Intra-Host Evolution Analyses in an Immunosuppressed Patient Supports SARS-CoV-2 Viral Reservoir Hypothesis.

Throughout the SARS-CoV-2 pandemic, several variants of concern (VOCs) have been identified, many of which share recurrent mutations in the spike glycoprotein's receptor-binding domain (RBD). This region coincides with known epitopes and can therefore have an impact on immune escape. Protracted infections in immunosuppressed patients have been hypothesized to lead to an enrichment of such mutations and therefore drive evolution towards VOCs. Here, we present the case of an immunosuppressed patient that developed distinct populations with immune escape mutations throughout the course of their infection. Notably, by investigating the co-occurrence of substitutions on individual sequencing reads in the RBD, we found quasispecies harboring mutations that confer resistance to known monoclonal antibodies (mAbs) such as S:E484K and S:E484A. These mutations were acquired without the patient being treated with mAbs nor convalescent sera and without them developing a detectable immune response to the virus. We also provide additional evidence for a viral reservoir based on intra-host phylogenetics, which led to a viral substrain that evolved elsewhere in the patient's body, colonizing their upper respiratory tract (URT). The presence of SARS-CoV-2 viral reservoirs can shed light on protracted infections interspersed with periods where the virus is undetectable, and potential explanations for long-COVID cases.

A critical review of the role of manual therapy in the treatment of individuals with low back pain.

The number of low back pain (LBP) cases is projected to increase to more than 800 million by 2050. To address the substantial burden of disease associated with this rise in prevalence, effective treatments are needed. While clinical practice guidelines (CPG) consistently recommend non-pharmacological therapies as first-line treatments, recommendations regarding manual therapy (MT) in treating low back pain vary. The goal of this narrative review was to critically summarize the available evidence for MT behind these recommendations, to scrutinize its mechanisms of action, and propose some actionable steps for clinicians on how this knowledge can be integrated into a person-centered approach. Despite disparate recommendations from CPG, MT is as effective as other available treatments and may be offered to patients with LBP, especially as part of a treatment package with exercise and education. Most of the effects of MT are not specific to the technique. MT and other interventions share several mechanisms of action that mediate treatment success. These mechanisms can encompass patients' expectations, prior experiences, beliefs and convictions, epistemic trust, and nonspecific contextual effects. Although MT is safer than opioids for patients with LBP, this alone is insufficient. Our goal is to encourage clinicians to shift away from outdated and refuted ideas in MT and embrace a person-centered approach rooted in a comprehensive biopsychosocial framework while incorporating patients' beliefs, addressing illness behaviors, and seeking to understand each patient's journey.

Signatures of Co-evolution and Co-regulation in the CYP3A and CYP4F Genes in Humans.

Cytochromes P450 (CYP450) are hemoproteins generally involved in the detoxification of the body of xenobiotic molecules. They participate in the metabolism of many drugs and genetic polymorphisms in humans have been found to impact drug responses and metabolic functions. In this study, we investigate the genetic diversity of CYP450 genes. We found that two clusters, CYP3A and CYP4F, are notably differentiated across human populations with evidence for selective pressures acting on both clusters: we found signals of recent positive selection in CYP3A and CYP4F genes and signals of balancing selection in CYP4F genes. Furthermore, an extensive amount of unusual linkage disequilibrium is detected in this latter cluster, indicating co-evolution signatures among CYP4F genes. Several of the selective signals uncovered co-localize with expression quantitative trait loci (eQTL), which could suggest epistasis acting on co-regulation in these gene families. In particular, we detected a potential co-regulation event between CYP3A5 and CYP3A43, a gene whose function remains poorly characterized. We further identified a causal relationship between CYP3A5 expression and reticulocyte count through Mendelian randomization analyses, potentially involving a regulatory region displaying a selective signal specific to African populations. Our findings linking natural selection and gene expression in CYP3A and CYP4F subfamilies are of importance in understanding population differences in metabolism of nutrients and drugs.

Antiracist training programs for mental health professionals: A scoping review.

Racism has been shown to be directly deleterious to the mental health care received by minoritized peoples. In response, some mental health institutions have pledged to provide antiracist mental health care, which includes training mental health care professionals in this approach. This scoping review aimed to synthesize the existing published material on antiracist training programs among mental health care professionals. To identify studies, a comprehensive search strategy was developed and executed by a research librarian in October 2022 across seven databases (APA PsycInfo, Education Source, Embase, ERIC, MEDLINE, CINAHL, and Web of Science). Subject headings and keywords relating to antiracist training as well as to mental health professionals were used and combined. There were 7186 studies generated by the initial search and 377 by the update search, 30 were retained and included. Findings revealed four main antiracist competencies to develop in mental health professionals: importance of understanding the cultural, social, and historical context at the root of the mental health problems; developing awareness of individual biases, self-identity and privilege; recognizing oppressive and racism-sustaining behaviors in mental health care settings; and, employing antiracist competencies in therapy. Professionals who have taken trainings having the main components have developed skills on the interconnectedness between racialized groups' mental health and the cultural, religious, social, historical, economic, and political issues surrounding race, necessary for successful clinical practice and for providing anti-racist mental health care. This scoping review presents a summary of the essential antiracist competencies drawn from the literature which must be applied in a mental health care setting, to improve help seeking behaviors, and reduce distrust in mental health care professionals and settings.

Toward computing attributions for dimensionality reduction techniques.

Summary: We describe the problem of computing local feature attributions for dimensionality reduction methods. We use one such method that is well established within the context of supervised classification-using the gradients of target outputs with respect to the inputs-on the popular dimensionality reduction technique t-SNE, widely used in analyses of biological data. We provide an efficient implementation for the gradient computation for this dimensionality reduction technique. We show that our explanations identify significant features using novel validation methodology; using synthetic datasets and the popular MNIST benchmark dataset. We then demonstrate the practical utility of our algorithm by showing that it can produce explanations that agree with domain knowledge on a SARS-CoV-2 sequence dataset. Throughout, we provide a road map so that similar explanation methods could be applied to other dimensionality reduction techniques to rigorously analyze biological datasets. Availability and implementation: We have created a Python package that can be installed using the following command: pip install interpretable_tsne. All code used can be found at github.com/MattScicluna/interpretable_tsne.

Selection for immune evasion in SARS-CoV-2 revealed by high-resolution epitope mapping and sequence analysis.

Here, we exploit a deep serological profiling strategy coupled with an integrated, computational framework for the analysis of SARS-CoV-2 humoral immune responses. Applying a high-density peptide array (HDPA) spanning the entire proteomes of SARS-CoV-2 and endemic human coronaviruses allowed identification of B cell epitopes and relate them to their evolutionary and structural properties. We identify hotspots of pre-existing immunity and identify cross-reactive epitopes that contribute to increasing the overall humoral immune response to SARS-CoV-2. Using a public dataset of over 38,000 viral genomes from the early phase of the pandemic, capturing both inter- and within-host genetic viral diversity, we determined the evolutionary profile of epitopes and the differences across proteins, waves, and SARS-CoV-2 variants. Lastly, we show that mutations in spike and nucleocapsid epitopes are under stronger selection between than within patients, suggesting that most of the selective pressure for immune evasion occurs upon transmission between hosts.

Relationship satisfaction and psychological wellbeing in men having participated in the MindTheHeart® psychoeducation intervention after an acute coronary syndrome.

This study investigated the associations of relationship satisfaction, depression, and anxiety post-acute coronary syndrome in a sample of men having completed an early, couple-focused, and men-tailored psychoeducation intervention. A baseline sample of 50 male patients were followed over a 12-month period and completed the Couples Satisfaction Index and the Depression, Anxiety and Stress Scale. Results revealed a significant improvement in depression symptoms from T0 to T1, during which all participants completed the MindTheHeart® psychoeducation intervention. In addition, a hierarchical regression analysis showed that relationship satisfaction is an important predictor of this improvement in depression symptoms. Our preliminary findings point to the consideration of life partners in post-ACS interventions and encourage the exploration of this clinical approach in future research.

Reply to Barton et al: signatures of natural selection during the Black Death.

Barton et al.1 raise several statistical concerns regarding our original analyses2 that highlight the challenge of inferring natural selection using ancient genomic data. We show here that these concerns have limited impact on our original conclusions. Specifically, we recover the same signature of enrichment for high FST values at the immune loci relative to putatively neutral sites after switching the allele frequency estimation method to a maximum likelihood approach, filtering to only consider known human variants, and down-sampling our data to the same mean coverage across sites. Furthermore, using permutations, we show that the rs2549794 variant near ERAP2 continues to emerge as the strongest candidate for selection (p = 1.2×10-5), falling below the Bonferroni-corrected significance threshold recommended by Barton et al. Importantly, the evidence for selection on ERAP2 is further supported by functional data demonstrating the impact of the ERAP2 genotype on the immune response to Y. pestis and by epidemiological data from an independent group showing that the putatively selected allele during the Black Death protects against severe respiratory infection in contemporary populations.

Controversial Outcomes in Neck Rehabilitation between Surgically and Conservatively Treated Patients-Results of an Observational Study.

The present study aimed to compare changes during inpatient rehabilitation between conservatively and surgically treated patients. A total of n = 162 patients with cervical spine complaints were included in the study (n = 107 conservatively treated, n = 55 after surgery). Patients completed disease-specific (NDI) and generic (NPRS, EQ-5D-5L, HAQ) patient reported outcome measures (PROMs) before and after rehabilitation. In addition, the range of motion (ROM) in the transversal plane of the cervical spine was measured. Changes and correlations between PROMs and ROM values during rehabilitation were assessed. The influence of moderating factors on NDI outcomes was examined. Significant improvements with large effect sizes were found in PROMs and ROM (all p < 0.001). The conservatively treated patients showed significantly greater NDI improvements than operated patients (p = 0.050), but a greater proportion of poor performance in ROM (p = 0.035). Baseline NDI (ß = 0.66), HAQ (ß = 0.14), and ROM scores (ß = -0.17) explained 63.7% of the variance in NDI after rehabilitation. Both patient groups showed different outcomes. The findings of this study indicate that the unique needs of patients may require different therapeutic interventions and highlight the importance of using multidimensional outcome measures when implementing a multimodal rehabilitation approach.

Study of effect modifiers of genetically predicted CETP reduction.

Genetic variants in drug targets can be used to predict the long-term, on-target effect of drugs. Here, we extend this principle to assess how sex and body mass index may modify the effect of genetically predicted lower CETP levels on biomarkers and cardiovascular outcomes. We found sex and body mass index (BMI) to be modifiers of the association between genetically predicted lower CETP and lipid biomarkers in UK Biobank participants. Female sex and lower BMI were associated with higher high-density lipoprotein cholesterol and lower low-density lipoprotein cholesterol for the same genetically predicted reduction in CETP concentration. We found that sex also modulated the effect of genetically lower CETP on cholesterol efflux capacity in samples from the Montreal Heart Institute Biobank. However, these modifying effects did not extend to sex differences in cardiovascular outcomes in our data. Our results provide insight into the clinical effects of CETP inhibitors in the presence of effect modification based on genetic data. The approach can support precision medicine applications and help assess the external validity of clinical trials.

Modifiable factors influencing length of stay after total knee arthroplasty.

PURPOSE: This cohort study aims to investigate the current Rapid-Recovery-(RR)-pathway at an orthopaedic surgery hospital centre and to identify preoperative, intraoperative, and postoperative factors that are significantly associated with prolonged hospital Length of Stay (LOS) after total knee arthroplasty (TKA). METHOD: A total of 194 patients undergoing primary TKA were included in this retrospective study. Sociodemographic data documented were age, gender, body mass index, living situation, and the clinical diagnosis. Factors affecting patient constitution and laboratory data for serum level of Hb and CRP were assessed preoperatively and postoperatively. In addition, we collected patients' data for attendance of patient education, planned discharge to rehabilitation facilities, and levels of postoperative pain. RESULTS: In univariate group comparisons, prolonged LOS was significantly associated with increased age, elevated C-reactive-Protein-level, and decreased haemoglobin level. Patients experiencing prolonged LOS also showed significant association with higher prevalence of comorbidities, female gender, living as widow, preoperative anticoagulation, requirement of blood transfusion, and planned discharge to rehabilitation facilities. However, after multivariate logistic regression, only planned discharge to rehabilitation facility, non-attendance of preoperative patient education, female gender, and increased pain levels were identified as significant predictors for prolonged LOS. CONCLUSION: Efficient pain therapy and thorough patient education have a positive effect on treatment outcome after TKA in a RR-setting.

Variation in the utilisation of physiotherapy in patients with advanced knee osteoarthritis prior to total knee arthroplasty a systematic review.

INTRODUCTION: Due to demographic changes and increasing knee osteoarthritis (KOA) prevalence, the incidence of total knee arthroplasties (TKA) is constantly rising. Clinical practice guidelines for the treatment of KOA unanimously recommend non-surgical interventions such as exercise, education, and weight reduction in overweight patients. The aim of this systematic review is to determine the proportion of patients with end-stage KOA who attended physiotherapy (PT) prior to TKA. METHODS: A systematic literature search was carried out in the medical databases MEDLINE (via Pubmed), PEDro, and EBSCO in August of 2022. Studies were included regardless of their design, if they reported the proportion of patients with a diagnosis of primary KOA, who participated in PT prior to undergoing TKA. Study quality assessment was performed by two independent authors using the Joanna Briggs Institutes Checklist for studies reporting prevalence data. Results were presented by using a narrative synthesis. RESULTS: Eighteen studies, comprising 579,718 patients, were identified in this systematic review. PT utilisation prior to TKA ranged from 10% to 73% for patients with advanced KOA. Only two studies showed PT utilisation rates of 60% or higher. Female gender, higher income, better socioeconomic status, higher education levels, older age were associated with PT utilisation. Data for other predicting factors was conflicting. DISCUSSION: This review shows substantial variation in the utilisation of PT in patients with end-stage KOA. This is concerning, considering the uniform recommendation from clinical practice guidelines for non-surgical treatments like exercise and education in patients with KOA, which are mostly provided by physiotherapists.

Nutritional quality and greenhouse gas emissions of vegetarian and non-vegetarian primary school meals: A case study in Dijon, France.

Since 2018 in France, national regulation mandates that school canteens serve a weekly vegetarian meal to reduce school canteens' environmental impact in addition to previous regulations imposing nutritional composition guidelines. However, a lunch without meat is often perceived as inadequate to cover the nutritional needs of children. The present study aims to assess the nutritional quality and greenhouse gas emissions (GHGE) of vegetarian and non-vegetarian school meals served in primary schools in Dijon, France. The catering department provided the composition of 249 meals served in 2019. Nutritional content and GHGE were retrieved from national food databases. The portion size of each meal component was the standard portion size recommended by the relevant French authority (GEMRCN). Meals were classified into vegetarian meals, i.e., without meat or fish (n = 66), or non-vegetarian meals (n = 183). The nutritional adequacy of the meals for children aged from 6 to 11 years was estimated using the mean adequacy ratio (MAR/2,000 kcal) as the mean percentage of daily recommended intake for 23 nutrients and the mean excess ratio (MER/2,000 kcal) as the mean percentage of excess compared to the maximum daily recommended value for three nutrients. This analysis of actual school meals shows that both vegetarian and non-vegetarian meals had a similar good nutritional quality with MAR/2,000 kcal of 87.5% (SD 5.8) for vegetarian and of 88.5% (SD 4.5) for non-vegetarian meals, and a MER/2,000 kcal of 19.3% (SD 15.0) for vegetarian and of 19.1% (SD 18.6) for non-vegetarian meals. GHGE were more than twofold reduced in vegetarian compared to non-vegetarian meals (0.9 (SD 0.3) vs. 2.1 (SD 1.0) kgC02 eq/meal). Thus, increasing the frequency of vegetarian meals, by serving egg-based, dairy-based or vegan recipes more frequently, would reduce GHGE while maintaining adequate nutritional quality of primary school meals.

Evolution of immune genes is associated with the Black Death.

Infectious diseases are among the strongest selective pressures driving human evolution1,2. This includes the single greatest mortality event in recorded history, the first outbreak of the second pandemic of plague, commonly called the Black Death, which was caused by the bacterium Yersinia pestis3. This pandemic devastated Afro-Eurasia, killing up to 30-50% of the population4. To identify loci that may have been under selection during the Black Death, we characterized genetic variation around immune-related genes from 206 ancient DNA extracts, stemming from two different European populations before, during and after the Black Death. Immune loci are strongly enriched for highly differentiated sites relative to a set of non-immune loci, suggesting positive selection. We identify 245 variants that are highly differentiated within the London dataset, four of which were replicated in an independent cohort from Denmark, and represent the strongest candidates for positive selection. The selected allele for one of these variants, rs2549794, is associated with the production of a full-length (versus truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and increased ability to control intracellular Y. pestis in macrophages. Finally, we show that protective variants overlap with alleles that are today associated with increased susceptibility to autoimmune diseases, providing empirical evidence for the role played by past pandemics in shaping present-day susceptibility to disease.

Synchrony and idiosyncrasy in the gut microbiome of wild baboons.

Human gut microbial dynamics are highly individualized, making it challenging to link microbiota to health and to design universal microbiome therapies. This individuality is typically attributed to variation in host genetics, diets, environments and medications but it could also emerge from fundamental ecological forces that shape microbiota more generally. Here, we leverage extensive gut microbial time series from wild baboons-hosts who experience little interindividual dietary and environmental heterogeneity-to test whether gut microbial dynamics are synchronized across hosts or largely idiosyncratic. Despite their shared lifestyles, baboon microbiota were only weakly synchronized. The strongest synchrony occurred among baboons living in the same social group, probably because group members range over the same habitat and simultaneously encounter the same sources of food and water. However, this synchrony was modest compared to each host's personalized dynamics. In support, host-specific factors, especially host identity, explained, on average, more than three times the deviance in longitudinal dynamics compared to factors shared with social group members and ten times the deviance of factors shared across the host population. These results contribute to mounting evidence that highly idiosyncratic gut microbiomes are not an artefact of modern human environments and that synchronizing forces in the gut microbiome (for example, shared environments, diets and microbial dispersal) are not strong enough to overwhelm key drivers of microbiome personalization, such as host genetics, priority effects, horizontal gene transfer and functional redundancy.

deepSimDEF: deep neural embeddings of gene products and gene ontology terms for functional analysis of genes.

MOTIVATION: There is a plethora of measures to evaluate functional similarity (FS) of genes based on their co-expression, protein-protein interactions and sequence similarity. These measures are typically derived from hand-engineered and application-specific metrics to quantify the degree of shared information between two genes using their Gene Ontology (GO) annotations. RESULTS: We introduce deepSimDEF, a deep learning method to automatically learn FS estimation of gene pairs given a set of genes and their GO annotations. deepSimDEF's key novelty is its ability to learn low-dimensional embedding vector representations of GO terms and gene products and then calculate FS using these learned vectors. We show that deepSimDEF can predict the FS of new genes using their annotations: it outperformed all other FS measures by >5-10% on yeast and human reference datasets on protein-protein interactions, gene co-expression and sequence homology tasks. Thus, deepSimDEF offers a powerful and adaptable deep neural architecture that can benefit a wide range of problems in genomics and proteomics, and its architecture is flexible enough to support its extension to any organism. AVAILABILITY AND IMPLEMENTATION: Source code and data are available at https://github.com/ahmadpgh/deepSimDEF. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Population Genomics Approaches for Genetic Characterization of SARS-CoV-2 Lineages.

The genome of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), has been sequenced at an unprecedented scale leading to a tremendous amount of viral genome sequencing data. To assist in tracing infection pathways and design preventive strategies, a deep understanding of the viral genetic diversity landscape is needed. We present here a set of genomic surveillance tools from population genetics which can be used to better understand the evolution of this virus in humans. To illustrate the utility of this toolbox, we detail an in depth analysis of the genetic diversity of SARS-CoV-2 in first year of the COVID-19 pandemic. We analyzed 329,854 high-quality consensus sequences published in the GISAID database during the pre-vaccination phase. We demonstrate that, compared to standard phylogenetic approaches, haplotype networks can be computed efficiently on much larger datasets. This approach enables real-time lineage identification, a clear description of the relationship between variants of concern, and efficient detection of recurrent mutations. Furthermore, time series change of Tajima's D by haplotype provides a powerful metric of lineage expansion. Finally, principal component analysis (PCA) highlights key steps in variant emergence and facilitates the visualization of genomic variation in the context of SARS-CoV-2 diversity. The computational framework presented here is simple to implement and insightful for real-time genomic surveillance of SARS-CoV-2 and could be applied to any pathogen that threatens the health of populations of humans and other organisms.

Multiscale PHATE identifies multimodal signatures of COVID-19.

As the biomedical community produces datasets that are increasingly complex and high dimensional, there is a need for more sophisticated computational tools to extract biological insights. We present Multiscale PHATE, a method that sweeps through all levels of data granularity to learn abstracted biological features directly predictive of disease outcome. Built on a coarse-graining process called diffusion condensation, Multiscale PHATE learns a data topology that can be analyzed at coarse resolutions for high-level summarizations of data and at fine resolutions for detailed representations of subsets. We apply Multiscale PHATE to a coronavirus disease 2019 (COVID-19) dataset with 54 million cells from 168 hospitalized patients and find that patients who die show CD16hiCD66blo neutrophil and IFN-γ+ granzyme B+ Th17 cell responses. We also show that population groupings from Multiscale PHATE directly fed into a classifier predict disease outcome more accurately than naive featurizations of the data. Multiscale PHATE is broadly generalizable to different data types, including flow cytometry, single-cell RNA sequencing (scRNA-seq), single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq), and clinical variables.

Recommendations for virtual care in primary care practices: a survey of patients across Ontario, Canada.

Context: The onset of COVID-19 has required the rapid adoption of virtual services in primary care (PC) practices, and virtual care delivery is likely to continue to some extent post-pandemic. Objective: To understand patient experience with synchronous virtual (telephone (Tel)/Video) appointments and elicit recommendations for its future use. Design: Mixed method, including patient survey co-developed with stakeholders and implemented online Feb-Mar 2021 with large promotional efforts through social media, patient and caregiver organizations, and other networks. We report on the survey results. Eligibility: 1+ virtual encounter in PC. Outcome measures: A) Patient experience scale (12/17 questions for Tel/Video) covering 4 sub-dimensions; B) Access related questions. Questions had 5-point Likert scale items (strongly disagree (-2) to strongly agree (+2)) and were converted into percentage (potential range -100%, +100%) Setting : Ontario, Canada which offers universal coverage for PC visits with no co-payment. Results: 534 eligible respondents (402/18/114 had Tel/Video/both): Females (78%), < 55 years (61%), white (75%), employed (61%), bachelor's degree (74%), family income > 100k (52%). Encounters evaluated were with family physicians (vs other health professionals) for 75%/46% of Tel/Video encounters. A) Patient Experience (Tel/Video) overall score: 75%/78%; Sub-dimensions: technology: 92%/84%, patient-provider relationship: 83%/86%, quality of care: 66%/66%, whole-person care: 43%/53%. Factors associated with a statistically significant(*) > 10% higher overall score in tel and/or video were: non-females: (8%*/14%*), French speaking (13%*/16%*), patient-provider relationship >1 year (16%*/7%), provider age < 50 (5%/15%*), having the choice of appointment time (15%*/21%*). Wanting to show problem to the provider was associated with a lower scores (-23%*/NA). B) Access Respondents overwhelmingly reported that Tel/Video visits reduced time (97%/97%), costs (81%/85%), and was more convenient (91%/91%). The majority wanted Tel (69%) and Video (71%) visits at least as often as in person visits post-covid. Only 5% did not want any future virtual care. Conclusions: Patient experience was largely positive and is influenced by patient/provider factors. Patients and providers may benefit from support/training to optimize care experience. We are now evaluating whether the reasons for visits influences care experience.

Exploring Mental Health Professionals' Experiences of Intimate Partner Violence-Related Training: Results From a Global Survey.

Intimate partner violence (IPV) is a global public health problem that has been shown to lead to serious mental health consequences. Due to its frequent co-occurrence with psychiatric disorders, it is important to assess for IPV in mental health settings to improve treatment planning and referral. However, lack of training in how to identify and respond to IPV has been identified as a barrier for the assessment of IPV. The present study seeks to better understand this IPV-related training gap by assessing global mental health professionals' experiences of IPV-related training and factors that contribute to their likelihood of receiving training. Participants were French-, Spanish-, and Japanese-speaking psychologists and psychiatrists (N = 321) from 24 nations differing on variables related to IPV, including IPV prevalence, IPV-related norms, and IPV-related laws. Participants responded to an online survey asking them to describe their experiences of IPV-related training (i.e., components and hours of training) and were asked to rate the frequency with which they encountered IPV in clinical practice and their level of knowledge and experience related to relationship problems; 53.1% of participants indicated that they had received IPV-related training. Clinicians from countries with relatively better implemented laws addressing IPV and those who encountered IPV more often in their regular practice were more likely to have received training. Participants who had received IPV-related training, relative to those without training, were more likely to report greater knowledge and experience related to relationship problems. Findings suggest that clinicians' awareness of IPV and the institutional context in which they practice are related to training. Training, in turn, is associated with subjective appraisals of knowledge and experience related to relationship problems. Increasing institutional efforts to address IPV (e.g., implementing IPV legislation) may contribute to improved practices with regard to IPV in mental health settings.