Community Culture Survey - Revised: Measuring neighborhood culture and exploring geographic, socioeconomic, and cultural determinants of health in samples across the United States and in Thailand.

Objectives: Research on links between social, geographic, and cultural determinants of health has been thwarted by inadequate measures of culture. The purpose of this study was to improve the measurement of community culture, defined as shared patterns of attitudes and behaviors among people within a neighborhood that distinguish it from others, and to examine dimensions of culture, independent of socioeconomic and demographic factors, and their relationships with health. Study design: A survey research design with correlational analyses was used. Methods: A survey packet including the Community Culture Survey - Revised (CCS-R), demographic, health, and other individual-level measures was administered through convenience sampling across the United States (US) and to a sample in Thailand from 2016 to 2018. US county-level variables were obtained from zip codes. Results: 1930 participants from 49 US states (n = 1592) and Thailand (n = 338) completed all CCS-R items, from which 12 subscales were derived: Social Support & Connectedness, Responsibility for Self & Others, Family Ties & Duties, Social Distress, Urban Diversity, Discontinuity, Church-Engaged, External Resource-Seeking, Locally Owned Business-Active, Power Deference, Next Generation Focus, and Self-Reliance. Neighborhood culture subscale scores varied more by geography than by participant's demographics. All subscales predicted one or more health indicator, and some of these relationships were significant after adjusting for participant age and county-level socioeconomic variables. Most of the significant differences on subscales by race/ethnicity were no longer significant after adjusting for participant's age and county-level socioeconomic variables. Most rural/urban and regional differences in culture within the US persisted after these adjustments. Based on correlational analyses, Social Support & Connectedness and Responsibility for Self & Others were the best predictors of participants' overall health and quality of life, and Responsibility for Self & Others was the best predictor (inversely) of the CDC's measures of social vulnerability. Conclusions: Neighborhood culture is measurable, multi-dimensional, distinct from race/ethnicity, and related to health even after controlling for age and socioeconomic factors. The CCS-R is useful for advancing research and practice addressing the complex interactions between individuals, their neighborhood communities, and health outcomes.

"Walk me through the final day": A thematic analysis study on the family caregiver experience of the Medical Assistance in Dying procedure day.

BACKGROUND: Legalization of assisted dying is progressively expanding worldwide. In Canada, the Medical Assistance in Dying Act became law in 2016. As assisted dying regulations evolve worldwide, comprehending its subjective impact and broader consequences, especially on family members, becomes pivotal for shaping practice, policy, and training. AIM: The goal of this study is to understand the experience of family caregivers on the assisted dying procedure day. DESIGN: Qualitative, thematic analysis, research using semi-structured interviews. SETTING/PARTICIPANTS: Family caregivers of patients who received assisted dying in two hospitals in Canada were recruited. Interviews were conducted at least 6 months after patient death. Conceptual saturation was achieved after analyzing 18 interviews. RESULTS: While caregivers expressed gratitude for the availability of Medical Assistance in Dying, they also described the procedure day as potentially jarring and unsettling. We identified five aspects that shaped their experience: attuned support from the clinical team; preparation for clinical details; congruence between the setting and the importance of the event; active participation and ceremony; and pacing and timing of the procedure. Together, these aspects impacted the level of uneasiness felt by caregivers on the procedure day. CONCLUSIONS: This study emphasized the importance of a family-centered approach to delivering Medical Assistance in Dying. It underscored recognizing the needs of family caregivers during the procedure day and offering strategies to ease their experience. Healthcare providers in jurisdictions where assisted dying is legal or deliberated should consider the applicability of these findings to their unique context.

Managing cancer and living meaningfully (CALM): Implementation in Dutch cancer care.

OBJECTIVE: Managing Cancer and Living Meaningfully (CALM) is a brief, evidence-based psychotherapy tailored for patients with advanced cancer that has not yet been implemented routinely in Dutch cancer care. The aim of this study was to assess the feasibility, acceptability, sustainability and effectiveness of CALM in different clinical settings in the Netherlands. METHODS: In 2019 and 2020 a multi-center, intervention-only study was performed in three Dutch cancer care settings. Professionals were trained to provide CALM under supervision. Patients diagnosed with advanced cancer were included and filled out questionnaires to measure depression (Patient Health Questionnaire-9), death anxiety (Death and Dying Distress Scale), and anxiety (hospital anxiety and depression scale-anxiety) at baseline, 3 and 6 months. The Clinical Evaluation Questionnaire was used to assess acceptability of CALM at 3 and 6 months. RESULTS: Sixty-four patients (55% of the eligible patients) were included in the study and 85% of the included patients received 3 or more CALM sessions. Of the 24 trained therapists, 15 (63%) started providing CALM. Two years post-study, CALM was provided in each center by a total of 19 therapists. On average, patients perceived CALM to be at least somewhat helpful. A significant decrease in severity of depression (p = 0.006), death anxiety (p = 0.008), and anxiety (p = 0.024) was observed over time. CONCLUSIONS: This study shows that CALM therapy is feasible, acceptable, and sustainable in three Dutch cancer care settings, although not all predefined feasibility criteria for therapists were met. CALM can be effective in decreasing feelings of depression, anxiety, and death anxiety in patients with advanced cancer.

Examining Utilization of an Outpatient Telenutrition Service Across Primary Care Clinics in South Carolina.

Introduction: Limited research exists on outpatient telenutrition, and more evidence is needed on service utilization and program evaluation. This study explored service utilization trends and patterns of the Medical University of South Carolina (MUSC) Outpatient Telehealth Nutrition (OT Nutrition) service. Methods: De-identified patient service utilization data were obtained from MUSC's OT Nutrition administrative files (2012-2020). Service utilization (referrals, visits scheduled, consultations, no-shows, no-show rate) was measured at the clinic level and stratified by patient type (adult/pediatric) and clinic rurality (rural/urban). Data were analyzed using descriptive statistics and a K-means cluster analysis. Results: Service utilization (2012-2020) reflected 6,212 referrals, 3,993 visits scheduled, and 2,880 consultations across 56 clinics. Yearly utilization trends showed high variability with no statistically significant differences observed on univariate comparisons of patient type or clinic rurality. The introduction of the Direct-To-Consumer modality mitigated a 36.7% decrease in consultations during the COVID-19 pandemic in 2020. Results of a K-means cluster analysis (p < 0.001) indicated 7% (n = 4) of clinics were very high and high utilizers, 36% (n = 21) were moderate and low utilizers, and 53% (n = 31) were very low utilizers. Discussion: Telenutrition can be delivered effectively to patients without requiring travel outside patients' medical homes or residences. Although continued advocacy is necessary for South Carolina to expand telenutrition coverage, more research is needed to evaluate the OT Nutrition service. Cluster analysis is an effective tool for identifying statistically significant groupings of clinics based on service utilization and could be used with implementation science in future program evaluation.

The quality of death and dying of patients with advanced cancer in hospice care in Uganda and Kenya.

OBJECTIVES: Minimal information is available about the quality of dying and death in Uganda and Kenya, which are African leaders in palliative care. We investigated the quality of dying and death in patients with advanced cancer who had received hospice care in Uganda or Kenya. METHODS: Observational study with bereaved caregivers of decedents (Uganda: n = 202; Kenya: n = 127) with advanced cancer who had received care from participating hospices in Uganda or Kenya. Participants completed the Quality of Dying and Death questionnaire and a measure of family satisfaction with cancer care (FAMCARE). RESULTS: Quality of Dying and Death Preparation and Connectedness subscales were most frequently rated as good to almost perfect for patients in both countries (45.5% to 81.9%), while Symptom Control and Transcendence subscales were most frequently rated as intermediate (42.6% to 60.4%). However, 35.4% to 67.7% of caregivers rated overall quality of dying and overall quality of death as terrible to poor. Ugandan caregivers reported lower Preparation, Connectedness, and Transcendence (p < .001). Controlling for covariates, overall quality of dying was associated with better Symptom Control in both countries (p < .001) and Transcendence in Uganda (p = .010); overall quality of death, with greater Transcendence in Uganda (p = .004); and family satisfaction with care, with better Preparation in Uganda (p = .004). SIGNIFICANCE OF RESULTS: Findings indicate strengths in spiritual and social domains of the quality of dying and death in patients who received hospice care in Uganda and Kenya, but better symptom control is needed to improve this outcome in these countries.

Teaching Oncology Nurses a Psychosocial Intervention for Advanced Cancer: A Mixed-Methods Feasibility Study.

OBJECTIVES: Psychological interventions for advanced cancer patients are effective in decreasing distress but are not well integrated into cancer care. Oncology nurses are well positioned to deliver such interventions, and their participation may enhance professional satisfaction and wellbeing. Managing Cancer and Living Meaningfully (CALM) is an evidence-based psychotherapy supporting advanced cancer patients. A CALM-Nurses (CALM-N) training program was developed to teach oncology nurses the basics of CALM for use in daily practice. Feasibility and acceptability of CALM-N and its impact on professional wellbeing were assessed in this pilot study. DATA SOURCES: Fifty-five nurses attended CALM-N in three groups. Thirty-five nurses completed the first e-learning, 29 nurses (83%) attended the first group session, and 22 (63%) attended all sessions. At baseline, 35 questionnaires were collected. Response rate at follow-up was 63% for Jefferson Scale of Empathy (n=22), 66% for self-efficacy scale (n=23), and for subscales of Professional Quality of Life Scale burnout; 51% (n=18), secondary traumatic stress; 49% (n=17), compassion satisfaction; 57% (n=20). A statistically significant increase in self-efficacy was found, but there were no significant changes in PROQOL and empathy. Focus groups suggested CALM-N helped nurses' understanding of patients and nurse-patient communication and increased reflection and perspective taking. CONCLUSION: CALM-N is a feasible and acceptable intervention for oncology nurses, with the potential to improve nurse-patient communication and the nurses' reflective capacities. IMPLICATIONS FOR NURSING PRACTICE: CALM-N has the potential to improve the capacity of oncology nurses to provide psychosocial care for advanced cancer patients and its application to nursing practice merits further investigation.

Patient quality of life and caregiver experiences in ovarian cancer: How are they related?

PURPOSE: Patients with ovarian cancer and their spousal caregivers report similarities in health-related quality of life (HRQoL) and experiences throughout the cancer process. Previous research has reflected these shared experiences, demonstrating caregivers' capacity to accurately rate their patient-partner's HRQoL as a proxy. In response, this study examines associations between caregivers' perceptions of their patient-partner's HRQoL and their own caregiving responsibilities, consequences to well-being, and desired assistance from the healthcare system. This study will be beneficial when developing supports to assist caregivers throughout the cancer journey. METHODS: Using a cross-sectional survey design, spousal caregivers (N = 82) of patients with ovarian cancer completed measures on perceived patient HRQoL and caregiver experiences. Correlation analyses determined medical and sociodemographic covariates. A multivariate multiple regression was conducted using four proxy HRQoL functioning subscales and three factors of reported experiences as caregivers in cancer. Post-hoc univariate regression analyses were run on significant factors to assess the associations that exist. RESULTS: Caregiver-perceived patient physical functioning was significantly associated with more caregiving tasks after controlling for education, age, and stage of ovarian cancer, but no other HRQoL functioning scale (i.e., role, emotional, social) was associated with caregiver experiences. CONCLUSION: The study provides a unique perspective into the caregiver experience by attending to interpersonal factors in relation to caregiver experiences. Results may be able to guide interventions aimed at supporting caregivers through the cancer process by offering more assistance with tasks as their partner's physical condition worsens.

Commentary: Access to Psychedelics for Psychological Suffering at the End of Life - Prioritizing Our Priorities.

We agree with Kratina et al. (2023) that the problem of psychological suffering at the end of life deserves attention from a policy standpoint and that psychedelic therapies show promise in this clinical context. However, we argue the following in this rejoinder: (1) disproportionate attention to psychedelics may overstate the current evidence base, potentially diverting resources away from existing evidence-based programs; (2) a more pressing policy priority related to this public health problem is to address population-level inequities in accessing high-quality, early and holistic palliative care, including psychosocial care; and (3) discussions about expanded access to psychedelics must also foreground equity issues.

The impact of COVID-19 on the experiences of patients and their family caregivers with medical assistance in dying in hospital.

BACKGROUND: The COVID-19 pandemic and its containment measures have drastically impacted end-of-life and grief experiences globally, including those related to medical assistance in dying (MAiD). No known qualitative studies to date have examined the MAiD experience during the pandemic. This qualitative study aimed to understand how the pandemic impacted the MAiD experience in hospital of persons requesting MAiD (patients) and their loved ones (caregivers) in Canada. METHODS: Semi-structured interviews were conducted with patients who requested MAiD and their caregivers between April 2020 and May 2021. Participants were recruited during the first year of the pandemic from the University Health Network and Sunnybrook Health Sciences Centre in Toronto, Canada. Patients and caregivers were interviewed about their experience following the MAiD request. Six months following patient death, bereaved caregivers were interviewed to explore their bereavement experience. Interviews were audio-recorded, transcribed verbatim, and de-identified. Transcripts were analyzed using reflexive thematic analysis. RESULTS: Interviews were conducted with 7 patients (mean [SD] age, 73 [12] years; 5 [63%] women) and 23 caregivers (mean [SD] age, 59 [11] years; 14 [61%] women). Fourteen caregivers were interviewed at the time of MAiD request and 13 bereaved caregivers were interviewed post-MAiD. Four themes were generated with respect to the impact of COVID-19 and its containment measures on the MAiD experience in hospital: (1) accelerating the MAiD decision; (2) compromising family understanding and coping; (3) disrupting MAiD delivery; and (4) appreciating rule flexibility. CONCLUSIONS: Findings highlight the tension between respecting pandemic restrictions and prioritizing control over the dying circumstances central to MAiD, and the resulting impact on patient and family suffering. There is a need for healthcare institutions to recognize the relational dimensions of the MAiD experience, particularly in the isolating context of the pandemic. Findings may inform strategies to better support those requesting MAiD and their families during the pandemic and beyond.

Interventions to improve outcomes for caregivers of patients with advanced cancer: a meta-analysis.

BACKGROUND: Family caregivers of patients with advanced cancer often have poor quality of life (QOL) and mental health. We examined the effectiveness of interventions offering support for caregivers of patients with advanced cancer on caregiver QOL and mental health outcomes. METHODS: We searched Ovid MEDLINE, EMBASE, Cochrane CENTRAL, and Cumulative Index to Nursing and Allied Health Literature databases from inception through June 2021. Eligible studies reported on randomized controlled trials for adult caregivers of adult patients with advanced cancer. Meta-analysis was conducted for primary outcomes of QOL, physical well-being, mental well-being, anxiety, and depression, from baseline to follow-up of 1-3 months; secondary endpoints were these outcomes at 4-6 months and additional caregiver burden, self-efficacy, family functioning, and bereavement outcomes. Random effects models were used to generate summary standardized mean differences (SMD). RESULTS: Of 12 193 references identified, 56 articles reporting on 49 trials involving 8554 caregivers were eligible for analysis; 16 (33%) targeted caregivers, 19 (39%) patient-caregiver dyads, and 14 (29%) patients and their families. At 1- to 3-month follow-up, interventions had a statistically significant effect on overall QOL (SMD = 0.24, 95% confidence interval [CI] = 0.10 to 0.39); I2 = 52.0%), mental well-being (SMD = 0.14, 95% CI = 0.02 to 0.25; I2 = 0.0%), anxiety (SMD = 0.27, 95% CI = 0.06 to 0.49; I2 = 74.0%), and depression (SMD = 0.34, 95% CI = 0.16 to 0.52; I2 = 64.4) compared with standard care. In narrative synthesis, interventions demonstrated improvements in caregiver self-efficacy and grief. CONCLUSIONS: Interventions targeting caregivers, dyads, or patients and families led to improvements in caregiver QOL and mental health. These data support the routine provision of interventions to improve well-being in caregivers of patients with advanced cancer.

Minimizing Product Inhibition in DNA Self-Replication: Insights for Prebiotic Replication from the Role of the Enzyme in Lesion-Induced DNA Amplification.

Self-replication of nucleic acids in the absence of enzymes represents an important and poorly understood step in the origin of life as such reported systems are strongly hindered by product inhibition. Studying one of the few successful examples of enzymatic DNA self-replication based on a simple ligation chain reaction, lesion-induced DNA amplification (LIDA), can shed light on how this fundamental process may have originally evolved. To identify the unknown factors that lead LIDA to overcome product inhibition we have employed isothermal titration calorimetry and global fitting of time-dependent ligation data to characterize the individual steps of the amplification process. We find that incorporating the abasic lesion into one of the four primers substantially decreases the stability difference between the product and intermediate complexes compared with complexes without the abasic group. In the presence of T4 DNA ligase this stability gap is further reduced by two orders of magnitude revealing that the ligase also helps overcome product inhibition. Kinetic simulations reveal that the intermediate complex stability and the magnitude of the ligation rate constant significantly impact the rate of self-replication, suggesting that catalysts that both facilitate ligation and stabilize the intermediate complex might be a route to efficient nonenzymatic replication.

Quality of Dying and Death of Patients With Cancer in Hospice Care in Uganda.

PURPOSE: Despite advances in palliative care in Uganda, there has been relatively little recent patient-centered research investigating end-of-life outcomes in this region. We assessed the quality of dying and death of patients with cancer in hospice care in Uganda. METHODS: Bereaved caregivers of patients who received hospice care in Uganda and died 2-12 months earlier (N = 201) completed the Quality of Dying and Death Questionnaire, which includes 31 items and single-item ratings of overall quality of dying and moment of death, and the FAMCARE measure of family satisfaction with cancer care. RESULTS: Caregivers reported low-intermediate overall quality of dying (mean [M] standard deviation [SD], 3.25 [2.98]) and overall quality of moment of death (M [SD], 3.59 [3.51]), with 47.0% of the ratings of these two outcomes in the poor range, but the mean family satisfaction with care was high (M [SD], 77.75 [10.26]). Most Quality of Dying and Death Questionnaire items (74.2%) were rated within the intermediate range. Items rated within the good range were religious-spiritual, interpersonal, and personal facets; two items within the poor range reflected physical functioning. Overall quality of dying was most strongly correlated with pain control (Spearman's rho [rs] = 0.45, P < .001), and overall quality of moment of death with state of consciousness before death and being unafraid of dying (rs = 0.42, P < .001). The FAMCARE score was not correlated with overall quality of dying or moment of death (P = .576-.813). Only one FAMCARE item, information on managing patient's pain, was correlated with overall quality of moment of death (rs = -0.19, P = .008). CONCLUSION: End-of-life care in hospices in Uganda requires further improvement, particularly with regard to symptom control. Patient-centered data could bolster advocacy efforts to support quality improvement of palliative care in this and other countries.

Early palliative care and quality of dying and death in patients with advanced cancer.

OBJECTIVE: Early palliative care (EPC) in the outpatient setting improves quality of life for patients with advanced cancer, but its impact on quality of dying and death (QODD) and on quality of life at the end of life (QOL-EOL) has not been examined. Our study investigated the impact of EPC on patients' QODD and QOL-EOL and the moderating role of receiving inpatient or home palliative care. METHOD: Bereaved family caregivers who had provided care for patients participating in a cluster-randomised trial of EPC completed a validated QODD scale and indicated whether patients had received additional home palliative care or care in an inpatient palliative care unit (PCU). We examined the effects of EPC, inpatient or home palliative care, and their interactions on the QODD total score and on QOL-EOL (last 7 days of life). RESULTS: A total of 157 caregivers participated. Receipt of EPC showed no association with QODD total score. However, when additional palliative care was included in the model, intervention patients demonstrated better QOL-EOL than controls (p=0.02). Further, the intervention by PCU interaction was significant (p=0.02): those receiving both EPC and palliative care in a PCU had better QOL-EOL than those receiving only palliative care in a PCU (mean difference=27.10, p=0.002) or only EPC (mean difference=20.59, p=0.02). CONCLUSION: Although there was no association with QODD, EPC was associated with improved QOL-EOL, particularly for those who also received inpatient care in a PCU. This suggests a long-term benefit from early interdisciplinary palliative care on care throughout the illness. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (#NCT01248624).

Caring for the Family Caregiver: Development of a Caregiver Clinic at a Cancer Hospital as Standard of Care.

Family caregivers make significant contributions to the overall care of cancer patients and are the "invisible backbone" of the health care system. Family caregivers experience a wide range of challenges and can be considered patients in their own right, requiring support and dedicated attention, which may benefit them, the patients they are caring for, and the health care system. Despite consistent evidence on caregiver distress and unmet needs, most cancer care is organized around the patient as the target of care and caregiver distress is not screened for or addressed systematically. This article describes the development of a novel clinical, educational, and research program dedicated to supporting family caregivers at the Princess Margaret Cancer Center, Toronto, Canada and presents a model for a brief psychosocial intervention for caregivers. The objective of this article is to assist others in developing services to address the needs of family caregivers as a standard of care.

The Italian validation of the Death and Dying Distress Scale.

OBJECTIVES: Death anxiety (DA), a condition characterized by fear, angst, or panic related to the awareness of one's own death, is commonly observed in advanced cancer patients. The aim of this study was to examine the psychometric properties of the Italian version of the Death and Dying Distress Scale (DADDS-IT) in a sample of patients with advanced cancer. METHODS: The sample included 200 Italian advanced cancer patients meeting eligibility criteria to access palliative care. Patients' levels of DA were assessed by using the DADDS-IT, while the levels of depression, anxiety, demoralization, spiritual well-being, and symptom burden were assessed using the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Demoralization Scale, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale, and the Edmonton Symptom Assessment System, respectively; Karnofsky Performance Status was used to measure functional impairment. Confirmatory factor analyses (CFA) of previous structures and exploratory factor analyses (EFA) were conducted. RESULTS: CFA revealed that none of the previous structures adequately fitted data from our sample. EFA revealed a 4-factor model comprising Finitude (α = 0.91), Regret (α = 0.86), Dying (α = 0.88), and Relational Burden (α = 0.73), accounting for the 77.1% of the variance. Dying subscore was higher in hospice patients than in those recruited in medical wards. SIGNIFICANCE OF RESULTS: The present study provides further evidence that DA is a condition that deserves attention and that DADDS-IT shows good psychometric properties to support its use in research and clinical settings.

