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Institute
Guhn, Anne ; Dresler, Thomas ; Andreatta, Marta ; Müller, Laura D. ; Hahn, Tim ; Tupak, Sara V. ; Polak, Thomas ; Deckert, Jürgen ; Herrmann, Martin J.
The extinction of conditioned fear depends on an efficient interplay between the amygdala and the medial prefrontal cortex (mPFC). In rats, high-frequency electrical mPFC stimulation has been shown to improve extinction by means of a reduction of amygdala activity. However, so far it is unclear whether stimulation of homologues regions in humans might have similar beneficial effects. Healthy volunteers received one session of either active or sham repetitive transcranial magnetic stimulation (rTMS) covering the mPFC while undergoing a 2-day fear conditioning and extinction paradigm. Repetitive TMS was applied offline after fear acquisition in which one of two faces (CS+ but not CS−) was associated with an aversive scream (UCS). Immediate extinction learning (day 1) and extinction recall (day 2) were conducted without UCS delivery. Conditioned responses (CR) were assessed in a multimodal approach using fear-potentiated startle (FPS), skin conductance responses (SCR), functional near-infrared spectroscopy (fNIRS), and self-report scales. Consistent with the hypothesis of a modulated processing of conditioned fear after high-frequency rTMS, the active group showed a reduced CS+/CS− discrimination during extinction learning as evident in FPS as well as in SCR and arousal ratings. FPS responses to CS+ further showed a linear decrement throughout both extinction sessions. This study describes the first experimental approach of influencing conditioned fear by using rTMS and can thus be a basis for future studies investigating a complementation of mPFC stimulation to cognitive behavioral therapy (CBT).
Grozdanov, Veselin D. ; Bousset, Luc ; Hoffmeister, Meike ; Bliederhäuser, Corinna ; Meier, Christoph ; Madiona, Karine ; Pieri, Laura ; Kiechle, Martin ; McLean, Pamela J. ; Kassubek, Jan ; Behrends, Christian ; Ludolph, Albert C. ; Weishaupt, Jochen H. ; Melki, Ronald ; Danzer, Karin
Objective: Excessive inflammation in the central nervous system (CNS) and the periphery can result in neurodegeneration and parkinsonism. Recent evidence suggests that immune responses in Parkinson disease patients are dysregulated, leading to an increased inflammatory reaction to unspecific triggers. Although α‐synuclein pathology is the hallmark of Parkinson disease, it has not been investigated whether pathologic α‐synuclein is a specific trigger for excessive inflammatory responses in Parkinson disease.
Methods: We investigated the immune response of primary human monocytes and a microglial cell line to pathologic forms of α‐synuclein by assessing cytokine release upon exposure.
Results: We show that pathologic α‐synuclein (mutations, aggregation) results in a robust inflammatory activation of human monocytes and microglial BV2 cells. The activation is conformation‐ dependent, with increasing fibrillation and early onset mutations having the strongest effect on immune activation. We also found that activation of immune cells by extracellular α‐synuclein is potentiated by extracellular vesicles, possibly by facilitating the uptake of α‐synuclein. Blood extracellular vesicles from Parkinson disease patients induce a stronger activation of monocytes than blood extracellular vesicles from healthy controls. Most importantly, monocytes from Parkinson disease patients are dysregulated and hyperactive in response to stimulation with pathologic α‐synuclein. Furthermore, we demonstrate that α‐synuclein pathology in the CNS is sufficient to induce the monocyte dysregulation in the periphery of a mouse model.
Interpretation: Taken together, our data suggest that α‐synuclein pathology and dysregulation of monocytes in Parkinson disease can act together to induce excessive inflammatory responses to α‐synuclein. ANN NEUROL 2019;86:593–606
In recent years, many European cities have developed strategies to improve the quality of urban life by reducing car traffic and increasing the attractiveness of alternative modes and the built environment for residents. Frequently, at least in German cities, improvements to the cycling infrastructures play a key role in this transformation of urban spaces. One of those transformative interventions took place in 2020 in Frankfurt am Main (Germany). The city redesigned an arterial road close to the city centre, the Friedberger Landstrasse, by converting two car lanes to bicycle lanes. It is the aim of this study to analyse the effects of this change on the quality of urban life of its residents using a quantitative before-and-after study. The results demonstrate the expected improvements in the perceived quality of urban life for residents after the intervention. A more detailed analysis, however, shows that the residents’ perceptions vary according to their own mode use on the Friedberger Landstrasse and other sociodemographic characteristics. Thus, better cycling infrastructure does not only improve conditions for cyclists, but also contributes to a higher quality of urban life for residents and, therefore, improves the liveability of a city in two ways. We conclude that local transport policies are not only relevant for a modal shift, but also for the quality of urban life and, thus, related urban development strategies.
Tolerizing CTL by sustained hepatic PD-L1 expression provides a new therapy spproach in mouse sepsis
(2019)
Knethen, Andreas von ; Schäfer, Anne ; Kuchler, Laura ; Knape, Tilo ; Christen, Urs ; Hintermann, Edith ; Fißlthaler, Beate ; Schröder, Katrin ; Brandes, Ralf ; Genz, Berit ; Abshagen, Kerstin ; Pützer, Brigitte M. ; Sha, Lisa K. ; Weigert, Andreas ; Syed, Shahzad Nawaz ; Schulz, Martin ; Shah, Ajay M. ; Erns, Andreas ; Putyrski, Mateusz ; Finkelmeier, Fabian ; Pešić, Marina ; Greten, Florian ; Hogardt, Michael ; Kempf, Volkhard A. J. ; Gunne, Sandra ; Parnham, Michael J. ; Brüne, Bernhard
Cytotoxic T lymphocyte (CTL) activation contributes to liver damage during sepsis, but the mechanisms involved are largely unknown. Understanding the underlying principle will permit interference with CTL activation and thus, provide a new therapeutic option.
Methods: To elucidate the mechanism leading to CTL activation we used the Hepa1-6 cell line in vitro and the mouse model of in vivo polymicrobial sepsis, following cecal-ligation and -puncture (CLP) in wildtype, myeloid specific NOX-2, global NOX2 and NOX4 knockout mice, and their survival as a final readout. In this in vivo setting, we also determined hepatic mRNA and protein expression as well as clinical parameters of liver damage - aspartate- and alanine amino-transaminases. Hepatocyte specific overexpression of PD-L1 was achieved in vivo by adenoviral infection and transposon-based gene transfer using hydrodynamic injection.
Results: We observed downregulation of PD-L1 on hepatocytes in the murine sepsis model. Adenoviral and transposon-based gene transfer to restore PD-L1 expression, significantly improved survival and reduced the release of liver damage, as PD-L1 is a co-receptor that negatively regulates T cell function. Similar protection was observed during pharmacological intervention using recombinant PD-L1-Fc. N-acetylcysteine blocked the downregulation of PD-L1 suggesting the involvement of reactive oxygen species. This was confirmed in vivo, as we observed significant upregulation of PD-L1 expression in NOX4 knockout mice, following sham operation, whereas its expression in global as well as myeloid lineage NOX2 knockout mice was comparable to that in the wild type animals. PD-L1 expression remained high following CLP only in total NOX2 knockouts, resulting in significantly reduced release of liver damage markers.
Conclusion: These results suggest that, contrary to common assumption, maintaining PD-L1 expression on hepatocytes improves liver damage and survival of mice during sepsis. We conclude that administering recombinant PD-L1 or inhibiting NOX2 activity might offer a new therapeutic option in sepsis.
Stecher, Melanie ; Schommers, Philipp Frederik ; Kollan, Christian ; Stoll, Matthias ; Kuhlendahl, Frieder ; Stellbrink, Hans‑Jürgen ; Wasmuth, Jan‑Christian ; Stephan, Christoph ; Hamacher, Laura ; Lehmann, Clara ; Boesecke, Christoph ; Bogner, Johannes ; Esser, Stefan ; Fritzsche, Carlos ; Haberl, Annette ; Hofmann, Christian ; Jensen, Björn ; Schwarze‑Zander, Carolynne ; Platten, Martin ; Fätkenheuer, Gerd ; Schmidt, Daniel ; Gunsenheimer-Bartmeyer, Barbara ; Vehreschild, Jörg Janne
Objective: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving.
Methods: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan–Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data.
Results: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59–66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39–0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011–2017), being on a multi-tablet regimen (MTR).
Conclusions: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.
Stecher, Melanie ; Schommers, Philipp Frederik ; Kollan, Christian ; Stoll, Matthias ; Kuhlendahl, Frieder-Johan ; Stellbrink, Hans‑Jürgen ; Wasmuth, Jan‑Christian ; Stephan, Christoph ; Hamacher, Laura ; Lehmann, Clara ; Boesecke, Christoph ; Bogner, Johannes ; Esser, Stefan ; Fritzsche, Carlos ; Haberl, Annette ; Schürmann, Dirk ; Degen, Olaf ; Horst, Heinz August ; Hoffmann, Christian ; Jensen, Björn-Erik Ole ; Schwarze-Zander, Carolynne ; Platten, Martin ; Fätkenheuer, Gerd ; Schmidt, Daniel ; Gunsenheimer-Bartmeyer, Barbara ; Vehreschild, Jörg Janne
Correction to: Infection (2020) 48:723–733 https://doi.org/10.1007/s15010-020-01469-6. The original version of this article unfortunately contained a mistake. In this article the authors Dirk Schürmann at affiliation Charité, University Medicine, Berlin, Olaf Degen at affiliation University Clinic Hamburg Eppendorf, Hamburg and Heinz-August Horst at affiliation University Hospital Schleswig–Holstein, Kiel, Germany were missing from the author list. The original article has been corrected.
Kennedy, Eamonn ; Vadlamani, Shashank ; Lindsey, Hannah M. ; Lei, Pui-Wa ; Jo-Pugh, Mary ; Adamson, Maheen ; Alda, Martin ; Alonso-Lana, Silvia ; Ambrogi, Sonia ; Anderson, Tim J. ; Arango, Celso ; Asarnow, Robert F. ; Avram, Mihai ; Ayesa-Arriola, Rosa ; Babikian, Talin ; Banaj, Nerisa ; Bird, Laura J. ; Borgwardt, Stefan ; Brodtmann, Amy ; Brosch, Katharina ; Caeyenberghs, Karen ; Calhoun, Vince D. ; Chiaravalloti, Nancy D. ; Cifu, David X. ; Crespo-Facorro, Benedicto ; Dalrymple-Alford, John C. ; Dams-O’Connor, Kristen ; Dannlowski, Udo ; Darby, David ; Davenport, Nicholas ; DeLuca, John ; Díaz-Caneja, Covadonga M. ; Disner, Seth G. ; Dobryakova, Ekaterina ; Ehrlich, Stefan ; Esopenko, Carrie ; Ferrarelli, Fabio ; Frank, Lea E. ; Franz, Carol ; Fuentes-Claramonte, Paola ; Genova, Helen ; Giza, Christopher C. ; Goltermann, Janik ; Grotegerd, Dominik ; Gruber, Marius ; Gutiérrez-Zotes, Alfonso ; Ha, Minji ; Haavik, Jan ; Hinkin, Charles ; Hoskinson, Kristen R. ; Hubl, Daniela ; Irimia, Andrei ; Jansen, Andreas ; Kaess, Michael ; Kang, Xiaojian ; Kenney, Kimbra ; Keřková, Barbora ; Khlif, Mohamed Salah ; Kim, Minah ; Kindler, Jochen ; Kircher, Tilo ; Knı́žková, Karolina ; Kolskår, Knut K. ; Krch, Denise ; Kremen, William S. ; Kuhn, Taylor ; Kumari, Veena ; Kwon, Jun Soo ; Langella, Roberto ; Laskowitz, Sarah ; Lee, Jungha ; Lengenfelder, Jean ; Liebel, Spencer W. ; Liou-Johnson, Victoria ; Lippa, Sara M. ; Løvstad, Marianne ; Lundervold, Astri ; Marotta, Cassandra ; Marquardt, Craig A. ; Mattos, Paulo ; Mayeli, Ahmad ; McDonald, Carrie R. ; Meinert, Susanne ; Melzer, Tracy R. ; Merchán Naranjo, Jessica ; Michel, Chantal ; Morey, Rajendra A. ; Mwangi, Benson ; Myall, Daniel J. ; Nenadić, Igor ; Newsome, Mary R. ; Nunes, Abraham ; O’Brien, Terence J. ; Oertel, Viola ; Ollinger, John ; Olsen, Alexander ; Ortiz Garcı́a de la Foz, Victor ; Ozmen, Mustafa ; Pardoe, Heath ; Parent, Marise ; Piras, Fabrizio ; Piras, Federica ; Pomarol-Clotet, Edith ; Repple, Jonathan ; Richard, Geneviève ; Rodriguez, Jonathan ; Rodriguez, Mabel ; Rootes-Murdy, Kelly ; Rowland, Jared ; Ryan, Nicholas P. ; Salvador, Raymond ; Sanders, Anne-Marthe ; Schmidt, André ; Soares, Jair C. ; Spalleta, Gianfranco ; Španiel, Filip ; Stasenko, Alena ; Stein, Frederike ; Straube, Benjamin ; Thames, April ; Thomas-Odenthal, Florian ; Thomopoulos, Sophia I. ; Tone, Erin ; Torres, Ivan ; Troyanskaya, Maya ; Turner, Jessica A. ; Ulrichsen, Kristine M. ; Umpierrez, Guillermo ; Vilella, Elisabet ; Vivash, Lucy ; Walker, William C. ; Werden, Emilio ; Westlye, Lars T. ; Wild, Krista ; Wroblewski, Adrian ; Wu, Mon-Ju ; Wylie, Glenn R. ; Yatham, Lakshmi N. ; Zunta-Soares, Giovana B. ; Thompson, Paul M. ; Tate, David F. ; Hillary, Frank G. ; Dennis, Emily L. ; Wilde, Elisabeth A.
Investigators in the cognitive neurosciences have turned to Big Data to address persistent replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. While there is tremendous potential to advance science through open data sharing, these efforts unveil a host of new questions about how to integrate data arising from distinct sources and instruments. We focus on the most frequently assessed area of cognition - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated raw data from 53 studies from around the world which measured at least one of three distinct verbal learning tasks, totaling N = 10,505 healthy and brain-injured individuals. A mega analysis was conducted using empirical bayes harmonization to isolate and remove site effects, followed by linear models which adjusted for common covariates. After corrections, a continuous item response theory (IRT) model estimated each individual subject’s latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance by 37% while preserving covariate effects. The effects of age, sex, and education on scores were found to be highly consistent across memory tests. IRT methods for equating scores across AVLTs agreed with held-out data of dually-administered tests, and these tools are made available for free online. This work demonstrates that large-scale data sharing and harmonization initiatives can offer opportunities to address reproducibility and integration challenges across the behavioral sciences.
Non-standard errors
(2021)
