5,683 research outputs found
Collaborative working in highways major maintenance projects
Over the last decade, there has been a growing emphasis on collaborations and partnering in the construction industry. This has been embraced in the UK highways maintenance sector, with partnering promoted by the client, leading to the formation of alliances and partnering frameworks. One of these is the construction management framework (CMF), the preferred method of procurement for major maintenance projects in the Highways Agency’s areas 9 and 10. This paper compares two road and structure renewals schemes carried out using the CMF. The first scheme was carried out in 2004 as one of the first of its type to be undertaken by the CMF; the second was a similar project carried out in 2006. Documentation of the two projects was reviewed to identify the benefits that were gained through working in collaboration, and if there was an improvement in performance as the framework became more established. The research considered key performance indicators, including cost and time predictability measures, respect for people surveys, innovations and lessons learned discussed at the time of the projects, and instructions for changes to works information. Data collected from both schemes show improvements in measurement and culture fostered by the CMF, and the advantages of the processes used are illustrated
Kwashiorkor and Intellectual Development
Forty Cape Coloured children who had been hospitalized for kwashiorkor in infancy were compared with their siblings on an intelligence test battery at the 10th year of follow-up. No significant differences in intelligence test performance were noted. A significant discrepancy between the intelligence test score and the drawing score in late-onset cases may be due to affective factors. The groups were similar in terms of height, weight and head circumference. The differences between well nourished and poorly nourished groups found by previous investigators may be accounted for by the independent operation of non-nutritive variables in the social and emotional environment. The use of intrafamilial controls in the present study minimized these influences, as well as possible genetic factors in intellectual development.S. Afr. Med. J., 45, 1413 (1971
Costs of mitigating CO2 emissions from passenger aircraft
In response to strong growth in air transportation CO2 emissions, governments and industry began to explore and implement mitigation measures and targets in the early 2000s. However, in the absence of rigorous analyses assessing the costs for mitigating CO2 emissions, these policies could be economically wasteful. Here we identify the cost-effectiveness of CO2 emission reductions from narrow-body aircraft, the workhorse of passenger air transportation. We find that in the US, a combination of fuel burn reduction strategies could reduce the 2012 level of life cycle CO2 emissions per passenger kilometre by around 2% per year to mid-century. These intensity reductions would occur at zero marginal costs for oil prices between US$50–100 per barrel. Even larger reductions are possible, but could impose extra costs and require the adoption of biomass-based synthetic fuels. The extent to which these intensity reductions will translate into absolute emissions reductions will depend on fleet growth
Not just another environmental education tool - The urban jungle: Development and evaluation
No Abstract
The acceptability and feasibility of using a 3D body size scale to initiate conversations about weight in toddlerhood: a mixed-methods study
Background: Health Care Professionals struggle to initiate conversations about overweight in toddlerhood. A novel 3D body size scale (3D BSS) may facilitate engagement with this topic during pediatric appointments.
Objectives: To explore barriers and facilitators to using the 3D BSS through a mixedmethods design.
Methods: For the qualitative phase, parents of toddlers (n = 38) participated in semistructured interviews introducing the 3D BSS of 4–5-year-old children. For the quantitative phase, pre- and post-interview questionnaires were administered to ascertain
the acceptability of the 3D BSS.
Results: Parents rated the 3D BSS as “very” (n = 20, 52.6%) to “moderately” (n = 12,
31.6%) acceptable. Thematic analysis revealed four barriers to acceptability: i) the
sensitive nature of child weight, ii) the belief that weight does not determine health,
iii) the visual normalisation of overweight and iv) the need to account for individual
variation in growth patterns. However, these barriers could be overcome through
three facilitators: i) the provision of expert guidance ii) the value of simple tools, and
iii) tailoring conversations to familial needs.
Conclusions: Parents considered the 3D BSS an acceptable visual resource to discuss
child weight during routine appointments. However, the acceptability of the tool was
conditional on a sensitive, collaborative, and tailored delivery approach
Salvage Fractionated Stereotactic Re-irradiation (FSRT) for Patients with Recurrent High Grade Gliomas Progressed after Bevacizumab Treatment
Purpose/Objectives: Bevacizumab failure is a major clinical problem in the manage- ment of high grade gliomas (HGG), with a median overall survival of less than 4 months (m). This study evaluated the efficacy of fractionated stereotactic re-irradiation (FSRT) for patients with HGG after progression on Bevacizumab.
Materials/Methods: Retrospective review was conducted of patients treated with FSRT after progression on bevacizumab. A total of 36 patients were identified. FSRT was most commonly delivered in 3.5 Gy fractions to a total dose of 35 Gy. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were utilized as study endpoints. Univariate and multivariate analysis was performed.
Results: Among the 36 patients, 31 patients had recurrent glioblastoma, and 5 patients had recurrent anaplastic astrocytoma. The median time from initial bevacizumab treatment to FSRT was 8.5 m (range 2.3 – 32.0 m). The median plan target volume for FSRT was 27.5 cc (range 1.95 – 165 cc). With a median follow up of 20.4 m, the overall survival of the patients since initial diagnosis was also 24.9 m. The median overall survival after initiation of bevacizumab was 13.4 months. The median overall survival from FSRT was 4.8 m. FSRT treatment was well tolerated with no Grade \u3e3 toxicity.
Conclusions: Favorable outcomes were observed in patients with recurrent HGG who received salvage FSRT after bevacizumab failure. The treatment was well tolerated. Prospective study is warranted to further evaluate the efficacy of salvage FSRT for selected patients with recurrent HGG amenable to FSRT, who had failed bevacizumab treatment
Therapeutic Myeloperoxidase Inhibition Attenuates Neutrophil Activation, ANCA-Mediated Endothelial Damage, and Crescentic GN
BACKGROUND: Myeloperoxidase released after neutrophil and monocyte activation can generate reactive oxygen species, leading to host tissue damage. Extracellular glomerular myeloperoxidase deposition, seen in ANCA-associated vasculitis, may enhance crescentic GN through antigen-specific T and B cell activation. Myeloperoxidase-deficient animals have attenuated GN early on, but augmented T cell responses. We investigated the effect of myeloperoxidase inhibition, using the myeloperoxidase inhibitor AZM198, to understand its potential role in treating crescentic GN.
METHODS: We evaluated renal biopsy samples from patients with various forms of crescentic GN for myeloperoxidase and neutrophils, measured serum myeloperoxidase concentration in patients with ANCA-associated vasculitis and controls, and assessed neutrophil extracellular trap formation, reactive oxygen species production, and neutrophil degranulation in ANCA-stimulated neutrophils in the absence and presence of AZM198. We also tested the effect of AZM198 on ANCA-stimulated neutrophil-mediated endothelial cell damage in vitro, as well as on crescentic GN severity and antigen-specific T cell reactivity in the murine model of nephrotoxic nephritis.
RESULTS: All biopsy specimens with crescentic GN had extracellular glomerular myeloperoxidase deposition that correlated significantly with eGFR and crescent formation. In vitro, AZM198 led to a significant reduction in neutrophil extracellular trap formation, reactive oxygen species production, and released human neutrophil peptide levels, and attenuated neutrophil-mediated endothelial cell damage. In vivo, delayed AZM198 treatment significantly reduced proteinuria, glomerular thrombosis, serum creatinine, and glomerular macrophage infiltration, without increasing adaptive T cell responses.
CONCLUSIONS: Myeloperoxidase inhibition reduced neutrophil degranulation and neutrophil-mediated endothelial cell damage in patients with ANCA-associated vasculitis. In preclinical crescentic GN, delayed myeloperoxidase inhibition suppressed kidney damage without augmenting adaptive immune responses, suggesting it might offer a novel adjunctive therapeutic approach in crescentic GN
Prescription Drugs Associated with Reports of Violence Towards Others
CONTEXT: Violence towards others is a seldom-studied adverse drug event and an atypical one because the risk of injury extends to others. OBJECTIVE: To identify the primary suspects in adverse drug event reports describing thoughts or acts of violence towards others, and assess the strength of the association. METHODOLOGY: From the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) data, we extracted all serious adverse event reports for drugs with 200 or more cases received from 2004 through September 2009. We identified any case report indicating homicide, homicidal ideation, physical assault, physical abuse or violence related symptoms. MAIN OUTCOME MEASURES: Disproportionality in reporting was defined as a) 5 or more violence case reports, b) at least twice the number of reports expected given the volume of overall reports for that drug, c) a χ2 statistic indicating the violence cases were unlikely to have occurred by chance (p<0.01). RESULTS: We identified 1527 cases of violence disproportionally reported for 31 drugs. Primary suspect drugs included varenicline (an aid to smoking cessation), 11 antidepressants, 6 sedative/hypnotics and 3 drugs for attention deficit hyperactivity disorder. The evidence of an association was weaker and mixed for antipsychotic drugs and absent for all but 1 anticonvulsant/mood stabilizer. Two or fewer violence cases were reported for 435/484 (84.7%) of all evaluable drugs suggesting that an association with this adverse event is unlikely for these drugs. CONCLUSIONS: Acts of violence towards others are a genuine and serious adverse drug event associated with a relatively small group of drugs. Varenicline, which increases the availability of dopamine, and antidepressants with serotonergic effects were the most strongly and consistently implicated drugs. Prospective studies to evaluate systematically this side effect are needed to establish the incidence, confirm differences among drugs and identify additional common features
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AMPK and uterine artery vasodilation
Genes near adenosine monophosphate-activated protein kinase-α1 (PRKAA1) have been implicated in the greater uterine artery (UtA) blood flow and relative protection from fetal growth restriction seen in altitude-adapted Andean populations. Adenosine monophosphate-activated protein kinase (AMPK) activation vasodilates multiple vessels but whether AMPK is present in UtA or placental tissue and influences UtA vasoreactivity during normal or hypoxic pregnancy remains unknown. We studied isolated UtA and placenta from near-term C57BL/6J mice housed in normoxia (n = 8) or hypoxia (10% oxygen, n = 7-9) from day 14 to day 19, and placentas from non-labouring sea level (n = 3) or 3100 m (n = 3) women. Hypoxia increased AMPK immunostaining in near-term murine UtA and placental tissue. RT-PCR products for AMPK-α1 and -α2 isoforms and liver kinase B1 (LKB1; the upstream kinase activating AMPK) were present in murine and human placenta, and hypoxia increased LKB1 and AMPK-α1 and -α2 expression in the high- compared with low-altitude human placentas. Pharmacological AMPK activation by A769662 caused phenylephrine pre-constricted UtA from normoxic or hypoxic pregnant mice to dilate and this dilatation was partially reversed by the NOS inhibitor l-NAME. Hypoxic pregnancy sufficient to restrict fetal growth markedly augmented the UtA vasodilator effect of AMPK activation in opposition to PE constriction as the result of both NO-dependent and NO-independent mechanisms. We conclude that AMPK is activated during hypoxic pregnancy and that AMPK activation vasodilates the UtA, especially in hypoxic pregnancy. AMPK activation may be playing an adaptive role by limiting cellular energy depletion and helping to maintain utero-placental blood flow in hypoxic pregnancy.Funding for these studies was provided by the Wellcome Trust (084804/2/08/Z) to G.J.B., the British Heart Foundation and the Wellcome Trust to D.A.G., the Biotechnology and Biological Sciences Research Council (BBSRC) to A.L.F., a UK Wellcome Trust Programme Grant (WT081195MA) to A.M.E. and A.D.M., a BBSRC studentship and in vivo skills award to J.S.H., a National Health Medical Research Council and Centre for Trophoblast Research fellowship to A.N.S.-P., and a NIH RO1 grant (HLBI-079647) to L.G.M. along with sabbatical support from Wake Forest University.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1113/JP27099
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