KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype.

To characterise the genetics of splenic marginal zone lymphoma (SMZL), we performed whole exome sequencing of 16 cases and identified novel recurrent inactivating mutations in Kruppel-like factor 2 (KLF2), a gene whose deficiency was previously shown to cause splenic marginal zone hyperplasia in mice. KLF2 mutation was found in 40 (42%) of 96 SMZLs, but rarely in other B-cell lymphomas. The majority of KLF2 mutations were frameshift indels or nonsense changes, with missense mutations clustered in the C-terminal zinc finger domains. Functional assays showed that these mutations inactivated the ability of KLF2 to suppress NF-κB activation by TLR, BCR, BAFFR and TNFR signalling. Further extensive investigations revealed common and distinct genetic changes between SMZL with and without KLF2 mutation. IGHV1-2 rearrangement and 7q deletion were primarily seen in SMZL with KLF2 mutation, while MYD88 and TP53 mutations were nearly exclusively found in those without KLF2 mutation. NOTCH2, TRAF3, TNFAIP3 and CARD11 mutations were observed in SMZL both with and without KLF2 mutation. Taken together, KLF2 mutation is the most common genetic change in SMZL and identifies a subset with a distinct genotype characterised by multi-genetic changes. These different genetic changes may deregulate various signalling pathways and generate cooperative oncogenic properties, thereby contributing to lymphomagenesis.

Reliability of P-drive in occupational therapy following a short training session: A promising instrument measuring seniors' on-road driving competencies

Introduction Occupational therapists could play an important role in facilitating driving cessation for ageing drivers. This, however, requires an easy-to-learn, standardised on-road evaluation method. This study therefore investigates whether use of P-drive' could be reliably taught to occupational therapists via a short half-day training session. Method Using the English 26-item version of P-drive, two occupational therapists evaluated the driving ability of 24 home-dwelling drivers aged 70 years or over on a standardised on-road route. Experienced driving instructors' on-road, subjective evaluations were then compared with P-drive scores. Results Following a short half-day training session, P-drive was shown to have almost perfect between-rater reliability (ICC2,1=0.950, 95% CI 0.889 to 0.978). Reliability was stable across sessions including the training phase even if occupational therapists seemed to become slightly less severe in their ratings with experience. P-drive's score was related to the driving instructors' subjective evaluations of driving skills in a non-linear manner (R-2=0.445, p=0.021). Conclusion P-drive is a reliable instrument that can easily be taught to occupational therapists and implemented as a way of standardising the on-road driving test.

Involuntary outpatient treatment for mental health problems in Switzerland: a literature review.

BACKGROUND: In 2008, the Swiss Civil Code was amended. From 1 January 2013, each Swiss canton may propose specific provisions for involuntary outpatient treatment (community treatment orders (CTOs)) for individuals with mental disorders. AIM: This review catalogues the legal provisions of the various Swiss cantons for CTOs and outlines the differences between them. It sets this in the context of variations in clinical provisions between the cantons. METHODS: Databases were searched to obtain relevant publications about CTOs in Switzerland. The Swiss Medical Association, Swiss Federal Statistical Office, Swiss Health Observatory and all the 26 Cantonal medical officers were contacted to complete the information. Conférence des cantons en matière de protection des mineurs et des adultes (COPMA), the authority which monitors guardianship legislation, and Pro Mente Sana, a patients' right association, were also approached. RESULTS: Three articles about CTOs in Switzerland were identified. Psychiatric provisions vary considerably between cantons and only a few could provide complete or even partial figures for rates of compulsion in previous years. Prior to 2013, only 6 of the 20 cantons, for which information was returned, had any provision for CTOs. Now, every canton has some form of legal basis but the level of detail is often limited. In eight cantons, the powers of the measure are not specified (for example, use of medication). In 12 cantons, the maximum duration of the CTO is not specified. German speaking cantons and rural cantons are more likely to specify the details of CTOs. CONCLUSION: Highly variable Swiss provision for CTOs is being introduced despite the absence of convincing international evidence for their effectiveness or good quality data on current coercive practice. Careful monitoring and assessment of these new cantonal provisions are essential.

