I introduce unobservable costly effort into the canonical signalling model of security design. The choice of effort determines the quality of the security and creates an additional optimisation ...problem the firm must solve. My main result is that both optimal effort and optimal profits are decreasing in the firm’s preference for liquidity. I also show that optimal effort is greater under symmetric information. My approach provides a theoretical explanation for empirical results that cannot be obtained within the standard signalling framework. In addition, I extend existing methods to solve signalling models with endogenous private information.
•Costly effort is introduced into the seminal model of security design.•Optimal effort and profits are decreasing in the firm’s preference for liquidity.•Optimal effort is therefore greater under symmetric information.•The analysis provides a theoretical explanation for empirical results.
Multiple comparisons tests (MCTs) include the statistical tests used to compare groups (treatments) often following a significant effect reported in one of many types of linear models. Due to a ...variety of data and statistical considerations, several dozen MCTs have been developed over the decades, with tests ranging from very similar to each other to very different from each other. Many scientific disciplines use MCTs, including >40,000 reports of their use in ecological journals in the last 60 years. Despite the ubiquity and utility of MCTs, several issues remain in terms of their correct use and reporting. In this study, we evaluated 17 different MCTs. We first reviewed the published literature for recommendations on their correct use. Second, we created a simulation that evaluated the performance of nine common MCTs. The tests examined in the simulation were those that often overlapped in usage, meaning the selection of the test based on fit to the data is not unique and that the simulations could inform the selection of one or more tests when a researcher has choices. Based on the literature review and recommendations: planned comparisons are overwhelmingly recommended over unplanned comparisons, for planned non-parametric comparisons the Mann-Whitney-Wilcoxon
test is recommended, Scheffé's
test is recommended for any linear combination of (unplanned) means, Tukey's HSD and the Bonferroni or the Dunn-Sidak tests are recommended for pairwise comparisons of groups, and that many other tests exist for particular types of data. All code and data used to generate this paper are available at: https://github.com/stevemidway/MultipleComparisons.
The dead donor rule is fundamental to transplant ethics. The rule states that organ procurement must not commence until the donor is both dead and formally pronounced so, and by the same token, that ...procurement of organs must not cause the death of the donor. In a separate area of medical practice, there has been intense controversy around the participation of physicians in the execution of capital prisoners. These two apparently disparate topics converge in a unique case: the intimate involvement of transplant surgeons in China in the execution of prisoners via the procurement of organs. We use computational text analysis to conduct a forensic review of 2838 papers drawn from a dataset of 124 770 Chinese‐language transplant publications. Our algorithm searched for evidence of problematic declarations of brain death during organ procurement. We find evidence in 71 of these reports, spread nationwide, that brain death could not have properly been declared. In these cases, the removal of the heart during organ procurement must have been the proximate cause of the donor's death. Because these organ donors could only have been prisoners, our findings strongly suggest that physicians in the People's Republic of China have participated in executions by organ removal.
A computational text analysis of over 2,000 Chinese‐language medical publications finds that transplant surgeons in the People's Republic of China have participated in the execution of prisoners by procuring their organs before brain death was determined.
This article presents a new modular robotic platform for enabling reconfigurable, actively controlled, high-degree-of-freedom (high-DoF) systems with compact form factor. The robotic modules exploit ...the advantages of origami-inspired construction methods and materials, and soft pneumatic actuators (SPAs) to achieve an actuator embedded, parallel kinematic mechanism with three independently controlled “waterbomb” base legs. The multi-material, layer-fabricated body of the modules features selectively compliant flexure hinge elements between rigid panels that define the module as a kinematic 6R spherical joint. The precision layer-fabrication technique is also used to form embedded distribution channels within the module base to connect actuators to onboard control hardware. A decentralized control architecture is applied by integrating each module with small-scale solenoid valves, communication electronics, and sensors. This design approach enables a single pneumatic supply line to be shared between modules, while still allowing independent control of each leg joint, driven by soft, inflatable pouch actuators. A passive pneumatic relay is also designed and incorporated in each module to leverage the coupled, inverted inflation, and exhaust states between antagonistic actuator pairs allowing both to be controlled by a single solenoid valve. A prototype module is presented as the first demonstration of integrated modular origami and SPA design, or pneumagami, which allows predefined kinematic structural mechanisms to locally prescribe specific motions by active effect, not just through passive compliance, to dictate task space and motion. The design strategy facilitates the composition of lightweight, high-strength robotic structures with many DoFs that will benefit various fields such as wearable robotics.
The mechanical behavior of high quality two-dimensional (2D) crystals offers exciting opportunities for new material design, such as the combination of extremely high in-plane stiffness and bending ...flexibility, compared to existing three-dimensional (3D) material forms. By combining different 2D crystals vertically or by in-plane stitching, unusual properties can arise due to nonlinear mechanical interactions between them. Van der Waals forces between vertically stacked crystals give rise to a wide range of useful phenomena such as layer-number dependent friction, superlubricity, creasing, and spatial modulation of elastic properties through Moiré structures. In the present article, we review and explain the mechanical behavior of 2D materials and heterostructures (graphene, hexagonal boron nitride, transition metal dichalcogenides). Linear elastic properties of these 2D crystalline monolayers are well-studied using membrane nanoindentation towards their application in nano-electro-mechanical systems (NEMS) devices. On the other hand, a more thorough understanding of friction, fracture and stress transfer mechanisms between 2D layers and with the substrate or matrix is still lacking. More in-depth understanding of geometry-dependent behavior could enable the application of these materials in multi-functional composites. We discuss emerging opportunities achievable by assembling 2D heterostructures to tailor their mechanical behavior, and perhaps even break the traditional bounds limiting the properties of the bulk homostructures. Furthermore, to accelerate the design and discovery of the infinite combinations of new 2D heterostructures, we construct a crowd-sourced searchable online database to record and exploit the studies reporting on the complex arrangements of these crystals.
Perfusion decellularization of cadaveric hearts removes cells and generates a cell-free extracellular matrix scaffold containing acellular vascular conduits, which are theoretically sufficient to ...perfuse and support tissue-engineered heart constructs. However, after transplantation, these acellular vascular conduits clot, even with anti-coagulation. Here, our objective was to create a less thrombogenic scaffold and improve recellularized-left ventricular contractility by re-lining vascular conduits of a decellularized rat heart with rat aortic endothelial cells (RAECs).
We used three strategies to recellularize perfusion-decellularized rat heart vasculature with RAECs: retrograde aortic infusion, brachiocephalic artery (BA) infusion, or a combination of inferior vena cava (IVC) plus BA infusion. The re-endothelialized scaffolds were maintained under vascular flow in vitro for 7 days, and then cell morphology, location, and viability were examined. Thrombogenicity of the scaffold was assessed in vitro and in vivo. Both BA and IVC+BA cell delivery resulted in a whole heart distribution of RAECs that proliferated, retained an endothelial phenotype, and expressed endothelial nitric oxide synthase and von Willebrand factor. Infusing RAECs via the combination IVC+BA method increased scaffold cellularity and the number of vessels that were lined with endothelial cells; re-endothelialization by using BA or IVC+BA cell delivery significantly reduced in vitro thrombogenicity. In vivo, both acellular and re-endothelialized scaffolds recruited non-immune host cells into the organ parenchyma and vasculature. Finally, re-endothelialization before recellularization of the left ventricular wall with neonatal cardiac cells enhanced construct contractility.
This is the first study to re-endothelialize whole decellularized hearts throughout both arterial and venous beds and cavities by using arterial and venous delivery. The combination (IVC+BA) delivery strategy results in enhanced scaffold vessel re-endothelialization compared to single-route strategies. Re-endothelialization reduced scaffold thrombogencity and improved contractility of left ventricular-recellularized constructs. Thus, vessel and cavity re-endothelialization creates superior vascularized scaffolds for use in whole-organ recellularization applications.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patients treated with chimeric antigen receptor (CAR) T cell therapy often develop severe neurological toxicities associated with focal neurological deficits that are incompletely understood. Rubin ...et al. catalogue the neurological symptoms in 100 consecutive patients receiving CAR T cell therapy, characterizing the common clinical features and diagnostic findings.
Abstract
Chimeric antigen receptor T cell therapy has become an important tool in the treatment of relapsed and refractory malignancy; however, it is associated with significant neurological toxicity. We characterized the neurological toxicity associated with chimeric antigen receptor T-cell therapy in a consecutive series of 100 patients up to 2 months post transfusion, 28 of whom were obtained from chart review and the others by prospective observation. The underlying neoplasms were lymphoma (74%), myeloma (14%), leukaemia (10%), and sarcoma (2%). The median age of the cohort was 64.5 years old and 39% of patients were female. The most commonly occurring neurological symptoms were encephalopathy (57%), headache (42%), tremor (38%), aphasia (35%) and focal weakness (11%). Focal neurological deficits are frequently observed after chimeric antigen receptor T-cell therapy and are associated with regional EEG abnormalities, FDG-PET hypometabolism, and elevated velocities on transcranial Doppler ultrasound. In contrast, structural imaging was typically normal. As this form of treatment is more widely adopted, recognition of the frequently encountered symptoms will be of increasing importance for the neurologists and oncologists caring for this growing patient population.
Genetic influences on gene expression in the human fetal brain plausibly impact upon a variety of postnatal brain-related traits, including susceptibility to neuropsychiatric disorders. However, to ...date, there have been no studies that have mapped genome-wide expression quantitative trait loci (eQTL) specifically in the human prenatal brain.
We performed deep RNA sequencing and genome-wide genotyping on a unique collection of 120 human brains from the second trimester of gestation to provide the first eQTL dataset derived exclusively from the human fetal brain. We identify high confidence cis-acting eQTL at the individual transcript as well as whole gene level, including many mapping to a common inversion polymorphism on chromosome 17q21. Fetal brain eQTL are enriched among risk variants for postnatal conditions including attention deficit hyperactivity disorder, schizophrenia, and bipolar disorder. We further identify changes in gene expression within the prenatal brain that potentially mediate risk for neuropsychiatric traits, including increased expression of C4A in association with genetic risk for schizophrenia, increased expression of LRRC57 in association with genetic risk for bipolar disorder, and altered expression of multiple genes within the chromosome 17q21 inversion in association with variants influencing the personality trait of neuroticism.
We have mapped eQTL operating in the human fetal brain, providing evidence that these confer risk to certain neuropsychiatric disorders, and identifying gene expression changes that potentially mediate susceptibility to these conditions.
The perturbation of metabolic pathways in high-grade bladder cancer has not been investigated. We aimed to identify a metabolic signature in high-grade bladder cancer by integrating unbiased ...metabolomics, lipidomics, and transcriptomics to predict patient survival and to discover novel therapeutic targets.
We performed high-resolution liquid chromatography mass spectrometry (LC-MS) and bioinformatic analysis to determine the global metabolome and lipidome in high-grade bladder cancer. We further investigated the effects of impaired metabolic pathways using
models.
We identified 519 differential metabolites and 19 lipids that were differentially expressed between low-grade and high-grade bladder cancer using the NIST MS metabolomics compendium and lipidblast MS/MS libraries, respectively. Pathway analysis revealed a unique set of biochemical pathways that are highly deregulated in high-grade bladder cancer. Integromics analysis identified a molecular gene signature associated with poor patient survival in bladder cancer. Low expression of CPT1B in high-grade tumors was associated with low FAO and low acyl carnitine levels in high-grade bladder cancer, which were confirmed using tissue microarrays. Ectopic expression of the CPT1B in high-grade bladder cancer cells led to reduced EMT in
, and reduced cell proliferation, EMT, and metastasis
.
Our study demonstrates a novel approach for the integration of metabolomics, lipidomics, and transcriptomics data, and identifies a common gene signature associated with poor survival in patients with bladder cancer. Our data also suggest that impairment of FAO due to downregulation of CPT1B plays an important role in the progression toward high-grade bladder cancer and provide potential targets for therapeutic intervention.
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