Cytokeratin 5 (CK5) is a marker for pulmonary squamous cell carcinoma; however, CK5 is sometimes present in pulmonary adenocarcinoma (ADC), and there is insufficient information regarding the ...clinicopathological features of CK5‐positive ADC. We aimed to explore the clinicopathological characteristics of CK5‐positive ADC using immunohistochemistry. We prepared the following two cohorts: a resected cohort containing 220 resected tumours for primarily studying the detailed morphological characteristics, and a tissue microarray (TMA) cohort containing 337 samples for investigating the associations of CK5 expression with other protein expressions, genetic and prognostic findings. CK5‐positive ADC was defined to have ≥ 10% tumour cells and presence of CK5‐positive tumour cells in the resected and TMA cohorts, respectively. CK5‐positive ADCs were identified in 91 (16.3%) patients in the combined cohort. CK5‐positive ADCs had male predominance (P = 0.012), smoking history (P = 0.001), higher stage (P < 0.001), histological high‐grade components (P < 0.001), vascular invasion (P < 0.001), mucinous differentiation (P < 0.001), spread through airspaces (P < 0.001), EGFR wild‐type (P < 0.001), KRAS mutations (P < 0.001), ALK rearrangement (P < 0.001) and ROS1 rearrangement (P = 0.002). In the resected cohort, more than half the CK5‐positive ADCs (19 cases, 65.5%) showed mucinous differentiation; the remaining cases harboured high‐grade components. In the TMA cohort, CK5‐positive ADCs correlated with TTF‐1 negativity (P = 0.002) and MUC5B, MUC5AC and HNF4alpha positivity (P < 0.001, 0.048, < 0.001). Further, CK5‐positive ADCs had significantly lower disease‐free and overall survival rates than CK5‐negative ADCs (P < 0.001 for each). Additionally, multivariate analysis revealed that CK5 expression was an independent poor prognostic factor. CK5‐positive ADCs showed aggressive clinical behaviour, with high‐grade morphology and mucinous differentiation.
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The Thermodynamics of Advanced Fuels – International Database (TAF-ID) was developed using the Calphad method to provide a computational tool to perform thermodynamic calculations on nuclear fuel ...materials under normal and off-normal conditions. Different kinds of fuels are considered: oxide, metallic, carbide and nitride fuels. Many fission products are introduced as well as structural materials (e.g., zirconium, steel, concrete, SiC) and absorbers (e.g., B4C), in order to investigate the thermochemistry of irradiated fuels and to predict their chemical interaction with the surrounding materials. The approach to develop the database and the models implemented in the database are described. Examples of models for key chemical systems are presented. Finally, a few examples of application calculations on severe accidents with UO2 fuels, irradiated fuel chemistry of MOX and metallic fuels and metallic fuel/cladding interaction show how this tool can be used. To validate the database, the calculations are compared to the available experimental data. A good agreement is obtained which gives confidence in the maturity degree and quality of the TAF-ID database. The working version is only accessible to the participants of the TAF-ID project (Canada, France, Japan, the Netherlands, Republic of Korea, United Kingdom, USA). A public version is accessible by all the NEA countries. The current version contains models on the Am–Fe, Am–Np, Am-O-Pu, Am–U, Am–Zr, C–O–U-Pu, Cr–U, Np–U, Np–Zr, O–U–Zr, Re–U, Ru–U, Si–U, Ti–U, U-Pu-Zr, U–W systems. It is progressively extended with our published assessments. Information on how to join the project is available on the website: https://www.oecd-nea.org/science/taf-id/.
•The TAF-ID international thermodynamic database is a computational tool for nuclear fuel applications.•Key systems for nuclear fuels are modelled using the Calphad method.•Fission product chemistry of irradiated fuels is predicted.•Chemical interaction with structural materials can be predicted under normal and severe accident conditions.•Coupling with kinetics, phase-field, Fuel Performance Code is being performed.
In order to understand the stratification process that may occur in the late phase of the fuel degradation during a severe accident in a PWR, the thermodynamic knowledge of the U-Zr-O system is ...crucial. The presence of a miscibility gap in the U-Zr-O liquid phase may lead to a stratified configuration, which will impact the accidental scenario management. The aim of this work was to obtain new experimental data in the U-Zr-O liquid miscibility gap. New tie-line data were provided at 2567 ± 25 K. The related thermodynamic models were reassessed using present data and literature values. The reassessed model will be implemented in the TAF-ID international database. The composition and density of phases potentially formed during stratification will be predicted by coupling current thermodynamic model with thermal-hydraulics codes.
•We obtained experimental results on the U-Zr-O liquid miscibility gap.•Two tie-lines in the miscibility gap have been obtained, showing that liquid immiscibility already exists at 2567 ± 25 K.•The thermodynamic models of the binary U-Zr and ternary U-Zr-O systems has been reassessed.•Thermodynamic calculation have been performed to interpret current experimental results.
Interaction tests between UO
2
and Zr were performed at precisely controlled high temperatures between 1840 and 2000°C (±2.5°C for 1900, 1920, 1930, 1940, and 2000°C, ±10°C for 1840 and 1890°C, ...respectively), to understand the interaction mechanism in detail. A Zr rod was inserted in a UO
2
crucible and then heat-treated at a fixed temperature in an Ar-gas flow for 10 min. After heating in the range of 1890 to 1930°C, the Zr rod was deformed to a round shape, in which the post-analysis detected the significant diffusion of U into the Zr region and the formation of a dominant α-Zr(O) matrix and a small amount of U-Zr-O precipitates. An abrupt process of liquefaction was observed in the sample heated at around 1940°C or higher. Furthermore, the post-analysis results suggested the detailed liquefaction mechanism: (1) the higher oxygen concentration in the α-Zr(O) matrix suppressed the liquefaction progress, due to the variation in the equilibrium state; (2) the U-Zr-O melt formation progressed by the selective dissolution of Zr from the matrix, corresponding to the reverse variation of the oxygen concentration in the matrix; (3) the selective diffusion of U could occur via the U-Zr-O melt.
Background
The aim of this study was to determine the added value of portal or superior mesenteric vein (PV/SMV) resection during pancreatoduodenectomy for pancreatic head carcinoma.
Methods
A ...multicentre observational study was conducted in patients with pancreatic head carcinoma who underwent pancreatoduodenectomy in seven Japanese hospitals between 2001 and 2012. Clinicopathological factors were compared between patients who did and did not undergo PV/SMV resection. Those with an impact on survival were identified by univariable and multivariable analysis.
Results
Of the 937 patients who underwent pancreatoduodenectomy, 435 (46·4 per cent) had PV/SMV resection, whereas the remaining 502 (53·6 per cent) did not. Some 71·5 and 63·9 per cent of patients with and without PV/SMV resection respectively had lymph node‐positive disease. Patients who underwent PV/SMV resection had more advanced tumours. Perioperative mortality and morbidity rates did not differ between the two groups. Multivariable analysis revealed that PV/SMV resection was not an independent prognostic factor for overall survival (P = 0·268). Among the 435 patients in whom the PV/SMV was resected, borderline resectable tumours with arterial abutment (P = 0·021) and absence of adjuvant chemotherapy (P < 0·001) were independent predictors of poor survival in multivariable analysis. Patients with resectable or borderline resectable tumours with PV/SMV involvement had a median survival time with additional adjuvant chemotherapy of 43·7 and 29·7 months respectively. Median survival time in patients with borderline resectable tumours with arterial abutment was 18·6 months despite adjuvant chemotherapy.
Conclusion
Pancreatoduodenectomy with PV/SMV resection and adjuvant chemotherapy in patients with pancreatic head carcinoma may provide good survival without increased mortality and morbidity.
Potential role for adjuvant chemotherapy
Summary
Background
Although infectious agents have long been implicated in the induction or exacerbation of pemphigus vulgaris (PV), a convincing role for the agent in the aetiology of PV has not ...been established.
Objectives
To establish the association with PV and herpes simplex virus (HSV).
Patients and methods
We examined saliva for the presence of HSV DNA after the onset of PV initially localized to the oral lesions in addition to conventional serological tests and immunohistochemistry.
Results
We successfully detected high levels of HSV DNA in the saliva samples from six of 16 patients with PV at the earliest stage, who had no episodes of herpes simplex. The prevalence (37·5%) of detecting HSV DNA in the patients with PV was lower than that of eczema herpeticum (56·5%), but comparable to that in patients with herpes labialis (30·0%). Copy numbers of the HSV DNA were rather higher than those with herpes labialis and with eczema herpeticum. In general, detection of HSV DNA in saliva was transient and restricted to the earliest phase of the disease. In addition, anti‐HSV immunoglobulin (Ig) G titres in patients with PV were significantly higher than those in patients with virologically confirmed HSV‐induced disorders. All salivary HSV DNA‐positive patients with PV had run a more complex, intractable course refractory to conventional therapy.
Conclusions
Detection of HSV DNA in saliva is a useful and noninvasive, quantitative method for establishing the role of HSV in the pathogenesis of PV and for identifying individuals at greater risk for subsequently developing refractory PV.
What's already known about this topic?
Although infectious agents have long been implicated in the induction or exacerbation of pemphigus vulgaris (PV), a convincing role for the agent in the aetiology of PV has not been established.
What does this study add?
We successfully detected high levels of herpes simplex virus (HSV) DNA in the saliva samples from six of 16 patients with PV at the earliest stage, who had no episodes of herpes simplex.
These patients with PV have run a more complex, intractable course refractory to conventional therapy.
Detection of HSV DNA in saliva will alert physicians to the possibility of greater risk of subsequently developing refractory PV.
To evaluate the usefulness of synthetic magnetic resonance imaging (MRI) performed before the initiation of neoadjuvant chemotherapy (NAC) in predicting whether breast cancers can achieve a ...pathological complete response (pCR) after the completion of NAC.
This retrospective study investigated 37 consecutive patients with 39 breast cancers (pCR: 14, and non-pCR: 25) who underwent dynamic contrast-enhanced (DCE)-MRI and synthetic MRI before the initiation of NAC. Using synthetic MRI images, quantitative values (T1 and T2 relaxation times, proton density PD and their standard deviations SD) were obtained in breast lesions, before (Pre-T1, Pre-T2, Pre-PD, SD of Pre-T1, SD of Pre-T2, SD of Pre-PD) and after (Gd-T1, Gd-T2, Gd-PD, SD of Gd-T1, SD of Gd-T2, SD of Gd-PD) contrast agent injection. The aforementioned quantitative values and several morphological features that were identified on DCE-MRI were compared between pCR and non-pCR.
Multivariate analyses revealed that the SD of Pre-T2 (p=0.038) was significant and was an independent predictor of pCR, with an area under the receiver operating characteristics curve of 0.829. The sensitivity, specificity, and accuracy of the SD of Pre-T2 with an optimal cut-off value of 11.5 were 71.4%, 80%, and 76.3%, respectively.
The SD of Pre-T2 obtained from synthetic MRI was used successfully to predict those breast cancers that would achieve a pCR after the completion of NAC; however, these results are preliminary and need to be verified by further studies.
•Accurately predicting tumour response to NAC in breast cancer is crucial.•Synthetic MRI can obtain some quantitative values during a single scan.•SD of T2-Pre of breast cancer was successfully used to predict pCR prior to NAC.
Background
Neoadjuvant chemotherapy (NAC) represents a promising alternative to pancreatic ductal adenocarcinoma (PDAC) planned resection, but the survival impact remains undefined. To assess the ...feasibility and survival outcomes of NAC with gemcitabine and S1 (GS) for PDAC planned resection by prospective study.
Methods
Patients with resectable or borderline resectable PDAC received 2 cycles of NAC-GS and were offered curative resection followed by gemcitabine adjuvant. The primary endpoint was 2-year overall survival (OS). Adverse events during NAC, radiological and tumor marker responses, resection rate, and surgical safety were evaluated as secondary endpoints (UMIN000004148).
Results
We enrolled 104 patients between 2010 and 2012, with 101 patients treated using NAC-GS as the full analysis set (FAS). Of the 101 patients, 88% received the planned 2 cycles of NAC. Grade 3 neutropenia was common (35%). Radiological partial response and decreased carbohydrate antigen 19-9 concentration (> 50% decrease) were noted in 13% and 41%, respectively. R0/1 resections with M0 were performed in 65 patients without surgical mortality. Of the 65 patients, 44 received planned gemcitabine adjuvant for 6 months as the on-protocol cohort. The primary endpoint for the 2-year OS rate was 55.9% in the FAS (
n
= 101) and 74.6% in the on-protocol cohort (
n
= 44).
Conclusions
NAC-GS was feasible and actively prolonged survival following PDAC planned resection. Randomized control trials are needed to further clarify the survival benefit of NAC-GS in addition to surgery followed by adjuvant therapy.
In a severe accident, a rapid temperature increase leads to thinning of the ZrO2 layer and the both of the UO2 dissolution by molten Zr, and relocation could take place within very short period. This ...paper considered such situation and proposed the relocation condition of “the quick dissolution scenario” with the melt composition at relocating temperature under a quasi-equilibrium assumption. The calculated values were compared with the UO2 solubility observed in the UO2–Zr dissolution tests representing “the slow dissolution scenario” in which the melt is held for a while by the ZrO2 layer. Two phases were recognized in the experiments with latter scenario: ceramic (U,Zr)O2−x phase and metallic liquid phase. The melt composition in each scenario was also converted from the U–Zr–O system to the UO2–ZrO2–Zr system as an example of user-defined criteria of dissolution which can be applied to the severe accident code analysis. The difference between two scenarios (“quick” and “slow”) can result in differing times of lower head failure through the high liquidus temperature of oxide solid phase or chemical activity of metallic liquid phase. Providing the conditions for different mechanisms in the consistent manner for the thermodynamic analysis enabled evaluation of the fuel dissolution behavior in the context of integral accident progression.
AbstractDense networks of low-cost wireless sensors have the potential to facilitate prolific data collection in large and complex infrastructure at costs lower than those historically associated ...with tethered counterparts. While wireless telemetry has been previously proposed for structural monitoring, comparatively less research has focused on the creation of a complete and scalable data management system that manages the storage and interrogation of wireless sensor data. This paper reports on the development of a novel wireless structural monitoring system specifically tailored for large-scale civil infrastructure systems by architecturally combining dense wireless sensor networks with a suite of information technologies remotely accessible by the Internet. The architectural overview of the proposed Internet-enabled wireless structural monitoring system is presented including a description of its functional elements (for example, wireless sensors, database server, and application programming interfaces). The monitoring-system architecture proposed is validated on the New Carquinez (Alfred Zampa Memorial) Bridge in Vallejo, California. A permanent wireless monitoring system is installed consisting of 28 wireless sensor nodes collecting data from over 80 channels. The bridge sensor data are transferred by a wireless cellular connection to a remote database server where it is stored and available for interrogation by software clients granted access to the data. To illustrate the ability to autonomously process the bridge response data, the stochastic subspace identification method is used to extract accurate modal characteristics of the bridge that are used to update high-fidelity finite-element models of the bridge. The Internet-enabled wireless structural monitoring system proved to be scalable to a large number of nodes and has thus far proven stable and reliable over long-term use.
