Main clinical manifestations of a bleeding diathesis: an often disregarded aspect of medical and surgical history taking

Summary.  A suitable clinical evaluation of a bleeding diathesis is often forgone. The young doctor is often unprepared to describe in an accurate way the different types of bleeding. An adequate classification and adequate clinical information about a bleeding diathesis are instead of paramount importance. Bleeding may be cutaneous, mucous, articular, muscular, parenchymal, intracavitary, orificial. Each of these sites and forms may have diagnostic implications. An accurate description of the several forms of cutaneous bleeding (petechiae, purpuric spots, ecchymosis, haematomas, etc.) is needed for referrals and for controls. The correct evaluation of cutaneous bleeding manifestations of children (battered child syndrome) is absolutely important for clinical and medico‐legal purposes. The same is true for the battering syndrome seen in women abused by their spouses. The grading of haemarthrosis in haemophilia patients is important for the follow‐up. A proper description of haematuria is essential in suggesting the probable site of bleeding (kidney or bladder or urethra). A proper evaluation of bleeding may give also useful information on the general health status of the patients (presence of anaemia, poor nutrition, renal insufficiency, etc.). The combination of bleeding and thrombosis in the same patient is also a clinical challenge. The relationship between haemorrhage and thrombosis may be sequential or concomitant. Sequential thrombosis may occur in a patient confined in bed for a brain haemorrhage. Concomitant thrombosis and bleeding occur in DIC and in patients with thrombosis being treated with anticoagulants. Finally, it should be kept in mind that a proper evaluation of the bleeding diathesis of a given patient may help the caring doctor in ordering appropriate laboratory tests (e.g. a platelet count for petechiae, a PTT for a patient with haemarthrosis, etc.)

Digitizing mass spectrometry data to explore the chemical diversity and distribution of marine cyanobacteria and algae.

Natural product screening programs have uncovered molecules from diverse natural sources with various biological activities and unique structures. However, much is yet underexplored and additional information is hidden in these exceptional collections. We applied untargeted mass spectrometry approaches to capture the chemical space and dispersal patterns of metabolites from an in-house library of marine cyanobacterial and algal collections. Remarkably, 86% of the metabolomics signals detected were not found in other available datasets of similar nature, supporting the hypothesis that marine cyanobacteria and algae possess distinctive metabolomes. The data were plotted onto a world map representing eight major sampling sites, and revealed potential geographic locations with high chemical diversity. We demonstrate the use of these inventories as a tool to explore the diversity and distribution of natural products. Finally, we utilized this tool to guide the isolation of a new cyclic lipopeptide, yuvalamide A, from a marine cyanobacterium

Invariant manifolds and equilibrium states for non-uniformly hyperbolic horseshoes

In this paper we consider horseshoes containing an orbit of homoclinic tangency accumulated by periodic points. We prove a version of the Invariant Manifolds Theorem, construct finite Markov partitions and use them to prove the existence and uniqueness of equilibrium states associated to H\"older continuous potentials.Comment: 33 pages, 6 figure

Genetic predisposition to hemophagocytic lymphohistiocytosis: report on 500 patients from the Italian registry

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease affecting mostly children but also adults and characterized by hyperinflammatory features. A subset of patients, referred to as having familial hemophagocytic lymphohistiocytosis (FHL), have various underlying genetic abnormalities, the frequencies of which have not been systematically determined previously. Objective This work aims to further our understanding of the pathogenic bases of this rare condition based on an analysis of our 25 years of experience. Methods From our registry, we have analyzed a total of 500 unselected patients with HLH. Results Biallelic pathogenic mutations defining FHL were found in 171 (34%) patients; the proportion of FHL was much higher (64%) in patients given a diagnosis during the first year of life. Taken together, mutations of the genes PRF1 (FHL2) and UNC13D (FHL3) accounted for 70% of cases of FHL. Overall, a genetic diagnosis was possible in more than 90% of our patients with FHL. Perforin expression and the extent of degranulation have been more useful for diagnosing FHL than hemophagocytosis and the cytotoxicity assay. Of 281 (56%) patients classified as having "sporadic" HLH, 43 had monoallelic mutations in one of the FHL-defining genes. Given this gene dosage effect, FHL is not strictly recessive. Conclusion We suggest that the clinical syndrome HLH generally results from the combined effects of an exogenous trigger and genetic predisposition. Within this combination, different weights of exogenous and genetic factors account for the wide disease spectrum that ranges from HLH secondary to severe infection to FHL

Molecular and Microbial Microenvironments in Chronically Diseased Lungs Associated with Cystic Fibrosis.

