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871 results on '"Schafer M."'

2. A block-coupled Finite Volume methodology for problems of large strain and large displacement

Author

Azevedo, L. R., Cardiff, P., Galindo-Rosales, F. J., and Schafer, M.

Subjects
Computer Science - Computational Engineering, Finance, and Science
Abstract

A nonlinear block-coupled Finite Volume methodology is developed for large displacement and large strain regime. The new methodology uses the same normal and tangential face derivative discretisations found in the original fully coupled cell-centred Finite Volume solution methodology for linear elasticity, meaning that existing block-coupled implementations may easily be extended to include finite strains. Details are given of the novel approach, including use of the Newton-Raphson procedure on a residual functional defined using the linear momentum equation. A number of 2-D benchmark cases have shown that, compared with a segregated procedure, the new approach exhibits errors with many orders of magnitude smaller and a much higher convergence rate.

Published
2020

3. Discovery of the first orally bioavailable ADAMTS7 inhibitor BAY-9835

Author

Schafer, M., primary, Meibom, D., additional, Wasnaire, P., additional, Beyer, K., additional, Broehl, A., additional, Cancho-Grande, Y., additional, Elowe, N., additional, Henninger, K., additional, Johannes, S., additional, Jungmann, N., additional, Krainz, T., additional, Lindner, N., additional, Maassen, S., additional, MacDonald, B., additional, Menshykau, D., additional, Mittendorf, J., additional, Sanchez, G., additional, Stefan, E., additional, Torge, A., additional, Xing, Y., additional, and Zubov, D., additional

Published
2024
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4. Extraction of many-body configurations from nonlinear absorption in semiconductor quantum wells

Author

Smith, R. P., Wahlstrand, J. K., Funk, A. C., Mirin, R. P., Cundiff, S. T., Steiner, J. T., Schafer, M., Kira, M., and Koch, S. W.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Condensed Matter - Other Condensed Matter
Abstract

Detailed electronic many-body configurations are extracted from quantitatively measured timeresolved nonlinear absorption spectra of resonantly excited GaAs quantum wells. The microscopic theory assigns the observed spectral changes to a unique mixture of electron-hole plasma, exciton, and polarization effects. Strong transient gain is observed only under co-circular pump-probe conditions and is attributed to the transfer of pump-induced coherences to the probe.

Published
2009
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5. Discovery of IRAK4 Inhibitor 16

Author

Schafer, M., primary, Bothe, U., additional, Schmidt, N., additional, Gunther, J., additional, Nubbemeyer, R., additional, Siebeneicher, H., additional, Ring, S., additional, Boemer, U., additional, Peters, M., additional, Denner, K., additional, Himmel, H., additional, Sutter, A., additional, Terebesi, I., additional, Lange, M., additional, Wenger, A.M., additional, Guimond, N., additional, Thaler, T., additional, Platzek, J., additional, Eberspaecher, U., additional, Steuber, H., additional, Steinmeyer, A., additional, and Zollner, T.M., additional

Published
2023
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6. Discovery of IRAK4 Inhibitor 23

Author

Schafer, M., primary, Bothe, U., additional, Schmidt, N., additional, Gunther, J., additional, Nubbemeyer, R., additional, Siebeneicher, H., additional, Ring, S., additional, Boemer, U., additional, Peters, M., additional, Denner, K., additional, Himmel, H., additional, Sutter, A., additional, Terebesi, I., additional, Lange, M., additional, Wenger, A.M., additional, Guimond, N., additional, Thaler, T., additional, Platzek, J., additional, Eberspaecher, U., additional, Steuber, H., additional, Steinmeyer, A., additional, and Zollner, T.M., additional

Published
2023
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7. Discovery of IRAK4 Inhibitor 38

Author

Schafer, M., primary, Bothe, U., additional, Schmidt, N., additional, Gunther, J., additional, Nubbemeyer, R., additional, Siebeneicher, H., additional, Ring, S., additional, Boemer, U., additional, Peters, M., additional, Denner, K., additional, Himmel, H., additional, Sutter, A., additional, Terebesi, I., additional, Lange, M., additional, Wenger, A.M., additional, Guimond, N., additional, Thaler, T., additional, Platzek, J., additional, Eberspaecher, U., additional, Steuber, H., additional, Steinmeyer, A., additional, and Zollner, T.M., additional

Published
2023
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8. Factors associated with severe COVID-19 in people with idiopathic inflammatory myopathy: results from the COVID-19 Global Rheumatology Alliance physician-reported registry

Author

Yeoh, S, Gianfrancesco, M, Lawson-Tovey, S, Hyrich, K, Strangfeld, A, Gossec, L, Carmona, L, Mateus, E, Schafer, M, Richez, C, Hachulla, E, Holmqvist, M, Scire, C, Lorenz, H, Voll, R, Hasseli, R, Jayatilleke, A, Hsu, T, D'Silva, K, Pimentel-Quiroz, V, Vasquez Del Mercado, M, Shinjo, S, Neto, E, Junior, L, De Oliveira E Silva Montandon, A, Pons-Estel, G, Ornella, S, D'Angelo Exeni, M, Velozo, E, Jordan, P, Sirotich, E, Hausmann, J, Liew, J, Jacobsohn, L, Gore-Massy, M, Sufka, P, Grainger, R, Bhana, S, Wallace, Z, Robinson, P, Yazdany, J, Machado, P, Yeoh S. -A., Gianfrancesco M., Lawson-Tovey S., Hyrich K. L., Strangfeld A., Gossec L., Carmona L., Mateus E. F., Schafer M., Richez C., Hachulla E., Holmqvist M., Scire C. A., Lorenz H. -M., Voll R. E., Hasseli R., Jayatilleke A., Hsu T. Y. -T., D'Silva K. M., Pimentel-Quiroz V. R., Vasquez Del Mercado M., Shinjo S. K., Neto E. T. D. R., Junior L. F. D. R., De Oliveira E Silva Montandon A. C., Pons-Estel G. J., Ornella S., D'Angelo Exeni M. E., Velozo E., Jordan P., Sirotich E., Hausmann J. S., Liew J. W., Jacobsohn L., Gore-Massy M., Sufka P., Grainger R., Bhana S., Wallace Z., Robinson P. C., Yazdany J., MacHado P. M., Yeoh, S, Gianfrancesco, M, Lawson-Tovey, S, Hyrich, K, Strangfeld, A, Gossec, L, Carmona, L, Mateus, E, Schafer, M, Richez, C, Hachulla, E, Holmqvist, M, Scire, C, Lorenz, H, Voll, R, Hasseli, R, Jayatilleke, A, Hsu, T, D'Silva, K, Pimentel-Quiroz, V, Vasquez Del Mercado, M, Shinjo, S, Neto, E, Junior, L, De Oliveira E Silva Montandon, A, Pons-Estel, G, Ornella, S, D'Angelo Exeni, M, Velozo, E, Jordan, P, Sirotich, E, Hausmann, J, Liew, J, Jacobsohn, L, Gore-Massy, M, Sufka, P, Grainger, R, Bhana, S, Wallace, Z, Robinson, P, Yazdany, J, Machado, P, Yeoh S. -A., Gianfrancesco M., Lawson-Tovey S., Hyrich K. L., Strangfeld A., Gossec L., Carmona L., Mateus E. F., Schafer M., Richez C., Hachulla E., Holmqvist M., Scire C. A., Lorenz H. -M., Voll R. E., Hasseli R., Jayatilleke A., Hsu T. Y. -T., D'Silva K. M., Pimentel-Quiroz V. R., Vasquez Del Mercado M., Shinjo S. K., Neto E. T. D. R., Junior L. F. D. R., De Oliveira E Silva Montandon A. C., Pons-Estel G. J., Ornella S., D'Angelo Exeni M. E., Velozo E., Jordan P., Sirotich E., Hausmann J. S., Liew J. W., Jacobsohn L., Gore-Massy M., Sufka P., Grainger R., Bhana S., Wallace Z., Robinson P. C., Yazdany J., and MacHado P. M.

Abstract

Objectives To investigate factors associated with severe COVID-19 in people with idiopathic inflammatory myopathy (IIM). Methods Demographic data, clinical characteristics and COVID-19 outcome severity of adults with IIM were obtained from the COVID-19 Global Rheumatology Alliance physician-reported registry. A 3-point ordinal COVID-19 severity scale was defined: (1) no hospitalisation, (2) hospitalisation (and no death) and (3) death. ORs were estimated using multivariable ordinal logistic regression. Sensitivity analyses were performed using a 4-point ordinal scale: (1) no hospitalisation, (2) hospitalisation with no oxygen (and no death), (3) hospitalisation with oxygen/ventilation (and no death) and 4) death. Results Of 348 patients, 48% were not hospitalised, 39% were hospitalised (and did not die) and 13% died. Older age (OR=1.59/decade, 95% CI 1.31 to 1.91), high disease activity (OR=3.50, 95% CI 1.25 to 9.83; vs remission), ≥2 comorbidities (OR=2.63, 95% CI 1.39 to 4.98; vs none), prednisolone-equivalent dose >7.5 mg/day (OR=2.40, 95% CI 1.09 to 5.28; vs no intake) and exposure to rituximab (OR=2.71, 95% CI 1.28 to 5.72; vs conventional synthetic disease-modifying antirheumatic drugs only) were independently associated with severe COVID-19. In addition to these variables, in the sensitivity analyses, male sex (OR range: 1.65-1.83; vs female) was also significantly associated with severe outcomes, while COVID-19 diagnosis after 1 October 2020 (OR range: 0.51-0.59; vs on/before 15 June 2020) was significantly associated with less severe outcomes, but these associations were not significant in the main model (OR=1.57, 95% CI 0.95 to 2.59; and OR=0.61, 95% CI 0.37 to 1.00; respectively). Conclusions This is the first large registry data on outcomes of COVID-19 in people with IIM. Older age, male sex, higher comorbidity burden, high disease activity, prednisolone-equivalent dose >7.5 mg/day and rituximab exposure were associated with severe COVID-19. These

Published
2022

9. Characteristics and Outcomes of People With Gout Hospitalized Due to COVID-19: Data From the COVID-19 Global Rheumatology Alliance Physician-Reported Registry

Author

Jatuworapruk, K, Montgomery, A, Gianfrancesco, M, Conway, R, Durcan, L, Graef, E, Jayatilleke, A, Keen, H, Kilian, A, Young, K, Carmona, L, Cogo, A, Duarte-Garcia, A, Gossec, L, Hasseli, R, Hyrich, K, Langlois, V, Lawson-Tovey, S, Malcata, A, Mateus, E, Schafer, M, Scire, C, Sigurdardottir, V, Sparks, J, Strangfeld, A, Xavier, R, Bhana, S, Gore-Massy, M, Hausmann, J, Liew, J, Sirotich, E, Sufka, P, Wallace, Z, Machado, P, Yazdany, J, Grainger, R, Robinson, P, Jatuworapruk K., Montgomery A., Gianfrancesco M., Conway R., Durcan L., Graef E. R., Jayatilleke A., Keen H., Kilian A., Young K., Carmona L., Cogo A. K., Duarte-Garcia A., Gossec L., Hasseli R., Hyrich K. L., Langlois V., Lawson-Tovey S., Malcata A., Mateus E. F., Schafer M., Scire C. A., Sigurdardottir V., Sparks J. A., Strangfeld A., Xavier R. M., Bhana S., Gore-Massy M., Hausmann J., Liew J. W., Sirotich E., Sufka P., Wallace Z., Machado P. M., Yazdany J., Grainger R., Robinson P. C., Jatuworapruk, K, Montgomery, A, Gianfrancesco, M, Conway, R, Durcan, L, Graef, E, Jayatilleke, A, Keen, H, Kilian, A, Young, K, Carmona, L, Cogo, A, Duarte-Garcia, A, Gossec, L, Hasseli, R, Hyrich, K, Langlois, V, Lawson-Tovey, S, Malcata, A, Mateus, E, Schafer, M, Scire, C, Sigurdardottir, V, Sparks, J, Strangfeld, A, Xavier, R, Bhana, S, Gore-Massy, M, Hausmann, J, Liew, J, Sirotich, E, Sufka, P, Wallace, Z, Machado, P, Yazdany, J, Grainger, R, Robinson, P, Jatuworapruk K., Montgomery A., Gianfrancesco M., Conway R., Durcan L., Graef E. R., Jayatilleke A., Keen H., Kilian A., Young K., Carmona L., Cogo A. K., Duarte-Garcia A., Gossec L., Hasseli R., Hyrich K. L., Langlois V., Lawson-Tovey S., Malcata A., Mateus E. F., Schafer M., Scire C. A., Sigurdardottir V., Sparks J. A., Strangfeld A., Xavier R. M., Bhana S., Gore-Massy M., Hausmann J., Liew J. W., Sirotich E., Sufka P., Wallace Z., Machado P. M., Yazdany J., Grainger R., and Robinson P. C.

