EFFECT OF FORMING PRESSURE ON THE REACTIVITY AND MICROSTRUCTURE OF ZIRCON POWDER COMPACTS

Preliminary results of a study on the effects of the forming pressure on the reactivity, sintering and microstructure of very fine natural zircon powder compacts. The effects of compaction pressure on the green densities and sintered densities are also discussed. The relationship between the density and the compaction pressure governs the mechanism that occurs in the consolidation process. The investigation has demonstrated changing the compaction pressure in the range 45-180MPa does not influence the onset temperature of sintering of powdered zircon (1150-1170 °C) but does influence the apparent density of the green compacts and consequently the porosity of the sintered specimens. Low relative density values were obtained in these sintering conditions

Exploring the data on femicide across Europe

In recent years, the notion of femicide has expanded in social, criminological and epidemiological research to grasp the basic differences underpinning the killing of a female, as opposed to a male, victim. While femicide research in Australia and the US has been a consolidated trend in criminology and feminist studies since the 1990s (Stout, 1992; Mouzos, 1999; Campbell et al, 2003; Frye et al, 2005), its development in Europe has been much more recent and represents the outcome, primarily, of top-down social pressure. The combined effect of the recent proceedings of the ‘Femicide across Europe’ COST network (active in 30 European countries from 2013 to 2017), together with awareness-raising by the media in many countries and the Resolution adopted by the United Nations General Assembly on 11 February 2014 (United Nations, 2014), inter alia, have acted as catalysts for change, contributing significantly to fostering femicide research in Europe. An extensive analysis of the definition of femicide is presented in Chapter 2 of this book.peer-reviewe

Progress of Induced Pluripotent Stem Cell Technologies to Understand Genetic Epilepsy

The study of the pathomechanisms by which gene mutations lead to neurological diseases has benefit from several cellular and animal models. Recently, induced Pluripotent Stem Cell (iPSC) technologies have made possible the access to human neurons to study nervous system disease-related mechanisms, and are at the forefront of the research into neurological diseases. In this review, we will focalize upon genetic epilepsy, and summarize the most recent studies in which iPSC-based technologies were used to gain insight on the molecular bases of epilepsies. Moreover, we discuss the latest advancements in epilepsy cell modeling. At the two dimensional (2D) level, single-cell models of iPSC-derived neurons lead to a mature neuronal phenotype, and now allow a reliable investigation of synaptic transmission and plasticity. In addition, functional characterization of cerebral organoids enlightens neuronal network dynamics in a three-dimensional (3D) structure. Finally, we discuss the use of iPSCs as the cutting-edge technology for cell therapy in epilepsy

Mmot1, a New Helix-Loop-Helix Transcription Factor Gene Displaying a Sharp Expression Boundary in the Embryonic Mouse Brain

Several genetic factors have been proven to contribute to the specification of the metencephalic-mesencephalic territory, a process that sets the developmental foundation for prospective morphogenesis of the cerebellum and mesencephalon. However, evidence stemming from genetic and developmental studies performed in man and various model organisms suggests the contribution of many additional factors in determining the fine subdivision and differentiation of these central nervous system regions. In man, the cerebellar ataxias/aplasias represent a large and heterogeneous family of genetic disorders. Here, we describe the identification by differential screening and the characterization of Mmot1, a new gene encoding a DNA-binding protein strikingly similar to the helix-loop-helix factor Ebf/Olf1. Throughout midgestation embryogenesis, Mmot1is expressed at high levels in the metencephalon, mesencephalon, and sensory neurons of the nasal cavity. In vitro DNA binding data suggest some functional equivalence of Mmot1 and Ebf/Olf1, possibly accounting for the reported lack of olfactory or neural defects in Ebf −/− knockout mutants. The isolation of Mmot1 and of an additional homolog in the mouse genome defines a novel, phylogenetically conserved mammalian family of transcription factor genes of potential relevance in studies of neural development and its aberrations

Ultrasound- versus landmark-guided subclavian vein catheterization: a prospective observational study from a tertiary referral hospital

This was a single-center, observational, prospective study designed to compare the effectiveness of a real-time, ultrasound- with landmark-guided technique for subclavian vein cannulation. Two groups of 74 consecutive patients each underwent subclavian vein catheterization. One group included patients from intensive care unit, studied by using an ultrasound-guided technique. The other group included patients from surgery or emergency units, studied by using a landmark technique. The primary outcome for comparison between techniques was the success rate of catheterization. Secondary outcomes were the number of attempts, cannulation failure, and mechanical complications. Although there was no difference in total success rate between ultrasound-guided and landmark groups (71 vs. 68, p\u2009=\u20090.464), the ultrasound-guided technique was more frequently successful at first attempt (64 vs. 30, p\u2009<\u20090.001) and required less attempts (1 to 2 vs. 1 to 6, p\u2009<\u20090.001) than landmark technique. Moreover, the ultrasound-guided technique was associated with less complications (2 vs. 13, p\u2009<\u20090.001), interruptions of mechanical ventilation (1 vs. 57, p\u2009<\u20090.001), and post-procedure chest X-ray (43 vs. 62, p\u2009=\u20090.001). In comparison with landmark-guided technique, the use of an ultrasound-guided technique for subclavian catheterization offers advantages in terms of reduced number of attempts and complications

Use of the international classification of diseases (ICD)-11 method applied to veterinary forensic pathology for coding the cause and manner of death in wildlife

The growth of human population has led, in recent years, to increasingly frequent contacts with the wild animals with which we share the territory, sometimes leading to negative interactions with them. The purpose of the study is to apply the codes contained in the 11th Revision of the International Classification of Diseases (ICD-11) method to investigate the cause and the manner of death, also to entrust the veterinarian with the task of recognizing and describing a suspected animal abuse as a sentinel indicator of violence toward humans and non-humans, thus expanding the concept of “One Health” from a forensic investigation perspective. The subjects recruited are wild mammals submitted for autopsy to the Pathology Unit of the Department of Veterinary Science, University of Parma, Italy, from 2015 to 2018. The manner and the cause of death of 167 wild animals of 16 different species have been investigated. When possible, an on-site inspection where the corpse was found was performed. Injuries were classified according to the on-line 11th Revision of the International Classification of Diseases method. Section 22 (Injury, poisoning or certain other consequences of external causes) was used to record the “immediate cause of death” (cause of death) and Section 23 (External causes of morbidity or mortality) was used to record the “underlying cause of death” (manner of death) for each animal. In most cases, death occurred as a result of road trauma but in some cases, abuse and voluntary killing were investigated. The recognition of non-accidental injuries is particularly important for both the defense in court of animals and for the connection between crimes committed against animals and against humans, known as “The Link”. The use of the ICD-11 method, as a sort of summary of the autopsy report, was confirmed to be of great value for the clarity and simplicity of processing the data collected also by veterinary pathologists. The veterinary pathologists can use this evidence-based method with the aim of creating a national register and therefore, to understand the real extent of the human impact on wildlife and document it in a scientific and statistically usable way

MEK1/2 regulate normal BCR and ABL1 tumor-suppressor functions to dictate ATO response in TKI-resistant Ph+ leukemia

Resistance to tyrosine kinase inhibitors (TKIs) remains a clinical challenge in Ph-positive variants of chronic myeloid leukemia. We provide mechanistic insights into a previously undisclosed MEK1/2/BCR::ABL1/BCR/ABL1-driven signaling loop that may determine the efficacy of arsenic trioxide (ATO) in TKI-resistant leukemic patients. We find that activated MEK1/2 assemble into a pentameric complex with BCR::ABL1, BCR and ABL1 to induce phosphorylation of BCR and BCR::ABL1 at Tyr360 and Tyr177, and ABL1, at Thr735 and Tyr412 residues thus provoking loss of BCR's tumor-suppression functions, enhanced oncogenic activity of BCR::ABL1, cytoplasmic retention of ABL1 and consequently drug resistance. Coherently, pharmacological blockade of MEK1/2 induces dissociation of the pentameric MEK1/2/BCR::ABL1/BCR/ABL1 complex and causes a concurrent BCRY360/Y177, BCR::ABL1Y360/Y177 and cytoplasmic ABL1Y412/T735 dephosphorylation thereby provoking the rescue of the BCR's anti-oncogenic activities, nuclear accumulation of ABL1 with tumor-suppressive functions and consequently, growth inhibition of the leukemic cells and an ATO sensitization via BCR-MYC and ABL1-p73 signaling axes activation. Additionally, the allosteric activation of nuclear ABL1 was consistently found to enhance the anti-leukemic effects of the MEK1/2 inhibitor Mirdametinib, which when combined with ATO, significantly prolonged the survival of mice bearing BCR::ABL1-T315I-induced leukemia. These findings highlight the therapeutic potential of MEK1/2-inhibitors/ATO combination for the treatment of TKI-resistant leukemia

Issues in measuring and comparing the incidence of intimate partner homicide and femicide - A focus on Europe

Intimate partner homicide is an important contributor to homicide rates worldwide, disproportionally affecting women as victims. Still, major gaps exist in the measurement of intimate partner homicide, with many homicides not being identified as intimate partner homicides. This article provides an overview of the main issues in the collection and reporting on intimate partner homicide, focusing in particular on the data situation in Europe. Sources of homicide data - national and police statistics, court statistics and files, mortuary data and newspaper databases - face similar challenges, namely absence or missing information on the victim-offender relationship, and different categorizations of key parameters, such as definition of intimate partner homicide, and identification of reporting periods. This is concerning, as strong and reliable data on the incidence and contextual information of intimate partner homicide and femicide is important to advice effective prevention strategies