Inter-Cohort Validation of SuStaIn Model for Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disorder which spans several years from preclinical manifestations to dementia. In recent years, interest in the application of machine learning (ML) algorithms to personalized medicine has grown considerably, and a major challenge that such models face is the transferability from the research settings to clinical practice. The objective of this work was to demonstrate the transferability of the Subtype and Stage Inference (SuStaIn) model from well-characterized research data set, employed as training set, to independent less-structured and heterogeneous test sets representative of the clinical setting. The training set was composed of MRI data of 1043 subjects from the Alzheimer's disease Neuroimaging Initiative (ADNI), and the test set was composed of data from 767 subjects from OASIS, Pharma-Cog, and ViTA clinical datasets. Both sets included subjects covering the entire spectrum of AD, and for both sets volumes of relevant brain regions were derived from T1-3D MRI scans processed with Freesurfer v5.3 cross-sectional stream. In order to assess the predictive value of the model, subpopulations of subjects with stable mild cognitive impairment (MCI) and MCIs that progressed to AD dementia (pMCI) were identified in both sets. SuStaIn identified three disease subtypes, of which the most prevalent corresponded to the typical atrophy pattern of AD. The other SuStaIn subtypes exhibited similarities with the previously defined hippocampal sparing and limbic predominant atrophy patterns of AD. Subject subtyping proved to be consistent in time for all cohorts and the staging provided by the model was correlated with cognitive performance. Classification of subjects on the basis of a combination of SuStaIn subtype and stage, mini mental state examination and amyloid-β1-42 cerebrospinal fluid concentration was proven to predict conversion from MCI to AD dementia on par with other novel statistical algorithms, with ROC curves that were not statistically different for the training and test sets and with area under curve respectively equal to 0.77 and 0.76. This study proves the transferability of a SuStaIn model for AD from research data to less-structured clinical cohorts, and indicates transferability to the clinical setting

Visuo-spatial ability in colonoscopy simulator training

Visuo-spatial ability is associated with a quality of performance in a variety of surgical and medical skills. However, visuo-spatial ability is typically assessed using Visualization tests only, which led to an incomplete understanding of the involvement of visuo-spatial ability in these skills. To remedy this situation, the current study investigated the role of a broad range of visuo-spatial factors in colonoscopy simulator training. Fifteen medical trainees (no clinical experience in colonoscopy) participated in two psycho-metric test sessions to assess four visuo-spatial ability factors. Next, participants trained flexible endoscope manipulation, and navigation to the cecum on the GI Mentor II simulator, for four sessions within 1 week. Visualization, and to a lesser degree Spatial relations were the only visuo-spatial ability factors to correlate with colonoscopy simulator performance. Visualization additionally covaried with learning rate for time on task on both simulator tasks. High Visualization ability indicated faster exercise completion. Similar to other endoscopic procedures, performance in colonoscopy is positively associated with Visualization, a visuo-spatial ability factor characterized by the ability to mentally manipulate complex visuo-spatial stimuli. The complexity of the visuo-spatial mental transformations required to successfully perform colonoscopy is likely responsible for the challenging nature of this technique, and should inform training- and assessment design. Long term training studies, as well as studies investigating the nature of visuo-spatial complexity in this domain are needed to better understand the role of visuo-spatial ability in colonoscopy, and other endoscopic techniques

Introduction to Natural Fiber Reinforced Vinyl Ester and Vinyl Polymer Composites

In recent years, the polymer industry has intensified its efforts to produce renewable material based polymer. Therefore, the use of natural fiber composites has been widely considered in various engineering sectors to replace conventional synthetic composite usage. This is because natural fiber composite properties are easily disposed and environmentally friendly in generating economic and sustainability societies. Vinyl polymer is a group of matrices comprising of thermosets and thermoplastics that are normally preferred as matrices with natural fibers. Both groups have their own unique features in benefiting their applications. The composite made of thermoset resin cannot be reprocessed or recycled. The composites of the thermoset matrix tend to provide good mechanical strength, are fragile and have low tensile effects. This is in contrast to the properties of the thermoplastic polymer that can be formed and diluted without changing its physical properties. Thermoplastic has excellent impact resistance and ductile. However, various approaches continue to be carried out by researchers to meet the requirements of natural fiber composites in different applications

Plasma proteins predict conversion to dementia from prodromal disease.

PublishedJournal ArticleMulticenter StudyResearch Support, Non-U.S. Gov'tBACKGROUND: The study aimed to validate previously discovered plasma biomarkers associated with AD, using a design based on imaging measures as surrogate for disease severity and assess their prognostic value in predicting conversion to dementia. METHODS: Three multicenter cohorts of cognitively healthy elderly, mild cognitive impairment (MCI), and AD participants with standardized clinical assessments and structural neuroimaging measures were used. Twenty-six candidate proteins were quantified in 1148 subjects using multiplex (xMAP) assays. RESULTS: Sixteen proteins correlated with disease severity and cognitive decline. Strongest associations were in the MCI group with a panel of 10 proteins predicting progression to AD (accuracy 87%, sensitivity 85%, and specificity 88%). CONCLUSIONS: We have identified 10 plasma proteins strongly associated with disease severity and disease progression. Such markers may be useful for patient selection for clinical trials and assessment of patients with predisease subjective memory complaints.Medical Research Council (MRC)Alzheimer’s Research UKThe National Institute for Health Research (NIHR) Biomedical Research CentreBiomedical Research Unit for DementiaAddNeuroMed through the EU FP6 programInnovative Medicines Initiative Joint Undertaking under an EMIF grantEuropean Union’s Seventh Framework Programme (FP7/2007-2013

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Randomised double-blind trial of megestrol acetate vs placebo in treatment-naive advanced hepatocellular carcinoma

10.1038/bjc.2011.333British Journal of Cancer1057945-952BJCA

Short term effects of a low-carbohydrate diet in overweight and obese subjects with low HDL-C levels

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to evaluate short-term effects of a low-carbohydrate diet in overweight and obese subjects with low HDL-C levels.</p> <p>Methods</p> <p>Overweight (BMI between 25-30 kg/m²) or obese (BMI over 30 kg/m²) subjects with low HDL-C levels (men with HDL-C <1.03, women <1.29 mmol/l) were invited to the study. A 1400 kcal 75-gram carbohydrate (CHO) diet was given to women and an 1800 kcal 100-gram CHO diet was given to men for four weeks. The distribution of daily energy of the prescribed diet was 21-22% from CHO, 26-29% from protein and 49-53% from fat. Subjects completed a three-day dietary intake record before each visit. Anthropometric indices, body fat ratio, blood lipids, glucose and insulin were measured. Baseline and week-four results were compared with a Wilcoxon signed ranks test.</p> <p>Results</p> <p>Twenty-five women and 18 men participated. Basal median LDL-C level of men was 3.11 and basal median LDL-C level of women was 3.00 mmol/l. After four weeks of a low-carbohydrate diet, the median energy intake decreased from 1901 to 1307 kcal/day, daily energy from carbohydrate from 55% to 33%, body weight from 87.7 to 83.0 kg and HDL-C increased from 0.83 to 0.96 mmol/l in men (p < 0.002, for all). After four weeks of a low-carbohydrate diet, the median energy intake tended to decrease (from 1463 to 1243 kcal, p = 0.052), daily energy from carbohydrate decreased from 53% to 30% (p < 0.001) and body weight decreased from 73.2 to 70.8 kg (p < 0.001) in women, but HDL-C did not significantly change (from 1.03 to 1.01 mmol/l, p = 0.165). There were significant decreases in body mass index, waist circumference, body fat ratio, systolic blood pressure, total cholesterol, triglyceride and insulin levels in all subjects.</p> <p>Conclusions</p> <p>HDL-C levels increased significantly with energy restriction, carbohydrate restriction and weight loss in men. HDL-C levels didn't change in women in whom there was no significant energy restriction but a significant carbohydrate restriction and a relatively small but significant weight loss. Our results suggest that both energy and carbohydrate restriction should be considered in overweight and obese subjects with low HDL-C levels, especially when LDL-C levels are not elevated.</p