Cooperation for public goods under uncertainty

Everyone wants clean air, peace and other public goods but is tempted to freeride on others' efforts. The usual way out of this dilemma is to impose norms, maintain reputations and incentivize individuals to contribute. In situations of high uncertainty, however, such as confrontations of protesters with a dictatorial regime, the usual measures are not feasible, but cooperation can be achieved nevertheless. We use an Ising model with asymmetric spins that represent cooperation and defection to show numerically how public goods can be realized. Under uncertainty, people use the heuristic of conformity. The turmoil of a confrontation causes some individuals to cooperate accidentally, and at a critical level of turmoil, they entail a cascade of cooperation. This critical level is much lower in small networks

Epidemic space

The aim of this article is to highlight the importance of 'spatiality' in understanding the materialization of risk society and cultivation of risk sensibilities. More specifically it provides a cultural analysis of pathogen virulence (as a social phenomenon) by means of tracing and mapping the spatial flows that operate in the uncharted zones between the microphysics of infection and the macrophysics of epidemics. It will be argued that epidemic space consists of three types of forces: the vector, the index and the vortex. It will draw on Latour's Actor Network Theory to argue that epidemic space is geared towards instability when the vortex (of expanding associations and concerns) displaces the index (of finding a single cause)

Are we losing the battle against cardiometabolic disease? The case for a paradigm shift in primary prevention

Kraushaar LE, Krämer A. Are we losing the battle against cardiometabolic disease? The case for a paradigm shift in primary prevention. BMC Public Health. 2009;9(1):64.Background: Cardiovascular and diabetic disease are the leading and preventable causes of death worldwide. The currently prognosticated dramatic increase in disease burden over the next two decades, however, bespeaks a low confidence in our prevention ability. This conflicts with the almost enthusiastic reporting of study results, which demonstrate substantial risk reductions secondary to simple lifestyle changes. Discussion: There is a case to be made for a disregard of the difference between statistical significance and clinical relevance of the reported data. Nevertheless, lifestyle change remains the main weapon in our battle against the epidemic of cardiometabolic disease. But along the way from risk screening to intervention to maintenance the compound inefficiencies of current primary preventive strategies marginalize their impact. Summary: Unless we dramatically change the ways in which we deploy preventive interventions we will inevitably lose the battle. In this paper we will argue for three provocative strategy changes, namely (a) the disbanding of screening in favor of population-wide enrollment into preventive interventions, (b) the substitution of the current cost utility analysis for a return-on-investment centered appraisal of interventions, and (c) the replacement of standardized programs modeled around acute care by individualized and perpetual interventions

Anti-ischemic therapy and stress testing: pathophysiologic, diagnostic and prognostic implications

Anti-ischemic therapy, in particular beta-blockers, is the most commonly employed drug for the control of myocardial ischemia in patients with stable coronary artery disease. Its widespread use also in patients with suspected coronary artery disease has important practical, clinical diagnostic and prognostic implications because diagnostic tests are heavily influenced by its effects. In the present review, the pathophysiological mechanisms of ischemia protection by antianginal therapy are described. Not all stressors are created equal in front of the different classes of antianginal drugs and on their turn the different classes of drugs exert different levels of protection on inducible ischemia. Several clinical implications can be drawn: From the diagnostic viewpoint antianginal therapy decreases test sensitivity, offsetting the real ischemic burden for a too high percentage of false negative tests. From the prognostic viewpoint test positivity in medical therapy identifies a group of subjects at higher risk of experiencing cardiac death and positivity on medical therapy can be considered a parameter of ischemia severity. Nonetheless in patients with known coronary artery disease the ability of antianginal therapy to modify the ischemic threshold at stress testing represent a powerful means to assess therapy efficacy. From a practical viewpoint, the use of antianginal therapy at time of testing has advantages and disadvantages which are largely dependent on the purpose a test is performed: if the purpose of testing is to diagnose ischemia, it should be performed in the absence of antianginal medications. If the purpose of testing is to assess the protective effects of antianginal therapy, the test should be performed on medications

Estimating the malaria risk of African mosquito movement by air travel

BACKGROUND: The expansion of global travel has resulted in the importation of African Anopheles mosquitoes, giving rise to cases of local malaria transmission. Here, cases of 'airport malaria' are used to quantify, using a combination of global climate and air traffic volume, where and when are the greatest risks of a Plasmodium falciparum-carrying mosquito being importated by air. This prioritises areas at risk of further airport malaria and possible importation or reemergence of the disease. METHODS: Monthly data on climate at the World's major airports were combined with air traffic information and African malaria seasonality maps to identify, month-by-month, those existing and future air routes at greatest risk of African malaria-carrying mosquito importation and temporary establishment. RESULTS: The location and timing of recorded airport malaria cases proved predictable using a combination of climate and air traffic data. Extending the analysis beyond the current air network architecture enabled identification of the airports and months with greatest climatic similarity to P. falciparum endemic regions of Africa within their principal transmission seasons, and therefore at risk should new aviation routes become operational. CONCLUSION: With the growth of long haul air travel from Africa, the identification of the seasonality and routes of mosquito importation is important in guiding effective aircraft disinsection and vector control. The recent and continued addition of air routes from Africa to more climatically similar regions than Europe will increase movement risks. The approach outlined here is capable of identifying when and where these risks are greatest

Molecular basis of structure and function of the microvillus membrane of intestinal epithelial cells

Correlation of molecular structure with biochemical functions of the plasma membrane of the microvilli of intestinal epithelial cells has been investigated by biochemical and electron microscopic procedures. Repeating particles, measuring approximately 60 &#197;in diameter, were found on the surface of the microvilli membrane which had been isolated or purified from rabbit intestinal epithelial cells and negatively stained with phosphotungstic acid. These particles were proved to be inherent components of the microvillus membrane, attached to the outer surface of its trilaminar structure, and were designated as the elementary particles of the microvilli of intestinal epithelial cells. Biochemical and electron microscopic identification of these elementary particles has been carried out by isolation of the elementary particles with papain from the isolated microvillus membrane, followed by purification of the particles by chromatographies on DEAE-cellulose and Sephadex columns. The partially purified particles containing invertase and leucine aminopeptidase are similar in size and structure to those of the elementary particles in the microvillus membrane. Evidence indicates that each of the elementary particles coincide with or include an enzyme molecule such as disaccharidase or peptidase, which carry out the terminal hydrolytic digestion of carbohydrates and proteins, respectively, on the surface of the microvillus membrane. Magnesium ionactivated adenosine triphosphatase and alkaline phosphatase cannot be solubilized with papain but remains in the smooth-surface membrane after the elementary particles have been removed. Cytochemical electron microscopic observation revealed that the active site of magnesium ion-activated adenosine triphosphatase is localized predominantly in the inner surface of the trilaminar structure of the microvillus membrane.</p

Temporal regularity of the environment drives time perception

It’s reasonable to assume that a regularly paced sequence should be perceived as regular, but here we show that perceived regularity depends on the context in which the sequence is embedded. We presented one group of participants with perceptually regularly paced sequences, and another group of participants with mostly irregularly paced sequences (75% irregular, 25% regular). The timing of the final stimulus in each sequence could be varied. In one experiment, we asked whether the last stimulus was regular or not. We found that participants exposed to an irregular environment frequently reported perfectly regularly paced stimuli to be irregular. In a second experiment, we asked participants to judge whether the final stimulus was presented before or after a flash. In this way, we were able to determine distortions in temporal perception as changes in the timing necessary for the sound and the flash to be perceived synchronous. We found that within a regular context, the perceived timing of deviant last stimuli changed so that the relative anisochrony appeared to be perceptually decreased. In the irregular context, the perceived timing of irregular stimuli following a regular sequence was not affected. These observations suggest that humans use temporal expectations to evaluate the regularity of sequences and that expectations are combined with sensory stimuli to adapt perceived timing to follow the statistics of the environment. Expectations can be seen as a-priori probabilities on which perceived timing of stimuli depend

