Reducing the burden of hypoglycaemia in people with diabetes through increased understanding:design of the Hypoglycaemia Redefining Solutions for Better Lives (Hypo-RESOLVE) project

Background Hypoglycaemia is the most frequent complication of treatment with insulin or insulin secretagogues in people with diabetes. Severe hypoglycaemia, i.e. an event requiring external help because of cognitive dysfunction, is associated with a higher risk of adverse cardiovascular outcomes and all‐cause mortality, but underlying mechanism(s) are poorly understood. There is also a gap in the understanding of the clinical, psychological and health economic impact of ‘non‐severe’ hypoglycaemia and the glucose level below which hypoglycaemia causes harm. Aim To increase understanding of hypoglycaemia by addressing the above issues over a 4‐year period. Methods Hypo‐RESOLVE is structured across eight work packages, each with a distinct focus. We will construct a large, sustainable database including hypoglycaemia data from >100 clinical trials to examine predictors of hypoglycaemia and establish glucose threshold(s) below which hypoglycaemia constitutes a risk for adverse biomedical and psychological outcomes, and increases healthcare costs. We will also investigate the mechanism(s) underlying the antecedents and consequences of hypoglycaemia, the significance of glucose sensor‐detected hypoglycaemia, the impact of hypoglycaemia in families, and the costs of hypoglycaemia for healthcare systems. Results The outcomes of Hypo‐RESOLVE will inform evidence‐based definitions regarding the classification of hypoglycaemia in diabetes for use in daily clinical practice, future clinical trials and as a benchmark for comparing glucose‐lowering interventions and strategies across trials. Stakeholders will be engaged to achieve broadly adopted agreement. Conclusion Hypo‐RESOLVE will advance our understanding and refine the classification of hypoglycaemia, with the ultimate aim being to alleviate the burden and consequences of hypoglycaemia in people with diabetes

Using the Galileo Solid-State Imaging Instrument as a Sensor of Jovian Energetic Electrons

We quantitatively describe the Jovian energetic electron environment using the Solid State Imager (SSI) on the Galileo spacecraft. We post-process raw SSI images by removing the target object and dark current to obtain frames only with the radiation contribution. The camera settings (gain state, filter, etc.) are used to compute the energy deposited in each pixel, which corresponds to the intensity of the observed radiation hits (the actual measurements are expressed with the digital number (DN), from which the energy deposited can be computed). Histograms of the number of pixels versus energy deposited by incident particles from processed SSI images are compared with the results from 3D Monte Carlo transport simulations of the SSI using Geant4. We use Geant4 to simulate the response of the SSI instrument to mono-energetic electron environments from 1 to 100 MeV. We fit the modeled instrument response to the SSI data using a linear combination of the simulated mono-energetic histograms to match the SSI observations. We then estimate the spectra of the energetic electron environment at Jupiter, or we estimate the integral flux when there is lower confidence in the spectra fits. We validate the SSI results by comparing the environment predictions to the observations from the Energetic Particle Detector (EPD) on the Galileo spacecraft, examining the electron differential fluxes from 10’s of keV to 11 MeV. For higher energies (up to 31.0 MeV), we compare our findings with the NASA GIRE model, which is based on measurements from the Pioneer spacecraft. This approach could be applied to other sets of imaging data in energetic electron environments, such as from star trackers in geostationary Earth orbits.Funding for A. Carlton’s work is provided by a NASA Space Technology Research Fellowship (NNX16AM74H)

Ministerial directives to local government in Zimbabwe: top-down governance in a decentralized constitution

Urban and rural local authorities constitute the lowest tier of Zimbabwe's multilevel system of government. These local governments have a constitutional "right to govern" that must be exercised within the constitutional, legislative and policy framework. Under the old constitutional order, the national government could supervise urban local authorities, for example by issuing policy directives to ensure that these authorities governed in a manner that enabled them to deliver on national and local goals. This article examines this supervisory instrument, the powers it gives the national government, its use in practice and its relevance under the new constitutional order. The main argument is that supervisory instruments, such as the power to issue policy directives to local governments, are necessary in any multilevel system of government. However, such supervisory powers must be balanced with the need for local autonomy, to allow local governments to deliver on their service delivery obligations and development mandate.IS

The 2dF Galaxy Redshift Survey: a targeted study of catalogued clusters of galaxies

We have carried out a study of known clusters within the 2dF Galaxy Redshift Survey (2dFGRS) observed areas and have identified 431 Abell, 173APM and 343 EDCC clusters. Precise redshifts, velocity dispersions and new centroids have been measured for the majority of these objects, and this information is used to study the completeness of these catalogues, the level of contamination from foreground and background structures along the cluster's line of sight, the space density of the clusters as a function of redshift, and their velocity dispersion distributions. We find that the Abell and EDCC catalogues are contaminated at the level of about 10 per cent, whereas the APM catalogue suffers only 5 per cent contamination. If we use the original catalogue centroids, the level of contamination rises to approximately 15 per cent for the Abell and EDCC catalogues, showing that the presence of foreground and background groups may alter the richness of clusters in these catalogues. There is a deficiency of clusters at z~0.05 that may correspond to a large underdensity in the Southern hemisphere. From the cumulative distribution of velocity dispersions for these clusters, we derive a space density of σ>1000kms-1 clusters of 3.6×10-6h3Mpc-3. This result is used to constrain models for structure formation; our data favour low-density cosmologies, subject to the usual assumptions concerning the shape and normalization of the power spectrum

Amblyopia and quality of life: a systematic review

Background/Aims Amblyopia is a common condition which can affect up to 5% of the general population. The health-related quality of life (HRQoL) implications of amblyopia and/or its treatment have been explored in the literature. Methods A systematic literature search was undertaken (16th-30th January 2007) to identify the HRQoL implications of amblyopia and/or its treatment. Results A total of 25 papers were included in the literature review. The HRQoL implications of amblyopia related specifically to amblyopia treatment, rather than the condition itself. These included the impact upon family life; social interactions; difficulties undertaking daily activities; and feelings and behaviour. The identified studies adopted a number of methodologies. The study populations included; children with the condition; parents of children with amblyopia; and adults who had undertaken amblyopia treatment as a child. Some studies developed their own measures of HRQoL, and others determined HRQoL through proxy measures. Conclusions The reported findings of the HRQoL implications are of importance when considering the management of cases of amblyopia. Further research is required to assess the immediate and long-term effects of amblyopia and/or its treatment upon HRQoL using a more standardised approach

A Test for Radial Mixing Using Local Star Samples

We use samples of local main-sequence stars to show that the radial gradient of [Fe/H] in the thin disk of the Milky Way decreases with mean effective stellar temperature. Many of these stars are visiting the solar neighborhood from the inner and outer Galaxy. We use the angular momentum of each star about the Galactic center to determine the guiding center radius and to eliminate the effects of epicyclic motion, which would otherwise blur the estimated gradients. We interpret the effective temperature as a proxy for mean age, and conclude that the decreasing gradient is consistent with the predictions of radial mixing due to transient spiral patterns. We find some evidence that the trend of decreasing gradient with increasing mean age breaks to a constant gradient for samples of stars whose main-sequence life-times exceed the likely age of the thin disk.Comment: Accepted to appear in ApJ, 8 pages, 8 figure

Subjective probability and quantum certainty

In the Bayesian approach to quantum mechanics, probabilities--and thus quantum states--represent an agent's degrees of belief, rather than corresponding to objective properties of physical systems. In this paper we investigate the concept of certainty in quantum mechanics. Particularly, we show how the probability-1 predictions derived from pure quantum states highlight a fundamental difference between our Bayesian approach, on the one hand, and Copenhagen and similar interpretations on the other. We first review the main arguments for the general claim that probabilities always represent degrees of belief. We then argue that a quantum state prepared by some physical device always depends on an agent's prior beliefs, implying that the probability-1 predictions derived from that state also depend on the agent's prior beliefs. Quantum certainty is therefore always some agent's certainty. Conversely, if facts about an experimental setup could imply agent-independent certainty for a measurement outcome, as in many Copenhagen-like interpretations, that outcome would effectively correspond to a preexisting system property. The idea that measurement outcomes occurring with certainty correspond to preexisting system properties is, however, in conflict with locality. We emphasize this by giving a version of an argument of Stairs [A. Stairs, Phil. Sci. 50, 578 (1983)], which applies the Kochen-Specker theorem to an entangled bipartite system.Comment: 20 pages RevTeX, 1 figure, extensive changes in response to referees' comment

Hubble Space Telescope Evidence for an Intermediate-Mass Black Hole in the Globular Cluster M15: II. Kinematical Analysis and Dynamical Modeling

We analyze HST/STIS spectra (see Paper I) of the central region of the dense globular cluster M15. We infer the velocities of 64 individual stars, two-thirds of which have their velocity measured for the first time. This triples the number of stars with measured velocities in the central 1 arcsec of M15 and doubles the number in the central 2 arcsec. Combined with existing ground-based data we obtain the radial profiles of the projected kinematical quantities. The RMS velocity sigma_RMS rises to 14 km/s in the central few arcsec, somewhat higher than the values of 10-12 km/s inferred previously from ground-based data. To interpret the results we construct dynamical models based on the Jeans equation, which imply that M15 must have a central concentration of non-luminous material. If this is due to a single black hole, then its mass is M_BH = (3.9 +/- 2.2) x 10^3 solar masses. This is consistent with the relation between M_BH and sigma_RMS that has been established for galaxies. Also, the existence of intermediate-mass black holes in globular clusters is consistent with several scenarios for globular cluster evolution proposed in the literature. Therefore, these results may have important implications for our understanding of the evolution of globular clusters, the growth of black holes, the connection between globular cluster and galaxy formation, and the nature of the recently discovered `ultra-luminous' X-ray sources in nearby galaxies. Instead of a single black hole, M15 could have a central concentration of dark remnants (e.g., neutron stars) due to mass segregation. However, the best-fitting Fokker-Planck models that have previously been constructed for M15 do not predict a central mass concentration that is sufficient to explain the observed kinematics.[ABRIDGED]Comment: 43 pages, LaTeX, with 14 PostScript figures. Astronomical Journal, in press (Dec 2002). Please note that the results reported here are modified by the Addendum available at astro-ph/0210158 (Astronomical Journal, in press, Jan 2003). This second version submitted to astro-ph is identical to first, with the exception of the preceeding remar