629 results on '"Christian, Martin"'
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2. Identifying trigger cues for hospital blood transfusions based on ensemble of machine learning methods
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Eva V. Zadorozny, Tyler Weigel, Samuel M. Galvagno, Christian Martin-Gill, Joshua B. Brown, and Francis X. Guyette
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Prehospital transfusion ,Early hospital transfusion ,Hemorrhagic shock ,Prehospital lactate concentration ,Fast frugal trees ,Bayesian analysis ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Background Traumatic shock is the leading cause of preventable death with most patients dying within the first six hours from arriving to the hospital. This underscores the importance of prehospital interventions, and growing evidence suggests prehospital transfusion improves survival. Optimizing transfusion triggers in the prehospital setting is key to improving outcomes for patients in hemorrhagic shock. Our objective was to identify factors associated with early in-hospital transfusion requirements available to prehospital clinicians in the field to develop a simple algorithm for prehospital transfusion, particularly for patients with occult shock. Methods We included trauma patients transported by a single critical care transport service to a level I trauma center between 2012 and 2019. We used logistic regression, Fast and Frugal Trees (FFTs), and Bayesian analysis to identify factors associated with early in-hospital blood transfusion as a potential trigger for prehospital transfusion. Results We included 2,157 patients transported from the scene or emergency department (ED) of whom 207 (9.60%) required blood transfusion within four hours of admission. The mean age was 47 (IQR = 28 – 62) and 1,480 (68.6%) patients were male. From 13 clinically relevant factors for early hospital transfusions, four were incorporated into the FFT in following order: 1) SBP, 2) prehospital lactate concentration, 3) Shock Index, 4) AIS of chest (sensitivity = 0.81, specificity = 0.71). The chosen thresholds were similar to conventional ones. Using conventional thresholds resulted in lower model sensitivity. Consistently, prehospital lactate was among most decisive factors of hospital transfusions identified by Bayesian analysis (OR = 2.31; 95% CI 1.55 – 3.37). Conclusions Using an ensemble of frequentist statistics, Bayesian analysis and machine learning, we developed a simple, clinically relevant prehospital algorithm to help identify patients requiring transfusion within 4 h of hospital arrival.
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- 2024
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3. Flying low and slow: Application of algorithmic climate change functions to assess the climate mitigation potential of reduced cruise altitudes and speeds on different days
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Zarah Lea Zengerling, Florian Linke, Christian Martin Weder, Simone Dietmüller, Sigrun Matthes, and Patrick Peter
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aviation climate impact ,operational improvements ,trajectory modelling ,non‑co ,contrail effects ,Meteorology. Climatology ,QC851-999 - Abstract
The climate effect from aviation's non‑CO2 emissions such as contrail cirrus, water vapor and nitrogen oxide induced ozone and methane changes depend on emission location and time. Among other approaches, the resulting climate effect can be reduced by lowering cruise flight levels. However, aircraft typically aim to fly at optimum altitudes and perform step climbs with increasing flight length to enhance fuel efficiency and reduce operating cost, what also limits climate effects from CO2 emissions. To account for this and to reduce the overall climate effect of flights, the higher fuel consumption at lower flight altitudes can be compensated by also reducing flight speeds. Therefore, this study analyzes the mitigation potential of flying lower and slower with regard to the overall climate effect along flight trajectories. Specifically, actually flown point profiles are combined with related meteorological parameters to evaluate the effect from reduced cruise altitudes and speeds with an updated set of prototype algorithmic climate change functions. Different case studies show varying effects for individual days during different seasons, and significant mitigation potentials due to flying lower and slower can be observed (up to 9 % on a summer day and 16 % on a winter day). A sensitivity study to explore uncertainties with regard to the quantification of contrail effects is performed as well as an investigation on possible economic consequences in terms of changes in direct operating cost and eco-efficient solutions.
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- 2024
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4. Clinical features and treatment outcomes of bone and joint nontuberculous mycobacterial infections according to immune status: a 9-year retrospective observational cohort
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Pascale Bémer, Alexandra Aubry, Frédéric Schramm, Christelle Koebel, Hélène Revillet, Virginie Baltes, Cécile Le Brun, Pascal Chazerain, Valérie Zeller, Farida Hamdad, Philippe C. Morand, Aurélie Guillouzouic, Caroline Piau, Anne-Laure Roux, Sarah Soueges, Christian Martin, Alice Gaudart, Sophie Hüssler, Vincent Fihman, Anne Carricajo, Christelle Guillet Caruba, Julien Bador, Frédéric-Antoine Dauchy, Hervé Dutronc, Carole Vignals, and Olivia Peuchant
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Non-tuberculous mycobacteria ,Bone and joint infection ,Immune status ,Clinical characteristics ,Outcomes ,Infectious and parasitic diseases ,RC109-216 - Abstract
Objectives: Nontuberculous mycobacteria (NTM) bone and joint infections (BJIs) are uncommon. We evaluated the characteristics of BJIs and identified differences according to immune status. Methods: We performed a multicenter retrospective study in France involving patients with documented NTM BJI over a 9-year period. We collected the clinical and microbiological characteristics, management, and clinical outcomes of the patients. Results: Overall, 95 patients were included, of whom 50.5% (48/95) were immunosuppressed. Tenosynovitis was more frequent in the immunocompetent group, and native arthritis more common in the immunosuppressed group. Mycobacerium marinum and M. abscessus complex were significantly more frequent in the immunocompetent group, and M. avium and M. xenopi were significantly more frequent in the immunosuppressed group. The combination of antibiotherapy with surgery tended to be more frequent in the immunocompetent than the immunosuppressed group (63.8% (30/47) vs 47.8% (22/46), respectively); of the latter, 45.7% (21/46) received antimicrobial therapy alone, a higher frequency than in the immunocompetent group (23.4%, 11/47). The median duration of antimicrobial treatment was similar in the two groups (11 months). Mortality was significantly higher in the immunosuppressed group. Conclusions: Although the clinical presentations and the NTM species involved in BJI differed according to immune status, most recovered completely after treatment.
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- 2024
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5. Machine learning algorithms predict canine structural epilepsy with high accuracy
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Thomas Flegel, Anja Neumann, Anna-Lena Holst, Olivia Kretzschmann, Shenja Loderstedt, Carina Tästensen, Sarah Gutmann, Josephine Dietzel, Lisa Franziska Becker, Theresa Kalliwoda, Vivian Weiß, Madlene Kowarik, Irene Christine Böttcher, and Christian Martin
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dog ,seizures ,artificial intelligence ,Random Forest ,Bayesian Network ,feature selection ,Veterinary medicine ,SF600-1100 - Abstract
IntroductionClinical reasoning in veterinary medicine is often based on clinicians’ personal experience in combination with information derived from publications describing cohorts of patients. Studies on the use of scientific methods for patient individual decision making are largely lacking. This applies to the prediction of the individual underlying pathology in seizuring dogs as well. The aim of this study was to apply machine learning to the prediction of the risk of structural epilepsy in dogs with seizures.Materials and methodsDogs with a history of seizures were retrospectively as well as prospectively included. Data about clinical history, neurological examination, diagnostic tests performed as well as the final diagnosis were collected. For data analysis, the Bayesian Network and Random Forest algorithms were used. A total of 33 features for Random Forest and 17 for Bayesian Network were available for analysis. The following four feature selection methods were applied to select features for further analysis: Permutation Importance, Forward Selection, Random Selection and Expert Opinion. The two algorithms Bayesian Network and Random Forest were trained to predict structural epilepsy using the selected features.ResultsA total of 328 dogs of 119 different breeds were identified retrospectively between January 2017 and June 2021, of which 33.2% were diagnosed with structural epilepsy. An overall of 89,848 models were trained. The Bayesian Network in combination with the Random feature selection performed best. It was able to predict structural epilepsy with an accuracy of 0.969 (sensitivity: 0.857, specificity: 1.000) among all dogs with seizures using the following features: age at first seizure, cluster seizures, seizure in last 24 h, seizure in last 6 month, and seizure in last year.ConclusionMachine learning algorithms such as Bayesian Networks and Random Forests identify dogs with structural epilepsy with a high sensitivity and specificity. This information could provide some guidance to clinicians and pet owners in their clinical decision-making process.
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- 2024
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6. Description and Cross-Sectional Analyses of 25,880 Adults and Children in the UK National Registry of Rare Kidney Diseases Cohort
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Abat, Sharirose, Adalat, Shazia, Agbonmwandolor, Joy, Ahmad, Zubaidah, Alejmi, Abdulfattah, Almasarwah, Rashid, Annear, Nicholas, Asgari, Ellie, Ayers, Amanda, Baharani, Jyoti, Balasubramaniam, Gowrie, Kpodo, Felix Jo-Bamba, Bansal, Tarun, Barratt, Alison, Barratt, Jonathan, Bates, Megan, Bayne, Natalie, Bendle, Janet, Benyon, Sarah, Bergmann, Carsten, Bhandari, Sunil, Bingham, Coralie, Boddana, Preetham, Bond, Sally, Braddon, Fiona, Bramham, Kate, Branson, Angela, Brearey, Stephen, Brocklebank, Vicky, Budwal, Sharanjit, Byrne, Conor, Cairns, Hugh, Camilleri, Brian, Campbell, Gary, Capell, Alys, Carmody, Margaret, Carson, Marion, Cathcart, Tracy, Catley, Christine, Cesar, Karine, Chan, Melanie, Chea, Houda, Chess, James, Cheung, Chee Kay, Chick, Katy-Jane, Chitalia, Nihil, Christian, Martin, Chrysochou, Tina, Clark, Katherine, Clayton, Christopher, Clissold, Rhian, Cockerill, Helen, Coelho, Joshua, Colby, Elizabeth, Colclough, Viv, Conway, Eileen, Cook, H. Terence, Cook, Wendy, Cooper, Theresa, Coward, Richard J., Crosbie, Sarah, Cserep, Gabor, Date, Anjali, Davidson, Katherine, Davies, Amanda, Dhaun, Neeraj, Dhaygude, Ajay, Diskin, Lynn, Dixit, Abhijit, Doctolero, Eunice Ann, Dorey, Suzannah, Downard, Lewis, Drayson, Mark, Dreyer, Gavin, Dutt, Tina, Etuk, Kufreabasi, Evans, Dawn, Finch, Jenny, Flinter, Frances, Fotheringham, James, Francis, Lucy, Gale, Daniel P., Gallagher, Hugh, Game, David, Garcia, Eva Lozano, Gavrila, Madita, Gear, Susie, Geddes, Colin, Gilchrist, Mark, Gittus, Matt, Goggolidou, Paraskevi, Goldsmith, Christopher, Gooden, Patricia, Goodlife, Andrea, Goodwin, Priyanka, Grammatikopoulos, Tassos, Gray, Barry, Griffith, Megan, Gumus, Steph, Gupta, Sanjana, Hamilton, Patrick, Harper, Lorraine, Harris, Tess, Haskell, Louise, Hayward, Samantha, Hegde, Shivaram, Hendry, Bruce, Hewins, Sue, Hewitson, Nicola, Hillman, Kate, Hiremath, Mrityunjay, Howson, Alexandra, Htet, Zay, Huish, Sharon, Hull, Richard, Humphries, Alister, Hunt, David P.J., Hunter, Karl, Hunter, Samantha, Ijeomah-Orji, Marilyn, Inston, Nick, Jayne, David, Jenfa, Gbemisola, Jenkins, Alison, Johnson, Sally, Jones, Caroline A., Jones, Colin, Jones, Amanda, Jones, Rachel, Kamesh, Lavanya, Kanigicherla, Durga, Frankl, Fiona Karet, Karim, Mahzuz, Kaur, Amrit, Kavanagh, David, Kearley, Kelly, Kerecuk, Larissa, Khwaja, Arif, King, Garry, King, Grant, Kislowska, Ewa, Klata, Edyta, Kokocinska, Maria, Lambie, Mark, Lawless, Laura, Ledson, Thomas, Lennon, Rachel, Levine, Adam P., Maggie Lai, Ling Wai, Lipkin, Graham, Lovitt, Graham, Lyons, Paul, Mabillard, Holly, Mackintosh, Katherine, Mahdi, Khalid, Maher, Eamonn, Marchbank, Kevin J., Mark, Patrick B., Masoud, Sherry, Masunda, Bridgett, Mavani, Zainab, Mayfair, Jake, McAdoo, Stephen, Mckinnell, Joanna, Melhem, Nabil, Meyrick, Simon, Moochhala, Shabbir, Morgan, Putnam, Morgan, Ann, Muhammad, Fawad, Murray, Shona, Novobritskaya, Kristina, Ong, Albert CM., Oni, Louise, Osmaston, Kate, Padmanabhan, Neal, Parkes, Sharon, Patrick, Jean, Pattison, James, Paul, Riny, Percival, Rachel, Perkins, Stephen J., Persu, Alexandre, Petchey, William G., Pickering, Matthew C., Pinney, Jennifer, Pitcher, David, Plumb, Lucy, Plummer, Zoe, Popoola, Joyce, Post, Frank, Power, Albert, Pratt, Guy, Pusey, Charles, Rabara, Ria, Rabuya, May, Raju, Tina, Javier, Chadd, Roberts, Ian SD., Roufosse, Candice, Rumjon, Adam, Salama, Alan, Saleem, Moin, Sandford, R.N., Sandu, Kanwaljit S., Sarween, Nadia, Sayer, John A., Sebire, Neil, Selvaskandan, Haresh, Shah, Sapna, Sharma, Asheesh, Sharples, Edward J., Sheerin, Neil, Shetty, Harish, Shroff, Rukshana, Simms, Roslyn, Sinha, Manish, Sinha, Smeeta, Smith, Kerry, Smith, Lara, Srivastava, Shalabh, Steenkamp, Retha, Stott, Ian, Stroud, Katerina, Swift, Pauline, Szklarzewicz, Justyna, Tam, Fred, Tan, Kay, Taylor, Robert, Tischkowitz, Marc, Thomas, Kay, Tse, Yincent, Turnbull, Alison, Turner, A. Neil, Tyerman, Kay, Usher, Miranda, Venkat-Raman, Gopalakrishnan, Walker, Alycon, Walsh, Stephen B., Waters, Aoife, Watt, Angela, Webster, Phil, Wechalekar, Ashutosh, Welsh, Gavin Iain, West, Nicol, Wheeler, David, Wiles, Kate, Willcocks, Lisa, Williams, Angharad, Williams, Emma, Williams, Karen, Wilson, Deborah H., Wilson, Patricia D., Winyard, Paul, Wong, Edwin, Wong, Katie, Wood, Grahame, Woodward, Emma, Woodward, Len, Woolf, Adrian, Wright, David, Downward, Lewis, Griffin, Sian, Hall, Matt, Karet Frankl, Fiona, Maher, Eamonn R., Pinney, Jenny, Tam, Frederick W.K., Wilson, Patricia, Sy, Karla Therese L., Huang, Kui, Ye, Jamie, Nitsch, Dorothea, and Bockenhauer, Detlef
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- 2024
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7. Longitudinal microbial and molecular dynamics in the cystic fibrosis lung after Elexacaftor–Tezacaftor–Ivacaftor therapy
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Christian Martin, Douglas V. Guzior, Cely T. Gonzalez, Maxwell Okros, Jenna Mielke, Lienwil Padillo, Gabriel Querido, Marissa Gil, Ryan Thomas, Marc McClelland, Doug Conrad, Stefanie Widder, and Robert A. Quinn
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Cystic fibrosis ,Microbiome ,Metabolome ,Neutral models ,Elexacaftor–Tezacaftor–Ivacaftor ,Pseudomonas aeruginosa ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Cystic fibrosis (CF) is a genetic disorder causing poor mucociliary clearance in the airways and subsequent respiratory infection. The recently approved triple therapy Elexacaftor–Tezacaftor–Ivacaftor (ETI) has significantly improved lung function and decreased airway infection in persons with CF (pwCF). This improvement has been shown to occur rapidly, within the first few weeks of treatment. The effects of longer term ETI therapy on lung infection dynamics, however, remain mostly unknown. Results Here, we applied 16S rRNA gene amplicon sequencing, untargeted metabolomics, and neutral models to high-resolution, longitudinally collected sputum samples from pwCF on ETI therapy (162 samples, 7 patients) and compared to similarly collected data set from pwCF not taking ETI (630 samples, 9 patients). Because ETI reduces sputum production, samples were collected in freezers provided in the subject’s homes at least 3 months after first taking ETI, with those on ETI collecting a sample approximately weekly. The lung function (%ppFEV1) of those in our longitudinal cohort significantly improved after ETI (6.91, SD = 7.74), indicating our study cohort was responsive to ETI. The daily variation of alpha- and beta-diversity of both the microbiome and metabolome was higher for those on ETI, reflecting a more dynamic microbial community and chemical environment during treatment. Four of the seven subjects on ETI were persistently infected with Pseudomonas or Burkholderia in their sputum throughout the sampling period while the total bacterial load significantly decreased with time (R = − 0.42, p = 0.01) in only one subject. The microbiome and metabolome dynamics on ETI were personalized, where some subjects had a progressive change with time on therapy, whereas others had no association with time on treatment. To further classify the augmented variance of the CF microbiome under therapy, we fit the microbiome data to a Hubbell neutral dynamics model in a patient-stratified manner and found that the subjects on ETI had better fit to a neutral model. Conclusion This study shows that the longitudinal microbiology and chemistry in airway secretions from subjects on ETI has become more dynamic and neutral and that after the initial improvement in lung function, many are still persistently infected with CF pathogens.
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- 2023
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8. Amitriptyline inhibits bronchoconstriction and directly promotes dilatation of the airways
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Paulina Hempel, Virag Klein, Anna Michely, Svenja Böll, Annette D. Rieg, Jan Spillner, Till Braunschweig, Saskia von Stillfried, Norbert Wagner, Christian Martin, Klaus Tenbrock, and Eva Verjans
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Amitriptyline ,Bronchoconstriction ,Bronchodilation ,Inhibition ,Muscarine receptor ,PCLS ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Introduction The standard therapy for bronchial asthma consists of combinations of acute (short-acting ß2-sympathomimetics) and, depending on the severity of disease, additional long-term treatment (including inhaled glucocorticoids, long-acting ß2-sympathomimetics, anticholinergics, anti-IL-4R antibodies). The antidepressant amitriptyline has been identified as a relevant down-regulator of immunological TH2-phenotype in asthma, acting—at least partially—through inhibition of acid sphingomyelinase (ASM), an enzyme involved in sphingolipid metabolism. Here, we investigated the non-immunological role of amitriptyline on acute bronchoconstriction, a main feature of airway hyperresponsiveness in asthmatic disease. Methods After stimulation of precision cut lung slices (PCLS) from mice (wildtype and ASM-knockout), rats, guinea pigs and human lungs with mediators of bronchoconstriction (endogenous and exogenous acetylcholine, methacholine, serotonin, endothelin, histamine, thromboxane-receptor agonist U46619 and leukotriene LTD4, airway area was monitored in the absence of or with rising concentrations of amitriptyline. Airway dilatation was also investigated in rat PCLS by prior contraction induced by methacholine. As bronchodilators for maximal relaxation, we used IBMX (PDE inhibitor) and salbutamol (ß2-adrenergic agonist) and compared these effects with the impact of amitriptyline treatment. Isolated perfused lungs (IPL) of wildtype mice were treated with amitriptyline, administered via the vascular system (perfusate) or intratracheally as an inhalation. To this end, amitriptyline was nebulized via pariboy in-vivo and mice were ventilated with the flexiVent setup immediately after inhalation of amitriptyline with monitoring of lung function. Results Our results show amitriptyline to be a potential inhibitor of bronchoconstriction, induced by exogenous or endogenous (EFS) acetylcholine, serotonin and histamine, in PCLS from various species. The effects of endothelin, thromboxane and leukotrienes could not be blocked. In acute bronchoconstriction, amitriptyline seems to act ASM-independent, because ASM-deficiency (Smdp1−/−) did not change the effect of acetylcholine on airway contraction. Systemic as well as inhaled amitriptyline ameliorated the resistance of IPL after acetylcholine provocation. With the flexiVent setup, we demonstrated that the acetylcholine-induced rise in central and tissue resistance was much more marked in untreated animals than in amitriptyline-treated ones. Additionally, we provide clear evidence that amitriptyline dilatates pre-contracted airways as effectively as a combination of typical bronchodilators such as IBMX and salbutamol. Conclusion Amitriptyline is a drug of high potential, which inhibits acute bronchoconstriction and induces bronchodilatation in pre-contracted airways. It could be one of the first therapeutic agents in asthmatic disease to have powerful effects on the TH2-allergic phenotype and on acute airway hyperresponsiveness with bronchoconstriction, especially when inhaled.
