New relationships between breast microcalcifications and cancer.

PublishedJournal ArticleResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from Cancer Research UK via the DOI in this record.BACKGROUND: Breast microcalcifications are key diagnostically significant radiological features for localisation of malignancy. This study explores the hypothesis that breast calcification composition is directly related to the local tissue pathological state. METHODS: A total of 236 human breast calcifications from 110 patients were analysed by mid-Fouries transform infrared (FTIR) spectroscopy from three different pathology types (112 invasive carcinoma (IC), 64 in-situ carcinomas and 60 benign). The biochemical composition and the incorporation of carbonate into the hydroxyapatite lattice of the microcalcifications were studied by infrared microspectroscopy. This allowed the spectrally identified composition to be directly correlated with the histopathology grading of the surrounding tissue. RESULTS: The carbonate content of breast microcalcifications was shown to significantly decrease when progressing from benign to malignant disease. In this study, we report significant correlations (P<0.001) between microcalcification chemical composition (carbonate content and protein matrix : mineral ratios) and distinct pathology grades (benign, in-situ carcinoma and ICs). Furthermore, a significant correlation (P<0.001) was observed between carbonate concentrations and carcinoma in-situ sub-grades. Using the two measures of pathology-specific calcification composition (carbonate content and protein matrix : mineral ratios) as the inputs to a two-metric discriminant model sensitivities of 79, 84 and 90% and specificities of 98, 82 and 96% were achieved for benign, ductal carcinoma in situ and invasive malignancies, respectively. CONCLUSIONS: We present the first demonstration of a direct link between the chemical nature of microcalcifications and the grade of the pathological breast disease. This suggests that microcalcifications have a significant association with cancer progression, and could be used for future objective analytical classification of breast pathology. A simple two-metric model has been demonstrated, more complex spectral analysis may yeild greater discrimination performance. Furthermore there appears to be a sequential progression of calcification composition.Professor Nicholas Stone is supported by a National Institute of Health Research (NIHR) Career Scientist (Senior) Research Fellowship. Rebecca Baker performed the study, performed the data analysis and wrote the paper. Keith Rogers designed and supervised the study and wrote the paper. Neil Shepherd provided expert histopathology support and discussion. Nicholas Stone designed and supervised the study and wrote the paper. The authors declare no conflicts of interest. Ethical approval for this study was provided by the Gloucestershire Local Research Ethics Committee, UK

X-ray diffraction from bone employing annular and semi-annular beams

This is the final version of the article. Available from the publisher via the DOI in this record.There is a compelling need for accurate, low cost diagnostics to identify osteo-tissues that are associated with a high risk of fracture within an individual. To satisfy this requirement the quantification of bone characteristics such as 'bone quality' need to exceed that provided currently by densitometry. Bone mineral chemistry and microstructure can be determined from coherent x-ray scatter signatures of bone specimens. Therefore, if these signatures can be measured, in vivo, to an appropriate accuracy it should be possible by extending terms within a fracture risk model to improve fracture risk prediction.In this preliminary study we present an examination of a new x-ray diffraction technique that employs hollow annular and semi-annular beams to measure aspects of 'bone quality'. We present diffractograms obtained with our approach from ex vivo bone specimens at Mo Kα and W Kα energies. Primary data is parameterized to provide estimates of bone characteristics and to indicate the precision with which these can be determined.We acknowledge gratefully the funding provided by the UK Engineering and Physical Sciences Research Council (EPSRC) grant number EP/K020196/

Sporadic absorption tomography using a conical shell X-ray beam

We demonstrate tomography by measuring a sporadic sequence of ring shaped projections collected during a translational scan. We show that projections using 10% sampling may be used to construct optical sections with peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM) of the order of 40 dB and 0.9, respectively. This relatively small degradation in image fidelity was achieved for a 90% potential reduction in X-ray dose coupled with a reduction in scan time. Our approach is scalable in both X-ray energy and inspection volume. A driver for our method is to complement previously reported conical shell beam techniques concerning the measurement of diffracted flux for structural analysis. This work is of great relevance to time critical analytical scanning applications in security screening, process control and diagnostic imaging

Energy-dispersive X-ray diffraction using an annular beam

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.We demonstrate material phase identification by measuring polychromatic diffraction spots from samples at least 20 mm in diameter and up to 10 mm thick with an energy resolving point detector. Within our method an annular X-ray beam in the form of a conical shell is incident with its symmetry axis normal to an extended polycrystalline sample. The detector is configured to receive diffracted flux transmitted through the sample and is positioned on the symmetry axis of the annular beam. We present the experiment data from a range of different materials and demonstrate the acquisition of useful data with sub-second collection times of 0.5 s; equating to 0.15 mAs. Our technique should be highly relevant in fields that demand rapid analytical methods such as medicine, security screening and non-destructive testing.We acknowledge gratefully the funding provided by the UK Engineering and Physical Sciences Research Council (EPSRC) grant number EP/K020196/1

The Link between Dengue Incidence and El Niño Southern Oscillation

Pejman Rohani discusses a new study that examined the dynamic relationship between climate variables and dengue incidence in Thailand, Mexico, and Puerto Rico

Study protocol for a real-world evaluation of an integrated child and family health hub for migrant and refugee women

Introduction Continuity of child and family healthcare is vital for optimal child health and development for developmentally vulnerable children. Migrant and refugee communities are often at-risk of poor health outcomes, facing barriers to health service attendance including cultural, language, limited health literacy, discrimination and unmet psychosocial needs. 'Integrated health-social care hubs' are physical hubs where health and social services are co-located, with shared referral pathways and care navigation. Aim Our study will evaluate the impact, implementation and cost-benefit of the First 2000 Days Care Connect (FDCC) integrated hub model for pregnant migrant and refugee women and their infants. Materials and methods This study has three components. Component 1 is a non-randomised controlled trial to compare the FDCC model of care with usual care. This trial will allocate eligible women to intervention and control groups based on their proximity to the Hub sites. Outcome measures include: the proportion of children attending child and family health (CFH) nurse services and completing their CFH checks to 12 months of age; improved surveillance of growth and development in children up to 12 months, post partum; improved breastfeeding rates; reduced emergency department presentations; and improved maternal well-being. These will be measured using linked medical record data and surveys. Component 2 will involve a mixed-method implementation evaluation to clarify how and why FDCC was implemented within the sites to inform future roll-out. Component 3 is a within-trial economic evaluation from a healthcare perspective to assess the cost-effectiveness of the Hubs relative to usual care and the implementation costs if Hubs were scaled and replicated. Ethics and dissemination Ethical approval was granted by the South Eastern Sydney Local Health District Human Research Ethics Committee in July 2021 (Project ID: 020/ETH03295). Results will be submitted for publication in peer-reviewed journals and presented at relevant conferences. Trial registration number ACTRN12621001088831

A Core Outcome Set for the Benefits and Adverse Events of Bariatric and Metabolic Surgery: The BARIACT Project.

This is the final version. Available from PLoS via the DOI in this record.BACKGROUND: Bariatric and metabolic surgery is used as a treatment for patients with severe and complex obesity. However, there is a need to improve outcome selection and reporting in bariatric surgery trials. A Core Outcome Set (COS), an agreed minimum set of outcomes reported in all studies of a specific condition, may achieve this. Here, we present the development of a COS for BARIAtric and metabolic surgery Clinical Trials-the BARIACT Study. METHODS AND FINDINGS: Outcomes identified from systematic reviews and patient interviews informed a questionnaire survey. Patients and health professionals were surveyed three times and asked to rate the importance of each item on a 1-9 scale. Delphi methods provided anonymised feedback to participants. Items not meeting predefined criteria were discarded between rounds. Remaining items were discussed at consensus meetings, held separately with patients and professionals, where the COS was agreed. Data sources identified 2,990 outcomes, which were used to develop a 130-item questionnaire. Round 1 response rates were moderate but subsequently improved to above 75% for other rounds. After rounds 2 and 3, 81 and 14 items were discarded, respectively, leaving 35 items for discussion at consensus meetings. The final COS included nine items: "weight," "diabetes status," "cardiovascular risk," "overall quality of life (QOL)," "mortality," "technical complications of the specific operation," "any re-operation/re-intervention," "dysphagia/regurgitation," and "micronutrient status." The main limitation of this study was that it was based in the United Kingdom only. CONCLUSIONS: The COS is recommended to be used as a minimum in all trials of bariatric and metabolic surgery. Adoption of the COS will improve data synthesis and the value of research data. Future work will establish methods for the measurement of the outcomes in the COS.Medical Research Council (MRC)National Institute for Health Research (NIHR)National Institute for Health Research (NIHR

Confocal energy-dispersive X-ray diffraction tomography employing a conical shell beam

We introduce a new high-energy X-ray diffraction tomography technique for volumetric materials characterization. In this method, a conical shell beam is raster scanned through the samples. A central aperture optically couples the diffracted flux from the samples onto a pixelated energy-resolving detector. Snapshot measurements taken during the scan enable the construction of depth-resolved dark-field section images. The calculation of d-spacing values enables the mapping of material phase in a volumetric image. We demonstrate our technique using five ~15 mm thick, axially separated samples placed within a polymer tray of the type used routinely in airport security stations. Our method has broad analytical utility due to scalability in both scan size and X-ray energy. Additional application areas include medical diagnostics, materials science, and process control