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2.
Nature ; 582(7813): 525-529, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32581382

RESUMO

Oceanic lithosphere carries volatiles, notably water, into the mantle through subduction at convergent plate boundaries. This subducted water exercises control on the production of magma, earthquakes, formation of continental crust and mineral resources. Identifying different potential fluid sources (sediments, crust and mantle lithosphere) and tracing fluids from their release to the surface has proved challenging1. Atlantic subduction zones are a valuable endmember when studying this deep water cycle because hydration in Atlantic lithosphere, produced by slow spreading, is expected to be highly non-uniform2. Here, as part of a multi-disciplinary project in the Lesser Antilles volcanic arc3, we studied boron trace element and isotopic fingerprints of melt inclusions. These reveal that serpentine-that is, hydrated mantle rather than crust or sediments-is a dominant supplier of subducted water to the central arc. This serpentine is most likely to reside in a set of major fracture zones subducted beneath the central arc over approximately the past ten million years. The current dehydration of these fracture zones coincides with the current locations of the highest rates of earthquakes and prominent low shear velocities, whereas the preceding history of dehydration is consistent with the locations of higher volcanic productivity and thicker arc crust. These combined geochemical and geophysical data indicate that the structure and hydration of the subducted plate are directly connected to the evolution of the arc and its associated seismic and volcanic hazards.

3.
J Hepatol ; 71(6): 1229-1236, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31470068

RESUMO

BACKGROUND & AIMS: Cancer is a major cause of death in patients with non-alcoholic fatty liver disease (NAFLD). Obesity is a risk factor for cancers; however, the role of NAFLD in this association is unknown. We investigated the effect of NAFLD versus obesity on incident cancers. METHODS: We identified all incident cases of NAFLD in a US population between 1997-2016. Individuals with NAFLD were matched by age and sex to referent individuals from the same population (1:3) on the index diagnosis date. We ascertained the incidence of cancer after index date until death, loss to follow-up or study end. NAFLD and cancer were defined using a code-based algorithm with high validity and tested by medical record review. The association between NAFLD or obesity and cancer risk was examined using Poisson regression. RESULTS: A total of 4,722 individuals with NAFLD (median age 54, 46% male) and 14,441 age- and sex-matched referent individuals were followed for a median of 8 (range 1-21) years, during which 2,224 incident cancers occurred. NAFLD was associated with 90% higher risk of malignancy: incidence rate ratio (IRR) = 1.9 (95% CI 1.3-2.7). The highest risk increase was noted in liver cancer, IRR = 2.8 (95% CI 1.6-5.1), followed by uterine IRR = 2.3 (95% CI 1.4-4.1), stomach IRR = 2.3 (95% CI 1.3-4.1), pancreas IRR = 2.0 (95% CI 1.2-3.3) and colon cancer IRR = 1.8 (95% CI 1.1-2.8). In reference to non-obese controls, NAFLD was associated with a higher risk of incident cancers (IRR = 2.0, 95% CI 1.5-2.9), while obesity alone was not (IRR = 1.0, 95% CI 0.8-1.4). CONCLUSIONS: NAFLD was associated with increased cancer risk, particularity of gastrointestinal types. In the absence of NAFLD, the association between obesity and cancer risk is small, suggesting that NAFLD may be a mediator of the obesity-cancer association. LAY SUMMARY: We studied the incidence of malignancies in a community cohort of adults with non-alcoholic fatty liver disease (NAFLD) in reference to age- and sex-matched adults without NAFLD. After 21 years of longitudinal follow-up, NAFLD was associated with a nearly 2-fold increase in the risk of developing cancers, predominantly of the liver, gastrointestinal tract and uterus. The association with increased cancer risk was stronger in NAFLD than obesity.


Assuntos
Neoplasias do Sistema Digestório , Neoplasias , Hepatopatia Gordurosa não Alcoólica , Obesidade , Estudos de Coortes , Neoplasias do Sistema Digestório/epidemiologia , Neoplasias do Sistema Digestório/patologia , Feminino , Seguimentos , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias/classificação , Neoplasias/epidemiologia , Neoplasias/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade/diagnóstico , Obesidade/epidemiologia , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Estados Unidos/epidemiologia
4.
J Stroke Cerebrovasc Dis ; 26(4): e72-e73, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28236596

RESUMO

We report a case of a 58-year-old Hispanic man who developed ascending paraparesis over several weeks secondary to recurrent hemorrhages and resulting in spinal cord ischemia from a low thoracic spinal cord cavernous malformation. The patient's deterioration was attributed to recurrent hemorrhage of a thoracic intramedullary cavernous malformation at T11 resulting in vascular congestion and spinal cord ischemia. The patient was found to have a heterozygous mutation on exon 13 of gene KRIT1, which was consistent with autosomal dominant familial cerebral cavernous malformations. Expedited surgical intervention potentially could have prevented this patient's progressive paraplegia.


Assuntos
Vias Aferentes/patologia , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Infarto/complicações , Medula Espinal/patologia , Vias Aferentes/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Humanos , Infarto/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Medula Espinal/diagnóstico por imagem
5.
Science ; 385(6714): 1196-1205, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39264997

RESUMO

Climate change is increasingly predisposing polar regions to large landslides. Tsunamigenic landslides have occurred recently in Greenland (Kalaallit Nunaat), but none have been reported from the eastern fjords. In September 2023, we detected the start of a 9-day-long, global 10.88-millihertz (92-second) monochromatic very-long-period (VLP) seismic signal, originating from East Greenland. In this study, we demonstrate how this event started with a glacial thinning-induced rock-ice avalanche of 25 × 106 cubic meters plunging into Dickson Fjord, triggering a 200-meter-high tsunami. Simulations show that the tsunami stabilized into a 7-meter-high long-duration seiche with a frequency (11.45 millihertz) and slow amplitude decay that were nearly identical to the seismic signal. An oscillating, fjord-transverse single force with a maximum amplitude of 5 × 1011 newtons reproduced the seismic amplitudes and their radiation pattern relative to the fjord, demonstrating how a seiche directly caused the 9-day-long seismic signal. Our findings highlight how climate change is causing cascading, hazardous feedbacks between the cryosphere, hydrosphere, and lithosphere.

6.
Hum Brain Mapp ; 34(3): 519-29, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22102212

RESUMO

TRACK-HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3-Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross-sectional data from this large well-characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene-positive subjects (120 PreHD and 119 early HD) from the TRACK-HD study were included. Using voxel-based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, metronome tapping, and gait); oculomotor [anti-saccade error rate (ASE)]; cognition (negative emotion recognition, spot the change and the University of Pennsylvania smell identification test) and neuropsychiatric measures (apathy, affect and irritability). After adjusting for estimated disease severity, regionally specific associations between structural loss and task performance were found (familywise error corrected, P < 0.05); impairment in tongue force, metronome tapping and ASE were all associated with striatal loss. Additionally, tongue force deficits and ASE were associated with volume reduction in the occipital lobe. Impaired recognition of negative emotions was associated with volumetric reductions in the precuneus and cuneus. Our study reveals specific associations between atrophy and decline in a range of clinical modalities, demonstrating the utility of VBM correlation analysis for investigating these relationships in HD.


Assuntos
Mapeamento Encefálico , Encéfalo/patologia , Doença de Huntington/complicações , Doença de Huntington/patologia , Adulto , Atrofia/etiologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/patologia , Estudos de Coortes , Progressão da Doença , Feminino , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/patologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Transtornos da Motilidade Ocular/etiologia , Transtornos da Motilidade Ocular/patologia , Transtornos Psicomotores/etiologia , Transtornos Psicomotores/patologia , Língua/fisiopatologia
7.
Data Brief ; 50: 109616, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37808541

RESUMO

This article describes a dataset with 464 push test results for studs welded within the ribs of profiled steel decking transverse to the supporting beams. The experimental data were collected from 30 publications dated from 1980 to 2017. The dataset presents the measured shear resistance per stud, with over 20 nominal or measured parameters, including: the properties of studs, deck, and concrete; the number of studs within a concrete rib; and the dimensions determining stud position within the concrete rib. This article presents and discusses the statistical parameters of the dataset variables, their distributions, and correlations. The dataset supports the identification of the key design variables that affect the stud shear resistance. It also provides information for evaluating the accuracy and reliability of existing design models, and may be used to form the basis for developing new predictive models.

8.
Sci Adv ; 9(5): eadd2143, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36724230

RESUMO

Volatiles expelled from subducted plates promote melting of the overlying warm mantle, feeding arc volcanism. However, debates continue over the factors controlling melt generation and transport, and how these determine the placement of volcanoes. To broaden our synoptic view of these fundamental mantle wedge processes, we image seismic attenuation beneath the Lesser Antilles arc, an end-member system that slowly subducts old, tectonized lithosphere. Punctuated anomalies with high ratios of bulk-to-shear attenuation (Qκ-1/Qµ-1 > 0.6) and VP/VS (>1.83) lie 40 km above the slab, representing expelled fluids that are retained in a cold boundary layer, transporting fluids toward the back-arc. The strongest attenuation (1000/QS ~ 20), characterizing melt in warm mantle, lies beneath the back-arc, revealing how back-arc mantle feeds arc volcanoes. Melt ponds under the upper plate and percolates toward the arc along structures from earlier back-arc spreading, demonstrating how slab dehydration, upper-plate properties, past tectonics, and resulting melt pathways collectively condition volcanism.

9.
Hum Brain Mapp ; 33(1): 203-12, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21264990

RESUMO

OBJECTIVES: To investigate the function-structure relationship of white matter within different stages of Huntington's disease (HD) using diffusion tensor imaging (DTI). EXPERIMENTAL DESIGN: From the TRACK-HD study, an early stage HD group and a premanifest gene carrier group (PMGC) were age-matched to two healthy control groups; all underwent 3-T MRI scanning of the brain. Region of interest (ROI) segmentation of the corpus callosum, caudate nucleus, thalamus, prefrontal cortex, and sensorimotor cortex was applied, and the apparent fiber pathways of these regions were analyzed. Functional measures of motor, oculomotor, cognition, and behavior were correlated to DTI measures. PRINCIPLE OBSERVATIONS: In PMGC versus controls, higher apparent diffusion coefficient (ADC) was seen in white matter pathways of the sensorimotor cortex (P < 0.01) and in the ROI of corpus callosum (P < 0.017). In early HD, fiber tract analysis showed higher ADC in pathways of the corpus callosum, thalamus, sensorimotor, and prefrontal region (P < 0.01). ROI analysis showed higher diffusivity in the corpus callosum and caudate nucleus (P < 0.017). Motor, oculomotor, cognition, and probability of onset within 2 and 5 years, correlated well with ADC measures of the corpus callosum (P < 0.01 - P < 0.005), sensorimotor (P < 0.01 - P < 0.005), and prefrontal region (P < 0.01). CONCLUSIONS: Disturbances in the white matter connections of the sensorimotor cortex can be demonstrated not only in manifest HD but also in premanifest gene carriers. Connectivity measures are well related to clinical functioning. DTI measures can be regarded as a potential biomarker for HD, due to their ability to objectify changes in brain structures and their role within brain networks.


Assuntos
Doença de Huntington/patologia , Córtex Motor/patologia , Fibras Nervosas Mielinizadas/patologia , Adulto , Encéfalo/patologia , Mapeamento Encefálico , Imagem de Tensor de Difusão , Progressão da Doença , Feminino , Humanos , Doença de Huntington/psicologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
10.
Stereotact Funct Neurosurg ; 90(2): 124-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22398800

RESUMO

We report a case of induced oscillopsia caused by deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN). Recent reports have described involuntary oscillopsia during DBS of the PPN that patients have described as trembling vision. Here we substantiate this observation using infra-red eye tracking. It has been suggested that this phenomenon might be used as an indicator of accurate targeting of the PPN with DBS. Our observations suggest that this phenomenon may not be related to a constricted anatomical structure and therefore such practise may be unwise. Scrutiny has led us to believe that the oscillopsia in our patient is not caused by direct stimulation of the oculomotor nerve as suggested in a previous report, but by stimulation of fibres in the uncinate fasciculus of the cerebellum and the superior cerebellar peduncle, which in turn stimulate the saccadic pre-motor neurones in the brainstem.


Assuntos
Estimulação Encefálica Profunda/efeitos adversos , Transtornos da Motilidade Ocular/etiologia , Doença de Parkinson/terapia , Núcleo Tegmental Pedunculopontino/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos da Motilidade Ocular/fisiopatologia , Doença de Parkinson/fisiopatologia
11.
Nat Commun ; 12(1): 4211, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244511

RESUMO

The margins of the Caribbean and associated hazards and resources have been shaped by a poorly understood history of subduction. Using new data, we improve teleseismic P-wave imaging of the eastern Caribbean upper mantle and compare identified subducted-plate fragments with trench locations predicted from plate reconstruction. This shows that material at 700-1200 km depth below South America derives from 90-115 Myr old westward subduction, initiated prior to Caribbean Large-Igneous-Province volcanism. At shallower depths, an accumulation of subducted material is attributed to Great Arc of the Caribbean subduction as it evolved over the past 70 Ma. We interpret gaps in these subducted-plate anomalies as: a plate window and tear along the subducted Proto-Caribbean ridge; tearing along subducted fracture zones, and subduction of a volatile-rich boundary between Proto-Caribbean and Atlantic domains. Phases of back-arc spreading and arc jumps correlate with changes in age, and hence buoyancy, of the subducting plate.

12.
J Vis ; 10(14)2010 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-21191130

RESUMO

Visual prostheses for the restoration of functional vision are currently under development. To guide prosthesis research and allow for an accurate prognosis of functional gain, simulating the experience of a retinal prosthesis in healthy individuals is desirable. Current simulation paradigms lack crucial aspects of the prosthetic experience such as realistic head- and eye-position-dependent image presentation. We developed a simulation paradigm that used a head-mounted camera and eye tracker to lock the simulation to the point of fixation. We evaluated visual acuity, object recognition and manipulation, and wayfinding under simulated prosthetic vision. We explored three ways of optimizing the information content of the prosthetic visual image: Full-Field representation (wide visual angle, low sampling frequency), Region of Interest (ROI; narrow visible angle, high sampling frequency), and Fisheye (high sampling frequency in the center, progressively lower resolution toward the edges). Full-Field representation facilitated visual search and navigation, whereas ROI improved visual acuity. The Fisheye representation, designed to incorporate the benefits of both Full-Field representation and ROI, performed similarly to ROI with subjects unable to capitalize on the peripheral data. The observation that different image representation conditions prove advantageous for different tasks should be taken into account in the process of designing and testing new visual prosthesis prototypes.


Assuntos
Simulação por Computador , Estimulação Luminosa/métodos , Baixa Visão/fisiopatologia , Baixa Visão/terapia , Próteses Visuais , Movimentos Oculares/fisiologia , Expressão Facial , Feminino , Percepção de Forma/fisiologia , Jogos Experimentais , Humanos , Masculino , Fosfenos/fisiologia , Desenho de Prótese , Psicofísica , Software , Percepção Espacial/fisiologia , Acuidade Visual/fisiologia
13.
Science ; 369(6509): 1338-1343, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32703907

RESUMO

Human activity causes vibrations that propagate into the ground as high-frequency seismic waves. Measures to mitigate the coronavirus disease 2019 (COVID-19) pandemic caused widespread changes in human activity, leading to a months-long reduction in seismic noise of up to 50%. The 2020 seismic noise quiet period is the longest and most prominent global anthropogenic seismic noise reduction on record. Although the reduction is strongest at surface seismometers in populated areas, this seismic quiescence extends for many kilometers radially and hundreds of meters in depth. This quiet period provides an opportunity to detect subtle signals from subsurface seismic sources that would have been concealed in noisier times and to benchmark sources of anthropogenic noise. A strong correlation between seismic noise and independent measurements of human mobility suggests that seismology provides an absolute, real-time estimate of human activities.


Assuntos
Atividades Cotidianas , Infecções por Coronavirus/epidemiologia , Ruído , Pneumonia Viral/epidemiologia , COVID-19 , Humanos , Pandemias , Quarentena
14.
Lancet Neurol ; 8(9): 791-801, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19646924

RESUMO

BACKGROUND: Huntington's disease (HD) is an autosomal dominant, fully penetrant, neurodegenerative disease that most commonly affects adults in mid-life. Our aim was to identify sensitive and reliable biomarkers in premanifest carriers of mutated HTT and in individuals with early HD that could provide essential methodology for the assessment of therapeutic interventions. METHODS: This multicentre study uses an extensive battery of novel assessments, including multi-site 3T MRI, clinical, cognitive, quantitative motor, oculomotor, and neuropsychiatric measures. Blinded analyses were done on the baseline cross-sectional data from 366 individuals: 123 controls, 120 premanifest (pre-HD) individuals, and 123 patients with early HD. FINDINGS: The first participant was enrolled in January, 2008, and all assessments were completed by August, 2008. Cross-sectional analyses identified significant changes in whole-brain volume, regional grey and white matter differences, impairment in a range of voluntary neurophysiological motor, and oculomotor tasks, and cognitive and neuropsychiatric dysfunction in premanifest HD gene carriers with normal motor scores through to early clinical stage 2 disease. INTERPRETATION: We show the feasibility of rapid data acquisition and the use of multi-site 3T MRI and neurophysiological motor measures in a large multicentre study. Our results provide evidence for quantifiable biological and clinical alterations in HTT expansion carriers compared with age-matched controls. Many parameters differ from age-matched controls in a graded fashion and show changes of increasing magnitude across our cohort, who range from about 16 years from predicted disease diagnosis to early HD. These findings might help to define novel quantifiable endpoints and methods for rapid and reliable data acquisition, which could aid the design of therapeutic trials.


Assuntos
Biomarcadores/análise , Encéfalo/fisiopatologia , Doença de Huntington/diagnóstico , Doença de Huntington/fisiopatologia , Adolescente , Adulto , Idoso , Atrofia/diagnóstico , Atrofia/patologia , Atrofia/fisiopatologia , Encéfalo/patologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Diagnóstico Precoce , Feminino , Triagem de Portadores Genéticos/métodos , Predisposição Genética para Doença/genética , Testes Genéticos , Humanos , Doença de Huntington/genética , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Exame Neurológico/métodos , Valor Preditivo dos Testes , Valores de Referência , Adulto Jovem
15.
Brain ; 131(Pt 1): 196-204, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18056161

RESUMO

Huntington's disease is caused by a known genetic mutation and so potentially can be diagnosed many years before the onset of symptoms. Neuropathological changes have been found in both striatum and frontal cortex in the pre-symptomatic stage. Disruption of cortico-striatal white matter fibre tracts is therefore likely to contribute to the first clinical signs of the disease. We analysed diffusion tensor MR image (DTI) data from 25 pre-symptomatic gene carriers (PSCs) and 20 matched controls using a multivariate support vector machine to identify patterns of changes in fractional anisotropy (FA). In addition, we performed probabilistic fibre tracking to detect changes in 'streamlines' connecting frontal cortex to striatum. We found a pattern of structural brain changes that includes putamen bilaterally as well as anterior parts of the corpus callosum. This pattern was sufficiently specific to enable us to correctly classify 82% of scans as coming from a PSC or control subject. Fibre tracking revealed a reduction of frontal cortico-fugal streamlines reaching the body of the caudate in PSCs compared to controls. In the left hemispheres of PSCs we found a negative correlation between years to estimated disease onset and streamlines from frontal cortex to body of caudate. A large proportion of the fibres to the caudate body originate from the frontal eye fields, which play an important role in the control of voluntary saccades. This type of saccade is specifically impaired in PSCs and is an early clinical sign of motor abnormalities. A correlation analysis in 14 PSCs revealed that subjects with greater impairment of voluntary-guided saccades had fewer fibre tracking streamlines connecting the frontal cortex and caudate body. Our findings suggest a specific patho-physiological basis for these symptoms by indicating selective vulnerability of the associated white matter tracts.


Assuntos
Encéfalo/patologia , Doença de Huntington/patologia , Doença de Huntington/fisiopatologia , Movimentos Sacádicos , Adulto , Anisotropia , Mapeamento Encefálico/métodos , Corpo Estriado/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Lobo Frontal/patologia , Heterozigoto , Humanos , Doença de Huntington/genética , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Vias Neurais/patologia
16.
Inflamm Bowel Dis ; 25(9): 1569-1576, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-30810748

RESUMO

BACKGROUND AND AIMS: Inflammation of the pouch after ileal pouch-anal anastomosis (IPAA) can significantly impact quality of life and be difficult to treat. We assessed the effectiveness and safety of vedolizumab in Crohn's disease (CD) of the pouch and chronic antibiotic-dependent or antibiotic-refractory pouchitis. METHODS: This was a retrospective, multicenter cohort study at 5 academic referral centers in the United States. Adult patients with endoscopic inflammation of the pouch who received vedolizumab were included. The primary outcome was clinical response at any time point. Secondary outcomes included clinical remission, endoscopic response, and remission. Univariate analysis and multivariate analysis were performed for the effect of the following variables on clinical response: fistula, onset of pouchitis less than 1 year after IPAA, younger than 35 years old, gender, previous tumor necrosis factor inhibitor-alpha use, and BMI >30. RESULTS: Eighty-three patients were treated with vedolizumab for inflammation of the pouch between January 2014 and October 2017. Median follow-up was 1.3 years (interquartile range 0.7-2.1). The proportion of patients that achieved at least a clinical response was 71.1%, with 19.3% achieving clinical remission. Of the 74 patients with a follow-up pouchoscopy, the proportion of patients with endoscopic response and mucosal healing was 54.1% and 17.6%, respectively. Patients who developed pouchitis symptoms less than 1 year after undergoing IPAA were less likely to respond to vedolizumab, even after controlling for other risk factors. CONCLUSIONS: Vedolizumab is safe and effective in the management of CD of the pouch and chronic pouchitis. Further studies are needed to compare vedolizumab with other biologic therapies for pouchitis and CD of the pouch.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/cirurgia , Resistência a Medicamentos/efeitos dos fármacos , Pouchite/tratamento farmacológico , Proctocolectomia Restauradora/efeitos adversos , Adulto , Feminino , Seguimentos , Fármacos Gastrointestinais/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Pouchite/etiologia , Prognóstico , Estudos Retrospectivos , Estados Unidos
17.
Inflamm Bowel Dis ; 25(4): 767-774, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30295784

RESUMO

BACKGROUND: Crohn's disease (CD) of the pouch and chronic pouchitis occur in approximately 10% of patients after ileal pouch-anal anastomosis (IPAA) for refractory ulcerative colitis (UC) or UC-related dysplasia. The efficacy of anti-tumor necrosis factor (anti-TNF) agents and vedolizumab have been reported for the treatment of CD of the pouch and chronic pouchitis, but little is known regarding the use of ustekinumab in these settings. Our primary aim was to evaluate the efficacy of ustekinumab for these conditions. METHODS: This is a retrospective, multicenter cohort study evaluating the efficacy of ustekinumab in patients with CD of the pouch and chronic pouchitis. Clinical response or remission was judged by the treating physician's assessment at 6 months. RESULTS: Fifty-six patients (47 with CD of the pouch and 9 with chronic pouchitis) were included the study. Of these, 73% had previously been treated with either anti-TNF therapy, vedolizumab, or both after IPAA. Among patients with CD of the pouch and chronic pouchitis, 83% demonstrated clinical response 6 months after induction with ustekinumab. Responders demonstrated significantly less pouch inflammation on endoscopy when compared with nonresponders (29% vs 100%; P = 0.023). Higher mean body mass index at induction (26.3 vs 23.7; P = 0.033) and male sex (83% vs 30%; P = 0.014) were significant predictors of nonresponse to ustekinumab in those with CD of the pouch. CONCLUSION: In this refractory patient population, ustekinumab appears to be a safe and effective treatment for chronic pouchitis and CD of the pouch in biologic-naïve patients and those with prior anti-TNF or vedolizumab therapy failure. 10.1093/ibd/izx005_video1 izy302.video1 5844889626001.


Assuntos
Doença de Crohn/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Pouchite/complicações , Ustekinumab/uso terapêutico , Adulto , Doença de Crohn/etiologia , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Retrospectivos
18.
PLoS One ; 13(7): e0199389, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29975734

