Experience with daptomycin daily dosing in ICU patients undergoing continuous renal replacement therapy

Purpose: For critically ill patients undergoing continuous renal replacement therapy (CRRT), daptomycin dosing recommendations are scarce. We, therefore, retrospectively assessed routinely measured daptomycin plasma concentrations, daptomycin dose administered and microbiological data in 11 critically ill patients with Gram-positive infections that had received daptomycin once daily. Methods: The retrospective analysis included critically ill patients treated at the intensive care unit (ICU) who had daptomycin plasma concentrations measured. Results: Daptomycin dose ranged from 3 to 8mg/kg/q24h in patients undergoing CRRT (n=7) and 6 to 10mg/kg/q24h in patients without CRRT (n=4). Peak and trough concentrations showed a high intra- and inter-patient variability in both groups, independent of the dosage per kg body weight. No drug accumulation was detected in CRRT patients with once-daily daptomycin dosing. Causative pathogens were Enterococcus faecium (n=6), coagulase-negative Staphylococcus (n=2), Staphylococcus aureus (n=2) and unknown in one patient. Microbiological eradication was successful in 8 of 11 patients. Two of three patients with unsuccessful microbiological eradication and fatal outcome had an Enterococcus faecium infection. Conclusion: In critically ill patients undergoing CRRT, daptomycin exposure with once-daily dosing was similar to ICU patients with normal renal function, but lower compared to healthy volunteers. Our data suggest that daptomycin once-daily dosing is appropriate in patients undergoing CRR

Monitoring and Pay: An Experiment on Employee Performance under Endogenous Supervision

We present an experimental test of a shirking model where monitoring intensity is endogenous and effort a continuous variable. Wage level, monitoring intensity and consequently the desired enforceable effort level are jointly determined by the maximization problem of the firm. As a result, monitoring and pay should be complements. In our experiment, between and within treatment variation is qualitatively in line with the normative predictions of the model under standard assumptions. Yet, we also find evidence for reciprocal behavior. Our data analysis shows, however, that it does not pay for the employer to solely rely on the reciprocity of employees

Pay What You Want as a Marketing Strategy in Monopolistic and Competitive Markets

Pay What You Want (PWYW) can be an attractive marketing strategy to price discriminate between fair-minded and selfish customers, to fully penetrate a market without giving away the product for free, and to undercut competitors that use posted prices. We report on laboratory experiments that identify causal factors determining the willingness of buyers to pay voluntarily under PWYW. Furthermore, to see how competition affects the viability of PWYW, we implement markets in which a PWYW seller competes with a traditional seller. Finally, we endogenize the market structure and let sellers choose their pricing strategy. The experimental results show that outcome-based social preferences and strategic considerations to keep the seller in the market can explain why and how much buyers pay voluntarily to a PWYW seller. We find that PWYW can be viable in isolation, but it is less successful as a competitive strategy because it does not drive traditional posted-price sellers out of the market. Instead, the existence of a posted-price competitor reduces buyers’ payments and prevents the PWYW seller from fully penetrating the market. If given the choice, the majority of sellers opt for setting a posted price rather than a PWYW pricing. We discuss the implications of these results for the use of PWYW as a marketing strategy

Sustainable institutionalized punishment requires elimination of second-order free-riders

Although empirical and theoretical studies affirm that punishment can elevate collaborative efforts, its emergence and stability remain elusive. By peer-punishment the sanctioning is something an individual elects to do depending on the strategies in its neighborhood. The consequences of unsustainable efforts are therefore local. By pool-punishment, on the other hand, where resources for sanctioning are committed in advance and at large, the notion of sustainability has greater significance. In a population with free-riders, punishers must be strong in numbers to keep the "punishment pool" from emptying. Failure to do so renders the concept of institutionalized sanctioning futile. We show that pool-punishment in structured populations is sustainable, but only if second-order free-riders are sanctioned as well, and to a such degree that they cannot prevail. A discontinuous phase transition leads to an outbreak of sustainability when punishers subvert second-order free-riders in the competition against defectors.Comment: 7 two-column pages, 3 figures; accepted for publication in Scientific Report

Spatial prisoner's dilemma game with volunteering in Newman-Watts small-world networks

A modified spatial prisoner's dilemma game with voluntary participation in Newman-Watts small-world networks is studied. Some reasonable ingredients are introduced to the game evolutionary dynamics: each agent in the network is a pure strategist and can only take one of three strategies (\emph {cooperator}, \emph {defector}, and \emph {loner}); its strategical transformation is associated with both the number of strategical states and the magnitude of average profits, which are adopted and acquired by its coplayers in the previous round of play; a stochastic strategy mutation is applied when it gets into the trouble of \emph {local commons} that the agent and its neighbors are in the same state and get the same average payoffs. In the case of very low temptation to defect, it is found that agents are willing to participate in the game in typical small-world region and intensive collective oscillations arise in more random region.Comment: 4 pages, 5 figure

A stringent preemptive protocol reduces cytomegalovirus disease in the first 6 months after kidney transplantation

Background: The optimal strategy to prevent cytomegalovirus (CMV) disease after kidney transplantation continues to be open to debate. The preemptive approach requires regular determination of CMV viremia and prompt initiation of therapy. Methods: We retrospectively compared the incidence of CMV disease during two periods at our center: A first phase (P1, n=84 kidney recipients), during which time the intensity of surveillance was determined by the responsible physician, was compared to a second phase (P2, n=74), when a stringent protocol of CMV surveillance was required for all patients. The preemptive approach was applied for all CMV risk groups; prophylaxis was optional in the case of treatment for rejection or delayed graft function in the intermediate- and high-risk group. Follow-up was truncated at 6months after transplant surgery. CMV syndrome was differentiated from asymptomatic replication by the presence of at least one systemic symptom, while diagnosis of CMV end-organ disease required histological confirmation. Results: Immunosuppression was similar in the two periods. CMV prophylaxis was used equally (26%) in both periods. The probability for asymptomatic viremia episodes was not different for patients in P1 and P2 regardless of the prevention strategy. For patients following the preemptive strategy, the probability for CMV disease was increased during P1 (p=0.016), despite fewer PCR assays being performed in phase 2. Protocol violations were only observed during P1. Conclusions: The probability of CMV disease episodes (CMV syndrome and CMV end-organ disease) was substantially reduced using a very stringent protocol. This study highlights the crucial importance of a stringent protocol with optimal adherence by all caregivers if the preemptive strategy is to be successfu

Evolutionary prisoner's dilemma game with dynamic preferential selection

We study a modified prisoner's dilemma game taking place on two-dimensional disordered square lattices. The players are pure strategists and can either cooperate or defect with their immediate neighbors. In the generations each player update its strategy by following one of the neighboring strategies with a probability dependent on the payoff difference. The neighbor selection obeys a dynamic preferential rule, i.e., the more frequently a neighbor's strategy was adopted by the focal player in the previous rounds, the larger probability it will be chosen to refer to in the subsequent rounds. It is found that cooperation is substantially promoted due to this simple selection mechanism. Corresponding analysis is provided by the investigations of the distribution of players' impact weights, persistence, and as well as correlation function.Comment: 7 pages, 5 figure

Experimental and computational analyses reveal that environmental restrictions shape HIV-1 spread in 3D cultures

Here, using an integrative experimental and computational approach, Imle et al. show how cell motility and density affect HIV cell-associated transmission in a three-dimensional tissue-like culture system of CD4+ T cells and collagen, and how different collagen matrices restrict infection by cell-free virions