Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative

This study aimed to investigate whether molecular analysis can be used to refine risk assessment, direct adjuvant therapy, and identify actionable alterations in high-risk endometrial cancer. TransPORTEC, an international consortium related to the PORTEC3 trial, was established for translational research in high-risk endometrial cancer. In this explorative study, routine molecular analyses were used to detect prognostic subgroups: p53 immunohistochemistry, microsatellite instability and POLE proofreading mutation. Furthermore, DNA was analyzed for hotspot mutations in 13 additional genes (BRAF, CDKNA2, CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, and PTEN) and protein expression of ER, PR, PTEN, and ARID1a was analyzed. Rates of distant metastasis, recurrence-free, and overall survival were calculated using the Kaplan-Meier method and log-rank test. In total, samples of 116 high-risk endometrial cancer patients were included: 86 endometrioid; 12 serous; and 18 clear cell. For endometrioid, serous, and clear cell cancers, 5-year recurrence-free survival rates were 68%, 27%, and 50% (P=0.014) and distant metastasis rates 23%, 64%, and 50% (P=0.001), respectively. Four prognostic subgroups were identified: (1) a group of p53-mutant tumors; (2) microsatellite instable tumors; (3) POLE proofreading-mutant tumors; and (4) a group with no specific molecular profile (NSMP). In group 3 (POLE-mutant; n=14) and group 2 (microsatellite instable; n=19) patients, no distant metastasis occurred, compared with 50% distant metastasis rate in group 1 (p53-mutant; n=36) and 39% in group 4 (NSMP; P<0.001). Five-year recurrence-free survival was 93% and 95% for group 3 (POLE-mutant) and group 2 (microsatellite instable) vs 42% (group 1, p53-mutant) and 52% (group 4, NSMP; P<0.001). Targetable FBXW7 and FGFR2 mutations (6%), alterations in the PI3K-AKT pathway (60%) and hormone receptor positivity (45%) were frequently found. In conclusion, molecular analysis of high-risk endometrial cancer identifies four distinct prognostic subgroups, with potential therapeutic implications. High frequencies of targetable alterations were identified and may serve as targets for individualized treatment

Attributions of responsibility, blame and justifiability to a perpetrator and victim in an acquaintance rape scenario: The influence of Marijuana intoxication

Marijuana is a commonly used illicit drug by young adults and has been implicated in about one third of sexual assaults. However, the influence of Marijuana intoxication on rape attributions has not been previously investigated. This study examined the effects of perpetrator and victim Marijuana intoxication and participant sex on rape attributions. Young adults (N = 285) read an acquaintance rape scenario where Marijuana intoxication was manipulated and completed measures of perpetrator (responsibility, blame and justifiability) and victim attributions (responsibility and blame). The results revealed that an intoxicated, compared to sober, perpetrator was attributed less responsibility for his sexual aggression. When the victim was intoxicated, compared to sober, the perpetrator and victim were attributed less and more blame for the assault, respectively. These findings demonstrate that, irrespective of perceiver sex, Marijuana intoxication, like alcohol intoxication, results in an attributional double standard in favour of the perpetrator.

Recruiting and retaining plasmapheresis donors: A critical belief analysis

This paper identifies critical beliefs underpinning intentions to commence and continue plasmapheresis donation. Whole blood (n = 624) and first-time plasmapheresis (n = 460) donors completed a cross-sectional survey assessing the belief-base of the theory of planned behaviour and rated their plasmapheresis donation intentions. While the idea of red blood cells being returned was a key deterrent for all donors, critical beliefs underlying commencement and continuation in the plasmapheresis donor panel differed and varied as a function of blood donation history. Findings will assist the development of targeted persuasion messages to optimise recruitment and retention of plasmapheresis donors in a non-remunerated context.

The characterisation of Ureaplasma species isolated from the Chorioamnion of women who deliver late Preterm

This thesis investigated, for the first time, the prevalence of Ureaplasma species infection within the placentae of women who delivered in the late preterm stages of pregnancy. The presence of these microorganisms was associated with either severe inflammation within the placenta or, for some women, there were no pregnancy complications and these women delivered at term. Ureaplasmas are able to vary their surface exposed lipoproteins and we demonstrated that different host immune responses were generated in vivo to different sized surface lipoproteins. This may explain why ureaplasma infections do not always result in adverse pregnancy and neonatal outcomes.

Have you got what it takes? Nursing in a Psychiatric Intensive Care Unit

Purpose A Psychiatric Intensive Care Unit (PICU) and or High Dependency Unit (HDU) is a locked, intensive treatment facility available to people experiencing acute psychiatric distress. For many people who access public mental health services in Australia, the PICU/HDU is the primary point of admission, and should represent and facilitate timely assessment and an optimum treatment plan under a recovery framework. Nurses are the largest health discipline working in this specialty area of care. The paper aims to discuss these issues. Design/methodology/approach A qualitative study aimed to investigate the skills, experience, and practice, of nurses working in the PICU/HDU in relation to a recovery model of care. Identifying how nurses provide care in the PICU/HDU will inform a clinical practice guideline to further support this specialty area of care. Four focus groups were facilitated with 52 registered nurses attending. Findings The nurse participants identified specific skills under four distinct themes; Storytelling, Treatment and recovery, Taking responsibility, and Safeguarding. The skills highlight the expertise and clinical standard required to support a recovery model of care in the PICU. Research limitations/implications – The research findings highlight urgency for a National PICU/HDU clinical practice guideline. Practical implications A PICU/HDU practice guideline will promote the standard of nursing care required in the PICU/HDU. The PICU/HDU needs to be recognised as a patient centred, therapeutic opportunity as opposed to a restrictive and custodial clinical area. Social implications Providing transparency of practice in the PICU/HDU and educating nurses to this specialty area of care will improve client outcome and recovery. Originality/value Very few studies have explored the skills, experience, and practice, of nurses working in the PICU/HDU in relation to a recovery model of care. A dearth of research exists on what is required to work in this specialty area of care.

Physical activity and screen-time of childhood hematopoietic stem cell transplant survivors

Aim Reduced bone mineral density, impaired cardiovascular fitness, and increased risk of obesity are well-known late effects of Hematopoietic Stem Cell Transplantation (HSCT) in survivors of childhood cancer. These comorbidities can be mitigated through physical activity and limiting screen-time (ST). This study aims to increase the understanding of physical activity and ST behaviours for children following HSCT. Method Children were recruited from two oncology follow-up clinics and completed a questionnaire on their physical activity levels and screen-time. Children were classified as short (≤2yrs) and long term (>2yrs) survivors. Results Fifty-eight children were eligible, of whom forty children age 6 to 18 years (60% males) participated in the study. Less than half (47.5%) met the daily recommendations for physical activity and one third met the ST recommendations. Late survivors reported higher daily physical activity and less ST than early survivors. Among late survivors, females reported higher daily physical activity and less ST than males. Conclusions Our findings suggest that the majority of children following HSCT were not sufficiently active and had excessive screen-time; however this was comparable to healthy populations. Appropriately designed physical activity and screen-time intervention programs should be explored early following transplant for children undergoing HSCT.

The YOU CALL-WE CALL randomized clinical trial: Impact of a multimodal support intervention after a mild stroke

Background Comparison of a multimodal intervention WE CALL (study initiated phone support/information provision) versus a passive intervention YOU CALL (participant can contact a resource person) in individuals with first mild stroke. Methods and Results This study is a single-blinded randomized clinical trial. Primary outcome includes unplanned use of health services (participant diaries) for adverse events and quality of life (Euroquol-5D, Quality of Life Index). Secondary outcomes include planned use of health services (diaries), mood (Beck Depression Inventory II), and participation (Assessment of Life Habits [LIFE-H]). Blind assessments were done at baseline, 6, and 12 months. A mixed model approach for statistical analysis on an intention-to-treat basis was used where the group factor was intervention type and occasion factor time, with a significance level of 0.01. We enrolled 186 patients (WE=92; YOU=94) with a mean age of 62.5±12.5 years, and 42.5% were women. No significant differences were seen between groups at 6 months for any outcomes with both groups improving from baseline on all measures (effect sizes ranged from 0.25 to 0.7). The only significant change for both groups from 6 months to 1 year (n=139) was in the social domains of the LIFE-H (increment in score, 0.4/9±1.3 [95% confidence interval, 0.1–0.7]; effect size, 0.3). Qualitatively, the WE CALL intervention was perceived as reassuring, increased insight, and problem solving while decreasing anxiety. Only 6 of 94 (6.4%) YOU CALL participants availed themselves of the intervention. Conclusions Although the 2 groups improved equally over time, WE CALL intervention was perceived as helpful, whereas YOU CALL intervention was not used.

