Ceres' opposition effect observed by the Dawn framing camera

The surface reflectance of planetary regoliths may increase dramatically towards zero phase angle, a phenomenon known as the opposition effect (OE). Two physical processes that are thought to be the dominant contributors to the brightness surge are shadow hiding (SH) and coherent backscatter (CB). The occurrence of shadow hiding in planetary regoliths is self-evident, but it has proved difficult to unambiguously demonstrate CB from remote sensing observations. One prediction of CB theory is the wavelength dependence of the OE angular width. The Dawn spacecraft observed the OE on the surface of dwarf planet Ceres. We characterize the OE over the resolved surface, including the bright Cerealia Facula, and to find evidence for SH and/or CB. We analyze images of the Dawn framing camera by means of photometric modeling of the phase curve. We find that the OE of most of the investigated surface has very similar characteristics, with an enhancement factor of 1.4 and a FWHM of 3{\deg} (broad OE). A notable exception are the fresh ejecta of the Azacca crater, which display a very narrow brightness enhancement that is restricted to phase angles $< 0.5${\deg} (narrow OE); suggestively, this is in the range in which CB is thought to dominate. We do not find a wavelength dependence for the width of the broad OE, and lack the data to investigate the dependence for the narrow OE. The prediction of a wavelength-dependent CB width is rather ambiguous. The zero-phase observations allow us to determine Ceres' visible geometric albedo as $p_V = 0.094 \pm 0.005$. A comparison with other asteroids suggests that Ceres' broad OE is typical for an asteroid of its spectral type, with characteristics that are primarily linked to surface albedo. Our analysis suggests that CB may occur on the dark surface of Ceres in a highly localized fashion.Comment: Credit: Schr\"oder et al, A&A in press, 2018, reproduced with permission, \copyright ES

A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings

BackgroundA composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data.MethodsWe assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation.ResultsThe analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals.ConclusionThe GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Impact and therapy of osteoarthritis: the Arthritis Care OA Nation 2012 survey

Osteoarthritis (OA) is the fastest growing cause of disability worldwide. The aim of this study was to understand the impact of OA on individuals and to explore current treatment strategies. An online UK-wide survey of people with self-reported OA was conducted, composed of 52 questions exploring the impact of OA, diagnosis and treatment, the role of health professionals and self-management. Four thousand forty-three people were invited with 2,001 respondents (49 % response, 56 % women; mean age 65 years). Fifty-two percent reported that OA had a large impact on their lives. Fifteen percent of respondents had taken early retirement on average 7.8 years earlier than planned. In consultations with general practitioners, only half reported a discussion on pain; fewer reported discussing their fears (21 %) or management goals (15 %). Nearly half (48 %) reported not seeking medical help until pain was frequently unbearable. Oral analgesics (62 %), topical therapies (47 %), physiotherapy (38 %) and steroid injections (28 %) were commonly used. The majority (71 %) reported varying degrees of persistent pain despite taking all prescribed medication. Although 64 % knew that increasing exercise was important, only 36 % acted on this knowledge; 87 % who increased exercise found it beneficial. Over half had future concerns related to mobility (60 %), maintaining independence (52 %) and coping with everyday activities (51 %). OA had significant individual economic impact especially on employment. Current treatment strategies still leave most people in pain with significant fears for the future. There is considerable opportunity to improve the holistic nature of OA consultations especially in provision of information and promotion of self-management strategies