The WHO QualityRights initiative: Building partnerships among psychiatrists, people with lived experience and other key stakeholders to improve the quality of mental healthcare

Psychiatrists have an essential role to play in promoting human rights in mental healthcare. The World Health Organization's QualityRights initiative, in partnership with different stakeholders, is improving the quality of psychiatric care in different countries

EAIMS: Emergency Analysis Identification and Management System

Social media has great potential as a means to enable civil protection and law enforcement agencies to more effectively tackle disasters and emergencies. However, there is currently a lack of tools that enable civil protection agencies to easily make use of social media. The Emergency Analysis Identification and Management System (EAIMS) is a prototype service that provides real-time detection of emergency events, related information finding and credibility analysis tools for use over social media during emergencies. This system exploits machine learning over data gathered from past emergencies and disasters to build effective models for identifying new events as they occur, tracking developments within those events and analyzing those developments for the purposes of enhancing the decision making processes of emergency response agencies

Medial septal beta-amyloid 1-40 injections alter septo-hippocampal anatomy and function

Degeneration of septal neurons in Alzheimer’s disease (AD) results in abnormal information processing at cortical circuits and consequent brain dysfunction. The septum modulates the activity of hippocampal and cortical circuits and is crucial to the initiation and occurrence of oscillatory activities such as the hippocampal theta rhythm. Previous studies suggest that amyloid β peptide (Aβ) accumulation may trigger degeneration in AD. This study evaluates the effects of single injections of Aβ 1–40 into the medial septum. Immunohistochemistry revealed a decrease in septal cholinergic (57%) and glutamatergic (53%) neurons in Aβ 1–40 treated tissue. Additionally, glutamatergic terminals were significantly less in Aβ treated tissue. In contrast, septal GABAergic neurons were spared. Unitary recordings from septal neurons and hippocampal field potentials revealed an approximately 50% increase in firing rates of slow firing septal neurons during theta rhythm and large irregular amplitude (LIA) hippocampal activities and a significantly reduced hippocampal theta rhythm power (49%) in Aβ 1–40 treated tissue. Aβ also markedly reduced the proportion of slow firing septal neurons correlated to the hippocampal theta rhythm by 96%. These results confirm that Aβ alters the anatomy and physiology of the medial septum contributing to septohippocampal dysfunction. The Aβ induced injury of septal cholinergic and glutamatergic networks may contribute to an altered hippocampal theta rhythm which may underlie the memory loss typically observed in AD patients

Niosomes based on synthetic cationic lipids for gene delivery: The influence of polar head-groups on the transfection efficiency in HEK-293, ARPE-19 and MSC-D1 cells

We designed niosomes based on three lipids that differed only in the polar-head group to analyze their influence on the transfection efficiency. These lipids were characterized by small-angle X-ray scattering before being incorporated into the niosomes which were characterized in terms of pKa, size, zeta potential, morphology and physical stability. Nioplexes were obtained upon the addition of a plasmid. Different ratios (w/w) were selected to analyze the influence of this parameter on size, charge and the ability to condense, release and protect the DNA. In vitro transfection experiments were performed in HEK-293, ARPE-19 and MSC-D1 cells. Our results show that the chemical composition of the cationic head-group clearly affects the physicochemical parameters of the niosomes and especially the transfection efficiency. Only niosomes based on cationic lipids with a dimethyl amino head group (lipid 3) showed a transfection capacity when compared with their counterparts amino (lipid 1) and tripeptide head-groups (lipid 2). Regarding cell viability, we clearly observed that nioplexes based on the cationic lipid 3 had a more deleterious effect than their counterparts, especially in ARPE-19 cells at 20/1 and 30/1 ratios. Similar studies could be extended to other series of cationic lipids in order to progress in the research on safe and efficient non-viral vectors for gene delivery purposes.This project was partially supported by the University of the Basque Country UPV/EHU (UFI 11/32), the National Council of Science and Technology (CONAYT), Mexico, Reg. # 217101, the Spanish Ministry of Education (Grant CTQ2010-20541, CTQ2010-14897), the Basque Government (Department of Education, University and Research, predoctoral BFI-2011-2226 grant), the Generalitat de Catalunya (2009SGR208, 2009SGR1331) and the Instituto de Salud Carlos III. Technical and human support provided by SGIker (UPV/EHU) is gratefully acknowledged. Authors also wish to thank the intellectual and technical assistance from the platform for Drug Formulation (NANBIOSIS) CIBER-BBN.Peer reviewe

The influence of the polar head-group of synthetic cationic lipids on the transfection efficiency mediated by niosomes in rat retina and brain

The development of novel non-viral delivery vehicles is essential in the search of more efficient strategies for retina and brain diseases. Herein, optimized niosome formulations prepared by oil-in water (o/w) and film-hydration techniques were characterized in terms of size, PDI, zeta potential, morphology and stability. Three ionizable glycerol-based cationic lipids containing a primary amine group (lipid 1), a triglycine group (lipid 2) and a dimethylamino ethyl pendent group (lipid 3) as polar head-groups were part of such niosomes. Upon the addition of pCMS-EGFP plasmid, nioplexes were obtained at different cationic lipid/DNA ratios (w/w). The resultant nioplexes were further physicochemically characterized and evaluated to condense, release and protect the DNA against enzymatic digestion. In vitro experiments were performed to evaluate transfection efficiency and cell viability in HEK-293, ARPE-19 and PECC cells. Interestingly, niosome formulations based on lipid 3 showed better transfection efficiencies in ARPE-19 and PECC cells than the rest of cationic lipids showed in this study. In vivo experiments in rat retina after intravitreal and subretinal injections together with in rat brain after cerebral cortex administration showed promising transfection efficiencies when niosome formulations based on lipid 3 were used. These results provide new insights for the development of non-viral vectors based on cationic lipids and their applications for efficient delivery of genetic material to the retina and brain. © 2015 Elsevier Ltd.This project was partially supported by the University of the Basque Country UPV/EHU (UFI 11/32), the National Council of Science and Technology (CONACYT), Mexico, Reg. # 217101, the Spanish Ministry of Education (Grant CTQ2010-20541, CTQ2010- 14897), the Basque Government (Department of Education, University and Research, predoctoral BFI-2011-2226 grant) and by Spanish grants MAT2012-39290-C02-01 and IPT-2012-0574- 300000. Technical and human support provided by SGIker (UPV/ EHU) is gratefully acknowledged. Authors also wish to thank the intellectual and technical assistance from the ICTS “NANBIOSIS”, more specifically by the Drug Formulation Unit (U10) of the CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN) at the University of Basque Country (UPV/EHU).Peer reviewe

The IMERAPlus Joint Research Project For Determinations Of The Boltzmann Constant

Abstract. To provide new determinations of the Boltzmann constant, k, which has been asked for by the International Committee for Weights and Measures concerning preparative steps towards new definitions of the kilogram, the ampere, the kelvin and the mole, an iMERAPlus joint research project has coordinated the European activities in this field. In this major European research project the Boltzmann constant has been determined by various methods to support the new definition of the kelvin. The final results of the project are reviewed in this paper. Determinations of the Boltzmann constant k were achieved within the project by all three envisaged methods: acoustic gas thermometry, Doppler broadening technique, and dielectric constant gas thermometry. The results were exploited by the interdisciplinary Committee on Data for Science and Technology (CODATA) in their 2010 adjustment of recommended values for fundamental constants. As a result, the CODATA group recommended a value for k with a relative standard uncertainty about a factor of two smaller than the previous u(k)/k of 1.7×10 −6

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality