Justice Arts: Making the Arts Accessible to People in the Juvenile and Adult Criminal Justice System - A Feasibility Study for the Creation of a National Network Summary Report June 2016

In June 2015, more than 220 people from 22 states gathered at the University of San Francisco to participate in a four day conference to share stories, best practices and work they were doing in adult and juvenile prisons and correctional facilities throughout the United States and in England. This conference, "Arts in Corrections: Opportunities for Justice and Rehabilitation," was presented by California Lawyers for the Arts and the William James Association with the support of the National Endowment for the Arts, the California Arts Council and the California Department of Corrections and Rehabilitation, as well as the University of San Francisco and several private foundations.During the conference, a group of approximately 40 persons met in two facilitated sessions to discuss the possibility of creating a national network. A smaller group volunteered to participate in an informal steering committee to investigate the needs and benefits of such an organization. In the fall of 2015 the steering committee designed an electronic survey to receive feedback about this concept from a larger number of practitioners around the country. They received 205 responses, with 94% saying that they would support or join such an organization--a strong mandate to explore next steps to create a national network that will help artists and programs

ASSOCIATIONS OF TOBACCO RETAILER DENSITY WITH NEIGHBORHOOD SOCIODEMOGRAPHICS, INDIVIDUAL SMOKING BEHAVIORS, & COPD HOSPITAL DISCHARGE RATES: A SPATIAL HEALTH APPROACH

Background. Tobacco retailer density (TRD) is a measure of the availability of tobacco retailers in an area. Although some studies indicate that TRD is not equitably distributed across neighborhoods, they are limited by inconsistent TRD measures and do not account for the sociodemographics of surrounding areas. Even fewer studies consider the impact of TRD on smoking behaviors or associated health outcomes at the national level. This dissertation encompasses four 2014 cross-sectional studies to investigate these gaps. Methods. Study 1 investigated associations of TRD with census tract-level sociodemographic characteristics in the contiguous U.S., comparing associations across four commonly used density measures. Study 2 used spatial econometric modeling to determine whether the sociodemographics of neighboring census tracts additionally impact a focal tract’s TRD. Study 3 used multilevel modeling to investigate whether county-level TRD is associated with an individual’s likelihood of smoking and making a quit attempt in a national sample. Finally, Study 4 examined associations between county-level TRD and chronic obstructive pulmonary disease (COPD) related hospital discharge outcomes in 1510 counties. Results. In Study 1, tracts with a greater proportion of residents living below 150% of the federal poverty level (FPL) had higher TRD. Disparities between TRD and percent non-Hispanic Black, Hispanic or Latino, and vacant housing units, however, were sensitive to the TRD measure operationalized. In Study 2, a tract that was surrounded by neighboring tracts with a higher proportion of individuals living below 150% FPL, non-Hispanic Black residents, and Hispanic or Latino residents, was associated with greater TRD. In Studies 3 and 4, higher county-level TRD was associated with a greater likelihood of every-day smoking and higher county-level COPD-related discharges, hospital stays, and financial costs. Conclusion. In 2014, there were racial, ethnic, and socioeconomic disparities in TRD, and both the neighboring attributes of census tracts and the TRD measures used may impact observed disparities. County-level TRD is also associated with daily smoking and greater hospital discharges rates and costs: longitudinal studies are needed to better disentangle the mechanisms driving these associations. Integrated tobacco control policies that include retailer reduction strategies may help ameliorate smoking behaviors and related disease burdens.Doctor of Public Healt

Comorbidities and Medication Adherence among Older Individuals Living with HIV in the United States

The number of people living with HIV (PLWH) ≥65 years old is increasing in the United States (US) as PLWH live longer. In 2015, there were nearly 1 million people living with diagnosed HIV in the US and under 10% were age ≥65. By 2035, the proportion of PLWH in this age group is projected to be 27%. Like the general population of elderly individuals, as they age, PLWH face age-related comorbidities, many of which require routine medical care and daily medications, in addition to daily antiretroviral therapy (ART) for treatment of HIV. Previous research has found that PLWH develop these conditions at higher rates and earlier ages than HIV-negative individuals. Therefore, elderly PLWH are particularly vulnerable to the challenges associated with multimorbidity and polypharmacy, including remaining adherent to their medications. However, in the context of PLWH, “older” has typically been defined as \u3e50 years old, with few studies analyzing PLWH age ≥65, a relevant population given Medicare insurance eligibility in the US. Additionally, there is a dearth of literature focusing on older HIV-positive women and comorbidities. Gaining a better understanding of the non-HIV-related comorbid disease and non-ART comedication burden among PLWH age ≥65 is important because these comorbidities often require care coordination among multiple providers and because comorbidities may negatively impact adherence to ART. With a focus on PLWH aged ≥65 living in the US, the objectives of this dissertation were: (1) to compare the non-HIV disease and non-ART medication burden among PLWH and HIV-negative individuals; (2) to describe patterns of non-HIV condition co-occurrence among PLWH and HIV-negative individuals; and (3) to examine the impact of comorbid disease and comedication burden on ART adherence among PLWH. Using data from 2010 to 2015 in the IBM Watson Health MarketScan® Medicare Supplemental insurance database, I selected PLWH and HIV-negative individuals ≥65 years old based on diagnoses on medical claims and pharmacy claims for ART. Outcomes included common diagnoses and medication classes, prevalence and number of non-HIV conditions, daily non-ART medications, and ART medication adherence (using proportion of days covered (PDC) over a 1-year period, all based on medical and pharmacy claims. To address the first dissertation objective, I examined age-standardized prevalence rates for non-HIV conditions and prevalence ratios (PRs) and fit sex-stratified multivariable generalized linear models for the number of non-HIV conditions and number of daily non-ART medications. For the second dissertation objective, I used latent class analysis to identify classes of individuals based on the presence of non-HIV comorbid conditions. Separate latent class models were fit to cohorts of PLWH, HIV-negative individuals, and HIV-negative individuals matched to the PLWH cohort on demographic characteristics. For the third dissertation objective, I modeled the odds of being adherent to ART (defined as PDC ≥80%) using separate adjusted logistic regression models for PLWH treated with ART with the number of comorbid conditions, the number of comedications, and comorbidity classes as the exposures of interest. Dissertation Objective 1: I assessed non-HIV conditions and daily non-ART medications among 2,359 elderly PLWH and 2,010,513 elderly HIV-negative individuals. PLWH were younger (mean age 71 vs. 76 years) and a larger proportion were men (81% vs. 45%). The most common diagnoses among both HIV-positive and HIV-negative cohorts were hypertension and dyslipidemia. Most non-HIV conditions were more prevalent among PLWH. The largest absolute difference was in anemia (29.6 cases per 100 people vs.11.7) and the largest relative difference was in hepatitis C (PR=22.0). The unadjusted mean number of non-HIV conditions and daily non-ART medications were higher for PLWH (4.61 conditions and 3.79 medications) than HIV-negative individuals (3.94 conditions and 3.41 medications), respectively. In generalized linear models with log link and negative binomial distribution where the outcome was the number of non-HIV conditions, PLWH had significantly more non-HIV conditions than HIV-negative individuals (ratios: men=1.272, [95% CI 1.233-1.312]; women=1.326 [1.245-1.413]). Among those with \u3e0 daily non-ART medications, men with HIV had significantly more non-ART medications than HIV-negative men (ratio=1.178 [1.133-1.226]) in a generalized linear model with log link and gamma distribution where the outcome was number of non-ART medications. Dissertation Objective 2: When conditions with prevalence ≥15% among PLWH were included in latent class models, a 3-class solution was identified for cohorts of PLWH, all HIV-negative individuals, and matched HIV-negative individuals: a sickest class with high probabilities of multiple non-HIV conditions, a class characterized by hypertension and dyslipidemia, and a healthiest class with low probabilities of non-HIV conditions. Nearly 20% of the PLWH were assigned to the sickest class compared to 10.5% of the matched HIV-negative cohort, with PLWH having higher probabilities of specific non-HIV diagnoses, including kidney disease and anemia. Dissertation Objective 3: Lastly, when analyzing the odds of being adherent to ART among 1,644 elderly PLWH with logistic regression models, I found that odds of non-adherence were significantly higher among PLWH with 5-6 comorbidities compared to PLWH with 0-2 comorbidities (adjusted odds ratio [AOR]=1.420 [95% CI 1.035-1.947]). After controlling for the number of comedications, PLWH with 5-6 comorbid conditions (AOR=1.589 [95% CI 1.131-2.232]) and PLWH with ≥7 conditions (AOR=1.528 [95% CI 1.049-2.225]) were 50%-60% more likely to be non-adherent than PLWH with 0-2 conditions. Additionally, PLWH belonging to the hypertension/dyslipidemia/diabetes comorbidity class were more likely to be non-adherent than PLWH in the healthiest class (AOR=1.319 [95% CI 1.047-1.661]). In conclusion, I found that the disease burden associated with aging is substantially higher among PLWH age ≥65 than similarly aged HIV-negative individuals, and that there was a trend of decreasing ART adherence with increasing comorbid disease burden among PLWH. Due to the greater comorbid disease burden, elderly PLWH in the US require additional services and care coordination to effectively manage both HIV and comorbid conditions, particularly those who have a large number of comorbid conditions. Because multimorbidity may have a negative impact of ART adherence, there is a need for interventions focused on primary and secondary prevention of comorbidities and ART adherence among elderly PLWH. Future analyses may include additional analyses with larger samples of older HIV-positive women, assessments of comorbidities and ART medication adherence using other data sources where HIV-specific variables like duration of infection, CD4 and viral load are available, an evaluation of PLWH’s adherence to comedications, such as antidiabetes medications and antihypertensives, and an estimation of the cost impact of comorbid conditions among older PLWH in the US

Racial and Ethnic Differences in What Smokers Report Paying for Their Cigarettes

Smoking rates and tobacco-related health problems vary by race and ethnicity. We explore whether cigarette prices, a determinant of tobacco use, differ across racial and ethnic groups, and whether consumer behaviors influence these differences

A systems approach to designing next generation vaccines: Combining α-galactose modified antigens with nanoparticle platforms

Innovative vaccine platforms are needed to develop effective countermeasures against emerging and re-emerging diseases. These platforms should direct antigen internalization by antigen presenting cells and promote immunogenic responses. This work describes an innovative systems approach combining two novel platforms, αGalactose (αGal)-modification of antigens and amphiphilic polyanhydride nanoparticles as vaccine delivery vehicles, to rationally design vaccine formulations. Regimens comprising soluble αGal-modified antigen and nanoparticle-encapsulated unmodified antigen induced a high titer, high avidity antibody response with broader epitope recognition of antigenic peptides than other regimen. Proliferation of antigen-specific CD4 + T cells was also enhanced compared to a traditional adjuvant. Combining the technology platforms and augmenting immune response studies with peptide arrays and informatics analysis provides a new paradigm for rational, systems-based design of next generation vaccine platforms against emerging and re-emerging pathogens

Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer

Background: Pre-clinical studies suggest AZD1775, a WEE1 kinase inhibitor, potentiates the activity of various chemotherapeutic agents. Methods: WISTERIA was a prospective, parallel two-group, open-label, dose-finding, phase I clinical trial. Eligible patients had histologically confirmed oral, laryngeal, or hypopharyngeal squamous cell carcinoma, ECOG performance status 0/1, and aged ≥18-to-≤70 years. Primary outcomes were adverse events and defining recommended dose and schedule of AZD1775 in combination with cisplatin in pre-operative (Group A), or with cisplatin/radiotherapy in post-operative (Group B) patients. Dose determination was guided by a modified time-to-event continual reassessment method (mTITE-CRM). Results: Between 30-Oct-2017 and 15-Jul-2019, nine patients were registered: Three into Group A and six into Group B. WISTERIA was closed early due to poor recruitment. Five dose-limiting toxicities (DLTs) were reported in four Group B patients. Seven serious adverse events were reported in four patients: One in Group A, and three in Group B. Three were related to treatment. No treatment-related deaths were reported. Conclusions: WISTERIA did not complete its primary objectives due to poor recruitment and toxicities reported in Group B. However, use of the novel mTITE-CRM improved flexibility in reducing accrual suspension periods and should be considered for future trials in complex patient populations. Clinical Trial Registration: ISRCTN7629195

S1 is associated with chronic low back pain: a functional and structural MRI study

A fundamental characteristic of neural circuits is the capacity for plasticity in response to experience. Neural plasticity is associated with the development of chronic pain disorders. In this study, we investigated 1) brain resting state functional connectivity (FC) differences between patients with chronic low back pain (cLBP) and matched healthy controls (HC); 2) FC differences within the cLBP patients as they experienced different levels of endogenous low back pain evoked by exercise maneuvers, and 3) morphometric differences between cLBP patients and matched HC. We found the dynamic character of FC in the primary somatosensory cortex (S1) in cLBP patients, i.e., S1 FC decreased when the patients experienced low intensity LBP as compared with matched healthy controls, and FC at S1 increased when cLBP patients experienced high intensity LBP as compared with the low intensity condition. In addition, we also found increased cortical thickness in the bilateral S1 somatotopically associated with the lower back in cLBP patients as compared to healthy controls. Our results provide evidence of structural plasticity co-localized with areas exhibiting FC changes in S1 in cLBP patients

The role of Glial cell derived neurotrophic factor in head and neck cancer

Glial cell-derived neurotrophic factor (GDNF) is reported to promote the survival of neurons and salivary gland regeneration after radiation damage. This study investigated the effect of GDNF on cell migration, growth, and response to radiation in preclinical models of head and neck squamous cell carcinoma (HNSCC) and correlated GDNF expression to treatment outcomes in HNSCC patients. Our ultimate goal is to determine whether systemic administration of GDNF at high dose is safe for the management of hyposalivation or xerostomia in HNSCC patients. Three HPV-positive and three HPV-negative cell lines were examined for cell migration, growth, and clonogenic survival in vitro and tumor growth assay in vivo. Immunohistochemical staining of GDNF, its receptors GFRα1 and its co-receptor RET was performed on two independent HNSCC tissue microarrays (TMA) and correlated to treatment outcomes. Results showed that GDNF only enhanced cell migration in two HPV-positive cells at supra-physiologic doses, but not in HPV-negative cells. GDNF did not increase cell survival in the tested cell lines post-irradiation. Likewise, GDNF treatment affected neither tumor growth in vitro nor response to radiation in xenografts in two HPV-positive and two HPV-negative HNSCC models. High stromal expression of GDNF protein was associated with worse overall survival in HPV-negative HNSCC on multivariate analysis in a combined cohort of patients from Stanford University (n = 82) and Washington University (n = 189); however, the association between GDNF gene expression and worse survival was not confirmed in a separate group of HPV-negative HNSCC patients identified from the Cancer Genome Atlas (TCGA) database. Based on these data, we do not believe that GNDF is a safe systemic treatment to prevent or treat xerostomia in HNSCC and a local delivery approach such as intraglandular injection needs to be explored

Are All Placebo Effects Equal? Placebo Pills, Sham Acupuncture, Cue Conditioning and Their Association

Placebo treatments and healing rituals have been used to treat pain throughout history. The present within-subject crossover study examines the variability in individual responses to placebo treatment with verbal suggestion and visual cue conditioning by investigating whether responses to different types of placebo treatment, as well as conditioning responses, correlate with one another. Secondarily, this study also examines whether responses to sham acupuncture correlate with responses to genuine acupuncture. Healthy subjects were recruited to participate in two sequential experiments. Experiment one is a five-session crossover study. In each session, subjects received one of four treatments: placebo pills (described as Tylenol), sham acupuncture, genuine acupuncture, or no treatment rest control condition. Before and after each treatment, paired with a verbal suggestion of positive effect, each subject's pain threshold, pain tolerance, and pain ratings to calibrated heat pain were measured. At least 14 days after completing experiment one, all subjects were invited to participate in experiment two, during which their analgesic responses to conditioned visual cues were tested. Forty-eight healthy subjects completed experiment one, and 45 completed experiment two. The results showed significantly different effects of genuine acupuncture, placebo pill and rest control on pain threshold. There was no significant association between placebo pills, sham acupuncture and cue conditioning effects, indicating that individuals may respond to unique healing rituals in different ways. This outcome suggests that placebo response may be a complex behavioral phenomenon that has properties that comprise a state, rather than a trait characteristic. This could explain the difficulty of detecting a signature for “placebo responders.” However, a significant association was found between the genuine and sham acupuncture treatments, implying that the non-specific effects of acupuncture may contribute to the analgesic effect observed in genuine acupuncture analgesia.National Center for Complementary and Alternative Medicine (U.S.) (R01AT005280

Rational Design of Pathogen-Mimicking Amphiphilic Materials as Nanoadjuvants

An opportunity exists today for cross-cutting research utilizing advances in materials science, immunology, microbial pathogenesis, and computational analysis to effectively design the next generation of adjuvants and vaccines. This study integrates these advances into a bottom-up approach for the molecular design of nanoadjuvants capable of mimicking the immune response induced by a natural infection but without the toxic side effects. Biodegradable amphiphilic polyanhydrides possess the unique ability to mimic pathogens and pathogen associated molecular patterns with respect to persisting within and activating immune cells, respectively. The molecular properties responsible for the pathogen-mimicking abilities of these materials have been identified. The value of using polyanhydride nanovaccines was demonstrated by the induction of long-lived protection against a lethal challenge of Yersinia pestis following a single administration ten months earlier. This approach has the tantalizing potential to catalyze the development of next generation vaccines against diseases caused by emerging and re-emerging pathogens