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Microbial carbon use efficiency (CUE) affects the fate and storage of carbon in terrestrial ecosystems, but its global importance remains uncertain. Accurately modeling and predicting CUE on a global scale is challenging due to inconsistencies in measurement techniques and the complex interactions of climatic, edaphic, and biological factors across scales. The link between microbial CUE and soil organic carbon relies on the stabilization of microbial necromass within soil aggregates or its association with minerals, necessitating an integration of microbial and stabilization processes in modeling approaches. In this perspective, we propose a comprehensive framework that integrates diverse data sources, ranging from genomic information to traditional soil carbon assessments, to refine carbon cycle models by incorporating variations in CUE, thereby enhancing our understanding of the microbial contribution to carbon cycling.

Spencer J Keene,1–3 Rachel E Jordan,1 Frits ME Franssen,3,4 Frank de Vries,2,5 James Martin,1 Alice Sitch,1,6 Alice Margaret Turner,1 Andrew P Dickens,1 David Fitzmaurice,7 Peymane Adab1 1Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK; 2Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Center+, Maastricht, the Netherlands; 3Ciro, Horn, the Netherlands; 4Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands; 5Utrecht Institute for Pharmaceutical Sciences Utrecht University, Utrecht, The Netherlands; 6NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK; 7Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UKCorrespondence: Rachel E JordanInstitute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UKTel +44 0121 414 6775Email r.e.jordan@bham.ac.ukBackground: Reviews suggest that the ADO score is the most discriminatory prognostic score for predicting mortality among chronic obstructive pulmonary disease (COPD) patients, but a full evaluation and external validation within primary care settings is critical before implementation.Objectives: To validate the ADO score in prevalent and screen-detected primary care COPD cases at 3 years and at shorter time periods.Patients and methods: One thousand eight hundred and ninety-two COPD cases were recruited between 2012 and 2014 from 71 United Kingdom general practices as part of the Birmingham COPD Cohort study. Cases were either on the practice COPD register or screen-detected. We validated the ADO score for predicting 3-year mortality with 1-year and 2-year mortality as secondary endpoints using discrimination (area-under-the-curve (AUC)) and calibration plots.Results: One hundred and fifty-four deaths occurred within 3 years. The ADO score was discriminatory for predicting 3-year mortality (AUC= 0.74; 95% CI: 0.69–0.79). Similar performance was found for 1- (AUC= 0.73; 0.66–0.80) and 2-year mortality (0.72; 0.67–0.76). The ADO score showed reasonable calibration for predicting 3-year mortality (calibration slope 0.95; 0.70–1.19) but over-predicted in cases with higher predicted risks of mortality at 1 (0.79; 0.45–1.13) and 2-year (0.79; 0.57–1.01) mortality.Discussion: The ADO score showed promising discrimination in predicting 3-year mortality in a primary care population including screen-detected cases. It may need to be recalibrated if it is used to provide risk predictions for 1- or 2-year mortality since, in these time-periods, over-prediction was evident, especially in cases with higher predicted mortality risks.Keywords: pulmonary disease, chronic obstructive, mortality, prognosis, validation studies

Martin R Miller,1 Shamil Haroon,1 Rachel E Jordan,1 Alice J Sitch,1 Andrew P Dickens,1 Alexandra Enocson,1 David A Fitzmaurice,2 Peymané Adab1 1Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK; 2Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK Background: Consensus on the definition of airflow obstruction to diagnose COPD remains unresolved.Methods: We undertook systematic case finding for COPD in primary care using the fixed ratio (FR) criterion (forced expiratory volume in 1 s/forced vital capacity [FEV1/FVC]

Kiran K Rai,1 Rachel E Jordan,1 W Stanley Siebert,2 Steven S Sadhra,3 David A Fitzmaurice,1 Alice J Sitch,1 Jon G Ayres,1,3 Peymané Adab1 1Institute of Applied Health Research, 2The Department of Business and Labour Economics, 3Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, UK Background: Employment rates among those with chronic obstructive pulmonary disease (COPD) are lower than those without COPD, but little is known about the factors that affect COPD patients’ ability to work. Methods: Multivariable analysis of the Birmingham COPD Cohort Study baseline data was used to assess the associations between lifestyle, clinical, and occupational characteristics and likelihood of being in paid employment among working-age COPD patients. Results: In total, 608 of 1,889 COPD participants were of working age, of whom 248 (40.8%) were in work. Older age (60–64 years vs 30–49 years: odds ratio [OR] =0.28; 95% confidence interval [CI] =0.12–0.65), lower educational level (no formal qualification vs degree/higher level: OR =0.43; 95% CI =0.19–0.97), poorer prognostic score (highest vs lowest quartile of modified body mass index, airflow obstruction, dyspnea, and exercise (BODE) score: OR =0.10; 95% CI =0.03–0.33), and history of high occupational exposure to vapors, gases, dusts, or fumes (VGDF; high VGDF vs no VGDF exposure: OR =0.32; 95% CI =0.12–0.85) were associated with a lower probability of being employed. Only the degree of breathlessness of BODE was significantly associated with employment. Conclusion: This is the first study to comprehensively assess the characteristics associated with employment in a community sample of people with COPD. Future interventions should focus on managing breathlessness and reducing occupational exposures to VGDF to improve the work capability among those with COPD. Keywords: chronic obstructive pulmonary disease, work, employed, breathlessness, severity, VGDF, UK

Plants with the C4 photosynthesis pathway typically respond to climate change differently from more common C3-type plants, due to their distinct anatomical and biochemical characteristics. These different responses are expected to drive changes in global C4 and C3 vegetation distributions. However, current C4 vegetation distribution models may not predict this response as they do not capture multiple interacting factors and often lack observational constraints. Here, we used global observations of plant photosynthetic pathways, satellite remote sensing, and photosynthetic optimality theory to produce an observation-constrained global map of C4 vegetation. We find that global C4 vegetation coverage decreased from 17.7% to 17.1% of the land surface during 2001 to 2019. This was the net result of a reduction in C4 natural grass cover due to elevated CO2 favoring C3-type photosynthesis, and an increase in C4 crop cover, mainly from corn (maize) expansion. Using an emergent constraint approach, we estimated that C4 vegetation contributed 19.5% of global photosynthetic carbon assimilation, a value within the range of previous estimates (18-23%) but higher than the ensemble mean of dynamic global vegetation models (14 ± 13%; mean ± one standard deviation). Our study sheds insight on the critical and underappreciated role of C4 plants in the contemporary global carbon cycle.

Surface ozone monitoring sites in the tropics are limited, despite the risk that surface ozone poses to human health, tropical forest and crop productivity. Atmospheric chemistry models allow us to assess ozone exposure in unmonitored locations and evaluate the potential influence of changing policies and climate on air quality, human health and ecosystem integrity. Here, we utilise in situ ozone measurements from ground-based stations in the pan-tropics to evaluate ozone from the UK Earth system model, UKESM1, with a focus on remote sites. The study includes ozone data from areas with limited previous data, notably tropical South America, central Africa and tropical northern Australia. Evaluating UKESM1 against observations beginning in 1987 onwards, we show that UKESM1 is able to capture changes in surface ozone concentration at different temporal resolutions, albeit with a systematic high bias of 18.1 nmol mol−1 on average. We use the diurnal ozone range (DOR) as a metric for evaluation and find that UKESM1 captures the observed DOR (mean bias of 2.7 nmol mol−1 and RMSE of 7.1 nmol mol−1) and the trend in DOR with location and season. Results from this study reveal that hourly ozone concentrations from UKESM1 require bias correction before use for impact assessments based on human and ecosystem health. Indeed, hourly surface ozone data have been crucial to this study, and we encourage other modelling groups to include hourly surface ozone output as a default.

Abstract Physical activity (PA) improves dyspnoea, psychological wellbeing and quality of life (QoL) for people with COPD reducing their risk of exacerbation. However, engagement in PA is low especially amongst those with anxiety and depression, and PA programmes are limited in countries with limited resources such as Brazil. We explored perceptions of 21 people with COPD about the impact of their disease on taking part in community-based PA programmes in Sao Paulo, Brazil through semi-structured telephone interviews from October 2020 to April 2021. Discussions were audio-recorded, transcribed, and analysed using the Framework method. Five themes were identified: Knowledge about COPD and its management; Self-perception of life with COPD; Knowledge and experiences of depression and anxiety; Opinions on PA and repercussions of COVID-19. PA was considered to be important in bringing physical and mental health benefits but there were barriers in accessibility of formal PR programmes and therefore local community PA programmes were considered to be important. People with mental health conditions tended to view PA more negatively. COVID-19 had reduced PA opportunities, access to COPD treatment and social interaction, and was associated with more exacerbations and emotional suffering. In general, this study showed an urgent need to improve knowledge about COPD and its risk factors and management among both patients, the public and primary healthcare professionals. We provide important content for the formulation of public policies for the implementation of specific activity programmes for people with COPD in community spaces using local resources and intersectoral partnerships.

Abstract Background Many countries have introduced school food standards to improve the dietary intakes of school-aged children. England has school food standards (SFS) legislation in place but little is known about how well secondary schools comply with this. We aimed to assess compliance with the SFS legislation in English secondary schools and explore the impact of the SFS on pupils’ nutritional intake. Methods We conducted a cross-sectional study with English secondary schools from 2019 to 2022. We compared SFS compliance and pupil nutritional intake in schools mandated or not mandated to comply with the SFS legislation, and explored the association between school compliance and pupil nutritional intake. We assessed the percentage of SFS (%SFS) complied with by reviewing school food menus and observing food served in school canteens. We assessed pupil nutritional intake using a 24-hour dietary recall measure (Intake24) and estimated intakes of free sugar (primary outcome) and other nutrients/foods. We used adjusted multilevel models to compare pupil intakes in the SFS-mandated and SFS-non-mandated schools, and to explore the association between school SFS compliance and pupil intakes. Results 36 schools (23 not mandated and 13 mandated to comply with the SFS) and 2,273 pupils participated. The median %SFS complied with was 63.9% (interquartile range 60.0–70.0%). This was similar for SFS-non-mandated (64.5%) and SFS-mandated schools (63.3%). Compliance was highest for standards applying to lunchtime (median = 81.3%) and lowest for those applying across the whole school day (median = 41.7%). It was also lower for standards restricting high fat, sugar and energy-dense items (median = 26.1%) than for standards aiming to increase dietary variety (median = 92.3%). Pupils from SFS-mandated schools had a lower mean lunchtime intake of free sugar (g) (adjusted mean difference: -2.78g; 95% CI: -4.66g to -0.90g). There were few significant associations between %SFS complied with and pupil nutritional intake. Conclusions English secondary schools do not fully comply with SFS legislation regardless of whether they are mandated to comply. Schools and caterers may require monitoring and support to fully comply. There is little evidence that SFS compliance is associated with better pupil nutritional intake. Food environments outside of school also need to be considered. Study registration ISRCTN68757496 (17-10-2019).

Abstract Background The majority of junior doctors in the UK do not proceed directly into specialty training after completing mandatory foundation training but instead take a year out of training. A common post undertaken during a year out of training is a clinical teaching fellow (CTF) role which is used to provide undergraduate medical student teaching. There is only a small amount of literature available regarding CTF posts, and very little of this explores experiences or reasons for taking up such as post. An understanding of the reasons why doctors are choosing to work as CTFs and what their experiences are in post will contribute to how the role is further developed and utilised within the NHS. This study aimed to explore the experiences of CTFs employed in the West Midlands at NHS hospital Trusts. Methods CTFs working in Trusts in the West Midlands region registered as students on the Education for Healthcare Professionals Post Graduate Certificate course at the University of Birmingham in August 2019 and 2020 who were enrolled in a longitudinal study were invited to take part in an individual interview asking about their experiences as CTFs. Results Nine CTFs participated in an interview. Five main themes were identified which related to their experiences in post and plans for future careers. Participants reported choosing to undertake a CTF role due to wanting a break from clinical work and having previously enjoyed delivering teaching. Positive experiences in post included lifestyle related benefits and self-development opportunities. Challenges identified with the role included the impact of COVID-19 and volume of students. Conclusion This is the first study to use interview methodology to explore experiences of CTFs, and has provided a valuable insight into the experiences of those in post in the West Midlands region. Understanding why doctors chose this job and what their experiences are could help to further develop and refine the role. To guarantee demands for teaching staff are met those employing CTFs should be aware of reasons why doctors apply for the post and ensure the post remains a desirable option.

Abstract Microbial carbon use efficiency (CUE) affects the fate and storage of carbon in terrestrial ecosystems, but its global importance remains uncertain. Accurately modeling and predicting CUE on a global scale is challenging due to inconsistencies in measurement techniques and the complex interactions of climatic, edaphic, and biological factors across scales. The link between microbial CUE and soil organic carbon relies on the stabilization of microbial necromass within soil aggregates or its association with minerals, necessitating an integration of microbial and stabilization processes in modeling approaches. In this perspective, we propose a comprehensive framework that integrates diverse data sources, ranging from genomic information to traditional soil carbon assessments, to refine carbon cycle models by incorporating variations in CUE, thereby enhancing our understanding of the microbial contribution to carbon cycling.

Kate Jolly,1 Saimma Majothi,1 Alice J Sitch,1 Nicola R Heneghan,2 Richard D Riley,3 David J Moore,1 Elizabeth J Bates,1 Alice M Turner,4 Susan E Bayliss,1 Malcolm J Price,1 Sally J Singh,5 Peymane Adab,1 David A Fitzmaurice,1 Rachel E Jordan11Institute of Applied Health Research, 2School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Edgbaston, Birmingham, 3Research Institute of Primary Care and Health Sciences, Keele University, Keele, Staffordshire, 4Institute of Inflammation and Ageing, University of Birmingham, Birmingham, 5Centre for Exercise and Rehabilitation Science, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, UKPurpose: This systematic review aimed to identify the most effective components of interventions to facilitate self-management of health care behaviors for patients with COPD. PROSPERO registration number CRD42011001588.Methods: We used standard review methods with a systematic search to May 2012 for randomized controlled trials of self-management interventions reporting hospital admissions or health-related quality of life (HRQoL). Mean differences (MD), hazard ratios, and 95% confidence intervals (CIs) were calculated and pooled using random-effects meta-analyses. Effects among different subgroups of interventions were explored including single/multiple components and multicomponent interventions with/without exercise.Results: One hundred and seventy-three randomized controlled trials were identified. Self-management interventions had a minimal effect on hospital admission rates. Multicomponent interventions improved HRQoL (studies with follow-up >6 months St George’s Respiratory Questionnaire (MD 2.40, 95% CI 0.75–4.04, I2 57.9). Exercise was an effective individual component (St George’s Respiratory Questionnaire at 3 months MD 4.87, 95% CI 3.96–5.79, I2 0%).Conclusion: While many self-management interventions increased HRQoL, little effect was seen on hospital admissions. More trials should report admissions and follow-up participants beyond the end of the intervention. Keywords: COPD, self-management, systematic review, meta-analysis

Surface ozone (O3) is the primary air pollutant threatening global vegetation. It typically reduces the photosynthetic rate and stomatal conductance, leading to changes in carbon, water, and energy cycles; vegetation structure and composition; and climate. Several parameterization schemes have been developed to integrate the photosynthetic and stomatal responses to O3 exposure in regional and global process-based models to simulate time- and space-varying O3 plant damage and its cascading dynamic influence. However, these schemes are calibrated based on limited observations and often fail to reproduce the response relationships in observations, impeding accurate assessments of the role of O3 plant damage in the Earth system. This study proposes a new parameterization scheme to utilize the extensive observations from O3 fumigation experiments to inform large-scale modeling. It is built on 4210 paired data points of photosynthetic and stomatal responses compiled from the peer-reviewed literature, more than 6 times larger than those employed in earlier schemes. Functions of phytotoxic O3 dose (POD) are found to accurately reproduce the statistically significant linear or nonlinear relationships observed between POD and either relative leaf photosynthetic rate or relative stomatal conductance for needleleaf trees, broadleaf trees, shrubs, grasses, and crops. These eliminate the practice in earlier schemes of setting response functions as constants and applying the response function from one vegetation type to another. It outperforms the old scheme in the Community Land Model (CLM), which skillfully reproduces the observed response for crop photosynthetic rate only. The nonlinear response functions we developed depict decreasing plant sensitivity with increases in POD, enabling models to implicitly capture the variability in plant ozone tolerance and the shift among plant species for both intra- and inter-PFTs (plant functional types) within a vegetation type observed in the real world. Then, the new scheme is incorporated into the Community Earth System Model version 2.2 (CESM2.2), specifically its land component CLM5, to quantify the global impacts of present-day O3 plant damage by comparing the simulations with and without O3 plant damage. Results show that O3 exposure reduces the global leaf photosynthetic rate by 8.5 % and stomatal conductance by 7.4 %, around half the estimates using the old scheme. Furthermore, the new scheme improves global gross primary productivity (GPP) simulations, decreasing RMSE by 11.1 % relative to simulations without O3 plant damage and by 11.7 % compared to the old scheme. These results underscore the importance of including O3 plant damage in large-scale process-based models and the effectiveness of the new scheme in assessing and projecting globally the role of O3 plant damage in the Earth system.

Climate change has been partially mitigated by an increasing net land carbon sink in the terrestrial biosphere; understanding the processes that drive this sink is thus essential for protecting, managing and projecting this important ecosystem service. In this Review, we examine evidence for an enhanced land carbon sink and attribute the observed response to drivers and processes. This sink has doubled from 1.2 ± 0.5 PgC yr−1 in the 1960s to 3.1 ± 0.6 PgC yr−1 in the 2010s. This trend results largely from carbon dioxide fertilization increasing photosynthesis (driving an increase in the annual land carbon sink of >2 PgC globally since 1900), mainly in tropical forest regions, and elevated temperatures reducing cold limitation, mainly at higher latitudes. Continued long-term land carbon sequestration is possible through the end of this century under multiple emissions scenarios, especially if nature-based climate solutions and appropriate ecosystem management are used. A new generation of globally distributed field experiments is needed to improve understanding of future carbon sink potential by measuring belowground carbon release, the response to carbon dioxide enrichment, and long-term shifts in carbon allocation and turnover.

Communication is a core component of a clinician’s role; however, when clinicians conduct research, communicating the emerging findings and recommendations to different types of stakeholders can be unfamiliar territory. Communicating research to advocate for change can be even more challenging. Clinician researchers seeking to be agents for change need to conceive and craft specific, evidence-based messages and communicate these effectively to different stakeholders to negotiate action. As part of a global health research program, we developed and tested a novel game-based model to strengthen the communication skills of clinician researchers, from 4 countries, for improving services for chronic obstructive pulmonary disease. This model focused on communication with 3 key stakeholder groups for knowledge translation: Patients/carers, healthcare providers and policy makers/healthcare managers. Delivered through a series of facilitated, online meetings, this model consisted of 2 parts: developing and rehearsing advocacy messages with coaching support, and then testing them with a panel of 3 representative stakeholders, and an audience of fellow researchers. All the country teams reported increased confidence in crafting advocacy messages for specific stakeholders and have applied lessons learned from the model. Delivering this model within a global health research program requires mentoring, time, commitment, resources and translation support to address language barriers. It offers an exemplar to build the communication skills of clinician and non-clinician researchers so that they can go beyond dissemination toward translation of evidence into policy and practice.

Identifying the thresholds of drought that, if crossed, suppress vegetation functioning is vital for accurate quantification of how land ecosystems respond to climate variability and change. We present a globally applicable framework to identify drought thresholds for vegetation responses to different levels of known soil-moisture deficits using four remotely sensed vegetation proxies spanning 2001-2018. The thresholds identified represent critical inflection points for changing vegetation responses from highly resistant to highly vulnerable in response to drought stress, and as a warning signal for substantial vegetation impacts. Drought thresholds varied geographically, with much lower percentiles of soil-moisture anomalies in vegetated areas covered by more forests, corresponding to a comparably stronger capacity to mitigate soil water deficit stress in forested ecosystems. Generally, those lower thresholds are detected in more humid climates. State-of-the-art land models, however, overestimated thresholds of soil moisture (i.e. overestimating drought impacts), especially in more humid areas with higher forest covers and arid areas with few forest covers. Based on climate model projections, we predict that the risk of vegetation damage will increase by the end of the twenty-first century in some hotspots like East Asia, Europe, Amazon, southern Australia and eastern and southern Africa. Our data-based results will inform projections on future drought impacts on terrestrial ecosystems and provide an effective tool for drought management.

Abstract Forest carbon sequestration capacity in China remains uncertain due to underrepresented tree demographic dynamics and overlooked of harvest impacts. In this study, we employ a process-based biogeochemical model to make projections by using national forest inventories, covering approximately 415,000 permanent plots, revealing an expansion in biomass carbon stock by 13.6 ± 1.5 Pg C from 2020 to 2100, with additional sink through augmentation of wood product pool (0.6-2.0 Pg C) and spatiotemporal optimization of forest management (2.3 ± 0.03 Pg C). We find that statistical model might cause large bias in long-term projection due to underrepresentation or neglect of wood harvest and forest demographic changes. Remarkably, disregarding the repercussions of harvesting on forest age can result in a premature shift in the timing of the carbon sink peak by 1–3 decades. Our findings emphasize the pressing necessity for the swift implementation of optimal forest management strategies for carbon sequestration enhancement.

Abstract The northern terrestrial biomes are being remarkably altered by climate change. Higher springtime temperature induces the earlier greening of vegetation, which may further influence ecosystem functions during the subsequent season. However, the response of summer net ecosystem productivity to spring vegetation greenness and phenology changes has not yet been quantified. To understand the impact of such phenological changes on terrestrial carbon sink of the following season, here we integrate remotely-sensed vegetation data and model simulations of carbon flux with an explainable machine learning approach. We find that the lagged effects of widespread earlier spring greening are increasing the summer ecosystem carbon sink across the northern vegetated areas (30° to 90°N) from 1982 to 2015. In particular, response disparities exist in non-agricultural biomes, and the vegetation with moderate tree coverage is more sensitive to earlier spring greening. Furthermore, modest tree restoration can strengthen the beneficial effects of earlier spring greening. This study improves our understanding of interseasonal vegetation-climate-carbon coupling that drives the key ecological feedback within climate change projections.

Abstract Background Many UK junior doctors are now taking a year out of the traditional training pathway, usually before specialty training, and some choose to work as a clinical teaching fellow (CTF). CTFs primarily have responsibility for delivering hospital-based teaching to undergraduate medical students. Only a very small amount of literature is available regarding CTF posts, none of which has explored why doctors choose to undertake the role and their expectations of the job. This study aimed to explore the expectations and experiences of CTFs employed at NHS hospital Trusts in the West Midlands. Methods CTFs working in Trusts in the West Midlands region registered as students on the Education for Healthcare Professionals Post Graduate Certificate course at the University of Birmingham in August 2019 took part in a survey and a focus group. Results Twenty-eight CTFs participated in the survey and ten participated in the focus group. In the survey, participants reported choosing a CTF role due to an interest in teaching, wanting time out of training, and being unsure of which specialty to choose. Expectations for the year in post were directly related to reasons for choosing the role with participants expecting to develop teaching skills, and have a break from usual clinical work and rotations. The focus group identified five main themes relating to experiences starting their job, time pressures and challenges faced in post, how CTF jobs differed between Trusts, and future career plans. Broadly, participants reported enjoying their year in a post at a mid-year point but identified particular challenges such as difficulties in starting the role and facing time pressures in their day-to-day work. Conclusion This study has provided a valuable insight into the CTF role and why doctors choose a CTF post and some of the challenges experienced, adding to the sparse amount of literature. Understanding post holders’ experiences may contribute to optimisation of the role. Those employing CTFs should consider ensuring a formal handover process is in place between outgoing and incoming CTFs, having a lead person at their Trust responsible for evaluating changes suggested by CTFs, and the balance of contractual duties and personal development time.

Background Estimation of glomerular filtration rate using equations based on creatinine is widely used to manage chronic kidney disease. In the UK, the Chronic Kidney Disease Epidemiology Collaboration creatinine equation is recommended. Other published equations using cystatin C, an alternative marker of kidney function, have not gained widespread clinical acceptance. Given higher cost of cystatin C, its clinical utility should be validated before widespread introduction into the NHS. Objectives Primary objectives were to: (1) compare accuracy of glomerular filtration rate equations at baseline and longitudinally in people with stage 3 chronic kidney disease, and test whether accuracy is affected by ethnicity, diabetes, albuminuria and other characteristics; (2) establish the reference change value for significant glomerular filtration rate changes; (3) model disease progression; and (4) explore comparative cost-effectiveness of kidney disease monitoring strategies. Design A longitudinal, prospective study was designed to: (1) assess accuracy of glomerular filtration rate equations at baseline (n = 1167) and their ability to detect change over 3 years (n = 875); (2) model disease progression predictors in 278 individuals who received additional measurements; (3) quantify glomerular filtration rate variability components (n = 20); and (4) develop a measurement model analysis to compare different monitoring strategy costs (n = 875). Setting Primary, secondary and tertiary care. Participants Adults (≥ 18 years) with stage 3 chronic kidney disease. Interventions Estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations. Main outcome measures Measured glomerular filtration rate was the reference against which estimating equations were compared with accuracy being expressed as P30 (percentage of values within 30% of reference) and progression (variously defined) studied as sensitivity/specificity. A regression model of disease progression was developed and differences for risk factors estimated. Biological variation components were measured and the reference change value calculated. Comparative costs of monitoring with different estimating equations modelled over 10 years were calculated. Results Accuracy (P30) of all equations was ≥ 89.5%: the combined creatinine–cystatin equation (94.9%) was superior (p 5%/year difference between mGFR and eGFR. Ability of equations to detect change was studied based on whether or not eGFR detected overall change, or decline only, in mGFR over 3 years against threshold changes variously defined as (1) > 10 ml/minute/1.73 m2; (2) > reference change value (RCV) (a > 21.5% increase or a > 17.7% decrease); (3) > 25% change; and (4) > 25% change and a change in disease stage. Sensitivity and specificity of eGFRs to identify progressive disease were evaluated. Estimated GFRs, in addition to urinary ACR, were also tested as predictors of progression and mortality. In the substudy of disease progression the change in mGFR, and the difference between mGFRs and eGFRs (bias), assessed every 12 months, were modelled over time using a longitudinal linear random coefficients regression model, to estimate average and variability in disease progression and bias. A model of disease progression based on mGFR was developed and differences in progression for risk factors estimated. In the biological variation substudy, analytical (CVA) and individual (CVI) components of variation were calculated and used to derive the RCV for significant changes in serial results for both mGFR and eGFR. Results from the main study informed a measurement model analysis. The trajectory of participants mGFR and eGFR over 10 years was used to estimate the proportion meeting the National Institute for Health and Care Excellence (NICE) definition of accelerated progression or of progression to CKD stage G4, assuming an annual testing schedule, and the number of participants expected to be incorrectly managed at each of the evaluated monitoring time points using different estimating equations. Based on the findings, the comparative costs of monitoring with GFR-estimating equations were calculated. Sample size Main study. Complete baseline data n = 1167. Three-year follow-up GFR data n = 875. Disease progression substudy. n = 278. Biological variation substudy. n = 20. Results All estimates of GFR relating to the primary study objectives were negatively biased compared to mGFR. There was no difference in median bias (ml/minute/1.73 m2) against mGFR between the MDRD (−3.7), CKD-EPIcreatinine (−2.8), CKD-EPIcystatin (−4.1) and CKD-EPIcreatinine-cystatin (−3.9) equations. Accuracy (P30) of the CKD-EPIcystatin equation (89.5%) did not differ from that of the MDRD (89.5%) and CKD-EPIcreatinine (90.2%) equations: accuracy of the CKD-EPIcreatinine-cystatin equation (94.9%) was superior (p 70% concordance. The CKD-EPIcreatinine-cystatin equation had better concordance than the other three primary study equations (p 83% in all cases), sensitivity for detecting change was < 63% in all cases. There was no clear difference in sensitivity or specificity between the four main study equations. For all equations and all thresholds, there was no clear evidence of improved performance of cystatin-containing equations compared to their matched creatinine-only equation. In the substudy of disease progression, modelling data showed a strong association between albuminuria status and rate of progression in mGFR and CKD-EPIcreatinine eGFR, with those with albuminuria having faster progression (steeper decline). Higher baseline mGFR values were associated with faster progression rate for mGFR. African-Caribbean ethnicity increased (slower decline) and South Asian ethnicity decreased (faster decline) the estimate of progression slope for mGFR and CKD-EPIcreatinine GFR. However, recruitment of ethnic minority participants in particular to the substudy fell short of target, limiting the strength of any conclusions. Within-subject biological variation of mGFR was 6.7%, with similar, although in some cases significantly lower, biological variation of eGFR (5.0, 5.3, 5.3 and 5.0% for MDRD, CKD-EPIcreatinine, CKD-EPIcystatin and CKD-EPIcreatinine-cystatin equations, respectively). Derived RCVs (%, positive/negative) were 21.5/−17.7 (mGFR), 15.1/−13.1 (MDRD), 15.9/−13.7 (CKD-EPIcreatinine), 15.9/−13.8 (CKD-EPIcystatin) and 15.1/−13.1 (CKD-EPIcreatinine-cystatin). We observed 62 deaths during the 3-year follow-up period. The study was not powered for hard end points. However, in agreement with earlier studies, regression models including each GFR-estimating equation separately demonstrated mortality was associated with lower eGFR, increasing age and male gender. An association with categorical albuminuria was not observed. There was no evidence of superiority of CKD-EPI equations, including the cystatin C-containing equations, as predictors of death compared to the MDRD equation. A measurement model analysis found no evidence to suggest that any of the estimating equations were superior for identifying CKD progression based on NICE-defined clinical end points. The average incremental per patient costs (compared to MDRD) of monitoring over a 10-year period using the cystatin C-based equations were estimated (CKD-EPIcystatin £42.20; CKD-EPIcreatinine-cystatin £43.32). Conclusions Most GFR equations achieved acceptable accuracy as judged by P30. There was little difference between the equations in accuracy, with evidence of superior accuracy for the CKD-EPIcreatinine-cystatin equation. Across several important characteristics (age, gender, diabetes, albuminuria, BMI, GFR level) we found no difference in accuracy of GFR-estimating equations. In relation to GFR estimation in African-Caribbean individuals, there was evidence to suggest caution should be exercised before advocating simple removal of the black race factor from the original CKD-EPI equations. In the longitudinal study, the CKD-EPIcreatinine-cystatin displayed slightly better concordance with mGFR than the other main study equations when tracking patients, but all study equations underestimated the mGFR decline. The sensitivity of GFR equations to detect clinically relevant threshold changes in mGFR, either overall or when considering decline in GFR only, was ≤ 63% for all equations. This is of concern given that such thresholds, including the NICE definition of accelerated progression and the change recognised as being true as determined by biological variation (RCV), were studied. Overall, data comparing the accuracy of different GFR-estimating equations demonstrated no notable benefit of using a cystatin C-containing equation in detecting GFR change. The measurement model underpinning the health economic analysis focused on the comparative accuracy of the estimating equations to detect accelerated progression. The analysis estimated accuracy over a longer trajectory than the main study and factored in measurement error, but found no clear benefit of using a cystatin C-based estimating equation. There was therefore no evidence to suggest that adding cystatin C measurement to current GFR monitoring protocols would be cost-effective. The disease progression modelling of the substudy data noted faster progression associated with higher baseline GFR and albuminuria; the latter consistent with other studies. Any conclusions relating to the influence of ethnicity were tempered by poor recruitment of ethnic minority individuals. The biological variability data have implications for monitoring of patients with CKD and clinical ability to understand CKD progression, both in clinical practice and research. The information presented provides an evidence base allowing clinicians to have meaningful discussions with their patients about the implications of changes in their GFR results. Inclusion of cystatin C in GFR-estimating equations was associated with marginal improvements in accuracy, but no clear advantages in terms of detecting GFR change over time. Problems of standardisation of cystatin C assays remain, despite the introduction of an international standard. The use of cystatin C increases the economic cost of CKD monitoring with little apparent gain. These data do not support the use of cystatin C for the routine monitoring of GFR in people with stage 3 CKD. Further research is warranted to investigate specific patient groups that may benefit from cystatin C use. Trial registration This trial is registered as ISRCTN42955626 www.controlled-trials.com/ISRCTN42955626 (accessed 26 July 2023). Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/103/01) and is published in full in Health Technology Assessment; Vol. 28, No. 35. See the NIHR Funding and Awards website for further award information.

Abstract Plants with the C4 photosynthesis pathway typically respond to climate change differently from more common C3-type plants, due to their distinct anatomical and biochemical characteristics. These different responses are expected to drive changes in global C4 and C3 vegetation distributions. However, current C4 vegetation distribution models may not predict this response as they do not capture multiple interacting factors and often lack observational constraints. Here, we used global observations of plant photosynthetic pathways, satellite remote sensing, and photosynthetic optimality theory to produce an observation-constrained global map of C4 vegetation. We find that global C4 vegetation coverage decreased from 17.7% to 17.1% of the land surface during 2001 to 2019. This was the net result of a reduction in C4 natural grass cover due to elevated CO2 favoring C3-type photosynthesis, and an increase in C4 crop cover, mainly from corn (maize) expansion. Using an emergent constraint approach, we estimated that C4 vegetation contributed 19.5% of global photosynthetic carbon assimilation, a value within the range of previous estimates (18–23%) but higher than the ensemble mean of dynamic global vegetation models (14 ± 13%; mean ± one standard deviation). Our study sheds insight on the critical and underappreciated role of C4 plants in the contemporary global carbon cycle.

Abstract The Amazon is the largest continuous tropical forest in the world and plays a key role in the global carbon cycle. Human-induced disturbances and climate change have impacted the Amazon carbon balance. Here we conduct a comprehensive synthesis of existing state-of-the-art estimates of the contemporary land carbon fluxes in the Amazon using a set of bottom-up methods (i.e., dynamic vegetation models and bookkeeping models) and a top-down inversion (atmospheric inversion model) over the Brazilian Amazon and the whole Biogeographical Amazon domain. Over the whole biogeographical Amazon region bottom-up methodologies suggest a small average carbon sink over 2010-2020, in contrast to a small carbon source simulated by top-down inversion (2010-2018). However, these estimates are not significantly different from one another when accounting for their large individual uncertainties, highlighting remaining knowledge gaps, and the urgent need to reduce such uncertainties. Nevertheless, both methodologies agreed that the Brazilian Amazon has been a net carbon source during recent climate extremes and that the south-eastern Amazon was a net land carbon source over the whole study period (2010-2020). Overall, our results point to increasing human-induced disturbances (deforestation and forest degradation by wildfires) and reduction in the old-growth forest sink during drought.

The reduction of CO2 emissions and the enhancement of CO2 removals related to land use are considered essential for future pathways towards net-zero emissions and mitigating climate change. With the growing pressure under global climate treaties, country-level land-use CO2 flux data are becoming increasingly important. So far, country-level estimates are mainly available through official country reports, such as the greenhouse gas inventories reported to the United Nations Framework Convention on Climate Change (UNFCCC). Recently, different modelling approaches, namely dynamic global vegetation models (DGVMs) and bookkeeping models, have moved to higher spatial resolutions, which makes it possible to obtain model-based country-level estimates that are globally consistent in their methodology. To progress towards a largely independent assessment of country reports using models, we analyse the robustness of country-level CO2 flux estimates from different modelling approaches in the period 1950–2021 and compare them with estimates from country reports. Our results highlight the general ability of modelling approaches to estimate land-use CO2 fluxes at the country level and at higher spatial resolution. Modelled land-use CO2 flux estimates generally agree well, but the investigation of multiple DGVMs and bookkeeping models reveals that the robustness of their estimates strongly varies across countries, and substantial uncertainties remain, even for top emitters. Similarly, modelled land-use CO2 flux estimates and country-report-based estimates agree reasonably well in many countries once their differing definitions are accounted for, although differences remain in some other countries. A separate analysis of CO2 emissions and removals from land use using bookkeeping models also shows that historical peaks in net fluxes stem from emission peaks in most countries, whereas the long-term trends are more connected to removal dynamics. The ratio of the net flux to the sum of CO2 emissions and removals from land use (the net-to-gross flux ratio) underlines the spatio-temporal heterogeneity in the drivers of net land-use CO2 flux trends. In many tropical regions, net-to-gross flux ratios of about 50 % are due to much larger emissions than removals; in many temperate countries, ratios close to zero show that emissions and removals largely offset each other. Considering only the net flux thus potentially masks large emissions and removals and the different timescales upon which they act, particularly if averaged over countries or larger regions, highlighting the need for future studies to focus more on the gross fluxes. Data from this study are openly available via the Zenodo portal at https://doi.org/10.5281/zenodo.8144174 (Obermeier et al., 2023).

Abstract Background Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned. Main body Each country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice. Conclusion Stakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.

Introduction Childbirth-related perineal trauma (CRPT) is the most common complication of childbirth affecting 80% of women overall after vaginal birth. There remains a lack of comprehensive evidence relating to the prevalence of subsequent health problems. Current evidence is related to short-term outcomes, for example, pain, but there is less known about longer-term outcomes such as infection, wound dehiscence, pelvic floor function and psychological outcomes. This is a protocol for a cohort study assessing outcomes of women after CRPT.Methods and analysis A multicentre, prospective UK cohort study aiming to include 1000 women. All women who have sustained CRPT will be eligible for inclusion and will be followed-up for 12 months after childbirth. The primary outcome will be perineal infection at 6 weeks post-birth. Secondary outcomes will include antibiotic use for perineal infection, wound breakdown, use of analgesia, the requirement for admission or surgical intervention, urinary and faecal incontinence, anxiety and depressive symptoms, sexual function and impact on daily activities. Outcomes will be measured at 6 weeks, 6 months and 12 months post partum, with some outcomes being measured at all time points and others at selected most appropriate time points only. Outcome data will be obtained from a review of clinical notes and from patient questionnaires. Simple descriptive statistics will be used to summarise characteristics and outcomes, with categorical variables expressed as percentages and continuous variables as mean averages, alongside the corresponding standard deviatons.Ethics and dissemination Ethical approval has been granted by the Research Ethics Council with reference 23/WA/0169. Data collected from the Childbirth Acquired Perineal Trauma (CHAPTER) cohort study will highlight the prevalence and type of complications after CRPT and which women are more at risk. After the conclusion of this study, findings will be used to work with governmental organisations and Royal Colleges to target resources and ultimately improve care.