Monitoring Temporal Changes in the Specificity of an Oral HIV Test: A Novel Application for Use in Postmarketing Surveillance

BACKGROUND: Postmarketing surveillance is routinely conducted to monitor performance of pharmaceuticals and testing devices in the marketplace. However, these surveillance methods are often done retrospectively and, as a result, are not designed to detect issues with performance in real-time. METHODS AND FINDINGS: Using HIV antibody screening test data from New York City STD clinics, we developed a formal, statistical method of prospectively detecting temporal clusters of poor performance of a screening test. From 2005 to 2008, New York City, as well as other states, observed unexpectedly high false-positive (FP) rates in an oral fluid-based rapid test used for screening HIV. We attempted to formally assess whether the performance of this HIV screening test statistically deviated from both local expectation and the manufacturer's claim for the test. Results indicate that there were two significant temporal clusters in the FP rate of the oral HIV test, both of which exceeded the manufacturer's upper limit of the 95% CI for the product. Furthermore, the FP rate of the test varied significantly by both STD clinic and test lot, though not by test operator. CONCLUSIONS: Continuous monitoring of surveillance data has the benefit of providing information regarding test performance, and if conducted in real-time, it can enable programs to examine reasons for poor test performance in close proximity to the occurrence. Techniques used in this study could be a valuable addition for postmarketing surveillance of test performance and may become particularly important with the increase in rapid testing methods

dTip60 HAT Activity Controls Synaptic Bouton Expansion at the Drosophila Neuromuscular Junction

Background: Histone acetylation of chromatin plays a key role in promoting the dynamic transcriptional responses in neurons that influence the neuroplasticity linked to cognitive ability, yet the specific histone acetyltransferases (HATs) that create such epigenetic marks remain to be elucidated. Methods and Findings: Here we use the Drosophila neuromuscular junction (NMJ) as a well-characterized synapse model to identify HATs that control synaptic remodeling and structure. We show that the HAT dTip60 is concentrated both pre and post-synaptically within the NMJ. Presynaptic targeted reduction of dTip60 HAT activity causes a significant increase in synaptic bouton number that specifically affects type Is boutons. The excess boutons show a suppression of the active zone synaptic function marker bruchpilot, suggesting defects in neurotransmission function. Analysis of microtubule organization within these excess boutons using immunohistochemical staining to the microtubule associated protein futsch reveals a significant increase in the rearrangement of microtubule loop architecture that is required for bouton division. Moreover, a-tubulin acetylation levels of microtubules specifically extending into the terminal synaptic boutons are reduced in response to dTip60 HAT reduction. Conclusions: Our results are the first to demonstrate a causative role for the HAT dTip60 in the control of synaptic plasticity that is achieved, at least in part, via regulation of the synaptic microtubule cytoskeleton. These findings have implication

Prepregnancy overweight and obesity as risk factors for birth defects: a cross-sectional study over a 30-year period

Overweight and obesity are public health problems worldwide despite being modifiable conditions. The association between birth defects and pregestational maternal body mass index is not entirely clear. We aimed to assess the prevalence and estimate the risk of birth defects related to pregestational body mass index and other maternal factors. We explored a 30-year time series database in a cross-section study. We analysed 40,217 cases, among them 2.8% had birth defects. Bivariate analysis showed a higher prevalence of birth defects with increased pre-pregnancy body mass index and in extremes of maternal age, white skin colour, and primiparity. Multivariable logistic regression showed a higher chance of birth defects in women with pre-pregnancy overweight/obesity (OR:1.19 [CI95%:1.01–1.41]), maternal age ≥ 40 years (OR:1.68 [CI95%:1.11–2.54]), and white skin colour (OR:1.44 [CI95%:1.19–1.75]). Maternal weight is a modifiable risk factor that must be considered and addressed in preconception counselling to minimise possible deleterious effects on embryogenesis.IMPACT STATEMENT What is already known on this subject? Previous studies have linked some maternal factors with birth defects. However, the association with prepregnancy maternal body mass index is not clear. What do the results of this study add? Our findings provide support for the association of prepregnancy maternal overweight and obesity with birth defects and highlight that BMI is a modified risk factor. What are the implications of these findings for clinical practice and/or further research? Maternal body mass index is a modifiable risk factor, highlighting the importance of preconception counselling for the prevention and possible reduction of factors that increase the risk of birth defects

Clinic-level temporal signals of the daily false positive rate of the Orasure rapid oral HIV test performed in New York City's 10 DOHMH STD clinics from March 1^st 2005 to June 30^th 2008.

<p>Showing clinic-level signals with a p-value of less than 0.01 only.</p

Using STD Electronic Medical Record Data to Drive Public Health Program Decisions in New York City

Electronic medical records can house patient information gathered over time and at multiple sites, thus they have the potential to increase continuity of care and improve service delivery in a multiclinic system