Variation in mycorrhizal growth response among a spring wheat mapping population shows potential to breed for symbiotic benefit.

Funder: N8 Agrifood SchemeAll cereal crops engage in arbuscular mycorrhizal symbioses which can have profound, but sometimes deleterious, effects on plant nutrient acquisition and growth. The mechanisms underlying variable mycorrhizal responsiveness in cereals are not well characterised or understood. Adapting crops to realise mycorrhizal benefits could reduce fertiliser requirements and improve crop nutrition where fertiliser is unavailable. We conducted a phenotype screen in wheat (Triticum aestivum L.), using 99 lines of an Avalon × Cadenza doubled-haploid mapping population. Plants were grown with or without a mixed inoculum containing 5 species of arbuscular mycorrhizal fungi. Plant growth, nutrition and mycorrhizal colonisation were quantified. Plant growth response to inoculation was remarkably varied among lines, ranging from more than 30% decrease to 80% increase in shoot biomass. Mycorrhizal plants did not suffer decreasing shoot phosphorus concentration with increasing biomass as observed in their non-mycorrhizal counterparts. The extent to which mycorrhizal inoculation was beneficial for individual lines was negatively correlated with shoot biomass in the non-mycorrhizal state but was not correlated with the extent of mycorrhizal colonisation of roots. Highly variable mycorrhizal responsiveness among closely related wheat lines and the identification of several QTL for these traits suggests the potential to breed for improved crop-mycorrhizal symbiosis

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

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

Design of a Wireless Sensor Network Platform for Detecting Rare, Random, and Ephemeral Events

We present the design of the eXtreme Scale Mote, a new sensor network platform for reliably detecting and classifying, and quickly reporting, rare, random, and ephemeral events in a largescale, long-lived, and retaskable manner. This new mote was designed for the ExScal project which seeks to demonstrate a 10,000 node network capable of discriminating civilians, soldiers and vehicles, spread out over a 10km 2 area, with node lifetimes approaching 1,000 hours of continuous operation on two AA alkaline batteries. This application posed unique functional, usability, scalability, and robustness requirements which could not be met with existing hardware, and therefore motivated the design of a new platform. The detection and classification requirements are met using infrared, magnetic, and acoustic sensors. The infrared and acoustic sensors are designed for low-power continuous operation and include asynchronous processor wakeup circuitry. The usability and scalability requirements are met by minimizing the frequency and cost of human-in-the-loop operations during node deployment, activation, and verification through improvements in the user interface, packaging, and configurability of the platform. Recoverable retasking is addressed by using a grenade timer that periodically forces a system reset. The key contributions of this work are a specific design point and general design methods for building sensor network platforms to detect exceptional events. 1

Stomatal lock-up contributes to the cost of resistance to foliar fungal pathogens

Trabajo presentado en la Presidential Meeting: Fitness Costs and Trade-offs in Plant-Parasite Interactions, celebrad en Norwick (Reino Unido) del 16 al 18 de diciembre de 2012.Pathogen attack can reduce yield in plants with effective major gene resistance. In barley genotypes Pallas (susceptible) and P01 (with Mla1) attacked by Blumeria graminis f. sp. hordei (Bgh) stomacal behaviour was disrupted.Peer Reviewe

IMMU-11. SPATIOTEMPORAL IMMUNOGENOMIC ANALYSIS OF THE T-CELL REPERTOIRE IN IDH-MUTANT LOWER GRADE GLIOMAS

Abstract The design and evaluation of immunotherapies in IDH-mutant lower grade gliomas (LGG) is hindered by a poor understanding of the LGG T-cell repertoire. We present data on the temporal evolution, intratumoral spatial distribution, and prognostic value of the T-cell repertoire in IDH-mutant LGGs. We performed immunogenomic profiling using T-cell receptor beta-chain sequencing of 163 glioma and peripheral blood samples from 33 immunotherapy-naive glioma patients (22 astrocytomas, 11 oligodendrogliomas). T-cell repertoire evolution was analyzed in a subset of 26 patients (69 samples) with matched primary (WHO grade II) and recurrent (WHO grade II-IV) glioma samples. T-cell repertoire diversity was defined as the number of unique T-cell clonotypes by V-gene, J-gene, and CDR3 nucleotide sequences. Malignant transformed (Grade III or IV) recurrent gliomas demonstrated increased T-cell repertoire diversity compared to their patient-matched primary tumors (p=0.0023), but grade II recurrences did not show the same increased diversity (p=0.26). This increase in T-cell repertoire diversity was greater in patients who underwent transformation in the context of TMZ-associated hypermutation compared to spontaneously transformed counterparts (p=0.035). In grade II primary astrocytomas (n=17), T-cell repertoire diversity above the median (186 unique T-cell clonotypes per sample) was associated with worse transformation-free (HR=4.2, p=0.045) and overall survival (HR=6.4, p=0.025). Next, we evaluated intratumoral immune heterogeneity in 7 patients by sampling from up to 10 distinct and maximally-separated intratumoral sites per LGG (64 samples). Eighty-two to 96% of unique clonotypes within a given tumor were present only within a single sampled site. Despite this heterogeneity, six LGG patients harbored T-cell clonotypes present tumor-wide across all sampled sites within a given tumor. Ten of 24 (42%) tumor-wide T-cell clonotypes were enriched in the glioma compared to matched peripheral blood, suggesting glioma-specificity. Taken together, T-cell receptor profiling in LGGs may have utility both as a prognostic biomarker and to identify glioma-specific T-cells