Cartan subalgebras in C*-algebras of Hausdorff etale groupoids

The reduced $C^*$-algebra of the interior of the isotropy in any Hausdorff \'etale groupoid $G$ embeds as a $C^*$-subalgebra $M$ of the reduced $C^*$-algebra of $G$. We prove that the set of pure states of $M$ with unique extension is dense, and deduce that any representation of the reduced $C^*$-algebra of $G$ that is injective on $M$ is faithful. We prove that there is a conditional expectation from the reduced $C^*$-algebra of $G$ onto $M$ if and only if the interior of the isotropy in $G$ is closed. Using this, we prove that when the interior of the isotropy is abelian and closed, $M$ is a Cartan subalgebra. We prove that for a large class of groupoids $G$ with abelian isotropy---including all Deaconu--Renault groupoids associated to discrete abelian groups---$M$ is a maximal abelian subalgebra. In the specific case of $k$-graph groupoids, we deduce that $M$ is always maximal abelian, but show by example that it is not always Cartan.Comment: 14 pages. v2: Theorem 3.1 in v1 incorrect (thanks to A. Kumjain for pointing out the error); v2 shows there is a conditional expectation onto $M$ iff the interior of the isotropy is closed. v3: Material (including some theorem statements) rearranged and shortened. Lemma~3.5 of v2 removed. This version published in Integral Equations and Operator Theor

Severe Paediatric Asthma Collaborative in Europe (SPACE):protocol for a European registry

The development of new asthma biologics and receptor blockers for the treatment of paediatric severe asthma raises challenges. It is unclear whether there are sufficient children in Europe to recruit into randomised placebo-controlled trials to establish efficacy and safety in this age group. In February 2016, the European Respiratory Society funded a clinical research collaboration entitled “Severe Paediatric Asthma Collaborative in Europe” (SPACE). We now report the SPACE protocol for a prospective pan-European observational study of paediatric severe asthma. Inclusion criteria are: 1) age 6–17 years, 2) severe asthma managed at a specialised centre for ≥6 months, 3)clinical and spirometry evidence of asthma, and 4) reaching a pre-defined treatment threshold. The exclusion criterion is the presence of conditions which mimic asthma symptoms. Eligible children will be prospectively recruited into a registry, recording demographics, comorbidities, quality of life, family history, neonatal history, smoking history, asthma background, investigations, and treatment. Follow-up will provide longitudinal data on asthma control and treatment changes. The SPACE registry, by identifying well-phenotyped children eligible for clinical trials, and the amount of overlap in eligibility criteria, will inform the design of European trials in paediatric severe asthma, and facilitate observational research where data from single centres are limited

The Use of Handheld Ultrasound Devices-An EFSUMB Position Paper

Publisher Copyright: © 2018 Georg Thieme Verlag KG Stuttgart New York.The miniaturization of ultrasound equipment in the form of tablet-or smartphone-sized ultrasound equipment is a result of the rapid evolution of technology and handheld ultrasound devices (HHUSD). This position paper of the European Federation of Societies in Ultrasound and Medicine (EFSUMB) assesses the current status of HHUSD in abdominal ultrasound, pediatric ultrasound, targeted echocardiography and heart ultrasound, and we will report position comments on the most common clinical applications. Also included is a SWOT (Strength-Weaknesses-Opportunities-Threats) analysis, the use for handheld devices for medical students, educational & training aspects, documentation, storage and safety considerations.Peer reviewe

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

First analysis of the Severe Paediatric Asthma Collaborative in Europe registry.

New biologics are being continually developed for paediatric asthma, but it is unclear whether there are sufficient numbers of children in Europe with severe asthma and poor control to recruit to trials needed for registration. To address these questions, the European Respiratory Society funded the Severe Paediatric Asthma Collaborative in Europe (SPACE), a severe asthma registry. We report the first analysis of the SPACE registry, which includes data from 10 paediatric respiratory centres across Europe. Data from 80 children with a clinical diagnosis of severe asthma who were receiving both high-dose inhaled corticosteroid and long-acting β2-agonist were entered into the registry between January 2019 and January 2020. Suboptimal control was defined by either asthma control test, or Global Initiative for Asthma criteria, or ≥2 severe exacerbations in the previous 12 months, or a combination. Overall, 62 out of 80 (77%) children had suboptimal asthma control, of whom 29 were not prescribed a biologic. However, in 24 there was an option for starting a licensed biologic. 33 children with suboptimal control were prescribed a biologic (omalizumab (n=24), or mepolizumab (n=7), or dupilumab (n=2)), and for 29 there was an option to switch to a different biologic. We conclude that the SPACE registry provides data that will support the planning of studies of asthma biologics. Not all children on biologics achieve good asthma control, and there is need for new trial designs addressing biologic switching

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment