Stochastic unraveling of Redfield master equations and its application to electron transfer problems

A method for stochastic unraveling of general time-local quantum master equations (QMEs) is proposed. The present kind of jump algorithm allows a numerically efficient treatment of QMEs which are not in Lindblad form, i.e. are not positive semidefinite by definition. The unraveling can be achieved by allowing for trajectories with negative weights. Such a property is necessary, e.g. to unravel the Redfield QME and to treat various related problems with high numerical efficiency. The method is successfully tested on the damped harmonic oscillator and on electron transfer models including one and two reaction coordinates. The obtained results are compared to those from a direct propagation of the reduced density matrix (RDM) as well as from the standard quantum jump method. Comparison of the numerical efficiency is performed considering both the population dynamics and the RDM in the Wigner phase space representation.Comment: accepted in J. Chem. Phys.; 26 pages, 6 figures; the order of authors' names on the title page correcte

Quantum Dot Potentials: Symanzik Scaling, Resurgent Expansions and Quantum Dynamics

This article is concerned with a special class of the ``double-well-like'' potentials that occur naturally in the analysis of finite quantum systems. Special attention is paid, in particular, to the so-called Fokker-Planck potential, which has a particular property: the perturbation series for the ground-state energy vanishes to all orders in the coupling parameter, but the actual ground-state energy is positive and dominated by instanton configurations of the form exp(-a/g), where a is the instanton action. The instanton effects are most naturally taken into account within the modified Bohr-Sommerfeld quantization conditions whose expansion leads to the generalized perturbative expansions (so-called resurgent expansions) for the energy values of the Fokker-Planck potential. Until now, these resurgent expansions have been mainly applied for small values of coupling parameter g, while much less attention has been paid to the strong-coupling regime. In this contribution, we compare the energy values, obtained by directly resumming generalized Bohr-Sommerfeld quantization conditions, to the strong-coupling expansion, for which we determine the first few expansion coefficients in powers of g^(-2/3). Detailed calculations are performed for a wide range of coupling parameters g and indicate a considerable overlap between the regions of validity of the weak-coupling resurgent series and of the strong-coupling expansion. Apart from the analysis of the energy spectrum of the Fokker-Planck Hamiltonian, we also briefly discuss the computation of its eigenfunctions. These eigenfunctions may be utilized for the numerical integration of the (single-particle) time-dependent Schroedinger equation and, hence, for studying the dynamical evolution of the wavepackets in the double-well-like potentials.Comment: 13 pages; RevTe

Preserving Derivative Information while Transforming Neuronal Curves

The international neuroscience community is building the first comprehensive atlases of brain cell types to understand how the brain functions from a higher resolution, and more integrated perspective than ever before. In order to build these atlases, subsets of neurons (e.g. serotonergic neurons, prefrontal cortical neurons etc.) are traced in individual brain samples by placing points along dendrites and axons. Then, the traces are mapped to common coordinate systems by transforming the positions of their points, which neglects how the transformation bends the line segments in between. In this work, we apply the theory of jets to describe how to preserve derivatives of neuron traces up to any order. We provide a framework to compute possible error introduced by standard mapping methods, which involves the Jacobian of the mapping transformation. We show how our first order method improves mapping accuracy in both simulated and real neuron traces under random diffeomorphisms. Our method is freely available in our open-source Python package brainlit

Development and implementation of blood pressure screening and referral guidelines for German community pharmacists

Involvement of community pharmacists in the detection and control of hypertension improves patient care. However, current European or North‐American guidelines do not provide specific guidance how to implement collaboration between pharmacists and physicians, especially when and how to refer patients with undetected or uncontrolled hypertension to a physician. The German Society of Cardiology and the ABDA – Federal Union of German Associations of Pharmacists developed and tested referral recommendations for community pharmacists, embedded in two guideline worksheets. The project included a guideline‐directed blood pressure (BP) measurement and recommendations when patients should be referred to their physician. A “red flag” referral within 4 weeks was recommended when SBP was >140 mm Hg or DBP >90 mm Hg (for subjects 160 mm Hg or >90 mm Hg (≥80 years) in undetected individuals, or >130 mm Hg or >80 mm Hg (140 mm Hg or >80 mm Hg (≥65 years) in treated patients. BP was measured in 187 individuals (86 with known hypertension, mean [±SD] age 62 ± 15 years, 64% female, and 101 without known hypertension, 47 ± 16 years, 75% female) from 17 community pharmacies. In patients with hypertension, poorly controlled BP was detected in 55% (n = 47) and were referred. A total of 16/101 subjects without a history of hypertension were referred to their physician because of uncontrolled BP. Structured BP testing in pharmacies identified a significant number of subjects with undetected/undiagnosed hypertension and patients with poorly controlled BP. Community pharmacists could play a significant role in collaboration with physicians to improve the management of hypertension

The ischiofemoral space of the hip is influenced by the frontal knee alignment

Purpose: The ischiofemoral distance (IFD), defined as the distance between the ischial tuberosity and the lesser trochanter of the femur, is gaining recognition as an extra-articular cause of hip pain. It is unknown whether the IFD is influenced by the frontal knee alignment. The aim of this study was to determine the influence of realignment surgery around the knee on the IFD. It was hypothesized that valgisation osteotomy around the knee is associated with reduction of the IFD. Methods: A consecutive series of 154 patients undergoing frontal realignment procedures around the knee in 2017 were included in this study. Long-leg standing radiographs were obtained before surgery and postoperatively. The IFD was measured between the ischium and the lesser trochanter at three different levels (proximal, middle and distal margins of the lesser trochanter parallel to the horizontal orientation of the pelvis) on standardized long-leg radiographs with the patient in upright standing position. The knee alignment was determined by measuring the hip knee ankle angle, mechanical lateral distal femur angle and the medial mechanical proximal tibia angle. Linear regression was performed to determine the influence of the change of frontal knee alignment on the IFD. Results: Linear regression showed a direct influence of the overall change in frontal knee alignment on the IFD of the hip, regardless of the site of the osteotomy (beta-0.4, confidence-interval - 0.5 to - 0.3, p < 0.001). Valgisation osteotomy around the knee induced a significant reduction of the ipsilateral IFD (p < 0.001), while varisation osteotomy induced a significant increase (p < 0.001). The amount of ISD change was 0.4 mm per corresponding degree of change in frontal knee alignment. Conclusion: These findings are relevant to both the hip and knee surgeons when planning an osteotomy or arthroplasty procedure. Correction of a malalignment of the knee may resolve an ischiofemoral conflict in the hip. The concept deserves inclusion in the diagnostic workup of both the hip and knee joints

final results of a noninterventional study

Background Data are limited regarding routine use of everolimus after initial vascular endothelial growth factor (VEGF)–targeted therapy. The aim of this prospective, noninterventional, observational study was to assess efficacy and safety of everolimus after initial VEGF-targeted treatment in patients with metastatic renal cell carcinoma (mRCC) in routine clinical settings. Methods Everolimus was administered per routine clinical practice. Patients with mRCC of any histology from 116 active sites in Germany were included. The main objective was to determine everolimus efficacy in time to progression (TTP). Progression-free survival (PFS), treatment duration, tumor response, adherence to everolimus regimen, treatment after everolimus, and safety were also assessed. Results In the total population (N = 334), median follow-up was 5.2 months (range, 0–32 months). Median treatment duration (safety population, n = 318) was 6.5 months (95% confidence interval [CI], 5–8 months). Median TTP and median PFS were similar in populations investigated. In patients who received everolimus as second-line treatment (n = 211), median (95% CI) TTP was 7.1 months (5–9 months) and median PFS was 6.9 months (5–9 months). Commonly reported adverse events (safety population, n = 318) were dyspnea (17%), anemia (15%), and fatigue (12%). Limitations of the noninterventional design should be considered. Conclusions This study reflects routine clinical use of everolimus in a large sample of patients with mRCC. Favorable efficacy and safety were seen for everolimus after previous therapy with one VEGF-targeted agent. Results of this study confirm everolimus as one of the standard options in second-line therapy for patients with mRCC. Novartis study code, CRAD001LD27: VFA registry for noninterventional studies (http://www.vfa.de/de/forschung/nisdb/ webcite)

Extension of in vivo half-life of biologically active molecules by XTEN protein polymers

AbstractXTEN™ is a class of unstructured hydrophilic, biodegradable protein polymers designed to increase the half-lives of therapeutic peptides and proteins. XTEN polymers and XTEN fusion proteins are typically expressed in Escherichia coli and purified by conventional protein chromatography as monodisperse polypeptides of exact length and sequence. Unstructured XTEN polypeptides have hydrodynamic volumes significantly larger than typical globular proteins of similar mass, thus imparting a bulking effect to the therapeutic payloads attached to them. Since their invention, XTEN polypeptides have been utilized to extend the half-lives of a variety of peptide- and protein-based therapeutics. Multiple clinical and preclinical studies and related drug discovery and development efforts are in progress. This review details the most current understanding of physicochemical properties and biological behavior of XTEN and XTENylated molecules. Additionally, the development path and status of several advanced drug discovery and development efforts are highlighted

Everolimus in metastatic renal cell carcinoma after failure of initial anti-VEGF therapy: final results of a noninterventional study

Background: Data are limited regarding routine use of everolimus after initial vascular endothelial growth factor (VEGF)-targeted therapy. The aim of this prospective, noninterventional, observational study was to assess efficacy and safety of everolimus after initial VEGF-targeted treatment in patients with metastatic renal cell carcinoma (mRCC) in routine clinical settings. Methods: Everolimus was administered per routine clinical practice. Patients with mRCC of any histology from 116 active sites in Germany were included. The main objective was to determine everolimus efficacy in time to progression (TTP). Progression-free survival (PFS), treatment duration, tumor response, adherence to everolimus regimen, treatment after everolimus, and safety were also assessed. Results: In the total population (N = 334),median follow-up was 5.2 months (range, 0-32 months). Median treatment duration (safety population, n = 318) was 6.5 months (95% confidence interval [CI], 5-8 months). Median TTP and median PFS were similar in populations investigated. In patients who received everolimus as second-line treatment (n = 211),median (95% CI) TTP was 7.1 months (5-9 months) and median PFS was 6.9 months (5-9 months). Commonly reported adverse events (safety population, n = 318) were dyspnea (17%),anemia (15%), and fatigue (12%). Limitations of the noninterventional design should be considered. Conclusions: This study reflects routine clinical use of everolimus in a large sample of patients with mRCC. Favorable efficacy and safety were seen for everolimus after previous therapy with one VEGF-targeted agent. Results of this study confirm everolimus as one of the standard options in second-line therapy for patients with mRCC

Index-antiguiding in narrow-ridge GaN-based laser diodes investigated by measurements of the current-dependent gain and index spectra and by self-consistent simulation

The threshold current density of narrow (1.5 {\mu}m) ridge-waveguide InGaN multi-quantum-well laser diodes, as well as the shape of their lateral far-field patterns, strongly depend on the etch depth of the ridge waveguide. Both effects can be attributed to strong index-antiguiding. A value of the antiguiding factor R = 10 is experimentally determined near threshold by measurements of the current-dependent gain and refractive index spectra. The device performances are simulated self-consistently solving the Schr\"odinger-Poisson equations and the equations for charge transport and waveguiding. Assuming a carrier-induced index change which matches the experimentally determined antiguiding factor, both the measured high threshold current and the shape of the far-field pattern of lasers with shallow ridges can be reproduced theoretically.Comment: This is an author-created, un-copyedited version of an article accepted for publication in the IEEE Journal of Quantum Electronics. IEEE is not responsible for any errors or omissions in this version of the manuscript or any version derived from i