In this paper, a chain of scientific tools is applied to provide a flexible, efficient, and extensible toolchain that is capable of addressing limitations in corrosion simulation. A previously ...developed computational model of galvanic corrosion for Magnesium–Aluminium couples is considered and the necessities on the choice of implementation strategy is presented. Within this context the suitability of a novel approach, based on a recent developed algebraic flux correction method, is discussed. This suitability is argued in two directions. First, the agreement of the finite element theory with the characteristics of the problem. Second, the advantage of the method and the benefits gained by utilizing the implementation strategy. It is shown that the composition of the tools, and the finite element method successfully captures the expected model results and pose a good trade-off between simplicity, flexibility, and efficiency for a wider range of models.
•Simulating complex corrosion models yields many challenges in the implementation process.•A resource consuming part of corrosion simulation is to solve the Poisson–Nernst–Planck (PNP) model.•The choice of the finite element method and an implementation tool facilitates solving the PNP model.•The developed toolchain in this work tackles the simulation challenges and speeds it up by the employed implementation strategy.
The clinical presentations of early idiopathic Parkinson disease (IPD) substantially overlap with those of atypical parkinsonian syndromes such as multiple system atrophy (MSA) and progressive ...supranuclear palsy (PSP). This study aimed to develop metabolic imaging indices based on deep learning to support the differential diagnosis of these conditions.
A benchmark Huashan parkinsonian PET imaging (HPPI, China) database including 1,275 parkinsonian patients and 863 nonparkinsonian subjects with
F-FDG PET images was established to support artificial intelligence development. A 3-dimensional deep convolutional neural network was developed to extract deep metabolic imaging (DMI) indices and blindly evaluated in an independent cohort with longitudinal follow-up from the HPPI and an external German cohort of 90 parkinsonian patients with different imaging acquisition protocols.
The proposed DMI indices had less ambiguity space in the differential diagnosis. They achieved sensitivities of 98.1%, 88.5%, and 84.5%, and specificities of 90.0%, 99.2%, and 97.8%, respectively, for the diagnosis of IPD, MSA, and PSP in the blind-test cohort. In the German cohort, they resulted in sensitivities of 94.1%, 82.4%, and 82.1%, and specificities of 84.0%, 99.9%, and 94.1%, respectively. Using the PET scans independently achieved a performance comparable to the integration of demographic and clinical information into the DMI indices.
The DMI indices developed on the HPPI database show the potential to provide an early and accurate differential diagnosis for parkinsonism and are robust when dealing with discrepancies between populations and imaging acquisitions.
To develop guidelines for performing and interpreting positron emission tomography (PET) imaging for treatment assessment in patients with lymphoma both in clinical practice and in clinical trials.
...An International Harmonization Project (IHP) was convened to discuss standardization of clinical trial parameters in lymphoma. An imaging subcommittee developed consensus recommendations based on published PET literature and the collective expertise of its members in the use of PET in lymphoma. Only recommendations subsequently endorsed by all IHP subcommittees were adopted.
PET after completion of therapy should be performed at least 3 weeks, and preferably at 6 to 8 weeks, after chemotherapy or chemoimmunotherapy, and 8 to 12 weeks after radiation or chemoradiotherapy. Visual assessment alone is adequate for interpreting PET findings as positive or negative when assessing response after completion of therapy. Mediastinal blood pool activity is recommended as the reference background activity to define PET positivity for a residual mass > or = 2 cm in greatest transverse diameter, regardless of its location. A smaller residual mass or a normal sized lymph node (ie, < or = 1 x 1 cm in diameter) should be considered positive if its activity is above that of the surrounding background. Specific criteria for defining PET positivity in the liver, spleen, lung, and bone marrow are also proposed. Use of attenuation-corrected PET is strongly encouraged. Use of PET for treatment monitoring during a course of therapy should only be done in a clinical trial or as part of a prospective registry.
In patients with cancer who have an abnormal biomarker finding, the source of the biomarker in the bloodstream must be located for confirmation of diagnosis, staging, and therapy planning. We ...evaluated if immuno-PET with the radiolabeled high-affinity antibody HuMab-5B1 (MVT-2163), binding to the cancer antigen CA19-9, can identify the source of elevated biomarkers in patients with pancreatic cancer.
In this phase I dose-escalating study, 12 patients with CA19-9-positive metastatic malignancies were injected with MVT-2163. Within 7 days, all patients underwent a total of four whole-body PET/CT scans. A diagnostic CT scan was performed prior to injection of MVT-2163 to correlate findings on MVT-2163 PET/CT.
Immuno-PET with MVT-2163 was safe and visualized known primary tumors and metastases with high contrast. In addition, radiotracer uptake was not only observed in metastases known from conventional CT, but also seen in subcentimeter lymph nodes located in typical metastatic sites of pancreatic cancer, which were not abnormal on routine clinical imaging studies. A significant fraction of the patients demonstrated very high and, over time, increased uptake of MVT-2163 in tumor tissue, suggesting that HuMab-5B1 labeled with beta-emitting radioisotopes may have the potential to deliver therapeutic doses of radiation to cancer cells.
Our study shows that the tumor antigen CA19-9 secreted to the circulation can be used for sensitive detection of primary tumors and metastatic disease by immuno-PET. This significantly broadens the number of molecular targets that can be used for PET imaging and offers new opportunities for noninvasive characterization of tumors in patients.
Radioiodide (RAI) therapy of thyroid cancer exploits the relatively selective ability of thyroid cells to transport and accumulate iodide. Iodide uptake requires expression of critical genes that are ...involved in various steps of thyroid hormone biosynthesis. ERK signaling, which is markedly increased in thyroid cancer cells driven by oncogenic BRAF, represses the genetic program that enables iodide transport. Here, we determined that a critical threshold for inhibition of MAPK signaling is required to optimally restore expression of thyroid differentiation genes in thyroid cells and in mice with BrafV600E-induced thyroid cancer. Although the MEK inhibitor selumetinib transiently inhibited ERK signaling, which subsequently rebounded, the MEK inhibitor CKI suppressed ERK signaling in a sustained manner by preventing RAF reactivation. A small increase in ERK inhibition markedly increased the expression of thyroid differentiation genes, increased iodide accumulation in cancer cells, and thereby improved responses to RAI therapy. Only a short exposure to the drug was necessary to obtain a maximal response to RAI. These data suggest that potent inhibition of ERK signaling is required to adequately induce iodide uptake and indicate that this is a promising strategy for the treatment of BRAF-mutant thyroid cancer.
Luthers Erben der dritten Generation, die Pastoren des 17. Jahrhunderts, sicherten die Reformation in einer Epoche des Krieges, der Krisen und Umbrüche. Dennoch stehen sie bis heute im Schatten ihres ...großen Vorgängers. Wie sahen sie sich selbst, was befähigte sie zu ihrer Leistung, und welche Anpassungen an ihre Welt nahmen sie vor? Erst die Kenntnis dieser ebenso faszinierenden wie ernüchternden Vorgänge macht die Entwicklung des Luthertums bis zur Gegenwart verständlich.
A previous study suggested that measurement of therapy-induced changes in tumor glucose metabolism by positron emission tomography (PET) with the glucose analog 18Ffluorodeoxyglucose (FDG) allows to ...select patients most likely to benefit from preoperative chemotherapy in adenocarcinomas of the esophagogastric junction (AEG). The aim of this study was to prospectively validate these findings by using an a priori definition of metabolic response.
Sixty-five patients with locally advanced AEGs were included. Tumor glucose utilization was quantitatively assessed by FDG-PET before chemotherapy and 14 days after initiation of therapy. Patients were classified as metabolic responders when the metabolic activity of the primary tumor had decreased by more than 35% at the time of the second PET.
Metabolic responders showed a high histopathologic response rate (44%) with a 3-year survival rate of 70%. In contrast, prognosis was poor for metabolic nonresponders with a histopathologic response rate of 5% (P = .001) and a 3-year survival rate of 35% (P = .01). A multivariate analysis (covariates: ypT-, ypN-category, histopathologic response) demonstrated that metabolic response was the only factor predicting recurrence (P = .018) in the subgroup of completely resected (R0) patients.
This study prospectively demonstrates that changes in tumor metabolic activity during chemotherapy predict response, prognosis, and recurrence. These data provide the basis for clinical trials in which preoperative treatment is changed for patients without a metabolic response early in the course of therapy. PET-guided induction therapy may even be applicable to earlier tumor stages because surgery is only minimally delayed in nonresponding patients.
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