Calf rEF: Impact of Calf Muscle Pump Dysfunction With Reduced Ejection Fraction on All-Cause Mortality.

OBJECTIVE: To evaluate mortality outcomes by varying degrees of reduced calf muscle pump (CMP) ejection fraction (EF). PATIENTS AND METHODS: Consecutive adult patients who underwent venous air plethysmography testing at the Mayo Clinic Gonda Vascular Laboratory (January 1, 2012, through December 31, 2022) were divided into groups based on CMP EF for the assessment of all-cause mortality. Other venous physiology included measures of valvular incompetence and clinical venous disease (CEAP [clinical presentation, etiology, anatomy, and pathophysiology] score). Mortality rates were calculated using the Kaplan-Meier method. RESULTS: During the study, 5913 patients met the inclusion criteria. During 2.84-year median follow-up, there were 431 deaths. Mortality rates increased with decreasing CMP EF. Compared with EF of 50% or higher, the hazard ratios (95% CIs) for mortality were as follows: EF of 40% to 49%, 1.4 (1.0 to 2.0); EF of 30% to 39%, 1.6 (1.2 to 2.4); EF of 20% to 29%, 1.7 (1.2 to 2.4); EF of 10% to 19%, 2.4 (1.7 to 3.3) (log-rank P≤.001). Although measures of venous valvular incompetence did not independently predict outcomes, venous disease severity assessed by CEAP score was predictive. After adjusting for several clinical covariates, both CMP EF and clinical venous disease severity assessed by CEAP score remained independent predictors of mortality. CONCLUSION: Mortality rates are higher in patients with reduced CMP EF and seem to increase with each 10% decrement in CMP EF. The mortality mechanism does not seem to be impacted by venous valvular incompetence and may represent variables intrinsic to muscular physiology.

An emergent constraint on the thermal sensitivity of photosynthesis and greenness in the high latitude northern forests.

Despite the general consensus that the warming over the high latitudes northern forests (HLNF) has led to enhanced photosynthetic activity and contributed to the greening trend, isolating the impact of temperature increase on photosynthesis and greenness has been difficult due to the concurring influence of the CO2 fertilization effect. Here, using an ensemble of simulations from biogeochemical models that have contributed to the Trends in Net Land Atmosphere Carbon Exchange project (TRENDY), we identify an emergent relationship between the simulation of the climate-driven temporal changes in both gross primary productivity (GPP) and greenness (Leaf Area Index, LAI) and the model's spatial sensitivity of these quantities to growing-season (GS) temperature. Combined with spatially-resolved observations of LAI and GPP, we estimate that GS-LAI and GS-GPP increase by 17.0 ± 2.4% and 24.0 ± 3.0% per degree of warming, respectively. The observationally-derived sensitivities of LAI and GPP to temperature are about 40% and 71% higher, respectively, than the mean of the ensemble of simulations from TRENDY, primarily due to the model underestimation of the sensitivity of light use efficiency to temperature. We estimate that the regional mean GS-GPP increased 28.2 ± 5.1% between 1983-1986 and 2013-2016, much larger than the 5.8 ± 1.4% increase from the CO2 fertilization effect implied by Wenzel et al. This suggests that warming, not CO2 fertilization, is primarily responsible for the observed dramatic changes in the HLNF biosphere over the last century.

Reduced calf muscle pump function is not explained by handgrip strength measurements.

OBJECTIVE: Reduced calf muscle pump function (CPF) is an independent risk factor for venous thromboembolism and mortality. We aimed to evaluate the relationship between handgrip strength (HGS) and CPF. METHODS: Patients referred to the Gonda Vascular Laboratory for noninvasive venous studies were identified and consented. Patients underwent standard venous air plethysmography protocol. CPF (ejection fraction) was measured in each lower extremity of ambulatory patients by comparing refill volume after ankle flexes and passive refill volumes. The cutoff for reduced CPF (rCPF) was defined as an ejection fraction of <45%. Maximum HGS bilaterally was obtained (three trials per hand) using a dynamometer. HGS and CPF were compared (right hand to calf, left hand to calf) and the correlation between the measures was evaluated. RESULTS: 115 patients (mean age, 59.2 ± 17.4 years; 67 females, mean body mass index, 30.83 ± 6.46) were consented and assessed for HGS and CPF. rCPF was observed in 53 right legs (46%) and 67 left legs (58%). CPF was reduced bilaterally in 45 (39%) and unilaterally in 30 (26%) patients. HGS was reduced bilaterally in 74 (64.3%), unilaterally in 23 (20%), and normal in 18 (15.7%) patients. Comparing each hand/calf pair, no significant correlations were seen between HGS and CPF. The Spearman's rank correlation coefficients test yielded values of 0.16 for the right side and 0.10 for the left side. CONCLUSIONS: There is no significant correlation between HGS and CPF, demonstrating that HGS measurements are not an acceptable surrogate for rCPF, indicating different pathophysiological mechanisms for each process.

Artificial intelligence of arterial Doppler waveforms to predict major adverse outcomes among patients with diabetes mellitus.

OBJECTIVE: Patients with diabetes mellitus (DM) are at increased risk for peripheral artery disease (PAD) and its complications. Arterial calcification and non-compressibility may limit test interpretation in this population. Developing tools capable of identifying PAD and predicting major adverse cardiac event (MACE) and limb event (MALE) outcomes among patients with DM would be clinically useful. Deep neural network analysis of resting Doppler arterial waveforms was used to detect PAD among patients with DM and to identify those at greatest risk for major adverse outcome events. METHODS: Consecutive patients with DM undergoing lower limb arterial testing (April 1, 2015-December 30, 2020) were randomly allocated to training, validation, and testing subsets (60%, 20%, and 20%). Deep neural networks were trained on resting posterior tibial arterial Doppler waveforms to predict all-cause mortality, MACE, and MALE at 5 years using quartiles based on the distribution of the prediction score. RESULTS: Among 11,384 total patients, 4211 patients with DM met study criteria (mean age, 68.6 ± 11.9 years; 32.0% female). After allocating the training and validation subsets, the final test subset included 856 patients. During follow-up, there were 262 deaths, 319 MACE, and 99 MALE. Patients in the upper quartile of prediction based on deep neural network analysis of the posterior tibial artery waveform provided independent prediction of death (hazard ratio [HR], 3.58; 95% confidence interval [CI], 2.31-5.56), MACE (HR, 2.06; 95% CI, 1.49-2.91), and MALE (HR, 13.50; 95% CI, 5.83-31.27). CONCLUSIONS: An artificial intelligence enabled analysis of a resting Doppler arterial waveform permits identification of major adverse outcomes including all-cause mortality, MACE, and MALE among patients with DM.

Artificial Intelligence of Arterial Doppler Waveforms to Predict Major Adverse Outcomes Among Patients Evaluated for Peripheral Artery Disease.

BACKGROUND: Patients with peripheral artery disease are at increased risk for major adverse cardiac events, major adverse limb events, and all-cause death. Developing tools capable of identifying those patients with peripheral artery disease at greatest risk for major adverse events is the first step for outcome prevention. This study aimed to determine whether computer-assisted analysis of a resting Doppler waveform using deep neural networks can accurately identify patients with peripheral artery disease at greatest risk for adverse outcome events. METHODS AND RESULTS: Consecutive patients (April 1, 2015, to December 31, 2020) undergoing ankle-brachial index testing were included. Patients were randomly allocated to training, validation, and testing subsets (60%/20%/20%). Deep neural networks were trained on resting posterior tibial arterial Doppler waveforms to predict major adverse cardiac events, major adverse limb events, and all-cause death at 5 years. Patients were then analyzed in groups based on the quartiles of each prediction score in the training set. Among 11 384 total patients, 10 437 patients met study inclusion criteria (mean age, 65.8±14.8 years; 40.6% women). The test subset included 2084 patients. During 5 years of follow-up, there were 447 deaths, 585 major adverse cardiac events, and 161 MALE events. After adjusting for age, sex, and Charlson comorbidity index, deep neural network analysis of the posterior tibial artery waveform provided independent prediction of death (hazard ratio [HR], 2.44 [95% CI, 1.78-3.34]), major adverse cardiac events (HR, 1.97 [95% CI, 1.49-2.61]), and major adverse limb events (HR, 11.03 [95% CI, 5.43-22.39]) at 5 years. CONCLUSIONS: An artificial intelligence-enabled analysis of Doppler arterial waveforms enables identification of major adverse outcomes among patients with peripheral artery disease, which may promote early adoption and adherence of risk factor modification.

Particle-phase accretion forms dimer esters in pinene secondary organic aerosol.

Secondary organic aerosol (SOA) is ubiquitous in the atmosphere and plays a pivotal role in climate, air quality, and health. The production of low-volatility dimeric compounds through accretion reactions is a key aspect of SOA formation. However, despite extensive study, the structures and thus the formation mechanisms of dimers in SOA remain largely uncharacterized. In this work, we elucidate the structures of several major dimer esters in SOA from ozonolysis of α-pinene and ß-pinene-substantial global SOA sources-through independent synthesis of authentic standards. We show that these dimer esters are formed in the particle phase and propose a mechanism of nucleophilic addition of alcohols to a cyclic acylperoxyhemiacetal. This chemistry likely represents a general pathway to dimeric compounds in ambient SOA.

Methane Emissions from Dairy Operations in California's San Joaquin Valley Evaluated Using Airborne Flux Measurements.

State inventories indicate that dairy operations account for nearly half of California's methane budget. Recent analyses suggest, however, that these emissions may be underestimated, complicating efforts to develop emission reduction strategies. Here, we report estimates of dairy methane emissions in the southern San Joaquin Valley (SJV) of California in June 2021 using airborne flux measurements. We find average dairy methane fluxes of 512 ± 178 mg m-2 h-1 from a region of 300+ dairies near Visalia, CA using a combination of eddy covariance and mass balance-based techniques, corresponding to 118 ± 41 kg dairy-1 h-1. These values estimated during our June campaign are 39 ± 48% larger than annual average estimates from the recently developed VISTA-CA inventory. We observed notable increases in emissions with temperature. Our estimates align well with inventory predictions when parametrizations for the temperature dependence of emissions are applied. Our measurements further demonstrate that the VISTA-CA emission inventory is considerably more accurate than the EPA GHG-I inventory in this region. Source apportionment analyses confirm that dairy operations produce the majority of methane emissions in the southern SJV (∼65%). Fugitive oil and gas (O&G) sources account for the remaining ∼35%. Our results support the accuracy of the process-based models used to develop dairy emission inventories and highlight the need for additional investigation of the meteorological dependence of these emissions.

Atmospheric Photo-Oxidation of 2-Ethoxyethanol: Autoxidation Chemistry of Glycol Ethers.

We investigate the gas-phase photo-oxidation of 2-ethoxyethanol (2-EE) initiated by the OH radical with a focus on its autoxidation pathways. Gas-phase autoxidation─intramolecular H-shifts followed by O2 addition─has recently been recognized as a major atmospheric chemical pathway that leads to the formation of highly oxygenated organic molecules (HOMs), which are important precursors for secondary organic aerosols (SOAs). Here, we examine the gas-phase oxidation pathways of 2-EE, a model compound for glycol ethers, an important class of volatile organic compounds (VOCs) used in volatile chemical products (VCPs). Both experimental and computational techniques are applied to analyze the photochemistry of the compound. We identify oxidation products from both bimolecular and autoxidation reactions from chamber experiments at varied HO2 levels and provide estimations of rate coefficients and product branching ratios for key reaction pathways. The H-shift processes of 2-EE peroxy radicals (RO2) are found to be sufficiently fast to compete with bimolecular reactions under modest NO/HO2 conditions. More than 30% of the produced RO2 are expected to undergo at least one H-shift for conditions typical of modern summer urban atmosphere, where RO2 bimolecular lifetime is becoming >10 s, which implies the potential for glycol ether oxidation to produce considerable amounts of HOMs at reduced NOx levels and elevated temperature. Understanding the gas-phase autoxidation of glycol ethers can help fill the knowledge gap in the formation of SOA derived from oxygenated VOCs emitted from VCP sources.

