Abstract Objective Race/ethnic differences in carotid arterial function and structure exist among those with cerebrovascular disease, but whether differences persist among healthy populations is ...unknown. Our objective was to investigate differences in carotid artery diameter and stiffness between race/ethnic groups, and examine whether these race/ethnic differences were age-dependent. Methods Carotid diameters were assessed by B-mode ultrasound among 1536 participants from the Northern Manhattan Study (NOMAS), and carotid stiffness metrics were calculated. We used multivariable linear regression models to determine the relationship between race/ethnicity and both carotid arterial stiffness and carotid diastolic diameter. Results Mean participant age was 70 ± 9 years (Hispanics = 68 ± 8, blacks = 72 ± 9, and whites = 74 ± 9, p < 0.0001). Mean DDIAM was 6.2 ± 1.0 mm (Hispanics = 6.2 ± 0.9 mm, blacks = 6.3 ± 1.0 mm, and whites = 6.3 ± 1.0 mm, p < 0.005) and mean STIFF was 8.7 ± 6.3 (Hispanics = 8.5 ± 5.7, blacks = 9.2 ± 6.2 and whites = 8.9 ± 6.9, p < 0.02). In a model that adjusted for sociodemographics and vascular risk factors including hypertension, diabetes, dislipidemia, renal function, physical acticity and a history of known coronary artery diseases; age was positively associated with greater DDIAM in Hispanics ( p < 0.0001) but not among blacks or whites. Older age was associated with greater stiffness among Hispanics ( p < 0.0001) and blacks ( p < 0.003), but not among whites. Conclusions We found race/ethnic differences in the association between age and arterial stiffness and diameter, including age-dependent arterial dilation observed in Hispanics that was not observed among blacks or whites.
Purpose
The inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus (UF) are major fronto-capsular white matter pathways. IFOF connects frontal areas of the brain to parieto-occipital ...areas. UF connects ventral frontal areas to anterior temporal areas. Both fascicles are thought to subserve higher language and emotion roles. Controversy pertaining to their connectivity and subdivision persists in the literature, however.
Methods
High-definition fiber tractography (HDFT) is a non-tensor tractographic method using diffusion spectrum imaging data. Its major advantage over tensor-based tractography is its ability to trace crossing fiber pathways. We used HDFT to investigate subdivisions and cortical connectivity of IFOF and UF in 30 single subjects and in an atlas comprising averaged data from 842 individuals. A per-subject aligned, atlas-based approach was employed to seed fiber tracts and to study cortical terminations.
Results
For IFOF, we observed a tripartite arrangement corresponding to ventrolateral, ventromedial, and dorsomedial frontal origins. IFOF volume was not significantly lateralized to either hemisphere. UF fibers arose from ventromedial and ventrolateral frontal areas on the left and from ventromedial frontal areas on the right. UF volume was significantly lateralized to the left hemisphere. The data from the averaged atlas was largely in concordance with subject-specific findings. IFOF connected to parietal, occipital, but not temporal, areas. UF connected predominantly to temporal poles.
Conclusion
Both IFOF and UF possess subdivided arrangements according to their frontal origin. Our connectivity results indicate the multifunctional involvement of IFOF and UF in language tasks. We discuss our findings in context of the tractographic literature.
Sebaceous lesions, including sebaceous hyperplasia, sebaceomas, and sebaceous adenomas and carcinomas, are histologically distinctive adnexal proliferations with a spectrum of biological behavior ...ranging from benign to frankly malignant. The histologic distinction between sebaceous adenomas and carcinomas may be challenging, especially in cases showing atypical features and in small or partial biopsies. We studied multiple oncogenic and therapeutic related proteins by immunohistochemistry to identify differences in expression between benign and malignant sebaceous proliferations. A total of 27 cases, including 9 sebaceous adenomas, 4 sebaceomas, 8 sebaceous carcinomas, and 6 cases of sebaceous hyperplasia, were examined by immunohistochemistry, with antibodies directed against Ki-67 (MIB-1), bcl-2, p53, p21WAF1, p27Kip1, c-erbB-2 (Her-2/neu), CD117 (c-kit), cyclin D1, MDM2, CD99, MLH-1, and MSH-2. We found that sebaceous adenomas and sebaceomas stained like sebaceous hyperplasia did, whereas carcinomas had statistically significantly increased levels of p53 (50% versus 11%, respectively) and Ki-67 (30% versus 10%). The carcinomas also had significantly reduced levels of bcl-2 (7% versus 56%, respectively) and p21 (16% versus 34%) compared to the adenomas. Thus, a combination of several of these markers may be diagnostically useful in challenging cases. In addition, we found little or no Her-2/neu and CD117 staining, indicating that immunotherapy with Herceptin or Gleevac would likely not be useful for sebaceous carcinomas. Moreover, these results show that sebaceous adenomas and carcinomas are distinct neoplasms and provide no support for the theory that all sebaceous adenomas are truly malignant.
Objective
Childhood arthritis encompasses a heterogeneous family of diseases. Significant variation in clinical presentation remains despite consensus‐driven diagnostic classifications. Developments ...in data analysis provide powerful tools for interrogating large heterogeneous data sets. We report a novel approach to integrating biologic and clinical data toward a new classification for childhood arthritis, using computational biology for data‐driven pattern recognition.
