Optimal and sub-optimal control in Dengue epidemics

This work concerns the application of the optimal control theory to Dengue epidemics. The dynamics of this insect-borne disease is modelled as a set of non-linear ordinary differential equations including the effect of educational campaigns organized to motivate the population to break the reproduction cycle of the mosquitoes by avoiding the accumulation of still water in open-air recipients. The cost functional is such that it reflects a compromise between actual financial spending (in insecticides and educational campaigns) and the population health (which can be objectively measured in terms of, for instance, treatment costs and loss of productivity). The optimal control problem is solved numerically using a multiple shooting method. However, the optimal control policy is difficult to implement by the health authorities because it is not practical to adjust the investment rate continuously in time. Therefore, a suboptimal control policy is computed assuming, as the admissible set, only those controls which are piecewise constant. The performance achieved by the optimal control and the sub-optimal control policies are compared with the cases of control using only insecticides when Breteau Index is greater or equal to 5 and the case of no-control. The results show that the sub-optimal policy yields a substantial reduction in the cost, in terms of the proposed functional, and is only slightly inferior to the optimal control policy. Copyright (C) 2001 John Wiley & Sons, Ltd.

Usefulness of Mycobacterium tuberculosis molecular typing in a tuberculosis low-endemic agro-industrial setting of Brazil

To highlight the transmission and major phylogenetic clades of Mycobacterium tuberculosis, a retrospective study was carried out at two health facilities in a small agro-industrial area in São Paulo, Brazil, that has a low tuberculosis incidence rate. IS6110-RFLP and spoligotyping were performed on the isolates, with the former revealing that 31.3% (35/112) of strains were clustered. Epidemiological links were found in 16 of the 35 clustered patients and were associated with transmission among patients living in public housing. Spoligotyping grouped 62.8% of the strains. The T genetic family predominated among the isolates. Of interest is that five strains had a pattern characteristic of African or Asian origin (ST535), and two others were of the rare localized type ST1888 (BRA, VEN). In addition, three new types-1889, 1890, and 1891-were identified. Spoligotyping showed that some ST may be circulating to or from Brazil, and RFLP revealed ongoing transmission in inadequately ventilated public-housing buildings. This may point to a failure in tuberculosis control policy.

Overall-Mouth Disinfection by Photodynamic Therapy Using Curcumin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Experience generalization for multi-agent reinforcement learning

On-line learning methods have been applied successfully in multi-agent systems to achieve coordination among agents. Learning in multi-agent systems implies in a non-stationary scenario perceived by the agents, since the behavior of other agents may change as they simultaneously learn how to improve their actions. Non-stationary scenarios can be modeled as Markov Games, which can be solved using the Minimax-Q algorithm a combination of Q-learning (a Reinforcement Learning (RL) algorithm which directly learns an optimal control policy) and the Minimax algorithm. However, finding optimal control policies using any RL algorithm (Q-learning and Minimax-Q included) can be very time consuming. Trying to improve the learning time of Q-learning, we considered the QS-algorithm. in which a single experience can update more than a single action value by using a spreading function. In this paper, we contribute a Minimax-QS algorithm which combines the Minimax-Q algorithm and the QS-algorithm. We conduct a series of empirical evaluation of the algorithm in a simplified simulator of the soccer domain. We show that even using a very simple domain-dependent spreading function, the performance of the learning algorithm can be improved.

Análise dos processos e instrumentos de ordenação do território: comparação entre Brasil e Portugal

Pós-graduação em Geografia - IGCE

Aminophylline affects glycemia control and increases anaerobic glycolysis in horses during incremental exercise

A study was conducted on the effects of acute administration of aminophylline on physiological variables in purebred Arabian horses submitted to incremental exercise test. Twelve horses were submitted to two physical tests separated by a 10-day interval in a crossover study. These horses were divided into two groups: control (C, n = 12) and aminophylline (AM, n = 12). The drug at 10 mg/kg body weight or saline was given intravenously, 30 minutes before the incremental exercise test. The treadmill exercise test consisted of an initial warmup followed by gradually increasing physical exigency. Blood samples were assayed for lactic acid, glucose, and insulin. Maximal lactic acidemia was greater (P = .0238) in the AM group. Both V-2 and V-4 (velocities at which lactate concentrations were 2 and 4 mmol/ L, respectively) were reduced in the AM group by 15.85% (P = .0402) and 17.76% (P = .0 109), respectively. At rest as well as at 4 minutes, insulinemia was greater in the AM group (P = .0417 and .0393), Glycemia group at times 8 was statistically lower in the Al (P = .0138) and 10 minutes (P = .0432). Use of ammophylline in horses during incremental exercise does not seem to be beneficial, because this drug has a tendency to cause hypoglycemia and to increase dependence on anaerobic glucose metabolism.

Fiscal policy contradiction: a perspective on Brazil and Mexico

The aim of this paper is to discuss the quality of fiscal policy in Brazil and Mexico and investigate whether fiscal policy influence is favorable to reduce the unemployment rate. Public spending, which has a positive effect on the level of employment when results in additional aggregate demand, may cause a negative effect on employment, if its financing depends on persistent high interest rates. Brazil and Mexico have engaged in a long effort to control public spending and to reduce the public deficit to zero. Does this policy bring a positive result to the economic activity no matter how actual public deficit has been financed? We select variables related to public budget as public sector borrowing requirements, taxes, public debt and others to form a data base. The fiscal institutional arrangement and the data allow us to evaluate the fiscal policy as a whole and to discuss the importance of credibility and reputation of the government.

Rheological, Mechanical and Adhesive Properties of Surfactant-Containing Systems Designed as a Potential Platform for Topical Drug Delivery

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chitosan-pectin multiparticulate systems associated with enteric polymers for colonic drug delivery

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Controlled Drug Release from Ureasil-Polyether Hybrid Materials

Flexible, transparent, and insoluble urea-cross-linked polyether-siloxane hybrids presenting a tunable drug delivery pattern were prepared using the sol-gel method from PEO (poly(ethylene oxide)) and PPO (poly(propylene oxide)) functionalized at both chain ends with triethoxysilane. Different polyether chain lengths were used to control the urea/siloxane (named ureasil) node density, flexibility, and swellability of the hybrid network. We herein demonstrate that the drug release from swellable hydrophilic ureasil-PEO hybrids can be sustained for some days, whereas that from the unswellable ureasil-PPO hybrids can be sustained for some weeks. This outstanding feature conjugated with the biomedically safe formulation of the ureasil cross-linked polyether-siloxane hybrid widens their scope of application to include the domain of soft and implantable drug delivery devices.

Controlled transscleral drug delivery formulations to the eye: establishing new concepts and paradigms in ocular anti-inflammatory therapeutics and antibacterial prophylaxis

Importance of the field: The use of topical agents poses unique and challenging hurdles for drug delivery. Topical steroids effectively control ocular inflammation, but are associated with the well-recognized dilemma of patient compliance. Although administration of topical antimicrobials as prophylaxis is acceptable among ophthalmologists, this common practice has no sound evidence base Developing a new antimicrobial agent or delivery strategy with enhanced penetration by considering the anatomical and physiological constraints exerted by the barriers of the eye is not a commonly perceived strategy. Exploiting the permeability of the sclera, subconjunctival routes may offer a promising alternative for enhanced drug delivery and tissue targeting.Area covered in this review: Ocular drug delivery strategies were reviewed for ocular inflammation and infections clinically adopted for newer class of antimicrobials, which use a multipronged approach to limit risks of endophthalmitis.What the reader will gain: The analysis substantiates a new transscleral drug delivery therapeutic approach for cataract surgery.Take home message: A new anti-inflammatory and anti-infective paradigm that frees the patient from the nuisance of topical therapeutics is introduced, opening a large investigative avenue for future improved therapies.

