In contrast to traditional static cold preservation of donor livers, normothermic machine perfusion may reduce preservation injury, improve graft viability and potentially allows ex vivo assessment ...of graft viability before transplantation. We have studied the feasibility of normothermic machine perfusion in four discarded human donor livers. Normothermic machine perfusion consisted of pressure and temperature controlled pulsatile perfusion of the hepatic artery and continuous portal perfusion for 6 h. Two hollow fiber membrane oxygenators provided oxygenation of the perfusion fluid. Biochemical markers in the perfusion fluid reflected minimal hepatic injury and improving function. Lactate levels decreased to normal values, reflecting active metabolism by the liver (mean lactate 10.0 ± 2.3 mmol/L at 30 min to 2.3 ± 1.2 mmol/L at 6 h). Bile production was observed throughout the 6 h perfusion period (mean rate 8.16 ± 0.65 g/h after the first hour). Histological examination before and after 6 h of perfusion showed well‐preserved liver morphology without signs of additional hepatocellular ischemia, biliary injury or sinusoidal damage. In conclusion, this study shows that normothermic machine perfusion of human donor livers is technically feasible. It allows assessment of graft viability before transplantation, which opens new avenues for organ selection, therapeutic interventions and preconditioning.
This study demonstrates the technical feasibility of normothermic machine perfusion of human donor livers.
A gap in emission inventories of urban volatile organic compound (VOC) sources, which contribute to regional ozone and aerosol burdens, has increased as transportation emissions in the United States ...and Europe have declined rapidly. A detailed mass balance demonstrates that the use of volatile chemical products (VCPs)-including pesticides, coatings, printing inks, adhesives, cleaning agents, and personal care products-now constitutes half of fossil fuel VOC emissions in industrialized cities. The high fraction of VCP emissions is consistent with observed urban outdoor and indoor air measurements. We show that human exposure to carbonaceous aerosols of fossil origin is transitioning away from transportation-related sources and toward VCPs. Existing U.S. regulations on VCPs emphasize mitigating ozone and air toxics, but they currently exempt many chemicals that lead to secondary organic aerosols.
Although significant progress has been made in understanding the sources and chemistry of indoor volatile organic compounds (VOCs) during the past decades, much is unknown about the role of humans in ...indoor air chemistry. In the spring of 2014, we conducted continuous measurements of VOCs using a proton transfer reaction mass spectrometer (PTR‐MS) in a university classroom. Positive matrix factorization (PMF) of the measured VOCs revealed a ‘human influence’ component, which likely represented VOCs produced from human breath and ozonolysis of human skin lipids. The concentration of the human influence component increased with the number of occupants and decreased with ventilation rate in a similar way to CO2, with an average contribution of 40% to the measured daytime VOC concentration. In addition, the human skin lipid ozonolysis products were observed to correlate with CO2 and anticorrelate with O3, suggesting that reactions on human surfaces may be important sources of indoor VOCs and sinks for indoor O3. Our study suggests that humans can substantially affect VOC composition and oxidative capacity in indoor environments.
Up to 32% of patients with esophageal cancer show a pathological complete response (ypCR) after neoadjuvant therapy. To prevent overtreatment, the indication to perform esophagectomy in these ...patients should be reconsidered. Implementing an organ-preserving strategy for patients with ypCR requires an accurate assessment of residual disease after neoadjuvant treatment. The aim of this study was to systematically review the effectiveness of imaging techniques used for detection of ypCR after neoadjuvant therapy but before resection in patients with esophageal cancer.
A systematic literature search of the Medline, Embase, and Cochrane Library databases was performed from January 1, 2000, to December 13, 2017. Eligible studies were diagnostic studies that compared results of imaging modalities after neoadjuvant therapy to histopathological findings in the resection specimen after esophagectomy. Methodological quality was assessed by the Cochrane Quality Assessment of Diagnostic Accuracy Studies, version 2, model. Primary outcome measures were true positive, false-positive, false-negative, and true negative values of imaging techniques predicting ypCR. A meta-analysis was performed by pooling sensitivities and specificities by using a bivariate model.
A total of 4420 articles were identified. After exclusion of irrelevant titles and abstracts, 360 articles were reviewed in full text. In total, four imaging modalities (computed tomography CT, positron emission tomography PET-CT, endoscopic ultrasound EUS, and magnetic resonance imaging MRI) were used for restaging. The meta-analysis was conducted with data from 56 studies involving 3625 patients. The pooled sensitivities of CT, PET-CT, EUS, and MRI for detecting ypCR were 0.35, 0.62, 0.01 and 0.80, respectively, whereas the pooled specificities were 0.83, 0.73, 0.99, and 0.83, respectively. The positive predictive value in detecting ypCR was 0.47 for CT, 0.41 for PET-CT, not applicable for EUS, and 0.61 for MRI.
Current imaging modalities such as CT, PET-CT, and EUS seem to be insufficiently accurate to identify complete responders. More accurate diagnostic tests are needed to improve restaging accuracy for patients with esophageal cancer.
A new secondary organic aerosol (SOA) parameterization based on the volatility basis set is implemented in a regional air quality model WRF‐CHEM. Full meteorological and chemistry simulations are ...carried out for the United States for August–September 2006. Predicted organic aerosol (OA) concentrations are compared against surface measurements made by several networks and aircraft data from the TexAQS‐2006 field campaign. Elemental carbon simulations are also evaluated in order to evaluate the model's ability to capture their emissions, transport, and removal. Certain measurement limitations, such as daily averaged OA concentrations, impose some difficulties on the model evaluation, and hourly averaged OA measurements provide more informative constraints compared to daily concentrations. The updated model demonstrates a significant improvement in simulating the OA concentrations compared to the standard WRF‐CHEM, which predicts very little SOA. The improvement in organic carbon (OC) predictions is noticeable in correlations and model bias. The correlations of OC exceed that of the persistence forecasts for hourly concentrations in the southeast United States during daytime. The updated traditional SOA yields still lead to an underestimation of observed OA, while addition of the multigenerational volatile organic compound (VOC) oxidation drastically improves model performance. However, several key uncertainties remain in SOA formation and loss mechanisms, which are characterized through several perturbation simulations. Dry deposition of VOC oxidation products is an important factor in the atmospheric SOA budget. The combination of the biogenic VOC emissions, updated SOA yields, and aging mechanism result in biogenic SOA being the dominant OA component for much of the nonurban United States.
Key Points
VBS approach to secondary organic aerosol formation within WRF‐CHEM
Evaluation using surface and aircraft data
Organic aerosol modeling for the continental United States
Measurements of hydroxyl (OH) and hydroperoxy (HO2*) radical concentrations were made at the Pasadena ground site during the CalNex‐LA 2010 campaign using the laser‐induced fluorescence‐fluorescence ...assay by gas expansion technique. The measured concentrations of OH and HO2* exhibited a distinct weekend effect, with higher radical concentrations observed on the weekends corresponding to lower levels of nitrogen oxides (NOx). The radical measurements were compared to results from a zero‐dimensional model using the Regional Atmospheric Chemical Mechanism‐2 constrained by NOx and other measured trace gases. The chemical model overpredicted measured OH concentrations during the weekends by a factor of approximately 1.4 ± 0.3 (1σ), but the agreement was better during the weekdays (ratio of 1.0 ± 0.2). Model predicted HO2* concentrations underpredicted by a factor of 1.3 ± 0.2 on the weekends, while measured weekday concentrations were underpredicted by a factor of 3.0 ± 0.5. However, increasing the modeled OH reactivity to match the measured total OH reactivity improved the overall agreement for both OH and HO2* on all days. A radical budget analysis suggests that photolysis of carbonyls and formaldehyde together accounted for approximately 40% of radical initiation with photolysis of nitrous acid accounting for 30% at the measurement height and ozone photolysis contributing less than 20%. An analysis of the ozone production sensitivity reveals that during the week, ozone production was limited by volatile organic compounds throughout the day during the campaign but NOx limited during the afternoon on the weekends.
