3,340 research outputs found

    Reaching Approximate Byzantine Consensus with Multi-hop Communication

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    We address the problem of reaching consensus in the presence of Byzantine faults. In particular, we are interested in investigating the impact of messages relay on the network connectivity for a correct iterative approximate Byzantine consensus algorithm to exist. The network is modeled by a simple directed graph. We assume a node can send messages to another node that is up to ll hops away via forwarding by the intermediate nodes on the routes, where l∈Nl\in \mathbb{N} is a natural number. We characterize the necessary and sufficient topological conditions on the network structure. The tight conditions we found are consistent with the tight conditions identified for l=1l=1, where only local communication is allowed, and are strictly weaker for l>1l>1. Let l∗l^* denote the length of a longest path in the given network. For l≥l∗l\ge l^* and undirected graphs, our conditions hold if and only if n≥3f+1n\ge 3f+1 and the node-connectivity of the given graph is at least 2f+12f+1 , where nn is the total number of nodes and ff is the maximal number of Byzantine nodes; and for l≥l∗l\ge l^* and directed graphs, our conditions is equivalent to the tight condition found for exact Byzantine consensus. Our sufficiency is shown by constructing a correct algorithm, wherein the trim function is constructed based on investigating a newly introduced minimal messages cover property. The trim function proposed also works over multi-graphs.Comment: 24 pages, 1 figure. arXiv admin note: text overlap with arXiv:1203.188

    Genetic structure of community acquired methicillin-resistant Staphylococcus aureus USA300.

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    BackgroundCommunity-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a significant bacterial pathogen that poses considerable clinical and public health challenges. The majority of the CA-MRSA disease burden consists of skin and soft tissue infections (SSTI) not associated with significant morbidity; however, CA-MRSA also causes severe, invasive infections resulting in significant morbidity and mortality. The broad range of disease severity may be influenced by bacterial genetic variation.ResultsWe sequenced the complete genomes of 36 CA-MRSA clinical isolates from the predominant North American community acquired clonal type USA300 (18 SSTI and 18 severe infection-associated isolates). While all 36 isolates shared remarkable genetic similarity, we found greater overall time-dependent sequence diversity among SSTI isolates. In addition, pathway analysis of non-synonymous variations revealed increased sequence diversity in the putative virulence genes of SSTI isolates.ConclusionsHere we report the first whole genome survey of diverse clinical isolates of the USA300 lineage and describe the evolution of the pathogen over time within a defined geographic area. The results demonstrate the close relatedness of clinically independent CA-MRSA isolates, which carry implications for understanding CA-MRSA epidemiology and combating its spread

    Augmenting Endogenous Levels of Retinal Annexin A1 Suppresses Uveitis in Mice

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    PURPOSE: The purpose of this study was to examine the expression of the anti-inflammatory protein Annexin A1 (AnxA1) in mice and human retinae during uveitis and to determine whether local administration of human recombinant AnxA1 (hrAnxA1) can suppress uveitis in mice. METHODS: Retinal sections from mice (healthy normal and uveitis) and postmortem human (no history of eye disease (n = 5) and uveitis (n = 7)) were stained for AnxA1 expression and imaged by immunofluorescence microscopy. AnxA1 cellular expression was determined by colabeling with CD45, glial fibrillary acidic protein (GFAP), and Iba-1 cells, with additional staining of AnxA1 receptors formyl peptide receptor 1 (FPR1) and FPRL1/FPR2. Mice with acute endotoxin-induced uveitis and chronic experimental autoimmune uveitis were treated locally by intravitreal injection with hrAnxA1, and disease was assessed by clinical scoring and quantification of leukocyte infiltrate via flow cytometry. RESULTS: Constitutive expression of AnxA1 was observed in both healthy mouse and human retinae, and its expression increased during uveitis compared to healthy controls. AnxA1 colocalizes predominantly with CD45(+) cells, GFAP(+) macroglia, and to a lesser extent, Iba-1(+) myeloid cells. We also demonstrate that local treatment with hrAnxA1 attenuates the severity of uveitis in mice. CONCLUSIONS: These data indicate that locally expressed AnxA1 is elevated in the retina during intraocular inflammation. We demonstrate that local administration of hrAnxA1 to augment levels results in suppression of uveitis in mice. TRANSLATIONAL RELEVANCE: Our data suggest that elevated expression of retinal AnxA1 in human uveitis may be immunoregulatory and that local supplementation with hrAnxA1 may provide a potential novel treatment for inflammatory eye diseases such as noninfectious uveitis

    Assessment and in vivo scoring of murine experimental autoimmune uveoretinitis using optical coherence tomography

