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Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.
Methods
In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.
Results
The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).
Conclusions
Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.
Astrobiology is a scientific field that is very interdisciplinary and developing very fast, with many new discoveries generating a high level of attention in both the scientific community and the public. A central goal of astrobiology is to discover life beyond Earth which is, with our current instrumentation and knowledge, arguably within our reach. However, knowledge exchange crossing disciplinary boundaries is becoming increasingly challenging due to different usage of nomenclature and scientific controversies often limited to subdisciplines. There have been some efforts to compile organized databases of terms, concepts and other relevant material within some of the subfields contributing to astrobiology, for example through manually curated online portals designed to benefit students, teachers and practitioners of astrobiology-related research. However, the developments within the subfields and the potentially premature communication of research findings are too fast for objective research portals to remain reliable and up-to-date enough to enable well-informed scientific discussions. We suggest here a novel strategy for developing an online tracers portal as a self-maintaining and self-updating information platform, that would allow not only for a relatively unbiased selection of research results, but also provide fast access to latest scientific discoveries together with potential controversies, such that users of the tracers portal can form their own opinion on all available data rather than obtaining an already filtered and potentially biased selection of information.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
To evaluate performance of registered nurse assessments of the PEN-FAST penicillin allergy clinical decision rule compared to antimicrobial stewardship pharmacists.
This study took place across 4 inpatient hospitals within a large health system in Houston, Texas.
Methods:
We implemented PEN-FAST rule questions into the electronic health record (EHR) for registered nurses to perform. Patients were randomly selected in a prospective fashion, with nurse documented scores hidden, for re-assessment by antimicrobial stewardship pharmacists to compare risk stratification and scores.
Results:
Overall agreement of high risk and low risk results was 84.3%. Registered nurse evaluations with the PEN-FAST clinical decision rule for detecting a high-risk patient demonstrated a sensitivity of 67%, specificity of 89.8%, positive predictive value of 67.9%, and negative predictive value of 89.5%. Additionally, 34.4% of patients with a documented penicillin allergy admitted to tolerating amoxicillin or amoxicillin/clavulanate since their last recalled reaction to penicillin.
Conclusions:
Registered nurse assessment of the PEN-FAST clinical decision rule demonstrated good performance and can effectively be used to screen for low-risk penicillin allergy patients. Incorporation of the PEN-FAST rule into EHR can be scaled into large health systems to help appropriately stratify patients with low- and high-risk penicillin allergies and improve documentation.
Macroscopic, modular, morphologically simple skeletons occur in the uppermost Mural Formation (Cambrian, Epoch 2, Bonnia–Olenellus Biozone), west-central Alberta and adjacent east-central British Columbia. They represent organisms that lived almost exclusively in reefal environments dominated by archaeocyaths. Some were attached to archaeocyaths or less commonly other surfaces, and some grew downward, apparently from overhangs or cavities in reefs. Qualitative and quantitative data from a large number of specimens, most of which were serially thin sectioned, indicate that they represent a single, remarkably variable species. The skeletal structure ranges among specimens from entirely cerioid to partially to entirely labyrinthine with irregularly incomplete walls. There is also a wide range of variability in growth form among skeletons, in module size and wall thickness among and within skeletons, in module shape within skeletons, and in number and location of projections extending from the wall into some modules. Module increase occurred by peripheral expansion at the basal surface of the skeleton and longitudinal fission involving projections from the wall as module size increased during vertical growth. Walls of skeletons, now composed of calcite cement, were probably originally aragonite. Modular skeletons from the uppermost Mural Formation are assigned to Rosellatana jamesi Kobluk, 1984a, previously represented only by a few cerioid specimens from correlative strata in the Rosella Formation of north-central British Columbia. The skeletal structure and types of module increase in R.jamesi, and a few similar but less well-known Cambrian taxa from elsewhere in North America, suggest a general biologic affinity with hypercalcified sponges.
Background: Epstein-Barr virus (EBV) infection is believed to be a critical prerequisite for the development of multiple sclerosis (MS). This study aims to investigate whether anti-EBV titres are elevated before the onset of MS symptoms in people with radiologically isolated syndrome (pwRIS) and to evaluate their association with markers of adverse clinical outcomes. Methods: Epstein-Barr nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA) titres were quantified in a cohort of 47 pwRIS and 24 healthy controls using Enzyme-Linked Immuno-Sorbent Assay. Plasma glial fibrillary acidic protein (GFAP) and neurofilament light protein (NfL) were measured using single-molecule array. MRI lesion metrics and the development of MS symptoms over time were also evaluated. Results: EBNA1 titres were higher pwRIS compared to healthy controls (p=0.038), while VCA titres were not (p=0.237). A positive correlation was observed between EBNA1 titres and plasma GFAP in pwRIS (p=0.005). Neither EBNA1 nor VCA titres correlated with NfL. MRI lesion measures and the development of MS symptoms did not show any significant relationship with EBNA1 or VCA titres. Conclusions: Eelevated EBNA1 titres are detectable prior to MS symptom onset and correlate with GFAP, a biomarker associated with worse clinical outcomes. However, their role in disease progression and clinical outcomes requires further investigation.
Background: Radiologically isolated syndrome (RIS) is characterized by incidental MRI findings suggestive of multiple sclerosis in asymptomatic individuals. Emerging blood biomarkers, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and chitinase 3-like 1 protein (CHI3L1) are promising tools for evaluating neuroinflammation and neurodegeneration. Methods: This cross-sectional analysis included 47 individuals with RIS who underwent MRI and plasma biomarker assessments. Plasma levels of CHI3L1, NfL, and GFAP were measured using highly sensitive assays. Correlations between biomarkers and MRI markers, including T1-black holes (BHs), central vein sign (CVS) positive lesions, paramagnetic rim lesions (PRLs), choroid plexus volume (CPV), and thalamic and hippocampal volumes, were analyzed using linear regression. Results: Plasma CHI3L1 levels correlated with increased CPV (β = 0.347, p = 0.017) and reduced thalamic (β = -0.309, p = 0.035) and hippocampal (β = -0.535, p < 0.001) volumes. Plasma GFAP levels were associated with BHs, CVS, and PRLs, whereas plasma NfL showed no correlations with MRI measures. Conclusions: Plasma CHI3L1 correlates with subcortical grey matter atrophy and CPV increase in RIS, distinct from correlations observed with GFAP or NfL. This suggests that plasma CHI3L1 may reflect neurodegeneration and inflammation in RIS and provide insights into disease activity not captured by other biomarkers.
Background: In multiple sclerosis (MS), soluble mediators of neuroinflammation are released by activated lymphocytes and resident immune cells, leading to demyelination and neurodegeneration. Radiologically isolated syndrome (RIS) is an entity in which white matter lesions fulfilling criteria for MS occur in individuals without any suggestive symptoms. The exact nature of pro- and anti-inflammatory cytokines in blood, and their association with disease activity in RIS/MS requires further clarification. Methods: Plasma was collected and cryopreserved from healthy controls (HCs), people with RIS and relapsing-remitting MS (RRMS) at the Barlo MS Centre. All samples were analyzed with OLink Target 96 Inflammation Multiplex Immunoassay Panel. Results: Individuals with RIS (p=0.0001; p= 0.0007; p= 0.0012) and RRMS (p<0.0001; p= 0.0003; p= 0.00112) had significantly higher concentrations of hepatocyte growth factor (HGF), interleukin-6 (IL-6), and chemokine ligand 23 (CCL23) in plasma compared to HCs, and patients with RRMS (p=0.0087) had significantly higher concentrations of HGF compared to individuals with RIS. Conclusions: Our study demonstrates that HGF, IL-6 and CCL23 are significantly increased in the plasma of patients with RIS and RRMS compared to HCs. Our observations suggest that the biology of MS is present in those with RIS, and these neuroinflammatory mediators may serve as a biomarker of disease activity.
The Child Opportunity Index is an index of 29 indicators of social determinants of health linked to the United States of America Census. Disparities in the treatment of Wolff–Parkinson–White have not be reported. We hypothesise that lower Child Opportunity Index levels are associated with greater disease burden (antiarrhythmic use, ablation success, and Wolff–Parkinson–White recurrence) and ablation utilisation.
Methods:
A retrospective, single-centre study was performed with Wolff–Parkinson–White patients who received care from January 2021 to July 2023. Following exclusion for <5 years old and with haemodynamically significant CHD, 267 patients were included (45% high, 30% moderate, and 25% low Child Opportunity Index). Multi-level logistic and log-linear regression was performed to assess the relationship between Child Opportunity Index levels and outcomes.
Results:
Low patients were more likely to be Black (p < 0.0001) and to have public insurance (p = 0.0006), though, there were no significant differences in ablation utilisation (p = 0.44) or time from diagnosis to ablation (p = 0.37) between groups. There was an inverse relationship with emergency department use (p = 0.007). The low group had 2.8 times greater odds of having one or more emergency department visits compared to the high group (p = 0.004).
Conclusion:
The Child Opportunity Index was not related with ablation utilisation, while there was an inverse relationship in emergency department use. These findings suggest that while social determinants of health, as measured by Child Opportunity Index, may influence emergency department utilisation, they do not appear to impact the overall management and procedural timing for Wolff–Parkinson–White treatment.
Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) can treat suicidal symptoms; however, the effects of rTMS on suicidal ideation (SI) in late-life depression (LLD) have not been well-characterized, particularly with theta burst stimulation (TBS).
Methods
Data were analyzed from 84 older adults with depression from the FOUR-D trial (ClinicalTrials.gov identifier: NCT02998580), who received either bilateral standard rTMS or bilateral TBS targeting the dorsolateral prefrontal cortex. The primary outcome was change in the Beck Scale for Suicide Ideation (SSI). The secondary outcome was remission of SI. Demographic, cognitive, and clinical characteristics that may moderate the effects of rTMS or TBS on SI were explored.
Results
There was a statistically significant change in the total SSI score over time [χ2(7) = 136.018, p < 0.001], with no difference between the two treatment groups. Remission of SI was 55.8% in the standard rTMS group and 53.7% in the TBS group. In the standard rTMS group, there was no difference in remission of SI between males and females, whereas remission was higher in females in the TBS group (χ2(1) =6.87, p = 0.009). There was a significant correlation between time to remission of SI and RCI z-score for D-KEFS inhibition/switching [rs = −0.389, p = 0.012].
Conclusions
Both bilateral rTMS and bilateral TBS were effective in reducing SI in LLD. There may be sex differences in response to TBS, with females having more favorable response in reducing SI. There may be an association between improvement in cognitive flexibility and inhibition and reduction of SI.
Depression is a complex mental health disorder with highly heterogeneous symptoms that vary significantly across individuals, influenced by various factors, including sex and regional contexts. Network analysis is an analytical method that provides a robust framework for evaluating the heterogeneity of depressive symptoms and identifying their potential clinical implications.
Objective:
To investigate sex-specific differences in the network structures of depressive symptoms in Asian patients diagnosed with depressive disorders, using data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, Phase 3, which was conducted in 2023.
Methods:
A network analysis of 10 depressive symptoms defined according to the National Institute for Health and Care Excellence guidelines was performed. The sex-specific differences in the network structures of the depressive symptoms were examined using the Network Comparison Test. Subgroup analysis of the sex-specific differences in the network structures was performed according to geographical region classifications, including East Asia, Southeast Asia, and South or West Asia.
Results:
A total of 998 men and 1,915 women with depression were analysed in this study. The analyses showed that all 10 depressive symptoms were grouped into a single cluster. Low self-confidence and loss of interest emerged as the most central nodes for men and women, respectively. In addition, a significant difference in global strength invariance was observed between the networks. In the regional subgroup analysis, only East Asian men showed two distinct clustering patterns. In addition, significant differences in global strength and network structure were observed only between East Asian men and women.
Conclusion:
The study highlights the sex-specific differences in depressive symptom networks across Asian countries. The results revealed that low self-confidence and loss of interest are the main symptoms of depression in Asian men and women, respectively. The network connections were more localised in men, whereas women showed a more diverse network. Among the Asian subgroups analysed, only East Asians exhibited significant differences in network structure. The considerable effects of neurovegetative symptoms in men may indicate potential neurobiological underpinnings of depression in the East Asian population.
Early Miocene land mammals from eastern North America are exceedingly rare. Over the past several decades a small, but significant, vertebrate fauna has been recovered by paleontologists and citizen scientists from the Belgrade Formation at the Martin Marietta Belgrade Quarry in eastern North Carolina. This assemblage has 12 land mammal taxa, including beaver (Castoridae), stem lagomorph, carnivorans (Mustelidae, Ailuridae), horses (Equidae), rhinoceros (Rhinocerotidae), tapir (Tapiridae), peccary (Tayassuidae), anthracothere (Anthracotheriidae), entelodont (Entelodontidae), and protoceratid (Protoceratidae). Taken together, the biochronology of this Maysville Local Fauna indicates a late Arikareean (Ar3/Ar4) to early Hemingfordian (He1) North American Land Mammal Age (NALMA). This interval, which includes the Runningwater Chronofauna, documents numerous important Holarctic immigrants, including Amphictis, Craterogale, and cf. Menoceras found at this locality. Strontium isotope stratigraphy (SIS) of shark teeth collected in situ from the Belgrade Formation yield an age of 21.4 ± 0.13 Ma, which validates the age of interbedded land mammals within this unit. It also is consistent with the late Arikareean (Ar3/Ar4) biochronology and Aquitanian Neogene marine stage. New SIS analyses of oysters (Striostrea gigantissima) and clams (Chione) from this mine, previously assigned to late Oligocene or Late Miocene, are significantly older (28.0 ± 0.22 Ma and 27.6 ± 0.26 Ma, respectively) than the land mammals. Depending upon stratigraphic interpretations, these may confirm an older marine facies within the Belgrade Formation. This locality is important because of its marine and terrestrial tie-ins that facilitate intercalibration of both NALMAs and Cenozoic marine stages.
Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.
The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.
The New York Philharmonic Orchestra performed in North Korea on February 25 to much international attention – and controversy. When news of an invitation from the Democratic People's Republic of Korea (DPRK, the official name of North Korea) surfaced last fall, it ignited a storm of North Korea-bashing as well as hope in some quarters for a breakthrough in DPRK-US relations modeled on the ping pong diplomacy that jump-started US-China relations earlier. The media coverage of the event recapitulated the regime change vs. engagement debates argued in the security realm. After examining the background to the events in Pyongyang, this article assesses Western responses to the proposed visit and its potential significance for the US-North Korea relationship.
Adolescence is a key developmental period associated with an increased risk of experiencing cannabis-related problems. Identifying modifiable risk factors prior to the onset of cannabis use could help inform preventative interventions.
Method
Analysis nested within a UK prospective birth cohort study, the Avon Longitudinal Study of Parents and Children. Participants (n = 6,049) provided data on cannabis use and symptoms of cannabis problems using the Cannabis Abuse Screening Test at two or more time points between the ages of 15–24 years. Risk factors included internalizing and externalizing disorders assessed at age 10 years, and cognitive function assessed at age 8 years via short-term memory, emotion recognition, divided attention, and listening comprehension.
Results
Participants were mostly female (59.1%) and white (95.73%). Five patterns of adolescent cannabis use problems were identified using longitudinal latent class analysis: stable-no problems (n = 5,157, 85%), early-onset high (n = 104, 2%), late-onset high (n = 153, 3%), early onset low (n = 348, 6%), and late-onset low (n = 287, 5%). In adjusted models, externalizing disorders were associated with early-onset high [RR, 95% CI: 2.82 (1.72, 4.63)], late-onset high [RR, 95% CI: 1.62 (1.02, 2.57)], and early-onset low [RR, 95% CI: 1.82 (1.30, 2.55)] compared to the stable-no problems class. Internalizing disorders were associated with late-onset low only [RR, 95% CI: .50 (.26, .96)], and short-term memory with late-onset high only [RR, 95% CI: 1.09 (1.01, 1.18) compared to the stable-no problems class.
Conclusions
Childhood externalizing disorders were consistently associated with increased risk of problematic patterns of cannabis use over adolescence, particularly early-onset and high levels of problems.
Objectives/Goals: Manual skin assessment in chronic graft-versus-host disease (cGVHD) can be time consuming and inconsistent (>20% affected area) even for experts. Building on previous work we explore methods to use unmarked photos to train artificial intelligence (AI) models, aiming to improve performance by expanding and diversifying the training data without additional burden on experts. Methods/Study Population: Common to many medical imaging projects, we have a small number of expert-marked patient photos (N = 36, n = 360), and many unmarked photos (N = 337, n = 25,842). Dark skin (Fitzpatrick type 4+) is underrepresented in both sets; 11% of patients in the marked set and 9% in the unmarked set. In addition, a set of 20 expert-marked photos from 20 patients were withheld from training to assess model performance, with 20% dark skin type. Our gold standard markings were manual contours around affected skin by a trained expert. Three AI training methods were tested. Our established baseline uses only the small number of marked photos (supervised method). The semi-supervised method uses a mix of marked and unmarked photos with human feedback. The self-supervised method uses only unmarked photos without any human feedback. Results/Anticipated Results: We evaluated performance by comparing predicted skin areas with expert markings. The error was given by the absolute difference between the percentage areas marked by the AI model and expert, where lower is better. Across all test patients, the median error was 19% (interquartile range 6 – 34) for the supervised method and 10% (5 – 23) for the semi-supervised method, which incorporated unmarked photos from 83 patients. On dark skin types, the median error was 36% (18 – 62) for supervised and 28% (14 – 52) for semi-supervised, compared to a median error on light skin of 18% (5 – 26) for supervised and 7% (4 – 17) for semi-supervised. Self-supervised, using all 337 unmarked patients, is expected to further improve performance and consistency due to increased data diversity. Full results will be presented at the meeting. Discussion/Significance of Impact: By automating skin assessment for cGVHD, AI could improve accuracy and consistency compared to manual methods. If translated to clinical use, this would ease clinical burden and scale to large patient cohorts. Future work will focus on ensuring equitable performance across all skin types, providing fair and accurate assessments for every patient.
Objectives/Goals: Team science (TS) competency is important for translational science team collaboration. However, there are few educators available to assist teams. Asynchronous learning is an effective strategy for delivering TS content. The goal of this project is to expand TS education by providing online access to our learners using online modules. Methods/Study Population: The Collaboration and Team Science (CaTS) team at the University of Cincinnati provides a robust TS education and training program. As the need for team science gains recognition, CaTS has received increased requests for services, leading to a need to broaden TS offerings. To address this demand, the CaTS team created “Team Science 101,” an online, asynchronous, series of 15 modules covering basic team science concepts. Each module consists of an educational recording lasting an average of 20 minutes, optional topic resources, pre- and post-module surveys assessing learners’ confidence and satisfaction, post-module knowledge checks, and evaluation questions. Upon completing all modules, participants receive a completion certificate. Results/Anticipated Results: TS 101 will be piloted with a group of participants who expressed interest in asynchronous TS content and will be adjusted based on the feedback received. The associated pre- and post-module survey, post-module knowledge check, and evaluation questions will be monitored to determine learning levels and improve TS 101 overall. Canvas is the educational platform that houses these modules, allowing for participant follow-up and scalable dissemination. The CaTS team plans to disseminate TS 101 nationally and internationally for anyone interested in this resource. Discussion/Significance of Impact: There is a national effort to collect and curate TS education, training, and toolkits. TS 101 will be a useful educational tool that will expand the reach of team science educators, provide the foundation for educators to explore topics more deeply by building on the module topics, and provide education to broader audiences who lack access to TS experts.