Acupressure to Reduce Treatment-Related Symptoms for Children With Cancer and Recipients of Hematopoietic Stem Cell Transplant: Protocol for a Randomized Controlled Trial.

BackgroundWe describe the study design and protocol of a pragmatic randomized controlled trial (RCT) Acupressure for Children in Treatment for a Childhood Cancer (ACT-CC).ObjectiveTo describe the feasibility and effectiveness of an acupressure intervention to decrease treatment-related symptoms in children in treatment for cancer or recipients of a chemotherapy-based hematopoietic stem cell transplant (HSCT).DesignTwo-armed RCTs with enrollment of 5 to 30 study days.SettingTwo pediatric teaching hospitals.PatientsEighty-five children receiving cancer treatment or a chemotherapy-based HSCT each with 1 parent or caregiver.InterventionPatients are randomized 1:1 to receive either usual care plus daily professional acupressure and caregiver delivered acupressure versus usual care alone for symptom management. Participants receive up to 20 professional treatments.Main outcomeA composite nausea/vomiting measure for the child.Secondary outcomesChild's nausea, vomiting, pain, fatigue, depression, anxiety, and positive affect.Parent outcomesDepression, anxiety, posttraumatic stress symptoms, caregiver self-efficacy, and positive affect. Feasibility of delivering the semistandardized intervention will be described. Linear mixed models will be used to compare outcomes between arms in children and parents, allowing for variability in diagnosis, treatment, and age.DiscussionTrial results could help childhood cancer and HSCT treatment centers decide about the regular inclusion of trained acupressure providers to support symptom management

Mortality in Levodopa-Treated Parkinson\u27s Disease

Parkinson’s disease (PD) is associated with increased mortality despite many advances in treatment. Following the introduction of levodopa in the late 1960’s, many studies reported improved or normalized mortality rates in PD. Despite the remarkable symptomatic benefits provided by levodopa, multiple recent studies have demonstrated that PD patients continue to die at a rate in excess of their peers. We undertook this retrospective study of 211 deceased PD patients to determine the factors associated with mortality in levodopa-treated PD. Our findings confirm that PD is associated with increased mortality in both men and women. Unlike the majority of other mortality studies, we found that women have a greater reduction in lifespan compared to men. We also found that patients with early onset PD (onset at the age of 50 or before) have reduced survival relative to PD patients with later ages of onset. A final important finding is that survival is equal in PD patients treated with levodopa early (within 2 years or less of PD onset) versus later

High-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines.

Head and neck squamous cell carcinoma (HNSCC) is a common cancer diagnosis worldwide. Despite advances in treatment, HNSCC has very poor survival outcomes, emphasizing an ongoing need for development of improved therapeutic options. The distinct tumor characteristics of human papillomavirus (HPV)-positive vs. HPV-negative disease necessitate development of treatment strategies tailored to tumor HPV-status. High-throughput robotic screening of 1,433 biologically and pharmacologically relevant compounds at a single dose (4 μM) was carried out against 6 HPV-positive and 20 HPV-negative HNSCC cell lines for preliminary identification of therapeutically relevant compounds. Statistical analysis was further carried out to differentiate compounds with preferential activity against cell lines stratified by the HPV-status. These analyses yielded 57 compounds with higher activity in HPV-negative cell lines, and 34 with higher-activity in HPV-positive ones. Multi-point dose-response curves were generated for six of these compounds (Ryuvidine, MK-1775, SNS-032, Flavopiridol, AZD-7762 and ARP-101), confirming Ryuvidine to have preferential potency against HPV-negative cell lines, and MK-1775 to have preferential potency against HPV-positive cell lines. These data comprise a valuable resource for further investigation of compounds with therapeutic potential in the HNSCC

Repurposing Albendazole: new potential as a chemotherapeutic agent with preferential activity against HPV-negative head and neck squamous cell cancer.

Albendazole is an anti-helminthic drug that has been shown to exhibit anti-cancer properties, however its activity in head and neck squamous cell cancer (HNSCC) was unknown. Using a series of in vitro assays, we assessed the ability of albendazole to inhibit proliferation in 20 HNSCC cell lines across a range of albendazole doses (1 nM-10 μM). Cell lines that responded to treatment were further examined for cell death, inhibition of migration and cell cycle arrest. Thirteen of fourteen human papillomavirus-negative HNSCC cell lines responded to albendazole, with an average IC50 of 152 nM. In contrast, only 3 of 6 human papillomavirus-positive HNSCC cell lines responded. Albendazole treatment resulted in apoptosis, inhibition of cell migration, cell cycle arrest in the G2/M phase and altered tubulin distribution. Normal control cells were not measurably affected by any dose tested. This study indicates that albendazole acts to inhibit the proliferation of human papillomavirus-negative HNSCC cell lines and thus warrants further study as a potential chemotherapeutic agent for patients suffering from head and neck cancer

Examining exercise dependence symptomatology from a self-determination perspective

Background: Based on the theoretical propositions of Self-Determination Theory (SDT; Deci & Ryan, 1985) this study examined whether individuals classified as “nondependent-symptomatic” and “nondependent-asymptomatic” for exercise dependence differed in terms of the level of exercise-related psychological need satisfaction and self-determined versus controlling motivation they reported. Further, we examined if the type of motivational regulations predicting exercise behaviour differed among these groups. Methods: Participants (N = 339), recruited from fitness, community, and retail settings, completed measures of exercise-specific psychological need satisfaction, motivational regulations, exercise behaviour and exercise dependence. Results: Individuals who were nondependent-symptomatic for exercise dependence reported higher levels of competence need satisfaction and all forms of motivational regulation, compared to nondependent-asymptomatic individuals. Introjected regulation approached significance as a positive predictor of strenuous exercise behaviour for symptomatic individuals. Identified regulation was a positive predictor of strenuous exercise for asymptomatic individuals. Conclusions: The findings reinforce the applicability of SDT to understanding engagement in exercise

Origin and segregation of the human germline

Acknowledgements This work was supported by the Wellcome Investigator Awards in Science (2094)75/Z/17/Z (to MA Surani), the Wellcome Investigator Awards in Science 096738/Z/11/Z (to MA Surani), the BBSRC research grant G103986 (to MA Surani), the Croucher Postdoctoral Research Fellowship (to WWC Tang), the Wellcome 4-Yr PhD Programme in Stem Cell Biology & Medicine (2038)31/Z/16/Z (to A Castillo-Venzor) and the Cambridge Commonwealth European and International Trust (to A Castillo-Venzor), the Isaac Newton Trust (to WWC Tang), the Butterfield Awards of Great Britain Sasakawa Foundation (to T Kobayashi and MA Surani), and the Astellas Foundation for Research on Metabolic Disorders (to T Kobayashi). The marmoset embryo research is generously supported by the Wellcome Trust (WT RG89228, WT RG9242), the Centre for Trophoblast Research, the Isaac Newton Trust, and JSPS KAKENHI 15H02360, 19H05759. TE Boroviak was supported by a Wellcome Sir Henry Dale Fellowship. JC Marioni acknowledges core support from EMBL and from Cancer Research UK (C9545/A29580), which supports MD Morgan. We would like to thank Roger Barker and Xiaoling He for providing human embryonic tissues and Charles Bradshaw for bioinformatics support. We also thank The Weizmann Institute of Science for the WIS2 human PSC line and the Genomics Core Facility of CRUK Cambridge Institute for sequencing services. We thank members of the Surani laboratory for insightful comments and critical reading of the manuscript.Peer reviewedPublisher PD

Functional Performance of an Enabling Atmosphere Revitalization Subsystem Architecture for Deep Space Exploration Missions

A subsystem architecture derived from the International Space Station's (ISS) Atmosphere Revitalization Subsystem (ARS) has been functionally demonstrated. This ISS-derived architecture features re-arranged unit operations for trace contaminant control and carbon dioxide removal functions, a methane purification component as a precursor to enhance resource recovery over ISS capability, operational modifications to a water electrolysis-based oxygen generation assembly, and an alternative major atmospheric constituent monitoring concept. Results from this functional demonstration are summarized and compared to the performance observed during ground-based testing conducted on an ISS-like subsystem architecture. Considerations for further subsystem architecture and process technology development are discussed

Evaluation of an Atmosphere Revitalization Subsystem for Deep Space Exploration Missions

An Atmosphere Revitalization Subsystem (ARS) suitable for deployment aboard deep space exploration mission vehicles has been developed and functionally demonstrated. This modified ARS process design architecture was derived from the International Space Station's (ISS) basic ARS. Primary functions considered in the architecture include trace contaminant control, carbon dioxide removal, carbon dioxide reduction, and oxygen generation. Candidate environmental monitoring instruments were also evaluated. The process architecture rearranges unit operations and employs equipment operational changes to reduce mass, simplify, and improve the functional performance for trace contaminant control, carbon dioxide removal, and oxygen generation. Results from integrated functional demonstration are summarized and compared to the performance observed during previous testing conducted on an ISS-like subsystem architecture and a similarly evolved process architecture. Considerations for further subsystem architecture and process technology development are discussed

Ecosystem Stewardship: Sustainability Strategies for a Rapidly Changing Planet

Ecosystem stewardship is an action-oriented framework intended to foster social-ecological sustainability of a rapidly changing planet. Recent developments identify three strategies that make optimal use of current understanding in an environment of inevitable uncertainty and abrupt change: reducing the magnitude of, and exposure and sensitivity to, known stresses; focusing on proactive policies that shape change; and avoiding or escaping unsustainable social-ecological traps. All social-ecological systems are vulnerable to recent and projected changes but have sources of adaptive capacity and resilience that can sustain ecosystem services and human well-being through active ecosystem stewardship

School-based physical activity intervention for older adolescents: rationale and study protocol for the Burn 2 Learn cluster randomised controlled trial

Introduction This trial aims to investigate the impact of a school-based physical activity programme, involving high-intensity interval training (HIIT), on the physical, mental and cognitive health of senior school students. Methods and analysis The Burn 2 Learn (B2L) intervention will be evaluated using a two-arm parallel group cluster randomised controlled trial with allocation occurring at the school level (to treatment or wait-list control). Schools will be recruited in two cohorts from New South Wales, Australia. The trial will aim to recruit ∼720 senior school students (aged 16-18 years) from 20 secondary schools (ie, 10 schools per cohort). A range of implementation strategies will be provided to teachers (eg, training, equipment and support) to facilitate the delivery of HIIT sessions during scheduled classes. In phase I and II (3 months each), teachers will facilitate the delivery of at least two HIIT sessions/week during lesson-time. In phase III (6 months), students will be encouraged to complete sessions outside of lesson-time (teachers may continue to facilitate the delivery of B2L sessions during lesson-time). Study outcomes will be assessed at baseline, 6 months (primary end point) and 12 months. Cardiorespiratory fitness (shuttle run test) is the primary outcome. Secondary outcomes include: vigorous physical activity, muscular fitness, cognition and mental health. A subsample of students will (i) provide hair samples to determine their accumulated exposure to stressful events and (ii) undergo multimodal MRI to examine brain structure and function. A process evaluation will be conducted (ie, recruitment, retention, attendance and programme satisfaction)