Deep learning based surrogate modeling for thermal plume prediction of groundwater heat pumps

The ability for groundwater heat pumps to meet space heating and cooling demands without relying on fossil fuels, has prompted their mass roll out in dense urban environments. In regions with high subsurface groundwater flow rates, the thermal plume generated from a heat pump's injection well can propagate downstream, affecting surrounding users and reducing their heat pump efficiency. To reduce the probability of interference, regulators often rely on simple analytical models or high fidelity groundwater simulations to determine the impact that a heat pump has on the subsurface aquifer and surrounding heat pumps. These are either too inaccurate or too computationally expensive for everyday use. In this work, a surrogate model was developed to provide a quick, high accuracy prediction tool of the thermal plume generated by a heat pump within heterogeneous subsurface aquifers. Three variations of a convolutional neural network were developed that accepts the known groundwater Darcy velocities as discrete two-dimensional inputs and predicts the temperature within the subsurface aquifer around the heat pump. A data set consisting of 800 numerical simulation samples, generated from random permeability fields and pressure boundary conditions, was used to provide pseudo-randomized Darcy velocity fields as input fields and the temperature field solution for training the network. The subsurface temperature field output from the network provides a more realistic temperature field that follows the Darcy velocity streamlines, while being orders of magnitude faster than conventional high fidelity solversComment: 24 pages, 11 figure

Comparative Study on High Strain Rate Fracture Modelling Using the Application of Explosively Driven Cylinder Rings

The effect of different constitutive modelling choices is crucial under a high strain rate as encountered in ballistic applications. Natural fragmentation of explosively driven cylinder rings is chosen as a simplified example to describe the ability of numerical simulations to describe fractures. The main research interests are the importance of (i) material imperfections, (ii) the accuracy of fracture models vs. damage models, (iii) the plasticity algorithm (stress update), (iv) the introduction of a triaxiality cutoff criterion to the damage models, and (v) different constitutive models (plasticity and damage). Due to the complexity of the propagation and coalescense of multiple cracks in classical methods, smoothed-particle hydrodynamics (SPH) is used as a tailor-made method to discretise the model. An elasto-plasticity model, a damage model and an equation of state describe the material behaviour. The required material parameters are determined based on stress–strain curves from quasi-static and dynamic tests. The Johnson–Cook model, with and without a modification of the strain rate term, and the Rusinek–Klepaczko model are used to describe plasticity. These plasticity models are combined either with the Johnson–Cook, the Lemaitre, or the Dolinski–Rittel damage model and the Mie–Grüneisen equation of state. The numerical results show that (i) a random distribution of initial damage increases irregularity of cracks, and gives more realistic fragment shapes, (ii) a coupling of plasticity model and fracture criterion has only a small effect on the fracture behaviour, (iii) using an iterative plasticity solver has a positive effect on the fracture behaviour, although this effect is marginal, (iv) adding a triaxiality cutoff criterion to the damage models improves the predicted fragment masses in the numerical simulations significantly, and (v) good accordance between experiments and numerical simulations are found for the Dolinski–Rittel and Lemaitre damage model with both plasticity models.Peer reviewe

CLAIRE -- Parallelized Diffeomorphic Image Registration for Large-Scale Biomedical Imaging Applications

We study the performance of CLAIRE -- a diffeomorphic multi-node, multi-GPU image-registration algorithm, and software -- in large-scale biomedical imaging applications with billions of voxels. At such resolutions, most existing software packages for diffeomorphic image registration are prohibitively expensive. As a result, practitioners first significantly downsample the original images and then register them using existing tools. Our main contribution is an extensive analysis of the impact of downsampling on registration performance. We study this impact by comparing full-resolution registrations obtained with CLAIRE to lower-resolution registrations for synthetic and real-world imaging datasets. Our results suggest that registration at full resolution can yield a superior registration quality -- but not always. For example, downsampling a synthetic image from $1024^3$ to $256^3$ decreases the Dice coefficient from 92% to 79%. However, the differences are less pronounced for noisy or low-contrast high-resolution images. CLAIRE allows us not only to register images of clinically relevant size in a few seconds but also to register images at unprecedented resolution in a reasonable time. The highest resolution considered is CLARITY images of size $2816\times3016\times1162$. To the best of our knowledge, this is the first study on image registration quality at such resolutions.Comment: 32 pages, 9 tables, 8 figure

Evaluation of two family-based intervention programs for children affected by rare disease and their families – research network (CARE-FAM-NET): study protocol for a rater-blinded, randomized, controlled, multicenter trial in a 2x2 factorial design

Background: Families of children with rare diseases (i.e., not more than 5 out of 10,000 people are affected) are often highly burdened with fears, insecurities and concerns regarding the affected child and its siblings. Although families caring for children with rare diseases are known to be at risk for mental disorders, the evaluation of special programs under high methodological standards has not been conducted so far. Moreover, the implementation of interventions for this group into regular care has not yet been accomplished in Germany. The efficacy and cost-effectiveness of a family-based intervention will be assessed. Methods/design: The study is a 2x2 factorial randomized controlled multicenter trial conducted at 17 study centers throughout Germany. Participants are families with children and adolescents affected by a rare disease aged 0 to 21 years. Families in the face-to-face intervention CARE-FAM, online intervention WEP-CARE or the combination of both will be treated over a period of roughly 6 months. Topics discussed in the interventions include coping, family relations, and social support. Families in the control condition will receive treatment as usual. The primary efficacy outcome is parental mental health, measured by the Structured Clinical Interview for DSM-IV (SCID-I) by blinded external raters. Further outcomes will be assessed from the parents’ as well as the children’s perspective. Participants are investigated at baseline, 6, 12 and 18 months after randomization. In addition to the assessment of various psychosocial outcomes, a comprehensive health-economic evaluation will be performed. Discussion: This paper describes the implementation and evaluation of two family-based intervention programs for Children Affected by Rare Disease and their Family’s Network (CARE-FAM-NET) in German standard care. A methodologically challenging study design is used to reflect the complexity of the actual medical care situation. This trial could be an important contribution to the improvement of care for this highly burdened group. Trial registration: German Clinical Trials Register: DRKS00015859 (registered 18 December 2018) and ClinicalTrials.gov: NCT04339465 (registered 8 April 2020). Protocol Version: 15 August 2020 (Version 6.1). Trial status: Recruitment started on 1 January 2019 and will be completed on 31 March 2021. © 2020, The Author(s)

