Convergence of finite difference method for the generalized solutions of Sobolev equations

In this paper, finite difference method is applied to approximate the generalized solutions of Sobolev equations. Using the Steklov mollifier and BrambleHilbert Lemma, a priori error estimates in discrete L2 as well as in discrete H1 norms are derived first for the semidiscrete methods. For the fully discrete schemes, both backward Euler and CrankNicolson methods are discussed and related error analyses are also presented

Acoustic horizons for axially and spherically symmetric fluid flow

We investigate the formation of acoustic horizons for an inviscid fluid moving in a pipe in the case of stationary and axi-symmetric flow. We show that, differently from what is generally believed, the acoustic horizon forms in correspondence of either a local minimum or maximum of the flux tube cross-section. Similarly, the external potential is required to have either a maximum or a minimum at the horizon, so that the external force has to vanish there. Choosing a power-law equation of state for the fluid, $P\propto \rho^{n}$, we solve the equations of the fluid dynamics and show that the two possibilities are realized respectively for $n>-1$ and $n<-1$. These results are extended also to the case of spherically symmetric flow.Comment: 6 pages, 3 figure

Morphological and Mechanical Biomimetic Bone Structures

© 2016 American Chemical Society. Cortical bone is an example of a mineralized tissue containing a compositional distribution of hard and soft phases in 3-dimensional space for mechanical function. X-ray computed tomography (XCT) is able to describe this compositional and morphological complexity but methods to provide a physical output with comparable mechanical function is lacking. A workflow is presented here to establish a method of using high contrast XCT to establish a virtual model of cortical bone that is manufactured using a multiple material capable 3D printer. Resultant 3D printed structures were produced based on more and less remodelled bone designs exhibiting a range of secondary osteon density. Variation in resultant mechanical properties of the 3D printed composite structures for each bone design was achieved using a combination of material components and reasonable prediction of elastic modulus provided using a Hashin-Shtrikman approach. The ability to 3D print composite structures using high contrast XCT to distinguish between compositional phases in a biological structure promises improved anatomical models as well as next-generation mechano-mimetic implants

Magneto Seebeck effect in REFeAsO (RE=rare earth) compounds: probing the magnon drag scenario

We investigate Seebeck effect in REFeAsO (RE=rare earth)compounds as a function of temperature and magnetic field up to 30T. The Seebeck curves are characterized by a broad negative bump around 50K, which is sample dependent and strongly enhanced by the application of a magnetic field. A model for the temperature and field dependence of the magnon drag contribution to the Seebeck effect by antiferromagnetic (AFM) spin fluctuation is developed. It accounts for the magnitude and scaling properties of such bump feature in our experimental data. This analysis allows to extract precious information on the coupling between electrons and AFM spin fluctuations in these parent compound systems, with implications on the pairing mechanism of the related superconducting compounds

Searching for Primordial Black Holes with the Einstein Telescope: impact of design and systematics

Primordial Black Holes (PBHs) have recently attracted much attention as they may explain some of the LIGO/Virgo/KAGRA observations and significantly contribute to the dark matter in our universe. The next generation of Gravitational Wave (GW) detectors will have the unique opportunity to set stringent bounds on this putative population of objects. Focusing on the Einstein Telescope (ET), in this paper we analyse in detail the impact of systematics and different detector designs on our future capability of observing key quantities that would allow us to discover and/or constrain a population of PBH mergers. We also perform a population analysis, with a mass and redshift distribution compatible with the current observational bounds. Our results indicate that ET alone can reach an exquisite level of accuracy on the key observables considered, as well as detect up to tens of thousands of PBH binaries per year, but for some key signatures (in particular high--redshift sources) the cryogenic instrument optimised for low frequencies turns out to be crucial, both for the number of observations and the error on the parameters reconstruction. As far as the detector geometry is concerned, we find that a network consisting of two separated L--shaped interferometers of 15 (20)~km arm length, oriented at $45^{\circ}$ with respect to each other performs better than a single triangular shaped instrument of 10 (15)~km arm length, for all the metrics considered.Comment: 24 pages, 13 figure

Implementation of a sensorized neonatal head model for gynechological training

During labor it is very important to know the exact position and orientation of the fetal head when descending the birth canal. Indeed, incorrect evaluations may lead to dangerous situations for both the infant and the mother. Usually, gynecologists and midwives rely on their experience to determine the head position and to evaluate the risk level of each delivery. In this context, it is essential to train new physicians and midwives to correctly manage different types of delivery. Here, we present the design and implementation of a realistic sensorized neonatal head that could be used on low-cost birth simulators for training and evaluation of residents and midwifery students

Systematic Data Monitoring and Analysis of Cardiovascular Off-label Prescriptions in Pediatrics: Focus on Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Beta Blockers

Introduction: Many efforts have been made to stimulate clinical trials (CTs) in pediatrics but most of the drugs are still authorized only in adults and used off-label in the pediatric population. Aim: To assess how widespread is the off-label prescription in Italy and to identify areas of unmet medical need by applying a model for the systematic collection and analysis of data. Methods: A study was performed using 2015 data from the Italian Medicines Utilization Monitoring Centre Health Database (OsMed). A study sample of 3,726,583 pediatric patients, was considered. Cardiovascular drugs were selected for this study. Assessment of the off-label use, the analysis of the pharmacovigilance signals, a bibliographic research and the analysis of ongoing CTs were carried out. Results: In 2015, 8,544 pediatric patients received treatment with a cardiovascular drug. Angiotensin converting enzyme inhibitors (ACE-I) followed by beta&nbsp;blockers agents are the most prescribed molecules. Eight molecules were selected and an in-depth analysis conducted. The PhV network showed only one record of adverse reaction as off-label in 2015. The results show several therapeutic areas of use in pediatrics. Conclusion: Off-label in pediatrics is largely widespread in Europe and US and our results show it is also present in Italy. Molecules selected are used off-label for therapeutic areas such as oncologic, hematological and rare diseases. Results of pharmacovigilance suggests underreporting. The analysis carried out in this study could be an open track for a systematic monitoring activity and of interest for prescribers, pediatricians and other healthcare professionals during the clinical practice

Case Report: REL-1017 Reduces Abnormal Clinician Administered Dissociative States Scale Scores in Patients with Major Depressive Disorder

BACKGROUND: Dissociative symptoms may be found in a subset of patients with major depressive disorders (MDD). The Clinician-Administered Dissociative States Scale (CADSS) is a 23-item scale for the measurement of present-state dissociative symptoms with good inter-rater reliability and construct validity that can discriminate patients with dissociative disorders. The total CADSS score is derived by adding the score for each of the 23 items. A score of 4 or more on the CADSS is considered abnormal and clinically meaningful. Uncompetitive N-methyl-d-aspartic acid receptor (NMDAR) channel blockers have been proposed as a treatment for post-traumatic stress disorder (PTSD). REL-1017 is a novel, low potency, NMDAR channel blocker currently in Phase 3 studies for MDD. METHODS: This retrospective case series describes a subset of patients from a double-blind, randomized, placebo-controlled, in-patient 7-day, phase 2 trial of oral, once daily, 25&nbsp;mg (75&nbsp;mg loading dose on day 1, first dose) and 50&nbsp;mg REL-1017 (100&nbsp;mg loading dose on day 1, first dose) as an adjunctive treatment for MDD. This subset of patients was selected based on abnormal CADSS score at baseline, pre-treatment with the study drug. As part of REL-1017 safety evaluation, the CADSS was administered at four timepoints to all study patients: (a) 30 to 60&nbsp;minutes pre-treatment at baseline on day 1; (b) 2&nbsp;hours post-treatment on day 1 (after the first dose of study drug); (c) 2&nbsp;hours post-treatment on day 7 (after the last dose); and (d) prior to discharge on day 9 (2&nbsp;days after the last dose). RESULTS: Among the 62 randomized patients, four patients had a CADSS score of at least 4 on day 1 before study drug administration (2 patients in the 25&nbsp;mg arm [CADSS score 22 and 4]; 1 patient in the 50&nbsp;mg arm [CADSS score 35]; 1 patient in the placebo arm [CADSS score 6]). Among these 4 patients, starting on day 1, 2&nbsp;hours post-treatment, the 2 subjects in the 25&nbsp;mg subgroup (75&nbsp;mg loading dose) and 1 subject in the 50&nbsp;mg subgroup (100&nbsp;mg loading dose) showed a clinically meaningful decrease in their CADSS score, while the single patient in the placebo group showed no change. CADSS scores on Day 1 pre-treatment, day 1 post-treatment, day 7 post last treatment, and on day 9 prior to discharge were 22-2-6-0; 4-0-0-0; 35-14-9-0, and 6-6-n/a-n/a, for the two patients in the 25&nbsp;mg REL-1017 subgroup, the single patient in the 50&nbsp;mg REL-1017 subgroup, and the single patient in the placebo group, respectively. CONCLUSIONS: These retrospective case report data potentially signal that REL-1017 may determine rapid and sustained improvement in patients with MDD and concurrent clinically meaningful dissociative symptoms assessed by a CADSS score of 4 or above. Ongoing phase 3 trials with REL-1017 are expected to enroll a total of 1200 outpatients with MDD. These studies will potentially generate additional data that may support the initiation of controlled studies with REL-1017 for the treatment of PTSD. FUNDING: Relmada Therapeutics