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To reduce unnecessary prostate biopsies (Pbx), better discrimination is needed. To identify clinically significant prostate cancer (CSPC) we determined the performance of LacdiNAc‐glycosylated prostate‐specific antigen (LDN‐PSA) and LDN‐PSA normalized by prostate volume (LDN‐PSAD). We retrospectively measured LDN‐PSA, total PSA (tPSA), and free PSA/tPSA (F/T PSA) values in 718 men who underwent a Pbx in 3 academic urology clinics in Japan and Canada (Pbx cohort) and in 174 PC patients who subsequently underwent radical prostatectomy in Australia (preop‐PSA cohort). The assays were evaluated using the area under the receiver operating characteristics curve (AUC) and decision curve analyses to discriminate CSPC. In the Pbx cohort, LDN‐PSAD (AUC 0.860) provided significantly better clinical performance for discriminating CSPC compared with LDN‐PSA (AUC 0.827, P = 0.0024), PSAD (AUC 0.809, P

Various types of circulating tumor cell (CTC) detection systems have recently been developed that show a high CTC detection rate. However, it is a big challenge to find a system that can provide better prognostic value than CellSearch in head-to-head comparison. We have developed a novel semi-automated CTC enumeration system (fluidic cell microarray chip system, FCMC) that captures CTC independently of tumor-specific markers or physical properties. Here, we compared the CTC detection sensitivity and the prognostic value of FCMC with CellSearch in breast cancer patients. FCMC was validated in preclinical studies using spike-in samples and in blood samples from 20 healthy donors and 22 breast cancer patients in this study. Using spike-in samples, a statistically higher detection rate (p = 0.010) of MDA-MB-231 cells and an equivalent detection rate (p = 0.497) of MCF-7 cells were obtained with FCMC in comparison with CellSearch. The number of CTC detected in samples from patients that was above a threshold value as determined from healthy donors was evaluated. The CTC number detected using FCMC was significantly higher than that using CellSearch (p = 0.00037). CTC numbers obtained using either FCMC or CellSearch had prognostic value, as assessed by progression free survival. The hazard ratio between CTC + and CTC − was 4.229 in CellSearch (95% CI, 1.31 to 13.66; p = 0.01591); in contrast, it was 11.31 in FCMC (95% CI, 2.245 to 57.0; p = 0.000244). CTC detected using FCMC, like the CTC detected using CellSearch, have the potential to be a strong prognostic factor for cancer patients.

The performance indicator called limit of detection for microarray platform (LODP) was defined in ISO 16578:2013. The methods to determine practical LODP were explored. In general, + 3 SD of the background is used as the signal strength of limit of detection and criteria for dividing positive and negative results. Since the negative signal had been defined differently for each microarray platform, signals obtained from Non-Probe Spots (NPS) installed on the microarrays were defined as the “background” of microarrays. LODP was determined as the lowest concentration of which the average signal exceeded Avg. + 3 SD of the background (NPS) and the signal was significantly different from those of the lower and higher adjacent concentration points measured with a diluted series of reference materials. For reliable qualitative analysis, the positive results can be defined as signals higher than those corresponding to LODP and negative results as lower signals, without determining limit of detection for all target probes. The use of LODP also enables comparisons of platform performances without checking sequence dependencies, and assists to select reliable and fitting platforms for experimental purposes.

Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen-glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c-index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively.

液状化に起因した地盤の側方流動に対する杭基礎設計法提案に向けた検討を行うため，せん断土槽内に杭配置，杭剛性等をパラメ－タとした模型杭を設置した地盤を作製し，加振により液状化が発生したせん断土槽を強制的に変形させることにより，側方流動現象を模擬した小型振動台実験および大型振動台実験を行い，実験時に計測した杭への作用力を液状化層およびそれより上部の非液状化層からの成分に分離し，各層からの杭への作用力上限値を杭配置をパラメ－タとした評価式で定式化した．また，大型振動台実験結果から側方流動時の地盤反力係数（杭と地盤のバネ値）と圧縮ひずみを算定した．なお，これらの検討により得られた成果を著者らが提案する側方流動に対する杭基礎設計法への反映事項とした．

