A Study to investigate the role of p27 and Cyclin E immunoexpression as a prognostic factor in early breast carcinoma

<p>Abstract</p> <p>Background</p> <p>Cyclin E and p27 expression is easy to assess in human tissues by standard immunohistochemical techniques. Immunohistochemistry is cost effective, relatively easy to perform and will play more of a role in the future management of cancer. The aim of this study was to investigate the role of p27 and cyclin E immunoexpression as a prognostic factor in early breast carcinoma.</p> <p>Methods</p> <p>Cyclin E and p27 immunohistochemistry was performed on sixty six cases of breast carcinoma submitted over a five year period to the Division of Anatomical Pathology, Groote Schuur hospital; Whittaker and Associates; and PathCare. All tumours included in this study were less than 5 cm in diameter (pT1 and pT2 stage) and all the patients had wide local excisions performed. Follow up information was obtained from patient folders in the Department of Radiation Oncology.</p> <p>Results</p> <p>There was no significant association of cyclin E and p27 expression with distant metastasis free survival (MFS) for all invasive carcinomas in contrast to grade, lymph node spread and vascular invasion. However, there was a statistically significant direct association of cyclin E with distant metastases in all invasive carcinomas, in the subgroup of infiltrating duct carcinomas (IDC) and in the node negative group when cyclin E was stratified as negative and positive (low/high). In this study of early breast carcinoma, only 9/66 cases showed cyclin E expression. Of these, four patients had distant metastases, one patient had a local recurrence and four patients were alive at last follow-up. Furthermore, cyclin E expression was significantly associated with grade, lymph node spread, oestrogen receptor status and histological type. None of the lobular carcinomas showed cyclin E positivity and only one case of lobular carcinoma presented with distant metastases.</p> <p>59/66 cases were positive (low/high) for p27 while seven cases were negative, 22 cases showed low expression and 37 cases demonstrated high p27 expression.</p> <p>p27 was significantly associated with oestrogen receptor status only for all invasive carcinomas and in the IDC group. There was no statistical relationship between p27 and cyclin E, but 50 (76%) tumours with positive p27 expression were negative for cyclin E. There were similar results for the invasive ductal carcinoma subgroup.</p> <p>Conclusion</p> <p>This study shows that p27 and cyclin E are not good independent prognostic markers for early breast carcinoma in contrast to grade, lymph node spread and vascular invasion for all invasive carcinomas. However, cyclin E provides some prognostic value as there is a direct statistical association with the development of distant metastases. Many previous studies have correlated overexpression of cyclin E with an aggressive course. The inverse relationship between p27 and cyclin E expression which has been reported in the literature has been highlighted, but this was not statistically significant. Most cases showed positive p27 expression and negative Cyclin E expression. This may be due to the early stage of the disease.</p

Adaptation and conservation insights from the koala genome

The koala, the only extant species of the marsupial family Phascolarctidae, is classified as ‘vulnerable’ due to habitat loss and widespread disease. We sequenced the koala genome, producing a complete and contiguous marsupial reference genome, including centromeres. We reveal that the koala’s ability to detoxify eucalypt foliage may be due to expansions within a cytochrome P450 gene family, and its ability to smell, taste and moderate ingestion of plant secondary metabolites may be due to expansions in the vomeronasal and taste receptors. We characterized novel lactation proteins that protect young in the pouch and annotated immune genes important for response to chlamydial disease. Historical demography showed a substantial population crash coincident with the decline of Australian megafauna, while contemporary populations had biogeographic boundaries and increased inbreeding in populations affected by historic translocations. We identified genetically diverse populations that require habitat corridors and instituting of translocation programs to aid the koala’s survival in the wild

West Antarctic ice loss influenced by internal climate variability and anthropogenic forcing