Methods
Probabilistic principal components analysis was used to transform a large set of data into 4 interpretable indicators or composite variables on which patients were grouped by cluster analysis. Sensitivity analysis was conducted to determine key variables in determining indicators and cluster assignment. Results were validated against an independent validation cohort.
Results
Meaningful biologic and clinical characteristics, including levels of proinflammatory cytokines and measures of disease activity, defined axes/indicators that identified homogeneous patient subgroups by cluster analysis. The new patient classifications resolved major differences between patient subpopulations better than International League of Associations for Rheumatology subtypes. Fourteen variables were identified by sensitivity analysis to crucially determine indicators and clusters. This new schema was conserved in an independent validation cohort.
Conclusion
Data‐driven unsupervised machine learning is a powerful approach for interrogating clinical and biologic data toward disease classification, providing insight into the biology underlying clinical heterogeneity in childhood arthritis. Our analytical framework enabled the recovery of unique patterns from small cohorts and addresses a major challenge, patient numbers, in studying rare diseases.
Small companies find it difficult to implement production management systems. This causes problems of overproduction, high inventory and high rates of defective products. Lean Manufacturing acts as a ...methodology to achieve waste elimination. It is important that companies identify their current level of Lean to improve their operations. This work aims to present a model using fuzzy logic, applied in a small metallurgical industry. A Fuzzy inference model was specified and modeled on the software fuzzy toolbox MATLAB R2013aR. The simulation performed on the model took into account the current reality of the company, noting that there are no Lean metrics in its processes. A great advantage of the model is the possibility of adjustments for any type of organization since the input and output variables can receive other linguistic values. Keywords: Fuzzy logic. Lean manufacturing. Metallurgical industry. As pequenas empresas tem dificuldade em implementar sistemas de gestao da producao. Isso causa problemas de superproducao, alto estoque e altas taxas de produtos defeituosos. A Manufatura Enxuta (Lean Manufacturing) atua como uma metodologia para alcancar a eliminacao de desperdicios. E importante que as empresas identifiquem seu nivel atual de Lean para melhorar suas operacoes. Portanto,este trabalho tem como objetivo apresentar um modelo utilizando logica fuzzy, aplicado em uma pequena industria metalurgica. Um modelo de inferencia Fuzzy foi especificado e modelado no software fuzzy toolbox MATLAB R2013aR. A simulacao realizada no modelo levou em consideracao a realidade atual da empresa, pois foi observado que nao ha metricas Lean em seus processos. Uma grande vantagem do modelo e a possibilidade de ajustes para qualquer tipo de organizacao, uma vez que as variaveis de entrada e saida podem receber outros valores linguisticos. Palavras-chave: Logica fuzzy. Manufatura enxuta. Industria metalurgica.
Citrate is a key regulatory metabolic intermediate as it facilitates the integration of the glycolysis and lipid synthesis pathways. Inhibition of hepatic extracellular citrate uptake, by blocking ...the sodium-coupled citrate transporter (NaCT or SLC13A5), has been suggested as a potential therapeutic approach to treat metabolic disorders. NaCT transports citrate from the blood into the cell coupled to the transport of sodium ions. The studies herein report the identification and characterization of a novel small dicarboxylate molecule (compound 2) capable of selectively and potently inhibiting citrate transport through NaCT, both in vitro and in vivo. Binding and transport experiments indicate that 2 specifically binds NaCT in a competitive and stereosensitive manner, and is recognized as a substrate for transport by NaCT. The favorable pharmacokinetic properties of 2 permitted in vivo experiments to evaluate the effect of inhibiting hepatic citrate uptake on metabolic endpoints.
Aims
Tricuspid regurgitation (TR) is commonly observed in patients with severe left‐sided valvular heart disease (VHD). This study sought to assess TR frequency, management and outcome in this ...population.
Methods and results
Among 6883 patients with severe native left‐sided VHD or previous left‐sided valvular intervention enrolled in the EURObservational Research Programme prospective VHD II survey, moderate or severe TR was very frequent in patients with severe mitral VHD (30% when mitral stenosis, 36% when mitral regurgitation MR), especially in patients with secondary MR (46%), and rare in patients with severe aortic VHD (4% when aortic stenosis, 3% when aortic regurgitation). An increase in TR grade was associated with a more severe clinical presentation and a poorer 6‐month survival (p < 0.0001). Rates of concomitant tricuspid valve (TV) intervention at the time of left‐sided heart valve surgery were high at the time of mitral valve surgery (50% when mitral stenosis, 41% when MR). Concordance between class I indications (patients with severe TR) for concomitant TV surgery at the time of left‐sided valvular heart surgery according to guidelines and real‐practice decision‐making was very good (88% overall, 95% in patients operated on for MR).
Conclusion
In this large international prospective survey among patients with severe left‐sided VHD, moderate/severe TR was frequent in patients with mitral valve disease and was associated with a poorer outcome as TR grade increased. In patients with severe TR, compliance to guidelines for class I indications for concomitant TV surgery at the time of left‐sided heart valve surgery was very good.
Tricuspid regurgitation (TR): frequency, clinical presentation, management and outcome among patients with severe left‐sided valvular heart disease in Europe. ESC‐EORP, European Society of Cardiology‐EURObservational Research Programme; TV, tricuspid valve.
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