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

Flux Expulsion - Field Evolution in Neutron Stars

Models for the evolution of magnetic fields of neutron stars are constructed, assuming the field is embedded in the proton superconducting core of the star. The rate of expulsion of the magnetic flux out of the core, or equivalently the velocity of outward motion of flux-carrying proton-vortices is determined from a solution of the Magnus equation of motion for these vortices. A force due to the pinning interaction between the proton-vortices and the neutron-superfluid vortices is also taken into account in addition to the other more conventional forces acting on the proton-vortices. Alternative models for the field evolution are considered based on the different possibilities discussed for the effective values of the various forces. The coupled spin and magnetic evolution of single pulsars as well as those processed in low-mass binary systems are computed, for each of the models. The predicted lifetimes of active pulsars, field strengths of the very old neutron stars, and distribution of the magnetic fields versus orbital periods in low-mass binary pulsars are used to test the adopted field decay models. Contrary to the earlier claims, the buoyancy is argued to be the dominant driving cause of the flux expulsion, for the single as well as the binary neutron stars. However, the pinning is also found to play a crucial role which is necessary to account for the observed low field binary and millisecond pulsars.Comment: 23 pages, + 7 figures, accepted for publication in Ap

Late Holocene climate reorganisation and the North American Monsoon

The North America Monsoon (NAM) provides the majority of rainfall for central and northern Mexico as well as parts of the south west USA. The controls over the strength of the NAM in a given year are complex, and include both Pacific and Atlantic systems. We present here an annually resolved proxy reconstruction of NAM rainfall variability over the last ~6ka, from an inwash record from the Laguna de Juanacatlán, Mexico. This high resolution, exceptionally well dated record allows changes in the NAM through the latter half of the Holocene to be investigated in both time and space domains, improving our understanding of the controls on the system. Our analysis shows a shift in conditions between c. 4 and 3 ka BP, after which clear ENSO/PDO type forcing patterns are evident

Long term cost effectiveness of interventions for obesity:A Mendelian randomisation study

Background The prevalence of obesity has increased in the United Kingdom, and reliably measuring the impact on quality of life and the total healthcare cost from obesity is key to informing the cost-effectiveness of interventions that target obesity, and determining healthcare funding. Current methods for estimating cost-effectiveness of interventions for obesity may be subject to confounding and reverse causation. The aim of this study is to apply a new approach using mendelian randomisation for estimating the cost-effectiveness of interventions that target body mass index (BMI), which may be less affected by confounding and reverse causation than previous approaches. Methods and findings We estimated health-related quality-adjusted life years (QALYs) and both primary and secondary healthcare costs for 310,913 men and women of white British ancestry aged between 39 and 72 years in UK Biobank between recruitment (2006 to 2010) and 31 March 2017. We then estimated the causal effect of differences in BMI on QALYs and total healthcare costs using mendelian randomisation. For this, we used instrumental variable regression with a polygenic risk score (PRS) for BMI, derived using a genome-wide association study (GWAS) of BMI, with age, sex, recruitment centre, and 40 genetic principal components as covariables to estimate the effect of a unit increase in BMI on QALYs and total healthcare costs. Finally, we used simulations to estimate the likely effect on BMI of policy relevant interventions for BMI, then used the mendelian randomisation estimates to estimate the cost-effectiveness of these interventions. A unit increase in BMI decreased QALYs by 0.65% of a QALY (95% confidence interval [CI]: 0.49% to 0.81%) per year and increased annual total healthcare costs by £42.23 (95% CI: £32.95 to £51.51) per person. When considering only health conditions usually considered in previous cost-effectiveness modelling studies (cancer, cardiovascular disease, cerebrovascular disease, and type 2 diabetes), we estimated that a unit increase in BMI decreased QALYs by only 0.16% of a QALY (95% CI: 0.10% to 0.22%) per year. We estimated that both laparoscopic bariatric surgery among individuals with BMI greater than 35 kg/m2, and restricting volume promotions for high fat, salt, and sugar products, would increase QALYs and decrease total healthcare costs, with net monetary benefits (at £20,000 per QALY) of £13,936 (95% CI: £8,112 to £20,658) per person over 20 years, and £546 million (95% CI: £435 million to £671 million) in total per year, respectively. The main limitations of this approach are that mendelian randomisation relies on assumptions that cannot be proven, including the absence of directional pleiotropy, and that genotypes are independent of confounders. Conclusions Mendelian randomisation can be used to estimate the impact of interventions on quality of life and healthcare costs. We observed that the effect of increasing BMI on health-related quality of life is much larger when accounting for 240 chronic health conditions, compared with only a limited selection. This means that previous cost-effectiveness studies have likely underestimated the effect of BMI on quality of life and, therefore, the potential cost-effectiveness of interventions to reduce BMI

