239 research outputs found

    Water absorption in epoxy resins by electronic energy transfert

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    Presentación de Póster: Sesión C: Paper presentado en el Congreso "Polymers in the Third Millenium", 2-6 de septiembre de 2001 en Montpellier (Francia).Poster presentation: Session C: Paper presented at the Polymers in the Third Millennium Conference, 2–6 September, 2001, Montpellier, FranceWater absorption of an epoxy resin was studied by steady-state fluorescence spectroscopy and gravimetry. It was found that the intrinsic emission of the epoxy resin could be modified selecting an adequate excitation wavelength. The epoxy component of the resin was labelled with a trans-4-nitro-4′-aminostilbene fluorescent probe. Using an excitation wavelength of 340 nm it was possible to induce energy transfer to the suitable acceptor trans-4-nitro-4′-dialkylaminostilbene (NDAS). The relative fluorescence intensity /₄₃₃/ /₅₉₆ was used as a convenient means to follow the quenching effect of water on the emission of NDAS when excited via energy transfer. It was found that both the relative intensity and the water content increase linearly with the square root of diffusion time in the early stages of the process. The apparent Stern–Volmer constants for the quenching of the fluorophore, when excited directly in a fluid THF solution or in the polymer matrix, were very similar but lower than when the fluorophore was excited via energy transfer. It was concluded that, at least in the early stages of the water diffusion process, the interchromophoric distance should increase.Authors gratefully acknowledge project BE97-4472 (Brite EuRam) and to CAM (Pricit, Programa Grupos Estratégicos) for financial support

    Knowledge, attitude and practices of Swiss dairy farmers towards intramammary antimicrobial use and antimicrobial resistance : A latent class analysis

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    Understanding farmers’ mindsets is important to improve antimicrobial stewardship in the dairy industry. This cross-sectional study aimed to determine farmers’ knowledge, attitude, and practices with respect to lactational intramammary antimicrobial use (AMU) and antimicrobial resistance (AMR) in Swiss dairy herds. Based on their approach towards subclinical mastitis (SCM) and non-severe cases of clinical mastitis (CM), subgroups of farmers were identified and compared regarding their knowledge, attitude and practices towards AMU and AMR. After conducting qualitative interviews to develop a questionnaire, an online survey was sent to 1296 randomly selected Swiss dairy farmers. Information was gathered on demographic data and farmers’ knowledge, attitude, and practices towards AMU and AMR. A latent class analysis was performed to identify subgroups of farmers based on management of SCM and non-severe CM cases. Based on the results of 542 completed questionnaires, poor knowledge with respect to AMU and AMR was identified, as well as discrepancies between farmers’ perceptions and their actual practices. Farmers approached cows with SCM and non-severe CM similarly, indicating they perceived both mastitis states as the same disease. Intramammary antimicrobial products containing cefquinome, which is a highest priority critically important antimicrobial, were among the 3 most commonly applied intramammary antimicrobials. Five latent classes of farmers were identified based on their management towards SCM and non-severe CM. One group of farmers (18.5% of respondents) indicated that they did not treat those mastitis cases, one group only treated SCM cases (13.8% of respondents), one group only treated non-severe CM cases (28.6% of respondents) and the largest group treated both mastitis states (39.1% of respondents). The latter group was subdivided into a latent class of farmers following guidelines for AMU/AMR (25.5% of respondents) and a group of farmers that were not strictly following these guidelines (13.7% of respondents). Regional differences between farmers, according to altitude and language region, explained some of the variation in latent class membership. Latent class membership was associated with farmers’ attitude to use antimicrobials as little as possible and with using antimicrobials only after performing bacteriological and susceptibility testing. This study gave detailed insight into Swiss farmers’ knowledge, attitude, and practices regarding AMU and AMR and provides opportunities to improve antimicrobial stewardship in Swiss dairy herds. The identified groups of farmers, based on their management practices regarding SCM and non-severe CM, may help to design tailored intervention strategies for improving prudent AMU in the heterogeneous population of dairy farmers in Switzerland.</p

    Randomized feasibility trial of the Scleroderma Patient-centered Intervention Network hand exercise program (SPIN-HAND): study protocol

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    Background: Significant functional impairment of the hands is nearly universal in systemic sclerosis (SSc, scleroderma). Hand exercises may improve hand function, but developing, testing and disseminating rehabilitation interventions in SSc is challenging. The Scleroderma Patient-centered Intervention Network (SPIN) was established to address this issue and has developed an online hand exercise program to improve hand function for SSc patients (SPIN-HAND). The aim of the proposed feasibility trial is to evaluate the feasibility of conducting a full-scale randomized controlled trial (RCT) of the SPIN-HAND intervention. Design and methods: The SPIN-HAND feasibility trial will be conducted via the SPIN Cohort. The SPIN Cohort was developed as a framework for embedded pragmatic trials using the cohort multiple RCT design. In total, 40 English-speaking SPIN Cohort participants with at least mild hand function limitations (Cochin Hand Function Scale ≥3) and an indicated interest in using an online hand-exercise intervention will be randomized with a 1:1 ratio to be offered to use the SPIN-HAND program or usual care for 3 months. The primary aim is to evaluate the trial implementation processes, required resources and management, scientific aspects, and participant acceptability and usage of the SPIN-HAND program. Discussion: The SPIN-HAND exercise program is a self-help tool that may improve hand function in patients with SSc. The SPIN-HAND feasibility trial will ensure that trial methodology is robust, feasible, and consistent with trial participant expectations. The results will guide adjustments that need to be implemented before undertaking a full-scale RCT of the SPIN-HAND program. Trial registration: ClinicalTrials.gov Identifier: NCT03092024.Canadian Institutes of Health Research(undefined

    Transcriptional repressor ZEB2 promotes terminal differentiation of CD8⁺ effector and memory T cell populations during infection

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    ZEB2 is a multi-zinc-finger transcription factor known to play a significant role in early neurogenesis and in epithelial-mesenchymal transition-dependent tumor metastasis. Although the function of ZEB2 in T lymphocytes is unknown, activity of the closely related family member ZEB1 has been implicated in lymphocyte development. Here, we find that ZEB2 expression is up-regulated by activated T cells, specifically in the KLRG1(hi) effector CD8(+) T cell subset. Loss of ZEB2 expression results in a significant loss of antigen-specific CD8(+) T cells after primary and secondary infection with a severe impairment in the generation of the KLRG1(hi) effector memory cell population. We show that ZEB2, which can bind DNA at tandem, consensus E-box sites, regulates gene expression of several E-protein targets and may directly repress Il7r and Il2 in CD8(+) T cells responding to infection. Furthermore, we find that T-bet binds to highly conserved T-box sites in the Zeb2 gene and that T-bet and ZEB2 regulate similar gene expression programs in effector T cells, suggesting that T-bet acts upstream and through regulation of ZEB2. Collectively, we place ZEB2 in a larger transcriptional network that is responsible for the balance between terminal differentiation and formation of memory CD8(+) T cells

    Revealing the intermediate-mass black hole at the heart of the dwarf galaxy NGC404 with sub-parsec resolution ALMA observations

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    We estimate the mass of the intermediate-mass black hole at the heart of the dwarf elliptical galaxy NGC 404 using Atacama Large Millimeter/submillimeter Array( ALMA) observations of the molecular interstellar medium at an unprecedented linear resolution of ≈0.5pc, in combination with existing stellar kinematic information. These ALMA observations reveal a central disc/torus of molecular gas clearly rotating around the black hole. This disc is surrounded by a morphologically and kinematically complex flocculent distribution of molecular clouds, that we resolve in detail. Continuum emission is detected from the central parts of NGC404, likely arising from the Rayleigh–Jeans tail of emission from dust around the nucleus, and potentially from dusty massive star-forming clumps at discrete locations in the disc. Several dynamical measurements of the black hole mass in this system have been made in the past, but they do not agree. We show here that both the observed molecular gas and stellar kinematics independently require a ≈5×105M black hole once we include the contribution of the molecular gas to the potential. Our best estimate comes from the high-resolution molecular gas kinematics, suggesting the black hole mass of this system is 5.5+4.1 −3.8×105 M (at the 99% confidence level), in good agreement with our revised stellar kinematic measurement and broadly consistent with extrapolations from the black hole mass–velocity dispersion and black hole mass – bulge mass relations. This highlights the need to accurately determine the mass and distribution of each dynamically important component around intermediate-mass black holes when attempting to estimate their masses

    International consensus guidelines for scoring the histopathological growth patterns of liver metastasis

