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

Histiocytoid cardiomyopathy and microphthalmia with linear skin defects syndrome: phenotypes linked by truncating variants in NDUFB11

Variants in NDUFB11, which encodes a structural component of complex I of the mitochondrial respiratory chain (MRC), were recently independently reported to cause histiocytoid cardiomyopathy (histiocytoid CM) and microphthalmia with linear skin defects syndrome (MLS syndrome). Here we report an additional case of histiocytoid CM, which carries a de novo nonsense variant in NDUFB11 (ENST00000276062.8: c.262C > T; p.[Arg88*]) identified using whole-exome sequencing (WES) of a family trio. An identical variant has been previously reported in association with MLS syndrome. The case we describe here lacked the diagnostic features of MLS syndrome, but a detailed clinical comparison of the two cases revealed significant phenotypic overlap. Heterozygous variants in HCCS (which encodes an important mitochondrially targeted protein) and COX7B, which, like NDUFB11, encodes a protein of the MRC, have also previously been identified in MLS syndrome including a case with features of both MLS syndrome and histiocytoid CM. However, a systematic review of WES data from previously published histiocytoid CM cases, alongside four additional cases presented here for the first time, did not identify any variants in these genes. We conclude that NDUFB11 variants play a role in the pathogenesis of both histiocytoid CM and MLS and that these disorders are allelic (genetically related)

The promotion of local wellbeing: A primer for policymakers

There is growing interest among policymakers in the promotion of wellbeing as an objective of public policy. In particular, local authorities have been given powers to undertake action to promote wellbeing in their area. Recent advances in the academic literature on wellbeing are giving rise to an increasingly detailed picture of the factors that determine people’s subjective wellbeing (how they think and feel about their lives). However, the concept of subjective wellbeing is poorly understood within local government and much of the evidence base is extremely recent. I therefore review the literature on the definition, measurement, and determinants of wellbeing, and discuss some of its implications for local public policy

Electrohydrodynamic and Aerosol Jet Printing for the Copatterning of Polydimethylsiloxane and Graphene Platelet Inks

The performance of soft sensing and actuation devices is dependent on their design, the electro‐mechanical response of materials, and the ability to copattern structural and functional features. For film based soft structures, such as wearable sensors and artificial muscles, manufacturing challenges exist that prevent the translation of technology from laboratory to practical application. In this work, a hybrid manufacturing technique is presented that integrates electro‐hydrodynamic and aerosol jet deposition to print multilayer, multimaterial structures. The combined approach overcomes the respective rheological constraints of the individual processes, while presenting a pathway to higher resolution computer‐controlled patterning. Electro‐hydrodynamic deposition of a polydimethylsiloxane elastomer is demonstrated and characterized, before being combined with aerosol jet deposition of a graphene platelet ink to produce functional devices. A proof‐of‐concept, multilayer capacitive sensor is presented as a first demonstration of the manufacturing technology

The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer

The contractile actin-myosin cytoskeleton provides much of the force required for numerous cellular activities such as motility, adhesion, cytokinesis and changes in morphology. Key elements that respond to various signal pathways are the myosin II regulatory light chains (MLC), which participate in actin-myosin contraction by modulating the ATPase activity and consequent contractile force generation mediated by myosin heavy chain heads. Considerable effort has focussed on the role of MLC kinases, and yet the contributions of the myotonic dystrophy-related Cdc42-binding kinases (MRCK) proteins in MLC phosphorylation and cytoskeleton regulation have not been well characterized. In contrast to the closely related ROCK1 and ROCK2 kinases that are regulated by the RhoA and RhoC GTPases, there is relatively little information about the CDC42-regulated MRCKα, MRCKβ and MRCKγ members of the AGC (PKA, PKG and PKC) kinase family. As well as differences in upstream activation pathways, MRCK and ROCK kinases apparently differ in the way that they spatially regulate MLC phosphorylation, which ultimately affects their influence on the organization and dynamics of the actin-myosin cytoskeleton. In this review, we will summarize the MRCK protein structures, expression patterns, small molecule inhibitors, biological functions and associations with human diseases such as cancer

WHO collaborative study to assess the suitability of the 1st International Standard and the 1st International Reference Panel for antibodies to Ebola virus

A WHO international collaborative study was undertaken to evaluate preparations of Ebola virus disease (EVD) convalescent plasmas for their suitability to serve as the WHO 1st International Standard (IS) and the WHO 1st International Reference Panel (IRP) for Ebola virus antibodies for use in the standardization and control of assays. The study involved participants testing the convalescent plasma sample preparations and additional monoclonal antibody samples in a blinded manner alongside the WHO International Reference Reagent (NIBSC code 15/220) using anti-EBOV assays established in their laboratories. The candidate 1st IS for Ebola virus antibodies (study sample code 92, NIBSC 15/262) consists of ampoules containing the freeze-dried equivalent of 0.5 mL pooled convalescent plasma obtained from six Sierra Leone patients recovered from EVD. The candidate 1st IRP of anti-Ebola virus convalescent plasmas (NIBSC 16/344) consists of freeze-dried preparations of single donations of convalescent plasma obtained from four patients and one healthy blood donor. Each panel member is an ampoule containing the equivalent of 0.25mL plasma. All convalescent plasmas are confirmed PCR-negative for Ebola virus and underwent, along with the negative plasma, solvent detergent (SD) treatment prior to their development into candidate WHO biological reference materials. In this collaborative study, 17 laboratories from 4 countries used a range of live Ebola virus neutralization assays, pseudotyped virus neutralisation assays and enzyme immunoassays to test the collaborative study samples. Surface plasmon resonance and Western blot assessments were also undertaken. The study found that the candidate International Standard has the highest absolute titre among the convalescent plasma samples, although the geometric mean titres of all the convalescent plasmas fall within ~5-fold of each other. The potencies of three of the convalescent samples fall near the detection limit of some assays. This study also demonstrated that the agreement between laboratories for potencies relative to the candidate International Standard represents an improvement compared to the agreement in absolute titres; however, there is poor agreement between relative potencies for some assays. The results obtained from accelerated thermal degradation studies at 1year indicate that the candidate IS is stable and suitable for long-term use. The results of the collaborative study indicate the suitability of the candidates to serve as WHO reference materials and it is proposed that 15/262 is established as the WHO 1st IS for EBOV antibodies with an assigned potency of 1.5 IU/mL when reconstituted as directed in the instructions for use. It is also proposed that 16/344 is established as the WHO 1st IRP of anti-EBOV convalescent plasmas with panel member code 95 (NIBSC 15/280) assigned a unitage of 1.1 IU/mL when reconstituted as directed in the instructions for use. The other panel members have not been assigned a unitage. The implementation and use by laboratories of the proposed WHO reference materials for EBOV antibodies will facilitate the characterization of the factors that contribute to assay variability and standardization of results across assays and laboratorie

CMB Telescopes and Optical Systems

The cosmic microwave background radiation (CMB) is now firmly established as a fundamental and essential probe of the geometry, constituents, and birth of the Universe. The CMB is a potent observable because it can be measured with precision and accuracy. Just as importantly, theoretical models of the Universe can predict the characteristics of the CMB to high accuracy, and those predictions can be directly compared to observations. There are multiple aspects associated with making a precise measurement. In this review, we focus on optical components for the instrumentation used to measure the CMB polarization and temperature anisotropy. We begin with an overview of general considerations for CMB observations and discuss common concepts used in the community. We next consider a variety of alternatives available for a designer of a CMB telescope. Our discussion is guided by the ground and balloon-based instruments that have been implemented over the years. In the same vein, we compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the South Pole Telescope (SPT). CMB interferometers are presented briefly. We conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and Planck, to demonstrate a remarkable evolution in design, sensitivity, resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1: Telescopes and Instrumentatio

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Application of silver in microtubular solid oxide fuel cells

In this paper, the behaviour of silver as cathode conductive material, interconnect wire, and sealing for anode lead connection for microtubular solid oxide fuel cells (µSOFC) is reported. The changes in silver morphology are examined by scanning electron microscopy on cells that had been operated under reformed methane. It is found that using silver in an solid oxide fuel cell (SOFC) stack can improve the cell performance. However, it is also concluded that silver may be responsible for cell degradation. This report brings together and explains all the known problems with application of silver for SOFCs. The results show that silver is unstable in interconnect and in cathode environments. It is found that the process of cell passivation/activation promotes silver migration. The difference in thermal expansion of silver and sealant results in damage to the glass. It is concluded that when silver is exposed to a dual atmosphere condition, high levels of porosity formation is seen in the dense silver interconnect. The relevance of application of silver in SOFC stacks is discussed