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OBJECTIVE: To evaluate the diagnostic performance and image quality of accelerated Turbo Spin Echo sequences using deep-learning (DL) reconstructions compared to conventional sequences in knee and ankle MRIs of children and young adults. MATERIALS AND METHODS: IRB-approved prospective study consisting of 49 MRIs from 48 subjects (10 males, mean age 16.4 years, range 7-29 years), with each MRI consisting of both conventional and DL sequences. Sequences were evaluated blindly to determine predictive values, sensitivity, and specificity of DL sequences using conventional sequences and knee arthroscopy (if available) as references. Physeal patency and appearance were evaluated. Qualitative parameters were compared. Presence of undesired image alterations was assessed. RESULTS: The prevalence of abnormal findings in the knees and ankles were 11.7% (75/640), and 11.5% (19/165), respectively. Using conventional sequences as reference, sensitivity and specificity of DL sequences in knees were 90.7% and 99.3%, and in ankles were 100.0% and 100.0%. Using arthroscopy as reference, sensitivity and specificity of DL sequences were 80.0% and 95.8%, and of conventional sequences were 80.0% and 97.9%. Agreement of physeal status was 100.0%. DL sequences were qualitatively "same-or-better" compared to conventional (p < 0.032), except for pixelation artifact for the PDFS sequence (p = 0.233). No discrete image alteration was identified in the knee DL sequences. In the ankle, we identified one DL artifact involving a tendon (0.8%, 1/125). DL sequences were faster than conventional sequences by a factor of 2 (p < 0.001). CONCLUSION: In knee and ankle MRIs, DL sequences provided similar diagnostic performance and "same-or-better" image quality than conventional sequences at half the acquisition time.
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Purpose of Review: Hypertension (HTN) and obesity are increasing in prevalence and severity in adolescents and have significant implications for long term morbidity and mortality. This review focuses on the diagnosis and management of HTN in adolescents with obesity with an emphasis on co-management of the two conditions. Recent Findings: Recent studies affirm the increasing prevalence of abnormal blood pressures and diagnoses of HTN associated with increased adiposity. Current guidelines recommend routine screening with proper technique for HTN in patients with obesity. Additionally, obesity and HTN related co-occurring medical conditions should be evaluated as there is frequently a bidirectional impact on risk and outcomes. Importantly, advances in adolescent obesity management have subsequently led to positive implications for the management of obesity-related comorbidities such as HTN. The co-management of obesity and HTN is an emerging strategy for treatment and prevention of additional morbidity and mortality as patients progress to adulthood. Summary: In adolescent patients with obesity, prompt recognition and appropriate diagnosis of HTN as well as related co-occurring conditions are necessary first steps in management. Co-management of obesity and HTN is likely to lead to improved outcomes. While lifestyle interventions serve as the foundation to this management, adjunctive and emerging therapies should be considered to adequately treat both conditions.
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SIGNIFICANCE: Cigars are sometimes marketed with cannabis references because they are often used for smoking blunts (i.e., cannabis rolled in cigar paper with or without tobacco). However, little research exists on the impact of cannabis co-marketing on cigar perceptions. METHODS: Participants included 506 US youth (ages 15-20) recruited April-June 2023 through Qualtrics who reported ever using little cigars or cigarillos (LCCs), past 30-day use of LCCs, or susceptibility to using LCCs. We then conducted a between-subjects experiment, randomizing youth to view one of two cigarillo packages: 1) a package with cannabis co-marketing (i.e., the package included a cannabis-related flavor descriptor and the word "blunt" appeared in the brand name and product label) or 2) a package with no cannabis co-marketing. We assessed the effects of the packaging on perceptions of product ingredients, addictiveness and harm perceptions, product appeal, susceptibility to using the product shown, and purchase intentions. RESULTS: Packages with cannabis co-marketing were perceived as more likely to contain cannabis (OR: 5.56, 95 % CI: 3.73, 8.27) and less likely to contain tobacco (OR: 0.42, 95 % CI: 0.25, 0.70) or nicotine (OR: 0.57, 95 % CI: 0.40, 0.82). Cannabis co-marketing also led to higher susceptibility to using the product shown (B: 0.21, p = 0.02). We did not find evidence that cannabis co-marketing changed harm perceptions or purchase intentions. CONCLUSIONS: Among a sample of US youth, cannabis co-marketing on cigar packages may change perceptions of product ingredients and increase susceptibility to using such products, which could lead to the initiation of cigars and cannabis.
