Search

In the Netherlands, drug regulatory science is a vibrant national and internationally oriented community. In this review, we present the factors that have contributed to this successful collaboration between relevant stakeholders and that led to a surge of activities around how regulatory science became embedded in the ecosystem of medicines research, clinical pharmacology, policymaking and regulation. We distinguished three pivotal episodes: (i) TI Pharma Escher-project, (ii) Dutch Medicines Evaluation Board as catalyst of the big jump, and (iii) Regulatory Science Network Netherlands and multistakeholder engagement. The research agenda has been influenced by the dynamic evolution of legal frameworks in Europe, such as the EU orphan medicines legislation of 2001 and the EU pharmacovigilance legislation of 2012. All these developments have inspired and have raised pertinent regulatory sciences questions. Furthermore, clinical pharmacology as a discipline has been very influential in shaping regulatory science, contributing to discussions on the level of clinical evidence that is necessary to justify marketing approval of a new medicine. With a growing interest of multiple parties such as academics, European Medicines Agency, national agencies, patient organizations and EFPIA, connecting regulatory science activities is key.

As we learn more about the multi-scale interstellar medium (ISM) of our Galaxy, we develop a greater understanding for the complex relationships between the large-scale diffuse gas and dust in Giant Molecular Clouds (GMCs), how it moves, how it is affected by the nearby massive stars, and which portions of those GMCs eventually collapse into star forming regions. The complex interactions of those gas, dust and stellar populations form what has come to be known as the ecology of our Galaxy. Because we are deeply embedded in the plane of our Galaxy, it takes up a significant fraction of the sky, with complex dust lanes scattered throughout the optically recognizable bands of the Milky Way. These bands become bright at (sub-)millimetre wavelengths, where we can study dust thermal emission and the chemical and kinematic signatures of the gas. To properly study such large-scale environments, requires deep, large area surveys that are not possible with current facilities. Moreover, where stars form, so too do planetary systems, growing from the dust and gas in circumstellar discs, to planets and planetesimal belts. Understanding the evolution of these belts requires deep imaging capable of studying belts around young stellar objects to Kuiper belt analogues around the nearest stars. Here we present a plan for observing the Galactic Plane and circumstellar environments to quantify the physical structure, the magnetic fields, the dynamics, chemistry, star formation, and planetary system evolution of the galaxy in which we live with AtLAST; a concept for a new, 50m single-dish sub-mm telescope with a large field of view which is the only type of facility that will allow us to observe our Galaxy deeply and widely enough to make a leap forward in our understanding of our local ecology.

Bipolar disorder (BD) is a heritable disorder characterized by shifts in mood that manifest in manic or depressive episodes. Clinical studies have identified abnormalities of the circadian system in BD patients as a hallmark of underlying pathophysiology. Fibroblasts are a well-established in vitro model for measuring circadian patterns. We set out to examine the underlying genetic architecture of circadian rhythm in fibroblasts, with the goal to assess its contribution to the polygenic nature of BD disease risk. We collected, from primary cell lines of 6 healthy individuals, temporal genomic features over a 48 h period from transcriptomic data (RNA-seq) and open chromatin data (ATAC-seq). The RNA-seq data showed that only a limited number of genes, primarily the known core clock genes such as ARNTL, CRY1, PER3, NR1D2 and TEF display circadian patterns of expression consistently across cell cultures. The ATAC-seq data identified that distinct transcription factor families, like those with the basic helix-loop-helix motif, were associated with regions that were increasing in accessibility over time. Whereas known glucocorticoid receptor target motifs were identified in those regions that were decreasing in accessibility. Further evaluation of these regions using stratified linkage disequilibrium score regression analysis failed to identify a significant presence of them in the known genetic architecture of BD, and other psychiatric disorders or neurobehavioral traits in which the circadian rhythm is affected. In this study, we characterize the biological pathways that are activated in this in vitro circadian model, evaluating the relevance of these processes in the context of the genetic architecture of BD and other disorders, highlighting its limitations and future applications for circadian genomic studies.

Genome-wide association studies (GWASs) have uncovered susceptibility loci associated with psychiatric disorders such as bipolar disorder (BP) and schizophrenia (SCZ). However, most of these loci are in non-coding regions of the genome, and the causal mechanisms of the link between genetic variation and disease risk is unknown. Expression quantitative trait locus (eQTL) analysis of bulk tissue is a common approach used for deciphering underlying mechanisms, although this can obscure cell-type-specific signals and thus mask trait-relevant mechanisms. Although single-cell sequencing can be prohibitively expensive in large cohorts, computationally inferred cell-type proportions and cell-type gene expression estimates have the potential to overcome these problems and advance mechanistic studies. Using bulk RNA-seq from 1,730 samples derived from whole blood in a cohort ascertained from individuals with BP and SCZ, this study estimated cell-type proportions and their relation with disease status and medication. For each cell type, we found between 2,875 and 4,629 eGenes (genes with an associated eQTL), including 1,211 that are not found on the basis of bulk expression alone. We performed a colocalization test between cell-type eQTLs and various traits and identified hundreds of associations that occur between cell-type eQTLs and GWASs but that are not detected in bulk eQTLs. Finally, we investigated the effects of lithium use on the regulation of cell-type expression loci and found examples of genes that are differentially regulated according to lithium use. Our study suggests that applying computational methods to large bulk RNA-seq datasets of non-brain tissue can identify disease-relevant, cell-type-specific biology of psychiatric disorders and psychiatric medication.

In this cohort profile article we describe the lifetime major depressive disorder (MDD) database that has been established as part of the BIObanks Netherlands Internet Collaboration (BIONIC). Across the Netherlands we collected data on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lifetime MDD diagnosis in 132,850 Dutch individuals. Currently, N = 66,684 of these also have genomewide single nucleotide polymorphism (SNP) data. We initiated this project because the complex genetic basis of MDD requires large population-wide studies with uniform in-depth phenotyping. For standardized phenotyping we developed the LIDAS (LIfetime Depression Assessment Survey), which then was used to measure MDD in 11 Dutch cohorts. Data from these cohorts were combined with diagnostic interview depression data from 5 clinical cohorts to create a dataset of N = 29,650 lifetime MDD cases (22%) meeting DSM-5 criteria and 94,300 screened controls. In addition, genomewide genotype data from the cohorts were assembled into a genomewide association study (GWAS) dataset of N = 66,684 Dutch individuals (25.3% cases). Phenotype data include DSM-5-based MDD diagnoses, sociodemographic variables, information on lifestyle and BMI, characteristics of depressive symptoms and episodes, and psychiatric diagnosis and treatment history. We describe the establishment and harmonization of the BIONIC phenotype and GWAS datasets and provide an overview of the available information and sample characteristics. Our next step is the GWAS of lifetime MDD in the Netherlands, with future plans including fine-grained genetic analyses of depression characteristics, international collaborations and multi-omics studies.

The phase behavior is investigated for systems composed of a large number of macromolecular components N, with N ≥ 2. Liquid-liquid phase separation is modeled using a virial expansion up to the second order of the concentrations of the components. Formal analytical expressions for the spinodal manifolds in N dimensions are derived, which simplify their calculation (by transforming the original problem into inequalities that can be evaluated numerically using linear programming techniques). In addition, a new expression is obtained to calculate the critical manifold and composition of the coexisting phases. The present analytical procedure complements previous attempts to handle spinodal decomposition for many components using a statistical approach based on random matrix theory. The results are relevant for predicting the effects of polydispersity on phase behavior in fields like polymer or food science and liquid-liquid phase separation in the cytosol of living cells.

Aims: The interleukin-1 receptor accessory protein (IL1RAP) is a co-receptor required for signalling through the IL-1, IL-33, and IL-36 receptors. Using a novel anti-IL1RAP-blocking antibody, we investigated the role of IL1RAP in atherosclerosis. Methods and results: Single-cell RNA sequencing data from human atherosclerotic plaques revealed the expression of IL1RAP and several IL1RAP-related cytokines and receptors, including IL1B and IL33. Histological analysis showed the presence of IL1RAP in both the plaque and adventitia, and flow cytometry of murine atherosclerotic aortas revealed IL1RAP expression on plaque leucocytes, including neutrophils and macrophages. High-cholesterol diet fed apolipoprotein E-deficient (Apoe-/-) mice were treated with a novel non-depleting IL1RAP-blocking antibody or isotype control for the last 6 weeks of diet. IL1RAP blockade in mice resulted in a 20% reduction in subvalvular plaque size and limited the accumulation of neutrophils and monocytes/macrophages in plaques and of T cells in adventitia, compared with control mice. Indicative of reduced plaque inflammation, the expression of several genes related to leucocyte recruitment, including Cxcl1 and Cxcl2, was reduced in brachiocephalic arteries of anti-IL1RAP-treated mice, and the expression of these chemokines in human plaques was mainly restricted to CD68+ myeloid cells. Furthermore, in vitro studies demonstrated that IL-1, IL-33, and IL-36 induced CXCL1 release from both macrophages and fibroblasts, which could be mitigated by IL1RAP blockade. Conclusion: Limiting IL1RAP-dependent cytokine signalling pathways in atherosclerotic mice reduces plaque burden and plaque inflammation, potentially by limiting plaque chemokine production.

Aims: The interleukin-1 receptor accessory protein (IL1RAP) is a co-receptor required for signalling through the IL-1, IL-33, and IL-36 receptors. Using a novel anti-IL1RAP-blocking antibody, we investigated the role of IL1RAP in atherosclerosis. Methods and results: Single-cell RNA sequencing data from human atherosclerotic plaques revealed the expression of IL1RAP and several IL1RAP-related cytokines and receptors, including IL1B and IL33. Histological analysis showed the presence of IL1RAP in both the plaque and adventitia, and flow cytometry of murine atherosclerotic aortas revealed IL1RAP expression on plaque leucocytes, including neutrophils and macrophages. High-cholesterol diet fed apolipoprotein E-deficient (Apoe-/-) mice were treated with a novel non-depleting IL1RAP-blocking antibody or isotype control for the last 6 weeks of diet. IL1RAP blockade in mice resulted in a 20% reduction in subvalvular plaque size and limited the accumulation of neutrophils and monocytes/macrophages in plaques and of T cells in adventitia, compared with control mice. Indicative of reduced plaque inflammation, the expression of several genes related to leucocyte recruitment, including Cxcl1 and Cxcl2, was reduced in brachiocephalic arteries of anti-IL1RAP-treated mice, and the expression of these chemokines in human plaques was mainly restricted to CD68+ myeloid cells. Furthermore, in vitro studies demonstrated that IL-1, IL-33, and IL-36 induced CXCL1 release from both macrophages and fibroblasts, which could be mitigated by IL1RAP blockade. Conclusion: Limiting IL1RAP-dependent cytokine signalling pathways in atherosclerotic mice reduces plaque burden and plaque inflammation, potentially by limiting plaque chemokine production.

Genome-wide association studies (GWASs) have uncovered susceptibility loci associated with psychiatric disorders such as bipolar disorder (BP) and schizophrenia (SCZ). However, most of these loci are in non-coding regions of the genome, and the causal mechanisms of the link between genetic variation and disease risk is unknown. Expression quantitative trait locus (eQTL) analysis of bulk tissue is a common approach used for deciphering underlying mechanisms, although this can obscure cell-type-specific signals and thus mask trait-relevant mechanisms. Although single-cell sequencing can be prohibitively expensive in large cohorts, computationally inferred cell-type proportions and cell-type gene expression estimates have the potential to overcome these problems and advance mechanistic studies. Using bulk RNA-seq from 1,730 samples derived from whole blood in a cohort ascertained from individuals with BP and SCZ, this study estimated cell-type proportions and their relation with disease status and medication. For each cell type, we found between 2,875 and 4,629 eGenes (genes with an associated eQTL), including 1,211 that are not found on the basis of bulk expression alone. We performed a colocalization test between cell-type eQTLs and various traits and identified hundreds of associations that occur between cell-type eQTLs and GWASs but that are not detected in bulk eQTLs. Finally, we investigated the effects of lithium use on the regulation of cell-type expression loci and found examples of genes that are differentially regulated according to lithium use. Our study suggests that applying computational methods to large bulk RNA-seq datasets of non-brain tissue can identify disease-relevant, cell-type-specific biology of psychiatric disorders and psychiatric medication.

