125 research outputs found

    MAN AND THE FACTORS OF ENVIRONMENT

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    MYOCARDIOFIBROSIS IN CHRONIC CUPRIC SULFATE INTOXICATION

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    A Clarke–Ledyaev Type Inequality for Certain Non–Convex Sets

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    We consider the question whether the assumption of convexity of the set involved in Clarke-Ledyaev inequality can be relaxed. In the case when the point is outside the convex hull of the set we show that Clarke-Ledyaev type inequality holds if and only if there is certain geometrical relation between the point and the set

    LATE CHANGES IN THE GONADS OF MALE WHITE RATS UPON COMBINED TREATMENT WITH LOW FREQUENCY VIBRATIONS AND RAMROD INTOXICATION

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    FREQUENCY AND FORMS OF INNATE MALFORMATIONS

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    Cost-Effectiveness Model for Neovascular Age-Related Macular Degeneration: Comparing Early and Late Treatment with Pegaptanib Sodium Based on Visual Acuity

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    AbstractObjectiveTo compare the cost-effectiveness of pegaptanib and usual care within three distinct cohorts of subfoveal neovascular age-related macular degeneration (NV-AMD) patients, that is, those with early, moderate, and late disease, using a comprehensive economic model.MethodsA Markov framework was used to model lifetime movement of a subfoveal NV-AMD cohort through health states based on visual acuity. The model takes a US payer perspective of patients over the age of 65 years. Clinical efficacy was based on published results for the 0.3 mg pegaptanib and usual care groups. Expert interviews were conducted to determine adverse event treatment patterns and vision rehabilitation resource use. Incidence and costs of comorbidities such as depression and fractures associated with the effects of declining visual acuity were based on our previously published analysis of Medicare data. Transition probabilities were derived from published clinical trial data for each 3-month cycle. Utilities were derived from published sources. Three runs of the model were conducted with cohorts of newly diagnosed patients. Patients were classified as having early, moderate, or late NV-AMD defined as visual acuity in the better-seeing eye of 20/40 to more than 20/80, 20/80 to more than 20/200, and 20/200 to more than 20/400, respectively. Costs and outcomes were discounted 3.0% per annum.ResultsIncremental costs per vision-year gained and per quality-adjusted life-year (QALY) gained for early NV-AMD patients were approximately one-third those of patients with late disease (15,279vs.15,279 vs. 57,230 and 36,282vs.36,282 vs. 132,381, respectively). On average, patients treated early with either pegaptanib or usual care incurred lower lifetime total direct costs than those treated later. Sensitivity analysis showed that base-case incremental costs per QALY gained for pegaptanib versus usual care were relatively robust.ConclusionsFor patients with subfoveal NV-AMD, treatment with pegaptanib should be started as early as possible to maximize the clinical and economic benefits

    Fluorescence analysis of the Hansenula polymorpha peroxisomal targeting signal-1 receptor, Pex5p

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    Correct sorting of newly synthesized peroxisomal matrix proteins is dependent on a peroxisomal targeting signal (PTS). So far two PTSs are known. PTS1 consists of a tripeptide that is located at the extreme C terminus of matrix proteins and is specifically recognized by the PTS1-receptor Pex5p. We studied Hansenula polymorpha Pex5p (HpPex5p) using fluorescence spectroscopy. The intensity of Trp fluorescence of purified HpPex5p increased by 25% upon shifting the pH from pH 6.0 to pH 7.2. Together with the results of fluorescence quenching by acrylamide, these data suggest that the conformation of HpPex5p differs at these two pH values. Fluorescence anisotropy decay measurements revealed that the pH affected the oligomeric state of HpPex5p, possibly from monomers/dimers at pH 6.0 to larger oligomeric forms at pH 7.2. Addition of dansylated peptides containing a PTS1, caused some shortening of the average fluorescence lifetime of the Trp residues, which was most pronounced at pH 7.2. Our data are discussed in relation to a molecular model of HpPex5p based on the three-dimensional structure of human Pex5p
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