Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated with Psychopathology Across Independent Cohorts.

BACKGROUND: Early Psychosis patients (EP, within 3 years after psychosis onset) show significant variability, making outcome predictions challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, limiting the development of early interventions. METHODS: A data-driven approach, Partial Least Squares (PLS) correlation, was used across two independent datasets to examine multivariate relationships between white matter (WM) properties and symptomatology, to identify stable and generalizable signatures in EP. The primary cohort included EP patients from the Human Connectome Project-Early Psychosis (n=124). The replication cohort included EP patients from the Feinstein Institute for Medical Research (n=78). Both samples included individuals with schizophrenia, schizoaffective disorder, and psychotic mood disorders. RESULTS: In both cohorts, a significant latent component (LC) corresponded to a symptom profile combining negative symptoms, primarily diminished expression, with specific somatic symptoms. Both LCs captured comprehensive features of WM disruption, primarily a combination of subcortical and frontal association fibers. Strikingly, the PLS model trained on the primary cohort accurately predicted microstructural features and symptoms in the replication cohort. Findings were not driven by diagnosis, medication, or substance use. CONCLUSIONS: This data-driven transdiagnostic approach revealed a stable and replicable neurobiological signature of microstructural WM alterations in EP, across diagnoses and datasets, showing a strong covariance of these alterations with a unique profile of negative and somatic symptoms. This finding suggests the clinical utility of applying data-driven approaches to reveal symptom domains that share neurobiological underpinnings.

Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated with Psychopathology Across Independent Cohorts.

Background: Early Psychosis patients (EP, within 3 years after psychosis onset) show significant variability, making outcome predictions challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, limiting the development of early interventions. Methods: A data-driven approach, Partial Least Squares (PLS) correlation, was used across two independent datasets to examine multivariate relationships between white matter (WM) properties and symptomatology, to identify stable and generalizable signatures in EP. The primary cohort included EP patients from the Human Connectome Project-Early Psychosis (n=124). The replication cohort included EP patients from the Feinstein Institute for Medical Research (n=78). Both samples included individuals with schizophrenia, schizoaffective disorder, and psychotic mood disorders. Results: In both cohorts, a significant latent component (LC) corresponded to a symptom profile combining negative symptoms, primarily diminished expression, with specific somatic symptoms. Both LCs captured comprehensive features of WM disruption, primarily a combination of subcortical and frontal association fibers. Strikingly, the PLS model trained on the primary cohort accurately predicted microstructural features and symptoms in the replication cohort. Findings were not driven by diagnosis, medication, or substance use. Conclusions: This data-driven transdiagnostic approach revealed a stable and replicable neurobiological signature of microstructural WM alterations in EP, across diagnoses and datasets, showing a strong covariance of these alterations with a unique profile of negative and somatic symptoms. This finding suggests the clinical utility of applying data-driven approaches to reveal symptom domains that share neurobiological underpinnings.

Thiol-Ene Clickable Gelatin: A Platform Bioink for Multiple 3D Biofabrication Technologies.

Bioprinting can be defined as the art of combining materials and cells to fabricate designed, hierarchical 3D hybrid constructs. Suitable materials, so called bioinks, have to comply with challenging rheological processing demands and rapidly form a stable hydrogel postprinting in a cytocompatible manner. Gelatin is often adopted for this purpose, usually modified with (meth-)acryloyl functionalities for postfabrication curing by free radical photopolymerization, resulting in a hydrogel that is cross-linked via nondegradable polymer chains of uncontrolled length. The application of allylated gelatin (GelAGE) as a thiol-ene clickable bioink for distinct biofabrication applications is reported. Curing of this system occurs via dimerization and yields a network with flexible properties that offer a wider biofabrication window than (meth-)acryloyl chemistry, and without additional nondegradable components. An in-depth analysis of GelAGE synthesis is conducted, and standard UV-initiation is further compared with a recently described visible-light-initiator system for GelAGE hydrogel formation. It is demonstrated that GelAGE may serve as a platform bioink for several biofabrication technologies by fabricating constructs with high shape fidelity via lithography-based (digital light processing) 3D printing and extrusion-based 3D bioprinting, the latter supporting long-term viability postprinting of encapsulated chondrocytes.

Thermal Rayleigh-Marangoni convection in a three-layer liquid-metal-battery model.

The combined effects of buoyancy-driven Rayleigh-Bénard convection (RC) and surface tension-driven Marangoni convection (MC) are studied in a triple-layer configuration which serves as a simplified model for a liquid metal battery (LMB). The three-layer model consists of a liquid metal alloy cathode, a molten salt separation layer, and a liquid metal anode at the top. Convection is triggered by the temperature gradient between the hot electrolyte and the colder electrodes, which is a consequence of the release of resistive heat during operation. We present a linear stability analysis of the state of pure thermal conduction in combination with three-dimensional direct numerical simulations of the nonlinear turbulent evolution on the basis of a pseudospectral method. Five different modes of convection are identified in the configuration, which are partly coupled to each other: RC in the upper electrode, RC with internal heating in the molten salt layer, and MC at both interfaces between molten salt and electrode as well as anticonvection in the middle layer and lower electrode. The linear stability analysis confirms that the additional Marangoni effect in the present setup increases the growth rates of the linearly unstable modes, i.e., Marangoni and Rayleigh-Bénard instability act together in the molten salt layer. The critical Grashof and Marangoni numbers decrease with increasing middle layer thickness. The calculated thresholds for the onset of convection are found for realistic current densities of laboratory-sized LMBs. The global turbulent heat transfer follows scaling predictions for internally heated RC. The global turbulent momentum transfer is comparable with turbulent convection in the classical Rayleigh-Bénard case. In summary, our studies show that incorporating Marangoni effects generates smaller flow structures, alters the velocity magnitudes, and enhances the turbulent heat transfer across the triple-layer configuration.

Chemical convection in the methylene-blue-glucose system: Optimal perturbations and three-dimensional simulations.

A case of convection driven by chemical reactions is studied by linear stability theory and direct numerical simulations. In a plane aqueous layer of glucose, the methylene-blue-enabled catalytic oxidation of glucose produces heavier gluconic acid. As the oxygen is supplied through the top surface, the production of gluconic acid leads to an overturning instability. Our results complement earlier experimental and numerical work by Pons et al. First, we extend the model by including the top air layer with diffusive transport and Henry's law for the oxygen concentration at the interface to provide a more realistic oxygen boundary condition. Second, a linear stability analysis of the diffusive basic state in the layers is performed using an optimal perturbation approach. This method is appropriate for the unsteady basic state and determines the onset time of convection and the associated wavelength. Third, the nonlinear evolution is studied by the use of three-dimensional numerical simulations. Three typical parameters sets are explored in detail showing significant differences in pattern formation. One parameter set for which the flow is dominated by viscous forces, displays persistently growing convection cells. The other set with increased reaction rate displays a different flow regime marked by local chaotic plume emission. The simulated patterns are then compared to experimental observations.

Pattern formation and mass transfer under stationary solutal Marangoni instability.

According to the seminal theory by Sternling and Scriven, solutal Marangoni convection during mass transfer of surface-active solutes may occur as either oscillatory or stationary instability. With strong support of Manuel G. Velarde, a combined initiative of experimental works, in particular to mention those of Linde, Wierschem and coworkers, and theory has enabled a classification of dominant wave types of the oscillatory mode and their interactions. In this way a rather comprehensive understanding of the nonlinear evolution of the oscillatory instability could be achieved. A comparably advanced state-of-the-art with respect to the stationary counterpart seemed to be out of reach a short time ago. Recent developments on both the numerical and experimental side, in combination with assessing an extensive number of older experiments, now allow one to draw a more unified picture. By reviewing these works, we show that three main building blocks exist during the nonlinear evolution: roll cells, relaxation oscillations and relaxation oscillations waves. What is frequently called interfacial turbulence results from the interaction between these partly coexisting basic patterns which may additionally occur in different hierarchy levels. The second focus of this review lies on the practical importance of such convection patterns concerning their influence on mass transfer characteristics. Particular attention is paid here to the interaction between Marangoni and buoyancy effects which frequently complicates the pattern formation even more. To shed more light on these dependencies, new simulations regarding the limiting case of stabilizing density stratification and vanishing buoyancy are incorporated.

Patterned turbulence in liquid metal flow: computational reconstruction of the Hartmann experiment.

We present results of a numerical analysis of Hartmann's historical experiments on flows of mercury in pipes and ducts under the influence of magnetic fields. The computed critical parameters for the laminar-turbulent transition as well as the friction coefficients are in excellent agreement with Hartmann's data. The simulations provide a first detailed view of the flow structures that are experimentally inaccessible. Novel flow regimes with localized turbulent spots near the sidewalls parallel to the magnetic field and otherwise laminar flow are discovered. We finally suggest how these predictions can be tested in a transparent fluid using optical flow measurement.

Large-scale intermittency of liquid-metal channel flow in a magnetic field.

We predict a novel flow regime in liquid metals under the influence of a magnetic field. It is characterized by long periods of nearly steady, two-dimensional flow interrupted by violent three-dimensional bursts. Our prediction has been obtained from direct numerical simulations in a channel geometry at low magnetic Reynolds number and translates into physical parameters which are amenable to experimental verification under laboratory conditions. The new regime occurs in a wide range of parameters and may have implications for metallurgical applications.

Effect of excimer laser beam delivery and beam shaping on corneal sphericity in photorefractive keratectomy.

PURPOSE: To evaluate the impact of beam delivery and beam shaping on corneal profiles after myopic excimer laser photorefractive keratectomy (PRK). SETTING: Department of Ophthalmology, Charité-Campus Virchow Hospital, Humboldt University of Berlin, Berlin, Germany. METHODS: Standard myopic 193 nm excimer laser PRK of -3.0 diopters (D) and -6.0 D was performed in porcine eyes using 2 commercially available broad-beam lasers with band-mask and fractal-mask beam shaping, 2 flying-spot lasers, and a scanning-slit laser. A silicone replica was obtained to preserve the corneal profile and was measured with a dynamic focusing topometry system. RESULTS: The scanning-slit and flying-spot lasers created uniform profiles comparable to those in an untreated control group. Both broad-beam lasers with band-mask and fractal-mask beam shaping created central islands and paracentral profile valleys of 15.10 microm and 17.00 microm maximum height after -3.0 D PRK and 26.45 microm and 24.31 microm after -6.0 D PRK. An anti-central-island program, which applied a series of laser pulses centrally to compensate for the central profile elevations, did not eliminate the islands. Stromal surface roughness increased with ablation depth and was significantly worse after scanning-slit ablation than after broad-beam ablation. CONCLUSIONS: Laser-induced deviations from the intended uniform corneal profiles were associated with broad-beam ablation and increased ablation depth and therefore lessened the predictability of the refractive outcomes. Scanning-slit and flying-spot systems produced predictably uniform corneal profiles.

Oscillatory Rayleigh-Marangoni convection in a layer heated from above: numerical simulations with an undeformable free surface.

Joint action of buoyancy and thermocapillary forces can destabilize the motionless state in a liquid layer heated from above due to the coupling of internal and surface waves. The nonlinear evolution of this oscillatory instability is studied using three-dimensional direct numerical simulations with a pseudospectral Fourier-Chebyshev code. Alternating rolls and standing, oscillating squares are observed as final convective patterns. The flow is strongly localized near the free surface. Buoyancy plays a negligible role in kinetic energy production.

Low-dimensional chaos in zero-Prandtl-number Bénard-Marangoni convection.

Three-dimensional surface-tension-driven Bénard convection at zero Prandtl number is computed in the smallest possible doubly periodic rectangular domain that is compatible with the hexagonal flow structure at the linear stability threshold of the quiescent state. Upon increasing the Marangoni number beyond this threshold, the initially stationary flow becomes quickly time dependent. We investigate the transition to chaos for the case of a free-slip bottom wall by means of an analysis of the kinetic energy time series. We observe a period-doubling scenario for the transition to chaos of the energy attractor, intermittent behavior of a component of the mean velocity field, three characteristic energy levels, and two frequencies that contain a considerable amount of the power spectral density connected with the kinetic energy time series.