Mammographic density adds accuracy to both the Tyrer-Cuzick and Gail breast cancer risk models in a prospective UK screening cohort

This work was supported by the National Institute for Health Research (NIHR) and Genesis Breast Cancer Prevention Appeal (references GA10-033 and GA13-006). This article presents independent research funded by the NIHR under its Programme Grants for Applied Research (grant RP-PG-0707-10031). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The authors also acknowledge the support of Medical Research Council Health eResearch Centre grant MR/K006665/1

Imaging the Impact of Prenatal Alcohol Exposure on the Structure of the Developing Human Brain

Prenatal alcohol exposure has numerous effects on the developing brain, including damage to selective brain structure. We review structural magnetic resonance imaging (MRI) studies of brain abnormalities in subjects prenatally exposed to alcohol. The most common findings include reduced brain volume and malformations of the corpus callosum. Advanced methods have been able to detect shape, thickness and displacement changes throughout multiple brain regions. The teratogenic effects of alcohol appear to be widespread, affecting almost the entire brain. The only region that appears to be relatively spared is the occipital lobe. More recent studies have linked cognition to the underlying brain structure in alcohol-exposed subjects, and several report patterns in the severity of brain damage as it relates to facial dysmorphology or to extent of alcohol exposure. Future studies exploring relationships between brain structure, cognitive measures, dysmorphology, age, and other variables will be valuable for further comprehending the vast effects of prenatal alcohol exposure and for evaluating possible interventions

Blood cell gene expression associated with cellular stress defense is modulated by antioxidant-rich food in a randomised controlled clinical trial of male smokers

Background Plant-based diets rich in fruit and vegetables can prevent development of several chronic age-related diseases. However, the mechanisms behind this protective effect are not elucidated. We have tested the hypothesis that intake of antioxidant-rich foods can affect groups of genes associated with cellular stress defence in human blood cells. Trial registration number: NCT00520819 http://clinicaltrials.gov. Methods In an 8-week dietary intervention study, 102 healthy male smokers were randomised to either a diet rich in various antioxidant-rich foods, a kiwifruit diet (three kiwifruits/d added to the regular diet) or a control group. Blood cell gene expression profiles were obtained from 10 randomly selected individuals of each group. Diet-induced changes on gene expression were compared to controls using a novel application of the gene set enrichment analysis (GSEA) on transcription profiles obtained using Affymetrix HG-U133-Plus 2.0 whole genome arrays. Results Changes were observed in the blood cell gene expression profiles in both intervention groups when compared to the control group. Groups of genes involved in regulation of cellular stress defence, such as DNA repair, apoptosis and hypoxia, were significantly upregulated (GSEA, FDR q-values < 5%) by both diets compared to the control group. Genes with common regulatory motifs for aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (AhR/ARNT) were upregulated by both interventions (FDR q-values < 5%). Plasma antioxidant biomarkers (polyphenols/carotenoids) increased in both groups. Conclusions The observed changes in the blood cell gene expression profiles suggest that the beneficial effects of a plant-based diet on human health may be mediated through optimization of defence processes

Increased peri-ductal collagen micro-organization may contribute to raised mammographic density

BACKGROUND: High mammographic density is a therapeutically modifiable risk factor for breast cancer. Although mammographic density is correlated with the relative abundance of collagen-rich fibroglandular tissue, the causative mechanisms, associated structural remodelling and mechanical consequences remain poorly defined. In this study we have developed a new collaborative bedside-to-bench workflow to determine the relationship between mammographic density, collagen abundance and alignment, tissue stiffness and the expression of extracellular matrix organising proteins. METHODS: Mammographic density was assessed in 22 post-menopausal women (aged 54–66 y). A radiologist and a pathologist identified and excised regions of elevated non-cancerous X-ray density prior to laboratory characterization. Collagen abundance was determined by both Masson’s trichrome and Picrosirius red staining (which enhances collagen birefringence when viewed under polarised light). The structural specificity of these collagen visualisation methods was determined by comparing the relative birefringence and ultrastructure (visualised by atomic force microscopy) of unaligned collagen I fibrils in reconstituted gels with the highly aligned collagen fibrils in rat tail tendon. Localised collagen fibril organisation and stiffness was also evaluated in tissue sections by atomic force microscopy/spectroscopy and the abundance of key extracellular proteins was assessed using mass spectrometry. RESULTS: Mammographic density was positively correlated with the abundance of aligned periductal fibrils rather than with the abundance of amorphous collagen. Compared with matched tissue resected from the breasts of low mammographic density patients, the highly birefringent tissue in mammographically dense breasts was both significantly stiffer and characterised by large (>80 μm long) fibrillar collagen bundles. Subsequent proteomic analyses not only confirmed the absence of collagen fibrosis in high mammographic density tissue, but additionally identified the up-regulation of periostin and collagen XVI (regulators of collagen fibril structure and architecture) as potential mediators of localised mechanical stiffness. CONCLUSIONS: These preliminary data suggest that remodelling, and hence stiffening, of the existing stromal collagen microarchitecture promotes high mammographic density within the breast. In turn, this aberrant mechanical environment may trigger neoplasia-associated mechanotransduction pathways within the epithelial cell population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-015-0664-2) contains supplementary material, which is available to authorized users

Darwinism, organizational evolution and survival: key challenges for future research

How do social organizations evolve? How do they adapt to environmental pressures? What resources and capabilities determine their survival within dynamic competition? Charles Darwin’s seminal work The Origin of Species (1859) has provided a significant impact on the development of the management and organization theory literatures on organizational evolution. This article introduces the JMG Special Issue focused on Darwinism, organizational evolution and survival. We discuss key themes in the organizational evolution research that have emerged in recent years. These include the increasing adoption of the co-evolutionary approach, with a particular focus on the definition of appropriate units of analysis, such as routines, and related challenges associated with exploring the relationship between co-evolution, re-use of knowledge, adaptation, and exaptation processes. We then introduce the three articles that we have finally accepted in this Special Issue after an extensive, multi-round, triple blind-review process. We briefly outline how each of these articles contributes to understanding among scholars, practitioners and policy makers of the continuous evolutionary processes within and among social organizations and systems

Assessing the quality of cardiac rehabilitation programs by measuring adherence to the Australian quality indicators

Background: Every year, over 65,000 Australians experience an acute coronary syndrome (ACS) and around one-third occur in people with prior coronary heart disease. Cardiac rehabilitation (CR) aims to prevent a repeat ACS by supporting patients’ return to an active and fulfilling lifestyle. CR programs are efficacious, but audits of clinical practice show variability of program delivery, which may compromise patient outcomes. Core components, quality indicators and accreditation of programs have been introduced internationally to increase program standardisation. With Australian quality indicators (QIs) for cardiac rehabilitation recently introduced, we aimed to conduct a survey in one state of Australia to assess the extent to which programs adhere to the measurement of QIs comparing country, metropolitan, telephone and face to face programs. Methods: A cross- sectional survey design with face validity testing was used to formulate questions to evaluate cardiac rehabilitation program and personnel characteristics and QI adherence. Between October 2020- December 2021, 23 cardiac rehabilitation programs across country and metropolitan areas were invited to participate. Quality improvement was defined as adherence to the Australian Quality Indicators, and we developed an objective score to calculate program performance categorised by quartiles. Significance of CR completion and time to enrolment between program type (telephone versus face to face) and location (country versus metropolitan were compared using Pearson’s Chi-square and Mann–Whitney U tests. Results: Among the 23 CR programs, 15 were country and 8 metropolitan-based and 22 were face to face and 1 telephone-based. Median wait time from discharge was 27.0 days, (interquartile range 19.3–46.0) across all programs and country completions of enrolled were 76.9% versus metropolitan 56.5%, p<0.001 and telephone versus face to face 92.9% versus 59.6% p<0.001. Pre-program QI adherence was higher than post program for depression, medication adherence, health-related quality of life and comprehensive re-assessment. Seventy four percent of programs were ranked at a medium level of performance (mean score: 11.4/16, SD±0.79). Conclusions: A survey of 23 cardiac rehabilitation programs, showed variability in adherence to measurement of the Australian Cardiovascular and Rehabilitation Association and Australian Heart Foundation Cardiac Rehabilitation Quality Indicators.C. M. Astley, A. Beleigoli, R. Tavella, J. Hendriks, C. Gallagher, R. Tirimacco, G. Wilson, T. Barry, and R. A. Clar