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1.
Vianna EO  García CA  Bettiol H  Barbieri MA  Rona RJ 《Allergy》2007,62(10):1146-1151
BACKGROUND: An asthma score was proposed in the European Community Respiratory Health Survey (ECRHS) framework, as dichotomous definitions could be less appropriate in the study of chronic diseases. The aims of this study were to assess the value of this asthma score in comparison with other definitions of asthma in another population setting, using as criteria bronchial hyperresponsiveness (BHR) to methacholine and diagnosed asthma, and the association of these definitions to known risk factors of asthma. METHODS: We used the ECRHS questionnaire on 2063 Brazilians, aged 23-25 years, and measured their BHR. We assessed the positive and negative likelihood ratios (PLR and NLR) of the asthma score (0-8), a three question score (ECRHS definition) and single asthma symptoms in relation to BHR and diagnosed asthma. RESULTS: The PLR were relatively low for all asthma definitions with odd ratios varying from 1.47 for asthma score to 5.50 for wheeze and waking with breathlessness without a cold. The NLR were near 1. The PLR were lower for assessments using the score than for dichotomous assessments or the ECRHS definition. The PLR increased with asthma scores, but the prevalence with higher scores was too low for useful analysis. The asthma score was slightly better for identifying associations from a set of known risk factors than the other two approaches. CONCLUSION: Our study provided little support for a greater validity of this asthma score over other asthma definitions, and only marginal advantage for identifying risk factors.  相似文献   

2.
    
It is believed that rare variants play an important role in human phenotypes; however, the detection of rare variants is extremely challenging due to their very low minor allele frequency. In this paper, the likelihood ratio test (LRT) and restricted likelihood ratio test (ReLRT) are proposed to test the association of rare variants based on the linear mixed effects model, where a group of rare variants are treated as random effects. Like the sequence kernel association test (SKAT), a state‐of‐the‐art method for rare variant detection, LRT and ReLRT can effectively overcome the problem of directionality of effect inherent in the burden test in practice. By taking full advantage of the spectral decomposition, exact finite sample null distributions for LRT and ReLRT are obtained by simulation. We perform extensive numerical studies to evaluate the performance of LRT and ReLRT, and compare to the burden test, SKAT and SKAT‐O. The simulations have shown that LRT and ReLRT can correctly control the type I error, and the controls are robust to the weights chosen and the number of rare variants under study. LRT and ReLRT behave similarly to the burden test when all the causal rare variants share the same direction of effect, and outperform SKAT across various situations. When both positive and negative effects exist, LRT and ReLRT suffer from few power reductions compared to the other two competing methods; under this case, an additional finding from our simulations is that SKAT‐O is no longer the optimal test, and its power is even lower than that of SKAT. The exome sequencing SNP data from Genetic Analysis Workshop 17 were employed to illustrate the proposed methods, and interesting results are described.  相似文献   

3.
    
It has been shown that it is preferable to use a robust model that incorporated constraints on the genotype relative risk rather than rely on a model that assumes the disease operates in a recessive or dominant fashion. Previous methods are applicable to case-control studies, but not to family based studies of case children along with their parents (triads). We show here how to implement analogous constraints while analyzing triad data. The likelihood, conditional on the parents genotype, is maximized over the appropriately constrained parameter space. The asymptotic distribution for the maximized likelihood ratio statistic is found and used to estimate the null distribution of the test statistics. The properties of several methods of testing for association are compared by simulation. The constrained method provides higher power across a wide range of genetic models with little cost when compared to methods that restrict to a dominant, recessive, or multiplicative model, or make no modeling restriction. The methods are applied to two SNPs on the methylenetetrahydrofolate reductase ( MTHFR ) gene with neural tube defect (NTD) triads.  相似文献   

4.
肌电假肢利用残肢残存肌肉的肌电信号实行对假肢的控制。对于低信噪比的残肢表面肌电,本研究采用广义似然比检测方法判断肌肉收缩起始时刻,其中判别阈值与肌电信号信噪比有关。针对不同信噪比的模拟肌电信号,采用离线仿真方法得到肌肉收缩起始时刻检测误差最小的判别阈值,得到信噪比-经验阈值拟合曲线,确定信噪比与阈值的对应关系;根据肌电信噪比由阈值拟合曲线得到判别阈值,采用似然比检测算法在线分析肌肉收缩的起始时刻。与传统算法比较,对于模拟肌电信号,本算法误差均值和标准差分别减小35%和43%;对于真实肌电信号,误差均值和标准差分别减少29%和23%。可见在小信噪比条件下广义似然比检测算法判断肌肉收缩起始时刻较传统算法更为准确。  相似文献   

5.
    
