Selected papers from OECD-NEA PSBT benchmark

Historically, the prediction of safety margins has been based on system level thermal-hydraulic calculations employing suitable empirical formulations for assembly specific geometries and fuel-element grid spacers. These works have assessed response, margins, and consequences for the system based on one-dimensional two-fluid or drift-flux type thermalhydraulics formulations with fuel-vendor specific hydraulic losses and heat transfer characteristics for various fuel assemblies, including the so-called hot channel. Analysis of the hot channel gives important information on flow rates, fuel element centerline temperature, fuel sheath temperature, and margin to the departure from nucleate boiling. Given the reliance of the above approaches on empirical formulations obtained from complex and often difficult experiments, there is significant interest in obtaining reliable and accurate results from computation tools which employ more fundamental empirical relationships which can be obtained from subsets of the domain or from other scaled experiments

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian consensus conference on pain in neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

High-resolution experiments for mixing in large enclosures

To support further model development and validation for mixing in large enclosures, the MiGaDome facility that is 1/12th scaled from the Modular High-Temperature Gas Reactor (MHTGR) upper plenum has recently been built at the University of Michigan. In this paper, 2D PIV measurements have been conducted on two jets discharging into the MiGaDome facility. Two twin-jet cases of Re=4097 and Re=6021, and an asymmetrical case (Re=6021 v.s. 4097) have been investigated. Intense turbulent mixing with spanwise vortices of various sizes is observed in the instantaneous vector field for all cases. A power spectrum density analysis with a 7.5 Hz cutoff frequency has shown low-frequency fluctuations of St=0.0144 and St=0.0120 in the middle of the two jets for the two uniform injection cases. Besides, the time-averaged flow field shows that a down-wash fountain flow has formed due to wall jet impingement for the two cases, while a clockwise recirculation is created for the asymmetrical case. High-resolution 2D velocity and turbulent statistics fields have been obtained from the time-averaged measurements. In addition, the integral length scales are also calculated based on the two-point spatial cross-correlation.ISSN:0029-5493ISSN:1872-759

Simulation and experiments on the feasibility of using gamma tomography for void fraction measurements in nuclear fuel bundle mock-ups

The High-Resolution Gamma Tomography System (HRGTS) facility is under development at the University of Michigan. This system is planned generally for application to two-phase flow loops representing nuclear fuel bundles. These measurements should provide insight into fluid dynamics phenomena and high resolution data for validation of computational fluid dynamics (CFD) codes. The HRGTS is planned to be deployed in the Michigan Advanced Rod Bundle fLow Experiment (MARBLE). an adiabatic test loop consisting of an 8x8 square lattice arrangement. Simulations modeling MARBLE were performed to study how the counting statistics of the imaging process propagate into void fraction uncertainty. The simulation results showed that an accuracy of around 1% is expected with imaging times of 1 min. Computed tomography measurements were performed on partial mockups of the bundle geometry, which confirmed that the technique can be used to obtain accurate subchannel void fraction data in complicated and challenging measurement scenarios.ISSN:0306-454

Analysis of Void Fraction Distribution and Departure from Nucleate Boiling in Single Subchannel and Bundle Geometries Using Subchannel, System, and Computational Fluid Dynamics Codes

In order to assess the accuracy and validity of subchannel, system, and computational fluid dynamics codes, the Paul Scherrer Institut has participated in the OECD/NRC PSBT benchmark with the thermal-hydraulic system code TRACE5.0 developed by US NRC, the subchannel code FLICA4 developed by CEA, and the computational fluid dynamic code STAR-CD developed by CD-adapco. The PSBT benchmark consists of a series of void distribution exercises and departure from nucleate boiling exercises. The results reveal that the prediction by the subchannel code FLICA4 agrees with the experimental data reasonably well in both steady-state and transient conditions. The analyses of single-subchannel experiments by means of the computational fluid dynamic code STAR-CD with the CD-adapco boiling model indicate that the prediction of the void fraction has no significant discrepancy from the experiments. The analyses with TRACE point out the necessity to perform additional assessment of the subcooled boiling model and bulk condensation model of TRACE