113 research outputs found

    Evaluation of the Air Force’s Determination of the Military Value of the W.K. Kellogg Air Guard Station and the Potential Cost Savings Generated by its Closing

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    This is an evaluation of the methodology used by the Air Force in determining the military value of the W.K. Kellogg Air Guard Station and in estimating the potential costs savings generated by its proposed closing

    Wrist-Worn devices to encourage affected upper limb movement in unilateral cerebral palsy: Participatory design workshops

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    Background: Unilateral (Hemiplegic) cerebral palsy (UCP) causes weakness and stiffness affecting one sided of the body, often impacting activities of daily living. Upper limb therapy at effective intensity is not accessible to most. Aim: To determine stakeholder views on design of an approach using wrist-worn devices and a smartphone application to encourage use of the affected upper limb for children with hemiplegia. Method: Four participatory design workshops and one young people's advisory group workshop incorporating views of five young people with hemiplegia, 13 typically developing peers aged 8–18 years, four parents, three occupational therapists, one teacher and two paediatricians. Two special educational needs co-ordinators were consulted separately. Peers were included to explore a study design whereby each child with hemiplegia would have a participating “buddy”. Topics included views on an acceptable wrist-worn device and smartphone application, participant age range, involvement of a buddy, and barriers to using the technology in a school setting. Ethical/welfare considerations included data security, and potential risks around providing smartphones to young children. Results: Children wanted a comfortable, conventional-appearing wristband incorporating a watch face and a secure, well-fitting strap. They were prepared to wear a band on each wrist. They wanted support with explaining the study to schoolteachers. Most schools restricted smartphone use during the school day: the study design accommodated this. Children agreed with a game as reward but had different views on an acceptable game; direct access to feedback data was preferred by some. Parents commented on the lack of access to upper limb therapy for children with UCP; therapists concurred. The proposed participant age range was widened based on feedback. Typically developing children were prepared to be buddies to help a friend with CP. Stakeholders were reassured by data security explanations and plans to provide internet safety information to participants. Conclusion: The participatory design process informed plans for the proof-of-concept stage of the study, hopefully leading to an approach that will be fun, easy to integrate into everyday life, and have the capacity to increase use of the affected arm and hand

    REFINE (reduced frequency ImmuNE checkpoint inhibition in cancers): A multi-arm phase II basket trial testing reduced intensity immunotherapy across different cancers

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    Background Immune checkpoint inhibitors (ICI) have revolutionised treating advanced cancers. ICI are administered intravenously every 2–6 weeks for up to 2 years, until cancer progression/unacceptable toxicity. Physiological efficacy is observed at lower doses than those used as standard of care (SOC). Pharmacodynamic studies indicate sustained target occupancy, despite a pharmacological half-life of 2–3 weeks. Reducing frequency of administration may be possible without compromising outcomes. The REFINE trial aims to limit individual patient exposure to ICI whilst maintaining efficacy, with potential benefits in quality of life and reduced drug treatment/attendance costs. Methods/Design REFINE is a randomised phase II, multi-arm, multi-stage (MAMS) adaptive basket trial investigating extended interval administration of ICIs. Eligible patients are those responding to conventionally dosed ICI at 12 weeks. In stage I, patients (n = 160 per tumour-specific cohort) will be randomly allocated (1:1) to receive maintenance ICI at SOC vs extended dose interval. REFINE is currently recruiting UK patients with locally advanced or metastatic renal cell carcinoma (RCC) who have tolerated and responded to initial nivolumab/ipilimumab, randomised to receive maintenance nivolumab SOC (480 mg 4 weekly) vs extended interval (480 mg 8 weekly). Additional tumour cohorts are planned. Subject to satisfactory outcomes (progression-free survival) stage II will investigate up to 5 different treatment intervals. Secondary outcome measures include overall survival, quality-of-life, treatment-related toxicity, mean incremental pathway costs and quality-adjusted life-years per patient. REFINE is funded by the Jon Moulton Charity Trust and Medical Research Council, sponsored by University College London (UCL), and coordinated by the MRC CTU at UCL

    Strombolian eruptions and dynamics of magma degassing at Yasur Volcano (Vanuatu)

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    Open vent basaltic volcanoes account for a substantial portion of the global atmospheric outgassing flux, largely through passive degassing and mild explosive activity. We present volcanic gas flux and composition data from Yasur Volcano, Vanuatu collected in July 2018. The average volcanic plume chemistry is characterised by a mean molar CO2/SO2 ratio of 2.14, H2O/SO2 of 148 and SO2/HCl of 1.02. The measured mean SO2 flux in the period of 6th to 9th July is 4.9 kg s−1. Therefore, the mean fluxes of the other species are 7.5 kg∙s−1 CO2, 208 kg∙s−1 H2O and 4.8 kg∙s−1 HCl. The degassing regime at Yasur volcano ranges from ‘passive’ to ‘active’ styles, with the latter including Strombolian activity and spattering. Gases emitted during active degassing are enriched in SO2 over HCl and CO2 over SO2 relative to passive degassing, with CO2/SO2 ratios of 2.85 ± 0.17, SO2/HCl of 1.6 ± 0.22, and H2O/SO2 of 315 ± 78.8. Gases emitted during passive degassing have CO2/SO2 ratios of 1.96 ± 0.12, SO2/HCl of 0.50 ± 0.07 and H2O/SO2 of 174 ± 43.5. We use a model of volatile degassing derived from melt inclusion studies (Metrich et al., 2011), combined with our observations of chemical variations in the outgassing bubbles to propose a mechanism for magma degassing in the conduit at Yasur. We envisage a shallow conduit filled with crystal-rich magma, forming a viscous and mobile plug that develops an effective yield strength from the surface to a depth of at least 2000 m, in which bubbles are trapped, grow, ascend towards the surface and burst in a typical Strombolian eruption. Deeper bubbles released during active degassing are enriched in CO2 and SO2 compared to bubbles released during ‘passive degassing’, which are sourced from close to the surface, and are, consequently, HCl-rich
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