Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review

Background: The 2013-15 Ebola outbreak was unprecedented due to sustainedtransmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Methods: Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. [1] Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. Results: 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Conclusions: Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood

Probabilistic Model-Based Safety Analysis

Model-based safety analysis approaches aim at finding critical failure combinations by analysis of models of the whole system (i.e. software, hardware, failure modes and environment). The advantage of these methods compared to traditional approaches is that the analysis of the whole system gives more precise results. Only few model-based approaches have been applied to answer quantitative questions in safety analysis, often limited to analysis of specific failure propagation models, limited types of failure modes or without system dynamics and behavior, as direct quantitative analysis is uses large amounts of computing resources. New achievements in the domain of (probabilistic) model-checking now allow for overcoming this problem. This paper shows how functional models based on synchronous parallel semantics, which can be used for system design, implementation and qualitative safety analysis, can be directly re-used for (model-based) quantitative safety analysis. Accurate modeling of different types of probabilistic failure occurrence is shown as well as accurate interpretation of the results of the analysis. This allows for reliable and expressive assessment of the safety of a system in early design stages

ISAAC, a framework for integrated safety analysis of functional, geometrical and human aspects

International audienceThis paper aims at presenting methods and tools that are developed in the ISAAC project (Improvement of Safety Activities on Aeronautical Complex Systems, www.isaac-fp6.org), a European Community funded project, to support the safety assessment of complex embedded systems. The ISAAC methodology proposes to base as much of the safety analyses as is feasibly possible on simulable and formally verifiable system models that include fault models and can be shared both by safety and design engineers. On one hand, tools were developed to support safety assessment of Simulink, SCADE, Statemate, NuSMV and AltaRica models. On the other hand, formal models are coupled with additional models to address the problems of common cause analysis and human error analysis

Ablation of integrin-mediated cell-collagen communication alleviates fibrosis

Objectives Activation of fibroblasts is a hallmark of fibrotic processes. Besides cytokines and growth factors, fibroblasts are regulated by the extracellular matrix environment through receptors such as integrins, which transduce biochemical and mechanical signals enabling cells to mount appropriate responses according to biological demands. The aim of this work was to investigate the in vivo role of collagen–fibroblast interactions for regulating fibroblast functions and fibrosis. Methods Triple knockout (tKO) mice with a combined ablation of integrins α1β1, α2β1 and α11β1 were created to address the significance of integrin-mediated cell–collagen communication. Properties of primary dermal fibroblasts lacking collagen-binding integrins were delineated in vitro. Response of the tKO mice skin to bleomycin induced fibrotic challenge was assessed. Results Triple integrin-deficient mice develop normally, are transiently smaller and reveal mild alterations in mechanoresilience of the skin. Fibroblasts from these mice in culture show defects in cytoskeletal architecture, traction stress generation, matrix production and organisation. Ablation of the three integrins leads to increased levels of discoidin domain receptor 2, an alternative receptor recognising collagens in vivo and in vitro. However, this overexpression fails to compensate adhesion and spreading defects on collagen substrates in vitro. Mice lacking collagen-binding integrins show a severely attenuated fibrotic response with impaired mechanotransduction, reduced collagen production and matrix organisation. Conclusions The data provide evidence for a crucial role of collagen-binding integrins in fibroblast force generation and differentiation in vitro and for matrix deposition and tissue remodelling in vivo. Targeting fibroblast–collagen interactions might represent a promising therapeutic approach to regulate connective tissue deposition in fibrotic diseases

Condition-Dependent Cell Volume and Concentration of Escherichia coli to Facilitate Data Conversion for Systems Biology Modeling

Systems biology modeling typically requires quantitative experimental data such as intracellular concentrations or copy numbers per cell. In order to convert population-averaging omics measurement data to intracellular concentrations or cellular copy numbers, the total cell volume and number of cells in a sample need to be known. Unfortunately, even for the often studied model bacterium Escherichia coli this information is hardly available and furthermore, certain measures (e.g. cell volume) are also dependent on the growth condition. In this work, we have determined these basic data for E. coli cells when grown in 22 different conditions so that respective data conversions can be done correctly. First, we determine growth-rate dependent cell volumes. Second, we show that in a 1 ml E. coli sample at an optical density (600 nm) of 1 the total cell volume is around 3.6 µl for all conditions tested. Third, we demonstrate that the cell number in a sample can be determined on the basis of the sample's optical density and the cells' growth rate. The data presented will allow for conversion of E. coli measurement data normalized to optical density into volumetric cellular concentrations and copy numbers per cell - two important parameters for systems biology model development

Genetic Discrimination Between LADA and Childhood-Onset Type 1 Diabetes Within the MHC

OBJECTIVE The MHC region harbors the strongest loci for latent autoimmune diabetes in adults (LADA); however, the strength of association is likely attenuated compared with that for childhood-onset type 1 diabetes. In this study, we recapitulate independent effects in the MHC class I region in a population with type 1 diabetes and then determine whether such conditioning in LADA yields potential genetic discriminators between the two subtypes within this region. RESEARCH DESIGN AND METHODS Chromosome 6 was imputed using SNP2HLA, with conditional analysis performed in type 1 diabetes case subjects (n = 1,985) and control subjects (n = 2,219). The same approach was applied to a LADA cohort (n = 1,428) using population-based control subjects (n = 2,850) and in a separate replication cohort (656 type 1 diabetes case, 823 LADA case, and 3,218 control subjects). RESULTS The strongest associations in the MHC class II region (rs3957146, beta [SE] = 1.44 [0.05]), as well as the independent effect of MHC class I genes, on type 1 diabetes risk, particularly HLA-B*39 (beta [SE] = 1.36 [0.17]), were confirmed. The conditional analysis in LADA versus control subjects showed significant association in the MHC class II region (rs3957146, beta [SE] = 1.14 [0.06]); however, we did not observe significant independent effects of MHC class I alleles in LADA. CONCLUSIONS In LADA, the independent effects of MHC class I observed in type 1 diabetes were not observed after conditioning on the leading MHC class II associations, suggesting that the MHC class I association may be a genetic discriminator between LADA and childhood-onset type 1 diabetes.Peer reviewe

Anatomical classification of the shape and topography of the stomach

The aim of the study was to present the classification of anatomical variations of the stomach, based on the radiological and historical data. In years 2006–2010, 2,034 examinations of the upper digestive tract were performed. Normal stomach anatomy or different variations of the organ shape and/or topography without any organic radiologically detectable gastric lesions were revealed in 568 and 821 cases, respectively. Five primary groups were established: abnormal position along longitudinal (I) and horizontal axis (II), as well as abnormal shape (III) and stomach connections (IV) or mixed forms (V). The first group contains abnormalities most commonly observed among examined patients such as stomach rotation and translocation to the chest cavity, including sliding, paraesophageal, mixed-form and upside-down hiatal diaphragmatic hernias, as well as short esophagus, and the other diaphragmatic hernias, that were not found in the evaluated population. The second group includes the stomach cascade. The third and fourth groups comprise developmental variations and organ malformations that were not observed in evaluated patients. The last group (V) encloses mixed forms that connect two or more previous variations

Clostridium difficile isolates with increased sporulation: emergence of PCR ribotype 002 in Hong Kong

We identified a predominant clone of Clostridium difficile PCR ribotype 002, which was associated with an increased sporulation frequency. In 2009, 3,528 stool samples from 2,440 patients were tested for toxigenic C. difficile in a healthcare region in Hong Kong. A total of 345 toxigenic strains from 307 (13.3%) patients were found. Ribotype 002 was the predominant ribotype, which constituted 35 samples from 29 (9.4%) patients. The mean sporulation frequency of ribotype 002 was 20.2%, which was significantly higher than that of the 56 randomly selected ribotypes other than 002 as concurrent controls (3.7%, p < 0.001). Patients carrying toxigenic ribotype 002 were more frequently admitted from an elderly home (p = 0.01) and received more β-lactam antibiotics in the preceding 3 months compared with the controls (p = 0.04) . The identification of toxigenic ribotype 002 in 2009 was temporally related to a significant increase in both the incidence of toxigenic C. difficile from 0.53 to 0.95 per 1,000 admissions (p < 0.001) and the rate of positive detection from 4.17% to 6.28% (p < 0.001) between period 1 (2004–2008) and period 2 (2009). This finding should alert both the physician and the infection control team to the establishment of and possible outbreaks by ribotype 002 in our hospitals, as in the case of ribotype 027