Dictionnaire historique et bibliographique, abrégé, des personnages illustres, célébres ou famoux de tous los siécles et de tous les pays du mondo, avec les dieux et les héros de la mythologie,

Mode of access: Internet.

Index-catalogue of medical and veterinary zoology.

Description based on: 22, pt. 1, published in Dec. 1978.

The Journal of speculative philosophy.

Editor: -Dec. 1893, Wm. T. Harris.

CYP2D6: a global analysis of phenotypic and genotypic variation in search of radical cure of Plasmodium vivax malaria

Thesis (Master's)--University of Washington, 2016-06

Population pharmacokinetics of hydroxychloroquine in patients with rheumatoid arthritis

Hydroxychloroquine (HCQ) is an antimalarial drug that is also used as a second-line treatment of rheumatoid arthritis (RA). Clinically, the use of HCQ is characterized by a long delay in the onset of action, and withdrawal of treatment is often a result of inefficacy rather than from toxicity. The slow onset of action can be attributed to the pharmacokinetics (PK) of HCQ, and wide interpatient variability is evident. Tentative relationships between concentration and effect have been made, but to date, no population PK model has been developed for HCQ. This study aimed to develop a population PK model including an estimation of the oral bioavailability of HCQ. In addition, the effects of the coadministration of methotrexate on the PK of HCQ were examined. Hydroxychloroquine blood concentration data were combined from previous pharmacokinetic studies in patients with rheumatoid arthritis. A total of 123 patients were studied, giving the data cohort from four previously published studies. Two groups of patients were included: 74 received hydroxychloroquine (HCQ) alone, and 49 received HCQ and methotrexate (MTX). All data analyses were carried out using the NONMEM program. A one-compartment PK model was supported, rather than a three-compartment model as previously published, probably because of the clustering of concentrations taken at the end of a dosing interval. The population estimate of bioavailability of 0.75 (0.07), n = 9, was consistent with literature values. The parameter values from the final model were: (Cl) over bar = 9.9 +/- 0.4 L/h, (V) over bar 605 +/- 91 L, (k(d)) over bar = 0.77 +/- 0.22 hours(-1), (t(tag)) over bar = 0.44 +/- 0.02 hours. Clearance was not affected by the presence of MTX, and, hence, steady-state drug concentrations and maintenance dosage requirements were similar. A population PK model was successfully developed for HCQ.

Effects of litter and fine root composition on their decomposition in a Rhodic Paleustalf under different land uses

Plant litter and fine roots are important in maintaining soil organic carbon (C) levels as well as for nutrient cycling. The decomposition of surface-placed litter and fine roots of wheat ( Triticum aestivum ), lucerne ( Medicago sativa ), buffel grass ( Cenchrus ciliaris ), and mulga ( Acacia aneura ), placed at 10-cm and 30-cm depths, was studied in the field in a Rhodic Paleustalf. After 2 years, = 60% of mulga roots and twigs remained undecomposed. The rate of decomposition varied from 4.2 year -1 for wheat roots to 0.22 year -1 for mulga twigs, which was significantly correlated with the lignin concentration of both tops and roots. Aryl+O-aryl C concentration, as measured by 13 C nuclear magnetic resonance spectroscopy, was also significantly correlated with the decomposition parameters, although with a lower R 2 value than the lignin concentration. Thus, lignin concentration provides a good predictor of litter and fine root decomposition in the field.

Lessons from an estivating frog: sparing muscle protein despite starvation and disuse

Long (6- to 9-mo) bouts of estivation in green-striped burrowing frogs lead to 28% atrophy of cruralis oxidative fibers (P < 0.05) and some impairment of in vitro gastrocnemius endurance (P < 0.05) but no significant deficit in maximal twitch force production. These data suggest the preferential atrophy of oxidative fibers at a rate slower than, but comparable to, laboratory disuse models. We tested the hypothesis that the frog limits atrophy by modulating oxidative stress. We assayed various proteins at the transcript level and verified these results for antioxidant enzymes at the biochemical level. Transcript data for NADH ubiquinone oxidoreductase subunit 1 (71% downregulated, P < 0.05) and ATP synthase (67% downregulated, P < 0.05) are consistent with mitochondrial quiescence and reduced oxidant production. Meanwhile, uncoupling protein type 2 transcription (P < 0.31), which is thought to reduce mitochondrial leakage of reactive oxygen species, was maintained. Total antioxidant defense of water-soluble (22.3 +/- 1.7 and 23.8 +/- 1.5 mu M/mu g total protein in control and estivator, respectively, P = 0.53) and membrane-bound proteins (31.5 +/- 1.9 and 42.1 +/- 7.3 mu M/mu g total protein in control and estivator, respectively, P = 0.18) was maintained, equivalent to a bolstering of defense relative to oxygen insult. This probably decelerates muscle atrophy by preventing accumulation of oxidative damage in static protein reserves. Transcripts of the mitochondrially encoded antioxidant superoxide dismutase type 2 ( 67% downregulated, P < 0.05) paralleled mitochondrial activity, whereas nuclear-encoded catalase and glutathione peroxidase were maintained at control values (P = 0.42 and P = 0.231), suggesting a dissonance between mitochondrial and nuclear antioxidant expression. Pyruvate dehydrogenase kinase 4 transcription was fourfold lower in estivators (P = 0.11), implying that, in contrast to mammalian hibernators, this enzyme does not drive the combustion of lipids that helps spare hypometabolic muscle.

A Penhorablidade do Direito de autor na Obra Cinematográfica

O Direito de Autor protege a criação intelectual e, do mesmo modo, protege a obra cinematográfica. A obra cinematográfica caracteriza-se pelo conjunto de obras do realizador, do autor do argumento e dos diálogos, e da banda musical, conforme os artigos 2º, nº 1 alínea f) e 22º, nº 1 do Código de Direito de Autor e Direitos Conexos. O Direito de Autor subdivide-se em direitos patrimoniais e direitos pessoais. Apenas os direitos patrimoniais são passíveis de sofrer alteração de titular. A obra intelectual, enquanto coisa incorpórea, é objeto de transmissão. E como objeto de transmissão ela é possível de ser penhorada apenas no conteúdo patrimonial. E esta questão não é pacífica pela doutrina no Ordenamento Jurídico Português, pois sendo os direitos morais intransmissíveis a utilização que se faça do conteúdo patrimonial pode colidir com estes direitos morais. Embora a penhora incida apenas sobre o conteúdo patrimonial, ela pode ser condicionada pelo exercício dos direitos morais. A questão de máxima importância prende-se no facto de, não havendo mais nada a penhorar, poder-se ou não penhorar o Direito de Exploração do Direito de Autor quando ele esteja na pessoa do criador e/ou quando esteja na pessoa de um terceiro. Outro problema que a obra cinematográfica suscita, prende-se com o facto de, sendo possível penhorar, em que medida é que vamos penhorar, pois verifica-se vários direitos de autor inseridos numa só obra. Ou seja, sobre a “obra cinematográfica” reconhecem-se vários autores e, além disso, integrados na obra cinematográfica reconhece-se a possibilidade de coexistirem várias obras suscetíveis de utilização autónoma, sobre os quais existem direitos de autor, com conteúdos patrimoniais e morais, distintos do que incide sobre a obra cinematográfica como um todo.

Ocular blood flow measurements in healthy human myopic eyes

Background. To evaluate the haemodynamic features of young healthy myopes and emmetropes, in order to ascertain the perfusion profile of human myopia and its relationship with axial length prior to reaching a degenerative state. Methods The retrobulbar, microretinal and pulsatile ocular blood flow (POBF) of one eye of each of twenty-two high myopes (N=22, mean spherical equivalent (MSE) =-5.00D), low myopes (N=22, MSE-1.00 to-4.50D) and emmetropes (N=22, MSE±0.50D) was analyzed using color Doppler Imaging, Heidelberg retinal flowmetry and ocular blood flow analyser (OBF) respectively. Intraocular pressure, axial length (AL), systemic blood pressure, and body mass index were measured. Results. When compared to the emmetropes and low myopes, the AL was greater in high myopia (p<0.0001). High myopes showed higher central retinal artery resistance index (CRA RI) (p=0.004), higher peak systolic to end diastolic velocities ratio (CRA ratio) and lower end diastolic velocity (CRA EDv) compared to low myopes (p=0.014, p=0.037). Compared to emmetropes, high myopes showed lower OBFamplitude (OBFa) (p=0.016). The POBF correlated significantly with the systolic and diastolic blood velocities of the CRA (p=0.016, p=0.036). MSE and AL correlated negatively with OBFa (p=0.03, p=0.003), OBF volume (p=0.02, p<0.001), POBF (p=0.01, p<0.001) and positively with CRA RI (p=0.007, p=0.05). Conclusion. High myopes exhibited significantly reduced pulse amplitude and CRA blood velocity, the first of which may be due to an OBF measurement artefact or real decreased ocular blood flow pulsatility. Axial length and refractive error correlated moderately with the ocular pulse and with the resistance index of the CRA, which in turn correlated amongst themselves. It is hypothesized that the compromised pulsatile and CRA haemodynamics observed in young healthy myopes is an early feature of the decrease in ocular blood flow reported in pathological myopia. Such vascular features would increase the susceptibility for vascular and age-related eye diseases.

