Interactions between arbuscular mycorrhizal fungi and intraspecific competition affect size and size inequality of Plantago lanceolata L.

Intraspecific competition causes decreases in plant size and increases in size inequality. Arbuscular mycorrhizas usually increase the size and inequality of non-competing plants, but mycorrhizal effects often disappear when plants begin competing. We hypothesized that mycorrhizal effects on size inequality would be determined by the experimental conditions, and conducted simultaneous field and glasshouse experiments to investigate how AM fungi and intraspecific competition determine size inequality in Plantago lanceolata. 2 As predicted, plant size was reduced when plants were competing, in both field and controlled conditions. However, size inequality was unexpectedly reduced by competition. Plants may have competed in a symmetric fashion, probably for nutrients, rather than the more common situation, in which plant competition is strongly asymmetric. 3 Mycorrhizas had no effect on plant size or size inequality in competing plants in either field or controlled conditions, possibly because competition for nutrients was intense and negated any benefit the fungi could provide. 4 The effects of mycorrhizas on non-competing plants were also unexpected. In field-grown plants, AM fungi increased plant size, but decreased size inequality: mycorrhizal plants were more even in size, with few very small individuals. In glasshouse conditions, mycorrhizal colonization was extremely high, and was generally antagonistic, causing a reduction in plant size. Here, however, mycorrhizas caused an increase in size inequality, supporting our original hypothesis. This was because most plants were heavily colonized and small, but a few had low levels of colonization and grew relatively large. 5 This study has important implications for understanding the forces that structure plant communities. AM fungi can have a variety of effects on size inequality and thus potentially important influences on long-term plant population dynamics, by affecting the genetic contribution of individuals to the next generation. However, these effects differ, depending on whether plants are competing or not, the degree of mycorrhizal colonization and the responsiveness of the plant to different colonization densities

Nebulized Recombinant Tissue Plasminogen Activator (rt-PA) for Acute COVID-19-Induced Respiratory Failure: An Exploratory Proof-of-Concept Trial

Acute lung injury in COVID-19 results in diffuse alveolar damage with disruption of the alveolar-capillary barrier, coagulation activation, alveolar fibrin deposition and pulmonary capillary thrombi. Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to facilitate localized thrombolysis in the alveolar compartment and improve oxygenation. In this proof-of-concept safety study, adults with COVID-19-induced respiratory failure and a <300 mmHg PaO2/FiO2 (P/F) ratio requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care, between 23 April–30 July 2020 and 21 January–19 February 2021, respectively. Matched historical controls (MHC; n = 18) were used in C1 to explore efficacy. Safety co-primary endpoints were treatment-related bleeds and <1.0–1.5 g/L fibrinogen reduction. A variable dosing strategy with clinical efficacy endpoint and minimal safety concerns was determined in C1 for use in C2; patients were stratified by ventilation type to receive 40–60 mg rt-PA daily for ≤14 days. Nine patients in C1 (IMV, 6/9; NIRS, 3/9) and 26 in C2 (IMV, 12/26; NIRS, 14/26) received nebulized rt-PA for a mean (SD) of 6.7 (4.6) and 9.1(4.6) days, respectively. Four bleeds (one severe, three mild) in three patients were considered treatment related. There were no significant fibrinogen reductions. Greater improvements in mean P/F ratio from baseline to study end were observed in C1 compared with MHC (C1; 154 to 299 vs. MHC; 154 to 212). In C2, there was no difference in the baseline P/F ratio of NIRS and IMV patients. However, a larger improvement in the P/F ratio occurred in NIRS patients (NIRS; 126 to 240 vs. IMV; 120 to 188) and fewer treatment days were required (NIRS; 7.86 vs. IMV; 10.5). Nebulized rt-PA appears to be well-tolerated, with a trend towards improved oxygenation, particularly in the NIRS group. Randomized clinical trials are required to demonstrate the clinical effect significance and magnitude