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Background: The efficacy and safety of conversion surgery (CS) after FOLFIRINOX or gemcitabine plus nab‐paclitaxel (GnP) chemotherapy in patients with initially unresectable pancreatic cancer (PC) remains unclear. Methods: This multicenter retrospective cohort study enrolled patients, between 2014 and 2018, with initially locally advanced or metastatic PC who were considered candidates for CS following FOLFIRINOX or GnP chemotherapy. They were classified into surgery (207 patients [194 resection and 13 exploratory laparotomy only]) and continued chemotherapy (10 patients, control) groups. The primary endpoint was overall survival (OS) from the day of diagnosis of potentially curative resection on imaging studies, with an expected hazard ratio (HR) of 0.7. Results: OS in the surgery group was longer than that in the control group (HR, 0.47; 95% confidence interval [CI]: 0.24–0.93). The median OS was 34.4 (95% CI: 27.9–43.4) and 19.8 (95% CI: 14.9–31.1) months in the surgery and control groups, respectively. The Clavien‐Dindo grade ≥ IIIa postoperative complication and in‐hospital mortality rates were 19.6% and 0.5%, respectively. Multivariate analysis revealed that preoperative chemotherapy duration was not associated with OS. Conclusions: CS, following a favorable response to FOLFIRINOX or GnP chemotherapy, improved initially unresectable PC prognosis (specifically, OS), regardless of the chemotherapy duration. [ABSTRACT FROM AUTHOR]

Objective: Over the past decade, liquid‐based cytology has replaced conventional cytology for cervical cancer screening in many countries, including Japan. We aimed to evaluate the efficacy of liquid‐based cytology using a large database and compare two major liquid‐based cytology platforms, SurePath and ThinPrep, to conventional cytology. Methods: Cervical cancer screening data were collected from the Japan Cancer Society between 2015 and 2019. The efficacy of liquid‐based and conventional cytology in detecting cervical intraepithelial neoplasia (CIN) was evaluated. Detection rates and positive predictive values were compared using a Poisson regression model. Results: We collected data of 3,918,149 participants, including 2,248,202 conventional cytology, 874,807 SurePath and 795,140 ThinPrep smears. The detection rate of CIN2 or more was 1.14 times higher using SurePath than that using conventional cytology (95% confidence interval [CI], 1.09–1.20; p < 0.001). Contrastingly, the detection rate of CIN2 or more was 0.91 times lower using ThinPrep (95% CI, 0.86–0.96; p < 0.001). The detection rates of CIN3 or more did not differ significantly between SurePath and conventional cytology (detection rate ratio, 1.04; 95% CI, 0.97–1.12; p = 0.224). The positive predictive value ratios of CIN2 or more were 0.80 using SurePath (95% CI, 0.76–0.84; p < 0.001) and 0.83 using ThinPrep (95% CI, 0.79–0.87; p < 0.001) compared with conventional cytology. Conclusions: Liquid‐based cytology, particularly SurePath, was useful for detecting CIN2 or higher in population‐based cervical cancer screening. Further widespread use of liquid‐based cytology methods would lead to efficient detection of cervical precancerous lesions. [ABSTRACT FROM AUTHOR]

Positive and negative predictive values are useful to quantify the performance of medical tests, and both are often used simultaneously. Although there are several methods to test the equality of these predictive values between two medical tests, these approaches separately compare positive and negative predictive values. Therefore, we propose a testing procedure that combines the approximate likelihood ratio test defined by Tang et al. with the non-inferiority test for predictive values. The procedure can confirm that compared to an existing test, a new medical test is non-inferior in terms of both positive and negative predictive values, as well as superior regarding at least one of these values. It can make a comprehensive judgment of the performance of the new test based on both measures. A simulation study showed that the performance of the proposed testing procedure is appropriate, and the procedure is considered useful for evaluating the performance of predictive values of medical tests. [ABSTRACT FROM AUTHOR]

In some situations, square contingency tables with ordered categories are analyzed by considering collapsed tables where adjacent categories are combined. This study proposes measures to represent the degree of departure from symmetry using collapsed tables. The proposed measures are defined as the arithmetic mean of submeasures of each collapsed 3 × 3 table. Additionally, a theorem affirms that the value of the measure for symmetry is equal to the sum of the value of the proposed measures. Finally, examples are given. [ABSTRACT FROM AUTHOR]

This study deals with square contingency tables, which are two-way contingency tables in which the row and column variables consist of the same classification. When the categorical variables are grouped into ordered categories from quantitative variables by cut points, a score that approximates the distance between the midpoints of the quantitative scale categories may be used to reflect the characteristics of the data. As an asymmetry model based on scores, this study proposes the cumulative ordinal quasi-symmetry model and ordinal marginal homogeneity model based on cumulative probabilities. The asymmetric parameter in the proposed models would be useful for making inferences such as that a row variable is stochastically less than a column variable or vice versa. This study also gives a separation of the cumulative ordinal quasi-symmetry model, that is, the cumulative ordinal quasi-symmetry model holds if and only if both the cumulative quasi-symmetry and ordinal marginal homogeneity models hold. The usefulness of the proposed models and the proposed separation is demonstrated through real data analysis. [ABSTRACT FROM AUTHOR]

This study retrospectively evaluated the mid-term outcomes of surgical aortic valve replacement (SAVR) using a stented porcine aortic valve bioprosthesis (Mosaic; Medtronic Inc., Minneapolis, MN, USA) with concomitant mitral valve (MV) repair. From 1999 to 2014, 157 patients (median [interquartile range] age, 75 [70–79] years; 47% women) underwent SAVR with concomitant MV repair (SAVR + MV repair), and 1045 patients (median [interquartile range] age, 76 [70–80] years; 54% women) underwent SAVR only at 10 centers in Japan as part of the long-term multicenter Japan Mosaic valve (J-MOVE) study. The 5-year overall survival rate was 81.5% ± 4.1% in the SAVR + MV repair group and 85.1% ± 1.4% in the SAVR only group, and the 8-year overall survival rates were 75.2% ± 5.7% and 78.1% ± 2.1%, respectively. Cox proportional hazards analysis showed no significant difference in the survival rates between the two groups (hazard ratio, 0.87; 95% confidence interval, 0.54–1.40; P = 0.576). Among women with mild or moderate mitral regurgitation who were not receiving dialysis, those who underwent SAVR + MV repair, were aged > 75 years, and had a preoperative left ventricular ejection fraction of 30–75% tended to have a lower mortality risk. In conclusion, this subgroup analysis of the J-MOVE cohort showed relevant mid-term outcomes after SAVR + MV repair. [ABSTRACT FROM AUTHOR]

Aims: Physicians determine the treatment regimen for metastatic colorectal cancer on a case-by-case bases, according to the individual disease characteristics. We retrospectively compared the baseline characteristics and efficacies of first-line treatment among patients with metastatic colorectal cancer who received intensive therapy involving fluoropyrimidine plus oxaliplatin and/or irinotecan, potentially with molecularly targeted agents as well, versus less intensive fluoropyrimidine and/or bevacizumab therapy. Materials & methods: Data were collected from a medical claims database. The efficacy outcomes were: time to treatment failure, time to first subsequent therapy and overall survival. Results: The less intensive therapy group (n = 633) had higher median age, lower daily activity levels and shorter time to treatment failure, time to first subsequent therapy and overall survival than the intensive therapy group (n = 3829). Combination therapy with molecularly targeted agents and bevacizumab improved treatment efficacy outcomes in the intensive and less intensive groups, respectively. Conclusion: Patient age and daily activity levels were important factors for determining treatment intensity. In this study we performed a real-world data analysis of treatment for advanced colorectal cancer that had spread to other parts of patients' bodies, by investigating the medical records of 4462 patients. We wanted to see how well different treatments worked and what kinds of patients received them. We found that the most important factors when choosing between different treatments were the patient's age and how well they could perform their everyday tasks. We found that using specialized medicines in the intensive treatment group, and a drug called bevacizumab in the less intensive group, resulted in better patient outcomes. In real-world data on first-line treatment of patients with mCRC, age and daily activity levels were key in choosing intensive or less intensive therapy. Molecularly targeted agents improved outcomes with intensive therapy. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to investigate which treatment, neoadjuvant chemoradiotherapy (NAC‐RT) with S‐1 or combination neoadjuvant chemotherapy with gemcitabine and S‐1 (NAC‐GS), is more promising as neoadjuvant treatment (NAT) for resectable pancreatic cancer in terms of effectiveness and safety. Methods: In the NAC‐RT with S‐1 group, the patients received a total radiation dose of 50.4 Gy in 28 fractions with oral S‐1. In the NAC‐GS group, the patients received intravenous gemcitabine at a dose of 1000 mg/m2 with oral S‐1 for two cycles. The primary endpoint was the 2‐year progression‐free survival (PFS) rate. The trial was registered with the UMIN Clinical Trial Registry as UMIN000014894. Results: From April 2014 to April 2017, a total of 103 patients were enrolled. After exclusion of one patient because of ineligibility, 51 patients were included in the NAC‐RT with S‐1 group, and 51 patients were included in the NAC‐GS group in the intention‐to‐treat analysis. The 2‐year PFS rate was 45.0% (90% confidence interval [CI]: 33.3%–56.0%) in the NAC‐RT with S‐1 group and 54.9% (42.8%–65.5%) in the NAC‐GS group (p =.350). The 2‐year overall survival rate was 66.7% in the NAC‐RT with S‐1 group and 72.4% in the NAC‐GS group (p =.300). Although leukopenia and neutropenia rates were significantly higher in the NAC‐GS group than in the NAC‐RT with S‐1 group (p =.023 and p <.001), other adverse events of NAT and postoperative complications were comparable between the two groups. Conclusion: Both NAC‐RT with S‐1 and NAC‐GS are considered promising treatments for resectable pancreatic cancer. [ABSTRACT FROM AUTHOR]

In modern medicine, medical tests are used for various purposes including diagnosis, disease screening, prognosis, and risk prediction. To quantify the performance of the binary medical test, we often use sensitivity, specificity, and negative and positive predictive values as measures. Additionally, the F1$$ {F}_1 $$‐score, which is defined as the harmonic mean of precision (positive predictive value) and recall (sensitivity), has come to be used in the medical field due to its favorable characteristics. The F1$$ {F}_1 $$‐score has been extended for multi‐class classification, and two types of F1$$ {F}_1 $$‐scores have been proposed for multi‐class classification: a micro‐averaged F1$$ {F}_1 $$‐score and a macro‐averaged F1$$ {F}_1 $$‐score. The micro‐averaged F1$$ {F}_1 $$‐score pools per‐sample classifications across classes and then calculates the overall F1$$ {F}_1 $$‐score, whereas the macro‐averaged F1$$ {F}_1 $$‐score computes an arithmetic mean of the F1$$ {F}_1 $$‐scores for each class. Additionally, Sokolova and Lapalme1$$ {}^1 $$ gave an alternative definition of the macro‐averaged F1$$ {F}_1 $$‐score as the harmonic mean of the arithmetic means of the precision and recall over classes. Although some statistical methods of inference for binary and multi‐class F1$$ {F}_1 $$‐scores have been proposed, the methodology development of hypothesis testing procedure for them has not been fully progressing yet. Therefore, we aim to develop hypothesis testing procedure for comparing two F1$$ {F}_1 $$‐scores in paired study design based on the large sample multivariate central limit theorem. [ABSTRACT FROM AUTHOR]

Background: Transcatheter arterial embolization (TAE) has long been used for hemostasis of traumatic or postoperative hemorrhage and embolization of tumors. Previous retrospective studies of TAE for painful bone metastases showed 60%–80% pain reduction with a median time to response of 1–2 days. Compared with radiotherapy and bisphosphonates, time to response appeared earlier than that of radiotherapy or bone-modifying agents. However, few prospective studies have examined TAE for this indication. Here, we describe the protocol for a confirmatory study designed to clarify the efficacy and safety profile of TAE. Methods: This study will be a multicenter, single-arm confirmatory study (phase 2–3 design). Patients with painful bone metastases from any primary tumor are eligible for enrollment. TAE will be the main intervention. Following puncture of the femoral artery under local anesthesia and insertion of an angiographic sheath, angiography will confirm that the injected region includes tumor vasculature. Catheter position will be adjusted so that the embolization range does not include non-target tissues. Spherical embolic material will then be slowly injected into the artery to embolize it. The primary endpoint (efficacy) is the proportion of subjects with pain relief at 72 h after TAE and the secondary endpoint (safety) is the incidence of all NCI Common Terminology Criteria for Adverse Events version 5.0 Grade 4 adverse events and Grade ≥ 3 necrosis of the central nervous system. Discussion: If the primary and secondary endpoints are met, TAE can be a treatment choice for painful bone metastases. Trial registry number is UMIN-CTR ID: UMIN000040794. Trial registration: The study is ongoing, and patients are currently being enrolled. Enrollment started in March 2021. A total of 36 patients have participated as of Aug 2022. Protocol Version: Ver1.4, 13/07/2022. [ABSTRACT FROM AUTHOR]

The test treatment in confirmatory clinical trials is often assessed using multiple primary endpoints. We considered that trial efficacy is confirmed only when there is superiority of at least one endpoint and non-inferiority of the remaining endpoints. Some researchers proposed testing procedures for multiple primary endpoints that are continuous variables. However, there has not yet been discussion of the case in which a trial has multiple binary endpoints in the above framework. In this study, we consider a testing procedure for multiple primary endpoints that are binary, and evaluate the performance of the proposed method through simulations. [ABSTRACT FROM AUTHOR]

A 2-step approach, Fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE), has been proposed to predict advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to develop a novel 3-step approach for predicting advanced fibrosis. We enrolled 284 biopsy-confirmed NAFLD patients from two tertiary care centers and developed subgroups (n = 190), including 3.7% of patients with advanced fibrosis, assuming a primary care setting. In the 3-step approach, patients with intermediate-to-high FIB-4 in the first step underwent an enhanced liver fibrosis test or measurement of type IV collagen 7S domain as the second step, and VCTE was performed if the second step value was higher than the cutoff. In 284 cases, a tertiary care cohort with 36.3% advanced fibrosis, the 3-step approach showed significantly higher specificity and positive predictive value than the 2-step approach. In the subgroup with 3.7% advanced fibrosis, the 3-step approach significantly reduced the referral rate to specialists, the number of high-risk patients (i.e., liver biopsy candidates), and healthcare costs by 12.5% to 15.8%. The 3-step approach may improve the diagnostic performance to predict advanced fibrosis in NAFLD, which could lower rates of referrals to specialists, liver biopsies, and medical costs. [ABSTRACT FROM AUTHOR]

Clinical studies often collect longitudinal and time-to-event data for each subject. Joint modeling is a powerful methodology for evaluating the association between these data. The existing models, however, have not sufficiently addressed the problem of missing data, which are commonly encountered in longitudinal studies. In this paper, we introduce a novel joint model with shared random effects for incomplete longitudinal data and time-to-event data. Our proposed joint model consists of three submodels: a linear mixed model for the longitudinal data, a Cox proportional hazard model for the time-to-event data, and a Cox proportional hazard model for the time-to-dropout from the study. By simultaneously estimating the parameters included in these submodels, the biases of estimators are expected to decrease under two missing scenarios. We estimated the proposed model by Bayesian approach, and the performance of our method was evaluated through Monte Carlo simulation studies. [ABSTRACT FROM AUTHOR]

Transporting patients down stairs by carrying is associated with a particularly high fall risk for patients and the occurrence of back pain among emergency medical technicians. The present study aimed to verify the effectiveness of the Airstretcher device, which was developed to reduce rescuers' physical burden when transporting patients by dragging along the floor and down stairs. Forty-one paramedical students used three devices to transport a 65-kg manikin down stairs from the 3rd to the 1st floor. To verify the physical burden while carrying the stretchers, ratings of perceived exertion were measured using the Borg CR10 scale immediately after the task. Mean Borg CR10 scores (standard deviation) were 3.6 (1.7), 4.1 (1.8), 5.6 (2.4), and 4.2 (1.8) for the Airstretcher with dragging, Airstretcher with lifting, backboard with lifting, and tarpaulin with lifting conditions, respectively (p < 0.01). Multiple comparisons revealed that the Airstretcher with dragging condition was associated with significantly lower Borg CR10 scores compared with the backboard with lifting condition (p < 0.01). When the analysis was divided by handling position, estimated Borg CR10 values (standard error) for head position were 4.4 (1.3), 2.9 (0.9), 3.2 (0.8), and 4.0 (1.1) for the Airstretcher with dragging, Airstretcher with lifting, backboard with lifting, and tarpaulin with lifting conditions, respectively, after adjusting for participant and duration time (F = 1.4, p < 0.25). The estimated Borg CR10 value (standard error) for toe position in the Airstretcher with dragging condition was 2.0 (0.8), and the scores for the side position were 4.9 (0.4), 6.1 (0.3), and 4.7 (0.4) for the Airstretcher with lifting, backboard with lifting, and tarpaulin with lifting conditions, respectively, after adjusting for participant and duration time (F = 3.6, p = 0.02). Transferring a patient down stairs inside a house by dragging using the Airstretcher may reduce the physical burden for rescuers. [ABSTRACT FROM AUTHOR]

In square contingency table analysis, we consider a partial measure that represents the degree of departure from symmetry for each of several pairs. It may be useful to pool the values of the measure into a single summary measure of partial asymmetry. We show that the estimator of partial measures is asymptotically mutually independent for a large sample size. The present paper proposes a symmetry measure in the class of weighted averages that is different from previous studies. The proposed measure is an approximation of the measure in the class of weighted averages that has the smallest variance. [ABSTRACT FROM AUTHOR]

Objectives: For suspected common bile duct stone (CBDS) missed on computed tomography (CT), there is no clear evidence on whether endoscopic ultrasound (EUS) or magnetic resonance cholangiopancreatography (MRCP) is the better diagnostic tool. We aimed to compare the diagnostic accuracy of EUS and MRCP for cases of missed CBDS on CT. Methods: Patients suspected of having CBDS were enrolled and randomly allocated to the EUS or MRCP group. Upon the initial examination, those having CBDS or sludge formation underwent endoscopic retrograde cholangiopancreatography (ERCP), while those who were CBDS‐negative underwent a second examination with either MRCP or EUS, which was distinct from the initial diagnostic procedure. The primary outcome was diagnostic accuracy, and the secondary outcomes were diagnostic ability, detection rate and characteristics of CBDS in the second examination, and the frequency of adverse events. Results: Between April 2019 and January 2021, 50 patients were enrolled in the study. The accuracy was 92.3% for EUS and 68.4% for MRCP (P = 0.055). EUS showed 100% sensitivity, 88.2% specificity, 81.8% positive predictive value, and 100% negative predictive value, and MRCP showed 33.3% sensitivity, 84.6% specificity, 50% positive predictive value, and 73.3% negative predictive value. The CBDS detection rate in the second examination was 0% for MRCP after a negative EUS and 35.7% for EUS after a negative MRCP (P = 0.041). No adverse events occurred in any of the patients. Conclusions: Endoscopic ultrasound may be a superior diagnostic tool compared to MRCP for the detection of CBDS that are undetected on CT. (UMIN000036357). [ABSTRACT FROM AUTHOR]

Background: The development of chemotherapy and treatment strategies for metastatic colorectal cancer (mCRC) have provided patients with significant survival benefits. Currently, molecular targeting agents and late‐line treatment with regorafenib and trifluridine/tipiracil (FTD/TPI) are available. However, the impact of this increase in drug availability on overall survival (OS) in mCRC remains a clinical question. Methods: We retrospectively collected data on consecutive mCRC patients who were treated at three institutions in Japan. We divided the patients into three cohorts: patients who initiated first‐line treatment from Jan 2005 to Dec 2006 (cohort A: only cytotoxic drugs available), Jan 2007 to Dec 2011 (cohort B: molecular targeting drugs available), and Jan 2012 to Sep 2016 (cohort C: late‐line treatment available). Results: A total of 1409 consecutive patients were analyzed. The median survival time (MST) in cohorts A, B, and C was 18.6, 25.4, and 26.4 months, respectively. The hazard ratio (HR) for cohort B versus A was 0.81 (95% CI 0.68–0.97), for cohort C versus A was 0.74 (95% CI 0.61–0.89), and for cohort C versus B was 0.92 (0.81–1.03). The median number of administered drugs (range) was 3 (1–5) in cohort A, 4 (1–7) in cohort B, and 4 (1–7) in cohort C. The increase in drug availability extended the MST from 15.5 months in patients treated with ≤3 drugs to 36.0–37.3 months in patients treated with six to seven drugs. Conclusion: The development of chemotherapy including late‐line treatments could improve the prognosis of mCRC patients. [ABSTRACT FROM AUTHOR]

A binary classification problem is common in medical field, and we often use sensitivity, specificity, accuracy, negative and positive predictive values as measures of performance of a binary predictor. In computer science, a classifier is usually evaluated with precision (positive predictive value) and recall (sensitivity). As a single summary measure of a classifier's performance, F1 score, defined as the harmonic mean of precision and recall, is widely used in the context of information retrieval and information extraction evaluation since it possesses favorable characteristics, especially when the prevalence is low. Some statistical methods for inference have been developed for the F1 score in binary classification problems; however, they have not been extended to the problem of multi-class classification. There are three types of F1 scores, and statistical properties of these F1 scores have hardly ever been discussed. We propose methods based on the large sample multivariate central limit theorem for estimating F1 scores with confidence intervals. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits varying degrees of protective immunity conferred by neutralizing antibodies (nAbs). In this study, we report the persistence of nAb responses over 12 months after infection despite their decreasing trend noticed from 6 months. Methods The study included sera from 497 individuals who had been infected with SARS-CoV-2 between January and August 2020. Samples were collected at 6 and 12 months after onset. The titers of immunoglobulin (Ig)G to the viral nucleocapsid protein (NP) and receptor-binding domain (RBD) of the spike protein were measured by chemiluminescence enzyme immunoassay. The nAb titer was determined using lentivirus-based pseudovirus or authentic virus. Results Antibody titers of NP-IgG, RBD-IgG, and nAbs were higher in severe and moderate cases than in mild cases at 12 months after onset. Although the nAb levels were likely to confer adequate protection against wild-type viral infection, the neutralization activity to recently circulating variants in some of the mild cases (~30%) was undermined, implying the susceptibility to reinfection with the variants of concerns (VOCs). Conclusions Coronavirus disease 2019 convalescent individuals have robust humoral immunity even at 12 months after infection albeit that the medical history and background of patients could affect the function and dynamics of antibody response to the VOCs. [ABSTRACT FROM AUTHOR]

Background: Although childhood undervaccination among single mother families is a concern for child healthcare, their association is still under debate. This study aimed to investigate the association between maternal marital status and the risk of childhood undervaccination and determine the mediating effect of household income.Methods: We utilised prospective birth cohort from the Japan Environment and Children's Study (JECS). Of 104,062 foetal records (children) from 97,413 mothers, 82,462 that included mothers recruited between 2011 and 2014, were analysed. Childhood undervaccination was defined as not having been vaccinated with at least one routine vaccine. A log-binomial regression analysis was used to estimate the risk ratio (RR) for the association between maternal marital status and the risk of childhood undervaccination. A causal mediation analysis was further performed to investigate the proportion of the association mediated by household income.Results: Among 82,462 children, 3188 and 79,274 had unmarried and married mothers, respectively. Childhood undervaccination was observed in 1053 (33.0%) and 16,901 (21.3%) children of unmarried and married mothers, respectively. Maternal marital status was associated with a higher risk of childhood undervaccination (adjusted risk ratio [aRR], 1.34; 95% confidence interval [CI], 1.27 to 1.41). Compared with married and older mothers, both unmarried and older (aRR, 1.54; 95% CI, 1.35 to 1.77) and unmarried and younger (aRR, 1.66; 95% CI, 1.54 to 1.79) mothers were associated with a higher risk of childhood undervaccination. The causal mediation analysis showed that the proportion mediated by household income was 10.5% (95% CI, 9.9 to 11.0%).Conclusions: This nationwide, prospective, large-scale birth cohort study found that a household with a single mother was associated with an increased risk of childhood undervaccination, and 10% of this association was explained by household income. These findings underscore the importance of improving the social environment among single mother families, including not only poverty but also working conditions. [ABSTRACT FROM AUTHOR]

Aims: There is a paucity of comparative data on the use of sorafenib and lenvatinib for unresectable hepatocellular carcinoma. We assessed the real‐world treatment outcomes between using sorafenib and lenvatinib for unresectable hepatocellular carcinoma in the multiple molecular‐targeted therapy era. Methods and Results: We enrolled 386 patients treated with sorafenib or lenvatinib as the first‐line therapy for unresectable hepatocellular carcinoma at multiple centers. Propensity score matching was performed to adjust for differences in baseline and tumor characteristics between the two groups. Propensity score matching identified 110 patients in each treatment group. The median overall survival was similar between lenvatinib and sorafenib (14.8 and 13.0 months, respectively; P = 0.352). The median progression‐free survival was longer with lenvatinib than with sorafenib (7.6 and 3.9 months, respectively; P < 0.001). The overall response rate (P < 0.001) and disease control rate (P = 0.015), as defined by the modified Response Evaluation Criteria in Solid Tumors, were significantly better with lenvatinib than with sorafenib. The median overall survival was longer in patients who received subsequent treatment than in those who did not in the sorafenib group (23.1 and 5.7 months, respectively; P < 0.001), whereas the median overall survival with or without subsequent treatment did not differ significantly in the lenvatinib group (17.8 and 14.7 months, respectively; P = 0.439). Conclusion: Overall survival with sorafenib and lenvatinib was not significantly different. However, patients who received subsequent treatments had longer overall survival than those who received only first‐line treatment with sorafenib, whereas lenvatinib did not show this effect. [ABSTRACT FROM AUTHOR]

