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Copy number profiles of paired primary and metastatic colorectal cancers
Get PDFThis is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0
(CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source
are credited.Liver metastasis is the major cause of death following a diagnosis of colorectal cancer (CRC). In this study, we compared the copy number profiles of paired primary and liver metastatic CRC to better understand how the genomic structure of primary CRC differs from the metastasis. Paired primary and metastatic tumors from 16 patients and their adjacent normal tissue samples were analyzed using single nucleotide polymorphism arrays. Genome-wide chromosomal copy number alterations were assessed, with particular attention to 188 genes known to be somatically altered in CRC and 24 genes that are clinically actionable in CRC. These data were analyzed with respect to the timing of primary and metastatic tissue resection and with exposure to chemotherapy. The genomic differences between the tumor and paired metastases revealed an average copy number discordance of 22.0%. The pairs of tumor samples collected prior to treatment revealed significantly higher copy number differences compared to post-therapy liver metastases (P = 0.014). Loss of heterozygosity acquired in liver metastases was significantly higher in previously treated liver metastasis samples compared to treatment naive liver metastasis samples (P = 0.003). Amplification of the clinically actionable genes ERBB2, FGFR1, PIK3CA or CDK8 was observed in the metastatic tissue of 4 patients but not in the paired primary CRC. These examples highlight the intra-patient genomic discrepancies that can occur between metastases and the primary tumors from which they arose. We propose that precision medicine strategies may therefore identify different actionable targets in metastatic tissue, compared to primary tumors, due to substantial genomic differences
Sphingosine-1-Phosphate and the S1P3 Receptor Initiate Neuronal Retraction via RhoA/ROCK Associated with CRMP2 Phosphorylation
Get PDFThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.The bioactive lipid sphingosine-1-phosphate (S1P) is an important regulator in the nervous system. Here, we explored the role of S1P and its receptors in vitro and in preclinical models of peripheral nerve regeneration. Adult sensory neurons and motor neuron-like cells were exposed to S1P in an in vitro assay, and virtually all neurons responded with a rapid retraction of neurites and growth cone collapse which were associated with RhoA and ROCK activation. The S1P1 receptor agonist SEW2871 neither activated RhoA or neurite retraction, nor was S1P-induced neurite retraction mitigated in S1P1-deficient neurons. Depletion of S1P3 receptors however resulted in a dramatic inhibition of S1P-induced neurite retraction and was on the contrary associated with a significant elongation of neuronal processes in response to S1P. Opposing responses to S1P could be observed in the same neuron population, where S1P could activate S1P1 receptors to stimulate elongation or S1P3 receptors and retraction. S1P was, for the first time in sensory neurons, linked to the phosphorylation of collapsin response-mediated protein-2 (CRMP2), which was inhibited by ROCK inhibition. The improved sensory recovery after crush injury further supported the relevance of a critical role for S1P and receptors in fine-tuning axonal outgrowth in peripheral neurons
Effectiveness of a Web 2.0 Intervention to Increase Physical Activity in Real-World Settings: Randomized Ecological Trial
Get PDFThis is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research, is properly cited. The complete bibliographic information, a link to the original publication on http://www.jmir.org/, as well as this copyright and license information must be included.Background: The translation of Web-based physical activity intervention research into the real world is lacking and becoming increasingly important.
Objective: To compare usage and effectiveness, in real-world settings, of a traditional Web 1.0 Web-based physical activity intervention, providing limited interactivity, to a Web 2.0 Web-based physical activity intervention that includes interactive features, such as social networking (ie, status updates, online “friends,” and personalized profile pages), blogs, and Google Maps mash-ups.
Methods: Adults spontaneously signing up for the freely available 10,000 Steps website were randomized to the 10,000 Steps website (Web 1.0) or the newly developed WALK 2.0 website (Web 2.0). Physical activity (Active Australia Survey), quality of life (RAND 36), and body mass index (BMI) were assessed at baseline, 3 months, and 12 months. Website usage was measured continuously. Analyses of covariance were used to assess change over time in continuous outcome measures. Multiple imputation was used to deal with missing data.
Results: A total of 1328 participants completed baseline assessments. Only 3-month outcomes (224 completers) were analyzed due to high attrition at 12 months (77 completers). Web 2.0 group participants increased physical activity by 92.8 minutes per week more than those in the Web 1.0 group (95% CI 28.8-156.8; P=.005); their BMI values also decreased more (–1.03 kg/m2, 95% CI –1.65 to -0.41; P=.001). For quality of life, only the physical functioning domain score significantly improved more in the Web 2.0 group (3.6, 95% CI 1.7-5.5; P<.001). The time between the first and last visit to the website (3.57 vs 2.22 weeks; P<.001) and the mean number of days the website was visited (9.02 vs 5.71 days; P=.002) were significantly greater in the Web 2.0 group compared to the Web 1.0 group. The difference in time-to-nonusage attrition was not statistically significant between groups (Hazard Ratio=0.97, 95% CI 0.86-1.09; P=.59). Only 21.99% (292/1328) of participants (n=292 summed for both groups) were still using either website after 2 weeks and 6.55% (87/1328) were using either website after 10 weeks.
