Office of Regulatory Affairs Strategies for Building an Integrated National Laboratory Network for Food and Feed

An interconnected network of accredited federal, state, local, tribal, and territorial laboratories is critical to ensuring the safety of the U.S. food supply and the development of the Integrated Food Safety System (IFSS). In 2004, as part of a national policy to defend the U.S. food supply against terrorist attacks, major disasters, and other emergencies, the Food Emergency Response Network (FERN) was created to integrate the nation’s multilevel (i.e., federal, state, local, tribal, territorial) food-testing laboratories to detect, identify, respond to, and recover from a bioterrorism act affecting the safety of the food supply, or a public health emergency/outbreak involving the food supply. Since 2004, federal agencies have invested an estimated $200 million in FERN. The majority of this investment has been in the FERN cooperative agreements with FDA and USDA-FSIS investing$95.8 million and $69 million, respectively. FDA has promoted the accreditation of state laboratories through cooperative agreement funding, investing more than$50 million to fund these grants. On November 11, 2014, the Office of Regulatory Affairs (ORA) requested that the FDA Science Board establish a subcommittee to evaluate current investments in: (1) the FERN cooperative agreement funding program (CAP), and (2) funding for state laboratories to achieve International Organization for Standardization (ISO) accreditation. The goal was to ascertain how ORA can advance and establish an effective integrated laboratory network among ORA, FDA Center, and state public health and food- and feed-testing laboratories. In response to this request, the Science Board created the ORA FERN Cooperative Agreement Evaluation Subcommittee on July 1, 2015. This report summarizes the results of the Subcommittee’s review

Use of Gene Editing in USDA Research

The Science Advisory Council was established in FY2016 as a subcommittee of the National Agricultural Research, Extension, Education, and Economics (NAREEE) Advisory Board by the Chief Scientist as a result of recommendations from the 2012 report on Agricultural Preparedness by the President’s Council of Advisors on Science and Technology. The Council\u27s charge is to provide advice and guidance, on a scientific basis, on the overall strength, practicality, and direction of agricultural research, including emerging technology and scientific issues and report any findings publicly to the NAREEE Advisory Board. The USDA Chief Scientist first asked the Council to examine rigor and reproducibility in USDA science. The second was to review the technology of Gene Editing in view of its possible use by USDA to address challenges. The term gene editing or genome editing is a generally considered a type of genetic engineering in which DNA is inserted, deleted or replaced in the genome of a living organism using engineered nucleases, sometimes referred to using a common description of molecular scissors. The nucleases used in this function create breaks in the target locations in the genome. These breaks are repaired leading to specific edits. There are currently a series of engineered nucleases being used to affect these edits. One of the most commonly known is the CRISPR-Cas system. In traditional breeding, a desired phenotype is observed and then if the approach is available, the expense warrants it and the tools are available; the genetic basis for the phenotype is studied and elucidated. In the use of a gene editing approach, a reverse of traditional breeding is done in that a sequence of DNA is modified and a phenotypic response is monitored. In this sense of study, gene editing holds great promise to understand better the role of single genes and their possible effect on a product and to modify them for improved human value. Gene editing is a tool to be used by molecular researchers, hopefully in consultations with breeders, to enhance the search for improved products and solutions. It joins many other tools used by USDA scientists such as selective breeding, cross breeding, marker assisted selection / genomic selection, etc. to improve agricultural production, sustainability and health

Temporary Restoration of Bull Trout Passage at Albeni Falls Dam

This study was designed to monitor movements of bull trout that were provided passage above Albeni Falls Dam, Pend Oreille River. Electrofishing and angling were used to collect bull trout below the dam. Tissue samples were collected from each bull trout and sent to the U. S. Fish and Wildlife Service Abernathy Fish Technology Center Conservation Genetics Lab, Washington. The DNA extracted from tissue samples were compared to a catalog of bull trout population DNA from the Priest River drainage, Lake Pend Oreille tributaries, and the Clark Fork drainage to determine the most probable tributary of origin. A combined acoustic radio or radio tag was implanted in each fish prior to being transported and released above the dam. Bull trout relocated above the dam were able to volitionally migrate into their natal tributary, drop back downstream, or migrate upstream to the next dam. A combination of stationary radio receiving stations and tracking via aircraft, boat, and vehicle were used to monitor the movement of tagged fish to determine if the spawning tributary it selected matched the tributary assigned from the genetic analysis. Seven bull trout were captured during electrofishing surveys in 2008. Of these seven, four were tagged and relocated above the dam. Two were tagged and left below the dam as part of a study monitoring movements below the dam. One was immature and too small at the time of capture to implant a tracking tag. All four fish released above the dam passed by stationary receivers stations leading into Lake Pend Oreille and no fish dropped back below the dam. One of the radio tags was recovered in the tributary corresponding with the results of the genetic test. Another fish was located in the vicinity of its assigned tributary, which was impassable due to low water discharge at its mouth. Two fish have not been located since entering the lake. Of these fish, one was immature and not expected to enter its natal tributary in the fall of 2008. The other fish was large enough to be mature, but at the time of capture its sex was unable to be determined, indicating it may not have been mature at the time of capture. These fish are expected to enter their natal tributaries in early summer or fall of 2009

Report and Recommendations of the Balance of Crop Research Working Group of the National Agricultural Research, Extension, Education and Economics (NAREEE) Advisory Board