Human biomonitoring can add value to chemical risk assessment by reducing the assumptions regarding consumption rates, residue occurrence, and processing effects and by integrating exposures from different sources (diet, household use, environmental). However, the relationship between exposure and concentration in human matrices is unknown for most pesticides. Therefore, we conducted a pilot study to gain more insight into the qualitative and quantitative relationship between dietary intake of pesticides (external exposure) and urinary excretion (reflecting internal exposure). In this cross-sectional observational study, 35 healthy consumers aged 18–65 years from the region of Wageningen, Netherlands, collected an exact duplicate portion of their diets during 24 h. On the same day, they also collected all their urine. The duplicate diets were analyzed using target screening by GC- and LC-HRMS; each duplicate diet contained at least five, up to 21, pesticide residues. The 24 h urine samples were analyzed using LC-HRMS in a suspect screening workflow. Metabolites were tentatively detected in all 24 h urine samples, ranging from six metabolites corresponding to four pesticides up to 40 metabolites originating from 16 pesticides in a single urine sample. In total, 65 metabolites originating from 28 pesticides were tentatively detected. After prioritization and additional confirmation experiments, 28 metabolites originating from 10 pesticides were identified with confidence level 1 or 2b. Next, quantitative analysis was performed for a selection of pesticides in duplicate diets and their metabolites in 24 h urine to assess quantitative relationships. In the quantitative comparisons between duplicate diet and 24 h urine, it was found that some metabolites were already present in the duplicate diet, which may give an overestimation of exposure to the parent pesticide based on measurement of the metabolites in urine. Additionally, the quantitative comparisons suggest a back

BACKGROUND: Identifying the dorsolateral subthalamic nucleus (STN) for deep brain stimulation (DBS) in Parkinson's disease (PD) can be challenging due to the size and double-oblique orientation. Since 2015 we implemented 7-Tesla T2 weighted magnetic resonance imaging (7 T T2) for improving visualization and targeting of the dorsolateral STN. We describe the changes in surgical planning and outcome since implementation of 7 T T2 for DBS in PD.METHODS: By comparing two cohorts of STN DBS patients in different time periods we evaluated the influence of 7 T T2 on STN target planning, the number of microelectrode recording (MER) trajectories, length of STN activity and the postoperative motor (UPDRS) improvement.RESULTS: From February 2007 to January 2014, 1.5 and 3-Tesla T2 guided STN DBS with 3 MER channels was performed in 76 PD patients. Average length of recorded STN activity in the definite electrode trajectory was 3.9 ± 1.5 mm. From January 2015 to January 2022 7 T T2 and MER-guided STN DBS was performed in 182 PD patients. Average length of recorded STN activity in the definite electrode trajectory was 5.1 ± 1.3 mm and used MER channels decreased from 3 to 1. Average UPDRS improvement was comparable.CONCLUSION: Implementation of 7 T T2 for STN DBS enabled a refinement in targeting. Combining classical DBS targeting with dorsolateral STN alignment may be used to determine the optimal trajectory. The improvement in dorsolateral STN visualization can be used for further target refinements, for example adding probabilistic subthalamic connectivity, to enhance clinical outcome of STN DBS.

In this article, we study the phase behavior of two polydisperse hydrocolloids: dextran and polyethylene oxide. We combine the data on the experimental osmometric virial coefficients of the pure components with the experimental critical point of their aqueous mixture and the size distribution of each component from a previously published study in order to predict the phase boundary, spinodal, and fractionation upon demixing of the polydisperse mixture. We compare the results of our calculation to the experimental phase diagram. Our method reveals a better correspondence with the experimental binary phase behavior than modeling each component as monodisperse. The polydispersity of the hydrocolloids causes the phase separation boundary to shift to lower concentrations and the miscibility region to decrease and change its shape from a rotated U-shape to a W-shape.

A key step in preparing industrial data for multivariate statistical modelling of (batch-)continuous processes is the estimation of sensor delays along the production line, to use as a correction for understanding relationships between them. Without such a correction, the measurements collected from the sensors do not all relate to the same portion of material travelling through the plant, which is where from a physical point of view the correlations are expected to arise from. Most methods to do these corrections currently reported in literature are limited in that they optimize only correlations bivariately between the different sensors, despite the eventual goal of being understood as a multivariate process model. This work proposes several methods for multivariate sensor delay estimation, based on multivariate projection methods, and critically investigates these using simulated and empirical process data from two industrial facilities. The objective is to provide more clarity on if, how, and why taking into account these multivariate correlations using such projection methods is beneficial. One of the proposed methods, named PLS-SEQ, was shown to outperform bivariate sensor delay estimation, which is regarded as benchmark method in this work, for all datasets. The average reduction in delay estimation error achieved by using PLS-SEQ is between 6% and 64%. The other newly proposed multivariate projection-based methods did not show such unanimous improvement in accuracy, but helped identifying the presence of sensor clusters in industrial data as a novel key challenge for sensor delay estimation. The presented results illustrate that projection-based multivariate methods, in particular the newly proposed method PLS-SEQ, show promising potential for sensor delay estimation, outperforming the bivariate sensor delay estimation methods used as benchmark. Ultimately, using these methods can improve the predictive and descriptive quality of statistical models for key i

Understanding the physical processes that regulate star formation and galaxy evolution are major areas of activity in modern astrophysics. Nearby galaxies offer unique opportunities to inspect interstellar medium (ISM), star formation (SF), radiative, dynamic and magnetic physics in great detail from sub-galactic (kpc) scales to sub-cloud (sub-pc) scales, from quiescent galaxies to starbursts, and from field galaxies to overdensities. In this case study, we discuss the major breakthroughs in this area of research that will be enabled by the Atacama Large Aperture Submillimeter Telescope (AtLAST), a proposed 50-m single-dish submillimeter telescope. The new discovery space of AtLAST comes from its exceptional sensitivity, in particular to extended low surface brightness emission, a very large 2 degree field of view, and correspondingly high mapping efficiency. This paper focuses on four themes which will particularly benefit from AtLAST: 1) the LMC and SMC, 2) extragalactic magnetic fields, 3) the physics and chemistry of the interstellar medium, and 4) star formation and galaxy evolution. With ~1000-2000h surveys each, AtLAST could deliver deep dust continuum maps of the entire LMC and SMC fields at parsec-scale resolution, high-resolution maps of the magnetic field structure, gas density, temperature and composition of the dense and diffuse ISM in ~100 nearby galaxies, as well as the first large-scale blind CO survey in the nearby Universe, delivering molecular gas masses for up to 10^6 galaxies (3 orders of magnitude more than current samples). Through such observing campaigns, AtLAST will have a profound impact on our understanding of the baryon cycle and star formation across a wide range of environments., Comment: 29 pages, 11 figues, submitted to Open Research Europe as part of the AtLAST collection: https://open-research-europe.ec.europa.eu/collections/atlast/about

As we learn more about the multi-scale interstellar medium (ISM) of our Galaxy, we develop a greater understanding for the complex relationships between the large-scale diffuse gas and dust in Giant Molecular Clouds (GMCs), how it moves, how it is affected by the nearby massive stars, and which portions of those GMCs eventually collapse into star forming regions. The complex interactions of those gas, dust and stellar populations form what has come to be known as the ecology of our Galaxy. Because we are deeply embedded in the plane of our Galaxy, it takes up a significant fraction of the sky, with complex dust lanes scattered throughout the optically recognisable bands of the Milky Way. These bands become bright at (sub-)millimetre wavelengths, where we can study dust thermal emission and the chemical and kinematic signatures of the gas. To properly study such large-scale environments, requires deep, large area surveys that are not possible with current facilities. Moreover, where stars form, so too do planetary systems, growing from the dust and gas in circumstellar discs, to planets and planetesimal belts. Understanding the evolution of these belts requires deep imaging capable of studying belts around young stellar objects to Kuiper belt analogues around the nearest stars. Here we present a plan for observing the Galactic Plane and circumstellar environments to quantify the physical structure, the magnetic fields, the dynamics, chemistry, star formation, and planetary system evolution of the galaxy in which we live with AtLAST; a concept for a new, 50m single-dish sub-mm telescope with a large field of view which is the only type of facility that will allow us to observe our Galaxy deeply and widely enough to make a leap forward in our understanding of our local ecology., Comment: 27 pages, submitted to Open Research Europe as part of the AtLAST collection: https://open-research-europe.ec.europa.eu/collections/atlast/about

This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring the availability of posttreatment MR imaging encompassing T2-weighted and T1-weighted images (pre- and post-intravenous gadolinium administration). Qualitative features and quantitative measurements were independently scored by experienced radiologists, with deep learning segmentation aiding total eye volume assessment. Eyes were categorized into three groups: eyes receiving SIAC (Rb-SIAC), eyes treated with other eye-saving methods (Rb-control), and healthy eyes. The most prevalent adverse effects post-SIAC were inflammatory and vascular features, with therapy-induced contrast enhancement observed in the intraorbital optic nerve segment in 6% of patients. Quantitative analysis revealed significant growth arrest in Rb-SIAC eyes, particularly when treatment commenced ≤ 12 months of age. Optic nerve atrophy was a significant complication in Rb-SIAC eyes. In conclusion, this study highlights the vascular and inflammatory adverse effects observed post-SIAC in retinoblastoma patients and demonstrates a negative impact on eye and optic nerve growth, particularly in children treated ≤ 12 months of age, providing crucial insights for clinical management and future research.

An advanced coupling between a three-dimensional ocean circulation model (CROCO) and a spectral wave model (WAVEWATCH-III) is presented to better represent the interactions of macro-tidal currents with winds and waves. In the previous implementation of the coupled interface between these two models, some of the wave-induced terms in the ocean dynamic equations were computed from their monochromatic approximations (e.g. Stokes drift, Bernoulli head, near-bottom wave orbital velocity, wave-to-ocean energy flux). In the present study, the exchanges of these fields computed from the spectral wave model are implemented and evaluated. A set of numerical experiments for a coastal configuration of the macro-tidal circulation off the Bay of Somme (France) is designed. The impact of the spectral versus monochromatic computation of wave-induced terms has a notable effect on the macro-tidal hydrodynamics, particularly in scenarios involving storm waves and opposing winds to tidal flows. This effect manifests as a reduction in the wave-induced deceleration of the vertical profile of tidal currents. The new implementation provides current magnitudes closer to measurements than those predicted using monochromatic formulations, particularly at the free surface. The spectral-surface Stokes drift and the near-bottom wave orbital velocity are found to be the spectral fields with the most impact, respectively increasing advection towards the free surface and shifting the profile close to the seabed. In the particular case of the Bay of Somme, the approximation of these spectral terms with their monochromatic counterparts ultimately results in an underestimation of ocean surface currents. Our model developments thus provide a better description of the competing effects of tides, winds, and waves on the circulation off macro-tidal bays, with implications for the study of air–sea interactions and sediment transport processes.

Purpose: To describe a recessively inherited cerebral small vessel disease, caused by loss-of-function variants in Nitrilase1 (NIT1). Methods:We performed exome sequencing, brain magnetic resonance imaging, neuropathology, electron microscopy, western blotting, and transcriptomic and metabolic analyses in 7 NIT1-small vessel disease patients from 5 unrelated pedigrees. Results: The first identified patients were 3 siblings, compound heterozygous for the NIT1 c.727C>T; (p.Arg243Trp) variant and the NIT1 c.198_199del; p.(Ala68∗) variant. The 4 additional patients were single cases from 4 unrelated pedigrees and were all homozygous for the NIT1 c.727C>T; p.(Arg243Trp) variant. Patients presented in mid-adulthood with movement disorders. All patients had striking abnormalities on brain magnetic resonance imaging, with numerous and massively dilated basal ganglia perivascular spaces. Three patients had non-lobar intracerebral hemorrhage between age 45 and 60, which was fatal in 2 cases. Western blotting on patient fibroblasts showed absence of NIT1 protein, and metabolic analysis in urine confirmed loss of NIT1 enzymatic function. Brain autopsy revealed large electron-dense deposits in the vessel walls of small and medium sized cerebral arteries. Conclusion: NIT1-small vessel disease is a novel, autosomal recessively inherited cerebral small vessel disease characterized by a triad of movement disorders, massively dilated basal ganglia perivascular spaces, and intracerebral hemorrhage.

