Characterization of the thermal properties of entropy stabilized oxides and high entropy diborides

Entropy stabilized oxides and high entropy diborides are promising new materials capable of withstanding extreme environments consisting of high temperatures and pressures. In these novel materials, thermal characterization is essential for understanding and predicting performance at elevated temperatures. Moreover, these systems provide a unique opportunity to study the nature of thermal transport and phonon scattering in multicomponent, high-entropy materials. Please click on the file below for full content

Comparative treatment outcomes after bilateral extractions of maxillary second molars or first premolars in patients with class II malocclusion: a retrospective study

Background This retrospective cohort study aimed to compare treatment results between bilateral extraction of upper second molars (M2) and first premolars (P1) in terms of treatment timing, cephalometry, upper third molar alignment and relapse in the long-term. Methods Fifty-three consecutively treated Caucasian patients with a brachyfacial pattern, skeletal class I and dental class II requiring extraction in the maxilla due to crowding were retrospectively divided into group I (M2 extracted; N = 31) and II (P1 extracted; N = 22). Fixed appliances were inserted after extraction and after distalisation of the first molars in group I. Post-treatment lateral cephalograms were digitally analysed and compared between groups. Six to seven years later relapse and success of upper third molar alignment were clinically evaluated as well as orthodontic treatment duration, pre-treatment age and gender recorded. Results After debonding patients with second molar extraction showed significantly smaller values for the Wits-appraisal, but higher values for index and facial axis. Extracting first premolars caused significantly more retroinclination/−position of anterior teeth and an increased profile concavity, more relapse and less successful alignment of upper third molars. Orthodontic treatment duration, pre-treatment age and gender were not significantly different between groups. Conclusions Bilateral extraction of upper first premolars or second molars may solve dental crowding in skeletal class I dental class II patients with a brachyfacial growth pattern. Upper second molar extraction seems to affect maxillary third molar alignment, long-term stability and dental and soft-tissue cephalometric parameters positively, but no intervention proved to be clearly superior

Measurements and simulations of the phonon thermal conductivity of entropy stabilized alloys

The phonon thermal conductivity of solids is intimately related to any changes in atomic scale periodicity. As a classic example, the phonon thermal conductivity of alloys can be greatly reduces as compared to that of the corresponding non-alloy parent materials. However, the improved mechanical properties and environmental stability of alloyed materials makes these multi-atom solids ideal for a wide variety of applications. In this sense, entropy stabilized oxides and high entropy diborides are promising new materials that have potential to withstand extreme environments consisting of high temperatures and pressures. In these novel materials, thermal characterization is essential for understanding and predicting performance at elevated temperatures, as the presence of multi atomic species (5+ different atoms) in these solid solutions could lead to drastically modified phonon scattering rates and thermal conductivities. In this talk, we present recent measurements and molecular dynamics simulations on multiple atom alloys, including entropy stabilized oxides and high entropy diborides. We use time-domain thermoreflectance (TDTR), and optical pump-probe technique, to measure the thermal conductivity of these various systems. We also demonstrate the ability to extend TDTR measurements to temperatures above 1000 deg. C. The TDTR measurements show drastic reductions in the thermal conductivity of these crystalline solid solution materials, approaching values of the amorphous phases. These reductions in thermal conductivity can not be explained by phonon-mass scattering alone. Thus, to investigate the nature of the reduction in thermal conductivity of these multi-atom solid solutions, we turn to classical molecular dynamics simulations. In agreement with the Klemens’ perturbation theory, the thermal conductivity reduction due to mass scattering alone is found to reach a critical point, whereby adding more impurity atoms in the solid solution does not reduce the thermal conductivity. A further decrease in thermal conductivity requires a change in local strain-field, which together with mass defect scattering can lead to ultralow thermal conductivities in solid solutions, which surpasses the theoretical minimum limit of the corresponding amorphous phases. These simulations qualitatively agree well with our experimental measurements, and add insight into the nature of phonon scattering in entropy stabilized materials. This work is supported by the U.S. Office of Naval Research MURI program (grant No. N00014-15-1-2863)

Phonon scattering mechanisms contributing to the low thermal conductivities of entropy stabilized oxides and high entropy carbides

The phonon thermal conductivity of solids is intimately related to any changes in atomic scale periodicity. As a classic example, the phonon thermal conductivity of alloys can be greatly reduced as compared to that of the corresponding non-alloy parent materials. However, the improved mechanical properties and environmental stability of alloyed materials makes these multi-atom solids ideal for a wide variety of applications. In this sense, entropy stabilized oxides and high entropy carbides are promising new materials that have potential to withstand extreme environments consisting of high temperatures and pressures. In these novel materials, thermal characterization is essential for understanding and predicting performance at elevated temperatures, as the presence of multi atomic species (5+ different atoms) in these solid solutions could lead to drastically modified phonon scattering rates and thermal conductivities. In this talk, we present recent measurements and molecular dynamics simulations on multiple atom alloys, including entropy stabilized oxides and high entropy diborides. We use time-domain thermoreflectance (TDTR), and optical pump-probe technique, to measure the thermal conductivity of these various systems. We also demonstrate the ability to extend TDTR measurements to temperatures above 1000 deg. C. The TDTR measurements show drastic reductions in the thermal conductivity of these crystalline solid solution materials, approaching values of the amorphous phases. These reductions in thermal conductivity can not be explained by phonon-mass scattering alone. Thus, to investigate the nature of the reduction in thermal conductivity of these multi-atom solid solutions, we turn to classical molecular dynamics simulations. In agreement with the Klemens’ perturbation theory, the thermal conductivity reduction due to mass scattering alone is found to reach a critical point, whereby adding more impurity atoms in the solid solution does not reduce the thermal conductivity. A further decrease in thermal conductivity requires a change in local strain-field, which together with mass defect scattering can lead to ultralow thermal conductivities in solid solutions, which surpasses the theoretical minimum limit of the corresponding amorphous phases. These simulations qualitatively agree well with our experimental measurements, and add insight into the nature of phonon scattering in entropy stabilized materials. This work is supported by the U.S. Office of Naval Research MURI program (grant No. N00014-15-1-2863

Identification of glucocorticoid-related molecular signature by whole blood methylome analysis

Objective Cushing's syndrome represents a state of excessive glucocorticoids related to glucocorticoid treatments or to endogenous hypercortisolism. Cushing's syndrome is associated with high morbidity, with significant inter-individual variability. Likewise, adrenal insufficiency is a life-threatening condition of cortisol deprivation. Currently, hormone assays contribute to identify Cushing's syndrome or adrenal insufficiency. However, no biomarker directly quantifies the biological glucocorticoid action. The aim of this study was to identify such markers. Design We evaluated whole blood DNA methylome in 94 samples obtained from patients with different glucocorticoid states (Cushing's syndrome, eucortisolism, adrenal insufficiency). We used an independent cohort of 91 samples for validation. Methods Leukocyte DNA was obtained from whole blood samples. Methylome was determined using the Illumina methylation chip array (~850 000 CpG sites). Both unsupervised (principal component analysis) and supervised (Limma) methods were used to explore methylome profiles. A Lasso-penalized regression was used to select optimal discriminating features. Results Whole blood methylation profile was able to discriminate samples by their glucocorticoid status: glucocorticoid excess was associated with DNA hypomethylation, recovering within months after Cushing's syndrome correction. In Cushing's syndrome, an enrichment in hypomethylated CpG sites was observed in the region of FKBP5 gene locus. A methylation predictor of glucocorticoid excess was built on a training cohort and validated on two independent cohorts. Potential CpG sites associated with the risk for specific complications, such as glucocorticoid-related hypertension or osteoporosis, were identified, needing now to be confirmed on independent cohorts. Conclusions Whole blood DNA methylome is dynamically impacted by glucocorticoids. This biomarker could contribute to better assessment of glucocorticoid action beyond hormone assays

