Computational Analysis of Intelligent Agents: Social and Strategic Settings

The central motif of this work is prediction and optimization in presence of multiple interacting intelligent agents. We use the phrase `intelligent agents' to imply in some sense, a `bounded rationality', the exact meaning of which varies depending on the setting. Our agents may not be `rational' in the classical game theoretic sense, in that they don't always optimize a global objective. Rather, they rely on heuristics, as is natural for human agents or even software agents operating in the real-world. Within this broad framework we study the problem of influence maximization in social networks where behavior of agents is myopic, but complication stems from the structure of interaction networks. In this setting, we generalize two well-known models and give new algorithms and hardness results for our models. Then we move on to models where the agents reason strategically but are faced with considerable uncertainty. For such games, we give a new solution concept and analyze a real-world game using out techniques. Finally, the richest model we consider is that of Network Cournot Competition which deals with strategic resource allocation in hypergraphs, where agents reason strategically and their interaction is specified indirectly via player's utility functions. For this model, we give the first equilibrium computability results. In all of the above problems, we assume that payoffs for the agents are known. However, for real-world games, getting the payoffs can be quite challenging. To this end, we also study the inverse problem of inferring payoffs, given game history. We propose and evaluate a data analytic framework and we show that it is fast and performant.

Revêtement intelligent à base des silices mésoporeuses fonctionnalisées pour le relargage stimulé d’agents antimicrobiens

Les biofilms bactériens sont composés d’organismes unicellulaires vivants au sein d’une matrice protectrice, formée de macromolécules naturelles. Des biofilms non désirés peuvent avoir un certain nombre de conséquences néfastes, par exemple la diminution du transfert de chaleur dans les échangeurs de chaleurs, l’obstruction de membranes poreuses, la contamination des surfaces coques de navires, etc. Par ailleurs, les bactéries pathogènes qui prolifèrent dans un biofilm posent également un danger pour la santé s’ils croissent sur des surfaces médicales synthétiques comme des implants biomédicaux, cathéters ou des lentilles de vue. De plus, la croissance sur le tissu naturel par certaines souches des bactéries peut être fatale, comme Pseudomonas aeruginosa dans les poumons. Cependant, la présence de biofilms reste difficile à traiter, car les bactéries sont protégées par une matrice extracellulaire. Pour tenter de remédier à ces problèmes, nous proposons de développer une surface antisalissure (antifouling) qui libère sur demande des agents antimicrobiens. La proximité et la disposition du système de relargage placé sous le biofilm, assureront une utilisation plus efficace des molécules antimicrobiennes et minimiseront les effets secondaires de ces dernières. Pour ce faire, nous envisageons l’utilisation d’une couche de particules de silice mésoporeuses comme agents de livraison d’agents antimicrobiens. Les nanoparticules de silice mésoporeuses (MSNs) ont démontré un fort potentiel pour la livraison ciblée d’agents thérapeutiques et bioactifs. Leur utilisation en nano médecine découle de leurs propriétés de porosité intéressantes, de la taille et de la forme ajustable de ces particules, de la chimie de leur surface et leur biocompatibilité. Ces propriétés offrent une flexibilité pour diverses applications. De plus, il est possible de les charger avec différentes molécules ou biomolécules (de tailles variées, allant de l’ibuprofène à l’ARN) et d’exercer un contrôle précis des paramètres d’adsorption et des cinétiques de relargage (désorption). Mots Clés : biofilms, nanoparticules de silice mésoporeuses, microfluidique, surface antisalissure.

Evaluation Of The Mutagenicity And Antimutagenicity Of Ziziphus Joazeiro Mart. Bark In The Micronucleus Assay.

The aim of this study was to evaluate the mutagenicity (clastogenicity/aneugenicity) of a glycolic extract of Ziziphus joazeiro bark (GEZJ) by the micronucleus assay in mice bone marrow. Antimutagenic activity was also assessed using treatments associated with GEZJ and doxorubicin (DXR). Mice were evaluated 24-48 h after exposure to positive (N-nitroso-N-ethylurea, NEU - 50 mg.kg(-1) and DXR - 5 mg.kg(-1)) and negative (150 mM NaCl) controls, as well as treatment with GEZJ (0.5-2 g.kg(-1)), GEZJ (2 g.kg(-1)) + NEU and GEZJ (2 g.kg(-1)) + DXR. There were no significant differences in the frequencies of micronucleated polychromatic erythrocytes in mice treated with GEJZ and GEJZ + DXR compared to the negative controls, indicating that GEZJ was not mutagenic. Analysis of the polychromatic:normochromatic erythrocyte ratio revealed significant differences in the responses to doses of 0.5 g.kg(-1) and 1-2 g.kg(-1) and the positive control (NEU). These results indicated no systemic toxicity and moderate toxicity at lower and higher doses of GEZJ. The lack of mutagenicity and systemic toxicity in the antimutagenic assays, especially for treatment with GEZJ + DXR, suggested that phytochemical compounds in Z. joazeiro bark attenuated DXR-induced mutagenicity and the moderate systemic toxicity of a high dose of Z. joazeiro bark (2 g.kg(-1)). Further studies on the genotoxicity of Z. joazeiro extracts are necessary to establish the possible health risk in humans and to determine the potential as a chemopreventive agent for therapeutic use.

Deregulation Of Adipokines Related To Target Organ Damage On Resistant Hypertension.

Resistant hypertension (RHTN) includes patients with controlled blood pressure (BP) (CRHTN) and uncontrolled BP (UCRHTN). In fact, RHTN patients are more likely to have target organ damage (TOD), and resistin, leptin and adiponectin may affect BP control in these subjects. We assessed the relationship between adipokines levels and arterial stiffness, left ventricular hypertrophy (LVH) and microalbuminuria (MA). This cross-sectional study included CRHTN (n=51) and UCRHTN (n=38) patients for evaluating body mass index, ambulatory blood pressure monitoring, plasma adiponectin, leptin and resistin concentrations, pulse wave velocity (PWV), MA and echocardiography. Leptin and resistin levels were higher in UCRHTN, whereas adiponectin levels were lower in this same subgroup. Similarly, arterial stiffness, LVH and MA were higher in UCRHTN subgroup. Adiponectin levels negatively correlated with PWV (r=-0.42, P<0.01), and MA (r=-0.48, P<0.01) only in UCRHTN. Leptin was positively correlated with PWV (r=0.37, P=0.02) in UCRHTN subgroup, whereas resistin was not correlated with TOD in both subgroups. Adiponectin is associated with arterial stiffness and renal injury in UCRHTN patients, whereas leptin is associated with arterial stiffness in the same subgroup. Taken together, our results showed that those adipokines may contribute to vascular and renal damage in UCRHTN patients.

Óxido nítrico: propriedades e potenciais usos terapêuticos

Nitric oxide ( NO) is a substance that acts as a second-messenger and is associated with a number of important physiological functions such as regulation of the vascular tonus, immune modulation and neurotransmission. As a physiological mediator, alteration of its concentration level may cause pathophysiological disfunctions such as hypertension, septic shock and impotence. Possible therapeutic approaches are being developed to control NO levels in vivo. We review herein the main physical and chemical properties of NO, its biological functions and available chemical interventions to reduce and increment its physiological concentration levels. Recent developments in the field are also highlighted.

Avaliação citométrica dos adipócitos localizados no tecido subcutâneo da parede anterior do abdome após infiltração percutânea de CO2

OBJETIVO: Avaliar os efeitos da infiltração de dióxido de carbono em adipócitos presentes na parede abdominal. MÉTODOS: Quinze voluntárias foram submetidas a sessões de infusão de CO2 durante três semanas consecutivas (duas sessões por semana com intervalos de dois a três dias entre cada sessão). O volume de gás carbônico infundido por sessão, em pontos previamente demarcados, foi sempre calculado com base na superfície da área a ser tratada, com volume infundido fixo de 250 mL/100cm² de superfície tratada. Os pontos de infiltração foram demarcados respeitando-se o limite eqüidistante 2cm entre eles. Em cada ponto se injetou 10mL, por sessão, com fluxo de 80mL/min. Foram colhidos fragmentos de tecido celular subcutâneo da parede abdominal anterior antes e após o tratamento. O número e as alterações histomorfológicas dos adipócitos (diâmetro médio, perímetro, comprimento, largura e número de adipócitos por campos de observação) foram mensurados por citometria computadorizada. Os resultados foram analisados com o teste t de Student pareado, adotando-se nível de significância de 5% (p<0,05). RESULTADOS: Encontrou-se redução significativa no número de adipócitos da parede abdominal e na área, diâmetro, perímetro, comprimento e largura após o uso da hipercapnia (p=0,0001). CONCLUSÃO: A infiltração percutânea de CO2 reduz a população e modifica a morfologia dos adipócitos presentes na parede abdominal anterior.

Um enfoque sanitário sobre a demanda judicial de medicamentos

No Brasil, apesar dos avanços da assistência farmacêutica, permanecem falhas na garantia do acesso dos cidadãos aos medicamentos pelo Estado. Nos últimos anos, vem crescendo a reivindicação de medicamentos por parte do cidadão via sistema judiciário. Os objetos dessas solicitações são tanto os medicamentos em falta na rede pública como aqueles ainda não incorporados pelo Sistema Único de Saúde. Este fenômeno pode ser analisado sob diferentes perspectivas, inclusive a sanitária, entendida aqui como os desfechos sobre a saúde dos indivíduos que demandam estes medicamentos. O presente texto busca discutir as principais características das demandas judiciais frente aos seguintes aspectos: o uso racional de medicamentos, o uso de evidências científicas para a indicação terapêutica proposta e o quanto as demandas se justificam diante do conceito de acesso adotado pelo campo da assistência farmacêutica. Ponderações podem ser feitas no sentido de minimizar os riscos à saúde dos demandantes de medicamentos por via judicial, sobretudo quando o objeto da ação são medicamentos não pertencentes às listas de fornecimento público, ou com uso off label, ou desprovidos de registro no país. Considera-se que o Judiciário, a partir do fornecimento de medicamentos, busca garantir a saúde dos demandantes, e assim a dignidade da pessoa humana. Cabe ressaltar que este objetivo só será atingido quando a garantia da saúde estiver associada aos aspectos que certificam a segurança do paciente, inclusive no uso de medicamentos.

Estudo randômico da correção cirúrgica do prolapso uterino através de tela sintética de polipropileno tipo I comparando histerectomia versus preservação uterina

OBJETIVO: Comparar os resultados anatômicos pós-operatórios de pacientes portadoras de prolapso uterino tratadas utilizando tela de polipropileno para correção dos defeitos do assoalho pélvico, comparando histerectomia vaginal com a preservação do útero. MÉTODO: Estudo randomizado com 31 mulheres portadoras de prolapso uterino estádio III ou IV (POP-Q) divididas em dois grupos: Grupo HV- 15 mulheres submetidas à histerectomia vaginal e reconstrução da anatomia do assoalho pélvico com tela de polipropileno tipo I (Nazca R-Promedon) e Grupo HP- 16 mulheres mulheres submetidas à reconstrução da anatomia do assoalho pélvico com tela de polipropileno tipo I (Nazca R-Promedon) preservando o útero. Raça, urgência miccional, constipação intestinal, dor sacral, sangramento e tempo de operação foram os parâmetros analisados. RESULTADOS: O tempo de seguimento médio foi de nove meses. Não se observou diferença entre os grupos nas complicações funcionais. O tempo cirúrgico foi 120 minutos para grupo HV versus 58.9 minutos para grupo HP ( p < 0.001 ) e o volume de perda sanguínea intraoperatória foi 120 mL no grupo HV versus 20 mL para grupo HP ( p < 0.001*). A taxa de sucesso objetivo foi 86.67% para grupo HV e 75% para grupo HP (p = 0,667). A taxa de erosão de tela foi 20% (3/15) de extrusão no grupo HV versus 18,75% (3/16) no grupo HP (p = 1,000). CONCLUSÃO: A correção cirúrgica do assoalho pélvico com telas nas portadoras de prolapso uterino apresentaram similaridade quer sendo ela feita com histeropexia quer com histerectomia. Contudo, o tempo cirúrgico e o volume da perda sanguínea foram significantemente maiores no grupo com histerectromia (HV). Operações vaginais com telas são procedimentos efetivos para a correção do prolapso.

An 18-Week, Prospective, Randomized, Double-Blind, Multicenter Study of Amlodipine/Ramipril Combination Versus Amlodipine Monotherapy in the Treatment of Hypertension: The Assessment of Combination Therapy of Amlodipine/Ramipril (ATAR) Study

Background: A combination of antihypertensive agents of different drug classes in a fixed-dose combination (FDC) may offer advantages in terms of efficacy, tolerability, and treatment compliance. Combination of a calcium channel blocker with an angiotensin-converting enzyme inhibitor may act synergistically to reduce blood pressure (BP). Objective: The aim of this study was to compare the efficacy and tolerability of an amlodipine/ramipril FDC with those of amlodipine monotherapy. Methods: This 18-week, prospective, randomized, double-blind study was conducted at 8 centers across Brazil. Patients with stage 1 or 2 essential hypertension were enrolled. After a 2-week placebo run-in phase, patients received amlodipine/ramipril 2.5/2.5 mg or amlodipine 2.5 mg, after which the doses were titrated, based on BP, to 515 then 10/10 mg (amlodipme/ramipril) and 5 then 10 mg (amiodipine). The primary end point was BP measured in the intent-to-treat (ITT) population. Hematology and serum biochemistry were assessed at baseline and study end. Tolerability was assessed using patient interview, laboratory analysis, and physical examination, including measurement of ankle circumference to assess peripheral edema. Results: A total of 222 patients completed the study (age range, 40-79 years; FDC group, 117 patients [mean dose, 7.60/7.60 mg]; monotherapy, 105 patients [mean dose, 7.97 mg]). The mean (SD) changes in systolic BP (SBP) and diastolic BP (DBP), as measured using 24-hour ambulatory blood pressure monitoring (ABPM) and in the physician`s office, were significantly greater with combination therapy than monotherapy, with the exception of office DBP (ABPM, -20.76 [1.25] vs -15.80 [1.18] mm Hg and -11.71 [0.78] vs -8.61 [0.74] mm Hg, respectively [both, P = 0.004]; office, -27.51 [1.40] vs -22.84 [1.33] min Hg [P = 0.012] and -16.41 [0.79] vs -14.64 [0.75] mm Hg [P = NS], respectively). In the ITT analysis, the mean changes in ambulatory, but not office-based, BP were statistically significant (ABPM: SBP, -20.21 [1.14] vs -15.31 [1.12] mm Hg and DBP, -11.61 [0.72] vs -8.42 [0.70] mm Hg, respectively [both, P = 0.002]; office: SBP, -26.60 [1.34] vs -22.97 [1.30] mm Hg and DBP, -16.48 [0.78] vs -14.48 [0.75] mm Hg [both, P = NS]). Twenty-nine patients (22.1%) treated with combination therapy and 41 patients (30.6%) treated with monotherapy experienced >= 1 adverse event considered possibly related to study drug. The combmation-therapy group had lower prevalence of edema (7.6% vs 18.7%; P = 0.011) and a similar prevalence of dry cough (3.8% vs 0.8%; P = NS). No clinically significant changes in laboratory values were found in either group. Conclusions: In this population of patients with essential hypertension, the amlodipine/ramipril FDC was associated with significantly reduced ambulatory and office-measured BP compared with amlodipine monotherapy, with the exception of office DBP. Both treatments were well tolerated. (Clin Ther. 2008;30: 1618-1628) (C) 2008 Excerpta Medica Inc.

