Finding a way: long-term care homes to support dementia

An ageing demographic has increased the number of people with dementia. Although dementia is commonly associated with memory loss, other early symptoms include difficulty with wayfinding. Dementia alters visuo-spatial perception and the processes used to interpret the physical environment. The role of the design of the physical environment for people with dementia has gained increased recognition. Despite this, design for dementia is often overlooked, focusing on issues relating to physical impairment. This paper presents the results of a PhD study and aims to examine the role of the design of the physical environment in supporting wayfinding for people with dementia living in long-term care settings in Northern Ireland. Mixed methods combined the observation of wayfinding walks and conversational style interviews to elicit perspectives and experiences of residents with dementia. The findings aim to promote well-being for those with dementia living in long-term care settings

Faculty and Student Perspectives on Open Education at Gettysburg College

Commercially available textbooks and course materials are often expensive for students and sometimes don’t cover topics in exactly the way you might prefer to teach. Freely available and completely adaptable open educational resources (OER) have risen in popularity in recent years, both nationwide and locally, as a way to address both issues. Join us to hear from Alice Brawley Newlin (Management), Tasha Gownaris (Environmental Studies), Chris Oechler (Spanish), and Ryan Nedrow ’22 to hear about their experiences with OER in the classroom. Panelists will talk honestly about the benefits, drawbacks, challenges, and successes associated with open course materials in order to give you a better sense of whether OER might be a good fit in your own context

Complete Break Up of Ortho Positronium (Ps)- Hydrogenic ion System

The dynamics of the complete breakup process in an Ortho Ps - He+ system including electron loss to the continuum (ELC) is studied where both the projectile and the target get ionized. The process is essentially a four body problem and the present model takes account of the two centre effect on the electron ejected from the Ps atom which is crucial for a proper description of the ELC phenomena. The calculations are performed in the framework of Coulomb Distorted Eikonal Approximation. The exchange effect between the target and the projectile electron is taken into account in a consistent manner. The proper asymptotic 3-body boundary condition for this ionization process is also satisfied in the present model. A distinct broad ELC peak is noted in the fully differential cross sections (5DCS) for the Ps electron corroborating qualitatively the experiment for the Ps - He system. Both the dynamics of the ELC from the Ps and the ejected electron from the target He+ in the FDCS are studied using coplanar geometry. Interesting features are noted in the FDCS for both the electrons belonging to the target and the projectile.Comment: 14 pages,7 figure

Addition of abiraterone to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Model to estimate long-term survival, quality-adjusted survival, and cost-effectiveness

Background: Results from randomised trials show adding abiraterone acetate plus prednisolone (AAP) to standard of care (SOC) improves disease-free and overall survival in men with prostate cancer (PC) starting long-term hormone therapy for first time. Formal assessment is required of whether funding AAP here shows appropriate use of resources. This cost-effectiveness decision model tests if giving AAP to these patients is cost-effective using costs from English National Health Service, the largest nation where STAMPEDE recruited. / Methods: Health outcomes and costs were modelled using patient data from AAP comparison of STAMPEDE (recruitment 2011-14). This included 1917 men with high-risk, locally advanced metastatic or recurrent PC starting 1st-line hormone therapy. SOC was hormone therapy for ≥2 years with radiotherapy in pre-selected patients. If allocated to research group, AAP (AA 1000mg/day, P 5mg/day) was added to SOC. The model makes lifetime predictions of survival, costs and quality-adjusted lifeyears (QALYs), with costs and QALYs discounted at 3.5% annually. Sensitivity analyses were performed. / Results: The model predicted AAP would extend survival (discounted quality-adjusted survival) by 2.68y (1.46 QALYs) for metastatic patients and 0.30y (0.29 QALYs) for non-metastatic. The cost of AAP means it is not currently cost-effective in this setting, including with Patient Access Scheme costs for AAP and enzalutamide and similar reductions for cabazitaxel and Ra. If AAP’s price reduces after patent expiry as expected (90% reduction on BNF cost), it would be cost-effective in both patient groups, with incremental cost-effectiveness ratios below £10,000 (US$12,665) per QALY. AAP could also dominate in non-metastatic patients (i.e. lower costs and higher QALYs than SOC alone). / Conclusions: AAP could be cost-effective for patients with non-metastatic and metastatic disease with expected future pricing and may be cost-saving in the former. Policymakers should encourage license submissions and generic price reductions to facilitate use of AAP given cost-saving potential in addition to improving survival. / Clinical trial information: NCT00268476

Accumulation of copy number alterations and clinical progression across advanced prostate cancer.