Achilles tendon thickness reduces immediately after a marathon.

BACKGROUND: The purpose of the present investigation was to evaluate the immediate effect of running a marathon on Achilles tendon anteroposterior thickness. METHODS: In 25 runners who took part in the London marathon, ultrasonography was used to measure the Achilles tendon thickness pre- and immediately post-marathon and to identify any structural abnormalities indicating tendinopathy. Pain was recorded using a numerical rating scale at baseline and post-marathon. Twenty-one participants were included in the final analysis. RESULTS: Running a marathon resulted in a significant decrease (- 13%, p < 0.01) in anteroposterior diameter of the Achilles tendon immediately following the marathon. There was no change in the proportion of Achilles tendons with structural abnormalities (34%) or pain (12%) following the marathon (p > 0.05). CONCLUSION: Running a marathon resulted in an immediate reduction in anteroposterior diameter of the Achilles tendon. This finding may have implications for injury prevention and recovery following a marathon.

Traumatic stress symptoms in family caregivers of patients with acute leukaemia: protocol for a multisite mixed methods, longitudinal, observational study.

INTRODUCTION: The diagnosis, progression or recurrence of cancer is often highly traumatic for family caregivers (FCs), but systematic assessments of distress and approaches for its prevention and treatment are lacking. Acute leukaemia (AL) is a life-threatening cancer of the blood, which most often presents acutely, requires intensive treatment and is associated with severe physical symptoms. Consequently, traumatic stress may be common in the FCs of patients with AL. We aim to determine the prevalence, severity, longitudinal course and predictors of traumatic stress symptoms in FCs of patients with AL in the first year after diagnosis, and to understand their lived experience of traumatic stress and perceived support needs. METHODS AND ANALYSIS: This two-site longitudinal, observational, mixed methods study will recruit 223 adult FCs of paediatric or adult patients newly diagnosed with AL from two tertiary care centres. Quantitative data will be collected from self-report questionnaires at enrolment, and 1, 3, 6, 9 and 12 months after admission to hospital for initial treatment. Quantitative data will be analysed using descriptive and machine learning approaches and a multilevel modelling (MLM) approach will be used to confirm machine learning findings. Semi-structured qualitative interviews will be conducted at 3, 6 and 12 months and analysed using a grounded theory approach. ETHICS AND DISSEMINATION: This study is funded by the Canadian Institutes of Health Research (CIHR number PJT 173255) and has received ethical approval from the Ontario Cancer Research Ethics Board (CTO Project ID: 2104). The data generated have the potential to inform the development of targeted psychosocial interventions for traumatic stress, which is a public health priority for high-risk populations such as FCs of patients with haematological malignancies. An integrated and end-of-study knowledge translation strategy that involves FCs and other stakeholders will be used to interpret and disseminate study results.

Numb regulates Tau levels and prevents neurodegeneration in tauopathy mouse models.

Accumulation of the microtubule-associated protein Tau is linked to neuronal cell death in tauopathies, but how intraneuronal Tau levels are regulated in health and disease remains unclear. Here, we show that conditional inactivation of the trafficking adaptor protein Numb in retinal ganglion cells (RGCs) increases Tau levels and leads to axonal blebbing, which is followed by neuronal cell loss in aged mice. In the TauP301S mouse model of tauopathy, conditional inactivation of Numb in RGCs and spinal motoneurons accelerates neurodegeneration, and loss of Numb in motoneurons also leads to precocious hindlimb paralysis. Conversely, overexpression of the long isoform of Numb (Numb-72) decreases intracellular Tau levels and reduces axonal blebbing in TauP301S RGCs, leading to improved electrical activity in cultured neurons and improves performance in a visually guided behavior test in vivo. These results uncover Numb as a key regulator of intracellular Tau levels and identify Numb-72 as a potential therapeutic factor for tauopathies.