Knowledge-based best of breed approach for automated detection of clinical events based on German free text digital hospital discharge letters

OBJECTIVES: The secondary use of medical data contained in electronic medical records, such as hospital discharge letters, is a valuable resource for the improvement of clinical care (e.g. in terms of medication safety) or for research purposes. However, the automated processing and analysis of medical free text still poses a huge challenge to available natural language processing (NLP) systems. The aim of this study was to implement a knowledge-based best of breed approach, combining a terminology server with integrated ontology, a NLP pipeline and a rules engine. METHODS: We tested the performance of this approach in a use case. The clinical event of interest was the particular drug-disease interaction "proton-pump inhibitor [PPI] use and osteoporosis". Cases were to be identified based on free text digital discharge letters as source of information. Automated detection was validated against a gold standard. RESULTS: Precision of recognition of osteoporosis was 94.19%, and recall was 97.45%. PPIs were detected with 100% precision and 97.97% recall. The F-score for the detection of the given drug-disease-interaction was 96,13%. CONCLUSION: We could show that our approach of combining a NLP pipeline, a terminology server, and a rules engine for the purpose of automated detection of clinical events such as drug-disease interactions from free text digital hospital discharge letters was effective. There is huge potential for the implementation in clinical and research contexts, as this approach enables analyses of very high numbers of medical free text documents within a short time period

Online-Informationssystem für die Phytotherapie bei Tieren

Die Phytotherapie gewinnt auch in der Veterinärmedizin zunehmend an Beliebtheit. Um das therapeutische Potenzial der Arzneipflanzen auszuschöpfen und deren sicheren Einsatz zu gewährleisten, bedarf es aber besonderer Kenntnisse der wirksamen Pflanzenteile beziehungsweise Zubereitungen. Unsachgemässe Anwendungen und Überdosierungen von Arzneipflanzen können toxisch sein. Deshalb haben wir mit www.phytoarznei.ch eine Entscheidungshilfe geschaffen, die online einen raschen Zugriff auf das aktuelle Wissen zu Arzneipflanzen und deren Gebrauch bei Tieren erlaubt. Dieses ­Informationssystem basiert auf der verfügbaren Fach­literatur, die nach kritischer Auswertung in eine strukturierte Datenbank eingebracht wurde. Für jede Arz­neipflanze beziehungsweise pflanzliche Droge sind therapeutische Indikationen, Anwendungsarten, organoleptische Eigenschaften, Inhaltsstoffe, pharmakologische Wirkungen, Dosierungen, Behandlungsdauer, Toxizität, gesetzliche Vorschriften bei Nutztieren sowie Dopingrelevanz aufgeführt. Zwei Suchprogramme gewährleisten einen benutzerfreundlichen Zugang, entweder durch die Eingabe des Pflanzennamens, des Drogennamens bzw. der Inhaltsstoffe der Pflanze in einem Suchfeld oder durch die Auswahl der gewünschten Tierspezies sowie therapeutischen Anwendung aus entsprechenden Dropdown-Listen. Diese Datenbank zu Arzneipflanzen ist mit der Giftpflanzendatenbank der Universität Zürich und, falls entsprechende Fertigpräparate vorliegen, mit dem Schweizerischen Tierarzneimittelkompendium sowie einem Verzeichnis von Veterinärprodukten verknüpft

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Loss of ATM kinase activity leads to embryonic lethality in mice

Ataxia telangiectasia (A-T) mutated (ATM) is a key deoxyribonucleic acid (DNA) damage signaling kinase that regulates DNA repair, cell cycle checkpoints, and apoptosis. The majority of patients with A-T, a cancer-prone neurodegenerative disease, present with null mutations in Atm. To determine whether the functions of ATM are mediated solely by its kinase activity, we generated two mouse models containing single, catalytically inactivating point mutations in Atm. In this paper, we show that, in contrast to Atm-null mice, both D2899A and Q2740P mutations cause early embryonic lethality in mice, without displaying dominant-negative interfering activity. Using conditional deletion, we find that the D2899A mutation in adult mice behaves largely similar to Atm-null cells but shows greater deficiency in homologous recombination (HR) as measured by hypersensitivity to poly (adenosine diphosphate-ribose) polymerase inhibition and increased genomic instability. These results may explain why missense mutations with no detectable kinase activity are rarely found in patients with classical A-T. We propose that ATM kinase-inactive missense mutations, unless otherwise compensated for, interfere with HR during embryogenesis

Contactless microwave sensors and their application in biological single use

In bioprocess technology, highly-sensitive robust sensors are required for operation in single use bioreactors (SUB) without direct contact to the fluid under analysis. Measuring the change of dielectric properties (permittivity and conductivity) at microwave frequencies allows the investigation of biological and chemical matter and processes, e.g., cell growth, cell metabolism and the concentration of large aqueous based molecules. This contribution describes a high frequency sensor that combines detection in macro- or microfluidic networks with quick and precise analysis. These kinds of sensors can be installed directly to the outer surface of the culture device (Figure 1) or can be clamped onto tubing (Figure 2). A clamped on sensor consists of a fluidic channel placed between a micro-strip line waveguide combined with resonant properties. Please click Additional Files below to see the full abstract

Arkeologiske og naturvitenskapelige undersøkelser av hus, bosetningsspor, branngrav og dyrkingslag fra senneolitikum til middelalder ved Harestadkrysset, Randaberg k. (Id 177645: gnr. 49 /bnr 12, 16 & Id 177662: gnr. 48 / bnr 1112, 1113)

Oppdragsgiver: Statens vegvesenRapporten omhandler den arkeologiske og naturvitenskapelige undersøkelsen av lokalitetene Id 177645 & Id 177662 i regi av Arkeologisk museum, UiS. Lokalitetene ligger helt nord på Jæren i Randaberg kommune, Rogaland i fulldyrket jordbrukslandskap ved kysten. Lokalitet Id 177645 ligger på gården Harestad, gnr. 49/ bnr 12 & 16, mens lokalitet Id 177662 ligger på gården Grødem, bnr. 48 / bnr. 1112 & 1113. Utgravningene ble gjennomført på to sesonger, i 2021 ble det gravd i felt fra 13. april – 03. september og i 2022 foregikk utgravingen fra 20.april – 02. september. På lokaliteten Id 177645 ble diverse bosetnings- og aktivitetsspor undersøkt, mens på lokalitet Id 177662 var det registrert dyrkingslag. Bakgrunnen for undersøkelsen er veibygging i forbindelse med Rogfast-prosjektet om fergefri E 39. Reguleringsplanen ble vedtatt 10. september 2015 og den 26. januar fattet Riksantikvaren vedtak om utgifter til særskilt gransking av automatisk fredet kulturminner etter kulturminneloven § 10 første ledd. Tiltakshaver var statens veivesen som dekker utgiftene for undersøkelsen i samsvar med kulturminneloven § 8 fjerde ledd. Utgravingen avdekket en rekke varierte bosetnings- og aktivitetsspor fra yngre steinalder til tidlig middelalder. Ved arkeo-botaniske undersøkelser ble det påvist omfattende spor etter forhistorisk dyrking av forskjellige vekster fra alle perioder. Mange arkeologiske strukturer var sterkt forstyrret av moderne jordbruk, men enkelte anlegg pekte seg positivt ut. Flere hus fra førromersk jernalder ble dokumentert, ved siden av et bolighus, er særlig en bygning bemerkelsesverdig som sannsynligvis ble brukt til å tørke og oppbevare jordbruksprodukter. En annen tyngdepunkt av de arkeologiske resultatene skulle vise seg å være forholdsvis omfattende spor fra merovingertiden, altså yngre jernalder. Flere hus kunne dokumenteres og dateres til denne perioden, hvor det åpenbart ble dyrket belgfrukter, som hittil ikke var kjent fra denne tiden. I tillegg ble det også undersøkt en branngrav fra merovingertiden, som også er en ellers lite kjent funngruppe i Rogaland. Utgravingene på lokalitet Id 177645 ved Harestad har dermed gitt viktige informasjoner om langtidsutviklingen av bosetningen og jordbruket på Nord-Jæren. Særlig fra merovingertid er det ikke kjent mange funnsteder, funnene fra undersøkelsen kan derfor gi nye verdifulle innfallsvinkler til fremtidig forskning

Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan

Dipeptidyl-Peptidase Activity of Meprin β Links N-truncation of Aβ with Glutaminyl Cyclase-Catalyzed pGlu-Aβ Formation

The formation of amyloid-β (Aβ) peptides is causally involved in the development of Alzheimer’s disease (AD). A significant proportion of deposited Aβ is N-terminally truncated and modified at the N-terminus by a pGlu-residue (pGlu-Aβ). These forms show enhanced neurotoxicity compared to full-length Aβ. Although the truncation may occur by aminopeptidases after formation of Aβ, recently discovered processing pathways of amyloid-β protein precursor (AβPP) by proteases such as meprin β may also be involved. Here, we assessed a role of meprin β in forming Aβ3 -40/42 , which is the precursor of pGlu-Aβ3 -40/42 generated by glutaminyl cyclase (QC). Similar to QC, meprin β mRNA is significantly upregulated in postmortem brain from AD patients. A histochemical analysis supports the presence of meprin β in neurons and astrocytes in the vicinity of pGlu-Aβ containing deposits. Cleavage of AβPP-derived peptides by meprin β in vitro results in peptides Aβ1 -x , Aβ2 -x , and Aβ3 -x . The formation of N-truncated Aβ by meprin β was also corroborated in cell culture. A subset of the generated peptides was converted into pGlu-Aβ3 -40 by an addition of glutaminyl cyclase, supporting the preceding formation of Aβ3 -40 . Further analysis of the meprin β cleavage revealed a yet unknown dipeptidyl-peptidase–like activity specific for the N-terminus of Aβ1 -x . Thus, our data suggest that meprin β contributes to the formation of N-truncated Aβ by endopeptidase and exopeptidase activity to generate the substrate for QC-catalyzed pGlu-Aβ formation

Differences in biocompatibility of microneedles from cyclic olefin polymers with human endothelial and epithelial skin cells

Microneedles are promising devices for transdermal delivery and diagnostic applications, due to their minimally invasive and painless nature of application. However, so far, applications are limited to small scale research projects. Material selection and production for larger projects remain a challenge. In vitro testing using human cell culture could bridge the gap between cost effective screening of suitable materials and concerns for safety and ethics. In this study, materials were tested for effects on viability and morphology of human endothelial cells and keratinocytes. In addition, materials were assessed for their potential to influence cellular differentiation and barrier formation. Elution-based testing of inflammatory markers revealed no negative effects in all applied tests, whereas the assessment of differentiation markers on cells in direct contact with the material showed differences and allowed the selection of candidate materials for future medical device applications. This study illustrates that elution-based biocompatibility testing can paint an incomplete picture. Advanced staining techniques and cell types specific for the application of the medical device improve material selection to reduce and replace animal testing at an early stage in the development process. © 2018 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 505–512, 2019

Формирование эмоциональной культуры как компонента инновационной культуры студентов

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been