Longitudinal effects of metabolic syndrome on Alzheimer and vascular related brain pathology.

Background/aimsThis study examines the longitudinal effect of metabolic syndrome (MetS) on brain-aging indices among cognitively normal (CN) and amnestic mild cognitive impairment (aMCI) groups [single-domain aMCI (saMCI) and multiple-domain aMCI (maMCI)].MethodsThe study population included 739 participants (CN = 226, saMCI = 275, and maMCI = 238) from the Alzheimer's Disease Neuroimaging Initiative, a clinic-based, multi-center prospective cohort. Confirmatory factor analysis was employed to determine a MetS latent composite score using baseline data of vascular risk factors. We examined the changes of two Alzheimer's disease (AD) biomarkers, namely [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) regions of interest and medial temporal lobe volume over 5 years. A cerebrovascular aging index, cerebral white matter (cWM) volume, was examined as a comparison.ResultsThe vascular risk was similar in all groups. Applying generalized estimating equation modeling, all brain-aging indices declined significantly over time. Higher MetS scores were associated with a faster decline of cWM in the CN and maMCI groups but with a slower decrement of regional glucose metabolism in FDG-PET in the saMCI and maMCI groups.ConclusionAt the very early stage of cognitive decline, the vascular burden such as MetS may be in parallel with or independent of AD pathology in contributing to cognitive impairment in terms of accelerating the disclosure of AD pathology

Arts at the Core: Every School, Every Student

The profound impact of arts education on children and youth follows them throughout their lives. Arts education rewards our children by helping them to reach practical goals such as academic achievement and career success. Arts education enriches our youth with social, cultural and emotional benefits. As shown in study after study, a widely held belief in the positive value of arts education is shared by parents, teachers, school administrators and arts education experts.This belief is the reason that arts education has historically been an important part of the education of our children in the United States. However, deeper analysis both nationwide and here in Illinois reveals a gap between what individuals, educators and elected officials profess as the value of arts education and what is allocated to arts education in terms of budget, faculty, class time, curriculum, planning and evaluation.Illinois Creates is a broad-based statewide coalition of 150 education, business, civic and arts advocates dedicated to promoting a comprehensive, standards-based arts education program for all Illinois public school students

Biomarkers in ocular chronic graft versus host disease: tear cytokine- and chemokine-based predictive model.

Producción CientíficaPurpose: To develop a tear molecule level-based predictive model based on a panel of tear cytokines and their correlation with clinical features in ocular chronic graft versus host disease (cGVHD). Methods: Twenty-two ocular cGVHD patients and 21 healthy subjects were evaluated in a controlled environmental research laboratory (CERLab). Clinical parameters were recorded, and tears were collected. Levels of 15 molecules (epidermal growth factor [EGF], IL receptor antagonist [IL-1Ra], IL-1β, IL-2, IL-6, IL-8/CXCL8, IL-10, IL-12p70, IL-17A, interferon inducible protein [IP]-10/CXCL10, IFN-γ, VEGF, TNF-α, eotaxin 1, and regulated on activation normal T cell expressed and secreted [RANTES]) were measured by multiplex-bead assay and correlated with clinical parameters. Logistic regression was used to develop a predictive model. Leave-one-out cross-validation was applied. Classification capacity was evaluated in a cohort of individuals with dry eye (DE) of other etiologies different from GVHD. Results: Epidermal growth factor and IP-10/CXCL10 levels were significantly decreased in ocular cGVHD, positively correlating with tear production and stability and negatively correlating with symptoms, hyperemia, and vital staining. Interleukin-1Ra, IL-8/CXCL8, and IL-10 were significantly increased in ocular cGVHD, and the first two correlated positively with symptoms, hyperemia, and ocular surface integrity while negatively correlating with tear production and stability. Predictive models were generated, and the best panel was based on IL-8/CXCL8 and IP-10/CXCL10 tear levels along with age and sex, with an area under the receiving operating curve of 0.9004, sensitivity of 86.36%, and specificity of 95.24%. Conclusions: A predictive model based on tear levels of IL-8/CXCL8 and IP-10/CXCL10 resulted in optimal sensitivity and specificity. These results add further knowledge to the search for potential biomarkers in this devastating ocular inflammatory disease.Ministry of Economy and Competitiveness, Madrid, Spain, SAF-2010 15631 (AES)

Long-term radiographic and clinical-functional outcomes of isolated, displaced, closed talar neck and body fractures treated by ORIF: the timing of surgical management

Background: The main purpose of this retrospective case series study was to evaluate long-term radiographic and clinical outcomes of a consecutive series of patients diagnosed with isolated, displaced, closed talar neck or body fractures treated by open reduction and internal fixation (ORIF). Secondly, the aim was to verify the influence of the location of talar fractures on the outcomes, the prognostic value of the Hawkins sign, whether operative delays promote avascular necrosis (AVN) and if the fractures require emergent surgical management. Methods: From January 2007 to December 2012, at our institution, 31 patients underwent ORIF through the use of screws. On the basis of Inokuchi criteria, the injuries were divided between neck and body fractures, which were classified according to Hawkins and Sneppen, respectively. The patients included were divided into two groups in relation to fracture location and complexity. Radiographic assessment focused on reduction quality, bone healing, the Hawkins sign and post-traumatic arthritis (PTA) development. For the clinical evaluation, clinical-functional scores (AOFAS Ankle-Hindfoot Score; MFS; FFI-17; SF-36) and VAS were determined, and statistical analysis was performed. Results: 27 patients, 19 males and 8 females, mean age 38.3 years, were included with an average follow-up period of 83.2 months (range 49\u2013119). There were 9 neck and 19 body fractures; their reduction was anatomical or nearly anatomical in 22 cases, and all reached radiographic consolidation after a mean period of 3.4 months (range 1.7\u20137). The Hawkins sign was observed in 9 cases, in which necrosis did not develop. With a 0\u201311 day surgical timing interval, more than 60% of the patients obtained good or fair results with different scores, while 18 (66.7%) were completely satisfied (VAS: 9\u201310). The early complications included malunions (21.4%) and wound problems (25%); the late complications involved AVN (25%) and PTA (78.6%). Conclusions: Despite a high rate of long-term complications, satisfactory clinical results were achieved. Talar fracture location did not influence the outcomes, the Hawkins sign was confirmed as a positive prognostic factor, and operation timing did not influence AVN development. Hence, these injuries do not require emergent surgical management by ORIF

Optically Enhanced Bonding Workstation for Robust Bonding

Process control is one of the methods recommended by the FAA to reduce risk in fabrication of structurally bonded composite joints for aircraft structure based on guidance provided in circular AC-107B for certification of structurally bonded joints. An Optically Enhanced Bonding Workstation is presented here that reduces the risk in bonded joint fabrication. Results will be presented demonstrating the benefits of process monitoring and its ability to reduce risk in performing pre-bond composite surface preparation steps. This supports reduction in the timeline to certification of bonded composite structures through development of a robust bonding process upstream of any part certification steps. Sanding surface preparation has been identified as a high risk process step that is known to impact bond performance. Control of sanding during surface preparation can be performed using portable surface analysis tools previously identified including included gloss, color, Fourier Transform Infrared spectroscopy (FTIR) and optically stimulated electron emissions (OSEE). Threshold limits for the surface analysis tool measurements were determined based on an example objective bonding system utilizing a common EA9394 paste adhesive measured using standard double cantilever beam fracture toughness testing. The patented Optically Enhanced Bonding Workstation (OEBW), was tailored to monitor and control the epoxy composite surface preparation step. Surface analysis tool threshold limits were incorporated into the OEBW to demonstrate improved composite bond performance through process control. The surface analysis tools investigated here can easily be incorporated into an automated system due to their applicability to rapidly quantify the composite sanded surface treatment and their portability

An integrative analysis of cancer gene expression studies using Bayesian latent factor modeling

We present an applied study in cancer genomics for integrating data and inferences from laboratory experiments on cancer cell lines with observational data obtained from human breast cancer studies. The biological focus is on improving understanding of transcriptional responses of tumors to changes in the pH level of the cellular microenvironment. The statistical focus is on connecting experimentally defined biomarkers of such responses to clinical outcome in observational studies of breast cancer patients. Our analysis exemplifies a general strategy for accomplishing this kind of integration across contexts. The statistical methodologies employed here draw heavily on Bayesian sparse factor models for identifying, modularizing and correlating with clinical outcome these signatures of aggregate changes in gene expression. By projecting patterns of biological response linked to specific experimental interventions into observational studies where such responses may be evidenced via variation in gene expression across samples, we are able to define biomarkers of clinically relevant physiological states and outcomes that are rooted in the biology of the original experiment. Through this approach we identify microenvironment-related prognostic factors capable of predicting long term survival in two independent breast cancer datasets. These results suggest possible directions for future laboratory studies, as well as indicate the potential for therapeutic advances though targeted disruption of specific pathway components.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS261 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD.Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I-II/A-B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography-high resolution mass spectrometry metabolomics platform.Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10-7). Sex stratification indicated that the separation was driven by females (p=2.4×10-7) relative to males (p=4.0×10-4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10-3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p<0.0001), but not females (r=0.44; p=0.15), potentially related to observed dysregulation of the miR-29 family in the lung.These findings highlight the role of oxidative stress in COPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin-lysoPA axis, are associated with disease mechanisms and/or prevalence

Correlating Extreme Weather Conditions With Road Traffic Safety: A Unified Latent Space Model

The presence of extreme weather conditions is known to expose drivers to a higher risk to incur in road accidents. Quantifying the correlation between adverse weather conditions and road traffic safety is useful for several reasons such as planning preventive actions, managing vehicle fleets, and configuring alerting systems. However, since the risk of road accidents occurrences within a specific spatial region is influenced by several factors other than the weather conditions, quantifying the actual impact of adverse weather phenomena regardless of the effect of weather-unrelated conditions can be challenging. To tackle the aforesaid issue, this paper proposes to adopt a unified latent space model based on time series embeddings. Firstly, it encodes a subset of historical series reporting weather-related accident occurrences in specific risky areas into the high-dimensional vector representation. It also encodes the weather element measurements acquired by meteorological stations spread over the analyzed area. Then, to estimate the risk level of each region within the same spatial context it seeks the temporal risk patterns that are most similar to those observed in risky areas. The experiments carried out in a real case study confirm the applicability of the proposed approach