This paper concerns several important points when testing for Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium (LD) in genetics. First, we challenge the necessity of using exclusively two-sided tests for LD. Next, we show that the exact 2-sided tests based on the most popular measures of LD are not equivalent, and neither are the standard statistical tests even though the 1-sided tests are equivalent. We show how this results in different inference about LD for two data sets consisting of small groups of markers. Finally, we advocate the use of the conditional p-value for both LD and HWE testing. An important advantage of this p-value is that equivalent 1-sided tests are transformed into equivalent 2-sided tests.  相似文献   

6.
    
In the case‐parents design for testing candidate‐gene association, the conditional likelihood method based on genotype relative risks has been developed recently. A specific relation of the genotype relative risks is referred to as a genetic model. The efficient score tests have been used when the genetic model is correctly specified under the alternative hypothesis. In practice, however, it is usually not able to specify the genetic model correctly. In the latter situation, tests such as the likelihood ratio test (LRT) and the MAX3 (the maximum of the three score statistics for dominant, additive, and recessive models) have been used. In this paper, we consider the restricted likelihood ratio test (RLRT). For a specific genetic model, simulation results demonstrate that RLRT is asymptotically equivalent to the score test, and both are more powerful than the LRT. When the genetic model cannot be correctly specified, the simulation results show that RLRT is most robust and powerful in the situations we studied. MAX3 is the next most robust and powerful test. The TDT is the easiest statistic to compute, compared to MAX3 and RLRT. When the recessive model can be eliminated, it is also as robust and powerful as RLRT for other genetic models.  相似文献   

7.
    
Mutations in the RB1 gene are associated with retinoblastoma, which has served as an important model for understanding hereditary predisposition to cancer. Despite the great scrutiny that RB1 has enjoyed as the prototypical tumor suppressor gene, it has never been the object of a comprehensive survey of sequence variation in diverse human populations and primates. Therefore, we analyzed the coding (2,787 bp) and adjacent intronic and untranslated (7,313 bp) sequences of RB1 in 137 individuals from a wide range of ethnicities, including 19 Asian Indian hereditary retinoblastoma cases, and five primate species. Aside from nine apparently disease-associated mutations, 52 variants were identified. They included six singleton, coding variants that comprised five amino acid replacements and one silent site. Nucleotide diversity of the coding region (pi=0.0763+/-1.35 x 10(-4)) was 52 times lower than that of the noncoding regions (pi=3.93+/-5.26 x 10(-4)), indicative of significant sequence conservation. The occurrence of purifying selection was corroborated by phylogeny-based maximum likelihood analysis of the RB1 sequences of human and five primates, which yielded an estimated ratio of replacement to silent substitutions (omega) of 0.095 across all lineages. RB1 displayed extensive linkage disequilibrium over 174 kb, and only four unique recombination events, two in Africa and one each in Europe and Southwest Asia, were observed. Using a parsimony approach, 15 haplotypes could be inferred. Ten were found in Africa, though only 12.4% of the 274 chromosomes screened were of African origin. In non-Africans, a single haplotype accounted for from 63 to 84% of all chromosomes, most likely the consequence of natural selection and a significant bottleneck in effective population size during the colonization of the non-African continents.  相似文献   

8.
目的基于对突变问题的考虑和实验数据,提出达到科学鉴定结论的基本要求,供制定亲子鉴定标准参考。方法检测15个短串联重复序列基因座,包括CSF1 PO、FGA、TH01、TPOX、VWA、D3S1358、D5S818、D7S820、D8S1179、D13S317、D16S539、D18S51、D21S11等13个CODIS基因座以及PentaD和PentaE基因座,统计肯定父权的母亲、孩子、被告男子3人组合和排除父权的母亲、孩子、被告男子3人组合各100例。结果观察到排除父权的母亲、孩子、被告男子3人组合不符合遗传规律的短串联重复序列基因座数。获得了父权指数值的各种分布,包括模拟突变情况下每例父权指数的变化。结论为了避免潜在突变影响,任何情况下都不能仅根据一个遗传标记排除父权。累积非父排除概率和累计父权指数的阈值对于肯定父权和排除父权极为重要。系统的累积非父排除概率和累计父权指数达到一定阈值后,可以获得科学的鉴定结论。在不能达到阈值时,必须通过增加检测的遗传标记数量来达到要求。  相似文献   

9.
A double-blind histamine placebo controlled immunotherapy trial was performed to investigate the clinical effect of a purified and standardized Cladosporium herbarum allergen preparation. Thirty children with a clinical history suggesting mould-induced asthma and/or rhinoconjunctivitis were included. The diagnosis was confirmed by positive skin prick test and Phadebas RAST as well as positive bronchial and/or conjunctival provocation test to Cladosporium herbarum. Immunotherapy was given for 10 months in a double-blind manner to randomized groups with either Pharmalgen/Cladosporium herbarum preparation or histamine placebo. Allergic side effects to injections were common, especially during the peak of the mould season (July-September in Scandinavia). In the active group, 13/16 patients experienced general reactions during the first 10 months of treatment. After 6 months of treatment, eye, nose and bronchial symptom scores and peak expiratory flow rates were similar for the groups, maybe because most of the children were also sensitive to many other allergens, including Alternaria alternata. However, medication scores were significantly lower in the treated group (P less than 0.01). Bronchial (P less than 0.01) and conjunctival sensitivity (P = 0.01) were significantly reduced in the Cladosporium-treated group but not in the placebo group after 10 months of treatment. This is the first double-blind clinical trial showing the clinical efficacy of immunotherapy in children with mould-induced asthma.  相似文献   

10.
  总被引:1,自引:0,他引:1  
This paper applies a retrospective logistic regression model ( Prentice, 1976 ) using a sandwich variance estimator ( White, 1982 ; Zeger et al. 1985 ) to genetic association studies in which alleles are treated as dependent variables. The validity of switching the positions of allele and trait variables in the regression model is ensured by the invariance property of the odds ratio. The approach is shown to be able to accommodate many commonly seen designs, matched or unmatched alike, having either binary or quantitative traits. The resultant score statistic has potentially higher power than those that have previously appeared in the genetics literature. As a regression model in general, this approach may also be applied to incorporate covariates. Numerical examples implemented with standard software are presented.  相似文献   

11.
    
Background/aimC-reactive protein (CRP) to albumin ratio (CAR) is predictive marker of systemic inflammatory state in atherosclerotic coronary diseases when compared to predictive value of these two markers separately. We aimed to evaluate the relationship between CAR and the coronary artery calcium (CAC) score, Coronary Artery Disease-Reporting and Data System (CAD-RADS) score in patients’ unknown diagnosis of coronary artery disease (CAD) underwent coronary CTA (Computed Tomography Angiography) and were classified by CAD-RADS scores. Materials and methods A total of 187 patients consecutively referred for the evaluation of their chest pain underwent coronary CTA were included retrospectively. Results CRP, CAR, and CAD-RADS scores were higher in patients with CAC score > 400 than the other groups (p < 0.001). We found positive correlation between CAR and CAC score (r= 0.384, p < 0.001), and also there was a positive correlation between CAR and CAD-RADS score (r= 0.462, p < 0.001). Multivariate logistic regression analyses showed that low density lipoprotein cholesterol (LDL-C), CAD-RADS score, and CAR were independent predictors of CAC score (p < 0.05). Conclusion Higher CAR can be a predictive marker of atherosclerosis and CAD. CAR may be useful in the management of patients before invasive coronary angiography. Further studies are needed to clarify the pathophysiologic role of CAR in patients with atherosclerotic coronary heart diease.  相似文献   

12.
Renal fine-needle aspiration biopsy (FNAB) is used in several clinical scenarios: in patients with classic radiographic lesions; in non-operable patients with presumed high stage disease; and in patients with radiographic problematic lesions. Although overall, FNAB is a sensitive test, its role in the latter two populations has not been clearly established. To investigate the utility of FNAB in these patients, we retrospectively evaluated 43 renal FNABs in regards to diagnostic accuracy and clinical outcome. FNAB diagnoses were: malignant (36), suspicious (6), and insufficient (1). Our results indicate: 1) renal FNAB is accurate in patients with high stage lesions; 2) FNAB is less accurate in patients with radiographic problematic lesions; 3) the FNAB diagnosis of malignant increases the post-FNAB probability of malignancy, whereas the diagnosis of suspicious decreases the probability; and 4) there is excellent correlation for nuclear grade. We conclude that renal FNAB is useful in evaluating renal masses. Diagn Cytopathol 1996;14:14–19. © 1996 Wiley-Liss, Inc.  相似文献   

13.

Context:

Type I superior labrum anterior-posterior (SLAP) lesions involve degenerative fraying and probably are not the cause of shoulder pain. Type II to IV SLAP lesions are tears of the labrum.

Objective:

To determine the diagnostic accuracy of patient history and the active compression, anterior slide, and crank tests for type I and type II to IV SLAP lesions.

Design:

Cohort study.

Setting:

Clinic.

Patients or Other Participants:

Fifty-five patients (47 men, 8 women; age = 40.6 ± 15.1 years) presenting with shoulder pain.

Intervention(s):

For each patient, an orthopaedic surgeon conducted a clinical examination of history of trauma; sudden onset of symptoms; history of popping, clicking, or catching; age; and active compression, crank, and anterior slide tests. The reference standard was the intraoperative diagnosis. The operating surgeon was blinded to the results of the clinical examination.

Main Outcome Measure(s):

Diagnostic utility was calculated using the receiver operating characteristic curve and area under the curve (AUC), sensitivity, specificity, positive likelihood ratio (+LR), and negative likelihood ratio (−LR). Forward stepwise binary regression was used to determine a combination of tests for diagnosis.

Results:

No history item or physical examination test had diagnostic accuracy for type I SLAP lesions (n = 13). The anterior slide test had utility (AUC = 0.70, +LR = 2.25, −LR = 0.44) to confirm and exclude type II to IV SLAP lesions (n = 10). The combination of a history of popping, clicking, or catching and the anterior slide test demonstrated diagnostic utility for confirming type II to IV SLAP lesions (+LR = 6.00).

Conclusions:

The anterior slide test had limited diagnostic utility for confirming and excluding type II to IV SLAP lesions; diagnostic values indicated only small shifts in probability. However, the combination of the anterior slide test with a history of popping, clicking, or catching had moderate diagnostic utility for confirming type II to IV SLAP lesions. No single item or combination of history items and physical examination tests had diagnostic utility for type I SLAP lesions.  相似文献   

14.
目的 探讨外周血单核细胞/淋巴细胞比值(MLR)对冠心病的诊断价值。方法 回顾分析2018年3月~2019年5月我院302例接受冠状动脉造影(CAG)检查患者的临床资料,根据CAG结果分为冠心病组(220例)和非冠心病组(82例),收集患者的一般资料及临床实验室结果,根据血常规计算MLR,通过Gensini法对冠脉狭窄程度进行评估,分析MLR与冠心病狭窄程度相关性,绘制ROC曲线评估MLR预测冠心病诊断价值。结果 冠心病组中男性、高血压病史所占比及单核细胞计数、淋巴细胞计数、MLR高于非冠心病组,差异有统计学意义(P<0.05);多因素Logistic回归分析显示,MLR是冠心病的独立危险因素[OR=3.94,95%CI(1.200~12.950),P=0.002];Spearman相关性分析显示,Gensini评分与MLR水平呈正相关(r=0.437,P<0.05);ROC曲线分析显示,MLR值为0.18时,MLR预测冠心病的敏感性为69.03%,特异度为64.81%[AUC=0.727,95%CI(0.683~0.771),P=0.005]。结论 MLR是冠心病发生的独立危险因素,且与冠心病狭窄程度呈正相关,对诊断冠心病有一定的诊断价值。  相似文献   

15.
    
Diffusion kurtosis imaging (DKI) can offer a useful complementary tool to routine diffusion MRI for improved stratification of heterogeneous tissue damage in acute ischemic stroke. However, its relatively long imaging time has hampered its clinical application in the emergency setting. A recently proposed fast DKI approach substantially shortens the imaging time, which may help to overcome the scan time limitation. However, to date, the sensitivity of the fast DKI protocol for the imaging of acute stroke has not been fully described. In this study, we performed routine and fast DKI scans in a rodent model of acute stroke, and compared the sensitivity of diffusivity and kurtosis indices (i.e. axial, radial and mean) in depicting acute ischemic lesions. In addition, we analyzed the contrast‐to‐noise ratio (CNR) between the ipsilateral ischemic and contralateral normal regions using both conventional and fast DKI methods. We found that the mean kurtosis shows a relative change of 47.1 ± 7.3% between the ischemic and contralateral normal regions, being the most sensitive parameter in revealing acute ischemic injury. The two DKI methods yielded highly correlated diffusivity and kurtosis measures and lesion volumes (R2 ? 0.90, p < 0.01). Importantly, the fast DKI method exhibited significantly higher CNR of mean kurtosis (1.6 ± 0.2) compared with the routine tensor protocol (1.3 ± 0.2, p < 0.05), with its CNR per unit time (CNR efficiency) approximately doubled when the scan time was taken into account. In conclusion, the fast DKI method provides excellent sensitivity and efficiency to image acute ischemic tissue damage, which is essential for image‐guided and individualized stroke treatment. Copyright © 2016 John Wiley & Sons, Ltd.  相似文献   

16.
We have been working on identifying sources of variability in data from transgenic mouse mutation assays in order to develop appropriate statistical methods and designs for routine studies. Data from our lab and elsewhere point to the presence of significant animal-to-animal variability, which must be taken into account in statistical hypothesis tests. Here, the usual Cochran-Armitage (CA) test for trend in mutant frequencies, which takes the transgene as the experimental unit, and a generalized Cochran-Armitage test (GCA), which takes the animal as the experimental unit, are contrasted in computer simulations that help to quantify the differences between these statistical tests. The simulations report the statistical power of each test to detect treatment group differences, and their type I error rates. We find in general that the GCA test performs poorly compared to the CA test when it is appropriate to take the transgene as the experimental unit, and the study also uses a small number of animals. However, the CA test performs poorly in small group-size studies when the animal is the appropriate experimental unit. Extensions of the computer simulations allow for identification of cost-effective experimental designs. The results emphasize that the benefits of using additional animals in these mutation studies can be realized without substantial increases in costs. Here we illustrate the methods for liver studies in our lab. These methods can be used to derive optimal experimental designs for any combination of spontaneous mutant frequency and animal-to-animal variability. © 1995 Wiley-Liss, Inc.  相似文献   

17.
A method of estimating the likelihood ratio and the risk of an individual being affected with Martin Bell syndrome (MBS) from anthropometric measurements is described. The procedure is based on the discriminant functions (one for each sex), generated in our previous study in order to separate the individuals with MBS from the normal individuals. The procedure is illustrated by the examples of estimating the likelihood and the likelihood ratio in four individuals of either sex, belonging to MBS families, where the discriminant score value obtained from each individual is compared with the empirical (normalized) distribution of discriminant scores from the known MBS and normal subjects of a corresponding sex. The ways in which the risk of an individual being MBS is estimated in the general population or in members of the MBS families are indicated. The limitations of the discriminant diagnosis based on body measurements, as well as its particular applications in studies of the Martin-Bell syndrome, are discussed.  相似文献   

18.
    
Association studies, based on either population data or familial data, have been widely applied to mapping of genes underlying complex diseases. In family-based association studies, using case-parent triad families, the popularly used transmission/disequilibrium test (TDT) was proposed for avoidance of spurious association results caused by other confounders such as population stratification. Originally, the TDT was developed for analysis of binary disease data. Extending it to allow for quantitative trait analysis of complex diseases and for robust analysis of binary diseases against the uncertainty of mode of inheritance has been thoroughly discussed. Nevertheless, studies on robust analysis of quantitative traits for complex diseases received relatively less attention. In this paper, we use parent-offspring triad families to demonstrate the feasibility of establishment of the robust candidate-gene association tests for quantitative traits. We first introduce the score statistics from the conditional likelihoods based on parent-offspring triad data under various genetic models. By applying two existing robust procedures we then construct the robust association tests for analysis of quantitative traits. Simulations are conducted to evaluate empirical type I error rates and powers of the proposed robust tests. The results show that these robust association tests do exhibit robustness against the effect of misspecification of the underlying genetic model on testing powers.  相似文献   

19.
BACKGROUND: There is still a lack of standardization of the atopy patch test (APT) in test procedures and evaluation methods. Our aim was to examine the reproducibility of APT results and to compare visual evaluation to chromametry and laser Doppler imaging. METHODS: Fifty-two volunteers with atopic eczema/dermatitis syndrome (AEDS) were included. The APT was performed on tape-stripped and unstripped test fields on their backs using cat dander, house dust mite and grass pollen allergens from two different suppliers. Responders were re-tested 4-12 weeks later with the same allergens on their forearms. RESULTS: Using Allergopharma allergens, 14 (26.9%) volunteers showed one or more positive reactions. The reproducibility rate was 56.3%. The Erlangen atopy score in APT-positive and negative volunteers was 19 +/- 6 vs 15 +/- 6. The test agreement in volunteers tested with both allergens, from Allergopharma and Stallergènes, was poor. Correlation of the results between the three evaluation methods was significant (P < or = 0.001). CONCLUSIONS: The low reproducibility rate of APT results and the poor inter-test-agreement using allergens from different suppliers show that much work remains to make the APT a reliable tool in identifying relevant aeroallergens that lead to flare ups of AEDS. Compared to chromametry and laser Doppler imaging, visual scoring was superior in differentiation between irritative and allergic reactions.  相似文献   

20.
Basner M  Griefahn B  Müller U  Plath G  Samel A 《Sleep》2007,30(10):1349-1361
OBJECTIVES: EEG arousals are associated with autonomic activations. Visual EEG arousal scoring is time consuming and suffers from low interobserver agreement. We hypothesized that information on changes in heart rate alone suffice to predict the occurrence of cortical arousal. METHODS: Two visual AASM EEG arousal scorings of 56 healthy subject nights (mean age 37.0 +/- 12.8 years, 26 male) were obtained. For each of 5 heartbeats following the onset of 3581 consensus EEG arousals and of an equal number of control conditions, differences to a moving median were calculated and used to estimate likelihood ratios (LRs) for 10 categories of heartbeat differences. Comparable to 5 consecutive diagnostic tests, these LRs were used to calculate the probability of heart rate responses being associated with cortical arousals. RESULTS: EEG and ECG arousal indexes agreed well across a wide range of decision thresholds, resulting in a receiver operating characteristic (ROC) with an area under the curve of 0.91. For the decision threshold chosen for the final analyses, a sensitivity of 68.1% and a specificity of 95.2% were obtained. ECG and EEG arousal indexes were poorly correlated (r = 0.19, P <0.001, ICC = 0.186), which could in part be attributed to 3 outliers. The Bland-Altman plot showed an unbiased estimation of EEG arousal indexes by ECG arousal indexes with a standard deviation of +/- 7.9 arousals per hour sleep. In about two-thirds of all cases, ECG arousal scoring was matched by at least one (22.2%) or by both (42.5%) of the visual scorings. Sensitivity of the algorithm increased with increasing duration of EEG arousals. The ECG algorithm was also successfully validated with 30 different nights of 10 subjects (mean age 35.3 [ 13.6 years, 5 male). CONCLUSIONS: In its current version, the ECG algorithm cannot replace visual EEG arousal scoring. Sensitivity for detecting <10-s EEG arousals needs to be improved. However, in a nonclinical population, it may be valuable to supplement visual EEG arousal scoring by this automatic, objective, reproducible, cheap, and time-saving method.  相似文献   

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