729 research outputs found

    FHIT gene therapy prevents tumor development in Fhit-deficient mice

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    The tumor suppressor gene FHIT spans a common fragile site and is highly susceptible to environmental carcinogens. FHIT inactivation and loss of expression is found in a large fraction of premaligant and malignant lesions. In this study, we were able to inhibit tumor development by oral gene transfer, using adenoviral or adenoassociated viral vectors expressing the human FHIT gene, in heterozygous Fhit+/- knockout mice, that are prone to tumor development after carcinogen exposure. We therefore suggest that FHIT gene therapy could be a novel clinical approach not only in treatment of early stages of cancer, but also in prevention of human cancer

    Dataset after seven years simulating hybrid energy systems with Homer Legacy

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    Homer Legacy software is a well-known software for simulation of small hybrid systems that can be used for both design and research. This dataset is a set of files generated by Homer Legacy bringing the simulation results of hybrid energy systems over the last seven years, as a consequence of the research work led by Dr. Alexandre Beluco, Federal University of Rio Grande do Sul, in southern Brazil. The data correspond to twelve papers published in the last seven years. Two of them describe hydro PV hybrid systems with photovoltaic panels operating on the water surface of reservoirs. One of these twelve papers suggests the modeling of hydropower plants with reservoirs and the other the modeling of pumped hydro storage, and a third still uses these models in a place that could receive both the two types of hydroelectric power plant. The other simulated hybrid systems include wind turbines, diesel generators, batteries, among other components. This data article describes the files that integrate this dataset and the papers that have been published presenting the hybrid systems under study and discussing the results. The files that make up this dataset are available on Mendeley Data repository at https://doi.org/10.17632/ybxsttf2by.2

    Midday measurements of leaf water potential and stomatal conductance are highly correlated with daily water use of Thompson Seedless grapevines

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    A study was conducted to determine the relationship between midday measurements of vine water status and daily water use of grapevines measured with a weighing lysimeter. Water applications to the vines were terminated on August 24th for 9 days and again on September 14th for 22 days. Daily water use of the vines in the lysimeter (ETLYS) was approximately 40 L vine−1 (5.3 mm) prior to turning the pump off, and it decreased to 22.3 L vine−1 by September 2nd. Pre-dawn leaf water potential (ΨPD) and midday Ψl on August 24th were −0.075 and −0.76 MPa, respectively, with midday Ψl decreasing to −1.28 MPa on September 2nd. Leaf g s decreased from ~500 to ~200 mmol m−2 s−1 during the two dry-down periods. Midday measurements of g s and Ψl were significantly correlated with one another (r = 0.96) and both with ETLYS/ETo (r = ~0.9). The decreases in Ψl, g s, and ETLYS/ETo in this study were also a linear function of the decrease in volumetric soil water content. The results indicate that even modest water stress can greatly reduce grapevine water use and that short-term measures of vine water status taken at midday are a reflection of daily grapevine water us

    Dupilumab significantly improves sleep in adults with atopic dermatitis: results from the 12-week placebo-controlled period of the 24-week phase 4 randomized double-blinded placebo-controlled DUPISTAD study

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    BACKGROUND Sleep disturbance is a prominent symptom of atopic dermatitis (AD) and can result in insomnia, daytime fatigue, drowsiness, reduced productivity and impaired quality of life (QoL). OBJECTIVES The Dupilumab Effect on Sleep in AD Patients (DUPISTAD) phase IV randomized double-blinded placebo-controlled study evaluated the impact of dupilumab treatment on sleep and other patient- and physician-reported outcomes. METHODS Adults with moderate-to-severe AD were randomized 2 : 1 to dupilumab 300 mg once every 2 weeks (q2w) or placebo for 12 weeks; concomitant topical corticosteroids were permitted. Patients subsequently entered an open-label phase and received dupilumab 300 mg q2w for a further 12 weeks. The primary endpoint was the percentage change in sleep quality from baseline to week 12, assessed using a novel numeric rating scale (NRS). Secondary and exploratory endpoints included percentage change in peak pruritus NRS (PP NRS), change in SCORing Atopic Dermatitis (SCORAD), SCORAD sleep visual analogue scale (VAS), Eczema Area and Severity Index, Patient-Reported Outcomes Measurement Information System (PROMIS) sleep-related impairment T-score and the Epworth Sleepiness Scale. Sleep diary and wrist actigraphy measurements were recorded throughout the study. RESULTS In total, 127 patients received dupilumab and 61 patients received placebo. Demographic and baseline disease characteristics were balanced between groups. Sleep quality NRS significantly improved in patients treated with dupilumab by week 12 vs. placebo [least squares mean of the difference (LSMD) -15.5%, P < 0.001]. PP NRS (LSMD -27.9%, P < 0.001), SCORAD (LSMD -15.1, P < 0.001), SCORAD sleep VAS (LSMD -2.1, P < 0.001) and PROMIS T-score (LSMD -3.6, P < 0.001) were also significantly improved at week 12 with dupilumab vs. placebo. The overall percentage of patients reporting treatment-emergent adverse events was lower in the dupilumab group (56.7%) than in the placebo group (67.2%). CONCLUSIONS Dupilumab significantly improved sleep quality and perception of sleep continuity, itch, metrics of AD severity and QoL in adults with moderate-to-severe AD, with an acceptable safety profile compared with placebo

    Cutaneous adverse events associated with disease-modifying treatment in multiple sclerosis: A systematic review

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    Glatiramer acetate and interferon-beta are approved first-line disease-modifying treatments (DMTs) for multiple sclerosis (MS). DMTs can be associated with cutaneous adverse events, which may influence treatment adherence and patient quality of life. In this systematic review, we aimed to provide an overview of the clinical spectrum and the incidence of skin reactions associated with DMTs. A systematic literature search was performed up to May 2011 in Medline, Embase, and Cochrane databases without applying restrictions in study design, language, or publishing date. Eligible for inclusion were articles describing any skin reaction related to DMTs in MS patients. Selection of articles and data extraction were performed by two authors independently. One hundred and six articles were included, of which 41 (39%) were randomized controlled trials or cohort studies reporting incidences of mainly local injection-site reactions. A large number of patients had experienced some form of localized injection-site reaction: up to 90% for those using subcutaneous formulations and up to 33% for those using an intramuscular formulation. Sixty-five case-reports involving 106 MS patients described a wide spectrum of cutaneous adverse events, the most frequently reported being lipoatrophy, cutaneous necrosis and ulcers, and various immune-mediated inflammatory skin diseases. DMTs for MS are frequently associated with local injection-site reactions and a wide spectrum of generalized cutaneous adverse events, in particular, the subcutaneous formulations. Although some of the skin reactions may be severe and persistent, most of them are mild and do not require cessation of DMT

    How do hospitals respond to feedback about blood transfusion practice? A multiple case study investigation

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    National clinical audits play key roles in improving care and driving system-wide change. However, effects of audit and feedback depend upon both reach (e.g. relevant staff receiving the feedback) and response (e.g. staff regulating their behaviour accordingly). This study aimed to investigate which hospital staff initially receive feedback and formulate a response, how feedback is disseminated within hospitals, and how responses are enacted (including barriers and enablers to enactment). Using a multiple case study approach, we purposively sampled four UK hospitals for variation in infrastructure and resources. We conducted semi-structured interviews with staff from transfusion-related roles and observed Hospital Transfusion Committee meetings. Interviews and analysis were based on the Theoretical Domains Framework of behaviour change. We coded interview transcripts into theoretical domains, then inductively identified themes within each domain to identify barriers and enablers. We also analysed data to identify which staff currently receive feedback and how dissemination is managed within the hospital. Members of the hospital's transfusion team initially received feedback in all cases, and were primarily responsible for disseminating and responding, facilitated through the Hospital Transfusion Committee. At each hospital, key individuals involved in prescribing transfusions reported never having received feedback from a national audit. Whether audits were discussed and actions explicitly agreed in Committee meetings varied between hospitals. Key enablers of action across all cases included clear lines of responsibility and strategies to remind staff about recommendations. Barriers included difficulties disseminating to relevant staff and needing to amend feedback to make it appropriate for local use. Appropriate responses by hospital staff to feedback about blood transfusion practice depend upon supportive infrastructures and role clarity. Hospitals could benefit from support to disseminate feedback systematically, particularly to frontline staff involved in the behaviours being audited, and practical tools to support strategic decision-making (e.g. action-planning around local response to feedback)
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