Quantitative assessment of the pharmacotherapy of biopolar disorder and schizophrenia

The work present in this thesis was aimed at assessing the efficacy of lithium in the acute treatment of mania and for the prophylaxis of bipolar disorder, and investigating the value of plasma haloperidol concentration for predicting response to treatment in schizophrenia. The pharmacogenetics of psychotropic drugs is critically appraised to provide insights into interindividual variability in response to pharmacotherapy, In clinical trials of acute mania, a number of measures have been used to assess the severity of illness and its response to treatment. Rating instruments need to be validated in order for a clinical study to provide reliable and meaningful estimates of treatment effects, Eight symptom-rating scales were identified and critically assessed, The Mania Rating Scale (MRS) was the most commonly used for assessing treatment response, The advantage of the MRS is that there is a relatively extensive database of studies based on it and this will no doubt ensure that it remains a gold standard for the foreseeable future. Other useful rating scales are available for measuring mania but further cross-validation and validation against clinically meaningful global changes are required. A total of 658 patients from 12 trials were included in an evaluation of the efficacy of lithium in the treatment of acute mania. Treatment periods ranged from 3 to 4 weeks. Efficacy was estimated using (i) the differences in the reduction in mania severity scores, and (ii) the ratio and difference in improvement response rates. The response rate ratio for lithium against placebo was 1.95 (95% CI 1.17 to 3.23). The mean number needed to treat was 5 (95% CI 3 to 20). Patients were twice as likely to obtain remission with lithium than with chlorpromazine (rate ratio = 1.96, 95% CI 1.02 to 3.77). The mean number needed to treat (NNT) was 4 (95% CI 3 to 9). Neither carbamazepine nor valproate was more effective than lithium. The response rate ratios were 1.01 (95% CI 0.54 to 1.88) for lithium compared to carbarnazepine and 1.22 (95% CI 0.91 to 1.64) for lithium against valproate. Haloperidol was no better than lithium on the basis of improvement based on assessment of global severity. The differences in effects between lithium and risperidone were -2.79 (95% CI -4.22 to -1.36) in favour of risperidone with respect to symptom severity improvement and -0.76 (95% CI -1.11 to -0,41) on the basis of reduction in global severity of disease. Symptom and global severity was at least as well controlIed with lithium as with verapamil. Lithium caused more side-effects than placebo and verapamil, but no more than carbamazepine or valproate. A total of 554 patients from 13 trials were included in the statistical analysis of lithium's efficacy in the prophylaxis of bipolar disorder. The mean follow-up period was 5-34 months. The relapse risk ratio for lithium versus placebo was 0.47 (95% CI 0.26 to 0.86) and the NNT was 3 (95% CI 2 to 7). The relapse risk ratio for lithium versus imipramine was 0.62 (95% CI 0.46 to 0.84) and the NNT was 4 (951% Cl 3 to 7), The combination of lithium and imipramine was no more effective than lithium alone. The risk of relapse was greater with lithium alone than with the lithium-divalproate combination. A risk difference of 0.60 (95% CI 0.21 to 0.99) and an NNT of 2 (95% CI 1 to 5) were obtained. Lithium was as effective as carbamazepine. Based on individual data concerning plasma haloperidol concentration and percent improvement in psychotic symptoms, our results suggest an acceptable concentration range of 11.20-30.30 ng/mL A minimum of 2 weeks should be allowed before evaluating therapeutic response. Monitoring of drug plasma levels seems not to be necessary unless behavioural toxicity or noncompliance is suspected. Pharmacokinetics and pharmacodynamics, which are mainly determined by genetic factors, contribute to interindividual and interethnic variations in clinical response to drugs. These variations are primarily due to differences in drug metabolism. Variability in pharmacokinetics of a number of drugs is associated with oxidation polymorphism. Debrisoquine/sparteine hydroxylase (CYP2D6) and the S-mephenytoin hydroxylase (CYP2C19) are polymorphic P450 enzymes with particular importance in psychopharmacotherapy. The enzymes are responsible for the metabolism of many commonly used antipsychotic and antidepressant drugs. The incidence of poor metabolisers of debrisoquine and S-mephenytoin varies widely among populations. Ethnic variations in polymorphic isoenzymes may, at least in part, explain ethnic differences in response to pharmacotherapy of antipsychotics and antidepressant drugs.

Equisummability Theorems for Laguerre Series

Here we prove results about Riesz summability of classical Laguerre series, locally uniformly or on the Lebesgue set of the function f such that (∫(1 + x)^(mp) |f(x)|^p dx )^(1/p) < ∞, for some p and m satisfying 1 ≤ p ≤ ∞, −∞ < m < ∞.

Analytic Renormings of C(K) Spaces

The aim of our present note is to show the strength of the existence of an equivalent analytic renorming of a Banach space, even compared to C∞-Fréchet smooth renormings. It was Haydon who first showed in [8] that C(K) spaces for K countable admit an equivalent C∞-Fréchet smooth norm. Later, in [7] and [9] he introduced a large clams of tree-like (uncountable) compacts K for which C(K) admits an equivalent C∞-Fréchet smooth norm. Recently, it was shown in [3] that C(K) spaces for K countable admit an equivalent analytic norm. Our Theorem 1 shows that in the class of C(K) spaces this result is the best possible.

A Note on Preserved Smoothness

* Supported by NSERC (Canada)

Representable Banach Spaces and Uniformly Gateaux-Smooth Norms

It is proved that a representable non-separable Banach space does not admit uniformly Gâteaux-smooth norms. This is true in particular for C(K) spaces where K is a separable non-metrizable Rosenthal compact space.

Sharp Bounds on the Number of Resonances for Symmertic Systems II. Non-Compactly Supported Perturbations

We extend the results in [5] to non-compactly supported perturbations for a class of symmetric first order systems.