Testing for a deficit in single-case studies: effects of departures from normality

In neuropsychological single-case research inferences concerning a patient's cognitive status are often based on referring the patient's test score to those obtained from a modestly sized control sample. Two methods of testing for a deficit (z and a method proposed by Crawford and Howell [Crawford, J. R. & Howell, D. C. (1998). Comparing an individual's test score against norms derived from small samples. The Clinical Neuropsychologist, 12, 482-486]) both assume the control distribution is normal but this assumption will often be violated in practice. Monte Carlo simulation was employed to study the effects of leptokurtosis and the combination of skew and leptokurtosis on the Type I error rates for these two methods. For Crawford and Howell's method, leptokurtosis produced only a modest inflation of the Type I error rate when the control sample N was small-to-modest in size and error rates were lower than the specified rates at larger N. In contrast, the combination of leptokurtosis and skew produced marked inflation of error rates for small Ns. With a specified error rate of 5%, actual error rates as high as 14.31% and 9.96% were observed for z and Crawford and Howell's method respectively. Potential solutions to the problem of non-normal data are evaluated.     

Comparison of three algorithms for multi-motor unit detection and waveform marking

Quantitative EMG (QEMG) techniques include automated motor unit action potential (MUAP) detection and marking of clinically useful waveform metrics. Different computer algorithms are available on modern EMG machines to perform these operations rapidly. However, the efficiency and accuracy of available algorithms are rarely directly compared. We have assessed three commercially available algorithms using both synthesized and biologic interference patterns and found differences among algorithms, some of which are clinically significant. Our results point out the importance of assessing for duplicate MUAPs (same waveform detected as two separate waveforms) and accuracy of markings used to determine MUAP metrics.     

Continued Driving and Time to Transition to Nondriver Status through Error-Specific Driving Restrictions

ABSTRACT

We developed driving restrictions that are linked to specific driving errors, allowing cognitively impaired individuals to continue to independently meet mobility needs while minimizing risk to themselves and others. The purpose of this project was to evaluate the efficacy and duration expectancy of these restrictions in promoting safe continued driving. We followed 47 drivers age 60 years and older for 18 months, evaluating driving performance at 6-month intervals. Results demonstrated restricted drivers had safety profiles similar to safe drivers and gained additional driving time to transition to nondrivers.     

数字X线摄影仿真教学系统在实验教学中的应用

目的构建基于数字X线摄影（digital radiography,DR）的虚拟仿真教学系统。方法运用Dreamware网页制作软件、Photoshop图像处理软件、Flash动画制作软件开发基于DR设备的虚拟仿真教学系统。结果为影像专业学生建立了一种虚拟仿真设备的实验教学环境。结论应用基于DR的仿真教学系统,巩固了学生的理论知识体系,激发了学生主动学习的兴趣,提高了学生熟练运用数字化影像设备进行临床实践的能力。     

如何利用模拟临床环境构建自主学习模式

随着社会的进步与科技的发展,医学模拟教育已普遍开展,国内外许多医学院校建立了临床技能培训中心,我们尝试将PBL、CBL、TBL等学习模式应用在临床技能实践教学中,并总结出在临床模拟环境中构建自主学习模式需注意的三个方面.     

扩展角对Diamond-Jet型超音速火焰喷涂流场的影响

采用计算流体力学方法对超音速火焰喷涂过程进行数值模拟,研究了扩展角的变化对燃烧场的影响。研究发现扩展角对马赫锥形成的位置具有影响,随着扩展角的变化,马赫锥产生的位置向燃烧室方向偏移,当扩展角为0°~3.0°时,最大马赫数随扩展角度增大而增大。研究了扩展角对Diamond Jet喷枪的温度场影响,当扩展角为0°~1.0°时,温度随扩展角的增加而降低,燃烧能转化为气体的动能;但是当扩展角度继续增加时,温度不再降低。     

Deposition of inhaled nanoparticles in the rat nasal passages: Dose to the olfactory region

