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BACKGROUND Following total knee arthroplasty (TKA), 10-20% of patients report being dissatisfied with procedure outcomes. There is growing recognition that post-surgical satisfaction is shaped not only by the quality of surgery, but also by psychological and social factors. Surprisingly, information on psychological and social determinants of surgical outcome is rarely collected pre-surgery. Comprehensive collection of biopsychosocial information could assist clinicians when making recommendations in relation to rehabilitation, particularly if there was robust evidence to support the ability of pre-surgical constructs to predict post-surgical outcomes. Clinical decision support tools can help to identify factors influencing patient outcomes and support the provision of interventions or services which can be tailored to meet individuals’ needs. However, despite their potential clinical benefit, the application of such tools remains limited. OBJECTIVE This project is designed to develop a clinical decision tool that will assist with patient stratification and more precisely targeted clinical decision-making regarding pre-habilitation and rehabilitation for TKA, based on identified individual biopsychosocial needs. METHODS In this prospective, observational study, all participants provided written or electronic consent prior to study commencement. Patient-completed questionnaires captured information relating to a broad range of biopsychosocial parameters during the month preceding TKA. This included demographic factors (sex, age, rurality) psychological factors (mood status, pain catastrophizing, resilience and committed action), quality of life, social supports, lifestyle factors and knee symptoms. Physical measures assessing mobility, balance, and functional lower body strength were undertaken via videocalls with patients in their home. Information relating to pre-existing health issues and concomitant medications was derived from hospital medical records. Patient recovery outcomes were assessed three months following the surgical procedure and included quality of life, patient-reported knee symptoms, satisfaction with the surgical procedure and mood status. RESULTS This study was funded in September 2018 by the Ramsay Hospital Research Foundation. Patient recruitment and data collection commenced in November 2019 and completed in June 2022. A total of 1050 TKA patients were enrolled to take part in this study. Machine learning data analysis techniques will be applied to determine which pre-surgery parameters have the strongest power for predicting patient recovery following total knee replacement. From these analyses a predictive model will be developed. Predictive models will undergo internal validation, and Bayesian analysis will be applied to provide additional metrics regarding prediction accuracy. CONCLUSIONS Our findings will facilitate the development of the first comprehensive biopsychosocial prediction tool, which has the potential to objectively predict a patient’s individual recovery outcomes following TKA once selected by an orthopaedic surgeon to undergo TKA. If successful, the tool could also inform the evolution rehabilitation services, such that factors in addition to physical performance can be addressed and have the potential to further enhance patient recovery and satisfaction. CLINICALTRIAL Australian New Zealand Clinical Trials Registry ANZCTR 12619001000190; https://www.anzctr.org.au/ACTRN12619001000190.spx Universal Trials Number (UTN) U1111-1235-7747.

Background Research impact is an emerging measure of research achievement alongside traditional academic outputs such as publications. We present the results of applying the Framework to Assess the Impact from Translational health research (FAIT) to the Centre for Research Excellence (CRE) in Stroke Rehabilitation and Brain Recovery (CRE-Stroke, 2014–2019) and report on the feasibility and lessons from the application of FAIT to a CRE rather than a discrete research project. Methods Data were gathered via online surveys, in-depth interviews, document analysis and review of relevant websites/databases to report on the three major FAIT methods: the modified Payback Framework, an assessment of costs against monetized consequences, and a narrative account of the impact generated from CRE-Stroke activities. FAIT was applied during the last 4 years of CRE-Stroke operation. Results With an economic investment of AU$ 3.9 million over 5 years, CRE-Stroke delivered a return on investment that included AU$ 18.8 million in leveraged grants, fellowships and consultancies. Collectively, CRE-Stroke members produced 354 publications that were accessed 470,000 times and cited over 7220 times. CRE-Stroke supported 26 PhDs, 39 postdocs and seven novice clinician researchers. There were 59 capacity-building events benefiting 744 individuals including policy-makers and consumers. CRE-Stroke created research infrastructure (including a research register of stroke survivors and a brain biobank), and its global leadership produced international consensus recommendations to influence the stroke research landscape worldwide. Members contributed to the Australian Living Stroke Guidelines: four researchers’ outputs were directly referenced. Based only on the consequences that could be monetized, CRE-Stroke returned AU$ 4.82 for every dollar invested in the CRE. Conclusion This case example in the developing field of impact assessment illustrates how researchers can use evidence to demonstrate and report the impact of and returns on research investment. The prospective application of FAIT by a dedicated research impact team demonstrated impact in broad categories of knowledge-gain, capacity-building, new infrastructure, input to policy and economic benefits. The methods can be used by other research teams to provide comprehensive evidence to governments and other research funders about what has been generated from their research investment but requires dedicated resources to complete.

