Analysis of Heart Rate Variability Based on the Graph Method

A method of analysis of heart rate variability based on the graph theory principle was suggested. The main parameters of the heart rate graph structure were determined and analyzed using models of harmonic oscillations, white noise, and various functional tests (including controllable respiration and mental load). The efficiency of the use of parameters of the heart rate graph for diagnosing some functional states was considered. A correlation of the parameters of the heart rate graph structure with the frequency characteristics of heart rate variability was studied. A general model of changes in the heart rate graph structure parameters at different levels of mental activity was constructed in terms of entropy changes.     

Inhalation/Exhalation Ratio Modulates the Effect of Slow Breathing on Heart Rate Variability and Relaxation

Slow breathing is widely applied to improve symptoms of hyperarousal, but it is unknown whether its beneficial effects relate to the reduction in respiration rate per se, or, to a lower inhalation/exhalation (i/e) ratio. The present study examined the effects of four ventilatory patterns on heart rate variability and self-reported dimensions of relaxation. Thirty participants were instructed to breathe at 6 or 12 breaths/min, and with an i/e ratio of 0.42 or 2.33. Participants reported increased relaxation, stress reduction, mindfulness and positive energy when breathing with the low compared to the high i/e ratio. A lower compared to a higher respiration rate was associated only with an increased score on positive energy. A low i/e ratio was also associated with more power in the high frequency component of heart rate variability, but only for the slow breathing pattern. Our results show that i/e ratio is an important modulator for the autonomic and subjective effects of instructed ventilatory patterns.     

Estimating Finite Rate of Population Increase for Sharks Based on Vital Parameters

The vital parameter data for 62 stocks, covering 38 species, collected from the literature, including parameters of age, growth, and reproduction, were log-transformed and analyzed using multivariate analyses. Three groups were identified and empirical equations were developed for each to describe the relationships between the predicted finite rates of population increase (λ’) and the vital parameters, maximum age (T_max), age at maturity (T_m), annual fecundity (f/R_c)), size at birth (L_b), size at maturity (L_m), and asymptotic length (L_∞). Group (1) included species with slow growth rates (0.034 yr^-1 < k < 0.103 yr^-1) and extended longevity (26 yr < T_max < 81 yr), e.g., shortfin mako Isurus oxyrinchus, dusky shark Carcharhinus obscurus, etc.; Group (2) included species with fast growth rates (0.103 yr^-1 < k < 0.358 yr^-1) and short longevity (9 yr < T_max < 26 yr), e.g., starspotted smoothhound Mustelus manazo, gray smoothhound M. californicus, etc.; Group (3) included late maturing species (L_m/L_∞ ≧ 0.75) with moderate longevity (T_max < 29 yr), e.g., pelagic thresher Alopias pelagicus, sevengill shark Notorynchus cepedianus. The empirical equation for all data pooled was also developed. The λ’ values estimated by these empirical equations showed good agreement with those calculated using conventional demographic analysis. The predictability was further validated by an independent data set of three species. The empirical equations developed in this study not only reduce the uncertainties in estimation but also account for the difference in life history among groups. This method therefore provides an efficient and effective approach to the implementation of precautionary shark management measures.     

A Novel Ex vivo Culture Method for the Embryonic Mouse Heart

Developmental studies in the mouse are hampered by the inaccessibility of the embryo during gestation. Thus, protocols to isolate and culture individual organs of interest are essential to provide a method of both visualizing changes in development and allowing novel treatment strategies. To promote the long-term culture of the embryonic heart at late stages of gestation, we developed a protocol in which the excised heart is cultured in a semi-solid, dilute Matrigel. This substrate provides enough support to maintain the three-dimensional structure but is flexible enough to allow continued contraction. In brief, hearts are excised from the embryo and placed in a mixture of cold Matrigel diluted 1:1 with growth medium. After the diluted Matrigel solidifies, growth medium is added to the culture dish. Hearts excised as late as embryonic day 16.5 were viable for four days post-dissection. Analysis of the coronary plexus shows that this method does not disrupt coronary vascular development. Thus, we present a novel method for long-term culture of embryonic hearts.     

A Proof-of-Principle Demonstration of a Novel Microarray-Based Method for Quantifying DNA Methylation Levels

Demethylation of CD11a (ITGAL; GeneID:3683; HGNC: 6148) and CD70 (TNFSF7; GeneID:970; HGNC:11937) regulatory regions in CD4⁺ T cells contributes to the development of autoreactivity and autoantibody overstimulation in systemic lupus erythematosus (SLE). In this study, we present a novel approach for measuring the methylation status of CD11a and CD70 promoter sequences. The procedure combines the standard method of bisulfite conversion of methylated CpG pairs with high-throughput oligonucleotide microarray-based technology that allows for rapid quantification of deoxycytosine and deoxymethylcytosine content in bisulfite-treated DNA samples. The microarrays were first used to generate a standard curve from fully methylated and fully unmethylated DNA samples using a one-dimensional linear regression equation that calculated fluorescence emission as a function of methylation levels. The methylation status of the CD70 and CD11a promoters in SLE and control CD4⁺ T cell samples were measured, and the microarray prediction was found to be highly accurate when compared to bisulfite sequencing. Furthermore, the microarrays were able to detect differences in the methylation status between SLE patient and healthy control samples. These results indicate that our new microarray-based assay could prove to be a highly reliable, rapid, and cost effective diagnostic and prognostic test for SLE.     

Collaborative Emission Reduction Model Based on Multi-Objective Optimization for Greenhouse Gases and Air Pollutants

CO₂ emission influences not only global climate change but also international economic and political situations. Thus, reducing the emission of CO₂, a major greenhouse gas, has become a major issue in China and around the world as regards preserving the environmental ecology. Energy consumption from coal, oil, and natural gas is primarily responsible for the production of greenhouse gases and air pollutants such as SO₂ and NO_X, which are the main air pollutants in China. In this study, a mathematical multi-objective optimization method was adopted to analyze the collaborative emission reduction of three kinds of gases on the basis of their common restraints in different ways of energy consumption to develop an economic, clean, and efficient scheme for energy distribution. The first part introduces the background research, the collaborative emission reduction for three kinds of gases, the multi-objective optimization, the main mathematical modeling, and the optimization method. The second part discusses the four mathematical tools utilized in this study, which include the Granger causality test to analyze the causality between air quality and pollutant emission, a function analysis to determine the quantitative relation between energy consumption and pollutant emission, a multi-objective optimization to set up the collaborative optimization model that considers energy consumption, and an optimality condition analysis for the multi-objective optimization model to design the optimal-pole algorithm and obtain an efficient collaborative reduction scheme. In the empirical analysis, the data of pollutant emission and final consumption of energies of Tianjin in 1996–2012 was employed to verify the effectiveness of the model and analyze the efficient solution and the corresponding dominant set. In the last part, several suggestions for collaborative reduction are recommended and the drawn conclusions are stated.     

A Real-Time Atrial Fibrillation Detection Algorithm Based on the Instantaneous State of Heart Rate

Atrial fibrillation (AF), the most frequent cause of cardioembolic stroke, is increasing in prevalence as the population ages, and presents with a broad spectrum of symptoms and severity. The early identification of AF is an essential part for preventing the possibility of blood clotting and stroke. In this work, a real-time algorithm is proposed for accurately screening AF episodes in electrocardiograms. This method adopts heart rate sequence, and it involves the application of symbolic dynamics and Shannon entropy. Using novel recursive algorithms, a low-computational complexity can be obtained. Four publicly-accessible sets of clinical data (Long-Term AF, MIT-BIH AF, MIT-BIH Arrhythmia, and MIT-BIH Normal Sinus Rhythm Databases) were used for assessment. The first database was selected as a training set; the receiver operating characteristic (ROC) curve was performed, and the best performance was achieved at the threshold of 0.639: the sensitivity (Se), specificity (Sp), positive predictive value (PPV) and overall accuracy (ACC) were 96.14%, 95.73%, 97.03% and 95.97%, respectively. The other three databases were used for independent testing. Using the obtained decision-making threshold (i.e., 0.639), for the second set, the obtained parameters were 97.37%, 98.44%, 97.89% and 97.99%, respectively; for the third database, these parameters were 97.83%, 87.41%, 47.67% and 88.51%, respectively; the Sp was 99.68% for the fourth set. The latest methods were also employed for comparison. Collectively, results presented in this study indicate that the combination of symbolic dynamics and Shannon entropy yields a potent AF detector, and suggest this method could be of practical use in both clinical and out-of-clinical settings.     

小剂量洋地黄对急性心肌梗死PCI术后合并心力衰竭患者心率变异性的影响

目的:探讨早期应用小剂量洋地黄类药物对急性心肌梗死(Acute myocardial infarction,AMI)行经皮冠状动脉介入治疗(Percutaneous coronary intervention,PCI)术后合并心力衰竭患者心率变异性(Heart rate variability,HRV)的影响。方法:入选32例在发病24小时内接受PCI治疗且合并心力衰竭的AMI患者,再灌注后随机分为洋地黄组(西地兰0.2 mg,n=17)和对照组(生理盐水20 m L,n=15)。在用药前、用药后30分钟、用药后3小时、用药后6小时、用药后12小时、用药后24小时进行5分钟HRV分析。结果:1洋地黄组的心率在用药6小时后显著小于对照组(P0.05);2洋地黄组SDNN在用药后3小时-6小时显著大于对照组(P0.05),两组RMSSD比较无显著统计学差别(P0.05);3洋地黄组LFnorm在用药后3小时-6小时显著大于对照组(P0.05);用药3小时后,洋地黄组HFnorm显著大于对照组(P0.05),LF/HF显著小于对照组(P0.05)。结论:小剂量洋地黄可以显著降低AMI PCI术后合并心力衰竭患者的心率、逆转迷走神经与交感神经活性的失衡状态,改善HRV。     

目标剂量螺内酯联合曲美他嗪对老年慢性心力衰竭患者炎症因子、RAAS及心率变异性的影响

摘要 目的：探讨目标剂量螺内酯（20 mg/d）联合曲美他嗪对老年慢性心力衰竭（CHF）患者炎症因子、肾素-血管紧张素-醛固酮系统（RAAS）、及心率变异性的影响。方法：选取120例老年CHF患者,随机分为对照组和研究组,各60例,其中对照组给予曲美他嗪治疗,研究组给予曲美他嗪联合目标剂量螺内酯治疗,对比两组疗效、炎症因子[超敏C反应蛋白（hs-CRP）、肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）]、RAAS指标 [肾素（PRA）、血管紧张素Ⅱ（AngⅡ）及醛固酮（ALD）]、心率变异性[24 h平均正常R-R间期标准差（SDNN）,24 h连续5 min节段平均正常R-R间期标准差（SDANN）,连续正常R-R间期差的均方根（rMSSD）]、心功能[左心室射血分数（LVEF）、左室收缩末期内径（LVESD）、左室舒张末期内径（LVEDD）]及安全性。结果：与对照组相比,研究组的总有效率更高（P<0.05）。治疗6个月后,两组hs-CRP、TNF-α、IL-6、LVESD、LVEDD、PRA、AngⅡ、ALD均较治疗前降低,且研究组上述指标低于对照组（P<0.05）。治疗6个月后,两组LVEF较治疗前升高,且研究组LVEF高于对照组（P<0.05）。治疗6个月后,研究组SDNN、SDANN、rMSSD均较治疗前升高,且研究组上述指标高于对照组（P<0.05）。两组不良反应发生率比较差异不明显（P>0.05）。结论：曲美他嗪联合目标剂量螺内酯治疗老年CHF患者疗效显著且安全性好,可明显改善患者的心功能、心率变异性,降低炎症因子水平,其可能是通过拮抗RAAS发挥作用。     

A Novel Improved Gram Staining Method Based on the Capillary Tube

In this work, an exploratory study was conducted to examine Gram staining based on the capillary tube. Each Gram staining step for all bacterial strains tested was completed in capillary tubes. The results showed that different Gram staining morphologies were clearly visible in the capillary tubes. The results presented here demonstrated that the improved method could effectively distinguish between Gram-positive and Gram-negative bacteria, and only small volumes of reagents were required in this method. Collectively, this efficient method could rapidly and accurately identify the types of bacteria. Therefore, our findings could be used as a useful reference study for other staining methods.Key words: Gram staining, capillary tube, bacteria, and glass slide

Since Hans Christian Joachim Gram reported a staining method in 1884 (Gram 1884), such a technique has experienced more than a century of development and has become frequently used in bacteriology. From 1940 to 1960, Gram staining’s clinical application reaches its peak (Kass 1987). In recent years, several automated instruments for Gram staining have also been applied for microbiological analysis (Baron et al. 2010; Li et al. 2020). With the development of modern science and technology, some new technologies are expected to replace Gram staining. For example, Sizemore et al. (1990) have developed an alternative Gram staining technique using a fluorescent lectin. Later on, several fluorescent Gram staining methods have been established, and some Gram staining techniques suitable for live bacterial suspension have been described (Mason et al. 1998; Fife et al. 2000; Forster et al. 2002; Kwon et al. 2019). Sharma et al. (2020) have found that acridine orange fluorescent staining is more sensitive than the Gram staining. Besides, Berezin et al. (2017) have established a method for detecting Gram-negative bacteria based on enhanced Raman spectroscopy. Lemozerskii et al. (2020) have also reported a method of bacterial discrimination using an acoustic resonator. However, Gram staining is still an vital detection method in practical application for many microbiologists and clinicians due to its rapidity and simplicity (Thompson et al. 2017; Jahangiri et al. 2018; Li et al. 2018a).Over the years, Gram staining has been modified for many times, such as the Brown-Hopps method, Brown-Brenn method, and Gram-Twort method (Brown and Brenn 1931; Brown and Hopps 1973; Peck and Badrick 2017), and these approaches as mentioned earlier are widely used in anatomical pathology laboratories. Through the comparison of various improved methods, it is found that Gram’s original four-step method is still used, and some researchers have adopted the three-step method, while its basic principle has not been changed. As reported by Huang and Cui (1996), the three-step Gram staining method combines the two steps of alcohol decolorization and re-staining procedure in one step. Although Gram staining is one of the most commonly used detection methods in clinical microbiology laboratories, many clinicians are skeptical of its results due to differences in operators, low control, and standardization (Samuel et al. 2016; Thomson 2016). Researchers have made efforts to improve the Gram staining’s accuracy and reliability over the past few years, such as repeated training and standardization of the staining procedure (Thomson 2016; Siguenza et al. 2019). In this study, we developed a standardized Gram staining procedure for bacterial identification using a capillary tube. A modified Gram staining method based on the capillary tube has not yet been reported to the best of our knowledge. Therefore, we proposed a novel improved Gram staining method to improve the accuracy of the detection results and Gram staining efficiency.Eight bacterial strains, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Bacillus Licheniformis, Serratia marcescens, Vibrio parahaemolyticus, Lactobacillus delbrueckii ssp. bulgaricus, and Streptococcus thermophilus were provided by the Laboratory of Microbial Engineering, College of Life Science, Luoyang Normal University. L. bulgaricus and S. thermophilus were inoculated into skim milk culture medium and maintained at 37°C for 12 h. S. marcescens, B. Licheniformis, E. coli, B. subtilis, V. parahaemolyticus, and S. aureus were inoculated into beef peptone agar slants and maintained at 37°C for 16 h.Capillary tubes with an internal diameter of 0.5 mm and a length of 100 mm were purchased from the Instrument Factory of West China University of Medical Sciences. Gram staining reagent was obtained from the Anhui Chaohuhongci Medical Equipment Co., Ltd.Procedure: (1) One or two drops of sterile water were placed in the center of a clean glass slide. An inoculating loop was hold in a flame until it was red-hot and then allowed to cool approximately 30 seconds. Subsequently, a loop of culture was transferred to the center of the slide. The sample was spread onto the slide using the inoculating loop, and a small volume of bacterial suspension was automatically transferred into the capillary tube.(2) The capillary tube was then heated by passing over a flame for several times until the liquid was completely evaporated. The capillary tube was naturally cooled in the air for several seconds.(3) One end of the capillary tube was hold upward, and the crystal violet solution was automatically transferred to the capillary tube, followed by standing for 1 minute. The remaining crystal violet solution of the capillary tube was then transferred to absorbent paper. The capillary tube was washed in a gentle and indirect stream of tap water for a few seconds, and samples were dried on absorbent paper.(4) One end of the capillary tube was hold upward, and Gram’s iodine solution was automatically transferred to the capillary tube, followed by standing for 1 minute. Subsequently, the capillary tube was washed using the same procedure as described above.(5) One end of the capillary tube was hold upward, and 95% ethanol was automatically transferred to the capillary tube, followed by standing for 30 seconds. Subsequently, the capillary tube was washed using the same procedure as described above.(6) One end of the capillary tube was hold upward, and the Safranin solution was automatically transferred to the capillary tube, followed by standing for 30 seconds to 1 minute. The subsequent procedure was the same as described above. Besides, conventional Gram staining was carried out according to the instructions from the reagent kit. According to the instructions, Gram-negative cells are in pink to red, and Gram-positive cells show a purple or blue color when observed under a microscope.The Gram staining is always the “first-stage criteria” in the preliminary identification of bacterial species according to their cell walls (Li et al. 2018b). Eight different bacterial species were examined to investigate our approach, and the strains were selected according to the Gram staining pattern. Gram-negative bacteria E. coli, V. parahaemolyticus, and S. marcescens were examined. Gram-positive bacteria S. thermophilus, L. bulgaricus, S. aureus, B. licheniformis and B. subtilis were also assessed. Fig. ​Fig.1,1, ​,2,2, and ​and33 illustrate the results of Gram staining of E. coli, V. parahaemolyticus, and S. marcescens, respectively. Fig. ​Fig.4,4, ​,5,5, ​,6,6, ​,7,7, and ​and88 show the Gram staining results of S. thermophilus, L. bulgaricus, S. aureus, B. subtilis, and B. licheniformis, respectively. These results were compared with those obtained using a glass slide for Gram staining. No matter spherical or rod-shaped or not, all bacterial strains could be differentiated into two classifications: Gram-positive and Gram-negative. Comparing these results, we found that the results obtained by the capillary tube method were consistent with the conventional Gram staining approach. It was worth mentioning that in contrast to direct heat fixation of bacteria on glass slides, heat fixation by passing the capillary tube over a flame should be carried out quickly and carefully. If the capillary tube was overheated, it might cause the capillary tube to rupture, and it is easy to blur the field of vision, making it challenging to observe the staining result (Fig. ​(Fig.9).9). Therefore, before the experiments, it is better to conduct a preliminary experiment and achieve the desired results.Open in a separate windowFig. 1.The Gram staining results of E. coli. A – Capillary sample, B – Glass slide sample.Open in a separate windowFig. 2.The Gram staining results of V. parahaemolyticus. A – Capillary sample, B – Glass slide sample.Open in a separate windowFig. 3.The Gram staining results of S. marcescens. A – Capillary sample, B – Glass slide sample.Open in a separate windowFig. 4.The Gram staining results of S. thermophiles. A – Capillary sample, B – Glass slide sample.Open in a separate windowFig. 5.The Gram staining results of L. bulgaricus. A – Capillary sample, B – Glass slide sample.Open in a separate windowFig. 6.The Gram staining results of S. aureus. A – Capillary sample, B – Glass slide sample.Open in a separate windowFig. 7.The Gram staining results of B. subtilis. A – Capillary sample, B – Glass slide sample.Open in a separate windowFig. 8.The Gram staining results of B. Licheniformis. A – Capillary sample, B – Glass slide sample.Open in a separate windowFig. 9.The microstructure of the overheated capillary tube.Several studies (Chimento et al. 1996; Wada et al. 2012; Li Zhu 2018b) have already pointed out that the property of the bacterial cell wall determines whether the organism will be Gram-positive or Gram-negative, and it plays a role in the choice of antibiotics when infection occurs. Since it has frequently been observed that not all bacteria react in the same manner to such staining procedure (Hale and Bisset 1956), it is necessary to make more tests upon a representative selection of Gram-positive and Gram-negative bacteria in future studies.Molecular biology techniques and high-precision measurement systems have been successfully developed, and they can distinguish bacterial types in clinical samples and improve microbial detection (Klaschik et al. 2002; Dolch et al. 2016; Kim et al. 2018). However, it is still urgently needed to develop a rapid and straightforward Gram staining approach to detect bacteria, especially for those who have only primary experimental conditions. Our results indicated a promising method for bacterial differentiation using the capillary tube as a carrier. Successful differentiation required only small volumes of reagents, and the results were achieved within a few minutes by applying an optical microscope. In addition, the method proposed in this paper had reference value to other staining methods requiring expensive reagents.In the present study, the improved Gram staining method was developed based on the pure cultures, and it was only a comparison of the staining results between known Gram-negative and Gram-positive bacteria in a glass slide and capillary tube. In order to improve the accuracy and stability of the results, future study is necessary to detect more bacterial species. In addition, the modified method was not applicable for direct Gram staining of clinical samples. In the future, it may have a positive effect by developing a special method for processing clinical samples.The experimental results demonstrated that an improved Gram staining method was suitable for differentiating the strains tested in our laboratory. The method could rapidly discriminate Gram-positive and Gram-negative bacteria. Besides, the method only required small volumes of reagents. A much more comfortable and reproducible Gram staining approach can be developed for microbiology research based on our studies.     

A Review of Methods for Non-Invasive Heart Rate Measurement on Wrist

When evaluating general health condition on a patient, heart rate is an essential indicator as it is directly representative of the cardiac system state. Continuous measurement methods of heart rate are required for ambulatory monitoring involved in preliminary diagnostic indicators of cardiac diseases or stroke. The growing number of recent developments in wearable devices is reflective of the increasing demand in wrist-worn activity trackers for fitness and health applications. Indeed, the wrist represents a convenient location in terms of form factor and acceptability for patients. While most commercially-available devices are based on optical methods for heart rate measurement, others methods were also developed, based on various physiological phenomena. This review is focused on heart rate measurement methods located on forearm and more specifically on the wrist. For each method, the physiological mechanism involved is described, and the associated transducers for bio-signal acquisition as well as practical developments and prototypes are presented. Methods are discussed on their advantages, limitations and their suitability for an ambulatory use. More specifically, the superposition of motion artefacts over the signal of interest is one of the largest drawbacks for these methods, when used out of laboratory conditions. As such, artefact reduction techniques proposed in the literature are also presented and discussed.     

基于快速沃尔什变换的分子子序列识别

提出了一种基于快速沃尔什变换的分子子序列识别的方法。这种方法不仅能快速识别出子序列并确定子序列的位置，而且极大地降低了CPU运行时间和计算复杂度，结合实例对这种方法进行了分析。     

A Novel Method in the Stratification of Post-Myocardial-Infarction Patients Based on Pathophysiology

Objectives

We proposed that the severity of ST-segment elevation myocardial infarction (STEMI) could be classified based on pathophysiological changes.

Methods

First-STEMI patients were classified within hospitalization. Grade 0: no detectable myocardial necrosis; Grade 1: myocardial necrosis without functional and morphological abnormalities; Grade 2: myocardial necrosis with reduced LVEF; Grade 3: reduced LVEF on the basis of cardiac remodeling; Grade 4: mitral regurgitation additional to the Grade-3 criteria.

Results

Of 180 patients, 1.7, 43.9, 26.1, 23.9 and 4.4% patients were classified as Grade 0 to 4, respectively. The classification is an independent predicator of 90-day MACEs (any death, resuscitated cardiac arrest, acute heart failure and stroke): the rate was 0, 5.1, 8.5, 48.8 and 75% from Grade 0 to 4 (p<0.001), respectively. The Grade-2 patients were more likely to have recovered left ventricular ejection fraction than the Grade-3/4 patients did after 90 days (48.9% vs. 19.1%, p<0.001). Avoiding complicated quantification, the classification served as a good reflection of infarction size as measured by cardiac magnetic resonance imaging (0±0, 15.68±8.48, 23.68±9.32, 36.12±11.35 and 40.66±14.33% of the left ventricular mass by Grade 0 to 4, P<0.001), and with a comparable prognostic value (AUC 0.819 vs. 0.813 for infarction size, p = 0.876 by C-statistics) for MACEs.

Conclusions

The new classification represents an easy and objective method to scale the cardiac detriments for STEMI patients.     

A Novel Dictionary Based Computer Vision Method for the Detection of Cell Nuclei

Cell nuclei detection in fluorescent microscopic images is an important and time consuming task in a wide range of biological applications. Blur, clutter, bleed through and partial occlusion of nuclei make individual nuclei detection a challenging task for automated image analysis. This paper proposes a novel and robust detection method based on the active contour framework. Improvement over conventional approaches is achieved by exploiting prior knowledge of the nucleus shape in order to better detect individual nuclei. This prior knowledge is defined using a dictionary based approach which can be formulated as the optimization of a convex energy function. The proposed method shows accurate detection results for dense clusters of nuclei, for example, an F-measure (a measure for detection accuracy) of 0.96 for the detection of cell nuclei in peripheral blood mononuclear cells, compared to an F-measure of 0.90 achieved by state-of-the-art nuclei detection methods.     

A Novel Method of Estimating Dose Responses for Polymer Gels Using Texture Analysis of Scanning Electron Microscopy Images

Polymer gels are regarded as a potential dosimeter for independent validation of absorbed doses in clinical radiotherapy. Several imaging modalities have been used to convert radiation-induced polymerization to absorbed doses from a macro-scale viewpoint. This study developed a novel dose conversion mechanism by texture analysis of scanning electron microscopy (SEM) images. The modified N-isopropyl-acrylamide (NIPAM) gels were prepared under normoxic conditions, and were administered radiation doses from 5 to 20 Gy. After freeze drying, the gel samples were sliced for SEM scanning with 50×, 500×, and 3500× magnifications. Four texture indices were calculated based on the gray level co-occurrence matrix (GLCM). The results showed that entropy and homogeneity were more suitable than contrast and energy as dose indices for higher linearity and sensitivity of the dose response curves. After parameter optimization, an R² value of 0.993 can be achieved for homogeneity using 500× magnified SEM images with 27 pixel offsets and no outlier exclusion. For dose verification, the percentage errors between the prescribed dose and the measured dose for 5, 10, 15, and 20 Gy were −7.60%, 5.80%, 2.53%, and −0.95%, respectively. We conclude that texture analysis can be applied to the SEM images of gel dosimeters to accurately convert micro-scale structural features to absorbed doses. The proposed method may extend the feasibility of applying gel dosimeters in the fields of diagnostic radiology and radiation protection.     

A Novel,Single Algorithm Approach to Predict Acenocoumarol Dose Based on CYP2C9 and VKORC1 Allele Variants

The identification of CYP2C9 and VKORC1 genes has strongly stimulated the research on pharmacogenetics of coumarins in the last decade. We assessed the combined influence of CYP2C9 *2 and *3, and VKORC1 c.-1639G>A, 497C>G, and 1173C>T variants, on acenocoumarol dosage using a novel algorithm approach, in 193 outpatients who had achieved stable anticoagulation. We constructed an “acenocoumarol-dose genotype score” (AGS, maximum score = 100) based on the number of alleles associated with higher acenocoumarol dosage carried by each subject for each polymorphism. The mean AGS was higher in the high-dose (>28mg/week) compared with the low-dose (<7mg/week) group (mean(SEM) of 84.1±3.4 vs. 62.2±4.8, P = 0.008). An AGS>70 was associated with an increased odds ratio (OR) of requiring high acenocoumarol dosage (OR: 3.347; 95%CI: 1.112–10.075; P = 0.032). In summary, although more research is necessary in other patient cohorts, and this algorithm should be replicated in an independent sample, our data suggest that the AGS algorithm could be used to help discriminating patients requiring high acenocoumarol doses to achieve stable anti-coagulation.     

基于互信息和自相关函数的睡眠期间心率变异性研究

目的：研究互信息和自相关函数在睡眠各阶段心率变异性（heart rate variability,HRV）分析中的应用。方法：采用网络公开数据库SleepHeart Rateand Stroke VolumeDataBarhk,将RR序列分为30S一段,并以每30S数据为中心截取5minRR序列作为待分析对象。提取5minRR序列的互信息特征BDM、PDM和自相关函数特征BDC、PDC,然后用统计方法分析各特征在觉醒瓜EM／浅睡／深睡四种睡眠状态下的差异。结果：浅睡和深睡期间,BDM、PDM显著高于觉醒和REM睡眠（P〈0．001）。而BDC显著低于觉醒和REM睡眠（P〈0．001）,PDC无显著差异（P〉0．05）。结论：①BDM、PDM和BDC从不同角度反映了不同睡眠阶段下RR序列的特征,它们或许与HRV不同的调节机制有关。@BDM、PDM和BDC可作为辅助HRV睡眠分期的新指标。