Using the data quality dashboard to improve the ehden network

Federated networks of observational health databases have the potential to be a rich resource to inform clinical practice and regulatory decision making. However, the lack of standard data quality processes makes it difficult to know if these data are research ready. The EHDEN COVID-19 Rapid Collaboration Call presented the opportunity to assess how the newly developed open-source tool Data Quality Dashboard (DQD) informs the quality of data in a federated network. Fifteen Data Partners (DPs) from 10 different countries worked with the EHDEN taskforce to map their data to the OMOP CDM. Throughout the process at least two DQD results were collected and compared for each DP. All DPs showed an improvement in their data quality between the first and last run of the DQD. The DQD excelled at helping DPs identify and fix conformance issues but showed less of an impact on completeness and plausibility checks. This is the first study to apply the DQD on multiple, disparate databases across a network. While study-specific checks should still be run, we recommend that all data holders converting their data to the OMOP CDM use the DQD as it ensures conformance to the model specifications and that a database meets a baseline level of completeness and plausibility for use in research.</p

vHOG, a multispecies vertebrate ontology of homologous organs groups

Motivation: Most anatomical ontologies are species-specific, whereas a framework for comparative studies is needed. We describe the vertebrate Homologous Organs Groups ontology, vHOG, used to compare expression patterns between species

From Surveillance to Witnessing: Revanche, Red Road, and the Anti-Revenge Film

This essay examines recent European art films that reinterpret the revenge plot and radically challenge the possibility of legitimized violence. I argue that what I term “anti-revenge” films, in particular Andrea Arnold’s Red Road (2006), and Götz Spielmann’s Revanche (2008), frustrate the desire for vengeance (both the protagonist’s and the spectator’s), replacing violent spectacle with uneasy engagement that inhibits revenge, gesturing instead toward the possibility, however remote, of forgiveness. In both films prolonged surveillance, surveillance ostensibly in the service of retribution, inadvertently becomes a means for ethical engagement that actually prohibits violence. In their failure to conform to generic conventions and their depiction of the collapse of the retributive drive, these films challenge the moral legitimacy of revenge, substituting uneasy, often inconclusive moments of potential forgiveness for violent spectacle

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

The complex TIE between macrophages and angiogenesis

Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway

A Dual Infection Pseudorabies Virus Conditional Reporter Approach to Identify Projections to Collateralized Neurons in Complex Neural Circuits

Replication and transneuronal transport of pseudorabies virus (PRV) are widely used to define the organization of neural circuits in rodent brain. Here we report a dual infection approach that highlights connections to neurons that collateralize within complex networks. The method combines Cre recombinase (Cre) expression from a PRV recombinant (PRV-267) and Cre-dependent reporter gene expression from a second infecting strain of PRV (PRV-263). PRV-267 expresses both Cre and a monomeric red fluorescent protein (mRFP) fused to viral capsid protein VP26 (VP26-mRFP) that accumulates in infected cell nuclei. PRV-263 carries a Brainbow cassette and expresses a red (dTomato) reporter that fills the cytoplasm. However, in the presence of Cre, the dTomato gene is recombined from the cassette, eliminating expression of the red reporter and liberating expression of either yellow (EYFP) or cyan (mCerulean) cytoplasmic reporters. We conducted proof-of-principle experiments using a well-characterized model in which separate injection of recombinant viruses into the left and right kidneys produces infection of neurons in the renal preautonomic network. Neurons dedicated to one kidney expressed the unique reporters characteristic of PRV-263 (cytoplasmic dTomato) or PRV-267 (nuclear VP26-mRFP). Dual infected neurons expressed VP26-mRFP and the cyan or yellow cytoplasmic reporters activated by Cre-mediated recombination of the Brainbow cassette. Differential expression of cyan or yellow reporters in neurons lacking VP26-mRFP provided a unique marker of neurons synaptically connected to dual infected neurons, a synaptic relationship that cannot be distinguished using other dual infection tracing approaches. These data demonstrate Cre-enabled conditional reporter expression in polysynaptic circuits that permits the identification of collateralized neurons and their presynaptic partners

Functional dissection of the Drosophila Kallmann's syndrome protein DmKal-1

BACKGROUND: Anosmin-1, the protein implicated in the X-linked Kallmann's syndrome, plays a role in axon outgrowth and branching but also in epithelial morphogenesis. The molecular mechanism of its action is, however, widely unknown. Anosmin-1 is an extracellular protein which contains a cysteine-rich region, a whey acidic protein (WAP) domain homologous to some serine protease inhibitors, and four fibronectin-like type III (FnIII) repeats. Drosophila melanogaster Kal-1 (DmKal-1) has the same protein structure with minor differences, the most important of which is the presence of only two FnIII repeats and a C-terminal region showing a low similarity with the third and the fourth human FnIII repeats. We present a structure-function analysis of the different DmKal-1 domains, including a predicted heparan-sulfate binding site. RESULTS: This study was performed overexpressing wild type DmKal-1 and a series of deletion and point mutation proteins in two different tissues: the cephalopharyngeal skeleton of the embryo and the wing disc. The overexpression of DmKal-1 in the cephalopharyngeal skeleton induced dosage-sensitive structural defects, and we used these phenotypes to perform a structure-function dissection of the protein domains. The reproduction of two deletions found in Kallmann's Syndrome patients determined a complete loss of function, whereas point mutations induced only minor alterations in the activity of the protein. Overexpression of the mutant proteins in the wing disc reveals that the functional relevance of the different DmKal-1 domains is dependent on the extracellular context. CONCLUSION: We suggest that the role played by the various protein domains differs in different extracellular contexts. This might explain why the same mutation analyzed in different tissues or in different cell culture lines often gives opposite phenotypes. These analyses also suggest that the FnIII repeats have a main and specific role, while the WAP domain might have only a modulator role, strictly connected to that of the fibronectins

J/ψ\psi suppression in In-In collisions at 158 GeV/nucleon

The NA60 experiment has studied J/$\psi$ production in Indium-Indium collisions at 158 A$\cdot$GeV. In this paper we present an updated set of results obtained with the complete set of available statistics and an improved alignment of the vertex tracker. The centrality dependence of the J/$\psi$ production, obtained with an analysis technique based only on the J/$\psi$ sample, indicates that a suppression beyond that induced by nuclear absorption is present in In-In collisions, setting in at $\sim$80 participant nucleons. A first study of the systematic errors related with this measurement is discussed. We also present preliminary results on the J/$\psi$ azimuthal distributions.Comment: 8 pages, 3 figures, proceedings of Hard Probes 2006 International Conferenc