A care pathway approach to identifying factors that impact on diagnosis of heart disease in British Pakistani women

Purpose – The authors examined the cardiac care pathway with the aim of identifying factors that impact on diagnosis and treatment of coronary heart disease in British Pakistani women. Design/methodology/approach – This is an exploratory qualitative study. In depth interviews and focus groups with an opportunistic sample of Pakistani women and a purposive sample of clinicians working at different points along the care pathway were conducted. The authors used a pathways to care approach to illustrate how their individual and cumulative effect may contribute to differential receipt of treatment, including revascularisation, and health inequalities. Findings – Four major issues were identified: complex life circumstances; ‘‘atypical’’ presentation and ymptomatology; problems related to investigative testing; and poor communication. Mapping these barriers onto the Pathways to Care Model provided valuable insight into their impact on patients’progression through the different stages of the care pathway. Research limitations/implications – Adopting a care pathway approach demonstrated how individual factors have an impact at several points along the care pathway. It indicated where further, more detailed enquiry is merited and where intervention studies might usefully be directed to improve care. Practical implications – Examining the whole care pathway identified areas of service improvement that merit a co-ordinated response. Originality/value – The framework provided by the Pathways to Care Model offered insight into the causes of the previously observed attenuation in women’s progress along the cardiac diagnosis and treatment pathway and is an important first step to addressing this health inequality in a holistic way. Keywords Health, Gender, Inequalities, Women, Ethnicity, United Kingdom, Ethnic minorities, Personal health Paper type Research paper </p

Low cycle fatigue life prediction in shot-peened components of different geometries—part I: residual stress relaxation

In this study, the residual stress relaxation behaviour occurring during low-cycle fatigue in shot-peened specimens with either a flat or a notched geometry has been studied. A representative low-pressure steam turbine material, FV448, was used. The residual stress and strain hardening profiles caused by shot peening were measured experimentally and were then incorporated into a finite element model. By allowing for both effects of shot peening, the residual stress relaxation behaviour was successfully simulated using this model and correlated well with the experimental data. Although more modelling work may be required to simulate the interaction between shot peening effects and external loads in a range of notched geometries, the model predictions are consistent with the specimens tested in the current study. The novelty of this study lies in the development of such a modelling approach which can be used to effectively simulate the complex interaction between shot peening effects and external loads in notched regions. Compared with the un-notched geometry, the notched geometry was found to be more effective in retaining the improvement in fatigue life resulting from shot peening, by restricting the compressive residual stress relaxation during fatigue loading

Influence of oxidation on fatigue crack initiation and propagation in turbine disc alloy N18

Fatigue crack initiation and propagation behaviour in subsolvus heat treated turbine disc alloy N18 has been assessed in air and vacuum at 650 and 725oC under three-point loading. Fatigue crack initiation processes have been evaluated using single edge U-notch specimens under a 1-1-1-1 trapezoidal loading waveform along with interrupted tests at 650oC to allow intermittent observations of the notch surface. The results show apparent grain boundary (GB) oxidation can occur under an oxygen partial pressure of 10-2?10-3Pa. Cracks mainly initiate from grain boundaries or ?/?? interfaces due to the formation and subsequent cracking of Cr-rich and/or Co-rich oxides, and occasionally initiate from surface pores. Fatigue life in these tests appears to be dominated by this crack initiation process and is significantly reduced by increasing temperature and/or application of an oxidizing environment. Crack growth tests conducted under 1-1-1-1 and 1-20-1-1 loading waveforms indicate that oxidation significantly degrades the crack growth resistance of N18 and is associated with more intergranular fracture surface features. Additional oxidation effects on propagation caused by higher temperature or prolonging dwell time appear limited, whereas a prolonged dwell period seems to instead promote additional creep process, which further enhance crack growth, especially at higher temperature

The receptor protein tyrosine phosphatase PTPRB negatively regulates FGF2-dependent branching morphogenesis

PTPRB is a transmembrane protein tyrosine phosphatase known to regulate blood vessel remodelling and angiogenesis. Here we demonstrate that PTPRB negatively regulates branching morphogenesis in the mammary epithelium. We show that Ptprb is highly expressed in adult mammary stem cells and also, although at lower levels, in estrogen receptor positive luminal cells. During mammary development Ptprb expression is down-regulated during puberty, a period of extensive of ductal outgrowth and branching. In vivo shRNA knockdown of Ptprb in the cleared mammary fat pad transplant assay resulted in smaller epithelial outgrowths with an increased branching density and also increased branching in an in vitro organoid assay. Organoid branching was dependent on stimulation by FGF2, and Ptprb knockdown in mammary epithelial cells resulted in a higher level of FGFR activation and ERK1/2 phosphorylation, both at baseline and following FGF2 stimulation. Therefore, PTPRB regulates branching morphogenesis in the mammary epithelium by modulating the response of the FGFR signalling pathway to FGF stimulation. Considering the importance of branching morphogenesis in multiple taxa, our findings have general importance outside mammary developmental biology

International Journal of Fatigue, Volume 54:Evaluating surface deformation and near surface strain hardening resulting from shot peening a tempered martensitic steel and application to low cycle fatigue

The plastic deformation resulting from shot peening treatments applied to the ferritic heat resistant steelFV448 has been investigated. Two important effects have been quantified: surface roughness and strainhardening. 2D and 3D tactile and optical techniques for determining surface roughness amplitude parametershave been investigated; it was found that whilst Ra and Sa were consistent, Sz was generally higherthan Rz due to the increased probability of finding the worst case surface feature. Three different methodsfor evaluating the plastic strain profile have been evaluated with a view to establishing the variation inyield strength near the surface of a shot peened component. Microhardness, X-ray diffraction (XRD) linebroadening and electron backscatter diffraction (EBSD) local misorientation techniques were applied toboth uniaxially deformed calibration samples of known plastic strain and samples shot peened at intensitiesvarying from 4A to 18A to establish the variation in plastic strain and hence the variation in yieldstrength. The results from the three methods were compared; XRD and EBSD profiles were found to bethe most similar with microhardness profiles extending much deeper into the sample. Changes in themeasured plastic strain profile after exposure to low cycle fatigue and the correlation of these changeswith the cyclic stress–strain behaviour of the material are also discussed with a view to assessing theimportance of the dislocation profile in component life assessment procedures. 2013 Elsevier Ltd. All rights reserved

Slugging their way to immortality: Driving mammary epithelial cells into a stem cell-like state

Delineating the molecular factors that define and maintain the mammary stem cell state is vital for understanding normal development and tumourigenesis. A recent study by Guo and colleagues identifies two master transcriptional regulators of mammary stem cells, Slug and Sox9, ectopic expression of which confers stem cell attributes on differentiated mammary epithelial cells. Slug and Sox9 expression was also shown to determine in vivo metastatic potential of human breast cancer cell lines. Understanding these factors in the context of normal lineage differentiation is an important step toward elucidating the mammary epithelial cell hierarchy and the origins of cancer stem cells

Annexin A8 identifies a subpopulation of transiently quiescent c-kit positive luminal progenitor cells of the ductal mammary epithelium

We have previously shown that Annexin A8 (ANXA8) is strongly associated with the basal-like subgroup of breast cancers, including BRCA1-associated breast cancers, and poor prognosis; while in the mouse mammary gland AnxA8 mRNA is expressed in low-proliferative isolated pubertal mouse mammary ductal epithelium and after enforced involution, but not in isolated highly proliferative terminal end buds (TEB) or during pregnancy. To better understand ANXA8’s association with this breast cancer subgroup we established ANXA8’s cellular distribution in the mammary gland and ANXA8’s effect on cell proliferation. We show that ANXA8 expression in the mouse mammary gland was strong during pre-puberty before the expansion of the rudimentary ductal network and was limited to a distinct subpopulation of ductal luminal epithelial cells but was not detected in TEB or in alveoli during pregnancy. Similarly, during late involution its expression was found in the surviving ductal epithelium, but not in the apoptotic alveoli. Double-immunofluorescence (IF) showed that ANXA8 positive (+ve) cells were ER-alpha negative (−ve) and mostly quiescent, as defined by lack of Ki67 expression during puberty and mid-pregnancy, but not terminally differentiated with ~15% of ANXA8 +ve cells re-entering the cell cycle at the start of pregnancy (day 4.5). RT-PCR on RNA from FACS-sorted cells and double-IF showed that ANXA8+ve cells were a subpopulation of c-kit +ve luminal progenitor cells, which have recently been identified as the cells of origin of basal-like breast cancers. Over expression of ANXA8 in the mammary epithelial cell line Kim-2 led to a G0/G1 arrest and suppressed Ki67 expression, indicating cell cycle exit. Our data therefore identify ANXA8 as a potential mediator of quiescence in the normal mouse mammary ductal epithelium, while its expression in basal-like breast cancers may be linked to ANXA8’s association with their specific cells of origin