Background
Careful selection of malignant pleural mesothelioma (MPM) patients for curative treatment is of highest importance, as the multimodal treatment regimen is challenging for patients and ...harbors a high risk of substantial toxicity. Radiomics—a quantitative method for image analysis—has shown its prognostic ability in different tumor entities and could therefore play an important role in optimizing patient selection for radical cancer treatment. So far, radiomics as a prognostic tool in MPM was not investigated.
Materials and methods
This study is based on 72 MPM patients treated with surgery in a curative intent at our institution between 2009 and 2017. Pre-treatment Fluorine-18 fluorodeoxyglucose (FDG) PET and CT scans were used for radiomics outcome modeling. After extraction of 1404 CT and 1410 FDG PET features from each image, a preselection by principal component analysis was performed to include only robust, non-redundant features for the cox regression to predict the progression-free survival (PFS) and the overall survival (OS). Results were validated on a separate cohort. Additionally, SUVmax and SUVmean, and volume were tested for their prognostic ability for PFS and OS.
Results
For the PFS a concordance index (c-index) of 0.67 (95% CI 0.52–0.82) and 0.66 (95% CI 0.57–0.78) for the training cohort (
n
= 36) and internal validation cohort (
n
= 36), respectively, were obtained for the PET radiomics model. The PFS advantage of the low-risk group translated also into an OS advantage. On CT images, no radiomics model could be trained. SUV max and SUV mean were also not prognostic in terms of PFS and OS.
Conclusion
We were able to build a successful FDG PET radiomics model for the prediction of PFS in MPM. Radiomics could serve as a tool to aid clinical decision support systems for treatment of MPM in future.
Abstract Cystic lesions of the pancreas are increasingly recognized. While some lesions show benign behaviour (serous cystic neoplasm), others have an unequivocal malignant potential (mucinous cystic ...neoplasm, branch- and main duct intraductal papillary mucinous neoplasm and solid pseudo-papillary neoplasm). European expert pancreatologists provide updated recommendations: diagnostic computerized tomography and/or magnetic resonance imaging are indicated in all patients with cystic lesion of the pancreas. Endoscopic ultrasound with cyst fluid analysis may be used but there is no evidence to suggest this as a routine diagnostic method. The role of pancreatoscopy remains to be established. Resection should be considered in all symptomatic lesions, in mucinous cystic neoplasm, main duct intraductal papillary mucinous neoplasm and solid pseudo-papillary neoplasm as well as in branch duct intraductal papillary mucinous neoplasm with mural nodules, dilated main pancreatic duct >6 mm and possibly if rapidly increasing in size. An oncological partial resection should be performed in main duct intraductal papillary mucinous neoplasm and in lesions with a suspicion of malignancy, otherwise organ preserving procedures may be considered. Frozen section of the transection margin in intraductal papillary mucinous neoplasm is suggested. Follow up after resection is recommended for intraductal papillary mucinous neoplasm, solid pseudo-papillary neoplasm and invasive cancer.
The aim of the present study was to examine the possibilities/advantages of using recently introduced in-line spectroscopic process analyzers (Raman, NIR and plasma emission spectroscopy), within ...well-designed experiments, for the optimization of a pharmaceutical formulation and its freeze-drying process. The formulation under investigation was a mannitol (crystalline bulking agent)–sucrose (lyo- and cryoprotector) excipient system. The effects of two formulation variables (mannitol/sucrose ratio and amount of NaCl) and three process variables (freezing rate, annealing temperature and secondary drying temperature) upon several critical process and product responses (onset and duration of ice crystallization, onset and duration of mannitol crystallization, duration of primary drying, residual moisture content and amount of mannitol hemi-hydrate in end product) were examined using a design of experiments (DOE) methodology. A 2-level fractional factorial design (25−1=16 experiments+3 center points=19 experiments) was employed. All experiments were monitored in-line using Raman, NIR and plasma emission spectroscopy, which supply continuous process and product information during freeze-drying. Off-line X-ray powder diffraction analysis and Karl-Fisher titration were performed to determine the morphology and residual moisture content of the end product, respectively.
In first instance, the results showed that – besides the previous described findings in De Beer et al., Anal. Chem. 81 (2009) 7639–7649 – Raman and NIR spectroscopy are able to monitor the product behavior throughout the complete annealing step during freeze-drying. The DOE approach allowed predicting the optimum combination of process and formulation parameters leading to the desired responses. Applying a mannitol/sucrose ratio of 4, without adding NaCl and processing the formulation without an annealing step, using a freezing rate of 0.9°C/min and a secondary drying temperature of 40°C resulted in efficient freeze-drying supplying end products with a residual moisture content below 2% and a mannitol hemi-hydrate content below 20%. Finally, using Monte Carlo simulations it became possible to determine how varying the factor settings around their optimum still leads to fulfilled response criteria, herewith having an idea about the probability to exceed the acceptable response limits. This multi-dimensional combination and interaction of input variables (factor ranges) leading to acceptable response criteria with an acceptable probability reflects the process design space.
Little is known about the factors that enable the mobilisation of human mesenchymal stem cells (MSC) from the bone marrow into the blood stream and their recruitment to and retention in the tumour. ...We found specific migration of MSC towards growth factors present in pancreatic tumours, such as PDGF, EGF, VEGF and specific inhibitors Glivec, Erbitux and Avastin interfered with migration. Within a few hours, MSC migrated into spheroids consisting of pancreatic cancer cells, fibroblasts and endothelial cells as measured by time-lapse microscopy. Supernatant from subconfluent MSC increased sprouting of HUVEC due to VEGF production by MSC itself as demonstrated by RT-PCR and ELISA. Only few MSCs were differentiated into endothelial cells in vitro, whereas in vivo differentiation was not observed. Lentiviral GFP-marked MSCs, injected in nude mice xenografted with orthotopic pancreatic tumours, preferentially migrated into the tumours as observed by FACS analysis of green fluorescent cells. By immunofluorescence and intravital microscopic studies, we found the interaction of MSC with the endothelium of blood vessels. Mesenchymal stem cells supported tumour angiogenesis in vivo, that is CD31(+) vessel density was increased after the transfer of MSC compared with siVEGF-MSC. Our data demonstrate the migration of MSC toward tumour vessels and suggest a supportive role in angiogenesis.
We report a simple approach for tailoring the morphology of poly(vinylidene fluoride) (PVDF) membranes fabricated using a nonsolvent induced phase separation (NIPS) method that sustains both the ...hydrophilic and hydrophobic properties. Various membrane structures,
skin layers and whole membrane structures as well, were obtained
an experimental method based on the obtained and computed ternary phase diagram. The nonsolvent interactions with polymer solution resulted in the different forms and properties of a surface layer of fabricated membranes that affected the overall transport of solvent and nonsolvent molecules inside and outside the bulk of the fabricated membranes. The resulting morphology and properties were confirmed using the 3D optical profiler, SEM, FT-IR and XRD methods. The effect of binary interaction parameters on the morphology of the fabricated membranes and on their separation performance was tested using water/oil mixture and gas separation. Both hydrophobic and hydrophilic properties of PVDF showed the excellent durable separation performance of the prepared membranes with 92% of oil separation and the maximum flux of 395 L h
m
along with 120 min of long-term stability. CO
separation from H
, N
, CH
and SF
gases was performed to further support the effect of tuned PVDF membranes with different micro/nanostructured morphologies. The gas performance demonstrated ultrahigh permeability and a several-fold greater than the Knudsen separation factor. The results demonstrate a facile and inexpensive approach can be successfully applied for the tailoring of the PVDF membranes to predict and design the resulting membrane structure.
Multi-axis differential optical absorption spectroscopy (MAX-DOAS) and direct sun NO2 vertical column network data are used to investigate the accuracy of tropospheric NO2 column measurements of the ...GOME-2 instrument on the MetOp-A satellite platform and the OMI instrument on Aura. The study is based on 23 MAX-DOAS and 16 direct sun instruments at stations distributed worldwide. A method to quantify and correct for horizontal dilution effects in heterogeneous NO2 field conditions is proposed. After systematic application of this correction to urban sites, satellite measurements are found to present smaller biases compared to ground-based reference data in almost all cases. We investigate the seasonal dependence of the validation results as well as the impact of using different approaches to select satellite ground pixels in coincidence with ground-based data. In optimal comparison conditions (satellite pixels containing the station) the median bias between satellite tropospheric NO2 column measurements and the ensemble of MAX-DOAS and direct sun measurements is found to be significant and equal to -34 % for GOME-2A and -24 % for OMI. These biases are further reduced to-24 % and -18 % respectively, after application of the dilution correction. Comparisons with the QA4ECV satellite product for both GOME-2A and OMI are also performed, showing less scatter but also a slightly larger median tropospheric NO2 column bias with respect to the ensemble of MAX-DOAS and direct sun measurements.
Over the last few decades, differential optical absorption spectroscopy (DOAS) has been used as a common technique to simultaneously measure abundances of a variety of atmospheric trace gases. ...Exploiting the unique differential absorption cross section of trace-gas molecules, mixing ratios can be derived by measuring the optical density along a defined light path and by applying the Beer-Lambert law. Active long-path (LP-DOAS) instruments can detect trace gases along a light path of a few hundred metres up to 20 km, with sensitivities for mixing ratios down to ppbv and pptv levels, depending on the trace-gas species. To achieve high measurement accuracy and low detection limits, it is crucial to reduce instrumental artefacts that lead to systematic structures in the residual spectra of the analysis. Spectral residual structures can be introduced by most components of a LP-DOAS measurement system, namely by the light source, in the transmission of the measurement signal between the system components or at the level of spectrometer and detector. This article focuses on recent improvements by the first application of a new type of light source and consequent changes to the optical setup to improve measurement accuracy.
We report on the fabrication of the defect-free mixed-matrix membrane (MMM) based on the polyethylenimine (PEI) matrix with uniformly dispersed metal-organic framework (MOF) filler UiO-66-NH2, ...covalently bonded by polyvinylpyrrolidone (PVP). The key feature of the molecular level-controlled filler deposition in prepared UiO-66-NH2-PVP-PEI membranes was bridging the MOF particles to the PEI polymer matrix via PVP polymer chains. Such an approach improved the polymer-filler interface interactions and boosted the MOF dispersion into the polymer matrix for higher MOF loadings up to 23 wt %. The overall membrane structure and properties were characterized using FTIR, XRD, TG, DSC, SEM and 3D optical profiler techniques. Obtained results revealed the uniform dispersion of UiO-66-NH2, the strong polymer-filler interface interactions and entanglement of PEI with UiO-66-NH2-PVP. Furthermore, the outstanding CO2/H2 separation performance was determined for the UiO-66-NH2-PVP-PEI membrane with 18 wt % of MOF loading; the average CO2 permeability of 394 Barrer and the separation factor of 12 for circa 100 h of the membrane testing overcome the 2008 Robeson reverse upper bound limit. Such improved CO2/H2 separation performance was achieved due to the combination of the diffusion-solution mechanism with the preferential adsorption of the CO2via the reversible bicarbonate reaction with amino groups of the UiO-66-NH2 and PEI which acts as fixed CO2 carrier sites in MMM structure.
Display omitted
•Fabricate new materials for CO2-selective membrane for hydrogen purification.•Strong polymer-filler interface interaction at the interface of UiO-66-NH2 and PEI.•Bridging approach by highly entangled polymer-filler for hydrogen purification.•Enhancement of mixture gas durability and thermal stability of the membrane.
Mangroves are one of the most carbon‐dense forests on the Earth and have been highlighted as key ecosystems for climate change mitigation and adaptation. Hundreds of studies have investigated how ...mangroves fix, transform, store, and export carbon. Here, we review and synthesize the previously known and emerging carbon pathways in mangroves, including gains (woody biomass accumulation, deadwood accumulation, soil carbon sequestration, root and litterfall production), transformations (food web transfer through herbivory, decomposition), and losses (respiration as CO2 and CH4, litterfall export, particulate and dissolved carbon export). We then review the technologies available to measure carbon fluxes in mangroves, their potential, and their limitations. We also synthesize and compare mangrove net ecosystem productivity (NEP) with terrestrial forests. Finally, we update global estimates of carbon fluxes with the most current values of fluxes and global mangrove area. We found that the contributions of recently investigated fluxes, such as soil respiration as CH4, are minor (<1 Tg C year−1), while the contributions of deadwood accumulation, herbivory, and lateral export are significant (>35 Tg C year−1). Dissolved inorganic carbon exports are an order of magnitude higher than the other processes investigated and were highly variable, highlighting the need for further studies. Gross primary productivity (GPP) and ecosystem respiration (ER) per area of mangroves were within the same order of magnitude as terrestrial forests. However, ER/GPP was lower in mangroves, explaining their higher carbon sequestration. We estimate the global mean mangrove NEP of 109.1 Tg C year−1 (7.4 Mg C ha−1 year−1) or through a budget balance, accounting for lateral losses, a global mean of 66.6 Tg C year−1 (4.5 Mg C ha−1 year−1). Overall, mangroves are highly productive, and despite losses due to respiration and tidal exchange, they are significant carbon sinks.
PDF