Sleep disturbances and patterns in children with neurodevelopmental conditions

Background: Children with neurodevelopmental conditions (NDC) often experience sleep problems which are long-lasting and more complex than typically developing children. These sleep problems impact their families and there is little guidance for management specifically for sleep for families of children with neurodevelopmental conditions. The present study aims to use parental report to evaluate sleep disturbances and sleep patterns in a large sample of children with NDC. We aim to identify associations with age, diagnosis, and medication groups. Methods: Data on 601 children aged between 2 and 17 years was analyzed from a UK non-profit service for sleep for families of children with NDC. Parents/carers completed the children's sleep habit questionnaire, a 7 day sleep diary, and information on child age, diagnosis, and medication. Parents also reported previous sleep management techniques they had tried. Results: Overall, we found differences between age, diagnosis, and medication use groups for sleep disturbances and sleep diary parameters in these populations. Sensory conditions were associated with high night time waking duration. Parents reported their child's short sleep duration was the most common problem for them. Conclusions: Key areas for further research are outlined including the long term considerations for parental presence at bedtime for sleep anxiety, melatonin use and efficacy, and consideration for interventions to reduce daytime fatigue in children aged 7–11 years old

The Fornax Spectroscopic Survey I. Survey Strategy and Preliminary Results on the Redshift Distribution of a Complete Sample of Stars and Galaxies

The Fornax Spectroscopic Survey will use the Two degree Field spectrograph (2dF) of the Anglo-Australian Telescope to obtain spectra for a complete sample of all 14000 objects with 16.5<=Bj<=19.7 in a 12 square degree area centred on the Fornax Cluster. By selecting all objects---both stars and galaxies---independent of morphology, we cover a much larger range of surface brightness and scale size than previous surveys. In this paper we present results from the first 2dF field. Redshift distributions and velocity structures are shown for all observed objects in the direction of Fornax, including Galactic stars, galaxies in and around the Fornax Cluster, and for the background galaxy population. The velocity data for the stars show the contributions from the different Galactic components, plus a small tail to high velocities. We find no galaxies in the foreground to the cluster in our 2dF field. The Fornax Cluster is clearly defined kinematically. The mean velocity from the 26 cluster members having reliable redshifts is 1560+/-80 km/s. They show a velocity dispersion of 380+/-50 km/s. Large-scale structure can be traced behind the cluster to a redshift beyond z=0.3. Background compact galaxies and low surface brightness galaxies are found to follow the general galaxy distribution.Comment: LaTeX format; uses aa.cls (included). Accepted for publication in Astronomy and Astrophysic

Mesonic decay constants in lattice NRQCD

Lattice NRQCD with leading finite lattice spacing errors removed is used to calculate decay constants of mesons made up of heavy quarks. Quenched simulations are done with a tadpole improved gauge action containing plaquette and six-link rectangular terms. The tadpole factor is estimated using the Landau link. For each of the three values of the coupling constant considered, quarkonia are calculated for five masses spanning the range from charmonium through bottomonium, and one set of quark masses is tuned to the B(c). "Perturbative" and nonperturbative meson masses are compared. One-loop perturbative matching of lattice NRQCD with continuum QCD for the heavy-heavy vector and axial vector currents is performed. The data are consistent with the vector meson decay constants of quarkonia being proportional to the square root of their mass and the B(c) decay constant being equal to 420(13) MeV.Comment: 25 pages in REVTe