The Effect of Block Ownership on Future Firm Value and Performance

This paper examines the performance of the investment decisions of block owners. The block ownership data is obtained from Dlugosz, Fahlenbrach, Gompers, and Metrick (2006). We find that firm valuation (measured by Tobin's Q), operating performance (measured by changes in return on assets) and stock performance (measured by excess buy and hold returns) are positively and significantly related to the previous years' level of block ownership both in terms of the size of the ownership and the number of blockholders. Our results are robust to endogeneity concerns. Regarding whether a specific blockholder is an “insider” or an “outsider” to the firm, we find that the ownership of “outside” blockholders is a key determinant in explaining future firm performance. Note though that this category makes up about two-thirds of the aggregate amount of blockholding in Dlugosz et al. (2006) database, and also includes all blockholders not classified in other categories. In general, we attribute the superior performance to the presence of more blockholders. We also find an inverse association between the volatility in blockownership and the ex-post firm performance measures

Clinical impact of double protease inhibitor boosting with Lopinavir/Ritonavir and Amprenavir as part of salvage antiretroviral therapy

Purpose: Double protease inhibitor (PI) boosting is being explored as a new strategy in salvage antiretroviral (ARV) therapy. However, if a negative drug interaction leads to decreased drug levels of either or both PIs, double PI boosting could lead to decreased virologic response. A negative drug interaction has been described between amprenavir (APV) and lopinavir/ritonavir (LPV/r). This observational cohort study assessed the virologic impact of the addition of APV to a salvage ARV regimen, which also contains LPV/r, compared to a regimen containing LPV/r alone. Method: Patients initiated on a salvage ARV regimen that included LPV/r obtained from the expanded access program in Toronto, Canada, were evaluated. APV (600-1,200 mg bid) was added at the discretion of the treating physician. Results: Using multivariate Cox proportional hazards models, we found that the addition of APV to a LPV/r-containing salvage regimen was not significantly associated with time to virologic suppression (< 50 copies/mL; adjusted hazard ratio [HR] = 0.75, p = .12) or with time to virologic rebound (adjusted HR = 1.46, p = .34). Those patients who received higher doses of APV had an increased chance of virologic suppression (p = .03). In a subset of 27 patients, the median LPV Ctrough was significantly lower in patients receiving APV (p = .04), and the median APV Ctrough was reduced compared to reported controls. Conclusion: Our data do not support an additional benefit in virologic reduction of double boosting with APV and LPV/r relative to LPV/r alone in salvage ARV therapy. Our study's limitations include its retrospective nature and the imbalance between the two groups potentially confounding the results. Although these factors were adjusted for in the multivariate analysis, a prospective randomized controlled trial is warranted to confirm our findings

Contemplations on Dirac's equation in quaternionic coordinates

A formulation of Dirac's equation using complex-quaternionic coordinates appears to yield an enormous gain in formal elegance, as there is no longer any need to invoke Dirac matrices. This formulation, however, entails several peculiarities, which we investigate and attempt to interpret

A prospective cohort study of the effects of adjuvant breast cancer chemotherapy on taste function, food liking, appetite and associated nutritional outcomes

\u27Taste\u27 changes are commonly reported during chemotherapy. It is unclear to what extent this relates to actual changes in taste function or to changes in appetite and food liking and how these changes affect dietary intake and nutritional status

Application of hot melt extrusion for improving bioavailability of artemisinin a thermolabile drug

Hot melt extrusion has been used to produce a solid dispersion of the thermolabile drug artemisinin. Formulation and process conditions were optimized prior to evaluation of dissolution and biopharmaceutical performance. Soluplus®, a low Tg amphiphilic polymer especially designed for solid dispersions enabled melt extrusion at 110 °C although some drug-polymer incompatibility was observed. Addition of 5% citric acid as a pH modifier was found to suppress the degradation. The area under plasma concentration time curve (AUC0–24h) and peak plasma concentration (Cmax) were four times higher for the modified solid dispersion compared to that of pure artemisinin

Coarse-grained modeling study of nonpeptide RGD ligand density and PEG molecular weight on the conformation of poly(γ-glutamyl-glutamate) paclitaxel conjugates

Molecular shape, flexibility, and surface hydrophilicity are thought to influence the ability of nanoparticles to cross biological barriers during drug delivery. In this study, coarse-grained (CG) molecular dynamics (MD) simulations were used to study these properties of a polymer-drug construct in potential clinical development: poly(γ-glutamyl-glutamate)-paclitaxel-poly(ethylene glycol) nonpeptide RGD (PGG-PTX-PEG-npRGD), a linear glutamyl-glutamate polymer with paclitaxel and poly(ethylene glycol)-nonpeptide RGD side groups. It was hypothesized that the PEG molecular weight (MW) (500 Da; 1,000 Da; and 2,000 Da) and nonpeptide RGD ligand density (4, 8, 12, and 16 per molecule), respectively, may have advantageous effects on the shape, flexibility, and surface hydrophilicity of PGG-PTX-PEG-npRGD. Circular dichroism spectroscopy was used to suggest initial structures for the all-atom (AA) models of PGG-PTX-PEG-npRGD, which were further converted to CG models using a commercially available mapping algorithm. Due to its semi-flexibility, PGG-PTX-PEG-npRGD is not limited to one specific conformation. Thus, CG MD simulations were run until statistical equilibrium, at which PGG-PTX-PEG-npRGD is represented as an ensemble of statistically similar conformations. The size of a PGG-PTX-PEG-npRGD molecule is not affected by the PEG MW or the nonpeptide RGD density, but higher PEG MW results in increased surface density of a PGG-PTX-PEG-npRGD molecule. Most PGG-PTX-PEG-npRGD shapes are globular, although filamentous shapes were also observed in the PEG500 and PEG1000 molecules. PEG500 and PEG1000 molecules are more flexible than PEG2000 systems. A higher presence of npRGD ligands results in decrease surface hydrophilicity of PGG-PTX-PEG-npRGD. These results indicate that the PGG-PTX-PEG1000-npRGD4 and PGG-PTX-PEG1000-npRGD8 molecules are the most efficacious candidates and are further recommended for experimental preclinical studies

The Stratonovich formulation of quantum feedback network rules

We express the rules for forming quantum feedback networks using the Stratonovich form of quantum stochastic calculus rather than the Ito, or SLH form. Remarkably the feedback reduction rule implies that we obtain the Schur complement of the matrix of Stratonovich coupling operators where we short out the internal input/output coefficients.Comment: 14 pages, 6 figures (The Stratonovich form of the Series Product added in the revision.