Predicting change for individual psychotherapy clients on the basis of their nearest neighbors.

This study extended client-focused research by using the nearest neighbor (NN) approach, a client-specific sampling and prediction strategy derived from research on alpine avalanches. Psychotherapy clients (N = 203) seen in routine practice settings in the United Kingdom completed a battery of intake measures and then completed symptom intensity ratings before each session. Forecasts of each client's rate of change and session-by-session variability were computed on the basis of that client's NNs (n = 10-50 in different comparisons). Alternative forecasts used linear or log-linear slopes and were compared with an alternative prediction strategy. Results showed that the NN approach was superior to the alternative model in predicting rate of change, though the advantage was less clear for predicting variability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Coordination in networks: An economic equilibrium analysis

Networks utilizing modern communication technologies can offer competitive advantages to those using them wisely. But due to the existence of network effects, planning and operating cooperation networks is difficult. In this paper, the strategic situation of individual agents deciding on network participation is analysed. A systematic equilibrium analysis using computer-based simulations reveals principal solution scenarios for network agents and shows that network cooperation problems might frequently be not as difficult to resolve as often feared. In particular, strategic situations are identified showing that a majority of individuals might be better off getting the optimal solution from a central principal and that in many cases simple information intermediation can solve the start-up problem notorious in network economics.     

The Attentional Dynamics of Masked Detection.

A dichoptic masking procedure was used to test whether the mask-dependent cuing effects found in luminance detection by P. L. Smith (2000a) were due to integration masking or interruption masking. Attentional cuing enhanced detection sensitivity (d') when stimuli were backwardly masked with either dichoptic or monoptic masks, whereas no cuing effect was found with unmasked stimuli, implying the mask dependencies were due to interruption of stimulus processing in visual cortex by the mask. The effect is predicted by a gated diffusion process model in which masks interrupt stimulus processing and attention controls the flow of information to a sequential-sampling decision mechanism. The model correctly predicts different patterns of performance for detection and discrimination and cuing effects in simple reaction time. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pan-Lysyl Oxidase Inhibitor PXS-5505 Ameliorates Multiple-Organ Fibrosis by Inhibiting Collagen Crosslinks in Rodent Models of Systemic Sclerosis

Systemic sclerosis (SSc) is characterised by progressive multiple organ fibrosis leading to morbidity and mortality. Lysyl oxidases play a vital role in the cross-linking of collagens and subsequent build-up of fibrosis in the extracellular matrix. As such, their inhibition provides a novel treatment paradigm for SSc. A novel small molecule pan-lysyl oxidase inhibitor, PXS-5505, currently in clinical development for myelofibrosis treatment was evaluated using in vivo rodent models resembling the fibrotic conditions in SSc. Both lysyl oxidase and lysyl oxidase-like 2 (LOXL2) expression were elevated in the skin and lung of SSc patients. The oral application of PXS-5505 inhibited lysyl oxidase activity in the skin and LOXL2 activity in the lung. PXS-5505 exhibited anti-fibrotic effects in the SSc skin mouse model, reducing dermal thickness and α-smooth muscle actin. Similarly, in the bleomycin-induced mouse lung model, PXS-5505 reduced pulmonary fibrosis toward normal levels, mediated by its ability to normalise collagen/elastin crosslink formation. PXS-5505 also reduced fibrotic extent in models of the ischaemia-reperfusion heart, the unilateral ureteral obstruction kidney, and the CCl4-induced fibrotic liver. PXS-5505 consistently demonstrates potent anti-fibrotic efficacy in multiple models of organ fibrosis relevant to the pathogenesis of SSc, suggesting that it may be efficacious as a novel approach for treating SSc.     

Pyrazolonderivate. III. [2] Ein Beitrag zur Stereochemie von N,N-disubstituierten 4-Aminomethylen-3-methyl-1-phenyl-Δ2-pyrazolinonen-(5)

Pyrazolone Derivatives. III. A Contribution to Stereochemistry of N, N-Disubstituted 4-Aminomethylene-3-methyl-1-phenyl-Δ²-pyrazolinones-(5) The N,N-disubstituted 4-aminomethylene-Δ²-pyrazolinones-(5) 1 and 2 show a hindered internal rotation around the bond indicating a considerable polarisation of the system. This assumption is supported by i.r.-spectroscopic measurements which show that the CO-bond order decreases with increasing solvent polarity. Compounds 1 and 2 exist in the Z-configuration relative to the exocyclic CC-double bond. That can be attributed to a steric hindrance in the E-configuration of the aminomethylene-substituents with the methyl-group at the pyrazolone-ring.     

SARS-CoV-2 Infection Dysregulates Cilia and Basal Cell Homeostasis in the Respiratory Epithelium of Hamsters

Similar to many other respiratory viruses, SARS-CoV-2 targets the ciliated cells of the respiratory epithelium and compromises mucociliary clearance, thereby facilitating spread to the lungs and paving the way for secondary infections. A detailed understanding of mechanism involved in ciliary loss and subsequent regeneration is crucial to assess the possible long-term consequences of COVID-19. The aim of this study was to characterize the sequence of histological and ultrastructural changes observed in the ciliated epithelium during and after SARS-CoV-2 infection in the golden Syrian hamster model. We show that acute infection induces a severe, transient loss of cilia, which is, at least in part, caused by cilia internalization. Internalized cilia colocalize with membrane invaginations, facilitating virus entry into the cell. Infection also results in a progressive decline in cells expressing the regulator of ciliogenesis FOXJ1, which persists beyond virus clearance and the termination of inflammatory changes. Ciliary loss triggers the mobilization of p73⁺ and CK14⁺ basal cells, which ceases after regeneration of the cilia. Although ciliation is restored after two weeks despite the lack of FOXJ1, an increased frequency of cilia with ultrastructural alterations indicative of secondary ciliary dyskinesia is observed. In summary, the work provides new insights into SARS-CoV-2 pathogenesis and expands our understanding of virally induced damage to defense mechanisms in the conducting airways.     

Enabling Coarse X-ray Fluorescence Imaging Scans with Enlarged Synchrotron Beam by Means of Mosaic Crystal Defocusing Optics

Trace elements, functionalized nanoparticles and labeled entities can be localized with sub-mm spatial resolution by X-ray fluorescence imaging (XFI). Here, small animals are raster scanned with a pencil-like synchrotron beam of high energy and low divergence and the X-ray fluorescence is recorded with an energy-dispersive detector. The ability to first perform coarse scans to identify regions of interest, followed by a close-up with a sub-mm X-ray beam is desirable, because overall measurement time and X-ray dose absorbed by the (biological) specimen can thus be minimized. However, the size of X-ray beams at synchrotron beamlines is usually strongly dependent on the actual beamline setup and can only be adapted within specific pre-defined limits. Especially, large synchrotron beams are non-trivial to generate. Here, we present the concept of graphite-based, convex reflection optics for the one-dimensional enlargement of a 1 mm wide synchrotron beam by a factor of 5 to 10 within a 1 m distance. Four different optics are tested and characterized and their reflection properties compared to ray tracing simulations. The general shape and size of the measured reflection profiles agree with expectations. Enhancements with respect to homogeneity and efficiency can be expected with improved optics manufacturing. A mouse phantom is used for a proof-of-principle XFI experiment demonstrating the applicability of coarse and fine scans with the suggested optics design.