Synergism between production and soil health through crop diversification, organic amendments and crop protection in wheat-based systems

One of the critical challenges in agriculture is enhancing yield without compromising its foundation, a healthy environment and, particularly, soils. Hence, there is an urgent need to identify management practices that simultaneously support soil health and production and help achieve environmentally sound production systems.To investigate how management influences production and soil health under realistic agronomic conditions, we conducted an on-farm study involving 60 wheat fields managed conventionally, under no-till or organically. We assessed 68 variables defining management, production and soil health properties. We examined how management systems and individual practices describing crop diversification, fertiliser inputs, agrochemical use and soil disturbance influenced production-quantity and quality-and soil health focusing on aspects ranging from soil organic matter over soil structure to microbial abundance and diversity.Our on-farm comparison showed marked differences between soil health and production in the current system: organic management resulted in the best overall soil health (+47%) but the most significant yield gap (-34%) compared to conventional management. No-till systems were generally intermediate, exhibiting a smaller yield gap (-17%) and only a marginally improved level of soil health (+5%) compared to conventional management. Yet, the overlap between management systems in production and soil health properties was considerably large.Our results further highlight the importance of soil health for productivity by revealing positive associations between crop yield and soil health properties, particularly under conventional management, whereas factors such as weed pressure were more dominant in organic systems.None of the three systems showed advantages in supporting production-soil health-based multifunctionality. In contrast, a cross-system analysis suggests that multifunctional agroecosystems could be achieved through a combination of crop diversification and organic amendments with effective crop protection.Synthesis and applications: Our on-farm study implies that current trade-offs in managing production and soil health could be overcome through more balanced systems incorporating conventional and alternative approaches. Such multifunctionality supporting systems could unlock synergies between vital ecosystem services and help achieve productive yet environmentally sound agriculture supported by healthy soils

Synergism between production and soil health through crop diversification, organic amendments and crop protection in wheat‐based systems

One of the critical challenges in agriculture is enhancing yield without compromising its foundation, a healthy environment and, particularly, soils. Hence, there is an urgent need to identify management practices that simultaneously support soil health and production and help achieve environmentally sound production systems. To investigate how management influences production and soil health under realistic agronomic conditions, we conducted an on‐farm study involving 60 wheat fields managed conventionally, under no‐till or organically. We assessed 68 variables defining management, production and soil health properties. We examined how management systems and individual practices describing crop diversification, fertiliser inputs, agrochemical use and soil disturbance influenced production—quantity and quality—and soil health focusing on aspects ranging from soil organic matter over soil structure to microbial abundance and diversity. Our on‐farm comparison showed marked differences between soil health and production in the current system: organic management resulted in the best overall soil health (+47%) but the most significant yield gap (−34%) compared to conventional management. No‐till systems were generally intermediate, exhibiting a smaller yield gap (−17%) and only a marginally improved level of soil health (+5%) compared to conventional management. Yet, the overlap between management systems in production and soil health properties was considerably large. Our results further highlight the importance of soil health for productivity by revealing positive associations between crop yield and soil health properties, particularly under conventional management, whereas factors such as weed pressure were more dominant in organic systems. None of the three systems showed advantages in supporting production‐soil health‐based multifunctionality. In contrast, a cross‐system analysis suggests that multifunctional agroecosystems could be achieved through a combination of crop diversification and organic amendments with effective crop protection. Synthesis and applications: Our on‐farm study implies that current trade‐offs in managing production and soil health could be overcome through more balanced systems incorporating conventional and alternative approaches. Such multifunctionality supporting systems could unlock synergies between vital ecosystem services and help achieve productive yet environmentally sound agriculture supported by healthy soils

Weight Gain in Early Life Predicts Risk of Islet Autoimmunity in Children With a First-Degree Relative With Type 1 Diabetes

OBJECTIVE—In a prospective birth cohort study, we followed infants who had a first-degree relative with type 1 diabetes to investigate the relationship between early growth and infant feeding and the risk of islet autoimmunity

Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial.

Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor. To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma, a fatal disease that commonly recurs at the initial tumor site or in the central nervous system. In this randomized, open-label trial, 695 patients with glioblastoma whose tumor was resected or biopsied and had completed concomitant radiochemotherapy (median time from diagnosis to randomization, 3.8 months) were enrolled at 83 centers (July 2009-2014) and followed up through December 2016. A preliminary report from this trial was published in 2015; this report describes the final analysis. Patients were randomized 2:1 to TTFields plus maintenance temozolomide chemotherapy (n = 466) or temozolomide alone (n = 229). The TTFields, consisting of low-intensity, 200 kHz frequency, alternating electric fields, was delivered (≥ 18 hours/d) via 4 transducer arrays on the shaved scalp and connected to a portable device. Temozolomide was administered to both groups (150-200 mg/m2) for 5 days per 28-day cycle (6-12 cycles). Progression-free survival (tested at α = .046). The secondary end point was overall survival (tested hierarchically at α = .048). Analyses were performed for the intent-to-treat population. Adverse events were compared by group. Of the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]), 637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.52-0.76; P < .001). Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.53-0.76; P < .001). Systemic adverse event frequency was 48% in the TTFields-temozolomide group and 44% in the temozolomide-alone group. Mild to moderate skin toxicity underneath the transducer arrays occurred in 52% of patients who received TTFields-temozolomide vs no patients who received temozolomide alone. In the final analysis of this randomized clinical trial of patients with glioblastoma who had received standard radiochemotherapy, the addition of TTFields to maintenance temozolomide chemotherapy vs maintenance temozolomide alone, resulted in statistically significant improvement in progression-free survival and overall survival. These results are consistent with the previous interim analysis. clinicaltrials.gov Identifier: NCT00916409

Synergism between production and soil health through crop diversification, organic amendments and crop protection in wheat‐based systems

1. One of the critical challenges in agriculture is enhancing yield without compromising its foundation, a healthy environment and, particularly, soils. Hence, there is an urgent need to identify management practices that simultaneously support soil health and production and help achieve environmentally sound production systems. 2. To investigate how management influences production and soil health under realistic agronomic conditions, we conducted an on-farm study involving 60 wheat fields managed conventionally, under no-till or organically. We assessed 68 variables defining management, production and soil health properties. We examined how management systems and individual practices describing crop diversification, fertiliser inputs, agrochemical use and soil disturbance influenced production—quantity and quality—and soil health focusing on aspects ranging from soil organic matter over soil structure to microbial abundance and diversity. 3. Our on-farm comparison showed marked differences between soil health and production in the current system: organic management resulted in the best overall soil health (+47%) but the most significant yield gap (−34%) compared to conventional management. No-till systems were generally intermediate, exhibiting a smaller yield gap (−17%) and only a marginally improved level of soil health (+5%) compared to conventional management. Yet, the overlap between management systems in production and soil health properties was considerably large. 4. Our results further highlight the importance of soil health for productivity by revealing positive associations between crop yield and soil health properties, particularly under conventional management, whereas factors such as weed pressure were more dominant in organic systems. 5. None of the three systems showed advantages in supporting production soil health-based multifunctionality. In contrast, a cross-system analysis suggests that multifunctional agroecosystems could be achieved through a combination of crop diversification and organic amendments with effective crop protection. 6. Synthesis and applications: Our on-farm study implies that current trade-offs in managing production and soil health could be overcome through more balanced systems incorporating conventional and alternative approaches. Such multifunctionality supporting systems could unlock synergies between vital ecosystem services and help achieve productive yet environmentally sound agriculture supported by healthy soils

Multi-objective calibration of RothC using measured carbon stocks and auxiliary data of a long-term experiment in Switzerland

Interactions between model parameters and low spatiotemporal resolution of available data mean that conventional soil organic carbon (SOC) models are often affected by equifinality, with consequent uncertainty in SOC forecasts. Estimation of belowground C inputs is another major source of uncertainty in SOC modelling. Models are usually calibrated on SOC stocks and fluxes from long‐term experiments (LTEs), whereas other point data are not used for constraining the model parameters. We used data from an agricultural long‐term (> 65 years) fertilization experiment to test a multi‐objective parameter estimation approach on the RothC model, combining SOC data from different fertilization treatments with microbial biomass, basal respiration and Zimmermann’s fractions data. We also compared two methods to estimate the belowground C inputs: a conventional scaling of belowground biomass from crop harvest yield and an alternative approach based on constant belowground C for cereals measured experimentally in the field. The resulting posterior parameter distributions still suffered from some equifinality; the most stable C pool kinetic constants and composition of exogenous organic matter were the most sensitive parameters. The use of fixed belowground C inputs for cereals improved the model performance, reducing the importance of treatment‐specific parameters and processes. The introduction of microbial biomass and basal respiration data was effective for increasing determination of the calibration, but also suggested a change in the model structure: the microbial biomass pool, which is proportional to the C inputs in the traditional models, could be represented by different microbial physiology functions

Marizomib for patients with newly diagnosed glioblastoma: a randomized phase 3 trial

Background: Standard treatment for patients with newly diagnosed glioblastoma includes surgery, radiotherapy (RT) and temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). The proteasome has long been considered a promising therapeutic target because of its role as a central biological hub in tumor cells. Marizomib is a novel pan-proteasome inhibitor that crosses the blood brain barrier. Methods: EORTC 1709/CCTG CE.8 was a multicenter, randomized, controlled, open label phase 3 superiority trial. Key eligibility criteria included newly diagnosed glioblastoma, age > 18 years and Karnofsky performance status > 70. Patients were randomized in a 1:1 ratio. The primary objective was to compare overall survival (OS) in patients receiving marizomib in addition to TMZ/RT→TMZ with patients receiving only standard treatment in the whole population, and in the subgroup of patients with MGMT promoter-unmethylated tumors. Results: The trial was opened at 82 institutions in Europe, Canada and the US. A total of 749 patients (99.9% of planned 750) were randomized. OS was not different between the standard and the marizomib arm (median 17 vs 16.5 months; HR=1.04; p=0.64). PFS was not statistically different either (median 6.0 vs. 6.3 months; HR=0.97; p=0.67). In patients with MGMT promoter-unmethylated tumors, OS was also not different between standard therapy and marizomib (median 14.5 vs 15.1 months, HR=1.13; p=0.27). More CTCAE grade 3/4 treatment-emergent adverse events were observed in the marizomib arm than in the standard arm. Conclusions: Adding marizomib to standard temozolomide-based radiochemotherapy resulted in more toxicity, but did not improve OS or PFS in patients with newly diagnosed glioblastoma

Cediranib in addition to chemotherapy for women with relapsed platinum-sensitive ovarian cancer (ICON6): overall survival results of a phase III randomised trial

BACKGROUND: Cediranib, an oral anti-angiogenic VEGFR 1-3 inhibitor, was studied at a daily dose of 20 mg in combination with platinum-based chemotherapy and as maintenance in a randomised trial in patients with first relapse of 'platinum-sensitive' ovarian cancer and has been shown to improve progression-free survival (PFS). PATIENTS AND METHODS: ICON6 (NCT00532194) was an international three-arm, double-blind, placebo-controlled randomised trial. Between December 2007 and December 2011, 456 women were randomised, using stratification, to receive either chemotherapy with placebo throughout (arm A, reference); chemotherapy with concurrent cediranib, followed by maintenance placebo (arm B, concurrent); or chemotherapy with concurrent cediranib, followed by maintenance cediranib (arm C, maintenance). Due to an enforced redesign of the trial in September 2011, the primary endpoint became PFS between arms A and C which we have previously published, and the overall survival (OS) was defined as a secondary endpoint, which is reported here. RESULTS: After a median follow-up of 25.6 months, strong evidence of an effect of concurrent plus maintenance cediranib on PFS was observed [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.44-0.72, P < 0.0001]. In this final update of the survival analysis, 90% of patients have died. There was a 7.4-month difference in median survival and an HR of 0.86 (95% CI: 0.67-1.11, P = 0.24) in favour of arm C. There was strong evidence of a departure from the assumption of non-proportionality using the Grambsch-Therneau test (P = 0.0031), making the HR difficult to interpret. Consequently, the restricted mean survival time (RMST) was used and the estimated difference over 6 years by the RMST was 4.8 months (95% CI: -0.09 to 9.74 months). CONCLUSIONS: Although a statistically significant difference in time to progression was seen, the enforced curtailment in recruitment meant that the secondary analysis of OS was underpowered. The relative reduction in the risk of death of 14% risk of death was not conventionally statistically significant, but this improvement and the increase in the mean survival time in this analysis suggest that cediranib may have worthwhile activity in the treatment of recurrent ovarian cancer and that further research should be undertaken