Innovationsprozesse wissensbasierter Technologien : Beispiel der PEM-Brennstoffzelle

Wissen zeichnet sich zunehmend als entscheidender Produktionsfaktor ab und bildet die Basis für Entwicklungen wissensbasierter Technologien. Diese Untersuchung analysiert am Beispiel der PEM-Brennstoffzellentechnologie diesen Innovationsprozess und bedient sich dazu der Heuristik des Innovationssystems. Gleichzeitig wird ein detailiertes Bild der PEM-Technologie als Teil der Elektromobilität gezeichnet

Estimating environmental exposure to analgesic drugs: A cross-sectional study of drug utilization patterns in the area surrounding Sweden’s largest drinking water source

Use of pharmaceuticals is continuously increasing globally and their residues are recognized as a risk for the environment. The aim of this study was to investigate drug utilization patterns of analgesics in relation to environmental hazard in the region surrounding Sweden's largest drinking water source, Lake Mälaren. This was examined using sales data on pharmaceuticals from the Swedish E-health Agency. The total sales of analgesics (non-steroidal anti-inflammatory drugs, paracetamol, other non-opioid analgesics, and opioids) for both human and veterinary use in the region were analyzed for the years 2016 to 2020, in relation to the inherent environmental hazard for each active pharmaceutical ingredient (API). We found that a total of 454 tons of analgesics were sold in the region during these 5 years. Classifications of environmental hazard were available for 16 out of the 45 studied APIs, accounting for 98.8% of the total mass in kilograms. Paracetamol, ibuprofen, and acetylsalicylic acid, which are all classified as low-hazard compounds, were the most commonly sold APIs. Diclofenac, the only pharmaceutical classified as high-hazard, was the fifth most commonly sold API, with a total sold mass of 2321 kg. The majority of the total sold mass of analgesics originated from dispensed prescriptions for human use in urban areas. Visualization of drug sales for humans and animals in different settings can be used to identify the environmental burden of pharmaceuticals. Based on our study, we suggest that additional measures to reduce the impacts of pharmaceuticals on the environment should primarily be directed to prescribing physicians in urban areas and campaigns targeted at the high over-the-counter sales of diclofenac. Moreover, it is important to address the fact that many pharmaceuticals currently have limited data on environmental hazard

System of Systems Simulation driven Urban Air Mobility Vehicle Design and Fleet Assessment

Urban Air Mobility (UAM) is increasingly becoming popular for Passenger or Cargo movement in dense smart cities. Several researches so far are focused on individual vehicle architectures such as multirotor or tiltrotor etc., but not much effort in a System of systems point of view where a homogenous fleet of vehicle with different passenger capacity, speed, and propulsive energy concepts are assessed in a framework for a successful UAM operations in a given city. An effort is made in this paper wherein, vehicle architecture is derived from the Concept of Operations (CONOPS) of scenarios such as urban and suburban operations and as well as propulsion subsystem for sustainable UAM. This paper approaches UAM aircraft design driven by System of Systems (SoS) approach and an agent-based simulation supports the vehicle architecture evaluation and fleet definition. The outcome of this study are: multiple aircraft design with subsystem architectures, ideal fleet size for the respective operational scenarios, autonomy and battery technology effectiveness on UAM throughput (to efficiently provide UAM on-demand service maximum passengers within 15 min wait time), and importantly, sustainability metrics such as total fleet energy required. Several System of Systems, system and subsystem level sensitivity research questions are addressed to understand the interlevel couplin

Prior Medications and the Cardiovascular Benefits From Combination Angiotensin‐Converting Enzyme Inhibition Plus Calcium Channel Blockade Among High‐Risk Hypertensive Patients

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142520/1/jah32856_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142520/2/jah32856.pd

Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Abstract: Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate

Seizure prediction : ready for a new era

Acknowledgements: The authors acknowledge colleagues in the international seizure prediction group for valuable discussions. L.K. acknowledges funding support from the National Health and Medical Research Council (APP1130468) and the James S. McDonnell Foundation (220020419) and acknowledges the contribution of Dean R. Freestone at the University of Melbourne, Australia, to the creation of Fig. 3.Peer reviewedPostprin

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation.

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis