Mechanical suppression of osteolytic bone metastases in advanced breast cancer patients: A randomised controlled study protocol evaluating safety, feasibility and preliminary efficacy of exercise as a targeted medicine

Background: Skeletal metastases present a major challenge for clinicians, representing an advanced and typically incurable stage of cancer. Bone is also the most common location for metastatic breast carcinoma, with skeletal lesions identified in over 80% of patients with advanced breast cancer. Preclinical models have demonstrated the ability of mechanical stimulation to suppress tumour formation and promote skeletal preservation at bone sites with osteolytic lesions, generating modulatory interference of tumour-driven bone remodelling. Preclinical studies have also demonstrated anti-cancer effects through exercise by minimising tumour hypoxia, normalising tumour vasculature and increasing tumoural blood perfusion. This study proposes to explore the promising role of targeted exercise to suppress tumour growth while concomitantly delivering broader health benefits in patients with advanced breast cancer with osteolytic bone metastases. Methods: This single-blinded, two-armed, randomised and controlled pilot study aims to establish the safety, feasibility and efficacy of an individually tailored, modular multi-modal exercise programme incorporating spinal isometric training (targeted muscle contraction) in 40 women with advanced breast cancer and stable osteolytic spinal metastases. Participants will be randomly assigned to exercise or usual medical care. The intervention arm will receive a 3-month clinically supervised exercise programme, which if proven to be safe and efficacious will be offered to the control-arm patients following study completion. Primary endpoints (programme feasibility, safety, tolerance and adherence) and secondary endpoints (tumour morphology, serum tumour biomarkers, bone metabolism, inflammation, anthropometry, body composition, bone pain, physical function and patient-reported outcomes) will be measured at baseline and following the intervention. Discussion: Exercise medicine may positively alter tumour biology through numerous mechanical and nonmechanical mechanisms. This randomised controlled pilot trial will explore the preliminary effects of targeted exercise on tumour morphology and circulating metastatic tumour biomarkers using an osteolytic skeletal metastases model in patients with breast cancer. The study is principally aimed at establishing feasibility and safety. If proven to be safe and feasible, results from this study could have important implications for the delivery of this exercise programme to patients with advanced cancer and sclerotic skeletal metastases or with skeletal lesions present in haematological cancers (such as osteolytic lesions in multiple myeloma), for which future research is recommended. Trial registration: anzctr.org.au, ACTRN-12616001368426. Registered on 4 October 2016

New technologies of representation, collaborative autoethnographies and ‘taking it public’: An example from ‘Facilitating Communication on Sexual Topics in Education’

New technologies for representing and communicating autoethnographies make it possible to be publically visible in new and interesting ways that weren’t possible prior to the digital revolution. An important ingredient in this process is the internet platforms that can make the digitisation of performances accessible across the world, even for short, modest creations from less experienced digital storytellers and film makers. As an illustration of the potential applications of digital technologies for ‘taking’ autoethnographic research to the ‘public,’ and making our research accessible to a wider audience we share ‘Reverberations,’ a collaborative autoethnography exploring bullying, homophobia, and other types of sexual harassment and associated feelings of shame, embarrassment and fear which often surround these topics

The international phase 4 validation study of the EORTC QLQ-SWB32: a stand-alone measure of spiritual wellbeing (SWB) for people receiving palliative care for cancer

The EORTC Quality of Life (QL) Group has just completed the final phase (field-testing and validation) of an international project to develop a stand-alone measure of spiritual wellbeing (SWB) for palliative cancer patients. Participants (n= 451) - from 14 countries on four continents; 54% female; 188 Christian, 50 Muslim, 156 with no religion - completed a provisional 36-item measure of SWB plus the EORTC QLQ-C15-PAL (PAL), then took part in a structured debriefing interview. All items showed good score distribution across response categories. We assessed scale structure using Principal Component Analysis and Rasch analysis, and explored construct validity, and convergent/divergent validity with the PAL. Twenty-two items in four scoring scales (Relationship with Self, Relationships with Others, Relationship with Something Greater, and Existential) explained 53% of the variance. The measure also includes a global SWB item and nine other items. Scores on the PAL global QL item and Emotional Functioning scale weakly-moderately correlated with scores on the global SWB item and two of the four SWB scales. This new validated 32-item SWB measure addresses a distinct aspect of QL, and is now available for use in research and clinical practice, with a role as both a measurement and an intervention tool

Recent Results from Epitaxial Growth on Step Free 4H-SiC Mesas

This paper updates recent progress made in growth, characterization, and understanding of high quality homoepitaxial and heteroepitaxial films grown on step-free 4H-SiC mesas. First, we report initial achievement of step-free 4H-SiC surfaces with carbon-face surface polarity. Next, we will describe further observations of how step-free 4H-SiC thin lateral cantilever evolution is significantly impacted by crystal faceting behavior that imposes non-uniform film thickness on cantilever undersides. Finally, recent investigations of in-plane lattice constant mismatch strain relief mechanisms observed for heteroepitaxial growth of 3C-SiC as well as 2H-AlN/GaN heterofilms on step-free 4H-SiC mesas will be reviewed. In both cases, the complete elimination of atomic heterointerface steps on the mesa structure enables uniquely well-ordered misfit dislocation arrays to form near the heterointerfaces with remarkable lack of dislocations threading vertically into the heteroepilayers. In the case of 3C-SiC heterofilms, it has been proposed that dislocation half-loops nucleate at mesa edges and glide laterally along the step-free 3C/4H interfaces. In contrast, 3C-SiC and 2H-AlN/GaN heterofilms grown on 4H-SiC mesas with steps exhibit highly disordered interface misfit dislocation structure coupled with 100X greater density of dislocations threading through the thickness of the heteroepilayers. These results indicate that the presence of steps at the heteroepitaxial interface (i.e., on the initial heteroepitaxial nucleation surface) plays a highly important role in the defect structure, quality, and relaxation mechanisms of single-crystal heteroepitaxial films

Are Patient Self-Reported Outcome Measures Sensitive Enough to Be Used as End Points in Clinical Trials?: Evidence from the United Kingdom Glaucoma Treatment Study

Purpose The United Kingdom Glaucoma Treatment Study (UKGTS) demonstrated the effectiveness of an intraocular pressure-lowering drug in patients with glaucoma using visual field progression as a primary outcome. The present study tested the hypothesis that responses on patient-reported outcome measures (PROMs; secondary outcome measure) differ between patients receiving a topical prostaglandin analog (latanoprost) or placebo eye drops in UKGTS. Design Multicenter, randomized, triple-masked, placebo-controlled trial. Participants Newly diagnosed glaucoma patients in the UKGTS with baseline and exit PROMs (n = 182 and n = 168 patients from the treatment and placebo groups, respectively). Methods In the UKGTS (trial registration number, ISRCTN96423140), patients with open-angle glaucoma were allocated to receive latanoprost (treatment) or placebo; the observation period was 24 months. Patients completed general health PROMs (European Quality of Life in 5 Dimensions [EQ-5D] and 36-item Short Form [SF-36]) and PROMs specific to glaucoma (15-item Glaucoma Quality of Life [GQL-15] and 9-item Glaucoma Activity Limitation [GAL-9]) at baseline and exit from the trial. Percentage changes between measurement on PROMs were calculated for each patient and compared between treatment arms. In addition, differences between stable patients (n = 272) and those with glaucomatous progression (n = 78), as determined by visual field change (primary outcome), were assessed. Main Outcome Measure PROMs on health-related and vision-related quality of life. Results Average percentage change on PROMs was similar for patients in both arms of the trial, with no statistically significant differences between treatment and placebo groups (EQ-5D, P = 0.98; EQ-5D visual analog scale, P = 0.88; SF-36, P = 0.94, GQL-15, P = 0.66; GAL-9, P = 0.87). There were statistically significant differences between stable and progressing patients on glaucoma-specific PROMs (GQL-15, P = 0.02; GAL-9, P = 0.02), but not on general health PROMs (EQ-5D, P = 0.62; EQ-5D visual analog scale, P = 0.23; SF-36, P = 0.65). Conclusions Average change in PROMs on health-related and vision-related quality of life was similar for the treatment and placebo groups in the UKGTS. The PROMs used may not be sensitive enough to function as primary end points in clinical trials when participants have newly diagnosed early-stage glaucoma

THE ISOTOPIC SIGNATURE OF THE MINERALIZING FLUID OF THE LAVRION CARBONATE-REPLACEMENT PB-ZN-AG DISTRICT

The Pb-Zn-Ag carbonate-replacement deposits in the Lavrion district are genetically related to a 7- 10 Ma-old granodiorite, felsic dikes and sills. These deposits are hosted in the Upper and Lower marble and schists of the Cyclades Blueschist unit and occur along the major Legraina detachment fault. Carbonate-replacement orebodies occur as “mantos” and veins, dominated by base metal sulfides and Ag, Bi, Sn, Sb, As, and Pb sulfosalts. Calculated carbon and oxygen isotope compositions of the hydrothermal fluid range from δ13CCO2 of -13.7 to 0.8 per mil and δ18OH2O of 4.2 to 27.4 per mil, at 400º, 350º, 320º, 300º, 250º and 200ºC. These isotopic compositions reveal water-torock ratios ranging from 4.8 to 52.6%, which reflect intense interaction of the ore fluid with the host rock in a water-dominated, transitional closed to open hydrothermal system. The range of δ34SH2S for sulfides in the deposits were from -8.5 to 6.8 per mil, for similar temperatures, whereas for barite-fluorite veins from δ34SH2S of -43.6 to -16.4 per mil, at 200º, 150º and 100ºC. This range implies that there was contribution from a magmatic sulfur component exsolved from the Plaka pluton, as well as contribution from a metasedimentary component. Based on the isotopic signature of sulfur for barite, the ranges from -6.7 to -7.6, comprising an increase in the fluid influx. Isotopic temperatures based on pyrite-galena and sphalerite-pyrite pairs revealed at least three major events of carbonate-replacement ore deposition, (i) at ~ 360º, (ii) 320º-280ºand (iii) 260º-200ºC

Values congruence on CSR and its impact on corporate reputation

Corporate Social Responsibility (CSR) is increasingly accepted by decision makers and implemented in businesses, because it is beneficial to an organization’s profit and influence and also the perceptions and commitment of its stakeholders. Therefore, doing CSR is largely related to building a good reputation. Although the individual values of managers is more and more regarded as a driver CSR, and as the congruence between corporate values and employee values is known to impact CSR activities, the link between individual values and Corporate Reputation (CR) is an understudied topic. The purpose of this article is to propose how to investigate this issue in a higher education context. Exploring, a) to what extent university top managers and middle managers values concur in respect of CSR, and b) how this might impact on the CR which is perceived by other stakeholders are its chief focus. The proposed study is to be based on two case study universities, one in the UK and one in China. Both semi-structured interviews and surveys are proposed, representing a mixed methods approach to a complex problem. This study will benefit university top management in its CSR decision making

Problematic practice in integrated impact assessment: the role of consultants and predictive computer models in burying uncertainty

It is well known in impact assessment that predictive model outputs will be as credible as their inputs and that model assumptions will drive outputs. What is less well known is how the practice of integrated impact assessment with its pervasive use of predictive computer models and multiple teams of consultants can influence evidence relied upon in deliberations over the impacts and benefits of major projects. This paper draws on an integrated impact assessment of a major energy infrastructure project in Australia known as Basslink to examine the epistemic implications of current practice. It will be argued that what has become standard procedure can serve to diminish the disclosure of prediction uncertainty

Changes in the Circadian Rhythm in Patients with Primary Glaucoma

Purpose The current study was undertaken to investigate whether glaucoma affects the sleep quality and whether there is any difference between patients with primary glaucoma (primary open angle glaucoma, POAG and primary angle-closure glaucoma, PACG) and healthy subjects, using a validated self-rated questionnaire, the Pittsburgh Sleep Quality Index (PSQI). Methods The sleep quality of patients with POAG and PACG was tested against normal controls. Subjects were divided into three sub-groups according to age. Differences in the frequency of sleep disturbances (PSQI score >7) were assessed. The differences of sleep quality within the three groups and within the POAG group depending on the patients’ intraocular pressure (IOP) and impairment of visual field (VF) were also studied. Results 92 POAG patients, 48 PACG patients and 199 controls were included. Sleep quality declined with age in control and POAG group (tendency chi-square, P0.05). No significant differences were found in POAG group between patients with a highest IOP in daytime and at nighttime (χ2-test, P>0.05). Conclusions The prevalence of sleep disorders was higher in patients with POAG and PACG than in controls. PACG patients seemed to have a more serious problem of sleep disorders than POAG patients between 61 to 80 years old. No correlation was found between the prevalence of sleep disorders and impairment of VF or the time when POAG patients showed a highest IOP

An examination of intentions of recommending fitness centers by user members

The goal of this study was to examine what experiences members have with fitness centers that influence their intentions for recommendation. After item generation and content validity, as well as a pilot test, a survey was conducted among members of five different clubs (n=1750). The questionnaire included measures of service quality attributes, accessibility, well-being in life, well-being in a club, and intentions to recommend a fitness center. Results using a structural equation model provide evidence that only service quality attributes and well-being in a club have positive effect on intentions of users to recommend it. Well-being in life has a negative effect on the intentions for recommendation, while accessibility shows no predictive effect. These findings suggest implications for the management of a club, such as the need to create a pleasant environment and to provide a personalized service directed towards the members’ goals in order to improve well-being in a club and contribute to increase the intentions to recommend the fitness centers to others.O objetivo deste estudo foi examinar como as experiências de usuários de centros de atividade física interferem nas intenções em recomendar serviços. Depois de gerar itens e validar o conteúdo, aplicou-se um pré-teste, o questionário final foi aplicado a sócios de cinco clubes de fitness (n=1.750). O questionário incluiu atributos da qualidade do serviço, acessibilidade, bem-estar na vida, bem-estar no clube e intenção de recomendar. O modelo de equações estruturais mostrou que apenas os atributos da qualidade do serviço e bem-estar no clube têm um efeito positivo sobre as intenções de recomendar. O bem-estar na vida tem um efeito negativo sobre as intenções para recomendar, enquanto que a acessibilidade não mostra nenhum efeito preditivo. Estas conclusões sugerem a necessidade de criar um ambiente agradável nos clubes e de oferecer um serviço personalizado para os objetivos dos sócios, a fim de melhorar o bem-estar no clube e contribuir para a intenção de recomendar o ginásio. Palavras-chave: intenção de recomendar, atributos da qualSin financiación0.191 SJR (2014) Q3, posición 172/231 Health (social science), 1027/1811 Medicine (miscellaneous); Q4, 112/128 Sports scienceUE