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

Improving Photometric Redshifts using GALEX Observations for the SDSS Stripe 82 and the Next Generation of SZ Cluster Surveys

Four large-area Sunyaev-Zeldovich (SZ) experiments -- APEX-SZ, SPT, ACT, and Planck -- promise to detect clusters of galaxies through the distortion of Cosmic Microwave Background photons by hot (> 10^6 K) cluster gas (the SZ effect) over thousands of square degrees. A large observational follow-up effort to obtain redshifts for these SZ-detected clusters is under way. Given the large area covered by these surveys, most of the redshifts will be obtained via the photometric redshift (photo-z) technique. Here we demonstrate, in an application using ~3000 SDSS stripe 82 galaxies with r<20, how the addition of GALEX photometry (FUV, NUV) greatly improves the photometric redshifts of galaxies obtained with optical griz or ugriz photometry. In the case where large spectroscopic training sets are available, empirical neural-network-based techniques (e.g., ANNz) can yield a photo-z scatter of $\sigma_z = 0.018 (1+z)$. If large spectroscopic training sets are not available, the addition of GALEX data makes possible the use simple maximum likelihood techniques, without resorting to Bayesian priors, and obtains $\sigma_z=0.04(1+z)$, accuracy that approaches the accuracy obtained using spectroscopic training of neural networks on ugriz observations. This improvement is especially notable for blue galaxies. To achieve these results, we have developed a new set of high resolution spectral templates based on physical information about the star formation history of galaxies. We envision these templates to be useful for the next generation of photo-z applications. We make our spectral templates and new photo-z catalogs available to the community at http://www.ice.csic.es/personal/jimenez/PHOTOZ .Comment: 10 pages, 8 figure

Linking haloes to galaxies: how many halo properties are needed?

Recent studies emphasize that an empirical relation between the stellar mass of galaxies and the mass of their host dark matter subhaloes can predict the clustering of galaxies and its evolution with cosmic time. In this paper we study the assumptions made by this methodology using a semi-analytical model (SAM). To this end, we randomly swap between the locations of model galaxies within a narrow range of subhalo mass (M_infall). We find that shuffled samples of galaxies have different auto-correlation functions in comparison with the original model galaxies. This difference is significant even if central and satellite galaxies are allowed to follow a different relation between M_infall and stellar mass, and can reach a factor of 2 for massive galaxies at redshift zero. We analyze three features within SAMs that contribute to this effect: a) The relation between stellar mass and subhalo mass evolves with redshift for central galaxies, affecting satellite galaxies at the time of infall. b) The stellar mass of galaxies falling into groups and clusters at high redshift is different from the mass of central galaxies at the same time. c) The stellar mass growth for satellite galaxies after infall can be significant and depends on the infall redshift and the group mass. We show that the above is true for differing SAMs, and that the effect is sensitive to the treatment of dynamical friction and stripping of gas in satellite galaxies. We find that by using the FoF group mass at redshift zero in addition to M_infall, an empirical model is able to accurately reproduce the clustering properties of galaxies. On the other hand, using the infall redshift as a second parameter does not yield as good results because it is less correlated with stellar mass. Our analysis indicates that environmental processes are important for modeling the clustering and abundance of galaxies. (Abridged)Comment: Accepted for publication in MNRAS, minor changes from version

Gene Expression Changes Related to Endocrine Function and Decline in Reproduction in Fathead Minnow (Pimephales promelas) after Dietary Methylmercury Exposure

BACKGROUND: Methylmercury (MeHg) is a known neurotoxic agent, but the mechanisms by which MeHg may act on reproductive pathways are relatively unknown. Several studies have indicated potential changes in hormone levels as well as declines in vertebrates with increasing dietary MeHg exposure. OBJECTIVES: The purpose of this study was to identify alterations in gene expression associated with MeHg exposure, specifically those associated with previously observed changes in reproduction and reproductive biomarkers. Fathead minnows, Pimephales promelas, were fed one of three diets that were similar to documented concentrations of MeHg in the diets of wild invertivorous and piscivorous fish. We used a commercial macroarray in conjunction with quantitative polymerase chain reaction to examine gene expression in fish in relation to exposure to these environmentally relevant doses of MeHg. RESULTS: Expression of genes commonly associated with endocrine disruption was altered with Hg exposure. Specifically, we observed a marked up-regulation in vitellogenin mRNA in individual Hg-exposed males and a significant decline in vitellogenin gene expression in female fish with increasing Hg concentrations. Other genes identified by the macroarray experiment included those associated with egg fertilization and development, sugar metabolism, apoptosis, and electron transport. We also observed differences in expression patterns between male and female fish not related to genes specifically associated with reproduction, indicating a potential physiological difference in the reaction of males and females to MeHg. CONCLUSION: Gene expression data may provide insight into the mechanisms by which MeHg affects reproduction in fish and indicate how MeHg differs in its effect from other heavy metals and endocrine-disrupting compounds

PITX2 Modulates Atrial Membrane Potential and the Antiarrhythmic Effects of Sodium-Channel Blockers.

