Transition pathways to sustainable agricultural water management: A review of integrated modeling approaches

Agricultural water management (AWM) is an interdisciplinary concern, cutting across traditional domains such as agronomy, climatology, geology, economics, and sociology. Each of these disciplines has developed numerous process-based and empirical models for AWM. However, models that simulate all major hydrologic, water quality, and crop growth processes in agricultural systems are still lacking. As computers become more powerful, more researchers are choosing to integrate existing models to account for these major processes rather than building new cross-disciplinary models. Model integration carries the hope that, as in a real system, the sum of the model will be greater than the parts. However, models based upon simplified and unrealistic assumptions of physical or empirical processes can generate misleading results which are not useful for informing policy. In this article, we use literature and case studies from the High Plains Aquifer and Southeastern United States regions to elucidate the challenges and opportunities associated with integrated modeling for AWM and recommend conditions in which to use integrated models. Additionally, we examine the potential contributions of integrated modeling to AWM - the actual practice of conserving water while maximizing productivity. Editor's note: This paper is part of the featured series on Optimizing Ogallala Aquifer Water Use to Sustain Food Systems. See the February 2019 issue for the introduction and background to the series.Peer reviewedPlant and Soil Science

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Deficit Irrigation Management of Maize in the High Plains Aquifer Region: A Review

Irrigated agriculture is a major economic contributor of the High Plains Region and it primarily relies on the High Plains Aquifer as a source of water. Over time, areas of the High Plains Aquifer have experienced drawdowns limiting its ability to supply sufficient water to sustain fully irrigated crop production. This among other reasons, including variable climatic factors and differences in state water policy, has resulted in some areas adopting and practicing deficit irrigation management. Considerable research has been conducted across the High Plains Aquifer region to identify locally appropriate deficit irrigation strategies. This review summarizes and discusses research conducted in Nebraska, Colorado, Kansas, and Texas, as well as highlights areas for future research. Editor’s note: This paper is part of the featured series on Optimizing Ogallala Aquifer Water Use to Sustain Food Systems. See the February 2019 issue for the introduction and background to the series

Use of Multiple Environment Variety Trials Data to Simulate Maize Yields in the Ogallala Aquifer Region: A Two Model Approach

With a long-term goal to optimize use of groundwater in the Ogallala Aquifer Region (OAR) to sustain food production systems, this study was conducted to calibrate Decision Support System for Agrotechnology Transfer (DSSAT) and AquaCrop crop modeling platforms to simulate maize production at a regional scale using historic datasets. Calibration of the models with local crop growth data and crop management practices is important, but usually this in-season crop growth information is not available. This study determined the possibility of using maize variety trial data for the evaluation of the CSM-Crop Estimation through Resources and Environmental Synthesis-Maize and AquaCrop models in the OAR. The models were calibrated and tested in three counties in Nebraska. Both the models were then used to simulate irrigated maize yield during 1988 to 2015 for all three counties. The criteria for evaluating the performance of these crop models included statistical parameters and graphical analysis. The performance of both models were then compared with the observed yield from field variety test results and historic National Agricultural Statistical Service yields. The results indicated that difference between yield of calibrated DSSAT model and observed yield was less than 10% and AquaCrop root mean square error ranged from 740 to 1,820 kg/ha. Long-term comparison between observed and simulated Nebraska county yields also indicated confidence in calibrating crop models with typical end of season yield data and using these models for studying crop production at regional scales when detailed in-season crop growth observed data are not available