BACKGROUND & AIMS: :In this study, the efficiency of binary ethyleneimine (BEI) in combination with formaldehyde (FA) and glutaraldehyde (GTA) in inactivating the Indian FMDV vaccine strains is compared. The acceptable safety of virus inactivation was faster and the inactivation rates were increased many-folds with combination of inactivants than BEI alone. FMDV A was inactivated rapidly than the other two serotypes with BEI + FA combination. Inactivation plots were linear for all the serotypes irrespective of inactivation process. Further, the integrity studies on 146S using serotype specific ELISA indicated no significant change in the antigenic mass of all the serotypes throughout the inactivation process. However, the loss of 146S antigen occurred in the subsequent steps of downstream processing. Further, the studies on intactness of viral RNA using real time PCR indicated the amplification of 1D gene sequences in all the preparations of timed samples irrespective of serotypes/inactivation process. Further, inactivated virus preparation (146S) was more stable at lower temperatures for all the serotypes/inactivation process. Among the combinations of inactivants, BEI + FA out performed compared to BEI + GTA and BEI in terms of inactivation rates, 146S yield and its storage stability, irrespective of the serotypes.

背景与目标： : 在这项研究中，比较了二元乙烯亚胺 (BEI) 与甲醛 (FA) 和戊二醛 (GTA) 联合灭活印度FMDV疫苗株的效率。与单独使用灭活剂相比，灭活剂的可接受安全性更快，灭活率提高了许多倍。FMDV A比BEI FA组合的其他两种血清型迅速失活。与灭活过程无关，所有血清型的灭活图都是线性的。此外，使用血清型特异性ELISA对146S的完整性研究表明，在整个灭活过程中，所有血清型的抗原质量没有显著变化。然而，146S抗原的损失发生在下游处理的后续步骤中。此外，使用实时PCR对病毒RNA的完整性进行的研究表明，无论血清型/失活过程如何，在所有定时样品的制剂中都扩增了1D基因序列。此外，对于所有血清型/灭活过程，灭活病毒制剂 (146S) 在较低温度下更稳定。在灭活剂的组合中，与BEI GTA和BEI相比，BEI + FA在灭活率，146S产率及其储存稳定性方面进行了比较，而与血清型无关。

BACKGROUND & AIMS: :The annual cycle of phytoplankton biomass was followed in a eutrophic lake (Lake Aydat, Massif Central, France), using classic descriptors (biovolumes and chlorophyll a) as well as adenosine-5'-phosphate (ATP) levels. ATP is the metabolite indicating living biomass. ATP/Cell count and ATP/Chlorophyll a ratios were elevated due to the presence of heterotrophic organisms, such as several species of ciliates. The first ratio is greater than the second. The difference can be explained either by an underestimation of the nanoplankton fraction through the cell count method, or by a lack of sedimentation in the settling chambers used for counting cells.

背景与目标： : 使用经典的描述符 (生物体积和叶绿素a) 以及腺苷-5 '-磷酸 (ATP) 水平，在富营养化的湖泊 (法国中部Massif中部的Aydat湖) 中跟踪了浮游植物生物量的年度周期。ATP是指示活生物量的代谢产物。由于异养生物 (例如几种纤毛虫) 的存在，ATP/细胞计数和ATP/叶绿素a比率升高。第一个比率大于第二个比率。这种差异可以通过细胞计数方法低估了纳米浮游生物的比例，也可以通过用于计数细胞的沉降室中缺乏沉降来解释。

BACKGROUND & AIMS: :Surgeons, surgical nurses, and other operating room staff are exposed to airborne concentrations of methyl methacrylate during the preparation of orthopedic bone cement. Three sampling and analysis methods have been used to measurement methyl methacrylate in this work environment: (1) direct-reading photoacoustic infrared spectrometry, (2) solid sorbent and gas chromatography with flame ionization detection, and (3) colorimetric detector tubes. Previous studies have measured operating room exposures and judged the efficacy of cement mixing wth little, if any, regard for method sensitivity, detection limits, precision, or accuracy. The present investigation was designed to allow concurrent monitoring of methyl methacrylate levels from the same air volume using each of the three methods. Three popular orthopedic bone cement products were mixed during a number of repeat preparations (n = 36). Airborne concentrations were monitored concurrently during each preparation. Attention was given to the proper treatment of detection limits, and the results are reported both as raw data and descriptive statistics. A one-way ANOVA using a Tukey-Kramer HSD comparison was performed on method-specific results indicating that the photoacoustic infrared spectrometry and solid sorbent, gas chromatography with flame ionization detection are in good agreement, but the colorimetric detector tube method reports significantly different airborne concentrations. It is concluded that previous assessments using the photoacoustic infrared spectrometry and solid sorbent, gas chromatography with flame ionization detection may be relied on, but the detector tube method underreports actual exposures. Accordingly, the results of past exposure assessments and mixing method efficacy studies using colorimetric detector tubes may not be reliable.

