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1.
Gigascience ; 8(11)2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31742599

RESUMO

BACKGROUND: Measurement of plant traits with precision and speed on large populations has emerged as a critical bottleneck in connecting genotype to phenotype in genetics and breeding. This bottleneck limits advancements in understanding plant genomes and the development of improved, high-yielding crop varieties. RESULTS: Here we demonstrate the application of deep learning on proximal imaging from a mobile field vehicle to directly estimate plant morphology and developmental stages in wheat under field conditions. We developed and trained a convolutional neural network with image datasets labeled from expert visual scores and used this "breeder-trained" network to classify wheat morphology and developmental stages. For both morphological (awned) and phenological (flowering time) traits, we demonstrate high heritability and very high accuracy against the "ground-truth" values from visual scoring. Using the traits predicted by the network, we tested genotype-to-phenotype association using the deep learning phenotypes and uncovered novel epistatic interactions for flowering time. Enabled by the time-series high-throughput phenotyping, we describe a new phenotype as the rate of flowering and show heritable genetic control for this trait. CONCLUSIONS: We demonstrated a field-based high-throughput phenotyping approach using deep learning that can directly measure morphological and developmental phenotypes in genetic populations from field-based imaging. The deep learning approach presented here gives a conceptual advancement in high-throughput plant phenotyping because it can potentially estimate any trait in any plant species for which the combination of breeder scores and high-resolution images can be obtained, capturing the expert knowledge from breeders, geneticists, pathologists, and physiologists to train the networks.

2.
J Biomech Eng ; 141(1)2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30267039

RESUMO

Quantifying dynamic strain fields from time-resolved volumetric medical imaging and microscopy stacks is a pressing need for radiology and mechanobiology. A critical limitation of all existing techniques is regularization: because these volumetric images are inherently noisy, the current strain mapping techniques must impose either displacement regularization and smoothing that sacrifices spatial resolution, or material property assumptions that presuppose a material model, as in hyperelastic warping. Here, we present, validate, and apply the first three-dimensional (3D) method for estimating mechanical strain directly from raw 3D image stacks without either regularization or assumptions about material behavior. We apply the method to high-frequency ultrasound images of mouse hearts to diagnose myocardial infarction. We also apply the method to present the first ever in vivo quantification of elevated strain fields in the heart wall associated with the insertion of the chordae tendinae. The method shows promise for broad application to dynamic medical imaging modalities, including high-frequency ultrasound, tagged magnetic resonance imaging, and confocal fluorescence microscopy.

3.
Clin Pharmacol Ther ; 104(3): 432-434, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30117148

RESUMO

Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other possible drug-related problems.1 While current models of pharmacovigilance, with their tools and methodologies, were developed for prescription drugs, safety surveillance is just as important for over-the-counter health products such as dietary supplements. The practice of pharmacovigilance is challenging in itself; however, there are unique challenges associated with dietary supplements.2.

4.
J Child Neurol ; 32(3): 301-307, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28193112

RESUMO

We describe the presenting features and long-term outcome of an unusual cluster of pediatric acute flaccid paralysis cases that occurred in Canada during the 2014 enterovirus D68 outbreak. Children (n = 25; median age 7.8 years) presenting to Canadian centers between July 1 and October 31, 2014, and who met diagnostic criteria for acute flaccid paralysis were evaluated retrospectively. The predominant presenting features included prodromal respiratory illness (n = 22), cerebrospinal fluid lymphocytic pleocytosis (n = 18), pain in neck/back (n = 14) and extremities (n = 10), bowel/bladder dysfunction (n = 9), focal central gray matter lesions found in all regions of the spinal cord within the cohort (n = 16), brain stem lesions (n = 8), and bulbar symptoms (n = 5). Enterovirus D68 was detectable in nasopharyngeal specimens (n = 7) but not in cerebrospinal fluid. Acute therapies (corticosteroids, intravenous immunoglobulins, plasmapheresis) were well tolerated with few side effects. Fourteen of 16 patients who were followed beyond 12 months post onset had neurologic deficits but showed ongoing clinical improvement and motor recovery.


Assuntos
Encéfalo/diagnóstico por imagem , Enterovirus Humano D , Infecções por Enterovirus/complicações , Paraplegia/terapia , Potenciais de Ação/fisiologia , Adolescente , Corticosteroides/uso terapêutico , Canadá , Criança , Pré-Escolar , Eletromiografia , Infecções por Enterovirus/fisiopatologia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Masculino , Músculo Esquelético/fisiopatologia , Condução Nervosa/fisiologia , Paraplegia/diagnóstico por imagem , Paraplegia/tratamento farmacológico , Paraplegia/virologia , Plasmaferese , Estudos Retrospectivos , Resultado do Tratamento
5.
Vaccine ; 34(49): 5993-5997, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27751641

RESUMO

Immunization in pregnancy provides a promising contribution to globally reducing neonatal and under-five childhood mortality and morbidity. Thorough assessment of benefits and risks for the primarily healthy pregnant women and their unborn babies is required. The GAIA project was formed in response to the call of the World Health Organization for a globally concerted approach to actively monitor the safety of vaccines and immunization in pregnancy programs. GAIA aims to improve the quality of outcome data from clinical vaccine trials in pregnant women with a specific focus on the needs and requirements for safety monitoring in LMIC. In the first year of the project, a large and functional network of experts was created. The first outputs include a guidance document for clinical trials of immunization in pregnancy, a basic data collection guide, ten case definitions of key obstetric and neonatal health outcomes, an ontology of key terms and a map of pertinent disease codes. The GAIA Network is designed as an open and growing forum for professionals sharing the GAIA vision and aim. Based on the initial achievements, tools and services are developed to support investigators and strengthen immunization in pregnancy programs with specific focus on LMIC.


Assuntos
Saúde Global , Imunização/efeitos adversos , Gravidez , Vacinas/efeitos adversos , Ensaios Clínicos como Assunto , Feminino , Humanos , Vacinas/administração & dosagem , Organização Mundial da Saúde
6.
Front Public Health ; 4: 97, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27242989

RESUMO

INTRODUCTION: Active transportation opportunities and infrastructure are an important component of a community's design, livability, and health. Features of the built environment influence active transportation, but objective study of the natural experiment effects of built environment improvements on active transportation is challenging. The purpose of this study was to develop and present a novel method of active transportation research using webcams and crowdsourcing, and to determine if crosswalk enhancement was associated with changes in active transportation rates, including across a variety of weather conditions. METHODS: The 20,529 publicly available webcam images from two street intersections in Washington, DC, USA were used to examine the impact of an improved crosswalk on active transportation. A crowdsource, Amazon Mechanical Turk, annotated image data. Temperature data were collected from the National Oceanic and Atmospheric Administration, and precipitation data were annotated from images by trained research assistants. RESULTS: Summary analyses demonstrated slight, bi-directional differences in the percent of images with pedestrians and bicyclists captured before and after the enhancement of the crosswalks. Chi-square analyses revealed these changes were not significant. In general, pedestrian presence increased in images captured during moderate temperatures compared to images captured during hot or cold temperatures. Chi-square analyses indicated the crosswalk improvement may have encouraged walking and biking in uncomfortable outdoor conditions (P < 0.5). CONCLUSION: The methods employed provide an objective, cost-effective alternative to traditional means of examining the effects of built environment changes on active transportation. The use of webcams to collect active transportation data has applications for community policymakers, planners, and health professionals. Future research will work to validate this method in a variety of settings as well as across different built environment and community policy initiatives.

7.
Vaccine ; 34(29): 3342-9, 2016 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-27195758

RESUMO

In 1999, the Global Advisory Committee on Vaccine Safety (GACVS) was established by the World Health Organization (WHO) to provide independent scientific advice on issues relating to the safety of vaccines and immunization. Fifteen years onward, we conducted a multi-faceted review to evaluate the impact, reach and challenges facing GACVS, including the role GACVS plays in informing global, regional and WHO member state vaccine policy. The methods included measures of organizational structure, citation impact, themes approached, and a discussion by previous and current members to evaluate past, present and future challenges. Given the increasing range of data sources and the deployment of many new vaccines, the Committee is facing the complex task of identifying the best available evidence for recommendations on vaccine safety. To help meet the increased demand for public transparency in decision making, GACVS-structured methodology for evidence-based decisions is evolving. GACVS also promotes best practices and capacity building for timely and accurate risk assessment; risk communications; outreach to help countries maintain and, if needed, rebuild public trust in vaccines; and advocacy for bridging the major gaps in vaccine safety capacity globally.


Assuntos
Comitês Consultivos/organização & administração , Qualidade de Produtos para o Consumidor , Vacinas/normas , Política de Saúde , Humanos , Organização Mundial da Saúde
8.
Proc Natl Acad Sci U S A ; 112(51): E7148-54, 2015 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-26644583

RESUMO

Short-term fasting protects mice from lethal doses of chemotherapy through undetermined mechanisms. Herein, we demonstrate that fasting preserves small intestinal (SI) architecture by maintaining SI stem cell viability and SI barrier function following exposure to high-dose etoposide. Nearly all SI stem cells were lost in fed mice, whereas fasting promoted sufficient SI stem cell survival to preserve SI integrity after etoposide treatment. Lineage tracing demonstrated that multiple SI stem cell populations, marked by Lgr5, Bmi1, or HopX expression, contributed to fasting-induced survival. DNA repair and DNA damage response genes were elevated in SI stem/progenitor cells of fasted etoposide-treated mice, which importantly correlated with faster resolution of DNA double-strand breaks and less apoptosis. Thus, fasting preserved SI stem cell viability as well as SI architecture and barrier function suggesting that fasting may reduce host toxicity in patients undergoing dose intensive chemotherapy.


Assuntos
Dano ao DNA , Jejum/metabolismo , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestino Delgado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Células-Tronco/patologia
10.
Vaccine ; 32(52): 7057-64, 2014 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-25285883

RESUMO

Vaccine-preventable infectious diseases are responsible for significant maternal, neonatal, and young infant morbidity and mortality. While there is emerging scientific evidence, as well as theoretical considerations, indicating that certain vaccines are safe for pregnant women and fetuses, policy formulation is challenging because of perceived potential risks to the fetus. This report presents an overview of available evidence on pregnant women vaccination safety monitoring in pregnant women, from both published literature and ongoing surveillance programs. Safety data were reviewed for vaccines against diseases which increase morbidity in pregnant women, their fetus or infant as well as vaccines which are used in mass vaccination campaigns against diseases. They include inactivated seasonal and pandemic influenza, mono- and combined meningococcal polysaccharide and conjugated vaccines, tetanus toxoid and acellular pertussis combination vaccines, as well as monovalent or combined rubella, oral poliomyelitis virus and yellow fever vaccines. No evidence of adverse pregnancy outcomes has been identified from immunization of pregnant women with these vaccines.


Assuntos
Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/efeitos adversos , Vacinação/efeitos adversos , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Feminino , Humanos , Gravidez , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos
11.
J R Soc Interface ; 11(100): 20140685, 2014 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-25165601

RESUMO

When mechanical factors underlie growth, development, disease or healing, they often function through local regions of tissue where deformation is highly concentrated. Current optical techniques to estimate deformation can lack precision and accuracy in such regions due to challenges in distinguishing a region of concentrated deformation from an error in displacement tracking. Here, we present a simple and general technique for improving the accuracy and precision of strain estimation and an associated technique for distinguishing a concentrated deformation from a tracking error. The strain estimation technique improves accuracy relative to other state-of-the-art algorithms by directly estimating strain fields without first estimating displacements, resulting in a very simple method and low computational cost. The technique for identifying local elevation of strain enables for the first time the successful identification of the onset and consequences of local strain concentrating features such as cracks and tears in a highly strained tissue. We apply these new techniques to demonstrate a novel hypothesis in prenatal wound healing. More generally, the analytical methods we have developed provide a simple tool for quantifying the appearance and magnitude of localized deformation from a series of digital images across a broad range of disciplines.


Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Modelos Biológicos
12.
Proc Natl Acad Sci U S A ; 111(12): 4602-7, 2014 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-24616527

RESUMO

Whether measured by MRI or direct cortical physiology, infraslow rhythms have defined state invariant cortical networks. The time scales of this functional architecture, however, are unlikely to be able to accommodate the more rapid cortical dynamics necessary for an active cognitive task. Using invasively monitored epileptic patients as a research model, we tested the hypothesis that faster frequencies would spectrally bind regions of cortex as a transient mechanism to enable fast network interactions during the performance of a simple hear-and-repeat speech task. We term these short-lived spectrally covariant networks functional spectral networks (FSNs). We evaluated whether spectrally covariant regions of cortex, which were unique in their spectral signatures, provided a higher degree of task-related information than any single site showing more classic physiologic responses (i.e., single-site amplitude modulation). Taken together, our results showing that FSNs are a more sensitive measure of task-related brain activation and are better able to discern phonemic content strongly support the concept of spectrally encoded interactions in cortex. Moreover, these findings that specific linguistic information is represented in FSNs that have broad anatomic topographies support a more distributed model of cortical processing.


Assuntos
Córtex Cerebral/fisiologia , Eletroencefalografia , Humanos , Imagem por Ressonância Magnética
13.
IEEE Trans Pattern Anal Mach Intell ; 35(10): 2526-38, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23969394

RESUMO

We describe algorithms that use cloud shadows as a form of stochastically structured light to support 3D scene geometry estimation. Taking video captured from a static outdoor camera as input, we use the relationship of the time series of intensity values between pairs of pixels as the primary input to our algorithms. We describe two cues that relate the 3D distance between a pair of points to the pair of intensity time series. The first cue results from the fact that two pixels that are nearby in the world are more likely to be under a cloud at the same time than two distant points. We describe methods for using this cue to estimate focal length and scene structure. The second cue is based on the motion of cloud shadows across the scene; this cue results in a set of linear constraints on scene structure. These constraints have an inherent ambiguity, which we show how to overcome by combining the cloud motion cue with the spatial cue. We evaluate our method on several time lapses of real outdoor scenes.


Assuntos
Algoritmos , Inteligência Artificial , Atmosfera , Interpretação de Imagem Assistida por Computador/métodos , Imagem Tridimensional/métodos , Reconhecimento Automatizado de Padrão/métodos , Imagem com Lapso de Tempo/métodos , Calibragem , Aumento da Imagem/métodos , Modelos Biológicos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
15.
Nat Immunol ; 14(1): 41-51, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23179077

RESUMO

Coordinated navigation within tissues is essential for cells of the innate immune system to reach the sites of inflammatory processes, but the signals involved are incompletely understood. Here we demonstrate that NG2(+) pericytes controlled the pattern and efficacy of the interstitial migration of leukocytes in vivo. In response to inflammatory mediators, pericytes upregulated expression of the adhesion molecule ICAM-1 and released the chemoattractant MIF. Arteriolar and capillary pericytes attracted and interacted with myeloid leukocytes after extravasating from postcapillary venules, 'instructing' them with pattern-recognition and motility programs. Inhibition of MIF neutralized the migratory cues provided to myeloid leukocytes by NG2(+) pericytes. Hence, our results identify a previously unknown role for NG2(+) pericytes as an active component of innate immune responses, which supports the immunosurveillance and effector function of extravasated neutrophils and macrophages.


Assuntos
Molécula 1 de Adesão Intercelular/metabolismo , Oxirredutases Intramoleculares/metabolismo , Leucócitos/imunologia , Fatores Inibidores da Migração de Macrófagos/metabolismo , Pericitos/imunologia , Receptores de Reconhecimento de Padrão/imunologia , Anticorpos Bloqueadores/farmacologia , Arteríolas/imunologia , Capilares/imunologia , Comunicação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Células Cultivadas , Humanos , Imunidade Inata , Mediadores da Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/genética , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/imunologia , Leucócitos/efeitos dos fármacos , Fatores Inibidores da Migração de Macrófagos/genética , Fatores Inibidores da Migração de Macrófagos/imunologia , Ativação de Neutrófilo/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Vênulas/imunologia
16.
PLoS One ; 7(12): e45512, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23300512

RESUMO

Characterizing how cells in three-dimensional (3D) environments or natural tissues respond to biophysical stimuli is a longstanding challenge in biology and tissue engineering. We demonstrate a strategy to monitor morphological and mechanical responses of contractile fibroblasts in a 3D environment. Cells responded to stretch through specific, cell-wide mechanisms involving staged retraction and reinforcement. Retraction responses occurred for all orientations of stress fibers and cellular protrusions relative to the stretch direction, while reinforcement responses, including extension of cellular processes and stress fiber formation, occurred predominantly in the stretch direction. A previously unreported role of F-actin clumps was observed, with clumps possibly acting as F-actin reservoirs for retraction and reinforcement responses during stretch. Responses were consistent with a model of cellular sensitivity to local physical cues. These findings suggest mechanisms for global actin cytoskeleton remodeling in non-muscle cells and provide insight into cellular responses important in pathologies such as fibrosis and hypertension.


Assuntos
Actinas/metabolismo , Citoesqueleto/fisiologia , Fibroblastos/citologia , Modelos Teóricos , Fibras de Estresse/química , Estresse Mecânico , Animais , Cálcio/metabolismo , Técnicas de Cultura de Células , Células Cultivadas , Embrião de Galinha , Fibroblastos/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo
17.
PLoS One ; 6(7): e22063, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21811560

RESUMO

Non-destructive measurement of acceleration-induced displacement fields within a closed object is a fundamental challenge. Inferences of how the brain deforms following skull impact have thus relied largely on indirect estimates and course-resolution cadaver studies. We developed a magnetic resonance technique to quantitatively identify the modes of displacement of an accelerating soft object relative to an object enclosing it, and applied it to study acceleration-induced brain deformation in human volunteers. We show that, contrary to the prevailing hypotheses of the field, the dominant mode of interaction between the brain and skull in mild head acceleration is one of sliding arrested by meninges.


Assuntos
Encéfalo/anatomia & histologia , Imagem por Ressonância Magnética/métodos , Análise de Componente Principal , Calibragem , Elasticidade , Gelatina , Humanos , Modelos Biológicos , Imagens de Fantasmas , Vibração , Viscosidade
18.
Emerg Infect Dis ; 16(12): 1986-9, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21122239

RESUMO

We conducted a case-control study to describe the clinical and epidemiologic characteristics of an outbreak of pandemic (H1N1) 2009 at a Canadian military cadet training center. We found that asthma and obesity confer greater risk for infection. Viral shedding was detected by PCR up to 18 days after symptom onset.


Assuntos
Surtos de Doenças , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Militares , Adolescente , Adulto , Asma/epidemiologia , Canadá/epidemiologia , Estudos de Casos e Controles , Tosse/diagnóstico , Tosse/epidemiologia , Feminino , Febre/diagnóstico , Febre/epidemiologia , Humanos , Masculino , Obesidade/epidemiologia , Fatores de Risco , Eliminação de Partículas Virais
19.
Proc Natl Acad Sci U S A ; 107(42): 18073-8, 2010 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-20923880

RESUMO

Immune-mediated pulmonary diseases are a significant public health concern. Analysis of leukocyte behavior in the lung is essential for understanding cellular mechanisms that contribute to normal and diseased states. Here, we used two-photon imaging to study neutrophil extravasation from pulmonary vessels and subsequent interstitial migration. We found that the lungs contained a significant pool of tissue-resident neutrophils in the steady state. In response to inflammation produced by bacterial challenge or transplant-mediated, ischemia-reperfusion injury, neutrophils were rapidly recruited from the circulation and patrolled the interstitium and airspaces of the lung. Motile neutrophils often aggregated in dynamic clusters that formed and dispersed over tens of minutes. These clusters were associated with CD115(+) F4/80(+) Ly6C(+) cells that had recently entered the lung. The depletion of blood monocytes with clodronate liposomes reduced neutrophil clustering in the lung, but acted by inhibiting neutrophil transendothelial migration upstream of interstitial migration. Our results suggest that a subset of monocytes serve as key regulators of neutrophil extravasation in the lung and may be an attractive target for the treatment of inflammatory pulmonary diseases.


Assuntos
Pulmão/citologia , Microscopia/métodos , Monócitos/citologia , Neutrófilos/citologia , Animais , Quimiotaxia de Leucócito , Camundongos , Fótons
20.
Methods Enzymol ; 461: 349-78, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19480927

RESUMO

Two-photon (2P) microscopy is a high-resolution imaging technique that was initially applied by neurobiologists and developmental cell biologists but has subsequently been broadly adapted by immunologists. The value of 2P microscopy is that it affords an unparalleled view of single-cell spatiotemporal dynamics deep within intact tissues and organs. As the technology develops and new transgenic mice and fluorescent probes become available, 2P microscopy will serve as an increasingly valuable tool for assessing cell function and probing molecular mechanisms. Here we discuss the technical aspects related to 2P microscope design, explain in detail various tissue imaging preparations, and walk the reader through the often daunting process of analyzing multidimensional data sets and presenting the experimental results.


Assuntos
Células/metabolismo , Microscopia/instrumentação , Microscopia/métodos , Animais , Humanos , Camundongos , Microscopia de Fluorescência por Excitação Multifotônica/instrumentação , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Software
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