Selenocysteine Insertion Sequence Binding Protein 2L Is Implicated as a Novel Post-Transcriptional Regulator of Selenoprotein Expression

The amino acid selenocysteine (Sec) is encoded by UGA codons. Recoding of UGA from stop to Sec requires a Sec insertion sequence (SECIS) element in the 3′ UTR of selenoprotein mRNAs. SECIS binding protein 2 (SBP2) binds the SECIS element and is essential for Sec incorporation into the nascent peptide. SBP2-like (SBP2L) is a paralogue of SBP2 in vertebrates and is the only SECIS binding protein in some invertebrates where it likely directs Sec incorporation. However, vertebrate SBP2L does not promote Sec incorporation in in vitro assays. Here we present a comparative analysis of SBP2 and SBP2L SECIS binding properties and demonstrate that its inability to promote Sec incorporation is not due to lower SECIS affinity but likely due to lack of a SECIS dependent domain association that is found in SBP2. Interestingly, however, we find that an invertebrate version of SBP2L is fully competent for Sec incorporation in vitro. Additionally, we present the first evidence that SBP2L interacts with selenoprotein mRNAs in mammalian cells, thereby implying a role in selenoprotein expression

A Survey on Continuous Time Computations

We provide an overview of theories of continuous time computation. These theories allow us to understand both the hardness of questions related to continuous time dynamical systems and the computational power of continuous time analog models. We survey the existing models, summarizing results, and point to relevant references in the literature

Acute cholecystitis – early laparoskopic surgery versus antibiotic therapy and delayed elective cholecystectomy: ACDC-study

<p>Abstract</p> <p>Background</p> <p>Acute cholecystitis occurs frequently in the elderly and in patients with gall stones. Most cases of severe or recurrent cholecystitis eventually require surgery, usually laparoscopic cholecystectomy in the Western World. It is unclear whether an initial, conservative approach with antibiotic and symptomatic therapy followed by delayed elective surgery would result in better morbidity and outcome than immediate surgery. At present, treatment is generally determined by whether the patient first sees a surgeon or a gastroenterologist. We wish to investigate whether both approaches are equivalent. The primary endpoint is the morbidity until day 75 after inclusion into the study.</p> <p>Design</p> <p>A multicenter, prospective, randomized non-blinded study to compare treatment outcome, complications and 75-day morbidity in patients with acute cholecystitis randomized to laparoscopic cholecystectomy within 24 hours of symptom onset or antibiotic treatment with moxifloxacin and subsequent elective cholecystectomy. For consistency in both arms moxifloxacin, a fluorquinolone with broad spectrum of activity and high bile concentration is used as antibiotic. Duration: October 2006 – November 2008</p> <p>Organisation/Responsibility</p> <p>The trial was planned and is being conducted and analysed by the Departments of Gastroenterology and General Surgery at the University Hospital of Heidelberg according to the ethical, regulatory and scientific principles governing clinical research as set out in the Declaration of Helsinki (1989) and the Good Clinical Practice guideline (GCP).</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00447304</p

Recruiting to a large-scale physical activity randomised controlled trial – experiences with the gift of hindsight

Background: Recruitment issues continue to impact a large number of trials. Sharing recruitment information is vital to support researchers to accurately predict recruitment and to manage the risk of poor recruitment during study design and implementation. The purpose of this paper is to build on the knowledge available to researchers on recruiting to community based trials. Methods: A critical commentary of the recruitment challenges encountered during the ‘Booster’ Study, a randomised controlled trial which investigated the effectiveness of a Motivational Interviewing style intervention on the maintenance of physical activity. An overview of recruitment is provided, as well as strategies employed to recruit prospective participants and possible barriers to recruitment. Results: Two hundred and eighty two people, 47% of the original target, were recruited through mail-outs with secondary recruitment pathways yielding no additional participants. The research team encountered problems re-contacting interested participants and providing study materials in non-English languages. A lower response rate to the mail-out and a greater number of non-contactable participants in the full study compared to the pilot study resulted in a smaller pool of eligible participants from the brief intervention eligible for recruitment into the RCT. Conclusion: Despite utilising widely accepted recruitment strategies and incorporating new recruitment tactics in response to challenges, the ‘Booster’ study failed to randomise a sufficient number of participants. Recruitment to community based, behavioural interventions may face different challenges than trials based in clinical or primary care pathways. Specific challenges posed by the complexity of the study design and problems with staffing and resources were exacerbated by the need to revise upwards the number of mailed invitations as a result of the pilot study. Researchers should ensure study design is facilitative to recruitment and consider the implications of changing recruitment on the operational aspects of the trial. Where possible the impact of new strategies should be measured, and recruitment successes and challenges shared with those planning similar studies. The study was a registered controlled trial (ISRCTN56495859 12 Feb 2009; NCT00836459 03 Feb 2009) KEYWORDS: Recruitment, Physical Activity, mail-outs, BOOSTER, behaviour maintenance

Colorectal cancer health services research study protocol: the CCR-CARESS observational prospective cohort project

BACKGROUND: Colorectal cancers are one of the most common forms of malignancy worldwide. But two significant areas of research less studied deserve attention: health services use and development of patient stratification risk tools for these patients. METHODS:DESIGN: a prospective multicenter cohort study with a follow up period of up to 5 years after surgical intervention. Participant centers: 22 hospitals representing six autonomous communities of Spain. Participants/Study population: Patients diagnosed with colorectal cancer that have undergone surgical intervention and have consented to participate in the study between June 2010 and December 2012. Variables collected include pre-intervention background, sociodemographic parameters, hospital admission records, biological and clinical parameters, treatment information, and outcomes up to 5 years after surgical intervention. Patients completed the following questionnaires prior to surgery and in the follow up period: EuroQol-5D, EORTC QLQ-C30 (The European Organization for Research and Treatment of Cancer quality of life questionnaire) and QLQ-CR29 (module for colorectal cancer), the Duke Functional Social Support Questionnaire, the Hospital Anxiety and Depression Scale, and the Barthel Index. The main endpoints of the study are mortality, tumor recurrence, major complications, readmissions, and changes in health-related quality of life at 30 days and at 1, 2, 3 and 5 years after surgical intervention. STATISTICAL ANALYSIS: In relation to the different endpoints, predictive models will be used by means of multivariate logistic models, Cox or linear mixed-effects regression models. Simulation models for the prediction of discrete events in the long term will also be used, and an economic evaluation of different treatment strategies will be performed through the use of generalized linear models. DISCUSSION: The identification of potential risk factors for adverse events may help clinicians in the clinical decision making process. Also, the follow up by 5 years of this large cohort of patients may provide useful information to answer different health services research questions

A structured review of reasons for ecstasy use and related behaviours: pointers for future research

Abstract Background While the health risks of using ecstasy warrant intervention development, a recent meta-analysis of determinants of ecstasy use identified a number of lacunae in the literature. Specifically, no studies were included that address behaviours other than 'using ecstasy' (e.g. 'trying out ecstasy' or 'ceasing ecstasy use'). However, because meta-analyses aim to integrate study results quantitatively, the resulting rigid exclusion criteria cause many studies to be discarded on the basis of their qualitative methodology. Such qualitative studies may nonetheless provide valuable insights to guide future research. To provide an overview of these insights regarding ecstasy use, the current study summarizes and combines what is known from qualitative and exploratory quantitative literature on ecstasy use. Methods The databases PsycINFO and MedLine were searched for publications reporting reasons for ecstasy use and related behaviour, and the results were structured and discussed per behaviour and compared over behaviours. Results Two main categories of reasons were found. The first category comprised reasons to start using ecstasy, use ecstasy, use ecstasy more often, and refrain from ceasing ecstasy use. The second category comprised reasons to refrain from starting to use ecstasy, use less ecstasy, and cease using ecstasy. Reasons for related behaviours within each of these two categories appear to differ, but not as substantially as between the two categories. A large number of reasons that were not yet explored in quantitative research emerged. Conclusion The current summary and combination of exploratory studies yields useful lists of reasons for each behaviour. Before these lists can inform interventions, however, they beg quantitative verification. Also, similarity of determinant configurations of different behaviours can be assessed by addressing determinants of several behaviours in one study. Another important finding is that meta-analytical integration of the literature may overlook important findings and implications. Thus, qualitative reviews remain useful instruments in setting the research agenda.</p

Changes in sedentary behaviour in European Union adults between 2002 and 2017

Abstract: Background: Sedentary behaviour (SB) has been identified as an important mortality risk factor. Health organizations have recognised SB as a public health challenge with major health, social, and economic consequences. Researchers have alerted the need to develop specific strategies, to monitor, prevent, and reduce SB. However, there is no systematic analysis of the SB changes in European Union adults. We aimed to examine SB changes between 2002 and 2017 in the European Union (EU) adult population. Methods: SB prevalence (>4h30mins of sitting time/day) of 96,004 adults as a whole sample and country-by-country was analysed in 2002, 2005, 2013, and 2017 of the Sport and Physical Activity EU Special Eurobarometers’ data. The SB question of a modified version of the International Physical Activity Questionnaire was considered. SB prevalence between countries and within years was analysed with a χ2 test, and SB between genders was analysed with the Z-Score test for two population proportions. Results: An association between the SB prevalence and the years was found (p < 0.001), with increases for the whole sample (2002: 49.3%, 48.5–50.0 95% confidence interval (CI); 2017: 54.5%, 53.9–55.0 95% CI) and men (2002: 51.2%, 50.0–52.4 95% CI; 2017: 55.8%, 55.0–56.7 95% CI) and women (2002: 47.6%, 46.6–48.7 95% CI; 2017: 53.4%, 52.6–54.1 95% CI) separately. The adjusted standardised residuals showed an increase in the observed prevalence versus the expected during 2013 and 2017 for the whole sample and women and during 2017 for men. For all years, differences were observed in the SB prevalence between countries for the whole sample, and men and women separately (p < 0.001). Besides, the SB prevalence was always higher in men versus women in the overall EU sample (p < 0.001). Conclusions: SB prevalence increased between 2002 and 2017 for the EU as a whole and for both sexes separately. Additionally, differences in SB prevalence were observed for all years between EU countries in the whole sample and both sexes separately. Lastly, SB was consistently higher in men than women. These findings reveal a limited impact of current policies and interventions to tackle SB at the EU population level