Recent ice loss from the West Antarctic Ice Sheet has been caused by ocean melting of ice shelves in the Amundsen Sea. Eastward wind anomalies at the shelf break enhance the import of warm Circumpolar Deep Water onto the Amundsen Sea continental shelf, which creates transient melting anomalies with an approximately decadal period. No anthropogenic influence on this process has been established. Here, we combine observations and climate model simulations to suggest that increased greenhouse gas forcing caused shelf-break winds to transition from mean easterlies in the 1920s to the near-zero mean zonal winds of the present day. Strong internal climate variability, primarily linked to the tropical Pacific, is superimposed on this forced trend. We infer that the Amundsen Sea experienced decadal ocean ariability throughout the twentieth century, with warm anomalies gradually becoming more prevalent, offering a credible explanation for the ongoing ice loss. Existing climate model projections show that strong future greenhouse gas forcing creates persistent mean westerly shelf-break winds by 2100, suggesting a further enhancement of warm ocean anomalies. These wind changes are weaker under a scenario in which greenhouse gas concentrations are stabilized

"This does my head in". Ethnographic study of self-management by people with diabetes

<p>Abstract</p> <p>Background</p> <p>Self-management is rarely studied 'in the wild'. We sought to produce a richer understanding of how people live with diabetes and why self-management is challenging for some.</p> <p>Method</p> <p>Ethnographic study supplemented with background documents on social context. We studied a socio-economically and ethnically diverse UK population. We sampled 30 people with diabetes (15 type 1, 15 type 2) by snowballing from patient groups, community contacts and NHS clinics. Participants (aged 5-88, from a range of ethnic and socio-economic groups) were shadowed at home and in the community for 2-4 periods of several hours (total 88 visits, 230 hours); interviewed (sometimes with a family member or carer) about their self-management efforts and support needs; and taken out for a meal. Detailed field notes were made and annotated. Data analysis was informed by structuration theory, which assumes that individuals' actions and choices depend on their dispositions and capabilities, which in turn are shaped and constrained (though not entirely determined) by wider social structures.</p> <p>Results</p> <p>Self-management comprised both practical and cognitive tasks (e.g. self-monitoring, menu planning, medication adjustment) and socio-emotional ones (e.g. coping with illness, managing relatives' input, negotiating access to services or resources). Self-management was hard work, and was enabled or constrained by economic, material and socio-cultural conditions within the family, workplace and community. Some people managed their diabetes skilfully and flexibly, drawing on personal capabilities, family and social networks and the healthcare system. For others, capacity to self-manage (including overcoming economic and socio-cultural constraints) was limited by co-morbidity, cognitive ability, psychological factors (e.g. under-confidence, denial) and social capital. The consequences of self-management efforts strongly influenced people's capacity and motivation to continue them.</p> <p>Conclusion</p> <p>Self-management of diabetes is physically, intellectually, emotionally and socially demanding. Non-engagement with self-management may make sense in the context of low personal resources (e.g. health literacy, resilience) and overwhelming personal, family and social circumstances. Success of self-management as a policy solution will be affected by interacting influences at three levels: [a] at micro level by individuals' dispositions and capabilities; [b] at meso level by roles, relationships and material conditions within the family and in the workplace, school and healthcare organisation; and [c] at macro level by prevailing economic conditions, cultural norms and expectations, and the underpinning logic of the healthcare system. We propose that the research agenda on living with diabetes be extended and the political economy of self-management systematically studied.</p

An evaluation of gender equity in different models of primary care practices in Ontario

Background: The World Health Organization calls for more work evaluating the effect of health care reforms on gender equity in developed countries. We performed this evaluation in Ontario, Canada where primary care models resulting from reforms co-exist. // Methods: This cross sectional study of primary care practices uses data collected in 2005-2006. Healthcare service models included in the study consist of fee for service (FFS) based, salaried, and capitation based. We compared the quality of care delivered to women and men in practices of each model. We performed multi-level, multivariate regressions adjusting for patient socio-demographic and economic factors to evaluate vertical equity, and adjusting for these and health factors in evaluating horizontal equity. We measured seven dimensions of health service delivery (e.g. accessibility and continuity) and three dimensions of quality of care using patient surveys (n = 5,361) and chart abstractions (n = 4,108). // Results: Health service delivery measures were comparable in women and men, with differences ≤ 2.2% in all seven dimensions and in all models. Significant gender differences in the health promotion subjects addressed were observed. Female specific preventive manoeuvres were more likely to be performed than other preventive care. Men attending FFS practices were more likely to receive influenza immunization than women (Adjusted odds ratio: 1.75, 95% confidence intervals (CI) 1.05, 2.92). There was no difference in the other three prevention indicators. FFS practices were also more likely to provide recommended care for chronic diseases to men than women (Adjusted difference of -11.2%, CI -21.7, -0.8). A similar trend was observed in Community Health Centers (CHC). // Conclusions: The observed differences in the type of health promotion subjects discussed are likely an appropriate response to the differential healthcare needs between genders. Chronic disease care is non equitable in FFS but not in capitation based models. We recommend that efforts to monitor and address gender based differences in the delivery of chronic disease management in primary care be pursued.Funding for the original study on which this research is based was provided by the Ontario Ministry of Health and Long Term Care Primary Health Care Transition Fund. The views expressed in this report are the views of the authors and do not necessarily reflect those of the Ontario Ministry of Health and Long Term Care

