Endovascular Stroke Treatment and Risk of Intracranial Hemorrhage in Anticoagulated Patients.

Background and Purpose- We aimed to determine the safety and mortality after mechanical thrombectomy in patients taking vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). Methods- In a multicenter observational cohort study, we used multiple logistic regression analysis to evaluate associations of symptomatic intracranial hemorrhage (sICH) with VKA or DOAC prescription before thrombectomy as compared with no anticoagulation. The primary outcomes were the rate of sICH and all-cause mortality at 90 days, incorporating sensitivity analysis regarding confirmed therapeutic anticoagulation. Additionally, we performed a systematic review and meta-analysis of literature on this topic. Results- Altogether, 1932 patients were included (VKA, n=222; DOAC, n=98; no anticoagulation, n=1612); median age, 74 years (interquartile range, 62-82); 49.6% women. VKA prescription was associated with increased odds for sICH and mortality (adjusted odds ratio [aOR], 2.55 [95% CI, 1.35-4.84] and 1.64 [95% CI, 1.09-2.47]) as compared with the control group, whereas no association with DOAC intake was observed (aOR, 0.98 [95% CI, 0.29-3.35] and 1.35 [95% CI, 0.72-2.53]). Sensitivity analyses considering only patients within the confirmed therapeutic anticoagulation range did not alter the findings. A study-level meta-analysis incorporating data from 7462 patients (855 VKAs, 318 DOACs, and 6289 controls) from 15 observational cohorts corroborated these observations, yielding an increased rate of sICH in VKA patients (aOR, 1.62 [95% CI, 1.22-2.17]) but not in DOAC patients (aOR, 1.03 [95% CI, 0.60-1.80]). Conclusions- Patients taking VKA have an increased risk of sICH and mortality after mechanical thrombectomy. The lower risk of sICH associated with DOAC may also be noticeable in the acute setting. Improved selection might be advisable in VKA-treated patients. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03496064. Systematic Review and Meta-Analysis: CRD42019127464

Argyrin B a non-competitive inhibitor of the human immunoproteasome exhibiting preference for β1i

Inhibitors of the proteasome have found broad therapeutic applications however, they show severe toxicity due to the abundance of proteasomes in healthy cells. In contrast, inhibitors of the immunoproteasome, which is upregulated during disease states, are less toxic and have increased therapeutic potential including against autoimmune disorders. In this project, we report argyrin B, a natural product cyclic peptide to be a reversible, non-competitive inhibitor of the immunoproteasome. Argyrin B showed selective inhibition of the β5i and β1i sites of the immunoproteasome over the β5c and β1c sites of the constitutive proteasome with nearly 20-fold selective inhibition of β1i over the homologous β1c. Molecular modelling attributes the β1i over β1c selectivity to the small hydrophobic S1 pocket of β1i and β5i over β5c to site-specific amino acid variations that enable additional bonding interactions and stabilization of the binding conformation. These findings facilitate the design of immunoproteasome selective and reversible inhibitors that may have a greater therapeutic potential and lower toxicity

P3HT-Based Solar Cells: Structural Properties and Photovoltaic Performance

Each year we are bombarded with B.Sc. and Ph.D. applications from students that want to improve the world. They have learned that their future depends on changing the type of fuel we use and that solar energy is our future. The hope and energy of these young people will transform future energy technologies, but it will not happen quickly. Organic photovoltaic devices are easy to sketch, but the materials, processing steps, and ways of measuring the properties of the materials are very complicated. It is not trivial to make a systematic measurement that will change the way other research groups think or practice. In approaching this chapter, we thought about what a new researcher would need to know about organic photovoltaic devices and materials in order to have a good start in the subject. Then, we simplified that to focus on what a new researcher would need to know about poly-3-hexylthiophene:phenyl-C61-butyric acid methyl ester blends (P3HT: PCBM) to make research progress with these materials. This chapter is by no means authoritative or a compendium of all things on P3HT:PCBM. We have selected to explain how the sample fabrication techniques lead to control of morphology and structural features and how these morphological features have specific optical and electronic consequences for organic photovoltaic device applications

Equilibrated charge carrier populations govern steady-state nongeminate recombination in disordered organic solar cells

\u3cp\u3eWe employed bias-assisted charge extraction techniques to investigate the transient and steady-state recombination of photogenerated charge carriers in complete devices of a disordered polymer-fullerene blend. Charge recombination is shown to be dispersive, with a significant slowdown of the recombination rate over time, consistent with the results from kinetic Monte Carlo simulations. Surprisingly, our experiments reveal little to no contributions from early time recombination of nonequilibrated charge carriers to the steady-state recombination properties. We conclude that energetic relaxation of photogenerated carriers outpaces any significant nongeminate recombination under application-relevant illumination conditions. With equilibrated charges dominating the steady-state recombination, quasi-equilibrium concepts appear suited for describing the open-circuit voltage of organic solar cells despite pronounced energetic disorder.\u3c/p\u3

Agricultural policy regime change assessment: Austrian accession to the European union

Policy regime change, Welfare analysis, Cointegration, Dynamic OLS, Hausman–Wu-Type test,

Reliability of charge carrier recombination data determined with charge extraction methods

Charge extraction methods are popular for measuring the charge carrier density in thin film organic solar cells and to draw conclusions about the order and coefficient of nongeminate charge recombination. However, results from such studies may be falsified by inhomogeneous steady state carrier profiles or surface recombination. Here, we present a detailed drift-diffusion study of two charge extraction methods, bias-assisted charge extraction (BACE) and time-delayed collection field (TDCF). Simulations are performed over a wide range of the relevant parameters. Our simulations reveal that both charge extraction methods provide reliable information about the recombination order and coefficient if the measurements are performed under appropriate conditions. However, results from BACE measurements may be easily affected by surface recombination, in particular for small active layer thicknesses and low illumination densities. TDCF, on the other hand, is more robust against surface recombination due to its transient nature but also because it allows for a homogeneous high carrier density to be inserted into the active layer. Therefore, TDCF is capable to provide meaningful information on the order and coefficient of recombination even if the model conditions are not exactly fulfilled. We demonstrate this for an only 100 nm thick layer of a highly efficient nonfullerene acceptor (NFA) blend, comprising the donor polymer PM6 and the NFA Y6. TDCF measurements were performed as a function of delay time for different laser fluences and bias conditions. The full set of data could be consistently fitted by a strict second order recombination process, with a bias- and fluence-independent bimolecular recombination coefficient k(2) = 1.7 x 10(-17)m(3) s(-1). BACE measurements performed on the very same layer yielded the identical result, despite the very different excitation conditions. This proves that recombination in this blend is mostly through processes in the bulk and that surface recombination is of minor importance despite the small active layer thickness. Published under license by AIP Publishing