FSSH-2: Fewest Switches Surface Hopping with Robust Switching Probability.

This study introduces the FSSH-2 scheme, a redefined and numerically stable adiabatic Fewest Switches Surface Hopping (FSSH) method for mixed quantum-classical dynamics. It reformulates the standard FSSH hopping probability without using nonadiabatic coupling vectors and allows for numerical time integration with larger step sizes. The advantages of FSSH-2 are demonstrated by numerical experiments for five different model systems in one and two spatial dimensions with up to three electronic states.

WaveTrain: A Python package for numerical quantum mechanics of chain-like systems based on tensor trains.

WaveTrain is an open-source software for numerical simulations of chain-like quantum systems with nearest-neighbor (NN) interactions only. The Python package is centered around tensor train (TT, or matrix product) format representations of Hamiltonian operators and (stationary or time-evolving) state vectors. It builds on the Python tensor train toolbox Scikit_tt, which provides efficient construction methods and storage schemes for the TT format. Its solvers for eigenvalue problems and linear differential equations are used in WaveTrain for the time-independent and time-dependent Schrödinger equations, respectively. Employing efficient decompositions to construct low-rank representations, the tensor-train ranks of state vectors are often found to depend only marginally on the chain length N. This results in the computational effort growing only slightly more than linearly with N, thus mitigating the curse of dimensionality. As a complement to the classes for full quantum mechanics, WaveTrain also contains classes for fully classical and mixed quantum-classical (Ehrenfest or mean field) dynamics of bipartite systems. The graphical capabilities allow visualization of quantum dynamics "on the fly," with a choice of several different representations based on reduced density matrices. Even though developed for treating quasi-one-dimensional excitonic energy transport in molecular solids or conjugated organic polymers, including coupling to phonons, WaveTrain can be used for any kind of chain-like quantum systems, with or without periodic boundary conditions and with NN interactions only. The present work describes version 1.0 of our WaveTrain software, based on version 1.2 of scikit_tt, both of which are freely available from the GitHub platform where they will also be further developed. Moreover, WaveTrain is mirrored at SourceForge, within the framework of the WavePacket project for numerical quantum dynamics. Worked-out demonstration examples with complete input and output, including animated graphics, are available.

Solving the time-independent Schrödinger equation for chains of coupled excitons and phonons using tensor trains.

We demonstrate how to apply the tensor-train format to solve the time-independent Schrödinger equation for quasi-one-dimensional excitonic chain systems with and without periodic boundary conditions. The coupled excitons and phonons are modeled by Fröhlich-Holstein type Hamiltonians with on-site and nearest-neighbor interactions only. We reduce the memory consumption as well as the computational costs significantly by employing efficient decompositions to construct low-rank tensor-train representations, thus mitigating the curse of dimensionality. In order to compute also higher quantum states, we introduce an approach that directly incorporates the Wielandt deflation technique into the alternating linear scheme for the solution of eigenproblems. Besides systems with coupled excitons and phonons, we also investigate uncoupled problems for which (semi-)analytical results exist. There, we find that in the case of homogeneous systems, the tensor-train ranks of state vectors only marginally depend on the chain length, which results in a linear growth of the storage consumption. However, the central processing unit time increases slightly faster with the chain length than the storage consumption because the alternating linear scheme adopted in our work requires more iterations to achieve convergence for longer chains and a given rank. Finally, we demonstrate that the tensor-train approach to the quantum treatment of coupled excitons and phonons makes it possible to directly tackle the phenomenon of mutual self-trapping. We are able to confirm the main results of the Davydov theory, i.e., the dependence of the wave packet width and the corresponding stabilization energy on the exciton-phonon coupling strength, although only for a certain range of that parameter. In future work, our approach will allow calculations also beyond the validity regime of that theory and/or beyond the restrictions of the Fröhlich-Holstein type Hamiltonians.

Effectiveness of a mindfulness- and skill-based health-promoting leadership intervention on supervisor and employee levels: A quasi-experimental multisite field study.

