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To identify preoperative transabdominal sonographic predictors of surgically confirmed ovarian torsion (OT) in premenarchal girls We conducted a retrospective case-control study of 32 premenarchal girls aged 0-12 undergoing surgery for OT (cases) or a non-torsed ovarian mass (controls) from 2006 to 2017 at a single academic center. Cases had ICD-9/10 codes for torsion of the ovary, adnexa, ovarian pedicle, or fallopian tube and surgically confirmed OT; controls had codes for ovarian mass or cyst and surgically confirmed absence of OT. Preoperative transabdominal ultrasounds were analyzed by 3 radiologists blinded to final diagnosis. We used χ2, Fisher[s exact, and Student's t tests for statistical comparisons. From 2016 to 2017, 32 patients presented with acute abdominal pain or symptoms concerning for ovarian mass requiring ultrasound imaging and subsequent diagnostic laparoscopy; 24 (75.0%) had confirmed OT by laparoscopy, and 8 (25.0%) did not. The mean age in both groups was similar (7.3 ± 2.9 years). Preoperative sonographic variables significantly associated with OT included presence of a simple cyst (20.8% vs 12.5%), ovarian heterogeneity (100% vs 12.5%), presence of peripheralized follicles (70.8% vs 0%), and asymmetry of color Doppler (75.0% vs 37.5%; all P <.05). Presence of free fluid, arterial color Doppler, and a whirlpool sign were not predictive of OT. In premenarchal patients, although certain variables on transabdominal sonography predicted surgically confirmed OT, only the presence of peripheralized follicles was unique to girls with OT. The decision to proceed with diagnostic laparoscopy for suspected OT can be aided by these specific sonographic findings but should ultimately be based on high clinical suspicion. [ABSTRACT FROM AUTHOR]

Abstract Background Disability retirement has been investigated in the last two decades using predictors such as measures of sickness absence, psychological, social, and organizational work factors. The impact of various health-related and sickness measures on disability retirement across various occupational group reveal a significant relation. However, current literature lacks understanding in police personnel. Methods This study examines the roles of demographic and measures of sickness absence on disability retirement among police personnel in Abu Dhabi, UAE. The case–control design was used to predict disability retirement wherein controls were matched with cases according to age and gender from those who worked in the same administration as the case at baseline, to reduce the possible confounding influence of these variables. Conditional logistic regression models were used determine the odds-ratio of various measures of sickness absence in predicting disability retirement. Results Results indicate that increased number of spells, and number of days of sickness absence can predict disability retirements among police personnel in the UAE. Results indicate that odds ratios for disability retirement for the total exposure period increased from 1.76 (95% CI = 1.42-2.20) for spells of 4-7d to 2.47 (95%CI = 1.79-3.40) for spells of > 4 weeks. When compared with their married counterparts, non-married police employees had a statistically significant increase in odds of disability retirement of almost three fold (OR = 2.93, 95% CI = 1.55-5.56). Non-field and field police officers, on the other hand, had significantly reduced odds of disability retirement compared with admin/supportive staff (OR = 0.43 and 0.28 with 95% CI = 0.19-0.96 and 0.13-0.61 respectively). Odds ratios of disability retirement at end of the exposure period for the matching variables with those obtained after additionally adjusting for all demographic variables (model b), namely, marital status, occupation, employment grade and type, and educational level. The odds ratios of disability retirement remained significantly raised for the total number of days of sickness absence and for the number of spells of sickness absence for all spell types. Conclusions Recommendation to reduce the number of future disability retirements among Abu Dhabi Police include structured problem-solving process addressed through stepwise meetings between the line-managers and the employee.

Attention-deficit/hyperactivity disorder (ADHD) is highly heritable, but little is known about the relative effects of transmitted (i.e., direct) and nontransmitted (i.e., indirect) common variant risks. Using parent-offspring trios, we tested whether polygenic liability for neurodevelopmental and psychiatric disorders and lower cognitive ability is overtransmitted to ADHD probands. We also tested for indirect or genetic nurture effects by examining whether nontransmitted ADHD polygenic liability is elevated. Finally, we examined whether complete trios are representative of the clinical ADHD population. Polygenic risk scores (PRSs) for ADHD, anxiety, autism, bipolar disorder, depression, obsessive-compulsive disorder, schizophrenia, Tourette syndrome, and cognitive ability were calculated in UK control subjects (n = 5081), UK probands with ADHD (n = 857), their biological parents (n = 328 trios), and also a replication sample of 844 ADHD trios. ADHD PRSs were overtransmitted and cognitive ability and obsessive-compulsive disorder PRSs were undertransmitted. These results were independently replicated. Overtransmission of polygenic liability was not observed for other disorders. Nontransmitted alleles were not enriched for ADHD liability compared with control subjects. Probands from incomplete trios had more hyperactive-impulsive and conduct disorder symptoms, lower IQ, and lower socioeconomic status than complete trios. PRS did not vary by trio status. The results support direct transmission of polygenic liability for ADHD and cognitive ability from parents to offspring, but not for other neurodevelopmental/psychiatric disorders. They also suggest that nontransmitted neurodevelopmental/psychiatric parental alleles do not contribute indirectly to ADHD via genetic nurture. Furthermore, ascertainment of complete ADHD trios may be nonrandom, in terms of demographic and clinical factors. [ABSTRACT FROM AUTHOR]

Aims: This study was to assess the predictive ability of the Johns Hopkins Fall Risk Assessment Tool (Chinese Version) in inpatient settings. Design: A case–control study. Methods: This study was conducted in a tertiary hospital based on 2019 data. With a case–control design in a 1:2 ratio, the predictive ability of the Johns Hopkins Fall Risk Assessment Tool (Chinese Version) was determined by ROC curve. The best cut point was identified based on sensitivity, specificity, positive predict value and negative predict value. Conditional logistical regression analysis was conducted to test the predictive ability of each indicator. Results: The study included 309 patients, with 103 in the case group and 206 in the control groups. Generally, the predictive ability was acceptable with the area under ROC curve value at 0.73 (95% CI: 0.67–0.79). Positive predict value and negative predict value performed best at the cut point of 13. Sensitivity at cut point 6 was much higher than that at cut point 13, though specificity was lower. Except for age, all indicators in the Johns Hopkins Fall Risk Assessment Tool (Chinese Version) demonstrated significant predictive ability as to occurrence of fall. Conclusion: The Johns Hopkins Fall Risk Assessment Tool (Chinese Version) is a reliable assessment instrument in the inpatient settings. Impact This is the first study that evaluated the predictive ability of the Johns Hopkins Fall Risk Assessment Tool (Chinese version) in the inpatient settings, and proved that the instrument is reliable for assessing inpatient fall risks. Further studies could be carried out to assess the predict ability of Johns Hopkins Fall Risk Assessment Tool (Chinese version) among specific populations. [ABSTRACT FROM AUTHOR]

Abstract Background While random forests are one of the most successful machine learning methods, it is necessary to optimize their performance for use with datasets resulting from a two-phase sampling design with a small number of cases—a common situation in biomedical studies, which often have rare outcomes and covariates whose measurement is resource-intensive. Methods Using an immunologic marker dataset from a phase III HIV vaccine efficacy trial, we seek to optimize random forest prediction performance using combinations of variable screening, class balancing, weighting, and hyperparameter tuning. Results Our experiments show that while class balancing helps improve random forest prediction performance when variable screening is not applied, class balancing has a negative impact on performance in the presence of variable screening. The impact of the weighting similarly depends on whether variable screening is applied. Hyperparameter tuning is ineffective in situations with small sample sizes. We further show that random forests under-perform generalized linear models for some subsets of markers, and prediction performance on this dataset can be improved by stacking random forests and generalized linear models trained on different subsets of predictors, and that the extent of improvement depends critically on the dissimilarities between candidate learner predictions. Conclusion In small datasets from two-phase sampling design, variable screening and inverse sampling probability weighting are important for achieving good prediction performance of random forests. In addition, stacking random forests and simple linear models can offer improvements over random forests.

Background: Disability retirement has been investigated in the last two decades using predictors such as measures of sickness absence, psychological, social, and organizational work factors. The impact of various health-related and sickness measures on disability retirement across various occupational group reveal a significant relation. However, current literature lacks understanding in police personnel.Methods: This study examines the roles of demographic and measures of sickness absence on disability retirement among police personnel in Abu Dhabi, UAE. The case-control design was used to predict disability retirement wherein controls were matched with cases according to age and gender from those who worked in the same administration as the case at baseline, to reduce the possible confounding influence of these variables. Conditional logistic regression models were used determine the odds-ratio of various measures of sickness absence in predicting disability retirement.Results: Results indicate that increased number of spells, and number of days of sickness absence can predict disability retirements among police personnel in the UAE. Results indicate that odds ratios for disability retirement for the total exposure period increased from 1.76 (95% CI = 1.42-2.20) for spells of 4-7d to 2.47 (95%CI = 1.79-3.40) for spells of > 4 weeks. When compared with their married counterparts, non-married police employees had a statistically significant increase in odds of disability retirement of almost three fold (OR = 2.93, 95% CI = 1.55-5.56). Non-field and field police officers, on the other hand, had significantly reduced odds of disability retirement compared with admin/supportive staff (OR = 0.43 and 0.28 with 95% CI = 0.19-0.96 and 0.13-0.61 respectively). Odds ratios of disability retirement at end of the exposure period for the matching variables with those obtained after additionally adjusting for all demographic variables (model b), namely, marital status, occupation, employment grade and type, and educational level. The odds ratios of disability retirement remained significantly raised for the total number of days of sickness absence and for the number of spells of sickness absence for all spell types.Conclusions: Recommendation to reduce the number of future disability retirements among Abu Dhabi Police include structured problem-solving process addressed through stepwise meetings between the line-managers and the employee. [ABSTRACT FROM AUTHOR]

The outbreak of COVID‐19 has turned out to be a major challenge to societies all over the globe. Curbing the pandemic requires rapid and extensive behavioural change to limit social interaction, including physical distancing. In this study, we tested the notion that inducing empathy for people vulnerable to the virus may result in actual distancing behaviour beyond the mere motivation to do so. In a large field experiment with a sequential case–control design, we found that (a) empathy prompts may increase distancing as assessed by camera recordings and (b) effectiveness of prompts depends on the dynamics of the pandemic and associated public health policies. In sum, the present study demonstrates the potential of empathy‐generating interventions to promote pro‐social behaviour and emphasizes the necessity of field experiments to assess the role of context before advising policy makers to implement measures derived from behavioural science. Please refer to Supplementary Material to find this article's Community and Social Impact Statement [ABSTRACT FROM AUTHOR]

Physical educators tend to be perceived as teachers of a non-core, ancillary subject, meaning that they often contend with marginalization. In previous research, physical education National Board Certified Teachers (NBCTs) reported enhanced self-efficacy and confidence in their teaching with reduced feelings of marginality. Nevertheless, direct comparisons between the perceived workplace experiences of physical education NBCTs and non-NBCTs have not yet been made. The purpose of the current investigation was to examine the workplace experiences of physical education NBCTs and non-NBCTs while accounting for teaching level. A recruitment email was sent to 500 physical education NBCTs and 420 physical education non-NBCTs. Using a case–control design, 74 NBCTs were selected and matched with 74 non-NBCTs. A 2 × 2 factorial MANCOVA test, a univariate ANCOVA test, and an independent-samples t -test were used in data analysis. Results indicated that the main effect for NBCT status was significant. Specifically, NBCTs felt less isolated than their non-NBCTs counterparts. NBCTs generally perceived that they mattered more than non-NBCTs, especially at the secondary level. Additionally, teachers with NBCT certification reported higher levels of role conflict and role overload than those participants without NBCT status. This study highlights important connections between NBCT status and teachers' workplace experiences that both relate to and extend previous research. Future scholars should consider seeking to understand the mechanisms that underlie reported differences between NBCTs and non-NBCTs. [ABSTRACT FROM AUTHOR]

The purpose of this paper was to introduce the χ2 test for the data of four-fold tables collected from the case-control design， the hypothesis test and interval estimation of odds ratio， and the implementation of SAS and R software. In view of the characteristics of case-control design， the concept of odds ratio， hypothesis testing and interval estimation were emphasized. It was given that the interpretation of the results calculated by SAS and R software， as well as the statistical conclusion and professional.

Abstract Background The availability of large epidemiological or clinical data storing biological samples allow to study the prognostic value of novel biomarkers, but efficient designs are needed to select a subsample on which to measure them, for parsimony and economical reasons. Two-phase stratified sampling is a flexible approach to perform such sub-sampling, but literature on stratification variables to be used in the sampling and power evaluation is lacking especially for survival data. Methods We compared the performance of different sampling designs to assess the prognostic value of a new biomarker on a time-to-event endpoint, applying a Cox model weighted by the inverse of the empirical inclusion probability. Results Our simulation results suggest that case-control stratified (or post stratified) by a surrogate variable of the marker can yield higher performances than simple random, probability proportional to size, and case-control sampling. In the presence of high censoring rate, results showed an advantage of nested case-control and counter-matching designs in term of design effect, although the use of a fixed ratio between cases and controls might be disadvantageous. On real data on childhood acute lymphoblastic leukemia, we found that optimal sampling using pilot data is greatly efficient. Conclusions Our study suggests that, in our sample, case-control stratified by surrogate and nested case-control yield estimates and power comparable to estimates obtained in the full cohort while strongly decreasing the number of patients required. We recommend to plan the sample size and using sampling designs for exploration of novel biomarker in clinical cohort data.

Frequency matching is commonly used in epidemiological case control studies to balance the distributions of the matching factors between the case and control groups and to improve the efficiency of case‐control designs. Applied researchers have held a common opinion that unconditional logistic regression should be used to analyze frequency matched designs and conditional logistic regression is unnecessary. However, the justification of this view is unclear. To compare the performances of ULR and CLR in terms of simplicity, unbiasedness, and efficiency in a more intuitive way, we viewed frequency matching from the perspective of weighted sampling and derived the outcome models describing how the exposure and matching factors are associated with the outcome in the matched data separately in two scenarios: (1) only categorical variables are used for matching; (2) continuous variables are categorized for matching. In either scenario the derived outcome model is a logit model with stratum‐specific intercepts. Correctly specified unconditional logistic regression can be more efficient than conditional logistic regression, particularly when continuous matching factors are used, whereas conditional logistic regression is a more practical approach because it is less dependent on modeling choices. [ABSTRACT FROM AUTHOR]

Background: While random forests are one of the most successful machine learning methods, it is necessary to optimize their performance for use with datasets resulting from a two-phase sampling design with a small number of cases-a common situation in biomedical studies, which often have rare outcomes and covariates whose measurement is resource-intensive.Methods: Using an immunologic marker dataset from a phase III HIV vaccine efficacy trial, we seek to optimize random forest prediction performance using combinations of variable screening, class balancing, weighting, and hyperparameter tuning.Results: Our experiments show that while class balancing helps improve random forest prediction performance when variable screening is not applied, class balancing has a negative impact on performance in the presence of variable screening. The impact of the weighting similarly depends on whether variable screening is applied. Hyperparameter tuning is ineffective in situations with small sample sizes. We further show that random forests under-perform generalized linear models for some subsets of markers, and prediction performance on this dataset can be improved by stacking random forests and generalized linear models trained on different subsets of predictors, and that the extent of improvement depends critically on the dissimilarities between candidate learner predictions.Conclusion: In small datasets from two-phase sampling design, variable screening and inverse sampling probability weighting are important for achieving good prediction performance of random forests. In addition, stacking random forests and simple linear models can offer improvements over random forests. [ABSTRACT FROM AUTHOR]

Abstract Background Genome-wide association studies (GWAS) have identified more than 40 colorectal cancer susceptibility loci, but only a small fraction of heritability was explained. To account for missing heritability, we investigated gene-environment interactions (G × Es) between GWAS-identified single-nucleotide polymorphisms (SNPs) and established risk or protective factors for colorectal cancer using both case-only and case-control study designs. Methods Data on 703 colorectal cancer cases and 1406 healthy controls from the National Cancer Center in Korea were used. We tested interactions between 31 GWAS-identified SNPs and 13 established risk or protective factors for colorectal cancer (family history, body mass index, history of colorectal polyps, inflammatory bowel disease, and diabetes mellitus, alcohol drinking, smoking, regular exercise, regular aspirin use, postmenopausal hormone replace therapy, red meat and processed meat intake, and dairy consumption). Logistic regression models were used to assess G × Es for colorectal cancer risk. Results The SNP rs4444235 at 14q22.2 interacted with regular exercise in colorectal cancer (p case-only = 2.4 × 10− 3, p case-control = 1.5 × 10− 3). The risk allele (C) of rs4444235 increased the risk of colorectal cancer in regularly exercising individuals (OR = 1.47, 95% CI = 1.02–2.10) but decreased the risk in non-exercising individuals (OR = 0.76, 95% CI = 0.62–0.94). Furthermore, the G × E between the SNP rs2423279 at 20p12.3 and regular aspirin use was statistically significant (p case-only = 7.7 × 10− 3, p case-control = 1.6 × 10− 3). The additive effect of the risk allele (T) of rs2423279 on colorectal cancer risk was increased among regular aspirin users (OR = 4.62, 95% CI = 1.97–10.80). Conclusion Our results suggest that SNP rs4444235 at 14q22.2 and SNP rs2423279 at 20p12.3 may interact with regular exercise and aspirin use in colorectal carcinogenesis.

Longitudinal trajectories of vital signs and biomarkers during hospital admission of patients with COVID-19 remain poorly characterized despite their potential to provide critical insights about disease progression. We studied 1884 patients with severe acute respiratory syndrome coronavirus 2 infection from April 3, 2020, to June 25, 2020, within 1 Maryland hospital system and used a retrospective longitudinal framework with linear mixed-effects models to investigate relevant biomarker trajectories leading up to 3 critical outcomes: mechanical ventilation, discharge, and death. Trajectories of 4 vital signs (respiratory rate, ratio of oxygen saturation (Sp o 2) to fraction of inspired oxygen (Fi o 2), pulse, and temperature) and 4 laboratory values (C-reactive protein (CRP), absolute lymphocyte count (ALC), estimated glomerular filtration rate, and D-dimer) clearly distinguished the trajectories of patients with COVID-19. Before any ventilation, log(CRP), log(ALC), respiratory rate, and Sp o 2-to-Fi o 2 ratio trajectories diverge approximately 8–10 days before discharge or death. After ventilation, log(CRP), log(ALC), respiratory rate, Sp o 2-to-Fi o 2 ratio, and estimated glomerular filtration rate trajectories again diverge 10–20 days before death or discharge. Trajectories improved until discharge and remained unchanged or worsened until death. Our approach characterizes the distribution of biomarker trajectories leading up to competing outcomes of discharge versus death. Moving forward, this model can contribute to quantifying the joint probability of biomarkers and outcomes when provided clinical data up to a given moment. [ABSTRACT FROM AUTHOR]

Evaluating gene by environment (G × E) interaction under an additive risk model (i.e. additive interaction) has gained wider attention. Recently, statistical tests have been proposed for detecting additive interaction, utilizing an assumption on gene-environment (G-E) independence to boost power, that do not rely on restrictive genetic models such as dominant or recessive models. However, a major limitation of these methods is a sharp increase in type I error when this assumption is violated. Our goal was to develop a robust test for additive G × E interaction under the trend effect of genotype, applying an empirical Bayes-type shrinkage estimator of the relative excess risk due to interaction. The proposed method uses a set of constraints to impose the trend effect of genotype and builds an estimator that data-adaptively shrinks an estimator of relative excess risk due to interaction obtained under a general model for G-E dependence using a retrospective likelihood framework. Numerical study under varying levels of departures from G-E independence shows that the proposed method is robust against the violation of the independence assumption while providing an adequate balance between bias and efficiency compared with existing methods. We applied the proposed method to the genetic data of Alzheimer disease and lung cancer. [ABSTRACT FROM AUTHOR]

Causal effect identification considers whether an interventional probability distribution can be uniquely determined without parametric assumptions from measured source distributions and structural knowledge on the generating system. While complete graphical criteria and procedures exist for many identification problems, there are still challenging but important extensions that have not been considered in the literature such as combined transportability and selection bias, or multiple sources of selection bias. To tackle these new settings, we present a search algorithm directly over the rules of do-calculus. Due to the generality of do-calculus, the search is capable of taking more advanced datagenerating mechanisms into account along with an arbitrary type of both observational and experimental source distributions. The search is enhanced via a heuristic and search space reduction techniques. The approach, called do-search, is provably sound, and it is complete with respect to identifiability problems that have been shown to be completely characterized by do-calculus. When extended with additional rules, the search is capable of handling missing data problems as well. With the versatile search, we are able to approach new problems for which no other algorithmic solutions exist. We perform a systematic analysis of bivariate missing data problems and study causal inference under case-control design. We also present the R package dosearch that provides an interface for a C++ implementation of the search.

Abstract Background Skewed X chromosome inactivation (XCI), which is a non-random process, is frequently observed in both healthy and affected females. Furthermore, skewed XCI has been reported to be related to many X-linked diseases. However, no statistical method is available in the literature to measure the degree of the skewness of XCI for case-control design. Therefore, it is necessary to develop methods for such a task. Results In this article, we first proposed a statistical measure for the degree of XCI skewing by using a case-control design, which is a ratio of two logistic regression coefficients after a simple reparameterization. Based on the point estimate of the ratio, we further developed three types of confidence intervals (the likelihood ratio, Fieller’s and delta methods) to evaluate its variation. Simulation results demonstrated that the likelihood ratio method and the Fieller’s method have more accurate coverage probability and more balanced tail errors than the delta method. We also applied these proposed methods to analyze the Graves’ disease data for their practical use and found that rs3827440 probably undergoes a skewed XCI pattern with 68.7% of cells in heterozygous females having the risk allele T active, while the other 31.3% of cells keeping the normal allele C active. Conclusions For practical application, we suggest using the Fieller’s method in large samples due to the non-iterative computation procedure and using the LR method otherwise for its robustness despite its slightly heavy computational burden.

Background: The availability of large epidemiological or clinical data storing biological samples allow to study the prognostic value of novel biomarkers, but efficient designs are needed to select a subsample on which to measure them, for parsimony and economical reasons. Two-phase stratified sampling is a flexible approach to perform such sub-sampling, but literature on stratification variables to be used in the sampling and power evaluation is lacking especially for survival data.Methods: We compared the performance of different sampling designs to assess the prognostic value of a new biomarker on a time-to-event endpoint, applying a Cox model weighted by the inverse of the empirical inclusion probability.Results: Our simulation results suggest that case-control stratified (or post stratified) by a surrogate variable of the marker can yield higher performances than simple random, probability proportional to size, and case-control sampling. In the presence of high censoring rate, results showed an advantage of nested case-control and counter-matching designs in term of design effect, although the use of a fixed ratio between cases and controls might be disadvantageous. On real data on childhood acute lymphoblastic leukemia, we found that optimal sampling using pilot data is greatly efficient.Conclusions: Our study suggests that, in our sample, case-control stratified by surrogate and nested case-control yield estimates and power comparable to estimates obtained in the full cohort while strongly decreasing the number of patients required. We recommend to plan the sample size and using sampling designs for exploration of novel biomarker in clinical cohort data. [ABSTRACT FROM AUTHOR]

Several statistical methods have been proposed for testing gene-environment (G-E) interactions under additive risk models using data from genome-wide association studies. However, these approaches have strong assumptions from underlying genetic models, such as dominant or recessive effects that are known to be less robust when the true genetic model is unknown. We aimed to develop a robust trend test employing a likelihood ratio test for detecting G-E interaction under an additive risk model, while incorporating the G-E independence assumption to increase power. We used a constrained likelihood to impose 2 sets of constraints for: 1) the linear trend effect of genotype and 2) the additive joint effects of gene and environment. To incorporate the G-E independence assumption, a retrospective likelihood was used versus a standard prospective likelihood. Numerical investigation suggests that the proposed tests are more powerful than tests assuming dominant, recessive, or general models under various parameter settings and under both likelihoods. Incorporation of the independence assumption enhances efficiency by 2.5-fold. We applied the proposed methods to examine the gene-smoking interaction for lung cancer and gene–apolipoprotein E |$\varepsilon$| 4 interaction for Alzheimer disease, which identified 2 interactions between apolipoprotein E |$\varepsilon$| 4 and loci membrane-spanning 4-domains subfamily A (MS4A) and bridging integrator 1 (BIN1) genes at genome-wide significance that were replicated using independent data. [ABSTRACT FROM AUTHOR]

Toxicological studies have indicated that exposure to chlorinated paraffins (CPs) may disrupt intracellular glucose and energy metabolism. However, limited information exists regarding the impact of human CP exposure on glucose homeostasis and its potential association with an increased risk of developing gestational diabetes mellitus (GDM). Here, we conducted a prospective study with a nested case-control design to evaluate the link between short- and medium-chain CP (SCCPs and MCCPs) exposures during pregnancy and the risk of GDM. Serum samples from 102 GDM-diagnosed pregnant women and 204 healthy controls were collected in Hangzhou, Eastern China. The median (interquartile range, IQR) concentration of SCCPs was 161 (127, 236) ng/mL in the GDM group compared to 127 (96.9, 176) ng/mL in the non-GDM group ( p < 0.01). For MCCPs, the GDM group had a median concentration of 144 (117, 174) ng/mL, while the control group was 114 (78.1, 162) ng/mL ( p < 0.01). Compared to the lowest quartile as the reference, the adjusted odds ratios (ORs) of GDM were 7.07 (95% CI: 2.87, 17.40) and 3.34 (95% CI: 1.48, 7.53) in the highest quartile of ∑SCCP and ∑MCCP levels, respectively, with MCCPs demonstrating an inverted U-shaped association with GDM. Weighted quantile sum regression evaluated the joint effects of all CPs on GDM and glucose homeostasis. Among all CP congeners, C 13 H 23 Cl 5 and C 10 H 16 Cl 6 were the crucial variables driving the positive association with the GDM risk. Our results demonstrated a significant positive association between CP concentration in maternal serum and GDM risk, and exposure to SCCPs and MCCPs may disturb maternal glucose homeostasis. These findings contribute to a better understanding of the health risks of CP exposure and the role of environmental contaminants in the pathogenesis of GDM.

Aim: Based on metabonomics, the metabolic markers of lung cancer patients were analyzed, combined with bioinformatics to explore the underlying disease mechanism. Materials & methods: Based on case–control design, using UPLC-Q-TOF/MS, urine metabolites were detected in discovery and validation set. Multivariate statistical analysis were performed to identify potential markers for lung cancer. A network analysis was constructed to integrate lung cancer disease targets with the above metabolic markers, and its possible mechanism and biological significance were explained. Results: A total of 35 potential markers were identified, 11 of which overlapped. Five key markers have a good linear correlation with serum biochemical indicators. Conclusion: The occurrence and development of lung cancer are closely related to disturbance of D-Glutamine and D-glutamate metabolism, amino acid imbalance. This test was registered on China clinical trial registration center (www.chictr.org.cn/index.aspx), registration number was ChiCTR1900025543. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies (GWAS) have identified more than 40 colorectal cancer susceptibility loci, but only a small fraction of heritability was explained. To account for missing heritability, we investigated gene-environment interactions (G × Es) between GWAS-identified single-nucleotide polymorphisms (SNPs) and established risk or protective factors for colorectal cancer using both case-only and case-control study designs.Methods: Data on 703 colorectal cancer cases and 1406 healthy controls from the National Cancer Center in Korea were used. We tested interactions between 31 GWAS-identified SNPs and 13 established risk or protective factors for colorectal cancer (family history, body mass index, history of colorectal polyps, inflammatory bowel disease, and diabetes mellitus, alcohol drinking, smoking, regular exercise, regular aspirin use, postmenopausal hormone replace therapy, red meat and processed meat intake, and dairy consumption). Logistic regression models were used to assess G × Es for colorectal cancer risk.Results: The SNP rs4444235 at 14q22.2 interacted with regular exercise in colorectal cancer (pcase-only = 2.4 × 10- 3, pcase-control = 1.5 × 10- 3). The risk allele (C) of rs4444235 increased the risk of colorectal cancer in regularly exercising individuals (OR = 1.47, 95% CI = 1.02-2.10) but decreased the risk in non-exercising individuals (OR = 0.76, 95% CI = 0.62-0.94). Furthermore, the G × E between the SNP rs2423279 at 20p12.3 and regular aspirin use was statistically significant (pcase-only = 7.7 × 10- 3, pcase-control = 1.6 × 10- 3). The additive effect of the risk allele (T) of rs2423279 on colorectal cancer risk was increased among regular aspirin users (OR = 4.62, 95% CI = 1.97-10.80).Conclusion: Our results suggest that SNP rs4444235 at 14q22.2 and SNP rs2423279 at 20p12.3 may interact with regular exercise and aspirin use in colorectal carcinogenesis. [ABSTRACT FROM AUTHOR]

Use of a case-control design to compare the accuracy of two binary diagnostic tests is frequent in clinical practice. This design consists of applying the two diagnostic tests to all of the individuals in a sample of those who have the disease and in another sample of those who do not have the disease. This manuscript studies the comparison of the predictive values of two diagnostic tests subject to a case-control design. A global hypothesis test, based on the chi-square distribution, is proposed to compare the predictive values simultaneously, as well as other alternative methods. The hypothesis tests studied require knowing the prevalence of the disease. Simulation experiments were carried out to study the type I errors and the powers of the hypothesis tests proposed, as well as to study the effect of a misspecification of the prevalence on the asymptotic behavior of the hypothesis tests and on the estimators of the predictive values. The proposed global hypothesis test was extended to the situation in which there are more than two diagnostic tests. The results have been applied to the diagnosis of coronary disease.

Objective: Because benzodiazepines (BZDs) can affect pupillae muscles, their use could be a risk factor for acute angle-closure glaucoma (AACG), which is an ophthalmic emergency. However, there is no research evidence for the association between BZDs and AACG, except two case reports. We aimed to investigate whether BZDs increase the risk of AACG in a geriatric population.Methods: We performed a case-control study using a geriatric cohort from the National Health Insurance database (2002-2013) in Korea. Case subjects (n = 1117) were patients diagnosed with AACG. Controls, people who have not been diagnosed with AACG, were randomly matched with the case according to age, sex, and index year (n = 4468). To examine the risk of BZD use for AACG, we performed conditional logistic regression analyses with potential confounders including comorbidities and concomitant medication.Results: The use of BZD within 30 days was not significantly associated with AACG risk (adjusted odds ratio [aOR] = 1.14, 95% confidence interval [CI] = 0.94-1.37). Further analyses showed that, compared with non-use of BZD, new BZD use had a significantly increased risk for the development of AACG (aOR = 1.62, 95% CI = 1.09-2.37). The risk was higher in the new BZD users exposed within 7 days (aOR = 3.09, 95% CI = 1.58-5.88).Conclusion: We found that BZDs increase the risk of AACG at the beginning of its use among the Korean elderly. Clinicians should monitor visual disturbance in the elderly during the early period after prescription of BZD. [ABSTRACT FROM AUTHOR]

One important goal in pharmaco-epidemiology studies is to understand the causal relationship between drug exposures and their clinical outcomes, including adverse drug events. In order to achieve this goal, however, we need to resolve several challenges. Most of pharmaco-epidemiology data are observational and confounding is largely present due to many co-medications. The pharmaco-epidemiology study data set is often sampled from large medical record databases using a matched case-control design, and it may not be representative of the original patient population in the medical record databases. Data analysis method needs to handle a large sample size that cannot be handled using existing statistical analysis packages. In this paper, we tackle these challenges both methodologically and computationally. We propose a conditional causal log-odds ratio (OR) definition to characterize causal effects of drug exposures on a binary adverse drug event adjusting for individual level confounders. Using a case-control design, we present a propensity score estimation using only case samples and we provide sufficient conditions for the consistency of the estimation of the causal log-odds ratio using case-based propensity scores. Computationally, we implement a principle component analysis to reduce high-dimensional confounders. Extensive simulation studies are performed to demonstrate superior performance of our method to existing methods. Finally, we apply the proposed method to analyze drug-induced myopathy data sampled from a de-identified subset of medical record database (close to 5 million patient records), The Indiana Network for Patient Care. Our method identified 70 drug-induced myopathy (p < 0.05) out 72 drugs, which have myoathy side effects on their FDA drug labels. These 70 drugs include three statins who are known for their myopathy side effects. [ABSTRACT FROM AUTHOR]

• LLR vaccine is effective in preventing rotavirus disease in young children. • Vaccinated children are less likely to present severe clinical manifestations. • Receiving three doses of LLR vaccine in the first year of life should be preferred. Lanzhou Lamb rotavirus (LLR) vaccine was licensed in China in 2000. It was the only vaccine available in private market before 2018. However, the data about the post-marketing effectiveness is very limited. To assess the vaccine effectiveness (VE), we conducted a case-control study based on the hospital surveillance system in Beijing from 2015 to 2017. Seven hospitals located in seven districts in Beijing, from October 1, 2015, to March 31, 2017, were included. The VE of LLR vaccine was assessed in laboratory-confirmed rotavirus infection among children younger than five years old through a case-control design, using rotavirus-negative cases as controls. LLR vaccination was documented from a vaccination registry. VE was estimated adjusting for age group, gender, study site, the month of illness onset and interval days between illness onset to sampling through a logistic regression model. A total of 598 cases and 1766 controls were included in this study. The vaccine average coverage rate during 2015–2017 among children younger than five years old was 10.8% in Beijing. The adjusted VE for LLR vaccine of 1 dose versus 0 dose was 34.9% (95%CI, 5.3–55.3). We also obtained the adjusted VE of 87.7% (95%CI, 32.7–97.8) for patients with the severity score ≥11, 36.2% (95%CI, 4.7–57.3) for children of 2–35 months age group and 40.8% (95%CI, 7.8–61.9) against G9 rotavirus infection. Vaccinated cases were less likely to have watery stool (OR = 0.42) and have diarrhea longer than 5 days (OR = 0.47) than unvaccinated cases. LLR vaccine conferred protection against rotavirus disease. Children who were vaccinated presented with less severe clinical manifestations. An immunization schedule of receiving all three doses in the first year should be preferred. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The objective of this paper is to show the benefits of using a 2-phase case–control (2PCC) design in identifying dose–response relationships between cumulative occupational exposure as assessed by experts and lung cancer incidence in an actual study. METHODS: A population-based case–control study including 246 cases and 531 controls was conducted in an area with high lung cancer rates in Northeast France. Detailed occupational and personal risk factors were obtained in face-to-face interviews. Cumulative expert-based exposure scores were obtained from a subset of 215 cases and 269 controls stratified on smoking and a prior algorithmic exposure score for asbestos, crystalline silica, and polycyclic aromatic hydrocarbons (PAH) in the framework of a 2PCC design. This subset deliberately under-sampled large strata among controls but not among cases. Logistic regression models adapted to 2PCC studies were applied and corresponding computations of attributable fractions and their confidence intervals developed. RESULTS: Based on this 2PCC design, statistically significant dose–response relationships were obtained for asbestos, crystalline silica, PAH, and diesel motor exhaust. Simulations within this study showed that 2PCC studies were always more powerful than random samples. CONCLUSION: The 2PCC design may be the design of choice when resources allow only a limited number of subjects with a full expert-based exposure assessment.

Background The purpose of this study was to assess the cross-sectional area of the anconeus epitrochlearis muscle (AEM), cubital tunnel, and ulnar nerve with the elbow in extension in patients with and without ulnar neuropathy. Methods We performed a retrospective, level IV review of elbow magnetic resonance imaging (MRI) studies. Elbow MRI studies of 32 patients with an AEM (26 men and 6 women, aged 18-60 years), 32 randomly selected patients without an AEM (aged 16-71 years), and 32 patients with clinical ulnar neuritis (22 men and 10 women, aged 24-76 years) were reviewed. We evaluated the ulnar nerve cross-sectional area proximal to, within, and distal to the cubital tunnel; AEM cross-sectional area; and cubital tunnel cross-sectional area. Results We found no significant difference in the nerve caliber between patients with and without an AEM. No correlation was found between the AEM cross-sectional area and ulnar nerve cross-sectional area within the cubital tunnel ( r  = 0.14). The mean cubital tunnel cross-sectional area was larger in patients with an AEM. Only 4 of the 32 patients with an AEM had findings of ulnar neuritis on MRI. Of the 32 patients with a clinical diagnosis of ulnar neuritis, only 2 had an AEM. Conclusions With the elbow in extension, the presence or cross-sectional area of an AEM does not correlate with the area of the ulnar nerve or cubital tunnel. Only a small number of individuals with MRI evidence of an AEM had clinical evidence of ulnar neuropathy. Likewise, MRI evidence of an AEM was found in only a small number of individuals with clinical evidence of ulnar neuropathy. [ABSTRACT FROM AUTHOR]

Case-control studies are commonly used in epidemiology due to ease of handling and fast outcomes. However, insufficient matching and non-representative sampling are important problems with a significant effect (bias) on study results The goal of this study was to reanalyze the data from a case-control study to adjust control selection bias in the estimation of the associations of several demographic and pregnancy related factors (multiple pregnancy, menopause, and OCP consumption) with cardiovascular diseases (CVDs). To achieve this, census data was used as external (population based) data. In the present study, the distribution of the study variables among case and controls, and index variables (age and education) among cases, controls and a random sample of the source population are compared. Also, results of logistic regression analysis (LRA) are compared with those obtained from Bayesian post stratification analysis (BPSA). Results of LRA indicated significant associations between gravidity (OR=2.43,95% CI: 1.46 to 4.04), hypertension (OR=2.47,95% CI: 1.68 to 3.64), hyperlipidemia (OR=1.87,95% CI: 1.27 to 2.75) and CVD. According to the results from BPSA, the only significant association was found between hypertension (OR= 1.67, 95% CI: 1.07 to 2.62) and CVD. In addition, both methods of analysis revealed no significant associations between two important study variables i.e. menopause (OR=0.94, 95% CI: 0.66 to 1.35) and OCP consumption (OR=1.24, 95% CI: 0.83 to 1.86) and CVDs. The results of BPSA showed that frequent pregnancy, menopause and using OCP have no effect on CVDs, whereas LRA found a significant association between the number of pregnancies and CVDs. The results suggest that at least a part of the observed contradiction between the results of case-control studies are possibly due to selection bias. [ABSTRACT FROM AUTHOR]

Background The etiology of tennis elbow is multifactorial. Overuse of the wrist extensors along with anatomic factors, such as flexibility problems, aging, and poor blood circulation, may play a role. This study investigated whether patients with tennis elbow have a different psychological profile compared with healthy controls. Methods Patients with clinical signs of tennis elbow, consulting at the Ghent University Hospital between September 2015 and January 2017, were offered a paper-and-pencil questionnaire about Big Five personality traits, perfectionism, anxiety, depression, work satisfaction, and working conditions. Healthy controls in the same risk group were offered the same questionnaires. Results We recruited 69 patients (35 men, 34 women) and 100 controls (44 men, 56 women). Tennis elbow patients scored significantly lower on the personality traits extraversion and agreeableness. Men, in particular, scored significantly higher on perfectionism and were more likely to develop an anxiety disorder or a depression. Concerning work, patients indicated a significantly higher workload (especially men) and a significantly lower autonomy (especially women). Female patients also indicated less contact with colleagues. However, work satisfaction was relatively high in both groups. Conclusion The results suggest that there is a relationship between complaints related to tennis elbow and psychological characteristics. [ABSTRACT FROM AUTHOR]