BACKGROUND: Antiarrhythmic drugs are widely used to treat patients with atrial fibrillation (AF), but the mechanisms conveying their variable effectiveness are not known. Recent data suggested that paired like homeodomain-2 transcription factor (PITX2) might play an important role in regulating gene expression and electrical function of the adult left atrium (LA). OBJECTIVES: After determining LA PITX2 expression in AF patients requiring rhythm control therapy, the authors assessed the effects of Pitx2c on LA electrophysiology and the effect of antiarrhythmic drugs. METHODS: LA PITX2 messenger ribonucleic acid (mRNA) levels were measured in 95 patients undergoing thoracoscopic AF ablation. The effects of flecainide, a sodium (Na(+))-channel blocker, and d,l-sotalol, a potassium channel blocker, were studied in littermate mice with normal and reduced Pitx2c mRNA by electrophysiological study, optical mapping, and patch clamp studies. PITX2-dependent mechanisms of antiarrhythmic drug action were studied in human embryonic kidney (HEK) cells expressing human Na channels and by modeling human action potentials. RESULTS: Flecainide 1 μmol/l was more effective in suppressing atrial arrhythmias in atria with reduced Pitx2c mRNA levels (Pitx2c(+/-)). Resting membrane potential was more depolarized in Pitx2c(+/-) atria, and TWIK-related acid-sensitive K(+) channel 2 (TASK-2) gene and protein expression were decreased. This resulted in enhanced post-repolarization refractoriness and more effective Na-channel inhibition. Defined holding potentials eliminated differences in flecainide's effects between wild-type and Pitx2c(+/-) atrial cardiomyocytes. More positive holding potentials replicated the increased effectiveness of flecainide in blocking human Nav1.5 channels in HEK293 cells. Computer modeling reproduced an enhanced effectiveness of Na-channel block when resting membrane potential was slightly depolarized. CONCLUSIONS: PITX2 mRNA modulates atrial resting membrane potential and thereby alters the effectiveness of Na-channel blockers. PITX2 and ion channels regulating the resting membrane potential may provide novel targets for antiarrhythmic drug development and companion therapeutics in AF

Revisiting the origin of the high metallicities of sub-damped Lyman-alpha systems

Sub-damped Lyman-alpha systems (sub-DLAs) have previously been found to exhibit a steeper metallicity evolution than the classical damped Lyman-alpha systems (DLAs), evolving to close to solar metallicity by z~1. From new high-resolution spectra of 17 sub-DLAs we have increased the number of measurements of [Fe/H] at z<1.7 by 25% and compiled the most complete literature sample of sub-DLA and DLA abundances to date. We find that sub-DLAs are indeed significantly more metal-rich than DLAs, but only at z<1.7; the metallicity distributions of sub-DLAs and DLAs at z>1.7 are statistically consistent. We also present the first evidence that sub-DLAs follow a velocity width-metallicity correlation over the same velocity range as DLAs, but the relation is offset to higher metallicities than the DLA relation. On the basis of these results, we revisit the previous explanation that the systematically higher metallicities observed in sub-DLAs are indicative of higher host galaxy masses. We discuss the various problems that this interpretation encounters and conclude that in general sub-DLAs are not uniquely synonymous with massive galaxies. We rule out physically related sources of bias (dust, environment, ionization effects) and examine systematics associated with the selection and analysis of low-redshift sub-DLAs. We propose that the high metallicities of sub-DLAs at z<1.7 that drives an apparently steep evolution may be due to the selection of most low-redshift sub-DLAs based on their high MgII equivalent widths.Comment: 6 pages, 3 figures, MNRAS, in pres

Relevance or Excellence? Setting Research Priorities for Mental Health and Psychosocial Support in Humanitarian Settings

Background: Humanitarian crises are associated with an increase in mental disorders and psychological distress. Despite the emerging consensus on intervention strategies in humanitarian settings, the field of mental health and psychosocial support (MHPSS) in humanitarian settings lacks a consensus-based research agenda. Methods: From August 2009 to February 2010, we contacted policymakers, academic researchers, and humanitarian aid workers, and conducted nine semistructured focus group discussions with 114 participants in three locations (Peru, Uganda, and Nepal), in both the capitals and remote humanitarian settings. Local stakeholders representing a range of academic expertise (psychiatry, psychology, social work, child protection, and medical anthropology) and organizations (governments, universities, nongovernmental organizations, and UN agencies) were asked to identify priority questions for MHPSS research in humanitarian settings, and to discuss factors that hamper and facilitate research. Results: Thematic analyses of transcripts show that participants broadly agreed on prioritized research themes in the following order: (1) the prevalence and burden of mental health and psychosocial difficulties in humanitarian settings, (2) how MHPSS implementation can be improved, (3) evaluation of specific MHPSS interventions, (4) the determinants of mental health and psychological distress, and (5) improved research methods and processes. Rather than differences in research themes across countries, what emerged was a disconnect between different groups of stakeholders regarding research processes: the perceived lack of translation of research findings into actual policy and programs; misunderstanding of research methods by aid workers; different appreciation of the time needed to conduct research; and disputed universality of research constructs. Conclusions: To advance a collaborative research agenda, actors in this field need to bridge the perceived disconnect between the goals of “relevance” and “excellence.” Research needs to be more sensitive to questions and concerns arising from humanitarian interventions, and practitioners need to take research findings into account in designing interventions. (Harv Rev Psychiatry 2012;20:25–36.