Search

Summary: Background: People with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and without diabetes. Methods: The PHOSP-COVID study is a multicentre, long-term follow-up study of adults discharged from hospital between 1 February 2020 and 31 March 2021 in the UK following COVID-19, involving detailed assessment at 5 and 12 months after discharge. The association between diabetes status and outcomes were explored using multivariable linear and logistic regressions. Findings: People with diabetes who survived hospital admission with COVID-19 display worse physical outcomes compared to those without diabetes at 5- and 12-month follow-up. People with diabetes displayed higher fatigue (only at 5 months), frailty, lower physical performance, and health-related quality of life and poorer cognitive function. Differences in outcomes between diabetes status groups were largely consistent from 5 to 12-months. In regression models, differences at 5 and 12 months were attenuated after adjustment for BMI and presence of other long-term conditions. Interpretation: People with diabetes reported worse physical outcomes up to 12 months after hospital discharge with COVID-19 compared to those without diabetes. These data support the need to reduce inequalities in long-term physical and mental health effects of SARS-CoV-2 infection in people with diabetes. Funding: UK Research and Innovation and National Institute for Health Research. The study was approved by the Leeds West Research Ethics Committee (20/YH/0225) and is registered on the ISRCTN Registry (ISRCTN10980107).

Background: Most patients undergoing total knee arthroplasty (TKA) report moderate to severe pain in the acute postoperative period. Recent preliminary data have suggested that a short course of oral corticosteroid may improve early postoperative pain after various orthopedic operations, but the safety of this practice has not been rigorously evaluated in larger patient populations. The purpose of this study was to evaluate complication rates in patients receiving a methylprednisolone taper (MT) vs controls after primary TKA. Methods: Records were reviewed for patients undergoing primary TKA from 2018 to 2023 by 2 surgeons at different institutions who began routinely prescribing a 6-day MT to patients without a contraindication or poorly controlled diabetes. The primary outcome of periprosthetic joint infection at 90 days and final follow-up was assessed as were secondary outcomes of surgical site infection and wound complications. A total of 930 patients were included in the study, with 641 patients in the control cohort and 289 patients in the methylprednisolone cohort. Results: There were no significant differences between the methylprednisolone and control cohorts in 90-day periprosthetic joint infection (0.7% vs 0%, P = .1, respectively), surgical site infection (1.0% vs 1.4%, P = .4, respectively), or wound complication (1.0% vs 2.0%, P = .4, respectively). There were no significant differences in any complication at final follow-up. Conclusions: MT following TKA did not significantly increase rates of wound complications or infections in this multi-institutional retrospective cohort study. This study provides preliminary evidence regarding the safety profile of a short duration of postoperative oral corticosteroids following TKA.

Objective Liver disease is a growing cause of premature death in the UK. The National Health Service in England (NHS England) has funded regional early detection programmes through Community Liver Health Check pilots. ‘Alright My Liver?’ is Bristol and Severn’s pilot service offering early detection of liver disease through screening events serving populations at risk, including people with a history of drug or alcohol use, type 2 diabetes and obesity. The service offers point-of-care testing for liver disease and a supported follow-up process.Methods Semistructured interviews were conducted with 14 service users and six service providers over a 6-month period using diversity sampling. Topic guides encouraged discussion of experiences of the service as well as barriers and facilitators to accessing the service. Data were analysed using thematic analysis, and positive and negative comments pertaining to the service were collated in a ‘table of changes’ to inform optimisation.Results Three main themes were identified: (1) motivations for engagement, (2) experience of the service and (3) health impacts. Key motivations for engagement were screening as a novel opportunity, a response to immediate health concerns or as reassurance. Service users commented on its convenience and that staff interactions were warm and informative. Some felt that follow-up could be more intensive. Impacts varied depending on perceived risk factors and screening results but generally involved stating a commitment to healthy lifestyle changes, including reducing alcohol use.Conclusion Targeted screening for liver disease in high-risk groups through this pilot service was deemed an appropriate and accessible intervention, with important optimisations identified.

Innovative solutions are required to make long-duration space missions feasible. Crew performance and health is paramount to the success of anticipated Moon and Mars missions. Metabolic reduction via a quasi-torpor state is a possible mitigation strategy that can reduce consumable payload, which is necessary given the lack of available resupply options, and to reduce psychological stress, which is a risk for such lengthy missions. Even in lunar or cis-lunar missions, a quasi-torpor state could be implemented as an emergency countermeasure for critical situations where life support becomes limited. However, to date no studies have tested a quasi-torpor state in humans, and the impacts of intentional prolonged metabolic reduction on physiological and psychological parameters are unknown. To this end, we planned a three-phase study to provide proof-in-principle of the tolerability, feasibility, and side effects of a non-intravenous alpha-2-adrenergic receptor agonist for moderate sedation. This was accomplished by 1) determining the dosing and metabolic effects for different non-intravenous routes of alpha-2-adrenergic receptor agonist drugs; 2) assessing the degree of metabolic reduction and side effects during a 24-h quasi-torpor protocol; and 3) evaluating participant performance and total metabolic reduction achieved over a 5-day quasi-torpor protocol. We also aim to determine how skeletal muscle health and performance are affected by this quasi-torpor state. Quasi-torpor induced changes in skeletal muscle health and performance, as well as impacts on cognition and psychological stress, also have implications for terrestrial situations that result in prolonged confinement (e.g., austere environments such as submarine or remote scientific or military deployment and protracted critical illness). The findings of this three-phase study will be immediately applicable as a rescue strategy for emergencies during current or upcoming space missions. They will also identify key physiological and practical questions that need to be addressed for future deployment in long-duration space missions. This paper reviews the relevant literature that informed our rationale and approaches for this three-phase study.

Abstract Background Preoperative frailty is associated with increased risk of adverse outcomes. In 2017, McIsaac and colleagues’ systematic review found that few interventions improved outcomes in this population and evidence was low-quality. We aimed to systematically review the evidence for multicomponent perioperative interventions in frail patients that has emerged since McIsaac et al.’s review. Methods PUBMED, EMBASE, Cochrane, and CINAHL databases were searched for English-language studies published since January 1, 2016, that evaluated multicomponent perioperative interventions in patients identified as frail. Quality was assessed using the National Institute of Health Quality Assessment Tool. A narrative synthesis of the extracted data was conducted. Results Of 2835 articles screened, five studies were included, all of which were conducted in elective oncologic gastrointestinal surgical populations. Four hundred and thirteen patients were included across the five studies and the mean/median age ranged from 70.1 to 87.0 years. Multicomponent interventions were all applied in the preoperative period. Two studies also applied interventions postoperatively. All interventions addressed exercise and nutritional domains with variability in timing, delivery, and adherence. Multicomponent interventions were associated with reduced postoperative complications, functional deterioration, length of stay, and mortality. Four studies reported on patient-centred outcomes. The quality of evidence was fair. Conclusions This systematic review provides evidence that frail surgical patients undergoing elective oncologic gastrointestinal surgery may benefit from targeted multicomponent perioperative interventions. Yet methodological issues and substantial heterogeneity of the interventions precludes drawing clear conclusions regarding the optimal model of care. Larger, low risk of bias studies are needed to evaluate optimal intervention delivery, effectiveness in other populations, implementation in health care settings and ascertain outcomes of importance for frail patients and their carers.

Background The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p

Abstract Background Frailty is prevalent in older people with chronic kidney disease (CKD) and robust evidence supporting the benefit of dialysis in this setting is lacking. We aimed to measure frailty and quality of life (QOL) longitudinally in older people with advanced CKD and assess the impact of dialysis initiation on frailty, QOL and mortality. Methods Outpatients aged ≥65 with an eGFR ≤ 20ml/minute/1.73m2 were enrolled in a prospective observational study and followed up four years later. Frailty status was measured using a Frailty Index (FI), and QOL was evaluated using the EuroQol 5D-5L instrument. Mortality and dialysis status were determined through inspection of electronic records. Results Ninety-eight participants were enrolled. Between enrolment and follow-up, 36% of participants commenced dialysis and 59% died. Frailty prevalence increased from 47% at baseline to 86% at follow-up (change in median FI = 0.22, p

Abstract Fog holes were reported over cities of the Indo‐Gangetic plains of India, which were attributed to the urban heat island (UHI) effect. The present study reports the observational evidence of fog holes over rural area using satellite and ground observations. Delayed onset and early dissipation of fog is observed over the holes. Numerical simulations demonstrate that aerosol‐radiation interaction (ARI) leads to fog holes over both urban and rural regions. The anthropogenic aerosols and associated ARI dominate the UHI effect over the urban fog holes, while the aerosol absorption due to ARI mainly controls the rural fog holes. Turning off aerosol absorption causes ∼ 2 hours delay in the fog dissipation over urban area, whereas it yields persistent fog over rural area under saturated environment. An enhancement of soluble Aitken black carbon over the fog holes indicates the importance of aging process during fog dissipation.

Background Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known.Objectives To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors.Methods In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health.Results From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86).Conclusion Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need.Trail registration number ISRCTN10980107.

Aerosol radiative forcing uncertainty affects estimates of climate sensitivity and limits model skill in terms of making climate projections. Efforts to improve the representations of physical processes in climate models, including extensive comparisons with observations, have not significantly constrained the range of possible aerosol forcing values. A far stronger constraint, in particular for the lower (most-negative) bound, can be achieved using global mean energy balance arguments based on observed changes in historical temperature. Here, we show that structural deficiencies in a climate model, revealed as inconsistencies among observationally constrained cloud properties in the model, limit the effectiveness of observational constraint of the uncertain physical processes. We sample the uncertainty in 37 model parameters related to aerosols, clouds, and radiation in a perturbed parameter ensemble of the UK Earth System Model and evaluate 1 million model variants (different parameter settings from Gaussian process emulators) against satellite-derived observations over several cloudy regions. Our analysis of a very large set of model variants exposes model internal inconsistencies that would not be apparent in a small set of model simulations, of an order that may be evaluated during model-tuning efforts. Incorporating observations associated with these inconsistencies weakens any forcing constraint because they require a wider range of parameter values to accommodate conflicting information. We show that, by neglecting variables associated with these inconsistencies, it is possible to reduce the parametric uncertainty in global mean aerosol forcing by more than 50 %, constraining it to a range (around −1.3 to −0.1 W m−2) in close agreement with energy balance constraints. Our estimated aerosol forcing range is the maximum feasible constraint using our structurally imperfect model and the chosen observations. Structural model developments targeted at the identified inconsistencies would enable a larger set of observations to be used for constraint, which would then very likely narrow the uncertainty further and possibly alter the central estimate. Such an approach provides a rigorous pathway to improved model realism and reduced uncertainty that has so far not been achieved through the normal model development approach.

Abstract Aims The frailty index (FI) is one way in which frailty can be quantified. While it is measured as a continuous variable, various cut-off points have been used to categorise older adults as frail or non-frail, and these have largely been validated in the acute care or community settings for older adults without cancer. This review aimed to explore which FI categories have been applied to older adults with cancer and to determine why these categories were selected by study authors. Methods This scoping review searched Medline, EMBASE, Cochrane, CINAHL, and Web of Science databases for studies which measured and categorised an FI in adults with cancer. Of the 1994 screened, 41 were eligible for inclusion. Data including oncological setting, FI categories, and the references or rationale for categorisation were extracted and analysed. Results The FI score used to categorise participants as frail ranged from 0.06 to 0.35, with 0.35 being the most frequently used, followed by 0.25 and 0.20. The rationale for FI categories was provided in most studies but was not always relevant. Three of the included studies using an FI > 0.35 to define frailty were frequently referenced as the rationale for subsequent studies, however, the original rationale for this categorisation was unclear. Few studies sought to determine or validate optimum FI categorises in this population. Conclusion There is significant variability in how studies have categorised the FI in older adults with cancer. An FI ≥ 0.35 to categorise frailty was used most frequently, however an FI in this range has often represented at least moderate to severe frailty in other highly-cited studies. These findings contrast with a scoping review of highly-cited studies categorising FI in older adults without cancer, where an FI ≥ 0.25 was most common. Maintaining the FI as a continuous variable is likely to be beneficial until further validation studies determine optimum FI categories in this population. Differences in how the FI has been categorised, and indeed how older adults have been labelled as ‘frail’, limits our ability to synthesise results and to understand the impact of frailty in cancer care.

Global model studies and observations have shown that downward transport of aerosol nucleated in the free troposphere is a major source of cloud condensation nuclei (CCN) to the global boundary layer. In Amazonia, observations show that this downward transport can occur during strong convective activity. However, it is not clear from these studies over what spatial scale this cycle of aerosol formation and downward supply of CCN is occurring. Here, we aim to quantify the extent to which the supply of aerosol to the Amazonian boundary layer is generated from nucleation within a 1000 km regional domain or from aerosol produced further afield and the effectiveness of the transport by deep convection. We run the atmosphere-only configuration of the HadGEM3 climate model incorporating a 440 km × 1080 km regional domain over Amazonia with 4 km resolution. Simulations were performed over several diurnal cycles of convection. Below 2 km altitude in the regional domain, our results show that new particle formation within the regional domain accounts for only between 0.2 % and 3.4 % of all Aitken and accumulation mode aerosol particles, whereas nucleation that occurred outside the domain (in the global model) accounts for between 58 % and 81 %. The remaining aerosol is primary in origin. Above 10 km, the regional-domain nucleation accounts for up to 66 % of Aitken and accumulation mode aerosol, but over several days very few of these particles nucleated above 10 km in the regional domain are transported into the boundary layer within the 1000 km region, and in fact very little air is mixed that far down. Rather, particles transported downwards into the boundary layer originated from outside the regional domain and entered the domain at lower altitudes. Our model results show that CCN entering the Amazonian boundary layer are transported downwards gradually over multiple convective cycles on scales much larger than 1000 km. Therefore, on a 1000 km scale in the model (approximately one-third the size of Amazonia), trace gas emission, new particle formation, transport and CCN production do not form a “closed loop” regulated by the biosphere. Rather, on this scale, long-range transport of aerosol is a much more important factor controlling CCN in the boundary layer.

Background. Clinical Practice Guidelines suggest that frailty be measured during kidney transplant eligibility assessments. Yet it is not known how frailty is best assessed in this setting or whether its assessment is acceptable to patients. We aimed to examine the construct validity and feasibility of Frailty Index (FI) assessment among patients attending a kidney transplant assessment clinic and to explore patients’ perspectives on frailty and the acceptability of its routine assessment. Methods. A 58-item FI was calculated for 147 clinic patients. Semistructured interviews were conducted with a subgroup of 29 patients. The FI was validated against normative FI characteristics (mean, distribution, limit), age, and the Estimated Post-Transplant Survival Score. Feasibility was assessed using descriptive statistics. Qualitative data were analyzed using reflexive thematic analysis. Results. The mean FI was 0.23 (±0.10, normal distribution, limit 0.53). FI increased with age and Estimated Post-Transplant Survival score. The FI was completed for 62.8% of eligible patients (147/234). The median completion time was 10 min, and completion rate (with no missing data) was 100%. Four themes were identified: perceptions of frailty, acceptability, perceived benefits, and risks of frailty measurement. Patients linked frailty with age and adverse outcomes, and most did not consider themselves frail. Patients reported that the FI was quick, simple, and efficient. They felt that frailty assessment is relevant to transplant eligibility and should be used to address potentially reversible factors. Conclusions. The FI demonstrated construct validity and was feasible and acceptable in this clinic setting. The challenge is ensuring that routine assessments lead to better care.

Abstract Background There is currently no consensus as to a standardized tool for frailty measurement in any patient population. In the solid-organ transplantation population, routinely identifying and quantifying frailty in potential transplant candidates would support patients and the multidisciplinary team to make well-informed, individualized, management decisions. The aim of this scoping review was to synthesise the literature regarding frailty measurement in solid-organ transplant (SOT) candidates. Methods A search of four databases (Cochrane, Pubmed, EMBASE and CINAHL) yielded 3124 studies. 101 studies (including heart, kidney, liver, and lung transplant candidate populations) met the inclusion criteria. Results We found that studies used a wide range of frailty tools (N = 22), including four ‘established’ frailty tools. The most commonly used tools were the Fried Frailty Phenotype and the Liver Frailty Index. Frailty prevalence estimates for this middle-aged, predominantly male, population varied between 2.7% and 100%. In the SOT candidate population, frailty was found to be associated with a range of adverse outcomes, with most evidence for increased mortality (including post-transplant and wait-list mortality), post-operative complications and prolonged hospitalisation. There is currently insufficient data to compare the predictive validity of frailty tools in the SOT population. Conclusion Overall, there is great variability in the approach to frailty measurement in this population. Preferably, a validated frailty measurement tool would be incorporated into SOT eligibility assessments internationally with a view to facilitating comparisons between patient sub-groups and national and international transplant services with the ultimate goal of improved patient care.

Smoke from southern Africa blankets the southeastern Atlantic Ocean from June to October, producing strong and competing aerosol radiative effects. Smoke effects on the transition between overcast stratocumulus and scattered cumulus clouds are investigated along a Lagrangian (air-mass-following) trajectory in regional climate and large eddy simulation models. Results are compared with observations from three recent field campaigns that took place in August 2017: ObseRvations of Aerosols above CLouds and their intEractionS (ORACLES), CLouds and Aerosol Radiative Impacts and Forcing: Year 2017 (CLARIFY), and Layered Atlantic Smoke Interactions with Clouds (LASIC). The case study is set up around the joint ORACLES–CLARIFY flight that took place near Ascension Island on 18 August 2017. Smoke sampled upstream on an ORACLES flight on 15 August 2017 likely entrained into the marine boundary layer later sampled during the joint flight. The case is first simulated with the WRF-CAM5 regional climate model in three distinct setups: (1) FireOn, in which smoke emissions and any resulting smoke–cloud–radiation interactions are included; (2) FireOff, in which no smoke emissions are included; (3) RadOff, in which smoke emissions and their microphysical effects are included but aerosol does not interact directly with radiation. Over the course of the Lagrangian trajectory, differences in free tropospheric thermodynamic properties between FireOn and FireOff are nearly identical to those between FireOn and RadOff, showing that aerosol–radiation interactions are primarily responsible for the free tropospheric effects. These effects are non-intuitive: in addition to the expected heating within the core of the smoke plume, there is also a “banding” effect of cooler temperature (∼1–2 K) and greatly enhanced moisture (>2 g kg−1) at the plume top. This banding effect is caused by a vertical displacement of the former continental boundary layer in the free troposphere in the FireOn simulation resulting from anomalous diabatic heating due to smoke absorption of sunlight that manifests primarily as a few hundred meters per day reduction in large-scale subsidence over the ocean. A large eddy simulation (LES) is then forced with free tropospheric fields taken from the outputs for the WRF-CAM5 FireOn and FireOff runs. Cases are run by selectively perturbing one variable (e.g., aerosol number concentration, temperature, moisture, vertical velocity) at a time to better understand the contributions from different indirect (microphysical), “large-scale” semi-direct (above-cloud thermodynamic and subsidence changes), and “local” semi-direct (below-cloud smoke absorption) effects. Despite a more than 5-fold increase in cloud droplet number concentration when including smoke aerosol concentrations, minimal differences in cloud fraction evolution are simulated by the LES when comparing the base case with a perturbed aerosol case with identical thermodynamic and dynamic forcings. A factor of 2 decrease in background free tropospheric aerosol concentrations from the FireOff simulation shifts the cloud evolution from a classical entrainment-driven “deepening–warming” transition to trade cumulus to a precipitation-driven “drizzle-depletion” transition to open cells, however. The thermodynamic and dynamic changes caused by the WRF-simulated large-scale adjustments to smoke diabatic heating strongly influence cloud evolution in terms of both the rate of deepening (especially for changes in the inversion temperature jump and in subsidence) and in cloud fraction on the final day of the simulation (especially for the moisture “banding” effect). Such large-scale semi-direct effects would not have been possible to simulate using a small-domain LES model alone.

The semi-permanent stratocumulus clouds over the south-eastern Atlantic Ocean (SEA) can act as an “air conditioner” to the regional and global climate system. The interaction of aerosols and clouds becomes important in this region and can lead to negative radiative effects, partially offsetting the positive radiative forcing of greenhouse gases. A key pathway by which aerosols affect cloud properties is by acting as cloud condensation nuclei (CCN). In this paper, we use the United Kingdom Earth System Model (UKESM1) to investigate the sources of CCN (from emissions and atmospheric processes) in the SEA as well as the response of the cloud droplet number concentration (CDNC), the cloud liquid water path (LWP), and radiative forcing to these sources during 2016 and 2017. Overall, free and upper troposphere nucleated aerosols are the dominant source of the boundary layer CCN concentration at 0.2 % supersaturation (CCN0.2 %), contributing an annual average of ∼ 41 % as they subside and entrain into the marine boundary layer, which is consistent with observations highlighting the important role of nucleation in the boundary layer CCN concentration. In terms of emission sources, anthropogenic emissions (from energy, industry, agriculture, etc.) contribute the most to the annual average CCN0.2 % in the marine boundary layer (∼ 26 %), followed by biomass burning (BB, ∼ 17 %). In the cloud layer, BB contributes about 34 % of the annual CCN0.2 %, midway between the contributions from aerosol nucleation (36 %) and anthropogenic sources (31 %). The contribution of aerosols from different sources to the CDNC is consistent with their contribution to CCN0.2 % within the marine boundary layer, with free and upper troposphere aerosol nucleation being the most important source of the CDNC overall. In terms of emission sources, anthropogenic sources are also the largest contributors to the annual average CDNC, closely followed by BB. However, during the BB season, BB and free and upper troposphere aerosol nucleation are equally the most important sources of the CDNC. The contribution of BB to the CDNC is more significant than its increase to CCN0.2 %, mainly because BB aerosols are mostly located directly above the inversion layer in the model; thus, they can increase the in-cloud CDNC by enhancing the supersaturation through the dynamical feedback due to short-wave absorption. An aerosol source that shows an increase in the CDNC also shows an increase in the LWP resulting from a reduction in autoconversion. Due to the absorption effect, BB aerosol can enhance existing temperature inversions and reduce the entrainment of sub-saturated air, leading to a further increase in the LWP. As a result, the contribution of BB to the LWP is second only to aerosol nucleation on annual averages. These findings demonstrate that BB is not the dominant source of CCN within the marine boundary layer from an emission source perspective. However, as most BB aerosols are located directly above the inversion layer, their effect on clouds increases due to their absorption effect (about the same as anthropogenic sources for the CDNC and more than anthropogenic sources for the LWP), highlighting the crucial role of their radiative effect on clouds. The results on the radiative effects of aerosols show that BB aerosol exhibits an overall positive RFari (radiative forcing associated with aerosol–radiation interactions), but its net effective radiative forcing remains negative due to its effect on clouds (mainly due to its absorbing effect). By quantifying aerosol and cloud properties affected by different sources, this paper provides a framework for understanding the effects of aerosol sources on marine stratocumulus clouds and radiation in the SEA.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the commonest liver condition in the western world and is directly linked to obesity and the metabolic syndrome. Elevated body mass index is regarded as a major risk factor of NAFL (steatosis) and NAFLD fibrosis. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we sought to investigate whether other variables from adolescence could improve prediction of future NAFL and NAFLD fibrosis risk at 24 years, above BMI and sex. Methods Aged 24 years, 4018 ALSPAC participants had transient elastography (TE) and controlled attenuation parameter (CAP) measurement using Echosens 502 Touch. 513 participants with harmful alcohol consumption were excluded. Logistic regression models examined which variables measured at 17 years were predictive of NAFL and NAFLD fibrosis in young adults. Predictors included sex, BMI, central adiposity, lipid profile, blood pressure, liver function tests, homeostatic model assessment for insulin resistance (HOMA-IR), and ultrasound defined NAFL at 17 years (when examining fibrosis outcomes). A model including all these variables was termed “routine clinical measures”. Models were compared using area under the receiver operator curve (AUROC) and Bayesian Information Criterion (BIC), analysis, which penalises model complexity. Models were tested in all participants and those with overweight or obese standardised BMIs (BMI SDS) centiles at the 17-year time point. A decision curve analysis (DCA) was performed to evaluate the clinical utility of models in overweight and obese adolescents predicting NAFLD fibrosis at a threshold probability of 0.1. Results The “routine clinical measures” model had the highest AUROC for predicting NAFL in all adolescent participants (AUROC 0.79 [SD 0.00]) and those with an overweight/obese BMI SDS centile (AUROC 0.77 [SD 0.01]). According to BIC analysis, insulin resistance was the best predictor of NAFL in all adolescents, whilst central adiposity was the best predictor in those with an overweight/obese BMI SDS centile. The “routine clinical measures” model also had the highest AUROC for predicting NAFLD fibrosis in all adolescent participants (AUROC 0.78 [SD 0.02]) and participants with an overweight/obese BMI SDS centile (AUROC 0.84 [SD 0.03]). However, following BIC analysis, BMI was the best predictor of NAFLD fibrosis in all adolescents including those with an overweight/obese BMI SDS centile. A decision curve analysis examining overweight/obese adolescent participants showed the model that had the greatest net benefit for increased NAFLD fibrosis detection, above a treat all overweight and obese adolescents’ assumption, was the “routine clinical measures” model. However, the net benefit was marginal (0.0054 [0.0034–0.0075]). Conclusion In adolescents, routine clinical measures were not superior to central adiposity and BMI at predicting NAFL and NAFLD fibrosis respectively in young adulthood. Additional routine clinical measurements do provide incremental benefit in detecting true positive fibrosis cases, but the benefit is small. Thus, to reduce morbidity and mortality associated with NASH cirrhosis in adults, the ultimate end point of NAFLD, the focus must be on obesity management at a population level.

Biomass burning smoke is advected over the southeastern Atlantic Ocean between July and October of each year. This smoke plume overlies and mixes into a region of persistent low marine clouds. Model calculations of climate forcing by this plume vary significantly in both magnitude and sign. NASA EVS-2 (Earth Venture Suborbital-2) ORACLES (ObseRvations of Aerosols above CLouds and their intEractionS) had deployments for field campaigns off the west coast of Africa in 3 consecutive years (September 2016, August 2017, and October 2018) with the goal of better characterizing this plume as a function of the monthly evolution by measuring the parameters necessary to calculate the direct aerosol radiative effect. Here, this dataset and satellite retrievals of cloud properties are used to test the representation of the smoke plume and the underlying cloud layer in two regional models (WRF-CAM5 and CNRM-ALADIN) and two global models (GEOS and UM-UKCA). The focus is on the comparisons of those aerosol and cloud properties that are the primary determinants of the direct aerosol radiative effect and on the vertical distribution of the plume and its properties. The representativeness of the observations to monthly averages are tested for each field campaign, with the sampled mean aerosol light extinction generally found to be within 20 % of the monthly mean at plume altitudes. When compared to the observations, in all models, the simulated plume is too vertically diffuse and has smaller vertical gradients, and in two of the models (GEOS and UM-UKCA), the plume core is displaced lower than in the observations. Plume carbon monoxide, black carbon, and organic aerosol masses indicate underestimates in modeled plume concentrations, leading, in general, to underestimates in mid-visible aerosol extinction and optical depth. Biases in mid-visible single scatter albedo are both positive and negative across the models. Observed vertical gradients in single scatter albedo are not captured by the models, but the models do capture the coarse temporal evolution, correctly simulating higher values in October (2018) than in August (2017) and September (2016). Uncertainties in the measured absorption Ångstrom exponent were large but propagate into a negligible (<4 %) uncertainty in integrated solar absorption by the aerosol and, therefore, in the aerosol direct radiative effect. Model biases in cloud fraction, and, therefore, the scene albedo below the plume, vary significantly across the four models. The optical thickness of clouds is, on average, well simulated in the WRF-CAM5 and ALADIN models in the stratocumulus region and is underestimated in the GEOS model; UM-UKCA simulates cloud optical thickness that is significantly too high. Overall, the study demonstrates the utility of repeated, semi-random sampling across multiple years that can give insights into model biases and how these biases affect modeled climate forcing. The combined impact of these aerosol and cloud biases on the direct aerosol radiative effect (DARE) is estimated using a first-order approximation for a subset of five comparison grid boxes. A significant finding is that the observed grid box average aerosol and cloud properties yield a positive (warming) aerosol direct radiative effect for all five grid boxes, whereas DARE using the grid-box-averaged modeled properties ranges from much larger positive values to small, negative values. It is shown quantitatively how model biases can offset each other, so that model improvements that reduce biases in only one property (e.g., single scatter albedo but not cloud fraction) would lead to even greater biases in DARE. Across the models, biases in aerosol extinction and in cloud fraction and optical depth contribute the largest biases in DARE, with aerosol single scatter albedo also making a significant contribution.

Abstract Despite the reported association between diurnal variations in ambulatory blood pressure (BP) and elevated cardiovascular disease risk, little is known regarding the effects of isometric resistance training (IRT), a practical BP-lowering intervention, on ambulatory BP and morning BP surge (MBPS). Thus, we investigated whether (i) IRT causes reductions in ambulatory BP and MBPS, in young normotensives, and (ii) if there are any sex differences in these changes. Twenty normotensive individuals (mean 24-h SBP = 121 ± 7, DBP = 67 ± 6 mmHg) undertook 10-weeks of bilateral-leg IRT (4 × 2-min/2-min rest, at 20% maximum voluntary contraction (MVC) 3 days/week). Ambulatory BP and MBPS (mean systolic BP (SBP) 2 h after waking minus the lowest sleeping 1 h mean SBP) was measures pre- and post-training. There were significant reductions in 24-h ambulatory SBP in men (− 4 ± 2 mmHg, P = 0.0001) and women (− 4 ± 2 mmHg, P = 0.0001) following IRT. Significant reductions were also observed in MBPS (− 6 ± 8 mmHg, p = 0.044; − 6 ± 7 mmHg, P = 0.019), yet there were no significant differences between men and women in these changes, and 24-h ambulatory diastolic BP remained unchanged. Furthermore, a significant correlation was identified between the magnitude of the change in MBPS and the magnitude of changes in the mean 2-h SBP after waking for both men and women (men, r = 0.89, P = 0.001; women, r = 0.74, P = 0.014). These findings add further support to the idea that IRT, as practical lifestyle intervention, is effective in significantly lowering ambulatory SBP and MBPS and might reduce the incidence of adverse cardiovascular events that often occur in the morning.

Summary: Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group—robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)—at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research.

Abstract Aims While the frailty index (FI) is a continuous variable, an FI score of 0.25 has construct and predictive validity to categorise community-dwelling older adults as frail or non-frail. Our study aimed to explore which FI categories (FI scores and labels) were being used in high impact studies of adults across different care settings and why these categories were being chosen by study authors. Methods For this systematic scoping review, Medline, Cochrane and EMBASE databases were searched for studies that measured and categorised an FI. Of 1314 articles screened, 303 met the eligibility criteria (community: N = 205; residential aged care: N = 24; acute care: N = 74). For each setting, the 10 studies with the highest field-weighted citation impact (FWCI) were identified and data, including FI scores and labels and justification provided, were extracted and analysed. Results FI scores used to distinguish frail and non-frail participants varied from 0.12 to 0.45 with 0.21 and 0.25 used most frequently. Additional categories such as mildly, moderately and severely frail were defined inconsistently. The rationale for selecting particular FI scores and labels were reported in most studies, but were not always relevant. Conclusions High impact studies vary in the way they categorise the FI and while there is some evidence in the community-dweller literature, FI categories have not been well validated in acute and residential aged care. For the time being, in those settings, the FI should be reported as a continuous variable wherever possible. It is important to continue working towards defining frailty categories as variability in FI categorisation impacts the ability to synthesise results and to translate findings into clinical practice.

Abstract Background Structured reporting is an efficient and replicable method of presenting diagnostic results that eliminates variability inherent in narrative descriptive reporting and may improve clinical decisions. Synoptic element reporting can generate discrete coded data that then may inform clinical decision support and trigger downstream actions in computerized electronic health records. Objective Limited evidence exists for use of synoptic reporting for computed tomography pulmonary arteriography (CTPA) among patients suspected of pulmonary embolism. We reported the accuracy of synoptic reporting for the outcome of pulmonary embolism among patients who presented to an integrated health care system with CTPA performed for suspected pulmonary embolism. Methods Structured radiology reports with embedded synoptic elements were implemented for all CTPA examinations on March 1, 2018. Four hundred CTPA reports between January 4, 2019 and July 30, 2020 (200 reports each for which synoptic reporting recorded the presence or absence of pulmonary embolism [PE]) were selected at random. One non‐diagnostic study was excluded from analysis. We then assessed the accuracy of synoptic reporting compared with the gold standard of manual chart review. Results Synoptic reporting and manual review agreed in 99.2% of patients undergoing CTPA for suspected PE, agreed on the presence of PE in 196 of 199 (98.5%) cases, the absence of PE in 200 of 200 (100%) cases with a sensitivity of 87.6% (76.1–96.1) a specificity of 99.9% (99.7%–100%), a positive predictive value of 99.5% (98.1–100), and a negative predictive value of 98% (95.7%–99.5%). Conclusion The overall rate of agreement was 99.2%, but we observed an unacceptable false‐negative rate for clinical reliance on synoptic element reporting in isolation from dictated reports.

New particle formation (NPF) is a significant source of atmospheric particles, affecting climate and air quality. Understanding the mechanisms involved in urban aerosols is important to develop effective mitigation strategies. However, NPF rates reported in the polluted boundary layer span more than 4 orders of magnitude, and the reasons behind this variability are the subject of intense scientific debate. Multiple atmospheric vapours have been postulated to participate in NPF, including sulfuric acid, ammonia, amines and organics, but their relative roles remain unclear. We investigated NPF in the CLOUD chamber using mixtures of anthropogenic vapours that simulate polluted boundary layer conditions. We demonstrate that NPF in polluted environments is largely driven by the formation of sulfuric acid–base clusters, stabilized by the presence of amines, high ammonia concentrations and lower temperatures. Aromatic oxidation products, despite their extremely low volatility, play a minor role in NPF in the chosen urban environment but can be important for particle growth and hence for the survival of newly formed particles. Our measurements quantitatively account for NPF in highly diverse urban environments and explain its large observed variability. Such quantitative information obtained under controlled laboratory conditions will help the interpretation of future ambient observations of NPF rates in polluted atmospheres.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a growing class of natural products biosynthesized from a genetically encoded precursor peptide. The enzymes that install the post-translational modifications on these peptides have the potential to be useful catalysts in the production of natural-product-like compounds and can install non-proteogenic amino acids in peptides and proteins. However, engineering these enzymes has been somewhat limited, due in part to limited structural information on enzymes in the same families that nonetheless exhibit different substrate selectivities. Despite AlphaFold2’s superior performance in single-chain protein structure prediction, its multimer version lacks accuracy and requires high-end GPUs, which are not typically available to most research groups. Additionally, the default parameters of AlphaFold2 may not be optimal for predicting complex structures like RiPP biosynthetic enzymes, due to their dynamic binding and substrate-modifying mechanisms. This study assessed the efficacy of the structure prediction program ColabFold (a variant of AlphaFold2) in modeling RiPP biosynthetic enzymes in both monomeric and dimeric forms. After extensive benchmarking, it was found that there were no statistically significant differences in the accuracy of the predicted structures, regardless of the various possible prediction parameters that were examined, and that with the default parameters, ColabFold was able to produce accurate models. We then generated additional structural predictions for select RiPP biosynthetic enzymes from multiple protein families and biosynthetic pathways. Our findings can serve as a reference for future enzyme engineering complemented by AlphaFold-related tools.

We present the first space-borne observation of optical emissions of both neutral and ionized argon atoms resulting from a radio-frequency glow discharge (RF-GD) from a sounding rocket payload. The Observations of Electric-field Distributions in the Ionospheric Plasma--a Unique Strategy-C (OEDIPUS-C) payload was designed to separate into two sub-payloads 'on its up-leg. This separation permitted a number of two-point measurements, including those on radio wave propagation' from the active dipole antennas on the upper sub-payload to the synchronized receiving dipoles on the lower sub-payload. A white-light video camera on the lower sub-payload recorded strong luminosity around the active dipoles during the first 15 s 'after sub-payload separation, when argon gas jets were providing propulsion to separate the two sub-payloads. Parts of the' ejected argon appeared as a glowing volume where the large radio-frequency (RF) fields from the two active dipoles excited 'the optical emission, as the sub-payload separation increased from 2 to 55 m. The shape and intensity of the luminosity were' 'well repeated as a function of the swept frequency (0.025-8.000 MHz), but their frequency dependences were distinctly differ-' 'ent from those of sounder-accelerated electrons measured onboard, and deduced to result from the nonlinearity of the glow' 'discharge. The observation is to our knowledge the first of its kind, and is interpreted in terms of a RF-GD energized by the' strong near electric fields of the transmitting dipoles. Key words: ionosphere, radio-frequency glow discharge, argon, sounding rocket, optical emission.' Nous presentons les premieres observations sur plateforme spatiale des emissions optiques d'atomes d'argon neutres et ionises resultant d'une decharge luminescente radiofrequence (DL-RF/RF-GD) generee par l'instrument d'une fusee sonde. L'instrument embarque Observation of Electric field Distribution in the Ionospheric Plasma--a Unique Strategy-C (OEDIPUS-C) a ete concu pour se separer verticalement en deux sous-instruments (inferieur et superieur). Cette separation permet un nombre de mesures en deux points, incluant une mesure de la propagation des ondes radio venant des antennes dipolaires actives de l'instrument superieur vers les dipoles synchrones de l'instrument inferieur. Une camera video en lumiere blanche sur l'instrument inferieur a enregistre une forte luminosite autour des dipoles actifs pendant les 15 s apres la separation des instruments, alors que le gaz d'argon fournissait la poussee pour separer les deux sous-instruments. Une partie du gaz d'argon ejecte apparait comme un volume luminescent ou les forts champs RF provenant des deux dipoles actifs excitent l'emission optique, pendant que la separation des instruments passe de 2 m a 55 m. La forme et l'intensite de cette lumiere sont bien representees comme une fonction de la frequence de balayage (0.025-8.000 MHz), mais leurs dependances en frequence sont nettement differentes de celles des electrons acceleres du sondeur mesurees a bord et on en deduit que cela resulte de la non linearite de la decharge luminescente. Cette observation est, a notre connaissance, la premiere de son type et est interpretee en termes de decharge luminescente radiofrequence stimulee par les forts champs electriques emanant des dipoles de transmission. [Traduit par la Redaction] Mots-cles : ionosphere, decharge luminescente radiofrequence (DL-RF), argon, fusee sonde, emission optique, 1. Introduction Two television cameras with a spectral response between 400 and 900 nm were installed on the Observations of Electric-field Distributions in the Ionospheric Plasma--a Unique Strategy-C (OEDIPUS-C, OC [...]

Understanding the vertical distribution of aerosol helps to reduce the uncertainty in the aerosol life cycle and therefore in the estimation of the direct and indirect aerosol forcing. To improve our understanding, we use measurements from four deployments of the Atmospheric Tomography (ATom) field campaign (ATom1–4) which systematically sampled aerosol and trace gases over the Pacific and Atlantic oceans with near pole-to-pole coverage. We evaluate the UK Earth System Model (UKESM1) against ATom observations in terms of joint biases in the vertical profile of three variables related to new particle formation: total particle number concentration (NTotal), sulfur dioxide (SO2) mixing ratio and the condensation sink. The NTotal, SO2 and condensation sink are interdependent quantities and have a controlling influence on the vertical profile of each other; therefore, analysing them simultaneously helps to avoid getting the right answer for the wrong reasons. The simulated condensation sink in the baseline model is within a factor of 2 of observations, but the NTotal and SO2 show much larger biases mainly in the tropics and high latitudes. We performed a series of model sensitivity tests to identify atmospheric processes that have the strongest influence on overall model performance. The perturbations take the form of global scaling factors or improvements to the representation of atmospheric processes in the model, for example by adding a new boundary layer nucleation scheme. In the boundary layer (below 1 km altitude) and lower troposphere (1–4 km), inclusion of a boundary layer nucleation scheme (Metzger et al., 2010) is critical to obtaining better agreement with observations. However, in the mid (4–8 km) and upper troposphere (> 8 km), sub-3 nm particle growth, pH of cloud droplets, dimethyl sulfide (DMS) emissions, upper-tropospheric nucleation rate, SO2 gas-scavenging rate and cloud erosion rate play a more dominant role. We find that perturbations to boundary layer nucleation, sub-3 nm growth, cloud droplet pH and DMS emissions reduce the boundary layer and upper tropospheric model bias simultaneously. In a combined simulation with all four perturbations, the SO2 and condensation sink profiles are in much better agreement with observations, but the NTotal profile still shows large deviations, which suggests a possible structural issue with how nucleation or gas/particle transport or aerosol scavenging is handled in the model. These perturbations are well-motivated in that they improve the physical basis of the model and are suitable for implementation in future versions of UKESM.

The representations of clouds, aerosols, and cloud–aerosol–radiation impacts remain some of the largest uncertainties in climate change, limiting our ability to accurately reconstruct past climate and predict future climate. The south-east Atlantic is a region where high atmospheric aerosol loadings and semi-permanent stratocumulus clouds are co-located, providing an optimum region for studying the full range of aerosol–radiation and aerosol–cloud interactions and their perturbations of the Earth's radiation budget. While satellite measurements have provided some useful insights into aerosol–radiation and aerosol–cloud interactions over the region, these observations do not have the spatial and temporal resolution, nor the required level of precision to allow for a process-level assessment. Detailed measurements from high spatial and temporal resolution airborne atmospheric measurements in the region are very sparse, limiting their use in assessing the performance of aerosol modelling in numerical weather prediction and climate models. CLARIFY-2017 was a major consortium programme consisting of five principal UK universities with project partners from the UK Met Office and European- and USA-based universities and research centres involved in the complementary ORACLES, LASIC, and AEROCLO-sA projects. The aims of CLARIFY-2017 were fourfold: (1) to improve the representation and reduce uncertainty in model estimates of the direct, semi-direct, and indirect radiative effect of absorbing biomass burning aerosols; (2) to improve our knowledge and representation of the processes determining stratocumulus cloud microphysical and radiative properties and their transition to cumulus regimes; (3) to challenge, validate, and improve satellite retrievals of cloud and aerosol properties and their radiative impacts; (4) to improve the impacts of aerosols in weather and climate numerical models. This paper describes the modelling and measurement strategies central to the CLARIFY-2017 deployment of the FAAM BAe146 instrumented aircraft campaign, summarizes the flight objectives and flight patterns, and highlights some key results from our initial analyses.

The south-eastern Atlantic Ocean (SEA) is semi-permanently covered by one of the most extensive stratocumulus cloud decks on the planet and experiences about one-third of the global biomass burning emissions from the southern Africa savannah region during the fire season. To get a better understanding of the impact of these biomass burning aerosols on clouds and the radiation balance over the SEA, the latest generation of the UK Earth System Model (UKESM1) is employed. Measurements from the CLARIFY and ORACLES flight campaigns are used to evaluate the model, demonstrating that the model has good skill in reproducing the biomass burning plume. To investigate the underlying mechanisms in detail, the effects of biomass burning aerosols on the clouds are decomposed into radiative effects (via absorption and scattering) and microphysical effects (via perturbation of cloud condensation nuclei – CCN – and cloud microphysical processes). July–August means are used to characterize aerosols, clouds, and the radiation balance during the fire season. Results show that around 65 % of CCN at 0.2 % supersaturation in the SEA can be attributed to biomass burning. The absorption effect of biomass burning aerosols is the most significant on clouds and radiation. Near the continent, it increases the supersaturation diagnosed by the activation scheme, while further from the continent it reduces the altitude of the supersaturation. As a result, the cloud droplet number concentration responds with a similar pattern to the absorption effect of biomass burning aerosols. The microphysical effect, however, decreases the supersaturation and increases the cloud droplet concentration over the ocean, although this change is relatively small. The liquid water path is also significantly increased over the SEA (mainly caused by the absorption effect of biomass burning aerosols) when biomass burning aerosols are above the stratocumulus cloud deck. The microphysical pathways lead to a slight increase in the liquid water path over the ocean. These changes in cloud properties indicate the significant role of biomass burning aerosols for clouds in this region. Among the effects of biomass burning aerosols on the radiation balance, the semi-direct radiative effects (rapid adjustments induced by the radiative effects of biomass burning aerosols) have a dominant cooling impact over the SEA, which offset the warming direct radiative effect (radiative forcing from biomass burning aerosol–radiation interactions) and lead to an overall net cooling radiative effect in the SEA. However, the magnitude and the sign of the semi-direct effects are sensitive to the relative location of biomass burning aerosols and clouds, reflecting the critical task of the accurate modelling of the biomass burning plume and clouds in this region.

Nucleation of atmospheric vapours produces more than half of global cloud condensation nuclei and so has an important influence on climate. Recent studies show that monoterpene (C10H16) oxidation yields highly oxygenated products that can nucleate with or without sulfuric acid. Monoterpenes are emitted mainly by trees, frequently together with isoprene (C5H8), which has the highest global emission of all organic vapours. Previous studies have shown that isoprene suppresses new-particle formation from monoterpenes, but the cause of this suppression is under debate. Here, in experiments performed under atmospheric conditions in the CERN CLOUD chamber, we show that isoprene reduces the yield of highly oxygenated dimers with 19 or 20 carbon atoms – which drive particle nucleation and early growth – while increasing the production of dimers with 14 or 15 carbon atoms. The dimers (termed C20 and C15, respectively) are produced by termination reactions between pairs of peroxy radicals (RO2⚫) arising from monoterpenes or isoprene. Compared with pure monoterpene conditions, isoprene reduces nucleation rates at 1.7 nm (depending on the isoprene ∕ monoterpene ratio) and approximately halves particle growth rates between 1.3 and 3.2 nm. However, above 3.2 nm, C15 dimers contribute to secondary organic aerosol, and the growth rates are unaffected by isoprene. We further show that increased hydroxyl radical (OH⚫) reduces particle formation in our chemical system rather than enhances it as previously proposed, since it increases isoprene-derived RO2⚫ radicals that reduce C20 formation. RO2⚫ termination emerges as the critical step that determines the highly oxygenated organic molecule (HOM) distribution and the corresponding nucleation capability. Species that reduce the C20 yield, such as NO, HO2 and as we show isoprene, can thus effectively reduce biogenic nucleation and early growth. Therefore the formation rate of organic aerosol in a particular region of the atmosphere under study will vary according to the precise ambient conditions.

In the southeast Atlantic, well-defined smoke plumes from Africa advect over marine boundary layer cloud decks; both are most extensive around September, when most of the smoke resides in the free troposphere. A framework is put forth for evaluating the performance of a range of global and regional atmospheric composition models against observations made during the NASA ORACLES (ObseRvations of Aerosols above CLouds and their intEractionS) airborne mission in September 2016. A strength of the comparison is a focus on the spatial distribution of a wider range of aerosol composition and optical properties than has been done previously. The sparse airborne observations are aggregated into approximately 2∘ grid boxes and into three vertical layers: 3–6 km, the layer from cloud top to 3 km, and the cloud-topped marine boundary layer. Simulated aerosol extensive properties suggest that the flight-day observations are reasonably representative of the regional monthly average, with systematic deviations of 30 % or less. Evaluation against observations indicates that all models have strengths and weaknesses, and there is no single model that is superior to all the others in all metrics evaluated. Whereas all six models typically place the top of the smoke layer within 0–500 m of the airborne lidar observations, the models tend to place the smoke layer bottom 300–1400 m lower than the observations. A spatial pattern emerges, in which most models underestimate the mean of most smoke quantities (black carbon, extinction, carbon monoxide) on the diagonal corridor between 16∘ S, 6∘ E, and 10∘ S, 0∘ E, in the 3–6 km layer, and overestimate them further south, closer to the coast, where less aerosol is present. Model representations of the above-cloud aerosol optical depth differ more widely. Most models overestimate the organic aerosol mass concentrations relative to those of black carbon, and with less skill, indicating model uncertainties in secondary organic aerosol processes. Regional-mean free-tropospheric model ambient single scattering albedos vary widely, between 0.83 and 0.93 compared with in situ dry measurements centered at 0.86, despite minimal impact of humidification on particulate scattering. The modeled ratios of the particulate extinction to the sum of the black carbon and organic aerosol mass concentrations (a mass extinction efficiency proxy) are typically too low and vary too little spatially, with significant inter-model differences. Most models overestimate the carbonaceous mass within the offshore boundary layer. Overall, the diversity in the model biases suggests that different model processes are responsible. The wide range of model optical properties requires further scrutiny because of their importance for radiative effect estimates.

We present here results from a new mechanism, CRI-HOM, which we have developed to simulate the formation of highly oxygenated organic molecules (HOMs) from the gas-phase oxidation of α-pinene, one of the most widely emitted biogenic volatile organic compounds (BVOCs) by mass. This concise scheme adds 12 species and 66 reactions to the Common Representative Intermediates (CRI) mechanism v2.2 Reduction 5 and enables the representation of semi-explicit HOM treatment suitable for long-term global chemistry–aerosol–climate modelling, within a comprehensive tropospheric chemical mechanism. The key features of the new mechanism are (i) representation of the autoxidation of peroxy radicals from the hydroxyl radical and ozone initiated reactions of α-pinene, (ii) formation of multiple generations of peroxy radicals, (iii) formation of accretion products (dimers), and (iv) isoprene-driven suppression of accretion product formation, as observed in experiments. The mechanism has been constructed through optimisation against a series of flow tube laboratory experiments. The mechanism predicts a HOM yield of 2 %–4.5 % under conditions of low to moderate NOx, in line with experimental observations, and reproduces qualitatively the decline in HOM yield and concentration at higher NOx levels. The mechanism gives a HOM yield that also increases with temperature, in line with observations, and our mechanism compares favourably to some of the limited observations of [HOM] observed in the boreal forest in Finland and in the southeast USA. The reproduction of isoprene-driven suppression of HOMs is a key step forward as it enables global climate models to capture the interaction between the major BVOC species, along with the potential climatic feedbacks. This suppression is demonstrated when the mechanism is used to simulate atmospheric profiles over the boreal forest and rainforest; different isoprene concentrations result in different [HOM] distributions, illustrating the importance of BVOC interactions in atmospheric composition and climate. Finally particle nucleation rates calculated from [HOM] in present-day and pre-industrial atmospheres suggest that “sulfuric-acid-free” nucleation can compete effectively with other nucleation pathways in the boreal forest, particularly in the pre-industrial period, with important implications for the aerosol budget and radiative forcing.

Representing the number and mass of cloud and aerosol particles independently in a climate, weather prediction or air quality model is important in order to simulate aerosol direct and indirect effects on radiation balance. Here we introduce the first configuration of the UK Met Office Unified Model in which both cloud and aerosol particles have “double-moment” representations with prognostic number and mass. The GLObal Model of Aerosol Processes (GLOMAP) aerosol microphysics scheme, already used in the Hadley Centre Global Environmental Model version 3 (HadGEM3) climate configuration, is coupled to the Cloud AeroSol Interacting Microphysics (CASIM) cloud microphysics scheme. We demonstrate the performance of the new configuration in high-resolution simulations of a case study defined from the CLARIFY aircraft campaign in 2017 near Ascension Island in the tropical southern Atlantic. We improve the physical basis of the activation scheme by representing the effect of existing cloud droplets on the activation of new aerosol, and we also discuss the effect of unresolved vertical velocities. We show that neglect of these two competing effects in previous studies led to compensating errors but realistic droplet concentrations. While these changes lead only to a modest improvement in model performance, they reinforce our confidence in the ability of the model microphysics code to simulate the aerosol–cloud microphysical interactions it was designed to represent. Capturing these interactions accurately is critical to simulating aerosol effects on climate.

Conjoined nerve roots are an infrequent and uncommon finding, rarely noted preoperatively. The conjoined root anomaly has potential for significant neurological injury during surgery. Preoperative recognition may avert disastrous nerve root injury but requires a high degree of clinical suspicion. We present the case of a 44-year-old patient with left L5/S1 radiculopathy caused by a herniated disc. During surgery we identified a triple conjoined nerve root anatomy. This anatomical variant, to our knowledge, has not been reported in literature. We describe the anatomical findings and surgical implications.

Highly oxygenated organic molecules (HOMs) contribute substantially to the formation and growth of atmospheric aerosol particles, which affect air quality, human health and Earth's climate. HOMs are formed by rapid, gas-phase autoxidation of volatile organic compounds (VOCs) such as α-pinene, the most abundant monoterpene in the atmosphere. Due to their abundance and low volatility, HOMs can play an important role in new-particle formation (NPF) and the early growth of atmospheric aerosols, even without any further assistance of other low-volatility compounds such as sulfuric acid. Both the autoxidation reaction forming HOMs and their NPF rates are expected to be strongly dependent on temperature. However, experimental data on both effects are limited. Dedicated experiments were performed at the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber at CERN to address this question. In this study, we show that a decrease in temperature (from +25 to −50 ∘C) results in a reduced HOM yield and reduced oxidation state of the products, whereas the NPF rates (J1.7 nm) increase substantially. Measurements with two different chemical ionization mass spectrometers (using nitrate and protonated water as reagent ion, respectively) provide the molecular composition of the gaseous oxidation products, and a two-dimensional volatility basis set (2D VBS) model provides their volatility distribution. The HOM yield decreases with temperature from 6.2 % at 25 ∘C to 0.7 % at −50 ∘C. However, there is a strong reduction of the saturation vapor pressure of each oxidation state as the temperature is reduced. Overall, the reduction in volatility with temperature leads to an increase in the nucleation rates by up to 3 orders of magnitude at −50 ∘C compared with 25 ∘C. In addition, the enhancement of the nucleation rates by ions decreases with decreasing temperature, since the neutral molecular clusters have increased stability against evaporation. The resulting data quantify how the interplay between the temperature-dependent oxidation pathways and the associated vapor pressures affect biogenic NPF at the molecular level. Our measurements, therefore, improve our understanding of pure biogenic NPF for a wide range of tropospheric temperatures and precursor concentrations.

In the present-day atmosphere, sulfuric acid is the most important vapour for aerosol particle formation and initial growth. However, the growth rates of nanoparticles ( nm) from sulfuric acid remain poorly measured. Therefore, the effect of stabilizing bases, the contribution of ions and the impact of attractive forces on molecular collisions are under debate. Here, we present precise growth rate measurements of uncharged sulfuric acid particles from 1.8 to 10 nm, performed under atmospheric conditions in the CERN (European Organization for Nuclear Research) CLOUD chamber. Our results show that the evaporation of sulfuric acid particles above 2 nm is negligible, and growth proceeds kinetically even at low ammonia concentrations. The experimental growth rates exceed the hard-sphere kinetic limit for the condensation of sulfuric acid. We demonstrate that this results from van der Waals forces between the vapour molecules and particles and disentangle it from charge–dipole interactions. The magnitude of the enhancement depends on the assumed particle hydration and collision kinetics but is increasingly important at smaller sizes, resulting in a steep rise in the observed growth rates with decreasing size. Including the experimental results in a global model, we find that the enhanced growth rate of sulfuric acid particles increases the predicted particle number concentrations in the upper free troposphere by more than 50 %.

Aerosol–cloud interactions represent the leading uncertainty in our ability to infer climate sensitivity from the observational record. The forcing from changes in cloud albedo driven by increases in cloud droplet number (Nd) (the first indirect effect) is confidently negative and has narrowed its probable range in the last decade, but the sign and strength of forcing associated with changes in cloud macrophysics in response to aerosol (aerosol–cloud adjustments) remain uncertain. This uncertainty reflects our inability to accurately quantify variability not associated with a causal link flowing from the cloud microphysical state to the cloud macrophysical state. Once variability associated with meteorology has been removed, covariance between the liquid water path (LWP) averaged across cloudy and clear regions (here characterizing the macrophysical state) and Nd (characterizing the microphysical) is the sum of two causal pathways linking Nd to LWP: Nd altering LWP (adjustments) and precipitation scavenging aerosol and thus depleting Nd. Only the former term is relevant to constraining adjustments, but disentangling these terms in observations is challenging. We hypothesize that the diversity of constraints on aerosol–cloud adjustments in the literature may be partly due to not explicitly characterizing covariance flowing from cloud to aerosol and aerosol to cloud. Here, we restrict our analysis to the regime of extratropical clouds outside of low-pressure centers associated with cyclonic activity. Observations from MAC-LWP (Multisensor Advanced Climatology of Liquid Water Path) and MODIS are compared to simulations in the Met Office Unified Model (UM) GA7.1 (the atmosphere model of HadGEM3-GC3.1 and UKESM1). The meteorological predictors of LWP are found to be similar between the model and observations. There is also agreement with previous literature on cloud-controlling factors finding that increasing stability, moisture, and sensible heat flux enhance LWP, while increasing subsidence and sea surface temperature decrease it. A simulation where cloud microphysics are insensitive to changes in Nd is used to characterize covariance between Nd and LWP that is induced by factors other than aerosol–cloud adjustments. By removing variability associated with meteorology and scavenging, we infer the sensitivity of LWP to changes in Nd. Application of this technique to UM GA7.1 simulations reproduces the true model adjustment strength. Observational constraints developed using simulated covariability not induced by adjustments and observed covariability between Nd and LWP predict a 25 %–30 % overestimate by the UM GA7.1 in LWP change and a 30 %–35 % overestimate in associated radiative forcing.

Background Oral microbiota are thought to influence blood pressure (BP) regulation. However, epidemiological data supporting this hypothesis are limited. We examined associations between oral microbiota, BP, and incident hypertension in postmenopausal women. Methods and Results Baseline (1997–2001) examinations were completed on 1215 women (mean age, 63 years) during which subgingival plaque was collected, BP was measured, and medical and lifestyle histories and medication inventory were obtained. Microbiome composition of subgingival plaque was measured using 16S ribosomal RNA gene amplicon sequencing. Baseline measured BP was defined as normotensive (systolic

Weight stigma is widely accepted by society and may be difficult to reduce through externally motivating factors. It is important to also investigate internally motivated factors that may be associated with the choice to engage in weight-based victimization such as dispositional empathy and its association to attitudinal weight bias. Our hypotheses were: 1) individuals with higher empathy would report engaging in less victimization; 2) this would be explained by these individuals having less attitudinal weight bias and the belief that individuals are not to blame for their weight. A regression analysis (N = 284) revealed that empathy significantly predicted reported victimization behaviors, with higher levels of trait empathy associated with less victimization. An indirect effect analysis revealed that trait empathy had an indirect effect on victimization via “obesity” beliefs, but not attitudinal weight bias. Findings suggest that interventions designed with psychoeducation about “obesity” beliefs may aid in weight biased-behavior reduction.

This erratum corrects measurements of the prompt and secondary (from-b).

The interannual variability of the greenhouse gases methane (CH4) and tropospheric ozone (O3) is largely driven by natural variations in global emissions and meteorology. The El Niño–Southern Oscillation (ENSO) is known to influence fire occurrence, wetland emission and atmospheric circulation, affecting sources and sinks of CH4 and tropospheric O3, but there are still important uncertainties associated with the exact mechanism and magnitude of this effect. Here we use a modelling approach to investigate how fires and meteorology control the interannual variability of global carbon monoxide (CO), CH4 and O3 concentrations, particularly during large El Niño events. Using a three-dimensional chemical transport model (TOMCAT) coupled to a sophisticated aerosol microphysics scheme (GLOMAP) we simulate changes to CO, hydroxyl radical (OH) and O3 for the period 1997–2014. We then use an offline radiative transfer model to quantify the climate impact of changes to atmospheric composition as a result of specific drivers. During the El Niño event of 1997–1998, there were increased emissions from biomass burning globally, causing global CO concentrations to increase by more than 40 %. This resulted in decreased global mass-weighted tropospheric OH concentrations of up to 9 % and a consequent 4 % increase in the CH4 atmospheric lifetime. The change in CH4 lifetime led to a 7.5 ppb yr−1 increase in the global mean CH4 growth rate in 1998. Therefore, biomass burning emission of CO could account for 72 % of the total effect of fire emissions on CH4 growth rate in 1998. Our simulations indicate that variations in fire emissions and meteorology associated with El Niño have opposing impacts on tropospheric O3 burden. El Niño-related changes in atmospheric transport and humidity decrease global tropospheric O3 concentrations leading to a −0.03 W m−2 change in the O3 radiative effect (RE). However, enhanced fire emission of precursors such as nitrogen oxides (NOx) and CO increase O3 and lead to an O3 RE of 0.03 W m−2. While globally the two mechanisms nearly cancel out, causing only a small change in global mean O3 RE, the regional changes are large – up to −0.33 W m−2 with potentially important consequences for atmospheric heating and dynamics.

Purpose: Suicidal ideation and attempts in youth are a growing health concern, and more data are needed regarding their biological underpinnings. Asthma is a common chronic inflammatory disorder in youth and has been associated with suicidal ideation and attempts in adolescent and adult populations, but data in younger children and early adolescents are lacking. We wished to study associations of asthma with childhood suicidality considering asthma’s potential as a clinically relevant model for childhood chronic immune dysregulation. Methods: Using data from the Adolescent Brain Cognitive Development (ABCD) Study (n = 11,876, 47.8% female, mean age 9.9 years at baseline assessment and 12.0 years at two-year follow-up), we assessed associations between asthma and suicidal ideation and attempts through baseline to two-year follow-up. Results: Asthma history as defined by parent report (n = 2282, 19.2% of study population) was associated with suicide attempts (SA) (odds ratio (OR) = 1.44, p = 0.01), and this association remained significant even when controlling for demographics, socioeconomic factors, and environmental factors (OR = 1.46, p = 0.028). History of asthma attacks was associated with both suicidal ideation (SI) and SA when controlling for demographics, socioeconomic factors, and environmental factors (OR = 1.27, p = 0.042; OR = 1.83, p = 0.004, respectively). The association of asthma attack with SA remained significant when controlling for self-reported psychopathology (OR = 1.92, p = 0.004). The total number of asthma attacks was associated with both SI and SA (OR = 1.03, p = 0.043; OR = 1.06, p = 0.05, respectively). Conclusions: Findings suggest an association between asthma and suicidality in early adolescence. Further research is needed to investigate mechanisms underlying this relationship.