Robert B Bot,1,2 Razvan Chirla,1 Calin Tudor Hozan,1,2 Simona Cavalu1 1Faculty of Medicine and Pharmacy, University of Oradea, Oradea, 410087, Romania; 2Department of Orthopedics, Emergency County Clinical Hospital Oradea, Oradea, 410169, RomaniaCorrespondence: Simona Cavalu, Email scavalu@uoradea.roPurpose: The purpose of this study was to quantify the modifications occurring in osteoporosis at the level of the human proximal femur throughout the trabecular structure, along with the identification of certain anatomic regions preferentially affected by osteoporosis. Another goal was to map the evolution of the radiodensity of the trabecular bone as osteoporosis progresses to an advanced stage.Methods: The study included CT scans (right femur) from 51 patients, out of which 40 had various degrees of osteoporosis, but no other local pathology. Ten regions of interest in two orthogonal slices have been identified and the differences in radiodensity as well as their evolution have been statistically analyzed in terms of relative and absolute changes.Results: A detailed spatial map showing the evolution of osteoporosis was obtained. As osteoporosis evolved, the relative decrease in radiodensity was inversely correlated to the radiodensity of the healthy bone. In particular, the region covering the Ward triangle decreased the most, by an average 61– 62% in osteopenia and 101– 106% in advanced osteoporosis, while the principal compressive group was affected the least, showing a decrease by an average 14– 15% in osteopenia and 29– 32% in advanced osteoporosis. The absolute decrease in radiodensity was not correlated to the radiodensity of the healthy bone and was shifted to the inferior-posterior edge of the femur. Inside the femoral head, the upper region was affected the most in absolute terms, while the greater trochanter was less affected than the femoral neck. The maximum metaphyseal cortical bone density was unaffected by the progression of osteoporosis.Conclu

The size and shape of the Neandertal thorax has been debated since the first discovery of Neandertal ribs more than 150 years ago, with workers proposing different interpretations ranging from a Neandertal thoracic morphology that is indistinguishable from modern humans, to one that was significantly different from them. Here, we provide a virtual 3D reconstruction of the thorax of the adult male Kebara 2 Neandertal. Our analyses reveal that the Kebara 2 thorax is significantly different but not larger from that of modern humans, wider in its lower segment, which parallels his wide bi-iliac breadth, and with a more invaginated vertebral column. Kinematic analyses show that rib cages that are wider in their lower segment produce greater overall size increments (respiratory capacity) during inspiration. We hypothesize that Neandertals may have had a subtle, but somewhat different breathing mechanism compared to modern humans., Depto. de Biodiversidad, Ecología y Evolución, Fac. de Ciencias Biológicas, TRUE, pub

Supplementary Information accompanies this paper at https://doi.org/10.1038/s41467-019-09930-3. Competing interests: The authors declare no competing interests. Reprints and permission information is available online at http://npg.nature.com/reprintsandpermissions/ Journal peer review information: Nature Communications thanks the anonymousreviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available. Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations., Studying immune repertoire in the context of organ transplant provides important information on how adaptive immunity may contribute and modulate graft rejection. Here we characterize the peripheral blood immune repertoire of individuals before and after kidney transplant using B cell receptor sequencing in a longitudinal clinical study. Individuals who develop rejection after transplantation have a more diverse immune repertoire before transplant, suggesting a predisposition for post-transplant rejection risk. Additionally, over 2 years of follow-up, patients who develop rejection demonstrate a specific set of expanded clones that persist after the rejection. While there is an overall reduction of peripheral B cell diversity, likely due to increased general immunosuppression exposure in this cohort, the detection of specific IGHV gene usage across all rejecting patients supports that a common pool of immunogenic antigens may drive post-transplant rejection. Our findings may have clinical implications for the prediction and clinical management of kidney transplant rejection., Depto. de Estadística y Ciencia de los Datos, Fac. de Estudios Estadísticos, TRUE, pub

Encryption on the internet with the shift to HTTPS has been an important step to improve the privacy of internet users. However, there is an increasing body of work about extracting information from encrypted internet traffic without having to decrypt it. Such attacks bypass security guarantees assumed to be given by HTTPS and thus need to be understood. Prior works showed that the variable bitrates of video streams are sufficient to identify which video someone is watching. These works generally have to make trade-offs in aspects such as accuracy, scalability, robustness, etc. These trade-offs complicate the practical use of these attacks. To that end, we propose a deep metric learning framework based on the triplet loss method. Through this framework, we achieve robust, generalisable, scalable and transferable encrypted video stream detection. First, the triplet loss is better able to deal with video streams not seen during training. Second, our approach can accurately classify videos not seen during training. Third, we show that our method scales well to a dataset of over 1000 videos. Finally, we show that a model trained on video streams over Chrome can also classify streams over Firefox. Our results suggest that this side-channel attack is more broadly applicable than originally thought. We provide our code alongside a diverse and up-to-date dataset for future research., Comment: Published in the WI-IAT 2023 proceedings

Dimensionality reduction algorithms are often used to visualise high-dimensional data. Previously, studies have used prior information to enhance or suppress expected patterns in projections. In this paper, we adapt such techniques for domain knowledge guided interactive exploration. Inspired by Mapper and STAD, we present three types of lens functions for UMAP, a state-of-the-art dimensionality reduction algorithm. Lens functions enable analysts to adapt projections to their questions, revealing otherwise hidden patterns. They filter the modelled connectivity to explore the interaction between manually selected features and the data's structure, creating configurable perspectives each potentially revealing new insights. The effectiveness of the lens functions is demonstrated in two use cases and their computational cost is analysed in a synthetic benchmark. Our implementation is available in an open-source Python package: https://github.com/vda-lab/lensed_umap., Comment: 11 pages, 5 figures, submitted to IEEE Transactions on Visualization and Computer Graphics

Item does not contain fulltext

Item does not contain fulltext

Le droit de l’urbanisme a connu depuis le début des années 2000 de nombreuses et importantes réformes qui l’ont renouvelé en profondeur. Aux objectifs traditionnels de cette discipline (sécurité, salubrité, desserte par les réseaux, esthétisme) s’en sont ajoutés de nouveaux, au premier rang desquels figurent la construction de logements et la préservation de l’environnement. Tous les leviers ont été mobilisés à cette fin : les règles nationales, modifiées pour intégrer ces exigences ;les documents d’urbanisme, désormais soumis à évaluation environnementale et investis d’une mission de lutte contre l’artificialisation des sols et l’érosion côtière ; le droit de préemption, dont les finalités d’utilisation se sont trouvées élargies ; les autorisations d’urbanisme, délivrées plus rapidement et sécurisées afin d’accélérer la production de logements ; l’aménagement, mis au service du développement durable. Il en a résulté une multiplication des normes, des procédures et des régimes, qui met la règle au service d’un projet et favorise une adaptation de celle-ci à la diversité des situations, mais génère dans le même temps une sophistication extrêmement poussée du droit de l’urbanisme et, par là-même, une réelle complexité de celui-ci. L’ambition de cet ouvrage est de favoriser l’accès à ce droit et sa compréhension en en faisant un outil directement opérationnel. Toutes les règles d’urbanisme y sont regroupées, y compris celles présentes dans d’autres codes, éclairées par les jurisprudences, circulaires et réponses ministérielles pertinentes. La règle est analysée dans son contenu, son fondement, sa portée et ses limites. De nombreux exemples et définitions sont mentionnés. À la recherche de sécurité juridique, le lecteur pourra accéder rapidement à une analyse fiable et se déterminer en fonction de celle-ci. L’ouvrage s’adresse tout particulièrement aux professionnels de l’immobilier, notamment les services juridiques et d’urbanisme des collectivités locales, services ce

