Imaging of changes in copper trafficking and redistribution in a mouse model of Niemann-Pick C disease using positron emission tomography

Niemann-Pick C disease (NPC) is an autosomal recessive lysosomal storage disorder resulting from mutations in the NPC1 (95% of cases) or NPC2 genes. Disturbance of copper homeostasis has been reported in NPC1 disease.In this study we have used whole-body positron emission tomography (PET) and brain electronic autoradiography with copper-64 (64Cu), in the form of the copper(II) bis(thiosemicarbazonato) complex 64Cu-GTSM, to imageshort-term changes in copper trafficking after intravenous injection in a transgenic mouse model of NPC1 disease. 64Cu-GTSM is taken up in all tissues and dissociates rapidly inside cells, allowing monitoring of the subsequentefflux and redistribution of 64Cu from all tissues. Significantly enhanced retention of 64Cu radioactivity was observed in brain, lungs and blood at 15 h post-injection in symptomatic Npc1-/- transgenic mice compared towildtype controls. The enhanced retention of 64Cu in brain was confirmed by electronic autoradiography, particularly in the midbrain, thalamus, medulla and pons regions. PET imaging with 64Cu in selected chemical forms could be a useful diagnostic and research tool for the management and understanding of NPC1 disease

A Quality Metric for Visualization of Clusters in Graphs

Traditionally, graph quality metrics focus on readability, but recent studies show the need for metrics which are more specific to the discovery of patterns in graphs. Cluster analysis is a popular task within graph analysis, yet there is no metric yet explicitly quantifying how well a drawing of a graph represents its cluster structure. We define a clustering quality metric measuring how well a node-link drawing of a graph represents the clusters contained in the graph. Experiments with deforming graph drawings verify that our metric effectively captures variations in the visual cluster quality of graph drawings. We then use our metric to examine how well different graph drawing algorithms visualize cluster structures in various graphs; the results con-firm that some algorithms which have been specifically designed to show cluster structures perform better than other algorithms.Comment: Appears in the Proceedings of the 27th International Symposium on Graph Drawing and Network Visualization (GD 2019

Matching a community assessment tool to the requirements of practice

Over the last two decades, performance-based metrics have been applied in master planning as a means to estimate the impacts of large-scale development on the local and global environment. Community sustainability assessment has developed to provide a practical method for assessing the performance of a spatial master plan against an array of sustainability indicators. This paper considers the adequacy of such a tool to provide reliable information when and as required for decision-making in the planning process. It reviews Breeam (building research establishment environmental assessment method) Communities 2012 specifically examining whether this tool provides an analysis which is strategic, comprehensive and integrated. Breeam 2012 is found to be adequately comprehensive in the current operational context of the British planning system. The sustainability assessment model can usefully inform decision-making at the strategic ‘stage gates’ of master planning. However, the analytical methodology of the assessment model is inherently fractional. This complicates how a ‘balanced’ evaluation of the relative importance of sustainability issues is reached and agreed. It is suggested that a project culture of trans-disciplinary dialogue and explorative learning is required to promote the understanding and use of sustainability assessment practice in master planning

Despotism and Risk of Infanticide Influence Grizzly Bear Den-Site Selection

Given documented social dominance and intraspecific predation in bear populations, the ideal despotic distribution model and sex hypothesis of sexual segregation predict adult female grizzly bears (Ursus arctos) will avoid areas occupied by adult males to reduce risk of infanticide. Under ideal despotic distribution, juveniles should similarly avoid adult males to reduce predation risk. Den-site selection and use is an important component of grizzly bear ecology and may be influenced by multiple factors, including risk from conspecifics. To test the role of predation risk and the sex hypothesis of sexual segregation, we compared adult female (n = 142), adult male (n = 36), and juvenile (n = 35) den locations in Denali National Park and Preserve, Alaska, USA. We measured elevation, aspect, slope, and dominant land cover for each den site, and used maximum entropy modeling to determine which variables best predicted den sites. We identified the global model as the best-fitting model for adult female (area under curve (AUC) = 0.926) and elevation as the best predictive variable for adult male (AUC = 0.880) den sites. The model containing land cover and elevation best-predicted juvenile (AUC = 0.841) den sites. Adult females spatially segregated from adult males, with dens characterized by higher elevations ( = 1,412 m, SE = 52) and steeper slopes ( = 21.9°, SE = 1.1) than adult male (elevation:  = 1,209 m, SE = 76; slope:  = 15.6°, SE = 1.9) den sites. Juveniles used a broad range of landscape attributes but did not avoid adult male denning areas. Observed spatial segregation by adult females supports the sex hypothesis of sexual segregation and we suggest is a mechanism to reduce risk of infanticide. Den site selection of adult males is likely related to distribution of food resources during spring

Four consecutive yearly point-prevalence studies in Wales indicate lack of improvement in sepsis care on the wards

The ‘Sepsis Six’ bundle was promoted as a deliverable tool outside of the critical care settings, but there is very little data available on the progress and change of sepsis care outside the critical care environment in the UK. Our aim was to compare the yearly prevalence, outcome and the Sepsis Six bundle compliance in patients at risk of mortality from sepsis in non-intensive care environments. Patients with a National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled into four yearly 24-h point prevalence studies, carried out in fourteen hospitals across Wales from 2016 to 2019. We followed up patients to 30 days between 2016–2019 and to 90 days between 2017 and 2019. Out of the 26,947 patients screened 1651 fulfilled inclusion criteria and were recruited. The full ‘Sepsis Six’ care bundle was completed on 223 (14.0%) occasions, with no significant difference between the years. On 190 (11.5%) occasions none of the bundle elements were completed. There was no significant correlation between bundle element compliance, NEWS or year of study. One hundred and seventy (10.7%) patients were seen by critical care outreach; the ‘Sepsis Six’ bundle was completed significantly more often in this group (54/170, 32.0%) than for patients who were not reviewed by critical care outreach (168/1385, 11.6%; p < 0.0001). Overall survival to 30 days was 81.7% (1349/1651), with a mean survival time of 26.5 days (95% CI 26.1–26.9) with no difference between each year of study. 90-day survival for years 2017–2019 was 74.7% (949/1271), with no difference between the years. In multivariate regression we identified older age, heart failure, recent chemotherapy, higher frailty score and do not attempt cardiopulmonary resuscitation orders as significantly associated with increased 30-day mortality. Our data suggests that despite efforts to increase sepsis awareness within the NHS, there is poor compliance with the sepsis care bundles and no change in the high mortality over the study period. Further research is needed to determine which time-sensitive ward-based interventions can reduce mortality in patients with sepsis and how can these results be embedded to routine clinical practice

Market orientation, performance and the market environment : a study of Australian manufacturing SME's

This paper undertakes an analysis of a range of previous studies to explore the link between market orientation, performance and the competitive environment. This paper first reviews literature then presents the results of an empirical study of 73 Australian manufacturing firms located in Greater Western Sydney. From the analysis of the data, links are established between changes in a firm’s competitive environment and the resulting market orientation of respondent firms

Learning object-oriented programming in six hours: An experience with school students

Teaching object-oriented programming skills in six hours to school students who have either never programmed, or who have never encountered object-oriented programming before, is an ambitious task. Within these time and skill limitations, we devised an educational strategy based on learning through exercises, and trialled it with sixty students who attended a three day vacation school. The observations presented in this paper indicate that it is possible to give novices a worthwhile, enlightening and exciting programming experience within a restricted time period