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1.
Mult Scler ; 29(6): 691-701, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36507671

RESUMEN

BACKGROUND: We evaluated imaging features suggestive of neurodegeneration within the brainstem and upper cervical spinal cord (UCSC) in non-progressive multiple sclerosis (MS). METHODS: Standardized 3-Tesla three-dimensional brain magnetic resonance imaging (MRI) studies were prospectively acquired. Rates of change in volume, surface texture, curvature were quantified at the pons and medulla-UCSC. Whole and regional brain volumes and T2-weighted lesion volumes were also quantified. Independent regression models were constructed to evaluate differences between those of Black or African ancestry (B/AA) and European ancestry (EA) with non-progressive MS. RESULTS: 209 people with MS (pwMS) having at least two MRI studies, 29% possessing 3-6 timepoints, resulted in 487 scans for analysis. Median follow-up time between MRI timepoints was 1.33 (25th-75th percentile: 0.51-1.98) years. Of 183 non-progressive pwMS, 88 and 95 self-reported being B/AA and EA, respectively. Non-progressive pwMS demonstrated greater rates of decline in pontine volume (p < 0.0001) in B/AA and in medulla-UCSC volume (p < 0.0001) for EA pwMS. Longitudinal surface texture and curvature changes suggesting reduced tissue integrity were observed at the ventral medulla-UCSC (p < 0.001), dorsal pons (p < 0.0001) and dorsal medulla (p < 0.0001) but not the ventral pons (p = 0.92) between groups. CONCLUSIONS: Selectively vulnerable regions within the brainstem-UCSC may allow for more personalized approaches to disease surveillance and management.


Asunto(s)
Médula Cervical , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Médula Cervical/patología , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Negro o Afroamericano , Médula Espinal/diagnóstico por imagen , Médula Espinal/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Tronco Encefálico/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/patología
2.
J Neuroimaging ; 32(6): 1090-1097, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36181675

RESUMEN

BACKGROUND AND PURPOSE: The timely and accurate diagnosis of neuromyelitis optica spectrum disorder (NMOSD) is essential and exposure to multiple sclerosis (MS) disease-modifying therapies may result in permanent neurological disability. METHODS: Standardized 3-Tesla 3-dimensional brain MRI studies were retrospectively studied from people with NMOSD, MS, other CNS neurological diseases, and healthy control subjects. Comparisons of surface texture characteristics at the area postrema involving absolute introverted planar triangle counts, representing more complex and concave tissue topography, along with the spatial dissemination pattern of these triangles were performed cross-sectionally and longitudinally. An ideal introverted planar triangle threshold separating groups with NMOSD and MS was accomplished using the highest Youden's J statistic. For the classification of NMOSD, out-of-sample and in-sample measurements of the following were acquired: sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: The study cohort included 60 people with NMOSD, 100 people with MS, 12 with other neurological diseases, and five healthy controls. Significantly higher cross-sectional median introverted triangle counts were observed when the NMOSD (median [interquartile range]: 100 [23.5]) group was compared to MS (65 [20.25]; p < .0001) and other neurological diseases (66 [13.75]; p < .0001). Distinct spatial dissemination patterns of triangles extending craniocaudally at the region of interest within the dorsal medulla was also seen between groups with NMOSD and MS (p < .0001). For the identification of NMOSD, out-of-sample sensitivity (83%), specificity (100%), PPV (100%), and NPV (60%) were achieved. CONCLUSIONS: Cross-sectional and longitudinal dorsal medulla surface texture differences within selective regions of vulnerability differentiate NMOSD from MS.


Asunto(s)
Esclerosis Múltiple , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/diagnóstico por imagen , Esclerosis Múltiple/diagnóstico por imagen , Estudios Transversales , Estudios Retrospectivos , Imagen por Resonancia Magnética
3.
PLoS One ; 17(8): e0272364, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35947606

RESUMEN

Neutralizing antibodies targeting the SARS-CoV-2 spike protein have shown a great preventative/therapeutic potential. Here, we report a rapid and efficient strategy for the development and design of SARS-CoV-2 neutralizing humanized nanobody constructs with sub-nanomolar affinities and nanomolar potencies. CryoEM-based structural analysis of the nanobodies in complex with spike revealed two distinct binding modes. The most potent nanobody, RBD-1-2G(NCATS-BL8125), tolerates the N501Y RBD mutation and remains capable of neutralizing the B.1.1.7 (Alpha) variant. Molecular dynamics simulations provide a structural basis for understanding the neutralization process of nanobodies exclusively focused on the spike-ACE2 interface with and without the N501Y mutation on RBD. A primary human airway air-lung interface (ALI) ex vivo model showed that RBD-1-2G-Fc antibody treatment was effective at reducing viral burden following WA1 and B.1.1.7 SARS-CoV-2 infections. Therefore, this presented strategy will serve as a tool to mitigate the threat of emerging SARS-CoV-2 variants.


Asunto(s)
Bacteriófagos , COVID-19 , Anticuerpos de Dominio Único , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Bacteriófagos/metabolismo , Humanos , Unión Proteica , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus
4.
J Neurol ; 269(8): 4459-4468, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35380254

RESUMEN

BACKGROUND AND PURPOSE: Differentiating between multiple sclerosis (MS) and small vessel disease (SVD) lesions represents a key challenge in the day-to-day management of patients. We aimed to distinguish between MS and SVD by identifying the dynamics of lesion movement patterns between enlarging and contracting foci from two MRI time points. METHODS: Standardized 3-Tesla 3-dimensional brain magnetic resonance imaging (MRI) studies were performed at two time points on enrolled MS and SVD patients. Selected supratentorial lesions were segmented and longitudinal changes in the direction of lesion displacement and magnitude along with the evolution of contracting and expanding T1-weighted and T2-weighted MS lesions were quantified based on lesion centroid positioning. Bayesian linear mixed effects regression models were constructed to evaluate associations between changes in lesion transitions and disease state. RESULTS: A total of 420 lesions were analyzed from 35 MS (female (F):22 (62.9%); median age (range):38 years (y) (22-61), median disease duration:7.38y (0.38-20.99)) and 12 SVD patients (F:11 (100%); 54y (40-66)). MS T2-weighted lesions that increased in volume between MRI time points demonstrated movement toward the cortex (p = 0.01), whereas those that decreased in volume moved toward the center (p < 0.0001). Lesion volume changes related to SVD demonstrated no effect on movement direction over time. Both expanding (p = 0.03) and contracting (p = 0.01) MS lesions demonstrated greater distances between centroids when compared to SVD. CONCLUSION: Lesion dynamics may reveal distinct characteristics associated with the biology of disease while providing further insights into the behavior of inflammatory CNS disorders.


Asunto(s)
Esclerosis Múltiple , Teorema de Bayes , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Corteza Cerebral/patología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología
5.
bioRxiv ; 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-34729560

RESUMEN

Neutralizing antibodies targeting the SARS-CoV-2 spike protein have shown a great preventative/therapeutic potential. Here, we report a rapid and efficient strategy for the development and design of SARS-CoV-2 neutralizing humanized nanobody constructs with sub-nanomolar affinities and nanomolar potencies. CryoEM-based structural analysis of the nanobodies in complex with spike revealed two distinct binding modes. The most potent nanobody, RBD-1-2G(NCATS-BL8125), tolerates the N501Y RBD mutation and remains capable of neutralizing the B.1.1.7 (Alpha) variant. Molecular dynamics simulations provide a structural basis for understanding the neutralization process of nanobodies exclusively focused on the spike-ACE2 interface with and without the N501Y mutation on RBD. A primary human airway air-lung interface (ALI) ex vivo model showed that RBD-1-2G-Fc antibody treatment was effective at reducing viral burden following WA1 and B.1.1.7 SARS-CoV-2 infections. Therefore, this presented strategy will serve as a tool to mitigate the threat of emerging SARS-CoV-2 variants.

