Action Of Different Agents Research Articles

Hybrid dynamical systems logic and its refinements

Hybrid dynamical systems describe the mixed discrete dynamics and continuous dynamics of cyber-physical systems such as aircraft, cars, trains, and robots. To justify correctness properties of the safety-critical control algorithms for their physical models, differential dynamic logic (▪) provides deductive specification and verification techniques implemented in the theorem prover ▪. The logic ▪ is useful for proving, e.g., that all runs of a hybrid dynamical system α satisfy safety property φ (i.e., ▪), or that there is a run of the hybrid dynamical system α ultimately reaching the desired goal φ (i.e., ▪). Logical combinations of ▪'s operators naturally represent safety, liveness, stability and other properties. Variations of ▪ serve additional purposes. Differential refinement logic (▪) adds an operator α≤β expressing that hybrid system α refines hybrid system β, which is useful, e.g., for relating concrete system implementations α to their abstract verification models β. Just like ▪, ▪ is a logic closed under all operators, which opens up systematic ways of simultaneously relating systems and their properties, of reducing system properties to system relations or, vice versa, reducing system relations to system properties. A second variant of ▪, differential game logic (▪), adds the ability of referring to winning strategies of players in hybrid games, which is useful for establishing correctness properties where the actions of different agents may interfere either because they literally compete with one another or because they may interact accidentally. In the theorem prover ▪, ▪ and its variations have been used for verifying ground robot obstacle avoidance, the Federal Aviation Administration's Next-Generation Airborne Collision Avoidance System ACAS X, and the Federal Railroad Administration's train control model.

Is all the UNESCO´s Qhapaq Ñan really Inca? Problems with the incorporation of sections and sites from San Juan (Argentina)

The nomination and acceptance of the Qhapaq Ñan as World Heritage took more than a decade of work in the six countries involved. In Argentina, a centralized coordination system in charge of articulating the proposals of the provinces that were part of the national program was implemented. Some people expressed certain inconveniences in the program’s development, mainly related to the participation of native communities. Furthermore, the presentation approved by UNESCO shows some shortcomings associated with the identification of some of the proposed elements. In this sense, and in order to provide relevant information to better understand the Argentinean nomination process and its outcome, this article shows the divergences between the Inca Road system known in San Juan and the one accepted in the project, the nomination of a section and associated sites without the corresponding evidence of their Inca character and a failed previous proposal to incorporate historical sites to the project. Also, to help explain this situation, some aspects related to the actions of different agents and the possible incidence of political power are discussed.

Governança adaptativa: desafio para regiões metropolitanas brasileiras

Abstract The purpose of this article is to present a theoretical discussion about the institutional dimension of the concept of adaptive governance. We discuss examples of this institutional dimension based on an analysis of the limits to the implementation of adaptive governance in Brazilian metropolises, based on: 1) the financial resources available to the environmental management of municipalities belonging to metropolitan regions; 2) the creation of an institutional arrangement for climate governance in the municipality of Rio de Janeiro. Despite the incremental aspect, the analyzed data indicate the low fiscal relevance of the environmental issue, as well as difficulties in implementing governance arrangements that succeed in providing transversal planning capacity, mechanisms for the integrated action of different agents, and incentives to an enhanced participatory dynamics in the formulation and implementation of climate policies.

Modeling of Poly(Ethylene Terephthalate) Homogeneous Glycolysis Kinetics.

Polymer composites with various recycled poly(ethylene terephthalate)-based (PET-based) polyester matrices (poly(ethylene terephthalate), copolyesters, and unsaturated polyester resins), similar in properties to the primary ones, can be obtained based on PET glycolysis products after purification. PET glycolysis allows one to obtain bis(2-hydroxyethyl) terephthalate and oligo(ethylene terephthalates) with various molecular weights. A kinetic model of poly(ethylene terephthalate) homogeneous glycolysis under the combined or separate action of oligo(ethylene terephthalates), bis(2-hydroxyethyl) terephthalate, and ethylene glycol is proposed. The model takes into account the interaction of bound, terminal, and free ethylene glycol molecules in the PET feedstock and the glycolysis agent. Experimental data were obtained on the molecular weight distribution of poly(ethylene terephthalate) glycolysis products and the content of bis(2-hydroxyethyl) terephthalate monomer in them to verify the model. Homogeneous glycolysis of PET was carried out at atmospheric pressure in dimethyl sulfoxide (DMSO) and N-methyl-2-pyrrolidone (NMP) solvents with catalyst based on antimony trioxide (Sb2O3) under the action of different agents: ethylene glycol at temperatures of 165 and 180 °C; bis(2-hydroxyethyl) terephthalate at 250 °C; and oligoethylene terephthalate with polycondensation degree 3 at 250 °C. Homogeneous step-by-step glycolysis under the successive action of the oligo(ethylene terephthalate) trimer, bis(2-hydroxyethyl) terephthalate, and ethylene glycol at temperatures of 250, 220, and 190 °C, respectively, was also studied. The composition of products was confirmed using FTIR spectroscopy. Molecular weight characteristics were determined using gel permeation chromatography (GPC), the content of bis(2-hydroxyethyl) terephthalate was determined via extraction with water at 60 °C. The developed kinetic model was found to be in agreement with the experimental data and it could be used further to predict the optimal conditions for homogeneous PET glycolysis and to obtain polymer-based composite materials with desired properties.

STUDY REGARDING THE INFLUENCE OF CORROSIVE AGENTS ON THE SURFACE OF METALLIC MATERIAL LIKE STEEL

Corrosion is a process that involves the action of different agents on material surfaces. Corrosive agents in corrosion field can be ambient, saline and microbiological mediums. These agents can influence the mechanical properties of metallic material like steel. The aim of this research is to present the mechanic properties of sheet steel submitted at the action of corrosive agents. The metallic samples were analyzed in order to determinate the resistance at corrosion by stress-strain curves, deformation limit curves and (Atomic Force microscopy) AFM images. Relative results are obtained in the case of saline medium corrosion, meaning that the saline medium corrosion influences the metallic sample, in proportion to the degree of salinity. Also, the AFM images and topographies of metallic surface confirm this conclusion.

A Systematic Review of the Effectiveness of Virtual Reality-Based Interventions on Pain and Range of Joint Movement Associated with Burn Injuries.

Background: Burns are mild or severe lesions produced in living tissue, due to the action of different agents. This pathology is considered the third cause of accidental death in the world by the World Health Organization. Among the most disabling sequelae in these patients, pain and range of motion have the greatest impact. A recommended tool to complement the treatment or management of the symptoms associated with burns is virtual reality. Objective: The objective of this study was to analyse the effectiveness of virtual-reality therapy for pain relief and the improvement of the range of joint movement in patients who have suffered burns. Methodology: This study is a systematic review conducted following the PRISMA statements. An electronic literature search was performed in the following databases: PubMed, Cochrane, Dialnet, Scopus and Science Direct. The inclusion criteria were: participants with burns in any part of the body, interventions with virtual reality with or without complementary treatment, studies in both Spanish and English, and outcome measures of pain and range of motion. Results: Finally, 10 studies were included in the review. The sample consisted of one pilot study, three randomized controlled clinical trials, one prospective randomized controlled clinical trial, one control group and treatment group trial, one interventional clinical trial and three comparative studies. The most commonly used assessment tools for pain were the graphic rating scale (GRS) and for range of motion the goniometer. The use of virtual-reality games significantly reduced pain scores during physiotherapy and occupational therapy treatments as well as in nursing care. The range of motion improved significantly during virtual-reality exercises performed during a physiotherapy treatment in 33% of studies included in this review. Conclusion: The results of the studies analysed in this systematic review suggest that the use of virtual reality for the management of pain and range of movement limitations associated with burn injuries could control these symptoms and decrease their negative consequences on the person.

Osmoprotection in Salvia hispanica L. seeds under water stress attenuators.

Salvia hispanica cultivation is recent in Brazil and occurs in the off-season, when there is lower water availability in the soil. Water deficit is one of the abiotic factors that most limit germination for compromising the sequence of metabolic events that culminate with seedling emergence. Several attenuating substances have been used to mitigate the effects resulting from this stress and give higher tolerance to the species. Thus, the objective of this study was to evaluate the action of different agents as water stress attenuators in the germination and accumulation of organic compounds in S. hispanica seedlings. The treatments consisted of pre-soaking the seeds for 4 hours in salicylic acid (1 mM.L-1), gibberellic acid (0.4 mM.L-1), distilled water and control treatment (without soaking). The seeds were germinated at osmotic potentials of 0.0, -0.1, -0.2, -0.3 and -0.4 MPa, using PEG 6000 as an osmotic agent. The variables germination percentage, germination speed index, shoot and primary root lengths, total dry mass, proline, total soluble sugars and total free amino acids were analyzed. Salicylic acid and gibberellic acid led to the best results among the attenuators tested, increasing germination, length, dry mass and biochemical components of S. hispanica seedlings under water deficit. Therefore, salicylic and gibberellic acids are efficient in mitigating water stress in S. hispanica seeds up to the potential of -0.4 MPa.

Inscribing soft rules: a study of the transnational issue field of business and human rights

This paper explores how soft rules are inscribed into corporate behavior in transnational issue fields. We study processes of inscription and the outcomes of these processes using an inductive approach to an embedded, single-case study of international guidelines complaints mechanism in the transnational field of business and human rights. Our findings three main sequential mechanisms for soft rule inscription in corporate behavior through the actions of different agents of the issue field: publicizing issue by monitoring agent, legitimating complaint by a field authority, and engagement of the targeted corporation with the monitoring agent and the field authority. Furthermore, our study of outcomes revealed that the soft rule inscription process leads to changes in corporate positioning relative to the issue and to other actors in the transnational issue field. These findings from the level of actors’ interaction contribute to knowledge on institutionalization processes at the level of the field in transnational issue fields.

De la “extinción” a las “comunidades nuevas”. Reconstitución comunitaria indígena: Paicil Antriao y Campo Maripe (Neuquén)

This paper analyzes the trajectory of two indigenous communities from Neuquen through one century, focusing on the paths followed to access and remain in their territories, as well as the highs and lows in relation to their persistence as mapuche communities. The main goal was to explain how they achieved their current state of community reconstitution, and their relationship with politics at a provincial level, specifically in the context of the development of a new political line within the Confederacion Mapuche de Neuquen at the beginning of this century. The article studied the factors that, from the genocide to the native peoples on, conditioned their possibilities of staying cohesive in a context of struggle with dominant territorialities: public policies on access to land, designed by the National State first, and then by the province, the actions of different agents in office, the mapuche political praxis and the bond they established with their supracommunal organizations. The heterogeneity of situations in the space of Neuquen led to define two cases to develop the analysis: Paicil Antriao, in the southern Andes area, and Campo Maripe, in the central eastern plateau zone.

Niche-like Ex Vivo High Throughput (NEXT) Drug Screening Platform in Acute Myeloid Leukemia

Context. Functional precision medicine is gaining momentum in AML, notably through ex vivo drug sensitivity screening (DSS) of primary patient (pt) cells (Pemovska Cancer Discov 2013, Tyner Nature 2018). The DSS landscape differs across genetic AML subgroups (Tyner Nature 2016), of which NPM1mut is the most frequent (Papaemmanuil NEJM 2016). DSS in AML has mostly been done in standard conditions, with overall viability as unique endpoint. Niche signals, which can be partly mimicked in vitro, convey drug resistance in vivo. Drugs can induce a variety of cell fates in AML. Induction of differentiation rather than killing of blasts, can result in false negative results in global viability assays. Persistence of leukemic stem cells (LSC) represents a major cause of treatment failure. GPR56 is a ubiquitous surface marker enriching for LSCs and stable upon short-term ex vivo culture (Pabst Blood 2016). Objectives. To develop an ex vivo niche-like multiparametric DSS platform for primary AML cells. To validate its clinical relevance in NPM1mut pts treated with conventional DNR-AraC chemotherapy. To discover new sensitizers to DNR-AraC chemotherapy in NPM1mut AML. Results. We designed an MFC panel to count viable blasts and measure their differentiation (CD11b/CD14/CD15) and stemness (GPR56) after exclusion of residual lymphocytes (Figure 1A). We validated GPR56 expression as stemness marker based on increased retention of GPR56+ cells in niche-like coculture combining hypoxia (O2 3%) and MSC compared to standard conditions (p<0.0001, Figure 1B) and limit dilution assays of residual GPR56+ cells at 72h of niche-like culture in 3 NPM1mut AMLs (Figure 1C). Using a limited panel of 14 drugs or combinations at fixed concentrations, our MFC readout after 72h of coculture with MSC+hypoxia revealed the distinct mode of action of different agents or combinations including the differentiation activity of ATO-ATRA, the LSC-sparring cytotoxicity of DNR-AraC and the anti-LSC- activity of VEN (Figure 1D). To further mimic in vivo conditions, we derived a MEMa-based plasma-like medium (PLM) based on targeted metabolomics (Figure 1E) and electro-chemoluminescent cytokine assays of 29 diagnostic AML bone marrow plasma samples compared to conditioned media of primary AML cells cultured in niche-like conditions (MSC, hypoxia). This instructed the design of our custom PLM with dialyzed FBS and defined low-dose (~1 ng/mL range) cytokines (CK) and amino-acid (AA) concentrations. We next investigated the contribution of MSCs, hypoxia, plasma-like AAs and CKs on blasts viability, differentiation, stemness and drug response in 3 NPM1mut AMLs exposed to fixed concentrations of 6 core AML therapies. This analysis uncovered significant interactions between these 4 niche components in dictating blast viability and stemness upon 72h ex vivo culture (Figure 1F) and revealed the distinct contribution of these niche components to drug sensitivity. RNA-seq of primary blasts cultured in niche-like, plasma-like conditions revealed marked enrichment of stemness pathways compared to ex vivo culture in standard conditions. Finally, we explored DNR-AraC (five-point serial dilution) alone or in combination with fixed, clinically relevant concentrations of 24 drugs in 49 primary AML samples (including 34 NPM1mut). Using AUCs of DNR-AraC on lymphocytes as internal control, we first validated our NEXT assay on NPM1 MRD levels in the 34 NPM1mut pts treated frontline with conventional DNR-AraC regimens (Figure 1G). Across all 49 pts, we uncovered 11 different optimal 'third-drugs', stressing the role of our NEXT assay to deploy precision medicine in daily practice. At the population level, we could nominate 3 top combinations, two of which are currently in clinical investigation (Venetoclax and Selinexor). The unpublished sensitizing effect of low dose (0.25µM) Ruxolitinib on DNR-AraC uncovered with our NEXT assay is currently being investigated in PDX models. Conclusion. We designed the NEXT assay, a multiparametric drug screening of AML viability, differentiation and stemness in niche-like culture combining hypoxia, stromal interactions and plasma-like medium. Components of the niche-like culture interact to govern leukemic viability and stemness. Our assay could predict MRD achievement in NPM1mut AML and identifies novel sensitizers to DNR-AraC in these pts. Disclosures Clappier: Amgen: Honoraria, Research Funding. Ades:Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; jazz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding; novartis: Research Funding; Celgene/BMS: Research Funding. Itzykson:Amgen: Membership on an entity's Board of Directors or advisory committees; Otsuka Pharma: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Stemline: Membership on an entity's Board of Directors or advisory committees; Oncoethix (now Merck): Research Funding; Janssen: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Daiichi Sankyo: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS (Celgene): Honoraria; Sanofi: Honoraria; Astellas: Honoraria.

Variations in lithic artefact density as a tool for better understanding Middle Palaeolithic human behaviour: The case of Nesher Ramla (Israel)

Variability in the composition of lithic assemblages stems from the combined action of different agents. In this study we used shifts in the relation between lithic artefact density and lithic technological organisation as a tool to better understand the underlying causes of lithic techno-typological variability throughout the archaeological sequence of Nesher Ramla (Israel). Nesher Ramla is a Middle Palaeolithic open-air site found in a karst sinkhole, where human occupation took place in situ. The upper part of the site's sequence (Units II-I, dated to Marine Isotope Stage 5), is characterised by sharp shifts in lithic artefact densities, concomitant with changes in the composition of the lithic assemblages. Using lithic artefact density as a proxy, we were able to partially dissect palimpsests at the site as well as isolate which components of the lithic assemblages are affected by the length of the site occupation and which are possibly the outcome of different activities performed on-site (i.e., the site function) or result from the stylistic preferences of the site inhabitants. We suggest that the role played by the site within past hunter-gatherers’ mobility systems changed from the occupation of Unit IIB-Lower, when it was possibly repeatedly used for hunting and processing animal resources, to Unit I, when it was only sporadically visited for more general purposes. Morphological changes in the karst sinkhole over time are suggested as the major causes of change in site use.

Landscape of visions: the Ekolsund manorial estate, Sweden

Parks and gardens are characterized by constant change and the need to be continuously managed and recreated. Over time, layers of history are built up, reflecting artistic and human ideals, socio-economic factors, technology and practices from different periods. Designed landscapes are archives and often have significant levels of biodiversity. One example is the Ekolsund manorial estate in Sweden, laid out in the seventeenth century in a large-scale project. Buildings, gardens and parks formed part of an overall architectural composition, where representation and display were key elements. With its audacity and grandeur, Ekolsund represents a new approach to landscape design in Sweden. The later development includes an early attempt by King Gustavus III to create landscape gardens and, during the era of capitalist owners, the planting of arboreta. Despite favourable conditions for a restoration of the seventeenth-century designed landscape, this paper argues for a holistic approach, where visions and actions of different agents - that together have shaped Ekolsund - are the foundation. Where cultural and natural values complement each other, requiring collaboration between research disciplines and the cultural heritage and nature conservation sectors.

Does patient health behaviour respond to doctor effort?

Incentive pay systems have been introduced in public sectors such as education and health care. In these sectors the output (education or health respectively) depends on the actions of different agents and it is unclear what the effects of such incentive systems are on the behaviour of untargeted agents. In this study we focus on patient health, modelled as a joint product of patient effort (through lifestyle and behaviour) and doctor effort (through diagnosis and treatment). Patient response to doctor effort is shown to be a priori ambiguous and depends on the degree of complementarity or substitution between doctor and patient effort. We build an empirical model to estimate the effect of doctors’ treatment effort on patient behaviour. To address the endogeneity of doctor effort we exploit a change in payments to doctors in the U.K. that led to incentive changes that varied by practice, depending on their prior performance levels. We use panel data on the physical activity, drinking and smoking behaviours of over 2000 cardiovascular disease patients aged over 50 in England and link these data to their primary care practice performance data. Our results indicate that primary care practices increased the proportion of patients with controlled disease from 76% to 83% in response to the payment change. Patients responded by reducing the frequency of drinking alcohol and their cigarette consumption, suggesting that patient efforts are complements to doctor effort. Understanding such complementarities has implications for assessing the design and effectiveness of pay-for-performance schemes which encourage higher doctor effort.

A thermal after-effect of UV irradiation of muscle glycogen phosphorylase b

Different test systems are used to characterize the anti-aggregation efficiency of molecular chaperone proteins and of low-molecular-weight chemical chaperones. Test systems based on aggregation of UV-irradiated protein are of special interest because they allow studying the protective action of different agents at physiological temperatures. The kinetics of UV-irradiated glycogen phosphorylase b (UV-Phb) from rabbit skeletal muscle was studied at 37°C using dynamic light scattering in a wide range of protein concentrations. It has been shown that the order of aggregation with respect to the protein is equal to unity. A conclusion has been made that the rate-limiting stage of the overall process of aggregation is heat-induced structural reorganization of a UV-Phb molecule, which contains concealed damage.

Future perspectives in melanoma research : Meeting report from the "Melanoma Bridge". Napoli, December 1st-4th 2015.

The sixth “Melanoma Bridge Meeting” took place in Naples, Italy, December 1st–4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin’s disease. Specifically, many clinical successes have been using checkpoint receptor blockade, including T cell inhibitory receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death-1 (PD-1) and its ligand PD-L1. Despite demonstrated successes, responses to immunotherapy interventions occur only in a minority of patients. Attempts are being made to improve responses to immunotherapy by developing biomarkers. Optimizing biomarkers for immunotherapy could help properly select patients for treatment and help to monitor response, progression and resistance that are critical challenges for the immuno-oncology (IO) field. Importantly, biomarkers could help to design rational combination therapies. In addition, biomarkers may help to define mechanism of action of different agents, dose selection and to sequence drug combinations. However, biomarkers and assays development to guide cancer immunotherapy is highly challenging for several reasons: (i) multiplicity of immunotherapy agents with different mechanisms of action including immunotherapies that target activating and inhibitory T cell receptors (e.g., CTLA-4, PD-1, etc.); adoptive T cell therapies that include tissue infiltrating lymphocytes (TILs), chimeric antigen receptors (CARs), and T cell receptor (TCR) modified T cells; (ii) tumor heterogeneity including changes in antigenic profiles over time and location in individual patient; and (iii) a variety of immune-suppressive mechanisms in the tumor microenvironment (TME) including T regulatory cells (Treg), myeloid derived suppressor cells (MDSC) and immunosuppressive cytokines. In addition, complex interaction of tumor-immune system further increases the level of difficulties in the process of biomarkers development and their validation for clinical use. Recent clinical trial results have highlighted the potential for combination therapies that include immunomodulating agents such as anti-PD-1 and anti-CTLA-4. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors on T cells and other approaches such as adoptive cell transfer are tested for clinical efficacy in melanoma as well. These agents are also being tested in combination with targeted therapies to improve upon shorter-term responses thus far seen with targeted therapy. Various locoregional interventions that demonstrate promising results in treatment of advanced melanoma are also integrated with immunotherapy agents and the combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for melanoma patients’ population. This meeting’s specific focus was on advances in immunotherapy and combination therapy for melanoma. The importance of understanding of melanoma genomic background for development of novel therapies and biomarkers for clinical application to predict the treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into personalized-medicine approach for treatment of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma. We also discussed the requirements for pre-analytical and analytical as well as clinical validation process as applied to biomarkers for cancer immunotherapy. The concept of the fit-for-purpose marker validation has been introduced to address the challenges and strategies for analytical and clinical validation design for specific assays.