Abstract

Objective To describe people with gout who were diagnosed with coronavirus disease 2019 (COVID-19) and hospitalized and to characterize their outcomes. Methods Data on patients with gout hospitalized for COVID-19 between March 12, 2020, and October 25, 2021, were extracted from the COVID-19 Global Rheumatology Alliance registry. Descriptive statistics were used to describe the demographics, comorbidities, medication exposures, and COVID-19 outcomes including oxygenation or ventilation support and death. Results One hundred sixty-three patients with gout who developed COVID-19 and were hospitalized were included. The mean age was 63 years, and 85% were male. The majority of the group lived in the Western Pacific Region (35%) and North America (18%). Nearly half (46%) had two or more comorbidities, with hypertension (56%), cardiovascular disease (28%), diabetes mellitus (26%), chronic kidney disease (25%), and obesity (23%) being the most common. Glucocorticoids and colchicine were used pre-COVID-19 in 11% and 12% of the cohort, respectively. Over two thirds (68%) of the cohort required supplemental oxygen or ventilatory support during hospitalization. COVID-19-related death was reported in 16% of the overall cohort, with 73% of deaths documented in people with two or more comorbidities. Conclusion This cohort of people with gout and COVID-19 who were hospitalized had high frequencies of ventilatory support and death. This suggests that patients with gout who were hospitalized for COVID-19 may be at risk of poor outcomes, perhaps related to known risk factors for poor outcomes, such as age and presence of comorbidity.

Published
2022

10. COVID-19 and socio-materially bounded experimentation in food practices: insights from seven countries

Author

Hoolohan, C, Wertheim-Heck, S, Devaux, F, Domaneschi, L, Dubuisson-Quellier, S, Schafer, M, Wethal, U, Hoolohan C., Wertheim-Heck S. C. O., Devaux F., Domaneschi L., Dubuisson-Quellier S., Schafer M., Wethal U. B., Hoolohan, C, Wertheim-Heck, S, Devaux, F, Domaneschi, L, Dubuisson-Quellier, S, Schafer, M, Wethal, U, Hoolohan C., Wertheim-Heck S. C. O., Devaux F., Domaneschi L., Dubuisson-Quellier S., Schafer M., and Wethal U. B.

Abstract

COVID-19 has caused unprecedented disruption to previously settled everyday routines, prompting a period of forced experimentation as people have adjusted to rapid changes in their private and working lives. For discussions regarding consumption, this period of experimentation has been interesting, as the apparent instability has disturbed the ongoing trajectory of consumption practices, and with it has created possibilities for a transition toward sustainability. In this article, we examine food practices (e.g., food shopping, preparation, and eating) in seven countries (France, Germany, Italy, Netherlands, Norway, UK, and Vietnam) to assess what we can learn to accelerate transitions toward sustainable consumption. Grounded in a practice theoretical approach, our empirical analysis shows how disruption of everyday routines has generated socio-materially bounded experimentation. We demonstrate commonalities across contexts in how lockdown measures have restricted the performance of previously taken-for-granted practices. We also show diversity in experimentation as food consumption is entangled in other everyday practices. Our study, on one hand, portrays how the adaptation of food practices allows disruption to be managed, demonstrating creativity in working within and around restrictions to continue to provide services for everyday life. On the other hand, we reveal that the capacity of experimentation is not evenly distributed among people and this variation helps in identifying the wider socio-material conditions that constrain and enable opportunities for readjustment. Understanding disparities that affect experimentation (e.g., integration of food practices with work and caring practices) is informative when thinking about how to stimulate sustainability transformations in food practices and provides critical reflections on strategies to enable sustainable consumption.

Published
2022

11. Dexmedetomidine and Propofol Sedation in Critically Ill Patients and Dose-associated 90-Day Mortality: A Secondary Cohort Analysis of a Randomized Controlled Trial (SPICE III)

Author

Shehabi, Yahya, primary, Serpa Neto, Ary, additional, Bellomo, Rinaldo, additional, Howe, Belinda D., additional, Arabi, Yaseen M., additional, Bailey, Michael, additional, Bass, Frances E., additional, Bin Kadiman, Suhaini, additional, McArthur, Colin J., additional, Reade, Michael C., additional, Seppelt, Ian M., additional, Takala, Jukka, additional, Wise, Matt P., additional, Webb, Steve A., additional, Mashonganyika, C., additional, McKee, H., additional, Tonks, A., additional, Donnelly, A., additional, Hemmings, N., additional, O’Kane, S., additional, Blakemore, A., additional, Butler, M., additional, Cowdrey, K., additional, Dalton, J., additional, Gilder, E., additional, Long, S., additional, McCarthy, L., additional, McGuinness, S., additional, Parke, R., additional, Chen, Y., additional, McArthur, C., additional, McConnochie, R., additional, Newby, L., additional, Bellomo, R., additional, Eastwood, G., additional, Peck, L., additional, Young, H., additional, Boschert, C., additional, Edington, J., additional, Fletcher, J., additional, Smith, J., additional, Nand, K., additional, Raza, A., additional, Sara, T., additional, Bennett-Britton, J., additional, Bewley, J., additional, Bodenham, V., additional, Cole, L., additional, Driver, K., additional, Grimmer, L., additional, Howie, L., additional, Searles, C., additional, Sweet, K., additional, Webster, D., additional, van Berkel, A., additional, Connor, H., additional, Dennett, J., additional, van Der Graaff, M., additional, Henderson, S., additional, Mehrtens, J., additional, Miller, K., additional, Minto, E., additional, Morris, A., additional, Noble, S., additional, Parker, K., additional, Bulfin, L., additional, Hart, N., additional, Shepherd, K., additional, Vij, S., additional, Dickson, S., additional, Elloway, E., additional, Ferguson, C., additional, Jackson, R., additional, MacNaughton, P., additional, Marner, M., additional, Squire, R., additional, Waddy, S., additional, Wafer, P., additional, Welbourne, J., additional, Ashcroft, P., additional, Chambler, D., additional, Dukes, S., additional, Harris, A., additional, Horton, S., additional, Sharpe, S., additional, Williams, P., additional, Williams, S., additional, Bailey, M., additional, Blazquez, E., additional, France, D., additional, Hutchison, R., additional, O’Connor, A., additional, Comadira, G., additional, Gough, M., additional, Tallott, M., additional, Bastick, M., additional, Cameron, R., additional, Donovan, S., additional, Ellis, K., additional, Gaur, A., additional, Gregory, R., additional, Naumoff, J., additional, Turner, E., additional, White, M., additional, Au, K. F. J., additional, Fratzia, J., additional, Treloar, S., additional, Lim, C. H., additional, Maseeda, Y., additional, Tan, A. P., additional, Tang, C. L., additional, Yong, C. Y., additional, Akaltan, M., additional, Berger, S., additional, Blaser, D., additional, Fazlija, L., additional, Jong, M. L., additional, Lensch, M., additional, Ludwig, R., additional, Merz, T., additional, Nettelbeck, K., additional, Roth, M., additional, Schafer, M., additional, Takala, J., additional, Wehr, A., additional, Zacharias, D., additional, Amran, R., additional, Ashraf, H. N., additional, Azmi, N., additional, Basri, N., additional, Burhanuddin, H., additional, Hadinata, Y., additional, Hamdan, A., additional, Kadiman, S., additional, Rashid, A. I. Y. M., additional, Sabran, I. N., additional, Sulaiman, S., additional, Zabidi, I. N., additional, Al-Dawood, A., additional, Aljuaid, M., additional, Anizi, H. Al, additional, Saeedi, A. Al, additional, Arabi, Y., additional, Dbsawy, M., additional, Deeb, A., additional, Hegazy, M., additional, Magdi, I., additional, Clarey, E., additional, Corcoran, E., additional, Finney, C., additional, Harris, C., additional, Hopkins, P., additional, Noble, H., additional, Thompson, L., additional, Williams, T., additional, Dumlao, L. A., additional, Bassam, R., additional, Hassan, M. A., additional, Naseem, N., additional, Al-Kurdi, M. H., additional, Al-Harthy, A. M., additional, Bernard, S., additional, Sebafundi, L., additional, Serban, C., additional, Lim, S. K., additional, Mazidah, N., additional, Saidin, N., additional, Sjamsuddin, N., additional, Tan, I. T. A., additional, Zabidi, N., additional, Brain, M., additional, Mineall, S., additional, Kanhere, M., additional, Soar, N., additional, Kadir, N. Abd, additional, Abdullah, N. H., additional, Awang, R., additional, Emperan, Z., additional, Husin, N. S., additional, Ismail, N. I., additional, Ismail, S. Z., additional, Khadzali, F. N. A. Mohd, additional, Norddin, M. F., additional, Aguila, J., additional, Bold, C., additional, Clatworthy, B., additional, Dias, A., additional, Hogan, C., additional, Kazemi, A., additional, Lai, V., additional, Song, R., additional, Williams, A., additional, Bhatia, D., additional, Elliot, S., additional, Galt, P., additional, Lavrans, K., additional, Ritchie, P., additional, Wang, A., additional, Gresham, R., additional, Lowrey, J., additional, Masters, K., additional, Palejs, P., additional, Seppelt, I., additional, Symonds, F., additional, Weisbrodt, L., additional, Whitehead, C., additional, Babio-Galan, M., additional, Calder, V., additional, Clement, I., additional, Harrison, A., additional, McCullagh, I., additional, Scott, C., additional, Bevan, R., additional, Caniba, S., additional, Hacking, D., additional, Maher, L., additional, Azzolini, M. L., additional, Beccaria, P., additional, Colombo, S., additional, Landoni, G., additional, Leggieri, C., additional, Luca, C., additional, Mamo, D., additional, Moizo, E., additional, Monti, G., additional, Mucci, M., additional, Zangrillo, A., additional, Albania, M., additional, Arora, S., additional, Shi, Y., additional, Abudayah, A., additional, Almekhlafi, G., additional, Al Amodi, E., additional, Al Samarrai, S., additional, Badawi, M., additional, Caba, R. Cubio, additional, Elffaki, O., additional, Mandourah, Y., additional, Valerio, J., additional, Joyce, C., additional, Meyer, J., additional, Saylor, E., additional, Venkatesh, B., additional, Venz, E., additional, Walsham, J., additional, Wetzig, K., additional, Khoo, T. M., additional, Liew, J. E. S., additional, Sakthi, A. N., additional, Zulkurnain, A., additional, Bamford, A., additional, Bergin, C., additional, Carrera, R., additional, Cooper, L., additional, Despy, L., additional, Harkett, S., additional, Mee, L., additional, Reeves, E., additional, Snelson, C., additional, Spruce, E., additional, Cooper, G., additional, Hodgson, R., additional, Pearson, D., additional, Rosbergen, M., additional, Ali, M. N., additional, Bahar, N. I., additional, Ismail, A., additional, Ismail, W. N. W., additional, Samat, N. M., additional, Piah, N. S. M., additional, Rahman, R. Abd, additional, Duroux, M., additional, Ratcliffe, M., additional, Warhurst, T., additional, Buehner, U., additional, Williams, E., additional, Jacques, N., additional, Keating, L., additional, Macgill, S., additional, Tamang, K. L., additional, Tolan, N., additional, Walden, A., additional, Bower, R., additional, Cranshaw, J., additional, Molloy, K., additional, Pitts, S., additional, Butler, J., additional, Dunlop, R., additional, Fourie, C., additional, Jarrett, P., additional, Lassig-Smith, M., additional, Livermore, A., additional, O’Donoghue, S., additional, Reade, M., additional, Starr, T., additional, Stuart, J., additional, Campbell, L., additional, Phillips, M., additional, Stephens, D., additional, Thomas, J., additional, Cooper, D., additional, McAllister, R., additional, Andrew, G., additional, Barclay, L., additional, Dawson, H., additional, Griffith, D. M., additional, Hope, D., additional, Wojcik, G., additional, McCulloch, C., additional, Paterson, R., additional, Ascough, L., additional, Paisley, C., additional, Patrick-Heselton, J., additional, Shaw, D., additional, Waugh, V., additional, Williams, K., additional, Welters, I., additional, Barge, D., additional, Jordan, A., additional, MacIsaac, C., additional, Rechnitzer, T., additional, Bass, F., additional, Gatward, J., additional, Hammond, N., additional, Janin, P., additional, Stedman, W., additional, Yarad, E., additional, Razak, N. A., additional, Dzulkipli, N., additional, Jong, S. L., additional, Asen, K., additional, Voon, W. L., additional, Liew, S., additional, Ball, J., additional, Barnes, V., additional, Dalton, C., additional, Farnell-Ward, S., additional, Farrah, H., additional, Maher, K., additional, Mellinghoff, J., additional, Ryan, C., additional, Shirley, P., additional, Conlon, L., additional, Glover, A., additional, Martin-Loeches, I., additional, O’Toole, E., additional, Ewan, J., additional, Ferrier, J., additional, Litton, E., additional, Webb, S. A., additional, Berry, W., additional, Blanco Alonso, U., additional, Bociek, A., additional, Campos, S., additional, Jawara, S., additional, Hanks, F., additional, Kelly, A., additional, Lei, K., additional, McKenzie, C., additional, Ostermann, M., additional, Wan, R., additional, Al-Soufi, S., additional, Leow, S., additional, McCann, K., additional, Reynolds, C., additional, Brickell, K., additional, Fahey, C., additional, Hays, L., additional, Hyde, N., additional, Nichol, A., additional, Ryan, D., additional, Brailsford, J., additional, Buckley, A., additional, Forbes, L., additional, Maguire, T., additional, Moore, J., additional, Murray, L., additional, Ghosh, A., additional, Park, M., additional, Said, S., additional, Visser, A., additional, Abidin, H. Z., additional, Ali, S., additional, Hassan, M. H., additional, Omar, S. C., additional, Shukeri, W. F. W., additional, Brealey, D., additional, Bercades, G., additional, Blackburn, E., additional, Macallum, N., additional, Macklin, A., additional, Ryu, J. H., additional, Tam, K., additional, Smyth, D., additional, Arif, A., additional, Bassford, C., additional, Morgan, C., additional, Swann, C., additional, Ward, G., additional, Wild, L., additional, Bone, A., additional, Elderkin, T., additional, Green, D., additional, Sach, D., additional, Salerno, T., additional, Simpson, N., additional, Brohi, F., additional, Clark, M., additional, Williams, L., additional, Brooks, J., additional, Cocks, E., additional, Cole, J., additional, Curtin, J., additional, Davies, R., additional, Hill, H., additional, Morgan, M., additional, Palmer, N., additional, Whitton, C., additional, Wise, M., additional, Baskaran, P., additional, Hasan, M. S., additional, Tham, L. Y., additional, Sol Cruz, R., additional, Dinsdale, D., additional, Edney, S., additional, Firkin, C., additional, FitzJohn, F., additional, Hill, G., additional, Hunt, A., additional, Hurford, S., additional, Jones, G., additional, Judd, H., additional, Latimer-Bell, C., additional, Lawrence, C., additional, Lesona, E., additional, Navarra, L., additional, Robertson, Y., additional, Smellie, H., additional, Vucago, A. M., additional, Young, P., additional, Clark, P., additional, Kong, J., additional, Ho, J., additional, Nayyar, V., additional, and Skelly, C., additional

Published
2023
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12. Have Middle-Aged and Older Americans Become Lonelier? 20-Year Trends From the Health and Retirement Study.

Author

Schafer, M, Surkalim, DL, Clare, PJ, Eres, R, Gebel, K, Bauman, A, Ding, D, Schafer, M, Surkalim, DL, Clare, PJ, Eres, R, Gebel, K, Bauman, A, and Ding, D

Abstract

OBJECTIVES: Despite media and public dialog portraying loneliness as a worsening problem, little is known about how the prevalence of loneliness has changed over time. Our study aims to identify (a) temporal trends in episodic and sustained loneliness (lonely in 1 wave vs consistently lonely in 3 consecutive waves); (b) trends across sociodemographic subgroups by sex, race/ethnicity, birth cohort, education, employment status, marital status, and living alone; and (c) longitudinal predictors of loneliness in middle-aged and older Americans (≥50 years). METHODS: Based on Waves 3 (1996) to 14 (2018) of the Health and Retirement Study (n = 18,841-23,227), we conducted a series of lagged mixed-effects Poisson regression models to assess trends of episodic and sustained loneliness in the overall and sociodemographic subgroup samples (by sex, race/ethnicity, birth cohort, education, employment, relationship, and living alone status). To examine the predictors of episodic and sustained loneliness, we used a multivariate mixed-effects Poisson regression model with all sociodemographic variables entered into the same model. RESULTS: Episodic loneliness prevalence decreased from 20.1% to 15.5% and sustained loneliness from 4.6% to 3.6%. Trends were similar across most subgroups. Males, Caucasians, those born in 1928-1945, with university education, working, married/partnered, and those not living alone reported lower episodic and sustained loneliness, although associations with sustained loneliness were stronger. DISCUSSION: Contrary to common perceptions, loneliness has decreased over 20 years of follow-up in middle-aged and older Americans. Several sociodemographic subgroups have been identified as having a higher risk of loneliness, prompting targeted public health attention.

Published
2023

13. Factors associated with COVID-19-related death in people with rheumatic diseases: Results from the COVID-19 Global Rheumatology Alliance physician-reported registry

Author

Strangfeld, A, Schafer, M, Gianfrancesco, M, Lawson-Tovey, S, Liew, J, Ljung, L, Mateus, E, Richez, C, Santos, M, Schmajuk, G, Scire, C, Sirotich, E, Sparks, J, Sufka, P, Thomas, T, Trupin, L, Wallace, Z, Al-Adely, S, Bachiller-Corral, J, Bhana, S, Cacoub, P, Carmona, L, Costello, R, Costello, W, Gossec, L, Grainger, R, Hachulla, E, Hasseli, R, Hausmann, J, Hyrich, K, Izadi, Z, Jacobsohn, L, Katz, P, Kearsley-Fleet, L, Robinson, P, Yazdany, J, Machado, P, Strangfeld A., Schafer M., Gianfrancesco M. A., Lawson-Tovey S., Liew J. W., Ljung L., Mateus E. F., Richez C., Santos M. J., Schmajuk G., Scire C. A., Sirotich E., Sparks J. A., Sufka P., Thomas T., Trupin L., Wallace Z. S., Al-Adely S., Bachiller-Corral J., Bhana S., Cacoub P., Carmona L., Costello R., Costello W., Gossec L., Grainger R., Hachulla E., Hasseli R., Hausmann J. S., Hyrich K. L., Izadi Z., Jacobsohn L., Katz P., Kearsley-Fleet L., Robinson P. C., Yazdany J., Machado P. M., Strangfeld, A, Schafer, M, Gianfrancesco, M, Lawson-Tovey, S, Liew, J, Ljung, L, Mateus, E, Richez, C, Santos, M, Schmajuk, G, Scire, C, Sirotich, E, Sparks, J, Sufka, P, Thomas, T, Trupin, L, Wallace, Z, Al-Adely, S, Bachiller-Corral, J, Bhana, S, Cacoub, P, Carmona, L, Costello, R, Costello, W, Gossec, L, Grainger, R, Hachulla, E, Hasseli, R, Hausmann, J, Hyrich, K, Izadi, Z, Jacobsohn, L, Katz, P, Kearsley-Fleet, L, Robinson, P, Yazdany, J, Machado, P, Strangfeld A., Schafer M., Gianfrancesco M. A., Lawson-Tovey S., Liew J. W., Ljung L., Mateus E. F., Richez C., Santos M. J., Schmajuk G., Scire C. A., Sirotich E., Sparks J. A., Sufka P., Thomas T., Trupin L., Wallace Z. S., Al-Adely S., Bachiller-Corral J., Bhana S., Cacoub P., Carmona L., Costello R., Costello W., Gossec L., Grainger R., Hachulla E., Hasseli R., Hausmann J. S., Hyrich K. L., Izadi Z., Jacobsohn L., Katz P., Kearsley-Fleet L., Robinson P. C., Yazdany J., and Machado P. M.

Abstract

Objectives To determine factors associated with COVID-19-related death in people with rheumatic diseases. Methods Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. Results Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. Conclusion Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dos

Published
2021

14. Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry

Author

Sparks, J, Wallace, Z, Seet, A, Gianfrancesco, M, Izadi, Z, Hyrich, K, Strangfeld, A, Gossec, L, Carmona, L, Mateus, E, Lawson-Tovey, S, Trupin, L, Rush, S, Katz, P, Schmajuk, G, Jacobsohn, L, Wise, L, Gilbert, E, Duarte-Garcia, A, Valenzuela-Almada, M, Pons-Estel, G, Isnardi, C, Berbotto, G, Hsu, T, D'Silva, K, Patel, N, Kearsley-Fleet, L, Schafer, M, Ribeiro, S, Al Emadi, S, Tidblad, L, Scire, C, Raffeiner, B, Thomas, T, Flipo, R, Avouac, J, Seror, R, Bernardes, M, Cunha, M, Hasseli, R, Schulze-Koops, H, Muller-Ladner, U, Specker, C, De Souza, V, Da Mota, L, Gomides, A, Dieude, P, Nikiphorou, E, Kronzer, V, Singh, N, Ugarte-Gil, M, Wallace, B, Akpabio, A, Thomas, R, Bhana, S, Costello, W, Grainger, R, Hausmann, J, Liew, J, Sirotich, E, Sufka, P, Robinson, P, Machado, P, Yazdany, J, Sparks J. A., Wallace Z. S., Seet A. M., Gianfrancesco M. A., Izadi Z., Hyrich K. L., Strangfeld A., Gossec L., Carmona L., Mateus E. F., Lawson-Tovey S., Trupin L., Rush S., Katz P., Schmajuk G., Jacobsohn L., Wise L., Gilbert E. L., Duarte-Garcia A., Valenzuela-Almada M. O., Pons-Estel G. J., Isnardi C. A., Berbotto G. A., Hsu T. Y. -T., D'Silva K. M., Patel N. J., Kearsley-Fleet L., Schafer M., Ribeiro S. L. E., Al Emadi S., Tidblad L., Scire C. A., Raffeiner B., Thomas T., Flipo R. -M., Avouac J., Seror R., Bernardes M., Cunha M. M., Hasseli R., Schulze-Koops H., Muller-Ladner U., Specker C., De Souza V. A., Da Mota L. M. H., Gomides A. P. M., Dieude P., Nikiphorou E., Kronzer V. L., Singh N., Ugarte-Gil M. F., Wallace B., Akpabio A., Thomas R., Bhana S., Costello W., Grainger R., Hausmann J. S., Liew J. W., Sirotich E., Sufka P., Robinson P. C., MacHado P. M., Yazdany J., Sparks, J, Wallace, Z, Seet, A, Gianfrancesco, M, Izadi, Z, Hyrich, K, Strangfeld, A, Gossec, L, Carmona, L, Mateus, E, Lawson-Tovey, S, Trupin, L, Rush, S, Katz, P, Schmajuk, G, Jacobsohn, L, Wise, L, Gilbert, E, Duarte-Garcia, A, Valenzuela-Almada, M, Pons-Estel, G, Isnardi, C, Berbotto, G, Hsu, T, D'Silva, K, Patel, N, Kearsley-Fleet, L, Schafer, M, Ribeiro, S, Al Emadi, S, Tidblad, L, Scire, C, Raffeiner, B, Thomas, T, Flipo, R, Avouac, J, Seror, R, Bernardes, M, Cunha, M, Hasseli, R, Schulze-Koops, H, Muller-Ladner, U, Specker, C, De Souza, V, Da Mota, L, Gomides, A, Dieude, P, Nikiphorou, E, Kronzer, V, Singh, N, Ugarte-Gil, M, Wallace, B, Akpabio, A, Thomas, R, Bhana, S, Costello, W, Grainger, R, Hausmann, J, Liew, J, Sirotich, E, Sufka, P, Robinson, P, Machado, P, Yazdany, J, Sparks J. A., Wallace Z. S., Seet A. M., Gianfrancesco M. A., Izadi Z., Hyrich K. L., Strangfeld A., Gossec L., Carmona L., Mateus E. F., Lawson-Tovey S., Trupin L., Rush S., Katz P., Schmajuk G., Jacobsohn L., Wise L., Gilbert E. L., Duarte-Garcia A., Valenzuela-Almada M. O., Pons-Estel G. J., Isnardi C. A., Berbotto G. A., Hsu T. Y. -T., D'Silva K. M., Patel N. J., Kearsley-Fleet L., Schafer M., Ribeiro S. L. E., Al Emadi S., Tidblad L., Scire C. A., Raffeiner B., Thomas T., Flipo R. -M., Avouac J., Seror R., Bernardes M., Cunha M. M., Hasseli R., Schulze-Koops H., Muller-Ladner U., Specker C., De Souza V. A., Da Mota L. M. H., Gomides A. P. M., Dieude P., Nikiphorou E., Kronzer V. L., Singh N., Ugarte-Gil M. F., Wallace B., Akpabio A., Thomas R., Bhana S., Costello W., Grainger R., Hausmann J. S., Liew J. W., Sirotich E., Sufka P., Robinson P. C., MacHado P. M., and Yazdany J.

Abstract

Objective To investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA). Methods We analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders. Results Of 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity. Conclusions People with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.

Published
2021

15. EUREC4A

Author

Stevens, B, Bony, S, Farrell, D, Ament, F, Blyth, A, Fairall, C, Karstensen, J, Quinn, P, Speich, S, Acquistapace, C, Aemisegger, F, Albright, A, Bellenger, H, Bodenschatz, E, Caesar, K, Chewitt-Lucas, R, De Boer, G, Delanoe, J, Denby, L, Ewald, F, Fildier, B, Forde, M, George, G, Gross, S, Hagen, M, Hausold, A, Heywood, K, Hirsch, L, Jacob, M, Jansen, F, Kinne, S, Klocke, D, Kolling, T, Konow, H, Lothon, M, Mohr, W, Naumann, A, Nuijens, L, Olivier, L, Pincus, R, Pohlker, M, Reverdin, G, Roberts, G, Schnitt, S, Schulz, H, Pier Siebesma, A, Stephan, C, Sullivan, P, Touze-Peiffer, L, Vial, J, Vogel, R, Zuidema, P, Alexander, N, Alves, L, Arixi, S, Asmath, H, Bagheri, G, Baier, K, Bailey, A, Baranowski, D, Baron, A, Barrau, S, Barrett, P, Batier, F, Behrendt, A, Bendinger, A, Beucher, F, Bigorre, S, Blades, E, Blossey, P, Bock, O, Boing, S, Bosser, P, Bourras, D, Bouruet-Aubertot, P, Bower, K, Branellec, P, Branger, H, Brennek, M, Brewer, A, Brilouet, P, Brugmann, B, Buehler, S, Burke, E, Burton, R, Calmer, R, Canonici, J, Carton, X, Cato, G, Charles, J, Chazette, P, Chen, Y, Chilinski, M, Choularton, T, Chuang, P, Clarke, S, Coe, H, Cornet, C, Coutris, P, Couvreux, F, Crewell, S, Cronin, T, Cui, Z, Cuypers, Y, Daley, A, Damerell, G, Dauhut, T, Deneke, H, Desbios, J, Dorner, S, Donner, S, Douet, V, Drushka, K, Dutsch, M, Ehrlich, A, Emanuel, K, Emmanouilidis, A, Etienne, J, Etienne-Leblanc, S, Faure, G, Feingold, G, Ferrero, L, Fix, A, Flamant, C, Flatau, P, Foltz, G, Forster, L, Furtuna, I, Gadian, A, Galewsky, J, Gallagher, M, Gallimore, P, Gaston, C, Gentemann, C, Geyskens, N, Giez, A, Gollop, J, Gouirand, I, Gourbeyre, C, De Graaf, D, De Groot, G, Grosz, R, Guttler, J, Gutleben, M, Hall, K, Harris, G, Helfer, K, Henze, D, Herbert, C, Holanda, B, Ibanez-Landeta, A, Intrieri, J, Iyer, S, Julien, F, Kalesse, H, Kazil, J, Kellman, A, Kidane, A, Kirchner, U, Klingebiel, M, Korner, M, Kremper, L, Kretzschmar, J, Kruger, O, Kumala, W, Kurz, A, L'Hegaret, P, Labaste, M, Lachlan-Cope, T, Laing, A, Landschutzer, P, Lang, T, Lange, D, Lange, I, Laplace, C, Lavik, G, Laxenaire, R, Lebihan, C, Leandro, M, Lefevre, N, Lena, M, Lenschow, D, Li, Q, Lloyd, G, Los, S, Losi, N, Lovell, O, Luneau, C, Makuch, P, Malinowski, S, Manta, G, Marinou, E, Marsden, N, Masson, S, Maury, N, Mayer, B, Mayers-Als, M, Mazel, C, Mcgeary, W, Mcwilliams, J, Mech, M, Mehlmann, M, Meroni, A, Mieslinger, T, Minikin, A, Minnett, P, Moller, G, Avalos, Y, Muller, C, Musat, I, Napoli, A, Neuberger, A, Noisel, C, Noone, D, Nordsiek, F, Nowak, J, Oswald, L, Parker, D, Peck, C, Person, R, Philippi, M, Plueddemann, A, Pohlker, C, Portge, V, Poschl, U, Pologne, L, Posyniak, M, Prange, M, Melendez, E, Radtke, J, Ramage, K, Reimann, J, Renault, L, Reus, K, Reyes, A, Ribbe, J, Ringel, M, Ritschel, M, Rocha, C, Rochetin, N, Rottenbacher, J, Rollo, C, Royer, H, Sadoulet, P, Saffin, L, Sandiford, S, Sandu, I, Schafer, M, Schemann, V, Schirmacher, I, Schlenczek, O, Schmidt, J, Schroder, M, Schwarzenboeck, A, Sealy, A, Senff, C, Serikov, I, Shohan, S, Siddle, E, Smirnov, A, Spath, F, Spooner, B, Katharina Stolla, M, Szkolka, W, De Szoeke, S, Tarot, S, Tetoni, E, Thompson, E, Thomson, J, Tomassini, L, Totems, J, Ubele, A, Villiger, L, Von Arx, J, Wagner, T, Walther, A, Webber, B, Wendisch, M, Whitehall, S, Wiltshire, A, Wing, A, Wirth, M, Wiskandt, J, Wolf, K, Worbes, L, Wright, E, Wulfmeyer, V, Young, S, Zhang, C, Zhang, D, Ziemen, F, Zinner, T, Zoger, M, Stevens B., Bony S., Farrell D., Ament F., Blyth A., Fairall C., Karstensen J., Quinn P. K., Speich S., Acquistapace C., Aemisegger F., Albright A. L., Bellenger H., Bodenschatz E., Caesar K. -A., Chewitt-Lucas R., De Boer G., Delanoe J., Denby L., Ewald F., Fildier B., Forde M., George G., Gross S., Hagen M., Hausold A., Heywood K. J., Hirsch L., Jacob M., Jansen F., Kinne S., Klocke D., Kolling T., Konow H., Lothon M., Mohr W., Naumann A. K., Nuijens L., Olivier L., Pincus R., Pohlker M., Reverdin G., Roberts G., Schnitt S., Schulz H., Pier Siebesma A., Stephan C. C., Sullivan P., Touze-Peiffer L., Vial J., Vogel R., Zuidema P., Alexander N., Alves L., Arixi S., Asmath H., Bagheri G., Baier K., Bailey A., Baranowski D., Baron A., Barrau S., Barrett P. A., Batier F., Behrendt A., Bendinger A., Beucher F., Bigorre S., Blades E., Blossey P., Bock O., Boing S., Bosser P., Bourras D., Bouruet-Aubertot P., Bower K., Branellec P., Branger H., Brennek M., Brewer A., Brilouet P. -E., Brugmann B., Buehler S. A., Burke E., Burton R., Calmer R., Canonici J. -C., Carton X., Cato G., Charles J. A., Chazette P., Chen Y., Chilinski M. T., Choularton T., Chuang P., Clarke S., Coe H., Cornet C., Coutris P., Couvreux F., Crewell S., Cronin T., Cui Z., Cuypers Y., Daley A., Damerell G. M., Dauhut T., Deneke H., Desbios J. -P., Dorner S., Donner S., Douet V., Drushka K., Dutsch M., Ehrlich A., Emanuel K., Emmanouilidis A., Etienne J. -C., Etienne-Leblanc S., Faure G., Feingold G., Ferrero L., Fix A., Flamant C., Flatau P. J., Foltz G. R., Forster L., Furtuna I., Gadian A., Galewsky J., Gallagher M., Gallimore P., Gaston C., Gentemann C., Geyskens N., Giez A., Gollop J., Gouirand I., Gourbeyre C., De Graaf D., De Groot G. E., Grosz R., Guttler J., Gutleben M., Hall K., Harris G., Helfer K. C., Henze D., Herbert C., Holanda B., Ibanez-Landeta A., Intrieri J., Iyer S., Julien F., Kalesse H., Kazil J., Kellman A., Kidane A. T., Kirchner U., Klingebiel M., Korner M., Kremper L. A., Kretzschmar J., Kruger O., Kumala W., Kurz A., L'Hegaret P., Labaste M., Lachlan-Cope T., Laing A., Landschutzer P., Lang T., Lange D., Lange I., Laplace C., Lavik G., Laxenaire R., LeBihan C., Leandro M., Lefevre N., Lena M., Lenschow D., Li Q., Lloyd G., Los S., Losi N., Lovell O., Luneau C., Makuch P., Malinowski S., Manta G., Marinou E., Marsden N., Masson S., Maury N., Mayer B., Mayers-Als M., Mazel C., McGeary W., McWilliams J. C., Mech M., Mehlmann M., Meroni A. N., Mieslinger T., Minikin A., Minnett P., Moller G., Avalos Y. M., Muller C., Musat I., Napoli A., Neuberger A., Noisel C., Noone D., Nordsiek F., Nowak J. L., Oswald L., Parker D. J., Peck C., Person R., Philippi M., Plueddemann A., Pohlker C., Portge V., Poschl U., Pologne L., Posyniak M., Prange M., Melendez E. Q., Radtke J., Ramage K., Reimann J., Renault L., Reus K., Reyes A., Ribbe J., Ringel M., Ritschel M., Rocha C. B., Rochetin N., Rottenbacher J., Rollo C., Royer H., Sadoulet P., Saffin L., Sandiford S., Sandu I., Schafer M., Schemann V., Schirmacher I., Schlenczek O., Schmidt J., Schroder M., Schwarzenboeck A., Sealy A., Senff C. J., Serikov I., Shohan S., Siddle E., Smirnov A., Spath F., Spooner B., Katharina Stolla M., Szkolka W., De Szoeke S. P., Tarot S., Tetoni E., Thompson E., Thomson J., Tomassini L., Totems J., Ubele A. A., Villiger L., Von Arx J., Wagner T., Walther A., Webber B., Wendisch M., Whitehall S., Wiltshire A., Wing A. A., Wirth M., Wiskandt J., Wolf K., Worbes L., Wright E., Wulfmeyer V., Young S., Zhang C., Zhang D., Ziemen F., Zinner T., Zoger M., Stevens, B, Bony, S, Farrell, D, Ament, F, Blyth, A, Fairall, C, Karstensen, J, Quinn, P, Speich, S, Acquistapace, C, Aemisegger, F, Albright, A, Bellenger, H, Bodenschatz, E, Caesar, K, Chewitt-Lucas, R, De Boer, G, Delanoe, J, Denby, L, Ewald, F, Fildier, B, Forde, M, George, G, Gross, S, Hagen, M, Hausold, A, Heywood, K, Hirsch, L, Jacob, M, Jansen, F, Kinne, S, Klocke, D, Kolling, T, Konow, H, Lothon, M, Mohr, W, Naumann, A, Nuijens, L, Olivier, L, Pincus, R, Pohlker, M, Reverdin, G, Roberts, G, Schnitt, S, Schulz, H, Pier Siebesma, A, Stephan, C, Sullivan, P, Touze-Peiffer, L, Vial, J, Vogel, R, Zuidema, P, Alexander, N, Alves, L, Arixi, S, Asmath, H, Bagheri, G, Baier, K, Bailey, A, Baranowski, D, Baron, A, Barrau, S, Barrett, P, Batier, F, Behrendt, A, Bendinger, A, Beucher, F, Bigorre, S, Blades, E, Blossey, P, Bock, O, Boing, S, Bosser, P, Bourras, D, Bouruet-Aubertot, P, Bower, K, Branellec, P, Branger, H, Brennek, M, Brewer, A, Brilouet, P, Brugmann, B, Buehler, S, Burke, E, Burton, R, Calmer, R, Canonici, J, Carton, X, Cato, G, Charles, J, Chazette, P, Chen, Y, Chilinski, M, Choularton, T, Chuang, P, Clarke, S, Coe, H, Cornet, C, Coutris, P, Couvreux, F, Crewell, S, Cronin, T, Cui, Z, Cuypers, Y, Daley, A, Damerell, G, Dauhut, T, Deneke, H, Desbios, J, Dorner, S, Donner, S, Douet, V, Drushka, K, Dutsch, M, Ehrlich, A, Emanuel, K, Emmanouilidis, A, Etienne, J, Etienne-Leblanc, S, Faure, G, Feingold, G, Ferrero, L, Fix, A, Flamant, C, Flatau, P, Foltz, G, Forster, L, Furtuna, I, Gadian, A, Galewsky, J, Gallagher, M, Gallimore, P, Gaston, C, Gentemann, C, Geyskens, N, Giez, A, Gollop, J, Gouirand, I, Gourbeyre, C, De Graaf, D, De Groot, G, Grosz, R, Guttler, J, Gutleben, M, Hall, K, Harris, G, Helfer, K, Henze, D, Herbert, C, Holanda, B, Ibanez-Landeta, A, Intrieri, J, Iyer, S, Julien, F, Kalesse, H, Kazil, J, Kellman, A, Kidane, A, Kirchner, U, Klingebiel, M, Korner, M, Kremper, L, Kretzschmar, J, Kruger, O, Kumala, W, Kurz, A, L'Hegaret, P, Labaste, M, Lachlan-Cope, T, Laing, A, Landschutzer, P, Lang, T, Lange, D, Lange, I, Laplace, C, Lavik, G, Laxenaire, R, Lebihan, C, Leandro, M, Lefevre, N, Lena, M, Lenschow, D, Li, Q, Lloyd, G, Los, S, Losi, N, Lovell, O, Luneau, C, Makuch, P, Malinowski, S, Manta, G, Marinou, E, Marsden, N, Masson, S, Maury, N, Mayer, B, Mayers-Als, M, Mazel, C, Mcgeary, W, Mcwilliams, J, Mech, M, Mehlmann, M, Meroni, A, Mieslinger, T, Minikin, A, Minnett, P, Moller, G, Avalos, Y, Muller, C, Musat, I, Napoli, A, Neuberger, A, Noisel, C, Noone, D, Nordsiek, F, Nowak, J, Oswald, L, Parker, D, Peck, C, Person, R, Philippi, M, Plueddemann, A, Pohlker, C, Portge, V, Poschl, U, Pologne, L, Posyniak, M, Prange, M, Melendez, E, Radtke, J, Ramage, K, Reimann, J, Renault, L, Reus, K, Reyes, A, Ribbe, J, Ringel, M, Ritschel, M, Rocha, C, Rochetin, N, Rottenbacher, J, Rollo, C, Royer, H, Sadoulet, P, Saffin, L, Sandiford, S, Sandu, I, Schafer, M, Schemann, V, Schirmacher, I, Schlenczek, O, Schmidt, J, Schroder, M, Schwarzenboeck, A, Sealy, A, Senff, C, Serikov, I, Shohan, S, Siddle, E, Smirnov, A, Spath, F, Spooner, B, Katharina Stolla, M, Szkolka, W, De Szoeke, S, Tarot, S, Tetoni, E, Thompson, E, Thomson, J, Tomassini, L, Totems, J, Ubele, A, Villiger, L, Von Arx, J, Wagner, T, Walther, A, Webber, B, Wendisch, M, Whitehall, S, Wiltshire, A, Wing, A, Wirth, M, Wiskandt, J, Wolf, K, Worbes, L, Wright, E, Wulfmeyer, V, Young, S, Zhang, C, Zhang, D, Ziemen, F, Zinner, T, Zoger, M, Stevens B., Bony S., Farrell D., Ament F., Blyth A., Fairall C., Karstensen J., Quinn P. K., Speich S., Acquistapace C., Aemisegger F., Albright A. L., Bellenger H., Bodenschatz E., Caesar K. -A., Chewitt-Lucas R., De Boer G., Delanoe J., Denby L., Ewald F., Fildier B., Forde M., George G., Gross S., Hagen M., Hausold A., Heywood K. J., Hirsch L., Jacob M., Jansen F., Kinne S., Klocke D., Kolling T., Konow H., Lothon M., Mohr W., Naumann A. K., Nuijens L., Olivier L., Pincus R., Pohlker M., Reverdin G., Roberts G., Schnitt S., Schulz H., Pier Siebesma A., Stephan C. C., Sullivan P., Touze-Peiffer L., Vial J., Vogel R., Zuidema P., Alexander N., Alves L., Arixi S., Asmath H., Bagheri G., Baier K., Bailey A., Baranowski D., Baron A., Barrau S., Barrett P. A., Batier F., Behrendt A., Bendinger A., Beucher F., Bigorre S., Blades E., Blossey P., Bock O., Boing S., Bosser P., Bourras D., Bouruet-Aubertot P., Bower K., Branellec P., Branger H., Brennek M., Brewer A., Brilouet P. -E., Brugmann B., Buehler S. A., Burke E., Burton R., Calmer R., Canonici J. -C., Carton X., Cato G., Charles J. A., Chazette P., Chen Y., Chilinski M. T., Choularton T., Chuang P., Clarke S., Coe H., Cornet C., Coutris P., Couvreux F., Crewell S., Cronin T., Cui Z., Cuypers Y., Daley A., Damerell G. M., Dauhut T., Deneke H., Desbios J. -P., Dorner S., Donner S., Douet V., Drushka K., Dutsch M., Ehrlich A., Emanuel K., Emmanouilidis A., Etienne J. -C., Etienne-Leblanc S., Faure G., Feingold G., Ferrero L., Fix A., Flamant C., Flatau P. J., Foltz G. R., Forster L., Furtuna I., Gadian A., Galewsky J., Gallagher M., Gallimore P., Gaston C., Gentemann C., Geyskens N., Giez A., Gollop J., Gouirand I., Gourbeyre C., De Graaf D., De Groot G. E., Grosz R., Guttler J., Gutleben M., Hall K., Harris G., Helfer K. C., Henze D., Herbert C., Holanda B., Ibanez-Landeta A., Intrieri J., Iyer S., Julien F., Kalesse H., Kazil J., Kellman A., Kidane A. T., Kirchner U., Klingebiel M., Korner M., Kremper L. A., Kretzschmar J., Kruger O., Kumala W., Kurz A., L'Hegaret P., Labaste M., Lachlan-Cope T., Laing A., Landschutzer P., Lang T., Lange D., Lange I., Laplace C., Lavik G., Laxenaire R., LeBihan C., Leandro M., Lefevre N., Lena M., Lenschow D., Li Q., Lloyd G., Los S., Losi N., Lovell O., Luneau C., Makuch P., Malinowski S., Manta G., Marinou E., Marsden N., Masson S., Maury N., Mayer B., Mayers-Als M., Mazel C., McGeary W., McWilliams J. C., Mech M., Mehlmann M., Meroni A. N., Mieslinger T., Minikin A., Minnett P., Moller G., Avalos Y. M., Muller C., Musat I., Napoli A., Neuberger A., Noisel C., Noone D., Nordsiek F., Nowak J. L., Oswald L., Parker D. J., Peck C., Person R., Philippi M., Plueddemann A., Pohlker C., Portge V., Poschl U., Pologne L., Posyniak M., Prange M., Melendez E. Q., Radtke J., Ramage K., Reimann J., Renault L., Reus K., Reyes A., Ribbe J., Ringel M., Ritschel M., Rocha C. B., Rochetin N., Rottenbacher J., Rollo C., Royer H., Sadoulet P., Saffin L., Sandiford S., Sandu I., Schafer M., Schemann V., Schirmacher I., Schlenczek O., Schmidt J., Schroder M., Schwarzenboeck A., Sealy A., Senff C. J., Serikov I., Shohan S., Siddle E., Smirnov A., Spath F., Spooner B., Katharina Stolla M., Szkolka W., De Szoeke S. P., Tarot S., Tetoni E., Thompson E., Thomson J., Tomassini L., Totems J., Ubele A. A., Villiger L., Von Arx J., Wagner T., Walther A., Webber B., Wendisch M., Whitehall S., Wiltshire A., Wing A. A., Wirth M., Wiskandt J., Wolf K., Worbes L., Wright E., Wulfmeyer V., Young S., Zhang C., Zhang D., Ziemen F., Zinner T., and Zoger M.

Abstract

The science guiding the EUREC4A campaign and its measurements is presented. EUREC4A comprised roughly 5 weeks of measurements in the downstream winter trades of the North Atlantic - eastward and southeastward of Barbados. Through its ability to characterize processes operating across a wide range of scales, EUREC4A marked a turning point in our ability to observationally study factors influencing clouds in the trades, how they will respond to warming, and their link to other components of the earth system, such as upper-ocean processes or the life cycle of particulate matter. This characterization was made possible by thousands (2500) of sondes distributed to measure circulations on meso- (200 km) and larger (500 km) scales, roughly 400 h of flight time by four heavily instrumented research aircraft; four global-class research vessels; an advanced ground-based cloud observatory; scores of autonomous observing platforms operating in the upper ocean (nearly 10 000 profiles), lower atmosphere (continuous profiling), and along the air-sea interface; a network of water stable isotopologue measurements; targeted tasking of satellite remote sensing; and modeling with a new generation of weather and climate models. In addition to providing an outline of the novel measurements and their composition into a unified and coordinated campaign, the six distinct scientific facets that EUREC4A explored - from North Brazil Current rings to turbulence-induced clustering of cloud droplets and its influence on warm-rain formation - are presented along with an overview of EUREC4A's outreach activities, environmental impact, and guidelines for scientific practice. Track data for all platforms are standardized and accessible at 10.25326/165 , and a film documenting the campaign is provided as a video supplement.

Published
2021

18. Compliance with preoperative oral nutritional supplements in patients at nutritional risk--only a question of will?

Author

Grass, F., Bertrand, P.C., Schafer, M., Ballabeni, P., Cerantola, Y., Demartines, N., and Hubner, M.

Subjects
Patient compliance -- Research, Medical research, Dietary supplements -- Research, Food/cooking/nutrition, Health
Abstract

BACKGROUND/OBJECTIVES: Preoperative nutrition has been shown to reduce morbidity after major gastrointestinal (GI) surgery in selected patients at risk. In a randomized trial performed recently (NCT00512213), almost half of the patients, however, did not consume the recommended dose of nutritional intervention. The present study aimed to identify the risk factors for noncompliance. SUBJECTS/METHODS: Demographic (n = 5) and nutritional (n = 21) parameters for this retrospective analysis were obtained from a prospectively maintained database. The outcome of interest was compliance with the allocated intervention (ingestion of [greater than or equal to] 11/15 preoperative oral nutritional supplement units). Uni- and multivariate analyses of potential risk factors for noncompliance were performed. RESULTS: The final analysis included 141 patients with complete data sets for the purpose of the study. Fifty-nine patients (42%) were considered noncompliant. Univariate analysis identified low C-reactive protein levels (P =0.015), decreased recent food intake (P = 0.032) and, as a trend, low hemoglobin (P = 0.065) and low pre-albumin (P = 0.056) levels as risk factors for decreased compliance. However, none of them was retained as an independent risk factor after multivariate analysis. Interestingly, 17 potential explanatory parameters, such as upper GI cancer, weight loss, reduced appetite or co-morbidities, did not show any significant correlation with reduced intake of nutritional supplements. CONCLUSIONS: Reduced compliance with preoperative nutritional interventions remains a major issue because the expected benefit depends on the actual intake. Seemingly, obvious reasons could not be retained as valid explanations. Compliance seems thus to be primarily a question of will and information; the importance of nutritional supplementation needs to be emphasized by specific patients' education. European Journal of Clinical Nutrition (2015) 69, 525-529; doi: 10.1038/ejcn.2014.285; published online 21 January 2015, INTRODUCTION As up to 40% of surgical patients reveal preoperative impaired nutritional conditions, perioperative nutritional support has now been widely accepted as an adjunct of perioperative care. (1,2) There is [...]

Published
2015
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20. Rare coding variation provides insight into the genetic architecture and phenotypic context of autism

Author

J. M., Fu, Satterstrom, F. K., Peng, M., Brand, H., Collins, R. L., Dong, S., Wamsley, B., Klei, L., Wang, L., Hao, S. P., Stevens, C. R., Cusick, C., Babadi, M., Banks, E., Collins, B., Dodge, S., Gabriel, S. B., Gauthier, L., Lee, S. K., Liang, L., Ljungdahl, A., Mahjani, B., Sloofman, L., Smirnov, A. N., Barbosa, M., Betancur, C., Brusco, A., Chung, B. H. Y., Cook, E. H., Cuccaro, M. L., Domenici, E., Ferrero, G. B., Gargus, J. J., Herman, G. E., Hertz-Picciotto, I., Maciel, P., Manoach, D. S., Passos-Bueno, M. R., Persico, A., Renieri, A., Sutcliffe, J. S., Tassone, F., Trabetti, E., Campos, G., Cardaropoli, S., Carli, D., Chan, M. C. Y., Fallerini, C., Giorgio, E., Girardi, A. C., Hansen-Kiss, E., Lee, S. L., Lintas, C., Ludena, Y., Nguyen, R., Pavinato, L., Pericak-Vance, M., Pessah, I. N., Schmidt, R. J., Smith, M., Costa, C. I. S., Trajkova, S., Wang, J. Y. T., M. H. C., Yu, Aleksic, B., Artomov, M., Benetti, E., Biscaldi-Schafer, M., Borglum, A. D., Carracedo, A., Chiocchetti, A. G., Coon, H., Doan, R. N., Fernandez-Prieto, M., Freitag, C. M., Gerges, S., Guter, S., Hougaard, D. M., Hultman, C. M., Jacob, S., Kaartinen, M., Kolevzon, A., Kushima, I., Lehtimaki, T., Rizzo, C. L., Maltman, N., Manara, M., Meiri, G., Menashe, I., Miller, J., Minshew, N., Mosconi, M., Ozaki, N., Palotie, A., Parellada, M., Puura, K., Reichenberg, A., Sandin, S., Scherer, S. W., Schlitt, S., Schmitt, L., Schneider-Momm, K., Siper, P. M., Suren, P., Sweeney, J. A., Teufel, K., del Pilar Trelles, M., Weiss, L. A., Yuen, R., Cutler, D. J., De Rubeis, S., Buxbaum, J. D., Daly, M. J., Devlin, B., Roeder, K., Sanders, S. J., Talkowski, M. E., Massachusetts General Hospital [Boston], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Carnegie Mellon University [Pittsburgh] (CMU), Harvard Medical School [Boston] (HMS), University of California [San Francisco] (UC San Francisco), University of California (UC), University of California [Los Angeles] (UCLA), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Torino = University of Turin (UNITO), Azienda Ospedalerio - Universitaria Città della Salute e della Scienza di Torino = University Hospital Città della Salute e della Scienza di Torino, The University of Hong Kong (HKU), University of Illinois [Chicago] (UIC), University of Illinois System, University of Miami Leonard M. Miller School of Medicine (UMMSM), University of Trento [Trento], University of California [Irvine] (UC Irvine), Nationwide Children's Hospital, University of California [Davis] (UC Davis), Universidade do Minho = University of Minho [Braga], Massachusetts General Hospital [Boston, MA, USA], Escola Politecnica da Universidade de Sao Paulo [Sao Paulo], Università degli Studi di Messina = University of Messina (UniMe), Università degli Studi di Siena = University of Siena (UNISI), Azienda Ospedaliera Universitaria Senese, Vanderbilt University [Nashville], Vanderbilt University School of Medicine [Nashville], Università degli studi di Verona = University of Verona (UNIVR), University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome ( UCBM), Emory University School of Medicine, Emory University [Atlanta, GA], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Autism Sequencing Consortium (ASC), Broad Institute Center for Common Disease Genomics (Broad-CCDG), iPSYCH-BROAD Consortium : Branko Aleksic, Mykyta Artomov, Elisa Benetti, Monica Biscaldi-Schafer, Anders D Børglum, Angel Carracedo, Andreas G Chiocchetti, Hilary Coon, Ryan N Doan, Montserrat Fernández-Prieto, Christine M Freitag, Sherif Gerges, Stephen Guter, David M Hougaard, Christina M Hultman, Suma Jacob, Miia Kaartinen, Alexander Kolevzon, Itaru Kushima, Terho Lehtimäki, Caterina Lo Rizzo, Nell Maltman, Marianna Manara, Gal Meiri, Idan Menashe, Judith Miller, Nancy Minshew, Matthew Mosconi, Norio Ozaki, Aarno Palotie, Mara Parellada, Kaija Puura, Abraham Reichenberg, Sven Sandin, Stephen W Scherer, Sabine Schlitt, Lauren Schmitt, Katja Schneider-Momm, Paige M Siper, Pål Suren, John A Sweeney, Karoline Teufel, Maria Del Pilar Trelles, Lauren A Weiss, Ryan Yuen., and Betancur, Catalina

Subjects
Broad Institute Center for Common Disease Genomics, Autism Sequencing Consortium, DNA Copy Number Variations, Autism Spectrum Disorder, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Autism, Intellectual and Developmental Disabilities (IDD), iPSYCH-BROAD Consortium, autism spectrum disorders, disease gene, copy number variants, neuropsychiatric disorders, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, GENOMAS, Medical and Health Sciences, Article, Clinical Research, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Autistic Disorder, Aetiology, Genetic association study, Pediatric, Human Genome, Neurodevelopmental disorders, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Biological Sciences, Autism spectrum disorders, Brain Disorders, Mental Health, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Gene expression, Biotechnology, Developmental Biology
Abstract

International audience; Some individuals with autism spectrum disorder (ASD) carry functional mutations rarely observed in the general population. We explored the genes disrupted by these variants from joint analysis of protein-truncating variants (PTVs), missense variants and copy number variants (CNVs) in a cohort of 63,237 individuals. We discovered 72 genes associated with ASD at false discovery rate (FDR) ≤ 0.001 (185 at FDR ≤ 0.05). De novo PTVs, damaging missense variants and CNVs represented 57.5%, 21.1% and 8.44% of association evidence, while CNVs conferred greatest relative risk. Meta-analysis with cohorts ascertained for developmental delay (DD) (n = 91,605) yielded 373 genes associated with ASD/DD at FDR ≤ 0.001 (664 at FDR ≤ 0.05), some of which differed in relative frequency of mutation between ASD and DD cohorts. The DD-associated genes were enriched in transcriptomes of progenitor and immature neuronal cells, whereas genes showing stronger evidence in ASD were more enriched in maturing neurons and overlapped with schizophrenia-associated genes, emphasizing that these neuropsychiatric disorders may share common pathways to risk.

Published
2022

21. Policy documents and the beliefs of foreign policy decision-makers

Author

Bakker, F.E., Willigen, N.J.G. van, Schafer, M., Walker, S.G., Schafer, M., and Walker, S.G.

Abstract

As a psychological approach to foreign policy analysis, operational code analysis (OCA) has traditionally focused on individual leaders. In this chapter, we aim to expand the scope of OCA to the analysis of foreign policy and security documents. We argue that the beliefs of leaders impact their policy choices. We expect these beliefs to be reflected subsequently in the policy documents of their administrations. To test our argument, we compare the operational codes of US presidents Bush (43rd), Obama, and Trump with the operational codes of their administration's key foreign policy documents. The objective is to discover whether similar patterns exist between the operational codes of the US presidents and their policy papers. With this chapter, we aim to explore a new research avenue that can potentially allow us to better explain foreign policy-making. The chapter concludes with a reflection on the limits and opportunities of extending OCA to policy documents.

Published
2021

26. Genome-scale CRISPR Screens Identify Host Factors that Promote Human Coronavirus Infection

Author

Michael H. Norris, Roya Rafiee, Stephanie M. Karst, Chris D. Vulpe, Abderrahmane Tagmount, Amin Sobh, Schafer M, Andrew P. Bluhm, Max Russo, and Grodzki M

Subjects
medicine.drug_class, HEK 293 cells, Cell, Computational biology, Biology, biology.organism_classification, medicine.disease_cause, medicine.anatomical_structure, Pandemic, medicine, CRISPR, Human coronavirus OC43, Antiviral drug, Gene, Coronavirus
Abstract

The COVID-19 pandemic has resulted in 153 million infections and 3.2 million deaths as of May 2021. While effective vaccines are being administered globally, there is still a great need for antiviral therapies as potentially antigenically distinct SARS-CoV-2 variants continue to emerge across the globe. Viruses require host factors at every step in their life cycle, representing a rich pool of candidate targets for antiviral drug design. To identify host factors that promote SARS-CoV-2 infection with potential for broad-spectrum activity across the coronavirus family, we performed genome-scale CRISPR knockout screens in two cell lines (Vero E6 and HEK293T ectopically expressing ACE2) with SARS-CoV-2 and the common cold-causing human coronavirus OC43. While we identified multiple genes and functional pathways that have been previously reported to promote human coronavirus replication, we also identified a substantial number of novel genes and pathways. Of note, host factors involved in cell cycle regulation were enriched in our screens as were several key components of the programmed mRNA decay pathway. Finally, we identified novel candidate antiviral compounds targeting a number of factors revealed by our screens. Overall, our studies substantiate and expand the growing body of literature focused on understanding key human coronavirus-host cell interactions and exploit that knowledge for rational antiviral drug development.One Sentence SummaryGenome-wide CRISPR screens identified host factors that promote human coronavirus infection, revealing novel antiviral drug targets.

Published
2021

27. Innovative composite structural systems for modular tall buildings

Author

Knobloch, M, Kuhlmann, U, Kurz, W, Schafer, M, Thai, HT, Knobloch, M, Kuhlmann, U, Kurz, W, Schafer, M, and Thai, HT

Abstract

Modular or offsite construction is believed to shape the future of the construction industry as it possesses significant benefits over traditional onsite construction methods. However, most of its application are limited to steel or concrete buildings. Although steel-concrete composite structural system has many merits over the steel and concrete systems, its application in modular buildings is very limited. This paper explores recent developments of composite systems for modular high-rise buildings. They include modular units for resisting vertical gravity loads and lateral structural systems for resisting horizontal forces from wind and earthquake loadings and progressive collapse due to accidental loads such as fire, explosions and impact. Various inter-module joining methods developed in the literature will also be reviewed. Finally, a case study of the most efficient connection is presented to explore its applicability to high-rise modular buildings.

Published
2021

28. Early sedation with dexmedetomidine in ventilated critically ill patients and heterogeneity of treatment effect in the SPICE III randomised controlled trial.

Author

Abidin H.Z., Hassan M.H., Omar S.C., Shukeri W.F.W., Brealey D., Bercades G., Blackburn E., Macallum N., Macklin A., Ryu J.H., Tam K., Smyth D., Arif A., Bassford C., Morgan C., Swann C., Ward G., Wild L., Bone A., Elderkin T., Green D., Sach D., Salerno T., Simpson N., Brohi F., Clark M., Williams L., Brooks J., Cocks E., Cole J., Curtin J., Davies R., Hill H., Morgan M., Palmer N., Whitton C., Wise M., Baskaran P., Hasan M.S., Tham L.Y., Cruz R.S., Dinsdale D., Edney S., Firkin C., FitzJohn F., Hill G., Hunt A., Hurford S., Jones G., Judd H., Latimer-Bell C., Lawrence C., Lesona E., Navarra L., Robertson Y., Smellie H., Vucago A.M., Young P., Dawson H., Griffith D.M., Paterson R., Clark P., Kong J., Ho J., Nayyar V., Skelly C., Shehabi Y., Serpa Neto A., Howe B.D., Arabi Y.M., Bass F.E., Kadiman S.B., McArthur C.J., Reade M.C., Seppelt I.M., Wise M.P., Mashonganyika C., McKee H., Tonks A., Donnelly A., Hemmings N., O'Kane S., Blakemore A., Butler M., Cowdrey K., Dalton J., Gilder E., Long S., McCarthy L., McGuinness S., Parke R., Chen Y., McArthur C., McConnochie R., Newby L., Bellomo R., Eastwood G., Peck L., Young H., Boschert C., Edington J., Fletcher J., Nand K., Raza A., Sara T., Bennett-Britton J., Bewley J., Bodenham V., Cole L., Driver K., Grimmer L., Howie L., Searles C., Sweet K., Webster D., van Berkel A., Connor H., Dennett J., van Der Graaff M., Henderson S., Mehrtens J., Miller K., Minto E., Morris A., Noble S., Parker K., Hart N., Shepherd K., Vij S., Dickson S., Elloway E., Ferguson C., Jackson R., MacNaughton P., Marner M., Squire R., Waddy S., Wafer P., Welbourne J., Ashcroft P., Chambler D., Dukes S., Harris A., Horton S., Sharpe S., Williams P., Williams S., Bailey M., Blazquez E., France D., Hutchison R., Comadira G., Gough M., Tallott M., Bastick M., Cameron R., Donovan S., Gaur A., Gregory R., Naumoff J., Turner E., White M., Au K.F.J., Fratzia J., Treloar S., Lim C.H., Maseeda Y., Tan A.P., Tang C.L., Yong C.Y., Akaltan M., Berger S., Blaser D., Fazlija L., Jong M.L., Lensch M., Ludwig R., Merz T., Nettelbeck K., Roth M., Schafer M., Takala J., Wehr A., Zacharias D., Amran R., Ashraf H.N., Azmi N., Basri N., Burhanuddin H., Hadinata Y., Hamdan A., Kadiman S., Rashid A.I.Y.M., Sabran I.N., Sulaiman S., Zabidi I.N., Al-Dawood A., Aljuaid M., Al Anizi H., Al Saeedi A., Arabi Y., Dbsawy M., Deeb A., Hegazy M., Magdi I., Corcoran E., Finney C., Dumlao L.A., Bassam R., Hassan M.A., Naseem N., Al-Kurdi M.H., Al-Harthy A.M., Bernard S., Sebafundi L., Serban C., Lim S.K., Mazidah N., Saidin N., Sjamsuddin N., Tan I.T.A., Zabidi N., Brain M., Mineall S., Kanhere M., Soar N., Kadir N.A., Abdullah N.H., Awang R., Emperan Z., Husin N.S., Ismail N.I., Ismail S.Z., Khadzali F.N.A.M., Norddin M.F., Aguila J., Bold C., Clatworthy B., Dias A., Hogan C., Kazemi A., Lai V., Song R., Williams A., Bhatia D., Bulfin L., Elliot S., Galt P., Lavrans K., Ritchie P., Wang A., Gresham R., Lowrey J., Masters K., Palejs P., Seppelt I., Symonds F., Weisbrodt L., Whitehead C., Babio-Galan M., Calder V., Clement I., Harrison A., McCullagh I., Scott C., Bevan R., Caniba S., Hacking D., Maher L., Azzolini M.L., Beccaria P., Colombo S., Landoni G., Leggieri C., Luca C., Mamo D., Moizo E., Monti G., Mucci M., Zangrillo A., Albania M., Arora S., Shi Y., Abudayah A., Almekhlafi G., Al Amodi E., Al Samarrai S., Badawi M., Caba R.C., Elffaki O., Mandourah Y., Valerio J., Joyce C., Meyer J., Saylor E., Venkatesh B., Venz E., Walsham J., Wetzig K., Clarey E., Harris C., Hopkins P., Noble H., Thompson L., Williams T., Khoo T.M., Liew J.E.S., Sakthi A.N., Zulkurnain A., Bamford A., Bergin C., Carrera R., Cooper L., Despy L., Ellis K., Harkett S., Mee L., Reeves E., Snelson C., Spruce E., Cooper G., Hodgson R., Pearson D., Rosbergen M., Ali M.N., Bahar N.I., Ismail A., Ismail W.N.W., Samat N.M., Piah N.S.M., Rahman R.A., Duroux M., Ratcliffe M., Warhurst T., Buehner U., Williams E., Jacques N., Keating L., Macgill S., Tamang K.L., Tolan N., Walden A., Bower R., Cranshaw J., Molloy K., Pitts S., Butler J., Dunlop R., Fourie C., Jarrett P., Lassig-Smith M., Livermore A., O'Donoghue S., Reade M., Starr T., Stuart J., Campbell L., Phillips M., Stephens D., Thomas J., Cooper D., McAllister R., Andrew G., Barclay L., Hope D., Wojcik G., McCulloch C., Ascough L., Paisley C., Patrick-Heselton J., Shaw D., Waugh V., Williams K., Welters I., Barge D., Jordan A., MacIsaac C., Rechnitzer T., Bass F., Gatward J., Hammond N., Janin P., O'Connor A., Stedman W., Yarad E., Razak N.A., Dzulkipli N., Jong S.L., Asen K., Voon W.L., Liew S., Ball J., Barnes V., Dalton C., Farnell-Ward S., Farrah H., Maher K., Mellinghoff J., Ryan C., Shirley P., Conlon L., Glover A., Martin-Loeches I., O'Toole E., Ewan J., Ferrier J., Litton E., Webb S.A., Berry W., Alonso U.B., Bociek A., Campos S., Jawara S., Hanks F., Kelly A., Lei K., McKenzie C., Ostermann M., Wan R., Al-Soufi S., Leow S., McCann K., Reynolds C., Brickell K., Fahey C., Hays L., Hyde N., Nichol A., Ryan D., Brailsford J., Buckley A., Forbes L., Maguire T., Moore J., Murray L., Ghosh A., Park M., Said S., Smith J., Visser A., Ali S., Abidin H.Z., Hassan M.H., Omar S.C., Shukeri W.F.W., Brealey D., Bercades G., Blackburn E., Macallum N., Macklin A., Ryu J.H., Tam K., Smyth D., Arif A., Bassford C., Morgan C., Swann C., Ward G., Wild L., Bone A., Elderkin T., Green D., Sach D., Salerno T., Simpson N., Brohi F., Clark M., Williams L., Brooks J., Cocks E., Cole J., Curtin J., Davies R., Hill H., Morgan M., Palmer N., Whitton C., Wise M., Baskaran P., Hasan M.S., Tham L.Y., Cruz R.S., Dinsdale D., Edney S., Firkin C., FitzJohn F., Hill G., Hunt A., Hurford S., Jones G., Judd H., Latimer-Bell C., Lawrence C., Lesona E., Navarra L., Robertson Y., Smellie H., Vucago A.M., Young P., Dawson H., Griffith D.M., Paterson R., Clark P., Kong J., Ho J., Nayyar V., Skelly C., Shehabi Y., Serpa Neto A., Howe B.D., Arabi Y.M., Bass F.E., Kadiman S.B., McArthur C.J., Reade M.C., Seppelt I.M., Wise M.P., Mashonganyika C., McKee H., Tonks A., Donnelly A., Hemmings N., O'Kane S., Blakemore A., Butler M., Cowdrey K., Dalton J., Gilder E., Long S., McCarthy L., McGuinness S., Parke R., Chen Y., McArthur C., McConnochie R., Newby L., Bellomo R., Eastwood G., Peck L., Young H., Boschert C., Edington J., Fletcher J., Nand K., Raza A., Sara T., Bennett-Britton J., Bewley J., Bodenham V., Cole L., Driver K., Grimmer L., Howie L., Searles C., Sweet K., Webster D., van Berkel A., Connor H., Dennett J., van Der Graaff M., Henderson S., Mehrtens J., Miller K., Minto E., Morris A., Noble S., Parker K., Hart N., Shepherd K., Vij S., Dickson S., Elloway E., Ferguson C., Jackson R., MacNaughton P., Marner M., Squire R., Waddy S., Wafer P., Welbourne J., Ashcroft P., Chambler D., Dukes S., Harris A., Horton S., Sharpe S., Williams P., Williams S., Bailey M., Blazquez E., France D., Hutchison R., Comadira G., Gough M., Tallott M., Bastick M., Cameron R., Donovan S., Gaur A., Gregory R., Naumoff J., Turner E., White M., Au K.F.J., Fratzia J., Treloar S., Lim C.H., Maseeda Y., Tan A.P., Tang C.L., Yong C.Y., Akaltan M., Berger S., Blaser D., Fazlija L., Jong M.L., Lensch M., Ludwig R., Merz T., Nettelbeck K., Roth M., Schafer M., Takala J., Wehr A., Zacharias D., Amran R., Ashraf H.N., Azmi N., Basri N., Burhanuddin H., Hadinata Y., Hamdan A., Kadiman S., Rashid A.I.Y.M., Sabran I.N., Sulaiman S., Zabidi I.N., Al-Dawood A., Aljuaid M., Al Anizi H., Al Saeedi A., Arabi Y., Dbsawy M., Deeb A., Hegazy M., Magdi I., Corcoran E., Finney C., Dumlao L.A., Bassam R., Hassan M.A., Naseem N., Al-Kurdi M.H., Al-Harthy A.M., Bernard S., Sebafundi L., Serban C., Lim S.K., Mazidah N., Saidin N., Sjamsuddin N., Tan I.T.A., Zabidi N., Brain M., Mineall S., Kanhere M., Soar N., Kadir N.A., Abdullah N.H., Awang R., Emperan Z., Husin N.S., Ismail N.I., Ismail S.Z., Khadzali F.N.A.M., Norddin M.F., Aguila J., Bold C., Clatworthy B., Dias A., Hogan C., Kazemi A., Lai V., Song R., Williams A., Bhatia D., Bulfin L., Elliot S., Galt P., Lavrans K., Ritchie P., Wang A., Gresham R., Lowrey J., Masters K., Palejs P., Seppelt I., Symonds F., Weisbrodt L., Whitehead C., Babio-Galan M., Calder V., Clement I., Harrison A., McCullagh I., Scott C., Bevan R., Caniba S., Hacking D., Maher L., Azzolini M.L., Beccaria P., Colombo S., Landoni G., Leggieri C., Luca C., Mamo D., Moizo E., Monti G., Mucci M., Zangrillo A., Albania M., Arora S., Shi Y., Abudayah A., Almekhlafi G., Al Amodi E., Al Samarrai S., Badawi M., Caba R.C., Elffaki O., Mandourah Y., Valerio J., Joyce C., Meyer J., Saylor E., Venkatesh B., Venz E., Walsham J., Wetzig K., Clarey E., Harris C., Hopkins P., Noble H., Thompson L., Williams T., Khoo T.M., Liew J.E.S., Sakthi A.N., Zulkurnain A., Bamford A., Bergin C., Carrera R., Cooper L., Despy L., Ellis K., Harkett S., Mee L., Reeves E., Snelson C., Spruce E., Cooper G., Hodgson R., Pearson D., Rosbergen M., Ali M.N., Bahar N.I., Ismail A., Ismail W.N.W., Samat N.M., Piah N.S.M., Rahman R.A., Duroux M., Ratcliffe M., Warhurst T., Buehner U., Williams E., Jacques N., Keating L., Macgill S., Tamang K.L., Tolan N., Walden A., Bower R., Cranshaw J., Molloy K., Pitts S., Butler J., Dunlop R., Fourie C., Jarrett P., Lassig-Smith M., Livermore A., O'Donoghue S., Reade M., Starr T., Stuart J., Campbell L., Phillips M., Stephens D., Thomas J., Cooper D., McAllister R., Andrew G., Barclay L., Hope D., Wojcik G., McCulloch C., Ascough L., Paisley C., Patrick-Heselton J., Shaw D., Waugh V., Williams K., Welters I., Barge D., Jordan A., MacIsaac C., Rechnitzer T., Bass F., Gatward J., Hammond N., Janin P., O'Connor A., Stedman W., Yarad E., Razak N.A., Dzulkipli N., Jong S.L., Asen K., Voon W.L., Liew S., Ball J., Barnes V., Dalton C., Farnell-Ward S., Farrah H., Maher K., Mellinghoff J., Ryan C., Shirley P., Conlon L., Glover A., Martin-Loeches I., O'Toole E., Ewan J., Ferrier J., Litton E., Webb S.A., Berry W., Alonso U.B., Bociek A., Campos S., Jawara S., Hanks F., Kelly A., Lei K., McKenzie C., Ostermann M., Wan R., Al-Soufi S., Leow S., McCann K., Reynolds C., Brickell K., Fahey C., Hays L., Hyde N., Nichol A., Ryan D., Brailsford J., Buckley A., Forbes L., Maguire T., Moore J., Murray L., Ghosh A., Park M., Said S., Smith J., Visser A., and Ali S.

Abstract

Purpose: To quantify potential heterogeneity of treatment effect (HTE), of early sedation with dexmedetomidine (DEX) compared with usual care, and identify patients who have a high probability of lower or higher 90-day mortality according to age, and other identified clusters. Method(s): Bayesian analysis of 3904 critically ill adult patients expected to receive invasive ventilation > 24 h and enrolled in a multinational randomized controlled trial comparing early DEX with usual care sedation. Result(s): HTE was assessed according to age and clusters (based on 12 baseline characteristics) using a Bayesian hierarchical models. DEX was associated with lower 90-day mortality compared to usual care in patients > 65 years (odds ratio [OR], 0.83 [95% credible interval [CrI] 0.68-1.00], with 97.7% probability of reduced mortality across broad categories of illness severity. Conversely, the probability of increased mortality in patients = 65 years was 98.5% (OR 1.26 [95% CrI 1.02-1.56]. Two clusters were identified: cluster 1 (976 patients) mostly operative, and cluster 2 (2346 patients), predominantly non-operative. There was a greater probability of benefit with DEX in cluster 1 (OR 0.86 [95% CrI 0.65-1.14]) across broad categories of age, with 86.4% probability that DEX is more beneficial in cluster 1 than cluster 2. Conclusion(s): In critically ill mechanically ventilated patients, early sedation with dexmedetomidine exhibited a high probability of reduced 90-day mortality in older patients regardless of operative or non-operative cluster status. Conversely, a high probability of increased 90-day mortality was observed in younger patients of non-operative status. Further studies are needed to confirm these findings.Copyright © 2021, Crown.

Published
2021

29. Preoperative immunonutrition in patients at nutritional risk: results of a double-blinded randomized clinical trial

Author

Hubner, M., Cerantola, Y., Grass, F., Bertrand, P.C., Schafer, M., and Demartines, N.

Subjects
Parenteral feeding -- Research, Parenteral therapy -- Research, Abdominal surgery -- Research, Hospital patients -- Food and nutrition, Food/cooking/nutrition, Health
Abstract

BACKGROUND/OBJECTIVES: To evaluate the impact of preoperative immunonutrition (IN) on postoperative morbidity in patients at risk of malnutrition undergoing major gastrointestinal (GI) surgery. SUBJECTS/METHODS: The combination of malnutrition and major GI surgery entails high morbidity. The Nutritional Risk Score (NRS) reliably identifies patients who need preoperative nutrition; the optimal nutritional formula for these patients still needs to be defined. In all, 152 patients with a NRSX3 and undergoing elective major GI surgery were randomized between IN or isocaloricisonitrogenous nutrition (ICN) given for 5 days preoperatively. Patients and caregivers were blinded for the allocated intervention. Thirty days complication rate was the primary endpoint. Infections, length of hospital stay and compliance were considered as secondary outcomes. RESULTS: Overall, 145 patients were available for analysis; the 73 patients in the IN group matched well with the 72 ICN patients with regards to patient's and surgical characteristics. In all, 39 IN and 33 ICN patients experienced a total of 48 and 50 postoperative complications, respectively (P = 0.723). Both groups did not differ significantly concerning infectious (13 vs 9) complications. Independent risk factors for overall complications were malignant disease (odds ratio (OR) = 4.304; confidence interval (CI) 1.317-14.002) and operative time (OR = 1.004;CI 1.000-1.008). CONCLUSION: In patients at nutritional risk, complications, infections and hospital stay after major GI surgery were comparable regardless of preoperative supplementation with IN or ICN. European Journal of Clinical Nutrition (2012) 66, 850-855; doi: 10.1038/ejcn.2012.53; published online 23 May 2012 Keywords: abdominal surgery; immunonutrition; complications; compliance, INTRODUCTION Careful perioperative risk reduction in patients undergoing major gastrointestinal (GI) surgery is an evolving key concept to decrease postoperative morbidity rates, which range from 35 to 50%.1-3 Many risk [...]

Published
2012
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30. Perioperative nutrition is still a surgical orphan: results of a Swiss-Austrian survey

Author

Grass, F., Cerantola, Y., Schafer, M., Muller, S., Demartines, N., and Hubner, M.

Subjects
Nutrition -- Surveys -- Nutritional aspects, Surgical clinics -- Surveys -- Nutritional aspects, Perioperative care -- Nutritional aspects -- Surveys, Medical screening -- Surveys -- Nutritional aspects, Food/cooking/nutrition, Health
Abstract

Background/Objectives: There is strong evidence for the beneficial effects of perioperative nutrition in patients undergoing major surgery. We aimed to evaluate implementation of current guidelines in Switzerland and Austria. Subjects/Methods: A survey was conducted in 173 Swiss and Austrian surgical departments. We inquired about nutritional screening, perioperative nutrition and estimated clinical significance. Results: The overall response rate was 55%, having 69% (54/78) responders in Switzerland and 44% (42/95) in Austria. Most centres were aware of reduced complications (80%) and shorter hospital stay (59%). However, only 20% of them implemented routine nutritional screening. Non-compliance was because of financial (49%) and logistic restrictions (33%). Screening was mainly performed in the outpatient's clinic (52%) or during admission (54%). The nutritional risk score was applied by 14% only; instead, various clinical (78%) and laboratory parameters (56%) were used. Indication for perioperative nutrition was based on preoperative screening in 49%. Although 23% used preoperative nutrition, 68% applied nutritional support pre- and postoperatively. Preoperative nutritional treatment ranged from 3 days (33%), to 5 (31%) and even 7 days (20%). Conclusions: Although malnutrition is a well-recognised risk factor for poor post-operative outcome, surgeons remain reluctant to implement routine screening and nutritional support according to evidence-based guidelines. European journal of Clinical Nutrition (2011) 65, 642-647; doi: 10.1038/ejcn.2011.13; published online 23 February 2011 Keywords: immune enhancing; immunonutrition; screening; surgery; complications; infections, Introduction Major gastrointestinal (GI) surgery can nowadays be performed with a low mortality, but complex surgical procedures are still associated with increased post-operative complication rates. This is particularly related to [...]

Published
2011
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32. Opposite effect of cAMP signaling in endothelial barriers of different origin

Author

Bindewald, K., Gunduz, D., Hartel, F., Peters, S.C., Rodewald, C., Nau, S., Schafer, M., Neumann, J., Piper, H.M., and Noll, T.

Subjects
Myosin -- Research, Cells -- Research, Endothelium -- Research, Biological sciences
Abstract

Opposite effect of cAMP signaling in endothelial barriers of different origin. Am J Physiol Cell Physiol 287: C1246-C1255, 2004; doi: 10.1152/ajpcell.00132.2004.--cAMP-mediated signaling mechanisms may destabilize or stabilize the endothelial barrier, depending on the origin of endothelial cells. Here, microvascular coronary [coronary endothelial cells (CEC)] and macrovascular aortic endothelial cell (AEC) monolayers with opposite responses to cAMP were analyzed. Macromolecule permeability, isometric force, activation state of contractile machinery [indicated by phosphorylation of regulatory myosin light chains (MLC), activity of MLC kinase, and MLC phosphatase], and dynamic changes of adhesion complex proteins (translocation of VE-cadherin and paxillin) were determined, cAMP signaling was stimulated by the adenosine receptor agonist 5'-N-(ethylcarboxamido)-adenosine (NECA), the [beta]-adrenoceptor agonist isoproterenol (Iso), or by the adenylyl cyclase activator forskolin (FSK). Permeability was increased in CEC and decreased in AEC on stimulation with NECA, Iso, or FSK. The effects could be inhibited by the PKA inhibitor Rp-8-CPT-cAMPS and imitated by the PKA activator Sp-cAMPS. Under cAMP/PKA-dependent stimulation, isometric force and MLC phosphorylation were reduced in monolayers of either cell type, due to an activation of MLC phosphatase. In CEC but not in AEC, FSK induced delocalization of VE-cadherin and paxillin from cellular adhesion complexes as indicated by cell fractionation and immunofluorescence microscopy. In conclusion, decline in contractile activation and isometric force contribute to cAMP/PKA-mediated stabilization of barrier function in AEC. In CEC, this stabilizing effect is overruled by cAMP-induced disintegration of cell adhesion structures. endothelial cell adhesion; endothelial permeability; isometric force; myosin light chain kinase; myosin light chain pbosphatase

Published
2004

33. MEK/MAPK as a signaling element in ATP control of endothelial myosin light chain

Author

Klingenberg, D., Gunduz, D., Hartel, F., Bindewald, K., Schafer, M., Piper, H.M., and Noll, T.

Subjects
Protein kinases -- Research, Biological sciences
Abstract

Klingenberg, D., D. Gunduz, F. Hartel, K. Bindewald, M. Schafer, H. M. Piper, and T. Noll. MEK/MAPK as a signaling element in ATP control of endothelial myosin light chain. Am J Physiol Cell Physiol 286: C807-C812, 2004; 10.1152/ajpcell.00002.2003.--Phosphorylation of endothelial myosin light chains (MLC) is a key mechanism in control of endothelial contractile machinery. Extracellular ATP influences endothelial MLC phosphorylation by either activation of [Ca.sup.2+] -dependent MLC kinase or [Ca.sup.2+]-independent MLC phosphatase. Here, the role of the MEK/MAPK pathway in this signaling was investigated in porcine aortic endothelial cells. Phosphorylation of ERK2 and phosphorylation of MLC were analyzed in cultured aortic endothelial cells. ATP (10 [micro]M) increased ERK2 phosphorylation from basal 17 [+ or -] 3 to 53 [+ or -] 4%, an effect suppressed in the presence of the MEK inhibitors PD-98059 (20 [micro]M) or U0126 (10 [micro]M). Phosphorylation of ERK2 was not dependent on the ATP-induced cytosolic [Ca.sup.2+] rise, because it was unaltered when this was suppressed by the [Ca.sup.2+] chelator BAPTA (10 [micro]M) or xestospongin C (3 [micro]M), an inhibitor of the inositol 1,4,5 trisphosphate-sensitive [Ca.sup.2+] release mechanism of the endoplasmic reticulum. Phosphorylation of ERK2 was neither induced by the adenosine analog 5'-(N-ethylcarboxamido)adenosine (l [micro]M) nor inhibited in the presence of the adenosine receptor antagonist 8-phenyltheophylline (10 [micro]M). ATP increased MLC kinase activity, and this was blocked in presence of PD-98059. ATP also increased MLC phosphatase activity, which was not inhibited by PD-98059. The MEK/MAPK pathway is a [Ca.sup.2+] -independent part of ATP signaling toward MLC kinase but not of ATP signaling toward MLC phosphatase. mitogen-activated protein kinase; contractile machinery; myosin light chain kinase; myosin light chain phosphatase

Published
2004

34. The genome sequence of Schizosaccharomyces pombe

Author

Wood, V., Gwilliam, R., Rajandream, M.-A., Lyne, M., Lyne, R., Stewart, A., Sgouros, J., Peat, N., Hayles, J., Baker, S., Basham, D., Bowman, S., Brooks, K., Brown, D., Brown, S., Chillingworth, T., Churcher, C., Collins, M., Connor, R., Cronin, A., Davis, P., Feltwell, T., Fraser, A., Gentles, S., Goble, A., Hamlin, N., Harris, D., Hidalgo, J., Hodgson, G., Holroyd, S., Hornsby, T., Howarth, S., Huckle, E. J., Hunt, S., Jagels, K., James, K., Jones, L., Jones, M., Leather, S., McDonald, S., McLean, J., Mooney, P., Moule, S., Mungall, K., Murphy, L., Niblett, D., Odell, C., Oliver, K., O'Neil, S., Pearson, D., Quail, M. A., Rabbinowitsch, E., Rutherford, K., Rutter, S., Saunders, D., Seeger, K., Sharp, S., Skelton, J., Simmonds, M., Squares, R., Squares, S., Stevens, K., Taylor, K., Taylor, R. G., Tivey, A., Walsh, S., Warren, T., Whitehead, S., Woodward, J., Volckaert, G., Aert, R., Robben, J., Grymonprez, B., Weltjens, I., Vanstreels, E., Rieger, M., Schafer, M., Muller-Auer, S., Gabel, C., Fuchs, M., Fritzc, C., Holzer, E., Moestl, D., Hilbert, H., Borzym, K., Langer, I., Beck, A., Lehrach, H., Reinhardt, R., Pohl, T. M., Eger, P., Zimmermann, W., Wedler, H., Wambutt, R., Purnelle, B., Goffeau, A., Cadieu, E., Dreano, S., Gloux, S., Lelaure, V., Mottier, S., Galibert, F., Aves, S. J., Xiang, Z., Hunt, C., Moore, K., Hurst, S. M., Lucas, M., Rochet, M., Gaillardin, C., Tallada, V. A., Garzon, A., Thode, G., Daga, R. R., Cruzado, L., Jimenez, J., Sanchez, M., del Rey, F., Benito, J., Dominguez, A., Revuelta, J. L., Moreno, S., Armstrong, J., Forsburg, S. L., Cerrutti, L., Lowe, T., McCombie, W. R., Paulsen, I., Potashkin, J., Shpakovski, G. V., Ussery, D., Barrell, B. G., and Nurse, P.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): V. Wood [1]; R. Gwilliam [1]; M.-A. Rajandream (corresponding author) [1]; M. Lyne [1]; R. Lyne [1]; A. Stewart [2]; J. Sgouros [2]; N. Peat [3]; J. Hayles [3]; [...]

Published
2002
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38. Vanadium interferes with siderophore-mediated iron uptake in Pseudomonas aeruginosa

Author

Baysse, C., De Vos, D., Naudet, Y., Vandermonde, A., Meyer, J.-M., Budzikiewicz, H., Fuchs, R., Cornelis, P., Schafer, M., and Ochsner, U.

Subjects
Bacteria -- Physiological aspects, Vanadium -- Physiological aspects, Cytochemistry -- Research, Pseudomonas aeruginosa -- Physiological aspects, Iron -- Physiological aspects, Biological sciences
Abstract

Vanadium has been found to interfere with siderophore-mediated iron uptake in Pseudomonas aeruginosa. V-pyochelin (PCH) catalyses a Fenton-type reaction in which the toxic superoxide anion O(sub.2)(super.-) is generated. PCH-negative mutants were seen to be more resistant to vanadium than the wild-type strain.

Published
2000

41. Dispersion and feeding ecology of wintering cormorants

Author

Schafer, M. M.

Subjects
591.7
Abstract

The dispersion of wintering cormorants (Phalacrocorax carbo) was studied in an estuarine habitat in northeast Scotland. Birds were dispersed in mobile clumps both when roosting and when foraging. A cormorant's choice of roosting site appeared to be influenced primarily by the nature of the site, but the use of decoys showed that groups arose on suitable sites by social attraction. There was evidence that the communal roost had survival value as an antipredator strategy. The use of decoys demonstrated that foraging clumps arose through social attraction. Cormorants also followed each other from the communal roost to the foraging grounds. It was concluded that the roost acts as an "information centre" in extending the benefits of social foraging by local enhancement in food-finding. Individual foraging success was not influenced significantly by tidal variations or water-roughness and associated turbidities, but success was higher around midday than at other times of day and most birds foraged around this time. Individual foraging success was not affected by the number of birds foraging but rose significantly with increasing clumping. Adult cormorants were more successful than juveniles and captured larger fish. Foraging in tight groups was thought to be more advantageous to the more inexperienced juvenile birds in reducing the risk of no success compared to foraging other than in groups or alone. The enhanced feeding success of birds in clumps was considered to be a consequence of groups arising in the best foraging areas through local enhancement rather than a result of birds in groups behaving differently from non-group foragers. The dispersion in loose flocks was seen as a strategy for successful exploitation of non-shoaling cryptic prey dispersed in unpredictably located patches.

Published
1982

42. Immobilized photosensitizers for solar photochemical applications

Author

Faust, D., Funken, K.-H., Horneck, G., Milow, B., Ortner, J., Sattlegger, M., Schafer, M., and Schmitz, C.

Subjects
Photosensitizing compounds -- Research, Solar thermal energy -- Research, Solar energy research -- Analysis, Photochemical research -- Analysis, Earth sciences, Petroleum, energy and mining industries
Abstract

New hydrophilic immobilized photosensitizers (heterogeneous phase) were synthesized that overcome some disadvantages of the use of homogeneous phase sensitizers for detoxification and disinfection of water. The chosen sensitizers, based on porphyrin moieties, were bound on poly(methyl methacrylate) (PMMA). The measured production rate of singlet oxygen is significantly higher than that of the well-known rose bengal immobilized on Merrifield polymer. The sensitive polymer can be used for detoxification and disinfection of polluted water.

Published
1999

45. Statement on imaging and pulmonary hypertension from the Pulmonary Vascular Research Institute (PVRI)

Author

Kiely, D., Levin, D., Hassoun, P., Ivy, D.D., Jone, P.-N., Bwika, J., Kawut, S.M., Lordan, J., Lungu, A., Mazurek, J., Moledina, S., Olschewski, H., Peacock, A., Puri, G.D., Rahaghi, F., Schafer, M., Schiebler, M., Screaton, N., Tawhai, M., Van Beek, E.J., Vonk-Noordegraaf, A., Vanderpool, R.R., Wort, J., Zhao, L., Wild, J., Vogel-Claussen, J., and Swift, A.

Subjects
cardiac catheterization, algorithm, diagnosis, pulmonary hypertension, education, Consensus Report, imaging, magnetic resonance imaging, echocardiography, computed tomography, guidelines
Abstract

Pulmonary hypertension (PH) is highly heterogeneous and despite treatment advances it remains a life-shortening condition. There have been significant advances in imaging technologies, but despite evidence of their potential clinical utility, practice remains variable, dependent in part on imaging availability and expertise. This statement summarizes current and emerging imaging modalities and their potential role in the diagnosis and assessment of suspected PH. It also includes a review of commonly encountered clinical and radiological scenarios, and imaging and modeling-based biomarkers. An expert panel was formed including clinicians, radiologists, imaging scientists, and computational modelers. Section editors generated a series of summary statements based on a review of the literature and professional experience and, following consensus review, a diagnostic algorithm and 55 statements were agreed. The diagnostic algorithm and summary statements emphasize the key role and added value of imaging in the diagnosis and assessment of PH and highlight areas requiring further research.

Published
2019

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