Cross‐relaxation parameters in cortical bone assessed with different MR sequences

This study aimed to show evidence of MR cross‐relaxation effects in cortical bone and to compare different MR sequences for the quantification of cross‐relaxation parameters. Measurements were performed on bovine diaphysis samples with spectroscopic methods (inversion‐recovery, off‐resonance saturation) and with a variable flip angle (VFA) UTE imaging method on a 4.7 T laboratory‐assembled scanner. Cross‐relaxation parameter assessment was carried out via a two‐pool model simulation with a matrix algebra approach. A proton signal amplitude of 28 Mol/L was observed (equivalent water fraction of 25%). It was attributed to collagen‐bound water, with values of ~ 0.3 ms, a “long‐T₂” proton pool, in exchange with protons from the collagen macromolecules ( of 10–20 μs). Magnetization transfer (MT) effects were detected with all sequences. The best precision of model parameters was obtained with off‐resonance saturation; the fraction of collagen methylene protons was found in the range of 22–28% and the transverse relaxation time for collagen methylene protons was 11 μs (1% precision). The model parameters obtained were compatible with VFA‐UTE results but could not be assessed with acceptable accuracy and precision using this method. In vivo MT quantification using off‐resonance saturation with a single B₁ amplitude and offset frequency may provide information about the relative amount of collagen per unit volume in cortical bone.     

Model selection based on combined penalties for biomarker identification

The growing role of targeted medicine has led to an increased focus on the development of actionable biomarkers. Current penalized selection methods that are used to identify biomarker panels for classification in high-dimensional data, however, often result in highly complex panels that need careful pruning for practical use. In the framework of regularization methods, a penalty that is a weighted sum of the L₁ and L₀ norm has been proposed to account for the complexity of the resulting model. In practice, the limitation of this penalty is that the objective function is non-convex, non-smooth, the optimization is computationally intensive and the application to high-dimensional settings is challenging. In this paper, we propose a stepwise forward variable selection method which combines the L₀ with L₁ or L₂ norms. The penalized likelihood criterion that is used in the stepwise selection procedure results in more parsimonious models, keeping only the most relevant features. Simulation results and a real application show that our approach exhibits a comparable performance with common selection methods with respect to the prediction performance while minimizing the number of variables in the selected model resulting in a more parsimonious model as desired.     

慢性乙型肝炎患者外周血T淋巴细胞受体β链V区家族的表达及意义

目的探讨慢性乙型肝炎(CHB)患者外周血T淋巴细胞受体β链V区(TCR BV)各家族谱系的表达及其临床意义方法选择32例CHB患者(CHB组)及20例健康体检者(健康对照组),分别采集其外周血、肝素钠抗凝,分离单个核细胞,提取RNA并应用RT-PCR扩增TCR RV的24个家族,进行两组间扩增产物定量分析结果 CHB组△Ct5、△Ct7、△Ct15、△Ct22、△Ct23值与健康对照组比较,差异均有统计学意义(P<0.05)结论 CHB组TCR BV 24个家族BV5、BV7、BV15、BV22、BV23的扩增产物含量均较健康对照组下降,提示T淋巴细胞免疫应答可能参与CHB的发病过程     

Assessment of intracellular cytokines and regulatory cells in patients with autoimmune diseases and primary immunodeficiencies — Novel tool for diagnostics and patient follow-up

Serum and intracytoplasmic cytokines are mandatory in host defense against microbes, but also play a pivotal role in the pathogenesis of autoimmune diseases by initiating and perpetuating various cellular and humoral autoimmune processes.     

Pharmacoepidemiologic study of acute exacerbations of COPD: challenges and opportunities

Evaluation of: Rothberg MB, Pekow PS, Lahti M, Brody O, Skiest DJ, Lindenauer PK. Antibiotic therapy and treatment failure in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. JAMA 303(20), 2035–2042 (2010).

Guideline recommendations for the treatment of acute exacerbations of chronic obstructive pulmonary disease are derived from randomized clinical trials; they usually have a small sample size and are unrepresentative of patient populations. By contrast, observation data represent real-world patient population with large sample sizes and greater generalizability; however, appropriate methodologies are needed to analyze the data and make sound inference. This article reviews the study by Rothberg et al., summarizes the key findings, and extends the discussion to the challenges and opportunities of pharmacoepidemiologic studies in acute exacerbations of chronic obstructive pulmonary disease.     

Retirement and cognitive decline. A longitudinal analysis using SHARE data

We show that a new measure of cognitive decline, that can be computed in longitudinal surveys where respondents perform the same recall memory tests over the years, is highly predictive of the onset of dementia. Using SHARE data, we investigate the way retirement affects cognitive decline over time controlling for age, education and other confounding factors. We find that retirement has a long-term detrimental effect on cognition for individuals who retire at the statutory eligibility age. It plays instead a protective role for those who retire on an early retirement scheme.