Menkveld, Albert J. ; Dreber, Anna ; Holzmeister, Felix ; Huber, Jürgen ; Johannesson, Magnus ; Kirchler, Michael ; Razen, Michael ; Weitzel, Utz ; Abad Díaz, David ; Abudy, Menachem ; Adrian, Tobias ; Ait-Sahalia, Yacine ; Akmansoy, Olivier ; Alcock, Jamie ; Alexeev, Vitali ; Aloosh, Arash ; Amato, Livia ; Amaya, Diego ; Angel, James ; Bach, Amadeus ; Baidoo, Edwin ; Bakalli, Gaetan ; Barbon, Andrea ; Bashchenko, Oksana ; Bindra, Parampreet Christopher ; Bjonnes, Geir Hoidal ; Black, Jeff ; Black, Bernard S. ; Bohorquez, Santiago ; Bondarenko, Oleg ; Bos, Charles S. ; Bosch-Rosa, Ciril ; Bouri, Elie ; Brownlees, Christian ; Calamia, Anna ; Cao, Viet Nga ; Capelle-Blancard, Gunther ; Capera, Laura ; Caporin, Massimiliano ; Carrion, Allen ; Caskurlu, Tolga ; Chakrabarty, Bidisha ; Chernov, Mikhail ; Cheung, William M. ; Chincarini, Ludwig Boris ; Chordia, Tarun ; Chow, Sheung Chi ; Clapham, Benjamin ; Colliard, Jean-Edouard ; Comerton-Forde, Carole ; Curran, Edward ; Dao, Thong ; Dare, Wale ; Davies, Ryan J. ; De Blasis, Riccardo ; De Nard, Gianluca ; Declerck, Fany ; Deev, Oleg ; Degryse, Hans ; Deku, Solomon ; Desagre, Christophe ; Dijk, Mathijs van ; Dim, Chukwuma ; Dimpfl, Thomas ; Dong, Yun Jiang ; Drummond, Philip ; Dudda, Tom ; Dumitrescu, Ariadna ; Dyakov, Teodor ; Haubo Dyhrberg, Anne ; Dzieliński, Michał ; Eksi, Asli ; El Kalak, Izidin ; Ellen, Saskia ter ; Eugster, Nicolas ; Evans, Martin D. D. ; Farrell, Michael ; Félez-Viñas, Ester ; Ferrara, Gerardo ; Ferrouhi, El Mehdi ; Flori, Andrea ; Fluharty-Jaidee, Jonathan ; Foley, Sean ; Fong, Kingsley Y. L. ; Foucault, Thierry ; Franus, Tatiana ; Franzoni, Francesco ; Frijns, Bart ; Frömmel, Michael ; Fu, Servanna ; Füllbrunn, Sascha ; Gan, Baoqing ; Gehrig, Thomas ; Gerritsen, Dirk ; Gil-Bazo, Javier ; Glosten, Lawrence R. ; Gomez, Thomas ; Gorbenko, Arseny ; Güçbilmez, Ufuk ; Grammig, Joachim ; Gregoire, Vincent ; Hagströmer, Björn ; Hambuckers, Julien ; Hapnes, Erik ; Harris, Jeffrey H. ; Harris, Lawrence ; Hartmann, Simon ; Hasse, Jean-Baptiste ; Hautsch, Nikolaus ; He, Xuezhong ; Heath, Davidson ; Hediger, Simon ; Hendershott, Terrence ; Hibbert, Ann Marie ; Hjalmarsson, Erik ; Hoelscher, Seth A. ; Hoffmann, Peter ; Holden, Craig W. ; Horenstein, Alex R. ; Huang, Wenqian ; Huang, Da ; Hurlin, Christophe ; Ivashchenko, Alexey ; Iyer, Subramanian Rama ; Jahanshahloo, Hossein ; Jalkh, Naji ; Jones, Charles M. ; Jurkatis, Simon ; Jylha, Petri ; Kaeck, Andreas ; Kaiser, Gabriel ; Karam, Arzé ; Karmaziene, Egle ; Kassner, Bernhard ; Kaustia, Markku ; Kazak, Ekaterina ; Kearney, Fearghal ; Kervel, Vincent van ; Khan, Saad ; Khomyn, Marta ; Klein, Tony ; Klein, Olga ; Klos, Alexander ; Koetter, Michael ; Krahnen, Jan Pieter ; Kolokolov, Aleksey ; Korajczyk, Robert A. ; Kozhan, Roman ; Kwan, Amy ; Lajaunie, Quentin ; Lam, FY Eric C ; Lambert, Marie ; Langlois, Hugues ; Lausen, Jens ; Lauter, Tobias ; Leippold, Markus ; Levin, Vladimir ; Li, Yijie ; Li, Hui ; Liew, Chee Yoong ; Lindner, Thomas ; Linton, Oliver B. ; Liu, Jiacheng ; Liu, Anqi ; Llorente, Guillermo ; Lof, Matthijs ; Lohr, Ariel ; Longstaff, Francis A. ; Lopez-Lira, Alejandro ; Mankad, Shawn ; Mano, Nicola ; Marchal, Alexis ; Martineau, Charles ; Mazzola, Francesco ; Meloso, Debrah ; Mihet, Roxana ; Mohan, Vijay ; Moinas, Sophie ; Moore, David ; Mu, Liangyi ; Muravyev, Dmitriy ; Murphy, Dermot ; Neszveda, Gabor ; Neumeier, Christian ; Nielsson, Ulf ; Nimalendran, Mahendrarajah ; Nolte, Sven ; Norden, Lars L. ; O'Neill, Peter ; Obaid, Khaled ; Ødegaard, Bernt Arne ; Östberg, Per ; Painter, Marcus ; Palan, Stefan ; Palit, Imon ; Park, Andreas ; Pascual, Roberto ; Pasquariello, Paolo ; Pastor, Lubos ; Patel, Vinay ; Patton, Andrew J. ; Pearson, Neil D. ; Pelizzon, Loriana ; Rzeźnik, Aleksandra ; Sanford, Anthony ; Sankaran, Harikumar ; Sarkar, Asani ; Sarno, Lucio ; Scaillet, O. ; Scharnowski, Stefan ; Schenk-Hoppé, Klaus Reiner ; Schertler, Andrea ; Schneider, Michael ; Schroeder, Florian ; Schürhoff, Norman ; Schuster, Philipp ; Schwarz, Marco A. ; Seasholes, Mark S. ; Seeger, Norman ; Shachar, Or ; Shkilko, Andriy ; Shui, Jessica ; Sikic, Mario ; Simion, Giorgia ; Smales, Lee A. ; Söderlind, Paul ; Sojli, Elvira ; Sokolov, Konstantin ; Spokeviciute, Laima ; Stefanova, Denitsa ; Subrahmanyam, Marti G. ; Neusüss, Sebastian ; Szaszi, Barnabas ; Talavera, Oleksandr ; Tang, Yuehua ; Taylor, Nicholas ; Tham, Wing Wah ; Theissen, Erik ; Thimme, Julian ; Tonks, Ian ; Tran, Hai ; Trapin, Luca ; Trolle, Anders B. ; Valente, Giorgio ; Van Ness, Robert A. ; Vasquez, Aurelio ; Verousis, Thanos ; Verwijmeren, Patrick ; Vilhelmsson, Anders ; Vilkov, Grigory ; Vladimirov, Vladimir ; Vogel, Sebastian ; Voigt, Stefan ; Wagner, Wolf ; Walther, Thomas ; Weiss, Patrick ; Wel, Michel van der ; Werner, Ingrid M. ; Westerholm, Joakim ; Westheide, Christian ; Wipplinger, Evert ; Wolf, Michael ; Wolff, Christiaan Cornelis Petrus ; Wolk, Leonard ; Wong, Wing Keung ; Wrampelmeyer, Jan ; Xia, Shuo ; Xiu, Dacheng ; Xu, Ke ; Xu, Caihong ; Yadav, Pradeep ; Yagüe, José ; Yan, Cheng ; Yang, Antti ; Yoo, Woongsun ; Yu, Wenjia ; Yu, Shihao ; Yueshen, Bart Zhou ; Yuferova, Darya ; Zamojski, Marcin ; Zareei, Abalfazl ; Zeisberger, Stefan ; Zhang, Sarah ; Zhang, Xiaoyu ; Zhong, Zhuo ; Zhou, Z. Ivy ; Zhou, Chen ; Zhu, Xingyu Sonya ; Zoican, Marius ; Zwinkels, Remco C. J. ; Chen, Jian ; Duevski, Teodor ; Gao, Ge ; Gemayel, Roland ; Gilder, Dudley ; Kuhle, Paul ; Pagnotta, Emiliano ; Pelli, Michele ; Sönksen, Jantje ; Zhang, Lu ; Ilczuk, Konrad ; Bogoev, Dimitar ; Qian, Ya ; Wika, Hans C. ; Yu, Yihe ; Zhao, Lu ; Mi, Michael ; Bao, Li ; Vaduva, Andreea ; Prokopczuk, Marcel ; Avetikian, Alejandro ; Wu, Zhen-Xing
In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in sample estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: non-standard errors. To study them, we let 164 teams test six hypotheses on the same sample. We find that non-standard errors are sizeable, on par with standard errors. Their size (i) co-varies only weakly with team merits, reproducibility, or peer rating, (ii) declines significantly after peer-feedback, and (iii) is underestimated by participants.