Elucidating climatic drivers of photosynthesis by tropical forests.

Tropical forests play a pivotal role in regulating the global carbon cycle. However, the response of these forests to changes in absorbed solar energy and water supply under the changing climate is highly uncertain. Three-year (2018-2021) spaceborne high-resolution measurements of solar-induced chlorophyll fluorescence (SIF) from the TROPOspheric Monitoring Instrument (TROPOMI) provide a new opportunity to study the response of gross primary production (GPP) and more broadly tropical forest carbon dynamics to differences in climate. SIF has been shown to be a good proxy for GPP on monthly and regional scales. Combining tropical climate reanalysis records and other contemporary satellite products, we find that on the seasonal timescale, the dependence of GPP on climate variables is highly heterogeneous. Following the principal component analyses and correlation comparisons, two regimes are identified: water limited and energy limited. GPP variations over tropical Africa are more correlated with water-related factors such as vapor pressure deficit (VPD) and soil moisture, while in tropical Southeast Asia, GPP is more correlated with energy-related factors such as photosynthetically active radiation (PAR) and surface temperature. Amazonia is itself heterogeneous: with an energy-limited regime in the north and water-limited regime in the south. The correlations of GPP with climate variables are supported by other observation-based products, such as Orbiting Carbon Observatory-2 (OCO2) SIF and FluxSat GPP. In each tropical continent, the coupling between SIF and VPD increases with the mean VPD. Even on the interannual timescale, the correlation of GPP with VPD is still discernable, but the sensitivity is smaller than the intra-annual correlation. By and large, the dynamic global vegetation models in the TRENDY v8 project do not capture the high GPP seasonal sensitivity to VPD in dry tropics. The complex interactions between carbon and water cycles in the tropics illustrated in this study and the poor representation of this coupling in the current suite of vegetation models suggest that projections of future changes in carbon dynamics based on these models may not be robust.

Limb and cardiovascular event risk in type 1 and 2 diabetic patients with peripheral artery disease.

Background: Peripheral artery disease (PAD) is a risk factor for adverse limb events (LE) and cardiovascular events (CVE) that coexists with type 1 (T1) and 2 (T2) diabetes mellitus (DM). Little is known about comparative risk of LE and CVE in T1/T2 DM patients with PAD. Patients and methods: We queried our database of 40,144 patients ≥18 years old who underwent ankle brachial index (ABI) measurement from 01/1996-02/2020. We isolated T1/T2 DM patients with PAD diagnosed by ankle brachial index (ABI; low [<1.0] or elevated [>1.4]) and retrieved demographics including glycated hemoglobin (HbA1c). Primary outcomes were LE (critical limb ischemia/vascular amputation) and CVE (myocardial infarction/ischemic stroke). All-cause mortality was a secondary outcome. Multivariable Cox proportional regression yielded hazard ratios (HR) with 95% confidence intervals (CI) after adjusting for pertinent risk factors including age, hypertension, hyperlipidemia, smoking, and HbA1c. Results: Our study found 10,156 patients with PAD and DM (34% T1DM, 66% T2DM) with median follow-up time 34 mo (IQR 85 mo). T1DM patients were younger than T2DM (mean age 67 vs. 70 years), with higher median HbA1c (7.7 [IQR 1.9] vs. 6.7% [IQR 1.6]), and more prevalent hypertension, hyperlipidemia, CAD, and CKD. Antiplatelet and statin use was equivocal. Elevated ABI was more common in T1DM (47 vs. 28%). LE occurred in 23% and CVE in 12% patients. LE risk was higher in T1 than T2 DM patients (HR 1.58 [95% CI 1.44, 1.73], p<0.0001), but CVE and all-cause mortality were equivocal. These observations were preserved across ABI and HbA1c subgroup analyses. Conclusions: PAD patients with T1DM had a higher LE risk than those with T2DM, even after adjustment for glycemic control and pertinent risk factors, but CVE risk and all-cause mortality were equivocal. These data suggest a potential role for more intensive LE risk modification in PAD patients with T1DM, but further investigation is needed.

Unequal exposure to heatwaves in Los Angeles: Impact of uneven green spaces.

Cities worldwide are experiencing record-breaking summer temperatures. Urban environments exacerbate extreme heat, resulting in not only the urban heat island but also intracity variations in heat exposure. Understanding these disparities is crucial to support equitable climate mitigation and adaptation efforts. We found persistent negative correlations between daytime land surface temperature (LST) and median household income across the Los Angeles metropolitan area based on Ecosystem Spaceborne Thermal Radiometer Experiment on Space Station observations from 2018 to 2021. Lower evapotranspiration resulting from the unequal distribution of vegetation cover is a major factor leading to higher LST in low-income neighborhoods. Disparities worsen with higher regional mean surface temperature, with a $10,000 decrease in income leading to ~0.2°C LST increase at 20°C and up to ~0.7°C at 45°C. With more frequent and intense heat waves projected in the future, equitable mitigation measures, such as increasing surface albedo and tree cover in low-income neighborhoods, are necessary to address these disparities.

Peripheral artery disease and the risk of venous thromboembolism.

Background: Peripheral artery disease (PAD) impacts 3-12% of patients worldwide and is characterized by endothelial dysfunction and inflammatory pathways which are also common to venous thromboembolism (VTE), but there is a paucity of evidence regarding VTE risk in PAD patients. We investigated whether PAD is an independent risk factor for VTE. Patients and methods: We reviewed medical records of patients undergoing ABI studies at Mayo Clinic from 01/1996-02/2020. We classified patients by ABI (low [<1.0], normal [1.0-1.4], or elevated [>1.4]), as well as by specific low ABI subgroup: severely reduced (ABI: 0.00-0.39), moderately reduced (0.40-0.69), mildly reduced (0.70-0.90), and borderline reduced (0.91-0.99). The primary outcome was incident VTE event (acute lower extremity deep vein thrombosis or pulmonary embolism) after ABI measurement. Multivariable Cox proportional regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) after adjusting for age, sex, active smoking, cancer, previous VTE, thrombophilia, anticoagulation, and revascularization. Results: 39,834 unique patients (mean age 66.3±14.3 years, median follow-up 34 months) were identified. 2,305 VTE events occurred in patients without PAD (13.0%), 2,218 in low ABI patients (13.0%), and 751 in elevated ABI patients (14.8%). After risk factor adjustment, VTE risk was modestly increased for PAD overall (HR: 1.12, 95% CI [1.06, 1.18]), including low ABI (HR: 1.11, 95% CI [1.04, 1.18]) and elevated ABI groups (HR: 1.15, 95% CI [1.04, 1.26]), compared to patients without PAD. The greatest VTE risk was in severely low ABI patients (HR: 1.46, 95% CI [1.31, 1.64]). Conclusions: In a large longitudinal cohort, we present strong clinical evidence of PAD, with low and elevated ABI, as an independent VTE risk factor, with the highest risk seen in patients with severely low ABI. Continued research is required to further investigate this relationship and its intersection with functional performance status to optimize VTE risk reduction or anticoagulation strategies in the PAD population.

Hydrocarbon Tracers Suggest Methane Emissions from Fossil Sources Occur Predominately Before Gas Processing and That Petroleum Plays Are a Significant Source.

We use global airborne observations of propane (C3H8) and ethane (C2H6) from the Atmospheric Tomography (ATom) and HIAPER Pole-to-Pole Observations (HIPPO), as well as U.S.-based aircraft and tower observations by NOAA and from the NCAR FRAPPE campaign as tracers for emissions from oil and gas operations. To simulate global mole fraction fields for these gases, we update the default emissions' configuration of C3H8 used by the global chemical transport model, GEOS-Chem v13.0.0, using a scaled C2H6 spatial proxy. With the updated emissions, simulations of both C3H8 and C2H6 using GEOS-Chem are in reasonable agreement with ATom and HIPPO observations, though the updated emission fields underestimate C3H8 accumulation in the arctic wintertime, pointing to additional sources of this gas in the high latitudes (e.g., Europe). Using a Bayesian hierarchical model, we estimate global emissions of C2H6 and C3H8 from fossil fuel production in 2016-2018 to be 13.3 ± 0.7 (95% CI) and 14.7 ± 0.8 (95% CI) Tg/year, respectively. We calculate bottom-up hydrocarbon emission ratios using basin composition measurements weighted by gas production and find their magnitude is higher than expected and is similar to ratios informed by our revised alkane emissions. This suggests that emissions are dominated by pre-processing activities in oil-producing basins.

