Osamu KOMORI

Abstract Purpose The overall goal of our study is to create modified Alberta Stroke Program Early Computed Tomography Score (ASPECTS) determined by the findings on arterial spin labeling imaging (ASL) to predict the prognosis of patients with acute ischemic stroke after successful mechanical thrombectomy (MT). Prior to that, we examined predictive factors including the value of cerebral blood flow (CBF) measured by ASL for occurrence of cerebral infarction at the region of interest (ROI) used in the ASPECTS after successful MT. Methods Of the 92 consecutive patients with acute ischemic stroke treated with MT at our institution between April 2013 and April 2021, a total of 26 patients who arrived within 8 h after stroke onset and underwent MT resulting in a thrombolysis in cerebral infarction score of 2B or 3 were analyzed. Magnetic resonance imaging, including diffusion-weighted imaging (DWI) and ASL, was performed on arrival and the day after MT. The asymmetry index (AI) of CBF by ASL (ASL-CBF) before MT was calculated for 11 regions of interest using the DWI-Alberta Stroke Program Early CT Score. Results Occurrence of infarction after successful MT for ischemic stroke in the anterior circulation can be expected when the formula 0.3211 × history of atrial fibrillation +0.0096 × the AI of ASL-CBF before MT (%) +0.0012 × the time from onset to reperfusion (min) yields a value below 1.0 or when the AI of ASL-CBF before MT is below 61.5%. Conclusion The AI of ASL-CBF before MT or a combination of a history of atrial fibrillation, the AI of ASL-CBF before MT, and the time from onset to reperfusion can be used to predict the occurrence of infarction in patients arriving within 8 h after stroke onset in which reperfusion with MT was successful.

BACKGROUND: The role of visual evoked potential (VEP) in direct clipping of the paraclinoid internal carotid artery (ICA) aneurysm remains uncertain. OBJECTIVE: To examine whether intraoperative neuromonitoring with VEP can predict deterioration of visual function after direct clipping of the paraclinoid ICA aneurysm with anterior clinoidectomy. METHODS: Among consecutive 274 patients with unruptured cerebral aneurysm, we enrolled 25 patients with paraclinoid ICA aneurysm treated by direct clipping after anterior clinoidectomy with intraoperative neuromonitoring with VEP in this study. We evaluated the visual acuity loss (VAL) and visual field loss (VFL) before surgery, 1 month after surgery, and at the final follow-up. RESULTS: The VAL at 1 month after surgery (VAL1M) and VAL at the final follow-up (Final VAL) were significantly related to the reduction rate of VEP amplitude at the end of surgery (RedEnd%), more than 76.5%, and the maximal reduction rate of VEP amplitude during surgery (MaxRed%), more than 66.7% to 70%. The VFL at 1 month after surgery (VFL1M) and the VFL at the final follow-up (Final VFL) were significantly related to MaxRed% more than 60.7%. CONCLUSION: VAL1M, Final VAL, VFL1M, and Final VFL could be significantly predicted by the value of RedEnd% and MaxRed% in direct clipping of Al-Rodhan group Ia, Ib, and II paraclinoid ICA aneurysms with anterior clinoidectomy.

The generalized linear mixed model (GLMM) is one of the most common method in the analysis of longitudinal and clustered data in biological sciences. However, issues of model complexity and misspecification can occur when applying the GLMM. To address these issues, we extend the standard GLMM to a nonlinear mixed-effects model based on quasi-linear modeling. An estimation algorithm for the proposed model is provided by extending the penalized quasi-likelihood and the restricted maximum likelihood which are known in the GLMM inference. Also, the conditional AIC is formulated for the proposed model. The proposed model should provide a more flexible fit than the GLMM when there is a nonlinear relation between fixed and random effects. Otherwise, the proposed model is reduced to the GLMM. The performance of the proposed model under model misspecification is evaluated in several simulation studies. In the analysis of respiratory illness data from a randomized controlled trial, we observe the proposed model can capture heterogeneity; that is, it can detect a patient subgroup with specific clinical character in which the treatment is effective.

Clustering is a major unsupervised learning algorithm and is widely applied in data mining and statistical data analyses. Typical examples include k-means, fuzzy c-means, and Gaussian mixture models, which are categorized into hard, soft, and model-based clusterings, respectively. We propose a new clustering, called Pareto clustering, based on the Kolmogorov–Nagumo average, which is defined by a survival function of the Pareto distribution. The proposed algorithm incorporates all the aforementioned clusterings plus maximum-entropy clustering. We introduce a probabilistic framework for the proposed method, in which the underlying distribution to give consistency is discussed. We build the minorize-maximization algorithm to estimate the parameters in Pareto clustering. We compare the performance with existing methods in simulation studies and in benchmark dataset analyses to demonstrate its highly practical utilities.

The kernel canonical correlation analysis based U-statistic (KCCU) is being used to detect nonlinear gene–gene co-associations. Estimating the variance of the KCCU is however computationally intensive. In addition, the kernel canonical correlation analysis (kernel CCA) is not robust to contaminated data. Using a robust kernel mean element and a robust kernel (cross)-covariance operator potentially enables the use of a robust kernel CCA, which is studied in this paper. We first propose an influence function-based estimator for the variance of the KCCU. We then present a non-parametric robust KCCU, which is designed for dealing with contaminated data. The robust KCCU is less sensitive to noise than KCCU. We investigate the proposed method using both synthesized and real data from the Mind Clinical Imaging Consortium (MCIC). We show through simulation studies that the power of the proposed methods is a monotonically increasing function of sample size, and the robust test statistics bring incremental gains in power. To demonstrate the advantage of the robust kernel CCA, we study MCIC data among 22,442 candidate Schizophrenia genes for gene–gene co-associations. We select 768 genes with strong evidence for shedding light on gene–gene interaction networks for Schizophrenia. By performing gene ontology enrichment analysis, pathway analysis, gene–gene network and other studies, the proposed robust methods can find undiscovered genes in addition to significant gene pairs, and demonstrate superior performance over several of current approaches.

Pancreatic ductal adenocarcinoma (PDAC) is the most life‐threating disease among all digestive system malignancies. We developed a blood mRNA PDAC screening system using real‐time detection PCR to detect the expression of 56 genes, to discriminate PDAC from noncancer subjects. We undertook a clinical study to assess the performance of the developed system. We collected whole blood RNA from 53 PDAC patients, 102 noncancer subjects, 22 patients with chronic pancreatitis, and 23 patients with intraductal papillary mucinous neoplasms in a per protocol analysis. The sensitivity of the system for PDAC diagnosis was 73.6% (95% confidence interval, 59.7%‐84.7%). The specificity for noncancer volunteers, chronic pancreatitis, and patients with intraductal papillary mucinous neoplasms was 64.7% (54.6%‐73.9%), 63.6% (40.7%‐82.8%), and 47.8% (26.8%‐69.4%), respectively. Importantly, the sensitivity of this system for both stage I and stage II PDAC was 78.6% (57.1%‐100%), suggesting that detection of PDAC by the system is not dependent on the stage of PDAC. These results indicated that the screening system, relying on assessment of changes in mRNA expression in blood cells, is a viable alternative screening strategy for PDAC.

Abstract In the classical discriminant analysis, when two multivariate normal distributions with equal variance–covariance matrices are assumed for two groups, the classical linear discriminant function is optimal with respect to maximizing the standardized difference between the means of two groups. However, for a typical case‐control study, the distributional assumption for the case group often needs to be relaxed in practice. Komori et al. (Generalized t‐statistic for two‐group classification. Biometrics 2015, 71: 404–416) proposed the generalized t‐statistic to obtain a linear discriminant function, which allows for heterogeneity of case group. Their procedure has an optimality property in the class of consideration. We perform a further study of the problem and show that additional improvement is achievable. The approach we propose does not require a parametric distributional assumption on the case group. We further show that the new estimator is efficient, in that no further improvement is possible to construct the linear discriminant function more efficiently. We conduct simulation studies and real data examples to illustrate the finite sample performance and the gain that it produces in comparison with existing methods.