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  1. Wu DB, Roberts CS, Huang YC, Chien L, Fang CH, Chang CJ
    J Med Econ, 2014 May;17(5):312-9.
    PMID: 24575941 DOI: 10.3111/13696998.2014.898644
    Invasive pneumococcal disease (IPD) and pneumococcal pneumonia cause substantial morbidity and mortality worldwide. This retrospective study was conducted to estimate the disease burden from pneumococcal disease in older adults in Taiwan from a health insurer's perspective.
  2. Delcourt C, Wang X, Zhou Z, Wardlaw JM, Mair G, Robinson TG, et al.
    J Neurol Neurosurg Psychiatry, 2020 12;91(12):1290-1296.
    PMID: 33055145 DOI: 10.1136/jnnp-2020-323015
    OBJECTIVE: To test the hypothesis that imaging signs of 'brain frailty' and acute ischaemia predict clinical outcomes and symptomatic intracranial haemorrhage (sICH) after thrombolysis for acute ischaemic stroke (AIS) in the alteplase dose arm of ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED).

    METHODS: Blinded assessors coded baseline images for acute ischaemic signs (presence, extent, swelling and attenuation of acute lesions; and hyperattenuated arteries) and pre-existing changes (atrophy, leucoaraiosis and old ischaemic lesions). Logistic regression models assessed associations between imaging features and death at 7 and 90 days; good recovery (modified Rankin Scale scores 0-2 at 90 days) and sICH. Data are reported with adjusted ORs and 95% CIs.

    RESULTS: 2916 patients (67±13 years, National Institutes of Health Stroke Scale 8 (5-14)) were included. Visible ischaemic lesions, severe hypoattenuation, large ischaemic lesion, swelling and hyperattenuated arteries were associated with 7-day death (OR (95% CI): 1.52 (1.06 to 2.18); 1.51 (1.01 to 2.18); 2.67 (1.52 to 4.71); 1.49 (1.03 to 2.14) and 2.17 (1.48 to 3.18)) and inversely with good outcome. Severe atrophy was inversely associated with 7-day death (0.52 (0.29 to 0.96)). Atrophy (1.52 (1.08 to 2.15)) and severe leucoaraiosis (1.74 (1.20 to 2.54)) were associated with 90-day death. Hyperattenuated arteries were associated with sICH (1.71 (1.01 to 2.89)). No imaging features modified the effect of alteplase dose.

    CONCLUSIONS: Non-expert-defined brain imaging signs of brain frailty and acute ischaemia contribute to the prognosis of thrombolysis-treated AIS patients for sICH and mortality. However, these imaging features showed no interaction with alteplase dose.

  3. Moullaali TJ, Wang X, Woodhouse LJ, Law ZK, Delcourt C, Sprigg N, et al.
    BMJ Open, 2019 Jul 16;9(7):e030121.
    PMID: 31315876 DOI: 10.1136/bmjopen-2019-030121
    INTRODUCTION: Conflicting results from multiple randomised trials indicate that the methods and effects of blood pressure (BP) reduction after acute intracerebral haemorrhage (ICH) are complex. The Blood pressure in Acute Stroke Collaboration is an international collaboration, which aims to determine the optimal management of BP after acute stroke including ICH.

    METHODS AND ANALYSIS: A systematic review will be undertaken according to the Preferred Reporting Items for Systematic review and Meta-Analysis of Individual Participant Data (IPD) guideline. A search of Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE from inception will be conducted to identify randomised controlled trials of BP management in adults with acute spontaneous (non-traumatic) ICH enrolled within the first 7 days of symptom onset. Authors of studies that meet the inclusion criteria will be invited to share their IPD. The primary outcome will be functional outcome according to the modified Rankin Scale. Safety outcomes will be early neurological deterioration, symptomatic hypotension and serious adverse events. Secondary outcomes will include death and neuroradiological and haemodynamic variables. Meta-analyses of pooled IPD using the intention-to-treat dataset of included trials, including subgroup analyses to assess modification of the effects of BP lowering by time to treatment, treatment strategy and patient's demographic, clinical and prestroke neuroradiological characteristics.

    ETHICS AND DISSEMINATION: No new patient data will be collected nor is there any deviation from the original purposes of each study where ethical approvals were granted; therefore, further ethical approval is not required. Results will be reported in international peer-reviewed journals.

    PROSPERO REGISTRATION NUMBER: CRD42019141136.

  4. Kelly AM, Keijzers G, Klim S, Graham CA, Craig S, Kuan WS, et al.
    Emerg Med Australas, 2015 Jun;27(3):187-91.
    PMID: 25940885 DOI: 10.1111/1742-6723.12397
    Shortness of breath is a common reason for ED attendance. This international study aims to describe the epidemiology of dyspnoea presenting to EDs in the South East Asia-Pacific region, to compare disease patterns across regions, to understand how conditions are investigated and treated, and to assess quality of care.
  5. Kelly AM, Keijzers G, Klim S, Craig S, Kuan WS, Holdgate A, et al.
    Age Ageing, 2021 01 08;50(1):252-257.
    PMID: 32997140 DOI: 10.1093/ageing/afaa121
    OBJECTIVES: To describe the epidemiology and outcomes of non-traumatic dyspnoea in patients aged 75 years or older presenting to emergency departments (EDs) in the Asia-Pacific region.

    METHODS: A substudy of a prospective interrupted time series cohort study conducted at three time points in EDs in Australia, New Zealand, Singapore, Hong Kong and Malaysia of patients presenting to the ED with dyspnoea as a main symptom. Data were collected over three 72-h periods and included demographics, co-morbidities, mode of arrival, usual medications, ED investigations and treatment, ED diagnosis and disposition, and outcome. The primary outcomes of interest are the epidemiology and outcome of patients aged 75 years or older presenting to the ED with dyspnoea.

    RESULTS: 1097 patients were included. Older patients with dyspnoea made up 1.8% [95% confidence interval (CI) 1.7-1.9%] of ED presentations. The most common diagnoses were heart failure (25.3%), lower respiratory tract infection (25.2%) and chronic obstructive pulmonary disease (17.6%). Hospital ward admission was required for 82.6% (95% CI 80.2-84.7%), with 2.5% (95% CI 1.7-3.6%) requiring intensive care unit (ICU) admission. In-hospital mortality was 7.9% (95% CI 6.3-9.7%). Median length of stay was 5 days (interquartile range 2-8 days).

    CONCLUSION: Older patients with dyspnoea make up a significant proportion of ED case load, and have a high admission rate and significant mortality. Exacerbations or worsening of pre-existing chronic disease account for a large proportion of cases which may be amenable to improved chronic disease management.

  6. Kelly AM, Keijzers G, Klim S, Graham CA, Craig S, Kuan WS, et al.
    Acad Emerg Med, 2017 Mar;24(3):328-336.
    PMID: 27743490 DOI: 10.1111/acem.13118
    OBJECTIVES: The objective was to describe the epidemiology of dyspnea presenting to emergency departments (EDs) in the Asia-Pacific region, to understand how it is investigated and treated and its outcome.

    METHODS: Prospective interrupted time series cohort study conducted at three time points in EDs in Australia, New Zealand, Singapore, Hong Kong, and Malaysia of adult patients presenting to the ED with dyspnea as a main symptom. Data were collected over three 72-hour periods and included demographics, comorbidities, mode of arrival, usual medications, prehospital treatment, initial assessment, ED investigations, treatment in the ED, ED diagnosis, disposition from ED, in-hospital outcome, and final hospital diagnosis. The primary outcomes of interest are the epidemiology, investigation, treatment, and outcome of patients presenting to ED with dyspnea.

    RESULTS: A total of 3,044 patients were studied. Patients with dyspnea made up 5.2% (3,105/60,059, 95% confidence interval [CI] = 5.0% to 5.4%) of ED presentations, 11.4% of ward admissions (1,956/17,184, 95% CI = 10.9% to 11.9%), and 19.9% of intensive care unit (ICU) admissions (104/523, 95% CI = 16.7% to 23.5%). The most common diagnoses were lower respiratory tract infection (20.2%), heart failure (14.9%), chronic obstructive pulmonary disease (13.6%), and asthma (12.7%). Hospital ward admission was required for 64% of patients (95% CI = 62% to 66%) with 3.3% (95% CI = 2.8% to 4.1%) requiring ICU admission. In-hospital mortality was 6% (95% CI = 5.0% to 7.2%).

    CONCLUSION: Dyspnea is a common symptom in ED patients contributing substantially to ED, hospital, and ICU workload. It is also associated with significant mortality. There are a wide variety of causes however chronic disease accounts for a large proportion.

  7. Keijzers G, Kelly AM, Cullen L, Klim S, Graham CA, Craig S, et al.
    BMJ Open, 2017 02 28;7(2):e013812.
    PMID: 28246137 DOI: 10.1136/bmjopen-2016-013812
    OBJECTIVES: To describe demographic features, assessment, management and outcomes of patients who were diagnosed with heart failure after presenting to an emergency department (ED) with a principal symptom of dyspnoea.

    DESIGN: Planned substudy of the prospective, descriptive cohort study: Asia, Australia and New Zealand Dyspnoea in Emergency Departments (AANZDEM).

    SETTING: 46 EDs in Australia, New Zealand, Singapore, Hong Kong and Malaysia collected data over 3 72-hour periods in May, August and October 2014.

    PARTICIPANTS: Patients with an ED diagnosis of heart failure.

    OUTCOME MEASURES: Outcomes included patient epidemiology, investigations ordered, treatment modalities used and patient outcomes (hospital length of stay (LOS) and mortality).

    RESULTS: 455 (14.9%) of the 3044 patients had an ED diagnosis of heart failure. Median age was 79 years, half were male and 62% arrived via ambulance. 392 (86%) patients were admitted to hospital. ED diagnosis was concordant with hospital discharge diagnosis in 81% of cases. Median hospital LOS was 6 days (IQR 4-9) and in-hospital mortality was 5.1%. Natriuretic peptide levels were ordered in 19%, with lung ultrasound (<1%) and echocardiography (2%) uncommonly performed. Treatment modalities included non-invasive ventilation (12%), diuretics (73%), nitrates (25%), antibiotics (16%), inhaled β-agonists (13%) and corticosteroids (6%).

    CONCLUSIONS: In the Asia Pacific region, heart failure is a common diagnosis among patients presenting to the ED with a principal symptom of dyspnoea. Admission rates were high and ED diagnostic accuracy was good. Despite the seemingly suboptimal adherence to investigation and treatment guidelines, patient outcomes were favourable compared with other registries.

  8. Kuan WS, Craig S, Kelly AM, Keijzers G, Klim S, Graham CA, et al.
    Clin Respir J, 2018 Jun;12(6):2117-2125.
    PMID: 29469993 DOI: 10.1111/crj.12782
    INTRODUCTION: Shortness of breath is a common presenting symptom to the emergency department (ED) that can arise from a myriad of possible diagnoses. Asthma is one of the major causes.

    OBJECTIVE: The aim of this study was to describe the demographic features, clinical characteristics, management and outcomes of adults with an ED diagnosis of asthma who presented to an ED in the Asia Pacific region with a principal symptom of dyspnea.

    METHODS: Planned sub-study of patients with an ED diagnosis of asthma identified in the Asia, Australia and New Zealand Dyspnoea in Emergency Departments (AANZDEM) study. AANZDEM was a prospective cohort study conducted in 46 EDs in Australia, New Zealand, Singapore, Hong Kong and Malaysia over three 72 hour periods in May, August and October 2014. Primary outcomes were patient epidemiology, clinical features, treatment and outcomes (hospital length of stay (LOS) and mortality).

    RESULTS: Of the 3044 patients with dyspnea, 387 (12.7%) patients had an ED diagnosis of asthma. The median age was 45 years, 60.1% were female, 16.1% were active or recent smokers and 30.4% arrived by ambulance. Inhaled bronchodilator therapy was initiated in 88.1% of patients, and 66.9% received both inhaled bronchodilators and systemic corticosteroids. After treatment in the ED, 65.4% were discharged. No death was reported.

    CONCLUSION: Asthma is common among patients presenting with a principal symptom of dyspnea in the ED of the Asia Pacific region. There was a suboptimal adherence to international guidelines on investigations and treatments of acute asthma exacerbations presenting an opportunity to improve the efficiency of care.

  9. Kelly AM, Holdgate A, Keijzers G, Klim S, Graham CA, Craig S, et al.
    Respirology, 2018 07;23(7):681-686.
    PMID: 29394524 DOI: 10.1111/resp.13259
    BACKGROUND AND OBJECTIVE: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common presentation to emergency departments (ED) but data regarding its epidemiology and outcomes are scarce. We describe the epidemiology, clinical features, treatment and outcome of patients treated for AECOPD in ED.

    METHODS: This was a planned sub-study of patients with an ED diagnosis of AECOPD identified in the Asia, Australia and New Zealand Dyspnoea in Emergency Departments (AANZDEM) study. The AANZDEM was a prospective, interrupted time series cohort study conducted in 46 ED in Australia, New Zealand, Singapore, Hong Kong and Malaysia over three 72-h periods in May, August and October 2014. Primary outcomes were patient epidemiology, clinical features, treatment and outcomes (hospital length of stay (LOS) and mortality).

    RESULTS: Forty-six ED participated. There were 415 patients with an ED primary diagnosis of AECOPD (13.6% of the overall cohort; 95% CI: 12.5-14.9%). Median age was 73 years, 60% males and 65% arrived by ambulance. Ninety-one percent had an existing COPD diagnosis. Eighty percent of patients received inhaled bronchodilators, 66% received systemic corticosteroids and 57% of those with pH < 7.30 were treated with non-invasive ventilation (NIV). Seventy-eight percent of patients were admitted to hospital, 7% to an intensive care unit. In-hospital mortality was 4% and median LOS was 4 days (95% CI: 2-7).

    CONCLUSION: Patients treated in ED for AECOPD commonly arrive by ambulance, have a high admission rate and significant in-hospital mortality. Compliance with evidence-based treatments in ED is suboptimal affording an opportunity to improve care and potentially outcomes.

  10. Slack AT, Khairani-Bejo S, Symonds ML, Dohnt MF, Galloway RL, Steigerwalt AG, et al.
    Int J Syst Evol Microbiol, 2009 Apr;59(Pt 4):705-8.
    PMID: 19329592 DOI: 10.1099/ijs.0.002766-0
    A single Leptospira strain (designated Bejo-Iso9(T)) was isolated from a soil sample taken in Johor, Malaysia. The isolate showed motility and morphology typical of the genus Leptospira under dark-field microscopy. Cells were found to be 10-13 microm in length and 0.2 microm in diameter, with a wavelength of 0.5 microm and an amplitude of approximately 0.2 microm. Phenotypically, strain Bejo-Iso9(T) grew in Ellinghausen-McCullough-Johnson-Harris medium at 13, 30 and 37 degrees C, and also in the presence of 8-azaguanine. Serologically, strain Bejo-Iso9(T) produced titres towards several members of the Tarassovi serogroup, but was found to be serologically unique by cross-agglutinin absorption test and thus represented a novel serovar. The proposed name for this serovar is Malaysia. Phylogenetic analysis of 16S rRNA gene sequences placed this novel strain within the radiation of the genus Leptospira, with sequence similarities within the range 90.4-99.5% with respect to recognized Leptospira species. DNA-DNA hybridization against the three most closely related Leptospira species was used to confirm the results of the 16S rRNA gene sequence analysis. The G+C content of the genome of strain Bejo-Iso9(T) was 36.2 mol%. On the basis of phenotypic, serological and phylogenetic data, strain Bejo-Iso9(T) represents a novel species of the genus Leptospira, for which the name Leptospira kmetyi sp. nov. is proposed. The type strain is Bejo-Iso9(T) (=WHO LT1101(T)=KIT Bejo-Iso9(T)).
  11. Moullaali TJ, Wang X, Sandset EC, Woodhouse LJ, Law ZK, Arima H, et al.
    J Neurol Neurosurg Psychiatry, 2022 01;93(1):6-13.
    PMID: 34732465 DOI: 10.1136/jnnp-2021-327195
    OBJECTIVE: To summarise evidence of the effects of blood pressure (BP)-lowering interventions after acute spontaneous intracerebral haemorrhage (ICH).

    METHODS: A prespecified systematic review of the Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE databases from inception to 23 June 2020 to identify randomised controlled trials that compared active BP-lowering agents versus placebo or intensive versus guideline BP-lowering targets for adults <7 days after ICH onset. The primary outcome was function (distribution of scores on the modified Rankin scale) 90 days after randomisation. Radiological outcomes were absolute (>6 mL) and proportional (>33%) haematoma growth at 24 hours. Meta-analysis used a one-stage approach, adjusted using generalised linear mixed models with prespecified covariables and trial as a random effect.

    RESULTS: Of 7094 studies identified, 50 trials involving 11 494 patients were eligible and 16 (32.0%) shared patient-level data from 6221 (54.1%) patients (mean age 64.2 [SD 12.9], 2266 [36.4%] females) with a median time from symptom onset to randomisation of 3.8 hours (IQR 2.6-5.3). Active/intensive BP-lowering interventions had no effect on the primary outcome compared with placebo/guideline treatment (adjusted OR for unfavourable shift in modified Rankin scale scores: 0.97, 95% CI 0.88 to 1.06; p=0.50), but there was significant heterogeneity by strategy (pinteraction=0.031) and agent (pinteraction<0.0001). Active/intensive BP-lowering interventions clearly reduced absolute (>6 ml, adjusted OR 0.75, 95%CI 0.60 to 0.92; p=0.0077) and relative (≥33%, adjusted OR 0.82, 95%CI 0.68 to 0.99; p=0.034) haematoma growth.

    INTERPRETATION: Overall, a broad range of interventions to lower BP within 7 days of ICH onset had no overall benefit on functional recovery, despite reducing bleeding. The treatment effect appeared to vary according to strategy and agent.

    PROSPERO REGISTRATION NUMBER: CRD42019141136.

  12. Anderson CS, Rodgers A, de Silva HA, Martins SO, Klijn CJ, Senanayake B, et al.
    Int J Stroke, 2022 Dec;17(10):1156-1162.
    PMID: 34994269 DOI: 10.1177/17474930211068671
    BACKGROUND: Patients who suffer intracerebral hemorrhage (ICH) are at very high risk of recurrent ICH and other serious cardiovascular events. A single-pill combination (SPC) of blood pressure (BP) lowering drugs offers a potentially powerful but simple strategy to optimize secondary prevention.

    OBJECTIVES: The Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial (TRIDENT) aims to determine the effects of a novel SPC "Triple Pill," three generic antihypertensive drugs with demonstrated efficacy and complementary mechanisms of action at half standard dose (telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg), with placebo for the prevention of recurrent stroke, cardiovascular events, and cognitive impairment after ICH.

    DESIGN: An international, double-blind, placebo-controlled, randomized trial in adults with ICH and mild-moderate hypertension (systolic BP: 130-160 mmHg), who are not taking any Triple Pill component drug at greater than half-dose. A total of 1500 randomized patients provide 90% power to detect a hazard ratio of 0.5, over an average follow-up of 3 years, according to a total primary event rate (any stroke) of 12% in the control arm and other assumptions. Secondary outcomes include recurrent ICH, cardiovascular events, and safety.

    RESULTS: Recruitment started 28 September 2017. Up to 31 October 2021, 821 patients were randomized at 54 active sites in 10 countries. Triple Pill adherence after 30 months is 86%. The required sample size should be achieved by 2024.

    CONCLUSION: Low-dose Triple Pill BP lowering could improve long-term outcome from ICH.

  13. Ouyang M, Faigle R, Wang X, Johnson B, Summers D, Khatri P, et al.
    Cerebrovasc Dis, 2023 Oct 26.
    PMID: 37883934 DOI: 10.1159/000534706
    Introduction Careful monitoring of patients who receive intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is resource-intensive, and potentially less relevant in those with mild degrees of neurological impairment who are at low-risk of symptomatic intracerebral hemorrhage (sICH) and other complications. \ Methods OPTIMISTmain is an international, multicenter, prospective, stepped wedge, cluster randomized, blinded outcome assessed trial aims to determine whether a less-intensity monitoring protocol is at least as effective, safe and efficient as standard post-IVT monitoring in patients with mild deficits post-AIS. Clinically-stable adult patients with mild AIS (defined by a NIHSS <10) who do not require intensive care within 2 hours post-IVT are recruited at hospitals in Australia, Chile, China, Malaysia, Mexico, UK, US and Vietnam. An average of 15 patients recruited per period (overall 60 patient participants) at 120 sites for a total of 7200 IVT-treated AIS patients will provide 90% power (one-sided α 0.025). The initiation of eligible hospitals is based on a rolling process whenever ready, stratified by country. Hospitals are randomly allocated using permuted blocks into 3 sequences of implementation, stratified by country and the projected number of patients to be recruited over 12 months. These sequences have four periods that dictate the order in which they are to switch from control (usual care) to intervention (implementation of low intensity monitoring protocol) to different clusters of patients in a stepped manner. Compared to standard monitoring, the low-intensity monitoring protocol includes assessments of neurological and vital signs every 15 minutes for 2 hours, 2 hourly (versus every 30 minutes) for 8 hours, and 4 hourly (versus every 1 hour) until 24 hours, post-IVT. The primary outcome measure is functional recovery, defined by the modified Rankin scale (mRS) at 90 days, a seven-point ordinal scale (0 [no residual symptom] to 6 [death]). Secondary outcomes include death or dependency, length of hospital stay, and health-related quality of life, sICH and serious adverse events. Conclusion OPTIMISTmain will provide Level I evidence for the safety and effectiveness of a low-intensity post-IVT monitoring protocol in patients with mild severity of AIS.
  14. Wang X, Yang J, Moullaali TJ, Sandset EC, Woodhouse LJ, Law ZK, et al.
    Stroke, 2024 Apr;55(4):849-855.
    PMID: 38410986 DOI: 10.1161/STROKEAHA.123.044358
    OBJECTIVE: To investigate whether an earlier time to achieving and maintaining systolic blood pressure (SBP) at 120 to 140 mm Hg is associated with favorable outcomes in a cohort of patients with acute intracerebral hemorrhage.

    METHODS: We pooled individual patient data from randomized controlled trials registered in the Blood Pressure in Acute Stroke Collaboration. Time was defined as time form symptom onset plus the time (hour) to first achieve and subsequently maintain SBP at 120 to 140 mm Hg over 24 hours. The primary outcome was functional status measured by the modified Rankin Scale at 90 to 180 days. A generalized linear mixed models was used, with adjustment for covariables and trial as a random effect.

    RESULTS: A total of 5761 patients (mean age, 64.0 [SD, 13.0], 2120 [36.8%] females) were included in analyses. Earlier SBP control was associated with better functional outcomes (modified Rankin Scale score, 3-6; odds ratio, 0.98 [95% CI, 0.97-0.99]) and a significant lower risk of hematoma expansion (0.98, 0.96-1.00). This association was stronger in patients with bigger baseline hematoma volume (>10 mL) compared with those with baseline hematoma volume ≤10 mL (0.006 for interaction). Earlier SBP control was not associated with cardiac or renal adverse events.

    CONCLUSIONS: Our study confirms a clear time relation between early versus later SBP control (120-140 mm Hg) and outcomes in the one-third of patients with intracerebral hemorrhage who attained sustained SBP levels within this range. These data provide further support for the value of early recognition, rapid transport, and prompt initiation of treatment of patients with intracerebral hemorrhage.

  15. Battlay P, Wilson J, Bieker VC, Lee C, Prapas D, Petersen B, et al.
    Nat Commun, 2023 Mar 27;14(1):1717.
    PMID: 36973251 DOI: 10.1038/s41467-023-37303-4
    Adaptation is the central feature and leading explanation for the evolutionary diversification of life. Adaptation is also notoriously difficult to study in nature, owing to its complexity and logistically prohibitive timescale. Here, we leverage extensive contemporary and historical collections of Ambrosia artemisiifolia-an aggressively invasive weed and primary cause of pollen-induced hayfever-to track the phenotypic and genetic causes of recent local adaptation across its native and invasive ranges in North America and Europe, respectively. Large haploblocks-indicative of chromosomal inversions-contain a disproportionate share (26%) of genomic regions conferring parallel adaptation to local climates between ranges, are associated with rapidly adapting traits, and exhibit dramatic frequency shifts over space and time. These results highlight the importance of large-effect standing variants in rapid adaptation, which have been critical to A. artemisiifolia's global spread across vast climatic gradients.
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