Objective
To characterise vaginal bacterial composition in early pregnancy and investigate its relationship with first and second trimester miscarriages.
Design
Nested case–control study.
Setting
...Queen Charlotte’s and Chelsea Hospital, Imperial College Healthcare NHS Trust, London.
Population
161 pregnancies: 64 resulting in first trimester miscarriage, 14 in second trimester miscarriage and 83 term pregnancies.
Methods
Prospective profiling and comparison of vaginal bacteria composition using 16S rRNA gene‐based metataxonomics from 5 weeks’ gestation in pregnancies ending in miscarriage or uncomplicated term deliveries matched for age, gestation and body mass index.
Main outcome measures
Relative vaginal bacteria abundance, diversity and richness. Pregnancy outcomes defined as first or second trimester miscarriage, or uncomplicated term delivery.
Results
First trimester miscarriage associated with reduced prevalence of Lactobacillus spp.‐dominated vaginal microbiota classified using hierarchical clustering analysis (65.6 versus 87.7%; P = 0.005), higher alpha diversity (mean Inverse Simpson Index 2.5 95% confidence interval 1.8–3.0 versus 1.5 1.3–1.7, P = 0.003) and higher richness 25.1 (18.5–31.7) versus 16.7 (13.4–20), P = 0.017), compared with viable pregnancies. This was independent of vaginal bleeding and observable before first trimester miscarriage diagnosis (P = 0.015). Incomplete/complete miscarriage associated with higher proportions of Lactobacillus spp.‐depleted communities compared with missed miscarriage. Early pregnancy vaginal bacterial stability was similar between miscarriage and term pregnancies.
Conclusions
These findings associate the bacterial component of vaginal microbiota with first trimester miscarriage and indicate suboptimal community composition is established in early pregnancy. While further studies are required to elucidate the mechanism, vaginal bacterial composition may represent a modifiable risk factor for first trimester miscarriage.
Tweetable
Vaginal bacterial composition in first trimester miscarriage is associated with reduced Lactobacillus spp. abundance and is independent of vaginal bleeding.
Tweetable
Vaginal bacterial composition in first trimester miscarriage is associated with reduced Lactobacillus spp. abundance and is independent of vaginal bleeding.
is an encapsulated yeast responsible for approximately a quarter of a million deaths worldwide annually despite therapy, and upwards of 11% of HIV/AIDS-related deaths, rivaling the impact of ...tuberculosis and malaria. However, the most effective antifungal agent, amphotericin B, requires intravenous delivery and has significant renal and hematopoietic toxicity, making it difficult to utilize, especially in resource-limited settings. The present studies describe a new nanoparticle crystal encapsulated formulation of amphotericin B known as encochleated amphotericin B (CAmB) that seeks to provide an oral formulation that is low in toxicity and cost. Using a 3-day delayed model of murine cryptococcal meningoencephalitis and a large inoculum of a highly virulent strain of serotype A
, CAmB, in combination with flucytosine, was found to have efficacy equivalent to parental amphotericin B deoxycholate with flucytosine and superior to oral fluconazole without untoward toxicity. Transport of fluorescent CAmB particles to brain as well as significant brain levels of amphotericin drug was demonstrated in treated mice, and immunological profiles were similar to those of mice treated with conventional amphotericin B. Additional toxicity studies using a standardized rat model showed negligible toxicity after a 28-day treatment schedule. These studies thus offer the potential for an efficacious oral formulation of a known fungicidal drug against intrathecal cryptococcal disease.
is a significant global fungal pathogen that kills an estimated quarter of a million HIV-infected individuals yearly and has poor outcomes despite therapy. The most effective therapy, amphotericin B, is highly effective in killing the fungus but is available only in highly toxic, intravenous formulations that are unavailable in most of the developing world, where cryptococcal disease in most prevalent. For example, in Ethiopia, reliance on the orally available antifungal fluconazole results in high mortality, even when initiated as preemptive therapy at the time of HIV diagnosis. Thus, alternative agents could result in significant saving of lives. Toward this end, the present work describes the development of a new formulation of amphotericin B (CAmB) that encapsulates the drug as a crystal lipid nanoparticle that facilitates oral absorption and prevents toxicity. Successful oral absorption of the drug was demonstrated in a mouse model that, in combination with the antifungal flucytosine, provided efficacy equal to a parental preparation of amphotericin B plus flucytosine. These studies demonstrate the potential for CAmB in combination with flucytosine to provide an effective oral formulation of a well-known, potent fungicidal drug combination.
An ultra-low background PMT for liquid xenon detectors Akerib, D.S.; Bai, X.; Bernard, E. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
03/2013, Letnik:
703
Journal Article
Recenzirano
Odprti dostop
Results are presented from radioactivity screening of two models of photomultiplier tubes designed for use in current and future liquid xenon experiments. The Hamamatsu 5.6cm diameter R8778 PMT, used ...in the LUX dark matter experiment, has yielded a positive detection of four common radioactive isotopes: 238U, 232Th, 40K, and 60Co. Screening of LUX materials has rendered backgrounds from other detector materials subdominant to the R8778 contribution. A prototype Hamamatsu 7.6cm diameter R11410 MOD PMT has also been screened, with benchmark isotope counts measured at <0.4238U/<0.3232Th/<8.340K/2.0±0.2 60Co mBq/PMT. This represents a large reduction, equal to a change of ×124238U/×19232Th/×1840K per PMT, between R8778 and R11410 MOD, concurrent with a doubling of the photocathode surface area (4.5–6.4cm diameter). 60Co measurements are comparable between the PMTs, but can be significantly reduced in future R11410 MOD units through further material selection. Assuming PMT activity equal to the measured 90% upper limits, Monte Carlo estimates indicate that replacement of R8778 PMTs with R11410 MOD PMTs will change LUX PMT electron recoil background contributions by a factor of ×125 after further material selection for 60Co reduction, and nuclear recoil backgrounds by a factor of ×136. The strong reduction in backgrounds below the measured R8778 levels makes the R11410 MOD a very competitive technology for use in large-scale liquid xenon detectors.
LUX is a two-phase (liquid/gas) xenon time projection chamber designed to detect nuclear recoils from interactions with dark matter particles. Signals from the LUX detector are processed by ...custom-built analog electronics which provide properly shaped signals for the trigger and data acquisition (DAQ) systems. The DAQ is composed of commercial digitizers with firmware customized for the LUX experiment. Data acquisition systems in rare-event searches must accommodate high rate and large dynamic range during precision calibrations involving radioactive sources, while also delivering low threshold for maximum sensitivity. The LUX DAQ meets these challenges using real-time baseline suppression that allows for a maximum event acquisition rate in excess of 1.5kHz with virtually no deadtime. This paper describes the LUX DAQ and the novel acquisition techniques employed in the LUX experiment.
Models that quantify the effects of cropping systems on weed dynamics are useful tools for testing innovative cropping systems. In these models, seed mortality in the soil is a key parameter to ...account for the cumulated effect of cropping systems over time via the soil seed-bank. Since seed mortality is difficult to measure, our objective was to develop a method to estimate it from easily accessible information. Seeds of 13 weed species were buried 30 cm deep in fields and were recovered regularly for 2 years to measure their viability. Seed mass, dimensions, shape, and protein and lipid contents as well as coat thickness were measured. To estimate seed mortality of species not included in the study, we searched for relationships between mortality rates and seed traits. Seed viability mainly decreased during the second year of burial, with mortality rates ranging from 0.01 to 0.63 seeds·seeds− 1·year− 1, depending on the species. Seed mortality decreased with increasing seed coat thickness. No correlation was found with other measured traits or with seed persistence data in the literature. These results were confirmed when the effects of phylogenetic relatedness with phylogenetically independent contrasts were included. The thickness of the seed coat, which varied between 17 and 231 μm over the range of species studied, can protect the seed from external attacks in the soil and slow down seed decay. This trait can be easily measured via X-ray images and could be used to estimate the seed mortality rate for a wider range of species.
From May to October 2006, six severe Pseudomonas aeruginosa infections were diagnosed in patients undergoing SCT in the SCT unit of the Careggi hospital (Florence, Italy). Four of the infected ...patients were treated consecutively in the same room (room N). On the hypothesis of a possible environmental source of infection, samples were collected from different sites that had potential for cross-contamination throughout the SCT unit, including the electrolytic chloroxidant disinfectant used for hand washing (Irgasan) and the disinfectant used for facilities cleaning. Four of the environmental samples were positive for P. aeruginosa: three Irgansan soap samples and a tap swab sample from the staff cleaning and dressing room. The AFLP (amplified fragment length polymorphism) typing method employed to evaluate strain clonality showed that the isolates from the patients who had shared the same room and an isolate from Irgasan soap had a significant molecular similarity (dice index higher than 0.93). After adequate control measures, no subsequent environmental sample proved positive for P. aeruginosa. These data strongly support the hypothesis of the clonal origin of the infective strains and suggest an environmental source of infection. The AFLP method was fast enough to allow a 'real-time' monitoring of the outbreak, permitting additional preventive measures.
The Large Underground Xenon (LUX) experiment is a dual-phase xenon time-projection chamber operating at the Sanford Underground Research Facility (Lead, South Dakota). The LUX cryostat was filled for ...the first time in the underground laboratory in February 2013. We report results of the first WIMP search data set, taken during the period from April to August 2013, presenting the analysis of 85.3 live days of data with a fiducial volume of 118 kg. A profile-likelihood analysis technique shows our data to be consistent with the background-only hypothesis, allowing 90% confidence limits to be set on spin-independent WIMP-nucleon elastic scattering with a minimum upper limit on the cross section of 7.6 × 10(-46) cm(2) at a WIMP mass of 33 GeV/c(2). We find that the LUX data are in disagreement with low-mass WIMP signal interpretations of the results from several recent direct detection experiments.
Introduction
Catheter-related bloodstream infections very often involve the premature removal of long-term intravascular devices (LTID). The antibiotic lock therapy (ALT) represents a conservative ...approach to the treatment of uncomplicated infections of tunneled LTID when catheter removal is not a feasible option.
Case report
We present here the first reported case of tunneled LTID bloodstream infection due to a multidrug resistant
Lactobacillus rhamnosus
. The patient, who had large granular lymphocytic leukemia, was successfully treated with systemic tigecycline therapy and lock therapy.
Conclusion
Our results confirm ALT as a valid catheter-salvage strategy for the treatment of CRBSIs in clinically stable patients when catheter removal is not a feasible option, tigecycline appear to be a good option.
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