Patient Age at Diagnosis of Peripheral Artery Disease and Its Impact on Cardiovascular and Limb Outcomes.

Peripheral artery disease (PAD) prevalence increases with age, but the relation between age at PAD diagnosis and outcomes is unclear. We investigated the cardiovascular and limb outcomes of patients diagnosed with PAD at different ages. We studied patients with PAD aged ≥18 years who were diagnosed between 1996 and 2020 at Mayo Clinic. Patients were grouped by diagnosis age (<50, 50 to 59, 60 to 69, ≥70 years) and ankle brachial index (ABI): low ABI (<1.0) or elevated ABI (>1.4). Primary outcomes were cardiovascular events (CVEs; myocardial infarction or ischemic stroke) and limb events (LEs; critical limb ischemia or amputation). Competing risk analysis was performed to calculate adjusted hazard ratios. The cohort included 22,073 patients with PAD (low ABI: 77.1%; elevated ABI: 22.9%). CVEs were observed in 8.2% of patients and LEs in 15.6%. The highest CVE risk was observed in patients diagnosed with PAD before age 50 (compared with patients diagnosed after age 70; hazard ratio 2.33 [95% confidence interval 1.95 to 2.78]). CVE risk decreased with older age at diagnosis. Although younger groups demonstrated higher LE risk, there was no clear association with diagnosis age. These patterns of risk were seen both in low and elevated ABI subgroups but in greater magnitude with elevated ABI. Younger patients diagnosed with PAD face increased risk of myocardial infarction and ischemic stroke compared with patients diagnosed at an older age. CVE risk notably exceeds LE risk. In conclusion, younger age at PAD diagnosis may be an important risk factor, which warrants more aggressive interventions focused on CVE prevention.

Hydrotrioxide (ROOOH) formation in the atmosphere.

Organic hydrotrioxides (ROOOH) are known to be strong oxidants used in organic synthesis. Previously, it has been speculated that they are formed in the atmosphere through the gas-phase reaction of organic peroxy radicals (RO2) with hydroxyl radicals (OH). Here, we report direct observation of ROOOH formation from several atmospherically relevant RO2 radicals. Kinetic analysis confirmed rapid RO2 + OH reactions forming ROOOH, with rate coefficients close to the collision limit. For the OH-initiated degradation of isoprene, global modeling predicts molar hydrotrioxide formation yields of up to 1%, which represents an annual ROOOH formation of about 10 million metric tons. The atmospheric lifetime of ROOOH is estimated to be minutes to hours. Hydrotrioxides represent a previously omitted substance class in the atmosphere, the impact of which needs to be examined.

Artificial intelligence for the evaluation of peripheral artery disease using arterial Doppler waveforms to predict abnormal ankle-brachial index.

BACKGROUND: Patients with peripheral artery disease (PAD) are at increased risk for major adverse limb and cardiac events including mortality. Developing screening tools capable of accurate PAD identification is a necessary first step for strategies of adverse outcome prevention. This study aimed to determine whether machine analysis of a resting Doppler waveform using deep neural networks can accurately identify patients with PAD. METHODS: Consecutive patients (4/8/2015 - 12/31/2020) undergoing rest and postexercise ankle-brachial index (ABI) testing were included. Patients were randomly allocated to training, validation, and testing subsets (70%/15%/15%). Deep neural networks were trained on resting posterior tibial arterial Doppler waveforms to predict normal (> 0.9) or PAD (⩽ 0.9) using rest and postexercise ABI. A separate dataset of 151 patients who underwent testing during a period after the model had been created and validated (1/1/2021 - 3/31/2021) was used for secondary validation. Area under the receiver operating characteristic curves (AUC) were constructed to evaluate test performance. RESULTS: Among 11,748 total patients, 3432 patients met study criteria: 1941 with PAD (mean age 69 ± 12 years) and 1491 without PAD (64 ± 14 years). The predictive model with highest performance identified PAD with an AUC 0.94 (CI = 0.92-0.96), sensitivity 0.83, specificity 0.88, accuracy 0.85, and positive predictive value (PPV) 0.90. Results were similar for the validation dataset: AUC 0.94 (CI = 0.91-0.98), sensitivity 0.91, specificity 0.85, accuracy 0.89, and PPV 0.89 (postexercise ABI comparison). CONCLUSION: An artificial intelligence-enabled analysis of a resting Doppler arterial waveform permits identification of PAD at a clinically relevant performance level.

The Post-thrombotic Syndrome-Prevention and Treatment: VAS-European Independent Foundation in Angiology/Vascular Medicine Position Paper.

Importance: The post-thrombotic syndrome (PTS) is the most common long-term complication of deep vein thrombosis (DVT), occurring in up to 40-50% of cases. There are limited evidence-based approaches for PTS clinical management. Objective: To provide an expert consensus for PTS diagnosis, prevention, and treatment. Evidence-Review: MEDLINE, Cochrane Database review, and GOOGLE SCHOLAR were searched with the terms "post-thrombotic syndrome" and "post-phlebitic syndrome" used in titles and abstracts up to September 2020. Filters Were: English, Controlled Clinical Trial / Systematic Review / Meta-Analysis / Guideline. The relevant literature regarding PTS diagnosis, prevention and treatment was reviewed and summarized by the evidence synthesis team. On the basis of this review, a panel of 15 practicing angiology/vascular medicine specialists assessed the appropriateness of several items regarding PTS management on a Likert-9 point scale, according to the RAND/UCLA method, with a two-round modified Delphi method. Findings: The panelists rated the following as appropriate for diagnosis: 1-the Villalta scale; 2- pre-existing venous insufficiency evaluation; 3-assessment 3-6 months after diagnosis of iliofemoral or femoro-popliteal DVT, and afterwards periodically, according to a personalized schedule depending on the presence or absence of clinically relevant PTS. The items rated as appropriate for symptom relief and prevention were: 1- graduated compression stockings (GCS) or elastic bandages for symptomatic relief in acute DVT, either iliofemoral, popliteal or calf; 2-thigh-length GCS (30-40 mmHg at the ankle) after ilio-femoral DVT; 3- knee-length GCS (30-40 mmHg at the ankle) after popliteal DVT; 4-GCS for different length of times according to the severity of periodically assessed PTS; 5-catheter-directed thrombolysis, with or without mechanical thrombectomy, in patients with iliofemoral obstruction, severe symptoms, and low risk of bleeding. The items rated as appropriate for treatment were: 1- thigh-length GCS (30-40 mmHg at the ankle) after iliofemoral DVT; 2-compression therapy for ulcer treatment; 3- exercise training. The role of endovascular treatment (angioplasty and/or stenting) was rated as uncertain, but it could be considered for severe PTS only in case of stenosis or occlusion above the inguinal ligament, followed by oral anticoagulation. Conclusions and Relevance: This position paper can help practicing clinicians in PTS management.

Ozone chemistry in western U.S. wildfire plumes.

Wildfires are a substantial but poorly quantified source of tropospheric ozone (O3). Here, to investigate the highly variable O3 chemistry in wildfire plumes, we exploit the in situ chemical characterization of western wildfires during the FIREX-AQ flight campaign and show that O3 production can be predicted as a function of experimentally constrained OH exposure, volatile organic compound (VOC) reactivity, and the fate of peroxy radicals. The O3 chemistry exhibits rapid transition in chemical regimes. Within a few daylight hours, the O3 formation substantially slows and is largely limited by the abundance of nitrogen oxides (NOx). This finding supports previous observations that O3 formation is enhanced when VOC-rich wildfire smoke mixes into NOx-rich urban plumes, thereby deteriorating urban air quality. Last, we relate O3 chemistry to the underlying fire characteristics, enabling a more accurate representation of wildfire chemistry in atmospheric models that are used to study air quality and predict climate.