3,104 research outputs found
Transcatheter Aortic Valve Implantation in Dialysis Patients
Background/Aims: Transcatheter aortic valve implantation (TAVI) has emerged as a new therapeutic option for high-risk patients. However, dialysis patients were excluded from all previous studies. The aim of this study is to compare the outcomes of TAVI for dialysis patients with those for patients with chronic kidney disease (CKD) stages 3 and 4 and to compare TAVI with open surgery in dialysis patients. Methods: Part I: comparison of 10 patients on chronic hemodialysis with 116 patients with non-dialysis-dependent CKD undergoing TAVI. Part II: comparison of transcatheter (n = 15) with open surgical (n = 24) aortic valve replacement in dialysis patients. Results: Part I: dialysis patients were significantly younger (72.3 vs. 82.0 years; p < 0.01). Hospital stay was significantly longer in dialysis patients (21.8 vs. 12.1 days; p = 0.01). Overall 30-day mortality was 3.17%, with no deaths among dialysis patients. Six-month survival rates were similar (log-rank p = 0.935). Part II: patient age was comparable (66.5 vs. 69.5 years; p = 0.42). Patients in the surgical group tended to stay longer in hospital than TAVI patients (29.5 vs. 22.5 days; p = 0.35). Conclusion: TAVI is a safe procedure in patients on chronic hemodialysis. Until new data become available, we find no compelling reason to refuse these patients TAVI. Copyright (C) 2012 S. Karger AG, Base
QCD with Chemical Potential in a Small Hyperspherical Box
To leading order in perturbation theory, we solve QCD, defined on a small
three sphere in the large N and Nf limit, at finite chemical potential and map
out the phase diagram in the (mu,T) plane. The action of QCD is complex in the
presence of a non-zero quark chemical potential which results in the sign
problem for lattice simulations. In the large N theory, which at low
temperatures becomes a conventional unitary matrix model with a complex action,
we find that the dominant contribution to the functional integral comes from
complexified gauge field configurations. For this reason the eigenvalues of the
Polyakov line lie off the unit circle on a contour in the complex plane. We
find at low temperatures that as mu passes one of the quark energy levels there
is a third-order Gross-Witten transition from a confined to a deconfined phase
and back again giving rise to a rich phase structure. We compare a range of
physical observables in the large N theory to those calculated numerically in
the theory with N=3. In the latter case there are no genuine phase transitions
in a finite volume but nevertheless the observables are remarkably similar to
the large N theory.Comment: 44 pages, 18 figures, jhep3 format. Small corrections and
clarifications added in v3. Conclusions cleaned up. Published versio
Gravitational detection of a low-mass dark satellite at cosmological distance
The mass-function of dwarf satellite galaxies that are observed around Local
Group galaxies substantially differs from simulations based on cold dark
matter: the simulations predict many more dwarf galaxies than are seen. The
Local Group, however, may be anomalous in this regard. A massive dark satellite
in an early-type lens galaxy at z = 0.222 was recently found using a new method
based on gravitational lensing, suggesting that the mass fraction contained in
substructure could be higher than is predicted from simulations. The lack of
very low mass detections, however, prohibited any constraint on their mass
function. Here we report the presence of a 1.9 +/- 0.1 x 10^8 M_sun dark
satellite in the Einstein-ring system JVAS B1938+666 at z = 0.881, where M_sun
denotes solar mass. This satellite galaxy has a mass similar to the Sagittarius
galaxy, which is a satellite of the Milky Way. We determine the logarithmic
slope of the mass function for substructure beyond the local Universe to be
alpha = 1.1^+0.6_-0.4, with an average mass-fraction of f = 3.3^+3.6_-1.8 %, by
combining data on both of these recently discovered galaxies. Our results are
consistent with the predictions from cold dark matter simulations at the 95 per
cent confidence level, and therefore agree with the view that galaxies formed
hierarchically in a Universe composed of cold dark matter.Comment: 25 pages, 7 figures, accepted for publication in Nature (19 January
2012
Extinction times in the subcritical stochastic SIS logistic epidemic
Many real epidemics of an infectious disease are not straightforwardly super-
or sub-critical, and the understanding of epidemic models that exhibit such
complexity has been identified as a priority for theoretical work. We provide
insights into the near-critical regime by considering the stochastic SIS
logistic epidemic, a well-known birth-and-death chain used to model the spread
of an epidemic within a population of a given size . We study the behaviour
of the process as the population size tends to infinity. Our results cover
the entire subcritical regime, including the "barely subcritical" regime, where
the recovery rate exceeds the infection rate by an amount that tends to 0 as but more slowly than . We derive precise asymptotics for
the distribution of the extinction time and the total number of cases
throughout the subcritical regime, give a detailed description of the course of
the epidemic, and compare to numerical results for a range of parameter values.
We hypothesise that features of the course of the epidemic will be seen in a
wide class of other epidemic models, and we use real data to provide some
tentative and preliminary support for this theory.Comment: Revised; 34 pages; 6 figure
Patient-centric trials for therapeutic development in precision oncology
An enhanced understanding of the molecular pathology of disease gained from genomic studies is facilitating the development of treatments that target discrete molecular subclasses of tumours. Considerable associated challenges include how to advance and implement targeted drug-development strategies. Precision medicine centres on delivering the most appropriate therapy to a patient on the basis of clinical and molecular features of their disease. The development of therapeutic agents that target molecular mechanisms is driving innovation in clinical-trial strategies. Although progress has been made, modifications to existing core paradigms in oncology drug development will be required to realize fully the promise of precision medicine
A restatement of the natural science evidence concerning catchment-based "natural” flood management in the United Kingdom
Flooding is a very costly natural hazard in Great Britain and is expected to increase further
under future climate change scenarios. Flood defences are commonly deployed to protect
communities and property from flooding, but in recent years flood management policy has
looked towards solutions that seek to mitigate flood risk at flood-prone sites through targeted
interventions throughout the catchment, sometimes using techniques which involve working
with natural processes. This paper describes a project to provide a succinct summary of the
natural science evidence base concerning the effectiveness of catchment-based “natural” flood
management in the United Kingdom. The evidence summary is designed to be read by an
informed but not technically-specialist audience. Each evidence statement is placed into one
of four categories describing the nature of the underlying information. The evidence summary
forms the appendix to this paper and an annotated bibliography is provided in the electronic
supplementary material
Herd-level animal management factors associated with the occurrence of bovine neonatal pancytopenia in calves in a multicountry study
Since 2007, mortality associated with a previously unreported haemorrhagic disease has been observed in young calves in several European countries. The syndrome, which has been named ‘bovine neonatal pancytopenia’ (BNP), is characterised by thrombocytopenia, leukocytopenia and a panmyelophthisis. A herd-level case-control study was conducted in four BNP affected countries (Belgium, France, Germany and the Netherlands) to identify herd management risk factors for BNP occurrence. Data were collected using structured face-to-face and telephone interviews of farm managers and their local veterinarians. In total, 363 case farms and 887 control farms were included in a matched multivariable conditional logistic regression analysis. Case-control status was strongly associated with the odds of herd level use of the vaccine PregSure® BVD (PregSure, Pfizer Animal Health) (matched adjusted odds ratio (OR) 107.2; 95% CI: 41.0–280.1). This was also the case for the practices of feeding calves colostrum from the calf’s own dam (OR 2.0; 95% CI: 1.1–3.4) or feeding pooled colostrum (OR 4.1; 95% CI: 1.9–8.8). Given that the study had relatively high statistical power and represented a variety of cattle production and husbandry systems, it can be concluded with some confidence that no other herd level management factors are competent causes for a sufficient cause of BNP occurrence on herd level. It is suggested that genetic characteristics of the dams and BNP calves should be the focus of further investigations aimed at identifying the currently missing component causes that together with PregSure vaccination and colostrum feeding represent a sufficient cause for occurrence of BNP in calves
Entanglement entropy of Wilson surfaces from bubbling geometries in M-theory
We consider solutions of eleven-dimensional supergravity constructed in [1,2]
that are half-BPS, locally asymptotic to and are the
holographic dual of heavy Wilson surfaces in the six-dimensional
theory. Using these bubbling solutions we calculate the holographic
entanglement entropy for a spherical entangling surface in the presence of a
planar Wilson surface. In addition, we calculate the holographic stress tensor
and, by evaluating the on-shell supergravity action, the expectation value of
the Wilson surface operator.Comment: 42 pages, 4 figures, v2: minor modification
Role of CD14+ monocyte-derived oxidised mitochondrial DNA in the inflammatory interferon type 1 signature in juvenile dermatomyositis
OBJECTIVES: To define the host mechanisms contributing to the pathological interferon (IFN) type 1 signature in Juvenile dermatomyositis (JDM). METHODS: RNA-sequencing was performed on CD4+, CD8+, CD14+ and CD19+ cells sorted from pretreatment and on-treatment JDM (pretreatment n=10, on-treatment n=11) and age/sex-matched child healthy-control (CHC n=4) peripheral blood mononuclear cell (PBMC). Mitochondrial morphology and superoxide were assessed by fluorescence microscopy, cellular metabolism by 13C glucose uptake assays, and oxidised mitochondrial DNA (oxmtDNA) content by dot-blot. Healthy-control PBMC and JDM pretreatment PBMC were cultured with IFN-α, oxmtDNA, cGAS-inhibitor, TLR-9 antagonist and/or n-acetyl cysteine (NAC). IFN-stimulated gene (ISGs) expression was measured by qPCR. Total numbers of patient and controls for functional experiments, JDM n=82, total CHC n=35. RESULTS: Dysregulated mitochondrial-associated gene expression correlated with increased ISG expression in JDM CD14+ monocytes. Altered mitochondrial-associated gene expression was paralleled by altered mitochondrial biology, including 'megamitochondria', cellular metabolism and a decrease in gene expression of superoxide dismutase (SOD)1. This was associated with enhanced production of oxidised mitochondrial (oxmt)DNA. OxmtDNA induced ISG expression in healthy PBMC, which was blocked by targeting oxidative stress and intracellular nucleic acid sensing pathways. Complementary experiments showed that, under in vitro experimental conditions, targeting these pathways via the antioxidant drug NAC, TLR9 antagonist and to a lesser extent cGAS-inhibitor, suppressed ISG expression in pretreatment JDM PBMC. CONCLUSIONS: These results describe a novel pathway where altered mitochondrial biology in JDM CD14+ monocytes lead to oxmtDNA production and stimulates ISG expression. Targeting this pathway has therapeutical potential in JDM and other IFN type 1-driven autoimmune diseases
Individual rules for trail pattern formation in Argentine ants (Linepithema humile)
We studied the formation of trail patterns by Argentine ants exploring an
empty arena. Using a novel imaging and analysis technique we estimated
pheromone concentrations at all spatial positions in the experimental arena and
at different times. Then we derived the response function of individual ants to
pheromone concentrations by looking at correlations between concentrations and
changes in speed or direction of the ants. Ants were found to turn in response
to local pheromone concentrations, while their speed was largely unaffected by
these concentrations. Ants did not integrate pheromone concentrations over
time, with the concentration of pheromone in a 1 cm radius in front of the ant
determining the turning angle. The response to pheromone was found to follow a
Weber's Law, such that the difference between quantities of pheromone on the
two sides of the ant divided by their sum determines the magnitude of the
turning angle. This proportional response is in apparent contradiction with the
well-established non-linear choice function used in the literature to model the
results of binary bridge experiments in ant colonies (Deneubourg et al. 1990).
However, agent based simulations implementing the Weber's Law response function
led to the formation of trails and reproduced results reported in the
literature. We show analytically that a sigmoidal response, analogous to that
in the classical Deneubourg model for collective decision making, can be
derived from the individual Weber-type response to pheromone concentrations
that we have established in our experiments when directional noise around the
preferred direction of movement of the ants is assumed.Comment: final version, 9 figures, submitted to Plos Computational Biology
(accepted
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