Analytically Tractable Models for Decision Making under Present Bias

Time-inconsistency is a characteristic of human behavior in which people plan for long-term benefits but take actions that differ from the plan due to conflicts with short-term benefits. Such time-inconsistent behavior is believed to be caused by present bias, a tendency to overestimate immediate rewards and underestimate future rewards. It is essential in behavioral economics to investigate the relationship between present bias and time-inconsistency. In this paper, we propose a model for analyzing agent behavior with present bias in tasks to make progress toward a goal over a specific period. Unlike previous models, the state sequence of the agent can be described analytically in our model. Based on this property, we analyze three crucial problems related to agents under present bias: task abandonment, optimal goal setting, and optimal reward scheduling. Extensive analysis reveals how present bias affects the condition under which task abandonment occurs and optimal intervention strategies. Our findings are meaningful for preventing task abandonment and intervening through incentives in the real world

Computer simulation analysis of fracture dislocation of the proximal interphalangeal joint using the finite element method.

Stress is a proximal interphalangeal (PIP) joint model was analyzed by the two-dimensional and three-dimensional finite element methods (FEM) to study the onset mechanisms of the middle phalangeal base fracture. The structural shapes were obtained from sagittally sectioned specimens of the PIP joint for making FEM models. In those models, four different material properties were given corresponding to cortical bone, subchondral bone, cancellous bone and cartilage. Loading conditions were determined by estimating the amount and position of axial pressure added to the middle phalanx. A general finite element program (MARC) was used for computer simulation analysis. The results of the fracture experiments compared with the clinical manifestation of the fractures justify the applicability of the computer simulation models using FEM analysis. The stress distribution changed as the angle of the PIP joint changed. Concentrated stress was found on the volar side of the middle phalangeal base in the hyperextension position, and was found on the dorsal side in the flexion position. In the neutral position, the stress was found on both sides. Axial stress on the middle phalanx causes three different types of fractures (volar, dorsal and both) depending upon the angle of the PIP joint. These results demonstrate that the type of PIP joint fracture dislocation depends on the angle of the joint at the time of injury. The finite element method is one of the most useful methods for analyzing the onset mechanism of fractures.</p

Efficient identification of candidate tumor suppressor genes using retroviral insertional mutagenesis in mice with genomic instability

Division of Functional Genomic

Clinical Validation of a Multiplex Kit for RAS Mutations in Colorectal Cancer: Results of the RASKET (RAS KEy Testing) Prospective, Multicenter Study

AbstractBackgroundRAS (KRAS and NRAS) testing is required to predict anti-epidermal growth factor receptor (EGFR) treatment efficacy in metastatic colorectal cancer (CRC). Although direct sequencing (DS) with manual microdissection (MMD) is widely used, a diagnostic kit providing rapid detections of RAS mutations would be clinically beneficial. We evaluated the MEBGENTM RASKET KIT (RASKET KIT), a multiplex assay using PCR-reverse sequence specific oligonucleotide and xMAP® technology to concurrently detect exon 2, 3, and 4 RAS mutations in a short turnaround time (4.5h/96-specimens).MethodsFormalin-fixed paraffin-embedded (FFPE) tissues were obtained from 308 consenting patients with histologically-confirmed CRC at six hospitals in Japan. For the RASKET KIT, we used only 50–100ng DNA from each FFPE specimen not processed by MMD. The primary endpoint was the concordance rate between RAS mutations identified with the RASKET KIT and two reference assays (DS with MMD and TheraScreen® K-RAS Mutation Kit). As the secondary endpoints, we evaluated the concordance rate between DS and the RASKET KIT for RAS mutations in the wild-type KRAS exon 2 population and the genotyping performance of the RASKET KIT compared with DS.FindingsAmong 307 analyzable specimens, the reference assays detected 140 (45.6%, 140/307) RAS mutations: 111 KRAS exon 2 and 29 other (minor) RAS mutations. The RASKET KIT detected 143 (46.6%, 143/307) mutations: 114 KRAS exon 2 and 29 minor RAS mutations. The between-method concordance rate was 96.7% (297/307) (95% CI: 94.1–98.4%). Minor RAS mutations were detected in 15.7% (30/191) of the wild-type KRAS exon 2 population (n=191); the concordance rate was 98.4% (188/191) (95% CI: 95.5–99.7%). The concordance rate of RAS genotyping was 100% (139/139) (95% CI: 97–100%).InterpretationThe RASKET KIT provides rapid and precise detections of RAS mutations and consequently, quicker and more effective anti-EGFR therapy for CRC (Study ID: UMIN000011784).FundingMedical & Biological Laboratories Co., Ltd. (MBL). MBL had roles in study design, data collection, data analysis, and writing of the report for the study

Impact of laparoscopic surgery on short‐term and long‐term outcomes in elderly obese patients with colon cancer

[Background] Laparoscopic surgery is reported to be useful in obese or elderly patients with colon cancer, who are at increased risk of postoperative complications because of comorbidities and physical decline. However, its usefulness is less clear in patients who are both elderly and obese and may be at high risk of complications. [Methods] Data for obese patients (body mass index ≥25) who underwent laparoscopic or open surgery for stage II or III colon cancer between January 2009 and December 2013 were collected by the Japan Society of Laparoscopic Colorectal Surgery. Surgical outcomes, postoperative complications, and relapse-free survival (RFS) were compared between patients who underwent open surgery and those who underwent laparoscopic surgery according to whether they were elderly (≥70 y) or nonelderly (<70 y). [Results] Data of 1549 patients (elderly, n = 598; nonelderly, n = 951) satisfied the selection criteria for analysis. Length of stay was shorter and surgical wound infection was less common in elderly obese patients who underwent laparoscopic surgery than in those underwent open surgery. There were no significant between-group differences in overall complications, anastomotic leakage, ileus/small bowel obstruction, or RFS. There were also no significant differences in RFS after laparoscopic surgery according to patient age. [Conclusion] Laparoscopic surgery is safe in elderly obese patients with colon cancer and does not worsen their prognosis. There was no significant difference in the effectiveness of laparoscopic surgery between obese patients who were elderly and those who were nonelderly

Vectors expressing efficient RNA decoys achieve the long-term suppression of specific microRNA activity in mammalian cells

Whereas the strong and stable suppression of specific microRNA activity would be essential for the functional analysis of these molecules, and also for the development of therapeutic applications, effective inhibitory methods to achieve this have not yet been fully established. In our current study, we tested various RNA decoys which were designed to efficiently expose indigestible complementary RNAs to a specific miRNA molecule. These inhibitory RNAs were at the same time designed to be expressed in lentiviral vectors and to be transported into the cytoplasm after transcription by RNA polymerase III. We report the optimal conditions that we have established for the design of such RNA decoys (we term these molecules TuD RNAs; tough decoy RNAs). We finally demonstrate that TuD RNAs induce specific and strong biological effects and also show that TuD RNAs achieve the efficient and long-term-suppression of specific miRNAs for over 1 month in mammalian cells

Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20–89 years: A cross-sectional nationwide study in Japan

Background The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. Methods We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. Results The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. Conclusion The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex