Understanding implementation success: protocol for an in-depth, mixed-methods process evaluation of a cluster randomised controlled trial testing methods to improve detection of Lynch syndrome in Australian hospitals.

INTRODUCTION:In multisite intervention trials, implementation success often varies widely across settings. Process evaluations are crucial to interpreting trial outcomes and understanding contextual factors and causal chains necessary for successful implementation. Lynch syndrome is a hereditary cancer predisposition conferring an increased risk of colorectal, endometrial and other cancer types. Despite systematic screening protocols to identify Lynch syndrome, the condition remains largely underdiagnosed. The Hide and Seek Project ('HaSP') is a cluster randomised controlled trial determining the effectiveness of two approaches to improving Lynch syndrome detection at eight Australian hospital networks. To enhance widespread implementation of optimal Lynch syndrome identification, there is a need to understand not only what works, but also why, in what contexts, and at what costs. Here we describe an in-depth investigation of factors influencing successful implementation of procedures evaluated in the HaSP trial. METHODS AND ANALYSIS:A mixed-methods, theory-driven process evaluation will be undertaken in parallel to the HaSP trial. Data will include: interviews of Implementation Leads and Lynch syndrome stakeholders, pre-post implementation questionnaires, audio analysis of meetings and focus groups, observation of multidisciplinary team meetings, fidelity checklists and project log analysis. Results will be triangulated and coded, drawing on the Theoretical Domains Framework, Consolidated Framework for Implementation Research and Proctor's implementation outcomes. ETHICS AND DISSEMINATION:Use of a theory-based process evaluation will enhance interpretation and generalisability of HaSP trial findings, and contribute to the implementation research field by furthering understanding of the conditions necessary for implementation success. Ethical approval has been granted and results will be disseminated via publications in peer-reviewed journals and conference presentations. At trial completion, key findings will be fed back to sites to enable refinement of intervention strategies, both in the context of Lynch syndrome and for the possible generalisability of intervention components in other genetic and broader clinical specialties. HASP TRIAL REGISTRATION NUMBER:Australian New Zealand Clinical Trials Registry (Identifier: ACTRN12618001072202). Registered 27 June 2018. http://www.ANZCTR.org.au/ACTRN12618001072202.aspx

A keff Search Capability in MC21

The MC21 Monte Carlo code is required to permit an individual geometric component or groups of components to be tagged as ''movable'' within some permissible range. Typical examples of such movable components would be control devices such as translating rods or rotating drums. Given this geometric information, a target multiplication factor (k{sub eff}), and a convergence criterion, MC21 will iterate on movable component positions and return a final position that reflects a k{sub eff} close to the target value. An initial version of this capability is demonstrated through modifications to MC21 that sets the geometry data structures for the movable components, calls the main Fortran-95 solver to compute k{sub eff}, and converges on the final position. This approach uses an adaptive batching algorithm that continually increases the accuracy of each successive MC21 k{sub eff} result as the movable geometry approaches the converged position

Growth in ataxia telangiectasia

BACKGROUND: Ataxia telangiectasia (A-T) is a DNA repair disorder that affects multiple body systems. Neurological problems and immunodeficiency are two important features of this disease. At this time, two main severity groups are defined in A-T: classic (the more severe form) and mild. Poor growth is a common problem in classic A-T. An objective of this study was to develop growth references for classic A-T. Another objective was to compare growth patterns in classic A-T and mild A-T with each other and with the general population, using the CDC growth references. A final objective was to examine the effects of chronic infection on height. RESULTS: We found that classic A-T patients were smaller overall, and suffered from height and weight faltering that continued throughout childhood and adolescence. When compared to the CDC growth references, the median heights and weights for both male and female patients eventually fell to or below the 3rd centile on the CDC charts. Height faltering was more pronounced in females. Birthweight was lower in the classic A-T group compared to mild A-T and the general population, whereas birth length was not. Finally, we investigated height and BMI faltering in relation to number of infections and found no association. CONCLUSIONS: Classic A-T appears to affect growth in utero. Although children appear to grow well in very early life, faltering begins early, and is unrelenting

Antonio Gramsci’s impact on critical pedagogy

This paper provides an account of Antonio Gramsci’s impact on the area of critical pedagogy. It indicates the Gramscian influence on the thinking of major exponents of the field. It foregrounds Gramsci's ideas and then indicates how they have been taken up by a selection of critical pedagogy exponents who were chosen on the strength of their identification and engagement with Gramsci's ideas, some of them even having written entire essays on Gramsci. The essay concludes with a discussion concerning an aspect of Gramsci's concerns, the question of powerful knowledge, which, in the present author's view, provides a formidable challenge to critical pedagogues.peer-reviewe