6.
Vector Borne Zoonotic Dis ; 21(12): 921-940, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34757815

RESUMEN

The plague bacterium Yersinia pestis is lethal to endangered black-footed ferrets (Mustela nigripes, BFF) and the prairie dogs (Cynomys spp., PD) on which they depend for habitat and prey. We assessed the effectiveness of an oral sylvatic plague vaccine delivered in baits to black-tailed PD (Cynomys ludovicianus, BTPD) from 2013 to 2017 on the Charles M. Russell National Wildlife Refuge (CMR) in northcentral Montana. We permanently marked BTPD on four paired vaccine (N = 1,349 individuals) and placebo plots (N = 926; 7,027 total captures). We analyzed capture-recapture data under a Cormack-Jolly-Seber model to estimate annual apparent survival. Overall, survival averaged 0.05 lower on vaccine plots than on paired placebo plots. Immediately before noticeable die-offs and detecting plague on pairs CMR1 and CMR2, 89% of BTPD sampled on vaccine plots had consumed at least one bait and the immune systems (pleural) of 40% were likely boosted by consuming baits over multiple years. Survival to the following year was 0.16 and 0.05 on the vaccine plots and 0.19 and 0.06 on the placebo plots for pairs CMR1 and CMR2, respectively. These rates were markedly lower than 0.63, the overall average estimate on those same plots during the previous 3 years. PD populations subjected to such large die-offs would not be expected to sustain a BFF population. An overriding limitation to achieving sufficient protection rests with vaccine delivery constraints. Late summer/fall bait distribution results in the highest bait uptake rates. However, the PD birth pulse each spring can double the size of populations in most years, greatly reducing the proportion of vaccinates in populations and diminishing potential herd immunity benefits. In addition to nonvaccinated juveniles and PD that do not consume bait, incomplete vaccine protection and time required for immunity to develop leaves a large majority of PD populations vulnerable to plague for 6-7 months or more each year.


Asunto(s)
Vacuna contra la Peste , Enfermedades de los Roedores , Siphonaptera , Yersinia pestis , Animales , Hurones , Sciuridae
7.
Nat Commun ; 12(1): 2262, 2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33859185

RESUMEN

El Nino is a critical part of global inter-annual climate variability, and the intensity of El Nino has major implications for rainfall-induced natural hazards in many vulnerable countries. The impact of landslides triggered by rainfall is likely to be modulated by the strength of El Nino, but the nature of this connection and the places where it is most relevant remains unconstrained. Here we combine new satellite rainfall data with a global landslide exposure model to show that El Nino has far-reaching effects on landslide impacts to people and infrastructure. We find that the impact of El Nino on landslide exposure can be greater in parts of Southeast Asia and Latin America than that due to seasonal rainfall variability. These findings improve our understanding of hazard variability around the world and can assist disaster mitigation efforts on seasonal timescales.

8.
Glob Chang Biol ; 27(10): 2254-2268, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33687129

RESUMEN

Tropical mountains harbor globally significant levels of biodiversity and endemism. Climate change threatens many tropical montane species, yet little research has assessed the effects of climate change on the demographic rates of tropical species, particularly in the Afrotropics. Here, we report on the demographic rates of 21 Afrotropical bird species over 30 years in montane forests in Tanzania. We used mark-recapture analyses to model rates of population growth, recruitment, and apparent survival as functions of annual mean temperature and annual precipitation. For over one-half of focal species, decreasing population growth rates were associated with increasing temperature. Due to the trend in temperature over time, we substituted a time covariate for the temperature covariate in top-ranked population growth rate models. Temperature was a better explanatory covariate than time for 6 of the 12 species, or 29% of all focal species. Population growth rates were also lower for species found further below their elevational midpoint and for smaller-bodied species. Changes in population growth rates were more closely tied to changes in recruitment than to changes in apparent survival. There were no consistent associations between demographic rates and precipitation. This study demonstrates temperature-associated demographic impacts for 6 (29%) of 21 focal species in an Afrotropical understory bird community and highlights the need to incorporate the impacts of climate change on demographic rates into conservation planning across the tropics.


Asunto(s)
Aves , Clima Tropical , Animales , Biodiversidad , Cambio Climático , Demografía , Tanzanía , Temperatura
9.
Sci Rep ; 10(1): 19560, 2020 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-33177565

RESUMEN

The accurate recognition of multiple sclerosis (MS) lesions is challenged by the high sensitivity and imperfect specificity of MRI. To examine whether longitudinal changes in volume, surface area, 3-dimensional (3D) displacement (i.e. change in lesion position), and 3D deformation (i.e. change in lesion shape) could inform on the origin of supratentorial brain lesions, we prospectively enrolled 23 patients with MS and 11 patients with small vessel disease (SVD) and performed standardized 3-T 3D brain MRI studies. Bayesian linear mixed effects regression models were constructed to evaluate associations between changes in lesion morphology and disease state. A total of 248 MS and 157 SVD lesions were studied. Individual MS lesions demonstrated significant decreases in volume < 3.75mm3 (p = 0.04), greater shifts in 3D displacement by 23.4% with increasing duration between MRI time points (p = 0.007), and greater transitions to a more non-spherical shape (p < 0.0001). If 62.2% of lesions within a given MRI study had a calculated theoretical radius > 2.49 based on deviation from a perfect 3D sphere, a 92.7% in-sample and 91.2% out-of-sample accuracy was identified for the diagnosis of MS. Longitudinal 3D shape evolution and displacement characteristics may improve lesion classification, adding to MRI techniques aimed at improving lesion specificity.


Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Adulto , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/clasificación , Imagenología Tridimensional/clasificación , Imagenología Tridimensional/métodos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/diagnóstico por imagen , Esclerosis Múltiple/tratamiento farmacológico
10.
Mult Scler Relat Disord ; 45: 102429, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32805478

RESUMEN

OBJECTIVE: To compare the temporal changes in the 3-dimensional (3D) structure of the medulla-upper cervical spinal cord region in African American (AA) and white multiple sclerosis (MS) patients to identify early patterns of anatomical change prior to progressive symptom development. METHODS: Standardized 3-Tesla 3D brain MRI studies were performed at two time points on AA and white MS patients along with controls. Longitudinal changes in volume, surface area, tissue compliance, and surface texture measured in total and within ventral and dorsal compartments were studied. Independent regression models were constructed to evaluate differences between groups. RESULTS: Thirty-five individuals were studied, 10 AA with MS (female (F): 8; median age [IQR]=33.8 years (y) [10.9], median disease duration: 11.8y [11.3]), 20 white MS patients (F: 10; 35.6y [17.4], 7.23y [8.83], and 5 controls (F: 2, 51.8y [10.2]). Expanded Disability Status Scale scores were 0.0 at baseline and at the second MRI time point. Within the medulla-upper cervical spinal cord, AA versus white MS patients exhibited greater rates of atrophy in total (p<0.0001) and within the ventral (p<0.0001) and dorsal (p<0.0001) compartments, reduced surface area (p<0.0001), and reduced tissue compliance in the ventral (p=0.002) and dorsal (p=0.0005) compartments. The rate of change at the dorsal surface, but not the ventral surface, between MRI time points was also greater in AA relative to white MS patients (p<0.0001). CONCLUSION: Structural changes in distinct anatomical regions of the medulla-upper cervical spinal cord may be reflective of early and disproportionate neurodegeneration in AA MS as compared to whites.


Asunto(s)
Médula Cervical , Esclerosis Múltiple , Adulto , Negro o Afroamericano , Atrofia/patología , Encéfalo/patología , Médula Cervical/diagnóstico por imagen , Médula Cervical/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Médula Espinal/diagnóstico por imagen , Médula Espinal/patología
11.
J Neurol ; 267(10): 2888-2896, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32468116

RESUMEN

Multiple sclerosis (MS) diagnostic criteria are based upon clinical presentation and presence of white matter hyperintensities on two-dimensional magnetic resonance imaging (MRI) views. Such criteria, however, are prone to false-positive interpretations due to the presence of similar MRI findings in non-specific white matter disease (NSWMD) states such as migraine and microvascular disease. The coexistence of age-related changes has also been recognized in MS patients, and this comorbidity further poses a diagnostic challenge. In this study, we investigated the physiologic profiles within and around MS and NSWMD lesions and their ability to distinguish the two disease states. MS and NSWMD lesions were identified using three-dimensional (3D) T2-FLAIR images and segmented using geodesic active contouring. A dual-echo functional MRI sequence permitted near-simultaneous measurement of blood-oxygen-level-dependent signal (BOLD) and cerebral blood flow (CBF). BOLD and CBF were calculated within lesions and in 3D concentric layers surrounding each lesion. BOLD slope, an indicator of lesion metabolic capacity, was calculated as the change in BOLD from a lesion through its surrounding perimeters. We observed sequential BOLD signal reductions from the lesion towards the perimeters for MS, while no such decreases were observed for NSWMD lesions. BOLD slope was significantly lower in MS compared to NSWM lesions, suggesting decreased metabolic activity in MS lesions. Furthermore, BOLD signal within and around lesions significantly distinguished MS and NSWMD lesions. These results suggest that this technique shows promise for clinical utility in distinguishing NSWMD or MS disease states and identifying NSWMD lesions occurring in MS patients.


Asunto(s)
Leucoencefalopatías , Esclerosis Múltiple , Sustancia Blanca , Circulación Cerebrovascular , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen
12.
J Hydrometeorol ; 21(8): 1741-1759, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-34054350

RESUMEN

Many existing models that predict landslide hazards utilize ground-based sources of precipitation data. In locations where ground-based precipitation observations are limited (i.e., a vast majority of the globe), or for landslide hazard models that assess regional or global domains, satellite multisensor precipitation products offer a promising near-real-time alternative to ground-based data. NASA's global Landslide Hazard Assessment for Situational Awareness (LHASA) model uses the Integrated Multisatellite Retrievals for Global Precipitation Measurement (IMERG) product to issue hazard "nowcasts" in near-real time for areas that are currently at risk for landsliding. Satellite-based precipitation estimates, however, can contain considerable systematic bias and random error, especially over mountainous terrain and during extreme rainfall events. This study combines a precipitation error modeling framework with a probabilistic adaptation of LHASA. Compared with the routine version of LHASA, this probabilistic version correctly predicts more of the observed landslides in the study region with fewer false alarms by high hazard nowcasts. This study demonstrates that improvements in landslide hazard prediction can be achieved regardless of whether the IMERG error model is trained using abundant ground-based precipitation observations or using far fewer and more scattered observations, suggesting that the approach is viable in data-limited regions. Results emphasize the importance of accounting for both random error and systematic satellite precipitation bias. The approach provides an example of how environmental prediction models can incorporate satellite precipitation uncertainty. Other applications such as flood and drought monitoring and forecasting could likely benefit from consideration of precipitation uncertainty.

13.
Pediatr Qual Saf ; 4(4): e181, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31572883

RESUMEN

INTRODUCTION: There is a myriad of factors that can lead to temperature derangements in anesthetized children undergoing magnetic resonance imaging (MRI). Temperature abnormalities in pediatric patients are associated with increased morbidity and mortality. Although some reports have looked at this topic, to our knowledge, no studies have continuously monitored temperature throughout the MRI scan. The purpose of this study is to determine the impact of MRI on body temperature for anesthetized children undergoing MRI using continuous temperature measurement, identify patient risk factors to develop temperature abnormalities, and determine the effect of temperature derangements on perianesthetic complications. METHODS: This retrospective, single-center study evaluated 285 pediatric outpatients from January 1, 2018, to March 31, 2018, who were less than 8 years old and underwent anesthesia for an MRI scan. Temperature, postanesthesia care unit length of stay, and demographic data were collected retrospectively using chart review and data extraction from electronic medical records. Statistical analyses included unpaired t test, chi-square test, and simple and multiple linear regressions. RESULTS: Sixty-three percent (179/285) of children in our study had a median temperature less than 36°C during their MRI scan. There were no patients who had a median temperature greater than 38°C during their MRI scan. There were no identifiable patient risk factors for the development of hypothermia. Those who developed hypothermia did not have an increased rate of perianesthetic complications. CONCLUSION: MRI in anesthetized children is associated with hypothermia but does not correlate with any significant perianesthetic complications.

14.
PLoS One ; 14(7): e0218657, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31269035

RESUMEN

Robust inventories are vital for improving assessment of and response to deadly and costly landslide hazards. However, collecting landslide events in inventories is difficult at the global scale due to inconsistencies in or the absence of landslide reporting. Citizen science is a valuable opportunity for addressing some of these challenges. The new Cooperative Open Online Landslide Repository (COOLR) supplements data in a NASA-developed Global Landslide Catalog (GLC) with citizen science reports to build a more robust, publicly available global inventory. This manuscript introduces the COOLR project and its methods, evaluates the initial citizen science results from the first 13 months, and discusses future improvements to increase the global engagement with the project. The COOLR project (https://landslides.nasa.gov) contains Landslide Reporter, the first global citizen science project for landslides, and Landslide Viewer, a portal to visualize data from COOLR and other satellite and model products. From March 2018 to April 2019, 49 citizen scientists contributed 162 new landslide events to COOLR. These events spanned 37 countries in five continents. The initial results demonstrated that both expert and novice participants are contributing via Landslide Reporter. Citizen scientists are filling in data gaps through news sources in 11 different languages, in-person observations, and new landslide events occurring hundreds and thousands of kilometers away from any existing GLC data. The data is of sufficient accuracy to use in NASA susceptibility and hazard models. COOLR continues to expand as an open platform of landslide inventories with new data from citizen scientists, NASA scientists, and other landslide groups. Future work on the COOLR project will seek to increase participation and functionality of the platform as well as move towards collective post-disaster mapping.


Asunto(s)
Ciencia Ciudadana , Desastres , Deslizamientos de Tierra/prevención & control , Modelos de Riesgos Proporcionales , Monitoreo del Ambiente/métodos , Sistemas de Información Geográfica , Humanos , Deslizamientos de Tierra/estadística & datos numéricos , Medición de Riesgo , Estados Unidos , United States National Aeronautics and Space Administration
15.
J Neuroimaging ; 29(5): 605-614, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31148298

RESUMEN

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) clinical management is based upon lesion characterization from 2-dimensional (2D) magnetic resonance imaging (MRI) views. Such views fail to convey the lesion-phenotype (ie, shape and surface texture) complexity, underlying metabolic alterations, and remyelination potential. We utilized a 3-dimensional (3D) lesion phenotyping approach coupled with imaging to study physiologic profiles within and around MS lesions and their impacts on lesion phenotypes. METHODS: Lesions were identified in 3T T2 -FLAIR images and segmented using geodesic active contouring. A calibrated fMRI sequence permitted measurement of cerebral blood flow (CBF), blood-oxygen-level-dependent signal (BOLD), and cerebral metabolic rate of oxygen (CMRO2 ). These metrics were measured within lesions and surrounding tissue in concentric layers exact to the 3D-lesion shape. BOLD slope was calculated as BOLD changes from a lesion to its surrounding perimeters. White matter integrity was measured using diffusion kurtosis imaging. Associations between these metrics and 3D-lesion phenotypes were studied. RESULTS: One hundred nine lesions from 23 MS patients were analyzed. We identified a noninvasive biomarker, BOLD slope, to metabolically characterize lesions. Positive BOLD slope lesions were metabolically active with higher CMRO2 and CBF compared to negative BOLD slope or inactive lesions. Metabolically active lesions with more intact white matter integrity had more symmetrical shapes and more complex surface textures compared to inactive lesions with less intact white matter integrity. CONCLUSION: The association of lesion phenotypes with their metabolic signatures suggests the prospect for translation of such data to clinical management by providing information related to metabolic activity, lesion age, and risk for disease reactivation and self-repair. Our findings also provide a platform for disease surveillance and outcome quantification involving myelin repair therapeutics.


Asunto(s)
Esclerosis Múltiple/diagnóstico por imagen , Vaina de Mielina/patología , Remielinización/fisiología , Sustancia Blanca/diagnóstico por imagen , Adulto , Circulación Cerebrovascular/fisiología , Imagen de Difusión Tensora/métodos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/patología , Sustancia Blanca/patología
16.
Proc Biol Sci ; 285(1889)2018 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-30355706

RESUMEN

Most approaches for assessing species vulnerability to climate change have focused on direct impacts via abiotic changes rather than indirect impacts mediated by changes in species interactions. Changes in rainfall regimes may influence species interactions from the bottom-up by increasing primary productivity in arid environments, but subsequently lead to less predictable top-down effects. Our study demonstrates how the effects of an EL Niño/Southern Oscillation (ENSO)-driven rainfall pulse ricochets along a chain of interactions between marine and terrestrial food webs, leading to enhanced predation of a vulnerable marine predator on its island breeding grounds. On Santa Barbara Island, barn owls (Tyto alba) are the main predator of a nocturnal seabird, the Scripps's murrelet (Synthliboramphus scrippsi), as well as an endemic deer mouse. We followed the links between rainfall, normalized difference vegetation index and subsequent peaks in mouse and owl abundance. After the mouse population declined steeply, there was approximately 15-fold increase in the number of murrelets killed by owls. We also simulated these dynamics with a mathematical model and demonstrate that bottom-up resource pulses can lead to subsequent declines in alternative prey. Our study highlights the need for understanding how species interactions will change with shifting rainfall patterns through the effects of ENSO under global change.


Asunto(s)
Charadriiformes , Cambio Climático , El Niño Oscilación del Sur , Cadena Alimentaria , Peromyscus , Estrigiformes/fisiología , Animales , California , Conducta Predatoria , Lluvia
17.
Future Sci OA ; 4(8): FSO329, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30271616

RESUMEN

Formaldehyde is a widely used aldehyde in biomedical applications, including tissue fixation. It is this same fixative property that can result in toxicity if aldehydes are improperly discarded. A proper neutralization of aldehyde waste products can address this, thereby reducing both health and environmental toxicity concerns. In this study two commercially available products designed to neutralize formaldehyde were evaluated, including neutralization of laboratory derived tissue fixative waste. The primary selection criteria for inclusion in the study were: their ease of use (based on product instructions); the two products assert high levels of formaldehyde neutralization (below 20 ppm) relative to other neutralizing products and their lack of generation of polymeric residues that can clog drains. Both products tested were relatively easy to use and both achieved <10 ppm residual levels of formaldehyde from standard formalin and glutaraldehyde preparations used in research and clinical laboratories.

18.
J Neurooncol ; 139(3): 731-738, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29882044

RESUMEN

PURPOSE: Pseudoprogression is often indistinguishable from true tumor progression on conventional 2-dimensional (2D) MRI in glioblastoma multiforme (GBM) patients. The aim of this study was to determine the association between post-gadolinium 3-dimensional (3D) characteristics and clinical state in GBM patients. METHODS: Standardized 3D brain MRI studies were performed, and contrast enhancing portions of each tumor were segmented and analyzed, blinded to clinical state, using principal component analysis (PCA), medial axis transformation (MAT), and coverage analysis. Associations between the 3D characteristics of the post-gadolinium enhanced regions and the clinical status of patients were performed. RESULTS: A total of 15 GBM patients [male: 11 (73%); median age (range): 62 years (36-72)] with a median disease duration of 6 months (range 2-24 months) were studied cross-sectionally with 6 (40%) patients identified with tumor progression. Post-gadolinium features corresponding to the group with progressive disease exhibited a more spherical and symmetric shape relative to their stable counterparts (p = 0.005). The predictive value of a more uniformly full post-gadolinium enhanced shell to clinical progression was determined with a sensitivity of 66.7% (95% CI 29.9-92.5), specificity of 100% (54.1-100), and PPV of 100% (p = 0.028, 2-tailed Fisher's exact test). There did not appear to be an association between the thickness of the contrast enhanced shell to clinical state. CONCLUSIONS: The application of 3D technology with post-gadolinium imaging data may inform healthcare providers with new insights into disease states based on spatial, surface, and structural patterns.