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- 2023
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9. Metabolic Acidosis Is Associated With an Accelerated Decline of Allograft Function in Pediatric Kidney Transplantation
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Ariceta, Gema, Awan, Atif, Bakkaloğlu, Sevcan, Bonthuis, Marjolein, Robroeks, Charlotte Bootsma, Bouts, Antonia, Christian, Martin, Cornelissen, Marlies, Duzova, Ali, Esfandiar, Nasrin, Ghio, Luciana, Grenda, Ryszard, Guzzo, Isabella, Goni, Maria Herrero, Hogan, Julien, Hongsawong, Nattaphorn, Kanzelmeyer, Nele, Bayazit, Aysun Karabay, Aksoy, Gülşah Kaya, Knops, Noel, Kamphuis, Linda Koster, Erez, Daniella Levy, Lopez-Baez, Victor, Madrid, Alvaro, Marks, Stephen, Melk, Anette, Murer, Luisa, Pape, Lars, Peruzzi, Licia, Petrosyan, Edita, Preka, Evgenia, Printza, Nikoleta, Rachisan, Andreea Liana, Raes, Ann, Shenoy, Mohan, Soylemezoglu, Oguz, Strologo, Luca Dello, Teixeira, Ana, Topaloglu, Rezan, Weitz, Markus, Zieg, Jakub, Zlatanova, Galia, Patry, Christian, Harambat, Jerome, Ağbaş, Ayşe, Askiti, Varvara, Avramescu, Marina, Bacchetta, Justine, Bakkaloglu, Sevcan, Bontuis, Marjolein, Booth, Caroline, Dehoux, Laurene, Dizazzo, Giacomo, Drozdz, Dorota, Dursun, Ismail, Gessner, Michaela, Groothoff, Jaap, Guido, Giuliana, Klaus, Guenter, Koster-Kamphuis, Linda, Lalayiannis, Alexander, Leifheit-Nestler, Maren, Manish, Sinha, Matteucci, Chiara, Oh, Jun, Ozkaya, Ozan, Pietrement, Christine, Prytula, Agnieszka, Reusz, George, Schaefer, Franz, Schmitt, Claus Peter, Schön, Anne, Sever, Fatma Lale, Stabouli, Stella, Döven, Serra Sürmeli, Tondel, Camilla, Verrina, Enrico, Vidal, Enrico, Wallace, Dean, Arslan, Zainab, Bald, M., Fehrenbach, H., Haffner, D., Hansen, M., Hempel, C., John, U., Klaus, G., König, J., Lange-Sperandio, B., Müller, D., Oh, J., Pape, L., Pohl, M., Sauerstein, K., Schalk, G., Staude, H., Strotmann, P., Weber, L.T., Weitz, M., Berta, L., Heindl-Rusai, K., Shroff, Rukshana, van Gremberghe, Ineke, Krupka, Kai, Benetti, Elisa, Büyükkaragöz, Bahar, Kranz, Birgitta, Nalçacıoğlu, Hülya, Sellier-Leclerc, Anne-Laure, and Tönshoff, Burkhard
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- 2024
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10. Influence of ATLG serum levels on CD3/CD19-depleted hematopoietic grafts and on immune recovery in pediatric haplo-HSCT
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Maier, Claus-Philipp, Klose, Chihab, Seitz, Christian Martin, Heubach, Florian, Döring, Michaela, Meisel, Roland, Schuster, Friedhelm, Gruhn, Bernd, Keller, Frieder, Rabsteyn, Armin, Arendt, Anne-Marie, Amorelli, Germano, Eichholz, Thomas, Feuchtinger, Tobias, Martinius, Holger, Nierkens, Stefan, Teltschik, Rouwen, Schulte, Johannes Hubertus, Lengerke, Claudia, Handgretinger, Rupert, and Lang, Peter
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- 2024
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11. Single-polyp metabolomics reveals biochemical structuring of the coral holobiont at multiple scales
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Ty N. F. Roach, Shayle B. Matsuda, Christian Martin, Gintare Huckeba, Joel Huckeba, Valerie Kahkejian, Erika P. Santoro, Anneke van der Geer, Crawford Drury, and Robert A. Quinn
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Biology (General) ,QH301-705.5 - Abstract
Abstract All biology happens in space, and spatial structuring plays an important role in mediating biological processes at all scales from cells to ecosystems. However, the metabolomic structuring of the coral holobiont has yet to be fully explored. Here, we present a method to detect high-quality metabolomic data from individual coral polyps and apply this method to study the patterning of biochemicals across multiple spatial (~1 mm - ~100 m) and organizational scales (polyp to population). The data show a strong signature for individual coral colonies, a weaker signature of branches within colonies, and variation at the polyp level related to the polyps’ location along a branch. Mapping metabolites to either the coral or algal components of the holobiont reveals that polyp-level variation along the length of a branch was largely driven by molecules associated with the cnidarian host as opposed to the algal symbiont, predominantly putative sulfur-containing metabolites. This work yields insights on the spatial structuring of biochemicals in the coral holobiont, which is critical for design, analysis, and interpretation of studies on coral reef biochemistry.
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- 2023
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12. A pragmatic, open-label, randomized controlled trial of Plasma-Lyte-148 versus standard intravenous fluids in children receiving kidney transplants (PLUTO)
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Hayes, Wesley N., Laing, Emma, Brown, Rosemary, Silsby, Laura, Smith, Laura, Thomas, Helen, Kaloyirou, Fotini, Sharma, Rupa, Griffiths, James, Hume-Smith, Helen, Marks, Stephen D., Kessaris, Nicos, Christian, Martin, Dudley, Jan, Shenoy, Mohan, Malina, Michal, Muorah, Mordi, Ware, Nicholas, Yadav, Pallavi, Reynolds, Ben, Bryant, William, Spiridou, Anastassia, Wray, Jo, and Peters, Mark J.
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- 2024
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13. Using Physiological Markers to Assess Comfort during Neuromuscular Electrical Stimulation Induced Muscle Contraction in a Virtually Guided Environment: Pilot Study for a Path toward Combating ICU-Acquired Weakness
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Ahmad Abou-Hamde, Lauren Philippi, Eric Jones, Christian Martin, Kingsley Wu, Michael Kundell, Sunita Mathur, Alireza Sadeghian, Maryam Davoudpour, Jane Batt, Adriana Ieraci, and Sharon Gabison
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electric stimulation ,heart rate ,feasibility studies ,intensive care units ,Chemical technology ,TP1-1185 - Abstract
We assessed the feasibility of implementing a virtually guided Neuromuscular Electrical Stimulation (NMES) protocol over the tibialis anterior (TA) muscle while collecting heart rate (HR), Numeric Pain Rating Scale (NPRS), and quality of contraction (QoC) data. We investigated if HR, NPRS, and QoC differ ON and OFF the TA motor point and explored potential relationships between heart rate variability (HRV) and the NPRS. Twelve healthy adults participated in this cross-sectional study. Three NMES trials were delivered ON and OFF the TA motor point. HR, QoC, and NPRS data were collected. There was no significant difference in HRV ON and OFF the motor point (p > 0.05). The NPRS was significantly greater OFF the motor point (p < 0.05). The QoC was significantly different between motor point configurations (p < 0.05). There was no correlation between the NPRS and HRV (p > 0.05, r = −0.129). We recommend non-electrical methods of measuring muscle activity for future studies. The NPRS and QoC can be administered virtually. Time-domain HRV measures could increase the validity of the protocol. The variables should be explored further virtually to enhance the protocol before eventual ICU studies.
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- 2024
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14. Atypical hemolytic uremic syndrome in the era of terminal complement inhibition: an observational cohort study
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Holt, Richard, Jones, Caroline, Ashman, Neil, Fan, Stanley, Forbes, Suzanne, Rajakariar, Ravindra, De Freitas, Declan, Magee, Colm, Hanko, Jennifer, Milford, David, Muorah, Mordi, Howie, Alexander J., Baharani, Jyoti, Dasgupta, Indranil, Roberts, Russell, MacDiarmaid-Gordon, Adam, Fry, Andrew, Torpey, Nicholas, Waldron, Mary, Awan, Atif, Raftery, Tara, Ratcliffe, Laura, Vilar, Enric, Newman, Joel, Seviar, Dale, Marks, Stephen D., Rees, Lesley, Veligratli, Faidra, Waters, Aoife, Chowdhury, Paramit, Pattison, James, Booth, Caroline, Williams, Nicole, Corbett, Richard, Amin, Beena, Pickering, Matthew, Bramham, Kate, Al-Hamed, Mohamed, Hill, Anita, Mooney, Andrew, Finlay, Eric, Newnham, Amanda, Yadav, Pallavi, Kaur, Amrit, Plant, Nicholas, Shenoy, Mohan, Choong, Lye Wai, Helps, Aileen, McLemon, Robert, Muniraju, Thalakunte, Khan, Izhar, Kidder, Dana, Padmanabhan, Neal, Cousland, Zoe, Price, Jonathan, Taylor, Alison, Jennings, Claudine, Ahmad, Sohail, Mead, Paul, Aslam, Mona, Bebb, Charlotte, Byrne, Catherine, Ferraro, Alastair, Christian, Martin, Evans, Jonathan, Kim, Jon Jin, Lunn, Andrew, Mallik, Meeta, Mason, Phil, Mole, David, Craze, Janet, Sangala, Nicholas, Uniacke, Mark, McGregor, Ellon, Lambie, Stewart, Bhandary, Nitin, Flossmann, Oliver, Mohteshamzadeh, Mobin, Abeyaratne, Asanga, Bingham, Coralie, Clissold, Rhian, Smyth, Lucy, Connolly, John, Reynolds, Ben, Neary, John, Bell, Joanne, Roxburgh, Sarah, Popoola, Joyce, Donne, Rosie, Fardon, Nicholas, Khwaja, Arif, Siddiqi, Shareen, Kumar, Gurinder, Kardasz, Steve, Moore, Iain, Tez, Didem, Willows, Jamie, Davison, Rachel, Harty, John, Wong, William, Williams, Andrew J., Gale, Daniel, Coward, Richard, Inward, Carol, Mraz, Martin, Ayub, Waqar, Short, Andrew, Lappin, David, Baines, Richard, Bommayya, Girish, Houlberg, Kris, Saif, Imran, Gilbert, Rodney, Griffin, Sian, Smith, Graham, Van Der Voort, Judith, Chandar, Jayanthi, Freundlich, Michael, McCarroll, Frank, Wong, Germaine, Laboi, Paul, Molyneux, Rebekah, Brocklebank, Vicky, Walsh, Patrick R., Smith-Jackson, Kate, Hallam, Thomas M., Marchbank, Kevin J., Wilson, Valerie, Bigirumurame, Theophile, Dutt, Tina, Montgomery, Emma K., Malina, Michal, Wong, Edwin K. S., Johnson, Sally, Sheerin, Neil S., and Kavanagh, David
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- 2023
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15. Common Risk Variants in AHI1 Are Associated With Childhood Steroid Sensitive Nephrotic Syndrome
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Downie, Mallory L., Gupta, Sanjana, Voinescu, Catalin, Levine, Adam P., Sadeghi-Alavijeh, Omid, Dufek-Kamperis, Stephanie, Cao, Jingjing, Christian, Martin, Kari, Jameela A., Thalgahagoda, Shenal, Ranawaka, Randula, Abeyagunawardena, Asiri, Gbadegesin, Rasheed, Parekh, Rulan, Kleta, Robert, Bockenhauer, Detlef, Stanescu, Horia C., and Gale, Daniel P.
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- 2023
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16. Targets and Effects of Common Biocompounds of Hibiscus sabdariffa (Delphinidin-3-Sambubiosid, Quercetin, and Hibiscus Acid) in Different Pathways of Human Cells According to a Bioinformatic Assay
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Sergio R. Zúñiga-Hernández, Trinidad García-Iglesias, Monserrat Macías-Carballo, Alejandro Pérez-Larios, Yanet Karina Gutiérrez-Mercado, Gabriela Camargo-Hernández, and Christian Martin Rodríguez-Razón
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delphinidin-3-sambubiosid ,quercetin ,hibiscus acid ,bioinformatics ,Hibiscus sabdariffa ,Nutrition. Foods and food supply ,TX341-641 - Abstract
The utilization of food as a therapeutic measure for various ailments has been a prevalent practice throughout history and across different cultures. This is exemplified in societies where substances like Hibiscus sabdariffa have been employed to manage health conditions like hypertension and elevated blood glucose levels. The inherent bioactive compounds found in this plant, namely, delphinidin-3-sambubioside (DS3), quercetin (QRC), and hibiscus acid (HA), have been linked to various health benefits. Despite receiving individual attention, the specific molecular targets for these compounds remain unclear. In this study, computational analysis was conducted using bioinformatics tools such as Swiss Target Prediction, ShinnyGo 0.77, KEGG, and Stringdb to identify the molecular targets, pathways, and hub genes. Supplementary results were obtained through a thorough literature search in PubMed. DS3 analysis revealed potential genetic alterations related to the metabolism of nitrogen and glucose, inflammation, angiogenesis, and cell proliferation, particularly impacting the PI3K-AKT signaling pathway. QRC analysis demonstrated interconnected targets spanning multiple pathways, with some overlap with DS3 analysis and a particular focus on pathways related to cancer. HA analysis revealed distinct targets, especially those associated with pathways related to the nervous system. These findings emphasize the necessity for focused research on the molecular effects of DS3, QRC, and HA, thereby providing valuable insights into potential therapeutic pathways.
