ATLAS: an automated association test using probabilistically linked health records with application to genetic studies

Objective Large amounts of health data are becoming available for biomedical research. Synthesizing information across databases may capture more comprehensive pictures of patient health and enable novel research studies. When no gold standard mappings between patient records are available, researchers may probabilistically link records from separate databases and analyze the linked data. However, previous linked data inference methods are constrained to certain linkage settings and exhibit low power. Here, we present ATLAS, an automated, flexible, and robust association testing algorithm for probabilistically linked data. Materials and Methods Missing variables are imputed at various thresholds using a weighted average method that propagates uncertainty from probabilistic linkage. Next, estimated effect sizes are obtained using a generalized linear model. ATLAS then conducts the threshold combination test by optimally combining P values obtained from data imputed at varying thresholds using Fisher’s method and perturbation resampling. Results In simulations, ATLAS controls for type I error and exhibits high power compared to previous methods. In a real-world genetic association study, meta-analysis of ATLAS-enabled analyses on a linked cohort with analyses using an existing cohort yielded additional significant associations between rheumatoid arthritis genetic risk score and laboratory biomarkers. Discussion Weighted average imputation weathers false matches and increases contribution of true matches to mitigate linkage error-induced bias. The threshold combination test avoids arbitrarily choosing a threshold to rule a match, thus automating linked data-enabled analyses and preserving power. Conclusion ATLAS promises to enable novel and powerful research studies using linked data to capitalize on all available data sources.

Combined IFN-γ and IL-2 release assay for detect active pulmonary tuberculosis: a prospective multicentre diagnostic study in China

Background We performed a prospective multicentre diagnostic study to evaluate the combined interferon-γ (IFN-γ) and interleukin-2 (IL-2) release assay for detect active pulmonary tuberculosis (TB) in China. Methods Adult patients presenting symptoms suggestive of pulmonary TB were consecutively enrolled in three TB-specialized hospitals. Sputum specimens and blood sample and were collected from each participant at enrolment. The levels of Mycobacterium tuberculosis (MTB)-specific antigen-stimulated IFN-γ and IL-2 were determined using enzyme-linked immunosorbent assay (ELISA). Results Between July 2017 and December 2018, a total of 3245 patients with symptoms suggestive of pulmonary TB were included in final analysis. Of 3245 patients, 2536 were diagnosed as active TB, consisting of 1092 definite TB and 1444 clinically diagnosed TB. The overall sensitivity and specificity of IFN-γ were 83.8% and 81.5%, respectively. In addition, compared with IFN-γ, the specificity of IL-2 increased to 94.3%, while the sensitivity decreased to 72.6%. In addition, the highest sensitivity was achieved with parallel combination of IFN-γ/IL-2, with a sensitivity of 87.9%, and its overall specificity was 79.8%. The sensitivity of series combination test was 68.5%. Notably, the sensitivity of series combination test in definite TB (72.1%) was significantly higher than that in clinically diagnosed TB (65.8%). Conclusion In conclusion, we develop a new immunological method that can differentiate between active TB and other pulmonary diseases. Our data demonstrates that the various IFN-γ/IL-2 combinations provides promising alternatives for diagnosing active TB cases in different settings. Additionally, the diagnostic accuracy of series combination correlates with severity of disease in our cohort.

Evaluation of Geenius HIV-1/2 Confirmatory Assay for the confirmatory and differential diagnosis of HIV-1/HIV-2 in Japan and reliability of the Geenius Reader in the diagnosis of HIV-2

Background NEW LAV BLOT I and II (LAV I and LAV II), they were only option for human immunodeficiency virus (HIV) confirmatory test, following HIV screening test using HIV Ag/Ab combination test in Japan. We evaluated the performance of Geenius HIV-1/2 Confirmatory Assay (Geenius), both as a confirmatory test and for differentiation between HIV-1 and HIV-2, in comparison with LAV I and LAV II. Methods Eighty-nine HIV-1-positive plasma specimens, one anti-HIV-1 low-titer performance panel, 10 seroconversion panels, and two anti-HIV-1/2 combo performance panels were tested. The results were read with the Geenius Reader and by visual reading. Results All 89 HIV-1-positive plasma specimens were identified as HIV-1-positive using Geenius; this 100% success rate was superior to that with LAV I (95.5% using WHO criteria, 98.9% using CDC criteria). The HIV-1-positive specimens showed low cross-reactivity with HIV-2 lines in Geenius. The sensitivity of Geenius for HIV-1 detection was the same as or greater than that of LAV I, but less than that of Genscreen HIV Ag-Ab ULT, in our analysis of the commercial performance and seroconversion panels. In contrast, five of the 13 HIV-2-positive specimens that had been identified as HIV-positive untypable by visual reading because of their cross-reactivity to HIV-1 lines were successfully identified by the Geenius Reader as HIV-2-positive with cross-reactivity. Conclusions Geenius provides strong performance for HIV confirmatory tests and HIV-1 differentiation tests. However, when visual reading is used, its performance in HIV-2 differentiation is less reliable. Because HIV-2 infection has been sporadically reported in Japan, the use of the Geenius Reader is preferable to ensure more reliable HIV-1/HIV-2 differentiation.

Learning new verbs with known cue words: The relative effects of noun and adverb cues

Research has shown that learning a known-and-unknown word combination leads to greater learning than learning an unknown word alone (Kasahara, 2010, 2011). These studies found that attaching a known adjective to an unknown noun can help learners remember the unknown noun. Kasahara (2015) found that a known verb can serve as an effective cue to remember an unknown noun in a known-and-unknown combination. To examine useful cues to learn unknown verbs, this study compared verb (unknown) + noun (known) combinations to verb (unknown) + adverb (known) combinations. Additionally, we explored how learners’ vocabulary size would affect the known-and-unknown two-word combination learning to deepen our understanding of the characteristics of students who benefit from combination learning. The participants in each group learned 18 two-word combinations consisting of the same unknown target verbs and different known cues (nouns or adverbs). The participants were provided with a five-minute learning phase and two immediate recall tests: a Single Word Test, to write down the L1 meanings of the targets, and a Combination Test, to write down the L1 meanings of the combinations. The same two tests were administered one week later. The results showed that known nouns were better cues for learning unknown verbs than known adverbs. It was also found that participants with a larger vocabulary size benefited more from two-word combination learning.

Contrasts in fitness, motor competence and physical activity among children involved in single or multiple sports

Study aim: While there is wide debate around specialization in one sport, there is a lack of information about fitness levels and motor competence of children participating in single or multiple sports. Material and methods: The study involved 358 fifth-grade children who participated in a set of health-related fitness and motor competence tests over two consecutive years. A subsample of children (n = 109) wore an accelerometer for seven consecutive days. The independent samples t-test and ANCOVA were used to compare differences between single and multi-sport participants in study variables and changes between baseline and follow-up. Results: Multi-sport participants performed better in shuttle run (baseline/follow-up; p = 0.001/p = 0.006), push-up (p = 0.006/p = 0.036), and five leap tests (p = 0.001/p = 0.009) in baseline than single sport participants among boys. Likewise, multi-sport participants showed significantly more improvement in the throwing and catching combination test between study years among boys F1,159 = 3.570, p = 0.030. Among girls, no differences were found in any study variable between single and multi-sport participants. Conclusions: From the perspective of fitness and motor competence tests, there are no arguments for participating in just one sport at an early age. Instead, multi-sport participants performed better than single sport participants in the majority of test variables.

The Clinical Study of Multigene Combination Test to Guide Chemotherapy Combined with Targeted Therapy in Patients with Advanced Gastrointestinal Tumors

Objective: To study the clinical effects of multigene combination test to guide chemotherapy combined with targeted therapy in patients with advanced gastrointestinal tumors. Methods: The samples were selected from 60 patients with advanced gastrointestinal tumors admitted to our hospital from March 2019 to July 2020, and were divided into a study group and a control group using a random number table model; patients in the control group did not undergo genetic testing and FOLLOX4+PD-1 chemotherapy, while patients in the study group underwent TYMS, ERCC1, EGFR, and KRAS and VEGF gene expression levels test, and the sensitive treatment plan was determined based on the test results, and the clinical indexes were compared between the two groups. Results: By comparing the total effective rate, survival time, and time to disease progression of chemotherapy in the two groups, the study group has a significant advantage (P<0.05). Conclusion: The combination of chemotherapy and targeted therapy for advanced gastrointestinal tumor patients can improve the efficiency of chemotherapy and prolong the time of disease progression and survival, which is worthy of comprehensive promotion.

The behaviour of wine consumers towards organic wine: a statistical analysis through the non-parametric combination test

Purpose The purpose of this paper is to understand the relationship between consumers and organic wine purchases and how this production process can affect their willingness to pay a premium price. The aim of this paper is, therefore, to assess the role of organic attributes on the consumer’s choice, and how consumer socio-demographic characteristics influence the premium price for organic wine. Design/methodology/approach This survey represents the continuation of a paper already published by the same authors, which was aimed at identifying the factors that influence the preference and consumption of wine. The information about wine consumers was collected by the use of an ad hoc questionnaire, administered near very busy places, (supermarkets, main squares, theatres, universities and municipal offices) in a random way, within several municipalities in the province of Messina (Italy). The questionnaire, which was anonymous, was distributed directly with the face-to-face method. In total, 1,097 subjects compose the obtained sample. Among these, 459 subjects (42%) said they consumed organic wine, while the remaining 638 (58%) said they did not consume it. In this research, the non-parametric combination test is used, based on a permutation test, chosen for the several optimal properties which characterize it. Permutation tests represent an effective solution for problems concerning the testing of multidimensional hypotheses that are difficult to face in a parametric context. Findings The results obtained may have interesting implications for wineries in the prediction and choice of the company to convert traditional production into organic production, to meet new markets and new segments of consumers. In this direction, without any doubt, organic wines represent an opportunity for the wineries. Research limitations/implications Although field experiments are extremely useful for testing behavioural hypotheses, they are often limited by the small sample. Originality/value The originality of the research lies mainly in a deeper knowledge of organic wine consumption trends. The study carried out highlights how important it is to know which factors restrain consumers from buying wine so that companies can review their promotion and communication policies and, if possible, meet the needs of the market. The strength of this paper is the use of an adequate statistical instrument. This multivariate and multistrata procedure allows us to reach effective solutions concerning problems of multidimensional hypotheses verifying within the non-parametric permutation inference; it is used in different application fields that deal with the verifying of multidimensional hypotheses with a complexity that cannot be managed in a parametric context.

Combined IFN-γ and IL-2 Release Assay for Detect Active Pulmonary Tuberculosis: A Prospective Multicentre Diagnostic Study in China

Background: We performed a prospective multicenter diagnostic study to evaluate combined interferon-γ (IFN-γ) and interleukin-2 (IL-2) release assays for detecting active pulmonary tuberculosis (TB) in China. Methods: Adult patients presenting with symptoms suggestive of pulmonary TB were consecutively enrolled in three TB-specialized hospitals. Sputum specimens and blood samples were collected from each participant at enrollment. In vitro measurements of IFN-γ and IL-2 release from Mycobacterium tuberculosis (MTB)-specific antigen-stimulated patient peripheral blood mononuclear cells were conducted using enzyme-linked immunosorbent assays (ELISAs).Results: Between July 2017 and December 2018, a total of 3,245 patients with symptoms suggestive of pulmonary TB were included in the final analysis. Of these patients, 2,536 were diagnosed with active TB, including 1,092 definite and 1,444 clinically diagnosed cases. Overall sensitivity and specificity rates of the IFN-γ release assay were 83.8% and 81.5%, respectively, as compared to IL-2 assay rates yielding greater specificity (94.3%) but lower sensitivity (72.6%). Notably, a parallel-type combination test for IFN-γ/IL-2 provided greatest overall sensitivity (87.9%) but relatively low specificity (79.8%). Meanwhile, a series-type combination test had an overall sensitivity rate of 68.5% that, when stratified by case subgroup, yielded sensitivity rates of 72.1% and 65.8% for definite and clinically diagnosed TB cases, respectively.Conclusion: We developed a new immunological method to differentiate between active TB and other pulmonary diseases. Our data demonstrated that both series-type and parallel-type IFN-γ/IL-2 combination tests may improve diagnosis of active TB cases in different settings. Additionally, the diagnostic accuracy of the series-type combination assay correlated with disease severity in our patient cohort.