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Background: A theoretical interaction exists between human immunodeficiency virus (HIV) antiretroviral (ARV) agents and direct oral anticoagulants (DOACs), although the clinical significance is unclear. Objective: This study aimed to assess characteristics, prescribing patterns, and outcomes associated with concomitant therapy. Methods: A single-center, retrospective review was performed on patients older than 18 years prescribed a DOAC for any indication with concurrent interacting ARV(s) from June 2016 through June 2019. The primary endpoint was to assess prescribing and population characteristics. Secondary endpoints were to evaluate safety outcomes, DOAC level monitoring, readmissions, outpatient follow-up, and DOAC modification interventions. Results: Thirty-six patients (72 hospital admissions) were identified. The most common DOAC was apixaban (83.3%) and ARV was ritonavir (50%). Of the 72 encounters, 26 (36.1%) DOACs were dosed appropriately per guideline recommendations. Twenty pharmacy interventions for therapy modification were recognized. Eleven (30.6%) patients experienced bleeding and 2 (5.6%) thrombosis. Of the adverse events, all patients had renal impairment. Conclusions: As DOAC utilization grows, increasing use in HIV could be expected. More frequent adjustment or avoidance is recommended per guidelines. Our data suggest the majority of patients receive CYP3A4-inhibiting regimens. Caution should be employed with renal insufficiencies. Further studies are warranted to assess safety and efficacy within this population.

Purpose The causal link between chemotherapy and cognitive impairment is unclear. We studied testicular cancer patients' objective and subjective cognitive function longitudinally, comparing a surgery group with a surgery + chemotherapy group,addressing prior methodological issues using a computerized test to limit assessment issues, and controlling for confounding variables.Methods: Prospectively, of 145 patients from16 centres with sufficient data, n = 61 receiving surgery + chemotherapy (etoposide and cisplatin ± bleomycin, BEP/EP; or single agent carboplatin) were compared to n = 41 receiving surgery alone. CogHealth assessed six objective cognitive tasks. The Cognitive Failures Questionnaire assessed self-perceived cognitive dysfunction. The Functional Assessment of Chronic Illness Therapy-Fatigue and the Hospital Anxiety and Depression Scale assessed psychological influences. Linear mixed models compared changes from baseline (< 6 months post-surgery/pre-chemotherapy) to follow-up(12-18 months post-baseline), controlling covariates. Results: There were no significant interaction effects for five objective cognitive function tasks suggesting that changes over time were not due to group membership. However, psychomotor function (controlling for age) and physical well-being were significantly worse for the chemotherapy versus the surgery group at baseline, with groups converging by follow-up. Groups showed no differences in subjective cognitive dysfunction. The chemotherapy group showed higher anxiety, poorer functional well-being and worse fatigue compared to the surgery-only group at baseline, but not by follow-up. For both groups, emotional well-being,functional well-being and anxiety significantly improved over time.Conclusion: No substantive differences in objective or subjective cognitive dysfunction in either group persisted 12-18 months post-baseline. Patients undergoing chemotherapy for testicular cancer differ from findings in breast cancer populations. Refereed/Peer-reviewed

PURPOSE: Relatively little is known about caregivers of African American cancer survivors. Our goal was to identify the extent of burden among this group of caregivers. METHODS: Responses from 560 informal caregivers of African American participants of the Research on Cancer Survivors (ROCS) study in Detroit, MI were analyzed including demographics, assistance provided including Activities of Daily Living (ADLs) and Instrumental Activities of Daily Living (IADLs), time spent in caregiving, and caregiver burden (CGB). We assessed relationships between CGB and demographic variables, ADLs/IADLs and level of care. Multivariable logistic regression determined which ADLs and IADLs were associated with high CGB. RESULTS: Over 75% of caregivers were female and 97% identified as African American. Mean age was 52.6 years. Fifty-six percent were employed outside the home and 90% were related to the survivor. Caregivers averaged 35.7 hours/week providing care, assisting with on average 2.8 ADLs and 5.0 IADLs. Despite the many hours and activities reported, no caregivers rated CGB as severe; only 4% rated it moderate to severe. ADLs associated with the top quartile of CGB were feeding and toileting; IADLs were finances, telephoning, housework, and medications. CONCLUSIONS: Caregivers for African American cancer survivors provide many hours of care, yet most describe their CGB as low. Although ADL assistance is often available through the healthcare system, assistance with IADLs presents an opportunity to lessen the burden for these caregivers and their care recipients. IMPLICATIONS FOR CANCER SURVIVORS: African American cancer survivors receive much care from informal family caregivers, who assist with multiple ADLs and IADLs. Formal IADL assistance programs, similar to those available for ADLs, would benefit both survivors and caregivers.

Increased involvement of the hip musculature during some movements is associated with enhanced performance and reduced injury risk. However, the impact of hip dominant weight training methods on movement strategy has seen limited attention within the literature. The aim of this study was to evaluate if a 9-week hip dominant weight training intervention promotes a more hip dominant movement strategy leading to an improvement in countermovement jump performance. Twenty-two experienced female dancers were recruited and separated into an intervention (age 24.4 ± 6.3 years, body height 165.5 ± 5.8 cm, body mass 65.9 ± 5.6 kg) and a control (age 22.9 ± 5.6 years, body height 163.3 ± 5.4 cm, body mass 57.4 ± 6.8 kg) group. The intervention group participated in a 9-week hip dominant training intervention, which consisted of a wide stance back squat, Romanian deadlift, hip thrusters, and a bent over row. Hip and knee kinematics and kinetics, and countermovement jump performance were assessed pre and post training. Significant interaction effects were found for peak hip joint moment (p = 0.030, η2 = 0.214) and countermovement jump performance (p = 0.003, η2 = 0.356), indicating an increase in peak hip joint moment and countermovement jump performance for the intervention group. Specifically, the intervention group showed a mean increase in jump height of 11.5%. The data show that the use of a hip dominant weight training strategy can improve hip contribution in the propulsion phase of the countermovement jump. Strength and conditioning specialists should incorporate hip dominant weight training exercises to increase hip strength and improve performance.

PURPOSE: Caregivers of cancer survivors may need to take time off work or make other employment changes to handle caregiving demands. Work impacts of caregiving, financial burden, and psychosocial outcomes of caregivers are not well understood. METHODS: Results include information from surveys completed by 202 employed caregivers of participants in the Detroit Research on Cancer Survivors cohort, a population-based cohort of African American survivors of breast, colorectal, lung, or prostate cancer. Relationships between work outcomes, financial burden, and anxiety and depression were assessed using logistic regression models controlling for demographic and cancer-related factors. RESULTS: Most (73.8%) caregivers made some employment change. Sixty percent changed their schedule, hours, duties, or employment status; 15.3% took at least 1 month off to provide care, and 38% reported difficulty balancing work and caregiving. Employment changes were strongly associated with difficulty balancing work and caregiving (odds ratio [OR], 5.83; 95% CI, 2.38 to 14.0) and financial burden (OR, 2.12; 95% CI, 1.05 to 4.27). Difficulty balancing work and caregiving was associated with symptoms of anxiety (OR, 1.86; 95% CI, 1.01 to 3.43) and depression (OR, 2.40; 95% CI, 1.16 to 4.96). High ( v low) financial burden was associated with symptoms of anxiety (OR, 2.85; 95% CI, 1.01 to 8.06). CONCLUSION: Difficulty balancing work and caregiving is common among caregivers of African American cancer survivors and is associated with symptoms of depression and anxiety. Supports for caregivers facing employment challenges may improve their psychosocial well-being.

Background Coronavirus disease 2019 (COVID‐19) has had profound effects on population health to date. African American cancer survivors are particularly vulnerable to developing severe consequences; therefore, understanding the impact of the virus on this patient population is critical. Methods The Detroit Research on Cancer Survivors cohort is a unique effort to understand the determinants of poor outcomes in African American cancer survivors. To date, more than 4500 cancer survivors and nearly 950 primary caregivers have been enrolled; participation includes a survey and the collection of biospecimens, medical records, and tumor tissue. Beginning in the spring of 2020, a supplemental survey focusing on the impact of COVID‐19 was offered to enrolled participants. The analysis included 890 survivors. Results Nearly all survivors (>99%) reported changes in their daily activities in an effort to reduce the risk of infection. More than 40% of the survivors reported some disruption in their access to medical care. A substantial proportion of the survivors (>40%) reported feeling anxious, depressed, and/or isolated during the COVID‐19 pandemic. Approximately 40% of the patients reported changes in health behaviors shown to negatively affect survivorship outcomes (physical inactivity, smoking, and alcohol use) as a result of the pandemic. Conclusions The influence of the COVID‐19 pandemic on African American cancer survivors is substantial: it has affected both their physical and mental health. Coupled with changes in health behaviors, these factors will likely affect outcomes in this high‐risk patient population, and this makes further study and interventions necessary to mitigate the long‐term impact of the pandemic on cancer outcomes., The COVID‐19 pandemic has had a profound impact on the physical and mental health of African American cancer survivors living in Detroit, Michigan. Strategies focusing on health behaviors such as physical activity would improve patient health and quality of life.

Objective Chemotherapy-induced nausea is challenging to predict and treat. Research indicates that pretreatment psychological variables including patients' perceptions of their susceptibility to nausea, expectancies of treatment-related nausea and nausea history (i.e., motion sickness, morning sickness and baseline levels of nausea) may aid in predicting nausea severity during chemotherapy. However, this research is dated and limited in quantity. We investigated whether psychological variables could improve prediction of nausea severity to inform interventions targeting chemotherapy-induced nausea. Methods In this secondary analysis, a subgroup of women receiving chemotherapy (for the first time) for breast cancer completed pretreatment measures: perceived nausea susceptibility, nausea expectancies, nausea history and baseline nausea. They rated subsequent nausea severity across 4-days, during treatment and posttreatment in a self-report diary. Structural Equation Modelling was used to explore associations. Results Across the women (N = 481), perceived nausea susceptibility predicted subsequent nausea severity (β = 0.16), but nausea expectancies did not (β = 0.05). Nausea history variables demonstrated small-moderate associations with perceived susceptibility (β = 0.21-0.32) and negligible-small associations with nausea expectancies (β = 0.07-0.14). Conclusion Perceived nausea susceptibility appears to capture patients' nausea history, to a degree, and is related to nausea severity during treatment. This is an important variable to include in pretreatment prediction of patients at risk of severe nausea.

Racial disparities in cancer incidence and outcomes are well-documented in the US, with Black people having higher incidence rates and worse outcomes than White people. In this review, we present a summary of almost 30 years of research conducted by investigators at the Karmanos Cancer Institute’s (KCI’s) Population Studies and Disparities Research (PSDR) Program focusing on Black-White disparities in cancer incidence, care, and outcomes. The studies in the review focus on individuals diagnosed with cancer from the Detroit Metropolitan area, but also includes individuals included in national databases. Using an organizational framework of three generations of studies on racial disparities, this review describes racial disparities by primary cancer site, disparities associated with the presence or absence of comorbid medical conditions, disparities in treatment, and disparities in physician-patient communication, all of which contribute to poorer outcomes for Black cancer patients. While socio-demographic and clinical differences account for some of the noted disparities, further work is needed to unravel the influence of systemic effects of racism against Black people, which is argued to be the major contributor to disparate outcomes between Black and White patients with cancer. This review highlights evidence-based strategies that have the potential to help mitigate disparities, improve care for vulnerable populations, and build an equitable healthcare system. Lessons learned can also inform a more equitable response to other health conditions and crises.

OBJECTIVE Immune checkpoint inhibitors (ICIs) perturb T-cell regulatory pathways to enhance antitumor immunity. However, an increase reporting of ICI-associated diabetes is observed in adults. To our knowledge, no cases have been reported in the pediatric population. RESEARCH DESIGN AND METHODS We describe a pediatric case of ICI-associated type 1 diabetes in a 12-year-old Hispanic boy with Hodgkin lymphoma. The patient had a history of autologous hematopoietic stem cell transplantation and was treated with pembrolizumab after disease progression. RESULTS The patient was admitted for diabetic ketoacidosis after five cycles of pembrolizumab. The patient was discharged with daily insulin injections and has continued on exogenous insulin ever since. CONCLUSIONS The expanded ICI use may lead to more cases in pediatric patients as has been observed in adults. Considering the acute manifestation of diabetes and the added burden of lifelong insulin therapy, in particular for pediatric patients and their families, monitoring and education of ICI-associated diabetes in children is needed.

BACKGROUND: Screening colonoscopy (SC) for colorectal cancer (CRC) is underused by Latinos. This randomized-clinical trial examined the impact of three interventions: 1) patient navigation, 2) patient navigation plus standard CDC print materials, and 3) patient navigation plus culturally-targeted print materials for Latinos referred for SC. Demographic, personal/health history, and psychometric factors associated with SC were also explored. METHODS: Urban Latinos (N=344) ages 50 to 85 with no personal/immediate family history of CRC before age 60, no personal history of gastrointestinal disorder, no colonoscopy in the past five years, with insurance coverage, and a referral for SC were consented. Participants were randomized to patient navigation (20%), patient navigation plus standard CDC print materials (40%), and patient navigation plus culturally-targeted print materials (40%). Completion of SC was assessed at 12 months. RESULTS: The interventions had an overall SC rate of 82%. Counterintuitively, patients with an average income less than $10,000 had higher SC rates (87%) than those with greater income (75%). CONCLUSION: The addition of standard or culturally-targeted print materials did not increase SC rates above that of patient navigation. Indeed, after controlling for other variables, culturally-targeted print materials were associated with lower SC rates for Puerto Ricans. CONDENSED ABSTRACT: This randomized-clinical trial found that patient navigation led to high SC rates among Latinos. Adding print materials did not increase SC rates above that of patient navigation alone.

Peer-reviewed articles (n = 124) examining associations between medical mistrust (MM) and health outcomes from four databases, between January 1998 and May 2018, were reviewed; 36 qualitative and 88 quantitative studies met the inclusion criteria. The Williams and Mohammed framework guided our narrative synthesis of the studies; it argues that basic causes (e.g., biased institutions) affect the social status of marginalized groups which in turn effects multiple proximal pathways leading to responses and poor health. Most studies were cross-sectional with US-based samples. The MM in qualitative studies were categorized as interpersonal (n = 30), systemic (n = 22), and/or vicarious (n = 18); 25% did not explicitly note the basic causes of MM and race/ethnicity was often confounded with socioeconomic status (SES). All but three studies discussed an association between MM and a behavior response; no study focused on an actual health outcome. Most quantitative studies used multivariate regression analyses; only 15 of the 88 utilized advanced modeling techniques (e.g., mediation). Most (75%) studies did not describe basic causes for MM and 43% utilized low income samples. MM was conceptualized as a predictor/proximal pathway (in 73 studies) associated with a variety of responses, most commonly behavioral (e.g., diminished adherence); 14 studies found an association between MM and a specific health measure. This review underscores the need for future qualitative studies to place MM central to their research questions as in-depth descriptions of MM were limited. Future quantitative studies should replicate findings using more advanced analytical strategies that examine the relationship between MM and health outcomes.

Immune-checkpoint inhibition (ICI) has revolutionized treatment in cancers that are naturally immunogenic by enabling infiltration of T cells into the tumor microenvironment (TME) and promoting cytotoxic signaling pathways. Tumors possessing complex immunosuppressive TMEs such as breast and pancreatic cancers present unique therapeutic obstacles as response rates to ICI remain low. Such tumors often recruit myeloid-derived suppressor cells (MDSCs), whose functioning prohibits both T-cell activation and infiltration. We attempted to sensitize these tumors to ICI using epigenetic modulation to target MDSC trafficking and function to foster a less immunosuppressive TME. We showed that combining a histone deacetylase inhibitor, entinostat (ENT), with anti–PD-1, anti–CTLA-4, or both significantly improved tumor-free survival in both the HER2/neu transgenic breast cancer and the Panc02 metastatic pancreatic cancer mouse models. Using flow cytometry, gene-expression profiling, and ex vivo functional assays, we characterized populations of tumor-infiltrating lymphocytes (TILs) and MDSCs, as well as their functional capabilities. We showed that addition of ENT to checkpoint inhibition led to significantly decreased suppression by granulocytic MDSCs in the TME of both tumor types. We also demonstrated an increase in activated granzyme-B–producing CD8+ T effector cells in mice treated with combination therapy. Gene-expression profiling of both MDSCs and TILs identified significant changes in immune-related pathways. In summary, addition of ENT to ICI significantly altered infiltration and function of innate immune cells, allowing for a more robust adaptive immune response. These findings provide a rationale for combination therapy in patients with immune-resistant tumors, including breast and pancreatic cancers.

This survey study of adults residing in Michigan during June to December 2020 examines associations between race/ethnicity, medical mistrust within racial/ethnic groups, and willingness to participate in COVID-19 vaccine trials or to receive a COVID-19 vaccine., Key Points Question Is there an association between race/ethnicity and rejection of COVID-19 vaccine trial participation and vaccine uptake in the US, and does racial/ethnic group–based medical mistrust mediate this association? Findings In this survey study of 1835 adults in Michigan, Black participants reported the greatest medical mistrust among the racial/ethnic groups surveyed. Analysis of path models revealed significantly greater COVID-19 vaccine trial and uptake rejection among Black participants, which was partially mediated by medical mistrust. Meaning The findings suggest that racial/ethnic group–based medical mistrust may partially explain the association between Black race/ethnicity and rejection of COVID-19 vaccine trial participation and uptake, potentially informing socially and culturally responsive efforts to promote COVID-19 vaccination in this group., Importance The impact of COVID-19 in the US has been far-reaching and devastating, especially in Black populations. Vaccination is a critical part of controlling community spread, but vaccine acceptance has varied, with some research reporting that Black individuals in the US are less willing to be vaccinated than other racial/ethnic groups. Medical mistrust informed by experiences of racism may be associated with this lower willingness. Objective To examine the association between race/ethnicity and rejection of COVID-19 vaccine trial participation and vaccine uptake and to investigate whether racial/ethnic group–based medical mistrust is a potential mediator of this association. Design, Setting, and Participants This cross-sectional survey study was conducted from June to December 2020 using a convenience sample of 1835 adults aged 18 years or older residing in Michigan. Participants were recruited through community-based organizations and hospital-academic networks. Main Outcomes and Measures Separate items assessed whether respondents, if asked, would agree to participate in a research study to test a COVID-19 vaccine or to receive a COVID-19 vaccine. Participants also completed the suspicion subscale of the Group-Based Medical Mistrust Scale. Results Of the 1835 participants, 1455 (79%) were women, 361 (20%) men, and 19 (1%) other gender. The mean (SD) age was 49.4 (17.9) years, and 394 participants (21%) identified as Black individuals. Overall, 1376 participants (75%) reported low willingness to participate in vaccine trials, and 945 (52%) reported low willingness to be vaccinated. Black participants reported the highest medical mistrust scores (mean [SD], 2.35 [0.96]) compared with other racial/ethnic groups (mean [SD] for the total sample, 1.83 [0.91]). Analysis of path models revealed significantly greater vaccine trial and vaccine uptake rejection among Black participants (vaccine trial: B [SE], 0.51 [0.08]; vaccine uptake: B [SE], 0.51 [0.08]; both P

Alcohol is one of the most widely used drugs around the world, with many adverse health consequences well known to healthcare providers. This chapter provides an overview of the metabolism of alcohol and its short- and long-term effects. The socioeconomic factors impacting alcohol use are explored and consideration is given to variations in global consumption. Alcohol is a risk factor for many negative health behaviours and diseases, including violence, injury, sexually transmitted infections, cancer, cardiovascular disease and gastrointestinal pathology. There is a threshold of alcohol consumption above which the level consumed is linearly associated with adverse health outcomes. Guidelines regarding the safe level of intake vary around the world.

Context Previous research has indicated that pretreatment response expectancies of side effects often predict subsequent toxicity severity. However, this has been largely based on female patients undergoing chemotherapy. Objectives We tested whether this association also occurred in a novel cohort, men with prostate cancer undergoing radiotherapy. We investigated these associations throughout treatment (before and after side effects were medically predicted to occur), controlling known and novel variables. Methods Homogenous male patients scheduled for radiotherapy (N = 35, mean age 71 years) completed baseline (pretreatment) measures; response expectancies of 18 treatment-related side effects; questions about baseline health and hormonal treatment, emotional state, and coping style. Response expectancies of the side effects were again measured two weeks into treatment. The severity of the same 18 toxicities was assessed two and seven weeks into treatment. Results Hierarchical multiple linear regressions revealed baseline response expectancies significantly and independently predicted six of 18 toxicities two weeks into radiotherapy, contributing 12%–30% of explained variance (β = 0.39–0.59). Response expectancies assessed two weeks into treatment significantly and uniquely predicted seven of 17 experienced toxicities at seven weeks, explaining 17%–50% of variance (β = 0.49–0.91). Sexual toxicity response expectancies revealed the strongest associations with experience throughout treatment (β = 0.46–0.91), with “inability to reach orgasm” showing the largest effect. Conclusion In this older male sample, response expectancies of side effects predicted experiences throughout treatment, including the period before toxicities were medically expected. Response expectancies of sexual side effects were robust, independent predictors of subsequent toxicities across treatment, especially issues with orgasm, warranting focus in practice and future research.

In Aotearoa New Zealand, agricultural land-use intensification and decline in freshwater ecosystem integrity pose complex challenges for science and society. Despite riparian management programmes across the country, there is frustration over a lack in widespread uptake, upfront financial costs, possible loss in income, obstructive legislation and delays in ecological recovery. Thus, social, economic and institutional barriers exist when implementing and assessing agricultural freshwater restoration. Partnerships are essential to overcome such barriers by identifying and promoting co-benefits that result in amplifying individual efforts among stakeholder groups into coordinated, large-scale change. Here, we describe how initial progress by a sole farming family at the Silverstream in the Canterbury region, South Island, New Zealand, was used as a catalyst for change by the Canterbury Waterway Rehabilitation Experiment, a university-led restoration research project. Partners included farmers, researchers, government, industry, treaty partners (Indigenous rights-holders) and practitioners. Local capacity and capability was strengthened with practitioner groups, schools and the wider community. With partnerships in place, co-benefits included lowered costs involved with large-scale actions (e.g., earth moving), reduced pressure on individual farmers to undertake large-scale change (e.g., increased participation and engagement), while also legitimising the social contracts for farmers, scientists, government and industry to engage in farming and freshwater management. We describe contributions and benefits generated from the project and describe iterative actions that together built trust, leveraged and aligned opportunities. These actions were scaled from a single farm to multiple catchments nationally.

Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (ATXN3), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials. Here, we developed an immunoassay that readily detects polyQ ATXN3 proteins in human biological fluids and discriminates patients with SCA3 from healthy controls and individuals with other ataxias. We show that polyQ ATXN3 serves as a marker of target engagement in human fibroblasts, which may bode well for its use in clinical trials. Last, we identified a single-nucleotide polymorphism that strongly associates with the expanded allele, thus providing an exciting drug target to abrogate detrimental events initiated by mutant ATXN3. Gene-silencing strategies for several repeat diseases are well under way, and our results are expected to improve clinical trial preparedness for SCA3 therapies.

Introduced aquatic macrophytes can dominate small agricultural waterways in summer and autumn becoming a significant management problem. Excessive growth can clog waterways, causing drainage issues and reducing agricultural productivity while in-stream velocities are reduced and sedimentation increased. Consequently, water managers remove them by mechanical clearance, chemical spray and cutting which can be costly and have negative impacts on in-stream habitat and ecological health. We trialled three tools to reduce macrophytes: hand-weeding, weed mat and artificial shading, at a reach-scale (50 m) and larger-scale (200–400 m). Hand-weeding reduced cover in the short-term, however macrophytes recovered to pre-treatment levels within one season. Weed mat along the banks was effective at reducing emergent macrophytes, particularly Erythranthe guttata (monkey musk) and Nasturtium microphyllum (watercress). Weed mat lasted for several growing seasons and continued to be effective. Shading over the waterway using polythene markedly reduced submerged macrophytes indicating that heavy shading by riparian plantings could reduce submerged macrophytes in the longer-term. These results indicate that in the short-term, weed mat could be used to limit sprawling emergent macrophytes. In the longer-term, weed mat used in conjunction with riparian planting could provide shading so that macrophyte cover in these small waterways could be reduced and controlled.

Background/AimsAge-related cognitive decline is a pervasive problem in our aging population. To date, no pharmacological treatments to halt or reverse cognitive decline are available. Behavioral interventions, such as physical exercise and Mindfulness-Based Stress Reduction, may reduce or reverse cognitive decline, but rigorously designed randomized controlled trials are needed to test the efficacy of such interventions.MethodsHere, we describe the design of the Mindfulness, Education, and Exercise study, an 18-month randomized controlled trial that will assess the effect of two interventions—mindfulness training plus moderate-to-vigorous intensity exercise or moderate-to-vigorous intensity exercise alone—compared with a health education control group on cognitive function in older adults. An extensive battery of biobehavioral assessments will be used to understand the mechanisms of cognitive remediation, by using structural and resting state functional magnetic resonance imaging, insulin sensitivity, inflammation, and metabolic and behavioral assessments.ResultsWe provide the results from a preliminary study (n = 29) of non-randomized pilot participants who received both the exercise and Mindfulness-Based Stress Reduction interventions. We also provide details on the recruitment and baseline characteristics of the randomized controlled trial sample (n = 585).ConclusionWhen complete, the Mindfulness, Education, and Exercise study will inform the research community on the efficacy of these widely available interventions improve cognitive functioning in older adults.

CITATION: Clements, H. S., et al. 2020. Private rhino conservation : diverse strategies adopted in response to the poaching crisis. Conservation Letters, 2020:e12741, doi:10.1111/conl.12741.

Breast cancer is a common cancer among women in the US and cultural barriers and medical mistrust have been associated with breast cancer screening (BCS) rates among minority populations. A heterogeneous sample of Arab women (N = 196) were recruited from across the Detroit metropolitan area and administered a questionnaire. Multiple regression analyses revealed an association between Arab Cultural Specific Barriers (ACSB) to BCS and Group-Based Medical Mistrust Scale. The environmental ACSB to BCS was associated with the medical mistrust—suspicion of HC providers (β = 0.363, p = 0.01), lack of HC provider support (β = 0.396, p = 0.001), and Arab inequities (β = 0.250, p = 0.05). Findings suggest that ACSB to BCS are predictive of medical mistrust for Arab American women. This study illuminates the need to emphasize strategies that will target the medical care system and the cultural barriers to BCS that Arab American women face in the health care system.

Background It is not clear how the pathology, presentation and outcome for patients who present with de novo metastatic breast cancer (dnMBC) compare with those who later develop distant metastases. DnMBC is uncommon in younger patients. We describe these differences within a cohort of young patients in the United Kingdom. Methods Women aged 40 years or younger with a first invasive breast cancer were recruited to the prospective POSH national cohort study. Baseline clinicopathological data were collected, with annual follow-up. Overall survival (OS) and post-distant relapse-free survival (PDRS) were assessed using Kaplan–Meier curves. Results In total, 862 patients were diagnosed with metastatic disease. DnMBC prevalence was 2.6% (76/2977). Of those with initially localised disease, 27.1% (786/2901) subsequently developed a distant recurrence. Median follow-up was 11.00 years (95% CI 10.79–11.59). Patients who developed metastatic disease within 12 months had worse OS than dnMBC patients (HR 2.64; 1.84–3.77). For PDRS, dnMBC was better than all groups, including those who relapsed after 5 years. Of dnMBC patients, 1.3% had a gBRCA1, and 11.8% a gBRCA2 mutation. Conclusions Young women with dnMBC have better PDRS than those who develop relapsed metastatic breast cancer. A gBRCA2 mutation was overrepresented in dnMBC.

Enhanced production of dehydroepiandrosterone (DHEA) by the foetal hypothalamic-pituitary-adrenal (HPA) axis enables maturational events critical for labour induction and neonatal adaptation. Despite knowledge of the interconnected nature of maternal and foetal physiology and dramatic changes in DHEA production after birth, few studies have examined DHEA levels in newborns and none have examined DHEA's response to acute stress. Understanding normative patterns of early DHEA activity is needed to accurately assess functioning of the biological stress system with relevance for health and development. The present study analysed DHEA concentrations and change after stress among 93 newborns and associations with pregnancy, delivery and demographic risk factors. Three saliva samples, collected prior to and following a blood draw stressor, were used to determine baseline and stress reactive DHEA levels. Mothers self-reported on health behaviours during pregnancy. Data on obstetric factors were obtained from medical records. DHEA levels declined from pre- to post-stressor assessments. Results also showed that post-stressor DHEA change was significantly associated with administration of medications used to treat pain and accelerate labour. However, there was no significant variation in DHEA pre-stress levels or change after stress as a function of time after birth. By capturing DHEA levels after birth, the present study provides a window into prenatal health of the HPA system. The study also advances knowledge of DHEA in newborns by providing data on reference levels and important covariates. This information on basic adrenal physiology provides a foundation that can be expanded on to enhance understanding of early hypothalamic-pituitary-adrenal axis activity.

Sex chromosome trisomies (SCTs) (XXX, XXY, and XYY karyotypes) are associated with an elevated risk of neurodevelopmental disorders. The range of severity of the pheno- type is substantial. We considered whether this variable outcome was related to the presence of copy number variants (CNVs)—stretches of duplicated or deleted DNA. A sample of 125 children with an SCT were compared with 181 children of normal kar- yotype who had been given the same assessments. First, we compared the groups on measures of overall CNV burden: number of CNVs, total span of CNVs, and likely functional impact (probability of loss-of-function intolerance, pLI, summed over CNVs). Differences between groups were small relative to within-group variance and not sta- tistically significant on overall test. Next, we considered whether a measure of general neurodevelopmental impairment was predicted by pLI summed score, SCT versus com- parison group, or the interaction between them. There was a substantial effect of SCT/comparison status but the pLI score was not predictive of outcomes in either group. We conclude that variable presence of CNVs is not a likely explanation for the wide phenotypic variation in children with SCTs. We discuss methodological challenges of testing whether CNVs are implicated in causing neurodevelopmental problems.

Biodiversity conservation relies heavily on protected areas (PAs). However, in locations that are desirable for agriculture, industry, or human habitation (e.g., lowland habitats on fertile soils, coastal zones), land is often privately owned and state-owned PAs tend to be under-represented. Despite the potentially disproportionate contribution that privately protected areas (PPAs) could make to representing biodiversity and supporting its persistence across regional PA estates, this contribution is poorly understood. We assessed the capacity of PPAs to contribute to the persistence of 38 large- and medium-sized mammals in the Cape Floristic Region, South Africa, based on a previously published conservation plan that used species population requirements to identify areas of importance for mammal conservation. We hypothesized that, relative to state-owned PAs, PPAs would be disproportionately located in areas important to the regional persistence of the mammal assemblage, given: (a) historic biases in the distribution of private- and state-owned land across high and low productivity landscapes, respectively; (b) private landholders' recent focus on wildlife-orientated enterprises; and (c) the conservation trade-offs influencing expansions of the state-owned PA estate. As a result of the high numbers of PPAs and their bias towards areas of importance for mammal conservation, the potential mammal species diversity and richness that could persist within a PA increased more rapidly with PA size on PPAs than on state-owned PAs. These PPAs therefore have the potential to significantly increase both the regional-scale diversity of protected mammals and the number of viable populations. Furthermore, PPAs could make the greatest absolute contribution to the conservation of protected species when adjoining, and thus expanding, state-owned PAs (i.e., mixed-ownership PAs). Regional conservation targets for a quarter of the species were only met due to the inclusion of private- and/or mixed-ownership PAs in the estate. Policy implications. Our findings show that privately protected areas (PPAs) could play a substantial role in the long-term conservation of terrestrial megafauna within a multi-tenure protected area (PA) estate, due to their prevalence in high-productivity landscapes. The significant gains from augmenting state-owned PAs with PPAs emphasize the value of systematic conservation planning and implementation across tenure types.

Acute myeloid leukemia (AML) patients with FLT3/ITD mutations have a poor prognosis. Monotherapy with selective FLT3 tyrosine kinase inhibitors (TKIs) have shown transient and limited efficacy due to the development of resistance. Arsenic trioxide (ATO, As2O3) has been proven effective in treating acute promyelocytic leukemia (APL) and has shown activity in some cases of refractory and relapsed AML and other hematologic malignances. We explored the feasibility of combining FLT3 TKIs with ATO in the treatment of FLT3/ITD+ leukemias. The combination of FLT3 TKIs with ATO showed synergistic effects in reducing proliferation, viability and colony forming ability, and increased apoptosis in FLT3/ITD+ cells and primary patient samples. In contrast, no cooperativity was observed against wild-type FLT3 leukemia cells. ATO reduced expression of FLT3 RNA and its upstream transcriptional regulators (HOXA9, MEIS1), and induced poly-ubiquitination and degradation of the FLT3 protein, partly through reducing its binding with USP10. ATO also synergizes with FLT3 TKIs to inactivate FLT3 autophosphorylation and phosphorylation of its downstream signaling targets, including STAT5, AKT and ERK. Furthermore, ATO combined with sorafenib, a FLT3 TKI, in vivo reduced growth of FLT3/ITD+ leukemia cells in NSG recipients. In conclusion, these results suggest that ATO is a potential candidate to study in clinical trials in combination with FLT3 TKIs to improve the treatment of FLT3/ITD+ leukemia.

Objective Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is the most common dominantly inherited ataxia. Despite advances in understanding this CAG repeat/polyglutamine expansion disease, there are still no therapies to alter its progressive fatal course. Here, we investigate whether an antisense oligonucleotide (ASO) targeting the SCA3 disease gene, ATXN3, can prevent molecular, neuropathological, electrophysiological, and behavioral features of the disease in a mouse model of SCA3. Methods The top ATXN3-targeting ASO from an in vivo screen was injected intracerebroventricularly into early symptomatic transgenic SCA3 mice that express the full human disease gene and recapitulate key disease features. Following a single ASO treatment at 8 weeks of age, mice were evaluated longitudinally for ATXN3 suppression and rescue of disease-associated pathological changes. Mice receiving an additional repeat injection at 21 weeks were evaluated longitudinally up to 29 weeks for motor performance. Results The ATXN3-targeting ASO achieved sustained reduction of polyglutamine-expanded ATXN3 up to 8 weeks after treatment and prevented oligomeric and nuclear accumulation of ATXN3 up to at least 14 weeks after treatment. Longitudinal ASO therapy rescued motor impairment in SCA3 mice, and this rescue was associated with a recovery of defects in Purkinje neuron firing frequency and afterhyperpolarization. Interpretation This preclinical study established efficacy of ATXN3-targeted ASOs as a disease-modifying therapeutic strategy for SCA3. These results support further efforts to develop ASOs for human clinical trials in this polyglutamine disease as well as in other dominantly inherited disorders caused by toxic gain of function. Ann Neurol 2018;83:64-77.

Background: Checkpoint inhibition is a very successful treatment strategy in cancers that are naturally immunogenic by attracting T cells into the tumor microenvironment (TME) and promoting cytotoxic signaling pathways. While this strategy has shown some efficacy in metastatic breast cancer, most breast cancers are not highly immunogenic likely due to an immunosuppressive microenvironment and a lack of tumor antigen expression and recognition. One strategy to transform the breast TME is to use epigenetic modulation to affect activation and trafficking of myeloid derived suppressor cells (MDSCs), known to alter the immunogenicity of the TME and sensitize tumors to checkpoint modulation. We hypothesize that combinatorial therapy primes the TME by altering infiltration and function of MDSCs leading to a more robust T cell response. Methods: We are using a HER-2/neu transgenic mouse model with tumor challenge of syngeneic cell lines to test the efficacy of different combinations of an epigenetic agent, the histone deacetylase inhibitor entinostat (ENT), checkpoint inhibitors anti -programmed cell death protein (a-PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (a-CTLA-4) antibodies, with and without anti-HER2 antibodies. We will examine treatment effects on tumor growth, and hope to identify co-stimulatory and inhibitory factors regulating T cell and MDSC responses. Characterization of tumor infiltrating lymphocytes and their functional capabilities are being investigated in primary tumors using fluorescence-activated cell sorting, nanostring gene expression profiling, and immunohistochemistry. Results: We found significant improvement in survival and delay in tumor growth in mice treated with ENT in combination with a-PD-1 and/or a-CTLA-4. Addition of anti-HER2 therapy to ENT and a-CTLA4 or a-PD1 also significantly improves survival and delay in tumor growth. We also found addition of ENT to checkpoint inhibition leads to significantly increased infiltration of granulocytic-MDSCs into the TME. We demonstrate an increase in CD8+ T effector cells in mice treated with combination therapy. Flow cytometric evaluation of markers of T cell activation, exhaustion, and MDSC function demonstrate significantly increased T cell activation, exhaustion, and myeloid function however it is unclear how this directly effects the phenotype we have observed in these mice. Gene expression profiling of both MDSCs and lymphocytes infiltrating tumors is underway to help determine significant changes in immune related pathways that lead to our observed outcomes. Conclusions: Addition of ENT to checkpoint inhibition significantly increases infiltration of innate and adaptive immune cells into the highly tolerant neu-N breast tumors and leads to improved survival and decreased tumor burden. Functional assays are underway and future studies will further delineate changes in immune infiltration as well as genetic alterations responsible for these observations. It is our hope that these novel findings will provide further rationale for combination therapy and improve the response rate of these immune therapies in patients with breast cancer. Citation Format: Roussos Torres ET, Ma H, Christmas B, Armstrong T, Jaffee EM. Combination checkpoint inhibition and epigenetic modulation promotes tumor suppression and improves survival in Her2+ models of breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-08-01.

Background Long-term survival, risk of transplantation, and causes of death after repair of total anomalous pulmonary venous connection (TAPVC) remain unknown. By linking the Pediatric Cardiac Care Consortium with the National Death Index and the United Network for Organ Sharing, we evaluated long-term transplant-free survival in children undergoing repair of TAPVC. Methods We identified 777 infants within the Pediatric Cardiac Care Consortium who underwent TAPVC repair (median 21 days; interquartile range, 5 to 80) and had sufficient personal identifiers for linkage with the National Death Index and United Network for Organ Sharing. Sixty-six deaths, ten cardiac transplantations, and one bilateral lung transplantation had occurred by the end of 2014. Data collected included age and weight at time of procedure, TAPVC type, associated cardiac lesions, and postoperative length of stay. The study cohort was divided into simple and complex TAPVC based on the presence of an associated cardiac lesion. Parametric survival plots were constructed, and risk factor analyses were performed to identify demographic and clinical characteristics associated with long-term outcomes. Results Mortality or need for transplantation was 9.7% with a median follow-up of 18.4 years and a median age of death or transplant of 0.74 years. The risk of mortality and transplant after TAPVC repair was highest during the first 18 months after hospital discharge. Cardiac causes accounted for the majority of deaths. Multivariate regression models for transplant-free survival demonstrated that complex TAPVC, mixed TAPVC, and postoperative length of stay were associated with increased risk of death/transplant. Conclusions Transplant-free survival after TAPVC repair is excellent, with most deaths or transplant events occurring early. Factors associated with the worst long-term outcomes included complex TAPVC, mixed TAPVC, and prolonged postoperative length of stay.

The ability of private conservation organizations to remain financially viable is a key factor influencing their effectiveness. One-third of financially motivated private-land conservation areas (PLCAs) surveyed in South Africa are unprofitable, raising questions about landowners' abilities to effectively adapt their business models to the socioeconomic environment. In any complex system, options for later adaptation can be constrained by starting conditions (path dependence). We tested 3 hypothesized drivers of path dependence in PLCA ecotourism and hunting business models: (H1) the initial size of a PLCA limits the number of mammalian game and thereby predators that can be sustained; (H2) initial investments in infrastructure limit the ability to introduce predators; and (H3) rainfall limits game and predator abundance. We further assessed how managing for financial stability (optimized game stocking) or ecological sustainability (allowing game to fluctuate with environmental conditions) influenced the ability to overcome path dependence. A mechanistic PLCA model based on simple ecological and financial rules was run for different initial conditions and management strategies, simulating landowner options for adapting their business model annually. Despite attempts by simulated landowners to increase profits, adopted business models after 13 years were differentiated by initial land and infrastructural assets, supporting H1 and H2. A conservation organization's initial assets can cause it to become locked into a financially vulnerable business model. In our 50-year simulation, path dependence was overcome by fewer of the landowners who facilitated natural ecological variability than those who maintained constant hunting rates and predator numbers, but the latter experienced unsustainably high game densities in low rainfall years. Management for natural variability supported long-term ecological sustainability but not shorter term socioeconomic sustainability for PLCAs. Our findings highlight trade-offs between ecological and economic sustainability and suggest a role for governmental support of the private conservation industry.

There has been limited consideration of the dynamic interactions between ecosystem service supply and demand. For self-funded private protected areas (PPAs), managers’ abilities to provide cultural ecosystem services (CESs) for which tourists are willing to pay may be critical to their sustainability. We predicted that a PPA’s management strategy would reflect the CES preferences of its visitors. Four CES bundles were identified across 21 South African PPAs: “safari experience”, “sense of place”, “natural history”, and “recreation”. Patterns in visitor preference for these bundles were strongly aligned with patterns in PPA management attributes. Preference for safari experience was documented on large PPAs with many game species and expensive, guided activities. Sense of place PPAs were small with few game species and cheap, self-guided activities. Natural history PPAs provided guided ecotourism to high quantities of day and overnight visitors, while recreation PPAs offered consumptive activities like hunting and fishing to small numbers of overnight visitors. Through their demand for specific CESs, PPA visitors both influence and respond to the management of PPAs’ ecological and socioeconomic attributes. Dynamic interactions between the demands of users and the strategies managers adopt to meet these demands can be important drivers of ecosystem service provision.

Purpose: Financial hardship due to cancer is more common among African American than White survivors. The COVID-19 pandemic and its economic fallout have also disproportionately affected African Americans. The purpose of this study is to describe the financial and employment impacts of COVID-19 in a population of African American cancer survivors and to compare those impacts with those experienced after a cancer diagnosis. Methods: Results include survey data from 593 participants in the population-based Detroit Research on Cancer Survivors (ROCS) cohort who completed the ROCS enrollment survey and a supplemental questionnaire related to the impact of the COVID-19 pandemic on their financial wellbeing and employment. Most participants (96%) were not diagnosed with COVID-19 by the time they completed the supplement and reflect the societal impact of the pandemic rather than a personal COVID-19 diagnosis. Analyses compare reports of financial hardship (using assets, borrowing money, experiencing debt, decreases in income) and employment impacts (changes to work schedules, duties, hours, employment status) due to cancer and due to the COVID-19 pandemic. Results: A similar proportion of ROCS participants reported financial hardship (41% vs. 42%) and borrowing money (5% vs. 6%) related to the COVID pandemic and their cancer diagnosis, respectively. Fewer survivors reported borrowing money (9% vs. 17%; p

Background Reaction time to initiate upper limb movement and movement time to place hands on the landing surface may be important factors in forward fall landing and impact, contributing to injury reduction. The aim was to investigate the relationship of physical function and upper body strength to upper limb reaction and movement time in older female participants. Methods 75 female participants (72 ± 8 yrs) performed 5 arm response trials. Reaction time (signal to initiation of movement), and movement time (initial movement to contact), were collected using 3D motion capture. Additional variables were: handgrip; sit-to-stand; shoulder flexion and elbow extension strength measured by hand-held dynamometry; one-legged balance; fall risk; and physical activity scores. Prediction variables for reaction and movement time were determined in separate backward selection multiple regression analyses. Significance was set at P Findings Significant regression equations for RT (r2 = 0.08, P = 0.013) found a relationship between stronger handgrip (Beta = −0.002) and faster reaction time, accounting for 8% variance. For movement time (r2 = 0.06, P = 0.036) greater shoulder flexion strength (Beta = −0.04) was related to faster movement time, explaining 6% variance. Stronger SF strength was related to a decrease in MT by 4%. Discussion A relationship between arm strength measures and faster upper body reaction and movement time was shown, with 10–20% higher strength associated with a 5% faster response time. Even though this was a relatively weak relationship, given that strength is a modifiable component this provides a potential avenue for future intervention efforts. This in turn could have an impact on forward fall landing and potential reduction of injury risk.

Objectives. To test the effectiveness of a preclinical, telephone-based patient navigation intervention to encourage colorectal cancer (CRC) screening among older Black men. Methods. We conducted a 3-parallel-arm, randomized trial among 731 self-identified Black men recruited at barbershops between 2010 and 2013 in New York City. Participants had to be aged 50 years or older, not be up-to-date on CRC screening, have uncontrolled high blood pressure, and have a working telephone. We randomized participants to 1 of 3 groups: (1) patient navigation by a community health worker for CRC screening (PN), (2) motivational interviewing for blood pressure control by a trained counselor (MINT), or (3) both interventions (PLUS). We assessed CRC screening completion at 6-month follow-up. Results. Intent-to-treat analysis revealed that participants in the navigation interventions were significantly more likely than those in the MINT-only group to be screened for CRC during the 6-month study period (17.5% of participants in PN, 17.8% in PLUS, 8.4% in MINT; P Conclusions. Telephone-based preclinical patient navigation has the potential to be effective for older Black men. Our results indicate the importance of community-based health interventions for improving health among minority men.

Objective Communication during racially-discordant interactions is often of poor quality and may contribute to racial treatment disparities. We evaluated an intervention designed to increase patient active participation and other communication-related outcomes during interactions between Black patients and non-Black oncologists. Methods Participants were 18 non-Black medical oncologists and 114 Black patients at two cancer hospitals in Detroit, Michigan, USA. Before a clinic visit to discuss treatment, patients were randomly assigned to usual care or to one of two question prompt list (QPL) formats: booklet (QPL-Only), or booklet and communication coach (QPL-plus-Coach). Patient-oncologist interactions were video recorded. Patients reported perceptions of the intervention, oncologist communication, role in treatment decisions, and trust in the oncologist. Observers assessed interaction length, patient active participation, and oncologist communication. Results The intervention was viewed positively and did not increase interaction length. The QPL-only format increased patient active participation; the QPL-plus-Coach format decreased patient perceptions of oncologist communication. No other significant effects were found. Conclusion This QPL booklet is acceptable and increases patient active participation in racially-discordant oncology interactions. Future research should investigate whether adding physician-focused interventions might improve other outcomes. Practice implications This QPL booklet is acceptable and can improve patient active participation in racially-discordant oncology interactions.

Teachable moments (TMs) are situations with potential for promoting health behavior change. Little is known as to whether colonoscopy screening itself may serve as a TM, particularly among low-income or minority populations. Research in this area is needed to inform efforts to address the disproportionate burden of colorectal cancer (CRC) experienced by minorities. This study aims to describe attitudes related to physical activity (PA) and healthy eating among a low-income Hispanic and African American sample, assess whether colonoscopy completion may encourage changes in dietary behavior or PA, and determine the type of interventions minority participants would prefer to promote preventive behaviors. Average-risk African American and Hispanic individuals who are referred for a screening colonoscopy at a Primary Care Clinic between May 2008 and December 2011 were eligible. Data were collected at three time points: at recruitment, 2 weeks before their colonoscopy, and 1 month after their colonoscopy (n = 537). The difference in change in PA from baseline to post-colonoscopy follow-up between those who had a colonoscopy and those who did not was significant (p = .04). Those who completed a colonoscopy increased their PA by 0.26 days on average, whereas, those who did not decreased their PA by 0.46 days. Findings suggest that the time following colonoscopy completion may be ideal to provide health promotion for PA and healthy eating. Future research is needed to explore the mechanisms that influence health behavior change as a result of colonoscopies to inform the development of interventions in this area.

In managed natural resource systems, such as fisheries and rangelands, there is a recognized trade-off between managing for short-term benefits and managing for longer term resilience. Management actions that stabilize ecological attributes or processes can improve productivity in the supply of ecosystem goods and services in the short term but erode system resilience at longer time scales. For example, fire suppression in rangelands can increase grass biomass initially but ultimately result in an undesirable, shrub-dominated system. Analyses of this phenomenon have focused largely on how management actions influence slow-changing biophysical system attributes (such as vegetation composition). Data on the frequency of management actions that reduce natural ecological variation on 66 private land-conservation areas (PLCAs) in South Africa were used to investigate how management actions are influenced by manager decision-making approaches, a largely ignored part of the problem. The pathology of natural resource management was evident on some PLCAs: increased focus on revenue-generation in decision making resulted in an increased frequency of actions to stabilize short-term variation in large mammal populations, which led to increased revenues from ecotourism or hunting. On many PLCAs, these management actions corresponded with a reduced focus on ecological monitoring and an increase in overstocking of game (i.e., ungulate species) and stocking of extralimitals (i.e., game species outside their historical range). Positives in natural resource management also existed. Some managers monitored slower changing ecological attributes, which resulted in less-intensive management, fewer extralimital species, and lower stocking rates. Our unique, empirical investigation of monitoring-management relationships illustrates that management decisions informed by revenue monitoring versus ecological monitoring can have opposing consequences for natural resource productivity and sustainability. Promoting management actions that maintain resilience in natural resource systems therefore requires cognizance of why managers act the way they do and how these actions can gradually shift managers toward unsustainable strategies.

All-trans retinoic acid (ATRA) has been very successful in the subtype of acute myelogenous leukemia known as acute promyelocytic leukemia due to targeted reactivation of retinoic acid signaling. There has been great interest in applying this form of differentiation therapy to other cancers, and numerous clinical trials have been initiated. However, ATRA as monotherapy has thus far shown little benefit in nonacute promyelocytic leukemia acute myelogenous leukemia. Here, we review the literature on the use of ATRA in combination with chemotherapy, epigenetic modifying agents and targeted therapy, highlighting specific patient populations where the addition of ATRA to existing therapies may provide benefit. Furthermore, we discuss the impact of recent whole genome sequencing efforts in leading the design of rational combinatorial approaches.

BackgroundNiemann–Pick disease type C is a fatal and progressive neurodegenerative disorder characterized by the accumulation of unesterified cholesterol in late endosomes and lysosomes. We sought to develop new therapeutics for this disorder by harnessing the body’s endogenous cholesterol scavenging particle, high-density lipoprotein (HDL).MethodsHere we design, optimize, and define the mechanism of action of synthetic HDL (sHDL) nanoparticles.ResultsWe demonstrate a dose-dependent rescue of cholesterol storage that is sensitive to sHDL lipid and peptide composition, enabling the identification of compounds with a range of therapeutic potency. Peripheral administration of sHDL toNpc1 I1061Thomozygous mice mobilizes cholesterol, reduces serum bilirubin, reduces liver macrophage size, and corrects body weight deficits. Additionally, a single intraventricular injection into adultNpc1 I1061Tbrains significantly reduces cholesterol storage in Purkinje neurons. Since endogenous HDL is also a carrier of sphingomyelin, we tested the same sHDL formulation in the sphingomyelin storage disease Niemann–Pick type A. Utilizing stimulated Raman scattering microscopy to detect endogenous unlabeled lipids, we show significant rescue of Niemann–Pick type A lipid storage.ConclusionsTogether, our data establish that sHDL nanoparticles are a potential new therapeutic avenue for Niemann–Pick diseases.

Views that protected area (PA) expansion relies predominantly on land purchased by government are increasingly being challenged. The inclusion of privately owned PAs (PPAs) in national conservation strategies is now commonplace, but little is known about their long‐term persistence and how it compares to that of state‐owned PAs. We undertook the first long‐term assessment of the dynamics of a national system of terrestrial PPAs, assessing its growth, as well as its resilience to downgrading, downsizing, and degazettement (PADDD). Between 1926 and 2018, 6.2% of all private nature reserves established in South Africa were degazetted, compared to 2.2% of state‐owned nature reserves. Privately owned PA growth exceeded that of state‐owned PAs. Trends in PA establishment differed between privately owned and state‐owned PAs, reflecting different legislative, political, and economic events. Our findings highlight the value of enabling legislative environments to facilitate PPA establishment, and demonstrate the potential of PPAs as a long‐term conservation strategy.