Prospective evaluation of NGS-based sequencing in epilepsy patients: results of seven NASGE-associated diagnostic laboratories

BackgroundEpilepsy is one of the most common and disabling neurological disorders. It is highly prevalent in children with neurodevelopmental delay and syndromic diseases. However, epilepsy can also be the only disease-determining symptom. The exact molecular diagnosis is essential to determine prognosis, comorbidity, and probability of recurrence, and to inform therapeutic decisions.Methods and materialsHere, we describe a prospective cohort study of patients with epilepsy evaluated in seven diagnostic outpatient centers in Germany. Over a period of 2 months, 07/2022 through 08/2022, 304 patients (317 returned result) with seizure-related human phenotype ontology (HPO) were analyzed. Evaluated data included molecular results, phenotype (syndromic and non-syndromic), and sequencing methods.ResultsSingle exome sequencing (SE) was applied in half of all patients, followed by panel (P) testing (36%) and trio exome sequencing (TE) (14%). Overall, a pathogenic variant (PV) (ACMG cl. 4/5) was identified in 22%; furthermore, a significant number of patients (12%) carried a reported clinically meaningful variant of unknown significance (VUS). The average diagnostic yield in patients ≤ 12 y was higher compared to patients >12 y cf. Figure 2B vs. Figure 3B. This effect was more pronounced in cases, where TE was applied in patients ≤ 12 vs. >12 y [PV (PV + VUS): patients ≤ 12 y: 35% (47%), patients > 12 y: 20% (40%)]. The highest diagnostic yield was achieved by TE in syndromic patients within the age group ≤ 12 y (ACMG classes 4/5 40%). In addition, TE vs. SE had a tendency to result in less VUS in patients ≤ 12 y [SE: 19% (22/117) VUS; TE: 17% (6/36) VUS] but not in patients >12 y [SE: 19% (8/42) VUS; TE: 20% (2/10) VUS]. Finally, diagnostic findings in patients with syndromic vs. non-syndromic symptoms revealed a significant overlap of frequent causes of monogenic epilepsies, including SCN1A, CACNA1A, and SETD1B, confirming the heterogeneity of the associated conditions.ConclusionIn patients with seizures—regardless of the detailed phenotype—a monogenic cause can be frequently identified, often implying a possible change in therapeutic action (36.7% (37/109) of PV/VUS variants); this justifies early and broad application of genetic testing. Our data suggest that the diagnostic yield is highest in exome or trio-exome-based testing, resulting in a molecular diagnosis within 3 weeks, with profound implications for therapeutic strategies and for counseling families and patients regarding prognosis and recurrence risk

Exome-wide association study to identify rare variants influencing COVID-19 outcomes : Results from the Host Genetics Initiative

Publisher Copyright: Copyright: © 2022 Butler-Laporte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.Peer reviewe

A roupa nova do presidente: a politização da imagem pública de Jânio Quadros (1947-1961)

Jânio Quadros public image is often considered deprived of any political meaning either by historians or by collective memory. In most cases he is treated as a demagogue who promoted himself only through his personalism, which could be seen in his public appearances unkempt and with open-necked shirts. Such perspective is deeply related to the way his opponents and enemies represented him in the political debates, and its core has been successful in penetrating the historiography. However in this text I intend to suggest that Jânio's images conveyed an array of political senses during the 1950s and early 1960s, since the beginning of his career till when he disputed presidential elections and ruled Brazil as president. Through his gestures and clothes, among which his Indian slacks deserve more attention, he tried to express his project related to the Christian Democracy and the Independent Foreign Policy. To deal with such hypothesis, the main sources will be the magazines O Cruzeiro and Manchete and others photos and drawings that were considerably widespread at that time.A imagem pública de Jânio Quadros é frequentemente considerada como desprovida de quaisquer significados políticos, seja por historiadores ou pela memória coletiva. Na maioria dos casos, ele é tratado como um demagogo que se promovia apenas através de seu personalismo, exibindo-se em suas aparições públicas despenteado e com camisas abertas no colarinho. Tal perspectiva está profundamente relacionada com a forma pela qual seus oponentes e inimigos o representavam nos debates políticos, e em seu cerne foi bem-sucedida, tendo penetrado na historiografia. Neste texto, porém, pretendo sugerir que, perpassando a década de 1950 e o início da de 1960, desde o início de sua carreira até o momento em que disputou eleições presidenciais e foi o presidente do Brasil, as imagens de Jânio veiculavam um amplo leque de sentidos políticos. Por meio de gestos e roupas, destacando-se aí seus slacks indianos, ele procurou expressar seus projetos relacionados à Democracia Cristã e à Política Externa Independente. Para lidar com essa hipótese, as principais fontes fotográficas e textuais elencadas são as revistas O Cruzeiro e Manchete da época, e outras fotos e ilustrações que então foram bastante difundidas