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Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals in whom it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologues. Using RNA sequencing, we show how 5 splice-site use is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 base pair region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide.

The contrast between the disruption of genome topology after cohesin loss and the lack of downstream gene expression changes instigates intense debates regarding the structure-function relationship between genome and gene regulation. Here, by analyzing transcriptome and chromatin accessibility at the single-cell level, we discover that, instead of dictating population-wide gene expression levels, cohesin supplies a general function to neutralize stochastic coexpression tendencies of cis-linked genes in single cells. Notably, cohesin loss induces widespread gene coactivation and chromatin co-opening tens of million bases apart in cis. Spatial genome and protein imaging reveals that cohesin prevents gene co-bursting along the chromosome and blocks spatial mixing of transcriptional hubs. Single-molecule imaging shows that cohesin confines the exploration of diverse enhancer and core promoter binding transcriptional regulators. Together, these results support that cohesin arranges nuclear topology to control gene coexpression in single cells.

Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and, with new innovative methods, can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing collected at the Broad Institute Center for Mendelian Genomics of the Genomics Research to Elucidate the Genetics of Rare Diseases consortium and analyzed using the seqr platform. The addition of CNV detection to exome analysis identified causal CNVs for 171 families (2.6%). The estimated sizes of CNVs ranged from 293 bp to 80 Mb. The causal CNVs consisted of 140 deletions, 15 duplications, 3 suspected complex structural variants (SVs), 3 insertions, and 10 complex SVs, the latter two groups being identified by orthogonal confirmation methods. To classify CNV variant pathogenicity, we used the 2020 American College of Medical Genetics and Genomics/ClinGen CNV interpretation standards and developed additional criteria to evaluate allelic and functional data as well as variants on the X chromosome to further advance the framework. We interpreted 151 CNVs as likely pathogenic/pathogenic and 20 CNVs as high-interest variants of uncertain significance. Calling CNVs from existing exome data increases the diagnostic yield for individuals undiagnosed after standard testing approaches, providing a higher-resolution alternative to arrays at a fraction of the cost of genome sequencing. Our improvements to the classification approach advances the systematic framework to assess the pathogenicity of CNVs.

ImportanceMagnetic resonance imaging (MRI) surveillance is offered to women with a pathogenic variant in the BRCA1 or BRCA2 gene who face a high lifetime risk of breast cancer. Surveillance with MRI is effective in downstaging breast cancers, but the association of MRI surveillance with mortality risk has not been well defined.ObjectiveTo compare breast cancer mortality rates in women with a BRCA1 or BRCA2 sequence variation who entered an MRI surveillance program with those who did not.Design, setting, and participantsWomen with a BRCA1 or BRCA2 sequence variation were identified from 59 participating centers in 11 countries. Participants completed a baseline questionnaire between 1995 and 2015 and a follow-up questionnaire every 2 years to document screening histories, incident cancers, and vital status. Women who had breast cancer, a screening MRI examination, or bilateral mastectomy prior to enrollment were excluded. Participants were followed up from age 30 years (or the date of the baseline questionnaire, whichever was later) until age 75 years, the last follow-up, or death from breast cancer. Data were analyzed from January 1 to July 31, 2023.ExposuresEntrance into an MRI surveillance program.Main outcomes and measuresCox proportional hazards modeling was used to estimate the hazard ratios (HRs) and 95% CIs for breast cancer mortality associated with MRI surveillance compared with no MRI surveillance using a time-dependent analysis.ResultsA total of 2488 women (mean [range] age at study entry 41.2 [30-69] years), with a sequence variation in the BRCA1 (n = 2004) or BRCA2 (n = 484) genes were included in the analysis. Of these participants, 1756 (70.6%) had at least 1 screening MRI examination and 732 women (29.4%) did not. After a mean follow-up of 9.2 years, 344 women (13.8%) developed breast cancer and 35 women (1.4%) died of breast cancer. The age-adjusted HRs for breast cancer mortality associated with entering an MRI surveillance program were 0.20 (95% CI, 0.10-0.43; P

ImportancePreventive bilateral salpingo-oophorectomy is offered to women at high risk of ovarian cancer who carry a pathogenic variant in BRCA1 or BRCA2; however, the association of oophorectomy with all-cause mortality has not been clearly defined.ObjectiveTo evaluate the association between bilateral oophorectomy and all-cause mortality among women with a BRCA1 or BRCA2 sequence variation.Design, setting, and participantsIn this international, longitudinal cohort study of women with BRCA sequence variations, information on bilateral oophorectomy was obtained via biennial questionnaire. Participants were women with a BRCA1 or BRCA2 sequence variation, no prior history of cancer, and at least 1 follow-up questionnaire completed. Women were followed up from age 35 to 75 years for incident cancers and deaths. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs for all-cause mortality associated with a bilateral oophorectomy (time dependent). Data analysis was performed from January 1 to June 1, 2023.ExposuresSelf-reported bilateral oophorectomy (with or without salpingectomy).Main outcomes and measuresAll-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.ResultsThere were 4332 women (mean age, 42.6 years) enrolled in the cohort, of whom 2932 (67.8%) chose to undergo a preventive oophorectomy at a mean (range) age of 45.4 (23.0-77.0) years. After a mean follow-up of 9.0 years, 851 women had developed cancer and 228 had died; 57 died of ovarian or fallopian tube cancer, 58 died of breast cancer, 16 died of peritoneal cancer, and 97 died of other causes. The age-adjusted HR for all-cause mortality associated with oophorectomy was 0.32 (95% CI, 0.24-0.42; P

Abstract Background Concentrations of plasma per and poly-fluoroalkyl substances (PFAS) are elevated in the Inuit population of Nunavik and may be causing adverse health effects. Respiratory health outcomes have been associated with PFAS, but have not been explored in Inuit communities. The aim of the study was to examine the association between PFAS and respiratory health outcomes, and the moderating role of nutritional biomarkers. Methods We included up to 1298 participants of the Qanuilirpitaa? 2017 survey aged 16–80 years. Generalized regression models were used to estimate the associations between six individual PFAS congeners and four self-reported symptoms, four spirometry measures, and physician-diagnosed asthma. Outcomes associated with PFAS from single chemical models were further explored using Bayesian Kernel Machine Regression (BKMR). The modifying effect of n-3 PUFA in red blood cell quartiles and vitamin D deficiency were examined on the associations between PFAS and respiratory outcomes. Results PFNA and PFOS were associated with asthma (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.12, 2.32; OR 1.45 95% CI 1.04, 2.03). PFOA, PFNA, PFDA and PFHxS were associated with a decrease in the ratio between the forced expiratory volume in the first second and forced vital capacity (FEV1/FVC). No associations were observed with self-reported respiratory symptoms. No associations were observed between a PFAS mixture and asthma. Some associations were modified by nutritional factors, namely, stronger associations between PFOA and PFHxS and asthma with lower n-3 PUFA levels and stronger associations between PFDA, PFUnDA and PFOS and FEV1/FVC with vitamin D deficiency. Conclusion These findings add to the growing literature on the impacts of PFAS on respiratory health, and the importance of their global regulation. Associations were modified by nutritional factors pointing to the nutritional value of traditional Inuit foods.

Abstract The World Health Organization has designated Pseudomonas aeruginosa as a critical pathogen for the development of new antimicrobials. Bacterial viruses, or bacteriophages, have been used in various clinical settings, commonly called phage therapy, to address this growing public health crisis. Here, we describe a high-resolution structural atlas of a therapeutic, contractile-tailed Pseudomonas phage, Pa193. We used bioinformatics, proteomics, and cryogenic electron microscopy single particle analysis to identify, annotate, and build atomic models for 21 distinct structural polypeptide chains forming the icosahedral capsid, neck, contractile tail, and baseplate. We identified a putative scaffolding protein stabilizing the interior of the capsid 5-fold vertex. We also visualized a large portion of Pa193 ~ 500 Å long tail fibers and resolved the interface between the baseplate and tail fibers. The work presented here provides a framework to support a better understanding of phages as biomedicines for phage therapy and inform engineering opportunities.

The aim of this study was to describe the environmental adaptations made by early childhood centre (ECC) educators to support the literacy skills of the children in their group through daily activities, following professional development (training and coaching). Data were collected using questionnaires administered before and after the experiment, as well as a logbook completed by the four participating educators. Qualitative analysis reveals that, as a result of professional development, the variety and quantity of environmental adaptations proposed by the educators increased, particularly in terms of environmental writing, printouts, and literacy materials made available. In conclusion, the enrichment of the physical environment in literacy would allow, among other things, the children to access the material themselves, which would promote their interest and their involvement in early literacy activities. Keywords: early literacy, physical environment, childcare centre, professional development Cette etude visait a decrire les adaptations de l'environnement realisees par le personnel educateur d'un centre de la petite enfance (CPE) pour soutenir les habiletes en litteratie des enfants de leur groupe lors des activites quotidiennes, et ce, a la suite d'un developpement professionnel (formation et accompagnement). Le remplissage d'un questionnaire avant et apres la demarche de developpement professionnel ainsi que la tenue d'un journal de bord par les quatre educatrices participantes ont permis de recueillir les donnees analysees. L'analyse qualitative revele qu'a la suite du developpement professionnel, la variete et la quantite des adaptations de l'environnement proposees par les educatrices ont augmente, notamment sur le plan des ecrits imprimes environnementaux ainsi que du materiel en litteratie mis a la disposition des enfants. En conclusion, l'enrichissement de l'environnement physique en litteratie permettrait entre autres aux enfants d'acceder eux-memes au materiel, ce qui favoriserait leur interet et leur implication pour les activites d'eveil a la lecture et a l'ecriture. Mots-cles: litteratie emergente, environnement physique, milieu de garde, developpement professionnel, Introduction L'importance de favoriser le developpement des habiletes emergentes en litteratie (eveil a la lecture et a l'ecriture) chez les jeunes enfants est reconnue depuis plusieurs annees (Girolametto et al., [...]

Abstract People who inject drugs (PWID) are often members of HIV/AIDS risk networks, where individuals engage in sexual and injection risk behavior. Engagement in HIV care is important for this population. Low socioeconomic status, stigmatization, and lack of access to medical care often complicate successful engagement in the HIV cascade of care for PWID. This study investigates how individual's attitudes about how much control they have over HIV/AIDS risk in their life (i.e., locus of control and self-blame) affect health-seeking behavior in PWID participants and their community members. We applied causal inference methodology to PWID HIV risk networks ascertained from the Social Factors and HIV Risk Study (SFHR) conducted between 1991 and 1993 in Bushwick, Brooklyn, New York. We estimated protective disseminated effects of attitudes toward HIV/AIDS on the health-seeking behaviors of others in the PWID community. In other words, a positive attitude toward controlling HIV/AIDS can improve the health-seeking behavior of other members of the community who report a pessimistic attitude toward HIV/AIDS control. Given this finding, we also discuss potential network interventions to improve health-seeking behavior among both PWID individuals who receive the intervention and others in the PWID network informed by our analysis of disseminated effects.

Abstract Background The aim of this study is to explore the effect of treadmill slope on ground reaction forces and local muscle oxygenation as putative limiting factors of peak oxygen uptake in graded maximal incremental running tests. Thirteen trained male runners completed five maximal incremental running tests on treadmill at − 15%, − 7.5%, 0%, 7.5% and 15% slopes while cardiorespiratory and local muscle oxygenation responses as well as ground reaction forces were continuously recorded. Blood lactate concentration and isometric knee extensor torque were measured before and after each test. Results Peak oxygen uptake was lower at − 15% slope compared to all other conditions (from − 10 to − 17% lower, p

The global use of pesticides is increasing; however, few studies have examined the exposure of current-use pesticide exposure in Inuit populations. Some current use pesticides are also capable of long-range transport, potentially increasing exposures to northern populations. The study aim was to analyse pesticide (chlorophenoxy, organophosphates, and pyrethroid pesticide) biomarker levels in pooled samples from an Inuit population in Nunavik, Quebec. Thirty pooled samples from the Qanuilirpitaa? 2017 survey (Q2017) from individuals aged 16–80 years were included. Creatinine-adjusted arithmetic (AM) were compared by sex, age, and region sub-groups, and geometric mean concentrations (GM) were compared to those in the Canadian Health Measures Survey (CHMS). Most analysed pesticide biomarkers were detected, and PNP (a metabolite of methyl and ethyl parathion), trans-DCCA (a metabolite of pyrethroids), and 3,5,6-TCP (a metabolite of chlorpyrifos) had the highest concentrations. Concentrations in Q2017 were largely similar to or less than CHMS concentrations. Although not significant, there was a general increase in 2,4-D (a chlorophenoxy biomarker), 3,5,6-TCP, 3-PBA (a metabolite of pyrethroids), and trans-DCCA with increasing age. Concentrations were also somewhat higher in females versus males, but these were not significant. Environmental exposures to current use pesticides were detected in Nunavik and concentrations were similar to or less than those in the general Canadian population. Regular monitoring of current use pesticide exposures is recommended given the increasing global use of pesticides.

The Arctic Monitoring Assessment Program (AMAP) is tasked with monitoring and assessing the status of environmental contaminants in the Arctic, documenting levels and trends, and producing science-based assessments. The objectives of this paper are to present the current levels of persistent organic pollutants (POPs) across the Arctic, and to identify trends and knowledge gaps as detailed in the most recent AMAP Human Health Assessment Report. Many Arctic populations continue to have elevated levels of these contaminants, and the highest levels of POPs were observed in populations from Greenland, Faroe Islands, and Nunavik (Canada), as well as populations in the coastal Chukotka district (Russia) for legacy POPs only. Concentrations of most POPs are declining in Arctic populations in regions where time trends data exist, although the declines are not consistent across all regions. The exceptions are per- and polyfluoroalkyl substances, with concentrations of some long-chain PFAS such as perfluorononanoic acid increasing in populations in Nunavik, Greenland and Sweden. This paper provides a more extensive summary of levels of contaminants in adults, pregnant women, and children across the Arctic than previous AMAP human health assessments, particularly for levels of long-chain PFAS, which are currently under consideration for inclusion in the Stockholm Convention.

The 2021 Arctic Monitoring Assessment Program (AMAP)’s Human Health Assessment report presents a summary of the presence of contaminants in human populations across the circumpolar Arctic and provides an update to the previous assessment released in 2015. The primary objective of this paper is to summarise some of these findings by describing the current levels of metals across the Arctic, including key regional and temporal trends based on available national data and literature, and highlight knowledge gaps. Many Arctic populations continue to have elevated levels of these contaminants, and the highest levels of mercury (Hg) were observed in populations from Greenland, Faroe Islands, and Nunavik (Canada). Still, concentrations of several metals are declining in Arctic populations in regions where time trends data exist, although the declines are not consistent across all regions. The 2021 AMAP human health assessment report and this paper provide an extensive summary of levels of metals and trace elements in adults, pregnant women, and children across the Arctic.

Arctic populations are amongst the highest exposed populations to long-range transported contaminants globally, with the main exposure pathway being through the diet. Dietary advice is an important immediate means to address potential exposure and help minimize adverse health effects. The objective of this work is to enable easier access to dietary advice and communication guidance on contaminants with a focus on the Arctic. This manuscript is part of a special issue summarizing the Arctic Monitoring and Assessment Programme’s Assessment 2021: Human Health in the Arctic. The information was derived with internet searches, and by contacting relevant experts directly. Results include risk communication efforts in European Arctic countries, effectiveness evaluation studies for several Arctic countries, experience of social media use, and the advantages and challenges of using social media in risk communication. We found that current risk communication activities in most Arctic countries emphasize the importance of a nutritious diet. Contaminant-related restrictions are mostly based on mercury; a limited amount of dietary advice is based on other contaminants. While more information on effectiveness evaluation was available, specific information, particularly from Arctic countries other than Canada, is still very limited.

Abstract Background Scholars recommend providing migrants living with HIV (MLWH) with free treatment, rapidly, once linked to care to optimize their HIV-related experiences and health outcomes. Quantitative evaluations of patient-reported measures for MLWH in such models are necessary to explore the viability of these recommendations. Methods Within a 96-week prospective cohort study at a multidisciplinary HIV clinic, participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for free and rapidly following care linkage. Eight patient-reported measures were administered at weeks 4, 24, and 48: (1) mMOS-SS to measure perceived social support; (2) IA-RSS to measure internalized stigma; (3) K6 to measure psychological distress; (4) PROMIS to measure self-efficacy with treatment taking; (5) G-MISS to measure perceived compliance with clinicians’ treatment plans; (6) HIVTSQ to measure treatment satisfaction; (7) CARE to measure perceived provider empathy; and (8) PRPCC to measure perceived clinician cultural competence. Linear mixed modelling with bootstrapping was conducted to identify significant differences by sociodemographics and time. Results Across weeks 4, 24, and 48, results suggest that MLWH enrolled in this study experienced moderate levels of social support; elevated levels of HIV-related stigma; moderate levels of distress; high self-efficacy with daily medication self-management; great compliance with clinicians’ treatment plans; high treatment satisfaction; high perceived empathy; and high perceived cultural competence. Experience of social support (i.e., mMOS-SS scores) differed significantly by birth region. Experience of HIV-related stigma (i.e., IA-RSS scores) differed significantly by birth region, age, and language. Experience of distress (i.e., K6 scores) differed significantly by sexual orientation. Experience of treatment satisfaction (i.e., HIVTSQ scores) differed significantly by birth region and age. No significant differences were identified by time for any measure. Conclusion Overall, participants expressed positive experiences around treatment and care, alongside comparably lower perceptions of social support, internalized stigma, and distress, potentially underscoring a need to embed targeted, well-funded, and accessible mental health support within HIV care models.

Abstract Background An intense and precocious interest in written material, together with a discrepancy between decoding and reading comprehension skills are defining criteria for hyperlexia, which is found in up to 20% of autistic individuals. It may represent the extreme end of a broader interest in written material in autism. This study examines the magnitude and nature of the interest in written material in a large population of autistic and non-autistic children. Methods All 701 children (391 autistic, 310 non-autistic) under the age of 7 referred to an autism assessment clinic over a span of 4 years were included. Ordinal logistic regressions assessed the association between diagnosis and the level of interest in letters and numbers. A nested sample of parents of 138 autistic, 99 non-autistic clinical, and 76 typically developing (TD) children completed a detailed questionnaire. Cox proportional hazards models analyzed the age of emergence of these interests. Linear regressions evaluated the association between diagnosis and interest level. The frequency of each behaviour showing interest and competence with letters and numbers were compared. Results In the two studies, 22 to 37% of autistic children had an intense or exclusive interest in letters. The odds of having a greater interest in letters was 2.78 times higher for autistic children than for non-autistic clinical children of the same age, and 3.49 times higher for the interest in numbers, even if 76% of autistic children were minimally or non-verbal. The age of emergence of these interests did not differ between autistic and TD children and did not depend on their level of oral language. Non-autistic children showed more interest in letters within a social context. Limitations The study holds limitations inherent to the use of a phone questionnaire with caregivers and missing sociodemographic information. Conclusions The emergence of the interest of autistic children toward written language is contemporaneous to the moment in their development where they display a strong deficit in oral language. Together with recent demonstrations of non-social development of oral language in some autistic children, precocious and intense interest in written material suggests that language acquisition in autism may follow an alternative developmental pathway.

Arctic char (Salvelinus alpinus) is a salmonid fish that is the second-most consumed country food species by Nunavimmiut. Its nutritional quality is determined by omega-3 fatty acids and carotenoid pigments. Those molecules cannot be synthetized by fish and must be acquired through diet. We sampled Arctic char in 10 rivers from the three marine coastal regions of Nunavik (Hudson Bay, Hudson Strait, and Ungava Bay), described diet (stable isotopes δ13C and δ15N) and flesh quality (fatty acids and carotenoids, measured by chromatography) and assessed associations between both diet and flesh quality (including also bio-impedance and colorimetry). Our results suggested inter-regional differences in the diet and nutritional quality of Arctic char in Nunavik, where δ13C values indicated that the diet of Arctic char in Hudson Bay was more pelagic, while in Ungava Bay it was more coastal. We also observed inter-regional differences in omega-3 fatty acids and astaxanthin, the pigment responsible for the redness of the flesh color, where concentrations were highest in Ungava Bay Arctic char. In all sampling locations, Arctic char were an exceptional source of omega-3 fatty acids and astaxanthin, confirming its importance as a high-quality wild food. Our models suggest that astaxanthin, canthaxanthin, and water content influence flesh redness. Our data highlight inter-regional differences that could be taken in consideration to better predict the impact of climate change on fish quality and, ultimately, on Inuit diet and health.

Abstract Background A major obstacle faced by families with rare diseases is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years and causal variants are identified in under 50%, even when capturing variants genome-wide. To aid in the interpretation and prioritization of the vast number of variants detected, computational methods are proliferating. Knowing which tools are most effective remains unclear. To evaluate the performance of computational methods, and to encourage innovation in method development, we designed a Critical Assessment of Genome Interpretation (CAGI) community challenge to place variant prioritization models head-to-head in a real-life clinical diagnostic setting. Methods We utilized genome sequencing (GS) data from families sequenced in the Rare Genomes Project (RGP), a direct-to-participant research study on the utility of GS for rare disease diagnosis and gene discovery. Challenge predictors were provided with a dataset of variant calls and phenotype terms from 175 RGP individuals (65 families), including 35 solved training set families with causal variants specified, and 30 unlabeled test set families (14 solved, 16 unsolved). We tasked teams to identify causal variants in as many families as possible. Predictors submitted variant predictions with estimated probability of causal relationship (EPCR) values. Model performance was determined by two metrics, a weighted score based on the rank position of causal variants, and the maximum F-measure, based on precision and recall of causal variants across all EPCR values. Results Sixteen teams submitted predictions from 52 models, some with manual review incorporated. Top performers recalled causal variants in up to 13 of 14 solved families within the top 5 ranked variants. Newly discovered diagnostic variants were returned to two previously unsolved families following confirmatory RNA sequencing, and two novel disease gene candidates were entered into Matchmaker Exchange. In one example, RNA sequencing demonstrated aberrant splicing due to a deep intronic indel in ASNS, identified in trans with a frameshift variant in an unsolved proband with phenotypes consistent with asparagine synthetase deficiency. Conclusions Model methodology and performance was highly variable. Models weighing call quality, allele frequency, predicted deleteriousness, segregation, and phenotype were effective in identifying causal variants, and models open to phenotype expansion and non-coding variants were able to capture more difficult diagnoses and discover new diagnoses. Overall, computational models can significantly aid variant prioritization. For use in diagnostics, detailed review and conservative assessment of prioritized variants against established criteria is needed.

In this lesson, you will learn how to download YouTube video comments and use the R programming language to analyze the dataset with Wordfish, an algorithm designed to identify opposing ideological perspectives within a corpus.

Background: Evaluation theory has and continues to play an important role in the practice and profession of evaluation. Over the years, and as the range of evaluation theories has continued to grow, evaluation scholars and practitioners have developed various visualized classification frameworks of evaluation theory, invoking images such as trees, rivers, the periodic table, metro maps, concept maps, and most recently gardens. Purpose: The purpose of this special issue is to explore different visualizations of evaluation theory and to discuss their benefits and implications for the practice and profession of evaluation. Setting: Not applicable. Intervention: Not applicable. Research Design: Not applicable. Data Collection and Analysis: Not applicable. Findings: Not applicable. Keywords: Evaluation theory, data visualization, research on evaluation, teaching evaluation

Background: The practice and profession of evaluation continue to evolve. Over the years, evaluation scholars and practitioners have developed a broad—and still broadening—range of evaluation approaches. These evaluation approaches are often combined with various study designs in real-world evaluations. To provide an overview of these approaches and designs, and inspired by my son’s love of metro trains, I created an evaluation metro map. Purpose: The purpose of this article is to describe the background, purpose, and benefits and limitations of the evaluation metro map. Setting: Not applicable Intervention: Not applicable Research Design: Not applicable Data Collection and Analysis: Not applicable Findings: Not applicable Keywords:

Limited data are available for the occurrence of more recent per and polyfluorinated alkyl substances (PFAS) in marine mammals, especially from the St. Lawrence Estuary and Gulf. This study investigates the occurrence of PFAS in liver and muscle tissues of various marine mammals, including the harbor seal, gray seal, harp seal, hooded seal, harbor porpoise, white-sided dolphin, white-beaked dolphin, and True’s beaked whale. Among the 80 target PFAS (including PFCAs, PFSAs, Cyclic PFSA, FASAs/FASAAs, FTCAs/FTUCAs, FTSAs, Ether-PFAS, diPAPs, and ESI + ECF precursors) perfluorooctanoic sulfonate (PFOS) dominates in all the marine mammal species and several other long-chain PFCAs, such as PFNA, PFDA, PFUnA, PFTrDA, and PFHxDA, were detected at 100% frequency in both muscle and liver samples. PFDoA and 7:3 fluorotelomer carboxylic acid (7:3 acid) also showed a 100% detection frequency for liver samples. Harp seal tissues displayed notably low PFAS concentrations, with average total PFAS concentrations of 7 ng/g (ww: wet weight) in muscle and 44 ng/g (ww) in the liver. In contrast, the white-sided dolphin exhibited the highest average concentrations, reaching 39 ng/g (ww) in muscle and 334 ng/g (ww) in liver samples. The Pearson correlation analysis reveals a strong correlation between the concentration of PFOS, perfluoroalkyl carboxylic acids (PFCAs), and electrochemical fluorination (ECF) precursors. Species at the top of the marine food chain (harbor porpoise, white sided dolphin, and white beaked dolphin) presented the highest concentrations of PFAS, particularly PFOS and long-chain PFCAs, highlighting the need for an increased regulation of these persistent molecules in order to protect marine mammal’s health.