In vivo experiments have shown that nanoparticles depositing in the rat olfactory region can translocate to the brain via the olfactory nerve. Quantitative predictions of the dose delivered by inhalation to the olfactory region are needed to clarify this route of exposure and to evaluate the dose-response effects of exposure to toxic nanoparticles. Previous in vivo and in vitro studies quantified the percentage of inhaled nanoparticles that deposit in the rat nasal passages, but olfactory dose was not determined. The dose to specific nasal epithelium types is expected to vary with inhalation rate and particle size. The purpose of this investigation, therefore, was to develop estimates of nanoparticle deposition in the nasal and, more specifically, olfactory regions of the rat. A three-dimensional, anatomically accurate, computational fluid dynamics (CFD) model of the rat nasal passages was employed to simulate inhaled airflow and to calculate nasal deposition efficiency. Particle sizes from 1 to 100?nm and airflow rates of 288, 432, and 576 ml/min (1, 1.5, and 2 times the estimated resting minute volume) were simulated. The simulations predicted that olfactory deposition is maximum at 6–9% of inhaled material for 3- to 4-nm particles. The spatial distribution of deposited particles was predicted to change significantly with particle size, with 3-nm particles depositing mostly in the anterior nose, while 30-nm particles were more uniformly distributed throughout the nasal passages.     

计算流体力学在喷雾干燥中的应用

计算流体力学是利用计算机求解流体流动的动量、能量和质量等方程,从而获得流体流动状态和各种热力学参数分布的一种数值模拟技术,该技术已成为研究流体流动和传质传热的重要工具.本文就计算流体力学在设计喷雾干燥仪结构、优化工艺参数、减少喷雾干燥过程塔壁沉积等方面的应用现状进行了综述.     

Numerical Simulation of Non-Uniformly Distributed Corrosion in Reinforced Concrete Cross-Section

Reinforced concrete structures can be strongly damaged by chloride corrosion of reinforcement. Rust accumulated around rebars involves a volumetric expansion, causing cracking of the surrounding concrete. To simulate the corrosion progress, the initiation phase of the corrosion process is first examined, taking into account the phenomena of oxygen and chloride transport as well as the corrosion current flow. This makes it possible to estimate the mass of produced rust, whereby a corrosion level is defined. A combination of three numerical methods is used to solve the coupled problem. The example object of the research is a beam cross-section with four reinforcement bars. The proposed methodology allows one to predict evolving chloride concentration and time to reinforcement depassivation, depending on the reinforcement position and on the location of a point on the bar surface. Moreover, the dependence of the corrosion initiation time on the chloride diffusion coefficient, chloride threshold, and reinforcement cover thickness is examined.     

Microsecond molecular dynamics simulation of Aβ42 and identification of a novel dual inhibitor of Aβ42 aggregation and BACE1 activity

Aim:

To study the conformational changes of Aβ₄₂ and discover novel inhibitors of both Aβ₄₂ aggregation and β-secretase (BACE1).

Methods:

A molecular dynamics (MD) simulation at a microsecond level was performed to explore stable conformations of Aβ₄₂ monomer in aqueous solution. Subsequently, structure-based virtual screening was used to search for inhibitors of both Aβ₄₂ aggregation and BACE1. Protein purification and in vitro activity assays were performed to validate the inhibition of the compounds identified via virtual screening.

Results:

The initial α-helical conformation of Aβ₄₂, which was unstable in aqueous solution, turned into a β-sheet mixed with a coil structure through a transient and fully random coil. The conformation of Aβ₄₂ mainly comprising β-sheets and coils structure was used for further virtual screening. Five compounds were identified as inhibitors for Aβ₄₂ aggregation, and one of them, AE-848, was discovered to be a dual inhibitor of both Aβ₄₂ aggregation and BACE1, with IC₅₀ values of 36.95 μmol/L and 22.70 μmol/L, respectively.

Conclusion:

A helical to β-sheet conformational change in Aβ₄₂ occurred in a 1.8 microsecond MD simulation. The resulting β-sheet structure of the peptide is an appropriate conformation for the virtual screening of inhibitors against Aβ₄₂ aggregation. Five compounds were identified as inhibitors of Aβ₄₂ aggregation by in vitro activity assays. It was particularly interesting to discover a dual inhibitor that targets both Aβ₄₂ aggregation and BACE1, the two crucial players in the pathogenesis of Alzheimer''s disease.