The carcass characteristics and quality of meat from lambs grazing perennial wheat with different companion legumes (clover, serradella, lucerne) or a mineral supplement.

This study compared carcasses as well as the quality and mineral concentration of meat from lambs extensively grazing perennial wheat with clover (PW + C), serradella (PW + S), lucerne (PW + L), or a mineral salt supplement (PW + Min). A split-plot design was used, wherein 3 crossbred ewe lambs (n = 72 in total) (sub-plots) grazed each of 4 forage types (plots), that were replicated across 6 locations (blocks). The feeding study concluded after 96 d, when all the lambs were slaughtered. The left longissimus lumborum muscles (LL) were collected and wet aged for either 5 or 56 d post-mortem. Lambs grazing PW + Min were found to produce carcasses with lower dressing percentage values to those grazing the other forage types (P = 0.037). The LL of lambs grazing PW + L had the lowest crude protein values (P = 0.015). Forage type by ageing period interactions did not affect meat quality. The 56 d ageing period resulted in higher purge loss (P < 0.001) and TVB-N values (P < 0.001) and a decline in shear force (P < 0.001) compared to the 5 d ageing period. The other carcass and meat quality parameters were not affected by forage type; including hot carcass weight, pH decline parameters, eye muscle area, cooking loss, intramuscular fat, sarcomere length, colour stability, and concentrations of calcium, iron, magnesium, sodium, and zinc in the LL. These findings confirm that perennial cereal production systems, that include legume forages with contrasting protein, energy, and micronutrient profiles, can deliver comparable lamb carcasses and meat quality.

Quantitative Differences in Rumen Epithelium Proteins in Lambs Fed Wheat, Perennial Wheat, or Perennial Wheat plus Lucerne.

The value of crops such as perennial wheat (PW) for grain and grazing compared to conventional wheat (W), or the addition of lucerne to PW (PWL) is still being determined. This research sought to determine if these diets were associated with changes in the membranebound proteins that transport nutrients in the rumen epithelium (RE). Crossbred ewes (Poll Dorset × Merino) were fed W, PW, or PWL (50:50) fresh-cut forage ad libitum for 4 weeks. Average daily gain (ADG; p < 0.001) was highest in the W-fed lambs compared to the PW and PWL. Metabolisable energy intake (MEI) was higher in lambs fed W (p < 0.001) compared to PW and PWL. In pairwise comparisons of the PW and PWL diet group we found protein abundance was significantly (p < 0.05, FDR < 0.05, Benjamini p < 0.05) different in fatty acid metabolism, oxidative phosphorylation, and biosynthesis of cofactors pathways. There were not any differences in protein abundance related to nutrient transport or energy metabolism in the RE between W- vs. PW- and W- vs. PWL-fed lambs. However, in the PW- vs. PWL-fed lambs, there was a difference in the level of proteins regulating the metabolism of fatty acids and energy production in the mitochondria of the rumen epithelium.

Agronomic Evaluation and Molecular Cytogenetic Characterization of Triticum aestivum × Thinopyrum spp. Derivative Breeding Lines Presenting Perennial Growth Habits.

The transition from annual to perennial growth habits can contribute to increased sustainability and diversification of staple cropping systems like those based on annual wheat. Amphiploids between Triticum aestivum and Thinopyrum spp. can present a wheat-like morphology and post sexual cycle regrowth. The complex and unpredictable nature of the chromosomal rearrangements typical of inter-generic hybrids can hamper progress in the development of this new crop. By using fluorescence in situ hybridization, we described the genomic constitution of three perennial wheat breeding lines that regrew and completed a second year of production in field conditions in Washington state (USA). Two breeding lines presented stable, 56-chromosome partial amphiploids; however, their chromosome composition differed significantly. The third breeding line presented an unstable karyotype with a chromosome number ranging from 53 to 58 across eight individuals. The agronomic performance of the perennial breeding lines was evaluated for two growing seasons from 2020 to 2022. The grain yields of the perennial lines were lower than the grain production of the annual wheat control line in the first season. The perennial lines displayed vigorous regrowth after the initial harvest; however, worsening environmental conditions in the second season of growth hampered subsequent growth and grain yield. This information facilitates the breeding work necessary to improve key traits by grouping agronomically valuable individuals according to their genomic constitution.

Pooling Different Placebos as a Control Group in a Randomized Platform Trial: Benefits and Challenges From Experience in the ACTIV-2 COVID-19 Trial.

Adaptive platform trials were implemented during the coronavirus disease 2019 (COVID-19) pandemic to rapidly evaluate therapeutics, including the placebo-controlled phase 2/3 ACTIV-2 trial, which studied 7 investigational agents with diverse routes of administration. For each agent, safety and efficacy outcomes were compared to a pooled placebo control group, which included participants who received a placebo for that agent or for other agents in concurrent evaluation. A 2-step randomization framework was implemented to facilitate this. Over the study duration, the pooled placebo design achieved a reduction in sample size of 6% versus a trial involving distinct placebo control groups for evaluating each agent. However, a 26% reduction was achieved during the period when multiple agents were in parallel phase 2 evaluation. We discuss some of the complexities implementing the pooled placebo design versus a design involving nonoverlapping control groups, with the aim of informing the design of future platform trials. Clinical Trials Registration. NCT04518410.

Discussion: Prioritize perennial grain development for sustainable food production and environmental benefits.

Perennial grains have potential to contribute to ecological intensification of food production by enabling the direct harvest of human-edible crops without requiring annual cycles of disturbance and replanting. Studies of prototype perennial grains and other herbaceous perennials point to the ability of agroecosystems including these crops to protect water quality, enhance wildlife habitat, build soil quality, and sequester soil carbon. However, genetic improvement of perennial grain candidates has been hindered by limited investment due to uncertainty about whether the approach is viable. As efforts to develop perennial grain crops have expanded in past decades, critiques of the approach have arisen. With a recent report of perennial rice producing yields equivalent to those of annual rice over eight consecutive harvests, many theoretical concerns have been alleviated. Some valid questions remain over the timeline for new crop development, but we argue these may be mitigated by implementation of recent technological advances in crop breeding and genetics such as low-cost genotyping, genomic selection, and genome editing. With aggressive research investment in the development of new perennial grain crops, they can be developed and deployed to provide atmospheric greenhouse gas reductions.

Safety and Efficacy of Combined Tixagevimab and Cilgavimab Administered Intramuscularly or Intravenously in Nonhospitalized Patients With COVID-19: 2 Randomized Clinical Trials.

Importance: Development of effective, scalable therapeutics for SARS-CoV-2 is a priority. Objective: To test the efficacy of combined tixagevimab and cilgavimab monoclonal antibodies for early COVID-19 treatment. Design, Setting, and Participants: Two phase 2 randomized blinded placebo-controlled clinical trials within the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-2/A5401 platform were performed at US ambulatory sites. Nonhospitalized adults 18 years or older within 10 days of positive SARS-CoV-2 test and symptom onset were eligible and were enrolled from February 1 to May 31, 2021. Interventions: Tixagevimab-cilgavimab, 300 mg (150 mg of each component) given intravenously (IV) or 600 mg (300 mg of each component) given intramuscularly (IM) in the lateral thigh, or pooled placebo. Main Outcomes and Measures: Coprimary outcomes were time to symptom improvement through 28 days; nasopharyngeal SARS-CoV-2 RNA below the lower limit of quantification (LLOQ) on days 3, 7, or 14; and treatment-emergent grade 3 or higher adverse events through 28 days. Results: A total of 229 participants were randomized for the IM study and 119 were randomized for the IV study. The primary modified intention-to-treat population included 223 participants who initiated IM tixagevimab-cilgavimab (n = 106) or placebo treatment (n = 117) (median age, 39 [IQR, 30-48] years; 113 [50.7%] were men) and 114 who initiated IV tixagevimab-cilgavimab (n = 58) or placebo treatment (n = 56) (median age, 44 [IQR, 35-54] years; 67 [58.8%] were women). Enrollment in the IV study was stopped early based on a decision to focus on IM product development. Participants were enrolled at a median of 6 (IQR, 4-7) days from COVID-19 symptom onset. Significant differences in time to symptom improvement were not observed for IM tixagevimab-cilgavimab vs placebo or IV tixagevimab-cilgavimab vs placebo. A greater proportion in the IM tixagevimab-cilgavimab arm (69 of 86 [80.2%]) than placebo (62 of 96 [64.6%]) had nasopharyngeal SARS-CoV-2 RNA below LLOQ at day 7 (adjusted risk ratio, 1.33 [95% CI, 1.12-1.57]) but not days 3 and 14; the joint test across time points favored treatment (P = .003). Differences in the proportion below LLOQ were not observed for IV tixagevimab-cilgavimab vs placebo at any of the specified time points. There were no safety signals with either administration route. Conclusions: In these 2 phase 2 randomized clinical trials, IM or IV tixagevimab-cilgavimab was safe but did not change time to symptom improvement. Antiviral activity was more evident in the larger IM trial. Trial Registration: ClinicalTrials.gov Identifier: NCT04518410.

