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.     

Context guides illness-identity: a qualitative analysis of Dutch university students' non-help-seeking behavior

The purpose of this article is to develop a context-based and identity-centered perspective on help-seeking. Recent approaches have indicated the inability of conventional models of help-seeking to account for the non-utilization of health care services in situations for which services, resources and information are adequately provided. We address this non-utilization from a perspective that explores the interactions between notions of health, illness, and identity formation, especially in highly transitional situations in which people are confused about their identity and sense of belonging. More specifically, we explore the non-utilization of health care services by Dutch university students. The results of 36 in-depth interviews show that the help-seeking behaviors of university students are closely associated with questions about identity, forms of agency, and styles of self-presentation, and are deeply influenced by the uncertain social and cultural context in which students are inserted. For example, being a 'normal' student was often regarded as more important than solving health problems, and stress was repeatedly portrayed as a constant and inevitable condition of everyday student life, giving a common language to express the burdens of the shared student experience. Some students even romanticized health problems. Eventually students with serious health problems avoided accessing health services.     

荧光原位杂交技术分析人结肠菌群方法研究

建立荧光原位杂交技术分析人体内结肠菌群的方法。取受试者新鲜粪便 ,选用 5种特异性的 16SrRNA寡核苷酸探针 ,检测粪便样本收集后的保存时间、温度 ,离心条件及样本固定液存放时间对杂交计数结果的影响。结果建立最佳实验条件为 :粪便样本收集后应尽快在 4℃下保存 ,放置时间不要超过 12小时即作处理 ;样本的适宜离心条件为 70 0g 2分钟 ;样本用多聚甲醛固定后在 - 80℃下存放时间不要超过 5个月。该方法具有较好的稳定性 ,可以有效地检出个体之间结肠菌群的差异。     

健康成人可接受牛奶摄入量实验研究

目的找出严重乳糖不耐受者最低可接受牛奶摄入量,观察此摄入量在健康成人中的耐受情况。方法采用氢呼气试验从38名受试者中筛选出8名有水样状腹泻的乳糖不耐受者,分成低、高剂量组参加饮奶试验。两组症状评分之和大致相等,据文献报道及单因素优选法(黄金分割法)确定两组对象分别饮用25g和38.2g奶粉(分别含6.25g和9.55g乳糖)和水冲调成的200ml牛奶,分析受试者氢呼气浓度变化值、症状评分、粪便乳糖含量(醋酸铅法)。采用随机整群抽样方法选取健康的100名青年、80名中年、100名老年人,观察摄入25g奶粉后出现的耐受症状。结果两组受试者在饮奶试验中无一例腹泻发生,仅有不同程度的轻微症状;高剂量组(B组)对象饮奶后,其氢呼气浓度、症状评分、粪便乳糖均高于低剂量组(A组)。健康成人饮用25g奶粉冲调的牛奶后,80.3%的对象未产生任何乳糖不耐受症状。结论结果表明健康成人即使为乳糖不耐受者也能饮用适量牛奶,大多数健康成人摄入25g奶粉(含乳糖6.25g)后不会出现任何乳糖不耐受症状,建议20g奶粉(含乳糖5g,配成160ml牛奶)作为我国成年人的最低可接受牛奶摄入量。     

Dyspnea severity, changes in dyspnea status and mortality in the general population: the Vlagtwedde/Vlaardingen study

Dyspnea is a predictor of mortality. The effects of dyspnea severity and changes in dyspnea status on all-cause and cause-specific mortality remain unclear. The Vlagtwedde/Vlaardingen study started in 1965 and subjects were re-examined every 3?years until 1989/1990. Vital status of all 8,465 subjects on December 31st, 2008 was assessed. Associations between mortality and dyspnea severity and changes in dyspnea status were investigated using Cox regression adjusted for gender, age, FEV₁ %predicted, place of residence, smoking and BMI. After 43?years of follow-up, 2,883 (39?%) of 7,360 subjects examined for dyspnea severity had died, 1,386 (19?%) due to cardiovascular disease, 267 (4?%) due to chronic obstructive pulmonary disease (COPD). Subjects with moderate and severe dyspnea had increased all-cause and cardiovascular mortality [moderate: HR?=?1.3 (95?% CI 1.2–1.5) and 1.4 (1.1–1.6), severe: 1.5 (1.1–2.0) and 1.9 (1.3–2.6) respectively] compared to asymptomatics. Severe dyspnea was significantly associated with COPD mortality [3.3 (2.0–5.2)]. Subjects who lost dyspnea had hazard ratios for all-cause and cause-specific mortality comparable to asymptomatics. Persistent dyspnea and dyspnea development were risk factors for all-cause, cardiovascular and COPD mortality [persistent: 2.0 (1.4–2.8), 1.9 (1.2–3.3) and 3.3 (1.2–8.9), development: 1.5 (1.2–1.8), 2.0 (1.5–2.6) and 3.8 (2.3–6.3) respectively]. Additionally, dyspnea effects on mortality were more pronounced in overweight/obese and older subjects and in subjects with better lung function. These results show that dyspnea is associated with mortality in a severity-dependent manner. Furthermore this study is the first showing that dyspnea remission normalizes mortality risk. Having or developing dyspnea is a risk factor for mortality.