The accuracy of the report of hepatic steatosis on ultrasonography in patients infected with hepatitis C in a clinical setting: A retrospective observational study

BACKGROUND: Steatosis is occasionally reported during screening ultrasonography in patients with hepatitis C virus (HCV). We conducted a retrospective observational study to assess the factors associated with steatosis on ultrasonography and the relationship between steatosis on ultrasound versus biopsy in patients infected with HCV in a clinical setting. Our hypothesis was ultrasonography would perform poorly for the detection of steatosis outside of the context of a controlled study, primarily due to false-positive results caused by hepatic fibrosis and inflammation. METHODS: A retrospective review of ultrasound reports was conducted on patients infected with HCV in a tertiary care gastroenterology clinic. Reports were reviewed for the specific documentation of the presence of steatosis. Baseline clinical and histologic parameters were recorded, and compared for patients with vs. without steatosis. Multiple logistic regression analysis was performed on these baseline variables. Liver biopsies were reviewed by two pathologists, and graded for steatosis. Steatosis on biopsy was compared to steatosis on ultrasound report, and the performance characteristics of ultrasonography were calculated, using biopsy as the gold standard. RESULTS: Ultrasound reports were available on 164 patients. Patients with steatosis on ultrasound had a higher incidence of the following parameters compared to patients without steatosis: diabetes (12/49 [24%] vs. 7/115 [6%], p < 0.001), fibrosis stage >2 (15/48 [31%] vs. 16/110 [15%], p = 0.02), histologic grade >2 (19/48 [40%] vs. 17/103 [17%], p = 0.002), and ALT (129.5 ± 89.0 IU/L vs. 94.3 ± 87.0 IU/L, p = 0.01). Histologic grade was the only factor independently associated with steatosis with multivariate analysis. When compared to the histologic diagnosis of steatosis (n = 122), ultrasonography had a substantial number of false-positive and false-negative results. In patients with a normal ultrasound, 8/82 (10%) had >30% steatosis on biopsy. Among patients with steatosis reported on ultrasound, only 12/40 (30%) had >30% steatosis on biopsy review. CONCLUSION: Steatosis on ultrasound is associated with markers of inflammation and fibrosis in HCV-infected patients, but does not consistently correlate with steatosis on biopsy outside of the context of a controlled study. Clinicians should be skeptical of the definitive diagnosis of steatosis on hepatic ultrasonography

Exuberant fibroblast activity compromises lung function via ADAMTS4

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. Severe respiratory infections can result in acute respiratory distress syndrome (ARDS)1. There are no effective pharmacological therapies that have been shown to improve outcomes for patients with ARDS. Although the host inflammatory response limits spread of and eventually clears the pathogen, immunopathology is a major contributor to tissue damage and ARDS1,2. Here we demonstrate that respiratory viral infection induces distinct fibroblast activation states, which we term extracellular matrix (ECM)-synthesizing, damage-responsive and interferon-responsive states. We provide evidence that excess activity of damage-responsive lung fibroblasts drives lethal immunopathology during severe influenza virus infection. By producing ECM-remodelling enzymes—in particular the ECM protease ADAMTS4—and inflammatory cytokines, damage-responsive fibroblasts modify the lung microenvironment to promote robust immune cell infiltration at the expense of lung function. In three cohorts of human participants, the levels of ADAMTS4 in the lower respiratory tract were associated with the severity of infection with seasonal or avian influenza virus. A therapeutic agent that targets the ECM protease activity of damage-responsive lung fibroblasts could provide a promising approach to preserving lung function and improving clinical outcomes following severe respiratory infections

Publisher Correction: Exuberant fibroblast activity compromises lung function via ADAMTS4 (Nature, (2020), 587, 7834, (466-471), 10.1038/s41586-020-2877-5)

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. An amendment to this paper has been published and can be accessed via a link at the top of the paper

Understanding the Use of Crisis Informatics Technology among Older Adults

Mass emergencies increasingly pose significant threats to human life, with a disproportionate burden being incurred by older adults. Research has explored how mobile technology can mitigate the effects of mass emergencies. However, less work has examined how mobile technologies support older adults during emergencies, considering their unique needs. To address this research gap, we interviewed 16 older adults who had recent experience with an emergency evacuation to understand the perceived value of using mobile technology during emergencies. We found that there was a lack of awareness and engagement with existing crisis apps. Our findings characterize the ways in which our participants did and did not feel crisis informatics tools address human values, including basic needs and esteem needs. We contribute an understanding of how older adults used mobile technology during emergencies and their perspectives on how well such tools address human values.Comment: 10 page

Uropathogenic Escherichia coli Modulates Immune Responses and Its Curli Fimbriae Interact with the Antimicrobial Peptide LL-37

Bacterial growth in multicellular communities, or biofilms, offers many potential advantages over single-cell growth, including resistance to antimicrobial factors. Here we describe the interaction between the biofilm-promoting components curli fimbriae and cellulose of uropathogenic E. coli and the endogenous antimicrobial defense in the urinary tract. We also demonstrate the impact of this interplay on the pathogenesis of urinary tract infections. Our results suggest that curli and cellulose exhibit differential and complementary functions. Both of these biofilm components were expressed by a high proportion of clinical E. coli isolates. Curli promoted adherence to epithelial cells and resistance against the human antimicrobial peptide LL-37, but also increased the induction of the proinflammatory cytokine IL-8. Cellulose production, on the other hand, reduced immune induction and hence delayed bacterial elimination from the kidneys. Interestingly, LL-37 inhibited curli formation by preventing the polymerization of the major curli subunit, CsgA. Thus, even relatively low concentrations of LL-37 inhibited curli-mediated biofilm formation in vitro. Taken together, our data demonstrate that biofilm components are involved in the pathogenesis of urinary tract infections by E. coli and can be a target of local immune defense mechanisms

Numerical simulations of flow-topography interaction using unstructured grids

Eddies and jets are important components of global ocean momentum and heat budgets but are typically unresolved in low resolution global climate models. Herein, they are evaluated with an idealised model set–up that incorporates barotropic flow, past a cylinder on a β –plane. The flow dynamics are a function of two non–dimensional numbers: the Reynolds number and the [Symbol appears here. To view, please open pdf attachment] –parameter. The model used, Fluidity–ICOM, utilises unstructured meshes and a new stable mixed discontinuous/continuous finite element pair (P1DGP2). Unstructured meshes decrease the computational cost; the simulations using a non–uniform unstructured mesh had approximately 40% fewer nodes and ran at twice the speed of a uniform structured mesh for a comparable drag coefficient (Cd). The validation of Fluidity–ICOM was performed for a range of Reynolds numbers (0:0 < Re [Mathematical symbol appears here. To view, please open pdf attachment] 3 x 10[to the power of six]) and the percentage difference between published and Fluidity–ICOM values of Cd was found to be less than 10% for the regimes where the dynamics are essentially two–dimensional. The validation highlighted two important considerations: the position of the lateral domain boundary and the boundary mesh resolution. The wake structure for a moderate Reynolds number (1000) and [Symbol appears here. To view, please open pdf attachment] –parameter (75) changed significantly between coarse and fine boundary resolutions. The former was comprised of a double jet structure and the latter a single jet in the lee of the cylinder. This study demonstrated that resolving the frictional boundary layer dynamics is crucially important, as they substantially impact on the downstream flow. Evaluation of the single jet structure for a large parameter space [Mathematical formula appears here. To view, please open pdf attachment] revealed the presence of interfacial Rossby waves with both eastward and westward propagation with respect to the mean flow. The Rossby wave occurred due to the presence of a strong staircase gradient in absolute vorticity. As the Reynolds number increased for a fixed [Symbol appears here. To view, please open pdf attachment] –parameter, the presence of a stronger shear resulted in a faster phase speed of the Rossby wave and a stronger mean–flow. This parameter–space also showed a large dependence on drag to the [Symbol appears here. To view, please open pdf attachment] –parameter. Overall, this study has implications for the Gulf Stream separation and for understanding the interaction of the Antarctic Circumpolar Current (ACC) with topography.EThOS - Electronic Theses Online ServiceGBUnited Kingdo