Net benefit approaches to the evaluation of prediction models, molecular markers, and diagnostic tests

Many decisions in medicine involve trade-offs, such as between diagnosing patients with disease versus unnecessary additional testing for those who are healthy. Net benefit is an increasingly reported decision analytic measure that puts benefits and harms on the same scale. This is achieved by specifying an exchange rate, a clinical judgment of the relative value of benefits (such as detecting a cancer) and harms (such as unnecessary biopsy) associated with models, markers, and tests. The exchange rate can be derived by asking simple questions, such as the maximum number of patients a doctor would recommend for biopsy to find one cancer. As the answers to these sorts of questions are subjective, it is possible to plot net benefit for a range of reasonable exchange rates in a "decision curve." For clinical prediction models, the exchange rate is related to the probability threshold to determine whether a patient is classified as being positive or negative for a disease. Net benefit is useful for determining whether basing clinical decisions on a model, marker, or test would do more good than harm. This is in contrast to traditional measures such as sensitivity, specificity, or area under the curve, which are statistical abstractions not directly informative about clinical value. Recent years have seen an increase in practical applications of net benefit analysis to research data. This is a welcome development, since decision analytic techniques are of particular value when the purpose of a model, marker, or test is to help doctors make better clinical decisions

Geophysical anomalies and quartz deformation of the Warburton West structure, central Australia

This paper reports geophysical anomalies and intra-crystalline quartz lamellae in drill cores from the Warburton West Basin overlapping the border of South Australia and the Northern Territory. The pre-Upper Carboniferous ~450×300km-large Warburton Basin, north-eastern South Australia, is marked by distinct eastern and western magnetic, gravity and low-velocity seismic tomography anomalies. Quartz grains from arenite core samples contain intra-crystalline lamellae in carbonate-quartz veins and in clastic grains, similar to those reported earlier from arenites, volcanic rocks and granites from the Warburton East Basin. Universal Stage measurements of quartz lamellae in both sub-basins define Miller-Bravais indices of {10-12} and {10-13}. In-situ quartz lamellae occur only in pre-Late Carboniferous rocks whereas lamellae-bearing clastic quartz grains occur in both pre-Late Carboniferous and post-Late Carboniferous rocks - the latter likely redeposited from the pre-Late Carboniferous basement. Quartz lamellae in clastic quartz grains are mostly curved and bent either due to tectonic deformation or to re-deformation of impact-generated planar features during crustal rebound or/and post-impact tectonic deformation. Seismic tomography low-velocity anomalies in both Warburton West Basin and Warburton East Basin suggest fracturing of the crust to depths of more than 20km. Geophysical modelling of the Cooper Basin, which overlies the eastern Warburton East Basin, suggests existence of a body of high-density (~2.9-3.0gr/cm) and high magnetic susceptibility (SI~0.012-0.037) at a depth of ~6-10km at the centre of the anomalies. In the Warburton West Basin a large magnetic body of SI=0.030 is modelled below ~10km, with a large positive gravity anomaly offset to the north of the magnetic anomaly. In both the Warburton East and Warburton West the deep crustal fracturing suggested by the low velocity seismic tomography complicates interpretations of the gravity data. Universal Stage measurements of quartz lamellae suggest presence of both planar deformation features of shock metamorphic derivation and deformed planar lamella. The latter may be attributed either to re-deformation of impact-generated lamella, impact rebound deformation or/and post impact tectonic deformation. The magnetic anomalies in the Warburton East and West sub-basins are interpreted in terms of (1) presence of deep seated central mafic bodies; (2) deep crustal fracturing and (3) removal of Devonian and Carboniferous strata associated with rebound of a central uplift consequent on large asteroid impact. Further tests of the Warburton structures require deep crustal seismic transects

Genetic and methylome variation in Turkish brachypodium distachyon accessions differentiate two geographically distinct subpopulations

Brachypodium distachyon (Brachypodium) is a non-domesticated model grass species that can be used to test if variation in genetic sequence or methylation are linked to environmental differences. To assess this, we collected seeds from 12 sites within five climatically distinct regions of Turkey. Seeds from each region were grown under standardized growth conditions in the UK to preserve methylated sequence variation. At six weeks following germination, leaves were sampled and assessed for genomic and DNA methylation variation. In a follow-up experiment, phenomic approaches were used to describe plant growth and drought responses. Genome sequencing and population structure analysis suggested three ancestral clusters across the Mediterranean, two of which were geographically separated in Turkey into coastal and central subpopulations. Phenotypic analyses showed that the coastal subpopulation tended to exhibit relatively delayed flowering and the central, increased drought tolerance as indicated by reduced yellowing. Genome-wide methylation analyses in GpC, CHG and CHH contexts also showed variation which aligned with the separation into coastal and central subpopulations. The climate niche modelling of both subpopulations showed a significant influence from the “Precipitation in the Driest Quarter” on the central subpopulation and “Temperature of the Coldest Month” on the coastal subpopulation. Our work demonstrates genetic diversity and variation in DNA methylation in Turkish accessions of Brachypodium that may be associated with climate variables and the molecular basis of which will feature in ongoing analyses. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.25; 2015/18/M/NZ2/00394; Horizon 2020 Framework Programme, H2020: 731013; Universität Zürich, UZHFunding: This research was funded by the National Science Centre Poland (grant no. 2015/18/M/NZ2/00394). Access to the National Plant Phenomics, Aberystwyth, UK was provided by the European Plant Phenotyping Network 2020 (“BRACHY-PHENO-DROUGHT” project, grant no. 25) and funded from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 731013. ACR and CS were supported by University Research Priority Program Evolution in Action of the University of Zurich. MW was supported by PSC Syngenta Fellowship.This research was funded by the National Science Centre Poland (grant no. 2015/18/M/NZ2/00394). Access to the National Plant Phenomics, Aberystwyth, UK was provided by the European Plant Phenotyping Network 2020 (?BRACHY-PHENO-DROUGHT? project, grant no. 25) and funded from the European Union?s Horizon 2020 research and innovation program under grant agreement no. 731013. ACR and CS were supported by University Research Priority Program Evolution in Action of the University of Zurich. MW was supported by PSC Syngenta Fellowship

The impact of community expectations on corporate community involvement disclosures in the UK

Despite increase mistrust between corporations and societies in the aftermath of the global corporate misbehaviours, the literature examining the impact of community concerns on corporate communications is undeveloped. Our paper is timely; it contributes to the literature on corporate social responsibility (CSR) by considering the impacts of community expectations on Corporate Community Involvement Disclosures (CCID) using a ten-year panel study. We advance CSR communication research by providing a fresh theoretical perspective – media-agenda-setting theory – to the broad CSR debate and the CCID subset of this debate. Our findings support the media-agenda theoretical expectation and provide important practice and policy recommendations for improving interactions between corporations and their communities

Who and when should we screen for prostate cancer? Interviews with key opinion leaders

Prostate cancer screening using prostate-specific antigen (PSA) is highly controversial. In this Q & A, Guest Editors for BMC Medicine's 'Spotlight on Prostate Cancer' article collection, Sigrid Carlsson and Andrew Vickers, invite some of the world's key opinion leaders to discuss who, and when, to screen for prostate cancer. In response to the points of view from the invited experts, the Guest Editors summarize the experts' views and give their own personal opinions on PSA screening

Electronic patient self-assessment and management (SAM): A novel framework for cancer survivorship

Background. We propose a novel framework for management of cancer survivorship: electronic patient Self-Assessment and Management (SAM). SAM is a framework for transfer of information to and from patients in such a way as to increase both the patient's and the health care provider's understanding of the patient's progress, and to help ensure that patient care follows best practice. Methods. Patients who participate in the SAM system are contacted by email at regular intervals and asked to complete validated questionnaires online. Patient responses on these questionnaires are then analyzed in order to provide patients with real-time, online information about their progress and to provide them with tailored and standardized medical advice. Patient-level data from the questionnaires are ported in real time to the patient's health care provider to be uploaded to clinic notes. An initial version of SAM has been developed at Memorial Sloan-Kettering Cancer Center (MSKCC) and the University of California, San Francisco (UCSF) for aiding the clinical management of patients after surgery for prostate cancer. Results. Pilot testing at MSKCC and UCSF suggests that implementation of SAM systems are feasible, with no major problems with compliance (> 70% response rate) or security. Conclusion. SAM is a conceptually simple framework for passing information to and from patients in such a way as to increase both the patient's and the health care provider's understanding of the patient's progress, and to help ensure that patient care follows best practice

How do you know if you are any good? A surgeon performance feedback system for the outcomes of radical prostatectomy

Surgery remains a mainstay of initial treatment for prostate cancer, with an estimated 85,000 operations per year in the US. Radical prostatectomy is associated with important risks of erectile dysfunction, urinary incontinence and, naturally, cancer recurrence. Given the possible consequences, it would be reassuring were it known that urologic surgeons offer uniformly high-quality care. Unfortunately, the data suggest that this is far from the case. There is copious evidence that surgeons with greater case volume or total lifetime experience have better outcomes. For example, low volume surgeons have complication rates 6 to 8% greater than their higher volume counterparts; in studies on the learning curve, the risk of recurrence is about 7% higher for a typical patient treated by an inexperienced surgeon than if treated by a more experienced surgeon There are also data that differences in outcome go over and above characteristics such as volume or experience, with large variations between surgeons even within volume categories, with one study reporting a five-fold variation in potency rates between surgeons at a single institution

Primary or secondary? A dichotomy of the strontium isotope anomalies in the Ediacaran carbonates of Saudi Arabia

Secular variation of 87Sr/86Sr in carbonate strata has been widely used in regional and global chemostratigraphic correlations. Typically, diagenesis results in higher 87Sr/86Sr signals relative to their primary composition due to the alteration by Rb-rich fluids and radiogenic decay of 87Rb to 87Sr. Surprisingly, 87Sr/86Sr values in the Ediacaran limestones from Saudi Arabia (from 0.7029 to 0.7059) are significantly lower than typical Ediacaran seawater values (mostly from 0.7080 to 0.7090) based on a global compilation. Understanding the origin of these anomalies is important insofar as early macrofossils are preserved in these strata. Two hypotheses have been independently evaluated in this study. The first hypothesis shows a low temperature scenario with isolated oceans or lakes in proximity to a mafic source. The second hypothesis is characterized by a high temperature scenario with profound overprints by juvenile hydrothermal fluids. Integrated Sr and Nd isotope data reveal that the 87Sr/86Sr anomalies are closely coupled with positive εNd(t = 560 Ma) values (up to +4.1). Clear covariations between 87Sr/86Sr, εNd, TOC, δ13Ccarb, δ13Corg, and δ18Ocarb were found. Based on multiple lines of petrographic, field, and geochemical evidence, the second hypothesis (i.e., hydrothermal alteration by juvenile fluids) is preferred in this study. Thermogenic breakdown of organic matter in host sediments may have caused the increasingly low TOC abundance and high δ13Corg signals of the residual organic matter. We argue that the concept that the Ediacaran biotic radiation took place in an isolated lake environment should be treated with caution. These remarkably low 87Sr/86Sr signals have neither temporal nor biogeochemical significance. Sr isotope chemostratigraphy in this particular region may not be a reliable tool for stratigraphic correlations

Propagation of leaky MHD waves at discontinuities with tilted magnetic field

We investigate the characteristics of magneto-acoustic surface waves propagating at a single density interface, in the presence of an inclined magnetic field. For linear wave propagation, the dispersion relation is obtained and analytical solutions are derived for small inclination angle. The inclination of the field renders the frequency of the waves complex, where the imaginary part describes wave attenuation, due to lateral energy leakage