The Influence of Acute Hypoxia on Oxygen Uptake and Muscle Oxygenation Kinetics During Cycling Exercise in Prepubertal Boys.

PURPOSE: To examine the effect of normobaric hypoxia on pulmonary oxygen uptake (V˙O2) and muscle oxygenation kinetics during incremental and moderate-intensity exercise in children. METHODS: Eight prepubertal boys (9-11 y) performed incremental cycle tests to exhaustion in both normoxia and hypoxia (fraction of inspired O2 of 15%) followed by repeat 6-minute transitions of moderate-intensity exercise in each condition over subsequent visits. RESULTS: Maximal oxygen uptake (V˙O2max) was reduced in hypoxia compared with normoxia (1.69 [0.20] vs 1.87 [0.26] L·min-1, P = .028), although the gas exchange threshold was not altered in absolute terms (P = .33) or relative to V˙O2max (P = .78). During moderate-intensity exercise, the phase II V˙O2 time constant (τ) was increased in hypoxia (18 [9] vs 24 [8] s, P = .025), with deoxyhemoglobin τ unchanged (17 [8] vs 16 [6], P ≥ .28). CONCLUSIONS: In prepubertal boys, hypoxia reduced V˙O2max and slowed V˙O2 phase II kinetics during moderate-intensity exercise, despite unchanged deoxyhemoglobin kinetics. These data suggest an oxygen delivery dependence of V˙O2max and moderate-intensity V˙O2 kinetics under conditions of reduced oxygen availability in prepubertal boys.

Global-to-Local Dependencies in Phosphorus Mass Flows and Markets: Pathways to Improving System Resiliency in Response to Exogenous Shocks.

Uneven global distribution of phosphate rock deposits and the supply chains to transport phosphorus (P) make P fertilizers vulnerable to exogenous shocks, including commodity market shocks; extreme weather events or natural disasters; and geopolitical instability, such as trade disputes, disruption of shipping routes, and war. Understanding bidirectional risk transmission (global-to-local and local-to-global) in P supply and consumption chains is thus essential. Ignoring P system interdependencies and associated risks could have major impacts on critical infrastructure operations and increase the vulnerability of global food systems. We highlight recent unanticipated events and cascading effects that have impacted P markets globally. We discuss the need to account for exogenous shocks in local assessments of P flows, policies, and infrastructure design choices. We also provide examples of how accounting for undervalued global risks to the P industry can hasten the transition to a sustainable P future. For example, leveraging internal P recycling loops, improving plant P use efficiency, and utilizing legacy soil P all enhance system resiliency in the face of exogenous shocks and long-term anticipated threats. Strategies applied at the local level, which are embedded within national and global policy systems, can have global-scale impacts in derisking the P supply chain.

Seasonal drives on potentially toxic elements dynamics in a tropical estuary impacted by mine tailings.

This study investigates the impact of seasonality on estuarine soil geochemistry, focusing on redox-sensitive elements, particularly Fe, in a tropical estuary affected by Fe-rich mine tailings. We analyzed soil samples for variations in particle size, pH, redox potential (Eh), and the content of Fe, Mn, Cr, Cu, Ni, and Pb. Additionally, sequential extraction was employed to understand the fate of these elements. Results revealed dynamic changes in the soil geochemical environment, transitioning between near-neutral and suboxic/anoxic conditions in the wet season and slightly acidic to suboxic/oxic conditions in the dry season. During the wet season, fine particle deposition (83%) rich in Fe (50 g kg-1), primarily comprising crystalline Fe oxides, occurred significantly. Conversely, short-range ordered Fe oxides dominated during the dry season. Over consecutive wet/dry seasons, substantial losses of Fe (-55%), Mn (-41%), and other potentially toxic elements (Cr: -44%, Cu: -31%, Ni: -25%, Pb: -9%) were observed. Despite lower pseudo-total PTE contents, exchangeable PTEs associated with carbonate content increased over time (Cu: +188%, Ni: +557%, Pb: +99%). Modeling indicated climatic variables and short-range oxides substantially influenced PTE bioavailability, emphasizing the ephemeral Fe oxide control during the wet season and heightened ecological and health risks during the dry seasons.

Contrasting plant-induced changes in heavy metals dynamics: Implications for phytoremediation strategies in estuarine wetlands.

Wetland plants play a crucial role in regulating soil geochemistry, influencing heavy metal (HM) speciation, bioavailability, and uptake, thus impacting phytoremediation potential. We hypothesized that variations in HM biogeochemistry within estuarine soils are controlled by distinct estuarine plant species. We evaluated the soils (pH, redox potential, rhizosphere pH, HM total concentration, and geochemical fractionation), plant parts (shoot and root), and iron plaques of three plants growing in an estuary affected by Fe-rich mine tailings. Though the integration of multiple plant and soil analysis, this work emphasizes the importance of considering geochemical pools of HM for predicting their fate. Apart from the predominance of HM associated with Fe oxides, Typha domingensis accumulated the highest Cr and Ni contents in their shoots (> 100 mg kg-1). In contrast, Hibiscus tiliaceus accumulated more Cu and Pb in their roots (> 50 mg kg-1). The differences in rhizosphere soil conditions and root bioturbation explained the different potentials between the plants by altering the soil dynamics and HM's bioavailability, ultimately affecting their uptake. This study suggests that Eleocharis acutangula is not suitable for phytoextraction or phytostabilization, whereas Typha domingensis shows potential for Cr and Ni phytoextraction. In addition, we first showed Hibiscus tiliaceus as a promising wood species for Cu and Pb phytostabilization.

Commercial compost amendments inhibit the bioavailability and plant uptake of per- and polyfluoroalkyl substances in soil-porewater-lettuce systems.

Compost is widely used in agriculture as fertilizer while providing a practical option for solid municipal waste disposal. However, compost may also contain per- and polyfluoroalkyl substances (PFAS), potentially impacting soils and leading to PFAS entry into food chains and ultimately human exposure risks via dietary intake. This study examined how compost affects the bioavailability and uptake of eight PFAS (two ethers, three fluorotelomer sulfonates, and three perfluorosulfonates) by lettuce (Lactuca sativa) grown in commercial organic compost-amended, PFAS spiked soils. After 50 days of greenhouse experiment, PFAS uptake by lettuce decreased (by up to 90.5 %) with the increasing compost amendment ratios (0-20 %, w/w), consistent with their decreased porewater concentrations (by 30.7-86.3 %) in compost-amended soils. Decreased bioavailability of PFAS was evidenced by the increased in-situ soil-porewater distribution coefficients (Kd) (by factors of 1.5-7.0) with increasing compost additions. Significant negative (or positive) correlations (R2 ≥ 0.55) were observed between plant bioaccumulation (or Kd) and soil organic carbon content, suggesting that compost amendment inhibited plant uptake of PFAS mainly by increasing soil organic carbon and enhancing PFAS sorption. However, short-chain PFAS alternatives (e.g., perfluoro-2-methoxyacetic acid (PFMOAA)) were effectively translocated to shoots with translocation factors > 2.9, increasing their risks of contamination in leafy vegetables. Our findings underscore the necessity for comprehensive risk assessment of compost-borne PFAS when using commercial compost products in agricultural lands.

Adapting, restarting, and terminating a randomised control trial for people with cystic fibrosis: Reflections on the impact of the COVID-19 pandemic upon research in a clinical population.

Background: Habitual physical activity (PA) and exercise form a cornerstone of the management of cystic fibrosis (CF), a genetically inherited pulmonary and digestive condition - whereby telehealth platforms have been proposed as a mechanism to engage remotely people with CF in PA and exercise. Methods: To test this, in early 2020, the 'ActivOnline: Physical Activity in Cystic Fibrosis Trial' (ActiOn PACT) randomised control trial was established to examine whether an online intervention was effective at increasing PA in adolescents and adults with CF. Results: The emergence of the COVID-19 pandemic in 2020 forced this trial to be paused and modified, with the adoption of online recruitment and remote assessment of outcome measures. Despite such adaptations in accord with frameworks developed by the National Institute for Health Research, this trial failed to recruit and was subsequently terminated. Conclusions: This article details the authors reflections upon the proposed reasons for lack of recruitment, including improved technology and medications for people with CF, and contextualises this finding in relation to the wider issue of non-reporting of trial results in clinical research.

Getting Your First Publication in Medical Education-Why? What? Where? How?

The process of getting one's work published is a major milestone for many in their early academic and clinical careers. However, this process can be confusing and overwhelming for many who have yet to publish themselves. There are differing motivators for publishing work in our early career stages, alongside considerations, such as what we publish, where we decide to submit work, and how we logistically undertake the submission process. This commentary provides a holistic overview for the early career medical educator, empowering them to take the bold steps toward "getting published."

Molecular and Pathologic Characterization of YAP1-Expressing Small Cell Lung Cancer Cell Lines Leads to Reclassification as SMARCA4-Deficient Malignancies.

PURPOSE: The classification of small cell lung cancer (SCLC) into distinct molecular subtypes defined by ASCL1, NEUROD1, POU2F3, or YAP1 (SCLC-A, -N, -P, or -Y) expression, paves the way for a personalized treatment approach. However, the existence of a distinct YAP1-expressing SCLC subtype remains controversial. EXPERIMENTAL DESIGN: To better understand YAP1-expressing SCLC, the mutational landscape of human SCLC cell lines was interrogated to identify pathogenic alterations unique to SCLC-Y. Xenograft tumors, generated from cell lines representing the four SCLC molecular subtypes, were evaluated by a panel of pathologists who routinely diagnose thoracic malignancies. Diagnoses were complemented by transcriptomic analysis of primary tumors and human cell line datasets. Protein expression profiles were validated in patient tumor tissue. RESULTS: Unexpectedly, pathogenic mutations in SMARCA4 were identified in six of eight SCLC-Y cell lines and correlated with reduced SMARCA4 mRNA and protein expression. Pathologist evaluations revealed that SMARCA4-deficient SCLC-Y tumors exhibited features consistent with thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UT). Similarly, the transcriptional profile SMARCA4-mutant SCLC-Y lines more closely resembled primary SMARCA4-UT, or SMARCA4-deficient non-small cell carcinoma, than SCLC. Furthermore, SMARCA4-UT patient samples were associated with a YAP1 transcriptional signature and exhibited strong YAP1 protein expression. Together, we found little evidence to support a diagnosis of SCLC for any of the YAP1-expressing cell lines originally used to define the SCLC-Y subtype. CONCLUSIONS: SMARCA4-mutant SCLC-Y cell lines exhibit characteristics consistent with SMARCA4-deficient malignancies rather than SCLC. Our findings suggest that, unlike ASCL1, NEUROD1, and POU2F3, YAP1 is not a subtype defining transcription factor in SCLC. See related commentary by Rekhtman, p. 1708.

Predatory publishing in medical education: a rapid scoping review.

BACKGROUND: Academic publishing is a cornerstone of scholarly communications, yet is unfortunately open to abuse, having given rise to 'predatory publishers'- groups that employ aggressive marketing tactics, are deficient in methods and ethics, and bypass peer review. Preventing these predatory publishers from infiltrating scholarly activity is of high importance, and students must be trained in this area to increase awareness and reduce use. The scope of this issue in the context of medical students remains unknown, and therefore this sought to examine the breadth of the current literature base. METHODS: A rapid scoping review was undertaken, adhering to adapted PRISMA guidelines. Six databases (ASSIA, EBSCO, Ovid, PubMed, Scopus, Web of Science) were systematically searched for content related to predatory publishing and medical students. Results were single-screened, facilitated by online reviewing software. Resultant data were narratively described, with common themes identified. RESULTS: After searching and screening, five studies were included, representing a total of 1338 students. Two predominant themes- understanding, and utilisation- of predatory publishers was identified. These themes revealed that medical students were broadly unaware of the issue of predatory publishing, and that a small number have already, or would consider, using their services. CONCLUSION: There remains a lack of understanding of the threat that predatory publishers pose amongst medical students. Future research and education in this domain will be required to focus on informing medical students on the issue, and the implication of engaging with predatory publishers.

Inactivation of siderophore iron-chelating moieties by the fungal wheat root symbiont Pyrenophora biseptata.

We investigated the ability of four plant and soil-associated fungi to modify or degrade siderophore structures leading to reduced siderophore iron-affinity in iron-limited and iron-replete cultures. Pyrenophora biseptata, a melanized fungus from wheat roots, was effective in inactivating siderophore iron-chelating moieties. In the supernatant solution, the tris-hydroxamate siderophore desferrioxamine B (DFOB) underwent a stepwise reduction of the three hydroxamate groups in DFOB to amides leading to a progressive loss in iron affinity. A mechanism is suggested based on the formation of transient ferrous iron followed by reduction of the siderophore hydroxamate groups during fungal high-affinity reductive iron uptake. P. biseptata also produced its own tris-hydroxamate siderophores (neocoprogen I and II, coprogen and dimerum acid) in iron-limited media and we observed loss of hydroxamate chelating groups during incubation in a manner analogous to DFOB. A redox-based reaction was also involved with the tris-catecholate siderophore protochelin in which oxidation of the catechol groups to quinones was observed. The new siderophore inactivating activity of the wheat symbiont P. biseptata is potentially widespread among fungi with implications for the availability of iron to plants and the surrounding microbiome in siderophore-rich environments.

Cardiopulmonary Exercise Testing Provides Prognostic Information in Advanced Cystic Fibrosis Lung Disease.

Rationale: Cardiopulmonary exercise testing (CPET) provides prognostic information in cystic fibrosis (CF); however, its prognostic value for patients with advanced CF lung disease is unknown. Objectives: To determine the prognostic value of CPET on the risk of death or lung transplant (LTX) within 2 years. Methods: We retrospectively collected data from 20 CF centers in Asia, Australia, Europe, and North America on patients with a forced expiratory volume in 1 second (FEV1) ⩽ 40% predicted who performed a cycle ergometer CPET between January 2008 and December 2017. Time to death/LTX was analyzed using mixed Cox proportional hazards regression. Conditional inference trees were modeled to identify subgroups with increased risk of death/LTX. Results: In total, 174 patients (FEV1, 30.9% ± 5.8% predicted) were included. Forty-four patients (25.5%) died or underwent LTX. Cox regression analysis adjusted for age, sex, and FEV1 revealed percentage predicted peak oxygen uptake ([Formula: see text]o2peak) and peak work rate (Wpeak) as significant predictors of death/LTX: adjusted hazard ratios per each additional 10% predicted were 0.60 (95% confidence interval, 0.43-0.90; P = 0.008) and 0.60 (0.48-0.82; P < 0.001). Tree-structured regression models, including a set of 11 prognostic factors for survival, identified Wpeak to be most strongly associated with 2-year risk of death/LTX. Probability of death/LTX was 45.2% for those with a Wpeak ⩽ 49.2% predicted versus 10.9% for those with a Wpeak > 49.2% predicted (P < 0.001). Conclusions: CPET provides prognostic information in advanced CF lung disease, and Wpeak appears to be a promising marker for LTX referral and candidate selection.

Growth Rate Distribution and Potential Non-Linear Relationship between Body Weight and Walking Ability in Turkeys.

The aim of this study was to investigate the potential non-linear relationship between growth and walking ability (WA). The phenotypic data included body weights at 12 and 20 weeks and WA at 20 weeks of age measured on 276,059 male turkeys. The growth rate at three age periods (0 to 12, 12 to 20 and 0 to 20 weeks) was calculated. Each bird was assigned to one of the quartiles of the growth rate distribution for each age period. Between the first and fourth quartiles, the incidence of score 1 (bad WA) increased by 31, 18, and 33% for the first, second, and third age periods, respectively. For good WA (scores 4, 5, and 6), the incidence decreased by 55, 66, and 72% between the first and fourth quartiles for the first, second, and third age periods, respectively. Estimates of heritability of WA ranged between 0.18 and 0.26. The genetic correlations between adjacent growth rate quartiles were high and decayed as the interval between quartiles increased. The magnitude of the variation in the incidence of walking scores and genetic correlations across the growth rate quartiles point towards a non-linear relationship between growth and mobility suggesting other factors may affect walking ability.

Pyrolysis temperature and biochar redox activity on arsenic availability and speciation in a sediment.

Biochar is widely used for water and soil remediation in part because of its local availability and low production cost. However, its effectiveness depends on physicochemical properties related to its feedstock and pyrolysis temperature, as well as the environmental conditions of its use site. Furthermore, biochar is susceptible to natural aging caused by changes in soil or sediment moisture, which can alter its redox properties and interactions with contaminants such as arsenic (As). In this study, we investigated the effect of pyrolysis temperature and biochar application on the release and transformations of As in contaminated sediments subjected to redox fluctuations. Biochar application and pyrolysis temperature played an important role in As species availability, As methylation, and dissolved organic carbon concentration. Furthermore, successive flooding cycles that induced reductive conditions in sediments increased the As content in the solution by up to seven times. In the solid phase, the application of biochar and the flooding cycle altered the spatial distribution and speciation of carbon, iron (Fe) and As. In general, the application of biochar decreased the reduction of Fe(III) and As(V) after the first cycle of flooding. Our results demonstrate that the flooding cycle plays an important role in the reoxidation of biochar to the point of enhancing the immobilization of As.

Research Note: Analysis of body weight and walking ability in turkeys and the prediction of categorical responses across systematic effect classes using a linear threshold model.

Heavy selection for growth in turkeys has led to a decay in leg soundness and walking ability. In this study, different models and traits were used to investigate the genetic relationships between body weight (BW) and walking ability (WA) in a turkey population. The data consisted of BW and WA traits collected on 276,059 male birds. Body weight was measured at 12 and 20 wk and WA at 20 wk of age. For WA, birds were scored based on a 1 (bad) to 6 (good) grading system. Due to the small number of records with scores 5 and 6, birds with WA scores of 4, 5, and 6 were grouped together resulting in only 4 classes. Additionally, a binary classification of WA (scores 1 and 2 = Similarly, an estimate of the genetic correlation between WA and BW at 20 wk was -0.45, indicating a more pronounced class 1; scores 3, 4, 5, and 6 = class 2) was evaluated. The inheritability estimates of WA ranged between 0.25 and 0.27 depending on the number of classes. The Heritability of BW at 12 and 20 wk was 0.44 and 0.51, respectively. The genetic correlation between WA and BW at 12 wk was around -0.35, indicating that heavy birds tend to have poor WA. antagonistic relationship between BW and WA. The genetic correlation between BW at 12 and 20 wk was positive and high (0.80). The residual correlation between WA and BW at 12 and 20 wk of age was -0.07 and -0.02, respectively. The residual correlation between body weight traits was 0.57. Similar results were observed when a binary classification was adopted for WA. The probability of an individual with a given genetic merit expressing a certain class of WA was determined for different fixed effect designations. Predictive probabilities clearly showed that birds when hatched in the winter would have a small chance to exhibit good WA phenotypes.

Agreement between left and right middle cerebral artery blood velocity responses to incremental and constant work-rate exercise in healthy males and females.

Objective.To quantify the agreement between left and right middle cerebral artery blood velocity (MCAv) responses to incremental and constant work-rate exercise in adults.ApproachSeventeen healthy adults (23.8 ± 2.4 years, 9 females) completed a ramp incremental test to exhaustion on a cycle ergometer, three 6-minute transitions at a moderate-intensity, and three at a heavy-intensity, all on separate days. Bilateral MCAv was measured throughout using transcranial Doppler ultrasonography, with left and right MCAv data analysed separately. Data were analysed at baseline, gas exchange threshold, respiratory compensation point and exhaustion during ramp incremental exercise. MCAv responses to constant work-rate exercise were analysed using a mono-exponential model, to determine time- and amplitude-based kinetic response parameters.Main ResultsLeft and right MCAv responses to incremental and constant work-rate exercise were significantly, strongly and positively correlated (r≥ 0.61,P< 0.01). Coefficient of variation (left versus right) ranged from 7.3%-20.7%, 6.4%-26.2% and 5.9%-22.5% for ramp, moderate and heavy-intensity exercise, respectively. The relative change in MCAv from baseline was higher in the right compared to left MCAv during ramp, moderate and heavy-intensity exercise (allP< 0.05), but the effect sizes were small (d≤ 0.4). Small mean left-right differences were present during ramp incremental exercise at all time-points (<6 cm s-1; <4%), and for all kinetic parameters during moderate and heavy-intensity exercise (<3 cm s-1, <3%, <4 s).SignificanceThese findings demonstrate similarities between left and right MCAv responses to incremental and constant-work rate exercise in adults on a group-level, but also highlight individual variation in the agreement between left and right MCAv exercise responses.

Pharmacogenetic activation of parvalbumin interneurons in the prefrontal cortex rescues cognitive deficits induced by adolescent MK801 administration.

The cognitive symptoms of schizophrenia (SZ) present a significant clinical burden. They are treatment resistant and are the primary predictor of functional outcomes. Although the neural mechanisms underlying these deficits remain unclear, pathological GABAergic signaling likely plays an essential role. Perturbations with parvalbumin (PV)-expressing fast-spiking (FS) interneurons in the prefrontal cortex (PFC) are consistently found in post-mortem studies of patients with SZ, as well as in animal models. Our studies have shown decreased prefrontal synaptic inhibition and PV immunostaining, along with working memory and cognitive flexibility deficits in the MK801 model. To test the hypothesized association between PV cell perturbations and impaired cognition in SZ, we activated prefrontal PV cells by using an excitatory DREADD viral vector with a PV promoter to rescue the cognitive deficits induced by adolescent MK801 administration in female rats. We found that targeted pharmacogenetic upregulation of prefrontal PV interneuron activity can restore E/I balance and improve cognition in the MK801 model. Our findings support the hypothesis that the reduced PV cell activity levels disrupt GABA transmission, resulting in the disinhibition of excitatory pyramidal cells. This disinhibition leads to an elevated prefrontal excitation/inhibition (E/I) balance that could be causal for cognitive impairments. Our study provides novel insights into the causal role of PV cells in cognitive function and has clinical implications for understanding the pathophysiology and management of SZ.

Multiphasic mixed growth models for turkeys.