For square contingency tables with ordered categories, the marginal homogeneity model is represented by various expressions, and some extensions of the marginal homogeneity model were proposed. Herein we consider the marginal continuation-ratio to examine a new expression of the marginal homogeneity model. We also propose an extension of the marginal homogeneity model using the ratio of marginal continuation-ratios; namely, the marginal continuation odds ratio. The proposed model can be interpreted in various ways. Additionally, we propose a generalization of it, and decompose the marginal homogeneity model using the generalized model. Furthermore, we extend the models and decompositions into multi-way contingency tables. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic is an unprecedented threat to humanity that has provoked global health concerns. Since the etiopathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. Accurately predicting the progression of the disease would aid in appropriate patient categorization and thus help determine the best treatment option. Here, we have introduced a proteomic approach utilizing data-independent acquisition mass spectrometry (DIA-MS) to identify the serum proteins that are closely associated with COVID-19 prognosis. Twenty-seven proteins were differentially expressed between severely ill COVID-19 patients with an adverse or favorable prognosis. Ingenuity Pathway Analysis revealed that 15 of the 27 proteins might be regulated by cytokine signaling relevant to interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF), and their differential expression was implicated in the systemic inflammatory response and in cardiovascular disorders. We further evaluated practical predictors of the clinical prognosis of severe COVID-19 patients. Subsequent ELISA assays revealed that CHI3L1 and IGFALS may serve as highly sensitive prognostic markers. Our findings can help formulate a diagnostic approach for accurately identifying COVID-19 patients with severe disease and for providing appropriate treatment based on their predicted prognosis. [ABSTRACT FROM AUTHOR]

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Background: Naples prognostic score (NPS) is a scoring system based on albumin, cholesterol concentration, lymphocyte-to-monocyte ratio, and neutrophil-to-lymphocyte ratio reflecting host systemic inflammation, malnutrition, and survival for several malignancies. This study was designed to assess the prognostic significance of NPS in patients with locally advanced esophageal squamous cell carcinoma (ESCC) and to compare its prognostic accuracy with that of other systemic inflammatory and nutritional index. Methods: We retrospectively examined 165 patients with locally advanced ESCC who underwent neoadjuvant therapy followed by curative resection between January 2011 and September 2019. Patients were divided into three groups based on their NPS before neoadjuvant therapy (Group 0: NPS = 0; Group 1: NPS = 1–2; Group 2: NPS = 3–4). We compared the clinicopathological characteristics and survival rates among the groups. Results: The 5-year recurrence-free survival (RFS) and overall survival (OS) rates were significantly different between the groups (P < 0.001). The NPS was superior to other systemic inflammatory and nutritional index for predicting prognoses, as determined using area under the curves (P < 0.05). Multivariate analysis demonstrated that the NPS was a significant predictor of poor RFS (Group 1: hazard ratio [HR] 1.897, P = 0.049; Group 2: HR 3.979, P < 0.001) and OS (Group 1: HR 2.152, P = 0.033; Group 2: HR 3.239, P = 0.006). Conclusions: The present study demonstrated that NPS was an independent prognostic factor in patients with locally advanced ESCC and more reliable and accurate than the other systemic inflammatory and nutritional index. [ABSTRACT FROM AUTHOR]

In clinical research, collected data are often classified into ordered categories using a set threshold to evaluate efficacy and safety of treatment. Data can be summarized as a shift table, which displays the change in the frequency of subjects across specified categories from the baseline to post-baseline. Although ordered categories are sometimes recombined into three categories, the combined patterns vary. To consider various collapsed patterns comprehensively, this paper proposes a new measure that represents the degree of departure from average marginal homogeneity, and can distinguish between two kinds of marginal inhomogeneity. Additionally, applications of the proposed measure to clinical data are discussed. [ABSTRACT FROM AUTHOR]

Background: The lymph node (LN) ratio (LNR) and the log odds of positive LNs (LODDS) have been proposed as sensitive prognosticators in patients with primary gastric cancer, especially in patients with an insufficient number of harvested LNs. We investigated the association of LNR and LODDS with survival in patients with remnant gastric cancer (RGC) and explored whether these staging methods are prognostic factors in patients with an insufficient number of harvested LNs. Methods: The present study retrospectively examined 95 patients with RGC who received gastrectomy between January 2000 and December 2018. The patients were classified according to the adjusted X-tile cutoff for LNR and LODDS. The association between survival rates and clinicopathological features was investigated. The predictive accuracy of the LNR and LODDS was compared with that of the Union for International Cancer Control pathological N factor. Results: Multivariate analysis revealed that the LNR and LODDS were independent risk factors for recurrence-free survival (RFS) [hazard ratio (HR) 2.623, p = 0.020; HR 3.404, p = 0.004, respectively] and overall survival (OS) (HR 3.694, p = 0.003; HR 2.895, p = 0.022, respectively) in patients with RGC. Moreover, even in patients with 15 or fewer harvested LNs, only the LNR was a significant independent risk factor for RFS (HR 21.890, p < 0.001) and OS (HR 6.597, p = 0.002). The receiver operating characteristic curves revealed that the prognostic accuracy of the three methods was comparable (p > 0.05). Conclusion: LNR has significant prognostic value for patients with RGC, including those with an insufficient number of harvested LNs. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux may exacerbate chronic lung disease in preterm infants. We evaluated the short-term effects of transpyloric feeding on respiratory status in preterm infants during mechanical ventilation. We retrospectively collected data from the hospital information management system. To evaluate the effect of transpyloric feeding on oxygenation, we compared changes in SpO2/FiO2 ratios before and after commencing transpyloric feeding by a piecewise linear regression model. We examined 33 infants (median gestational age, 25.4 weeks; median birth weight, 656 g) who underwent transpyloric feeding. All tubes were placed at the bedside without fluoroscopy. No cases of unsuccessful placement, gastroduodenal perforation, or tracheal misinsertion occurred. Transpyloric feeding began at a median age of 18 (interquartile range, 15–23) days. Mean SpO2/FiO2 (±SD) ratios were 391 (±49), 371 (±51), 365 (±56), and 366 (±53) 72–96 h before, 0–24 h before, 48–72 h after, and 96–120 h after starting transpyloric feeding, respectively. The rate of change per hour of SpO2/FiO2 ratios increased 48–120 h after compared with 0–96 h before transpyloric feeding (0.03 [95% confidence interval, −0.10 to 0.17] vs. −0.29 [−0.47 to −0.12]) (p=0.007). No apparent changes occurred in the mean airway pressure, amplitude pressure, or pCO2. Transpyloric feeding during mechanical ventilation can prevent the deterioration of oxygenation without major complications at the stage of respiratory exacerbation in preterm infants. [ABSTRACT FROM AUTHOR]

Background: Anti‐programmed death‐1 (PD‐1) immunotherapy can cause immune‐related pneumonitis, also known as checkpoint inhibitor pneumonitis (CIP). CIP that develops early after the initiation of anti‐PD‐1 immunotherapy is important because it is more severe than CIP that develops later. However, only a few studies have examined the risk factors for early‐onset CIP. Previous studies have reported several risk factors for CIP, including imaging findings of airway obstruction adjacent to lung tumors. However, the utility of this factor is debatable. Therefore, we investigated potential risk factors for early‐onset CIP, including tumor invasion in the central airway (TICA), in patients with non‐small cell lung cancer (NSCLC) receiving anti‐PD‐1 therapy. Methods: We retrospectively analyzed the medical records and chest computed tomography scans of patients with NSCLC treated with anti‐PD‐1 antibodies at the Kanagawa Cancer Center in Japan between 1 January 2016, and 30 June 2018. The clinical characteristics and imaging findings, including TICA, were compared between patients with and without early‐onset CIP. Results: Data from 181 eligible patients (114 receiving nivolumab and 67 receiving pembrolizumab) were analyzed. Early‐onset CIP occurred in 13 of 79 patients (16.5%) with TICA and 2 of 102 patients (2.0%) without TICA. In multivariate analysis, the odds ratio of early‐onset CIP for patients with TICA was 8.2 (95% confidence interval [CI]: 1.98–34.0, P = 0.0037). Conclusions: TICA was strongly associated with early‐onset CIP in patients with NSCLC. Clinicians should carefully observe patients with TICA, especially within three months of anti‐PD‐1 antibody administration because of high CIP risk. Key points: Significant study findings: Tumor invasion in the central airway (TICA) was a predictor of early‐onset checkpoint inhibitor pneumonitis (CIP)TICA had good interobserver variability, indicating its utility in clinical practicePatients with TICA might have a higher immune status than patients without What this study adds: This is the first study focusing on risk factors for CIP limited to early‐onset CIP. [ABSTRACT FROM AUTHOR]

Background: Lymph node ratio (LNR), defined as the ratio of metastatic nodes to the total number of examined lymph nodes, has been proposed as a sensitive prognostic factor in patients with gastric cancer (GC). We investigate its association with survival in pathological stage (pStage) II/III GC and explore whether this is a prognostic factor in each Union for International Cancer Control pStage (7th edition). Patients and Methods: We retrospectively examined 838 patients with pStage II/III GC who underwent curative gastrectomy between June 2000 and December 2018. Patients were classified into low-LNR (L-LNR), middle-LNR (M-LNR), and high-LNR (H-LNR) groups according to adjusted X-tile cutoff values of 0.1 and 0.25 for LNR, and their clinicopathological characteristics and survival rates were compared. Results: The 5-year recurrence-free survival (RFS) and overall survival (OS) rates postsurgery showed significant differences among the groups (P < 0.001). Multivariate analysis demonstrated that LNR was a significant predictor of poor RFS [M-LNR: hazard ratio (HR) 3.128, 95% confidence interval (CI) 2.254–4.342, P < 0.001; H-LNR: HR 5.148, 95% CI 3.546–7.474, P < 0.001] and OS (M-LNR: HR 2.749, 95% CI 2.038–3.708, P < 0.001; H-LNR: HR 4.654, 95% CI 3.288–6.588, P < 0.001). On subset analysis stratified by pStage, significant differences were observed between the groups in terms of the RFS curves of pStage II and III GC (P < 0.001 and < 0.001, respectively) and OS curves of pStage II and III GC (P = 0.001 and < 0.001, respectively). Conclusions: High LNR is a predictor of worse prognosis in pStage II/III GC, including each substage. [ABSTRACT FROM AUTHOR]

Aim: Bile salt export pump (BSEP) deficiency manifests a form of progressive intrahepatic cholestasis. This study aimed to establish a scoring system of liver histology for the uncommon genetic condition. Methods: After a roundtable discussion and histology review, a scoring system for BSEP deficiency was established. Eleven tissue samples were independently evaluated by three pathologists based on the proposed standard for an interobserver agreement analysis. In four cases with serial tissue samples available, correlation between changes in histology scores and clinical outcome was examined. Results: Of 14 initially listed histopathological findings, 12 were selected for scoring and grouped into the following four categories: cholestasis, parenchymal changes, portal tract changes and fibrosis. Each category consisted of two to four microscopic findings that were further divided into three to six scores; therefore, each category had a maximum score of 8–11. Interobserver agreement was highest for pericellular fibrosis (κ = 0.849) and lowest for hepatocellular cholestasis (κ = 0.241) with the mean and median κ values of the 12 parameters being 0.561 and 0.602, respectively. For two patients whose clinical features worsened, score changes between two time points were interpreted as deteriorated. In two patients, who showed a good clinical response to preprandial treatment with sodium 4‐phenylbutyrate, histological changes were evaluated as improved or unchanged. Conclusions: The proposed histology‐based scoring system for BSEP deficiency with moderate interobserver agreement may be useful not only for monitoring microscopic changes in clinical practice but also for a surrogate endpoint in clinical trials. [ABSTRACT FROM AUTHOR]

In clinical researches, various clinical scales with ordered categories are used to evaluate the efficacy and safety/toxicity of treatments. Such the clinical scales are sometimes summarized on the transition between the baseline and the study end point as a square contingency table. Also, clinical scales may be reclassified into three groups. However, the cutpoints can be varied depending on clinical researches or clinicians. Hence, this paper proposes a measure which is expressed by using same weights for collapsed tables and which can see the directionality for two kinds of asymmetries. Also, this paper shows an application of the proposed measure to clinical data, and that the proposed measure is a useful statistical method for analyzing ordered categorical data. [ABSTRACT FROM AUTHOR]

