Tolerability of Induction Chemotherapy Dosing Practices in Acute Myeloid Leukemia Patients

For patients with high body surface areas (BSA), differing chemotherapy dosing strategies have been utilized in attempts to reduce toxicity. In a retrospective evaluation, we compared the effects of chemotherapy dosing in acute myeloid leukemia patients with high BSA (\u3e2 m2) who received capped doses (n = 12) to those who received uncapped doses (n = 24), and to patients with BSA ≤ 2 m2 (n = 42). There were no statistically significant differences among groups (BSA ≤ 2 m2, BSA \u3e 2 m2 capped, and BSA \u3e 2 m2 uncapped) in the incidences of febrile neutropenia (85.7, 66.7, and 75.0%, respectively, p = 0.29), bacteremia (19.0, 8.3, and 16.7%, respectively, p = 0.68), mucositis (42.8, 50.0, and 41.7%, respectively, p = 0.88) or nausea/vomiting (47.6, 33.3, and 37.5, respectively, p = 0.57). Results suggest delivery of unadjusted chemotherapy based on actual body weight is likely safe in hematological malignancies

Dual Mission Scenarios for the Human Lunar Campaign - Performance, Cost and Risk Benefits

Scenarios for human lunar operations with capabilities significantly beyond Constellation Program baseline missions are potentially feasible based on the concept of dual, sequential missions utilizing a common crew and a single Ares I/CEV (Crew Exploration Vehicle). For example, scenarios possible within the scope of baseline technology planning include outpost-based sortie missions and dual sortie missions. Top level cost benefits of these dual sortie scenarios may be estimated by comparison to the Constellation Program reference two-mission-per-year lunar campaign. The primary cost benefit is the accomplishment of Mission B with a "single launch solution" since no Ares I launch is required. Cumulative risk to the crew is lowered since crew exposure to launch risks and Earth return risks are reduced versus comparable Constellation Program reference two-mission-per-year scenarios. Payload-to-the-lunar-surface capability is substantially increased in the Mission B sortie as a result of additional propellant available for Lunar Lander #2 descent. This additional propellant is a result of EDS #2 transferring a smaller stack through trans-lunar injection and using remaining propellant to perform a portion of the lunar orbit insertion (LOI) maneuver. This paper describes these dual mission concepts, including cost, risk and performance benefits per lunar sortie site, and provides an initial feasibility assessment

Withdrawing performance indicators: retrospective analysis of general practice performance under UK Quality and Outcomes Framework

Objectives To investigate the effect of withdrawing incentives on recorded quality of care, in the context of the UK Quality and Outcomes Framework pay for performance scheme. Design Retrospective longitudinal study. Setting Data for 644 general practices, from 2004/05 to 2011/12, extracted from the Clinical Practice Research Datalink. Participants All patients registered with any of the practices over the study period—13 772 992 in total. Intervention Removal of financial incentives for aspects of care for patients with asthma, coronary heart disease, diabetes, stroke, and psychosis. Main outcome measures Performance on eight clinical quality indicators withdrawn from a national incentive scheme: influenza immunisation (asthma) and lithium treatment monitoring (psychosis), removed in April 2006; blood pressure monitoring (coronary heart disease, diabetes, stroke), cholesterol concentration monitoring (coronary heart disease, diabetes), and blood glucose monitoring (diabetes), removed in April 2011. Multilevel mixed effects multiple linear regression models were used to quantify the effect of incentive withdrawal. Results Mean levels of performance were generally stable after the removal of the incentives, in both the short and long term. For the two indicators removed in April 2006, levels in 2011/12 were very close to 2005/06 levels, although a small but statistically significant drop was estimated for influenza immunisation. For five of the six indicators withdrawn from April 2011, no significant effect on performance was seen following removal and differences between predicted and observed scores were small. Performance on related outcome indicators retained in the scheme (such as blood pressure control) was generally unaffected. Conclusions Following the removal of incentives, levels of performance across a range of clinical activities generally remained stable. This indicates that health benefits from incentive schemes can potentially be increased by periodically replacing existing indicators with new indicators relating to alternative aspects of care. However, all aspects of care investigated remained indirectly or partly incentivised in other indicators, and further work is needed to assess the generalisability of the findings when incentives are fully withdrawn

Understanding the Lunar System Architecture Design Space

Based on the flexible path strategy and the desire of the international community, the lunar surface remains a destination for future human exploration. This paper explores options within the lunar system architecture design space, identifying performance requirements placed on the propulsive system that performs Earth departure within that architecture based on existing and/or near-term capabilities. The lander crew module and ascent stage propellant mass fraction are primary drivers for feasibility in multiple lander configurations. As the aggregation location moves further out of the lunar gravity well, the lunar lander is required to perform larger burns, increasing the sensitivity to these two factors. Adding an orbit transfer stage to a two-stage lunar lander and using a large storable stage for braking with a one-stage lunar lander enable higher aggregation locations than Low Lunar Orbit. Finally, while using larger vehicles enables a larger feasible design space, there are still feasible scenarios that use three launches of smaller vehicles

Discrete Element Method Simulation of a Boulder Extraction From an Asteroid

The force required to pull 7t and 40t polyhedral boulders from the surface of an asteroid is simulated using the discrete element method considering the effects of microgravity, regolith cohesion and boulder acceleration. The connection between particle surface energy and regolith cohesion is estimated by simulating a cohesion sample tearing test. An optimal constant acceleration is found where the peak net force from inertia and cohesion is a minimum. Peak pulling forces can be further reduced by using linear and quadratic acceleration functions with up to a 40% reduction in force for quadratic acceleration

Feasibility and acceptability of telehealth coaching to promote healthy eating in chronic kidney disease: A mixed-methods process evaluation

Objective To evaluate the feasibility and acceptability of a personalised telehealth intervention to support dietary self-management in adults with stage 3-4 chronic kidney disease (CKD). Design Mixed-methods process evaluation embedded in a randomised controlled trial. Participants People with stage 3-4 CKD (estimated glomerular filtration rate [eGFR]15-60 mL/min/1.73 m 2). Setting Participants were recruited from three hospitals in Australia and completed the intervention in ambulatory community settings. Intervention The intervention group received one telephone call per fortnight and 2-8 tailored text messages for 3 months, and then 4-12 tailored text messages for 3 months without telephone calls. The control group received usual care for 3 months then non-tailored education-only text messages for 3 months. Main outcome measures Feasibility (recruitment, non-participation and retention rates, intervention fidelity and participant adherence) and acceptability (questionnaire and semistructured interviews). Statistical analyses performed Descriptive statistics and qualitative content analysis. Results Overall, 80/230 (35%) eligible patients who were approached consented to participate (mean±SD age 61.5±12.6 years). Retention was 93% and 98% in the intervention and control groups, respectively, and 96% of all planned intervention calls were completed. All participants in the intervention arm identified the tailored text messages as useful in supporting dietary self-management. In the control group, 27 (69%) reported the non-tailored text messages were useful in supporting change. Intervention group participants reported that the telehealth programme delivery methods were practical and able to be integrated into their lifestyle. Participants viewed the intervention as an acceptable, personalised alternative to face-face clinic consultations, and were satisfied with the frequency of contact. Conclusions This telehealth-delivered dietary coaching programme is an acceptable intervention which appears feasible for supporting dietary self-management in stage 3-4 CKD. A larger-scale randomised controlled trial is needed to evaluate the efficacy of the coaching programme on clinical and patient-reported outcomes. Trial registration number ACTRN12616001212448; Results

Clumped isotopologue constraints on the origin of methane at seafloor hot springs

Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 223 (2018): 141-158, doi:10.1016/j.gca.2017.11.030.Hot-spring fluids emanating from deep-sea vents hosted in unsedimented ultramafic and mafic rock commonly contain high concentrations of methane. Multiple hypotheses have been proposed for the origin(s) of this methane, ranging from synthesis via reduction of aqueous inorganic carbon (ΣCO2) during active fluid circulation to leaching of methane-rich fluid inclusions from plutonic rocks of the oceanic crust. To further resolve the process(es) responsible for methane generation in these systems, we determined the relative abundances of several methane isotopologues (including 13CH3D, a “clumped” isotopologue containing two rare isotope substitutions) in hot-spring source fluids sampled from four geochemically-distinct hydrothermal vent fields (Rainbow, Von Damm, Lost City, and Lucky Strike). Apparent equilibrium temperatures retrieved from methane clumped isotopologue analyses average 310−42 +53 °C, with no apparent relation to the wide range of fluid temperatures (96 to 370 °C) and chemical compositions (pH, [H2], [ΣCO2], [CH4]) represented. Combined with very similar bulk stable isotope ratios (13C/12C and D/H) of methane across the suite of hydrothermal fluids, all available geochemical and isotopic data suggest a common mechanism of methane generation at depth that is disconnected from active fluid circulation. Attainment of equilibrium amongst methane isotopologues at temperatures of ca. 270 to 360 °C is compatible with the thermodynamically-favorable reduction of CO2 to CH4 at temperatures at or below ca. 400 °C under redox conditions characterizing intrusive rocks derived from sub-ridge melts. Collectively, the observations support a model where methane-rich aqueous fluids, known to be trapped in rocks of the oceanic lithosphere, are liberated from host rocks during hydrothermal circulation and perhaps represent the major source of methane venting with thermal waters at unsedimented hydrothermal fields. The results also provide further evidence that water-rock reactions occurring at temperatures lower than 200 °C do not contribute significantly to the quantities of methane venting at mid-ocean ridge hot springs.Financial support from the U.S. National Science Foundation (NSF awards EAR-1250394 to S.O., and OCE-1061863 and OCE-0549829 to J.S.S.), the National Aeronautics and Space Administration (NASA) (NNX-327 09AB75G to J.S.S., and the NASA Astrobiology Institute “Rock- Powered Life” project under cooperative agreement NNA15BB02A to S.O.), the Alfred P. Sloan Foundation via the Deep Carbon Observatory (to S.O. and J.S.S.), the U.S. Department of Defense (DoD) through a National Defense Science & Engineering Graduate (NDSEG) Fellowship (to D.T.W.), a Shell-MIT Energy Initiative Fellowship, and the Kerr-McGee Professorship at MIT (to S.O.) is gratefully acknowledged