The molecular genetics and cellular mechanisms underlying pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is an incurable disorder clinically characterised by a sustained elevation of mean arterial pressure in the absence of systemic involvement. As the adult circulation is a low pressure, low resistance system, PAH represents a reversal to a foetal state. The small pulmonary arteries of patients exhibit luminal occlusion resultant from the uncontrolled growth of endothelial and smooth muscle cells. This vascular remodelling is comprised of hallmark defects, most notably the plexiform lesion. PAH may be familial in nature but the majority of patients present with spontaneous disease or PAH associated with other complications. In this paper, the molecular genetic basis of the disorder is discussed in detail ranging from the original identification of the major genetic contributant to PAH and moving on to current next-generation technologies that have led to the rapid identification of additional genetic risk factors. The impact of identified mutations on the cell is examined, particularly, the determination of pathways disrupted in disease and critical to pulmonary vascular maintenance. Finally, the application of research in this area to the design and development of novel treatment options for patients is addressed along with the future directions PAH research is progressing towards

Dollars and Performance: Treating Alcohol Misuse in Maine

If public funds are allocated efficiently, then an increase in funding should improve the performance of substance abuse treatment programs. In the data used in this paper, performance (measured as abstinence rates) and expenditures per patient are not positively correlated. One explanation is that funding is endogeneous, i.e. programs treating more difficult patients receive more funding. The data comes from all Maine´s outp/atient drug-free programs that received public funding between 1991 and 1994. After controlling for endogeneity, this paper concludes that the marginal impact of expenditures per patient on abstinence rates is small and statistically insignificantly different from zero.Publicad

A consistent estimator for the binomial distribution in the presence of "incidental parameters": an application to patent data

In this paper a consistent estimator for the Binomial distribution in the presence of incidental parameters, or fixed effects, when the underlying probability is a logistic function is derived. The consistent estimator is obtained from the maximization of a conditional likelihood function in light of Andersen's work. Monte Carlo simulations show its superiority relative to the traditional maximum likelihood estimator with fixed effects also in small samples, particularly when the number of observations in each cross-section, T, is small. Finally, this new estimator is applied to an original dataset that allows the estimation of the probability of obtaining a patent

Substance abuse treatment: what do we know? an economist's perspective

The substance abuse treatment literature has basically dealt with four important questions: 1) Is treatment effective? 2) Are all programs equally effective? 3) why do programs differ in their effectiveness? and 4) which treatments are most cost-effective?. This paper reviews the substance abuse literature around these four questions

Boolean decomposition for AIG optimization

Restructuring techniques for And-Inverter Graphs (AIG), such as rewriting and refactoring, are powerful, scalable and fast, achieving highly optimized AIGs after few iterations. However, these techniques are biased by the original AIG structure and limited by single output optimizations. This paper investigates AIG optimization for area, exploring how far Boolean methods can reduce AIG nodes through local optimization.Boolean division is applied for multi-output functions using two-literal divisors and Boolean decomposition is introduced as a method for AIG optimization. Multi-output blocks are extracted from the AIG and optimized, achieving a further AIG node reduction of 7.76% on average for ITC99 and MCNC benchmarks.Peer ReviewedPostprint (author's final draft

From local to critical fluctuations in lattice models: a non-perturbative renormalization-group approach

We propose a modification of the non-perturbative renormalization-group (NPRG) which applies to lattice models. Contrary to the usual NPRG approach where the initial condition of the RG flow is the mean-field solution, the lattice NPRG uses the (local) limit of decoupled sites as the (initial) reference system. In the long-distance limit, it is equivalent to the usual NPRG formulation and therefore yields identical results for the critical properties. We discuss both a lattice field theory defined on a $d$-dimensional hypercubic lattice and classical spin systems. The simplest approximation, the local potential approximation, is sufficient to obtain the critical temperature and the magnetization of the 3D Ising, XY and Heisenberg models to an accuracy of the order of one percent. We show how the local potential approximation can be improved to include a non-zero anomalous dimension $\eta$ and discuss the Berezinskii-Kosterlitz-Thouless transition of the 2D XY model on a square lattice.Comment: v1) 12 pages, 12 figures. v2) Revised version. v3) Improved figure