Differing calcification processes in cultured vascular smooth muscle cells and osteoblasts

© 2019 Published by Elsevier Inc.Arterial medial calcification (AMC) is the deposition of calcium phosphate mineral, often as hydroxyapatite, inthe medial layer of the arteries. AMC shares some similarities to skeletal mineralisation and has been associatedwith the transdifferentiation of vascular smooth muscle cells (VSMCs) towards an osteoblast-like phenotype. Thisstudy used primary mouse VSMCs and calvarial osteoblasts to directly compare the established and widely usedin vitromodels of AMC and bone formation. Significant differences were identified between osteoblasts andcalcifying VSMCs. First, osteoblasts formed large mineralised bone nodules that were associated with widespreaddeposition of an extracellular collagenous matrix. In contrast, VSMCs formed small discrete regions of calcifi-cation that were not associated with collagen deposition and did not resemble bone. Second, calcifying VSMCsdisplayed a progressive reduction in cell viability over time (≤7-fold), with a 50% increase in apoptosis,whereas osteoblast and control VSMCs viability remained unchanged. Third, osteoblasts expressed high levels ofalkaline phosphatase (TNAP) activity and TNAP inhibition reduced bone formation by to 90%. TNAP activity incalcifying VSMCs was∼100-fold lower than that of bone-forming osteoblasts and cultures treated withβ-gly-cerophosphate, a TNAP substrate, did not calcify. Furthermore, TNAP inhibition had no effect on VSMC calci-fication. Although, VSMC calcification was associated with increased mRNA expression of osteoblast-relatedgenes (e.g. Runx2, osterix, osteocalcin, osteopontin), the relative expression of these genes was up to 40-foldlower in calcifying VSMCs versus bone-forming osteoblasts. In summary, calcifying VSMCsin vitrodisplay somelimited osteoblast-like characteristics but also differ in several key respects: 1) their inability to form collagen-containing bone; 2) their lack of reliance on TNAP to promote mineral deposition; and, 3) the deleterious effectof calcification on their viability.Peer reviewedFinal Published versio

Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial)

Introduction: Several observational studies suggest that statins modulate the pathophysiology of sepsis and may prevent its progression. The aim of this study was to determine if the acute administration of atorvastatin reduces sepsis progression in statin naïve patients hospitalized with sepsis. Methods: A single centre phase II randomized double-blind placebo-controlled trial. Patients with sepsis were randomized to atorvastatin 40 mg daily or placebo for the duration of their hospital stay up to a maximum of 28-days. The primary end-point was the rate of sepsis progressing to severe sepsis during hospitalization. Results: 100 patients were randomized, 49 to the treatment with atorvastatin and 51 to placebo. Patients in the atorvastatin group had a significantly lower conversion rate to severe sepsis compared to placebo (4% vs. 24% p = 0.007.), with a number needed to treat of 5. No significant difference in length of hospital stay, critical care unit admissions, 28-day and 12-month readmissions or mortality was observed. Plasma cholesterol and albumin creatinine ratios were significantly lower at day 4 in the atorvastatin group (p < 0.0001 and p = 0.049 respectively). No difference in adverse events between the two groups was observed (p = 0.238). Conclusions: Acute administration of atorvastatin in patients with sepsis may prevent sepsis progression. Further multi-centre trials are required to verify these findings. Trial Registration: International Standard Randomized Control Trial Registry ISRCTN64637517

Early intervention for stigma towards mental illness? Promoting positive attitudes towards severe mental illness in primary school children

