Trials

BACKGROUND: An international workshop on population health intervention research (PHIR) was organized to foster exchanges between experts from different disciplines and different fields. AIMS: This paper aims to summarize the discussions around one of the issues addressed: the place or role of pilot studies in PHIR. Pilot studies are well-established in biomedical research, but the situation is more ambiguous for PHIR, in which a pilot study could refer to different purposes. METHODS: The workshop included formal presentations of participants and moderated discussions. An oral synthesis was carried out by a rapporteur to validate by expert consensus the key points of the discussion and the recommendations. All discussions have been recorded and fully transcribed. DISCUSSION: PHIR generally addresses complex interventions. Thus, numerous tasks may be required to inform the intervention and test different aspects of its design and implementation. While in clinical research the pilot study mainly concerns the preparation of the trial, in PHIR the pilot study focuses on the preparation of both the intervention and the trial. In particular, pilot studies in PHIR could be used for viability evaluation and theory development. RECOMMENDATIONS FROM THE WORKSHOP PARTICIPANTS: The following recommendations were generated by consensus from the workshop discussions: i) terms need to be clarified for PHIR; ii) reporting and publication should be standardized and transparency should be promoted; iii) the objectives and research questions should drive the methods used and be clearly stated; iv) a pilot study is generally needed for complex intervention evaluation and for research-designed programs; and v) for field-designed programs, it is important to integrate evaluability assessments as pilot studies . CONCLUSION: Pilot studies play an important role in intervention development and evaluation. In particular, they contribute to a better understanding of the mechanisms of intervention and the conditions of its applicability and transferability. Pilot studies could therefore facilitate evidence-based decisions about design and conduct of main studies aimed to generate evidence to inform public health policy

Population health intervention research: what is the place for pilot studies?

BACKGROUND: An international workshop on population health intervention research (PHIR) was organized to foster exchanges between experts from different disciplines and different fields. AIMS: This paper aims to summarize the discussions around one of the issues addressed: the place or role of pilot studies in PHIR. Pilot studies are well-established in biomedical research, but the situation is more ambiguous for PHIR, in which a pilot study could refer to different purposes. METHODS: The workshop included formal presentations of participants and moderated discussions. An oral synthesis was carried out by a rapporteur to validate by expert consensus the key points of the discussion and the recommendations. All discussions have been recorded and fully transcribed. DISCUSSION: PHIR generally addresses complex interventions. Thus, numerous tasks may be required to inform the intervention and test different aspects of its design and implementation. While in clinical research the pilot study mainly concerns the preparation of the trial, in PHIR the pilot study focuses on the preparation of both the intervention and the trial. In particular, pilot studies in PHIR could be used for viability evaluation and theory development. RECOMMENDATION FROM THE WORKSHOP PARTICIPANTS: The following recommendations were generated by consensus from the workshop discussions: i) terms need to be clarified for PHIR; ii) reporting and publication should be standardized and transparency should be promoted; iii) the objectives and research questions should drive the methods used and be clearly stated; iv) a pilot study is generally needed for complex intervention evaluation and for research-designed programs; and v) for field-designed programs, it is important to integrate evaluability assessments as pilot studies. CONCLUSION: Pilot studies play an important role in intervention development and evaluation. In particular, they contribute to a better understanding of the mechanisms of intervention and the conditions of its applicability and transferability. Pilot studies could therefore facilitate evidence-based decisions about design and conduct of main studies aimed to generate evidence to inform public health policy

TABADO: "Evaluation of a smoking cessation program among Adolescents in Vocational Training Centers": Study protocol

<p>Abstract</p> <p>Background</p> <p>Most of the efforts to reduce teenagers' tobacco addiction have focused on smoking prevention and little on smoking cessation. A smoking cessation program (TABADO study), associating pharmacologic and cognitive-behavioural strategy, on a particularly vulnerable population (vocational trainees), was developed. This study aims to evaluate the efficacy of the program which was offered to all smokers in a population aged 15 to 20 years in Vocational Training Centers (VTC). This paper presents the TABADO study protocol.</p> <p>Methods</p> <p>The study is quasi-experimental, prospective, evaluative and comparative and takes place during the 2 years of vocational training. The final population will be composed of 2000 trainees entering a VTC in Lorraine, France, during the 2008-2009 period. The intervention group (1000 trainees) benefited from the TABADO program while no specific intervention took place in the "control" group (1000 trainees) other than the treatment and education services usually available. Our primary outcome will be the tobacco abstinence rate at 12 months.</p> <p>Discussion</p> <p>If the program proves effective, it will be a new tool in the action against smoking in populations that have been seldom targeted until now. In addition, the approach could be expanded to other young subjects from socially disadvantaged backgrounds in the context of a public health policy against smoking among adolescents.</p> <p>Trial registration</p> <p>Clinical trial identification number is NTC00973570.</p

BMC Public Health

BACKGROUND: Population health intervention research raises major conceptual and methodological issues. These require us to clarify what an intervention is and how best to address it. This paper aims to clarify the concepts of intervention and context and to propose a way to consider their interactions in evaluation studies, especially by addressing the mechanisms and using the theory-driven evaluation methodology. MAIN TEXT: This article synthesizes the notions of intervention and context. It suggests that we consider an "interventional system", defined as a set of interrelated human and non-human contextual agents within spatial and temporal boundaries generating mechanistic configurations - mechanisms - which are prerequisites for change in health. The evaluation focal point is no longer the interventional ingredients taken separately from the context, but rather mechanisms that punctuate the process of change. It encourages a move towards theorization in evaluation designs, in order to analyze the interventional system more effectively. More particularly, it promotes theory-driven evaluation, either alone or combined with experimental designs. CONCLUSION: Considering the intervention system, hybridizing paradigms in a process of theorization within evaluation designs, including different scientific disciplines, practitioners and intervention beneficiaries, may allow researchers a better understanding of what is being investigated and enable them to design the most appropriate methods and modalities for characterizing the interventional system. Evaluation methodologies should therefore be repositioned in relation to one another with regard to a new definition of "evidence", repositioning practitioners' expertise, qualitative paradigms and experimental questions in order to address the intervention system more profoundly

SIMS: A Hybrid Method for Rapid Conformational Analysis

Proteins are at the root of many biological functions, often performing complex tasks as the result of large changes in their structure. Describing the exact details of these conformational changes, however, remains a central challenge for computational biology due the enormous computational requirements of the problem. This has engendered the development of a rich variety of useful methods designed to answer specific questions at different levels of spatial, temporal, and energetic resolution. These methods fall largely into two classes: physically accurate, but computationally demanding methods and fast, approximate methods. We introduce here a new hybrid modeling tool, the Structured Intuitive Move Selector (SIMS), designed to bridge the divide between these two classes, while allowing the benefits of both to be seamlessly integrated into a single framework. This is achieved by applying a modern motion planning algorithm, borrowed from the field of robotics, in tandem with a well-established protein modeling library. SIMS can combine precise energy calculations with approximate or specialized conformational sampling routines to produce rapid, yet accurate, analysis of the large-scale conformational variability of protein systems. Several key advancements are shown, including the abstract use of generically defined moves (conformational sampling methods) and an expansive probabilistic conformational exploration. We present three example problems that SIMS is applied to and demonstrate a rapid solution for each. These include the automatic determination of ﾑﾑactiveﾒﾒ residues for the hinge-based system Cyanovirin-N, exploring conformational changes involving long-range coordinated motion between non-sequential residues in Ribose- Binding Protein, and the rapid discovery of a transient conformational state of Maltose-Binding Protein, previously only determined by Molecular Dynamics. For all cases we provide energetic validations using well-established energy fields, demonstrating this framework as a fast and accurate tool for the analysis of a wide range of protein flexibility problems

Associations between school-based peer networks and smoking according to socioeconomic status and tobacco control context:protocol for a mixed method systematic review

Background Smoking remains a major public health concern. School-based social networks influence uptake of smoking among peers. During the past two decades, the UK macro-systemic context within which schools are nested and interact with has changed, with anti-smoking norms having become set at a more macro-systemic level. Whilst the overall prevalence of smoking in the UK has decreased, inequality has prevailed. It is plausible that the influence of school-based social networks on smoking uptake may vary according to socioeconomic status. Therefore, this study aims to understand how social influence on smoking among adolescents has changed in line with variance within and between contexts according to time and geography. Methods The following databases will be searched: Medline, PsycINFO, Embase, Applied Social Sciences Index and Abstracts (ASSIA), British Education Index, Sociological abstracts, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Education Resources Information Center (ERIC) and Scopus. Additional searches will include reference checking of key papers, citation tracking, word of mouth and grey literature searches. The search strategies will incorporate terms relating to smoking, adolescents, schools, peers, network analysis and qualitative research. Titles and abstracts and full texts will be independently screened and assessed for quality by at least two researchers. Included studies will be assessed for quality, and data will be extracted for synthesis, including participant characteristics, setting and tobacco control context, study design and methods, analysis and results and conclusions. Quantitative findings will be narratively synthesised, whilst a lines of argument synthesis combined with refutational analysis will be employed to synthesise qualitative data. Both sets of findings will be charted on a timeline to add context to network findings and obtain an enhanced understanding of changes over time. Discussion This protocol is for a mixed methods synthesis of both social network findings, to investigate social structures and qualitative studies, to elicit contextual information. The review will synthesise changes in the context of social influence on adolescent smoking over time and geographically. As context is increasingly recognised as a key source of complexity, this enhanced understanding will help to inform future interventions targeting smoking through social influence. This will help to enhance their relevance to context, subsequent effectiveness and targeting of inequalities

Modeling and design by hierarchical natural moves

We develop a unique algorithm implemented in the program MOSAICS (Methodologies for Optimization and Sampling in Computational Studies) that is capable of nanoscale modeling without compromising the resolution of interest. This is achieved by modeling with customizable hierarchical degrees of freedom, thereby circumventing major limitations of conventional molecular modeling. With the emergence of RNA-based nanotechnology, large RNAs in all-atom representation are used here to benchmark our algorithm. Our method locates all favorable structural states of a model RNA of significant complexity while improving sampling accuracy and increasing speed many fold over existing all-atom RNA modeling methods. We also modeled the effects of sequence mutations on the structural building blocks of tRNA-based nanotechnology. With its flexibility in choosing arbitrary degrees of freedom as well as in allowing different all-atom energy functions, MOSAICS is an ideal tool to model and design biomolecules of the nanoscale