Comparison of two population pharmacokinetic programs, NONMEM and P-PHARM, for tacrolimus

Objectives: To compare the population modelling programs NONMEM and P-PHARM during investigation of the pharmacokinetics of tacrolimus in paediatric liver-transplant recipients. Methods: Population pharmacokinetic analysis was performed using NONMEM and P-PHARM on retrospective data from 35 paediatric liver-transplant patients receiving tacrolimus therapy. The same data were presented to both programs. Maximum likelihood estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F). Covariates screened for influence on these parameters were weight, age, gender, post-operative day, days of tacrolimus therapy, transplant type, biliary reconstructive procedure, liver function tests, creatinine clearance, haematocrit, corticosteroid dose, and potential interacting drugs. Results: A satisfactory model was developed in both programs with a single categorical covariate - transplant type - providing stable parameter estimates and small, normally distributed (weighted) residuals. In NONMEM, the continuous covariates - age and liver function tests - improved modelling further. Mean parameter estimates were CL/F (whole liver) = 16.3 1/h, CL/F (cut-down liver) = 8.5 1/h and V/F = 565 1 in NONMEM, and CL/F = 8.3 1/h and V/F = 155 1 in P-PHARM. Individual Bayesian parameter estimates were CL/F (whole liver) = 17.9 +/- 8.8 1/h, CL/F (cutdown liver) = 11.6 +/- 18.8 1/h and V/F = 712 792 1 in NONMEM, and CL/F (whole liver) = 12.8 +/- 3.5 1/h, CL/F (cut-down liver) = 8.2 +/- 3.4 1/h and V/F = 221 1641 in P-PHARM. Marked interindividual kinetic variability (38-108%) and residual random error (approximately 3 ng/ml) were observed. P-PHARM was more user friendly and readily provided informative graphical presentation of results. NONMEM allowed a wider choice of errors for statistical modelling and coped better with complex covariate data sets. Conclusion: Results from parametric modelling programs can vary due to different algorithms employed to estimate parameters, alternative methods of covariate analysis and variations and limitations in the software itself.

Antagonism by NKP608 of substance P-induced plasma protein exudation in a novel preparation of perfused trachea in rats and guinea-pigs in vivo

Objective: To examine whether NKP608, a novel 1-benzoyl-2-benzyl-4-aminopiperidine NK1 receptor antagonist, inhibits substance P (SP)-induced airway plasma protein exudation in vivo. Material: Anaesthetised English shorthair guinea-pigs and Wistar rats. Treatment: Tachykinin peptides were applied topically onto the trachea and antagonists administered intravenously. Methods: Tracheal segments isolated in situ were perfused with saline and plasma-derived protein assayed in the perfusate. Results: SP (1 muM) caused plasma protein exudation, which was abolished by an NK1 antagonist (RP 67580, 1.75 mumol/kg) but unaffected by an NK2 antagonist (SR 48968, 1.75 mumol/kg) indicating the response is NK1-receptor-mediated. This was confirmed with a response to an NK1 agonist ([Sar(9), Met(O-2)(11)]-SP, 1 muM) but none to an NK2 agonist ([betaAla(8)]-neurokinin A(4-10), 1 muM). NKP608 inhibited SP responses with estimated ID50 values (mumol/kg) of 0.0044 (guinea-pigs) and 0.19 (rats). Conclusions: NKP608 is an antagonist in vivo of NK1 receptor-induced tracheal plasma protein exudation and is more potent in guinea-pigs than rats.

Binder treatment and lubricant system for aluminium P/M

Organic binders are used in premixes for powder metallurgy applications to prevent dusting and segregation. This is a particular problem for aluminium powder metallurgy because the dust is a potential safety hazard. The binder must also burn out completely at low temperatures in an inert environment and not react with the metal powders. It is demonstrated that cellulose acetate, polyvinyl acetate and polyvinyl alcohol are effective dedusting agents but they react with the metal powders during sintering and decrease the sintered density. Paraffin wan is an effect dedusting agent that provided die wall lubricity, does not interfere with sintering and increases tensile strength and ductility.

