Estimating Temporal Transmission Parameters from Infectious Disease Household Data, with Application to Taiwan SARS Data

Taking households having at least one infective as standard units and considering both a within-household infection rate and a global infection rate, we propose a Bayesian two level mixing S-I-R (susceptible-infective-removed) counting process model in which the transmission parameters may change over time and the parameters of interest are the within-household infection rate and the removal rate. Customized Markov chain Monte Carlo methods are developed for generating samples from the posterior distribution for inference purpose, based only on the removal times. The numerical performance of this method is examined in a simulation study. Applying this method to 2003 Taiwan SARS data, we find that the within-household infection rate decreases, the removal rate increases and their ratio is less than one and decreases significantly during the epidemic. This method allows the estimation of these parameters during the epidemic. For a rapidly transmitted disease, it provides a method to nearly real-time tracking of infection measures.     

Spreadsheet Method for Evaluation of Biochemical Reaction Rate Coefficients and Their Uncertainties by Weighted Nonlinear Least-Squares Analysis of the Integrated Monod Equation

A convenient method for evaluation of biochemical reaction rate coefficients and their uncertainties is described. The motivation for developing this method was the complexity of existing statistical methods for analysis of biochemical rate equations, as well as the shortcomings of linear approaches, such as Lineweaver-Burk plots. The nonlinear least-squares method provides accurate estimates of the rate coefficients and their uncertainties from experimental data. Linearized methods that involve inversion of data are unreliable since several important assumptions of linear regression are violated. Furthermore, when linearized methods are used, there is no basis for calculation of the uncertainties in the rate coefficients. Uncertainty estimates are crucial to studies involving comparisons of rates for different organisms or environmental conditions. The spreadsheet method uses weighted least-squares analysis to determine the best-fit values of the rate coefficients for the integrated Monod equation. Although the integrated Monod equation is an implicit expression of substrate concentration, weighted least-squares analysis can be employed to calculate approximate differences in substrate concentration between model predictions and data. An iterative search routine in a spreadsheet program is utilized to search for the best-fit values of the coefficients by minimizing the sum of squared weighted errors. The uncertainties in the best-fit values of the rate coefficients are calculated by an approximate method that can also be implemented in a spreadsheet. The uncertainty method can be used to calculate single-parameter (coefficient) confidence intervals, degrees of correlation between parameters, and joint confidence regions for two or more parameters. Example sets of calculations are presented for acetate utilization by a methanogenic mixed culture and trichloroethylene cometabolism by a methane-oxidizing mixed culture. An additional advantage of application of this method to the integrated Monod equation compared with application of linearized methods is the economy of obtaining rate coefficients from a single batch experiment or a few batch experiments rather than having to obtain large numbers of initial rate measurements. However, when initial rate measurements are used, this method can still be used with greater reliability than linearized approaches.     

On the analysis of evolutionary change along single branches in a phylogeny

Comparative biologists are sometimes interested in estimating the evolutionary rate along single branches in a phylogeny. I evaluate two methods by which the evolutionary rate along single branches can be compared with the evolutionary rate throughout the rest of the tree. The first is McPeek's contrasts method, and the second is a likelihood method presented independently in two recently published studies. Although the latter method was developed primarily for the comparison of rates among clades, the approach is equally suited for the analysis of evolutionary rate along single or isolated branches. I find that Type I error is acceptable in both methods but that power and parameter estimation are relatively poor in McPeek's method as it is typically applied.     

Evaluation of a model for seeded isothermal batch protein crystallization

Bulk protein crystallization, unlike small molecule crystallization, has found very limited use in biopharmaceutical manufacture. Most work in this area targets obtaining single large crystals for molecular structure determination by crystallography. Design and optimization of bulk crystallization for protein recovery and purification is much less common, and requires a mathematical model for analysis of laboratory data suitable for scale-up purposes. Traditionally, the crystal size distribution and method of moments is used to characterize the crystallization process. A simpler method is presented in this paper that utilizes the desupersaturation curve. The method uses an approach that does not require expensive instrumentation or characterization of the seed crystal size distribution. The method is extended to allow determination of both the mass deposition rate constant and the growth rate order from a single desuperaturation curve. Experimental data for the bulk crystallization of ovalbumin are used to validate the method. The rate constants and rate order obtained using the new method compare well with literature values. Scale-up is illustrated by prediction of the impact of changes in seed mass on protein crystallization. This new method offers a straightforward and low-cost alternative to traditional methods for the analysis and scale-up of protein crystallization data.     

Detection of endometrial cancer by flow cytometry using two monoclonal antibodies.

BACKGROUND: To develop a supplementary diagnostic method for endometrial cancer by measuring the reactivity of various endometrial lesions with two monoclonal antibodies. METHODS: We investigated the reactivity of various endometrial lesions with two monoclonal antibodies (MSN-1 and MSN-3) by flow cytometry (one-color and two-color methods). RESULTS: The two-color method appeared to be suitable for use in place of simultaneous performance of the one-color methods with MSN-1 and MSN-3. The positivity rate for normal endometrium was 16.0% with the two-color method, which was lower than the rate of 30.0% obtained with concomitant used of the one-color methods. The positivity rate for endometrial cancer was high, 84.0%, with the two-color method. The positivity rate was 85.7% for well-differentiated endometrial cancer, 71.4% for moderately differentiated cancer, and 100.0% for poorly differentiated cancer; thus, the rate was high irrespective of the cellular differentiation. CONCLUSIONS: The two-color method is more useful than the one-color method as a supplementary diagnostic procedure for endometrial cancer.     

对比不同静脉放血方法治疗真性红细胞增多症的临床效果*

摘要目的：观察四种不同的静脉放血方法治疗真性红细胞增多症的临床疗效,对比分析不同疗法所用的时间及管道填塞率,从 而探讨治疗真性红细胞增多症的有效方法。方法：选取2009 年5 月至2012 年5 月我院收治的真性红细胞增多症患者50 名,随机 采取密闭式放血袋法、注射器法、胃肠减压器法和球形负压引流袋法对上述患者进行治疗,观察并比较不同方法治疗的过程中, 患者管道的填塞率及操作时间。结果：密闭式放血袋法在放血过程中穿刺成功率高,操作时间短,管道的填塞率低。结论：密闭式 放血袋操作简便,省时、省力、无并发症发生,可在临床广泛推广使用。     

Indirect Estimates of Total Fertility Rate Using Child Woman/Ratio: A Comparison with the Bogue-Palmore Method

Indirect estimation methodologies of the total fertility rate (TFR) have a long history within demography and have provided important techniques applied demographers can use when data is sparse or lacking. However new methodologies for approximating the total fertility rate have not been proposed in nearly 30 years. This study presents a novel method for indirectly approximating the total fertility rate using an algebraic rearrangement of the general fertility rate (GFR) through the known relationship between GFR and TFR. It then compares the proposed method to the well-known Bogue-Palmore method. These methods are compared in 196 countries and include overall errors as well as characteristics of the countries that contribute to fertility behavior. Additionally, these methods were compared geographically to find any geographical patterns. We find this novel method is not only simpler than the Bogue-Palmore method, requiring fewer data inputs, but also has reduced algebraic and absolute errors when compared with the Bogue-Palmore method and specifically outperforms the Bogue-Palmore method in developing countries. We find that our novel method may be useful estimation procedure for demographers.     

Paraquat Prohibition and Change in the Suicide Rate and Methods in South Korea

The annual suicide rate in South Korea is the highest among the developed countries. Paraquat is a highly lethal herbicide, commonly used in South Korea as a means for suicide. We have studied the effect of the 2011 paraquat prohibition on the national suicide rate and method of suicide in South Korea. We obtained the monthly suicide rate from 2005 to 2013 in South Korea. In our analyses, we adjusted for the effects of celebrity suicides, and economic, meteorological, and seasonal factors on suicide rate. We employed change point analysis to determine the effect of paraquat prohibition on suicide rate over time, and the results were verified by structural change analysis, an alternative statistical method. After the paraquat prohibition period in South Korea, there was a significant reduction in the total suicide rate and suicide rate by poisoning with herbicides or fungicides in all age groups and in both genders. The estimated suicide rates during this period decreased by 10.0% and 46.1% for total suicides and suicides by poisoning of herbicides or fungicides, respectively. In addition, method substitution effect of paraquat prohibition was found in suicide by poisoning by carbon monoxide, which did not exceed the reduction in the suicide rate of poisoning with herbicides or fungicides. In South Korea, paraquat prohibition led to a lower rate of suicide by paraquat poisoning, as well as a reduction in the overall suicide rate. Paraquat prohibition should be considered as a national suicide prevention strategy in developing and developed countries alongside careful observation for method substitution effects.     

Accounting for gene rate heterogeneity in phylogenetic inference

Traditionally, phylogenetic analyses over many genes combine data into a contiguous block. Under this concatenated model, all genes are assumed to evolve at the same rate. However, it is clear that genes evolve at very different rates and that accounting for this rate heterogeneity is important if we are to accurately infer phylogenies from heterogeneous multigene data sets. There remain open questions regarding how best to incorporate gene rate parameters into phylogenetic models and which properties of real data correlate with improved fit over the concatenated model. In this study, two methods of accounting for gene rate heterogeneity are compared: the n-parameter method, which allows for each of the n gene partitions to have a gene rate parameter, and the alpha-parameter method, which fits a distribution to the gene rates. Results demonstrate that the n-parameter method is both computationally faster and in general provides a better fit over the concatenated model than the alpha-parameter method. Furthermore, improved model fit over the concatenated model is highly correlated with the presence of a gene with a slow relative rate of evolution.     

对比不同静脉放血方法治疗真性红细胞增多症的临床效果

目的：观察四种不同的静脉放血方法治疗真性红细胞增多症的临床疗效,对比分析不同疗法所用的时间及管道填塞率,从而探讨治疗真性红细胞增多症的有效方法。方法：选取2009年5月至2012年5月我院收治的真性红细胞增多症患者50名,随机采取密闭式放血袋法、注射器法、胃肠减压器法和球形负压引流袋法对上述患者进行治疗,观察并比较不同方法治疗的过程中,患者管道的填塞率及操作时间。结果：密闭式放血袋法在放血过程中穿刺成功率高,操作时间短,管道的填塞率低。结论：密闭式放血袋操作简便,省时、省力、无并发症发生,可在临床广泛推广使用。     

A pseudo-exponential feeding method for control of specific growth rate in fed-batch cultures

A simple feeding method for controlling specific growth rate in fed-batch culture was developed. This method applies a constant feed rate using a concentrate reservoir and two mixing chambers in series to simulate the exponential feeding. Fed-batch cultures with Escherichia coli showed that the present feeding method could sustain the cells growing at predetermined specific growth rates, where the time length for exponential growth was dependent on the magnitude of the growth rate. The present feeding method is convenient to operate, requires no computerized control equipments, and thus could expect an extensive application in fed-batch culture.     

Determination of rate constants for the reaction of hydroxyl radicals with some purines and pyrimidines using sunlight

Sunlight mediated hydroxyl radical production from aqueous ferric perchlorate at low pH has been investigated using deoxyribose-thiobarbituric acid assay. The rate of production of hydroxyl radical was found to be dependent on the time of irradiation. Hydroxyl radical scavengers can compete with deoxyribose for hydroxyl radicals produced in the system leading to a decreased yield of thiobarbituric acid chromogen. The second-order rate constants of the added scavengers can be determined using a simple competition kinetic method. The rate constants for the reaction of hydroxyl radical with a number of purine and pyrimidine derivatives were determined using this method. The rate constants obtained (1-7 x 10(9) dm(3) mol(-1) s(-1)) were found to be in good agreement with those reported using pulse radiolysis technique. The rate constants of dimethyluracil, xanthosine, amino and methyl substituted pyrimidines, cytidine monophosphate and uridine monophosphate were also determined by this method. It is proposed that sunlight mediated production of hydroxyl radical coupled with deoxyribose-thiobarbituric acid assay is a simple and efficient method for the determination of rate constants for the reaction of hydroxyl radical with a wide range of biomolecules.     

猪卵母细胞体外成熟的发育潜力及核移植重构胚构建方法的研究

为了提高猪体细胞核移植重构胚发育潜力,本研究对体外成熟28 h、32 h、36 h、40 h、44 h、48 h、52 h和56 h的猪卵母细胞分别进行去核构建重构胚.研究结果表明,成熟44 h的卵母细胞核移植后有较高的融合率(58.99%)、卵裂率(67.52%)和囊胚率(22.78%),而成熟48 h的卵母细胞则分别为56.51%、65.73%和15.96%;且卵龄为44 h的卵母细胞核移植后分裂率与囊胚率显著高于卵龄为40 h、36 h、32 h、28 h的卵母细胞的分裂率与囊胚率(P＜0.05).卵龄为48 h的卵母细胞融合率高于卵龄为52 h卵母细胞的融合率(P＜0.05).同时我们还探讨了不同去核方法(盲吸法、Hochest33342染色法和Spindle-view system)对猪体细胞核移植重构胚发育能力的影响.研究结果发现,盲吸法、Hoechest33342染色法和Spindle-view system法的去核率分别达到76.33%,100.00%和98.40%.Hoechest染色法去核率显著高于盲吸法的去核率(P＞0.05),而与Spindle-view法去核率没有差异(P＞0.05).三种方法在融合率和囊胚率方面差异不显著(P＞0.05),但Hoechest染色法的分裂率较低,差异显著(P＜0.05).进一步的研究表明,细胞质内注射进行核移植构建重构胚的分裂率和囊胚率分别为68.13%和6.44%;透明带下注射法则为60.37%和8.08%,两者差异不显著(P＜0.05);两者均可运用于猪体细胞的核移植,这为建立有效的猪体细胞核移植体系提供了参考.     

A new method with flexible and balanced control of false negatives and false positives for hit selection in RNA interference high-throughput screening assays

The z-score method and its variants for testing mean difference are commonly used for hit selection in high-throughput screening (HTS) assays. Strictly standardized mean difference (SSMD) offers a way to measure and classify the short interfering RNA (siRNA) effects. In this article, based on SSMD, the authors propose a new testing method for hit selection in RNA interference (RNAi) HTS assays. This SSMD-based method allows the differentiation between siRNAs with large and small effects on the assay output and maintains flexible and balanced control of both the false-negative rate, in which the siRNAs with strong effects are not selected as hits, and the restricted false-positive rate, in which the siRNAs with weak or no effects are selected as hits. This method directly addresses the size of siRNA effects represented by the strength of difference between an siRNA and a negative reference, whereas the classic z-score method and t-test of testing no mean difference address whether the mean of an siRNA is exactly the same as the mean of a negative reference. This method can readily control the false-negative rate, whereas it is nontrivial for the classic z-score method and t-test to control the false-negative rate. Therefore, theoretically, the SSMD-based method offers better control of the sizes of siRNA effects and the associated false-positive and false-negative rates than the commonly used z-score method and t-test for hit selection in HTS assays. The SSMD-based method should generally be applicable to any assay in which the end point is a difference in signal compared to a reference sample, including those for RNAi, receptor, enzyme, and cellular function.     

Improved estimates of environmental copper release rates from antifouling products

The US Navy Dome method for measuring copper release rates from antifouling paint in-service on ships' hulls can be considered to be the most reliable indicator of environmental release rates. In this paper, the relationship between the apparent copper release rate and the environmental release rate is established for a number of antifouling coating types using data from a variety of available laboratory, field and calculation methods. Apart from a modified Dome method using panels, all laboratory, field and calculation methods significantly overestimate the environmental release rate of copper from antifouling coatings. The difference is greatest for self-polishing copolymer antifoulings (SPCs) and smallest for certain erodible/ablative antifoulings, where the ASTM/ISO standard and the CEPE calculation method are seen to typically overestimate environmental release rates by factors of about 10 and 4, respectively. Where ASTM/ISO or CEPE copper release rate data are used for environmental risk assessment or regulatory purposes, it is proposed that the release rate values should be divided by a correction factor to enable more reliable generic environmental risk assessments to be made. Using a conservative approach based on a realistic worst case and accounting for experimental uncertainty in the data that are currently available, proposed default correction factors for use with all paint types are 5.4 for the ASTM/ISO method and 2.9 for the CEPE calculation method. Further work is required to expand this data-set and refine the correction factors through correlation of laboratory measured and calculated copper release rates with the direct in situ environmental release rate for different antifouling paints under a range of environmental conditions.     