Introducción. La ciudad y la naturaleza urbana. Madrid y la importancia de su flora Metodología. ¿Cómo saber qué plantas silvestres viven dentro de una ciudad? Resultados. Las grandes cifras de la flora madrileña Lista roja. Las especies en peligro del Madrid Urbano: ensayo metodológico y lista roja Especies autóctonas. Las plantas madrileñas más frecuentes Especies alóctonas. Las plantas madrileñas más frecuentes Ornamentales. El origen de la flora ornamental de Madrid Análisis. ¿Qué nos dicen los datos? Análisis de los resultados Perturbaciones. Perturbaciones y procesos de extinción en los entornos urbanos Recomendaciones. Recomendaciones generales para una gestión de la flora y la vegetación madrileñas Plan de Biodiversidad. El Plan de Biodiversidad madrileño y la flora urbana de la ciudad Epílogo. Declaración botánica de Madrid Anexos: I. Catálogo de la flora vascular del Madrid Urbano. I I . Listado de especies ornamentales presentes en Madrid.I I I . Bibliografía de la BFCMU. Índices

Encryption on the internet with the shift to HTTPS has been an important step to improve the privacy of internet users. However, there is an increasing body of work about extracting information from encrypted internet traffic without having to decrypt it. Such attacks bypass security guarantees assumed to be given by HTTPS and thus need to be understood. Prior works showed that the variable bitrates of video streams are sufficient to identify which video someone is watching. These works generally have to make trade-offs in aspects such as accuracy, scalability, robustness, etc. These trade-offs complicate the practical use of these attacks. To that end, we propose a deep metric learning framework based on the triplet loss method. Through this framework, we achieve robust, generalisable, scalable and transferable encrypted video stream detection. First, the triplet loss is better able to deal with video streams not seen during training. Second, our approach can accurately classify videos not seen during training. Third, we show that our method scales well to a dataset of over 1000 videos. Finally, we show that a model trained on video streams over Chrome can also classify streams over Firefox. Our results suggest that this side-channel attack is more broadly applicable than originally thought. We provide our code alongside a diverse and up-to-date dataset for future research.

Insight in the way verbal teacher-student classroom interaction unfolds during the language lesson is of crucial importance for effective teaching. Although classroom observational research is indispensable, it is unable to uncover underlying intentions or motivations for the observed behavior. Teacher cognition research seeks to address the relation between teaching practice and what teachers think. This study reports on the perceptions of a group of English as a foreign language teachers (n = 57) who were asked to reflect on results from a classroom observation study about EFL teacher-student interaction in a similar teaching context. A large majority (82%) of the respondents recognized the observed pattern of closed teacher questions and limited student responses. This majority indicated that student participation in their own lessons is similar to the observed lessons or lower. Respondents attributed the pattern of high teacher activity and low student activity to emotional factors rather than to students' proficiency levels, lesson content, lesson activities or motivational aspects. According to 51% of the respondents, making students feel more competent by focusing on formative evaluation might improve classroom interaction, whereas 18% of the respondents suggested that interaction could be improved by using different teaching materials.

Item does not contain fulltext, INTRODUCTION: Medical students regularly transition between clerkships. These transitions can lead to discontinuity in their development because of the need to adapt to a new environment. The use of entrustable professional activities (EPAs) might facilitate less disruptive transitions across clerkships, as they could provide support at the start of a clerkship. This study aims to shed light on how an EPA-based curriculum contributes to medical students' learning processes during transitions. METHODS: The authors used a constructivist rapid ethnographic design. They conducted observations and interviews with 11 medical students in their Pediatrics clerkship; six of them were in clerkships not utilizing EPAs, and five were using EPAs. Data collection was followed by template analysis such that all data were coded with a template that was continually updated until the authors all agreed upon a definitive template. RESULTS: Four themes proved important when considering the impact of EPAs during transitions between clerkships: transitions as a learning opportunity, building relationships in context, taking leadership in the landscape of practice and feedback-seeking behavior. DISCUSSION: EPAs smooth clerkship transitions, as they establish continuity in the student's development and facilitate navigating discontinuity in transitions. Students build skills and confidence in order to grow and work with increasing independence within the clerkships. Transitions offer important learning opportunities for students, which can be fully exploited by using EPA guidance.

01 april 2023, Item does not contain fulltext, PURPOSE: To relate [(18)F]fluoride uptake on PET with abnormalities on magnetic resonance imaging (MRI) and conventional radiography (CR) in ankylosing spondylitis (AS) patients. METHODS: Ten clinically active AS patients (female 6/10, age 38 ± 11 years) were included, and both spine and SI-joints were examined. PET scans were dichotomously scored for enhanced [(18)F]fluoride uptake, MRI scans were scored for fatty lesions, erosions, ankylosis, and bone marrow edema (BME), and CR was scored for erosions, syndesmophytes, and ankylosis. The overlap of lesions across all modalities was evaluated through univariate and multivariate analyses using a generalized mixed model. RESULTS: In the spine, 69 lesions with enhanced [(18)F]fluoride uptake, 257 MRI lesions, and 88 CR lesions were observed. PET lesions were mostly located in costovertebral and facet joints, outside the field of view (FOV) of the MRI and CR. However, PET lesions inside the FOV of MRI and CR partially showed no abnormality on MRI and CR. In lesions with abnormalities on multiple modalities, both univariate and multivariate analysis showed that PET activity had the strongest association with BME on MRI and ankylosis on CR. In the SI joints, 15 lesions (75%) with PET uptake were found, with 87% showing abnormalities on MRI and CR. CONCLUSION: [(18)F]fluoride PET lesions are often found outside the scope of MRI and CR, and even in the same location show only partial overlap with abnormalities on MRI (especially BME) and CR (especially ankylosis). This suggests that [(18)F]fluoride PET partially visualizes aspects of AS separate from MRI and CR, providing novel information. CLINICAL TRIAL REGISTRATION: NL43223.029.13 registered at 02-05-2013. https://www.toetsingonline.nl/to/ccmo_search.nsf/fABRpop?readform&unids=C1257BA2002CC066C1257B4E0049A65A.

01 april 2023, Item does not contain fulltext, PURPOSE: To relate [(18)F]fluoride uptake on PET with abnormalities on magnetic resonance imaging (MRI) and conventional radiography (CR) in ankylosing spondylitis (AS) patients. METHODS: Ten clinically active AS patients (female 6/10, age 38 ± 11 years) were included, and both spine and SI-joints were examined. PET scans were dichotomously scored for enhanced [(18)F]fluoride uptake, MRI scans were scored for fatty lesions, erosions, ankylosis, and bone marrow edema (BME), and CR was scored for erosions, syndesmophytes, and ankylosis. The overlap of lesions across all modalities was evaluated through univariate and multivariate analyses using a generalized mixed model. RESULTS: In the spine, 69 lesions with enhanced [(18)F]fluoride uptake, 257 MRI lesions, and 88 CR lesions were observed. PET lesions were mostly located in costovertebral and facet joints, outside the field of view (FOV) of the MRI and CR. However, PET lesions inside the FOV of MRI and CR partially showed no abnormality on MRI and CR. In lesions with abnormalities on multiple modalities, both univariate and multivariate analysis showed that PET activity had the strongest association with BME on MRI and ankylosis on CR. In the SI joints, 15 lesions (75%) with PET uptake were found, with 87% showing abnormalities on MRI and CR. CONCLUSION: [(18)F]fluoride PET lesions are often found outside the scope of MRI and CR, and even in the same location show only partial overlap with abnormalities on MRI (especially BME) and CR (especially ankylosis). This suggests that [(18)F]fluoride PET partially visualizes aspects of AS separate from MRI and CR, providing novel information. CLINICAL TRIAL REGISTRATION: NL43223.029.13 registered at 02-05-2013. https://www.toetsingonline.nl/to/ccmo_search.nsf/fABRpop?readform&unids=C1257BA2002CC066C1257B4E0049A65A.

The northwestern Tropical Atlantic Ocean is a turbulent region, filled with mesoscale eddies and regional currents. In this intense dynamical context, several water masses with thermohaline characteristics of different origins are advected, mixed, and stirred at the surface and at depth. The EUREC4A-OA/ATOMIC experiment that took place in January and February 2020 was dedicated to assessing the processes at play in this region, especially the interaction between the ocean and the atmosphere. For that reason, four oceanographic vessels and different autonomous platforms measured properties near the air–sea interface and acquired thousands of upper-ocean (up to 400–2000 m depth) profiles. However, each device had its own observing capability, varying from deep measurements acquired during vessel stations to shipboard underway near-surface observations and measurements from autonomous and uncrewed systems (such as Saildrones). These observations were undertaken with a specific sampling strategy guided by near-real-time satellite maps and adapted every half day, based on the process that was investigated. These processes were characterized by different spatiotemporal scales, from mesoscale eddies, with diameters exceeding 100 km, to submesoscale filaments of 1 km width. This article describes the datasets gathered from the different devices and how the data were calibrated and validated. In order to ensure an overall consistency, the platforms' datasets are cross-validated using a hierarchy of instruments defined by their own specificity and calibration procedures. This has enabled the quantification of the uncertainty in the measured parameters when different datasets are used together, e.g., https://doi.org/10.17882/92071 (L'Hégaret et al., 2020a).

Contains fulltext : 294768.pdf (Publisher’s version ) (Closed access), Although the best-known spinocerebellar ataxias (SCAs) are triplet repeat diseases, many SCAs are not caused by repeat expansions. The rarity of individual non-expansion SCAs, however, has made it difficult to discern genotype-phenotype correlations. We therefore screened individuals who had been found to bear variants in a non-expansion SCA-associated gene through genetic testing, and after we eliminated genetic groups that had fewer than 30 subjects, there were 756 subjects bearing single-nucleotide variants or deletions in one of seven genes: CACNA1A (239 subjects), PRKCG (175), AFG3L2 (101), ITPR1 (91), STUB1 (77), SPTBN2 (39), or KCNC3 (34). We compared age at onset, disease features, and progression by gene and variant. There were no features that reliably distinguished one of these SCAs from another, and several genes-CACNA1A, ITPR1, SPTBN2, and KCNC3-were associated with both adult-onset and infantile-onset forms of disease, which also differed in presentation. Nevertheless, progression was overall very slow, and STUB1-associated disease was the fastest. Several variants in CACNA1A showed particularly wide ranges in age at onset: one variant produced anything from infantile developmental delay to ataxia onset at 64 years of age within the same family. For CACNA1A, ITPR1, and SPTBN2, the type of variant and charge change on the protein greatly affected the phenotype, defying pathogenicity prediction algorithms. Even with next-generation sequencing, accurate diagnosis requires dialogue between the clinician and the geneticist.

The northwestern Tropical Atlantic Ocean is a turbulent region, filled with mesoscale eddies and regional currents. In this intense dynamical context, several water masses with thermohaline characteristics of different origins are advected, mixed, and stirred at the surface and at depth. The EUREC4A-OA/ATOMIC experiment that took place in January and February 2020 was dedicated to assessing the processes at play in this region, especially the interaction between the ocean and the atmosphere. For that reason, four oceanographic vessels and different autonomous platforms measured properties near the air–sea interface and acquired thousands of upper-ocean (up to 400–2000 m depth) profiles. However, each device had its own observing capability, varying from deep measurements acquired during vessel stations to shipboard underway near-surface observations and measurements from autonomous and uncrewed systems (such as Saildrones). These observations were undertaken with a specific sampling strategy guided by near-real-time satellite maps and adapted every half day, based on the process that was investigated. These processes were characterized by different spatiotemporal scales, from mesoscale eddies, with diameters exceeding 100 km, to submesoscale filaments of 1 km width. This article describes the datasets gathered from the different devices and how the data were calibrated and validated. In order to ensure an overall consistency, the platforms' datasets are cross-validated using a hierarchy of instruments defined by their own specificity and calibration procedures. This has enabled the quantification of the uncertainty in the measured parameters when different datasets are used together, e.g., https://doi.org/10.17882/92071 (L'Hégaret et al., 2020a).