Study protocol of the YOU CALL - WE CALL TRIAL: Impact of a multimodal support intervention after a "mild" stroke

Background More than 60% of new strokes each year are "mild" in severity and this proportion is expected to rise in the years to come. Within our current health care system those with "mild" stroke are typically discharged home within days, without further referral to health or rehabilitation services other than advice to see their family physician. Those with mild stroke often have limited access to support from health professionals with stroke-specific knowledge who would typically provide critical information on topics such as secondary stroke prevention, community reintegration, medication counselling and problem solving with regard to specific concerns that arise. Isolation and lack of knowledge may lead to a worsening of health problems including stroke recurrence and unnecessary and costly health care utilization. The purpose of this study is to assess the effectiveness, for individuals who experience a first "mild" stroke, of a sustainable, low cost, multimodal support intervention (comprising information, education and telephone support) - "WE CALL" compared to a passive intervention (providing the name and phone number of a resource person available if they feel the need to) - "YOU CALL", on two primary outcomes: unplanned-use of health services for negative events and quality of life. Method/Design We will recruit 384 adults who meet inclusion criteria for a first mild stroke across six Canadian sites. Baseline measures will be taken within the first month after stroke onset. Participants will be stratified according to comorbidity level and randomised to one of two groups: YOU CALL or WE CALL. Both interventions will be offered over a six months period. Primary outcomes include unplanned use of heath services for negative event (frequency calendar) and quality of life (EQ-5D and Quality of Life Index). Secondary outcomes include participation level (LIFE-H), depression (Beck Depression Inventory II) and use of health services for health promotion or prevention (frequency calendar). Blind assessors will gather data at mid-intervention, end of intervention and one year follow up. Discussion If effective, this multimodal intervention could be delivered in both urban and rural environments. For example, existing infrastructure such as regional stroke centers and existing secondary stroke prevention clinics, make this intervention, if effective, deliverable and sustainable.

Plant species’ origin predicts dominance and response to nutrient enrichment and herbivores in global grasslands

Exotic species dominate many communities; however the functional significance of species’ biogeographic origin remains highly contentious. This debate is fuelled in part by the lack of globally replicated, systematic data assessing the relationship between species provenance, function and response to perturbations. We examined the abundance of native and exotic plant species at 64 grasslands in 13 countries, and at a subset of the sites we experimentally tested native and exotic species responses to two fundamental drivers of invasion, mineral nutrient supplies and vertebrate herbivory. Exotic species are six times more likely to dominate communities than native species. Furthermore, while experimental nutrient addition increases the cover and richness of exotic species, nutrients decrease native diversity and cover. Native and exotic species also differ in their response to vertebrate consumer exclusion. These results suggest that species origin has functional significance, and that eutrophication will lead to increased exotic dominance in grasslands.

Application of fragment-based screening to the design of inhibitors of Escherichia coli DsbA

The thiol-disulfide oxidoreductase enzyme DsbA catalyzes the formation of disulfide bonds in the periplasm of Gram-negative bacteria. DsbA substrates include proteins involved in bacterial virulence. In the absence of DsbA, many of these proteins do not fold correctly, which renders the bacteria avirulent. Thus DsbA is a critical mediator of virulence and inhibitors may act as antivirulence agents. Biophysical screening has been employed to identify fragments that bind to DsbA from Escherichia coli. Elaboration of one of these fragments produced compounds that inhibit DsbA activity in vitro. In cell-based assays, the compounds inhibit bacterial motility, but have no effect on growth in liquid culture, which is consistent with selective inhibition of DsbA. Crystal structures of inhibitors bound to DsbA indicate that they bind adjacent to the active site. Together, the data suggest that DsbA may be amenable to the development of novel antibacterial compounds that act by inhibiting bacterial virulence.

Designing a mobile social tool that moderates drinking

A novel mobile social networking tool uses peer support to facilitate responsible drinking among young women. Focus group reports indicate that the tool’s design is easy to use and its functionalities would help peers reduce risk during drinking sessions.

The paradox of creative uncertainty in learning and teaching

In an ever-changing and globalised world there is a need for higher education to adapt and evolve its models of learning and teaching. The old industrial model has lost traction, and new patterns of creative engagement are required. These new models potentially increase relevancy and better equip students for the future. Although creativity is recognised as an attribute that can contribute much to the development of these pedagogies, and creativity is valued by universities as a graduate capability, some educators understandably struggle to translate this vision into practice. This paper reports on selected survey findings from a mixed methods research project which aimed to shed light on how creativity can be designed for in higher education learning and teaching settings. A social constructivist epistemology underpinned the research and data was gathered using survey and case study methods. Descriptive statistical methods and informed grounded theory were employed for the analysis reported here. The findings confirm that creativity is valued for its contribution to the development of students’ academic work, employment opportunities and life in general; however, tensions arise between individual educator’s creative pedagogical goals and the provision of institutional support for implementation of those objectives. Designing for creativity becomes, paradoxically, a matter of navigating and limiting complexity and uncertainty, while simultaneously designing for those same states or qualities.

Investigation of the relationship between BMI and prostate motion in radiation therapy treatment for prostate cancer

This thesis studied the influence of patient obesity on prostate motion during radiation therapy treatment delivery, an important consideration in the accurate treatment of prostate cancer. The study highlighted the importance of daily image guidance to correct for prostate motion, increasing radiation dose to the prostate while decreasing radiation dose to surrounding healthy tissues, thereby increasing patient quality of life.

Stone baby: An exploration of trembling and its potential for visual art

Informed by Kristeva's formulation of affect and Winnicott's Holding Environment, this practice-led visual art project is an exploration into how sensitivity to the physical sensation of trembling can sustain a creative practice. Building upon this is a further enquiry into what the significance of the affective experience of trembling is for an ethics of affect in contemporary art. I have done this through object and video-based installations informed by my own experience of trembling. This has been further informed by the work of artists like Louise Bourgeois, Dennis Del Favero and Willie Doherty. The creative outcomes contribute to the discourse around ethical responses to affect by extending and developing on the works of these artists.

Atmospheres : Aesthetics of emotional spaces[Review]

More problematic than his avoidance of recent geographic scholarship is his treatment of indigenous, ethnographic and postcolonial perspectives on island life. Not only is much of this scholarship absent, the bits that are there are mostly derided. He slams Kamau Braithwaite and his concept of ‘tidalectics’ as ‘unpackable’ (p. 20) and also claims that Greg Dening’s approach to islands as having ‘permeable cultural boundaries’ has ‘intellectual costs’ (p. 23). In a section of the book on ‘Naming and Sovereignty’, instead of an in-depth examination of the processes of decoding and recoding that goes on in indigenous island landscapes under colonialism (as could be discussed at length if Shell chose to examine Aotearoa, Hawaii, or hundreds of other places) we are instead presented a vignette about his childhood street fights with other kids over the naming of a hometown island in Canada, as well as ruminations about what Herman Melville and Ellen Semple thought of islands in the nineteenth century. In short, if you want to know what dead Caucasians like Shakespeare, Melville, Kant, Mackinder, More, and ancient Athenians thought about islands, then this book is a good resource. If, however, you are looking for information about what islands are like today – and what they mean to the people who live on and interact with them – then you will have to look elsewhere.