Purpose Stigma towards severe mental illness (SMI) is widespread, exacerbating mental health problems, and impacting on help-seeking and social inclusion. Anti-stigma campaigns are meeting with success, but results are mixed. Earlier intervention to promote positive mental health literacy rather than challenge stigma, may show promise, but little is known about stigma development or interventions in younger children. This study will investigate (i) children’s knowledge, attitudes and behaviour towards SMI and (ii) whether we can positively influence children’s attitudes before stigma develops. Design/methodology/approach A cross sectional study investigated mental health schema in 7-11 year olds. An experimental intervention investigated whether an indirect contact story-based intervention in 7-8 year olds led to more positive mental health schema. Findings: Young children’s schema were initially positive, and influenced by knowledge and contact with mental illness & intergroup anxiety, but were more stigmatising in older girls as intergroup anxiety increased. The indirect contact intervention was effective in promoting positive mental health schema, partially mediated by knowledge. Social Implications: Intervening early to shape concepts of mental illness more positively, as they develop in young children, may represent a more effective strategy than attempting to challenge and change mental health stigma once it has formed in adolescents and adults. Originality/Value: This study is the first to investigate an intervention targeted at the prevention of stigma towards severe mental illness, in young children, at the point that stigma is emerging

Carbon exchange between a shelf sea and the ocean: The Hebrides Shelf, west of Scotland

Global mass balance calculations indicate the majority of particulate organic carbon (POC) exported from shelf seas is transferred via downslope exchange processes. Here we demonstrate the downslope flux of POC from the Hebrides Shelf is approximately 3-to-5-fold larger per unit length/area than the global mean. To reach this conclusion we quantified the offshore transport of particulate and dissolved carbon fractions via the “Ekman Drain”, a strong downwelling feature of the NW European Shelf circulation, and subsequently compared these fluxes to simultaneous regional air-sea CO2 fluxes and on-shore wind-driven Ekman fluxes to constrain the carbon dynamics of this shelf. Along the shelf break we estimate a mean offshelf total carbon (dissolved?+?particulate) flux of 4.2 tonnes C m?1 d?1 compared to an onshelf flux of 4.5 tonnes C m?1 d?1. Organic carbon represented 3.3% of the onshelf carbon flux but 6.4% of the offshelf flux indicating net organic carbon export. Dissolved organic carbon represented 95% and POC 5% of the exported organic carbon pool. When scaled along the shelf break the total offshelf POC flux (0.007 Tg C d?1) was found to be three times larger than the regional air-sea CO2 ingassing flux (0.0021 Tg C d?1), an order of magnitude larger than the particulate inorganic carbon flux (0.0003 Tg C d?1) but far smaller than the DIC (2.03 Tg C d?1) or DOC (0.13 Tg C d?1) fluxes. Significant spatial heterogeneity in the Ekman drain transport confirms that offshelf carbon fluxes via this mechanism are also spatially heterogeneous. This article is protected by copyright. All rights reserved

Scales of analysis : evidence of fish and fish processing at Star Carr

This contribution directly relates to the paper published by Wheeler in 1978 entitled ‘Why were there no fish re- mains at Star Carr?’. Star Carr is arguably the richest, most studied and re-interpreted Mesolithic site in Europe but the lack of fish remains has continued to vex scholars. Judging from other materials, the preservation conditions at the site in the late 1940s/early 1950s should have been good enough to permit the survival of fish remains, and particularly dentaries of the northern pike (Esox lucius L., 1758) as found on other European sites of this age. The lack of evidence has therefore been attributed to a paucity of fish in the lake. However, new research has provided multiple lines of evidence, which not only demonstrate the presence of fish, but also provide evidence for the species present, data on how and where fish were being processed on site, and interpretations for the fishing methods that might have been used. This study demonstrates that an integrated approach using a range of methods at landscape, site and microscopic scales of analysis can elucidate such questions. In addition, it demonstrates that in future studies, even in cases where physical remains are lacking, forensic techniques hold significant potential

Carbon exchange between a shelf sea and the ocean: The Hebrides Shelf, west of Scotland

Global mass balance calculations indicate the majority of particulate organic carbon (POC) exported from shelf seas is transferred via downslope exchange processes. Here we demonstrate the downslope flux of POC from the Hebrides Shelf is approximately 3-to-5-fold larger per unit length/area than the global mean. To reach this conclusion we quantified the offshore transport of particulate and dissolved carbon fractions via the “Ekman Drain”, a strong downwelling feature of the NW European Shelf circulation, and subsequently compared these fluxes to simultaneous regional air-sea CO2 fluxes and on-shore wind-driven Ekman fluxes to constrain the carbon dynamics of this shelf. Along the shelf break we estimate a mean offshelf total carbon (dissolved + particulate) flux of 4.2 tonnes C m−1 d−1 compared to an onshelf flux of 4.5 tonnes C m−1 d−1. Organic carbon represented 3.3% of the onshelf carbon flux but 6.4% of the offshelf flux indicating net organic carbon export. Dissolved organic carbon represented 95% and POC 5% of the exported organic carbon pool. When scaled along the shelf break the total offshelf POC flux (0.007 Tg C d−1) was found to be three times larger than the regional air-sea CO2 ingassing flux (0.0021 Tg C d−1), an order of magnitude larger than the particulate inorganic carbon flux (0.0003 Tg C d−1) but far smaller than the DIC (2.03 Tg C d−1) or DOC (0.13 Tg C d−1) fluxes. Significant spatial heterogeneity in the Ekman drain transport confirms that offshelf carbon fluxes via this mechanism are also spatially heterogeneous. This article is protected by copyright. All rights reserved

A new integrated and homogenized global monthly land surface air temperature dataset for the period since 1900

A new dataset of integrated and homogenized monthly surface air temperature over global land for the period since 1900 [China Meteorological Administration global Land Surface Air Temperature (CMA-LSAT)] is developed. In total, 14 sources have been collected and integrated into the newly developed dataset, including three global (CRUTEM4, GHCN, and BEST), three regional and eight national sources. Duplicate stations are identified, and those with the higher priority are chosen or spliced. Then, a consistency test and a climate outlier test are conducted to ensure that each station series is quality controlled. Next, two steps are adopted to assure the homogeneity of the station series: (1) homogenized station series in existing national datasets (by National Meteorological Services) are directly integrated into the dataset without any changes (50% of all stations), and (2) the inhomogeneities are detected and adjusted for in the remaining data series using a penalized maximal t test (50% of all stations). Based on the dataset, we re-assess the temperature changes in global and regional areas compared with GHCN-V3 and CRUTEM4, as well as the temperature changes during the three periods of 1900–2014, 1979–2014 and 1998–2014. The best estimates of warming trends and there 95% confidence ranges for 1900–2014 are approximately 0.102 ± 0.006 °C/decade for the whole year, and 0.104 ± 0.009, 0.112 ± 0.007, 0.090 ± 0.006, and 0.092 ± 0.007 °C/decade for the DJF (December, January, February), MAM, JJA, and SON seasons, respectively. MAM saw the most significant warming trend in both 1900–2014 and 1979–2014. For an even shorter and more recent period (1998–2014), MAM, JJA and SON show similar warming trends, while DJF shows opposite trends. The results show that the ability of CMA-LAST for describing the global temperature changes is similar with other existing products, while there are some differences when describing regional temperature changes

Effects of interspecific gene flow on the phenotypic variance–covariance matrix in Lake Victoria Cichlids

Quantitative genetics theory predicts adaptive evolution to be constrained along evolutionary lines of least resistance. In theory, hybridization and subsequent interspecific gene flow may, however, rapidly change the evolutionary constraints of a population and eventually change its evolutionary potential, but empirical evidence is still scarce. Using closely related species pairs of Lake Victoria cichlids sampled from four different islands with different levels of interspecific gene flow, we tested for potential effects of introgressive hybridization on phenotypic evolution in wild populations. We found that these effects differed among our study species. Constraints measured as the eccentricity of phenotypic variance–covariance matrices declined significantly with increasing gene flow in the less abundant species for matrices that have a diverged line of least resistance. In contrast, we find no such decline for the more abundant species. Overall our results suggest that hybridization can change the underlying phenotypic variance–covariance matrix, potentially increasing the adaptive potential of such populations

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes