A Dynamic Stochastic Model of Lifetime Smoking Behavior

This dissertation discusses results obtained through formulation and estimation of a dynamic stochastic model that captures individual smoking decision making, health expectations, and longevity over the life cycle. The standard rational addiction model is augmented with a Bayesian learning process about the health marker transition technology to evaluate the importance of personalized health information in the decision to smoke cigarettes. Additionally, the model is well positioned to assess how smoking and smoking cessation impact morbidity and mortality outcomes while taking into consideration the potential for dynamic selection of smoking behaviors. This research also provides a novel approach to the empirical construction of the theoretically common ""smoking stock"" that facilitates the estimation of investment and depreciation parameters. The structural parameters are estimated using rich longitudinal health and smoking data from the Framingham Heart Study: Offspring Cohort. Results suggest that there exists heterogeneity across individuals in the pathways by which smoking effects health. Furthermore, upon smoking, the estimated parameters suggest a positive reinforcement effect and a negative withdrawal effect, both of which encourage future smoking. I find that only in the case of very large change in an individual's health markers will the associated change in beliefs induce individuals to quit smoking. Generally, personalized health marker information is not found to influence smoking behavior relative to chronic health shocks themselves. The dissertation also presents evidence of health selection in smoking behavior that, when not modeled, may cause an overstatement of the direct effect of smoking on morbidity and mortality

Results at 24 months from the prospective, randomized, multicenter Investigational Device Exemption trial of ProDisc-C versus anterior cervical discectomy and fusion with 4-year follow-up and continued access patients.

BackgroundCervical total disk replacement (TDR) is intended to address pain and preserve motion between vertebral bodies in patients with symptomatic cervical disk disease. Two-year follow-up for the ProDisc-C (Synthes USA Products, LLC, West Chester, Pennsylvania) TDR clinical trial showed non-inferiority versus anterior cervical discectomy and fusion (ACDF), showing superiority in many clinical outcomes. We present the 4-year interim follow-up results.MethodsPatients were randomized (1:1) to ProDisc-C (PDC-R) or ACDF. Patients were assessed preoperatively, and postoperatively at 6 weeks and 3, 6, 12, 18, 24, 36, and 48 months. After the randomized portion, continued access (CA) patients also underwent ProDisc-C implantation, with follow-up visits up to 24 months. Evaluations included Neck Disability Index (NDI), Visual Analog Scale (VAS) for pain/satisfaction, and radiographic and physical/neurologic examinations.ResultsRandomized patients (103 PDC-R and 106 ACDF) and 136 CA patients were treated at 13 sites. VAS pain and NDI score improvements from baseline were significant for all patients (P < .0001) but did not differ among groups. VAS satisfaction was higher at all time points for PDC-R versus ACDF patients (P = .0499 at 48 months). The percentage of patients who responded yes to surgery again was 85.6% at 24 months and 88.9% at 48 months in the PDC-R group, 80.9% at 24 months and 81.0% at 48 months in the ACDF group, and 86.3% at 24 months in the CA group. Five PDC-R patients (48 months) and no CA patients (24 months) had index-level bridging bone. By 48 months, approximately 4-fold more ACDF patients required secondary surgery (3 of 103 PDC-R patients [2.9%] vs 12 of 106 ACDF patients [11.3%], P = .0292). Of these, 6 ACDF patients (5.6%) required procedures at adjacent levels. Three CA patients required secondary procedures (24 months).ConclusionsOur 4-year data support that ProDisc-C TDR and ACDF are viable surgical options for symptomatic cervical disk disease. Although ACDF patients may be at higher risk for additional surgical intervention, patients in both groups show good clinical results at longer-term follow-up

Population genetics of Cobia (Rachycentron canadum): implications for fishery management along the coast of the southeastern United States

Cobia (Rachycentron canadum) is a pelagic, migratory species with a transoceanic distribution in tropical and subtropical waters. Recreational fishing pressure on Cobia in the United States has increased substantially during the last decade, especially in areas of its annual inshore aggregations, making this species potentially susceptible to overfishing. Although Cobia along the Atlantic and Gulf coasts of the southeastern United States are currently managed as a single fishery, the genetic composition of Cobias in these areas is unclear. On the basis of a robust microsatellite data set from collections along the U.S. Atlantic coast (2008–09), offshore groups were genetically homogenous. However, the 2 sampled inshore aggregations (South Carolina and Virginia) were genetically distinct from each other, as well as from the offshore group. The recapture of stocked fish within their release estuary 2 years after release indicates that some degree of estuarine fidelity occurs within these inshore aggregations and supports the detection of their unique genetic structure at the population level. These results complement the observed high site fidelity of Cobias in South Carolina and support a recent study that confirms that Cobia spawn in the inshore aggregations. Our increased understanding of Cobia life history will be beneficial for determining the appropriate scale of fishery management for Cobia

Insurance-induced moral hazard: A dynamic model of within-year medical care decision making under uncertainty

Abstract Insurance-induced moral hazard may lead individuals to overconsume medical care. Many studies estimate this overconsumption using models that aggregate medical care decisions up to the annual level. Using employer-employee matched data from the Medical Expenditure Panel Survey (MEPS), I estimate the effect of moral hazard on medical care expenditure using a dynamic model of within-year medical care consumption that allows for endogenous health transitions, variation in medical care prices, and individual uncertainty within a health insurance year. I then calculate moral hazard effects under a second set of conditions that are consistent with the assumptions of most annual decision-making models. The within-year decision-making model produces a moral hazard effect that is 24% larger than the alternative model. I also provide evidence of heterogeneous moral hazard effects, particularly between insured and uninsured individuals, and discuss related policy implications. The paper concludes with a counterfactual policy simulation that implements the individual mandate provision of the 2010 Patient Protection and Affordable Care Act. I find that full implementation of the individual mandate decreases the percentage of uninsured individuals in the population being analyzed from 11.8% to 6.0% and increases average medical care expenditure 77% among the newly insured. JEL Classification: C61, D81, G22, I12, I1