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    BACKGROUND: Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs. METHODS: Guidelines for defining the HGPs were established by a large international team. To assess the validity of these guidelines, 12 independent observers scored a set of 159 liver metastases and interobserver variability was measured. In an independent cohort of 374 patients with colorectal liver metastases (CRCLM), the impact of HGPs on overall survival after hepatectomy was determined. RESULTS: Good-to-excellent correlations (intraclass correlation coefficient >0.5) with the gold standard were obtained for the assessment of the replacement HGP and desmoplastic HGP. Overall survival was significantly superior in the desmoplastic HGP subgroup compared with the replacement or pushing HGP subgroup (P=0.006). CONCLUSIONS: The current guidelines allow for reproducible determination of liver metastasis HGPs. As HGPs impact overall survival after surgery for CRCLM, they may serve as a novel biomarker for individualised therapies

    Exploratory 7-Tesla magnetic resonance spectroscopy in Huntington’s disease provides in vivo evidence for impaired energy metabolism

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    Huntington’s disease (HD) is a neurodegenerative genetic disorder that affects the brain. Atrophy of deep grey matter structures has been reported and it is likely that underlying pathologic processes occur before, or in concurrence with, volumetric changes. Measurement of metabolite concentrations in these brain structures has the potential to provide insight into pathological processes. We aim to gain understanding of metabolite changes with respect to the disease stage and pathophysiological changes. We studied five brain regions using magnetic resonance spectroscopy (MRS) using a 7-Tesla MRI scanner. Localized proton spectra were acquired to obtain six metabolite concentrations. MRS was performed in the caudate nucleus, putamen, thalamus, hypothalamus, and frontal lobe in 44 control subjects, premanifest gene carriers and manifest HD. In the caudate nucleus, HD patients display lower NAA (p = 0.009) and lower creatine concentration (p = 0.001) as compared to controls. In the putamen, manifest HD patients show lower NAA (p = 0.024), lower creatine concentration (p = 0.027), and lower glutamate (p = 0.013). Although absolute values of NAA, creatine, and glutamate were lower, no significant differences to controls were found in the premanifest gene carriers. The lower concentrations of NAA and creatine in the caudate nucleus and putamen of early manifest HD suggest deficits in neuronal integrity and energy metabolism. The changes in glutamate could support the excitotoxicity theory. These findings not only give insight into neuropathological changes in HD but also indicate that MRS can possibly be applied in future clinical trails to evaluate medication targeted at specific metabolic processes

    Cost of community-led larval source management and house improvement for malaria control: a cost analysis within a cluster-randomized trial in a rural district in Malawi

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    Background House improvement (HI) to prevent mosquito house entry, and larval source management (LSM) targeting aquatic mosquito stages to prevent development into adult forms, are promising complementary interventions to current malaria vector control strategies. Lack of evidence on costs and cost-effectiveness of community-led implementation of HI and LSM has hindered wide-scale adoption. This study presents an incremental cost analysis of community-led implementation of HI and LSM, in a cluster-randomized, factorial design trial, in addition to standard national malaria control interventions in a rural area (25,000 people), in southern Malawi. Methods In the trial, LSM comprised draining, filling, and Bacillus thuringiensis israelensis-based larviciding, while house improvement (henceforth HI) involved closing of eaves and gaps on walls, screening windows/ventilation spaces with wire mesh, and doorway modifications. Communities implemented all interventions. Costs were estimated retrospectively using the ‘ingredients approach’, combining ‘bottom-up’ and ‘top-down approaches’, from the societal perspective. To estimate the cost of independently implementing each intervention arm, resources shared between trial arms (e.g. overheads) were allocated to each consuming arm using proxies developed based on share of resource input quantities consumed. Incremental implementation costs (in 2017 US)arepresentedforHIonly,LSMonlyandHI+LSMarms.Insensitivityanalyses,theeffectofvaryingcostsofimportantinputsonestimatedcostswasexplored.ResultsThetotaleconomicprogrammecostsofcommunityledHIandLSMimplementationwas) are presented for HI-only, LSM-only and HI + LSM arms. In sensitivity analyses, the effect of varying costs of important inputs on estimated costs was explored. Results The total economic programme costs of community-led HI and LSM implementation was 626,152. Incremental economic implementation costs of HI, LSM and HI + LSM were estimated as 27.04,27.04, 25.06 and $33.44, per person per year, respectively. Project staff, transport and labour costs, but not larvicide or screening material, were the major cost drivers across all interventions. Costs were sensitive to changes in staff costs and population covered. Conclusions In the trial, the incremental economic costs of community-led HI and LSM implementation were high compared to previous house improvement and LSM studies. Several factors, including intervention design, year-round LSM implementation and low human population density could explain the high costs. The factorial trial design necessitated use of proxies to allocate costs shared between trial arms, which limits generalizability where different designs are used. Nevertheless, costs may inform planners of similar intervention packages where cost-effectiveness is known

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
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