Economic Foundations of Cost Effective Analysis

In order to address several controversies in the application of cost-effectiveness analysis, we investigate the principles underlying the technique and discuss the implications for the evaluation of medical interventions. Using a standard von Neumann-Morgenstern utility framework, we show how a cost-effectiveness criterion can be derived to guide resource allocation decisions. We investigate its relation to age, gender, income level, and risk aversion. Cost-effectiveness analysis can be a useful and powerful tool for resource allocation decisions, but in the presence of heterogeneous preferences and personal characteristics, a cost-effectiveness criterion that is applied at the population level is unlikely to yield pareto-optimal resource allocations.

Affective, Behavioral, and Social-Cognitive Dysregulation as Mechanisms for Sexual Abuse Revictimization

Using a sample of 1,117 female college students, this study examined emotional, behavioral, and social-cognitive mechanisms of sexual abuse revictimization. It was hypothesized that numbing, alexithymia, alcohol problems, mistrust, and adult attachment dimensions would mediate the relationship between childhood sexual abuse (CSA) and adult sexual abuse (ASA). Aside from the close adult attachment dimension, the results indicated that all of the hypothesized mediators were associated with CSA. However, only alcohol problems and mistrust met the necessary conditions of mediation. The results with respect to mistrust are especially unique in that it is one of the first empirical demonstrations of a social-cognitive mechanism for sexual abuse revictimization. Thus, these results enhance our understanding of interpersonal mediators of the relationship between CSA and ASA and provide a new direction for future research

A qualitative study exploring the experience of viewing three‐dimensional medical images during an orthopaedic outpatient consultation from the perspective of patients, health care professionals, and lay representatives

Rationale, aims and objectives Three‐dimensional (3D) medical images are shown to patients during clinical consultations about certain health conditions. However, little is known about patients' experience of viewing them. The aim of this qualitative study was to explore the impact of sharing 3D medical images with patients during a clinical consultation about hip surgery, from the perspective of patients, health care professionals, and lay representatives. Method Interviews were conducted with 14 patients who were shown their own 3D medical images during their clinical consultation and four health care professionals conducting consultations within one orthopaedic outpatient clinic. In addition to interviews, 31 lay representatives participated in six focus groups. The focus groups aimed to gain a broader understanding of the advantages and concerns of showing patients their medical images and to compare 3D and two‐dimensional (2D) medical images. Interviews and focus groups were audio‐recorded, transcribed verbatim, and analysed using thematic analysis. Results Three themes were developed from the data: (a) the truthful image, (b) the empowering image, and (c) the unhelpful image. Focus group participants' preference for 3D or 2D images varied between conditions and groups, suggesting that the experience of viewing images may differ between individuals and conditions. Conclusions When shown to patients during an orthopaedic clinical consultation, 3D medical images may be an empowering resource. However, in this study, patients and focus group participants perceived medical images as factual and believed they could provide evidence of a diagnoses. This perception could result in overreliance in imaging tests or disregard for other forms of information

Do medical images aid understanding and recall of medical information? An experimental study comparing the experience of viewing no image, a 2D medical image and a 3D medical image alongside a diagnosis

Objective: This study compared the experience of viewing 3D medical images, 2D medical images and no image presented alongside a diagnosis. Methods: We conducted two laboratory experiments, each with 126 healthy participants. Participants heard three diagnoses; one accompanied by 3D medical images, one accompanied by 2D medical images and one with no image. Participants completed a questionnaire after each diagnosis rating their experience. In Experiment 2, half of the participants were informed that image interpretation can be susceptible to errors. Results: Participants preferred to view 3D images alongside a diagnosis (p < .001) and reported greater understanding (p < .001), perceived accuracy (p < .001) and increased trust (p < .001) when the diagnosis was accompanied by an image compared to no image. There was no significant difference in trust between participants who were informed of errors within image interpretation and those who were not. Conclusion: When presented alongside a diagnosis, medical images may aid patient understanding, recall and trust in medical information. Practical Considerations: Medical images may be a powerful resource for patients that could be utilised by clinicians during consultations

Microbiota alter metabolism and mediate neurodevelopmental toxicity of 17β-estradiol

Estrogenic chemicals are widespread environmental contaminants associated with diverse health and ecological effects. During early vertebrate development, estrogen receptor signaling is critical for many different physiologic responses, including nervous system function. Recently, host-associated microbiota have been shown to influence neurodevelopment. Here, we hypothesized that microbiota may biotransform exogenous 17-βestradiol (E2) and modify E2 effects on swimming behavior. Colonized zebrafish were continuously exposed to non-teratogenic E2 concentrations from 1 to 10 days post-fertilization (dpf). Changes in microbial composition and predicted metagenomic function were evaluated. Locomotor activity was assessed in colonized and axenic (microbe-free) zebrafish exposed to E2 using a standard light/dark behavioral assay. Zebrafish tissue was collected for chemistry analyses. While E2 exposure did not alter microbial composition or putative function, colonized E2-exposed larvae showed reduced locomotor activity in the light, in contrast to axenic E2-exposed larvae, which exhibited normal behavior. Measured E2 concentrations were significantly higher in axenic relative to colonized zebrafish. Integrated peak area for putative sulfonated and glucuronidated E2 metabolites showed a similar trend. These data demonstrate that E2 locomotor effects in the light phase are dependent on the presence of microbiota and suggest that microbiota influence chemical E2 toxicokinetics. More broadly, this work supports the concept that microbial colonization status may influence chemical toxicity

Curved Tails in Polymerization-Based Bacterial Motility

The curved actin ``comet-tail'' of the bacterium Listeria monocytogenes is a visually striking signature of actin polymerization-based motility. Similar actin tails are associated with Shigella flexneri, spotted-fever Rickettsiae, the Vaccinia virus, and vesicles and microspheres in related in vitro systems. We show that the torque required to produce the curvature in the tail can arise from randomly placed actin filaments pushing the bacterium or particle. We find that the curvature magnitude determines the number of actively pushing filaments, independent of viscosity and of the molecular details of force generation. The variation of the curvature with time can be used to infer the dynamics of actin filaments at the bacterial surface.Comment: 8 pages, 2 figures, Latex2

The Structural and Functional Basis for Recurring Sulfa Drug Resistance Mutations in Staphylococcus aureus Dihydropteroate Synthase

Staphylococcal species are a leading cause of bacterial drug-resistant infections and associated mortality. One strategy to combat bacterial drug resistance is to revisit compromised targets, and to circumvent resistance mechanisms using structure-assisted drug discovery. The folate pathway is an ideal candidate for this approach. Antifolates target an essential metabolic pathway, and the necessary detailed structural information is now available for most enzymes in this pathway. Dihydropteroate synthase (DHPS) is the target of the sulfonamide class of drugs, and its well characterized mechanism facilitates detailed analyses of how drug resistance has evolved. Here, we surveyed clinical genetic sequencing data in S. aureus to distinguish natural amino acid variations in DHPS from those that are associated with sulfonamide resistance. Five mutations were identified, F17L, S18L, T51M, E208K, and KE257_dup. Their contribution to resistance and their cost to the catalytic properties of DHPS were evaluated using a combination of biochemical, biophysical and microbiological susceptibility studies. These studies show that F17L, S18L, and T51M directly lead to sulfonamide resistance while unexpectedly increasing susceptibility to trimethoprim, which targets the downstream enzyme dihydrofolate reductase. The secondary mutations E208K and KE257_dup restore trimethoprim susceptibility closer to wild-type levels while further increasing sulfonamide resistance. Structural studies reveal that these mutations appear to selectively disfavor the binding of the sulfonamides by sterically blocking an outer ring moiety that is not present in the substrate. This emphasizes that new inhibitors must be designed that strictly stay within the substrate volume in the context of the transition state