Author: "Marcus, J." / Publication Type: Electronic Resources - Searchworks@Jio Institute Digital Library Search Results

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932 results on '"Marcus, J."'

1. Design and operation of a metal hydride reactor within a thermochemical energy store for use in concentrated solar power

Author: Adams, Marcus J.
Subjects: 621.47, TJ Mechanical engineering and machinery
Abstract: This thesis covers the design of a metal hydride reactor within a thermo-chemical energy store for use in concentrated solar power (CSP). Thermo-chemical energy storage has been explored to improve on existing sensible heat technologies, potentially enabling fulfilment of CSP thermal energy storage cost targets, where metal hydrides have emerged as a TCES front-runner. This work introduces a unifying model for both the hydrogenation and dehydrogenation kinetics of MgH2, through the Site Availability Model (SAM). The model expands on Langmuir's site theory, in which a site can also be unavailable or available to react. This "unavailability" is governed by the site availability driving force, incorporating ideas such as site de-activation and strain/relaxation, which is influenced by temperature and pressure. These phenomena are proposed for both hydrogenation and dehydrogenation. In addition, SAM assumes the rate determining step is at the surface, where both hydrogenation/dehydrogenation assume a spherical surface, with dehydrogenation including the concept of particle fragmentation. The models developed, SAM:DR and SAM:ACR:SC:F, were successful in representing the kinetics of Mg hydrogenation and MgH2 dehydrogenation respectively of a small 0.2g sample, for all conditions tested. This includes conditions at close and moderately far from equilibrium for Mg hydrogenation. The SAM was also successfully applied to a 154g magnesium sample, providing confidence that the derived rate laws exhibit intensive characteristics, and assurance that the models can be used for larger scale reactor design. The implications of the thesis demonstrate the advancement in reactor design for metal hydride thermo-chemical energy storage to enable larger scale reactor designs. N.B. COVID-19 did not majorly impact the project completion, however it did disrupt the experiments on the large lab-scale reactor (chapter 6). The duration of the delay was approximately 3-4 months. It would have been desirable to run more tests and explore ways to achieve a higher operating temperature. In general, it was possible to fulfil the aims and objectives of this thesis.
Published: 2021

2. Modelling blue-light ambulance mobility in the London metropolitan area

Author: Poulton, Marcus J.
Subjects: 362.18
Abstract: Actions taken immediately following a life-threatening incident are critical for the survival of the patient. In particular, the timely arrival of ambulance crew often makes the difference between life and death. As a consequence, ambulance services are under persistent pressure to achieve rapid emergency response. Meeting stringent performance requirements poses special challenges in metropolitan areas where the higher population density results in high rates of life-threatening incident occurrence, compounded by lower response speeds due to traffic congestion. A key ingredient of data-driven approaches to address these challenges is the effective modelling of ambulance movement thus enabling the accurate prediction of the expected arrival time of a crew at the site of an incident. Ambulance mobility patterns however are distinct and in particular differ from civilian traffic: crews travelling with ashing blue lights and sirens are by law exempt from certain traffic regulations; and moreover, ambulance journeys are triggered by emergency incidents that are generated following distinct spatial and temporal patterns. We use a large historical dataset of incidents and ambulance location traces to model route selection and arrival times. Working on a road routing network modified to reflect the differences between emergency and regular vehicle traffic, we develop a methodology for matching ambulances Global Positioning System (GPS) coordinates to road segments, allowing the reconstruction of ambulance routes with precise speed data. We demonstrate how a road speed model that exploits this information achieves best predictive performance by implicitly capturing route-specific patterns in changing traffic conditions. We then present a hybrid model that achieves a high route similarity score while minimising journey duration error. This hybrid model outperforms alternative mobility models. To the best of our knowledge, this study represents the first attempt to apply data-driven methodologies to route selection and estimation of arrival times of ambulances travelling with blue lights and sirens.
Published: 2019

3. Embedding co-production of nature-based solutions in urban governance: Emerging co-production capacities in three European cities

Author: Hölscher, Katharina, Frantzeskaki, Niki, Kindlon, Donnchadh, Collier, Marcus J., Dick, Gillian, Dziubała, Agnieszka, Lodder, Marleen, Osipiuk, Agnieszka, Quartier, Mien, Schepers, Selina, De Sijpe, Katrien Van, der Have, Carien van, Hölscher, Katharina, Frantzeskaki, Niki, Kindlon, Donnchadh, Collier, Marcus J., Dick, Gillian, Dziubała, Agnieszka, Lodder, Marleen, Osipiuk, Agnieszka, Quartier, Mien, Schepers, Selina, De Sijpe, Katrien Van, and der Have, Carien van
Abstract: This paper seeks to understand how co-production can become embedded as a collaborative governance practice by which city governments plan, deliver and steward nature-based solutions. To these ends, the paper analyses how policy officers manifest capacities for co-production in three European cities – Genk (Belgium), Glasgow (United Kingdom) and Poznań (Poland) – while experimenting with co-production to develop and scale nature-based solutions. Co-production capacities include conditions and activities to (1) create space for co-production, (2) safeguard inclusive and legitimate co-production, and (3) link co-production processes and results to contexts. The results demonstrate how policy officers in the three cities have mobilised and created resources, skills, institutional support and partnerships to implement diverse processes to co-produce nature-based solutions. While these conditions mark starting changes in urban governance, engaging with and embedding co-production causes tensions between the dynamic and diffuse nature of co-production and existing formal governance settings and processes. Lessons for strengthening the capacities to embed co-production as a collaborative governance practice in nature-based solutions planning, delivery and stewardship are: (1) embedding a tailor-made approach for inclusive co-production to meaningfully engage diverse actors in place-based settings, (2) embedding open-ended co-production with long-term benefits, and (3) embedding new relations and roles to sustain co-production.
Published: 2024

4. Targeted isolation of bacteria with potential to competitively exclude Staphylococcus aureus in the upper respiratory tract of pigs

Author: Vlasblom, Abel A., Patel, Shriram, Lawlor, Peadar G., Claesson, Marcus J., Crespo-Piazuelo, Daniel, Eckenberger, Julia, Huseyin, Chloe E., Elend, Christian, Wagenaar, Jaap A., Zomer, Aldert L., Duim, Birgitta, Vlasblom, Abel A., Patel, Shriram, Lawlor, Peadar G., Claesson, Marcus J., Crespo-Piazuelo, Daniel, Eckenberger, Julia, Huseyin, Chloe E., Elend, Christian, Wagenaar, Jaap A., Zomer, Aldert L., and Duim, Birgitta
Abstract: Considering global antimicrobial resistance (AMR) prevalence, alternative or complementary strategies to antimicrobial use, are of interest. Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is of particular interest as despite significant AMU reduction, LA-MRSA prevalence in pig husbandry has not decreased. We performed targeted isolation of bacterial species with potential antagonism against LA-MRSA in pig farms. Duplicate piglet nasal swabs from three European countries (Germany, Ireland and The Netherlands) were taken longitudinally from birth up to 10 weeks, one for amplicon sequencing and qPCR, and the other was cryopreserved for culturing. We identified potential probiotic species by anticorrelation analysis of bacterial abundance from amplicon sequencing data with quantitative S. aureus estimates from qPCR data from the samples. A literature-screen was performed on the species identified, to determine their probiotic potential. Following this, 1302 isolates were grown from selected cryopreserved swabs and identified using MALDI-TOF and additional 16S rRNA gene sequencing to isolate the anticorrelating species. Ninety-five isolates of interest were screened for absence of tetracycline resistance and hemolytic activity and whole genome sequencing was conducted to verify their taxonomy and to assess their AMR and virulence gene profile. Additional phenotypic antimicrobial resistance testing selected three different Lactococcus lactis strains. During an in vitro challenge using spent medium, all three strains demonstrated inhibition against two S. aureus strains. These L. lactis strains may have the ability to be used safely to reduce LA-MRSA carriage in the nasal passages of pigs but further in vivo testing is necessary to confirm this potential.Importance An approach to tackle antimicrobial resistance in livestock is to use competitive exclusion agents. We employed a sequencing guided isolation approach to identify bacterial species wi
Published: 2024

5. RF shimming in the cervical spinal cord at 7T

Author: Papp, Daniel, Gilbert, Kyle M., Cereza, Gaspard, D'Astous, Alexandre, Lopez-Rios, Nibardo, Boudreau, Mathieu, Couch, Marcus J., Yazdanbakhsh, Pedram, Barry, Robert L., Alonso Ortiz, Eva, Cohen-Adad, Julien, Papp, Daniel, Gilbert, Kyle M., Cereza, Gaspard, D'Astous, Alexandre, Lopez-Rios, Nibardo, Boudreau, Mathieu, Couch, Marcus J., Yazdanbakhsh, Pedram, Barry, Robert L., Alonso Ortiz, Eva, and Cohen-Adad, Julien
Abstract: Purpose : Advancing the development of 7 T MRI for spinal cord imaging is crucial for the enhanced diagnosis and monitoring of various neurodegenerative diseases and traumas. However, a significant challenge at this field strength is the transmit field inhomogeneity. Such inhomogeneity is particularly problematic for imaging the small, deep anatomical structures of the cervical spinal cord, as it can cause uneven signal intensity and elevate the local specific absorption ratio, compromising image quality. This multisite study explores several RF shimming techniques in the cervical spinal cord. Methods Data were collected from 5 participants between two 7 T sites with a custom 8Tx/20Rx parallel transmission coil. We explored two radiofrequency (RF) shimming approaches from an MRI vendor and four from an open-source toolbox, showcasing their ability to enhance transmit field and signal homogeneity along the cervical spinal cord. Results The circularly polarized (CP), coefficient of variation (CoV), and specific absorption rate (SAR) efficiency shim modes showed the highest B₁⁺ efficiency, and the vendor-based “patient” and “volume” modes showed the lowest B₁⁺ efficiency. The coefficient of variation method produced the highest CSF/spinal cord contrast on T₂*-weighted scans (ratio of 1.27 ± 0.03), and the lowest variation of that contrast along the superior–inferior axis. Conclusion The study's findings highlight the potential of RF shimming to advance 7 T MRI's clinical utility for central nervous system imaging by enabling more homogenous and efficient spinal cord imaging. Additionally, the research incorporates a reproducible Jupyter Notebook, enhancing the study's transparency and facilitating peer verification.
Published: 2024

6. Review on onshore and offshore large-scale seasonal hydrogen storage for electricity generation: Focusing on improving compression, storage, and roundtrip efficiency

Author: Adams, Marcus J, Wadge, Matthew D, Sheppard, Drew, Stuart, Alastair, Grant, David M, Adams, Marcus J, Wadge, Matthew D, Sheppard, Drew, Stuart, Alastair, and Grant, David M
Abstract: This article presents a comprehensive review of the current landscape and prospects of large-scale hydrogen storage technologies, with a focus on both onshore and offshore applications, and flexibility. Highlighting the evolving technological advancements, it explores storage and compression techniques, identifying potential research directions and avenues for innovation. Underwater hydrogen storage and hybrid metal hydride compressed gas tanks have been identified for offshore buffer storage, as well as exploration of using metal hydride slurries to transport hydrogen to/from offshore wind farms, coupled with low pressure, high flexibility electrolyser banks. Additionally, it explores the role of metal hydride hydrogen compressors and the integration of oxyfuel processes to enhance roundtrip efficiency. With insights into cost-effectiveness, environmental and technology considerations, and geographical factors, this review offers insights for policymakers, researchers, and industry stakeholders aiming to advance the deployment of large-scale hydrogen storage systems in the transition towards sustainable energy.
Published: 2024

7. Clinical algorithms for the monitoring and management of spontaneous, uncomplicated labour and childbirth

Author: MS Verloskunde, Cancer, Global Health, Child Health, Circulatory Health, Pasquale, Julia, Gialdini, Celina, Chamillard, Mónica, Diaz, Virginia, Rijken, Marcus J., Browne, Joyce L., Seto, Mimi Tin Yan, Cheung, Ka Wang, Bonet, Mercedes, WHO Intrapartum Care Algorithms Working Group, MS Verloskunde, Cancer, Global Health, Child Health, Circulatory Health, Pasquale, Julia, Gialdini, Celina, Chamillard, Mónica, Diaz, Virginia, Rijken, Marcus J., Browne, Joyce L., Seto, Mimi Tin Yan, Cheung, Ka Wang, Bonet, Mercedes, and WHO Intrapartum Care Algorithms Working Group
Published: 2024

8. Clinical practice and effect of carbon dioxide on outcomes in mechanically ventilated acute brain-injured patients: a secondary analysis of the ENIO study

Author: Robba, C, Battaglini, D, Abbas, A, Sarrió, E, Cinotti, R, Asehnoune, K, Taccone, F, Rocco, P, Schultz, M, Citerio, G, Stevens, R, Badenes, R, Abback, P, Codorniu, A, Sala, V, Astuto, M, Tringali, E, Alampi, D, Rocco, M, Maugeri, J, Bellissima, A, Filippini, M, Lazzeri, N, Cortegiani, A, Ippolito, M, Biston, P, Al-Gharyani, M, Chabanne, R, Astier, L, Soyer, B, Gaugain, S, Zimmerli, A, Pietsch, U, Filipovic, M, Brandi, G, Bicciato, G, Serrano, A, Monleon, B, van Vliet, P, Gerretsen, B, Ortiz-Macias, I, Oto, J, Enomoto, N, Matsuda, T, Masui, N, Garçon, P, Zarka, J, Vermeijden, W, Cornet, A, Gard, S, Domínguez, R, Bellini, M, Haedo, M, Lamot, L, Orquera, J, Biais, M, Georges, D, Baronial, A, Miranda-Ackerman, R, Barbosa-Camacho, F, Porter, J, Lopez-Morales, M, Geeraerts, T, Companion, B, Pérez-Torres, D, Prol-Silva, E, Yahya, H, Khaled, A, Ghulam, M, Andrea, C, Daniela, P, Deana, C, Vertigo, L, Chavez, M, Trujillo, R, Legros, V, Brochet, B, Huet, O, Geslain, M, van der Jagt, M, van Steenkiste, J, Ahmed, H, Coombs, A, Welbourne, J, Pineda, A, Castillo, V, Azab, M, Azzam, A, van Meenen, D, Gasca, G, Arellano, A, Galicia-Espinosa, F, García-Ramos, J, Yadav, G, Jha, A, Robert-Edan, V, Rodie-Talbere, P, Jain, G, Panda, S, Agarwal, S, Deewan, Y, Reza, S, Hossain, M, Papadas, C, Chantziara, V, Sklavou, C, Hourmant, Y, Grillot, N, Pirracchio, R, Akkari, A, Abdelaty, M, Hashim, A, Launey, Y, Masseret, E, Lasocki, S, Gergaud, S, Mouclier, N, Saxena, S, Agrawal, A, Mishra, S, Samal, S, Mijangos, J, Haënggi, M, Gurjar, M, Kaye, C, Godoy, D, Alvarez, P, Ioakeimidou, A, Ueno, Y, Elbuzidi, A, Piagnerelli, M, Elhadi, M, Digitale, J, Fong, N, Cerda, R, de la Torre Peredo, N, Mccredie, V, Suei, E, Haenggi, M, Samir, J, Robba, Chiara, Battaglini, Denise, Abbas, Abbas, Sarrió, Ezequiel, Cinotti, Raphael, Asehnoune, Karim, Taccone, Fabio S., Rocco, Patricia R., Schultz, Marcus J., Citerio, Giuseppe, Stevens, Robert David, Badenes, Rafael, Abback, Paër-Sélim, Codorniu, Anaïs, Sala, Vittoria Ludovica, Astuto, Marinella, Tringali, Eleonora, Alampi, Daniela, Rocco, Monica, Maugeri, Jessica Giuseppina, Bellissima, Agrippino, Filippini, Matteo, Lazzeri, Nicoletta, Cortegiani, Andrea, Ippolito, Mariachiara, Biston, Patrick, Al-Gharyani, Mohamed Fathi, Chabanne, Russell, Astier, Léo, Soyer, Benjamin, Gaugain, Samuel, Zimmerli, Alice, Pietsch, Urs, Filipovic, Miodrag, Brandi, Giovanna, Bicciato, Giulio, Serrano, Ainhoa, Monleon, Berta, van Vliet, Peter, Gerretsen, Benjamin Marcel, Ortiz-Macias, Iris Xochitl, Oto, Jun, Enomoto, Noriya, Matsuda, Tomomichi, Masui, Nobutaka, Garçon, Pierre, Zarka, Jonathan, Vermeijden, Wytze J., Cornet, Alexander Daniel, Gard, Sergio Reyes Infra, Domínguez, Rafael Cirino Lara, Bellini, Maria Mercedes, Haedo, Maria Milagros Gomez, Lamot, Laura, Orquera, Jose, Biais, Matthieu, Georges, Delphine, Baronial, Arvind, Miranda-Ackerman, Roberto Carlos, Barbosa-Camacho, Francisco José, Porter, John, Lopez-Morales, Miguel, Geeraerts, Thomas, Companion, Baptiste, Pérez-Torres, David, Prol-Silva, Estefanía, Yahya, Hana Basheer, Khaled, Ala, Ghulam, Mohamed, Andrea, Cracchiolo Neville, Daniela, Palma Maria, Deana, Cristian, Vertigo, Luigi, Chavez, Manuel J. Rivera, Trujillo, Rocio Mendoza, Legros, Vincent, Brochet, Benjamin, Huet, Olivier, Geslain, Marie, van der Jagt, Mathieu, van Steenkiste, Job, Ahmed, Hazem, Coombs, Alexander Edward, Welbourne, Jessie, Pineda, Ana Alicia Velarde, Castillo, Víctor Hugo Nubert, Azab, Mohammed A., Azzam, Ahmed Y., van Meenen, David Michael Paul, Gasca, Gilberto Adrian, Arellano, Alfredo, Galicia-Espinosa, Forttino, García-Ramos, José Carlos, Yadav, Ghanshyam, Jha, Amarendra Kumar, Robert-Edan, Vincent, Rodie-Talbere, Pierre-Andre, Jain, Gaurav, Panda, Sagarika, Agarwal, Sonika, Deewan, Yashbir, Reza, Syed Tariq, Hossain, Md. Mozaffer, Papadas, Christos, Chantziara, Vasiliki, Sklavou, Chrysanthi, Hourmant, Yannick, Grillot, Nicolas, Pirracchio, Romain, Akkari, Abdelraouf, Abdelaty, Mohamed, Hashim, Ahmed, Launey, Yoann, Masseret, Elodie, Lasocki, Sigismond, Gergaud, Soizic, Mouclier, Nicolas, Saxena, Sulekha, Agrawal, Avinash, Mishra, Shakti Bedanta, Samal, Samir, Mijangos, Julio Cesar, Haënggi, Mattias, Gurjar, Mohan, Kaye, Callum, Godoy, Daniela Agustin, Alvarez, Pablo, Ioakeimidou, Aikaterini, Ueno, Yoshitoyo, Elbuzidi, Abdurrahmaan Ali Suei, Piagnerelli, Michaël, Elhadi, Muhammed, Azab, Mohammed Atef, Digitale, Jean Catherine, Fong, Nicholas, Cerda, Ricardo Campos, de la Torre Peredo, Norma, McCredie, Victoria, Suei, Elbuzidi Abdurrahmaan Ali, Haenggi, Matthias, Samir, Jaber, Robba, C, Battaglini, D, Abbas, A, Sarrió, E, Cinotti, R, Asehnoune, K, Taccone, F, Rocco, P, Schultz, M, Citerio, G, Stevens, R, Badenes, R, Abback, P, Codorniu, A, Sala, V, Astuto, M, Tringali, E, Alampi, D, Rocco, M, Maugeri, J, Bellissima, A, Filippini, M, Lazzeri, N, Cortegiani, A, Ippolito, M, Biston, P, Al-Gharyani, M, Chabanne, R, Astier, L, Soyer, B, Gaugain, S, Zimmerli, A, Pietsch, U, Filipovic, M, Brandi, G, Bicciato, G, Serrano, A, Monleon, B, van Vliet, P, Gerretsen, B, Ortiz-Macias, I, Oto, J, Enomoto, N, Matsuda, T, Masui, N, Garçon, P, Zarka, J, Vermeijden, W, Cornet, A, Gard, S, Domínguez, R, Bellini, M, Haedo, M, Lamot, L, Orquera, J, Biais, M, Georges, D, Baronial, A, Miranda-Ackerman, R, Barbosa-Camacho, F, Porter, J, Lopez-Morales, M, Geeraerts, T, Companion, B, Pérez-Torres, D, Prol-Silva, E, Yahya, H, Khaled, A, Ghulam, M, Andrea, C, Daniela, P, Deana, C, Vertigo, L, Chavez, M, Trujillo, R, Legros, V, Brochet, B, Huet, O, Geslain, M, van der Jagt, M, van Steenkiste, J, Ahmed, H, Coombs, A, Welbourne, J, Pineda, A, Castillo, V, Azab, M, Azzam, A, van Meenen, D, Gasca, G, Arellano, A, Galicia-Espinosa, F, García-Ramos, J, Yadav, G, Jha, A, Robert-Edan, V, Rodie-Talbere, P, Jain, G, Panda, S, Agarwal, S, Deewan, Y, Reza, S, Hossain, M, Papadas, C, Chantziara, V, Sklavou, C, Hourmant, Y, Grillot, N, Pirracchio, R, Akkari, A, Abdelaty, M, Hashim, A, Launey, Y, Masseret, E, Lasocki, S, Gergaud, S, Mouclier, N, Saxena, S, Agrawal, A, Mishra, S, Samal, S, Mijangos, J, Haënggi, M, Gurjar, M, Kaye, C, Godoy, D, Alvarez, P, Ioakeimidou, A, Ueno, Y, Elbuzidi, A, Piagnerelli, M, Elhadi, M, Digitale, J, Fong, N, Cerda, R, de la Torre Peredo, N, Mccredie, V, Suei, E, Haenggi, M, Samir, J, Robba, Chiara, Battaglini, Denise, Abbas, Abbas, Sarrió, Ezequiel, Cinotti, Raphael, Asehnoune, Karim, Taccone, Fabio S., Rocco, Patricia R., Schultz, Marcus J., Citerio, Giuseppe, Stevens, Robert David, Badenes, Rafael, Abback, Paër-Sélim, Codorniu, Anaïs, Sala, Vittoria Ludovica, Astuto, Marinella, Tringali, Eleonora, Alampi, Daniela, Rocco, Monica, Maugeri, Jessica Giuseppina, Bellissima, Agrippino, Filippini, Matteo, Lazzeri, Nicoletta, Cortegiani, Andrea, Ippolito, Mariachiara, Biston, Patrick, Al-Gharyani, Mohamed Fathi, Chabanne, Russell, Astier, Léo, Soyer, Benjamin, Gaugain, Samuel, Zimmerli, Alice, Pietsch, Urs, Filipovic, Miodrag, Brandi, Giovanna, Bicciato, Giulio, Serrano, Ainhoa, Monleon, Berta, van Vliet, Peter, Gerretsen, Benjamin Marcel, Ortiz-Macias, Iris Xochitl, Oto, Jun, Enomoto, Noriya, Matsuda, Tomomichi, Masui, Nobutaka, Garçon, Pierre, Zarka, Jonathan, Vermeijden, Wytze J., Cornet, Alexander Daniel, Gard, Sergio Reyes Infra, Domínguez, Rafael Cirino Lara, Bellini, Maria Mercedes, Haedo, Maria Milagros Gomez, Lamot, Laura, Orquera, Jose, Biais, Matthieu, Georges, Delphine, Baronial, Arvind, Miranda-Ackerman, Roberto Carlos, Barbosa-Camacho, Francisco José, Porter, John, Lopez-Morales, Miguel, Geeraerts, Thomas, Companion, Baptiste, Pérez-Torres, David, Prol-Silva, Estefanía, Yahya, Hana Basheer, Khaled, Ala, Ghulam, Mohamed, Andrea, Cracchiolo Neville, Daniela, Palma Maria, Deana, Cristian, Vertigo, Luigi, Chavez, Manuel J. Rivera, Trujillo, Rocio Mendoza, Legros, Vincent, Brochet, Benjamin, Huet, Olivier, Geslain, Marie, van der Jagt, Mathieu, van Steenkiste, Job, Ahmed, Hazem, Coombs, Alexander Edward, Welbourne, Jessie, Pineda, Ana Alicia Velarde, Castillo, Víctor Hugo Nubert, Azab, Mohammed A., Azzam, Ahmed Y., van Meenen, David Michael Paul, Gasca, Gilberto Adrian, Arellano, Alfredo, Galicia-Espinosa, Forttino, García-Ramos, José Carlos, Yadav, Ghanshyam, Jha, Amarendra Kumar, Robert-Edan, Vincent, Rodie-Talbere, Pierre-Andre, Jain, Gaurav, Panda, Sagarika, Agarwal, Sonika, Deewan, Yashbir, Reza, Syed Tariq, Hossain, Md. Mozaffer, Papadas, Christos, Chantziara, Vasiliki, Sklavou, Chrysanthi, Hourmant, Yannick, Grillot, Nicolas, Pirracchio, Romain, Akkari, Abdelraouf, Abdelaty, Mohamed, Hashim, Ahmed, Launey, Yoann, Masseret, Elodie, Lasocki, Sigismond, Gergaud, Soizic, Mouclier, Nicolas, Saxena, Sulekha, Agrawal, Avinash, Mishra, Shakti Bedanta, Samal, Samir, Mijangos, Julio Cesar, Haënggi, Mattias, Gurjar, Mohan, Kaye, Callum, Godoy, Daniela Agustin, Alvarez, Pablo, Ioakeimidou, Aikaterini, Ueno, Yoshitoyo, Elbuzidi, Abdurrahmaan Ali Suei, Piagnerelli, Michaël, Elhadi, Muhammed, Azab, Mohammed Atef, Digitale, Jean Catherine, Fong, Nicholas, Cerda, Ricardo Campos, de la Torre Peredo, Norma, McCredie, Victoria, Suei, Elbuzidi Abdurrahmaan Ali, Haenggi, Matthias, and Samir, Jaber
Abstract: Purpose: The use of arterial partial pressure of carbon dioxide (PaCO2) as a target intervention to manage elevated intracranial pressure (ICP) and its effect on clinical outcomes remain unclear. We aimed to describe targets for PaCO2 in acute brain injured (ABI) patients and assess the occurrence of abnormal PaCO2 values during the first week in the intensive care unit (ICU). The secondary aim was to assess the association of PaCO2 with in-hospital mortality. Methods: We carried out a secondary analysis of a multicenter prospective observational study involving adult invasively ventilated patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH), or ischemic stroke (IS). PaCO2 was collected on day 1, 3, and 7 from ICU admission. Normocapnia was defined as PaCO2 > 35 and to 45 mmHg; mild hypocapnia as 32–35 mmHg; severe hypocapnia as 26–31 mmHg, forced hypocapnia as < 26 mmHg, and hypercapnia as > 45 mmHg. Results: 1476 patients (65.9% male, mean age 52 ± 18 years) were included. On ICU admission, 804 (54.5%) patients were normocapnic (incidence 1.37 episodes per person/day during ICU stay), and 125 (8.5%) and 334 (22.6%) were mild or severe hypocapnic (0.52 and 0.25 episodes/day). Forced hypocapnia and hypercapnia were used in 40 (2.7%) and 173 (11.7%) patients. PaCO2 had a U-shape relationship with in-hospital mortality with only severe hypocapnia and hypercapnia being associated with increased probability of in-hospital mortality (omnibus p value = 0.0009). Important differences were observed across different subgroups of ABI patients. Conclusions: Normocapnia and mild hypocapnia are common in ABI patients and do not affect patients' outcome. Extreme derangements of PaCO2 values were significantly associated with increased in-hospital mortality.
Published: 2024

9. Quantum Networking through Polarisation Entanglement Distribution

Author: Clark, Marcus J H and Clark, Marcus J H
Abstract: Quantum Technology is rapidly developing. To scale the technology beyond single monolithic systems, methods of interconnecting many systems are required. It is no longer a question of if interconnects will be used, but is now a question of when. The prevailing consensus is to interconnect quantum systems through the distribution of entanglement. This entanglement can then be used as a resource, and can be distributed through entanglement-based quantum networks (EQNets). Many different methods of constructing EQNets have been presented, however there is yet no consensus on whether any single design of system can fulfil the needs of all quantum technologies. In this work I present a type of fibre based EQNet, based on wavelength multiplexing of polarisation entangled photon pairs. A current realisable application of these EQNets is quantum key distribution (QKD). As such I use QKD as a performance metric of the quality and quantity of entanglement distribution (ED) in the polarisation-entanglement-based quantum networks (PEQNets) I constructed. I first demonstrate record uptime of a passively polarisation compensated fully-connected PEQNet, to date of publication. This achieved a continuous up-time of 10.8 days with metropolitan area optical fibre infrastructure (OFI) links, with 10 users. This allowed all parties to share entanglement throughout the demonstration with all other parties in the PEQNet, simultaneously in pairwise engagement links. To complete this work a quantum-enabled reconfigurable optical add-drop multiplexer (q-ROADM) was designed to dynamically assign all resources, such that the resourced can be dynamically reassigned. This is the first demonstration of an EQNet using a q-ROADM to distribute the entanglement resource. Interconnecting EQNets allows for ED between larger sets of users. Towards this goal of interconnectivity, a set of 2 PEQNets is demonstrated, where one is constructed with 16 users and the other with 3 users. Th
Published: 2024

10. The Plasma Lipidomic Landscape in Patients with Sepsis due to Community-acquired Pneumonia

Author: Sepsis and Inflammation, Epi Infectieziekten, Infection & Immunity, Epidemiology of Sepsis & Inflammation in Critically Ill Patients, JC onderzoeksprogramma Infectieziekten, Medische Staf Intensive Care, Chouchane, Osoul, Schuurman, Alex R, Reijnders, Tom D Y, Peters-Sengers, Hessel, Butler, Joe M, Uhel, Fabrice, Schultz, Marcus J, Bonten, Marc J, Cremer, Olaf L, Calfee, Carolyn S, Matthay, Michael A, Langley, Raymond J, Alipanah-Lechner, Narges, Kingsmore, Stephen F, Rogers, Angela, Weeghel, Michel van, Vaz, Frédéric M, van der Poll, Tom, Sepsis and Inflammation, Epi Infectieziekten, Infection & Immunity, Epidemiology of Sepsis & Inflammation in Critically Ill Patients, JC onderzoeksprogramma Infectieziekten, Medische Staf Intensive Care, Chouchane, Osoul, Schuurman, Alex R, Reijnders, Tom D Y, Peters-Sengers, Hessel, Butler, Joe M, Uhel, Fabrice, Schultz, Marcus J, Bonten, Marc J, Cremer, Olaf L, Calfee, Carolyn S, Matthay, Michael A, Langley, Raymond J, Alipanah-Lechner, Narges, Kingsmore, Stephen F, Rogers, Angela, Weeghel, Michel van, Vaz, Frédéric M, and van der Poll, Tom
Published: 2024

11. Climbing into their Skin to Understand Contextual Protein-Protein Associations and Localizations: Functional Investigations in Transgenic Live Model Organisms

Author: Long, Marcus J. C., Aye, Yimon, Long, Marcus J. C., and Aye, Yimon
Abstract: Borrowing some quotes from Harper Lee's novel "To Kill A Mockingbird" to help frame our manuscript, we discuss methods to profile local proteomes. We initially focus on chemical biology regimens that function in live organisms and use reactive biotin species for this purpose. We then consider ways to add new dimensions to these experimental regimens, principally by releasing less reactive (i. e., more selective) (preter)natural electrophiles. Although electrophile release methods may have lower resolution and label fewer proteins than biotinylation methods, their ability to probe simultaneously protein function and locale raises new and interesting possibilities for the field.|What Stirs Beneath. Understanding protein-specific interactomes, or localization, is crucial for decoding protein function. New biotinylation methods can do just that even in live organisms. However, these methods have some limitations as they are intrinsically unable to directly probe function. Here new methods that can investigate locale-specific reactivity, are discussed, opening routes to locale-specific perturbation of function. image
Published: 2024
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12. Embedding co-production of nature-based solutions in urban governance: Emerging co-production capacities in three European cities

Author: Social Urban Transitions, Planning Support Science, Hölscher, Katharina, Frantzeskaki, Niki, Kindlon, Donnchadh, Collier, Marcus J., Dick, Gillian, Dziubała, Agnieszka, Lodder, Marleen, Osipiuk, Agnieszka, Quartier, Mien, Schepers, Selina, De Sijpe, Katrien Van, der Have, Carien van, Social Urban Transitions, Planning Support Science, Hölscher, Katharina, Frantzeskaki, Niki, Kindlon, Donnchadh, Collier, Marcus J., Dick, Gillian, Dziubała, Agnieszka, Lodder, Marleen, Osipiuk, Agnieszka, Quartier, Mien, Schepers, Selina, De Sijpe, Katrien Van, and der Have, Carien van
Published: 2024

13. Personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS):study protocol for an international randomized clinical trial

Author: Sinnige, Jante S., Smit, Marry R., Ghose, Aniruddha, de Grooth, Harm-Jan, Itenov, Theis Skovsgaard, Ischaki, Eleni, Laffey, John, Paulus, Frederique, Póvoa, Pedro, Pierrakos, Charalampos, Pisani, Luigi, Roca, Oriol, Schultz, Marcus J., Szuldrzynski, Konstanty, Tuinman, Pieter R., Zimatore, Claudio, Bos, Lieuwe D. J., Sinnige, Jante S., Smit, Marry R., Ghose, Aniruddha, de Grooth, Harm-Jan, Itenov, Theis Skovsgaard, Ischaki, Eleni, Laffey, John, Paulus, Frederique, Póvoa, Pedro, Pierrakos, Charalampos, Pisani, Luigi, Roca, Oriol, Schultz, Marcus J., Szuldrzynski, Konstanty, Tuinman, Pieter R., Zimatore, Claudio, and Bos, Lieuwe D. J.
Abstract: BACKGROUND: Acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on "focal" or "non-focal" lung morphology has the potential to better target mechanical ventilation strategies of individual patients. However, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical. Lung ultrasound (LUS) is a non-invasive bedside tool that can accurately distinguish "focal" from "non-focal" lung morphology. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients leads to a reduction in 90-day mortality compared to conventional mechanical ventilation.METHODS: The Personalized Mechanical Ventilation Guided by UltraSound in Patients with Acute Respiratory Distress Syndrome (PEGASUS) study is an investigator-initiated, international, randomized clinical trial (RCT) that plans to enroll 538 invasively ventilated adult intensive care unit (ICU) patients with moderate to severe ARDS. Eligible patients will receive a LUS exam to classify lung morphology as "focal" or "non-focal". Thereafter, patients will be randomized within 12 h after ARDS diagnosis to receive standard care or personalized ventilation where the ventilation strategy is adjusted to the morphology subphenotype, i.e., higher positive end-expiratory pressure (PEEP) and recruitment maneuvers for "non-focal" ARDS and lower PEEP and prone positioning for "focal" ARDS. The primary endpoint is all-cause mortality at day 90. Secondary outcomes are mortality at day 28, ventilator-free days at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality, and number of complications (ventilator-associated pneumonia, pneumothorax, and need for rescue therapy). After a pilot phase of 80 patients, the correct interpretation of LUS images and correct application of the intervention within the safe limits
Published: 2024

