Loss of p16 expression is associated with histological features of melanoma invasion

While mutations of CDKN2A are associated with melanoma predisposition, the precise role of its gene product p16 in the development of sporadic melanoma is less clearly understood. We sought to determine the prevalence of p16 expression using immunohistochemical analysis in a population-based sample of melanoma tumours, and also to identify histological, phenotypic and environmental factors associated with the presence or absence of p16 expression. We conducted face-to-face interviews with 108 patients newly diagnosed with melanoma to ascertain their history of sun exposure, and recorded various phenotypic parameters. Paraffin sections of tumours from these patients were stained with an anti-p16 monoclonal antibody following antigen retrieval. Overall, 52 (48%) tumours expressed p16; nodular melanomas had significantly lower levels of p16 immunoreactivity than superficial spreading melanomas (P = 0.015). While no association was found between p16 expression and host phenotype, loss of p16 staining was associated with thicker lesions (p = 0.084) and a high mitotic index (P = 0.013). Taken together, these findings are consistent with loss of p16 being a late event in the progression of sporadic primary melanomas, being associated with tumours of a more aggressive nature. (C) 2002 Lippincott Williams Wilkins.

Crystallization of the FAD-independent acetolactate synthase of Klebsiella pneumoniae

Leucine and valine are formed in a common pathway from pyruvate in which the first intermediate is 2-acetolactate. In some bacteria, this compound also has a catabolic fate as the starting point for the butanediol fermentation. The enzyme (EC 4.1.3.18) that forms 2-acetolactate is known as either acetohydroxyacid synthase (AHAS) or acetolactate synthase (ALS), with the latter name preferred for the catabolic enzyme. A significant difference between AHAS and ALS is that the former requires FAD for catalytic activity, although the reason for this requirement is not well understood. Both enzymes require the cofactor thiamine diphosphate. Here, the crystallization and preliminary X-ray diffraction analysis of the Klebsiella pneumoniae ALS is reported. Data to 2.6 Angstrom resolution have been collected at 100 K using a rotating-anode generator and an R-AXIS IV++ detector. Crystals have unit-cell parameters a = 137.4, b = 143.9, c = 134.4 Angstrom, alpha = 90, beta = 108.4, gamma = 90degrees and belong to space group C2. Preliminary analysis indicates that there are four monomers located in each asymmetric unit.

Chebyshev real wave packet propagation: H+O-2 (J=0) state-to-state reactive scattering calculations

In this paper we explore the relative performance of two recently developed wave packet methodologies for reactive scattering, namely the real wave packet Chebyshev domain propagation of Gray and Balint-Kurti [J. Chem. Phys. 108, 950 (1998)] and the Lanczos subspace wave packet approach of Smith [J. Chem. Phys. 116, 2354 (2002); Chem. Phys. Lett. 336, 149 (2001)]. In the former method, a modified Schrodinger equation is employed to propagate the real part of the wave packet via the well-known Chebyshev iteration. While the time-dependent wave packet from the modified Schrodinger equation is different from that obtained using the standard Schrodinger equation, time-to-energy Fourier transformation yields wave functions which differ only trivially by normalization. In the Lanczos subspace approach the linear system of equations defining the action of the Green operator may be solved via either time-dependent or time-independent methods, both of which are extremely efficient due to the simple tridiagonal structure of the Hamiltonian in the Lanczos representation. The two different wave packet methods are applied to three dimensional reactive scattering of H+O-2 (total J=0). State-to-state reaction probabilities, product state distributions, as well as initial-state-resolved cumulative reaction probabilities are examined. (C) 2002 American Institute of Physics.

Making decisions about treatment for localized prostate cancer

Objective To describe the decision-making processes used by men diagnosed with localized prostate cancer who were considering treatment. Patients and methods Men newly diagnosed with localized prostate cancer from outpatient urology clinics and urologist's private practices were approached before treatment. Their decision-making processes and information-seeking behaviour was assessed; demographic information was also obtained. Results Of 119 men approached, 108 (90%) were interviewed; 91% reported non-systematic decision processes, with deferral to the doctor, positive and negative recollections of others' cancer experiences, and the pre-existing belief that surgery is a better cancer treatment being most common. For systematic information processing the mean (SD, range) number of items considered was 4.19 (2.28, 0-11), with 57% of men considering four or fewer treatment/medical aspects of prostate cancer. Men most commonly considered cancer stage (59%), urinary incontinence (55%) and impotence (51%) after surgery, and low overall mortality (45%). Uncertainty about probabilities for cure was reported by 43% of men and fear of cancer spread by 37%. Men also described uncertainty about the probabilities of side-effects (27%), decisional uncertainty (25%) and anticipated decisional regret (18%). Overall, 73% of men sought information about prostate cancer from external sources, most commonly the Internet, followed by family and friends. Conclusions In general, men did not use information about medical treatments comprehensively or systematically when making treatment decisions, and their processing of medical information was biased by their previous beliefs about cancer and health. These findings have implications for the provision of informational and decisional support to men considering prostate cancer treatment.

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.

Using crop simulation to generate genotype by environment interaction effects for sorghum in water-limited environments

Multi-environment trials (METs) used to evaluate breeding lines vary in the number of years that they sample. We used a cropping systems model to simulate the target population of environments (TPE) for 6 locations over 108 years for 54 'near-isolines' of sorghum in north-eastern Australia. For a single reference genotype, each of 547 trials was clustered into 1 of 3 'drought environment types' (DETs) based on a seasonal water stress index. Within sequential METs of 2 years duration, the frequencies of these drought patterns often differed substantially from those derived for the entire TPE. This was reflected in variation in the mean yield of the reference genotype. For the TPE and for 2-year METs, restricted maximum likelihood methods were used to estimate components of genotypic and genotype by environment variance. These also varied substantially, although not in direct correlation with frequency of occurrence of different DETs over a 2-year period. Combined analysis over different numbers of seasons demonstrated the expected improvement in the correlation between MET estimates of genotype performance and the overall genotype averages as the number of seasons in the MET was increased.

Protocolos assistenciais como estrat??gia de ades??o ??s melhores pr??ticas cl??nicas e otimiza????o de recursos

Este trabalho descreve a metodologia para desenvolvimento, implementa????o e avalia????o dos protocolos assistenciais no Hospital de Cl??nicas de Porto Alegre (HCPA), concebida para duas fases: fase I: elabora????o dos protocolos e implementa????o em material impresso e fase II: adapta????o para sistema informatizado e concep????o de um software para acompanhamento dos protocolos assistenciais. Na avalia????o foram considerados indicadores cl??nico-assistenciais espec??ficos para cada patologia e percep????o dos m??dicos residentes desta ferramenta

O processo decis??rio da reforma tribut??ria e da previd??ncia social: per??odo de 1994 a 1998

An??lise da reforma constitucional no governo Fernando Henrique Cardoso a partir dos estudos de caso da reforma tribut??ria e da previd??ncia social, compreendendo tamb??m uma reconstitui????o do processo decis??rio de pol??ticas nestas ??reas desde a era Collor.

Do her??ico ao cotidiano: li????es aprendidas na condu????o de projetos horizontais

Este Caderno traz o relat??rio elaborado pela Mesa-Redonda de Pesquisa A????o sobre a Gest??o de Iniciativas Horizontais, do Centro Canadense para o Desenvolvimentoda Gest??o do Canad??, que objetiva avaliar iniciativas e pesquisas realizadas,identificar li????es e oferecer orienta????es pr??ticas a gerentes sobre efic??ciaem gest??o horizontal

Relat??rio de gest??o 2004

Apresenta a necessidade de vincular a capacita????o de servidores p??blicos aos objetivos estrat??gicos do governo e das institui????es, bem como formar quadros para carreiras do servi??o p??blico, a ENAP estabeleceu como diretrizes ser escola com padr??o de qualidade, espa??o de reflex??o e debate e centro de refer??ncia em gest??o das pol??ticas p??blicas. Desta forma, s??o apresentadas as atividades realizadas pela Escola no ano de 2004, observando a Norma de Execu????o no 004, de 22 de dezembro de 2004, da Controladoria-Geral da Uni??o, Secretaria Federal de Controle Interno

Relat??rio de Gest??o 2011

Relat??rio de Gest??o do exerc??cio de 2011 apresentado aos ??rg??os de controle interno e externo como presta????o de contas anual a que esta Unidade est?? obrigada nos termos do art. 70 da Constitui????o Federal, elaborado de acordo com as disposi????es da IN TCU n?? 63/2010, da DN TCU n?? 108/2010, da Portaria TCU n?? 123/2011 e das orienta????es do ??rg??o de controle interno (Portaria CGU n?? 2546/2010)

Texto para discuss??o 31: custos no servi??o p??blico

O texto analisa o gasto p??blico e aspectos hist??ricos do seu desenvolvimento no Brasil, defendendo sua apura????o para o desenvolvimento de uma administra????o p??blica mais efic??z.

Disciplina 3.5: compras, contratos e licita????es

A disciplina teve como principais conte??dos: contrata????es no setor p??blico. Lei 8.666. Contrata????o por dispensa e inexigibilidade de licita????o. Preg??o Eletr??nico. Contrato Administrativo: regime jur??dico, gest??o, altera????es, fiscaliza????o, san????es. Riscos quanto ?? motiva????o do gasto, ?? compatibilidade do pre??o praticado, ao recebimento (liquida????o da despesa) e ?? destina????o para fins de interesse p??blico. Julgados do Tribunal de Contas da Uni??o sobre o tema

M??dulo 3: divulga????o do instrumento convocat??rio, habilita????o dos licitantes, propostas, encerramento: cautelas e boas pr??ticas: curso sele????o de fornecedores de TI (SFTI)

Esse documento trata de: habilita????o; processamento da licita????o; qualifica????o t??cnica (art. 30 da Lei 8.666/93; dilig??ncias; recursos administrativos; posicionamento da ??rea de TI; coer??ncia Estrita com o Edital; modelo de sele????o de Fornecedores; crit??rios de julgamento; capacidade t??cnico-operacional; capacidade t??cnico-profissional; parecer t??cnico para subsidiar o pregoeiro ou a comiss??o; an??lise de pre??o; amostra ou prot??tipo; adjudica????o e homologa????o

E agora, Shakti? : como formular uma nova lei ambiental em uma sociedade politicamente dividida?

O estudo de caso analisa o dilema enfrentado pela presidente de uma rep??blica fict??cia na elabora????o do Novo C??digo Florestal de seu pa??s. O enfoque est?? centrado na tarefa ??rdua de conciliar desenvolvimento econ??mico e prote????o ambiental numa ??nica legisla????o. O debate se d?? em torno da trama pol??tica que envolve a tomada de decis??o em momentos de crise e na necessidade de se discutir coletivamente temas sens??veis para a sociedade. Como conciliar direito ao desenvolvimento com prote????o ambiental num pa??s marcado por lutas? Como decidir em meio ?? press??o pol??tica de grupos divergentes? O estudo de caso centra os debates em torno da gest??o do meio ambiente num contexto de expans??o econ??mica baseada no agroneg??cio. O material did??tico pode ser utilizado em disciplinas relacionadas a Direito Ambiental, Direito Internacional P??blico, Direitos Humanos e Administra????o P??blica.