We present experimental results from the first systematic study of performance scaling with drive parameters for a magnetoinertial fusion concept. In magnetized liner inertial fusion experiments, the ...burn-averaged ion temperature doubles to 3.1 keV and the primary deuterium-deuterium neutron yield increases by more than an order of magnitude to 1.1 × 1013 (2 kJ deuterium-tritium equivalent) through a simultaneous increase in the applied magnetic field (from 10.4 to 15.9 T), laser preheat energy (from 0.46 to 1.2 kJ), and current coupling (from 16 to 20 MA). Individual parametric scans of the initial magnetic field and laser preheat energy show the expected trends, demonstrating the importance of magnetic insulation and the impact of the Nernst effect for this concept. A drive-current scan shows that present experiments operate close to the point where implosion stability is a limiting factor in performance, demonstrating the need to raise fuel pressure as drive current is increased. Simulations that capture these experimental trends indicate that another order of magnitude increase in yield on the Z facility is possible with additional increases of input parameters.
The current CONSORT guidelines for reporting pilot trials do not recommend hypothesis testing of clinical outcomes on the basis that a pilot trial is under-powered to detect such differences and this ...is the aim of the main trial. It states that primary evaluation should focus on descriptive analysis of feasibility/process outcomes (e.g. recruitment, adherence, treatment fidelity). Whilst the argument for not testing clinical outcomes is justifiable, the same does not necessarily apply to feasibility/process outcomes, where differences may be large and detectable with small samples. Moreover, there remains much ambiguity around sample size for pilot trials.
Many pilot trials adopt a 'traffic light' system for evaluating progression to the main trial determined by a set of criteria set up a priori. We construct a hypothesis testing approach for binary feasibility outcomes focused around this system that tests against being in the RED zone (unacceptable outcome) based on an expectation of being in the GREEN zone (acceptable outcome) and choose the sample size to give high power to reject being in the RED zone if the GREEN zone holds true. Pilot point estimates falling in the RED zone will be statistically non-significant and in the GREEN zone will be significant; the AMBER zone designates potentially acceptable outcome and statistical tests may be significant or non-significant.
For example, in relation to treatment fidelity, if we assume the upper boundary of the RED zone is 50% and the lower boundary of the GREEN zone is 75% (designating unacceptable and acceptable treatment fidelity, respectively), the sample size required for analysis given 90% power and one-sided 5% alpha would be around n = 34 (intervention group alone). Observed treatment fidelity in the range of 0-17 participants (0-50%) will fall into the RED zone and be statistically non-significant, 18-25 (51-74%) fall into AMBER and may or may not be significant and 26-34 (75-100%) fall into GREEN and will be significant indicating acceptable fidelity.
In general, several key process outcomes are assessed for progression to a main trial; a composite approach would require appraising the rules of progression across all these outcomes. This methodology provides a formal framework for hypothesis testing and sample size indication around process outcome evaluation for pilot RCTs.
Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, ...complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.
Objectives
To assess the performance of clinical risk factors, uterine artery Doppler and angiogenic markers to predict preterm pre‐eclampsia in nulliparous women.
Design
Predictive test accuracy ...study.
Setting
Prospective multicentre cohort study Screening for Pregnancy Endpoints (SCOPE).
Methods
Low‐risk nulliparous women with a singleton pregnancy were recruited. Clinical risk factor data were obtained and plasma placental growth factor (PlGF), soluble endoglin and soluble fms‐like tyrosine kinase‐1 (sFlt‐1) were measured at 14–16 weeks of gestation. Prediction models were developed using multivariable stepwise logistic regression.
Main outcome measure
Preterm pre‐eclampsia (delivered before 37+0 weeks of gestation).
Results
Of the 3529 women recruited, 187 (5.3%) developed pre‐eclampsia of whom 47 (1.3%) delivered preterm. Controls (n = 188) were randomly selected from women without preterm pre‐eclampsia and included women who developed other pregnancy complications. An area under a receiver operating characteristic curve (AUC) of 0.76 (95% CI 0.67–0.84) was observed using previously reported clinical risk variables. The AUC improved following the addition of PlGF measured at 14–16 weeks (0.84; 95% CI 0.77–0.91), but no further improvement was observed with the addition of uterine artery Doppler or the other angiogenic markers. A sensitivity of 45% (95% CI 0.31–0.59) (5% false‐positive rate) and post‐test probability of 11% (95% CI 9–13) were observed using clinical risk variables and PlGF measurement.
Conclusions
Addition of plasma PlGF at 14–16 weeks of gestation to clinical risk assessment improved the identification of nulliparous women at increased risk of developing preterm pre‐eclampsia, but the performance is not sufficient to warrant introduction as a clinical screening test. These findings are marker dependent, not assay dependent; additional markers are needed to achieve clinical utility.
We present recent results from the initial testing of an artificial neural network (ANN)-based tomographic reconstructor Complex Atmospheric Reconstructor based on Machine lEarNing (CARMEN) on ...CANARY, an adaptive optics demonstrator operated on the 4.2 m William Herschel Telescope, La Palma. The reconstructor was compared with contemporaneous data using the Learn and Apply (L&A) tomographic reconstructor. We find that the fully optimized L&A tomographic reconstructor outperforms CARMEN by approximately 5 per cent in Strehl ratio or 15 nm rms in wavefront error. We also present results for CANARY in Ground Layer Adaptive Optics mode to show that the reconstructors are tomographic. The results are comparable and this small deficit is attributed to limitations in the training data used to build the ANN. Laboratory bench tests show that the ANN can outperform L&A under certain conditions, e.g. if the higher layer of a model two layer atmosphere was to change in altitude by ∼300 m (equivalent to a shift of approximately one tenth of a subaperture).
We present the first experimental study of plasmoid formation in a magnetic reconnection layer undergoing rapid radiative cooling, a regime relevant to extreme astrophysical plasmas. Two exploding ...aluminum wire arrays, driven by the Z machine, generate a reconnection layer (S_{L}≈120) in which the cooling rate far exceeds the hydrodynamic transit rate (τ_{hydro}/τ_{cool}>100). The reconnection layer generates a transient burst of >1 keV x-ray emission, consistent with the formation and subsequent rapid cooling of the layer. Time-gated x-ray images show fast-moving (up to 50 km s^{-1}) hotspots in the layer, consistent with the presence of plasmoids in 3D resistive magnetohydrodynamic simulations. X-ray spectroscopy shows that these hotspots generate the majority of Al K-shell emission (around 1.6 keV) prior to the onset of cooling, and exhibit temperatures (170 eV) much greater than that of the plasma inflows and the rest of the reconnection layer, thus providing insight into the generation of high-energy radiation in radiatively cooled reconnection events.
Abstract
The Durham adaptive optics real-time controller is a generic, high-performance real-time control system for astronomical adaptive optics systems. It has recently had new features added as ...well as performance improvements, and here we give details of these, as well as ways in which optimizations can be made for specific adaptive optics systems and hardware implementations. We also present new measurements that show how this real-time control system could be used with any existing adaptive optics system, and also show that when used with modern hardware, it has high enough performance to be used with most Extremely Large Telescope adaptive optics systems.
Warmer temperatures are accelerating the phenology of organisms around the world. Temperature sensitivity of phenology might be greater in colder, higher latitude sites than in warmer regions, in ...part because small changes in temperature constitute greater relative changes in thermal balance at colder sites. To test this hypothesis, we examined up to 20 years of phenology data for 47 tundra plant species at 18 high‐latitude sites along a climatic gradient. Across all species, the timing of leaf emergence and flowering was more sensitive to a given increase in summer temperature at colder than warmer high‐latitude locations. A similar pattern was seen over time for the flowering phenology of a widespread species, Cassiope tetragona. These are among the first results highlighting differential phenological responses of plants across a climatic gradient and suggest the possibility of convergence in flowering times and therefore an increase in gene flow across latitudes as the climate warms.
Warmer temperatures are accelerating the phenology of organisms around the world, and temperature sensitivity of phenology might be greater in colder, higher latitude sites than in warmer regions. We tested this hypothesis using phenology data for 47 tundra plant species at 18 high‐latitude sites along a climatic gradient. Across all species, the timing of leaf emergence and flowering was more sensitive to a given increase in summer temperature at colder than warmer high‐latitude locations. These are among the first results highlighting differential phenological responses of plants across a climatic gradient and suggest the possibility of convergence in flowering times and therefore an increase in gene flow across latitudes as the climate warms. (Photo credit: Anne D. Bjorkman)
Treatment with teriparatide (rDNA origin) injection {teriparatide, recombinant human parathyroid hormone (1–34) rhPTH(1–34)}reduces the risk of vertebral and nonvertebral fragility fractures and ...increases cancellous bone mineral density in postmenopausal women with osteoporosis, but its effects on cortical bone are less well established. This cross‐sectional study assessed parameters of cortical bone quality by peripheral quantitative computed tomography (pQCT) in the nondominant distal radius of 101 postmenopausal women with osteoporosis who were randomly allocated to once‐daily, self‐administered subcutaneous injections of placebo (n = 35) or teriparatide 20 μg (n = 38) or 40 μg (n = 28). We obtained measurements of moments of inertia, bone circumferences, bone mineral content, and bone area after a median of 18 months of treatment. The results were adjusted for age, height, and weight. Compared with placebo, patients treated with teriparatide 40 μg had significantly higher total bone mineral content, total and cortical bone areas, periosteal and endocortical circumferences, and axial and polar cross‐sectional moments of inertia. Total bone mineral content, total and cortical bone areas, periosteal circumference, and polar cross‐sectional moment of inertia were also significantly higher in the patients treated with teriparatide 20 μg compared with placebo. There were no differences in total bone mineral density, cortical thickness, cortical bone mineral density, or cortical bone mineral content among groups. In summary, once‐daily administration of teriparatide induced beneficial changes in the structural architecture of the distal radial diaphysis consistent with increased mechanical strength without adverse effects on total bone mineral density or cortical bone mineral content.
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