Safety culture in defence explosive ordnance: developing a safety climate measure

It is increasingly recognised within high-consequence industries that a positive safety culture is strongly linked to various safety outcomes and performance indicators. Explosive ordnance (EO) is an area that demands a high level of safety culture, indeed it is a reputational and operational necessity. This paper introduces a measure of safety climate tailored to the EO domain. The paper describes the background to the study, the development of items, and the subsequent factorial validation of scales on the basis of a sample of 272 EO personnel. The factor structure that emerged was very similar to the postulated structure of 14 climate dimensions. These 14 dimensions were shown to represent three meta-themes in the data: Safety Awareness and Responsibility (8 subscales), Safety Resources issues (3 subscales), and Safety System issues (3 subscales). The authors are confident that the EO Safety Survey is a valid, reliable and powerful tool that will support the goal of holistic reform of the EO domain. The EO Safety Survey will inform and enable tailored safety intervention efforts, improved compliance monitoring, and benchmarking studies that, collectively, will enhance the management of the human factors issues that impact on EO work

C*-Algebras with the Approximate Positive Factorization Property

We say that a unital C*-algrebra A has the approximate positive factorization property (APFP) if every element of A is a norm limit of products of positive elements of A. (There is also a definition for the nonunital case.) T. Quinn has recently shown that a unital AF algebra has the APFP if and only if it has no finite dimensional quotients. This paper is a more systematic investigation of C*-algebras with the APFP. We prove various properties of such algebras. For example: They have connected invertible group, trivial K_1, and stable rank 1. In the unital case, the K_0 group separates the tracial states. The APFP passes to matrix algebras. and if I is an ideal in A such that I and A/I have the APFP, then so does A. We also give some new examples of C*-algebras with the APFP, including type II_1 factors and infinite-dimensional simple unital direct limits with slow dimension growth, real rank zero, and trivial K_1 group. An infinite- dimensional simple unital direct limit with slow dimension growth and with the APFP must have real rank zero, but we also give examples of unital algebras with the APFP which do not have real rank zero. Our analysis also leads to the introduction of a new concept of rank for a C*-algebra that may be of interest in the future.Comment: plain TeX; 19 page

Why advanced buildings don't work?

The intent of policy is to achieve robust comfortable low energy buildings. However there are obvious policy disconnects and, where there is evidence, it appears that in general advanced buildings do not achieve their intended performance. There are many industry and policy initiatives aimed at improving industry processes such as: Soft Landings, BREEAM, LEED, Green Star, AGBR and BIM. In this paper the performance of buildings likely to be promoted by current policy is investigated and a number of significant and recurring problems identified. The possibility that these problems will be resolved by current initiatives is discussed and it is concluded that important gaps remain to be addressed

Co-Amenability of compact quantum groups

We study the concept of co-amenability for a compact quantum group. Several conditions are derived that are shown to be equivalent to it. Some consequences of co-amenability that we obtain are faithfulness of the Haar integral and automatic norm-boundedness of positive linear functionals on the quantum group's Hopf *-algebra (neither of these properties necessarily holds without co-amenability).Comment: 25 pages. LaTe

The influence of sex on the in vivo and in vitro effects of treprostinil in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive and fatal vascular disease that is more prevalent in women than men. The underlying pathology of the disease involves various factors, including genetic risk (i.e. bone morphogenetic protein receptor type II (BMPR-II) mutations) as well as the influence of hormones such as estrogen. Among the frontline treatments for PAH is prostacyclin therapy; however, the short half-life and associated problems with the need for continuous intravenous administration of synthetic prostacyclin have led to the development of newer analogues such as treprostinil. These have the advantages of a longer half-life and the possibility of subcutaneous and inhaled administration. Mortality rates for PAH are still high despite advancements in treatment, with male survival rates remaining lower than females. The BMPR-II signalling pathway may underlie some of the sex disparity that exists in incidence of PAH. However, patient responses to treatments for PAH have also demonstrated sex-specific effects. A key aim of this study was to identify the influence that sex may have on the actions of treprostinil with in-vivo and in-vitro models of PH. The ability to target treatment to specific sub-cohorts of PH is important to maximise the therapeutic effect of treprostinil. A greater understanding of how the effects of treprostinil are mediated could assist this objective. To examine any potential influence of sex on the effects of treprostinil, we examined the chronic hypoxic model of pulmonary hypertension (PH). Female and male rats were dosed with sub-cutaneously implanted pellets releasing treprostinil at 100ng/kg/min or 400ng/kg/min. Under hypoxic conditions both male and female rats had increases in right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH) and pulmonary artery remodelling. 100ng/kg/min of treprostinil partially reversed RVSP, RVH and pulmonary artery remodelling in female hypoxic rats but not in male rats. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed that a possible mechanism of treprostinil was increasing BMPR-II signalling, specifically Id1 and Id3 (inhibitor of DNA binding protein 1/3). This was only observed in female hypoxic rats. Despite no difference in terminal plasma levels of treprostinil, hypoxic males remained unaffected by treprostinil at 100ng/kg/min. However, 400ng/kg/min of treprostinil led to slightly greater decreases in RVSP, RVH and remodelling indices in female rats, also it partially reversed RVSP, RVH and remodelling in male rats. Taqman qRT-PCR of the prostaglandin receptors demonstrated an increase in prostaglandin E2 receptor 2 (EP2) under hypoxic conditions with 100ng/kg/min and 400ng/kg/min treprostinil treatment, specific to female rats. Also under hypoxic conditions female and male rats had significant increases in mRNA expression of potassium two pore domain channel subfamily K (KCNK3). To translate clinical relevance from the in-vivo findings, the influence of sex on treprostinil was investigated in human pulmonary artery smooth muscle cells (hPASMCs) taken from non-PAH (control) and PAH patients. In female control hPASMCs FBS (fetal bovine serum) induced proliferation was partially ablated by treprostinil; this effect was only observed in male control hPASMCs at the highest treprostinil concentration (10µM). In patient hPASMCs, treprostinil had a similar effect in reducing FBS-induced proliferation in both female and males. The addition of a low dose (30nM) of endothelin-1 (ET-1) increased the anti-proliferative effect of treprostinil, specifically, in female control hPASMCs. The addition of a dual endothelin receptor antagonist (SB-217242) partially reduced the anti-proliferative effect of treprostinil in combination with ET-1. Taqman qRT-PCR and western blot analysis demonstrated no difference between sexes or hPASMC groups in the expression of the prostaglandin receptors. Using receptor specific antagonists, it was determined that the anti-proliferative actions of treprostinil in PAH patient hPASMCs were partially mediated via the EP2 receptor. However, in female control hPASMCs, the IP receptor was primarily responsible for this effect. BMPR-II signalling was investigated to ascertain its role in the anti-proliferative effects of treprostinil. Taqman qRT-PCR indicated treprostinil (100nM and 1µM) induced increases in Id1 and Id3 mRNA in female control hPASMCs, this did not occur in male control hPASMCs. Treprostinil (100nM and 1µM) led to Id3 mRNA increases in female PAH patient hPASMCs, whereas in male PAH patient hPASMCs treprostinil (1µM) led to a significant Id3 mRNA increase. Western blots indicated that Id3 was upregulated by treprostinil (1µM) stimulation in female control and female PAH hPASMCs vs non-stimulated hPASMCs; this effect was not observed in males. The combination of ET-1 and treprostinil did not influence BMPR-II signalling. After 24 hours of treprostinil stimulation increased Id3 mRNA expression was observed in all hPASMCs groups. Treprostinil only increased Id1 mRNA in PAH patient hPASMCs. Although western blots confirmed treprostinil (100nM and 1µM) mediated increases in Id1 protein expression in female control hPASMCs. Treprostinil (100nM and 1µM) increased Id3 protein expression in female control and female PAH patient hPASMCs. Treprostinil (1µM) in combination with ET-1 led to a significant increase in Id3 protein expression in male control hPASMCs. As with 72-hour treprostinil stimulation, BMPR-II signalling was not influenced by the combination of ET-1 and treprostinil in the other hPASMC groups. The increased BMPR-II signalling in female control and female PAH patient hPASMCs at 24 hours led to the investigation of prostaglandin receptors role in activating BMPR-II signalling. After 24-hours of stimulation with treprostinil (100nM), Id protein induction was partially blocked by dual antagonism of the IP and EP2 receptor in both female control and female PAH patient hPASMCs. To summarise these findings, we have identified sex differences in the action of treprostinil in both in-vivo and in-vitro models of PH. Treatment with a low dose (100ng/kg/min) of treprostinil led to a significant reduction in chronic hypoxic induced PH in female rats but not in males. These differences are driven partially by increases in BMPR-II signalling. Treatment with a higher dose (400ng/kg/min) of treprostinil led to significant reductions in chronic hypoxic PH in both female and male rats. In hPASMCs the results demonstrate that treprostinil can induce the Id proteins of the BMPR-II signalling pathway and that this may account for the greater anti-proliferative effect observed in female control hPASMCs. The induction of the Id proteins was found to be partially mediated by activation of the IP and EP2 prostaglandin receptors. The results suggest that sex may influence the beneficial effects of treprostinil in an in-vivo model of PH and in hPASMCs

Computational studies of the transverse structure of AGN jets

Both the emission properties and the evolution of the radio jets of Active Galactic Nuclei are dependent on the magnetic (B) fields that thread them. A number of observations of AGN jets suggest that the B fields they carry have a significant helical component, at least on parsec scales. This thesis uses a model, first proposed by Laing and then developed by Papageorgiou, to explore how well the observed properties of AGN jets can be reproduced by assuming a helical B field with three parameters; pitch angle, viewing angle and degree of entanglement. This model has been applied to multifrequency Very Long Baseline Interferometry (VLBI) observations of the AGN jets of Markarian 501 and M87, making it possible to derive values for the helical pitch angle, the viewing angle and the degree of entanglement for these jets. Faraday rotation measurements are another important tool for investigating the B fields of AGN jets. A helical B field component should result in a systematic gradient in the observed Faraday rotation across the jet. Real observed radio images have finite resolution; typical beam sizes for cm-wavelength VLBI observations are often comparable to or larger than the intrinsic jet widths, raising questions about how well resolved a jet must be in the transverse direction in order to reliably detect transverse Faraday-rotation structure. This thesis presents results of Monte Carlo simulations of Faraday rotation images designed to directly investigate this question, together with a detailed investigation into the probabilities of observing spurious Faraday Rotation gradients as a result of random noise and finite resolution. These simulations clearly demonstrate the possibility of detecting transverse Faraday-rotation structures even when the intrinsic jet widths are appreciably smaller than the beam width

Paracetamol metabolism in postoperative patients

Introduction: Despite being available for more than 50 years, there is still much to learn about paracetamol. Postoperative analgesic regimens that maintain good pain control while minimising exposure to opiates are beneficial and paracetamol has had a resurgence in this role since an IV formulation came to market. However there is evidence to suggest currently licensed doses are sub-therapeutic, especially when administered orally or rectally. Higher, unlicensed doses are now being advocated but, prior to this study, there was little evidence of their safety in surgical patients. When assessing drug safety in surgical patients a number of surgery and patient related factors influence results, and these must be considered. Methods: Major and intermediate surgical patients were recruited from two hospitals in Ireland. They were administered IV paracetamol at either 9g or 4g daily doses. In addition they received daily sub therapeutic doses of four other medicines to indicate the activity of their CYP450 enzymes that are involved in paracetamol metabolism. Urine and blood samples were collected to determine paracetamol pharmacokinetics, CYP450 activity, inflammatory cytokine concentration and for evidence of hepatotoxicity. Results: There were 33 patients that participated in the study. There was no evidence of clinically significant hepatotoxicity occurring in any patient during the study period, but there could have been changes following this time. Paracetamol disposition was shown to change, however half-life remained relatively constant. There were a number of changes to the way paracetamol was metabolised following surgery that maintained this rate of elimination. Conclusion: Doses of up to 9g per day given to major surgical patients for up to five days postoperatively produced no evidence of hepatotoxicity. Further research is warranted to determine the clinical utility of these higher dose

Exploring the failing right ventricle in pulmonary hypertension by cardiac magnetic resonance: an in vivo study utilizing Macitentan

Cardiac magnetic resonance (CMR) imaging is used to assess the right ventricle (RV) of pulmonary hypertensive (PH) patients and more recently to track changes in response to therapy. We wished to investigate if repeat CMRs could be used to assess ventricular changes in the Sugen 5416 hypoxic (Su/Hx) rat model of PH treated with the dual endothelin receptor antagonist Macitentan. Male Sprague Dawley Su/Hx rats were dosed for 3 weeks with either vehicle or Macitentan (30 mg/kg) daily, control rats received only vehicle. All rats underwent three CMR scans; before treatment, 2 weeks into treatment, and end of the study. A separate group of Su/Hx and control rats, treated as above, underwent terminal hemodynamic measurements. Using terminal and CMR measurements, Macitentan was found to lower RV systolic pressure pulmonary artery remodeling and increase RV ejection fraction but not change RV hypertrophy (RVH). Repeat CMRs determined that Su/Hx rats treated with Macitentan had significantly reversed RVH via reducing RV mass as well as reducing elevated left ventricular eccentricity index; reductions in RV mass were also observed in Su/Hx vehicle rats exposed to normoxic conditions. We have demonstrated that repeat CMRs can be used to assess the volume and structural changes in the ventricles of the Su/Hx rat model. Using repeat CMRs has allowed us to build a more complete picture of the response of the RV and the left ventricle to treatment. It is unknown if these effects are a consequence of direct action on the RV or secondary to improvements in the lung vasculature