BACKGROUND: Genomic copy number alterations commonly occur in prostate cancer and are one measure of genomic instability. The clinical implication of copy number change in advanced prostate cancer, which defines a wide spectrum of disease from high-risk localised to metastatic, is unknown. METHODS: We performed copy number profiling on 688 tumour regions from 300 patients, who presented with advanced prostate cancer prior to the start of long-term androgen deprivation therapy (ADT), in the control arm of the prospective randomised STAMPEDE trial. Patients were categorised into metastatic states as follows; high-risk non-metastatic with or without local lymph node involvement, or metastatic low/high volume. We followed up patients for a median of 7 years. Univariable and multivariable Cox survival models were fitted to estimate the association between the burden of copy number alteration as a continuous variable and the hazard of death or disease progression. RESULTS: The burden of copy number alterations positively associated with radiologically evident distant metastases at diagnosis (P=0.00006) and showed a non-linear relationship with clinical outcome on univariable and multivariable analysis, characterised by a sharp increase in the relative risk of progression (P=0.003) and death (P=0.045) for each unit increase, stabilising into more modest increases with higher copy number burdens. This association between copy number burden and outcome was similar in each metastatic state. Copy number loss occurred significantly more frequently than gain at the lowest copy number burden quartile (q=4.1 × 10-6). Loss of segments in chromosome 5q21-22 and gains at 8q21-24, respectively including CHD1 and cMYC occurred more frequently in cases with higher copy number alteration (for either region: Kolmogorov-Smirnov distance, 0.5; adjusted P<0.0001). Copy number alterations showed variability across tumour regions in the same prostate. This variance associated with increased risk of distant metastases (Kruskal-Wallis test P=0.037). CONCLUSIONS: Copy number alteration in advanced prostate cancer associates with increased risk of metastases at diagnosis. Accumulation of a limited number of copy number alterations associates with most of the increased risk of disease progression and death. The increased likelihood of involvement of specific segments in high copy number alteration burden cancers may suggest an order underlying the accumulation of copy number changes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00268476 , registered on December 22, 2005. EudraCT  2004-000193-31 , registered on October 4, 2004

Better Together: Expanding Rural Partnerships to Support Families

Chronic shortages of health, social service, and mental health professionals in rural areas necessitate creative partnerships in support of families. Cooperative extension professionals in Family and Consumer Sciences and community health nurses are introduced as trusted professionals in rural communities who can bring critical skills to human services teams. Multidisciplinary prevention programs offer particularly good contexts for county extension educators and community health nurses to work in collaboration with social workers. The case of grandparents raising grandchildren illustrates the critical roles that can be filled by professionals in these two fields to extend the reach of family support programs

Centrosome misorientation reduces stem cell division during ageing

Asymmetric division of adult stem cells generates one self- renewing stem cell and one differentiating cell, thereby maintaining tissue homeostasis. A decline in stem cell function has been proposed to contribute to tissue ageing, although the underlying mechanism is poorly understood. Here we show that changes in the stem cell orientation with respect to the niche during ageing contribute to the decline in spermatogenesis in the male germ line of Drosophila. Throughout the cell cycle, centrosomes in germline stem cells ( GSCs) are oriented within their niche and this ensures asymmetric division. We found that GSCs containing misoriented centrosomes accumulate with age and that these GSCs are arrested or delayed in the cell cycle. The cell cycle arrest is transient, and GSCs appear to re- enter the cell cycle on correction of centrosome orientation. On the basis of these findings, we propose that cell cycle arrest associated with centrosome misorientation functions as a mechanism to ensure asymmetric stem cell division, and that the inability of stem cells to maintain correct orientation during ageing contributes to the decline in spermatogenesis. We also show that some of the misoriented GSCs probably originate from dedifferentiation of spermatogonia.University of Michigan ; March of Dimes Basil O'Conner Starter Scholar Research Award ; Searle Scholar Program ; NIH [P01 DK53074, R01GM072006]We thank C. Gonzalez, D. McKearin, N. Rusan, M. Peifer and the Bloomington Stock Center for fly stocks; R. Lehmann, C. Field and the Developmental Studies Hybridoma Bank for antibodies; M. Kiel and D. Nakada for help with X-ray irradiation; and S. Morrison and T. Mahowald for comments on the manuscript. This research was supported by a University of Michigan start-up fund, March of Dimes Basil O'Conner Starter Scholar Research Award and the Searle Scholar Program (to Y.M.Y.), and NIH grants P01 DK53074 (to M.T.F.) and R01GM072006 (to A.J.H.).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62879/1/nature07386.pd

Ecological genetics in the North Atlantic: environmental gradients and adaptation at specific loci

The North Atlantic intertidal community provides a rich set of organismal and environmental material for the study of ecological genetics. Clearly defined environmental gradients exist at multiple spatial scales: there are broad latitudinal trends in temperature, meso-scale changes in salinity along estuaries, and smaller scale gradients in desiccation and temperature spanning the intertidal range. The geology and geography of the American and European coasts provide natural replication of these gradients, allowing for population genetic analyses of parallel adaptation to environmental stress and heterogeneity. Statistical methods have been developed that provide genomic neutrality tests of population differentiation and aid in the process of candidate gene identification. In this paper, we review studies of marine organisms that illustrate associations between an environmental gradient and specific genetic markers. Such highly differentiated markers become candidate genes for adaptation to the environmental factors in question, but the functional significance of genetic variants must be comprehensively evaluated. We present a set of predictions about locus-specific selection across latitudinal, estuarine, and intertidal gradients that are likely to exist in the North Atlantic. We further present new data and analyses that support and contradict these simple selection models. Some taxa show pronounced clinal variation at certain loci against a background of mild clinal variation at many loci. These cases illustrate the procedures necessary for distinguishing selection driven by internal genomic vs. external environmental factors. We suggest that the North Atlantic intertidal community provides a model system for identifying genes that matter in ecology due to the clarity of the environmental stresses and an extensive experimental literature on ecological function. While these organisms are typically poor genetic and genomic models, advances in comparative genomics have provided access to molecular tools that can now be applied to taxa with well-defined ecologies. As many of the organisms we discuss have tight physiological limits driven by climatic factors, this synthesis of molecular population genetics with marine ecology could provide a sensitive means of assessing evolutionary responses to climate change

Disabling knee pain – another consequence of obesity: Results from a prospective cohort study

BACKGROUND: Obesity is linked to knee osteoarthritis (OA) and knee pain. These are disabling problems that are more prevalent in older adults. No prospective study has estimated the impact of excess weight avoidance on the occurrence of knee pain in the general older population. The aim of this study was to investigate the influence of overweight and obesity on the onset and progression of knee pain and disability in older adults living in the community. METHODS: A prospective cohort study of people aged 50 and over registered with three general practices in North Staffordshire, UK. 5784 people who had responded to a survey in March 2000 were mailed a follow-up questionnaire in March 2003. The main outcome measures were self-reported knee pain and severe knee pain and disability at 3 years measured by the Western Ontario and McMaster Universities Osteoarthritis index. RESULTS: Adjusted response to follow-up was 75%. Among responders with no knee pain at baseline, obesity predicted onset of severe knee pain (relative risk 2.8; 95% CI 1.8, 4.5 compared to normal body mass index (BMI) category). Considering overweight and obese categories together, 19% of new cases of severe knee pain over a 3-year period could potentially be avoided by a one-category shift downwards in BMI; this includes almost half of the new cases that arose in the obese group. CONCLUSION: Obesity accounts for a substantial proportion of severe disabling knee pain. As knee pain is a common disabling condition in older adults living in the community, effective public health interventions about avoidance of excess weight could have a major impact on future lower limb disability in older adults

Prevention and early detection of prostate cancer

This Review was sponsored and funded by the International Society of Cancer Prevention (ISCaP), the European Association of Urology (EAU), the National Cancer Institute, USA (NCI) (grant number 1R13CA171707-01), Prostate Cancer UK, Cancer Research UK (CRUK) (grant number C569/A16477), and the Association for International Cancer Research (AICR