To visualize the personalized distributions of pathogens and chemical environments, including microbial metabolites, pharmaceuticals, and their metabolic products, within and between human lungs afflicted with cystic fibrosis (CF), we generated three-dimensional (3D) microbiome and metabolome maps of six explanted lungs from three cystic fibrosis patients. These 3D spatial maps revealed that the chemical environments differ between patients and within the lungs of each patient. Although the microbial ecosystems of the patients were defined by the dominant pathogen, their chemical diversity was not. Additionally, the chemical diversity between locales in the lungs of the same individual sometimes exceeded interindividual variation. Thus, the chemistry and microbiome of the explanted lungs appear to be not only personalized but also regiospecific. Previously undescribed analogs of microbial quinolones and antibiotic metabolites were also detected. Furthermore, mapping the chemical and microbial distributions allowed visualization of microbial community interactions, such as increased production of quorum sensing quinolones in locations where Pseudomonas was in contact with Staphylococcus and Granulicatella, consistent with in vitro observations of bacteria isolated from these patients. Visualization of microbe-metabolite associations within a host organ in early-stage CF disease in animal models will help elucidate the complex interplay between the presence of a given microbial structure, antibiotics, metabolism of antibiotics, microbial virulence factors, and host responses.IMPORTANCE Microbial infections are now recognized to be polymicrobial and personalized in nature. Comprehensive analysis and understanding of the factors underlying the polymicrobial and personalized nature of infections remain limited, especially in the context of the host. By visualizing microbiomes and metabolomes of diseased human lungs, we reveal how different the chemical environments are between hosts that are dominated by the same pathogen and how community interactions shape the chemical environment or vice versa. We highlight that three-dimensional organ mapping methods represent hypothesis-building tools that allow us to design mechanistic studies aimed at addressing microbial responses to other microbes, the host, and pharmaceutical drugs

Robust exponential decay of correlations for singular-flows

We construct open sets of Ck (k bigger or equal to 2) vector fields with singularities that have robust exponential decay of correlations with respect to the unique physical measure. In particular we prove that the geometric Lorenz attractor has exponential decay of correlations with respect to the unique physical measure.Comment: Final version accepted for publication with added corrections (not in official published version) after O. Butterley pointed out to the authors that the last estimate in the argument in Subsection 4.2.3 of the previous version is not enough to guarantee the uniform non-integrability condition claimed. We have modified the argument and present it here in the same Subsection. 3 figures, 34 page

Large deviations for non-uniformly expanding maps

We obtain large deviation results for non-uniformly expanding maps with non-flat singularities or criticalities and for partially hyperbolic non-uniformly expanding attracting sets. That is, given a continuous function we consider its space average with respect to a physical measure and compare this with the time averages along orbits of the map, showing that the Lebesgue measure of the set of points whose time averages stay away from the space average decays to zero exponentially fast with the number of iterates involved. As easy by-products we deduce escape rates from subsets of the basins of physical measures for these types of maps. The rates of decay are naturally related to the metric entropy and pressure function of the system with respect to a family of equilibrium states. The corrections added to the published version of this text appear in bold; see last section for a list of changesComment: 36 pages, 1 figure. After many PhD students and colleagues having pointed several errors in the statements and proofs, this is a correction to published article answering those comments. List of main changes in a new last sectio

Creating a 3D microbial and chemical snapshot of a human habitat

Kapono CA, Morton JT, Bouslimani A, et al. Creating a 3D microbial and chemical snapshot of a human habitat. Scientific Reports. 2018;8(1): 3669

Gateways as inter-modal nodes in different ages: The Venetian region, eighteenth to twentieth centuries

This paper focuses on the theoretical implications of a regional case studyfor the analysis of transportation networks and gateway functions. Thestarting point is the result of a research on the changing role of gateways,and on the relocation of the gateway function from one city to a series ofcities in the Venetian region from the eighteenth to the twentieth century.Against this evolution, I test the validity and usefulness of a definition of thegateway as a point of inter-modal exchange for its historical interpretation.Changing transport technologies involve different organisations of inter-modal exchanges, and imply more or less intense economic functions ofgateway cities. These changes intertwine with political events and deci-sions, and more general economic changes: they could at the same time beread as an effect of these transformations, and as a causal factor. From this perspective, a study of intermodality shows to be useful to shed new lighton specific changes in the structure of urban hierarchie