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BACKGROUND: Exposure to air pollution post lung transplant has been shown to decrease graft and patient survival. This study examines the impact of air pollution exposure in the first 3 months post-transplant on baseline (i.e. highest) forced expiratory volume in 1s (FEV1) achieved and development of chronic lung allograft dysfunction (CLAD). METHODS: Double-lung transplant recipients (n=82) were prospectively enrolled for comprehensive indoor and personal environmental monitoring at 6- and 12-weeks post-transplant and followed for >4 years. Associations between clinical and exposure variables were investigated using an exposomics approach followed by analysis with a Cox Proportional Hazards model. Multivariable analyses were used to examine the impact of air pollution on baseline % predicted FEV1 (defined as the average of the 2 highest values achieved post-transplant) and risk of CLAD. RESULTS: Multivariable analysis revealed a significant inverse relationship between personal black carbon (BC) levels and baseline % FEV1. The multivariable model indicated that patients with higher-than-median exposure to BC (>350 ng/m3) attained a baseline % FEV1 that was 8.8% lower than those with lower-than-median BC exposure (p = 0.019). Cox proportional hazards model analysis revealed that patients with high personal BC exposure had a 2.4 times higher hazard risk for CLAD than patients with low BC exposure (p = 0.045). CONCLUSIONS: Higher personal BC levels during the first 3 months post-transplant decreases baseline FEV1 and doubles the risk of CLAD. Strategies to reduce BC exposure early following lung transplant may help improve lung function and long-term outcomes.
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Background: Abnormalities in white matter development may influence development of autism spectrum disorder in tuberous sclerosis complex (TSC). Our goals for this study were as follows: (1) use data from a longitudinal neuroimaging study of tuberous sclerosis complex (TACERN) to develop optimized linear mixed effects models for analyzing longitudinal, repeated diffusion tensor imaging metrics (fractional anisotropy, mean diffusivity) pertaining to select white matter tracts, in relation to positive Autism Diagnostic Observation Schedule-Second Edition classification at 36 months, and (2) perform an exploratory analysis using optimized models applied to all white matter tracts from these data. Methods: Eligible participants (3-12 months) underwent brain magnetic resonance imaging (MRI) at repeated time points from ages 3 to 36 months. Positive Autism Diagnostic Observation Schedule-Second Edition classification at 36 months was used. Linear mixed effects models were fine-tuned separately for fractional anisotropy values (using fractional anisotropy corpus callosum as test outcome) and mean diffusivity values (using mean diffusivity right posterior limb internal capsule as test outcome). Fixed effects included participant age, within-participant longitudinal age, and autism spectrum disorder diagnosis. Results: Analysis included data from n = 78. After selecting separate optimal models for fractional anisotropy and mean diffusivity values, we applied these models to fractional anisotropy and mean diffusivity of all 27 white matter tracts. Fractional anisotropy corpus callosum was related to positive Autism Diagnostic Observation Schedule-Second Edition classification (coefficient = 0.0093, P = .0612), and mean diffusivity right inferior cerebellar peduncle was related to positive Autism Diagnostic Observation Schedule-Second Edition classification (coefficient = -0.00002071, P = .0445), though these findings were not statistically significant after multiple comparisons correction. Conclusion: These optimized linear mixed effects models possibly implicate corpus callosum and cerebellar pathology in development of autism spectrum disorder in tuberous sclerosis complex, but future studies are needed to replicate these findings and explore contributors of heterogeneity in these models.
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Trastorno del Espectro Autista , Imagen de Difusión Tensora , Esclerosis Tuberosa , Sustancia Blanca , Humanos , Esclerosis Tuberosa/diagnóstico por imagen , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/patología , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno del Espectro Autista/patología , Imagen de Difusión Tensora/métodos , Masculino , Femenino , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Estudios Longitudinales , Preescolar , Lactante , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/crecimiento & desarrollo , AnisotropíaRESUMEN
Oscillometry is an emerging pulmonary function testing tool that is conducted during tidal breaths with minimal patient effort. It is highly sensitive to changes in lung mechanics. Oscillometry was recently shown to be highly associated with disease severity in idiopathic pulmonary fibrosis (IPF). The usefulness of oscillometry after single lung transplant in IPF patients is not well understood. Our study demonstrated that oscillometry can detect changes in the graft despite presence of a native fibrotic lung to provide useful information to complement spirometry.
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Introduction: Prior studies assessing outcomes of lung transplants from cigarette-smoking donors found mixed results. Oscillometry, a non-invasive test of respiratory impedance, detects changes in lung function of smokers prior to diagnosis of COPD, and identifies spirometrically silent episodes of rejection post-transplant. We hypothesise that oscillometry could identify abnormalities in recipients of smoking donor lungs and discriminate from non-smoking donors. Methods: This prospective single-center cohort study analysed 233 double-lung recipients. Oscillometry was performed alongside routine conventional pulmonary function tests (PFT) post-transplant. Multivariable regression models were constructed to compare oscillometry and conventional PFT parameters between recipients of lungs from smoking vs non-smoking donors. Results: The analysis included 109 patients who received lungs from non-smokers and 124 from smokers. Multivariable analysis identified significant differences between recipients of smoking and non-smoking lungs in the oscillometric measurements R5-19, X5, AX, R5z and X5z, but no differences in %predicted FEV1, FEV1/FVC, %predicted TLC or %predicted DLCO. An analysis of the smoking group also demonstrated associations between increasing smoke exposure, quantified in pack years, and all the oscillometry parameters, but not the conventional PFT parameters. Conclusion: An interaction was identified between donor-recipient sex match and the effect of smoking. The association between donor smoking and oscillometry outcomes was significant predominantly in the female donor/female recipient group.
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Common genetic variants identified in the general population have been found to increase phenotypic risks among individuals with certain genetic conditions. Up to 90% of individuals with tuberous sclerosis complex (TSC) are affected by some type of epilepsy, yet the common variants contributing to epilepsy risk in the general population have not been evaluated in the context of TSC-associated epilepsy. Such knowledge is important to help uncover the underlying pathogenesis of epilepsy in TSC which is not fully understood, and critical as uncontrolled epilepsy is a major problem in this population. To evaluate common genetic modifiers of epilepsy, our study pooled phenotypic and genotypic data from 369 individuals with TSC to evaluate known and novel epilepsy common variants. We did not find evidence of enhanced genetic penetrance for known epilepsy variants identified across the largest genome-wide association studies of epilepsy in the general population, but identified support for novel common epilepsy variants in the context of TSC. Specifically, we have identified a novel signal in SLC7A1 that may be functionally involved in pathways relevant to TSC and epilepsy. Our study highlights the need for further evaluation of genetic modifiers in TSC to aid in further understanding of epilepsy in TSC and improve outcomes.
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Epilepsia , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Esclerosis Tuberosa , Humanos , Esclerosis Tuberosa/genética , Esclerosis Tuberosa/complicaciones , Epilepsia/genética , Epilepsia/epidemiología , Femenino , Masculino , Adulto , Variación Genética , Genotipo , Adolescente , Fenotipo , Niño , Polimorfismo de Nucleótido Simple , PreescolarRESUMEN
OBJECTIVE: The purpose of this study was to explore the experiences of nurses who responded to a public mass shooting in 2017. METHODS: This qualitative study was conducted with a sample of nurses who responded to a mass shooting, recruited purposively from a hospital in Las Vegas, Nevada. Intensive interviews were conducted with a total of 7 nurses, audio-recorded and transcribed for thematic analysis. RESULTS: Six themes were developed from interview data: (1) "The worst night of my life": Overrun and overwhelmed; (2) Unexpected altruism and benevolence of patients and staff; (3) "The Wild West": Giving victim care by improvising beyond rules; (4) Experiencing a range of reactions in the immediate aftermath and in the long term; (5) Shifts in nursing practice and evolving team dynamics; and (6) Defining realistic approaches to support staff mental health and mass casualty preparation. CONCLUSION: Nurses who were involved in responding to the public mass shooting described the event as life-altering. Given the critical role of nurses in responding to mass shootings, it is essential to consider how nurses can be supported in the aftermath of these events and how mass disaster preparation can include attention to the needs of nurses.
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Altruismo , Desastres , Humanos , Hospitales , Salud Mental , Investigación CualitativaRESUMEN
Neurodevelopment in the first 10 years of life is a critical time window during which milestones that define an individual's functional potential are achieved. Comprehensive multimodal neurodevelopmental monitoring is particularly crucial for socioeconomically disadvantaged, marginalized, historically underserved and underrepresented communities as well as medically underserved areas. Solutions designed for use outside the traditional clinical environment represent an opportunity for addressing such health inequalities. In this work, we present an experimental platform, ANNE EEG, which adds 16-channel cerebral activity monitoring to the existing, USA FDA-cleared ANNE wireless monitoring platform which provides continuous electrocardiography, respiratory rate, pulse oximetry, motion, and temperature measurements. The system features low-cost consumables, real-time control and streaming with widely available mobile devices, and fully wearable operation to allow a child to remain in their naturalistic environment. This multi-center pilot study successfully collected ANNE EEG recordings from 91 neonatal and pediatric patients at academic quaternary pediatric care centers and in LMIC settings. We demonstrate the practicality and feasibility to conduct electroencephalography studies with high levels of accuracy, validated via both quantitative and qualitative metrics, compared against gold standard systems. An overwhelming majority of parents surveyed during studies indicated not only an overall preference for the wireless system, but also that its use would improve their children's physical and emotional health. Our findings demonstrate the potential for the ANNE system to perform multimodal monitoring to screen for a variety of neurologic diseases that have the potential to negatively impact neurodevelopment.
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A property-focused optimization strategy was employed to modify the carboxylic acid head group of a class of EP4 agonists in order to minimize its absorption upon oral administration. The resulting oxalic acid monohydrazide-derived carboxylate isostere demonstrated utility as a class of prodrug showing colon-targeted delivery of parent agonist 2, with minimal exposure observed in the plasma. Oral administration of NXT-10796 demonstrated tissue specific activation of the EP4 receptor through modulation of immune genes in the colon, without modulation of EP4 driven biomarkers in the plasma compartment. Although further in depth understanding of the conversion of NXT-10796 is required for further assessment of the developability of this series of prodrugs, using NXT-10796 as a tool molecule has allowed us to confirm that tissue-specific modulation of an EP4-modulated gene signature is possible, which allows for further evaluation of this therapeutic modality in rodent models of human disease.
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Enfermedades Inflamatorias del Intestino , Profármacos , Humanos , Profármacos/farmacología , Profármacos/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Colon , Subtipo EP4 de Receptores de Prostaglandina E/agonistasRESUMEN
Background: Chronic lung allograft dysfunction (CLAD) is the major cause of death post-lung transplantation, with acute cellular rejection (ACR) being the biggest contributing risk factor. Although patients are routinely monitored with spirometry, FEV1 is stable or improving in most ACR episodes. In contrast, oscillometry is highly sensitive to respiratory mechanics and shown to track graft injury associated with ACR and its improvement following treatment. We hypothesize that intra-subject variability in oscillometry measurements correlates with ACR and risk of CLAD. Methods: Of 289 bilateral lung recipients enrolled for oscillometry prior to laboratory-based spirometry between December 2017 and March 2020, 230 had ≥ 3 months and 175 had ≥ 6 months of follow-up. While 37 patients developed CLAD, only 29 had oscillometry at time of CLAD onset and were included for analysis. These 29 CLAD patients were time-matched with 129 CLAD-free recipients. We performed multivariable regression to investigate the associations between variance in spirometry/oscillometry and the A-score, a cumulative index of ACR, as our predictor of primary interest. Conditional logistic regression models were built to investigate associations with CLAD. Results: Multivariable regression showed that the A-score was positively associated with the variance in oscillometry measurements. Conditional logistic regression models revealed that higher variance in the oscillometry metrics of ventilatory inhomogeneity, X5, AX, and R5-19, was independently associated with increased risk of CLAD (p < 0.05); no association was found for variance in %predicted FEV1. Conclusion: Oscillometry tracks graft injury and recovery post-transplant. Monitoring with oscillometry could facilitate earlier identification of graft injury, prompting investigation to identify treatable causes and decrease the risk of CLAD.
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This study demonstrates the inadequacy of the current technical standards of oscillometry that are based on the within-trial reproducibility of the lowest-frequency Rrs, and suggests the use of a simple variability measure encompassing both Rrs and Xrs https://bit.ly/3AYRid6.
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OBJECTIVE: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a commonly used clinical method of destroying intracranial brain foci. Our objective was to correlate the thermal damage estimate transition zone with cognitive outcomes in MRgLITT of a pediatric hypothalamic hamartoma. METHODS: Uncomplicated MRgLITT was used to disconnect an 8-mm left Delalande grade II hypothalamic hamartoma (HH) revealed on neuroimaging of a 17-year-old male patient with drug-resistant epilepsy and a "gelastic +" semiology including both gelastic and tonic-clonic seizures. Despite meticulous planning, submillimetric stereotactic accuracy, and reassuring intraoperative thermography, the patient experienced transient, but profound, global amnesia. Retroactively, we applied a new iteration of thermographic software that overlays a magenta-colored transition zone (TZ) around the necrotic zone defined by the orange-pigmented thermal damage estimate (TDE). RESULTS: Clear involvement of the bilateral mesial circuits was demonstrated by the overlay of the TZ on the TDE. CONCLUSIONS: Involvement of the bilateral mesial circuits visualized with TDE and TZ could account for the neurocognitive outcomes of our patient. We highlight this case as our understanding of thermography analysis evolves, emphasizing principles of technique and trajectory planning, as well as considerations during thermablation to help inform surgical decision-making.
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BACKGROUND: Abnormal brain growth in tuberous sclerosis complex (TSC) reflects abnormalities in cellular proliferation and differentiation and results in epilepsy and other neurological manifestations. Head circumference (HC) as a proxy for brain volume may provide an easily tracked clinical measure of brain overgrowth and neurological disease burden. This study investigated the relationship between HC and epilepsy severity in infants with TSC. METHODS: Prospective multicenter observational study of children from birth to three years with TSC. Epilepsy data were collected from clinical history, and HC was collected at study visits at age three, six, nine, 12, 18, 24, and 36 months. Epilepsy severity was classified as no epilepsy, low epilepsy severity (one seizure type and one or two antiepileptic drugs [AEDs]), moderate epilepsy severity (either two to three seizure types and one to two AEDs or one seizure type and more than three AEDs), or high epilepsy severity (two to three seizure types and more than three AEDs). RESULTS: As a group, children with TSC had HCs approximately 1 S.D. above the mean World Health Organization (WHO) reference by age one year and demonstrated more rapid growth than the normal population reference. Males with epilepsy had larger HCs than those without. Compared with the WHO reference population, infants with TSC and no epilepsy or low or moderate epilepsy had an increased early HC growth rate, whereas those with severe epilepsy had an early larger HC but did not have a faster growth rate. CONCLUSIONS: Infants and young children with TSC have larger HCs than typical growth norms and have differing rates of head growth depending on the severity of epilepsy.
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Epilepsia , Esclerosis Tuberosa , Niño , Masculino , Humanos , Lactante , Preescolar , Esclerosis Tuberosa/tratamiento farmacológico , Estudios Prospectivos , Epilepsia/etiología , Epilepsia/complicaciones , Anticonvulsivantes/uso terapéutico , Convulsiones/tratamiento farmacológicoRESUMEN
BACKGROUND: The associations between body flexibility and sarcopenia were not well understood. This study aimed to explore the cross-sectional and longitudinal associations of flexibility with sarcopenia. METHODS: Our study selected participants aged 50-80 from the WELL-China cohort and the Lanxi cohort. Participants from the urban area of the Lanxi cohort were followed up 4 years later. Body flexibility was measured by the sit-and-reach test. Muscle mass was evaluated by dual-energy X-ray absorptiometry. Muscle strength was evaluated using handgrip strength. Sarcopenia was defined as having both low muscle mass and low muscle strength. We used multivariable logistic regressions to assess the cross-sectional associations of body flexibility with low muscle mass, low muscle strength and sarcopenia. We also used multivariable logistic regressions to explore the associations of baseline flexibility and 4-year changes in flexibility with incident low muscle mass, low muscle strength and sarcopenia. RESULTS: A total of 9453 participants were enrolled in the cross-sectional study, and 1233 participants were included in the longitudinal analyses. In the cross-sectional analyses, compared with low body flexibility, high body flexibility was inversely associated with low muscle mass (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.50-0.68; P < 0.001), low muscle strength (OR, 0.62; 95% CI, 0.55-0.69; P < 0.001) and sarcopenia (OR, 0.52; 95% CI, 0.41-0.65; P < 0.001), and these associations did not differ in different age groups, sex or physical activity levels. In the longitudinal analyses, compared with participants with low body flexibility, participants with high body flexibility had lower risk of the incident low muscle strength (OR, 0.53; 95% CI, 0.38-0.74; P < 0.001) and sarcopenia (OR, 0.36; 95% CI, 0.21-0.61; P < 0.001), but not incident low muscle mass (OR, 0.59; 95% CI, 0.33-1.06; P = 0.076). Every 1-cm increase in flexibility during 4 years was associated with reduced risk of incident low muscle mass (OR, 0.96; 95% CI, 0.93-1.00; P = 0.025), low muscle strength (OR, 0.96; 95% CI, 0.94-0.98; P = 0.002) and sarcopenia (OR, 0.96; 95% CI, 0.93-0.99; P = 0.007). CONCLUSIONS: High flexibility was associated with reduced risk of incident low muscle strength and sarcopenia. Increases in flexibility were associated with reduced risk of incident low muscle mass, low muscle strength and sarcopenia. Flexibility exercises and monitoring the dynamic change of flexibility might be helpful in preventing sarcopenia among adults aged 50 years or over.
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Sarcopenia , Adulto , Humanos , Sarcopenia/epidemiología , Estudios Transversales , Fuerza de la Mano , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/fisiología , Fuerza Muscular/fisiologíaRESUMEN
OBJECTIVE: Tuberous sclerosis complex (TSC) is associated with focal brain "tubers" and a high incidence of autism spectrum disorder (ASD). The location of brain tubers associated with autism may provide insight into the neuroanatomical substrate of ASD symptoms. METHODS: We delineated tuber locations for 115 TSC participants with ASD (n = 31) and without ASD (n = 84) from the Tuberous Sclerosis Complex Autism Center of Excellence Research Network. We tested for associations between ASD diagnosis and tuber burden within the whole brain, specific lobes, and at 8 regions of interest derived from the ASD neuroimaging literature, including the anterior cingulate, orbitofrontal and posterior parietal cortices, inferior frontal and fusiform gyri, superior temporal sulcus, amygdala, and supplemental motor area. Next, we performed an unbiased data-driven voxelwise lesion symptom mapping (VLSM) analysis. Finally, we calculated the risk of ASD associated with positive findings from the above analyses. RESULTS: There were no significant ASD-related differences in tuber burden across the whole brain, within specific lobes, or within a priori regions derived from the ASD literature. However, using VLSM analysis, we found that tubers involving the right fusiform face area (FFA) were associated with a 3.7-fold increased risk of developing ASD. INTERPRETATION: Although TSC is a rare cause of ASD, there is a strong association between tuber involvement of the right FFA and ASD diagnosis. This highlights a potentially causative mechanism for developing autism in TSC that may guide research into ASD symptoms more generally. ANN NEUROL 2023;93:577-590.
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Trastorno del Espectro Autista , Trastorno Autístico , Esclerosis Tuberosa , Humanos , Trastorno del Espectro Autista/patología , Esclerosis Tuberosa/complicaciones , Encéfalo/patología , Neuroimagen , Imagen por Resonancia Magnética/métodosRESUMEN
RATIONALE: Spirometry and plethysmography are the gold standard pulmonary function tests (PFT) for diagnosis and management of lung disease. Due to the inaccessibility of plethysmography, spirometry is often used alone but this leads to missed or misdiagnoses as spirometry cannot identify restrictive disease without plethysmography. We aimed to develop a deep learning model to improve interpretation of spirometry alone. METHODS: We built a multilayer perceptron model using full PFTs from 748 patients, interpreted according to international guidelines. Inputs included spirometry (forced vital capacity, forced expiratory volume in 1 s, forced mid-expiratory flow25-75), plethysmography (total lung capacity, residual volume) and biometrics (sex, age, height). The model was developed with 2582 PFTs from 477 patients, randomly divided into training (80%), validation (10%) and test (10%) sets, and refined using 1245 previously unseen PFTs from 271 patients, split 50/50 as validation (136 patients) and test (135 patients) sets. Only one test per patient was used for each of 10 experiments conducted for each input combination. The final model was compared with interpretation of 82 spirometry tests by 6 trained pulmonologists and a decision tree. RESULTS: Accuracies from the first 477 patients were similar when inputs included biometrics+spirometry+plethysmography (95%±3%) vs biometrics+spirometry (90%±2%). Model refinement with the next 271 patients improved accuracies with biometrics+pirometry (95%±2%) but no change for biometrics+spirometry+plethysmography (95%±2%). The final model significantly outperformed (94.67%±2.63%, p<0.01 for both) interpretation of 82 spirometry tests by the decision tree (75.61%±0.00%) and pulmonologists (66.67%±14.63%). CONCLUSIONS: Deep learning improves the diagnostic acumen of spirometry and classifies lung physiology better than pulmonologists with accuracies comparable to full PFTs.
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Aprendizaje Profundo , Humanos , Canadá , Espirometría , Pruebas de Función Respiratoria , PercepciónRESUMEN
Background: Chronic lung allograft dysfunction (CLAD) is the major cause of death beyond 2 years after lung transplantation and develops in 50% of all patients by 5 years post-transplant. CLAD is diagnosed on the basis of a sustained drop of 20% for at least 3 months in the forced expiratory volume (FEV1), compared to the best baseline value achieved post-transplant. CLAD presents as two main phenotypes: bronchiolitis obliterans syndrome (BOS) is more common and has better prognosis than restrictive allograft syndrome (RAS). Respiratory oscillometry is a different modality of lung function testing that is highly sensitive to lung mechanics. The current study investigated whether spectral and intrabreath oscillometry can differentiate between CLAD-free, BOS- and RAS-CLAD at CLAD onset, i.e., at the time of the initial 20% drop in the FEV1. Methods: A retrospective, cross-sectional analysis of 263 double lung transplant recipients who underwent paired testing with oscillometry and spirometry at the Toronto General Pulmonary Function Laboratory from 2017 to 2022 was conducted. All pulmonary function testing and CLAD diagnostics were performed following international guidelines. Statistical analysis was conducted using multiple comparisons. Findings: The RAS (n = 6) spectral oscillometry pattern differs from CLAD-free (n = 225) by right-ward shift of reactance curve similar to idiopathic pulmonary fibrosis whereas BOS (n = 32) has a pattern similar to obstructive lung disease. Significant differences were found in most spectral and intrabreath parameters between BOS, RAS, and time-matched CLAD-free patients. Post-hoc analysis revealed these differences were primarily driven by BOS instead of RAS. While no differences were found between CLAD-free and RAS patients with regards to spectral oscillometry, the intrabreath metric of reactance at end-inspiration (XeI) was significantly different (p < 0.05). BOS and RAS were differentiated by spectral oscillometry measure R5, and intrabreath resistance at end expiration, ReE (p < 0.05 for both). Conclusion: Both spectral and intrabreath oscillometry can differentiate BOS-CLAD from CLAD-free states while intrabreath oscillometry, specifically XeI, can uniquely distinguish RAS-CLAD from CLAD-free. Spectral and intrabreath oscillometry offer complementary information regarding lung mechanics in CLAD patients to help distinguish the two phenotypes and could prove useful in prognostication.
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Increasing evidence has shown that summary visual statistics, such as the mean size or centroid of locations, can be perceived without focal attention. Here, we tested the role of attention in visual category learning - rapid learning of visual similarities among paintings of the same artist. Participants encoded paintings from two famous artists into memory while simultaneously monitoring a rapid serial visual presentation (RSVP) stream of colored squares, pressing the spacebar for target colors and making no response to distractor colors. Paintings encoded with the RSVP targets were better remembered than those encoded with the RSVP distractors, demonstrating an Attentional Boost Effect. Importantly, pairing one artist's paintings with the RSVP targets led to better visual category learning - participants were more accurate at recognizing novel paintings from this artist, relative to another artist whose paintings were presented with the RSVP distractors. Thus, visual category learning is subjected to the same constraint of attention as exemplar memory, demonstrating common mechanisms for exemplar and category learning.
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Atención , Recuerdo Mental , Humanos , Aprendizaje EspacialRESUMEN
BACKGROUND AND PURPOSE: The success of epilepsy surgery in children with tuberous sclerosis complex (TSC) hinges on identification of the epileptogenic zone (EZ). We studied structural MRI markers of epileptogenic lesions in young children with TSC. METHODS: We included 26 children with TSC who underwent epilepsy surgery before the age of 3 years at five sites, with 12 months or more follow-up. Two neuroradiologists, blinded to surgical outcome data, reviewed 10 candidate lesions on preoperative MRI for characteristics of the tuber (large affected area, calcification, cyst-like properties) and of focal cortical dysplasia (FCD) features (cortical malformation, gray-white matter junction blurring, transmantle sign). They selected lesions suspect for the EZ based on structural MRI, and reselected after unblinding to seizure onset location on electroencephalography (EEG). RESULTS: None of the tuber characteristics and FCD features were distinctive for the EZ, indicated by resected lesions in seizure-free children. With structural MRI alone, the EZ was identified out of 10 lesions in 31%, and with addition of EEG data, this increased to 48%. However, rates of identification of resected lesions in non-seizure-free children were similar. Across 251 lesions, interrater agreement was moderate for large size (κ = .60), and fair (κ = .24) for all other features. CONCLUSIONS: In young children with TSC, the utility of structural MRI features is limited in the identification of the epileptogenic tuber, but improves when combined with EEG data.
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Epilepsia , Malformaciones del Desarrollo Cortical , Esclerosis Tuberosa , Niño , Preescolar , Electroencefalografía/métodos , Epilepsia/diagnóstico por imagen , Epilepsia/cirugía , Humanos , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/diagnóstico por imagen , Esclerosis Tuberosa/cirugíaRESUMEN
BACKGROUND: Markers of idiopathic pulmonary fibrosis (IPF) severity are based on measurements of forced vital capacity (FVC), diffusing capacity (DLCO) and CT. The pulmonary vessel volume (PVV) is a novel quantitative and independent prognostic structural indicator derived from automated CT analysis. The current prospective cross-sectional study investigated whether respiratory oscillometry provides complementary data to pulmonary function tests (PFTs) and is correlated with PVV. METHODS: From September 2019 to March 2020, we enrolled 89 patients with IPF diagnosed according to international guidelines. We performed standard spectral (5-37 Hz) and novel intrabreath tracking (10 Hz) oscillometry followed by PFTs. Patients were characterised with the gender-age-physiology (GAP) score. CT images within 6 months of oscillometry were analysed in a subgroup (26 patients) using automated lung texture analysis. Correlations between PFTs, oscillometry and imaging variables were investigated using different regression models. FINDINGS: The cohort (29F/60M; age=71.7±7.8 years) had mild IPF (%FVC=70±17, %DLCO=62±17). Spectral oscillometry revealed normal respiratory resistance, low reactance, especially during inspiration at 5 Hz (X5in), elevated reactance area and resonance frequency. Intrabreath oscillometry identified markedly low reactance at end-inspiration (XeI). XeI and X5in strongly correlated with FVC (r2=0.499 and 0.435) while XeI was highly (p=0.004) and uniquely correlated with the GAP score. XeI and PVV exhibited the strongest structural-functional relationship (r2=0.690), which remained significant after adjusting for %FVC, %DLCO and GAP score. INTERPRETATION: XeI is an independent marker of IPF severity that offers additional information to standard PFTs. The data provide a cogent rationale for adding oscillometry in IPF assessment.
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Fibrosis Pulmonar Idiopática , Anciano , Estudios Transversales , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Persona de Mediana Edad , Oscilometría , Pruebas de Función Respiratoria , Tomografía Computarizada por Rayos X/métodosRESUMEN
Respiratory oscillometry is a different modality of pulmonary function testing that is increasingly used in a clinical and research setting to provide information regarding lung mechanics. Respiratory oscillometry is conducted through three acceptable measurements of tidal breathing and can be performed with minimal contraindications. Young children and patients who cannot perform spirometry due to cognitive or physical impairment can usually complete oscillometry. The main advantages of respiratory oscillometry are that it requires minimal patient cooperation and is more sensitive in detecting changes in small airways than conventional pulmonary function tests. Commercial devices are now available. Updated technical guidelines, standard operating protocols, and quality control/assurance guidelines have recently been published. Reference values are also available. We conducted oscillometry test audits before and after implementing a formal respiratory oscillometry training program and standard operating protocol. We observed improvement in the quality of tests completed, with a significant increase in the number of acceptable and reproducible measurements. The current paper outlines and demonstrates a standard operating protocol to conduct respiratory oscillometry in an outpatient setting. We highlight the key steps to ensuring acceptable and reproducible quality measurements according to the recommended European Respiratory Society (ERS) guidelines, as quality control is critical to measurement accuracies. Potential problems and pitfalls are also discussed with suggestions to resolve technical errors.