Real-time cheat-free gaming on the basis of time-stamp service

A cheat-proof protocol for real-time gaming is proposed under the assumption that time-stamp servers issue serially numbered time stamps honestly and are available near every player, i.e., they exist everywhere in the Internet. With this protocol, each player sends its action to the other player and also sends its hash to the nearest time-stamp server. The time-stamp server sends the signed hash with the time and a serial number back to the player. The actions are checked to verify that they are compatible with the hashes, and the signed hashes are checked to verify that they have the correct time and the serial numbers are contiguous. The only latency in this protocol is the travel time of the packet from one player to another. In comparison with other existing protocols, we confirm that the proposed protocol is as fast as and more secure than the fair synchronization protocol, the fastest existing protoco

Antiadhesive nanosome elicits role of glycocalyx of tumor cell-derived exosomes in the organotropic cancer metastasis

Despite emerging importance of tumor cells-derived exosomes in cancer metastasis, the heterogeneity of exosome populations has largely hampered systemic characterization of their molecular composition, biogenesis, and functions. This study communicates a novel method for predicting and targeting pre-metastatic sites based on an exosome model fluorescent cancer glyconanosomes displaying N-glycans of cultured tumor cells. Glycoblotting by antiadhesive quantum dots provides a nice tool to shed light on the pivotal functions of the glycocalyx reconstructed from four cancer cell types without bias due to other compositions of exosomes. In vivo imaging revealed that circulation, clearance, and organotropic biodistribution of cancer glyconanosomes in mice depend strongly on cancer cell-type-specific N-glycosylation patterns, the compositions of key glycotypes, particularly dominant abundances of high mannose-type N-glycans and the position-specific sialylation. Notably, organ biodistribution of cancer glyconanosomes is reproducible artificially by mimicking cancer cell-typespecific N-glycosylation patterns, demonstrating that nanosomal glycoblotting method serves as promising tools for predicting and targeting pre-metastatic sites determined by the glycocalyx of extracellular vesicles disseminated from the primary cancer site

Analysis of Closed Claims in the Clinical Management of Rheumatoid Arthritis in Japan

Background: Despite an increasing awareness of the risk of medical errors, few data sources are available to highlight the characteristics and patterns of medical errors in the clinical management of rheumatoid arthritis (RA). The present study aimed to evaluate medical malpractice claims associated with the management of RA and other autoimmune connective tissue diseases (ACTDs). Methods: We analyzed 38 ACTD-associated closed claims extracted from a total of 8530 claims processed between July 2004 and June 2014 by the Tokyo headquarters office of Sompo Japan Nipponkoa Incorporated, a leading malpractice insurer in Japan. Results: RA was the most common ACTD assessed in this study, accounting for 20 cases. Although the male-to-female ratio among these cases was 5:15, in accordance with the general demographic distribution of RA, the proportion of patients older than 60 years (77.8%) was relatively high as the general range of RA susceptibility is 30–50 years. The analysis of allegation types among RA cases revealed statistically significant differences from non-RA cases (Fisher's exact test) as well as the following key findings: diagnosis-related allegations were absent (P < 0.01), whereas medication-related allegations were distinctively common (P = 0.02). Clinical processes related to the assessment process were most vulnerable to breakdown and leading to negligence identified with subsequent medication-related allegations, particularly among RA cases. Conclusions: The characteristics of malpractice claims associated with RA management, including the high frequency of medication-related allegations, breakdowns in the assessment process, and high claim numbers among patients older than 60 years, suggest the importance of caution exercised by physicians when administering immunosuppressants for the clinical treatment of RA

Selective reaction monitoring approach using structure-defined synthetic glycopeptides for validating glycopeptide biomarkers pre-determined by bottom-up glycoproteomics

Clusterin is a heavily glycosylated protein that is upregulated in various cancer and neurological diseases. The findings by the Hancock and Iliopoulos group that levels of the tryptic glycopeptide derived from plasma clusterin, (372)Leu-Ala-Asn-Leu-Thr-Gln-Gly-Glu-Asp-Gln-Tyr-Tyr-Leu-Arg(385) with a biantennary disialyl N-glycan (A2G2S2 or FA2G2S2) at Asn374 differed significantly prior to and after curative nephrectomy for clear cell renal cell carcinoma (RCC) patients motivated us to verify the feasibility of this glycopeptide as a novel biomarker of RCC. To determine the precise N-glycan structure attached to Asn374, whether A2G2S2 is composed of the Neu5Ac alpha 2,3Gal or/and the Neu5Ac alpha 2,6Gal moiety, we synthesized key glycopeptides having one of the two putative isomers. Selective reaction monitoring assay using synthetic glycopeptides as calibration standards allowed top-down glycopeptidomics for the absolute quantitation of targeted label-free glycopeptides in a range from 313.3 to 697.5 nM in the complex tryptic digests derived from serum samples of RCC patients and healthy controls. Our results provided evidence that the Asn374 residue of human clusterin is modified dominantly with the Neu5Ac alpha 2,6Gal structure and the levels of clusterin bearing an A2G2S2 with homo Neu5Ac alpha 2,6Gal terminals at Asn374 decrease significantly in RCC patients as compared with healthy controls. The present study elicits that a new strategy integrating the bottom-up glycoproteomics with top-down glycopeptidomics using structure-defined synthetic glycopeptides enables the confident identification and quantitation of the glycopeptide targets pre-determined by the existing methods for intact glycopeptide profiling

Comparison of professionalism between emergency medicine resident physicians and faculty physicians: A multicenter cross-sectional study.

Professionalism is a critical competency for emergency medicine (EM) physicians, and professional behavior affects patient satisfaction. However, the findings of various studies indicate that there are differences in the interpretation of professionalism among EM resident physicians and faculty physicians. Using a cross-sectional survey, we aimed to analyze common challenges to medical professionalism for Japanese EM physicians and survey the extent of professionalism coursework completed during undergraduate medical education. We conducted a multicenter cross-sectional survey of EM resident physicians and faculty physicians at academic conferences and eight teaching hospitals in Japan using the questionnaire by Barry and colleagues. We analyzed the frequency of providing either the best or second-best answers to each scenario as the main outcome measure and compared the frequencies between EM resident physicians and EM faculty physicians. Fisher's exact test and the Wilcoxon rank sum test were used to analyze data. A total of 176 physicians (86 EM resident physicians and 90 EM faculty physicians) completed the survey. The response rate was 92.6%. The most challenging scenario presented to participants dealt with sexual harassment, and only 44.5% chose the best or second-best answers, followed by poor responses to the confidentiality scenario (69.9%). The frequency of either the best or second-best responses to the confidentiality scenario was significantly greater for EM resident physicians than for EM faculty physicians (77.1% versus 62.9%, p = 0.048). More participants in the EM resident physician group completed formal courses in medical professionalism than those in the EM faculty physician group (25.8% versus 5.5%, p < 0.01). Further, EM faculty physicians were less likely than EM resident physicians to provide acceptable responses in terms of confidentiality, and few of both had received professionalism training through school curricula. Continuous professionalism education focused on the prevention of sexual harassment and gender gap is needed for both EM resident physicians and faculty physicians in Japan