematurely discontinued; mostly due to reasons such as poor recruitment, administrative reasons, or unexpected harm. Forty-six of 249 RCTs (18.4%) were discontinued due to early benefit or futility; of those, 37 (80.4%) were stopped outside a formal interim analysis or stopping rule. Of 515 published RCTs, there were discrepancies between protocols and publications for interim analyses (21.1%), stopping rules (14.4%), and DSMBs (19.6%). CONCLUSION: Two-thirds of RCT protocols did not consider interim analyses, stopping rules, or DSMBs. Most RCTs discontinued for early benefit or futility were stopped without a prespecified mechanism. When assessing trial manuscripts, journals should require access to the protocol.

Muistatko?: kukkia keväiseltä niityltä

Lisäpainokset: 2. p. 1920.

Enhancement of ultrafiltration process by pretreatment in recovery of hemicelluloses from wood extracts

Hemicelluloses are potential raw material for several items produced in future wood-based biorefineries. One possible method for recovering hemicelluloses from wood extracts is ultrafiltration (UF). However, low filtration capacities and severe fouling restrict the use of tight UF membranes in the treatment of wood extracts. The lack of suitable commercial membranes creates a need for pretreatment which would decrease fouling and increase the filtration capacity. This thesis focuses on the evaluation of the possibility to improve the filtration capacity and decrease fouling with the pretreatment of wood extracts. Methods which remove harmful compounds and methods which degrade them are studied, as well as combinations of the methods. The tested pretreatments have an influence on both the concentration of different compounds and the molecular mass distribution of the compounds in the extract. This study revealed that in addition to which kind of compounds were removed, also the change in molecular size distribution affected the filtration capacity significantly. It was shown that the most harmful compounds for the filtration capacity of the hydrophobic 5 kDa membrane were the ones capable of permeating the membrane and fouling also the inner membrane structure. Naturally, the size of the most harmful compounds depends on the used UF membrane and is thus case-specific. However, in the choice of the pretreatment method, the focus should be on the removal of harmful compound sizes rather than merely on the total amount of removed foulants. The results proved that filtration capacity can be increased with both adsorptive and oxidative pretreatments even by hundreds of per cents. For instance, the use of XAD7 and XAD16 adsorbents increased the average flux in the UF of a birch extract from nearly zero to 107 kg/(m2h) and 175 kg/(m2h), respectively. In the treatment of a spruce extract, oxidation by pulsed corona discharge (PCD) increased the flux in UF from 46 kg/(m2h) to 158 kg/(m2h). Moreover, when a birch extract batch was treated with laccase enzyme, the flux in UF increased from 15 kg/(m2h) to 36 kg/(m2h). However, fouling was decreased only by adsorptive pretreatment while oxidative methods had a negligible or even negative impact on it. This demonstrates that filtration capacity and fouling are affected by different compounds and mechanisms. The results of this thesis show that filtration capacity can be improved and fouling decreased through appropriate pretreatment. However, the choice of the best possible pretreatment is case-specific and depends on the wood extract and the membrane used. Finding the best option requires information on the extract content and membrane characteristics as well as on the filtration performance of the membrane in the prevailing conditions and a multivariate approach. On the basis of this study, it can be roughly concluded that adsorptive pretreatment improves the filtration capacity and decreases fouling rather reliably, but it may lead to significant hemicellulose losses. Oxidation reduces the loss of valuable hemicelluloses and could improve the filtration capacity, but fouling challenges may remain. Combining oxidation with adsorptive pretreatment was not a solution for avoiding hemicellulose losses in the tested cases.

L'Écho de Paris

1886/08/23 (Numéro 894).

Evolution du temps requis des contribuables par l'impôt fédéral canadien sur le revenu personnel entre 1966 et 1993.

Rapport de recherche