What is the impact of psychiatric decision units on mental health crisis care pathways? Protocol for an interrupted time series analysis with a synthetic control study

Background The UK mental health system is stretched to breaking point. Individuals presenting with mental health problems wait longer at the ED than those presenting with physical concerns and finding a bed when needed is difficult – 91% of psychiatric wards are operating at above the recommended occupancy rate. To address the pressure, a new type of facility – psychiatric decision units (also known as mental health decision units) – have been introduced in some areas. These are short-stay facilities, available upon referral, targeted to help individuals who may be able to avoid an inpatient admission or lengthy ED visit. To advance knowledge about the effectiveness of this service for this purpose, we will examine the effect of the service on the mental health crisis care pathway over a 4-year time period; the 2 years proceeding and following the introduction of the service. We use aggregate service level data of key indicators of the performance of this pathway. Methods Data from four mental health Trusts in England will be analysed using an interrupted time series (ITS) design with the primary outcomes of the rate of (i) ED psychiatric presentations and (ii) voluntary admissions to mental health wards. This will be supplemented with a synthetic control study with the same primary outcomes, in which a comparable control group is generated for each outcome using a donor pool of suitable National Health Service Trusts in England. The methods are well suited to an evaluation of an intervention at a service delivery level targeting population-level health outcome and the randomisation or ‘trialability’ of the intervention is limited. The synthetic control study controls for national trends over time, increasing our confidence in the results. The study has been designed and will be carried out with the involvement of service users and carers. Discussion This will be the first formal evaluation of psychiatric decision units in England. The analysis will provide estimates of the effect of the decision units on a number of important service use indicators, providing much-needed information for those designing service pathways

Reducing vortex density in superconductors using the ratchet effect

A serious obstacle that impedes the application of low and high temperature superconductor (SC) devices is the presence of trapped flux. Flux lines or vortices are induced by fields as small as the Earth's magnetic field. Once present, vortices dissipate energy and generate internal noise, limiting the operation of numerous superconducting devices. Methods used to overcome this difficulty include the pinning of vortices by the incorporation of impurities and defects, the construction of flux dams, slots and holes and magnetic shields which block the penetration of new flux lines in the bulk of the SC or reduce the magnetic field in the immediate vicinity of the superconducting device. Naturally, the most desirable would be to remove the vortices from the bulk of the SC. There is no known phenomenon, however, that could form the basis for such a process. Here we show that the application of an ac current to a SC that is patterned with an asymmetric pinning potential can induce vortex motion whose direction is determined only by the asymmetry of the pattern. The mechanism responsible for this phenomenon is the so called ratchet effect, and its working principle applies to both low and high temperature SCs. As a first step here we demonstrate that with an appropriate choice of the pinning potential the ratchet effect can be used to remove vortices from low temperature SCs in the parameter range required for various applications.Comment: 7 pages, 4 figures, Nature (in press

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Combining motion analysis and microfluidics--a novel approach for detecting whole-animal responses to test substances.

Small, early life stages, such as zebrafish embryos are increasingly used to assess the biological effects of chemical compounds in vivo. However, behavioural screens of such organisms are challenging in terms of both data collection (culture techniques, drug delivery and imaging) and data evaluation (very large data sets), restricting the use of high throughput systems compared to in vitro assays. Here, we combine the use of a microfluidic flow-through culture system, or BioWell plate, with a novel motion analysis technique, (sparse optic flow - SOF) followed by spectral analysis (discrete Fourier transformation - DFT), as a first step towards automating data extraction and analysis for such screenings. Replicate zebrafish embryos housed in a BioWell plate within a custom-built imaging system were subject to a chemical exposure (1.5% ethanol). Embryo movement was videoed before (30 min), during (60 min) and after (60 min) exposure and SOF was then used to extract data on movement (angles of rotation and angular changes to the centre of mass of embryos). DFT was subsequently used to quantify the movement patterns exhibited during these periods and Multidimensional Scaling and ANOSIM were used to test for differences. Motion analysis revealed that zebrafish had significantly altered movements during both the second half of the alcohol exposure period and also the second half of the recovery period compared to their pre-treatment movements. Manual quantification of tail flicking revealed the same differences between exposure-periods as detected using the automated approach. However, the automated approach also incorporates other movements visible in the organism such as blood flow and heart beat, and has greater power to discern environmentally-driven changes in the behaviour and physiology of organisms. We suggest that combining these technologies could provide a highly efficient, high throughput assay, for assessing whole embryo responses to various drugs and chemicals