Acknowledging increasing demands for workforce health, new theoretical concepts of health-oriented leadership (HoL) have been introduced, emphasizing the supervisor's direct and explicit engagement in workplace health by focusing on their self- and staff-care. However, empirical evidence of the effectiveness of HoL interventions for supervisors and their staff is still scarce. We developed a mindfulness- and skill-based HoL intervention and investigated its effectiveness in a quasi-experimental multisite field study including supervisor and employee ratings from 12 German companies. A total of n = 117 supervisors and their employees (n = 744) completed assessments on mental distress and perceived HoL before and after the intervention as well as during the 3-month follow-up period. The intervention group was compared to a passive control cohort based on propensity score matching. Hierarchical linear models showed that the supervisors who had participated in the HoL intervention experienced a significantly larger decrease in mental distress and an increase in health-oriented self-care as well as staff-care than did their matched controls (g = 0.18-0.59). These results were confirmed by intent-to-treat analyses. The effect on supervisors' mental distress was mediated by an increase of their health-oriented self-care and moderated by the frequency of their mindfulness practice. No significant effects appeared between groups regarding outcomes at the employee level. Overall, these findings indicate how HoL can be effectively trained to increase supervisors' self- and staff-care and reduce their mental distress. Future research should explore additional moderator variables, linkages to established work stress models, and improvements of these interventions to increase their effectiveness for employees. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The SALT-Readout ASIC for Silicon Strip Sensors of Upstream Tracker in the Upgraded LHCb Experiment.

SALT, a new dedicated readout Application Specific Integrated Circuit (ASIC) for the Upstream Tracker, a new silicon detector in the Large Hadron Collider beauty (LHCb) experiment, has been designed and developed. It is a 128-channel chip using an innovative architecture comprising a low-power analogue front-end with fast pulse shaping and a 40 MSps 6-bit Analog-to-Digital Converter (ADC) in each channel, followed by a Digital Signal Processing (DSP) block performing pedestal and Mean Common Mode (MCM) subtraction and zero suppression. The prototypes of SALT were fabricated and tested, confirming the full chip functionality and fulfilling the specifications. A signal-to-noise ratio of about 20 is achieved for a silicon sensor with a 12 pF input capacitance. In this paper, the SALT architecture and measurements of the chip performance are presented.

Fate of pendimethalin in soil and characterization of non-extractable residues (NER).

One important route of degradation of herbicide pendimethalin in soil leads to formation of non-extractable residues (NER). To investigate NER nature (irreversibly, chemically bound, including possible biogenic NER, or strongly sorbed and entrapped) residues of 14C-labelled pendimethalin in soil were investigated after conventional extraction with organic solvents by silylation. After 400 days of incubation, 32.0% of applied radioactivity (AR) was transformed into NER, 39.9% AR remained extractable. Mineralization reached 26.2% AR. Additionally, 14C-pendimethalin was incubated in soil amended with compost for 217 days to investigate the influence of organic amendments on NER formation. NER amounted to 37.8% AR, with 57.9% AR remaining extractable. Mineralization was negligible (1.4% AR). For all sampling times only low amounts of radioactivity were entrapped (<5% AR) in soil without compost amendment. Pendimethalin was present only in trace amounts (ca. 0.4% AR), other released residues consisted of undefined fractions (sum ≈2% AR). In soil amended with compost, silylation overall resulted in release of higher amounts of radioactivity (19% AR). Addition of compost led to an increase in potential entrapment and sorption sites for pendimethalin, forming higher amounts of strongly sorbed, entrapped residues. Furthermore, potential release of non-extractable pendimethalin residues was investigated by incubation of solvent-extracted soil (without compost amendment) mixed with fresh soil for additional 3 months. NER were partly mineralized (7% AR) and 20% became extractable with organic solvents. However, no pendimethalin or any known metabolites were found. It can be concluded that no parent pendimethalin was found and NER of pendimethalin in soil are mainly formed by covalent binding to organic matrix with only low potential of remobilization under natural conditions.

Efficacy of universal preoperative decolonization with Polyhexanide in primary joint arthroplasty on surgical site infections. A multicenter before-and after-study.

BACKGROUND: Surgical site infections (SSI) are rare but severe complications after total joint arthroplasty (TJA). Decolonization measures prior to elective orthopedic surgeries have shown to reduce the risk of SSI with Staphylococcus aureus (S. aureus). OBJECTIVE: To determine the efficacy of universal decolonization with Polyhexanide on SSI rates with a focus on Staphylococcus aureus in patients with TJA. METHODS: Patients scheduled for elective hip or knee TJA in 5 participating certified orthopedic centers were included between 2015 and 2018 into this before and after study. Data on patients, surgeries and infections were prospectively collected. CDC-criteria were used to define and categorize Infections within 90 days after surgery. From January 2017 on, patients received decolonization sets containing Polyhexanide. Patients performed a 5 day decolonization regimen starting 4 days prior to surgery which included wipes, nasal decontamination and oral solution. RESULTS: Thirteen thousand, three hundred fifteen patients received TJA. During intervention 4437 decolonization sets were distributed among 7175 patients. Overall SSI rates increased from 0.68 /100 surgeries to 0.91/ 100 surgeries after implementation of the intervention (IRR 1.32; 95% CI 0.90-1.96). Time series analysis identified an increasing trend of SSI prior to the intervention. After implementation overall SSI rates plateaued. Regression analysis revealed surgery during intervention period to be an independent risk factor for developing a SSI (OR 1.34; 95%CI 1.18-1.53). Initial SSI rates due to S. aureus were 0.24/100 surgeries and decreased to 0.14/100 surgeries (IRR 0.57; 95% CI 0.25-1.22) after introduction of decolonization. Regression analysis revealed surgery during intervention period to be an independent protective factor for developing a SSI with S. aureus (OR 0.57, 95% CI: 0.33-0.99). Overall deep S. aureus SSI decreased significantly from 0.22/100 surgeries to 0.00/100 surgeries in patients adherent to protocol (IRR 0.00, 95% CI 0.00-.85). CONCLUSION: Universal decolonization with Polyhexanide did not reduce overall surgical site infections, but was effective in reducing Staphylococcus aureus - surgical site infections following elective joint arthroplasty. Polyhexanide could extend the list of alternatives to already established decolonization strategies. TRIAL REGISTRATION: The trial was registered at the German Registry for clinical studies www.drks.de ( DRKS00011505 ).

Real-world non-interventional long-term post-authorisation safety study of ruxolitinib in myelofibrosis.

Primary objective of this non-interventional, post-authorisation safety study was to provide real-world safety data [incidence of adverse drug reactions (ADRs)/serious adverse events (SAEs)] on adult patients with myelofibrosis exposed/or not exposed to ruxolitinib. Key secondary objectives included the incidence/outcome of events of special interest (bleeding events, serious/opportunistic infections, second primary malignancies, and deaths). Overall, 462 patients were included [prevalent users = 260, new users = 32, non-exposed = 170 (inclusive of ruxolitinib-switch, n = 57)]. The exposure-adjusted incidence rates (per 100 patient-years) of ADRs (19·3 vs. 19·6) and SAEs (25·2 vs. 25·0) were comparable amongst new-users versus prevalent-users cohorts, respectively; most frequent ADRs across all cohorts included thrombocytopenia, anaemia, epistaxis, urinary tract infection, and herpes zoster. Anaemia, pneumonia, general physical health deterioration, sepsis, and death were the most frequent SAEs across all cohorts. Incidence rates of bleeding events (21·6) and serious/opportunistic infections (34·5) were higher in ruxolitinib-switch cohort versus other cohorts. The incidence rate of second primary malignancies was higher in the prevalent-users cohort (10·1) versus other cohorts. The observed safety profile of ruxolitinib in the present study along with the safety findings from the COMFORT/JUMP/EXPAND studies support the use of ruxolitinib for long-term treatment of patients with myelofibrosis.

Health-Oriented Leadership and Mental Health From Supervisor and Employee Perspectives: A Multilevel and Multisource Approach.

The link between leadership and mental health at the workplace is well established by prior research. However, most of the studies have addressed this relationship from a single-source perspective. The aim of this study was to examine how supervisor and employee ratings of health-oriented leadership correspond to each other and which sources are predictive for employee mental health. We assessed data within 99 teams (headed by 99 supervisors) containing 713 employees in 11 different companies in Southern Germany. Supervisors and their staff completed questionnaires on the supervisors' health-oriented staff-care dimensions awareness, value of health and health behavior (Health-Oriented Leadership Scale, HoL) and current mental distress (Hospital Anxiety and Depression Scale, HADS). Hierarchical linear models revealed that supervisors' self-ratings were significantly related to their employees' ratings (at the team level) only on the health behavior dimension, but not on the health awareness and value of health dimensions. Also, supervisors rated themselves significantly higher on HoL compared to their employees. Employee ratings of HoL significantly predicted their own level of mental distress (direct within-level effect), whereas supervisor ratings of HoL did not predict employees' mental distress at the team level (direct cross-level effect). Supervisors' self-ratings of HoL did not influence the relationship between employee ratings of HoL and their mental distress on an individual level (cross-level interaction). These results highlight the complex relationship between multisource assessments of HoL and employee mental health, emphasizing the importance of subjective perception for mental health. Future studies should investigate under which conditions supervisor and employee ratings correspond to each other and are predictive for mental health at the workplace.

Inhibition of PLK1 by capped-dose volasertib exerts substantial efficacy in MDS and sAML while sparing healthy haematopoiesis.

INTRODUCTION: Targeting the cell cycle machinery represents a rational therapeutic approach in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (sAML). Despite substantial response rates, clinical use of the PLK inhibitor volasertib has been hampered by elevated side effects such as neutropenia and infections. OBJECTIVES: The primary objective was to analyse whether a reduced dose of volasertib was able to limit toxic effects on the healthy haematopoiesis while retaining its therapeutic effect. METHODS: Bone marrow mononuclear cells (BMMNCs) of patients with MDS/sAML (n = 73) and healthy controls (n = 28) were treated with volasertib (1 µM to 1 nM) or vehicle control. Short-term viability analysis was performed by flow cytometry after 72 hours. For long-term viability analysis, colony-forming capacity was assessed after 14 days. Protein expression of RIPK3 and MCL-1 was quantified via flow cytometry. RESULTS: Reduced dose levels of volasertib retained high cell death-inducing efficacy in primary human stem and progenitor cells of MDS/sAML patients without affecting healthy haematopoiesis in vitro. Interestingly, volasertib reduced colony-forming capacity and cell survival independent of clinical stage or mutational status. CONCLUSIONS: Volasertib offers a promising therapeutic approach in patients with adverse prognostic profile. RIPK3 and MCL-1 might be potential biomarkers for sensitivity to volasertib treatment.

OH defect contents in quartz in a granitic system at 1-5 kbar.

Quartz is able to incorporate trace elements (e.g., H, Li, Al, B) depending on the formation conditions (P, T, and chemical system). Consequently, quartz can be used as a tracer for petrogenetic information of silicic plutonic bodies. In this experimental study, we provide the first data set on the OH defect incorporation in quartz from granites over a pressure/temperature range realistic for the emplacement of granitic melts in the upper crust. Piston cylinder and internally heated pressure vessel synthesis experiments were performed in a water-saturated granitic system at 1-5 kbar and 700-950 °C. Crystals from successful runs were analysed by secondary ion mass spectrometry (SIMS) and Fourier transform infrared (FTIR) spectroscopy, and their homogeneity was verified by FTIR imaging. IR absorption bands can be assigned to specific OH defects and analysed qualitatively and quantitatively and reveal that (1) the AlOH band triplet at 3310, 3378 and 3430 cm-1 is the dominating absorption feature in all spectra, (2) no simple trend of total OH defect incorporation with pressure can be observed, (3) the LiOH defect band at 3470-3480 cm-1 increases strongly in a narrow pressure interval from 4 kbar (220 µg/g H2O) to 4.5 kbar (500 µg/g H2O), and declines equally strong towards 5 kbar (180 µg/g H2O). Proton incorporation is charge balanced according to the equation H+ + A+ + P5+ = M3+ + B3+, with A+ = alkali ions and M3+ = trivalent metal ions.

WavePacket: A Matlab package for numerical quantum dynamics. III. Quantum-classical simulations and surface hopping trajectories.

