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1. Overview: quasi-Lagrangian observations of Arctic air mass transformations – introduction and initial results of the HALO–(𝒜 𝒞)3 aircraft campaign

Author: M. Wendisch, S. Crewell, A. Ehrlich, A. Herber, B. Kirbus, C. Lüpkes, M. Mech, S. J. Abel, E. F. Akansu, F. Ament, C. Aubry, S. Becker, S. Borrmann, H. Bozem, M. Brückner, H.-C. Clemen, S. Dahlke, G. Dekoutsidis, J. Delanoë, E. De La Torre Castro, H. Dorff, R. Dupuy, O. Eppers, F. Ewald, G. George, I. V. Gorodetskaya, S. Grawe, S. Groß, J. Hartmann, S. Henning, L. Hirsch, E. Jäkel, P. Joppe, O. Jourdan, Z. Jurányi, M. Karalis, M. Kellermann, M. Klingebiel, M. Lonardi, J. Lucke, A. E. Luebke, M. Maahn, N. Maherndl, M. Maturilli, B. Mayer, J. Mayer, S. Mertes, J. Michaelis, M. Michalkov, G. Mioche, M. Moser, H. Müller, R. Neggers, D. Ori, D. Paul, F. M. Paulus, C. Pilz, F. Pithan, M. Pöhlker, V. Pörtge, M. Ringel, N. Risse, G. C. Roberts, S. Rosenburg, J. Röttenbacher, J. Rückert, M. Schäfer, J. Schaefer, V. Schemann, I. Schirmacher, J. Schmidt, S. Schmidt, J. Schneider, S. Schnitt, A. Schwarz, H. Siebert, H. Sodemann, T. Sperzel, G. Spreen, B. Stevens, F. Stratmann, G. Svensson, C. Tatzelt, T. Tuch, T. Vihma, C. Voigt, L. Volkmer, A. Walbröl, A. Weber, B. Wehner, B. Wetzel, M. Wirth, and T. Zinner
Subjects: Physics, QC1-999, Chemistry, QD1-999
Abstract: Global warming is amplified in the Arctic. However, numerical models struggle to represent key processes that determine Arctic weather and climate. To collect data that help to constrain the models, the HALO–(𝒜𝒞)3 aircraft campaign was conducted over the Norwegian and Greenland seas, the Fram Strait, and the central Arctic Ocean in March and April 2022. The campaign focused on one specific challenge posed by the models, namely the reasonable representation of transformations of air masses during their meridional transport into and out of the Arctic via northward moist- and warm-air intrusions (WAIs) and southward marine cold-air outbreaks (CAOs). Observations were made over areas of open ocean, the marginal sea ice zone, and the central Arctic sea ice. Two low-flying and one long-range, high-altitude research aircraft were flown in colocated formation whenever possible. To follow the air mass transformations, a quasi-Lagrangian flight strategy using trajectory calculations was realized, enabling us to sample the same moving-air parcels twice along their trajectories. Seven distinct WAI and 12 CAO cases were probed. From the quasi-Lagrangian measurements, we have quantified the diabatic heating/cooling and moistening/drying of the transported air masses. During CAOs, maximum values of 3 K h−1 warming and 0.3 g kg−1 h−1 moistening were obtained below 1 km altitude. From the observations of WAIs, diabatic cooling rates of up to 0.4 K h−1 and a moisture loss of up to 0.1 g kg−1 h−1 from the ground to about 5.5 km altitude were derived. Furthermore, the development of cloud macrophysical (cloud-top height and horizontal cloud cover) and microphysical (liquid water path, precipitation, and ice index) properties along the southward pathways of the air masses were documented during CAOs, and the moisture budget during a specific WAI event was estimated. In addition, we discuss the statistical frequency of occurrence of the different thermodynamic phases of Arctic low-level clouds, the interaction of Arctic cirrus clouds with sea ice and water vapor, and the characteristics of microphysical and chemical properties of Arctic aerosol particles. Finally, we provide a proof of concept to measure mesoscale divergence and subsidence in the Arctic using data from dropsondes released during the flights.
Published: 2024
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2. Next-generation ice-nucleating particle sampling on board aircraft: characterization of the High-volume flow aERosol particle filter sAmpler (HERA)

Author: S. Grawe, C. Jentzsch, J. Schaefer, H. Wex, S. Mertes, and F. Stratmann
Subjects: Environmental engineering, TA170-171, Earthwork. Foundations, TA715-787
Abstract: Atmospheric ice-nucleating particle (INP) concentration data from the free troposphere are sparse but urgently needed to understand vertical transport processes of INPs and their influence on cloud formation and properties. Here, we introduce the new High-volume flow aERosol particle filter sAmpler (HERA) which was specially developed for installation on research aircraft and subsequent offline INP analysis. HERA is a modular system consisting of a sampling unit and a powerful pump unit, and it has several features which were integrated specifically for INP sampling. Firstly, the pump unit enables sampling at flow rates exceeding 100 L min−1, which is well above typical flow rates of aircraft INP sampling systems described in the literature (∼ 10 L min−1). Consequently, required sampling times to capture rare, high-temperature INPs (≥ −15 ∘C) are reduced in comparison to other systems, and potential source regions of INPs can be confined more precisely. Secondly, the sampling unit is designed as a seven-way valve, enabling switching between six filter holders and a bypass with one filter being sampled at a time. In contrast to other aircraft INP sampling systems, the valve position is remote-controlled via software so that manual filter changes during flight are eliminated and the potential for sample contamination is decreased. This design is compatible with a high degree of automation, i.e., triggering filter changes depending on parameters like flight altitude, geographical location, temperature, or time. In addition to presenting the design and principle of operation of HERA, this paper describes laboratory characterization experiments with size-selected test substances, i.e., SNOMAX® and Arizona Test Dust. The particles were sampled on filters with HERA, varying either particle diameter (300 to 800 nm) or flow rate (10 to 100 L min−1) between experiments. The subsequent offline INP analysis showed good agreement with literature data and comparable sampling efficiencies for all investigated particle sizes and flow rates. Furthermore, the collection efficiency of atmospheric INPs in HERA was compared to a straightforward filter sampler and good agreement was found. Finally, results from the first campaign of HERA on the High Altitude and LOng range research aircraft (HALO) demonstrate the functionality of the new system in the context of aircraft application.
Published: 2023
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3. Novel ELISA Based on Purified and Recombinant Antigens from Toxocara Canis Exhibits a High Diagnostic Sensitivity

Author: J. Schaefer, B. Menge, K. Stiba, J. Dibbern, V. Borchardt-Lohölter, K. Steinhagen, and W. Schlumberger
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: Purpose: Toxocariasis is a zoonosis that is mainly caused by the dog roundworm Toxocara canis and the cat roundworm T. cati. The prevalence of T. canis-specific antibodies in humans is 2-5% in Germany. Many infections with Toxocara spp. have a subclinical course, but can develop into a severe disease, with visceral, ocular, or neurotoxic manifestations. While first serological antibody detection methods were based on the whole lysate from T. canis larvae, meanwhile Toxocara excretory/secretory (TES) antigens from larvae cultures are used. Here, we evaluated the diagnostic performance of a new ELISA based on a highly purified larval antigen from T. canis and recombinant TES antigen. Methods & Materials: [1] Comparison with an external quality assessment scheme (NEQAS, UK) encompassing 9 positive and 8 negative sera.[2] Agreement study with a commercial Toxocara canis IgG ELISA (based on T. canis antigens; IBL International, Germany) including 117 sera pre-characterised by IBL ELISA.[3] Specificity was evaluated with respect to a control panel containing 586 sera from healthy blood donors, 98 from pregnant women and 197 from children as well as a cross-reactivity panel (135 sera from patients infected with Strongyloides, Schistosoma, Ascaris, Trichinella and other parasitic/bacterial infections). Results: Results obtained with the Anti-Toxocara ELISA were 100% in agreement with the NEQAS target values (sensitivity: 88.9%, specificity: 100%).The agreement between the two methods was substantial (79%, κ=0.57). The EUROIMMUN ELISA found 86 and the IBL ELISA 71 positive samples (negative predictive value=1). The EUROIMMUN ELISA found 23 and the IBL ELISA 41 negative samples. Thirteen discrepant samples were positive in the EUROIMMUN ELISA but negative in the IBL ELISA.The Anti-Toxocara ELISA was reactive in 25.9% of samples in the cross-reactivity panel and in 4.5% of the samples from healthy individuals, yielding a combined specificity of 92.6%. Conclusion: The novel Anti-Toxocara ELISA is a valuable screening test for sensitive serological detection of T. canis infections. Possible past infections or double infections with other parasites should be considered when evaluating the test result. A positive ELISA test result could be confirmed by a corresponding Western blot, which is available from EUROIMMUN.
Published: 2022
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4. Validated low-volume aldosterone immunoassay tailored to GCLP-compliant investigations in small sample volumes

Author: J. Schaefer, B.B. Burckhardt, J. Tins, A. Bartel, and S. Laeer
Subjects: Medicine (General), R5-920, Chemistry, QD1-999
Abstract: Introduction: Heart failure is well investigated in adults, but data in children is lacking. To overcome this shortage of reliable data, appropriate bioanalytical assays are required. Objectives: Development and validation of a bioanalytical assay for the determination of aldosterone concentrations in small sample volumes applicable to clinical studies under Good Clinical Laboratory Practice. Methods: An immunoassay was developed based on a commercially available enzyme-linked immunosorbent assay and validated according to current bioanalytical guidelines of the European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA). Results: The assay (range 31.3–1000 pg/mL [86.9–2775 pmol/L]) is characterized by a between-run accuracy from − 3.8% to − 0.8% and a between-run imprecision ranging from 4.9% to 8.9% (coefficient of variation). For within-run accuracy, the relative error was between − 11.1% and + 9.0%, while within-run imprecision ranged from 1.2% to 11.8% (CV). For parallelism and dilutional linearity, the relative error of back-calculated concentrations varied from − 14.1% to + 8.4% and from − 7.4% to + 10.5%, respectively. Conclusions: The immunoassay is compliant with the bioanalytical guidelines of the EMA and FDA and allows accurate and precise aldosterone determinations. As the assay can run low-volume samples of 40 μL, it is especially valuable for pediatric investigations. Keywords: Aldosterone, Immunoassay, Pediatric, Pharmacodynamic, Validation, Low-volume
Published: 2017
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5. Population dynamics with symmetric and asymmetric harvesting

Author: Jaffar Ali, D. Perry, S. Sasi, J. Schaefer, B. Schilling, Ratnasingham Shivaji, and M. Williams
Subjects: Mathematics, QA1-939
Abstract: We study the positive solutions to steady state reaction diffusion equations with Dirichlet boundary conditions of the forms: \begin{align} -u''&=\left\{\begin{array}{ll} \lambda[au-bu^{2}-c], & x\in(L,1-L),\\ \lambda[au-bu^{2}], & x\in(0,L)\cup(1-L,1), \end{array} \right.\tag{A}\\ u(0)&=0 =u(1),\nonumber \end{align} and \begin{align} -u''&=\left\{\begin{array}{ll} \lambda[au-bu^{2}-c], & x\in(0,\frac{1}{2}),\\ \lambda[au-bu^{2}], & x\in(\frac{1}{2},1), \end{array} \right.\tag{B}\\ u(0)&=0 =u(1).\nonumber \end{align} Here $\lambda, a, b, c$ and $L$ are positive constants with $0
Published: 2009
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6. Near field computation of the extinction of electromagnetic waves in multiparticle systems

Author: J. Schaefer and A. Kienle
Subjects: Science (General), Q1-390
Abstract: In this contribution extinction of electromagnetic waves inside a medium consisting of cylindrical absorbing particles is considered. Near fields are calculated using a numerical solution of Maxwell’s equations and compared to results given by Lambert- Beer’s law.
Published: 2011
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7. The Role of Formal Policy to Promote Informed Consent of Psychotropic Medications for Youth in Child Welfare Custody: A National Examination

Author: Thomas I. Mackie, Ana J. Schaefer, John S. Palatucci, Laurel K. Leslie, Stephen Crystal, Michael Gusmano, and Hannah E. Karpman
Abstract: Active participation of youth and surrogate decision-makers in providing informed consent and assent for mental health treatment is critical. However, the procedural elements of an informed consent process, particularly for youth in child welfare custody, are not well defined. Given calls for psychotropic medication oversight for youth in child welfare custody, this study proposes a taxonomy for the procedural elements of informed consent policies based upon formal and informal child welfare policies and then examines whether enacted state formal policies across the United States endorsed these elements. A sequential multi-method study design included: (1) semi-structured interviews with key informants (n = 58) primarily from state child welfare agencies to identify a taxonomy of procedural elements for informed consent of psychotropic medications and then (2) a legislative review of the 50 states and D.C. to characterize whether formal policies endorsed each procedural element through February 2022. Key informants reported five procedural elements in policy, including how to: (1) gather social and medical history, (2) prescribe the medication, (3) authorize its use through consent and youth assent, (4) notify relevant stakeholders, and (5) routinely review the consenting decision. Twenty-three states endorsed relevant legislation; however, only two states specified all five procedural elements. Additionally, the content of a procedural element, when included, varied substantively across policies. Further research and expert consensus are needed to set best practices and guide policymakers in setting policies to advance transparency and accountability for informed consent of mental health treatment among youth in child welfare custody.
Published: 2022
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8. Analysis of a Statewide Early Intervention Program for Young Children with ASD

Author: Myers, Aaron J., Cleveland, Elizabeth, Whitby, Peggy J. Schaefer, Boykin, Allison Ames, Burnette, Karan, Holmes, Renee, and Ezike, Nnamdi
Abstract: We evaluated the effectiveness of a statewide Medicaid program providing in-home Early Intensive Behavioral Intervention services to young children with Autism Spectrum Disorder living in a rural southern state. Program effectiveness was assessed via the Assessment of Basic Language and Learning Skills-Revised (ABLLS-R). A multi-level growth model was used to show significant variation among children's initial ABLLS-R scores and their growth trajectories. Hispanic children tended to have lower initial scores but demonstrated similar growth compared to their non-Hispanic peers. Children who were older at initial start in the program appeared to have higher initial composite scores and higher growth trajectories. Children in more populous counties had higher initial scores but grew at similar rates to children in more rural counties.
Published: 2022
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9. Intake, digestibility and passage rate of a supplemented hay diet in captive muskoxen

Author: J. Adamczewski, R. Chaplin, J. Schaefer, and P. F. Flood
Subjects: muskoxen, supplemented hay, supplementary feeding, Animal culture, SF1-1100
Published: 1993
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10. Parent Implementation of Structured Work Systems on Child Acquisition of Independence Skills through Family Preferred Routines

Author: Kucharczyk, Suzanne, Whitby, Peggy J. Schaefer, and Mrla, Tiffany
Abstract: Evidence-based practices have been identified for children with autism spectrum disorder (ASD). Given the co-occurrence of ASD and visual impairments (VI), it is critical that the effectiveness of these practices be assessed with children who have ASD and VI. Structured work systems have not been evaluated for children with ASD and VI. Structured work systems have been identified as evidence-based practices for children and youth with ASD under the category of visual supports. Additionally, while parent-implemented interventions have proven effective for children with multiple disabilities, parent-implemented interventions are most often researched with young children with insufficient focus on maintenance and generalization. Using a multiple baseline across routines, this study assesses the effectiveness of structured work systems implemented by a parent on independence in skills for a child with ASD and VI. Parent-implemented structured work system were effective across three routines, maintained at 1, 2, and 3 weeks post treatment, and generalized to another parent and new materials.
Published: 2019

11. Parental stress, family quality of life, and family-teacher partnerships: Families of children with autism spectrum disorder

Author: Hsiao, Yun-Ju, Higgins, Kyle, Pierce, Tom, Whitby, Peggy J. Schaefer, and Tandy, Richard D.
Published: 2017
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12. The ChatGPT Artificial Intelligence Chatbot: How Well Does It Answer Accounting Assessment Questions?

Author: David A. Wood, Muskan P. Achhpilia, Mollie T. Adams, Sanaz Aghazadeh, Kazeem Akinyele, Mfon Akpan, Kristian D. Allee, Abigail M. Allen, Elizabeth D. Almer, Daniel Ames, Viktor Arity, Dereck Barr-Pulliam, K. Asli Basoglu, Andrew Belnap, Jeremiah W. Bentley, Terje Berg, Nathan R. Berglund, Erica Berry, Avishek Bhandari, Md Nazmul Hasan Bhuyan, Paul W. Black, Eva Blondeel, David Bond, Annika Bonrath, A. Faye Borthick, Erik S. Boyle, Marianne Bradford, Duane M. Brandon, Joseph F. Brazel, Bryan G. Brockbank, Marcus Burger, Dmitri Byzalov, James N. Cannon, Cecil Caro, Abraham H. Carr, Jack Cathey, Ryan Cating, Kimberly Charron, Stacy Chavez, Jason Chen, Jennifer C. Chen, Jennifer W. Chen, Christine Cheng, Xu Cheng, Brant E. Christensen, Kimberly Swanson Church, N. J. Cicone, Patience Constance, Lauren A. Cooper, Candice L. Correia, Joshua Coyne, W. Alec Cram, Asher Curtis, Ronald J. Daigle, Steve Dannemiller, Stephan A. Davenport, Gregory S. Dawson, Karen J. L. De Meyst, Scott Dell, Sebahattin Demirkan, Christine A. Denison, Hrishikesh Desai, Steven DeSimone, Leah M. Diehl, Ruth Dimes, Bei Dong, Amy Donnelly, Adam du Pon, Huijue Kelly Duan, Ada Duffey, Ryan T. Dunn, Mary P. Durkin, Ann C. Dzuranin, Rachel M. Eberle, Matthew S. Ege, Dina El Mahdy, Adam Esplin, Marc Eulerich, Patricia Everaert, Nusrat Farah, Lauren Farish, Michael Favere-Marchesi, Dutch Fayard, Jessica R. Filosa, Melinda Ford, Diana R. Franz, Bachman P. Fulmer, Sarah Fulmer, Zhan Z. Furner, Sonia Gantman, Steve Garner, Jace Garrett, Xin Geng, Joanna Golden, William Goldman, Josue Gomez, Mark Gooley, Shawn P. Granitto, Karen Y. Green, Cindy L. Greenman, Gaurav Gupta, Ronald N. Guymon, Kevin Hale, Christopher J. Harper, S. Allen Hartt, Holly Hawk, Steven R. Hawkins, Erin M. Hawkins, David C. Hay, Rafael Heinzelmann, Cassy D. Henderson, Bradley E. Hendricks, William G. Heninger, Mary S. Hill, Nicole Holden, D. Kip Holderness, Travis P. Holt, Jeffrey L. Hoopes, Sheng-Feng Hsieh, Feiqi Huang, Hua-Wei Huang, Ting-Chiao Huang, Brian W. Huels, Kara Hunter, Patrick J. Hurley, Kerry Inger, Sharif Islam, Isaac Ison, Hussein Issa, Andrew B. Jackson, Scott C. Jackson, Diane J. Janvrin, Peggy D. Jimenez, Daniel Johanson, J. Scott Judd, Brett S. Kawada, Andrea Seaton Kelton, Sara Kern, Jon N. Kerr, Marsha B. Keune, Mindy Kim, Brian D. Knox, Gregory Kogan, Amr Kotb, Ronja Krane, Joleen Kremin, Kimberly S. Krieg, Jonathan Kugel, Ellen M. Kulset, Chamara Kuruppu, Garrison LaDuca, Barbara A. Lamberton, Melvin A. Lamboy-Ruiz, Bradley Lang, Stephannie A. Larocque, Melissa P. Larson, Bradley P. Lawson, James G. Lawson, Lorraine Lee, Margarita M. Lenk, Michelle Li-Kuehne, Jonathan Liljegren, Yi-Hung Lin, Wu-Po Liu, Zishang Liu, Brandon Lock, James H. Long, Tina Loraas, Suzanne Lowensohn, Thomas R. Loy, Hakim Lyngstadaas, Wim Maas, Jason E. MacGregor, Dag Øivind Madsen, Carissa L. Malone, Maximilian Margolin, Mary E. Marshall, Rachel M. Martin, Colleen McClain Mpofu, Chris McCoy, Nicholas C. McGuigan, Dwayne N. McSwain, Michele D. Meckfessel, Mark J. Mellon, Olivia S. Melton, Julie M. Mercado, Steven Mitsuda, Kennedy Modugu, Stephen Moehrle, Amirali Moeini Chaghervand, Kevin Moffitt, Joon Seok Moon, Brigitte Muehlmann, Johnna Murray, Emmanuel S. Mwaungulu, Noah Myers, J. Conrad Naegle, Martin J. Ndicu, Aaron S. Nelson, Anh L. Nguyen, Thomas Niederkofler, Ehsan Nikbakht, Ann D. O'Brien, Kehinde M. Ogunade, Daniel O'Leary, Mitchell J. Oler, Derek K. Oler, Kari Joseph Olsen, John I. Otalor, Kyle W. Outlaw, Michael. E. Ozlanski, Jenny Parlier, Jeffrey S. Paterson, Christopher A. Pearson, Michael J. Petersen, Steven T. Petra, Matthew D. Pickard, Jeffrey Pickerd, Robert Pinsker, Catherine Plante, James M. Plečnik, Richard A. Price, Linda A. Quick, Jana Raedy, Robyn Raschke, Julie Ravenscraft, Vernon Richardson, Brett A. Rixom, John F. Robertson, Iyad Rock, Miles A. Romney, Andrea Rozario, Michael F. Ruff, Kathleen Rupley, Ali Saeedi, Aaron Saiewitz, Leigh W. Salzsieder, Sayan Sarkar, Michael Saulls, Tialei A. Scanlan, Tammie J. Schaefer, Daniel Schaupp, Gary P. Schneider, Andreas Seebeck, R. Drew Sellers, Samantha C. Seto, Romi-Lee Sevel, Yuxin Shan, Matthew G. Sherwood, Maggie Singorahardjo, Hanna Kristin Skaftadottir, Justyna Skomra, Jason L. Smith, Dallin O. Smith, James Smith, Mason C. Snow, Ryan D. Sommerfeldt, Kate B. Sorensen, Trevor L. Sorensen, Andrew C. Spieler, Matthew A. Stallings, Lesya Stallings, Alan Stancill, Jonathan D. Stanley, Chad M. Stefaniak, Nathaniel M. Stephens, Bryan W. Stewart, Theophanis C. Stratopoulos, Daniel A. Street, Meena Subedi, Scott L. Summers, Charlotte H. Sundkvist, Christina Synn, Amanuel Tadesse, Gregory P. Tapis, Kerri Tassin, Samantha Taylor, Mary Teal, Ryan Teeter, Meredith Tharapos, Jochen C. Theis, Jack Thomas, Kristen S. Thompson, Todd A. Thornock, Wendy Tietz, Anthony M. Travalent, Brad S. Trinkle, J. Mike Truelson, Michael C. Turner, Brandon Vagner, Hamid Vakilzadeh, Jesse van der Geest, Victor van Pelt, Scott D. Vandervelde, Jose Vega, Sandra Vera-Muñoz, Brigham Villanueva, Nishani Edirisinghe Vincent, Martin Wagener, Stephanie Walton, Rick C. Warne, Olena V. Watanabe, David Watson, Marcia Weidenmier Watson, Jill Weber, Thomas Weirich, Ashley N. West, Amanda L. Wilford, Aaron B. Wilson, Brian Winrow, Timothy Winrow, Tasia S. Winrow, Denise Wiseman, Annie L. Witte, Bryan D. Wood, Jessica Wood, Darryl Woolley, Nicole S. Wright, Juan Wu, Xiaomei Xiong, Dimitri Yatsenko, Courtney E. Yazzie, Glen M. Young, Chanyuan Zhang, Aleksandra B. Zimmerman, Emily Zoet, Department of Accounting & Control, and Accounting Group
Subjects: Accounting, Education
Abstract: ChatGPT, a language-learning model chatbot, has garnered considerable attention for its ability to respond to users’ questions. Using data from 14 countries and 186 institutions, we compare ChatGPT and student performance for 28,085 questions from accounting assessments and textbook test banks. As of January 2023, ChatGPT provides correct answers for 56.5 percent of questions and partially correct answers for an additional 9.4 percent of questions. When considering point values for questions, students significantly outperform ChatGPT with a 76.7 percent average on assessments compared to 47.5 percent for ChatGPT if no partial credit is awarded and 56.5 percent if partial credit is awarded. Still, ChatGPT performs better than the student average for 15.8 percent of assessments when we include partial credit. We provide evidence of how ChatGPT performs on different question types, accounting topics, class levels, open/closed assessments, and test bank questions. We also discuss implications for accounting education and research.
Published: 2023

13. Acceptance of Chinese latecomers' technological contributions in international ICT standardization — the role of origin, experience and collaboration

Author: Lennart Schott and Kerstin J. Schaefer
Subjects: China, Strategy and Management, Latecomers, Management Science and Operations Research, Dewey Decimal Classification::600 | Technik, Standardization, Standardization capabilities, HD Industries. Land use. Labor, Dewey Decimal Classification::300 | Sozialwissenschaften, Soziologie, Anthropologie::330 | Wirtschaft, Management of Technology and Innovation, ICT, ddc:330, 3GPP, ddc:500, ddc:600, Dewey Decimal Classification::500 | Naturwissenschaften
Abstract: As technical standards are an important part of China's industrial transformation towards an innovation-driven economy, Chinese organizations have started to deploy substantial resources in recent years to take on a leading role in international ICT standardization. However, many Chinese organizations experience, similar to other latecomers to standardization, limited success when contributing to standardization processes, a phenomenon also referred to as the standardization gap. The literature on standardization to date has paid little attention to how Chinese latecomers enter and influence international standardization processes that have traditionally been shaped by organizations from industrialized countries. We therefore analyze the country-of-origin effect as well as factors such as experience and collaboration for successful contributions of Chinese organizations to standards. Using data from the Third Generation Partnership Project (3GPP) and binary logistic regression analysis, we are able to show that, in our sample, contributions from Chinese latecomers are significantly less likely to be accepted than those from more established actors from industrialized economies. Moreover, our findings indicate that experience is closely associated with success in international ICT standardization, but not moderated by national origin. Therefore, Chinese latecomers might not be able to catch up if they move at the same pace as established competitors. They need to find a way to leapfrog extensive development steps, narrow the standardization capability gap, and thus strengthen their participation and influence. One way to do so might be through strategic collaboration, as our results suggest that Chinese organizations benefit more from collaborating with organizations from more established regions than vice versa, on which we call for further research to establish the causal mechanisms.
Published: 2023

14. Rapid-cycle systems modeling to support evidence-informed decision-making during system-wide implementation

Author: Thomas I. Mackie, Ana J. Schaefer, Gracelyn Cruden, and R. Christopher Sheldrick
Subjects: Medicine (General), Evidence-based practice, Process management, Computer science, Process (engineering), Simulation modeling, Stakeholder, Methodology, Stakeholder engagement, General Medicine, Epistemology, Systems modeling, Computer simulation, R5-920, Psychological trauma, Screening, Relevance (law), Implementation science, Qualitative research
Abstract: BackgroundTo “model and simulate change” is an accepted strategy to support implementation at scale. Much like a power analysis can inform decisions about study design, simulation models offer ananalytic strategyto synthesize evidence that informs decisions regarding implementation of evidence-based interventions. However, simulation modeling is under-utilized in implementation science. To realize the potential of simulation modeling as animplementation strategy, additional methods are required to assist stakeholders to use models to examine underlying assumptions, consider alternative strategies, and anticipate downstream consequences of implementation. To this end, we propose Rapid-cycle Systems Modeling (RCSM)—a form of group modeling designed to promote engagement with evidence to support implementation. To demonstrate its utility, we provide an illustrative case study with mid-level administrators developing system-wide interventions that aim to identify and treat trauma among children entering foster care.MethodsRCSM is an iterative method that includes three steps per cycle: (1) identify and prioritize stakeholder questions, (2) develop or refine a simulation model, and (3) engage in dialogue regarding model relevance, insights, and utility for implementation. For the case study, 31 key informants were engaged in step 1, a prior simulation model was adapted for step 2, and six member-checking group interviews (n= 16) were conducted for step 3.ResultsStep 1 engaged qualitative methods to identify and prioritize stakeholder questions, specifically identifying a set of inter-related decisions to promote implementing trauma-informed screening. In step 2, the research team created a presentation to communicate key findings from the simulation model that addressed decisions about programmatic reach, optimal screening thresholds to balance demand for treatment with supply, capacity to start-up and sustain screening, and availability of downstream capacity to provide treatment for those with indicated need. In step 3, member-checking group interviews with stakeholders documented the relevance of the model results to implementation decisions, insight regarding opportunities to improve system performance, and potential to inform conversations regarding anticipated implications of implementation choices.ConclusionsBy embedding simulation modeling in a process of stakeholder engagement, RCSM offers guidance to realize the potential of modeling not only as an analytic strategy, but also as an implementation strategy.
Published: 2021

15. The Effects of 'Solve It!' on the Mathematical Word Problem Solving Ability of Adolescents with Autism Spectrum Disorders

Author: Whitby, Peggy J. Schaefer
Abstract: General education placement of students with autism spectrum disorders (ASD) has increased at a rate faster than all other disability categories combined. As more children are diagnosed with ASD and expected to meet the same academic standards as their neurotypical peers, there is a demand for effective educational strategies. Using a multiple-baseline across participants design, seven cognitive strategies and three meta-cognitive strategies from the "Solve it!" Problem Solving Routine were taught to three adolescents with ASD. Percent of correct responses on word problems improved immediately upon implementation of the intervention. A peer comparison validation strategy was used to compare participants' accuracy with the class average. All three participants got more problems correct during intervention when compared with their peers; this effect persisted for two participants during maintenance. The impact of the characteristics of ASD on the use of each strategy implemented within the "Solve It!" Problem Solving Routine is discussed. (Contains 3 tables and 1 figure.)
Published: 2013
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16. Academic Achievement Profiles of Children with High Functioning Autism and Asperger Syndrome: A Review of the Literature

Author: Whitby, Peggy J. Schaefer and Mancil, G. Richmond
Abstract: High functioning autism (HFA) and Asperger syndrome (AS) are foremost social disorders (Church, Alisanski, & Amanullah, 2000; Myles & Simpson, 2001) yet many students with HFA/AS experience difficulties with academic functioning. Educators report difficulties in teaching and identifying appropriate educational interventions for children with HFA/AS. Research in the area of academic achievement of children with HFA/AS is in the stage of infancy and more research is needed (Prior, 2003). To address the need for development of appropriate academic interventions, several research studies have been conducted to determine the academic achievement profile of children with AS/ HFA (Barnhill, Hagiwara, Smith Myles, & Simpson, 2000; Dickerson Mayes & Calhoun, 2003a, 2003b, 2008; Goldstein, Minshew, & Siegel, 1994; Griswold, Barnhill, Smith Myles, Hagiwara, & Simpson, 2002; Minshew, Goldstein, Taylor, & Siegel, 1994). This article provides a synthesis of the literature on the academic achievement of students with HFA/AS from 1981 to the present to help determine if an academic profile for students with HFA/AS emerges. (Contains 3 tables.)
Published: 2009

17. Academic Achievement and Strategy Instruction to Support the Learning of Children with High-Functioning Autism

Author: Whitby, Peggy J. Schaefer, Travers, Jason C., and Harnik, Jamie
Abstract: Autism is one of the fastest developing childhood disorders. The increase in the prevalence of autism spectrum disorders (ASD) has been highlighted in the media once again. The prevalence of school-age children with ASD has a considerable impact on the schools and teachers who are responsible for their education. Children with ASD served in the general education setting are likely to be those with high-functioning autism or Asperger syndrome (HFA/AS). In a review of the literature on the academic profile of students with HFA/AS, Whitby and Mancil (in press) found consistent academic achievement patterns across research studies, suggesting an academic profile. This article presents the findings on the review of the literitare in reading, writing, and mathematics. It describes strategy instruction as an effective academic intervention for children with learning disabilities, and discusses current research on strategy use and strategy instruction for students with HFA/AS. Anaphoric cueing for reading strategy instruction, self-regulation strategy development for writing, and "Solve It!" Problem Solving Routine for mathematics are presented. (Contains 5 tables.)
Published: 2009

18. Federal Policy and the Education of Students with Disabilities: Progress and the Path Forward

Author: West, Jane E. and Whitby, Peggy J. Schaefer
Abstract: Federal policy has had a significant effect on the education of students with disabilities in the United States. From the Supreme Court cases of the 1970s to the No Child Left Behind Act (NCLB) accountability provisions of the early 21st Century, students with disabilities, their families, and educators who work with them have been mightily shaped by the force of federal policy. While surely there are well documented unintended consequences--under-resourced requirements, unenforced mandates, and examples of poor implementation--there have also been significant milestones of progress. This article provides a 500,000 foot overview of some of the progress to date and some of the opportunities on the horizon. It presents evidenced-based outcomes of NCLB for students with disabilities and considers the path forward as the authors approach reauthorization of NCLB. The authors consider three specific areas of gains under NCLB for students with disabilities: (1) awareness; (2) access; and (3) achievement. (Contains 6 figures.)
Published: 2008

19. The decision sampling framework: a methodological approach to investigate evidence use in policy and programmatic innovation

Author: Thomas I. Mackie, Justeen Hyde, Laurel K. Leslie, R. Christopher Sheldrick, Emily Adlin Bosk, Ana J. Schaefer, and Brittany Fishman
Subjects: Decision sciences, Knowledge management, Health Informatics, Health informatics, Health administration, 03 medical and health sciences, 0302 clinical medicine, Health care policy, Humans, Medicine, 030212 general & internal medicine, Child, Foster care, Qualitative Research, Health policy, Evidence, lcsh:R5-920, Public Sector, business.industry, 030503 health policy & services, Health Policy, Specific-information, Public sector, Mental health care policy, Administrative Personnel, Methodology, Public Health, Environmental and Occupational Health, Health services research, General Medicine, Policy, Research Design, 0305 other medical science, business, lcsh:Medicine (General), Decision analysis, Decision-making
Abstract: Background Calls have been made for greater application of the decision sciences to investigate and improve use of research evidence in mental health policy and practice. This article proposes a novel method, “decision sampling,” to improve the study of decision-making and research evidence use in policy and programmatic innovation. An illustrative case study applies the decision sampling framework to investigate the decisions made by mid-level administrators when developing system-wide interventions to identify and treat the trauma of children entering foster care. Methods Decision sampling grounds qualitative inquiry in decision analysis to elicit information about the decision-making process. Our case study engaged mid-level managers in public sector agencies (n = 32) from 12 states, anchoring responses on a recent index decision regarding universal trauma screening for children entering foster care. Qualitative semi-structured interviews inquired on questions aligned with key components of decision analysis, systematically collecting information on the index decisions, choices considered, information synthesized, expertise accessed, and ultimately the values expressed when selecting among available alternatives. Results Findings resulted in identification of a case-specific decision set, gaps in available evidence across the decision set, and an understanding of the values that guided decision-making. Specifically, respondents described 14 inter-related decision points summarized in five domains for adoption of universal trauma screening protocols, including (1) reach of the screening protocol, (2) content of the screening tool, (3) threshold for referral, (4) resources for screening startup and sustainment, and (5) system capacity to respond to identified needs. Respondents engaged a continuum of information that ranged from anecdote to research evidence, synthesizing multiple types of knowledge with their expertise. Policy, clinical, and delivery system experts were consulted to help address gaps in available information, prioritize specific information, and assess “fit to context.” The role of values was revealed as participants evaluated potential trade-offs and selected among policy alternatives. Conclusions The decision sampling framework is a novel methodological approach to investigate the decision-making process and ultimately aims to inform the development of future dissemination and implementation strategies by identifying the evidence gaps and values expressed by the decision-makers, themselves.
Published: 2021

20. Barriers to university–industry collaboration in an emerging market: firm-level evidence from Turkey

Author: Timo Kleiner-Schäfer and Kerstin J. Schaefer
Subjects: HB Economic Theory, HD Industries. Land use. Labor, Accounting, General Engineering, Business and International Management
Abstract: University-industry collaborations (UICs) are one of the main sources of external knowledge and technologies for industrial firms, particularly in the context of emerging markets (EMs) and firm development. It is thus highly relevant to identify potential barriers internal to the firm as well as in the regional innovation system that might prevent firms from using UICs for innovation, in particular in an EM context. In order to address this issue, we conduct a firm-level study of the R&D-related segment of the manufacturing industry in Istanbul. Logistic regression analysis is used to test the effect of potential barriers on using UICs for innovative activities. With this approach, we are able to identify barriers that prevent innovation-related UICs and thus form a bottleneck to collaborations in the first place. Our findings show that lack of information about UIC opportunities as well as lack of financial support for UICs are the most relevant barriers that inhibit firms’ usage of UICs for innovation. This firm-level evidence points out the importance of university technology transfer offices in regional innovation systems and for fruitful UICs. We further find that administrative barriers have no significant effect, while barriers related to trust and skill matching with scientific partners even have a reverse effect to what we would have expected from the literature. This finding might point towards an effect of perceived versus deterring barriers that has been observed in innovation studies before and might be relevant for studying UICs as well.
Published: 2022

21. Therapeutic vascularization in regenerative medicine

Author: Maximilian G. Burger, Andrea Banfi, Lorenz Gürke, Nunzia Di Maggio, Dirk J. Schaefer, Ludovic Melly, Roberto Gianni-Barrera, and Edin Mujagic
Subjects: 0301 basic medicine, Angiogenesis, medicine.medical_treatment, extracellular matrix, Neovascularization, Physiologic, ischemia, Protein Engineering, Regenerative Medicine, Concise Reviews, Regenerative medicine, Monocytes, Neovascularization, Extracellular matrix, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Animals, Humans, Medicine, Therapeutic angiogenesis, Progenitor cell, lcsh:QH573-671, lcsh:R5-920, vascular endothelial growth factor, Concise Review, business.industry, lcsh:Cytology, Growth factor, Gene Transfer Techniques, Cell Biology, General Medicine, 3. Good health, Vascular endothelial growth factor, 030104 developmental biology, chemistry, tissue engineering, Cancer research, medicine.symptom, neovascularization, Pericytes, business, lcsh:Medicine (General), 030217 neurology & neurosurgery, genetic therapy, Developmental Biology
Abstract: Therapeutic angiogenesis, that is, the generation of new vessels by delivery of specific factors, is required both for rapid vascularization of tissue‐engineered constructs and to treat ischemic conditions. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis. However, uncontrolled expression can lead to aberrant vascular growth and vascular tumors (angiomas). Major challenges to fully exploit VEGF potency for therapy include the need to precisely control in vivo distribution of growth factor dose and duration of expression. In fact, the therapeutic window of VEGF delivery depends on its amount in the microenvironment around each producing cell rather than on the total dose, since VEGF remains tightly bound to extracellular matrix (ECM). On the other hand, short‐term expression of less than about 4 weeks leads to unstable vessels, which promptly regress following cessation of the angiogenic stimulus. Here, we will briefly overview some key aspects of the biology of VEGF and angiogenesis and discuss their therapeutic implications with a particular focus on approaches using gene therapy, genetically modified progenitors, and ECM engineering with recombinant factors. Lastly, we will present recent insights into the mechanisms that regulate vessel stabilization and the switch between normal and aberrant vascular growth after VEGF delivery, to identify novel molecular targets that may improve both safety and efficacy of therapeutic angiogenesis., Therapeutic angiogenesis, that is, the generation of new blood vessels by delivery of specific factors, is required both for rapid vascularization of tissue‐engineered constructs and to treat ischemic conditions. A better understanding of the physiological mechanisms of vascular growth is important to exploit its therapeutic potential and for the rational design of cell, gene, and protein therapy approaches.
Published: 2020

22. Cherenkov Telescope Array : the World’s largest VHE gamma-ray observatory

Author: Roberta Zanin, H. Abdalla, H. Abe, S. Abe, A. Abusleme, F. Acero, A. Acharyya, V. Acin Portella, K. Ackley, R. Adam, C. Adams, S.S. Adhikari, I. Aguado Ruesga, I. Agudo, R. Aguilera, A. Aguirre Santaella, F. Aharonian, A. Alberdi, R. Alfaro, J. Alfaro, C. Alispach, R. Aloisio, R. Alves Batista, J.P. Amans, L. Amati, E. Amato, L. Ambrogi, G. Ambrosi, M. Ambrosio, R. Ammendola, J. Anderson, M. Anduze, E.O. Anguner, L.A. Antonelli, V. Antonuccio, P. Antoranz, R. Anutarawiramkul, J. Aragunde Gutierrez, C. Aramo, A. Araudo, M. Araya, A. Arbet Engels, C. Arcaro, V. Arendt, C. Armand, T. Armstrong, F. Arqueros, L. Arrabito, B. Arsioli, M. Artero, K. Asano, Y. Ascasibar, J. Aschersleben, M. Ashley, P. Attina, P. Aubert, C. B. Singh, D. Baack, A. Babic, M. Backes, V. Baena, S. Bajtlik, A. Baktash, C. Balazs, M. Balbo, O. Ballester, J. Ballet, B. Balmaverde, A. Bamba, R. Bandiera, A. Baquero Larriva, P. Barai, C. Barbier, V. Barbosa Martins, M. Barcelo, M. Barkov, M. Barnard, L. Baroncelli, U. Barres de Almeida, J.A. Barrio, D. Bastieri, P.I. Batista, I. Batkovic, C. Bauer, R. Bautista González, J. Baxter, U. Becciani, J. Becerra González, Y. Becherini, G. Beck, J. Becker Tjus, W. Bednarek, A. Belfiore, L. Bellizzi, R. Belmont, W. Benbow, D. Berge, E. Bernardini, M.I. Bernardos, K. Bernlöhr, A. Berti, M. Berton, B. Bertucci, V. Beshley, N. Bhatt, S. Bhattacharyya, W. Bhattacharyya, B. Y. Bi, G. Bicknell, N. Biederbeck, C. Bigongiari, A. Biland, R. Bird, E. Bissaldi, J. Biteau, M. Bitossi, O. Blanch, M. Blank, J. Blazek, J. Bobin, C. Boccato, F. Bocchino, C. Boehm, M. Bohacova, C. Boisson, J. Boix, J.P. Bolle, J. Bolmont, G. Bonanno, C. Bonavolontà, L. Bonneau Arbeletche, G. Bonnoli, P. Bordas, J. Borkowski, R. Bose, D. Bose, Z. Bosnjak, E. Bottacini, Markus Böttcher, M.T. Botticella, C. Boutonnet, F. Bouyjou, V. Bozhilov, E. Bozzo, L. Brahimi, C. Braiding, S. Brau Nogue, S. Breen, J. Bregeon, M. Breuhaus, A. Brill, W. Brisken, E. Brocato, A.M. Brown, K. Brügge, P. Brun, F. Brun, L. Brunetti, G. Brunetti, P. Bruno, A. Bruno, A. Bruzzese, N. Bucciantini, J. H. Buckley, R. Bühler, A. Bulgarelli, T. Bulik, M. Bünning, M. Bunse, M. Burton, A. Burtovoi, M. Buscemi, S. Buschjager, G. Busetto, J. Buss, K. Byrum, A. Caccianiga, F. Cadoux, A. Calanducci, C. Calderon, J. Calvo Tovar, R. A. Cameron, P. Campana, R. Canestrari, F. Cangemi, B. Cantlay, M. Capalbi, M. Capasso, M. Cappi, A. Caproni, R. Capuzzo Dolcetta, P. Caraveo, V. Cárdenas, L. Cardiel, M. Cardillo, C. Carlile, S. Caroff, R. Carosi, A. Carosi, E. Carquin, M. Carrere, J.M. Casandjian, S. Casanova, F. Cassol, F. Catalani, O. Catalano, D. Cauz, A. Ceccanti, C. Celestino Silva, K. Cerny, M. Cerruti, E. Chabanne, P. Chadwick, Y. Chai, P. Chambery, C. Champion, S. Chaty, A. Chen, K. Cheng, M. Chernyakova, G. Chiaro, A. Chiavassa, M. Chikawa, V.R. Chitnis, J. Chudoba, L. Chytka, S. Cikota, A. Circiello, P. Clark, M. Colak, E. Colombo, S. Colonges, A. Comastri, A. Compagnino, V. Conforti, E. Congiu, R. Coniglione, J. Conrad, F. Conte, J.L. Contreras, P. Coppi, R. Cornat, J. Coronado Blazquez, J. Cortina, A. Costa, H. Costantini, G. Cotter, B. Courty, S. Covino, S. Crestan, P. Cristofari, R. Crocker, J. Croston, K. Cubuk, O. Cuevas, X. Cui, G. Cusumano, S. Cutini, G. D'Amico, F. D'Ammando, P. D'Avanzo, P. Da Vela, M. Dadina, S. Dai, M. Dalchenko, M. Dall'Ora, M.K. Daniel, J. Dauguet, I. Davids, J. Davies, B. Dawson, A. De Angelis, A.E. de Araujo Carvalho, M. de Bony de Lavergne, G. De Cesare, F. de Frondat, I. de la Calle, E. de Gouveia Dal Pino, B. De Lotto, A. De Luca, D. De Martino, M. de Naurois, E. de Ona Wilhelmi, F. De Palma Persio, N. De Simone, V. de Souza Valle, E. Delagnes, G. Deleglise Reznicek, C. Delgado, A.G. Delgado Giler, J. Delgado Mengual Valle, Domenico Della Volpe, D. Depaoli, J. Devin, T. Di Girolamo, C. Di Giulio Pierro, L. Di Venere, C. Díaz, C. Dib, S. Diebold, S. Digel, A. Djannati Atai, J. Djuvsland, A. Dmytriiev, K. Docher, A. Domínguez, D. Dominis Prester, A. Donini, D. Dorner, M. Doro, Rita Cassia dos Anjos, J.L. Dournaux, T. Downes, G. Drake, H. Drass, D. Dravins, C. Duangchan, A. Duara, G. Dubus, L. Ducci, C. Duffy, D. Dumora, K. Dundas Mora, A. Durkalec, V.V. Dwarkadas, J. Ebr, C. Eckner, J. Eder, E. Edy, K. Egberts, S. Einecke, C. Eleftheriadis, D. Elsässer, G. Emery, D. Emmanoulopoulos, J.P. Ernenwein, M. Errando, P. Escarate, J. Escudero, C. Espinoza, S. Ettori, A. Eungwanichayapant, P. Evans, C. Evoli, M. Fairbairn, D. Falceta Goncalves, A. Falcone, V. Fallah Ramazanı, R. Falomo, K. Farakos, G. Fasola, A. Fattorini, Y. Favre, R. Fedora, E. Fedorova, K. Feijen, Q. Feng, G. Ferrand, G. Ferrara, O. Ferreira, M. Fesquet, E. Fiandrini, A. Fiasson, M. Filipovic, D. Fink, J.P. Finley, V. Fioretti, D.F.G. Fiorillo, M. Fiorini, S. Flis, H. Flores, L. Foffano, C. Fohr, M.V. Fonseca, L. Font, G. Fontaine, O. Fornieri, P. Fortin, L. Fortson, N. Fouque, B. Fraga, A. Franceschini, F.J. Franco, L. Freixas Coromina, L. Fresnillo, D. Fugazza, Y. Fujita, S. Fukami, Y. Fukazawa, D. Fulla, S. Funk, A. Furniss, S. Gabici, D. Gaggero, G. Galanti, P. Galdemard, Y. A. Gallant, D. Galloway, S. Gallozzi, V. Gammaldi, R. Garcia, L. E. García-Muñoz, E. Garcia Lopez, F. Gargano, C. Gargano, S. Garozzo, D. Gascon, T. Gasparetto, D. Gasparrini, H. Gasparyan, M. Gaug, N. Geffroy, A. Gent, S. Germani, A. Ghalumyan, A. Ghedina, G. Ghirlanda, F. Gianotti, S. Giarrusso, M. Giarrusso, G. Giavitto, B. Giebels, N. Giglietto, V. Gika, F. Gillardo, R. Gimenes, F. Giordano, E. Giro, M. Giroletti, Andrea Giuliani, M. Gjaja, J.F. Glicenstein, P. Gliwny, H. Goksu, P. Goldoni, J.L. Gomez, M.M. Gonzalez, Juan Manuel Gonzalez, K.S. Gothe, D. Gotz Coelho, T. Grabarczyk, R. Graciani, P. Grandi, G. Grasseau, D. Grasso, D. Green, J. Green, T. Greenshaw, P. Grespan, A. Grillo, M.H. Grondin, J. Grube, V. Guarino, B. Guest, O. Gueta, M. Günduz, S. Gunji, G. Gyuk, J. Hackfeld, D. Hadasch, L. Hagge, A. Hahn, J.E. Hajlaoui, A. Halim, P. Hamal, W. Hanlon, Y. Harada, M.J. Hardcastle, M. Harvey Collado, T. Haubold, A. Haupt, M. Havelka, K. Hayashi, M. Hayashida, H. He, L. Heckmann, M. Heller, F. Henault, Gilles Henri, G. Hermann, S. Hernández Cadena, J. Herrera Llorente, O. Hervet, J. Hinton, A. Hiramatsu, K. Hirotani, B. Hnatyk, R. Hnatyk, J.K. Hoang, D. H.H. Hoffmann, C. Hoischen, J. Holder, M. Holler, B. Hona, D. Horan, Dieter Horns, P. Horvath, J. Houles, M. Hrabovsky, D. Hrupec, Y. Huang, J.‑M. Huet, G. Hughes, G. Hull, T.B. Humensky, M. Hütten, M. Iarlori, J.M. Illa, R. Imazawa, T. Inada, F. Incardona, A. Ingallinera, S. Inoue, T. Inoue, Y. Inoue, F. Iocco, K. Ioka, M. Ionica, S. Iovenitti, A. Iriarte, K. Ishio, W. Ishizaki, Y. Iwamura, J. Jacquemier, M. Jacquemont, M. Jamrozy, P. Janecek, F. Jankowsky, A. JardinBlicq, C. Jarnot, P. Jean Martínez, L. Jocou, N. Jordana, M. Josselin, I. JungRichardt, F.J.P.A. Junqueira, C. Juramy Gilles, P. Kaaret, L.H.S. Kadowaki, M. Kagaya, R. Kankanyan, D. Kantzas, V. Karas, A. Karastergiou, S. Karkar, J. Kasperek, H. Katagiri, J. Kataoka, K. Katarzynski, S. Katsuda, N. Kawanaka, D. Kazanas, D. Kerszberg, B. Khélifi, M.C. Kherlakian, T.P. Kian, D.B. Kieda, T. Kihm, S. Kim, S. Kisaka, R. Kissmann, R. Kleijwegt, G. Kluge, W. Kluźniak, J. Knapp, A. Kobakhidze, Y. Kobayashi, B. Koch, J. Kocot, K. Kohri, N. Komin, A. Kong, K. Kosack, F. Krack, M. Krause, F. Krennrich, H. Kubo, V. N. Kudryavtsev, S. Kunwar, J. Kushida, P. Kushwaha, Barbera Parola, G. La Rosa, R. Lahmann, A. Lamastra, M. Landoni, D. Landriu, R.G. Lang, J. Lapington, P. Laporte, P. Lason, J. Lasuik, J. Lazendic Galloway, T. Le Flour, P. Le Sidaner, S. Leach, S.H. Lee, W.H. Lee, S. Lee Oliveira, A. Lemiere, M. Lemoine Goumard, J.P. Lenain, F. Leone, V. Leray, G. Leto, F. Leuschner, R. Lindemann, E. Lindfors, L. Linhoff, I. Liodakis, A. Lipniacka, M. Lobo, Thomas Lohse, S. Lombardi, A. Lopez, M. Lopez, R. Lopez Coto, F. Louis, M. Louys, F. Lucarelli, H. Ludwig Boudi, P.L. Luque Escamilla, M.C. Maccarone, E. Mach, A.J. Maciejewski, J. Mackey, P. Maeght, C. Maggio, G. Maier, P. Majumdar, M. Makariev, M. Mallamaci, R. Malta Nunes de Almeida, D. Malyshev, D. Mandat, G. Maneva, M. Manganaro, P. Manigot, K. Mannheim, N. Maragos, D. Marano, M. Marconi, A. Marcowith, M. Marculewicz, B. Marcun, J. Marin, N. Marinello, P. Marinos, S. Markoff, P. Marquez, G. Marsella, J. M. Martin, P. G. Martin, M. Martinez, G. Martinez, O. Martinez, H. Martinez Huerta, C. Marty, R. Marx, N. Masetti, P. Massimino, H. Matsumoto, N. Matthews, G. Maurin, W. Max Moerbeck, N. Maxted, M.N. Mazziotta, S.M. Mazzola, J.D. Mbarubucyeye, L. Mc Comb, I. McHardy, S. McKeague, S. McMuldroch, E. Medina, D. Medina Miranda, A. Melandri, C. Melioli, D. Melkumyan, S. Menchiari, S. Mereghetti, G. Merino Arevalo, E. Mestre, J.L. Meunier, T. Meures, S. Micanovic, M. Miceli, M. Michailidis, J. Michalowski, T. Miener, I. Mievre, J. D. Miller, T. Mineo, M. Minev, J.M. Miranda, A. Mitchell, T. Mizuno, B. A. Mode, R. Moderski, L. Mohrmann, E. Molinari, T. Montaruli, I. Monteiro, C. Moore, A. Moralejo, D. Morcuende Parrilla, E. Moretti, K. Mori, P. Moriarty, K. Morik, P. Morris, A. Morselli, K. Mosshammer, R. Mukherjee, J. Muller, C. Mundell, J. Mundet, T. Murach, A. Muraczewski, H. Muraishi, I. Musella, A. Musumarra, A. Nagai, S. Nagataki, T. Naito, T. Nakamori, K. Nakashima, K. Nakayama, N. Nakhjiri, G. Naletto, D. Naumann, L. Nava, M.A. Nawaz, H. Ndiyavala, D. Neise, L. Nellen, R. Nemmen, N. Neyroud, K. Ngernphat, T. Nguyen Trung, L. Nicastro, L. Nickel, J. Niemiec, D. Nieto, C. Nigro, M. Nikołajuk, D. Ninci, K. Noda, Y. Nogami, S. Nolan, R. P. Norris, D. Nosek, M. Nöthe, V. Novotny, S. Nozaki, F. Nunio, P. O'Brien, K. Obara, Y. Ohira, M. Ohishi, S. Ohm, T. Oka, N. Okazaki, A. Okumura, C. Oliver, G. Olivera, B. Olmi, M. Orienti, R. Orito, M. Orlandini, E. Orlando, J.P. Osborne, M. Ostrowski, N. Otte, E. Ovcharov, E. Owen, I. Oya, A. Ozieblo, M. Padovani, A. Pagliaro, A. Paizis, M. Palatiello, M. Palatka, E. Palazzi, J.‑L. Panazol, D. Paneque, S. Panny, Francesca Romana Pantaleo, M. Panter, M. Paolillo, A. Papitto, A. Paravac, J.M. Paredes, G. Pareschi, N. Parmiggiani, R.D. Parsons, P. Paśko, S. R. Patel, B. Patricelli, L. Pavletic, S. Pavy, A. Peer, M. Pecimotika, M.G. Pellegriti, P. Peñil Del Campo, A. Pepato, S. Perard, C. Perennes, M. Peresano, A. Perez Aguilera, J. Perez Romero, M.A. Perez Torres, M. Persic, P. O. Petrucci, O. Petruk, B. Peyaud, K. Pfrang, E. Pian, P. Piatteli, E. Pietropaolo, R. Pillera, D. Pimentel, F. Pintore, C. Pio Garcia, G. Pirola, F. Piron, S. Pita, M. Pohl, V. Poireau, A. Pollo, M. Polo, C. Pongkitivanichkul, J. Porthault, J. Powell, D. Pozo, R.R. Prado, E. Prandini, J. Prast, K. Pressard, G. Principe, N. Produit, D. Prokhorov, H. Prokoph, H. Przybilski, E. Pueschel, G. Pühlhofer, I. Puljak, M.L. Pumo, M. Punch, F. Queiroz, J. Quinn, A. Quirrenbach, P.J. Rajda, R. Rando, S. Razzaque, S. Recchia, P. Reichherzer, O. Reimer, A. Reisenegger, Q. Remy, M. Renaud, T. Reposeur, B. Reville, J.M. Reymond, J. Reynolds, D. Ribeiro, M. Ribo, G. Richards, J. Rico, F. Rieger, L. Riitano, M. Riquelme, D. Riquelme, S. Rivoire, V. Rizi, E. Roache, M. Roche, J. Rodriguez, G. Rodriguez Fernandez, J.C. Rodriguez Ramirez, J.J. Rodriguez Vazquez, G. Rojas, P. Romano, G. Romeo Lobato, C. Romoli, M. Roncadelli, J. Rosado, A. Rosales de Leon, G. Rowell, A. Rugliancich, J.E. Ruiz del Mazo, C. Rulten, C. Russell, F. Russo Hatlen, S. Safi Harb, L. Saha, V. Sahakian, S. Sailer, T. Saito, N. Sakaki, S. Sakurai, G. Salina, H. Salzmann, D. Sanchez, H. Sandaker, A. Sandoval, P. Sangiorgi, M. Sanguillon, H. Sano, M. Santander, A. Santangelo, R. Santos Lima, A. Sanuy, L. Sapozhnikov, T. Saric, S. Sarkar, H. Sasaki, N. Sasaki, Y. Sato, F.G. Saturni, M. Sawada, J. Schaefer, A. Scherer, J. Scherpenberg, P. Schipani, B. Schleicher, J. Schmoll, M. Schneider, H. Schoorlemmer, P. Schovanek, F. Schussler, B. Schwab, U. Schwanke, J. Schwarz, E. Sciacca, S. Scuderi, M. Seglar Arroyo, I. Seitenzahl, D. Semikoz, O. Sergijenko, J.E. Serna Franco, Karol Seweryn, V. Sguera, A. Shalchi, R.Y. Shang, P. Sharma, L. Sidoli, J. Sieiro, H. Siejkowski, A. Sillanpaa, B.B. Singh, K.K. Singh, A. Sinha, C. Siqueira, J. Sitarek, P. Sizun, V. Sliusar, D. Sobczynska, R.W. Sobrinho, H. Sol, G. Sottile, H. Spackman, S. Spencer, G. Spengler, D. Spiga, W. Springer, A. Stamerra, S. Stanic, R. Starling, Ł. Stawarz, Stanislav Stefanik, C. Stegmann, A. Steiner, S. Steinmassl, C. Stella, R. Sternberger, M. Sterzel, C. Stevens, B. Stevenson, T. Stolarczyk, G. Stratta, U. Straumann, J. Striskovic, M. Strzys, R. Stuik, M. Suchenek, Y. Sunada, Tiina Suomijarvi, T. Suric, H. Suzuki, P. Swierk, T. Szepieniec, K. Tachihara, G. Tagliaferri, H. Tajima, N. Tajima, D. Tak, H. Takahashi, M. Takahashi, J. Takata, R. Takeishi, T. Tam, M. Tanaka, T. Tanaka, S. Tanaka, M. Tavani, F. Tavecchio, T. Tavernier, A. Russ Taylor, L.A. Tejedor, P. Temnikov, K. Terauchi, J.C. Terrazas, R. Terrier, T. Terzic, M. Teshima, D. Thibaut, F. Thocquenne, W. Tian, L. Tibaldo, A. Tiengo, M. Tluczykont, C.J. Todero Peixoto, K. Toma, L. Tomankova, J. Tomastik, M. Tornikoski, D.F. Torres, E. Torresi, G. Tosti, L. Tosti, N. Tothill, F. Toussenel, G. Tovmassian, C. Trichard, M. Trifoglio, A. Trois, S. Truzzi, A. Tsiahina, B. Turk, A. Tutone, Y. Uchiyama, P. Utayarat, L. Vaclavek, M. Vacula, V. Vagelli, F. Vagnetti, J.A. Valdivia, M. Valentino, A. Valio, B. Vallage, P. Vallania Quispe, A.M. van den Berg, W. van Driel, C. van Eldik, C. van Rensburg, Brian van Soelen, J. Vandenbroucke, G. Vasileiadis, V. Vassiliev, M. Vazquez Acosta, M. Vecchi, A. Vega, J. Veh, P. Veitch, C. Venter, S. Ventura, S. Vercellone, V. Verguilov, G. Verna, S. Vernetto, V. Verzi, G.P. Vettolani, C. Veyssiere, I. Viale, A. Viana, N. Viaux, J. Vignatti, C.F. Vigorito, J. Villanueva, V. Vitale, V. Vittorini, V. Vodeb, N. Vogel, V. Voisin, S. Vorobiov, M. Vrastil, T. Vuillaume, S.J. Wagner, P. Wagner, K. Wakazono, S.P. Wakely, M. Ward, D. Warren, J. Watson, M. Wechakama, P. Wegner, A. Weinstein, C. Weniger, F. Werner, H. Wetteskind, M. L. White, A. Wierzcholska, S. Wiesand, R. Wijers, M. Wilkinson, M. Will, J. Williams, T. J. Williamson, A. Wolter, Y.W. Wong, M. Wood, T. Yamamoto, H. Yamamoto, Y. Yamane, R. Yamazaki, S. Yanagita, L. Yang, S. Yoo, T. Yoshida, T. Yoshikoshi, P. Yu, A. Yusafzai, Michael Zacharias, B. Zaldivar, L. Zampieri, R. Zanin, R. Zanmar Sanchez, D. Zaric, M. Zavrtanik, D. Zavrtanik, Andrzej Zdziarski, A. Zech, H. Zechlin, A. Zenin, A. Zerwekh, K. Ziętara, A. Zink, J. Ziolkowski, M. Zivec, A. Zmija, Współautorami artykułu są członkowie CTA Observatory, CTA Consortium i LST Collaboration w liczbie 1139, Astronomy, Research unit Nuclear & Hadron Physics, and Research unit Astroparticle Physics
Subjects: Physics, Observatory, Gamma ray, Astronomy
Abstract: Very-high Energy (VHE) gamma-ray astroparticle physics is a relatively young field, and observations over the past decade have surprisingly revealed almost two hundred VHE emitters which appear to act as cosmic particle accelerators. These sources are an important component of the Universe, influencing the evolution of stars and galaxies. At the same time, they also act as a probe of physics in the most extreme environments known - such as in supernova explosions, and around or after the merging of black holes and neutron stars. However, the existing experiments have provided exciting glimpses, but often falling short of supplying the full answer. A deeper understanding of the TeV sky requires a significant improvement in sensitivity at TeV energies, a wider energy coverage from tens of GeV to hundreds of TeV and a much better angular and energy resolution with respect to the currently running facilities. The next generation gamma-ray observatory, the Cherenkov Telescope Array Observatory (CTAO), is the answer to this need. In this talk I will present this upcoming observatory from its design to the construction, and its potential science exploitation. CTAO will allow the entire astronomical community to explore a new discovery space that will likely lead to paradigm-changing breakthroughs. In particular, CTA has an unprecedented sensitivity to short (sub-minute) timescale phenomena, placing it as a key instrument in the future of multi-messenger and multi-wavelength time domain astronomy. I will conclude the talk presenting the first scientific results obtained by the LST-1, the prototype of one CTAO telescope type - the Large-Sized Telescope, that is currently under commission., PoS: Proceedings of Science, 395, ISSN:1824-8039, Proceedings of 37th International Cosmic Ray Conference (ICRC2021)
Published: 2022

23. VP3: Breast Reduction: A Ten-Year Retrospective Review of the Omega Resection Technique

Author: Juan A. Viscardi, C. M. Oranges, D. J. Schaefer, and D. F. Kalbermatten
Subjects: RD1-811, Surgery, Saturday, August 28, 2021, Abstract
Published: 2022

24. Case Report: Reconstruction of a Large Maxillary Defect With an Engineered, Vascularized, Prefabricated Bone Graft

Author: Tarek Ismail, Alexander Haumer, Alexander Lunger, Rik Osinga, Alexandre Kaempfen, Franziska Saxer, Anke Wixmerten, Sylvie Miot, Florian Thieringer, Joerg Beinemann, Christoph Kunz, Claude Jaquiéry, Thomas Weikert, Felix Kaul, Arnaud Scherberich, Dirk J. Schaefer, and Ivan Martin
Subjects: graft prefabrication, Cancer Research, Oncology, regenerative surgery, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, complex 3D bone defect, Case Report, bone–soft tissue interface, vascularized composite graft, RC254-282
Abstract: The reconstruction of complex midface defects is a challenging clinical scenario considering the high anatomical, functional, and aesthetic requirements. In this study, we proposed a surgical treatment to achieve improved oral rehabilitation and anatomical and functional reconstruction of a complex defect of the maxilla with a vascularized, engineered composite graft. The patient was a 39-year-old female, postoperative after left hemimaxillectomy for ameloblastic carcinoma in 2010 and tumor-free at the 5-year oncological follow-up. The left hemimaxillary defect was restored in a two-step approach. First, a composite graft was ectopically engineered using autologous stromal vascular fraction (SVF) cells seeded on an allogenic devitalized bone matrix. The resulting construct was further loaded with bone morphogenic protein-2 (BMP-2), wrapped within the latissimus dorsi muscle, and pedicled with an arteriovenous (AV) bundle. Subsequently, the prefabricated graft was orthotopically transferred into the defect site and revascularized through microvascular surgical techniques. The prefabricated graft contained vascularized bone tissue embedded within muscular tissue. Despite unexpected resorption, its orthotopic transfer enabled restoration of the orbital floor, separation of the oral and nasal cavities, and midface symmetry and allowed the patient to return to normal diet as well as to restore normal speech and swallowing function. These results remained stable for the entire follow-up period of 2 years. This clinical case demonstrates the safety and the feasibility of composite graft engineering for the treatment of complex maxillary defects. As compared to the current gold standard of autologous tissue transfer, this patient’s benefits included decreased donor site morbidity and improved oral rehabilitation. Bone resorption of the construct at the ectopic prefabrication site still needs to be further addressed to preserve the designed graft size and shape.
Published: 2021

25. Genetic Variation and the Distribution of Variant Types in the Horse

Author: Molly E. McCue, Robert J. Schaefer, James R. Mickelson, S. A. Durward-Akhurst, B. Grantham, and W. K. Carey
Subjects: Whole genome sequencing, medicine.medical_specialty, whole genome sequence, Biology, QH426-470, Genome, Phenotype, breed differences, variant discovery, Evolutionary biology, Genetic variation, Genotype, genetic variation, medicine, Genetics, Medical genetics, Molecular Medicine, Allele frequency, Genetics (clinical), Reference genome, Original Research, equine
Abstract: Genetic variation is a key contributor to health and disease. Understanding the link between an individual’s genotype and the corresponding phenotype is a major goal of medical genetics. Whole genome sequencing (WGS) within and across populations enables highly efficient variant discovery and elucidation of the molecular nature of virtually all genetic variation. Here, we report the largest catalog of genetic variation for the horse, a species of importance as a model for human athletic and performance related traits, using WGS of 534 horses. We show the extent of agreement between two commonly used variant callers. In data from ten target breeds that represent major breed clusters in the domestic horse, we demonstrate the distribution of variants, their allele frequencies across breeds, and identify variants that are unique to a single breed. We investigate variants with no homozygotes that may be potential embryonic lethal variants, as well as variants present in all individuals that likely represent regions of the genome with errors, poor annotation or where the reference genome carries a variant. Finally, we show regions of the genome that have higher or lower levels of genetic variation compared to the genome average. This catalog can be used for variant prioritization for important equine diseases and traits, and to provide key information about regions of the genome where the assembly and/or annotation need to be improved.
Published: 2021
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26. Disease Association of Anti‒Carboxyethyl Lysine Autoantibodies in Hidradenitis Suppurativa

Author: Giulio Macchiarella, Vanessa Cornacchione, Celine Cojean, Julia Riker, Yichen Wang, Helene Te, Melanie Ceci, Johann E. Gudjonsson, Swann Gaulis, Jean François Goetschy, Audrey Wollschlegel, Stephanie K. Gass, Sofia Oetliker-Contin, Barbara Wettstein-Ling, Dirk J. Schaefer, Pascale Meschberger, Roland de Roche, Rik Osinga, Grazyna Wieczorek, Ulrike Naumann, Joachim C.U. Lehmann, Anna Schubart, Andreas Hofmann, Lukas Roth, Edwin F. Florencia, Christian Loesche, Elisabetta Traggiai, Alexandre Avrameas, Errol P. Prens, Till A. Röhn, Ben Roediger, and Dermatology
Subjects: Cell Biology, Dermatology, Molecular Biology, Biochemistry
Abstract: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurring suppurating lesions of the intertriginous areas, resulting in a substantial impact on patients’ QOL. HS pathogenesis remains poorly understood. An autoimmune component has been proposed, but disease-specific autoantibodies, autoantigens, or autoreactive T cells have yet to be described. In this study, we identify a high prevalence of IgM, IgG, and IgA antibodies directed against Nε-carboxyethyl lysine (CEL), a methylglyoxal-induced advanced glycation end-product, in the sera of patients with HS. Titers of anti-CEL IgG and IgA antibodies were highly elevated in HS compared with those in healthy controls and individuals with other inflammatory skin diseases. Strikingly, the majority of anti-CEL IgG was of the IgG2 subclass and correlated independently with both disease severity and duration. Both CEL and anti-CEL‒producing plasmablasts could be isolated directly from HS skin lesions, further confirming the disease relevance of this autoimmune response. Our data point to an aberration of the methylglyoxal pathway in HS and support an autoimmune axis in the pathogenesis of this debilitating disease.
Published: 2023

27. Gluteal Augmentation Techniques: A Comprehensive Literature Review

Author: Martin Haug, Mathias Tremp, Dirk J. Schaefer, Pietro G. di Summa, Daniel F. Kalbermatten, Carlo M. Oranges, and Yves Harder
Subjects: medicine.medical_specialty, business.industry, General Medicine, 030230 surgery, medicine.disease, Surgery, Transplantation, 03 medical and health sciences, 0302 clinical medicine, Patient satisfaction, medicine.anatomical_structure, Embolism, 030220 oncology & carcinogenesis, medicine, Implant, Surgical Flaps, Fat embolism, Buttocks, Complication, business
Abstract: Background: Many studies of gluteal augmentation techniques have been published in recent decades, including case reports, retrospective and prospective case series, and multicenter survey reviews. However, to date, there has been no study of the overall complications or satisfaction rates associated with the broad spectrum of techniques. Objectives: The authors performed a comprehensive literature review to determine outcomes and complications of gluteoplasty techniques, including patient satisfaction. Methods: A search on PubMed/Medline was performed for clinical studies involving gluteal augmentation techniques. A priori criteria were used to review the resulting articles. Results: Fifty-two studies, published from 1969 through 2015, were included - representing 7834 treated patients. Five gluteal augmentation techniques were identified from these studies: gluteal augmentation with implants (n = 4781), autologous fat grafting (n = 2609), local flaps (n = 369), hyaluronic acid gel injection (n = 69), and local tissue rearrangement (n = 6). The overall complication rates of the most commonly utilized techniques were: 30.5% for gluteal augmentation with implants, 10.5% for autologous fat grafting, and 22% for local flaps. Patients' satisfaction was reported as consistently high for all the five techniques. Conclusions: Implant-based gluteal augmentation is associated with high patients' satisfaction despite a high complication rate, while autologous fat grafting is associated with the lowest complication rate yet including serious major complications such as fat embolism. Local flaps and local tissue rearrangements are the ideal procedures in case of massive weight loss patients. A paucity of data is available for hyaluronic acid gel injections, which appear to be effective but temporary and expensive. Level of Evidence: 4
Published: 2021

28. Multiple drug resistance in the canine hookworm Ancylostoma caninum: an emerging threat?

Author: Russell W. Avramenko, Sue B. Howell, John J. Schaefer, John S. Gilleard, Pablo David Jimenez Castro, and Ray M. Kaplan
Subjects: 0301 basic medicine, Resistance, Drug resistance, Breeding, Egg hatch assay, Feces, chemistry.chemical_compound, 0302 clinical medicine, Canine health, Pyrantel, Dog Diseases, Anthelmintic, Ancylostoma caninum, Anthelmintics, 0303 health sciences, biology, 030108 mycology & parasitology, Drug Resistance, Multiple, 3. Good health, Infectious Diseases, medicine.drug, Ancylostoma, 030231 tropical medicine, Polymorphism, Single Nucleotide, Milbemycin oxime, Ancylostomiasis, Microbiology, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Dogs, parasitic diseases, medicine, Animals, Helminths, lcsh:RC109-216, Parasite Egg Count, 030304 developmental biology, Research, biology.organism_classification, Virology, United States, Multiple drug resistance, Parasitology, chemistry, Hookworms, Hookworm Infections, Fenbendazole
Abstract: BackgroundThe canine hookworm,Ancylostoma caninumis the most prevalent and important intestinal nematode parasite of dogs in the USA. Hookworms are typically well controlled by treatment with all commonly used anthelmintics that are approved for this use in dogs. However, in the past few years, cases of recurrent/persistent canine hookworm infections appear to have dramatically increased, suggesting that anthelmintic resistance (AR) may have evolved in this parasite. These cases are highly overrepresented by greyhounds, but multiple other breeds are also represented. The aim of this study was to characterize several of these suspected resistant isolates usingin vitro, genetic and clinical testing to determine if these cases represent true anthelmintic resistance inA. caninum.MethodsFecal samples containing hookworm eggs from three cases of persistent hookworm infections; one from a greyhound, one from a miniature schnauzer and one from a hound-mix, were received by our laboratory. These were then used to establish infections in laboratory dogs and to perform egg hatch assays (EHA) and larval development assays (LDA) for detecting resistance to benzimidazoles and macrocyclic lactones, respectively. Additional EHA and LDA were performed on eggs recovered from the laboratory-induced infections. Fecal egg count reduction tests were performed to detect resistance to pyrantel. Deep amplicon sequencing assays were developed to measure the frequency of non-synonymous single nucleotide polymorphisms (SNP) at codons 167, 198 and 200 of theA. caninumisotype-1 β-tubulin gene.ResultsResistance ratios for the threeA. caninumisolates tested ranged from 6.0 to > 100 and 5.5 to 69.8 for the EHA and LDA, respectively. Following treatment with pyrantel, reduction in faecal egg counts was negative or 0%. Deep amplicon sequencing of the isotype-1 β-tubulin gene identified a high frequency of resistance-associated SNPs at codon 167 in all three resistant isolates and in two additional clinical cases.ConclusionsThese data conclusively demonstrate multiple anthelmintic resistance in multiple independent isolates ofA. caninum, strongly suggesting that this is an emerging problem in the USA. Furthermore, evidence suggest that these resistant hookworms originate from racing greyhound farms and kennels, though additional research is needed to confirm this.
Published: 2019

29. Mycoplasma haemolamae and intestinal parasite relationships with erythrocyte variables in clinically healthy alpacas and llamas

Author: John J. Schaefer, Ricardo Videla, Deanna M. W. Schaefer, Lisa C. Viesselmann, Aly Chapman, and Heidi M. Wyrosdick
Subjects: Male, 040301 veterinary sciences, Anemia, Physiology, Intestinal parasite, Standard Article, 030204 cardiovascular system & hematology, medicine.disease_cause, Real-Time Polymerase Chain Reaction, Trichostrongyloidiasis, 0403 veterinary science, Deworming, 03 medical and health sciences, Hemoglobins, 0302 clinical medicine, Mycoplasma, Medicine, Animals, Mycoplasma Infections, Hematolgoy, Parasite Egg Count, Feces, Eggs per gram, Whole blood, FOOD AND FIBER ANIMAL, lcsh:Veterinary medicine, General Veterinary, biology, Trichostrongyloidea, business.industry, fecal egg count, 04 agricultural and veterinary sciences, medicine.disease, biology.organism_classification, Tennessee, anemia, Standard Articles, hemoparasite, Cross-Sectional Studies, Hematocrit, Erythrocyte Count, camelid, lcsh:SF600-1100, Female, Hemoglobin, endoparasite, business, Camelids, New World, Camelid
Abstract: Background Mycoplasma haemolamae (Mhl) and gastrointestinal nematodes can cause anemia in camelids. Control programs aim to suppress parasitism without promoting anthelminthic resistance, but few evidence‐based guidelines define acceptable parasite loads in camelids. Hypothesis/Objectives In clinically healthy nonanemic camelids, compare erythrocyte variables to Mhl real‐time PCR status and to fecal egg count (FEC). Determine the FEC threshold above which erythrocyte variables are consistently below reference interval medians. Animals One hundred fourteen client‐owned adult alpacas and llamas. Methods In a cross‐sectional study, whole blood in ethylenediaminetetraacetic acid (EDTA) was assessed for packed cell volume (PCV) by centrifugation, erythrocyte count (RBC), and hemoglobin concentration (HGB) using an ADVIA120 analyzer, and Mhl using real‐time PCR. Trichostrongyle eggs per gram (epg) were counted by modified McMaster test on freshly collected feces. Significant differences in erythrocyte variables based on Mhl status and FEC thresholds were assessed by independent t test and one‐way ANOVA, respectively. Results Packed cell volume, RBC, and HGB were not significantly different between Mhl‐positive and Mhl‐negative animals, but were significantly lower in animals with FEC >1000 epg compared to those with 600 epg had RBC and HGB below the reference interval median. All animals with FEC >750 epg had PCV below the reference interval median. Conclusions and Clinical Importance In healthy nonanemic camelids, positive Mhl PCR is not associated with lower erythrocyte variables and such animals may not warrant treatment. Fecal egg count >600‐750 epg has a negative effect on erythrocyte variables, and may be a guide for deworming protocols.
Published: 2019

30. A Physiologically‐Based Pharmacokinetic Model for Targeting Calcitriol‐Conjugated Quantum Dots to Inflammatory Breast Cancer Cells

Author: Anja Nohe, Rachel J. Schaefer, Jonathon Gorky, Mallory Smith, Kenneth L. van Golen, Prasad Dhurjati, Margot Wagner, and James K Forder
Subjects: Immunoconjugates, Calcitriol, In silico, Antineoplastic Agents, Breast Neoplasms, Conjugated system, Inflammatory breast cancer, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Article, Mice, Drug Delivery Systems, Pharmacokinetics, Cell Line, Tumor, Quantum Dots, medicine, Animals, Humans, General Pharmacology, Toxicology and Pharmaceutics, skin and connective tissue diseases, MUC1, biology, Chemistry, lcsh:Public aspects of medicine, General Neuroscience, Research, lcsh:RM1-950, Mucin-1, technology, industry, and agriculture, lcsh:RA1-1270, General Medicine, Articles, medicine.disease, equipment and supplies, Xenograft Model Antitumor Assays, lcsh:Therapeutics. Pharmacology, Cell culture, Cancer research, biology.protein, Female, Antibody, medicine.drug
Abstract: Quantum dots (QDs) conjugated with 1,25 dihydroxyvitamin D3 (calcitriol) and Mucin‐1 (MUC‐1) antibodies (SM3) have been found to target inflammatory breast cancer (IBC) tumors and reduce proliferation, migration, and differentiation of these tumors in mice. A physiologically‐based pharmacokinetic model has been constructed and optimized to match experimental data for multiple QDs: control QDs, QDs conjugated with calcitriol, and QDs conjugated with both calcitriol and SM3 MUC1 antibodies. The model predicts continuous QD concentration for key tissues in mice distinguished by IBC stage (healthy, early‐stage, and late‐stage). Experimental and clinical efforts in QD treatment of IBC can be augmented by in silico simulations that predict the short‐term and long‐term behavior of QD treatment regimens.
Published: 2019

31. The horse Y chromosome as an informative marker for tracing sire lines

Author: Thomas Rattei, Markus Neuditschko, Stefan Rieder, Gottfried Brem, Sabine Felkel, Brandon D. Velie, Tosso Leeb, Georg Thaller, Ruedi Fries, Jan E. Janecka, Julia Metzger, Viktoria Dobretsberger, Doris Rigler, Terje Raudsepp, Christian Schlötterer, Molly E. McCue, Vidhya Jagannathan, Robert J. Schaefer, Carl-Johan Rubin, Ottmar Distl, Gabriella Lindgren, Bhanu P. Chowdhary, Claus Vogl, Barbara Wallner, and Jens Tetens
Subjects: Male, horse, Y chromosome, sire lines, VARIANT, DIVERSITY, SUITE, lcsh:Medicine, Breeding, Domestication, 0302 clinical medicine, Genetics and Breeding in Agricultural Sciences, Y Chromosome, PHYLOGENETIC ANALYSIS, Family history, lcsh:Science, Phylogeny, 0303 health sciences, Multidisciplinary, 630 Agriculture, ddc, Pedigree, Multidisciplinary Sciences, Science & Technology - Other Topics, 590 Animals (Zoology), Female, Biology, SEQUENCE, Article, REGION, 03 medical and health sciences, Phylogenetics, Genetic variation, Animals, Horses, Animal breeding, 030304 developmental biology, Science & Technology, MUTATIONS, Sire, Haplotype, lcsh:R, LINEAGES, Horse, Haplotypes, Evolutionary biology, ORIGINS, 570 Life sciences, biology, lcsh:Q, GENOMICS, 030217 neurology & neurosurgery, Genetik och förädling inom lantbruksvetenskap
Abstract: Analysis of the Y chromosome is the best-established way to reconstruct paternal family history in humans. Here, we applied fine-scaled Y-chromosomal haplotyping in horses with biallelic markers and demonstrate the potential of our approach to address the ancestry of sire lines. We de novo assembled a draft reference of the male-specific region of the Y chromosome from Illumina short reads and then screened 5.8 million basepairs for variants in 130 specimens from intensively selected and rural breeds and nine Przewalski's horses. Among domestic horses we confirmed the predominance of a young'crown haplogroup' in Central European and North American breeds. Within the crown, we distinguished 58 haplotypes based on 211 variants, forming three major haplogroups. In addition to two previously characterised haplogroups, one observed in Arabian/Coldblooded and the other in Turkoman/Thoroughbred horses, we uncovered a third haplogroup containing Iberian lines and a North African Barb Horse. In a genealogical showcase, we distinguished the patrilines of the three English Thoroughbred founder stallions and resolved a historic controversy over the parentage of the horse 'Galopin', born in 1872. We observed two nearly instantaneous radiations in the history of Central and Northern European Y-chromosomal lineages that both occurred after domestication 5,500 years ago. ispartof: SCIENTIFIC REPORTS vol:9 issue:1 ispartof: location:England status: published
Published: 2019
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32. ESPRAS Survey on Breast Reconstruction in Europe

Author: Mark Henley, Drahomír Palenčár, Marc Vandevoort, Klemen Rogelj, Nicholas Moellhoff, Fabio Santanelli di Pompeo, Emma Hansson, Elias Athanasopoulos, Lisbet Rosenkrantz Hölmich, Ruth Waters, Giovanni Di Benedetto, Aleksandra Bozovic Celebic, Andrzej Piatkowski, Rado Zic, Cenk Demirdöver, Olavi Vasar, Reuf Karabeg, Stephan Spendel, Hinne A. Rakhorst, Ulla Karhunen-Enckell, Horácio Costa, Alexandru Valentin Georgescu, Anna Elander, Dylan J. Murray, Elisabeth A. Kappos, Robert Caulfield, Thierry van Hemelryck, Christian Korvald, Riccardo E. Giunta, Dirk J. Schaefer, Stephane de Mortillet, Georgios Psaras, Carolina Andresen, Nenad Stepic, Plastische Chirurgie (PLC), MUMC+: MA Plastische Chirurgie (9), and RS: NUTRIM - R2 - Liver and digestive health
Subjects: Microsurgery, medicine.medical_specialty, Esthetics, Free Flap, Mammaplasty, Operating procedures, MEDLINE, DIEP, 030230 surgery, FLAP, POSTMASTECTOMY RADIATION-THERAPY, 03 medical and health sciences, plastic surgery, reconstruction, 0302 clinical medicine, Patient satisfaction, Consistency (negotiation), Surveys and Questionnaires, MASTECTOMY, Humans, Medicine, European standard, Orthopedics and Sports Medicine, CANCER PATIENTS, IMPLANT RECONSTRUCTION, Surgeons, PATIENT SATISFACTION, OUTCOMES, business.industry, ESPRAS, Breast Reconstruction Registry, Equity (finance), Europe, Breast Reconstruction, Clinical trial, Leadership, REGISTRY, 030220 oncology & carcinogenesis, Family medicine, IMMEDIATE, UPDATE, Surgery, business, Breast reconstruction
Abstract: The European Leadership Forum (ELF) of the European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS) previously identified the need for harmonisation of breast reconstruction standards in Europe, in order to strengthen the role of plastic surgeons. This study aims to survey the status, current trends and potential regional differences in the practice of breast reconstruction in Europe, with emphasis on equity and access. A largescale web-based questionnaire was sent to consultant plastic and reconstructive surgeons, who are experienced in breast reconstruction and with understanding of the national situation in their country. Suitable participants were identified via the Executive Committee (ExCo) of ESPRAS and national delegates of ESPRAS. The results were evaluated and related to evidence-based literature. A total of 33 participants from 29 European countries participated in this study. Overall, the incidence of breast reconstruction was reported to be relatively low across Europe, comparable to other large geographic regions, such as North America. Equity of provision and access to breast reconstruction was distributed evenly within Europe, with geographic regions potentially affecting the type of reconstruction offered. Standard practices with regard to radiotherapy differed between countries and a clear demand for European guidelines on breast reconstruction was reported. This study identified distinct lack of consistency in international practice patterns across European countries and a strong demand for consistent European guidance. Large-scale and multi-centre European clinical trials are required to further elucidate the presented areas of interest and to define European standard operating procedures. Im Rahmen des ELF der ESPRAS wurde die Notwendigkeit standardisierter Richtlinien zur Brustrekonstruktion auf europäischer Ebene definiert. Ziel dieser Studie ist es, zunächst einen Überblick über den aktuellen Status, Entwicklungen und mögliche regionale Unterschiede der Brustrekonstruktion in Europa zu geben, wobei ein Schwerpunkt auf dem Angebot, der Verteilung und dem Zugang zur Brustrekonstruktion liegt. Es erfolgte eine internetbasierte Befragung von in der Brustrekonstruktion spezialisierten Plastischen Chirurgen, welche zusätzlich die nationalen Versorgungsstrukturen ihrer jeweiligen Länder überblicken. Geeignete Teilnehmer wurden über das ExCo der ESPRAS und nationale Delegierte von ESPRAS identifiziert. Die Ergebnisse wurden mit aktueller evidenzbasierter Literatur verglichen. 33 Teilnehmer aus 29 europäischen Ländern nahmen an der Studie teil. Im Vergleich zur Gesamtzahl durchgeführter Mastektomien war die Inzidenz der Brustrekonstruktionen in Europa relativ gering, vergleichbar mit anderen großen geografischen Regionen, wie z. B. Nordamerika. Die Verfügbarkeit und der Zugang zur Brustrekonstruktion war innerhalb Europas gleichmäßig verteilt, allerdings kann die geografische Region das Verfahren der Brustrekonstruktion (Eigengewebe vs. Implantat) beeinflussen. Deutliche Differenzen zeigten sich bezüglich Brustrekonstruktionen bei bestrahlten Patientinnen. Die Studie identifizierte ein ausgeprägtes Maß an Inkohärenz in den internationalen Standards zwischen den europäischen Ländern. Es besteht großer Bedarf für kohärente europäische Leitlinien. Europäische, multizentrische klinische Studien sollten initiiert werden, um eine evidenzbasierte Grundlage zu schaffen.
Published: 2021

33. Rapid Discovery and Detection of Haemaphysalis longicornis through the Use of Passive Surveillance and Collaboration: Building a State Tick-Surveillance Network

Author: James D. Freye, Heidi M. Wyrosdick, John J. Schaefer, Rebecca A. Butler, Jennifer G. Chandler, K. W. Thompson, Daniel M. Grove, Sterling Daniels, Micah P. Willis, Kevin K. Lahmers, Samantha Beaty, Jennie Z. Ivey, James W. Mertins, Rebecca Trout Fryxell, D Paulsen, Denise L. Bonilla, Douglas Balthaser, Richard W. Gerhold, Joy Sweaney, Roger D. Applegate, and Dené N. Vann
Subjects: 0301 basic medicine, Health, Toxicology and Mutagenesis, 030231 tropical medicine, Wildlife, detection, Zoology, distribution zoonoses, Tick, 03 medical and health sciences, 0302 clinical medicine, parasitic diseases, OneHealth, Ehrlichia species, biology, business.industry, Public Health, Environmental and Occupational Health, biology.organism_classification, bacterial infections and mycoses, tick, collaboration, 030104 developmental biology, Geography, Parasitology, Epidemiological surveillance, Medicine, Livestock, Babesia species, Haemaphysalis longicornis, business
Abstract: Between March 2019 and February 2020, Asian long-horned ticks (Haemaphysalis longicornis Neumann, 1901) were discovered and collected for the first time in one middle and seven eastern Tennessee counties, facilitated by a newly developed passive and collaborative tick-surveillance network. Network collaborators included federal, state, county, university, and private resource personnel working with companion animals, livestock, and wildlife. Specimens were collected primarily from dogs and cattle, with initial detections of female adult stage ticks by stakeholders associated with parasitology positions (e.g., entomologists and veterinary parasitologists). Initial county tick detections were confirmed with morphological and molecular identifications, and then screened for the presence of animal-associated pathogens (Anaplasma marginale, Babesia species, Ehrlichia species, and Theileria orientalis), for which all tests were negative. Herein, we describe the identification and confirmation of these tick specimens as well as other results of the surveillance collaboration.
Published: 2021
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34. Prognostic Value of Urinary and Plasma C-Type Natriuretic Peptide in Acute Decompensated Heart Failure

Author: Horng H. Chen, Yang Chen, John C. Burnett, Andrew D. Rule, Xiao Ma, S. Jeson Sangaralingham, Christopher G. Scott, Seethalakshmi R. Iyer, Tomoko Ichiki, Jacob J. Schaefer, and Shawn Reginauld
Subjects: medicine.medical_specialty, Acute decompensated heart failure, medicine.drug_class, Urinary system, Renal function, Ventricular Function, Left, Article, Internal medicine, Natriuretic Peptide, Brain, Natriuretic peptide, Medicine, Humans, Heart Failure, Kidney, Ejection fraction, business.industry, Natriuretic Peptide, C-Type, Stroke Volume, medicine.disease, Prognosis, Peptide Fragments, medicine.anatomical_structure, Heart failure, Acute Disease, Cardiology, Cardiology and Cardiovascular Medicine, business, Biomarkers, Hormone
Abstract: Objectives This study sought to characterize urinary and plasma C-type natriuretic peptide (CNP) in acute decompensated heart failure (ADHF) to define their relationship with clinical variables and to determine whether urinary and plasma CNP together add prognostic value. Background CNP is a protective hormone that is synthesized in the kidney and endothelium and possesses antiremodeling properties. Urinary and plasma CNP levels are elevated in pathophysiological conditions; however, their regulation and prognostic value in heart failure (HF) is unclear. Methods Urinary and plasma CNP were measured in 109 healthy subjects and 208 patients with ADHF; the 95th percentile of CNP values from healthy subjects established the normal contemporary cutoffs. Patients with ADHF were stratified based on urinary and plasma CNP levels for clinical characterization and the assessment of risk for adverse outcomes. Results There was no significant correlation between urinary and plasma CNP in both cohorts. Urinary and plasma CNP were significantly elevated in patients with ADHF, and both increased with disease severity and were positively correlated with plasma N-terminal pro–B-type natriuretic peptide (NT-proBNP). Of the patients with ADHF, 23% had elevations in both urinary and plasma CNP, whereas 24% had normal CNP levels. During a median follow-up of 3 years, patients with elevated urinary and plasma CNP had a significantly higher risk of rehospitalization and/or death (HR: 1.79; P = 0.03) and rehospitalization (HR: 2.16; P = 0.01) after adjusting for age, sex, left ventricular ejection fraction, renal function, and plasma NT-proBNP. The C-statistic and integrated discrimination analyses further supported that the addition of urinary and plasma CNP to established risk models improved the prediction of adverse outcomes in patients with ADHF. Conclusions Urinary and plasma CNP are differentially regulated in ADHF, and elevations in both provided independent prognostic value for predicting adverse outcomes.
Published: 2021

35. Corona Virus Disease-19 serology, inflammatory markers, hospitalizations, case finding, and aging

Author: Latha Dulipsingh, Maxine Lang, Nathan E. Lebowitz, Lihong He, Michael L. Dansinger, Martin M. Grajower, Jessica Jimison, Margaret R. Diffenderfer, Ernst J. Schaefer, Florence Comite, Chong Yuan, Ben Saida, Andrew S. Geller, and Gary Breton
Subjects: RNA viruses, Male, Viral Diseases, Aging, Coronaviruses, Physiology, Artificial Gene Amplification and Extension, Antibodies, Viral, Gastroenterology, Biochemistry, Polymerase Chain Reaction, Immunoglobulin G, Serology, Medical Conditions, Immune Physiology, Outpatients, Medicine, Enzyme-Linked Immunoassays, Neutralizing antibody, Pathology and laboratory medicine, Virus Testing, Multidisciplinary, Immune System Proteins, biology, Age Factors, Medical microbiology, Middle Aged, Hospitalization, Infectious Diseases, C-Reactive Protein, Viruses, Female, Antibody, SARS CoV 2, Pathogens, Research Article, Adult, medicine.medical_specialty, SARS coronavirus, Patients, Science, Immunology, Research and Analysis Methods, Microbiology, Antibodies, Diagnostic Medicine, Internal medicine, Humans, Molecular Biology Techniques, Immunoassays, Molecular Biology, Aged, Medicine and health sciences, Inflammation, Inpatients, Biology and life sciences, business.industry, Interleukin-6, SARS-CoV-2, C-reactive protein, Organisms, Viral pathogens, Proteins, COVID-19, Covid 19, Odds ratio, Reverse Transcriptase-Polymerase Chain Reaction, Antibodies, Neutralizing, Microbial pathogens, Ferritin, Health Care, Immunoglobulin M, Ferritins, biology.protein, Immunologic Techniques, business
Abstract: Most deaths from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection occur in older subjects. We assessed the utility of serum inflammatory markers interleukin-6 (IL-6), C reactive protein (CRP), and ferritin (Roche, Indianapolis, IN), and SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibodies (Diazyme, Poway, CA). In controls, non-hospitalized subjects, and hospitalized subjects assessed for SARS-CoV-2 RNA (n = 278), median IgG levels in arbitrary units (AU)/mL were 0.05 in negative subjects, 14.83 in positive outpatients, and 30.61 in positive hospitalized patients (PPP = 1.00 x 10−12). Antibody or ferritin levels did not add significantly to predicting hospitalization. Antibody testing in family members and contacts of SARS-CoV-2 RNA positive cases (n = 759) was invaluable for case finding. Persistent IgM levels were associated with chronic COVID-19 symptoms. In 81,624 screened subjects, IgG levels were positive (≥1.0 AU/mL) in 5.21%, while IgM levels were positive in 2.96% of subjects. In positive subjects median IgG levels in AU/mL were 3.14 if P = 2.96 x 10−38). Our data indicate that: 1) combined IL-6 ≥10 pg/mL and CRP ≥10 mg/L identify SARS-CoV-2 positive subjects requiring hospitalization; 2) IgG levels were significantly correlated with neutralizing antibody levels with a wide range of responses; 3) IgG levels have significant utility for case finding in exposed subjects; 4) persistently elevated IgM levels are associated with chronic symptoms; and 5) IgG levels are significantly higher in positive older subjects than their younger counterparts.
Published: 2021

36. Sensory assessment of meshed skin grafts over free gracilis muscle flaps without nerve coaptation for lower extremity reconstruction

Author: Mathias Tremp, Pietro G. di Summa, Dirk J. Schaefer, Wei Wang, Yixin Zhang, Carlo M. Oranges, Daniel F. Kalbermatten, Wenjin Wang, and Natascha J. Waldkircher
Subjects: medicine.medical_specialty, lcsh:Surgery, Sensation, Muscle flap, Nerve regeneration, Patient outcome assessment, Reconstruction, Sensory system, 030230 surgery, Thermal sensation, 03 medical and health sciences, 0302 clinical medicine, medicine, Gracilis muscle, integumentary system, ddc:617, Wound dehiscence, business.industry, lcsh:RD1-811, medicine.disease, eye diseases, Surgery, surgical procedures, operative, Extremity/Lymphedema, 030220 oncology & carcinogenesis, Original Article, business
Abstract: Background Little is known about the sensate recovery of skin grafts over free non-neurotized muscle flaps. The aim of this study was to evaluate the sensitivity of free gracilis muscle flaps and meshed skin grafts without nerve coaptation. Methods Thirteen consecutive patients with a median age of 55 years (range, 21–70 years) who underwent lower extremity reconstruction between September 2014 and October 2016 were included. Complications, flap contour, skin perception, and sensate recovery were assessed. Results All flaps survived completely. In one patient, wound dehiscence and infection occurred 1 month after surgery. After a median follow-up of 14 months (range, 10–51 months), a satisfactory contour and skin perception were achieved. The Semmes-Weinstein (SW) monofilament test (154.8±22 g) and static two-point discrimination (2-PD) (12.6±0.7 mm) showed intermediate recovery compared to the surrounding site (41% and 76%, respectively). There was an intermediate correlation between flap size and sensate recovery (2-PD: r=0.27, P=0.36; SW test: r=0.45, P=0.12). Vibration sensation recovered to 60%, whereas thermal sensation remained poor (19% at 5°C and 25% at 25°C). Conclusions Finer sensation could be partially restored. However, thermal sensation remained poor.
Published: 2021

37. Effects of Immunization With the Soil-Derived Bacterium Mycobacterium vaccae on Stress Coping Behaviors and Cognitive Performance in a 'Two Hit' Stressor Model

Author: Christine L. Foxx, Jared D. Heinze, Antonio González, Fernando Vargas, Michael V. Baratta, Ahmed I. Elsayed, Jessica R. Stewart, Kelsey M. Loupy, Mathew R. Arnold, M. C. Flux, Saydie A. Sago, Philip H. Siebler, Lauren N. Milton, Margaret W. Lieb, James E. Hassell, David G. Smith, Kyo A. K. Lee, Sandra A. Appiah, Evan J. Schaefer, Morgan Panitchpakdi, Nicole C. Sikora, Kelly C. Weldon, Christopher E. Stamper, Dominic Schmidt, David A. Duggan, Yosan M. Mengesha, Mikale Ogbaselassie, Kadi T. Nguyen, Chloe A. Gates, K’loni Schnabel, Linh Tran, Joslynn D. Jones, Martha H. Vitaterna, Fred W. Turek, Monika Fleshner, Pieter C. Dorrestein, Rob Knight, Kenneth P. Wright, and Christopher A. Lowry
Subjects: 0301 basic medicine, cognition, microbiome-gut-brain axis, Physiology, medicine.medical_treatment, microbiome, stress resilience, lcsh:Physiology, Social defeat, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), microbiota, Metabolome, Medicine, Microbiome, Effects of sleep deprivation on cognitive performance, diurnal, Saline, Feces, Original Research, biology, lcsh:QP1-981, business.industry, biology.organism_classification, 030104 developmental biology, Immunization, Immunology, metabolome, Mycobacterium vaccae, business, locomotor activity, 030217 neurology & neurosurgery
Abstract: Previous studies demonstrate that Mycobacterium vaccae NCTC 11659 (M. vaccae), a soil-derived bacterium with anti-inflammatory and immunoregulatory properties, is a potentially useful countermeasure against negative outcomes to stressors. Here we used male C57BL/6NCrl mice to determine if repeated immunization with M. vaccae is an effective countermeasure in a “two hit” stress exposure model of chronic disruption of rhythms (CDR) followed by acute social defeat (SD). On day –28, mice received implants of biotelemetric recording devices to monitor 24-h rhythms of locomotor activity. Mice were subsequently treated with a heat-killed preparation of M. vaccae (0.1 mg, administered subcutaneously on days –21, –14, –7, and 27) or borate-buffered saline vehicle. Mice were then exposed to 8 consecutive weeks of either stable normal 12:12 h light:dark (LD) conditions or CDR, consisting of 12-h reversals of the LD cycle every 7 days (days 0–56). Finally, mice were exposed to either a 10-min SD or a home cage control condition on day 54. All mice were exposed to object location memory testing 24 h following SD. The gut microbiome and metabolome were assessed in fecal samples collected on days –1, 48, and 62 using 16S rRNA gene sequence and LC-MS/MS spectral data, respectively; the plasma metabolome was additionally measured on day 64. Among mice exposed to normal LD conditions, immunization with M. vaccae induced a shift toward a more proactive behavioral coping response to SD as measured by increases in scouting and avoiding an approaching male CD-1 aggressor, and decreases in submissive upright defensive postures. In the object location memory test, exposure to SD increased cognitive function in CDR mice previously immunized with M. vaccae. Immunization with M. vaccae stabilized the gut microbiome, attenuating CDR-induced reductions in alpha diversity and decreasing within-group measures of beta diversity. Immunization with M. vaccae also increased the relative abundance of 1-heptadecanoyl-sn-glycero-3-phosphocholine, a lysophospholipid, in plasma. Together, these data support the hypothesis that immunization with M. vaccae stabilizes the gut microbiome, induces a shift toward a more proactive response to stress exposure, and promotes stress resilience.
Published: 2021
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38. SARS-CoV-2 serology and virology trends in donors and recipients of convalescent plasma

Author: Steven B. Kleiboeker, Danyal Ibrahim, Ernst J. Schaefer, Mary Onoroski, Dorothy Wakefield, Patricia Nabors, Syed Altaf Hussain, Kendra Williams, Latha Dulipsingh, Lisa Cook, Jessica McKenzie, Margaret R. Diffenderfer, Colleen Lima, Rebecca Crowell, Jennifer Puff, and Reginald Eadie
Subjects: Adult, Male, Blood transfusion, medicine.medical_treatment, viruses, SARS virus, Coronavirus infections, 030204 cardiovascular system & hematology, Antibodies, Viral, Virus, Immunoglobulin G, Article, Serology, 03 medical and health sciences, Plasma, 0302 clinical medicine, COVID-19 serotherapy, Medicine, Adults, Humans, Severe acute respiratory syndrome coronavirus 2, Viral load, Viral, Antigens, Aged, Blood type, biology, business.industry, SARS-CoV-2, Immunization, Passive, COVID-19, Hematology, Middle Aged, Virology, Coronavirus, Immunoglobulin M, Severe acute respiratory syndrome, biology.protein, Female, Antibody, business, 030215 immunology
Abstract: SARS-CoV-2 has infected millions worldwide. The virus is novel, and currently there is no approved treatment. Convalescent plasma may offer a treatment option. We evaluated trends of IgM/IgG antibodies/plasma viral load in donors and recipients of convalescent plasma. 114/139 (82 %) donors had positive IgG antibodies. 46/114 donors tested positive a second time by NP swab. Among those retested, the median IgG declined (p < 0.01) between tests. 25/139 donors with confirmed SARS-CoV-2 were negative for IgG antibodies. This suggests that having had the infection does not necessarily convey immunity, or there is a short duration of immunity associated with a decline in antibodies. Plasma viral load obtained on 35/39 plasma recipients showed 22 (62.9 %) had non-detectable levels on average 14.5 days from positive test versus 6.2 days in those with detectable levels (p < 0.01). There was a relationship between IgG and viral load. IgG was higher in those with non-detectable viral loads. There was no relationship between viral load and blood type (p = 0.87) or death (0.80). Recipients with detectable viral load had lower IgG levels; there was no relationship between viral load, blood type or death.
Published: 2020
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39. The Value of Morphometric Measurements in Risk Assessment for Donor-Site Complications after Microsurgical Breast Reconstruction

Author: Elisabeth A. Kappos, Frédérique Chammartin, Daniel T. Boll, Martin Haug, Tristan M Handschin, Muriel O Meyer, and Dirk J. Schaefer
Subjects: medicine.medical_specialty, lcsh:Medicine, 030230 surgery, morphometric measurements, Article, 03 medical and health sciences, muscle-sparing transverse rectus abdominis myocutaneus flap, 0302 clinical medicine, Patient satisfaction, Quality of life, autologous reconstruction, medicine, breast reconstruction, Hernia, business.industry, lcsh:R, risk assessment, Retrospective cohort study, General Medicine, medicine.disease, deep inferior epigastric perforator flap, Surgery, 030220 oncology & carcinogenesis, donor-site complications, Risk assessment, Complication, Breast reconstruction, business, Abdominal surgery
Abstract: Microsurgical abdominally-based reconstruction is considered the gold standard in autologous breast reconstruction. Despite refined surgical procedures, donor-site complications still occur, reducing patient satisfaction and quality of life. Recent work has outlined the potential of morphometric measurements in risk assessment for postoperative hernia development. With rising demand for personalised treatment, the goal of this study was to investigate their potential in risk assessment for any donor site complication. In this retrospective cohort study, 90 patients were included who each received microsurgical breast reconstruction at the hands of one surgeon between January 2015 and May 2017. Donor-site complications formed the primary outcome and were classified according to Clavien&ndash, Dindo. Morphometric measurements were taken on a routinely performed computed tomographic angiogram. Complications occurred in 13 of the 90 (14.4%) cases studied. All patients who developed any type of postoperative donor site complication had a history of abdominal surgery. The risk of postoperative complications increased by 3% with every square centimetre of omental fat tissue (OR 1.03, 95% CI 1.00&ndash, 1.06, and p-value = 0.022). Morphometric measurements provide valuable information in risk assessment for donor-site complications in abdominally-based breast reconstruction. They may help identify personalised reconstructive options for maximal postoperative patient satisfaction and quality of life.
Published: 2020
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40. Schwann Cell-Like Cells: Origin and Usability for Repair and Regeneration of the Peripheral and Central Nervous System

Author: Alois Hopf, Dirk J. Schaefer, Daniel F. Kalbermatten, Raphael Guzman, and Srinivas Madduri
Subjects: Central Nervous System, spinal injuries, myelin regeneration, neurotrophic factors, Schwann cell-like cells, axonal regeneration, Review, Nerve Regeneration, human adipose stem cells, lcsh:Biology (General), brain injuries, Peripheral Nervous System, Humans, Schwann cells, lcsh:QH301-705.5, peripheral nerve injuries
Abstract: Functional recovery after neurotmesis, a complete transection of the nerve fiber, is often poor and requires a surgical procedure. Especially for longer gaps (>3 mm), end-to-end suturing of the proximal to the distal part is not possible, thus requiring nerve graft implantation. Artificial nerve grafts, i.e., hollow fibers, hydrogels, chitosan, collagen conduits, and decellularized scaffolds hold promise provided that these structures are populated with Schwann cells (SC) that are widely accepted to promote peripheral and spinal cord regeneration. However, these cells must be collected from the healthy peripheral nerves, resulting in significant time delay for treatment and undesired morbidities for the donors. Therefore, there is a clear need to explore the viable source of cells with a regenerative potential similar to SC. For this, we analyzed the literature for the generation of Schwann cell-like cells (SCLC) from stem cells of different origins (i.e., mesenchymal stem cells, pluripotent stem cells, and genetically programmed somatic cells) and compared their biological performance to promote axonal regeneration. Thus, the present review accounts for current developments in the field of SCLC differentiation, their applications in peripheral and central nervous system injury, and provides insights for future strategies.
Published: 2020

41. Ex-Vivo Stimulation of Adipose Stem Cells by Growth Factors and Fibrin-Hydrogel Assisted Delivery Strategies for Treating Nerve Gap-Injuries

Author: Katharina M Prautsch, Dirk J. Schaefer, Daniel F. Kalbermatten, Srinivas Madduri, Raphael Guzman, and Lucas Degrugillier
Subjects: Pathology, medicine.medical_specialty, neurotrophic factors, Bioengineering, Stimulation, lcsh:Technology, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Neurotrophic factors, growth factors, Stem cells delivery, Medicine, Schwann cells, fibrin nerve conduits, Fibrin nerve conduits, lcsh:QH301-705.5, peripheral nerve injuries, hydrogels, 030304 developmental biology, 0303 health sciences, business.industry, lcsh:T, Regeneration (biology), stem cells delivery, axonal regeneration, Hydrogels, Adipose stem cells, Vascular endothelial growth factor, adipose stem cells, Nerve growth factor, chemistry, lcsh:Biology (General), Peripheral nerve injuries, Sciatic nerve, Stem cell, Axonal regeneration, Growth factors, business, 030217 neurology & neurosurgery, Ex vivo
Abstract: Peripheral nerve injuries often result in lifelong disabilities despite advanced surgical interventions, indicating the urgent clinical need for effective therapies. In order to improve the potency of adipose-derived stem cells (ASC) for nerve regeneration, the present study focused primarily on ex-vivo stimulation of ASC by using growth factors, i.e., nerve growth factor (NGF) or vascular endothelial growth factor (VEGF) and secondly on fibrin-hydrogel nerve conduits (FNC) assisted ASC delivery strategies, i.e., intramural vs. intraluminal loading. ASC were stimulated by NGF or VEGF for 3 days and the resulting secretome was subsequently evaluated in an in vitro axonal outgrowth assay. For the animal study, a 10 mm sciatic nerve gap-injury was created in rats and reconstructed using FNC loaded with ASC. Secretome derived from NGF-stimulated ASC promoted significant axonal outgrowth from the DRG-explants in comparison to all other conditions. Thus, NGF-stimulated ASC were further investigated in animals and found to enhance early nerve regeneration as evidenced by the increased number of &beta, Tubulin III+ axons. Notably, FNC assisted intramural delivery enabled the improvement of ASC&rsquo, s therapeutic efficacy in comparison to the intraluminal delivery system. Thus, ex-vivo stimulation of ASC by NGF and FNC assisted intramural delivery may offer new options for developing effective therapies.
Published: 2020

42. eQTL discovery and their association with severe equine asthma in European Warmblood horses

Author: Molly E. McCue, Robert J. Schaefer, Vinzenz Gerber, Tosso Leeb, and Victor C. Mason
Subjects: 0301 basic medicine, Lipopolysaccharides, Candidate gene, lcsh:QH426-470, lcsh:Biotechnology, Quantitative Trait Loci, Genome-wide association study, Single-nucleotide polymorphism, 610 Medicine & health, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, lcsh:TP248.13-248.65, Genetics, Animals, GWAS, Gene Regulatory Networks, Genetic Predisposition to Disease, Horses, Gene, Regulation of gene expression, 630 Agriculture, cis eQTL, Gene Expression Profiling, Dust, Asthma, trans eQTL, Gene expression profiling, lcsh:Genetics, 030104 developmental biology, Gene Expression Regulation, RAO, Expression quantitative trait loci, PBMCs, Leukocytes, Mononuclear, 570 Life sciences, biology, 590 Animals (Zoology), Horse Diseases, Trans regulatory hotspot, Biotechnology, Genome-Wide Association Study, Research Article
Abstract: Background Severe equine asthma, also known as recurrent airway obstruction (RAO), is a debilitating, performance limiting, obstructive respiratory condition in horses that is phenotypically similar to human asthma. Past genome wide association studies (GWAS) have not discovered coding variants associated with RAO, leading to the hypothesis that causative variant(s) underlying the signals are likely non-coding, regulatory variant(s). Regions of the genome containing variants that influence the number of expressed RNA molecules are expression quantitative trait loci (eQTLs). Variation associated with RAO that also regulates a gene’s expression in a disease relevant tissue could help identify candidate genes that influence RAO if that gene’s expression is also associated with RAO disease status. Results We searched for eQTLs by analyzing peripheral blood mononuclear cells (PBMCs) from two half-sib families and one unrelated cohort of 82 European Warmblood horses that were previously treated in vitro with: no stimulation (MCK), lipopolysaccharides (LPS), recombinant cyathostomin antigen (RCA), and hay-dust extract (HDE). We identified high confidence eQTLs that did not violate linear modeling assumptions and were not significant due to single outlier individuals. We identified a mean of 4347 high confidence eQTLs in four treatments of PBMCs, and discovered two trans regulatory hotspots regulating genes involved in related biological pathways. We corroborated previous RAO associated single nucleotide polymorphisms (SNPs), and increased the resolution of past GWAS by analyzing 1,056,195 SNPs in 361 individuals. We identified four RAO-associated SNPs that only regulate gene expression of dexamethasone-induced protein (DEXI), however we found no significant association between DEXI gene expression and presence of RAO. Conclusions Thousands of genetic variants regulate gene expression in PBMCs of European Warmblood horses in cis and trans. Most high confidence eSNPs are significantly enriched near the transcription start sites of their target genes. Two trans regulatory hotspots on chromosome 11 and 13 regulate many genes involved in transmembrane cell signaling and neurological development respectively when PBMCs are treated with HDE. None of the top fifteen RAO associated SNPs strongly influence disease status through gene expression regulation. Electronic supplementary material The online version of this article (10.1186/s12864-018-4938-9) contains supplementary material, which is available to authorized users.
Published: 2018
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43. Validated low-volume aldosterone immunoassay tailored to GCLP-compliant investigations in small sample volumes

Author: Jutta Tins, B.B. Burckhardt, A. Bartel, Stephanie Laeer, and J. Schaefer
Subjects: Bioanalysis, Coefficient of variation, Clinical Biochemistry, Pharmacology, 01 natural sciences, Article, lcsh:Chemistry, Food and drug administration, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Validation, medicine, Low-volume, Good clinical laboratory practice, Aldosterone, Immunoassay, Pediatric, lcsh:R5-920, Chromatography, Pharmacodynamic, Radiological and Ultrasound Technology, medicine.diagnostic_test, 010401 analytical chemistry, Small sample, 3. Good health, 0104 chemical sciences, Low volume, lcsh:QD1-999, chemistry, 030220 oncology & carcinogenesis, lcsh:Medicine (General)
Abstract: Introduction Heart failure is well investigated in adults, but data in children is lacking. To overcome this shortage of reliable data, appropriate bioanalytical assays are required. Objectives Development and validation of a bioanalytical assay for the determination of aldosterone concentrations in small sample volumes applicable to clinical studies under Good Clinical Laboratory Practice. Methods An immunoassay was developed based on a commercially available enzyme-linked immunosorbent assay and validated according to current bioanalytical guidelines of the European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA). Results The assay (range 31.3–1000 pg/mL [86.9–2775 pmol/L]) is characterized by a between-run accuracy from − 3.8% to − 0.8% and a between-run imprecision ranging from 4.9% to 8.9% (coefficient of variation). For within-run accuracy, the relative error was between − 11.1% and + 9.0%, while within-run imprecision ranged from 1.2% to 11.8% (CV). For parallelism and dilutional linearity, the relative error of back-calculated concentrations varied from − 14.1% to + 8.4% and from − 7.4% to + 10.5%, respectively. Conclusions The immunoassay is compliant with the bioanalytical guidelines of the EMA and FDA and allows accurate and precise aldosterone determinations. As the assay can run low-volume samples of 40 μL, it is especially valuable for pediatric investigations., Highlights • Low-volume assay allowing investigations in small sample volumes. • Assay was validated according to bioanalytical guidelines of the EMA and FDA. • Assay is applied in pediatric clinical studies of the LENA project. • Obtained data is required for rational, efficient & safe drug therapy in children.
Published: 2017

44. Strengthening plastic surgery in Europe – ESPRAS survey at ESPRAS European leadership forum (ELF)

Author: Nicholas Möllhoff, Rado Zic, Dirk J. Schaefer, Dylan J. Murray, Riccardo E. Giunta, Horácio Costa, Anna Elander, Mark Henley, Giovanni Di Benedetto, Olavi Vasar, Stephan Spendel, and Cenk Demirdöver
Subjects: Gynecology, 030222 orthopedics, medicine.medical_specialty, business.industry, Mammaplasty, 030230 surgery, Europe, Leadership, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, plastic surgery, medicine, Humans, Orthopedics and Sports Medicine, Surgery, Surgery, Plastic, business
Abstract: The Executive Committee (ExCo) of the European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS) organized a first ESPRAS European Leadership Forum (ELF) to facilitate international exchange and to provide a platform for international leaders and delegates of national societies of Plastic Surgery to discuss common challenges. The presented manuscript presents key findings in a first effort of international harmonization and cooperation. Members of the executive (presidents, vice-presidents, secretary generals) and national delegates of Plastic Surgery national societies discussed hot topics in Plastic Surgery via the Zoom virtual conferencing system (Zoom Video Communications, Inc.). Attending participants responded to a virtual question answer session with questions being displayed throughout the webinar. The challenges associated with Aesthetic Surgery performed by doctors who are not board-certified Plastic Surgeons and Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) were perceived as major hot topics within most national societies. Both topics were discussed vividly. Education in plastic surgery and a European fellowship program for young Plastic Surgeons was favored by a large majority of participants. The implementation of European registries for free flaps, implants and for breast reconstruction were supported by the majority of respondents. The ESPRAS ELF provides a platform to propel international exchange and alliance, communication, education, research and future projects. A further virtual webinar with the topic "Strategies for Strengthening and Defending Plastic Surgery against Others" was suggested to be conducted in spring 2021. Das Exekutivkomitee (ExCo) der ESPRAS hat im Oktober 2020 das erste ESPRAS European Leadership Forum (ELF) initiiert, um den internationalen Austausch zwischen den verschiedenen nationalen plastisch-chirurgischen Gesellschaften zu fördern und eine Plattform für die Bewältigung gemeinsamer Herausforderung bereitzustellen. Das vorgelegte Manuskript präsentiert die wichtigsten Ergebnisse und Schlussfolgerungen dieses Treffens. Mitglieder des Vorstands (Präsidenten, Vize-Präsidenten, Generalsekretäre) und Delegierte der nationalen Gesellschaften für Plastische Chirurgie diskutierten aktuelle Themen der Plastischen Chirurgie über das virtuelle Konferenzsystem Zoom (Zoom Video Communications, Inc.). Über Zoom erfolgte zudem eine Umfrage zu verschiedenen international relevanten plastisch-chirurgischen Themen. Die Durchführung ästhetischer Eingriffe durch Ärzte ohne Facharztweiterbildung in der Plastischen Chirurgie, sowie das Brustimplantat-assoziierte anaplastische großzellige Lymphom (BIA-ALCL) wurden als die wichtigsten internationalen Herausforderungen der Plastischen Chirurgie erkannt, für deren Bewältigung auf europäischer Ebene ein standardisiertes Vorgehen diskutiert wurde. Weiterhin wurden aktuelle Entwicklungen in der Weiterbildung junger Plastischer Chirurgen eruiert, wobei die Etablierung eines europäischen Fellowship Programms von der Mehrheit der Befragten stark befürwortet wurde. Strategien zur Einführung von europäischen Registern für freie Lappenplastiken, Implantate und für die Brustrekonstruktion wurden erörtert. Das ESPRAS ELF stärkt den internationalen Austausch und die europäische Einheit in der Plastischen Chirurgie. Ein weiteres virtuelles Webinar mit dem Thema „Strategien zur Stärkung und Verteidigung der Plastischen Chirurgie gegenüber anderen“ wurde für das Frühjahr 2021 terminiert.
Published: 2020
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45. Arteriovenous loops enable free tissue transfer with otherwise inadequate local donor and recipient vessels

Author: Mathias Tremp, Henrik Eckardt, Ilario Fulco, Thomas Wolff, Carlo M. Oranges, Daniel F. Kalbermatten, Dirk J. Schaefer, and Marina Barandun
Subjects: Cancer Research, medicine.medical_specialty, Limb salvage, Free Tissue Flaps, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Reconstructive surgical procedures, medicine, Humans, Revision rate, Patient outcome assessment, Pelvis, Aged, Retrospective Studies, Pharmacology, Aged, 80 and over, Lower extremity, business.industry, Retrospective cohort study, Middle Aged, Plastic Surgery Procedures, eye diseases, Tissue transfer, Surgery, Perfusion, medicine.anatomical_structure, Treatment Outcome, Bypass surgery, Lower Extremity, 030220 oncology & carcinogenesis, Gracilis Muscle, business, Loss rate, Research Article
Abstract: Background/aim Free flap reconstruction with damaged or diseased vessels is a challenging problem. We describe our case series using an arteriovenous loop or bypass surgery with free flaps for complex defect reconstructions at the lower extremity and the pelvic region. Patients and methods In this single-center retrospective cohort study 11 consecutive patients (mean age=73 years, range=53-88 years) were operated on, between June 2016 and August 2018. Patients were reconstructed with free gracilis flaps (n=8), free latissimus dorsi flap (n=1) and chimeric scapular flap (n=1), respectively. Results The mean loop length was 30 cm (range=12-40 cm). The loop/bypass revision rate was 27% (3/11), and the overall flap loss rate was 20% (2/10). After a mean follow-up time of 17 months (range=12-24 months), the limb salvage rate was 75% (6/8). Conclusion We successfully reconstructed complex defects with poor recipient vessels using arteriovenous loops or bypass surgery and free flaps.
Published: 2020

46. A search for the standard model Higgs boson decaying to charm quarks

Author: Sirunyan, A. M. Tumasyan, A. Adam, W. Ambrogi, F. and Bergauer, T. Dragicevic, M. Eroe, J. Del Valle, A. Escalante and Flechl, M. Fruehwirth, R. Jeitler, M. Krammer, N. and Kraetschmer, I Liko, D. Madlener, T. Mikulec, I Rad, N. and Schieck, J. Schoefbeck, R. Spanring, M. Spitzbart, D. and Waltenberger, W. Wulz, C-E Zarucki, M. Drugakov, V and Mossolov, V Gonzalez, J. Suarez Darwish, M. R. De Wolf, E. A. Di Croce, D. Janssen, X. Lelek, A. Pieters, M. and Sfar, H. Rejeb Van Haevermaet, H. Van Mechelen, P. Van Putte, S. Van Remortel, N. Blekman, F. Bols, E. S. and Chhibra, S. S. D'Hondt, J. De Clercq, J. Lontkovskyi, D. and Lowette, S. Marchesini, I Moortgat, S. Python, Q. and Skovpen, K. Tavernier, S. Van Doninck, W. Van Mulders, P. and Burns, D. Beghin, D. Bilin, B. Clerbaux, B. De Lentdecker, G. Delannoy, H. Dorney, B. Favart, L. and Grebenyuk, A. Kalsi, A. K. Popov, A. Postiau, N. and Starling, E. Thomas, L. Vander Velde, C. Vanlaer, P. and Vannerom, D. Fang, W. Gao, X. Cornelis, T. Dobur, D. and Khvastunov, I Niedziela, M. Roskas, C. Tytgat, M. and Verbeke, W. Vermassen, B. Vit, M. Bondu, O. Bruno, G. and Caputo, C. David, P. Delaere, C. Delcourt, M. and Giammanco, A. Lemaitre, V Prisciandaro, J. Saggio, A. and Marono, M. Vidal Vischia, P. Zobec, J. Alves, F. L. and Alves, G. A. Correia Silva, G. Hensel, C. Moraes, A. and Rebello Teles, P. Belchior Batista das Chagas, E. Carvalho, W. and Chinellato, J. Coelho, E. Da Costa, E. M. Silveira, G. G. De Jesus Damiao, D. De Oliveira Martins, C. Fonseca De Souza, S. Huertas Guativa, L. M. Malbouisson, H. Martins, J. and Matos Figueiredo, D. Medina Jaime, M. Melo De Almeida, M. and Mora Herrera, C. Mundim, L. Nogima, H. Prado Da Silva, W. L. Sanchez Rosas, L. J. Santoro, A. Sznajder, A. and Thiel, M. Tonelli Manganote, E. J. Torres Da Silva De Araujo, F. and Vilela Pereira, A. Bernardes, C. A. Calligaris, L. and Fernandez Perez Tomei, T. R. Novaes, S. F. Padula, Sandra S. and Gregores, E. M. Mercadante, P. G. Aleksandrov, A. Antchev, G. Hadjiiska, R. Iaydjiev, P. Misheva, M. Rodozov, M. and Shopova, M. Sultanov, G. Bonchev, M. Dimitrov, A. and Ivanov, T. Litov, L. Pavlov, B. Petkov, P. Yuan, L. and Ahmad, M. Hu, Z. Wang, Y. Dozen, C. Chen, G. M. and Chen, H. S. Chen, M. Jiang, C. H. Leggat, D. Liao, H. and Liu, Z. Spiezia, A. Tao, J. Yazgan, E. Zhang, H. and Zhang, S. Zhao, J. Agapitos, A. Ban, Y. Chen, G. and Levin, A. Li, J. Li, L. Li, Q. Mao, Y. Qian, S. J. and Wang, D. Wang, Q. Xiao, M. Avila, C. Cabrera, A. and Florez, C. Gonzalez Hernandez, C. F. Segura Delgado, M. A. and Mejia Guisao, J. Ruiz Alvarez, J. D. Salazar Gonzalez, C. A. and Vanegas Arbelaez, N. Giljanovic, D. Godinovic, N. Lelas, D. and Puljak, I Sculac, T. Antunovic, Z. Kovac, M. and Brigljevic, V Ferencek, D. Kadija, K. Mesic, B. and Roguljic, M. Starodumov, A. Susa, T. Ather, M. W. and Attikis, A. Erodotou, E. Ioannou, A. Kolosova, M. and Konstantinou, S. Mavromanolakis, G. Mousa, J. Nicolaou, C. and Ptochos, F. Razis, P. A. Rykaczewski, H. Tsiakkouri, D. and Finger, M. Finger Jr, M. Jr Kveton, A. Tomsa, J. and Ayala, E. Carrera Jarrin, E. Abdalla, H. Elgammal, S. and Bhowmik, S. De Oliveira, A. Carvalho Antunes Dewanjee, R. K. and Ehataht, K. Kadastik, M. Raidal, M. Veelken, C. Eerola, P. Forthomme, L. Kirschenmann, H. Osterberg, K. and Voutilainen, M. Garcia, F. Havukainen, J. Heikkila, J. K. and Karimaki, V Kim, M. S. Kinnunen, R. Lampen, T. and Lassila-Perini, K. Laurila, S. Lehti, S. Linden, T. and Luukka, P. Maenpaa, T. Siikonen, H. Tuominen, E. and Tuominiemi, J. Tuuva, T. Besancon, M. Couderc, F. and Dejardin, M. Denegri, D. Fabbro, B. Faure, J. L. Ferri, F. Ganjour, S. Givernaud, A. Gras, P. de Monchenault, G. Hamel Jarry, P. Leloup, C. Lenzi, B. Locci, E. and Malcles, J. Rander, J. Rosowsky, A. Sahin, M. O. and Savoy-Navarro, A. Titov, M. Yu, G. B. Mijuskovic, J. and Ahuja, S. Amendola, C. Beaudette, F. Busson, P. Charlot, C. Diab, B. Falmagne, G. de Cassagnac, R. 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Shi, W. Leiton, A. G. Stahl Tu, Z. and Zhang, A. Bodek, A. de Barbaro, P. Demina, R. and Dulemba, J. L. Fallon, C. Ferbel, T. Galanti, M. and Garcia-Bellido, A. Hindrichs, O. Khukhunaishvili, A. Ranken, E. Taus, R. Chiarito, B. Chou, J. P. Gandrakota, A. and Gershtein, Y. Halkiadakis, E. Hart, A. Heindl, M. and Hughes, E. Kaplan, S. Laflotte, I Lath, A. Montalvo, R. and Nash, K. Osherson, M. Saka, H. Salur, S. Schnetzer, S. Somalwar, S. Stone, R. Thomas, S. Acharya, H. and Delannoy, A. G. Spanier, S. Bouhali, O. Dalchenko, M. De Mattia, M. Delgado, A. Eusebi, R. Gilmore, J. Huang, T. and Luo, S. Malhotra, S. Marley, D. Mueller, R. Overton, D. Pernie, L. Rathjens, D. Safonov, A. Akchurin, N. and Damgov, J. De Guio, F. Hegde, V Kunori, S. Lamichhane, K. Mengke, T. Muthumuni, S. Peltola, T. Undleeb, S. and Volobouev, I Whitbeck, A. Greene, S. Gurrola, A. Janjam, R. Johns, W. Maguire, C. Melo, A. Ni, H. Padeken, K. and Romeo, F. Sheldon, P. Tuo, S. Velkovska, J. Verweij, M. Arenton, M. W. Barria, P. Cox, B. Cummings, G. and Hakala, J. Hirosky, R. Joyce, M. Ledovskoy, A. Neu, C. and Tannenwald, B. Wolfe, E. Xia, F. Harr, R. Karchin, P. E. Poudyal, N. Sturdy, J. Thapa, P. Bose, T. and Buchanan, J. Caillol, C. Carlsmith, D. Dasu, S. De Bruyn, I Dodd, L. Galloni, C. He, H. Herndon, M. and Herve, A. Hussain, U. Lanaro, A. Loeliger, A. Long, K. and Loveless, R. Sreekala, J. Madhusudanan Pinna, D. and Ruggles, T. Savin, A. Smith, W. H. Teague, D. and Trembath-reichert, S. CMS Collaboration
Subjects: High Energy Physics::Phenomenology, High Energy Physics::Experiment
Abstract: A direct search for the standard model Higgs boson, H, produced in association with a vector boson, V (W or Z), and decaying to a charm quark pair is presented. The search uses a data set of proton-proton collisions corresponding to an integrated luminosity of 35.9 fb(-1), collected by the CMS experiment at the LHC in 2016, at a centre-of-mass energy of 13 TeV. The search is carried out in mutually exclusive channels targeting specific decays of the vector bosons: W -> l nu, Z -> ll, and Z -> nu nu, where l is an electron or a muon. To fully exploit the topology of the H boson decay, two strategies are followed. In the first one, targeting lower vector boson transverse momentum, the H boson candidate is reconstructed via two resolved jets arising from the two charm quarks from the H boson decay. A second strategy identifies the case where the two charm quark jets from the H boson decay merge to form a single jet, which generally only occurs when the vector boson has higher transverse momentum. Both strategies make use of novel methods for charm jet identification, while jet substructure techniques are also exploited to suppress the background in the merged-jet topology. The two analyses are combined to yield a 95% confidence level observed (expected) upper limit on the cross section sigma(VH) corresponding to 70 (37) times the standard model prediction.
Published: 2020

47. Catching up by hiring: The case of Huawei

Author: Kerstin J. Schaefer
Subjects: Economics and Econometrics, R&D internationalization, Strategy and Management, International business, greenfield investment, Competitive advantage, Dewey Decimal Classification::300 | Sozialwissenschaften, Soziologie, Anthropologie::330 | Wirtschaft, Management of Technology and Innovation, 0502 economics and business, ddc:330, Economics, 050207 economics, Business and International Management, latecomer companies, Telecommunications market, Industrial organization, 05 social sciences, catching up by hiring, emerging market multi-nationals, General Business, Management and Accounting, innovation capabilities, Greenfield project, Multinational corporation, Position (finance), 050203 business & management
Abstract: Hiring experts in centers of state-of-the-art technology is an important way in which a multinational enterprise (MNE) can gain competitive advantage, and yet use of this mechanism remains under-researched. This study uses the case of a Chinese MNE that recently achieved a leading position in the telecommunications market: Huawei Technologies. Taking the perspective of Huawei’s offshore hires, I find that greenfield investments contributed to overcoming liabilities of origin and outsidership in the global telecommunications industry. Nevertheless, even now that Huawei has caught up with industry incumbents, its output capabilities remain dependent on the innovation capabilities of its offshore experts.
Published: 2020
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48. VEGF Over-Expression by Engineered BMSC Accelerates Functional Perfusion, Improving Tissue Density and In-Growth in Clinical-Size Osteogenic Grafts

Author: Rene’ D. Largo, Maximilian G. Burger, Oliver Harschnitz, Conny F. Waschkies, Andrea Grosso, Celeste Scotti, Alexandre Kaempfen, Sinan Gueven, Gernot Jundt, Arnaud Scherberich, Dirk J. Schaefer, Andrea Banfi, and Nunzia Di Maggio
Subjects: 0301 basic medicine, Histology, Stromal cell, Genetic enhancement, lcsh:Biotechnology, Biomedical Engineering, Bioengineering, 02 engineering and technology, Viral vector, 03 medical and health sciences, vascularization, In vivo, lcsh:TP248.13-248.65, osteogenic grafts, medicine, Progenitor, Original Research, Chemistry, Bioengineering and Biotechnology, 021001 nanoscience & nanotechnology, VEGF, gene therapy, Panniculus carnosus, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Bone marrow, 0210 nano-technology, Perfusion, Biotechnology, bone marrow stromal cells
Abstract: The first choice for reconstruction of clinical-size bone defects consists of autologous bone flaps, which often lack the required mechanical strength and cause significant donor-site morbidity. We have previously developed biological substitutes in a rabbit model by combining bone tissue engineering and flap pre-fabrication. However, spontaneous vascularization was insufficient to ensure progenitor survival in the core of the constructs. Here, we hypothesized that increased angiogenic stimulation within constructs by exogenous VEGF can significantly accelerate early vascularization and tissue in-growth. Bone marrow stromal cells from NZW rabbits (rBMSC) were transduced with a retroviral vector to express rabbit VEGF linked to a truncated version of rabbit CD4 as a cell-surface marker. Autologous cells were seeded in clinical-size 5.5 cm3 HA scaffolds wrapped in a panniculus carnosus flap to provide an ample vascular supply, and implanted ectopically. Constructs seeded with VEGF-expressing rBMSC showed significantly increased progenitor survivival, depth of tissue ingrowth and amount of mineralized tissue. Contrast-enhanced MRI after 1 week in vivo showed significantly improved tissue perfusion in the inner layer of the grafts compared to controls. Interestingly, grafts containing VEGF-expressing rBMSC displayed a hierarchically organized functional vascular tree, composed of dense capillary networks in the inner layers connected to large-caliber feeding vessels entering the constructs at the periphery. These data constitute proof of principle that providing sustained VEGF signaling, independently of cells experiencing hypoxia, is effective to drive rapid vascularization and increase early perfusion in clinical-size osteogenic grafts, leading to improved tissue formation deeper in the constructs., Frontiers in Bioengineering and Biotechnology, 8, ISSN:2296-4185
Published: 2020

49. Search for supersymmetry in pp collisions at root s=13 TeV with 137 fb(-1) in final states with a single lepton using the sum of masses of large-radius jets

Author: Sirunyan, A. M. Tumasyan, A. Adam, W. Ambrogi, F. and Bergauer, T. Dragicevic, M. Eroe, J. Del Valle, A. Escalante and Flechl, M. Fruehwirth, R. Jeitler, M. Krammer, N. and Kraetschmer, I Liko, D. Madlener, T. Mikulec, I Rad, N. and Schieck, J. Schoefbeck, R. Spanring, M. Waltenberger, W. and Wulz, C-E Zarucki, M. Drugakov, V Mossolov, V and Gonzalez, J. Suarez Darwish, M. R. De Wolf, E. A. Di Croce, D. Janssen, X. Lelek, A. Pieters, M. Sfar, H. Rejeb and Van Haevermaet, H. Van Mechelen, P. Van Putte, S. Van Remortel, N. Blekman, F. Bols, E. S. Chhibra, S. S. and D'Hondt, J. De Clercq, J. Lontkovskyi, D. Lowette, S. and Marchesini, I Moortgat, S. Python, Q. Skovpen, K. and Tavernier, S. Van Doninck, W. Van Mulders, P. Beghin, D. and Bilin, B. Clerbaux, B. De Lentdecker, G. Delannoy, H. and Dorney, B. Favart, L. Grebenyuk, A. Kalsi, A. K. and Moureaux, L. Popov, A. Postiau, N. Starling, E. Thomas, L. Vander Velde, C. Vanlaer, P. Vannerom, D. Cornelis, T. Dobur, D. Khvastunov, I Niedziela, M. Roskas, C. and Tytgat, M. Verbeke, W. Vermassen, B. Vit, M. Bondu, O. and Bruno, G. Caputo, C. David, P. Delaere, C. Delcourt, M. Giammanco, A. Lemaitre, V Prisciandaro, J. Saggio, A. and Marono, M. Vidal Vischia, P. Zobec, J. Alves, F. L. and Alves, G. A. Correia Silva, G. Hensel, C. Moraes, A. and Rebello Teles, P. Belchior Batista Das Chagas, E. Carvalho, W. and Chinellato, J. Coelho, E. Da Costa, E. M. Da Silveira, G. G. De Jesus Damiao, D. De Oliveira Martins, C. Fonseca De Souza, S. Huertas Guativa, L. M. Malbouisson, H. Martins, J. and Matos Figueiredo, D. Medina Jaime, M. Melo De Almeida, M. and Mora Herrera, C. Mundim, L. Nogima, H. Prado Da Silva, W. L. Sanchez Rosas, L. J. Santoro, A. Sznajder, A. and Thiel, M. Tonelli Manganote, E. J. Torres Da Silva De Araujo, F. and Vilela Pereira, A. Bernardes, C. A. Calligaris, L. and Fernandez Perez Tomei, T. R. Gregores, E. M. Lemos, D. S. and Mercadante, P. G. Novaes, S. F. Padula, Sandra S. and Aleksandrov, A. Antchev, G. Hadjiiska, R. Iaydjiev, P. and Misheva, M. Rodozov, M. Shopova, M. Sultanov, G. and Bonchev, M. Dimitrov, A. Ivanov, T. Litov, L. Pavlov, B. and Petkov, P. Petrov, A. Fang, W. Gao, X. Yuan, L. and Chen, G. M. Chen, H. S. Chen, M. Jiang, C. H. Leggat, D. and Liao, H. Liu, Z. Spiezia, A. Tao, J. Yazgan, E. and Zhang, H. Zhang, S. Zhao, J. Agapitos, A. Ban, Y. and Chen, G. Levin, A. Li, J. Li, L. Li, Q. Mao, Y. and Qian, S. J. Wang, D. Wang, Q. Ahmad, M. Hu, Z. Wang, Y. Xiao, M. Avila, C. Cabrera, A. Florez, C. and Gonzalez Hernandez, C. F. Segura Delgado, M. A. Mejia Guisao, J. and Ruiz Alvarez, J. D. Salazar Gonzalez, C. A. Vanegas Arbelaez, N. Giljanovic, D. Godinovic, N. Lelas, D. and Puljak, I Sculac, T. Antunovic, Z. Kovac, M. Brigljevic, V Ferencek, D. Kadija, K. Mesic, B. Roguljic, M. and Starodumov, A. Susa, T. Ather, M. W. Attikis, A. and Erodotou, E. Ioannou, A. Kolosova, M. Konstantinou, S. and Mavromanolakis, G. Mousa, J. Nicolaou, C. Ptochos, F. and Razis, P. A. Rykaczewski, H. Tsiakkouri, D. Finger, Jr., M. and Kveton, A. Tomsa, J. Ayala, E. Carrera Jarrin, E. and Assran, Y. Elgammal, S. Bhowmik, S. De Oliveira, A. Carvalho Antunes Dewanjee, R. K. Ehataht, K. Kadastik, M. Raidal, M. Veelken, C. Eerola, P. Forthomme, L. Kirschenmann, H. and Osterberg, K. Voutilainen, M. Garcia, F. Havukainen, J. and Heikkila, J. K. Karimaki, V Kim, M. S. Kinnunen, R. and Lampen, T. Lassila-Perini, K. Laurila, S. Lehti, S. and Linden, T. Luukka, P. Maenpaa, T. Siikonen, H. Tuominen, E. Tuominiemi, J. Tuuva, T. Besancon, M. Couderc, F. and Dejardin, M. Denegri, D. Fabbro, B. Faure, J. L. Ferri, F. Ganjour, S. Givernaud, A. Gras, P. de Monchenault, G. Hamel Jarry, P. Leloup, C. Lenzi, B. Locci, E. and Malcles, J. Rander, J. Rosowsky, A. Sahin, M. O. and Savoy-Navarro, A. Titov, M. Yu, G. B. Ahuja, S. and Amendola, C. Beaudette, F. Busson, P. Charlot, C. Diab, B. Falmagne, G. de Cassagnac, R. 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Gomez Goncharov, M. Harris, P. Hsu, D. and Hu, M. Klute, M. Kovalskyi, D. Lee, Y-J Luckey, P. D. and Maier, B. Marini, A. C. Mcginn, C. Mironov, C. and Narayanan, S. Niu, X. Paus, C. Rankin, D. Roland, C. and Roland, G. Shi, Z. Stephans, G. S. F. Sumorok, K. Tatar, K. Velicanu, D. Wang, T. W. Wyslouch, B. Chatterjee, R. M. Evans, A. Guts, S. Hansen, P. Hiltbrand, J. Jain, Sh Kubota, Y. Lesko, Z. Mans, J. Revering, M. and Rusack, R. Saradhy, R. Schroeder, N. Wadud, M. A. and Acosta, J. G. Oliveros, S. Bloom, K. Claes, D. R. and Fangmeier, C. Finco, L. Golf, F. Kamalieddin, R. and Kravchenko, I Siado, J. E. Snow, G. R. Stieger, B. Tabb, W. Agarwal, G. Harrington, C. Iashvili, I. Kharchilava, A. McLean, C. Nguyen, D. Parker, A. Pekkanen, J. and Rappoccio, S. Roozbahani, B. Alverson, G. Barberis, E. and Freer, C. Haddad, Y. Hortiangtham, A. Madigan, G. and Marzocchi, B. Morse, D. M. Orimoto, T. Skinnari, L. and Tishelman-Charny, A. Wamorkar, T. Wang, B. Wisecarver, A. and Wood, D. Bueghly, J. Gilbert, A. Gunter, T. Hahn, K. A. Odell, N. Schmitt, M. H. Sung, K. Trovato, M. and Velasco, M. Bucci, R. Dev, N. Goldouzian, R. Hildreth, M. Anampa, K. Hurtado Jessop, C. Karmgard, D. J. Lannon, K. Li, W. Loukas, N. Marinelli, N. Mcalister, I and Meng, F. Musienko, Y. Ruchti, R. Siddireddy, P. Smith, G. Taroni, S. Wayne, M. Wightman, A. Wolf, M. and Woodard, A. Alimena, J. Bylsma, B. Durkin, L. S. and Francis, B. Hill, C. Ji, W. Lefeld, A. Ling, T. Y. and Winer, B. L. Dezoort, G. Elmer, P. Hardenbrook, J. and Haubrich, N. Higginbotham, S. Kalogeropoulos, A. Kwan, S. and Lange, D. Lucchini, M. T. Luo, J. Marlow, D. Mei, K. and Ojalvo, I Olsen, J. Palmer, C. Piroue, P. Stickland, D. Tully, C. Norberg, S. Barker, A. Barnes, V. E. and Chawla, R. Das, S. Gutay, L. Jones, M. Jung, A. W. and Khatiwada, A. Mahakud, B. Miller, D. H. Negro, G. and Neumeister, N. Peng, C. C. Piperov, S. Qiu, H. Schulte, J. F. Trevisani, N. Wang, F. Xiao, R. Xie, W. Cheng, T. Dolen, J. Parashar, N. Behrens, U. Dildick, S. and Ecklund, K. M. Freed, S. Geurts, F. J. M. Kilpatrick, M. and Kumar, Arun Padley, B. P. Redjimi, R. Roberts, J. Rorie, J. Shi, W. Leiton, A. G. Stahl Tu, Z. Zhang, A. and Bodek, A. de Barbaro, P. Demina, R. Dulemba, J. L. and Fallon, C. Ferbel, T. Galanti, M. Garcia-Bellido, A. and Hindrichs, O. Khukhunaishvili, A. Ranken, E. Taus, R. and Chiarito, B. Chou, J. P. Gandrakota, A. Gershtein, Y. and Halkiadakis, E. Hart, A. Heindl, M. Hughes, E. Kaplan, S. Laflotte, I Lath, A. Montalvo, R. Nash, K. and Osherson, M. Saka, H. Salur, S. Schnetzer, S. Somalwar, S. Stone, R. Thomas, S. Acharya, H. Delannoy, A. G. and Spanier, S. Bouhali, O. Dalchenko, M. De Mattia, M. and Delgado, A. Eusebi, R. Gilmore, J. Huang, T. Kamon, T. and Luo, S. Malhotra, S. Marley, D. Mueller, R. Overton, D. Pernie, L. Rathjens, D. Safonov, A. Akchurin, N. and Damgov, J. De Guio, F. Hegde, V Kunori, S. Lamichhane, K. Mengke, T. Muthumuni, S. Peltola, T. Undleeb, S. and Volobouev, I Whitbeck, A. Greene, S. Gurrola, A. Janjam, R. Johns, W. Maguire, C. Melo, A. Ni, H. Padeken, K. and Romeo, F. Sheldon, P. Tuo, S. Velkovska, J. Verweij, M. Arenton, M. W. Barria, P. Cox, B. Cummings, G. and Hakala, J. Hirosky, R. Joyce, M. Ledovskoy, A. Neu, C. and Tannenwald, B. Wolfe, E. Xia, F. Harr, R. Karchin, P. E. Poudyal, N. Sturdy, J. Thapa, P. Bose, T. and Buchanan, J. Caillol, C. Carlsmith, D. Dasu, S. De Bruyn, I Dodd, L. Galloni, C. He, H. Herndon, M. and Herve, A. Hussain, U. Lanaro, A. Loeliger, A. Long, K. and Loveless, R. Sreekala, J. Madhusudanan Mallampalli, A. and Pinna, D. Ruggles, T. Savin, A. Smith, W. H. Teague, D. and Trembath-reichert, S. CMS Collaboration
Subjects: High Energy Physics::Phenomenology, High Energy Physics::Experiment, Nuclear Experiment
Abstract: Results are reported from a search for new physics beyond the standard model in proton-proton collisions in final states with a single lepton; multiple jets, including at least one jet tagged as originating from the hadronization of a bottom quark; and large missing transverse momentum. The search uses a sample of proton-proton collision data at root s =13 TeV, corresponding to 137 fb(-1), recorded by the CMS experiment at the LHC. The signal region is divided into categories characterized by the total number of jets, the number of bottom quark jets, the missing transverse momentum, and the sum of masses of large-radius jets. The observed event yields in the signal regions are consistent with estimates of standard model backgrounds based on event yields in the control regions. The results are interpreted in the context of simplified models of supersymmetry involving gluino pair production in which each gluino decays into a top quark-antiquark pair and a stable, unobserved neutralino, which generates missing transverse momentum in the event. Scenarios with gluino masses up to about 2150 GeV are excluded at 95% confidence level (or more) for neutralino masses up to 700 GeV. The highest excluded neutralino mass is about 1250 GeV, which holds for gluino masses around 1850 GeV.
Published: 2020

50. LCAT, ApoD, and ApoA1 Expression and Review of Cholesterol Deposition in the Cornea

Author: Rhonda Flores, Janet Chang, Howard S. Kruth, David G. Cogan, Connie Zhang, Xueting Jin, and Ernst J. Schaefer
Subjects: 0301 basic medicine, Keratinocytes, Male, keratocytes, Coronary Artery Disease, 030204 cardiovascular system & hematology, Biochemistry, Phosphatidylcholine-Sterol O-Acyltransferase, 0302 clinical medicine, Lecithin Cholesterol Acyltransferase Deficiency, Cornea, RNA-Seq, Phospholipids, Tangier Disease, Corneal Dystrophies, Hereditary, medicine.diagnostic_test, Chemistry, Middle Aged, corneal stromal fibroblasts, medicine.anatomical_structure, Female, lipids (amino acids, peptides, and proteins), Lipoproteins, HDL, ApoD, Cell type, Endothelium, HDL, LCAT, In situ hybridization, Article, 03 medical and health sciences, ApoA1, Western blot, cornea, medicine, Extracellular, Humans, Molecular Biology, Apolipoproteins D, Aged, Apolipoprotein A-I, Endothelial Cells, cholesterol, Epithelial Cells, Fibroblasts, Molecular biology, Epithelium, Microscopy, Electron, 030104 developmental biology, atherosclerosis, Lipoprotein
Abstract: Lecithin:cholesterol acyltransferase (LCAT) is an enzyme secreted by the liver and circulates with high-density lipoprotein (HDL) in the blood. The enzyme esterifies plasma cholesterol and increases the capacity of HDL to carry and potentially remove cholesterol from tissues. Cholesterol accumulates within the extracellular connective tissue matrix of the cornea stroma in individuals with genetic deficiency of LCAT. LCAT can be activated by apolipoproteins (Apo) including ApoD and ApoA1. ApoA1 also mediates cellular synthesis of HDL. This study examined the expression of LCAT by epithelial cells, keratocytes, and endothelial cells, the cell types that comprise from anterior to posterior the three layers of the cornea. LCAT and ApoD were immunolocalized to all three cell types within the cornea, while ApoA1 was immunolocalized to keratocytes and endothelium but not epithelium. In situ hybridization was used to detect LCAT, ApoD, and ApoA1 mRNA to learn what cell types within the cornea synthesize these proteins. No corneal cells showed mRNA for ApoA1. Keratocytes and endothelium both showed ApoD mRNA, but epithelium did not. Epithelium and endothelium both showed LCAT mRNA, but despite the presence of LCAT protein in keratocytes, keratocytes did not show LCAT mRNA. RNA sequencing analysis of serum-cultured dedifferentiated keratocytes (commonly referred to as corneal stromal fibroblasts) revealed the presence of both LCAT and ApoD (but not ApoA1) mRNA, which was accompanied by their respective proteins detected by immunolabeling of the cultured keratocytes and Western blot analysis of keratocyte lysates. The results indicate that keratocytes in vivo show both ApoA1 and LCAT proteins, but do not synthesize these proteins. Rather, keratocytes in vivo must take up ApoA1 and LCAT from the corneal interstitial tissue fluid.
Published: 2019
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