Multiplayer Cost Games with Simple Nash Equilibria

Multiplayer games with selfish agents naturally occur in the design of distributed and embedded systems. As the goals of selfish agents are usually neither equivalent nor antagonistic to each other, such games are non zero-sum games. We study such games and show that a large class of these games, including games where the individual objectives are mean- or discounted-payoff, or quantitative reachability, and show that they do not only have a solution, but a simple solution. We establish the existence of Nash equilibria that are composed of k memoryless strategies for each agent in a setting with k agents, one main and k-1 minor strategies. The main strategy describes what happens when all agents comply, whereas the minor strategies ensure that all other agents immediately start to co-operate against the agent who first deviates from the plan. This simplicity is important, as rational agents are an idealisation. Realistically, agents have to decide on their moves with very limited resources, and complicated strategies that require exponential--or even non-elementary--implementations cannot realistically be implemented. The existence of simple strategies that we prove in this paper therefore holds a promise of implementability.Comment: 23 page

Dynamics of circulating TNF during adalimumab treatment using a drug-tolerant TNF assay

Patients with rheumatoid arthritis (RA) can be successfully treated with tumor necrosis factor (TNF) inhibitors, including the monoclonal antibody adalimumab. Once in remission, a proportion of patients can successfully discontinue treatment, indicating that blocking TNF is no longer required for disease control. To explore the dynamics of circulating TNF during adalimumab treatment, we developed a competition enzyme-linked immunosorbent assay that can quantify TNF in the presence of large amounts of TNF inhibitor, i.e., a “drug-tolerant” assay. In 193 consecutive adalimumab-treated patients with RA, we demonstrated that circulating TNF increased in average of &gt;50-fold upon treatment and reached a stable concentration in time for most patients. A similar increase in TNF was found in 30 healthy volunteers after one dose of adalimumab. This implies that TNF in circulation during anti-TNF treatment is not primarily associated with disease activity. During treatment, TNF was in complex with adalimumab and could be recovered as inactive 3:1 adalimumab-TNF complexes. No quantitative association was found between TNF and adalimumab concentrations. Low TNF concentrations at week 4 were associated with a higher frequency of antidrug antibodies (ADAs) at subsequent time points, less frequent methotrexate use at baseline, and less frequent remission after 52 weeks. Also in healthy volunteers, early low TNF concentrations are associated with ADAs. In conclusion, longitudinal TNF concentrations are mostly stable during adalimumab treatment and may therefore not predict successful treatment discontinuation. However, early low TNF is strongly associated with ADA formation and may be used as timely predictor of nonresponse toward adalimumab treatment.</p

Cytotoxic lymphocytes in B-cell chronic lymphocytic leukemia

The occurrence of cytotoxic lymphocyte subpopulations (i.e., CD 16+, CD57+ and cytotoxic CD 8+) was studied in the peripheral blood of 18 B-cell chronic lymphocytic leukemia (B-CLL) patients. The absolute numbers of CD 57+, CD 16+ and cytotoxic CD 8+ lymphocytes were increased in the peripheral blood of untreated patients as compared with healthy donors, suggesting a causal relation with the accumulation of malignant B-cells. For 5 B-CLL patients and 5 hematological normal donors, the lymphocyte subpopulations in peripheral blood, lymph nodes and bone marrow were determined. A significant immune response was observed in the lymph nodes of the patients, as reflected by the CD 3+ lymphocytes, which were 1.7–27 times larger in the patients lymph nodes than in their peripheral blood and bone marrow. In contrast, with peripheral blood this was mainly caused by an increase in CD 4+ lymphocytes. The CD 57 lymphocytes in the lymph nodes of the patients had abnormal orthogonal light-scattering signals and an abnormal density of CD 57+ receptors in comparison with their peripheral blood CD 57+ lymphocytes or the CD57+ lymphocytes in the peripheral blood, bone marrow and tonsils of the hematological normal donors. This study shows that although a significant increase of cytotoxic lymphocytes in the peripheral blood of B-CLL patients is observed, the actual distributions of the non-malignant lymphocytes can be quite different at the actual tumor sites, i.e., bone marrow and lymph node

Clinical disorders affecting mesopic vision

Vision in the mesopic range is affected by a number of inherited and acquired clinical disorders. We review these conditions and summarize the historical background, describing the clinical characteristics alongside the genetic basis and molecular biological mechanisms giving rise to rod and cone dysfunction relevant to twilight vision. The current diagnostic gold standards for each disease are discussed and curative and symptomatic treatment strategies are summarized

LNCS

We study turn-based stochastic zero-sum games with lexicographic preferences over reachability and safety objectives. Stochastic games are standard models in control, verification, and synthesis of stochastic reactive systems that exhibit both randomness as well as angelic and demonic non-determinism. Lexicographic order allows to consider multiple objectives with a strict preference order over the satisfaction of the objectives. To the best of our knowledge, stochastic games with lexicographic objectives have not been studied before. We establish determinacy of such games and present strategy and computational complexity results. For strategy complexity, we show that lexicographically optimal strategies exist that are deterministic and memory is only required to remember the already satisfied and violated objectives. For a constant number of objectives, we show that the relevant decision problem is in NP∩coNP , matching the current known bound for single objectives; and in general the decision problem is PSPACE -hard and can be solved in NEXPTIME∩coNEXPTIME . We present an algorithm that computes the lexicographically optimal strategies via a reduction to computation of optimal strategies in a sequence of single-objectives games. We have implemented our algorithm and report experimental results on various case studies

Norovirus outbreak in a natural playground: A One Health approach

Norovirus constitutes the most frequently identified infectious cause of disease outbreaks associated with untreated recreational water. When investigating outbreaks related to surface water, a One Health approach is insightful. Historically, there has been a focus on potential contamination of recreational water by bird droppings and a recent publication demonstrating human noroviruses in bird faeces suggested this should be investigated in future water-related norovirus outbreaks. Here, we describe a One Health approach investigating a norovirus outbreak in a natural playground. On social media, a large amount of waterfowl were reported to defecate near these playground premises leading to speculations about their potential involvement. Surface water, as well as human and bird faecal specimens, was tested for human noroviruses. Norovirus was found to be the most likely cause of the outbreak but there was no evidence for transmission via waterfowl. Cases had become known on social media prior to notification to the public health service underscoring the potential of online media as an early warning system. In view of known risk factors, advice was given for future outbreak investigations and natural playgroun