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OBJECTIVE: We examined length of postpartum hospitalization for live births during the COVID-19 pandemic and explored how pandemic circumstances influenced postpartum hospital experiences. METHODS: We conducted a cross-provincial, convergent parallel mixed-methods study in Ontario (ON) and British Columbia (BC), Canada. We included birthing persons (BPs) with an in-hospital birth in ON from 1 January to 31 March 2019, 2021, and 2022 (quantitative), and BPs (≥18 years) in ON or BC from 1 May 2020 to 1 December 2021 (qualitative). We linked multiple health administrative datasets at ICES and developed multivariable linear regression models to examine length of hospital stay (quantitative). We conducted semi-structured interviews using qualitative descriptive to understand experiences of postpartum hospitalization (qualitative). Data integration occurred during design and interpretation. RESULTS: Relative to 2019, postpartum hospital stays decreased significantly by 3.29 hours (95% CI: -3.58 to -2.99; 9.2% reduction) in 2021 and 3.89 hours (95% CI: -4.17 to -3.60; 9.0% reduction) in 2022. After adjustment, factors associated with shortened stays included: giving birth during COVID-19, social deprivation (more ethnocultural diversity), midwifery care, multiparity, and lower newborn birth weight. Postpartum hospital experiences were impacted by risk perception of COVID-19 infection, clinical care and hospital services/amenities, visitor policies, and duration of stay. CONCLUSION: Length of postpartum hospital stays decreased during COVID-19, and qualitative findings described unmet needs for postpartum services. The integration of large administrative and interview data expanded our understanding of observed differences. Future research should investigate the impacts of shortened stays on health services outcomes and personal experiences. OBJECTIF: Nous avons examiné la durée d'hospitalisation post-partum pour les cas de naissance vivante pendant la pandémie de COVID-19 et exploré comment les circonstances de la pandémie ont influencé l'expérience post-partum à l'hôpital. MéTHODES: Nous avons mené une étude interprovinciale selon un modèle mixte parallèle et convergent en Ontario (Ont.) et en Colombie-Britannique (C.-B.), au Canada. Nous avons inclus les personnes ayant accouché à l'hôpital en Ont. entre le 1 janvier et le 31 mars 2019, 2021 et 2022 (quantitatif), et celles ayant accouché (≥ 18 ans) entre le 1 mai 2020 et le 1 décembre 2021 en Ont. ou en C.-B. (qualitatif). Nous avons relié plusieurs ensembles de données de santé administratives à l'ICES et développé des modèles de régression linéaire multivariable pour examiner la durée d'hospitalisation (quantitative). Nous avons mené des entretiens semi-structurés en utilisant une méthode qualitative descriptive pour comprendre les expériences d'hospitalisation post-partum (qualitative). L'intégration des données a eu lieu pendant la conception de l'étude et l'interprétation. RéSULTATS: Par rapport à 2019, la durée de l'hospitalisation post-partum a significativement diminué de 3,29 heures (IC à 95 % : -3,58 à -2,99; réduction de 9,2 %) en 2021 et de 3,89 heures (IC à 95 % : -4,17 à -3,60; réduction de 9,0 %) en 2022. Après ajustement, les facteurs associés à la réduction de la durée d'hospitalisation étaient les suivants : accouchement pendant la pandémie de COVID-19, manque de socialisation (plus grande diversité ethnoculturelle), prise en charge en pratique sage-femme, multiparité et poids plus faible du nouveau-né à la naissance. L'expérience d'hospitalisation post-partum était influencée par la perception du risque de contracter la COVID-19, les soins cliniques et les services et commodités à l'hôpital, les politiques relatives aux visiteurs et la durée de l'hospitalisation. CONCLUSION: La durée d'hospitalisation post-partum a diminué pendant la pandémie de COVID-19, et les résultats qualitatifs ont décrit des besoins non satisfaits en matière de services post-partum. L'intégration de grands ensembles de données administratives et d'entretiens a permis de mieux comprendre les différences observées. Les recherches futures devront se pencher sur l'impact de la réduction de la durée d'hospitalisation sur les résultats des services de santé et les expériences personnelles.
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BACKGROUND: Older adults with severe aortic stenosis (AS) may receive care in a nursing home (NH) prior to undergoing transcatheter aortic valve replacement (TAVR). NH level of care can be used to stabilize medical conditions, to provide rehabilitation services, or for long-term care services. Our primary objective is to determine whether NH utilization pre-TAVR can be used to stratify patients at risk for higher mortality and poor disposition outcomes at 30 and 365 days post-TAVR. METHODS: We conducted a retrospective cohort study among Medicare beneficiaries who spent ≥1 day in an NH 6 months before TAVR (2011-2019). The intensity of NH utilization was categorized as low users (1-30 days), medium users (31-89 days), long-stay NH residents (≥ 100 days, with no more than a 10-day gap in care), and high post-acute rehabilitation patients (≥90 days, with more than a 10-day gap in care). The probabilities of death and disposition were estimated using multinomial logistic regression, adjusting for age, sex, and race. RESULTS: Among 15,581 patients, 9908 (63.6%) were low users, 4312 (27.7%) were medium users, 663 (4.3%) were high post-acute care rehab users, and 698 (4.4%) were long-stay NH residents before TAVR. High post-acute care rehabilitation patients were more likely to have dementia, weight loss, falls, and extensive dependence of activities of daily living (ADLs) as compared with low NH users. Mortality was the greatest in high post-acute care rehab users: 5.5% at 30 days, and 36.4% at 365 days. In contrast, low NH users had similar mortality rates compared with long-stay NH residents: 4.8% versus 4.8% at 30 days, and 24.9% versus 27.0% at 365 days. CONCLUSION: Frequent bouts of post-acute rehabilitation before TAVR were associated with adverse outcomes, yet this metric may be helpful to determine which patients with severe AS could benefit from palliative and geriatric services.
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This cross-sectional study evaluates the use of oral anticoagulants and antiplatelets, including aspirin, among nursing home residents with atrial fibrillation.
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INTRODUCTION: There is a growing body of literature that shows geographic social vulnerability, which seeks to measure the resiliency of a community to withstand unforeseen disasters, may be associated with negative outcomes after traumatic injury. For motor vehicle collisions (MVCs) specifically, it is unknown how the resources of a patient's home environment may interact with resources of the environment where the crash occurred. METHODS: We merged publicly available crash data from the state of Michigan with the Michigan Trauma Quality Improvement dataset. A social vulnerability index (SVI) score was calculated for each ZIP code and was then cross-referenced between the location of the MVC (Crash-SVI) and the patient's home address (Home-SVI). SVI was divided into quintiles, with higher numbers indicating greater vulnerability. Adjusted logistic regression models using least absolute shrinkage and selection operator for feature selection and regularization were performed sequentially using patient, vehicular, and environmental variables to identify associations between Home-SVI and Crash-SVI, with mortality and injury severity score (ISS) greater than 15 (ISS15). RESULTS: Between January 2020 and December 2022, a total of 14,706 patients were identified. Most MVCs (75.3% of all patients) occurred in the second through fourth quintiles of SVI. In all cases, Crash-SVI occurred most frequently within the same quintile as the patient's Home-SVI. Average crash speed limits showed a significant negative association with increasing SVI. On adjusted logistic regression, there were significantly increased odds of mortality for the fifth quintile of Home-SVI in comparison to the first quintile when adjusted for patient factors; but this lost significance after the addition of vehicular or environmental variables. In contrast, there were decreased odds of ISS15 for the highest quintiles of Crash-SVI in all logistic regression models. CONCLUSIONS: Geographic social vulnerability markers were associated with lower MVC-associated injury severity, perhaps in part because of the association with lower speed limit in these areas.
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Background: Over the past decade, youth e-cigarette use has grown into a national epidemic, with Native Hawaiian and Pacific Islander (NHPI) youths' rates among some of the highest in the nation. Family factors significantly contribute to NHPI youths' decisions to engage in or resist substance use, yet few studies have specifically examined familial influences on NHPI youths' substance use decision-making and behaviors. Objective: The objective of this study is to examine adult familial influences on rural NHPI youths' decisions to engage in e-cigarette use. Method: Seventeen gender-specific focus groups with NHPI youths (N = 69) from eight public schools on Hawai'i Island were conducted. Results: Two family-related themes emerged from the data: 1) parental substance use permissiveness, and 2) family normalization of e-cigarette use. Conclusions: Examining adult familial contributors to NHPI youths' e-cigarette use needs to be part of a comprehensive effort to address NHPI health and substance use disparities. Prevention interventions should be explicit in addressing the family and relational context of NHPI youths' substance use.
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"Cases of SCMR" is a case series on the SCMR website (https://www.scmr.org) for the purpose of education. The cases reflect the clinical presentation, and the use of cardiovascular magnetic resonance (CMR) in the diagnosis and management of cardiovascular disease. The 2023 digital collection of cases are presented in this manuscript.
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PURPOSE: The aim of this study is to identify likely pathogenic (LP) and pathogenic (P) genetic results for autism that can be returned to participants in SPARK (SPARKforAutism.org): a large recontactable cohort of people with autism in the United States. We also describe the process to return these clinically confirmed genetic findings. METHODS: We present results from microarray genotyping and exome sequencing (ES) of 21,532 individuals with autism and 17,785 of their parents. We returned LP and P (American College of Medical genetics (ACMG) criteria) copy number variants (CNVs), chromosomal aneuploidies, and variants in genes with strong evidence of association with autism and intellectual disability. RESULTS: We identified 1903 'returnable' LP/P variants in 1861 individuals with autism (8.6%). 89.5% of these variants were not known to participants. The diagnostic genetic result was returned to 589 participants (53% of those contacted). Features associated with a higher probability of having a returnable result include cognitive and medically complex features, being female, being White (versus non-White) and being diagnosed more than 20 years ago. We also find results among autistics across the spectrum, as well as in transmitting parents with neuropsychiatric features but no autism diagnosis. CONCLUSION: SPARK offers an opportunity to assess returnable results among autistic people who have not been ascertained clinically. SPARK also provides practical experience returning genetic results for a behavioral condition at a large scale.
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OBJECTIVE: To determine the impact of prior gestational diabetes mellitus (GDM) on perinatal outcomes in a subsequent GDM pregnancy. METHODS: This retrospective cohort study included 544 multiparous patients with two consecutive pregnancies between 2012-2019, where the second (index) pregnancy was affected by GDM. The primary exposure was prior GDM diagnosis, categorized into medical and dietary management. The primary outcome was a composite including need for pharmacotherapy, large-for-gestational age, or neonatal hypoglycemia. Adjusted odds ratios (aOR) were calculated using multivariable logistic regression controlling for maternal age, pre-pregnancy body mass index, and gestational age at GDM diagnosis in the index pregnancy. RESULTS: Of the 544 patients, 164 (30.1%) had prior GDM. Prior GDM significantly increased the likelihood of composite outcome compared to no prior GDM (74.4% vs. 57.4%; P < 0.001). After adjusting for confounders, prior GDM remained significantly associated with the composite outcome (aOR 2.03, 95% confidence interval [CI] 1.31-3.15). Stratifying by prior GDM treatment modality, a significant association was found for prior pharmacotherapy-controlled GDM (aOR 3.29, 95% CI 1.64-6.59), but not for prior diet-controlled GDM (aOR = 1.54, 95% CI 0.92-2.60). CONCLUSION: A history of pharmacotherapy-controlled GDM in a previous pregnancy increases odds of adverse perinatal outcomes in a subsequent GDM pregnancy.
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Season length and its associated variables can influence the expression of social behaviors, including the occurrence of eusociality in insects. Eusociality can vary widely across environmental gradients, both within and between different species. Numerous theoretical models have been developed to examine the life history traits that underlie the emergence and maintenance of eusociality, yet the impact of seasonality on this process is largely uncharacterized. Here, we present a theoretical model that incorporates season length and offspring development time into a single, individual-focused model to examine how these factors can shape the costs and benefits of social living. We find that longer season lengths and faster brood development times are sufficient to favor the emergence and maintenance of a social strategy, while shorter seasons favor a solitary one. We also identify a range of season lengths where social and solitary strategies can coexist. Moreover, our theoretical predictions are well-matched to the natural history and behavior of two flexibly-eusocial bee species, suggesting our model can make realistic predictions about the evolution of different social strategies. Broadly, this work reveals the crucial role that environmental conditions can have in shaping social behavior and its evolution and underscores the need for further models that explicitly incorporate such variation to study evolutionary trajectories of eusociality.
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In preclinical Alzheimer's disease (AD), spatial learning and memory is impaired. We reported similar impairments in 3xTg-AD mice on a virtual maze (VM) spatial-reorientation-task that requires using landmarks to navigate. Hippocampal (HPC)-cortical dysfunction during sleep (important for memory consolidation) is a potential mechanism for memory impairments in AD. We previously found deficits in HPC-cortical coordination during sleep coinciding with VM impairments the next day. Some forms of 40 Hz stimulation seem to clear AD pathology in mice, and improve functional connectivity in AD patients. Thus, we implanted a recording array targeting parietal cortex (PC) and HPC to assess HPC-PC coordination, and an optical fiber targeting HPC for 40 Hz or sham optogenetic stimulation in 3xTg/PV cre mice. We assessed PC delta waves (DW) and HPC sharp wave ripples (SWRs). In sham mice, SWR-DW cross-correlations were reduced, similar to 3xTg-AD mice. In 40 Hz mice, this phase-locking was rescued, as was performance on the VM. However, rescued HPC-PC coupling no longer predicted performance as in NonTg animals. Instead, DWs and SWRs independently predicted performance in 40 Hz mice. Thus, 40 Hz stimulation of HPC rescued functional interactions in the HPC-PC network, and rescued impairments in spatial navigation, but did not rescue the correlation between HPC-PC coordination during sleep and learning and memory. Together this pattern of results could inform AD treatment timing by suggesting that despite applying 40 Hz stimulation before significant tau and amyloid aggregation, pathophysiological processes led to brain changes that were not fully reversed even though cognition was recovered. Significance Statement: One of the earliest symptoms of Alzheimer's disease (AD) is getting lost in space or experiencing deficits in spatial navigation, which involve navigation computations as well as learning and memory. We investigated cross brain region interactions supporting memory formation as a potential causative factor of impaired spatial learning and memory in AD. To assess this relationship between AD pathophysiology, brain changes, and behavioral alterations, we used a targeted approach for clearing amyloid beta and tau to rescue functional interactions in the brain. This research strongly connects brain activity patterns during sleep to tau and amyloid accumulation, and will aid in understanding the mechanisms underlying cognitive dysfunction in AD. Furthermore, the results offer insight for improving early identification and treatment strategies.
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The purpose of this manuscript is to describe the protocol for an Alzheimer's Association-funded cluster randomized trial that focuses on engaging assisted living residents with dementia in meaningful activity to help address their behavioral symptoms of distress using a theoretically based approach, Meaningful Activity for Managing Behavioral Symptoms of Distress (MAC-4-BSD). The development of MAC-4-BSD was based on the Social Ecological Model and Social Cognitive Theory. The MAC-4-BSD intervention includes the following four steps: (1) Assessment of the assisted living physical environment and policies to facilitate meaningful activity; (2) Education of staff about implementation of meaningful activity; (3) Assessment of resident preferences and goals for meaningful activity; (4) Mentoring and motivating staff and residents to facilitate engagement in meaningful activity. The overall aim of this study will be to determine the feasibility and preliminary efficacy of implementing the MAC-4-BSD intervention and test whether it will improve residents' engagement in meaningful activity, behavioral symptoms of distress, and quality of life as well as the environment and policies to promote meaningful activity in assisted living.
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PURPOSE: [177Lu]Lu-DOTATATE is an established somatostatin receptor (SSTR) agonist for the treatment of metastasized neuroendocrine neoplasms, while the SSTR antagonist [177Lu]Lu-DOTA-LM3 has only scarcely been employed in clinics. Impressive preclinical data obtained with [161Tb]Tb-DOTA-LM3 in tumor-bearing mice indicated the potential of terbium-161 as an alternative to lutetium-177. The aim of the present study was to compare the tolerability of 161Tb- and 177Lu-based DOTA-LM3 and DOTATATE in immunocompetent mice. METHODS: Dosimetry calculations were performed based on biodistribution data of the radiopeptides in immunocompetent mice. Treatment-related effects on blood cell counts were assessed on Days 10, 28 and 56 after application of [161Tb]Tb-DOTA-LM3 or [161Tb]Tb-DOTATATE at 20 MBq per mouse. These radiopeptides were also applied at 100 MBq per mouse and the effects compared to those observed after application of the 177Lu-labeled counterparts. Bone marrow smears, blood plasma parameters and organ histology were assessed at the end of the study. RESULTS: The absorbed organ dose was commonly higher for the SSTR antagonist than for the SSTR agonist and for terbium-161 over lutetium-177. Application of a therapeutic activity level of 20 MBq [161Tb]Tb-DOTA-LM3 or [161Tb]Tb-DOTATATE was well tolerated without major hematological changes. The injection of 100 MBq of the 161Tb- and 177Lu-based somatostatin analogues affected the blood cell counts, however. The lymphocytes were 40-50% lower in treated mice compared to the untreated controls on Day 10 irrespective of the radionuclide employed. At the same timepoint, thrombocyte and erythrocyte counts were 30-50% and 6-12% lower, respectively, after administration of the SSTR antagonist (p < 0.05) while changes were less pronounced in mice injected with the SSTR agonist. All blood cell counts were in the normal range on Day 56. Histological analyses revealed minimal abnormalities in the kidneys, liver and spleen of treated mice. No correlation was observed between the organ dose and frequency of the occurrence of abnormalities. CONCLUSION: Hematologic changes were more pronounced in mice treated with the SSTR antagonist than in those treated with the SSTR agonist. Despite the increased absorbed dose delivered by terbium-161 over lutetium-177, [161Tb]Tb-DOTA-LM3 and [161Tb]Tb-DOTATATE should be safe at activity levels that are recommended for their respective 177Lu-based analogues.
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BACKGROUND: Paroxysmal atrial fibrillation (pAF) occurs sporadically and can impair athletic performance. Gold standard for diagnosis is surface electrocardiography (ECG), however, this requires AF to be sustained. Implantable loop recorders (ILRs) are routinely used for AF detection in human medicine. While ILR placement has been studied in horses, its AF detection performance is unknown. OBJECTIVES: (I) Validation of ILRs for AF detection in horses. (II) Determining pAF incidence using ILRs and estimate the positive predictive value (PPV). STUDY DESIGN: (I) Experimental study; (II) Longitudinal observational study. METHODS: (I) Implantation of ILRs in 15 horses with AF and 13 horses in sinus rhythm. Holter ECGs were recorded at: 1, 4, 8, 12 and 16 weeks of AF. The ILR ECGs were compared with surface ECGs to assess diagnostic sensitivity and specificity. (II) Eighty horses (43 Warmbloods, 37 Standardbreds) with ILRs were monitored for 367 days [IQR 208-621]. RESULTS: (I) ILRs detected AF on all recording days, in horses with AF, with a sensitivity of 66.1% (95% CI: 65.8-66.5) and a specificity of 99.99% (95% CI: 99.97-99.99). The sensitivity remained consistent across all time points. (II) The incidence of pAF was 6.3% (5/80). In horses with pAF, the PPV ranged from 8% to 87%. Increased body condition score (BCS > 6/9) was associated with an increased number of false positive episodes (p = 0.005). MAIN LIMITATIONS: (I) Horses were stabled during the ECG recordings, and AF was induced, rather than naturally occurring pAF. (II) Integrated algorithm in this ILR is optimised for AF detection in humans using remote monitors. Additionally, sensing is affected by motion artefacts. CONCLUSION: The ILR reliably detected AF in resting horses, particularly in horses with normal BCS (6/9). The ILR proved useful to detect pAF and is recommended alongside Holter monitoring for diagnostic workup of horses with suspected pAF.
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Importance: Research on resilience after trauma has often focused on individual-level factors (eg, ability to cope with adversity) and overlooked influential neighborhood-level factors that may help mitigate the development of posttraumatic stress disorder (PTSD). Objective: To investigate whether an interaction between residential greenspace and self-reported individual resources was associated with a resilient PTSD trajectory (ie, low/no symptoms) and to test if the association between greenspace and PTSD trajectory was mediated by neural reactivity to reward. Design, Setting, and Participants: As part of a longitudinal cohort study, trauma survivors were recruited from emergency departments across the US. Two weeks after trauma, a subset of participants underwent functional magnetic resonance imaging during a monetary reward task. Study data were analyzed from January to November 2023. Exposures: Residential greenspace within a 100-m buffer of each participant's home address was derived from satellite imagery and quantified using the Normalized Difference Vegetation Index and perceived individual resources measured by the Connor-Davidson Resilience Scale (CD-RISC). Main Outcome and Measures: PTSD symptom severity measured at 2 weeks, 8 weeks, 3 months, and 6 months after trauma. Neural responses to monetary reward in reward-related regions (ie, amygdala, nucleus accumbens, orbitofrontal cortex) was a secondary outcome. Covariates included both geocoded (eg, area deprivation index) and self-reported characteristics (eg, childhood maltreatment, income). Results: In 2597 trauma survivors (mean [SD] age, 36.5 [13.4] years; 1637 female [63%]; 1304 non-Hispanic Black [50.2%], 289 Hispanic [11.1%], 901 non-Hispanic White [34.7%], 93 non-Hispanic other race [3.6%], and 10 missing/unreported [0.4%]), 6 PTSD trajectories (resilient, nonremitting high, nonremitting moderate, slow recovery, rapid recovery, delayed) were identified through latent-class mixed-effect modeling. Multinominal logistic regressions revealed that for individuals with higher CD-RISC scores, greenspace was associated with a greater likelihood of assignment in a resilient trajectory compared with nonremitting high (Wald z test = -3.92; P < .001), nonremitting moderate (Wald z test = -2.24; P = .03), or slow recovery (Wald z test = -2.27; P = .02) classes. Greenspace was also associated with greater neural reactivity to reward in the amygdala (n = 288; t277 = 2.83; adjusted P value = 0.02); however, reward reactivity did not differ by PTSD trajectory. Conclusions and Relevance: In this cohort study, greenspace and self-reported individual resources were significantly associated with PTSD trajectories. These findings suggest that factors at multiple ecological levels may contribute to the likelihood of resiliency to PTSD after trauma.
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Background: The occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, the impact of trauma, or the sequelae of PTSD itself. These effects include differences in DNA methylation (DNAm), an important form of epigenetic gene regulation, at multiple CpG loci across the genome. Moreover, these effects can be shared or specific to both central and peripheral tissues. Here, we aim to identify blood DNAm differences associated with PTSD and characterize the underlying biological mechanisms by examining the extent to which they mirror associations across multiple brain regions. Methods: As the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup, we conducted the largest cross-sectional meta-analysis of epigenome-wide association studies (EWASs) of PTSD to date, involving 5077 participants (2156 PTSD cases and 2921 trauma-exposed controls) from 23 civilian and military studies. PTSD diagnosis assessments were harmonized following the standardized guidelines established by the PGC-PTSD Workgroup. DNAm was assayed from blood using either Illumina HumanMethylation450 or MethylationEPIC (850K) BeadChips. A common QC pipeline was applied. Within each cohort, DNA methylation was regressed on PTSD, sex (if applicable), age, blood cell proportions, and ancestry. An inverse variance-weighted meta-analysis was performed. We conducted replication analyses in tissue from multiple brain regions, neuronal nuclei, and a cellular model of prolonged stress. Results: We identified 11 CpG sites associated with PTSD in the overall meta-analysis (1.44e-09 < p < 5.30e-08), as well as 14 associated in analyses of specific strata (military vs civilian cohort, sex, and ancestry), including CpGs in AHRR and CDC42BPB. Many of these loci exhibit blood-brain correlation in methylation levels and cross-tissue associations with PTSD in multiple brain regions. Methylation at most CpGs correlated with their annotated gene expression levels. Conclusions: This study identifies 11 PTSD-associated CpGs, also leverages data from postmortem brain samples, GWAS, and genome-wide expression data to interpret the biology underlying these associations and prioritize genes whose regulation differs in those with PTSD.