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An effective primary treatment for obsessive-compulsive disorder (OCD) in children and adolescents as well as adults is exposure and response prevention (ERP), a form of intervention in the context of cognitive-behavioral therapy. Despite strong evidence supporting the efficacy and effectiveness of ERP from studies in research and real-world settings, its clinical use remains limited. This underuse is often attributed to access barriers such as the scarcity of properly trained therapists, geographical constraints, and costs. Some of these barriers may be addressed with virtual behavioral health, providing ERP for OCD through video teletherapy and supplemented by app-based therapeutic tools and messaging support between sessions. Studies of teletherapy ERP in adults with OCD have shown benefits in research and real-world settings in both small and large samples. However, studies of teletherapy ERP in children and adolescents thus far have been in small samples and limited to research rather than real-world settings. This study reports on the real-world effectiveness of teletherapy ERP for OCD in the largest sample (N=2173) of child and adolescent patients to date. Children and adolescents with OCD were treated with live, face-to-face video teletherapy sessions, with parent or caregiver involvement, using ERP. Assessments were conducted at baseline, after 7-11 weeks, and after 13-17 weeks. Additionally, longitudinal assessments of OCD symptoms were performed at weeks 18-30, 31-42, and 43-54. We analyzed longitudinal outcomes of OCD symptoms, depression, anxiety, and stress using linear mixed models. Treatment resulted in a median 38.46% (IQR 12.50%-64.00%) decrease in OCD symptoms at 13-17 weeks, and 53.4% of youth met full response criteria at this point. Improvements were observed in all categories of starting symptom severity: mild (median 40.3%, IQR 8.5%-79.8%), moderate (median 38.4%, IQR 13.3%-63.6%), and severe (median 34.1%, IQR 6.6%-58.5%). In addition, there were significant reductions in the severity of depression, anxiety, and stress symptoms. The median amount of therapist involvement was 13 (IQR 10.0-16.0) appointments and 11.5 (IQR 9.0-15.0) hours. Further, symptom improvements were maintained or improved upon in the longitudinal assessment periods of weeks 18-30, 31-42, and 43-54. These results show that remote ERP treatment, assisted by technology, can effectively improve both core OCD and related depression, anxiety, and stress symptoms in children and adolescents with OCD in a real-world setting. Notable outcomes were achieved in a relatively small amount of therapist time, demonstrating its efficiency. Demonstrating the usefulness of a delivery format that overcomes several traditional barriers to treatment, these findings have implications for widespread dissemination of accessible, evidence-based care for children and adolescents with OCD.

Exposure and response prevention, a type of cognitive-behavioral therapy, is an effective first-line treatment for obsessive-compulsive disorder (OCD). Despite extensive evidence of the efficacy of exposure and response prevention (ERP) from clinical studies and in real-world samples, it is still underused as a treatment. This is likely due to the limits to access to care that include the availability of adequately trained therapists, as well as geographical location, time, and cost barriers. To address these, NOCD created a digital behavioral health treatment for OCD using ERP delivered via video teletherapy and with technology-assisted elements including app-based therapy tools and between-session therapist messaging. We examined treatment outcomes in a large naturalistic sample of 3552 adults with a primary OCD diagnosis who received NOCD treatment. The treatment model consisted of twice-weekly, live, face-to-face video teletherapy ERP for 3 weeks, followed by 6 weeks of once-weekly brief video teletherapy check-ins for 30 minutes. Assessments were conducted at baseline, at midpoint after completion of 3 weeks of twice-weekly sessions, and at the end of 6 weeks of brief check-ins (endpoint). Longitudinal assessments were also obtained at 3, 6, 9, and 12 months after endpoint. Treatment resulted in clinically and statistically significant improvements, with a 43.4% mean reduction in obsessive-compulsive symptoms (g=1.0; 95% CI 0.93 to 1.03) and a 62.9% response rate. Treatment also resulted in a 44.2% mean reduction in depression, a 47.8% mean reduction in anxiety, and a 37.3% mean reduction in stress symptoms. Quality of life improved by a mean of 22.7%. Reduction in OCD symptoms and response rates were similar for those with mild, moderate, or severe symptoms. The mean duration of treatment was 11.5 (SD 4.0) weeks, and the mean total therapist time was 10.6 (SD 1.1) hours. Improvements were maintained at 3, 6, 9, and 12 months. In this sample, representing the largest reported treated cohort of patients with OCD to date, video teletherapy treatment demonstrated effectiveness in reducing obsessive-compulsive and comorbid symptoms and improved quality of life. Further, it achieved meaningful results in less than half the total therapist time compared with standard once-weekly outpatient treatment, an efficiency that represents substantial monetary and time savings. The effect size was large and similar to studies of in-person ERP. This technology-assisted remote treatment is readily accessible for patients, offering an advancement in the field in the dissemination of effective evidence-based care for OCD.

Exposure and response prevention (ERP) therapy, a form of cognitive-behavioral therapy, is a first-line, evidence-based treatment for obsessive-compulsive disorder (OCD) for adults and children. It is effective for the majority of those who engage in it, but treatment adherence can be challenging for some due to the stress involved in the treatment as well as different life circumstances that arise. To help improve treatment adherence, NOCD, a provider of video teletherapy ERP, identifies those at risk of non-adherence using a prediction algorithm trained on a data set of N  = 13,809 and provides targeted peer support interventions by individuals (“Member Advocates”) who successfully completed ERP treatment for OCD. Member Advocates, using lived OCD experience as well as experience with ERP, engage at-risk patients through digital messaging to engage, educate, and encourage patients in the early stages of treatment. From June 2022 to August 2022, N  = 815 patients deemed at risk were reached out to and n  = 251 responded and engaged with the Member Advocates. In the at-risk patients who engaged, the intervention resulted in a significant mean 30.4% more therapy hours completed compared to those who did not engage. Additionally, engaged patients had greater reductions in OCD severity. These results have implications for how data science, digital interventions, and strategic peer-to-peer communication and support can be combined to enhance the effectiveness of treatment.

Continuous-time derivative control and adaptive map-based recursive feedback control techniques are used to control chaos in a variety of systems and in situations that are of practical interest. The theoretical part of the research includes the review of fundamental concept of control theory in the context of its applications to deterministic chaotic systems, the development of a new adaptive algorithm to identify the linear system properties necessary for control, and the extension of the recursive proportional feedback control technique, RPF, to high dimensional systems. Chaos control was applied to models of a thermal pulsed combustor, electro-chemical dissolution and the hyperchaotic Rossler system. Important implications for combustion engineering were suggested by successful control of the model of the thermal pulsed combustor. The system was automatically tracked while maintaining control into regions of parameter and state space where no stable attractors exist. In a simulation of the electrochemical dissolution system, application of derivative control to stabilize a steady state, and adaptive RPF to stabilize a period one orbit, was demonstrated. The high dimensional adaptive control algorithm was applied in a simulation using the Rossler hyperchaotic system, where a period-two orbit with two unstable directions was stabilized and tracked over a wide range of a system parameter. In the experimental part, the electrochemical system was studied in parameter space, by scanning the applied potential and the frequency of the rotating copper disk. The automated control algorithm is demonstrated to be effective when applied to stabilize a period-one orbit in the experiment. We show the necessity of small random perturbations applied to the system in order to both learn the dynamics and control the system at the same time. The simultaneous learning and control capability is shown to be an important part of the active feedback control.

The Philadelphia chromosome is the result of a balanced reciprocal translocation between the long arms of chromosomes 9 and 22, resulting in the fusion gene BCR-ABL1. Despite it being a hallmark of acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML) and mixed-phenotype acute leukemia, comparatively little is known about its effects, which can be directly attributed to its presence in cancer cells. To study this question, we created and characterized a Jurkat cell line carrying this alteration via a CRISPR/Cas9-based approach. Compared with wild-type Jurkat cells, BCR-ABL1 p190-expressing cells exhibited increased proliferation and increased sensitivity to tyrosine kinase inhibitors (TKIs). By integrating gene expression, DNA methylation and protein expression data generated by next-generation sequencing (NGS) and mass spectrometry analyses, we identified a number of pathways as well as individual proteins that are altered in association with BCR-ABL1 p190. Among the deregulated proteins, we identified known cancer proteins, such as the tumor suppressors ASS1 and ABI3, which were downregulated in our model, or specifically upregulated TRBC1. Particularly noteworthy is the downregulation of CYP51A1, which is known to confer TKI resistance under normal circumstances, and therefore directly associated with increased TKI sensitivity in BCR-ABL1 p190-positive cells. Another interesting feature is SPART, whose abundance was increased despite strong promoter hypermethylation, indicating that some transcriptional changes in BCR-ABL1 p190-carrying cells occur independently of promoter methylation and reflect broader regulatory effects of the fusion.

