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Although radiation therapy is one of the most significant treatment modalities for localized prostate cancer, the prognostic factors for biochemical recurrence (BCR) regarding the treatment plan are unclear. We aimed to develop a novel dosiomics-based prediction model for BCR in patients with prostate cancer and clarify the correlations between the dosimetric factors and BCR.This study included 489 patients with localized prostate cancer (BCR: 96; no-BCR: 393) who received intensity modulated radiation therapy. A total of 2475 dosiomic features were extracted from the dose distributions on the prostate, clinical target volume (CTV), and planning target volume. A prediction model for BCR was trained on a training cohort of 342 patients. The performance of this model was validated using the concordance index (C-index) in a validation cohort of 147 patients. Another model was constructed using clinical variables, dosimetric parameters, and radiomic features for comparisons. Kaplan-Meier curves with log-rank analysis were used to assess the univariate discrimination based on the predictive dosiomic features.The dosiomic feature derived from the CTV was significantly associated with BCR (hazard ratio, 0.73; 95% CI, 0.57-0.93; P = .01). Although the dosiomics model outperformed the dosimetric and radiomics models, it did not outperform the clinical model. The performance significantly improved by combining the clinical variables and dosiomic features (C-index: 0.67; 95% CI, 0.65-0.68; P.0001). The predictive dosiomic features were used to distinguish high-risk and low-risk patients (P.05).The dosiomic feature extracted from the CTV was significantly correlated with BCR in patients with prostate cancer, and the dosiomics model outperformed the model with conventional dose indices. Hence, new metrics for evaluating the quality of a treatment plan are warranted. Moreover, further research should be conducted to determine whether dosiomics can be incorporated in a clinical workflow or clinical trial.

The very rapid development of ICT in the digital era has an impact on various lines of life, including changes in consumer behavior in shopping. Business people need to know the proper use of digital marketing in order to effectively target appropriate consumers. Digital marketing describes the use of technology in marketing efforts and business practices by marketing goods, services, information, and ideas via the internet, cell phones, display advertisements, and other electronic media. Data-driven marketing uncovers a variety of tactics to approach, attract, resuscitate, delight, and drive customers to online marketing. Digital marketing facilitates many-to-many communications because of the high level of connectivity and is usually used to promote products or services in a timely, relevant, more personal, and cost-effective manner. Marketing activities are carried out intensively using digital media, from promotions or product offers to product sales. Today, a website is arguably the most crucial element of your entire marketing strategy. Even a simple site without a lead capturing process or sales page will be consulted as a digital business card before a deal is struck or a purchase is made. For this reason, overhauling outdated designs to keep up with industry standards is a no-brainer. Traditional advertising is not completely dead yet. Manufacturers still use formal events like trade shows to good effect, and often spend on TV spots, magazines, and other traditional media forms. Based on the available literature, the old method of print advertising and radio ads still work but they are becoming less effective as people look to online sources for their shopping. Manufacturing companies still use these old school methods like networking events and trade shows and they still produce results. Keywords: Systematic mapping, Digital Marketing, Manufacturing, Industrial Revolution.

We describe the largest group of cave sites in Japan known to date. It includes some 50 sites, located in a gorge within the area of the modern Taishaku National Natural Park. Their characteristics are provided and their relevance to the study of the early stages of the Jomon Period is assessed. The study is based on publications, fi eld reports, and samples of artifacts owned by the museums in the Hiroshima Prefecture. The focus is on cave sites in the Chugoku region, their location, structure, inner space, and utility zones in the adjoining territory. Special attention is paid to the reconstruction of sequence in which parts of the cave space were exploited at different stages of the Jomon Period. Archaeological fi nds are described in detail—stone and bone tools, potsherds, and mollusk shells. Their analysis suggests that the Jomon people who lived in those caves subsisted mostly by hunting and freshwater mollusk collecting. Shells of marine mollusks and tools made of sanukite, which is unavailable in the area, indicate trade relations between cave dwellers and people of the adjoining regions, including the sea coast. A conclusion is made that population growth and greater reliance on hunting and fi shing territories rich in vegetation led to the change in lifestyle and subsistence strategies of the Jomon people.

Topological magnetic structure possesses topological stability characteristics that make it robust against disturbances which are a big advantage for data processing or storage devices of spintronics; nonetheless, such characteristics have been rarely clarified. This paper focused on the formation of chiral soliton lattice (CSL), a one-dimensional topological magnetic structure, and provides a discussion of its topological stability and influence of thermal fluctuation. Herein, CSL responses against change of temperature and applied magnetic field were investigated via small-angle resonant soft X-ray scattering in chromium niobium sulfide ( $$\hbox {CrNb}_3\hbox {S}_6$$ CrNb 3 S 6 ). CSL transformation relative to the applied magnetic field demonstrated a clear agreement with the theoretical prediction of the sine-Gordon model. Further, there were apparent differences in the process of chiral soliton creation and annihilation, discussed from the viewpoint of competing between thermal fluctuation and the topological metastability.

Differential phase contrast (DPC) imaging in scanning transmission electron microscopy is a technique to visualize electromagnetic field distribution inside specimens at high spatial resolution. However, diffraction contrast strongly hampers electromagnetic contrast in DPC images especially in polycrystalline samples. In this paper, we develop an imaging technique to effectively suppress diffraction contrast in DPC images. It is shown that a magnetic structure in a Nd–Fe–B permanent magnet was clearly visualized by averaging 64 DPC images with various specimen-tilt conditions. This is because the diffraction contrast in DPC images sensitively and randomly varies with crystal orientation and thus almost vanishes by averaging specimen-tilt image series. We further investigated two types of residual diffraction contrast in the tilt-series averaged DPC images: weak contrast inside grains and strong contrast at grain boundaries. We found that the former can be suppressed by averaging more DPC images, whereas the latter can be suppressed by the tilt-series averaging with wider range of specimen tilt. The tilt-series averaging method enables DPC to visualize electromagnetic structures even inside polycrystalline materials.

The objective of this study was to investigate the age difference in the response to endotoxin in calves related to the plasma endotoxin activity and mRNA expression of cytokines. Fifteen calves were divided into three groups: control (191 ± 21 days), weaning (162.4 ± 17.5 days), and calf (22.4 ± 8.2 days). The weaning and calf groups received 2.5 μg/kg of ultrapure O111:B4 LPS in 10 mL of each autologous serum, whereas the control calves received a similar volume of saline. Blood samples were collected at 0, 0.5, 1, 2, 4, 8, 12, and 24 h. Liver samples were collected by ultrasound-guided liver biopsy at 0, 2, 4, and 24 h. Plasma endotoxin activity was measured by the limulus amebocyte lysate kinetic turbidimetric assay. The mRNA expression level of GAPDH, TLR-4, NF-κB2, TNF-α, IL-6, and STAT3 in leukocytes and the liver was measured by real-time PCR. Following LPS challenge, the maximal plasma endotoxin activity, and leukocytic expression of TLR4, NF-κB2, TNF-α, and STAT3 were reached at 0.5, 4, 2-4, 2-4, and 4 h, respectively, in weaning and calf groups. The endotoxin activity in calf remained high until 2 h. Furthermore, the expression of leukocytic STAT3 mRNA in calf was not significantly different from the pre-value. In contrast, STAT3 mRNA in weaning markedly increased at 2 and 4 h. Therefore, this study provides new information to the literature of immune and inflammatory responses in calves.

This second part of the review on defects as root cause of fatigue failure comprises the origin, the nature and the effects of non-metallic inclusions. Topics addressed are the different kinds of inclusions formed during the manufacturing process, various types of mis-match causing local stresses and, as a consequence, fatigue crack initiation, and effects of characteristics such as size, morphology, localization, spatial distribution and orientation of the defects on the fatigue behavior. Methods for inclusion counting and sizing are discussed along with statistical aspects necessary to be considered when evaluating structural components.

According to the definition of the ASM handbook [ [1] , [3] ], a defect is “an imperfection … that can be shown to cause failure by a quantitative analysis and that would not have occurred in the absence of the imperfection”. The topic of the present three-part review is a discussion of defects which can cause failure in cyclically loaded structures. The features discussed comprise material defects such as non-metallic inclusions, pores or micro-shrinkages, etc. and geometric defects such as surface roughness and secondary notches which have their origin in manufacturing, and defects such as surface damage due to scratches, impact events or contact fatigue as well as corrosion pits which arise in service. In this first part, the discussion is prefaced by an introduction to basic aspects which are essential for a deeper understanding of the characteristics and mechanisms how the defects influence fatigue crack initiation and propagation. These include the life cycle of a fatigue crack from initiation up to fracture, crack arrest, multiple crack initiation and coalescence, and the material and geometrical properties affecting these.