Key Points
Measurements of OH and HO2 during CalNex‐LA displayed a weekend effect
Modeled OH and HO2 agreed with measurements after accounting for missing OH reactivity
Ozone production was VOC limited on the weekdays but NOx limited on the weekends
Proton-transfer-reaction mass spectrometry (PTR-MS) has been widely used to study the emissions, distributions, and chemical evolution of volatile organic compounds (VOCs) in the atmosphere. The ...applications of PTR-MS have greatly promoted understanding of VOC sources and their roles in air-quality issues. In the past two decades, many new mass spectrometric techniques have been applied in PTR-MS instruments, and the performance of PTR-MS has improved significantly. This Review summarizes these developments and recent applications of PTR-MS in the atmospheric sciences. We discuss the latest instrument development and characterization work on PTR-MS instruments, including the use of time-of-flight mass analyzers and new types of ion guiding interfaces. Here we review what has been learned about the specificity of different product ion signals for important atmospheric VOCs. We present some of the recent highlights of VOC research using PTR-MS including new observations in urban air, biomass-burning plumes, forested regions, oil and natural gas production regions, agricultural facilities, the marine environment, laboratory studies, and indoor air. Finally, we will summarize some further instrument developments that are aimed at improving the sensitivity and specificity of PTR-MS and extending its use to other applications in atmospheric sciences, e.g., aerosol measurements and OH reactivity measurements.
White matter hyperintensities (WMH), lacunes and microbleeds are regarded as typical MRI expressions of cerebral small vessel disease (SVD) and they are highly prevalent in the elderly. However, ...clinical expression of MRI defined SVD is generally moderate and heterogeneous. By reviewing studies that directly correlated postmortem MRI and histopathology, this paper aimed to characterise the pathological substrates of SVD in order to create more understanding as to its heterogeneous clinical manifestation.
Postmortem studies showed that WMH are also heterogeneous in terms of histopathology. Damage to the tissue ranges from slight disentanglement of the matrix to varying degrees of myelin and axonal loss. Glial cell responses include astrocytic reactions--for example, astrogliosis and clasmatodendrosis--as well as loss of oligodendrocytes and distinct microglial responses. Lipohyalinosis, arteriosclerosis, vessel wall leakage and collagen deposition in venular walls are recognised microvascular changes. Suggested pathogenetic mechanisms are ischaemia/hypoxia, hypoperfusion due to altered cerebrovascular autoregulation, blood-brain barrier leakage, inflammation, degeneration and amyloid angiopathy. Only a few postmortem MRI studies have addressed lacunes and microbleeds to date. Cortical microinfarcts and changes in the normal appearing white matter are 'invisible' on conventional MRI but are nevertheless expected to contribute substantially to clinical symptoms.
Pathological substrates of WMH are heterogeneous in nature and severity, which may partly explain the weak clinicoradiological associations found in SVD. Lacunes and microbleeds have been relatively understudied and need to be further investigated. Future studies should also take into account 'MRI invisible' SVD features and consider the use of, for example, quantitative MRI techniques, to increase the sensitivity of MRI for these abnormalities and study their effects on clinical functioning.
Ground‐based and airborne volatile organic compound (VOC) measurements in Los Angeles, California, and Paris, France, during the Research at the Nexus of Air Quality and Climate Change (CalNex) and ...Megacities: Emissions, Urban, Regional and Global Atmospheric Pollution and Climate Effects, and Integrated Tools for Assessment and Mitigation (MEGAPOLI) campaigns, respectively, are used to examine the spatial variability of the composition of anthropogenic VOC urban emissions and to evaluate regional emission inventories. Two independent methods that take into account the effect of chemistry were used to determine the emission ratios of anthropogenic VOCs (including anthropogenic isoprene and oxygenated VOCs) over carbon monoxide (CO) and acetylene. Emission ratios from both methods agree within ±20%, showing the reliability of our approach. Emission ratios for alkenes, alkanes, and benzene are fairly similar between Los Angeles and Paris, whereas the emission ratios for C7–C9 aromatics in Paris are higher than in Los Angeles and other French and European Union urban areas by a factor of 2–3. The results suggest that the emissions of gasoline‐powered vehicles still dominate the hydrocarbon distribution in northern mid‐latitude urban areas, which disagrees with emission inventories. However, regional characteristics like the gasoline composition could affect the composition of hydrocarbon emissions. The observed emission ratios show large discrepancies by a factor of 2–4 (alkanes and oxygenated VOC) with the ones derived from four reference emission databases. A bias in CO emissions was also evident for both megacities. Nevertheless, the difference between measurements and inventory in terms of the overall OH reactivity is, in general, lower than 40%, and the potential to form secondary organic aerosols (SOA) agrees within 30% when considering volatile organic emissions as the main SOA precursors.
Key PointsUrban VOC emission ratios are compared in two modern megacitiesGasoline‐powered vehicles emissions are still the dominant VOC urban sourceObservations/inventory differences are <40% in terms of OH‐reactvity and SOAP
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