The evolution of strategic timing in collective-risk dilemmas

In collective-risk dilemmas, a group needs to collaborate over time to avoid a catastrophic event. This gives rise to a coordination game with many equilibria, including equilibria where no one contributes, and thus no measures against the catastrophe are taken. In this game, the timing of contributions becomes a strategic variable that allows individuals to interact and influence one another. Herein, we use evolutionary game theory to study the impact of strategic timing on equilibrium selection. Depending on the risk of catastrophe, we identify three characteristic regimes. For low risks, defection is the only equilibrium, whereas high risks promote equilibria with sufficient contributions. Intermediate risks pose the biggest challenge for cooperation. In this risk regime, the option to interact over time is critical; if individuals can contribute over several rounds, then the group has a higher chance to succeed, and the expected welfare increases. This positive effect of timing is of particular importance in larger groups, where successful coordination becomes increasingly difficul

Social dilemmas among unequals

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this record.Direct reciprocity is a powerful mechanism for evolution of cooperation, based on repeated interactions. It requires that interacting individuals are sufficiently equal, such that everyone faces similar consequences when they cooperate or defect. Yet inequality is ubiquitous among humansand is generally considered to undermine cooperation and welfar. Most previous models of reciprocity neglect inequality. They assume that individuals are the same in all relevant aspects. Here we introduce a general framework to study direct reciprocity among unequals. Our model allows for multiple sources of inequality. Subjects can differ in their endowments, their productivities, and in how much they benefit from public goods. We find that extreme inequality prevents cooperation. But if subjects differ in productivity, some endowment inequality can be necessary for cooperation to prevail. Our mathematical predictions are supported by a behavioral experiment where we vary the subjects’ endowments and their productivities. We observe that overall welfare is maximized when the two sources of heterogeneity are aligned, such that more productive individuals receive higher endowments. In contrast, when endowments and productivities are misaligned, cooperation quickly breaks down. Our findings have implications for policy-makers concerned with equity, efficiency, and public goods provisioning.European Research Council Start GrantGraph GamesAustrian Science Fund (FWF)Office of Naval ResearchJohn Templeton FoundationISTFELLOW program

Predictors of first recurrence of clostridium difficile infection: Implications for initial management

Symptomatic recurrence of Clostridium difficile infection (CDI) occurs in approximately 20 of patients and is challenging to treat. Identifying those at high risk could allow targeted initial management and improve outcomes. Adult toxin enzyme immunoassay-positive CDI cases in a population of approximately 600 000 persons from September 2006 through December 2010 were combined with epidemiological/clinical data. The cumulative incidence of recurrence ≥14 days after the diagnosis and/or onset of first-ever CDI was estimated, treating death without recurrence as a competing risk, and predictors were identified from cause-specific proportional hazards regression models. A total of 1678 adults alive 14 days after their first CDI were included; median age was 77 years, and 1191 (78) were inpatients. Of these, 363 (22) experienced a recurrence ≥14 days after their first CDI, and 594 (35) died without recurrence through March 2011. Recurrence risk was independently and significantly higher among patients admitted as emergencies, with previous gastrointestinal ward admission(s), last discharged 4-12 weeks before first diagnosis, and with CDI diagnosed at admission. Recurrence risk also increased with increasing age, previous total hours admitted, and C-reactive protein level at first CDI (all P <. 05). The 4-month recurrence risk increased by approximately 5 (absolute) for every 1-point increase in a risk score based on these factors. Risk factors, including increasing age, initial disease severity, and hospital exposure, predict CDI recurrence and identify patients likely to benefit from enhanced initial CDI treatment

The impact of the introduction of fidaxomicin on the management of Clostridium difficile infection in seven NHS secondary care hospitals in England: a series of local service evaluations.

Clostridium difficile infection (CDI) is associated with high mortality. Reducing incidence is a priority for patients, clinicians, the National Health Service (NHS) and Public Health England alike. In June 2012, fidaxomicin (FDX) was launched for the treatment of adults with CDI. The objective of this evaluation was to collect robust real-world data to understand the effectiveness of FDX in routine practice. In seven hospitals introducing FDX between July 2012 and July 2013, data were collected retrospectively from medical records on CDI episodes occurring 12 months before/after the introduction of FDX. All hospitalised patients aged ≥18 years with primary CDI (diarrhoea with presence of toxin A/B without a previous CDI in the previous 3 months) were included. Recurrence was defined as in-patient diarrhoea re-emergence requiring treatment any time within 3 months after the first episode. Each hospital had a different protocol for the use of FDX. In hospitals A and B, where FDX was used first line for all primary and recurrent episodes, the recurrence rate reduced from 10.6 % to 3.1 % and from 16.3 % to 3.1 %, with a significant difference in 28-day mortality from 18.2 % to 3.1 % (p < 0.05) and 17.3 % to 6.3 % (p < 0.05) for hospitals A and B, respectively. In hospitals using FDX in selected patients only, the changes in recurrence rates and mortality were less marked. The pattern of adoption of FDX appears to affect its impact on CDI outcome, with maximum reduction in recurrence and all-cause mortality where it is used as first-line treatment

Prediction Tools for Unfavourable Outcomes in Clostridium difficile Infection: A Systematic Review

CONTEXT: Identifying patients at risk for adverse outcomes of Clostridium difficile infection (CDI), including recurrence and death, will become increasingly important as novel therapies emerge, which are more effective than traditional approaches but very expensive. Clinical prediction rules (CPRs) can improve the accuracy of medical decision-making. Several CPRs have been developed for CDI, but none has gained a widespread acceptance. METHODS: We systematically reviewed studies describing the derivation or validation of CPRs for unfavourable outcomes of CDI, in medical databases (Medline, Embase, PubMed, Web of Science and Cochrane) and abstracts of conferences. RESULTS: Of 2945 titles and abstracts screened, 13 studies on the derivation of a CPR were identified: two on recurrences, five on complications (including mortality), five on mortality alone and one on response to treatment. Two studies on the validation of different severity indices were also retrieved. Most CPRs were developed as secondary analyses using cohorts assembled for other purposes. CPRs presented several methodological limitations that could explain their limited use in clinical practice. Except for leukocytosis, albumin and age, there was much heterogeneity in the variables used, and most studies were limited by small sample sizes. Eight models used a retrospective design. Only four studies reported the incidence of the outcome of interest, even if this is essential to evaluate the potential usefulness of a model in other populations. Only five studies performed multivariate analyses to adjust for confounders. CONCLUSIONS: The lack of weighing variables, of validation, calibration and measures of reproducibility, the weak validities and performances when assessed, and the absence of sensitivity analyses, all led to suboptimal quality and debatable utility of those CPRs. Evidence-based tools developed through appropriate prospective cohorts would be more valuable for clinicians than empirically-developed CPRs

Biomonitoring of complex occupational exposures to carcinogens: The case of sewage workers in Paris

<p>Abstract</p> <p>Background</p> <p>Sewage workers provide an essential service in the protection of public and environmental health. However, they are exposed to varied mixtures of chemicals; some are known or suspected to be genotoxics or carcinogens. Thus, trying to relate adverse outcomes to single toxicant is inappropriate. We aim to investigate if sewage workers are at increased carcinogenic risk as evaluated by biomarkers of exposure and early biological effects.</p> <p>Methods/design</p> <p>This cross sectional study will compare exposed sewage workers to non-exposed office workers. Both are voluntaries from Paris municipality, males, aged (20–60) years, non-smokers since at least six months, with no history of chronic or recent illness, and have similar socioeconomic status. After at least 3 days of consecutive work, blood sample and a 24-hour urine will be collected. A caffeine test will be performed, by administering coffee and collecting urines three hours after. Subjects will fill in self-administered questionnaires; one covering the professional and lifestyle habits while the a second one is alimentary. The blood sample will be used to assess DNA adducts in peripheral lymphocytes. The 24-hour urine to assess urinary 8-oxo-7, 8-dihydro-2'-deoxy-Guanosine (8-oxo-dG), and the in vitro genotoxicity tests (comet and micronucleus) using HeLa S3 or HepG2 cells. In parallel, occupational air sampling will be conducted for some Polycyclic Aromatic Hydrocarbons and Volatile Organic Compounds. A weekly sampling chronology at the offices of occupational medicine in Paris city during the regular medical visits will be followed. This protocol has been accepted by the French Est III Ethical Comitee with the number 2007-A00685-48.</p> <p>Discussion</p> <p>Biomarkers of exposure and of early biological effects may help overcome the limitations of environmental exposure assessment in very complex occupational or environmental settings.</p

Clostridium difficile infection.

Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota