Uma nova heurística para o problema de escalonamento de motoristas

O problema de escalonamento de motoristas (PEM) consiste em atribuir escalas de serviço a motoristas durante um período de planejamento, de modo a satisfazer restrições operacionais e trabalhistas, e a atingir objetivos importantes. Este problema tem sido estudado há muitos anos. Este trabalho apresenta um método heurístico que cria escalas atendendo restrições e objetivos difíceis de serem considerados em modelos de Programação Inteira. Para a heurística proposta, o PEM é dividido em cinco subproblemas, que são resolvidos em três estágios. Estes estágios são realizados de forma iterativa até que se obtenha um conjunto de boas escalas. Testes computacionais têm sido conduzidos para pequenas instâncias de um problema real de uma empresa de transporte interurbano no Brasil. Comparações dos resultados obtidos são feitas levando-se em conta o processo manual de escalonamento presentemente usado nesta empresa, assim como outros estudos referentes a escalonamento de tripulações de companhias aéreas

Autonomic thermoregulatory dysfunction in neurofibromatosis type 1 Disfunção autonômica termorregulatória na neurofibromatose do tipo 1

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder, caused by mutations in a single gene (OMIM #162200, neurofibromin, 17 q11.2) affecting the development-maintenance-repair of neural and cutaneous tissues. Neurofibromatosis type 1 is the most common human monogenetic disease (1:3000, affecting nearly 80,000 Brazilian people) and it exhibits marked phenotype expression variability and an unpredictable course 5 , and both features are related to life expectancy, and quality of life. Possible mechanisms involving NF1-reduced muscle strength and aerobic capacity could be neurological abnormalities related to the neurofibromin deficiency, such as poorer motor coordination/activation, as well as lower levels of daily physical activities and motivation for exercising. Both neural disorder and reduced aerobic capacity could adversely affect thermoregulatory capacity, leading to decreased exercise performance in hot environments and heat intolerance with higher risk for heat-related injuries 6 . Despite increases in environmental temperature and/or exercise body metabolism, human internal temperature must be maintained within a small physiological range through heat dissipation, to prevent tissue ABSTRACT Objective: Neurofibromatosis type 1 (NF1) causes neural and cutaneous disorders and reduced exercise capacity. Exercise/heat exposure increasing internal temperature must be compensated by eccrine sweat function and warmed skin vasodilation. We suspected NF1 could adversely affect eccrine sweat function and/or vascular thermoregulatory responses (VTR). Methods: The eccrine sweat function and VTR of 25 NF1 volunteers (14 males, 11 females; 16-57 years old) were compared with 23 non-NF1 controls matched by sex, age, height and weight (CG). Sweating was induced by 1) pilocarpine 1% iontophoresis (PILO); and 2) by passive heating (HEAT) via the lower third of the legs being immersed in 42°C water for one hour. Previously established eccrine sweat function and VTR protocols were used. Results: The NF1 group showed: a) lower sweat rate than the CG group during PILO; b) a smaller diastolic pressure decrease; and c) higher tympanic temperatures than controls during HEAT (p < 0.05). Conclusion: Reduced sweating and vascular thermoregulatory responses suggest autonomic dysfunction in NF1 individuals. Keywords: neurofibromatosis 1; sweating; primary dysautonomias; body temperature regulation. RESUMO Objetivo: Neurofibromatose do tipo 1 (NF1) causa problemas neurais e cutâneos e diminuição da capacidade física. O aumento da temperatura interna durante exercício e exposição ao calor precisa ser compensada pela função sudorípara écrina (FSE) e aquecimento cutâneo por vasodilatação (RVT). Suspeitou-se clinicamente que a NF1 poderia prejudicar a FSE e a RVT. Métodos: A FSE e RVT de 25 voluntários com NF1 (14 homens, 11 mulheres; 16-57 anos) e de 23 sem-NF1, emparelhados por sexo, idade, estatura e peso corporal, foram medidas com protocolos validados anteriormente. A sudorese foi induzida por iontoforese com pilocarpina (PILO) e aquecimento passivo por imersão das pernas em água a 42°C durante uma hora (HEAT). Resultados: O grupo NF1 apresentou menor taxa de sudorese na situação PILO, menor redução da pressão diastólica e maior temperatura timpânica na situação HEAT (p < 0.05). Conclusão: As respostas sudorípara e vascular reduzidas sugerem disfunção autonômica nas pessoas com NF1. Palavras-chave: neurofibromatose 1; sudorese; disautonomia primária; regulação da temperatura corporal

The Liver Plays a Major Role in Clearance and Destruction of Blood Trypomastigotes in Trypanosoma cruzi Chronically Infected Mice

Intravenous challenge with Trypanosoma cruzi can be used to investigate the process and consequences of blood parasite clearance in experimental Chagas disease. One hour after intravenous challenge of chronically infected mice with 5×106 trypomastigotes, the liver constituted a major site of parasite accumulation, as revealed by PCR. Intact parasites and/or parasite remnants were visualized at this time point scattered in the liver parenchyma. Moreover, at this time, many of liver-cleared parasites were viable, as estimated by the frequency of positive cultures, which considerably diminished after 48 h. Following clearance, the number of infiltrating cells in the hepatic tissue notably increased: initially (at 24 h) as diffuse infiltrates affecting the whole parenchyma, and at 48 h, in the form of large focal infiltrates in both the parenchyma and perivascular spaces. Phenotypic characterization of liver-infiltrating cells 24 h after challenge revealed an increase in Mac1+, CD8+ and CD4+ cells, followed by natural killer (NK) cells. As evidence that liver-infiltrating CD4+ and CD8+ cells were activated, increased frequencies of CD69+CD8+, CD69+CD4+ and CD25+CD122+CD4+ cells were observed at 24 and 48 h after challenge, and of CD25−CD122+CD4+ cells at 48 h. The major role of CD4+ cells in liver protection was suggested by data showing a very high frequency of interferon (IFN)-γ-producing CD4+ cells 24 h after challenge. In contrast, liver CD8+ cells produced little IFN-γ, even though they showed an enhanced potential for secreting this cytokine, as revealed by in vitro T cell receptor (TCR) stimulation. Confirming the effectiveness of the liver immune response in blood parasite control during the chronic phase of infection, no live parasites were detected in this organ 7 days after challenge