Item does not contain fulltext

Contains fulltext : 299603.pdf (Publisher’s version ) (Open Access), BACKGROUND: Antimicrobial stewardship (AMS), the set of actions to ensure antibiotics are used appropriately, is increasingly targeted at all those involved in the antimicrobial pathway, including nurses. Several healthcare organizations have issued position statements on how bedside nurses can be involved in AMS. However, it remains unclear how nurses, in reality, contribute to appropriate antibiotic use. OBJECTIVES: To systematically search the literature to describe the activities bedside nurses perform regarding antibiotic use in daily clinical practice, in relation to the activities proposed by the aforementioned position statements. METHODS: We searched MEDLINE, Embase, CINAHL and grey literature until March 2021. Studies were included if they described activities regarding antibiotic use performed by bedside nurses. Methodological rigour was assessed by applying the Mixed Method Appraisal Tool. RESULTS: A total of 118 studies were included. The majority of the proposed nurses' activities were found in daily practice, categorized into assessment of clinical status, collection of specimens, management of antimicrobial medication, prompting review and educating patient and relatives. Nurses may take the lead in these clinical processes and are communicators in all aspects of the antimicrobial pathway. Patient advocacy appears to be a strong driver of bedside nurses' activities. CONCLUSIONS: Nurses' activities are already integrated in the day-to-day nursing practice and are grounded in the essence of nursing, being a patient advocate and showing nursing leadership in safeguarding the antimicrobial treatment process. An essential element of the nursing role is communication with other stakeholders in the patient-centred antimicrobial pathway. Educating, engaging and empowering nurses in this already integrated role, could lead to a solid, impactful nursing contribution to AMS., 01 december 2023

This article analyzes Drucilla Cornell’s critical theory as a practice of engaging with radical thinking and radical politics in the interest of revolutionary transformation. Arguing that Walter Benjamin’s imperative to wrest tradition away from conformism is at the heart of Cornell’s work, the article shows how Cornell applies this imperative both to the tradition of resistance against oppression and to critical theory itself. The article follows Cornell’s call to decolonize the critical theoretical project by bringing Surinamese anticolonial activist and writer Anton de Kom, various collectives that participated in the 2022 German art festival documenta 15, and the disobedience of six young Palestinian “Freedom Riders” into conversation with Cornell’s writings on the South African Revolution and on Afro-Caribbean liberatory thought.

Encryption on the internet with the shift to HTTPS has been an important step to improve the privacy of internet users. However, there is an increasing body of work about extracting information from encrypted internet traffic without having to decrypt it. Such attacks bypass security guarantees assumed to be given by HTTPS and thus need to be understood. Prior works showed that the variable bitrates of video streams are sufficient to identify which video someone is watching. These works generally have to make trade-offs in aspects such as accuracy, scalability, robustness, etc. These trade-offs complicate the practical use of these attacks. To that end, we propose a deep metric learning framework based on the triplet loss method. Through this framework, we achieve robust, generalisable, scalable and transferable encrypted video stream detection. First, the triplet loss is better able to deal with video streams not seen during training. Second, our approach can accurately classify videos not seen during training. Third, we show that our method scales well to a dataset of over 1000 videos. Finally, we show that a model trained on video streams over Chrome can also classify streams over Firefox. Our results suggest that this side-channel attack is more broadly applicable than originally thought. We provide our code alongside a diverse and up-to-date dataset for future research.

Mobility of the sedimentary substrate, both through the flow of sedimentary particles and through the migration and evolution of sedimentary structures, has direct implications on the design, implementation, longevity, and safety of ORE (ocean renewable energy) devices. Marine dunes are very present on the English Channel and North Sea coast where most of the future Europeans offshore windfarms (OWF) are located and planned to be constructed. Cable installation and foundations for OWF in this environment is a challenge due to the seabed mobility. This mobility can bring risks of cable over-burying or un-burying and uncertainties about foundations scouring conditions. Consequently, there is a need to anticipate variations in sediment thickness to limit damage to infrastructure and to design anti-scouring protection and better anticipate OWF costs. Furthermore, marine dunes are areas of high ecological importance. It is therefore important to understand the effect that the installation of MRE infrastructure can have on dune morphodynamics to limit the impacts on the ecosystem. To address all these issues for OWF industry, two research and development collaborative projects have been set up: DUNES & MODULLES. The first project (DUNES) aimed at collecting in situ data on seabed, hydrodynamics and ecosystem via bathymetric surveys, current measurements and biological sampling. The second one (MODULLES) aims to model the influence of these dunes on offshore wind farms at different spatio-temporal scales from a few seconds and centimeters to several years and kilometers via numerical and physical modeling. During MARID, marine dunes issues for ORE sector will be depicted. An overview of the DUNES and MODULES projects will be given to present how we address these issues with research and development project.

The northwestern Tropical Atlantic Ocean is a turbulent region, filled with mesoscale eddies and regional currents. In this intense dynamical context, several water masses with thermohaline characteristics of different origins are advected, mixed, and stirred at the surface and at depth. The EUREC4A-OA/ATOMIC experiment that took place in January and February 2020 was dedicated to assessing the processes at play in this region, especially the interaction between the ocean and the atmosphere. For that reason, four oceanographic vessels and different autonomous platforms measured properties near the air–sea interface and acquired thousands of upper-ocean (up to 400–2000 m depth) profiles. However, each device had its own observing capability, varying from deep measurements acquired during vessel stations to shipboard underway near-surface observations and measurements from autonomous and uncrewed systems (such as Saildrones). These observations were undertaken with a specific sampling strategy guided by near-real-time satellite maps and adapted every half day, based on the process that was investigated. These processes were characterized by different spatiotemporal scales, from mesoscale eddies, with diameters exceeding 100 km, to submesoscale filaments of 1 km width. This article describes the datasets gathered from the different devices and how the data were calibrated and validated. In order to ensure an overall consistency, the platforms' datasets are cross-validated using a hierarchy of instruments defined by their own specificity and calibration procedures. This has enabled the quantification of the uncertainty in the measured parameters when different datasets are used together, e.g., https://doi.org/10.17882/92071 (L'Hégaret et al., 2020a).