211 research outputs found

    Surface air temperature fluctuations and lapse rates on Olivares Gamma Glacier, Rio Olivares basin, central Chile, from a novel meteorological sensor network

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    Empirically based studies of glacier meteorology, especially for the Southern Hemisphere, are relatively sparse in the literature. Here, we use an innovative network of highly-portable, low-cost thermometers to report on high-frequency (1-min time resolution) surface air temperature fluctuations and lapse rates (LR) in a ~800-m elevational range (from 3,675 to 4,492 m a.s.l.) across the glacier Olivares Gamma in the central Andes, Chile. Temperatures were measured during an intense field campaign in late Southern summer, 19–27 March 2015, under varying weather conditions. We found a complex dependence of high-frequency LR on time of day, topography and wider meteorological conditions, with hourly temperature variations during this week that were probably mainly associated with short- and long-wave radiation changes and not with wind speed/direction changes. Using various pairs of sites within our station network, we also analyze spatial variations in LR. Uniquely in this study, we compare temperatures measured at heights of 1-m and 2-m above the glacier surface for the network of five sites, and found that temperatures at these two heights occasionally differed by more than ±4°C during the early afternoons, although the mean temperature difference is much smaller (~0.3°C). An implication of our results is that daily, hourly, or even monthly-averaged LR may be insufficient for feeding into accurate melt models of glacier change, with the adoption of sub-hourly (ideally 1–10-min) resolution LR likely to prove fruitful in developing new innovative high-time-resolution melt modelling. Our results are useful potentially as input LR for local glacier melt models, and for improving the understanding of lapse-rate fluctuations and glacier response to climate change

    Effect of ospemifene on moderate or severe symptoms of vulvar and vaginal atrophy.

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    Objectives To determine whether assessment of all moderate-to-severe symptoms at baseline gives a more accurate evaluation of the treatment effect of ospemifene in vulvovaginal atrophy (VVA) than the most bothersome symptom (MBS) approach. Methods Data were pooled from two pivotal phase-III clinical trials evaluating the efficacy and safety of oral ospemifene 60 mg/day for the treatment of symptoms of VVA (n = 1463 subjects). Symptoms of vaginal dryness, dyspareunia, and vaginal and/or vulvar irritation/itching reported as moderate or severe at baseline were evaluated. Clinically relevant differences between ospemifene and placebo were analyzed using a four-point severity scoring system and presented as improvement, substantial improvement, or relief. Results Subjects in these studies reported statistically significant improvement, substantial improvement, and relief for vaginal dryness (p \u3c 0.00001), dyspareunia (p \u3c 0.001) and statistically significant improvement and relief for vaginal and/or vulvar irritation/itching (p \u3c 0.01) from baseline to week 12 with ospemifene compared with placebo. A similar trend was observed for women who reported substantial improvement of vaginal and/or vulvar irritation/itching. Conclusions For drug registration purposes, the use of the MBS model is appealing because of its simplicity and ease of scientific validation. However, the MBS model may underestimate the total magnitude of the clinical benefit of ospemifene treatment for symptomatic women suffering from VVA

    Inhibiting the Thermal Gelation of Copolymer Stabilized Nonaqueous Dispersions and the Synthesis of Full Color PMMA Particles

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    Polymeric particle dispersions have numerous potential applications; currently one of the most relevant is their use as inks in electrophoretic displays. These colloidal particles are synthesized from the appropriate monomer using nonaqueous dispersion (NAD) polymerization in a nonpolar solvent, which requires a stabilizer to control particle size and morphology. We have previously reported the facile synthesis of poly(methyl methacrylate)-block-poly(octadecyl acrylate) (PMMA-b-PODA) by atom transfer radical polymerization (ATRP), and its use in the NAD polymerization of MMA in hexane/dodecane solvent mixtures. Here we report the synthesis of monodisperse PMMA particles in dodecane following a standard “industrial” procedure using these PMMA-b-PODA stabilizers. However, it was observed that the particle suspensions solidified when they were left at temperatures below ?18 °C yet redispersed upon being heated. Differential scanning calorimetry, dynamic light scattering, and rheological studies demonstrated that this thermoresponsive behavior was due to a liquid–gel transition occurring at 17.5 °C as a consequence of the upper critical solution temperature of PODA in dodecane being traversed. Consequently, new copolymers were synthesized by ATRP with an ethylhexyl acrylate (EHA) co-monomer incorporated into the lyophilic (dodecane compatible) block. Dispersions stabilized by these PMMA-b-P(ODA-co-EHA) polymers with high EHA contents exhibited lower gelation temperatures because of the greater solvent compatibility with dodecane. The use of a PMMA65-b-(ODA10-co-EHA45) copolymer stabilizer (with the highest EHA content) gave PMMA dispersions that showed no gelation down to 4 °C and monodisperse cross-linked PMMA particles containing organic dyes (cyan, magenta, red, and black) giving colored particles across the size range of approximately 100–1300 nm

    Effect of ospemifene on moderate or severe symptoms of vulvar and vaginal atrophy.

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    Objectives To determine whether assessment of all moderate-to-severe symptoms at baseline gives a more accurate evaluation of the treatment effect of ospemifene in vulvovaginal atrophy (VVA) than the most bothersome symptom (MBS) approach. Methods Data were pooled from two pivotal phase-III clinical trials evaluating the efficacy and safety of oral ospemifene 60 mg/day for the treatment of symptoms of VVA (n = 1463 subjects). Symptoms of vaginal dryness, dyspareunia, and vaginal and/or vulvar irritation/itching reported as moderate or severe at baseline were evaluated. Clinically relevant differences between ospemifene and placebo were analyzed using a four-point severity scoring system and presented as improvement, substantial improvement, or relief. Results Subjects in these studies reported statistically significant improvement, substantial improvement, and relief for vaginal dryness (p \u3c 0.00001), dyspareunia (p \u3c 0.001) and statistically significant improvement and relief for vaginal and/or vulvar irritation/itching (p \u3c 0.01) from baseline to week 12 with ospemifene compared with placebo. A similar trend was observed for women who reported substantial improvement of vaginal and/or vulvar irritation/itching. Conclusions For drug registration purposes, the use of the MBS model is appealing because of its simplicity and ease of scientific validation. However, the MBS model may underestimate the total magnitude of the clinical benefit of ospemifene treatment for symptomatic women suffering from VVA

    Comparative analysis of the vaginal microbiome of pregnant women with either Trichomonas vaginalis or Chlamydia trachomatis

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    BACKGROUND:Although the significance of the human vaginal microbiome for health and disease is increasingly acknowledged, there is paucity of data on the differences in the composition of the vaginal microbiome upon infection with different sexually transmitted pathogens. METHOD:The composition of the vaginal bacterial community of women with Trichomonas vaginalis (TV, N = 18) was compared to that of women with Chlamydia trachomatis (CT, N = 14), and to that of controls (N = 21) (women negative for TV, CT and bacterial vaginosis). The vaginal bacterial composition was determined using high throughput sequencing with the Ion 16S metagenomics kit of the variable regions 2, 4 and 8 of the bacterial 16S ribosomal RNA gene from the vaginal swab DNA extract of the women. QIIME and R package "Phyloseq" were used to assess the α- and β-diversity and absolute abundance of the 16S rRNA gene per sample in the three groups. Differences in taxa at various levels were determined using the independent T-test. RESULTS:A total of 545 operational taxonomic units (OTUs) were identified in all the three groups of which 488 occurred in all three groups (core OTUs). Bacterial α-diversity, by both Simpson's and Shannon's indices, was significantly higher, (p = 0.056) and (p = 0.001) respectively, among women with either TV or CT than among controls (mean α-diversity TV-infected > CT-infected > Controls). At the genus level, women infected with TV had a significantly (p < 0.01) higher abundance of Parvimonas and Prevotella species compared to both controls and CT-infected women, whereas women infected with CT had a significantly (p < 0.05) higher abundance of Anaerococcus, Collinsella, Corynebacterium and Dialister. CONCLUSION:The vaginal microbiomes of TV and CT-infected women were markedly different from each other and from women without TV and CT. Future studies should determine whether the altered microbiomes are merely markers of disease, or whether they actively contribute to the pathology of the two genital infections

