Step Change in Improving the Accuracy of Nitrous Oxide Reference Materials for Underpinning Atmospheric Composition Measurements.

We have employed a new approach to quantify the amount fraction of nitrous oxide in a synthetic air matrix gas used to prepare high-accuracy reference materials of the same component. Until now, this was the largest contributor to the measurement uncertainty of nitrous oxide in air reference materials at atmospheric amount fractions (∼330 nmol mol-1), as identified in a recent international comparison. A novel preconcentration method has resulted in a measurement of 363 pmol mol-1 of nitrous oxide in a synthetic air matrix gas with an expanded uncertainty of 27 pmol mol-1. This represents a significant breakthrough as using these developments with an optimized dilution hierarchy (to minimize the gravimetric uncertainty) promises to result in SI traceable reference materials with expanded uncertainties as low as 0.032% relative (k = 2). This supports the World Meteorological Organization-Global Atmosphere Watch network compatibility goal for underpinning atmospheric observations.

Can educational video resources improve learning when used to augment traditional teaching of clinical examination? A randomized control trial of novice medical students.

BACKGROUND: Good clinical examination skills can both increase the quality of patient care and reduce its cost. A previous study by our group demonstrated that face-to-face training is the gold standard for teaching these skills. It is unclear if high quality educational videos can augment this teaching. METHODS: Forty-two Medical Students naïve to large joint examination were recruited and block randomised to two groups. The control group had face-to-face teaching alone. The intervention group had their teaching augmented with a custom educational video accessed via a web portal. Participants were assessed on their examination of a large joint using a previously standardised assessment tool at baseline and 7 days post intervention. Assessors were blinded to intervention type. RESULTS: There was no significant difference in the mean baseline scores. Mean baseline scores were 3.35 (11.2%, SD = 2.2, SE = 0.49) for the face-to-face only group and 2.65 (8.8%, SD = 1.39, SE = 0.31) for the video adjunct group [p = 0.137]. There was a significant difference in the improvement in score after intervention between each group [p = 0.005]. The mean improvement in score was 15.42 (SD = 5.64, SE = 1.29) for the face-to-face only group and 20.68 (SD = 4.33,SE = 0.99) for the video adjunct group. CONCLUSION: When used as an adjunct to more traditional face-to-face teaching methods, a custom-made educational video significantly improves the teaching of clinical examination skills and there is a role for these resources in augmenting traditional teaching methods.

Characterization of Fourier Transform Infrared, Cavity Ring-Down Spectroscopy, and Optical Feedback Cavity-Enhanced Absorption Spectroscopy Instruments for the Analysis of Ammonia in Biogas and Biomethane.

Novel traceable analytical methods and reference gas standards were developed for the detection of trace-level ammonia in biogas and biomethane. This work focused on an ammonia amount fraction at an upper limit level of 10 mg m-3 (corresponding to approximately 14 µmol mol-1) specified in EN 16723-1:2016. The application of spectroscopic analytical methods, such as Fourier transform infrared spectroscopy, cavity ring-down spectroscopy, and optical feedback cavity-enhanced absorption spectroscopy, was investigated. These techniques all exhibited the necessary ammonia sensitivity at the required 14 µmol mol-1 amount fraction. A 29-month stability study of reference gas mixtures of 10 µmol mol-1 ammonia in methane and synthetic biogas is also reported.

Isotopically characterised N2 O reference materials for use as community standards.

RATIONALE: Information on the isotopic composition of nitrous oxide (N2 O) at natural abundance supports the identification of its source and sink processes. In recent years, a number of mass spectrometric and laser spectroscopic techniques have been developed and are increasingly used by the research community. Advances in this active research area, however, critically depend on the availability of suitable N2 O isotope Reference Materials (RMs). METHODS: Within the project Metrology for Stable Isotope Reference Standards (SIRS), seven pure N2 O isotope RMs have been developed and their 15 N/14 N, 18 O/16 O, 17 O/16 O ratios and 15 N site preference (SP) have been analysed by specialised laboratories against isotope reference materials. A particular focus was on the 15 N site-specific isotopic composition, as this measurand is both highly diagnostic for source appointment and challenging to analyse and link to existing scales. RESULTS: The established N2 O isotope RMs offer a wide spread in delta (δ) values: δ15 N: 0 to +104‰, δ18 O: +39 to +155‰, and δ15 NSP : -4 to +20‰. Conversion and uncertainty propagation of δ15 N and δ18 O to the Air-N2 and VSMOW scales, respectively, provides robust estimates for δ15 N(N2 O) and δ18 O(N2 O), with overall uncertainties of about 0.05‰ and 0.15‰, respectively. For δ15 NSP , an offset of >1.5‰ compared with earlier calibration approaches was detected, which should be revisited in the future. CONCLUSIONS: A set of seven N2 O isotope RMs anchored to the international isotope-ratio scales was developed that will promote the implementation of the recommended two-point calibration approach. Particularly, the availability of δ17 O data for N2 O RMs is expected to improve data quality/correction algorithms with respect to δ15 NSP and δ15 N analysis by mass spectrometry. We anticipate that the N2 O isotope RMs will enhance compatibility between laboratories and accelerate research progress in this emerging field.

Fibula nail fixation in ankle fractures with significant soft tissue compromise: a retrospective cohort study.

PURPOSE: Intramedullary fixation of lateral malleolar fractures has increased in popularity recently with the introduction of the fibula nail. It has been proposed as an alternative fixation method in fractures to minimise soft tissue injury. The aim of this study was to evaluate the clinical and patient-reported outcomes of those who had an ankle fracture with concurrent significant soft tissue damage, treated with a fibula nail. METHODS: Details of patients who were managed at our institution using a fibula nail were obtained from the trauma database. The Acumed Fibula Rod System (FRS) was used in all cases. Those who were less than 12 months following injury were excluded. Patients attended a follow-up clinic for measurement of range of movement, radiographs, and to complete MOX-FQ and EQ-5D questionnaires. RESULTS: Twenty patients were identified. Eleven attended for review in person, and a further eight completed questionnaires (questionnaire response rate 95%). The mean age was 59 years (range 19-91). Twelve fractures were open, all of which were initially managed using an external fixator. One patient developed deep infection necessitating fusion. The mean MOX-FQ and EQ-5D scores were 53.6 and 0.649, respectively, at a median of 40 months post-injury. The mean EQ-VAS was 70. The range of movement of the affected side was significantly less than the unaffected side (p < 0.001 on paired t-test). CONCLUSION: This study suggests that the FRS offers a reliable and acceptable alternative fixation technique for patients who have significant soft tissue injuries.

Redefinition of the Mole in the Revised International System of Units and the Ongoing Importance of Metrology for Accurate Chemical Measurements.

This Feature highlights the role of metrology, the science of measurement, in maintaining the infrastructure we all rely on for accurate chemical measurements. In particular, the recent change to the definition of the mole, the unit of chemistry, is explained.

A high-throughput chemical-genetics screen in murine adipocytes identifies insulin-regulatory pathways.

Pathways linking activation of the insulin receptor to downstream targets of insulin have traditionally been studied using a candidate gene approach. To elucidate additional pathways regulating insulin activity, we performed a forward chemical-genetics screen based on translocation of a glucose transporter 4 (Glut4) reporter expressed in murine 3T3-L1 adipocytes. To identify compounds with known targets, we screened drug-repurposing and natural product libraries. We identified, confirmed, and validated 64 activators and 65 inhibitors that acutely increase or rapidly decrease cell-surface Glut4 in adipocytes stimulated with submaximal insulin concentrations. These agents were grouped by target, chemical class, and mechanism of action. All groups contained multiple hits from a single drug class, and several comprised multiple structurally unrelated hits for a single target. Targets include the ß-adrenergic and adenosine receptors. Agonists of these receptors increased and inverse agonists/antagonists decreased cell-surface Glut4 independently of insulin. Additional activators include insulin sensitizers (thiazolidinediones), insulin mimetics, dis-inhibitors (the mTORC1 inhibitor rapamycin), cardiotonic steroids (the Na+/K+-ATPase inhibitor ouabain), and corticosteroids (dexamethasone). Inhibitors include heterocyclic amines (tricyclic antidepressants) and 21 natural product supplements and herbal extracts. Mechanisms of action include effects on Glut4 trafficking, signal transduction, inhibition of protein synthesis, and dissipation of proton gradients. Two pathways that acutely regulate Glut4 translocation were discovered: de novo protein synthesis and endocytic acidification. The mechanism of action of additional classes of activators (tanshinones, dalbergiones, and coumarins) and inhibitors (flavonoids and resveratrol) remains to be determined. These tools are among the most sensitive, responsive, and reproducible insulin-activity assays described to date.

Radon as a natural tracer of gas transport through trees.

Trees are sources, sinks, and conduits for gas exchange between the atmosphere and soil, and effectively link these terrestrial realms in a soil-plant-atmosphere continuum. We demonstrated that naturally produced radon-222 (222 Rn) gas has the potential to disentangle the biotic and physical processes that regulate gas transfer between soils or plants and the atmosphere in field settings where exogenous tracer applications are challenging. Patterns in stem radon emissions across tree species, seasons, and diurnal periods suggest that plant transport of soil gases is controlled by plant hydraulics, whether by diffusion or mass flow via transpiration. We establish for the first time that trees emit soil gases during the night when transpiration rates are negligible, suggesting that axial diffusion is an important and understudied mechanism of plant and soil gas transmission.

Synthetic Zero Air Reference Material for High Accuracy Greenhouse Gas Measurements.

The purity analysis of zero air is a significant contributor to the uncertainty in preparing reference materials of high impact greenhouse gases, limiting progress toward coherent and comparable measurements required to assess climate trends. We have produced a commutable synthetic zero air reference material with an oxygen, nitrogen, and argon matrix closely matching atmospheric composition. This is the critical step in preventing systematic biases from pressure broadening effects when using these reference materials to calibrate instruments based on optical spectroscopy. The amount fractions of carbon dioxide, methane, and carbon monoxide, which are present as minor impurities in the zero air reference material, have been accurately quantified using a novel dilution device that can generate gas mixtures of these components at trace amount fractions. These developments will have a significant impact on advancing the state of the art in high accuracy reference materials and for baseline calibration of spectroscopic instrumentation.

Breakthrough in Negating the Impact of Adsorption in Gas Reference Materials.

We have shown that an exchange dilution preparation method reduces the impact of surface adsorption of the target component in high-pressure gas mixtures used for underpinning measurements of amount-of-substance fraction. Gas mixtures are diluted in the same cylinder by releasing an aliquot of the parent mixture. Additional matrix gas is then added to the cylinder. This differs from conventional methods where dilutions are achieved by transferring the parent mixture to another cylinder, which then stores the final reference material. The benefit of this revolutionary approach is that losses due to adsorption to the walls of the cylinder and the valve are reduced as the parent mixture pacifies the surface with only a negligible relative change in amount-of-substance fraction. This development allows for preparation of gas reference materials with unprecedented uncertainties beyond the existing state of the art. It has significant implications for the preparation of high accuracy gas reference materials which underpin a broad range of requirements, particularly in atmospheric monitoring of carbon dioxide, where understanding the adsorption effects is the major obstacle to advancing the measurement science. It has the potential to remove the reliance on proprietary surface pretreatments as the method provides an in situ and consistent alternative.

Methane emissions from tree stems: a new frontier in the global carbon cycle.

Tree stems from wetland, floodplain and upland forests can produce and emit methane (CH4 ). Tree CH4 stem emissions have high spatial and temporal variability, but there is no consensus on the biophysical mechanisms that drive stem CH4 production and emissions. Here, we summarize up to 30 opportunities and challenges for stem CH4 emissions research, which, when addressed, will improve estimates of the magnitudes, patterns and drivers of CH4 emissions and trace their potential origin. We identified the need: (1) for both long-term, high-frequency measurements of stem CH4 emissions to understand the fine-scale processes, alongside rapid large-scale measurements designed to understand the variability across individuals, species and ecosystems; (2) to identify microorganisms and biogeochemical pathways associated with CH4 production; and (3) to develop a mechanistic model including passive and active transport of CH4 from the soil-tree-atmosphere continuum. Addressing these challenges will help to constrain the magnitudes and patterns of CH4 emissions, and allow for the integration of pathways and mechanisms of CH4 production and emissions into process-based models. These advances will facilitate the upscaling of stem CH4 emissions to the ecosystem level and quantify the role of stem CH4 emissions for the local to global CH4 budget.

Soil aggregates as biogeochemical reactors and implications for soil-atmosphere exchange of greenhouse gases-A concept.

Soil-atmosphere exchange significantly influences the global atmospheric abundances of carbon dioxide (CO2 ), methane (CH4 ), and nitrous oxide (N2 O). These greenhouse gases (GHGs) have been extensively studied at the soil profile level and extrapolated to coarser scales (regional and global). However, finer scale studies of soil aggregation have not received much attention, even though elucidating the GHG activities at the full spectrum of scales rather than just coarse levels is essential for reducing the large uncertainties in the current atmospheric budgets of these gases. Through synthesizing relevant studies, we propose that aggregates, as relatively separate micro-environments embedded in a complex soil matrix, can be viewed as biogeochemical reactors of GHGs. Aggregate reactivity is determined by both aggregate size (which determines the reactor size) and the bulk soil environment including both biotic and abiotic factors (which further influence the reaction conditions). With a systematic, dynamic view of the soil system, implications of aggregate reactors for soil-atmosphere GHG exchange are determined by both an individual reactor's reactivity and dynamics in aggregate size distributions. Emerging evidence supports the contention that aggregate reactors significantly influence soil-atmosphere GHG exchange and may have global implications for carbon and nitrogen cycling. In the context of increasingly frequent and severe disturbances, we advocate more analyses of GHG activities at the aggregate scale. To complement data on aggregate reactors, we suggest developing bottom-up aggregate-based models (ABMs) that apply a trait-based approach and incorporate soil system heterogeneity.

Origin and Fate of Vanadium in the Hazeltine Creek Catchment following the 2014 Mount Polley Mine Tailings Spill in British Columbia, Canada.

Results from the analysis of aqueous and solid-phase V speciation within samples collected from the Hazeltine Creek catchment affected by the August 2014 Mount Polley mine tailings dam failure in British Columbia, Canada, are presented. Electron microprobe and X-ray absorption near-edge structure (XANES) analysis found that V is present as V3+ substituted into magnetite and V3+ and V4+ substituted into titanite, both of which occur in the spilled Mount Polley tailings. Secondary Fe oxyhydroxides forming in inflow waters and on creek beds have V K-edge XANES spectra exhibiting E1/2 positions and pre-edge features consistent with the presence of V5+ species, suggesting sorption of this species on these secondary phases. PHREEQC modeling suggests that the stream waters mostly contain V5+ and the inflow and pore waters contain a mixture of V3+ and V5+. These data, and stream, inflow, and pore water chemical data, suggest that dissolution of V(III)-bearing magnetite, V(III)- and V(IV)-bearing titanite, V(V)-bearing Fe(-Al-Si-Mn) oxhydroxides, and V-bearing Al(OH)3 and/or clay minerals may have occurred. In the circumneutral pH environment of Hazeltine Creek, elevated V concentrations are likely naturally attenuated by formation of V(V)-bearing secondary Fe oxyhydroxide, Al(OH)3, or clay mineral colloids, suggesting that the V is not bioavailable. A conceptual model describing the origin and fate of V in Hazeltine Creek that is applicable to other river systems is presented.

Heavy Metal Soil Contamination Detection Using Combined Geochemistry and Field Spectroradiometry in the United Kingdom.

Technological advances in hyperspectral remote sensing have been widely applied in heavy metal soil contamination studies, as they are able to provide assessments in a rapid and cost-effective way. The present work investigates the potential role of combining field and laboratory spectroradiometry with geochemical data of lead (Pb), zinc (Zn), copper (Cu) and cadmium (Cd) in quantifying and modelling heavy metal soil contamination (HMSC) for a floodplain site located in Wales, United Kingdom. The study objectives were to: (i) collect field- and lab-based spectra from contaminated soils by using ASD FieldSpec® 3, where the spectrum varies between 350 and 2500 nm; (ii) build field- and lab-based spectral libraries; (iii) conduct geochemical analyses of Pb, Zn, Cu and Cd using atomic absorption spectrometer; (iv) identify the specific spectral regions associated to the modelling of HMSC; and (v) develop and validate heavy metal prediction models (HMPM) for the aforementioned contaminants, by considering their spectral features and concentrations in the soil. Herein, the field- and lab-based spectral features derived from 85 soil samples were used successfully to develop two spectral libraries, which along with the concentrations of Pb, Zn, Cu and Cd were combined to build eight HMPMs using stepwise multiple linear regression. The results showed, for the first time, the feasibility to predict HMSC in a highly contaminated floodplain site by combining soil geochemistry analyses and field spectroradiometry. The generated models help for mapping heavy metal concentrations over a huge area by using space-borne hyperspectral sensors. The results further demonstrated the feasibility of combining geochemistry analyses with filed spectroradiometric data to generate models that can predict heavy metal concentrations.

Influence of Pressure on the Composition of Gaseous Reference Materials.

We have shown that the amount fraction of carbon dioxide in a nitrogen or synthetic air matrix stored in cylinders increases as the pressure of the gas mixture reduces, while the amount fraction of methane remains unchanged. Our measurements show the initial amount fraction of carbon dioxide to be lower than the gravimetric value after preparation, which we attribute to the adsorption of a proportion of the molecules to active sites on the internal surface of the cylinder and the valve. As the mixture is consumed, the pressure in the cylinder reduces and the amount fraction of the component is observed to increase. The effect is less pronounced in the presence of water vapor. More dramatic effects have been observed for hydrogen chloride. These findings have significant implications for the preparation of high accuracy gaseous reference materials with unprecedented uncertainties which underpin a broad range of requirements, in particular atmospheric monitoring of high impact greenhouse gases.

Vehicle-Based Methane Surveys for Finding Natural Gas Leaks and Estimating Their Size: Validation and Uncertainty.

Managing leaks in urban natural gas (NG) distribution systems is important for reducing methane emissions and costly waste. Mobile surveying technologies have emerged as a new tool for monitoring system integrity, but this new technology has not yet been widely adopted. Here, we establish the efficacy of mobile methane surveys for managing local NG distribution systems by evaluating their ability to detect and locate NG leaks and quantify their emissions. In two cities, three-quarters of leak indications from mobile surveys corresponded to NG leaks, but local distribution companies' field crews did not find most of these leaks, indicating that the national CH4 activity factor for leaks in local NG distribution pipelines is underestimated by a factor of 2.4. We found the median distance between mobile-estimated leak locations and actual leak locations was 19 m. A comparison of emission quantification methods (mobile-based, surface enclosure, and tracer ratio) found that the mobile method overestimated leak magnitude for the smallest leaks but accurately estimated size for the largest leaks that are responsible for the majority of total emissions. Across leak sizes, mobile methods adequately rank relative emission rates for repair prioritization, and they are easily deployed and offer efficient spatial coverage.

SU9516 Increases α7ß1 Integrin and Ameliorates Disease Progression in the mdx Mouse Model of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a fatal muscle disease caused by mutations in the dystrophin gene, resulting in a complete loss of the dystrophin protein. Dystrophin is a critical component of the dystrophin glycoprotein complex (DGC), which links laminin in the extracellular matrix to the actin cytoskeleton within myofibers and provides resistance to shear stresses during muscle activity. Loss of dystrophin in DMD patients results in a fragile sarcolemma prone to contraction-induced muscle damage. The α7ß1 integrin is a laminin receptor protein complex in skeletal and cardiac muscle and a major modifier of disease progression in DMD. In a muscle cell-based screen for α7 integrin transcriptional enhancers, we identified a small molecule, SU9516, that promoted increased α7ß1 integrin expression. Here we show that SU9516 leads to increased α7B integrin in murine C2C12 and human DMD patient myogenic cell lines. Oral administration of SU9516 in the mdx mouse model of DMD increased α7ß1 integrin in skeletal muscle, ameliorated pathology, and improved muscle function. We show that these improvements are mediated through SU9516 inhibitory actions on the p65-NF-κB pro-inflammatory and Ste20-related proline alanine rich kinase (SPAK)/OSR1 signaling pathways. This study identifies a first in-class α7 integrin-enhancing small-molecule compound with potential for the treatment of DMD.

Geroderma osteodysplasticum: Histological features and the role of panel-based exome sequencing in diagnosis.

Geroderma osteodysplasticum (GO) has clinical and histological features that overlap with other causes of wrinkly skin. Here we present the case of a child diagnosed with GO following exome sequencing of a panel of genes covering the wide differential diagnosis. The histological features of the overlapping conditions are presented, highlighting the utility of panel testing for conditions of this type. This is relevant to many genetic conditions and can influence ongoing management as exemplified by this case.

CCQM-K121 - Monoterpenes in Nitrogen at 2.5 nmol mol-1 Final Report.

The growing awareness of climate change, and continuing concerns regarding tropospheric and stratospheric chemistry, will require future measurements and standards for compounds linked to these issues. To globally monitor and control the emissions of these species in the atmosphere, it is necessary to demonstrate measurement equivalence at the highest levels of accuracy for assigned values of standards. This report describes the results of a key comparison for several important monoterpene species, which are relevant to atmospheric chemistry and climate. The comparison samples include α-pinene, 3-carene, R-limonene and 1,8-cineole in a nitrogen matrix gas, at a 2.5 nmol mol-1 amount-of-substance fraction. The objective of this key comparison is to evaluate the participants' capabilities to measure trace-level monoterpenes using their own calibration techniques.