3,532 research outputs found

    In Vitro and In Vivo Characterization of a Fully Felinized Therapeutic Anti-Nerve Growth Factor Monoclonal Antibody for the Treatment of Pain in Cats

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    BACKGROUND: Limited options are available for the treatment of pain in cats. Monoclonal antibodies (mAbs) that neutralize nerve growth factor (NGF) have demonstrated analgesic capacity in rodent models, people with osteoarthritis, and dogs with degenerative joint disease. HYPOTHESIS/OBJECTIVES: This study describes the design and characterization of a fully felinized anti-NGF monoclonal antibody. In vitro potency, pharmacokinetics, and the ability of the antibody to treat pain in a self-resolving, acute inflammation model were investigated in cats. ANIMALS: Thirty-eight cats at a research colony at Charles River Laboratories, Ireland. METHODS: Felinized anti-NGF mAb, NV-02, was produced using a complementary DNA (cDNA)-based method (PETization). Purified NV-02 was tested for affinity, potency, and immunoreactivity in vitro, then for safety and plasma pharmacokinetic distribution in vivo, and analgesic efficacy in a model of kaolin-induced inflammatory pain. RESULTS: Anti-NGF mAb, NV-02 neutralized NGF with high affinity and potency and did not bind complement. NV-02-administered SC had a plasma half-life of 7-15 days and was well tolerated at dosages up to 28 mg/kg. A dosage of 2 mg/kg NV-02 SC significantly decreased signs of lameness on day 2 (P = .0027), day 3 (P = .016), day 4, (P = .0063), day 5 (P = .0085), day 6 (P = .0014), and day 7 (P = .0034) after induction of inflammation. CONCLUSIONS AND CLINICAL IMPORTANCE: The high affinity, long plasma half-life, safety, and analgesic efficacy of felinized anti-NGF mAb (NV-02) support further investigation of the analgesic potential of this antibody in the cat

    Risks Factors for Infections with Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae at a Tertiary Care University Hospital in Switzerland

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    Abstract : Background: : There are considerable geographical differencesin the occurrence of extended-spectrum beta-lactamase(ESBL)-producing bacteria, both in the community and in thehospital setting. Our aim was to assess risk factors forbloodstream, urinary tract, and vascular catheter-associatedinfections with ESBL-producing Escherichia coli and Klebsiellapneumoniae at a tertiary care hospital in a low-prevalencecountry. Methods: : We performed a case-control study comparing 58patients with infections due to ESBL-producing E. coli orK. pneumoniae vs 116 controls with infections due to non-ESBL producing organisms at the University Hospital Zurich,Switzerland, between 1 July 2005 and 30 June 2007. Results: : Cases included 15 outpatients and 43 inpatients.Multivariable analyses found three risk factors for ESBL-producingisolates: begin of symptoms or recent antibioticpre-treatment in a foreign country (odds ratio [OR] 27.01,95% confidence interval [CI] 2.38-1,733.28], p = 0.042),antibiotic therapy within the year preceding the isolation ofthe ESBL-producing strain (OR 2.88, 95% CI 1.13-8.49,p = 0.025), and mechanical ventilation (OR 10.56, 95% CI1.06-579.10, p = 0.042). Conclusions: : The major risk factors for infections due toESBL-producing bacteria were travel in high-prevalencecountries, prior antibiotic use, and mechanical ventilationduring a stay in the intensive care unit. Community-acquiredinfections were documented in 17% of the patients.An early identification of risk factors is crucial to providingthe patients an optimal empiric antibiotic therapy and tokeep the use of carbapenems to a minimu

    Color-tailored polymer light emitting diodes including emissive colloidal particles and method of forming same

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    Color-tailored and white-light emitting polymer colloid-based OLEDs are disclosed. Devices include electroluminescent (EL) colloidal conductive polymer systems that can include EL dyes or other EL materials. Systems can sequester multiple EL components in different colloids in a single emissive layer of an EL device with little or no appreciable energy transfer between colloids. Devices can exhibit tailored emissions over a broad range of wavelengths through mixing of, e.g., red, green and blue PLED colloids. Disclosed methods including incorporation of one or more electroluminescent dyes into a semiconductive EL polymer colloid that can isolate the dyes and prevent energy transfer while retaining individual color emission

    Implicit Beliefs About Change: A Theory-Grounded Measure Applied to Community Organizations Serving Children, Youth, and Families

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    The aim of this study was to design and evaluate a theory-grounded measure that taps staff beliefs about the possibility for change in an organization which serves children, youth and families at the community level. The rationale for measuring staff beliefs about change derived from a motivation theory that features two contrasting beliefs structures (entity vs. incremental), and the goals and behavioral dispositions associated with each (Dweck & Leggett, 1988). Twenty-nine individuals associated with the community-based organization completed the newly developed Implicit Beliefs About Change Scale (IBACS) and participatedi n a semi-structured interview. Quantitative analyses indicated that the IBACS has good internal consistency, and yields sufficient response variance. Content analysis of the semi-structured interviews, used to assess the scale\u27s construct validity, uncovered distinctive and theory-consistent behavioral dispositions among those staff members whose beliefs regarding change could be characterized as either incremental or entity in nature. Implications for staff development and future research are discussed

    Aerodynamic Characteristics of Two Waverider-Derived Hypersonic Cruise Configurations

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    An evaluation was made on the effects of integrating the required aircraft components with hypersonic high-lift configurations known as waveriders to create hypersonic cruise vehicles. Previous studies suggest that waveriders offer advantages in aerodynamic performance and propulsion/airframe integration (PAI) characteristics over conventional non-waverider hypersonic shapes. A wind-tunnel model was developed that integrates vehicle components, including canopies, engine components, and control surfaces, with two pure waverider shapes, both conical-flow-derived waveriders for a design Mach number of 4.0. Experimental data and limited computational fluid dynamics (CFD) solutions were obtained over a Mach number range of 1.6 to 4.63. The experimental data show the component build-up effects and the aerodynamic characteristics of the fully integrated configurations, including control surface effectiveness. The aerodynamic performance of the fully integrated configurations is not comparable to that of the pure waverider shapes, but is comparable to previously tested hypersonic models. Both configurations exhibit good lateral-directional stability characteristics

    Molecular characterisation of congenital myasthenic syndromes in Southern Brazil

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    Objective To perform genetic testing of patients with congenital myasthenic syndromes (CMS) from the Southern Brazilian state of Parana. Patients and methods Twenty-five CMS patients from 18 independent families were included in the study. Known CMS genes were sequenced and restriction digest for the mutation RAPSN p.N88K was performed in all patients. Results We identified recessive mutations of CHRNE in ten families, mutations in DOK7 in three families and mutations in COLQ, CHRNA1 and CHRNB1 in one family each. The mutation CHRNE c. 70insG was found in six families. We have repeatedly identified this mutation in patients from Spain and Portugal and haplotype studies indicate that CHRNE c. 70insG derives from a common ancestor. Conclusions Recessive mutations in CHRNE are the major cause of CMS in Southern Brazil with a common mutation introduced by Hispanic settlers. The second most common cause is mutations in DOK7. The minimum prevalence of CMS in Parana is 0.18/100 000
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