723 research outputs found

    Investigating radiatively driven, magnetized plasmas with a university scale pulsed-power generator

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    We present first results from a novel experimental platform which is able to access physics relevant to topics including indirect-drive magnetised ICF; laser energy deposition; various topics in atomic physics; and laboratory astrophysics (for example the penetration of B-fields into HED plasmas). This platform uses the X-Rays from a wire array Z-Pinch to irradiate a silicon target, producing an outflow of ablated plasma. The ablated plasma expands into ambient, dynamically significant B-fields (~5 T) which are supported by the current flowing through the Z-Pinch. The outflows have a well-defined (quasi-1D) morphology, enabling the study of fundamental processes typically only available in more complex, integrated schemes. Experiments were fielded on the MAGPIE pulsed-power generator (1.4 MA, 240 ns rise time). On this machine a wire array Z-Pinch produces an X-Ray pulse carrying a total energy of ~15 kJ over ~30 ns. This equates to an average brightness temperature of around 10 eV on-target

    SWATH mass spectrometry as a tool for quantitative profiling of the matrisome.

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    Proteomic analysis of extracellular matrix (ECM) and ECM-associated proteins, collectively known as the matrisome, is a challenging task due to the inherent complexity and insolubility of these proteins. Here we present sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH MS) as a tool for the quantitative analysis of matrisomal proteins in both non-enriched and ECM enriched tissue without the need for prior fractionation. Utilising a spectral library containing 201 matrisomal proteins, we compared the performance and reproducibility of SWATH MS over conventional data-dependent analysis mass spectrometry (DDA MS) in unfractionated murine lung and liver. SWATH MS conferred a 15-20% increase in reproducible peptide identification across replicate experiments in both tissue types and identified 54% more matrisomal proteins in the liver versus DDA MS. We further use SWATH MS to evaluate the quantitative changes in matrisome content that accompanies ECM enrichment. Our data shows that ECM enrichment led to a systematic increase in core matrisomal proteins but resulted in significant losses in matrisome-associated proteins including the cathepsins and proteins of the S100 family. Our proof-of-principle study demonstrates the utility of SWATH MS as a versatile tool for in-depth characterisation of the matrisome in unfractionated and non-enriched tissues. SIGNIFICANCE: The matrisome is a complex network of extracellular matrix (ECM) and ECM-associated proteins that provides scaffolding function to tissues and plays important roles in the regulation of fundamental cellular processes. However, due to its inherent complexity and insolubility, proteomic studies of the matrisome typically require the application of enrichment workflows prior to MS analysis. Such enrichment strategies often lead to losses in soluble matrisome-associated components. In this study, we present sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH MS) as a tool for the quantitative analysis of matrisomal proteins. We show that SWATH MS provides a more reproducible coverage of the matrisome compared to data-dependent analysis (DDA) MS. We also demonstrate that SWATH MS is capable of accurate quantification of matrisomal proteins without prior ECM enrichment and fractionation, which may simplify sample handling workflows and avoid losses in matrisome-associated proteins commonly linked to ECM enrichment

    Extracellular ascorbate modulates glutamate dynamics: role of behavioral activation

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    <p>Abstract</p> <p>Background</p> <p>A physiological increase in extracellular ascorbate (AA), an antioxidant vitamin found throughout the striatum, elevates extracellular glutamate (GLU). To determine the role of behavioral arousal in this interaction, microdialysis was used to measure striatal GLU efflux in rats tested in either a lights-off or lights-on condition while reverse dialysis either maintained the concentration of AA at 250 μM or increased it to 1000 μM to approximate endogenous changes.</p> <p>Results</p> <p>When lights were off, both locomotion and GLU increased regardless of AA dose. In contrast, animals in the lights-on condition were behaviorally inactive, and infusion of 1000, but not 250, μM AA significantly increased extracellular GLU. Interestingly, when ambient light returned to the lights-off group, 1000 μM prolonged the GLU increase relative to the 250 μM group.</p> <p>Conclusion</p> <p>Our results not only support evidence that elevated striatal AA increases extracellular GLU but also indicate that this effect depends on behavioral state and the corresponding level of endogenous GLU release.</p

    The course of untreated anxiety and depression, and determinants of poor one-year outcome: a one-year cohort study

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    <p>Abstract</p> <p>Background</p> <p>Little is known about the course and outcome of untreated anxiety and depression in patients with and without a self-perceived need for care. The aim of the present study was to examine the one-year course of untreated anxiety and depression, and to determine predictors of a poor outcome.</p> <p>Method</p> <p>Baseline and one-year follow-up data were used of 594 primary care patients with current anxiety or depressive disorders at baseline (established by the Composite Interview Diagnostic Instrument (CIDI)), from the Netherlands Study of Depression and Anxiety (NESDA). Receipt of and need for care were assessed by the Perceived Need for Care Questionnaire (PNCQ).</p> <p>Results</p> <p>In depression, treated and untreated patients with a perceived treatment need showed more rapid symptom decline but greater symptom severity at follow-up than untreated patients without a self-perceived mental problem or treatment need. A lower education level, lower income, unemployment, loneliness, less social support, perceived need for care, number of somatic disorders, a comorbid anxiety and depressive disorder and symptom severity at baseline predicted a poorer outcome in both anxiety and depression. When all variables were considered at the same time, only baseline symptom severity appeared to predict a poorer outcome in anxiety. In depression, a poorer outcome was also predicted by more loneliness and a comorbid anxiety and depressive disorder.</p> <p>Conclusion</p> <p>In clinical practice, special attention should be paid to exploring the need for care among possible risk groups (e.g. low social economic status, low social support), and support them in making an informed decision on whether or not to seek treatment.</p

    Psychopathology in Dutch young adults: enduring or changeable?

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    This study reports on stability and change in emotional and behavioral problems in young adults over a 2-year time span. A sample of 528 18- to 22-year-olds from the general population was assessed using the Young Adult Self-Report (YASR) on two occasions. Stability coefficients for the total problem score of the YASR were 0.63 for males and 0.75 for females. Forty-nine percent of the subjects who were initially classified as deviant were still deviant at follow-up. Of all YASR syndromes, the highest stability was for the Anxious/Depressed scale

    Screening and brief interventions for hazardous and harmful alcohol use in primary care: a cluster randomised controlled trial protocol

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    A large number of randomised controlled trials in health settings have consistently reported positive effects of brief intervention in terms of reductions in alcohol use. However,although alcohol misuse is common amongst offenders, there is limited evidence of alcohol brief interventions in the criminal justice field. This factorial pragmatic cluster randomised controlledtrial with Offender Managers (OMs) as the unit of randomisation will evaluate the effectiveness and cost-effectiveness of different models of screening to identify hazardous and harmful drinkers in probation and different intensities of brief intervention to reduce excessive drinking in probation clients. Ninety-six OMs from 9 probation areas across 3 English regions (the NorthEast Region (n = 4) and London and the South East Regions (n = 5)) will be recruited. OMs will berandomly allocated to one of three intervention conditions: a client information leaflet control condition (n = 32 OMs); 5-minute simple structured advice (n = 32 OMs) and 20-minute brieflifestyle counselling delivered by an Alcohol Health Worker (n = 32 OMs). Randomisation will be stratified by probation area. To test the relative effectiveness of different screening methods all OMs will be randomised to either the Modified Single Item Screening Questionnaire (M-SASQ) orthe Fast Alcohol Screening Test (FAST). There will be a minimum of 480 clients recruited into the trial. There will be an intention to treat analysis of study outcomes at 6 and 12 months postintervention. Analysis will include client measures (screening result, weekly alcohol consumption,alcohol-related problems, re-offending, public service use and quality of life) and implementation measures from OMs (the extent of screening and brief intervention beyond the minimum recruitment threshold will provide data on acceptability and feasibility of different models of brief intervention). We will also examine the practitioner and organisational factors associated with successful implementation.The trial will evaluate the impact of screening and brief alcohol intervention in routine probation work and therefore its findings will be highly relevant to probation teams and thus the criminal justice system in the UK

    Measurements of knee rotation-reliability of an external device in vivo

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    <p>Abstract</p> <p>Background</p> <p>Knee rotation plays an important part in knee kinematics during weight-bearing activities. An external device for measuring knee rotation (the Rottometer) has previously been evaluated for validity by simultaneous measurements of skeletal movements with Roentgen Stereometric Analysis (RSA). The aim of this study was to investigate the reliability of the device.</p> <p>Method</p> <p>The within-day and test-retest reliability as well as intertester reliability of the device in vivo was calculated. Torques of 3, 6 and 9 Nm and the examiner's apprehension of end-feel were used at 90°, 60° and 30° of knee flexion. Intraclass Correlation Coefficient <sub>2,1 </sub>(ICC <sub>2,1</sub>), 95% confidence interval (CI) of ICC and 95% CI between test trials and examiners were used as statistical tests.</p> <p>Result</p> <p>ICC<sub>2,1 </sub>ranged from 0.50 to 0.94 at all three flexion angles at 6 and 9 Nm as well as end-feel, and from 0.22 to 0.75 at 3 Nm applied torque.</p> <p>Conclusion</p> <p>The Rottometer was a reliable measurement instrument concerning knee rotation at the three different flexion angles (90°, 60° and 30°) with 6 and 9 Nm applied torques as well as the examiner's apprehension of end-feel. Three Nm was not a reliable torque. The most reliable measurements were made at 9 Nm applied torque.</p

    Near-identical star formation rate densities from Hα and FUV at redshift zero

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    For the first time both Hα\alpha and far-ultraviolet (FUV) observations from an HI-selected sample are used to determine the dust-corrected star formation rate density (SFRD: ρ˙\dot{\rho}) in the local Universe. Applying the two star formation rate indicators on 294 local galaxies we determine log(ρ˙\dot{\rho}Hα)=1.68 0.05+0.13 _{H\alpha}) = -1.68~^{+0.13}_{-0.05} [M_{\odot} yr1^{-1} Mpc3]^{-3}] and log(ρ˙FUV\dot{\rho}_{FUV}) =1.71 0.13+0.12 = -1.71~^{+0.12}_{-0.13} [M_\odot yr1^{-1} Mpc3]^{-3}]. These values are derived from scaling Hα\alpha and FUV observations to the HI mass function. Galaxies were selected to uniformly sample the full HI mass (MHI_{HI}) range of the HI Parkes All-Sky Survey (MHI107_{HI} \sim10^{7} to 1010.7\sim10^{10.7} M_{\odot}). The approach leads to relatively larger sampling of dwarf galaxies compared to optically-selected surveys. The low HI mass, low luminosity and low surface brightness galaxy populations have, on average, lower Hα\alpha/FUV flux ratios than the remaining galaxy populations, consistent with the earlier results of Meurer. The near-identical Hα\alpha- and FUV-derived SFRD values arise with the low Hα\alpha/FUV flux ratios of some galaxies being offset by enhanced Hα\alpha from the brightest and high mass galaxy populations. Our findings confirm the necessity to fully sample the HI mass range for a complete census of local star formation to include lower stellar mass galaxies which dominate the local Universe.Partial funding for the SINGG and SUNGG surveys came from NASA grants NAG5-13083 (LTSA program), GALEX GI04- 0105-0009 (NASA GALEX Guest Investigator grant) and NNX09AF85G (GALEX archival grant) to G.R. Meurer. FAR acknowledges partial funding from the Department of Physics, University of Western Australia. This research has made use of the NASA/IPAC Extragalactic Database (NED), which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration

    Using simulation to interpret a discrete time survival model in a complex biological system: fertility and lameness in dairy cows

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    The ever-growing volume of data routinely collected and stored in everyday life presents researchers with a number of opportunities to gain insight and make predictions. This study aimed to demonstrate the usefulness in a specific clinical context of a simulation-based technique called probabilistic sensitivity analysis (PSA) in interpreting the results of a discrete time survival model based on a large dataset of routinely collected dairy herd management data. Data from 12,515 dairy cows (from 39 herds) were used to construct a multilevel discrete time survival model in which the outcome was the probability of a cow becoming pregnant during a given two day period of risk, and presence or absence of a recorded lameness event during various time frames relative to the risk period amongst the potential explanatory variables. A separate simulation model was then constructed to evaluate the wider clinical implications of the model results (i.e. the potential for a herd’s incidence rate of lameness to influence its overall reproductive performance) using PSA. Although the discrete time survival analysis revealed some relatively large associations between lameness events and risk of pregnancy (for example, occurrence of a lameness case within 14 days of a risk period was associated with a 25% reduction in the risk of the cow becoming pregnant during that risk period), PSA revealed that, when viewed in the context of a realistic clinical situation, a herd’s lameness incidence rate is highly unlikely to influence its overall reproductive performance to a meaningful extent in the vast majority of situations. Construction of a simulation model within a PSA framework proved to be a very useful additional step to aid contextualisation of the results from a discrete time survival model, especially where the research is designed to guide on-farm management decisions at population (i.e. herd) rather than individual level
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