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1.
Front Plant Sci ; 10: 142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30858853

RESUMO

Understanding the spatial distribution of forage quality is important to address critical research questions in grassland science. Due to its efficiency and accuracy, there has been a widespread interest in mapping the canopy vegetation characteristics using remote sensing methods. In this study, foliar chlorophylls, carotenoids, and nutritional elements across multiple tallgrass prairie functional groups were quantified at the leaf level using hyperspectral analysis in the region of 470-800 nm, which was expected to be a precursor to further remote sensing of canopy vegetation quality. A method of spectral standardization was developed using a form of the normalized difference, which proved feasible to reduce the interference from background effects in the leaf reflectance measurements. Chlorophylls and carotenoids were retrieved through inverting the physical model PROSPECT 5. The foliar nutritional elements were modeled empirically. Partial least squares regression was used to build the linkages between the high-dimensional spectral predictor variables and the foliar biochemical contents. Results showed that the retrieval of leaf biochemistry through hyperspectral analysis can be accurate and robust across different tallgrass prairie functional groups. In addition, correlations were found between the leaf pigments and nutritional elements. Results provided insight into the use of pigment-related vegetation indices as the proxy of plant nutrition quality.

2.
Ann Neurol ; 85(5): 653-666, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30851128

RESUMO

OBJECTIVE: Rates of worsening and evolution to secondary progressive multiple sclerosis (MS) may be substantially lower in actively treated patients compared to natural history studies from the pretreatment era. Nonetheless, in our recently reported prospective cohort, more than half of patients with relapsing MS accumulated significant new disability by the 10th year of follow-up. Notably, "no evidence of disease activity" at 2 years did not predict long-term stability. Here, we determined to what extent clinical relapses and radiographic evidence of disease activity contribute to long-term disability accumulation. METHODS: Disability progression was defined as an increase in Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 (or greater) from baseline EDSS = 0, 1.0-5.0, and 5.5 or higher, respectively, assessed from baseline to year 5 (±1 year) and sustained to year 10 (±1 year). Longitudinal analysis of relative brain volume loss used a linear mixed model with sex, age, disease duration, and HLA-DRB1*15:01 as covariates. RESULTS: Relapses were associated with a transient increase in disability over 1-year intervals (p = 0.012) but not with confirmed disability progression (p = 0.551). Relative brain volume declined at a greater rate among individuals with disability progression compared to those who remained stable (p < 0.05). INTERPRETATION: Long-term worsening is common in relapsing MS patients, is largely independent of relapse activity, and is associated with accelerated brain atrophy. We propose the term silent progression to describe the insidious disability that accrues in many patients who satisfy traditional criteria for relapsing-remitting MS. Ann Neurol 2019;85:653-666.


Assuntos
Progressão da Doença , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/terapia , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
3.
Mult Scler ; 25(6): 837-847, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29761737

RESUMO

BACKGROUND: Long-term follow-up from the randomized trial of interferon beta-1b (IFNB-1b) permitted the assessment of different definitions of no evidence of disease activity (NEDA) for predicting long-term outcome in multiple sclerosis (MS). OBJECTIVE: To examine the predictive validity of different NEDA definitions. METHODS: Predictive validity for negative disability outcomes (NDOs) at 16 years and survival at 21 years post-randomization were assessed. NEDA in the first 2 years was defined as follows: clinical NEDA: no relapses or Expanded Disability Status Scale (EDSS) progression from baseline to Year 2; NEDA-3a: no relapses, no confirmed ⩾1-point EDSS progression, and no new T2-active lesions; NEDA-3b: no relapses, no EDSS progression, and no increase in T2 burden of disease (T2-BOD); and NEDA-4: no relapses, no EDSS progression, and no increase in T2-BOD or atrophy. NDOs were defined as death, need for wheelchair, EDSS ⩾6, or progressive MS. RESULTS: A total of 245 and 371 patients were evaluated at 16 and 21 years, respectively. Clinical NEDA predicted NDOs ( p = 0.0029), as did baseline EDSS ( p < 0.0001), baseline T2-BOD ( p < 0.0001), and change in T2-BOD ( p = 0.0033). IFNB-1b treatment ( p = 0.0251), relapse rate in the 2 years before study start ( p = 0.0260), T2-BOD at baseline ( p = 0.0014), and change in T2-BOD ( p = 0.0129) predicted survival at 21 years. CONCLUSION: Clinical NEDA predicted long-term disability outcome. By contrast, definitions of NEDA that included on-therapy changes in magnetic resonance imaging variables did not increase the predictive validity.


Assuntos
Adjuvantes Imunológicos/farmacologia , Progressão da Doença , Interferon beta-1b/farmacologia , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Índice de Gravidade de Doença , Adulto , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes
4.
Mult Scler ; 25(3): 408-418, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29310490

RESUMO

BACKGROUND: Electronic medical records (EMR) data are increasingly used in research, but no studies have yet evaluated similarity between EMR and research-quality data and between characteristics of an EMR multiple sclerosis (MS) population and known natural MS history. OBJECTIVES: To (1) identify MS patients in an EMR system and extract clinical data, (2) compare EMR-extracted data with gold-standard research data, and (3) compare EMR MS population characteristics to expected MS natural history. METHODS: Algorithms were implemented to identify MS patients from the University of California San Francisco EMR, de-identify the data and extract clinical variables. EMR-extracted data were compared to research cohort data in a subset of patients. RESULTS: We identified 4142 MS patients via search of the EMR and extracted their clinical data with good accuracy. EMR and research values showed good concordance for Expanded Disability Status Scale (EDSS), timed-25-foot walk, and subtype. We replicated several expected MS epidemiological features from MS natural history including higher EDSS for progressive versus relapsing-remitting patients and for male versus female patients and increased EDSS with age at examination and disease duration. CONCLUSION: Large real-world cohorts algorithmically extracted from the EMR can expand opportunities for MS clinical research.


Assuntos
Pesquisa Biomédica , Registros Eletrônicos de Saúde , Armazenamento e Recuperação da Informação , Esclerose Múltipla , Processamento de Linguagem Natural , Centros Médicos Acadêmicos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/fisiopatologia , Índice de Gravidade de Doença
5.
Sci Rep ; 8(1): 9018, 2018 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-29899544

RESUMO

Bats (Order: Chiroptera) harbor a high diversity of emerging pathogens presumably because their ability to fly and social behavior favor the maintenance, evolution, and dissemination of these pathogens. Until 2012, there was only one report of the presence of Hantavirus in bats. Historically, it was thought that these viruses were harbored primarily by rodent and insectivore small mammals. Recently, new species of hantaviruses have been identified in bats from Africa and Asia continents expanding the potential reservoirs and range of these viruses. To assess the potential of Neotropical bats as hosts for hantaviruses and its transmission dynamics in nature, we tested 53 bats for active hantaviral infection from specimens collected in Southeastern Brazil. Part of the hantaviral S segment was amplified from the frugivorous Carollia perspicillata and the common vampire bat Desmodus rotundus. DNA sequencing showed high similarity with the genome of Araraquara orthohantavirus (ARQV), which belongs to one of the more lethal hantavirus clades (Andes orthohantavirus). ARQV-like infection was detected in the blood, urine, and organs of D. rotundus. Therefore, we describe a systemic infection in Neotropical bats by a human pathogenic Hantavirus. We also propose here a schematic transmission dynamics of hantavirus in the study region. Our results give insights to new, under-appreciated questions that need to be addressed in future studies to clarify hantavirus transmission in nature and avoid hantavirus outbreaks.


Assuntos
Quirópteros/virologia , Reservatórios de Doenças/virologia , Infecções por Hantavirus/virologia , Hantavirus/fisiologia , Animais , Brasil , Quirópteros/sangue , Quirópteros/classificação , Variação Genética , Geografia , Hantavirus/classificação , Hantavirus/genética , Infecções por Hantavirus/sangue , Infecções por Hantavirus/transmissão , Interações Hospedeiro-Patógeno , Humanos , Filogenia , Análise de Sequência de DNA
6.
Mult Scler Relat Disord ; 21: 120-121, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29724376
7.
PLoS One ; 13(2): e0190043, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29438392

RESUMO

OBJECTIVE: To determine the relationship between highly-conserved extended-haplotypes (CEHs) in the major histocompatibility complex (MHC) and MS-susceptibility. BACKGROUND: Among the ~200 MS-susceptibility regions, which are known from genome-wide analyses of single nucleotide polymorphisms (SNPs), the MHC accounts for roughly a third of the currently explained variance and the strongest MS-associations are for certain Class II alleles (e.g., HLA-DRB1*15:01; HLA-DRB1*03:01; and HLA-DRB1*13:03), which frequently reside on CEHs within the MHC. DESIGN/METHODS: Autosomal SNPs (441,547) from 11,376 MS cases and 18,872 controls in the WTCCC dataset were phased. The most significant MS associated SNP haplotype was composed of 11 SNPs in the MHC Class II region surrounding the HLA-DRB1 gene. We also phased alleles at the HLA-A, HLA-C, HLA-B, HLA-DRB1, and HLA-DQB1 loci. This data was used to probe the relationship between CEHs and MS susceptibility. RESULTS: We phased a total of 59,884 extended haplotypes (HLA-A, HLA-C, HLA-B, HLA-DRB1, HLA-DQB1 and SNP haplotypes) from 29,942 individuals. Of these, 10,078 unique extended haplotypes were identified. The 10 most common CEHs accounted for 22% (13,302) of the total. By contrast, the 8,446 least common extended haplotypes also accounted for approximately 20% (12,298) of the total. This extreme frequency-disparity among extended haplotypes necessarily complicates interpretation of reported disease-associations with specific HLA alleles. In particular, the HLA motif HLA-DRB1*15:01~HLA-DQB1*06:02 is strongly associated with MS risk. Nevertheless, although this motif is almost always found on the a1 SNP haplotype, it can rarely be found on others (e.g., a27 and a36), and, in these cases, it seems to have no apparent disease-association (OR = 0.7; CI = 0.3-1.3 and OR = 0.7; CI = 0.2-2.2, respectively). Furthermore, single copy carriers of the a1 SNP-haplotype without this HLA motif still have an increased disease risk (OR = 2.2; CI = 1.2-3.8). In addition, even among the set of CEHs, which carry the Class II motif of HLA-DRB1*15:01~HLA-DQB1*06:02~a1, different CEHs have differing strengths in their MS-associations. CONCLUSIONS: The MHC in diverse human populations consists, primarily, of a very small collection of very highly-selected CEHs. Our findings suggest that the MS-association with the HLA-DRB1*15:01~HLA-DQB1*06:02 haplotype may be due primarily to the combined attributes of the CEHs on which this particular HLA-motif often resides.


Assuntos
Predisposição Genética para Doença , Haplótipos , Complexo Principal de Histocompatibilidade/genética , Esclerose Múltipla/genética , Humanos , Polimorfismo de Nucleotídeo Único
8.
Mult Scler Relat Disord ; 18: 109-116, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29141791

RESUMO

Establishing the relative efficacy and safety of the different disease modifying therapies (DMTs) in multiple sclerosis (MS) is critical to the choice of agent that clinicians recommend for individual MS patients. The best evidence for the relative efficacy of the different DMTs comes from head-to-head randomized clinical trials (RCTs). Understanding that outcome-measures with the best established validity are the relapse rate and the actual (not the "confirmed") change in the extended disability status scale (EDSS), we conclude from these head-to-head RCTs that interferon-beta (IFNß) given subcutaneously multiple times per week (either IFNß-1b or IFNß-1a) and glatiramer acetate (GA) are about equivalent in terms of efficacy and that both of these agents, as well as many of the other DMTs, are superior to weekly intramuscular IFNß-1a. Nevertheless, as ever-newer agents with novel mechanisms of action are brought to the marketplace, such direct head-to-head trials are becoming increasingly impractical, raising the need for alternative methods to draw reasonable inferences from less rigorous clinical data. One possible approach to judging comparative efficacy is to make comparisons across clinical trials using the complimentary analytic methods of calculating both the relative risk/rate and the absolute risk/rate reductions. A consideration and application of this analytic approach is undertaken here. It is only with an understanding of the safety and efficacy of the different agents that we can select, together with the patient, the right agent for the right person.


Assuntos
Fatores Imunológicos/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Pesquisa Comparativa da Efetividade , Humanos , Fatores Imunológicos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Vector Borne Zoonotic Dis ; 16(9): 569-76, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27454144

RESUMO

The variations in prevalence levels of two tick-borne rickettsial pathogens, Ehrlichia chaffeensis and Ehrlichia Ewingii, in a periurban environment were evaluated along with their ecological determinants. Tick life stage and sex, month of tick collection, landscape fragmentation, and ecological covariates specific to pasture and woodland sites were considered as explanatory covariates. Questing lone star ticks (Amblyomma americanum) were collected by flagging for an hour once every week during mid-April through mid-August in years 2013 and 2014. A total of 4357 adult and nymphal ticks (woodland = 2720 and pasture = 1637) were collected and assessed for pathogen prevalence by molecular methods. Female A. americanum ticks were more infected with E. chaffeensis than males or nymphs in woodland areas [♂ = 6.05%; ♀ = 12.0%; nymphs = 2.09%] and pastures [♂ = 8.05%; ♀ = 12.03%; nymphs = 3.33%], and the prevalence was influenced by edge density in the landscape. Higher E. ewingii infection was noted among female A. americanum ticks within woodland areas [♂ = 1.89%; ♀ = 2.14%; nymphs = 1.57%], but no such difference was evident in pastures [♂ = 1.03%; ♀ = 1.33%; nymphs = 1.12%]. Prevalence of E. ewingii was influenced by edge contrast index, and the percentage of pasture perimeter that was less than 20 meters from woodland areas. This study elucidates the complexity of tick-borne pathogen ecology and points to the need for further studies on the role of reservoir hosts, particularly that played by small vertebrates, which is not fully understood in the region.


Assuntos
Ecossistema , Ehrlichia/classificação , Ehrlichia/isolamento & purificação , Carrapatos/microbiologia , Animais , Cidades , DNA Bacteriano/genética , Ehrlichia/genética , Feminino , Kansas , Masculino , Ninfa/microbiologia , Reação em Cadeia da Polimerase , Zoonoses
10.
Ann Neurol ; 80(4): 499-510, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27464262

RESUMO

OBJECTIVE: To characterize the accrual of long-term disability in a cohort of actively treated multiple sclerosis (MS) patients and to assess whether clinical and magnetic resonance imaging (MRI) data used in clinical trials have long-term prognostic value. METHODS: This is a prospective study of 517 actively managed MS patients enrolled at a single center. RESULTS: More than 91% of patients were retained, with data ascertained up to 10 years after the baseline visit. At this last assessment, neurologic disability as measured by the Expanded Disability Status Scale (EDSS) was stable or improved compared to baseline in 41% of patients. Subjects with no evidence of disease activity (NEDA) by clinical and MRI criteria during the first 2 years had long-term outcomes that were no different from those of the cohort as a whole. 25-OH vitamin D serum levels were inversely associated with short-term MS disease activity; however, these levels had no association with long-term disability. At a median time of 16.8 years after disease onset, 10.7% (95% confidence interval [CI] = 7.2-14%) of patients reached an EDSS ≥ 6, and 18.1% (95% CI = 13.5-22.5%) evolved from relapsing MS to secondary progressive MS (SPMS). INTERPRETATION: Rates of worsening and evolution to SPMS were substantially lower when compared to earlier natural history studies. Notably, the NEDA 2-year endpoint was not a predictor of long-term stability. Finally, the data call into question the utility of annual MRI assessments as a treat-to-target approach for MS care. Ann Neurol 2016;80:499-510.


Assuntos
Progressão da Doença , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Esclerose Múltipla Crônica Progressiva/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Avaliação de Resultados em Cuidados de Saúde , Índice de Gravidade de Doença , Adulto , Pessoas com Deficiência , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Prognóstico
11.
J Wildl Dis ; 52(3): 766-9, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27314481

RESUMO

We screened blood samples from 560 wild rodents collected in southeastern Brazil for antibodies to a recombinant nucleoprotein (rN) of Junín virus. Six rodents were antibody positive (1.1%), demonstrating evidence of infection with mammarenaviruses in several species of Brazilian rodents.


Assuntos
Infecções por Arenaviridae/veterinária , Arenaviridae/classificação , Roedores/virologia , Animais , Animais Selvagens , Infecções por Arenaviridae/epidemiologia , Infecções por Arenaviridae/virologia , Brasil/epidemiologia , Estudos Soroepidemiológicos
12.
Plant Methods ; 12: 35, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27347001

RESUMO

BACKGROUND: Low cost unmanned aerial systems (UAS) have great potential for rapid proximal measurements of plants in agriculture. In the context of plant breeding and genetics, current approaches for phenotyping a large number of breeding lines under field conditions require substantial investments in time, cost, and labor. For field-based high-throughput phenotyping (HTP), UAS platforms can provide high-resolution measurements for small plot research, while enabling the rapid assessment of tens-of-thousands of field plots. The objective of this study was to complete a baseline assessment of the utility of UAS in assessment field trials as commonly implemented in wheat breeding programs. We developed a semi-automated image-processing pipeline to extract plot level data from UAS imagery. The image dataset was processed using a photogrammetric pipeline based on image orientation and radiometric calibration to produce orthomosaic images. We also examined the relationships between vegetation indices (VIs) extracted from high spatial resolution multispectral imagery collected with two different UAS systems (eBee Ag carrying MultiSpec 4C camera, and IRIS+ quadcopter carrying modified NIR Canon S100) and ground truth spectral data from hand-held spectroradiometer. RESULTS: We found good correlation between the VIs obtained from UAS platforms and ground-truth measurements and observed high broad-sense heritability for VIs. We determined radiometric calibration methods developed for satellite imagery significantly improved the precision of VIs from the UAS. We observed VIs extracted from calibrated images of Canon S100 had a significantly higher correlation to the spectroradiometer (r = 0.76) than VIs from the MultiSpec 4C camera (r = 0.64). Their correlation to spectroradiometer readings was as high as or higher than repeated measurements with the spectroradiometer per se. CONCLUSION: The approaches described here for UAS imaging and extraction of proximal sensing data enable collection of HTP measurements on the scale and with the precision needed for powerful selection tools in plant breeding. Low-cost UAS platforms have great potential for use as a selection tool in plant breeding programs. In the scope of tools development, the pipeline developed in this study can be effectively employed for other UAS and also other crops planted in breeding nurseries.

13.
J Neurol ; 263(7): 1418-26, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27177997

RESUMO

Early experience in MS generated concerns that interferon beta treatment might provoke onset or worsening of depression. The objective of the study was to compare depression incidence in relapsing-remitting MS patients receiving interferon beta-1b (IFNB-1b) or glatiramer acetate (GA) in the BEYOND trial. 891/897 (99 %) of English, French, Spanish and Italian speakers among 2244 patients randomized (2:2:1) to receive either IFNB-1b 500 µg, 250 µg, or GA 20 mg QD for 2-3.5 years submitted Beck Depression Inventory Second Edition (BDI-II) scores at screening and serially thereafter, in which scores ≥14 indicated depression. Baseline BDI-II scores ≥14 were reported in 232/891 patients (26.3 %), with no meaningful difference among the three treatment arms noted at this or at any other time during the study including trial end. Percentages of patients depressed by BDI-II scores deviated little in any arm at any time (IFNB-1b 500 µg: 24.7 %, IFNB-1b 250 µg: 24.4 %, GA: 32.4 %). Antidepressant usage was likewise similar among the three treatment arms (IFNB-1b 500 µg: 33.7 %, IFNB-1b 250 µg: 31.8 %, GA: 28.8 %) as was depression severity and the frequency with which non-blinded treating physicians recorded depression as an adverse event (IFNB-1b 500 µg: 17.2 %, IFNB-1b 250 µg: 17.0 %, GA: 14.4 %). Treating physicians attributed depression to IFNB-1b 250 µg therapy in 53.6 % and to GA in 21.9 % of instances. This large, prospective, randomized-controlled MS dataset showed no increased risk of depression above baseline values with standard or double-dose IFNB-1b or GA QD treatment.


Assuntos
Depressão/epidemiologia , Depressão/etiologia , Cooperação Internacional , Esclerose Múltipla/complicações , Esclerose Múltipla/epidemiologia , Adjuvantes Imunológicos/uso terapêutico , Adulto , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Acetato de Glatiramer/uso terapêutico , Humanos , Incidência , Interferon beta-1a/uso terapêutico , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/psicologia , Escalas de Graduação Psiquiátrica , Suicídio/psicologia , Adulto Jovem
14.
BMC Neurol ; 16: 56, 2016 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-27117889

RESUMO

BACKGROUND: Epidemiological observations regarding certain population-wide parameters (e.g., disease-prevalence, recurrence-risk in relatives, gender predilections, and the distribution of common genetic-variants) place important constraints on the possibilities for the genetic-basis underlying susceptibility to multiple sclerosis (MS). METHODS: Using very broad range-estimates for the different population-wide epidemiological parameters, a mathematical model can help elucidate the nature and the magnitude of these constraints. RESULTS: For MS no more than 8.5 % of the population can possibly be in the "genetically-susceptible" subset (defined as having a life-time MS-probability at least as high as the overall population average). Indeed, the expected MS-probability for this subset is more than 12 times that for every other person of the population who is not in this subset. Moreover, provided that those genetically susceptible persons (genotypes), who carry the well-established MS susceptibility allele (DRB1*1501), are equally or more likely to get MS than those susceptible persons, who don't carry this allele, then at least 84 % of MS-cases must come from this "genetically susceptible" subset. Finally, because men, compared to women, are at least as likely (and possibly more likely) to be susceptible, it can be demonstrated that women are more responsive to the environmental factors that are involved in MS-pathogenesis (whatever these are) and, thus, susceptible women are more likely actually to develop MS than susceptible men. Finally, in contrast to genetic susceptibility, more than 70 % of men (and likely also women) must have an environmental experience (including all of the necessary factors), which is sufficient to produce MS in a susceptible individual. CONCLUSIONS: As a result, because of these constraints, it is possible to distinguish two classes of persons, indicating either that MS can be caused by two fundamentally different pathophysiological mechanisms or that the large majority of the population is at no risk of the developing this disease regardless of their environmental experience. Moreover, although environmental-factors would play a critical role in both mechanisms (if both exist), there is no reason to expect that these factors are the same (or even similar) between the two.


Assuntos
Predisposição Genética para Doença , Modelos Teóricos , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/genética , Meio Ambiente , Feminino , Variação Genética , Genótipo , Humanos , Masculino , Prevalência , Risco
15.
PLoS Negl Trop Dis ; 10(4): e0004632, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27127994

RESUMO

Striped skunks are one of the most important terrestrial reservoirs of rabies virus in North America, and yet the prevalence of rabies among this host is only passively monitored and the disease among this host remains largely unmanaged. Oral vaccination campaigns have not efficiently targeted striped skunks, while periodic spillovers of striped skunk variant viruses to other animals, including some domestic animals, are routinely recorded. In this study we evaluated the spatial and spatio-temporal patterns of infection status among striped skunk cases submitted for rabies testing in the North Central Plains of US in a Bayesian hierarchical framework, and also evaluated potential eco-climatological drivers of such patterns. Two Bayesian hierarchical models were fitted to point-referenced striped skunk rabies cases [n = 656 (negative), and n = 310 (positive)] received at a leading rabies diagnostic facility between the years 2007-2013. The first model included only spatial and temporal terms and a second covariate model included additional covariates representing eco-climatic conditions within a 4 km(2) home-range area for striped skunks. The better performing covariate model indicated the presence of significant spatial and temporal trends in the dataset and identified higher amounts of land covered by low-intensity developed areas [Odds ratio (OR) = 3.41; 95% Bayesian Credible Intervals (CrI) = 2.08, 3.85], higher level of patch fragmentation (OR = 1.70; 95% CrI = 1.25, 2.89), and diurnal temperature range (OR = 0.54; 95% CrI = 0.27, 0.91) to be important drivers of striped skunk rabies incidence in the study area. Model validation statistics indicated satisfactory performance for both models; however, the covariate model fared better. The findings of this study are important in the context of rabies management among striped skunks in North America, and the relevance of physical and climatological factors as risk factors for skunk to human rabies transmission and the space-time patterns of striped skunk rabies are discussed.


Assuntos
Clima , Mephitidae , Vírus da Raiva/isolamento & purificação , Raiva/veterinária , Animais , Teorema de Bayes , América do Norte/epidemiologia , Raiva/epidemiologia , Análise Espaço-Temporal , Topografia Médica
16.
Mult Scler Relat Disord ; 6: 10-20, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27063617

RESUMO

Multiple sclerosis (MS) is a recurrent inflammatory disease of the central nervous system, which ultimately causes substantial disability in many patients. A key clinical feature of this disease is the occurrence of relapses, consisting of episodes of neurological dysfunction followed by periods of remission. This review considers in detail the importance of the occurrence of relapses to the ultimate course of MS and the impact of relap setreatment (both acutely and prophylactically) on the long-term outcome for individuals. The ultimate goal of therapy in MS is the reduction of long-term disability. Clinical trials in MS, however, typically only extend for a very short time period compared to the time it takes for disability to evolve. Consequently, short-term outcome measures that are associated with, and predict, future disability need to be identified. In this regard, not only are relapses a characteristic feature of MS, they have also been proven to be associated with the occurrence of long-term disability. Moreover, treatments that reduce the number and severity of these attacks improve the long-term prognosis.


Assuntos
Esclerose Múltipla/fisiopatologia , Avaliação da Deficiência , Humanos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/patologia
17.
PLoS One ; 11(3): e0150180, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26942604

RESUMO

This study aims to examine the spatio-temporal dynamics of Rocky Mountain spotted fever (RMSF) prevalence in four contiguous states of Midwestern United States, and to determine the impact of environmental and socio-economic factors associated with this disease. Bayesian hierarchical models were used to quantify space and time only trends and spatio-temporal interaction effect in the case reports submitted to the state health departments in the region. Various socio-economic, environmental and climatic covariates screened a priori in a bivariate procedure were added to a main-effects Bayesian model in progressive steps to evaluate important drivers of RMSF space-time patterns in the region. Our results show a steady increase in RMSF incidence over the study period to newer geographic areas, and the posterior probabilities of county-specific trends indicate clustering of high risk counties in the central and southern parts of the study region. At the spatial scale of a county, the prevalence levels of RMSF is influenced by poverty status, average relative humidity, and average land surface temperature (>35°C) in the region, and the relevance of these factors in the context of climate-change impacts on tick-borne diseases are discussed.


Assuntos
Clima , Febre Maculosa das Montanhas Rochosas/economia , Febre Maculosa das Montanhas Rochosas/epidemiologia , Análise Espaço-Temporal , Teorema de Bayes , Habitação , Humanos , Modelos Estatísticos , Dinâmica Populacional , Análise de Regressão , Fatores Socioeconômicos
18.
Vector Borne Zoonotic Dis ; 16(3): 205-11, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26824880

RESUMO

The potential distribution of Amblyomma americanum ticks in Kansas was modeled using maximum entropy (MaxEnt) approaches based on museum and field-collected species occurrence data. Various bioclimatic variables were used in the model as potentially influential factors affecting the A. americanum niche. Following reduction of dimensionality among predictor variables using principal components analysis, which revealed that the first two principal axes explain over 87% of the variance, the model indicated that suitable conditions for this medically important tick species cover a larger area in Kansas than currently believed. Soil moisture, temperature, and precipitation were highly correlated with the first two principal components and were influential factors in the A. americanum ecological niche. Assuming that the niche estimated in this study covers the occupied distribution, which needs to be further confirmed by systematic surveys, human exposure to this known disease vector may be considerably under-appreciated in the state.


Assuntos
Entropia , Ixodidae/fisiologia , Modelos Teóricos , Animais , Demografia , Meio Ambiente , Humanos , Kansas , Chuva , Solo , Temperatura
19.
Mult Scler ; 22(10): 1349-58, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26564998

RESUMO

BACKGROUND: Patient-Reported Expanded Disability Status Scale (PREDSS) tools are an attractive alternative to the Expanded Disability Status Scale (EDSS) during long term or geographically challenging studies, or in pressured clinical service environments. OBJECTIVES: Because the studies reporting these tools have used different metrics to compare the PREDSS and EDSS, we undertook an individual patient data level analysis of all available tools. METHODS: Spearman's rho and the Bland-Altman method were used to assess correlation and agreement respectively. RESULTS: A systematic search for validated PREDSS tools covering the full EDSS range identified eight such tools. Individual patient data were available for five PREDSS tools. Excellent correlation was observed between EDSS and PREDSS with all tools. A higher level of agreement was observed with increasing levels of disability. In all tools, the 95% limits of agreement were greater than the minimum EDSS difference considered to be clinically significant. However, the intra-class coefficient was greater than that reported for EDSS raters of mixed seniority. The visual functional system was identified as the most significant predictor of the PREDSS-EDSS difference. CONCLUSION: This analysis will (1) enable researchers and service providers to make an informed choice of PREDSS tool, depending on their individual requirements, and (2) facilitate improvement of current PREDSS tools.


Assuntos
Avaliação da Deficiência , Esclerose Múltipla/fisiopatologia , Medidas de Resultados Relatados pelo Paciente , Humanos
20.
JAMA Neurol ; 72(12): 1458-65, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26458124

RESUMO

IMPORTANCE: Low serum 25-hydroxyvitamin D (25[OH]D) levels are associated with an increased risk of multiple sclerosis (MS) as well as with increased disease activity and rate of progression in clinically isolated syndromes and early MS. OBJECTIVE: To assess the association between 25(OH)D and disease course and prognosis in patients with relapsing-remitting MS treated with interferon beta-1b. DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective cohort study assessing 25(OH)D levels and subsequent MS disease course and progression characterized by magnetic resonance imaging (MRI) and clinical end points. The study took place between November 2003 and June 2005; data analysis was performed between June 2013 and December 2014. The study was conducted among participants in the Betaferon Efficacy Yielding Outcomes of a New Dose (BEYOND) study, a large, phase 3, prospective, multicenter, blinded, randomized clinical trial. Patients were monitored for at least 2 years. Clinic visits were scheduled every 3 months, and MRI was performed at baseline and annually thereafter. Eligible patients included 1482 participants randomized to receive 250 µg or 500 µg of interferon-1b with at least 2 measurements of 25(OH)D obtained 6 months apart. EXPOSURES: Serum 25(OH)D measurements were performed at baseline, 6 months, and 12 months. MAIN OUTCOMES AND MEASURES: Main outcomes included cumulative number of new active lesions (T2 lesions and gadolinium acetate-enhancing lesions), change in normalized brain volume, relapse rate, and progression determined by the Expanded Disability Status Scale (EDSS). Statistical analyses were adjusted for age, sex, randomized treatment, region, disease duration, and baseline EDSS score. RESULTS: Overall, average 25(OH)D levels in 1482 patients were significantly inversely correlated with the cumulative number of new active lesions between baseline and the last MRI, with a 50.0-nmol/L increase in serum 25(OH)D levels associated with a 31% lower rate of new lesions (relative rate [RR], 0.69; 95% CI, 0.55-0.86; P = .001). The lowest rate of new lesions was observed among patients with 25(OH)D levels greater than 100.0 nmol/L (RR, 0.53; 95% CI, 0.37-0.78; P = .002). No significant associations were found between 25(OH)D levels and change in brain volume, relapse rates, or EDSS scores. Results were consistent following adjustment for HLA-DRB1*15 or vitamin D-binding protein status. CONCLUSIONS AND RELEVANCE: Among patients with MS treated with interferon beta-1b, higher 25(OH)D levels were associated with lower rates of MS activity observed on MRI. Results for brain atrophy and clinical progression were more equivocal.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Interferon beta-1b/uso terapêutico , Esclerose Múltipla/sangue , Esclerose Múltipla/tratamento farmacológico , Vitamina D/análogos & derivados , Adulto , Fatores Etários , Avaliação da Deficiência , Progressão da Doença , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Genótipo , Cadeias HLA-DRB1/genética , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/genética , Estudos Retrospectivos , Fatores de Tempo , Vitamina D/sangue , Proteína de Ligação a Vitamina D/genética
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