Conclusions: The website that provided more interactive and social features was more effective in improving physical activity in real-world conditions. While the Web 2.0 website was visited significantly more, both groups nevertheless displayed high nonusage attrition and low intervention engagement. More research is needed to examine the external validity and generalizability of Web-based physical activity interventions
The Importance of Community Service Delivery for Mother with Postnatal Depression
Get PDF"reprinted with permission of the Australian Nursing & Midwifery Journal (ANMJ)"The importance of ‘setting’ cannot be underestimated when delivering services to mothers with postnatal depression. Postnatal depression effects the interaction between the infant, mother and family both physically and psychologically (Bergink et al. 2011; Bowen et al. 2013)
Commissioning and equity in primary care in Australia: Views from Primary Health Networks
Get PDFThis article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for selfarchiving. Copyright © 2017 John Wiley & Sons Ltd. All rights reservedThis paper reports findings from 55 stakeholder interviews undertaken in six Primary Health Networks (PHNs) in Australia as part of a study of the impact of population health planning in regional primary health organisations on service access and equity. Primary healthcare planning is currently undertaken by PHNs which were established in 2015 as commissioning organisations. This was a departure from the role of Medicare Locals, the previous regional primary health organisations which frequently provided services. This paper addresses perceptions of 23 senior staff, 11 board members and 21 members of clinical and community advisory councils or health priority groups from six case study PHNs on the impact of commissioning on equity. Participants view the collection of population health data as facilitating service access through redistributing services on the basis of need and through bringing objectivity to decision‐making about services. Conversely, participants question the impact of the political and geographical context and population profile on capacity to improve service access and equity through service commissioning. Service delivery was seen as fragmented, the model is at odds with the manner in which Aboriginal Community Controlled Health Organisations (ACCHOs) operate and rural regions lack services to commission. As a consequence, reliance upon commissioning of services may not be appropriate for the Australian primary healthcare context
Impaired mismatch negativity to frequency deviants in individuals at ultra-high risk for psychosis, and preliminary evidence for further impairment with transition to psychosis
Get PDF© 2018 Elsevier BV. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Background
There is evidence to suggest that people with established psychotic disorders show impairments in the mismatch negativity induced by a frequency-deviant sound (fMMN), and that these impairments worsen with the deterioration of psychotic symptoms. This study aimed to test whether individuals at ultra-high risk (UHR) for psychosis show pre-morbid impairments in fMMN, and if so, whether fMMN continues to deteriorate with transition to psychosis.
Method
fMMN was recorded in a cohort of UHR individuals (n = 42) and compared to healthy controls (n = 29). Of the 27 UHR participants who returned for a second EEG session, six participants had transitioned to psychosis by 12-month follow-up (UHR-T) and were compared to the 21 participants who did not transition (UHR-NT).
Results
fMMN amplitude was significantly reduced, relative to healthy controls, in the UHR cohort. Furthermore, UHR-T individuals showed a significant decrease in fMMN amplitude over the period from baseline to post-transition; this reduction was not observed in UHR-NT.
Conclusions
These results suggest that fMMN is abnormal in UHR individuals, as has repeatedly been found previously in people with established psychotic disorders. The finding that fMMN impairment worsens with transition to psychosis is consistent with the staging model of psychosis; however, caution must be taken in interpreting these findings, given the extremely small sample size of the UHR-T group
Politics, policies and processes: a multidisciplinary and multimethods research programme on policies on the social determinants of health inequity in Australia
Get PDF© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/Introduction The development and implementation of multisectoral policy to improve health and reduce health inequities has been slow and uneven. Evidence is largely focused on the facts of health inequities rather than understanding the political and policy processes. This 5-year funded programme of research investigates how these processes could function more effectively to improve equitable population health.
Methods and analysis The programme of work is organised in four work packages using four themes (macroeconomics and infrastructure, land use and urban environments, health systems and racism) related to the structural drivers shaping the distribution of power, money and resources and daily living conditions. Policy case studies will use publicly available documents (policy documents, published evaluations, media coverage) and interviews with informants (policy-makers, former politicians, civil society, private sector) (~25 per case). NVIVO software will be used to analyse the documents to see how ‘social and health equity’ is included and conceptualised. The interview data will include qualitative descriptive and theory-driven critical discourse analysis. Our quantitative methodological work assessing the impact of public policy on health equity is experimental that is in its infancy but promises to provide the type of evidence demanded by policy-makers.
