Patient groups prone to polypharmacy and special subpopulations are susceptible to suboptimal treatment. Refined dosing in special populations is imperative to improve therapeutic response and/or ...lowering the risk of toxicity. Model‐informed precision dosing (MIPD) may improve treatment outcomes by achieving the optimal dose for an individual patient. There is, however, relatively little published evidence of large‐scale utility and impact of MIPD, where it is often implemented as local collaborative efforts between academia and healthcare. This article highlights some successful applications of bringing MIPD to clinical care and proposes strategies for wider integration in healthcare. Considerations are brought up herein that will need addressing to see MIPD become “widespread clinical practice,” among those, wider interdisciplinary collaborations and the necessity for further evidence‐based efficacy and cost–benefit analysis of MIPD in healthcare. The implications of MIPD on regulatory policies and pharmaceutical development are also discussed as part of the roadmap.
The effects of atomic-scale etch pits, anisotropic etching, and surface steps on the lineshape of the Si–H stretch vibration are studied using realistic kinetic Monte Carlo simulations of etched ...Si(111) surfaces. All three morphological features lead to a red shift in the in-phase vibrational mode, which is due to decreased dynamic dipole coupling. Pitted surfaces have an asymmetrically broadened vibrational lineshape because the decreased symmetry lends oscillator strength to higher-order vibrational modes. A much smaller asymmetry is seen in spectra of anisotropically etched surfaces. Previous estimates of the perfection of NH
4F-etched Si(111) surfaces, which were based on infra-red lineshape measurements, are shown to overestimate the quality of the etched surfaces.
Intersystem Crossing in Charge-Transfer Excited States Gould, Ian R; Boiani, James A; Gaillard, Elizabeth B ...
The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory,
05/2003, Volume:
107, Issue:
18
Journal Article
Peer reviewed
Absolute rate constants for intersystem crossing (ISC) in exciplexes formed between cyanoanthracenes as acceptors and alkylbenzenes as donors in solvents with low to moderate polarity have been ...measured. The extent of charge transfer in these particular exciplexes has been determined previously, and thus the dependence of the ISC rate constant on this parameter is obtained. A smooth transition of exciplexes with high locally excited state character to those with essentially pure charge-transfer character argues in favor of a mechanism of intersystem crossing involving a spin-forbidden return electron transfer process to form the locally excited triplet directly. The proposed mechanism is supported by the observed energy gap dependence of the rate constant, and by deuterium isotope effects. External heavy-atom effects in chlorinated solvents are observed. Analysis of the rate constant for intersystem crossing for the pure charge-transfer exciplexes using electron-transfer theory allows determination of the matrix element for the spin-forbidden electron-transfer reaction. It is found to be roughly 3000 times smaller than the matrix element for corresponding spin-allowed electron transfer in similar systems. General principles for the factors that control the mechanisms of intersystem crossing in excited charge-transfer states are discussed.
An updated, Web-based tool compares available analytical methods for environmental monitoring projects. A related tool provides information for emergency situations.
The scope of FDA's jurisdiction over laboratory-developed tests (LDTs), and whether FDA has such jurisdiction at all, has been a heavily debated issue over the past several years. If FDA moves ...forward with its guidance, or Congress takes action to reform LDT and IVD regulation, a fundamental question that needs to be answered is how to divide activities regulated by FDCA from those regulated by CLIA. In this article, we consider FDA's authority to regulate LDTs and the policy implications of regulation, and discuss an idea for a fact-driven framework to distinguish FDCA- and CLIA- activities.
Independent scientific achievements have led to the discovery of aberrant splicing patterns in oncogenesis, while more recent advances have uncovered novel gene fusions involving neurotrophic ...tyrosine receptor kinases (NTRKs) in gliomas. The exploration of NTRK splice variants in normal and neoplastic brain provides an intersection of these two rapidly evolving fields. Tropomyosin receptor kinase B (TrkB), encoded NTRK2, is known for critical roles in neuronal survival, differentiation, molecular properties associated with memory, and exhibits intricate splicing patterns and post-translational modifications. Here, we show a role for a truncated NTRK2 splice variant, TrkB.T1, in human glioma. TrkB.T1 enhances PDGF-driven gliomas in vivo, augments PDGF-induced Akt and STAT3 signaling in vitro, while next generation sequencing broadly implicates TrkB.T1 in the PI3K signaling cascades in a ligand-independent fashion. These TrkB.T1 findings highlight the importance of expanding upon whole gene and gene fusion analyses to include splice variants in basic and translational neuro-oncology research.
PDF