背景与目标： : 外科医生，外科护士和其他手术室工作人员在准备骨科骨水泥期间暴露于空气中浓度的甲基丙烯酸甲酯。在此工作环境中，已使用三种采样和分析方法来测量甲基丙烯酸甲酯 :( 1) 直读光声红外光谱法，(2) 具有火焰离子化检测的固体吸附剂和气相色谱法，以及 (3) 比色检测器管。先前的研究已经测量了手术室的暴露，并判断了水泥混合的功效，如果有的话，则很少考虑方法的灵敏度，检出限，精密度或准确性。本研究旨在允许使用三种方法中的每种方法同时监测同一风量中的甲基丙烯酸甲酯水平。在许多重复准备过程中混合了三种流行的骨科骨水泥产品 (n = 36)。在每次准备过程中同时监测空气中的浓度。注意对检测限的正确处理，并将结果报告为原始数据和描述性统计。使用Tukey-Kramer HSD进行的单因素方差分析比较了方法的特异性结果，表明光声红外光谱法和固体吸附剂，气相色谱和火焰离子化检测法具有良好的一致性，但是比色检测器管法报告的空气浓度明显不同。结论是，可以依靠以前使用光声红外光谱法和固体吸附剂，气相色谱和火焰离子化检测进行的评估，但是检测器管方法低估了实际暴露。因此，使用比色检测器管的过去暴露评估和混合方法功效研究的结果可能不可靠。

BACKGROUND & AIMS: BACKGROUND:Informed consent in family planning includes knowledge of mechanism of action. Some methods of family planning occasionally work after fertilization. Knowing about postfertilization effects may be important to some women before choosing a certain family planning method. The objective of this survey is to explore women's attitudes towards postfertilization effects of family planning methods, and beliefs and characteristics possibly associated with those attitudes. METHODS:Cross-sectional survey in a sample of 755 potentially fertile women, aged 18-49, from Primary Care Health Centres in Pamplona, Spain. Participants were given a 30-item, self-administered, anonymous questionnaire about family planning methods and medical and surgical abortion. Logistic regression was used to identify variables associated with women's attitudes towards postfertilization effects. RESULTS:The response rate was 80%. The majority of women were married, held an academic degree and had no children. Forty percent of women would not consider using a method that may work after fertilization but before implantation and 57% would not consider using one that may work after implantation. While 35.3% of the sample would stop using a method if they learned that it sometimes works after fertilization, this percentage increased to 56.3% when referring to a method that sometimes works after implantation. Women who believe that human life begins at fertilization and those who consider it is important to distinguish between natural and induced embryo loss were less likely to consider the use of a method with postfertilization effects. CONCLUSION:Information about potential postfertilization effects of family planning methods may influence women's acceptance and choice of a particular family planning method. Additional studies in other populations are necessary to evaluate whether these beliefs are important to those populations.

背景与目标：

BACKGROUND & AIMS: :Over the past several years, multivariate approaches have been developed that address the problem of disease diagnosis. Here, we report an integrated approach to the problem of prognosis that uses protein microarrays to measure a focused set of molecular markers and non-parametric methods to reveal non-linear relationships among these markers, clinical variables, and patient outcome. As proof-of-concept, we applied our approach to the prediction of early mortality in patients initiating kidney dialysis. We found that molecular markers are not uniformly prognostic, but instead vary in their value depending on a combination of clinical variables. This may explain why reports in this area aiming to identify prognostic markers, without taking into account clinical variables, are either conflicting or show that markers have marginal prognostic value. Just as treatments are now being tailored to specific subsets of patients, our results show that prognosis can also benefit from a 'personalized' approach.

背景与目标： : 在过去的几年中，已经开发了解决疾病诊断问题的多变量方法。在这里，我们报告了一种针对预后问题的综合方法，该方法使用蛋白质微阵列来测量一组集中的分子标记物，以及非参数方法来揭示这些标记物，临床变量和患者预后之间的非线性关系。作为概念验证，我们将我们的方法应用于开始肾透析的患者的早期死亡率的预测。我们发现，分子标志物的预后并不一致，而是根据临床变量的组合而变化。这可以解释为什么在不考虑临床变量的情况下，旨在识别预后标志物的这一领域的报告存在冲突或表明标志物具有边际预后价值。就像现在针对特定的患者子集进行治疗一样，我们的结果表明，“个性化” 方法也可以使预后受益。

BACKGROUND & AIMS: :The development of the continuous circular capsulorhexis (CCC) technique has contributed significantly to the safety and effectiveness of cataract extraction and intraocular lens implantation. This technique facilitates every size of smooth, circular, capsular opening, and it produces a strong capsular rim that resists tearing even when stretched during lens material removal or lens implantation. Maintaining the general integrity of the eye and facilitating such procedures as hydrodissection, endolenticular phacoemulsification, capsule polishing, and safe lens implantation in both adults and children are some of the advantages of CCC. This procedure can be performed in several ways, and it has been proven to be consistently reproducible by experienced surgeons.

背景与目标： : 连续环形撕囊 (CCC) 技术的发展为白内障摘除和人工晶状体植入的安全性和有效性做出了重要贡献。这种技术有利于各种尺寸的光滑，圆形，囊状开口，并且它产生了强大的囊状边缘，即使在去除镜片材料或植入镜片的过程中拉伸，也可以抵抗撕裂。CCC的一些优点是，保持眼睛的整体完整性并促进诸如水解剖，晶状体内超声乳化，胶囊抛光和成人和儿童安全的晶状体植入等程序。此过程可以通过多种方式进行，并且已被经验丰富的外科医生证明是始终如一地可重复的。

BACKGROUND & AIMS: :Elucidating the molecular and neural basis of complex social behaviors such as communal living, division of labor and warfare requires model organisms that exhibit these multi-faceted behavioral phenotypes. Social insects, such as ants, bees, wasps and termites, are attractive models to address this problem, with rich ecological and ethological foundations. However, their atypical systems of reproduction have hindered application of classical genetic approaches. In this review, we discuss how recent advances in social insect genomics, transcriptomics, and functional manipulations have enhanced our ability to observe and perturb gene expression, physiology and behavior in these species. Such developments begin to provide an integrated view of the molecular and cellular underpinnings of complex social behavior.

背景与目标： : 阐明复杂社会行为 (例如公共生活，分工和战争) 的分子和神经基础，需要表现出这些多方面的行为表型的模型生物。社会昆虫，如蚂蚁、蜜蜂、黄蜂和白蚁，是解决这一问题的有吸引力的模型，具有丰富的生态和行为学基础。然而，它们的非典型繁殖系统阻碍了经典遗传方法的应用。在这篇综述中，我们讨论了社会昆虫基因组学，转录组学和功能操作的最新进展如何增强了我们观察和干扰这些物种的基因表达，生理和行为的能力。这样的发展开始提供复杂社会行为的分子和细胞基础的综合视图。

BACKGROUND & AIMS: :The width of retinal vessel images on fundus photographs was determined by projection micrometry and microdensitometry. These methods were evaluated on 12 retinal vessels using the negatives of 570-nm monochromatic fundus photographs. For projection micrometry, the intraobserver reproducibility of vessel width measurements was 1.6%-2.9%, depending upon the experience of the observer. Significant interobserver differences in the measured widths were demonstrated. For microdensitometry, three distinct measurement criteria were used. Significant differences in width as measured by the three criteria were found, but there were no interoperator differences for each criterion. The intraoperator reproducibility of vessel width measurements by microdensitometry was 2.1%-2.5%. Significant differences were found in the vessel widths determined by the micrometry and densitometry methods, and results obtained by micrometry are discussed in terms of edge-detection phenomena.

背景与目标： : 通过投影显微法和显微密度法确定眼底照片上视网膜血管图像的宽度。使用570 nm单色眼底照片的底片在12条视网膜血管上评估了这些方法。对于投影显微测量，根据观察者的经验，血管宽度测量的观察者内重现性为1.6%-2.9%。证明了观察者之间在测量宽度上的显着差异。对于显微光密度测定法，使用了三种不同的测量标准。通过三个标准测得的宽度存在显着差异，但是每个标准都没有算子间差异。通过显微密度测定法测量血管宽度的操作者内部可重复性为2.1%-2.5%。在通过显微法和光密度法确定的血管宽度中发现了显着差异，并根据边缘检测现象讨论了通过显微法获得的结果。

BACKGROUND & AIMS: :This paper examines the association between social networks and contraceptive use. Using data from a survey of women belonging to voluntary associations in Yaoundé, Cameroon, we find that the behavior and characteristics of the members of a respondent's personal networks are associated with her contraceptive use, over and above a set of her own individual characteristics that are usually found to be important. Respondents who report that their network partners approve of contraception, use it, and encourage the respondent to use are more likely to use contraception themselves; the association with encouragement is particularly strong. Moreover, there is a strong association between the specific methods of contraception used by a respondent and those used by her network partners, suggesting that members of personal networks exchange and evaluate specific methods. Because most of the respondent's network partners were interviewed, we are able to compare the respondent's perceptions of contraceptive use by her network partners with the network partner's actual use. We find that it is perceptions of use that matter, even if those perception are incorrect.

背景与目标： : 本文研究了社交网络与避孕药具使用之间的关联。使用来自喀麦隆雅温得自愿协会的妇女的调查数据，我们发现受访者个人网络成员的行为和特征与她的避孕药具使用有关，超出了她自己的一系列个人特征，通常被发现很重要。报告自己的网络伴侣赞成避孕，使用避孕并鼓励受访者使用避孕的受访者更有可能自己使用避孕措施; 与鼓励的联系特别强烈。此外，受访者使用的特定避孕方法与她的网络合作伙伴使用的避孕方法之间存在很强的联系，这表明个人网络成员交换和评估特定方法。由于大多数受访者的网络合作伙伴都接受了采访，因此我们能够将受访者对其网络合作伙伴使用避孕药具的看法与网络合作伙伴的实际使用情况进行比较。我们发现，重要的是对使用的感知，即使这些感知是不正确的。

BACKGROUND & AIMS: PURPOSE:Upper gastrointestinal bleeding (UGIB) is a severe and frequent drug-related event. In order to enable efficient drug safety alert generation in the French National Healthcare System database (SNDS), we assessed and calibrated empirically case-based designs to identify drug associated with UGIB risk. METHODS:All cases of UGIB were extracted from SNDS (2009-2014) using two definitions. Positive and negative drug controls were used to compare 196 self-controlled case series (SCCS), case-control (CC) and case-population (CP) design variants. Each variant was evaluated in a 1/10th population sample using area under the receiver operating curve (AUC) and mean square error (MSE). Parameters that had major impacts on results were identified through logistic regression. Optimal designs were replicated in the unsampled population. RESULTS:Using a specific UGIB definition, AUCs ranged from 0.64 to 0.80, 0.44 to 0.61 and 0.50 to 0.67, for SCCS, CC and CP, respectively. MSE ranged from 0.07 to 0.39, 0.83 to 1.33 and 1.96 to 4.6, respectively. Univariate regressions showed that high AUCs were achieved with SCCS with multiple drug adjustment and a 30-day risk window starting at exposure. The top-performing SCCS variant in the unsampled population yielded an AUC = 0.84 and MSE = 0.14, with 10/36 negative controls presenting significant estimates. CONCLUSIONS:SCCS adjusting for multiple drugs and using a 30-day risk window has the potential to generate UGIB-related alerts in the SNDS and hypotheses on its potential population impact. Negative control implementation highlighted that low systematic error was generated but that protopathic bias and confounding by indication remained unaddressed issues.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:The study was conducted to compare the antifertility effectiveness and side effects of the copper/low-density polyethylene nanocomposite IUD (experimental group) and the copper T220C IUD (control group). STUDY DESIGN:One hundred females were randomly divided into two groups (experimental group and control group, n = 50 in each group). Clinical observation and comparative study were performed on the two groups for 12 months. RESULTS:Follow-up rate was 100% at the 12th month. In the experimental group and control group, the cumulative continuation rates were both 92.0 per 100 women at the 12th month and there was no difference between them (p > .05). The pregnancy rate, removal rate and expulsion rate were low with the difference being not statistically significant (p>.05). The most common side effects were excessive menstrual bleeding, spotting and pain. The rates of side effects were lower in the experimental group than in control group, especially during the initial 3 months after insertion with the differences being statistically significant (p < .05). CONCLUSION:The new design of the copper/low-density polyethylene nanocomposite IUD showed low pregnancy rate, high contraceptive efficacy and satisfactory acceptability. The study suggested that the TCu220C IUD also had high contraceptive efficacy, but had relatively more side effects.

背景与目标：

BACKGROUND & AIMS: :An assessment of potential methods suitable for degradation and/or reduction of refractory organics was performed on landfill leachate from SYSAV AB, Malmö, Sweden. Pretreatment of the leachate was performed in a sequence batch reactor designed for nitrification in activated sludge. Oxidation of the leachate was then O3, O3/pH adjustment (pH 9 and 10), H2O2, O3/H2O2 and performic acid in lab-scale reactors. The degradation of organic material was followed with chemical oxygen demand (COD) measurements for all experiments except for the performic acid treatment for which total organic carbon (TOC) measurements were used. The potential degradation of refractory organics into biodegradable organic material was analysed by subsequent oxygen uptake rate (OUR) measurements in laboratory batch reactors. Ozonation of biologically pre-treated leachate increased reduction of the organic material. The most biodegradable organic material was produced after oxidation with only ozone and ozonation at pH 9. Performic acid did not reduce the content of organic material in the leachate. However, a combination of biological pretreatment, chemical oxidation with O3/H2O2 and a subsequent biological process resulted in the most efficient oxidation method for the tested leachate.

背景与目标： : 对瑞典马尔默SYSAV AB的垃圾填埋场渗滤液进行了适合降解和/或减少难降解有机物的潜在方法的评估。渗滤液的预处理是在设计用于活性污泥硝化的顺序分批反应器中进行的。然后在实验室规模的反应器中，渗滤液的氧化是O3，O3/pH调节 (pH 9和10)，H2O2，O3/H2O2和过甲酸。除使用总有机碳 (TOC) 测量的过甲酸处理外，所有实验均对有机材料的降解进行化学需氧量 (COD) 测量。通过随后在实验室间歇反应器中进行的氧气吸收率 (OUR) 测量，分析了难熔有机物可能降解为可生物降解的有机材料。生物预处理渗滤液的臭氧化增加了有机材料的减少。最可生物降解的有机材料是在仅用臭氧和臭氧化在pH 9下氧化后产生的。过甲酸不会降低渗滤液中有机物质的含量。然而，生物预处理，O3/H2O2的化学氧化以及随后的生物过程相结合，可以为测试的渗滤液提供最有效的氧化方法。

BACKGROUND & AIMS: :Clinical decision support systems are a combination of software techniques to help the clinicians in their medical decision making process via functionalities ranging from basic signal analysis to therapeutic planning and computerized guidelines. The algorithms providing all these functionalities must be very carefully validated on real patient data and must be confronted to everyday clinical practice. One of the main problems when developing these techniques is the difficulty to obtain high-quality complete patient records, comprising data coming both from the biomedical equipment (high-frequency signals), and from numerous other sources (therapeutics, imagery, clinical actions, etc.). In this paper, we present an infrastructure for developing and testing such software algorithms. It is based on a bedside workstation where testing different algorithms simultaneously on real-time data is possible in the ward. It is completed by a collaborative portal enabling different teams to test their software algorithms on the same patient records, making comparisons and cross-validations more easily.

背景与目标： : 临床决策支持系统是软件技术的组合，可通过从基本信号分析到治疗计划和计算机化指南的功能来帮助临床医生进行医疗决策。提供所有这些功能的算法必须在真实的患者数据上进行非常仔细的验证，并且必须面对日常临床实践。开发这些技术时的主要问题之一是难以获得高质量的完整患者记录，包括来自生物医学设备 (高频信号) 和来自许多其他来源 (治疗，图像，临床动作等) 的数据。在本文中，我们介绍了用于开发和测试此类软件算法的基础结构。它基于床边工作站，可以在病房中同时测试实时数据的不同算法。它由一个协作门户网站完成，使不同的团队能够在相同的患者记录上测试他们的软件算法，从而更容易进行比较和交叉验证。

BACKGROUND & AIMS: :Currently developed progesterone receptor modulators (PRMs) are steroid-derived compounds with mild or potent antiprogestin activity. PRMs may exert a contraceptive activity by different mechanisms such as blockade of ovulation and endometrial desynchronization. Their potential clinical applications are manifold and are very promising in major public health areas, including emergency contraception, long term oestrogen-free contraception (administered alone, or in association with a progestin-only pill to improve bleeding patterns), endometriosis and myoma treatment. The mechanisms of their anti-ovulatory effects and of the endometrial modifications elicited during long term PRM treatment are still not fully elucidated. In future clinical applications, PRMs will be administered orally, via intrauterine systems or vaginal rings.

背景与目标： : 目前开发的孕激素受体调节剂 (prm) 是具有温和或有效抗孕激素活性的类固醇衍生化合物。PRMs可能通过不同的机制 (例如排卵阻断和子宫内膜失步) 发挥避孕活性。它们的潜在临床应用是多方面的，并且在主要公共卫生领域非常有前途，包括紧急避孕，长期无雌激素避孕 (单独使用或与仅孕激素药联合使用以改善出血模式)，子宫内膜异位症和肌瘤治疗。在长期PRM治疗期间，其抗排卵作用和子宫内膜修饰的机制仍未完全阐明。在未来的临床应用中，PRMs将通过宫内系统或阴道环口服。

BACKGROUND & AIMS: :Different methods of telomere length measurement are used to identify patients with telomeropathies. In our lab, we established four different methods for telomere length measurement, terminal restriction fragment (TRF) analysis by Southern blot analysis, quantitative PCR (qPCR), quantitative telomere/centromere fluorescence in situ hybridization (T/C-FISH) and fluorescence in situ hybridization combined with flow cytometry (FlowFISH). The methods each have distinct properties and apart from this-according to our experience and data-may have an impact on the individual result. In this study, we therefore compared and validated these methods measuring 154 healthy individuals of different age groups (newborn-81 years). A linear decline was found for every method (Southern blotting 64 bp per year; qPCR 31 bp per year; T/C-FISH 36 bp per year; FlowFISH 50 bp per year). With the equation of the regression line the values of each method (T/S ratio, T/C value, RTL value) can be expressed in absolute kb. All methods showed acceptable accuracy. The analysis indicated good agreement between all methods, with the best agreement between T/C-FISH and FlowFISH. Here, FlowFISH was the most precise, accurate, and reproducible method compared to the other methods. Based on our data, we emphasize the influence of expertise and experience that is required to produce robust and reliable telomere length analyses. Furthermore, we want to provide the scientific community working in diagnostics and research with data-funded advice on how to choose the appropriate method to safely discriminate between natural variability and pathological telomere shortening in individual cases.

背景与目标： : 不同的端粒长度测量方法用于识别端粒病患者。在我们的实验室中，我们建立了四种不同的端粒长度测量方法，通过Southern印迹分析，定量PCR (qPCR)，端粒/着丝粒荧光原位杂交 (T/C-FISH) 和荧光原位杂交结合流式细胞仪 (FlowFISH) 分析末端限制性片段 (TRF)。根据我们的经验和数据，每种方法都具有不同的属性，除此之外，可能会对单个结果产生影响。因此，在这项研究中，我们比较并验证了这些方法，这些方法测量了154个不同年龄组 (新生儿-81岁) 的健康个体。每种方法均呈线性下降 (每年Southern印迹64 bp; 每年qPCR 31 bp; 每年T/C-FISH 36 bp; 每年FlowFISH 50 bp)。利用回归线的方程，每种方法的值 (T/S比，T/C值，RTL值) 都可以用绝对kb表示。所有方法均显示出可接受的准确性。分析表明所有方法之间具有良好的一致性，T/C-鱼和FlowFISH之间具有最佳的一致性。与其他方法相比，FlowFISH是最精确，准确和可重现的方法。根据我们的数据，我们强调产生可靠而可靠的端粒长度分析所需的专业知识和经验的影响。此外，我们希望为从事诊断和研究的科学界提供数据资助的建议，以了解如何选择适当的方法来安全地区分个别情况下的自然变异性和病理性端粒缩短。