477 research outputs found

    Defining the role of cellular immune signatures in diagnostic evaluation of suspected tuberculosis

    Get PDF
    BACKGROUND: Diagnosis of paucibacillary tuberculosis (TB) including extrapulmonary TB is a significant challenge, particularly in high-income, low-incidence settings. Measurement of Mycobacterium tuberculosis (Mtb)-specific cellular immune signatures by flow cytometry discriminates active TB from latent TB infection (LTBI) in case-control studies; however, their diagnostic accuracy and clinical utility in routine clinical practice is unknown. METHODS: Using a nested case-control study design within a prospective multicenter cohort of patients presenting with suspected TB in England, we assessed diagnostic accuracy of signatures in 134 patients who tested interferon-gamma release assay (IGRA)-positive and had final diagnoses of TB or non-TB diseases with coincident LTBI. Cellular signatures were measured using flow cytometry. RESULTS: All signatures performed less well than previously reported. Only signatures incorporating measurement of phenotypic markers on functional Mtb-specific CD4 T cells discriminated active TB from non-TB diseases with LTBI. The signatures measuring HLA-DR+IFNγ + CD4 T cells and CD45RA-CCR7-CD127- IFNγ -IL-2-TNFα + CD4 T cells performed best with 95% positive predictive value (95% confidence interval, 90-97) in the clinically challenging subpopulation of IGRA-positive but acid-fast bacillus (AFB) smear-negative TB suspects. CONCLUSIONS: Two cellular immune signatures could improve and accelerate diagnosis in the challenging group of patients who are IGRA-positive, AFB smear-negative, and have paucibacillary TB

    Ethylene supports colonization of plant roots by the mutualistic fungus Piriformospora indica

    Get PDF
    The mutualistic basidiomycete Piriformospora indica colonizes roots of mono- and dicotyledonous plants, and thereby improves plant health and yield. Given the capability of P. indica to colonize a broad range of hosts, it must be anticipated that the fungus has evolved efficient strategies to overcome plant immunity and to establish a proper environment for nutrient acquisition and reproduction. Global gene expression studies in barley identified various ethylene synthesis and signaling components that were differentially regulated in P. indica-colonized roots. Based on these findings we examined the impact of ethylene in the symbiotic association. The data presented here suggest that P. indica induces ethylene synthesis in barley and Arabidopsis roots during colonization. Moreover, impaired ethylene signaling resulted in reduced root colonization, Arabidopsis mutants exhibiting constitutive ethylene signaling, -synthesis or ethylene-related defense were hyper-susceptible to P. indica. Our data suggest that ethylene signaling is required for symbiotic root colonization by P. indica

    Surface chemical and color characterization of juvenile tectona grandis wood subjected to steam-drying treatments

    Get PDF
    ArtículoThe color of Tectona grandis wood is an attribute that favors its commercialization, however, wood color from fast-growth plantation trees is clear and lacks uniformity. The aim of this work is to characterize steamed teak wood by means of the Fourier transform infrared spectroscopy (FTIR) and L a b color systems. Two moisture conditions (green and 50%) and two grain patterns (°at and quarter) of boards were analyzed through the application of di®erent steaming times (0, 3, 6, 9, 12, 15 and 18 h). The FTIR results showed that the bands at 1158, 1231, 1373 and 1419 cm 1 did not show any change with steaming, whereas the bands at 1053, 1108, 1453, 1506, 1536, 1558, 1595, 1652, 1683, 1700 and 1733 cm 1 presented a decrease in the intensity with the steaming time. The band at 1318 cm 1 was the only one that increased. Lightness (L ) was the most a®ected parameter, followed by yellowness (b ), while redness (a ) showed the smallest change. Surface color change ( E ) presented the lowest value between 3 h and 6 h of steam-drying in the boards with °at grain, whereas for boards with quarter grain, the smallest E value was obtained after 18 h of steaming

    Global treatment patterns and outcomes among patients with recurrent and/or metastatic head and neck squamous cell carcinoma: Results of the GLANCE H&N study.

    Get PDF
    OBJECTIVES:Given a lack of universally-accepted standard-of-care treatment for patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), study objectives were to assess treatment utilization and survival outcomes for R/M HNSCC in the real-world setting. MATERIALS AND METHODS:A multi-site retrospective chart review was conducted in Europe (Germany, United Kingdom, Italy, Spain), Asia Pacific (Australia, South Korea, Taiwan), and Latin/North America (Brazil and Canada) to identify patients who initiated first-line systemic therapy for R/M HNSCC between January 2011 and December 2013. Patients were followed through December 2015 to collect clinical characteristics, treatment and survival data. RESULTS:Among 733 R/M HNSCC patients across 71 sites, median age was 60 years (inter-quartile range 54-67), 84% male, and 70% Eastern Cooperative Oncology Group performance status 0-1; 32% had oral cavity and 30% oropharyngeal cancers. The most common first-line regimen across all countries consisted of platinum-based combinations (73%), including platinum + 5-fluorouracil (5-FU) (26%), cetuximab + platinum ± 5-FU (22%), or taxane + platinum ± 5-FU (16%). However, use of different platinum-based combinations varied substantially; administration of cetuximab + platinum ± 5-FU was frequent in Italy (81%), Germany (46%) and Spain (38%), whereas use in other countries was limited. Median follow-up was 22.6 months (95% confidence interval [CI]: 21.5-24.6 months). Median real-world overall survival was only 8.0 months (95% CI: 7.0-8.0), with one-year survival reaching only 30.9% (95% CI: 27.5-34.3). CONCLUSION:Systemic therapies used in clinical practice for patients with R/M HNSCC vary substantially across countries. Prognosis remains poor in this patient population, highlighting the need for newer, more efficacious treatments

