Invariant aphthovirus consensus nucleotide sequence in the transition to error catastrophe

RNA viruses replicate as complex distributions of non-identical but closely related variant genomes termed viral quasispecies. When the error rate during genome replication exceeds a threshold value, the genetic information cannot be maintained and the system enters error catastrophe. This violation of the error threshold results in virus extinction and it is currently being investigated as a new antiviral strategy, based on antiviral activity of some mutagenic agents. Previous studies with the important animal pathogen foot-and-mouth disease virus (FMDV) have shown that FMDV entry into error catastrophe is associated with an increase of complexity (mutation frequency and Shannon entropy) of the mutant spectrum of the quasispecies and that mutated, pre-extinction RNA interferes with the infectivity of standard RNA. Here, we report that despite the increase of complexity, the genomic consensus nucleotide sequence of pre-extinction FMDV RNA remains invariant, and that the fitness of pre-extinction FMDV is at least six-fold lower than the fitness of the parental viral clone, prior to mutagenic treatments. Thus, a low fitness genome ensemble can suppress replication of high fitness virus. Furthermore, the results show that profound genetic modifications associated with fitness decrease of a virus population can take place without any manifestation in the consensus genomic sequence. Thus, increase in mutant spectrum complexity and invariance of the consensus sequence characterizes FMDV extinction through error catastrophe.     

System weaknesses as contributing causes of accidents in health care.

OBJECTIVE: Accidents in health care, resulting in injury or death to the patient, are a matter of considerable concern. The aim of this study is to examine whether system weaknesses can contribute to these accidents, and if so, how. DESIGN: Eight consecutive accidents reported to the Health Authority in Sweden were analysed using MTO (Man-Technique-Organization) analysis. SETTING: Emergency care hospitals in Sweden. RESULTS: All cases that involved the system supported the assumption that system weaknesses are a contributing factor to accidents. In this study two types of latent failure could be identified: process control latent failures and interactional latent failures. The time span from activation of process control latent failures to operator error was very short, and the study demonstrates the simple relationship between situational factors and operator errors. Interactional latent failures exert system influence in a more indistinct manner. Latent failures, as seen in this study, act not only by creating opportunities for operator errors but also by hindering error detection in the time window available. Safety barriers, which might have prevented the accidents, could be proposed in seven out of eight cases. CONCLUSION: System weaknesses seem to play an important role in accident evolution. Consequently, certain measures can be suggested in order to improve patient safety: (i) sufficient resources should be allocated for research and development at both medical schools and hospitals in order to establish competence and procedures for systematic analyses of processes; and (ii) authorities handling accident cases should have adequate competence in system analysis.     

Cost analysis of different protocols for imaging a patient with acute flank pain

The aim of this study was to analyse the costs of different diagnostic approaches to patients with acute flank pain. Four different diagnostic approaches were considered: (a) spiral CT without contrast medium (CM); (b) plain film, ultrasonography (US) and intravenous urography (IVU) – the latter procedure is used in our department in cases still unsolved following the former investigations (28 % in our experience); (c) plain film, US and spiral CT without CM (as an alternative to IVU in 28 % of cases); and (d) IVU. The cost of each procedure in a university hospital was calculated, following analysis of the differential costs of each investigation (equipment, depreciation and maintenance costs, related materials and services, radiologists, radiographers, nurses) and their common costs (auxiliary personnel and indirect internal costs). Finally, we calculated the full cost of each procedure and applied it to the different diagnostic approaches. The full cost of each approach was: (a) spiral CT without CM = 74 Euro; (b) plain film, US and IVU (28 %) = 66.89 Euro; (c) plain film, US and spiral CT without CM (28 %) = 64.93 Euro; (d) IVU = 80.90 Euro. Intravenous urography alone or in unsolved cases is not to be considered because it provides higher costs and worse diagnostic results, whereas X-ray dose to patient is almost equal between IVU and spiral CT. Spiral CT integrated to plain film and US in unsolved cases could be preferred because of lower cost and dose to patient, though reaching a diagnostic conclusion may take longer than an immediate spiral CT. Received: 29 February 2000; Revised: 22 May 2000; Accepted: 23 May 2000     

脑血通颗粒剂定性定量分析

目的对脑血通颗粒剂进行定性定量分析。方法采用茚三酮、蒽醌定性反应和大黄素、补骨脂素、异补骨脂素薄层色谱鉴别进行定性控制;对补骨脂素、异补骨脂素应用高效液相色谱法定量测定;运用等离子发射光谱仪、氨基酸自动分析仪进行无机元素和氨基酸的测定。结果定性鉴别简便易行;含量测定方法中同分异构体补骨脂素、异补骨脂素分离较好,分离度大于2,补骨脂素、异补骨脂素柱效比较理想,理论塔板数均大于4000。结论此法分离效果好、重现性好、精密度高;元素分析和氨基酸分析结果可信度高,可用于脑血通颗粒剂的质量控制。     