Natural rubber latex used as drug delivery system in guided bone regeneration (GBR)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Short and long period optimization of drug doses in the treatment of AIDS

Técnicas de otimização numérica são úteis na solução de problemas de determinação da melhor entrada para sistemas descritos por modelos matemáticos e cujos objetivos podem ser expressos de uma maneira quantitativa. Este trabalho aborda o problema de otimizar as dosagens dos medicamentos no tratamento da AIDS em termos de um balanço entre a resposta terapêutica e os efeitos colaterais. Um modelo matemático para descrever a dinâmica do vírus HIV e células CD4 é utilizado para calcular a dosagem ótima do medicamento no tratamento a curto prazo de pacientes com AIDS por um método de otimização direta utilizando uma função custo do tipo Bolza. Os parâmetros do modelo foram ajustados com dados reais obtidos da literatura. Com o objetivo de simplificar os procedimentos numéricos, a lei de controle foi expressa em termos de uma expansão em séries que, após truncamento, permite obter controles sub-ótimos. Quando os pacientes atingem um estado clínico satisfatório, a técnica do Regulador Linear Quadrático (RLQ) é utilizada para determinar a dosagem permanente de longo período para os medicamentos. As dosagens calculadas utilizando a técnica RLQ , tendem a ser menores do que a equivalente terapia de dose constante em termos do expressivo aumento na contagem das células T+ CD4 e da redução da densidade de vírus livre durante um intervalo fixo de tempo.

Interaction between paraventricular nucleus and septal area in the control of physiological responses induced by angiotensin II

We determined the effects of losartan (40 nmol) and PD 123319 (40 nmol) (both non-peptides and selective antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar¹, Ala8] angiotensin II (ANG II) (40 nmol) (a non-selective peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on the water and salt appetite, diuresis and natriuresis and mean arterial pressure (MAP) induced by administration of 10 nmol of ANG II into the medial septal area (MSA) of male Holtzman rats weighing 250-300 g. The volume of drug solution injected was 0.5 µl over a period of 10-15 s. The responses were measured over a period of 120 min. ANG II alone injected into the MSA induced an increase in all the above parameters (8.1 ± 1.2, 1.8 ± 0.3, and 17.1 ± 1.0 ml, 217 ± 25 µEq/120 min, and 24 ± 4 mmHg, respectively, N = 10-12) compared with vehicle-treated rats (1.4 ± 0.2, 0.6 ± 0.1, and 9.3 ± 0.5 ml, 47 ± 5 µEq/120 min, and 4.1 ± 0.8 mmHg, respectively, N = 10-14). Pretreatment with losartan and [Sar¹, Ala8] ANG II completely abolished the water and sodium intake, and the pressor increase (0.5 ± 0.2, 1.1 ± 0.2, 0.5 ± 0.2, and 0.8 ± 0.2 ml, and 1.2 ± 3.9, 31 ± 4.6 mmHg, respectively, N = 9-12), whereas losartan blunted the urinary and sodium excretion induced by ANG II (13.9 ± 1.0 ml and 187 ± 10 µEq/120 min, respectively, N = 9). Pretreatment with PD 123319 and [Sar¹, Ala8] ANG II blocked the urinary and sodium excretion (10.7 ± 0.8, 9.8 ± 0.7 ml, and 67 ± 13 and 57 ± 17 µEq/120 min, respectively, N = 9), whereas pretreatment with PD 123319 partially blocked the water and sodium intake, and the MAP induced by ANG II administration (2.3 ± 0.3, 1.1 ± 0.1 ml, and 12 ± 3 mmHg, respectively, N = 9-10). These results suggest the angiotensinergic effect of the MSA on the AT1 and AT2 receptors of the PVN in terms of water and sodium homeostasis and MAP modulation.

REACTIVE OXYGEN GENERATION BY AZOMETHINE-H - A NEW ANTIMALARIAL DRUG

Superoxide radical (O-2(-)) is a free radical that may be involved in various toxic processes. Cu-Zn superoxide dismutase catalyzes the dismutation of the superoxide free radical and protects cells from oxidative damage. A rat bioassay validated for the identification of the toxic effects of azomethine H revealed increased serum activities of amylase, alanine transaminase, and alkaline phosphatase. The lipoperoxide and bilirubin concentrations were also increased in animals that received azomethine H (1 g/kg) from ascorbic or hydrochloric acid solutions. Azomethine H increased Cu-Zn superoxide dismutase activity. This elevation of Cu-Zn superoxide dismutase activity was highest on the 7th day and was at levels comparable with those of control rats from day 60 onwards. Superoxide is an important intermediate in the action and toxicity of azomethine H.