"Feed from the Service": Corruption and Coercion in the State-University Relations in Central Eurasia

Education in Central Eurasia has become one of the industries, most affected by corruption. Corruption in academia, including bribery, extortions, embezzlement, nepotism, fraud, cheating, and plagiarism, is reflected in the region’s media and addressed in few scholarly works. This paper considers corruption in higher education as a product of interrelations between the government and academia. A substantial block of literature considers excessive corruption as an indicator of a weak state. In contrast to standard interpretations, this paper argues that in non-democratic societies corruption is used on a systematic basis as a mechanism of direct and indirect administrative control over higher education institutions. Informal approval of corrupt activities in exchange for loyalty and compliance with the regime may be used in the countries of Central Eurasia for the purposes of political indoctrination. This paper presents the concept of corruption and coercion in the state-university relations in Central Eurasia and outlines the model which incorporates this concept and the “feed from the service” approach. It presents implications of this model for the state-university relations and the national educational systems in Central Eurasia in general and offers some suggestions on curbing corruption

PARP1 ADP-ribosylates lysine residues of the core histone tails

The chromatin-associated enzyme PARP1 has previously been suggested to ADP-ribosylate histones, but the specific ADP-ribose acceptor sites have remained enigmatic. Here, we show that PARP1 covalently ADP-ribosylates the amino-terminal histone tails of all core histones. Using biochemical tools and novel electron transfer dissociation mass spectrometric protocols, we identify for the first time K13 of H2A, K30 of H2B, K27 and K37 of H3, as well as K16 of H4 as ADP-ribose acceptor sites. Multiple explicit water molecular dynamics simulations of the H4 tail peptide into the catalytic cleft of PARP1 indicate that two stable intermolecular salt bridges hold the peptide in an orientation that allows K16 ADP-ribosylation. Consistent with a functional cross-talk between ADP-ribosylation and other histone tail modifications, acetylation of H4K16 inhibits ADP-ribosylation by PARP1. Taken together, our computational and experimental results provide strong evidence that PARP1 modifies important regulatory lysines of the core histone tails

A Double-Blind Randomized Phase I Clinical Trial Targeting ALVAC-HIV Vaccine to Human Dendritic Cells

BACKGROUND: We conducted a novel pilot study comparing different delivery routes of ALVAC-HIV (vCP205), a canarypox vaccine containing HIV gene inserts: env, gag and pol. We explored the concept that direct ex vivo targeting of human dendritic cells (DC) would enhance the immune response compared to either conventional intramuscular or intradermal injections of the vaccine alone. METHODOLOGY/PRINCIPAL FINDINGS: Healthy HIV-1 uninfected volunteers were administered ALVAC-HIV or placebo by intramuscular injection (i.m.), intradermal injection (i.d.) or subcutaneous injection (s.q.) of autologous ex vivo transfected DC at months 0, 1, 3 and 6. All vaccine delivery routes were well tolerated. Binding antibodies were observed to both the ALVAC vector and HIV-1 gp160 proteins. Modest cellular responses were observed in 2/7 individuals in the DC arm and 1/8 in the i.m. arm as determined by IFN-γ ELISPOT. Proliferative responses were most frequent in the DC arm where 4/7 individuals had measurable responses to multiple HIV-1 antigens. Loading DC after maturation resulted in lower gene expression, but overall better responses to both HIV-1 and control antigens, and were associated with better IL-2, TNF-α and IFN-γ production. CONCLUSIONS/SIGNIFICANCE: ALVAC-HIV delivered i.m., i.d. or s.q. with autologous ex vivo transfected DC proved to be safe. The DC arm was most immunogenic. Proliferative immune responses were readily detected with only modest cytotoxic CD8 T cell responses. Loading mature DC with the live viral vaccine induced stronger immune responses than loading immature DC, despite increased transgene expression with the latter approach. Volunteers who received the autologous vaccine loaded mature DC developed a broader and durable immune response compared to those vaccinated by conventional routes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00013572

Asymmetric Switching in a Homodimeric ABC Transporter: A Simulation Study

ABC transporters are a large family of membrane proteins involved in a variety of cellular processes, including multidrug and tumor resistance and ion channel regulation. Advances in the structural and functional understanding of ABC transporters have revealed that hydrolysis at the two canonical nucleotide-binding sites (NBSs) is co-operative and non-simultaneous. A conserved core architecture of bacterial and eukaryotic ABC exporters has been established, as exemplified by the crystal structure of the homodimeric multidrug exporter Sav1866. Currently, it is unclear how sequential ATP hydrolysis arises in a symmetric homodimeric transporter, since it implies at least transient asymmetry at the NBSs. We show by molecular dynamics simulation that the initially symmetric structure of Sav1866 readily undergoes asymmetric transitions at its NBSs in a pre-hydrolytic nucleotide configuration. MgATP-binding residues and a network of charged residues at the dimer interface are shown to form a sequence of putative molecular switches that allow ATP hydrolysis only at one NBS. We extend our findings to eukaryotic ABC exporters which often consist of two non-identical half-transporters, frequently with degeneracy substitutions at one of their two NBSs. Interestingly, many residues involved in asymmetric conformational switching in Sav1866 are substituted in degenerate eukaryotic NBS. This finding strengthens recent suggestions that the interplay of a consensus and a degenerate NBS in eukaroytic ABC proteins pre-determines the sequence of hydrolysis at the two NBSs