3,272 research outputs found

    Thomas Hobbes\u27s Leviathan : A study in interpretation

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    Adverse childhood experiences and child mental health : an electronic birth cohort study

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    Acknowledgement We thank the SAIL databank for assisting in the statistical disclosure process. Declarations and Funding Data is collected routinely and access to this was granted via the SAIL databank. The corresponding author had full access to all the data in the study and final responsibility for the decision to submit for publication. The data sets generated and analysed during the current study are available in the SAIL databank repository, https://saildatabank.com/. This work was supported by funds from the Economic and Social Research Council, the Medical Research Council, and Alcohol Research UK to the ELAStiC Project (ESL015471/1) and Public Health Wales. The views expressed are those of the authors and should not be assumed to be of the funding body. The research was also supported by The Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement, a UK Clinical Research Collaboration Public Health Research Centre of Excellence. This work was supported by Health Data Research UK, which receives its funding from HDR UK Ltd (HDR-9006) funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation (BHF) and the Wellcome Trust. The funders had no role in designing the study, data collection, analysis, or interpretation, or in writing the report; MAB’s role in the design, analysis, and writing was independent of the funding from Public Health Wales. SP, SL and MAB had the original idea for this study. SP, AE, RA, EL and RD designed the study and developed the analysis plan. AJ provided advice on the mental health codes used in this analysis. AB extracted the data and prepared data sets for analysis. EM, AE and RA analysed the data. EM and RA wrote the first draft of the paper. All authors were involved in interpreting the findings, revising drafts and agreeing the final version.Peer reviewedPublisher PD

    Large-scale, high-density (up to 512 channels) recording of local circuits in behaving animals

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    Monitoring representative fractions of neurons from multiple brain circuits in behaving animals is necessary for understanding neuronal computation. Here we describe a system that allows high channel count recordings from a small volume of neuronal tissue using a lightweight signal multiplexing head-stage that permits free behavior of small rodents. The system integrates multi-shank, high-density recording silicon probes, ultra-flexible interconnects and a miniaturized microdrive. These improvements allowed for simultaneous recordings of local field potentials and unit activity from hundreds of sites without confining free movements of the animal. The advantages of large-scale recordings are illustrated by determining the electro-anatomical boundaries of layers and regions in the hippocampus and neocortex and constructing a circuit diagram of functional connections among neurons in real anatomical space. These methods will allow the investigation of circuit operations and behavior-dependent inter-regional interactions for testing hypotheses of neural networks and brain function

    Progress in marine geoconservation in Scotland’s seas : assessment of key interests and their contribution to Marine Protected Area network planning

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    This study was part-funded by Marine Scotland and was undertaken as part of the Scottish Marine Protected Areas (MPA) Programme, a joint initiative between Marine Scotland, Historic Scotland, Scottish Natural Heritage (SNH) and the Joint Nature Conservation Committee (JNCC).Geoconservation in the marine environment has been largely overlooked, despite a wealth of accumulated information on marine geology and geomorphology and clear links between many terrestrial and marine features. As part of the wider characterisation of Scotland’s seas, this study developed criteria and a methodology that follow the established principles of the terrestrial, Great Britain-wide geoconservation audit, the Geological Conservation Review, to assess geodiversity key areas on the seabed. Using an expert judgement approach, eight geodiversity feature categories were identified to represent the geological and geomorphological processes that have influenced the evolution and present-day morphology of the Scottish seabed: Quaternary of Scotland; Submarine Mass Movement; Marine Geomorphology of the Scottish Deep-Ocean Seabed; Seabed Fluid and Gas Seep; Cenozoic Structures of the Atlantic Margin; Marine Geomorphology of the Scottish Shelf Seabed; Coastal Geomorphology of Scotland; and Biogenic Structures of the Scottish Seabed. Within these categories, 35 key areas were prioritised for their scientific value. Specific interests range from large-scale landforms (e.g. submarine landslides, sea-mounts and trenches) to fine-scale dynamic features (e.g. sand waves). Although these geodiversity interests provided supporting evidence for the identification and selection of a suite of Nature Conservation Marine Protected Areas (MPAs) containing important marine natural features, they are only partially represented in these MPAs and existing protected areas. Nevertheless, a pragmatic approach is emerging to integrate as far as possible the conservation management of marine geodiversity with that of biodiversity and based on evidence of the sensitivity and vulnerability geological and geomorphological features on the seabed.PostprintPeer reviewe

    Neurocranial development of the coelacanth and the evolution of the sarcopterygian head

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    The neurocranium of sarcopterygian fishes was originally divided into an anterior (ethmosphenoid) and posterior (otoccipital) portion by an intracranial joint, and underwent major changes in its overall geometry before fusing into a single unit in lungfishes and early tetrapods. Although the pattern of these changes is well-documented, the developmental mechanisms that underpin variation in the form of the neurocranium and its associated soft tissues during the evolution of sarcopterygian fishes remain poorly understood. The coelacanth Latimeria is the only known living vertebrate that retains an intracranial joint. Despite its importance for understanding neurocranial evolution, the development of the neurocranium of this ovoviviparous fish remains unknown. Here we investigate the ontogeny of the neurocranium and brain in Latimeria chalumnae using conventional and synchrotron X-ray microcomputed tomography as well as magnetic resonance imaging, performed on an extensive growth series for this species. We describe the neurocranium at the earliest developmental stage known for Latimeria, as well as the major changes that the neurocranium undergoes during ontogeny. Changes in the neurocranium are associated with an extreme reduction in the relative size of the brain along with an enlargement of the notochord. The development of the notochord appears to have a major effect on the surrounding cranial components, and might underpin the formation of the intracranial joint. Our results shed light on the interplay between the neurocranium and its adjacent soft tissues during development in Latimeria, and provide insights into the developmental mechanisms that are likely to have underpinned the evolution of neurocranial diversity in sarcopterygian fishes

    Strong Fiber from Uniaxial Fullerene Supramolecules Aligned with Carbon Nanotubes

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    Carbon nanotube (CNT) wires approach copper's specific conductivity and surpass carbon fiber's strength, with further improvement anticipated with greater aspect ratios and incorporation of dopants with long-range structural order. Fullerenes assemble into multitudes of process-dependent supramolecular crystals and, while initially insulating, they become marginally conductive (up to 0.05 MSm1^{-1}) and superconductive (Tc=18T_c=18^\circK with K and 28^\circK with Rb) after doping. These were small (100's μ\mum long), soft (hardness comparable to indium), and typically unaligned, which hindered development of fullerene based wires. Individual fullerenes were previously incorporated into CNT fibers, although randomly without self-assembly into supramolecules. Here, a simple variation in established CNT acid extrusion creates a fiber composed of uniaxial chains of aligned fullerene supramolecules, self-assembled between aligned few-walled CNT bundles. This will provide a testbed for novel fullerene wire transport and prospects in CNT wire advancement

    Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study

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    The SCHOLAR-5 study examines treatment patterns and outcomes of real-world follicular lymphoma (FL) patients on 3rd line of treatment (LoT) or higher, for whom existing data are limited. SCHOLAR-5 is a retrospective cohort study using data from adults (≥ 18 years) with grade 1-3a FL, initiating ≥3rd LoT after June 2014 at major lymphoma centers in the United States (US) and Europe. Objective response rate (ORR), complete response (CR), progression free survival (PFS) and overall survival (OS) were analyzed by LoT. Time-to-event outcomes were assessed using Kaplan-Meier methods. Of 128 patients, 87 initiated 3rd LoT, 63 initiated 4th LoT, and 47 initiated 5th LoT. At 1st eligible LoT, 31% progressed within 24-months of 1st LoT anti-CD20 combination therapy, 28% had prior autologous stem-cell transplantation, and 31% were refractory to the previous LoT. The most common regimen in each LoT was chemoimmunotherapy; however, experimental drugs were increasingly used at later LoTs. In the US, anti-CD20 monotherapy was more common at ≥3rd LoT compared to Europe, where stem cell transplants were more common. ORR at 3rd LoT was 68% (CR 44%), but decreased after each LoT to 37% (CR 22%) in ≥5 LoT. Median OS and PFS at 3rd LoT were 68 and 11 months, respectively, and reduced to 43 and 4 months at ≥5 LoT. Treatments were heterogenous at each LoT in both the US and Europe. Few FL patients achieved complete response in later LoT, and duration of response and survival diminished with each subsequent line
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