RESUMO

Sighted people predominantly use vision to navigate spaces, and sight loss has negative consequences for independent navigation and mobility. The recent proliferation of devices that can extract 3D spatial information from visual scenes opens up the possibility of using such mobility-relevant information to assist blind and visually impaired people by presenting this information through modalities other than vision. In this work, we present two new methods for encoding visual scenes using spatial audio: simulated echolocation and distance-dependent hum volume modulation. We implemented both methods in a virtual reality (VR) environment and tested them using a 3D motion-tracking device. This allowed participants to physically walk through virtual mobility scenarios, generating data on real locomotion behaviour. Blindfolded sighted participants completed two tasks: maze navigation and obstacle avoidance. Results were measured against a visual baseline in which participants performed the same two tasks without blindfolds. Task completion time, speed and number of collisions were used as indicators of successful navigation, with additional metrics exploring detailed dynamics of performance. In both tasks, participants were able to navigate using only audio information after minimal instruction. While participants were 65% slower using audio compared to the visual baseline, they reduced their audio navigation time by an average 21% over just 6 trials. Hum volume modulation proved over 20% faster than simulated echolocation in both mobility scenarios, and participants also showed the greatest improvement with this sonification method. Nevertheless, we do speculate that simulated echolocation remains worth exploring as it provides more spatial detail and could therefore be more useful in more complex environments. The fact that participants were intuitively able to successfully navigate space with two new visual-to-audio mappings for conveying spatial information motivates the further exploration of these and other mappings with the goal of assisting blind and visually impaired individuals with independent mobility.


Assuntos
Percepção Auditiva , Mapeamento Encefálico , Audição , Realidade Virtual , Visão Ocular , Percepção Visual , Adulto , Feminino , Humanos , Masculino , Aprendizagem em Labirinto , Software , Percepção Espacial , Interface Usuário-Computador , Adulto Jovem
19.
Medicine (Baltimore) ; 96(46): e8355, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29145246

RESUMO

RATIONALE: Microscopic colitis is a common cause of diarrhea. Pentoxifylline, a xanthine derivative with anti-tumor necrosis factor-alpha properties, is prescribed for intermittent claudication and other disorders. Our goal was to evaluate the outcomes of patients with microscopic colitis treated with pentoxifylline. PATIENT CONCERNS: Nine patients with microscopic colitis (8 collagenous colitis and 1 lymphocytic colitis) seen at Mayo Clinic, Rochester, between January 1, 1997 and November 30, 2016, were included. The median age was 56.9 years (range 51.6-60.2), 8 were female (89%), and the median disease duration was 64.8 months (range 60-109). The indications for treatment were budesonide refractoriness in 7 patients, budesonide dependence in 1 patient, and budesonide intolerance in 1 patient. DIAGNOSES: A histological diagnosis of microscopic colitis was confirmed in all patients. INTERVENTIONS: Pentoxifylline 400 mg three times a day was used for a median of 3 months (range 2.5-8.3). OUTCOMES: Complete response occurred in 1 patient (11%) and partial response in 3 patients (33%). The patient who achieved complete response was treated with pentoxifylline due to budesonide intolerance, and completed 43 months of successful maintenance therapy. There were no adverse effects reported. LESSONS: The majority of budesonide-experienced patients with active microscopic colitis did not respond to pentoxifylline. However, it was well-tolerated, with 1 patient achieving long-term remission and one-third of the cohort having a partial response. Larger controlled studies are required to evaluate the efficacy of pentoxifylline and predictors of response in microscopic colitis. In particular, patients who are not budesonide-refractory may be more likely to respond.


Assuntos
Colite Colagenosa/tratamento farmacológico , Colite Linfocítica/tratamento farmacológico , Pentoxifilina/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Phys Rev E Stat Nonlin Soft Matter Phys ; 74(3 Pt 1): 031912, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17025672

RESUMO

We model the spontaneous assembly of a capsid (a virus' closed outer shell) from many copies of identical units, using entirely irreversible steps and only information local to the growing edge. Our model is formulated in terms of (i) an elastic Hamiltonian with stretching and bending stiffness and a spontaneous curvature, and (ii) a set of rate constants for the addition of new units or bonds. An ensemble of highly irregular capsids is generated, unlike the well-known icosahedrally symmetric viruses, but (we argue) plausible as a way to model the irregular capsids of retroviruses such as HIV. We found that (i) the probability of successful capsid completion decays exponentially with capsid size; (ii) capsid size depends strongly on spontaneous curvature and weakly on the ratio of the bending and stretching elastic stiffnesses of the shell; (iii) the degree of localization of Gaussian curvature (a measure of facetedness) depends heavily on the ratio of elastic stiffnesses.


Assuntos
Capsídeo/química , HIV/química , Modelos Biológicos , Retroviridae/química
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