The new multi-element alloying concept of systems with defined entropy (HEA — high-entropy alloy or MEA — medium-entropy alloy) is increasing in material research interest. Improved properties or combinations of properties are shown by several systems. Thus, the resulting microstructures and production of HEA/MEA as well as properties have been primarily investigated so far. Furthermore, processing is a key issue to transfer HEA/MEA systems to real components. Since welding is the most important joining process for metals, it is crucial to investigate the influence of welding to guarantee component integrity. Since most HEA are made of expensive alloying elements such as Co or Ni, they will not be used entirely as structural materials. Thus, it can be advantageous to weld conventional alloys such as austenitic stainless steels with the HEA and MEA to produce components that are both application-oriented and economically viable. Therefore, in this paper, first results of dissimilar metal welding, by tungsten inert gas (TIG) and friction stir welding (FSW), of a CoCrFeMnNi HEA as well as a CoCrNi MEA with a conventional AISI 304 austenitic stainless steel are presented. The focus is on the microstructure formation due to the two welding processes. The results of TIG welding show a dendritic microstructure, whereas in FSW both materials are stirred but still coexist.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and the total number of AF patients is constantly increasing. The mechanisms leading to and sustaining AF are not completely understood yet. Heterogeneities in atrial electrophysiology seem to play an important role in this context. Although some heterogeneities have been used in in-silico human atrial modeling studies, they have not been thoroughly investigated. In this study, the original electrophysiological (EP) models of Courtemanche et al., Nygren et al. and Maleckar et al. were adjusted to reproduce action potentials in 13 atrial regions. The parameter sets were validated against experimental action potential duration data and ECG data from patients with AV block. The use of the heterogeneous EP model led to a more synchronized repolarization sequence in a variety of 3D atrial anatomical models. Combination of the heterogeneous EP model with a model of persistent AF-remodeled electrophysiology led to a drastic change in cell electrophysiology. Simulated Ta-waves were significantly shorter under the remodeling. The heterogeneities in cell electrophysiology explain the previously observed Ta-wave effects. The results mark an important step toward the reliable simulation of the atrial repolarization sequence, give a deeper understanding of the mechanism of atrial repolarization and enable further clinical investigations.

Multi-Principal-Element or High-Entropy Alloys (MPEAs/HEAs) have gained increasing interest in the past two decades largely due to their outstanding properties such as superior mechanical strength and corrosion resistance. However, research studies on their processability are still scarce. This work assesses the effect of different machining conditions on the machinability of these novel alloys, with the objective of advancing the introduction of MPEA systems into industrial applications. The present study focuses on the experimental analysis of finish-milling conditions and their effects on the milling process and resulting surface finish of CoCrFeNi, Al[sub.0.3]CoCrFeNi and Al[sub.0.3]CoCrFeNiMo[sub.0.2] alloys fabricated via Spark Plasma Sintering. Ball-nose-end milling experiments have been carried out various milling parameters such as cutting speed, feed per cutting edge, and ultrasonic assistance. In situ measurements of cutting forces and temperature on the tool edge were performed during the experiments, and surface finish and tool wear were analyzed afterwards. The results exhibited decreasing cutting forces by means of low feed per cutting edge and reduced process temperatures at low cutting speed, with the use of ultrasonic-assisted milling. It was shown that the machinability of these modern alloys through conventional, as well as modern machining methods such as ultrasonic-assisted milling, is viable, and common theories in machining can be transferred to these novel MPEAs.

Multi-Principal-Element or High-Entropy Alloys (MPEAs/HEAs) have gained increasing interest in the past two decades largely due to their outstanding properties such as superior mechanical strength and corrosion resistance. However, research studies on their processability are still scarce. This work assesses the effect of different machining conditions on the machinability of these novel alloys, with the objective of advancing the introduction of MPEA systems into industrial applications. The present study focuses on the experimental analysis of finish-milling conditions and their effects on the milling process and resulting surface finish of CoCrFeNi, Al0.3CoCrFeNi and Al0.3CoCrFeNiMo0.2 alloys fabricated via Spark Plasma Sintering. Ball-nose-end milling experiments have been carried out various milling parameters such as cutting speed, feed per cutting edge, and ultrasonic assistance. In situ measurements of cutting forces and temperature on the tool edge were performed during the experiments, and surface finish and tool wear were analyzed afterwards. The results exhibited decreasing cutting forces by means of low feed per cutting edge and reduced process temperatures at low cutting speed, with the use of ultrasonic-assisted milling. It was shown that the machinability of these modern alloys through conventional, as well as modern machining methods such as ultrasonic-assisted milling, is viable, and common theories in machining can be transferred to these novel MPEAs.

In high-energy and astroparticle physics, event generators play an essential role, even in the simplest data analyses. As analysis techniques become more sophisticated, e.g. based on deep neural networks, their correct description of the observed event characteristics becomes even more important. Physical processes occurring in hadronic collisions are simulated within a Monte Carlo framework. A major challenge is the modeling of hadron dynamics at low momentum transfer, which includes the initial and final phases of every hadronic collision. QCD-inspired phenomenological models used for these phases cannot guarantee completeness or correctness over the full phase space. These models usually include parameters which must be tuned to suitable experimental data. Until now, event generators have been developed and tuned mainly on the basis of data from high-energy physics experiments at accelerators. The wealth of data available from the latest generation of astroparticle experiments has not yet been fully exploited, and in many cases is not satisfactorily described. Both kinds of data sets are complementary as astroparticle experiments provide sensitivity especially to hadrons produced nearly parallel to the collision axis and cover center-of-mass energies up to several hundred TeV, well beyond those reached at colliders so far. In this report, we provide an overview of state-of-the-art event generators and their tuning, including the most relevant inputs from high-energy accelerator and astroparticle experiments. We present a road map that shows, for the first time, how the unified tuning of event generators with accelerator-based and astroparticle data can be performed.