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    Implementation of an evidence-based intervention to improve the wellbeing of people with dementia and their carers: study protocol for ‘Care of People with dementia in their Environments (COPE)’ in the Australian context

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    © The Author(s). 2018 This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Abstract Background There are effective non-pharmacological treatment programs that reduce functional disability and changed behaviours in people with dementia. However, these programs (such as the Care of People with dementia in their Environments (COPE) program) are not widely available. The primary aim of this study is to determine the strategies and processes that enable the COPE program to be implemented into existing dementia care services in Australia. Methods This study uses a mixed methods approach to test an implementation strategy. The COPE intervention (up to ten consultations with an occupational therapist and up to two consultations with a nurse) will be implemented using a number of strategies including planning (such as developing and building relationships with dementia care community service providers), educating (training nurses and occupational therapists in how to apply the intervention), restructuring (organisations establishing referral systems; therapist commitment to provide COPE to five clients following training) and quality management (coaching, support, reminders and fidelity checks). Qualitative and quantitative data will contribute to understanding how COPE is adopted and implemented. Feasibility, fidelity, acceptability, uptake and service delivery contexts will be explored and a cost/benefit evaluation conducted. Client outcomes of activity engagement and caregiver wellbeing will be assessed in a pragmatic pre-post evaluation. Discussion While interventions that promote independence and wellbeing are effective and highly valued by people with dementia and their carers, access to such programs is limited. Barriers to translation that have been previously identified are addressed in this study, including limited training opportunities and a lack of confidence in clinicians working with complex symptoms of dementia. A strength of the study is that it involves implementation within different types of existing services, such as government and private providers, so the study will provide useful guidance for further future rollout. Trial registration 16 February 2017; ACTRN12617000238370

    Real time monitoring and quantification of reactive oxygen species in breast cancer cell line MCF-7 by 2′,7′–dichlorofluorescin diacetate (DCFDA) assay

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    Published by Elsevier Inc. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (April 2018) in accordance with the publisher’s archiving policyThe detection of reactive oxygen species (ROS) using 2′,7′–dichlorofluorescin diacetate (DCFDA) is commonly performed by a single measurement of fluorescence but this fails to capture a profile of ROS generation over time. This study aimed to develop a real-time monitoring method to increase the utility of the assay, to incorporate cytotoxicity screening and to describe the combined effects of DCFDA and the ROS generator, Ter-butyl hydrogen peroxide (TBHP). Breast cancer MCF-7 cells were loaded with DCFDA (0-50 μM) for 45 min, and then exposed to TBHP (0-50 μM). Fluorescence was recorded according to three different schedules: every hour for 6 h, or once after 6 h or 24 h. Viability was assessed in a crystal violet assay and cell morphology was examined by microscopy. TBHP caused a time and dose-dependent increase in ROS and the magnitude of the fluorescent signal was affected by the loading concentration of DCFDA. Reading the fluorescence every hour for 6 h did not diminish the emission signal. The most sensitive and reliable combination for this ROS assay was 10 μM DCFDA with 25 μM TBHP; since higher concentrations of DCFDA compromised cell viability. In conclusion we adapted a single point ROS assay to enable production of a profile of ROS generation over an extended 6 h period, and related this to cell viability and morphology

    A systematic review and meta-analysis of cognitive processing deficits associated with body dysmorphic disorder

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    © 2018 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 24 month embargo from date of publication (May 2018) in accordance with the publisher’s archiving policyThis systematic review and meta-analysis examined the evidence supporting the association between body dysmorphic disorder (BDD) symptomology and four types of cognitive processing abnormalities: local processing, selective attention, interpretive biases, and memory deficits. Twenty-three studies met inclusion requirements that examined differences in performance on cognitive tasks between BDD and control groups across the four categories. Multilevel modelling was used to calculate an overall effect size for each cognitive category. BDD and control groups differed significantly on measures of selective attention (g=.60, 95% CI=.26: .93), interpretive biases (g=.30, 95% CI=. 07: .54), and memory deficits (g=.56, 95% CI=.26: .87). Differences between the BDD and control groups on measures of local processing did not reach significance. These findings support the hypothesis that people with BDD may selectively attend to perceived threats or to disorder-related stimuli, misinterpret ambiguous stimuli as threatening, overvalue the importance of attractiveness, and have inaccurate coding and recall for facial or bodily stimuli. Recommendations for future research of these specific cognitive deficits in BDD include introducing the use of Modified Dot Probe Paradigms and new treatment targets that can be used as adjuncts to current treatment modalities

    Involvement in Bullying During High School: A Survival Analysis Approach

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    © 2018 Springer Publishing Company. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (June 2018) in accordance with the publisher’s archiving policyKnowledge about the risks of bullying involvement during any year of high school is an important element of interventions for changing the likelihood of being bullied. Three cohorts of Australian students (n = 1,382) were tracked from 7th grade to 11th grade. The study showed that some students continue their involvement in bullying, while in addition, new bullies and new victims emerge during each high school year. The findings indicated that the risk of bullying involvement ranged from 16% (as a bully) to 36% (as a victim), increasing to 54.5% and 56.3%, respectively, if a student was a bully or a victim in 7th grade. The risk to students of becoming victims, bullies, or bully–victims in each year of high school suggests that bullying prevention initiatives should be designed to suit students at different stages of adolescent development

    Electron impact ionization of 1-butanol: I. Mass spectra and partial ionization cross sections

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    © 2018 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 24 month embargo from date of publication (March 2018) in accordance with the publisher’s archiving policy.Experimental measurements of the cations created through electron impact ionization have been undertaken for the primary isomer of butanol, using a Hiden Quadrupole Mass Spectrometer (EPIC 300) with a mass resolution of 1 amu. The mass spectrum recorded at an incident electron energy of 70 eV, normalized and placed on an absolute scale, reveals the relative probability of forming 76 different cations of butanol by either direct ionization or dissociative ionization. Individual partial ionization cross sections (PICS) for the 38 main cationic fragments, measured at electron energies in the range 10–100 eV, are also reported for the first time in this work

    Web-based intervention to improve quality of life in late stage bipolar disorder (ORBIT): randomised controlled trial protocol

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    This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background The primary objective of this randomised controlled trial (RCT) is to establish the effectiveness of a novel online quality of life (QoL) intervention tailored for people with late stage (≥ 10 episodes) bipolar disorder (BD) compared with psychoeducation. Relative to early stage individuals, this late stage group may not benefit as much from existing psychosocial treatments. The intervention is a guided self-help, mindfulness based intervention (MBI) developed in consultation with consumers, designed specifically for web-based delivery, with email coaching support. Methods/design This international RCT will involve a comparison of the effectiveness and cost-effectiveness of two 5-week adjunctive online self-management interventions: Mindfulness for Bipolar 2.0 and an active control (Psychoeducation for Bipolar). A total of 300 participants will be recruited primarily via social media channels. Main inclusion criteria are: a diagnosis of BD (confirmed via a phone-administered structured diagnostic interview), no current mood episode, history of 10 or more mood episodes, no current psychotic features or active suicidality, under the care of a medical practitioner. Block randomisation will be used for allocation to the interventions, and participants will retain access to the program for 6 months. Evaluations will be conducted at pre- and post- treatment, and at 3- and 6- months follow-up. The primary outcome measure will be the Brief Quality of Life in Bipolar Disorder Scale (Brief QoL.BD), collected immediately post-intervention at 5 weeks (T1). Secondary measures include BD-related symptoms (mania, depression, anxiety, stress), time to first relapse, functioning, sleep quality, social rhythm stability and resource use. Measurements will be collected online and via telephone assessments at baseline (T0), 5 weeks (T1), three months (T2) and six months (T3). Candidate moderators (diagnosis, anxiety or substance comorbidities, demographics and current treatments) will be investigated as will putative therapeutic mechanisms including mindfulness, emotion regulation and self-compassion. A cost-effectiveness analysis will be conducted. Acceptability and any unwanted events (including adverse treatment reactions) will be documented and explored. Discussion This definitive trial will test the effectiveness and cost-effectiveness of a novel QoL focused, mindfulness based, online guided self-help intervention for late stage BD, and investigate its putative mechanisms of therapeutic action.This trial is funded by the Australian National Health and Medical Research Council (NHMRC; APP1102097). Funding is augmented by Swinburne University of Technology, the host organisation and the location of the HREC from which ethical approval was sought. MB is supported by an NHMRC Senior Principal Research Fellowship (APP1059660). GM has received Project Grant funding from the NHMRC, beyondblue and CIHR, and personal fees from Servier and CSL biotherapies. SC has received funding from NHMRC, beyondblue, Movember, Stanley Medical Research Institute, and American Foundation for Suicide Prevention

    Changes in foot pain, structure and function following bariatric surgery

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    This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background Bariatric surgery candidates have a high prevalence of foot pain, depression and elevated plantar pressures. There is, however, limited research into how these factors interact pre- and post-surgery. The aims of this study were therefore to investigate the mechanical and non-mechanical factors associated with foot pain severity before, and the change after, surgery. Methods Bariatric surgery candidates underwent baseline and six-month follow-up measures. Foot pain was measured with the Manchester-Oxford Foot Questionnaire. Mechanical measures included body mass index (BMI), dynamic plantar pressures, radiographic foot posture, and hindfoot range of motion. Depressive symptoms, the non-mechanical measure, were assessed by questionnaire. Multivariable linear regression was used to determine which variables were associated with foot pain at baseline and at follow-up. Multilevel repeated models assessed the associations between foot pain and plantar pressure, adjusting for the interaction between group and follow-up time. Results Forty-five participants (84% female), with mean (SD) age of 45.7 (9.4) years were recruited. Twenty-nine participants had bariatric surgery and 16 participants remained on the waiting list (controls). Following bariatric surgery, foot pain reduced significantly by - 35.7 points (95% CI -42.2 to - 28.8), while depressive symptoms and whole foot peak pressures had a significant mean change of - 5.9 points (95% CI -10.3 to - 1.5) and - 36 kPa (95% CI -50 to - 22), respectively. In multivariable analysis, depressive symptoms were associated with foot pain at baseline β = 0.7 (95% CI 0.2 to 1.2) after controlling for age, gender, BMI, foot posture and plantar pressure. Depressive symptoms were also associated with foot pain at follow-up in those undergoing bariatric surgery, β = 1.2 (95% CI 0.8 to 1.7). Foot posture and hindfoot range of motion did not change following surgery and a change in plantar pressures was not associated with a change in foot pain. Conclusions Foot pain severity in bariatric surgery candidates was associated with depressive symptoms at baseline. Reduced foot pain following bariatric surgery was associated with an improvement in depressive symptoms, without a significant change in foot posture or foot function. Foot pain severity in bariatric candidates may be mediated by non-mechanical or non-local factors before and following surgery.TPW is currently supported by a Nursing and Allied Health Scholarship and Support Scheme funded by the Commonwealth Department of Health and administered by Services for Australian Rural and Remote Allied Health. JBA is currently supported by a National Health and Medical Research Council Early Career Research Fellowship (ID: 1120560). This study was funded by a Project Grant from Arthritis Australia

    Comparison of MODIS and SWAT evapotranspiration over a complex terrain at different spatial scales

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    © Author(s) 2018. This work is distributed under the Creative Commons Attribution 4.0 License.In most hydrological systems, evapotranspiration (ET) and precipitation are the largest components of the water balance, which are difficult to estimate, particularly over complex terrain. In recent decades, the advent of remotely sensed data based ET algorithms and distributed hydrological models has provided improved spatially upscaled ET estimates. However, information on the performance of these methods at various spatial scales is limited. This study compares the ET from the MODIS remotely sensed ET dataset (MOD16) with the ET estimates from a SWAT hydrological model on graduated spatial scales for the complex terrain of the Sixth Creek Catchment of the Western Mount Lofty Ranges, South Australia. ET from both models was further compared with the coarser-resolution AWRA-L model at catchment scale. The SWAT model analyses are performed on daily timescales with a 6-year calibration period (2000– 2005) and 7-year validation period (2007–2013). Differences in ET estimation between the SWAT and MOD16 methods of up to 31, 19, 15, 11 and 9% were observed at respectively 1, 4, 9, 16 and 25 km2 spatial resolutions. Based on the results of the study, a spatial scale of confidence of 4 km2 for catchment-scale evapotranspiration is suggested in complex terrain. Land cover differences, HRU parameterisation in AWRA-L and catchment-scale averaging of input climate data in the SWAT semi-distributed model were identified as the principal sources of weaker correlations at higher spatial resolution

    Probing the correlation between insulin activity and structural stability through introduction of the rigid A6–A11 bond

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    This research was originally published in the Journal of Biological Chemistry. Ong, S. C., Belgi, A., van Lierop, B., Delaine, C., Andrikopoulos, S., MacRaild, C. A., … Forbes, B. E. Probing the correlation between insulin activity and structural stability through introduction of the rigid A6–A11 bond. J. Biol. Chem. 2018; V293, 11928-11943. © the Author(s). which has been published in final form at https://doi.org/10.1074/jbc.RA118.002486The development of fast-acting and highly stable insulin analogues is challenging. Insulin undergoes structural transitions essential for binding and activation of the insulin receptor (IR), but these conformational changes can also affect insulin stability. Previously, we substituted the insulin A6–A11 cystine with a rigid, non-reducible C=C linkage (“dicarba” linkage). A cis-alkene permitted the conformational flexibility of the A-chain N-terminal helix necessary for high-affinity IR binding, resulting in surprisingly rapid activity in vivo. Here, we show that, unlike the rapidly acting LysB28ProB29 insulin analogue (KP insulin), cis-dicarba insulin is not inherently monomeric. We also show that cis-dicarba KP insulin lowers blood glucose levels even more rapidly than KP insulin, suggesting that an inability to oligomerize is not responsible for the observed rapid activity onset of cis-dicarba analogues. Although rapid-acting, neither dicarba species is stable, as assessed by fibrillation and thermodynamics assays. MALDI analyses and molecular dynamics simulations of cis-dicarba insulin revealed a previously unidentified role of the A6–A11 linkage in insulin conformational dynamics. By controlling the conformational flexibility of the insulin B-chain helix, this linkage affects overall insulin structural stability. This effect is independent of its regulation of the A-chain N-terminal helix flexibility necessary for IR engagement. We conclude that high-affinity IR binding, rapid in vivo activity, and insulin stability can be regulated by the specific conformational arrangement of the A6–A11 linkage. This detailed understanding of insulin's structural dynamics may aid in the future design of rapid-acting insulin analogues with improved stability.SCO and BVL acknowledge the financial support from the Australian postgraduate scholarships. RSN acknowledges fellowship support from the Australian National Health and Medical Research Council. AJR and BEF acknowledge funding from the National Health and Medical Research Council (Project Grant APP1069328) and Australian Research Council (LP12020200792)

    Neutrophil to lymphocyte ratio and clinical outcomes in COPD: recent evidence and future perspectives

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    ERR articles are open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.Chronic obstructive pulmonary disease (COPD) is a disabling condition that is characterised by poorly reversible airflow limitation and inflammation. Acute exacerbations of COPD are a common cause of hospitalisation and death among COPD patients. Several biochemical markers have been studied as outcome predictors in COPD; however, their measurement often requires significant time and resources. Relatively simple biomarkers of inflammation calculated from routine complete blood count tests, such as the neutrophil to lymphocyte ratio (NLR), might also predict COPD progression and outcomes. This review discusses the available evidence from studies investigating the associations between the NLR, COPD exacerbations and death in this patient group

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