Greenland ice sheet surface mass loss: recent developments in observation and modeling

Surface processes currently dominate Greenland ice sheet (GrIS) mass loss. We review recent developments in the observation and modelling of GrIS surface mass balance (SMB), published after the July 2012 deadline for the Fifth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC AR5). Since IPCC AR5 our understanding of GrIS SMB has further improved, but new observational and model studies have also revealed that temporal and spatial variability of many processes are still poorly quantified and understood, e.g. bio-albedo, the formation of ice lenses and their impact on lateral meltwater transport, heterogeneous vertical meltwater transport (‘piping’), the impact of atmospheric circulation changes and mixed-phase clouds on the surface energy balance and the magnitude of turbulent heat exchange over rough ice surfaces. As a result, these processes are only schematically or not at all included in models that are currently used to assess and predict future GrIS surface mass loss

Measuring proliferation in breast cancer: practicalities and applications

Various methods are available for the measurement of proliferation rates in tumours, including mitotic counts, estimation of the fraction of cells in S-phase of the cell cycle and immunohistochemistry of proliferation-associated antigens. The evidence, advantages and disadvantages for each of these methods along with other novel approaches is reviewed in relation to breast cancer. The potential clinical applications of proliferative indices are discussed, including their use as prognostic indicators and predictors of response to systemic therapy

Self-management education for adults with poorly controlled epilepsy (SMILE (UK)): statistical, economic and qualitative analysis plan for a randomised controlled trial

BACKGROUND: There is a need to test the effectiveness of new educational interventions for people with poorly controlled epilepsy. The SMILE (self-management education for adults with poorly controlled epilepsy) trial evaluates a complex service intervention that involves a 2-day self-management course with the aim of improving quality of life and clinical outcomes. This article describes the statistical, economic, and qualitative analysis plan for the trial. METHODS AND DESIGN: SMILE is a pragmatic, parallel design, two-arm, multi-centre randomised controlled superiority trial of a group-based interactive course compared with treatment as usual for people who have experienced two or more seizures in the past 12 months. RESULTS: A summary of the objectives and design of the trial are reported as well as the manner in which the data will be summarised and inferentially analysed. This includes the type of modelling that will be employed for each of the primary and secondary outcomes and the methods by which the assumptions of these models will be checked. Strategies are described for handling clustering of outcome data, missing observations, and treatment non-compliance. CONCLUSION: This update to the previously published trial protocol provides a description of the trial analysis which is transparent and specified before any outcome data are available. It also provides guidance to those planning the analysis of similar trials. TRIAL REGISTRATION: Current Controlled Trials ISRCTN57937389; date assigned: 27 March 2013

Key signaling nodes in mammary gland development and cancer: β-catenin

β-Catenin plays important roles in mammary development and tumorigenesis through its functions in cell adhesion, signal transduction and regulation of cell-context-specific gene expression. Studies in mice have highlighted the critical role of β-catenin signaling for stem cell biology at multiple stages of mammary development. Deregulated β-catenin signaling disturbs stem and progenitor cell dynamics and induces mammary tumors in mice. Recent data showing deregulated β-catenin signaling in metaplastic and basal-type tumors suggest a similar link to reactivated developmental pathways and human breast cancer. The present review will discuss β-catenin as a central transducer of numerous signaling pathways and its role in mammary development and breast cancer