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8. An assembly organization's approach to conducting ergonomics assessments of nutrunners in the absence of standards

Author

Mazaheri, A., Neumann, W. P., Trask, Catherine M., Mazaheri, A., Neumann, W. P., and Trask, Catherine M.

Abstract

Repetitive use of handheld nutrunners contributes to the development of musculoskeletal disorders (MSDs) among assembly operators. Tool-using organizations control the physical exposures resulting from nutrunners through their own, company-specific methods and recommendations. The aim of this study was to explore an automotive organization's current practice when conducting ergonomics assessments of nutrunner use. Fourteen employees representing different professional roles within the automotive manufacturing organization were interviewed about their involvement in, and approaches to, ergonomics evaluations of nutrunners. Findings show that the objective criteria tightening torque and tool type are combined with the operators' subjective assessments of the load to identify MSD risks associated with nutrunner use. This way, the effects of factors such as working posture could be integrated into the assessment. Further, it was found that information and knowledge availability could influence the resulting exposures estimates, where for example information about how to appropriately select tool settings is not readily available. In addition, there are negotiating criteria such as quality considerations which need to be balanced with health and safety management, influencing the physical demands associated with power tools. Relevance to industry: By providing insight into an automotive manufacturer's approach to managing and assessing handheld tightening tools, policy-makers can form recommended limits and methods for standardized assessments of reaction load exposure from nutrunners., QC 20240619

Published
2024
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11. Commentary on the Past, Present, and Future of Nursing Workload Research.

Author

MacPhee, Maura, Havaei, Farinaz, Bookey-Bassett, Sue, Neumann, W Patrick, Qureshi, Sadeem Munawar, Greig, Michael A, and Keselman, David

Subjects
NURSE supply & demand, PSYCHOLOGICAL burnout, HOSPITAL nursing staff, LABOR turnover, WORK environment, SYSTEMS design, SIMULATION methods in education, EXPERIMENTAL design, NURSING research, EMPLOYEES' workload
Abstract

The aim of this paper is to enhance readers' understanding of research design strategies, past and present, for studying nursing workloads. Future research directions are also discussed. Nursing workloads are associated with nurse burnout and turnover. During our current global nursing shortage, researchers must identify ways to mitigate nurses' heavy workloads. Relevant, prior nursing workload research is presented with brief descriptions of designs, methods and findings. To illustrate the current complexity of nurses' work environments and the myriad factors that influence nurses' workloads, this paper features the ongoing nursing workload research of two Canadian research teams with different methodological approaches. These two teams are employing current research innovations, such as human factors multi-systems frameworks, design thinking, simulation modeling and integrated knowledge translation. With respect to future research implications, the teams are melding methods and tools to promote a more sophisticated way of understanding the complex linkages between patient needs, systems design and the management of nurses' workloads. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Is there a u-shaped relationship between load levels and fatigue and recovery? : An examination of possible mechanisms

Author

Yung, Marcus, Rose, Linda, Neumann, W. Patrick, Yazdani, Amin, Kapellusch, Jay, Yung, Marcus, Rose, Linda, Neumann, W. Patrick, Yazdani, Amin, and Kapellusch, Jay

Abstract

In a previous study, an unexpected u-shaped relationship was observed between load level andfatigue/recovery responses. Moderate load levels resulted in lower perceived discomfort, pain,and fatigue, and shorter recovery times compared to either low or high load levels. Thisphenomenon has been reported in other studies, but no article has examined the possiblemechanisms that might explain this u-shaped relationship. In this paper, we re-examined thepreviously published data and found that the phenomenon does not appear to be due to theexperimental artefact; the u-shape may be due to unexpectedly lower fatigue effects at moderateloads, and higher fatigue effects at lower loads. We then conducted a literature review andidentified several possible physiological, perceptual, and biomechanical explanatory mechanisms.No single mechanism explains the entirety of the phenomenon. Further research is needed onthe relationship between work exposures, fatigue, and recovery, and the mechanisms related tothe u-shaped relationship. Practitioner summary: We examine a previously observed u-shaped relationship between loadlevel and fatigue/recovery, where moderate force resulted in lower perceived fatigue andshorter recovery times. A u-shaped fatigue response suggests that simply minimising load levelsmight not be an optimal approach to reduce the risk of workplace injuries., QC 20230619

Published
2023
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16. Investigating the productivity in different assembly system configurations for a better inclusion of disabled workers

Author

Finco, Serena, Neumann, W. Patrick, and Setayesh, Azin

Abstract

One of the United Nations’ Sustainable Development Goals is focused on decent work and growth which aims to reduce and, finally, remove all barriers for people with a form of diversity like disability. In such a context, manufacturing and production systems should be adapted by adopting specific equipment to help workers with disability while executing jobs according to the type of disability they report. Jobs must be properly planned since disabled workers have physical or cognitive disabilities and specific rights to work. Further, aiming to guarantee a real inclusion of workers with disability production systems should be designed to include these workers in the same working environment as workers without disability. This paper focuses on assembly systems, and it aims to investigate how different designs could impact both the productivity and inclusion of disabled workers. Then, due to the higher variety of products belonging to the same family mixed model assembly systems are considered. For each assembly system design, the daily productivity is calculated by using a simulation approach. Finally, according to the obtained results we provide some considerations about the convenience of adopting parallel flows to guarantee higher inclusion without affecting too much the productivity of the assembly system.

Published
2024
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31. Images from the surface of asteroid Ryugu show rocks similar to carbonaceous chondrite meteorites

Author

Jaumann, R., Schmitz, N., Ho, T. -M., Schroder, S. E., Otto, K. A., Stephan, K., Elgner, S., Krohn, K., Preusker, F., Scholten, F., Biele, J., Ulamec, S., Krause, C., Sugita, Seiji, Matz, K. -D., Roatsch, T., Parekh, R., Mottola, S., Grott, M., Michel, P., Trauthan, F., Koncz, A., Michaelis, H., Lange, C., Grundmann, J. T., Maibaum, M., Sasaki, K., Wolff, F., Reill, J., Moussi-Soffys, A., Lorda, L., Neumann, W., Vincent, J. -B., Wagner, R., Bibring, J. -P., Rauer, H., Kameda, Shingo, Yano, Hajime, Watanabe, Sei-ichiro, Yoshikawa, Makoto, Tsuda, Yuichi, Okada, Tatsuaki, Yoshimitsu, Tetsuo, Mimasu, Yuya, Saiki, Takanao, Yabuta, Hikaru, Honda, Rie, Morota, Tomokatsu, Yokota, Yasuhiro, Kouyama, Toru, DLR Institute of Planetary Research, German Aerospace Center (DLR), DLR Institut für Planetenforschung, Deutsches Zentrum für Luft- und Raumfahrt [Berlin] (DLR), University of Potsdam, Joseph Louis LAGRANGE (LAGRANGE), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), University of São Paulo (USP), Institut d'astrophysique spatiale (IAS), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Hiroshima University, and ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015)

Subjects
Surface (mathematics), Multidisciplinary, 010504 meteorology & atmospheric sciences, [SDU.ASTR]Sciences of the Universe [physics]/Astrophysics [astro-ph], MASCOT, [SDU.ASTR.EP]Sciences of the Universe [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], carbonaceous chondrites, Hayabusa-2, 01 natural sciences, Asteroids, Astrobiology, Matrix (geology), images, Meteorite, Asteroid, [SDU]Sciences of the Universe [physics], Carbonaceous chondrite, 0103 physical sciences, Ryugu, Formation and evolution of the Solar System, 010303 astronomy & astrophysics, Geology, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences
Abstract