Asunto(s)
Neoplasias Encefálicas/patología , Quimioradioterapia/métodos , Gadolinio/metabolismo , Glioblastoma/patología , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Glioblastoma/metabolismo , Glioblastoma/terapia , Humanos , Masculino , Persona de Mediana Edad , Pronóstico
19.
Earths Future ; Volume 6(Iss 3): 505-523, 2018 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-31709272

RESUMEN

Determining the time, location, and severity of natural disaster impacts is fundamental to formulating mitigation strategies, appropriate and timely responses, and robust recovery plans. A Landslide Hazard Assessment for Situational Awareness (LHASA) model was developed to indicate potential landslide activity in near real-time. LHASA combines satellite-based precipitation estimates with a landslide susceptibility map derived from information on slope, geology, road networks, fault zones, and forest loss. Precipitation data from the Global Precipitation Measurement (GPM) mission are used to identify rainfall conditions from the past seven days. When rainfall is considered to be extreme and susceptibility values are moderate to very high, a "nowcast" is issued to indicate the times and places where landslides are more probable. When LHASA nowcasts were evaluated with a Global Landslide Catalog, the probability of detection (POD) ranged from 8 to 60%, depending on the evaluation period, precipitation product used, and the size of the spatial and temporal window considered around each landslide point. Applications of the LHASA system are also discussed, including how LHASA is used to estimate long-term trends in potential landslide activity at a nearly global scale and how it can be used as a tool to support disaster risk assessment. LHASA is intended to provide situational awareness of landslide hazards in near real-time, providing a flexible, open source framework that can be adapted to other spatial and temporal scales based on data availability.

20.
Acad Radiol ; 25(1): 74-81, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29074334

RESUMEN

RATIONALE AND OBJECTIVES: Our research team has developed a magnetic resonance imaging (MRI)-compatible robot for long bone biopsy. The robot is intended to enable a new workflow for bone biopsy in pediatrics under MRI imaging. Our long-term objectives are to minimize trauma and eliminate radiation exposure when diagnosing children with bone cancers and bone infections. This article presents our robotic systems, phantom accuracy studies, and workflow analysis. MATERIALS AND METHODS: This section describes several aspects of our work including the envisioned clinical workflow, the MRI-compatible robot, and the experimental setup. The workflow consists of five steps and is intended to enable the entire procedure to be completed in the MRI suite. The MRI-compatible robot is MR Safe, has 3 degrees of freedom, and a remote center of motion mechanism for orienting a needle guide. The accuracy study was done in a Siemens Aera 1.5T scanner with a long bone phantom. Four targeting holes were drilled in the phantom. RESULTS: Each target was approached twice at slightly oblique angles using the robot needle guide for a total of eight attempts. A workflow analysis showed the average time for each targeting attempt was 32 minutes, including robot setup time. The average 3D targeting error was 1.39 mm with a standard deviation of 0.40 mm. All of the targets were successfully reached. CONCLUSION: The results showed the ability of the robotic system in assisting the radiologist to precisely target a bone phantom in the MRI environment. The robot system has several potential advantages for clinical application, including the ability to work at the MRI isocenter and serve as a steady and precise guide.


Asunto(s)
Huesos/patología , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética , Procedimientos Quirúrgicos Robotizados , Humanos , Modelos Biológicos , Fantasmas de Imagen , Flujo de Trabajo
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