{"component": "clause", "props": {"groups": [{"snippet_links": [{"key": "the-database", "type": "definition", "offset": [3, 15]}, {"key": "organ-system", "type": "definition", "offset": [92, 104]}, {"key": "specific-categories", "type": "clause", "offset": [110, 129]}, {"key": "categories-of", "type": "clause", "offset": [287, 300]}, {"key": "logistic-regression", "type": "clause", "offset": [327, 346]}, {"key": "relationship-between", "type": "clause", "offset": [377, 397]}, {"key": "the-total", "type": "clause", "offset": [497, 506]}, {"key": "ratio-test", "type": "definition", "offset": [695, 705]}, {"key": "the-individual", "type": "clause", "offset": [853, 867]}, {"key": "ethnic-groups", "type": "definition", "offset": [994, 1007]}, {"key": "reference-group", "type": "definition", "offset": [1037, 1052]}, {"key": "related-to", "type": "definition", "offset": [1091, 1101]}, {"key": "number-of", "type": "clause", "offset": [1399, 1408]}, {"key": "cleft-palate", "type": "definition", "offset": [1835, 1847]}, {"key": "resulting-from", "type": "definition", "offset": [2247, 2261]}, {"key": "depending-on-the", "type": "clause", "offset": [2385, 2401]}, {"key": "for-example", "type": "clause", "offset": [2429, 2440]}, {"key": "to-determine", "type": "clause", "offset": [2442, 2454]}, {"key": "significant-relationship", "type": "definition", "offset": [2625, 2649]}, {"key": "this-article", "type": "definition", "offset": [3129, 3141]}, {"key": "statistical-analyses", "type": "clause", "offset": [3481, 3501]}], "snippet": "In the database congenital malformations are classified through a standard coding system by organ system into specific categories or into non-specific categories if no details are known. Eight different organ systems are distinguished for which there are 51 specified and 20 unspecified categories of congenital malformations. Logistic regression models were used to study the relationship between maternal ethnicity and congenital malformations. The overall relationship between ethnic group and the total prevalence of congenital malformations, the total prevalence within the eight organ systems and the prevalence of some specific congenital malformations was determined with the Likelihood Ratio Test (LRT). If this test was significant it showed the existence of an overall relationship between ethnicity and congenital malformations. Thereafter, the individual significance of the calculated odds ratios (ORs) expressing the observed risk differences in prevalence between the different ethnic groups and the Dutch group, used as reference group, was studied. Because maternal age is related to the ethnic group and to the occurrence of certain congenital malformations, we calculated the ORs both unadjusted and adjusted for the age of the mother. Because the prevalence of some malformations was low, even in this 5-year birth cohort, not all could be tested. We decided that the predicted number of malformations had to be at least 5 in each ethnic group to perform a worthwhile and clinically significant test. Therefore, from the 51 specific malformations registered in the linked national database only the following 15 were analysed for possible differences between ethnic groups: neural tube defects (NTD); congenital malformations of the ears; ventricular septal defect; single umbilical artery; cleft lip with/without cleft palate; cleft palate without cleft lip; intestinal/anorectal atresia; hypospadias and/or epispadias; undescended testes; polydactyly; syndactyly; deformities of the foot without NTD; Down\u2019s syndrome; other chromosomal malformations; and multiple malformations. Many comparisons were performed to test for a possible ethnic difference in prevalence of any congenital malformations. To avoid chance findings resulting from to multiple testing we applied a Bonferroni correction in which the usual critical value of 0.05 is adapted to a lower one depending on the number of tests performed. For example, to determine in which of the ethnic groups a possible difference in overall prevalence of malformations exists, the critical value used was 0.05/6=0.008. To test whether there is any significant relationship between ethnicity and one of the eight organ systems the critical value used for the LRT\u2019s was 0.05/8=0.006. Significant organ systems were selected for further examination to determine which ethnic group differed significantly from the Dutch reference group using a critical value of 0.05/8*6=0.001. For the analyses of the specific malformations similar adaptations of the critical value were performed depending on the number of malformations tested within each organ system. This article will only focus on the significant observations where the calculated P-values are below the Bonferroni corrected critical values. The Bonferroni correction is conservative. Therefore, the overall risk of stating a possible relationship of any malformation with ethnicity, while in reality it does not exist, is kept at least below 5%. All statistical analyses were performed in SPSS, version 11.", "size": 2, "samples": [{"hash": "fIuS0SXWv8Y", "uri": "/contracts/fIuS0SXWv8Y#statistical-methods", "label": "Doctoral Thesis", "score": 19.0, "published": true}, {"hash": "cQ9qEESIt7F", "uri": "/contracts/cQ9qEESIt7F#statistical-methods", "label": "Doctoral Thesis", "score": 19.0, "published": true}], "hash": "fdd5dfae8784e7935809db759291ee34", "id": 1}, {"snippet_links": [{"key": "the-model", "type": "clause", "offset": [151, 160]}, {"key": "according-to", "type": "definition", "offset": [959, 971]}, {"key": "copies-of", "type": "definition", "offset": [986, 995]}, {"key": "effect-of-the", "type": "clause", "offset": [1384, 1397]}, {"key": "frequency-of", "type": "clause", "offset": [1470, 1482]}], "snippet": "Two statistical methods were used to perform the GWAS, namely weighted single-step GBLUP (WssGBLUP; \u2587\u2587\u2587\u2587 et al. 2012) and \u2587\u2587\u2587\u2587\u2587\u2587 (\u2587\u2587\u2587\u2587\u2587\u2587 et al. 2011). The model adopted for WssGBLUP was: y=1\u00b5+Zaa+e, where y is the vector of phenotypes, \u00b5 is the overall mean, a is the vector of additive genetic effects, 1 is a vector of ones, Za is an incidence matrix relating the phenotypes to a, and e is the vector of residuals. The covariance between a and e was assumed to be zero and their variances were considered to be H\u03c3 2 and I\u03c3 2, respectively, where \u03c3 2 and \u03c3 2 are the direct additive and residual variance, respectively, H is the matrix which combines pedigree and genomic information (\u2587\u2587\u2587\u2587\u2587\u2587\u2587 et al. 2010), and I is an identity matrix. The SNP effects (\u00fb) were calculated as in Stranden & \u2587\u2587\u2587\u2587\u2587\u2587\u2587 (2009): \u00fb=DP\u2019[PDP\u2019]-1ag, where D is a diagonal matrix that contains the weights for the SNPs, P is a matrix relating genotypes of each locus (coded as 0, 1 or 2 according to the number of copies of allele B) and ag is a vector with the estimated breeding values of genotyped animals. D, \u00e2 and \u00fb were iteratively recomputed over three iterations. In the first iteration (w1), the diagonal elements of D (di) were assumed to be 1 (i.e., the same weight for all markers). For the subsequent iterations (w2 and w3), di was calculated as: di=\u00fbi2pi(1-pi), where \u00fbi is the allele substitution effect of the ith marker, estimated from the previous iteration, and pi is the allele frequency of the second allele of the ith marker. The WssGBLUP was adopted using two sets of data, one considering all available phenotypic information (SI; n=45,000) and another considering phenotypes just from genotyped animals (SII; n=2,000). The three different weights for the SNPs (w1 to w3) and the two sets of data (SI and SII) resulted in six different solutions for the SNP effects obtained under the WssGBLUP method. BayesC was applied under the model:", "size": 2, "samples": [{"hash": "78JxEtUNzyu", "uri": "/contracts/78JxEtUNzyu#statistical-methods", "label": "Research Agreement", "score": 25.8435745239, "published": true}, {"hash": "3Y3zScrIzN2", "uri": "/contracts/3Y3zScrIzN2#statistical-methods", "label": "Research Agreement", "score": 23.9493160248, "published": true}], "hash": "610fe8b69d6946e88c194c8027470139", "id": 2}, {"snippet_links": [{"key": "the-participants", "type": "definition", "offset": [340, 356]}, {"key": "in-the-study", "type": "clause", "offset": [370, 382]}, {"key": "effectiveness-of-the", "type": "clause", "offset": [496, 516]}, {"key": "logistic-regression", "type": "clause", "offset": [535, 554]}, {"key": "independent-variable", "type": "clause", "offset": [708, 728]}, {"key": "intervention-conditions", "type": "clause", "offset": [758, 781]}, {"key": "gender-and", "type": "clause", "offset": [805, 815]}], "snippet": "A randomization analysis was conducted to check the comparability of the different conditions at baseline. This was done by chi-square statistics for categorical and dichotomous variables, while t-tests were used for continuous variables. An attrition analysis was conducted to see whether there were differences in baseline scores between the participants who remained in the study and those who withdrew at post-test. This was done by analyses of variance and chi-square. Finally, to check the effectiveness of the tailored letters, logistic regression analyses were conducted with benzodiazepine cessation at post-test as the dependent variable (\u20180\u2019- did not quit and \u20181\u2019 \u2013 did quit) and condition as the independent variable. All comparisons between the intervention conditions were adjusted for age, gender and benzodiazepine dose (in diazepam equivalents).", "size": 2, "samples": [{"hash": "jKJRneTIcQR", "uri": "/contracts/jKJRneTIcQR#statistical-methods", "label": "Not Applicable", "score": 18.0, "published": true}, {"hash": "jC9rICfqq6H", "uri": "/contracts/jC9rICfqq6H#statistical-methods", "label": "Not Applicable", "score": 18.0, "published": true}], "hash": "35edf91c57243c05d79e970d3dafa62b", "id": 3}, {"snippet_links": [], "snippet": "12.1.1 Comparisons of Interest [***]", "size": 2, "samples": [{"hash": "bdPnvKmidhJ", "uri": "/contracts/bdPnvKmidhJ#statistical-methods", "label": "Service Agreement (Vascular Biogenics Ltd.)", "score": 21.5420951843, "published": true}], "hash": "5eceea5ff199d766c8e47b6875dcb3c2", "id": 4}, {"snippet_links": [{"key": "test-material", "type": "definition", "offset": [59, 72]}, {"key": "weight-loss", "type": "clause", "offset": [284, 295]}, {"key": "primary-endpoints", "type": "clause", "offset": [564, 581]}, {"key": "completion-of-the-study", "type": "clause", "offset": [1013, 1036]}, {"key": "protocol-approval", "type": "clause", "offset": [1052, 1069]}, {"key": "investigator-signature", "type": "definition", "offset": [1082, 1104]}, {"key": "protocol-synopsis", "type": "clause", "offset": [1107, 1124]}], "snippet": "All subjects who are randomized, take one or more doses of test material and have at least one post treatment efficacy measurement will be included in the analysis. Comparisons between treatments will be assessed using an *** with factors of ***, *** and *** and with *** for percent weight loss, and *** for percentage of subjects with at least 5% weight loss. A step-down multiple comparison procedure will be used to compare each dose group with ***. That is, comparison with *** will start at the ***. If the statistical test is significant at *** for both co-primary endpoints, then the test will proceed to the *** also at the ***. If the statistical comparison is not significant at the ***, then the statistical test will be stopped and the *** will not be tested. If both dose groups are significantly better than ***, then the two active dose groups will be compared. A *** of difference in response rate between treatment groups will be derived. The *** for subjects who discontinue treatment prior to completion of the study, ***. INTERNAL PROTOCOL APPROVAL 2 PRINCIPAL INVESTIGATOR SIGNATURE 3 PROTOCOL SYNOPSIS 4", "size": 2, "samples": [{"hash": "gWR6eqkVEur", "uri": "/contracts/gWR6eqkVEur#statistical-methods", "label": "Master Services Agreement (Vivus Inc)", "score": 24.3483905792, "published": true}], "hash": "b2e5e86fda841e421c6dc46d874df2c4", "id": 5}, {"snippet_links": [{"key": "the-primary", "type": "clause", "offset": [17, 28]}, {"key": "based-on", "type": "definition", "offset": [46, 54]}, {"key": "week-1", "type": "definition", "offset": [157, 163]}, {"key": "daily-average", "type": "definition", "offset": [328, 341]}, {"key": "baseline-average", "type": "definition", "offset": [408, 424]}, {"key": "prior-to", "type": "clause", "offset": [516, 524]}, {"key": "the-model", "type": "clause", "offset": [585, 594]}, {"key": "baseline-value", "type": "definition", "offset": [596, 610]}, {"key": "treatment-group", "type": "definition", "offset": [637, 652]}, {"key": "concomitant-medication", "type": "clause", "offset": [661, 683]}, {"key": "group-by", "type": "clause", "offset": [726, 734]}, {"key": "additional-structures", "type": "clause", "offset": [918, 939]}, {"key": "protocol-and-statistical-analysis-plan", "type": "clause", "offset": [978, 1016]}], "snippet": "Primary Analysis The primary analysis will be based on a mixed model repeated measures (MMRM) analysis to estimate the difference in change from baseline to Week 12 in mean average pain score in patients receiving ricolinostat versus those receiving placebo. The outcome will include the weekly mean change from baseline in the daily average pain scores computed each week during Week 1 through Week 12. The baseline average pain score will be computed as the mean of the average daily pain scores during the 7 days prior to randomization. The following covariates will be included in the model: baseline value of the pain score, visit, treatment group, use of concomitant medication for painful DPN (yes vs. no), a treatment group by visit interaction term, and a baseline pain score by visit interaction term. The model will first be fit with an unstructured covariance matrix. If this model does not converge, then additional structures will be considered as outlined in the protocol and Statistical Analysis Plan (SAP).", "size": 1, "samples": [{"hash": "80TLt0wRwY9", "uri": "/contracts/80TLt0wRwY9#statistical-methods", "label": "Investigator Agreement", "score": 29.8500652313, "published": true}], "hash": "bad43dfedd54f8ad69d30f7e6d3bb015", "id": 6}, {"snippet_links": [{"key": "title-x", "type": "definition", "offset": [34, 41]}, {"key": "family-planning-clinic", "type": "definition", "offset": [58, 80]}, {"key": "in-georgia", "type": "clause", "offset": [87, 97]}, {"key": "year-2006", "type": "clause", "offset": [106, 115]}, {"key": "data-files", "type": "clause", "offset": [207, 217]}, {"key": "zip-code", "type": "definition", "offset": [239, 247]}, {"key": "with-regard-to", "type": "clause", "offset": [259, 273]}, {"key": "federal-poverty-line", "type": "definition", "offset": [353, 373]}, {"key": "at-risk", "type": "definition", "offset": [536, 543]}, {"key": "unintended-pregnancy", "type": "clause", "offset": [548, 568]}, {"key": "census-tract", "type": "definition", "offset": [577, 589]}, {"key": "risk-in", "type": "clause", "offset": [669, 676]}, {"key": "calculate-the", "type": "clause", "offset": [754, 767]}, {"key": "pregnancy-terminations", "type": "clause", "offset": [775, 797]}, {"key": "the-state", "type": "clause", "offset": [820, 829]}, {"key": "total-number-of", "type": "definition", "offset": [914, 929]}, {"key": "reproductive-age", "type": "definition", "offset": [987, 1003]}, {"key": "geographic-area", "type": "clause", "offset": [1066, 1081]}, {"key": "associated-with", "type": "definition", "offset": [1184, 1199]}, {"key": "age-category", "type": "definition", "offset": [1261, 1273]}, {"key": "based-on", "type": "definition", "offset": [1745, 1753]}, {"key": "distribution-of", "type": "clause", "offset": [1767, 1782]}, {"key": "sum-of", "type": "clause", "offset": [1832, 1838]}, {"key": "statistical-analysis", "type": "clause", "offset": [1887, 1907]}, {"key": "to-account", "type": "definition", "offset": [2065, 2075]}, {"key": "the-study", "type": "definition", "offset": [2129, 2138]}, {"key": "approved-by", "type": "clause", "offset": [2143, 2154]}, {"key": "institutional-review-board", "type": "definition", "offset": [2176, 2202]}], "snippet": "The physical addresses of all 242 Title X publicly-funded family planning clinic sites in Georgia for the year 2006 were geocoded using ArcGis (ArcMapVersion 10). Next, we used the American Community Survey data files to characterize each zip code in Georgia with regard to key population-level characteristics (e.g., proportion of households below the federal poverty line, and with characteristics such as race/ethnicity and age). The NSFG race- and age-specific estimates were used to estimate the proportion of the base population \u201cat risk\u201d of unintended pregnancy in each census tract and HUD tract-zip code crosswalk file were used to aggregate the population at risk in each zip code area. We then utilized Georgia\u2019s pregnancy termination file to calculate the number pregnancy terminations occurring for each of the state\u2019s zip codes for 2006. For each ZCTA, an abortion rate was calculated based upon the total number of terminated pregnancies over the total number of women of reproductive age (15-44 years) at risk of unintended pregnancy residing in the geographic area. The covariates were variables that were both included in our dataset and in past studies shown to be associated with unintended pregnancies. These variables included the woman\u2019s age category (15-17, 18-19, 20-24, 25-29, 30- 34, and 35-44), ethnicity and race (non-Hispanic White, non-Hispanic Black, Hispanic, and other), percentage poverty per zip code (0-10%, 10-20%, 20-30%, and 30+%), geographical characteristic (metropolitan/urban, micropolitan/large rural, and small/isolated rural town), and distance in meters away from the closest Title X family planning clinic (0-4000, 4000-7000, 7000-11000, 11000-15000, and 15000+ meters). Distance categories were based on the quintile distribution of abortion rates occurring from the ITOP file. The sum of all abortions per variable was calculated using Statistical Analysis System (SAS Institute, Inc., Cary, NC). The abortion rate per variable was analyzed using a Poisson model (SAS Proc Genmod) utilizing robust standard errors to account for multiple observations within each zip code area. The study was approved by the Emory University Institutional Review Board [8].", "size": 1, "samples": [{"hash": "2AGT6WYHhtb", "uri": "/contracts/2AGT6WYHhtb#statistical-methods", "label": "Distribution Agreement", "score": 20.9134197235, "published": true}], "hash": "1807a12b91ad2754dfd4be8d0c27580c", "id": 7}, {"snippet_links": [{"key": "chapter-4", "type": "definition", "offset": [158, 167]}, {"key": "effect-of", "type": "clause", "offset": [174, 183]}, {"key": "immune-response", "type": "definition", "offset": [202, 217]}, {"key": "ratio-test", "type": "definition", "offset": [455, 465]}, {"key": "all-parameters", "type": "definition", "offset": [505, 519]}, {"key": "standard-deviation", "type": "definition", "offset": [571, 589]}, {"key": "the-\u2587", "type": "clause", "offset": [644, 649]}, {"key": "the-student", "type": "clause", "offset": [680, 691]}, {"key": "relationship-between", "type": "clause", "offset": [754, 774]}, {"key": "age-and-sex", "type": "clause", "offset": [963, 974]}, {"key": "associated-with", "type": "definition", "offset": [1030, 1045]}, {"key": "not-included", "type": "clause", "offset": [1092, 1104]}, {"key": "final-analysis", "type": "definition", "offset": [1112, 1126]}, {"key": "the-model", "type": "clause", "offset": [1281, 1290]}, {"key": "and-diversity", "type": "clause", "offset": [1535, 1548]}, {"key": "the-p", "type": "clause", "offset": [1813, 1818]}, {"key": "to-allow-the", "type": "clause", "offset": [1957, 1969]}, {"key": "effect-on-the", "type": "clause", "offset": [1998, 2011]}, {"key": "sample-size", "type": "definition", "offset": [2139, 2150]}, {"key": "based-on", "type": "definition", "offset": [2184, 2192]}, {"key": "the-association", "type": "clause", "offset": [2593, 2608]}, {"key": "statistical-analyses", "type": "clause", "offset": [3236, 3256]}, {"key": "core-team", "type": "definition", "offset": [3280, 3289]}], "snippet": "The microbiome composition for each group of the different demographical ar- eas was assumed to follow a Dirichlet \u2013 multinomial distribution with 6 cate- 74 Chapter 4 \u2013 The effect of gut-microbiome on immune response gories which represents the 6 most abundant phyla (Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, unclassified bacteria and pooled). The difference in the microbiome composition between groups was tested using the likelihood ratio test statistic with 6 degrees of freedom. \u02d8 All parameters of interest were described as means or frequency ( standard deviation). Prevalence rates were calculated and compared using the \u2587\u2587\u2587\u2587\u2587\u2587\u2587 \u2587\u2587\u2587- square test, while the Student t-test was used to compare continuous variables. To study the relationship between cytokines and microbiome over the two time points, a linear mixed effect regression model was fitted with helminth sta- tus and treatment as covariates. All models have been adjusted with age and sex, however, since both covariates were not significantly associated with the cytokine responses in any model, they are not included in the final analysis. The correla- tion between observations from the same subjects was modelled by including a subject-specific random effect. The microbiome was included in the model ei- ther as a bacterial proportion or by the \u2587\u2587\u2587\u2587\u2587\u2587\u2587 diversity index. The cytokine responses were log10-transformed (log10(concentration + 1)) to obtain normally distributed variables. First, we analyzed the main effect of bacterial proportion and diversity on cytokine responses. Second, to allow for different effect sizes of bacterial proportion or diversity on cytokine responses in helminth-positive versus -negative subjects, an interaction term between bacterial categories and infection was included in the model. The p-value for this interaction term in- dicated the statistical evidence for different effect sizes in helminth-positive or \u2013negative groups. To allow the estimation of the treatment effect on the relationship between bacterial proportion and cytokine responses, the randomized controlled trial de- sign was used. Since the sample size is too small, we only stratified based on randomization arm. Hence, the effect of treatment cannot be distinguished from the effect of helminth infection. Therefore, we explored the relationship between cytokines and microbiome after anthelminthic treatment. A linear mixed effect model was fitted with bacterial proportion or diversity, and treatment as covari- ates. This model was able to characterize three different associations, namely the association between bacterial proportion or diversity on cytokines at pre- treatment, the difference of the association at pre-treatment and at post-treatment in the placebo group (time effect), as well as the difference of the association at post-treatment between albendazole and placebo group. For each outcome separately, these models were fitted on subjects who at least had an observation at pre-treatment. The lme4 package in statistical software R was used for model fitting. The significance of the covariate effect was obtained from the likelihood ratio test. Bonferroni correction was used to adjust for mul- tiple testing. The statistical analyses were performed in R [R Core Team (R Core Team)] with mainly lme4 and lmerTest packages [\u2587\u2587\u2587\u2587\u2587 et al. (2015), \u2587\u2587\u2587\u2587\u2587\u2587\u2587\u2587\u2587\u2587 et al. (2017)]. The full record was created using the knitr package in R [Xie (2018)]", "size": 1, "samples": [{"hash": "gx69tgKVFp6", "uri": "/contracts/gx69tgKVFp6#statistical-methods", "label": "Doctoral Thesis", "score": 28.515291214, "published": true}], "hash": "859273951c8bc93eb09d1d50d98fb8f6", "id": 8}, {"snippet_links": [{"key": "the-objective", "type": "clause", "offset": [0, 13]}, {"key": "phase-ii-study", "type": "clause", "offset": [22, 36]}, {"key": "the-safety", "type": "clause", "offset": [52, 62]}, {"key": "administration-of", "type": "clause", "offset": [69, 86]}, {"key": "equal-to", "type": "definition", "offset": [172, 180]}, {"key": "frequency-of", "type": "clause", "offset": [417, 429]}, {"key": "surface-area", "type": "definition", "offset": [559, 571]}, {"key": "time-to-complete", "type": "clause", "offset": [573, 589]}], "snippet": "The objective of this Phase II study is to evaluate the safety of IM administration of VM202 in subjects with moderate or high-risk CLI (\u2587\u2587\u2587\u2587\u2587\u2587\u2587\u2587\u2587\u2587 Clinical Severity Score equal to 4 or 5) who are poor or non- candidates for surgical or percutaneous revascularization; and, to evaluate potential bioactivity of IM administration of VM202 in subjects with CLI, when compared with placebo, on rest pain (as assessed by frequency of rest pain, pain medication use history, sleeping history, and intensity of rest pain) or leg ulcer healing (as assessed by ulcer surface area, time to complete healing), perfusion (MRA), hemodynamic assessment (ABI & TBI), tissue oxygenation (TcPO2) and the incidence and extent of lower leg amputation or other surgical interventions.", "size": 1, "samples": [{"hash": "flq5JWBVZnY", "uri": "/contracts/flq5JWBVZnY#statistical-methods", "label": "Investigator's Agreement", "score": 34.605594635, "published": true}], "hash": "c5dbf60c37da8fd831675664203209a6", "id": 9}, {"snippet_links": [{"key": "distributions-of", "type": "clause", "offset": [73, 89]}, {"key": "random-sample", "type": "clause", "offset": [125, 138]}, {"key": "the-guidelines", "type": "clause", "offset": [410, 424]}, {"key": "of-agreement", "type": "clause", "offset": [476, 488]}, {"key": "to-account", "type": "definition", "offset": [831, 841]}, {"key": "provide-a", "type": "definition", "offset": [883, 892]}, {"key": "missing-data", "type": "definition", "offset": [916, 928]}, {"key": "the-participants", "type": "definition", "offset": [1156, 1172]}, {"key": "having-a", "type": "definition", "offset": [1191, 1199]}, {"key": "page-4", "type": "clause", "offset": [1223, 1229]}, {"key": "in-the-united-states", "type": "clause", "offset": [1520, 1540]}, {"key": "computed-tomography", "type": "definition", "offset": [1594, 1613]}, {"key": "table-1", "type": "clause", "offset": [2272, 2279]}, {"key": "the-majority", "type": "clause", "offset": [2281, 2293]}, {"key": "myocardial-infarction", "type": "clause", "offset": [2526, 2547]}, {"key": "distribution-of", "type": "clause", "offset": [2727, 2742]}, {"key": "based-on", "type": "definition", "offset": [2759, 2767]}, {"key": "the-original", "type": "definition", "offset": [2768, 2780]}, {"key": "other-cause", "type": "clause", "offset": [2902, 2913]}, {"key": "table-2", "type": "definition", "offset": [3127, 3134]}, {"key": "table-3", "type": "clause", "offset": [3173, 3180]}, {"key": "complete-sets", "type": "clause", "offset": [3535, 3548]}], "snippet": "NIH-PA Author Manuscript \u03c72 tests were used to assess differences in the distributions of categorical phenotypes between the random sample of sibling used in this study and the cohort of concordant siblings from which the random sample was taken. A 2-sample t test for independent samples was used to compare age between the 2 groups. Interrater reliability was assessed using the kappa (\u03ba) statistic. We used the guidelines proposed by \u2587\u2587\u2587\u2587\u2587\u2587 and \u2587\u2587\u2587\u2587 to interpret the level of agreement: \u03ba>0.80, excellent agreement; \u03ba=0.60 to 0.80, substantial agreement; \u03ba=0.40 to 0.60, moderate agreement; and \u03ba<0.40, poor to fair agreement (17). The following stroke subtypes were used: 1) large vessel, 2) cardioembolism, 3) small vessel, 4) other determined cause, and 5) undetermined cause. A sixth category\u2014no stroke/missing\u2014was included to account for instances in which reviewers did not provide a diagnosis. Reasons for missing data were not systematically collected. Separate estimates for \u03ba were obtained by treating the no stroke/missing category as missing data using the algorithm written by \u2587\u2587\u2587\u2587 et al (18). These analyses were repeated on the subset of the participants who self-reported having a stroke. \u2587\u2587\u2587\u2587\u2587\u2587\u2587 et al. Page 4 NIH-PA Author Manuscript The randomly sampled siblings in this study were screened for participation in SWISS between March 31, 2000, and November 6, 2003. The 30 siblings included were from 30 separate pedigrees. The probands of the siblings were enrolled at centers in 8 different states in the United States. Among the 30 siblings evaluated in this study, head computed tomography (CT) was performed on 80% (24/30) and MRI was performed on 60% (18/30). A cervical arterial imaging study (carotid ultrasonography, magnetic resonance angiography, or digital subtraction angiography) was performed on 97% (29/30). Intracranial arterial study (magnetic resonance angiography, digital subtraction angiography, CT angiography, or transcranial Doppler ultrasonography) was performed on 100% (30/30). Electrocardiography was performed on 73% (22/30). Cardiac ultrasonography (transthoracic or transesophageal) was performed on 67% (20/30). NIH-PA Author Manuscript Subject characteristics for the siblings included in this study are summarized in Table 1. The majority of subjects were male (67%) and white (83%). Ages ranged from 46 to 88 years, with a median of 70 years. Seventy-three percent smoked, 70% had hypertension, 27% had diabetes mellitus, 33% had chronic fibrillation, and 23% had had a myocardial infarction. The distributions of these characteristics did not differ significantly between the 30 siblings who were included in this study and the 101 concordant siblings who were not. The distribution of TOAST subtypes (based on the original SVC determination) for the siblings included in this study was 23% large vessel, 17% cardioembolic, 37% small vessel, 7% other cause, and 17% unknown cause. This distribution differed significantly from that of the unselected siblings because we purposely oversampled the cardioembolic cases. Responses on the QVSS were similar for the 2 groups (Table 2). The distribution of TOAST subtypes (Table 3) was similar for the large-vessel, cardioembolic, and other cause categories among the 6 reviewers. The distribution for the small-vessel, unknown cause, and no stroke/missing categories varied considerably. One reviewer had 2 missing values, another reviewer had 4 missing values, and a third reviewer had 10 missing values. The remaining reviewers had complete sets of readings. Excluding the original diagnoses made by the SVC, all 5 reviewers agreed on the diagnosis of stroke subtype in 37% (11/30) of siblings; 4 reviewers agreed on stroke subtype in 30% (9/30) of siblings; 3 or fewer reviewers agreed on the subtype diagnosis in 33% (10/30) of siblings. Reliability of the TOAST subtyping, as quantified by the \u03ba statistic, is summarized in Table NIH-PA Author Manuscript", "size": 1, "samples": [{"hash": "f1Iw7mApm4z", "uri": "/contracts/f1Iw7mApm4z#statistical-methods", "label": "Nih Pa Author Manuscript", "score": 25.96235466, "published": true}], "hash": "29e0d9a64fca0964f44a9943a90991bd", "id": 10}], "next_curs": "ClwSVmoVc35sYXdpbnNpZGVyY29udHJhY3RzcjgLEhZDbGF1c2VTbmlwcGV0R3JvdXBfdjU2IhxzdGF0aXN0aWNhbC1tZXRob2RzIzAwMDAwMDBhDKIBAmVuGAAgAA==", "clause": {"children": [["fractures-and-bmd-analysis", "Fractures and BMD Analysis"], ["procedures-for-reporting-deviations-to-original-statistical-analysis-plan", "Procedures for Reporting Deviations to Original Statistical Analysis Plan"], ["statistical-considerations", "Statistical Considerations"], ["safety-analysis", "Safety Analysis"], ["baseline-comparisons", "Baseline Comparisons"]], "parents": [["methods", "Methods"], ["coagulation", "Coagulation"], ["pregnancy", "Pregnancy\u200c"], ["final-provisions", "Final provisions"], ["rating-situation-in-the-biqmr-study", "Rating Situation in the BIQMR Study"]], "size": 43, "title": "Statistical Methods", "id": "statistical-methods", "related": [["statistical-data", "Statistical Data", "Statistical Data"], ["statistical-information", "Statistical Information", "Statistical Information"], ["statistical-demographic-or-market-related-data", "Statistical, Demographic or Market-Related Data", "Statistical, Demographic or Market-Related Data"], ["statistical-or-market-related-data", "Statistical or Market-Related Data", "Statistical or Market-Related Data"], ["statistical-and-market-data", "Statistical and Market Data", "Statistical and Market Data"]], "related_snippets": [], "updated": "2025-07-24T04:27:57+00:00"}, "json": true, "cursor": ""}}