Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Increased Activity of 5-Enolpyruvylshikimate-3-phosphate Synthase (EPSPS) Enzyme Describe the Natural Tolerance of Vulpia myuros to Glyphosate in Comparison with Apera spica-venti

Rattail fescue (Vulpia myuros (L.) C.C. Gmel.) is a self-pollinating winter annual grassy weed of winter annual crops. The problems with V. myuros are mostly associated with no-till cropping systems where glyphosate application before sowing or emergence of the crop is the most important control measure. Ineffective V. myuros control has been reported following glyphosate applications. Experiments were performed to study the effectiveness of glyphosate on V. myuros, and determine the causes of the lower performance of glyphosate on V. myuros compared to other grass weeds. Estimated GR50 values demonstrated that V. myuros was less susceptible to glyphosate than Apera spica-venti regardless of the growth stage. Within each species, glyphosate efficacy at different growth stages was closely related to spray retention. However, the low susceptibility to glyphosate in V. myuros was not caused by lower retention as previously suggested. A significantly lower shikimic acid accumulation in V. myuros compared to A. spica-venti was associated with a higher activity of the EPSPS enzyme in V. myuros. Nevertheless, the relative responses in EPSPS activity to different glyphosate concentrations were similar in the two grass species, which indicate that EPSPS from V. myuros is as susceptible to glyphosate as EPSPS from A. spica-venti suggesting no alternation in the binding site of EPSPS. The results from the current study indicate that V. myuros is less susceptible to glyphosate compared to A. spica-venti, and the low susceptibility of V. myuros is caused by an increased EPSPS enzyme activity

Low Effectiveness of Prosulfocarb and Mesosulfuron-Methyl + Iodosulfuron-Methyl against Vulpia myuros

Due to natural tolerance to most widely used herbicides for grass weed control, prosulfocarb as pre-emergence or early post-emergence herbicide and mesosulfuron + iodosulfuron as post-emergence herbicide are the mainstays of any chemical control program for Vulpia myuros in Denmark. However, farmers often report variable efficacy of these herbicides on V. myuros compared to other grass weeds. Dose–response experiments were conducted to evaluate the performance of prosulfocarb and mesosulfuron + iodosulfuron on V. myuros. Prosulfocarb was sprayed at different plant growth stages to study the influence of plant growth stage on the performance of prosulfocarb on V. myuros in comparison with the more susceptible grass weed species Apera spica-venti. Doses causing 50% reduction in response variable (ED50) were estimated from the dose–response analysis. The ED50 values revealed a higher tolerance of V. myuros to prosulfocarb and mesosulfuron + iodosulfuron than A. spica-venti. The relative difference in the effectiveness of prosulfocarb between V. myuros and A. spica-venti was constant among plant growth stages studied. The highest levels of V. myuros control were achieved when prosulfocarb was sprayed pre-emergence (BBCH 00), while the control substantially declined at later growth stages. The results from the current study document the tolerance of V. myuros to prosulfocarb and mesosulfuron + iodosulfuron and highlight the importance of optimization of prosulfocarb spray timing for achieving maximum control of V. myuros

Biology and Management of Vulpia myuros—An Emerging Weed Problem in No-Till Cropping Systems in Europe

Recently, Vulpia myuros has become a problematic grass weed species in parts of Europe. It is most common in no-till cropping systems. The inherent tolerance to several selective grass weed herbicides is of serious concern to the successful management of V. myuros in arable farming. Here, we reviewed the available knowledge about the biology of V. myuros to identify knowledge gaps and assess management efforts to identify best practices for control. V. myuros is a winter-annual species producing seeds with a short dormancy that can germinate at a wide range of conditions. Seed longevity in the soil is short. Little information is available on the influence of V. myuros on crop yield but some results suggest that yield losses can be significant. The findings provide a better understanding of the weedy characteristics of V. myuros and highlight that management strategies in Europe need to be diversified and integrate preventive and cultural control methods. Finally, we identify some of the management tools that should be considered to minimize the impact of V. myuros on European farming and future needs for research to develop sustainable integrated weed management strategies

Seed Priming with Spermine Mitigates Chromium Stress in Rice by Modifying the Ion Homeostasis, Cellular Ultrastructure and Phytohormones Balance