BACKGROUND Medical student burnout is a prevalent problem with adverse long-term outcomes. Incorporating psychological resource-building interventions into comprehensive burnout prevention approaches during medical training is an identified priority among educators. These interventions could reduce burnout risk by buffering students against nonmodifiable career stressors. However, there is a need for rigorous investigation into optimal intervention targets and methods. Psychological flexibility (PF) is an adaptive behavioral skill set that has demonstrated relationships with medical student burnout and well-being. More broadly, there is evidence that PF mediates burnout and well-being outcomes and may be a protective factor. Efficacy studies assessing the benefits of interventions targeting PF among medical students are needed. Research also supports the need to establish optimal methods for increasing intervention efficacy in the context of individual differences in burnout and PF by using individualized approaches. OBJECTIVE This study aims to assess whether an app-delivered PF intervention (Acceptance and Commitment Training) reduces burnout and improves well-being among medical students. We will examine whether changes in burnout and well-being are mediated by changes in PF. The potential benefits of an individualized version of the app versus those of a nonindividualized version will also be evaluated. METHODS In this 3-arm, parallel, randomized controlled study, a sample of medical students will be randomly allocated to 1 of 3 intervention arms (individualized, nonindividualized, and waiting list) by using a 1:1:1 allocation ratio. Participants in the individualized and nonindividualized intervention arms will have 8 weeks to access the app, which includes a PF concepts training session (stage 1) and access to short PF skill activities on demand (stage 2). Stage 2 will be either individualized to meet participants’ identified PF training needs at each log-in or nonindividualized. RESULTS Burnout, well-being, and PF will be assessed at baseline and after the intervention. Quantitative analyses will include descriptive and inferential statistics. We hypothesize that the Acceptance and Commitment Training intervention app will be effective in improving burnout and well-being and that changes in these outcomes will be mediated by changes in PF. We further hypothesize that participants in the individualized intervention group will demonstrate greater improvements in burnout and well-being outcomes than those in the nonindividualized group. CONCLUSIONS The findings of this study could guide the development of burnout prevention and well-being initiatives for medical students. Identifying PF as a mediating process would provide support for the delivery of preventive intervention programs that train individuals to strengthen this psychological resource before burnout symptoms emerge. This would be an important step in addressing and potentially offsetting the significant costs of burnout among medical students and physicians. Demonstrating the superiority of an individualized version of the app over a nonindividualized version would have implications for enhancing intervention precision and efficacy by using scalable interventions. CLINICALTRIAL ANZCTR 12621000911897

Background Stroke can be a life-changing event, with survivors frequently experiencing some level of disability, reduced independence, and an abrupt lifestyle change. Not surprisingly, many stroke survivors report elevated levels of stress during the recovery process, which has been associated with worse outcomes. Purpose Given the multiple roles of stress in the etiology of stroke recovery outcomes, we aimed to scope the existing literature on stress management interventions that have been trialed in stroke survivors. Methods We performed a database search for intervention studies conducted in stroke survivors which reported the effects on stress, resilience, or coping outcome. Medline (OVID), Embase (OVID), CINAHL (EBSCO), Cochrane Library, and PsycInfo (OVID) were searched from database inception until March 11, 2019, and updated on September 1, 2020. Results Twenty-four studies met the inclusion criteria. There was significant variation in the range of trialed interventions, as well as the outcome measures used to assess stress. Overall, just over half (13/24) of the included studies reported a benefit in terms of stress reduction. Acceptability and feasibility were considered in 71% (17/24) and costs were considered in 17% (4/24) of studies. The management of stress was rarely linked to the prevention of symptoms of stress-related disorders. The overall evidence base of included studies is weak. However, an increase in the number of studies over time suggests a growing interest in this subject. Conclusions Further research is required to identify optimum stress management interventions in stroke survivors, including whether the management of stress can ameliorate the negative impacts of stress on health.

Modern work environments have extensive interactions with technology and greater cognitive complexity of the tasks, which results in human operators experiencing increased mental workload. Air traffic control operators routinely work in such complex environments, and we designed tracking and collision prediction tasks to emulate their elementary tasks. The physiological response to the workload variations in these tasks was elucidated to untangle the impact of workload variations experienced by operators. Electroencephalogram (EEG), eye activity, and heart rate variability (HRV) data were recorded from 24 participants performing tracking and collision prediction tasks with three levels of difficulty. Our findings indicate that variations in task load in both these tasks are sensitively reflected in EEG, eye activity and HRV data. Multiple regression results also show that operators' performance in both tasks can be predicted using the corresponding EEG, eye activity and HRV data. The results also demonstrate that the brain dynamics during each of these tasks can be estimated from the corresponding eye activity, HRV and performance data. Furthermore, the markedly distinct neurometrics of workload variations in the tracking and collision prediction tasks indicate that neurometrics can provide insights on the type of mental workload. These findings have applicability to the design of future mental workload adaptive systems that integrate neurometrics in deciding not just "when" but also "what" to adapt. Our study provides compelling evidence in the viability of developing intelligent closed-loop mental workload adaptive systems that ensure efficiency and safety in complex work environments.

