Small Launch Vehicle Design Approaches: Clustered Cores Compared with Multi-Stage Inline Concepts

In an effort to better define small launch vehicle design options two approaches were investigated from the small launch vehicle trade space. The primary focus was to evaluate a clustered common core design against a purpose built inline vehicle. Both designs focused on liquid oxygen (LOX) and rocket propellant grade kerosene (RP-1) stages with the terminal stage later evaluated as a LOX/methane (CH4) stage. A series of performance optimization runs were done in order to minimize gross liftoff weight (GLOW) including alternative thrust levels, delivery altitude for payload, vehicle length to diameter ratio, alternative engine feed systems, re-evaluation of mass growth allowances, passive versus active guidance systems, and rail and tower launch methods. Additionally manufacturability, cost, and operations also play a large role in the benefits and detriments for each design. Presented here is the Advanced Concepts Office's Earth to Orbit Launch Team methodology and high level discussion of the performance trades and trends of both small launch vehicle solutions along with design philosophies that shaped both concepts. Without putting forth a decree stating one approach is better than the other; this discussion is meant to educate the community at large and let the reader determine which architecture is truly the most economical; since each path has such a unique set of limitations and potential payoffs

A Comparison of Tandem Walk Performance Between Bed Rest Subjects and Astronauts

Astronauts experience a microgravity environment during spaceflight, which results in a central reinterpretation of both vestibular and body axial-loading information by the sensorimotor system. Subjects in bed rest studies lie at 6deg head-down in strict bed rest to simulate the fluid shift and gravity-unloading of the microgravity environment. However, bed rest subjects still sense gravity in the vestibular organs. Therefore, bed rest isolates the axial-unloading component, thus allowing for the direct study of its effects. The Tandem Walk is a standard sensorimotor test of dynamic postural stability. In a previous abstract, we compared performance on a Tandem Walk test between bed rest control subjects, and short- and long-duration astronauts both before and after flight/bed rest using a composite index of performance, called the Tandem Walk Parameter (TWP), that takes into account speed, accuracy, and balance control. This new study extends the previous data set to include bed rest subjects who performed exercise countermeasures. The purpose of this study was to compare performance during the Tandem Walk test between bed rest subjects (with and without exercise), short-duration (Space Shuttle) crewmembers, and long-duration International Space Station (ISS) crewmembers at various time points during their recovery from bed rest or spaceflight

Pilot randomized trial of an electronic symptom monitoring and reporting intervention for hospitalized adults undergoing hematopoietic stem cell transplantation

Purpose: Patients undergoing a hematopoietic stem cell transplantation (HCT) have varied symptoms during their hospitalization. This study examined whether daily symptom reporting (with electronic patient-reported outcomes [PROs]) in an inpatient bone marrow transplant clinic reduced symptom burden on post-transplant days +7, +10, and +14. Methods: A prospective, single-institution1:1 pilot randomized, two-arm study recruited HCT patients. HCT inpatients (N=76) reported daily on 16 common symptoms using the PRO version of the Common Terminology for Adverse Events (PRO-CTCAE). Fisher’s exact test was used to examine differences in the proportion of patients reporting individual symptoms. Multivariable linear regression modeling was used to examine group differences in peak symptom burden, while controlling for symptom burden at baseline, age, comorbidity, and transplantation type (autologous or allogeneic). Results: HCT patients receiving the PRO intervention also experienced lower peak symptom burden (average of 16 symptoms) at days +7, +10, and +14 (10.4 vs 14.5, p =0.03). Conclusions: Daily use of electronic symptom reporting to nurses in an inpatient bone marrow transplant clinic reduced peak symptom burden and improved individual symptoms during the two weeks post-transplant. A multi-site site trial is warranted to demonstrate the generalizability, efficacy, and value of this intervention

Examining the relationship between trauma, PTSD and psychosis in patients in a UK secondary care service

Objective: Traumatic experiences and post‐traumatic stress disorder (PTSD) are common in schizophrenia. However, few studies screening for PTSD have established the temporality of PTSD‐related traumatic events to psychosis onset. Furthermore, it is unclear how many patients attribute a trauma‐based contribution to their psychosis or would find trauma‐focused therapy acceptable. We examine the prevalence and timing of trauma in psychosis, as well as patient views on the relationship between their trauma experiences and mental health difficulties, and on receiving trauma‐focused therapy. Methods: Sixty‐eight patients with an at‐risk mental state (ARMS) or psychotic disorder in a UK secondary‐care setting completed self‐report measures of trauma and PTSD, and undertook research interviews. Proportions and odds ratios were derived with 95% confidence intervals. Results: We recruited 68 participants (estimated response rate 62%; psychotic disorder n = 61, ARMS n = 7). Sixty three (95%) reported traumatic events and 32 (47%) reported childhood abuse. Twenty‐six individuals (38%) met criteria for PTSD, though for >95% this was not recorded in their notes, and 25 (37%) had sub‐threshold PTSD. For 69% of participants, their worst trauma occurred before the onset of their psychosis symptoms. Most (65%) believed their psychosis symptoms were related to past traumas and 82% of these were interested in receiving trauma‐focused therapy. Conclusions: PTSD is common in and often pre‐dates onset of psychosis. Most patients believe their symptoms and traumas are related and would be interested in trauma‐focused therapy if available. Studies evaluating the effectiveness of trauma‐focused therapies for those with or at high‐risk of psychosis are required

Clinical Opportunities for Germline Pharmacogenetics and Management of Drug-Drug Interactions in Patients With Advanced Solid Cancers.

PURPOSE: Precision medicine approaches, including germline pharmacogenetics (PGx) and management of drug-drug interactions (DDIs), are likely to benefit patients with advanced cancer who are frequently prescribed multiple concomitant medications to treat cancer and associated conditions. Our objective was to assess the potential opportunities for PGx and DDI management within a cohort of adults with advanced cancer. METHODS: Medication data were collected from the electronic health records for 481 subjects since their first cancer diagnosis. All subjects were genotyped for variants with clinically actionable recommendations in Clinical Pharmacogenetics Implementation Consortium guidelines for 13 pharmacogenes. DDIs were defined as concomitant prescription of strong inhibitors or inducers with sensitive substrates of the same drug-metabolizing enzyme and were assessed for six major cytochrome P450 (CYP) enzymes. RESULTS: Approximately 60% of subjects were prescribed at least one medication with Clinical Pharmacogenetics Implementation Consortium recommendations, and approximately 14% of subjects had an instance for actionable PGx, defined as a prescription for a drug in a subject with an actionable genotype. The overall subject-level prevalence of DDIs and serious DDIs were 50.3% and 34.8%, respectively. Serious DDIs were most common for CYP3A, CYP2D6, and CYP2C19, occurring in 24.9%, 16.8%, and 11.7% of subjects, respectively. When assessing PGx and DDIs together, approximately 40% of subjects had at least one opportunity for a precision medicine-based intervention and approximately 98% of subjects had an actionable phenotype for at least one CYP enzyme. CONCLUSION: Our findings demonstrate numerous clinical opportunities for germline PGx and DDI management in adults with advanced cancer

The importance of population differences: Influence of individual characteristics on the Australian public’s preferences for emergency care

A better understanding of the public’s preferences and what factors influence them is required if they are to be used to drive decision-making in health. This is particularly the case for service areas undergoing continual reform such as emergency and primary care. Accordingly, this study sought to determine if attitudes, socio-demographic characteristics and healthcare experiences influence the public’s intentions to access care and their preferences for hypothetical emergency care alternatives. A discrete choice experiment was used to elicit the preferences of Australian adults (n = 1529). Mixed logit regression analyses revealed the influence of a range of individual characteristics on preferences and service uptake choices across three different presenting scenarios. Age was associated with service uptake choices in all contexts, whilst the impact of other sociodemographics, health experience and attitudinal factors varied by context. The improvements in explanatory power observed from including these factors in the models highlight the need to further clarify their influence with larger populations and other presenting contexts, and to identify other determinants of preference heterogeneity. The results suggest social marketing programs undertaken as part of demand management efforts need to be better targeted if decision-makers are seeking to increase community acceptance of emerging service models and alternatives. Other implications for health policy, service planning and research, including for workforce planning and the possible introduction of a system of co-payments are discussed

Agreement between physicians and non-physician clinicians in starting antiretroviral therapy in rural Uganda

<p>Abstract</p> <p>Background</p> <p>The scarcity of physicians in sub-Saharan Africa – particularly in rural clinics staffed only by non-physician health workers – is constraining access to HIV treatment, as only they are legally allowed to start antiretroviral therapy in the HIV-positive patient. Here we present a pilot study from Uganda assessing agreement between non-physician clinicians (nurses and clinical officers) and physicians in their decisions as to whether to start therapy.</p> <p>Methods</p> <p>We conducted the study at 12 government antiretroviral therapy sites in three regions of Uganda, all of which had staff trained in delivery of antiretroviral therapy using the WHO Integrated Management of Adult and Adolescent Illness guidelines for chronic HIV care. We collected seven key variables to measure patient assessment and the decision as to whether to start antiretroviral therapy, the primary variable of interest being the Final Antiretroviral Therapy Recommendation. Patients saw either a clinical officer or nurse first, and then were screened identically by a blinded physician during the same clinic visit. We measured inter-rater agreement between the decisions of the non-physician health workers and physicians in the antiretroviral therapy assessment variables using simple and weighted Kappa analysis.</p> <p>Results</p> <p>Two hundred fifty-four patients were seen by a nurse and physician, while 267 were seen by a clinical officer and physician. The majority (> 50%) in each arm of the study were in World Health Organization Clinical Stages I and II and therefore not currently eligible for antiretroviral therapy according to national antiretroviral therapy guidelines. Nurses and clinical officers both showed moderate to almost perfect agreement with physicians in their Final Antiretroviral Therapy Recommendation (unweighted κ = 0.59 and κ = 0.91, respectively). Agreement was also substantial for nurses versus physicians for assigning World Health Organization Clinical Stage (weighted κ = 0.65), but moderate for clinical officers versus physicians (κ = 0.44).</p> <p>Conclusion</p> <p>Both nurses and clinical officers demonstrated strong agreement with physicians in deciding whether to initiate antiretroviral therapy in the HIV patient. This could lead to immediate benefits with respect to antiretroviral therapy scale-up and decentralization to rural areas in Uganda, as non-physician clinicians – particularly clinical officers – demonstrated the capacity to make correct clinical decisions to start antiretroviral therapy. These preliminary data warrant more detailed and multicountry investigation into decision-making of non-physician clinicians in the management of HIV disease with antiretroviral therapy, and should lead policy-makers to more carefully explore task-shifting as a shorter-term response to addressing the human resource crisis in HIV care and treatment.</p

Robot Assisted Training for the Upper Limb after Stroke (RATULS): study protocol for a randomised controlled trial.

BACKGROUND: Loss of arm function is a common and distressing consequence of stroke. We describe the protocol for a pragmatic, multicentre randomised controlled trial to determine whether robot-assisted training improves upper limb function following stroke. METHODS/DESIGN: Study design: a pragmatic, three-arm, multicentre randomised controlled trial, economic analysis and process evaluation. SETTING: NHS stroke services. PARTICIPANTS: adults with acute or chronic first-ever stroke (1 week to 5 years post stroke) causing moderate to severe upper limb functional limitation. Randomisation groups: 1. Robot-assisted training using the InMotion robotic gym system for 45 min, three times/week for 12 weeks 2. Enhanced upper limb therapy for 45 min, three times/week for 12 weeks 3. Usual NHS care in accordance with local clinical practice Randomisation: individual participant randomisation stratified by centre, time since stroke, and severity of upper limb impairment. PRIMARY OUTCOME: upper limb function measured by the Action Research Arm Test (ARAT) at 3 months post randomisation. SECONDARY OUTCOMES: upper limb impairment (Fugl-Meyer Test), activities of daily living (Barthel ADL Index), quality of life (Stroke Impact Scale, EQ-5D-5L), resource use, cost per quality-adjusted life year and adverse events, at 3 and 6 months. Blinding: outcomes are undertaken by blinded assessors. Economic analysis: micro-costing and economic evaluation of interventions compared to usual NHS care. A within-trial analysis, with an economic model will be used to extrapolate longer-term costs and outcomes. Process evaluation: semi-structured interviews with participants and professionals to seek their views and experiences of the rehabilitation that they have received or provided, and factors affecting the implementation of the trial. SAMPLE SIZE: allowing for 10% attrition, 720 participants provide 80% power to detect a 15% difference in successful outcome between each of the treatment pairs. Successful outcome definition: baseline ARAT 0-7 must improve by 3 or more points; baseline ARAT 8-13 improve by 4 or more points; baseline ARAT 14-19 improve by 5 or more points; baseline ARAT 20-39 improve by 6 or more points. DISCUSSION: The results from this trial will determine whether robot-assisted training improves upper limb function post stroke. TRIAL REGISTRATION: ISRCTN, identifier: ISRCTN69371850 . Registered 4 October 2013