Synthesis towards the antibiotic M139603

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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

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

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

Spectral signatures of reorganised brain networks in disorders of consciousness.

Theoretical advances in the science of consciousness have proposed that it is concomitant with balanced cortical integration and differentiation, enabled by efficient networks of information transfer across multiple scales. Here, we apply graph theory to compare key signatures of such networks in high-density electroencephalographic data from 32 patients with chronic disorders of consciousness, against normative data from healthy controls. Based on connectivity within canonical frequency bands, we found that patient networks had reduced local and global efficiency, and fewer hubs in the alpha band. We devised a novel topographical metric, termed modular span, which showed that the alpha network modules in patients were also spatially circumscribed, lacking the structured long-distance interactions commonly observed in the healthy controls. Importantly however, these differences between graph-theoretic metrics were partially reversed in delta and theta band networks, which were also significantly more similar to each other in patients than controls. Going further, we found that metrics of alpha network efficiency also correlated with the degree of behavioural awareness. Intriguingly, some patients in behaviourally unresponsive vegetative states who demonstrated evidence of covert awareness with functional neuroimaging stood out from this trend: they had alpha networks that were remarkably well preserved and similar to those observed in the controls. Taken together, our findings inform current understanding of disorders of consciousness by highlighting the distinctive brain networks that characterise them. In the significant minority of vegetative patients who follow commands in neuroimaging tests, they point to putative network mechanisms that could support cognitive function and consciousness despite profound behavioural impairment.This work was supported by grants from the Wellcome Trust [WT093811MA to T.B.]; the James S. McDonnell Foundation [to A.M.O. and J.D.P.]; the UK Medical Research Council [U.1055.01.002.00001.01 to A.M.O. and J.D.P.]; the Canada Excellence Research Chairs program [to A.M.O.]; the National Institute for Health Research Cambridge Biomedical Research Centre [to J.D.P.]; and the National Institute for Health Research Senior Investigator and Healthcare Technology Cooperative awards [to J.D.P.].This is the final version of the article. It first appeared from PLOS via http://dx.doi.org

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: 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

Multi-basin depositional framework for moisture-balance reconstruction during the last 1300 years at Lake Bogoria, central Kenya Rift Valley

Multi-proxy analysis of sediment cores from five key locations in hypersaline, alkaline Lake Bogoria (central Kenya Rift Valley) has allowed reconstruction of its history of depositional and hydrological change during the past 1300years. Analyses including organic matter and carbonate content, granulometry, mineralogical composition, charcoal counting and high-resolution scanning of magnetic susceptibility and elemental geochemistry resulted in a detailed sedimentological and compositional characterization of lacustrine deposits in the three lake basins and on the two sills separating them. Thesepalaeolimnological data were supplemented with information on present-day sedimentation conditions based on seasonal sampling of settling particles and on measurement of physicochemical profiles through the water column. A new age model based on Pb-210, Cs-137 and C-14 dating captures the sediment chronology of this hydrochemically complex and geothermally fed lake. An extensive set of chronological tie points between the equivalent high-resolution proxy time series of the five sediment sequences allowed transfer of radiometric dates between the basins, enabling interbasin comparison of sedimentation dynamics through time. The resulting reconstruction demonstrates considerable moisture-balance variability through time, reflecting regional hydroclimate dynamics over the past 1300years. Between ca 690 and 950AD, the central and southern basins of Lake Bogoria were reduced to shallow and separated brine pools. In the former, occasional near-complete desiccation triggered massive trona precipitation. Between ca 950 and 1100AD, slightly higher water levels allowed the build-up of high pCO(2) leading to precipitation of nahcolite still under strongly evaporative conditions. Lake Bogoria experienced a pronounced highstand between ca 1100 and 1350AD, only to recede again afterwards. For a substantial part of the time between ca 1350 and 1800AD, the northern basin was probably disconnected from the united central and southern basins. Throughout the last two centuries, lake level has been relatively high compared to the rest of the past millennium. Evidence for increased terrestrial sediment supply in recent decades, due to anthropogenic soil erosion in the wider Bogoria catchment, is a reason for concern about possible adverse impacts on the unique ecosystem of Lake Bogoria

Seeking order amidst chaos: a systematic review of classification systems for causes of stillbirth and neonatal death, 2009-2014.

BACKGROUND: Each year, about 5.3 million babies die in the perinatal period. Understanding of causes of death is critical for prevention, yet there is no globally acceptable classification system. Instead, many disparate systems have been developed and used. We aimed to identify all systems used or created between 2009 and 2014, with their key features, including extent of alignment with the International Classification of Diseases (ICD) and variation in features by region, to inform the World Health Organization's development of a new global approach to classifying perinatal deaths. METHODS: A systematic literature review (CINAHL, EMBASE, Medline, Global Health, and PubMed) identified published and unpublished studies and national reports describing new classification systems or modifications of existing systems for causes of perinatal death, or that used or tested such systems, between 2009 and 2014. Studies reporting ICD use only were excluded. Data were independently double-extracted (except from non-English publications). Subgroup analyses explored variation by extent and region. RESULTS: Eighty-one systems were identified as new, modifications of existing systems, or having been used between 2009 and 2014, with an average of ten systems created/modified each year. Systems had widely varying characteristics: (i) comprehensiveness (40 systems classified both stillbirths and neonatal deaths); (ii) extent of use (systems were created in 28 countries and used in 40; 17 were created for national use; 27 were widely used); (iii) accessibility (three systems available in e-format); (iv) underlying cause of death (64 systems required a single cause of death); (v) reliability (10 systems tested for reliability, with overall Kappa scores ranging from .35-.93); and (vi) ICD alignment (17 systems used ICD codes). Regional databases were not searched, so system numbers may be underestimated. Some non-differential misclassification of systems was possible. CONCLUSIONS: The plethora of systems in use, and continuing system development, hamper international efforts to improve understanding of causes of death. Recognition of the features of currently used systems, combined with a better understanding of the drivers of continued system creation, may help the development of a truly effective global system.The Mater Research Institute, University of Queensland, AustraliaThis is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s12884-016-1071-