Growth models are important for optimization of feed formulation and breeding programs in turkeys. The objectives of this study were 1) to compare sex and line differences in turkeys in parameter estimates of mono- and di-phasic Gompertz growth models, and 2) to evaluate mono and diphasic mixed Gompertz growth models to determine the variation in parameter estimates in a group of female line turkey toms. A total of 1,056 manually recorded weekly average body weight (BW) observations from male and female turkeys of a male and female line from weeks 1 to 20 were used for objective 1. Daily median values of automatically collected individual BW of female line turkey toms were used for objective 2 and random components associated with individual subject animals related to mature weight and/or timing of maximum gain during each phase were introduced in the Gompertz model. Growth curve shapes were different between male line toms, male line hens, female line toms, and female line hens (P < 0.001). However, inflection points were similar between male and female line toms and between male and female line hens (14.06 vs. 13.72 wk and 11.22 and 10.71 wk, respectively), while mature BW differed between lines by 6.49 and 3.81 kg for toms and hens, respectively. The normalized growth rate constant (growth rate constant corrected for mature weight) was around the same magnitude between male and female line toms (0.0031 vs. 0.0038, respectively), but slightly lower in male line hens compared to female line hens (0.0072 vs. 0.0091, respectively). Diphasic Gompertz models described growth better in all line × sex combinations compared to the monophasic models (P < 0.001) and mixed diphasic Gompertz models showed improved fit over mixed monophasic Gompertz models. The correlation structure of the random components identified that individuals with a higher mature weight had a later inflection point and lower growth rate coefficients. These results provide tools for improved breeding practices and a structure to evaluate the effects of dietary or environmental factors on growth trajectories.

Turkeys have been bred for several purposes over the past decades. We studied growth patterns of turkeys of two genetic lines bred for either meat production or egg production. Mathematical equations were designed and fitted to describe the average bodyweight of several consecutively grown groups of turkeys. Similarly, individual body weight was measured and studied in one group of male turkeys, to detect differences in growth patterns between individual turkeys. It showed that there were differences between both sexes as well as between both lines in the shape of the growth curve. The age at which males and females grew fastest was similar between meat production and egg production type turkeys, for males around 13 to 14 wk and for females around 10 to 11 wk. Males of the meat production line grew 6.5 kg heavier than males of the egg production line, whereas females of the meat production line grew 3.8 kg heavier than females of the egg production line. Individual turkeys that have a heavier mature weight grow at a slower pace and delay the growth spurt associated with sexual maturation. With these outcomes, turkey feed producers and genetic companies can better study and steer the desired growth of turkeys.

Expert guidelines on exercise and physical activity for people with cystic fibrosis.

Research has shown that there is a lack of confidence and understanding in how to use exercise for managing cystic fibrosis. This editorial discusses the key points of a consensus statement that highlights what is and is not known about the relationship between cystic fibrosis and exercise.

Assessment of multiple herbicide protection seed treatments for seed-based restoration of native perennial bunchgrasses and sagebrush across multiple sites and years.

The invasion of exotic, annual plant species is a leading contributor to ecological degradation in drylands globally, and the use of pre-emergent herbicide to control these species is common. Pre-emergent herbicides pose challenges for seed-based restoration due to toxicity to the seeds of desired species. Herbicide protection (HP) technologies pose a potential solution by using activated carbon seed treatments to protect desirable seeds from herbicide exposure. In the sagebrush steppe ecosystem of North America, we used an adaptive small plot design over three planting years to test for effects on seeding outcomes (seedling density and size) of large and small multi-seed HP pellets, several single-seed HP coatings, and carbon banding treatments at geographically dispersed sites for several perennial bunchgrasses and the keystone perennial shrub, Wyoming big sagebrush. We also compared different methods of seed delivery and litter pre-seeding management. Seeding success was low overall, especially for sagebrush, and it was clear that other, often less predictable barriers to establishment than herbicide exposure, such as inadequate spring moisture, were strong drivers of seeding outcomes. Despite this, HP treatments were associated with higher seedling density than bare seed in multiple instances, most notably for grasses. The large HP pellet occasionally outperformed the small HP pellet, and several HP coatings performed similarly to the small pellet. Surprisingly, we did not see consistent negative effects of pre-emergent herbicide on unprotected bare seed. We conclude that HP seed treatments show some promise to improve seeding success in the presence of herbicide, but that consistent success will require further improvements to HP treatments as well as integration with other innovations and approaches.