34 research outputs found
A survey of the literature programs in the primary, intermediate, and junior high schools
Thesis (Ed.M.)--Boston UniversityLiterature programs in high schools across the country
The Milky Way Bulge extra-tidal star survey: BH 261 (AL 3)
The Milky Way Bulge extra-tidal star survey (MWBest) is a spectroscopic
survey with the goal of identifying stripped globular cluster stars from inner
Galaxy clusters. In this way, an indication of the fraction of metal-poor bulge
stars that originated from globular clusters can be determined. We observed and
analyzed stars in and around BH 261, an understudied globular cluster in the
bulge. From seven giants within the tidal radius of the cluster, we measured an
average heliocentric radial velocity of = -61 +- 2.6 km/s with a radial
velocity dispersion of \sigma = 6.1 +- 1.9 km/s. The large velocity dispersion
may have arisen from tidal heating in the cluster's orbit about the Galactic
center, or because BH 261 has a high dynamical mass as well as a high
mass-to-light ratio. From spectra of five giants, we measure an average
metallicity of = -1.1 +- 0.2 dex. We also spectroscopically confirm an
RR Lyrae star in BH 261, which yields a distance to the cluster of 7.1 +-
0.4~kpc. Stars with 3D velocities and metallicities consistent with BH 261
reaching to ~0.5 degrees from the cluster are identified. A handful of these
stars are also consistent with the spatial distribution of that potential
debris from models focussing on the most recent disruption of the cluster.Comment: accepted for publication in The Astronomical Journa
Improving Antiretroviral Therapy Adherence in Resource-Limited Settings at Scale: a Discussion of Interventions and Recommendations
INTRODUCTION:
Successful population-level antiretroviral therapy (ART) adherence will be necessary to realize both the clinical and prevention benefits of antiretroviral scale-up and, ultimately, the end of AIDS. Although many people living with HIV are adhering well, others struggle and most are likely to experience challenges in adherence that may threaten virologic suppression at some point during lifelong therapy. Despite the importance of ART adherence, supportive interventions have generally not been implemented at scale. The objective of this review is to summarize the recommendations of clinical, research, and public health experts for scalable ART adherence interventions in resource-limited settings. METHODS:
In July 2015, the Bill and Melinda Gates Foundation convened a meeting to discuss the most promising ART adherence interventions for use at scale in resource-limited settings. This article summarizes that discussion with recent updates. It is not a systematic review, but rather provides practical considerations for programme implementation based on evidence from individual studies, systematic reviews, meta-analyses, and the World Health Organization Consolidated Guidelines for HIV, which include evidence from randomized controlled trials in low- and middle-income countries. Interventions are categorized broadly as education and counselling; information and communication technology-enhanced solutions; healthcare delivery restructuring; and economic incentives and social protection interventions. Each category is discussed, including descriptions of interventions, current evidence for effectiveness, and what appears promising for the near future. Approaches to intervention implementation and impact assessment are then described. RESULTS AND DISCUSSION:
The evidence base is promising for currently available, effective, and scalable ART adherence interventions for resource-limited settings. Numerous interventions build on existing health care infrastructure and leverage available resources. Those most widely studied and implemented to date involve peer counselling, adherence clubs, and short message service (SMS). Many additional interventions could have an important impact on ART adherence with further development, including standardized counselling through multi-media technology, electronic dose monitoring, decentralized and differentiated models of care, and livelihood interventions. Optimal targeting and tailoring of interventions will require improved adherence measurement. CONCLUSION:
The opportunity exists today to address and resolve many of the challenges to effective ART adherence, so that they do not limit the potential of ART to help bring about the end of AIDS
Model-Based Methods to Translate Adolescent Medicine Trials Network for HIV/AIDS Interventions Findings Into Policy Recommendations: Rationale and Protocol for a Modeling Core (ATN 161)
BACKGROUND: The United States Centers for Disease Control and Prevention estimates that approximately 60,000 US youth are living with HIV. US youth living with HIV (YLWH) have poorer outcomes compared with adults, including lower rates of diagnosis, engagement, retention, and virologic suppression. With Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) support, new trials of youth-centered interventions to improve retention in care and medication adherence among YLWH are underway.
OBJECTIVE: This study aimed to use a computer simulation model, the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-Adolescent Model, to evaluate selected ongoing and forthcoming ATN interventions to improve viral load suppression among YLWH and to define the benchmarks for uptake, effectiveness, durability of effect, and cost that will make these interventions clinically beneficial and cost-effective.
METHODS: This protocol, ATN 161, establishes the ATN Modeling Core. The Modeling Core leverages extensive data-already collected by successfully completed National Institutes of Health-supported studies-to develop novel approaches for modeling critical components of HIV disease and care in YLWH. As new data emerge from ongoing ATN trials during the award period about the effectiveness of novel interventions, the CEPAC-Adolescent simulation model will serve as a flexible tool to project their long-term clinical impact and cost-effectiveness. The Modeling Core will derive model input parameters and create a model structure that reflects key aspects of HIV acquisition, progression, and treatment in YLWH. The ATN Modeling Core Steering Committee, with guidance from ATN leadership and scientific experts, will select and prioritize specific model-based analyses as well as provide feedback on derivation of model input parameters and model assumptions. Project-specific teams will help frame research questions for model-based analyses as well as provide feedback regarding project-specific inputs, results, sensitivity analyses, and policy conclusions.