WavePacket is an open-source program package for numerical simulations in quantum dynamics. Building on the previous Part I (Schmidt and Lorenz, Comput. Phys. Commun. 2017, 213, 223] and Part II (Schmidt and Hartmann, Comput. Phys. Commun. 2018, 228, 229] which dealt with quantum dynamics of closed and open systems, respectively, the present Part III adds fully classical and mixed quantum-classical propagation techniques to WavePacket. There classical phase-space densities are sampled by trajectories which follow (diabatic or adiabatic) potential energy surfaces. In the vicinity of (genuine or avoided) intersections of those surfaces, trajectories may switch between them. To model these transitions, two classes of stochastic algorithms have been implemented: (1) Tully's fewest switches surface hopping and (2) Landau-Zener-based single switch surface hopping. The latter one offers the advantage of being based on adiabatic energy gaps only, thus not requiring nonadiabatic coupling information any more. The present work describes the MATLAB version of WavePacket 6.1.0, which is essentially an object-oriented rewrite of previous versions, allowing to perform fully classical, quantum-classical and quantum-mechanical simulations on an equal footing, that is, for the same physical system described by the same WavePacket input. The software package is hosted and further developed at the Sourceforge platform, where also extensive Wiki-documentation as well as numerous worked-out demonstration examples with animated graphics are available. © 2019 Wiley Periodicals, Inc.

Replica exchange MD simulations of two-dimensional water in graphene nanocapillaries: rhombic versus square structures, proton ordering, and phase transitions.

The hydrogen bond patterns, proton ordering, and phase transitions of monolayer ice in two-dimensional hydrophobic confinement are fundamentally different from those found for bulk ice. To investigate the behavior of quasi-2D ice, we perform molecular dynamics simulations of water confined between fixed graphene plates at a distance of 0.65 nm. While experimental results are still limited and theoretical investigations are often based on a single, often empirically based force field model, this work presents a systematic study modeling the water-graphene interaction by effective Lennard-Jones potentials previously derived from high-level ab initio CCSD(T) calculations of water adsorbed on graphene [Phys. Chem. Chem. Phys., 2013, 15, 4995]. For the water-water interaction different water force fields, i.e. SPCE, TIP3P, TIP4P, TIP4P/ICE, and TIP5P, are used. The water occupancy of the graphene capillary at a pressure of 1000 MPa is determined to be between 13.5 and 13.9 water molecules per square nanometer, depending on the choice of the water force field. Based on these densities, we explore the structure and dynamics of quasi-2D water for temperatures ranging from 200 K to about 600 K for each of the five force fields. To ensure complete sampling of the configurational space and to overcome the barriers separating metastable structures, these simulations are based on the replica exchange molecular dynamics technique. We report different tetragonal hydrogen bond patterns, which are classified as nearly square or as rhombic. While many of these arrangements are essentially flat, in some cases puckered arrangements are found, too. Also the proton ordering of the quasi-2D water structures is considered, allowing us to identify them as ferroelectric, ferrielectric or antiferroelectric. For temperatures between 200 K and 400 K we find several second-order phase transitions from one ice structure to another, changing in many cases both the arrangements of the oxygen atoms and the proton ordering. For temperatures between 400 K and 600 K there are melting-like transitions from a monolayer of ice to a monolayer of liquid water. These first-order phase transitions have a latent heat between 3.4 and 4.0 kJ mol-1. Both the values of the transition temperatures and of the latent heats display considerable model dependence for the five different water models investigated here.

Cost effectiveness of lifelong therapy with PCSK9 inhibitors for lowering cardiovascular events in patients with stable coronary artery disease: Insights from the Ludwigshafen Risk and Cardiovascular Health cohort.

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduce cardiovascular events in coronary artery disease (CAD). Their costs exceed that of established oral lipid-lowering agents. Previous cost-effectiveness assessments have been inconsistent. Markov cohort state transitions models for stable CAD patients were calculated using information from 1530 participants of the Ludwigshafen Risk and Cardiovascular Health Study (LURIC) with known causes of deaths. Non-fatal to fatal event rates, drug prices, direct treatment costs, and utility weights were from public sources. At an assumed relative risk reduction of 32.5% and an annual drug price of 8500 Euros, QALYs gained were 1.23 and 1.20, savings were 2390 and 2410 Euros, and ICERs were 112,530 and 108,660 Euros in women and men, respectively. When the annual cost of this medication was set at 1600 Euros, corresponding ICERs were 21,180 and 20,450 Euros. PCSK9i treatment is cost-effective in stable CAD at a threshold of 150,000 Euro and annual costs of 8500 Euros. As the broad use of PCSK9i therapy in CAD would have a disruptive impact on the healthcare budget, treatment should be focused on very high risk patients (≥3 comorbidities, annual risk of 10%); alternatively, and for lower risk, significant cost reductions would be needed.

