Subpopulations of liver coated vesicles resolved by preparative agarose gel electrophoresis.

Rat liver clathrin coated vesicles (CVs) were separated into several distinct subpopulations using non-sieving concentrations of agarose, which allowed the separation of species differing primarily in surface charge. Using preparative agarose electrophoresis (Kedersha, N. L., and L. H. Rome, 1986, Anal. Biochem., in press), the CVs were recovered and analyzed for differences in morphology, coat protein composition, and stripped vesicle protein composition. Coat proteins from different populations appeared identical on SDS PAGE, and triskelions stripped from the different populations showed the same mobility on the agarose gel, suggesting that the mobility differences observed in intact CVs were due to differences in the surface charge of underlying vesicles rather than to variations in their clathrin coats. Several non-coat polypeptides appeared to segregate exclusively with different populations as resolved by two-dimensional electrophoresis. Stripped CVs also exhibited considerable heterogeneity when analyzed by Western blotting: the fast-migrating population was enriched in the mannose 6-phosphate receptor, secretory acetylcholine esterase, and an Mr 195,000 glycoprotein. The slow-migrating population of CVs was enriched in the asialoglycoprotein receptor, and it appeared to contain all detectable concanavalin A-binding polypeptides as well as the bulk of detectable WGA-binding proteins. When CVs were prepared from 125I-asialoorosomucoid-perfused rat liver, ligand was found in the slow-migrating CVs, suggesting that these were endocytic in origin. Morphological differences were also observed: the fast-migrating population was enriched in smaller CVs, whereas the slow-migrating population exhibited an enrichment in larger CVs. As liver consists largely of hepatocytes, these subpopulations appear to originate from the same cell type and probably represent CVs of different intracellular origin and destination

A semi-Markov model for stroke with piecewise-constant hazards in the presence of left, right and interval censoring.

This paper presents a parametric method of fitting semi-Markov models with piecewise-constant hazards in the presence of left, right and interval censoring. We investigate transition intensities in a three-state illness-death model with no recovery. We relax the Markov assumption by adjusting the intensity for the transition from state 2 (illness) to state 3 (death) for the time spent in state 2 through a time-varying covariate. This involves the exact time of the transition from state 1 (healthy) to state 2. When the data are subject to left or interval censoring, this time is unknown. In the estimation of the likelihood, we take into account interval censoring by integrating out all possible times for the transition from state 1 to state 2. For left censoring, we use an Expectation-Maximisation inspired algorithm. A simulation study reflects the performance of the method. The proposed combination of statistical procedures provides great flexibility. We illustrate the method in an application by using data on stroke onset for the older population from the UK Medical Research Council Cognitive Function and Ageing Study

Assessing the Risk of Metals and Their Mixtures in the Antarctic Nearshore Marine Environment with Diffusive Gradients in Thin-Films

© 2019 American Chemical Society. Robust environmental assessments and contaminant monitoring in Antarctic near-shore marine environments need new techniques to overcome challenges presented by a highly dynamic environment. This study outlines an approach for contaminant monitoring and risk assessment in Antarctic marine conditions using diffusive gradients in thin-films (DGT) coupled to regionally specific ecotoxicology data and environmental quality standards. This is demonstrated in a field study where DGT samplers were deployed in the near-shore marine environment of East Antarctica around the operational Casey station and the abandoned Wilkes station to measure the time-averaged biologically available fraction of metal contaminants. The incorporation of DGT-labile concentrations to reference toxicity mixture models for three Antarctic organisms predicted low toxic effects (<5% effect to the growth or development of each organism). The comparison of metal concentrations to the Australian and New Zealand default water quality guideline values (WQGVs) showed no marine site exceeding the WQGVs for 95% species protection. However, all sites exceeded the 99% WQGVs due to copper concentrations that are likely of geogenic origin (i.e., not from anthropogenic sources). This study provides evidence supporting the use of the DGT technique to monitor contaminants and assess their environmental risk in the near-shore marine environment of Antarctica

Doses of neighborhood nature: the benefits for mental health of living with nature

This is the author accepted manuscript. The final version is available from OUP via the DOI in this record.Experiences of nature provide many mental health benefits, particularly for people living in urban areas. The natural characteristics of city residents’ neighborhoods are likely to be critical determinants of the daily nature dose that they receive, however which characteristics are important remains unclear. One possibility is that the greatest benefits are provided by characteristics that are most visible during the day and so most likely to be experienced by people. We demonstrate that of five neighborhood nature characteristics tested, vegetation cover and afternoon bird abundances were positively associated with a lower prevalence of depression, anxiety and stress. Further, dose-response modelling shows a threshold response where the population prevalence of mental health issues is significantly lower beyond minimum limits of neighborhood vegetation cover (depression >20% cover, anxiety >30% cover, stress >20% cover). Our findings demonstrate quantifiable associations of mental health with the characteristics of nearby nature that people actually experience

A comparison of course-related stressors in undergraduate problem-based learning (PBL) versus non-PBL medical programmes

Background: Medical students report high levels of stress related to their medical training as well as to other personal and financial factors. The aim of this study is to investigate whether there are differences in course-related stressors reported by medical students on undergraduate problem-based learning (PBL) and non-PBL programmes in the UK. Method: A cross-sectional study of second-year medical students in two UK medical schools (one PBL and one non-PBL programme) was conducted. A 16-question self-report questionnaire, derived from the Perceived Medical Student Stress Scale and the Higher Education Stress Inventory, was used to measure course-related stressors. Following univariate analysis of each stressor between groups, multivariate logistic regression was used to determine which stressors were the best predictors of each course type, while controlling for socio-demographic differences between the groups. Results: A total of 280 students responded. Compared to the non-PBL students (N = 197), the PBL students (N = 83) were significantly more likely to agree that: they did not know what the faculty expected of them (Odds Ratio (OR) = 0.38, p = 0.03); there were too many small group sessions facilitated only by students resulting in an unclear curriculum (OR = 0.04, p < 0.0001); and that there was a lack of opportunity to explore academic subjects of interest (OR = 0.40, p = 0.02). They were significantly more likely to disagree that: there was a lack of encouragement from teachers (OR = 3.11, p = 0.02); and that the medical course fostered a sense of anonymity and feelings of isolation amongst students (OR = 3.42, p = 0.008). Conclusion: There are significant differences in the perceived course-related stressors affecting medical students on PBL and non-PBL programmes. Course designers and student support services should therefore tailor their work to minimise, or help students cope with, the specific stressors on each course type to ensure optimum learning and wellbeing among our future doctors

Primary pyogenic spondylitis following kyphoplasty: a case report

<p>Abstract</p> <p>Introduction</p> <p>Only ten cases of primary pyogenic spondylitis following vertebroplasty have been reported in the literature. To the best of our knowledge, we present the first reported case of primary pyogenic spondylitis and spondylodiscitis caused by kyphoplasty.</p> <p>Case presentation</p> <p>A 72-year old Caucasian man with an osteoporotic compression fracture of the first lumbar vertebra after kyphoplasty developed sensory incomplete paraplegia below the first lumbar vertebra. This was caused by myelon compression following pyogenic spondylitis with a psoas abscess. Computed tomography guided aspiration of the abscess cavity yielded group C <it>Streptococcus</it>. The psoas abscess was percutaneously drained and laminectomy and posterior instrumentation with an internal fixator from the eleventh thoracic vertebra to the fourth lumbar vertebra was performed. In a second operation, corpectomy of the first lumbar vertebra with cement removal and fusion from the twelfth thoracic vertebra to the second lumbar vertebra with a titanium cage was performed. Six weeks postoperatively, the patient was pain free with no neurologic deficits or signs of infection.</p> <p>Conclusion</p> <p>Pyogenic spondylitis is an extremely rare complication after kyphoplasty. When these patients develop recurrent back pain postoperatively, the diagnosis of pyogenic spondylitis must be considered.</p

Computerized ICU Data Management Pitfalls and Promises

journal articleBiomedical Informatic

Impacts on terrestrial biodiversity of moving from a 2ᵒC to a 1.5ᵒC target

We applied a recently developed tool to examine the reduction in climate risk to biodiversity in moving from a 2°C to a 1.5°C target. We then reviewed the recent literature examining the impact of (a) land-based mitigation options and (b) land-based greenhouse gas removal options on biodiversity. We show that holding warming to 1.5°C versus 2°C can significantly reduce the number of species facing a potential loss of 50% of their climatic range. Further, there would be an increase of 5.5–14% of the globe that could potentially act as climatic refugia for plants and animals, an area equivalent to the current global protected area network. Efforts to meet the 1.5°C target through mitigation could largely be consistent with biodiversity protection/enhancement. For impacts of land-based greenhouse gas removal technologies on biodiversity, some (e.g. soil carbon sequestration) could be neutral or positive, others (e.g. bioenergy with carbon capture and storage) are likely to lead to conflicts, while still others (e.g. afforestation/reforestation) are context-specific, when applied at scales necessary for meaningful greenhouse gas removal. Additional effort to meet the 1.5°C target presents some risks, particularly if inappropriately managed, but it also presents opportunities. This article is part of the theme issue ‘The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'

Phase preserving amplification near the quantum limit with a Josephson Ring Modulator

Recent progress in solid state quantum information processing has stimulated the search for ultra-low-noise amplifiers and frequency converters in the microwave frequency range, which could attain the ultimate limit imposed by quantum mechanics. In this article, we report the first realization of an intrinsically phase-preserving, non-degenerate superconducting parametric amplifier, a so far missing component. It is based on the Josephson ring modulator, which consists of four junctions in a Wheatstone bridge configuration. The device symmetry greatly enhances the purity of the amplification process and simplifies both its operation and analysis. The measured characteristics of the amplifier in terms of gain and bandwidth are in good agreement with analytical predictions. Using a newly developed noise source, we also show that our device operates within a factor of three of the quantum limit. This development opens new applications in the area of quantum analog signal processing