    Circumbinary MHD Accretion into Inspiraling Binary Black Holes

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    As 2 black holes bound to each other in a close binary approach merger their inspiral time becomes shorter than the characteristic inflow time of surrounding orbiting matter. Using an innovative technique in which we represent the changing spacetime in the region occupied by the orbiting matter with a 2.5PN approximation and the binary orbital evolution with 3.5PN, we have simulated the MHD evolution of a circumbinary disk surrounding an equal-mass non-spinning binary. Prior to the beginning of the inspiral, the structure of the circumbinary disk is predicted well by extrapolation from Newtonian results. The binary opens a low-density gap whose radius is roughly two binary separations, and matter piles up at the outer edge of this gap as inflow is retarded by torques exerted by the binary; nonetheless, the accretion rate is diminished relative to its value at larger radius by only about a factor of 2. During inspiral, the inner edge of the disk at first moves inward in coordination with the shrinking binary, but as the orbital evolution accelerates, the rate at which the inner edge moves toward smaller radii falls behind the rate of binary compression. In this stage, the rate of angular momentum transfer from the binary to the disk slows substantially, but the net accretion rate decreases by only 10-20%. When the binary separation is tens of gravitational radii, the rest-mass efficiency of disk radiation is a few percent, suggesting that supermassive binary black holes in galactic nuclei could be very luminous at this stage of their evolution. If the luminosity were optically thin, it would be modulated at a frequency that is a beat between the orbital frequency of the disk's surface density maximum and the binary orbital frequency. However, a disk with sufficient surface density to be luminous should also be optically thick; as a result, the periodic modulation may be suppressed.Comment: 54 pages, color figures, submitted to the Astrophysical Journal, a high resolution version and movies can be found at http://ccrg.rit.edu/~scn/cmhdaiibh

    Low-Frequency Oscillations in Global Simulations of Black Hole Accretion

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    We have identified the presence of large-scale, low-frequency dynamo cycles in a long-duration, global, magnetohydrodynamic (MHD) simulation of black hole accretion. Such cycles had been seen previously in local shearing box simulations, but we discuss their evolution over 1,500 inner disk orbits of a global pi/4 disk wedge spanning two orders of magnitude in radius and seven scale heights in elevation above/below the disk midplane. The observed cycles manifest themselves as oscillations in azimuthal magnetic field occupying a region that extends into a low-density corona several scale heights above the disk. The cycle frequencies are ten to twenty times lower than the local orbital frequency, making them potentially interesting sources of low-frequency variability when scaled to real astrophysical systems. Furthermore, power spectra derived from the full time series reveal that the cycles manifest themselves at discrete, narrow-band frequencies that often share power across broad radial ranges. We explore possible connections between these simulated cycles and observed low-frequency quasi-periodic oscillations (LFQPOs) in galactic black hole binary systems, finding that dynamo cycles have the appropriate frequencies and are located in a spatial region associated with X-ray emission in real systems. Derived observational proxies, however, fail to feature peaks with RMS amplitudes comparable to LFQPO observations, suggesting that further theoretical work and more sophisticated simulations will be required to form a complete theory of dynamo-driven LFQPOs. Nonetheless, this work clearly illustrates that global MHD dynamos exhibit quasi-periodic behavior on timescales much longer than those derived from test particle considerations.Comment: Version accepted to The Astrophysical Journal, 8 pages, 7 figure

    A novel strategy for the identification of antigens that are recognised by bovine MHC class I restricted cytotoxic T cells in a protozoan infection using reverse vaccinology

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    BACKGROUND: Immunity against the bovine protozoan parasite Theileria parva has previously been shown to be mediated through lysis of parasite-infected cells by MHC class I restricted CD8(+ )cytotoxic T lymphocytes. It is hypothesized that identification of CTL target schizont antigens will aid the development of a sub-unit vaccine. We exploited the availability of the complete genome sequence data and bioinformatics tools to identify genes encoding secreted or membrane anchored proteins that may be processed and presented by the MHC class I molecules of infected cells to CTL. RESULTS: Of the 986 predicted open reading frames (ORFs) encoded by chromosome 1 of the T. parva genome, 55 were selected based on the presence of a signal peptide and/or a transmembrane helix domain. Thirty six selected ORFs were successfully cloned into a eukaryotic expression vector, transiently transfected into immortalized bovine skin fibroblasts and screened in vitro using T. parva-specific CTL. Recognition of gene products by CTL was assessed using an IFN-γ ELISpot assay. A 525 base pair ORF encoding a 174 amino acid protein, designated Tp2, was identified by T. parva-specific CTL from 4 animals. These CTL recognized and lysed Tp2 transfected skin fibroblasts and recognized 4 distinct epitopes. Significantly, Tp2 specific CD8(+ )T cell responses were observed during the protective immune response against sporozoite challenge. CONCLUSION: The identification of an antigen containing multiple CTL epitopes and its apparent immunodominance during a protective anti-parasite response makes Tp2 an attractive candidate for evaluation of its vaccine potential

    Analysis of the transcriptome of the protozoan Theileria parva using MPSS reveals that the majority of genes are transcriptionally active in the schizont stage

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    Massively parallel signature sequencing (MPSS) was used to analyze the transcriptome of the intracellular protozoan Theileria parva. In total 1 095 000, 20 bp sequences representing 4371 different signatures were generated from T.parva schizonts. Reproducible signatures were identified within 73% of potentially detectable predicted genes and 83% had signatures in at least one MPSS cycle. A predicted leader peptide was detected on 405 expressed genes. The quantitative range of signatures was 4–52 256 transcripts per million (t.p.m.). Rare transcripts (<50 t.p.m.) were detected from 36% of genes. Sequence signatures approximated a lognormal distribution, as in microarray. Transcripts were widely distributed throughout the genome, although only 47% of 138 telomere-associated open reading frames exhibited signatures. Antisense signatures comprised 13.8% of the total, comparable with Plasmodium. Eighty five predicted genes with antisense signatures lacked a sense signature. Antisense transcripts were independently amplified from schizont cDNA and verified by sequencing. The MPSS transcripts per million for seven genes encoding schizont antigens recognized by bovine CD8 T cells varied 1000-fold. There was concordance between transcription and protein expression for heat shock proteins that were very highly expressed according to MPSS and proteomics. The data suggests a low level of baseline transcription from the majority of protein-coding genes

    Evaluating clinician acceptability of the prototype CanRisk tool for predicting risk of breast and ovarian cancer: A multi-methods study.

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    BACKGROUND:There is a growing focus on the development of multi-factorial cancer risk prediction algorithms alongside tools that operationalise them for clinical use. BOADICEA is a breast and ovarian cancer risk prediction model incorporating genetic and other risk factors. A new user-friendly Web-based tool (CanRisk.org) has been developed to apply BOADICEA. This study aimed to explore the acceptability of the prototype CanRisk tool among two healthcare professional groups to inform further development, evaluation and implementation. METHOD:A multi-methods approach was used. Clinicians from primary care and specialist genetics clinics in England, France and Germany were invited to use the CanRisk prototype with two test cases (either face-to-face with a simulated patient or via a written vignette). Their views about the tool were examined via a semi-structured interview or equivalent open-ended questionnaire. Qualitative data were subjected to thematic analysis and organised around Sekhon's Theoretical Framework of Acceptability. RESULTS:Seventy-five clinicians participated, 21 from primary care and 54 from specialist genetics clinics. Participants were from England (n = 37), France (n = 23) and Germany (n = 15). The prototype CanRisk tool was generally acceptable to most participants due to its intuitive design. Primary care clinicians were concerned about the amount of time needed to complete, interpret and communicate risk information. Clinicians from both settings were apprehensive about the impact of the CanRisk tool on their consultations and lack of opportunities to interpret risk scores before sharing them with their patients. CONCLUSIONS:The findings highlight the challenges associated with developing a complex tool for use in different clinical settings; they also helped refine the tool. This prototype may not have been versatile enough for clinical use in both primary care and specialist genetics clinics where the needs of clinicians are different, emphasising the importance of understanding the clinical context when developing cancer risk assessment tools
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