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The global secondary organic aerosol (SOA) budget is highly uncertain, with global annual SOA production rates, estimated from global models, ranging over an order of magnitude and simulated SOA concentrations underestimated compared to observations. In this study, we use a global composition-climate model (UKCA) with interactive chemistry and aerosol microphysics to provide an in-depth analysis of the impact of each VOC source on the global SOA budget and its seasonality. We further quantify the role of each source on SOA spatial distributions, and evaluate simulated seasonal SOA concentrations against a comprehensive set of observations. The annual global SOA production rates from monoterpene, isoprene, biomass burning, and anthropogenic precursor sources is 19.9, 19.6, 9.5, and 24.6 Tg (SOA) a−1, respectively. When all sources are included, the SOA production rate from all sources is 73.6 Tg (SOA) a−1, which lies within the range of estimates from previous modelling studies. SOA production rates and SOA burdens from biogenic and biomass burning SOA sources peak during Northern Hemisphere (NH) summer. In contrast, the anthropogenic SOA production rate is fairly constant all year round. However, the global anthropogenic SOA burden does have a seasonal cycle which is lowest during NH summer, which is probably due to enhanced wet removal. Inclusion of the new SOA sources also accelerates the ageing by condensation of primary organic aerosol (POA), making it more hydrophilic, leading to a reduction in the POA lifetime. With monoterpene as the only source of SOA, simulated SOA and total organic aerosol (OA) concentrations are underestimated by the model when compared to surface and aircraft measurements. Model agreement with observations improves with all new sources added, primarily due to the inclusion of the anthropogenic source of SOA, although a negative bias remains. A further sensitivity simulation was performed with an increased anthropogenic SOA reaction yield, corresponding to an annual global SOA production rate of 70.0 Tg (SOA) a−1. Whilst simulated SOA concentrations improved relative to observations, they were still underestimated in urban environments and overestimated further downwind and in remote environments. In contrast, the inclusion of SOA from isoprene and biomass burning did not improve model–observations biases substantially except at one out of two tropical locations. However, these findings may reflect the very limited availability of observations to evaluate the model, which are primarily located in the NH mid-latitudes where anthropogenic emissions are high. Our results highlight that, within the current uncertainty limits in SOA sources and reaction yields, over the NH mid-latitudes, a large anthropogenic SOA source results in good agreement with observations. However, more observations are needed to establish the importance of biomass burning and biogenic sources of SOA in model agreement with observations.

Indigenous Australians harbour rich and unique genomic diversity. However, Aboriginal and Torres Strait Islander ancestries are historically under-represented in genomics research and almost completely missing from reference datasets 1 – 3 . Addressing this representation gap is critical, both to advance our understanding of global human genomic diversity and as a prerequisite for ensuring equitable outcomes in genomic medicine. Here we apply population-scale whole-genome long-read sequencing 4 to profile genomic structural variation across four remote Indigenous communities. We uncover an abundance of large insertion–deletion variants (20–49 bp; n  = 136,797), structural variants (50  b–50 kb; n  = 159,912) and regions of variable copy number (>50 kb; n  = 156). The majority of variants are composed of tandem repeat or interspersed mobile element sequences (up to 90%) and have not been previously annotated (up to 62%). A large fraction of structural variants appear to be exclusive to Indigenous Australians (12% lower-bound estimate) and most of these are found in only a single community, underscoring the need for broad and deep sampling to achieve a comprehensive catalogue of genomic structural variation across the Australian continent. Finally, we explore short tandem repeats throughout the genome to characterize allelic diversity at 50 known disease loci 5 , uncover hundreds of novel repeat expansion sites within protein-coding genes, and identify unique patterns of diversity and constraint among short tandem repeat sequences. Our study sheds new light on the dimensions and dynamics of genomic structural variation within and beyond Australia. Population-scale whole-genome sequencing across four remote Indigenous Australian communities reveals a large fraction of structural variants that are unique to these populations, emphasizing the genetic distinctiveness of and diversity among Indigenous Australians.

In Australia, opportunistic screening (occurring as skin checks) for the early detection of melanoma is common, and overdiagnosis is a recognised concern. Risk-tailored cancer screening is an approach to cancer control that aims to provide personalised screening tailored to individual risk. This study aimed to explore the views of key informants in Australia on the acceptability and appropriateness of risk-tailored organised screening for melanoma, and to identify barriers, facilitators and strategies to inform potential future implementation. Acceptability and appropriateness are crucial, as successful implementation will require a change of practice for clinicians and consumers. This was a qualitative study using semi-structured interviews. Key informants were purposively selected to ensure expertise in melanoma early detection and screening, prioritising senior or executive perspectives. Consumers were expert representatives. Data were analysed deductively using the Tailored Implementation for Chronic Diseases (TICD) checklist. Thirty-six participants were interviewed (10 policy makers; 9 consumers; 10 health professionals; 7 researchers). Key informants perceived risk-tailored screening for melanoma to be acceptable and appropriate in principle. Barriers to implementation included lack of trial data, reluctance for low-risk groups to not screen, variable skill level in general practice, differing views on who to conduct screening tests, confusing public health messaging, and competing health costs. Key facilitators included the perceived opportunity to improve health equity and the potential cost-effectiveness of a risk-tailored screening approach. A range of implementation strategies were identified including strengthening the evidence for cost-effectiveness, engaging stakeholders, developing pathways for people at low risk, evaluating different risk assessment criteria and screening delivery models and targeted public messaging. Key informants were supportive in principle of risk-tailored melanoma screening, highlighting important next steps. Considerations around risk assessment, policy and modelling the costs of current verses future approaches will help inform possible future implementation of risk-tailored population screening for melanoma.

A previous model intercomparison of the Tambora aerosol cloud has highlighted substantial differences among simulated volcanic aerosol properties in the pre-industrial stratosphere and has led to questions about the applicability of global aerosol models for large-magnitude explosive eruptions prior to the observational period. Here, we compare the evolution of the stratospheric aerosol cloud following the well-observed June 1991 Mt. Pinatubo eruption simulated with six interactive stratospheric aerosol microphysics models to a range of observational data sets.Our primary focus is on the uncertainties regarding initial SO2 emission following the Pinatubo eruption, as prescribed in the Historical Eruptions SO2 Emission Assessment experiments (HErSEA), in the framework of the Interactive Stratospheric Aerosol Model Intercomparison Project (ISA-MIP). Six global models with interactive aerosol microphysics took part in this study: ECHAM6-SALSA, EMAC, ECHAM5-HAM, SOCOL-AERv2, ULAQ-CCM, and UM-UKCA. Model simulations are performed by varying the SO2 injection amount (ranging between 5 and 10 Tg S) and the altitude of injection (between 18–25 km).The comparisons show that all models consistently demonstrate faster reduction from the peak in sulfate mass burden in the tropical stratosphere. Most models also show a stronger transport towards the extratropics in the Northern Hemisphere, at the expense of the observed tropical confinement, suggesting a much weaker subtropical barrier in all the models, which results in a shorter e-folding time compared to the observations. Furthermore, simulations in which more than 5 Tg S in the form of SO2 is injected show an initial overestimation of the sulfate burden in the tropics and, in some models, in the Northern Hemisphere and a large surface area density a few months after the eruption compared to the values measured in the tropics and the in situ measurements over Laramie. This draws attention to the importance of including processes such as the ash injection for the removal of the initial SO2 and aerosol lofting through local heating.

Melanoma of the skin is a common cancer only in Europeans, whereas it arises in internal body surfaces (mucosal sites) and on the hands and feet (acral sites) in people throughout the world. Here we report analysis of whole-genome sequences from cutaneous, acral and mucosal subtypes of melanoma. The heavily mutated landscape of coding and non-coding mutations in cutaneous melanoma resolved novel signatures of mutagenesis attributable to ultraviolet radiation. However, acral and mucosal melanomas were dominated by structural changes and mutation signatures of unknown aetiology, not previously identified in melanoma. The number of genes affected by recurrent mutations disrupting non-coding sequences was similar to that affected by recurrent mutations to coding sequences. Significantly mutated genes included BRAF , CDKN2A , NRAS and TP53 in cutaneous melanoma, BRAF , NRAS and NF1 in acral melanoma and SF3B1 in mucosal melanoma. Mutations affecting the TERT promoter were the most frequent of all; however, neither they nor ATRX mutations, which correlate with alternative telomere lengthening, were associated with greater telomere length. Most melanomas had potentially actionable mutations, most in components of the mitogen-activated protein kinase and phosphoinositol kinase pathways. The whole-genome mutation landscape of melanoma reveals diverse carcinogenic processes across its subtypes, some unrelated to sun exposure, and extends potential involvement of the non-coding genome in its pathogenesis. The first large, high-coverage whole-genome sequencing study of melanomas from cutaneous, acral and mucosal sites. Skin cancer subtypes sequenced Melanoma is a highly metastatic cancer with a high mutation load, and signatures in some subtypes are often associated with exposure to ultraviolet radiation. Graham Mann and colleagues report whole-genome sequencing of tumour samples from patients with melanoma, including 75 primary melanomas, 93 melanoma metastases and 15 cell lines derived from melanoma metastases. The authors compare the genomic landscapes of cutaneous, acral and mucosal subtypes of melanoma, identifying distinct mutational signatures by subtype. Cutaneous melanomas showed mutational signatures of ultraviolet radiation exposure, whereas acral and mucosal melanomas showed a lower mutation burden and more frequent complex structural rearrangements in comparison to other melanoma subtypes. Understanding the whole-genome landscapes of all melanoma subtypes is important for investigating melanoma prevention and targeted treatment.

Substantial and prolonged enhancements in stratospheric water vapor (SWV) have occurred after large‐magnitude explosive tropical volcanic eruptions, with modified tropopause entry caused by aerosol‐absorptive heating. Here, we analyze the timing and longevity of heating‐driven post‐eruption SWV changes within CMIP6‐VolMIP short‐term climate‐response experiments with the UK Earth System Model (UKESM1). We find aerosol‐absorptive heating causes peak SWV increases of 17% (∼1 ppmv) and 10% (0.5 ppmv) at 100 and 50 hPa, at ∼18 and ∼23 months after a Pinatubo‐like eruption, respectively. We track the temperature response in the tropical lower stratosphere and identify the main SWV increase occurs only after the descending aerosol heating reaches the tropopause, suggesting a key role for aerosol microphysical processes (sedimentation rate). We explore how El Niño–Southern Oscillation variability modulates this effect. Post‐eruption SWV increases are ∼80% stronger for the La Nina phase compared to the ensemble mean. Tropical upwelling strongly mediates this effect. Plain Language Summary Strong volcanic eruptions, such as the 1991 eruption of Mt Pinatubo, inject a large amount of SO2 directly into the stratosphere, thereby enhancing the stratospheric aerosol layer and causing a short‐term climatic perturbation. Another substantial part of the climatic influence is the change in stratospheric water vapor (SWV), which affects the chemical processes and the radiative budget of the atmosphere. Along with near‐instantaneous injection of water vapor into the stratosphere, volcanic eruptions can indirectly enhance the entry of water vapor into the stratosphere through aerosol‐induced tropopause heating. This work analyses Earth system model experiments designed to explore how volcanic impacts combine with internal climate variability. We find that peak SWV entry mixing ratios occur only within the second post‐eruption year, consistent with the substantially lagged timing of SWV increase seen in post‐Pinatubo satellite measurements. This analysis provides a new perspective on the temporal evolution of the observed post‐Pinatubo SWV increase and an improved quantification of its impacts. Key Points Aerosol‐induced absorptive‐heating increases stratospheric water vapor (SWV) by up to 17% at 18 months post‐eruption in a Pinatubo‐like experiment Analyzing simulations by El Niño–Southern Oscillation (ENSO) variability show an 80% larger peak SWV increase occurs if an eruption is followed by a La Niña phase The timing of peak SWV increase occurs when volcanic‐aerosol‐induced heating reaches the tropopause, with ENSO modulation of tropical upwelling