The effect of perennial and annual wheat forages, fed with or without lucerne, on the fatty acid profile and oxidative status of lamb meat.

The current study investigated the fatty acid profile and oxidative status of the meat from lambs that were fed a novel perennial wheat or a conventional annual wheat, either as a cereal monoculture or lucerne biculture. Twelve lambs were assigned to each of the four dietary treatments (48 lambs in total) and held within individual pens for the duration of the 28 day feeding study. Lambs were slaughtered and the longissimus lumborum (LL) and semimembranosus (SM) muscles analysed. The independent effect of wheat type on fatty acid concentrations was negligible. The concentration of long-chain saturated and omega-6 polyunsaturated fatty acids was higher when lucerne was included in the diet. Only monounsaturated fatty acids were affected by the interaction between wheat type and lucerne. The three-way interaction between wheat type, lucerne and muscle was only significant for the concentration of C12:0 and anteiso-C15:0. The concentration of thiobarbituric reactive substances and vitamin E was higher in meat from lambs fed a lucerne biculture, compared with those fed a cereal monoculture. Furthermore, and independent to dietary treatment, higher concentration of omega-3, omega-6 and other health claimable fatty acids were found in the SM, compared with the LL. This information will support industry adoption of novel perennial wheat polycultures and help producers to utilise it as a dual-purpose crop for the production of grain and/or sheep meat.

The quality and mineral composition of the longissimus lumborum and semimembranosus muscles from lambs fed perennial or annual wheat forage with or without lucerne.

This study compared the effect of a novel perennial wheat forage and a conventional annual wheat forage, fed to lambs with or without lucerne, on the quality and mineral profile of the longissimus lumborum and semimembranosus muscles. This involved 48 Poll Dorset × Merino ewe lambs, 12 per treatment, managed for 28 days within individual pens. Consumer sensory panel scores showed 'good eating quality' for all samples irrespective of diet, a conclusion supported by the shear force, cooking loss, particle size, and intramuscular fat results. Drip loss was affected by a significant interaction between diet and muscle. The ultimate pH of meat from lambs fed annual wheat was highest. Comparable colour stability and purge results suggested that diet did not impact on lamb retail-potential. Sodium, sulphur and zinc concentrations were higher in the meat from lambs fed annual wheat, compared to perennial wheat. Overall, these outcomes support the use of perennial wheat as a forage for lamb production.

Post-mortem pH decline in lamb semitendinosus muscle and its relationship to the pH decline parameters of the longissimus lumborum muscle: A pilot study.

This study compared longissimus lumborum (LL) and semitendinosus (ST) muscles, in 48 lamb carcasses, to determine their pH decline parameters and achievement of ideal pH criteria (hitting the window). These include the pH at temperature 18 °C (pH@18) and temperature at pH 6 (temp@pH6). No practical difference were found between muscles for pH@18 or the temp@pH6, although there were differences between the experimental carcasses evaluated. Indeed, for all but three carcasses, there were insignificant differences between the LL and ST in terms of their pH@18. This outcome suggests that the lower value and more accessible ST muscle can be measured to determine lamb carcass pH decline parameters, instead of the LL. Because of the scale of this study, additional investigation is advised prior to any adoption.