A phase IIa randomised clinical study of GNbAC1, a humanised monoclonal antibody against the envelope protein of multiple sclerosis-associated endogenous retrovirus in multiple sclerosis patients.

BACKGROUND: GNbAC1 is an immunoglobulin (IgG4) humanised monoclonal antibody against multiple sclerosis-associated retrovirus (MSRV)-Env, a protein of endogenous retroviral origin, expressed in multiple sclerosis (MS) lesions, which is pro-inflammatory and inhibits oligodendrocyte precursor cell differentiation. OBJECTIVE: This is a randomised, double-blind placebo-controlled dose-escalation study followed by a six-month open-label phase to test GNbAC1 in MS patients. The primary objective was to assess GNbAC1 safety in MS patients, and the other objectives were pharmacokinetic and pharmacodynamic assessments. METHODS: Ten MS patients were randomised into two cohorts to receive a single intravenous infusion of GNbAC1/placebo at doses of 2 or 6 mg/kg. Then all patients received five infusions of GNbAC1 at 2 or 6 mg/kg at four-week intervals in an open-label setting. Safety, brain magnetic resonance imaging (MRI), pharmacokinetics, immunogenicity, cytokines and MSRV RNA expression were studied. RESULTS: All patients completed the study. GNbAC1 was well tolerated in all patients. GNbAC1 pharmacokinetics is dose-linear with mean elimination half-life of 27-37 d. Anti-GNbAC1 antibodies were not detected. Cytokine analysis did not indicate an adverse effect. MSRV-transcripts showed a decline after the start of treatment. Nine patients had stable brain lesions at MRI. CONCLUSION: The safety, pharmacokinetic profile, and pharmacodynamic responses to GNbAC1 are favourable in MS patients over a six-month treatment period.

A promising new device for the prevention of parastomal hernia.

Parastomal hernia (PSH) is the most frequent long-term stoma complication with serious negative effects on quality of life. Surgical revision is often required and has a substantial morbidity and recurrence rate. The development of PSH requires revisional surgery with a substantial perioperative morbidity and high failure rate in the long-term follow-up. Prophylactic parastomal mesh insertion during stoma creation has the potential to reduce the rate of PSH, but carries the risk of early and late mesh-related complications such as infection, fibrosis, mesh shrinkage, and/or bowel erosion. We developed a new stomaplasty ring (KORING), which is easy to implant, avoids potential mesh-related complications, and has a high potential of long-term prevention of PSH. Here we describe the technique and the first use.

Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial.

BACKGROUND: The recent large randomized controlled trial of glutamine and antioxidant supplementation suggested that high-dose glutamine is associated with increased mortality in critically ill patients with multiorgan failure. The objectives of the present analyses were to reevaluate the effect of supplementation after controlling for baseline covariates and to identify potentially important subgroup effects. MATERIALS AND METHODS: This study was a post hoc analysis of a prospective factorial 2 × 2 randomized trial conducted in 40 intensive care units in North America and Europe. In total, 1223 mechanically ventilated adult patients with multiorgan failure were randomized to receive glutamine, antioxidants, both glutamine and antioxidants, or placebo administered separate from artificial nutrition. We compared each of the 3 active treatment arms (glutamine alone, antioxidants alone, and glutamine + antioxidants) with placebo on 28-day mortality. Post hoc, treatment effects were examined within subgroups defined by baseline patient characteristics. Logistic regression was used to estimate treatment effects within subgroups after adjustment for baseline covariates and to identify treatment-by-subgroup interactions (effect modification). RESULTS: The 28-day mortality rates in the placebo, glutamine, antioxidant, and combination arms were 25%, 32%, 29%, and 33%, respectively. After adjusting for prespecified baseline covariates, the adjusted odds ratio of 28-day mortality vs placebo was 1.5 (95% confidence interval, 1.0-2.1, P = .05), 1.2 (0.8-1.8, P = .40), and 1.4 (0.9-2.0, P = .09) for glutamine, antioxidant, and glutamine plus antioxidant arms, respectively. In the post hoc subgroup analysis, both glutamine and antioxidants appeared most harmful in patients with baseline renal dysfunction. No subgroups suggested reduced mortality with supplements. CONCLUSIONS: After adjustment for baseline covariates, early provision of high-dose glutamine administered separately from artificial nutrition was not beneficial and may be associated with increased mortality in critically ill patients with multiorgan failure. For both glutamine and antioxidants, the greatest potential for harm was observed in patients with multiorgan failure that included renal dysfunction upon study enrollment.

Attitudes Toward Organizational Change among Public Middle Managers

Positive attitudes toward change (PATC) are an important current issue in public organizations facing profound financial and managerial reforms. This study aims to identify social and organizational antecedents of PATC. The investigated population is composed of middle managers working in Swiss public hospitals (N = 720), which are currently being confronted by major reforms. Partial mediation effects of organizational commitment (OC) in the relationships between independent variables and PATC are also controlled. The findings show that perceived social support (work relationships with colleagues and supervisors) as well as perceived organizational support (employee voice and participation, information and communication, work-life balance) are positively and significantly related to PATC. Stress perception is shown to have a negative impact on PATC. This article provides valuable contributions with respect to antecedents of attitudes toward change in a population of public middle managers.

'Steal me if you can!' The impact of campaign messages on associative issue ownership

Whereas extant work on issue ownership treats voters' issue ownership perceptions as independent variables to explain electoral choice or party behaviour, this article examines whether parties can, by communicating on an issue, turn voters' perceptions of issue ownership to their advantage. In contrast to most previous studies that have focused on competence ownership - measured as a party's capacity to handle an issue - this article analyses the short-term and long-term impact of campaign messages on voters' perceptions of associative ownership, which refers to the voters' spontaneous party-issue association, regardless of whether or not voters consider the party as the most competent at dealing with the issue at hand. Based on an online experimental design in Belgium, we show that parties are unable to steal issues that are associated with another party. However, by communicating on their own issues, parties can reinforce their reputation as an associative owner - but only in the short run and only if their previous ownership reputation is not overly strong.

S'inscrire dans l'espace public en tant que musulman en Suisse

En Suisse, comme dans de nombreux pays européens, l'exigence d'une représentation musulmane impose une forme d'inscription dans l'espace public d'acteurs emblématiques de l'islam. Cette contribution entend éclairer les différentes contraintes institutionnelles qui poussent les musulmans à s'inscrire différemment dans l'espace public. On distingue d'une part, une tendance s'efforçant d'apparaître dans l'espace public comme une structure confessionnelle garant de la communitas islamica. Elle est composée de communautés de la diaspora qui ont obtenu des accords auprès de la Confédération et de communautés qui se fédèrent au niveau cantonal pour constituer une représentation auprès des autorités de régulation religieuse. D'autre part, des acteurs parviennent à imposer leurs exigences d'un homo islamicus idéalisé en s'inscrivant pleinement dans l'espace médiatique au risque de prétériter la « représentation » chèrement acquise par des acteurs institutionnels

Assessing the sociology of sport: On sport organizations and critical knowledge

The purpose of this contribution is to analyse the trajectory, the challenges and the future of the sociology of sport on three levels: the internal dynamic within the specific sub-field of the sociology of sport, its interactions with sociology and sport sciences, and its relation with sport organizations. The paper notes that the changes of the trajectory of the sociology of sport, first leaning on the profession of physical education teacher and then to sport sciences, as important consequences. Because most of the sociologists specialized in sport are working in sport sciences departments, the most important consequence is the dependency on sport sciences rather than on sociology. Compared to other fields of sociology, it means challenging other sciences for recognition. The paper argues that to face the threat of a marginalization within the field of sport science, the future of sociology of sport could be to fight for an external recognition. Applying sociology could spread critical views that are necessary to sport organizations. It could also give sociologists access to very interesting data, which can help producing good research, and give it a greater legitimacy within sport sciences. However, it is a risky strategy because of the necessity for the sociologists to stay critical both on sporting organization and on their own work.

Participation rates for organized colorectal cancer screening programmes: an international comparison.

OBJECTIVE: Participation, an indicator of screening programme acceptance and effectiveness, varies widely in clinical trials and population-based colorectal cancer (CRC) screening programmes. We aimed to assess whether CRC screening participation rates can be compared across organized guaiac fecal occult blood test (G-FOBT)/fecal immunochemical test (FIT)-based programmes, and what factors influence these rates. METHODS: Programme representatives from countries participating in the International Cancer Screening Network were surveyed to describe their G-FOBT/FIT-based CRC screening programmes, how screening participation is defined and measured, and to provide participation data for their most recent completed screening round. RESULTS: Information was obtained from 15 programmes in 12 countries. Programmes varied in size, reach, maturity, target age groups, exclusions, type of test kit, method of providing test kits and use, and frequency of reminders. Coverage by invitation ranged from 30-100%, coverage by the screening programme from 7-67.7%, overall uptake/participation rate from 7-67.7%, and first invitation participation from 7-64.3%. Participation rates generally increased with age and were higher among women than men and for subsequent compared with first invitation participation. CONCLUSION: Comparisons among CRC screening programmes should be made cautiously, given differences in organization, target populations, and interpretation of indicators. More meaningful comparisons are possible if rates are calculated across a uniform age range, by gender, and separately for people invited for the first time vs. previously.

Developing a theoretical framework using a nursing perspective to investigate perceived health in the "Sandwich Generation" group

Coexisting workloads from professional, household and family, and caregiving activities for frail parents expose middle-aged individuals, the so-called "Sandwich Generation", to potential health risks. Current trends suggest that this situation will continue or increase. Thus SG health promotion has become a nursing concern. Most existing research considers coexisting workloads a priori pathogenic. Most studies have examined the association of one, versus two, of these three activities with health. Few studies have used a nursing perspective. This article presents the development of a framework based on a nursing model. We integrated Siegrist's Effort-Reward Imbalance middle-range theory into "Neuman Systems Model". The latter was chosen for its salutogenic orientation, its attention to preventive nursing interventions and the opportunity it provides to simultaneously consider positive and negative perceptions of SG health and SG coexisting workloads. Finally, it facilitated a theoretical identification of health protective factors.

Police work and new 'security devices' : a tale from the beat

Mobile technologies have brought about major changes in police equipment and police work. If a utopian narrative remains strongly linked to the adoption of new technologies, often formulated as 'magic bullets' to real occupational problems, there are important tensions between their 'imagined' outcomes and the (unexpected) effects that accompany their daily 'practical' use by police officers. This article offers an analysis of police officers' perceptions and interactions with security devices. In so doing, it develops a conceptual typology of strategies for coping with new technology inspired by Le Bourhis and Lascoumes: challenging, neutralizing and diverting. To that purpose, we adopt an ethnographic approach that focuses on the discourses, practices and actions of police officers in relation to three security devices: the mobile digital terminal, the mobile phone and the body camera. Based on a case study of a North American municipal police department, the article addresses how these technological devices are perceived and experienced by police officers on the beat.

The comparability of quantitative surveys on sport participation in France (1967-2010)

Results from quantitative surveys enable historians, sociologists and demographers to describe and analyse the evolution of sport participation in France from 1967 to 2010. However, most of these social scientists use the results of these surveys to create very different methodologies without having studied the surveys' empirical data or databases. In this article, we demonstrate how we have attempted to establish a basis for comparability of the surveys by analysing these databases. As a result of our work, certain affirmations on which the history of sport participation in France has long been based may be called into question or even changed.