ALTERNATIVE METHODS FOR DISTRIBUTING STATE AID TO LOCAL GOVERNMENTS IN NEW YORK

This paper simulates alternative distributions of general purpose state aid to local governments under different combinations of criteria: tax capacity, effort, and revenue needs. Revenue needs are based on Tobit estimates of the costs of providing average levels of 16 categories of services. Segmenting the sample into high and low population jurisdictions provided a more realistic set of cost estimates. Available revenues or capacity are determined by multiplying each jurisdiction's tax bases by standard tax rates. A Need-Capacity gap, the difference between needed revenues and available revenues, is used as a needs-based distribution strategy for general purpose aid. Finally an effort gap, based on above average tax efforts was added to the Need-Capacity gap to define a Need-Capacity-Effort strategy.Public Economics,

Work-related correlates of occupational sitting in a diverse sample of employees in Midwest metropolitan cities

The worksite serves as an ideal setting to reduce sedentary time. Yet little research has focused on occupational sitting, and few have considered factors beyond the personal or socio-demographic level. The current study i) examined variation in occupational sitting across different occupations, ii) explored whether worksite level factors (e.g., employer size, worksite supports and policies) may be associated with occupational sitting. Between 2012 and 2013, participants residing in four Missouri metropolitan areas were interviewed via telephone and provided information on socio-demographic characteristics, schedule flexibility, occupation, work related factors, and worksite supports and policies. Occupational sitting was self-reported (daily minutes spent sitting at work), and dichotomized. Occupation-stratified analyses were conducted to identify correlates of occupational sitting using multiple logistic regressions. A total of 1668 participants provided completed data. Those employed in business and office/administrative support spent more daily occupational sitting time (median 330 min) compared to service and blue collar employees (median 30 min). Few worksite supports and policies were sitting specific, yet factors such as having a full-time job, larger employer size, schedule flexibility, and stair prompt signage were associated with occupational sitting. For example, larger employer size was associated with higher occupational sitting in health care, education/professional, and service occupations. Work-related factors, worksite supports and policies are associated with occupational sitting. The pattern of association varies among different occupation groups. This exploratory work adds to the body of research on worksite level correlates of occupational sitting. This may provide information on priority venues for targeting highly sedentary occupation groups

The Gender Wage Gap in the New Millennium: An Analysis of the United States 2000-2020

This study examines the earnings differential in each year from 2000-2020 to determine if the gender pay gap has changed in recent years. We estimate average weekly wages for full-time, year-round workers for men and women to determine women’s wages relative to men’s wages for each year. Our results show that although average earnings for women relative to men have increased since 2000 when adjusting for individual worker characteristics, we find little progress in shrinking the gender wage gap. This result is even more discouraging since women’s education rates have increased at a significantly higher rate during this time

Pharmacist-led management of chronic pain in primary care:results from a randomised controlled exploratory trial

To compare the effectiveness of pharmacist medication review, with or without pharmacist prescribing, with standard care, for patients with chronic pain

Physiologically-based Pharmacokinetic Modeling of Drugs with Transporter-mediated Disposition: Prediction of Vincristine and Amoxicillin Disposition in Children

The use of physiologically-based pharmacokinetic (PBPK) models to predict pediatric pharmacokinetics (PK) and select optimal doses is increasingly common. However, its application to pediatric drugs with transporter-mediated disposition has been limited by challenges in modeling drugs with a complicated interplay between metabolism and transport and a need for transporter ontogeny data. The goal of this dissertation was to develop bottom-up PBPK models to predict the PK of two drugs with transporter-mediated disposition in pediatric populations: (1) vincristine, an intravenously administered anti-cancer agent that is cleared hepatically by the drug metabolizing enzymes cytochrome P450 (CYP) 3A4/5 and the efflux transporter P-glycoprotein (P-gp), and (2) amoxicillin, an orally administered antibiotic that requires the intestinal apical (AP) uptake transporter peptide transporter 1 (PEPT1) for absorption. PBPK modeling of vincristine in adults that incorporated hepatic CYP3A4/5-mediated metabolism and P-gp-mediated efflux initially underestimated the extent of distribution of vincristine. Model predictions were improved by incorporating binding of vincristine to the microtubule protein β-tubulin. When the adult PBPK model was adapted to the pediatric population, simulating a 4.9-fold higher hypothetical expression level of β-tubulin in children as compared to adults improved predictions of the pediatric PBPK model. Despite its implied role in vincristine clearance, P-gp-mediated efflux was not a key parameter in the model, leading to the conclusion that vincristine uptake into hepatocytes is the rate-limiting step in its clearance, rather than its efflux. Amoxicillin demonstrates dose-dependent oral bioavailability despite its hydrophilicity and charge at physiological pH, properties that are consistent with a contribution of transporters and paracellular transport to its absorption. Studies performed in Caco-2 cell monolayers and adult human intestinal epithelia suggested that PEPT1 and an organic anion-transporting polypeptide (OATP) are involved in the AP uptake of amoxicillin. Efficient basolateral (BL) egress of amoxicillin implicates a BL transporter, likely the bidirectional peptide transporter. A relatively large (~20%) contribution of paracellular transport to the overall absorption of amoxicillin was observed. Lastly, PBPK models of oral amoxicillin predicted PK in adults, and in young children (≤ 5 years of age) after incorporating pediatric GI physiology and amoxicillin renal clearance.Doctor of Philosoph

BCL-W has a fundamental role in B cell survival and lymphomagenesis.

