Oestrogen receptor dynamics and cell signalling

Oestrogen receptors (ER) have classically been described as ligand-inducible nuclear transcription factors. The pleiotrophic effects of ER function have a predominant role in the direct regulation of the growth, differentiation and development of tissues of the human reproductive system. There are two ER subtypes, ER and ER which differ in their specificity for ligand and the consequent actions they orchestrate. Moreover, the latter exists in multiple splice variants of which ER is the only fully functional homologue. Research into the underlying differences in subtype responses to ligand has involved examination of the intranuclear dynamics of individual receptor subtypes. Studies into the mobility of ER in response to ligand have exclusively focused on studies of full length ER and ER independently in transfected cell lines. The studies described in this thesis have investigated the kinetics of ER using Fluorescence Recovery After Photobleaching (FRAP) in infected cell lines which lends itself to more precise expression of the subtype of interest. The morphological impact of natural oestrogenic and synthetic ligands on ERs was examined and the influence on the intranuclear dynamics assessed. Further to this, the effect of co-expression of different ER subtype combinations was examined. Studies on the intranuclear mobility of ER have confirmed and extended the findings of others. Previous work on the development of ER agonists and antagonists has been to target specific overexpressing ER subtypes in a physiological setting. In this study, we demonstrated for the first time an overwhelming ER -selective effect in slowing the rate of mobility within the nucleus, suggesting the study of intranuclear dynamics is an important parameter for the examination of efficacy of a compound. Differential responses to ligand based on co-infected partnerships indicate that heterodimerisation has a profound effect in augmenting ligand-dependent regulation and activity

Literacy-Rich Emotional Intelligence Curriculum Guide

This research originated from my experience teaching in a school designed as an alternative to expulsion for a large public school district. The premise was that students could return to their traditional school setting after the appropriate “time-out” had been completed. My research and experience speaks to the fact that the threat of expulsion and required compliance of strict behavior codes rarely changed student behavior and did not make at-risk adolescents better students. I found that students who met the criteria for an expulsion referral came from all walks of life, had a variety of learning styles, and covered the full spectrum of academic ability. Almost without exception however, these students did share some specific commonalities. These students all had behavior problems and nearly every student reported they struggled with handling their anger and reading their school work. My research and classroom experience lead me to focus on teaching emotional intelligence skills while simultaneously building in differentiated lessons to address academic skills, in order to help at-risk students be more success in their personal and academic lives. In this project I used the book, Power Source: Taking Charge of Your Life (Casarjian & Casarjian, 2003), as a framework to build a Literacy-Rich Emotional Intelligence Curriculum Guide. My students loved this book, so I used it as the main text of the curriculum. I have enriched the Power Source modules with lessons that teach and reinforce the vocabulary of the Power Source book. I have recommended reading strategies for each topic and have provided a reading list of various reading levels and interests that coordinate with four Power Source modules of self-discovery and meditation, risk-taking, choosing friends, and family relationships. I have also included the internet link to the School-Wide Enrichment Model (Reis, et. al, 2005) down-loadable Bookmarks, which enable rich discussions during mini-conferences between teachers and students

Engaging the disengaged indefinitely, and with no budget: creating a sustainable model for student library ambassadors

University Libraries offer a wide range of services and facilities to help enhance the student learning experience and to aid the transition into learning at University. Often, too few Science and Engineering students fully engage with the services and facilities on offer and therefore do not benefit from the opportunities available to them. Drawing on research highlighting the value of peer support, and the fact that students are far more likely to use their peers as an information source than ‘experts’, Loughborough University Library obtained small project funding in 2010 to employ four Student Ambassadors in a pilot project to improve student engagement with the Library. The successful project demonstrated the potency of the idea in engaging with students, particularly non-users, a large proportion of which are based in the Science and Engineering Faculties. In the absence of continued funding, the challenge, addressed here, is how to make such posts sustainable. Past experience at both Nottingham and Loughborough Universities has proven how difficult it is to recruit students on a voluntary basis to engage with University Libraries. In this paper, an innovative and creative method of recruiting and supporting “Learning Resource Leaders” (LRLs) at Nottingham and Loughborough Universities is discussed. The strategies employed have resulted in the recruitment of four LRLs – two at each institution – supported by an industrial sponsor who provides a package of non-monetary incentives. The paper also describes the techniques used by the LRLs to disseminate information about the resources offered by the University Libraries and to engage with the student cohort

Development and validation of a novel risk prediction algorithm to estimate 10-year risk of oesophageal cancer in primary care: prospective cohort study and evaluation of performance against two other risk prediction models