The Readability of Information and Consent Forms in Clinical Research in France

BACKGROUND: Quantitative tools have been developed to evaluate the readability of written documents and have been used in several studies to evaluate information and consent forms. These studies all showed that such documents had a low level of readability. Our objective is to evaluate the readability of Information and Consent Forms (ICFs) used in clinical research. METHODS AND FINDINGS: Clinical research protocols were collected from four public clinical research centers in France. Readability was evaluated based on three criteria: the presence of an illustration, the length of the text and its Flesch score. Potential effects of protocol characteristics on the length and readability of the ICFs were determined. Medical and statutory parts of the ICF form were analyzed separately. The readability of these documents was compared with that of everyday contracts, press articles, literary extracts and political speeches. We included 209 protocols and the corresponding 275 ICFs. The median length was 1304 words. Their Flesch readability scores were low (median: 24), and only about half that of selected press articles. ICF s for industrially sponsored and randomized protocols were the longest and had the highest readability scores. More than half (52%) of the text in ICFs concerned medical information, and this information was statistically (p<0.05) more readable (Flesch: 28) than statutory information (Flesch: 21). CONCLUSION: Regardless of the field of research, the ICFs for protocols included had poor readability scores. However, a prospective analysis of this test in French should be carried out before it is put into general use

The enigma of in vivo oxidative stress assessment: isoprostanes as an emerging target

Oxidative stress is believed to be one of the major factors behind several acute and chronic diseases, and may also be associated with ageing. Excess formation of free radicals in miscellaneous body environment may originate from endogenous response to cell injury, but also from exposure to a number of exogenous toxins. When the antioxidant defence system is overwhelmed, this leads to cell damage. However, the measurement of free radicals or their endproducts is tricky, since these compounds are reactive and short lived, and have diverse characteristics. Specific evidence for the involvement of free radicals in pathological situations has been difficult to obtain, partly owing to shortcomings in earlier described methods for the measurement of oxidative stress. Isoprostanes, which are prostaglandin-like bioactive compounds synthesized in vivo from oxidation of arachidonic acid, independently of cyclooxygenases, are involved in many human diseases, and their measurement therefore offers a way to assess oxidative stress. Elevated levels of F2-isoprostanes have also been seen in the normal human pregnancy, but their physiological role has not yet been defined. Large amounts of bioactive F2-isoprostanes are excreted in the urine in normal basal situations, with a wide interindividual variation. Their exact role in the regulation of normal physiological functions, however, needs to be explored further. Current understanding suggests that measurement of F2-isoprostanes in body fluids provides a reliable analytical tool to study oxidative stress-related diseases and experimental inflammatory conditions, and also in the evaluation of various dietary antioxidants, as well as drugs with radical-scavenging properties. However, assessment of isoprostanes in plasma or urine does not necessarily reflect any specific tissue damage, nor does it provide information on the oxidation of lipids other than arachidonic acid

Association of 25-hydroxyvitamin D deficiency with NT-pro BNP levels in patients with acute myocardial infarction: a cross-sectional analysis

<p>Abstract</p> <p>Background</p> <p>Nutritional vitamin D deficiency is an emerging risk factor for acute myocardial infarction (AMI) and heart failure. The association of 25-hydroxyvitamin D levels with N-terminal pro B-type natriuretic peptide (NT-proBNP), a robust prognostic marker for post-AMI mortality and heart failure, is unknown and could illuminate a potential pathway for adverse outcomes among post-AMI patients with 25-hydroxyvitamin D deficiency.</p> <p>Methods</p> <p>In a cross-sectional analysis, we studied 238 AMI patients from 21 U.S. centers to test the association of nutritional vitamin D (25-hydroxyvitamin D [25(OH)D]) deficiency with NT-proBNP levels. Levels of 25(OH)D levels were categorized as normal (≥30 ng/mL), insufficient (>20 - <30 ng/mL), deficient (>10 - ≤20 ng/mL), or severely deficient (≤10 ng/mL).</p> <p>Results</p> <p>Low 25(OH)D levels were found in 95.7% of AMI patients. No significant trends for higher mean baseline log NT-proBNP levels in severely deficient (6.9 ± 1.3 pg/mL), deficient (6.9 ± 1.2 pg/mL), and insufficient (6.9 ± 0.9 pg/ml) groups were observed as compared with patients having normal (6.1 ± 1.7 pg/mL) levels, <it>P </it>= 0.17. Findings were similar in the subset of patients who had follow-up NT-proBNP levels drawn at one month. In multivariate regression modeling, after adjusting for multiple covariates, 25(OH)D was not associated with NT-proBNP.</p> <p>Conclusions</p> <p>Potential associations between nutritional vitamin D deficiency and prognosis in the setting of AMI are unlikely to be mediated through NT-proBNP pathways. Future studies should examine other mechanisms, such as inflammation and vascular calcification, by which 25(OH)D deficiency could mediate adverse outcomes post-AMI.</p

The Concept of Transparency in International Relations: towards a critical approach

Transparency is an important concept in International Relations. The possibility of realizing transparency in practice operates as a central analytical axis defining distinct positions on core theoretical problems within the field, from the security dilemma to the function of international institutions and beyond. As a political practice the pursuit of transparent governance is a dominant feature of global politics, promoted by a wide range of actors across a vast range of issue areas, from nuclear proliferation to Internet governance to the politics of foreign aid. Yet, despite its importance, precisely what transparency means or how the concept is understood is frequently ill-defined by academics and policy-makers alike. As a result, the epistemological and ontological underpinnings of approaches to transparency in IR often sit in tension with their wider theoretical commitments. This article will examine the three primary understandings of transparency used in IR in order to unpack these commitments. It finds that while transparency is often explicitly conceptualized as a property of information, particularly within rationalist scholarship, this understanding rests upon an unarticulated set of sociological assumptions. This analysis suggests that conceptualizing ‘transparency-as-information’ without a wider sociology of knowledge production is highly problematic, potentially obscuring our ability to recognize transparent practices in global governance. Understanding transparency as dialogue, as a social practice rooted in shared cognitive capacities and epistemic frameworks, provides a firmer analytical ground from which to examine transparency in International Relations

The do's, don't and don't knows of supporting transition to more independent practice

Introduction: Transitions are traditionally viewed as challenging for clinicians. Throughout medical career pathways, clinicians need to successfully navigate successive transitions as they become progressively more independent practitioners. In these guidelines, we aim to synthesize the evidence from the literature to provide guidance for supporting clinicians in their development of independence, and highlight areas for further research. Methods: Drawing upon D3 method guidance, four key themes universal to medical career transitions and progressive independence were identified by all authors through discussion and consensus from our own experience and expertise: workplace learning, independence and responsibility, mentoring and coaching, and patient perspectives. A scoping review of the literature was conducted using Medline database searches in addition to the authors’ personal archives and reference snowballing searches. Results: 387 articles were identified and screened. 210 were excluded as not relevant to medical transitions (50 at title screen; 160 at abstract screen). 177 full-text articles were assessed for eligibility; a further 107 were rejected (97 did not include career transitions in their study design; 10 were review articles; the primary references of these were screened for inclusion). 70 articles were included of which 60 provided extractable data for the final qualitative synthesis. Across the four key themes, seven do’s, two don’ts and seven don’t knows were identified, and the strength of evidence was graded for each of these recommendations. Conclusion: The two strongest messages arising from current literature are first, transitions should not be viewed as one moment in time: career trajectories are a continuum with valuable opportunities for personal and professional development throughout. Second, learning needs to be embedded in practice and learners provided with authentic and meaningful learning opportunities. In this paper, we propose evidence-based guidelines aimed at facilitating such transitions through the fostering of progressive independence

Genetic Variations in IL28B and Allergic Disease in Children

Environmental changes affecting the relationship between the developing immune system and microbial exposure have been implicated in the epidemic rise of allergic disease in developed countries. While early developmental differences in T cell function are well-recognised, there is now emerging evidence that this is related to developmental differences in innate immune function. In this study we sought to examine if differences associated with innate immunity contribute to the altered immune programming recognised in allergic children. Here, we describe for the first time, the association of carriage of the T allele of the tagging single nucleotide polymorphism rs12979860 3 kb upstream of IL28B, encoding the potent innate immune modulator type III interferon lambda (IFN-λ3), and allergy in children (p = 0.004; OR 4.56). Strikingly, the association between rs12979860 genotype and allergic disease is enhanced in girls. Furthermore, carriage of the T allele at rs12979860 correlates with differences in the pro-inflammatory profile during the first five years of life suggesting this contributes to the key differences in subsequent innate immune development in children who develop allergic disease. In the context of rising rates of disease, these immunologic differences already present at birth imply very early interaction between genetic predisposition and prenatal environmental influences