'Physical well-being is our top priority': Healthcare professionals' challenges in supporting psychosocial well-being in stroke services.

BACKGROUND: Following stroke, a sense of well-being is critical for quality of life. However, people living with stroke, and health professionals, suggest that well-being is not sufficiently addressed within stroke services, contributing to persistent unmet needs. Knowing that systems and structures shape clinical practice, this study sought to understand how health professionals address well-being, and to examine how the practice context influences care practice. METHODS: Underpinned by Interpretive Description methodology, we interviewed 28 health professionals across multiple disciplines working in stroke services (acute and rehabilitation) throughout New Zealand. Data were analysed using applied tension analysis. RESULTS: Health professionals are managing multiple lines of work in stroke care: biomedical work of investigation, intervention and prevention; clinical work of assessment, monitoring and treatment; and moving people through service. While participants reported working to support well-being, this could be deprioritised amidst the time-oriented pressures of the other lines of work that were privileged within services, rendering it unsupported and invisible. CONCLUSION: Stroke care is shaped by biomedical and organisational imperatives that privilege physical recovery and patient throughput. Health professionals are not provided with the knowledge, skills, time or culture of care that enable them to privilege well-being within their work. This has implications for the well-being of people with stroke, and the well-being of health professionals. In making these discourses and culture visible, and tracing how these impact on clinical practice, we hope to provide insight into why well-being work remains other to the 'core' work of stroke, and what needs to be considered if stroke services are to better support people's well-being. PATIENT OR PUBLIC CONTRIBUTIONS: People with stroke, family members and people who provide support to people with stroke, and health professionals set priorities for this research. They advised on study conduct and have provided feedback on wider findings from the research.

Intrinsic motivation.

The prevailing wisdom in neurological rehabilitation, and particularly for stroke, is that physical therapies are the key to improvements in function. Despite accepting the importance of 'the motivated patient', the lack of simple, proven ways to improve intrinsic motivation has hindered efforts to combine physical therapies with motivation. Now there is available a simple, free, well-validated approach to encourage intrinsic motivation ('Take Charge'). The benefits for people who have had a stroke are well-established but this could be applied to people with a range of neurological and other disorders. We provide the evidential support for this approach and suggest ways of incorporating it into daily practice.

Outcomes and experiences of families with children with type 1 diabetes on insulin pumps through subsidised pump access programs in Western Australia.

Introduction: In Australia, access to insulin pump therapy for children with type 1 diabetes (T1D) is predominantly restricted to families with private health insurance. In an attempt to improve equity, additional subsidised pathways exist which provide pumps to families with reduced financial resources. We aimed to describe the outcomes and experiences of families with children commenced on pumps through these subsidised pathways in Western Australia (WA). Methods: Children with T1D in WA who did not have private health insurance and received pumps from the subsidised pump programs between January 2016 and December 2020 were included. Study 1 was designed to review glycaemic outcome. A retrospective analysis of HbA1c was conducted in the whole cohort and in children who commenced pump after the first year of diagnosis to exclude the impact of the partial clinical remission phase following diagnosis. HbA1c at baseline, and six, 12, 18 and 24 months after pump initiation were collected. Study 2 was designed to review experiences of families commenced on pumps through subsidised pathway. A questionnaire designed by the clinical team was distributed to parents via an online secure platform to capture their experiences. Results: Of the 61 children with mean (SD) age 9.0 (4.9) years who commenced pump therapy through subsidised pump programs, 34 children commenced pump therapy after one year of diagnosis of T1D. The median (IQR) HbA1c (%) in 34 children at baseline was 8.3 (1.3), with no statistically significant change from baseline at six months [7.9 (1.4)], 12 months [8.0 (1.5)], 18 months [8.0 (1.3)] or 24 months [8.0 (1.3)]. The questionnaire response rate was 56%. 83% reported intention to continue pump therapy, however 58% of these families did not have avenue to acquire private health insurance. Families expressed inability to procure private health insurance due to low income and unreliable employment and remained largely unsure about the pathway to obtain the next pump. Discussion: Children with T1D who commenced insulin pump therapy on subsidised pathways maintained glycaemic control for two years, and families favored pumps as a management option. However, financial limitations persist as a significant barrier to procure and continue pump therapy. Pathways for access need to be assessed and advocated.

SIRT3 deficiency decreases oxidative metabolism capacity but increases lifespan in male mice under caloric restriction.

