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The objective of this work is to develop and evaluate experimental approaches with different analytical techniques to measure the permeability, diffusivity, and solubility of water in model coatings. These properties are of primary relevance in studies of coatings for corrosion protection. For water permeation measurements, setups were designed and prepared to facilitate measurements by microcalorimetry, gravimetry, and thermogravimetric analysis. For sorption measurements, films were prepared in various thicknesses to allow a proper analysis with Fourier-transform infrared spectroscopy in transmission mode and gravimetry. Both methods are successful in following water uptake kinetic curves, being complementary in film thickness ranges that can be analyzed. The validity of the permeabilities calculated from permeation measurements is compared to results from group contribution methods and reported values in the literature. Diffusivities were determined using data from the transient region in sorption and permeation measurements, as well as from the steady-state permeation rate and equilibrium solubility in permeation and sorption measurements, respectively.

ABSTRACTIntroduction: Given the well-documented difficulty to treat perianal fistulizing Crohn’s disease (pCD), with 40% of patients experiencing recurrence even after reiterative surgery and advanced medical therapy, research in this field has focused on the role of mesenchymal stem cells (MSC).Areas covered: The aim of this article is to furnish an overview of the pathogenetic mechanisms, clinical applications and evidences for the use of MSC for pCD with particular focus on adipose-derived allogenic MSC including darvadstrocel.Expert Opinion: The effect of MSC on fistula healing is probably mediated by their anti-inflammatory properties more than by their ability to engraft and trans-differentiate in the healthy tissue. A holistic treatment of pCD, addressing different pathophysiological factors, may represent the key for an improvement in the healing rate. In this setting, MSC might play a role as ‘augmentation’ therapy in combination with more conventional treatments. Whether MSC have benefit in non-complex fistula in biological naïve patients, in complex fistula with many tracts and/or in rectovaginal fistulas, are unexplored fields that need further investigation. A central registry of pCD patients undergoing treatment with MSC should be created in order to elucidate the efficacy, safety and costs of stem cells treatment on long term follow up.

ObjectiveCiclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab.DesignBetween 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test.ResultsAfter a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment.ConclusionsIn this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other.Trial registration numberEudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.

The crystallization of semi-crystalline polymers is often analyzed by rheometry and calorimetry. By rheometry the viscosity evolution during crystallization can be followed, whereas from a calorimetric measurement, the evolution of the degree of crystallinity can be calculated. The time evolution of these material properties is valuable input for polymer processing simulation software and in order to combine the data in a reliable manner, hardening curves are used as a characterization tool. Such a hardening curve correlates the relative increase of the viscosity resulting from crystallization, to the advancing degree of crystallinity. In this study, these are extracted from simultaneous measurements on one sample using a RheoDSC device. The RheoDSC technique allows for the direct combination of the rheological and calorimetric signal without the need of combining separate stand-alone measurement results. In this study, isothermal crystallization experiments are used to discuss the benefits of this approach. This will lead to the recommendation that measuring the hardening effect in steady shear measurements at very low shear rates in a direct combined RheoDSC setup is the most reliable method to compile unambiguously a material specific hardening curve for semi-crystalline polymers.

The natural history of Crohn's disease is characterized by progression to complicated and disabling disease, often necessitating surgical interventions. There is either circumstantial or direct evidence to support the disease-modifying potential of several therapeutic agents. Healing of endoscopic lesions is an emerging surrogate marker of disease modification, as mucosal lesions are considered to reflect ongoing inflammation and tissue damage that lead to the formation of fistulas and fibrotic strictures, which are the main indications for surgery. In contrast to systemic steroids, both azathioprine and anti-tumor necrosis factor (TNF) agents have demonstrated the potential of mucosal healing. Prevention of hospitalization and surgery in the short and medium term has been demonstrated for the anti-TNF agents infliximab and adalimumab. The evidence supporting a role for medical therapy in the prevention of fibrotic wall thickening and in the obliteration of fistula tracks is limited and should be the focus of further prospective studies. These studies should validate predictors of complicated disease and randomized studies should be performed in high-risk groups to investigate whether early introduction of immunosuppressive agents or biologic therapies slows down disease progression and alters the natural history of the disease.