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    Despite advances in clinical imaging and grading our understanding of retinal immune responses and their morphological correlates in experimental autoimmune uveoretinitis (EAU), has been hindered by the requirement for post-mortem histology. To date, monitoring changes occurring during EAU disease progression and evaluating the effect of therapeutic intervention in real time has not been possible. We wanted to establish whether optical coherence tomography (OCT) could detect intraretinal changes during inflammation and to determine its utility as a tool for accurate scoring of EAU. EAU was induced in C57BL/6J mice and animals evaluated after 15, 26, 36 and 60 days. At each time-point, contemporaneous Spectralis-OCT scanning, topical endoscopic fundal imaging (TEFI), fundus fluorescein angiography (FFA) and CD45-immunolabelled histology were performed. OCT features were further characterised on retinal flat-mounts using immunohistochemistry and 3D reconstruction. Optic disc swelling and vitreous opacities detected by OCT corresponded to CD45+ cell infiltration on histology. Vasculitis identified by FFA and OCT matched perivascular myeloid and T-cell infiltrates and could be differentiated from unaffected vessels. Evolution of these changes could be followed over time in the same eye. Retinal folds were visible and found to encapsulate mixed populations of activated myeloid cells, T-cells and microglia. Using these features, an OCT-based EAU scoring system was developed, with significant correlation to validated histological (Pearson r(2) = 0.6392, P<0.0001, n = 31 eyes) and TEFI based scoring systems (r(2) = 0.6784, P<0.0001). OCT distinguishes the fundamental features of murine EAU in vivo, permits dynamic assessment of intraretinal changes and can be used to score disease severity. As a result, it allows tissue synchronisation with subsequent cellular and functional assessment and greater efficiency of animal usage. By relating OCT signals with immunohistochemistry in EAU, our findings offer the opportunity to inform the interpretation of OCT changes in human uveitis

    Diabetes mellitus in Addis Ababa, Ethiopia: admissions, complications and outcomes in a large referral hospital.

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    SETTING: The Black Lion Referral Hospital, Addis Ababa, Ethiopia. OBJECTIVE: To document indications for admission, complications and outcomes of patients with diabetes mellitus (DM) admitted between 2010 and 2013. DESIGN: A descriptive retrospective study using medical files. RESULTS: Of 8048 admissions, 523 (6.5%) had DM; of these, 418 medical records were retrieved: 301 (72%) patients had type 2 and 104 (28%) type 1 disease, with male sex (62%) and older age (median age 60 years) being features of type 2 disease. Main admission diagnoses for type 2 disease were diabetic foot ulcer (39%) and cardiovascular disease (21%); for type 1 disease, it was diabetic ketoacidosis (62%). Hypertension, neuropathy, nephropathy, retinopathy and diabetic foot accounted for 85% of the 756 existing complications. Overall in-patient mortality was 21%. Of the 89 deaths, 77 occurred among patients with type 2 disease; the main indications for admission were diabetic foot ulcer/gangrene and cardiovascular disease. CONCLUSION: DM, especially type 2 DM, is an important cause of admission to Ethiopia's largest referral hospital. Many patients had already developed disease-related complications at admission, and mortality was high. There is a need to improve awareness about and care for DM in Ethiopia

    Generalized Uncertainty Principle, Modified Dispersion Relation and Barrier penetration by a Dirac particle

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    We have studied the energy band structure of a Dirac particle in presence of a generalised uncertainty principle (GUP). We start from defining a modified momentum operator and derive corresponding modified dispersion relation (MDR) and GUP. Apart from the forbidden band within the range ±m\pm m, mm being the mass of the particle, we find the existence of additional forbidden bands at the both ends of the spectrum. Such band structure forbids a Dirac particle to penetrate a potential step of sufficient height (∼EP\sim E_P, EPE_P being Planck energy). This is also true for massless particle. Unlike the relativistic case, a massless particle also can reflect from a barrier of sufficient height. Finally we discuss about the Klein's paradox in presence of the GUP.Comment: 10 pages, 7 figures, LaTe

    Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model

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    Endotoxin-induced uveitis (EIU) in rodents is a model of acute Toll-like receptor 4 (TLR4)-mediated organ inflammation, and has been used to model human anterior uveitis, examine leukocyte trafficking and test novel anti-inflammatory therapeutics. Wider adoption has been limited by the requirement for manual, non-specific, cell-count scoring of histological sections from each eye as a measure of disease severity. Here, we describe a comprehensive and efficient technique that uses ocular dissection and multimodal tissue analysis. This allows matched disease scoring by multicolour flow cytometric analysis of the inflammatory infiltrate, protein analysis on ocular supernatants and qPCR on remnant tissues of the same eye. Dynamic changes in cell populations could be identified and mapped to chemokine and cytokine changes over the course of the model. To validate the technique, dose-responsive suppression of leukocyte infiltration by recombinant interleukin-10 was demonstrated, as well as selective suppression of the monocyte (CD11b+Ly6C+) infiltrate, in mice deficient for eitherCcl2orCcr2 Optical coherence tomography (OCT) was used for the first time in this model to allowin vivoimaging of infiltrating vitreous cells, and correlated with CD11b+Ly6G+ counts to provide another unique measure of cell populations in the ocular tissue. Multimodal tissue analysis of EIU is proposed as a new standard to improve and broaden the application of this model