主成分分析考察毛脉酸模最佳采收期

目的:分析不同生长发育期毛脉酸模中生物活性成分形成和积累规律,探索毛脉酸模采收期的选优方法,以确定最佳采收期。方法:采用HPLC,梯度洗脱,测定了2年生毛脉酸模不同生长发育期根中7种生物活性成分(白藜芦醇、白藜芦醇苷、大黄酚苷、酸模素、大黄素、大黄酚、大黄素甲醚)含量,对其进行主成分分析。结果:不同生长发育期采集的毛脉酸模中生物活性成分积累具有一定规律。结论:兼顾不同的治疗目的和含量因素,毛脉酸模的采收期以7月初为最佳。     

基于聚类分析的径向基神经网络用于证候诊断的研究

目的:优化中医证候诊断模型,为中医证候诊断标准的研究提供可行性方法.方法:提出用于中医证候诊断的径向基(Radial Basis Function,RBF)神经网络,利用聚类分析确定RBF神经网络隐层的参数,运用最小二乘确定RBF神经网络输出层的参数.结果:通过模型检验,证候诊断模型判准率比BP网络模型判准率高;证候诊断模型训练速度比BP网络模型快.结论:基于聚类分析的RBF神经网络用于中医证候诊断的研究是可行的和有效的.     

辨证掌握穴位注射方法提高穴位注射的疗效

目的:提高中西结合治疗疾病的疗效.方法:在中医辨证的基础上,在腧穴上进行针剂注射.结果:通过针刺和药液渗透,将穴位疗效和药理作用结合在一起,充分发挥其综合效能.结论:用中医辨证理论,穴位注射治疗能疏通经络,调补阴阳.针药结合,提高疗效.     

Population coding in spike trains of simultaneously recorded retinal ganglion cells

To achieve a better understanding of the parallel information processing that takes place in the nervous system, many researchers have recently begun to use multielectrode techniques to obtain high spatial- and temporal-resolution recordings of the firing patterns of neural ensembles. Apart from the complexities of acquiring and storing single unit responses from large numbers of neurons, the multielectrode technique has provided new challenges in the analysis of the responses from many simultaneously recorded neurons. This paper provides insights into the problem of coding/decoding of retinal images by ensembles of retinal ganglion cells. We have simultaneously recorded the responses of 15 ganglion cells to visual stimuli of various intensities and wavelengths and analyzed the data using discriminant analysis. Models of stimulus encoding were generated and discriminant analysis used to estimate the wavelength and intensity of the stimuli. We find that the ganglion cells we have recorded from are non-redundant encoders of these stimulus features. While single ganglion cells are poor classifiers of the stimulus parameters, examination of the responses of only a few ganglion cells greatly enhances our ability to specify the stimulus wavelength and intensity. Of the parameters studied, we find that the rate of firing of the ganglion cells provides the most information about these stimulus parameters, while the timing of the first action potential provides almost as much information. While we are not suggesting that the brain is using these variables, our results show how a population of sensory neurons can encode stimulus features and suggest that the brain could potentially deduce reliable information about stimulus features from response patterns of retinal ganglion cell populations.     

Barrier function of porcine choroid plexus epithelial cells is modulated by cAMP-dependent pathways in vitro

In the present paper, we demonstrate that the barrier properties of primary cultured epithelial cells isolated from porcine choroid plexus are regulated by cAMP-dependent signal transduction pathways in vitro. Triggering cAMP-connected cascades in cell layers grown on permeable filters with cAMP-analogues or forskolin led to a significant increase of transepithelial electrical resistances and a pronounced reduction in the permeation rate of a 4 kDa-dextran probe. In dose-response experiments using the cAMP-analogue 8-(4-chlorophenylthio)-cAMP transepithelial electrical resistances were observed to increase above a threshold concentration ranging between 10(-5.5) and 10(-5) M. Additional impedance studies performed with confluent cell layers grown on gold-film electrodes revealed that the observed changes in transepithelial resistances and presumably also in macromolecular permeation rates were not entirely caused by a reinforcement of intercellular junctions but also contained contributions from changes in the cell-substrate adhesion pattern. These inherent contributions to the electrical resistance and macromolecular permeability are caused by a restricted diffusion pathway between basal plasma membrane and culture substrate that have to be considered in data analysis, especially when leaky cell layers on filter substrates with low pore densities are used.