Decreased thermal tolerance under recurrent heat stress conditions explains summer mass mortality of the blue mussel Mytilus edulis

Extreme events such as heat waves have increased in frequency and duration over the last decades. Under future climate scenarios, these discrete climatic events are expected to become even more recurrent and severe. Heat waves are particularly important on rocky intertidal shores, one of the most thermally variable and stressful habitats on the planet. Intertidal mussels, such as the blue mussel Mytilus edulis, are ecosystem engineers of global ecological and economic importance, that occasionally suffer mass mortalities. This study investigates the potential causes and consequences of a mass mortality event of M. edulis that occurred along the French coast of the eastern English Channel in summer 2018. We used an integrative, climatological and ecophysiological methodology based on three complementary approaches. We first showed that the observed mass mortality (representing 49 to 59% of the annual commercial value of local recreational and professional fisheries combined) occurred under relatively moderate heat wave conditions. This result indicates that M. edulis body temperature is controlled by non-climatic heat sources instead of climatic heat sources, as previously reported for intertidal gastropods. Using biomimetic loggers (i.e. 'robomussels'), we identified four periods of 5 to 6 consecutive days when M. edulis body temperatures consistently reached more than 30 °C, and occasionally more than 35 °C and even more than 40 °C. We subsequently reproduced these body temperature patterns in the laboratory to infer M. edulis thermal tolerance under conditions of repeated heat stress. We found that thermal tolerance consistently decreased with the number of successive daily exposures. These results are discussed in the context of an era of global change where heat events are expected to increase in intensity and frequency, especially in the eastern English Channel where the low frequency of commercially exploitable mussels already questions both their ecological and commercial sustainability.Funding Agency French Ministere de l'Enseignement Superieur et de la Recherche Region Hauts-de-France European Funds for Regional Economical Development Pierre Hubert Curien PESSOA Felloswhip Fundacao para a Ciencia e Tecnologia (FCT-MEC, Portugal) IF/01413/2014/CP1217/CT0004 National Research Foundation - South Africa 64801 South African Research Chairs Initiative (SARChI) of the Department of Science and Technology National Research Foundation - South Africainfo:eu-repo/semantics/publishedVersio

Disease-associated missense mutations in GluN2B subunit alter NMDA receptor ligand binding and ion channel properties.

Genetic and bioinformatic analyses have identified missense mutations in GRIN2B encoding the NMDA receptor GluN2B subunit in autism, intellectual disability, Lennox Gastaut and West Syndromes. Here, we investigated several such mutations using a near-complete, hybrid 3D model of the human NMDAR and studied their consequences with kinetic modelling and electrophysiology. The mutants revealed reductions in glutamate potency; increased receptor desensitisation; and ablation of voltage-dependent Mg block. In addition, we provide new views on Mg and NMDA channel blocker binding sites. We demonstrate that these mutants have significant impact on excitatory transmission in developing neurons, revealing profound changes that could underlie their associated neurological disorders. Of note, the NMDAR channel mutant GluN2B unusually allowed Mg permeation, whereas nearby N615I reduced Ca permeability. By identifying the binding site for an NMDAR antagonist that is used in the clinic to rescue gain-of-function phenotypes, we show that drug binding may be modified by some GluN2B disease-causing mutations