No recombination of mtDNA after heteroplasmy for 50 generations in the mouse maternal germline

Peer reviewe

Primary Hyperparathyroidism Influences the Expression of Inflammatory and Metabolic Genes in Adipose Tissue

Background: Primary hyperparathyroidism (PHPT) is characterised by increased production of parathyroid hormone (PTH) resulting in elevated serum calcium levels. The influence on bone metabolism with altered bone resorption is the most studied clinical condition in PHPT. In addition to this, patients with PHPT are at increased risk of non-skeletal diseases, such as impaired insulin sensitivity, arterial hypertension and increased risk of death by cardiovascular diseases (CVD), possibly mediated by a chronic low-grade inflammation. The aim of this study was to investigate whether adipose tissue reflects the low-grade inflammation observed in PHPT patients. Methodology/Principal Findings: Subcutaneous fat tissue from the neck was sampled from 16 non-obese patients with PHPT and from 16 patients operated for benign thyroid diseases, serving as weight-matched controls. RNA was extracted and global gene expression was analysed with Illumina BeadArray Technology. We found 608 differentially expressed genes (q-value,0.05), of which 347 were up-regulated and 261 were down-regulated. Gene ontology analysis showed that PHPT patients expressed increased levels of genes involved in immunity and defense (e.g. matrix metallopeptidase 9, S100 calcium binding protein A8 and A9, CD14, folate receptor 2), and reduced levels of genes involved in metabolic processes. Analysis of transcription factor binding sites present in the differentially expressed genes corroborated the up-regulation of inflammatory processes. Conclusions/Significance: Our findings demonstrate that PHPT strongly influences gene regulation in fat tissue, which may result in altered adipose tissue function and release of pathogenic factors that increase the risk of CVD

Improving the simulation framework for the CERN Beam Gas Ionisation profile monitor instruments

Virtual-IPM is a simulation software written in Python to simulate the behaviour of Beam Gas Ionisation (BGI) profile monitors , developed for the IPMSim collaboration. Although an incredibly powerful tool it lacks some features, thus the goal of this project was to try and implement some of these. The implementations were particle generation along the longitudinal axis (z-axis) which includes two new particle generation models. An option to simulate DC beams with Gaussian transverse distribution and a tool to plot the electric field from the configuration file. Basic support for design exploration/optimization that allows the user to change specific parameters slightly and generate multiple configuration files with these changes. All implementations have been tested and was added to the release of V2.

URClearED - Defining the Remain Well Clear concept for airspace D-G classes in the European airspace

Remotely Piloted Aircraft Systems (RPAS) are increasingly becoming a part of our day-to-day life, and the wide range of their possible applications is creating a new industry with a large economic potential that is pushing the technological developments at a much faster pace than that for manned aviation. However, due to constraints arising from safety and operational considerations, RPAS can currently only fly in segregated airspace, making their integration in the civil airspace an unsolved challenge. RPAS have to guarantee a level of safety at least equal to that of manned aircraft. Manned aviation follows the rules of the air. The notion "well-clear" is used in ICAO rules without giving exact definition of the term. Here, rules rely on the perception and judgement of the pilot. The capability to perform RWC and DAA is required for the full integration of RPAS with General Air Traffic (GAT). To this end, several rule-making bodies are working to define the required safety and performance objectives. An RPAS needs proper mathematical definitions of Remain-Well-Clear (RWC) in order to operate safely. When implementing RPAS into civil airspace, exact well-clear parameters have to be determined. In 2013, the second FAA workshop on Unmanned Aerial Systems (UAS) concluded that "there is a need for establishing an unambiguous and quantitative definition for well clear that can be used as a separation performance standard for an aircraft system". In 2014, the SAA Science and Research Panel (SARP) provided a Well Clear Recommendation to RTCA SC-228, which was subsequently used in the first Minimum Operational Performance Standards for Detect and Avoid (DAA) systems, DO-365. The URClearED project intends to define the requirements and capabilities for the RWC function of a DAA system of an RPAS operating in Class D-G airspace also interacting with VFR flights. Particularly in airspace classes F-G IFR aircraft will not receive ATC-provided separation. Different European countries may define airspace classes and rules differently. Further, the congestion of the airspace and the characteristics of the VFR traffic may complicate the situation. When crossing state border airspace class and rules may change. This paper will report the definition of scenarios and use cases selected to evaluate the RWC function under the aforementioned conditions. RWC volume and threshold selection will be evaluated in a subsequent simulation and assessment phase. Scenarios will encompass all the relevant elements under analysis. The type of encounter are a primary factor, not only in terms of its geometry but also in terms of the rules under which the conflicting aircraft are operating and the specific airspace classes involved. This will impact the roles and responsibilities of involved actors. Transitions between different classes of airspace will also be considered, including states cross-border situations

URClearED – Defining the remain well clear concept for airspace D-G classes in the European airspace

