Unreported VOC Emissions from Road Transport Including from Electric Vehicles.

There are widespread policy assumptions that the phase-out of gasoline and diesel internal combustion engines will over time lead to much reduced emissions of Volatile Organic Compounds (VOCs) from road transport and related fuels. However, the use of real-world emissions measurements from a new mobile air quality monitoring station demonstrated a large underestimation of alcohol-based species in road transport emissions inventories. Scaling of industry sales statistics enabled the discrepancy to be attributed to the use of ancillary solvent products such as screenwash and deicer which are not included in internationally applied vehicle emission methodologies. A fleet average nonfuel nonexhaust VOC emission factor of 58 ± 39 mg veh-1 km-1 was calculated for the missing source, which is greater than the total of all VOCs emitted from vehicle exhausts and their associated evaporative fuel losses. These emissions are independent of the vehicle energy/propulsion system and therefore applicable to all road vehicle types including those with battery-electric powertrains. In contrast to predictions, vehicle VOC emissions may actually increase given a predicted growth in total vehicle kilometers driven in a future electrified fleet and will undergo a complete VOC respeciation due to the source change.

Sources of non-methane hydrocarbons in surface air in Delhi, India.

Rapid economic growth and development have exacerbated air quality problems across India, driven by many poorly understood pollution sources and understanding their relative importance remains critical to characterising the key drivers of air pollution. A comprehensive suite of measurements of 90 non-methane hydrocarbons (NMHCs) (C2-C14), including 12 speciated monoterpenes and higher molecular weight monoaromatics, were made at an urban site in Old Delhi during the pre-monsoon (28-May to 05-Jun 2018) and post-monsoon (11 to 27-Oct 2018) seasons using dual-channel gas chromatography (DC-GC-FID) and two-dimensional gas chromatography (GC×GC-FID). Significantly higher mixing ratios of NMHCs were measured during the post-monsoon campaign, with a mean night-time enhancement of around 6. Like with NOx and CO, strong diurnal profiles were observed for all NMHCs, except isoprene, with very high NMHC mixing ratios between 35-1485 ppbv. The sum of mixing ratios of benzene, toluene, ethylbenzene and xylenes (BTEX) routinely exceeded 100 ppbv at night during the post-monsoon period, with a maximum measured mixing ratio of monoaromatic species of 370 ppbv. The mixing ratio of highly reactive monoterpenes peaked at around 6 ppbv in the post-monsoon campaign and correlated strongly with anthropogenic NMHCs, suggesting a strong non-biogenic source in Delhi. A detailed source apportionment study was conducted which included regression analysis to CO, acetylene and other NMHCs, hierarchical cluster analysis, EPA UNMIX 6.0, principal component analysis/absolute principal component scores (PCA/APCS) and comparison with NMHC ratios (benzene/toluene and i-/n-pentane) in ambient samples to liquid and solid fuels. These analyses suggested the primary source of anthropogenic NMHCs in Delhi was from traffic emissions (petrol and diesel), with average mixing ratio contributions from Unmix and PCA/APCS models of 38% from petrol, 14% from diesel and 32% from liquified petroleum gas (LPG) with a smaller contribution (16%) from solid fuel combustion. Detailed consideration of the underlying meteorology during the campaigns showed that the extreme night-time mixing ratios of NMHCs during the post-monsoon campaign were the result of emissions into a very shallow and stagnant boundary layer. The results of this study suggest that despite widespread open burning in India, traffic-related petrol and diesel emissions remain the key drivers of gas-phase urban air pollution in Delhi.

Using highly time-resolved online mass spectrometry to examine biogenic and anthropogenic contributions to organic aerosol in Beijing.

Organic aerosols, a major constituent of fine particulate mass in megacities, can be directly emitted or formed from secondary processing of biogenic and anthropogenic volatile organic compound emissions. The complexity of volatile organic compound emission sources, speciation and oxidation pathways leads to uncertainties in the key sources and chemistry leading to formation of organic aerosol in urban areas. Historically, online measurements of organic aerosol composition have been unable to resolve specific markers of volatile organic compound oxidation, while offline analysis of markers focus on a small proportion of organic aerosol and lack the time resolution to carry out detailed statistical analysis required to study the dynamic changes in aerosol sources and chemistry. Here we use data collected as part of the joint UK-China Air Pollution and Human Health (APHH-Beijing) collaboration during a field campaign in urban Beijing in the summer of 2017 alongside laboratory measurements of secondary organic aerosol from oxidation of key aromatic precursors (1,3,5-trimethyl benzene, 1,2,4-trimethyl benzene, propyl benzene, isopropyl benzene and 1-methyl naphthalene) to study the anthropogenic and biogenic contributions to organic aerosol. For the first time in Beijing, this study applies positive matrix factorisation to online measurements of organic aerosol composition from a time-of-flight iodide chemical ionisation mass spectrometer fitted with a filter inlet for gases and aerosols (FIGAERO-ToF-I-CIMS). This approach identifies the real-time variations in sources and oxidation processes influencing aerosol composition at a near-molecular level. We identify eight factors with distinct temporal variability, highlighting episodic differences in OA composition attributed to regional influences and in situ formation. These have average carbon numbers ranging from C5-C9 and can be associated with oxidation of anthropogenic aromatic hydrocarbons alongside biogenic emissions of isoprene, α-pinene and sesquiterpenes.

Single cell transcriptomes of normal endometrial derived organoids uncover novel cell type markers and cryptic differentiation of primary tumours.

Endometrial carcinoma, the most common gynaecological cancer, develops from endometrial epithelium which is composed of secretory and ciliated cells. Pathologic classification is unreliable and there is a need for prognostic tools. We used single cell sequencing to study organoid model systems derived from normal endometrial endometrium to discover novel markers specific for endometrial ciliated or secretory cells. A marker of secretory cells (MPST) and several markers of ciliated cells (FAM92B, WDR16, and DYDC2) were validated by immunohistochemistry on organoids and tissue sections. We performed single cell sequencing on endometrial and ovarian tumours and found both secretory-like and ciliated-like tumour cells. We found that ciliated cell markers (DYDC2, CTH, FOXJ1, and p73) and the secretory cell marker MPST were expressed in endometrial tumours and positively correlated with disease-specific and overall survival of endometrial cancer patients. These findings suggest that expression of differentiation markers in tumours correlates with less aggressive disease, as would be expected for tumours that retain differentiation capacity, albeit cryptic in the case of ciliated cells. These markers could be used to improve the risk stratification of endometrial cancer patients, thereby improving their management. We further assessed whether consideration of MPST expression could refine the ProMiSE molecular classification system for endometrial tumours. We found that higher expression levels of MPST could be used to refine stratification of three of the four ProMiSE molecular subgroups, and that any level of MPST expression was able to significantly refine risk stratification of the copy number high subgroup which has the worst prognosis. Taken together, this shows that single cell sequencing of putative cells of origin has the potential to uncover novel biomarkers that could be used to guide management of cancers. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Key Role of NO3 Radicals in the Production of Isoprene Nitrates and Nitrooxyorganosulfates in Beijing.

The formation of isoprene nitrates (IsN) can lead to significant secondary organic aerosol (SOA) production and they can act as reservoirs of atmospheric nitrogen oxides. In this work, we estimate the rate of production of IsN from the reactions of isoprene with OH and NO3 radicals during the summertime in Beijing. While OH dominates the loss of isoprene during the day, NO3 plays an increasingly important role in the production of IsN from the early afternoon onwards. Unusually low NO concentrations during the afternoon resulted in NO3 mixing ratios of ca. 2 pptv at approximately 15:00, which we estimate to account for around a third of the total IsN production in the gas phase. Heterogeneous uptake of IsN produces nitrooxyorganosulfates (NOS). Two mono-nitrated NOS were correlated with particulate sulfate concentrations and appear to be formed from sequential NO3 and OH oxidation. Di- and tri-nitrated isoprene-related NOS, formed from multiple NO3 oxidation steps, peaked during the night. This work highlights that NO3 chemistry can play a key role in driving biogenic-anthropogenic interactive chemistry in Beijing with respect to the formation of IsN during both the day and night.

Bariatric surgery for patients with type 2 diabetes mellitus requiring insulin: Clinical outcome and cost-effectiveness analyses.

BACKGROUND: Although bariatric surgery is well established as an effective treatment for patients with obesity and type 2 diabetes mellitus (T2DM), there exists reluctance to increase its availability for patients with severe T2DM. The aims of this study were to examine the impact of bariatric surgery on T2DM resolution in patients with obesity and T2DM requiring insulin (T2DM-Ins) using data from a national database and to develop a health economic model to evaluate the cost-effectiveness of surgery in this cohort when compared to best medical treatment (BMT). METHODS AND FINDINGS: Clinical data from the National Bariatric Surgical Registry (NBSR), a comprehensive database of bariatric surgery in the United Kingdom, were extracted to analyse outcomes of patients with obesity and T2DM-Ins who underwent primary bariatric surgery between 2009 and 2017. Outcomes for this group were combined with data sourced from a comprehensive literature review in order to develop a state-transition microsimulation model to evaluate cost-effectiveness of bariatric surgery versus BMT for patients over a 5-year time horizon. The main outcome measure for the clinical study was insulin cessation at 1-year post-surgery: relative risks (RR) summarising predictive factors were determined, unadjusted, and after adjusting for variables including age, initial body mass index (BMI), duration of T2DM, and weight loss. Main outcome measures for the economic evaluation were total costs, total quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) at willingness-to-pay threshold of GBP£20,000. A total of 2,484 patients were eligible for inclusion, of which 1,847 had 1-year follow-up data (mean age of 51 years, mean initial BMI 47.2 kg/m2, and 64% female). 67% of patients no longer required insulin at 1-year postoperatively: these rates persisted for 4 years. Roux-en-Y gastric bypass (RYGB) was associated with a higher rate of insulin cessation (71.7%) than sleeve gastrectomy (SG; 64.5%; RR 0.92, confidence interval (CI) 0.86-0.99) and adjustable gastric band (AGB; 33.6%; RR 0.45, CI 0.34-0.60; p < 0.001). When adjusted for percentage total weight loss and demographic variables, insulin cessation following surgery was comparable for RYGB and SG (RR 0.97, CI 0.90-1.04), with AGB having the lowest cessation rates (RR 0.55, CI 0.40-0.74; p < 0.001). Over 5 years, bariatric surgery was cost saving compared to BMT (total cost GBP£22,057 versus GBP£26,286 respectively, incremental difference GBP£4,229). This was due to lower treatment costs as well as reduced diabetes-related complications costs and increased health benefits. Limitations of this study include loss to follow-up of patients within the NBSR dataset and that the time horizon for the economic analysis is limited to 5 years. In addition, the study reflects current medical and surgical treatment regimens for this cohort of patients, which may change. CONCLUSIONS: In this study, we observed that in patients with obesity and T2DM-Ins, bariatric surgery was associated with high rates of postoperative cessation of insulin therapy, which is, in turn, a major driver of overall reductions in direct healthcare cost. Our findings suggest that a strategy utilising bariatric surgery for patients with obesity and T2DM-Ins is cost saving to the national healthcare provider (National Health Service (NHS)) over a 5-year time horizon.

In Vitro and In Vivo Activity, Tolerability, and Mechanism of Action of BX795 as an Antiviral against Herpes Simplex Virus 2 Genital Infection.

Herpes simplex virus type 2 (HSV-2) causes recurrent lesions in the anogenital area that may be transmitted through sexual encounters. Nucleoside analogs, such as acyclovir (ACV), are currently prescribed clinically to curb this infection. However, in some cases, reduced efficacy has been observed due to the emergence of resistance against these drugs. In our previous study, we reported the discovery of a novel anti-HSV-1 small molecule, BX795, which was originally used as an inhibitor of TANK-binding kinase 1 (TBK1). In this study, we report the antiviral efficacy of BX795 on HSV-2 infection in vaginal epithelial cells in vitro at 10 µM and in vivo at 50 µM. Additionally, through biochemical assays in vitro and histopathology in vivo, we show the tolerability of BX795 in vaginal epithelial cells at concentrations as high as 80 µM. Our investigations also revealed that the mechanism of action of BX795 antiviral activity stems from the reduction of viral protein translation via inhibition of protein kinase B phosphorylation. Finally, using a murine model of vaginal infection, we show that topical therapy using 50 µM BX795 is well tolerated and efficacious in controlling HSV-2 replication.

The (Dis)assembling of Form: Revealing the Ideas Built Into Manchester's Medical School.

This paper addresses a gap in our understanding of medical history - the architecture of medical schools - and demonstrates the ways in which architectural form can be used to better understand medical epistemology and pedagogy. It examines an instructive case study - the late-nineteenth-century medical school buildings in Manchester - and examines the concepts that were drawn together and expressed in the buildings. Through its exploration, the paper argues first, that medical schools and spaces for medical education should be given greater consideration as a significant category in the history of medical buildings. Second, that buildings such as its case study are an important source of evidence and means to understand the role of medicine in society and the ideas with which its contemporary practitioners and educators were concerned. Third, the paper argues that, to make best use of buildings as sources, we should view them as agents which have assembled divergent ideas and incorporated them into the built form. In this way, such buildings have woven into them an inventory of ideas which can be untangled using designs and physical evidence.

Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood.

BACKGROUND: The early life environment may influence susceptibility to obesity and metabolic disease in later life through epigenetic processes. SLC6A4 is an important mediator of serotonin bioavailability, and has a key role in energy balance. We tested the hypothesis that methylation of the SLC6A4 gene predicts adiposity across the life course. METHODS: DNA methylation at 5 CpGs within the SLC6A4 gene identified from a previous methyl binding domain array was measured by pyrosequencing. We measured DNA methylation in umbilical cord (UC) from children in the Southampton Women's Survey cohort (n = 680), in peripheral blood from adolescents in the Western Australian Pregnancy Cohort Study (n = 812), and in adipose tissue from lean and obese adults from the UK BIOCLAIMS cohort (n = 81). Real-time PCR was performed to assess whether there were corresponding alterations in gene expression in the adipose tissue. RESULTS: Lower UC methylation of CpG5 was associated with higher total fat mass at 4 years (p = 0.031), total fat mass at 6-7 years (p = 0.0001) and % fat mass at 6-7 years (p = 0.004). Lower UC methylation of CpG5 was also associated with higher triceps skinfold thickness at birth (p = 0.013), 6 months (p = 0.038), 12 months (p = 0.062), 2 years (p = 0.0003), 3 years (p = 0.00004) and 6-7 years (p = 0.013). Higher maternal pregnancy weight gain (p = 0.046) and lower parity (p = 0.029) were both associated with lower SLC6A4 CpG5 methylation. In adolescents, lower methylation of CpG5 in peripheral blood was associated with greater concurrent measures of adiposity including BMI (p ≤ 0.001), waist circumference (p = 0.011), subcutaneous fat (p ≤ 0.001) and subscapular, abdominal and suprailiac skinfold thicknesses (p = 0.002, p = 0.008, p = 0.004, respectively). In adipose tissue, methylation of both SLC6A4 CpG5 (p = 0.019) and expression of SLC6A4 (p = 0.008) was lower in obese compared with lean adults. CONCLUSIONS: These data suggest that altered methylation of CpG loci within SLC6A4 may provide a robust marker of adiposity across the life course.

Host Enzymes Heparanase and Cathepsin L Promote Herpes Simplex Virus 2 Release from Cells.

Herpes simplex virus 2 (HSV-2) can productively infect many different cell types of human and nonhuman origin. Here we demonstrate interconnected roles for two host enzymes, heparanase (HPSE) and cathepsin L, in HSV-2 release from cells. In vaginal epithelial cells, HSV-2 causes heparan sulfate shedding and upregulation in HPSE levels during the productive phase of infection. We also noted increased levels of cathepsin L and show that regulation of HPSE by cathepsin L via cleavage of HPSE proenzyme is important for infection. Furthermore, inhibition of HPSE by a specific inhibitor, OGT 2115, dramatically reduces HSV-2 release from vaginal epithelial cells. Likewise, we show evidence that the inhibition of cathepsin L is detrimental to the infection. The HPSE increase after infection is mediated by an increased NF-κB nuclear localization and a resultant activation of HPSE transcription. Together these mechanisms contribute to the removal of heparan sulfate from the cell surface and thus facilitate virus release from cells.IMPORTANCE Genital infections by HSV-2 represent one of the most common sexually transmitted viral infections. The virus causes painful lesions and sores around the genitals or rectum. Intermittent release of the virus from infected tissues during sexual activities is the most common cause of transmission. At the molecular level, cell surface heparan sulfate (HS) is known to provide attachment sites for HSV-2. While the removal of HS during HSV-1 release has been shown, not much is known about the host factors and their regulators that contribute to HSV-2 release from natural target cell types. Here we suggest a role for the host enzyme heparanase in HSV-2 release. Our work reveals that in addition to the regulation of transcription by NF-κB, HPSE is also regulated posttranslationally by cathepsin L and that inhibition of heparanase activity directly affects HSV-2 release. We provide unique insights into the host mechanisms controlling HSV-2 egress and spread.

Herpes Simplex Virus 1 Infection Promotes the Growth of a Subpopulation of Tumor Cells in Three-Dimensional Uveal Melanoma Cultures.

Herpes simplex virus 1 (HSV-1)-mediated oncolytic therapy is an emerging cancer treatment modality with potential effectiveness against a variety of malignancies. To better understand the interaction of HSV-1 with neoplastic cells, we inoculated three-dimensional (3D) cultures of human uveal melanoma cells with HSV-1. 3D melanoma cultures were established by placing tumor cells on the surface of a Matrigel matrix, which was followed by the growth of tumor cells on the matrix surface and invasion of the Matrigel matrix by some tumor cells to form multicellular tumor spheroids within the matrix. When established 3D melanoma cultures were inoculated with HSV-1 by placing virus on the surface of cultures, virus infection caused extensive death of melanoma cells growing on the surface of the 3D matrix and significantly decreased the number of tumor cell spheroids within the matrix. However, HSV-1 infection did not lead to a complete destruction of tumor cells in the 3D cultures during a 17-day observation period and, surprisingly, HSV-1 infection promoted the growth of some melanoma cells within the matrix as determined by the significantly increased size of residual viable multicellular tumor spheroids in virus-inoculated 3D cultures at 17 days after virus inoculation. Acyclovir treatment inhibited HSV-1-induced tumor cell killing but did not block the virus infection-induced increase in spheroid size. These findings suggest that although HSV-1 oncolytic virotherapy may cause extensive tumor cell killing, it may also be associated with the unintended promotion of the growth of some tumor cells.IMPORTANCE Cancer cells are exposed to HSV-1 during oncolytic virotherapy with the intention of killing tumor cells. Our observations reported here suggest that potential dangers of HSV-1 oncolytic therapy include promotion of growth of some tumor cells. Furthermore, our findings raise the possibility that HSV-1 infection of neoplastic cells during natural infections or vaccinations may promote the growth of tumors. Our study indicates that HSV-1 infection of 3D tumor cell cultures provides an experimental platform in which mechanisms of HSV-1-mediated promotion of tumor cell growth can be effectively studied.

A Core Outcome Set for the Benefits and Adverse Events of Bariatric and Metabolic Surgery: The BARIACT Project.

BACKGROUND: Bariatric and metabolic surgery is used as a treatment for patients with severe and complex obesity. However, there is a need to improve outcome selection and reporting in bariatric surgery trials. A Core Outcome Set (COS), an agreed minimum set of outcomes reported in all studies of a specific condition, may achieve this. Here, we present the development of a COS for BARIAtric and metabolic surgery Clinical Trials-the BARIACT Study. METHODS AND FINDINGS: Outcomes identified from systematic reviews and patient interviews informed a questionnaire survey. Patients and health professionals were surveyed three times and asked to rate the importance of each item on a 1-9 scale. Delphi methods provided anonymised feedback to participants. Items not meeting predefined criteria were discarded between rounds. Remaining items were discussed at consensus meetings, held separately with patients and professionals, where the COS was agreed. Data sources identified 2,990 outcomes, which were used to develop a 130-item questionnaire. Round 1 response rates were moderate but subsequently improved to above 75% for other rounds. After rounds 2 and 3, 81 and 14 items were discarded, respectively, leaving 35 items for discussion at consensus meetings. The final COS included nine items: "weight," "diabetes status," "cardiovascular risk," "overall quality of life (QOL)," "mortality," "technical complications of the specific operation," "any re-operation/re-intervention," "dysphagia/regurgitation," and "micronutrient status." The main limitation of this study was that it was based in the United Kingdom only. CONCLUSIONS: The COS is recommended to be used as a minimum in all trials of bariatric and metabolic surgery. Adoption of the COS will improve data synthesis and the value of research data. Future work will establish methods for the measurement of the outcomes in the COS.

What are important outcomes of bariatric surgery? An in-depth analysis to inform the development of a core outcome set and a comparison between the views of surgeons and other health professionals (the BARIACT study).

BACKGROUND: Outcome reporting in bariatric surgery needs uniformity. A core outcome set is an agreed minimum set of outcomes reported in all studies of a particular condition, but members of the bariatric multidisciplinary team might value outcomes differently. The aim of this study was to summarise existing outcome reporting in bariatric surgery, to inform the development of a core outcome set, and to compare outcomes selected as important by type of health professional. METHODS: Outcomes reported in randomised controlled trials (RCTs) and large non-randomised studies, identified by a systematic review, were listed verbatim. Frequency of outcome reporting and uniformity of definition were assessed. A questionnaire to rate the importance of each outcome was completed by members of the bariatric multidisciplinary team. Responses to each item were scored as 1 (not essential) to 9 (absolutely essential). We ranked outcomes according to percentage deemed important (7-9) and according to respondents by type of health professional. FINDINGS: We identified 1088 individual outcomes from 90 studies (39 RCTs), grouped them into health domains, and presented them as a questionnaire with 131 items to 489 multidisciplinary team members. Most outcomes (n=920, 85%) were reported only once. The largest outcome domain was surgical complications, and 432 outcomes (42%) corresponded to an adverse event. Only a quarter of outcomes (n=461) were defined, and were often contradictory. For questionnaire responders (n=164, response rate 33·5%), most were surgeons (n=80, 48·8%), followed by dietitians (n=31, 18·9%), nurses (n=24, 14·6%), physicians (n=12, 7·3%), and others (n=16, 9·9%). Improvement in diabetes was the top outcome for all health professionals. Seven of the surgeon's top ten outcomes were adverse events, compared with three for other health professionals. Groups valued a measure of weight differently (third vs 15th for other health professionals and surgeons, respectively). INTERPRETATION: This study shows that the assessment of bariatric surgery focuses largely on adverse events and resolution of comorbidity, but that reporting is inconsistent and ill-defined. Substantial variation between the views of surgeons and those of other health professionals was evident. The next step is to provide feedback to participants and to survey their views again before a final consensus meeting to produce a core outcome set for the Benefits and Adverse events in BARIAtric surgery Clinical Trials (BARIACT) as a solution to this problem. FUNDING: National Institute for Health Research (NIHR), and the NIHR Health Technology Assessment programme. This work was also undertaken with the support of the MRC ConDuCT-II Hub (Collaboration and innovation for Difficult and Complex randomised controlled Trials In Invasive procedures, MR/K025643/1).

The use of adjustable gastric bands for management of severe and complex obesity.

BACKGROUND: Obesity levels in the UK have reached a sustained high and ∼4% of the population would be candidates for bariatric surgery based upon current UK NICE guidelines, which has important implications for Clinical Commissioning Groups. SOURCES OF DATA: Summary data from Cochrane systematic reviews, randomized controlled trials (RCTs) and cohort studies. AREAS OF AGREEMENT: Currently, the only treatment that offers significant and durable weight loss for those with severe and complex obesity is surgery. Three operations account for 95% of all bariatric surgery in the UK, but the NHS offers surgery to only a small fraction of those who could benefit. Laparoscopic adjustable gastric banding (gastric banding) has potentially the lowest risk and up-front costs of the three procedures. AREAS OF CONTROVERSY: Reliable Level 1 evidence of the relative effectiveness of the operations is lacking. GROWING POINTS: As a point intervention, weight loss surgery together with the chronic disease management strategy for obesity can prevent significant future disease and mortality, and the NHS should embrace both. AREAS TIMELY FOR DEVELOPING RESEARCH: Better RCT evidence is needed including clinical effectiveness and economic analysis to answer the important question 'which is the best of the three operations most frequently performed?' This review considers the current evidence for gastric banding for the treatment of severe and complex obesity.

Atmospheric ethanol in London and the potential impacts of future fuel formulations.

There is growing global consumption of non-fossil fuels such as ethanol made from renewable biomass. Previous studies have shown that one of the main air quality disadvantages of using ethanol blended fuels is a significant increase in the production of acetaldehyde, an unregulated and toxic pollutant. Most studies on the impacts of ethanol blended gasoline have been carried out in the US and Brazil, with much less focus on the UK and Europe. We report time resolved measurements of ethanol in London during the winter and summer of 2012. In both seasons the mean mixing ratio of ethanol was around 5 ppb, with maximum values over 30 ppb, making ethanol currently the most abundant VOC in London air. We identify a road transport related source, with 'rush-hour' peaks observed. Ethanol is strongly correlated with other road transport-related emissions, such as small aromatics and light alkanes, and has no relationship to summer biogenic emissions. To determine the impact of road transport-related ethanol emission on secondary species (i.e. acetaldehyde and ozone), we use both a chemically detailed box model (incorporating the Master Chemical Mechanism, MCM) and a global and nested regional scale chemical transport model (GEOS-Chem), on various processing time scales. Using the MCM model, only 16% of the modelled acetaldehyde was formed from ethanol oxidation. However, the model significantly underpredicts the total levels of acetaldehyde, indicating a missing primary emission source, that appears to be traffic-related. Further support for a primary emission source comes from the regional scale model simulations, where the observed concentrations of ethanol and acetaldehyde can only be reconciled with the inclusion of large primary emissions. Although only constrained by one set of observations, the regional modelling suggests a European ethanol source similar in magnitude to that of ethane (∼60 Gg per year) and greater than that of acetaldehyde (∼10 Gg per year). The increased concentrations of ethanol and acetaldehyde from primary emissions impacts both radical and NOx cycling over Europe, resulting in significant regional impacts on NOy speciation and O3 concentrations, with potential changes to human exposure to air pollutants.

Successful Percutaneous Transcatheter Patent Foramen Ovale Closure Through The Right Internal Jugular Vein Using Stiff Amplatzer Catheter With A Reshaped Tip.

Percutaneous transcatheter closure of a patent foramen ovale (PFO) remains challenging when femoral venous approach is not available. We describe the successful closure of a PFO using the right internal jugular venous approach and a catheter delivery system with a reshaped tip in a patient with a PFO, recurrent stroke, recurrent gastrointestinal bleeding, bilateral deep venous thrombosis and thrombosed bilateral inferior vena cava filter.

Extensive halogen-mediated ozone destruction over the tropical Atlantic Ocean.

Increasing tropospheric ozone levels over the past 150 years have led to a significant climate perturbation; the prediction of future trends in tropospheric ozone will require a full understanding of both its precursor emissions and its destruction processes. A large proportion of tropospheric ozone loss occurs in the tropical marine boundary layer and is thought to be driven primarily by high ozone photolysis rates in the presence of high concentrations of water vapour. A further reduction in the tropospheric ozone burden through bromine and iodine emitted from open-ocean marine sources has been postulated by numerical models, but thus far has not been verified by observations. Here we report eight months of spectroscopic measurements at the Cape Verde Observatory indicative of the ubiquitous daytime presence of bromine monoxide and iodine monoxide in the tropical marine boundary layer. A year-round data set of co-located in situ surface trace gas measurements made in conjunction with low-level aircraft observations shows that the mean daily observed ozone loss is approximately 50 per cent greater than that simulated by a global chemistry model using a classical photochemistry scheme that excludes halogen chemistry. We perform box model calculations that indicate that the observed halogen concentrations induce the extra ozone loss required for the models to match observations. Our results show that halogen chemistry has a significant and extensive influence on photochemical ozone loss in the tropical Atlantic Ocean boundary layer. The omission of halogen sources and their chemistry in atmospheric models may lead to significant errors in calculations of global ozone budgets, tropospheric oxidizing capacity and methane oxidation rates, both historically and in the future.

Socially responsible mining: the relationship between mining and poverty, human health and the environment.

Increasing global demand for metals is putting strain on the ability of the mining industry to physically keep up with demand (physical scarcity). Conversely, social issues including the environmental and human health consequences of mining as well as the disparity in income distribution from mining revenues are disproportionately felt at the local community level. This has created social rifts, particularly in the developing world, between affected communities and both industry and governments. Such rifts can result in a disruption of the steady supply of metals (situational scarcity). Here we discuss the importance of mining in relationship to poverty, identify steps that have been taken to create a framework for socially responsible mining, and then discuss the need for academia to work in partnership with communities, government, and industry to develop transdisciplinary research-based step change solutions to the intertwined problems of physical and situational scarcity.

Evaluating drug stability and sterility in single-dose vials when accessed with a closed system transfer device.

Background: Impact of drug wastage is a legitimate and persistent concern. Financial impact of drug waste is borne by the hospital network, patients, and healthcare systems. Measures to reduce drug wastage may have a positive impact throughout healthcare systems. Objective: This study investigated the stability and sterility of single-dose vials when repeatedly accessed with a closed system transfer device. By evaluating the sterility and stability, these results may be used to validate the extension of vial usage and lead to potential drug wastage reduction. Methods: Sterility testing was performed in accordance with US Pharmacopeia 71. A closed system transfer device was incorporated into simulated compounding tasks, utilizing growth media. Simulated compounding tasks were performed in the clinical environment, followed by incubation to stimulate growth. Stability testing was performed in accordance with US Pharmacopeia monographs at multiple timepoints post access. Test samples were comparatively tested via high-performance liquid chromatography to freshly opened vials at each timepoint. Results: No growth was observed in test samples. Control vials displayed growth, where appropriate. The drugs retained stability, when compared to freshly opened vials at 0, 24, 48, and 72 h, post access. Conclusions: This study confirms that closed system transfer devices do not contribute to microbial contamination of drug vials, following the repeated access, for up to 7 days and the tested drugs retained equivalent chemical stability for up to 72 h post access. This study may offer a manner by which a facility may assess single-dose vials' sterility and stability, following repeated access by a closed system transfer device.