吲哚菁绿联合亚甲蓝在乳腺癌前哨淋巴结活检中的临床应用

目的:探讨吲哚菁绿(indocyanine green,ICG)联合亚甲蓝在乳腺癌前哨淋巴结活检(sentinel lymph node biopsy,SLNB)中的临床应用价值。方法:共入组39例乳腺癌患者,在光学分子影像手术导航系统(surgical navigation system,SNS)的引导下,使用ICG联合亚甲蓝实施SLNB。快速冰冻病理证实前哨淋巴结(sentinel lymph node,SLN)转移者,即刻行腋窝淋巴结清扫(axillary lymph node dissection,ALND);SLN阴性者免于ALND。结果:联合法实施SLNB检出率95%,成功检出SLN125个,平均检出3.2个SLN,准确率95.0%,灵敏度100%,假阴性率0%;蓝染法检出率87.2%,成功检出SLN71个,平均检出1.8个SLN,准确率89.7%,灵敏度93.7%,假阴性率为6.3%;统计结果采用x2检验,检验结果具有统计学意义。结论:ICG联合亚甲蓝实施乳腺癌SLNB成功率高,假阴性率低,临床效果不亚于亚甲蓝,是实施SLNB的新方法。     

Multilocus estimation of selfing and its heritability

We describe a new method of estimating the selfing rate (S) in a mixed mating population based on a population structure approach that accounts for possible intergenerational correlation in selfing rate, giving rise to an estimate of the upper limit for heritability of selfing rate (h(2)). A correlation between generations in selfing rate is shown to affect one- and two-locus probabilities of identity by descent. Conventional estimates of selfing rate based on a population structure approach are positively biased by intergenerational correlation in selfing. Multilocus genotypes of individuals are used to give maximum-likelihood estimates of S and h(2) in the presence of scoring artifacts. Our multilocus estimation of selfing rate and its heritability (MESH) method was tested with simulated data for a range of conditions. Selfing rate estimates from MESH have low bias and root mean squared error, whereas estimates of the heritability of selfing rate have more uncertainty. Increasing the number of individuals in a sample helps to reduce bias and root mean squared error more than increasing the number of loci of sampled individuals. Improved estimates of selfing rate, as well as estimates of its heritability, can be obtained with this method, although a large number of loci and individuals are needed to achieve best results.     

A Monte Carlo simulation of chemical reactions

A computer-based algorithm to solve complex chemical rate equations is introduced. A simple Monte Carlo sampling method is used to generate chemical reactions in numbers proportional to reaction probabilities, and a second-order Runge-Kutta method is used to calculate time. The method is compared with a closed form mathematical solution for a simple chemical system, and it is compared with a numerical integration of the rate equations for a more complicated system.     

A theory for the estimation of DNA synthesis rates by flow cytometry

A method is presented for estimating the rate of DNA synthesis of a cell population by examining the DNA histogram generated by flow cytometry (FCM). The model is based on the use renewal equations to estimate the steady-state fraction of cells in each DNA compartment. The fraction of cells in each compartment is shown to be related to the Laplace transform of the transit time through that compartment. Two methods are introduced for estimating the rate of DNA synthesis utilizing different transit time distributions. One method is shown to be a simplification of the method of Dean and Anderson. The other method allows for variability in the DNA synthesis rate. The effects of quiescent cells are considered and attention is paid to the various assumptions underlying the estimation.     

Identification of genes with fast-evolving regions in microbial genomes

Complete sequences of multiple strains of the same microbial species provide an invaluable source for studying the evolutionary dynamics between orthologous genes over a relatively short time scale. Usually the intensity of the selection pressure is inferred from a comparison between the nonsynonymous substitution rate and the synonymous substitution rate. In this paper, we propose an alternative method for detecting genes with one or more fast-evolving regions from pairwise comparisons of orthologous genes. Our method looks for regions with overrepresented nonsynonymous mutations along the alignment, and requires a higher nonsynonymous evolution rate in those regions than the neutral evolution rate. It identifies gene targets under intensive selection pressure that are not detected from the conventional rate comparison analysis. For those identified genes with known annotations, most of them have a clear role in processes such as bacterial defense and host–pathogen interactions. Gene sets reported from our method provide a measure of the phenotypic divergence between two closely related genomes.