574 research outputs found
OnabotulinumtoxinA 100U provides significant improvements in overactive bladder symptoms in patients with urinary incontinence regardless of the number of anticholinergic therapies used or reason for inadequate management of overactive bladder
INTRODUCTION: A prespecified pooled analysis of two placebo-controlled, phase 3 trials evaluated whether the number of prior anticholinergics used or reason for their discontinuation affected the treatment response to onabotulinumtoxinA 100U in overactive bladder (OAB) patients with urinary incontinence (UI). METHODS: Patients with symptoms of OAB received intradetrusor injections of onabotulinumtoxinA 100U or placebo, sparing the trigone. Change from baseline at week 12 in UI episodes/day, proportion of patients reporting a positive response (‘greatly improved’ or ‘improved’) on the treatment benefit scale (TBS), micturition and urgency were evaluated by number of prior anticholinergics (1, 2 or ≥ 3) and reason for their discontinuation (insufficient efficacy or side effects). Adverse events (AE) were assessed. RESULTS: Patients had taken an average of 2.4 anticholinergics before study enrolment. OnabotulinumtoxinA reduced UI episodes/day from baseline vs. placebo, regardless of the number of prior anticholinergics (−2.82 vs. −1.52 for one prior anticholinergic; −2.58 vs. −0.58 for two prior anticholinergics; and −2.92 vs. −0.73 for three or more prior anticholinergics; all p < 0.001). The proportion of TBS responders was higher with onabotulinumtoxinA vs. placebo (69.0% vs. 37.2% for one prior anticholinergic; 58.8% vs. 24.8% for two prior anticholinergics and 56.4% vs. 22.5% for three or more prior anticholinergics; all p < 0.001). Similar results were observed regardless of the reason for discontinuation. OnabotulinumtoxinA reduced the episodes of urgency and frequency of micturition vs. placebo in all groups. AEs were well tolerated, with a comparable incidence in all groups. CONCLUSION: In patients with symptoms of OAB who were inadequately managed by one or more anticholinergics, onabotulinumtoxinA 100U provided significant and similar treatment benefit and safety profile regardless of the number of prior anticholinergics used or reason for inadequate management of OAB. ClinicalTrials.gov: NCT00910845, NCT00910520
Communicating Josephson Qubits
We propose a scheme to implement a quantum information transfer protocol with
a superconducting circuit and Josephson charge qubits. The information exchange
is mediated by an L-C resonator used as a data bus. The main decoherence
sources are analyzed in detail.Comment: 4 pages, 2 figure
A biophysical model of prokaryotic diversity in geothermal hot springs
Recent field investigations of photosynthetic bacteria living in geothermal
hot spring environments have revealed surprisingly complex ecosystems, with an
unexpected level of genetic diversity. One case of particular interest involves
the distribution along hot spring thermal gradients of genetically distinct
bacterial strains that differ in their preferred temperatures for reproduction
and photosynthesis. In such systems, a single variable, temperature, defines
the relevant environmental variation. In spite of this, each region along the
thermal gradient exhibits multiple strains of photosynthetic bacteria adapted
to several distinct thermal optima, rather than the expected single thermal
strain adapted to the local environmental temperature. Here we analyze
microbiology data from several ecological studies to show that the thermal
distribution field data exhibit several universal features independent of
location and specific bacterial strain. These include the distribution of
optimal temperatures of different thermal strains and the functional dependence
of the net population density on temperature. Further, we present a simple
population dynamics model of these systems that is highly constrained by
biophysical data and by physical features of the environment. This model can
explain in detail the observed diversity of different strains of the
photosynthetic bacteria. It also reproduces the observed thermal population
distributions, as well as certain features of population dynamics observed in
laboratory studies of the same organisms
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Membrane Hsp70 — a novel target for the isolation of circulating tumor cells after epithelial-to-mesenchymal transition
The presence of circulating tumor cells (CTCs) in the peripheral blood is a pre-requisite for progression, invasion, and metastatic spread of cancer. Consequently, the enumeration and molecular characterization of CTCs from the peripheral blood of patients with solid tumors before, during and after treatment serves as a valuable tool for categorizing disease, evaluating prognosis and for predicting and monitoring therapeutic responsiveness. Many of the techniques for isolating CTCs are based on the expression of epithelial cell surface adhesion molecule (EpCAM, CD326) on tumor cells. However, the transition of adherent epithelial cells to migratory mesenchymal cells (epithelial-to-mesenchymal transition, EMT)—an essential element of the metastatic process—is frequently associated with a loss of expression of epithelial cell markers, including EpCAM. A highly relevant proportion of mesenchymal CTCs cannot therefore be isolated using techniques that are based on the “capture” of cells expressing EpCAM. Herein, we provide evidence that a monoclonal antibody (mAb) directed against a membrane-bound form of Hsp70 (mHsp70)—cmHsp70.1—can be used for the isolation of viable CTCs from peripheral blood of tumor patients of different entities in a more quantitative manner. In contrast to EpCAM, the expression of mHsp70 remains stably upregulated on migratory, mesenchymal CTCs, metastases and cells that have been triggered to undergo EMT. Therefore, we propose that approaches for isolating CTCs based on the capture of cells that express mHsp70 using the cmHsp70.1 mAb are superior to those based on EpCAM expression
Bridging the data gaps in the epidemiology of hepatitis C virus infection in Malaysia using multi-parameter evidence synthesis
BACKGROUND: Collecting adequate information on key epidemiological indicators is a prerequisite to informing a public health response to reduce the impact of hepatitis C virus (HCV) infection in Malaysia. Our goal was to overcome the acute data shortage typical of low/middle income countries using statistical modelling to estimate the national HCV prevalence and the distribution over transmission pathways as of the end of 2009. METHODS: Multi-parameter evidence synthesis methods were applied to combine all available relevant data sources - both direct and indirect - that inform the epidemiological parameters of interest. RESULTS: An estimated 454,000 (95% credible interval [CrI]: 392,000 to 535,000) HCV antibody-positive individuals were living in Malaysia in 2009; this represents 2.5% (95% CrI: 2.2-3.0%) of the population aged 15-64 years. Among males of Malay ethnicity, for 77% (95% CrI: 69-85%) the route of probable transmission was active or a previous history of injecting drugs. The corresponding proportions were smaller for male Chinese and Indian/other ethnic groups (40% and 71%, respectively). The estimated prevalence in females of all ethnicities was 1% (95% CrI: 0.6 to 1.4%); 92% (95% CrI: 88 to 95%) of infections were attributable to non-drug injecting routes of transmission. CONCLUSIONS: The prevalent number of persons living with HCV infection in Malaysia is estimated to be very high. Low/middle income countries often lack a comprehensive evidence base; however, evidence synthesis methods can assist in filling the data gaps required for the development of effective policy to address the future public health and economic burden due to HCV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0564-6) contains supplementary material, which is available to authorized users
An early European experience with transapical off-pump mitral valve repair with NeoChord implantation
OBJECTIVES: Transapical off-pump NeoChord repair is a novel minimally invasive surgical procedure to treat degenerative mitral valve regurgitation. The aim was to evaluate 1-year clinical results of the NeoChord procedure in a consecutive cohort of patients. METHODS: Between February 2013 and July 2016, 213 patients were enrolled in the NeoChord Independent International Registry. All patients presented severe mitral regurgitation due to flail/prolapse of 1 or both leaflets, and they all completed postoperative echocardiographic assessment up to 1 year. We identified the primary end point as composed of procedural success, freedom from mortality, stroke, reintervention, recurrence of severe mitral regurgitation, rehospitalization and decrease of at least 1 New York Heart Association functional class at 1-year follow-up. We also compared outcomes according to the anatomical classification (Type A: isolated central posterior leaflet disease; Type B: posterior multisegment disease; Type C: anterior, bileaflet, paracommissural disease with/without leaflet/annular calcifications). RESULTS: The median age was 68 years (interquartile range 56-77), and the median EuroSCORE II was 1.05% (interquartile range 0.67-1.76). The number of Type A, B and C patients was 82 (38.5%), 98 (46%) and 33 (15.5%), respectively. Procedural success was achieved in 206 (96.7%) patients. At 1-year follow-up, overall survival was 98 ± 1%. Composite end point was achieved in 84 ± 2.5% for the overall population and 94 ± 2.6%, 82.6 ± 3.8% and 63.6 ± 8.4% in Type A, Type B and Type C patients, respectively (P < 0.0001). CONCLUSIONS: These results demonstrate that the NeoChord procedure is safe, effective and reproducible. Clinical and echocardiographic efficacy is maintained up to 1 year with significant differences among the anatomical groups. Specific anatomical selection criteria are necessary to achieve stable results
Versagenssimulation dynamisch belasteter Proben mit unterschiedlichen Mehrachsigkeitszuständen unter Verwendung des Johnson-Cook-Versagensmodells für eine Nickelbasislegierung
Das Versagensverhalten verschiedener prismatischer Scherproben wurde in einer Split-Hopkinson-Pressure-Bar-Anlage und das verschiedener gekerbter Rundzugproben in einer Schnellzerreißmaschine bei hohen Dehnraten untersucht. In Finite-Elemente-Simulationen mit ausschließlich einem viskoplastischen Deformationsmodell (Johnson-Cook), das thermische Entfestigung berücksichtigt, werden die experimentellen Kraft-Zeit-Verläufe weder bezüglich des Zeitpunktes des Einsetzens des Versagens noch bezüglich des dann auftretenden starken Kraftabfalls richtig wiedergegeben. Erst bei zusätzlicher Verwendung eines Schädigungs- bzw. Versagensmodells ist eine zufriedenstellende Übereinstimmung von Experiment und Simulation zu erzielen. Bei den vorgestellten Untersuchungen wurde das Johnson-Cook -Versagensmodell verwendet, das auch den Einfluss der Mehrachsigkeit berücksichtigt. Das Materialverhalten kann in Versuchen, die einen breiten Bereich von Mehrachsigkeiten aufweisen, mit nur einem Satz von Materialparametern simuliert werden
Three-dimensional effects on extended states in disordered models of polymers
We study electronic transport properties of disordered polymers in the
presence of both uncorrelated and short-range correlated impurities. In our
procedure, the actual physical potential acting upon the electrons is replaced
by a set of nonlocal separable potentials, leading to a Schr\"odinger equation
that is exactly solvable in the momentum representation. We then show that the
reflection coefficient of a pair of impurities placed at neighboring sites
(dimer defect) vanishes for a particular resonant energy. When there is a
finite number of such defects randomly distributed over the whole lattice, we
find that the transmission coefficient is almost unity for states close to the
resonant energy, and that those states present a very large localization
length. Multifractal analysis techniques applied to very long systems
demonstrate that these states are truly extended in the thermodynamic limit.
These results reinforce the possibility to verify experimentally theoretical
predictions about absence of localization in quasi-one-dimensional disordered
systems.Comment: 16 pages, REVTeX 3.0, 5 figures on request from FDA
([email protected]). Submitted to Phys. Rev. B. MA/UC3M/09/9
Immunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B
Background: We have previously reported that human recombinant granzyme B (grB) mediates apoptosis in membrane heat shock protein 70 (Hsp70)-positive tumor cells in a perforin-independent manner
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