Influence of planting date, method of handling and seed size on supersweet sweet corn seed quality

A supersweet sweet corn hybrid, Pacific H5, was planted at weekly intervals (P-1 to P-5) in spring in South-Eastern Queensland. All plantings were harvested at the same time resulting in immature seed for the last planting (P-5). The seed was handled by three methods: manual harvest and processing (M-1), manual harvest and mechanical processing (M-2) and mechanical harvest and processing (M-3), and later graded into three sizes (small, medium and large). After eight months storage at 12-14degreesC, seed was maintained at 30degreesC with bimonthly monitoring of germination for fourteen months and seed damage at the end of this period. Seed quality was greatest for M-1 and was reduced by mechanical processing but not by mechanical harvesting. Large and medium seed had higher germination due to greater storage reserves but also more seed damage during mechanical processing. Immature seed from premature harvest (P-5) had poor quality especially when processed mechanically and reinforced the need for harvested seed to be physiologically mature.

Thermodynamic non-ideality as an alternative source of the effect of sucrose on the thrombin-catalyzed hydrolysis of peptide p-nitroanalide substrates

The inhibitory effect of sucrose on the kinetics of thrombin-catalyzed hydrolysis of the chromogenic substrate S-2238 (D-phenylalanyl-pipecolyl-arginoyl-p-nitroanilide) is re-examined as a possible consequence of thermodynamic non-ideality-an inhibition originally attributed to the increased viscosity of reaction mixtures. However, those published results may also be rationalized in terms of the suppression of a substrate-induced isomerization of thrombin to a slightly more expanded (or more asymmetric) transition state prior to the irreversible kinetic steps that lead to substrate hydrolysis. This reinterpretation of the kinetic results solely in terms of molecular crowding does not signify the lack of an effect of viscosity on any reaction step(s) subject to diffusion control. Instead, it highlights the need for development of analytical procedures that can accommodate the concomitant operation of thermodynamic non-ideality and viscosity effects.

Numerical study of hydrogenic effective mass theory for an impurity P donor in Si in the presence of an electric field and interfaces

In this paper we examine the effects of varying several experimental parameters in the Kane quantum computer architecture: A-gate voltage, the qubit depth below the silicon oxide barrier, and the back gate depth to explore how these variables affect the electron density of the donor electron. In particular, we calculate the resonance frequency of the donor nuclei as a function of these parameters. To do this we calculated the donor electron wave function variationally using an effective-mass Hamiltonian approach, using a basis of deformed hydrogenic orbitals. This approach was then extended to include the electric-field Hamiltonian and the silicon host geometry. We found that the phosphorous donor electron wave function was very sensitive to all the experimental variables studied in our work, and thus to optimize the operation of these devices it is necessary to control all parameters varied in this paper.

Description of Paeon asymboli n. sp. (Copepoda : Sphyriidae), parasitic on Asymbolus spp. (catsharks) and a new host record for P-australis Kabata, 1993.

Paeon asymboli n. sp. ( Copepoda: Sphyriidae) is described and illustrated from two female specimens taken from the gills of a grey spotted catshark Asymbolus analis ( Ogilby) and an orange spotted catshark A. rubiginosus ( Last, Gomon & Gledhill) ( Scyliorhinidae) from off southeastern Queensland, Australia. The key features for identification are: a pear- shaped trunk, longer than it is wide, along with a cephalothorax characterised by two large ventral papillae, projecting laterally and supporting a number of secondary lobes; a single mid- line, subconical papilla located antero- dorsal to the ventral papillae; an anterior surface bearing two prominent stalked papillae; and an absence of posterolateral lobular processes. P. australis Kabata, 1993 is recorded for the first time from the eastern shovelnose ray Aptychotrema rostrata ( Shaw & Nodder) ( Rhinobatidae).

Boletim eletr??nico de bibliografias especializadas: inova????o na gest??o p??blica

O 4?? Boletim Eletr??nico de Bibliografias Especializadas destaca o tema ???Inova????o na Gest??o P??blica???, com indica????es de livros e artigos de revistas pertencentes ao acervo da Biblioteca. O intuito ?? divulgar obras que auxiliem servidores p??blicos na transforma????o de processos de trabalho para melhor atender ao cidad??o.

Boletim eletr??nico de bibliografias especializadas:acesso ?? informa????o p??blica

A Lei de Acesso ?? Informa????o (n??12.527/2011) entra em vigor hoje, dia 16 de maio, e traz importantes mudan??as para a administra????o p??blica. A nova legisla????o proporciona, ao cidad??o brasileiro, o acesso amplo ??s informa????es e a documentos p??blicos sob a guarda do Estado. A partir dessa data, todo cidad??o poder??, a qualquer momento, solicitar informa????es diversas, sem necessidade de motiva????o para seu uso, garantindo, assim, o exerc??cio de seu direito constitucional ao acesso ?? informa????o p??blica. A Lei estabelece que o acesso seja a regra e o sigilo, a exce????o. Diante desse cen??rio, o 5?? Boletim Eletr??nico de Bibliografias Especializadas destaca o tema ???Acesso ?? informa????o???, com indica????es de publica????es pertencentes ao acervo da Biblioteca Graciliano Ramos/ENAP. O intuito ?? divulgar obras que auxiliem servidores p??blicos na compreens??o dos princ??pios da nova Lei e na mudan??a da cultura do sigilo, ainda presente na gest??o da informa????o p??blica.

Boletim eletr??nico de bibliografias especializadas: pol??ticas p??blicas em direitos humanos

Os direitos humanos s??o os direitos essenciais a todos os seres humanos, sem que haja discrimina????o por ra??a, cor, g??nero, idioma, nacionalidade ou por qualquer outro motivo. Eles podem ser civis ou pol??ticos, como o direito ?? vida, ?? igualdade perante a lei e ?? liberdade de express??o. Podem tamb??m ser econ??micos, sociais e culturais, como o direito ao trabalho e ?? educa????o e coletivos, como o direito ao desenvolvimento. As Pol??ticas P??blicas em Direitos Humanos ?? tema deste boletim bibliogr??fico, o qual traz publica????es que mostram que estas n??o devem ser apenas programas governamentais, mas um instrumento de participa????o da sociedade civil na delimita????o do espa??o p??blico.

Boletim eletr??nico de bibliografias especializadas: gest??o de pessoas no servi??o p??blico

Diante de uma sociedade mais din??mica e complexa, a ado????o de uma pol??tica permanente de desenvolvimento do capital humano ?? o caminho para a supera????o dos desafios no setor p??blico. Dessa forma ?? poss??vel ofertar servi??os de excel??ncia aos cidad??os, bem como promover a inova????o e a melhoria na qualidade da gest??o p??blica. O presente Boletim apresenta uma sele????o de publica????es, dentre a vasta quantidade de obras sobre o tema existentes no acervo da Biblioteca Graciliano Ramos, que retratam os obst??culos existentes para o desenvolvimento de pessoas no servi??o p??blico, com o objetivo de convergir as necessidades e anseios dos quadros funcionais ??s necessidades organizacionais

Boletim eletr??nico de bibliografias especializadas: qualifica????o e valoriza????o dos servidores p??blicos

O dia do servidor p??blico ?? comemorado em 28 de outubro desde 1937, quando da cria????o do Conselho Federal do Servi??o P??blico Civil. Desde ent??o, muito se conquistou em rela????o ao reconhecimento desse profissional. Hoje, os servidores t??m consci??ncia da import??ncia de sua atua????o para o desenvolvimento econ??mico e social do pa??s. O incentivo aos servidores p??blicos, por meio de a????es voltadas ?? forma????o e ?? capacita????o permanentes, ?? fundamental para motiv??-los a prestar servi??os de excel??ncia aos cidad??os. Com base na pol??tica vigente e em homenagem ao dia do servidor, a Biblioteca Graciliano Ramos traz como tema de seu 9?? Boletim Eletr??nico de Bibliografias Especializadas uma sele????o de publica????es, pertencentes ao seu acervo, que abordam a quest??o da qualifica????o e da valoriza????o dos servidores p??blicos

Portal do software p??blico brasileiro

O Portal do Software P??blico Brasileiro consolida-se como uma iniciativa que conseguiu criar um ambiente comum para compartilhar solu????es de software no setor p??blico, racionalizar a gest??o dos recursos de inform??tica, reaproveitar as solu????es de software existentes para diminuir custos e atividades redundantes, estabelecer parcerias e a????es cooperadas, refor??ar a pol??tica p??blica de estimular o uso de software livre e definir uma forma de licenciamento de software que sustente o compartilhamento de solu????es entre os ??rg??os do setor p??blico de acordo com as prerrogativas legais brasileiras e a Constitui????o Federal. Esta iniciativa trouxe como inova????o o compartilhamento de ???software p??blico???, que oficializou um novo modelo de licenciamento e de gest??o das solu????es desenvolvidas na administra????o p??blica, estabelecendo parceria entre diversos ??rg??os, institui????es, empresas e cidad??os, e hoje conta com mais de 100 mil participantes