Late Cardiotoxicity from the Tyrosine Kinase Inhibitor, Dasatinib: Pleural Effusions, Pulmonary Arterial Hypertension, and Right Heart Failure

Despite the remarkable progress made over the past few decades in the management of patients with both solid and hematologic malignancies, radiation- and chemotherapy-related cardiotoxicity remains an ongoing problem. This is true even for newer highly targeted therapies, including tyrosine kinase inhibitors (TKIs). This report presents a case of late/severe right heart dysfunction secondary to pulmonary hypertension, developed after ten years of therapy with dasatinib. We also review the history of this known, but often unrecognized, and potentially reversible complication, and we suggest treatment options. Additionally, this case highlights the remarkable effectiveness of TKIs in patients with chronic myelogenous leukemia while also emphasizing the ever-present concern that even in the absence of clinical or laboratory evidence of residual leukemic disease, discontinuing chemotherapeutic agents may result in prompt recrudescence and death

Valid Asymptotic Expansions for the Maximum Likelihood Estimator of the Parameter of a Stationary, Gaussian, Strongly Dependent Process

We establish the validity of an Edgeworth expansion to the distribution of the maximum likelihood estimator of the parameter of a stationary, Gaussian, strongly dependent process. The result covers ARFIMA type models, including fractional Gaussian noise. The method of proof consists of three main ingredients: (i) verification of a suitably modified version of Durbin's (1980) general conditions for the validity of the Edgeworth expansion to the joint density of the log-likelihood derivatives; (ii) appeal to a simple result of Skovgaard (1986) to obtain from this an Edgeworth expansion for the joint distribution of the log-likelihood derivatives; (iii) appeal to and extension of arguments of Bhattacharya and Ghosh (1978) to accomplish the passage from the result on the log-likelihood derivatives to the result for the maximum likelihood estimators. We develop and make extensive use of a uniform version of Dahlhaus's (1989) Theorem 5.1 on products of Toeplitz matrices; the extension of Dahlhaus's result is of interest in its own right. A small numerical study of the efficacy of the Edgeworth expansion is presented for the case of fractional Gaussian noise.Edgeworth expansions, long memory processes, ARFIMA models

A topological realization of the congruence subgroup Kernel A

A number of years ago, Kumar Murty pointed out to me that the computation of the fundamental group of a Hilbert modular surface ([7],IV,${\S}$6), and the computation of the congruence subgroup kernel of SL(2) ([6]) were surprisingly similar. We puzzled over this, in particular over the role of elementary matrices in both computations. We formulated a very general result on the fundamental group of a Satake compactification of a locally symmetric space. This lead to our joint paper [1] with Lizhen Ji and Les Saper on these fundamental groups. Although the results in it were intriguingly similar to the corresponding calculations of the congruence subgroup kernel of the underlying algebraic group in [5], we were not able to demonstrate a direct connection (cf. [1], ${\S}$7). The purpose of this note is to explain such a connection. A covering space is constructed from inverse limits of reductive Borel-Serre compactifications. The congruence subgroup kernel then appears as the group of deck transformations of this covering. The key to this is the computation of the fundamental group in [1]

Supersymmetric Brane World Scenarios from Off-Shell Supergravity

Using N=2 off-shell supergravity in five dimensions, we supersymmetrize the brane world scenario of Randall and Sundrum. We extend their construction to include supersymmetric matter at the fixpoints.Comment: 15 pages, no figures, late

Lp-cohomology of negatively curved manifolds

We compute the $L^p$-cohomology spaces of some negatively curved manifolds. We deal with two cases: manifolds with finite volume and sufficiently pinched negative curvature, and conformally compact manifolds