Quartz Crystal Microbalance With Dissipation Monitoring: A Versatile Tool to Monitor Phase Transitions in Biomimetic Membranes

Solid-supported lipid membranes are popular models that connect biological and artificial materials used in bio-technological applications. Controlling the lipid organization and the related functions of these model systems entails understanding and characterizing their phase behavior. Quartz crystal microbalance with dissipation monitoring (QCM-D) is an acoustic-based surface-sensitive technique which is widely used in bio-interfacial science of solid-supported lipid membranes. Its sensitivity to mass and energy dissipation changes at the solid-lipid layer-liquid interface allows the detection of phase transformations of solid-supported membrane geometries. In this perspective, we highlight this valuable feature and its related methodology, review current advances and briefly discuss future perspectives. Furthermore, a specific example is also provided on the ability of QCM-D to detect changes in lipid organization of cholesterol containing solid-supported lipid vesicle layers (SVLs) upon the addition of aspirin

Kinetics and crystallization path of a Fe-based metallic glass alloy

The thermal stability and the quantification of the different transformation processes involved in the overall crystallization of the Fe50Cr15Mo14C15B6 amorphous alloy were investigated by several characterization techniques. Formation of various metastable and stable phases during the devitrification process in the sequence a-Fe, ¿-Cr6Fe18Mo5, M23(C,B)6, M7C3, ¿-Fe3Mo3C and FeMo2B2 (with M = Fe, Cr, Mo), was observed by in-situ synchrotron high energy X-ray diffraction and in-situ transmission electron microscopy. By combining these techniques with differential scanning calorimetry data, the crystallization states and their temperature range of stability under continuous heating were related with the evolution of the crystallized fraction and the phase sequence as a function of temperature, revealing structural and chemical details of the different transformation mechanisms.Postprint (published version

Corrosion resistance of crystalline and amorphous CuZr alloys in NaCl aqueous environment and effect of corrosion inhibitors

CuZr alloys are the basis of a family of metallic glasses with large glass forming ability and remarkable mechanical properties. The corrosion response of prepared crystalline and amorphous CuxZr100-x alloys (x = 40, 50, 64 at%), as well as bare Cu and Zr, in a severe corrosive environment, was tested. The alloys were immersed in 3 wt% NaCl aqueous solution. With the aim to increase the resistance of copper as less corrosion alloy component, nine imidazole-based compounds with different functional groups were tested as potential corrosion inhibitors. Potentiodynamic polarization measurements, electrochemical impedance spectroscopy, and long-term immersion tests followed by X-ray photoelectron spectroscopy and microscopy analysis were carried out. Overall, all the tested amorphous alloys exhibit a much better corrosion resistance than their crystalline counterparts in the presence and absence of inhibitors. The main factor controlling the corrosion resistance of the alloys appears to be the Zr-rich (or at least equiatomic) amorphous structure, the effect of the inhibitors being secondary. Results therefore show a complex relationship between inhibitor performance, microstructure and composition of CuZr alloys.Peer ReviewedPostprint (published version

Glass-formation and corrosion properties of Fe-Cr-Mo-C-B glassy ribbons with low Cr content

The effect of low amounts of Cr on glass forming ability and corrosion behavior of Fe(65-x)CrxMo14C15B6 (x = 0, 2, 4, 6, 8,10 at.%) ribbons have been studied. It was found that the reduced glass transition temperature (T-rg) do not change significantly with Cr content. The glass forming ability (GFA) of this system is evaluated by the gamma(m), delta and omega parameters and the alloys containing 4 and 6 at.% were found to be the best glass formers in this system. The temperature interval of the supercooled liquid region (Delta T-x) changed with Cr and was enlarged from 35 K at x = 0 to 50 K at x = 4. Corrosion rates measured by immersion tests in H2SO4 decreased with an increase of chromium content in the alloys. The electrochemical measurements indicate that the alloys containing more than 4 at.% of Cr are spontaneously passivated with low current densities in 0.1 N H2SO4 whereas the alloys with Cr content <4 at.% showed transpassive Mo dissolution. In view of these results, the optimal amount of Cr addition in Fe-Mo-C-B amorphous steels is discussed. (C) 2014 Elsevier B.V. All rights reserved.Peer ReviewedPostprint (published version

A study protocol for a randomized trial testing the direct effects of cognitive behavioral therapy skill acquisition and role of learning capacity in depression

Background: To improve psychological treatments for major depressive disorder (MDD), a better understanding on how symptoms ameliorate during treatment is essential. In cognitive behavioral therapy (CBT), it is unclear whether procedures focused on the acquisition of CBT skills play a causal role in the improvement of CBT skills. In this randomized trial, we isolate a single CBT Skill Acquisition Procedure (CBTSAP) and test its direct effects on CBT skills and related therapy processes (i.e., change in (idiosyncratic) dysfunctional thinking and reward processing). We hypothesize that the CBTSAP causes improvements in CBT skills and related therapy processes compared to an active control condition. In addition, we hypothesize that individual differences in attentional bias and memory functioning (defined as learning capacity) moderate the effects of CBTSAP on outcomes and that using mental imagery as a cognitive support strategy to strengthen the effects of the CBTSAP will be most beneficial for patients with low learning capacity. Method: 150 patients with MDD will be randomized to one of three conditions: 1. an active control condition, 2. CBTSAP, 2. CBTSAP plus mental imagery, all consisting of three sessions. Primary outcomes will be change in CBT skills, changes in (idiosyncratic) dysfunctional thoughts and behaviors, reward processing. Depressive symptoms are a secondary outcome. Measures of learning capacity will be conducted at baseline and tested as a potential moderator. Discussion: Knowing whether and for whom the acquisition of CBT skills leads to change in therapy processes and a subsequent reduction of depressive symptoms will inform on how to personalize and optimize psychotherapy outcomes for depression. Trial registration: The trial is registered at the German Clinical Trial Register (DKTR; registration number: DRKS00024116)

Serious Adverse Drug Reactions in Children and Adolescents Treated On- and Off-Label with Antidepressants and Antipsychotics in Clinical Practice

Introduction: Despite the growing evidence base for psychotropic drug treatment in pediatric patients, knowledge about the benefit-risk ratio in clinical practice remains limited. The 'Therapeutic Drug Monitoring (TDM)-VIGIL' study aimed to evaluate serious adverse drug reactions (ADRs) in children and adolescents treated with antidepressants and/or antipsychotics in approved ('on-label'), and off-label use in clinical practice. Methods: Psychiatric pediatric patients aged 6-18 years treated with antidepressants and/or antipsychotics either on-label or off-label were prospectively followed between October 2014 and December 2018 within a multicenter trial. Follow-up included standardized assessments of response, serious ADRs and therapeutic drug monitoring. Results: 710 youth (age=14.6±2.2 years, female=66.6%) were observed for 5.5 months on average; 76.3% received antidepressants, 47.5% antipsychotics, and 25.2% both. Altogether, 55.2% of the treatment episodes with antidepressants and 80.7% with antipsychotics were off-label. Serious ADRs occurred in 8.3% (95%CI=6.4-10.6%) of patients, mainly being psychiatric adverse reactions (77.4%), predominantly suicidal ideation and behavior. The risk of serious ADRs was not significantly different between patients using psychotropics off-label and on-label (antidepressants: 8.1% vs. 11.3%, p=0.16; antipsychotics: 8.7% vs 7.5%, p=0.67). Serious ADRs occurred in 16.6% of patients who were suicidal at enrollment versus 5.6% of patients who were not suicidal (relative risk 3.0, 95%CI=1.9-4.9). Conclusion: Off-label use of antidepressants and antipsychotics in youth was not a risk factor for the occurrence of serious ADRs in a closely monitored clinical setting. Results from large naturalistic trials like ours can contribute to bridging the gap between knowledge from randomized controlled trials and real-world clinical settings

Therapeutic drug monitoring of sertraline in children and adolescents: A naturalistic study with insights into the clinical response and treatment of obsessive-compulsive disorder.

BACKGROUND Sertraline is a selective serotonin reuptake inhibitor with specific indications in child and adolescent psychiatry. Notwithstanding its frequent use and clinical benefits, the relationship between pharmacokinetics, pharmacodynamics, efficacy, and tolerability of sertraline across indications, particularly in non-adult patients, is not fully understood. METHOD This naturalistic therapeutic drug monitoring (TDM) study was conducted in a transdiagnostic sample of children and adolescents treated with sertraline (n = 78; mean age, 14.22 ± 2.39; range, 7-18 years) within the prospective multicenter "TDM-VIGIL" project. Associations between dose, serum concentration, and medication-specific therapeutic and side effects based on the Clinical Global Impression scale were examined. Tolerability was measured qualitatively with the 56-item Pediatric Adverse Event Rating Scale. RESULTS A strong linear positive dose-serum concentration relationship (with dose explaining 45% of the variance in concentration) and significant effects of weight and co-medication were found. Neither dose nor serum concentration were associated with side effects. An overall mild-to-moderate tolerability profile of sertraline was observed. In contrast with the transdiagnostic analysis that did not indicate an effect of concentration, when split into depression (MDD) and obsessive-compulsive disorder (OCD) diagnoses, the probability of clinical improvement significantly increased as both dose and concentration increased for OCD, but not for MDD. CONCLUSIONS This TDM-flexible-dose study revealed a significant diagnosis-specific effect between sertraline serum concentration and clinical efficacy for pediatric OCD. While TDM already guides clinical decision-making regarding compliance, dose calibration, and drug-drug interactions, combining TDM with other methods, such as pharmacogenetics, may facilitate a personalized medicine approach in psychiatry

Element-Resolved Corrosion Analysis of Stainless-Type Glass-Forming Steels

Ultrathin passive films effectively prevent the chemical attack of stainless steel grades in corrosive environments; their stability depends on the interplay between structure and chemistry of the constituents iron, chromium, and molybdenum (Fe-Cr-Mo). Carbon (C), and eventually boron (B), are also important constituents of steels, although in small quantities. In particular, nanoscale inhomogeneities along the surface can have an impact on material failure but are still poorly understood. Addressing a stainless-type glass-forming Fe50Cr15Mo14C15B6 alloy and using a combination of complementary high-resolution analytical techniques, we relate near-atomistic insights into increasingly inhomogeneous nanostructures with time- and element-resolved dissolution behavior. The progressive elemental partitioning on the nanoscale determines the degree of passivation. A detrimental transition from Cr-controlled passivity to Mo-controlled breakdown is dissected atom by atom, demonstrating the importance of nanoscale knowledge for understanding corrosionPostprint (published version

Differential Gene Expression from Microarray Analysis Distinguishes Woven and Lamellar Bone Formation in the Rat Ulna following Mechanical Loading

Formation of woven and lamellar bone in the adult skeleton can be induced through mechanical loading. Although much is known about the morphological appearance and structural properties of the newly formed bone, the molecular responses to loading are still not well understood. The objective of our study was to use a microarray to distinguish the molecular responses between woven and lamellar bone formation induced through mechanical loading. Rat forelimb loading was completed in a single bout to induce the formation of woven bone (WBF loading) or lamellar bone (LBF loading). A set of normal (non-loaded) rats were used as controls. Microarrays were performed at three timepoints after loading: 1 hr, 1 day and 3 days. Confirmation of microarray results was done for a select group of genes using quantitative real-time PCR (qRT-PCR). The micorarray identified numerous genes and pathways that were differentially regulated for woven, but not lamellar bone formation. Few changes in gene expression were evident comparing lamellar bone formation to normal controls. A total of 395 genes were differentially expressed between formation of woven and lamellar bone 1 hr after loading, while 5883 and 5974 genes were differentially expressed on days 1 and 3, respectively. Results suggest that not only are the levels of expression different for each type of bone formation, but that distinct pathways are activated only for woven bone formation. A strong early inflammatory response preceded an increase in angiogenic and osteogenic gene expression for woven bone formation. Furthermore, at later timepoints there was evidence of bone resorption after WBF loading. In summary, the vast coverage of the microarray offers a comprehensive characterization of the early differences in expression between woven and lamellar bone formation