RESULTS: This project was funded as of September 2017.
CONCLUSIONS: The ATN Modeling Core will provide critical information to guide the scale-up of ATN interventions and the translation of ATN data into policy recommendations for YLWH in the United States
Calcium Dynamics of <i>Ex Vivo</i> Long-Term Cultured CD8<sup>+</sup> T Cells Are Regulated by Changes in Redox Metabolism
<div><p>T cells reach a state of replicative senescence characterized by a decreased ability to proliferate and respond to foreign antigens. Calcium release associated with TCR engagement is widely used as a surrogate measure of T cell response. Using an ex vivo culture model that partially replicates features of organismal aging, we observe that while the amplitude of Ca<sup>2+</sup> signaling does not change with time in culture, older T cells exhibit faster Ca<sup>2+</sup> rise and a faster decay. Gene expression analysis of Ca<sup>2+</sup> channels and pumps expressed in T cells by RT-qPCR identified overexpression of the plasma membrane CRAC channel subunit ORAI1 and PMCA in older T cells. To test whether overexpression of the plasma membrane Ca<sup>2+</sup> channel is sufficient to explain the kinetic information, we adapted a previously published computational model by Maurya and Subramaniam to include additional details on the store-operated calcium entry (SOCE) process to recapitulate Ca<sup>2+</sup> dynamics after T cell receptor stimulation. Simulations demonstrated that upregulation of ORAI1 and PMCA channels is not sufficient to explain the observed alterations in Ca<sup>2+</sup> signaling. Instead, modeling analysis identified kinetic parameters associated with the IP<sub>3</sub>R and STIM1 channels as potential causes for alterations in Ca<sup>2+</sup> dynamics associated with the long term ex vivo culturing protocol. Due to these proteins having known cysteine residues susceptible to oxidation, we subsequently investigated and observed transcriptional remodeling of metabolic enzymes, a shift to more oxidized redox couples, and post-translational thiol oxidation of STIM1. The model-directed findings from this study highlight changes in the cellular redox environment that may ultimately lead to altered T cell calcium dynamics during immunosenescence or organismal aging.</p></div
A review of factors to consider when using camera traps to study animal behavior to inform wildlife ecology and conservation
Camera traps (CTs) are an increasingly popular method of studying animal behavior. However, the impact of cameras on detected individualsâsuch as from mechanical noise, odor, and emitted lightâhas received relatively little attention. These impacts are particularly important in behavioral studies in conservation that seek to ascribe changes in behavior to relevant environmental factors. In this article, we discuss three sources of bias that are relevant to conservation behavior studies using CTs: (a) disturbance caused by cameras; (b) variation in animalâdetection parameters across camera models; and (c) biased detection across individuals and age, sex, and behavioral classes. We propose several recommendations aimed at mitigating responses to CTs by wildlife. Our recommendations offer a platform for the development of more rigorous and robust behavioral studies using CT technology and, if adopted, would result in greater applied benefits for conservation and management
Difference in fit parameter values between the Young and Old CD8<sup>+</sup> T Cell Models.
<p>Difference in fit parameter values between the Young and Old CD8<sup>+</sup> T Cell Models.</p
Age related Ca<sup>2+</sup> changes in CD8<sup>+</sup> T cells.
<p>a) Cytoplasmic Ca<sup>2+</sup> levels in resting T cells. Mean and SEM from 4 different donors. AU = arbitrary units b) Representative trace of Ca<sup>2+</sup> dynamics following TCR stimulation with the related parameters studied, peak time, peak amplitude, baseline and decay. The integral corresponds to the colored area under the curve. c) Time to peak in seconds. d) Fast decay time constant in minutes. For c-d), the data represents the mean of each calculated parameters for each donor and its standard deviation. The red diamonds correspond to the parameter calculated if the Ca<sup>2+</sup> time courses are averaged for all donors for a specific day in culture.</p
An oxidative shift in redox potential with ex vivo T cell expansion.
<p>Total glutathione levels (a) and corresponding GSH/GSSG redox potential (b) in CD8<sup>+</sup> T cells with time in culture (n = 3). Statistical analysis: one-way ANOVA (p = 0.04) followed by Scheffeâs post-hoc test * p<0.05 between day 8 and day 16. Trx1 levels in CD8<sup>+</sup> T cells with time in culture. c) Total, reduced and oxidized Trx1 levels for a representative donor. DTT-treated lysate is included as a reduced control and diamide-treated lysate is included as an oxidized control. d) Trx1 redox potential (n = 4). Statistical analysis: one-way Anova (p = 0.007) followed by Scheffeâs post-hoc test * p<0.05 between day 4 and days 16â24. ** p<0.05 between days 8â12 and days 20â24.</p