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- 2024
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17. Case report: A novel SON mutation in a Colombian patient with ZTTK syndrome
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Diana Marcela Vasquez-Forero, Barbara Masotto, Rosario Ferrer-Avargues, Christian Martin Moya, and Harry Pachajoa
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SON ,Zhu–Tokita–Takenouchi–Kim syndrome ,ZTTK syndrome ,rare disease ,Colombia ,Genetics ,QH426-470 - Abstract
Zhu–Tokita–Takenouchi–Kim syndrome is a multisystem disorder resulting from haploinsufficiency in the SON gene, which is characterized by developmental delay/intellectual disability, seizures, facial dysmorphism, short stature, and congenital malformations, primarily in the central nervous system, along with ophthalmic, dental, pulmonary, cardiologic, renal, gastrointestinal, and musculoskeletal anomalies. In this study, we describe the first Colombian patient with ZTT harboring a novel mutation that has not been previously reported and review the clinical and molecular features of previously reported patients in the literature.
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- 2023
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18. Hyperparathyroidism Is an Independent Risk Factor for Allograft Dysfunction in Pediatric Kidney Transplantation
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Prytula, Agnieszka, Shroff, Rukshana, Krupka, Kai, Deschepper, Ellen, Bacchetta, Justine, Ariceta, Gema, Awan, Atif, Benetti, Elisa, Büscher, Anja, Berta, László, Carraro, Andrea, Christian, Martin, Dello Strologo, Luca, Doerry, Katja, Haumann, Sophie, Klaus, Guenter, Kempf, Caroline, Kranz, Birgitta, Oh, Jun, Pape, Lars, Pohl, Martin, Printza, Nikoleta, Rubik, Jacek, Schmitt, Claus Peter, Shenoy, Mohan, Spartà, Giuseppina, Staude, Hagen, Sweeney, Clodagh, Weber, Lutz, Weber, Stefanie, Weitz, Marcus, Haffner, Dieter, and Tönshoff, Burkhard
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- 2023
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19. Complex and unexpected outcomes of antibiotic therapy against a polymicrobial infection
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Ghuneim, Lydia-Ann J., Raghuvanshi, Ruma, Neugebauer, Kerri A., Guzior, Douglas V., Christian, Martin H., Schena, Bella, Feiner, Jeremiah M., Castillo-Bahena, Alicia, Mielke, Jenna, McClelland, Marc, Conrad, Douglas, Klapper, Isaac, Zhang, Tianyu, and Quinn, Robert A.
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- 2022
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20. Economic Evaluation of Using Daily Prednisolone versus Placebo at the Time of an Upper Respiratory Tract Infection for the Management of Children with Steroid-Sensitive Nephrotic Syndrome: A Model-Based Analysis
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Afentou, Nafsika, Frew, Emma, Mehta, Samir, Ives, Natalie J., Woolley, Rebecca L., Brettell, Elizabeth A., Khan, Adam R., Milford, David V., Bockenhauer, Detlef, Saleem, Moin A., Hall, Angela S., Koziell, Ania, Maxwell, Heather, Hegde, Shivaram, Finlay, Eric, Gilbert, Rodney D., Jones, Caroline, McKeever, Karl, Cook, Wendy, Webb, Nicholas J. A., and Christian, Martin T.
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- 2022
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21. Functional changes in long-term incubated rat precision-cut lung slices
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Sarah Marie Nußbaum, Julia Krabbe, Svenja Böll, Aaron Babendreyer, and Christian Martin
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Precision-cut lung slices ,PCLS ,Rat ,Long-term incubation ,Viability ,Histopathology ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Respiratory diseases represent a global health burden. Because research on therapeutic strategies of airway diseases is essential, the technique of precision-cut lung slices (PCLS) has been developed and widely studied. PCLS are an alternative ex vivo model and have the potential to replace and reduce in vivo animal models. So far, the majority of studies was conducted with short-term cultivated PCLS (≤ 72 h). As there is large interest in research of chronic diseases and chronic toxicity, feasibility of cultivating human PCLS long-term over 2 weeks and recently over 4 weeks was investigated by another research group with successful results. Our aim was to establish a model of long-term cultivated rat PCLS over a period of 29 days. Methods Rat PCLS were cultured for 29 days and analysed regarding viability, histopathology, reactivity and gene expression at different time points during cultivation. Results Cultivation of rat PCLS over a 29-day time period was successful with sustained viability. Furthermore, the ability of bronchoconstriction was maintained between 13 and 25 days, depending on the mediator. However, reduced relaxation, altered sensitivity and increased respiratory tone were observed. Regarding transcription, alteration in gene expression pattern of the investigated target genes was ascertained during long-term cultivation with mixed results. Furthermore, the preparation of PCLS seems to influence messenger ribonucleic acid (mRNA) expression of most target genes. Moreover, the addition of fetal bovine serum (FBS) to the culture medium did not improve viability of PCLS. In contrast to medium without FBS, FBS seems to affect measurements and resulted in marked cellular changes of metaplastic and/or regenerative origin. Conclusions Overall, a model of long-term cultivated rat PCLS which stays viable for 29 days and reactive for at least 13 days could be established. Before long-term cultivated PCLS can be used for in-depth study of chronic diseases and chronic toxicity, further investigations have to be made.
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- 2022
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22. Platelet-derived growth factor (PDGF)-BB regulates the airway tone via activation of MAP2K, thromboxane, actin polymerisation and Ca2+-sensitisation
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Annette D. Rieg, Said Suleiman, Carolin Anker, Nina A. Bünting, Eva Verjans, Jan Spillner, Sebastian Kalverkamp, Saskia von Stillfried, Till Braunschweig, Stefan Uhlig, and Christian Martin
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Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background PDGFR-inhibition by the tyrosine kinase inhibitor (TKI) nintedanib attenuates the progress of idiopathic pulmonary fibrosis (IPF). However, the effects of PDGF-BB on the airway tone are almost unknown. We studied this issue and the mechanisms beyond, using isolated perfused lungs (IPL) of guinea pigs (GPs) and precision-cut lung slices (PCLS) of GPs and humans. Methods IPL: PDGF-BB was perfused after or without pre-treatment with the TKI imatinib (perfused/nebulised) and its effects on the tidal volume (TV), the dynamic compliance (Cdyn) and the resistance were studied. PCLS (GP): The bronchoconstrictive effects of PDGF-BB and the mechanisms beyond were evaluated. PCLS (human): The bronchoconstrictive effects of PDGF-BB and the bronchorelaxant effects of imatinib were studied. All changes of the airway tone were measured by videomicroscopy and indicated as changes of the initial airway area. Results PCLS (GP/human): PDGF-BB lead to a contraction of airways. IPL: PDGF-BB decreased TV and Cdyn, whereas the resistance did not increase significantly. In both models, inhibition of PDGFR-(β) (imatinib/SU6668) prevented the bronchoconstrictive effect of PDGF-BB. The mechanisms beyond PDGF-BB-induced bronchoconstriction include activation of MAP2K and TP-receptors, actin polymerisation and Ca2+-sensitisation, whereas the increase of Ca2+ itself and the activation of EP1–4-receptors were not of relevance. In addition, imatinib relaxed pre-constricted human airways. Conclusions PDGFR regulates the airway tone. In PCLS from GPs, this regulatory mechanism depends on the β-subunit. Hence, PDGFR-inhibition may not only represent a target to improve chronic airway disease such as IPF, but may also provide acute bronchodilation in asthma. Since asthma therapy uses topical application. This is even more relevant, as nebulisation of imatinib also appears to be effective.
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- 2022
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23. Description and cross-sectional analyses of 25,880 adults and children in the UK National Registry of Rare Kidney Diseases cohort
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Wong, Katie, primary, Pitcher, David, additional, Braddon, Fiona, additional, Downward, Lewis, additional, Steenkamp, Retha, additional, Masoud, Sherry, additional, Annear, Nicholas, additional, Barratt, Jonathan, additional, Bingham, Coralie, additional, Coward, Richard J., additional, Chrysochou, Tina, additional, Game, David, additional, Griffin, Sian, additional, Hall, Matt, additional, Johnson, Sally, additional, Kanigicherla, Durga, additional, Karet Frankl, Fiona, additional, Kavanagh, David, additional, Kerecuk, Larissa, additional, Maher, Eamonn R., additional, Moochhala, Shabbir, additional, Pinney, Jenny, additional, Sayer, John A., additional, Simms, Roslyn, additional, Sinha, Smeeta, additional, Srivastava, Shalabh, additional, Tam, Frederick W.K., additional, Thomas, Kay, additional, Turner, A. Neil, additional, Walsh, Stephen B., additional, Waters, Aoife, additional, Wilson, Patricia, additional, Wong, Edwin, additional, Abat, Sharirose, additional, Adalat, Shazia, additional, Agbonmwandolor, Joy, additional, Ahmad, Zubaidah, additional, Alejmi, Abdulfattah, additional, Almasarwah, Rashid, additional, Asgari, Ellie, additional, Ayers, Amanda, additional, Baharani, Jyoti, additional, Balasubramaniam, Gowrie, additional, Jo-Bamba Kpodo, Felix, additional, Bansal, Tarun, additional, Barratt, Alison, additional, Bates, Megan, additional, Bayne, Natalie, additional, Bendle, Janet, additional, Benyon, Sarah, additional, Bergmann, Carsten, additional, Bhandari, Sunil, additional, Boddana, Preetham, additional, Bond, Sally, additional, Bramham, Kate, additional, Branson, Angela, additional, Brearey, Stephen, additional, Brocklebank, Vicky, additional, Budwal, Sharanjit, additional, Byrne, Conor, additional, Cairns, Hugh, additional, Camilleri, Brian, additional, Campbell, Gary, additional, Capell, Alys, additional, Carmody, Margaret, additional, Carson, Marion, additional, Cathcart, Tracy, additional, Catley, Christine, additional, Cesar, Karine, additional, Chan, Melanie, additional, Chea, Houda, additional, Chess, James, additional, Cheung, Chee Kay, additional, Chick, Katy-Jane, additional, Chitalia, Nihil, additional, Christian, Martin, additional, Clark, Katherine, additional, Clayton, Christopher, additional, Clissold, Rhian, additional, Cockerill, Helen, additional, Coelho, Joshua, additional, Colby, Elizabeth, additional, Colclough, Viv, additional, Conway, Eileen, additional, Cook, H. Terence, additional, Cook, Wendy, additional, Cooper, Theresa, additional, Crosbie, Sarah, additional, Cserep, Gabor, additional, Date, Anjali, additional, Davidson, Katherine, additional, Davies, Amanda, additional, Dhaun, Neeraj, additional, Dhaygude, Ajay, additional, Diskin, Lynn, additional, Dixit, Abhijit, additional, Doctolero, Eunice Ann, additional, Dorey, Suzannah, additional, Downard, Lewis, additional, Drayson, Mark, additional, Dreyer, Gavin, additional, Dutt, Tina, additional, Etuk, Kufreabasi, additional, Evans, Dawn, additional, Finch, Jenny, additional, Flinter, Frances, additional, Fotheringham, James, additional, Francis, Lucy, additional, Gale, Daniel P., additional, Gallagher, Hugh, additional, Garcia, Eva Lozano, additional, Gavrila, Madita, additional, Gear, Susie, additional, Geddes, Colin, additional, Gilchrist, Mark, additional, Gittus, Matt, additional, Goggolidou, Paraskevi, additional, Goldsmith, Christopher, additional, Gooden, Patricia, additional, Goodlife, Andrea, additional, Goodwin, Priyanka, additional, Grammatikopoulos, Tassos, additional, Gray, Barry, additional, Griffith, Megan, additional, Gumus, Steph, additional, Gupta, Sanjana, additional, Hamilton, Patrick, additional, Harper, Lorraine, additional, Harris, Tess, additional, Haskell, Louise, additional, Hayward, Samantha, additional, Hegde, Shivaram, additional, Hendry, Bruce, additional, Hewins, Sue, additional, Hewitson, Nicola, additional, Hillman, Kate, additional, Hiremath, Mrityunjay, additional, Howson, Alexandra, additional, Htet, Zay, additional, Huish, Sharon, additional, Hull, Richard, additional, Humphries, Alister, additional, Hunt, David P.J., additional, Hunter, Karl, additional, Hunter, Samantha, additional, Ijeomah-Orji, Marilyn, additional, Inston, Nick, additional, Jayne, David, additional, Jenfa, Gbemisola, additional, Jenkins, Alison, additional, Jones, Caroline A., additional, Jones, Colin, additional, Jones, Amanda, additional, Jones, Rachel, additional, Kamesh, Lavanya, additional, Frankl, Fiona Karet, additional, Karim, Mahzuz, additional, Kaur, Amrit, additional, Kearley, Kelly, additional, Khwaja, Arif, additional, King, Garry, additional, King, Grant, additional, Kislowska, Ewa, additional, Klata, Edyta, additional, Kokocinska, Maria, additional, Lambie, Mark, additional, Lawless, Laura, additional, Ledson, Thomas, additional, Lennon, Rachel, additional, Levine, Adam P., additional, Maggie Lai, Ling Wai, additional, Lipkin, Graham, additional, Lovitt, Graham, additional, Lyons, Paul, additional, Mabillard, Holly, additional, Mackintosh, Katherine, additional, Mahdi, Khalid, additional, Maher, Eamonn, additional, Marchbank, Kevin J., additional, Mark, Patrick B., additional, Masunda, Bridgett, additional, Mavani, Zainab, additional, Mayfair, Jake, additional, McAdoo, Stephen, additional, Mckinnell, Joanna, additional, Melhem, Nabil, additional, Meyrick, Simon, additional, Morgan, Putnam, additional, Morgan, Ann, additional, Muhammad, Fawad, additional, Murray, Shona, additional, Novobritskaya, Kristina, additional, Ong, Albert CM., additional, Oni, Louise, additional, Osmaston, Kate, additional, Padmanabhan, Neal, additional, Parkes, Sharon, additional, Patrick, Jean, additional, Pattison, James, additional, Paul, Riny, additional, Percival, Rachel, additional, Perkins, Stephen J., additional, Persu, Alexandre, additional, Petchey, William G., additional, Pickering, Matthew C., additional, Pinney, Jennifer, additional, Plumb, Lucy, additional, Plummer, Zoe, additional, Popoola, Joyce, additional, Post, Frank, additional, Power, Albert, additional, Pratt, Guy, additional, Pusey, Charles, additional, Rabara, Ria, additional, Rabuya, May, additional, Raju, Tina, additional, Javier, Chadd, additional, Roberts, Ian SD., additional, Roufosse, Candice, additional, Rumjon, Adam, additional, Salama, Alan, additional, Saleem, Moin, additional, Sandford, R.N., additional, Sandu, Kanwaljit S., additional, Sarween, Nadia, additional, Sebire, Neil, additional, Selvaskandan, Haresh, additional, Shah, Sapna, additional, Sharma, Asheesh, additional, Sharples, Edward J., additional, Sheerin, Neil, additional, Shetty, Harish, additional, Shroff, Rukshana, additional, Sinha, Manish, additional, Smith, Kerry, additional, Smith, Lara, additional, Stott, Ian, additional, Stroud, Katerina, additional, Swift, Pauline, additional, Szklarzewicz, Justyna, additional, Tam, Fred, additional, Tan, Kay, additional, Taylor, Robert, additional, Tischkowitz, Marc, additional, Tse, Yincent, additional, Turnbull, Alison, additional, Turner, A Neil, additional, Tyerman, Kay, additional, Usher, Miranda, additional, Venkat-Raman, Gopalakrishnan, additional, Walker, Alycon, additional, Watt, Angela, additional, Webster, Phil, additional, Wechalekar, Ashutosh, additional, Welsh, Gavin Iain, additional, West, Nicol, additional, Wheeler, David, additional, Wiles, Kate, additional, Willcocks, Lisa, additional, Williams, Angharad, additional, Williams, Emma, additional, Williams, Karen, additional, Wilson, Deborah H., additional, Wilson, Patricia D., additional, Winyard, Paul, additional, Wong, Katie, additional, Wood, Grahame, additional, Woodward, Emma, additional, Woodward, Len, additional, Woolf, Adrian, additional, Wright, David, additional, Sy, Karla Therese L., additional, Huang, Kui, additional, Ye, Jamie, additional, Nitsch, Dorothea, additional, and Bockenhauer, Detlef, additional
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- 2024
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24. Age‐based centiles for diastolic blood pressure among children in the out‐of‐hospital emergency setting
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Sriram Ramgopal, Robert J Sepanski, Remle P Crowe, and Christian Martin‐Gill
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blood pressure ,child ,emergency medical services ,emergency medicine ,hypertension ,hypotension ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Objective To compare Pediatric Advanced Life Support (PALS) diastolic blood pressure (DBP) criteria to empirically derived DBP criteria for the prediction of out‐of‐hospital interventions in children. Methods We performed a retrospective study of pediatric (90th centile). The accuracy of low DBP for out‐of‐hospital interventions between the two criteria was similar. Conclusion PALS criteria for DBP classified a high proportion of children as having abnormal vital signs, particularly with diastolic hypertension. Empirically derived DBP thresholds more accurately predict the delivery of key out‐of‐hospital interventions. If externally validated, correlated to in‐hospital outcomes, and combined with thresholds for other vital signs, these may better predict the need for out‐of‐hospital interventions.
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- 2023
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25. Effects of Delphinidin-3-Sambubiosid on Different Pathways of Human Cells According to a Bioinformatic Analysis
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Sergio R. Zúñiga-Hernández, Trinidad García-Iglesias, Monserrat Macías-Carballo, Alejandro Perez-Larios, and Christian Martin Rodríguez-Razón
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hibiscus sabdariffa ,delphinidin-3-sambubiosid ,bioinformatics ,Plant ecology ,QK900-989 ,Animal biochemistry ,QP501-801 ,Biology (General) ,QH301-705.5 - Abstract
The use of food and its nutrients as a remedy for diseases is historically and culturally well rooted in plenty of societies. An example of this is the use of Hibiscus sabdariffa to treat conditions like hypertension or high blood glucose. Furthermore, the natural biocompounds present in this plant have been demonstrated by several authors to be hypotensive, antioxidant, anticarcinogenic, antiobesogenic, etc. One of these compounds is Delphinidin-3-Sambubiosid (DS3), the most representative anthocyanin of Hibiscus sabdariffa, and as such, it has been proposed to have the beneficial effects previously mentioned. However, little is known about the molecular targets of DS3. Therefore, we conducted an in silico analysis using different bioinformatic tools to determine the possible molecular targets of this molecule and the potential impact the modification of its targets could have on the proteins and/or pathways of humans. We used the Swiss Target Prediction site to identify all the molecular targets of DS3, and then ShinnyGo 0.77, KEGG, and Stringdb were used to identify key pathways and hub genes related to them. Also, a literature search was conducted in PubMed, where each of the hub genes was linked to DS3 so we could gather information that complemented the results of the bioinformatic tools. The results show that DS3 can modify the behavior of genes related to nitrogen and glucose metabolism, inflammation, angiogenesis, and cell proliferation. Additionally, DS3 has direct effects on the PI3K-AKT pathway, which could be a key finding promoting further research, especially to determine the implications associated with changes in the aforementioned pathway.
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- 2023
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26. The Clinical Relevance of the NATALEE Study: Application of the NATALEE Criteria to a Real-World Cohort from Two Large German Breast Cancer Centers
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Henning Schäffler, Franziska Mergel, Kerstin Pfister, Stephan Lukac, Angelina Fink, Kristina Veselinovic, Brigitte Rack, Visnja Fink, Elena Leinert, Moritz Dimpfl, Alexander Englisch, Christian Martin Tegeler, Anna Seller, Eva-Maria Grischke, Markus Hahn, Léa Louise Volmer, Tobias Engler, Marie Louise Frevert, Florin Andrei Taran, Wolfgang Janni, Sara Yvonne Brucker, Andreas Daniel Hartkopf, and Dominik Dannehl
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oncology ,breast cancer ,systemic therapy ,CDK4/6 Inhibitors ,Ribociclib ,NATALEE ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The NATALEE study showed a significant benefit in invasive disease-free survival (iDFS) for patients with HR+/HER2− early breast cancer (eBC) at intermediate and high risk of recurrence who were treated with the CDK4/6 inhibitor Ribociclib in combination with endocrine therapy (ET). This retrospective study aims to apply the NATALEE inclusion criteria to a representative real-world cohort to estimate the proportion of HR+/HER2− breast cancer patients eligible for adjuvant Ribociclib therapy. Patients who underwent full surgical treatment for eBC between January 2018 and December 2020 at two large German university breast cancer centers (University of Ulm, University of Tuebingen) were included. Descriptive statistics were used to characterize the patient population eligible for Ribociclib treatment based on the NATALEE study’s inclusion criteria. Out of 2384 enrolled patients, 1738 had HR+/HER2− eBC, of whom 43% (747/1738) met the NATALEE inclusion criteria. Of note, these patients were older, received less chemotherapy and presented with less advanced tumor stages compared to the NATALEE study cohort. Additionally, compared to the NATALEE study cohort, fewer patients had lymph node involvement (72.4% vs. 88.7%). Our analysis suggests that approximately 43% of all HR+/HER2− breast cancer patients will qualify for Ribociclib treatment. Given the numerous treatment options for patients with HR+/HER2− eBC, as well as the differences between the NATALEE cohort and patients in the real-world clinical setting, future analyses will be needed to determine which patients would benefit most from adjuvant CDK4/6 inhibitor treatment.
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- 2023
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27. Overview of DC/DC Converters for Concentrating Photovoltaics (CPVs)
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Philippe Camail, Bruno Allard, Maxime Darnon, Charles Joubert, Christian Martin, and João Pedro F. Trovão
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CPV ,DC/DC converters ,partial power processing ,PV ,granularities ,Technology - Abstract
With energy efficiencies close to two times higher than traditional photovoltaic (PV), concentrated photovoltaic (CPV) systems represent a promising solution for solar power generation. In the same way, the converging Levelized Cost of Energy (LCOE) of both technologies favors interest toward CPV systems. In order to assess more clearly the potential of this technology, an up-to-date evaluation of the power electronic conversion techniques used in CPV to increase the yielded energy is crucial. This assessment not only sheds light on the latest advancements, but also provides insights into design trade-offs, performance limitations, and potential areas for improvement in CPV systems. This work focuses on the DC/DC converters used as an intermediary stage of conversion between the panels and a central grid-tied inverter. Electrical and economical metrics are used to compare actual converters developed and presented in a comprehensive literature review.