Transformational Leadership and Depressive Symptoms in Germany: Validation of a Short Transformational Leadership Scale.

OBJECTIVES: The objective of the present study was to validate a shortened transformational leadership (TL) scale (12 items) comprising core TL behaviour and to test the associations of this shortened TL scale with depressive symptoms. METHODS: The study used cross-sectional data from 1632 employees of the overall workforce of a middle-sized German company (51.6% men; mean age, 41.35 years; standard deviation, 9.4 years). TL was assessed with the German version of the Transformational Leadership Inventory and depressive symptoms with the Hospital Anxiety and Depression Scale (HADS). The structural validity of the core TL scale was assessed with confirmatory factor analysis. Associations with depressive symptoms were estimated with structural equation modelling and adjusted logistic regression. RESULTS: Confirmatory factor analysis and structural equation modelling showed better model fit for the core TL than for the full TL score. Logistic regression revealed 3.61-fold (95% confidence interval [CI], 2.20 to 5.93: women) to 4.46-fold (95% CI, 2.86 to 6.95: men) increased odds of reporting depressive symptoms (HADS score >8) for those in the lowest tertile of reported core TL. CONCLUSIONS: The shortened core TL seems to be a valid instrument for research and training purposes in the context of TL and depressive symptoms in employees. Of particular note, men reporting poor TL were more likely to report depressive symptoms.

Venetoclax with azacitidine targets refractory MDS but spares healthy hematopoiesis at tailored dose.

Patients with Myelodysplastic Syndromes (MDS) and secondary Acute Myeloid Leukemia (sAML) have a very poor prognosis after failure of hypomethylating agents (HMA). Stem cell transplantation is the only effective salvage therapy, for which only a limited number of patients are eligible due to age and comorbidity. Combination therapy of venetoclax and azacitidine (5-AZA) seems to be a promising approach in myeloid malignancies, but data from patients with HMA failure are lacking. Furthermore, a considerable concern of combination regimens in elderly AML and MDS patients is the toxicity on the remaining healthy hematopoiesis. Here, we report in vitro data showing the impact of venetoclax and 5-AZA, alone or in combination, in a larger cohort of MDS/sAML patients (n = 21), even after HMA failure (n = 13). We especially focused on the effects on healthy hematopoiesis and the impact on colony forming capacity as a parameter for long-term effects. To the best of our knowledge, we show for the first time that venetoclax in combination with capped dose of 5-AZA targets cell malignancies, while sparing healthy hematopoiesis.

A Comparison of Job Stress Models: Associations With Employee Well-Being, Absenteeism, Presenteeism, and Resulting Costs.

OBJECTIVE: This study investigates the associations between Effort-Reward-Imbalance (ERI), Overcommitment (OC), Job-Demand-Control (JDC), and Organizational Injustice (OIJ) with employee well-being, absenteeism, and presenteeism, as well as the costs incurred. METHODS: Cross-sectional data from 1440 German pharmaceutical company employees assessing job stress, employee well-being, absenteeism, and presenteeism were used. Linear regression and interval regression analyses assessed separate and independent associations and sample-specific costs were estimated. RESULTS: All four stressors were related to employee well-being, presenteeism, and absenteeism when analyzed separately. OIJ showed the strongest independent association with absenteeism (coef. = 0.89; P < 0.01), whereas OC was most strongly independently associated with lower well-being (coef. = -0.44; P < 0.01) and higher presenteeism (coef. = 0.28; P < 0.01). Absenteeism costs per employee/year were higher than presenteeism costs. CONCLUSIONS: Occupational health interventions reducing job stress will have strong potential for productivity raise and lower costs.