A high-sensitivity immunoassay system with surface plasmon field-enhanced fluorescence spectrometry (SPFS) was constructed using a plastic sensor chip and then applied to the detection of total prostate-specific antigen (total PSA) and GalNAcβ1-4GlcNAc-linked prostate-specific antigen (LacdiNAc-PSA) in serum, to discriminate between prostate cancer (PC) and benign prostate hyperplasia (BPH). By using this automated SPFS immunoassay, the detection limit for total PSA in serum was as low as 0.04 pg/mL, and the dynamic range was estimated to be at least five digits. A two-step sandwich SPFS immunoassay for LacdiNAc-PSA was constructed using both the anti-PSA IgG antibody to capture PSA and Wisteria floribunda agglutinin (WFA) for the detection of LacdiNAc. The results of the LacdiNAc-PSA immunoassay with SPFS showed that the assay had a sensitivity of 20.0 pg/mL and permitted the specific distinction between PC and BPH within the PSA gray zone. These results suggested that high-sensitivity automated SPFS immunoassay systems might become a powerful tool for the diagnosis of PC and other diseases.

Immunochromatography (IC) is an antigen-detection assay that plays an important role in the rapid diagnosis of influenza virus because the protocol is short time and easy to use. Despite the usability of IC, the sensitivity is approximately 10(3) pfu per reaction. In addition, antigen-antibody interaction-based method cannot be used for the detection of influenza viruses with major antigenic change. In this study, we established the use of fluorescent immunochromatography (FLIC) to detect a broad spectrum of H5 subtype influenza A viruses. This method has improved sensitivity 10-100 fold higher than traditional IC because of the use of fluorescent conjugated beads. Our Type-E FLIC kit detected all of the H5 subtype influenza viruses that were examined, as well as recombinant hemagglutinin (HA) proteins (rHAs) belonging to the Eurasian H5 subtype viruses and the Type-N diagnosed North American H5 subtype influenza A viruses. Thus, this kit has the improved potential to detect H5 subtype influenza viruses of different clades with both Type-E and Type-N FLIC kits. Compared with PCR-based diagnosis, FLIC has a strong advantage in usability, because the sample preparation required for FLIC is only mix-and-drop without any additional steps such as RNA extraction. Our results can provide new strategies against the spread and transmission of HPAI H5N1 viruses in birds and mammals including humans.

No current circulating tumor cell (CTC) enumeration system provides better prognostic value than CellSearch. We have developed a novel semi-automated CTC enumeration system (fluidic cell microarray chip system, FCMC) that captures CTC independently of tumor-specific markers or physical properties. This system was validated in preclinical studies and in blood samples from 20 healthy donors and 22 breast cancer patients in this study. Using spike-in samples, a statistically higher detection rate (p = 0.010) of MDA-MB-231 cells and an equivalent detection rate (p = 0.497) of MCF-7 cells were obtained with FCMC in comparison with CellSearch. The number of CTC detected in samples from patients that was above a threshold value as determined from healthy donors was evaluated. The CTC number detected using FCMC was significantly higher than that using CellSearch (p = 0.00037). CTC numbers obtained using either FCMC or CellSearch had prognostic value, as assessed by time-to-treatment-failure. The hazard ratio between CTC+ and CTC- was 4.043 in CellSearch (95% CI, 1.248 to 13.10; p = 0.01985); in contrast, it was 10.97 in FCMC (95% CI, 2.18 to 55.21; p = 0.003662). CTC detected using FCMC have the potential to be a better prognostic factor than CTC detected using CellSearch. Citation Format: Takeshi Sawada, Jungo Araki, Toshinari Yamashita, Manami Masubuchi, Tsuneko Chiyoda, Mayu Yunokawa, Kumiko Hoshi, Shoichi Tao, Shohei Yamamura, Shouki Yatsushiro, Kaori Abe, Masatoshi Kataoka, Tatsu Shimoyama, Yoshiharu Maeda, Katsumasa Kuroi, Kenji Tamura, Tsuneo Sawazumi, Hironobu Minami, Yoshihiko Suda, Fumiaki Koizumi. Prognostic impact of CTC detected using a novel fluidic cell microarray chip CTC detection system in patients with breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 500.

