The introduction of new interventional procedures in the British National Health Service : A qualitative study

Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.Peer reviewedPostprin

Disk Heating, Galactoseismology, and the Formation of Stellar Halos

Deep photometric surveys of the Milky Way have revealed diffuse structures encircling our Galaxy far beyond the "classical" limits of the stellar disk. This paper reviews results from our own and other observational programs, which together suggest that, despite their extreme positions, the stars in these structures were formed in our Galactic disk. Mounting evidence from recent observations and simulations implies kinematic connections between several of these distinct structures. This suggests the existence of collective disk oscillations that can plausibly be traced all the way to asymmetries seen in the stellar velocity distribution around the Sun. There are multiple interesting implications of these findings: they promise new perspectives on the process of disk heating, they provide direct evidence for a stellar halo formation mechanism in addition to the accretion and disruption of satellite galaxies, and, they motivate searches of current and near-future surveys to trace these oscillations across the Galaxy. Such maps could be used as dynamical diagnostics in the emerging field of "Galactoseismology", which promises to model the history of interactions between the Milky Way and its entourage of satellites, as well examine the density of our dark matter halo. As sensitivity to very low surface brightness features around external galaxies increases, many more examples of such disk oscillations will likely be identified. Statistical samples of such features not only encode detailed information about interaction rates and mergers, but also about long sought-after dark matter halo densities and shapes. Models for the Milky Way's own Galactoseismic history will therefore serve as a critical foundation for studying the weak dynamical interactions of galaxies across the universe.Comment: 20 pages, 5 figures, accepted in for publication in a special edition of the journal "Galaxies", reporting the proceedings of the conference "On the Origin (and Evolution) of Baryonic Galaxy Halos", Puerto Ayora, Ecuador, March 13-17 2017, Eds. Duncan A. Forbes and Ericson D. Lope

Community transcriptomics reveals universal patterns of protein sequence conservation in natural microbial communities

Background Combined metagenomic and metatranscriptomic datasets make it possible to study the molecular evolution of diverse microbial species recovered from their native habitats. The link between gene expression level and sequence conservation was examined using shotgun pyrosequencing of microbial community DNA and RNA from diverse marine environments, and from forest soil. Results Across all samples, expressed genes with transcripts in the RNA sample were significantly more conserved than non-expressed gene sets relative to best matches in reference databases. This discrepancy, observed for many diverse individual genomes and across entire communities, coincided with a shift in amino acid usage between these gene fractions. Expressed genes trended toward GC-enriched amino acids, consistent with a hypothesis of higher levels of functional constraint in this gene pool. Highly expressed genes were significantly more likely to fall within an orthologous gene set shared between closely related taxa (core genes). However, non-core genes, when expressed above the level of detection, were, on average, significantly more highly expressed than core genes based on transcript abundance normalized to gene abundance. Finally, expressed genes showed broad similarities in function across samples, being relatively enriched in genes of energy metabolism and underrepresented by genes of cell growth. Conclusions These patterns support the hypothesis, predicated on studies of model organisms, that gene expression level is a primary correlate of evolutionary rate across diverse microbial taxa from natural environments. Despite their complexity, meta-omic datasets can reveal broad evolutionary patterns across taxonomically, functionally, and environmentally diverse communities.Gordon and Betty Moore FoundationAgouron InstituteNational Science Foundation (U.S.)Center for Microbial Oceanography: Research and Educatio

Report of the three-day workshop on 'Regeneration of the Banas-Bisalpur Socio-ecological Complex'

Executive summaryThe ‘Regeneration of the Banas-Bisalpur Socio-ecological Complex’ workshop (JK Lakshmipat University, Jaipur, December 2017) brought together approximately 70 participants from government, NGOs, academia, village governance institutions and Corporate Social Responsibility (CSR) programmes sharing an interest in reversal of the currently degrading cycle of linked ecological and socioeconomic degradation across the Banas River catchment in Rajasthan. The workshop was run in association with the University of the West of England (UWE Bristol, UK), JK Lakshmipat University (Jaipur, India), and WaterHarvest – India Liaison Office (Udaipur, India), and was kindly sponsored by Wetlands International – South Asia Office (Delhi, India).Like many catchments globally, the Banas has not been treated in modern times as a living resource. Rather, it has been subject to high levels of abstraction without proportional rebalancing resource renewal, putting the socio-ecological system into degrading cycle. Yet, for four-and-a-half thousand years of pre-industrial history, the people of Rajasthan had subsisted and thrived on scarce water by innovation and operation of a diversity of ‘water wise’ recharge, storage and efficient use solutions attuned to local geography and culture. A key challenge for reversal of the currently rapidly degrading cycle in the Banas catchment, with its associated vulnerabilities for all inherently interconnected urban and rural people co-dependent on its water, is to recognise the central role played by the primary resource of ecosystem processes.Workshop participants welcomed the opportunity to work together to explore problems, emerging needs and potential solutions, and to do so as part of an ongoing strategy of ‘action learning’ towards a vision of a regenerative socio-ecological system. Future progress entails working together to co-develop solutions that work with natural processes, hybridising traditional knowledge and modern techniques to achieve a regenerative socio-ecological cycle better connected across the catchment in a modern world of significant population growth, urbanisation and climate change. Cross-catchment connections include closer integration and equitable balance between needs and appropriate solutions that work for all people, with the current fracture of perspectives between urban and rural regions highlighted as a particular priority for action. Economic and regulatory reforms attuned to supporting environmental processes are essential, backed up by research in environmental and social systems, engineering, economics and governance mechanisms. Shared awareness and responsibility by all people across the catchment is necessary to achieve a more integrated approach to catchment sustainability, including reducing current fragmentation of institutions and knowledge. NGOs, village governance institutions and faith leaders have significant roles to play in integrating effort and knowledge, along with government, CSR and academic programmes.All technologies, both ecosystem-based and ‘hard’ engineering techniques, have roles to play, but the ramifications of their deployment need to be understood. An agreed foundational goal within the Banas vision is sustainable hybridisation of water management technologies –natural infrastructure, traditional management, ‘green’ technologies and ‘hard’ engineering – in ways that are beneficial to local people and catchment processes. This is vital to reverse current and cumulative cumulate pressures arising from proliferation of unlicenced tube wells and large dam-and-transfer schemes that are not today balanced with recharge, constituting primary drivers of catchment decline. Water efficiency in urban area, responsible for a high density of demand, is substantially underinvested today. Novel urban self-sufficiency, benefit sharing and investment mechanisms to regenerate the resource are required, overcoming former narrow exploitation-based approaches founded on limited knowledge and power asymmetries. Novel ideas include limiting water diversions from the Bisalpur to the city of Jaipur, quantitatively or on a time-limited basis, as a means to force greater awareness and self-reliance on local urban sources (such as investment in infiltration pits and local storage) and ‘green infrastructure’ solutions (rooftop water harvesting, greywater reuse, etc.) to redress power asymmetries and assumptions, and to promote urban self-sufficiency.Some knowledge gaps and incorrect assumptions need to be addressed. This includes in particular divergent opinions about the impact of small anicuts in upper sub-catchments, seen by some a stopping water reaching the Bisapur Dam but by others as sustaining local livelihoods whilst also regenerating groundwater systems that store and buffer flows downstream. There is also a need to better understand underground and surface flows of water in the catchment as a robust basis for more sustainable management, and to improve the protection of this vital natural capital to combat poverty and better support human needs.Novel livelihood practices could be innovated to make better beneficial use of water within the catchment, rather than depending on abstraction from the ecosystem to drive short-term consumptive economic uses. The economics of water include thinking in a cyclic way consistent with the water cycle, for example directing investment in upstream practices that recharge the catchment system rather than simply using it to increase the technical efficiency of extractive technologies that the current declines in water quantity and quality will render unsustainable. Reformed economic instruments are part of a wider transition to cyclic thinking and behaviour, also addressing equity issues, creating a regulatory environment across the catchment that works in synergy with its natural supportive and regenerative processes.Reaching for a regenerative vision necessarily includes innovating effective, nested governance systems. A ‘top down’ catchment-scale vision and enabling policy environment is necessary to inform and facilitate progress towards the catchment-wide vision, also helping enforce practices such as driving roof water harvesting, water efficiency and reuse, and other necessary efficiency measures in urban areas. However, practical delivery requires a high level of delegation to identify and deploy solutions closely tuned to specific geographical and cultural situations, that are best innovated and governed on a highly localised basis. Enabling, nested and co-creative governance arrangement are required. This includes far closer integration of the disparate CSR, NGO, local, faith leader and government programmes (MGNREGA, Smart Cities, Rajasthan’s MJSA programme, and many more departmental initiatives and associated budgets that are currently narrowly deployed). This can be implemented with far greater synergy and cross-departmental co-benefits leading towards the ultimate vision of a regenerative socio-ecological system.'Business as usual’ – today’s overemphasis on technically efficient extraction, overlooking ecosystem processes underpinning resource recharge and availability – is not a sustainable option, and can only perpetuate ecological depletion and associated human vulnerabilities. There is now no viable, equitable or sustainable alternative than acting upon what we now know about the systemic nature of catchments, and refocusing energies, investment and innovation on an ecosystem- and community-based regeneration programme for the Banas socio-ecological system. There is a pressing need to change paradigm from narrowly short-term exploitation, leading to the depletion of water and associated ecological and human wellbeing, towards more informed and strategic stewardship with efficient uses balanced with resource protection and regeneration.Workshop participants saw substantial value in bringing people together from a diversity of societal sectors associated with the catchment, welcoming future opportunities to share perspectives and make strides towards co-created sustainable solutions. Ecosystems and their processes were acknowledged as the fundamental resource underpinning continuing human security and opportunity, and need to be valued on that basis in all management and use decisions within a bold vision of a regenerative socio-ecological Banas system. Though the challenges of attaining it are daunting, confronting many assumed norms and vested interests, this vision can be focal for progressive innovation, evolution and integration of initiatives, to get as close as possible to a baseline of natural catchment functioning and sustainable human interactions with it.Above all, the tight interlinkage between all people co-dependent on the catchment system needs to be recognised within a collaborative approach to balance water use with recharge, regenerating the entire socio-ecological system. This is “a journey, not a destination” that all participants are happy to progress

Internet Predictions

More than a dozen leading experts give their opinions on where the Internet is headed and where it will be in the next decade in terms of technology, policy, and applications. They cover topics ranging from the Internet of Things to climate change to the digital storage of the future. A summary of the articles is available in the Web extras section

Exploring Halo Substructure with Giant Stars. XV. Discovery of a Connection between the Monoceros Ring and the Triangulum-Andromeda Overdensity?

Thanks to modern sky surveys, over twenty stellar streams and overdensity structures have been discovered in the halo of the Milky Way. In this paper, we present an analysis of spectroscopic observations of individual stars from one such structure, "A13", first identified as an overdensity using the M giant catalog from the Two Micron All-Sky Survey. Our spectroscopic observations show that stars identified with A13 have a velocity dispersion of $\lesssim$ 40 $\mathrm{km~s^{-1}}$, implying that it is a genuine coherent structure rather than a chance super-position of random halo stars. From its position on the sky, distance ($\sim$15~kpc heliocentric), and kinematical properties, A13 is likely to be an extension of another low Galactic latitude substructure -- the Galactic Anticenter Stellar Structure (also known as the Monoceros Ring) -- towards smaller Galactic longitude and farther distance. Furthermore, the kinematics of A13 also connect it with another structure in the southern Galactic hemisphere -- the Triangulum-Andromeda overdensity. We discuss these three connected structures within the context of a previously proposed scenario that one or all of these features originate from the disk of the Milky Way.Comment: 12 pages, 9 figures. Accepted for publication in Ap

Effect of information format on intentions and beliefs regarding diagnostic imaging for non-specific low back pain: A randomised controlled trial in members of the public

Objective To evaluate the effects of information format on intentions to request diagnostic imaging for non-specific low back pain in members of the public. Methods We performed a three arm, 1:1:1, superiority randomised trial on members of the public. Participants were randomised to one of the three groups: a Standard Care Leaflet group (standard information on low back pain), a Neutral Leaflet group (balanced information on the benefits and harms of imaging) and a Nudge Leaflet group (with behavioural cues to emphasise the harms of unnecessary imaging). Our primary outcome was intention to request imaging for low back pain. Results 418 participants were randomised. After reading the leaflet, intention to request imaging (measured on an 11-point scale (0 = definitely would not request to 10 = definitely would request) was lower in the Nudge Leaflet group (mean = 4.6, SD = 3.4) compared with the Standard Care Leaflet group (mean = 5.3, SD = 3.3) and the Neutral Leaflet group (mean = 5.3, SD = 3.0) (adjusted mean difference between Nudge and Neutral, −1.0 points, 95%CI −1.6 to −0.4). Conclusion Framing information to emphasise potential harms from overdiagnosis reduced intention to request diagnostic imaging for low back pain. Practice implications Nudge leaflets could help clinicians manage patient pressure for unnecessary tests.Dr Mary O'Keeffe is supported by funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 75049

Evolution of rhodopsin ion pumps in haloarchaea

<p>Abstract</p> <p>Background</p> <p>The type 1 (microbial) rhodopsins are a diverse group of photochemically reactive proteins that display a broad yet patchy distribution among the three domains of life. Recent work indicates that this pattern is likely the result of lateral gene transfer (LGT) of rhodopsin genes between major lineages, and even across domain boundaries. Within the lineage in which the microbial rhodopsins were initially discovered, the haloarchaea, a similar patchy distribution is observed. In this initial study, we assess the roles of LGT and gene loss in the evolution of haloarchaeal rhodopsin ion pump genes, using phylogenetics and comparative genomics approaches.</p> <p>Results</p> <p>Mapping presence/absence of rhodopsins onto the phylogeny of the RNA polymerase B' subunit (RpoB') of the haloarchaea supports previous notions that rhodopsins are patchily distributed. The phylogeny for the bacteriorhodopsin (BR) protein revealed two discrepancies in comparison to the RpoB' marker, while the halorhodopsin (HR) tree showed incongruence to both markers. Comparative analyses of bacteriorhodopsin-linked regions of five haloarchaeal genomes supported relationships observed in the BR tree, and also identified two open reading frames (ORFs) that were more frequently linked to the bacteriorhodopsin gene than those genes previously shown to be important to the function and expression of BR.</p> <p>Conclusion</p> <p>The evidence presented here reveals a complex evolutionary history for the haloarchaeal rhodopsins, with both LGT and gene loss contributing to the patchy distribution of rhodopsins within this group. Similarities between the BR and RpoB' phylogenies provide supportive evidence for the presence of bacteriorhodopsin in the last common ancestor of haloarchaea. Furthermore, two loci that we have designated bacterio-opsin associated chaperone (<it>bac</it>) and bacterio-opsin associated protein (<it>bap</it>) are inferred to have important roles in BR biogenesis based on frequent linkage and co-transfer with bacteriorhodopsin genes.</p

Unexpected structures formed by the kinase RET C634R mutant extracellular domain suggest potential oncogenic mechanisms in MEN2A

The RET receptor tyrosine kinase plays a pivotal role in cell survival, proliferation, and differentiation, and its abnormal activation leads to cancers through receptor fusions or point mutations. Mutations that disrupt the disulfide network in the extracellular domain (ECD) of RET drive multiple endocrine neoplasia type 2A (MEN2A), a hereditary syndrome associated with the development of thyroid cancers. However, structural details of how specific mutations affect RET are unclear. Here, we present the first structural insights into the ECD of the RET(C634R) mutant, the most common mutation in MEN2A. Using electron microscopy, we demonstrate that the C634R mutation causes ligand-independent dimerization of the RET ECD, revealing an unusual tail-to-tail conformation that is distinct from the ligand-induced signaling dimer of WT RET. Additionally, we show that the RETC634R ECD dimer can form complexes with at least two of the canonical RET ligands and that these complexes form very different structures than WT RET ECD upon ligand binding. In conclusion, this structural analysis of cysteine-mutant RET ECD suggests a potential key mechanism of cancer induction in MEN2A, both in the absence and presence of its native ligands, and may offer new targets for therapeutic intervention.Peer reviewe