68 research outputs found
Characterizing galaxy clusters by their gravitational potential: systematics of cluster potential reconstruction
Context. Biases in mass measurements of galaxy clusters are one of the major
limiting systematics in constraining cosmology with clusters. Aims. We aim to
demonstrate that the systematics associated with cluster gravitational
potentials are smaller than the hydrostatic mass bias and that cluster
potentials could therefore be a good alternative to cluster masses in
cosmological studies. Methods. Using cosmological simulations of galaxy
clusters, we compute the biases in the hydrostatic mass (HE mass) and those in
the gravitational potential, reconstructed from measurements at X-ray and
millimeter wavelengths. In particular, we investigate the effects of the
presence of substructures and of non-thermal pressure support on both the HE
mass and the reconstructed potential. Results. We find that the bias in the
reconstructed potential (6%) is less than that of the HE mass (13%), and that
the scatter in the reconstructed potential decreases by about 35% with respect
to that in the HE mass. Conclusions. This study shows that characterizing
galaxy clusters by their gravitational potential is a promising alternative to
using cluster masses in cluster cosmology.Comment: submitted to the journal A&A, 16 pages, 26 figure
Triaxiality in galaxy clusters: Mass versus Potential reconstructions
Accounting for the triaxial shapes of galaxy clusters will become important
in the context of upcoming cosmological surveys. We show that, compared to the
gas density distribution, the cluster gravitational potential can be better
characterised by a simple 3D model and is more robust against fluctuations.
Perturbations in the gas density distribution can have a substantial influence
on the derived thermodynamic properties, while cluster potentials are smooth
and well-approximated by a spheroidal model. We use a statistical sample of 85
galaxy clusters from a large cosmological hydrodynamical simulation to
investigate cluster shapes as a function of radius. In particular, we examine
the shape of isodensity and isopotential shells and analyze how it is affected
by the choice of component (gas vs. potential), substructure removal (for the
gas density) and the definition of the computation domain (interior vs.
shells). We find that the orientation and axis ratios of gas isodensity
contours are degenerate with the presence of substructures and unstable against
fluctuations. We observe that, as the derived cluster shape depends on the
method used for removing the substructures, thermodynamic properties extracted
from e.g. X-ray emissivity profiles suffer from this additional, often
underestimated bias. In contrast, the shape reconstruction of the potential is
largely unaffected by these factors and converges towards simple geometric
models for both relaxed and dynamically active clusters. The observation that
cluster potentials are better represented by simple geometrical models and
reconstructed with a low level of systematics for both dynamically active and
relaxed clusters suggests that by characterising galaxy clusters by their
potential rather than by their mass, dynamically active and relaxed clusters
could be combined in cosmological studies, improving statistics and lowering
scatter.Comment: Updated with referee's comments, revised version submitted to A&A, 16
pages, 14 figure
Formal Availability Analysis using Theorem Proving
Availability analysis is used to assess the possible failures and their
restoration process for a given system. This analysis involves the calculation
of instantaneous and steady-state availabilities of the individual system
components and the usage of this information along with the commonly used
availability modeling techniques, such as Availability Block Diagrams (ABD) and
Fault Trees (FTs) to determine the system-level availability. Traditionally,
availability analyses are conducted using paper-and-pencil methods and
simulation tools but they cannot ascertain absolute correctness due to their
inaccuracy limitations. As a complementary approach, we propose to use the
higher-order-logic theorem prover HOL4 to conduct the availability analysis of
safety-critical systems. For this purpose, we present a higher-order-logic
formalization of instantaneous and steady-state availability, ABD
configurations and generic unavailability FT gates. For illustration purposes,
these formalizations are utilized to conduct formal availability analysis of a
satellite solar array, which is used as the main source of power for the Dong
Fang Hong-3 (DFH-3) satellite.Comment: 16 pages. arXiv admin note: text overlap with arXiv:1505.0264
Therapeutic recreation as a developing profession in South Africa
South Africa experiences socio-economic challenges with a high prevalence of poverty resulting in disability and non-communicable diseases affecting the health and welfare of communities. Health services are not always accessible or available to citizens, especially those of previously disadvantaged or rural communities. The South African National Plan for Development 2030 aims to address these inequality and health issues. One focus area of this plan is the inclusion of recreation, leisure and sport as an important service sector to improve the health and well-being of all individuals. Therapeutic recreation could play an important role in this regard. In South Africa, therapeutic recreation is in its developmental stages. This paper aims to provide the reader with an overview of therapeutic recreation in South Africa as a developing profession. An overview of the current status of the profession is discussed in terms of standard of practice and as it relates to health professions and recreation service providers, programmes with therapeutic value and training needs. The study concludes that there is still groundwork to be done, calling for interested parties to embark on an aggressive advocacy and strategic planning process to develop therapeutic recreation as a profession in South Africa.Scopu
α-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate
BACKGROUND: A strategy to reduce the secondary effects of anti-cancer agents is to potentiate the therapeutic effect by their
combination. A combination of vitamin K3 (VK3) and ascorbic acid (AA) exhibited an anti-cancer synergistic effect, associated with
extracellular production of H2O2 that promoted cell death.
METHODS: The redox-silent vitamin E analogue a-tocopheryl succinate (a-TOS) was used in combination with VK3 and AA to evaluate their effect on prostate cancer cells.
RESULTS: Prostate cancer cells were sensitive to a-TOS and VK3 treatment, but resistant to AA upto 3.2mM. When combined, a
synergistic effect was found for VK3\u2013AA, whereas a-TOS\u2013VK3 and a-TOS\u2013AA combination showed an antagonist and additive
effect, respectively. However, sub-lethal doses of AA\u2013VK3 combination combined with a sub-toxic dose of a-TOS showed to induce efficient cell death that resembles autoschizis. Associated with this cell demise, lipid peroxidation, DNA damage, cytoskeleton
alteration, lysosomal\u2013mitochondrial perturbation, and release of cytochrome c without caspase activation were observed. Inhibition
of lysosomal proteases did not attenuate cell death induced by the combined agents. Furthermore, cell deaths by apoptosis and
autoschizis were detected.
CONCLUSION: These finding support the emerging idea that synergistic combinations of some agents can overcome toxicity and other side-effects associated with high doses of single drugs creating the opportunity for therapeutically relevant selectivity
Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner
Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes
BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events
Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013
Background: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian metaregression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks
Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.
BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700
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