Intralesional pentoxifylline as an adjuvant treatment for perioral post-burn hypertrophic scars

Pentoxifylline (PTF), a methylxanthine derivative, has therapeutic use as an antifibrotic agent. In vitro, PTF inhibits the production of collagen and reduces the proliferation of fibroblasts in hypertrophic scars. This study aimed to evaluate changes in the elasticity of hypertrophic scars in the peribuccal area in burned patients, who presented with mouth-opening limitation. Eighteen patients were divided into two groups. The case group (n = 10) was treated with PTF 1 mg ml(-1), while in the control group (n = 8) no treatment was performed. Measurements of mouth opening (lip-to-lip and tooth-to-tooth distances in mm) were taken, before and after five therapeutic sessions with pentoxifylline with weekly intervals. The variations of these measures (Delta%) were calculated and submitted to statistical analyses. There was a significant improvement in the opening of the mouth, in vermilion distance (V = 3.20 mm) as much as the dental distance (DD = 4.19 mm) in the treated group, than in the control group. It was noted that pentoxifylline increases the elasticity of hypertrophic scars in the perioral area. (C) 2009 Elsevier Ltd and ISBI. All rights reserved.

Zipping up transcription factors: Rational design of anti-Jun and anti-Fos peptides

Various members of the bZip and bHLH-Zip families of eukaryotic transcription factors, including Jun, Fos, and Myc, have been identified as oncoproteins; mutation or deregulated expression of these proteins leads to certain types of cancer. These proteins can only bind to their cognate DNA enhancer sites following homodimerization, or heterodimerization with another family member, via their leucine zipper domain. Thus, a novel anticancer strategy would be to inhibit dimerization of these proteins, thereby blocking their DNA binding and transactivation functions. In this paper we show that it is possible to rationally design leucine zipper peptides that bind with high affinity to the leucine zipper dimerization domains of c-Jun and c-Fos, thus preventing the formation of functional c-Jun homodimers and c-Jun:c-Fos heterodimers; we refer to such peptides as superzippers (SZs). In vivo, c-Jun:SZ and c-Fos:SZ heterodimers should be nonfunctional as they lack one of the two basic domains that are essential for DNA binding. While the transport of a peptidic agent into cells often poses a severe obstacle to its therapeutic use, we show that a 46-residue leucine zipper peptide can be transported into HeLa cells by coupling it to a 17-residue carrier peptide from the Antennapedia homeodomain, thus paving the way for detailed studies of the therapeutic potential of superzipper peptides.

A 65-year experience treating acne, including 26 years with oral isotretinoin

This special article is based on the contents of a lecture given by Sampaio and was written together with Bagatin. it is a summary of the authors` experience treating various forms of acne before and after the introduction of oral isotretinoin, which revolutionized the management of the disease. Nowadays, this drug is considered the unique option to obtain a prolonged remission or cure of acne due to its action in all etiopathogenic factors involved in the disease. Therefore it should be prescribed in accordance to current recommendations, as well as for difficult cases, including those showing tendency to scars or serious psychological and social repercussions. Other topical and/or systemic therapeutic modalities should be considered in the initial approach and for mild and moderate cases.

Action of aromatase inhibitor for treatment of uterine leiomyoma in perimenopausal patients

Objective: To assess the effect of the aromatase inhibitor on patients with leiomyoma in the reproductive stage regarding reduction of uterine volume and control of symptoms. Design: Clinical study. Setting: Academic clinical practice. Patient(s): Twenty patients, over 35 years of age, with symptomatic uterine leiomyoma. Intervention(s): Anastrozol, 1 mg/day for 12 weeks. Main Outcome Measure(s): Measurement of uterine volume, assessment of symptoms related to uterine leiomyoma, serum assay of follicle stimulating hormone (FSH), and estradiol. Results: Average reduction of uterine volume of 9.32%, attaining up to 32%, and reduction of symptoms of uterine leiomyoma (menstrual volume, duration of menstruation, and dysmenorrhea). No significant change in serum levels of FSH and estradiol during use of the medication were observed. Conclusion(S): Anastrozol proved to be effective in reducing the volume of the uterus-leiomyoma structure, leading to the control of symptoms connected with the disorder without changes in serum FSH and estradiol. (Fertil Steril (R) 2009;91:240-3. (c) 2009 by American Society for Reproductive Medicine.)

Low-Intensity Pulsed Ultrasound Accelerates Healing in Rat Calcaneus Tendon Injuries

STUDY DESIGN: Controlled laboratory study. OBJECTIVE: To evaluate the effect of low-intensity therapeutic ultrasound on the murine calcaneus tendon healing process. BACKGROUND: Therapeutic ultrasound promotes formation and maturation of scar tissue. METHODS: Calcaneus tendon tenotomy and tenorrhaphy was performed on 28 Wistar rats. After the procedure, the animals were randomly divided into 2 groups. The animals in the experimental group received a 5-minute ultrasound application, once a day, at a frequency of 1 MHz, a spatial average temporal average intensity of 0.1 W/cm(2), and a spatial average intensity of 0.52 W/cm(2) at a 16-Hz frequency pulse mode (duty cycle, 20%). Data for the injured side were normalized in relation to the data from the contralateral healthy calcaneus tendon (relative values). The animals in the control group received sham treatment. After a 28-day treatment period, the animals were sacrificed and their tendons surgically removed and subjected to mechanical stress testing. The parameters analyzed were cross-sectional area (mm(2)), ultimate load (N), tensile strength (MPa), and energy absorption (mJ). RESULTS: A significant difference between groups was found for the relative values of ultimate load and tensile strength. The mean +/- SD ultimate load of the control group was -3.5% +/- 32.2% compared to 33.3% +/- 26.8% for the experimental group (P = .005). The mean tensile strength of the control group was -47.7% +/- 19.5% compared to -28.1% +/- 24.1% for the experimental group (P = .019). No significant difference was found in cross-sectional area and energy absorption. CONCLUSION: Low-intensity pulsed ultrasound produced by a conventional therapeutic ultrasound unit can positively influence the calcaneus tendon healing process in rats. J Ort hop Sports Phys Ther 2011;41(7):526-531, Epub 2 February 2011. doi:10.2519/jospt.2011.3468

Analysis of Craniofacial and Extremity Growth in Patients with Growth Hormone Deficiency during Growth Hormone Therapy

Background/Aims: There are many controversies regarding side effects on craniofacial and extremity growth due to growth hormone ( GH) treatment. Our aim was to estimate GH action on craniofacial development and extremity growth in GH-deficient patients. Methods: Twenty patients with GH deficiency with a chronological age ranging from 4.6 to 24.3 years (bone age from 1.5 to 13 years) were divided in 2 groups: group 1 (n = 6), naive to GH treatment, and group 2 (n = 14), ongoing GH treatment for 2-11 years. GH doses (0.1 -0.15 U/kg/day) were adjusted to maintain insulin-like growth factor 1 and insulin-like growth factor binding protein 3 levels within the normal range. Anthropometric measurements, cephalometric analyses and facial photographs to verify profile and harmony were performed annually for at least 3 years. Results: Two patients with a disharmonious profile due to mandibular growth attained harmony, and none of them developed facial disharmony. Increased hand or foot size (>P97) was observed in 2 female patients and in 4 patients (1 female), respectively, both not correlated with GH treatment duration and increased levels of insulin-like growth factor 1. Conclusions: GH treatment with standard doses in GH-deficient patients can improve the facial profile in retrognathic patients and does not lead to facial disharmony although extremity growth, mainly involving the feet, can occur. Copyright (C) 2009 S. Karger AG, Basel