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Background: Opioid overdose deaths in the US rose dramatically in the past 16 years, creating an urgent national health crisis with no signs of immediate relief. In 2017, the President of the US officially declared the opioid epidemic to be a national emergency and called for additional resources to respond to the crisis. Distributing naloxone to community laypersons and people at high risk for opioid overdose can prevent overdose death, but optimal distribution methods have not yet been pinpointed.Methods: We conducted a sequential exploratory mixed methods design using qualitative data to inform an agent-based model to improve understanding of effective community-based naloxone distribution to laypersons to reverse opioid overdose. The individuals in the model were endowed with cognitive and behavioral variables and accessed naloxone via community sites such as pharmacies, hospitals, and urgent-care centers. We compared overdose deaths over a simulated 6-month period while varying the number of distribution sites (0, 1, and 10) and number of kits given to individuals per visit (1 versus 10). Specifically, we ran thirty simulations for each of thirteen distribution models and report average overdose deaths for each. The baseline comparator was no naloxone distribution. Our simulations explored the effects of distribution through syringe exchange sites with and without secondary distribution, which refers to distribution of naloxone kits by laypersons within their social networks and enables ten additional laypersons to administer naloxone to reverse opioid overdose.Results: Our baseline model with no naloxone distribution predicted there would be 167.9 deaths in a six month period. A single distribution site, even with 10 kits picked up per visit, decreased overdose deaths by only 8.3% relative to baseline. However, adding secondary distribution through social networks to a single site resulted in 42.5% fewer overdose deaths relative to baseline. That is slightly higher than the 39.9% decrease associated with a tenfold increase in the number of sites, all distributing ten kits but with no secondary distribution. This suggests that, as long as multiple kits are picked up per visit, adding secondary distribution is at least as effective as increasing sites from one to ten. Combining the addition of secondary distribution with an increase in sites from one to ten resulted in a 61.1% drop in deaths relative to the baseline. Adding distribution through a syringe exchange site resulted in a drop of approximately 65% of deaths relative to baseline. In fact, when enabling distribution through a clean-syringe site, the secondary distribution through networks contributed no additional drops in deaths.Conclusion: Community-based naloxone distribution to reverse opioid overdose may significantly reduce deaths. Optimal distribution methods may include secondary distribution so that the person who picks up naloxone kits can enable others in the community to administer naloxone, as well as targeting naloxone distribution to sites where individuals at high-risk for opioid overdose death are likely to visit, such as syringe-exchange programs. This study design, which paired exploratory qualitative data with agent-based modeling, can be used in other settings seeking to implement and improve naloxone distribution programs. [ABSTRACT FROM AUTHOR]

Developing BEPS models which predict energy usage to a high degree of accuracy can be extremely time consuming. As a result, assumptions are often made regarding the input data required. Making these assumptions without introducing a significant amount of uncertainty to the model can be difficult, and requires experience. Even so, rules of thumb from one geographic region are not automatically transferrable to other regions. This paper develops a methodology which can be used to determine useful guidelines for defining the most influential input data for an accurate BEPS model. Differential sensitivity analysis is carried out on parametric data gathered from five archetype dwelling models. The sensitivity analysis results are used in order to form a guideline minimum set of accurately defined input data. Although the guidelines formed apply specifically to Irish residential dwellings, the methodology and processes used in defining the guidelines is highly repeatable. The guideline minimum data set was applied to practical examples in order to be validated. Existing buildings were modelled, and only the parameters within the minimum data set are accurately defined. All building models predict annual energy usage to within 10% of actual measured data, with seasonal energy profiles well-matching. [ABSTRACT FROM AUTHOR]

Abstract: Young, African American and Latino gay, bisexual and other men who have sex with men (MSM) are disproportionately represented among new HIV cases according to the most recent national surveillance statistics. Analysts have noted that these racial/ethnic disparities in HIV among MSM exist within the wider context of sexual, mental and physical health disparities between MSM and heterosexuals. The intercorrelation of these adverse health outcomes among MSM, termed syndemics, has been theorized to be socially produced by a heterosexist social system that marginalizes lesbian, gay, bisexual, MSM and other sexual minorities. African American and Latino MSM experience overlapping systems of oppression that may increase their risk of experiencing syndemic health outcomes. In this paper, using data from twenty in-depth qualitative interviews with MSM living in four New York City (NYC) neighborhoods, we present accounts of neighborhood space, examining how space can both physically constitute and reinforce social systems of stratification and oppression, which in turn produce social disparities in sexual health outcomes. By analyzing accounts of emerging sexuality in neighborhood space, i.e. across time and space, we identify pathways to risk and contribute to our understanding of how neighborhood space is experienced by gay men, adding to our ability to support young men as they emerge in place and to shape the social topography of urban areas. [ABSTRACT FROM AUTHOR]

Abstract: Young, African American and Latino gay, bisexual and other men who have sex with men (MSM) are disproportionately represented among new HIV cases according to the most recent national surveillance statistics. Analysts have noted that these racial/ethnic disparities in HIV among MSM exist within the wider context of sexual, mental and physical health disparities between MSM and heterosexuals. The intercorrelation of these adverse health outcomes among MSM, termed syndemics, has been theorized to be socially produced by a heterosexist social system that marginalizes lesbian, gay, bisexual, MSM and other sexual minorities. African American and Latino MSM experience overlapping systems of oppression that may increase their risk of experiencing syndemic health outcomes. In this paper, using data from twenty in-depth qualitative interviews with MSM living in four New York City (NYC) neighborhoods, we present accounts of neighborhood space, examining how space can both physically constitute and reinforce social systems of stratification and oppression, which in turn produce social disparities in sexual health outcomes. By analyzing accounts of emerging sexuality in neighborhood space, i.e. across time and space, we identify pathways to risk and contribute to our understanding of how neighborhood space is experienced by gay men, adding to our ability to support young men as they emerge in place and to shape the social topography of urban areas. [Copyright &y& Elsevier]

Abstract: Buprenorphine is an effective long-term opioid agonist treatment. As the only pharmacological treatment for opioid dependence readily available in office-based settings, buprenorphine may facilitate a historic shift in addiction treatment from treatment facilities to general medical practices. Although many patients have benefited from the availability of buprenorphine in the United States, almost half of current prescribers are addiction specialists suggesting that buprenorphine treatment has not yet fully penetrated general practice settings. We examined factors affecting willingness to offer buprenorphine treatment among physicians with different levels of prescribing experience. Based on their prescribing practices, physicians were classified as experienced, novice, or as a nonprescriber and asked to assess the extent to which a list of factors impacted their prescription of buprenorphine. Several factors affected willingness to prescribe buprenorphine for all physicians: staff training; access to counseling and alternate treatment; visit time; buprenorphine availability; and pain medications concerns. Compared with other physicians, experienced prescribers were less concerned about induction logistics and access to expert consultation, clinical guidelines, and mental health services. They were more concerned with reimbursement. These data provide important insight into physician concerns about buprenorphine and have implications for practice, education, and policy change that may effectively support widespread adoption of buprenorphine. [Copyright &y& Elsevier]

The main aim of this study was to evaluate the therapeutic efficacy of an oil-in-water nanoemulsion formulation encapsulating DHA-SBT-1214, a novel omega-3 fatty acid conjugated taxoid prodrug, against prostate cancer stem cells. Nanoemulsions of DHA-SBT-1214 (NE-DHA-SBT-1214) were prepared and characterized. In vitro delivery efficiency and cytotoxicity of NE-DHA-SBT-1214 was compared with solution formulation in PPT2 cells. In vivo studies included analysis of comparative efficacy of NE-DHA-SBT-1214 with Abraxane ® and placebo nanoemulsions as well as post-treatment alternations in clonogenic and sphere-forming capabilities of the tumor cells. Qualitative intracellular uptake studies of dye encapsulated NEs by confocal imaging showed uptake by both monolayer and spheroid cultured PPT2 cells. Treatment of PPT2 cells with NE DHA-SBT-1214 (1nM-1μM for monolayer culture of cells grown on collagen-coated dishes for 48 h) induced complete cell death, showing higher efficacy as compared to the drug solution. This nanoemulsion (10nM-10μM) also showed toxicity in 3D culture of floating spheroids. Weekly intravenous administration of the NE-DHA-SBT-1214 to NOD/SCID mice bearing subcutaneous PPT2 tumor xenografts led to dramatic suppression of tumor growth compared to Abraxane ® and placebo nanoemulsion formulation. Viable cells that survived from this in vivo treatment regimen were no longer able to induce floating spheroids and holoclones, whereas control and Abraxane ® treated tumor cells induced a large number of both. The results show that NE-DHA-SBT-1214 possesses significant activity against prostate CD133 high /CD44+/ high tumor-initiating cells both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Multiple gestations resulting from IVF continue to be a major problem associated with maternal/neonatal morbidity and mortality including preterm labour/delivery, pre-eclampsia and post-partum haemorrhage. A prospective survey at a university IVF clinic evaluated the effect of education and insurance coverage on patients' preferences for single-embryo transfer (SET) versus double-embryo transfer (DET). Patients undergoing IVF treatment from September 2008 to October 2009 were included. The main outcome measure was patients' preference of SET versus DET. Patients were sent an educational handout describing maternal and fetal risks of twin gestation. A total of 163 patients (32.6% response rate) returned the pre- and post-education surveys regarding preferences for SET versus DET based on three different IVF insurance coverage scenarios (no coverage, two cycles covered and unlimited coverage). There were statistically significant differences in the preference for SET before and after education across all insurance scenarios (scenario 1, 42.0% versus 61.1%; scenario 2, 50.6% versus 71.0%; and scenario 3, 61.7% versus 79.6%; P < 0.001 for all scenarios). Before education, patients preferred SET more in the unlimited coverage scenario (61 .7%) versus no coverage (42.0%; p < 0.001). An educational handout and increasing the amount of insurance coverage significantly increased a patient's preference for SET. [ABSTRACT FROM AUTHOR]

Angiogenic defects in Id mutant mice inhibit the growth of tumor xenografts, providing a genetic model for antiangiogenic stress. Our work tests the consequences of such stress on progression of more physiological Pten+/− tumors. While tumor growth occurs despite impaired angiogenesis, disruption of vasculature by Id loss causes tumor cells to experience hypoxia and necrosis, the extent of which is tumor dependent. We show that bone-marrow-derived endothelial precursors contribute functionally to neovasculature of some but not all Pten+/− tumors, partially rescuing Id mutant phenotype. We demonstrate that loss of Id1 in tumor endothelial cells results in downregulation of several proangiogenic genes, including α6 and β4 integrins, matrix metalloprotease-2, and fibroblast growth factor receptor-1. Inhibition of these factors phenocopies loss of Id in in vivo angiogenesis assays. [Copyright &y& Elsevier]

Loneliness is associated with negative health outcomes, such as cardiovascular disease, cognitive impairment, dementia, physical functional decline, depression, and increased mortality risk, among HIV- positive and HIV-negative older men who have sex with men (MSM). Given these negative health outcomes, it is imperative to identify factors that minimize loneliness in these vulnerable groups. We sought to examine whether social-environmental resiliencies—defined as an individual's level of support, social bonding, and psychological sense of community among gay men—buffer against symptoms of loneliness. We analyzed longitudinal data from 1,255 older MSM with and without HIV infection, all of whom were enrolled in the Multicenter AIDS Cohort Study (MACS). Using longitudinal latent class analysis (LLCA), we identified three underlying classes (Social Connectors, Non-community Connectors, and Social Isolates) in the social environment of the sample. We assessed the prevalence of loneliness by these latent classes. By lagging social environmental factors over time, we were able to examine the temporal relationships between latent classes and subsequent loneliness. Consistent with our hypothesis, multivariate associations revealed that compared to Social Connectors with high levels of social support and social bonding and a strong perceived sense of community among gay men, Social Isolates (Prevalence Ratio (PR): 1.42; 95% CI: 1.08–1.88; p = 0.0120) and Non-community Connectors (PR: 1.34; 95% CI: 1.03–1.75; p = 0.0322) were more likely to experience loneliness after adjustment for covariates and baseline loneliness. There were no differences by HIV status. These longitudinal data allowed us to make causal inferences related to the social environmental resiliencies lowering the odds of loneliness among HIV-positive and HIV-negative older MSM. Developing individual- and community-level tailored interventions for these populations by leveraging social environmental resiliencies is key to reducing loneliness and promoting health. • Longitudinal latent class analysis identified three classes in the sample. • Three classes: Social Connectors, Non-community Connectors, and Social Isolates. • Social Isolates and Non-community Connectors more likely to experience loneliness. • Social environmental resiliencies reduce loneliness among HIV- and HIV+ older MSM. [ABSTRACT FROM AUTHOR]

The main aim of this study was to evaluate the therapeutic efficacy of an oil-in-water nanoemulsion formulation encapsulating DHA-SBT-1214, a novel omega-3 fatty acid conjugated taxoid prodrug, against prostate cancer stem cells. Nanoemulsions of DHA-SBT-1214 (NE-DHA-SBT-1214) were prepared and characterized. In vitro delivery efficiency and cytotoxicity of NE-DHA-SBT-1214 was compared with solution formulation in PPT2 cells. In vivo studies included analysis of comparative efficacy of NE-DHA-SBT-1214 with Abraxane® and placebo nanoemulsions as well as post-treatment alternations in clonogenic and sphere-forming capabilities of the tumor cells. Qualitative intracellular uptake studies of dye encapsulated NEs by confocal imaging showed uptake by both monolayer and spheroid cultured PPT2 cells. Treatment of PPT2 cells with NE DHA-SBT-1214 (1nM-1μM for monolayer culture of cells grown on collagen-coated dishes for 48 h) induced complete cell death, showing higher efficacy as compared to the drug solution. This nanoemulsion (10nM-10μM) also showed toxicity in 3D culture of floating spheroids. Weekly intravenous administration of the NE-DHA-SBT-1214 to NOD/SCID mice bearing subcutaneous PPT2 tumor xenografts led to dramatic suppression of tumor growth compared to Abraxane® and placebo nanoemulsion formulation. Viable cells that survived from this in vivo treatment regimen were no longer able to induce floating spheroids and holoclones, whereas control and Abraxane® treated tumor cells induced a large number of both. The results show that NE-DHA-SBT-1214 possesses significant activity against prostate CD133high/CD44+/high tumor-initiating cells both in vitro and in vivo. [ABSTRACT FROM AUTHOR]