Ethics and dissemination Our programme is recognising the inherently political nature of the uptake, formulation and implementation of policy. The early stages of our work indicate its feasibility. Our work is aided by a Critical Policy Reference Group. Multiple ethics approvals have been obtained with the foundation approval from the Social and Behavioural Ethics Committee, Flinders University (Project No: 6786).
The theoretical, methodological and policy engagement processes established will provide improved evidence for policy-makers who wish to reduce health inequities and inform a new generation of policy savvy knowledge on social determinants
Development and Validation of a Questionnaire to Measure Attitude change in Health Professionals after Completion of an Aboriginal Health and Cultural Safety Training Programme
No full textCOPYRIGHT: © The Author(s) 2017 subject to the Cambridge Core terms of use.Socially accountable health curricula, designed to decrease Aboriginal health inequities through the transformation of health professional students into culturally safe practitioners, has become a focal point for health professional programmes. Despite this inclusion in health curricula there remains the question of how to best assess students in this area in relation to the concept, of cultural safety and transformative unlearning, to facilitate attitudinal change. To address this question, this study developed a research questionnaire to measure thematic areas of transformative unlearning, cultural safety and critical thinking in Aboriginal Health for application on undergraduate and postgraduate students and faculty staff. The Likert-scale questionnaire was developed and validated through face and content validity. Test–retest methodology was utilised to determine stability and reliability of the questionnaire with 40 participants. The extent of agreement and reliability were determined through weighted kappa and intraclass correlation coefficient. Exploratory factor analysis was calculated to determine construct validity for questionnaire items. For the overall population subset the tool met good standards of reliability and validity, with 11 of the 15 items reaching moderate agreement (κ > 0.6) and an intraclass correlation coefficient of 0.72, suggesting substantial agreement. Cronbach's alpha was calculated above 0.7 for the thematic areas. The majority of items provided high factor loadings, low loading items will be reviewed to strengthen the tool, where validations of the revised tool with a larger cohort will allow future use to compare and determine effective teaching methodologies in Aboriginal health and cultural safety curricula
Assisting Transition: Growth Prospects for the Development of the Assistive Technology Industry in South Australia
Get PDF© [2017] Flinders University / Australian Industrial Transformation InstituteAround the world, but particularly in the advanced Western economies and key Asian economies, populations are ageing, retirees are wealthier than ever before, governments are moving to provide greater assistance to persons with disabilities and new technologies are creating the prospect of longer, more independent, more active and healthy lives. And, of course, the incidence of people with a disability rises in tandem with population ageing.
Individuals and communities are demanding access to assistive technologies (or AT) in line with their higher incomes, requirements for a high quality of life, and the technological innovations that are creating an ever-more vast array of possibilities.
Governments concerned with the rising cost of caring for older persons and those with a disability will support solutions that enable them to be cared for in their homes rather than in dedicated care facilities where the costs are higher. At the same time governments are encouraging older workers to participate in the workforce for as long as possible. Assistive
technologies have an important role to play in facilitating these objectives
Revisiting return to work coordinators. Building bridges 2010-2016
Get PDF© [2017] Flinders University / Australian Industrial Transformation InstituteEffective from 1 January 2009, employers with 30 employees or more were legislatively required to appoint rehabilitation and return to work (RTW) coordinators (“Coordinators”) in South Australia. This decision followed the Clayton Review of the worker’s compensation system with Coordinators responsible for the organisation’s internal management of work-related injuries and the rehabilitation and return to work of injured employees.
The year following the implementation of the legislation, in 2010, the team from the Australian Industrial Transformation Institute (AITI)1 conducted a survey of 570 Coordinators for RTWSA2 (Hordacre, Katterl, Chiveralls, Barnett, & Spoehr, 2010). The online survey explored the demographic and workplace characteristics of Coordinators, the perceived efficacy of their training and professional development activities, the value placed on the role by organisations, barriers to RTW, and usefulness of strategies to promote RTW in the workplace.
Six years on RTWSA sought to repeat the survey in order to: Compare the characteristics and perceptions of Coordinators in 2010 and 2016; Understand their experiences, organisational role and the way they engage with injured workers; Examine what has worked in the six years since their inception; Explore other challenges that have emerged over this time; and Clarify how the new RTW Act will impact on the function of Coordinators in the workplace and within the scheme