Development of an In Vitro Assay to Predict Patient Response to Radiotheraphy

At the present time, the treatment plan for a patient with cancer is usually based on parameters such as tumour site, histological type, and tumour stage and performance status. However, it is well know that the radiosensitivity of human cancers varies widely from one patient to another (Fertil et al., 1981), and that even within these broad categories some tumours will show greater response to radiotherapy than others. If those patients unlikely to be cured by radiotherapy could be identified prior to commencement of treatment, alternative or more aggressive therapies might be selected which may give a better chance of cure than the standard therapy. The aim of this study was to develop an in vitro essay, the Mothersill outgrowth assay, to predict the individual patient response to chemo – and, in particular, radiotherapy. This assay involves culturing explants cut from a tumour and then treating them in situ with clinical equivalent doses of chemo- and radiotherapy. Two type of cancer were examined, oesophageal carcinoma and head and neck squamous cell carcinoma. The sensitivity of the tumour to treatment was evaluated in terms of the % growth inhibition in the treated cultures relative to the untreated control. The nature of this assay allowed other parameters to be examined immunocytochemically as potential indicators of tumour radiosensitivity. These parameters have previously been shown to be of prognostic significance in a range of cancers, they include: % Ki67 positive cells: expression of EGFr, c-Myc and BCl-2: co-express ion of c-Myc and Bcl-2: expression of the non-functional protein product of p53. The Mothersill outgrowth assay provided a system in which multiple parameters could be examined from limited tumour material. Due to the small patient number conclusive results could not be obtained regarding the parameter, % growth inhibition, as an indicator of patient response to treatment. To obtain these results a larger time scale would be required to allow for the accumulation of a large number of patients and a long follow up time. The results obtained indicated that % Ki67 positive cells measured after irradiation was indicative of patient in vitro radiosensitivity; expression of Ki67 correlated positively with radiosensitivity. EGFr expression measured before and after treatment differentiated the radio-sensitive and resistant tumours. High expression of EGRf correlated with radio-resistance. Express of c-Myc and Bcl-2 taken alone did not indicate tumour sensitivity, however tumours positive for c-Myc and negative for Bcl-2 were radiosensitive. Express of p53 protein did not significantly differentiate the radio- sensitive and resistant head and neck squamous cell carcinoma tumours, although when examined in cell lines derived from colorectal and bladder tumours, a significant correlation was found between radiosensitivity and p53 protein expression; high % of p53 positive cells correlated with radio-resistance. In conclusion, using the Mothersill assay it was possible to evaluate several parameters from a limited amount of tissues. Of these parameters, % Ki67, EGFr, c-Myc and Bcl-2 appear to have potential as indicators of tumour radiosensitivity. An increase in the number of head and neck squamous cell carcinoma patients and a longer follow up time will be required before any conclusions can be made regarding the potential of the parameter, % growth inhibition, to predict patient response to treatment

Smokejumper Magazine, July 2007

This issue of the National Smokejumper Association (NSA) Smokejumper Magazine contains the following articles: Hook Before You Leap (malfunction on fire jump), Troop, Jerry vs Slave Traders (rescue of sister-in-law), D.B. Cooper (Sheridan Peterson), Vietnam: A Country Moving Forward (Mary Pickett), Legendary Pilot Ken Roth Dies. Profile T.J. Thompson. Smokejumper Magazine continues Static Line, which was the original title of the NSA quarterly magazine.https://dc.ewu.edu/smokejumper_mag/1055/thumbnail.jp

Building Infrastructures for Community Engagement at the University of Louisville: Graduate Models for Cultivating Stewardship

From our perspectives at the University of Louisville, we address the need to provide structures for graduate student participation in community-engaged scholarship. Architectures of participation such as the ones we describe in this piece—the Community Engagement Academy and the Digital Media Academy—offer graduate students the opportunity to practice designing and implementing community engagement projects within interdisciplinary and disciplinary sites. The models we provide were designed to make the invisible work of community engagement visible and to create low barriers of entry for graduate students to become stewards of their disciplines as well as stewards of their communities. Such opportunities, we argue, help promote a more capacious view of stewardship, and thus encourage emerging engaged scholars to learn how to act responsibly and wisely in conducting communityengaged research

Mothers\u27 Ways of Making It—or Making Do?: Making (Over) Academic Lives in Rhetoric and Composition with Children

This article focuses on five women\u27s experiences “making it” as rhetoricians with children. Expanding the definition of success Michelle Ballif, Diane Davis and Roxanne Mountford set forth in Women\u27s Ways of Making It in Rhetoric and Composition, the article offers suggestions for moving toward more family-friendly academic structures, not least by recognizing that the seemingly individualistic idea of choice—such as the choice to have children—rests uneasily with the often invisible structures that shape and delimit choices. The authors call for increased visibility of and acceptance for a greater range of possibilities for “making it” in the field today

The Working World of Nursing Unit Managers

Nursing unit managers (NUMs) occupy a first-line management position in many healthcare services worldwide. In this role, they are responsible for the nursing and administrative operations of a ward. The literature suggests that while the position has evolved into a complex and multifaceted one, the scope and authority of the role are poorly understood. Few studies have explored the working world of NUMs or considered how the well-documented oppression of nurses might impact on them as managers. Using a feminist approach, and individual interviews, this qualitative study, which focused on the construct of power, explored the working world of twenty nursing unit managers employed in the public healthcare system of New South Wales, Australia

Merger Success Factors - An Examination of the Australian Not-for-Profit Aged and Community Care Sector

This research investigated the drivers and success factors for mergers in the Australian not-­for-­profit aged and community care sector. In response to increased demand for aged and community care services and changing expectations of an ageing population, the Australian government is embarking on significant national health reforms to deliver a more market driven service. For a sector dominated by the not-­for-­profit providers, this new competitive paradigm will be an industry shock of such magnitude that it will transform how the sector operates in the future. A literature review of the corporate and health sector confirmed that restructure through mergers is one way for a sector to adapt to industry shocks. An examination of the national profile of the Australian aged and community care sector confirmed that mergers are occurring. Between 2003 and 2010, the sector consolidated by 10% whilst the number of operational services/outlets increased by 23%. The drivers and success factors of mergers in the sector were investigated by drawing on data from an online questionnaire of the not-­for-­profit aged and community care providers in NSW and ACT, as well as in-­depth interviews of six industry CEOs. Mergers and amalgamations are perceived to deliver financial sustainability and allow organisations to position themselves strategically, enabling organisations to adapt to the industry shock of the national health reforms and deliver better client outcomes. The literature review and data collected from CEO interviews emphasised hat post-merger integration is critical in realising the anticipated merger gains. This research demonstrated that the industry will be required to balance the tension between external environmental forces, internal governance activities and internal relationship challenges to maximise the probability of a successful merger

The iHOPE-20 study: relationships between and prospective predictors of remission, clinical recovery, personal recovery and resilience 20 years on from a first episode psychosis

peer-reviewedObjective: Knowledge of outcome in psychotic illness is limited by the paucity of very long-term epidemiologically representative studies of incidence first episode psychosis (FEP) cohorts that measure and compare outcomes reflecting modern clinical practice, mental health policy and research agendas. Our study aimed to address this gap. Method: iHOPE-20 is a prospective 20-year follow-up study of a FEP incidence cohort (N = 171) conducted between 2014 and 2017 in Ireland. Data from previous studies and medical records were used to recruit cohort members. We assessed remission, clinical recovery, personal recovery and resilience at 20 years; explored the relationships between these outcomes and examined the predictive value of baseline characteristics in determining them. Results: At follow-up, 20 out of 171 cohort members (11.70%) were deceased. We assessed 80 out of 151 alive cohort members (53% recruitment rate); 65% were in remission; 35.2% were in Full Functional Recovery and 53.7% confirmed they were fully recovered according to their personal definition of recovery. A complex array of relationships between outcomes was found. Outcomes were better for people who had a short duration of untreated psychosis, displayed higher premorbid social adjustment (between the ages of 5–11) and at baseline, were older, not living alone, in full-time employment, given a non-affective diagnosis, and had lower Global Assessment of Functioning scores. Conclusion: Among participants, full remission of psychotic symptoms and personally defined recovery was not just possible but likely in the very long term. However, attaining positive functional outcomes and building resilience in FEP remain key challenges for mental health services.PUBLISHEDpeer-reviewe

Hippocampal Contribution to Context Encoding across Development Is Disrupted following Early-Life Adversity

Context can drastically influence responses to environmental stimuli. For example, a gunshot should provoke a different response at a public park than a shooting range. Little is known about how contextual processing and neural correlates change across human development or about individual differences related to early environmental experiences. Children (N = 60; 8–19 years, 24 exposed to interpersonal violence) completed a context encoding task during fMRI scanning using a delayed match-to-sample design with neutral, happy, and angry facial cues embedded in realistic background scenes. Outside the scanner, participants completed a memory test for context-face pairings. Context memory and neural correlates of context encoding did not vary with age. Larger hippocampal volume was associated with better context memory. Posterior hippocampus was recruited during context encoding, and greater activation in this region predicted better memory for contexts paired with angry faces. Children exposed to violence had poor memory of contexts paired with angry faces, reduced hippocampal volume, and atypical neural recruitment on encoding trials with angry faces, including reduced hippocampal activation and greater functional connectivity between hippocampus and ventrolateral prefrontal cortex (vlPFC). Greater hippocampus-vlPFC connectivity was associated with worse memory for contexts paired with angry faces. Posterior hippocampus appears to support context encoding, a process that does not exhibit age-related variation from middle childhood to late adolescence. Exposure to dangerous environments in childhood is associated with poor context encoding in the presence of threat, likely due to greater vlPFC-dependent attentional narrowing on threat cues at the expense of hippocampus-dependent processing of the broader context