Background Shoulder dislocation is often the first symptom of Ehlers-Danlos syndrome (EDS). Whether it occurs in early-onset EDS is unknown. In most cases, surgical failure leads to the diagnosis. We aimed to determine whether clinical symptoms can signal the presence of EDS at a first dislocation. Materials and methods In this retrospective study, we analyzed clinical and radiologic data for 27 patients with EDS and shoulder instability and a control population of 40 consecutive non-EDS patients undergoing surgery for an unstable shoulder. Data were collected on gender, age, single or bilateral disease, general hyperlaxity, shoulder hyperlaxity, number of dislocations or subluxations, nontraumatic onset, and pain specificity. Nerve and vascular injuries, joint disorders, and family history were recorded, and radiologic data were reported. Results Age <14 years, female sex, bilateral disorder, and general hyperlaxity were significantly more frequent in patients with EDS and a first dislocation than in those without EDS. Painless dislocation with pain after dislocation and concomitant nerve injury were more frequent in affected patients, as were hemostasis disorders and a family history of joint hyperlaxity. Bone lesions were not seen on radiographs. Only the hyperlaxity sign (external rotation >85°) did not differ between the groups. Conclusion After a first dislocation in a young girl with global hyperlaxity but not necessarily shoulder hyperlaxity, painless atraumatic dislocation with pain after reduction can suggest EDS. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess whether long-term administration of hydroxychloroquine (HCQ) is protective from influenza in patients with rheumatoid arthritis and systemic lupus erythematosus. Using a propensity score-matched design, patients who were prescribed HCQ for more than 10 months were matched with patients of the same gender, age group, and Charlson Comorbidity Index score who did not receive HCQ. A logistic regression model was used to estimate the association between the HCQ exposure and influenza after adjusting for covariates. We found no evidence that long-term HCQ exposure can provide a protective effect against influenza during an influenza season. [ABSTRACT FROM AUTHOR]

The shared family environment is an important risk factor in the development of childhood obesity. This study aims to examine differences in maternal psychopathology, family functioning, expressed emotion and coping skills between families of a child with obesity and those with a normal-weight child. This case-control study consisted of 50 mothers with a child (age 8-12 years) with obesity ( p ≥ 97) and a control group of 50 mothers of a child with normal weight ( p < 85), matched for age, sex and socio-economic status. Compared with families with normal-weight children, those with children with obesity showed significant differences in levels of trait anxiety, criticism and over-protectiveness, and maladaptive coping skills. Structural equation modelling revealed that the mothers' psychopathology predicted children's body mass index (BMI) z-scores through expressed emotion and maladaptive coping scores. There were significant direct and indirect relations among maternal BMI, psychopathology, expressed emotion and coping, which all together explained 26.5% of variance of children's BMI z-scores. Considering this relation between maternal variables and child weight status, childhood obesity intervention programs may benefit from targeting maternal BMI, psychopathology, expressed emotion and coping skills. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. [ABSTRACT FROM AUTHOR]

For over a decade functional gene-to-gene interaction (epistasis) has been suspected to be a determinant in the "missing heritability" of complex traits. However, searching for epistasis on the genome-wide scale has been challenging due to the prohibitively large number of tests which result in a serious loss of statistical power as well as computational challenges. In this article, we propose a two-stage method applicable to existing case-control data sets, which aims to lessen both of these problems by pre-assessing whether a candidate pair of genetic loci is involved in epistasis before it is actually tested for interaction with respect to a complex phenotype. The pre-assessment is based on a two-locus genotype independence test performed in the sample of cases. Only the pairs of loci that exhibit non-equilibrium frequencies are analyzed via a logistic regression score test, thereby reducing the multiple testing burden. Since only the computationally simple independence tests are performed for all pairs of loci while the more demanding score tests are restricted to the most promising pairs, genome-wide association study (GWAS) for epistasis becomes feasible. By design our method provides strong control of the type I error. Its favourable power properties especially under the practically relevant misspecification of the interaction model are illustrated. Ready-to-use software is available. Using the method we analyzed Parkinson's disease in four cohorts and identified possible interactions within several SNP pairs in multiple cohorts. [ABSTRACT FROM AUTHOR]

Background Expediting rotator cuff surgery is expected to facilitate recovery and return to work in injured workers. This case-control study examined the effect of expedited rotator cuff surgery on recovery and work status in injured workers. Materials and methods Injured workers who had undergone an expedited rotator cuff surgery funded by parallel-pay insurance (study group) were compared with workers who had used the public health insurance (control group) while adjusting for sex, age, severity of pathology, and follow-up period. Disability was measured by the American Shoulder and Elbow Surgeons (ASES) Standardized Assessment Form score. The percentage of patients who exceeded the minimal clinically important difference of 17 points in the ASES was calculated. Results The study group waited less time to have surgery than the control group ( P  < .0001), reported less disability after surgery, and had a higher number of patients whose improvement exceeded the minimal clinically important difference (119 vs. 65, P  < .0001). The study group was more likely to be working at the time of the final follow-up ( P  < .0001). The final multivariable regressions, which adjusted for unmatched variables, such as dominant side involvement, mechanism of injury, and associated operations that were different between groups, were consistent with univariable analyses indicating superior results in the study group. Conclusions Injured workers who underwent expedited rotator cuff surgery reported less disability and had a more successful return to work after surgery than injured workers who waited longer for specialist assessment and surgery within the public health system. [ABSTRACT FROM AUTHOR]

Background The literature has shown an increased complication rate with a delay to surgical repair of acute distal biceps tendon ruptures; however, little has been documented regarding the outcome of delayed repairs. This case-control study compared a study cohort of delayed (>21 days) distal biceps tendon repairs with a control cohort repaired acutely (<21 days). Methods Sixteen delayed repair cases were reviewed and matched with acute controls (1:3) based on repair technique, age, and workers' compensation status. The delayed cohort was reviewed and completed isometric strength testing and the Disabilities of the Arm, Shoulder and Hand questionnaire; Patient-Rated Elbow Evaluation; and American Shoulder and Elbow Surgeons elbow questionnaire. Results The time to surgery averaged 37 ± 12 days in the delayed cohort versus 10 ± 6 days in the acute cohort. Complications occurred in 63% of patients in the delayed cohort versus 29% in the acute cohort ( P  = .04); however, 90% of the delayed cohort's complications consisted of transient paresthesias. Follow-up scores on the Patient-Rated Elbow Evaluation, Disabilities of the Arm, Shoulder and Hand questionnaire, and American Shoulder and Elbow Surgeons elbow questionnaire were not statistically different between cohorts ( P  > .37, P  > .22, and P  > .46, respectively). Conclusions Despite a high rate of initial complications, patients treated with distal biceps tendon repair after a delay (>21 days) can expect similar functional outcomes to those treated acutely. [ABSTRACT FROM AUTHOR]

Case–control design to assess the accuracy of a binary diagnostic test (BDT) is very frequent in clinical practice. This design consists of applying the diagnostic test to all of the individuals in a sample of those who have the disease and in another sample of those who do not have the disease. The sensitivity of the diagnostic test is estimated from the case sample and the specificity is estimated from the control sample. Another parameter which is used to assess the performance of a BDT is the weighted kappa coefficient. The weighted kappa coefficient depends on the sensitivity and specificity of the diagnostic test, on the disease prevalence and on the weighting index. In this article, confidence intervals are studied for the weighted kappa coefficient subject to a case–control design and a method is proposed to calculate the sample sizes to estimate this parameter. The results obtained were applied to a real example. [ABSTRACT FROM PUBLISHER]

Summary Background & aims Few studies were available in exploring the roles of dietary patterns in the development of esophageal cancer, especially in China. This study aimed to investigate the roles of dietary patterns in the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese rural population. Methods A population-based cases–control study was designed and conducted in Yanting County, Sichuan Province of China during two years (between June 2011 and May 2013). A total of 942 pairs of ESCC cases and controls were recruited. A food frequency questionnaire was adopted to collect information of dietary consumption. Dietary patterns were extracted by using principle component and factor analysis based on 24 dietary groups. Odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated by using logistic regression model, with adjustment for possible confounding variables. Results Four major dietary patterns were identified, which were labeled as “prudent”, “vegetable and fruits”, “processed food” and “alcohol drinking”. In comparison of the highest with the lowest quartiles of pattern scores, the processed food pattern (OR: 2.84, 95% CI: 2.13–3.80) and alcohol drinking pattern (OR: 2.69, 95% CI: 1.95–3.71) were significantly associated with an increased risk of ESCC, while the vegetable and fruit pattern (OR: 0.70, 95% CI: 0.53–0.92) was associated with reduced risk by 30%. The prudent pattern was associated with a reduced risk by 33% (OR: 0.67, 95% CI: 0.50–0.88) in a multivariate logistic regression model, but no statistical significance was reached in a composite model. Conclusions The results suggest an important role of dietary patterns in ESCC. Diets rich in vegetables and fruits may decrease the risk of ESCC, whereas diets rich in processed food and drinking alcohol may increase the risk. [ABSTRACT FROM AUTHOR]

We develop a transport formula for predicting overall cumulative vaccine efficacy through time t (VE(t)) to prevent clinically significant infection with a genetically diverse pathogen (e. g., HIV infection) in a new setting for which a Phase III preventive vaccine efficacy trial that would directly estimate VE(t) has not yet been conducted. The formula integrates data from (1) a previous Phase III trial, (2) a Phase I/II immune response biomarker endpoint trial in the new setting where a follow-up Phase III trial is planned, (3) epidemiological data on background HIV infection incidence in the new setting; and (4) genomic epidemiological data on HIV sequence distributions in the previous and new settings. For (1), the randomized vaccine versus placebo Phase III trial yields estimates of vaccine efficacy to prevent particular genotypes of HIV in participant subgroups defined by baseline covariates X and immune responses to vaccination Sð1Þ measured at a fixed time point τ (potential outcomes if assigned vaccine); often one or more immune responses to vaccination are available that modify genotype-specific vaccine efficacy. The formula focuses on subgroups defined by X and Sð1Þ and being at-risk for HIV infection at τ under both the vaccine and placebo treatment assignments. For (2), the Phase I/II trial tests the same vaccine in a new setting, or a refined new vaccine in the same or new setting, and measures the same baseline covariates and immune responses as the original Phase III trial. For (3), epidemiological data in the new setting are used to project overall background HIV infection rates in the baseline covariate subgroups in the planned Phase III trial, hence re-calibrating for HIV incidence differences in the two settings; whereas for (4), data bases of HIV sequences measured from HIV infected individuals are used to re-calibrate for differences in the distributions of the circulating HIV genotypes in the two settings. The transport formula incorporates a user-specified bridging assumption function that measures differences in HIV genotype-specific conditional biological-susceptibility vaccine efficacies in the two settings, facilitating a sensitivity analysis. We illustrate the transport formula with application to HIV Vaccine Trials Network (HVTN) research. One application of the transport formula is to use predicted VE(t) as a rational criterion for ranking a set of candidate vaccines being studied in Phase I/II trials for their priority for down-selection into the follow-up Phase III trial. [ABSTRACT FROM AUTHOR]

Background The strength of the shoulder protractors and retractors may be compromised in individuals with winged scapula (IwWS). However, no standard approach to measuring the strength of these muscles has been described. The aim of this study was to study the intra-rater and inter-rater reproducibility of a fixed-base isometric dynamometer and to describe cutoff scores for clinically meaningful change for protraction and retraction isometric strength. Method Twice during a week, 20 normal subjects and 20 IwWS were tested by 2 independent raters. Results IwWS were significantly weaker ( P  < .001) than control subjects in their protraction and retraction isometric strength. Excellent intra-rater and inter-rater correlations were obtained in most combinations, leading to low cutoff scores for meaningful change expressed in terms of the smallest real difference. Conclusion When it is properly used, the technique described in this paper is recommended as an effective clinical tool for the quantitative assessment of protraction and retraction isometric strength, both for status determination and for monitoring of change in IwWS during and after rehabilitation. [ABSTRACT FROM AUTHOR]

South Denpasar District was of there as with the highest dengue cases in Bali province. The number of mosquito breeding places and larvae density become risk factor that influenced the spreading of mosquitoes. Maya index was an indicator to measure the amount of water reservoirs can be breeding places for mosquitoes. Knowing the relationship between maya index and density of larvae and pupae of Ae.aegypti toward dengue infection in South Denpasar District. The study was observational analytic with case-control design. Data was collected through interviews and field observations to 150 respondents. The survey entomologist with indicators maya index, house index (HI), container index (CI), breteau index (BI) and pupa index (PI) to see the density of larvae and pupae in survey area. Dengue transmission risk was categorized mild, moderate and severe based on density figure. Water storage containers inspected in 1215 containers that as many as 675 containers in the case and 540 containers in control. Water reservoirs (TPA) that the most larvae was tub (29.27%), dispenser (18.29%), container tirta (10.98%), wells (10.98%). Maya index status was lower in the case (24%) smaller than controls (37.33%). Value of HI = 23.33; CI=10.69; BI=55; PI=15.33. Based on HI and CI indicator South Denpasar District means have moderate the risk of transmission spread of dengue disease. Based on the BI, have a high risk of transmission to the spread of dengue disease. Based on the maya index showed house cases have highest risk as breeding place compare than control house. House index, Breteau index, container index, pupa index and maya index have correlation with dengue infection. Kind of breeding place have the high risk is bath tub.

In a randomized controlled clinical trial that assesses treatment efficacy, a common objective is to assess the association of a measured biomarker response endpoint with the primary study endpoint in the active treatment group, using a case-cohort, case-control, or two-phase sampling design. Methods for power and sample size calculations for such biomarker association analyses typically do not account for the level of treatment efficacy, precluding interpretation of the biomarker association results in terms of biomarker effect modification of treatment efficacy, with detriment that the power calculations may tacitly and inadvertently assume that the treatment harms some study participants. We develop power and sample size methods accounting for this issue, and the methods also account for inter-individual variability of the biomarker that is not biologically relevant (e.g., due to technical measurement error). We focus on a binary study endpoint and on a biomarker subject to measurement error that is normally distributed or categorical with two or three levels. We illustrate the methods with preventive HIV vaccine efficacy trials and include an R package implementing the methods. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]