Background Physician burnout is a common problem, with onset frequently occurring during undergraduate education. Early intervention strategies that train medical students in psychological flexibility skills could support well-being and mitigate burnout risks associated with unmodifiable career stressors. There is a need for randomized controlled trials to assess effectiveness. As psychological flexibility varies contextually and among individuals, tailoring interventions may improve outcomes. Smartphone apps can facilitate individualization and accessibility, and the evaluation of this approach is an identified research priority. Objective This study aimed to evaluate the effectiveness of a stand-alone app–delivered Acceptance and Commitment Training intervention for improving medical students’ self-reported burnout, well-being, psychological flexibility, and psychological distress outcomes. We aimed to explore whether an individualized app would demonstrate benefits over a nonindividualized version. Methods This parallel randomized controlled trial was conducted with a sample of medical students from 2 Australian universities (N=143). Participants were randomly allocated to 1 of 3 intervention arms (individualized, nonindividualized, and waitlist) using a 1:1:1 allocation ratio. Individualized and nonindividualized participants were blinded to group allocation. The 5-week intervention included an introductory module (stage 1) and on-demand access to short skill training activities (stage 2), which students accessed at their own pace. Stage 2 was either nonindividualized or individualized to meet students’ identified psychological flexibility training needs. Results The mean differences in change from baseline between the intervention groups and the waitlist group were not statistically significant for burnout outcomes: exhaustion (primary; individualized: −0.52, 95% CI −3.70 to 2.65, P=.75; nonindividualized: 1.60, 95% CI −1.84 to 5.03, P=.37), cynicism (individualized: −1.26, 95% CI −4.46 to 1.94, P=.44; nonindividualized: 1.00, 95% CI −2.45 to 4.46, P=.57), and academic efficacy (individualized: 0.94, 95% CI −0.90 to 2.79, P=.32; nonindividualized: 2.02, 95% CI 0.02-4.03, P=.05). Following the intervention, the individualized group demonstrated improved psychological flexibility (0.50, 95% CI 0.12-0.89; P=.01), reduced inflexibility (0.48, 95% CI −0.92 to −0.04; P=.04), and reduced stress (−6.89, 95% CI −12.01 to 5.99; P=.01), and the nonindividualized group demonstrated improved well-being (6.46, 95% CI 0.49-12.42; P=.04) and stress (−6.36, 95% CI −11.90 to −0.83; P=.03) compared with waitlist participants. Between-group differences for the individualized and nonindividualized arms were not statistically significant. High attrition (75/143, 52.4%) was observed. Conclusions This trial provides early support for the potential benefits of Acceptance and Commitment Training for medical student well-being and psychological outcomes and demonstrates that psychological flexibility and inflexibility can be trained using a smartphone app. Although postintervention burnout outcomes were not statistically significant, improvements in secondary outcomes could indicate early risk mitigation. Replication studies with larger samples and longer-term follow-up are required, and future research should focus on improving implementation frameworks to increase engagement and optimize individualization methods. Trial Registration Australian New Zealand Clinical Trials Registry 12621000911897; https://tinyurl.com/2p92cwrw International Registered Report Identifier (IRRID) RR2-10.2196/32992

Background Medical students are at higher risk of burnout than the general population. Interventions that facilitate adaptive coping behaviors (eg, Psychological Flexibility) in the context of inherent stressors associated with medical training could mitigate burnout risk and improve well-being. Delivering these interventions using smartphone apps offers advantages such as accessibility, scalability, mitigation of time and stigma barriers, and facilitation of individual tailoring (individualization). There is a need for feasibility trials with medical students in this emerging field. Formal evaluations of user experiences of app-based psychological skill training are required to identify barriers to and facilitators of engagement and optimize intervention development before implementation in efficacy trials and real-world settings. Objective This study aimed to assess the feasibility of delivering an individualized Psychological Flexibility skill training intervention (Acceptance and Commitment Training [ACTraining]) to medical students using an app-based delivery format. We further aimed to explore how formal evaluation of user experiences might inform and guide the development of this app before implementation in an efficacy trial and future research involving app-delivered psychological skill training for medical students. Methods This single-arm study was an early-phase feasibility trial of a stand-alone ACTraining app conducted with a sample of Australian medical students (n=11). We collected app usability and user experience data across a broad range of domains (eg, perceived helpfulness and relevance, learning experiences, and self-efficacy) using self-report questionnaires (quantitative and qualitative) and behavioral engagement outcomes. Results Behavioral engagement data demonstrated that the app delivered the assessment procedures and individualized ACTraining intervention to medical students as intended. The subjective feedback provided by students who actively engaged with the app was generally positive across several indicators, including usability, perceived relevance and helpfulness, accessibility, maintenance of privacy, and opportunity for self-reflection. Disengagement from the app was an identified challenge throughout the trial. Participant feedback identified several factors that may have affected engagement, such as time, expectations regarding app interface functioning, and individual differences in confidence and self-efficacy when implementing skills. Conclusions This study reports user experience data that have been largely absent from the literature on digital psychological interventions for medical students. Our findings demonstrate the preliminary feasibility of an app-delivered ACTraining intervention for medical student well-being and burnout and support the value of future assessment of the efficacy of this approach with larger samples. We consider subjective feedback from medical students in relation to observed engagement and propose how this information might be used to inform the development of this app and future research in this nascent field.

BACKGROUND Medical student burnout is a prevalent problem with adverse long-term outcomes. Incorporating psychological resource-building interventions into comprehensive burnout prevention approaches during medical training is an identified priority among educators. These interventions could reduce burnout risk by buffering students against nonmodifiable career stressors. However, there is a need for rigorous investigation into optimal intervention targets and methods. Psychological flexibility (PF) is an adaptive behavioral skill set that has demonstrated relationships with medical student burnout and well-being. More broadly, there is evidence that PF mediates burnout and well-being outcomes and may be a protective factor. Efficacy studies assessing the benefits of interventions targeting PF among medical students are needed. Research also supports the need to establish optimal methods for increasing intervention efficacy in the context of individual differences in burnout and PF by using individualized approaches. OBJECTIVE This study aims to assess whether an app-delivered PF intervention (Acceptance and Commitment Training) reduces burnout and improves well-being among medical students. We will examine whether changes in burnout and well-being are mediated by changes in PF. The potential benefits of an individualized version of the app versus those of a nonindividualized version will also be evaluated. METHODS In this 3-arm, parallel, randomized controlled study, a sample of medical students will be randomly allocated to 1 of 3 intervention arms (individualized, nonindividualized, and waiting list) by using a 1:1:1 allocation ratio. Participants in the individualized and nonindividualized intervention arms will have 5 weeks to access the app, which includes a PF concepts training session (stage 1) and access to short PF skill activities on demand (stage 2). Stage 2 will be either individualized to meet participants’ identified PF training needs at each log-in or nonindividualized. RESULTS Burnout, well-being, and PF will be assessed at baseline and after the intervention. Quantitative analyses will include descriptive and inferential statistics. We hypothesize that the Acceptance and Commitment Training intervention app will be effective in improving burnout and well-being and that changes in these outcomes will be mediated by changes in PF. We further hypothesize that participants in the individualized intervention group will demonstrate greater improvements in burnout and well-being outcomes than those in the nonindividualized group. CONCLUSIONS The findings of this study could guide the development of burnout prevention and well-being initiatives for medical students. Identifying PF as a mediating process would provide support for the delivery of preventive intervention programs that train individuals to strengthen this psychological resource before burnout symptoms emerge. This would be an important step in addressing and potentially offsetting the significant costs of burnout among medical students and physicians. Demonstrating the superiority of an individualized version of the app over a nonindividualized version would have implications for enhancing intervention precision and efficacy by using scalable interventions. CLINICALTRIAL Australian New Zealand Clinical Trials Registry ANZCTR 12621000911897; https://www.anzctr.org.au/ACTRN12621000911897.aspx INTERNATIONAL REGISTERED REPORT PRR1-10.2196/32992

Autism Spectrum Disorder (ASD; autism) is a neurodevelopmental disorder characterised by deficits in social communication, and restricted and/or repetitive behaviours. While the precise pathophysiologies are unclear, increasing evidence supports a role for dysregulated neuroinflammation in the brain with potential effects on synapse function. Here, we studied characteristics of microglia and astrocytes in the Neuroligin-3 (NL3R451C) mouse model of autism since these cell types are involved in regulating both immune and synapse function. We observed increased microglial density in the dentate gyrus (DG) of NL3R451C mice without morphological differences. In contrast, WT and NL3R451C mice had similar astrocyte density but astrocyte branch length, the number of branch points, as well as cell radius and area were reduced in the DG of NL3R451C mice. Because retraction of astrocytic processes has been linked to altered synaptic transmission and dendrite formation, we assessed for regional changes in pre- and postsynaptic protein expression in the cortex, striatum and cerebellum in NL3R451C mice. NL3R451C mice showed increased striatal postsynaptic density 95 (PSD-95) protein levels and decreased cortical expression of synaptosomal-associated protein 25 (SNAP-25). These changes could contribute to dysregulated neurotransmission and cognition deficits previously reported in these mice.

