1,312 research outputs found

    Using immersive audio and vibration to enhance remote diagnosis of mechanical failure in uncrewed vessels.

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    There is increasing interest in the maritime industry in the potential use of uncrewed vessels to improve the efficiency and safety of maritime operations. This leads to a number of questions relating to the maintenance and repair of mechanical systems, in particular, critical propulsion systems which if a failure occurs could endanger the vessel. While control data is commonly monitored remotely, engineers on board ship also employ a wide variety of sensory feedback such as sound and vibration to diagnose the condition of systems, and these are often not replicated in remote monitoring. In order to assess the potential for enhancement of remote monitoring and diagnosis, this project simulated an engine room (ER) based on a real vessel in Unreal Engine 4 for the HTC ViveTM VR headset. Audio was recorded from the vessel, with mechanical faults synthesized to create a range of simulated failures. In order to simulate operational requirements, the system was remotely fed data from an external server. The system allowed users to view normal control room data, listen to the overall sound of the space presented spatially over loudspeakers, isolate the sound of particular machinery components, and feel the vibration of machinery through a body worn vibration transducer. Users could scroll through a 10-hour time history of system performance, including audio, vibration and data for snapshots at hourly intervals. Seven experienced marine engineers were asked to assess several scenarios for potential faults in different elements of the ER. They were assessed both quantitatively regarding correct fault identification, and qualitatively in order to assess their perception of usability of the system. Users were able to diagnose simulated mechanical failures with a high degree of accuracy, mainly utilising audio and vibration stimuli, and reported specifically that the immersive audio and vibration improved realism and increased their ability to diagnose system failures from a remote location

    Feasibility of a self-completed history questionnaire in women requesting repeat combined hormonal contraception.

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    OBJECTIVE: To measure agreement between the client's and the clinician's responses to questions regarding client history as answered on a questionnaire based on the UK Medical Eligibility Criteria for Contraceptive Use (UKMEC) for combined hormonal contraception (CHC). METHODS: Clients aged 18 years and over, attending a central London community contraceptive clinic requesting a repeat supply of CHC, completed a history questionnaire and an evaluation form. Clinicians then completed their copy of the same questionnaire during the consultation. Percentage agreement and the Kappa statistic were used to assess the level of client-clinician agreement. RESULTS: Data from 328 client-clinician pairs were analysed. Agreement was above 93% for all identified risk factors. There was complete agreement for thrombosis, diabetes, stroke, cancer and liver problems. Least agreement was noted in the recording of migraine and abnormal bleeding. For all risk factors except smoking, the proportion of clients reporting a risk factor was more than the proportion of clinicians reporting a risk factor. No clinically important information relevant to a particular client's use of CHC was missed and none of them would have been wrongly prescribed the CHC based just on their self-completed questionnaires. Most women (97%) were happy with this method of history taking. CONCLUSIONS: A self-completed history questionnaire is acceptable to women and can potentially replace traditional routine medical history taking for continuing CHC. Women completed the questionnaire with a high degree of reliability. There was complete client-clinician agreement on UKMEC Category 4 criteria. Overall, clients reported more risk factors than clinicians, which increases the safety of the questionnaire

    Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

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    Background: A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. <p/>Methods: Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). <p/>Results: 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m2. MTD was 10 mg/m2; DLTs at 12 (2/4 patients) and 10 mg/m2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and Cmax from 1--10 mg/m2. Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. <p/>Conclusions: TP300 had predictable hematologic toxicity, and diarrhea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage

    Squirrelpox virus: assessing prevalence, transmission and environmental degradation

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    Red squirrels (Sciurus vulgaris) declined in Great Britain and Ireland during the last century, due to habitat loss and the introduction of grey squirrels (Sciurus carolinensis), which competitively exclude the red squirrel and act as a reservoir for squirrelpox virus (SQPV). The disease is generally fatal to red squirrels and their ecological replacement by grey squirrels is up to 25 times faster where the virus is present. We aimed to determine: (1) the seropositivity and prevalence of SQPV DNA in the invasive and native species at a regional scale; (2) possible SQPV transmission routes; and, (3) virus degradation rates under differing environmental conditions. Grey (n = 208) and red (n = 40) squirrel blood and tissues were sampled. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) techniques established seropositivity and viral DNA presence, respectively. Overall 8% of squirrels sampled (both species combined) had evidence of SQPV DNA in their tissues and 22% were in possession of antibodies. SQPV prevalence in sampled red squirrels was 2.5%. Viral loads were typically low in grey squirrels by comparison to red squirrels. There was a trend for a greater number of positive samples in spring and summer than in winter. Possible transmission routes were identified through the presence of viral DNA in faeces (red squirrels only), urine and ectoparasites (both species). Virus degradation analyses suggested that, after 30 days of exposure to six combinations of environments, there were more intact virus particles in scabs kept in warm (25°C) and dry conditions than in cooler (5 and 15°C) or wet conditions. We conclude that SQPV is present at low prevalence in invasive grey squirrel populations with a lower prevalence in native red squirrels. Virus transmission could occur through urine especially during warm dry summer conditions but, more notably, via ectoparasites, which are shared by both species

    Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus

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    BACKGROUND: Diabetic nephropathy is a serious complication of diabetes mellitus and is associated with considerable morbidity and high mortality. There is increasing evidence to suggest that dysregulation of the epigenome is involved in diabetic nephropathy. We assessed whether epigenetic modification of DNA methylation is associated with diabetic nephropathy in a case-control study of 192 Irish patients with type 1 diabetes mellitus (T1D). Cases had T1D and nephropathy whereas controls had T1D but no evidence of renal disease. METHODS: We performed DNA methylation profiling in bisulphite converted DNA from cases and controls using the recently developed Illumina Infinium(R) HumanMethylation27 BeadChip, that enables the direct investigation of 27,578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14,495 genes. RESULTS: Singular Value Decomposition (SVD) analysis indicated that significant components of DNA methylation variation correlated with patient age, time to onset of diabetic nephropathy, and sex. Adjusting for confounding factors using multivariate Cox-regression analyses, and with a false discovery rate (FDR) of 0.05, we observed 19 CpG sites that demonstrated correlations with time to development of diabetic nephropathy. Of note, this included one CpG site located 18 bp upstream of the transcription start site of UNC13B, a gene in which the first intronic SNP rs13293564 has recently been reported to be associated with diabetic nephropathy. CONCLUSION: This high throughput platform was able to successfully interrogate the methylation state of individual cytosines and identified 19 prospective CpG sites associated with risk of diabetic nephropathy. These differences in DNA methylation are worthy of further follow-up in replication studies using larger cohorts of diabetic patients with and without nephropathy

    Orthopaedic health status of horses from 8 riding schools - a pilot study

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    <p>Abstract</p> <p>Background</p> <p>Orthopaedic injury is the most common reason for lameness and wastage in sport and leisure horses. Studies on racehorses have shown differences in injury risk between trainers and training strategies. The aim was to study between riding school variation in orthopaedic health status by clinical examination and horses age, and control for change of examiner, in schools with previous high (n = 4) and low (n = 4) insurance utilisation.</p> <p>Methods</p> <p>Horses (n = 99) at 8 riding schools were examined for conformation, movement in all gaits, standing flexion tests and palpation by two veterinary surgeons (in some schools only one). Indexes of findings were created for total health, movements, limbs, conformation and back palpation.</p> <p>Results</p> <p>Logistic regression analyses showed that findings increased with age (walk, trot, canter, conformation left hind limb, palpation fore limbs, hooves and flexion tests) or decreased with age (conformation right fore limb). Significant differences in findings were found between riding schools and examiner for seven and eight criteria each (partly overlapping). Increasing indexes were significantly associated with one examiner (total health, movements, back palpation), increasing age (total health, movements) or more time at the school (limbs). The back palpation index was highest at 5 < 8 years since acquisition.</p> <p>Conclusion</p> <p>The age distribution differed markedly between riding schools and age affected several types of findings. This, combined with the two opposite groups of insurance use, shows that schools with low insurance utilisation had previously been able to "avoid" using the insurance, maybe even on similar types of cases if these were more promptly/differently handled indicating differential coverage of disease data in the insurance database. The examiner effect was clearly demonstrated. For some findings, the amount of clinical observations differed by school, even when examiner and age was adjusted for. Most findings were of minor importance, including slight movement irregularities. Orthopaedic status varies between riding schools. We hypothesize that this is associated with management factors that warrant further study.</p

    Mergers, Deregulation and Cost Savings in the U.S. Rail Industry

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    The success of deregulation in creating a viable private rail freight system in the ?U.S. since 1979 is relatively undisputed. Deregulation has proceeded in three ways: (i) eased rate setting restrictions; (ii) simplified merger applications and approval procedures; and (iii) relaxed route abandonment policies. In this paper we attempt to disentangle the effects of deregulation on rail costs from those directly attributable to mergers and acquisitions. We employ a translog variable cost function, based on an unbalanced panel data set of annual observations for major U.S. Class I railroads from 1974 to 1986. We find that both deregulation and mergers contributed significantly to cost savings. However, of the accumulated cost savings achieved by the six major firms involved in mergers post-deregulation, we estimate that by 1986 about 91% of the reduction in accumulated costs is due to deregulation, and about 9% is directly due to mergers and acquisitions (which in turn were facilitated by regulatory reforms). In terms of factor biases, we find that both deregulation and mergers resulted in a substantial labor-saving bias; the point estimate of the deregulation labor-saving bias is larger than that for mergers, but we were not able to estimate this bias precisely. We conclude that mergers were not a prerequisite for railroads being able to achieve substantial cost and productivity improvements in our 1974-1986 sample period. Deregulation also had an enormous direct impact; indeed, its impact appears to have been much larger.

    The Activation Status of Neuroantigen-specific T Cells in the Target Organ Determines the Clinical Outcome of Autoimmune Encephalomyelitis

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    The clinical picture of experimental autoimmune encephalomyelitis (EAE) is critically dependent on the nature of the target autoantigen and the genetic background of the experimental animals. Potentially lethal EAE is mediated by myelin basic protein (MBP)–specific T cells in Lewis rats, whereas transfer of S100β- or myelin oligodendrocyte glycoprotein (MOG)–specific T cells causes intense inflammatory response in the central nervous system (CNS) with minimal disease. However, in Dark Agouti rats, the pathogenicity of MOG-specific T cells resembles the one of MBP-specific T cells in the Lewis rat. Using retrovirally transduced green fluorescent T cells, we now report that differential disease activity reflects different levels of autoreactive effector T cell activation in their target tissue. Irrespective of their pathogenicity, the migratory activity, gene expression patterns, and immigration of green fluorescent protein+ T cells into the CNS were similar. However, exclusively highly pathogenic T cells were significantly reactivated within the CNS. Without local effector T cell activation, production of monocyte chemoattractants was insufficient to initiate and propagate a full inflammatory response. Low-level reactivation of weakly pathogenic T cells was not due to anergy because these cells could be activated by specific antigen in situ as well as after isolation ex vivo

    Effect of crack-like defects on the fracture behaviour of Wire + Arc additively manufactured nickel-base Alloy 718

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    The fabrication of large components using a high deposition rate, near-net shape process like Wire + Arc Additive Manufacturing (WAAM) is a promising option for many industries, due to the potential for reduction in material wastage and shorter lead times in comparison to conventional methods. Specialist materials like nickel-base superalloys, which are typically used in high temperature and corrosive environments, are particularly attractive options due to their high raw material costs. Although nickel-base Alloy 718 seems well suited to the process due to its good weldability, process-induced defects can arise from unfavourable deposition conditions and elimination of these defects may not always be possible. In WAAM Alloy 718 deposited under such conditions, crack-like defects with planar morphology and hot cracking characteristics were observed. These defects were observable using conventional non-destructive testing techniques and displayed directionality relating to the deposition path. The fracture behaviour of WAAM Alloy 718 containing these defects was “semi-stable” – a mixture of fracture instability and stable crack extension. The apparent fracture toughness of WAAM Alloy 718 containing these defects was found to be anisotropic, which can be attributed to the interaction of the notched crack with pre-existing defects. WAAM Alloy 718 displayed an apparent fracture toughness comparable to that of wrought Alloy 718 when notched perpendicular to the defects; but only half that of wrought when notched parallel to the defects. Therefore, careful consideration of defect orientation and their effects on mechanical properties is important in assessing the fitness-for-service of WAAM Alloy 71
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