Bounded Rationality in Principal‐Agent Relationships

We conducted six treatments of a standard moral hazard experiment with hidden action. All treatments had identical Nash equilibria. However, the behavior in all treatments and periods was inconsistent with established agency theory (Nash equilibrium). In the early periods of the experiment, behavior differed significantly between treatments. This difference largely vanished in the final periods. We used logit equilibrium (LE) as a device to grasp boundedly rational behavior and found the following: (1) LE predictions are much closer to subjects’ behavior in the laboratory; (2) LE probabilities of choosing between strategies and experimental behavior show remarkably similar patterns; and (3) profit‐maximizing contract offers according to the LE are close to those derived from regressions.experiment, logit equilibrium, moral hazard, hidden action

Individual contextual factors in the validation of the Bernese pain scale for neonates: protocol for a prospective observational study

Background: The Bernese Pain Scale for Neonates (BPSN) is a multidimensional pain assessment tool that is already widely used in clinical settings in the German speaking areas of Europe. Recent findings indicate that pain responses in preterm neonates are influenced by individual contextual factors, such as gestational age (GA), gender and the number of painful procedures experienced. Currently, the BPSN does not consider individual contextual factors. Therefore, the aim of this study is the validation of the BPSN using a large sample of neonates with different GAs. Furthermore, the influence of individual contextual factors on the variability in pain reactions across GA groups will be explored. The results will be used for a modification of the BPSN to account for individual contextual factors in future clinical pain assessment in neonates. Methods and design: This prospective multisite validation study with a repeated measures design will take place in three university hospital neonatal intensive care units (NICUs) in Switzerland (Bern, Basel and Zurich). To examine the impact of GA on pain responses and their variability, the infants will be stratified into six GA groups ranging from 24 0/7 to 42 0/7. Among preterm infants, 2–5 routine capillary heel sticks within the first 14 days of life, and among full-term infants, two heel sticks during the first days of life will be documented. For each heel stick, measurements will be video recorded for each of three phases: baseline, heel stick, and recovery. The infants’ pain responses will be rated according to the BPSN by five nurses who are blinded as to the number of each heel stick and as to the measurement phases. Individual contextual factors of interest will be extracted from patient charts. Discussion: Understanding and considering the influence of individual contextual factors on pain responses in a revised version of the BPSN will help the clinical staff to more appropriately assess pain in neonates, particularly preterm neonates hospitalized in NICUs. Pain assessment is a first step toward appropriate and efficient pain management, which itself is an important factor in later motor and cognitive development in this vulnerable patient population. Trial registration: The study is registered in the database of Clinical Trial gov. Study ID-number: NCT 02749461. Registration date: 12 April 2016. Keywords: Pain assessment, Premature infants, Contextual factors, Diagnosti

Synthesis, characterization, antibacterial and antitumoral activities of mononuclear zinc complexes containing tridentate amine based ligands with N3 or N2O donor groups

The synthesis and characterization of the four zinc(II) complexes [Zn(HL1)Cl-2] (1), [Zn(H2L2)Cl-2](2), [Zn(H2L3)Cl-2] (3) and[Zn(H2L4)Cl-2] (4), where HL1 = (bis-2-pyridylmethyl)amine, H2L2 = (2-hydroxybenzyl- 2-pyridylmethyl) amine, H2L3 = N-2[(pyridine-2-ylmethyl)amino)ethanol, H2L4 = 1-[(pyridine-2-ylmethyl)- amino]-propan-2-ol are reported; (3) and (4) are new while (2) was reported previously but its structure had not been determined. The complexes were characterized by elemental analysis, IR, UV-Vis and NMR spectroscopic, electrospray ionization mass spectrometry (ESI(+)-MS) and tandem mass spectrometry ESI(+)-MS/MS). X-ray diffraction studies were performed for complexes (1)-(3) revealing the presence of mononuclear structures in the solid state. The X-ray analyses of (1) and (3) demonstrate that HL1 and HL2 act as tridentate ligands, while the ligand H2L2 in (2) is bidentate. The cytotoxic properties of the ligands and of all the complexes were examined using human leukemia THP-1, U937 and Molt-4 cells. Complex (4) exhibited the highest cytotoxicity in this series with an IC50 value of 75 +/- 1 mu mol L (1) against U937 cells. Transmission electron microscopy (TEM) reveals ultrastructural changes typical of apoptotic cells. The induction of apoptosis was confirmed by the annexin V assay. The antimicrobial activity of complexes (1)-(4) was also investigated in vitro against four Gram-positive bacteria (ATCC10832, ATCC25923, COL) and the clinical Staphylococcus aureus isolate LSA88 (SEC/SEF/ TSST-1+). Complex (2) showed the most potent inhibitory activity, reaching almost 100% of inhibition against all strains tested. Morphological investigations using TEM indicate that the antibacterial activity of complex (2) may be associated with the inhibition of cell wall and therefore cell division. (C) 2014 Elsevier B. V. All rights reserved

A glutaminyl cyclase-catalyzed α-synuclein modification identified in human synucleinopathies

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is neuropathologically characterized by degeneration of dopaminergic neurons of the substantia nigra (SN) and formation of Lewy bodies and Lewy neurites composed of aggregated α-synuclein. Proteolysis of α-synuclein by matrix metalloproteinases was shown to facilitate its aggregation and to affect cell viability. One of the proteolysed fragments, Gln79-α-synuclein, possesses a glutamine residue at its N-terminus. We argue that glutaminyl cyclase (QC) may catalyze the pyroglutamate (pGlu)79-α-synuclein formation and, thereby, contribute to enhanced aggregation and compromised degradation of α-synuclein in human synucleinopathies. Here, the kinetic characteristics of Gln79-α-synuclein conversion into the pGlu-form by QC are shown using enzymatic assays and mass spectrometry. Thioflavin T assays and electron microscopy demonstrated a decreased potential of pGlu79-α-synuclein to form fibrils. However, size exclusion chromatography and cell viability assays revealed an increased propensity of pGlu79-α-synuclein to form oligomeric aggregates with high neurotoxicity. In brains of wild-type mice, QC and α-synuclein were co-expressed by dopaminergic SN neurons. Using a specific antibody against the pGlu-modified neo-epitope of α-synuclein, pGlu79-α-synuclein aggregates were detected in association with QC in brains of two transgenic mouse lines with human α-synuclein overexpression. In human brain samples of PD and dementia with Lewy body subjects, pGlu79-α-synuclein was shown to be present in SN neurons, in a number of Lewy bodies and in dystrophic neurites. Importantly, there was a spatial co-occurrence of pGlu79-α-synuclein with the enzyme QC in the human SN complex and a defined association of QC with neuropathological structures. We conclude that QC catalyzes the formation of oligomer-prone pGlu79-α-synuclein in human synucleinopathies, which may—in analogy to pGlu-Aβ peptides in Alzheimer’s disease—act as a seed for pathogenic protein aggregation

The Liver Tumor Segmentation Benchmark (LiTS)

In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LITS) organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2016 and International Conference On Medical Image Computing Computer Assisted Intervention (MICCAI) 2017. Twenty four valid state-of-the-art liver and liver tumor segmentation algorithms were applied to a set of 131 computed tomography (CT) volumes with different types of tumor contrast levels (hyper-/hypo-intense), abnormalities in tissues (metastasectomie) size and varying amount of lesions. The submitted algorithms have been tested on 70 undisclosed volumes. The dataset is created in collaboration with seven hospitals and research institutions and manually reviewed by independent three radiologists. We found that not a single algorithm performed best for liver and tumors. The best liver segmentation algorithm achieved a Dice score of 0.96(MICCAI) whereas for tumor segmentation the best algorithm evaluated at 0.67(ISBI) and 0.70(MICCAI). The LITS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.Comment: conferenc

Bounded rationality in principal-agent relationship

We conducted six treatments of a standard moral hazard experiment with hidden action. All treatments had identical Nash equilibria. However, the behavior in all treatments and periods was inconsistent with established agency theory (Nash equilibrium). In the early periods of the experiment, behavior differed significantly between treatments. This difference largely vanished in the final periods. We used logit equilibrium (LE) as a device to grasp boundedly rational behavior and found the following: (1) LE predictions are much closer to subjects' behavior in the laboratory; (2) LE probabilities of choosing between strategies and experimental behavior show remarkably similar patterns; and (3) profit‐maximizing contract offers according to the LE are close to those derived from regressions

Vitrimer composites: current status and future challenges

International audienceThermosets dominate the composite industry owing to their outstanding stiffness to weight ratio and fatigue resistance. Nevertheless, the possibilities of recycling these materials are limited due to the irreversible chemical bonds created during the curing process which cause the materials to be set in their final form. The available recycling strategies generally degrade the polymer matrix either by burning off (pyrolysis) or chemically dissolving (solvolysis) the resins in order to recover the fibres. But methodologies to reprocess or fully recycle (i.e. resin + fibres) these composite materials are rare. Thus, the development of more sustainable approaches is now increasing importantly and is seen as a decisive challenge for the further development of composite materials. Vitrimer materials, which combine the mechanical resilience of thermosets with reprocessability of “glass” at high temperatures, appear as a very promising alternative towards recyclable thermoset composites. This review gathers the recent progress in the domain of vitrimer composites and points out the next future challenges to be tackled. A brief section discussing the first industrial initiatives is also presented

Exploring the Limits of High- T g Epoxy Vitrimers Produced through Resin-Transfer Molding

International audienceOver the past few years, scientists have developed new ways to overcome the recycling issues of conventional thermosets with the introduction of associative covalent adaptable networks (i.e., vitrimers) in polymer materials. Even though various end-use vitrimers have already been reported, just a few of them have targeted high performance industrial applications. Herein, we develop a promising high-performance epoxy vitrimer based on a commercially available resin widely used in aeronautics with the highest glass transition temperature (Tg) of 233 °C ever reported for a vitrimer. A complete study of its physicochemical properties and cure kinetics was conducted, enabling the construction of the first time−temperature−transformation (TTT) diagram reported in the literature. This diagram allows a full determination of the processing and curing parameters leading to the manufacturing of vitrimer samples by the resin-transfer molding (RTM) process. The reshapability and limits therefrom of this high-Tg vitrimer were evaluated by three successful thermoforming cycles without degradation

Acute Effects of Focused Ultrasound-Induced Blood-Brain Barrier Opening on Anti-Pyroglu3 Abeta Antibody Delivery and Immune Responses

Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid plaques and hyperphosphorylated tau in the brain. Currently, therapeutic agents targeting amyloid appear promising for AD, however, delivery to the CNS is limited due to the blood-brain-barrier (BBB). Focused ultrasound (FUS) is a method to induce a temporary opening of the BBB to enhance the delivery of therapeutic agents to the CNS. In this study, we evaluated the acute effects of FUS and whether the use of FUS-induced BBB opening enhances the delivery of 07/2a mAb, an anti-pyroglutamate-3 Aβ antibody, in aged 24 mo-old APP/PS1dE9 transgenic mice. FUS was performed either unilaterally or bilaterally with mAb infusion and the short-term effect was analyzed 4 h and 72 h post-treatment. Quantitative analysis by ELISA showed a 5–6-fold increase in 07/2a mAb levels in the brain at both time points and an increased brain-to-blood ratio of the antibody. Immunohistochemistry demonstrated an increase in IgG2a mAb detection particularly in the cortex, enhanced immunoreactivity of resident Iba1+ and phagocytic CD68+ microglial cells, and a transient increase in the infiltration of Ly6G+ immune cells. Cerebral microbleeds were not altered in the unilaterally or bilaterally sonicated hemispheres. Overall, this study shows the potential of FUS therapy for the enhanced delivery of CNS therapeutics