Objectives People with stroke sit for long periods each day, which may compromise blood glucose control and increase risk of recurrent stroke. Studies in other populations have found regular activity breaks have a significant immediate (within-day) positive effect on glucose metabolism. We examined the effects of breaking up uninterrupted sitting with frequent, short bouts of light-intensity physical activity in people with stroke on post-prandial plasma glucose and insulin. Methods Randomized within-participant crossover trial. We included people between 3 months and 10 years post-stroke, ambulant with minimal assistance and not taking diabetic medication other than metformin. The three experimental conditions (completed in random order) were: sitting for 8 h uninterrupted, sitting with 3 min bouts of light-intensity exercise while standing every 30 min, or sitting with 3 min of walking every 30 min. Meals were standardized and bloods were collected half- to one-hourly via an intravenous cannula. Results A total of 19 participants (9 female, mean [SD] age 68.2 [10.2]) completed the trial. The majority ( n = 12, 63%) had mild stroke symptoms (National Institutes of Stroke Scale score 0–13). There was no significant effect of experimental condition on glucose (mean [SD] positive incremental area [+iAUC] mmol·L·h-1 under the curve during sitting 42.3 [29.5], standing 47.4 [23.1], walking 44.6 [26.5], p = 0.563) or insulin (mean + iAUC pmol·L·h-1 sitting 14,161 [7,560], standing 14,043 [8,312], walking 14,008 [8,269], p = 0.987). Conclusion Frequent, short bouts of light-intensity physical activity did not have a significant effect on post-prandial plasma glucose and insulin in this sample of people with stroke. Further studies are needed to identify strategies that improve inactivity-related glucose metabolism after stroke.

Background Medical student burnout is a prevalent problem with adverse long-term outcomes. Incorporating psychological resource-building interventions into comprehensive burnout prevention approaches during medical training is an identified priority among educators. These interventions could reduce burnout risk by buffering students against nonmodifiable career stressors. However, there is a need for rigorous investigation into optimal intervention targets and methods. Psychological flexibility (PF) is an adaptive behavioral skill set that has demonstrated relationships with medical student burnout and well-being. More broadly, there is evidence that PF mediates burnout and well-being outcomes and may be a protective factor. Efficacy studies assessing the benefits of interventions targeting PF among medical students are needed. Research also supports the need to establish optimal methods for increasing intervention efficacy in the context of individual differences in burnout and PF by using individualized approaches. Objective This study aims to assess whether an app-delivered PF intervention (Acceptance and Commitment Training) reduces burnout and improves well-being among medical students. We will examine whether changes in burnout and well-being are mediated by changes in PF. The potential benefits of an individualized version of the app versus those of a nonindividualized version will also be evaluated. Methods In this 3-arm, parallel, randomized controlled study, a sample of medical students will be randomly allocated to 1 of 3 intervention arms (individualized, nonindividualized, and waiting list) by using a 1:1:1 allocation ratio. Participants in the individualized and nonindividualized intervention arms will have 5 weeks to access the app, which includes a PF concepts training session (stage 1) and access to short PF skill activities on demand (stage 2). Stage 2 will be either individualized to meet participants’ identified PF training needs at each log-in or nonindividualized. Results Burnout, well-being, and PF will be assessed at baseline and after the intervention. Quantitative analyses will include descriptive and inferential statistics. We hypothesize that the Acceptance and Commitment Training intervention app will be effective in improving burnout and well-being and that changes in these outcomes will be mediated by changes in PF. We further hypothesize that participants in the individualized intervention group will demonstrate greater improvements in burnout and well-being outcomes than those in the nonindividualized group. Conclusions The findings of this study could guide the development of burnout prevention and well-being initiatives for medical students. Identifying PF as a mediating process would provide support for the delivery of preventive intervention programs that train individuals to strengthen this psychological resource before burnout symptoms emerge. This would be an important step in addressing and potentially offsetting the significant costs of burnout among medical students and physicians. Demonstrating the superiority of an individualized version of the app over a nonindividualized version would have implications for enhancing intervention precision and efficacy by using scalable interventions. Trial Registration Australian New Zealand Clinical Trials Registry ANZCTR 12621000911897; https://www.anzctr.org.au/ACTRN12621000911897.aspx International Registered Report Identifier (IRRID) PRR1-10.2196/32992

Traumatic brain injury results in devastating long-term functional damage due to the growth inhibition of the inflammatory response, and in particular, the complex response of astrocytes. Sustained, nonsteroidal anti-inflammatory approaches that can attenuate this response are of interest to improve therapeutic outcomes, particularly when combined with a tissue engineering construct that recapitulates the physiological microenvironment to facilitate functional repair. Here, we present a multifaceted, therapeutic extracellular-matrix mimic consisting of a coassembled scaffold with a laminin-inspired self-assembling peptide hydrogel, Fmoc-DIKVAV, and the anti-inflammatory macromolecule, fucoidan. At 7 days post-injury, our novel multicomponent hydrogel system presenting biologically relevant nanofibers and the anti-inflammatory fucoidan attenuated the primary glial scar to half that of a stab (control) injury. Further, the presentation of fucoidan increased the organization of astrocytes within the glial scar, while also significantly changing the morphology of astrocytes distal from the administered hydrogel and further into the parenchyma. This demonstrates that the anti-inflammatory fucoidan, present on the surface of the Fmoc-DIKVAV nanofibers, causes a change in astrocyte phenotype post-injury attenuating "reactive" astrocytosis. For the first time, we present a multicomponent tissue engineering construct to promote a growth-permissive environment

Total knee arthroplasty (TKA) is a commonly implemented elective surgical treatment for end-stage osteoarthritis of the knee, demonstrating high success rates when assessed by objective medical outcomes. However, a considerable proportion of TKA patients report significant dissatisfaction postoperatively, related to enduring pain, functional limitations, and diminished quality of life. In this conceptual analysis, we highlight the importance of assessing patient-centered outcomes routinely in clinical practice, as these measures provide important information regarding whether surgery and postoperative rehabilitation interventions have effectively remediated patients’ real-world “quality of life” experiences. We propose a novel precision medicine approach to improving patient-centered TKA outcomes through the development of a multivariate machine-learning model. The primary aim of this model is to predict individual postoperative recovery trajectories. Uniquely, this model will be developed using an interdisciplinary methodology involving non-linear analysis of the unique contributions of a range of preoperative risk and resilience factors to patient-centered TKA outcomes. Of particular importance to the model’s predictive power is the inclusion of a comprehensive assessment of modifiable psychological risk and resilience factors that have demonstrated relationships with TKA and other conditions in some studies. Despite the potential for patient psychological factors to limit recovery, they are typically not routinely assessed preoperatively in this patient group, and thus can be overlooked in rehabilitative referral and intervention decision-making. This represents a research-to-practice gap that may contribute to adverse patient-centered outcomes. Incorporating psychological risk and resilience factors into a multivariate prediction model could improve the detection of patients at risk of sub-optimal outcomes following TKA. This could provide surgeons and rehabilitation providers with a simplified tool to inform postoperative referral and intervention decision-making related to a range of interdisciplinary domains outside their usual purview. The proposed approach could facilitate the development and provision of more targeted rehabilitative interventions on the basis of identified individual needs. The roles of several modifiable psychological risk and resilience factors in recovery are summarized, and intervention options are briefly presented. While focusing on rehabilitation following TKA, we advocate for the broader utilization of multivariate prediction models to inform individually tailored interventions targeting a range of health conditions. Published version

Background: The unanticipated devastating changes affecting the quality of life post-stroke leads to chronic stress. Elevated stress has been associated with the several worst outcomes of stroke. However, not all stroke survivors with acute stress advances to the stage of severe unfavourable outcomes. Apart from stroke severity, the functional outcome of stroke is embedded within the complex settings of individual’s unique personality traits such as resiliency. In this ongoing project, we aim to explore the relationship between resiliency and stress in stroke survivors and more importantly, we aim to investigate how they influence the recovery trajectory of stroke survivors. Methods: Community dwelling stroke survivors were recruited from Hunter Stroke Research Register. Demographics data, anthropometrics data and medical history related to cardiometabolic diseases were recorded. Stroke recovery was assessed from Stroke Impact Scale -version 3. Self-reported resilience was assessed using the Brief Resiliency Scale and Connor Davidson Resilience Scale. The level of stress was assessed using Perceived Stress Scale-10. Data were analysed using IBM SPSS Statistics. Results: All of the recruited stroke survivors (N=45; age: 62.6±13.49; male/female: 25/20; ischaemic/haemorrhagic: 29/16) were at the chronic phase of their stroke recovery. The strong inverse association was found between the level of resilience and the level of stress. Resiliency level correlated significantly with 6 out of 8 domains of stroke impact scale. There was no correlation between the level of stress and resiliency with demographics, anthropometric variables and associated cardiometabolic conditions. In stepwise multiple regression analysis, resiliency level was significantly associated with several domains of stroke impact scale and it accounted for the significant proportion of variance in stroke recovery. Conclusion: Since, resilience was inversely associated with stress level and higher resilience level was associated with favourable stroke recovery trajectory; equipping stroke survivor’s skills in building and maintaining resilience will reduce the level of stress and promote recovery at chronic phase post-stroke.

Introduction: The incidence of pituitary dysfunction after severe ischemic stroke is unknown, however given the increasing attention to pituitary dysfunction after neurological injuries such as traumatic brain injury, this may represent a novel area of research in stroke. Methods: We perform an arginine and human growth hormone releasing hormone challenge on ischemic stroke patients within a week of symptom onset. Results: Over the study period, 13 patients were successfully tested within a week of stroke (baseline NIHSS 10, range 7-16). Overall, 9(69%) patients had a poor response, with 7(54%) of these patients meeting the criteria for had human growth hormone deficiency. Other measures of pituitary function were within normal ranges. Conclusion: After major ischemic stroke, low GH levels are common and may play a role in stroke recovery.

Cerebral ischemia results in damage to neuronal circuits and lasting impairment in function. We have previously reported that stimulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors with the ampakine, CX1837, increases brain-derived neurotrophic factor (BDNF) levels and affords significant motor recovery after stroke in young mice. Here, we investigated whether administration of CX1837 in aged (24 months old) mice was equally effective. In a model of focal ischemia, administration of CX1837 from 5 days after stroke resulted in a small gain of motor function by week 6 after stroke. Mice that received a local delivery of BDNF via hydrogel implanted into the stroke cavity also showed a small gain of function from 4 to 6 weeks after stroke. Combining both treatments, however, resulted in a marked improvement in motor function from 2 weeks after insult. Assessment of peri-infarct tissue 2 weeks after stroke revealed a significant increase in p-AKT and p-CREB after the combined drug treatment. Using the pan-AKT inhibitor, GSK-690693, or deletion of CREB from forebrain neurons using the CREB-flox/CAMKii-cre mice, we were able to block the recovery of motor function. These data suggest that combined CX1837 and local delivery of BDNF are required to achieve maximal functional recovery after stroke in aged mice, and is occurring via the AKT-GSK3-CREB signaling pathway.

Within the last decade, there has been significant change in the way tertiary midwifery education has been delivered to students. The use of blended teaching methods and the introduction of simulated learning experiences has been observed in the literature to improve students' self-confidence, competence, clinical judgement and decision-making abilities. Simulation is seen to be particularly important when practising skills that may be infrequently encountered in practice, such as clinical emergencies. Neonatal resuscitation is the most common neonatal emergency encountered within midwifery today, with up to 15% of babies requiring some form of resuscitation at birth. Recent research describes the benefits of using a multi-modal approach to teaching neonatal resuscitation, utilising both theory and simulated learning methods. One emerging method of simulation is that of virtual reality (VR), which has been recognised for its enormous educational potential in risk-free clinical skills training. Currently, however, there is limited research looking at the use of VR in emergency skills training. This article examines the literature to highlight the potential benefits that VR simulation could provide for emergency skills training, as well as the potential challenges that should be acknowledged.

Excessive sitting is detrimentally associated with cardiovascular disease and all-cause mortality. Frequent breaks in prolonged sitting can improve cardiometabolic responses in non-stroke populations. However, this has not been established in stroke survivors. This study will determine the most effective dose of activity breaks that (i) produce clinically meaningful improvements in mean systolic blood pressure (primary outcome), postprandial glucose, and insulin responses (secondary outcomes), and (ii) is safe and feasible. We hypothesis that systolic blood pressure, postprandial insulin, and glucose responses will improve with increasing doses of activity and be most effective at the maximum safe and feasible dose of activity. Thirty participants in the most effective dose will provide 80% power to detect a within-person, between-condition, difference of 3.5 mmHg in systolic blood pressure assuming a SD of 15 mmHg, within-person correlation of 0.9, and α = 0.05. Stroke survivors will complete 3 experimental conditions in a within-participant, dose escalation design including (i) uninterrupted sitting (8 h), (ii) Dose 1: uninterrupted sitting with bouts of light-intensity exercises while standing (initial dose involves two 5-min breaks), and (iii) Dose 2: two additional 5-min breaks above Dose 1. Ambulatory blood pressure will be collected every 30 min during experimental conditions and hourly for 24-h post-experimental conditions. Blood samples will be collected every 30 min during 2-h postprandial periods. This study will identify the most effective dose of light-intensity exercises while standing to improve cardiometabolic responses in stroke survivors.

Exposure to social stress has been linked to the development and maintenance of mood-related psychopathology; however, the underlying neurobiological changes remain uncertain. In this study, we examined numbers of DFosB-immunoreactive cells in the forebrains of rats subjected to 12 episodes of social defeat. This was achieved using the social conflict model whereby animals are introduced into the home cage of older males (‘‘residents’’) trained to attack and defeat all such ‘‘intruders’’; importantly, controls were treated identically except that the resident was absent. Our results indicated that the only region in which DFosB-positive cells were found in significantly higher numbers in intruders than in controls was the infralimbic medial prefrontal cortex (mPFC). This same effect was not apparent using another psychological stressor, noise stress. Cells of the infralimbic mPFC also displayed evidence of chromatin remodeling. We found that exposure to repeated episodes of social defeat increased numbers of cells immunoreactive for histone H3 acetylation, but not for histone H3 phosphoacetylation, in the infralimbic mPFC. Collectively, these findings highlight the importance of the infralimbic mPFC in responding to social stress—a finding that provides insight into the possible neurobiological alterations associated with stress-induced psychiatric illness.

This article provides a brief commentary on Pfaff et al's timely review of the relations between mechanisms of CNS arousal and mechanisms of stress. Pfaff and colleagues use the review as a platform to propose the existence of a coherent stress-arousal state. We suggest that this proposal is, on a number of grounds, flawed. In turn, we counter that the while the states of stress and arousal are related they are as entities fundamentally separate. Moreover, we propose that any productive attempt to unite the two states must acknowledge the importance of and therefore centrally include higher order integrative phenomena, such as, appraisal.

Microglia are unique cells within the central nervous system because of their biophysical independence. As a result of this unusual property the cells must undergo significant structural remodelling in order to engage and connect with other elements within the central nervous system. Efficient remodelling is required for all activities that microglia are involved in ranging from monitoring synaptic information flow through to phagocytosis of tissue debris. Despite the fact that morphological remodelling is a pre-requisite to all microglial activities, relatively little research has been undertaken on the topic. This review examines what is known about how microglia transform themselves during development, under physiological conditions in response to changes in neuronal activity, and under pathological circumstances. Specific attention is given to exploring a variety of models that have been proposed to account for microglial transformation as well as the signals that are known to trigger these transformations.

Depression is a leading contributor to the global burden of diseases. Despite advances in research, challenges still exist in managing this disorder. Sufferers of autoimmune diseases are often observed to suffer from depression more often than healthy individuals, an association that cannot be completely accounted for by the impact of the disease on the individual. An association between autoimmunity and depressive symptoms also appears to exist in populations with subclinical symptoms. Moreover, researchers have successfully developed murine models illustrating the ability of autoantibodies to induce depressive-like symptoms. This paper will provide an overview of the association between autoantibodies and occurrence of depressive symptoms. Though current evidence appears to support a role for autoantibodies in the pathogenesis of depression, the majority of studies have examined this relationship cross-sectionally, therefore failing to establish a temporal association. Nonetheless, this novel theory meshes with older and newer neurochemical theories of depression. A better understanding of the immuno-pathogenesis underlying depression presents opportunities for more targeted treatment approaches and more timely and appropriate measures of detection.

Publisher Summary Emotions serve to facilitate decision making, and to organize and to motivate behavior. The advent of new techniques for investigating the structure and function of the brain, particularly the introduction of neuroimaging tools that allows one to study localized brain function during prescribed tasks, has led to a rapid improvement in the understanding of the neural substrates of emotional processing. The systems that have been put forward for describing emotions can be thought of as falling into two groups: categorical and dimensional. From a neurobiological perspective, the significance of these alternative approaches rests in the different ways in which they relate to associated theories concerning the neural underpinnings of emotion. Categorical systems are more numerous than dimensional systems and assume that there are a certain number of discrete, “basic” emotions; other emotions, if recognized, are seen as reflecting either differing levels of intensity. An alternative to a categorical system for describing emotions is a dimensional system. Although the categorical and dimensional systems are often characterized as constituting almostmutually exclusive alternatives, they can in some instances be regarded as complementary. Shifts in emotional state can be triggered by external or internal stimuli, with the latter category including thoughts, memories, or even one's conscious awareness of feelings generated by an antecedent emotion. Emotional appraisal can occur consciously or unconsciously, and studies on both human and non-human animals have provided strong evidence of a critical role for the amygdala in this process.

Abstract In the past innumerable pipelines, both onshore and offshore, have been replaced by a variety of methods. These have ranged from replacement of the pipeline to a sliplining of it by different means. These methods have different advantages and disadvantages due to the circumstances in which it is implemented. Several have environmental drawbacks and others suffer as a result of the large amount of equipment and personnel required to perform them. In order to minimize the time required to install a replacement gas pipeline SWEPI investigated the possibility of using coil tubing for this application. Upon presenting the scenario to Schlumberger Dowell the project left the realm of conjecture and began to be viewed as a viable option. The project consisted of the installation of one 3.5" coil tubing slip liner and two communications cables in the existing 8" gas production pipeline from SWEPI's Platform Emmy to the onshore receiving area at SWEPI's Huntington Beach Production Unit, Huntington Beach, California. This paper details the operational and design considerations that were involved in the project and illustrates one of the methods that have caused coil tubing to be such an innovative and indeed integral segment of well servicing.