Resource Utilization and Cost-Effectiveness of Counselor- vs. Provider-Based Rapid Point-of-Care HIV Screening in the Emergency Department

Routine HIV screening in emergency department (ED) settings may require dedicated personnel. We evaluated the outcomes, costs and cost-effectiveness of HIV screening when offered by either a member of the ED staff or by an HIV counselor.We employed a mathematical model to extend data obtained from a randomized clinical trial of provider- vs. counselor-based HIV screening in the ED. We compared the downstream survival, costs, and cost-effectiveness of three HIV screening modalities: 1) no screening program; 2) an ED provider-based program; and 3) an HIV counselor-based program. Trial arm-specific data were used for test offer and acceptance rates (provider offer 36%, acceptance 75%; counselor offer 80%, acceptance 71%). Undiagnosed HIV prevalence (0.4%) and linkage to care rates (80%) were assumed to be equal between the screening modalities. Personnel costs were derived from trial-based resource utilization data. We examined the generalizability of results by conducting sensitivity analyses on offer and acceptance rates, undetected HIV prevalence, and costs.Estimated HIV screening costs in the provider and counselor arms averaged $8.10 and$31.00 per result received. The Provider strategy (compared to no screening) had an incremental cost-effectiveness ratio of $58,700/quality-adjusted life year (QALY) and the Counselor strategy (compared to the Provider strategy) had an incremental cost-effectiveness ratio of$64,500/QALY. Results were sensitive to the relative offer and acceptance rates by strategy and the capacity of providers to target-screen, but were robust to changes in undiagnosed HIV prevalence and programmatic costs.The cost-effectiveness of provider-based HIV screening in an emergency department setting compares favorably to other US screening programs. Despite its additional cost, counselor-based screening delivers just as much return on investment as provider based-screening. Investment in dedicated HIV screening personnel is justified in situations where ED staff resources may be insufficient to provide comprehensive, sustainable screening services

A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients

INTRODUCTION: The Oncotype DX assay was recently reported to predict risk for distant recurrence among a clinical trial population of tamoxifen-treated patients with lymph node-negative, estrogen receptor (ER)-positive breast cancer. To confirm and extend these findings, we evaluated the performance of this 21-gene assay among node-negative patients from a community hospital setting. METHODS: A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 and not treated with adjuvant chemotherapy. Cases (n = 220) were patients who died from breast cancer. Controls (n = 570) were breast cancer patients who were individually matched to cases with respect to age, race, adjuvant tamoxifen, medical facility and diagnosis year, and were alive at the date of death of their matched case. Using an RT-PCR assay, archived tumor tissues were analyzed for expression levels of 16 cancer-related and five reference genes, and a summary risk score (the Recurrence Score) was calculated for each patient. Conditional logistic regression methods were used to estimate the association between risk of breast cancer death and Recurrence Score. RESULTS: After adjusting for tumor size and grade, the Recurrence Score was associated with risk of breast cancer death in ER-positive, tamoxifen-treated and -untreated patients (P = 0.003 and P = 0.03, respectively). At 10 years, the risks for breast cancer death in ER-positive, tamoxifen-treated patients were 2.8% (95% confidence interval [CI] 1.7–3.9%), 10.7% (95% CI 6.3–14.9%), and 15.5% (95% CI 7.6–22.8%) for those in the low, intermediate and high risk Recurrence Score groups, respectively. They were 6.2% (95% CI 4.5–7.9%), 17.8% (95% CI 11.8–23.3%), and 19.9% (95% CI 14.2–25.2%) for ER-positive patients not treated with tamoxifen. In both the tamoxifen-treated and -untreated groups, approximately 50% of patients had low risk Recurrence Score values. CONCLUSION: In this large, population-based study of lymph node-negative patients not treated with chemotherapy, the Recurrence Score was strongly associated with risk of breast cancer death among ER-positive, tamoxifen-treated and -untreated patients

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Applying Behavioral and Physiological Measures to Assess the Relative Impact of the Prolonged COVID-19 Pandemic Closure on Two Mammal Species at the Oregon Zoo: Cheetah (A. jubatus) and Giraffe (G. c. reticulata and G. c. tippelskirchii)

The effect of visitor presence on zoo animals has been explored in numerous studies over the past two decades. However, the opportunities for observations without visitors have been very limited at most institutions. In 2020, the Oregon Zoo was closed, in response to the global SARS-CoV-2 (COVID-19) pandemic, from 15 March 2020 to 12 July 2020, resulting in approximately four consecutive months without visitor presence. This study aimed to quantify potential behavioral and hormonal changes expressed during two transition periods in zoo visitor attendance: the initial time period before and after closure in March 2020 and time before and after reopening in July 2020. Fecal glucocorticoid metabolite (fGM) concentrations of resident giraffes (n = 2) and cheetahs (n = 2) were tracked using enzyme immunoassay (EIA) analyses. Average fGM concentrations during the two transition periods were compared using a two-way mixed ANOVA. Additionally, twice-weekly scan sampling was used to quantify behavioral observations across the transitions, which were analyzed as individual behavior proportions. Individual behavior proportions were compared across the Zoo’s opening status and time of day using Kruskal–Wallis (H) tests. The results of our analyses showed the following outcomes: (1) significant increases in fGM concentrations for cheetahs and giraffes between the transition periods but not within them; (2) a significant increase in time spent ‘not visible’ in the cheetahs in the second transition period; and (3) increased vigilance behaviors in the giraffes immediately after the Zoo’s closure. However, the changes observed in fGM concentrations may be more strongly correlated with concomitant social changes (giraffes) and some medical events (cheetahs) rather than with the Zoo’s opening status. Nevertheless, this study was able to quantify differences in behavioral frequencies and fGM concentration in cheetahs and giraffes at the Oregon Zoo during the times of transition between visitor’s presence and absence. The results indicate that, while there was a possible, but relatively minor impact of the presence and absence of visitors on some behaviors, the differences observed in fGM concentration may have been more affected by some of the concomitant social changes and medical events that happened during the same period than by the presence or absence of visitors

Longitudinal Analysis of Variability in Fecal Glucocorticoid Metabolite Concentrations in Three Orangutans (<i>Pongo pygmaeus pygmaeus</i> and <i>Pongo pygmaeus abelii</i>) before, during, and after Transition from a Regular Habitat Environment to Temporary Housing in Indoor Holding Facilities

Considerable research has been conducted on the effects of inter-institutional transfers, but far less consideration has been given to intra-institutional transfers and extended housing in off-habitat holding. On 15 May 2018, The Oregon Zoo’s orangutans (n = 3) were moved from the Red Ape Reserve (RAR) to the Veterinary Medical Center (VMC) indoor holding areas and remained there until 22 December 2020, resulting in over two years of housing in a facility not specifically designed for orangutans. This study aimed to quantify potential changes in fecal glucocorticoid metabolites (fGM) typically associated with increased adrenal activity as a result of transfers, as well as potential differences in fGM concentrations associated with housing in the two different types of locations. We collected fecal samples from all orangutans during three time periods: the initial housing at RAR (RAR1), the time spent at VMC holding (VMC), and the return to RAR (RAR2). Samples were analyzed using enzyme-immunoassay (EIA) analyses and compared using two-way ANOVA tests with Games–Howell post-hoc evaluations. The results of our analyses showed the following: (1) significant differences in fGM concentrations based on location in two orangutans, with the highest fGM concentration occurring in fecal samples collected at the VMC; and (2) a lack of significant fGM peaks following multiple intra-institutional transfers for all three orangutans. Though requiring further corroboration through future studies, we speculated that pre-transfer behavior training and intensive, continued care by familiar animal care staff may have helped to mitigate the stress responses commonly associated with transfers and major changes in housing. Furthermore, this study highlights the individualistic nature of the stress response, as illustrated by the substantial variation in fGM concentrations across different housing regimens in the three orangutans

Robust Sequence Determinants of α-Synuclein Toxicity in Yeast Implicate Membrane Binding.

Protein conformations are shaped by cellular environments, but how environmental changes alter the conformational landscapes of specific proteins in vivo remains largely uncharacterized, in part due to the challenge of probing protein structures in living cells. Here, we use deep mutational scanning to investigate how a toxic conformation of α-synuclein, a dynamic protein linked to Parkinson's disease, responds to perturbations of cellular proteostasis. In the context of a course for graduate students in the UCSF Integrative Program in Quantitative Biology, we screened a comprehensive library of α-synuclein missense mutants in yeast cells treated with a variety of small molecules that perturb cellular processes linked to α-synuclein biology and pathobiology. We found that the conformation of α-synuclein previously shown to drive yeast toxicity-an extended, membrane-bound helix-is largely unaffected by these chemical perturbations, underscoring the importance of this conformational state as a driver of cellular toxicity. On the other hand, the chemical perturbations have a significant effect on the ability of mutations to suppress α-synuclein toxicity. Moreover, we find that sequence determinants of α-synuclein toxicity are well described by a simple structural model of the membrane-bound helix. This model predicts that α-synuclein penetrates the membrane to constant depth across its length but that membrane affinity decreases toward the C terminus, which is consistent with orthogonal biophysical measurements. Finally, we discuss how parallelized chemical genetics experiments can provide a robust framework for inquiry-based graduate coursework