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81.
Conceição Bettencourt Paula Coutinho Patrizia Rizzu João Vasconcelos Teresa Kay Teresa Cymbron Mafalda Raposo Peter Heutink Manuela Lima 《BMC neurology》2011,11(1):131
Background
Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disorder of late onset, which is caused by a CAG repeat expansion in the coding region of the ATXN3 gene. This disease presents clinical heterogeneity, which cannot be completely explained by the size of the repeat tract. MJD presents extrapyramidal motor signs, namely Parkinsonism, more frequently than the other subtypes of autosomal dominant cerebellar ataxias. Although Parkinsonism seems to segregate within MJD families, only a few MJD patients develop parkinsonian features and, therefore, the clinical and genetic aspects of these rare presentations remain poorly investigated. The main goal of this work was to describe two MJD patients displaying the parkinsonian triad (tremor, bradykinesia and rigidity), namely on what concerns genetic variation in Parkinson's disease (PD) associated loci (PARK2, LRRK2, PINK1, DJ-1, SNCA, MAPT, APOE, and mtDNA tRNA Gln T4336C). 相似文献82.
Understanding the factors driving innovation in energy technologies is of critical importance to mitigating climate change and addressing other energy-related global challenges. Low levels of innovation, measured in terms of energy patent filings, were noted in the 1980s and 90s as an issue of concern and were attributed to limited investment in public and private research and development (R&D). Here we build a comprehensive global database of energy patents covering the period 1970–2009, which is unique in its temporal and geographical scope. Analysis of the data reveals a recent, marked departure from historical trends. A sharp increase in rates of patenting has occurred over the last decade, particularly in renewable technologies, despite continued low levels of R&D funding. To solve the puzzle of fast innovation despite modest R&D increases, we develop a model that explains the nonlinear response observed in the empirical data of technological innovation to various types of investment. The model reveals a regular relationship between patents, R&D funding, and growing markets across technologies, and accurately predicts patenting rates at different stages of technological maturity and market development. We show quantitatively how growing markets have formed a vital complement to public R&D in driving innovative activity. These two forms of investment have each leveraged the effect of the other in driving patenting trends over long periods of time. 相似文献
83.
Karen E. Peterson Jennifer L. Spadano-Gasbarro Mary L. Greaney S. Bryn Austin Solomon Mezgebu Anne T. Hunt Emily A. Blood Chrissy Horan Henry A. Feldman Stavroula K. Osganian Maria F. Bettencourt Tracy K. Richmond 《PloS one》2015,10(8)
Introduction
Few dissemination evaluations exist to document the effectiveness of evidence-based childhood obesity interventions outside the research setting.Objective
Evaluate Healthy Choices (HC), a multi-component obesity prevention program, by examining school-level changes in weight-related behaviors and weight status and the association of implementation components with odds of overweight/obesity.Methods
We compared baseline and Year 3 school-level behavioral and weight status outcomes with paired t-tests adjusted for schools’ socio-demographic characteristics. We used generalized estimating equations to examine the odds of overweight/obesity associated with program components.Setting/Participants
Consecutive sample of 45 of 51 middle schools participating in the HC program with complete baseline and follow-up survey data including a subsample of 35 schools with measured anthropomentry for 5,665 7th grade students.Intervention
Schools developed a multi-disciplinary team and implemented an obesity prevention curriculum, before and after school activities, environmental and policy changes and health promotions targeting a 5-2-1 theme: eat ≥ 5 servings/day of fruits and vegetables (FV), watch ≤ 2 hours of television (TV) and participate in ≥ 1 hours/day of physical activity (PA) on most daysMain Outcome Measures
1) School-level percent of students achieving targeted behaviors and percent overweight/obese; and 2) individual odds of overweight/obesity.Results
The percent achieving behavioral goals over three years increased significantly for FV: 16.4 to 19.4 (p = 0.001), TV: 53.4 to 58.2 (p = 0.003) and PA: 37.1 to 39.9 (p = 0.02), adjusting for school size, baseline mean age and percent female, non-Hispanic White, and eligible for free and reduced price lunch. In 35 schools with anthropometry, the percent of overweight/obese 7th grade students decreased from 42.1 to 38.4 (p = 0.016). Having a team that met the HC definition was associated with lower odds of overweight/obesity (OR = 0.83, CI: 0.71–0.98).Conclusions and Relevance
The HC multi-component intervention demonstrated three-year improvements in weight-related behaviors and weight status across diverse middle schools. Team building appears important to the program’s effectiveness. 相似文献84.
Simon E Brill Anant RC Patel Richa Singh Alexander J Mackay Jeremy S Brown John R Hurst 《Respiratory research》2015,16(1)
Background
Exacerbations of non-cystic fibrosis bronchiectasis cause significant morbidity but there are few detailed data on their clinical course and associated physiological changes. The biology of an exacerbation has not been previously described.The purpose of this study was to describe changes in lung function, symptoms, health status and inflammation during the development and recovery from community-treated exacerbations.Methods
This was a prospective observational cohort study of 32 outpatients with non-cystic fibrosis bronchiectasis conducted between August 2010 and August 2012. Patients completed a symptom diary card and measured their peak expiratory flow rate (PEFR) daily. Exacerbations were defined as oral antibiotic treatment taken for a worsening of respiratory symptoms. Symptoms and peak flow at exacerbation were analysed, and further measurements including the COPD Assessment Test (CAT) and inflammatory markers were also compared to baseline values.Results
At baseline, health status was significantly related to lung function, prognostic severity and systemic inflammation. 51 exacerbations occurred in 22 patients. Exacerbation symptoms began a median (interquartile range) of 4 (2, 7) days before treatment started and the median exacerbation duration was 16 (10, 29) days. 16% had not recovered by 35 days. At exacerbation, mean PEFR dropped by 10.6% (95% confidence interval 6.9-14.2, p < 0.001) and mean CAT score increased by 6.3 units (3.6-9.1, p = 0.001), median symptom count by 4 (2.25, 6, p < 0.001), and mean CRP by 9.0mg/L (2.3-15.8, p = 0.011). Exacerbations where PEFR fell by ≥10% were longer with more symptoms at onset.Conclusion
Exacerbations of non-CF bronchiectasis are inflammatory events, with worsened symptoms, lung function and health status, and a prolonged recovery period. Symptom diary cards, PEFR and CAT scores are responsive to changes at exacerbation and may be useful tools for their detection and monitoring.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0167-9) contains supplementary material, which is available to authorized users. 相似文献85.
Barbosa JG Figueiredo B Bettencourt N Tavares JM 《Computer methods in biomechanics and biomedical engineering》2011,14(10):905-914
In this work, we present a technique to semi-automatically quantify the epicardial fat in non-contrasted computed tomography (CT) images. The epicardial fat is very close to the pericardial fat, being separated only by the pericardium that appears in the image as a very thin line, which is hard to detect. Therefore, an algorithm that uses the anatomy of the heart was developed to detect the pericardium line via control points of the line. From the points detected an interpolation was applied based on the cubic interpolation, which was also improved to avoid incorrect interpolation that occurs when the two variables are non-monotonic. The method is validated by using a set of 40 CT images of the heart of 40 human subjects. In 62.5% of the cases only minimal user intervention was required and the results compared favourably with the results obtained by the manual process. 相似文献
86.
Background
Interleukin-6 (IL-6) may have a protective role in acute liver disease but a detrimental effect in chronic liver disease. It is unknown whether IL-6 is associated with risk of liver-related mortality in humans.Aims
To determine if IL-6 is associated with an increased risk of all-cause, cardiovascular disease (CVD), cancer, and liver-related mortality.Methods
A prospective cohort study included 1843 participants who attended a research visit in 1984–87. Multiple covariates were ascertained including serum IL-6. Multivariable-adjusted Cox proportional hazards regression analyses were used to examine the association between serum IL-6 as a continuous (log transformed) variable with all-cause, CVD, cancer, and liver-related mortality. Patients with prevalent CVD, cancer and liver disease were excluded for cause-specific mortality.Results
The mean (± standard deviation) age and body-mass-index (BMI) of participants was 68 (±10.6) years and 25 (±3.7) Kg/m2, respectively. During the 25,802 person-years of follow-up, the cumulative all-cause, CVD, cancer, and liver-related mortality were 53.1% (N = 978), 25.5%, 11.3%, and 1.3%, respectively. The median (±IQR) length of follow-up was 15.3±10.6 years. In multivariable analyses, adjusted for age, sex, alcohol, BMI, diabetes, hypertension, total cholesterol, HDL, and smoking, one-SD increment in log-transformed serum IL-6 was associated with increased risk of all-cause, CVD, cancer, and liver-related mortality, with hazard ratios of 1.48 (95% CI, 1.33–1.64), 1.38 (95% CI, 1.16–1.65), 1.35 (95% CI, 1.02–1.79), and 1.88 (95% CI, 0.97–3.67), respectively. CRP adjustment attenuated the effects but the association between IL-6 and all-cause and CVD mortality remained statistically significant, independent of CRP levels.Conclusions
In community-dwelling older adults, serum IL-6 is associated with all-cause, CVD, cancer, and liver-related mortality. 相似文献87.
Urban scaling relations characterizing how diverse properties of cities vary on average with their population size have recently been shown to be a general quantitative property of many urban systems around the world. However, in previous studies the statistics of urban indicators were not analyzed in detail, raising important questions about the full characterization of urban properties and how scaling relations may emerge in these larger contexts. Here, we build a self-consistent statistical framework that characterizes the joint probability distributions of urban indicators and city population sizes across an urban system. To develop this framework empirically we use one of the most granular and stochastic urban indicators available, specifically measuring homicides in cities of Brazil, Colombia and Mexico, three nations with high and fast changing rates of violent crime. We use these data to derive the conditional probability of the number of homicides per year given the population size of a city. To do this we use Bayes' rule together with the estimated conditional probability of city size given their number of homicides and the distribution of total homicides. We then show that scaling laws emerge as expectation values of these conditional statistics. Knowledge of these distributions implies, in turn, a relationship between scaling and population size distribution exponents that can be used to predict Zipf's exponent from urban indicator statistics. Our results also suggest how a general statistical theory of urban indicators may be constructed from the stochastic dynamics of social interaction processes in cities. 相似文献
88.
Elisangela F Silva Mariana Orsi ?ngela L Andrade Rosana Z Domingues Breno M Silva Helena RC de Araújo Paulo FP Pimenta Michael S Diamond Eliseu SO Rocha Erna G Kroon Luiz CC Malaquias Luiz FL Coelho 《Journal of nanobiotechnology》2012,10(1):1-5
Background
Dengue is a major public health problem worldwide, especially in the tropical and subtropical regions of the world. Infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing secondary infection with a different serotype progresses to the severe form of the disease, dengue hemorrhagic fever/dengue shock syndrome. Currently, there are no licensed vaccines or antiviral drugs to prevent or treat dengue infections. Biodegradable nanoparticles coated with proteins represent a promising method for in vivo delivery of vaccines.Findings
Here, we used a murine model to evaluate the IgG production after administration of inactivated DENV corresponding to all four serotypes adsorbed to bovine serum albumin nanoparticles. This formulation induced a production of anti-DENV IgG antibodies (p < 0.001). However, plaque reduction neutralization assays with the four DENV serotypes revealed that these antibodies have no neutralizing activity in the dilutions tested.Conclusions
Our results show that while the nanoparticle system induces humoral responses against DENV, further investigation with different DENV antigens will be required to improve immunogenicity, epitope specicity, and functional activity to make this platform a viable option for DENV vaccines. 相似文献89.
Lucia V. Schottlaender Concei??o Bettencourt Aoife P. Kiely Annapurna Chalasani Viruna Neergheen Janice L. Holton Iain Hargreaves Henry Houlden 《PloS one》2016,11(2)
Background
The objective of this study was to evaluate whether the levels of coenzyme Q10 (CoQ10) in brain tissue of multiple system atrophy (MSA) patients differ from those in elderly controls and in patients with other neurodegenerative diseases.Methods
Flash frozen brain tissue of a series of 20 pathologically confirmed MSA patients [9 olivopontocerebellar atrophy (OPCA) type, 6 striatonigral degeneration (SND) type, and 5 mixed type] was used for this study. Elderly controls (n = 37) as well as idiopathic Parkinson''s disease (n = 7), dementia with Lewy bodies (n = 20), corticobasal degeneration (n = 15) and cerebellar ataxia (n = 18) patients were used as comparison groups. CoQ10 was measured in cerebellar and frontal cortex tissue by high performance liquid chromatography.Results
We detected a statistically significant decrease (by 3–5%) in the level of CoQ10 in the cerebellum of MSA cases (P = 0.001), specifically in OPCA (P = 0.001) and mixed cases (P = 0.005), when compared to controls as well as to other neurodegenerative diseases [dementia with Lewy bodies (P<0.001), idiopathic Parkinson''s disease (P<0.001), corticobasal degeneration (P<0.001), and cerebellar ataxia (P = 0.001)].Conclusion
Our results suggest that a perturbation in the CoQ10 biosynthetic pathway is associated with the pathogenesis of MSA but the mechanism behind this finding remains to be elucidated. 相似文献90.
Jill A. Rabinowitz Sally I.‐C. Kuo William Felder Rashelle J. Musci Amie Bettencourt Kelly Benke Danielle Y. Sisto Emily Smail George Uhl Brion S. Maher Anthony Kouzis Nicholas S. Ialongo 《Genes, Brain & Behavior》2019,18(5)
Polygenic propensity for educational attainment has been associated with higher education attendance, academic achievement and criminal offending in predominantly European samples; however, less is known about whether this polygenic propensity is associated with these outcomes among African Americans. Using an educational attainment polygenic score (EA PGS), the present study examined whether this score was associated with post‐secondary education, academic achievement and criminal offending in an urban, African American sample. Three cohorts of participants (N = 1050; 43.9% male) were initially recruited for an elementary school‐based universal prevention trial in a Mid‐Atlantic city and followed into young adulthood. Standardized tests of reading and math achievement were administered in first grade. At age 20, participants reported on their level of education attained, and records of incarceration were obtained from Maryland's Criminal Justice Information System. In young adulthood, DNA was collected and extracted from blood or buccal swabs and genotyped. An EA PGS was created using results from a large‐scale genome‐wide association study on educational attainment. A higher EA PGS was associated with a greater log odds of post‐secondary education. The EA PGS was not associated with reading achievement, although a significant relationship was found with math achievement in the third cohort. These findings contribute to the dearth of molecular genetics work conducted in African American samples and highlight that polygenic propensity for educational attainment is associated with higher education attendance. 相似文献