The frequency distribution of precipitation changes from inverse J-shaped type, through the exponential, to normal type with increase in a length of lumped period. The seasonal and regional characteristics of the change with lumped period from 1 hour to 30 days are investigated for AMeDAS precipitation data sets. The gamma distribution is employed as a distribution model fitted to the observed data and the method of maximum-entropy as a method of the parameter estimation. The shape of a frequency distribution can be expressed quantitatively by the information content due to logarithmic geometric mean. The following findings are drawn from the frequency analysis: 1) Lumped period in which a frequency distribution is the exponential one for winter-half-year is rather short on the Japan Sea side and rather long on the Pacific Ocean side. The regional difference is understood by considering that main precipitation-induced disturbance is different for each region and each disturbance has its own time-series characteristics. 2) As for variation of information content due to logarithmic geometric mean in short-term, there is latitudinal difference in the Japanese Islands, which corresponds with difference between precipitation characteristics represented by rain shower and those by continuous rain.

Lateral flow tests also known as Immunochromatography (IC) is an antigen-detection method conducted on a nitrocellulose membrane that can be completed in less than 20 min. IC has been used as an important rapid test for clinical diagnosis and surveillance of influenza viruses, but the IC sensitivity is relatively low (approximately 60%) and the limit of detection (LOD) is as low as 10³ pfu per reaction. Recently, we reported an improved IC assay using antibodies conjugated with fluorescent beads (fluorescent immunochromatography; FLIC) for subtyping H5 influenza viruses (FLIC-H5). Although the FLIC strip must be scanned using a fluorescent reader, the sensitivity (LOD) is significantly improved over that of conventional IC methods. In addition, the antibodies which are specific against the subtypes of influenza viruses cannot be available for the detection of other subtypes when the major antigenicity will be changed. In this study, we established the use of FLIC to type seasonal influenza A and B viruses (FLIC-AB). This method has improved sensitivity to 100-fold higher than that of conventional IC methods when we used several strains of influenza viruses. In addition, FLIC-AB demonstrated the ability to detect influenza type A and influenza type B viruses from clinical samples with high sensitivity and specificity (Type A: sensitivity 98.7% (74/75), specificity 100% (54/54), Type B: sensitivity 100% (90/90), specificity 98.2% (54/55) in nasal swab samples) in comparison to the results of qRT-PCR. And furthermore, FLIC-AB performs better in the detection of early stage infection (under 13 h) than other conventional IC methods. Our results provide new strategies to prevent the early-stage transmission of influenza viruses in humans during both seasonal outbreaks and pandemics.

While silver halide photosensitive materials offer superiority in image quality -- both in color and black-and-white -- they require chemical solutions for processing, and this can be a drawback. To overcome this, researchers turned to the thermal development of silver halide photographic materials, and met their first success with black-and-white images. Later, with the development of the Konica Dry Color System, color images were finally obtained from a completely dry thermal development system, without the use of water or chemical solutions. The dry color system is characterized by a novel chromogenic color image-forming technology and comprises four processes. (1) With the application of heat, a color developer precursor (CDP) decomposes to generate a p-phenylenediamine color developer (CD). (2) The CD then develops silver salts. (3) Oxidized CD then reacts with couplers to generate color image dyes. (4) Finally, the dyes diffuse from the system's photosensitive sheet to its image-receiving sheet. The authors have analyzed the kinetics of each of the system's four processes. In this paper, they report the kinetics of the system's first process, color developer (CD) generation.© (1991) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.