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

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

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

AJAM-A–tetraspanin–αvβ5 integrin complex regulates contact inhibition of locomotion

Contact inhibition of locomotion (CIL) is a process that regulates cell motility upon collision with other cells. Improper regulation of CIL has been implicated in cancer cell dissemination. Here, we identify the cell adhesion molecule JAM-A as a central regulator of CIL in tumor cells. JAM-A is part of a multimolecular signaling complex in which tetraspanins CD9 and CD81 link JAM-A to αvβ5 integrin. JAM-A binds Csk and inhibits the activity of αvβ5 integrin-associated Src. Loss of JAM-A results in increased activities of downstream effectors of Src, including Erk1/2, Abi1, and paxillin, as well as increased activity of Rac1 at cell–cell contact sites. As a consequence, JAM-A-depleted cells show increased motility, have a higher cell–matrix turnover, and fail to halt migration when colliding with other cells. We also find that proper regulation of CIL depends on αvβ5 integrin engagement. Our findings identify a molecular mechanism that regulates CIL in tumor cells and have implications on tumor cell dissemination.publishedVersio

AntibioticScout.ch: Entscheidungshilfe für den umsichtigen Einsatz von antimikrobiellen Wirkstoffen: Anwendung beim Rind

The administration of antibiotics in livestock has been criticized for many years, in particular because of an inappropriate use and the appearance of antibiotic residues in the environment, which can promote the emergence and spread of resistant bacteria. However, antibiotics are essential for the successful and sustainable control of bacterial pathogens. With the aim of optimizing the use of antibiotics in food animals and minimizing the prevalence of resistant bacteria, AntibioticScout. ch provides a decision aid for the prudent use of antimicrobial drugs. This approach emphasizes the importance of supportive therapy and the hallmarks of preventive concepts. Procedures to improve animal health and animal welfare in accordance with the principles of good veterinary practice are primary and effective tools to reduce the use of antimicrobial drugs. The necessary reduction in the use of antibiotics must, therefore, be accompanied by appropriate management strategies in animal husbandry. In particular, hygiene, animal welfare and biosecurity measures are crucial to ensure an optimal health status in farm animals

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

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

Is healthy neuroticism associated with longevity? A coordinated integrative data analysis

Early investigations of the neuroticism by conscientiousness interaction with regards to health have been promising, but to date, there have been no systematic investigations of this interaction that account for the various personality measurement instruments, varying populations, or aspects of health. The current study - the second of three - uses a coordinated analysis approach to test the impact of the neuroticism by conscientiousness interaction on the prevalence and incidence of chronic conditions. Using 15 pre-existing longitudinal studies (N > 49,375), we found that conscientiousness did not moderate the relationship between neuroticism and having hypertension (OR = 1.00,95%CI[0.98,1.02]), diabetes (OR = 1.02[0.99,1.04]), or heart disease (OR = 0.99[0.97,1.01]). Similarly, we found that conscientiousness did not moderate the prospective relationship between neuroticism and onset of hypertension (OR = 0.98,[0.95,1.01]), diabetes (OR = 0.99[0.94,1.05]), or heart disease (OR = 0.98[0.94,1.03]). Heterogeneity of effect sizes was largely nonsignificant, with one exception, indicating that the effects are consistent between datasets. Overall, we conclude that there is no evidence that healthy neuroticism, operationalized as the conscientiousness by neuroticism interaction, buffers against chronic conditions

Cannabinoid modulation of limbic forebrain noradrenergic circuitry

Both the endocannabinoid and noradrenergic systems have been implicated in neuropsychiatric disorders. Importantly, low levels of norepinephrine are seen in patients with depression, and antagonism of the cannabinoid receptor type 1 (CB1R) is able to induce depressive symptoms in rodents and humans. Whether the interaction between the two systems is important for the regulation of these behaviors is not known. In the present study, adult male Sprague-Dawley rats were acutely or chronically administered the CB1R synthetic agonist WIN 55,212-2, and alpha2A and beta1 adrenergic receptors (AR) were quantified by Western blot. These AR have been shown to be altered in a number of psychiatric disorders and following antidepressant treatment. CB1R agonist treatment induced a differential decrease in alpha2A- and beta1-ARs in the nucleus accumbens (Acb). Moreover, to assess long-lasting changes induced by CB1R activation, some of the chronically treated rats were killed 7 days following the last injection. This revealed a persistent effect on alpha2A-AR levels. Furthermore, the localization of CB1R with respect to noradrenergic profiles was assessed in the Acb and in the nucleus of the solitary tract (NTS). Our results show a significant topographic distribution of CB1R and dopamine beta hydroxylase immunoreactivities (ir) in the Acb, with higher co-localization observed in the NTS. In the Acb, CB1R-ir was found in terminals forming either symmetric or asymmetric synapses. These results suggest that cannabinoids may modulate noradrenergic signaling in the Acb, directly by acting on noradrenergic neurons in the NTS or indirectly by modulating inhibitory and excitatory input in the Acb.This works was supported by PHS grant DA 020129. A.F.C. was supported by the Portuguese Foundation for Science and Technology (SFRH/BD/33236/2007)