    PREVALENCE AND RISK FACTORS ASSOCIATED WITH VULVOVAGINAL CANDIDIASIS DURING PREGNANCY IN SANA'A, YEMEN

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    Background and objective: Women at pregnancy are further susceptible to vaginal colonization and yeast infection. The responsibility of Candida colonization in the incidence of preterm birth is correctly established. Knowing regional epidemiology and identifying risk factors of preterm birth are important for management and preventive strategies. The aim of the study was to reveal the prevalence of Candida species in vaginal swabs of pregnant women and determine odds ratio of risks for vulvovaginal candidiasis (VVC). Methods:   Pregnant women attendance routine antenatal visits in Al-Olify –family Center in Sana'a city were registered into a cross-sectional study carried out from June 2018 to March 2019. The laboratory works were carried out in the National Center of Public Laboratories (NCPHL). Samples of vaginal swabs were taken from contributors after obtaining oral consent. The classification of the Candida species was done by culture on HiCrome Candida Differential Agar at 35 °C for 48 h for making of species-specific colors. Data of demographic, clinical and risk factors were collected in a pre-designed questionnaire. Results: A total of 190 pregnant women are included. The rate of VVC was 51.6%. Candida albicans accounted for 39.5% and non-Candida albicans accounted for 12.1% of isolates, mainly C. glabrata (4.7%), C. lipolytica (3.2%), and C. famata (2.1%). When VVC risk factors were considered, there were significant risk factors with the age group 20-24 years (61%, odds ratio (OR) = 1.8), first trimester of pregnancy (61.1%, OR = 1.7), Multipara of  parity (61.8%, OR = 1.9), low socioeconomic level (60.1%, OR =2.4), and illiteracy (68%, OR = 2.2). When clinical symptoms were considered, only 86.2% of affected females had clinical signs of VVC. Conclusions: There is a high probable rate of VVC is found among pregnant women in Yemen, undiagnosed and unnoticed; and this highlights the need for health authorities to develop strategies for diagnosing VVC, including vaginal swabs for candidiasis as a routine procedure for all pregnant women. This study also revealed a steady increase in time with a non-C. albicans species  prevalence rate. VVC syndrome management guidelines in Yemen should be revised to include a special protocol for pregnant women.                                       Peer Review History: Received 14 May 2020; Revised 15 June; Accepted 1 July, Available online 15 July 2020 Academic Editor: Dr. Muhammad Zahid Iqbal, AIMST University, Malaysia, [email protected] Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Dr. Michael Otakhor Erhunmwunse, BTU – Cottbus, Germany, [email protected]  Dr. Mohamed Awad Mousnad,  Faculty of Pharmacy, International University of Africa (IUA), Khartoum, Sudan, [email protected]  Similar Articles: TETANUS IMMUNIZATION AMONG PREGNANT WOMEN: COVERAGE RATE AND RATE OF PROTECTION AT TIME OF DELIVERY AN EXHAUSTIVE STATISTIC ON CURRENT MUCOADHESIVE INTRAVAGINAL DRUG DELIVERY METHODOLOGIE

    High-levelexpression of functional recombinant human coagulation factor VII in insect cells

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    Abstract: Recombinant coagulation factor VII (FVII) is used as a potential therapeutic intervention in hemophilia patients who produce antibodies against the coagulation factors. Mammalian cell lines provide low levels of expression, however, the Spodoptera frugiperda Sf9 cell line and baculovirus expression system are powerful systems for high-level expression of recombinant proteins, but due to the lack of endogenous vitamin K-dependent carboxylase, expression of functional FVII using this system is impossible. In the present study, we report a simple but versatile method to overcome the defect for high-level expression of the functional recombinant coagulation FVII in Sf9 cells. This method involves simultaneous expression of both human γ-carboxylase (hGC) and human FVII genes in the host. It may be possible to express other vitamin K-dependent coagulation factors using this method in the future. Keywords: Baculovirus; γ-carboxylase; Coagulation FVII; Factor VII; Insect cel

    Countrywide roll-out of Xpert(®) MTB/RIF in Swaziland: the first three years of implementation.

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    SETTING: All 19 public health laboratories in Swaziland that had Xpert(®) MTB/RIF machines installed as part of a countrywide roll-out between June 2011 and June 2014. OBJECTIVE: To evaluate the utilisation and functionality of Xpert from 2011 to mid-2014. DESIGN: Descriptive study of Xpert implementation using routinely collected data. RESULTS: Of 48 829 Xpert tests conducted, 93% were successful: 14% detected Mycobacterium tuberculosis and 12% showed rifampicin resistance. The most common cause of unsuccessful tests was an 'Error' result (62%). Similar findings were obtained in government-supported and partner-supported laboratories. Annual utilisation of Xpert improved from 51% of maximum capacity in 2011 and 2012 to 74% in 2013 and 2014. A monitoring and supervision exercise of all Xpert testing sites in 2014 showed a generally good performance, with over 50% of laboratories achieving a ⩾80% score on most components. However, poor scores were obtained with equipment use and maintenance (6% achieving a score of ⩾80%), internal audit (19% achieving a score of ⩾80%) and process control (25% achieving a score of ⩾80%). CONCLUSION: Countrywide roll-out of Xpert in Swaziland has been successful, although operational issues have been identified and need to be resolved
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