Game Theory of Social Distancing in Response to an Epidemic

Social distancing practices are changes in behavior that prevent disease transmission by reducing contact rates between susceptible individuals and infected individuals who may transmit the disease. Social distancing practices can reduce the severity of an epidemic, but the benefits of social distancing depend on the extent to which it is used by individuals. Individuals are sometimes reluctant to pay the costs inherent in social distancing, and this can limit its effectiveness as a control measure. This paper formulates a differential-game to identify how individuals would best use social distancing and related self-protective behaviors during an epidemic. The epidemic is described by a simple, well-mixed ordinary differential equation model. We use the differential game to study potential value of social distancing as a mitigation measure by calculating the equilibrium behaviors under a variety of cost-functions. Numerical methods are used to calculate the total costs of an epidemic under equilibrium behaviors as a function of the time to mass vaccination, following epidemic identification. The key parameters in the analysis are the basic reproduction number and the baseline efficiency of social distancing. The results show that social distancing is most beneficial to individuals for basic reproduction numbers around 2. In the absence of vaccination or other intervention measures, optimal social distancing never recovers more than 30% of the cost of infection. We also show how the window of opportunity for vaccine development lengthens as the efficiency of social distancing and detection improve

Mifamurtide for the treatment of nonmetastatic osteosarcoma

International audienceINTRODUCTION: The standard treatment for osteosarcoma requires both macroscopic surgical wide resection and postoperative multi-drug chemotherapy in neoadjuvant and adjuvant settings. However, the 5-year event-free survival has remained at a plateau of 60-70% of patients with nonmetastatic osteosarcoma for more than 30 years. AREAS COVERED: Mifamurtide (liposomal muramyl tripeptide phosphatidylethanolamine; L-MTP-PE) is a new agent. L-MTP-PE is a nonspecific immunomodulator, which is a synthetic analog of a component of bacterial cell walls. L-MTP-PE activates macrophages and monocytes as a potent activator of immune response in addition to standard chemotherapy. It also improves the overall survival from 70 to 78% and results in a one-third reduction in the risk of death from osteosarcoma. This review summarizes the most recent findings about L-MTP-PE and its therapeutic application for nonmetastatic osteosarcoma. EXPERT OPINION: Recently, L-MTP-PE has been approved in Europe for the treatment of nonmetastatic osteosarcoma with chemotherapy. L-MTP-PE in combination with traditional treatment is expected to go mainstream and to be beneficial for patients with osteosarcoma. Information about potential benefit regarding mifamurtide use in the neoadjuvant setting (i.e., before surgery) and/or usefulness of L-MTP-PE in metastatic in relapsed and metastatic osteosarcoma requires analysis of expanded access and/or future clinical trials of L-MTP-PE in high-burden and low-burden situations

The influence of low-grade glioma on resting state oscillatory brain activity: a magnetoencephalography study

Purpose In the present MEG-study, power spectral analysis of oscillatory brain activity was used to compare resting state brain activity in both low-grade glioma (LGG) patients and healthy controls. We hypothesized that LGG patients show local as well as diffuse slowing of resting state brain activity compared to healthy controls and that particularly global slowing correlates with neurocognitive dysfunction. Patient and methods Resting state MEG recordings were obtained from 17 LGG patients and 17 age-, sex-, and education-matched healthy controls. Relative spectral power was calculated in the delta, theta, upper and lower alpha, beta, and gamma frequency band. A battery of standardized neurocognitive tests measuring 6 neurocognitive domains was administered. Results LGG patients showed a slowing of the resting state brain activity when compared to healthy controls. Decrease in relative power was mainly found in the gamma frequency band in the bilateral frontocentral MEG regions, whereas an increase in relative power was found in the theta frequency band in the left parietal region. An increase of the relative power in the theta and lower alpha band correlated with impaired executive functioning, information processing, and working memory. Conclusion LGG patients are characterized by global slowing of their resting state brain activity and this slowing phenomenon correlates with the observed neurocognitive deficits

Effect of the G375C and G346E Achondroplasia Mutations on FGFR3 Activation

Two mutations in FGFR3, G380R and G375C are known to cause achondroplasia, the most common form of human dwarfism. The G380R mutation accounts for 98% of the achondroplasia cases, and thus has been studied extensively. Here we study the effect of the G375C mutation on the phosphorylation and the cross-linking propensity of full-length FGFR3 in HEK 293 cells, and we compare the results to previously published results for the G380R mutant. We observe identical behavior of the two achondroplasia mutants in these experiments, a finding which supports a direct link between the severity of dwarfism phenotypes and the level and mechanism of FGFR3 over-activation. The mutations do not increase the cross-linking propensity of FGFR3, contrary to previous expectations that the achondroplasia mutations stabilize the FGFR3 dimers. Instead, the phosphorylation efficiency within un-liganded FGFR3 dimers is increased, and this increase is likely the underlying cause for pathogenesis in achondroplasia. We further investigate the G346E mutation, which has been reported to cause achondroplasia in one case. We find that this mutation does not increase FGFR3 phosphorylation and decreases FGFR3 cross-linking propensity, a finding which raises questions whether this mutation is indeed a genetic cause for human dwarfism

Response of littoral chironomid community and organic matter to late glacial lake level and environmental changes at Lago dell'Accesa (Tuscany, Italy).

International audienceThis study focuses on the response of lacustrine littoral chironomid communities to late glacial changes in limnological, environmental and climate conditions in the Mediterranean context. Late glacial chironomid (Diptera: Chironomidae) assemblages, organic petrography and geochemistry were analysed in a sediment core from the littoral zone of Lago dell'Accesa (Tuscany, Italy), where the lake-level fluctuations and the vegetation history have been previously reconstructed. Comparison of the chironomid stratigraphy to other proxies (pollen assemblages, organic petrography and geochemistry, lake-level) and regional climate reconstruction suggested the predominant influence of lake-level changes on the littoral chironomid fauna. The main lowering events that occurred during the Oldest and the Younger Dryas were followed by higher proportions of taxa typical of littoral habitats. A complementary study of organic matter suggested the indirect impact of lake-level on the chironomids through changes in humic status and habitat characteristics, such as the type of substrate and aquatic macrophyte development. Several chironomid taxa, such as Glyptotendipes, Microtendipes and Cricotopus type patens, were identified as possible indicators of low lake-level in the late glacial records. Nevertheless, this study suggested that parallel analyses of organic matter and chironomid assemblages may be needed to circumvent misinterpretation of littoral chironomid assemblage stratigraphy. There was a weak response of the chironomid assemblages to small lake-level lowerings that corresponded to the Older Dryas and Preboreal oscillations. A higher level of determination, e.g. to the species group level, may be necessary to increase the sensibility of the indicators to lake-level changes

Antibacterial activity of sucralfate versus aluminum chloride in simulated gastric fluid

Studies have previously demonstrated that sucralfate possesses intrinsic antibacterial activity. This study was designed to indirectly assess whether aluminum is the active antibacterial component of sucralfate and to further evaluate factors that may influence this agent's antibacterial activity. Utilizing an in vitro model, the antibacterial activity of sucralfate, an equivalent quantity of aluminum in the form of aluminum chloride, and a control were compared. In addition, the influences of bacterial species ( Enterobacter cloacae and Pseudomonas aeruginosa ), time (0–24 h) and environmental pH (3, 5, 7) on the agents' antibacterial activities were evaluated. Equivalent quantities of aluminum, as either sucralfate or aluminum chloride, were added to two of three flasks containing approximately 10 5 cfu/ml of bacteria in pH-adjusted simulated gastric fluid. The third flask served as a control. Samples were obtained over 24 h, diluted and subcultured onto agar plates. The experiments demonstrated that bacterial growth was influenced by pH, time and treatment (aluminum chloride or sucralfate). Regardless of pH or bacterial species, bacterial death occurred within 20 min following the addition of aluminum chloride. In contrast, bacterial death following the addition of sucralfate was more variable and appeared to be pH dependent. In conclusion, sucralfate and aluminum chloride both possess antibacterial activity, even at pH values that normally support bacterial growth in gastric fluid. Although differences in the antibacterial activity of the two agents may in part be related to drug-induced changes in pH, these differences also support data suggesting that aluminum release from sucralfate is incomplete and is dependent on pH.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47895/1/10096_2005_Article_BF02111825.pd

Memory in Microbes: Quantifying History-Dependent Behavior in a Bacterium

Memory is usually associated with higher organisms rather than bacteria. However, evidence is mounting that many regulatory networks within bacteria are capable of complex dynamics and multi-stable behaviors that have been linked to memory in other systems. Moreover, it is recognized that bacteria that have experienced different environmental histories may respond differently to current conditions. These “memory” effects may be more than incidental to the regulatory mechanisms controlling acclimation or to the status of the metabolic stores. Rather, they may be regulated by the cell and confer fitness to the organism in the evolutionary game it participates in. Here, we propose that history-dependent behavior is a potentially important manifestation of memory, worth classifying and quantifying. To this end, we develop an information-theory based conceptual framework for measuring both the persistence of memory in microbes and the amount of information about the past encoded in history-dependent dynamics. This method produces a phenomenological measure of cellular memory without regard to the specific cellular mechanisms encoding it. We then apply this framework to a strain of Bacillus subtilis engineered to report on commitment to sporulation and degradative enzyme (AprE) synthesis and estimate the capacity of these systems and growth dynamics to ‘remember’ 10 distinct cell histories prior to application of a common stressor. The analysis suggests that B. subtilis remembers, both in short and long term, aspects of its cell history, and that this memory is distributed differently among the observables. While this study does not examine the mechanistic bases for memory, it presents a framework for quantifying memory in cellular behaviors and is thus a starting point for studying new questions about cellular regulation and evolutionary strategy