Whole blood methylome-derived features to discriminate endocrine hypertension

Background: Arterial hypertension represents a worldwide health burden and a major risk factor for cardiovascular morbidity and mortality. Hypertension can be primary (primary hypertension, PHT), or secondary to endocrine disorders (endocrine hypertension, EHT), such as Cushing's syndrome (CS), primary aldosteronism (PA), and pheochromocytoma/paraganglioma (PPGL). Diagnosis of EHT is currently based on hormone assays. Efficient detection remains challenging, but is crucial to properly orientate patients for diagnostic confirmation and specific treatment. More accurate biomarkers would help in the diagnostic pathway. We hypothesized that each type of endocrine hypertension could be associated with a specific blood DNA methylation signature, which could be used for disease discrimination. To identify such markers, we aimed at exploring the methylome profiles in a cohort of 255 patients with hypertension, either PHT (n = 42) or EHT (n = 213), and at identifying specific discriminating signatures using machine learning approaches. Results: Unsupervised classification of samples showed discrimination of PHT from EHT. CS patients clustered separately from all other patients, whereas PA and PPGL showed an overall overlap. Global methylation was decreased in the CS group compared to PHT. Supervised comparison with PHT identified differentially methylated CpG sites for each type of endocrine hypertension, showing a diffuse genomic location. Among the most differentially methylated genes, FKBP5 was identified in the CS group. Using four different machine learning methods—Lasso (Least Absolute Shrinkage and Selection Operator), Logistic Regression, Random Forest, and Support Vector Machine—predictive models for each type of endocrine hypertension were built on training cohorts (80% of samples for each hypertension type) and estimated on validation cohorts (20% of samples for each hypertension type). Balanced accuracies ranged from 0.55 to 0.74 for predicting EHT, 0.85 to 0.95 for predicting CS, 0.66 to 0.88 for predicting PA, and 0.70 to 0.83 for predicting PPGL. Conclusions: The blood DNA methylome can discriminate endocrine hypertension, with methylation signatures for each type of endocrine disorder

SARS-CoV-2-Abwassersurveillance in Deutschland im Rahmen des Projekts AMELAG

Ausgelöst durch die COVID-19-Pandemie wird die Abwassersurveillance inzwischen weltweit im Rahmen des präventiven Gesundheitsschutzes genutzt. Im Vergleich zu individuellen Testungen kann durch die Abwasserbeprobung die Entwicklung des Infektionsgeschehens unabhängig von der aktuellen diagnostischen Teststrategie bzw. der Inanspruchnahme medizinischer Dienstleistungen durch die Bevölkerung verfolgt werden. Seit Anfang 2020 wird die SARS-CoV-2-Abwasser-surveillance in Deutschland in verschiedenen Projekten aufgebaut und umgesetzt. Das Projekt AMELAG („Abwassermonitoring für die epidemiologische Lagebewertung“) unter gemeinsamer Leitung von Robert Koch-Institut und Umweltbundesamt verfolgt das Ziel, die Viruslast und die zirkulierenden SARS-CoV-2-Varianten im Abwasser zu überwachen, Forschungsfragen zu bearbeiten, Verfahren zur Detektion weiterer Erreger zu etablieren und die gesamte Kette von Probenahme in der Kläranlage bis zur Datenbewertung zu erweitern, zu harmonisieren und zu optimieren

Common coding variant in SERPINA1 increases the risk for large artery stroke

Large artery atherosclerotic stroke (LAS) shows substantial heritability not explained by previous genome-wide association studies. Here, we explore the role of coding variation in LAS by analyzing variants on the HumanExome BeadChip in a total of 3,127 cases and 9,778 controls from Europe, Australia, and South Asia. We report on a nonsynonymous single-nucleotide variant in serpin family A member 1 (SERPINA1) encoding alpha-1 antitrypsin [AAT; p.V213A; P = 5.99E-9, odds ratio (OR) = 1.22] and confirm histone deacetylase 9 (HDAC9) as a major risk gene for LAS with an association in the 3?-UTR (rs2023938; P = 7.76E-7, OR = 1.28). Using quantitative microscale thermophoresis, we show that M1 (A213) exhibits an almost twofold lower dissociation constant with its primary target human neutrophil elastase (NE) in lipoprotein-containing plasma, but not in lipid-free plasma. Hydrogen/deuterium exchange combined with mass spectrometry further revealed a significant difference in the global flexibility of the two variants. The observed stronger interaction with lipoproteins in plasma and reduced global flexibility of the Val-213 variant most likely improve its local availability and reduce the extent of proteolytic inactivation by other proteases in atherosclerotic plaques. Our results indicate that the interplay between AAT, NE, and lipoprotein particles is modulated by the gate region around position 213 in AAT, far away from the unaltered reactive center loop (357-360). Collectively, our findings point to a functionally relevant balance between lipoproteins, proteases, and AAT in atherosclerosis

Oral abstracts 1: SpondyloarthropathiesO1. Detecting axial spondyloarthritis amongst primary care back pain referrals

Background: Inflammatory back pain (IBP) is an early feature of ankylosing spondylitis (AS) and its detection offers the prospect of early diagnosis of AS. However, since back pain is very common but only a very small minority of back pain sufferers have ASpA or AS, screening of back pain sufferers for AS is problematic. In early disease radiographs are often normal so that fulfilment of diagnostic criteria for AS is impossible though a diagnosis of axial SpA can be made if MRI evidence of sacroiliitis is present. This pilot study was designed to indicate whether a cost-effective pick up rate for ASpA/early AS could be achieved by identifying adults with IBP stratified on the basis of age. Methods: Patients aged between 18 and 45 years who were referred to a hospital physiotherapy service with back pain of more than 3 months duration were assessed for IBP. All were asked to complete a questionnaire based on the Berlin IBP criteria. Those who fulfilled IBP criteria were also asked to complete a second short questionnaire enquiring about SpA comorbidities, to have a blood test for HLA-B27 and CRP level and to undergo an MRI scan of the sacroiliac joints. This was a limited scan, using STIR, diffusion-weighted, T1 and T2 sequences of the sacroiliac joints to minimize time in the scanner and cost. The study was funded by a research grant from Abbott Laboratories Ltd. Results: 50 sequential patients agreed to participate in the study and completed the IBP questionnaire. Of these 27 (54%) fulfilled criteria for IBP. Of these, 2 patients reported a history of an SpA comorbidity - 1 psoriasis; 1 ulcerative colitis - and 3 reported a family history of an SpA comorbidity - 2 psoriasis; 1 Crohn's disease. 4 were HLA-B27 positive, though results were not available for 7. Two patients had marginally raised CRP levels (6, 10 -NR ≤ 5). 19 agreed to undergo MRI scanning of the sacroiliac joints and lumbar spine; 4 scans were abnormal, showing evidence of bilateral sacroiliitis on STIR sequences. In all cases the changes met ASAS criteria but were limited. Of these 4 patients 3 were HLA-B27 positive but none gave a personal or family history of an SpA-associated comorbidity and all had normal CRP levels. Conclusions: This was a pilot study yielding only limited conclusions. However, it is clear that: Screening of patients referred for physiotherapy for IBP is straightforward, inexpensive and quick. It appears that IBP is more prevalent in young adults than overall population data suggest so that targeting this population may be efficient. IBP questionnaires could be administered routinely during a physiotherapy assessment. HLA-B27 testing in this group of patients with IBP is a suitable screening tool. The sacroiliac joint changes identified were mild and their prognostic significance is not yet clear so that the value of early screening needs further evaluation. Disclosure statement: C.H. received research funding for this study from Abbott. A.K. received research funding for this study, and speaker and consultancy fees, from Abbott. All other authors have declared no conflicts of interes