In December of 2012, the President’s Council of Advisors on Science & Technology (PCAST) issued a report to the President on Agricultural Preparedness and the Agriculture Research Enterprise. The PCAST report recognizes the long-term history of public investment in agricultural research. The report also recognized significant private investment into agricultural research. Significantly, the report is adamant that the agricultural research enterprise is not prepared to meet the challenges of the 21st century. The report cited two reasons: too little competitive research and an imbalance of research priorities between private and public funding sources. This report addresses the latter issue. Members of the PCAST met with the National Agricultural Research, Extension, Education, and Economics (NAREEE) Advisory Board during a formal meeting held on May 28-30, 2013. Subsequently, the NAREEE Advisory Board received a formal request by the USDA Office of the Chief Scientist that requested advice regarding the PCAST report calling for a re-balancing of research between public and private sources. This report is the culmination of these discussions in addition to discussion amongst the working group members, a thorough review of the PCAST report, and the review of information provided by the Economic Research Service. The intent of this report is to guide USDA in its review and actions to address the PCAST concern over imbalance – public versus private funding of agricultural research. Our intent is not to solve this issue in this report

Agricultural Conservation Planning Framework: 1. Developing Multipractice Watershed Planning Scenarios and Assessing Nutrient Reduction Potential

Spatial data on soils, land use, and topography, combined with knowledge of conservation effectiveness, can be used to identify alternatives to reduce nutrient discharge from small (hydrologic unit code [HUC]12) watersheds. Databases comprising soil attributes, agricultural land use, and light detection and ranging–derived elevation models were developed for two glaciated midwestern HUC12 watersheds: Iowa’s Beaver Creek watershed has an older dissected landscape, and Lime Creek in Illinois is young and less dissected. Subsurface drainage is common in both watersheds. We identified locations for conservation practices, including in-field practices (grassed waterways), edge-of-field practices (nutrient-removal wetlands, saturated buffers), and drainage-water management, by applying terrain analyses, geographic criteria, and cross-classifications to field- and watershed-scale geographic data. Cover crops were randomly distributed to fields without geographic prioritization. A set of alternative planning scenarios was developed to represent a variety of extents of implementation among these practices. The scenarios were assessed for nutrient reduction potential using a spreadsheet approach to calculate the average nutrient-removal efficiency required among the practices included in each scenario to achieve a 40% NO3–N reduction. Results were evaluated in the context of the Iowa Nutrient Reduction Strategy, which reviewed nutrient-removal efficiencies of practices and established the 40% NO3–N reduction as Iowa’s target for Gulf of Mexico hypoxia mitigation by agriculture. In both test watersheds, planning scenarios that could potentially achieve the targeted NO3–N reduction but remov

Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif

MicroRNAs modulate tumorigenesis through suppression of specific genes. As many tumour types rely on overlapping oncogenic pathways, a core set of microRNAs may exist, which consistently drives or suppresses tumorigenesis in many cancer types. Here we integrate The Cancer Genome Atlas (TCGA) pan-cancer data set with a microRNA target atlas composed of publicly available Argonaute Crosslinking Immunoprecipitation (AGO-CLIP) data to identify pan-tumour microRNA drivers of cancer. Through this analysis, we show a pan-cancer, coregulated oncogenic microRNA ‘superfamily’ consisting of the miR-17, miR-19, miR-130, miR-93, miR-18, miR-455 and miR-210 seed families, which cotargets critical tumour suppressors via a central GUGC core motif. We subsequently define mutations in microRNA target sites using the AGO-CLIP microRNA target atlas and TCGA exome-sequencing data. These combined analyses identify pan-cancer oncogenic cotargeting of the phosphoinositide 3-kinase, TGFβ and p53 pathways by the miR-17-19-130 superfamily members

Immunogenicity and seroefficacy of 10-valent and 13-valent pneumococcal conjugate vaccines: a systematic review and network meta-analysis of individual participant data

Background: Vaccination of infants with pneumococcal conjugate vaccines (PCV) is recommended by the World Health Organization. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines. Methods: In this systematic-review and network meta-analysis, we searched the Cochrane Library, Embase, Global Health, Medline, clinicaltrials.gov and trialsearch.who.int up to February 17, 2023 with no language restrictions. Studies were eligible if they presented data comparing the immunogenicity of either PCV7, PCV10 or PCV13 in head-to-head randomised trials of young children under 2 years of age, and provided immunogenicity data for at least one time point after the primary vaccination series or the booster dose. Publication bias was assessed via Cochrane's Risk Of Bias due to Missing Evidence tool and comparison-adjusted funnel plots with Egger's test. Individual participant level data were requested from publication authors and/or relevant vaccine manufacturers. Outcomes included the geometric mean ratio (GMR) of serotype-specific IgG and the relative risk (RR) of seroinfection. Seroinfection was defined for each individual as a rise in antibody between the post-primary vaccination series time point and the booster dose, evidence of presumed subclinical infection. Seroefficacy was defined as the RR of seroinfection. We also estimated the relationship between the GMR of IgG one month after priming and the RR of seroinfection by the time of the booster dose. The protocol is registered with PROSPERO, ID CRD42019124580. Findings: 47 studies were eligible from 38 countries across six continents. 28 and 12 studies with data available were included in immunogenicity and seroefficacy analyses, respectively. GMRs comparing PCV13 vs PCV10 favoured PCV13 for serotypes 4, 9V, and 23F at 1 month after primary vaccination series, with 1.14- to 1.54- fold significantly higher IgG responses with PCV13. Risk of seroinfection prior to the time of booster dose was lower for PCV13 for serotype 4, 6B, 9V, 18C and 23F than for PCV10. Significant heterogeneity and inconsistency were present for most serotypes and for both outcomes. Two-fold higher antibody after primary vaccination was associated with a 54% decrease in risk of seroinfection (RR 0.46, 95% CI 0.23–0.96). Interpretation: Serotype-specific differences were found in immunogenicity and seroefficacy between PCV13 and PCV10. Higher antibody response after vaccination was associated with a lower risk of subsequent infection. These findings could be used to compare PCVs and optimise vaccination strategies. Funding: The NIHR Health Technology Assessment Programme