Biology subjects

Murphy, G.

Publications and source records attributed to Murphy, G..

3 recordsLinked to original sources

bioRxiv2018

Interpreting Diagnostic Histories into HIV Infection Time Estimates: Framework and Online Tool

BackgroundIt is frequently of epidemiological and/or clinical interest to estimate the date of HIV infection or time-since-infection of individuals. Yet, for over 15 years, the only widely-referenced infection dating algorithm that utilises diagnostic testing data to estimate time-since-infection has been the Fiebig staging system. This defines a number of stages of early HIV infection through various standard combinations of contemporaneous discordant diagnostic results, using tests of different sensitivity.\n\nObjectiveTo develop a new, more nuanced infection dating algorithm, we generalised the Fiebig approach to accommodate positive and negative diagnostic results generated on the same or different dates, and arbitrary current or future tests - as long as the test sensitivity is known. For this purpose, test sensitivity is conceptualised as the probability that a specimen will produce a positive result, expressed as a function of time since infection. This can be summarised as a median diagnostic delay parameter, together with a measure of inter-subject variability.\n\nMethodsThe present work outlines the analytical framework for infection date estimation using subject-level diagnostic testing histories, and data on test sensitivity. We introduce a publicly-available online HIV infection dating tool that implements this estimation method, bringing together 1) curatorship of HIV test performance data, and 2) infection date estimation functionality, to calculate plausible intervals within which infection likely became detectable for each individual. The midpoints of these intervals are interpreted as infection time point estimates and referred to as Estimated Dates of Detectable Infection (EDDIs).\n\nResultsIn many settings, including most research studies, detailed diagnostic testing data are routinely recorded, and can provide reasonably precise estimates of the timing of HIV infection. We present a simple logic to the interpretation of diagnostic testing histories into infection time estimates, either as a point estimate (EDDI) or an interval (earliest plausible to latest plausible dates of detectable infection), along with a publicly-accessible online tool that supports wide application of this logic.\n\nConclusionsThis tool, available at https://tools.incidence-estimation.org/idt/, is readily updatable as test technology evolves, given the simple architecture of the system and its nature as an open source project.

epidemiology↗

bioRxiv2018

Sparse recurrent excitatory connectivity in the cortical microcircuit of the adult mouse and human

Generating a comprehensive description of cortical networks requires a large-scale, systematic approach. To that end, the Allen Institute is engaged in a pipeline project using multipatch electrophysiology, supplemented with 2-photon optogenetics, to characterize connectivity and synaptic signaling between classes of neurons in adult mouse and human cortex. We focus on producing results detailed enough for the generation of computational models and enabling comparison with future studies. Here we report our examination of intralaminar connectivity within each of several classes of excitatory neurons. We find that connections are sparse but present among all excitatory cell types and layers we sampled, with the most sparse connections in layers 5 and 6. Almost all mouse synapses exhibited short-term depression with similar dynamics. Synaptic signaling between a subset of layer 2/3 neurons; however, exhibited facilitation. These results contribute to a body of evidence describing recurrent excitatory connectivity as a conserved feature of cortical microcircuits.

neuroscience↗

bioRxiv2017

Diagnostic, Infection Timing and Incidence Surveillance Applications of High Dynamic Range Chemiluminescent HIV Immuno-Assay Platforms

BackgroundCustom staging assays, including the Sedia HIV-1 Limiting Antigen Avidity EIA (LAg) and avidity modifications of the Ortho VITROS anti-HIV-1+2 and Abbott ARCHITECT HIV Ag/Ab Combo assays, are used to identify recent infections in clinical settings and for cross-sectional HIV incidence estimation. However, the high dynamic range of chemiluminescent platforms allows differentiating recent and longstanding infection on signal intensity, and this raises the prospect of using unmodified diagnostic assays for infection timing and surveillance applications.\n\nMethodsWe tested a panel of 2,500 well-characterised specimens with estimable duration of HIV infection with the three assays and the unmodified ARCHITECT. Regression models were used to estimate mean durations of recent infection (MDRI), context-specific false-recent rates (FRR) and correlation between signal intensity and LAg measurements. A hypothetical epidemiological scenario was constructed to evaluate utility in surveillance applications.\n\nResultsOver a range of MDRIs (reflecting recency discrimination thresholds), a diluted ARCHITECT-based RITA produced lower FRRs than the VITROS platform (FRR {approx} 0.5% and 1.5% respectively at MDRI of 200 days) and the unmodified diagnostic ARCHITECT produces incidence estimates with comparable precision to LAg (RSE {approx} 17.5% and 15% respectively at MDRI of 200 days). ARCHITECT S/CO measurements were highly correlated with LAg ODn measurements (r = 0.80) and values below 200 are strongly predictive of LAg recency and duration of infection less than one year.\n\nConclusionsLow quantitative measurements from the unmodified ARCHITECT obviate the need for additional recency testing and its use is feasible in clinical staging and incidence surveillance applications.

epidemiology↗