Objective The purpose of this study was to examine the state of smartphone applications for cancer intended for the general public with a focus on interactive features, content sources, and application developer affiliations. The level of health provider involvement in screening or appraising application content was also assessed. Methods A total of 123 apps were identified for analysis from two major mobile application marketplaces (Apple iTunes = 40; Google Play = 83). Application characteristics were collected, analyzed, and reported. These included the mobile platform, cost, application developer affiliation, date of last update, purpose of application, content sources, and interactive features. Results In the study sample, 50% of the applications focused on general information for cancer (62/123). Next, this was followed by applications for breast cancer (15%, 19/123) and skin cancer (7%, 8/123). Only 10% of application descriptions (12/123) identified sources for application content. Interactive features included the ability to monitor symptoms, side effects, treatments, and chronic pain (20%, 25/123). Only 3% of the applications (4/123) stated content had been evaluated by health providers. Conclusions This study contributes an updated analysis of applications for cancer available in the digital health marketplace. The findings have implications for information quality and supportive resources for cancer care. More transparent information about content sources, organizational affiliations, and level of health provider oversight in screening application content is warranted. Recommendations for improving the quality of cancer applications are also offered.

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Background Kidney transplantation is the preferred treatment for end-stage renal failure. Unfortunately, donor organ shortages prevent many individuals receiving a renal transplant and there is a need to increase the pool of appropriate donors. The presence of acute kidney injury (AKI) in deceased donors has traditionally been a relative contraindication to renal transplantation, even though renal recovery may be favorable in the absence of chronic renal disease. Methods We undertook an 8 years retrospective observational study of potential deceased organ donors with AKI requiring renal replacement therapy (RRT). We evaluated the rate of successful transplantation as well as short term and outcomes at a median of 19.5 (13.0-52.7) months after donation. Results Amongst 1058 consented potential organ donors, 39 patients had AKI requiring RRT, of which 19 became donors (13 not medically suitable, 7 did not proceed to donation). The median (interquartile range (IQR)) donor age was 41 (34-50) years and norepinephrine, epinephrine and vasopressin were given to 18, 14 and 9 donors, respectively. From the 38 donated kidneys 34 were transplanted. The median (IQR) age of recipients was 53 (42.8-58.5) years and they were dialysis free in a median (IQR) of 5.5 (2.3-10.8) days. Only minor abnormalities were found at 3 and 6 months renal biopsies, and two patients experienced graft failure in the first 12 months. Conclusion Amongst deceased donors with AKI receiving RRT and vasoactive medications outcomes of renal transplantation seems acceptable in the absence of pre-existing renal failure and other donor co-morbidity. Such patients may be an important additional source of kidney donation.

Excessive macrophytes can cause significant problems in agricultural waterways requiring active management. Conventional control techniques can have a range of adverse effects. We investigated several control tools in two experiments: firstly, we tested eight treatments at a small-scale (2 m × 2 m). We found intensive hand weeding, weed mat and herbicide spraying to be effective treatments, reducing macrophyte cover to

eHealth is a promising resource for cancer survivors and may contribute to reducing racial disparities in cancer survivorship. This research applies the Unified Theory of Acceptance and Use of Technology (UTAUT) to examine eHealth activity among African American (AfAm) and white cancer survivors. In a population-based sample of AfAm and white survivors (n=300), a Poisson regression tested whether UTAUT constructs (facilitating conditions, social influence, perceived ease of use, perceived usefulness) and beliefs about security/trustworthiness of eHealth were associated with the number of eHealth activities respondents had used. To test whether the effects varied across racial groups, interactions between each of these five facets and survivor race were included in the model. The model adjusted for demographic characteristics, cancer history, and internet access and use. Across racial groups, facilitating conditions (IRR=1.44, 95%CI [1.17, 1.77]) and perceived usefulness (IRR=1.16, 95%CI [1.08, 1.24]) were associated with increased eHealth activity. A marginally significant interaction between race and perceived ease of use (IRR=1.17, 95%CI [0.99, 1.39]) indicated this perception was associated with decreased eHealth activity for white but not AfAm survivors. A significant interaction between race and perceived security/trustworthiness (IRR=1.16, 95%CI [1.02, 1.32]) indicated this perception was associated with increased eHealth activity for AfAm but not white survivors. Social influence was not associated with eHealth use for either group (IRR=1.07, 95%CI [0.98, 1.16]). Interventions targeting attitudes about eHealth may encourage its adoption and use. Furthermore, eHealth tools intended for use among AfAm cancer survivors should ensure they are secure and emphasize trustworthiness to intended users.

Myeloproliferative neoplasms (MPN) are a phenotypically defined, heterogeneous group of blood cancers characterised by the proliferation of progenitor cells and the accumulation of mature myeloid cells, linked by a propensity to transform into myelofibrosis or acute myeloid leukaemia. The Jak2V617F

This study assessed psychological morbidity and resilience, including the subjective burden of 76 caregivers of elderly cancer survivors utilizing a cross-sectional questionnaire. Participants were mainly elderly female spouses, sole-caregiving > 35 hours per week; 19.1% and 23.6% reported moderate or greater anxiety and depression, respectively. A significant regression model found depression, emotion-focused coping, and greater years since diagnosis as significant predictors of subjective caregiver burden. Thus, caregiving appears a dominant role for this group and the Brief Assessment Scale for Caregivers of the Medically Ill (BASC) appears to be an efficient screening tool for psychological morbidity in this under-supported group. Refereed/Peer-reviewed

12129 Background: COVID-19 has had profound direct and indirect effects on population health to date and long-term effects are anticipated. Vulnerabilities to the most serious consequences of infection include older age, obesity, African American race and the presence of comorbid conditions. African American cancer survivors represent a particularly high-risk group, therefore understanding the impact of the virus and our strategies to prevent its spread on this patient population is important. Methods: The Detroit Research on Cancer Survivors (ROCS) cohort is a unique effort to understand the determinants of poor outcomes in African American cancer survivors. Eligible participants were diagnosed with breast, prostate, colorectal, or lung cancer on or after 1/1/2013, or with endometrial or any other cancer before age 50 on or after 01/01/2016 and were identified through the Metropolitan Detroit Cancer Surveillance System cancer registry. To date, we have enrolled 4173 survivors. Full participation includes completion of a baseline survey, and collection of biospecimens, medical records and tumor tissue, if available. Participants are also followed annually for outcomes and changes in history. A supplemental survey focused on the impact of COVID-19 was offered to enrolled participants beginning in the spring of 2020. The results presented here include data from 890 survivors who also completed the ROCS COVID survey. Results: Nearly all ( > 99%) survivors reported some change in their daily activities in an effort to reduce the risk of infection. At the time of survey, just over 1/3 of participants reported being tested for the virus and among those, 12% reported positive results. More than 40% of survivors reported some disruption in their access to medical care. A substantial ( > 40%) proportion of survivors reported feeling anxious, depressed and/or isolated during the COVID-19 pandemic. Approximately 40% of patients reported changes in health behaviors as a direct result of the pandemic that are known to negatively affect survivorship outcomes (physical inactivity, smoking, alcohol use). Notably, 30% of survivors reported declines in physical activity and these declines were significantly associated with increased anxiety (p = 0.008), depression (p = 0.005) and poorer health-related quality of life (p < 0.001). Conclusions: The influence of the COVID-19 pandemic on African American cancer survivors has been substantial, affecting both their physical and mental health and access to needed medical care. Coupled with changes in health behaviors as a direct result of the pandemic, these factors will likely affect outcomes in this high-risk patient population making further study and interventions necessary to mitigate the long-term impact of the pandemic on cancer outcomes.