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Background Previous screening interventions have demonstrated a series of features related to social determinants which have increased uptake in targeted populations, including the assessment of health beliefs and barriers to screening attendance as part of intervention development. Many studies cite the use of theory to identify methods of behaviour change, but fail to describe in detail how theoretical constructs are transformed into intervention content. The aim of this study was to use data from a qualitative exploration of cervical screening in women over 50 in the UK as the basis of intervention co-design with stakeholders using behavioural change frameworks. We describe the identification of behavioural mechanisms from qualitative data, and how these were used to develop content for a service-user leaflet and a video animation for practitioner training. The interventions aimed to encourage sustained commitment to cervical screening among women over 50, and to increase sensitivity to age-related problems in screening among primary care practitioners. Methods Secondary coding of a qualitative data set to extract barriers and facilitators of cervical screening attendance. Barrier and facilitator statements were categorised using the Theoretical Domains Framework (TDF) to identify relevant behaviour change techniques (BCTs). Key TDF domains and associated BCTs were presented in stakeholder focus groups to guide the design of intervention content and mode of delivery. Results Behavioural determinants relating to attendance clustered under three domains: beliefs about consequences, emotion and social influences, which mapped to three BCTs respectively: (1) persuasive communication/information provision; (2) stress management; (3) role modelling and encouragement. Service-user stakeholders translated these into three pragmatic intervention components: (i) addressing unanswered questions, (ii) problem-solving practitioner challenges and (iii) peer group communication. Based on (ii), practitioner stakeholders developed a call to action in three areas – clinical networking, history-taking, and flexibility in screening processes. APEASE informed modes of delivery (a service-user leaflet and a cartoon animation for practitioners). Conclusion The application of the TDF to qualitative data can provide an auditable protocol for the translation of qualitative data into intervention content.

Glutaraldehyde-fixed bovine pericardium is currently the most popular biomaterial utilized in the creation of bioprosthetic heart valves. However, recent studies indicate that glutaraldehyde fixation results in calcification and structural valve deterioration, limiting the longevity of bioprosthetic heart valves. Additionally, glutaraldehyde fixation renders the tissue incompatible with constructive recipient cellular repopulation, remodeling and growth. Use of unfixed xenogeneic biomaterials devoid of antigenic burden has potential to overcome the limitations of current glutaraldehyde-fixed biomaterials. Heart valves undergo billion cycles of opening and closing throughout the patient's lifetime. Therefore, understanding the response of unfixed tissues to cyclic loading is crucial to these in a heart valve leaflet configuration. In this manuscript we quantify the effect of cyclic deformation on cycle dependent strain, structural, compositional and mechanical properties of fixed and unfixed tissues. Glutaraldehyde-fixed bovine pericardium underwent marked cyclic dependent strain, resulting from significant changes in structure, composition and mechanical function of the material. Conversely, unfixed bovine pericardium underwent minimal strain and maintained its structure, composition and mechanical integrity. This manuscript demonstrates that unfixed bovine pericardium can withstand cyclic deformations equivalent to 6 months of in vivo heart valve leaflet performance.

Oppositely charged polymer–surfactant complexes are frequently explored as a function of phase space defined by the charge ratio Z, (where Z = [+polymer]/[−surfactant]), commonly accessed through the surfactant concentration. Tuning the phase behaviour and related properties of these complexes is an important tool for optimising commercial formulations; hence, understanding the relationship between Z and bulk properties is pertinent. Here, within a homologous series of cationic hydroxyethyl cellulose (cat-HEC) polymers with minor perturbations in the degree of side chain charge modification, phase space is instead explored through [+polymer] at fixed Cpolymer. The nanostructures were characterised by small-angle neutron scattering (SANS) in D2O solutions and in combination with the oppositely charged surfactant sodium dodecylsulfate (h- or d-SDS). Scattering consistent with thin rods with an average radius of ∼7.7 Å and length of ∼85 Å was observed for all cat-HEC polymers and no significant interactions were shown between the neutral HEC polymer and SDS (CSDS < CMC). For the charge-modified polymers, interactions with SDS were evident and the radius of the formed complexes grew up to ∼15 Å with increasing Z. This study demonstrates a novel approach in which the Z phase space of oppositely charged polymer–surfactant complexes can be controlled at fixed concentrations.

Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be ‘passengers’ that do not contribute to oncogenesis. However, there was evidence for ‘driver’ mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated. Cancer gene haul Over 350 cancer-causing genes have been identified by established techniques such as mapping, bioassay and by identifying plausible biological candidates. The availability of the human genome sequence now means that large-scale sequencing studies can uncover many more candidate cancer genes. Protein kinase enzymes are key to many regulatory processes and their dysfunction is a common trigger for tumours. So a sample of 518 kinases associated with more than 200 different cancers was chosen for a major sequencing effort. The study reveals more than 1, 000 previously unknown mutations linked to tumour formation — some as 'passengers' that don't contribute to cancer formation, but over 100 of them as 'driver' mutations that do contribute to disease development. As well as revealing cancer-causing defects, gene family studies like this can uncover new targets for molecular diagnostics and therapeutics. 518 protein kinase genes in the human genome have been sequenced in a large sample of tumours, providing a global view of the patterns of mutations found and the variations in the number and type of mutations between individual tumours.

Cyphochilus beetle scales are amongst the brightest structural whites in nature, being highly opacifying whilst extremely thin. However, the formation mechanism for the voided intra-scale structure is unknown. Here we report 3D x-ray nanotomography data for the voided chitin networks of intact white scales of Cyphochilus and Lepidiota stigma . Chitin-filling fractions are found to be 31 ± 2% for Cyphochilus and 34 ± 1% for Lepidiota stigma , indicating previous measurements overestimated their density. Optical simulations using finite-difference time domain for the chitin morphologies and simulated Cahn-Hilliard spinodal structures show excellent agreement. Reflectance curves spanning filling fraction of 5-95% for simulated spinodal structures, pinpoint optimal whiteness for 25% chitin filling. We make a simulacrum from a polymer undergoing a strong solvent quench, resulting in highly reflective (~94%) white films. In-situ X-ray scattering confirms the nanostructure is formed through spinodal decomposition phase separation. We conclude that the ultra-white beetle scale nanostructure is made via liquid–liquid phase separation. White beetle scales strongly scatter white light, whilst being very thin. Here, the authors measured the internal scale nanostructure for the beetles, Cyphochilus and L. stigma , and demonstrate that the optical structure can be simulated using liquid–liquid phase separation nanostructures, pointing to this as the formation mechanism.

Background Abbreviated breast MRI (abMRI) is being introduced in breast screening trials and clinical practice, particularly for women with dense breasts. Upscaling abMRI provision requires the workforce of mammogram readers to learn to effectively interpret abMRI. The purpose of this study was to examine the diagnostic accuracy of mammogram readers to interpret abMRI after a single day of standardised small-group training and to compare diagnostic performance of mammogram readers experienced in full-protocol breast MRI (fpMRI) interpretation (Group 1) with that of those without fpMRI interpretation experience (Group 2). Methods Mammogram readers were recruited from six NHS Breast Screening Programme sites. Small-group hands-on workstation training was provided, with subsequent prospective, independent, blinded interpretation of an enriched dataset with known outcome. A simplified form of abMRI (first post-contrast subtracted images (FAST MRI), displayed as maximum-intensity projection (MIP) and subtracted slice stack) was used. Per-breast and per-lesion diagnostic accuracy analysis was undertaken, with comparison across groups, and double-reading simulation of a consecutive screening subset. Results 37 readers (Group 1: 17, Group 2: 20) completed the reading task of 125 scans (250 breasts) (total = 9250 reads). Overall sensitivity was 86% (95% confidence interval (CI) 84–87%; 1776/2072) and specificity 86% (95%CI 85–86%; 6140/7178). Group 1 showed significantly higher sensitivity (843/952; 89%; 95%CI 86–91%) and higher specificity (2957/3298; 90%; 95%CI 89–91%) than Group 2 (sensitivity = 83%; 95%CI 81–85% (933/1120) p < 0.0001; specificity = 82%; 95%CI 81–83% (3183/3880) p < 0.0001). Inter-reader agreement was higher for Group 1 (kappa = 0.73; 95%CI 0.68–0.79) than for Group 2 (kappa = 0.51; 95%CI 0.45–0.56). Specificity improved for Group 2, from the first 55 cases (81%) to the remaining 70 (83%) ( p = 0.02) but not for Group 1 (90–89% p = 0.44), whereas sensitivity remained consistent for both Group 1 (88–89%) and Group 2 (83–84%). Conclusions Single-day abMRI interpretation training for mammogram readers achieved an overall diagnostic performance within benchmarks published for fpMRI but was insufficient for diagnostic accuracy of mammogram readers new to breast MRI to match that of experienced fpMRI readers. Novice MRI reader performance improved during the reading task, suggesting that additional training could further narrow this performance gap.