Civil conflict and sleeping sickness in Africa in general and Uganda in particular

Conflict and war have long been recognized as determinants of infectious disease risk. Re-emergence of epidemic sleeping sickness in sub-Saharan Africa since the 1970s has coincided with extensive civil conflict in affected regions. Sleeping sickness incidence has placed increasing pressure on the health resources of countries already burdened by malaria, HIV/AIDS, and tuberculosis. In areas of Sudan, the Democratic Republic of the Congo, and Angola, sleeping sickness occurs in epidemic proportions, and is the first or second greatest cause of mortality in some areas, ahead of HIV/AIDS. In Uganda, there is evidence of increasing spread and establishment of new foci in central districts. Conflict is an important determinant of sleeping sickness outbreaks, and has contributed to disease resurgence. This paper presents a review and characterization of the processes by which conflict has contributed to the occurrence of sleeping sickness in Africa. Conflict contributes to disease risk by affecting the transmission potential of sleeping sickness via economic impacts, degradation of health systems and services, internal displacement of populations, regional insecurity, and reduced access for humanitarian support. Particular focus is given to the case of sleeping sickness in south-eastern Uganda, where incidence increase is expected to continue. Disease intervention is constrained in regions with high insecurity; in these areas, political stabilization, localized deployment of health resources, increased administrative integration and national capacity are required to mitigate incidence. Conflict-related variables should be explicitly integrated into risk mapping and prioritization of targeted sleeping sickness research and mitigation initiatives

Checkpoint Signaling, Base Excision Repair, and PARP Promote Survival of Colon Cancer Cells Treated with 5-Fluorodeoxyuridine but Not 5-Fluorouracil

The fluoropyrimidines 5-fluorouracil (5-FU) and FdUrd (5-fluorodeoxyuridine; floxuridine) are the backbone of chemotherapy regimens for colon cancer and other tumors. Despite their widespread use, it remains unclear how these agents kill tumor cells. Here, we have analyzed the checkpoint and DNA repair pathways that affect colon tumor responses to 5-FU and FdUrd. These studies demonstrate that both FdUrd and 5-FU activate the ATR and ATM checkpoint signaling pathways, indicating that they cause genotoxic damage. Notably, however, depletion of ATM or ATR does not sensitize colon cancer cells to 5-FU, whereas these checkpoint pathways promote the survival of cells treated with FdUrd, suggesting that FdUrd exerts cytotoxicity by disrupting DNA replication and/or inducing DNA damage, whereas 5-FU does not. We also found that disabling the base excision (BER) repair pathway by depleting XRCC1 or APE1 sensitized colon cancer cells to FdUrd but not 5-FU. Consistent with a role for the BER pathway, we show that small molecule poly(ADP-ribose) polymerase 1/2 (PARP) inhibitors, AZD2281 and ABT-888, remarkably sensitized both mismatch repair (MMR)-proficient and -deficient colon cancer cell lines to FdUrd but not to 5-FU. Taken together, these studies demonstrate that the roles of genotoxin-induced checkpoint signaling and DNA repair differ significantly for these agents and also suggest a novel approach to colon cancer therapy in which FdUrd is combined with a small molecule PARP inhibitor

How does it feel to act together?

This paper on the phenomenology of joint agency proposes a foray into a little explored territory at the intersection of two very active domains of research: joint action and sense of agency. I explore two ways in which our experience of joint agency may differ from our experience of individual agency. First, the mechanisms of action specification and control involved in joint action are typically more complex than those present in individual actions, since it is crucial for joint action that people coordinate their plans and actions. I discuss the implications that these coordination requirements might have for the strength of the sense of agency an agent may experience for a joint action. Second, engagement in joint action may involve a transformation of agentive identity and a partial or complete shift from a sense of self-agency to a sense of we-agency. I discuss several factors that may contribute to shaping our sense of agentive identity in joint action