ADAR-mediated RNA editing suppresses sleep by acting as a brake on glutamatergic synaptic plasticity.

It has been postulated that synaptic potentiation during waking is offset by a homoeostatic reduction in net synaptic strength during sleep. However, molecular mechanisms to support such a process are lacking. Here we demonstrate that deficiencies in the RNA-editing gene Adar increase sleep due to synaptic dysfunction in glutamatergic neurons in Drosophila. Specifically, the vesicular glutamate transporter is upregulated, leading to over-activation of NMDA receptors, and the reserve pool of glutamatergic synaptic vesicles is selectively expanded in Adar mutants. Collectively these changes lead to sustained neurotransmitter release under conditions that would otherwise result in synaptic depression. We propose that a shift in the balance from synaptic depression towards synaptic potentiation in sleep-promoting neurons underlies the increased sleep pressure of Adar-deficient animals. Our findings provide a plausible molecular mechanism linking sleep and synaptic plasticity

Co-creating and directing Innovation Ecosystems? NASA's changing approach to public-private partnerships in low-earth orbit

U.S. public activities in space directed via NASA are undergoing change. While NASA has historically been able to drive market creation, through its procurement policy (which is much weaker in Europe), the past decade has seen a visible shift in US space policy, away from NASA-directed developments in low-Earth orbit (LEO) towards an ecosystem with a mix of private, not-for-profit, and public actors in LEO. This has fundamentally changed NASA's role from an orchestrating/directing role, to a more ‘facilitating’ one driven by commercialization needs. This shift in mission and approach has ramifications for the LEO ecosystem as well as NASA's innovation policy, which has previously centred on clearly defined “mission-oriented” objectives, such as putting a man on the moon or creating the shuttle fleet. Such objectives required ‘active’ innovation policy whereby NASA both funded and ‘directed’ the innovation, within its walls and with its partners. The emerging multi-actor ecosystem approach has involved a more open-ended objective that does not have a unified nor clearly defined end-game. In this situation, NASA's ability to shape activities in a direction in line with its mission will depend on its relationships with other members in the system. The rise of new actors in the space eco-system, and new relationships between them, presents interesting challenges for innovation policy informed by an Innovation System approach. In this paper, we critique the market failure approach of public intervention in markets and describe further work to be done in the innovation systems literature - more focus on the interactions between agents (and the type of agents) as complimentary to the dominant focus on funding programmes in innovation systems. In this paper, we present the evolving processes of NASA's engagement in building a low-earth orbit economy to draw out case specific insights into a public agency shifting its mission to incorporate approaches to facilitate the market creation policy. The paper focuses on the way that NASA structures its new innovation policy, away from a classical supply side oriented R&D investment through NASA itself, towards a policy of orchestration and combination of instruments rather. We close the paper with a reflection on the ramifications of NASA's approach to building a sustainable low-Earth orbit economic ecosystem

Wetland fish communities above stream regulators with and without fish passage in Lao PDR

We have implemented a multiple lines of evidence approach to assessing the efficacy of fishways in the Houay (small stream) Peung and Houay Souy, Lao PDR. The methods include socio-economic surveys of households, direct observation of fisherman catch, trapping within the fishways, and surveys of fish assemblages in each fishway wetland, along with comparison wetlands that do not have a fishway installed. The in-wetland surveys are designed to be a long-term program and in this presentation I report on the design, monitoring and preliminary results. Whilst there are several differences in the types of fish present in each of the wetlands, there was no statistically significant difference in the CPUE, species richness or the composition of fish assemblages between fishway wetlands and comparison wetlands, regardless of season, during the first two years of our study. This is consistent with previous studies, that found only one or two species are likely to respond in the first few years and it may take 4 or more seasons of operations for major compositional changes in assemblages to be recognised. Our results are consistent with expectations from pre-fishway operations and the monitoring program is well placed to detect changes as the fishways enter full operational mode. We also discuss the implications of high fishing pressure in these wetlands and how this may affect the rate of change and detection of those changes

Identifying children with Cystic Fibrosis in population-scale routinely collected data in Wales

IntroductionThe challenges in identifying a cohort of people with a rare condition can be addressed by routinely collected, population-scale electronic health record (EHR) data, which provide large volumes of data at a national level. This paper describes the challenges of accurately identifying a cohort of children with Cystic Fibrosis (CF) using EHR and their validation against the UK CF Registry.ObjectivesTo establish a proof of principle and provide insight into the merits of linked data in CF research; to identify the benefits of access to multiple data sources, in particular the UK CF Registry data, and to demonstrate the opportunity it represents as a resource for future CF research.MethodsThree EHR data sources were used to identify children with CF born in Wales between 1st January 1998 and 31st August 2015 within the Secure Anonymised Information Linkage (SAIL) Databank. The UK CF Registry was later acquired by SAIL and linked to the EHR cohort to validate the cases and explore the reasons for misclassifications.ResultsWe identified 352 children with CF in the three EHR data sources. This was greater than expected based on historical incidence rates in Wales. Subsequent validation using the UK CF Registry found that 257 (73%) of these were true cases. Approximately 98.7% (156/158) of individuals identified as CF cases in all three EHR data sources were confirmed as true cases; but this was only the case for 19.8% (20/101) of all those identified in just a single data source.ConclusionIdentifying health conditions in EHR data can be challenging, so data quality assurance and validation is important or the merit of the research is undermined. This retrospective review identifies some of the challenges in identifying CF cases and demonstrates the benefits of linking cases across multiple data sources to improve quality

Analysis of rare copy number variation in absence epilepsies.

OBJECTIVE: To identify shared genes and pathways between common absence epilepsy (AE) subtypes (childhood absence epilepsy [CAE], juvenile absence epilepsy [JAE], and unclassified absence epilepsy [UAE]) that may indicate common mechanisms for absence seizure generation and potentially a diagnostic continuum. METHODS: We used high-density single-nucleotide polymorphism arrays to analyze genome-wide rare copy number variation (CNV) in a cohort of 144 children with AEs (95 CAE, 26 UAE, and 23 JAE). RESULTS: We identified CNVs that are known risk factors for AE in 4 patients, including 3x 15q11.2 deletion. We also expanded the phenotype at 4 regions more commonly identified in other neurodevelopmental disorders: 1p36.33 duplication, 1q21.1 deletion, 22q11.2 duplication, and Xp22.31 deletion and duplication. Fifteen patients (10.5%) were found to carry rare CNVs that disrupt genes associated with neuronal development and function (8 CAE, 2 JAE, and 5 UAE). Four categories of protein are each disrupted by several CNVs: (1) synaptic vesicle membrane or vesicle endocytosis, (2) synaptic cell adhesion, (3) synapse organization and motility via actin, and (4) gap junctions. CNVs within these categories are shared across the AE subtypes. CONCLUSIONS: Our results have reinforced the complex and heterogeneous nature of the AEs and their potential for shared genetic mechanisms and have highlighted several pathways that may be important in epileptogenesis of absence seizures

The air raids that never were and the war that nobody won: government propaganda in conflict reporting and how journalists should respond to it

During the bombing campaign against Libya in the spring of 2011, the fog of war enveloped not only the shifting frontlines of the battles between forces loyal to the then Libyan leader, Muammar Gaddafi, but also the more comfortable surroundings of British government ministries. A news story of an aborted air raid reflected the huge importance which governments increasingly place upon getting their message across in the international media in times of conflict. Looking at that example from the conflict in Libya, and studying in detail others from Russia’s 2008 war with Georgia, this article argues that journalists must correspondingly be increasingly aware of attempts by governments, and their hired public relations hands, to influence reporting

Preventive medical care in remote Aboriginal communities in the Northern Territory: a follow-up study of the impact of clinical guidelines, computerised recall and reminder systems, and audit and feedback

Background Interventions to improve delivery of preventive medical services have been shown to be effective in North America and the UK. However, there are few studies of the extent to which the impact of such interventions has been sustained, or of the impact of such interventions in disadvantaged populations or remote settings. This paper describes the trends in delivery of preventive medical services following a multifaceted intervention in remote community health centres in the Northern Territory of Australia. Methods The intervention comprised the development and dissemination of best practice guidelines supported by an electronic client register, recall and reminder systems and associated staff training, and audit and feedback. Clinical records in seven community health centres were audited at regular intervals against best practice guidelines over a period of three years, with feedback of audit findings to health centre staff and management. Results Levels of service delivery varied between services and between communities. There was an initial improvement in service levels for most services following the intervention, but improvements were in general not fully sustained over the three year period. Conclusions Improvements in service delivery are consistent with the international experience, although baseline and follow-up levels are in many cases higher than reported for comparable studies in North America and the UK. Sustainability of improvements may be achieved by institutionalisation of relevant work practices and enhanced health centre capacity

Simulating radiation damage cascades in graphite

Molecular dynamics simulation is used to study radiation damage cascades in graphite. High statistical precision is obtained by sampling a wide energy range (100–2500 eV) and a large number of initial directions of the primary knock-on atom. Chemical bonding is described using the Environment Dependent Interaction Potential for carbon. Graphite is found to exhibit a radiation response distinct from metals and oxides primarily due to the absence of a thermal spike which results in point defects and disconnected regions of damage. Other unique attributes include exceedingly short cascade lifetimes and fractal-like atomic trajectories. Unusually for a solid, the binary collision approximation is useful across a wide energy range, and as a consequence residual damage is consistent with the Kinchin–Pease model. The simulations are in agreement with known experimental data and help to clarify substantial uncertainty in the literature regarding the extent of the cascade and the associated damage

Exoplanet Atmosphere Measurements from Transmission Spectroscopy and other Planet-Star Combined Light Observations

It is possible to learn a great deal about exoplanet atmospheres even when we cannot spatially resolve the planets from their host stars. In this chapter, we overview the basic techniques used to characterize transiting exoplanets - transmission spectroscopy, emission and reflection spectroscopy, and full-orbit phase curve observations. We discuss practical considerations, including current and future observing facilities and best practices for measuring precise spectra. We also highlight major observational results on the chemistry, climate, and cloud properties of exoplanets.Comment: Accepted review chapter; Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag). 22 pages, 6 figure