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Atherosclerosis of the aorta is associated with increased risk of cardiovascular mortality and vascular events. We aim to describe the prevalence and distribution of non-calcified atherosclerotic plaque in the descending aorta as quantified by noncontrast cardiovascular magnetic resonance (CMR) in a community-dwelling cohort of adults.We used CMR to quantify noncalcified aortic plaque in 1726 participants (aged 65 ± 9 years, 46.7% men) from the Cohort Study Offspring cohort. ECG-gated, fat-suppressed, T2-weighted, black blood turbo spin echo sequence was used to acquire 36 transverse slices covering the descending aorta from just below the arch to the aortoiliac bifurcation. Plaque was defined as discrete luminal protrusions ≥1 mm; these were manually traced, then summed to determine total descending aortic plaque (DAP) and segmental thoracic and abdominal aortic plaque (TAP, AAP). Participants were stratified by sex and age group (55, 55-64, 65-74, ≥75y). A healthy referent group (without clinical cardiovascular disease, smoking, diabetes, impaired renal function; (N = 768, 43.8% men) was used to determine upper 90th percentile cutpoints for DAP and AAP which were then applied to the overall study cohort.Prevalence of DAP was similar between men (47.3%) and women (48.9%), p = 0.50, as was AAP prevalence (men: 44.5%, women: 46.7%, p = 0.16); TAP was less prevalent in both sexes (men: 8.9%, women: 7.1%, p = 0.15). Both prevalence and burden of DAP, AAP and TAP increased with advancing age.Noncalcified plaque prevalence, visualized on CMR, in community-dwelling adults is similar between the sexes, and both prevalence and burden of aortic plaque increase with greater age.

The association of mitral regurgitation (MR) severity and mortality in heart failure with preserved ejection fraction (HFpEF) is uncertain. We sought to evaluate the relation between MR severity on transthoracic echocardiography (TTE) and subsequent all-cause mortality in Medicare beneficiaries with HFpEF. We linked 57,608 patients referred for TTE at Beth Israel Deaconess Medical Center to Medicare inpatient claims from 2003 to 2017. In those with a history of HF and a physician-reported left ventricular ejection fraction ≥50%, we evaluated the relation of MR severity and time to the primary end point of all-cause mortality using Kaplan-Meier methods. A total of 7,778 individuals (14.5%) met inclusion criteria (mean age 75.5 years ± 11.9, 55.9% female). Over a median follow-up of 8.1 years, 2,016 (25.9%) died at a median (interquartile range) of 1.7 (0.3 to 4.1) years. At 1 year, 15.8% with 3 to 4+ MR had died versus 10.5% with 0 to 2+ MR (hazard ratio 1.54, 95% confidence interval 1.22 to 1.95, p0.001). After multivariable adjustment, 3 to 4+ MR continued to be associated with increased all-cause mortality (hazard ratio 1.48, 95% confidence interval 1.14 to 1.94, p = 0.004) except in the subset with atrial fibrillation (interaction p = 0.03) or recent (3 months) HF hospitalization (p = 0.54). In conclusion, in this large, single-institution retrospective study of Medicare beneficiaries with HFpEF who underwent TTE, moderate-to-severe and severe MR were significantly associated with an increased risk of all-cause mortality after multivariable adjustment, except in those with atrial fibrillation or recent HF. Prospective studies are needed to assess the role of MR reduction in mitigating this risk.

ObjectiveMajor depression in older adults increases the statistical likelihood of dementia. It is challenging to translate statistical evidence of cognitive decline at the group level into knowledge of individual cognitive outcomes. The objective of the current study is to investigate 2-year reliable cognitive change in late-life depression (LLD), which will enhance understanding of cognitive changes in LLD and provide a means to assess individual change.MethodsIn a sample of non-depressed cognitively normal older adults or NDCN (n = 113), we used linear regression to predict tests of global cognition, processing speed-executive functioning, and memory administered 1 and 2 years later. Stepwise regression was used to select covariates among demographics and raw test scores (either baseline or year 1) and we cross-validated the final models using the predicted residual error sum of squares (PRESS). We then derived a z-change score from the difference between actual and predicted follow-up scores and investigated the proportion of LLD patients (n = 199) and NDCN adults who experienced reliable “decline” (a z-score +1.645).ResultsA greater proportion LLD compared with NDCN experienced cognitive decline in processing speed/executive functioning and global cognition over 2 years. When compared to NDCN, a greater proportion of LLD also significantly improved on one test of processing speed over 2 years.ConclusionsOlder adults with LLD are at risk of meaningful cognitive decline over a relatively short period, particularly in the domain of executive functioning and processing speed. This study provides a series of reliable change equations for common neuropsychological tests that can be applied clinically.

Production and consumption of CFC-11 (trichlorofluoromethane, CCl3F), CFC-12 (dichlorodifluoromethane, CCl2F2) and CCl4 (carbon tetrachloride) are controlled under the regulations of the Montreal Protocol and have been phased out globally since 2010. Only CCl4 is still widely produced as a chemical feedstock. After 2010, emissions of CFC-11 and CFC-12 should therefore mostly originate from existing banks (e.g. from foams, mobile air conditioning units and refrigerators); however evidence has emerged of an increase in global emissions of CFC-11 in the last decade, some of which has not been fully accounted for. The motivation for this work was to assess the emissions of CFC-11, CFC-12 and CCl4 from western Europe. All countries in this region have been subject to the controls of the Montreal Protocol since the late 1980s and, as non-Article 5 Parties, have been prohibited from producing CFCs and CCl4 for dispersive use since 1996. Four different inverse modelling systems are used to estimate emissions of these gases from 2008 to 2021 using data from four atmospheric measurement stations: Mace Head (Ireland), Jungfraujoch (Switzerland), Monte Cimone (Italy) and Tacolneston (UK). The average of the four model studies found that western European emissions of CFC-11, CFC-12 and CCl4 between 2008 and 2021 were declining at 3.5 % yr−1 (2.7 % yr−1–4.8 % yr−1), 7.7 % yr−1 (6.3 % yr−1–8.0 % yr−1) and 4.4 % yr−1 (2.6 % yr−1–6.4 % yr−1), respectively. Even though the emissions were declining throughout the period, the area including northern France, Belgium, the Netherlands and Luxembourg showed consistently elevated emissions of CFC-11 compared with the surrounding regions. Emissions of CFC-12 were slightly elevated in the same region. CCl4 emissions were the highest in the south of France. France had the highest emissions of all three gases over the period 2008–2021. Emissions from western Europe (2008–2021) were on average 2.4 ± 0.4 Gg (CFC-11), 1.3 ± 0.3 Gg (CFC-12) and 0.9 ± 0.2 Gg (CCl4). Our estimated decline in emissions of CFC-11 is consistent with a western European bank release rate of 3.4 % (2.6 %–4.5 %). This study concludes that emissions of CFC-11, CFC-12 and CCl4 have all declined from 2008 to 2021 in western Europe. Therefore, no evidence is found that western European emissions contributed to the unexplained part of the global increase in atmospheric concentrations of CFC-11 observed in the last decade.

Global emissions of the ozone depleting gas 1,1-dichloro-1-fluoroethane (HCFC-141b, CH3CCl2F), derived from measurements of atmospheric mole fractions, have been rising between 2017–2021 despite a fall in reported production and consumption for dispersive uses. This study evaluates the possible drivers behind this renewed rise in emissions. HCFC-141b is a controlled substance under the Montreal Protocol, and its phase-out is currently underway, after a peak in reported consumption and production in developing countries (Article 5) in 2013. If reported production and consumption are correct, it suggests that the 2017–2021 rise is due to an increase in emissions from the bank when HCFC-141b containing appliances reach the end of their life, or from production of HCFC-141b not reported for dispersive uses. Regional emissions have been estimated between 2017–2020 for all regions where measurements have sufficient sensitivity to emissions. This includes the regions of northwestern Europe, east Asia, the USA and Australia, where emissions decreased by a total of 1.6 ± 3.9 Gg yr−1, compared to a mean global increase of 3.0 ± 1.2 Gg yr−1 over the same period. Collectively these regions only account for around a third of global emissions in 2020. Therefore we are not able to pinpoint the source regions or specific activities responsible for the recent global emission rise.

Patients with interatrial shunts (patient foramen ovale/atrial septal defect) are potentially at increased risk for paradoxical air embolism following computed tomography (CT) scans with intravenous (IV) contrast media injection. IV in-line filters aim to prevent such embolisms but are not compatible with power injection required for diagnostic CT.The purpose of this study was to determine whether the incidence of paradoxical embolism to the heart and brain in patients with an interatrial shunt is higher compared with controls within 48 hours following injection of IV contrast media without IV in-line filter.This is a retrospective cohort study conducted at a large tertiary academic center, which included a total of 2929 consecutive patients who underwent 8983 CT scans with IV contrast media injection between July 1, 2000 and April 30, 2018. Diagnosis of an interatrial shunt was confirmed by transthoracic or transesophageal echocardiography. Incidence and risk of cardiac embolic events (new troponin elevation,0.1 ng/mL) and neurological embolic events (new diagnosis of stroke/transient ischemic attacks) were evaluated.Among the 2929 patients analyzed (mean±SD age, 61±14 y), 475/2929 (16.2%) patients had an interatrial shunt. After applying the exclusion criteria, new elevated troponin was found in 8/329 (2.4%; 95% confidence interval [CI]: 1.1-4.7) patients with an interatrial shunt compared with 25/1687 (1.5%; 95% CI: 0.9-2.2) patients without an interatrial shunt. New diagnosis of stroke occurred in 2/169 (1%; 95% CI: 0.3-4.2) of patients with an interatrial shunt compared with 7/870 (0.8%; 95% CI: 0.4-1.7) without interatrial shunt.Among patients with echocardiographic evidence of an interatrial shunt, IV CT contrast administration without an in-line filter does not increase the incidence of cardiac or neurological events.

Biophysical cohesion, introduced predominantly by Extracellular Polymeric Substances (EPS) during mineral flocculation in subaqueous environments, plays important role in morphodynamics, biogeochemical cycles and ecosystem processes. However, the mechanism of how EPS functioning with cohesive particles and affects settling behaviors remain poorly understood. We measure initial flocculation rate, floc size and settling velocity of mineral and artificial EPS (Xanthan gum) mixtures. Combining results from these and previous studies demonstrate coherent intensification of EPS-related flocculation compare with those of pure mineral and oil-mineral mixtures. Importantly, the presence of EPS fundamentally changes floc structure and reduces variability of settling velocity. Measured data shows that ratios of microfloc and macrofloc settling velocity for pure mineral flocs is 3.9 but greatly reduced to a lowest value of 1.6 due to biological EPS addition. The low variability of settling velocity due to EPS participation explains the seemingly inconsistent results previously observed between field and laboratory studies.

Radiocarbon (14C) is a powerful tracer of fossil emissions because fossil fuels are entirely depleted in 14C, but observations of 14CO2 and especially 14CH4 in urban regions are sparse. We present the first observations of 14C in both methane (CH4) and carbon dioxide (CO2) in an urban area (London) using a recently developed sampling system. We find that the fossil fraction of CH4 and the atmospheric concentration of fossil CO2 are consistently higher than simulated values using the atmospheric dispersion model NAME coupled with emission inventories. Observed net biospheric uptake in June-July is not well correlated with simulations using the SMURF model with NAME. The results show the partitioning of fossil and biospheric CO2 and CH4 in cities can be evaluated and improved with 14C observations when the nuclear power plants influence is negligible.

Objectives:The relationships among depression, personality factors, and cognitive decline in the elderly are complex. Depressed elders score higher in neuroticism than nondepressed older individuals. Presence of neuroticism worsens cognitive decline in depressed older adults. Yet little is known about changes in neuroticism among older adults being treated for depression and the impact of these changes on cognitive decline.Design:Longitudinal observational study.Setting:Academic Health Center.Participants:We examined 68 participants in the neurobiology of late-life depression (LLD) study to test the hypothesis that older depressed subjects with more improvement in neuroticism would experience less cognitive decline compared with those with less change in neuroticism.Measurements:We measured neuroticism using the NEO-Personality Inventory-Revised at baseline and 1 year. Study psychiatrists measured depression using the Montgomery–Åsberg depression rating scale (MADRS). Global cognitive performance was measured using the Consortium to Establish a Registry for Alzheimer’s disease (CERAD) battery at baseline and annually over 3 years. Regression models of 1-year change in neuroticism and 3-year change in CERAD included sex, age, race, education, and 1-year change in MADRS score as covariates.Results:We found that among older adults, 1-year change in neuroticism was inversely associated with 3-year change in CERAD total score.Conclusions:Our findings challenge the notion of longitudinal stability of measures of personality, especially among older depressed individuals. They highlight the importance of repeated personality assessment, especially of neuroticism, in the management of LLD. Future studies in larger samples followed for longer periods are needed to confirm our results and to extend them to examine both cognitive change and development of dementia.

Context Neonate management remains a key issue in extensive beef production systems where producers are faced with substantial environmental and management challenges that limit their ability to monitor and manage livestock in a timely manner. Parturition is a critical event and can affect the calf health and survival, particularly in the perinatal period (up to 48 h after birth). As such, monitoring parturition using precision livestock technologies may provide producers with additional tools to manage their cattle and mitigate the impacts of neonatal mortality in extensive beef systems. Aims The purpose of this study was to determine whether data from a global navigation satellite system (GNSS) collar could be used to detect parturition events in extensively grazed beef cattle. Methods Forty-eight Bos taurus cows (583.5 kg body weight ± 9.25 s.e.m.) were allocated to a 28 ha paddock between 8 January 2021 and 6 March 2021 during the calving season. Thirty of the animals were fitted with GNSS-equipped collars (Smart Paddock, Vic., Australia) that captured data at 10 min intervals. Parturition events were recorded daily by visual observation. Collected data were used to calculate key predictive features related to calving behaviour. Derived features were compared and assessed for changes in the period surrounding parturition. Key results Increases were observed in distance to nearest neighbour and to herd aggregate features, and decreases were observed in paddock utilisation and distance travelled features in the lead-up to calving (P

Cohesive sediment forms flocs of various sizes and structures in the natural turbulent environment. Understanding flocculation is critical in accurately predicting sediment transport and biogeochemical cycles. In addition to aggregation and breakup, turbulence also reshapes flocs toward more stable structures. An Eulerian–Lagrangian framework has been implemented to investigate the effect of turbulence on flocculation by capturing the time-evolution of individual flocs. We have identified two floc reshaping mechanisms, namely breakage-regrowth and restructuring by hydrodynamic drag. Surface erosion is found to be the primary breakup mechanism for strong flocs, while fragile flocs tend to split into fragments of similar sizes. Aggregation of flocs of sizes comparable to or greater than the Kolmogorov scale is modulated by turbulence with lower aggregation efficiency. Our findings highlight the limiting effects of turbulence on both floc size and structure.

An extensive field campaign, the Ems-Dollard Measurements (EDoM), was executed in the Ems Estuary, bordering the Netherlands and Germany, aimed at better understanding the mechanisms that drive the exchange of water and sediments between a relatively exposed outer estuary and a hyper-turbid tidal river. More specifically, the reasons for the large up-estuary sediment accumulation rates and the role of the tidal river on the turbidity in the outer estuary were insufficiently understood. The campaign was designed to unravel the hydrodynamic and sedimentary exchange mechanisms, comprising two hydrographic surveys during contrasting environmental conditions using eight concurrently operating ships and 10 moorings measuring for at least one spring–neap tidal cycle. All survey locations were equipped with sensors measuring flow velocity, salinity, and turbidity (and with stationary ship surveys taking water samples), while some of the survey ships also measured turbulence and sediment settling properties. These observations have provided important new insights into horizontal sediment fluxes and density-driven exchange flows, both laterally and longitudinally. An integral analysis of these observations suggests that large-scale residual transport is surprisingly similar during periods of high and low discharge, with higher river discharge resulting in both higher seaward-directed fluxes near the surface and landward-directed fluxes near the bed. Sediment exchange seems to be strongly influenced by a previously undocumented lateral circulation cell driving residual transport. Vertical density-driven flows in the outer estuary are influenced by variations in river discharge, with a near-bed landward flow being most pronounced in the days following a period with elevated river discharge. The study site is more turbid during winter conditions, when the estuarine turbidity maximum (ETM) is pushed seaward by river flow, resulting in a more pronounced impact of suspended sediments on hydrodynamics. All data collected during the EDoM campaign, but also standard monitoring data (waves, water levels, discharge, turbidity, and salinity) collected by Dutch and German authorities are made publicly available at 4TU Centre for Research Data (https://doi.org/10.4121/c.6056564.v3; van Maren et al., 2022).

Knowledge of the spatial distribution of the fluxes of greenhouse gases (GHGs) and their temporal variability as well as flux attribution to natural and anthropogenic processes is essential to monitoring the progress in mitigating anthropogenic emissions under the Paris Agreement and to inform its global stocktake. This study provides a consolidated synthesis of CH4 and N2O emissions using bottom-up (BU) and top-down (TD) approaches for the European Union and UK (EU27 + UK) and updates earlier syntheses (Petrescu et al., 2020, 2021). The work integrates updated emission inventory data, process-based model results, data-driven sector model results and inverse modeling estimates, and it extends the previous period of 1990–2017 to 2019. BU and TD products are compared with European national greenhouse gas inventories (NGHGIs) reported by parties under the United Nations Framework Convention on Climate Change (UNFCCC) in 2021. Uncertainties in NGHGIs, as reported to the UNFCCC by the EU and its member states, are also included in the synthesis. Variations in estimates produced with other methods, such as atmospheric inversion models (TD) or spatially disaggregated inventory datasets (BU), arise from diverse sources including within-model uncertainty related to parameterization as well as structural differences between models. By comparing NGHGIs with other approaches, the activities included are a key source of bias between estimates, e.g., anthropogenic and natural fluxes, which in atmospheric inversions are sensitive to the prior geospatial distribution of emissions. For CH4 emissions, over the updated 2015–2019 period, which covers a sufficiently robust number of overlapping estimates, and most importantly the NGHGIs, the anthropogenic BU approaches are directly comparable, accounting for mean emissions of 20.5 Tg CH4 yr−1 (EDGARv6.0, last year 2018) and 18.4 Tg CH4 yr−1 (GAINS, last year 2015), close to the NGHGI estimates of 17.5±2.1 Tg CH4 yr−1. TD inversion estimates give higher emission estimates, as they also detect natural emissions. Over the same period, high-resolution regional TD inversions report a mean emission of 34 Tg CH4 yr−1. Coarser-resolution global-scale TD inversions result in emission estimates of 23 and 24 Tg CH4 yr−1 inferred from GOSAT and surface (SURF) network atmospheric measurements, respectively. The magnitude of natural peatland and mineral soil emissions from the JSBACH–HIMMELI model, natural rivers, lake and reservoir emissions, geological sources, and biomass burning together could account for the gap between NGHGI and inversions and account for 8 Tg CH4 yr−1. For N2O emissions, over the 2015–2019 period, both BU products (EDGARv6.0 and GAINS) report a mean value of anthropogenic emissions of 0.9 Tg N2O yr−1, close to the NGHGI data (0.8±55 % Tg N2O yr−1). Over the same period, the mean of TD global and regional inversions was 1.4 Tg N2O yr−1 (excluding TOMCAT, which reported no data). The TD and BU comparison method defined in this study can be operationalized for future annual updates for the calculation of CH4 and N2O budgets at the national and EU27 + UK scales. Future comparability will be enhanced with further steps involving analysis at finer temporal resolutions and estimation of emissions over intra-annual timescales, which is of great importance for CH4 and N2O, and may help identify sector contributions to divergence between prior and posterior estimates at the annual and/or inter-annual scale. Even if currently comparison between CH4 and N2O inversion estimates and NGHGIs is highly uncertain because of the large spread in the inversion results, TD inversions inferred from atmospheric observations represent the most independent data against which inventory totals can be compared. With anticipated improvements in atmospheric modeling and observations, as well as modeling of natural fluxes, TD inversions may arguably emerge as the most powerful tool for verifying emission inventories for CH4, N2O and other GHGs. The referenced datasets related to figures are visualized at https://doi.org/10.5281/zenodo.7553800 (Petrescu et al., 2023).

With the successful implementation of the Montreal Protocol on Substances that Deplete the Ozone Layer, the atmospheric abundance of ozone-depleting substances continues to decrease slowly and the Antarctic ozone hole is showing signs of recovery. However, growing emissions of unregulated short-lived anthropogenic chlorocarbons are offsetting some of these gains. Here, we report an increase in emissions from China of the industrially produced chlorocarbon, dichloromethane (CH2Cl2). The emissions grew from 231 (213–245) Gg yr−1 in 2011 to 628 (599–658) Gg yr−1 in 2019, with an average annual increase of 13 (12–15) %, primarily from eastern China. The overall increase in CH2Cl2 emissions from China has the same magnitude as the global emission rise of 354 (281−427) Gg yr−1 over the same period. If global CH2Cl2 emissions remain at 2019 levels, they could lead to a delay in Antarctic ozone recovery of around 5 years compared to a scenario with no CH2Cl2 emissions., Dichloromethane (CH2Cl2) is an unregulated ozone depleting substance whose emissions have strongly increased in recent years. Here, the authors show that rising emissions of dichloromethane in China between 2011 and 2019 can explain much of this global increase.

In 2021, there were 136 articles published in the Journal of Cardiovascular Magnetic Resonance (JCMR), including 122 original research papers, six reviews, four technical notes, one Society for Cardiovascular Magnetic Resonance (SCMR) guideline, one SCMR position paper, one study protocol, and one obituary (Nathaniel Reichek). The volume was up 53% from 2020 (n = 89) with a corresponding 21% decrease in manuscript submissions from 435 to 345. This led to an increase in the acceptance rate from 24 to 32%. The quality of the submissions continues to be high. The 2021 JCMR Impact Factor (which is released in June 2022) markedly increased from 5.41 to 6.90 placing us in the top quartile of Society and cardiac imaging journals. Our 5 year impact factor similarly increased from 6.52 to 7.25. Fifteen years ago, the JCMR was at the forefront of medical and medical society journal migration to the Open-Access format. The Open-Access system has dramatically increased the availability and JCMR citation. Full-text article requests in 2021 approached 1.5 M!. As I have mentioned, it takes a village to run a journal. JCMR is very fortunate to have a group of very dedicated Associate Editors, Guest Editors, Journal Club Editors, and Reviewers. I thank each of them for their efforts to ensure that the review process occurs in a timely and responsible manner. These efforts have allowed the JCMR to continue as the premier journal of our field. My role, and the entire editorial process would not be possible without the ongoing high dedication and efforts of our managing editor, Jennifer Rodriguez. Her premier organizational skills have allowed for streamlining of the review process and marked improvement in our time-to-decision (see later). As I conclude my 6th and final year as your editor-in-chief, I thank you for entrusting me with the JCMR editorship and appreciate the time I have had at the helm. I am very confident that our Journal will reach new heights under the stewardship of Dr. Tim Leiner, currently at the Mayo Clinic with a seamless transition occurring as I write this in late November. I hope that you will continue to send your very best, high quality CMR manuscripts to JCMR, and that our readers will continue to look to JCMR for the very best/state-of-the-art CMR publications.

Apathy is a common condition that involves diminished initiative, diminished interest and diminished emotional expression or responsiveness. It is highly prevalent in the context of a variety of neuropsychiatric disorders and is related to poor health outcomes. Presence of apathy is associated with cognitive and functional decline in dementia. Despite its negative impact on health, there is no definitive treatment for apathy, a clinical reality that may be due in part to lack of knowledge about assessment, neuropsychological features and neurobiological underpinnings. Here, we review and synthesize evidence from clinical, epidemiological, neuropsychological, peripheral biomarker and neuroimaging research. Apathy is a common feature of depression and cognitive disorders and is associated with impairment in executive function. Neuropsychological and neuroimaging studies point to dysfunction of brain circuitry involving the prefrontal cortex, especially the dorsolateral prefrontal cortex circuit, the dorsomedial prefrontal cortex circuit, and the ventromedial prefrontal cortex circuit. However, inconsistent findings, particularly in neuroimaging may be due to heterogeneity of apathy symptoms (with a need to better elucidate subtypes), neuropsychiatric comorbidities, the severity of cognitive impairment and other factors. These factors need to be accounted for in future studies so that biomarker research can make progress. On the whole, the literature on apathy has identified likely neurocognitive, peripheral biomarker and neuroimaging targets for understanding apathy, but also points to the need to address methodological issues that will better inform future studies. In turn, as we learn more about the underpinning of apathy and its subtypes, subsequent research can focus on new neurally based interventions that will strengthen the clinical management of apathy in the context of its comorbidities.

Background Stiffness of the proximal aorta may play a critical role in adverse left ventricular (LV)–vascular interactions and associated LV diastolic dysfunction. In a community‐based sample, we sought to determine the association between proximal aortic stiffness measured by cardiovascular magnetic resonance (CMR) and several clinical measures of LV diastolic mechanics. Methods and Results Framingham Heart Study Offspring adults (n=1502 participants, mean 67±9 years, 54% women) with available 1.5T CMR and transthoracic echocardiographic measures were included. Measures included proximal descending aortic strain and aortic arch pulse wave velocity by CMR (2002–2006) and diastolic function (mitral Doppler E and A wave velocity, E wave area, and LV tissue Doppler e' velocity) by echocardiography (2005–2008). Multivariable linear regression analysis was used to relate CMR aortic stiffness measures to measures of echocardiographic LV diastolic function. All continuous variables were standardized. In multivariable‐adjusted regression analyses, aortic strain was inversely associated with E wave deceleration time (estimated β=−0.10±0.032, P =0.001), whereas aortic arch pulse wave velocity was inversely associated with E/A ratio (estimated β=−0.094±0.027, P =0.0006), E wave area (estimated β=−0.070±0.027, P =0.010), and e' (estimated β=−0.061±0.027, P =0.022), all indicating associations of higher aortic stiffness by CMR with less favorable LV diastolic function. Compared with men, women had a larger inverse relationship between pulse wave velocity and E/A ratio (interaction β=−0.085±0.031, P =0.0064). There was no significant effect modification by age or a U‐shaped (quadratic) relation between aortic stiffness and LV diastolic function measures. Conclusions Higher proximal aortic stiffness is associated with less favorable LV diastolic function. Future studies may clarify temporal relations of aortic stiffness with varying patterns and progression of LV diastolic dysfunction.

Background In response to COVID-19 pandemic state restrictions, our institution deferred elective procedures from 3/15/2020 to 6/13/2020, and removed cardiology fellows from the echocardiography rotation to staff clinical services. We assessed the impact of the COVID-19 pandemic on fellow education and echocardiography volumes. Methods Our institutional database was used to examine volumes of transthoracic (TTE), stress (SE), and transesophageal echocardiograms (TEE) from 7/1/2018 to 10/10/2020. Study volumes were compared in three intervals: pre-pandemic (7/1/2018- 3/14/2020), pandemic (3/15/2020–6/13/2020), and pandemic recovery (6/14/2020–10/10/2020). We examined weekly number of TTEs performed or interpreted by cardiology fellows during the study period, and compared these to the two previous academic years. Results Weekly TTE volume declined by 54% during the pandemic, and increased by 99% during pandemic recovery, (p s=0.67, p p p Conclusion COVID restrictions between 3/15/2020- 6/14/2020 coincided with a marked decline in TTE, SE, and TEE volumes, with an increase similar to near pre-pandemic volumes during the pandemic recovery period. A similar decline with the onset of COVID restrictions, and increase to pre-restriction volumes thereafter was observed with fellow scans and interpretations, but total academic year fellow training volumes remained depressed. With the ongoing COVID-19 pandemic and rise of multiple variants, training programs may need to adjust fellows’ clinical responsibilities so as to support achievement of echocardiography training certification.

The optimal use of many biotherapeutics is restricted by Anti-drug antibodies (ADAs) and hypersensitivity responses which can affect potency and ability to administer a treatment. Here we demonstrate that Re-surfacing can be utilized as a generalizable approach to engineer proteins with extensive surface residue modifications in order to avoid binding by pre-existing ADAs. This technique was applied to E. coli Asparaginase (ASN) to produce functional mutants with up to 58 substitutions resulting in direct modification of 35% of surface residues. Re-surfaced ASNs exhibited significantly reduced binding to murine, rabbit and human polyclonal ADAs, with a negative correlation observed between binding and mutational distance from the native protein. Reductions in ADA binding correlated with diminished hypersensitivity responses in an in vivo mouse model. By using computational design approaches to traverse extended distances in mutational space while maintaining function, protein Re-surfacing may provide a means to generate novel or second line therapies for life-saving drugs with limited therapeutic alternatives.

In 2021, there were 136 articles published in the Journal of Cardiovascular Magnetic Resonance (JCMR), including 122 original research papers, six reviews, four technical notes, one Society for Cardiovascular Magnetic Resonance (SCMR) guideline, one SCMR position paper, one study protocol, and one obituary (Nathaniel Reichek). The volume was up 53% from 2020 (n = 89) with a corresponding 21% decrease in manuscript submissions from 435 to 345. This led to an increase in the acceptance rate from 24 to 32%. The quality of the submissions continues to be high. The 2021 JCMR Impact Factor (which is released in June 2022) markedly increased from 5.41 to 6.90 placing us in the top quartile of Society and cardiac imaging journals. Our 5 year impact factor similarly increased from 6.52 to 7.25. Fifteen years ago, the JCMR was at the forefront of medical and medical society journal migration to the Open-Access format. The Open-Access system has dramatically increased the availability and JCMR citation. Full-text article requests in 2021 approached 1.5 M!. As I have mentioned, it takes a village to run a journal. JCMR is very fortunate to have a group of very dedicated Associate Editors, Guest Editors, Journal Club Editors, and Reviewers. I thank each of them for their efforts to ensure that the review process occurs in a timely and responsible manner. These efforts have allowed the JCMR to continue as the premier journal of our field. My role, and the entire editorial process would not be possible without the ongoing high dedication and efforts of our managing editor, Jennifer Rodriguez. Her premier organizational skills have allowed for streamlining of the review process and marked improvement in our time-to-decision (see later). As I conclude my 6th and final year as your editor-in-chief, I thank you for entrusting me with the JCMR editorship and appreciate the time I have had at the helm. I am very confident that our Journal will reach new heights under the stewardship of Dr. Tim Leiner, currently at the Mayo Clinic with a seamless transition occurring as I write this in late November. I hope that you will continue to send your very best, high quality CMR manuscripts to JCMR, and that our readers will continue to look to JCMR for the very best/state-of-the-art CMR publications.

Aims Prediction of mitral (MR) and tricuspid (TR) regurgitation progression on transthoracic echocardiography (TTE) is needed to personalize valvular surveillance intervals and prognostication. Methods and results Structured TTE report data at Beth Israel Deaconess Medical Center, 26 January 2000–31 December 2017, were used to determine time to progression (≥1+ increase in severity). TTE predictors of progression were used to create a progression score, externally validated at Massachusetts General Hospital, 1 January 2002–31 December 2019. In the derivation sample (MR, N = 34 933; TR, N = 27 526), only 5379 (15.4%) individuals with MR and 3630 (13.2%) with TR had progression during a median interquartile range) 9.0 (4.1–13.4) years of follow-up. Despite wide inter-individual variability in progression rates, a score based solely on demographics and TTE variables identified individuals with a five- to six-fold higher rate of MR/TR progression over 10 years (high- vs. low-score tertile, rate of progression; MR 20.1% vs. 3.3%; TR 21.2% vs. 4.4%). Compared to those in the lowest score tertile, those in the highest tertile of progression had a four-fold increased risk of mortality. On external validation, the score demonstrated similar performance to other algorithms commonly in use. Conclusion Four-fifths of individuals had no progression of MR or TR over two decades. Despite wide interindividual variability in progression rates, a score, based solely on TTE parameters, identified individuals with a five- to six-fold higher rate of MR/TR progression. Compared to the lowest tertile, individuals in the highest score tertile had a four-fold increased risk of mortality. Prediction of long-term MR/TR progression is not only feasible but prognostically important.

Atmospheric measurements can be used as a tool to evaluate national greenhouse gas inventories through inverse modelling. Using 8 years of continuous methane (CH4) concentration data, this work assesses the United Kingdom's (UK) CH4 emissions over the period 2013–2020. Using two different inversion methods, we find mean emissions of 2.10 ± 0.09 and 2.12 ± 0.26 Tg yr−1 between 2013 and 2020, an overall trend of −0.05 ± 0.01 and −0.06 ± 0.04 Tg yr−2 and a 2 %–3 % decrease each year. This compares with the mean emissions of 2.23 Tg yr−1 and the trend of −0.03 Tg yr−2 (1 % annual decrease) reported in the UK's 2021 inventory between 2013 and 2019. We examine how sensitive these estimates are to various components of the inversion set-up, such as the measurement network configuration, the prior emissions estimate, the inversion method and the atmospheric transport model used. We find the decreasing trend to be due, primarily, to a reduction in emissions from England, which accounts for 70 % of the UK CH4 emissions. Comparisons during 2015 demonstrate consistency when different atmospheric transport models are used to map the relationship between sources and atmospheric observations at the aggregation level of the UK. The posterior annual national means and negative trend are found to be consistent across changes in network configuration. We show, using only two monitoring sites, that the same conclusions on mean UK emissions and negative trend would be reached as using the full six-site network, albeit with larger posterior uncertainties. However, emissions estimates from Scotland fail to converge on the same posterior under different inversion set-ups, highlighting a shortcoming of the current observation network in monitoring all of the UK. Although CH4 emissions in 2020 are estimated to have declined relative to previous years, this decrease is in line with the longer-term emissions trend and is not necessarily a response to national lockdowns.

ObjectiveTo identify potential race, sex and age disparities in performance of transthoracic echocardiography (TTE) over several decades.MethodsTTE reports from five academic and community sites within a single integrated healthcare system were linked to 100% Medicare fee-for-service claims from 1 January 2005 to 31 December 2017. Multivariable Poisson regression was used to estimate adjusted rates of TTE utilisation after the index TTE according to baseline age, sex, race and comorbidities among individuals with ≥2 TTEs. Non-white race was defined as black, Asian, North American Native, Hispanic or other categories using Medicare-assigned race categories.ResultsA total of 15 870 individuals (50.1% female, mean 72.2±12.7 years) underwent a total of 63 535 TTEs (range 2–55/person) over a median (IQR) follow-up time of 4.9 (2.4–8.5) years. After the index TTE, the median TTE use was 0.72 TTEs/person/year (IQR 0.43–1.33; range 0.12–26.76). TTE use was lower in older individuals (relative risk (RR) for 10-year increase in age, 0.91, 95% CI 0.89 to 0.92, pConclusionsAmong Medicare beneficiaries with multiple TTEs in a single large healthcare system, the median TTE use after the index TTE was 0.72 TTEs/person/year, although this varied widely. Adjusted for comorbidities, female sex, non-white race and advancing age were associated with decreased TTE utilisation.

Obesity is a risk factor for coronavirus disease 2019 (COVID-19) infection, with studies demonstrating the prevalence of individuals with obesity admitted with COVID-19 ranging between 30 and 60%. We determined whether early changes in microRNAs (miRNAs) are associated with dysregulation of angiotensin-converting enzyme 2 (ACE2), the specific functional receptor for severe acute respiratory syndrome coronavirus 2. ACE2 is a membrane-bound enzyme that catalyzes the conversion of angiotensin II to angiotensin 1-7 the latter having cardioprotective and vasorelaxation effects. Quantitative real-time PCR analysis of plasma samples for circulating miRNAs showed upregulation of miR-200c and miR-let-7b in otherwise healthy individuals with obesity. This was associated with significant downregulation of ACE2, a direct target for both miRNAs, in individuals with obesity. Correlation analysis confirmed a significant negative correlation between ACE2 and both the miRNAs. Studies showed that despite being the functional receptor, inhibition/downregulation of ACE2 did not reduce the severity of COVID-19 infection. In contrast, increased angiotensin II following inhibition of ACE2 may increase the severity of the disease. Taken together, our novel results identify that upregulation of miR-200c may increase the susceptibility of individuals with obesity to COVID-19. Considering miRNA are the earliest molecular regulators, the level of circulating miR-200c could be a potential biomarker in the early identification of those at the risk of severe COVID-19.

OBJECTIVE: Assess cognitive impairment (global cognition and executive functioning) in older incarcerated males overall, and according to education and race. DESIGN: Cross-sectional PARTICIPANTS: The sample included 239 racially diverse (37.7% White, 41.4% Black, 20.9% Hispanic/Other) incarcerated males age ≥50 (mean age = 56.4±6.1; range 50–79 years). MEASUREMENTS: Global cognitive impairment assessed using the Montreal Cognitive Assessment (MoCA) – standard MoCA scoring (1-point adjustment for ≤12 years education, and score

In recent decades, oil spill contamination has tended to occur more commonly in deltaic and estuarial systems. The management of oil spillages has been a major challenge in the surrounding deltas due to the highly sensitivity nature of deltaic ecosystems. Many deltas have an abundance of clay minerals that can flocculate, and these play an important role in determining the transport of spilled oil contamination and its eventual fate, particularly given that suspended sediment and microbial activities are often prevalent and diverse in natural environments. The primary work presented here focuses on laboratory experimental studies that help develop improved parameterizations of flocculation processes for oil-sediment-biogeochemical modeling. Oil-mineral flocs (OMA) have been successfully created from a series of laboratory flocculation experiments. A floc video instrument LabSFLOC-2 has been adopted for the first time to study the settling dynamics of OMAs. Experimental results reveal OMAs can easily form in any oil, cohesive sediment, and seawater mixtures. However, Kaolin and Bentonite forms dramatically different OMA structures, which leads to their variable characteristics. In the Bentonite clay cases, the oil flocs tend to be much larger and with higher densities than those in Kaolin clay cases, resulting in significant variability of flocs settling velocities.

Apathy is a common condition that involves diminished initiative, diminished interest and diminished emotional expression or responsiveness. It is highly prevalent in the context of a variety of neuropsychiatric disorders and is related to poor health outcomes. Presence of apathy is associated with cognitive and functional decline in dementia. Despite its negative impact on health, there is no definitive treatment for apathy, a clinical reality that may be due in part to lack of knowledge about assessment, neuropsychological features and neurobiological underpinnings. Here, we review and synthesize evidence from clinical, epidemiological, neuropsychological, peripheral biomarker and neuroimaging research. Apathy is a common feature of depression and cognitive disorders and is associated with impairment in executive function. Neuropsychological and neuroimaging studies point to dysfunction of brain circuitry involving the prefrontal cortex, especially the dorsolateral prefrontal cortex circuit, the dorsomedial prefrontal cortex circuit, and the ventromedial prefrontal cortex circuit. However, inconsistent findings, particularly in neuroimaging may be due to heterogeneity of apathy symptoms (with a need to better elucidate subtypes), neuropsychiatric comorbidities, the severity of cognitive impairment and other factors. These factors need to be accounted for in future studies so that biomarker research can make progress. On the whole, the literature on apathy has identified likely neurocognitive, peripheral biomarker and neuroimaging targets for understanding apathy, but also points to the need to address methodological issues that will better inform future studies. In turn, as we learn more about the underpinning of apathy and its subtypes, subsequent research can focus on new neurally based interventions that will strengthen the clinical management of apathy in the context of its comorbidities.

Arrestin or G protein bias may be desirable for novel cannabinoid therapeutics. Arrestin-2 and arrestin-3 translocation to CBSite-directed mutagenesis was conducted to generate nine different phosphorylation-impaired CBThe effects of each mutation were shared for arrestin-2 and arrestin-3 translocation to CBThese data do not support the existence of an 'essential' pxxp motif for arrestin translocation to CB

The relationships among depression, personality factors, stress, and cognitive decline in the elderly are complex. Depressed elders score higher in neuroticism than nondepressed older individuals. Independently, the presence of neuroticism and the number of stressful life events are each associated with worsening cognitive decline in depressed older adults. Yet little is known about combined effects of changes in neuroticism and changes in stress on cognitive decline among older depressed adults.Longitudinal observational study.Academic Health Center.The authors examined 62 participants in the Neurobiology of Late-life depression (NBOLD) study to test the hypothesis that, compared with older depressed subjects who experience improved neuroticism and lower psychosocial stressors over time, those with worsening neuroticism and greater psychosocial stressors will demonstrate more cognitive decline.The authors measured neuroticism using the NEO-Personality Inventory-Revised at baseline and 1 year. Study psychiatrists measured depression using the Montgomery-Ǻsberg Depression Rating Scale. At annual assessments, subjects reported the number of psychosocial stressors in the prior year and completed a neuropsychological evaluation. Participants completed a detailed neuropsychological battery at baseline and annually over 3 years. The battery included a test of delayed story memory (Logical Memory-2 or LMII). The outcome 3-year change in cognitive scores was regressed against 3-year change scores of neuroticism and number of psychosocial stressors, plus their interaction, while adjusting for sex, age, race, education, baseline cognitive score, and 3-year change in MADRS score as covariates.In multivariable linear regression analysis with the above covariates, the interaction effect of 3-year change in Total Neuroticism score and 3-year change in Total Stressors on change in LMII performance was statistically significant (B = -0.080[95%CL: -0.145 to -0.015], T = -2.48, df = 52, p = 0.017). Further exploration of this finding showed that 1) when total stressors increased by 2 or more over 3 years, LMII change was inversely associated with neuroticism change; and 2) when neuroticism improved less, LMII change score was inversely associated with total stressor change. There were no other significant interactions between stress and neuroticism on cognition.Our findings document the importance of tracking change in neuroticism and monitoring psychosocial stress over the long-term course of treatment in geriatric depression. Both factors exert important combined effects on memory over time. Future studies in larger samples are needed to confirm our results and to extend them to examine both cognitive change and development of dementia.

Knowledge of the spatial distribution of the fluxes of greenhouse gases and their temporal variability as well as flux attribution to natural and anthropogenic processes is essential to monitoring the progress in mitigating anthropogenic emissions under the Paris Agreement and to inform its Global Stocktake. This study provides a consolidated synthesis of CH4 and N2O emissions using bottom-up (BU) and top-down (TD) approaches for the European Union and UK (EU27+UK) and updates earlier syntheses (Petrescu et al., 2020, 2021). The work integrates updated emission inventory data, process-based model results, data-driven sector model results, inverse modelling estimates, and extends the previous period 1990–2017 to 2020. BU and TD products are compared with European National GHG Inventories (NGHGI) reported by Parties under the United Nations Framework Convention on Climate Change (UNFCCC) in 2021. The uncertainties of NGHGIs were evaluated using the standard deviation obtained by varying parameters of inventory calculations, reported by the EU Member States following the guidelines of the Intergovernmental Panel on Climate Change (IPCC) and harmonized by gap-filling procedures. Variation in estimates produced with other methods, such as atmospheric inversion models (TD) or spatially disaggregated inventory datasets (BU), arise from diverse sources including within-model uncertainty related to parameterization as well as structural differences between models. By comparing NGHGIs with other approaches, the activities included are a key source of bias between estimates e.g. anthropogenic and natural fluxes, which, in atmospheric inversions are sensitive to the prior geospatial distribution of emissions. For CH4 emissions, over the updated 2015–2019 period, which covers a sufficiently robust number of overlapping estimates, and most importantly the NGHGIs, the anthropogenic BU approaches are directly comparable, accounting for mean emissions of 20.5 Tg CH4 yr−1 (EDGAR v5v6.0, last year 2018) and 18.4 Tg CH4 yr−1 (GAINS, 2015), close to the NGHGI estimates of 17.5 ± 2.1 Tg CH4 yr−1. TD inversions estimates give higher emission estimates, as they also detect natural emissions. Over the same period, high resolution regional TD inversions report a mean emission of 34 Tg CH4 yr−1. Coarser-resolution global-scale TD inversions result in emission estimates of 23 Tg CH4 yr−1 and 24 Tg CH4 yr−1 inferred from GOSAT and surface (SURF) network atmospheric measurements, respectively. The magnitude of natural peatland and mineral soils emissions from the JSBACH-HIMMELI model, natural rivers, lakes and reservoirs emissions, geological sources and biomass burning together could account for the gap between NGHGI and inversions and account for 8 Tg CH4 yr−1. For N2O emissions, over the 2015–2019 period, both BU products (EDGAR v5v6.0 and GAINS) report a mean value of anthropogenic emissions of 0.9 Tg N2O yr−1, close to the NGHGI data (0.8 ± 55 % Tg N2O yr−1). Over the same period, the mean of TD global and regional inversions was 1.4 Tg N2O yr−1 (excluding TOMCAT which reported no data). The TD and BU comparison method defined in this study can be "operationalized" for future annual updates for the calculation of CH4 and N2O budgets at the national and EU27+UK scales. Future comparability will be enhanced with further steps involving analysis at finer temporal resolutions and estimation of emissions over intra-annual timescales, of great importance for CH4 and N2O, which may help identify sector contributions to divergence between prior and posterior estimates at the annual/inter-annual scale. Even if currently comparison between CH4 and N2O inversions estimates and NGHGIs is highly uncertain because of the large spread in the inversion results, TD inversions inferred from atmospheric observations represent the most independent data against which inventory totals can be compared. With anticipated improvements in atmospheric modelling and observations, as well as modelling of natural fluxes, TD inversions may arguably emerge as the most powerful tool for verifying emissions inventories for CH4, N2O and other GHGs. The referenced datasets related to figures are visualized at https://doi.org/10.5281/zenodo.6992472 (Petrescu et al., 2022).