    Ethylene- and pathogen-inducible Arabidopsis acyl-CoA-binding protein 4 interacts with an ethylene-responsive element binding protein

    Get PDF
    Six genes encode proteins with acyl-CoA-binding domains in Arabidopsis thaliana. They are the small 10-kDa cytosolic acyl-CoA-binding protein (ACBP), membrane-associated ACBP1 and ACBP2, extracellularly-targeted ACBP3, and kelch-motif containing ACBP4 and ACBP5. Here, the interaction of ACBP4 with an A. thaliana ethylene-responsive element binding protein (AtEBP), identified in a yeast two-hybrid screen, was confirmed by co-immunoprecipitation. The subcellular localization of ACBP4 and AtEBP, was addressed using an ACBP4:DsRed red fluorescent protein fusion and a green fluorescent protein (GFP):AtEBP fusion. Transient expression of these autofluoresence-tagged proteins in agroinfiltrated tobacco leaves, followed by confocal laser scanning microscopy, indicated their co-localization predominantly at the cytosol which was confirmed by FRET analysis. Immuno-electron microscopy on Arabidopsis sections not only localized ACBP4 to the cytosol but also to the periphery of the nucleus upon closer examination, perhaps as a result of its interaction with AtEBP. Furthermore, the expression of ACBP4 and AtEBP in Northern blot analyses was induced by the ethylene precursor 1-aminocyclopropane-1-carboxylic acid, methyl jasmonate treatments, and Botrytis cinerea infection, suggesting that the interaction of ACBP4 and AtEBP may be related to AtEBP-mediated defence possibly via ethylene and/or jasmonate signalling

    Calibrating ensemble reliability whilst preserving spatial structure

    Get PDF
    Ensemble forecasts aim to improve decision-making by predicting a set of possible outcomes. Ideally, these would provide probabilities which are both sharp and reliable. In practice, the models, data assimilation and ensemble perturbation systems are all imperfect, leading to deficiencies in the predicted probabilities. This paper presents an ensemble post-processing scheme which directly targets local reliability, calibrating both climatology and ensemble dispersion in one coherent operation. It makes minimal assumptions about the underlying statistical distributions, aiming to extract as much information as possible from the original dynamic forecasts and support statistically awkward variables such as precipitation. The output is a set of ensemble members preserving the spatial, temporal and inter-variable structure from the raw forecasts, which should be beneficial to downstream applications such as hydrological models. The calibration is tested on three leading 15-d ensemble systems, and their aggregation into a simple multimodel ensemble. Results are presented for 12 h, 1° scale over Europe for a range of surface variables, including precipitation. The scheme is very effective at removing unreliability from the raw forecasts, whilst generally preserving or improving statistical resolution. In most cases, these benefits extend to the rarest events at each location within the 2-yr verification period. The reliability and resolution are generally equivalent or superior to those achieved using a Local Quantile-Quantile Transform, an established calibration method which generalises bias correction. The value of preserving spatial structure is demonstrated by the fact that 3×3 averages derived from grid-scale precipitation calibration perform almost as well as direct calibration at 3×3 scale, and much better than a similar test neglecting the spatial relationships. Some remaining issues are discussed regarding the finite size of the output ensemble, variables such as sea-level pressure which are very reliable to start with, and the best way to handle derived variables such as dewpoint depression

    Demographic, socioeconomic, and sociocultural factors associated with any breastfeeding in homeless mothers

    Get PDF
    In high‐income countries, breastfeeding has been shown to be positively associated with socioeconomic position. However, less is known about breastfeeding practices and their associated factors among extremely disadvantaged populations. We aimed to assess the associations of cultural origins and socioeconomic factors with any breastfeeding initiation and duration in homeless families. We analyzed data from 456 children aged 6 months to 5 years from the cross‐sectional ENFAMS survey, conducted in 2013 among a random sample of homeless families in shelters in the Greater Paris area. Data were collected by bilingual interviewers in 17 languages. Four nested multivariable robust Poisson regression models were run in a hierarchical framework to determine the factors associated with breastfeeding initiation and with any breastfeeding for 6 months or more. Most of the children (86.0%) had previously been or were currently being breastfed at the time of the survey; 58.9% were fed with breast milk ≥6 months. A higher maternal age and African origin were positively associated with breastfeeding ≥6 months, although the relation to the region of origin was moderated by education level. Migration to escape war, unrest or other violence and the child's birth in France were inversely associated with breastfeeding ≥6 months. Any breastfeeding by these homeless mothers seems influenced predominantly by their cultural origin and complicated by a difficult migration trajectory. The possible influence of poor material circumstances and cumulative hardship should encourage interventions targeted at homeless mothers that emphasize social/family support with a commitment to improving the family's living conditions
    corecore