Analysis of nanostructure of red blood cells membranes by space Fourier transform of AFM images

Atomic force microscopy (AFM) allows a researcher to obtain images of red blood cells (RBC) and their membranes. Various effects on blood lead to surface alterations of cell membranes. Such alterations are estimated by a corrugation of membrane surface. This problem is complicated for statistical analysis because the membrane is the ensemble of structures with different sizes.In the present work we used the space Fourier transform to decompose the complex AFM image of the surface into three simpler ones. The parameters of spectral windows were selected according to the natural structures of RBC membranes. This method allowed us to obtain high resolution images for the corresponding spectral windows, to establish specificity of alterations from each effect, to estimate quantitatively the membrane nanostructures at different space scales and to compare their sizes statistically after actions of different agents. The blood intoxication was modeled by adding hemin, furosemide, chlorpromazine and zinc ions into blood, in vitro.

Oncolytic Virotherapy of Glioma: What Does it Need to Make it Work?

Oncolytic virotherapy is a highly promising approach, with diverse viruses currently under development as therapeutic agents to treat malignant glioma. Although the first clinical trials did not show toxicity or serious adverse events related to intracerebral administration, overall the antitumor efficacy has fallen short of expectations. This article discusses multiple options on how to improve and maximize the effectiveness of oncolytic virus therapy in brain cancer, including strategies to enhance safety by attenuating neurovirulence via cancer-specific cell-targeting, increasing antitumor potency by transgene-arming and integrating the ability to trigger an effective antitumoral immune response, as well as developing optimized delivery routes in order to boost intratumoral viral distribution. Eventually, it will highlight the use of multipronged approaches, combining multiple modes of action of different agents.

Scaling Up Multiagent Planning: A Best-Response Approach

Multiagent planning is computationally hard in the general case due to the exponential blowup in the action space induced by concurrent action of different agents. At the same time, many scenarios require the computation of plans that are strategically meaningful for self-interested agents, in order to ensure that there would be sufficient incentives for those agents to participate in a joint plan. In this paper, we present a multiagent planning and plan improvement method that is based on conducting iterative best-response planning using standard single-agent planning algorithms. In constrained types of planning scenarios that correspond to congestion games, this is guaranteed to converge to a plan that is a Nash equilibrium with regard to agents' preference profiles over the entire plan space. Our empirical evaluation beyond these restricted scenarios shows, however, that the algorithm has much broader applicability as a method for plan improvement in general multiagent planning problems. Extensive empirical experiments in various domains illustrate the scalability of our method in both cases.

Post-traumatic Wolff-Parkinson-White syndrome description and case presentation

The ventricular pre-excitation syndrome (Wolff-Parkinson-White syndrome) is defined as a premature activation of the entire ventricular myocardium by a super-ventricular impulse. The premature activation is made by accessory conduction pathways that produce a short circuit in the normal nodo-hisian pathway. The accessory pathways are made of atrial myocardial fibers that have a higher conduction velocity and a refractory period shorter than the nodo-hisian structures. The accessory bundle can be single or multiple; it refers to congenital structures that can be dormant and they are often activated under the action of different agents. We present the case of a male aged 34 who was the victim of an aggression being hit with fists and feet. In this case, the Wolff-Parkinson-White syndrome has appeared as a sudden atrial fibrillation and left ventricular failure that appeared immediately after a traumatism of the face and legs. In this case the patient suffered from severe symptoms due to the appearance of the Wolff-Parkinson-White and required immediate hospitalization, medical treatment and ablation of the Paladino-Kent bundle. Key W ords: WPW syndrome, accessory pathways, traumatism

Social Reinforcement: Cascades, Entrapment, and Tipping

The actions of different agents sometimes reinforce each other. Examples are network effects and the threshold models used by sociologists as well as (Harvey) Leibenstein's “bandwagon effects.” We model such situations as a game with increasing differences, and show that tipping of equilibria, cascading, and clubs with entrapment are natural consequences of this mutual reinforcement. If there are several equilibria, one of which Pareto dominates, then the inefficient equilibria can be tipped to the efficient one, a result of interest in the context of coordination problems. We characterize the smallest tipping set. (JEL C72, D80, D85, Z13)