International Testing Guidelines Research Articles

Comparative Analysis of Domestic and International Test Guidelines for Various Concrete Repair Materials

The number of aged bridges among concrete structures is increasing. Therefore, to increase their lifespans, repair and reinforcement schemes ought to be implemented. This study selected various repair materials according to crack-surface treatment, crack-filling, and crack-injection methods. These repair materials were evaluated using various test methods proposed by the Korean Standards and the American Society for Testing and Materials for structure protection, structure restoration, and crack repair; the results were analyzed and compared. Consequently, the structure restoration material exhibited a similar freezing–thawing trend as that of chloride, while also exhibiting similar flexural, compressive, bond, and splitting-tensile strengths. However, chloride yielded performance differences (up to two-fold) depending on the type of material used for comparison. The crack-repair material yielded similar trends only for bond strength but yielded differences (up to 2–4-fold) in tensile, compressive, and flexural strengths depending on the material used for comparison. These results confirmed that crack-repair materials exhibit significant differences in performance depending on the manufacturer compared with structure protection and structure restoration materials. Therefore, it is expected that repair materials appropriate for usability, durability, and structure safety, while also being environmentally friendly, could be used in future bridge repairs based on these test evaluations.

Abstract PS8-14: Pathogenic variants in hereditary cancer syndrome genes are prevalent among breast cancer patients not meeting various ex-U.S. genetic testing guidelines

Abstract Background:Therapeutic and risk management options have expanded for patients harboring pathogenic variants (PVs) in cancer predisposition genes. Historically, testing costs and clinical implementation challenges led to restrictive testing guidelines in many countries. Increasing evidence demonstrates that narrow criteria will miss patients with potentially actionable PVs and broader testing is a cost-effective way to identify patients (and their family members) with PVs. Here we assess the efficacy of multiple international testing guidelines in identifying breast cancer patients with clinically actionable PVs. Methods:We reanalyzed a prospective cohort of breast cancer (BC) patients referred by their providers for multigene germline genetic testing (PMID: 30526229) 50% of which met U.S. testing criteria, by design. The is a cohort of U.S.-based patients, primarily Caucasian of Northern European ancestry. We applied testing guidelines from Australia, U.K. and 2 Canadian provinces (Ontario, British Columbia) to this cohort to determine their efficacy in selecting patients with PVs. These countries were chosen because of their single-payer healthcare model and their similar ethnic distribution to the U.S. Analysis focused on yield of PVs in high risk (>4x risk compared to general population) breast/ovarian (BC/OV) cancer genes. Results:Table 1 displays the distribution of in criteria (IC) vs. out of criteria (OOC) patients by country/testing criteria. Over 75% of patients in each country/province analyzed were OOC. Rates of PVs were similar between IC and OOC patients across countries. Existing Canadian, Australian and U.K. criteria missed up to 30% of patients with high risk PVs (Table 1). The majority (>80%) of PVs in OOC patients were in genes with published management guidelines. Conclusions:In our cohort, select ex-U.S. testing criteria identified <30% of patients with PVs, while almost half of OOC patients harbored clinically relevant, potentially actionable mutations. These data suggest expanding certain international testing criteria would allow better identification and improved management for many patients diagnosed with breast cancer across the globe, and their families via cascade testing. This study also suggests additional research is needed to evaluate the efficacy of additional provincial and international criteria, including cost-effectiveness analyses, to inform future guideline updates. Table 1. Findings in IC vs. OOC patientsOverallIn criteria Out of criteriaCountry/providenceGuidelineTotal n of cohortIC (% of total cohort)OOC (% of total cohort)Total PV IC (% of IC cohort)Total PV OOC (% of OOC cohort)High risk^ PVs (% of total PVs)High risk^ PVs (% of total PVs)U.S.NCCN953473 (49.6)480 (50.4)43 (9.1)40 (8.3)22 (26.5)8 (9.6)OntarioMOHLTC953210 (22.0)743 (78.0)18 (8.6)65 (8.7)5 (6.0)25 (30.1)B.C.BCHCP953203 (21.3)750 (78.7)24 (11.8)59 (7.9)9 (10.8)19 (22.9)AustraliaeviQ953180 (18.9)773 (81.1)19 (10.6)64 (8.3)12 (14.5)18 (21.7)U.K.NICE*826**127 (14.7)736 (85.3)11 (8.7)64 (8.7)6 (7.2)22 (26.5)US, United States; B.C., British Columbia; UK, United KingdomNCCN, National Comprehensive Cancer Network v. 2017MOHLTC, Ministry of Health and Long Term Care BCHCP, BC Provincial Health Services Authority Hereditary Cancer Program NICE, National Institute for Health Care Excellence*testing eligibility requires >10% BRCA mutation detection rate, typically assessed by BOADICEA model in the UK but for this cohort risk estimates were only available via BRCAPro ** BRCAPro scores were not available for the full cohort ^Includes BRCA1, BRCA2, PALB2, TP53, RAD51C, RAD51D, MSH6 Citation Format: Sarah M Nielsen, Peter Beitsch, Pat Whitworth, Emily Decker, Natalie Rickers, Hana Sroka, Alekhya Narravula, Ed D Esplin, Robert L. Nussbaum. Pathogenic variants in hereditary cancer syndrome genes are prevalent among breast cancer patients not meeting various ex-U.S. genetic testing guidelines [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-14.

Extending international toxicity testing guidance to middle eastern test species.

The Arabian Gulf is a dynamic environment with unique habitats located in the Middle East. The inhabitants of this ecosystem have historically been understudied and a lack of reliable toxicity data exists to benchmark their sensitivities. Current international testing guidelines (i.e. Organization for Economic Co-Operation and Development (OECD), International Standard Organization (ISO), Environmental Protection Agency (EPA), etc.) do not reference relevant species for this region of the world. This research focuses on developing standard test conditions for relevant test organisms indigenous to the Middle East region while maintaining general agreement with international testing guidelines. A copepod, cyanobacteria and juvenile killifish were selected as local test organisms to perform acute exposures to 4 Aromatic Hydrocarbons (AHs) ranging in log KOW from 3.88-5.19, 1-methylnaphthalene, phenanthrene, biphenyl and octahydrophenanthrene. Acute test durations were 48, 72 and 96h and generally followed ISO 14669, OECD 201 and 203 for the copepod, algae and killifish respectively. To deliver and maintain controlled exposure concentrations, a passive dosing (PD) format was employed. PD effectively maintained aqueous exposure concentration of the AHs tested over the test duration. Effects data were comparable to literature values for similar taxonomic groupings. Critical target lipid body burden's for test species used were calculated and found to be in agreement with those predicted by the Target Lipid Model.

Two dynamic energy budget models for the harpacticoid copepod Nitocra spinipes

The harpacticoid copepod Nitocra spinipes is a commonly used test species in ecotoxicological studies and subject of multiple international testing guidelines. While we strive for a better understanding of toxicant-induced effects in this species, physiological models rooted in the Dynamic Energy Budget (DEB) theory can help to explain such effects on the level of energy allocations within the organism. In previous works that aimed to capture the copepod life history in a DEB model, diverging assumptions on the growth pattern of copepods were made. While some authors presumed von Bertalanffy growth, others presumed an upcurving in length versus time due to metabolic acceleration. In this study we parametrized the two typified DEB models “abp” (metabolic acceleration from birth to puberty) and “sbp” (standard von Bertalanffy growth from birth to puberty) on life history data of N. spinipes. Besides using data from literature, we also measured additional length-at-time data to aid the parameter estimation. As the body proportions of N. spinipes changed continuously throughout its development, we used the square root of the top view area as a length measure to scale with the cube root of structural volume in length-to-volume conversions. Experimental data were predicted well with both models according to goodness of fit criteria. Despite a slightly better data fit in abp, we cannot rule out sbp as implausible. Overall, we expect both models to perform equally well in future applications. More detailed data on N. spinipes and closely related species are needed to support or reject the presumption of metabolic acceleration in the life history of copepods.

Antibiotic Resistance among Clinical Ureaplasma Isolates Recovered from Neonates in England and Wales between 2007 and 2013.

Ureaplasma spp. are associated with numerous clinical sequelae with treatment options being limited due to patient and pathogen factors. This report examines the prevalence and mechanisms of antibiotic resistance among clinical strains isolated from 95 neonates, 32 women attending a sexual health clinic, and 3 patients under investigation for immunological disorders, between 2007 and 2013 in England and Wales. MICs were determined by using broth microdilution assays, and a subset of isolates were compared using the broth microdilution method and the Mycoplasma IST2 assay. The underlying molecular mechanisms for resistance were determined for all resistant isolates. Three isolates carried the tet(M) tetracycline resistance gene (2.3%; confidence interval [CI], 0.49 to 6.86%); two isolates were ciprofloxacin resistant (1.5%; CI, 0.07 to 5.79%) but sensitive to levofloxacin and moxifloxacin, while no resistance was seen to any macrolides tested. The MIC values for chloramphenicol were universally low (2 μg/ml), while inherently high-level MIC values for gentamicin were seen (44 to 66 μg/ml). The Mycoplasma IST2 assay identified a number of false positives for ciprofloxacin resistance, as the method does not conform to international testing guidelines. While antibiotic resistance among Ureaplasma isolates remains low, continued surveillance is essential to monitor trends and threats from importation of resistant clones.

ICCVAM: Birnbaum and Stokes Respond

ICCVAM: Birnbaum and Stokes Respond

The chironomid acute toxicity test: Development of a new test system

This paper describes the basis for a water-only acute chironomid toxicity test guideline using first-instar larvae. The method is based on the OECD test guidelines for the acute Daphnia sp. immobilization test and the long-term tests with Chironomus sp., reflecting the common test procedures currently used by the European agrochemical industry. Development of this guideline proposal is important under the European Plant Protection Products Directive (91/414/EEC), under which an insect species may be required to be tested, particularly for certain insecticides, for which Daphnia sp. may not be representative of the sensitivity of nontarget aquatic invertebrates. Chironomus sp. is a freshwater insect currently used in different international test guidelines. Because their ready availability as a test organism, with culturing conditions and certain test methods already established, Chironomus sp. is regarded as a suitable additional freshwater invertebrate species for regulatory testing.