Background: We developed a novel high-sensitive assay for plasma xanthine oxidoreductase (XOR) activity that is not affected by the original serum uric acid level. However, the association of plasma XOR activity with that level has not been fully examined. Methods: This cross-sectional study included 191 subjects (91 males, 100 females) registered in the MedCity21 health examination registry. Plasma XOR activity was determined using our assay for plasma XOR activity with [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. Serum levels of uric acid and adiponectin, and visceral fat area (VFA) obtained by computed tomography were measured, and insulin resistance was determined based on the homeostasis model assessment (HOMA-IR) index. Results: The median values for uric acid and plasma XOR activity were 333 μmol/L and 26.1 pmol/h/mL, respectively. Multivariable linear regression analysis showed a significant and positive association of serum uric acid level (coefficient: 26.503; 95% confidence interval: 2.06, 50.945; p = 0.035) with plasma XOR activity independent of VFA and HOMA-IR, and also age, gender, alcohol drinking habit, systolic blood pressure, estimated glomerular filtration rate (eGFR), glycated hemoglobin A1c, triglyceride, and adiponectin levels. The "gender*XOR activity" interaction was not significant (p = 0.91), providing no evidence that gender modifies the relationship between plasma XOR activity and serum uric acid level. Conclusions: Plasma XOR activity was found to be positively associated with serum uric acid level independent of other known confounding factors affecting that level, including gender difference, eGFR, adiponectin level, VFA, and HOMA-IR. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the association of tumor size with patient survival following diagnosis of solitary hepatocellular carcinoma without vascular invasion.Methods: The overall population comprised 638 patients who initially underwent hepatic resection with curative intent for a solitary hepatocellular carcinoma without macroscopic vascular invasion (487 had no microscopic vascular invasion). We set 5 cm as the tumor cutoff size for a solitary tumor based on the Milan criteria, and we used a multivariate Cox proportional hazards model and propensity score matching to evaluate the impact of tumor size on survival.Results: Tumor size was significantly associated with a proportional increase in cancer-specific survival in the overall population (P = 0.001) and the subgroup with no microscopic vascular invasion (P = 0.029); however, multivariate analysis revealed no significant risk associated with recurrence-free survival (P = 0.055 and 0.59, respectively). After propensity score matching, the cancer-specific survival of patients with tumors > 5 cm was significantly worse than for those with tumors ≤ 5 cm in the overall population (P = 0.0077); the corresponding 2-year cumulative recurrence rates were 45.8% and 23.5%, respectively (P = 0.0027). Finally, the proportions of extrahepatic to total recurrences were 8% for those with tumors ≤ 5 cm and 29.1% for those with tumors > 5 cm in the unmatched overall population (P < 0.001).Conclusion: Tumor size was associated with recurrence within 2 years of surgery and with poor cancer-specific survival in patients with solitary hepatocellular carcinoma, even in the absence of microscopic vascular invasion. [ABSTRACT FROM AUTHOR]

Positive and negative predictive values describe the clinical performance of the diagnostic test when it is applied to a cohort of individuals. Testing non-inferiority of predictive values may be adequate in some cases due to the simplicity of the examination and the invasiveness of the test, but no non-inferiority test for predictive values has been proposed yet. In this study, we propose a non-inferiority test that investigates the non-inferiority of predictive values in paired designs, and formulae for the calculation of sample size to execute the non-inferiority test of two predictive values. Simulation studies showed that the proposed non-inferiority test is useful for comparing two predictive values in clinical trials. [ABSTRACT FROM AUTHOR]

Positive and negative predictive values describe the performance of a diagnostic test. There are several methods to test the equality of predictive values in paired designs. However, these methods were premised on large sample theory, and they may not be suitable for small‐size clinical trials because of inflation of the type 1 error rate. In this study, we propose an exact test to control the type 1 error rate strictly for conducting a small‐size clinical trial that investigates the equality of predictive values in paired designs. In addition, we execute simulation studies to evaluate the performance of the proposed exact test and existing methods in small‐size clinical trials. The proposed test can calculate the exact P value, and as a result of simulations, the empirical type 1 error rate for the proposed test did not exceed the significance level regardless of the setting, and the empirical power for the proposed test is not much different from the other methods based on large‐sample theory. Therefore, it is considered that the proposed exact test is useful when the type 1 error rate needs to be controlled strictly. [ABSTRACT FROM AUTHOR]

Background. Higher levels of uric acid production have been reported in individuals with visceral fat obesity, and obesity is known to enhance xanthine oxidoreductase (XOR) activity, although the precise mechanism remains unclear. We investigated the associations of visceral fat area (VFA), serum adiponectin level, and insulin resistance with plasma XOR activity using our novel highly sensitive assay based on [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. Methods. This cross-sectional study included 193 subjects (92 males and 101 females) registered in the MedCity21 health examination registry. Plasma XOR activity, serum adiponectin level, and VFA obtained by computed tomography were measured, and insulin resistance was determined based on the homeostasis model assessment (HOMA-IR) index. Results. The mean values for VFA, log HOMA-IR, and log plasma XOR activity were 76.8 ± 45.8 cm2, 0.14 ± 0.30, and 1.50 ± 0.44 pmol/h/mL, respectively. Multiple regression analysis showed that HOMA-IR was significantly (p = 0.020) associated with plasma XOR activity independent of other factors, including VFA and adiponectin level, as well as age, sex, alcohol drinking habit, smoking habit, alanine transaminase, HbA1c, and eGFR. The " sex∗HOMA − IR " interaction was not significant (p = 0.89), indicating that sex difference does not have an effect on the relationship between HOMA-IR and plasma XOR activity. Conclusions. Our results indicate that insulin resistance is associated with plasma XOR activity and that relationship is independent of visceral adiposity and adiponectin level, suggesting that the development of insulin resistance resulting from increased visceral adiposity and/or reduced serum adiponectin contributes to increased uric acid production by stimulating XOR activity. [ABSTRACT FROM AUTHOR]

Aim: To investigate the frequency and risk factors of perioperative, symptomatic venous thromboembolism (VTE) after gastroenterological surgery. Methods: We assessed the frequency of and risk factors for VTE after eight gastroenterological procedures (total 516 217 cases including, gastrectomy, total gastrectomy, hepatectomy, esophagectomy, right hemicolectomy, low anterior resection, pancreaticoduodenectomy, and acute pan‐peritonitis surgery) based on data from the National Clinical Database. Data collected between 2011 and 2013 (382 124 cases) were used as a test set, and data from 2014 (134 093 cases) were used as a validation set. Results: The frequency of deep vein thrombosis (DVT) was 0.3% (382 124 cases), and the incidence of pulmonary embolism (PE) was 0.2% (382 124 cases) ranging from 0.1% to 0.7% for DVT and from 0.1% and 0.3% for PE among eight surgeries, respectively. Analyses using pre‐and intra‐operative factors identified the top three risk factors for VTE as esophagectomy, pancreaticoduodenectomy, and hepatectomy. Using pre‐, intra‐, and postoperative factors, the second through fourth risk factors were sepsis, prolonged ventilation >48 hours and readmission within 30 days. The highest risks factor for PE using pre‐, intra‐, and postoperative factors were any cardiac events. Unplanned intubation was the fourth risk factor. Conclusion: The risk for DVT and PE differed for each surgical procedure. VTE and PE risk factors changed after considering postoperative factors. It may be necessary to reconsider the prophylaxis depending on whether the complication occurs after surgery, particularly breathing and cardiac complications. [ABSTRACT FROM AUTHOR]

Background: The Mayo Clinic Image Classification (MIC) was proposed as a renal prognosis prediction model for autosomal dominant polycystic kidney disease (ADPKD). MIC is based on the assumption of exponential constant increase in height-adjusted total kidney volume (HtTKV). HtTKV growth rate is calculated by one-time measurement of HtTKV and age. We named it as an age-adjusted HtTKV growth rate (AHTKV-α). AHTKV-α was compared with HtTKV slope measured by at least two HtTKV values.Methods: Comparison of repeatability between AHTKV-α and HtTKV slope, correlation of subgroups divided according to baseline AHTKV-α and HtTKV slope with disease manifestations, estimated glomerular filtration rate (eGFR) slope, and renal survival were analyzed in 296 patients with ADPKD. PKD genotype influences were compared between AHTKV-α and HtTKV slope in 88 patients with characterized PKD mutations.Results: Absolute differences between baseline and follow-up measures were significantly larger for the HtTKV slope than for AHTKV-α (P < 0.0001). From baseline AHTKV-α-based subgroups A-E according to MIC, disease manifestations occurred earlier and future eGFR slopes became steeper (P < 0.0001). Multivariate hazard ratios of renal survival differed significantly among baseline AHTKV-α-based subgroups. Inter-subgroup differences in these predictors were less evident during baseline HtTKV slope-based classification. AHTKV-α values, but not HtTKV slopes, were significantly higher for PKD1 mutation carriers than for PKD2 mutation carriers (P < 0.0001).Conclusion: MIC is a good renal prediction model applicable to Japanese patients also. AHTKV-α can be a more sensitive and reliable indicator in TKV growth rate than HtTKV slope. [ABSTRACT FROM AUTHOR]

Background and Aim: Esophageal endoscopic submucosal dissection (ESD) to resect widespread lesions has increased the incidence of strictures, and some patients develop strictures despite receiving prophylactic locoregional triamcinolone injections. The present study evaluated the predictive factors for esophageal stricture formation in patients given prophylactic triamcinolone injections after ESD. Methods: This was a retrospective observational study. Of 552 consecutive patients who underwent ESD, those who received prophylactic triamcinolone injections immediately after ESD were enrolled. Primary outcome was predictive factors for esophageal stricture formation in patients given prophylactic triamcinolone injections. Results: We evaluated 101 en bloc resections involving 144 lesions in 96 patients. Strictures occurred following 17 (16.8%) resections. Wider circumferential mucosal defect (odds ratio [OR] 2.42, 95% confidence interval [CI]: 1.01–5.80; P = 0.048) was an independent predictive factor for stricture development. Cut‐off value associated with stricture formation was five‐sixths of the circumferential mucosal defect. Propensity analysis determined that frequency of esophageal strictures increased in patients with circumferential mucosal defects of more than five‐sixths compared with those less than five‐sixths (OR = 5.70, 95% CI: 1.61–20.18; P = 0.007). Conclusion: Resections involving circumferential mucosal defects of more than five‐sixths increased the likelihood of stricture formation in patients given prophylactic locoregional triamcinolone injections after esophageal ESD. [ABSTRACT FROM AUTHOR]

Objectives: In the brain, the mechanisms of attention to the left and the right are known to be different. It is possible that brain activity when driving also differs with different horizontal road alignments (left or right curves), but little is known about this. We found driver brain activity to be different when driving on left and right curves, in an experiment using a large-scale driving simulator and functional near-infrared spectroscopy (fNIRS). Research Design and Methods: The participants were fifteen healthy adults. We created a course simulating an expressway, comprising straight line driving and gentle left and right curves, and monitored the participants under driving conditions, in which they drove at a constant speed of 100 km/h, and under non-driving conditions, in which they simply watched the screen (visual task). Changes in hemoglobin concentrations were monitored at 48 channels including the prefrontal cortex, the premotor cortex, the primary motor cortex and the parietal cortex. From orthogonal vectors of changes in deoxyhemoglobin and changes in oxyhemoglobin, we calculated changes in cerebral oxygen exchange, reflecting neural activity, and statistically compared the resulting values from the right and left curve sections. Results: Under driving conditions, there were no sites where cerebral oxygen exchange increased significantly more during right curves than during left curves (p > 0.05), but cerebral oxygen exchange increased significantly more during left curves (p < 0.05) in the right premotor cortex, the right frontal eye field and the bilateral prefrontal cortex. Under non-driving conditions, increases were significantly greater during left curves (p < 0.05) only in the right frontal eye field. Conclusions: Left curve driving was thus found to require more brain activity at multiple sites, suggesting that left curve driving may require more visual attention than right curve driving. The right frontal eye field was activated under both driving and non-driving conditions. [ABSTRACT FROM AUTHOR]

For square contingency tables with ordered categories, there may be some cases that one wants to analyze them by considering collapsed tables with some adjacent categories combined in the original table. This paper considers the symmetry model for collapsed square contingency tables and proposes a measure to represent the degree of departure from symmetry. The proposed measure is defined as the arithmetic mean of submeasures each of which represents the degree of departure from symmetry for each collapsed 3×3 table. Each submeasure also represents the mean of power-divergence or diversity index for each collapsed table. Examples are given. [ABSTRACT FROM AUTHOR]