Modeling long-term longitudinal HIV dynamics with application to an AIDS clinical study

A virologic marker, the number of HIV RNA copies or viral load, is currently used to evaluate antiretroviral (ARV) therapies in AIDS clinical trials. This marker can be used to assess the ARV potency of therapies, but is easily affected by drug exposures, drug resistance and other factors during the long-term treatment evaluation process. HIV dynamic studies have significantly contributed to the understanding of HIV pathogenesis and ARV treatment strategies. However, the models of these studies are used to quantify short-term HIV dynamics ($<$ 1 month), and are not applicable to describe long-term virological response to ARV treatment due to the difficulty of establishing a relationship of antiviral response with multiple treatment factors such as drug exposure and drug susceptibility during long-term treatment. Long-term therapy with ARV agents in HIV-infected patients often results in failure to suppress the viral load. Pharmacokinetics (PK), drug resistance and imperfect adherence to prescribed antiviral drugs are important factors explaining the resurgence of virus. To better understand the factors responsible for the virological failure, this paper develops the mechanism-based nonlinear differential equation models for characterizing long-term viral dynamics with ARV therapy. The models directly incorporate drug concentration, adherence and drug susceptibility into a function of treatment efficacy and, hence, fully integrate virologic, PK, drug adherence and resistance from an AIDS clinical trial into the analysis. A Bayesian nonlinear mixed-effects modeling approach in conjunction with the rescaled version of dynamic differential equations is investigated to estimate dynamic parameters and make inference. In addition, the correlations of baseline factors with estimated dynamic parameters are explored and some biologically meaningful correlation results are presented. Further, the estimated dynamic parameters in patients with virologic success were compared to those in patients with virologic failure and significantly important findings were summarized. These results suggest that viral dynamic parameters may play an important role in understanding HIV pathogenesis, designing new treatment strategies for long-term care of AIDS patients.Comment: Published in at http://dx.doi.org/10.1214/08-AOAS192 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Pure Exporter: Theory and Evidence

This paper provides the first evidence about pure exporters (i.e., firms exporting all of their output to the foreign market) -- a phenomenon overlooked and cannot be explained in the existing literature. It then offers a generalized model of Melitz (2003) for examining the existence and behavior of pure exporters. In particular, pure exporters arise when the export market is sufficiently large -- a situation more likely to hold in developing countries as opposed to large developed countries; and their productivity levels are above those of non-exporters, but below those of firms having both domestic sales and export. These theoretical predictions are borne out in a data of Chinese manufacturing firms for the period of 1998-2005.Pure Exporter, Firm Heterogeneity, Exporting Behavior

Contract Enforcement and Family Control of Business: Evidence from China

Family control of business is prevalent in developing economies, and one of the leading theories suggests that it is a response to weak contract enforcement in such economies. In this paper, we investigate the impacts of contract enforcement on the degree of family control of business using a sample of China's private enterprises. It is found that weaker contract enforcement is associated with the higher degree of family control of business. Our results are robust to the control for omitted variables and reserve causality issues, to the adjustment for the sample attrition bias, to the use of a sub-sample, and to the inclusion of other explanations for the family control of business.Family Control of Business, Contract Enforcement, China's Private Enterprises

Determinants of Entrepreneurial Activities in China

The institutional environment – including protection of private properties and contract enforcement – has been rather unfavorable for the emergence and development of China’s private enterprises. This is in sharp contrast to the case of the developed economies where the institutional environment is conductive to the entrepreneurial activities and only the personal attributes of would-be entrepreneurs determine their entrepreneurship decision. We thus propose a theoretical framework for the entrepreneurship decision in China with a focus on the role of institutional environment. Using a life-histories survey data of 2,854 respondents from twenty cities in China, we find strong support for the impacts of the institutional environment and its interactions with other determinants of entrepreneurship decision.

Anti-dark and Mexican-hat solitons in the Sasa-Satsuma equation on the continuous wave background

In this letter, via the Darboux transformation method we construct new analytic soliton solutions for the Sasa-Satsuma equation which describes the femtosecond pulses propagation in a monomode fiber. We reveal that two different types of femtosecond solitons, i.e., the anti-dark (AD) and Mexican-hat (MH) solitons, can form on a continuous wave (CW) background, and numerically study their stability under small initial perturbations. Different from the common bright and dark solitons, the AD and MH solitons can exhibit both the resonant and elastic interactions, as well as various partially/completely inelastic interactions which are composed of such two fundamental interactions. In addition, we find that the energy exchange between some interacting soliton and the CW background may lead to one AD soliton changing into an MH one, or one MH soliton into an AD one.Comment: 12 pages, 6 figure