Polymorphic inverted repeats near coding genes impact chromatin topology and phenotypic traits in Arabidopsis thaliana

Transposons are mobile elements that are commonly silenced to protect eukaryotic genome integrity. In plants, transposable element (TE)-derived inverted repeats (IRs) are commonly found near genes, where they affect host gene expression. However, the molecular mechanisms of such regulation are unclear in most cases. Expression of these IRs is associated with production of 24-nt small RNAs, methylation of the IRs, and drastic changes in local 3D chromatin organization. Notably, many of these IRs differ between Arabidopsis thaliana accessions, causing variation in short-range chromatin interactions and gene expression. CRISPR-Cas9-mediated disruption of two IRs leads to a switch in genome topology and gene expression with phenotypic consequences. Our data show that insertion of an IR near a gene provides an anchor point for chromatin interactions that profoundly impact the activity of neighboring loci. This turns IRs into powerful evolutionary agents that can contribute to rapid adaptation

Evaluation of an integrated system for classification, assessment and comparison of services for long-term care in Europe: the eDESDE-LTC study

The harmonization of European health systems brings with it a need for tools to allow the standardized collection of information about medical care. A common coding system and standards for the description of services are needed to allow local data to be incorporated into evidence-informed policy, and to permit equity and mobility to be assessed. The aim of this project has been to design such a classification and a related tool for the coding of services for Long Term Care (DESDE-LTC), based on the European Service Mapping Schedule (ESMS). Methods. The development of DESDE-LTC followed an iterative process using nominal groups in 6 European countries. 54 researchers and stakeholders in health and social services contributed to this process. In order to classify services, we use the minimal organization unit or "Basic Stable Input of Care" (BSIC), coded by its principal function or "Main Type of Care" (MTC). The evaluation of the tool included an analysis of feasibility, consistency, ontology, inter-rater reliability, Boolean Factor Analysis, and a preliminary impact analysis (screening, scoping and appraisal). Results: DESDE-LTC includes an alpha-numerical coding system, a glossary and an assessment instrument for mapping and counting LTC. It shows high feasibility, consistency, inter-rater reliability and face, content and construct validity. DESDE-LTC is ontologically consistent. It is regarded by experts as useful and relevant for evidence-informed decision making. Conclusion: DESDE-LTC contributes to establishing a common terminology, taxonomy and coding of LTC services in a European context, and a standard procedure for data collection and international comparison

Bronchial responses to substance P after antigen challenge in the guinea-pig: in vivo and in vitro studies

The effect of antigen challenge on the airway responses to substance P and on the epithelial neutral endopeptidase (NEP) activity was investigated in aerosol sensitized guinea-pigs. In vivo, bronchial responses to aerosolized substance P were similar to the responses observed in antigen-challenged guinea-pigs and in the control groups. In contrast, when the guinea-pigs were pretreated with the NEP inhibitor, phosphoramidon, a significant increase in the airway responses to substance P was observed after antigen challenge in vivo. However, in vitro, the contractile responses of the tracheal smooth muscle to substance P were similar between groups of guinea-pigs, in respect to the presence or absence of the epithelium and/or phosphoramidon. Histological studies showed an accumulation of eosinophils in the tracheal submucosa after antigen challenge and intact epithelial cells. These results show that in vivo bronchial hyperresponsiveness to substance P after antigen challenge in the guinea-pig is not associated with increased responses of the smooth muscle to exogenous SP in vitro. In addition, the results with phosphoramidon suggest that loss of NEP activity cannot account for the in vivo bronchial hyperresponsiveness to substance P presently observed

Modelling the balance of care:Impact of an evidence-informed policy on a mental health ecosystem

Major efforts worldwide have been made to provide balanced Mental Health (MH) care. Any integrated MH ecosystem includes hospital and community-based care, highlighting the role of outpatient care in reducing relapses and readmissions. This study aimed (i) to identify potential expert-based causal relationships between inpatient and outpatient care variables, (ii) to assess them by using statistical procedures, and finally (iii) to assess the potential impact of a specific policy enhancing the MH care balance on real ecosystem performance. Causal relationships (Bayesian network) between inpatient and outpatient care variables were defined by expert knowledge and confirmed by using multivariate linear regression (generalized least squares). Based on the Bayesian network and regression results, a decision support system that combines data envelopment analysis, Monte Carlo simulation and fuzzy inference was used to assess the potential impact of the designed policy. As expected, there were strong statistical relationships between outpatient and inpatient care variables, which preliminarily confirmed their potential and a priori causal nature. The global impact of the proposed policy on the ecosystem was positive in terms of efficiency assessment, stability and entropy. To the best of our knowledge, this is the first study that formalized expert-based causal relationships between inpatient and outpatient care variables. These relationships, structured by a Bayesian network, can be used for designing evidence-informed policies trying to balance MH care provision. By integrating causal models and statistical analysis, decision support systems are useful tools to support evidence-informed planning and decision making, as they allow us to predict the potential impact of specific policies on the ecosystem prior to its real application, reducing the risk and considering the population’s needs and scientific findings

Clarifying terminology and definitions in education services for mental health users:A disambiguation study

In the wake of the mental health crisis in children and adolescents, the coordination of education and mental health services has become a global priority. However, differing terminologies and classifications across sectors, hinder effective comparison. The classification in education focuses mainly on outputs like qualifications or throughputs like teaching programs. This proof-of-concept study tested the applicability of a standard classification of health services, the Description and Evaluation of Services and DirectoriEs (DESDE), to evaluate education services for mental health users in the context of Spain and The Netherlands. It was conducted alongside the PECUNIA project, that sought to develop methods for the assessment of mental health costs and outcomes in different sectors. The study followed an ontoterminology approach involving: 1) identification of services from a predefined list of 46 resource-use items, 2) disambiguation of identified services with the DESDE, and classifying them as accurate, ambiguous, vague or confuse; and 3) external validation by an expert panel. The analysis was conducted at the level of type of resource, target population and care provision. From the initial list, only ten of the resources could be categorized as services using DESDE, and not activities, interventions or professionals. Only four of them (8,65%) were accurate across all disambiguation categories. Experts were unaware of terminology problems in classification of service provision in the education sector. Classifications and glossaries can clarify service naming, description and costing allowing comparative effectiveness analysis and facilitating cross-sectoral planning. This should be grounded in common methodologies, tools, and units of analysis

Clarifying terminology and definitions in education services for mental health users:A disambiguation study

In the wake of the mental health crisis in children and adolescents, the coordination of education and mental health services has become a global priority. However, differing terminologies and classifications across sectors, hinder effective comparison. The classification in education focuses mainly on outputs like qualifications or throughputs like teaching programs. This proof-of-concept study tested the applicability of a standard classification of health services, the Description and Evaluation of Services and DirectoriEs (DESDE), to evaluate education services for mental health users in the context of Spain and The Netherlands. It was conducted alongside the PECUNIA project, that sought to develop methods for the assessment of mental health costs and outcomes in different sectors. The study followed an ontoterminology approach involving: 1) identification of services from a predefined list of 46 resource-use items, 2) disambiguation of identified services with the DESDE, and classifying them as accurate, ambiguous, vague or confuse; and 3) external validation by an expert panel. The analysis was conducted at the level of type of resource, target population and care provision. From the initial list, only ten of the resources could be categorized as services using DESDE, and not activities, interventions or professionals. Only four of them (8,65%) were accurate across all disambiguation categories. Experts were unaware of terminology problems in classification of service provision in the education sector. Classifications and glossaries can clarify service naming, description and costing allowing comparative effectiveness analysis and facilitating cross-sectoral planning. This should be grounded in common methodologies, tools, and units of analysis

Clarifying terminology and definitions in education services for mental health users: A disambiguation study

In the wake of the mental health crisis in children and adolescents, the coordination of education and mental health services has become a global priority. However, differing terminologies and classifications across sectors, hinder effective comparison. The classification in education focuses mainly on outputs like qualifications or throughputs like teaching programs. This proof-of-concept study tested the applicability of a standard classification of health services, the Description and Evaluation of Services and DirectoriEs (DESDE), to evaluate education services for mental health users in the context of Spain and The Netherlands. It was conducted alongside the PECUNIA project, that sought to develop methods for the assessment of mental health costs and outcomes in different sectors. The study followed an ontoterminology approach involving: 1) identification of services from a predefined list of 46 resource-use items, 2) disambiguation of identified services with the DESDE, and classifying them as accurate, ambiguous, vague or confuse; and 3) external validation by an expert panel. The analysis was conducted at the level of type of resource, target population and care provision. From the initial list, only ten of the resources could be categorized as services using DESDE, and not activities, interventions or professionals. Only four of them (8,65%) were accurate across all disambiguation categories. Experts were unaware of terminology problems in classification of service provision in the education sector. Classifications and glossaries can clarify service naming, description and costing allowing comparative effectiveness analysis and facilitating cross-sectoral planning. This should be grounded in common methodologies, tools, and units of analysis

A new bottom-up method for the standard analysis and comparison of workforce capacity in mental healthcare planning: Demonstration study in the Australian Capital Territory

The aims of this study are to evaluate and describe mental health workforce and capacity, and to describe the relationship between workforce capacity and patterns of care in local areas. We conducted a comparative demonstration study of the applicability of an internationally validated standardised service classification instrument—the Description and Evaluation of Services and Directories—DESDE-LTC) using the emerging mental health ecosystems research (MHESR) approach. Using DESDE-LTC as the framework, and drawing from international occupation classifications, the workforce was classified according to characteristics including the type of care provided and professional background. Our reference area was the Australian Capital Territory, which we compared with two other urban districts in Australia (Sydney and South East Sydney) and three benchmark international health districts (Helsinki-Uusima (Finland), Verona (Italy) and Gipuzkoa (Spain)). We also compared our data with national level data where available. The Australian and Finnish regions had a larger and more highly skilled workforce than the southern European regions. The pattern of workforce availability and profile varied, even within the same country, at the local level. We found significant differences between regional rates of identified rates of psychiatrists and psychologists, and national averages. Using a standardised classification instrument at the local level, and our occupational groupings, we were able to assess the available workforce and provide information relevant to planners about the actual capacity of the system. Data obtained at local level is critical to providing planners with reliable data to inform their decision making.This research is supported by the Bupa Foundation

A Comparison of Mental Health Care Systems in Northern and Southern Europe : A Service Mapping Study

Mental health services (MHS) have gone through vast changes during the last decades, shifting from hospital to community-based care. Developing the optimal balance and use of resources requires standard comparisons of mental health care systems across countries. This study aimed to compare the structure, personnel resource allocation, and the productivity of the MHS in two benchmark health districts in a Nordic welfare state and a southern European, family-centered country. The study is part of the REFINEMENT (Research on Financing Systems' Effect on the Quality of Mental Health Care) project. The study areas were the Helsinki and Uusimaa region in Finland and the Girona region in Spain. The MHS were mapped by using the DESDE-LTC (Description and Evaluation of Services and Directories for Long Term Care) tool. There were 6.7 times more personnel resources in the MHS in Helsinki and Uusimaa than in Girona. The resource allocation was more residential-service-oriented in Helsinki and Uusimaa. The difference in mental health personnel resources is not explained by the respective differences in the need for MHS among the population. It is important to make a standard comparison of the MHS for supporting policymaking and to ensure equal access to care across European countries.Peer reviewe

Fluxonium Qubits in a Flip-Chip Package

The strong anharmonicity and high coherence times inherent to fluxonium superconducting circuits are beneficial for quantum information processing. In addition to requiring high-quality physical qubits, a quantum processor needs to be assembled in a manner that minimizes crosstalk and decoherence. In this paper, we report work on fluxonium qubits packaged in a flip-chip architecture, where a classical control and readout chip is bump-bonded to the quantum chip, forming a multi-chip module (MCM). The modular approach allows for improved connectivity between the qubits and control/readout elements, and separate fabrication processes. We characterize the coherence properties of the individual fluxonium qubits, demonstrate high fidelity single-qubit gates with 6 ns microwave pulses (without DRAG), and identify the main decoherence mechanisms to improve on the reported results