An integrated Rotorcraft Avionics/Controls Architecture to support advanced controls and low-altitude guidance flight research

Salient design features of a new NASA/Army research rotorcraft--the Rotorcraft-Aircrew Systems Concepts Airborne Laboratory (RASCAL) are described. Using a UH-60A Black Hawk helicopter as a baseline vehicle, the RASCAL will be a flying laboratory capable of supporting the research requirements of major NASA and Army guidance, control, and display research programs. The paper describes the research facility requirements of these programs together with other critical constraints on the design of the research system. Research program schedules demand a phased development approach, wherein specific research capability milestones are met and flight research projects are flown throughout the complete development cycle of the RASCAL. This development approach is summarized, and selected features of the research system are described. The research system includes a real-time obstacle detection and avoidance system which will generate low-altitude guidance commands to the pilot on a wide field-of-view, color helmet-mounted display and a full-authority, programmable, fault-tolerant/fail-safe, fly-by-wire flight control system

Preliminary design features of the RASCAL: A NASA /Army rotorcraft in-flight simulator

Salient design features of a new NASA/Army research rotorcraft - the Rotorcraft-Aircrew Systems Concepts Airborne Laboratory (RASCAL) - are described. Using a UH-60A Black Hawk helicopter as a baseline vehicle, the RASCAL will be a flying laboratory capable of supporting the research requirements of major NASA and Army guidance, control, and display research programs. The paper describes the research facility requirements of these programs together with other critical constraints on the design of the research system, including safety-of-flight. Research program schedules demand a phased development approach, wherein specific research capability milestones are met and flight research projects are flown throughout the complete development cycle of the RASCAL. This development approach is summarized, and selected features of the research system are described. The research system includes a full-authority, programmable, fault-tolerant/fail-safe, fly-by-wire flight control system and a real-time obstacle detection and avoidance system which will generate low-altitude guidance commands to the pilot on a wide field-of-view, color helmet-mounted display

First-in-Human Clinical Trial of Oral ONC201 in Patients with Refractory Solid Tumors

Purpose: ONC201 is a small-molecule selective antagonist of the G protein–coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D). Experimental Design: This open-label study treated 10 patients during dose escalation with histologically confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design. An additional 18 patients were treated at the RP2D in an expansion phase to collect additional safety, pharmacokinetic, and pharmacodynamic information. Results: No grade \u3e 1 drug-related adverse events occurred, and the RP2D was defined as 625 mg. Pharmacokinetic analysis revealed a Cmax of 1.5 to 7.5 μg/mL (∼3.9–19.4 μmol/L), mean half-life of 11.3 hours, and mean AUC of 37.7 h·μg/L. Pharmacodynamic assays demonstrated induction of caspase-cleaved keratin 18 and prolactin as serum biomarkers of apoptosis and DRD2 antagonism, respectively. No objective responses by RECIST were achieved; however, radiographic regression of several individual metastatic lesions was observed along with prolonged stable disease (\u3e 9 cycles) in prostate and endometrial cancer patients. Conclusions: ONC201 is a selective DRD2 antagonist that is well tolerated, achieves micromolar plasma concentrations, and is biologically active in advanced cancer patients when orally administered at 625 mg every 3 weeks

Planned Marketing Adaptation and Multinationals' Choices Between Acquisitions and Greenfields

International marketing studies have extensively examined the antecedents of firms' marketing standardization/ adaptation decisions. However, it is unclear whether such decisions, once planned, codetermine the choice between buying and building foreign subsidiaries. Analyzing a sample of 150 foreign entries by Dutch firms, the authors find that the level of marketing adaptation planned for a wholly owned subsidiary is positively related to the likelihood that the subsidiary will be established through an acquisition rather than through a greenfield investment. Moreover, the authors find substantial evidence that this positive relationship is stronger for firms that (1) are establishing relatively larger subsidiaries, (2) have less experience with the industry entered, or (3) are entering less developed countries. The findings show that firms pursuing higher levels of marketing adaptation assign more value to the marketing adaptation advantages of acquisitions over greenfields, especially if the risks associated with implementing the planned adaptation level are high. In addition, firms typically strive for a fit between their international marketing strategy and their mode of foreign establishment. (authors' abstract

Work and Welfare in the American States: Analyzing the Effects of the JOBS Program

This research seeks to determine whether the Job Opportunities and Basic Skills GOBS) program (established under the 1988 Family Support Act) was successful in reducing the number of welfare recipients among U.S. states for the period 1984 to 1996. Within the context of two theoretical perspectives-developmental and rational choice-we assess the impact of JOBS on AFDC participation rates using a pooled time-series design. At best, JOBS had a minimal effect. We estimate that states with higher proportions of their AFDC populations enrolled in JOBS programs had only slightly lower rates of participation in AFDC. Other forces were far more influential in reducing welfare participation. In particular, states with higher per capita income, lower female unemployment rates, lower poverty rates, and higher wages for low-paying jobs had the lowest welfare recipiency The AFDC participation rates of neighboring states had a significant effect, as well. The analysis showed that more generous AFDC benefits exerted strong upward pressure on a state's welfare rolls.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Maternal but not fetoplacental health can be improved by metformin in a murine diet-induced model of maternal obesity and glucose intolerance.

