Testing Guidelines Research Articles

P20-05 Polymer REACh on the horizon: technical challenges with polymer materials in several OECD test guideline methods addressing effects on human health and on biotic systems

P20-05 Polymer REACh on the horizon: technical challenges with polymer materials in several OECD test guideline methods addressing effects on human health and on biotic systems

Clinical effectiveness of genetic testing guidelines in patients with thoracic aortic aneurysms

ObjectiveTo analyze the effectiveness of the current genetic testing guidelines for patients with thoracic aortic aneurysms. MethodsWe evaluated genetic tests for thoracic aortic disease (TAD) from 2012 to 2023 in patients aged 18 and older with a thoracic aorta diameter greater than 4 cm. Mutation rates were compared by American College of Cardiology/American Heart Association testing criteria met by patients: age younger than 60 years, syndromic features of connective tissue diseases (CTDs), family history, or none. Results were classified as pathogenic, variants of uncertain significance (VUS), or negative. Genes tested were analyzed in 2 categories: primary (strongly associated with heritable diseases) or secondary (less strongly associated). ResultsIn total, 1034 patients were included: 42.4% aged younger than 60 years, 19.1% with syndromic features of CTD, 41.8% with family history, and 30.7% meeting no criteria. Overall, 3.97% had pathogenic mutations, and 27.27% had VUS. Mutation rates were greatest in patients with syndromic features of CTD (13.2%), followed by patients aged younger than 60 years (5.48%), with a family history (4.63%), and with no criteria met (2.21%). Primary genes had pathogenic mutation rates of 3.29% and VUS rates of 12.19%. Secondary genes had lower pathogenic rates (0.68%) but greater VUS (17.5%). Mutation rates in primary genes peaked at 22% in patients meeting all criteria, whereas those younger than 60 years without family history or syndromic features of CTD had the lowest rate (0.54%). ConclusionsRefining genetic testing guidelines to incorporate multiple patient criteria could enhance risk stratification and support informed decision-making in genetic testing for TAD. Limiting testing to genes strongly associated with TAD could lower VUS rates.

A Systematic Analysis of Read-Across Adaptations in Testing Proposal Evaluations by the European Chemicals Agency.

An important element of the European Union's "Registration, Evaluation, Authorisation and Restriction of Chemicals" (REACH) regulation is the evaluation by the European Chemicals Agency (ECHA) of testing proposals submitted by the registrants to address data gaps in standard REACH information requirements. The registrants may propose adaptations, and ECHA evaluates the reasoning and issues a written decision. Read-across is a common adaptation type, yet it is widely assumed that ECHA often does not agree that the justifications are adequate to waive standard testing requirements. From 2008 to August 2023, a total of 2,630 Testing Proposals were submitted to ECHA; of these, 1,538 had published decisions that were systematically evaluated in this study. Each document was manually reviewed, and information extracted for further analyses. Read-across hypotheses were standardized into 17 assessment elements (AEs); each submission was classified as to the AEs relied upon by the registrants and by ECHA. Data was analyzed for patterns and associations. Testing Proposal Evaluations (TPEs) with adaptations comprised 23% (353) of the total; analogue (168) or group (136) read-across adaptations were most common. Of 304 read-across-containing TPEs, 49% were accepted; the odds of acceptance were significantly greater for group read-across submissions. The data was analyzed by Annex (i.e., tonnage), test guideline study, read-across hypothesis AEs, as well as target and source substance types and their structural similarity. While most ECHA decisions with both positive and negative decisions on whether the proposed read-across was adequate were context-specific, a number of significant associations were identified that influence the odds of acceptance. Overall, this analysis provides an unbiased overview of 15 years of experience with testing proposal-specific read-across adaptations by both registrants and ECHA. These data will inform future submissions as they identify most critical AEs to increase the odds of read-across acceptance.

Tensile testing of S690QL1 HSS welded joint heterogeneous zones using small scale specimens and indentation methods

Abstract The welded joints are structures with significant heterogeneity, indicated by their fundamental segmentation into base metal (BM), heat affected zone (HAZ), and weld metal (WM). The heat affected zone, having width in millimeter scale for fusion welding processes, is further segmented into several characteristic regions, having differences in grain structure and size. The microstructural heterogeneity results in significant differences in mechanical properties of individual welded joint zones. Mechanical testing of such small material volumes is inconvenient, or even impossible, using the standard size specimens proposed in testing standards. Requirement to precisely position the specimens, even ones with subsize dimensions, and investigate mechanical properties of specific narrow HAZ regions presents certain challenge. This work investigates the X welded joint of S690QL1 grade high strength steel (HSS), welded with slightly overmatching filler metal. The material tensile properties are tested, using small scale specimens and indentation methods. Small scale specimens are ASTM E8 round tensile subsize and flat sheet mini tensile specimens (MTS). The indentation methods include hardness testing and profilometry-based indentation plastometry (PIP) method, to gain additional insights into material stress–strain behavior. Finally, paper evaluates the testing methods, comparatively processes the collected experimental data, and provides guidelines for heterogeneous structures testing.

Establishment of a Flow-Through System for the Macrophyte Growth Inhibition Test (OECD 239) Including Photosynthetic Activity Measurement to Determine Early Effects.

Maintaining constant exposure concentrations during ecotoxicological studies while testing rapidly degradable substances is a challenge. To achieve stable concentrations during exposure, flow-through systems are used. To assess the impact of substances on higher aquatic plants, the 14-day macrophyte water-sediment Myriophyllum spicatum growth inhibition test (Organisation for Economic Co-operation and Development [OECD, 2014a] test guideline 239) only includes a static or a semistatic test design. The main aim of our study was to investigate the applicability of a flow-through system for M. spicatum. The standard OECD test design was miniaturized, and a flow-through system with spill-over was developed to achieve stable exposure concentrations of a rapidly degrading substance. The main endpoints were total shoot length and fresh and dry weight. Photosynthetic activity was used as an endpoint for the identification of early effects using the noninvasive Image-Producing Pulse Amplitude Modulation (IMAGING-PAM) procedure. Atorvastatin (AV; fast degrading) and bentazone (BT; photosynthesis inhibitor) were used as model substances to observe differences of the effect concentration depending on the test design. At higher exposure levels of AV, stronger necrosis combined with lower effect concentrations was observed in the flow-through test compared with the semistatic test, indicating the applicability of the flow-through test for evaluating degradable substances. The test with BT demonstrated a concentration-dependent decrease in the photosynthetic yield (Y(II)) from day 3 onward even before macroscopically visible changes occurred. Our results show that the flow-through system in the macrophyte growth inhibition test (OECD test guideline 239; 2014a) is a suitable alternative when one is testing rapidly degradable substances such as AV. In addition, we showed that photosynthetic yield can serve as a supplementary endpoint, when one is testing substances with photosynthesis inhibition as a mode of action. Environ Toxicol Chem 2024;00:1-12. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Characterization of the in vitro penetration and first-pass metabolism of genistein and daidzein using human and pig skin explants and Phenion full-thickness skin models.

OECD test guideline compliant skin penetration studies, which also comply with the SCCS basic criteria, are lacking for genistein and daidzein. Therefore, we have measured their penetration and metabolism using ex vivo explants of fresh (i.e., metabolically viable) pig skin, fresh and frozen human skin, and Phenion full-thickness (FT) models. Preliminary studies using fresh pig skin helped to define the optimal experimental conditions. The dermal absorption of 10nmoles/cm2 genistein and daidzein in ethanol was comparable in all four models. A first-pass metabolism in skin to glucuronide and sulfate metabolites was demonstrated for both chemicals in all models except frozen human skin. The main difference between fresh skin models was the overall extent of metabolism and the relative ratio of each metabolite, for example, much lower sulfate conjugates were formed in pig skin incubations. The extent of parent chemical metabolized and the contribution of the glucuronide pathway were relatively lower in PhenionFT models than in fresh human skin, possibly due to a higher penetration rate in this model and differences in the expression of functional metabolizing enzymes. When metabolism in human skin was abolished by freezing, more radiolabelled chemical remained in the skin tissue but the overall dermal absorption was unchanged. In conclusion, this initial characterization study showed that all models tested indicated that genistein and daidzein extensively penetrated the skin when applied to skin in ethanol. All fresh skin models produced the same metabolites, with the known species difference in the sulfation pathway demonstrated in pig skin.

Human relevance of in vivo and in vitro skin irritation tests for hazard classification of pesticides

Background: Test methods to inform hazard characterization and labeling of pesticides to protect human health are typically conducted using laboratory animals, and for skin irritation/corrosion the rabbit Draize test is currently required by many regulatory agencies. Although the Draize test is generally regarded to provide protective classifications for human health, new approach methodologies (NAMs) have been developed that offer more human relevant models that circumvent the uncertainty associated with species differences that exist between rabbits and humans. Despite wide applicability and use of these test methods across a broad range of chemicals, they have not been widely adopted for testing pesticides and pesticidal formulations. One of the barriers to adoption of these methods in this sector is low concordance with results from the Draize rabbit test, particularly for chemicals within the mild to moderate irritation spectrum. Methods: This review compares and contrasts the extent to which available models used in skin irritation testing mimic the anatomy and physiology of human skin, and how each aligns with the known key events leading to chemically-induced adverse skin irritation and corrosion. Doing so fully characterizes the human relevance of each method. Results: As alternatives to the rabbit Draize test, several protocols using ex vivo, in chemico, and in vitro skin models are available as internationally harmonized test guidelines. These methods rely on a variety of models of human skin, including excised rodent skin, synthetic biochemical models of barrier function, cell culture systems, and reconstructed human tissue models. We find these models exhibit biological and mechanistic relevance aligned with human skin irritation responses. Further, recent retrospective analyses have shown that the reproducibility of the Draize test is less than 50% for mild and moderate responses, with many of the replicate predictions spanning more than one category (e.g., a moderate response reported in one study followed by a non-irritant response reported in another study). Conclusions: Based on this comparative evaluation, we recommend top-down and bottom-up testing strategies that use the most human relevant in vitro test methods for skin irritation and corrosion classification of pesticides and pesticide formulations. To further discriminate among mild and non-irritant formulations, optimization of a cytokine release protocol and subsequent analyses of reference formulation test results is recommended.

Limitations and Modifications of Skin Sensitization NAMs for Testing Inorganic Nanomaterials.

Since 2020, the REACh regulation requires toxicological data on nanoforms of materials, including the assessment of their skin-sensitizing properties. Small molecules' skin sensitization potential can be assessed by new approach methodologies (NAMs) addressing three key events (KE: protein interaction, activation of dendritic cells, and activation of keratinocytes) combined in a defined approach (DA) described in the OECD guideline 497. In the present study, the applicability of three NAMs (DPRA, LuSens, and h-CLAT) to nine materials (eight inorganic nanomaterials (NM) consisting of CeO2, BaSO4, TiO2 or SiO2, and quartz) was evaluated. The NAMs were technically applicable to NM using a specific sample preparation (NANOGENOTOX dispersion protocol) and method modifications to reduce interaction of NM with the photometric and flowcytometric read-outs. The results of the three assays were combined according to the defined approach described in the OECD guideline No. 497; two of the inorganic NM were identified as skin sensitizers. However, data from animal studies (for ZnO, also human data) indicate no skin sensitization potential. The remaining seven test substances were assessed as "inconclusive" because all inorganic NM were outside the domain of the DPRA, and the achievable test concentrations were not sufficiently high according to the current test guidelines of all three NAMs. The use of these NAMs for (inorganic) NM and the relevance of the results in general are challenged in three ways: (i) NAMs need modification to be applicable to insoluble, inorganic matter; (ii) current test guidelines lack adequate concentration metrics and top concentrations achievable for NM; and (iii) NM may not cause skin sensitization by the same molecular and cellular key events as small organic molecules do; in fact, T-cell-mediated hypersensitivity may not be the most relevant reaction of the immune system to NM. We conclude that the NAMs adopted by OECD test guidelines are currently not a good fit for testing inorganic NM.

Optimal cut-offs of vibration-controlled transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis.

Opinions differ regarding vibration-controlled transient elastography and magnetic resonance elastography (VCTE/MRE) cut-offs for diagnosing advanced fibrosis (AF) in patients with non-alcoholic fatty liver disease (NAFLD). We investigated the diagnostic performance and optimal cut-off values of VCTE and MRE for diagnosing AF. Literature databases, including Medline, EMBASE, Cochrane Library, and KoreaMed, were used to identify relevant studies published up to June 13, 2023. We selected studies evaluating VCTE and MRE regarding the degree of liver fibrosis using liver biopsy as the reference. The sensitivity, specificity, and area under receiver operating characteristics curves (AUCs) of the pooled data for VCTE and MRE for each fibrosis stage and optimal cut-offs for AF were investigated. A total of 19,199 patients from 63 studies using VCTE showed diagnostic AUC of 0.83 (95% confidence interval: 0.80-0.86), 0.83 (0.80-0.86), 0.87 (0.84-0.90), and 0.94 (0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. Similarly, 1,484 patients from 14 studies using MRE showed diagnostic AUC of 0.89 (0.86-0.92), 0.92 (0.89-0.94), 0.89 (0.86-0.92), and 0.94 (0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. The diagnostic AUC for AF using VCTE was highest at 0.90 with a cut-off of 7.1-7.9 kPa, and that of MRE was highest at 0.94 with a cut-off of 3.62-3.8 kPa. VCTE (7.1-7.9 kPa) and MRE (3.62-3.8 kPa) with the suggested cut-offs showed favorable accuracy for diagnosing AF in patients with NAFLD. This result will serve as a basis for clinical guidelines for non-invasive tests and differential diagnosis of AF.

Petrography and geomechanical properties of some mine waste rocks from the Tarkwaian Group in Ghana: implications for their use as aggregates in general engineering works

This research investigated some mine waste rocks from the southwestern part of the Tarkwaian Group in Ghana to check their suitability for general engineering works using petrography and geomechanical characteristics of the rocks. The rocks were subjected to a total of ten (10) tests, including Aggregate impact value (AIV), Aggregate crushing value (ACV), Loss Angeles abrasion (LAA), Specific gravity (SG), and Water absorption (WA), as well as flakiness and elongation index, slake durability (SD), chloride test (CT), sulphate test (ST), and ten percent fines (TPF). The tests were carried out per the American Society for Testing and Materials guidelines (ASTM). The following average test results were obtained: AIV (7.12%), ACV (15.60%), LAA (23.16%), TPF (269.7 kN), sulphate (0.0215%), chloride (0.00123%), flakiness (39.5%) and elongation (39.4%). The mine waste rocks are dominated by quartz and sericite, according to the petrographic examination and thus, can be classified as quartzites. Except for the flakiness and elongation index tests, all the results were consistent with the ASTM standards. The analysis carried out on the selected mine waste rocks from the southwestern part of the Tarkwaian Group could be catastrophic for heavy engineering works such as roads, bridges, and heavy buildings but can be used for pavements, lightweight buildings, monuments, and decoratives due to the percentage of quartz present to compensate for the weakness posed by the sericite.

KASL clinical practice guidelines for noninvasive tests to assess liver fibrosis in chronic liver disease.

KASL clinical practice guidelines for noninvasive tests to assess liver fibrosis in chronic liver disease.

Diagnostic and clinical utility of comprehensive multigene panel testing for patients with neuropathy.

Prior to next-generation sequencing (NGS), the evaluation of a patient with neuropathy typically consisted of screening for acquired causes, followed by clinical genetic testing of PMP22, MFN2, GJB1, and MPZ in patients with a positive family history and symptom onset prior to age 50. In this study, we examined the clinical utility of NGS in a large cohort of patients analyzed in a commercial laboratory. A cohort of 6849 adult patients underwent clinician-ordered peripheral neuropathy multigene panel testing ranging from 66 to 111 genes that included NGS and intragenic deletion/duplication analysis. A molecular diagnosis was identified for 8.4% of the cohort (n = 573/6849). Variants in PMP22, MFN2, GJB1, MPZ, and TTR accounted for 73.8% of molecular diagnoses. Results had potential clinical actionability for 398 (69.5%) patients. Our results suggest that 225/573 (39.3%) of molecular diagnoses and 113/398 (28.4%) of clinical interventions would have been missed if the testing approach had been restricted to older guidelines. Our results highlight the need for expanded genetic testing guidelines that account for the increased number of genes associated with hereditary neuropathy, address the overlap of acquired and hereditary neuropathy, and provide broader access to genetic diagnosis for patients.

Adaption of in vitro and in chemico phototoxicity tests for tattoo pigments and the effect of adsorption of the phototoxic contaminant benzo[a]pyrene to carbon black

Phototoxicity plays an important role in tattoo toxicology due to the skin's daily exposure to sunlight and the permanent deposition of pigments in skin. Here, we investigated in chemico reactive oxygen species generation using 2′,7′-dichlorodihydrofluorescein diacetate and in vitro phototoxicity towards skin fibroblasts based on the OECD Test Guideline 432.Proficiency substances, titanium dioxide (TiO2, anatase 30 nm, anatase 100 nm, rutile 30 nm), pigment red 22 (PR 22) with and without purification and carbon black (CB) were investigated. Phototoxic properties of benzo[a]pyrene (B[a]P) were investigated with and without adsorption to CB. Pigments were characterised by dynamic light scattering.All proficiency substances except for norfloxacin were predicted successfully and only TiO2 anatase exhibited phototoxicity in the cell-based approach. B[a]P showed the expected phototoxicity in contrast to B[a]P bound to carbon black. Upon UVA irradiation, only TiO2 pigment anatase and PR 22 generated ROS in the cell-free assay. DLS measurements showed a high degree of polydispersity/agglomeration.OECD Test Guideline 432 should be applied with an incubation time of 24 h when testing highly insoluble pigments. The in chemico ROS assay introduced below might serve as a quick screening test but may be further adapted to predict the in vitro outcome.

Screening persistent organic pollutants for effects on testosterone and estrogen synthesis at human-relevant concentrations using H295R cells in 96-well plates.

Many persistent organic pollutants (POPs) are suspected endocrine disruptors and it is important to investigate their effects at low concentrations relevant to human exposure. Here, the OECD test guideline #456 steroidogenesis assay was downscaled to a 96-well microplate format to screen 24 POPs for their effects on viability, and testosterone and estradiol synthesis using the human adrenocortical cell line H295R. The compounds (six polyfluoroalkyl substances, five organochlorine pesticides, ten polychlorinated biphenyls and three polybrominated diphenyl ethers) were tested at human-relevant levels (1 nM to 10 µM). Increased estradiol synthesis, above the OECD guideline threshold of 1.5-fold solvent control, was shown after exposure to 10 µM PCB-156 (153%) and PCB-180 (196%). Interestingly, the base hormone synthesis varied depending on the cell batch. An alternative data analysis using a linear mixed-effects model that include multiple independent experiments and considers batch-dependent variation was therefore applied. This approach revealed small but statistically significant effects on estradiol or testosterone synthesis for 17 compounds. Increased testosterone levels were demonstrated even at 1 nM for PCB-74 (18%), PCB-99 (29%), PCB-118 (16%), PCB-138 (19%), PCB-180 (22%), and PBDE-153 (21%). The MTT assay revealed significant effects on cell viability after exposure to 1 nM of perfluoroundecanoic acid (12%), 3 nM PBDE-153 (9%), and 10 µM of PCB-156 (6%). This shows that some POPs can interfere with endocrine signaling at concentrations found in human blood, highlighting the need for further investigation into the toxicological mechanisms of POPs and their mixtures at low concentrations relevant to human exposure.

Acute and subacute oral toxicity evaluation of Ayurvedic formulation Tapyadi loha in rats

Ayurveda is one of the oldest systems of traditional medicine that provides treatments for a wide range of acute and chronic health problems. It is a common myth amongst people that Ayurvedic drugs have no side effects, whereas the fact is that these drugs can cause adverse effects. Despite their wide use, the safety data of many Ayurvedic formulations are still unavailable. Tapyadi loha is an Ayurvedic formulation traditionally claimed for iron deficiency anemia in pregnant and non-pregnant patients. However, no scientific study has been conducted to evaluate its oral toxicity. Hence, the present study evaluated the acute and subacute oral toxicity of the Tapyadi loha according to the OECD test guidelines 425 and 407, respectively. Tapyadi loha did not cause mortality nor any signs of toxicity when given once orally at a dose of 2000 mg/kg. Subacute toxicity study showed no mortality as well as no behavioral, hematological, biochemical and histopathological abnormalities in rats treated with Tapyadi loha formulation at 250, 500 and 1000 mg/kg for 28 days. It is concluded that the Tapyadi loha is safe at a single dose of 2000 mg/kg and 28 days repeated dose of 1000 mg/kg by oral route in rats.

Inhalation Toxicity Screening of Consumer Products Chemicals using OECD Test Guideline Data-based Machine Learning Models

This study aimed to screen the inhalation toxicity of chemicals found in consumer products such as air fresheners, fragrances, and anti-fogging agents submitted to K-REACH using machine learning models. We manually curated inhalation toxicity data based on OECD test guideline 403 (Acute inhalation), 412 (Sub-acute inhalation), and 413 (Sub-chronic inhalation) for 1709 chemicals from the OECD eChemPortal database. Machine learning models were trained using ten algorithms, along with four molecular fingerprints (MACCS, Morgan, Topo, RDKit) and molecular descriptors, achieving F1 scores ranging from 51 % to 91 % in test dataset. Leveraging the high-performing models, we conducted a virtual screening of chemicals, initially applying them to data-rich chemicals generally used in occupational settings to determine the prediction uncertainty. Results showed high sensitivity (75 %) but low specificity (23 %), suggesting that our models can contribute to conservative screening of chemicals. Subsequently, we applied the models to consumer product chemicals, identifying 79 as of high concern. Most of the prioritized chemicals lacked GHS classifications related to inhalation toxicity, even though they were predicted to be used in many consumer products. This study highlights a potential regulatory blind spot concerning the inhalation risk of consumer product chemicals while also indicating the potential of artificial intelligence (AI) models to aid in prioritizing chemicals at the screening level.

The Chinese version of patient experience with treatment and self-management (PETS vs. 2.0): translation and validation in patients with multimorbidity in primary care in Hong Kong

BackgroundValidated and comprehensive tools to measure treatment burden are needed for healthcare professionals to understand the treatment burden of patients in China. The study aimed to translate and validate the Chinese version of Patient Experience with Treatment and Self-management (PETS vs. 2.0) in patients with multimorbidity in primary care.MethodologyThe translation process of the 60-item PETS vs. 2.0 followed the Functional Assessment of Chronic Illness Therapy (FACIT) Translation, Formatting, and Testing Guidelines. Computer-assisted assessments were conducted in adult primary care patients with multimorbidity from three general out-patient clinics in Hong Kong. A sample of 502 patients completed the assessments from July to December 2023. Internal reliability was examined using Cronbach’s alphas for each domain of the PETS vs. 2.0. Concurrent validity was assessed through the correlations between different domains of PETS vs. 2.0 with established measures including quality of life, frailty, and depression. Confirmatory Factor Analysis (CFA) with maximum likelihood method was carried out to assess the construct validity.ResultsThe mean age of participants was 64.9 years old and 56.2% were female. Internal consistency reliability was acceptable (alpha ≥ 0.70) for most domains. Higher scores of PETS domains were significantly correlated with worse quality of life, higher level of frailty, and more depressive symptoms (p < 0.05). In CFA, after setting the covariances on the error variances, the adjusted model revealed an acceptable model fit (χ2/df = 1.741; root mean square error of approximation (RMSEA) = 0.038; standardized root mean square residual (SRMR) = 0.058; comparative fit index (CFI) = 0.911; Tucker-Lewis Index (TLI) = 0.903). All standardized factor loadings were 0.30 or above. Significant positive correlations between the latent factors were found for all factor pairs (correlation coefficient < 0.8).ConclusionsThe Chinese version of PETS vs. 2.0 is a reliable and valid tool for assessing the perceived treatment burden in patients with multimorbidity in primary care. All domains and items in the original questionnaires were retained.

Adherence to national Lynch syndrome testing guidelines for colorectal cancer in an Aotearoa New Zealand hospital-based population.

Lynch syndrome (LS) is estimated to affect 1-3.9% of patients with colorectal cancer (CRC). Testing for LS is important in determining management and establishing surveillance for "Lynch families". Previous studies have identified poor rates of testing for LS in CRC patients. This study aimed to describe adherence to guidelines for testing of newly diagnosed CRC for LS. A single institution cohort study of patients over 18 years with colorectal adenocarcinoma from 2018-2022 in Te Tai Tokerau, Aotearoa New Zealand was conducted. Rates of baseline immunohistochemistry (IHC) testing for mismatch repair (MMR) deficiency, further testing for MLH1-deficient cases and rates of germline mutational analysis were audited to determine adherence to national guidelines. The rate of LS in newly diagnosed CRC was estimated. Six hundred and sixty patients were eligible for universal testing for LS, of which 84% (n=553) completed initial IHC testing. MMR deficiency was reported in 20% (n=114) cases. Eighty-nine percent (n=101) was attributable to MLH1 deficiency, of which 99% (n=100) were appropriately tested for BRAF-V600E mutation. Sixty-four percent (4/11) patients indicated for hypermethylation testing were appropriately tested. Seventeen patients had an indication for germline mutational analysis, of which only 29% (n=5) were tested. The estimated incidence of LS in newly diagnosed CRC was 0.7-3.8%. Compliance with initial IHC testing was good. However, there is a need to improve rates of confirmation genetic testing. The incidence of confirmed LS in this study is 0.7%, however this may be as high as 3.9%.

A conditional reasoning test for risk and incident propensity: Development and validation.

The present study outlines the development and initial validation of a conditional reasoning test for risk and incident propensity (CRT-RIP). Individuals carry with them a wide array of experiences, attitudes, and dispositions that may influence their proneness for risk-taking and incident involvement. Yet, measuring risk propensity has proven challenging due to the high levels of transparency found in the self-report measures that are presently available. We initially developed 28 conditional reasoning items to measure risk and incident propensity. With four developmental samples, we evaluated item characteristics. After applying item decision guidelines for conditional reasoning tests, we retained 14 items. Using three test samples and with the 14-item CRT-RIP, we assessed predictive and incremental validity over five-factor personality traits and an explicit, self-report measure of risk propensity. With one final sample, we provided further validation of the 14-item CRT-RIP. Findings demonstrate initial success in predicting various safety behaviors and outcomes. Ability to measure risk propensity and to predict safety behaviors is valuable because of the profound consequences that may proceed failure to enact safety behaviors including property damage, injury, illness, or even death. We discuss potential applications and suggest directions for future research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Brazilian Guideline for Exercise Testing in Children and Adolescents - 2024.

Classes de Recomendação Classe I: Condições para as quais há evidências conclusivas e, na sua falta, consenso geral de que o procedimento é seguro e útil/eficaz. Classe II: Condições para as quais há evidências conflitantes e/ou divergência de opinião sobre a segurança e utilidade/eficácia do procedimento. Classe IIa: Peso ou evidência/opinião a favor do procedimento. A maioria aprova. Classe IIb: Segurança e utilidade/eficácia menos estabelecidas, havendo opiniões divergentes. Classe III: Condições para as quais há evidências e/ou consenso de que o procedimento não é útil/eficaz e, em alguns casos, pode ser prejudicial. Níveis de Evidência Nível A: Dados obtidos a partir de múltiplos estudos randomizados de bom porte, concordantes e/ou de metanálise robusta de estudos randomizados. Nível B: Dados obtidos a partir de metanálise menos robusta, a partir de um único estudo randomizado e/ou de estudos observacionais. Nível C: Dados obtidos de opiniões consensuais de especialistas.