Objective. To examine the role of interferon regulatory factor 3 (IRF-3) in the regulation of interleukin-23 (IL-23) production in patients with systemic lupus erythematosus (SLE).Methods. Bone marrow-derived macrophages were isolated from both wild-type and IRF3 Ϫ/Ϫ C57BL/6 mice. These cells were stimulated with the Toll-like receptor 3 (TLR-3) agonist poly(I-C), and IL-23p19 cytokine levels were analyzed by enzyme-linked immunosorbent assay. IRF-3 binding to the IL-23p19 gene promoter region in monocytes from patients with SLE and healthy control subjects was analyzed by chromatin immunoprecipitation (ChIP) assay. Luciferase reporter gene assays were performed to identify key drivers of IL-23p19 promoter activity. TANK-binding kinase 1 (TBK-1) protein levels were determined by Western blotting.Results. ChIP assays demonstrated that IRF-3 was stably bound to the human IL-23p19 promoter in monocytes; this association increased following TLR-3 stimulation. Patients with SLE demonstrated increased levels of IRF-3 bound to the IL-23p19 promoter compared with control subjects, which correlated with enhanced IL-23p19 production in monocytes from patients with SLE. Investigations of the TLR-3-driven responses in monocytes from patients with SLE revealed that TBK-1, which is critical for regulating IRF-3 activity, was hyperactivated in both resting and TLR-3-stimulated cells.Conclusion. Our results demonstrate for the first time that patients with SLE display enhanced IL-23p19 expression as a result of hyperactivation of TBK-1, resulting in increased binding of IRF-3 to the promoter. These findings provide novel insights into the molecular pathogenesis of SLE and the potential role for TLR-3 in driving this response.Interleukin-23 (IL-23) is a novel member of the IL-12 family of cytokines and is expressed predominantly by monocytes, macrophages, and dendritic cells in response to stimulation by a variety of Toll-like receptors (TLRs). This cytokine plays a pivotal role in both immunity against pathogens and autoimmunity against self (1). IL-23 is a heterodimeric cytokine composed of a unique p19 subunit and a p40 subunit that is shared with IL-12, held together by an interchain disulfide bond. Although IL-12 and IL-23 share the p40 subunit, the activity of each cytokine is unique (2), with IL-12 promoting the development of interferon-␥ (IFN␥)-producing Th1 cells (3) and IL-23 promoting the expansion of a novel subset of CD4ϩ effector T cells known as Th17 cells (4-6).
Introduction and aimsConcerns had been raised at clinical governance regarding the safety of our inpatient ward rounds with particular reference to: documentation of clinical observations and National Early Warning Score (NEWS), compliance with Trust guidance for venous thromboembolism (VTE) risk assessment, antibiotic stewardship, palliative care and treatment escalation plans (TEP). This quality improvement project was conceived to ensure these parameters were considered and documented during the ward round, thereby improving patient care and safety. These parameters were based on Trust patient safety guidance and CQUIN targets.MethodThe quality improvement technique of plan–do–study–act (PDSA) was used in this project. We retrospectively reviewed ward round entries to record baseline measurements, based on the above described parameters, prior to making any changes. Following this, the change applied was the introduction of a ward round template to include the highlighted important baseline parameters. Monthly PDSA cycles are performed, and baseline measurements are re-examined, then relevant changes were made to the ward round template.Summary of resultsDocumentation of baseline measurements was poor prior to introduction of the ward round template; this improved significantly following introduction of a standardised ward round template. Following three cycles, documentation of VTE risk assessments increased from 14% to 92%. Antibiotic stewardship documentation went from 0% to 100%. Use of the TEP form went from 29% to 78%.ConclusionsFollowing introduction of the ward round template, compliance improved significantly in all safety parameters. Important safety measures being discussed on ward rounds will lead to enhanced patient safety and will improve compliance to Trust guidance and comissioning for quality and innovation (CQUIN) targets. Ongoing change implementation will focus on improving compliance with usage of the template on all urology ward rounds.
As modern business and financial institutions have come to rely more and more on large scale computers for management support, the magnitude of the risks and their potential consequences has increased correspondingly. In addition, large systems involving multiprocessing, resource sharing, and distributed processing have given rise to a new generation of risks due to the increased vulnerabilities of such large scale systems and the potential for fraudulent or malicious misuse of their resources. Somehow, these risks must be managed since either deliberate or accidental impairment of these large scale systems can have serious consequences for the business. That is, threats must be identified, and the likelihood of their occurrences and the elements of the system vulnerable to each of these threats must be established. Any program for risk management must begin with a risk analysis to compare the vulnerabilities in order to pinpoint and rank the system's weaknesses and to provide a guide for the cost-effective, systematic reduction of the probability of the system's being subverted or otherwise impaired.
The computer has unleashed countless opportunities fo r industrial growth, activity, new applications, labor-savin g accomplishments, improving the quality of decisions an d many others . At the same time, computer technology ha s spawned a whole new field of crime and generated a series of problems for both designers and users of information systems . A perusal of some of the better publicized horror stories will attest to this situation [43] .In the middle 1960's there arose in Congress discussion s over the issues of privacy and the computer . A nationa l data bank had been proposed and the public testimony t o Congressional committees and others fills a number o f books [161,222] . At that time the general consensus wa s that technology had not advanced to the point where an y semblance of privacy could be insured [121] .As systems became more complex and sophisticated, s o did the problems of data integrity . Resource-sharing systems achieve their greatest advantage when used simultaneously by many customers . This also means simultaneou s processing of data with varying needs for privacy .As the flexibility and capability of systems improve, th e need for and the complexity of security controls threaten s to grow at a faster rate . With many users on line at on e time, system crashes become more serious and the entir e operation becomes more complex, therefore subject to error . Finally, with the integration of data bases and the advent of data base management systems, the need fo r privacy becomes acute [27] . Organizational boundarie s still exist ; nevertheless, it takes a secure system to convince users to share their data with competitors, whethe r they are in another organization or the same . This paper will attempt to survey the technical aspect s of data security . The scope and complexity of the field becomes apparent when a survey of the literature turns u p hundreds of articles dealing with physical security ; threat s to the computer ; protection against fraud, embezzlement , and other human failings ; the need for insurance ; software protection ; hardware safeguards ; legal aspects ; ris k management; auditing ; computer system design ; and th e PETER S . BROWNE received his MBA from the University of Nebraska at Omaha in May, 1971 . He has served in various programmin g and analyst positions for the Strategic Air Command, culminatin g his military career as Project Manager for the design of a multilevel security package implemented on the World Wide Militar y Command and Control System at SAC . He was a Committee Chairman for SIGFIDET, is its present secretary-treasurer, and was th e Chairman of the ACM Midlands Chapter at Omaha, Nebraska . Other activities include his participation as a working member o f the GUIDE/SHARE Data Base Task Group and instructorship at th e University of Nebraska at Omaha . He gave the platform presentation at the SIGBDP meeting in Boston in August, 1972 . Presentl y Computer Security Manager at State Farm Insurance Company, h e is in the process of implement...
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