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- 2023
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28. Intrapopulation adaptive variance supports thermal tolerance in a reef-building coral
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Crawford Drury, Nina K. Bean, Casey I. Harris, Joshua R. Hancock, Joel Huckeba, Christian Martin H, Ty N. F. Roach, Robert A. Quinn, and Ruth D. Gates
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Biology (General) ,QH301-705.5 - Abstract
Selective breeding of corals with different bleaching phenotypes demonstrates the potential for climate adaptation in vertically transmitting species.
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- 2022
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29. Intrapopulation adaptive variance supports thermal tolerance in a reef-building coral
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Drury, Crawford, Bean, Nina K., Harris, Casey I., Hancock, Joshua R., Huckeba, Joel, H, Christian Martin, Roach, Ty N. F., Quinn, Robert A., and Gates, Ruth D.
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- 2022
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30. From social networks to knowledge graphs: A plea for interdisciplinary approaches
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Dörpinghaus, Jens, Klante, Sonja, Christian, Martin, Meigen, Christof, and Düing, Carsten
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- 2022
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31. Which Patients Do We Need to Test for BRCA1/2 Mutation? Feasibility of Adjuvant Olaparib Treatment in Early Breast Cancer–Real-World Data from Two Large German Breast Centers
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Dominik Dannehl, Tobias Engler, Léa Louise Volmer, Christian Martin Tegeler, Julia Fusshoeller, Emma Gabrysch, Kenneth Eissler, Anna Seller, Eva-Maria Grischke, Markus Hahn, Ines Gruber, Fabienne Schochter, Kerstin Pfister, Kristina Veselinovic, Elena Leinert, Brigitte Rack, Visnja Fink, Wolfgang Janni, Sara Yvonne Brucker, Andreas Daniel Hartkopf, and Henning Schäffler
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breast cancer ,BRCA ,olaparib ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Approximately 6% of women with breast cancer carry pathogenic germline variants in predisposition genes such as BRCA1 and BRCA2. Depending on personal and family cancer history, it is therefore recommended to test for hereditary breast cancer. Moreover, as shown by the phase III OlympiA trial, olaparib significantly improves overall survival in patients with HER2 negative (HER2−) early breast cancer who (1) carry a BRCA1 or BRCA2 germline mutation (gBRCA1/2-positive), (2) have received (neo)adjuvant chemotherapy and (3) are at high clinical risk. The objective of the current analysis was to determine the number of patients with early HER2− breast cancer who are at high clinical risk, according to the inclusion criteria of OlympiA, and to estimate how many of these patients would meet the criteria for hereditary cancer testing in a real-world analysis. Methods: All patients included in this retrospective analysis were treated for early breast cancer (eBC) at the Department of Gynecology and Obstetrics, Ulm University Hospital, Germany, and the Department of Women’s Health at Tuebingen University Hospital, Germany, between January 2018 and December 2020. Patients were identified as high risk, in line with the clinicopathological determiners used in the OlympiA trial. The criteria of the German Consortium for Hereditary Breast and Ovarian Cancer were used to identify patients who qualify for hereditary cancer testing. Results: Of 2384 eligible patients, 1738 patients (72.9%) showed a hormone receptor positive (HR+)/HER2− tumor biology, 345 patients (14.5%) displayed HER2+ breast cancer and 301 patients (12.6%) suffered from HR-/HER2− breast cancer (TNBC). Of 2039 HER2− breast cancer patients, 271 patients (13.3%) were at high clinical risk. This cohort encompassed 130 of the 1738 patients with HR+/HER2− breast cancer (7.5%) and 141 of 301 patients with TNBC (46.8%). A total of 121 of 271 patients (44.6%) with high clinical risk met the criteria for hereditary cancer testing (34 of 130 (26.2%) HR+/HER2− patients and 87 of 141 (61.7%) patients with TNBC). Conclusion: Approximately one in ten patients with HR+/HER2−, and half of the patients with TNBC, meet the high-risk criteria according to OlympiA. Half of these patients do not meet the criteria for hereditary cancer testing and should therefore be tested for the presence of gBRCA1/2 mutations, irrespective of their own or family cancer history. The overall number of patients with early breast cancer benefiting from olaparib needs to be investigated in future studies.
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- 2023
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32. Management of patients with pulmonary mycobacteriosis in France: a multicenter retrospective cohort study
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Pascale Bemer, Olivia Peuchant, Hélène Guet-Revillet, Julien Bador, Charlotte Balavoine, Damien Basille, Guillaume Beltramo, François-Xavier Blanc, Elodie Blanchard, Sarah Boulanger, Anne Bourgoin, David Boutoille, Emmanuelle Cambau, Frédérique Canis, Didier Caparros, Anne Carricajo, Christian Carrière, Gérard Couetdic, Francis Couturaud, Jean-Charles Dalphin, Tristan Degot, Marion Desquiens, Gilles Devouassoux, Jean-Marie Duez, Oana Dumitrescu, Magali Dupuy-Grasset, Alice Gaudart, Marjolaine Georges, Cendrine Godet, Sylvain Godreuil, Aurélie Guillouzouic, Farida Hamdad-Daoudi, Geneviève Héry-Arnaud, Christelle Koebel, Aurore Lagrange, Philippe Lanotte, Sylvain Marchand-Adam, Faïza Mougari, Marlène Murris, Isabelle Patry, Michèle Pérouse de Montclos, Laurent Raskine, Karine Risso, Christine Segonds, Dominique Sicard, Dominique Terru, Anne Vachée, Jean-Michel Vergnon, Christian Martin, Frédéric Schramm, and Claire Andrejak
- Subjects
Nontuberculous mycobacteria ,Mycobacterium xenopi ,Mycobacterium avium complex ,Prognosis ,Management ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Recent studies report very low adherence of practitioners to ATS/IDSA recommendations for the treatment of nontuberculous mycobacteria pulmonary disease (NTM-PD), as well as a great variability of practices. Type of management could impact prognosis. Methods To evaluate management and prognosis of patients with NTM-PD cases with respect to ATS recommendations, we conducted a multicenter retrospective cohort study (18 sentinel sites distributed throughout France), over a period of six years. We collected clinical, radiological, microbiological characteristics, management and outcome of the patients (especially death or not). Results 477 patients with NTM-PD were included. Respiratory comorbidities were found in 68% of cases, tuberculosis sequelae in 31.4% of patients, and immunosuppression in 16.8% of cases. The three most common NTM species were Mycobacterium avium complex (60%), M. xenopi (20%) and M. kansasii (5.7%). Smear-positive was found in one third of NTM-PD. Nodulobronchiectatic forms were observed in 54.3% of cases, and cavitary forms in 19.1% of patients. Sixty-three percent of patients were treated, 72.4% of patients with smear-positive samples, and 57.5% of patients with smear-negative samples. Treatment was in adequacy with ATS guidelines in 73.5%. The 2-year mortality was 14.4%. In the Cox regression, treatment (HR = 0.51), age (HR = 1.02), and M. abscessus (3.19) appeared as the 3 significant independent prognostic factors. Conclusion These findings highlight the adequacy between French practices and the ATS/IDSA guidelines. Treatment was associated with a better survival.
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- 2021
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33. How Often Do You Think About Your Relationship With Nature? The Measurement of Environmental Identity Salience and Its Relationship With Proenvironmental Behaviors
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Leïla Rahmani, Simona Haasova, Sandor Czellar, Valentina Clergue, and Christian Martin
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proenvironmental behaviors ,environmental identity ,identity strength ,identity salience ,sustainable consumption ,measurement development ,Psychology ,BF1-990 - Abstract
Extant research finds that environmental identity is an important motivational factor for proenvironmental behavior. However, studies typically focus on investigating the effects of the strength of this identity. Based on insights from identity research, we theorize that the influence of individuals’ environmental identity on their proenvironmental behavior may depend on other identity dimensions as well. We argue that the frequency of activation of environmental identity in relevant life domains—environmental identity salience—may predict proenvironmental behavior beyond what environmental identity strength can explain. To test our theorizing, we propose a parsimonious measure of environmental identity salience. In four empirical studies, we establish that the new measure has sound psychometric properties in terms of internal consistency and discriminant validity with regard to measures of environmental identity strength. Importantly, our measure of environmental identity salience reliably predicts a range of self-reported and actual proenvironmental behaviors beyond the effects of environmental identity strength. In line with theoretical predictions, our data suggests that environmental identity salience and strength are related but distinct constructs. We conclude that investigating the nature and effects of environmental identity salience leads to a fruitful path to a more comprehensive understanding of proenvironmental behavior. The proposed new measure may serve as a helpful tool in this endeavor.
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- 2022
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34. Genetic Diversity and Population Structure of Mycobacterium bovis at the Human-Animal-Ecosystem Interface in France: 'A One Health Approach'
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Anaïs Appegren, Maria Laura Boschiroli, Krystel De Cruz, Lorraine Michelet, Geneviève Héry-Arnaud, Marie Kempf, Philippe Lanotte, Pascale Bemer, Olivia Peuchant, Martine Pestel-Caron, Soumaya Skalli, Lucien Brasme, Christian Martin, Cecilia Enault, Anne Carricajo, Hélène Guet-Revillet, Michaël Ponsoda, Véronique Jacomo, Anne Bourgoin, Sabine Trombert-Paolantoni, Christian Carrière, Chloé Dupont, Guilhem Conquet, Lokman Galal, Anne-Laure Banuls, and Sylvain Godreuil
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bovine tuberculosis ,population genetics ,zoonosis ,One Health ,France ,Medicine - Abstract
Mycobacterium bovis infects cattle and wildlife, and also causes a small proportion of tuberculosis cases in humans. In most European countries, M. bovis infections in cattle have been drastically reduced, but not eradicated. Here, to determine the M. bovis circulation within and between the human, cattle, and wildlife compartments, we characterized by spoligotyping and mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing the genetic diversity of M. bovis isolates collected from humans, cattle, and wildlife in France from 2000 to 2010. We also assessed their genetic structure within and among the different host groups, and across time and space. The M. bovis genetic structure and its spatiotemporal variations showed different dynamics in the human and animal compartments. Most genotypes detected in human isolates were absent in cattle and wildlife isolates, possibly because in patients, M. bovis infection was contracted abroad or was the reactivation of an old lesion. Therefore, they did not match the genetic pool present in France during the study period. However, some human-cattle exchanges occurred because some genotypes were common to both compartments. This study provides new elements for understanding M. bovis epidemiology in France, and calls for increased efforts to control this pathogen worldwide.
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- 2023
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35. Visible light and temperature dual-responsive microgels by crosslinking of spiropyran modified prepolymers
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Hu, Chaolei, Xu, Wenjing, Conrads, Christian Martin, Wu, Jingnan, and Pich, Andrij
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- 2021
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36. Three-year outcomes from the CRADLE study in de novo pediatric kidney transplant recipients receiving everolimus with reduced tacrolimus and early steroid withdrawal
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Tönshoff, Burkhard, Tedesco-Silva, Helio, Ettenger, Robert, Christian, Martin, Bjerre, Anna, Dello Strologo, Luca, Marks, Stephen D., Pape, Lars, Veldandi, Udaykiran, Lopez, Patricia, Cousin, Marc, Pandey, Priti, and Meier, Matthias
- Published
- 2021
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37. Masking by health care and public safety workers in non‐patient care areas to mitigate SARS‐CoV‐2 infection: A systematic review
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P. Daniel Patterson, Quentin S. Mcilvaine, Lily Nong, Mary K. Liszka, Rebekah S. Miller, Francis X. Guyette, and Christian Martin‐Gill
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COVID ,health care ,masks ,public safety ,SARS‐CoV‐2 ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Objectives Wearing a mask is an important method for reducing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission in health care and public safety settings. We assess the evidence regarding masking in the workplace during the initial months of the COVID‐19 pandemic (PROSPERO CRD4202432097). Methods We performed a systematic review of published literature from 4 databases and evaluated the quality of evidence with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. We searched for observational and experimental research involving public safety and health care workers. We included articles evaluating the use of masks, versus no mask, on the outcome of SARS‐CoV‐2 infection. Results Our search yielded 15,013 records, of which 9 studies were included. Most studies (n = 8; 88.9%) involved infections or outbreaks among health care workers. The majority (88.9%) used in‐depth interviews of cases and non‐cases to obtain self‐reported use of masks during periods of exposure. One of 9 studies quantitatively assessed differences in SARS‐CoV‐2 infection based on use of masks in non‐patient care settings. Use of observational study designs, small sample sizes, inadequate control for confounding, and inadequate measurement of exposure and non‐exposure periods with infected coworkers contributed to the quality of evidence being judged as very low. Conclusions The available evidence from the initial months of the pandemic suggests that the use of masks in congregate, non‐patient care settings, such as breakrooms, helps to reduce risk of SARS‐CoV‐2 virus transmission. However, this evidence is limited and is of very low quality. Prospective studies incorporating active observation measures are warranted.
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- 2022
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38. Napping on the night shift and its impact on blood pressure and heart rate variability among emergency medical services workers: study protocol for a randomized crossover trial
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P. Daniel Patterson, Leonard S. Weiss, Matthew D. Weaver, David D. Salcido, Samantha E. Opitz, Tiffany S. Okerman, Tanner T. Smida, Sarah E. Martin, Francis X. Guyette, Christian Martin-Gill, and Clifton W. Callaway
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Crossover trial ,Napping ,Shift work ,Medicine (General) ,R5-920 - Abstract
Abstract Background There is an emerging body of evidence that links exposure to shift work to cardiovascular disease (CVD). The risk of coronary events, such as myocardial infarction, is greater among night shift workers compared to day workers. There is reason to believe that repeated exposure to shift work, especially night shift work, creates alterations in normal circadian patterns of blood pressure (BP) and heart rate variability (HRV) and that these alterations contribute to increased risk of CVD. Recent data suggest that allowing shift workers to nap during night shifts may help to normalize BP and HRV patterns and, over time, reduce the risk of CVD. The risk of CVD related to shift work is elevated for emergency medical services (EMS) shift workers due in part to long-duration shifts, frequent use of night shifts, and a high prevalence of multiple jobs. Methods We will use a randomized crossover trial study design with three study conditions. The targeted population is comprised of EMS clinician shift workers, and our goal enrollment is 35 total participants with an estimated 10 of the 35 enrolled not completing the study protocol or classified as lost to attrition. All three conditions will involve continuous monitoring over 72 h and will begin with a 36-h at-home period, followed by 24 total hours in the lab (including a 12-h simulated night shift), ending with 12 h at home. The key difference between the three conditions is the intra-shift nap. Condition 1 will involve a simulated 12-h night shift with total sleep deprivation. Condition 2 will involve a simulated 12-h night shift and a 30-min nap opportunity. Condition 3 will involve a simulated 12-h night shift with a 2-h nap opportunity. Our primary outcomes of interest include blunted BP dipping and reduced HRV as measured by the standard deviation of the inter-beat intervals of normal sinus beats. Non-dipping status will be defined as sleep hours BP dip of less than 10%. Discussion Our study will address two indicators of cardiovascular health and determine if shorter or longer duration naps during night shifts have a clinically meaningful impact. Trial registration ClinicalTrials.gov NCT04469803 . Registered on 9 July 2020
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- 2021
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39. The Clinical Relevance of the NATALEE Study: Application of the NATALEE Criteria to a Real-World Cohort from Two Large German Breast Cancer Centers
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Schäffler, Henning, primary, Mergel, Franziska, additional, Pfister, Kerstin, additional, Lukac, Stephan, additional, Fink, Angelina, additional, Veselinovic, Kristina, additional, Rack, Brigitte, additional, Fink, Visnja, additional, Leinert, Elena, additional, Dimpfl, Moritz, additional, Englisch, Alexander, additional, Tegeler, Christian Martin, additional, Seller, Anna, additional, Grischke, Eva-Maria, additional, Hahn, Markus, additional, Volmer, Léa Louise, additional, Engler, Tobias, additional, Frevert, Marie Louise, additional, Taran, Florin Andrei, additional, Janni, Wolfgang, additional, Brucker, Sara Yvonne, additional, Hartkopf, Andreas Daniel, additional, and Dannehl, Dominik, additional
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- 2023
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40. Situated Conversation: The Role of Attention in Communication
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De Leon, Christian Martin
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Philosophy ,Linguistics ,Psychology ,Attention ,Communication ,Discourse ,Pragmatics ,Salience ,Semantics - Abstract
Regular, everyday conversations do not occur in a vacuum. The physical and social context in which a conversation takes place is utilized through the course of that conversation—it is situated. The ways in which a context can be used vary. Sometimes we implicitly and unconsciously utilize context in interpreting others. While at a restaurant, you would effortlessly interpret “What are you going to have?” not as a general question disconnected from the current situation, but as a question about that particular restaurant’s menu. Other times we overtly utilize context to aid in communication. While out on a walk in the city, I might point to an ice cream cone that has fallen onto the street and say “Somebody’s having a bad day”, and it would be clear what I am talking about.I argue in this dissertation that the psychological category of attention is key for understanding how situated conversations operate. In contrast to viewing communication as a process of pure information exchange, I argue that communication is helpfully analyzed as a process of attention management. Our utterances, gestures, and facial expressions do not serve to merely convey information, but serve to coordinate our attentional states. I begin by focusing on a particular communicative phenomenon that I call rich demonstration. It is, roughly, a deictic (pointing) gesture that functions to communicate an entire thought, in contrast to fixing the reference of a demonstrative expression such as ‘that’. Just by making something salient, one can seemingly say something. I argue that rich demonstration is a speech act in its own right, and provide a formal semantic framework for modeling its communicative effect in discourse.I then proceed to analyze salience itself. The notion has proven useful for understanding a number of communicative phenomena, including reference resolution, certain kinds of pragmatic inference, quantifier domain restriction, and more. Focusing on cases of reference, I argue that the linguistic notion of salience is best understood in terms of the psychological notion of mutual attention. I discuss competing options, including mutual knowledge and varieties of joint attention that are weaker than mutual attention, and argue that only mutual attention suffices for establishing conversational salience. The picture that emerges is one on which conversational moves function in part to coordinate the attentional states of interlocutors.I take advantage of these considerations to argue that discourse information states are genuinely structured—they represent different types of information that can be updated independently. I argue that such structural models of conversation cannot be reasonably reduced to unstructured models, such as the Common Ground model, which flatten discourse information into one kind.This dissertation therefore develops a view of conversation as attention management. This is a perspective on situated conversation on which communicative acts are both restricted by facts about attention and function to coordinate the attentional states of interlocutors.
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- 2022
41. Machine learning-based prediction of acute coronary syndrome using only the pre-hospital 12-lead electrocardiogram
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Salah Al-Zaiti, Lucas Besomi, Zeineb Bouzid, Ziad Faramand, Stephanie Frisch, Christian Martin-Gill, Richard Gregg, Samir Saba, Clifton Callaway, and Ervin Sejdić
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Science - Abstract
Diagnosing a heart attack requires excessive testing and prolonged observation, which frequently requires hospital admission. Here the authors report a machine learning-based system based exclusively on ECG data that can help clinicians identify 37% more heart attacks during initial screening.
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- 2020
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42. Final results from IMPROVE: a randomized, controlled, open-label, two-arm, cross-over phase IV study to determine patients’ preference for everolimus in combination with exemestane or capecitabine in combination with bevacizumab in advanced HR-positive, HER2-negative breast cancer
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Thomas Decker, Ulrike Söling, Antje Hahn, Christoph Maintz, Christian Martin Kurbacher, Ursula Vehling-Kaiser, Dagmar Sent, Peter Klare, Volker Hagen, Marco Chiabudini, Julia Falkenstein, Martin Indorf, Eva Runkel, and Karin Potthoff
- Subjects
Advanced breast Cancer ,Endocrine therapy ,Combined chemo- and anti-Angiogenic therapy ,Patient preference ,Randomized, cross-over phase IV study ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The objective of the IMPROVE study was patients’ preference for either endocrine-based therapy or combined chemo- and anti-angiogenic therapy in advanced HR-positive/HER2-negative breast cancer. Methods In this randomized, cross-over phase IV study, 77 patients were recruited in 26 sites in Germany. Patients were randomized 1:1 to receive either capecitabine plus bevacizumab (Cap+Bev) as first-line therapy followed by cross-over to everolimus plus exemestane (Eve+Exe) as second-line therapy (Arm A) or the reverse sequence (Arm B). The primary endpoint was patients’ preference for either regimen, assessed by the Patient Preference Questionnaire 12 weeks after cross-over. Key secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and quality of life (QoL). Results 61.5% of patients preferred Cap+Bev (p = 0.1653), whereas 15.4% preferred Eve+Exe and 23.1% were indecisive. Physicians showed a similar tendency towards Cap+Bev (58.1%) as the preferred regimen versus Eve+Exe (32.3%). Median first-line PFS was longer for Cap+Bev than for Eve+Exe (11.1 months versus 3.5 months). Median second-line PFS was similar between Cap+Bev and Eve+Exe (3.6 months versus 3.7 months). Median OS was comparable between Arm A (28.8 months) and Arm B (24.7 months). 73.0% and 52.6% (first−/second-line, Cap+Bev) and 54.1% and 52.9% (first−/second-line, Eve+Exe) of patients experienced grade 3/4 TEAEs. No treatment-related deaths occurred. QoL and treatment satisfaction were not significantly different between arms or treatment lines. Conclusions Patients tended to favor Cap+Bev over Eve+Exe, which was in line with physicians’ preference. Cap+Bev showed superior first-line PFS, while QoL was similar in both arms. No new safety signals were reported. Trial registration EudraCT No: 2013–005329-22 . Registered on 19 August 20
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- 2020
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43. Clinical practice guidelines standardisation of immunosuppressive and anti-infective drug regimens in UK paediatric renal transplantation: the harmonisation programme
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Dudley, Jan, Christian, Martin, Andrews, Alice, Andrews, Nicola, Baker, Julie, Boyle, Sheila, Convery, Mairead, Gamston, Fiona, Garcia, Martin, Haq, Shuman, Hegde, Shivaram, Holt, Richard, Jones, Helen, Khan, Shakeeb, McCaughan, Jennifer, Milford, David, Pickles, Charlie, Reynolds, Ben, Sathyanarayana, Vijaya, Stojanovic, Jelena, Tse, Yincent, Wallace, Dean, Walsh, Grainne, Ware, Nick, Williams, Alun, Yadav, Pallavi, and Marks, Stephen
- Published
- 2021
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44. Climate-Optimised Intermediate Stop Operations: Mitigation Potential and Differences from Fuel-Optimised Configuration
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Zarah Lea Zengerling, Florian Linke, Christian Martin Weder, and Katrin Dahlmann
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aviation climate impact ,intermediate stop operations ,mitigation strategies ,operational improvements ,non-CO2 effects ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Saving fuel by splitting a flight mission with an intermediate stop for refuelling is described by the concept of intermediate stop operations. This can also be beneficial to the climate impact of aviation, if the flight level and intermediate stop airport are selected accordingly. This study aims to estimate the mitigation potential of an implementation of climate-optimised intermediate stop operations for European long-haul flights and compare it to fuel-optimal operations. For this purpose, fuel consumption and emissions are simulated along four-dimensional trajectories for the selected annual flight plan, and their average temperature response is calculated. A comparison between the reference case and climate-optimised as well as fuel-optimised scenarios shows a significant climate mitigation potential and reveals a shift of trajectories to lower latitudes and altitudes. However, increased flight times and fuel consumption limit implementation from stakeholders’ perspectives.
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- 2022
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45. Immunomonitoring of Stage IV Relapsed Neuroblastoma Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation and Subsequent GD2 (ch14.18/CHO) Antibody Treatment
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Christian Martin Seitz, Tim Flaadt, Markus Mezger, Anne-Marie Lang, Sebastian Michaelis, Marie Katz, Desireé Syring, Alexander Joechner, Armin Rabsteyn, Nikolai Siebert, Sascha Troschke-Meurer, Maxi Zumpe, Holger N. Lode, Sile F. Yang, Daniel Atar, Anna-Sophia Mast, Sophia Scheuermann, Florian Heubach, Rupert Handgretinger, Peter Lang, and Patrick Schlegel
- Subjects
neuroblastoma ,immunomonitoring immunotherapy ,GD2 antibody therapy ,haploidentical allogeneic stem cell transplantation ,antibody-dependent cellular cytotoxicity ,complement-dependent cytotoxicity ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Haploidentical stem cell transplantation (haplo SCT) in Stage IV neuroblastoma relapsed patients has been proven efficacious, while immunotherapy utilizing the anti-GD2 antibody dinutuximab beta has become a standard treatment for neuroblastoma. The combinatorial therapy of haplo SCT and dinutuximab may potentiate the efficacy of the immunotherapy. To gain further understanding of the synergistic effects, functional immunomonitoring was assessed during the clinical trial CH14.18 1021 Antibody and IL2 After haplo SCT in Children with Relapsed Neuroblastoma (NCT02258815). Rapid immune reconstitution of the lymphoid compartment was confirmed, with clinically relevant dinutuximab serum levels found in all patients over the course of treatment. Only one patient developed human anti-chimeric antibodies (HACAs). In-patient monitoring revealed highly functional NK cell posttransplant capable of antibody-dependent cellular cytotoxicity (ADCC). Degranulation of NK cell subsets revealed a significant response increased by dinutuximab. This was irrespective of the KIR receptor–ligand constellation within the NK subsets, defined by the major KIR receptors CD158a, CD158b, and CD158e. Moreover, complement-dependent cytotoxicity (CDC) was shown to be an extremely potent effector-cell independent mechanism of tumor cell lysis, with a clear positive correlation to GD2 expression on the cancer cells as well as to the dinutuximab concentrations. The ex vivo testing of patient-derived effector cells and the sera collected during dinutuximab therapy demonstrated both high functionality of the newly established lymphoid immune compartment and provided confidence that the antibody dosing regimen was sufficient over the duration of the dinutuximab therapy (up to nine cycles in a 9-month period). During the course of the dinutuximab therapy, proinflammatory cytokines and markers (sIL2R, TNFa, IL6, and C reactive protein) were significantly elevated indicating a strong anti-GD2 immune response. No impact of FcGR polymorphism on event-free and overall survival was found. Collectively, this study has shown that in-patient functional immunomonitoring is feasible and valuable in contributing to the understanding of anti-cancer combinatorial treatments such as haplo SCT and antibody immunotherapy.
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- 2021
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46. Consensus Standard for Evidence Integration into EMS Education and High-Stakes Testing
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Christopher B. Gage, Mark Terry, Kim D. McKenna, Jonathan R. Powell, Megan Hollern, Matt Ozanich, Christopher T. Richards, Christian Martin-Gill, and Ashish R. Panchal
- Subjects
Emergency Medicine ,Emergency Nursing - Abstract
Background: Incorporating emerging knowledge into Emergency Medical Service (EMS) competency assessments is critical to reflect current evidence-based out-of-hospital care. However, a standardized approach is needed to incorporate new evidence into EMS competency assessments because of the rapid pace of knowledge generation. Objective: The objective was to develop a framework to evaluate and integrate new source material into EMS competency assessments. Methods: The National Registry of Emergency Medical Technicians (National Registry) and the Prehospital Guidelines Consortium (PGC) convened a panel of experts. A Delphi method, consisting of virtual meetings and electronic surveys, was used to develop a Table of Evidence matrix that defines sources of EMS evidence. In Round One, participants listed all potential sources of evidence available to inform EMS education. In Round Two, participants categorized these sources into: (a) levels of evidence quality; and (b) type of source material. In Round Three, the panel revised a proposed Table of Evidence. Finally, in Round Four, participants provided recommendations on how each source should be incorporated into competency assessments depending on type and quality. Descriptive statistics were calculated with qualitative analyses conducted by two independent reviewers and a third arbitrator. Results: In Round One, 24 sources of evidence were identified. In Round Two, these were classified into high- (n = 4), medium- (n = 15), and low-quality (n = 5) of evidence, followed by categorization by purpose into providing recommendations (n = 10), primary research (n = 7), and educational content (n = 7). In Round Three, the Table of Evidence was revised based on participant feedback. In Round Four, the panel developed a tiered system of evidence integration from immediate incorporation of high-quality sources to more stringent requirements for lower-quality sources. Conclusion: The Table of Evidence provides a framework for the rapid and standardized incorporation of new source material into EMS competency assessments. Future goals are to evaluate the application of the Table of Evidence framework in initial and continued competency assessments.
- Published
- 2023
47. Prehospital Stroke Care Part 2: On-Scene Evaluation and Management by Emergency Medical Services Practitioners
- Author
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Christopher T. Richards, J. Adam Oostema, Sherita N. Chapman, Lauren E. Mamer, Ethan S. Brandler, Anne W. Alexandrov, Alexandra L. Czap, Juan Carlos Martinez-Gutierrez, Christian Martin-Gill, Ashish R. Panchal, Jason T. McMullan, and Kori S. Zachrison
- Subjects
Advanced and Specialized Nursing ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine - Abstract
The prehospital phase is a critical component of delivering high-quality acute stroke care. This topical review discusses the current state of prehospital acute stroke screening and transport, as well as new and emerging advances in prehospital diagnosis and treatment of acute stroke. Topics include prehospital stroke screening, stroke severity screening, emerging technologies to aid in the identification and diagnosis of acute stroke in the prehospital setting, prenotification of receiving emergency departments, decision support for destination determination, and the capabilities and opportunities for prehospital stroke treatment in mobile stroke units. Further evidence-based guideline development and implementation of new technologies are critical for ongoing improvements in prehospital stroke care.
- Published
- 2023
48. Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas
- Author
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Daniel Atar, Anna-Sophia Mast, Sophia Scheuermann, Lara Ruoff, Christian Martin Seitz, and Patrick Schlegel
- Subjects
adapter CAR T cell ,immune escape ,combinatorial immunotargeting ,B-cell lymphoma ,Biology (General) ,QH301-705.5 - Abstract
CD19CAR T cells facilitate a transformational treatment in various relapsed and refractory aggressive B-lineage cancers. In general, encouraging response rates have been observed in B-lineage-derived non-Hodgkin’s lymphomas treated with CD19CAR T cells. The major cause of death in heavily pretreated NHL patients is lymphoma progression and lymphoma recurrence. Inefficient CAR T cell therapy is the result of the limited potency of the CAR T cell product or is due to loss of the targeted antigen. Target antigen loss has been identified as the key factor that can be addressed stringently by dual- or multitargeted CAR T cell approaches. We have developed a versatile adapter CAR T cell technology (AdCAR) that allows multitargeting. Screening of three different B-lineage lymphoma cell lines has revealed distinct immune target profiles. Cancer-specific adapter molecule combinations may be utilized to prevent antigen immune escape. In general, CD19CAR T cells become non-functional in CD19 negative lymphoma subsets; however, AdCAR T cells can be redirected to alternative target antigens beyond CD19, such as CD20, CD22, CD79B, and ROR-1. The capability to flexibly shift CAR specificity by exchanging the adapter molecule’s specificity broadens the application and significantly increases the anti-leukemic and anti-lymphoma activity. The clinical evaluation of AdCAR T cells in lymphoma as a new concept of CAR T cell immunotherapy may overcome treatment failure due to antigen immune escape in monotargeted conventional CAR T cell therapies.
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- 2022
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49. Welding Fume Instillation in Isolated Perfused Mouse Lungs—Effects of Zinc- and Copper-Containing Welding Fumes
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Julia Krabbe, Thomas Kraus, Hanif Krabbe, Christian Martin, and Patrick Ziegler
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isolated perfused lung ,welding fumes ,zinc ,copper ,myeloperoxidase ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Zinc- and copper-containing welding fumes can cause systemic inflammation after exposure in humans. Recent ex vivo studies have shown that the observed inflammation originates from exposed immune cells. In vitro studies identified the soluble fraction of metal particles as the main effectors. Isolated perfused mouse lungs (IPLs) were perfused and ventilated for 270 min. Lungs were instilled with saline solution (control), welding fume particle suspension (WFs) or the soluble fraction of the welding fumes (SF-WFs). Bronchoalveolar lavage fluid (BALF) and perfusate samples were analyzed for cytokine levels and lung tissue mRNA expression levels were analyzed via RT-PCR. All lungs instilled with WFs did not complete the experiments due to a fatal reduction in tidal volume. Accordingly, IL-6 and MPO levels were significantly higher in BALF of WF lungs compared to the control. IL-6 and MPO mRNA expression levels were also increased for WFs. Lungs instilled with SF-WFs only showed mild reactions in tidal volume, with BALF and mRNA expression levels not significantly differing from the control. Zinc- and copper-containing welding fume particles adversely affect IPLs when instilled, as evidenced by the fatal loss in tidal volume and increased cytokine expression and secretion. The effects are mainly caused by the particles, not by the soluble fraction.
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- 2022
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50. Early conversion of pediatric kidney transplant patients to everolimus with reduced tacrolimus and steroid elimination: Results of a randomized trial
- Author
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Tönshoff, Burkhard, Ettenger, Robert, Dello Strologo, Luca, Marks, Stephen D., Pape, Lars, Tedesco-Silva, Helio, Jr, Bjerre, Anna, Christian, Martin, Meier, Matthias, Martzloff, El-Djouher, Rauer, Barbara, Ng, Jennifer, and Lopez, Patricia
- Published
- 2019
- Full Text
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