Maternal obesity is a global problem that increases the risk of short- and long-term adverse outcomes for mother and child, many of which are linked to gestational diabetes mellitus. Effective treatments are essential to prevent the transmission of poor metabolic health from mother to child. Metformin is an effective glucose lowering drug commonly used to treat gestational diabetes mellitus; however, its wider effects on maternal and fetal health are poorly explored. In this study we used a mouse (C57Bl6/J) model of diet-induced (high sugar/high fat) maternal obesity to explore the impact of metformin on maternal and feto-placental health. Metformin (300 mg kg-1  day-1 ) was given to obese females via the diet and was shown to achieve clinically relevant concentrations in maternal serum (1669 ± 568 nM in late pregnancy). Obese dams developed glucose intolerance during pregnancy and had reduced uterine artery compliance. Metformin treatment of obese dams improved maternal glucose tolerance, reduced maternal fat mass and restored uterine artery function. Placental efficiency was reduced in obese dams, with increased calcification and reduced labyrinthine area. Consequently, fetuses from obese dams weighed less (P < 0.001) at the end of gestation. Despite normalisation of maternal parameters, metformin did not correct placental structure or fetal growth restriction. Metformin levels were substantial in the placenta and fetal circulation (109.7 ± 125.4 nmol g-1 in the placenta and 2063 ± 2327 nM in fetal plasma). These findings reveal the distinct effects of metformin administration during pregnancy on mother and fetus and highlight the complex balance of risk vs. benefits that are weighed in obstetric medical treatments. KEY POINTS: Maternal obesity and gestational diabetes mellitus have detrimental short- and long-term effects for mother and child. Metformin is commonly used to treat gestational diabetes mellitus in many populations worldwide but the effects on fetus and placenta are unknown. In a mouse model of diet-induced obesity and glucose intolerance in pregnancy we show reduced uterine artery compliance, placental structural changes and reduced fetal growth. Metformin treatment improved maternal metabolic health and uterine artery compliance but did not rescue obesity-induced changes in the fetus or placenta. Metformin crossed the placenta into the fetal circulation and entered fetal tissue. Metformin has beneficial effects on maternal health beyond glycaemic control. However, despite improvements in maternal physiology, metformin did not prevent fetal growth restriction or placental ageing. The high uptake of metformin into the placental and fetal circulation highlights the potential for direct immediate effects of metformin on the fetus with possible long-term consequences postnatally

Healthcare quality improvement and ‘work engagement’; concluding results from a national, longitudinal, cross-sectional study of the ‘Productive Ward-Releasing Time to Care’ programme

Concerns about patient safety and reducing harm have led to a particular focus on initiatives that improve healthcare quality. However Quality Improvement (QI) initiatives have in the past typically faltered because they fail to fully engage healthcare professionals, resulting in apathy and resistance amongst this group of key stakeholders. Productive Ward: Releasing Time to Care (PW) is a ward-based QI programme created to help ward-based teams redesign and streamline the way that they work; leaving more time to care for patients. PW is designed to engage and empower ward-based teams to improve the safety, quality and delivery of care

Can Healthcare Assistant Training (CHAT) improve the relational care of older people? Study protocol for a pilot cluster-randomised controlled trial

Background People aged 75 years and over account for one in four of all hospital admissions. There has been increasing recognition of problems in the care of older people, particularly in hospitals. Evidence suggests that older people judge the care they receive in terms of kindness, empathy, compassion, respectful communication and being seen as a person not just a patient. These are aspects of care to which we refer when we use the term 'relational care'. Healthcare assistants deliver an increasing proportion of direct care to older people, yet their training needs are often overlooked. Methods/design This study will determine the acceptability and feasibility of a cluster randomised controlled trial of 'Older People's Shoes' a two-day training intervention for healthcare assistants caring for older people in hospital. Within this pilot, two-arm, parallel, cluster randomised controlled trial, healthcare assistants within acute hospital wards are randomised to either the two-day training intervention or training as usual. Registered nurses deliver 'Older People's Shoes' over two days, approximately one week apart. It contains three components: experiential learning about ageing, exploration of older people's stories, and customer care. Outcomes will be measured at the level of patient (experience of emotional care and quality of life during their hospital stay), healthcare assistant (empathy and attitudes towards older people), and ward (quality of staff/patient interaction). Semi-structured interviews of a purposive sample of healthcare assistants receiving the intervention, and all trainers delivering the intervention, will be undertaken to gain insights into the experiences of both the intervention and the trial, and its perceived impact on practice. Trial registration The study was registered as an International Standard Randomised Contolled Trial (ISRCTN10385799) on 29 December 2014