The effect of prior healthcare employment on the wages of registered nurses

© 2016 The Author(s).Background: The proportion of registered nurses (RNs) with employment in health-related positions before their initial RN education has increased in the past two decades. Previous research found that prior health-related employment i

Spatiotemporal evaluation of EMEP4UK-WRF v4.3 atmospheric chemistry transport simulations of health-related metrics for NO2, O3, PM10 and PM2.5 for 2001-2010

This study was motivated by the use in air pollution epidemiology and health burden assessment of data simulated at 5 km  ×  5 km horizontal resolution by the EMEP4UK-WRF v4.3 atmospheric chemistry transport model. Thus the focus of the model–measurement comparison statistics presented here was on the health-relevant metrics of annual and daily means of NO2, O3, PM2. 5, and PM10 (daily maximum 8 h running mean for O3). The comparison was temporally and spatially comprehensive, covering a 10-year period (2 years for PM2. 5) and all non-roadside measurement data from the UK national reference monitor network, which applies consistent operational and QA/QC procedures for each pollutant (44, 47, 24, and 30 sites for NO2, O3, PM2. 5, and PM10, respectively). Two important statistics highlighted in the literature for evaluation of air quality model output against policy (and hence health)-relevant standards – correlation and bias – together with root mean square error, were evaluated by site type, year, month, and day-of-week. Model–measurement statistics were generally better than, or comparable to, values that allow for realistic magnitudes of measurement uncertainties. Temporal correlations of daily concentrations were good for O3, NO2, and PM2. 5 at both rural and urban background sites (median values of r across sites in the range 0.70–0.76 for O3 and NO2, and 0.65–0.69 for PM2. 5), but poorer for PM10 (0.47–0.50). Bias differed between environments, with generally less bias at rural background sites (median normalized mean bias (NMB) values for daily O3 and NO2 of 8 and 11 %, respectively). At urban background sites there was a negative model bias for NO2 (median NMB  =  −29 %) and PM2. 5 (−26 %) and a positive model bias for O3 (26 %). The directions of these biases are consistent with expectations of the effects of averaging primary emissions across the 5 km  ×  5 km model grid in urban areas, compared with monitor locations that are more influenced by these emissions (e.g. closer to traffic sources) than the grid average. The biases are also indicative of potential underestimations of primary NOx and PM emissions in the model, and, for PM, with known omissions in the model of some PM components, e.g. some components of wind-blown dust. There were instances of monthly and weekday/weekend variations in the extent of model–measurement bias. Overall, the greater uniformity in temporal correlation than in bias is strongly indicative that the main driver of model–measurement differences (aside from grid versus monitor spatial representivity) was inaccuracy of model emissions – both in annual totals and in the monthly and day-of-week temporal factors applied in the model to the totals – rather than simulation of atmospheric chemistry and transport processes. Since, in general for epidemiology, capturing correlation is more important than bias, the detailed analyses presented here support the use of data from this model framework in air pollution epidemiology

The Nrf2 inhibitor brusatol is a potent antitumour agent in an orthotopic mouse model of colorectal cancer

© Evans et al. Nrf2 is a transcription factor that regulates cellular stress response and irinotecan-metabolising pathways. Its aberrant activity has been reported in a number of cancers, although relatively few studies have explored a role for Nrf2 in colorectal cancer (CRC). This study assessed the expression of Nrf2 in patient CRC tissues and explored the effect of Nrf2 modulation alone, or in combination with irinotecan, in human (HCT116) and murine (CT26) cell lines in vitro and in an orthotopic syngeneic mouse model utilising bioluminescent imaging. Using a tissue microarray, Nrf2 was found to be overexpressed (p < 0.01) in primary CRC and metastatic tissue relative to normal colon, with a positive correlation between Nrf2 expression in matched primary and metastatic samples. In vitro experiments in CRC cell lines revealed that Nrf2 siRNA and brusatol, which is known to inhibit Nrf2, decreased viability and sensitised cells to irinotecan toxicity. Furthermore, brusatol effectively abrogated CRC tumour growth in subcutaneously and orthotopicallyallografted mice, resulting in an average 8-fold reduction in luminescence at the study end-point (p=0.02). Our results highlight Nrf2 as a promising drug target in the treatment of CRC

Primary cilia elongation in response to interleukin-1 mediates the inflammatory response

Primary cilia are singular, cytoskeletal organelles present in the majority of mammalian cell types where they function as coordinating centres for mechanotransduction, Wnt and hedgehog signalling. The length of the primary cilium is proposed to modulate cilia function, governed in part by the activity of intraflagellar transport (IFT). In articular cartilage, primary cilia length is increased and hedgehog signaling activated in osteoarthritis (OA). Here, we examine primary cilia length with exposure to the quintessential inflammatory cytokine interleukin-1 (IL-1), which is up-regulated in OA. We then test the hypothesis that the cilium is involved in mediating the downstream inflammatory response. Primary chondrocytes treated with IL-1 exhibited a 50 % increase in cilia length after 3 h exposure. IL-1-induced cilia elongation was also observed in human fibroblasts. In chondrocytes, this elongation occurred via a protein kinase A (PKA)-dependent mechanism. G-protein coupled adenylate cyclase also regulated the length of chondrocyte primary cilia but not downstream of IL-1. Chondrocytes treated with IL-1 exhibit a characteristic increase in the release of the inflammatory chemokines, nitric oxide and prostaglandin E2. However, in cells with a mutation in IFT88 whereby the cilia structure is lost, this response to IL-1 was significantly attenuated and, in the case of nitric oxide, completely abolished. Inhibition of IL-1-induced cilia elongation by PKA inhibition also attenuated the chemokine response. These results suggest that cilia assembly regulates the response to inflammatory cytokines. Therefore, the cilia proteome may provide a novel therapeutic target for the treatment of inflammatory pathologies, including OA

Lower cerebrospinal fluid/plasma fibroblast growth factor 21 (FGF21) ratios and placental FGF21 production in gestational diabetes

Objectives: Circulating Fibroblast Growth Factor 21 (FGF21) levels are increased in insulin resistant states such as obesity, type 2 diabetes mellitus and gestational diabetes mellitus (GDM). In addition, GDM is associated with serious maternal and fetal complications. We sought to study human cerebrospinal fluid (CSF) and corresponding circulating FGF21 levels in women with gestational diabetes mellitus (GDM) and in age and BMI matched control subjects. We also assessed FGF21 secretion from GDM and control human placental explants. Design: CSF and corresponding plasma FGF21 levels of 24 women were measured by ELISA [12 GDM (age: 26–47 years, BMI: 24.3–36.3 kg/m2) and 12 controls (age: 22–40 years, BMI: 30.1–37.0 kg/m2)]. FGF21 levels in conditioned media were secretion from GDM and control human placental explants were also measured by ELISA. Results: Glucose, HOMA-IR and circulating NEFA levels were significantly higher in women with GDM compared to control subjects. Plasma FGF21 levels were significantly higher in women with GDM compared to control subjects [234.3 (150.2–352.7) vs. 115.5 (60.5–188.7) pg/ml; P<0.05]. However, there was no significant difference in CSF FGF21 levels in women with GDM compared to control subjects. Interestingly, CSF/Plasma FGF21 ratio was significantly lower in women with GDM compared to control subjects [0.4 (0.3–0.6) vs. 0.8 (0.5–1.6); P<0.05]. FGF21 secretion into conditioned media was significantly lower in human placental explants from women with GDM compared to control subjects (P<0.05). Conclusions: The central actions of FGF21 in GDM subjects maybe pivotal in the pathogenesis of insulin resistance in GDM subjects. The significance of FGF21 produced by the placenta remains uncharted and maybe crucial in our understanding of the patho-physiology of GDM and its associated maternal and fetal complications. Future research should seek to elucidate these points

Service Oriented Big Data Management for Transport

International audienceThe increasing power of computer hardware and the sophistication of computer software have brought many new possibilities to information world. On one side the possibility to analyse massive data sets has brought new insight, knowledge and information. On the other, it has enabled to massively distribute computing and has opened to a new programming paradigm called Service Oriented Computing particularly well adapted to cloud computing. Applying these new technologies to the transport industry can bring new understanding to town transport infrastructures. The objective of our work is to manage and aggregate cloud services for managing big data and assist decision making for transport systems. Thus this paper presents our approach to propose a service oriented architecture for big data analytics for transport systems based on the cloud. Proposing big data management strategies for data produced by transport infra‐ structures, whilst maintaining cost effective systems deployed on the cloud, is a promising approach. We present the advancement for developing the Data acquisition service and Information extraction and cleaning service as well as the analysis for choosing a sharding strategy

Generalized nonreciprocity in an optomechanical circuit via synthetic magnetism and reservoir engineering

Synthetic magnetism has been used to control charge neutral excitations for applications ranging from classical beam steering to quantum simulation. In optomechanics, radiation-pressure-induced parametric coupling between optical (photon) and mechanical (phonon) excitations may be used to break time-reversal symmetry, providing the prerequisite for synthetic magnetism. Here we design and fabricate a silicon optomechanical circuit with both optical and mechanical connectivity between two optomechanical cavities. Driving the two cavities with phase-correlated laser light results in a synthetic magnetic flux, which in combination with dissipative coupling to the mechanical bath, leads to nonreciprocal transport of photons with 35dB of isolation. Additionally, optical pumping with blue-detuned light manifests as a particle non-conserving interaction between photons and phonons, resulting in directional optical amplification of 12dB in the isolator through direction. These results indicate the feasibility of utilizing optomechanical circuits to create a more general class of nonreciprocal optical devices, and further, to enable novel topological phases for both light and sound on a microchip.Comment: 18 pages, 8 figures, 4 appendice

Transactivation of EGFR by LPS induces COX-2 expression in enterocytes

Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity and mortality in preterm infants. NEC is characterized by an exaggerated inflammatory response to bacterial flora leading to bowel necrosis. Bacterial lipopolysaccharide (LPS) mediates inflammation through TLR4 activation and is a key molecule in the pathogenesis of NEC. However, LPS also induces cyclooxygenase-2 (COX-2), which promotes intestinal barrier restitution through stimulation of intestinal cell survival, proliferation, and migration. Epidermal growth factor receptor (EGFR) activation prevents experimental NEC and may play a critical role in LPS-stimulated COX-2 production. We hypothesized that EGFR is required for LPS induction of COX-2 expression. Our data show that inhibiting EGFR kinase activity blocks LPS-induced COX-2 expression in small intestinal epithelial cells. LPS induction of COX-2 requires Src-family kinase signaling while LPS transactivation of EGFR requires matrix metalloprotease (MMP) activity. EGFR tyrosine kinase inhibitors block LPS stimulation of mitogen-activated protein kinase ERK, suggesting an important role of the MAPK/ERK pathway in EGFR-mediated COX-2 expression. LPS stimulates proliferation of IEC-6 cells, but this stimulation is inhibited with either the EGFR kinase inhibitor AG1478, or the selective COX-2 inhibitor Celecoxib. Taken together, these data show that EGFR plays an important role in LPS-induction of COX-2 expression in enterocytes, which may be one mechanism for EGF in inhibition of NEC

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal