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- Strukturbereich Kognitionswissenschaften (31)
Gorski, Mathias ; Jung, Bettina ; Li, Yong ; Matias-Garcia, Pamela R. ; Wuttke, Matthias ; Coassin, Stefan ; Thio, Chris H. L. ; Kleber, Marcus E. ; Winkler, Thomas W. ; Wanner, Veronika ; Chai, Jin-Fang ; Chu, Audrey Y. ; Cocca, Massimiliano ; Feitosa, Mary F. ; Ghasemi, Sahar ; Hoppmann, Anselm ; Horn, Katrin ; Li, Man ; Nutile, Teresa ; Scholz, Markus ; Sieber, Karsten B. ; Teumer, Alexander ; Tin, Adrienne ; Wang, Judy ; Tayo, Bamidele O. ; Ahluwalia, Tarunveer S. ; Almgren, Peter ; Bakker, Stephan J. L. ; Banas, Bernhard ; Bansal, Nisha ; Biggs, Mary L. ; Boerwinkle, Eric ; Böttinger, Erwin ; Brenner, Hermann ; Carroll, Robert J. ; Chalmers, John ; Chee, Miao-Li ; Chee, Miao-Ling ; Cheng, Ching-Yu ; Coresh, Josef ; de Borst, Martin H. ; Degenhardt, Frauke ; Eckardt, Kai-Uwe ; Endlich, Karlhans ; Franke, Andre ; Freitag-Wolf, Sandra ; Gampawar, Piyush ; Gansevoort, Ron T. ; Ghanbari, Mohsen ; Gieger, Christian ; Hamet, Pavel ; Ho, Kevin ; Hofer, Edith ; Holleczek, Bernd ; Foo, Valencia Hui Xian ; Hutri-Kahonen, Nina ; Hwang, Shih-Jen ; Ikram, M. Arfan ; Josyula, Navya Shilpa ; Kahonen, Mika ; Khor, Chiea-Chuen ; Koenig, Wolfgang ; Kramer, Holly ; Kraemer, Bernhard K. ; Kuehnel, Brigitte ; Lange, Leslie A. ; Lehtimaki, Terho ; Lieb, Wolfgang ; Loos, Ruth J. F. ; Lukas, Mary Ann ; Lyytikainen, Leo-Pekka ; Meisinger, Christa ; Meitinger, Thomas ; Melander, Olle ; Milaneschi, Yuri ; Mishra, Pashupati P. ; Mononen, Nina ; Mychaleckyj, Josyf C. ; Nadkarni, Girish N. ; Nauck, Matthias ; Nikus, Kjell ; Ning, Boting ; Nolte, Ilja M. ; O'Donoghue, Michelle L. ; Orho-Melander, Marju ; Pendergrass, Sarah A. ; Penninx, Brenda W. J. H. ; Preuss, Michael H. ; Psaty, Bruce M. ; Raffield, Laura M. ; Raitakari, Olli T. ; Rettig, Rainer ; Rheinberger, Myriam ; Rice, Kenneth M. ; Rosenkranz, Alexander R. ; Rossing, Peter ; Rotter, Jerome ; Sabanayagam, Charumathi ; Schmidt, Helena ; Schmidt, Reinhold ; Schoettker, Ben ; Schulz, Christina-Alexandra ; Sedaghat, Sanaz ; Shaffer, Christian M. ; Strauch, Konstantin ; Szymczak, Silke ; Taylor, Kent D. ; Tremblay, Johanne ; Chaker, Layal ; van der Harst, Pim ; van der Most, Peter J. ; Verweij, Niek ; Voelker, Uwe ; Waldenberger, Melanie ; Wallentin, Lars ; Waterworth, Dawn M. ; White, Harvey D. ; Wilson, James G. ; Wong, Tien-Yin ; Woodward, Mark ; Yang, Qiong ; Yasuda, Masayuki ; Yerges-Armstrong, Laura M. ; Zhang, Yan ; Snieder, Harold ; Wanner, Christoph ; Boger, Carsten A. ; Kottgen, Anna ; Kronenberg, Florian ; Pattaro, Cristian ; Heid, Iris M.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Metabolic signatures of healthy lifestyle patterns and colorectal cancer risk in a European cohort
(2020)
Rothwell, Joseph A. ; Murphy, Neil ; Aleksandrova, Krasimira ; Schulze, Matthias Bernd ; Bešević, Jelena ; Kliemann, Nathalie ; Jenab, Mazda ; Ferrari, Pietro ; Achaintre, David ; Gicquiau, Audrey ; Vozar, Béatrice ; Scalbert, Augustin ; Huybrechts, Inge ; Freisling, Heinz ; Prehn, Cornelia ; Adamski, Jerzy ; Cross, Amanda J. ; Pala, Valeria Maria ; Boutron-Ruault, Marie-Christine ; Dahm, Christina C. ; Overvad, Kim ; Gram, Inger Torhild ; Sandanger, Torkjel M. ; Skeie, Guri ; Jakszyn, Paula ; Tsilidis, Kostas K. ; Hughes, David J. ; van Guelpen, Bethany ; Bodén, Stina ; Sánchez, Maria-José ; Schmidt, Julie A. ; Katzke, Verena ; Kühn, Tilman ; Colorado-Yohar, Sandra ; Tumino, Rosario ; Bueno-de-Mesquita, Bas ; Vineis, Paolo ; Masala, Giovanna ; Panico, Salvatore ; Eriksen, Anne Kirstine ; Tjønneland, Anne ; Aune, Dagfinn ; Weiderpass, Elisabete ; Severi, Gianluca ; Chajès, Véronique ; Gunter, Marc J.
BACKGROUND & AIMS: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.
METHODS: Scores reflecting adherence to the WCRF/AICR recommendations (scale, 1-5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer and Nutrition participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression.
RESULTS: Higher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95% CI, 0.29-0.90; endogenous metabolites: OR, 0.62 per unit change; 95% CI, 0.50-0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95% CI, 0.86-1.00) overall. Signature associations were stronger in male compared with female participants.
CONCLUSIONS: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.
Barbolini, Natasha ; Woutersen, Amber ; Dupont-Nivet, Guillaume ; Silvestro, Daniele ; Tardif-Becquet, Delphine ; Coster, Pauline M. C. ; Meijer, Niels ; Chang, Cun ; Zhang, Hou-Xi ; Licht, Alexis ; Rydin, Catarina ; Koutsodendris, Andreas ; Han, Fang ; Rohrmann, Alexander ; Liu, Xiang-Jun ; Zhang, Y. ; Donnadieu, Yannick ; Fluteau, Frederic ; Ladant, Jean-Baptiste ; Le Hir, Guillaume ; Hoorn, M. Carina
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.
Vaid, Akhil ; Somani, Sulaiman ; Russak, Adam J. ; De Freitas, Jessica K. ; Chaudhry, Fayzan F. ; Paranjpe, Ishan ; Johnson, Kipp W. ; Lee, Samuel J. ; Miotto, Riccardo ; Richter, Felix ; Zhao, Shan ; Beckmann, Noam D. ; Naik, Nidhi ; Kia, Arash ; Timsina, Prem ; Lala, Anuradha ; Paranjpe, Manish ; Golden, Eddye ; Danieletto, Matteo ; Singh, Manbir ; Meyer, Dara ; O'Reilly, Paul F. ; Huckins, Laura ; Kovatch, Patricia ; Finkelstein, Joseph ; Freeman, Robert M. ; Argulian, Edgar ; Kasarskis, Andrew ; Percha, Bethany ; Aberg, Judith A. ; Bagiella, Emilia ; Horowitz, Carol R. ; Murphy, Barbara ; Nestler, Eric J. ; Schadt, Eric E. ; Cho, Judy H. ; Cordon-Cardo, Carlos ; Fuster, Valentin ; Charney, Dennis S. ; Reich, David L. ; Böttinger, Erwin ; Levin, Matthew A. ; Narula, Jagat ; Fayad, Zahi A. ; Just, Allan C. ; Charney, Alexander W. ; Nadkarni, Girish N. ; Glicksberg, Benjamin S.
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.
Abdalla, H. ; Adam, R. ; Aharonian, Felix A. ; Benkhali, F. Ait ; Angüner, Ekrem Oǧuzhan ; Arcaro, C. ; Armand, C. ; Armstrong, T. ; Ashkar, H. ; Backes, M. ; Baghmanyan, V. ; Martins, V. Barbosa ; Barnacka, A. ; Barnard, M. ; Becherini, Y. ; Berge, D. ; Bernlohr, K. ; Bi, B. ; Bottcher, M. ; Boisson, C. ; Bolmont, J. ; de Lavergne, M. de Bony ; Bordas, Pol ; Breuhaus, M. ; Brun, F. ; Brun, P. ; Bryan, M. ; Buchele, M. ; Bulik, T. ; Bylund, T. ; Caroff, S. ; Carosi, A. ; Casanova, Sabrina ; Chand, T. ; Chandra, S. ; Chen, A. ; Cotter, G. ; Curylo, M. ; Mbarubucyeye, J. Damascene ; Davids, I. D. ; Davies, J. ; Deil, C. ; Devin, J. ; deWilt, P. ; Dirson, L. ; Djannati-Atai, A. ; Dmytriiev, A. ; Donath, A. ; Doroshenko, V. ; Duffy, C. ; Dyks, J. ; Egberts, Kathrin ; Eichhorn, F. ; Einecke, S. ; Emery, G. ; Ernenwein, J. -P. ; Feijen, K. ; Fegan, S. ; Fiasson, A. ; de Clairfontaine, G. Fichet ; Fontaine, G. ; Funk, S. ; Fussling, Matthias ; Gabici, S. ; Gallant, Y. A. ; Giavitto, G. ; Giunti, L. ; Glawion, D. ; Glicenstein, J. F. ; Gottschall, D. ; Grondin, M. -H. ; Hahn, J. ; Haupt, M. ; Hermann, G. ; Hinton, J. A. ; Hofmann, W. ; Hoischen, Clemens ; Holch, T. L. ; Holler, M. ; Horbe, M. ; Horns, D. ; Huber, D. ; Jamrozy, M. ; Jankowsky, D. ; Jankowsky, F. ; Jardin-Blicq, A. ; Joshi, V. ; Jung-Richardt, I. ; Kasai, E. ; Kastendieck, M. A. ; Katarzynski, K. ; Katz, U. ; Khangulyan, D. ; Khelifi, B. ; Klepser, S. ; Kluzniak, W. ; Komin, Nu. ; Konno, R. ; Kosack, K. ; Kostunin, D. ; Kreter, M. ; Lamanna, G. ; Lemiere, A. ; Lemoine-Goumard, M. ; Lenain, J. -P. ; Levy, C. ; Lohse, T. ; Lypova, I. ; Mackey, J. ; Majumdar, J. ; Malyshev, D. ; Malyshev, D. ; Marandon, V. ; Marchegiani, P. ; Marcowith, Alexandre ; Mares, A. ; Marti-Devesa, G. ; Marx, R. ; Maurin, G. ; Meintjes, P. J. ; Meyer, M. ; Mitchell, A. ; Moderski, R. ; Mohamed, M. ; Mohrmann, L. ; Montanari, A. ; Moore, C. ; Morris, P. ; Moulin, Emmanuel ; Muller, J. ; Murach, T. ; Nakashima, K. ; Nayerhoda, A. ; de Naurois, M. ; Ndiyavala, H. ; Niederwanger, F. ; Niemiec, J. ; Oakes, L. ; O'Brien, Patrick ; Odaka, H. ; Ohm, S. ; Olivera-Nieto, L. ; Wilhelmi, E. de Ona ; Ostrowski, M. ; Oya, I. ; Panter, M. ; Panny, S. ; Parsons, R. D. ; Peron, G. ; Peyaud, B. ; Piel, Q. ; Pita, S. ; Poireau, V. ; Noel, A. Priyana ; Prokhorov, D. A. ; Prokoph, H. ; Puhlhofer, G. ; Punch, M. ; Quirrenbach, A. ; Raab, S. ; Rauth, R. ; Reichherzer, P. ; Reimer, A. ; Reimer, O. ; Remy, Q. ; Renaud, M. ; Rieger, F. ; Rinchiuso, L. ; Romoli, C. ; Rowell, G. ; Rudak, B. ; Ruiz-Velasco, E. ; Sahakian, V. ; Sailer, S. ; Sanchez, D. A. ; Santangelo, Andrea ; Sasaki, M. ; Scalici, M. ; Schussler, F. ; Schutte, H. M. ; Schwanke, U. ; Schwemmer, S. ; Seglar-Arroyo, M. ; Senniappan, M. ; Seyffert, A. S. ; Shafi, N. ; Shiningayamwe, K. ; Simoni, R. ; Sinha, A. ; Sol, H. ; Specovius, A. ; Spencer, S. ; Spir-Jacob, M. ; Stawarz, L. ; Sun, L. ; Steenkamp, R. ; Stegmann, C. ; Steinmassl, S. ; Steppa, C. ; Takahashi, T. ; Tavernier, T. ; Taylor, A. M. ; Terrier, R. ; Tiziani, D. ; Tluczykont, M. ; Tomankova, L. ; Trichard, C. ; Tsirou, M. ; Tuffs, R. ; Uchiyama, Y. ; van der Walt, D. J. ; van Eldik, C. ; van Rensburg, C. ; van Soelen, B. ; Vasileiadis, G. ; Veh, J. ; Venter, C. ; Vincent, P. ; Vink, J. ; Volk, H. J. ; Vuillaume, T. ; Wadiasingh, Z. ; Wagner, S. J. ; Watson, J. ; Werner, F. ; White, R. ; Wierzcholska, A. ; Wong, Yu Wun ; Yusafzai, A. ; Zacharias, M. ; Zanin, R. ; Zargaryan, D. ; Zdziarski, A. A. ; Zech, Alraune ; Zhu, S. J. ; Ziegler, A. ; Zorn, J. ; Zouari, S. ; Zywucka, N.
The unidentified very-high-energy (VHE; E > 0.1 TeV) gamma -ray source, HESS J1826-130, was discovered with the High Energy Stereoscopic System (HESS) in the Galactic plane. The analysis of 215 h of HESS data has revealed a steady gamma -ray flux from HESS J1826-130, which appears extended with a half-width of 0.21 degrees +/- 0.02 <br /> (stat)degrees <br /> stat degrees +/- 0.05 <br /> (sys)degrees sys degrees . The source spectrum is best fit with either a power-law function with a spectral index Gamma = 1.78 +/- 0.10(stat) +/- 0.20(sys) and an exponential cut-off at 15.2 <br /> (+5.5)(-3.2) -3.2+5.5 TeV, or a broken power-law with Gamma (1) = 1.96 +/- 0.06(stat) +/- 0.20(sys), Gamma (2) = 3.59 +/- 0.69(stat) +/- 0.20(sys) for energies below and above E-br = 11.2 +/- 2.7 TeV, respectively. The VHE flux from HESS J1826-130 is contaminated by the extended emission of the bright, nearby pulsar wind nebula, HESS J1825-137, particularly at the low end of the energy spectrum. Leptonic scenarios for the origin of HESS J1826-130 VHE emission related to PSR J1826-1256 are confronted by our spectral and morphological analysis. In a hadronic framework, taking into account the properties of dense gas regions surrounding HESS J1826-130, the source spectrum would imply an astrophysical object capable of accelerating the parent particle population up to greater than or similar to 200 TeV. Our results are also discussed in a multiwavelength context, accounting for both the presence of nearby supernova remnants, molecular clouds, and counterparts detected in radio, X-rays, and TeV energies.
Gorski, Mathias ; Jung, Bettina ; Li, Yong ; Matias-Garcia, Pamela R. ; Wuttke, Matthias ; Coassin, Stefan ; Thio, Chris H. L. ; Kleber, Marcus E. ; Winkler, Thomas W. ; Wanner, Veronika ; Chai, Jin-Fang ; Chu, Audrey Y. ; Cocca, Massimiliano ; Feitosa, Mary F. ; Ghasemi, Sahar ; Hoppmann, Anselm ; Horn, Katrin ; Li, Man ; Nutile, Teresa ; Scholz, Markus ; Sieber, Karsten B. ; Teumer, Alexander ; Tin, Adrienne ; Wang, Judy ; Tayo, Bamidele O. ; Ahluwalia, Tarunveer S. ; Almgren, Peter ; Bakker, Stephan J. L. ; Banas, Bernhard ; Bansal, Nisha ; Biggs, Mary L. ; Boerwinkle, Eric ; Böttinger, Erwin ; Brenner, Hermann ; Carroll, Robert J. ; Chalmers, John ; Chee, Miao-Li ; Chee, Miao-Ling ; Cheng, Ching-Yu ; Coresh, Josef ; de Borst, Martin H. ; Degenhardt, Frauke ; Eckardt, Kai-Uwe ; Endlich, Karlhans ; Franke, Andre ; Freitag-Wolf, Sandra ; Gampawar, Piyush ; Gansevoort, Ron T. ; Ghanbari, Mohsen ; Gieger, Christian ; Hamet, Pavel ; Ho, Kevin ; Hofer, Edith ; Holleczek, Bernd ; Foo, Valencia Hui Xian ; Hutri-Kahonen, Nina ; Hwang, Shih-Jen ; Ikram, M. Arfan ; Josyula, Navya Shilpa ; Kahonen, Mika ; Khor, Chiea-Chuen ; Koenig, Wolfgang ; Kramer, Holly ; Kraemer, Bernhard K. ; Kuehnel, Brigitte ; Lange, Leslie A. ; Lehtimaki, Terho ; Lieb, Wolfgang ; Loos, Ruth J. F. ; Lukas, Mary Ann ; Lyytikainen, Leo-Pekka ; Meisinger, Christa ; Meitinger, Thomas ; Melander, Olle ; Milaneschi, Yuri ; Mishra, Pashupati P. ; Mononen, Nina ; Mychaleckyj, Josyf C. ; Nadkarni, Girish N. ; Nauck, Matthias ; Nikus, Kjell ; Ning, Boting ; Nolte, Ilja M. ; O'Donoghue, Michelle L. ; Orho-Melander, Marju ; Pendergrass, Sarah A. ; Penninx, Brenda W. J. H. ; Preuss, Michael H. ; Psaty, Bruce M. ; Raffield, Laura M. ; Raitakari, Olli T. ; Rettig, Rainer ; Rheinberger, Myriam ; Rice, Kenneth M. ; Rosenkranz, Alexander R. ; Rossing, Peter ; Rotter, Jerome ; Sabanayagam, Charumathi ; Schmidt, Helena ; Schmidt, Reinhold ; Schoettker, Ben ; Schulz, Christina-Alexandra ; Sedaghat, Sanaz ; Shaffer, Christian M. ; Strauch, Konstantin ; Szymczak, Silke ; Taylor, Kent D. ; Tremblay, Johanne ; Chaker, Layal ; van der Harst, Pim ; van der Most, Peter J. ; Verweij, Niek ; Voelker, Uwe ; Waldenberger, Melanie ; Wallentin, Lars ; Waterworth, Dawn M. ; White, Harvey D. ; Wilson, James G. ; Wong, Tien-Yin ; Woodward, Mark ; Yang, Qiong ; Yasuda, Masayuki ; Yerges-Armstrong, Laura M. ; Zhang, Yan ; Snieder, Harold ; Wanner, Christoph ; Boger, Carsten A. ; Kottgen, Anna ; Kronenberg, Florian ; Pattaro, Cristian ; Heid, Iris M.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Deng, Zijun ; Wang, Weiwei ; Xua, Xun ; Gould, Oliver E. C. ; Kratz, Karl ; Ma, Nan ; Lendlein, Andreas
Stem cells are capable of sensing and processing environmental inputs, converting this information to output a specific cell lineage through signaling cascades. Despite the combinatorial nature of mechanical, thermal, and biochemical signals, these stimuli have typically been decoupled and applied independently, requiring continuous regulation by controlling units. We employ a programmable polymer actuator sheet to autonomously synchronize thermal and mechanical signals applied to mesenchymal stem cells (MSC5). Using a grid on its underside, the shape change of polymer sheet, as well as cell morphology, calcium (Ca2+) influx, and focal adhesion assembly, could be visualized and quantified. This paper gives compelling evidence that the temperature sensing and mechanosensing of MSC5 are interconnected via intracellular Ca2+. Up-regulated Ca2+ levels lead to a remarkable alteration of histone H3K9 acetylation and activation of osteogenic related genes. The interplay of physical, thermal, and biochemical signaling was utilized to accelerate the cell differentiation toward osteogenic lineage. The approach of programmable bioinstructivity provides a fundamental principle for functional biomaterials exhibiting multifaceted stimuli on differentiation programs. Technological impact is expected in the tissue engineering of periosteum for treating bone defects.
van Rees, Charles B. ; Waylen, Kerry A. ; Schmidt-Kloiber, Astrid ; Thackeray, Stephen J. ; Kalinkat, Gregor ; Martens, Koen ; Domisch, Sami ; Lillebo, Ana ; Hermoso, Virgilio ; Grossart, Hans-Peter ; Schinegger, Rafaela ; Decleer, Kris ; Adriaens, Tim ; Denys, Luc ; Jaric, Ivan ; Janse, Jan H. ; Monaghan, Michael T. ; De Wever, Aaike ; Geijzendorffer, Ilse ; Adamescu, Mihai C. ; Jähnig, Sonja C.
Plans are currently being drafted for the next decade of action on biodiversity-both the post-2020 Global Biodiversity Framework of the Convention on Biological Diversity (CBD) and Biodiversity Strategy of the European Union (EU). Freshwater biodiversity is disproportionately threatened and underprioritized relative to the marine and terrestrial biota, despite supporting a richness of species and ecosystems with their own intrinsic value and providing multiple essential ecosystem services. Future policies and strategies must have a greater focus on the unique ecology of freshwater life and its multiple threats, and now is a critical time to reflect on how this may be achieved. We identify priority topics including environmental flows, water quality, invasive species, integrated water resources management, strategic conservation planning, and emerging technologies for freshwater ecosystem monitoring. We synthesize these topics with decades of first-hand experience and recent literature into 14 special recommendations for global freshwater biodiversity conservation based on the successes and setbacks of European policy, management, and research. Applying and following these recommendations will inform and enhance the ability of global and European post-2020 biodiversity agreements to halt and reverse the rapid global decline of freshwater biodiversity.
ISMIP6 Antarctica
(2020)
Seroussi, Helene ; Nowicki, Sophie ; Payne, Antony J. ; Goelzer, Heiko ; Lipscomb, William H. ; Abe-Ouchi, Ayako ; Agosta, Cecile ; Albrecht, Torsten ; Asay-Davis, Xylar ; Barthel, Alice ; Calov, Reinhard ; Cullather, Richard ; Dumas, Christophe ; Galton-Fenzi, Benjamin K. ; Gladstone, Rupert ; Golledge, Nicholas R. ; Gregory, Jonathan M. ; Greve, Ralf ; Hattermann, Tore ; Hoffman, Matthew J. ; Humbert, Angelika ; Huybrechts, Philippe ; Jourdain, Nicolas C. ; Kleiner, Thomas ; Larour, Eric ; Leguy, Gunter R. ; Lowry, Daniel P. ; Little, Chistopher M. ; Morlighem, Mathieu ; Pattyn, Frank ; Pelle, Tyler ; Price, Stephen F. ; Quiquet, Aurelien ; Reese, Ronja ; Schlegel, Nicole-Jeanne ; Shepherd, Andrew ; Simon, Erika ; Smith, Robin S. ; Straneo, Fiammetta ; Sun, Sainan ; Trusel, Luke D. ; Van Breedam, Jonas ; van de Wal, Roderik S. W. ; Winkelmann, Ricarda ; Zhao, Chen ; Zhang, Tong ; Zwinger, Thomas
Ice flow models of the Antarctic ice sheet are commonly used to simulate its future evolution in response to different climate scenarios and assess the mass loss that would contribute to future sea level rise. However, there is currently no consensus on estimates of the future mass balance of the ice sheet, primarily because of differences in the representation of physical processes, forcings employed and initial states of ice sheet models. This study presents results from ice flow model simulations from 13 international groups focusing on the evolution of the Antarctic ice sheet during the period 2015-2100 as part of the Ice Sheet Model Intercomparison for CMIP6 (ISMIP6). They are forced with outputs from a subset of models from the Coupled Model Intercomparison Project Phase 5 (CMIP5), representative of the spread in climate model results. Simulations of the Antarctic ice sheet contribution to sea level rise in response to increased warming during this period varies between 7:8 and 30.0 cm of sea level equivalent (SLE) under Representative Concentration Pathway (RCP) 8.5 scenario forcing. These numbers are relative to a control experiment with constant climate conditions and should therefore be added to the mass loss contribution under climate conditions similar to present-day conditions over the same period. The simulated evolution of the West Antarctic ice sheet varies widely among models, with an overall mass loss, up to 18.0 cm SLE, in response to changes in oceanic conditions. East Antarctica mass change varies between 6 :1 and 8.3 cm SLE in the simulations, with a significant increase in surface mass balance outweighing the increased ice discharge under most RCP 8.5 scenario forcings. The inclusion of ice shelf collapse, here assumed to be caused by large amounts of liquid water ponding at the surface of ice shelves, yields an additional simulated mass loss of 28mm compared to simulations without ice shelf collapse. The largest sources of uncertainty come from the climate forcing, the ocean-induced melt rates, the calibration of these melt rates based on oceanic conditions taken outside of ice shelf cavities and the ice sheet dynamic response to these oceanic changes. Results under RCP 2.6 scenario based on two CMIP5 climate models show an additional mass loss of 0 and 3 cm of SLE on average compared to simulations done under present-day conditions for the two CMIP5 forcings used and display limited mass gain in East Antarctica.
Kühne, Franziska ; Fauth, Henriette ; Destina Sevde, Ay-Bryson ; Visser, Leonie N.C. ; Weck, Florian
Background
Communicating a diagnosis is highly important, yet complex, especially in the context of cancer and mental disorders. The aim was to explore the communication style of an oncologist vs. psychotherapist in an online study.
Methods
Patients (N = 136: 65 cancer, 71 depression) were randomly assigned to watch a standardized video vignette with one of two communication styles (empathic vs. unempathic). Outcome measures of affectivity, information recall, communication skills, empathy and trust were applied.
Results
Regardless of diagnosis, empathic communication was associated with the perception of a significantly more empathic (p < 0.001, η2partial = 0.08) and trustworthy practitioner (p = 0.014, η2partial = 0.04) with better communication skills (p = 0.013, η2partial = 0.05). Cancer patients reported a larger decrease in positive affect (p < 0.001, η2partial = 0.15) and a larger increase in negative affect (p < 0.001, η2partial = 0.14) from pre- to post-video than depressive patients. Highly relevant information was recalled better in both groups (p < 0.001, d = 0.61–1.06).
Conclusions
The results highlight the importance of empathy while communicating both a diagnosis of cancer and a mental disorder. Further research should focus on the communication of a mental disorder in association with cancer.
Schenck, Marcia C. ; Mohamed Zakaria, Abdalla ; Ndiritiro, Richesse ; Omar, Shaema ; Rer, Samson ; Reed, Kate ; Teferra, Gerawork
While academic mobility has generally been positioned in the literature as a ready, at-will movement of people and ideas, this chapter demonstrates how the conditions of mobility and immobility “all at once” impact knowledge production and exchange. By offering a more nuanced window into the experiences of scholars in exile, this chapter challenges dominant discourses of academic mobility and draws on lessons learned from within liminal spaces of knowledge production to elicit more response within higher education communities. Context-rich examples reveal the interpersonal tensions and cultural shifts—including gender, ethnic and race-based stereotypes and discrimination—that affect intellectual outputs, further problematizing the conceptualization of knowledge production in human capital terms. Lessons gleaned from Scholars at Risk (SAR) and related programmes suggest support structures that amplify scholars’ agency; more broadly, higher education should consider ways of adapting to its diverse knowledge producers, rather than supporting the acclimation to its current environment.
Deconstructing the Gestalt
(2021)
Snakes-a subset of lizards-have traditionally been divided into two major groups based on feeding mechanics: "macrostomy," involving the ingestion of proportionally large prey items; and "microstomy," the lack of this ability. "Microstomy"-considered present in scolecophidian and early-diverging alethinophidian snakes-is generally viewed as a symplesiomorphy shared with non-snake lizards. However, this perspective of "microstomy" as plesiomorphic and morphologically homogenous fails to recognize the complexity of this condition and its evolution across "microstomatan" squamates. To challenge this problematic paradigm, we formalize a new framework for conceptualizing and testing the homology of overall character complexes, or "morphotypes," which underlies our re-assessment of "microstomy." Using micro-computed tomography (micro-CT) scans, we analyze the morphology of the jaws and suspensorium across purported "microstomatan" squamates (scolecophidians, early-diverging alethinophidians, and non-snake lizards) and demonstrate that key components of the jaw complex are not homologous at the level of primary character state identity across these taxa. Therefore, rather than treating "microstomy" as a uniform condition, we instead propose that non-snake lizards, early-diverging alethinophidians, anomalepidids, leptotyphlopids, and typhlopoids each exhibit a unique and nonhomologous jaw morphotype: "minimal-kinesis microstomy," "snout-shifting," "axle-brace maxillary raking," "mandibular raking," and "single-axle maxillary raking," respectively. The lack of synapomorphy among scolecophidians is inconsistent with the notion of scolecophidians representing an ancestral snake condition, and instead reflects a hypothesis of the independent evolution of fossoriality, miniaturization, and "microstomy" in each scolecophidian lineage. We ultimately emphasize that a rigorous approach to comparative anatomy is necessary in constructing evolutionary hypotheses that accurately reflect biological reality.
Kühne, Franziska ; Fauth, Henriette ; Destina Sevde, Ay-Bryson ; Visser, Leonie N.C. ; Weck, Florian
Background
Communicating a diagnosis is highly important, yet complex, especially in the context of cancer and mental disorders. The aim was to explore the communication style of an oncologist vs. psychotherapist in an online study.
Methods
Patients (N = 136: 65 cancer, 71 depression) were randomly assigned to watch a standardized video vignette with one of two communication styles (empathic vs. unempathic). Outcome measures of affectivity, information recall, communication skills, empathy and trust were applied.
Results
Regardless of diagnosis, empathic communication was associated with the perception of a significantly more empathic (p < 0.001, η2partial = 0.08) and trustworthy practitioner (p = 0.014, η2partial = 0.04) with better communication skills (p = 0.013, η2partial = 0.05). Cancer patients reported a larger decrease in positive affect (p < 0.001, η2partial = 0.15) and a larger increase in negative affect (p < 0.001, η2partial = 0.14) from pre- to post-video than depressive patients. Highly relevant information was recalled better in both groups (p < 0.001, d = 0.61–1.06).
Conclusions
The results highlight the importance of empathy while communicating both a diagnosis of cancer and a mental disorder. Further research should focus on the communication of a mental disorder in association with cancer.
Malchow, Anne-Kathleen ; Bocedi, Greta ; Palmer, Stephen C. F. ; Travis, Justin M. J. ; Zurell, Damaris
Reliably modelling the demographic and distributional responses of a species to environmental changes can be crucial for successful conservation and management planning. Process-based models have the potential to achieve this goal, but so far they remain underused for predictions of species' distributions. Individual-based models offer the additional capability to model inter-individual variation and evolutionary dynamics and thus capture adaptive responses to environmental change. We present RangeShiftR, an R implementation of a flexible individual-based modelling platform which simulates eco-evolutionary dynamics in a spatially explicit way. The package provides flexible and fast simulations by making the software RangeShifter available for the widely used statistical programming platform R. The package features additional auxiliary functions to support model specification and analysis of results. We provide an outline of the package's functionality, describe the underlying model structure with its main components and present a short example. RangeShiftR offers substantial model complexity, especially for the demographic and dispersal processes. It comes with elaborate tutorials and comprehensive documentation to facilitate learning the software and provide help at all levels. As the core code is implemented in C++, the computations are fast. The complete source code is published under a public licence, making adaptations and contributions feasible. The RangeShiftR package facilitates the application of individual-based and mechanistic modelling to eco-evolutionary questions by operating a flexible and powerful simulation model from R. It allows effortless interoperation with existing packages to create streamlined workflows that can include data preparation, integrated model specification and results analysis. Moreover, the implementation in R strengthens the potential for coupling RangeShiftR with other models.
Malchow, Anne-Kathleen ; Bocedi, Greta ; Palmer, Stephen C. F. ; Travis, Justin M. J. ; Zurell, Damaris
Reliably modelling the demographic and distributional responses of a species to environmental changes can be crucial for successful conservation and management planning. Process-based models have the potential to achieve this goal, but so far they remain underused for predictions of species' distributions. Individual-based models offer the additional capability to model inter-individual variation and evolutionary dynamics and thus capture adaptive responses to environmental change. We present RangeShiftR, an R implementation of a flexible individual-based modelling platform which simulates eco-evolutionary dynamics in a spatially explicit way. The package provides flexible and fast simulations by making the software RangeShifter available for the widely used statistical programming platform R. The package features additional auxiliary functions to support model specification and analysis of results. We provide an outline of the package's functionality, describe the underlying model structure with its main components and present a short example. RangeShiftR offers substantial model complexity, especially for the demographic and dispersal processes. It comes with elaborate tutorials and comprehensive documentation to facilitate learning the software and provide help at all levels. As the core code is implemented in C++, the computations are fast. The complete source code is published under a public licence, making adaptations and contributions feasible. The RangeShiftR package facilitates the application of individual-based and mechanistic modelling to eco-evolutionary questions by operating a flexible and powerful simulation model from R. It allows effortless interoperation with existing packages to create streamlined workflows that can include data preparation, integrated model specification and results analysis. Moreover, the implementation in R strengthens the potential for coupling RangeShiftR with other models.