Which Test Is Best? A Cluster-Randomized Controlled Trial of a Risk Calculator and Recommendations on Colorectal Cancer Screening Behaviour in General Practice

Introduction: This cluster-randomized controlled trial aimed to assess the effect of the "Which test is best?"tool on risk-appropriate screening (RAS) and colorectal cancer (CRC) screening uptake. Methods: General practices in Sydney and Melbourne, Australia, and a random sub-sample of 460 patients (aged 25-74 years) per practice were invited by post. Clusters were computer randomized independently of the researchers to an online CRC risk calculator with risk-based recommendations versus usual care. Primary and secondary outcomes were RAS and screening uptake via self-reported 5-year screening behaviour after 12 months follow-up. The usual care group (UCG) also self-reported 5-year CRC screening behaviour at 12 month post-randomization. Results: Fifty-six practices were randomized (27 to the intervention and 29 to the control, 55 practices participated) with 818 intervention and 677 controls completing the primary outcome measure. The intervention significantly increased RAS in high-risk participants compared with UCG (80.0% vs. 64.0%, respectively; OR = 3.14, 95% CI: 1.25-7.96) but not in average-risk (44.9% vs. 49.5%, respectively; OR = 0.97, 95% CI: 0.99-1.12) or moderate-risk individuals (67.9% vs. 81.1%, respectively; OR = 0.40, 95% CI: 0.12-1.33). Faecal occult blood testing uptake over 12 months was increased compared with the UCG (24.9% vs. 15.1%; adjusted OR = 1.66, 95% CI: 1.24-2.22), and there was a non-significant increase in colonoscopies during the same period (16.6% vs. 12.2%; adjusted OR = 1.42, 95% CI: 0.97-2.08). Conclusion: An online CRC risk calculator with risk-based screening recommendations increased RAS in high-risk participants and improved screening uptake overall within a 12-month follow-up period. Such tools may be useful for facilitating the uptake of risk-based screening guidelines

Undefined familial colorectal cancer and the role of pleiotropism in cancer susceptibility genes.

Although family history is a major risk factor for colorectal cancer (CRC) a genetic diagnosis cannot be obtained in over 50 % of familial cases when screened for known CRC cancer susceptibility genes. The genetics of undefined-familial CRC is complex and recent studies have implied additional clinically actionable mutations for CRC in susceptibility genes for other cancers. To clarify the contribution of non-CRC susceptibility genes to undefined-familial CRC we conducted a mutational screen of 114 cancer susceptibility genes in 847 patients with early-onset undefined-familial CRC and 1609 controls by analysing high-coverage exome sequencing data. We implemented American College of Medical Genetics and Genomics standards and guidelines for assigning pathogenicity to variants. Globally across all 114 cancer susceptibility genes no statistically significant enrichment of likely pathogenic variants was shown (6.7 % cases 57/847, 5.3 % controls 85/1609; P = 0.15). Moreover there was no significant enrichment of mutations in genes such as TP53 or BRCA2 which have been proposed for clinical testing in CRC. In conclusion, while we identified genes that may be considered interesting candidates as determinants of CRC risk warranting further research, there is currently scant evidence to support a role for genes other than those responsible for established CRC syndromes in the clinical management of familial CRC

Uncovering Tacit Knowledge: A Pilot Study to Broaden the Concept of Knowledge in Knowledge Translation

BACKGROUND: All sectors in health care are being asked to focus on the knowledge-to-practice gap, or knowledge translation, to increase service effectiveness. A social interaction approach to knowledge translation assumes that research evidence becomes integrated with previously held knowledge, and practitioners build on and co-create knowledge through mutual interactions. Knowledge translation strategies for public health have not provided anticipated positive changes in evidence-based practice, possibly due in part to a narrow conceptualization of knowledge. More work is needed to understand the role of tacit knowledge in decision-making and practice. This pilot study examined how health practitioners applied tacit knowledge in public health program planning and implementation. METHODS: This study used a narrative approach, where teams from two public health units in Ontario, Canada were conveniently selected. Respondents participated in individual interviews and focus groups at each site. Questions were designed to understand the role of tacit knowledge as it related to the program planning process. Data were analyzed through a combination of content analysis and thematic comparison. RESULTS: The findings highlighted two major aspects of knowledge that arose: the use of tacit knowledge and the integration of tacit and explicit knowledge. Tacit knowledge included: past experiences, organization-specific knowledge, community contextual knowledge, and the recognition of the tacit knowledge of others. Explicit knowledge included: research literature, the Internet, popular magazines, formal assessments (surveys and interviews), legislation and regulations. Participants sometimes deliberately combined tacit and explicit knowledge sources in planning. CONCLUSIONS: This pilot demonstrated that front-line public health workers draw upon both tacit knowledge and explicit knowledge in their everyday lived reality. Further, tacit knowledge plays an important role in practitioners\u27 interpretation and implementation of explicit research findings. This indicates a need to broaden the scope of knowledge translation to include other forms of knowledge beyond explicit knowledge acquired through research. Strategies that recognize and support the use of tacit knowledge, such as communities of practice or networks, may be important components of a comprehensive approach to knowledge translation. This study provides support for further investigation of the role of tacit knowledge in the planning and delivery of effective public health services

Monte Carlo investigations of the effect of beam divergence on thick, segmented crystalline scintillators for radiotherapy imaging

The use of thick, segmented scintillators in electronic portal imagers offers the potential for significant improvement in x-ray detection efficiency compared to conventional phosphor screens. Such improvement substantially increases the detective quantum efficiency (DQE), leading to the possibility of achieving soft-tissue visualization at clinically practical (i.e. low) doses using megavoltage (MV) cone-beam computed tomography. While these DQE increases are greatest at zero spatial frequency, they are diminished at higher frequencies as a result of degradation of spatial resolution due to lateral spreading of secondary radiation within the scintillator—an effect that is more pronounced for thicker scintillators. The extent of this spreading is even more accentuated for radiation impinging the scintillator at oblique angles of incidence due to beam divergence. In this paper, Monte Carlo simulations of radiation transport, performed to investigate and quantify the effects of beam divergence on the imaging performance of MV imagers based on two promising scintillators (BGO and CsI:Tl), are reported. In these studies, 10–40 mm thick scintillators, incorporating low-density polymer, or high-density tungsten septal walls, were examined for incident angles corresponding to that encountered at locations up to ~15 cm from the central beam axis (for an imager located 130 cm from a radiotherapy x-ray source). The simulations demonstrate progressively more severe spatial resolution degradation (quantified in terms of the effect on the modulation transfer function) as a function of increasing angle of incidence (as well as of the scintillator thickness). Since the noise power behavior was found to be largely independent of the incident angle, the dependence of the DQE on the incident angle is therefore primarily determined by the spatial resolution. The observed DQE degradation suggests that 10 mm thick scintillators are not strongly affected by beam divergence for detector areas up to ~30 × 30 cm2. For thicker scintillators, the area that is relatively unaffected is significantly reduced, requiring a focused scintillator geometry in order to preserve spatial resolution, and thus DQE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85404/1/pmb10_13_006.pd

The school environment and adolescent physical activity and sedentary behaviour : A mixed-studies systematic review

There is increasing academic and policy interest in interventions aiming to promote young people's health by ensuring that the school environment supports healthy behaviours. The purpose of this review was to summarize the current evidence on school-based policy, physical and social-environmental influences on adolescent physical activity and sedentary behaviour. Electronic databases were searched to identify studies that (1) involved healthy adolescents (11-18years old), (2) investigated school-environmental influences and (3) reported a physical activity and/or sedentary behaviour outcome or theme. Findings were synthesized using a non-quantitative synthesis and thematic analysis. Ninety-three papers of mixed methodological quality were included. A range of school-based policy (e.g. break time length), physical (e.g. facilities) and social-environmental (e.g. teacher behaviours) factors were associated with adolescent physical activity, with limited research on sedentary behaviour. The mixed-studies synthesis revealed the importance of specific activity settings (type and location) and intramural sport opportunities for all students. Important physical education-related factors were a mastery-oriented motivational climate and autonomy supportive teaching behaviours. Qualitative evidence highlighted the influence of the wider school climate and shed light on complexities of the associations observed in the quantitative literature. This review identifies future research needs and discusses potential intervention approaches to be considered

Effects of Impurity Content on the Sintering Characteristics of Plasma-Sprayed Zirconia

Yttria-stabilized zirconia powders, containing different levels of SiO2 and Al2O3, have been plasma sprayed onto metallic substrates. The coatings were detached from their substrates and a dilatometer was used to monitor the dimensional changes they exhibited during prolonged heat treatments. It was found that specimens containing higher levels of silica and alumina exhibited higher rates of linear contraction, in both in-plane and through-thickness directions. The in-plane stiffness and the through-thickness thermal conductivity were also measured after different heat treatments and these were found to increase at a greater rate for specimens with higher impurity (silica and alumina) levels. Changes in the pore architecture during heat treatments were studied using Mercury Intrusion Porosimetry (MIP). Fine scale porosity (<_50 nm) was found to be sharply reduced even by relatively short heat treatments. This is correlated with improvements in inter-splat bonding and partial healing of intra-splat microcracks, which are responsible for the observed changes in stiffness and conductivity, as well as the dimensional changes

Specialized dynamical properties of promiscuous residues revealed by simulated conformational ensembles

The ability to interact with different partners is one of the most important features in proteins. Proteins that bind a large number of partners (hubs) have been often associated with intrinsic disorder. However, many examples exist of hubs with an ordered structure, and evidence of a general mechanism promoting promiscuity in ordered proteins is still elusive. An intriguing hypothesis is that promiscuous binding sites have specific dynamical properties, distinct from the rest of the interface and pre-existing in the protein isolated state. Here, we present the first comprehensive study of the intrinsic dynamics of promiscuous residues in a large protein data set. Different computational methods, from coarse-grained elastic models to geometry-based sampling methods and to full-atom Molecular Dynamics simulations, were used to generate conformational ensembles for the isolated proteins. The flexibility and dynamic correlations of interface residues with a different degree of binding promiscuity were calculated and compared considering side chain and backbone motions, the latter both on a local and on a global scale. The study revealed that (a) promiscuous residues tend to be more flexible than nonpromiscuous ones, (b) this additional flexibility has a higher degree of organization, and (c) evolutionary conservation and binding promiscuity have opposite effects on intrinsic dynamics. Findings on simulated ensembles were also validated on ensembles of experimental structures extracted from the Protein Data Bank (PDB). Additionally, the low occurrence of single nucleotide polymorphisms observed for promiscuous residues indicated a tendency to preserve binding diversity at these positions. A case study on two ubiquitin-like proteins exemplifies how binding promiscuity in evolutionary related proteins can be modulated by the fine-tuning of the interface dynamics. The interplay between promiscuity and flexibility highlighted here can inspire new directions in protein-protein interaction prediction and design methods. © 2013 American Chemical Society