著者人数: 50名, 資料番号: SA1190102000

Published
2019

35. Science Motivations for the Future Exploration of Ceres

Author

Castillo-Rogez, Julie, Scully, Jennifer, Neveu, Marc, Wyrick, Danielle, Thangjam, Guneshwar, Rivkin, Andrew, Sori, Michael, Vinogradoff, Vassilissa, Miller, Kelly, Ermakov, Anon, Hughson, Kynan, Quick, Lynnae, Nathues, Andreas, Sanctis, Maria Cristina De, Ermakov, Anton, De Sanctis, Maria, Ahrens, C, Beck, P, Bland, P, Bose, M, Buczkowski, D, Combe, J.-P, Daly, T, Desch, S, Espley, J, Fries, M, Friesen, S, Glein, C, Hodyss, R, House, C, Jaumann, R, Kite, E, Krohn, K, Landis, M, Li, J.-Y, Mcadam, A, Marchi, S, Meech, K, Melwani Daswani, M, Mccord, T, Neumann, W, O'Brien, D, Otto, K, Palomba, E, Parekh, R, Raymond, C, Roatsch, T, Ruesch, O, Russell, C, Sarid, G, Schmitz, N, Sizemore, H, Stein, N, Stephan, K, Tosi, F, Vernazza, P, Villarreal, M, Williams, D, Yano, H, Zambon, F, Zolensky, M, Mcsween, H, Shi, X, Ip, W.-H, Lucchetti, A, Pajola, Maurizio, Santos-Sanz, P, Ulamec, S, De Léon, J, Barucci, A, Henderson, B, Kaplan, H, Hofmann, A, Ciarniello, M, Neesemann, A, Raponi, A, Jha, D, Graps, A, Formisano, M, Schenk, P, Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), NASA Goddard Institute for Space Studies (GISS), NASA Goddard Space Flight Center (GSFC), Physique des interactions ioniques et moléculaires (PIIM), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDU]Sciences of the Universe [physics], Environmental science, 010501 environmental sciences, 010502 geochemistry & geophysics, 01 natural sciences, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences
Abstract

International audience

Published
2021

37. A Staggered Seat is Beneficial for the Flying V Aircraft

Author

Vink, P., Anjani, S., Percuoco, C., Vos, Roelof, Vanacore, Amalia, Black, Nancy L., Neumann, W. Patrick, Noy, Ian, Black N.L., Neumann W.P., Noy I., Vink, P., Anjani, S., Percuoco, C., Vos, R., and Vanacore, A.

Subjects
Aircraft seat, Flying V, Legroom, Armrest, Comfort, Staggered, business.product_category, Aeronautics, Computer science, Staggered, Aircraft seat, Flying V, Arm Rest, business, Longitudinal axis, Leg room, Comfort, Airplane
Abstract

Staggered seats might be a solution for a V-shaped aircraft (the Fly-ing V). The cabin longitudinal axis of this airplane has a 26 degrees angle with respect to the direction of flight. When seats are positioned in the direction of flight, they consequently have an angle to the cabin and become staggered. It is unknown whether the comfort of this staggered seat is appreciated. In this study, 117 participants tested the comfort and the privacy experience in this staggered seat compared with a regular aircraft seat. The experiment showed that both comfort and privacy were significantly better in the staggered seats. However, the analysis is based on short-term evaluations, which means that long-term effects still need to be studied and also the effects of groups travel-ling together need to be investigated.

Published
2021

39. Exploiting Forward-Looking Data in Prospective Ergonomics: The Case of Aviation

Author

Black, Nancy L., Neumann, W. Patrick, Noy, Ian, Ung, Karine, Doyon-Poulin, Philippe, Robert, Jean-Marc, Black, Nancy L., Neumann, W. Patrick, Noy, Ian, Ung, Karine, Doyon-Poulin, Philippe, and Robert, Jean-Marc

Abstract

In this study, we investigated different sources of forward-looking data in the domain of aviation and pilot training that are of interest to human factors researchers and practitioners involved in the creation of future artefacts. We show how trends that are emerging for the future as well as unforeseen short-term events, such as the COVID-19 pandemic, impact decisions made on the design of future artefacts in aviation. In this respect, the case of anticipating pilot shortage is examined in relation with the design of a new form of training program: evidence-based training (EBT).

Published
2021

40. Goal-Directed Task Analysis for Situation Awareness Requirements During Ship Docking in Compulsory Pilotage Area

Author

Black, Nancy L., Neumann, W. Patrick, Noy, Ian, Haffaci, Karima, Massicotte, Mia-Claude, Doyon-Poulin, Philippe, Black, Nancy L., Neumann, W. Patrick, Noy, Ian, Haffaci, Karima, Massicotte, Mia-Claude, and Doyon-Poulin, Philippe

Abstract

In this paper we present the results from a Goal Directed Task Anal-ysis (GDTA), a variant of cognitive task analysis techniques, to extract the op-erator's situation awareness requirements. This analysis is done with 8 pilots from the Mid Saint-Laurence Pilots Corporation (CPSLC) on a ship docking scenario in a compulsory pilotage area. These findings are used to develop a tool to measure the pilot's situation awareness during the maneuver using SAGAT questionnaire.

Published
2021

41. Remote Design of a Pediatric Intensive Care Unit Dashboard in Time of Pandemics

Author

Black, Nancy L., Neumann, W. Patrick, Noy, Ian, Hébert-Lavoie, Maxence, Ung, Karine, Boudreault, Lise, Mahmoudi, Célia, Vu, Quynh Phuong, Jouvet, Philippe, Doyon-Poulin, Philippe, Black, Nancy L., Neumann, W. Patrick, Noy, Ian, Hébert-Lavoie, Maxence, Ung, Karine, Boudreault, Lise, Mahmoudi, Célia, Vu, Quynh Phuong, Jouvet, Philippe, and Doyon-Poulin, Philippe

Abstract

To support the pediatric intensive care unit with the COVID-19 pandemic, we followed a user-centered design process to create a dashboard in a context where direct access to users was impossible. To this end, we applied contextual inquiry, user interview, requirement definition, iterative design with user validation and usability testing in a remote fashion. Being unable to be physically present at the hospital limited our understanding of the context of use, extended the duration of the study and limited the number of interviews and testing sessions. However, we were able to benefit from the experience of our team members, adopt an efficient decision-making method to select appropriate requirements and use remote moderated usability testing to conform our design process to an aggressive timeline.

Published
2021

43. Neuromodulation effects of deep brain stimulation on beta rhythm: A longitudinal local field potential study.

Author

Chen, Y, Gong, C, Tian, Y, Orlov, N, Zhang, J, Guo, Y, Xu, S, Jiang, C, Hao, H, Neumann, W-J, Kühn, AA, Liu, H, Li, L, Chen, Y, Gong, C, Tian, Y, Orlov, N, Zhang, J, Guo, Y, Xu, S, Jiang, C, Hao, H, Neumann, W-J, Kühn, AA, Liu, H, and Li, L

Abstract

BACKGROUND: Deep brain stimulation (DBS) holds great promise in treating various brain diseases but its chronic therapeutic mechanisms are unclear. OBJECTIVE: To explore the immediate and chronic effects of DBS on brain oscillations, and understand how different sub-bands of oscillations may be related to symptom improvement in Parkinson's patients. METHODS: We carried out a longitudinal study to examine the effects of DBS on local field potentials recorded by sensing-enabled neurostimulators in the subthalamic nuclei of Parkinson's patients, using a novel block-design stimulation paradigm. RESULTS: DBS significantly suppressed beta activity (13-35Hz) but the suppression effect appeared to gradually attenuate during a 6-month follow-up period after surgery (p = 0.002). However, beta suppression did not attenuate after repeated stimulation over several minutes (p > 0.110), suggesting that the changes in beta suppression may reflect a slow reconfiguration of neural pathways instead of habituation. Suppression of beta was also associated with clinical symptom improvement across subjects. Importantly, symptom-relevant features fell within the high beta band at month 1 but shifted to the low beta band at month 6, indicating that the high beta and the low beta oscillations may play different functional roles and respond differently to stimulation over the long-term treatment. CONCLUSION: These data may advance understanding of chronic DBS effects on beta oscillations and their association with clinical improvement, offering novel insights to the therapeutic mechanisms of DBS.

Published
2020

44. A comparison of work-rest models using a 'breakpoint' analysis raises questions

Author

Neumann, W. Patrick, Motiwala, Mufaddal, Rose, Linda, Neumann, W. Patrick, Motiwala, Mufaddal, and Rose, Linda

Abstract

OCCUPATIONAL APPLICATIONS Designing sustainable cyclic work requires attention to both the workload amplitude as well as the duty cycle, the fraction of the work cycle with active workload, that therefore also defines the recovery phase of the cycle. A number of different approaches and models have been developed to calculate the required recovery time for a given load and duty cycle. We present a comparison of three types of models at the "breakpoint" that defines the boundary of load amplitude and duty cycle where fatigue begins to accumulate faster than recovery allows within the work cycle. This comparison shows considerable variation between models of the "allowable" load or duty cycle depending on the method used. Practitioners should thus be cautious applying these models indiscriminately in job design as their results can vary substantially. In particular, differences between the tasks used for model formulation and application may compromise validity, and model application in a given context should be verified before broad application. TECHNICAL ABSTRACT Rationale: There is a need for tools to help design sustainable work in which muscular capacity and other human resources can recover at least as quickly as they are used. Purpose: In this brief report, three different approaches presented in the literature to determining work-rest schedules in cyclic work are compared. Methods: First, a set of five different muscular endurance models coupled with a recovery time model were considered, both with and without a dynamic work correction factor. Second, we examined a model of "resumption time", and third a psychophysically-based model of maximum duty cycle was included. These models were compared using the concept of a "breakpoint" in fatigue accumulation-the point at which a given load amplitude and duty cycle combination begins to cause accumulation of fatigue in each cycle and from which there is inadequate time to recover. Results: While the five endurance t, QC 20210923

Published
2020
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45. Carboranyl Derivatives of Rofecoxib with Cytostatic Activity Against Human Melanoma and Colon Cancer Cells

Author

Buzharevski, A., Paskas, S., Sárosi, M.-B., (0000-0003-4916-3794) Laube, M., Lönnecke, P., Neumann, W., Murganić, B., Mijatović, S., Maksimović-Ivanić, D., (0000-0002-1610-1493) Pietzsch, J., Hey-Hawkins, E., Buzharevski, A., Paskas, S., Sárosi, M.-B., (0000-0003-4916-3794) Laube, M., Lönnecke, P., Neumann, W., Murganić, B., Mijatović, S., Maksimović-Ivanić, D., (0000-0002-1610-1493) Pietzsch, J., and Hey-Hawkins, E.

Abstract

Due to the involvement of cyclooxygenase-2 (COX-2) in carcinogenesis, COX-2-selective inhibitors are increasingly studied for their potential cytotoxic properties. Moreover, the incorporation of carboranes in structures of established anti-inflammatory drugs can improve the potency and metabolic stability of the inhibitors. Herein, we report the synthesis of carborane-containing derivatives of rofecoxib that display remarkable cytostatic activity in the micromolar range with excellent selectivity for melanoma and colon cancer cell lines over normal cells. Furthermore, it was shown that the carborane-modified derivatives of rofecoxib displayed different modes of action that was dependent on the cell type.

Published
2020

47. Search for charginos, neutralinos and gravitinos at LEP

Author

Abreu, P., Adam, W., Adye, T., Ajinenko, I., Alekseev, G. D., Alemany, R., Allport, P. P., Almehed, S., Amaldi, U., Amato, S., Andersson, P., Andreazza, A., Antilogus, P., Apel, W -D., Arnoud, Y., Åsman, B., Augustin, J -E., Augustinus, A., Baillon, P., Bambade, P., Barbi, M., Bardin, D. Y., Barker, G., Baroncelli, A., Barring, O., Bates, M. J., Battaglia, M., Baubillier, M., Baudot, J., Becks, K -H., Begalli, M., Beilliere, P., Belokopytov, Yu., Belous, K., Benvenuti, A. C., Berat, C., Berggren, M., Bertini, D., Bertrand, D., Besancon, M., Bianchi, F., Bigi, M., Bilenky, M. S., Billoir, P., Bizouard, M -A., Bloch, D., Blume, M., Bonesini, M., Bonivento, W., Boonekamp, M., Booth, P. S. L., Borgland, A. W., Borisov, G., Bosio, C., Botner, O., Boudinov, E., Bouquet, B., Bourdarios, C., Bowcock, T. J. V., Bozzo, M., Branchini, P., Brand, K. D., Brenke, T., Brenner, R. A., Brown, R. C. A., Bruckman, P., Brunet, J -M., Bugge, L., Buran, T., Burgsmueller, T., Buschmann, P., Cabrera, S., Caccia, M., Calvi, M., Camacho Rozas, A. J., Camporesi, T., Canale, V., Canepa, M., Carena, F., Carroll, L., Caso, C., Castillo Gimenez, M. V., Cattai, A., Cavallo, F. R., Chabaud, V., Chapkin, M., Charpentier, Ph., Chaussard, L., Checchia, P., Chelkov, G. A., Chen, M., Chierici, R., Chhapnikov, P., Chochula, P., Chorowicz, V., Chudoba, J., Cindro, V., Collins, P., Colomer, M., Contri, R., Cortina, E., Cosme, G., Cossutti, F., Cowell, J -H., Crawley, H. B., Crennell, D., Crosetti, G., Cuevas Maestro, J., Czellar, S., Dahm, J., Dalmagne, B., Damgaard, G., Dauncey, P. D., Davenport, M., Da Silva, W., Deghorain, A., Della Ricca, G., Delpierre, P., Demaria, N., De Angelis, A., De Boer, W., De Brabandere, S., De Clercq, C., De La Vaissiere, C., De Lotto, B., De Min, A., De Paula, L., Dijkstra, H., Di Ciaccio, L., Di Diodato, A., Djannati, A., Dolbeau, J., Doroba, K., Dracos, M., Drees, J., Drees, K. -A., Dris, M., Durand, J -D., Edsall, D., Ehret, R., Eigen, G., Ekelof, T., Ekspong, G., Elsing, M., Engel, J -P., Erzen, B., Espirito Santo, M., Falk, E., Fanourakis, G., Fassouliotis, D., Feindt, M., Fenyuk, A., Ferrari, P., Ferrer, A., Fichet, S., Filippas, T. A., Firestone, A., Fischer, P. -A., Foeth, H., Fokitis, E., Fontanelli, F., Formenti, F., Franek, B., Frodesen, A. G., Fruhwirth, R., Fulda-Quenzer, F., Fuster, J., Galloni, A., Gamba, D., Gandelman, M., Garcia, C., Garcia, J., Gaspar, C., Gasparini, U., Gavillet, Ph., Gazis, E. N., Gele, D., Gerber, J -P., Gokieli, R., Golob, B., Goncalves, P., Gopal, G., Gorn, L., Gorski, M., Gouz, Yu., Gracco, V., Graziani, E., Green, C., Grefrath, A., Gris, P., Grosdidier, G., Grzelak, K., Gumenyuk, S., Gunther, M., Guy, J., Hahn, F., Hahn, S., Hajduk, Z., Hallgren, A., Hamacher, K., Harris, F. J., Hedberg, V., Henriques, R., Hernandez, J. J., Herquet, P., Herr, H., Hessing, T. L., Heuser, J. -M., Higon, E., Holmgren, S -O., Holt, P. J., Holthuizen, D., Hoorelbeke, S., Houlden, M., Hrubec, J., Huet, K., Hultqvist, K., Jackson, J. N., Jacobsson, R., Jalocha, P., Janik, R., Jarlskog, Ch., Jarlskog, G., Jarry, P., Jean-Mariels, B., Johansson, E. K., Jonsson, L., Jonsson, P., Joram, C., Juillot, P., Kaiser, M., Kapusta, F., Karafasoulis, K., Karvelas, E., Katsanevas, S., Katsoufis, E. C., Keranen, R., Khokhlov, Yu., Khomenko, B. A., Khovanski, N. N., King, B., Kjaer, N. J., Klapp, O., Klein, H., Kluit, P., Knoblauch, D., Kokkinias, P., Koratzinos, M., Korcyl, K., Kostioukhine, V., Kourkoumelis, C., Kouznetsov, O., Krammer, M., Kreuter, C., Kronkvist, I., Krstic, J., Krumstein, Z., Krupinski, W., Kubinec, P., Kucewicz, W., Kurvinen, K., Lacasta, C., Laktineh, I., Lamsa, J. W., Lanceri, L., Lane, D. W., Langefeld, P., Lapin, V., Laugier, J -P., Lauhakangas, R., Leder, G., Ledroit, F., Lefebure, V., Legan, C. K., Leisos, A., Leitner, R., Lemonne, J., Lenzen, G., Lepeltier, V., Lesiak, T., Lethuillier, M., Libby, J., Liko, D., Lipniacka, A., Lippi, I., Loerstad, B., Loken, J. G., Lopez, J. M., Loukas, D., Lutz, P., Lyons, L., MacNaughton, J., Maehlum, G., Mahon, J. R., Maio, A., Malmgren, T. G. M., Malychev, V., Mandl, F., Marco, J., Marco, R., Marechal, B., Margoni, M., Marin, J -C., Mariotti, C., Markou, A., Martinez-Rivero, C., Martinez-Vidal, F., Marti i Garcia, S., Masik, J., Matorras, F., Matteuzzi, C., Matthiae, G., Mazzucato, M., Mc Cubbin, M., Mc Kay, R., Mc Nulty, R., Mc Pherson, G., Medbo, J., Meroni, C., Meyer, S., Meyer, W. T., Michelotto, M., Migliore, E., Mirabito, L., Mjoernmark, U., Moa, T., Moeller, R., Moenig, K., Monge, M. R., Morettini, P., Mueller, H., Muenich, K., Mulders, M., Mundim, L. M., Murray, W. J., Muryn, B., Myatt, G., Myklebust, T., Naraghi, F., Navarria, F. L., Navas, S., Nawrocki, K., Negri, P., Nemecek, S., Neumann, W., Neumeister, N., Nicolaidou, R., Nielsen, B. S., Nieuwenhuizen, M., Nikolaenko, V., Nikolenko, M., Niss, P., Nomerotski, A., Normand, A., Nygren, A., Oberschulte-Beckmann, W., Obraztsov, V., Olshevski, A. G., Onofre, A., Orava, R., Orazi, G., Ortuno, S., Osterberg, K., Ouraou, A., Paganini, P., Paganoni, M., Paiano, S., Pain, R., Palka, H., Papadopoulou, Th. D., Papageorgiou, K., Pape, L., Parkes, C., Parodi, F., Parzefall, U., Passeri, A., Pegoraro, M., Peralta, L., Pernegger, H., Pernicka, M., Perrotta, A., Petridou, C., Petrolini, A., Phillips, H. T., Piana, G., Pierre, F., Pimenta, M., Piotto, E., Podobnik, T., Podobrin, O., Pol, M. E., Polok, G., Poropat, P., Pozdniakov, V., Privitera, P., Pukhaeva, N., Pullia, A., Radojicic, D., Ragazzi, S., Rahmani, H., Ratoff, P. N., Read, A. L., Reale, M., Rebecchi, P., Redaelli, N. G., Regler, M., Reid, D., Reinhardt, R., Renton, R. B., Resvanis, L. K., Richard, F., Ridky, J., Rinaudo, G., Rohne, O., Romero, A., Ronchese, P., Roos, L., Rosenberg, E. 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Published
1998
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48. Beta bursts during continuous movements accompany the velocity decrement in Parkinson's disease patients

Author

Lofredi, R, Tan, H, Neumann, W, Yeh, C, Schneider, G, Kühn, A, and Brown, P

Subjects
Male, Bradykinesia, Deep Brain Stimulation, Movement, Parkinson's disease, Parkinson Disease, Hypokinesia, Middle Aged, Subthalamic nucleus, Article, lcsh:RC321-571, Humans, Beta bursts, Female, Beta Rhythm, Beta oscillations, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Aged
Abstract

Bradykinesia is reported to correlate with subthalamic beta power (13-35 Hz) recorded at rest in Parkinson's disease (PD). Pilot studies suggest adaptive deep brain stimulation triggered by amplitude threshold crossings of beta activity defined at rest is effective. This is puzzling, given that beta is suppressed during repetitive movements when bradykinesia becomes apparent. Recently, increased beta power in PD has been linked to beta bursts. Here we investigate whether beta bursts also occur during repetitive movements and relate to progressive decrement in movement velocity. Therefore, subthalamic local field potentials were recorded in 12 PD patients off medication while performing 30s blocks of rotatory movements alternating with rest periods. Bursts were defined separately for the low (13-20 Hz) and high (20-35 Hz) beta band using thresholds defined at rest. As expected, velocity significantly decreased within movement blocks. Despite the sustained suppression of both beta sub-bands, bursts could still be detected during movement. Beta bursts were reduced in amplitude, duration and rate during movement with beta rate correlating best with beta power. A mixed-effects linear model revealed that percentage time spent in beta bursts predicted velocity decreases better than averaged power. This correlation was specific for the low beta band. Our results link beta bursts during movement to bradykinesia. This helps explain how beta activity may contribute to bradykinetic movement decrement even though mean beta power is reduced during movement. Moreover, our findings help explain the effectiveness of adaptive DBS triggered off beta bursts, even though these may be defined with respect to beta levels at rest.

Published
2019

49. Studies towards the development of a PET radiotracer for imaging of the P2Y1 receptors in the brain: synthesis, 18F-labeling and preliminary biological evaluation

Author

Moldovan, R.-P., Wenzel, B., Teodoro, R., Neumann, W., Dukic-Stefanovic, S., Deuther-Conrad, W., Hey-Hawkins, E., Krügel, U., and Brust, P.

Subjects
Positron emission tomography, Purine P2Y1 receptors, Hydrophilic interaction chromatography, Micellar chromatography, Radiometabolites, Brain PET tracers
Abstract

Purine nucleotides such as ATP and ADP are important extracellular signaling molecules in almost all tissues activating various subtypes of purinoreceptors. In the brain, the P2Y1 receptor (P2Y1R) subtype mediates trophic functions like differentiation and proliferation, and modulates fast synaptic transmission, both suggested to be affected in diseases of the central nervous system. Research on P2Y1R is limited because suitable brain-penetrating P2Y1R-selective tracers are not yet available. Here, we describe the first efforts to develop an 18F-labeled PET tracer based on the structure of the highly affine and selective, non-nucleotidic P2Y1R allosteric modulator 1-(2-[2-(tert-butyl)phenoxy]pyridin-3-yl)-3-[4-(trifluoromethoxy)phenyl]urea (7). A small series of fluorinated compounds was developed by systematic modification of the p-(trifluoromethoxy)phenyl, the urea and the 2-pyridyl subunits of the lead compound 7. Additionally, the p-(trifluoromethoxy)phenyl subunit was substituted by carborane, a boron-rich cluster with potential applicability in boron neutron capture therapy (BNCT). By functional assays, the new fluorinated derivative 1-{2-[2-(tert-butyl)phenoxy]pyridin-3-yl}-3-[4-(2-fluoroethyl)phenyl]urea (18) was identified with a high P2Y1R antagonistic potency (IC50 = 10 nM). Compound [18F]18 was radiosynthesized by using tetra-n-butyl ammonium [18F]fluoride with high radiochemical purity, radiochemical yield and molar activities. Investigation of brain homogenates using hydrophilic interaction chromatography (HILIC) revealed [18F]fluoride as major radiometabolite. Although [18F]18 showed fast in vivo metabolization, the high potency and unique allosteric binding mode makes this class of compounds interesting for further optimizations and investigation of the theranostic potential as PET tracer and BNCT agent.

Published
2019

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