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Objective: Poorly differentiated thyroid carcinomas (PDTCs) are rare and aggressive head and neck malignancies with a poor prognosis. Systemic treatment for incurable PDTC consists of multi-kinase inhibitors (MKIs) based on extrapolation from the experience with radioiodine refractory differentiated thyroid cancer (DTC). Cabozantinib is an approved second-line MKI therapy for DTC, but there are limited data regarding the safety and efficacy of cabozantinib for PDTC. Methods: We conducted a single-institution, retrospective analysis of patients with PDTC who received cabozantinib in any line of therapy. Baseline demographics, disease characteristics, treatment history, toxicity, and clinical outcomes were abstracted from the electronic medical record. Median progression-free survival (PFS) and overall survival (OS) were primary endpoints and estimated using Kaplan–Meier methodology. Results: Seven patients with PDTC who received cabozantinib were included. 4/7 (57%) patients had a partial response to cabozantinib, while 2/7 (29%) had stable disease (SD) as their best response. The median time on treatment for cabozantinib was 10.53 months. The median PFS from the start of cabozantinib was 12.9 months, and median OS was 14.21 months. Most adverse events to treatment (5/6) were low grade. Two (29%) patients were alive at the date of the last follow-up. Conclusion: Cabozantinib is an effective and reasonably well-tolerated treatment option for patients with PDTC. Prospective studies are needed to further investigate the role of cabozantinib in the treatment of PDTC, alone and in combination with other agents, including checkpoint inhibitors.

Abstract Objective Lower socioeconomic status (SES) is a risk factor for poorer pain-related outcomes. Further, the neighborhood environments of disadvantaged communities can create a milieu of increased stress and deprivation that adversely affects pain-related and other health outcomes. Socioenvironmental variables such as the Area Deprivation Index, which ranks neighborhoods based on socioeconomic factors could be used to capture environmental aspects associated with poor pain outcomes. However, it is unclear whether the ADI could be used as a risk assessment tool in addition to individual-level SES. Methods The current study investigated whether neighborhood-level disadvantage impacts knee pain-related outcomes above sociodemographic measures. Participants were 188 community-dwelling adults who self-identified as non-Hispanic Black or non-Hispanic White and reported knee pain. Area Deprivation Index (ADI; measure of neighborhood-level disadvantage) state deciles were derived for each participant. Participants reported educational attainment and annual household income as measures of SES, and completed several measures of pain and function: Short-form McGill Pain Questionnaire, Western Ontario and McMaster Universities Osteoarthritis Index, and Graded Chronic Pain Scale were completed, and movement-evoked pain was assessed following the Short Physical Performance Battery. Hierarchical linear regression analyses were used to assess whether environmental and sociodemographic measures (i.e., ADI 80/20 [80% least disadvantaged and 20% most disadvantaged]; education/income, race) were associated with pain-related clinical outcomes. Results Living in the most deprived neighborhood was associated with poorer clinical knee pain-related outcomes compared to living in less deprived neighborhoods (ps

Abstract. Introduction:. Chronic overlapping pain conditions (COPCs), such as chronic low back pain (cLBP) and fibromyalgia, frequently cooccur and incur substantial healthcare costs. However, to date, much focus has been placed on individual anatomically based chronic pain conditions, whereas little is known about the mechanisms underlying progression to multiple (more than 1) COPCs. This study aims to address the gap by investigating the role of common and modifiable risk factors, specifically sleep and circadian rhythm disturbances, in the development of multiple COPCs. Methods:. The study will enroll 300 participants with cLBP, including 200 with cLBP only and 100 with cLBP plus other COPCs (ie, fibromyalgia, temporomandibular disorders, irritable bowel syndrome, and chronic headaches) and follow them up for 12 months. Sleep and circadian rhythms will be assessed using wireless sleep electroencephalography, 24-hour evaluation of the rhythm of urinary 6-sulfatoxymelatonin, actigraphy, and sleep diaries. Pain amplification using quantitative sensory testing, psychological distress using validated self-report measures, and the number of pain sites using a pain body map will also be assessed. Perspectives:. This research aims to (1) comprehensively characterize sleep/circadian disturbances in individuals with single and multiple COPCs using multimodal in-home assessments; (2) examine the associations between sleep/circadian disturbances, changes in pain amplification, and psychological distress; and (3) investigate the relationship among these factors and the progression in the number of pain sites, a proxy for multiple COPCs. The findings will provide insights into the mechanisms leading to multiple COPCs, potentially informing treatment and prevention strategies for these complex conditions.

In this qualitative study, preservice early childhood education teachers created block-based code to control robots and used the robots in field experience at local preschools. The study is grounded in a conceptual framework that weaves together playful programing and resilience, interlocking concepts that can explain sustained engagement during times of challenge. We investigated how and why preservice early childhood teachers exhibit resilience during collaborative programing. We analyzed their debugging processes, reflections, and interviews using a phenomenological lens. We conducted open and axial coding and analysis of discourse and actions during debugging episodes. Results suggest that teachers exhibited resilience due to the following three reasons: through playful coding, preservice early childhood teachers (a) learned that computer science is approachable and fun, (b) engaged in adaptive attribution, and (c) engaged in joint celebration when they observed each other’s successes during collaborative tinkering. These findings provide potential insights for teacher learning of computing but also for novices learning to program.

Abstract Chronic musculoskeletal pain including knee osteoarthritis (OA) is a leading cause of disability worldwide. Previous research indicates ethnic-race groups differ in the pain and functional limitations experienced with knee OA. However, when socioenvironmental factors are included in analyses, group differences in pain and function wane. Pain-related brain structures are another area where ethnic-race group differences have been observed. Environmental and sociocultural factors e.g., income, education, experiences of discrimination, and social support influence brain structures. We investigate if environmental and sociocultural factors reduce previously observed ethnic-race group differences in pain-related brain structures. Data were analyzed from 147 self-identified non-Hispanic black (NHB) and non-Hispanic white (NHW), middle and older aged adults with knee pain in the past month. Information collected included health and pain history, environmental and sociocultural resources, and brain imaging. The NHB adults were younger and reported lower income and education compared to their NHW peers. In hierarchical multiple regression models, sociocultural and environmental factors explained 6–37% of the variance in pain-related brain regions. Self-identified ethnicity-race provided an additional 4–13% of explanatory value in the amygdala, hippocampus, insula, bilateral primary somatosensory cortex, and thalamus. In the rostral/caudal anterior cingulate and dorsolateral prefrontal cortex, self-identified ethnicity-race was not a predictor after accounting for environmental, sociocultural, and demographic factors. Findings help to disentangle and identify some of the factors contributing to ethnic-race group disparities in pain-related brain structures. Numerous arrays of environmental and sociocultural factors remain to be investigated. Further, the differing sociodemographic representation of our NHB and NHW participants highlights the role for intersectional considerations in future research.

Abstract Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6‐guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT‐PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of CYP2D6 testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6‐impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6 months) genotyping of CYP2D6 with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6‐guided trial recommendations. The primary study outcome is the 3‐month absolute change in the composite pain intensity score assessed using Patient‐Reported Outcomes Measurement Information System (PROMIS) measures. Follow‐up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment.

Introduction: Patients with oligometastatic NSCLC benefit from locally ablative therapies (LAT); the role of adjuvant systemic therapies, however, remains less clear. In a single-arm, phase II clinical trial, we found that patients with oligometastatic NSCLC treated with a year of pembrolizumab after LAT had superior progression-free survival (PFS) compared with a historical control cohort. Herein, we present long-term follow-up on PFS and overall survival (OS). Methods: From February 1, 2015, to September 30, 2017, 45 patients with synchronous or metachronous oligometastatic (≤4 metastatic sites) NSCLC treated with LAT to all sites received adjuvant pembrolizumab every 21 days for up to 16 cycles. The primary efficacy end point was PFS from the start of pembrolizumab. Secondary end points included OS and safety. Median duration of follow-up was 66 months, and data cutoff was December 1, 2022. Results: A total of 45 patients were enrolled and treated with pembrolizumab after LAT (median age, 64 y [range, 46–82]; 21 women [47%]; 31 with a solitary oligometastatic site [69%]). At the data cutoff, 32 patients had progressive disease, 19 patients had died, and 13 patients had no evidence of relapse. Median PFS was 19.7 months (95% confidence interval: 7.6–31.7 mo); median OS was not reached (95% confidence interval: 37.7 mo–not reached). OS at 5 years was 60.0% (SE, 7.4%). Metachronous oligometastatic disease was associated with improved OS and PFS through Cox proportional hazard models. Conclusions: Pembrolizumab after LAT for oligometastatic NSCLC results in promising PFS and OS with a tolerable safety profile.

Mutations in the DYSF gene, encoding the protein dysferlin, lead to several forms of muscular dystrophy. In healthy skeletal muscle, dysferlin concentrates in the transverse tubules and is involved in repairing the sarcolemma and stabilizing Ca2+ signaling after membrane disruption. The DYSF gene encodes 7–8 C2 domains, several Fer and Dysf domains, and a C-terminal transmembrane sequence. Because its coding sequence is too large to package in adeno-associated virus, the full-length sequence is not amenable to current gene delivery methods. Thus, we have examined smaller versions of dysferlin, termed “nanodysferlins,” designed to eliminate several C2 domains, specifically C2 domains D, E, and F; B, D, and E; and B, D, E, and F. We also generated a variant by replacing eight amino acids in C2G in the nanodysferlin missing domains D through F. We electroporated dysferlin-null A/J mouse myofibers with Venus fusion constructs of these variants, or as untagged nanodysferlins together with GFP, to mark transfected fibers We found that, although these nanodysferlins failed to concentrate in transverse tubules, three of them supported membrane repair after laser wounding while all four bound the membrane repair protein, TRIM72/MG53, similar to WT dysferlin. By contrast, they failed to suppress Ca2+ waves after myofibers were injured by mild hypoosmotic shock. Our results suggest that the internal C2 domains of dysferlin are required for normal t-tubule localization and Ca2+ signaling and that membrane repair does not require these C2 domains.

Abstract. Introduction:. Movement-evoked pain (MEP) impacts a substantial proportion of US adults living with chronic pain. Evidence suggests that MEP is influenced by numerous biopsychosocial factors and mediated by mechanisms differing from those of spontaneous pain. However, both characteristic and mechanistic knowledge of MEP remain limited, hindering effective diagnosis and treatment. Objectives:. We asked (1) can chronic pain, functional, psychosocial, and behavioral measures be grouped into descriptive domains that characterize MEP? and (2) what relationships exist between biopsychosocial factors across multiple domains of MEP? Methods:. We formed 6 characteristic domains from 46 MEP-related variables in a secondary analysis of data from 178 individuals (aged 45–85 years) with knee pain. Ratings of pain during 3 functional activities (ie, Balance, Walking, Chair Stand) were used as primary MEP variables. Pearson correlations were calculated to show linear relationships between all individual domain variables. Relationships between variables were further investigated through weighted correlation network analysis. Results:. We observed a unique combination of pain characteristics associated with MEP apart from general pain. Notably, minutes doing physical activity were inversely associated with multiple variables within 4 of the 6 domains. Weighted correlation network analysis largely supported our classification of MEP domains. Additional interdomain relationships were observed, with the strongest existing between MEP, Mechanical Pain, and Multiple Pain Characteristics and Symptoms. Additional relationships were observed both within and between other domains of the network. Conclusion:. Our analyses bolster fundamental understanding of MEP by identifying relevant mechanistic domains and elucidating biopsychosocial and interdomain relationships.

Repetition and structure have a significant place in music theory, but the structure hierarchy and its influences are often ignored in both music analysis and music generation. In this article, we first describe novel algorithms based on repetition to extract music structure hierarchy from a MIDI data set of popular music and show its effectiveness through evaluation. Then, we introduce new data-driven approaches to estimate and validate structural influences in music. Results show that the automatically detected hierarchical repetition structures reveal significant interactions between structure and harmony, melody, rhythm, and predictivity. Different levels of hierarchy interact differently, providing evidence that structural hierarchy plays an important role in our popular music data set beyond simple notions of repetition or similarity. We further study how musical structure has evolved over decades of popular music writing. Finally, we discuss the importance of this work in highlighting roles that structure can play in music analysis, music similarity, music generation, music evaluation, and other music information retrieval tasks.

Pork carcasses and meat may harbor Salmonella and may contaminate other products during harvest and fabrication. Sources of contamination include manure on hides, environmental contamination, ingredients from external sources, and lymph nodes. Swine lymph nodes are often incorporated into ground meat, as their anatomical location makes removal labor prohibitive. A sausage processing plant in the midwestern United States was sampled monthly (except for December) from May 2021 to April 2022 to enumerate Salmonella and Enterobacteriaceae (EB) throughout the sausage manufacturing process to determine high-risk stages and efficiency of existing in-plant interventions. Salmonella serotypes and antimicrobial susceptibility were evaluated on a subset of isolates recovered at the end phases of sausage production. In each collection, samples were taken from the carcasses of eight sows through 11 stages of sausage manufacturing. A total of 830 samples were cultured. Thirty-four Salmonella were isolated from the final three production stages; of these, there were eleven serotypes. Three isolates displayed resistance to ampicillin, whereas the remainder of the isolates were pan-susceptible to the antimicrobials tested. Salmonella and EB were significantly reduced (p < 0.001) by acid washes at different stages of production, and the results point to the beneficial effects of interventions to lessen Salmonella concentrations in retail products.

Considering that certain catabolic products of anaerobic chlorophyll degradation inhibit efflux pump activity, this study was conducted to test if feeding pigs a water-soluble chlorophyllin product could affect the antibiotic resistance profiles of select wild-type populations of fecal bacteria. Trial 1 evaluated the effects of chlorophyllin supplementation (300 mg/meal) on fecal E. coli and enterococcal populations in pigs fed twice daily diets supplemented without or with ASP 250 (containing chlortetracycline, sulfamethazine and penicillin at 100, 100 and 50 g/ton, respectively). Trial 2, conducted similarly, evaluated chlorophyllin supplementation in pigs fed diets supplemented with or without 100 g tylosin/ton. Each trial lasted 12 days, and fecal samples were collected and selectively cultured at 4-day intervals to enumerate the total numbers of E. coli and enterococci as well as populations of these bacteria phenotypically capable of growing in the presence of the fed antibiotics. Performance results from both studies revealed no adverse effect (p > 0.05) of chlorophyllin, antibiotic or their combined supplementation on average daily feed intake or average daily gain, although the daily fed intake tended to be lower (p = 0.053) for pigs fed diets supplemented with tylosin than those fed diets without tylosin. The results from trial 1 showed that the ASP 250-medicated diets, whether without or with chlorophyllin supplementation, supported higher (p < 0.05) fecal E. coli populations than the non-medicated diets. Enterococcal populations, however, were lower, albeit marginally and not necessarily significantly, in feces from pigs fed the ASP 250-medicated diet than those fed the non-medicated diet. Results from trial 2 likewise revealed an increase (p < 0.05) in E. coli and, to a lesser extent, enterococcal populations in feces collected from pigs fed the tylosin-medicated diet compared with those fed the non-medicated diet. Evidence indicated that the E. coli and enterococcal populations in trial 1 were generally insensitive to penicillin or chlortetracycline, as there were no differences between populations recovered without or with antibiotic selection. Conversely, a treatment x day of treatment interaction observed in trial 2 (p < 0.05) provided evidence, albeit slight, of an enrichment of tylosin-insensitive enterococci in feces from the pigs fed the tylosin-medicated but not the non-medicated diet. Under the conditions of the present study, it is unlikely that chlorophyllin-derived efflux pump inhibitors potentially present in the chlorophyllin-fed pigs were able to enhance the efficacy of the available antibiotics. However, further research specifically designed to optimize chlorophyll administration could potentially lead to practical applications for the swine industry.

Introduction: Substantial barriers to screening exist for medically underserved populations, especially adults with limited English proficiency (LEP). We examined the proportion of US adults aged 45–75 up-to-date with colorectal cancer (CRC) screening by LEP after 2018. The American Cancer Society began recommending CRC screening for adults 45–49 in 2018. Methods: We analyzed cross-sectional data of adults 45–75 years old participating in the 2019 or 2021 National Health Interview Survey (N = 25,611). Adults were considered up-to-date with screening if they reported any stool test within 1 year, stool-DNA testing within 3 years, or colonoscopy within 10 years. Adults who interviewed in a language other than English were considered to have LEP. Adults not up-to-date with screening were asked if a healthcare professional (HCP) recommended screening, and if so which test(s). Regression models conducted in 2022–2023 evaluated receipt of screening, adjusting for sociodemographics, year, and healthcare access. Results: Overall, 54.0 % (95 % CI 53.1–54.9 %) of participants were up-to-date with screening (9.4 % aged 45–49 vs 75.5 % aged 65–75); prevalence increased from 2019 (52.9 %) to 2021(55.2 %). Adults with LEP (vs English proficiency) were less likely to be up-to-date with screening (31.6 % vs. 56.8 %, [aPR 0.86 (0.77–0.96)]). Among adults not up-to-date, 15.0 % reported their HCP recommended screening (8.4 % among adults with LEP). Conclusions: Nearly half of US adults were not up-to-date with CRC screening in 2019 and 2021 and few reported being recommended screening. Adults with LEP and those 45–49 were least likely to be screened suggesting targeted interventions are needed for these populations.

Background: The concordance between radiograph-derived Kellgren–Lawrence (KL) scores for knee osteoarthritis (KOA) and experimental and clinical pain and KOA-related physical function is conflicting. Objectives: We investigate whether the inclusion of dispositional traits reduces variability between KOA radiographic findings, experimental pain, clinical pain, and function in individuals with knee pain. Design: This study is a cross-sectional, secondary analysis of data collected from the UPLOAD-II study. Methods: Adults aged 45–85 years with and without knee pain were enrolled. Data collected included sociodemographics, knee radiographs, experimental pain, clinical pain and function, and trait affect. Vulnerable and protective dispositional traits were classified from combined positive and negative trait affect measures. KL scores were determined from the knee radiographs. Unadjusted and adjusted (age, sex, comorbidities, and body mass index) regression analyses were completed with SAS version 9.4 (Cary, NC, USA). Results: The study included 218 individuals with a mean age of 58 years, 63.6% women, and 48.2% non-Hispanic black adults. Dispositional traits were associated with the experimental pain measures. No association between radiographic KOA and experimental pain was observed. In a combined and adjusted analysis, dispositional traits were predictive of knee punctate pain temporal summation ( p = 0.0382). Both dispositional traits and radiographic KOA scores independently and combined were predictive of Graded Chronic Pain Scale pain and function, and Western Ontario and McMaster University pain and function ( p s ⩽ 0.01). Improvements in R 2 were noted across all models with the inclusion of dispositional traits. Conclusion: Consideration of dispositional traits reduces the variability between radiographic KOA and pain and function. Non-pathological and associated pain-related psychological factors, dispositional traits might serve as parsimonious proxy tools to improve clinical assessments. Registration: N/A.

Commentary on: van den Broeke EN, Crombez G, Vlaeyen JWS. Reconceptualizing sensitization in pain: back to basics. PAIN Reports 2024;9:e1125.

Lipoarabinomannan (LAM) is a promising target biomarker for diagnosing subclinical and clinical tuberculosis (TB). Urine LAM (uLAM) testing using rapid diagnostic tests (RDTs) has been approved for people living with HIV (PLWH), however there is limited data regarding uLAM levels in HIV-negative (HIV-ve) adults with clinical TB. We conducted a clinical study of adults presenting with clinical TB-related symptoms at the National Lung Hospital in Hanoi, Vietnam. The uLAM concentrations were measured using electrochemiluminescent (ECL) immunoassays and compared to a microbiological reference standard (MRS) using GeneXpert Ultra and TB culture testing. Estimated uLAM concentrations above plate specific calculated limit of detection (LOD) were considered uLAM positive. Additional microbiological testing was conducted for possible extrapulmonary TB (EPTB). Among 745 participants enrolled, 335 (44.9%) participants with presumptive pulmonary TB (PTB) and 6 (11.3%) participants with presumptive EPTB had confirmed TB disease. Overall, the S/A antibody pair had a sensitivity of 39% (95% Confidence Interval [CI] 0.33, 0.44) and a specificity of 97% (95% CI 0.96, 0.99) compared to the MRS. The F/A antibody pair had a sensitivity of 41% (95% CI 0.35, 0.47) and a specificity of 79% (95% CI 0.75, 0.84). S/A provided greater discriminatory ability compared to F/A for both individuals with presumptive PTB (AUROC: 0.74 vs 0.63, p

We present an overview of results from a magnetofrictional model of the entire solar corona over a period of 47 yr. The simulation self-consistently reproduces decades of solar phenomena, varying in duration between rapid eruptions and the long-term solar cycles, from an input of observed active regions emerging at the photosphere. We have developed a geometric approach to use magnetic helicity to identify and localize the frequent eruptions that occur in the simulation. This method allows us to match our results to extreme-ultraviolet observations of transient events. We have analyzed the evolving magnetic topology by computing the squashing factor and segmenting the corona into discrete magnetic domains bounded by the Separatrix-Web. The simulations show a more dynamic structure to the Separatrix-Web than is predicted by potential field models, which may explain solar wind observations.

Thermal nonequilibrium (TNE) is a condition of the plasma in the solar corona in which the local rate of energy loss due to radiation increases to the point that it cannot be sustained by the various heating terms acting on the plasma, precluding the existence of a steady state. The limit cycles of precipitation and evaporation that result from TNE have been simulated in 1D models of coronal loops, as well as 2D and 3D models of the solar chromosphere and lower corona. However, a careful study of TNE in the solar wind has not been performed until now. Here, we demonstrate that for suitable combinations of local and global heating rates, it is possible for the plasma to exhibit a TNE condition, even in the context of a transonic solar wind with appreciable mass and energy fluxes. This implies limits on the amount of footpoint heating that can be withstood under steady-state conditions in the solar wind, and may help to explain the variability of solar wind streams that emanate from regions of highly concentrated magnetic flux on the solar surface. The implications of this finding pertain to various sources of high-density solar wind, including plumes that form above regions of mixed magnetic polarity in polar coronal holes and the slow solar wind that emanates from coronal hole boundaries.

We present a new code for the tracing of magnetic field lines and calculation of related quantities such as the squashing factor in the solar corona. The Universal Fieldline Tracer ( UFiT ) is an open-source package that can currently take inputs directly from four well-established coronal models, with additional models planned to be made directly accessible in the future. This package contains tools to make use of large-scale three-dimensional field line maps to calculate volumetric quantities, such as the total volume of the open corona, or the fraction that maps to regions on the solar surface within some distance of a coronal hole boundary, which may be relevant to phenomenological models of solar wind speed such as the Wang–Sheeley–Arge model. Synthetic coronagraphs can also be produced rapidly by this package. We have postprocessed long-term magnetofrictional simulations to demonstrate that the separatrix web occupies a larger fraction of the corona during solar maximum than solar minimum.

An expansion of the cross-sectional area directly impacts the mass flow along a coronal loop and significantly alters the radiative and hydrodynamic evolution of that loop as a result. Previous studies have found that an area expansion from the chromosphere to the corona significantly lengthens the cooling time of the corona and appears to suppress draining from the corona. In this work, we examine the fluid dynamics to understand how the mass flow rate, the energy balance, and the cooling and draining timescales are affected by a nonuniform area. We find that in loops with moderate or large expansion (cross-sectional area expansion factors of 2, 3, 10, 30, 100 from the photosphere to the apex), impulsive heating, for either direct thermal heating or electron beam heating, induces a steady flow into the corona, so that the coronal density continues to rise during the cooling phase, whereas a uniform loop drains during the cooling phase. The induced upflow carries energy into the corona, balancing the losses from thermal conduction, and continues until thermal conduction weakens enough so that it can no longer support the radiative losses of the transition region. As a result, the plasma cools primarily radiatively until the onset of catastrophic collapse. The speed and duration of the induced upflow both increase in proportion to the rate of area expansion. We argue that observations of blueshifted spectral lines, therefore, could place a constraint on a loop’s area expansion.

BACKGROUND: Phthalates and their replacements have been implicated as developmental toxicants. Young children may be exposed to phthalates/replacements when using skin care products (SCPs). OBJECTIVES: Our objective is to assess the associations between use of SCPs and children&apos;s urinary phthalate/replacement metabolite concentrations. METHODS: Children (4--8 years old) from the Environmental Influences on Child Health Outcomes-Fetal Growth Study (ECHO-FGS) cohort provided spot urine samples from 2017 to 2019, and mothers were queried about children&apos;s SCP use in the past 24 h (n = 906). Concentrations of 16 urinary phthalate/replacement metabolites were determined by liquid chromatography-tandem mass spectrometry (n = 630). We used linear regression to estimate the child&apos;s use of different SCPs as individual predictors of urinary phthalate/replacement metabolites, adjusted for urinary specific gravity, age, sex assigned at birth, body mass index, and self-reported race/ethnic identity, as well as maternal education, and season of specimen collection. We created self-organizing maps (SOM) to group children into "exposure profiles" that reflect discovered patterns of use for multiple SCPs. RESULTS: Children had lotions applied (43.0%) frequently, but "2-in-1" hair-care products (7.5%), sunscreens (5.9%), and oils (4.3%) infrequently. Use of lotions was associated with 1.17-fold [95% confidence interval (CI): 1.00, 1.34] greater mono-benzyl phthalate and oils with 2.86-fold (95% CI: 1.89, 4.31) greater monoethyl phthalate (MEP), 1.43-fold (95% CI: 1.09, 1.90) greater monobutyl phthalate (MBP), and 1.40-fold (95% CI: 1.22, 1.61) greater low-molecular-weight phthalates (LMW). Use of 2-in-1 haircare products was associated with 0.84-fold (95% CI: 0.72, 0.97) and 0.78-fold (95% CI: 0.62, 0.98) lesser mono(3-carboxypropyl) phthalate (MCPP) and MBP, respectively. Child&apos;s race/ethnic identity modified the associations of lotions with LMW, oils with MEP and LMW, sunscreen with MCPP, ointments with MEP, and hair conditioner with MCPP. SOM identified four distinct SCP-use exposure scenarios (i.e., profiles) within our population that predicted 1.09-fold (95% CI: 1.03, 1.15) greater mono-carboxy isononyl phthalate, 1.31-fold (95% CI: 0.98, 1.77) greater mono-2-ethyl-5-hydroxyhexyl terephthalate, 1.13-fold (95% CI: 0.99, 1.29) greater monoethylhexyl phthalate, and 1.04-fold (95% CI: 1.00, 1.09) greater diethylhexyl phthalate. DISCUSSION: We found that reported SCP use was associated with urinary phthalate/replacement metabolites in young children. These results may inform policymakers, clinicians, and parents to help limit children&apos;s exposure to developmental toxicants. https://doi.org/10.1289/EHP13937, Introduction Phthalates are endocrine-disrupting chemicals, (1) and children's exposure has been associated with differences in body composition, (2) neurodevelopment, (2-4) and pulmonary and immune function. (5,6) Children are exposedto phthalates [...]