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

Fluid flow stimulates chemoautotrophy in hydrothermally influenced coastal sediments

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Sievert, S. M., Buehring, S., Gulmann, L. K., Hinrichs, K.-U., Ristova, P. P., & Gomez-Saez, G. Fluid flow stimulates chemoautotrophy in hydrothermally influenced coastal sediments. Communications Earth & Environment, 3(1), (2022): 96, https://doi.org/10.1038/s43247-022-00426-5.Hydrothermalism in coastal sediments strongly impacts biogeochemical processes and supports chemoautotrophy. Yet, the effect of fluid flow on microbial community composition and rates of chemoautotrophic production is unknown because rate measurements under natural conditions are difficult, impeding an assessment of the importance of these systems. Here, in situ incubations controlling fluid flow along a transect of three geochemically distinct locations at a shallow-water hydrothermal system off Milos (Greece) show that Campylobacteria dominated chemoautotrophy in the presence of fluid flow. Based on injected 13C-labelled dissolved inorganic carbon and its incorporation into fatty acids, we constrained carbon fixation to be as high as 12 µmol C cm−3 d−1, corresponding to areal rates up to 10-times higher than previously reported for coastal sediments, and showed the importance of fluid flow for supplying the necessary substrates to support chemoautotrophy. Without flow, rates were substantially lower and microbial community composition markedly shifted. Our results highlight the importance of fluid flow in shaping the composition and activity of microbial communities of shallow-water hydrothermal vents, identifying them as hotspots of microbial productivity.Open Access funding enabled and organized by Projekt DEAL

Single cell genomics-based analysis of gene content and expression of prophages in a diffuse-flow deep-sea hydrothermal system

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Labonte, J. M., Pachiadaki, M., Fergusson, E., McNichol, J., Grosche, A., Gulmann, L. K., Vetriani, C., Sievert, S. M., & Stepanauskas, R. Single cell genomics-based analysis of gene content and expression of prophages in a diffuse-flow deep-sea hydrothermal system. Frontiers in Microbiology, 10, (2019): 1262, doi:10.3389/fmicb.2019.01262.Phage–host interactions likely play a major role in the composition and functioning of many microbiomes, yet remain poorly understood. Here, we employed single cell genomics to investigate phage–host interactions in a diffuse-flow, low-temperature hydrothermal vent that may be reflective of a broadly distributed biosphere in the subseafloor. We identified putative prophages in 13 of 126 sequenced single amplified genomes (SAGs), with no evidence for lytic infections, which is in stark contrast to findings in the surface ocean. Most were distantly related to known prophages, while their hosts included bacterial phyla Campylobacterota, Bacteroidetes, Chlorobi, Proteobacteria, Lentisphaerae, Spirochaetes, and Thermotogae. Our results suggest the predominance of lysogeny over lytic interaction in diffuse-flow, deep-sea hydrothermal vents, despite the high activity of the dominant Campylobacteria that would favor lytic infections. We show that some of the identified lysogens have co-evolved with their host over geological time scales and that their genes are transcribed in the environment. Functional annotations of lysogeny-related genes suggest involvement in horizontal gene transfer enabling host’s protection against toxic metals and antibacterial compounds.This work was supported by the U.S. National Science Foundation’s Dimensions of Biodiversity Program [OCE-1136488 (to RS), OCE-1136727 (to SMS) and OCE-1136451 (to CV)], as well as DEB-1441717 and OCE-1335810 (to RS), and the DOE JGI CSP project 1477

The accident insurance as a promising direction for insurance in Russia

Статья посвящена анализу состояния рынка услуг страхования от несчастных случаев. Актуальность исследования определяется тем, что страхование является неотъемлемым атрибутом цивилизованного общества, позволяющим сохранить обеспеченность доходами при неблагоприятных ситуациях. По статистике в России уровень травматизма и непредвиденных обстоятельств весьма велик. Люди традиционно уделяют мало внимания формированию резервов на случай временной или постоянной нетрудоспособности. Цель работы: рассмотреть систему страхования от несчастных случаев. Методы исследования: метод сопоставления, необходимый для выявления главных тенденций на рынке страховых услуг; аналитический метод, позволяющий понять, какие проблемы характерны для этого вида страхования; статистический метод, выявляющий масштабы страхования от несчастных случаев. Результаты: раскрывается сущность и виды страхования от несчастных случаев.The article is devoted to analysis of service market of accident insurance. The relevant of the study is determined by the fact that insurance is an integral attribute of a civilized society that allows you to save security income in adverse situations. According to statistics, in Russia the level of injury and unforeseen circumstances is very great. People traditionally pay little attention to formation of reserves in case of temporary or permanent incapacity for work. The main aim of the study is to consider the system of the accident insurance. Methods: the matching method required to identify the main trends in the insurance market; the analytical technique which allows understanding the typical problems for this type of insurance; the statistical method allows us to identify the extent of accident insurance. Results. The paper reveals the essence and types of accident insurance and considers the model events when the insurance company indemnifies for the damage. The causes of the demand for this type of insurance in Russia are identified. Based on the statistical data the author has determined the proportion of the accident insured people

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

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

Stereospecific inhibition of monoamine uptake transporters by meta-hydroxyephedrine isomers

Meta-hydroxyephedrine (HED) comprises four stereoisomers consisting of two enantiomeric pairs related to ephedrine and pseudoephedrine. HED is transported into adrenergic neurons and radiolabeled HED has been employed in positron emission tomography (PET) to image adrenergic neurons in vivo. To extend structure-activity analyses of binding sites within monoamine transporters and to determine which stereoisomer displayed the best selectivity for PET imaging applications, we tested the HED compounds for their abilities to inhibit [ 3 H]neurotransmitter uptake into platelets, transfected cells, and chromaffin vesicles. We hypothesized that the HED compounds would be most potent at the norepinephrine transporter (NET) compared to the serotonin or dopamine transporters and that the 1R diastereomers would be more effective than 1S diastereomers. Supporting the hypotheses, all stereoisomers were most potent at the NET and the 1R,2S stereoisomer was the most potent inhibitor overall. However, the 1S,2R isomer may be preferred for PET applications because of better selectivity among the transporters and reduced neuronal recycling.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42456/1/702-109-10-1229_21091229.pd

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

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