The conversion of hkalkylsulfinyl OC1C10-PPV precursor polymers to the conjugated OC1C10-PPV polymer and the subsequent reactions of the elimination products in the solid state are studied in situ with FT-IR, UV−vis spectroscopy, and modulated temperature DSC (MTDSC). FT-IR and UV−vis spectroscopy allow monitoring the formation of double bonds in the conjugated system. The experimental activation energy of this conversion reaction is in good agreement with the value from theoretical modeling (101 kJ/mol). Quasi-isothermal MTDSC heat capacity measurements permit the characterization of the subsequent reaction steps of the elimination products (dimerization of sulfenic acid and disproportionation of thiosulfinate). The formation of water in the dimerization step and elimination products results in a positive reaction heat capacity (ΔrCp). This increase in heat capacity is slower than the formation of double bonds, which is attributed to the fact that the dimerization and disproportionation reactions behave as consecutive reactions relative to the elimination reaction of sulfenic acid. The amount of water released in isothermal conditions can be calculated from subsequent nonisothermal MTDSC experiments and can be used as an independent measure for the extent of the dimerization reaction. Isothermal and nonisothermal MTDSC experiments in solution have shown that phase separation between the polymer and the solvent occurs. In the nonisothermal experiment a small baseline shift is visible in the heat capacity signal at high temperature, which is an indication of phase separation. In the isothermal experiments, the increase in heat capacity is larger for the elimination in solution compared to the elimination in solid state, which is also an indication not only that the increase in heat capacity is due to the elimination process itself but also that phase separation interferes beyond a certain conversion. Phase separation in isothermal conditions is also demonstrated with UV−vis spectroscopy.

Endoscopy is arguably the golden standard for the initial diagnosis of Crohn's disease (CD), but the role of endoscopic mucosal healing in the assessment of treatment response or in predicting the course of the disease is more controversial. Endoscopic indices of severity have been developed but have failed to correlate with response to standard treatments such as corticosteroids and aminosalicylates. Immunosuppressives induce mucosal healing with an interval of months. The anti-TNF monoclonal antibody infliximab, leads to rapid and complete disappearance of mucosal ulcers. Clinical improvement with infliximab also correlates with improvement in the endoscopic severity index. Systematic 8 weekly maintenance treatment with infliximab induces mucosal healing as long as the therapy is continued. However, clinical trial and practice experience indicate that the healing of the mucosa does not persist when infliximab is interrupted. The dramatic effect of infliximab on endoscopic mucosal healing has reset the standards for future drug development, but several questions remain unanswered. It is still unclear whether endoscopic healing predicts a long-term favorable outcome. Also data demonstrating that endoscopic healing prevents complications are limited and should be confirmed. However, at this moment the body of evidence supporting the use of mucosal healing as an objective biological parameter of short-term efficacy in CD is sufficient to consider endoscopy as an essential component of clinical trial outcomes.

BackgroundHealing of mucosal lesions appears to offer significant benefit and is an important end point in clinical trials of treatment for Crohn's disease. The only validated endoscopic activity score at present is the Crohn's Disease Endoscopic Index of Severity, which is complicated and time consuming and, hence, is unsuitable for routine use. The aim of this study was to develop and to prospectively validate a simpler endoscopic score of disease activity, the Simple Endoscopic Score for Crohn's Disease.MethodsSelected endoscopic parameters (ulcer size, ulcerated and affected surfaces, stenosis) were scored from 0 to 3. Reproducibility for scoring of these parameters was evaluated through 71 examinations in which the endoscopist was paired with an observer. The simplest score (Simple Endoscopic Score for Crohn's Disease) that was highly correlated with both the Crohn's Disease Endoscopic Index of Severity and Crohn's Disease Activity Index was derived for 70 patients and then was prospectively validated in 121 different patients with Crohn's disease.ResultsThe interobserver agreement for all selected endoscopic variables was excellent (kappa coefficient 0.791-1.000). Based on multiple linear regression, the Simple Endoscopic Score for Crohn's Disease resulted in the sum of the scores for ulcer size, ulcerated surface, affected surface, and luminal narrowing. In the validation phase of the study, a strong correlation was demonstrated for the Simple Endoscopic Score for Crohn's Disease with Crohn's Disease Endoscopic Index of Severity (r=0.920). In addition, the Simple Endoscopic Score for Crohn's Disease was correlated to clinical parameters and serum C-reactive protein level.ConclusionsSimple Endoscopic Score for Crohn's Disease is a simple, reproducible, and easy-to-use endoscopic scoring system for Crohn's disease.

Abstract:: The cloning of quantum variables with continuous spectra is investigated. We define a Gaussian 1-to-2 cloning machine that copies equally well two conjugate variables such as position and momentum or the two quadrature components of a light mode. The resulting cloning fidelity for coherent states, namely F = 2/3, is shown to be optimal. An asymmetric version of this Gaussian cloner is then used to assess the security of a continuous-variable quantum key distribution scheme that allows two remote parties to share a Gaussian key. The information versus disturbance tradeoff underlying this continuous quantum cryptographic scheme is then analyzed for the optimal individual attack. Methods to convert the resulting Gaussian keys into secret key bits are also studied. Finally, the extension of the Gaussian cloner to optimal N-to-M continuous cloners is discussed, and it is shown how to implement these cloners for light modes using a phase-insensitive optical amplifier and beam splitters. In addition, a phase-conjugate input cloner is defined, yielding M clones and M' anticlones from N replicas of a coherent state and N' replicas of its phase-conjugate (with M' - M = N' - N). This novel kind of cloners is shown to outperform the standard N-to-M cloners in some cases.

The free radical chain-growth cross-linking copolymerisation of an unsaturated polyester resin with styrene is investigated in isothermal conditions using different techniques. By modulated temperature differential scanning calorimetry (MTDSC) the rate of polymerisation is observed simultaneously with the (partial) vitrification of the reacting material. An important autoacceleration closely before vitrification corresponds to an accelerating styrene consumption. The autoacceleration occurs long after the gelation of the material, which implies that termination reactions involving small radicals are still important at an advanced conversion. The deceleration of these termination reactions causes the autoacceleration, which is stopped when the propagation reaction slows down due to vitrification. MTDSC proves to be very suitable for studying the interrelations between vitrification and the polymerisation kinetics.

The free radical cross-linking copolymerization of an unsaturated polyester resin with styrene is studied in isothermal conditions using temperature modulated differential scanning calorimetry (TMDSC) and dynamic rheometry. The dynamic rheometry measurements show that gelation occurs at a conversion below 5%, while TMDSC measurements show that an important autoacceleration starts near 60% conversion, giving rise to a maximum cure rate closely before the (partial) vitrification of the system near 80%. This indicates that the autoacceleration is not due to the sharp increase in bulk viscosity at gelation, but rather to a change in molecular mobilities at higher conversion.

Abstract: The influence of temperature modulation and signal treatment (deconvolution procedure) of modulated temperature differential scanning calorimetry is discussed with respect to the investigation of cure kinetics of thermosetting systems. The use of a ‘dynamic’ heat capacity calibration is not important for this purpose due to normalization of the heat capacity signal in all cure experiments. The heat flow phase during isothermal and non-isothermal cure is always small, giving rise to negligible corrections on the heat capacity and reversing heat flow signals in-phase with the modulated heating rate. The evolution of the heat flow phase contains information on relaxation phenomena in the course of the chemical reactions.

The benefits of temperature-modulated differential scanning calorimetry to characterize reacting polymers are illustrated for different experimental systems. The effects of combined isothermal and non-isothermal cure paths on (de)vitrification, mobility-restricted reactions, and relaxation during vitrification are discussed for anhydride- and amine-cured epoxies. The simultaneous measurement of heat capacity, heat flow, and heat flow phase provides an excellent tool for mechanistic interpretations. The influence of the metakaolinite particle size on the production of inorganic silicate-metakaolinite polymer glasses is treated as an example. These principles are further illustrated for primary and secondary amine-epoxy step growth reactions, and for styrene-cured unsaturated polyester chain growth reactions with ‘gel effect’. Finally, the effects of isothermal cure and temperature on reaction-induced phase separation in a polyethersulfone modified epoxy-amine system are highlighted.

BACKGROUND & AIMS: Exposure of rat longitudinal muscle myenteric plexus to the proinflammatory cytokine interleukin (IL) 1 beta mimics the effects of nematode infection on enteric nerve function through a hitherto unidentified protein intermediate. It is postulated that leukemia inhibitory factor (LIF), the downstream intermediate of several IL-1-induced neuroimmune interactions, mediates IL-1 beta- induced suppression of acetylcholine release from rat jejunum. METHODS: Preparations were preloaded with [3H]choline, and [3H]-acetylcholine release was induced by either electrical field stimulation or by 50 mmol/L KCl. Cytokines and anti-LIF antibodies were added to the preincubation media or to the superfusate before stimulation. RESULTS: Human recombinant LIF had no immediate effects, but preincubation with the cytokine induced a concentration-dependent (2-100 ng/mL) and reversible suppression of acetylcholine release from rat longitudinal muscle myenteric plexus. The effects of human recombinant LIF on acetylcholine release were reversed by anti-human recombinant LIF- neutralizing antibody. Human recombinant IL-1 beta (10 ng/mL) induced a similar suppression of acetylcholine release, and the addition of anti- rat LIF antibody abolished the effects of exogenous IL-1 on acetylcholine release. CONCLUSIONS: IL-1 beta suppresses neurotransmitter release from rat myenteric plexus via the induction of LIF as a downstream intermediate. (Gastroenterology 1996 Sep;111(3):674-81)