Remotely Piloted Aircraft Systems (RPAS) are increasingly becoming a part of our day-to-day life, and the wide range of their possible applications is creating a new industry with a large economic potential that is pushing the technological developments at a much faster pace than that for manned aviation. However, due to constraints arising from safety and operational considerations, RPAS can currently only fly in segregated airspace, making their integration in the civil airspace an unsolved challenge. RPAS have to guarantee a level of safety at least equal to that of manned aircraft. Manned aviation follows the rules of the air. The notion “well-clear” is used in ICAO rules without giving exact definition of the term. Here, rules rely on the perception and judgement of the pilot. The capability to perform RWC and DAA is required for the full integration of RPAS with General Air Traffic (GAT). To this end, several rule-making bodies are working to define the required safety and performance objectives. An RPAS needs proper mathematical definitions of Remain-Well-Clear (RWC) in order to operate safely. When implementing RPAS into civil airspace, exact well-clear parameters have to be determined. In 2013, the second FAA workshop on Unmanned Aerial Systems (UAS) concluded that ‘there is a need for establishing an unambiguous and quantitative definition for well clear that can be used as a separation performance standard for an aircraft system’. In 2014, the SAA Science and Research Panel (SARP) provided a Well Clear Recommendation to RTCA SC-228, which was subsequently used in the first Minimum Operational Performance Standards for Detect and Avoid (DAA) systems, DO-365. The URClearED project intends to define the requirements and capabilities for the RWC function of a DAA system of an RPAS operating in Class D-G airspace also interacting with VFR flights. Particularly in airspace classes F-G IFR aircraft will not receive ATC-provided separation. Different European countries may define airspace classes and rules differently. Further, the congestion of the airspace and the characteristics of the VFR traffic may complicate the situation. When crossing state border airspace class and rules may change. This paper will report the definition of scenarios and use cases selected to evaluate the RWC function under the aforementioned conditions. RWC volume and threshold selection will be evaluated in a subsequent simulation and assessment phase. Scenarios will encompass all the relevant elements under analysis. The type of encounter are a primary factor, not only in terms of its geometry but also in terms of the rules under which the conflicting aircraft are operating and the specific airspace classes involved. This will impact the roles and responsibilities of involved actors. Transitions between different classes of airspace will also be considered, including states cross-border situations. © 2021, American Institute of Aeronautics and Astronautics Inc.. All rights reserved.This project has received funding from the SESAR Joint Undertaking (JU) under grant agreement No 892440. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and the SESAR JU members other than the Union. This paper only reflects the author’s views and the SESAR JU is not responsible for any use that may be made of the information it contains.Peer ReviewedPostprint (published version

Incidence, prevalence and mortality of chronic liver diseases in Sweden between 2005 and 2019

BackgroundUpdated data on the incidence, prevalence, and regional differences of chronic liver disease are missing from many countries. In this study, we aimed to describe time trends, incidence, prevalence, and mortality of a wide range of chronic liver diseases in Sweden.MethodsIn this register-based, nationwide observational study, patients with a register-based diagnosis of chronic liver disease, during 2005-2019, were retrieved from the Swedish National Board of Health and Welfare. Annual age-standardized incidence and mortality rates, and prevalence per 100,000 inhabitants was calculated and stratified on age, sex, and geographical region.ResultsThe incidence of alcohol-related cirrhosis increased by 47% (2.6% annually), reaching an incidence rate of 13.1/100,000 inhabitants. The incidence rate of non-alcoholic fatty liver disease and unspecified liver cirrhosis increased by 217% and 87% (8.0 and 4.3% annually), respectively, reaching an incidence rate of 15.2 and 18.7/100,000 inhabitants, and a prevalence of 24.7 and 44.8/100,000 inhabitants. Furthermore, incidence rates of chronic hepatitis C declined steeply, but liver malignancies have become more common. The most common causes of liver-related mortality were alcohol-related liver disease and unspecified liver disease.ConclusionThe incidence rates of diagnosed non-alcoholic fatty liver disease, alcohol-related cirrhosis, unspecified liver cirrhosis, and liver malignancies have increased during the last 15 years. Worryingly, mortality in several liver diseases increased, likely reflecting increasing incidences of cirrhosis in spite of a decreasing rate of hepatitis C. Significant disparities exist across sex and geographical regions, which need to be considered when allocating healthcare resources.Funding Agencies|Karolinska Institute; ALF Grants, Region OEstergoetland; Lion Research Grant, Faculty of Medicine, Linkoeping University; Region Stockholm; Swedish Cancer Society; Swedish Research Council</p

Molecular Diagnosis of Hemorrhagic Fever with Renal Syndrome Caused by Puumala Virus

Rodent-borne hantaviruses cause two severe acute diseases: hemorrhagic fever with renal syndrome (HFRS) in Eurasia, and hantavirus pulmonary syndrome (HPS; also called hantavirus cardiopulmonary syndrome [HCPS]) in the Americas. Puumala virus (PUUV) is the most common causative agent of HFRS in Europe. Current routine diagnostic methods are based on serological analyses and can yield inconclusive results. Hantavirus-infected patients are viremic during the early phase of disease; therefore, detection of viral RNA genomes can be a valuable complement to existing serological methods. However, the high genomic sequence diversity of PUUV has hampered the development of molecular diagnostics, and currently no real-time reverse transcription- quantitative (RT)-PCR assay is available for routine diagnosis of HFRS. Here, we present a novel PUUV RT-PCR assay. The assay was validated for routine diagnosis of HFRS on samples collected in Sweden during the winter season from 2013 to 2014. The assay allowed detection of PUUV RNA in 98.7% of confirmed clinical HFRS samples collected within 8 days after symptomatic onset. In summary, this study shows that real-time RT-PCR can be a reliable alternative to serological tests during the early phase of HFRS