TY - JOUR A1 - Lewkowicz, Daniel A1 - Wohlbrandt, Attila A1 - Böttinger, Erwin T1 - Economic impact of clinical decision support interventions based on electronic health records JF - BMC Health Services Research N2 - Background Unnecessary healthcare utilization, non-adherence to current clinical guidelines, or insufficient personalized care are perpetual challenges and remain potential major cost-drivers for healthcare systems around the world. Implementing decision support systems into clinical care is promised to improve quality of care and thereby yield substantial effects on reducing healthcare expenditure. In this article, we evaluate the economic impact of clinical decision support (CDS) interventions based on electronic health records (EHR). Methods We searched for studies published after 2014 using MEDLINE, CENTRAL, WEB OF SCIENCE, EBSCO, and TUFTS CEA registry databases that encompass an economic evaluation or consider cost outcome measures of EHR based CDS interventions. Thereupon, we identified best practice application areas and categorized the investigated interventions according to an existing taxonomy of front-end CDS tools. Results and discussion Twenty-seven studies are investigated in this review. Of those, twenty-two studies indicate a reduction of healthcare expenditure after implementing an EHR based CDS system, especially towards prevalent application areas, such as unnecessary laboratory testing, duplicate order entry, efficient transfusion practice, or reduction of antibiotic prescriptions. On the contrary, order facilitators and undiscovered malfunctions revealed to be threats and could lead to new cost drivers in healthcare. While high upfront and maintenance costs of CDS systems are a worldwide implementation barrier, most studies do not consider implementation cost. Finally, four included economic evaluation studies report mixed monetary outcome results and thus highlight the importance of further high-quality economic evaluations for these CDS systems. Conclusion Current research studies lack consideration of comparative cost-outcome metrics as well as detailed cost components in their analyses. Nonetheless, the positive economic impact of EHR based CDS interventions is highly promising, especially with regard to reducing waste in healthcare. KW - Economic evaluation KW - Electronic health record KW - Clinical decision support KW - Behavioral economics Y1 - 2020 U6 - https://doi.org/10.1186/s12913-020-05688-3 SN - 1472-6963 VL - 20 PB - BioMed Central CY - London ER - TY - JOUR A1 - Wachs, Sebastian A1 - Wettstein, Alexander A1 - Bilz, Ludwig A1 - Gamez-Guadix, Manuel T1 - Motivos del discurso de odio en la adolescencia y su relación con las normas sociales BT - Adolescents' motivations to perpetrate hate speech and links with social norms JF - Comunicar : revista científica de comunicación y educación N2 - Hate speech has become a widespread phenomenon, however, it remains largely unclear why adolescents engage in it and which factors are associated with their motivations for perpetrating hate speech. To this end, we developed the multidimensional "Motivations for Hate Speech Perpetration Scale" (MHATE) and evaluated the psychometric properties. We also explored the associations between social norms and adolescents' motivations for hate speech perpetration. The sample consisted of 346 adolescents from Switzerland (54.6% boys; Mage=14; SD=0.96) who reported engagement in hate speech as perpetrators. The analyses revealed good psychometric properties for the MHATE, including good internal consistency. The most frequently endorsed subscale was revenge, followed by ideology, group conformity, status enhancement, exhilaration, and power. The results also showed that descriptive norms and peer pressure were related to a wide range of different motivations for perpetrating hate speech. Injunctive norms, however, were only associated with power. In conclusion, findings indicate that hate speech fulfills various functions. We argue that knowing the specific motivations that underlie hate speech could help us derive individually tailored prevention strategies (e.g., anger management, promoting an inclusive classroom climate). Furthermore, we suggest that practitioners working in the field of hate speech prevention give special attention to social norms surrounding adolescents. KW - Hate speech KW - cyberhate KW - motives KW - social norms KW - injunctive norms KW - peer KW - pressure Y1 - 2022 U6 - https://doi.org/10.3916/C71-2022-01 SN - 1134-3478 SN - 1988-3293 VL - 30 IS - 71 SP - 9 EP - 20 PB - Grupo Comunicar CY - Huelva ER - TY - JOUR A1 - Smith, Taylor A1 - Boers, Niklas T1 - Global vegetation resilience linked to water availability and variability JF - Nature Communications N2 - Quantifying the resilience of vegetated ecosystems is key to constraining both present-day and future global impacts of anthropogenic climate change. Here we apply both empirical and theoretical resilience metrics to remotely-sensed vegetation data in order to examine the role of water availability and variability in controlling vegetation resilience at the global scale. We find a concise global relationship where vegetation resilience is greater in regions with higher water availability. We also reveal that resilience is lower in regions with more pronounced inter-annual precipitation variability, but find less concise relationships between vegetation resilience and intra-annual precipitation variability. Our results thus imply that the resilience of vegetation responds differently to water deficits at varying time scales. In view of projected increases in precipitation variability, our findings highlight the risk of ecosystem degradation under ongoing climate change. Vegetation dynamics depend on both the amount of precipitation and its variability over time. Here, the authors show that vegetation resilience is greater where water availability is higher and where precipitation is more stable from year to year. Y1 - 2023 U6 - https://doi.org/10.1038/s41467-023-36207-7 SN - 2041-1723 VL - 14 IS - 1 PB - Springer Nature CY - London ER - TY - JOUR A1 - Falkenhagen, Undine A1 - Knöchel, Jane A1 - Kloft, Charlotte A1 - Huisinga, Wilhelm T1 - Deriving mechanism-based pharmacodynamic models by reducing quantitative systems pharmacology models BT - an application to warfarin JF - CPT: Pharmacometrics & Systems Pharmacology N2 - Quantitative systems pharmacology (QSP) models integrate comprehensive qualitative and quantitative knowledge about pharmacologically relevant processes. We previously proposed a first approach to leverage the knowledge in QSP models to derive simpler, mechanism-based pharmacodynamic (PD) models. Their complexity, however, is typically still too large to be used in the population analysis of clinical data. Here, we extend the approach beyond state reduction to also include the simplification of reaction rates, elimination of reactions, and analytic solutions. We additionally ensure that the reduced model maintains a prespecified approximation quality not only for a reference individual but also for a diverse virtual population. We illustrate the extended approach for the warfarin effect on blood coagulation. Using the model-reduction approach, we derive a novel small-scale warfarin/international normalized ratio model and demonstrate its suitability for biomarker identification. Due to the systematic nature of the approach in comparison with empirical model building, the proposed model-reduction algorithm provides an improved rationale to build PD models also from QSP models in other applications. Y1 - 2023 U6 - https://doi.org/10.1002/psp4.12903 SN - 2163-8306 VL - 12 IS - 4 SP - 432 EP - 443 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Datta, Suparno A1 - Sachs, Jan Philipp A1 - Freitas da Cruz, Harry A1 - Martensen, Tom A1 - Bode, Philipp A1 - Morassi Sasso, Ariane A1 - Glicksberg, Benjamin S. A1 - Böttinger, Erwin T1 - FIBER BT - enabling flexible retrieval of electronic health records data for clinical predictive modeling JF - JAMIA open N2 - Objectives: The development of clinical predictive models hinges upon the availability of comprehensive clinical data. Tapping into such resources requires considerable effort from clinicians, data scientists, and engineers. Specifically, these efforts are focused on data extraction and preprocessing steps required prior to modeling, including complex database queries. A handful of software libraries exist that can reduce this complexity by building upon data standards. However, a gap remains concerning electronic health records (EHRs) stored in star schema clinical data warehouses, an approach often adopted in practice. In this article, we introduce the FlexIBle EHR Retrieval (FIBER) tool: a Python library built on top of a star schema (i2b2) clinical data warehouse that enables flexible generation of modeling-ready cohorts as data frames. Materials and Methods: FIBER was developed on top of a large-scale star schema EHR database which contains data from 8 million patients and over 120 million encounters. To illustrate FIBER's capabilities, we present its application by building a heart surgery patient cohort with subsequent prediction of acute kidney injury (AKI) with various machine learning models. Results: Using FIBER, we were able to build the heart surgery cohort (n = 12 061), identify the patients that developed AKI (n = 1005), and automatically extract relevant features (n = 774). Finally, we trained machine learning models that achieved area under the curve values of up to 0.77 for this exemplary use case. Conclusion: FIBER is an open-source Python library developed for extracting information from star schema clinical data warehouses and reduces time-to-modeling, helping to streamline the clinical modeling process. KW - databases KW - factual KW - electronic health records KW - information storage and KW - retrieval KW - workflow KW - software/instrumentation Y1 - 2021 U6 - https://doi.org/10.1093/jamiaopen/ooab048 SN - 2574-2531 VL - 4 IS - 3 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Cope, Justin L. A1 - Baukmann, Hannes A. A1 - Klinger, Jörn E. A1 - Ravarani, Charles N. J. A1 - Böttinger, Erwin A1 - Konigorski, Stefan A1 - Schmidt, Marco F. T1 - Interaction-based feature selection algorithm outperforms polygenic risk score in predicting Parkinson’s Disease status JF - Frontiers in genetics N2 - Polygenic risk scores (PRS) aggregating results from genome-wide association studies are the state of the art in the prediction of susceptibility to complex traits or diseases, yet their predictive performance is limited for various reasons, not least of which is their failure to incorporate the effects of gene-gene interactions. Novel machine learning algorithms that use large amounts of data promise to find gene-gene interactions in order to build models with better predictive performance than PRS. Here, we present a data preprocessing step by using data-mining of contextual information to reduce the number of features, enabling machine learning algorithms to identify gene-gene interactions. We applied our approach to the Parkinson's Progression Markers Initiative (PPMI) dataset, an observational clinical study of 471 genotyped subjects (368 cases and 152 controls). With an AUC of 0.85 (95% CI = [0.72; 0.96]), the interaction-based prediction model outperforms the PRS (AUC of 0.58 (95% CI = [0.42; 0.81])). Furthermore, feature importance analysis of the model provided insights into the mechanism of Parkinson's disease. For instance, the model revealed an interaction of previously described drug target candidate genes TMEM175 and GAPDHP25. These results demonstrate that interaction-based machine learning models can improve genetic prediction models and might provide an answer to the missing heritability problem. KW - epistasis KW - machine learning KW - feature selection KW - parkinson's disease KW - PPMI (parkinson's progression markers initiative) Y1 - 2021 U6 - https://doi.org/10.3389/fgene.2021.744557 SN - 1664-8021 VL - 12 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Zenner, Alexander M. A1 - Böttinger, Erwin A1 - Konigorski, Stefan T1 - StudyMe BT - a new mobile app for user-centric N-of-1 trials JF - Trials N2 - N-of-1 trials are multi-crossover self-experiments that allow individuals to systematically evaluate the effect of interventions on their personal health goals. Although several tools for N-of-1 trials exist, there is a gap in supporting non-experts in conducting their own user-centric trials. In this study, we present StudyMe, an open-source mobile application that is freely available from https://play.google.com/store/apps/details?id=health.studyu.me and offers users flexibility and guidance in configuring every component of their trials. We also present research that informed the development of StudyMe, focusing on trial creation. Through an initial survey with 272 participants, we learned that individuals are interested in a variety of personal health aspects and have unique ideas on how to improve them. In an iterative, user-centered development process with intermediate user tests, we developed StudyMe that features an educational part to communicate N-of-1 trial concepts. A final empirical evaluation of StudyMe showed that all participants were able to create their own trials successfully using StudyMe and the app achieved a very good usability rating. Our findings suggest that StudyMe provides a significant step towards enabling individuals to apply a systematic science-oriented approach to personalize health-related interventions and behavior modifications in their everyday lives. Y1 - 2022 U6 - https://doi.org/10.1186/s13063-022-06893-7 SN - 1745-6215 VL - 23 PB - BioMed Central CY - London ER - TY - JOUR A1 - Lewkowicz, Daniel A1 - Böttinger, Erwin A1 - Siegel, Martin T1 - Economic evaluation of digital therapeutic care apps for unsupervised treatment of low back pain BT - Monte Carlo Simulation JF - JMIR mhealth and uhealth N2 - Background: Digital therapeutic care (DTC) programs are unsupervised app-based treatments that provide video exercises and educational material to patients with nonspecific low back pain during episodes of pain and functional disability. German statutory health insurance can reimburse DTC programs since 2019, but evidence on efficacy and reasonable pricing remains scarce. This paper presents a probabilistic sensitivity analysis (PSA) to evaluate the efficacy and cost-utility of a DTC app against treatment as usual (TAU) in Germany. Objective: The aim of this study was to perform a PSA in the form of a Monte Carlo simulation based on the deterministic base case analysis to account for model assumptions and parameter uncertainty. We also intend to explore to what extent the results in this probabilistic analysis differ from the results in the base case analysis and to what extent a shortage of outcome data concerning quality-of-life (QoL) metrics impacts the overall results. Methods: The PSA builds upon a state-transition Markov chain with a 4-week cycle length over a model time horizon of 3 years from a recently published deterministic cost-utility analysis. A Monte Carlo simulation with 10,000 iterations and a cohort size of 10,000 was employed to evaluate the cost-utility from a societal perspective. Quality-adjusted life years (QALYs) were derived from Veterans RAND 6-Dimension (VR-6D) and Short-Form 6-Dimension (SF-6D) single utility scores. Finally, we also simulated reducing the price for a 3-month app prescription to analyze at which price threshold DTC would result in being the dominant strategy over TAU in Germany. Results: The Monte Carlo simulation yielded on average a euro135.97 (a currency exchange rate of EUR euro1=US $1.069 is applicable) incremental cost and 0.004 incremental QALYs per person and year for the unsupervised DTC app strategy compared to in-person physiotherapy in Germany. The corresponding incremental cost-utility ratio (ICUR) amounts to an additional euro34,315.19 per additional QALY. DTC yielded more QALYs in 54.96% of the iterations. DTC dominates TAU in 24.04% of the iterations for QALYs. Reducing the app price in the simulation from currently euro239.96 to euro164.61 for a 3-month prescription could yield a negative ICUR and thus make DTC the dominant strategy, even though the estimated probability of DTC being more effective than TAU is only 54.96%. Conclusions: Decision-makers should be cautious when considering the reimbursement of DTC apps since no significant treatment effect was found, and the probability of cost-effectiveness remains below 60% even for an infinite willingness-to-pay threshold. More app-based studies involving the utilization of QoL outcome parameters are urgently needed to account for the low and limited precision of the available QoL input parameters, which are crucial to making profound recommendations concerning the cost-utility of novel apps. KW - cost-utility analysis KW - cost KW - probabilistic sensitivity analysis KW - Monte Carlo simulation KW - low back pain KW - pain KW - economic KW - cost-effectiveness KW - Markov model KW - digital therapy KW - digital health app KW - mHealth KW - mobile health KW - health app KW - mobile app KW - orthopedic KW - QUALY KW - DALY KW - quality-adjusted life years KW - disability-adjusted life years KW - time horizon KW - veteran KW - statistics Y1 - 2023 U6 - https://doi.org/10.2196/44585 SN - 2291-5222 VL - 11 PB - JMIR Publications CY - Toronto ER - TY - JOUR A1 - Konigorski, Stefan A1 - Wernicke, Sarah A1 - Slosarek, Tamara A1 - Zenner, Alexander M. A1 - Strelow, Nils A1 - Ruether, Darius F. A1 - Henschel, Florian A1 - Manaswini, Manisha A1 - Pottbäcker, Fabian A1 - Edelman, Jonathan A. A1 - Owoyele, Babajide A1 - Danieletto, Matteo A1 - Golden, Eddye A1 - Zweig, Micol A1 - Nadkarni, Girish N. A1 - Böttinger, Erwin T1 - StudyU: a platform for designing and conducting innovative digital N-of-1 trials JF - Journal of medical internet research N2 - N-of-1 trials are the gold standard study design to evaluate individual treatment effects and derive personalized treatment strategies. Digital tools have the potential to initiate a new era of N-of-1 trials in terms of scale and scope, but fully functional platforms are not yet available. Here, we present the open source StudyU platform, which includes the StudyU Designer and StudyU app. With the StudyU Designer, scientists are given a collaborative web application to digitally specify, publish, and conduct N-of-1 trials. The StudyU app is a smartphone app with innovative user-centric elements for participants to partake in trials published through the StudyU Designer to assess the effects of different interventions on their health. Thereby, the StudyU platform allows clinicians and researchers worldwide to easily design and conduct digital N-of-1 trials in a safe manner. We envision that StudyU can change the landscape of personalized treatments both for patients and healthy individuals, democratize and personalize evidence generation for self-optimization and medicine, and can be integrated in clinical practice. KW - digital interventions KW - N-of-1 trial KW - SCED KW - single-case experimental design KW - web application KW - mobile application KW - app KW - digital health Y1 - 2022 U6 - https://doi.org/10.2196/35884 SN - 1439-4456 SN - 1438-8871 VL - 24 IS - 7 PB - Healthcare World CY - Richmond, Va. ER - TY - JOUR A1 - Barbolini, Natasha A1 - Woutersen, Amber A1 - Dupont-Nivet, Guillaume A1 - Silvestro, Daniele A1 - Tardif-Becquet, Delphine A1 - Coster, Pauline M. C. A1 - Meijer, Niels A1 - Chang, Cun A1 - Zhang, Hou-Xi A1 - Licht, Alexis A1 - Rydin, Catarina A1 - Koutsodendris, Andreas A1 - Han, Fang A1 - Rohrmann, Alexander A1 - Liu, Xiang-Jun A1 - Zhang, Y. A1 - Donnadieu, Yannick A1 - Fluteau, Frederic A1 - Ladant, Jean-Baptiste A1 - Le Hir, Guillaume A1 - Hoorn, M. Carina T1 - Cenozoic evolution of the steppe-desert biome in Central Asia JF - Science Advances N2 - The origins and development of the arid and highly seasonal steppe-desert biome in Central Asia, the largest of its kind in the world, remain largely unconstrained by existing records. It is unclear how Cenozoic climatic, geological, and biological forces, acting at diverse spatial and temporal scales, shaped Central Asian ecosystems through time. Our synthesis shows that the Central Asian steppe-desert has existed since at least Eocene times but experienced no less than two regime shifts, one at the Eocene-Oligocene Transition and one in the mid-Miocene. These shifts separated three successive "stable states," each characterized by unique floral and faunal structures. Past responses to disturbance in the Asian steppe-desert imply that modern ecosystems are unlikely to recover their present structures and diversity if forced into a new regime. This is of concern for Asian steppes today, which are being modified for human use and lost to desertification at unprecedented rates. Y1 - 2020 U6 - https://doi.org/10.1126/sciadv.abb8227 SN - 2375-2548 VL - 6 IS - 41 PB - American Association for the Advancement of Science CY - Washington ER - TY - JOUR A1 - Woutersen, Amber A1 - Jardine, Phillip E. A1 - Giovanni Bogota-Angel, Raul A1 - Zhang, Hong-Xiang A1 - Silvestro, Daniele A1 - Antonelli, Alexandre A1 - Gogna, Elena A1 - Erkens, Roy H. J. A1 - Gosling, William D. A1 - Dupont-Nivet, Guillaume A1 - Hoorn, Carina T1 - A novel approach to study the morphology and chemistry of pollen in a phylogenetic context, applied to the halophytic taxon Nitraria L.(Nitrariaceae) JF - PeerJ N2 - Nitraria is a halophytic taxon (i.e., adapted to saline environments) that belongs to the plant family Nitrariaceae and is distributed from the Mediterranean, across Asia into the south-eastern tip of Australia. This taxon is thought to have originated in Asia during the Paleogene (66-23 Ma), alongside the proto-Paratethys epicontinental sea. The evolutionary history of Nitraria might hold important clues on the links between climatic and biotic evolution but limited taxonomic documentation of this taxon has thus far hindered this line of research. Here we investigate if the pollen morphology and the chemical composition of the pollen wall are informative of the evolutionary history of Nitraria and could explain if origination along the proto-Paratethys and dispersal to the Tibetan Plateau was simultaneous or a secondary process. To answer these questions, we applied a novel approach consisting of a combination of Fourier Transform Infrared spectroscopy (FTIR), to determine the chemical composition of the pollen wall, and pollen morphological analyses using Light Microscopy (LM) and Scanning Electron Microscopy (SEM). We analysed our data using ordinations (principal components analysis and non-metric multidimensional scaling), and directly mapped it on the Nitrariaceae phylogeny to produce a phylomorphospace and a phylochemospace. Our LM, SEM and FTIR analyses show clear morphological and chemical differences between the sister groups Peganum and Nitraria. Differences in the morphological and chemical characteristics of highland species (Nitraria schoberi, N. sphaerocarpa, N. sibirica and N. tangutorum) and lowland species (Nitraria billardierei and N. retusa) are very subtle, with phylogenetic history appearing to be a more important control on Nitraria pollen than local environmental conditions. Our approach shows a compelling consistency between the chemical and morphological characteristics of the eight studied Nitrariaceae species, and these traits are in agreement with the phylogenetic tree. Taken together, this demonstrates how novel methods for studying fossil pollen can facilitate the evolutionary investigation of living and extinct taxa, and the environments they represent. KW - FTIR KW - LM KW - SEM KW - Paratethys KW - Tibet KW - Sporopollenin KW - Mediterranean KW - Steppe-desert KW - Australia KW - Palynology Y1 - 2018 U6 - https://doi.org/10.7717/peerj.5055 SN - 2167-8359 VL - 6 PB - PeerJ Inc. CY - London ER - TY - JOUR A1 - Vaid, Akhil A1 - Somani, Sulaiman A1 - Russak, Adam J. A1 - De Freitas, Jessica K. A1 - Chaudhry, Fayzan F. A1 - Paranjpe, Ishan A1 - Johnson, Kipp W. A1 - Lee, Samuel J. A1 - Miotto, Riccardo A1 - Richter, Felix A1 - Zhao, Shan A1 - Beckmann, Noam D. A1 - Naik, Nidhi A1 - Kia, Arash A1 - Timsina, Prem A1 - Lala, Anuradha A1 - Paranjpe, Manish A1 - Golden, Eddye A1 - Danieletto, Matteo A1 - Singh, Manbir A1 - Meyer, Dara A1 - O'Reilly, Paul F. A1 - Huckins, Laura A1 - Kovatch, Patricia A1 - Finkelstein, Joseph A1 - Freeman, Robert M. A1 - Argulian, Edgar A1 - Kasarskis, Andrew A1 - Percha, Bethany A1 - Aberg, Judith A. A1 - Bagiella, Emilia A1 - Horowitz, Carol R. A1 - Murphy, Barbara A1 - Nestler, Eric J. A1 - Schadt, Eric E. A1 - Cho, Judy H. A1 - Cordon-Cardo, Carlos A1 - Fuster, Valentin A1 - Charney, Dennis S. A1 - Reich, David L. A1 - Böttinger, Erwin A1 - Levin, Matthew A. A1 - Narula, Jagat A1 - Fayad, Zahi A. A1 - Just, Allan C. A1 - Charney, Alexander W. A1 - Nadkarni, Girish N. A1 - Glicksberg, Benjamin S. T1 - Machine learning to predict mortality and critical events in a cohort of patients with COVID-19 in New York City: model development and validation JF - Journal of medical internet research : international scientific journal for medical research, information and communication on the internet ; JMIR N2 - Background: COVID-19 has infected millions of people worldwide and is responsible for several hundred thousand fatalities. The COVID-19 pandemic has necessitated thoughtful resource allocation and early identification of high-risk patients. However, effective methods to meet these needs are lacking. Objective: The aims of this study were to analyze the electronic health records (EHRs) of patients who tested positive for COVID-19 and were admitted to hospitals in the Mount Sinai Health System in New York City; to develop machine learning models for making predictions about the hospital course of the patients over clinically meaningful time horizons based on patient characteristics at admission; and to assess the performance of these models at multiple hospitals and time points. Methods: We used Extreme Gradient Boosting (XGBoost) and baseline comparator models to predict in-hospital mortality and critical events at time windows of 3, 5, 7, and 10 days from admission. Our study population included harmonized EHR data from five hospitals in New York City for 4098 COVID-19-positive patients admitted from March 15 to May 22, 2020. The models were first trained on patients from a single hospital (n=1514) before or on May 1, externally validated on patients from four other hospitals (n=2201) before or on May 1, and prospectively validated on all patients after May 1 (n=383). Finally, we established model interpretability to identify and rank variables that drive model predictions. Results: Upon cross-validation, the XGBoost classifier outperformed baseline models, with an area under the receiver operating characteristic curve (AUC-ROC) for mortality of 0.89 at 3 days, 0.85 at 5 and 7 days, and 0.84 at 10 days. XGBoost also performed well for critical event prediction, with an AUC-ROC of 0.80 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. In external validation, XGBoost achieved an AUC-ROC of 0.88 at 3 days, 0.86 at 5 days, 0.86 at 7 days, and 0.84 at 10 days for mortality prediction. Similarly, the unimputed XGBoost model achieved an AUC-ROC of 0.78 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. Trends in performance on prospective validation sets were similar. At 7 days, acute kidney injury on admission, elevated LDH, tachypnea, and hyperglycemia were the strongest drivers of critical event prediction, while higher age, anion gap, and C-reactive protein were the strongest drivers of mortality prediction. Conclusions: We externally and prospectively trained and validated machine learning models for mortality and critical events for patients with COVID-19 at different time horizons. These models identified at-risk patients and uncovered underlying relationships that predicted outcomes. KW - machine learning KW - COVID-19 KW - electronic health record KW - TRIPOD KW - clinical KW - informatics KW - prediction KW - mortality KW - EHR KW - cohort KW - hospital KW - performance Y1 - 2020 U6 - https://doi.org/10.2196/24018 SN - 1439-4456 SN - 1438-8871 VL - 22 IS - 11 PB - Healthcare World CY - Richmond, Va. ER - TY - JOUR A1 - Döll, Stefanie A1 - Djalali Farahani-Kofoet, Roxana A1 - Zrenner, Rita A1 - Henze, Andrea A1 - Witzel, Katja T1 - Tissue-specific signatures of metabolites and proteins in asparagus roots and exudates JF - Horticulture research N2 - Comprehensive untargeted and targeted analysis of root exudate composition has advanced our understanding of rhizosphere processes. However, little is known about exudate spatial distribution and regulation. We studied the specific metabolite signatures of asparagus root exudates, root outer (epidermis and exodermis), and root inner tissues (cortex and vasculature). The greatest differences were found between exudates and root tissues. In total, 263 non-redundant metabolites were identified as significantly differentially abundant between the three root fractions, with the majority being enriched in the root exudate and/or outer tissue and annotated as 'lipids and lipid-like molecules' or 'phenylpropanoids and polyketides'. Spatial distribution was verified for three selected compounds using MALDI-TOF mass spectrometry imaging. Tissue-specific proteome analysis related root tissue-specific metabolite distributions and rhizodeposition with underlying biosynthetic pathways and transport mechanisms. The proteomes of root outer and inner tissues were spatially very distinct, in agreement with the fundamental differences between their functions and structures. According to KEGG pathway analysis, the outer tissue proteome was characterized by a high abundance of proteins related to 'lipid metabolism', 'biosynthesis of other secondary metabolites' and 'transport and catabolism', reflecting its main functions of providing a hydrophobic barrier, secreting secondary metabolites, and mediating water and nutrient uptake. Proteins more abundant in the inner tissue related to 'transcription', 'translation' and 'folding, sorting and degradation', in accord with the high activity of cortical and vasculature cell layers in growth- and development-related processes. In summary, asparagus root fractions accumulate specific metabolites. This expands our knowledge of tissue-specific plant cell function. Y1 - 2021 U6 - https://doi.org/10.1038/s41438-021-00510-5 SN - 2052-7276 SN - 2662-6810 VL - 8 IS - 1 PB - Nanjing Agricultural Univ. CY - Nanjing ER - TY - CHAP A1 - Löw, Martina A1 - Sayman, Volkan A1 - Schwerer, Jona A1 - Wolf, Hannah ED - Löw, Martina ED - Sayman, Volkan ED - Schwerer, Jona ED - Wolf, Hannah T1 - Am Ende der Globalisierung BT - über die Refiguration von Räumen T2 - Am Ende der Globalisierung Y1 - 2021 SN - 978-3-8394-5402-2 SN - 978-3-8376-5402-8 U6 - https://doi.org/10.14361/9783839454022 SP - 9 EP - 22 PB - transcript CY - Bielefeld ER - TY - JOUR A1 - Kapidzic, Sanja A1 - Frey, Felix A1 - Neuberger, Christoph A1 - Stieglitz, Stefan A1 - Mirbabaie, Milad T1 - Crisis communication on Twitter BT - differences between user types in top tweets about the 2015 “refugee crisis” in Germany JF - International journal of communication N2 - The study explores differences between three user types in the top tweets about the 2015 “refugee crisis” in Germany and presents the results of a quantitative content analysis. All tweets with the keyword “Flüchtlinge” posted for a monthlong period following September 13, 2015, the day Germany decided to implement border controls, were collected (N = 763,752). The top 2,495 tweets according to number of retweets were selected for analysis. Differences between news media, public and private actor tweets in topics, tweet characteristics such as tone and opinion expression, links, and specific sentiments toward refugees were analyzed. We found strong differences between the tweets. Public actor tweets were the main source of positive sentiment toward refugees and the main information source on refugee support. News media tweets mostly reflected traditional journalistic norms of impartiality and objectivity, whereas private actor tweets were more diverse in sentiments toward refugees. KW - refugee crisis 2015 KW - Germany KW - social media KW - Twitter KW - user types Y1 - 2023 UR - https://ijoc.org/index.php/ijoc/article/view/18172/4022 SN - 1932-8036 VL - 17 SP - 735 EP - 754 PB - The Annenberg Center for Communication CY - Los Angeles, Calif. ER - TY - JOUR A1 - Toumoulin, Agathe A1 - Tardif-Becquet, Delphine A1 - Donnadieu, Yannick A1 - Licht, Alexis A1 - Ladant, Jean-Baptiste A1 - Kunzmann, Lutz A1 - Dupont-Nivet, Guillaume T1 - Evolution of continental temperature seasonality from the Eocene greenhouse to the Oligocene icehouse BT - a model-data comparison JF - Climate of the past : an interactive open access journal of the European Geosciences Union N2 - At the junction of greenhouse and icehouse climate states, the Eocene-Oligocene Transition (EOT) is a key moment in Cenozoic climate history. While it is associated with severe extinctions and biodiversity turnovers on land, the role of terrestrial climate evolution remains poorly resolved, especially the associated changes in seasonality. Some paleobotanical and geochemical continental records in parts of the Northern Hemisphere suggest the EOT is associated with a marked cooling in winter, leading to the development of more pronounced seasons (i.e., an increase in the mean annual range of temperature, MATR). However, the MATR increase has been barely studied by climate models and large uncertainties remain on its origin, geographical extent and impact. In order to better understand and describe temperature seasonality changes between the middle Eocene and the early Oligocene, we use the Earth system model IPSL-CM5A2 and a set of simulations reconstructing the EOT through three major climate forcings: pCO(2) decrease (1120, 840 and 560 ppm), the Antarctic ice-sheet (AIS) formation and the associated sea-level decrease. Our simulations suggest that pCO(2) lowering alone is not sufficient to explain the seasonality evolution described by the data through the EOT but rather that the combined effects of pCO(2) , AIS formation and increased continentality provide the best data-model agreement.pCO(2) decrease induces a zonal pattern with alternating increasing and decreasing seasonality bands particularly strong in the northern high latitudes (up to 8 degrees C MATR increase) due to sea-ice and surface albedo feedback. Conversely, the onset of the AIS is responsible for a more constant surface albedo yearly, which leads to a strong decrease in seasonality in the southern midlatitudes to high latitudes (> 40 degrees S). Finally, continental areas that emerged due to the sea-level lowering cause the largest increase in seasonality and explain most of the global heterogeneity in MATR changes (1MATR) patterns. The Delta MATR patterns we reconstruct are generally consistent with the variability of the EOT biotic crisis intensity across the Northern Hemisphere and provide insights on their underlying mechanisms. Y1 - 2022 U6 - https://doi.org/10.5194/cp-18-341-2022 SN - 1814-9324 SN - 1814-9332 VL - 18 IS - 2 SP - 341 EP - 362 PB - Copernicus CY - Göttingen ER - TY - JOUR A1 - Tardif-Becquet, Delphine A1 - Fluteau, Frédéric A1 - Donnadieu, Yannick A1 - Le Hir, Guillaume A1 - Ladant, Jean-Baptiste A1 - Sepulchre, Pierre A1 - Licht, Alexis A1 - Poblete, Fernando A1 - Dupont-Nivet, Guillaume T1 - The origin of Asian monsoons BT - a modelling perspective JF - Climate of the Past N2 - The Cenozoic inception and development of the Asian monsoons remain unclear and have generated much debate, as several hypotheses regarding circulation patterns at work in Asia during the Eocene have been proposed in the few last decades. These include (a) the existence of modern-like monsoons since the early Eocene; (b) that of a weak South Asian monsoon (SAM) and little to no East Asian monsoon (EAM); or (c) a prevalence of the Intertropical Convergence Zone (ITCZ) migrations, also referred to as Indonesian-Australian monsoon (I-AM). As SAM and EAM are supposed to have been triggered or enhanced primarily by Asian palaeogeographic changes, their possible inception in the very dynamic Eocene palaeogeographic context remains an open question, both in the modelling and field-based communities. We investigate here Eocene Asian climate conditions using the IPSL-CM5A2 (Sepulchre et al., 2019) earth system model and revised palaeogeographies. Our Eocene climate simulation yields atmospheric circulation patterns in Asia substantially different from modern conditions. A large high-pressure area is simulated over the Tethys ocean, which generates intense low tropospheric winds blowing southward along the western flank of the proto-Himalayan-Tibetan plateau (HTP) system. This low-level wind system blocks, to latitudes lower than 10 degrees N, the migration of humid and warm air masses coming from the Indian Ocean. This strongly contrasts with the modern SAM, during which equatorial air masses reach a latitude of 20-25 degrees N over India and southeastern China. Another specific feature of our Eocene simulation is the widespread subsidence taking place over northern India in the midtroposphere (around 5000 m), preventing deep convective updraught that would transport water vapour up to the condensation level. Both processes lead to the onset of a broad arid region located over northern India and over the HTP. More humid regions of high seasonality in precipitation encircle this arid area, due to the prevalence of the Intertropical Convergence Zone (ITCZ) migrations (or Indonesian-Australian monsoon, I-AM) rather than monsoons. Although the existence of this central arid region may partly result from the specifics of our simulation (model dependence and palaeogeographic uncertainties) and has yet to be confirmed by proxy records, most of the observational evidence for Eocene monsoons are located in the highly seasonal transition zone between the arid area and the more humid surroundings. We thus suggest that a zonal arid climate prevailed over Asia before the initiation of monsoons that most likely occurred following Eocene palaeogeographic changes. Our results also show that precipitation seasonality should be used with caution to infer the presence of a monsoonal circulation and that the collection of new data in this arid area is of paramount importance to allow the debate to move forward. KW - earth system model KW - early eocene KW - tibetan plateau KW - climate-change KW - oligocene climate KW - summer monsoon KW - global monsoon KW - ice sheet KW - part 1 KW - China Y1 - 2020 U6 - https://doi.org/10.5194/cp-16-847-2020 SN - 1814-9332 SN - 1814-9324 VL - 16 IS - 3 SP - 847 EP - 865 PB - Copernicus Publications CY - Göttingen ER - TY - JOUR A1 - König, Johanna A1 - Block, Andrea A1 - Becker, Mathias A1 - Fenske, Kristin A1 - Hertel, Johannes A1 - Van der Auwera, Sandra A1 - Zymara, Kathleen A1 - Voelzke, Henry A1 - Freyberger, Harald Jürgen A1 - Grabe, Hans Joergen T1 - Assessment of subjective emotional valence and long-lasting impact of life events BT - development and psychometrics of the Stralsund Life Event List (SEL) JF - BMC Psychiatry N2 - Background: Life events (LEs) are associated with future physical and mental health. They are crucial for understanding the pathways to mental disorders as well as the interactions with biological parameters. However, deeper insight is needed into the complex interplay between the type of LE, its subjective evaluation and accompanying factors such as social support. The "Stralsund Life Event List" (SEL) was developed to facilitate this research. Methods: The SEL is a standardized interview that assesses the time of occurrence and frequency of 81 LEs, their subjective emotional valence, the perceived social support during the LE experience and the impact of past LEs on present life. Data from 2265 subjects from the general population-based cohort study "Study of Health in Pomerania" (SHIP) were analysed. Based on the mean emotional valence ratings of the whole sample, LEs were categorized as "positive" or "negative". For verification, the SEL was related to lifetime major depressive disorder (MDD; Munich Composite International Diagnostic Interview), childhood trauma (Childhood Trauma Questionnaire), resilience (Resilience Scale) and subjective health (SF-12 Health Survey). Conclusions: The SEL is a valid instrument that enables the analysis of the number and frequency of LEs, their emotional valence, perceived social support and current impact on life on a global score and on an individual item level. Thus, we can recommend its use in research settings that require the assessment and analysis of the relationship between the occurrence and subjective evaluation of LEs as well as the complex balance between distressing and stabilizing life experiences. KW - Positive life events KW - Negative life events KW - General population KW - Emotional valence KW - Depressive disorder Y1 - 2018 U6 - https://doi.org/10.1186/s12888-018-1649-3 SN - 1471-244X VL - 18 PB - BioMed Central CY - London ER - TY - JOUR A1 - Herrmann, Matthias L. A1 - Boden, Cindy A1 - Maurer, Christoph A1 - Kentischer, Felix A1 - Mennig, Eva A1 - Wagner, Sören A1 - Conzelmann, Lars O. A1 - Förstner, Bernd R. A1 - Rapp, Michael A. A1 - von Arnim, Christine A. F. A1 - Denkinger, Michael A1 - Eschweiler, Gerhard W. A1 - Thomas, Christine T1 - Anticholinergic drug exposure increases the risk of delirium in older patients undergoing elective surgery JF - Frontiers in medicine N2 - IntroductionPostoperative delirium (POD) is a common and serious adverse event of surgery in older people. Because of its great impact on patients' safety and quality of life, identification of modifiable risk factors could be useful. Although preoperative medication intake is assumed to be an important modifiable risk factor, the impact of anticholinergic drugs on the occurrence of POD seems underestimated in elective surgery. The aim of this study was to investigate the association between preoperative anticholinergic burden and POD. We hypothesized that a high preoperative anticholinergic burden is an independent, potentially modifiable predisposing and precipitating factor of POD in older people. MethodsBetween November 2017 and April 2019, 1,470 patients of 70 years and older undergoing elective orthopedic, general, cardiac, or vascular surgery were recruited in the randomized, prospective, multicenter PAWEL trial. Anticholinergic burden of a sub-cohort of 899 patients, who did not receive a multimodal intervention for preventing POD, was assessed by two different tools at hospital admission: The established Anticholinergic Risk Scale (ARS) and the recently developed Anticholinergic Burden Score (ABS). POD was detected by confusion assessment method (CAM) and a validated post discharge medical record review. Logistic regression analyses were performed to evaluate the association between anticholinergic burden and POD. ResultsPOD was observed in 210 of 899 patients (23.4%). Both ARS and ABS were independently associated with POD. The association persisted after adjustment for relevant confounding factors such as age, sex, comorbidities, preoperative cognitive and physical status, number of prescribed drugs, surgery time, type of surgery and anesthesia, usage of heart-lung-machine, and treatment in intensive care unit. If a patient was taking one of the 56 drugs listed in the ABS, risk for POD was 2.7-fold higher (OR = 2.74, 95% CI = 1.55-4.94) and 1.5-fold higher per additional point on the ARS (OR = 1.54, 95% CI = 1.15-2.02). ConclusionPreoperative anticholinergic drug exposure measured by ARS or ABS was independently associated with POD in older patients undergoing elective surgery. Therefore, identification, discontinuation or substitution of anticholinergic medication prior to surgery may be a promising approach to reduce the risk of POD in older patients. KW - delirium KW - acute encephalopathy KW - surgery KW - anticholinergic KW - geriatric KW - postoperative Y1 - 2022 U6 - https://doi.org/10.3389/fmed.2022.871229 SN - 2296-858X VL - 9 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Haugk, Charlotte A1 - Jongejans, Loeka L. A1 - Mangelsdorf, Kai A1 - Fuchs, Matthias A1 - Ogneva, Olga A1 - Palmtag, Juri A1 - Mollenhauer, Gesine A1 - Mann, Paul J. A1 - Overduin, P. Paul A1 - Grosse, Guido A1 - Sanders, Tina A1 - Tuerena, Robyn E. A1 - Schirrmeister, Lutz A1 - Wetterich, Sebastian A1 - Kizyakov, Alexander A1 - Karger, Cornelia A1 - Strauss, Jens T1 - Organic matter characteristics of a rapidly eroding permafrost cliff in NE Siberia (Lena Delta, Laptev Sea region) JF - Biogeosciences N2 - Organic carbon (OC) stored in Arctic permafrost represents one of Earth's largest and most vulnerable terrestrial carbon pools. Amplified climate warming across the Arctic results in widespread permafrost thaw. Permafrost deposits exposed at river cliffs and coasts are particularly susceptible to thawing processes. Accelerating erosion of terrestrial permafrost along shorelines leads to increased transfer of organic matter (OM) to nearshore waters. However, the amount of terrestrial permafrost carbon and nitrogen as well as the OM quality in these deposits is still poorly quantified. We define the OM quality as the intrinsic potential for further transformation, decomposition and mineralisation. Here, we characterise the sources and the quality of OM supplied to the Lena River at a rapidly eroding permafrost river shoreline cliff in the eastern part of the delta (Sobo-Sise Island). Our multi-proxy approach captures bulk elemental, molecu- lar geochemical and carbon isotopic analyses of Late Pleistocene Yedoma permafrost and Holocene cover deposits, discontinuously spanning the last similar to 52 kyr. We showed that the ancient permafrost exposed in the Sobo-Sise cliff has a high organic carbon content (mean of about 5 wt %). The oldest sediments stem from Marine Isotope Stage (MIS) 3 interstadial deposits (dated to 52 to 28 cal ka BP) and are overlaid by last glacial MIS 2 (dated to 28 to 15 cal ka BP) and Holocene MIS 1 (dated to 7-0 cal ka BP) deposits. The relatively high average chain length (ACL) index of n-alkanes along the cliff profile indicates a predominant contribution of vascular plants to the OM composition. The elevated ratio of isoand anteiso-branched fatty acids (FAs) relative to mid- and long-chain (C >= 20) n-FAs in the interstadial MIS 3 and the interglacial MIS 1 deposits suggests stronger microbial activity and consequently higher input of bacterial biomass during these climatically warmer periods. The overall high carbon preference index (CPI) and higher plant fatty acid (HPFA) values as well as high C/N ratios point to a good quality of the preserved OM and thus to a high potential of the OM for decomposition upon thaw. A decrease in HPFA values downwards along the profile probably indicates stronger OM decomposition in the oldest (MIS 3) deposits of the cliff. The characterisation of OM from eroding permafrost leads to a better assessment of the greenhouse gas potential of the OC released into river and nearshore waters in the future. Y1 - 2022 U6 - https://doi.org/10.5194/bg-19-2079-2022 SN - 1726-4170 SN - 1726-4189 VL - 19 IS - 7 SP - 2079 EP - 2094 PB - Copernicus CY - Göttingen ER -