A novel artificial neural network method for biomedical prediction based on matrix pseudo-inversion

Biomedical prediction based on clinical and genome-wide data has become increasingly important in disease diagnosis and classification. To solve the prediction problem in an effective manner for the improvement of clinical care, we develop a novel Artificial Neural Network (ANN) method based on Matrix Pseudo-Inversion (MPI) for use in biomedical applications. The MPI-ANN is constructed as a three-layer (i.e., input, hidden, and output layers) feed-forward neural network, and the weights connecting the hidden and output layers are directly determined based on MPI without a lengthy learning iteration. The LASSO (Least Absolute Shrinkage and Selection Operator) method is also presented for comparative purposes. Single Nucleotide Polymorphism (SNP) simulated data and real breast cancer data are employed to validate the performance of the MPI-ANN method via 5-fold cross validation. Experimental results demonstrate the efficacy of the developed MPI-ANN for disease classification and prediction, in view of the significantly superior accuracy (i.e., the rate of correct predictions), as compared with LASSO. The results based on the real breast cancer data also show that the MPI-ANN has better performance than other machine learning methods (including support vector machine (SVM), logistic regression (LR), and an iterative ANN). In addition, experiments demonstrate that our MPI-ANN could be used for bio-marker selection as well.     

Industrial application of QbD and NIR chemometric models in quality improvement of immediate release tablets

Quality by Design (QbD) and chemometric models are different sides of the same coin. While QbD models utilize experimentally designed settings for optimization of some quality attributes, these settings can also be utilized for chemometric prediction of the same attributes. We aimed to synchronize optimization of comparative dissolution results of carvedilol immediate release tablets with chemometric prediction of dissolution profile and content uniformity of the product. As an industrial application, selection of variables for optimization was done by performing risk assessment utilizing the archived product records at the pharmaceutical site. Experimental tablets were produced with 20 different settings with the variables being contents of sucrose, sodium starch glycolate, lactose monohydrate, and avicel Ph 101. Contents of the excipients were modelled with F1 dissimilarity factor and F2 similarity factor in HCL, acetate, and USP dissolution media to determine the design space. We initiatively utilized Partial Least Square based Structural Equation Modelling (PLS-SEM) to explore how the excipients and their NIR records explained dissolution of the product. Finally, the optimized formula was utilized with varied content of carvedilol for chemometric prediction of the content uniformity.     

Curcumin produces neuroprotective effects via activating brain-derived neurotrophic factor/TrkB-dependent MAPK and PI-3K cascades in rodent cortical neurons

Curcumin is a major constituent of curcuma longa, a traditional medicine used to manage mental disorders effectively in China. The neuroprotective effects of curcumin have been demonstrated in our previous studies. In the present research, we confirmed this effect by showing that curcumin application promoted the viability of cultured rodent cortical neurons. Moreover, when neurons were pretreated with tyrosine kinase B (TrkB) antibody, known to inhibit the activity of brain-derived neurotrophic factor (BDNF), the protective effect of curcumin was blocked. Additionally, treatment of curcumin increased BDNF and phosphor-TrkB and both of these enhancements can be suppressed by ERK and PI-3K inhibitors. The administration of curcumin led to increased levels of phosphor-ERK and AKT, which were each blocked by MAPK and PI-3K inhibitors. Furthermore, the curcumin-induced increase in phosphorylated cyclic AMP response element binding protein (CREB), which has been implicated as a possible mediator of antidepressant actions, was prevented by MAPK and PI-3K inhibitors. Therefore, we hypothesize the neuroprotection of curcumin might be mediated via BDNF/TrkB-MAPK/PI-3K-CREB signaling pathway.     

Effects of statistical noise and digital filtering on the parameters calculated from the impulse response function

Radiotracers are widely used for the investigation of organ perfusion and function. One of the quantitative approaches to analyze radiotracer data is the calculation of the impulse response function, which is obtained by deconvolution analysis of the time-activity curves measured over the organ. Since exactness of the calculated impulse response function depends both on the counting statistics and on the deconvolution algorithm applied, computer simulated time-activity curves were used to test the least squares deconvolution program based on the matrix regularization algorithm. Criteria of clinical importance (error in the calculated organ function parameters) and criteria of mathematical importance (deconvolution and reconvolution error) were investigated. For three typical impulse response functions f(t), it was found that: 1. In cases of noncompartmental vascular-capillary f(t)'s, a high degree of smoothing is preferable during deconvolution, in this way the error becomes systematic but controllable. 2. Noncompartmental vascular-tubular f(t)'s are noise sensitive, but fortunately, noise in the data can be held to a minimum. 3. Compartmental f(t)'s need only a minimal degree of smoothing; their components can be identified in a second step using a multiexponential least squares fit.     

Evaluation of Ability of Biochemical Markers of Bone Turnover to Predict a Response to Increased Doses of HRT

Antiresorptive therapy is usually given in a fixed dose, and we hypothesized that some patients receiving standard doses of hormone replacement therapy (HRT) might benefit from a higher dose, particularly if their bone turnover decreases after increasing the dose of HRT. Eighty-eight women who had been receiving standard-dose (0.625 mg/day) conjugated equine estrogens (CEE) for at least one year were randomized to take either standard-dose (0.625 mg/day, n = 36) or high-dose (1.25 mg/day, n = 52) therapy. Subjects with a uterus were allowed to take either 10 mg of medroxyprogesterone cyclically or 5 mg daily, according to personal preference. Bone Mineral Density (BMD) and biochemical markers of bone turnover were followed for 2 years. Mean bone turnover decreased significantly (–4.1% to –19.1%) after 6 months of high-dose CEE. Decreases in serum BSAP (bone-specific alkaline phosphatase) and serum or urine NTX (N-terminal telopeptide crosslink of type I collagen) on high-dose therapy were not predictive of an improvement in BMD, but a decrease in serum CrossLaps did predict an improvement in BMD. Mean change in BMD in subjects with a significant decrease in serum CrossLaps at the anteroposterior spine was 3.1% ± 3.9% versus 1.2% ± 2.9% for subjects with no significant change in CrossLaps, P < 0.02. There was, however, a wide range of changes in BMD in patients with or without a significant change in CTX on high-dose HRT, making it impossible to predict an improvement in BMD based on an individuals changes in turnover. Measuring of bone density and bone turnover with better precision might be more successful in guiding individual dosing of antiresorptive therapy.This work is supported by a grant from the National Institutes of Health, grant #5 K08 AG000680-04; and from the William H. Milton Fund, Harvard Medical School, Boston, MA; and from Eli Lilly and Company, Indianapolis, IN; and from Mission Pharmacal, San Antonio, TX; and from the Upjohn Company, Kalamazoo, MI; and by NCRR grant RR 01032 supporting the General Clinical Research Center of Beth Israel Deaconess Medical Center.     

最小二乘一分光光度法测定复方氯丙嗪片的含量

复方氯丙嗪片中盐酸氯丙嗪及盐酸异丙嗪的化学结构及理化性质非常近似,紫外吸收光谱重叠相当严重,至今未见用分光光度法直接测定各自含量的报道。本文应用最小二乘-分光光度法测定了复方氯丙嗪片中盐酸氯丙嗪及盐酸异丙嗪的含量,方法简便,只需测定六个波长处的吸收值,即可同时得到该两组分的含量,其平均回收率:盐酸氯丙嗪为99.79％(n=17),变异系数2.6％,盐酸异丙嗪为99.98％(n=17),变异系数1.8％。     

Fast, Robust Identification of Nonlinear Physiological Systems Using an Implicit Basis Expansion

Because the number of parameters required by a Volterra series grows rapidly with both the length of its memory and the order of its nonlinearity, methods for identifying these models from measurements of input/output data are limited to low-order systems with relatively short memories. To deal with these computational and storage requirements one can either make extensive use of the structure of the Volterra series estimation problem to eliminate redundant storage and computations (e.g., the fast orthogonal algorithm), or apply a basis expansion, such as a Laguerre expansion, which seeks to reduce the number of model parameters, and hence, the size of the estimation problem. The use of an appropriate expansion basis can also decrease the noise sensitivity of the estimates. In this paper, we show how fast orthogonalization techniques can be combined with an expansion onto an arbitrary basis. We further demonstrate that the orthogonalization and expansion may be performed independently of each other. Thus, the results from a single application of the fast orthogonal algorithm can be used to generate multiple basis expansions. Simulations, using a simple nonlinear model of peripheral auditory processing, show the equivalence between the kernels estimated using a direct basis expansion, and those computed using the fast, implicit basis expansion technique which we propose. Running times for this new algorithm are compared to those for existing techniques. © 2000 Biomedical Engineering Society. PAC00: 8710+e, 8719Dd, 4364Bt, 0545-a     

Changing trends in otorhinolaryngological diseases at a non-government clinic in Jaipur

Background

Otorhinolaryngological (ENT) diseases are major health problem in India but the trends in occurrence of various disorders in clinical practice have not been well studied. To assess the types of such diseases and to determine changing trends in their incidence we performed this study.

Methods

The study was done at a non-government ENT center at Jaipur. From 1975 to 2005, >125000 patients of different diseases were evaluated here. The study includes randomly selected patients (n = 11454) from years 1980 to 2000 at an interval of 5 years to evaluate disease trends. Significance of trends was evaluated using least squares regression.

Results

In the years 1980, 1985, 1990, 1995 and 2000 mean age of patients was 26.60 ± 17.81 (range 0.16 to 85), 27.07 ± 16.91 (0.08 to 90), 28.30 ± 17.73 (0.25 to 90), 28.79 ± 17.8 (0.25 to 90) and 28.74 ± 17.81 (0.25 to 85) years respectively. 51 types of ENT diseases were observed of which 19 contributed to 76.8% (8807) patients and analysis was restricted to them. Chronic suppurative otitis media (2203, 19.2%), otitis externa (859, 7.5%), deviated nasal septum with nasal obstruction (717, 6.3%) and chronic tonsillitis (695, 6.1%) were the most common, followed by ear wax (569, 4.9%), sensorineural hearing loss (545, 4.7%), chronic rhinosinusitis (428, 3.7%) and epistaxis (320, 2.8%). There was increasing trend for stomatitis (b = 0.0014), deviated nasal septum (b = 0.0290), allergic rhinitis (b = 0.0023), epistaxis (b = 0.0002), acute tonsillitis (b = 0.0003), hoarseness (b = 0.0017), deaf mutism (b = 0.0005), sensorineural hearing loss (b = 0.0038), tinnitus (b = 0.0006) and ear wax (b = 0.0050). Declining trend was observed for chronic rhinosinusitis (b = −0.0155), otitis externa (b = −0.0063), chronic suppurative otitis media (b = −0.0001), acute otitis media ( = −0.0007), secretory otitis media (b = −0.0013), otosclerosis (b = −0.0007), vertigo (b = −0.0007), neck swelling (b = −0.0005) and chronic tonsillitis (b = −0.0194).

Conclusion

This study from an Indian urban ENT center shows a significantly increasing trend in chronic and degenerative ear diseases and decline in infection related diseases.     

数字小鼠切片数据集的自动配准

目的 实现小鼠动物标本的切片数据集的自动配准处理. 方法 以外部定标点圆心为基准点消除该数据集存在的水平晃动,并利用两定标点间距离结合最小二乘法计算相应的缩放比例曲线,解决切片图像中小鼠目标区域逐渐缩小的问题. 结果 经配准后的小鼠切片图像在连续播放时无明显的跳变和缩小,且三维重建获得的矢状面图像表面平滑,小鼠轮廓连续清晰,基本未变形. 结论 本研究完成了该套数据集的自动配准,经配准后的数据集适用于三维重建小鼠的整体结构,为后期开发数字化小鼠模型创造了条件.     

FDA的医疗器械监管科学:最小负担原则及应用

目的:研究美国FDA最小负担原则及应用,为我国医疗器械注册审评和科学监管提供参考.方法:通过文献研究,对2019年2月5日美国发布的《最小负担规范:概念和原则》(更新版)及其引用、关联的指导原则进行了分析.结果:最小负担原则是"用最少量的必要信息,在适当的时间、以最有效的方式,恰当地解决相关监管问题或事项",具体原则主...