Our common estate: Planning for land in large-scale urban development

This paper explores the role that land plays in the process of large-scale urban development, with a particular focus on England. In doing so, it looks at the role that both strategic and non-strategic land can play in the process. It considers the current context and identifies the need for new development models to come forward. The paper proposes one means by which public-sector land, a ‘common estate’ to the extent that assets are held indivisibly by various public-sector organisations for the provision of goods and services, could be better deployed to help address the housing delivery challenges faced

Activated protein C: cost-effective or costly?

The authors offer a commentary on the study by Dhainaut et al. on the cost-effectiveness of activated protein C in severe sepsis. Using data from "real world" conditions, the results of this economic evaluation are consistent with previous analyses, and highlight the need for "real world" investigations of new health technologies in critical care

Identification of a serum biomarker panel for the differential diagnosis of cholangiocarcinoma and primary sclerosing cholagnitis

The non-invasive differentiation of malignant and benign biliary disease is a clinical challenge. Carbohydrate antigen 19-9 (CA19-9), leucine-rich α2-glycoprotein (LRG1), interleukin 6 (IL6), pyruvate kinase M2 (PKM2), cytokeratin 19 fragment (CYFRA21.1) and mucin 5AC (MUC5AC) have reported utility for differentiating cholangiocarcinoma (CCA) from benign biliary disease. Herein, serum levels of these markers were tested in 66 cases of CCA and 62 cases of primary sclerosing cholangitis (PSC) and compared with markers of liver function and inflammation. Markers panels were assessed for their ability to discriminate malignant and benign disease. Several of the markers were also assessed in pre-diagnosis biliary tract cancer (BTC) samples with performances evaluated at different times prior to diagnosis. We show that LRG1 and IL6 were unable to accurately distinguish CCA from PSC, whereas CA19-9, PKM2, CYFRA21.1 and MUC5AC were significantly elevated in malignancy. Area under the receiver operating characteristic curves for these individual markers ranged from 0.73–0.84, with the best single marker (PKM2) providing 61% sensitivity at 90% specificity. A panel combining PKM2, CYFRA21.1 and MUC5AC gave 76% sensitivity at 90% specificity, which increased to 82% sensitivity by adding gamma-glutamyltransferase (GGT). In the pre-diagnosis setting, LRG1, IL6 and PKM2 were poor predictors of BTC, whilst CA19-9 and C-reactive protein were elevated up to 2 years before diagnosis. In conclusion, LRG1, IL6 and PKM2 were not useful for early detection of BTC, whilst a model combining PKM2, CYFRA21.1, MUC5AC and GGT was beneficial in differentiating malignant from benign biliary disease, warranting validation in a prospective trial

An Economic Evaluation of Venous Thromboembolism Prophylaxis Strategies in Critically Ill Trauma Patients at Risk of Bleeding

Using decision analysis, Henry Stelfox and colleagues estimate the cost-effectiveness of three venous thromboembolism prophylaxis strategies in patients with severe traumatic injuries who were also at risk for bleeding complications

Physical activity, hormone replacement therapy, and insulin resistant coronary artery disease risk factors in postmenopausal women

Low physical activity levels and high serum C-reactive protein (CRP) levels are risk factors for coronary artery disease (CAD) in both men and women. However, postmenopausal women who take hormone replacement therapy (HRT) may have increased risk of CAD because of HRT-related increases in serum CRP. There are two manuscripts in this dissertation. The purpose of the first manuscript was to determine whether higher physical activity energy expenditure was associated with lower serum CRP, independent of oral HRT status and body fatness, in 133 postmenopausal women. Higher physical activity energy expenditures were significantly associated with lower serum CRP levels (r=-0.21, p=0.0l9), independent of oral HRT use, age, smoking behavior, alcohol consumption, aspirin use, and statin use. However, in the complete multivariate model, which included body fat, the association between higher physical activity and lower serum CRP levels was abolished. The purpose of the second study was to quantify the biological variability of insulin resistant CAD risk factors in a sample of 8 postmenopausal women. Risk factor outcomes, including serum total cholesterol, serum triglycerides (TG), serum high-density lipoprotein cholesterol (HDL-C), serum glucose, plasma insulin, serum CRP, waist and hip circumferences, abdominal sagittal diameter, body fat, systolic (SBP) and diastolic blood pressure, and self-reported physical activity energy expenditure, were measured on two occasions, 7-12 days apart. High absolute biological variability values (by standard error of measurement) were observed for serum TG (32.0 mg/dl), serum CRP (5.6 mg/l), SBP (4.0 mmHg), and physical activity (9.4 kcal/kg/week). High relative biological variability (by within-subjects coefficient of variation ≥27.3%) was also observed for serum TG, serum CRP, and physical activity. Bland-Altman plots identified individual outliers for serum TG, serum CRP, plasma insulin, and SBP. Together, the results suggest that the correlations between lower levels of serum CRP and higher levels of physical activity, though significant, may have been attenuated by the high biological variability of both serum CRP and physical activity. Thus, the importance of higher levels of physical activity, in decreasing serum CRP and the concomitant risk of heart disease, may be underestimated in the absence of serial measurement of serum CRP and physical activity

Безотходное использование углей

В работе сравниваются расчетная и аналитическая зольность отходов углеобогащения. Рассматриваются возможные пути и необходимость в сокращении отходов использования угля. Предложена модель безотходного использования углей.In this work the calculated and analytical ash contents of coal enrichment waste are compared. Possible ways and necessity in reducing coal waste are studied. The model for the non-waste use of coals is proposed

The effects of nocturnal hemodialysis compared to conventional hemodialysis on change in left ventricular mass: Rationale and study design of a randomized controlled pilot study

BACKGROUND: Nocturnal hemodialysis (NHD) is an alternative to conventional three times per week hemodialysis (CvHD) and has been reported to improve several health outcomes. To date, no randomized controlled trial (RCT) has compared NHD and CvHD. We have undertaken a multi-center RCT in hemodialysis patients comparing the effect of NHD to CvHD on left ventricular (LV) mass, as measured by cardiac magnetic resonance imaging (cMR). METHODOLOGY/DESIGN: All patients in Alberta, Canada, expressing an interest in performing NHD are eligible for the study. Patients enrolled in the study will be randomized to either NHD or CvHD for a six month period. All patients will have a full clinical assessment, including collection of biochemical and cMR data at baseline and at 6 months. Both groups of patients will be monitored biweekly to optimize blood pressure (BP) to a goal of <130/80 mmHg post-dialysis using a predefined BP management protocol. The primary outcome is change in LV mass, a surrogate marker for cardiac mortality, measured at baseline and 6 months. The high sensitivity and reproducibility of cMR facilitates reduction of the required sample size and the time needed between measures compared with echocardiography. Secondary outcomes include BP control, anemia, mineral metabolism, health-related quality of life, and costs. DISCUSSION: To our knowledge, this study will be the first RCT evaluating health outcomes in NHD. The impact of NHD on LV mass represents a clinically important outcome which will further elucidate the potential benefits of NHD and guide future clinical endpoint studies

Changes in monkey crystalline lens spherical aberration during simulated accommodation in a lens stretcher

8 págs.; 7 figs.; 2 apps.© 2015 The Association for Research in Vision and Ophthalmology, Inc. PURPOSE. The purpose of this study was to quantify accommodation-induced changes in the spherical aberration of cynomolgus monkey lenses. METHODS. Twenty-four lenses from 20 cynomolgus monkeys (Macaca fascicularis; 4.4-16.0 years of age; postmortem time 13.5±13.0 hours) were mounted in a lens stretcher. Lens spherical aberration was measured in the unstretched (accommodated) and stretched (relaxed) states with a laser ray tracing system that delivered 51 equally spaced parallel rays along 1 meridian of the lens over the central 6-mm optical zone. A camera mounted below the lens was used to measure the ray height at multiple positions along the optical axis. For each entrance ray, the change in ray height with axial position was fitted with a third-order polynomial. The effective paraxial focal length and Zernike spherical aberration coefficients corresponding to a 6-mm pupil diameter were extracted from the fitted values. RESULTS. The unstretched lens power decreased with age from 59.3±6 4.0 diopters (D) for young lenses to 45.7±6 3.1 D for older lenses. The unstretched lens shifted toward less negative spherical aberration with age, from -6.3±0.7 lm for young lenses to-5.0±0.5 lm for older lenses. The power and spherical aberration of lenses in the stretched state were independent of age, with values of 33.5±6 3.4 D and-2.6±0.5 lm, respectively. CONCLUSIONS. Spherical aberration is negative in cynomolgus monkey lenses and becomes more negative with accommodation. These results are in good agreement with the predicted values using computational ray tracing in a lens model with a reconstructed gradient refractive index. The spherical aberration of the unstretched lens becomes less negative with age.Supported by National Institutes of Health Grants R01EY14225, R01EY021834, and F31EY021444 Ruth L. Kirschstein National Research Service Award individual predoctoral fellowship [BM]), and center Grant P30EY14801; Australian government Cooperative Research Centre Scheme (Vision CRC); Florida Lions Eye Bank; Karl R. Olsen and Martha E. Hildebrandt; an unrestricted grant from Research to Prevent Blindness; Henri and Flore Lesieur Foundation (JMP); Spanish government Grant FIS2011-25637; and European Research Council Grants ERC-2011-AdG-294099 and CSIC i-LINKþ0609Peer Reviewe

Prediction of residual stresses in girth welded pipes using an artificial neural network approach

Management of operating nuclear power plants greatly relies on structural integrity assessments for safety critical pressure vessels and piping components. In the present work, residual stress profiles of girth welded austenitic stainless steel pipes are characterised using an artificial neural network approach. The network has been trained using residual stress data acquired from experimental measurements found in literature. The neural network predictions are validated using experimental measurements undertaken using neutron diffraction and the contour method. The approach can be used to predict through-wall distribution of residual stresses over a wide range of pipe geometries and welding parameters thereby finding potential applications in structural integrity assessment of austenitic stainless steel girth welds

The pseudokinase MLKL mediates programmed hepatocellular necrosis independently of RIPK3 during hepatitis

Although necrosis and necroinflammation are central features of many liver diseases, the role of programmed necrosis in the context of inflammation-dependent hepatocellular death remains to be fully determined. Here, we have demonstrated that the pseudokinase mixed lineage kinase domain-like protein (MLKL), which plays a key role in the execution of receptor interacting protein (RIP) lcinase-dependent necroptosis, is upregulated and activated in human autoimmune hepatitis and in a murine model of inflammation-dependent hepatitis. Using genetic and pharmacologic approaches, we determined that hepatocellular necrosis in experimental hepatitis is driven by an MLKL-dependent pathway that occurs independently of RIPK3. Moreover, we have provided evidence that the cytotoxic activity of the proinflammatory cytokine IFN-gamma in hepatic inflammation is strongly connected to induction of MLKL expression via activation of the transcription factor STAT1. In summary, our results reveal a pathway for MLKL-dependent programmed necrosis that is executed in the absence of RIPK3 and potentially drives the pathogenesis of severe liver diseases