BackgroundMethods to identify patients at increased risk of oesophageal cancer are needed to better identify those for targeted screening. We aimed to derive and validate novel risk prediction algorithms (CanPredict) to estimate the 10-year risk of oesophageal cancer and evaluate performance against two other risk prediction models.MethodsProspective open cohort study using routinely collected data from 1804 QResearch® general practices. We used 1354 practices (12.9 M patients) to develop the algorithm. We validated the algorithm in 450 separate practices from QResearch (4.12 M patients) and 355 Clinical Practice Research Datalink (CPRD) practices (2.53 M patients). The primary outcome was an incident diagnosis of oesophageal cancer found in GP, mortality, hospital, or cancer registry data. Patients were aged 25–84 years and free of oesophageal cancer at baseline. Cox proportional hazards models were used with prediction selection to derive risk equations. Risk factors included age, ethnicity, Townsend deprivation score, body mass index (BMI), smoking, alcohol, family history, relevant co-morbidities and medications. Measures of calibration, discrimination, sensitivity, and specificity were calculated in the validation cohorts.FindingThere were 16,384 incident cases of oesophageal cancer in the derivation cohort (0.13% of 12.9 M). The predictors in the final algorithms were: age, BMI, Townsend deprivation score, smoking, alcohol, ethnicity, Barrett's oesophagus, hiatus hernia, H. pylori infection, use of proton pump inhibitors, anaemia, lung and blood cancer (with breast cancer in women). In the QResearch validation cohort in women the explained variation (R2) was 57.1%; Royston’s D statistic 2.36 (95% CI 2.26–2.46); C statistic 0.859 (95% CI 0.849–0.868) and calibration was good. Results were similar in men. For the 20% at highest predicted risk, the sensitivity was 76%, specificity was 80.1% and the observed risk at 10 years was 0.76%. The results from the CPRD validation were similar.InterpretationWe have developed and validated a novel prediction algorithm to quantify the absolute risk of oesophageal cancer. The CanPredict algorithms could be used to identify high risk patients for targeted screening

Economic (gross cost) analysis of systematically implementing a programme of advance care planning in three Irish nursing homes.

Background: Although advance care planning (ACP) and the use of advanced care directives (ACD) and end-of-life care plans are associated with a reduction in inappropriate hospitalisation, there is little evidence supporting the economic benefits of such programmes. We assessed the economic impact (gross savings) of the Let Me Decide (LMD) ACP programme in Ireland, specifically the impact on hospitalisations, bed days and location of resident deaths, before and after systematic implementation of the LMD-ACP combined with a palliative care education programme. Methods: The LMD-ACP was introduced into three long-term care (LTC) facilities in Southern Ireland and outcomes were compared pre and post implementation. In addition, 90 staff were trained in a palliative care educational programme. Economic analysis including probabilistic sensitivity analysis was performed. Results: The uptake of an ACD or end-of-life care post-implementation rose from 25 to 76 %. Post implementation, there were statistically significant decreases in hospitalisation rates from baseline (hospitalisation incidents declined from 27.8 to 14.6 %, z = 3.96, p < 0.001; inpatient hospital days reduced from 0.54 to 0.36 %, z = 8.85, p < 0.001). The percentage of hospital deaths also decreased from 22.9 to 8.4 %, z = 3.22, p = 0.001. However, length of stay (LOS) increased marginally (7–9 days). Economic analysis suggested a cost-reduction related to reduced hospitalisations ranging between €10 and €17.8 million/annum and reduction in ambulance transfers, estimated at €0.4 million/annum if these results were extrapolated nationally. When unit costs and LOS estimates were varied in scenario analyses, the expected cost reduction owing to reduced hospitalisations, ranged from €17.7 to €42.4 million nationally. Conclusions: Implementation of the LMD-ACP (ACD/end-of-life care plans combined with palliative care education) programme resulted in reduced rates of hospitalisation. Despite an increase in LOS, likely reflecting more complex care needs of admitted residents, gross costs were reduced and scenario analysis projected large annual savings if these results were extrapolated to the wider LTC population in Ireland

The inter-rater reliability of the Risk Instrument for Screening in the Community

Predicting risk of adverse healthcare outcomes is important to enable targeted delivery of interventions. The Risk Instrument for Screening in the Community (RISC), designed for use by public health nurses (PHNs), measures the one-year risk of hospitalisation, institutionalisation and death in community-dwelling older adults according to a five-point global risk score: from low (score 1,2), medium (3) and high (4,5). We examined the inter-rater reliability (IRR) of the RISC between student PHNs (n=32) and expert raters using six cases (two low, medium and high-risk), scored before and after RISC training. Correlations increased for each adverse outcome, statistically significantly for institutionalisation (r=0.72 to 0.80,p=0.04) and hospitalisation, (r=0.51 to 0.71,p<0.01) but not death. Training improved accuracy for low-risk but not all high-risk cases. Overall, the RISC showed good IRR, which increased after RISC training. That reliability reduced for some high-risk cases suggests that the training programme requires adjustment to further improve IRR

The Ursinus Weekly, April 27, 1972

Ursinus suffers blackout; Transformer explodes • Dr. Helen T. Garrett dies • UC students experience teaching • Dr. Robert M. Veatch to speak at Ursinus College forum • Dr. Allan Lake Rice speaks at conference • Students inducted into Omicron Delta Epsilon • Ursinus seeks $200,000 gift • Lantern elects officers for \u2772-\u2773; Spring issue expected in late May • Editorial: Stop the war • Focus: Jane Siegel • Strike • Faculty portrait: Dr. Gayle Byerly • Guest column: Dr. Allan Rice on war and peace • Letters to the editor: The need of a psychologist; Open letter to security • W.C. rains on our parade • Sing sets record • Bartholomew wins two • Ursinus starts baseball season • Travelin\u27 5\u27s history told • Modern Dance Club: fun for allhttps://digitalcommons.ursinus.edu/weekly/1123/thumbnail.jp