Field of genes: the politics of science and identity in the Estonian genome project

This case study of the Estonian Genome Project (EGP) analyses the Estonian policy decision to construct a national human gene bank. Drawing upon qualitative data from newspaper articles and public policy documents, it focuses on how proponents use discourse to link the EGP to the broader political goal of securing Estonia's position within the Western/European scientific and cultural space. This dominant narrative is then situated within the analytical notion of the “brand state”, which raises potentially negative political consequences for this type of market‐driven genomic research. Considered against the increasing number of countries engaging in gene bank and/or gene database projects, this analysis of Estonia elucidates issues that cross national boundaries, while also illuminating factors specific to this small, post‐Soviet state as it enters the global biocybernetic economy.     

Programmatic Cost Evaluation of Nontargeted Opt-Out Rapid HIV Screening in the Emergency Department

Background

The Centers for Disease Control and Prevention recommends nontargeted opt-out HIV screening in healthcare settings. Cost effectiveness is critical when considering potential screening methods. Our goal was to compare programmatic costs of nontargeted opt-out rapid HIV screening with physician-directed diagnostic rapid HIV testing in an urban emergency department (ED) as part of the Denver ED HIV Opt-Out Trial.

Methods

This was a prospective cohort study nested in a larger quasi-experiment. Over 16 months, nontargeted rapid HIV screening (intervention) and diagnostic rapid HIV testing (control) were alternated in 4-month time blocks. During the intervention phase, patients were offered HIV testing using an opt-out approach during registration; during the control phase, physicians used a diagnostic approach to offer HIV testing to patients. Each method was fully integrated into ED operations. Direct program costs were determined using the perspective of the ED. Time-motion methodology was used to estimate personnel activity costs. Costs per patient newly-diagnosed with HIV infection by intervention phase, and incremental cost effectiveness ratios were calculated.

Results

During the intervention phase, 28,043 eligible patients were included, 6,933 (25%) completed testing, and 15 (0.2%, 95% CI: 0.1%–0.4%) were newly-diagnosed with HIV infection. During the control phase, 29,925 eligible patients were included, 243 (0.8%) completed testing, and 4 (1.7%, 95% CI: 0.4%–4.2%) were newly-diagnosed with HIV infection. Total annualized costs for nontargeted screening were $148,997, whereas total annualized costs for diagnostic HIV testing were $31,355. The average costs per HIV diagnosis were $9,932 and $7,839, respectively. Nontargeted HIV screening identified 11 more HIV infections at an incremental cost of $10,693 per additional infection.

Conclusions

Compared to diagnostic testing, nontargeted HIV screening was more costly but identified more HIV infections. More effective and less costly testing strategies may be required to improve the identification of patients with undiagnosed HIV infection in the ED.     

Sex Differences and Emotion Regulation: An Event-Related Potential Study

Difficulties in emotion regulation have been implicated as a potential mechanism underlying anxiety and mood disorders. It is possible that sex differences in emotion regulation may contribute towards the heightened female prevalence for these disorders. Previous fMRI studies of sex differences in emotion regulation have shown mixed results, possibly due to difficulties in discriminating the component processes of early emotional reactivity and emotion regulation. The present study used event-related potentials (ERPs) to examine sex differences in N1 and N2 components (reflecting early emotional reactivity) and P3 and LPP components (reflecting emotion regulation). N1, N2, P3, and LPP were recorded from 20 men and 23 women who were instructed to “increase,” “decrease,” and “maintain” their emotional response during passive viewing of negative images. Results indicated that women had significantly greater N1 and N2 amplitudes (reflecting early emotional reactivity) to negative stimuli than men, supporting a female negativity bias. LPP amplitudes increased to the “increase” instruction, and women displayed greater LPP amplitudes than men to the “increase” instruction. There were no differences to the “decrease” instruction in women or men. These findings confirm predictions of the female negativity bias hypothesis and suggest that women have greater up-regulation of emotional responses to negative stimuli. This finding is highly significant in light of the female vulnerability for developing anxiety disorders.     

An IDEA for Short Term Outbreak Projection: Nearcasting Using the Basic Reproduction Number

Background

Communicable disease outbreaks of novel or existing pathogens threaten human health around the globe. It would be desirable to rapidly characterize such outbreaks and develop accurate projections of their duration and cumulative size even when limited preliminary data are available. Here we develop a mathematical model to aid public health authorities in tracking the expansion and contraction of outbreaks with explicit representation of factors (other than population immunity) that may slow epidemic growth.

Methodology

The Incidence Decay and Exponential Adjustment (IDEA) model is a parsimonious function that uses the basic reproduction number R₀, along with a discounting factor to project the growth of outbreaks using only basic epidemiological information (e.g., daily incidence counts).

Principal Findings

Compared to simulated data, IDEA provides highly accurate estimates of total size and duration for a given outbreak when R₀ is low or moderate, and also identifies turning points or new waves. When tested with an outbreak of pandemic influenza A (H1N1), the model generates estimated incidence at the i+1^th serial interval using data from the i^th serial interval within an average of 20% of actual incidence.

Conclusions and Significance

This model for communicable disease outbreaks provides rapid assessments of outbreak growth and public health interventions. Further evaluation in the context of real-world outbreaks will establish the utility of IDEA as a tool for front-line epidemiologists.     

Characterization of a New Chronic Lymphocytic Leukemia Cell Line for Mechanistic In Vitro and In Vivo Studies Relevant to Disease

Studies of chronic lymphocytic leukemia (CLL) have yielded substantial progress, however a lack of immortalized cell lines representative of the primary disease has hampered a full understanding of disease pathogenesis and development of new treatments. Here we describe a novel CLL cell line (OSU-CLL) generated by EBV transformation, which displays a similar cytogenetic and immunophenotype observed in the patient’s CLL (CD5 positive with trisomy 12 and 19). A companion cell line was also generated from the same patient (OSU-NB). This cell line lacked typical CLL characteristics, and is likely derived from the patient’s normal B cells. In vitro migration assays demonstrated that OSU-CLL exhibits migratory properties similar to primary CLL cells whereas OSU-NB has significantly reduced ability to migrate spontaneously or towards chemokine. Microarray analysis demonstrated distinct gene expression patterns in the two cell lines, including genes on chromosomes 12 and 19, which is consistent with the cytogenetic profile in this cell line. Finally, OSU-CLL was readily transplantable into NOG mice, producing uniform engraftment by three weeks with leukemic cells detectable in the peripheral blood spleen and bone marrow. These studies describe a new CLL cell line that extends currently available models to study gene function in this disease.     

Presynaptic to postsynaptic relationships of the neuromuscular junction are held constant across age and muscle fiber type

The neuromuscular junction (NMJ) displays considerable morphological plasticity as a result of differences in activity level, as well as aging. This is true of both presynaptic and postsynaptic components of the NMJ. Yet, despite these variations in NMJ structure, proper presynaptic to postsynaptic coupling must be maintained in order for effective cell‐to‐cell communication to occur. Here, we examined the NMJs of muscles with different activity profiles (soleus and EDL), on both slow‐ and fast‐twitch fibers in those muscles, and among young adult and aged animals. We used immunofluorescent techniques to stain nerve terminal branching, presynaptic vesicles, postsynaptic receptors, as well as fast/slow myosin heavy chain. Confocal microscopy was used to capture images of NMJs for later quantitative analysis. Data were subjected to a two‐way ANOVA (main effects for myofiber type and age), and in the event of a significant (p < 0.05) F ratio, a post hoc analysis was performed to identify pairwise differences. Results showed that the NMJs of different myofiber types routinely displayed differences in presynaptic and postsynaptic morphology (although the effect on NMJ size was reversed in the soleus and the EDL), but presynaptic to postsynaptic relationships were tightly maintained. Moreover, the ratio of presynaptic vesicles relative to nerve terminal branch length also was similar despite differences in muscles, their fiber type, and age. Thus, in the face of considerable overall structural differences of the NMJ, presynaptic to postsynaptic coupling remains constant, as does the relationship between presynaptic vesicles and the nerve terminal branches that support them. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 744–753, 2013     

Minimal Erythema Dose (MED) Testing

Ultraviolet radiation (UV) therapy is sometimes used as a treatment for various common skin conditions, including psoriasis, acne, and eczema. The dosage of UV light is prescribed according to an individual''s skin sensitivity. Thus, to establish the proper dosage of UV light to administer to a patient, the patient is sometimes screened to determine a minimal erythema dose (MED), which is the amount of UV radiation that will produce minimal erythema (sunburn or redness caused by engorgement of capillaries) of an individual''s skin within a few hours following exposure. This article describes how to conduct minimal erythema dose (MED) testing. There is currently no easy way to determine an appropriate UV dose for clinical or research purposes without conducting formal MED testing, requiring observation hours after testing, or informal trial and error testing with the risks of under- or over-dosing. However, some alternative methods are discussed.     

Underestimating Calorie Content When Healthy Foods Are Present: An Averaging Effect or a Reference-Dependent Anchoring Effect?

Objective

Previous studies have shown that estimations of the calorie content of an unhealthy main meal food tend to be lower when the food is shown alongside a healthy item (e.g. fruit or vegetables) than when shown alone. This effect has been called the negative calorie illusion and has been attributed to averaging the unhealthy (vice) and healthy (virtue) foods leading to increased perceived healthiness and reduced calorie estimates. The current study aimed to replicate and extend these findings to test the hypothesized mediating effect of ratings of healthiness of foods on calorie estimates.

Methods

In three online studies, participants were invited to make calorie estimates of combinations of foods. Healthiness ratings of the food were also assessed.

Results

The first two studies failed to replicate the negative calorie illusion. In a final study, the use of a reference food, closely following a procedure from a previously published study, did elicit a negative calorie illusion. No evidence was found for a mediating role of healthiness estimates.

Conclusion

The negative calorie illusion appears to be a function of the contrast between a food being judged and a reference, supporting the hypothesis that the negative calorie illusion arises from the use of a reference-dependent anchoring and adjustment heuristic and not from an ‘averaging’ effect, as initially proposed. This finding is consistent with existing data on sequential calorie estimates, and highlights a significant impact of the order in which foods are viewed on how foods are evaluated.