Frailty transitions in the San Antonio Longitudinal Study of Aging

OBJECTIVES: To examine frailty transitions in Mexican American (MA) and European American (EA) older adults. DESIGN: Longitudinal, observational cohort study. SETTING: Socioeconomically diverse neighborhoods in San Antonio, Texas. PARTICIPANTS: Three hundred twelve MA and 285 EA community-dwelling older adults (≥ 65) with frailty information at baseline (1992-1996) and transition information at follow-up (2000/01) in the San Antonio Longitudinal Study of Aging. MEASUREMENTS: Five frailty characteristics (weight loss, exhaustion, weakness, slowness, and low physical activity), frailty score (0-5), and overall frailty state (nonfrail = 0 characteristics, prefrail = 1 or 2, frail = ≥ 3) were assessed at baseline. Transitions (progressed, regressed, or no change) were assessed for frailty score and state. Odds ratios (ORs) of progression and regression in individual characteristics were estimated using generalized estimating equations adjusted for age, sex, ethnic group, socioeconomic status, comorbidity, diabetes, and follow-up interval. RESULTS: Diabetes mellitus with macrovascular complications (OR = 1.84, 95% confidence interval (CI) = 1.02-3.33), fewer years of education (OR = 0.96, 95% CI = 0.93-1.0) and follow-up interval (OR = 1.3, 95% CI = 1.17-1.46) were significant predictors of progression in any frailty characteristic. Mortality increased with greater frailty state, and prefrail individuals were more likely than frail individuals to regress. CONCLUSION: Diabetes mellitus with macrovascular complications and fewer years of education are important predictors of progression in any frailty characteristic. Because of greater risk of death than for the nonfrail state and greater likelihood of regression than for the frail state, the prefrail state may be an optimal target for intervention.ope

Evaluation of the Gini Coefficient in Spatial Scan Statistics for Detecting Irregularly Shaped Clusters

Spatial scan statistics with circular or elliptic scanning windows are commonly used for cluster detection in various applications, such as the identification of geographical disease clusters from epidemiological data. It has been pointed out that the method may have difficulty in correctly identifying non-compact, arbitrarily shaped clusters. In this paper, we evaluated the Gini coefficient for detecting irregularly shaped clusters through a simulation study. The Gini coefficient, the use of which in spatial scan statistics was recently proposed, is a criterion measure for optimizing the maximum reported cluster size. Our simulation study results showed that using the Gini coefficient works better than the original spatial scan statistic for identifying irregularly shaped clusters, by reporting an optimized and refined collection of clusters rather than a single larger cluster. We have provided a real data example that seems to support the simulation results. We think that using the Gini coefficient in spatial scan statistics can be helpful for the detection of irregularly shaped clusters.ope

Comparison of resampling methods for dealing with imbalanced data in binary classification problem

A class imbalance problem arises when one class outnumbers the other class by a large proportion in binary data. Studies such as transforming the learning data have been conducted to solve this imbalance problem. In this study, we compared resampling methods among methods to deal with an imbalance in the classification problem. We sought to find a way to more effectively detect the minority class in the data. Through simulation, a total of 20 methods of over-sampling, under-sampling, and combined method of over- and under-sampling were compared. The logistic regression, support vector machine, and random forest models, which are commonly used in classification problems, were used as classifiers. The simulation results showed that the random under sampling (RUS) method had the highest sensitivity with an accuracy over 0.5. The next most sensitive method was an over-sampling adaptive synthetic sampling approach. This revealed that the RUS method was suitable for finding minority class values. The results of applying to some real data sets were similar to those of the simulation.restrictio

Clinical characteristics and treatment outcomes of patients with macrolide-resistant Mycobacterium avium complex pulmonary disease: a systematic review and meta-analysis

BACKGROUND: Macrolide is a key drug in the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). Macrolide-resistant MAC is gaining importance, but there are little data in clinical characteristics and treatment outcomes of macrolide-resistant MAC-PD (MR-MAC-PD). METHODS: We performed a systematic review and meta-analysis of published studies reporting clinical characteristics and treatment outcomes of patients with MR-MAC-PD. Risk of bias was assessed using the modified Newcastle-Ottawa Scale. RESULTS: Nine studies (seven retrospective and two prospective) comprising 319 patients were identified through a database search. Around 73% were women, and 52% had the fibrocavitary form. Pooled sputum culture conversion rate after combined multiple antibiotics or surgical resection was 21% (95% confidence interval [CI], 14-30%), and the one-year all-cause mortality was 10% (95% CI, 5-20%). There was no significant difference in treatment outcomes between nodular bronchiectatic and fibrocavitary types. CONCLUSIONS: Even combination therapy with fluoroquinolone, aminoglycoside, and surgical resection, the treatment outcomes of MR-MAC-PD were poor. The investigation of new treatment modalities is urgent.ope

Trends in statistical methods in articles published in Archives of Plastic Surgery between 2012 and 2017

This review article presents an assessment of trends in statistical methods and an evaluation of their appropriateness in articles published in the Archives of Plastic Surgery (APS) from 2012 to 2017. We reviewed 388 original articles published in APS between 2012 and 2017. We categorized the articles that used statistical methods according to the type of statistical method, the number of statistical methods, and the type of statistical software used. We checked whether there were errors in the description of statistical methods and results. A total of 230 articles (59.3%) published in APS between 2012 and 2017 used one or more statistical method. Within these articles, there were 261 applications of statistical methods with continuous or ordinal outcomes, and 139 applications of statistical methods with categorical outcome. The Pearson chi-square test (17.4%) and the Mann-Whitney U test (14.4%) were the most frequently used methods. Errors in describing statistical methods and results were found in 133 of the 230 articles (57.8%). Inadequate description of P-values was the most common error (39.1%). Among the 230 articles that used statistical methods, 71.7% provided details about the statistical software programs used for the analyses. SPSS was predominantly used in the articles that presented statistical analyses. We found that the use of statistical methods in APS has increased over the last 6 years. It seems that researchers have been paying more attention to the proper use of statistics in recent years. It is expected that these positive trends will continue in APS.ope

Pregnancy outcomes of elective induction in low-risk term pregnancies: A propensity-score analysis

We investigated the mode of delivery and perinatal outcomes in low-risk pregnant women whose labor was electively induced or expectantly managed at term.Healthy women with viable, vertex singleton pregnancies at 37 to 40 weeks of gestation were included. Women electively induced (n = 416) in each week (37-37, 38-38, 39-39, 40-40 weeks) were compared with pregnant women with spontaneous labor (n = 487). The primary outcome was mode of delivery. A propensity score (PS) was derived using logistic regression to model the probability of elective induction group as a function of potential confounders. Altogether, 284 women with elective induction were matched with 284 women who underwent expectant management to create a PS-matched population. All analysis was performed using SAS software, version 9.4 (SAS Institute Inc., Cary, NC). All P values reported of the significance level was set at <.05.There are no significant differences of delivery mode, neonatal intensive care unit (NICU) admission, and neonatal complication between PS-matched groups. Incidence of antepartum complications showed higher in the elective induction group compared to the spontaneous labor group (P = .04). When comparing each gestational week, incidence of NICU admission at 38 weeks in the elective induction group [10/74 (13.5%)] was significantly higher than in and the spontaneous labor group [2/74 (2.7%)] (P = .04).Elective induction of labor at term is not associated with increased risk of cesarean delivery. However, overall incidence of NICU admission at 38 gestational weeks seems to be increased in elective induction.ope

SRG3에 의한 SWI/SNF 염색사 리모델링 복합체의 안정화 및 BAP1이 흉선세포 분화에 미치는 영향에 대한 연구

학위논문 (박사)-- 서울대학교 대학원 : 생명과학부, 2015. 2. 성노현.T cells are major mediators of cell-mediated immune responses. T cell progenitors originating in the bone marrow enter the thymus, and then differentiate, undergo selection, and mature into functional T cells through a series of organized and complicated developmental stages. These multiple steps in T cell development are regulated by the transcriptional control of lineage-specific genes and by the sequential rearrangement of T cell receptor (TCR) genes. Switching the transcription of various genes, including Notch, GATA-3, E2A/HEB, Id proteins, c-Myb, ThPOK, Runx complex, and Ikaros family genes, on or off is critical for lineage commitment in T cells. In addition, the β-selection and positive selection, which depend on the successful rearrangement of TCR genes, are essential for the production of mature T cells. Chromatin status, which is regulated by histone modification enzymes and chromatin remodeling complex, ultimately determines whether gene expression is turned on or off. Here, I studied the major components of the murine SWI/SNF complex. It was found that BRG1, SNF5, and BAF60a are targeted for ubiquitylation and degradation, but that SRG3 can protect them from degradation. Previous studies have shown that the SWI/SNF ATP-dependent chromatin remodeling complex is essential for the developmental transitions of thymocytes. In many studies, the stability of the SWI/SNF complex has been shown to be regulated by ubiquitylation. In particular, SRG3 stabilizes SNF5, BRG1 and BAF60a by attenuating their proteasomal degradation, suggesting its essential role in stabilization of the SWI/SNF complex. It was also found that CHFR, an E3 ubiquitin ligase and known tumor suppressor that plays an essential role in cell cycle control and tumorigenesis, interacts with and ubiquitylates BRG1, SNF5, and BAF60a of the SWI/SNF complex, targeting them for degradation through a proteasome-mediated pathway. Moreover, It was found that SRG3 stabilizes these components by blocking their interaction with CHFR. Second, I investigated the function of Bap1, a deubiquitinase involved in the regulation of cell growth and proliferation, in thymocyte development. Bap1-deficient mice showed developmental retardation in embryo and expansion of the myeloid lineage. In this study, to gain insight into the contributions of Bap1 to T cell development, the mouse Bap1 gene was deleted cell specifically, using Lck-Cre-producing mouse strains. The total thymocyte number was significantly reduced in Bap1 conditional knockout mice. It was found that Bap1 plays a critical role in pre-TCR signaling and TCR-mediated T cell development and activation. Bap1-deficient T cells displayed the block from stage double negative (DN) 3 to DN4, and they exhibited reduced expression of TCRβ compared with controls. Thymic positive selection was also significantly decreased when Bap1 was knocked out in a TCR transgenic background. TCR-mediated signaling events, including calcium flux and extracellular signal-regulated kinase (ERK) activation, were impaired in Bap1-deficient mice. Additionally, peripheral T cells were not efficiently activated upon TCR stimulation. Taken together, these findings suggest that Bap1 is a critical component of T cell development and that it participates in TCR signaling events required for thymocyte activation. From these results, I conclude that: 1) the SWI/SNF chromatin remodeling complex for ordinary T cell development is stabilized by SRG3 through the blockade of CHFR activity, and 2) Bap1 expression in pre-TCR and TCR signal transduction is critical for successful thymocyte development and maturation.TABLE OF CONTENTS ABSTRACT…………………………………......………......…....……i TABLE OF CONTENTS……………………...........………........….iii LIST OF FIGURES……………………………………..................….v CHAPTER I. INTRODUCTION.……………………………...........1 I-1. Thymocyte development and TCR signaling.......................................2 I-2. The SWI/SNF chromatin remodeling complexes.................................5 I-3. SRG3, a scaffold subunit of the SWI/SNF complex............................7 I-4. The function of SWI/SNF complex in thymocyte development........10 I-5. The Ubiquitin-Proteasome system.....................................................11 I-6. CHFR, an E3 ubiquitin ligase.............................................................13 I-7. BAP1, a deubiquitinating enzyme......................................................14 I-8. The function of BAP1 during hematopoiesis.....................................19 CHAPTER II. MATERIALS AND METHODS..........................21 CHAPTER III. RESULTS.................................................................28 III-1. SRG3 stabilizes the SWI/SNF complex by blocking CHFR mediated ubiquitylation and degradation..................................................29 III-2. Thymocyte-specific deletion of the deubiquitinase Bap1 impairs thymocyte development and activation.....................................................45 CHAPTER IV. DISCUSSION...........................................................75 IV-1. SRG3 stabilizes the SWI/SNF complex by blocking CHFR mediated ubiquitylation and degradation..................................................76 IV-2. Thymocyte-specific deletion of the deubiquitinase Bap1 impairs thymocyte development and activation.....................................................81 REFERENCES.....................................................................................88Docto

Some Facts That You Might Be Unaware of About the P-Value.

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Restricted Mean Survival Time for Survival Analysis: A Quick Guide for Clinical Researchers

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Optimizing the maximum reported cluster size in the spatial scan statistic for ordinal data

The spatial scan statistic is an important tool for spatial cluster detection. There have been numerous studies on scanning window shapes. However, little research has been done on the maximum scanning window size or maximum reported cluster size. Recently, Han et al. proposed to use the Gini coefficient to optimize the maximum reported cluster size. However, the method has been developed and evaluated only for the Poisson model. We adopt the Gini coefficient to be applicable to the spatial scan statistic for ordinal data to determine the optimal maximum reported cluster size. Through a simulation study and application to a real data example, we evaluate the performance of the proposed approach. With some sophisticated modification, the Gini coefficient can be effectively employed for the ordinal model. The Gini coefficient most often picked the optimal maximum reported cluster sizes that were the same as or smaller than the true cluster sizes with very high accuracy. It seems that we can obtain a more refined collection of clusters by using the Gini coefficient. The Gini coefficient developed specifically for the ordinal model can be useful for optimizing the maximum reported cluster size for ordinal data and helpful for properly and informatively discovering cluster patterns.ope