Compromised apoptotic signaling is a prerequisite for tumorigenesis. The design of effective therapies for cancer treatment depends on a comprehensive understanding of the mechanisms that govern cell survival. The antiapoptotic proteins of the BCL-2 family are key regulators of cell survival and are frequently overexpressed in malignancies, leading to increased cancer cell survival. Unlike BCL-2 and BCL-XL, the closest antiapoptotic relative BCL-W is required for spermatogenesis, but was considered dispensable for all other cell types. Here, however, we have exposed a critical role for BCL-W in B cell survival and lymphomagenesis. Loss of Bcl-w conferred sensitivity to growth factor deprivation-induced B cell apoptosis. Moreover, Bcl-w loss profoundly delayed MYC-mediated B cell lymphoma development due to increased MYC-induced B cell apoptosis. We also determined that MYC regulates BCL-W expression through its transcriptional regulation of specific miR. BCL-W expression was highly selected for in patient samples of Burkitt lymphoma (BL), with 88.5% expressing BCL-W. BCL-W knockdown in BL cell lines induced apoptosis, and its overexpression conferred resistance to BCL-2 family-targeting BH3 mimetics. Additionally, BCL-W was overexpressed in diffuse large B cell lymphoma and correlated with decreased patient survival. Collectively, our results reveal that BCL-W profoundly contributes to B cell lymphoma, and its expression could serve as a biomarker for diagnosis and aid in the development of better targeted therapies

Insulin clearance and the incidence of type 2 diabetes in Hispanics and African Americans: the IRAS Family Study.

ObjectiveWe aimed to identify factors that are independently associated with the metabolic clearance rate of insulin (MCRI) and to examine the association of MCRI with incident type 2 diabetes in nondiabetic Hispanics and African Americans.Research design and methodsWe investigated 1,116 participants in the Insulin Resistance Atherosclerosis Study (IRAS) Family Study with baseline examinations from 2000 to 2002 and follow-up examinations from 2005 to 2006. Insulin sensitivity (S(I)), acute insulin response (AIR), and MCRI were determined at baseline from frequently sampled intravenous glucose tolerance tests. MCRI was calculated as the ratio of the insulin dose over the incremental area under the curve of insulin. Incident diabetes was defined as fasting glucose ≥126 mg/dL or antidiabetic medication use by self-report.ResultsWe observed that S(I) and HDL cholesterol were independent positive correlates of MCRI, whereas fasting insulin, fasting glucose, subcutaneous adipose tissue, visceral adipose tissue, and AIR were independent negative correlates (all P < 0.05) at baseline. After 5 years of follow-up, 71 (6.4%) participants developed type 2 diabetes. Lower MCRI was associated with a higher risk of incident diabetes after adjusting for demographics, lifestyle factors, HDL cholesterol, indexes of obesity and adiposity, and insulin secretion (odds ratio 2.01 [95% CI 1.30-3.10], P = 0.0064, per one-SD decrease in loge-transformed MCRI).ConclusionsOur data showed that lower MCRI predicts the incidence of type 2 diabetes

Meningococcal Disease in Patients With Human Immunodeficiency Virus Infection: A Review of Cases Reported Through Active Surveillance in the United States, 2000-2008.

BackgroundAlthough human immunodeficiency virus (HIV) infection is an established risk factor for several bacterial infections, the association between HIV infection and meningococcal disease remains unclear.MethodsExpanded chart reviews were completed on persons with meningococcal disease and HIV infection reported from 2000 through 2008 from 9 US sites participating in an active population-based surveillance system for meningococcal disease. The incidence of meningococcal disease among patients meeting Centers for Disease Control and Prevention acquired immune deficiency syndrome (AIDS) surveillance criteria was estimated using data from the National HIV Surveillance System for the participating sites.ResultsThirty-three cases of meningococcal disease in individuals with HIV infection were reported from participating sites, representing 2.0% of all reported meningococcal disease cases. Most (75.8%) persons with HIV infection were adult males aged 25 to 64 years old. Among all meningococcal disease cases aged 25 to 64 years old, case fatality ratios were similar among HIV-infected and HIV-uninfected persons (13.3% vs 10.6%; P = .6). The cumulative, mean incidence of meningococcal disease among patients aged 25 to 64 years old with HIV infection ever classified as AIDS was 3.5 cases per 100000 person years (95% confidence interval [CI], 2.1-5.6), compared with 0.3 cases per 100000 person years (95% CI, 0.3-0.3) for persons of the same age group not reported to have AIDS (relative risk = 12.9; 95% CI, 7.9-20.9).ConclusionsIndividuals with HIV infection meeting the AIDS surveillance case definition have a higher incidence of meningococcal disease compared with the general adult population