Full agreement and the provision of threshold public goods

We report threshold public good experiments in which group members not only need to be individually willing to contribute enough to provide the public good but also have to agree with each other on what every group members should contribute. We find strong support to the hypothesis that full agreement increases successful provision, although it takes a few repetitions before group members can successfully coordinate. This is consistent with our theoretical results that full agreement works because it increases criticality of each individual decision. The existence of a focal point makes it possible for the group members to successfully coordinate.Public good, threshold, full agreement, focal point, experiment, coordination

Threshold public good games and impulse balance theory

We propose and develop a model of behavior in threshold public good games. The model draws on learning direction theory and impulse balance theory. We find good support for the model and demonstrate that it can explain the success rates observed in threshold public good experiments. The model is applied in a variety of dierent settings : we compare games with a full refund to those with no refund, consider changes in relative endowment, and consider changes in the step return and net reward.Public good, threshold, learning direction theory, impulse balance theory, counterfactual thinking

Reconstructing transmission trees for communicable diseases using densely sampled genetic data.

Whole genome sequencing of pathogens from multiple hosts in an epidemic offers the potential to investigate who infected whom with unparalleled resolution, potentially yielding important insights into disease dynamics and the impact of control measures. We considered disease outbreaks in a setting with dense genomic sampling, and formulated stochastic epidemic models to investigate person-to-person transmission, based on observed genomic and epidemiological data. We constructed models in which the genetic distance between sampled genotypes depends on the epidemiological relationship between the hosts. A data augmented Markov chain Monte Carlo algorithm was used to sample over the transmission trees, providing a posterior probability for any given transmission route. We investigated the predictive performance of our methodology using simulated data, demonstrating high sensitivity and specificity, particularly for rapidly mutating pathogens with low transmissibility. We then analyzed data collected during an outbreak of methicillin-resistant Staphylococcus aureus in a hospital, identifying probable transmission routes and estimating epidemiological parameters. Our approach overcomes limitations of previous methods, providing a framework with the flexibility to allow for unobserved infection times, multiple independent introductions of the pathogen, and within-host genetic diversity, as well as allowing forward simulation.Funding received from the following: The European Community [Mastering Hospital Antimicrobial Resistance (MOSAR) network contract LSHP-CT-2007-037941]. The National Institute of General Medical Sciences of the National Institutes of Health under award number U54GM088558. The UK Medical Research Council (Unit Programme number U105260566). The UKCRC Translational Infection Research Initiative (MRC Grant number G1000803) and Public Health England. The Medical Research Council and Department for International Development (Grant number MR/K006924/1). The Mahidol Oxford Tropical Medicine Research Unit is part of the Wellcome Trust Major Overseas Programme in SE Asia (Grant number 106698/Z/14/Z).This is the final version of the article. It first appeared from the Institute of Mathematical Statistics via http://dx.doi.org/10.1214/15-AOAS89

Impact of infectious diseases consultation on the management of Staphylococcus aureus bacteraemia in children.

OBJECTIVES: Infectious diseases consultation (IDC) in adults with Staphylococcus aureus bacteraemia (SAB) has been shown to improve management and outcome. The aim of this study was to evaluate the impact of IDC on the management of SAB in children. STUDY DESIGN: Observational cohort study of children with SAB. SETTING: Cambridge University Hospitals National Health Service (NHS) Foundation Trust, a large acute NHS Trust in the UK. PARTICIPANTS: All children with SAB admitted to the Cambridge University Hospitals NHS Foundation Trust between 16 July 2006 and 31 December 2012. METHODS: Children with SAB between 2006 and 31 October 2009 were managed by routine clinical care (pre-IDC group) and data were collected retrospectively by case notes review. An IDC service for SAB was introduced in November 2009. All children with SAB were reviewed regularly and data were collected prospectively (IDC group) until 31 December 2012. Baseline characteristics, quality metrics and outcome were compared between the pre-IDC group and IDC group. RESULTS: There were 66 episodes of SAB in 63 children-28 patients (30 episodes) in the pre-IDC group, and 35 patients (36 episodes) in the IDC group. The median age was 3.4 years (IQR 0.2-10.7 years). Patients in the IDC group were more likely to have echocardiography performed, a removable focus of infection identified and to receive a longer course of intravenous antimicrobial therapy. There were no differences in total duration of antibiotic therapy, duration of hospital admission or outcome at 30 or 90 days following onset of SAB. CONCLUSIONS: IDC resulted in improvements in the investigation and management of SAB in children.This work was supported by grants from the UK Clinical Research Collaboration (UKCRC) Translational Infection Research Initiative (TIRI); the Medical Research Council (G1000803), with contributions from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research (NIHR) on behalf of the UK Department of Health, and the Chief Scientist of the Scottish Government Health Directorate; the Public Health England; and the NIHR Cambridge Biomedical Research Centre

Duration of exposure to multiple antibiotics is associated with increased risk of VRE bacteraemia: a nested case-control study.

BACKGROUND: VRE bacteraemia has a high mortality and continues to defy control. Antibiotic risk factors for VRE bacteraemia have not been adequately defined. We aimed to determine the risk factors for VRE bacteraemia focusing on duration of antibiotic exposure. METHODS: A retrospective matched nested case-control study was conducted amongst hospitalized patients at Cambridge University Hospitals NHS Foundation Trust (CUH) from 1 January 2006 to 31 December 2012. Cases who developed a first episode of VRE bacteraemia were matched 1:1 to controls by length of stay, year, specialty and ward type. Independent risk factors for VRE bacteraemia were evaluated using conditional logistic regression. RESULTS: Two hundred and thirty-five cases were compared with 220 controls. Duration of exposure to parenteral vancomycin, fluoroquinolones and meropenem was independently associated with VRE bacteraemia. Compared with patients with no exposure to vancomycin, those who received courses of 1-3 days, 4-7 days or >7 days had a stepwise increase in risk of VRE bacteraemia [conditional OR (cOR) 1.2 (95% CI 0.4-3.8), 3.8 (95% CI 1.2-11.7) and 6.6 (95% CI 1.9-22.8), respectively]. Other risk factors were: presence of a central venous catheter (CVC) [cOR 8.7 (95% CI 2.6-29.5)]; neutropenia [cOR 15.5 (95% CI 4.2-57.0)]; hypoalbuminaemia [cOR 8.5 (95% CI 2.4-29.5)]; malignancy [cOR 4.4 (95% CI 1.6-12.0)]; gastrointestinal disease [cOR 12.4 (95% CI 4.2-36.8)]; and hepatobiliary disease [cOR 7.9 (95% CI 2.1-29.9)]. CONCLUSIONS: Longer exposure to vancomycin, fluoroquinolones or meropenem was associated with VRE bacteraemia. Antimicrobial stewardship interventions targeting high-risk antibiotics are required to complement infection control procedures against VRE bacteraemia

(Fluoro)quinolones and quinolone resistance genes in the aquatic environment: a river catchment perspective.

This study provides an insight into the prevalence of (fluoro)quinolones (FQs) and their specific quinolone qnrS resistance gene in the Avon river catchment area receiving treated wastewater from 5 wastewater treatment plants (WWTPs), serving 1.5 million people and accounting for 75% of inhabitants living in the catchment area in the South West of England. Ofloxacin, ciprofloxacin, nalidixic acid and norfloxacin were found to be ubiquitous with daily loads reaching a few hundred g/day in wastewater influent and tens of g/day in receiving waters. This was in contrast to other FQs analysed: flumequine, nadifloxacin, lomefloxacin, ulifloxacin, prulifloxacin, besifloxacin and moxifloxacin, which were hardly quantified. Enantiomeric profiling revealed that ofloxacin was enriched with the S-(−)-enantiomer, likely deriving from its prescription as the more potent enantiomerically pure levofloxacin, alongside racemic ofloxacin. While ofloxacin's enantiomeric fraction (EF) remained constant, high stereoselectivity was observed in the case of its metabolite ofloxacin-N-oxide. The removal efficiency of quinolones during wastewater treatment at 5 WWTPs utilising either trickling filters (TF) or activated sludge (AS), was compound and wastewater treatment process dependent, with AS providing better efficiency than TF. The qnrS resistance gene was ubiquitous in wastewater. Its removal was WWTP treatment process dependent with TF performing best and resulting in significant removal of the gene (from 28 to 75%). AS underperformed with only 9% removal in the case of activated sludge and actual increase in the gene copy number within sequencing batch reactors (SBRs). Interestingly, the data suggests that higher removal of antibiotics could be linked with high prevalence of the gene (SBR and WWTP E) and vice versa, low removal of antibiotic is correlated with lower prevalence of the gene in wastewater effluent (TF, WWTP B and D). This is especially prominent in the case of ofloxacin and could indicate that AS might be facilitating antimicrobial resistance (AMR) prevalence to higher extent than TF. Wastewater-based epidemiology (WBE) was also applied to monitor any potential misuse (e.g. direct disposal) of FQs in the catchment. In most cases higher use of antibiotics with respect to official statistics (i.e. ciprofloxacin, ofloxacin) was observed, which suggests that FQs management practice require further attention

Development of an anti-CAR antibody response in SIV-infected rhesus macaques treated with CD4-MBL CAR/CXCR5 T cells

T cells expressing a simian immunodeficiency (SIV)-specific chimeric antigen receptor (CAR) and the follicular homing molecule, CXCR5, were infused into antiretroviral therapy (ART) suppressed, SIV-infected rhesus macaques to assess their ability to localize to the lymphoid follicle and control the virus upon ART interruption. While the cells showed evidence of functionality, they failed to persist in the animals beyond 28 days. Development of anti-CAR antibodies could be responsible for the lack of persistence. Potential antigenic sites on the anti-SIV CAR used in these studies included domains 1 and 2 of CD4, the carbohydrate recognition domain (CRD) of mannose-binding lectin (MBL), and an extracellular domain of the costimulatory molecule, CD28, along with short linker sequences. Using a flow cytometry based assay and target cells expressing the CAR/CXCR5 construct, we examined the serum of the CD4-MBL CAR/CXCR5-T cell treated animals to determine that the animals had developed an anti-CAR antibody response after infusion. Binding sites for the anti-CAR antibodies were identified by using alternative CARs transduced into target cells and by preincubation of the target cells with a CD4 blocking antibody. All of the treated animals developed antibodies in their serum that bound to CD4-MBL CAR/CXCR5 T cells and the majority were capable of inducing an ADCC response. The CD4 antibody-blocking assay suggests that the dominant immunogenic components of this CAR are the CD4 domains with a possible additional site of the CD28 domain with its linker. This study shows that an anti-drug antibody (ADA) response can occur even when using self-proteins, likely due to novel epitopes created by abridged self-proteins and/or the self-domain of the CAR connection to a small non-self linker. While in our study, there was no statistically significant correlation between the ADA response and the persistence of the CD4-MBL CAR/CXCR5-T cells in rhesus macaques, these findings suggest that the development of an ADA response could impact the long-term persistence of self-based CAR immunotherapies

Efficiency in a forced contribution threshold public good game

We contrast and compare three ways of predicting efficiency in a forced contribution threshold public good game. The three alternatives are based on ordinal potential, quantal response and impulse balance theory. We report an experiment designed to test the respective predictions and find that impulse balance gives the best predictions. A simple expression detailing when enforced contributions result in high or low efficiency is provided

Full Agreement and the Provision of Threshold Public Goods

The experimental evidence suggests that groups are inefficient at providing threshold public goods. This inefficiency appears to reflect an inability to coordinate over how to distribute the cost of providing the good. So, why do groups not just split the cost equally? We offer an answer to this question by demonstrating that in a standard threshold public good game there is no collectively rational recommendation. We also demonstrate that if full agreement is required in order to provide the public good then there is a collectively rational recommendation, namely, to split the cost equally. Requiring full agreement may, therefore, increase efficiency in providing threshold public goods. We test this hypothesis experimentally and find support for it