Simulating Elastoplastic and Anisotropic Behavior in Thermoplastic Additively Manufactured Components: An Application-Oriented Modeling Approach.

This paper presents a comprehensive approach aimed at developing a coupled process-structure simulation that integrates anisotropic and elastoplastic material behavior for plastic components manufactured through Fused Filament Fabrication (FFF) 3D printing. The simulation incorporates material orientation considerations, linking the process simulation with structural simulation. Subsequently, stress and strain values from the simulations are compared with the test results. Moreover, the fracture behavior of components manufactured in this way is also taken into account in relation to material orientation. The executed simulations have yielded successful outcomes, affirming the efficacy of the anisotropic and elastoplastic simulation across all strand orientations. Special attention is paid to the application of the method. Here, the simulation method introduced in this contribution with the approaches for describing the material behavior under mechanical load can be used in the future in the dimensioning of FFF manufactured plastic components to predict the deformation behavior and failure, especially under consideration of a well economic and efficient virtual product development.

Impact of the Localization of the Primary Tumor and RAS/BRAF Mutational Status on Maintenance Strategies After First-line Oxaliplatin, Fluoropyrimidine, and Bevacizumab in Metastatic Colorectal Cancer: Results From the AIO 0207 Trial.

INTRODUCTION: Numerous trials have examined the prognostic and predictive value of localization of the primary tumor (LPT) in metastastic colorectal cancer, there is limited information about the predictive value of LPT on different maintenance strategies. MATERIALS AND METHODS: We analyzed progression-free survival (PFS)/overall survival (OS) on maintenance therapy according to LPT and mutational subgroups (BRAF/RAS) in patients from the AIO (Arbeitsgemeinschaft Internistische Onkologie) 0207 trial. Following induction, 471 patients were randomized to fluoropyrimidine (FU)/bevacizumab (Bev), Bev, or no treatment. Data on LPT were available in 414 (91%) patients. RESULTS: A total of 291 patients were left-sided (LPTl, 70%), and 123 were right-sided (LPTr, 30%). The median PFS was 3.9 months for LPTr and 5.3 months for LPTl (P = .11; hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.96-1.48). There was no predictive impact of LPT on the maintenance strategies. The pairwise comparison of treatment arms showed a better PFS for FU/Bev versus no treatment independent from LPT (left, P < .0001; HR, 2.39; 95% CI, 1.73-3.31; right, P = .011; HR, 1.78; 95% CI, 1.14-2.80). Analysis for OS (429 patients) confirmed the strong prognostic impact of LPT (left vs. right: 24.0 vs. 16.7 months; P < .0001; HR, 1.65; 95% CI, 1.32-2.06), but also without major interaction between the LPT and maintenance arms. The strong negative prognostic impact of BRAF mutation was confirmed in right-/left-sided metastastic colorectal cancer, reaching significance in LPTl. In patients with RAS mutational status, the negative prognostic impact of the mutation remains, but its effect is stronger in LPTl (P < .0001). CONCLUSION: The strong prognostic factor of LPT is confirmed undergoing oxaliplatin/FU/Bev induction therapy, whereas there seems to be no major predictive impact of LPT on different maintenance strategies.

Impact of primary tumour location and RAS/BRAF mutational status in metastatic colorectal cancer treated with first-line regimens containing oxaliplatin and bevacizumab: Prognostic factors from the AIO KRK0207 first-line and maintenance therapy trial.

BACKGROUND: The major prognostic relevance of primary tumour location (LPT) in advanced colorectal cancer was shown in large retrospective studies, but quantitative estimates are highly heterogeneous, and there is still limited information about its impact within the framework of biomarker-guided treatment strategies. Therefore, we analysed LPT in relation to other clinical and molecular parameters, based on mature survival data from the recent randomised AIO KRK0207 trial. METHODS: Patients uniformly received first-line induction treatment with a combination of bevacizumab, oxaliplatin and fluoropyrimidine. LPT was retrospectively determined using surgical reports, pathology reports and endoscopy reports. The prognostic analyses were performed using Kaplan-Meier estimations and log-rank tests, while hazard ratios (HRs) and multivariable results were derived from Cox models. RESULTS: Among 754 patients with unequivocal information on LPT, patients with left-sided tumours showed a median overall survival of 24.8 months compared with the right-sided cohort with 18.4 months (HR: 1.54, 95% confidence interval: 1.30-1.81, P < 0.0001). In a multivariable model, LPT proved to be the strongest prognosticator (HR 1.60), with performance status, number of metastatic sites, baseline carcinoembryonic antigen (CEA) and platelets independently retaining prognostic significance. In the subgroup of patients with known RAS/BRAF status (n = 567, 75%), a BRAF mutation showed the greatest unfavourable impact (HR 3.16). Although BRAF is strongly correlated to LPT, the latter remained a significant prognosticator in the BRAF wild-type subgroup. In contrast, no major impact of LPT was seen on tumours carrying RAS mutations. CONCLUSIONS: Within the framework of a uniform treatment strategy according to the current standards, LPT proved to have an important, although not solely dominating, relevance for survival prognosis. Its impact seems to be low in tumours with a RAS mutation. REGISTRATION: ClinicalTrials.govNCT00973609.

