Environment, community & the individual; characterising the ecology of aquatic invasive alien plants in Ireland

The Irish freshwater environment is particularly vulnerable to invasion by alien species. Given the importance of invasive alien species as drivers and passengers of ecological change it is pertinent that the mechanisms and processes involved in the invasion of Irish aquatic habitats are better understood. The overarching aim of this research was to characterise the relevant traits, of the environment, biological communities and individuals, responsible for the successful dispersal, establishment and spread of alien macrophytes. To that end, invasive alien macrophyte species (including Elodea canadensis, Elodea nuttallii, Lagarosiphon major and Myriophyllum aquaticum) were studied in situ and ex situ, combining field surveys, comparative experiments and molecular techniques. Hypotheses relating to propagule pressure, habitat disturbance, resource availability, community invasibility, stress tolerance and cryptic invasions were tested. It was found that the occurrence and distribution of invasive alien species in standing waterbodies in Ireland is substantially greater than previously recorded. 54% of surveyed waterbodies were found to be invaded. The intensity of human amenity use was the best predictor of the occurrence of invasive alien species and there was a positive association between nutrient concentrations and the occurrence and abundance of some invasive species. The influence of alien species was additive to the native community, increasing the complexity of native assemblages in terms of richness, biomass, diversity and function of invaded ecosystems. It was found that those native species that were excluded by alien species tended to be morphologically similar. Most invasive species studied had high capacity to tolerate fragmentation and desiccation indicating their capacity to overcome barriers to reproduction, dispersal and colonization. Using a combination of lab and field based experiments, M. aquaticum was shown to utilise phenotypic plasticity in its tolerance of saline conditions, and was capable of colonising and invading brackish waters. A molecular investigation of alien Myriophyllum spp. in Ireland revealed genetic diversity amongst and between populations of the clonal species M. aquaticum. The discovery of multiple cryptic taxa (M. heterophyllum and M. sp. “red 1”) originating in the horticultural trade is of particular concern. Implications for the management of aquatic invasive species in Ireland are discussed

Saltmarshes on peat substrate on the southwest coast of Ireland: edaphic parameters and plant species distribution

Abstract. Saltmarshes on peat substrate are common along the western Atlantic coast of Ireland. The peat which underlies these marshes was formed under freshwater conditions in post glacial times, after which these systems were subjected to a marine transgression. The aim of this study was to determine the relationship between edaphic factors, substrate type and saltmarsh vegetation, specifically investigating the role of edaphic factors in determining the distribution of saltmarsh species Atriplex portulacoides in Ireland. Edaphic parameters measured for each substrate included pH, moisture content, ammonium and nitrate. The peat was found to differ markedly from other substrates. Using canonical correspondence analysis it was found that pH and ammonium were the major drivers in influencing saltmarsh vegetation on peat substrate. Under both in situ and ex situ conditions Atriplex portulacoides showed an affinity for drier substrate and its absence from fringe marshes in Ireland is likely due to a combination of both biotic and abiotic factors, including intolerance to high soil moisture levels

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

CureGN Study Rationale, Design, and Methods: Establishing a Large Prospective Observational Study of Glomerular Disease

Glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A (IgA) nephropathy, share clinical presentations, yet result from multiple biological mechanisms. Challenges to identifying underlying mechanisms, biomarkers, and new therapies include the rarity of each diagnosis and slow progression, often requiring decades to measure the effectiveness of interventions to prevent end-stage kidney disease (ESKD) or death. Multicenter prospective cohort study. Cure Glomerulonephropathy (CureGN) will enroll 2,400 children and adults with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (including IgA vasculitis) and a first diagnostic kidney biopsy within 5 years. Patients with ESKD and those with secondary causes of glomerular disease are excluded. Clinical data, including medical history, medications, family history, and patient-reported outcomes, are obtained, along with a digital archive of kidney biopsy images and blood and urine specimens at study visits aligned with clinical care 1 to 4 times per year. Patients are followed up for changes in estimated glomerular filtration rate, disease activity, ESKD, and death and for nonrenal complications of disease and treatment, including infection, malignancy, cardiovascular, and thromboembolic events. The study design supports multiple longitudinal analyses leveraging the diverse data domains of CureGN and its ancillary program. At 2,400 patients and an average of 2 years’ initial follow-up, CureGN has 80% power to detect an HR of 1.4 to 1.9 for proteinuria remission and a mean difference of 2.1 to 3.0mL/min/1.73m2 in estimated glomerular filtration rate per year. Current follow-up can only detect large differences in ESKD and death outcomes. Study infrastructure will support a broad range of scientific approaches to identify mechanistically distinct subgroups, identify accurate biomarkers of disease activity and progression, delineate disease-specific treatment targets, and inform future therapeutic trials. CureGN is expected to be among the largest prospective studies of children and adults with glomerular disease, with a broad goal to lessen disease burden and improve outcomes