Identifying opportunities for high resolution pesticide usage data to improve the efficiency of endangered species pesticide risk assessment.

The US pesticide registration and review process requires regular re-assessment of the risk of pesticide use to species listed under the Endangered Species Act (ESA), yet current assessment methods are inefficient when applied to hundreds of pesticides potentially impacting multiple species across a continent. Thus, many pesticides remain on the market without complete review. We assessed the value of using high resolution pesticide usage data in the risk assessment process to rapidly improve process efficiency. By using data available only in California, we found that high resolution data increased the number of species deemed not likely to be adversely affected by pesticides from <5 % to nearly 50 %. Across the contiguous US, we predicted that 48 % of species would be deemed not likely to be adversely affected using high resolution data, compared to 20 % without. However, if such data were available in just 11 states, 68 % of the available gains in efficiency could be obtained. Overall, using existing high-resolution data in California and a focused collection of such information from 11 other states could reduce risk assessment burden across the contiguous U.S. by one-quarter.

Prioritizing resource allocation to reduce adverse effects of pesticide risk for endangered species.

The use of pesticides promotes food security because of the multiple benefits it brings to agriculture, such as reduction in crop losses. However, the use of pesticides can be potentially harmful to non-target species. In the U.S., the Environmental Protection Agency regulates the use of pesticides to manage the risks associated with these agents and to protect species under the Endangered Species Act. As part of these regulations, pesticides must be registered and then reviewed every 15 years to ensure the use conditions are updated with the best available data. The registration and review process can invoke corrective measures to ensure protection of endangered species. However, the registration review process is highly resource and time consuming. There is currently a backlog of unreviewed pesticides, leaving a large quantity of pesticides without updated use conditions to protect species. Identifying ways to streamline this process is urgently needed. We develop a sequencing approach to address the risk assessment bottleneck in the pesticide registration and review process and identify species that would benefit most from detailed assessments. We then demonstrate the magnitude of potential efficiencies using this sequencing process for 61 terrestrial listed species in the state of California. Our results show a consistent ranking of listed species according to their relative benefits from assessment, with 90 % of the species being robustly classified across scenarios in the sensitivity analysis. We found that prioritizing the assessment of a small group of species could potentially result in high conservation benefits, and identify species in need of more detailed data for a robust sequencing. We examine how a sequencing approach can guide decisions about what species might benefit most from different levels of assessment. Our results demonstrate the conservation benefits of employing a sequencing approach to prioritize the allocation of limited resources for endangered species.

Divergent climate change effects on widespread dryland plant communities driven by climatic and ecohydrological gradients.

Plant community response to climate change will be influenced by individual plant responses that emerge from competition for limiting resources that fluctuate through time and vary across space. Projecting these responses requires an approach that integrates environmental conditions and species interactions that result from future climatic variability. Dryland plant communities are being substantially affected by climate change because their structure and function are closely tied to precipitation and temperature, yet impacts vary substantially due to environmental heterogeneity, especially in topographically complex regions. Here, we quantified the effects of climate change on big sagebrush (Artemisia tridentata Nutt.) plant communities that span 76 million ha in the western United States. We used an individual-based plant simulation model that represents intra- and inter-specific competition for water availability, which is represented by a process-based soil water balance model. For dominant plant functional types, we quantified changes in biomass and characterized agreement among 52 future climate scenarios. We then used a multivariate matching algorithm to generate fine-scale interpolated surfaces of functional type biomass for our study area. Results suggest geographically divergent responses of big sagebrush to climate change (changes in biomass of -20% to +27%), declines in perennial C3 grass and perennial forb biomass in most sites, and widespread, consistent, and sometimes large increases in perennial C4 grasses. The largest declines in big sagebrush, perennial C3 grass and perennial forb biomass were simulated in warm, dry sites. In contrast, we simulated no change or increases in functional type biomass in cold, moist sites. There was high agreement among climate scenarios on climate change impacts to functional type biomass, except for big sagebrush. Collectively, these results suggest divergent responses to warming in moisture-limited versus temperature-limited sites and potential shifts in the relative importance of some of the dominant functional types that result from competition for limiting resources.

Exogenous RNA as a Regulatory Signal during a Plant's Interaction with the Biotic Environment: An Evolutionary Perspective and Future Applications in Agriculture.

Environmental RNAi (eRNAi) is a sequence-specific regulation of endogenous gene expression in a responsive organism by exogenous RNA. While exogenous RNA transfer between organisms of different kingdoms of life have been unambiguously identified in nature, our understanding of the biological significance of this phenomenon remains obscure, particularly within an evolutionary context. During the last decade multiple reports utilizing various mechanisms of natural eRNAi phenomena have been attempted to develop new agricultural traits and products including weed, disease and insect control. Although these attempts yielded mixed results, this concept remains extremely attractive for many agricultural applications. To better utilize eRNAi for practical applications, we would like to emphasize the necessity of understanding the biological significance of this phenomenon within an evolutionary context and learn from nature by developing advanced tools to identify and study new cases of exogeneous RNA transfer and eRNAi. In this opinion article we would like to look at the exogeneous RNA transfer from an evolutionary perspective, propose that new cases of exogeneous RNA transfer still remain to be identified in nature, and address a knowledge gap in understanding the biological function and significance of RNA transfer. We believe such approach may eventually result in a more successful use of this phenomenon for practical applications in agriculture.

Environmental Fate and Dissipation of Applied dsRNA in Soil, Aquatic Systems, and Plants.

Two primary use patterns exist for dsRNA-based products for crop protection: in planta produced dsRNA such as in a genetically engineered (GE) crop; and topically applied dsRNA such as a spray application. To enable effective environmental risk assessments for these products, dsRNA must be successfully measured in relevant environmental compartments (soil, sediment, surface water) to provide information on potential exposure. This perspective reviews results from numerous environmental fate and degradation studies with topically applied unformulated dsRNAs to demonstrate the high lability of these molecules and low potential for persistence in the environment. Additionally, we report on results of a pilot study of topically applied dsRNA on soybean plants demonstrating similar rapid degradation under field conditions. Microbial degradation of nucleic acids in environmental compartments has been shown to be a key driver for this lack of persistence. In fact, the instability of dsRNA in the environment has posed a challenge for the development of commercial topically-applied products. Formulations or other approaches that mitigate environmental degradation may lead to development of commercially successful products but may change the known degradation kinetics of dsRNAs. The formulation of these products and the resultant impacts on the stability of the dsRNA in environmental compartments will need to be addressed using problem formulation and product formulation testing may be required on a case by case basis to ensure an effective risk assessment.

Broccoli Sprouts Delay Prostate Cancer Formation and Decrease Prostate Cancer Severity with a Concurrent Decrease in HDAC3 Protein Expression in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice.

BACKGROUND: Cruciferous vegetables have been associated with the chemoprevention of cancer. Epigenetic regulators have been identified as important targets for prostate cancer chemoprevention. Treatment of human prostate cancer cells with sulforaphane (SFN), a chemical from broccoli and broccoli sprouts, inhibits epigenetic regulators such as histone deacetylase (HDAC) enzymes, but it is not known whether consumption of a diet high in broccoli sprouts impacts epigenetic mechanisms in an in vivo model of prostate cancer. OBJECTIVE: In the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, we tested the hypothesis that a broccoli sprout diet suppresses prostate cancer, inhibits HDAC expression, alters histone modifications, and changes the expression of genes regulated by HDACs. METHODS: TRAMP mice were fed a 15% broccoli sprout or control AIN93G diet; tissue samples were collected at 12 and 28 wk of age. RESULTS: Mice fed broccoli sprouts had detectable amounts of SFN metabolites in liver, kidney, colon, and prostate tissues. Broccoli sprouts reduced prostate cancer incidence and progression to invasive cancer by 11- and 2.4-fold at 12 and 28 wk of age, respectively. There was a significant decline in HDAC3 protein expression in the epithelial cells of prostate ventral and anterior lobes at age 12 wk. Broccoli sprout consumption also decreased histone H3 lysine 9 trimethylation in the ventral lobe (age 12 wk), and decreased histone H3 lysine 18 acetylation in all prostate lobes (age 28 wk). A decline in p16 mRNA levels, a gene regulated by HDAC3, was associated with broccoli sprout consumption, but no significant changes were noted at the protein level. CONCLUSIONS: Broccoli sprout intake was associated with a decline in prostate cancer occurrence and HDAC3 protein expression in the prostate, extending prior work that implicated loss of HDAC3/ corepressor interactions as a key preventive mechanism by SFN in vivo.

