We construct an automaton group with a PSPACE-complete word problem, proving a conjecture due to Steinberg. Additionally, the constructed group has a provably more difficult, namely ...EXPSPACE-complete, compressed word problem and acts over a binary alphabet. Thus, it is optimal in terms of the alphabet size. Our construction directly simulates the computation of a Turing machine in an automaton group and, therefore, seems to be quite versatile. It combines two ideas: the first one is a construction used by D’Angeli, Rodaro and the first author to obtain an inverse automaton semigroup with a PSPACE-complete word problem and the second one is to utilize a construction used by Barrington to simulate Boolean circuits of bounded degree and logarithmic depth in the group of even permutations over five elements.
Abstract Objective Krabbe disease (KD) is a multisystem neurodegenerative disorder with severe disability and premature death, mostly with an infancy/childhood onset. In rare cases of late‐onset ...phenotypes, symptoms are often milder and difficult to diagnose. We here present a translational approach combining diagnostic and biochemical analyses of a male patient with a progressive gait disorder starting at the age of 44 years, with a final diagnosis of late‐onset KD (LOKD). Methods Additionally to cerebral MRI, protein structural analyses of the β‐galactocerebrosidase protein (GALC) were performed. Moreover, expression, lysosomal localization, and activities of β‐glucocerebrosidase (GCase), cathepsin B (CTSB), and cathepsin D (CTSD) were analyzed in leukocytes, fibroblasts, and lysosomes of fibroblasts. Results Exome sequencing revealed biallelic likely pathogenic variants: GALC exons 11–17: 33 kb deletion; exon 4: missense variant (c.334A>G, p.Thr112Ala). We detected a reduced GALC activity in leukocytes and fibroblasts. While histological KD phenotypes were absent in fibroblasts, they showed a significantly decreased activities of GCase, CTSB, and CTSD in lysosomal fractions, while expression levels were unaffected. Interpretation The presented LOKD case underlines the age‐dependent appearance of a mildly pathogenic GALC variant and its interplay with other lysosomal proteins. As GALC malfunction results in reduced ceramide levels, we assume this to be causative for the here described decrease in CTSB and CTSD activity, potentially leading to diminished GCase activity. Hence, we emphasize the importance of a functional interplay between the lysosomal enzymes GALC, CTSB, CTSD, and GCase, as well as between their substrates, and propose their conjoined contribution in KD pathology.
Studies have shown that certain Internet interventions can help alleviate depression. However, many such interventions contain personal support elements, making it difficult to ascertain whether the ...program or the support drives the effects. Studies are needed to investigate whether Internet interventions contribute to symptom reduction even when they are delivered without personal support, and even among severely depressed individuals who often receive other forms of treatment.
This randomized controlled trial aimed to examine the effect of an Internet intervention that was deployed without personal support (“Deprexis”) among adults with initially severe depression symptoms.
Adults recruited from a range of sources who had exceeded the threshold for severe depression (PHQ-9≥15) in a pre-screening assessment and met inclusion criteria were randomized (N=163) to the intervention (3months program access; n=78) or care-as-usual/waitlist control (n=85). A diagnostic screening interview was administered by telephone at baseline to all participants. Online assessments were administered at baseline, 3months (post-treatment), and 6months (follow-up). The main outcome was the Patient Health Questionnaire (PHQ-9) between baseline and post-treatment.
Eighty-two percent of randomized participants were reached for the post-treatment assessment. Results for the intention-to-treat (ITT) sample showed significant intervention effects on depression reduction between baseline and post-treatment (linear mixed model MM, F1,155.6=9.00, p<.01, for the time by condition interaction), with a medium between-group effect size, Cohen's d=0.57 (95% CI: 0.22–0.92). Group differences in depression severity at follow-up were marginally significant in the ITT sample, t (119)=1.83, p=0.07, and smaller than at post-treatment (PHQ-9, d=0.33, 95% CI: −0.03–0.69). The number needed to treat (NNT) at post-treatment was 5, with 38% of participants in the intervention group achieving response (at least 50% PHQ-9 symptom change, plus post-treatment score <10), compared to 17% in the control group, p<0.01. Effects on secondary outcomes, including anxiety, health-related quality of life, and somatic symptoms, were not significant, with the exception of significant effects on anxiety reduction in PP analyses. Early ratings of program helpfulness/alliance (after 3weeks) predicted pre–post depression reduction, controlling for baseline severity and early symptom change.
These results replicate and extend previous findings by showing that Deprexis can facilitate symptomatic improvement over 3months and, perhaps to a lesser degree, up until 6months among adults with initially severe depression.
Zusammenfassung
Bei stetig steigenden Primärimplantationszahlen und Revisionen von Schulterprothesen in Deutschland sind konsekutiv steigende Inzidenzen von periprothetischen Frakturen und ...Infektionen zu erwarten. Klinisch präsentieren sich Patienten häufig mit einem reduzierten Bewegungsausmaß und schmerzhaftem Schultergelenk im Sinne einer sog. Low-grade-Infektion mit
Cutibacterium acnes
als Haupterreger. Das International Consensus Meeting on Orthopedic Infections 2018 etablierte die erste Definition einer periprothetischen Schulterinfektion. Als diagnostischer Marker eignet sich primär das C‑reaktive Protein, ggf. in Kombination mit D‑Dimeren. Goldstandard für die Bestimmung einer periprothetischen Infektion ist nach wie vor die arthroskopische oder offene Probengewinnung mit ergänzender Histopathologie. In den kommenden Jahren wird sich zeigen, ob das sog. „Next Generation Sequencing“ (NGS) zur Identifikation von polymikrobiellen Infektionen in den diagnostischen Algorithmus Einzug finden wird.
Abstract
Nonresponse in panel studies can lead to a substantial loss in data quality owing to its potential to introduce bias and distort survey estimates. Recent work investigates the usage of ...machine learning to predict nonresponse in advance, such that predicted nonresponse propensities can be used to inform the data collection process. However, predicting nonresponse in panel studies requires accounting for the longitudinal data structure in terms of model building, tuning, and evaluation. This study proposes a longitudinal framework for predicting nonresponse with machine learning and multiple panel waves and illustrates its application. With respect to model building, this approach utilizes information from multiple waves by introducing features that aggregate previous (non)response patterns. Concerning model tuning and evaluation, temporal crossvalidation is employed by iterating through pairs of panel waves such that the training and test sets move in time. Implementing this approach with data from a German probability-based mixed-mode panel shows that aggregating information over multiple panel waves can be used to build prediction models with competitive and robust performance over all test waves.
Lattice Boltzmann methods are a promising approach for the numerical solution of fluid-dynamic problems. We consider the one-dimensional Goldstein-Taylor model with the aim to answer some of the ...questions concerning the numerical analysis of lattice Boltzmann schemes. Discretizations for the solution of the heat equation are presented for a selection of boundary conditions. Stability and convergence of the solutions are proved by employing energy estimates and explicit Fourier representations.
This state-of-the-art survey features topics related to the impact of multicore, manycore, and coprocessor technologies in science and for large-scale applications in an interdisciplinary ...environment. The paperscover issues of current research in mathematical modeling, design of parallel algorithms, aspects of microprocessor architecture, parallel programming languages, hardware-aware computing, heterogeneous platforms, manycore technologies, performance tuning, and requirements for large-scale applications. The contributions presented in this volume offer a survey on the state of the art, the concepts and perspectives for future developments. They are an outcome of an inspiring conference conceived and organized by theeditors at the Karlsruhe Institute Technology (KIT) in September 2011. The twelve revised full papers presented together with two contributed papers focus on combination of new aspects of microprocessor technologies, parallel applications, numerical simulation, and software development; thus they clearly show the potential of emerging technologies in the area of multicore and manycore processors that are paving the way towards personal supercomputing and very likely towards exascale computing.
As the word “UnConventional” in the title suggests, the workshop focuses on hardware or platforms used for HPC, which were not intended for HPC in the first place. Reasons could be raw computing ...power, good performance per watt, or low cost in general. Thus, UCHPC tries to capture solutions for HPC which are unconventional today but perhaps conventional tomorrow. For example, the computing power of platforms for games recently raised rapidly. This motivated the use of GPUs for computing (GPGPU), or even building computational grids from game consoles. The recent trend of integrating GPUs on processor chips seems to be very beneficial for use of both parts for HPC. Other examples for “unconventional” hardware are embedded, low-power processors, upcoming manycore architectures, FPGAs or DSPs. Thus, interesting devices for research in unconventional HPC are not only standard server or desktop systems, but also relative cheap devices due to being mass market products, such as smartphones, netbooks, tablets and small NAS servers. For example, smartphones seem to become more performance hungry every day. Only imagination sets the limit for use of the mentioned devices for HPC. The goal of the workshop is to present latest research in how hardware and software (yet) unconventional for HPC is or can be used to reach goals such as best performance per watt. UCHPC also covers corresponding programming models, compiler techniques, and tools.
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