This third part of the review on defects as root cause of fatigue failure addresses cavities (pores, micro-shrinkages, unmelted regions), defective microstructures and microcracks as material defects and defects due to local damage during manufacturing, service and maintenance such as dents, scratches and localized corrosion. In addition, damage due to contact fatigue and the effect of surface roughness are discussed in the context of fatigue failure. Also addressed is the competition between different kinds of defects in controlling the initiation and early growth of fatigue cracks.

PURPOSE/OBJECTIVE(S) Reducing radiation doses to the heart and/or cardiac segments are crucial to decrease the risk of radiation-induced coronary artery diseases (RICAD) for patients with left-sided breast cancer. However, dosimetric advantages for these structures between three-dimensional conformal radiation therapy plus electron boost (3D-CRT+EB) and simultaneous integrated boost volumetric modulated arc therapy (SIB-VMAT) remain unclear, especially in the patients with a potential risk of RICAD. The aim of this study was to compare some dosimetric parameters between the 3D-CRT + EB and SIB-VMAT in left-sided breast cancer patients with a potential risk of RICAD. MATERIALS/METHODS A total of 57 patients with left-sided breast cancer treated with SIB-VMAT between 2018 and 2020 were enrolled. All patients were identified as the potential risk of RICAD by radiation oncologists using maximum heart distance (MHD), and met the MHD ≧ 1 cm. All patients were prescribed a dose of 42.56 Gy/ 16 fractions to planning target volume and a total dose of 53.2 Gy (N = 21) or 51.2 Gy (N = 36) for a concomitant-boosted target. The 3D-CRT + EB plans were retrospectively created for a comparison purpose, using field-in-field technique followed by electron beam irradiations. Some dosimetric parameters for clinical target volume (CTV), heart, left anterior descending coronary artery (LAD), middle LAD (mLAD), lungs, and contralateral breast were compared using the Wilcoxon signed rank test. RESULTS The Dmean, Dmax and D98% for CTV were significantly improved in the SIB-VMAT plans. For cardiac-related structures, the median doses of SIB-VMAT versus 3D-CRT + EB were as follows: Dmean for heart, 2.9 Gy vs. 1.9 Gy (P < 0.001); Dmean, V20 and V30 for LAD, 12.6 Gy vs. 15.4 Gy (P < 0.001), 23.0% vs. 33.3% (P = 0.0049) and 2.0% vs. 24.7% (P < 0.001); Dmean, V20 and V30 for mLAD, 16.0 Gy vs. 21.1 Gy (P = 0.0014), 29.9% vs. 51.4% (P = 0.0040) and 0.5% vs. 31.1% (P < 0.001), respectively. The Dmean, V5 and V20 for the lungs and the Dmean for contralateral breast were significantly reduced in the 3D-CRT + EB plans (P < 0.001, for all). The doses to the LAD and mLAD tended to be higher in lateral cohort (upper outer and lower outer quadrants of breast) than in medial cohort (upper inner and lower inner quadrants of breast), while these doses were significantly reduced by the SIB-VMAT. CONCLUSION Although 3D-CRT + EB technique can reduce the mean dose to the heart, the doses to LAD and mLAD can be significantly decreased by SIB-VMAT, which could be a benchmark for selecting the most appropriate irradiation technique in the patients with a potential risk of RICAD.

This review summarizes investigations carried out at the Laboratory of Photochemistry and Energy Conversion (LFCE) in the University of São Paulo dealing with design and characterization of ruthenium(II), rhenium(I) and iridium(III) polypyridine complexes with desired photochemical and photophysical properties in light of the development of optoelectronics and photoinduced energy conversion systems. First, the breakthroughs on molecular engineering of emissive ReI, RuII and IrIII complexes for the development of highly efficient light-emitting devices, such as organic light-emitting diodes (OLEDs) and light-emitting electrochemical cells (LECs), are presented. Then, the photochemical and photophysical properties of fac-[Re(CO)3(NN)(trans-L)]+ complexes (NN = bidentate polypyridyl ligands and trans-L = stilbene-like ligand), which find use in molecular machines and photosensors, are discussed. Finally, dye-sensitized energy conversion devices based on RuII complexes and natural dyes, such as dye-sensitized solar cells (DSCs) and dye-sensitized photoelectrosynthesis cells (DSPECs), are reviewed, highlighting some strategies for photoanode engineering aiming at improved device efficiencies.

Vancomycin is associated with nephrotoxicity; however, the influence of the number of combined nephrotoxic agents on the incidence of vancomycin nephrotoxicity has not been clarified. We investigated patient backgrounds in 148 inpatients who received vancomycin treatment. The patients were divided into nephrotoxicity (n=35) and non-nephrotoxicity (n=113) groups. A comparison of the patient backgrounds in the two groups revealed significant differences in weight, changes in serum creatinine before vancomycin administration, blood urea nitrogen to serum creatinine ratio, length of vancomycin therapy, vancomycin trough concentration, and number of combined nephrotoxic agents. Multiple logistic regression analysis using these six factors as autonomous variables showed that the highest vancomycin trough concentration (odds ratio, 1.080; 95% confidence interval, 1.030-1.140; p = 0.003) and the number of combined nephrotoxic agents (odds ratio, 1.590; 95% confidence interval, 1.120-2.260; p = 0.010) were significantly related to nephrotoxicity.

Topological magnetic structure possesses topological stability characteristics that make it robust against disturbances which are a big advantage for data processing or storage devices of spintronics; nonetheless, such characteristics have been rarely clarified. This paper focused on the formation of chiral soliton lattice (CSL), a one-dimensional topological magnetic structure, and provides a discussion of its topological stability and influence of thermal fluctuation. Herein, CSL responses against change of temperature and applied magnetic field were investigated via small-angle resonant soft X-ray scattering in chromium niobium sulfide (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\hbox {CrNb}_3\hbox {S}_6$$\end{document}CrNb3S6). CSL transformation relative to the applied magnetic field demonstrated a clear agreement with the theoretical prediction of the sine-Gordon model. Further, there were apparent differences in the process of chiral soliton creation and annihilation, discussed from the viewpoint of competing between thermal fluctuation and the topological metastability.

PURPOSE The aperture shape controller (ASC) decreases the complexity of the multi-leaf collimator (MLC) aperture for volumetric modulated arc therapy (VMAT). The purpose of this study was to evaluate the effect of ASC settings on the VMAT plan quality. METHOD First, VMAT plans were created (ASC=off) for three test patterns of The American Association of Physicists in Medicine (AAPM) Task Group 119 (TG-119) and 20 cases of nasopharyngeal cancer. Next, for these VMAT plans, only the ASC settings were changed from very low (complexity reduction: low) to very high (complexity reduction: high) in five steps, and VMAT plans were created respectively. To evaluate the created VMAT plans per each ASC settings, we analyzed the modulation complexity score (MCSV) and dosimetric parameters for the planning target volume (PTV) and organ at risk (OAR). RESULT In three test patterns, there were no major dosimetric differences between the VMAT plans. In nasopharyngeal cancer, the mean MCSV were 0.413, 0.325, 0.320, 0.307, 0.303, and 0.272 for very high, high, moderate, low, very low, off settings, respectively. Therefore, the most complex MLC aperture was off, followed by very low, low, moderate, high, and very high. In terms of dosimetric parameters, the VMAT plans created using the very high setting showed an increase of D2% in the PTV and worse OAR sparing than that using other ASC settings. On the other hand, the dosimetric results for the very low to moderate setting obtained similar results to those for the off setting, respectively. CONCLUSION The ASC was able to decrease the complexity of the MLC aperture according to the setting level. From very low to moderate settings, a plan equivalent to the off setting could be created in terms of dose parameters.

Background Intraperitoneal chemotherapy using paclitaxel is considered an experimental approach for treating peritoneal carcinomatosis. This study aimed to determine the recommended dose, and to evaluate the clinical efficacy and safety, of the combination of intravenous gemcitabine, intravenous nab‐paclitaxel and intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis. Methods The frequencies of dose‐limiting toxicities were evaluated, and the recommended dose was determined in phase I. The primary endpoint of the phase II analysis was overall survival rate at 1 year. Secondary endpoints were antitumour effects, symptom‐relieving effects, safety and overall survival. Results The recommended doses of intravenous gemcitabine, intravenous nab‐paclitaxel and intraperitoneal paclitaxel were 800, 75 and 20 mg/m2 respectively. Among 46 patients enrolled in phase II, the median time to treatment failure was 6·0 (range 0–22·6) months. The response and disease control rates were 21 of 43 and 41 of 43 respectively. Ascites disappeared in 12 of 30 patients, and cytology became negative in 18 of 46. The median survival time was 14·5 months, and the 1‐year overall survival rate was 61 per cent. Conversion surgery was performed in eight of 46 patients, and those who underwent resection survived significantly longer than those who were not treated surgically (median survival not reached versus 12·4 months). Grade 3–4 haematological toxicities developed in 35 of 46 patients, whereas non‐haematological adverse events occurred in seven patients. Conclusion Adding intraperitoneal paclitaxel had clinical efficacy with acceptable tolerability., This multicentre phase I/II study was undertaken to determine the recommended dose of the combination of intravenous gemcitabine, intravenous nab‐paclitaxel and intraperitoneal paclitaxel in patients with pancreatic ductal adenocarcinoma and peritoneal metastasis, and to evaluate its clinical efficacy and safety. This regimen exhibited promising clinical efficacy, with acceptable tolerability. Effective and safe in pancreatic cancer

Background Although some retrospective studies have suggested the value of adjuvant therapy, no recommended standard exists in bile duct cancer. The aim of this study was to test the hypothesis that adjuvant gemcitabine chemotherapy would improve survival probability in resected bile duct cancer. Methods This was a randomized phase III trial. Patients with resected bile duct cancer were assigned randomly to gemcitabine and observation groups, which were balanced with respect to lymph node status, residual tumour status and tumour location. Gemcitabine was given intravenously at a dose of 1000 mg/m2, administered on days 1, 8 and 15 every 4 weeks for six cycles. The primary endpoint was overall survival, and secondary endpoints were relapse-free survival, subgroup analysis and toxicity. Results Some 225 patients were included (117 gemcitabine, 108 observation). Baseline characteristics were well balanced between the gemcitabine and observation groups. There were no significant differences in overall survival (median 62·3 versus 63·8 months respectively; hazard ratio 1·01, 95 per cent c.i. 0·70 to 1·45; P = 0·964) and relapse-free survival (median 36·0 versus 39·9 months; hazard ratio 0·93, 0·66 to 1·32; P = 0·693). There were no survival differences between the two groups in subsets stratified by lymph node status and margin status. Although haematological toxicity occurred frequently in the gemcitabine group, most toxicities were transient, and grade 3/4 non-haematological toxicity was rare. Conclusion The survival probability in patients with resected bile duct cancer was not significantly different between the gemcitabine adjuvant chemotherapy group and the observation group. Registration number: UMIN 000000820 (http://www.umin.ac.jp/).

PURPOSE/OBJECTIVE(S) Radiotherapy is one of the main treatment strategies for localized prostate cancer. Although several patients receive external radiotherapy, the relationships between dosimetric factors related to the treatment planning and biochemical recurrence (BCR) remain unclear. The aims of the present study were to develop a prediction model for BCR by integrating dose-based radiomics (dosiomics) features and clinical variables in prostate cancer patients, and to clarify the relationships between the dosimetric factors and BCR. MATERIALS/METHODS A total of 489 patients with adenocarcinoma of the prostate who had been prescribed a dose of 78 Gy in 39 fractions with intensity modulated radiation therapy from 2007 to 2014 were retrospectively enrolled. A total of 2,475 dosiomic features were calculated from the 3D doses in prostate, clinical target volume (CTV), and planning target volume (PTV), and relevant 8 clinical variables for BCR were also considered. Feature selection was performed to eliminate redundant or not significant features. Multivariate cox proportional hazards regression model was trained on the training cohort of 342 patients using the selected features, and the predictive performance was validated on the validation cohort of 147 patients using the concordance index (C-index). Kaplan-Meir curves with log-rank analysis was used to assess the univariate discrimination of freedom from biochemical failure (FFBF) between high- and low-risk BCR groups. RESULTS A total of 96 patients developed BCR with the median time of 55.2 months. Two dosiomic features (1 from CTV and 1 from PTV) and three clinical variables were selected as predictive factors. Of the five, CTV (HGLRE) (hazard ratio [HR]: 0.73; 95% confidence intervals [CI]: 0.57-0.93; P = 0.01), pretreatment prostate-specific antigen (HR: 1.27; 95% CI: 1.04-1.55; P = 0.02) and positive biopsy core rate (HR: 1.40; 95% CI: 1.07-1.82; P = 0.01), were significantly associated with BCR. The C-index of the model in the validation cohort was 0.67 (95% CI: 0.65-0.68). CTV_wavelet-HHH_glrlm_HGLRE could significantly distinguish the patients into high- and low-risk groups (8-year FFBF: 76.6% vs. 87.5%, P < 0.01). CONCLUSION The dosiomic feature extracted from CTV can be a relevant predictive factor for BCR after radiotherapy in prostate cancer patients and may be useful as new metric for evaluating the quality of a treatment plan, instead of conventional dose indices.