14. Lineage tracing reveals transient phenotypic adaptation of tubular cells during acute kidney injury

Author: Buse, Marc, Cheng, Mingbo, Jankowski, Vera, Lellig, Michaela, Sterzer, Viktor, Strieder, Thiago, Leuchtle, Katja, Martin, Ina V., Seikrit, Claudia, Brinkkoettter, Paul, Crispatzu, Giuliano, Floege, Jürgen, Boor, Peter, Speer, Timotheus, Kramann, Rafael, Ostendorf, Tammo, Moeller, Marcus J., Costa, Ivan G., Stamellou, Eleni, Buse, Marc, Cheng, Mingbo, Jankowski, Vera, Lellig, Michaela, Sterzer, Viktor, Strieder, Thiago, Leuchtle, Katja, Martin, Ina V., Seikrit, Claudia, Brinkkoettter, Paul, Crispatzu, Giuliano, Floege, Jürgen, Boor, Peter, Speer, Timotheus, Kramann, Rafael, Ostendorf, Tammo, Moeller, Marcus J., Costa, Ivan G., and Stamellou, Eleni
Abstract: Tubular injury is the hallmark of acute kidney injury (AKI) with a tremendous impact on patients and health-care systems. During injury, any differentiated proximal tubular cell (PT) may transition into a specific injured phenotype, so-called “scattered tubular cell” (STC)-phenotype. To understand the fate of this specific phenotype, we generated transgenic mice allowing inducible, reversible, and irreversible tagging of these cells in a murine AKI model, the unilateral ischemia-reperfusion injury (IRI). For lineage tracing, we analyzed the kidneys using single-cell profiling during disease development at various time points. Labeled cells, which we defined by established endogenous markers, already appeared 8 h after injury and showed a distinct expression set of genes. We show that STCs re-differentiate back into fully differentiated PTs upon the resolution of the injury. In summary, we show the dynamics of the phenotypic transition of PTs during injury, revealing a reversible transcriptional program as an adaptive response during disease.
Published: 2024

15. Peri-operative night-time work of anaesthesiologists:A qualitative study of critical issues and proposals

Author: Ippolito, Mariachiara, Noto, Alberto, Lakbar, Ines, Chalkias, Athanasios, Afshari, Arash, Kranke, Peter, Garcia, Carolina Soledad Romero, Myatra, Sheila Nainan, Schultz, Marcus J., Giarratano, Antonino, Bilotta, Federico, De Robertis, Edoardo, Einav, Sharon, Cortegiani, Andrea, Ippolito, Mariachiara, Noto, Alberto, Lakbar, Ines, Chalkias, Athanasios, Afshari, Arash, Kranke, Peter, Garcia, Carolina Soledad Romero, Myatra, Sheila Nainan, Schultz, Marcus J., Giarratano, Antonino, Bilotta, Federico, De Robertis, Edoardo, Einav, Sharon, and Cortegiani, Andrea
Abstract: BACKGROUND Qualitative data on the opinions of anaesthesiologists regarding the impact of peri-operative night-time working conditions on patient safety are lacking. OBJECTIVE(S) This study aimed to achieve in-depth understanding of anaesthesiologists’ perceptions regarding the impact of night-time working conditions on peri-operative patient safety and actions that may be undertaken to mitigate perceived risks. DESIGN Qualitative analysis of responses to two open-ended questions. SETTING Online platform questionnaire promoted by the European Society of Anaesthesiology and Intensive Care (ESAIC). PARTICIPANTS The survey sample consisted of an international cohort of anaesthesiologists. MAIN OUTCOME MEASURES We identified and classified recurrent themes in the responses to questions addressing perceptions regarding (Q1) peri-operative night-time working conditions, which may affect patient safety and (Q2) potential solutions. RESULTS We analysed 2112 and 2113 responses to Q1 and Q2, respectively. The most frequently reported themes in relation to Q1 were a perceived reduction in professional performance accompanied by concerns regarding the possible consequences of work with fatigue (27%), and poor working conditions at night-time (35%). The most frequently proposed solutions in response to Q2 were a reduction of working hours and avoidance of 24-h shifts (21%), an increase in human resources (14%) and performance of only urgent or emergency surgeries at night (14%). CONCLUSION Overall, the surveyed anaesthesiologists believe that workload-to-staff imbalance and excessive working hours were potential bases for increased peri-operative risk for their patients, partly because of fatigue-related medical errors during night-time work. The performance of nonemergency elective surgical cases at night and lack of facilities were among the reported issues and potential targ, BACKGROUNDQualitative data on the opinions of anaesthesiologists regarding the impact of peri-operative night-time working conditions on patient safety are lacking.OBJECTIVE(S)This study aimed to achieve in-depth understanding of anaesthesiologists' perceptions regarding the impact of night-time working conditions on peri-operative patient safety and actions that may be undertaken to mitigate perceived risks.DESIGNQualitative analysis of responses to two open-ended questions.SETTINGOnline platform questionnaire promoted by the European Society of Anaesthesiology and Intensive Care (ESAIC).PARTICIPANTSThe survey sample consisted of an international cohort of anaesthesiologists.MAIN OUTCOME MEASURESWe identified and classified recurrent themes in the responses to questions addressing perceptions regarding (Q1) peri-operative night-time working conditions, which may affect patient safety and (Q2) potential solutions.RESULTSWe analysed 2112 and 2113 responses to Q1 and Q2, respectively. The most frequently reported themes in relation to Q1 were a perceived reduction in professional performance accompanied by concerns regarding the possible consequences of work with fatigue (27%), and poor working conditions at night-time (35%). The most frequently proposed solutions in response to Q2 were a reduction of working hours and avoidance of 24-h shifts (21%), an increase in human resources (14%) and performance of only urgent or emergency surgeries at night (14%).CONCLUSIONOverall, the surveyed anaesthesiologists believe that workload-to-staff imbalance and excessive working hours were potential bases for increased peri-operative risk for their patients, partly because of fatigue-related medical errors during night-time work. The performance of nonemergency elective surgical cases at night and lack of facilities were among the reported issues and potential targets for improvement measures. Further studies should investigate whether countermeasures can improve patient safety
Published: 2024

16. CYCLE: Learning to Self-Refine the Code Generation

Author: Ding, Yangruibo, Min, Marcus J., Kaiser, Gail, Ray, Baishakhi, Ding, Yangruibo, Min, Marcus J., Kaiser, Gail, and Ray, Baishakhi
Abstract: Pre-trained code language models have achieved promising performance in code generation and improved the programming efficiency of human developers. However, their self-refinement capability is typically overlooked by the existing evaluations of code LMs, which focus only on the accuracy of the one-time prediction. For the cases when code LMs fail to implement the correct program, developers actually find it hard to debug and fix the faulty prediction since it is not written by the developers themselves. Unfortunately, our study reveals that code LMs cannot efficiently self-refine their faulty generations as well. In this paper, we propose CYCLE framework, learning to self-refine the faulty generation according to the available feedback, such as the execution results reported by the test suites. We evaluate CYCLE on three popular code generation benchmarks, HumanEval, MBPP, and APPS. The results reveal that CYCLE successfully maintains, sometimes improves, the quality of one-time code generation, while significantly improving the self-refinement capability of code LMs. We implement four variants of CYCLE with varied numbers of parameters across 350M, 1B, 2B, and 3B, and the experiments show that CYCLE consistently boosts the code generation performance, by up to 63.5%, across benchmarks and varied model sizes. We also notice that CYCLE outperforms code LMs that have 3$\times$ more parameters in self-refinement., Comment: Camera-ready for OOPSLA'24
Published: 2024

17. Explicit stabilized multirate methods for the monodomain model in cardiac electrophysiology

Author: de Souza, Giacomo Rosilho, Grote, Marcus J., Pezzuto, Simone, Krause, Rolf, de Souza, Giacomo Rosilho, Grote, Marcus J., Pezzuto, Simone, and Krause, Rolf
Abstract: Fully explicit stabilized multirate (mRKC) methods are well-suited for the numerical solution of large multiscale systems of stiff ordinary differential equations thanks to their improved stability properties. To demonstrate their efficiency for the numerical solution of stiff, multiscale, nonlinear parabolic PDE's, we apply mRKC methods to the monodomain equation from cardiac electrophysiology. In doing so, we propose an improved version, specifically tailored to the monodomain model, which leads to the explicit exponential multirate stabilized (emRKC) method. Several numerical experiments are conducted to evaluate the efficiency of both mRKC and emRKC, while taking into account different finite element meshes (structured and unstructured) and realistic ionic models. The new emRKC method typically outperforms a standard implicit-explicit baseline method for cardiac electrophysiology. Code profiling and strong scalability results further demonstrate that emRKC is faster and inherently parallel without sacrificing accuracy.
Published: 2024

18. SemCoder: Training Code Language Models with Comprehensive Semantics

Author: Ding, Yangruibo, Peng, Jinjun, Min, Marcus J., Kaiser, Gail, Yang, Junfeng, Ray, Baishakhi, Ding, Yangruibo, Peng, Jinjun, Min, Marcus J., Kaiser, Gail, Yang, Junfeng, and Ray, Baishakhi
Abstract: Code Large Language Models (Code LLMs) have excelled at tasks like code completion but often miss deeper semantics such as execution effects and dynamic states. This paper aims to bridge the gap between Code LLMs' reliance on static text data and the need for thorough semantic understanding for complex tasks like debugging and program repair. We introduce a novel strategy to train Code LLMs with comprehensive semantics, encompassing high-level functional descriptions, local execution effects of individual statements, and overall input/output behavior, thereby linking static code text with dynamic execution states. We begin by collecting PyX, a clean code corpus of fully executable samples with functional descriptions and execution tracing. We propose training Code LLMs to write code and represent and reason about execution behaviors using natural language, mimicking human verbal debugging. This approach led to the development of SemCoder, a Code LLM with only 6.7B parameters, which shows competitive performance with GPT-3.5-turbo on code generation and execution reasoning tasks. SemCoder achieves 81.1% on HumanEval (GPT-3.5-turbo: 76.8%) and 54.5% on CRUXEval-I (GPT-3.5-turbo: 50.3%). We also study the effectiveness of SemCoder's monologue-style execution reasoning compared to concrete scratchpad reasoning, showing that our approach integrates semantics from multiple dimensions more smoothly. Finally, we demonstrate the potential of applying learned semantics to improve Code LLMs' debugging and self-refining capabilities.
Published: 2024

19. Two-dimensional cut plan optimization for cutter suction dredgers

Author: de Ruyter, Marcus J. M. and Anwar, Arif
Subjects: 627, TC Hydraulic engineering. Ocean engineering, VM Naval architecture. Shipbuilding. Marine engineering, TD Environmental technology. Sanitary engineering
Abstract: Optimal cut plans for cutter suction dredgers aim to maximize operational efficiency. Maximizing operational efficiency involves minimization of stoppage time resulting from non-productive dredger movements. To automate a systematic search for optimal twodimensional cut plans for cutter suction dredgers two models with an adaptive simulated annealing-based solution approach were developed. The first model, the dredge cut nesting model, optimizes irregular stock cutting problems where stencils represent dredge cuts and sheets represent dredging areas. Stencils are collections of unit dredge cuts with dimensions related to an effective cutting width which can be achieved with the cutter suction dredger considered. The objectives of the dredge cut nesting model are to maximize sheet coverage and to minimize stencil overlap. Centroids of unit dredge cuts of final nest layouts are extracted and used as grid nodes in the second model. The second model, the dredger routing model, optimizes asymmetric travelling salesperson problems with turning costs. The objectives of the dredger routing model are to minimize total route length and sum of turning angles, and to maximize average link length. A link consists of two or more route edges which are aligned with each other to within specified limits. A significant result of this research is that an engineering application of both models showed that two-dimensional cut plans for cutter suction dredgers can be systematically optimized and that dredger routes with minimum turning costs can be found. However, results also showed that the dredger routing model is not yet sophisticated enough to find cut plans for cutter suction dredgers for which overall project execution time is minimal.
Published: 2009

20. Novel techniques for the characterisation of exopolysaccharides secreted by lactic acid bacteria

Author: Chadha, Marcus J. and Laws, Andrew
Subjects: 600, Q Science (General), QD Chemistry
Abstract: This project investigated the structures and physical characteristics of exopolysaccharides (EPSs) secreted by lactic acid bacteria. The structure of a novel exopolysaccharide (EPS) produced by Lactobacillus acidophilus 5e2 has been characterised. Analysis of the anomeric region of the H-NMR showed that the repeating oligosaccharide contained seven monosaccharides. GC-MS showed the structure to consist of D-glucose, D-galactose and D-N-acetyl-glucosamine in a molar ratio of 3:3:1. The linkage analysis showed that there were two terminal, three di-linked and two tri-linked monosaccharides, and in collaboration with data generated from a series of D-NMR experiments, an overall structure was determined. The weight-average molecular weight (Mw) of the EPS secreted by Lactobacillus acidophilus 5e2 when grown in skimmed milk was monitored during extended fermentation times. During the exponential growth phase, the increase in Mw closely followed the increase in yield of EPS. Under the fermentation conditions applied in this study, few if any new polysaccharide chains were formed during this growth phase despite a twenty five-fold increase in the cell count; almost the entire increase in yield can be accounted for by an increase in chain length. These results suggested that synthesis of new EPS chains is switched off during the exponential and stationary phase of fermentation. The increase in yield observed in this period is a consequence of the bacteria's ability to extend existing chains right up to the mid-stationary phase. These results raise questions about the factors that control EPS production and chain length. Depolymerisation techniques have been shown to reduce the Mw of the polysaccharide in a controlled manner. The H-NMR results have shown that the physical methods, constant pressure and ultrasonic disruption break the EPS randomly through the repeating oligosaccharide unit; polydispersity data suggests that the breakages were occurring midchain. A change to the peaks in the anomeric region of the H-NMR spectrum showed that depolymerisation, by acid hydrolysis, was chemically modifying the EPS structure. The approximate intrinsic viscosities of the EPS produced by Lactobacillus acidophilus 5e2 were determined to range between 0.6–2.0 dL g-1 for the Mw range of 1.59x105 – 4.78x105 g mol-1. A capillary zone electrophoresis method was developed to determine the monosaccharide composition of two EPS samples. The method successfully determined D-glucose and Dgalactose, but a peak for D-N-acetyl-glucosamine was not seen. The method was sensitive compared to current techniques, but not as low as using a HP-AEC-PAD. A novel method using LC-MS was developed for the linkage analysis of EPSs. Methylation, hydrolysis and reductive amination were used to derivatise the polysaccharide, and the fragmentation patterns were examined to determine the different linkage positions. Due to undesirable further fragmentation the method could not unequivocally differentiate between the different linkage positions, but the method was capable of resolving the monosaccharides residues with different linkage positions, at approximately the correct relative ratio.
Published: 2009

21. The formulation of rinse-off productds with improved perfume deposition

Author: Goodall, Marcus J.
Subjects: 677
Published: 2005

22. Blind source separation : the effects of signal non-stationarity

Author: Alphey, Marcus J. T.
Subjects: 621.382
Abstract: This thesis investigates the effect of non-stationarity reduction, in the form of silence removal, on the performance of blind separation and deconvolution techniques for speech signals. An information-maximisation-based system is used for the separation of instantaneously mixed signals, and a decorrelating system for convolutively mixed signals. An introduction to the concepts of adaptive signal processing, blind signal processing and artificial neural networks is presented. A review of approaches to solving the blind signal separation and deconvolution problems is provided. The susceptibility of the information-maximisation approach to signal non-stationarity is discussed and two methods of silence identification and removal are compared and used to pre-process data before blind separation. The "infomax" approach is used to separate instantaneous mixtures, and is also modified to incorporate silence assessment and removal techniques to form an on-line system. Further modifications are made to the algorithm to investigate the effect of alternative update strategies, and these are compared with experimental results from identical modifications to diverse separating algorithms. A performance metric is used to assess the quality of separation achieved. The application of these techniques to convolutively mixed speech signals is also investigated, using the CoB1iSS algorithm. The effectiveness of the application of the silence removal techniques to both the time domain and frequency domain representations of the outputs is tested. While this form of non-stationarity reduction improves the rate of convergence for instantaneous mixtures, it does not cause any significant improvement in separation performance under most of the experimental conditions tested. No significant difference in performance was noted for the separation of convolutive mixtures in either the time or frequency domain.
Published: 2002

23. Contact patch dynamics of pneumatic tyres in pure sand

Author: Oliver, Marcus J.
Subjects: 629.2482
Published: 2002

24. Poly(a) selection introduces bias and undue noise in direct RNA-sequencing.

Author: Viscardi, Marcus J, Viscardi, Marcus J, Arribere, Joshua A, Viscardi, Marcus J, Viscardi, Marcus J, and Arribere, Joshua A
Abstract: BackgroundGenome-wide RNA-sequencing technologies are increasingly critical to a wide variety of diagnostic and research applications. RNA-seq users often first enrich for mRNA, with the most popular enrichment method being poly(A) selection. In many applications it is well-known that poly(A) selection biases the view of the transcriptome by selecting for longer tailed mRNA species.ResultsHere, we show that poly(A) selection biases Oxford Nanopore direct RNA sequencing. As expected, poly(A) selection skews sequenced mRNAs toward longer poly(A) tail lengths. Interestingly, we identify a population of mRNAs (> 10% of genes' mRNAs) that are inconsistently captured by poly(A) selection due to highly variable poly(A) tails, and demonstrate this phenomenon in our hands and in published data. Importantly, we show poly(A) selection is dispensable for Oxford Nanopore's direct RNA-seq technique, and demonstrate successful library construction without poly(A) selection, with decreased input, and without loss of quality.ConclusionsOur work expands the utility of direct RNA-seq by validating the use of total RNA as input, and demonstrates important technical artifacts from poly(A) selection that inconsistently skew mRNA expression and poly(A) tail length measurements.
Published: 2022

25. The structural basis of hyperpromiscuity in a core combinatorial network of type II toxin–antitoxin and related phage defense systems

Author: Ernits, Karin, Saha, Chayan Kumar, Brodiazhenko, Tetiana, Chouhan, Bhanu, Shenoy, Aditi, Buttress, Jessica A., Duque-Pedraza, Julián J., Bojar, Veda, Nakamoto, Jose A., Kurata, Tatsuaki, Egorov, Artyom A., Shyrokova, Lena, Johansson, Marcus J. O., Mets, Toomas, Rustamova, Aytan, Džigurski, Jelisaveta, Tenson, Tanel, Garcia-Pino, Abel, Strahl, Henrik, Elofsson, Arne, Hauryliuk, Vasili, Atkinson, Gemma C., Ernits, Karin, Saha, Chayan Kumar, Brodiazhenko, Tetiana, Chouhan, Bhanu, Shenoy, Aditi, Buttress, Jessica A., Duque-Pedraza, Julián J., Bojar, Veda, Nakamoto, Jose A., Kurata, Tatsuaki, Egorov, Artyom A., Shyrokova, Lena, Johansson, Marcus J. O., Mets, Toomas, Rustamova, Aytan, Džigurski, Jelisaveta, Tenson, Tanel, Garcia-Pino, Abel, Strahl, Henrik, Elofsson, Arne, Hauryliuk, Vasili, and Atkinson, Gemma C.
Abstract: Toxin-antitoxin (TA) systems are a large group of small genetic modules found in prokaryotes and their mobile genetic elements. Type II TAs are encoded as bicistronic (two-gene) operons that encode two proteins: a toxin and a neutralizing antitoxin. Using our tool NetFlax (standing for Network-FlaGs for toxins and antitoxins), we have performed a large-scale bioinformatic analysis of proteinaceous TAs, revealing interconnected clusters constituting a core network of TA-like gene pairs. To understand the structural basis of toxin neutralization by antitoxins, we have predicted the structures of 3,419 complexes with AlphaFold2. Together with mutagenesis and functional assays, our structural predictions provide insights into the neutralizing mechanism of the hyperpromiscuous Panacea antitoxin domain. In antitoxins composed of standalone Panacea, the domain mediates direct toxin neutralization, while in multidomain antitoxins the neutralization is mediated by other domains, such as PAD1, Phd-C, and ZFD. We hypothesize that Panacea acts as a sensor that regulates TA activation. We have experimentally validated 16 NetFlax TA systems and used domain annotations and metabolic labeling assays to predict their potential mechanisms of toxicity (such as membrane disruption, and inhibition of cell division or protein synthesis) as well as biological functions (such as antiphage defense). We have validated the antiphage activity of a RosmerTA system encoded by Gordonia phage Kita, and used fluorescence microscopy to confirm its predicted membrane-depolarizing activity. The interactive version of the NetFlax TA network that includes structural predictions can be accessed at http://netflax.webflags.se/.
Published: 2023
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26. Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake

Author: Ferrari, Alessandra, Ferrari, Alessandra, Whang, Emily, Xiao, Xu, Kennelly, John P, Romartinez-Alonso, Beatriz, Mack, Julia J, Weston, Thomas, Chen, Kai, Kim, Youngjae, Tol, Marcus J, Bideyan, Lara, Nguyen, Alexander, Gao, Yajing, Cui, Liujuan, Bedard, Alexander H, Sandhu, Jaspreet, Lee, Stephen D, Fairall, Louise, Williams, Kevin J, Song, Wenxin, Munguia, Priscilla, Russell, Robert A, Martin, Martin G, Jung, Michael E, Jiang, Haibo, Schwabe, John WR, Young, Stephen G, Tontonoz, Peter, Ferrari, Alessandra, Ferrari, Alessandra, Whang, Emily, Xiao, Xu, Kennelly, John P, Romartinez-Alonso, Beatriz, Mack, Julia J, Weston, Thomas, Chen, Kai, Kim, Youngjae, Tol, Marcus J, Bideyan, Lara, Nguyen, Alexander, Gao, Yajing, Cui, Liujuan, Bedard, Alexander H, Sandhu, Jaspreet, Lee, Stephen D, Fairall, Louise, Williams, Kevin J, Song, Wenxin, Munguia, Priscilla, Russell, Robert A, Martin, Martin G, Jung, Michael E, Jiang, Haibo, Schwabe, John WR, Young, Stephen G, and Tontonoz, Peter
Abstract: Intestinal absorption is an important contributor to systemic cholesterol homeostasis. Niemann-Pick C1 Like 1 (NPC1L1) assists in the initial step of dietary cholesterol uptake, but how cholesterol moves downstream of NPC1L1 is unknown. We show that Aster-B and Aster-C are critical for nonvesicular cholesterol movement in enterocytes. Loss of NPC1L1 diminishes accessible plasma membrane (PM) cholesterol and abolishes Aster recruitment to the intestinal brush border. Enterocytes lacking Asters accumulate PM cholesterol and show endoplasmic reticulum cholesterol depletion. Aster-deficient mice have impaired cholesterol absorption and are protected against diet-induced hypercholesterolemia. Finally, the Aster pathway can be targeted with a small-molecule inhibitor to manipulate cholesterol uptake. These findings identify the Aster pathway as a physiologically important and pharmacologically tractable node in dietary lipid absorption.
Published: 2023

27. Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Author: Tài, Pham, Leo, Heunk, Giacomo, Bellani, Fabiana, Madotto, Irene, Aragao, Gaëtan, Beduneau, Ewan C, Goligher, Giacomo, Grasselli, Jon Henrik, Laake, Jordi, Mancebo, Oscar, Peñuela, Lise, Piquilloud, Antonio, Pesenti, Hannah, Wunsch, Frank, van Haren, Laurent, Brochard, John G, Laffey, Abrough, Fekri, P Acharya, Subhash, Amin, Pravin, Arabi, Yaseen, Aragao, Irene, Bauer, Philippe, Beduneau, Gaëtan, Beitler, Jeremy, Berkius, Johan, Bugedo, Guillermo, Camporota, Luigi, Cerny, Vladimir, Cho, Young-Jae, Clarkson, Kevin, Estenssoro, Elisa, Goligher, Ewan, Grasselli, Giacomo, Gritsan, Alexey, Mohammadreza Hashemian, Seyed, Hermans, Greet, M Heunks, Leo, Jovanovic, Bojan, Kurahashi, Kiyoyasu, Henrik Laake, Jon, Matamis, Dimitrio, Moerer, Onnen, Molnar, Zsolt, Ozyilmaz, Ezgi, Panka, Bernardo, Papali, Alfred, Peñuelas, Óscar, Perbet, Sébastien, Piquilloud, Lise, Qiu, Haibo, Abdel Razek, Assem, Rittayamai, Nuttapol, Roldan, Rollin, Serpa Neto, Ary, Szuldrzynski, Konstanty, Talmor, Daniel, Tomescu, Dana, Van Haren, Frank, Villagomez, Asisclo, Ali Zeggwagh, Amine, Abe, Toshikazu, Aboshady, Abdelrhman, Acampo-de Jong, Melanie, Acharya, Subhash, Adderley, Jane, Adiguzel, Nalan, Kumar Agrawal, Vijay, Aguilar, Gerardo, Aguirre, Gaston, Aguirre-Bermeo, Hernan, Ahlström, Björn, Akbas, Türkay, Akker, Mustafa, Al Sadeh, Ghamdan, Alamri, Sultan, Algaba, Angela, Ali, Muneeb, Aliberti, Anna, Manuel Allegue, Jose, Alvarez, Diana, Amador, Joaquin, H Andersen, Finn, Ansari, Sharique, Apichatbutr, Yutthana, Apostolopoulou, Olympia, Arellano, Daniel, Arica, Mestanza, Arikan, Huseyin, Arinaga, Koichi, Arnal, Jean-Michel, Asano, Kengo, Asín-Corrochano, Marta, Milagrito Avalos Cabrera, Jesu, Avila Fuentes, Silvia, Aydemir, Semih, Aygencel, Gulbin, Azevedo, Luciano, Bacakoglu, Feza, Badie, Julio, Baedorf Kassis, Elia, Bai, Gabriela, Balaraj, Govindan, Ballico, Bruno, Banner-Goodspeed, Valerie, Banwarie, Preveen, Barbieri, Rosella, Baronia, Arvind, Barrett, Jonathan, Barrot, Loïc, Emilio Barrueco-Francioni, Jesu, Barry, Jeffrey, Bawangade, Harshal, Beavis, Sarah, Beck, Eduardo, Beehre, Nina, Belenguer Muncharaz, Alberto, Bellani, Giacomo, Belliato, Mirko, Bellissima, Agrippino, Beltramelli, Rodrigo, Ben Souissi, Asma, Benitez-Cano, Adela, Benlamin, Mohamed, Benslama, Abdellatif, Bento, Lui, Benvenuti, Daniela, Bernabe, Laura, Bersten, Andrew, Berta, Giacomo, Bertini, Pietro, Bertram-Ralph, Elliot, Besbes, Mohamed, Roberto Bettini, Lisandro, Beuret, Pascal, Bewley, Jeremy, Bezzi, Marco, Bhakhtiani, Lakshay, Bhandary, Rakesh, Bhowmick, Kaushik, Bihari, Shailesh, Bissett, Bernie, Blythe, David, Bocher, Simon, Boedjawan, Narain, M Bojanowski, Christine, Boni, Elisa, Boraso, Sabrina, Borelli, Massimo, Borello, Silvina, Borislavova, Margarita, J Bosma, Karen, Bottiroli, Maurizio, Boyd, Owen, Bozbay, Suha, Briva, Arturo, Brochard, Laurent, Bruel, Cédric, Bruni, Andrea, Buehner, Ulrike, Bulpa, Pierre, Burt, Karen, Buscot, Mathieu, Buttera, Stefania, Cabrera, Jorge, Caccese, Roberta, Caironi, Pietro, Canchos Gutierrez, Ivan, Canedo, Nancy, Cani, Alma, Cappellini, Iacopo, Carazo, Jesu, Pablo Cardonnet, Lui, Carpio, David, Carriedo, Demetrio, Carrillo, Ramón, Carvalho, João, Caser, Eliana, Castelli, Antonio, Castillo Quintero, Manuel, Castro, Heloisa, Catorze, Nuno, Cengiz, Melike, Cereijo, Enrique, Ceunen, Helga, Chaintoutis, Christo, Chang, Youjin, Chaparro, Gustavogcha, Chapman, Carmel, Chau, Simon, Eugenia Chavez, Cecilia, Chelazzi, Cosimo, Chelly, Jonathan, Chemouni, Frank, Chen, Kai, Chena, Ariel, Chiarandini, Paolo, Chilton, Phil, Chiumello, Davide, Chou-Lie, Yvette, Chudeau, Nicola, Cinel, Ismail, Cinnella, Gilda, Clark, Michele, Clark, Thoma, Clementi, Stefano, Coaguila, Lui, Jaspe Codecido, Alexi, Collins, Amy, Colombo, Riccardo, Conde, Juan, Consales, Guglielmo, Cook, Tim, Coppadoro, Andrea, Cornejo, Rodrigo, Cortegiani, Andrea, Coxo, Cristina, Neville Cracchiolo, Andrea, Crespo Ramirez, Mónica, Crova, Philippe, Cruz, José, Cubattoli, Lucia, Çukurova, Zafer, Curto, Francesco, Czempik, Piotr, D'Andrea, Rocco, da Silva Ramos, Fernando, Dangers, Laurence, Danguy des Déserts, Marc, Danin, Pierre-Eric, Dantas, Fabianne, Daubin, Cédric, Dawei, Wu, de Haro, Candelaria, de Jesus Montelongo, Felipe, De Mendoza, Diego, de Pablo, Raúl, De Pascale, Gennaro, De Rosa, Silvia, Decavèle, Maxen, Declercq, Pierre-Loui, Deicas, Alberto, Del Carmen Campos Moreno, María, Dellamonica, Jean, Delmas, Benjamin, Demirkiran, Oktay, Demirkiran, Hilmi, Dendane, Tarek, di Mussi, Rossella, Diakaki, Chrysi, Diaz, Anatilde, Diaz, Willy, Dikmen, Yalim, Dimoula, Aikaterini, Doble, Patricia, Doha, Nagwa, Domingos, Guilherme, Dres, Martin, Dries, David, Duggal, Abhijit, Duke, Graeme, Dunts, Pavel, Dybwik, Knut, Dykyy, Maksym, Eckert, Philippe, Efe, Serdar, Elatrous, Souheil, Elay, Gülseren, S Elmaryul, Abubaker, Elsaadany, Mohamed, Elsayed, Hany, Elsayed, Samar, Emery, Malo, Ena, Sébastien, Eng, Kevin, A Englert, Joshua, Erdogan, Elif, Ergin Ozcan, Perihan, Eroglu, Ege, Escobar, Miguel, Esen, Figen, Esen Tekeli, Arzu, Esquivel, Alejandro, Esquivel Gallegos, Helbert, Ezzouine, Hanane, Facchini, Alberto, Faheem, Mohammad, Fanelli, Vito, Fernanda Farina, Maria, Fartoukh, Muriel, Fehrle, Lutz, Feng, Feng, Feng, Yufeng, Fernandez, Irene, Fernandez, Borja, Lorena Fernandez-Rodriguez, Maria, Ferrando, Carlo, João Ferreira da Silva, Maria, Ferreruela, Mireia, Ferrier, Janet, Jesús Flamm Zamorano, Matia, Flood, Laura, Floris, Leda, Fluckiger, Martin, Forteza, Catalina, Fortunato, Antonella, Frans, Eric, Frattari, Antonella, Fredes, Sebastian, Frenzel, Tim, Fumagalli, Roberto, Andres Furche, Mariano, Fusari, Maurizio, Fysh, Edward, Luis Galeas-Lopez, Juan, Galerneau, Louis-Marie, Garcia, Analía, Fernanda Garcia, María, Garcia, Elisabet, Garcia Olivares, Pablo, Garlicki, Jaroslaw, Garnero, Aude, Garofalo, Eugenio, Gautam, Prabha, Gazenkampf, Andrey, Gelinotte, Stéphanie, Gelormini, Domenico, Ghrenassia, Etienne, Giacomucci, Angelo, Giannoni, Robert, Gigante, Andrea, Glober, Nancy, Gnesin, Paolo, Gollo, Yari, Gomaa, Dina, Gomero Paredes, Rosita, Gomes, Rui, Alejandro Gomez, Raúl, Gomez, Oscar, Gomez, Aroa, Gondim, Louise, Gonzalez, Manuel, Gonzalez, Isabel, Gonzalez-Castro, Alejandro, Gordillo Romero, Orlando, Gordo, Federico, Gouin, Philippe, Graf Santos, Jerónimo, Grainne, Rooney, Grando, Matilde, Granov Grabovica, Sanja, Grasso, Salvatore, Grasso, Rinaldo, Grimmer, Lisa, Grissom, Colin, Gu, Qing, Guan, Xiang-Dong, Guarracino, Fabio, Guasch, Neu, Guatteri, Luca, Gueret, Renaud, Guérin, Claude, Guerot, Emmanuel, Guitard, Pierre-Gilda, Gül, Fethi, Gumus, Ayca, Gurjar, Mohan, Gutierrez, Patricia, Hachimi, Abdelhamid, Hadzibegovic, Adi, Hagan, Samantha, Hammel, Clare, Han Song, Joo, Hanlon, Gabrielle, Heines, Serge, Henriksson, Johanna, Herbrecht, Jean-Etienne, Omar Heredia Orbegoso, Gabriel, Hermon, Andrew, Hernandez, Rosana, Hernandez, Carmen, Herrera, Lui, Herrera-Gutierrez, Manuel, Heunks, Leo, Hidalgo, Juan, Hill, Dianne, Holmquist, Dagmar, Homez, Marcela, Hongtao, Xia, Hormis, Anil, Horner, Daniel, Carmen Hornos, M, Hou, Meihong, House, Stacy, Housni, Brahim, Hugill, Keith, Humphreys, Sally, Humbert, Loui, Hunter, Stephanie, Hwa Young, Lee, Iezzi, Nicola, Ilutovich, Santiago, Inal, Volkan, Innes, Richard, Ioannides, Panagioti, Antonio Iotti, Giorgio, Ippolito, Mariachiara, Irie, Hiromasa, Iriyama, Hiroki, Itagaki, Taiga, Izura, Javier, Izza, Santiago, Jabeen, Rakhshanda, Jamaati, Hamidreza, Jamadarkhana, Sunil, Jamoussi, Amira, Jankowski, Milosz, Alberto Jaramillo, Lui, Jeon, Kyeongman, Jeong Lee, Seok, Jeswani, Deepak, Jha, Simant, Jiang, Liangyan, Jing, Chen, Jochmans, Sébastien, Anders Johnstad, Bror, Jongmin, Lee, Joret, Aurélie, Junhasavasdikul, Detajin, Teresa Jurado, Maria, Kam, Elisa, Kamohara, Hidenobu, Kane, Caroline, Kara, Iskender, Karakurt, Sait, Karnjanarachata, Cherdkiat, Kataoka, Jun, Katayama, Shinshu, Kaushik, Shuchi, Kelebek Girgin, Nermin, Kerr, Kathryn, Kerslake, Ian, Khairnar, Prakash, Khalid, Abidi, Khan, Akram, K Khanna, Ashish, Khorasanee, Reza, Kienhorst, Dieneke, Kirakli, Cenk, Knafelj, Rihard, Kol Kol, Mark, Kongpolprom, Napplika, Kopitko, Csaba, Korkmaz Ekren, Pervin, Kubisz-Pudelko, Agnieszka, Kulcsar, Zoltan, Kumasawa, Junji, Kuriyama, Akira, Kutchak, Fernanda, Labarca, Eduardo, Labat, Françoise, Laborda, César, Alberto Laca Barrera, Manuel, Lagache, Laurie, Landaverde Lopez, Antonio, Lanspa, Michael, Lascari, Valeria, Le Meur, Matthieu, Hwan Lee, Su, Ju Lee, Young, Lee, Jinwoo, Lee, Won-Yeon, Lee, Jarone, Legernaes, Terje, Leiner, Tamaa, Lemiale, Virginie, Leonor, Tiago, M Lepper, Philipp, Li, Dahuan, Li, Hongbin, Li, Oleg, Raquel Lima, Ana, Lind, Dan, Litton, Edward, Liu, Ning, Liu, Ling, Liu, Jialin, Llitjos, Jean-Françoi, Llorente, Beatriz, Lopez, Rodolfo, Elizabeth Lopez, Claudia, Lopez Nava, Claudia, Lovazzano, Pablo, Lu, Min, Lucchese, Francesca, Lugano, Manuela, Lugo Goytia, Gustavo, Luo, Hua, 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Gianmario, Mora Aznar, Maria, Morakul, Sunthiti, Morales, Maria, Moreno Torres, Daniel, Rolando Morocho Tutillo, Diego, Motherway, Catherine, Mouhssine, Doumiri, Mouloudi, Eleni, Muñoz, Tapia, Munoz de Cabo, Carlo, Mustafa, Mohamed, Muthuchellappan, Radhakrishnan, Muthukrishnan, Muraleekrishnan, Muttini, Stefano, Nagata, Isao, Nahar, Dick, Nakanishi, Misuzu, Nakayama, Izumi, Antonio Namendys-Silva, Silvio, Nanchal, Rahul, Nandakumar, Sivakumar, Nasi, Alessandra, Nasir, Kamal, Navalesi, Paolo, Naz Aslam, Tayyba, Nga Phan, Thuy, Nichol, Alistair, Niiyama, Shuhei, Nikolakopoulou, Sofia, Nikolic, Elena, Nitta, Kenichi, Noc, Marko, Nonas, Stephanie, Nseir, Saad, Nur Soyturk, Ayse, Obata, Yukako, Oeckler, Richard, Oguchi, Moe, Ohshimo, Shinichiro, Oikonomou, Marina, Ojados, Agueda, Teresa Oliveira, Maria, Oliveira Filho, Wilson, Oliveri, Carlo, Olmos, Aitor, Omura, Kazuya, Cristina Orlandi, Maria, Orsenigo, Francesca, Ortiz-Ruiz De Gordoa, Laura, Ota, Kei, Ovalle Olmos, Rainier, Öveges, 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Rodriguez, Gabriel, Rodriguez Gonzalez, Daniel, Yanina Rodriguez Tucto, Xandra, Rogers, Angela, Elena Romano, María, Rørtveit, Linda, Rose, Alastair, Roux, Damien, Rouze, Anahita, Nahuel Rubatto Birri, Paolo, Ruilan, Wang, Ruiz Robledo, Aldana, Luis Ruiz-Aguilar, Antonio, Sadahiro, Tomohito, Saez, Ignacio, Sagardia, Judith, Saha, Rajnish, Saha, Rohit, Saiphoklang, Narongkorn, Saito, Shigeki, Salem, Maie, Sales, Gabriele, Salgado, Patricia, Samavedam, Sriniva, Sami Mebazaa, Mhamed, Samuelsson, Line, San Juan Roman, Nandyelly, Sanchez, Patricia, Sanchez-Ballesteros, Jesu, Sandoval, Yazcitk, Sani, Emanuele, Santos, Martin, Santos, Carla, Sanui, Masamitsu, Saravanabavan, Lakshmikanthcharan, Sari, Sema, Sarkany, Agne, Sauneuf, Bertrand, Savioli, Monica, Sazak, Hilal, Scano, Riccardo, Schneider, Franci, Schortgen, Frédérique, J Schultz, Marcu, Leonie Schwarz, Gabriele, Seçkin Yücesoy, Faruk, Seely, Andrew, Seiler, Frederik, Seker Tekdos, Yasemin, Seok Chan, Kim, Serano, Luca, 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Mandy, Tamasato, Tamasato, Tang, Zhanhong, Tangsujaritvijit, Viratch, Taniguchi, Leandro, Taniguchi, Daisuke, Tarantino, Fabio, Teerapuncharoen, Krittika, Temprano, Susana, Terragni, Pierpaolo, Terzi, Nicola, Thakur, Anand, Theerawit, Pongdhep, W Thille, Arnaud, Thomas, Matt, Thungtitigul, Poungrat, Thyrault, Martial, Tilouch, Nejla, Timenetsky, Karina, Tirapu, Juna, Todeschini, Manuel, Tomas, Roser, Tomaszewski, Christian, Tonetti, Tommaso, Tonnelier, Alexandre, Trinder, John, Trongtrakul, Konlawij, Truwit, Jonathon, Tsuei, Betty, Tulaimat, Aiman, Turan, Sema, Turkoglu, Melda, Tyagi, Sanjeev, Ubeda, Alejandro, Vagginelli, Federica, Florencia Valenti, María, Vallverdu, Imma, Van Axel, Alisha, van den Hul, Ingrid, van der Hoeven, Han, Van Der Meer, Nardo, Vanhoof, Marc, Vargas-Ordoñez, Mónica, Vaschetto, Rosanna, Vascotto, Ettore, Vatsik, Maria, Vaz, Ana, Vazquez-Sanchez, Antonia, Ventura, Sara, Wytze Vermeijden, Jan, Vidal, Anxela, Vieira, Jocyelle, Vilela Costa Pinto, Bruno, 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Mariachiara Ippolito, Hiromasa Irie, Hiroki Iriyama, Taiga Itagaki, Javier Izura, Santiago Izza, Rakhshanda Jabeen, Hamidreza Jamaati, Sunil Jamadarkhana, Amira Jamoussi, Milosz Jankowski, Luis Alberto Jaramillo, Kyeongman Jeon, Seok Jeong Lee, Deepak Jeswani, Simant Jha, Liangyan Jiang, Chen Jing, Sébastien Jochmans, Bror Anders Johnstad, Lee Jongmin, Aurélie Joret, Detajin Junhasavasdikul, Maria Teresa Jurado, Elisa Kam, Hidenobu Kamohara, Caroline Kane, Iskender Kara, Sait Karakurt, Cherdkiat Karnjanarachata, Jun Kataoka, Shinshu Katayama, Shuchi Kaushik, Nermin Kelebek Girgin, Kathryn Kerr, Ian Kerslake, Prakash Khairnar, Abidi Khalid, Akram Khan, Ashish K Khanna, Reza Khorasanee, Dieneke Kienhorst, Cenk Kirakli, Rihard Knafelj, Mark Kol Kol, Napplika Kongpolprom, Csaba Kopitko, Pervin Korkmaz Ekren, Agnieszka Kubisz-Pudelko, Zoltan Kulcsar, Junji Kumasawa, Akira Kuriyama, Fernanda Kutchak, Eduardo Labarca, Françoise Labat, César Laborda, Manuel Alberto Laca Barrera, Laurie 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Maseda, Eleni Massa, Anna Mattsson, Jessica Maugeri, Victoria McCredie, James McCullough, Shay McGuinness, Andrew McKown, László Medve, Chengqing Mei, Ricard Mellado Artigas, Vitor Mendes, Mohamed Khalaf Ebraheim Mervat, Isabelle Michaux, Michael Mikhaeil, Olga Milagros, Igor Milet, Maria Teresa Millan, Zhang Minwei, Lucia Mirabella, Sanghamitra Mishra, Giovanni Mistraletti, Katsunori Mochizuki, Arif Moghal, Francesco Mojoli, Alexandre Molin, Raquel Montiel, Luca Montini (ORCID:0000-0003-4602-5134), Gianmario Monza, Maria Mora Aznar, Sunthiti Morakul, Maria Morales, Daniel Moreno Torres, Diego Rolando Morocho Tutillo, Catherine Motherway, Doumiri Mouhssine, Eleni Mouloudi, Tapia Muñoz, Carlos Munoz de Cabo, Mohamed Mustafa, Radhakrishnan Muthuchellappan, Muraleekrishnan Muthukrishnan, Stefano Muttini, Isao Nagata, Dick Nahar, Misuzu Nakanishi, Izumi Nakayama, Silvio Antonio Namendys-Silva, Rahul Nanchal, Sivakumar Nandakumar, Alessandra Nasi, Kamal Nasir, Paolo Navalesi, Tayyba Naz 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Joret, Aurélie, Junhasavasdikul, Detajin, Teresa Jurado, Maria, Kam, Elisa, Kamohara, Hidenobu, Kane, Caroline, Kara, Iskender, Karakurt, Sait, Karnjanarachata, Cherdkiat, Kataoka, Jun, Katayama, Shinshu, Kaushik, Shuchi, Kelebek Girgin, Nermin, Kerr, Kathryn, Kerslake, Ian, Khairnar, Prakash, Khalid, Abidi, Khan, Akram, K Khanna, Ashish, Khorasanee, Reza, Kienhorst, Dieneke, Kirakli, Cenk, Knafelj, Rihard, Kol Kol, Mark, Kongpolprom, Napplika, Kopitko, Csaba, Korkmaz Ekren, Pervin, Kubisz-Pudelko, Agnieszka, Kulcsar, Zoltan, Kumasawa, Junji, Kuriyama, Akira, Kutchak, Fernanda, Labarca, Eduardo, Labat, Françoise, Laborda, César, Alberto Laca Barrera, Manuel, Lagache, Laurie, Landaverde Lopez, Antonio, Lanspa, Michael, Lascari, Valeria, Le Meur, Matthieu, Hwan Lee, Su, Ju Lee, Young, Lee, Jinwoo, Lee, Won-Yeon, Lee, Jarone, Legernaes, Terje, Leiner, Tamaa, Lemiale, Virginie, Leonor, Tiago, M Lepper, Philipp, Li, Dahuan, Li, Hongbin, Li, Oleg, Raquel Lima, Ana, Lind, Dan, Litton, Edward, Liu, Ning, Liu, Ling, Liu, Jialin, Llitjos, Jean-Françoi, Llorente, Beatriz, Lopez, Rodolfo, Elizabeth Lopez, Claudia, Lopez Nava, Claudia, Lovazzano, Pablo, Lu, Min, Lucchese, Francesca, Lugano, Manuela, Lugo Goytia, Gustavo, Luo, Hua, Lynch, Ceri, Macheda, Sebastiano, Hugo Madrigal Robles, Victor, Maurizio Maggiore, Salvatore, Magret Iglesias, Mònica, Malaga, Peter, Mallapura Maheswarappa, Harish, Malpartida, Guillermo, Malyarchikov, Andrey, Mansson, Helena, Manzano, Anaid, Marey, Ismael, Marin, Nathalie, Del Carmen Marin, Maria, Markman, Eliana, Martin, Felix, Martin, Alex, Martin Dal Gesso, Cristina, Martinez, Felipe, Martínez-Fidalgo, Conchita, Martin-Loeches, Ignacio, Mas, Arantxa, Masaaki, Sakuraya, Maseda, Emilio, Massa, Eleni, Mattsson, Anna, Maugeri, Jessica, Mccredie, Victoria, Mccullough, Jame, Mcguinness, Shay, Mckown, Andrew, Medve, László, Mei, Chengqing, Mellado Artigas, Ricard, Mendes, Vitor, Khalaf Ebraheim Mervat, Mohamed, Michaux, Isabelle, Mikhaeil, 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Manzano, Ismael Marey, Nathalie Marin, Maria Del Carmen Marin, Eliana Markman, Felix Martin, Alex Martin, Cristina Martin Dal Gesso, Felipe Martinez, Conchita Martínez-Fidalgo, Ignacio Martin-Loeches, Arantxa Mas, Sakuraya Masaaki, Emilio Maseda, Eleni Massa, Anna Mattsson, Jessica Maugeri, Victoria McCredie, James McCullough, Shay McGuinness, Andrew McKown, László Medve, Chengqing Mei, Ricard Mellado Artigas, Vitor Mendes, Mohamed Khalaf Ebraheim Mervat, Isabelle Michaux, Michael Mikhaeil, Olga Milagros, Igor Milet, Maria Teresa Millan, Zhang Minwei, Lucia Mirabella, Sanghamitra Mishra, Giovanni Mistraletti, Katsunori Mochizuki, Arif Moghal, Francesco Mojoli, Alexandre Molin, Raquel Montiel, Luca Montini (ORCID:0000-0003-4602-5134), Gianmario Monza, Maria Mora Aznar, Sunthiti Morakul, Maria Morales, Daniel Moreno Torres, Diego Rolando Morocho Tutillo, Catherine Motherway, Doumiri Mouhssine, Eleni Mouloudi, Tapia Muñoz, Carlos Munoz de Cabo, Mohamed Mustafa, Radhakrishnan Muthuchellappan, Muraleekrishnan Muthukrishnan, Stefano Muttini, Isao Nagata, Dick Nahar, Misuzu Nakanishi, Izumi Nakayama, Silvio Antonio Namendys-Silva, Rahul Nanchal, Sivakumar Nandakumar, Alessandra Nasi, Kamal Nasir, Paolo Navalesi, Tayyba Naz Aslam, Thuy Nga Phan, Alistair Nichol, Shuhei Niiyama, Sofia Nikolakopoulou, Elena Nikolic, Kenichi Nitta, Marko Noc, Stephanie Nonas, Saad Nseir, Ayse Nur Soyturk, Yukako Obata, Richard Oeckler, Moe Oguchi, Shinichiro Ohshimo, Marina Oikonomou, Agueda Ojados, Maria Teresa Oliveira, Wilson Oliveira Filho, Carlo Oliveri, Aitor Olmos, Kazuya Omura, Maria Cristina Orlandi, Francesca Orsenigo, Laura Ortiz-Ruiz De Gordoa, Kei Ota, Rainier Ovalle Olmos, Nándo Öveges, Peter Oziemski, Ozlem Ozkan Kuscu, Ezgi Özyilmaz, Fernando Pachas Alvarado, Gonzalo Pagella, Vijayanand Palaniswamy, Eugenio Luis Palazon Sanchez, Salvatore Palmese, Guojun Pan, Wensen Pan, Metaxia Papanikolaou, Theonymfi Papavasilopoulou, Ameet Parekh, Rachael Parke, Francisco J Parrilla, Dácil Parrilla, Taha Pasha, Laura Pasin, Luis Patão, Mayur Patel, Grisma Patel, Basanta Kumar Pati, Jayaprakash Patil, Saroj Pattnaik, Daniel Paul, Maurizio Pavesi, Vanesa Alejandra Pavlotsky, Graciela Paz, Enrique Paz, Elisabetta Pecci, Carlos Pellegrini, Andrea Gabriela Peña Padilla, Gaetano Perchiazzi, Tiago Pereira, Vera Pereira, Manuel Perez, Cesar Perez Calvo, Meisy Perez Cheng, Ronald Perez Maita, Rodrigo Pérez-Araos, Purificación Perez-Teran, David Perez-Torres, Gavin Perkins, Paolo Persona, Tananchai Petnak, Marina Petrova, Tai Pham, François Philippart, Edoardo Picetti, Elisabetta Pierucci, Edoardo Piervincenzi, Riccardo Pinciroli, Maria-Consuelo Pintado, Thomas Piraino, Stephanie Piras, Claudio Piras, Pattarin Pirompanich, Luigi Pisani, Enrique Platas, Gustavo Plotnikow, Willy Porras, Virginia Porta, Mariana Portilla, José Portugal, Pedro Povoa, Gwenael Prat, Romina Pratto, Gabriel Preda, Isidro Prieto, Estefania Prol-Silva, Richard Pugh, Yupeng Qi, Chuanyun Qian, Tiehe Qin, Hongping Qu, Teobaldo Quintana, Rosari Quispe Sierra, Rocio Quispe Soto, Raihan Rabbani, Mohamed Rabee, Ahmed Rabie, Maria Augusta Rahe Pereira, Ashish Rai, Sundar Raj Ashok, Mostafa Rajab, Navin Ramdhani, Elizabeth Ramey, Marco Ranieri, Darshana Rathod, Banambar Ray, Shihan Mahmud Redwanul Huq, Adrian Regli, Rosa Reina, Natalia Resano Sarmiento, Faustine Reynaud, Gemma Rialp, Pilar Ricart, Todd Rice, Angus Richardson, Marcelo Rieder, Martin Rinket, Fernando Rios, Alejandro Risso Vazquez, Ivano Riva, Monaly Rivette, Oriol Roca, Ferran Roche-Campo, Covadonga Rodriguez, Gabriel Rodriguez, Daniel Rodriguez Gonzalez, Xandra Yanina Rodriguez Tucto, Angela Rogers, María Elena Romano, Linda Rørtveit, Alastair Rose, Damien Roux, Anahita Rouze, Paolo Nahuel Rubatto Birri, Wang Ruilan, Aldana Ruiz Robledo, Antonio Luis Ruiz-Aguilar, Tomohito Sadahiro, Ignacio Saez, Judith Sagardia, Rajnish Saha, Rohit Saha, Narongkorn Saiphoklang, Shigeki Saito, Maie Salem, Gabriele Sales, Patricia Salgado, Srinivas Samavedam, Mhamed Sami Mebazaa, Line Samuelsson, Nandyelly San Juan Roman, Patricia Sanchez, Jesus Sanchez-Ballesteros, Yazcitk Sandoval, Emanuele Sani, Martin Santos, Carla Santos, Masamitsu Sanui, Lakshmikanthcharan Saravanabavan, Sema Sari, Agnes Sarkany, Bertrand Sauneuf, Monica Savioli, Hilal Sazak, Riccardo Scano, Francis Schneider, Frédérique Schortgen, Marcus J Schultz, Gabriele Leonie Schwarz, Faruk Seçkin Yücesoy, Andrew Seely, Frederik Seiler, Yasemin Seker Tekdos, Kim Seok Chan, Luca Serano, Wojciech Serednicki, Mariano Setten, Asim Shah, Bhagyesh Shah, You Shang, Pradeep Shanmugasundaram, Konstantin Shapovalov, Eman Shebl, Takuya Shiga, Nobuaki Shime, Phil Shin, Jack Short, Chen Shuhua, Sughrat Siddiqui, Juan Ignacio Silesky Jimenez, Daniel Silva, Betania Silva Sales, Koen Simons, Brit Ågot Sjøbø, David Slessor, Jakub Smiechowicz, Nathan Smischney, Paul Smith, Tim Smith, Mark Smith, Sarah Snape, Lindi Snyman, Filiep Soetens, Kyung Sook Hong, Miguel Ángel Sosa Medellin, Giovanna Soto, Xavier Souloy, Elsa Sousa, Stefania Sovatzis, Didem Sozutek, Savino Spadaro, Marco Spagnoli, Martin Spångfors, Nick Spittle, Mike Spivey, Andrew Stapleton, Branislava Stefanovic, Lorraine Stephenson, Elizabeth Stevenson, Kristian Strand, Maria Teresa Strano, Slavenka Straus, Chenliang Sun, Rongqing Sun, Venkat Sundaram, Tai SunPark, Elisabeth Surlemont, Yuda Sutherasan, Zsuzsanna Szabo, Christopher Tainter, Akihiro Takaba, Mandy Tallott, Tamasato Tamasato, Zhanhong Tang, Viratch Tangsujaritvijit, Leandro Taniguchi, Daisuke Taniguchi, Fabio Tarantino, Krittika Teerapuncharoen, Susana Temprano, Pierpaolo Terragni, Nicolas Terzi, Anand Thakur, Pongdhep Theerawit, Arnaud W Thille, Matt Thomas, Poungrat Thungtitigul, Martial Thyrault, Nejla Tilouch, Karina Timenetsky, Juna Tirapu, Manuel Todeschini, Roser Tomas, Christian Tomaszewski, Tommaso Tonetti, Alexandre Tonnelier, John Trinder, Konlawij Trongtrakul, Jonathon Truwit, Betty Tsuei, Aiman Tulaimat, Sema Turan, Melda Turkoglu, Sanjeev Tyagi, Alejandro Ubeda, Federica Vagginelli, María Florencia Valenti, Imma Vallverdu, Alisha Van Axel, Ingrid van den Hul, Hans van der Hoeven, Nardo Van Der Meer, Marc Vanhoof, Mónica Vargas-Ordoñez, Rosanna Vaschetto, Ettore Vascotto, Maria Vatsik, Ana Vaz, Antonia Vazquez-Sanchez, Sara Ventura, Jan Wytze Vermeijden, Anxela Vidal, Jocyelle Vieira, Bruno Vilela Costa Pinto, Ana Villagra, Cristina Villegas Succar, Ole Georg Vinorum, Giovanni Vitale, Ramesh Vj, Ana Vochin, Guillaume Voiriot, Carlo Alberto Volta, Magnus von Seth, Maazouzi Wajdi, Don Walsh, Shouhong Wang, Gabriel Wardi, Nils Christian Ween-Velken, Bi-Lin Wei, Dolf Weller, Deborah Welsh, Ingeborg Welters, Michael Wert, Simon Whiteley, Elizabeth Wilby, Erin Williams, Karen Williams, Antoinette Wilson, Jadwiga Wojtas, Jin Won Huh, David Wrathall, Christopher Wright, Jian-Feng Wu, Guo Xi, Zheng-Jiang Xing, Hongyang Xu, Kotaro Yamamoto, Jie Yan, Julio Yáñez, Xiaobo Yang, Elliot Yates, Ozlem Yazicioglu Mocin, Zhenglong Ye, Fatma Yildirim, Norifumi Yoshida, Hector Higo Leon Yoshido, Bo Young Lee, Rongguo Yu, Gong Yu, Tao Yu, Boyun Yuan, Nadwipa Yuangtrakul, Tetsuya Yumoto, Xie Yun, Graciela Zakalik, Ahmad Zaki, Begoña Zalba-Etayo, Massimo Zambon, Bin Zang, Gianluca Zani, Jonathan Zarka, Simone Maria Zerbi, Avsar Zerman, Harald Zetterquist, Jiuzhi Zhang, Hongwen Zhang, Wei Zhang, Guoxiu Zhang, Weixin Zhang, Hongsheng Zhao, Jia Zheng, Bin Zhu, and Ronald Zumaran
Abstract: Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0-4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 d
Published: 2023

28. Genetic insights into resting heart rate and its role in cardiovascular disease

Author: van de Vegte, Yordi, Eppinga, Ruben P., van der Ende, M. Yldau, Hagemeijer, Yanick, Mahendran, Yuvaraj V., Salfati, Elias Y., Smith, Albert E., Tan, Vanessa, Arking, Dan V., Ntalla, Ioanna, Appel, Emil A., Schurmann, Claudia, Brody, Jennifer, Rueedi, Rico, Polasek, Ozren, Sveinbjornsson, Gardar, Lecoeur, Cecile, Ladenvall, Claes, Zhao, Jing Hua, Isaacs, Aaron, Wang, Lihua, Luan, Jian'an, Hwang, Shih-Jen, Mononen, Nina U., Auro, Kirsi F., Jackson, Anne, Bielak, Lawrence, Zeng, Linyao, Shah, Nabi, Nethander, Maria, Campbell, Archie, Rankinen, Tuomo, Pechlivanis, Sonali, Qi, Lu, Zhao, Wei, Rizzi, Federica, Tanaka, Toshiko, Robino, Antonietta, Cocca, Massimiliano, Lange, Leslie, Mueller-Nurasyid, Martina, Roselli, Carolina E., Zhang, Weihua, Kleber, Marcus J., Guo, Xiuqing, Lin, Henry E., Pavani, Francesca, Galesloot, Tessel, Noordam, Raymond E., Milaneschi, Yuri, Schraut, Katharina, den Hoed, Marcel, Degenhardt, Frauke E., Trompet, Stella, van den Berg, Marten, Pistis, Giorgio, Tham, Yih-Chung S., Weiss, Stefan L., Sim, Xueling J., Li, Hengtong M., van der Most, Peter, Nolte, Ilja, Lyytikaeinen, Leo-Pekka R., Said, M. Abdullah, Witte, Daniel, Iribarren, Carlos M., Launer, Lenore S., Ring, Susan, de Vries, Paul, Sever, Peter P., Linneberg, Allan, Bottinger, Erwin M., Padmanabhan, Sandosh, Psaty, Bruce, Sotoodehnia, Nona, Kolcic, Ivana, Roshandel, Delnaz D., Paterson, Andrew O., Arnar, David F., Gudbjartsson, Daniel, Holm, Hilma, Balkau, Beverley T., Silva, Claudia H., Newton-Cheh, Christopher, Nikus, Kjell, Salo, Perttu L., Mohlke, Karen A., Peyser, Patricia, Schunkert, Heribert, Lorentzon, Mattias, Lahti, Jari C., Rao, Dabeeru C., Cornelis, Marilyn D., Faul, Jessica A., Smith, Jennifer, Stolarz-Skrzypek, Katarzyna, Bandinelli, Stefania, Concas, Maria Pina, Sinagra, Gianfranco, Meitinger, Thomas, Waldenberger, Melanie F., Sinner, Moritz, Strauch, Konstantin E., Delgado, Graciela D., Taylor, Kent, Yao, Jie, Foco, Luisa, Melander, Olle, de Graaf, Jacqueline, de Mutsert, Renee, de Geus, Eco J. C., Johansson, Åsa, Joshi, Peter K., Lind, Lars, Franke, Andre W., Macfarlane, Peter V., Tarasov, Kirill, Tan, Nicholas B., Felix, Stephan, Tai, E-Shyong Q., Quek, Debra, Snieder, Harold, Ormel, Johan, Ingelsson, Martin, Lindgren, Cecilia P., Morris, Andrew T., Raitakari, Olli, Hansen, Torben, Assimes, Themistocles, Gudnason, Vilmundur J., Timpson, Nicholas C., Morrison, Alanna B., Munroe, Patricia P., Strachan, David, Grarup, Niels, Loos, Ruth J. F. R., Heckbert, Susan, Vollenweider, Peter, Hayward, Caroline, Stefansson, Kari, Froguel, Philippe, Groop, Leif J., Wareham, Nicholas M., van Duijn, Cornelia F., Feitosa, Mary J., O'Donnell, Christopher, Kaehoenen, Mika, Perola, Markus, Boehnke, Michael, Kardia, Sharon L. R., Erdmann, Jeanette, Palmer, Colin N. A., Ohlsson, Claes J., Porteous, David G., Eriksson, Johan, Bouchard, Claude, Moebus, Susanne, Kraft, Peter R., Weir, David, Cusi, Daniele, Ferrucci, Luigi, Ulivi, Sheila, Girotto, Giorgia, Correa, Adolfo, Kaeaeb, Stefan, Peters, Annette C., Chambers, John S., Kooner, Jaspal, Maerz, Winfried I., Rotter, Jerome A., Hicks, Andrew, Smith, J. Gustav, Kiemeney, Lambertus A. L. M. O., Mook-Kanamori, Dennis, Penninx, Brenda W. J. H., Gyllensten, Ulf, Wilson, James, Burgess, Stephen, Sundström, Johan, Lieb, Wolfgang, Jukema, J. Wouter, Eijgelsheim, Mark, Lakatta, Edward L. M., Cheng, Ching-Yu, Doerr, Marcus, Wong, Tien-Yin, Sabanayagam, Charumathi J., Oldehinkel, Albertine, Riese, Harriette, Lehtimaeki, Terho, Verweij, Niek, van der Harst, Pim, van de Vegte, Yordi, Eppinga, Ruben P., van der Ende, M. Yldau, Hagemeijer, Yanick, Mahendran, Yuvaraj V., Salfati, Elias Y., Smith, Albert E., Tan, Vanessa, Arking, Dan V., Ntalla, Ioanna, Appel, Emil A., Schurmann, Claudia, Brody, Jennifer, Rueedi, Rico, Polasek, Ozren, Sveinbjornsson, Gardar, Lecoeur, Cecile, Ladenvall, Claes, Zhao, Jing Hua, Isaacs, Aaron, Wang, Lihua, Luan, Jian'an, Hwang, Shih-Jen, Mononen, Nina U., Auro, Kirsi F., Jackson, Anne, Bielak, Lawrence, Zeng, Linyao, Shah, Nabi, Nethander, Maria, Campbell, Archie, Rankinen, Tuomo, Pechlivanis, Sonali, Qi, Lu, Zhao, Wei, Rizzi, Federica, Tanaka, Toshiko, Robino, Antonietta, Cocca, Massimiliano, Lange, Leslie, Mueller-Nurasyid, Martina, Roselli, Carolina E., Zhang, Weihua, Kleber, Marcus J., Guo, Xiuqing, Lin, Henry E., Pavani, Francesca, Galesloot, Tessel, Noordam, Raymond E., Milaneschi, Yuri, Schraut, Katharina, den Hoed, Marcel, Degenhardt, Frauke E., Trompet, Stella, van den Berg, Marten, Pistis, Giorgio, Tham, Yih-Chung S., Weiss, Stefan L., Sim, Xueling J., Li, Hengtong M., van der Most, Peter, Nolte, Ilja, Lyytikaeinen, Leo-Pekka R., Said, M. Abdullah, Witte, Daniel, Iribarren, Carlos M., Launer, Lenore S., Ring, Susan, de Vries, Paul, Sever, Peter P., Linneberg, Allan, Bottinger, Erwin M., Padmanabhan, Sandosh, Psaty, Bruce, Sotoodehnia, Nona, Kolcic, Ivana, Roshandel, Delnaz D., Paterson, Andrew O., Arnar, David F., Gudbjartsson, Daniel, Holm, Hilma, Balkau, Beverley T., Silva, Claudia H., Newton-Cheh, Christopher, Nikus, Kjell, Salo, Perttu L., Mohlke, Karen A., Peyser, Patricia, Schunkert, Heribert, Lorentzon, Mattias, Lahti, Jari C., Rao, Dabeeru C., Cornelis, Marilyn D., Faul, Jessica A., Smith, Jennifer, Stolarz-Skrzypek, Katarzyna, Bandinelli, Stefania, Concas, Maria Pina, Sinagra, Gianfranco, Meitinger, Thomas, Waldenberger, Melanie F., Sinner, Moritz, Strauch, Konstantin E., Delgado, Graciela D., Taylor, Kent, Yao, Jie, Foco, Luisa, Melander, Olle, de Graaf, Jacqueline, de Mutsert, Renee, de Geus, Eco J. C., Johansson, Åsa, Joshi, Peter K., Lind, Lars, Franke, Andre W., Macfarlane, Peter V., Tarasov, Kirill, Tan, Nicholas B., Felix, Stephan, Tai, E-Shyong Q., Quek, Debra, Snieder, Harold, Ormel, Johan, Ingelsson, Martin, Lindgren, Cecilia P., Morris, Andrew T., Raitakari, Olli, Hansen, Torben, Assimes, Themistocles, Gudnason, Vilmundur J., Timpson, Nicholas C., Morrison, Alanna B., Munroe, Patricia P., Strachan, David, Grarup, Niels, Loos, Ruth J. F. R., Heckbert, Susan, Vollenweider, Peter, Hayward, Caroline, Stefansson, Kari, Froguel, Philippe, Groop, Leif J., Wareham, Nicholas M., van Duijn, Cornelia F., Feitosa, Mary J., O'Donnell, Christopher, Kaehoenen, Mika, Perola, Markus, Boehnke, Michael, Kardia, Sharon L. R., Erdmann, Jeanette, Palmer, Colin N. A., Ohlsson, Claes J., Porteous, David G., Eriksson, Johan, Bouchard, Claude, Moebus, Susanne, Kraft, Peter R., Weir, David, Cusi, Daniele, Ferrucci, Luigi, Ulivi, Sheila, Girotto, Giorgia, Correa, Adolfo, Kaeaeb, Stefan, Peters, Annette C., Chambers, John S., Kooner, Jaspal, Maerz, Winfried I., Rotter, Jerome A., Hicks, Andrew, Smith, J. Gustav, Kiemeney, Lambertus A. L. M. O., Mook-Kanamori, Dennis, Penninx, Brenda W. J. H., Gyllensten, Ulf, Wilson, James, Burgess, Stephen, Sundström, Johan, Lieb, Wolfgang, Jukema, J. Wouter, Eijgelsheim, Mark, Lakatta, Edward L. M., Cheng, Ching-Yu, Doerr, Marcus, Wong, Tien-Yin, Sabanayagam, Charumathi J., Oldehinkel, Albertine, Riese, Harriette, Lehtimaeki, Terho, Verweij, Niek, and van der Harst, Pim
Abstract: The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
Published: 2023
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29. The Suicidal Intrusions Attributes Scale (SINAS) : a new tool measuring suicidal intrusions

Author: van Bentum, Jael S., Kerkhof, Ad J. F. M., Huibers, Marcus J. H., Holmes, Emily A., de Geus, Stephan, Sijbrandij, Marit, van Bentum, Jael S., Kerkhof, Ad J. F. M., Huibers, Marcus J. H., Holmes, Emily A., de Geus, Stephan, and Sijbrandij, Marit
Abstract: Introduction: Suicidal intrusions are uncontrollable, intrusive mental images (e. g., visualizing a future suicidal act). They may also be called suicidal "flash-forwards." Despite the importance of integrating the assessment of suicidal intrusions into a clinical routine assessment, quick self-report screening instruments are lacking. This study describes the development of a new instrument-Suicidal Intrusions Attributes Scale (SINAS)-to assess the severity and characteristics of suicidal intrusions and examines its psychometric properties. Method: The sample included currently suicidal outpatients with elevated levels of depression recruited across mental health institutions in the Netherlands (N = 168). Instruments administered were 10-item SINAS, the Suicidal Ideation Attributes Scale (SIDAS), the Prospective Imagery Task (PIT), four-item Suicidal Cognitions Interview (SCI), and the Beck Depression Inventory (BDI-II). Results: An exploratory factor analysis identified a one-factor structure. The resulting SINAS demonstrated good internal consistency (Cronbach's & alpha; = 0.91) and convergent validity, as expected. Discussion: Overall, this study demonstrated acceptable levels of reliability and validity of the measure in a depressed clinical population with suicidal ideation. The SINAS may be a useful screening tool for suicidal intrusions in both research and clinical settings.
Published: 2023
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30. Maternal perception of fetal movements:Views, knowledge and practices of women and health providers in a low-resource setting

Author: Antonio, Carl Abelardo T., Weller, Katinka, Housseine, Natasha, Khamis, Rashid S., Meguid, Tarek, Hofmeyr, G. Justus, Browne, Joyce L., Rijken, Marcus J., Antonio, Carl Abelardo T., Weller, Katinka, Housseine, Natasha, Khamis, Rashid S., Meguid, Tarek, Hofmeyr, G. Justus, Browne, Joyce L., and Rijken, Marcus J.
Abstract: The study assessed perception, knowledge, and practices regarding maternal perception of fetal movements (FMs) among women and their healthcare providers in a low-resource setting. Semi-structured interviews, questionnaires and focus group discussions were conducted with 45 Zanzibar women (18 antenatal, 28 postpartum) and 28 health providers at the maternity unit of Mnazi Mmoja Hospital, Zanzibar, Tanzania. Descriptive and thematic analyses were conducted to systematically extract subthemes within four main themes 1) knowledge/awareness, 2) behavior/practice, 3) barriers, and 4) ways to improve practice. Within the main themes it was found that 1) Women were instinctively aware of (ab)normal FM-patterns and healthcare providers had adequate knowledge about FMs. 2) Women often did not know how to monitor FMs or when to report concerns. There was inadequate assessment and management of (ab)normal FMs. 3) Barriers included the fact that women did not feel free to express concerns. Healthcare providers considered FM-awareness among women as low and unreliable. There was lack of staff, time and space for FM-education, and no protocol for FM-management. 4) Women and health providers recognised the need for education on assessment and management of (ab)normal FMs. In conclusion, women demonstrated adequate understanding of FMs and perceived abnormalities of these movements better than assumed by health providers. There is a need for more evidence on the effect of improving knowledge and awareness of FMs to construct evidence-based guidelines for low resource settings.
Published: 2023

31. Lung Ultrasound Prediction Model for Acute Respiratory Distress Syndrome A Multicenter Prospective Observational Study

Author: Smit, Marry R., Hagens, Laura A., Heijnen, Nanon F. L., Pisani, Luigi, Cherpanath, Thomas G. V., Dongelmans, Dave A., de Grooth, Harm-Jan S., Pierrakos, Charalampos, Tuinman, Pieter Roel, Zimatore, Claudio, Paulus, Frederique, Schnabel, Ronny M., Schultz, Marcus J., Bergmans, Dennis C. J. J., Bos, Lieuwe D. J., DARTS Consortium, Smit, Marry R., Hagens, Laura A., Heijnen, Nanon F. L., Pisani, Luigi, Cherpanath, Thomas G. V., Dongelmans, Dave A., de Grooth, Harm-Jan S., Pierrakos, Charalampos, Tuinman, Pieter Roel, Zimatore, Claudio, Paulus, Frederique, Schnabel, Ronny M., Schultz, Marcus J., Bergmans, Dennis C. J. J., Bos, Lieuwe D. J., and DARTS Consortium
Abstract: Rationale: Lung ultrasound (LUS) is a promising tool for diagnosis of acute respiratory distress syndrome (ARDS), but adequately sized studies with external validation are lacking.Objectives: To develop and validate a data-driven LUS score for diagnosis of ARDS and compare its performance with that of chest radiography (CXR).Methods: This multicenter prospective observational study included invasively ventilated ICU patients who were divided into a derivation cohort and a validation cohort. Three raters scored ARDS according to the Berlin criteria, resulting in a classification of "certain no ARDS," or "certain ARDS" when experts agreed or "uncertain ARDS" when evaluations conflicted. Uncertain cases were classified in a consensus meeting. Results of a 12-region LUS exam were used in a logistic regression model to develop the LUS-ARDS score.Measurements and Main Results: Three hundred twenty-four (16% certain ARDS) and 129 (34% certain ARDS) patients were included in the derivation cohort and the validation cohort, respectively. With an ARDS diagnosis by the expert panel as the reference test, the LUS-ARDS score, including the left and right LUS aeration scores and anterolateral pleural line abnormalities, had an area under the receiver operating characteristic (ROC) curve of 0.90 (95% confidence interval [CI], 0.85-0.95) in certain patients of the derivation cohort and 0.80 (95% CI, 0.72-0.87) in all patients of the validation cohort. Within patients who had imaging-gold standard chest computed tomography available, diagnostic accuracy of eight independent CXR readers followed the ROC curve of the LUS-ARDS score.Conclusions: The LUS-ARDS score can be used to accurately diagnose ARDS also after external validation. The LUS-ARDS score may be a useful adjunct to a diagnosis of ARDS after further validation, as it showed performance comparable with that of the current practice with experienced CXR readers but more objectifiable diagnostic accuracy at each cutoff.
Published: 2023

32. The diagnostic accuracy of lung ultrasound to determine PiCCO-derived extravascular lung water in invasively ventilated patients with COVID-19 ARDS

Author: Atmowihardjo, Leila N., Schippers, Job R., Haaksma, Mark E., Smit, Marry R., Bogaard, Harm J., Heunks, Leo, Juffermans, Nicole P., Schultz, Marcus J., Endeman, Henrik, van Velzen, Patricia, Tuinman, Pieter R., Aman, Jurjan, Bos, Lieuwe D.J., Atmowihardjo, Leila N., Schippers, Job R., Haaksma, Mark E., Smit, Marry R., Bogaard, Harm J., Heunks, Leo, Juffermans, Nicole P., Schultz, Marcus J., Endeman, Henrik, van Velzen, Patricia, Tuinman, Pieter R., Aman, Jurjan, and Bos, Lieuwe D.J.
Abstract: Background: Lung ultrasound (LUS) can detect pulmonary edema and it is under consideration to be added to updated acute respiratory distress syndrome (ARDS) criteria. However, it remains uncertain whether different LUS scores can be used to quantify pulmonary edema in patient with ARDS. Objectives: This study examined the diagnostic accuracy of four LUS scores with the extravascular lung water index (EVLWi) assessed by transpulmonary thermodilution in patients with moderate-to-severe COVID-19 ARDS. Methods: In this predefined secondary analysis of a multicenter randomized-controlled trial (InventCOVID), patients were enrolled within 48 hours after intubation and underwent LUS and EVLWi measurement on the first and fourth day after enrolment. EVLWi and ∆EVLWi were used as reference standards. Two 12-region scores (global LUS and LUS–ARDS), an 8-region anterior–lateral score and a 4-region B-line score were used as index tests. Pearson correlation was performed and the area under the receiver operating characteristics curve (AUROCC) for severe pulmonary edema (EVLWi > 15 mL/kg) was calculated. Results: 26 out of 30 patients (87%) had complete LUS and EVLWi measurements at time point 1 and 24 out of 29 patients (83%) at time point 2. The global LUS (r = 0.54), LUS–ARDS (r = 0.58) and anterior–lateral score (r = 0.54) correlated significantly with EVLWi, while the B-line score did not (r = 0.32). ∆global LUS (r = 0.49) and ∆anterior–lateral LUS (r = 0.52) correlated significantly with ∆EVLWi. AUROCC for EVLWi > 15 ml/kg was 0.73 for the global LUS, 0.79 for the anterior–lateral and 0.85 for the LUS–ARDS score. Conclusions: Overall, LUS demonstrated an acceptable diagnostic accuracy for detection of pulmonary edema in moderate–to–severe COVID-19 ARDS when compared with PICCO. For identifying patients at risk of severe pulmonary edema, an extended score considering p
Published: 2023

33. Antarctic evidence for an abrupt northward shift of the Southern Hemisphere westerlies at 32 ka BP

Author: Venugopal, Abhijith U., Bertler, Nancy A. N., Severinghaus, Jeffrey P., Brook, Edward J., Cortese, Giuseppe, Lee, James E., Blunier, Thomas, Mayewski, Paul A., Kjær, Helle A., Carter, Lionel, Weber, Michael E., Levy, Richard H., Pyne, Rebecca L., Vandergoes, Marcus J., Venugopal, Abhijith U., Bertler, Nancy A. N., Severinghaus, Jeffrey P., Brook, Edward J., Cortese, Giuseppe, Lee, James E., Blunier, Thomas, Mayewski, Paul A., Kjær, Helle A., Carter, Lionel, Weber, Michael E., Levy, Richard H., Pyne, Rebecca L., and Vandergoes, Marcus J.
Published: 2023

34. IGG3 Subclass Antibodies Recognize Antigenically Drifted Influenza Viruses and SARS-CoV-2 Variants Through Efficient Bivalent Binding

Author: Bolton, Marcus J., Santos, Jefferson J.S., Arevalo, Claudia P., Griesman, Trevor, Watson, Megan, Li, Shuk Hang, Bates, Paul, Ramage, Holly, Wilson, Patrick C., Hensley, Scott E., Bolton, Marcus J., Santos, Jefferson J.S., Arevalo, Claudia P., Griesman, Trevor, Watson, Megan, Li, Shuk Hang, Bates, Paul, Ramage, Holly, Wilson, Patrick C., and Hensley, Scott E.
Abstract: The constant domains of antibodies are important for effector functions, but less is known about how they can affect binding and neutralization of viruses. Here, we evaluated a panel of human influenza virus monoclonal antibodies (mAbs) expressed as IgG1, IgG2, or IgG3. We found that many influenza virus-specific mAbs have altered binding and neutralization capacity depending on the IgG subclass encoded and that these differences result from unique bivalency capacities of the subclasses. Importantly, subclass differences in antibody binding and neutralization were greatest when the affinity for the target antigen was reduced through antigenic mismatch. We found that antibodies expressed as IgG3 bound and neutralized antigenically drifted influenza viruses more effectively. We obtained similar results using a panel of SARS-CoV-2-specific mAbs and the antigenically advanced B.1.351 and BA.1 strains of SARS-CoV-2. We found that a licensed therapeutic mAb retained neutralization breadth against SARS-CoV-2 variants when expressed as IgG3, but not IgG1. These data highlight that IgG subclasses are not only important for fine-tuning effector functionality but also for binding and neutralization of antigenically drifted viruses.
Published: 2023

35. Efficacy and safety of intravenous imatinib in COVID-19 ARDS:a randomized, double-blind, placebo-controlled clinical trial

Author: Atmowihardjo, Leila N., Schippers, Job R., Duijvelaar, Erik, Bartelink, Imke H., Bet, Pierre M., Swart, Noortje E.L., van Rein, Nienke, Purdy, Keith, Cavalla, David, McElroy, Andrew, Fritchley, Sarah, Vonk Noordegraaf, Anton, Endeman, Henrik, van Velzen, Patricia, Koopmans, Matty, Bogaard, Harm Jan, Heunks, Leo, Juffermans, Nicole, Schultz, Marcus J., Tuinman, Pieter R., Bos, Lieuwe D.J., Aman, Jurjan, Atmowihardjo, Leila N., Schippers, Job R., Duijvelaar, Erik, Bartelink, Imke H., Bet, Pierre M., Swart, Noortje E.L., van Rein, Nienke, Purdy, Keith, Cavalla, David, McElroy, Andrew, Fritchley, Sarah, Vonk Noordegraaf, Anton, Endeman, Henrik, van Velzen, Patricia, Koopmans, Matty, Bogaard, Harm Jan, Heunks, Leo, Juffermans, Nicole, Schultz, Marcus J., Tuinman, Pieter R., Bos, Lieuwe D.J., and Aman, Jurjan
Abstract: Purpose: A hallmark of acute respiratory distress syndrome (ARDS) is hypoxaemic respiratory failure due to pulmonary vascular hyperpermeability. The tyrosine kinase inhibitor imatinib reversed pulmonary capillary leak in preclinical studies and improved clinical outcomes in hospitalized COVID-19 patients. We investigated the effect of intravenous (IV) imatinib on pulmonary edema in COVID-19 ARDS. Methods: This was a multicenter, randomized, double-blind, placebo-controlled trial. Invasively ventilated patients with moderate-to-severe COVID-19 ARDS were randomized to 200 mg IV imatinib or placebo twice daily for a maximum of seven days. The primary outcome was the change in extravascular lung water index (∆EVLWi) between days 1 and 4. Secondary outcomes included safety, duration of invasive ventilation, ventilator-free days (VFD) and 28-day mortality. Posthoc analyses were performed in previously identified biological subphenotypes. Results: 66 patients were randomized to imatinib (n = 33) or placebo (n = 33). There was no difference in ∆EVLWi between the groups (0.19 ml/kg, 95% CI − 3.16 to 2.77, p = 0.89). Imatinib treatment did not affect duration of invasive ventilation (p = 0.29), VFD (p = 0.29) or 28-day mortality (p = 0.79). IV imatinib was well-tolerated and appeared safe. In a subgroup of patients characterized by high IL-6, TNFR1 and SP-D levels (n = 20), imatinib significantly decreased EVLWi per treatment day (− 1.17 ml/kg, 95% CI − 1.87 to − 0.44). Conclusions: IV imatinib did not reduce pulmonary edema or improve clinical outcomes in invasively ventilated COVID-19 patients. While this trial does not support the use of imatinib in the general COVID-19 ARDS population, imatinib reduced pulmonary edema in a subgroup of patients, underscoring the potential value of predictive enrichment in ARDS trials. Trial registration NCT04794088 , registered 11 March 2021. European Clinical Trials Database (EudraCT number: 2020-005447-23).
Published: 2023

36. Optimal Dosing and Timing of High-Dose Corticosteroid Therapy in Hospitalized Patients With COVID-19:Study Protocol for a Retrospective Observational Multicenter Study (SELECT)

Author: Daenen, Katrijn, Huijben, Jilske A., Boyd, Anders, Bos, Lieuwe D.J., Stoof, Sara C.M., van Willigen, Hugo, Gommers, Diederik A.M.P.J., Moeniralam, Hazra S., den Uil, Corstiaan A., Juffermans, Nicole P., Kant, Merijn, Valkenburg, Abraham J., Pillay, Janesh, van Meenen, David M.P., Paulus, Frederique, Schultz, Marcus J., Dalm, Virgil A.S.H., van Gorp, Eric C.M., Schinkel, Janke, Endeman, Henrik, Daenen, Katrijn, Huijben, Jilske A., Boyd, Anders, Bos, Lieuwe D.J., Stoof, Sara C.M., van Willigen, Hugo, Gommers, Diederik A.M.P.J., Moeniralam, Hazra S., den Uil, Corstiaan A., Juffermans, Nicole P., Kant, Merijn, Valkenburg, Abraham J., Pillay, Janesh, van Meenen, David M.P., Paulus, Frederique, Schultz, Marcus J., Dalm, Virgil A.S.H., van Gorp, Eric C.M., Schinkel, Janke, and Endeman, Henrik
Abstract: Background: In hospitalized patients with COVID-19, the dosing and timing of corticosteroids vary widely. Low-dose dexamethasone therapy reduces mortality in patients requiring respiratory support, but it remains unclear how to treat patients when this therapy fails. In critically ill patients, high-dose corticosteroids are often administered as salvage late in the disease course, whereas earlier administration may be more beneficial in preventing disease progression. Previous research has revealed that increased levels of various biomarkers are associated with mortality, and whole blood transcriptome sequencing has the ability to identify host factors predisposing to critical illness in patients with COVID-19. Objective: Our goal is to determine the most optimal dosing and timing of corticosteroid therapy and to provide a basis for personalized corticosteroid treatment regimens to reduce morbidity and mortality in hospitalized patients with COVID-19. Methods: This is a retrospective, observational, multicenter study that includes adult patients who were hospitalized due to COVID-19 in the Netherlands. We will use the differences in therapeutic strategies between hospitals (per protocol high-dose corticosteroids or not) over time to determine whether high-dose corticosteroids have an effect on the following outcome measures: mechanical ventilation or high-flow nasal cannula therapy, in-hospital mortality, and 28-day survival. We will also explore biomarker profiles in serum and bronchoalveolar lavage fluid and use whole blood transcriptome analysis to determine factors that influence the relationship between high-dose corticosteroids and outcome. Existing databases that contain routinely collected electronic data during ward and intensive care admissions, as well as existing biobanks, will be used. We will apply longitudinal modeling appropriate for each data structure to answer the research questions at hand. Results: As of April 2023, data have been collected f
Published: 2023

37. Adaptive Spectral Inversion for Inverse Medium Problems

Author: Gleichmann, Yannik G., Grote, Marcus J., Gleichmann, Yannik G., and Grote, Marcus J.
Abstract: A nonlinear optimization method is proposed for the solution of inverse medium problems with spatially varying properties. To avoid the prohibitively large number of unknown control variables resulting from standard grid-based representations, the misfit is instead minimized in a small subspace spanned by the first few eigenfunctions of a judicious elliptic operator, which itself depends on the previous iteration. By repeatedly adapting both the dimension and the basis of the search space, regularization is inherently incorporated at each iteration without the need for extra Tikhonov penalization. Convergence is proved under an angle condition, which is included into the resulting \emph{Adaptive Spectral Inversion} (ASI) algorithm. The ASI approach compares favorably to standard grid-based inversion using $L^2$-Tikhonov regularization when applied to an elliptic inverse problem. The improved accuracy resulting from the newly included angle condition is further demonstrated via numerical experiments from time-dependent inverse scattering problems.
Published: 2023

38. Management of unexpected placenta accreta spectrum cases in resource-poor settings

Author: Aryananda, Rozi Aditya, Nieto-Calvache, Albaro José, Duvekot, Johannes J., Aditiawarman, Aditiawarman, Rijken, Marcus J., Aryananda, Rozi Aditya, Nieto-Calvache, Albaro José, Duvekot, Johannes J., Aditiawarman, Aditiawarman, and Rijken, Marcus J.
Abstract: BACKGROUND: On a global scale, cases of placenta accreta spectrum are often just identified during cesarean delivery because they are missed during antenatal care screening. Routine operating teams not trained in the management of placenta accreta spectrum are faced with difficult surgical situations and have to make decisions that may define the clinical outcomes. Although there are general recommendations for the intraoperative management of placenta accreta spectrum, no studies have described the clinical reality of unexpected placenta accreta spectrum cases in resource-poor settings. OBJECTIVE: This study aimed to describe the maternal outcomes of previously undiagnosed placenta accreta spectrum managed in resource-poor settings in Colombia and Indonesia. STUDY DESIGN: This was a retrospective case series of women with histologically confirmed placenta accreta spectrum treated in 2 placenta accreta spectrum centers after referral from remote resource-poor hospitals. Clinical outcomes were analyzed according to the initial type of management: (1) no cesarean delivery; (2) placenta left in situ after cesarean delivery; (3) partial removal of the placenta after cesarean delivery; and (4) post–cesarean hysterectomy. In addition, we evaluated the use of telemedicine by comparing the outcomes of women in hospitals that used the support of the placenta accreta spectrum center during the initial surgery. RESULTS: A total of 29 women who were initially managed in Colombia (n=2) and Indonesia (n=27) were included. The lowest volume of blood loss and the lowest frequency of complications were in women who underwent deferred cesarean delivery (n=5; 17.2%) and in those who had a delayed placental delivery (n=5; 20.7%). Five maternal deaths (14%) occurred in the group that did not receive telehelp, and 4 women died of irreversible shock because of uncontrolled bleeding. CONCLUSION: Previously undiagnosed placenta accreta spectrum in resource-poor hospitals was associated w
Published: 2023

39. Effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients (CONFIDENCE):protocol for a multicentre randomised controlled trial

Author: Blok, Siebe G., Mousa, Amne, Brouwer, Michelle G., de Grooth, Harm Jan, Neto, Ary Serpa, Blans, Michiel J., den Boer, Sylvia, Dormans, Tom, Endeman, Henrik, Roeleveld, Timo, Scholten, Harm, van Slobbe-Bijlsma, Eline R., Scholten, Erik, Touw, Hugo, van der Ven, Fleur Stefanie L.I.M., Wils, Evert Jan, van Westerloo, David J., Heunks, Leo M.A., Schultz, Marcus J., Paulus, Frederique, Tuinman, Pieter R., Blok, Siebe G., Mousa, Amne, Brouwer, Michelle G., de Grooth, Harm Jan, Neto, Ary Serpa, Blans, Michiel J., den Boer, Sylvia, Dormans, Tom, Endeman, Henrik, Roeleveld, Timo, Scholten, Harm, van Slobbe-Bijlsma, Eline R., Scholten, Erik, Touw, Hugo, van der Ven, Fleur Stefanie L.I.M., Wils, Evert Jan, van Westerloo, David J., Heunks, Leo M.A., Schultz, Marcus J., Paulus, Frederique, and Tuinman, Pieter R.
Abstract: Background: Fluid therapy is a common intervention in critically ill patients. It is increasingly recognised that deresuscitation is an essential part of fluid therapy and delayed deresuscitation is associated with longer invasive ventilation and length of intensive care unit (ICU) stay. However, optimal timing and rate of deresuscitation remain unclear. Lung ultrasound (LUS) may be used to identify fluid overload. We hypothesise that daily LUS-guided deresuscitation is superior to deresuscitation without LUS in critically ill patients expected to undergo invasive ventilation for more than 24 h in terms of ventilator free-days and being alive at day 28. Methods: The “effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients” (CONFIDENCE) is a national, multicentre, open-label, randomised controlled trial (RCT) in adult critically ill patients that are expected to be invasively ventilated for at least 24 h. Patients with conditions that preclude a negative fluid balance or LUS examination are excluded. CONFIDENCE will operate in 10 ICUs in the Netherlands and enrol 1000 patients. After hemodynamic stabilisation, patients assigned to the intervention will receive daily LUS with fluid balance recommendations. Subjects in the control arm are deresuscitated at the physician’s discretion without the use of LUS. The primary endpoint is the number of ventilator-free days and being alive at day 28. Secondary endpoints include the duration of invasive ventilation; 28-day mortality; 90-day mortality; ICU, in hospital and total length of stay; cumulative fluid balance on days 1–7 after randomisation and on days 1–7 after start of LUS examination; mean serum lactate on days 1–7; the incidence of reintubations, chest drain placement, atrial fibrillation, kidney injury (KDIGO stadium ≥ 2) and hypernatremia; the use of invasive hemodynamic monitoring, and chest-X-ray; and quality of life at day 28. Discussion: The CONFIDENC
Published: 2023

40. Effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients (CONFIDENCE): protocol for a multicentre randomised controlled trial

Author: Blok, Siebe G., Mousa, Amne, Brouwer, Michelle G., de Grooth, Harm Jan, Neto, Ary Serpa, Blans, Michiel J., den Boer, Sylvia, Dormans, Tom, Endeman, Henrik, Roeleveld, Timo, Scholten, Harm, van Slobbe-Bijlsma, Eline R., Scholten, Erik, Touw, Hugo, van der Ven, Fleur Stefanie L.I.M., Wils, Evert Jan, van Westerloo, David J., Heunks, Leo M.A., Schultz, Marcus J., Paulus, Frederique, Tuinman, Pieter R., Blok, Siebe G., Mousa, Amne, Brouwer, Michelle G., de Grooth, Harm Jan, Neto, Ary Serpa, Blans, Michiel J., den Boer, Sylvia, Dormans, Tom, Endeman, Henrik, Roeleveld, Timo, Scholten, Harm, van Slobbe-Bijlsma, Eline R., Scholten, Erik, Touw, Hugo, van der Ven, Fleur Stefanie L.I.M., Wils, Evert Jan, van Westerloo, David J., Heunks, Leo M.A., Schultz, Marcus J., Paulus, Frederique, and Tuinman, Pieter R.
Abstract: Background: Fluid therapy is a common intervention in critically ill patients. It is increasingly recognised that deresuscitation is an essential part of fluid therapy and delayed deresuscitation is associated with longer invasive ventilation and length of intensive care unit (ICU) stay. However, optimal timing and rate of deresuscitation remain unclear. Lung ultrasound (LUS) may be used to identify fluid overload. We hypothesise that daily LUS-guided deresuscitation is superior to deresuscitation without LUS in critically ill patients expected to undergo invasive ventilation for more than 24 h in terms of ventilator free-days and being alive at day 28. Methods: The “effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients” (CONFIDENCE) is a national, multicentre, open-label, randomised controlled trial (RCT) in adult critically ill patients that are expected to be invasively ventilated for at least 24 h. Patients with conditions that preclude a negative fluid balance or LUS examination are excluded. CONFIDENCE will operate in 10 ICUs in the Netherlands and enrol 1000 patients. After hemodynamic stabilisation, patients assigned to the intervention will receive daily LUS with fluid balance recommendations. Subjects in the control arm are deresuscitated at the physician’s discretion without the use of LUS. The primary endpoint is the number of ventilator-free days and being alive at day 28. Secondary endpoints include the duration of invasive ventilation; 28-day mortality; 90-day mortality; ICU, in hospital and total length of stay; cumulative fluid balance on days 1–7 after randomisation and on days 1–7 after start of LUS examination; mean serum lactate on days 1–7; the incidence of reintubations, chest drain placement, atrial fibrillation, kidney injury (KDIGO stadium ≥ 2) and hypernatremia; the use of invasive hemodynamic monitoring, and chest-X-ray; and quality of life at day 28. Discussion: The CONFIDENC
Published: 2023

41. De-novo reconstruction and identification of transcriptional gene regulatory network modules differentiating single-cell clusters

Author: Oubounyt, Mhaned, Elkjaer, Maria L., Laske, Tanja, Grønning, Alexander G.B., Moeller, Marcus J, Baumbach, Jan, Oubounyt, Mhaned, Elkjaer, Maria L., Laske, Tanja, Grønning, Alexander G.B., Moeller, Marcus J, and Baumbach, Jan
Abstract: Single-cell RNA sequencing (scRNA-seq) technology provides an unprecedented opportunity to understand gene functions and interactions at single-cell resolution. While computational tools for scRNA-seq data analysis to decipher differential gene expression profiles and differential pathway expression exist, we still lack methods to learn differential regulatory disease mechanisms directly from the single-cell data. Here, we provide a new methodology, named DiNiro, to unravel such mechanisms de novo and report them as small, easily interpretable transcriptional regulatory network modules. We demonstrate that DiNiro is able to uncover novel, relevant, and deep mechanistic models that not just predict but explain differential cellular gene expression programs. DiNiro is available at https://exbio.wzw.tum.de/diniro/.
Published: 2023

42. Fetal movement trials:Where is the evidence in settings with a high burden of stillbirths?

Author: Housseine, Natasha, Browne, Joyce, Maaloe, Nanna, Dmello, Brenda Sequeira, Ali, Sam, Abeid, Muzdalifat, Meguid, Tarek, Rijken, Marcus J., Kidanto, Hussein, Housseine, Natasha, Browne, Joyce, Maaloe, Nanna, Dmello, Brenda Sequeira, Ali, Sam, Abeid, Muzdalifat, Meguid, Tarek, Rijken, Marcus J., and Kidanto, Hussein
Abstract: Fetal movement (FM) is a sign of fetal life and wellbeing that is felt by the pregnant woman, and reduced FM is known to precede stillbirths.1, 2 Therefore, healthcare providers may advise women to monitor and report if their babies’ movements are fewer than usual. In high-income countries (HICs), there has been a renewed interest in FM with a recent wave of large-scale randomised controlled clinical trials investigating its potential to reduce stillbirths. The My Baby’s Movement trial in Australia and New Zealand and the Mindfetalness trial in Sweden have investigated the effects of intervention aimed at increasing women’s awareness of FM.3, 4 In the UK, the AFFIRM trial investigated the effects of an FM awareness package coupled with a standardised management protocol.5 The ongoing CEPRA study in the Netherlands, UK and Australia aims to evaluate Cerebro Placental Ratio as an indicator for delivery in women with reduced FM.6 None of the completed trials, however, found significant reductions in stillbirths. Moreover, they showed conflicting results on some potential harmful consequences, such as increased rates of obstetric interventions. In this commentary, we reflect on these trials through a global lens, and we urgently call for more trials – but this time in settings suffering the majority (98%) of the world’s 2 million annual stillbirths
Published: 2023

43. Malaria Infections and Placental Blood Flow: A Doppler Ultrasound Study From a Preconception Cohort in Benin

Author: MS Verloskunde, Cancer, Mondeilh, Aude, Yovo, Emmanuel, Accrombessi, Manfred, Hounkonnou, Cornelia, Agbota, Gino, Atade, William, Ladikpo, Olaiitan T, Mehoba, Murielle, Degbe, Auguste, Vianou, Bertin, Sossou, Dariou, Ndam, Nicaise Tuikue, Massougbodji, Achille, McGready, Rose, Fievet, Nadine, Rijken, Marcus J, Cottrell, Gilles, Briand, Valérie, MS Verloskunde, Cancer, Mondeilh, Aude, Yovo, Emmanuel, Accrombessi, Manfred, Hounkonnou, Cornelia, Agbota, Gino, Atade, William, Ladikpo, Olaiitan T, Mehoba, Murielle, Degbe, Auguste, Vianou, Bertin, Sossou, Dariou, Ndam, Nicaise Tuikue, Massougbodji, Achille, McGready, Rose, Fievet, Nadine, Rijken, Marcus J, Cottrell, Gilles, and Briand, Valérie
Published: 2023

44. Severe falciparum malaria in pregnancy in Southeast Asia: a multi-centre retrospective cohort study

Author: MS Verloskunde, Cancer, Saito, Makoto, Phyo, Aung Pyae, Chu, Cindy, Proux, Stephane, Rijken, Marcus J, Beau, Candy, Win, Htun Htun, Archasuksan, Laypaw, Wiladphaingern, Jacher, Phu, Nguyen H, Hien, Tran T, Day, Nick P, Dondorp, Arjen M, White, Nicholas J, Nosten, François, McGready, Rose, MS Verloskunde, Cancer, Saito, Makoto, Phyo, Aung Pyae, Chu, Cindy, Proux, Stephane, Rijken, Marcus J, Beau, Candy, Win, Htun Htun, Archasuksan, Laypaw, Wiladphaingern, Jacher, Phu, Nguyen H, Hien, Tran T, Day, Nick P, Dondorp, Arjen M, White, Nicholas J, Nosten, François, and McGready, Rose
Published: 2023

45. Evaluation of the Emergency Obstetric and Newborn Care training in Gondar, Ethiopia; a mixed methods study

Author: MS Verloskunde, Cancer, Hulsbergen, Myrrith, Abera, Birhanu, Adefris, Mulat, Kassahun, Dawit, Meulenbeld, Marieke, van Nievelt, Sabine, Ameh, Charles, Bruinooge, Mimosa, Rijken, Marcus J, Stekelenburg, Jelle, MS Verloskunde, Cancer, Hulsbergen, Myrrith, Abera, Birhanu, Adefris, Mulat, Kassahun, Dawit, Meulenbeld, Marieke, van Nievelt, Sabine, Ameh, Charles, Bruinooge, Mimosa, Rijken, Marcus J, and Stekelenburg, Jelle
Published: 2023

46. Correction: ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia (Intensive Care Medicine, (2023), 49, 6, (615-632), 10.1007/s00134-023-07033-8)

Author: Medische Staf Intensive Care, Infection & Immunity, Martin-Loeches, Ignacio, Torres, Antoni, Nagavci, Blin, Aliberti, Stefano, Antonelli, Massimo, Bassetti, Matteo, Bos, Lieuwe D., Chalmers, James D., Derde, Lennie, De Waele, Jan, Garnacho-Montero, Jose, Kollef, Marin, Luna, Carlos M., Menendez, Rosario, Niederman, Michael S., Ponomarev, Dmitry, Restrepo, Marcos I., Rigau, David, Schultz, Marcus J., Weiss, Emmanuel, Welte, Tobias, Wunderink, Richard, Medische Staf Intensive Care, Infection & Immunity, Martin-Loeches, Ignacio, Torres, Antoni, Nagavci, Blin, Aliberti, Stefano, Antonelli, Massimo, Bassetti, Matteo, Bos, Lieuwe D., Chalmers, James D., Derde, Lennie, De Waele, Jan, Garnacho-Montero, Jose, Kollef, Marin, Luna, Carlos M., Menendez, Rosario, Niederman, Michael S., Ponomarev, Dmitry, Restrepo, Marcos I., Rigau, David, Schultz, Marcus J., Weiss, Emmanuel, Welte, Tobias, and Wunderink, Richard
Published: 2023

47. Exploring the shared decision making process of caesarean sections at a teaching hospital in Ghana: a mixed methods study

Author: MS Verloskunde, Child Health, Global Health, Circulatory Health, Cancer, Asah-Opoku, Kwaku, Onisarotu, Aisha N, Nuamah, Mercy A, Syurina, Elena, Bloemenkamp, Kitty, Browne, Joyce L, Rijken, Marcus J, MS Verloskunde, Child Health, Global Health, Circulatory Health, Cancer, Asah-Opoku, Kwaku, Onisarotu, Aisha N, Nuamah, Mercy A, Syurina, Elena, Bloemenkamp, Kitty, Browne, Joyce L, and Rijken, Marcus J
Published: 2023

48. Vacuum extraction or caesarean section in the second stage of labour: A systematic review

Author: MS Verloskunde, Child Health, Cardiometabolic Health, Thierens, Stephanie, van Binsbergen, Annelien, Nolens, Barbara, van den Akker, Thomas, Bloemenkamp, Kitty, Rijken, Marcus J., MS Verloskunde, Child Health, Cardiometabolic Health, Thierens, Stephanie, van Binsbergen, Annelien, Nolens, Barbara, van den Akker, Thomas, Bloemenkamp, Kitty, and Rijken, Marcus J.
Published: 2023

49. Management of unexpected placenta accreta spectrum cases in resource-poor settings

Author: MS Verloskunde, Aryananda, Rozi Aditya, Nieto-Calvache, Albaro José, Duvekot, Johannes J, Aditiawarman, Aditiawarman, Rijken, Marcus J, MS Verloskunde, Aryananda, Rozi Aditya, Nieto-Calvache, Albaro José, Duvekot, Johannes J, Aditiawarman, Aditiawarman, and Rijken, Marcus J
Published: 2023

50. Maternal perception of fetal movements: Views, knowledge and practices of women and health providers in a low-resource setting

Author: MS Verloskunde, Global Health, Child Health, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Weller, Katinka, Housseine, Natasha, Khamis, Rashid S, Meguid, Tarek, Hofmeyr, G Justus, Browne, Joyce L, Rijken, Marcus J, MS Verloskunde, Global Health, Child Health, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Weller, Katinka, Housseine, Natasha, Khamis, Rashid S, Meguid, Tarek, Hofmeyr, G Justus, Browne, Joyce L, and Rijken, Marcus J
Published: 2023

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