Snail odour-clouds: spreading and contribution to the transmission success of Trichobilharzia ocellata (Trematoda, Digenea) miracidia.

Chemical communication among freshwater organisms is an adaptation to improve their coexistence. Here,we focus on the chemical cues secreted by the freshwater gastropod Lymnaea stagnalis, which are known to stimulate behavioural responses of Trichobilharzia ocellata (Plathelminthes, Digenea, Trematoda) miracidia. Such responses are commonly claimed to influence transmission positively, but in response to chemical cues miracidia randomly change their swimming direction. This kind of response does not necessarily increase transmission, because miracidia may be trapped at the periphery of very large snail odour-clouds, which may prevent them from approaching the snail. On the other hand, the odour clouds may be too small to improve host-localisation. To shed light on these scenarios, the spreading of molecules released around L. stagnalis (active space) was visualised by recording host-finding responses of T. ocellata miracidia when they approached snails. Behavioural responses of miracidia indicated the spreading of compounds forming an attractive active space only around the host-snail L. stagnalis, but not around sympatric non-host-snail species. The active space increased approximately linearly with the time the snail rested at the same spot and within 5 min it reached a volume of more than 30 times that of the snail. We also demonstrated in a large-scale experiment, that the active space of L. stagnalis significantly increases the transmission success of T. ocellata miracidia. Additionally, the microhabitat selection of T. ocellata miracidia was studied, demonstrating that peripheral locations near the water surface were preferred, which are also preferred sites of L. stagnalis. Improved chemoperception and microhabitat selection may have been a consequence of coevolution with snails and benefited miracidia, which became efficient transmissive stages.

Detection of Schistosoma mansoni cercariae in plankton samples by PCR.

A PCR assay on the basis of a tandemly repeated DNA sequence was employed for the detection of Schistosoma mansoni in artificial plankton samples. It was highly specific, since as few as 1fg DNA from this species were sufficient to obtain a clear signal, while 10pg DNA of Schistosoma rodhaini were required and no PCR products were obtained with even 10ng DNA of planktonic organisms and any other trematode species tested. In areas with transmission of different Schistosoma species 10pg DNA should be used for amplification, which would allow detection of 20 S. mansoni cercariae in 0.05g plankton without interference caused by DNA of other Schistosoma species. In other areas 10ng DNA from plankton samples can be amplified, detecting less than one S. mansoni cercaria specifically in 0.05g plankton. This assay might help to identify S. mansoni in samples from field studies, where a multitude of different organisms hinder a correct species identification.

Detection of bird schistosomes in lakes by PCR and filter-hybridization.

Many lakes around the world are contaminated with bird schistosome cercariae, which penetrate into human skin, causing an itching dermatitis called "swimmers' itch." Bathers could be forewarned from exposure to the larvae and ecological examinations could be performed, when a sensitive method to detect the parasites in aquatic systems, where lots of organisms hinder microscopic examinations, would be available. For this purpose we cloned, sequenced, and analyzed a 396 bp tandem repeated DNA sequence from Trichobilharzia ocellata (ToSau3A), and employed it for developing molecular detection assays. It hybridized with less than 100 pg DNA from different Trichobilharzia species (T. ocellata, Trichobilharzia franki, and Trichobilharzia regenti), but not with 10 ng DNA from other related or sympatric trematodes. A PCR assay, amplifying this sequence with the same specificity, detected 100 fg T. ocellata DNA, 1 cercaria in 0.5 g plankton, and 2 cercariae in 0.5 g host snail tissues.