We describe Global Atmosphere 7.0 and Global Land 7.0 (GA7.0/GL7.0), the latest science configurations of the Met Office Unified Model (UM) and the Joint UK Land Environment Simulator (JULES) land surface model developed for use across weather and climate timescales. GA7.0 and GL7.0 include incremental developments and targeted improvements that, between them, address four critical errors identified in previous configurations: excessive precipitation biases over India, warm and moist biases in the tropical tropopause layer (TTL), a source of energy non-conservation in the advection scheme and excessive surface radiation biases over the Southern Ocean. They also include two new parametrisations, namely the UK Chemistry and Aerosol (UKCA) GLOMAP-mode (Global Model of Aerosol Processes) aerosol scheme and the JULES multi-layer snow scheme, which improve the fidelity of the simulation and were required for inclusion in the Global Atmosphere/Global Land configurations ahead of the 6th Coupled Model Intercomparison Project (CMIP6).In addition, we describe the GA7.1 branch configuration, which reduces an overly negative anthropogenic aerosol effective radiative forcing (ERF) in GA7.0 whilst maintaining the quality of simulations of the present-day climate. GA7.1/GL7.0 will form the physical atmosphere/land component in the HadGEM3–GC3.1 and UKESM1 climate model submissions to the CMIP6.

A growing number of general circulation models are adapting interactive sulfur and aerosol schemes to improve the representation of relevant physical and chemical processes and associated feedbacks. They are motivated by investigations of climate response to major volcanic eruptions and potential solar geoengineering scenarios. However, uncertainties in these schemes are not well constrained. Stratospheric sulfate is modulated by emissions of sulfur-containing species of anthropogenic and natural origin, including volcanic activity. While the effects of volcanic eruptions have been studied in the framework of global model intercomparisons, the background conditions of the sulfur cycle have not been addressed in such a way. Here, we fill this gap by analyzing the distribution of the main sulfur species in nine global atmospheric aerosol models for a volcanically quiescent period. We use observational data to evaluate model results. Overall, models agree that the three dominant sulfur species in terms of burdens (sulfate aerosol, OCS, and SO2) make up about 98 % stratospheric sulfur and 95 % tropospheric sulfur. However, models vary considerably in the partitioning between these species. Models agree that anthropogenic emission of SO2 strongly affects the sulfate aerosol burden in the northern hemispheric troposphere, while its importance is very uncertain in other regions, where emissions are much lower. Sulfate aerosol is the main deposited species in all models, but the values deviate by a factor of 2. Additionally, the partitioning between wet and dry deposition fluxes is highly model dependent. Inter-model variability in the sulfur species is low in the tropics and increases towards the poles. Differences are largest in the dynamically active northern hemispheric extratropical region and could be attributed to the representation of the stratospheric circulation. The differences in the atmospheric sulfur budget among the models arise from the representation of both chemical and dynamical processes, whose interplay complicates the bias attribution. Several problematic points identified for individual models are related to the specifics of the chemistry schemes, model resolution, and representation of cross-tropopause transport in the extratropics. Further model intercomparison research is needed with a focus on the clarification of the reasons for biases, given the importance of this topic for the stratospheric aerosol injection studies.

Accurately quantifying volcanic impacts on climate is a key requirement for robust attribution of anthropogenic climate change. Here we use the Unified Model – United Kingdom Chemistry and Aerosol (UM-UKCA) composition–climate model to simulate the global dispersion of the volcanic aerosol clouds from the three largest eruptions of the 20th century: 1963 Mt Agung, 1982 El Chichón, and 1991 Mt Pinatubo. The model has interactive stratospheric chemistry and aerosol microphysics, with coupled aerosol–radiation interactions for realistic composition–dynamics feedbacks. Our simulations align with the design of the Interactive Stratospheric Aerosol Model Intercomparison (ISA-MIP) “Historical Eruption SO2 Emissions Assessment”. For each eruption, we perform three-member ensemble model experiments for upper, mid-point, and lower estimates of SO2 emission, each re-initialised from a control run to approximately match the observed transition in the phase of the quasi-biennial oscillation (QBO) in the 6 months after the eruptions. With this experimental design, we assess how each eruption's emitted SO2 translates into a tropical reservoir of volcanic aerosol and analyse the subsequent dispersion to mid-latitudes. We compare the simulations to the volcanic forcing datasets (e.g. Space-based Stratospheric Aerosol Climatology (GloSSAC); Sato et al., 1993, and Ammann et al., 2003) that are used in historical integrations for the two most recent Coupled Model Intercomparison Project (CMIP) assessments. For Pinatubo and El Chichón, we assess the vertical extent of the simulated volcanic clouds by comparing modelled extinction to the Stratospheric Aerosol and Gas Experiment (SAGE-II) v7.0 satellite measurements and to 1964–1965 Northern Hemisphere ground-based lidar measurements for Agung. As an independent test for the simulated volcanic forcing after Pinatubo, we also compare simulated shortwave (SW) and longwave (LW) top-of-the-atmosphere radiative forcings to the flux anomalies measured by the Earth Radiation Budget Experiment (ERBE) satellite instrument. For the Pinatubo simulations, an injection of 10 to 14 Tg SO2 gives the best match to the High Resolution Infrared Sounder (HIRS) satellite-derived global stratospheric sulfur burden, with good agreement also with SAGE-II mid-visible and near-infra-red extinction measurements. This 10–14 Tg range of emission also generates a heating of the tropical stratosphere that is consistent with the temperature anomaly present in the ERA-Interim reanalysis. For El Chichón, the simulations with 5 and 7 Tg SO2 emission give best agreement with the observations. However, these simulations predict a much deeper volcanic cloud than represented in the GloSSAC dataset, which is largely based on an interpolation between Stratospheric Aerosol Measurements (SAM-II) satellite and aircraft measurements. In contrast, these simulations show much better agreement during the SAGE-II period after October 1984. For 1963 Agung, the 9 Tg simulation compares best to the forcing datasets with the model capturing the lidar-observed signature of the altitude of peak extinction descending from 20 km in 1964 to 16 km in 1965. Overall, our results indicate that the downward adjustment to SO2 emission found to be required by several interactive modelling studies when simulating Pinatubo is also needed when simulating the Agung and El Chichón aerosol clouds. This strengthens the hypothesis that interactive stratospheric aerosol models may be missing an important removal or re-distribution process (e.g. effects of co-emitted ash) which changes how the tropical reservoir of volcanic aerosol evolves in the initial months after an eruption. Our model comparisons also identify potentially important inhomogeneities in the CMIP6 dataset for all three eruption periods that are hard to reconcile with variations predicted in the interactive stratospheric aerosol simulations. We also highlight large differences between the CMIP5 and CMIP6 volcanic aerosol datasets for the Agung and El Chichón periods. Future research should aim to reduce this uncertainty by reconciling the datasets with additional stratospheric aerosol observations.

Aerosols have a potentially large effect on climate, particularly through their interactions with clouds, but the magnitude of this effect is highly uncertain. Large volcanic eruptions produce sulfur dioxide, which in turn produces aerosols; these eruptions thus represent a natural experiment through which to quantify aerosol-cloud interactions. Here we show that the massive 2014-2015 fissure eruption in Holuhraun, Iceland, reduced the size of liquid cloud droplets - consistent with expectations - but had no discernible effect on other cloud properties. The reduction in droplet size led to cloud brightening and global-mean radiative forcing of around minus 0.2 watts per square metre for September to October 2014. Changes in cloud amount or cloud liquid water path, however, were undetectable, indicating that these indirect effects, and cloud systems in general, are well buffered against aerosol changes. This result will reduce uncertainties in future climate projections, because we are now able to reject results from climate models with an excessive liquid-water-path response.