Estimating HIV Medication Adherence and Persistence: Two Instruments for Clinical and Research Use

Antiretroviral therapy (ART) requires lifelong daily oral therapy. While patient characteristics associated with suboptimal ART adherence and persistence have been described in cohorts of HIV-infected persons, these factors are poor predictors of individual medication taking behaviors. We aimed to create and test instruments for the estimation of future ART adherence and persistence for clinical and research applications. Following formative work, a battery of 148 items broadly related to HIV infection and treatment was developed and administered to 181 HIV-infected patients. ART adherence and persistence were assessed using electronic monitoring for 3 months. Perceived confidence in medication taking and self-reported barriers to adherence were strongest in predicting non-adherence over time. Barriers to adherence (e.g., affordability, scheduling) were the strongest predictors of non-adherence, as well as 3- and 7-day non-persistence. A ten-item battery for prediction of these outcomes (www.med.unc.edu/ncaidstraining/adherence/for-providers) and a 30-item battery reflective of underlying psychological constructs can help identify and study individuals at risk for suboptimal ART adherence and persistence

Synthesis and binding studies of novel sigma receptor ligands

Abstract only availableSigma receptors are binding sites that are found in the brain, in the endocrine and immune systems, and also in the lungs, kidneys, intestines, muscles and especially the liver. They are classified into two subtypes, sigma1 and sigma2, both of which have unique characteristics. Sigma receptors in the central nervous system are thought to be involved in disorders such as psychoses, Alzheimer's disease, and schizophrenia. A number of human tumors also show high densities of sigma receptors. In this study, three novel compounds were synthesized with the intent of characterizing how their structural differences affect affinity for the sigma1 and sigma2 receptors. We investigated derivatives of a potent sigma1 selective agonist, 1-(3',4'-dimethoxyphenethyl)-4-(3''-phenyl propyl)piperazine, developed by Santen Pharmaceutical Co. Specifically, the 4'-methoxy moiety was replaced by benzyloxy, phenethyloxy and 3-phenylpropyloxy substituents. These were prepared by reaction of the corresponding 4'-phenol with base and treatment with phenethyl bromide, 3-phenylpropyl bromide or benzyl bromide. For the phenethyl and 3-phenylpropyl derivatives, a mixture of 40% KOH and tetrabutylammonium hydroxide (1M in MeOH) was used as the base. Column chromatography provided these target compounds in 81 - 94% purified yields. The benzyl derivative proved difficult to obtain using this procedure, and different conditions were used to synthesize this compound. The 4'-phenol was reacted with benzyl bromide and potassium carbonate in ethanol to give the benzyl ether in 35% yield after purification by column chromatography. All three compounds were characterized by 1H NMR, and were analyzed by elemental analysis and HPLC. Currently, competition receptor binding studies are being run on the synthesized compounds to measure their affinities for sigma1 and sigma2 receptors.NSF-REU/NIH Program in Radiochemistr

Financial Incentives for Adherence to Hepatitis C Virus Clinical Care and Treatment: A Randomized Trial of Two Strategies

Although rates of sustained virologic response (SVR) after hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) surpass 90% in trials and some more “real world” settings, some patients, such as those with substance use disorders, will be challenged to adhere to HCV care

Cervicovaginal and Rectal Fluid as a Surrogate Marker of Antiretroviral Tissue Concentration: Implications for Clinical Trial Design

Quantifying tissue drug concentrations can yield important information during drug development, but complicates pharmacokinetic study design. Mucosal fluids collected by direct aspiration(cervicovaginal fluid; CVF) or swab(rectal fluid; RF) might be used as tissue concentration surrogates, but these relationships are not well characterized

Hierarchy Theory of Evolution and the Extended Evolutionary Synthesis: Some Epistemic Bridges, Some Conceptual Rifts

Contemporary evolutionary biology comprises a plural landscape of multiple co-existent conceptual frameworks and strenuous voices that disagree on the nature and scope of evolutionary theory. Since the mid-eighties, some of these conceptual frameworks have denounced the ontologies of the Modern Synthesis and of the updated Standard Theory of Evolution as unfinished or even flawed. In this paper, we analyze and compare two of those conceptual frameworks, namely Niles Eldredge’s Hierarchy Theory of Evolution (with its extended ontology of evolutionary entities) and the Extended Evolutionary Synthesis (with its proposal of an extended ontology of evolutionary processes), in an attempt to map some epistemic bridges (e.g. compatible views of causation; niche construction) and some conceptual rifts (e.g. extra-genetic inheritance; different perspectives on macroevolution; contrasting standpoints held in the “externalism–internalism” debate) that exist between them. This paper seeks to encourage theoretical, philosophical and historiographical discussions about pluralism or the possible unification of contemporary evolutionary biology

Evidence for Nearby Supernova Explosions

Supernova explosions are one of the most energetic--and potentially lethal--phenomena in the Universe. Scientists have speculated for decades about the possible consequences for life on Earth of a nearby supernova, but plausible candidates for such an event were lacking. Here we show that the Scorpius-Centaurus OB association, a group of young stars currently located at~130 parsecs from the Sun, has generated 20 SN explosions during the last 11 Myr, some of them probably as close as 40 pc to our planet. We find that the deposition on Earth of 60Fe atoms produced by these explosions can explain the recent measurements of an excess of this isotope in deep ocean crust samples. We propose that ~2 Myr ago, one of the SNe exploded close enough to Earth to seriously damage the ozone layer, provoking or contributing to the Pliocene-Pleistocene boundary marine extinction.Comment: 4 pages, 2 figures. Replaced by final version to appear in Physical Review Letter

Global cooling as a driver of diversification in a major marine clade

Climate is a strong driver of global diversity and will become increasingly important as human influences drive temperature changes at unprecedented rates. Here we investigate diversification and speciation trends within a diverse group of aquatic crustaceans, the Anomura. We use a phylogenetic framework to demonstrate that speciation rate is correlated with global cooling across the entire tree, in contrast to previous studies. Additionally, we find that marine clades continue to show evidence of increased speciation rates with cooler global temperatures, while the single freshwater clade shows the opposite trend with speciation rates positively correlated to global warming. Our findings suggest that both global cooling and warming lead to diversification and that habitat plays a role in the responses of species to climate change. These results have important implications for our understanding of how extant biota respond to ongoing climate change and are of particular importance for conservation planning of marine ecosystems