Biomechanical Characterization of Endothelial Cells Exposed to Shear Stress Using Acoustic Force Spectroscopy.

Characterizing mechanical properties of cells is important for understanding many cellular processes, such as cell movement, shape, and growth, as well as adaptation to changing environments. In this study, we explore the mechanical properties of endothelial cells that form the biological barrier lining blood vessels, whose dysfunction leads to development of many cardiovascular disorders. Stiffness of living endothelial cells was determined by Acoustic Force Spectroscopy (AFS), by pull parallel multiple functionalized microspheres located at the cell-cell periphery. The unique configuration of the acoustic microfluidic channel allowed us to develop a long-term dynamic culture protocol exposing cells to laminar flow for up to 48 h, with shear stresses in the physiological range (i.e., 6 dyn/cm2). Two different Endothelial cells lines, Human Aortic Endothelial Cells (HAECs) and Human Umbilical Vein Endothelial Cells (HUVECs), were investigated to show the potential of this tool to capture the change in cellular mechanical properties during maturation of a confluent endothelial monolayer. Immunofluorescence microscopy was exploited to follow actin filament rearrangement and junction formation over time. For both cell types we found that the application of shear-stress promotes the typical phenotype of a mature endothelium expressing a linear pattern of VE-cadherin at the cell-cell border and actin filament rearrangement along the perimeter of Endothelial cells. A staircase-like sequence of increasing force steps, ranging from 186 pN to 3.5 nN, was then applied in a single measurement revealing the force-dependent apparent stiffness of the membrane cortex in the kPa range. We also found that beads attached to cells cultured under dynamic conditions were harder to displace than cells cultured under static conditions, showing a stiffer membrane cortex at cell periphery. All together these results demonstrate that the AFS can identify changes in cell mechanics based on force measurements of adherent cells under conditions mimicking their native microenvironment, thus revealing the shear stress dependence of the mechanical properties of neighboring endothelial cells

Triage for coronary artery bypass graft surgery in Canada: Do patients agree on who should come first?

<p>Abstract</p> <p>Background</p> <p>The extent to which clinical and non-clinical factors impact on the waiting-list prioritization preferences of patients in the queue is unknown. Using a series of hypothetical scenarios, the objective of this study was to examine the extent to which clinical and non-clinical factors impacted on how patients would prioritize others relative to themselves in the coronary artery bypass surgical queue.</p> <p>Methods</p> <p>Ninety-one consecutive eligible patients awaiting coronary artery bypass grafting surgery at Sunnybrook Health Sciences Centre (median waiting-time duration prior to survey of 8 weeks) were given a self-administered survey consisting of nine scenarios in which clinical and non-clinical characteristic profiles of hypothetical patients (also awaiting coronary artery bypass surgery) were varied. For each scenario, patients were asked where in the queue such hypothetical patients should be placed relative to themselves.</p> <p>Results</p> <p>The eligible response rate was 65% (59/91). Most respondents put themselves marginally ahead of a hypothetical patient with identical clinical and non-clinical characteristics as themselves. There was a strong tendency for respondents to place patients of higher clinical acuity ahead of themselves in the queue (P < 0.0001). Social independence among young individuals was a positively valued attribute (P < 0.0001), but neither age per se nor financial status, directly impacted on patients waiting-list priority preferences.</p> <p>Conclusion</p> <p>While patient perceptions generally reaffirmed a bypass surgical triage process based on principals of equity and clinical acuity, the valuation of social independence may justify further debate with regard to the inclusion of non-clinical factors in waiting-list prioritization management systems in Canada, as elsewhere.</p

Historical Criminology and the Explanatory Power of the Past

To what extent can the past ‘explain’ the present? This deceptively simple question lies at the heart of historical criminology (research which incorporates historical primary sources while addressing present-day debates and practices in the criminal justice field). This article seeks first to categorise the ways in which criminologists have used historical data thus far, arguing that it is most commonly deployed to ‘problematize’ the contemporary rather than to ‘explain’ it. The article then interrogates the reticence of criminologists to attribute explicative power in relation to the present to historical data. Finally, it proposes the adoption of long time-frame historical research methods, outlining three advantages which would accrue from this: the identification and analysis of historical continuities; a more nuanced, shared understanding of micro/macro change over time in relation to criminal justice; and a method for identifying and analysing instances of historical recurrence, particularly in perceptions and discourses around crime and justice

Towards quantifying uncertainty in predictions of Amazon 'dieback'.

This is the final version of the article. It first appeared from The Royal Society via http://dx.doi.org/10.1098/rstb.2007.0028Simulations with the Hadley Centre general circulation model (HadCM3), including carbon cycle model and forced by a 'business-as-usual' emissions scenario, predict a rapid loss of Amazonian rainforest from the middle of this century onwards. The robustness of this projection to both uncertainty in physical climate drivers and the formulation of the land surface scheme is investigated. We analyse how the modelled vegetation cover in Amazonia responds to (i) uncertainty in the parameters specified in the atmosphere component of HadCM3 and their associated influence on predicted surface climate. We then enhance the land surface description and (ii) implement a multilayer canopy light interception model and compare with the simple 'big-leaf' approach used in the original simulations. Finally, (iii) we investigate the effect of changing the method of simulating vegetation dynamics from an area-based model (TRIFFID) to a more complex size- and age-structured approximation of an individual-based model (ecosystem demography). We find that the loss of Amazonian rainforest is robust across the climate uncertainty explored by perturbed physics simulations covering a wide range of global climate sensitivity. The introduction of the refined light interception model leads to an increase in simulated gross plant carbon uptake for the present day, but, with altered respiration, the net effect is a decrease in net primary productivity. However, this does not significantly affect the carbon loss from vegetation and soil as a consequence of future simulated depletion in soil moisture; the Amazon forest is still lost. The introduction of the more sophisticated dynamic vegetation model reduces but does not halt the rate of forest dieback. The potential for human-induced climate change to trigger the loss of Amazon rainforest appears robust within the context of the uncertainties explored in this paper. Some further uncertainties should be explored, particularly with respect to the representation of rooting depth

Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1

PMCID: PMC3601088This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Personal health promotion at US medical schools: a quantitative study and qualitative description of deans' and students' perceptions

BACKGROUND: Prior literature has shown that physicians with healthy personal habits are more likely to encourage patients to adopt similar habits. However, despite the possibility that promoting medical student health might therefore efficiently improve patient outcomes, no one has studied whether such promotion happens in medical school. We therefore wished to describe both typical and outstanding personal health promotion environments experienced by students in U.S. medical schools. METHODS: We collected information through four different modalities: a literature review, written surveys of medical school deans and students, student and dean focus groups, and site visits at and interviews with medical schools with reportedly outstanding student health promotion programs. RESULTS: We found strong correlations between deans' and students' perceptions of their schools' health promotion environments, including consistent support of the idea of schools' encouraging healthy student behaviors, with less consistent follow-through by schools on this concept. Though students seemed to have thought little about the relationships between their own personal and clinical health promotion practices, deans felt strongly that faculty members should model healthy behaviors. CONCLUSIONS: Deans' support of the relationship between physicians' personal and clinical health practices, and concern about their institutions' acting on this relationship augurs well for the role of student health promotion in the future of medical education. Deans seem to understand their students' health environment, and believe it could and should be improved; if this is acted on, it could create important positive changes in medical education and in disease prevention

A spatial emergent constraint on the sensitivity of soil carbon turnover to global warming (article)

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: The datasets analysed during this study are available online: CMIP5 model output [https://esgf-node.llnl.gov/search/CMIP5/], CMIP6 model output [https://esgf-node.llnl.gov/search/cmip6/], The WFDEI Meteorological Forcing Data [https://rda.ucar.edu/datasets/ds314.2/], CARDAMOM Heterotrophic Respiration [https://datashare.is.ed.ac.uk/handle/10283/875], MODIS Net Primary Production [https://lpdaac.usgs.gov/products/mod17a3v055/], Raich et al. 2002 Soil Respiration [https://cdiac.ess-dive.lbl.gov/epubs/ndp/ndp081/ndp081.html], Hashimoto et al. 2015 Heterotrophic Respiration [http://cse.ffpri.affrc.go.jp/shojih/data/index.html], and the datasets for observational Soil Carbon [https://github.com/rebeccamayvarney/soiltau_ec].Code availability: The Python code used to complete the analysis and produce the figures in this study is available in the following online repository [https://github.com/rebeccamayvarney/soiltau_ec].Carbon cycle feedbacks represent large uncertainties in climate change projections, and the response of soil carbon to climate change contributes the greatest uncertainty to this. Future changes in soil carbon depend on changes in litter and root inputs from plants and especially on reductions in the turnover time of soil carbon (τs) with warming. An approximation to the latter term for the top one metre of soil (ΔCs,τ) can be diagnosed from projections made with the CMIP6 and CMIP5 Earth System Models (ESMs), and is found to span a large range even at 2 °C of global warming (-196 ± 117 PgC). Here, we present a constraint on ΔCs,τ, which makes use of current heterotrophic respiration and the spatial variability of τs inferred from observations. This spatial emergent constraint allows us to halve the uncertainty in ΔCs,τ at 2 °C to -232 ± 52 PgC

Which circulating antioxidant vitamins are confounded by socioeconomic deprivation? The MIDSPAN family study

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Antioxidant vitamins are often described as having “independent” associations with risk of cancer, cardiovascular disease (CVD) and mortality. We aimed to compare to what extent a range of antioxidant vitamins and carotenoids are associated with adulthood and childhood markers of socioeconomic deprivation and to adverse lifestyle factors.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and Findings:&lt;/b&gt; Socioeconomic and lifestyle measures were available in 1040 men and 1298 women from the MIDSPAN Family Study (30–59 years at baseline) together with circulating levels of vitamins A, C, E, and carotenoids (α-carotene, β-carotene, lutein and lycopene). Markers of socioeconomic deprivation in adulthood were consistently as strongly associated with lower vitamin C and carotenoid levels as markers of adverse lifestyle; the inverse association with overcrowding was particularly consistent (vitamin C and carotenoids range from 19.1% [95% CI 30.3–6.0] to 38.8% [49.9–25.3] lower among those in overcrowded residencies). These associations were consistent after adjusting for month, classical CVD risk factors, body mass index, physical activity, vitamin supplements, dietary fat and fibre intake. Similar, but weaker, associations were seen for childhood markers of deprivation. The association of vitamin A or E were strikingly different; several adult adverse lifestyle factors associated with higher levels of vitamin A and E, including high alcohol intake for vitamin A (9.5% [5.7–13.5]) and waist hip ratio for vitamin E (9.5% [4.8–14.4]), with the latter associations partially explained by classical risk factors, particularly cholesterol levels.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Plasma vitamin C and carotenoids have strong inverse associations with adulthood markers of social deprivation, whereas vitamin A and E appear positively related to specific adverse lifestyle factors. These findings should help researchers better contextualize blood antioxidant vitamin levels by illustrating the potential limitations associated with making causal inferences without consideration of social deprivation.&lt;/p&gt