Chromium (Cr) is an important environmental constraint effecting crop productivity. Spermine (SPM) is a polyamine compound regulating plant responses to abiotic stresses. However, SPM-mediated tolerance mechanisms against Cr stress are less commonly explored in plants. Thus, current research was conducted to explore the protective mechanisms of SPM (0.01 mM) against Cr (100 µM) toxicity in two rice cultivars, CY927 (sensitive) and YLY689 (tolerant) at the seedling stage. Our results revealed that, alone, Cr exposure significantly reduced seed germination, biomass and photosynthetic related parameters, caused nutrient and hormonal imbalance, desynchronized antioxidant enzymes, and triggered oxidative damage by over-accretion of reactive oxygen species (ROS), malondialdehyde (MDA) and electrolyte leakage in both rice varieties, with greater impairments in CY927 than YLY689. However, seed priming with SPM notably improved or reversed the above-mentioned parameters, especially in YLY689. Besides, SPM stimulated the stress-responsive genes of endogenous phytohormones, especially salicylic acid (SA), as confirmed by the pronounced transcript levels of SA-related genes (OsPR1, OsPR2 and OsNPR1). Our findings specified that SPM enhanced rice tolerance against Cr toxicity via decreasing accumulation of Cr and markers of oxidative damage (H2O2, O2•− and MDA), improving antioxidant defense enzymes, photosynthetic apparatus, nutrients and phytohormone balance

Applications of Artificial Intelligence in Climate-Resilient Smart-Crop Breeding

Recently, Artificial intelligence (AI) has emerged as a revolutionary field, providing a great opportunity in shaping modern crop breeding, and is extensively used indoors for plant science. Advances in crop phenomics, enviromics, together with the other “omics” approaches are paving ways for elucidating the detailed complex biological mechanisms that motivate crop functions in response to environmental trepidations. These “omics” approaches have provided plant researchers with precise tools to evaluate the important agronomic traits for larger-sized germplasm at a reduced time interval in the early growth stages. However, the big data and the complex relationships within impede the understanding of the complex mechanisms behind genes driving the agronomic-trait formations. AI brings huge computational power and many new tools and strategies for future breeding. The present review will encompass how applications of AI technology, utilized for current breeding practice, assist to solve the problem in high-throughput phenotyping and gene functional analysis, and how advances in AI technologies bring new opportunities for future breeding, to make envirotyping data widely utilized in breeding. Furthermore, in the current breeding methods, linking genotype to phenotype remains a massive challenge and impedes the optimal application of high-throughput field phenotyping, genomics, and enviromics. In this review, we elaborate on how AI will be the preferred tool to increase the accuracy in high-throughput crop phenotyping, genotyping, and envirotyping data; moreover, we explore the developing approaches and challenges for multiomics big computing data integration. Therefore, the integration of AI with “omics” tools can allow rapid gene identification and eventually accelerate crop-improvement programs

Biology and management of Avena fatua and Avena ludoviciana: two noxious weed species of agro-ecosystems

Avena fatua and Avena ludoviciana are closely related grass weed species infesting a large number of crops around the world. These species are widely distributed in diverse agro-ecosystems from temperate to sub-tropical regions due to their unique seed traits, successful germination ecology, high competitive ability, and allelopathic potential. A. fatua is more widespread, adaptable, and problematic than A. ludoviciana. Both these species infest major winter and spring crops, including wheat, oat, barley, canola, maize, alfalfa, and sunflower, causing up to 70% yield losses depending on crop species and weed density. Chemical control has been challenged by large-scale herbicide resistance evolution in these weed species. A. fatua is the most widespread herbicide-resistant weed in the world, infesting about 5 million hectares in 13 countries. The use of alternative herbicides with different modes of action has proved effective. Several cultural practices, including diverse crop rotations, cover crops, improved crop competition (using competitive cultivars, high seed rates, narrow row spacing, altered crop geometry), and allelopathic suppression, have shown promise for controlling A. fatua and A. ludoviciana. The integrated use of these cultural methods can reduce the herbicide dose required, and lower dependency on herbicides to control these grasses. Moreover, integrated management may successfully control herbicide-resistant populations of these weed species. The use of integrated approaches based on the knowledge of biology and ecology of A. fatua and A. ludoviciana may help to manage them sustainably in the future