49 research outputs found

    Comprehension of Abstract and Concrete Commands by High and Low Level Aphasic Subjects : Effects of Presentation Mode

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    This study examined the influence of three presentation modes (live voice, tape recorded, and videotape recorded) on aphasic subjects\u27 comprehension of concrete and abstract commands

    Comprehension in Severe Aphasia: A Second Look

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    Paradoxical Effects of Rapamycin on Experimental House Dust Mite-Induced Asthma

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    The mammalian target of rapamycin (mTOR) modulates immune responses and cellular proliferation. The objective of this study was to assess whether inhibition of mTOR with rapamycin modifies disease severity in two experimental murine models of house dust mite (HDM)-induced asthma. In an induction model, rapamycin was administered to BALB/c mice coincident with nasal HDM challenges for 3 weeks. In a treatment model, nasal HDM challenges were performed for 6 weeks and rapamycin treatment was administered during weeks 4 through 6. In the induction model, rapamycin significantly attenuated airway inflammation, airway hyperreactivity (AHR) and goblet cell hyperplasia. In contrast, treatment of established HDM-induced asthma with rapamycin exacerbated AHR and airway inflammation, whereas goblet cell hyperplasia was not modified. Phosphorylation of the S6 ribosomal protein, which is downstream of mTORC1, was increased after 3 weeks, but not 6 weeks of HDM-challenge. Rapamycin reduced S6 phosphorylation in HDM-challenged mice in both the induction and treatment models. Thus, the paradoxical effects of rapamycin on asthma severity paralleled the activation of mTOR signaling. Lastly, mediastinal lymph node re-stimulation experiments showed that treatment of rapamycin-naive T cells with ex vivo rapamycin decreased antigen-specific Th2 cytokine production, whereas prior exposure to in vivo rapamycin rendered T cells refractory to the suppressive effects of ex vivo rapamycin. We conclude that rapamycin had paradoxical effects on the pathogenesis of experimental HDM-induced asthma. Thus, consistent with the context-dependent effects of rapamycin on inflammation, the timing of mTOR inhibition may be an important determinant of efficacy and toxicity in HDM-induced asthma

    REQUITE: A prospective multicentre cohort study of patients undergoing radiotherapy for breast, lung or prostate cancer

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    Purpose: REQUITE aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy. The purpose of this article is to provide summary descriptive data. Methods: An international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017. Target recruitment was 5300 patients. Eligible patients had breast, prostate or lung cancer and planned potentially curable radiotherapy. Radiotherapy was prescribed according to local regimens, but centres used standardised data collection forms. Pre-treatment blood samples were collected. Patients were followed for a minimum of 12 (lung) or 24 (breast/prostate) months and summary descriptive statistics were generated. Results: The study recruited 2069 breast (99% of target), 1808 prostate (86%) and 561 lung (51%) cancer patients. The centralised, accessible database includes: physician-(47,025 forms) and patient-(54,901) reported outcomes; 11,563 breast photos; 17,107 DICOMs and 12,684 DVHs. Imputed genotype data are available for 4223 patients with European ancestry (1948 breast, 1728 prostate, 547 lung). Radiation-induced lymphocyte apoptosis (RILA) assay data are available for 1319 patients. DNA (n = 4409) and PAXgene tubes (n = 3039) are stored in the centralised biobank. Example prevalences of 2-year (1-year for lung) grade >= 2 CTCAE toxicities are 13% atrophy (breast), 3% rectal bleeding (prostate) and 27% dyspnoea (lung). Conclusion: The comprehensive centralised database and linked biobank is a valuable resource for the radiotherapy community for validating predictive models and biomarkers. Patient summary: Up to half of cancer patients undergo radiation therapy and irradiation of surrounding healthy tissue is unavoidable. Damage to healthy tissue can affect short-and long-term quality-of-life. Not all patients are equally sensitive to radiation "damage" but it is not possible at the moment to identify those who are. REQUITE was established with the aim of trying to understand more about how we could predict radiation sensitivity. The purpose of this paper is to provide an overview and summary of the data and material available. In the REQUITE study 4400 breast, prostate and lung cancer patients filled out questionnaires and donated blood. A large amount of data was collected in the same way. With all these data and samples a database and biobank were created that showed it is possible to collect this kind of information in a standardised way across countries. In the future, our database and linked biobank will be a resource for research and validation of clinical predictors and models of radiation sensitivity. REQUITE will also enable a better understanding of how many people suffer with radiotherapy toxicity

    Rock glaciers and mountain hydrology: A review

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    This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.In mountainous regions, climate change threatens cryospheric water resources, and understanding all components of the hydrological cycle is necessary for effective water resource management. Rockglaciers are climatically more resilient than glaciers and contain potentially hydrologically valuable ice volumes, and yet havereceived lessattention, even though rock glacier hydrologicalimportance may increase under future climate warming. In synthesising data from a range of global studies, we provide the first compre-hensive evaluation of the hydrological role played by rock glaciers. Weevaluate hydrological significanceover a range of temporal and spatial scales, alongsidethe complex multiple hydrological processes with which rock glaciers can interact diurnally, seasonally, annually, decadally and both at local and regional extents.We report that although no global-extent, complete inventory for rock glaciers exists currently, recent research efforts have greatly elaborated spatialcoverage.Using these research papers,we synthe-sise information on rock glacier spatial distribution, morphometric characteristics, surface and subsurface features, ice-storage and hydrological flow dynamics, water chemistry, and future resilience, from which we provide the first comprehensive evaluation of their hydrological contribution. We identify and discuss long-, intermediate-and short-term timescales for rock glacier storage, allowing a more balanced assess-ment of the contrasting perspectives regarding the relative significance of rock glacier-derived hydrological contributions compared to other water sources.We show that further empirical observations are required to gain a deeper hydrological understanding of rock glaciers, in terms of(i) their genesis and geomorpho-logical dynamics (ii) total ice/water volume; (iii) water discharge; and (iv) water quality. Lastly, we hypothesisethat at decadal and longer timescales, under future climate warming, degradation of ice within rock glaciers may represent an increasing hydrological contribution to downstream regions, and thus in-creased hydrological significance while rock glacier water stores persist.Royal Geographical SocietyNatural Environment Research Council (NERC

    Spatiotemporal variation in risk of Shigella infection in childhood : a global risk mapping and prediction model using individual participant data

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    BACKGROUND: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). METHODS: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. FINDINGS: 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio [OR]=0·81 [95% CI 0·76-0·86]) and open defecation decreased them by 18% (OR=0·82 [0·76-0·88]). INTERPRETATION: The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges-Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns. FUNDING: NASA, National Institutes of Health-The National Institute of Allergy and Infectious Diseases, and Bill & Melinda Gates Foundation.publishedVersionPeer reviewe

    Ordensneugründungen und Anpassungsvorgänge im spätmittelalterlichen Klosterwesen Prags, Breslaus und Krakaus. Festschrift Winfried Eberhard zum 65. Geburtstag

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    Rüther A. Ordensneugründungen und Anpassungsvorgänge im spätmittelalterlichen Klosterwesen Prags, Breslaus und Krakaus. Festschrift Winfried Eberhard zum 65. Geburtstag. In: Lambrecht K, Maner HC, Bahlcke J, eds. Konfessionelle Pluralität als Herausforderung. Koexistenz und Konflikt in Spätmittelalter und Früher Neuzeit. Leipzig : Leipziger Universitäts-Verlag ; 2006: 55-70
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