Apparently synonymous substitutions in FGFR2affect splicing and result in mild Crouzon syndrome

BACKGROUND: Mutations of fibroblast growth factor receptor 2 (FGFR2) account for a higher proportion of genetic cases of craniosynostosis than any other gene, and are associated with a wide spectrum of severity of clinical problems. Many of these mutations are highly recurrent and their associated features well documented. Crouzon syndrome is typically caused by heterozygous missense mutations in the third immunoglobulin domain of FGFR2. CASE PRESENTATION: Here we describe two families, each segregating a different, previously unreported FGFR2 mutation of the same nucleotide, c.1083A>G and c.1083A>T, both of which encode an apparently synonymous change at the Pro361 codon. We provide experimental evidence that these mutations affect normal FGFR2 splicing and document the clinical consequences, which include a mild Crouzon syndrome phenotype and reduced penetrance of craniosynostosis. CONCLUSIONS: These observations add to a growing list of FGFR2 mutations that affect splicing and provide important clinical information for genetic counselling of families affected by these specific mutations

Energy and the military: Convergence of security, economic, and environmental decision-making

Energy considerations are core to the missions of armed forces worldwide. The interaction between military energy issues and non-military energy issues is not often explicitly treated in the literature or media, although issues around clean energy have increased awareness of this interaction. The military has also long taken a leadership role on research and development (R&D) and procurement of specific energy technologies. More recently, R&D leadership has moved to the energy efficiency of home-country installations, and the development of renewable energy projects for areas as diverse as mini-grids for installations, to alternative fuels for major weapons systems. In this paper we explore the evolving relationship between energy issues and defense planning, and show how these developments have implications for military tactics and strategy as well as for civilian energy policy

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

Presidents and policy-making: has Brazil's CCT-led anti-poverty agenda gone far enough?

In order to identify the causal mechanisms (rational learning, adaptation, and innovation) driving changes in the area of anti-poverty policy in Brazil, this article traces the micro-level decision-making processes across three presidents. It begins by laying out the politics of conditional cash transfers (CCTs) in Brazil and presidential usage of this targeted social policy instrument since the 1990s. In contrast to previous presidents, President Dilma Rousseff’s decisions did not enable her rationally intended policy agenda. Why? The President him or herself is privileged as the central actor whose decision-making processes impact policy development and its subsequent performance. I will argue that prior to the most recent changes under Dilma, was the demise of CCTs being ‘good enough’ from a policy perspective. The major challenge for any president in Brazil remains low levels of political and societal consensus over the kind of social reforms required to end the intergenerational transmission of poverty in Brazil; a policy dilemma confounded by the absence of a single unifying institutional actor and the extent of power diffusion in Brazilian federalis