Hyperspectral signals in the soil: Plant-soil hydraulic connection and disequilibrium as mechanisms of drought tolerance and rapid recovery.

Predicting soil water status remotely is appealing due to its low cost and large-scale application. During drought, plants can disconnect from the soil, causing disequilibrium between soil and plant water potentials at pre-dawn. The impact of this disequilibrium on plant drought response and recovery is not well understood, potentially complicating soil water status predictions from plant spectral reflectance. This study aimed to quantify drought-induced disequilibrium, evaluate plant responses and recovery, and determine the potential for predicting soil water status from plant spectral reflectance. Two species were tested: sweet corn (Zea mays), which disconnected from the soil during intense drought, and peanut (Arachis hypogaea), which did not. Sweet corn's hydraulic disconnection led to an extended 'hydrated' phase, but its recovery was slower than peanut's, which remained connected to the soil even at lower water potentials (-5 MPa). Leaf hyperspectral reflectance successfully predicted the soil water status of peanut consistently, but only until disequilibrium occurred in sweet corn. Our results reveal different hydraulic strategies for plants coping with extreme drought and provide the first example of using spectral reflectance to quantify rhizosphere water status, emphasizing the need for species-specific considerations in soil water status predictions from canopy reflectance.

Ruminating on soil carbon: Applying current understanding to inform grazing management.

Among options for atmospheric CO2 removal, sequestering soil organic carbon (SOC) via improved grazing management is a rare opportunity because it is scalable across millions of globally grazed acres, low cost, and has high technical potential. Decades of scientific research on grazing and SOC has failed to form a cohesive understanding of how grazing management affects SOC stocks and their distribution between particulate (POM) and mineral-associated organic matter (MAOM)-characterized by different formation and stabilization pathways-across different climatic contexts. As we increasingly look to grazing management for SOC sequestration on grazinglands to bolster our climate change mitigation efforts, we need a clear and collective understanding of grazing management's impact on pathways of SOC change to inform on-the-ground management decisions. We set out to review the effects of grazing management on SOC through a unified plant ecophysiology and soil biogeochemistry conceptual framework, where elements such as productivity, input quality, soil mineral capacity, and climate variables such as aridity co-govern SOC accumulation and distribution into POM and MAOM. To maximize applicability to grazingland managers, we discuss how common management levers that drive overall grazing pattern, including timing, intensity, duration, and frequency can be used to optimize mechanistic pathways of SOC sequestration. We discuss important research needs and measurement challenges, and highlight how our conceptual framework can inform more robust research with greater applicability for maximizing the use of grazing management to sequester SOC.

Thermal stressors during embryo incubation have limited ontogenic carryover effects in brook trout.

Winter climate is changing rapidly in northern latitudes, and these temperature events have effects on salmonid thermal biology. Stressors during winter egg incubation could reduce hatching success and physiological performance of fall-spawning fishes. Here we quantified the potential for ontogenic carryover effects from embryonic thermal stress in multiple wild and hatchery-origin populations of brook trout (Salvelinus fontinalis), a temperate ectotherm native to northeastern North America. Fertilized eggs from four populations were incubated over the winter in the laboratory in four differing thermal regimes: ambient stream-fed water, chronic warming (+2 °C), ambient with a mid-winter cold-shock, and short-term warming late during embryogenesis (to stimulate an early spring). We examined body size and upper thermal tolerance at the embryonic, fry (10 weeks post-hatch and 27-30 weeks post-hatch) and gravid adult (age 2+) life stages (overall N = 1482). In a separate experiment, we exposed developing embryos to acute seven-day heat stress events immediately following fertilization and at the eyed-egg stage, and then assessed upper thermal tolerance (CTmax) 37 weeks post-hatch. In all cases, fish were raised in common garden conditions after hatch (i.e., same temperatures). Our thermal treatments during incubation had effects that varied by life stage, with incubation temperature and life stage both affecting body size and thermal tolerance. Embryos incubated in warmer treatment groups had higher thermal tolerance; there was no effect of the mid-winter melt event on embryo CTmax. Ten weeks after hatch, fry from the ambient and cold-shock treatment groups had higher and less variable thermal tolerance than did the warmer treatment groups. At 27-30 post-hatch and beyond, differences in thermal tolerance among treatment groups were negligible. Collectively, our study suggests that brook trout only exhibit short-term carryover effects from thermal stressors during embryo incubation, with no lasting effects on phenotype beyond the first few months after hatch.

An in vivo screening platform identifies senolytic compounds that target p16INK4a+ fibroblasts in lung fibrosis.

The appearance of senescent cells in age-related diseases has spurred the search for compounds that can target senescent cells in tissues, termed senolytics. However, a major caveat with current senolytic screens is the use of cell lines as targets where senescence is induced in vitro, which does not necessarily reflect the identity and function of pathogenic senescent cells in vivo. Here, we developed a new pipeline leveraging a fluorescent murine reporter that allows for isolation and quantification of p16Ink4a+ cells in diseased tissues. By high-throughput screening in vitro, precision-cut lung slice (PCLS) screening ex vivo, and phenotypic screening in vivo, we identified a HSP90 inhibitor, XL888, as a potent senolytic in tissue fibrosis. XL888 treatment eliminated pathogenic p16Ink4a+ fibroblasts in a murine model of lung fibrosis and reduced fibrotic burden. Finally, XL888 preferentially targeted p16INK4a-hi human lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis (IPF), and reduced p16INK4a+ fibroblasts from IPF PCLS ex vivo. This study provides proof of concept for a platform where p16INK4a+ cells are directly isolated from diseased tissues to identify compounds with in vivo and ex vivo efficacy in mice and humans, respectively, and provides a senolytic screening platform for other age-related diseases.

Comparison of surgical or non-surgical management for non-acute anterior cruciate ligament injury: the ACL SNNAP RCT.

Background: Anterior cruciate ligament injury of the knee is common and leads to decreased activity and risk of secondary osteoarthritis of the knee. Management of patients with a non-acute anterior cruciate ligament injury can be non-surgical (rehabilitation) or surgical (reconstruction). However, insufficient evidence exists to guide treatment. Objective(s): To determine in patients with non-acute anterior cruciate ligament injury and symptoms of instability whether a strategy of surgical management (reconstruction) without prior rehabilitation was more clinically and cost-effective than non-surgical management (rehabilitation). Design: A pragmatic, multicentre, superiority, randomised controlled trial with two-arm parallel groups and 1:1 allocation. Due to the nature of the interventions, no blinding could be carried out. Setting: Twenty-nine NHS orthopaedic units in the United Kingdom. Participants: Participants with a symptomatic (instability) non-acute anterior cruciate ligament-injured knee. Interventions: Patients in the surgical management arm underwent surgical anterior cruciate ligament reconstruction as soon as possible and without any further rehabilitation. Patients in the rehabilitation arm attended physiotherapy sessions and only were listed for reconstructive surgery on continued instability following rehabilitation. Surgery following initial rehabilitation was an expected outcome for many patients and within protocol. Main outcome measures: The primary outcome was the Knee Injury and Osteoarthritis Outcome Score 4 at 18 months post randomisation. Secondary outcomes included return to sport/activity, intervention-related complications, patient satisfaction, expectations of activity, generic health quality of life, knee-specific quality of life and resource usage. Results: Three hundred and sixteen participants were recruited between February 2017 and April 2020 with 156 randomised to surgical management and 160 to rehabilitation. Forty-one per cent (n = 65) of those allocated to rehabilitation underwent subsequent reconstruction within 18 months with 38% (n = 61) completing rehabilitation and not undergoing surgery. Seventy-two per cent (n = 113) of those allocated to surgery underwent reconstruction within 18 months. Follow-up at the primary outcome time point was 78% (n = 248; surgical, n = 128; rehabilitation, n = 120). Both groups improved over time. Adjusted mean Knee Injury and Osteoarthritis Outcome Score 4 scores at 18 months had increased to 73.0 in the surgical arm and to 64.6 in the rehabilitation arm. The adjusted mean difference was 7.9 (95% confidence interval 2.5 to 13.2; p = 0.005) in favour of surgical management. The per-protocol analyses supported the intention-to-treat results, with all treatment effects favouring surgical management at a level reaching statistical significance. There was a significant difference in Tegner Activity Score at 18 months. Sixty-eight per cent (n = 65) of surgery patients did not reach their expected activity level compared to 73% (n = 63) in the rehabilitation arm. There were no differences between groups in surgical complications (n = 1 surgery, n = 2 rehab) or clinical events (n = 11 surgery, n = 12 rehab). Of surgery patients, 82.9% were satisfied compared to 68.1% of rehabilitation patients. Health economic analysis found that surgical management led to improved health-related quality of life compared to non-surgical management (0.052 quality-adjusted life-years, p = 0.177), but with higher NHS healthcare costs (£1107, p < 0.001). The incremental cost-effectiveness ratio for the surgical management programme versus rehabilitation was £19,346 per quality-adjusted life-year gained. Using £20,000-30,000 per quality-adjusted life-year thresholds, surgical management is cost-effective in the UK setting with a probability of being the most cost-effective option at 51% and 72%, respectively. Limitations: Not all surgical patients underwent reconstruction, but this did not affect trial interpretation. The adherence to physiotherapy was patchy, but the trial was designed as pragmatic. Conclusions: Surgical management (reconstruction) for non-acute anterior cruciate ligament-injured patients was superior to non-surgical management (rehabilitation). Although physiotherapy can still provide benefit, later-presenting non-acute anterior cruciate ligament-injured patients benefit more from surgical reconstruction without delaying for a prior period of rehabilitation. Future work: Confirmatory studies and those to explore the influence of fidelity and compliance will be useful. Trial registration: This trial is registered as Current Controlled Trials ISRCTN10110685; ClinicalTrials.gov Identifier: NCT02980367. Funding: This award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/140/63) and is published in full in Health Technology Assessment; Vol. 28, No. 27. See the NIHR Funding and Awards website for further award information.

The study aimed to find out whether it is better to offer surgical reconstruction or rehabilitation first to patients with a more long-standing injury of their anterior cruciate ligament in their knee. This injury causes physical giving way of the knee and/or sensations of it being wobbly (instability). The instability can affect daily activities, work, sport and can lead to arthritis. There are two main treatment options for this problem: non-surgical rehabilitation (prescribed exercises and advice from physiotherapists) or an operation by a surgeon to replace the damaged ligament (anterior cruciate ligament reconstruction). Although studies have highlighted the best option for a recently injured knee, the best management was not known for patients with a long-standing injury, perhaps occurring several months previously. Because the surgery is expensive to the NHS (around £100 million per year), it was also important to look at the costs involved. We carried out a study recruiting 316 non-acute anterior cruciate ligament-injured patients from 29 different hospitals and allocated each patient to either surgery or rehabilitation as their treatment option. We measured how well they did with special function and activity scores, patient satisfaction and costs of treatment. Patients in both groups improved substantially. It was expected that some patients in the rehabilitation group would want surgery if non-surgical management was unsuccessful. Forty-one per cent of patients who initially underwent rehabilitation subsequently elected to have reconstructive surgery. Overall, the patients allocated to the surgical reconstruction group had better results in terms of knee function and stability, activity level and satisfaction with treatment than patients allocated to the non-operative rehabilitation group. There were few problems or complications with either treatment option. Although the surgery was a more expensive treatment option, it was found to be cost-effective in the UK setting. The evidence can be discussed in shared decision-making with anterior cruciate ligament-injured patients. Both strategies of management led to improvement. Although a rehabilitation strategy can be beneficial, especially for recently injured patients, it is advised that later-presenting non-acute and more long-standing anterior cruciate ligament-injured patients undergo surgical reconstruction without necessarily delaying for a period of rehabilitation.