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We report the recovery and re-calibration of an extensive dataset of vertical profile measurements of the 1963/64 stratospheric aerosol layer measured from a two-site searchlight measurement facility at White Sands missile base and Sacramento Peak observatory, in New Mexico, US. The recovered dataset comprises 105 profiles of 550nm aerosol extinction (βp(z)) and is part of a longer program of measurements with the US Air Force Cambridge Research Laboratories (AFCRL) searchlight facility that began in February 1963. The recovered series of βp(z) profiles span the 13-month period December 1963 to December 1964 and provide a unique record of the altitude and vertical extent of the Northern Hemisphere dispersed portion of the aerosol cloud from the March 1963 Agung volcanic eruption. The data recovery methodology involved first re-digitizing the 105 original βp(z) profiles (βp(z)) from individual Figures within an AFCRL research report (Elterman, 1966a). The re-calibration involves inverting the original equation used to compute βp(z) in Elterman (1966a; 1966b) to retrieve a normalized detector response (Er(z) Er(35)) profile for each of the 105 re-digitized βp 0(z) profiles. An iterative procedure was then used to compute the re-calibration βp(z) profiles (βp Ra(z)), with the molecular extinction profile calculated with the corresponding daily molecular extinction profile calculated from local soundings, rather than the US Standard Atmosphere 1962 in the original dataset. Two-way molecular and aerosol transmittance corrections are applied using the MODTRAN (MODerate resolution atmospheric TRANsmission) code in transmission mode, applying a best-estimate aerosol phase function calculated from measurements, applied for the entire 2.76 to 35.2 km column. For the tropospheric aerosol transmittance, the AERONET aerosol phase function from White Sands High Energy Laser Systems Test Facility (HELSTF) was applied (2.76 to 10.7 km), a separate stratospheric phase function applied between 11.2 and 35.2 km, calculated from a set of particle size distributions measured by the U-2 high-altitude aircraft over a US region in the vicinity of White Sands in early 1964. Errors were estimated taking as a reference the errors determined in the computation of βp 0(z). Using available tabulated data from the original procedure the errors in the re-digitalization of βp 0(z) and in the retrieval of the Er(z) Er(35) procedures were calculated and later added to the original estimates. Both the βp R(z) and the stratospheric aerosol optical depth magnitudes showed higher magnitudes than βp 0(z) and the original stratospheric aerosol optical depth, however their magnitudes show a reasonable agreement with other contemporary observations. Both the original and recalibration datasets are being submitted to PANGAEA data repository for its storage and public access. [ABSTRACT FROM AUTHOR]

Summary: Specific sleep disorders have been linked to disease progression in different cancers. We hypothesised sleep symptom clusters would differ between cancer types. The aim of this study was to compare sleep symptom clusters in post‐treatment melanoma, breast and endometrial cancer patients. Data were collected from 124 breast cancer patients (1 male, 60 ± 15 years, 28.1 ± 6.6 kg/m2), 82 endometrial cancer patients (64.0 ± 12.5 years, 33.5 ± 10.4 kg/m2) and 112 melanoma patients (59 male, 65.0 ± 18.0 years, 29.1 ± 6.6 kg/m2). All patients completed validated questionnaires to assess sleep symptoms, including the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Functional Outcomes of Sleep Questionnaire‐10 (FOSQ‐10). Snoring, tiredness, observed apneas, age, BMI, and gender data were also collected. Binary values (PSQI, ISI, FOSQ), or continuous variables for sleepiness (ESS) and perceived sleep quality (PSQI), were created and sleep symptom clusters were identified and compared across cancer cohorts. Four distinct sleep symptom clusters were identified: minimally symptomatic (n = 152, 47.7%); insomnia‐predominant (n = 87, 24.9%); very sleepy with upper airway symptoms (n = 51, 16.3%), and severely symptomatic with severe dysfunction (n = 34, 11.1%). Breast cancer patients were significantly more likely to be in the insomnia predominant or severely symptomatic with severe dysfunction clusters, whereas melanoma patients were more likely to be minimally symptomatic or sleepy with upper airway symptoms (p <0.0001). Endometrial cancer patients were equally distributed across symptom clusters. Sleep symptom clusters vary across cancer patients. A more personalised approach to the management of sleep‐related symptoms in these patients may improve the long term quality of life and survival. [ABSTRACT FROM AUTHOR]

Nitric Acid Trihydrate (NAT) crystal formation in the absence of water ice is important for a subset of Polar Stratospheric Clouds (PSCs) and thereby ozone depletion. It has been suggested that either fragmented meteoroids or meteoric smoke particles (MSPs), or possibly both, are important as heterogeneous nuclei of these crystals. Previous work has focused on the nucleating ability of meteoric material in nitric acid in the absence of sulfuric acid. However, it is known that when immersed in stratospheric sulfuric acid droplets, metal-containing meteoric material particles partially dissolve and components can re-precipitate as silica and alumina that have different morphologies to the original meteoric material. Hence, in this study we experimentally and theoretically explore the relative role that sulfuric acid-processed meteoric smoke and meteoric fragments may play in NAT nucleation in PSCs. We compared meteoric fragments that had been recently prepared (by milling a meteorite sample) to a sample annealed under conditions designed to simulate heating during entry into the Earth's atmosphere. Whilst the addition of sulfuric acid decreased the nucleating ability of the recently milled meteoric material relative to nucleation in binary nitric acid-water solutions (at similar NAT saturation ratio), the annealed meteoric fragments nucleated NAT with a similar effectiveness in both solutions. However, combining our results with measured fluxes of meteoric material to the Earth, sedimentation modelling and recent experiments on fragmentation of incoming meteoroids, suggests that there are unlikely to be sufficient fragments to contribute to the nucleation of crystalline NAT particles. We then considered silica formed from sulfuric acid processed meteoric smoke particles. Our previous work showed that nanoparticulate silica (radius ~6 nm) is a relatively poor promoter of nucleation compared with micron scaled silica particles, which were more effective. Both materials have similar chemical and structural (crystallographically amorphous) properties, indicating size is critical. Here we account for surface curvature of primary grains using Classical Nucleation Theory (CNT) to explore this size dependence. This model is able to explain the discrepancy in nucleation effectiveness of fumed silica and fused quartz, by treating their nucleating activity (contact angle) as equal but with differing particle size (or surface curvature), assuming interfacial energies that are physically reasonable. Here we use this CNT model to present evidence that nucleation of NAT on acid processed MSPs, where the primary grain size is 10s nm, is also effective enough to contribute to NAT crystals in early season PSCs where there is an absence of ice. This study demonstrates that modelling of crystal nucleation in PSCs and resulting ozone depletion relies on accurate understanding of the transport and chemical processing of MSPs. This will affect estimated sensitivity of stratospheric chemistry to rare events such as large volcanic eruptions and long-term forecasting of ozone recovery in a changing climate. [ABSTRACT FROM AUTHOR]

Recent model inter-comparison studies highlighted model discrepancies in reproducing the climatic impacts of large explosive volcanic eruptions, calling into question the reliability of global aerosol model simulations for future scenarios. Here, we analyse the simulated evolution of the stratospheric aerosol plume following the well observed June 1991 Mt. Pinatubo eruption by six interactive stratospheric aerosol microphysics models in comparison to a range of observational data sets. Our primary focus 5 is on the uncertainties regarding initial SO2 emission following the Pinatubo eruption in 1991, 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 SO2 injection amount (ranging between 5 and 10 Tg-S), and the altitude of injection (between 18-25 km). We find that the common and main weakness among all the models is that they can not reproduce the persistence of the sulfate aerosols in the stratosphere. Most models 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, that results in a shorter e-folding time compared to the observations. Moreover, the simulations in which more than 5 Tg-S of SO2 are injected show 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 results in an overestimation of the number of particles globally during the build-up phase and an underestimation in the Southern Hemisphere, which draws attention to the importance of including processes as the ash injection and the eruption of Cerro Hudson. [ABSTRACT FROM AUTHOR]

Background: Clinical quality registries aim to identify significant variations in care and provide anonymised feedback to institutions to improve patient outcomes. Thirty‐six Australian organisations with an interest in melanoma, raised funds through three consecutive Melanoma Marches, organised by Melanoma Institute Australia, to create a national Melanoma Clinical Outcomes Registry (MelCOR). This study aimed to formally develop valid clinical quality indicators for the diagnosis and early management of cutaneous melanoma as an important step in creating the registry. Methods: Potential clinical quality indicators were identified by examining the literature, including Australian and international melanoma guidelines, and by consulting with key melanoma and registry opinion leaders. A modified two‐round Delphi survey method was used, with participants invited from relevant health professions routinely managing melanoma as well as relevant consumer organisations. Results: Nineteen participants completed at least one round of the Delphi process. 12 of 13 proposed clinical quality indictors met the validity criteria. The clinical quality indicators included acceptable biopsy method, appropriate excision margins, standardised pathology reporting, indications for sentinel lymph node biopsy, and involvement of multidisciplinary care and referrals. Conclusion: This study provides a multi‐stakeholder consensus for important clinical quality indicators that define optimal practice that will now be used in the Australian Melanoma Clinical Outcomes Registry (MelCOR). [ABSTRACT FROM AUTHOR]

In this modern era of precision medicine, molecular signatures identified from advanced omics technologies hold great promise to better guide clinical decisions. However, current approaches are often location-specific due to the inherent differences between platforms and across multiple centres, thus limiting the transferability of molecular signatures. We present Cross-Platform Omics Prediction (CPOP), a penalised regression model that can use omics data to predict patient outcomes in a platform-independent manner and across time and experiments. CPOP improves on the traditional prediction framework of using gene-based features by selecting ratio-based features with similar estimated effect sizes. These components gave CPOP the ability to have a stable performance across datasets of similar biology, minimising the effect of technical noise often generated by omics platforms. We present a comprehensive evaluation using melanoma transcriptomics data to demonstrate its potential to be used as a critical part of a clinical screening framework for precision medicine. Additional assessment of generalisation was demonstrated with ovarian cancer and inflammatory bowel disease studies. [ABSTRACT FROM AUTHOR]

This paper provides initial results from a multi-model ensemble analysis based on the volc-pinatubo-full experiment performed within the Model Intercomparison Project on the climatic response to Volcanic forcing (VolMIP) as part of the sixth phase of the Coupled Model Intercomparison Project (CMIP6). The volc-pinatubo-full experiment is based on an ensemble of volcanic forcing-only climate simulations with the same volcanic aerosol dataset across the participating models (the 1991–1993 Pinatubo period from the CMIP6-GloSSAC dataset). The simulations are conducted within an idealized experimental design where initial states are sampled consistently across models from the CMIP6-piControl simulation providing unperturbed preindustrial background conditions. The multi-model ensemble includes output from an initial set of six participating Earth system models (CanESM5, GISS-E2.1-G, IPSL-CM6A-LR, MIROC-E2SL, MPI-ESM1.2-LR and UKESM1). The results show overall good agreement between the different models on the global and hemispheric scales concerning the surface climate responses, thus demonstrating the overall effectiveness of VolMIP's experimental design. However, small yet significant inter-model discrepancies are found in radiative fluxes, especially in the tropics, that preliminary analyses link with minor differences in forcing implementation; model physics, notably aerosol–radiation interactions; the simulation and sampling of El Niño–Southern Oscillation (ENSO); and, possibly, the simulation of climate feedbacks operating in the tropics. We discuss the volc-pinatubo-full protocol and highlight the advantages of volcanic forcing experiments defined within a carefully designed protocol with respect to emerging modelling approaches based on large ensemble transient simulations. We identify how the VolMIP strategy could be improved in future phases of the initiative to ensure a cleaner sampling protocol with greater focus on the evolving state of ENSO in the pre-eruption period. [ABSTRACT FROM AUTHOR]

Summary: Background: Previous studies suggest that polygenic risk scores (PRSs) may improve melanoma risk stratification. However, there has been limited independent validation of PRS‐based risk prediction, particularly assessment of calibration (comparing predicted to observed risks). Objectives: To evaluate PRS‐based melanoma risk prediction in prospective UK and Australian cohorts with European ancestry. Methods: We analysed invasive melanoma incidence in the UK Biobank (UKB; n = 395 647, 1651 cases) and a case‐cohort nested within the Melbourne Collaborative Cohort Study (MCCS, Australia; n = 4765, 303 cases). Three PRSs were evaluated: 68 single‐nucleotide polymorphisms (SNPs) at 54 loci from a 2020 meta‐analysis (PRS68), 50 SNPs significant in the 2020 meta‐analysis excluding UKB (PRS50) and 45 SNPs at 21 loci known in 2018 (PRS45). Ten‐year melanoma risks were calculated from population‐level cancer registry data by age group and sex, with and without PRS adjustment. Results: Predicted absolute melanoma risks based on age and sex alone underestimated melanoma incidence in the UKB [ratio of expected/observed cases: E/O = 0·65, 95% confidence interval (CI) 0·62–0·68] and MCCS (E/O = 0·63, 95% CI 0·56–0·72). For UKB, calibration was improved by PRS adjustment, with PRS50‐adjusted risks E/O = 0·91, 95% CI 0·87–0·95. The discriminative ability for PRS68‐ and PRS50‐adjusted absolute risks was higher than for risks based on age and sex alone (Δ area under the curve 0·07–0·10, P < 0·0001), and higher than for PRS45‐adjusted risks (Δ area under the curve 0·02–0·04, P < 0·001). Conclusions: A PRS derived from a larger, more diverse meta‐analysis improves risk prediction compared with an earlier PRS, and might help tailor melanoma prevention and early detection strategies to different risk levels. Recalibration of absolute risks may be necessary for application to specific populations. [ABSTRACT FROM AUTHOR]

Oncogenic alterations to DNA are not transforming in all cellular contexts1,2. This may be due to pre-existing transcriptional programmes in the cell of origin. Here we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet or under the nails3. We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma and enrichment for CRKL amplifications in acral melanoma. We modelled these changes in transgenic zebrafish models and found that CRKL-driven tumours formed predominantly in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin and limb melanocytes, when compared with body melanocytes, revealed a positional identity gene programme typified by posterior HOX13 genes. This positional gene programme synergized with CRKL to amplify insulin-like growth factor (IGF) signalling and drive tumours at acral sites. Abrogation of this CRKL-driven programme eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.In a zebrafish model of human cutaneous and acral melanomas, CRKL amplification causes tumours to favour a fin location, indicating that tumour location is determined by both the driver oncogenes and the pre-existing positional identity gene program. [ABSTRACT FROM AUTHOR]

A new experimental system is described for studying the pyrolysis of the refractory organic constituents in cosmic dust during atmospheric entry. The pyrolysis kinetics of meteoritic fragments (CM2 and CV3 carbonaceous chondrites, radius = 36–100 μm) were measured by mass spectrometric detection of CO2 and SO2 at temperatures between 625 and 1300 K, with most carbon being lost between 700 and 800 K. The complex time‐resolved kinetic behavior is consistent with two organic components—one significantly more refractory than the other, which probably correspond to the insoluble and soluble organic fractions, respectively. The measured temperature‐dependent pyrolysis rates were then incorporated into the Leeds Chemical Ablation Model, which demonstrates that organic pyrolysis should be detectable using a high performance/large aperture radar. Atomic force microscopy was used to show that although the residual meteoritic particles became more brittle after organic pyrolysis, they also became slightly harder, withstanding stresses that are at least three orders of magnitude higher than would be encountered during atmospheric entry. This suggests that most cosmic dust particles (radius <100 μm) will not fragment during entry into the atmosphere as a result of organic pyrolysis, although a subset of slow‐moving, low density particles mostly from Jupiter‐family comets could fragment. Plain Language Summary: Cosmic dust particles, particularly when they originate from comets moving into the inner solar system, are composed of silicate mineral grains bound together in a matrix of very stable organic material. During entry into a planetary atmosphere, these particles frequently heat above 800 K, at which point this organic material decomposes into mainly carbon dioxide. In this study we measured the rate of decomposition of organics in micron‐sized meteoritic particles, and showed that it is fast enough that organic decomposition should be detectable by high performance radars. We also showed that the particles become slightly harder after organic decomposition, so these particles should not fragment during atmospheric entry. The exception may be slow‐moving fluffy particles of the type recently observed in the ROSETTA mission to comet 67P. Key Points: The temperature‐dependent pyrolysis kinetics of organic matter in two carbonaceous meteorites has been measuredMeteoritic particles become slightly harder after carbon pyrolysis so only slow‐moving, low density particles should fragment during entryOrganic pyrolysis should be detectable in the head echo measured using a high performance/large aperture radar [ABSTRACT FROM AUTHOR]

Until now our understanding of the 11-year solar cycle signal (SCS) in stratospheric ozone has been largely based on high-quality but sparse ozone profiles from the Stratospheric Aerosol and Gas Experiment (SAGE) II or coarsely resolved ozone profiles from the nadir-viewing Solar Backscatter Ultraviolet Radiometer (SBUV) satellite instruments. Here, we analyse 16 years (2005–2020) of ozone profile measurements from the Microwave Limb Sounder (MLS) instrument on the Aura satellite to estimate the 11-year SCS in stratospheric ozone. Our analysis of Aura-MLS data suggests a single-peak-structured SCS profile (about 3 % near 4 hPa or 40 km) in tropical stratospheric ozone, which is significantly different to the SAGE II and SBUV-based double-peak-structured SCS. We also find that MLS-observed ozone variations are more consistent with ozone from our control model simulation that uses Naval Research Laboratory (NRL) v2 solar fluxes. However, in the lowermost stratosphere modelled ozone shows a negligible SCS compared to about 1 % in Aura-MLS data. An ensemble of ordinary least squares (OLS) and three regularised (lasso, ridge and elastic net) linear regression models confirms the robustness of the estimated SCS. In addition, our analysis of MLS and model simulations shows a large SCS in the Antarctic lower stratosphere that was not seen in earlier studies. We also analyse chemical transport model simulations with alternative solar flux data. We find that in the upper (and middle) stratosphere the model simulation with Solar Radiation and Climate Experiment (SORCE) satellite solar fluxes is also consistent with the MLS-derived SCS and agrees well with the control simulation and one which uses Spectral and Total Irradiance Reconstructions (SATIRE) solar fluxes. Hence, our model simulation suggests that with recent adjustments and corrections, SORCE data can be used to analyse effects of solar flux variations. Furthermore, analysis of a simulation with fixed solar fluxes and one with fixed (annually repeating) meteorology confirms that the implicit dynamical SCS in the (re)analysis data used to force the model is not enough to simulate the observed SCS in the middle and upper stratospheric ozone. Finally, we argue that the overall significantly different SCS compared to previous estimates might be due to a combination of different factors such as much denser MLS measurements, almost linear stratospheric chlorine loading changes over the analysis period, variations in the stratospheric dynamics as well as relatively unperturbed stratospheric aerosol layer that might have influenced earlier analyses. [ABSTRACT FROM AUTHOR]

Survival analysis is a branch of statistics that deals with both the tracking of time and the survival status simultaneously as the dependent response. Current comparisons of survival model performance mostly center on clinical data with classic statistical survival models, with prediction accuracy often serving as the sole metric of model performance. Moreover, survival analysis approaches for censored omics data have not been thoroughly investigated. The common approach is to binarize the survival time and perform a classification analysis. Here, we develop a benchmarking design, SurvBenchmark, that evaluates a diverse collection of survival models for both clinical and omics data sets. SurvBenchmark not only focuses on classical approaches such as the Cox model but also evaluates state-of-the-art machine learning survival models. All approaches were assessed using multiple performance metrics; these include model predictability, stability, flexibility, and computational issues. Our systematic comparison design with 320 comparisons (20 methods over 16 data sets) shows that the performances of survival models vary in practice over real-world data sets and over the choice of the evaluation metric. In particular, we highlight that using multiple performance metrics is critical in providing a balanced assessment of various models. The results in our study will provide practical guidelines for translational scientists and clinicians, as well as define possible areas of investigation in both survival technique and benchmarking strategies. [ABSTRACT FROM AUTHOR]

This paper provides initial results from a multi-model ensemble analysis based on the volc-pinatubo-full experiment performed within the Model Intercomparison Project on the climatic response to volcanic forcing (VolMIP) as part of the sixth phase of the Coupled Model Intercomparison Project (CMIP6). The volc-pinatubo-full experiment is based on ensemble of volcanic forcing-only climate simulations with the same volcanic aerosol dataset across the participating models (the 1991-1993 Pinatubo period from the CMIP6-GloSSAC dataset). The simulations are conducted within an idealized experimental design where initial states are sampled consistently across models from the CMIP6-piControl simulation providing unperturbed pre-industrial background conditions. The multi-model ensemble includes output from an initial set of six participating Earth system models (CanESM5, GISS-E2.1-G, IPSL-CM6A-LR, MIROC-E2SL, MPI-ESM1.2-LR and UKESM1). The results show overall good agreement between the different models on the global and hemispheric scale concerning the surface climate responses, thus demonstrating the overall effectiveness of VolMIP's experimental design. However, small yet significant inter-model discrepancies are found in radiative fluxes especially in the tropics, that preliminary analyses link with minor differences in forcing implementation, model physics, notably aerosol-radiation interactions, the simulation and sampling of El Niño-Southern Oscillation (ENSO) and, possibly, the simulation of climate feedbacks operating in the tropics. We discuss the volc-pinatubo-full protocol and highlight the advantages of volcanic forcing experiments defined within a carefully designed protocol with respect to emerging modeling approaches based on large ensemble transient simulations. We identify how the VolMIP strategy could be improved in future phases of the initiative to ensure a cleaner sampling protocol with greater focus on the evolving state of ENSO in the pre-eruption period. [ABSTRACT FROM AUTHOR]

Background: Cancer patients often describe poor sleep quality and sleep disruption as contributors to poor quality of life (QoL). In a cross-sectional study of post-treatment breast, endometrial, and melanoma cancer patients, we used actigraphy to quantify sleep regularity using the sleep regularity index (SRI), and examined relationships with reported sleep symptoms and QoL. Methods: Participants were recruited post-primary treatment (35 diagnosed with breast cancer, 24 endometrial cancer, and 29 melanoma) and wore an actigraphy device for up to 2 weeks and SRI was calculated. Self-report questionnaires for cancer-related QoL [European Organization for Research and Treatment of Cancer EORTC (QLQ-C30)] were completed. Data were compared using analysis of variance (ANOVA) or Chi-Square tests. Multivariate linear regression analysis was used to determine independent variable predictors for questionnaire-derived data. Results: Age distribution was similar between cohorts. Endometrial and breast cancer cohorts were predominantly female, as expected, and body mass index (BMI) was higher in the endometrial cancer cohort, followed by breast and melanoma. There were no differences between tumor groups in: total sleep time, sleep onset latency, bedtime, and SRI (breast 80.9 ± 8.0, endometrial 80.3 ± 12.2, and melanoma 81.4 ± 7.0) (all p > 0.05). A higher SRI was associated with both better functional and symptom scores, including increased global QoL, better physical functioning, less sleepiness and fatigue, better sleep quality, and associated with less nausea/vomiting, dyspnea, and diarrhea (all p < 0.05). Conclusion: In cancer patients post-treatment, greater sleep regularity is associated with increased global QoL, as well as better physical functioning and fewer cancer related symptoms. Improving sleep regularity may improve QoL for cancer patients. [ABSTRACT FROM AUTHOR]

We report the recovery and processing methodology of the first ever multi-year lidar dataset of the stratospheric aerosol layer. A Q-switched ruby lidar measured 66 vertical profiles of 694 nm attenuated backscatter at Lexington, Massachusetts, between January 1964 and August 1965, with an additional nine profile measurements conducted from College, Alaska, during July and August 1964. We describe the processing of the recovered lidar backscattering ratio profiles to produce mid-visible (532 nm) stratospheric aerosol extinction profiles (sAEP 532) and stratospheric aerosol optical depth (sAOD 532) measurements, utilizing a number of contemporary measurements of several different atmospheric variables. Stratospheric soundings of temperature and pressure generate an accurate local molecular backscattering profile, with nearby ozone soundings determining the ozone absorption, which are used to correct for two-way ozone transmittance. Two-way aerosol transmittance corrections are also applied based on nearby observations of total aerosol optical depth (across the troposphere and stratosphere) from sun photometer measurements. We show that accounting for these two-way transmittance effects substantially increases the magnitude of the 1964/1965 stratospheric aerosol layer's optical thickness in the Northern Hemisphere mid-latitudes, then ∼ 50 % larger than represented in the Coupled Model Intercomparison Project 6 (CMIP6) volcanic forcing dataset. Compared to the uncorrected dataset, the combined transmittance correction increases the sAOD 532 by up to 66 % for Lexington and up to 27 % for Fairbanks, as well as individual sAEP 532 adjustments of similar magnitude. Comparisons with the few contemporary measurements available show better agreement with the corrected two-way transmittance values. Within the January 1964 to August 1965 measurement time span, the corrected Lexington sAOD 532 time series is substantially above 0.05 in three distinct periods, October 1964, March 1965, and May–June 1965, whereas the 6 nights the lidar measured in December 1964 and January 1965 had sAOD values of at most ∼ 0.03. The comparison with interactive stratospheric aerosol model simulations of the Agung aerosol cloud shows that, although substantial variation in mid-latitude sAOD 532 are expected from the seasonal cycle in the stratospheric circulation, the Agung cloud's dispersion from the tropics would have been at its strongest in winter and weakest in summer. The increasing trend in sAOD from January to July 1965, also considering the large variability, suggests that the observed variations are from a different source than Agung, possibly from one or both of the two eruptions that occurred in 1964/1965 with a Volcanic Explosivity Index (VEI) of 3: Trident, Alaska, and Vestmannaeyjar, Heimaey, south of Iceland. A detailed error analysis of the uncertainties in each of the variables involved in the processing chain was conducted. Relative errors for the uncorrected sAEP 532 were 54 % for Fairbanks and 44 % Lexington. For the corrected sAEP 532 the errors were 61 % and 64 %, respectively. The analysis of the uncertainties identified variables that with additional data recovery and reprocessing could reduce these relative error levels. Data described in this work are available at 10.1594/PANGAEA.922105 (Antuña-Marrero et al., 2020a). [ABSTRACT FROM AUTHOR]

Until now our understanding of the 11-year solar cycle signal (SCS) in stratospheric ozone has been largely based on high quality but sparse ozone profiles from the Stratospheric Aerosol and Gas Experiment (SAGE) II or coarsely resolved ozone profiles from the nadir-viewing Solar Backscatter Ultraviolet Radiometer (SBUV) satellite instruments. Here, we analyse 16 years (2005-2020) of ozone profile measurements from the Microwave Limb Sounder (MLS) instrument on the Aura satellite to estimate the 11-year SCS in stratospheric ozone. Our analysis of Aura-MLS data suggests a single-peak-structured SCS profile (about 3% near 4 hPa or 40 km) in tropical stratospheric ozone, which is significantly different to the SAGE II and SBUV-based double-peak-structured SCS. We also find that MLS-observed ozone variations are more consistent with ozone from our control model simulation that uses Naval Research Laboratory (NRL) v2 solar fluxes. However, in the lowermost stratosphere modelled ozone shows a negligible SCS compared to about 1% in Aura-MLS data. An ensemble of Ordinary Least Square (OLS) and three regularised (Lasso, Ridge and ElasticNet) linear regression models confirms the robustness of the estimated SCS. Our analysis of MLS and model simulations also shows a large SCS in the Antarctic lower stratosphere that was not seen in earlier studies. We also analyse chemical transport model simulations with alternative solar flux data. We find that in the upper (and middle) stratosphere the model simulation with Solar Radiation and Climate Experiment (SORCE) satellite solar fluxes is also consistent with the MLS-derived SCS and agrees well with the control simulation and one which uses Spectral and Total Irradiance Reconstructions (SATIRE) solar fluxes. Hence, our model simulation suggests that with recent adjustments and corrections, SORCE solar fluxes can be used to analyse effects of solar flux variations. Finally, we argue that the overall significantly different SCS compared to earlier estimates might be due to a combination of different factors such as much denser MLS measurements, almost linear stratospheric chlorine loading changes over the analysis period, as well as a stratospheric aerosol layer relatively unperturbed by major volcanic eruptions. [ABSTRACT FROM AUTHOR]

Reconstructions of volcanic aerosol radiative forcing are required to understand past climate variability. Currently, reconstructions of pre‐20th century volcanic forcing are derived from sulfate concentrations measured in polar ice cores, mainly using a relationship between the average ice‐sheet sulfate deposition and stratospheric sulfate aerosol burden based on a single explosive eruption—the 1991 eruption of Mt. Pinatubo. Here we estimate volcanic radiative forcings and associated uncertainty ranges from ice‐core sulfate records of eight of the largest bipolar deposition signals in the last 2,500 years using statistical emulation of a perturbed parameter ensemble of aerosol‐climate model simulations of explosive eruptions. Extensive sampling of different combinations of eruption source parameters using the emulators reveals that a very wide range of eruptions in different seasons with different sulfur dioxide emissions, eruption latitudes, and emission altitudes produce ice‐sheet sulfate deposition consistent with ice‐core records. Consequently, we find a large range in the volcanic forcing that can be directly attributed to the unknown eruption source parameters. We estimate that the uncertainty in volcanic forcing caused by many plausible eruption realizations leads to uncertainties in the global mean surface cooling of around 1°C for the largest unidentified historical eruptions. Our emulators are available online (https://cemac.github.io/volcanic-forcing-deposition) where eruption realizations for given ice‐sheet sulfate depositions can be explored. Plain Language Summary: Explosive volcanic eruptions inject sulfur into the atmosphere, forming sulfate particles that reflect sunlight and cause surface cooling. To understand past climate variability it is important to quantify the climate effects of historical eruptions. However, there are no direct observations of the sulfur emissions and cooling from eruptions that occurred hundreds of years ago, and volcanic climate effects must be inferred from indirect measurements. Volcanic sulfate is deposited onto Earth's surface and can be found in layers of polar ice. Ice‐core sulfate records are used to identify the occurrence of past eruptions, and the size of the sulfate signals is used to estimate the amount of sulfate that was present in the atmosphere and consequently the climatic effect of the eruption. We explored the uncertainty in this calculation by using climate model simulations and novel statistics to infer the properties of eruptions that could lead to sulfate deposition that matches that from ice‐core records. We found there are many eruption scenarios that could lead to the same polar sulfate deposition but have different resulting magnitudes of surface cooling. Consequently, there is a large uncertainty in the climatic effect of historical eruptions, which affects our understanding of past climate variability. Key Points: We use an aerosol‐climate model and statistical emulation to find eruption source parameters from eight bipolar sulfate deposition signalsPlausible eruptions have a wide range in sulfur dioxide emissions and latitude, and consequently, a large range in radiative forcingResulting uncertainties in global mean surface cooling for the largest unidentified historical eruptions are on the order of 1°C [ABSTRACT FROM AUTHOR]

Germline mutations in CDKN2A greatly increase risk of developing cutaneous melanoma. We have constructed a risk prediction model, Familial Risk Assessment of Melanoma (FRAMe), for estimating the likelihood of carrying a heritable CDKN2A mutation among Australian families, where the prevalence of these mutations is low. Using logistic regression, we analysed characteristics of 299 Australian families recruited through the Sydney site of GenoMEL (international melanoma genetics consortium) with at least three cases of cutaneous melanoma (in situ and invasive) among first-degree blood relatives, for predictors of the presence of a pathogenic CDKN2A mutation. The final multivariable prediction model was externally validated in an independent cohort of 61 melanoma kindreds recruited through GenoMEL Queensland. Family variables independently associated with the presence of a CDKN2A mutation in a multivariable model were number of individuals diagnosed with melanoma under 40 years of age, number of individuals diagnosed with more than one primary melanoma, and number of individuals blood related to a melanoma case in the first degree diagnosed with any cancer excluding melanoma and non-melanoma skin cancer. The number of individuals diagnosed with pancreatic cancer was not independently associated with mutation status. The risk prediction model had an area under the receiver operating characteristic curve (AUC) of 0.851 (95% CI 0.793, 0.909) in the training dataset, and 0.745 (95%CI 0.612, 0.877) in the validation dataset. This model is the first to be developed and validated using only Australian data, which is important given the higher rate of melanoma in the population. This model will help to effectively identify families suitable for genetic counselling and testing in areas of high ambient ultraviolet radiation. A user-friendly electronic nomogram is available at www.melanomarisk.org.au. [ABSTRACT FROM AUTHOR]

Purpose: Psychological interventions targeting fear of cancer recurrence (FCR) are effective in reducing fear and distress. Process evaluations are an important, yet scarce adjunct to published intervention trials, despite their utility in guiding the interpretation of study outcomes and optimizing intervention design for broader implementation. Accordingly, this paper reports the findings of a process evaluation conducted alongside a randomized controlled trial of a psychological intervention for melanoma patients. Methods: Men and women with a history of Stage 0–II melanoma at high-risk of developing new primary disease were recruited via High Risk Melanoma Clinics across Sydney, Australia and randomly allocated to receive the psychological intervention (n = 80) or usual care (n = 84). Intervention participants received a tailored psycho-educational resource and three individual psychotherapeutic sessions delivered via telehealth. Qualitative and quantitative data on intervention context, processes, and delivery (reach, dose, and fidelity), and mechanisms of impact (participant responses, moderators of outcome) were collected from a range of sources, including participant surveys, psychotherapeutic session audio-recordings, and clinical records. Results: Almost all participants reported using the psycho-educational resource (97%), received all intended psychotherapy sessions (96%), and reported high satisfaction with both intervention components. Over 80% of participants would recommend the intervention to others, and a small proportion (4%) found discussion of melanoma-related experiences confronting. Perceived benefits included enhanced doctor-patient communication, talking more openly with family members about melanoma, and improved coping. Of potential moderators, only higher FCR severity at baseline (pre-intervention) was associated with greater reductions in FCR severity (primary outcome) at 6-month follow-up (primary endpoint). Conclusions: Findings support the acceptability and feasibility of a psychological intervention to reduce FCR amongst individuals at high risk of developing another melanoma. Implementation into routine melanoma care is an imperative next step, with FCR screening recommended to identify those most likely to derive the greatest psychological benefit. [ABSTRACT FROM AUTHOR]

As part of the Model Intercomparison Project on the climatic response to Volcanic forcing (VolMIP), several climate modeling centers performed a coordinated pre-study experiment with interactive stratospheric aerosol models simulating the volcanic aerosol cloud from an eruption resembling the 1815 Mt. Tambora eruption (VolMIP-Tambora ISA ensemble). The pre-study provided the ancillary ability to assess intermodel diversity in the radiative forcing for a large stratospheric-injecting equatorial eruption when the volcanic aerosol cloud is simulated interactively. An initial analysis of the VolMIP-Tambora ISA ensemble showed large disparities between models in the stratospheric global mean aerosol optical depth (AOD). In this study, we now show that stratospheric global mean AOD differences among the participating models are primarily due to differences in aerosol size, which we track here by effective radius. We identify specific physical and chemical processes that are missing in some models and/or parameterized differently between models, which are together causing the differences in effective radius. In particular, our analysis indicates that interactively tracking hydroxyl radical (OH) chemistry following a large volcanic injection of sulfur dioxide (SO2) is an important factor in allowing for the timescale for sulfate formation to be properly simulated. In addition, depending on the timescale of sulfate formation, there can be a large difference in effective radius and subsequently AOD that results from whether the SO2 is injected in a single model grid cell near the location of the volcanic eruption, or whether it is injected as a longitudinally averaged band around the Earth. [ABSTRACT FROM AUTHOR]

Estimates of seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have been hampered by inadequate assay sensitivity and specificity. Using an enzyme-linked immunosorbent assay-based approach that combines data about immunoglobulin G responses to both the nucleocapsid and spike receptor binding domain antigens, we show that excellent sensitivity and specificity can be achieved. We used this assay to assess the frequency of virus-specific antibodies in a cohort of elective surgery patients in Australia and estimated seroprevalence in Australia to be 0.28% (95% Confidence Interval, 0-1.15%). These data confirm the low level of transmission of SARS-CoV-2 in Australia before July 2020 and validate the specificity of our assay. [ABSTRACT FROM AUTHOR]

Background: The study aimed to estimate the prevalence of active or previous SARS‐CoV‐2 infection in asymptomatic adults admitted for elective surgery in Australian hospitals. This surveillance activity was established as part of the National Pandemic Health Intelligence Plan. Methods: Participants (n = 3037) were recruited from 11 public and private hospitals in four states (NSW, Vic, SA and WA) between 2 June and 17 July 2020, with an overall 66% participation rate. Presence of SARS‐CoV‐2 viral RNA was assessed by Reverse Transcriptase ‐ Polymerase Chain Reaction (RT‐PCR) analysis of nasopharyngeal swabs taken after induction of anaesthesia. Presence of anti‐SARS‐CoV‐2 antibodies was assessed by analysis of serum collected at the same time using a novel dual‐antigen ELISA assay. Results: No patient (0/3010) returned a positive RT‐PCR result. The Bayesian estimated prevalence of active infection of 0.02% (95% probability interval 0.00–0.11%), with the upper endpoint being 1 in 918. Positive serology (IgG) was observed in 15 of 2991 patients, with a strong positive in five of those individuals (Bayesian estimated seroprevalence 0.16%; 95% probability interval 0.00–0.47%). Conclusion: These results confirm that during periods of low community prevalence of SARS‐CoV‐2 elective surgery patients without fever or respiratory symptoms had a very low prevalence of active SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

We report the recovery and processing methodology of the first ever multi-year lidar dataset of the stratospheric aerosol layer. A Q-switched Ruby lidar measured 66 vertical profiles of 694nm attenuated backscatter at Lexington, Massachusetts between January 1964 and August 1965, with an additional 9 profile measurements conducted from College, Alaska during July and August 1964. We describe the processing of the recovered lidar backscattering ratio profiles to produce mid-visible (532nm) stratospheric aerosol extinction profiles (sAEP532) and stratospheric aerosol optical depth (sAOD532) measurements, utilizing a number of contemporary measurements of several different atmospheric variables. Stratospheric soundings of temperature, and pressure generate an accurate local molecular backscattering profile, with nearby ozone soundings determining the ozone absorption, those profiles then used to correct for two-way ozone transmittance. Two-way aerosol transmittance corrections were also applied based on nearby observations of total aerosol optical depth (across the troposphere and stratosphere) from sun photometer measurements . We show the two-way transmittance correction has substantial effects on the retrieved sAEP532 and sAOD532, calculated without the corrections resulting in substantially lower values of both variables, as it was not applied in the original processing producing the lid ar scattering ratio profiles we rescued. The combined transmittance corrections causes the aerosol extinction to increase by 67 % for Lexington and 27 % for Fairbanks, for sAOD532 the increases 66 % and 26 % respectively. Comparing the magnitudes of the aerosol extinction and sAOD with the few contemporary available measurements reported show a better agreement in the case of the two way transmittance corrected values. The sAEP and sAOD timeseries at Lexington show a surprisingly large degree of variability, three periods where the stratospheric aerosol layer had suddenly elevated optical thickness, the highest sAOD532 of 0.07 measured at the end of March 1965. The two other periods of enhanced sAOD532 are both two-month periods where the lidars show more than 1 night where ret rieved sAOD532 exceeded 0.05: in January and February 1964 and November and December 1964. Interactive stratospheric aerosol model simulations of the 1963 Agung cloud illustrate that although substantial variation in mid-latitude sAOD532 is expected from the seasonal cycle in the Brewer-Dobson circulation, the Agung cloud dispersion will have caused much slower increase than the more episodic variations observed, with also different timing, elevated optical thickness from Agung occurring in winter and spring. The abruptness and timing of the steadily increasing sAOD from January to July 1965 suggests this variation was from a different source than Agung, possibly from one or both of the two VEI3 eruptions that occurred in 1964/65: Trident, Alaska and Vestmannaeyjar, Heimey, south of Iceland. A detailed error analysis of the uncertainties in each of the variables involved in the processing chain was conducted, relative errors of 54 % for Fairbanks and 44 % Lexington for the uncorrected sAEP532, corrected sAEP532 of 61 % and 64 % respectively. The analysis of the uncertainties identified variables that, with additional data recovery and reprocessing could reduce these relative error levels. Data described in this work are available at https://doi.pangaea.de/10.1594/PANGAEA.922105 (Dataset in Review) (Antuña-Marrero et al., 2020a). [ABSTRACT FROM AUTHOR]