Mitochondrial NAD+ -dependent protein deacetylase Sirtuin3 (SIRT3) has been proposed to mediate calorie restriction (CR)-dependent metabolic regulation and lifespan extension. Here, we investigated the role of SIRT3 in CR-mediated longevity, mitochondrial function, and aerobic fitness. We report that SIRT3 is required for whole-body aerobic capacity but is dispensable for CR-dependent lifespan extension. Under CR, loss of SIRT3 (Sirt3-/- ) yielded a longer overall and maximum lifespan as compared to Sirt3+/+ mice. This unexpected lifespan extension was associated with altered mitochondrial protein acetylation in oxidative metabolic pathways, reduced mitochondrial respiration, and reduced aerobic exercise capacity. Also, Sirt3-/- CR mice exhibit lower spontaneous activity and a trend favoring fatty acid oxidation during the postprandial period. This study shows the uncoupling of lifespan and healthspan parameters (aerobic fitness and spontaneous activity) and provides new insights into SIRT3 function in CR adaptation, fuel utilization, and aging.

Hippo pathway regulation by phosphatidylinositol transfer protein and phosphoinositides.

The Hippo pathway plays a key role in development, organ size control and tissue homeostasis, and its dysregulation contributes to cancer. The LATS tumor suppressor kinases phosphorylate and inhibit the YAP/TAZ transcriptional co-activators to suppress gene expression and cell growth. Through a screen of marine natural products, we identified microcolin B (MCB) as a Hippo activator that preferentially kills YAP-dependent cancer cells. Structure-activity optimization yielded more potent MCB analogs, which led to the identification of phosphatidylinositol transfer proteins α and ß (PITPα/ß) as the direct molecular targets. We established a critical role of PITPα/ß in regulating LATS and YAP. Moreover, we showed that PITPα/ß influence the Hippo pathway via plasma membrane phosphatidylinositol-4-phosphate. This study uncovers a previously unrecognized role of PITPα/ß in Hippo pathway regulation and as potential cancer therapeutic targets.

The Hippo pathway mediates Semaphorin signaling.

Semaphorins were originally identified as axonal guidance molecules, but they also control processes such as vascular development and tumorigenesis. The downstream signaling cascades of Semaphorins in these biological processes remain unclear. Here, we show that the class 3 Semaphorins (SEMA3s) activate the Hippo pathway to attenuate tissue growth, angiogenesis, and tumorigenesis. SEMA3B restoration in lung cancer cells with SEMA3B loss of heterozygosity suppresses cancer cell growth via activating the core Hippo kinases LATS1/2 (large tumor suppressor kinase 1/2). Furthermore, SEMA3 also acts through LATS1/2 to inhibit angiogenesis. We identified p190RhoGAPs as essential partners of the SEMA3A receptor PlexinA in Hippo regulation. Upon SEMA3 treatment, PlexinA interacts with the pseudo-guanosine triphosphatase (GTPase) domain of p190RhoGAP and simultaneously recruits RND GTPases to activate p190RhoGAP, which then stimulates LATS1/2. Disease-associated etiological factors, such as genetic lesions and oscillatory shear, diminish Hippo pathway regulation by SEMA3. Our study thus discovers a critical role of Hippo signaling in mediating SEMA3 physiological function.

Economic analysis of the 'Take Charge' intervention for people following stroke: Results from a randomised trial.

OBJECTIVE: To undertake an economic analysis of the Take Charge intervention as part of the Taking Charge after Stroke (TaCAS) study. DESIGN: An open, parallel-group, randomised trial comparing active and control interventions with blinded outcome assessment. SETTING: Community. PARTICIPANTS: Adults (n = 400) discharged to community, non-institutional living following acute stroke. INTERVENTIONS: The Take Charge intervention, a strengths based, self-directed rehabilitation intervention, in two doses (one or two sessions), and a control intervention (no Take Charge sessions). MEASURES: The cost per quality-adjusted life year (QALY) saved for the period between randomisation (always post hospital discharge) and 12 months following acute stroke. QALYs were calculated from the EuroQol-5D-5L. Costs of stroke-related and non-health care were obtained by questionnaire, hospital records and the New Zealand Ministry of Health. RESULTS: One-year post hospital discharge cost of care was mean (95% CI) $US4706 (3758-6014) for the Take Charge intervention group and $6118 (4350-8005) for control, mean (95% CI) difference $ -1412 (-3553 to +729). Health utility scores were mean (95% CI) 0.75 (0.73-0.77) for Take Charge and 0.71 (0.67-0.75) for control, mean (95% CI) difference 0.04 (0.0-0.08). Cost per QALY gained for the Take Charge intervention was $US -35,296 (=£ -25,524, € -30,019). Sensitivity analyses confirm Take Charge is cost-effective, even at a very low willingness-to-pay threshold. With a threshold of $US5000 per QALY, the probability that Take Charge is cost-effective is 99%. CONCLUSION: Take Charge is cost-effective and probably cost saving.

Planned Oocyte Cryopreservation: Outcomes, Motivations, and Involvement of Primary Health Care Providers.

Background: With improvements in oocyte cryopreservation and widespread delays in childbearing, planned oocyte cryopreservation (POC) has become an increasingly attractive option. This study aimed to (1) review POC cycle outcomes at an academic in vitro fertilization (IVF) center and (2) examine POC users' motivations for pursuing POC, fertility knowledge, and the involvement of their primary health care providers (PHP). Materials and Methods: POC cycle outcomes were collected from IVF records of the 224 women who underwent ≥1 cycle from 2012 to 2018. The 198 who were reachable by e-mail were invited to complete an online survey. The study was approved by the University of Toronto Research Ethics Board (No. 32951). Results: Mean age of the 224 women at first cycle was 36.4 (range: 25-42), with a significant decrease in anti-Müllerian hormone level (p = 0.001) and mean number of oocytes retrieved (p = 0.006) and cryopreserved per cycle (p = 0.042) with increasing age. From those invited for survey participation, 98 (49.5%) questionnaires were returned, with 86 evaluable. Majority of respondents were Caucasian (66%), single (93%), and earned a gross annual income of >$70,000 (74%). Strongest motivation for pursuing POC was concern about age-related fertility decline in the absence of a partner. Respondents' annual income was positively correlated with the number of completed cycles (p = 0.032). Half the respondents correctly identified age of onset of marked fertility decline as ≥35 years. In only 19% of cases was the conversation PHP initiated, and 29% never discussed POC with their PHP. Conclusions: More than 50% of women underwent POC at an age when fertility has begun to markedly decline. It is important for PHPs to identify and discuss POC with appropriate patients and offer accurate preliminary information and timely referrals for those interested in exploring this option.

Estimating the minimal clinically important difference for the Physical Component Summary of the Short Form 36 for patients with stroke.

OBJECTIVE: To determine the Physical Component Summary (PCS) score's minimal clinically important difference (MCID) on the Short Form 36 (SF-36) for people with stroke. METHODS: We conducted secondary analysis of data from a large randomized controlled trial (N = 400) in the post-hospital discharge phase of stroke rehabilitation with outcome measurement 6 and 12 months following stroke. Three methods were used for estimating the MCID: two anchor and one distribution. Method 1 compared SF-36 PCS scores at 12 months for responses to the SF-36's Perceived Health Change (PHC) question. Method 2 compared the change in PCS score between 6 and 12 months for responses to the PHC question. Method 3 used Cohen's method to estimate the MCID from the PCS score distribution. RESULTS: Method 1: the mean PCS score increased by 3.0 units (95% confidence interval [CI] 2.2-3.9) for each unit change in the PHC question. Method 2: the mean change in PCS score increased by 2.1 units (95% CI 1.4-2.8) for each unit change in the PHC question. Method 3: the MCID was estimated to be 1.8 units. CONCLUSIONS: Our estimate of the MCID for the PCS in patients with stroke was 1.8 to 3.0 units.

The effect of the Take Charge intervention on mood, motivation, activation and risk factor management: Analysis of secondary data from the Taking Charge after Stroke (TaCAS) trial.

OBJECTIVE: To use secondary data from the Taking Charge after Stroke study to explore mechanisms for the positive effect of the Take Charge intervention on physical health, advanced activities of daily living and independence for people after acute stroke. DESIGN: An open, parallel-group, randomised trial with two active and one control intervention and blinded outcome assessment. SETTING: Community. PARTICIPANTS: Adults (n = 400) discharged to community, non-institutional living following acute stroke. INTERVENTIONS: One, two, or zero sessions of the Take Charge intervention, a self-directed rehabilitation intervention which helps a person with stroke take charge of their own recovery. MEASURES: Twelve months after stroke: Mood (Patient Health Questionnaire-2, Mental Component Summary of the Short Form 36); 'ability to Take Charge' using a novel measure, the Autonomy-Mastery-Purpose-Connectedness (AMP-C) score; activation (Patient Activation Measure); body mass index (BMI), blood pressure (BP) and medication adherence (Medication Adherence Questionnaire). RESULTS: Follow-up was near-complete (388/390 (99.5%)) of survivors at 12 months. Mean age (SD) was 72.0 (12.5) years. There were no significant differences in mood, activation, 'ability to Take Charge', medication adherence, BMI or BP by randomised group at 12 months. There was a significant positive association between baseline AMP-C scores and 12-month outcome for control participants (1.73 (95%CI 0.90 to 2.56)) but not for the Take Charge groups combined (0.34 (95%CI -0.17 to 0.85)). CONCLUSION: The mechanism by which Take Charge is effective remains uncertain. However, our findings support a hypothesis that baseline variability in motivation, mastery and connectedness may be modified by the Take Charge intervention.

Assessing the quality of decision-making for planned oocyte cryopreservation.

PURPOSE: This survey study aims to examine the quality of planned oocyte cryopreservation (POC) decision-making in the domains of decision change, decision difficulty, decision regret and informed choice. METHODS: Of the 224 women who completed at least one POC cycle between 2012 and 2018 at a Canadian academic IVF centre, 198 were reachable by email for anonymous survey participation. RESULTS: Ninety-eight questionnaires were returned (response rate 49.5%). Of these, 86 fully completed questionnaires were analyzed for this study. Eighty-eight percent of respondents stated that it was a 'good decision' to cryopreserve oocytes, in retrospect. Despite this, 31% found the decision-making process to be 'difficult'. Three in five (61%) would have made 'exactly the same' decision without any change, yet slightly over a third (35%) would have made a 'similar' decision, but with option-related changes and process-related changes. A negative correlation between 'decision regret' and 'informed choice' was found (p < .005). Those who stated that they would have made exactly the 'same' POC decision were found to have a significantly higher 'informed choice' score compared to others who would have made a 'similar' or 'completely different' decision, in retrospect (p < .001). Respondents with lesser 'decision regret' were significantly more likely to appraise their decision as a well-informed choice (p < .001). CONCLUSIONS: Our findings show that high-quality POC decision-making is accompanied by the perception of being able to make an informed choice, which can be achieved by providing patients with adequate information and individualized counselling to help patients set realistic expectations of cycle outcomes.

Parenthood desire, childbearing plans and oocyte utilization among women who previously underwent planned oocyte cryopreservation.

RESEARCH QUESTION: To examine the motivations, life circumstances and parenthood aspirations of a cohort of women who underwent planned oocyte cryopreservation (POC) at a Canadian academic IVF centre. DESIGN: A single-site, cross-sectional, anonymous quantitative study using a study-specific questionnaire administrated via SurveyMonkey®. Of the 224 women who completed at least one POC cycle between 2012 and 2018, 198 were reached by email and invited to participate. RESULTS: Of the 98 (49.5%) questionnaires returned, 86 were fully completed and were analysed. Mean age at first POC cycle was 35.7 ± 2.4 (range 27-43) and at survey was 37.7 ± 2.5 years. At POC, 77% were single and 97.7% childless. At survey, 96% had not attempted to use their cryopreserved oocytes, yet 26 (30%) had tried natural conception or fertility treatments. Of these, three conceived naturally and two by assisted reproduction. Eighty-five per cent expressed a strong motherhood desire and 67.1% indicated that usage of their cryopreserved oocytes was mostly contingent on relationship status. Many expressed a desire for shared genetic parenthood within a committed relationship. Forty-seven per cent did not want to carry a pregnancy beyond the age of 46. CONCLUSION: The findings of this study confirm the central role of age and relationship status in influencing women's POC decisions and oocyte utilization plans. The late age at POC could be explained by women using it toward the end of their peak reproductive years to leverage their remaining chances of genetic motherhood. Surveying women at later points following POC would help to gain a more comprehensive picture of their oocyte utilization and disposition plans.

Tales from the Cryptkeeper: New Roles for Lats1/2 in Wnt-driven Homeostasis.

In this issue of Cell Stem Cell, Li et al. (2020) reveal pivotal roles for Lats1/2 in adult, Wnt-mediated intestinal homeostasis through TEAD-dependent and -independent transcription. Loss of Lats1/2 mobilizes a previously unrecognized YAP/TAZ-Groucho/TLE interaction to suppress Wnt/TCF-mediated transcription, thereby resulting in intestinal stem cell depletion and Wnt-uncoupled progenitor expansion.

Taking Charge after Stroke: A randomized controlled trial of a person-centered, self-directed rehabilitation intervention.

BACKGROUND AND PURPOSE: "Take Charge" is a novel, community-based self-directed rehabilitation intervention which helps a person with stroke take charge of their own recovery. In a previous randomized controlled trial, a single Take Charge session improved independence and health-related quality of life 12 months following stroke in Maori and Pacific New Zealanders. We tested the same intervention in three doses (zero, one, or two sessions) in a larger study and in a broader non-Maori and non-Pacific population with stroke. We aimed to confirm whether the Take Charge intervention improved quality of life at 12 months after stroke in a different population and whether two sessions were more effective than one. METHODS: We randomized 400 people within 16 weeks of acute stroke who had been discharged to institution-free community living at seven centers in New Zealand to a single Take Charge session (TC1, n = 132), two Take Charge sessions six weeks apart (TC2, n = 138), or a control intervention (n = 130). Take Charge is a "talking therapy" that encourages a sense of purpose, autonomy, mastery, and connectedness with others. The primary outcome was the Physical Component Summary score of the Short Form 36 at 12 months following stroke comparing any Take Charge intervention to control. RESULTS: Of the 400 people randomized (mean age 72.2 years, 58.5% male), 10 died and two withdrew from the study. The remaining 388 (97%) people were followed up at 12 months after stroke. Twelve months following stroke, participants in either of the TC groups (i.e. TC1 + TC2) scored 2.9 (95% confidence intervals (CI) 0.95 to 4.9, p = 0.004) points higher (better) than control on the Short Form 36 Physical Component Summary. This difference remained significant when adjusted for pre-specified baseline variables. There was a dose effect with Short Form 36 Physical Component Summary scores increasing by 1.9 points (95% CI 0.8 to 3.1, p < 0.001) for each extra Take Charge session received. Exposure to the Take Charge intervention was associated with reduced odds of being dependent (modified Rankin Scale 3 to 5) at 12 months (TC1 + TC2 12% versus control 19.5%, odds ratio 0.55, 95% CI 0.31 to 0.99, p = 0.045). CONCLUSIONS: Confirming the previous randomized controlled trial outcome, Take Charge-a low-cost, person-centered, self-directed rehabilitation intervention after stroke-improved health-related quality of life and independence. CLINICAL TRIAL REGISTRATION-URL: http://www.anzctr.org.au. Unique identifier: ACTRN12615001163594.

YAP and TAZ regulate cell volume.

How mammalian cells regulate their physical size is currently poorly understood, in part due to the difficulty in accurately quantifying cell volume in a high-throughput manner. Here, using the fluorescence exclusion method, we demonstrate that the mechanosensitive transcriptional regulators YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are regulators of single-cell volume. The role of YAP/TAZ in volume regulation must go beyond its influence on total cell cycle duration or cell shape to explain the observed changes in volume. Moreover, for our experimental conditions, volume regulation by YAP/TAZ is independent of mTOR. Instead, we find that YAP/TAZ directly impacts the cell division volume, and YAP is involved in regulating intracellular cytoplasmic pressure. Based on the idea that YAP/TAZ is a mechanosensor, we find that inhibiting myosin assembly and cell tension slows cell cycle progression from G1 to S. These results suggest that YAP/TAZ may be modulating cell volume in combination with cytoskeletal tension during cell cycle progression.

GPCR signaling inhibits mTORC1 via PKA phosphorylation of Raptor.

The mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth, metabolism, and autophagy. Extensive research has focused on pathways that activate mTORC1 like growth factors and amino acids; however, much less is known about signaling cues that directly inhibit mTORC1 activity. Here, we report that G-protein coupled receptors (GPCRs) paired to Gαs proteins increase cyclic adenosine 3'5' monophosphate (cAMP) to activate protein kinase A (PKA) and inhibit mTORC1. Mechanistically, PKA phosphorylates the mTORC1 component Raptor on Ser 791, leading to decreased mTORC1 activity. Consistently, in cells where Raptor Ser 791 is mutated to Ala, mTORC1 activity is partially rescued even after PKA activation. Gαs-coupled GPCRs stimulation leads to inhibition of mTORC1 in multiple cell lines and mouse tissues. Our results uncover a signaling pathway that directly inhibits mTORC1, and suggest that GPCRs paired to Gαs proteins may be potential therapeutic targets for human diseases with hyperactivated mTORC1.

Low genetic diversity in captive populations of the critically endangered Blue-crowned Laughingthrush (Garrulax courtoisi) revealed by a panel of novel microsatellites.

BACKGROUND: Captive populations permit research and conservation of endangered species in which these efforts are hardly implemented in wild populations. Thus, analysing genetic diversity and structure of captive populations offers unique opportunities. One example is the critically endangered Blue-crowned Laughingthrush, Garrulax courtoisi, which has only two known wild populations in Wuyuan, Jiangxi and Simao, Yunnan, China. We carried out the first conservation genetic study, in order to provide useful implications that allow for successful ex situ conservation and management of the Blue-crowned Laughingthrush. METHODS: Using the novel microsatellite markers developed by whole-genome sequencing, we genotyped two captive populations, from the Ocean Park Hong Kong, which are of unknown origin, and the Nanchang Zoo, which were introduced from the Wuyuan wild population since the year 2010-2011, respectively. The genetic diversity of captive Blue-crowned Laughingthrush populations was estimated based on genetic polymorphisms revealed by a new microsatellite data set and mitochondrial sequences. Then, we characterised the population structure using STRUCTURE, principal coordinates analysis, population assignment test using the microsatellite data, and haplotype analysis of mitochondrial data. Additionally, we quantified genetic relatedness based on the microsatellite data with ML-Relate. RESULTS: Our results showed equally low levels of genetic diversity of the two captive Blue-crowned Laughingthrush populations. The population structure analysis, population assignment test using the microsatellite data, and haplotype analysis of the mitochondrial data showed weak population structuring between these two populations. The average pairwise relatedness coefficient was not significant, and their genetic relatedness was quantified. DISCUSSION: This study offers a genetic tool and consequently reveals a low level of genetic diversity within populations of a critically endangered bird species. Furthermore, our results indicate that we cannot exclude the probability that the origin of the Hong Kong captive population was the wild population from Wuyuan. These results provide valuable knowledge that can help improve conservation management and planning for both captive and wild Blue-crowned Laughingthrush populations.

The Taking Charge After Stroke (TaCAS) study protocol: a multicentre, investigator-blinded, randomised controlled trial comparing the effect of a single Take Charge session, two Take Charge sessions and control intervention on health-related quality of life 12 months after stroke for non-Maori, non-Pacific adult New Zealanders discharged to community living.

INTRODUCTION: Stroke is one of the leading causes of disability worldwide. Recent data support the possibility that person-centred, self-management interventions can reduce dependence after stroke. However, there is limited information on the generalisability and optimum dose of these interventions. METHODS: The Taking Charge After Stroke (TaCAS) study is a multicentre, investigator-blinded, randomised controlled trial recruiting 400 participants following acute stroke from seven hospitals in New Zealand. All patients discharged to community living who have ongoing symptoms at time of discharge (modified Rankin scale>0) will be eligible. Participants will be randomly assigned to one Take Charge session, two Take Charge sessions 6 weeks apart or control. OUTCOMES: The primary outcome will be the Physical Component Summary score of the Short-Form 36 at 12 months post stroke. Secondary outcomes will include dependence (modified Rankin scale), performance in activities of daily living (Barthel Index) and carer strain (Caregiver Strain Index), at 6 and 12 months post stroke. All analyses will be conducted on an intention-to-treat basis. ETHICS AND DISSEMINATION: The TaCAS study is funded by a Health Research Council of New Zealand grant. It has been approved by the Central Health and Disability Ethics Committee (15/CEN/115). Results will be published and presented at relevant stroke meetings within New Zealand and internationally, informing the use of a self-management intervention after stroke. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry ACTRN12615001163594. Date registered 02-11-2015. Medical Research Institute of New Zealand Registry TCS01. Universal trial number U1111-1171-4127.

The Hippo pathway in organ development, homeostasis, and regeneration.

The Hippo pathway is a universal governor of organ size, tissue homeostasis, and regeneration. A growing body of work has advanced our understanding of Hippo pathway regulation of cell proliferation, differentiation, and spatial patterning not only in organ development but also upon injury-induced regeneration. The pathway's central role in stem cell biology thus implicates its potential for therapeutic manipulation in mammalian organ regeneration. In this review, we survey recent literature linking the Hippo pathway to the development, homeostasis, and regeneration of various organs, including Hippo-independent roles for YAP, defined here as YAP functions that are not regulated by the Hippo pathway kinases LATS1/2.