Oral Treprostinil is Associated with Improved Survival in FREEDOM-EV and its Open-Label Extension

\ua9 2023, The Author(s).Introduction: In the event-driven FREEDOM-EV trial, oral treprostinil delayed clinical worsening in patients with pulmonary arterial hypertension (PAH). Open-label extension studies offer additional data about tolerability, efficacy, and survival, especially for those initially assigned placebo. The aim of the current study was to determine if oral treprostinil changed survival when considering the parent and extension study, if treprostinil provides functional benefits for participants initially assigned to placebo, and if the benefits observed for those treated with treprostinil were durable. Methods: Both active and placebo participants from FREEDOM-EV could enroll in the FREEDOM-EV open-label extension (OLE) study after experiencing an investigator-assessed clinical worsening event or after parent study closure. All participants in the OLE were offered open-label oral treprostinil. Previously assigned placebo participants titrated to maximally tolerated doses; previously assigned treprostinil participants continued dose titration. We repeated assessments including functional class and 6-min walk distance (6MWD) at 12-week intervals and measured N-terminal pro-brain natriuretic peptide (NT-proBNP) at week 48. Survival was estimated by Kaplan–Meier analysis, and we estimated hazard ratio (HR) using Cox proportional hazards. Results: Of 690 FREEDOM-EV participants, 470 enrolled in the OLE; vital status was available for 89% of initial Freedom-EV participants. When considering the combined parent and open-label data, initial assignment to oral treprostinil reduced mortality (HR 0.64, 95% confidence interval 0.46–0.91, p = 0.013); absolute risk reduction was 9%. Participants randomized to placebo who initiated oral treprostinil after clinical worsening and tolerated treatment through week 48 demonstrated favorable shifts in functional class (p < 0.0001), 6MWD improvements of + 84 m (p < 0.0001), and a reduction in NT-proBNP of − 778 pg/mL (p = 0.02), compared to OLE baseline. Modest trends toward benefit were measured for those initially assigned placebo who did not have clinical worsening, and 132/144 (92%) of treprostinil assigned participants without clinical worsening remained on drug at week 48 in the OLE study. Adverse events were consistent with FREEDOM-EV. Conclusion: Initial treprostinil assignment improved survival in the entire data set; those who began treprostinil after a clinical worsening in the placebo arm and tolerated drug to week 48 enjoyed substantial functional gains. Clinical Trial Registration: ClinicalTrials.gov identifier NCT01560637

Hierarchical bismuth vanadate/reduced graphene oxide composite photocatalyst for hydrogen evolution and bisphenol A degradation

Bismuth vanadate (BiVO4) is a widely studied photocatalyst for the depollution of contaminated wastewater, production of hydrogen by water splitting, and organic synthesis. The photophysical properties of BiVO4 are sensitive to morphology and quantum confinement effects, and can exhibit enhanced photocatalytic performance in nanocomposites with graphene. Synthesis of hierarchical BiVO4 plates decorated by nanoparticles (h-BiVO4) in contact with reduced graphene oxide (RGO) is reported via a facile one-pot solution phase approach using ethanolamine and a polyethylene glycol stabilizer. The resulting h-BiVO4/RGO photocatalyst exhibited superior photoactivity for bisphenol A (BPA) degradation and hydrogen evolution under visible light irradiation compared to single component h-BiVO4 or a μm-sized block-like BiVO4 morphology. Rates of BPA photocatalytic degradation and apparent quantum efficiency (AQE) decreased in the order h-BiVO4/RGO (4.5 × 10−2 mmol.g−1.min−1; 15.1% AQE) > h-BiVO4 (3.5 × 10−2 mmol.g−1.min−1; 11.7% AQE) > BiVO4 (1 × 10−2 mmol.g−1.min−1; 3.4% AQE), representing a 4.5 fold enhancement for h-BiVO4/RGO versus BiVO4. Liquid phase photodegradation products included benzene-1,4-diol, cyclohexa-2,5-diene-1,4-dione and (2Z)-but-2-enedioic acid. The rate of photocatalytic hydrogen production under visible light was 11.5 µmol.g−1.h−1 for h-BiVO4/RGO, ~383.3 times greater than for BiVO4 (0.03µmol.g−1.h−1). The superior photocatalytic performance of h-BiVO4/RGO is largely attributed to its higher surface area, aided by enhanced visible light absorption and charge separation across the semiconductor-RGO interface, which together confer a higher density and lifetime of photoexcited charge carriers

Some applications of pipelining techniques in parallel scientific computing

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references: p. 46-47.Issued also on microfiche from Lange Micrographics.In this thesis, we study the applicability of pipelining techniques to the development of parallel algorithms for scientific computation. General principles for pipelining techniques are discussed and two applications, Gram-Schmidt orthogonalization and chasing algorithms, are considered. For each application, the pipelined parallel implementation is discussed and performance analysis is presented. For Gram-Schmidt orthogonalization, we investigate pipelined parallel algorithms based on various columnwise partitioning schemes. For chasing algorithms, in addition to the pipelining, we apply block-cyclic partitioning, group message-passing techniques to enhance the performance of the pipelined parallel algorithms. The numerical results for the use of these techniques are also presented and compared

Boundary element monotone iteration scheme for semilinear elliptic partial differential equations

Abstract. The monotone iteration scheme is a constructive method for solving a wide class of semilinear elliptic boundary value problems. With the availability of a supersolution and a subsolution, the iterates converge monotonically to one or two solutions of the nonlinear PDE. However, the rates of such monotone convergence cannot be determined in general. In addition, when the monotone iteration scheme is implemented numerically through the boundary element method, error estimates have not been analyzed in earlier studies. In this paper, we formulate a working assumption to obtain an exponentially fast rate of convergence. This allows a margin δ for the numerical implementation of boundary elements within the range of monotone convergence. We then interrelate several approximate solutions, and use the Aubin-Nitsche lemma and the triangle inequalities to derive error estimates for the Galerkin boundaryelement iterates with respect to the H r (Ω), 0 ≤ r ≤ 2, Sobolev space norms. Such estimates are of optimal order. Furthermore, as a peculiarity, we show that for the nonlinearities that are of separable type, “higher than optimal order ” error estimates can be obtained with respect to the mesh parameter h. Several examples of semilinear elliptic partial differential equations featuring different situations of existence/nonexistence, uniqueness/multiplicity and stability are discussed, computed, and the graphics of their numerical solutions are illustrated. 1

Through-wall yield collapse pressure of casing based on unified strength theory

The unified algorithm of through-wall yield collapse pressure for casing with due consideration of strength differential (SD), yield-to-tensile strength ratio, material hardening and intermediate principal stress, which is suitable to calculate collapse strength of all casing has been obtained based on unified strength theory, and four classical through-wall yield collapse formulas of casing have been presented based on the L. Von Mises, TRESCA, GM and twin yield strength criterion. The calculated value is maximum based on the twin yield strength criterion, which can be used as upper limit of through-wall yield collapse pressure, and the calculated value is minimum based on the TRESCA strength criterion, which can be used as lower limit of through-wall yield collapse pressure in the design process. Numerical and experimental comparisons show that the equation proposed by this paper is much closer to the collapse testing values than that of other equations. Key words: unified strength theory, casing collapse, through-wall yield, collapse pressure, strength differential, intermediate principal stres