Synthesis towards the antibiotic M139603

Imperial Users onl

An exact collisionless equilibrium for the force-free Harris sheet with low plasma beta

We present a first discussion and analysis of the physical properties of a new exact collisionless equilibrium for a one-dimensional nonlinear force-free magnetic field, namely, the force-free Harris sheet. The solution allows any value of the plasma beta, and crucially below unity, which previous nonlinear force-free collisionless equilibria could not. The distribution function involves infinite series of Hermite polynomials in the canonical momenta, of which the important mathematical properties of convergence and non-negativity have recently been proven. Plots of the distribution function are presented for the plasma beta modestly below unity, and we compare the shape of the distribution function in two of the velocity directions to a Maxwellian distribution

Collisionless current sheet equilibria

Current sheets are important for the structure and dynamics of many plasma systems. In space and astrophysical plasmas they play a crucial role in activity processes, for example by facilitating the release of magnetic energy via processes such as magnetic reconnection. In this contribution we will focus on collisionless plasma systems. A sensible first step in any investigation of physical processes involving current sheets is to find appropriate equilibrium solutions. The theory of collisionless plasma equilibria is well established, but over the past few years there has been a renewed interest in finding equilibrium distribution functions for collisionless current sheets with particular properties, for example for cases where the current density is parallel to the magnetic field (force-free current sheets). This interest is due to a combination of scientific curiosity and potential applications to space and astrophysical plasmas. In this paper we will give an overview of some of the recent developments, discuss their potential applications and address a number of open questions

Evidence-based decision support for pediatric rheumatology reduces diagnostic errors.

BACKGROUND: The number of trained specialists world-wide is insufficient to serve all children with pediatric rheumatologic disorders, even in the countries with robust medical resources. We evaluated the potential of diagnostic decision support software (DDSS) to alleviate this shortage by assessing the ability of such software to improve the diagnostic accuracy of non-specialists. METHODS: Using vignettes of actual clinical cases, clinician testers generated a differential diagnosis before and after using diagnostic decision support software. The evaluation used the SimulConsult® DDSS tool, based on Bayesian pattern matching with temporal onset of each finding in each disease. The tool covered 5405 diseases (averaging 22 findings per disease). Rheumatology content in the database was developed using both primary references and textbooks. The frequency, timing, age of onset and age of disappearance of findings, as well as their incidence, treatability, and heritability were taken into account in order to guide diagnostic decision making. These capabilities allowed key information such as pertinent negatives and evolution over time to be used in the computations. Efficacy was measured by comparing whether the correct condition was included in the differential diagnosis generated by clinicians before using the software ( unaided ), versus after use of the DDSS ( aided ). RESULTS: The 26 clinicians demonstrated a significant reduction in diagnostic errors following introduction of the software, from 28% errors while unaided to 15% using decision support (p \u3c 0.0001). Improvement was greatest for emergency medicine physicians (p = 0.013) and clinicians in practice for less than 10 years (p = 0.012). This error reduction occurred despite the fact that testers employed an open book approach to generate their initial lists of potential diagnoses, spending an average of 8.6 min using printed and electronic sources of medical information before using the diagnostic software. CONCLUSIONS: These findings suggest that decision support can reduce diagnostic errors and improve use of relevant information by generalists. Such assistance could potentially help relieve the shortage of experts in pediatric rheumatology and similarly underserved specialties by improving generalists\u27 ability to evaluate and diagnose patients presenting with musculoskeletal complaints. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02205086

The development of a space climatology: 3. Models of the evolution of distributions of space weather variables with timescale

We study how the probability distribution functions of power input to the magnetosphere Pα and of the geomagnetic ap and Dst indices vary with averaging timescale, , between 3 hours and 1 year. From this we develop and present algorithms to empirically model the distributions for a given and a given annual mean value. We show that lognormal distributions work well for ap, but because of the spread of Dst for low activity conditions, the optimum formulation for Dst leads to distributions better described by something like the Weibull formulation. Annual means can be estimated using telescope observations of sunspots and modelling, and so this allows the distributions to be estimated at any given between 3 hour and 1 year for any of the past 400 years, which is another important step towards a useful space weather climatology. The algorithms apply to the core of the distributions and can be used to predict the occurrence rate of “large” events (in the top 5% of activity levels): they may contain some, albeit limited, information relevant to characterizing the much rarer “superstorm” events with extreme value statistics. The algorithm for the Dst index is the more complex one because, unlike ap, Dst can take on either sign and future improvements to it are suggested

Patient preferences for topical treatment of actinic keratoses:a discrete-choice experiment

Funding: This study was funded by the National Institute for Health Research (NIHR) Research for Patient Benefit programme (PB-PG-0110-21244), Department of Health, UK. The funder was not involved in the study design. Acknowledgments: The authors gratefully acknowledge support from the Cancer Research UK Clinical Trials Unit, the UK Dermatology Clinical Trials Network, the NIHR Clinical Studies Group, and support for investigators from the British Skin Foundation and Cancer Research UK. We would also like to thank Martin Jones, Daniel Rigby and Ariel Bergmann for constructive comments on the design of the DCE.Peer reviewedPostprin

The development of a space climatology: 1. solar-wind magnetosphere coupling as a function of timescale and the effect of data gaps

Different terrestrial space weather indicators (such as geomagnetic indices, transpolar voltage, and ring current particle content) depend on different “coupling functions” (combinations of near-Earth solar wind parameters) and previous studies also reported a dependence on the averaging timescale, {\tau}. We study the relationships of the am and SME geomagnetic indices to the power input into the magnetosphere P_{\alpha}, estimated using the optimum coupling exponent {\alpha} for a range of {\tau} between 1 min and 1 year. The effect of missing data is investigated by introducing synthetic gaps into near-continuous data and the best method for dealing with them when deriving the coupling function, is formally defined. Using P_{\alpha}, we show that gaps in data recorded before 1995 have introduced considerable errors into coupling functions. From the near-continuous solar wind data for 1996-2016, we find {\alpha} = 0.44 plus/minus 0.02 and no significant evidence that {\alpha} depends on {\tau}, yielding P_{\alpha} = B^0.88 Vsw^1.90 (mswNsw)^0.23 sin4({\theta}/2), where B is the Interplanetary Magnetic Field (IMF), Nsw the solar wind number density, msw its mean ion mass, Vsw its velocity and {\theta} is the IMF clock angle in the Geocentric Solar Magnetospheric reference frame. Values of P_{\alpha} that are accurate to within plus/minus 5% for 1996-2016 have an availability of 83.8% and the correlation between P_{\alpha} and am for these data is shown to be 0.990 (between 0.972 and 0.997 at the 2{\sigma} uncertainty level), 0.897 plus/minus 0.004, and 0.790 plus/minus 0.03, for {\tau} of 1 year, 1 day and 3 hours, respectively, and that between P_{alpha} and SME at {\tau} of 1 min. is 0.7046 plus/minus 0.0004

The development of a space climatology: 2. The distribution of power input into the magnetosphere on a 3‐hourly timescale

Paper 1 in this series (Lockwood et al., 2018a, https://doi.org/10.1029/2018SW001856) showed that the power input into the magnetosphere Pα is an ideal coupling function for predicting geomagnetic “range” indices that are strongly dependent on the substorm current wedge and that the optimum coupling exponent α is 0.44 for all averaging timescales, τ, between 1 min and 1 year. The present paper explores the implications of these results. It is shown that the form of the distribution of Pα at all averaging timescales τ is set by the interplanetary magnetic field orientation factor via the nature of solar wind‐magnetosphere coupling (due to magnetic reconnection in the dayside magnetopause) and that at τ = 3 hr (the timescale of geomagnetic range indices) the normalized Pα (divided by its annual mean, that is, τ=3hr/τ=1yr) follows a Weibull distribution with k of 1.0625 and λ of 1.0240. This applies to all years to a useful degree of accuracy. It is shown that exploiting the constancy of this distribution and using annual means to predict the full distribution gives the probability of space weather events in the largest 10% and 5% to within uncertainties of magnitude 10% and 12%, respectively, at the one sigma level

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy

The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant

Uncharted waters: rare and unclassified cardiomyopathies characterized on cardiac magnetic resonance imaging

Cardiac magnetic resonance imaging (CMR) has undergone considerable technology advances in recent years, so that it is now entering into mainstream cardiac imaging practice. In particular, CMR is proving to be a valuable imaging tool in the detection, morphological assessment and functional assessment of cardiomyopathies. Although our understanding of this broad group of heart disorders continues to expand, it is an evolving group of entities, with the rarer cardiomyopathies remaining poorly understood or even unclassified. In this review, we describe the clinical and pathophysiological aspects of several of the rare/unclassified cardiomyopathies and their appearance on CMR