A Research Program on Very High Temperature Reactors

Track I: Power GenerationIncludes audio file (27 min.)Prismatic and pebble bed very high-temperature reactors (VHTRs) are very attractive both from a thermodynamic efficiency viewpoint and hydrogen-production capability. This project addresses numerous challenges associated with the fuel cycle, materials, and complex fluid dynamics and heat transfer. The objectives of the project are to: i. Conduct physical experiments for fission product transport phenomena in the overcoating and compact structural graphite and transport through TRISO coating layers; ii. Develop improved sorption measurement techniques to measure the accumulation of condensable radionuclides (“plateout”) in the VHTR primary coolant circuit and obtain representative data; iii. Develop advanced computations of charged, radioactive dust (aerosol) transport in the VHTR coolant circuit and confinement by exploring direct simulation Monte Carlo (DSMC) techniques for deposition and resuspension and conduct experiments to verify computational predictions; iv. Develop a program to measure emissivity for various VHTR component materials, both bare and oxidized, and obtain extensive data; v. Develop an experimental program to characterize gas, fission product, and particle flows in the complex geometries of pebble bed modular reactors (PBMRs) and help improve computational approaches and computer programs through experimental understandings. This project is leading to research training of about a dozen Ph D students at the participating universities. Upon graduation, these students will be able to contribute even more effectively to the future challenges in the global deployment of nuclear power generation and hydrogen technologies. We will discuss the VHTR technology and research challenges. We also describe progress on the project by the three Consortium participants

Оценка насыщения кислородом как показателя для интубации трахеи у пациентов с COVID-19: проспективное когортное исследование

   Background. Since the beginning of COVID-19 pandemic, the importance of clinical criteria for tracheal intubation in critically ill patients with respiratory failure became more noteworthy, especially in resource limitations. The objective was to evaluate the importance of hemoglobin oxygen saturation as a criterion for tracheal intubation in patients with COVID-19.   Materials and methods. This is a multi-center, prospective, observational cohort study. We included 117 patients with COVID-19 who needed respiratory support between March to June 2021. Patients were intubated by the protocol of each institution participating in the study and the anesthesiologist’s clinical judgement. Signs of respiratory failure, methods of respiratory support and patient outcome were recorded.   Results. Among 117 studied cases, 100 patients had hemoglobin oxygen saturation of 60–90 % in whom 58 were intubated. During hospitalization, 56 intubated patients and 14 non-intubated patients died (96.6 % Vs. 33.3 %).   Conclusion. Arterial blood hemoglobin oxygen saturation of 60–90 could not be the correct key to unlock the problem of intubation decision in patients with COVID-19. Therefore, hemoglobin oxygen saturation should not be solely regarded as an indication for intubation in COVID-19.    Введение. С началом пандемии COVID-19 возросла значимость клинических критериев для интубации трахеи у тяжелобольных пациентов с дыхательной недостаточностью, особенно в условиях ограниченных ресурсов.   Цель – оценить важность показателя насыщения гемоглобина кислородом как критерия для интубации трахеи у пациентов с COVID-19.   Материалы и методы. Многоцентровое проспективное обсервационное когортное исследование, включившее 117 пациентов с COVID-19, которые нуждались в респираторной поддержке в период с марта по июнь 2021 г. Пациенты были интубированы в соответствии с протоколом каждого участвовавшего в исследовании учреждения и клиническим заключением анестезиолога. Регистрировали признаки дыхательной недостаточности, методы респираторной поддержки и результаты лечения пациентов.   Результаты. Из 117 случаев у 100 пациентов насыщение гемоглобина кислородом составило 60–90 %, 58 из них были интубированы. Во время госпитализации 56 интубированных пациентов и 14 неинтубированных пациентов умерли (96,6 % против 33,3 %).   Заключение. Насыщение гемоглобина артериальной крови кислородом в пределах 60–90 % не может быть ключом к решению проблемы интубации у пациентов с COVID-19 и, следовательно, само по себе не может быть подходящим критерием для принятия решения об интубации

T1 at 1.5T and 3T compared with conventional T2* at 1.5T for cardiac siderosis

Background: Myocardial black blood (BB) T2* relaxometry at 1.5T provides robust, reproducible and calibrated non-invasive assessment of cardiac iron burden. In vitro data has shown that like T2*, novel native Modified Look-Locker Inversion recovery (MOLLI) T1 shortens with increasing tissue iron. The relative merits of T1 and T2* are largely unexplored. We compared the established 1.5T BB T2* technique against native T1 values at 1.5T and 3T in iron overload patients and in normal volunteers. Methods: A total of 73 subjects (42 male) were recruited, comprising 20 healthy volunteers (controls) and 53 patients (thalassemia major 22, sickle cell disease 9, hereditary hemochromatosis 9, other iron overload conditions 13). Single mid-ventricular short axis slices were acquired for BB T2* at 1.5T and MOLLI T1 quantification at 1.5T and 3T. Results: In healthy volunteers, median T1 was 1014 ms (full range 939–1059 ms) at 1.5T and modestly increased to 1165ms (full range 1056–1224 ms) at 3T. All patients with significant cardiac iron overload (1.5T T2* values <20 ms) had T1 values <939 ms at 1.5T, and <1056 ms at 3T. Associations between T2* and T1 were found to be moderate with y =377 · x0.282 at 1.5T (R2 = 0.717), and y =406 · x0.294 at 3T (R2 = 0.715). Measures of reproducibility of T1 appeared superior to T2*. Conclusions: T1 mapping at 1.5T and at 3T can identify individuals with significant iron loading as defined by the current gold standard T2* at 1.5T. However, there is significant scatter between results which may reflect measurement error, but it is also possible that T1 interacts with T2*, or is differentially sensitive to aspects of iron chemistry or other biology. Hurdles to clinical implementation of T1 include the lack of calibration against human myocardial iron concentration, no demonstrated relation to cardiac outcomes, and variation in absolute T1 values between scanners, which makes inter-centre comparisons difficult. The relative merits of T1 at 3T versus T2* at 3T require further consideration

Detailed Analysis of <em>ITPR1 </em>Missense Variants Guides Diagnostics and Therapeutic Design

\ua9 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Background: The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP3) receptor type 1 (IP3R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood. Objectives: We aimed to identify novel SCA29 and GLSP cases to define core phenotypes, describe the spectrum of missense variation across ITPR1, standardize the ITPR1 variant nomenclature, and investigate disease progression in relation to cerebellar atrophy. Methods: Cases were identified using next-generation sequencing through the Deciphering Developmental Disorders study, the 100,000 Genomes project, and clinical collaborations. ITPR1 alternative splicing in the human cerebellum was investigated by quantitative polymerase chain reaction. Results: We report the largest, multinational case series of 46 patients with 28 unique ITPR1 missense variants. Variants clustered in functional domains of the protein, especially in the N-terminal IP3-binding domain, the carbonic anhydrase 8 (CA8)-binding region, and the C-terminal transmembrane channel domain. Variants outside these domains were of questionable clinical significance. Standardized transcript annotation, based on our ITPR1 transcript expression data, greatly facilitated analysis. Genotype–phenotype associations were highly variable. Importantly, while cerebellar atrophy was common, cerebellar volume loss did not correlate with symptom progression. Conclusions: This dataset represents the largest cohort of patients with ITPR1 missense variants, expanding the clinical spectrum of SCA29 and GLSP. Standardized transcript annotation is essential for future reporting. Our findings will aid in diagnostic interpretation in the clinic and guide selection of variants for preclinical studies. \ua9 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Identification of myocardial diffuse fibrosis by 11 heartbeat MOLLI T1 mapping: averaging to improve precision and correlation with collagen volume fraction

Objectives: Our objectives involved identifying whether repeated averaging in basal and mid left ventricular myocardial levels improves precision and correlation with collagen volume fraction for 11 heartbeat MOLLI T1 mapping versus assessment at a single ventricular level. Materials and methods: For assessment of T1 mapping precision, a cohort of 15 healthy volunteers underwent two CMR scans on separate days using an 11 heartbeat MOLLI with a 5(3)3 beat scheme to measure native T1 and a 4(1)3(1)2 beat post-contrast scheme to measure post-contrast T1, allowing calculation of partition coefficient and ECV. To assess correlation of T1 mapping with collagen volume fraction, a separate cohort of ten aortic stenosis patients scheduled to undergo surgery underwent one CMR scan with this 11 heartbeat MOLLI scheme, followed by intraoperative tru-cut myocardial biopsy. Six models of myocardial diffuse fibrosis assessment were established with incremental inclusion of imaging by averaging of the basal and mid-myocardial left ventricular levels, and each model was assessed for precision and correlation with collagen volume fraction. Results: A model using 11 heart beat MOLLI imaging of two basal and two mid ventricular level averaged T1 maps provided improved precision (Intraclass correlation 0.93 vs 0.84) and correlation with histology (R2 = 0.83 vs 0.36) for diffuse fibrosis compared to a single mid-ventricular level alone. ECV was more precise and correlated better than native T1 mapping. Conclusion: T1 mapping sequences with repeated averaging could be considered for applications of 11 heartbeat MOLLI, especially when small changes in native T1/ECV might affect clinical management

Towards accurate and precise T1 and extracellular volume mapping in the myocardium: a guide to current pitfalls and their solutions

Mapping of the longitudinal relaxation time (T1) and extracellular volume (ECV) offers a means of identifying pathological changes in myocardial tissue, including diffuse changes that may be invisible to existing T1-weighted methods. This technique has recently shown strong clinical utility for pathologies such as Anderson- Fabry disease and amyloidosis and has generated clinical interest as a possible means of detecting small changes in diffuse fibrosis; however, scatter in T1 and ECV estimates offers challenges for detecting these changes, and bias limits comparisons between sites and vendors. There are several technical and physiological pitfalls that influence the accuracy (bias) and precision (repeatability) of T1 and ECV mapping methods. The goal of this review is to describe the most significant of these, and detail current solutions, in order to aid scientists and clinicians to maximise the utility of T1 mapping in their clinical or research setting. A detailed summary of technical and physiological factors, issues relating to contrast agents, and specific disease-related issues is provided, along with some considerations on the future directions of the field. Towards accurate and precise T1 and extracellular volume mapping in the myocardium: a guide to current pitfalls and their solutions. Available from: https://www.researchgate.net/publication/317548806_Towards_accurate_and_precise_T1_and_extracellular_volume_mapping_in_the_myocardium_a_guide_to_current_pitfalls_and_their_solutions [accessed Jun 13, 2017]

Behavioral Defects in Chaperone-Deficient Alzheimer's Disease Model Mice

Molecular chaperones protect cells from the deleterious effects of protein misfolding and aggregation. Neurotoxicity of amyloid-beta (Aβ) aggregates and their deposition in senile plaques are hallmarks of Alzheimer's disease (AD). We observed that the overall content of αB-crystallin, a small heat shock protein molecular chaperone, decreased in AD model mice in an age-dependent manner. We hypothesized that αB-crystallin protects cells against Aβ toxicity. To test this, we crossed αB-crystallin/HspB2 deficient (CRYAB-/-HSPB2-/-) mice with AD model transgenic mice expressing mutant human amyloid precursor protein. Transgenic and non-transgenic mice in chaperone-sufficient or deficient backgrounds were examined for representative behavioral paradigms for locomotion and memory network functions: (i) spatial orientation and locomotion was monitored by open field test; (ii) sequential organization and associative learning was monitored by fear conditioning; and (iii) evoked behavioral response was tested by hot plate method. Interestingly, αB-crystallin/HspB2 deficient transgenic mice were severely impaired in locomotion compared to each genetic model separately. Our results highlight a synergistic effect of combining chaperone deficiency in a transgenic mouse model for AD underscoring an important role for chaperones in protein misfolding diseases