Retinal Pigment Epithelial Cell DNA is Damaged by Exposure to Benzo[a]pyrene, a Constituent of Cigarette Smoke.

This study examined the effect of exogenous benzo[ a ]pyrene (BaP), an important constituent of cigarette smoke, on cultured bovine retinal pigment epithelial (RPE) cells. Evidence is presented for its metabolic conversion into benzo[ a ]pyrene diol epoxide (BPDE) and the consequent formation of potentially cytotoxic nucleobase adducts in DNA. Cultured RPE cells were treated with BaP at concentrations in the range of 0–100 µm. The presence of BaP was found to cause inhibition of cell growth and replication. BaP induced the expression of a phase I drug metabolizing enzyme which was identified as cytochrome P450 1A1 (CYP 1A1) by RT–PCR and by Western blotting. Coincident with the increased expression of CYP 1A1, covalent adducts between the mutagenic metabolite BPDE and DNA could be detected within RPE cells by immunocytochemical staining. Additional support for their formation was afforded by nuclease P1 enhanced 32P-postlabelling assays on cellular DNA. Single-cell gel electrophoresis (comet) assays showed that exposure of RPE cells to BaP rendered them markedly more susceptible to DNA damage induced by broad band UVB or blue light laser irradiation. In the case of UVB, this is consistent with the photosensitization of DNA cleavage by nucleobase adducts of BPDE. Collectively, these findings imply that BaP has a significant impact on RPE cell pathophysiology and suggest mechanisms whereby exposure to cigarette smoke might cause RPE dysfunction and cell death, thus possibly contributing to degenerative disorders of the retina.

Nontypeable Haemophilus influenzae clearance by alveolar macrophages is impaired by exposure to cigarette smoke

Nontypeable Haemophilus influenzae (NTHI) is an opportunistic gram-negative pathogen that causes respiratory infections and is associated with progression of respiratory diseases. Cigarette smoke is a main risk factor for development of respiratory infections and chronic respiratory diseases. Glucocorticoids, which are anti-inflammatory drugs, are still the most common therapy for these diseases. Alveolar macrophages are professional phagocytes that reside in the lung and are responsible for clearing infections by the action of their phagolysosomal machinery and promotion of local inflammation. In this study, we dissected the interaction between NTHI and alveolar macrophages and the effect of cigarette smoke on this interaction. We showed that alveolar macrophages clear NTHI infections by adhesion, phagocytosis, and phagolysosomal processing of the pathogen. Bacterial uptake requires host actin polymerization, the integrity of plasma membrane lipid rafts, and activation of the phosphatidylinositol 3-kinase (PI3K) signaling cascade. Parallel to bacterial clearance, macrophages secrete tumor necrosis factor alpha (TNF-alpha) upon NTHI infection. In contrast, exposure to cigarette smoke extract (CSE) impaired alveolar macrophage phagocytosis, although NTHI-induced TNF-alpha secretion was not abrogated. Mechanistically, our data showed that CSE reduced PI3K signaling activation triggered by NTHI. Treatment of CSE-exposed cells with the glucocorticoid dexamethasone reduced the amount of TNF-alpha secreted upon NTHI infection but did not compensate for CSE-dependent phagocytic impairment. The deleterious effect of cigarette smoke was observed in macrophage cell lines and in human alveolar macrophages obtained from smokers and from patients with chronic obstructive pulmonary disease.

The use of a dynamic truck-trailer drive-by system to monitor bridge damping

Bridge structures are continuously subject to degradation due to the environment, ageing and excess loading. Periodic monitoring of bridges is therefore a key part of any maintenance strategy as it can give early warning if a bridge becomes unsafe. This article investigates an alternative method for the monitoring of bridge dynamic behaviour: a truck-trailer vehicle system, with accelerometers fitted to the axles of the trailer. The method aims to detect changes in the damping of a bridge, which may indicate the existence of damage. A simplified vehicle-bridge interaction model is used in theoretical simulations to assess the effectiveness of the method in detecting those changes. The influence of road profile roughness on the vehicle vibration is overcome by recording accelerations from both axles of a trailer and then analysing the spectra of the difference in the accelerations between the two axles. The effectiveness of the approach in detecting damage simulated as a loss in stiffness is also investigated. In addition, the sensitivity of the approach to the vehicle speed, road roughness class, bridge span length, changes in the equal axle properties and noise is investigated.

Strategies to improve the accuracy of vision measurement by teachers in rural Chinese secondary schoolchildren: Xichang Pediatric Refractive Error Study (X-PRES) report no. 6.

OBJECTIVE: To assess and improve the accuracy of lay screeners compared with vision professionals in detecting visual impairment in secondary schoolchildren in rural China. METHODS: After brief training, 32 teachers and a team of vision professionals independently measured vision in 1892 children in Xichang. The children also underwent vision measurement by health technicians in a concurrent government screening program. RESULTS: Of 32 teachers, 28 (87.5%) believed that teacher screening was worthwhile. Sensitivity (93.5%) and specificity (91.2%) of teachers detecting uncorrected presenting visual acuity of 20/40 or less were better than for presenting visual acuity (sensitivity, 85.2%; specificity, 84.8%). Failure of teachers to identify children owning but not wearing glasses and teacher bias toward better vision in children wearing glasses explain the worse results for initial vision. Wearing glasses was the student factor most strongly predictive of inaccurate teacher screening (P < .001). The sensitivity and specificity of the government screening program detecting low presenting visual acuity were 86.7% and 28.7%, respectively. CONCLUSIONS: Teacher vision screening after brief training can achieve accurate results in this setting, and there is support among teachers for screening. Screening of uncorrected rather than presenting visual acuity is recommended in settings with a high prevalence of corrected and uncorrected refractive error. Low specificity in the government program renders it ineffective.

Modelling the flow of congestive heart failure patients through a hospital system

The number of hospital admissions in England due to heart failure is projected to increase by over 50% during the next 25 years. This will incur greater pressures on hospital managers to allocate resources in an effective manner. A reliable indicator for measuring the quantity of resources consumed by hospital patients is their length of stay (LOS) in care. This paper proposes modelling the length of time heart failure patients spend in hospital using a special type of Markov model, where the flow of patients through hospital can be thought of as consisting of three stages of care—short-, medium- and longer-term care. If it is assumed that new admissions into the ward are replacements for discharges, such a model may be used to investigate the case-mix of patients in hospital and the expected patient turnover during some specified period of time. An example is illustrated by considering hospital admissions to a Belfast hospital in Northern Ireland, between 2000 and 2004.

BAILII, Legal Education and Open Access to Law

The British and Irish Legal Information Institute (BAILII) entered the online legal information landscape in 2001 with charitable status as a provider of UK and European judgments, and has over the past decade or so moved from a system quickly put together with any materials which could be found, to a system which provides a core resource to professionals in law. In this article we provide an overview for the law teacher of the system’s first years and we then look at whether usage in law schools has matched that of the professional, how the JISC funded Open Law project enabled development for law students, and where we might go in the future as part of the Legal Information Institute collective which operates under the ‘Free Access to Law’ banner.
As members of the Open Law team who sought funding, carried out the research and implemented the project, it seems to us that the project was generally successful. Our indications were that prior to Open Law the use of BAILII by students was low – it was not readily found or discussed by lecturers, was difficult to use, and generally less user friendly than it could have been. The changes implemented by Open Law appear to have changed that position considerably. However, our findings also indicate that there is much work to do to re-energise digital legal information as a legal education research field.

Living is Information Processing: From Molecules to Global Systems

We extend the concept that life is an informational phenomenon, at every level of organisation, from molecules to the global ecological system. According to this thesis: (a) living is information processing, in which memory is maintained by both molecular states and ecological states as well as the more obvious nucleic acid coding; (b) this information processing has one overall function-to perpetuate itself; and (c) the processing method is filtration (cognition) of, and synthesis of, information at lower levels to appear at higher levels in complex systems (emergence). We show how information patterns, are united by the creation of mutual context, generating persistent consequences, to result in 'functional information'. This constructive process forms arbitrarily large complexes of information, the combined effects of which include the functions of life. Molecules and simple organisms have already been measured in terms of functional information content; we show how quantification may be extended to each level of organisation up to the ecological. In terms of a computer analogy, life is both the data and the program and its biochemical structure is the way the information is embodied. This idea supports the seamless integration of life at all scales with the physical universe. The innovation reported here is essentially to integrate these ideas, basing information on the 'general definition' of information, rather than simply the statistics of information, thereby explaining how functional information operates throughout life. © 2013 Springer Science+Business Media Dordrecht.

Between Imaginary Lines: Violence and its Justifications at the Military Checkpoints in Occupied Palestine

Looking at one site, the Israeli checkpoints in the occupied Palestinian territory, this article seeks to understand the mechanisms by which violence can present itself as justifiable (or justified), even when it materializes within frames presumably set to annul it. We look at the checkpoints as a condensed microcosmos operating within two such frames. One is the prolonged IsraeliPalestinian ‘peace process’ (the checkpoints became a primary technology of control in the period following the beginning of the peace process), and the other is regulatory power (disciplinary and biopower), which in the Foucauldian framework presumably sidelines the violent form which sovereign power takes. We argue that the checkpoints, which dissect the Palestinian occupied territories into dozens of enclaves and which are one of the most effective and destructive means of control within the current stage of occupation, can be seen as more than obstacles in the way of Palestinian movement; we suggest that they also function as corrective technologies that are meant to fail. It is with this failure that violence can appear as justified. In order to show the operation of this embedded failure, we examine one mechanism operating within the checkpoints: ‘the imaginary line’. The imaginary line is both a component within, and an emblem of a mode of control that constantly undoes itself in order to summon violence. Since it is never visibly marked in the physical space, the imaginary line is bound to be unintentionally crossed, thereby randomly rendering Palestinians as ‘transgressors’ of the rule and thus facilitating eruptions of violence by the soldiers stationed at the checkpoints. This article proposes an analysis of this hidden demarcation of space in order to question the different relations between subjects and power which it both assumes and constitutes.

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial: study protocol for a randomized controlled trial

Background: Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI.

Methods/Design: Patients fulfilling the American-European Consensus Conference Definition of ALI will be randomized in a 1: 1 ratio to receive enteral simvastatin 80 mg or placebo once daily for a maximum of 28 days. Allocation to randomized groups will be stratified with respect to hospital of recruitment and vasopressor requirement. Data will be recorded by participating ICUs until hospital discharge, and surviving patients will be followed up by post at 3, 6 and 12 months post randomization. The primary outcome is number of ventilator-free days to day 28. Secondary outcomes are: change in oxygenation index and sequential organ failure assessment score up to day 28, number of non pulmonary organ failure free days to day 28, critical care unit mortality; hospital mortality; 28 day post randomization mortality and 12 month post randomization mortality; health related quality of life at discharge, 3, 6 and 12 months post randomization; length of critical care unit and hospital stay; health service use up to 12 months post-randomization; and safety. A total of 540 patients will be recruited from approximately 35 ICUs in the UK and Ireland. An economic evaluation will be conducted alongside the trial. Plasma and urine samples will be taken up to day 28 to investigate potential mechanisms by which simvastatin might act to improve clinical outcomes.

Cantilever steel post damaged by wind

An analysis for the cause of fracture failure of a cantilever steel sign post damaged by wind has been carried out. An unusual cause of failure has been identified, which is the subject of this paper. Microscopy and microanalysis of the fracture surface showed that the failure was due to pre-existing cracks, from the fabrication of the post. This conclusion was reached after detecting and analysing a galvanised layer on the fracture surfaces.