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Background: People with severe asthma remain at risk of toxicity from maintenance oral corticosteroid (OCS) use and/or frequent OCS burst therapy. Cumulative exposures above 500–1000 mg prednisolone are associated with adverse effects, and recently OCS stewardship principles were promulgated to guide OCS prescription. Aims: To examine real‐world registry data to quantify OCS burden, ascertain trends over time in prescription and assess whether opportunities to implement steroid‐sparing strategies were utilised. Methods: Participants were enrolled in the Australasian Severe Asthma Registry for the period 2013–2021. Assessments were taken at enrolment and then annual follow‐up, which included asthma control and OCS use. Descriptive analyses were performed, and subgroups were compared at baseline and over time. Results: Nine hundred and twenty‐four participants were evaluated and 215/924 (23%) were taking maintenance OCS at baseline, with 44% and 32% of participants having exposure to ≥500 or 1000 mg of OCS respectively in the prior year. Twelve months later, an additional 10% and 9% of participants reached cumulative doses of 500 or 1000 mg. People exceeding thresholds had ongoing poor asthma control. At baseline, 240/924 (26%) people were treated with asthma biological therapy. An additional 83 (12%) participants were identified as potentially benefiting from this steroid‐sparing medication. Of these patients, only 23% commenced a biologic agent in the next 12 months. Conclusions: A large national asthma registry identifies exposure to toxic cumulative doses of OCS in more than a third of participants, with further subsequent cumulative dose escalation over 2 years. Steroid‐sparing strategies were often not employed, highlighting the need for implementation of OCS stewardship initiatives. [ABSTRACT FROM AUTHOR]

Introduction: Asthma poses a significant burden for the Australian population. Understanding severe exacerbation rates, and steroid-related burden for adults diagnosed with asthma stands to offer insights into how this could be reduced. Methods: Electronic medical records (EMR) and questionnaires from the Optimum Patient Care Research Database Australia (OPCRDA) were utilised retrospectively. OPCRDA is a real-world database with > 800,000 medical records from Australian primary care practices. Outcomes were severe asthma exacerbations in Australian adults, over a 12-month period, stratified by Global Initiative for Asthma (GINA) treatment intensity steps, and steroid associated comorbidities. Results: Of the 7868 adults treated for asthma, 19% experienced at least one severe exacerbation in the last 12-months. Severe exacerbation frequency increased with treatment intensity (≥ 1 severe exacerbation GINA 1 13%; GINA 4 23%; GINA 5a 33% and GINA 5b 28%). Questionnaire participants reported higher rates of severe exacerbations than suggested from their EMR (32% vs 23%) especially in steps 1, 4 and 5. Patients repeatedly exposed to steroids had an increased risk of osteoporosis (OR 1.95, 95% CI 1.43– 2.66) and sleep apnoea (OR 1.78, 95% CI 1.30– 2.46). Conclusion: The Australian population living with GINA 1, 4, 5a and 5b asthma have high severe exacerbation rates and steroid-related burden, especially when compared to other first world countries, with these patients needing alternative strategies or possibly specialist assessment to better manage their condition. [ABSTRACT FROM AUTHOR]

With the liberalization and deregulation of the power industry, the power market presents increasingly invisible dynamics and uncertainty. Establishing an effective price forecasting model has always been an important issue for power market participants to avoid risks and maximize economic benefits. However, due to the inherent characteristics of high frequency and high volatility of electricity price data, it is still a difficult and challenging problem to achieve high-precision forecasting. To overcome these difficulties, this study constructed a novel multivariate electric price bi-forecasting system based on the proposed linear operator combination mechanism and deep learning model. Specifically, improved complete ensemble empirical mode decomposition with adaptive noise (ICEEMDAN) is used for data preprocessing, while the multiobjective golden eagle optimization algorithm (MOGEO) optimized deep belief network and bidirectional long short-term memory network are used as the main prediction models for realizing two forecasting modes of point forecast and interval forecast by a multi-input multi-output structure simultaneously. To verify the model forecasting ability and effectiveness, four datasets from Australia (New South Wales) from 2020.7 to 2021.1 are selected for experiments. According to the empirical results, the mean absolute percentage error results of the designed forecasting strategy in point forecasting are within 4% for the four datasets, and the average coverage width criterion values in interval forecasting are all approximately 0.3. The results show that the system has good electricity price forecasting ability and can help policy-makers better understand market dynamics and develop more effective market regulation and intervention measures. • A novel electric price multi-bi-forecasting is constructed using MIMO scheme. • Multi-variable forecast scheme is adopted using the electric price and load data. • A new combination mechanism is introduced to combine the member models. • A superior optimizer is introduced in this system to realize two functions. [ABSTRACT FROM AUTHOR]

Objective: To estimate the level of dispensing of oral corticosteroids (OCS) for managing asthma in Australia, with a particular focus on the cumulative dispensing of doses associated with long term toxicity (≥ 1000 mg prednisolone‐equivalent). Design: Retrospective cohort study; analysis of 10% random sample of Pharmaceutical Benefits Scheme (PBS) dispensing data. Participants, setting: People aged 12 years or more treated for asthma during 2014–2018, according to dispensing of controller inhaled corticosteroids (ICS). Main outcome measures: Number of people dispensed OCS for managing asthma during 2014–2018; proportion who were cumulatively dispensed at least 1000 mg prednisolone‐equivalent. The secondary outcome was the number of people dispensed at least 1000 mg prednisolone‐equivalent during 2018, stratified by inhaler controller dose and use. Results: 124 011 people had been dispensed at least two prescriptions of ICS during 2014–2018 and met the study definition for asthma, of whom 64 112 (51.7%) had also been dispensed OCS, including 34 580 (27.9% of the asthma group) cumulatively dispensed 1000 mg prednisolone‐equivalent or more. Of 138 073 people dispensed OCS at this level, 68 077 (49%) were patients with airway diseases. Dispensing of diabetes and osteoporosis medications was more common for people cumulatively dispensed 1000 mg prednisolone‐equivalent or more. During 2018, 4633 people with asthma using high dose ICS controllers were dispensed 1000 mg prednisolone‐equivalent or more, for 2316 of whom (50%) controller use was inadequate. Conclusions: Cumulative exposure to OCS in Australia reaches levels associated with toxicity in one‐quarter of patients with asthma using ICS. Cumulative dispensing of potentially toxic OCS amounts often accompanies inadequate inhaler controller dispensing. Better approaches are needed to improve adherence to controller therapy, improve outcomes for people with asthma, and to minimise the use and toxicity of OCS. [ABSTRACT FROM AUTHOR]

Severe asthma leads to debilitating symptoms for patients and excessive socioeconomic burden for the community. Comprehensive models of care are required to address complex issues, risk factors and comorbidities in patients with severe asthma, and to identify patients most appropriate for specialised treatments. Dedicated severe asthma services improve asthma control, reduce asthma exacerbations and hospital admissions, and improve quality of life. Currently, diverse models of care exist for managing severe asthma across Australia. Most referrals to severe asthma services are from respiratory physicians seeking a second opinion or from primary care for poorly controlled asthma. Despite benefits of specialised severe asthma services, many patients are not referred and resources are limited, often resulting in long waiting times. Patient referral is often unstructured and there are considerable variations in the management of severe asthma with limited access to other health care professionals such as speech pathologists and dieticians, and restricted scope to optimise patient work‐up before referral. Ongoing communication between the specialist and referring clinician is essential for continuity of care but is often lacking. Referral pathways can be optimised by developing referral criteria and guidelines to triage patients with severe asthma and to improve resource efficiency. Additional education and tools for assessing and managing severe asthma are needed, and mechanisms should be developed for involving primary care in the management of stabilised patients. Strategies to increase patient access to multidisciplinary services are recommended. [ABSTRACT FROM AUTHOR]

Severe asthma encompasses treatment-refractory asthma and difficult-to-treat asthma. There are a number of barriers in primary, secondary and tertiary settings which compromise optimal care for severe asthma in Australia. Guidelines recommend a multidimensional assessment of severe asthma, which includes confirming the diagnosis, severity and phenotype and identifying and treating comorbidities and risk factors. This approach has been found to improve severe asthma symptoms and quality of life and reduce exacerbations. Primary care providers can contribute significantly to the multidimensional approach for severe asthma by performing spirometry, optimising therapy and addressing risk factors such as non-adherence and smoking before referring the patient to a respiratory physician for review. Primary care practitioners are encouraged to remain engaged with the management of a patient with severe asthma following specialist review by assisting with community-based allied health referrals, managing general medical comorbidities and administering prescribed biological therapies. Specialists can support primary care by providing advice to individuals with indeterminate diagnosis, streamlining investigation and management of unrecognised risk factors and complex comorbidities, optimising treatment for severe or difficult asthma including assessment of suitability for and, if appropriate, initiating advanced therapies such as biological therapies. When discharging patients back to primary care, specialists should provide clear recommendations regarding ongoing management and should specify the indications requiring further specialist review, ideally offering a streamlined re-referral pathway. [ABSTRACT FROM AUTHOR]

The treatment landscape in severe asthma is changing rapidly, with multiple new therapies emerging that promise to transform patient outcomes. In a patient who is not responding to conventional therapy with inhaled corticosteroids and long-acting β2-agonists, it is important to first consider if the diagnosis of asthma is correct and, second, to reflect on whether readily modifiable factors are contributing to poor asthma control. In selected patients it may be appropriate to consider a modified n-of-1 trial of add-on therapies such as long-acting anti-muscarinic agents, leukotriene blockers, theophylline or low dose macrolide antibiotics. A number of monoclonal antibodies are now available that target the molecular pathways that contribute to asthma pathogenesis, and more such agents are likely to emerge in the near future. These biologicals can be transformative in selected patients, markedly reducing the frequency of asthma exacerbations, and allowing many patients to reduce or eliminate their use of long term oral corticosteroids. If the promise of personalised treatment is to be fully realised, it is important that better methods are developed to target these new and expensive treatments to patients most likely to respond. The ultimate goal of inducing remission or cure of asthma is still some distance away. [ABSTRACT FROM AUTHOR]

Background: Better population data on respiratory viruses in children in tropical and southern hemisphere countries is needed.Methods: The epidemiology of respiratory viruses among healthy children (6 months to <10 years) with influenza-like illness (ILI) was determined in a population sample derived from an influenza vaccine trial (NCT01051661) in 17 centers in eight countries (Australia, South East Asia and Latin America). Active surveillance for ILI was conducted for approximately 1 year (between February 2010 and August 2011), with PCR analysis of nasal and throat swabs.Results: 6266 children were included, of whom 2421 experienced 3717 ILI episodes. Rhinovirus/enterovirus had the highest prevalence (41.5%), followed by influenza (15.8%), adenovirus (9.8%), parainfluenza and respiratory syncytial virus (RSV) (both 9.7%), coronavirus (5.6%), human metapneumovirus (5.5%) and human bocavirus (HBov) (2.0%). Corresponding incidence per 100 person-years was 29.78, 11.34, 7.03, 6.96, 6.94, 4.00, 3.98 and 1.41. Except for influenza, respiratory virus prevalence declined with age. The incidence of medically-attended ILI associated with viral infection ranged from 1.03 (HBov) to 23.69 (rhinovirus/enterovirus). The percentage of children missing school or daycare ranged from 21.4% (HBov) to 52.1% (influenza).Conclusions: Active surveillance of healthy children provided evidence of respiratory illness burden associated with several viruses, with a substantial burden in older children. [ABSTRACT FROM AUTHOR]

Background and purpose: Physical inactivity and prolonged sitting have associations with adverse health. University office workers are at a high risk of psychological and pain issues. This study aimed to explore the differences in sitting time, levels of physical activity participation, stress, depression, anxiety, and pain among university office workers in China and Australia. Methods: Online surveys were distributed to university office workers over 55 years at two universities in China and Australia, respectively. Results: A total of 185 participants completed the online survey (119 in China and 66 in Australia). Significant differences were found in sitting time during workdays between the two countries (p < 0.05) with a longer sitting time in the Australian respondents (7.5 h/day) than those in China (4.6 h/day). Additionally, there were also significant differences in terms of levels of depression and pain symptoms within the two countries (p < 0.05). The Australian respondents reported high levels of depression and pain (M = 7.38, SD = 5.86 and M = 3.65, SD = 2.21, respectively) than those in China (M = 5.71, SD = 4.87 and M = 1.89, SD = 1.89, respectively). The gender, education level, and sitting time of participants were found to be associated with pain scores (p < 0.05). A significant association between marital status and pain scores was found among the Australian respondents (p < 0.05). Conclusions: Future studies with a larger population are needed to validate the results and to further explore the association between physical activity participation and psychological wellbeing among university office workers. [ABSTRACT FROM AUTHOR]

Background: As part of the accelerated development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we report a dose-finding and adjuvant justification study of SCB-2019, a protein subunit vaccine candidate containing a stabilised trimeric form of the spike (S)-protein (S-Trimer) combined with two different adjuvants.Methods: Our study is a phase 1, randomised, double-blind placebo-controlled trial at a specialised clinical trials centre in Australia. We enrolled healthy adult volunteers in two age groups: younger adults (aged 18-54 years) and older adults (aged 55-75 years). Participants were randomly allocated either vaccine or placebo using a list prepared by the study funder. Participants were to receive two doses of SCB-2019 (either 3 μg, 9 μg, or 30 μg) or a placebo (0·9% NaCl) 21 days apart. SCB-2019 either had no adjuvant (S-Trimer protein alone) or was adjuvanted with AS03 or CpG/Alum. The assigned treatment was administered in opaque syringes to maintain masking of assignments. Reactogenicity was assessed for 7 days after each vaccination. Humoral responses were measured as SCB-2019 binding IgG antibodies and ACE2-competitive blocking IgG antibodies by ELISA and as neutralising antibodies by wild-type SARS-CoV-2 microneutralisation assay. Cellular responses to pooled S-protein peptides were measured by flow-cytometric intracellular cytokine staining. This trial is registered with ClinicalTrials.gov, NCT04405908; this is an interim analysis and the study is continuing.Findings: Between June 19 and Sept 23, 2020, 151 volunteers were enrolled; three people withdrew, two for personal reasons and one with an unrelated serious adverse event (pituitary adenoma). 148 participants had at least 4 weeks of follow-up after dose two and were included in this analysis (database lock, Oct 23, 2020). Vaccination was well tolerated, with two grade 3 solicited adverse events (pain in 9 μg AS03-adjuvanted and 9 μg CpG/Alum-adjuvanted groups). Most local adverse events were mild injection-site pain, and local events were more frequent with SCB-2019 formulations containing AS03 adjuvant (44-69%) than with those containing CpG/Alum adjuvant (6-44%) or no adjuvant (3-13%). Systemic adverse events were more frequent in younger adults (38%) than in older adults (17%) after the first dose but increased to similar levels in both age groups after the second dose (30% in older and 34% in younger adults). SCB-2019 with no adjuvant elicited minimal immune responses (three seroconversions by day 50), but SCB-2019 with fixed doses of either AS03 or CpG/Alum adjuvants induced high titres and seroconversion rates of binding and neutralising antibodies in both younger and older adults (anti-SCB-2019 IgG antibody geometric mean titres at day 36 were 1567-4452 with AS03 and 174-2440 with CpG/Alum). Titres in all AS03 dose groups and the CpG/Alum 30 μg group were higher than were those recorded in a panel of convalescent serum samples from patients with COVID-19. Both adjuvanted SCB-2019 formulations elicited T-helper-1-biased CD4+ T-cell responses.Interpretation: The SCB-2019 vaccine, comprising S-Trimer protein formulated with either AS03 or CpG/Alum adjuvants, elicited robust humoral and cellular immune responses against SARS-CoV-2, with high viral neutralising activity. Both adjuvanted vaccine formulations were well tolerated and are suitable for further clinical development.Funding: Clover Biopharmaceuticals and the Coalition for Epidemic Preparedness Innovations. [ABSTRACT FROM AUTHOR]

Background: Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma remission., Methods: This observational study included 453 severe asthma patients (41% male; mean age ± SD 55.7 ± 14.7 years) from two real-world drug registries: the Australian Mepolizumab Registry and the Australian Xolair Registry. The composite outcome clinical remission was defined as zero exacerbations and zero oral corticosteroids during the previous 6 months assessed at 12 months and 5-item Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. We also assessed clinical remission plus optimization (post-bronchodilator FEV1 ≥80%) or stabilization (post-bronchodilator FEV1 not greater than 5% decline from baseline) of lung function at 12 months. Sensitivity analyses explored various cut-offs of ACQ-5/FEV1 scores. The predictors of clinical remission were identified., Results: 29.3% (73/249) of AMR and 22.8% (37/162) of AXR cohort met the criteria for clinical remission. When lung function criteria were added, the remission rates were reduced to 25.2% and 19.1%, respectively. Sensitivity analyses identified that the remission rate ranged between 18.1% and 34.9% in the AMR cohort and 10.6% and 27.2% in the AXR cohort. Better lung function, lower body mass index, mild disease and absence of comorbidities such as obesity, depression and osteoporosis predicted the odds of achieving clinical remission., Conclusion: Biologic treatment with mepolizumab or omalizumab for severe asthma-induced asthma remission in a subgroup of patients. Remission on treatment may be an achievable treatment target and future studies should consider remission as an outcome measure., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purpose: To explore the benefits of a recorded maternal voice intervention on weight, recumbent length, head circumference, and heart rate of preterm infants in the neonatal intensive care unit., Methods: A pilot randomised controlled trial was conducted in this study. Preterm infants in the neonatal intensive care unit (N = 109) were recruited and randomly assigned to an intervention or control group. Both groups received routine nursing care, while preterm infants in the intervention group received a recorded maternal voice program of 20 min, twice daily for 21 days. Preterm infants' daily weight, recumbent length, head circumference, and heart rate were collected during the 21-day intervention. Participants' heart rate in the intervention group was also recorded once a day pre-during-after the recorded maternal voice program., Results: Preterm infants in the intervention group showed a significant increase in weight (-75.94, 95% CI -108.04, -43.85, P < 0.001), recumbent length (-0.54, 95% CI -0.76, -0.32, P < 0.001), and head circumference (-0.37, 95%CI -0.56, -0.18, P < 0.001) compared with the control group. Preterm infants in the intervention group also showed significant changes in heart rate pre-during-after the recorded maternal voice program. However, no significant differences were found in the heart rate scores between the two groups., Discussion: The changes in heart rate pre-during-after the intervention may help explain participants' more significant increase in weight, recumbent length, and head circumference., Practice Implications: The recorded maternal voice intervention could be incorporated into clinical practice to promote growth and development in preterm infants in the neonatal intensive care unit., Study Registration: Australian New Zealand Clinical Trials Register, https://www.anzctr.org.au/; (registration number: ACTRN12622000019707)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Oral corticosteroids (OCS) carry serious health risks. Innovative treatment options are required to reduce excessive exposure and promote OCS stewardship., Objectives: This study evaluated the trajectories of OCS exposure (prednisolone-equivalent) in patients with severe eosinophilic asthma before and after starting mepolizumab and the predictors of becoming OCS free after 6 months of mepolizumab therapy., Methods: This real-world observational study included 309 patients from the Australian Mepolizumab Registry who were followed up for 1 year (n = 225)., Results: Patients had a median age of 60 (interquartile range: 50, 68) years, and 58% were female. At baseline, 48% used maintenance OCS, 96% had ≥1 OCS burst, and 68% had received ≥1 g of OCS in the previous year. After commencing mepolizumab, only 55% of those initially on maintenance OCS remained on this treatment by 12 months. Maintenance OCS dose reduced from median 10 (5.0, 12.5) mg/day at baseline to 2 (0, 7.0) mg/day at 12 months (P < .001). Likewise, proportions of patients receiving OCS bursts in the previous year reduced from 96% at baseline to 50% at 12 months (P < .001). Overall, 137 (48%) patients required OCS (maintenance/burst) after 6 months' mepolizumab therapy. Becoming OCS free was predicted by a lower body mass index (odds ratio: 0.925; 95% confidence interval: 0.872-0.981), late-onset asthma (1.027; 1.006-1.048), a lower Asthma Control Test score (1.111; 0.011-1.220), and not receiving maintenance OCS therapy at baseline (0.095; 0.040-0.227)., Conclusion: Mepolizumab led to a significant and sustained reduction in OCS dependence in patients with severe eosinophilic asthma. This study supports the OCS-sparing effect of mepolizumab and highlights the pivotal role of mepolizumab in OCS stewardship initiatives., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Severe asthma is a high-burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population.The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia.Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control (median Asthma Control Questionnaire (ACQ)-5 score of 3.4), frequent exacerbations (median three courses of oral corticosteroids (OCS) in the previous 12 months), and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL -1 Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%.Mepolizumab treatment reduced exacerbations requiring OCS compared with the previous year (annualised rate ratio 0.34 (95% CI 0.29-0.41); p<0.001) and hospitalisations (rate ratio 0.46 (95% CI 0.33-0.63); p<0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline.Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting., Competing Interests: Conflict of interest: E.S. Harvey reports grants from GlaxoSmithKline that were paid to her employer, during the conduct of the study. Conflict of interest: D. Langton has received fees from GlaxoSmithKline for participation in severe asthma advisory boards. Conflict of interest: C. Katelaris reports grants from GlaxoSmithKline, during the conduct of the study; grants and personal fees for advisory board work and lectures from Sanofi, Novartis and CSL, personal fees from Seqirus and Takeda, outside the submitted work. Conflict of interest: S. Stevens has nothing to disclose. Conflict of interest: C.S. Farah reports personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Sanofi Genzyme, outside the submitted work. Conflict of interest: A. Gillman reports personal fees for advisory board work and education from GlaxoSmithKline, outside the submitted work. Conflict of interest: J. Harrington reports personal fees for education and advisory board work from AstraZeneca and GlaxoSmithKline, personal fees for education from Novartis, outside the submitted work. Conflict of interest: M. Hew reports grants and personal fees from AstraZeneca, GlaxoSmithKline and Novartis, personal fees from Sanofi, Teva and Seqirus, outside the submitted work; all paid to his institutional employer Alfred Health. Conflict of interest: V. Kritikos has nothing to disclose. Conflict of interest: N. Radhakrishna reports grants from Sanofi, outside the submitted work. Conflict of interest: P. Bardin reports per patient trial participation fees from Monash Lung and Sleep, during the conduct of the study; personal fees for advisory board work from Philip Bardin, outside the submitted work. Conflict of interest: M. Peters reports personal fees for advisory board work from Sanofi Genzyme, Novartis Pharmaceuticals and AstraZeneca, outside the submitted work. Conflict of interest: P.N. Reynolds reports grants from GlaxoSmithKline and AstraZeneca, during the conduct of the study. Conflict of interest: J.W. Upham reports grants and personal fees from AstraZeneca and GlaxoSmithKline, personal fees from Novartis and Boehringer Ingelheim, outside the submitted work. Conflict of interest: M. Baraket has nothing to disclose. Conflict of interest: S. Bowler reports personal fees for advisory board work from GlaxoSmithKline, outside the submitted work. Conflict of interest: J. Bowden reports personal fees for advisory board work from GlaxoSmithKline, AstraZeneca and Novartis, outside the submitted work. Conflict of interest: J. Chien reports personal fees from GlaxoSmithKline, outside the submitted work. Conflict of interest: L.P. Chung has nothing to disclose. Conflict of interest: C. Grainge reports personal fees from Boehringer Ingelheim, Roche Pharmaceuticals and GlaxoSmithKline, outside the submitted work. Conflict of interest: C. Jenkins reports personal fees for advisory board work, conducting meetings and developing educational content, and non-financial support from AstraZeneca, personal fees for advisory board work from Boehringer Ingleheim, grants and personal fees for advisory board work from GlaxoSmithKline, personal fees for advisory board work, facilitating symposia and developing educational content from Novartis, outside the submitted work. Conflict of interest: G.P. Katsoulotos has nothing to disclose. Conflict of interest: J. Lee reports personal fees for lectures from Boehringer Ingelheim and AstraZeneca, personal fees for consultancy from GlaxoSmithKline, outside the submitted work. Conflict of interest: V.M. McDonald reports grants and personal fees from GlaxoSmithKline, AstraZeneca and Menarini, outside the submitted work. Conflict of interest: H.K. Reddel reports grants from GlaxoSmithKline, during the conduct of the study; grants and personal fees for data monitoring committee work, advisory board work, providing independent medical education and consultancy from AstraZeneca, grants, personal fees for data monitoring committee work, advisory board work, providing independent medical education and consultancy and non-financial support (study medication) from GlaxoSmithKline, personal fees for data monitoring committee work from Merck, grants and personal fees for data monitoring committee work, advisory board work and providing independent medical education from Novartis, personal fees for providing independent medical education from Teva and Mundipharma, personal fees for advisory board work and providing independent medical education from Boehringer Ingelheim, personal fees for advisory board work from Sanofi Genzyme, outside the submitted work. Conflict of interest: J. Rimmer has nothing to disclose. Conflict of interest: P.A.B. Wark has nothing to disclose. Conflict of interest: P.G. Gibson reports grants from GlaxoSmithKline, during the conduct of the study; personal fees for lectures from AstraZeneca, GlaxoSmithKline and Novartis, grants from AstraZeneca and GlaxoSmithKline, outside the submitted work., (Copyright ©ERS 2020.)

Species of Heimioporus (Boletaceae, Boletales) in China are investigated on the basis of morphology and molecular phylogenetic analyses of DNA sequences from the nuc rDNA internal transcribed spacer ITS1-5.8S-ITS2 region and nuc 28S rDNA D1-D2 domains (28S) and translation elongation factor 1-α gene (TEF1). Three species are recognized in China: H. conicus, sp. nov., H. gaojiaocong, sp. nov., and the previously described H. japonicus. Heimioporus xerampelinus, originally described from southwestern China, is synonymized with H. japonicus; specimens from China previously regarded as H. retisporus and H. subretisporus are confirmed to represent H. japonicus and H. gaojiaocong, respectively. A key to the Chinese taxa of the genus is provided. A preliminary biogeographical analysis shows that Heimioporus in East Asia and Southeast Asia/Australia are closely related. Heimioporus japonicus is a geographically widespread species occurring in East Asia and Southeast Asia; however, no taxa common to East Asia and Australia were uncovered.

Comparative genomic analyses among closely related species can greatly enhance our understanding of plant gene and genome evolution. We report de novo-assembled AA-genome sequences for Oryza nivara, Oryza glaberrima, Oryza barthii, Oryza glumaepatula, and Oryza meridionalis. Our analyses reveal massive levels of genomic structural variation, including segmental duplication and rapid gene family turnover, with particularly high instability in defense-related genes. We show, on a genomic scale, how lineage-specific expansion or contraction of gene families has led to their morphological and reproductive diversification, thus enlightening the evolutionary process of speciation and adaptation. Despite strong purifying selective pressures on most Oryza genes, we documented a large number of positively selected genes, especially those genes involved in flower development, reproduction, and resistance-related processes. These diversifying genes are expected to have played key roles in adaptations to their ecological niches in Asia, South America, Africa and Australia. Extensive variation in noncoding RNA gene numbers, function enrichment, and rates of sequence divergence might also help account for the different genetic adaptations of these rice species. Collectively, these resources provide new opportunities for evolutionary genomics, numerous insights into recent speciation, a valuable database of functional variation for crop improvement, and tools for efficient conservation of wild rice germplasm.