Disparities in CD4+ T-Lymphocyte Monitoring Among Human Immunodeficiency Virus-Positive Medicaid Beneficiaries: Evidence of Differential Treatment at the Point of Care.

BACKGROUND: Monitoring of immune function, measured by CD4 cell count, is an essential service for people with Human Immunodeficiency Virus (HIV). Prescription of antiretroviral (ARV) medications is contingent on CD4 cell count; patients without regular CD4 monitoring are unlikely to receive ARVs when indicated. This study assesses disparities in CD4 monitoring among HIV-positive Medicaid beneficiaries. METHODS: In this retrospective observational study, we examined 24 months of administrative data on 2,250 HIV-positive, continuously-enrolled fee-for-service Medicaid beneficiaries with at least two outpatient healthcare encounters. We used logistic regression to evaluate the association of patient demographics (age, gender, race/ethnicity, and language) with receipt of at least one CD4 test per year, controlling for other potentially confounding variables. RESULTS: Having a history of ARV therapy was positively associated with receipt of CD4 tests. We found racial/ethnic, gender, and age disparities in CD4 testing. Among individuals with a history of ARV use, all racial/ethnic groups were significantly less likely to have CD4 tests than White non-Latinos (African Americans, OR = 0.35, p<0.0001; Asian/Pacific Islanders, OR = 0.31, p=0.0047; and, Latinos, OR = 0.42, p<0.0001). CONCLUSIONS: Disparities in receipt of CD4 tests elucidate one potential pathway for previously reported disparities in ARV treatment. Further qualitative and quantitative research is needed to identify the specific factors that account for these disparities, so that appropriate interventions can be implemented.

Proposed regulations could limit access to affordable health coverage for workers' children and family members.

Key Findings. The Patient Protection and Affordable Care Act (ACA) is designed to offer premium subsidies to help eligible individuals and their families purchase insurance coverage when affordable job-based coverage is not available. However, the law is unclear on how this affordability protection is applied in those instances where self-only coverage offered by an employer is affordable but family coverage is not. Regulations recently proposed by the Department of the Treasury would make family members ineligible for subsidized coverage in the exchange if an employee is offered affordable self-only coverage by an employer, even if family coverage is unaffordable. This could have significant financial consequences for low- and moderate-income families that fall in this gap. Using an alternative interpretation of the law could allow the entire family to enter the exchange when family coverage is unaffordable, which would broaden access to coverage. However, this option has been cited as cost prohibitive. In this brief we consider a middle ground alternative that would base eligibility for the individual worker on the cost of self-only coverage, but would use the additional cost to the employee for family coverage as the basis for determining affordability and eligibility for subsidies for the remaining family members. We find that: Under the middle ground alternative scenario an additional 144,000 Californians would qualify for and use premium subsidies in the California Health Benefit Exchange, half of whom are children. Less than 1 percent of those with employer-based coverage would move to subsidized coverage in the California Health Benefit Exchange as a result of having unaffordable coverage on the job.