Acute graft-versus-host disease (aGVHD) still remains a major limiting factor following allogeneic stem cell transplantation (AlloSCT) in pediatric recipients. Mycophenolate mofetil (MMF), an uncompetitive selective inhibitor of inosine monophosphate dehydrogenase, is a new immunosuppressant agent without major mucosal, hepatic, or renal toxicity compared to other prophylactic aGVHD immunosuppressant drugs. Although there has been an extensive pharmacokinetic (PK) experience with MMF administration following solid organ transplantation in children, there is a paucity of PK data following its use in pediatric AlloSCT recipients. We investigated the safety and PK of MMF as GVHD prophylaxis following intravenous (i.v.) and oral (p.o.) administration (900 mg/m(2) every 6 hours) in conjunction with tacrolimus, after myeloablative (MA) and nonmyeloablative (NMA) conditioning and AlloSCT in 3 distinct age groups of pediatric AlloSCT recipients (0-6 years, 6-12 years, and 12-16 years). Mycophenolic acid (MPA) in plasma samples was measured either by high-performance liquid chromatography (HPLC) or liquid chromatography/mass spectrometry (LC/MS/MS) as we have previously described. Plasma samples were obtained at baseline and at 0.5, 1, 2, 3, 4, and 6 hours after i.v. dosing on days +1, +7, +14, and at 2 time points between day +45 and +100 after p.o. administration post AlloSCT. MPA PK analysis included AUC (0-6 hours), C(max), T(max), C(ss), V(ss), C trough (C(0)), CL, and T((1/2).) Thirty-eight patients, with a median age of 8 years (0.33-16 years), 20/18 M:F ratio, 21/17 malignant/nonmalignant disease, 17/21 MA: NMA conditioning, 16 of 22 related/unrelated allografts. Median time to myeloid and platelet engraftment was 18 and 31 days, respectively. Mean donor chimerism on day +60 and +100 was 83% and 90%, respectively. Probability of developing aGVHD grade II-IV and extensive chronic GVHD (cGVHD) was 54% and 34%, respectively. There was significant intra- and interpatient MMF PK variability. There was a significant increase in i.v. MPA area under the curve (AUC)(0-6 hour) and C(max) (P < .0003) and a significant decrease in CL(ss) (P < .002) and V(ss) (P < .001) on day +14 versus day +7. Children <12 years of age had a significant increase in i.v. MPA T(max) (P = .01), V(ss) (P = .028), and CL(ss) (P < .001) compared to the older age group. There was a trend in increased i.v. MPA CL(ss) following MA versus NMA conditioning (P < .054); i.v. and p.o. MMF administration (900 mg/m(2) every 6 hours) in combination with tacrolimus was well tolerated in pediatric AlloSCT recipients. There was a significant increase in MPA exposure on day +14 versus day +7, suggesting improved enterohepatic recirculation at day +14 post-AlloSCT. Children <12 years of age appear to have a significantly different MPA PK profile compared to older children and adolescents and may require more frequent dosing.

Summary Immune reconstitution appears to be delayed following myeloablative conditioning (MAC) and umbilical cord blood transplantation (UCBT) in paediatric recipients. Although reduced toxicity conditioning (RTC) vs. MAC prior to allogeneic stem cell transplantation is associated with decreased transplant-related mortality, the effects of RTC vs. MAC prior to UCBT on immune reconstitution and risk of graft-versus-host disease (GVHD) are unknown. In 88 consecutive paediatric recipients of UCBT, we assessed immune cell recovery and immunoglobulin reconstitution at days +100, 180 and 365 and analysed risk factors associated with acute and chronic GVHD. Immune cell subset recovery, immunoglobulin reconstitution, and the incidence of opportunistic infections did not differ significantly between MAC vs. RTC groups. In a Cox model, MAC vs. RTC recipients had significantly higher risk of grade II-IV acute GVHD (Hazard Ratio [HR] 6.1, p=0.002) as did recipients of 4/6 vs. 5-6/6 HLA-matched UCBT (HR 3.1, p=0.03), who also had significantly increased risk of chronic GVHD (HR 18.5, p=0.04). In multivariate analyses, MAC vs. RTC was furthermore associated with significantly increased transplant-related (Odds Ratio 26.8, p=0.008) and overall mortality (HR=4.1, p=0.0001). The use of adoptive cellular immunotherapy to accelerate immune reconstitution and prevent and treat opportunistic infections and malignant relapse following UCBT warrants further investigation.

Monoculture cropping systems currently dominate temperate agroecosystems. However, intercropping can provide valuable benefits, including greater yield stability, increased total productivity, and resilience in the face of pest and disease outbreaks. Plant breeding efforts in temperate field crops are largely focused on monoculture production, but as intercropping becomes more widespread, there is a need for cultivars adapted to these cropping systems. Cultivar development for intercropping systems requires a systems approach, from the decision to breed for intercropping systems through the final stages of variety testing and release. Design of a breeding scheme should include information about species variation for performance in intercropping, presence of genotype × management interaction, observation of key traits conferring success in intercropping systems, and the specificity of intercropping performance. Together this information can help to identify an optimal selection scheme. Agronomic and ecological knowledge are critical in the design of selection schemes in cropping systems with greater complexity, and interaction with other researchers and key stakeholders inform breeding decisions throughout the process. This review explores the above considerations through three case studies: (1) forage mixtures, (2) perennial groundcover systems (PGC), and (3) soybean-pennycress intercropping. We provide an overview of each cropping system, identify relevant considerations for plant breeding efforts, describe previous breeding focused on the cropping system, examine the extent to which proposed theoretical approaches have been implemented in breeding programs, and identify areas for future development.

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Drill-interseeding, broadcast-interseeding, and post-harvest drilling for establishment of overwintering cover crops after no-till corn (Zea mays L.) each present distinct challenges and benefits. Experiments were conducted at the Beltsville Agricultural Research Center (Beltsville, MD) across three growing seasons (2013-2014, 2014-2015, 2015-2016) to evaluate the relative performance of these three establishment methods across four cover crop treatments: (a) cereal rye (Secale cereale L.), (b) annual ryegrass [Lolium perenne L. ssp. multiflorum (Lam.) Husnot], (c) a legume mixture including red clover (Trifolium pratense L.), crimson clover (Trifolium incarnatum L.), and hairy vetch (Vicia villosa Roth), and (d) a grass-legume mixture including annual ryegrass, red clover, crimson clover, and hairy vetch. Both fall and spring biomass showed a significant three-way interaction effect among cover crop, establishment method, and year. Cereal rye had the greatest biomass with late post-harvest drilling but produced less fall and spring biomass than other cover crops in the drillinterseeded treatments in two of the three growing seasons. The drill-interseeded legume mixture produced less spring biomass than annual ryegrass and the grass-legume mixture when established at a later corn growth stage. Our results highlight potential pitfalls of each establishment method and cover crop, depending on annual variability in weather and management. 1 INTRODUCTION Winter cover crops provide a number of important ecosystem services including reduced erosion and nutrient losses, improved soil physical properties, and weed suppression (Blanco-Canqui et al., 2015; Steele, Coale, & Hill, 2012). Cover crop usage in the United States increased 49% from 2012 to 2017; 6.2 million ha were planted to cover crops in 2017 (USDA-NASS, 2019). Cover crop adoption varies widely across U.S. regions due to site-specific constraints (Wade, Claassen, & Wallander, 2015). However, according to a recent national survey of farmers, concern for poor