2,188 results on '"Diacon A"'
Search Results
2. A first-in-class leucyl-tRNA synthetase inhibitor, ganfeborole, for rifampicin-susceptible tuberculosis: a phase 2a open-label, randomized trial
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Diacon, Andreas H., Barry, III, Clifton E., Carlton, Alex, Chen, Ray Y., Davies, Matt, de Jager, Veronique, Fletcher, Kim, Koh, Gavin C. K. W., Kontsevaya, Irina, Heyckendorf, Jan, Lange, Christoph, Reimann, Maja, Penman, Sophie L., Scott, Rhona, Maher-Edwards, Gareth, Tiberi, Simon, Vlasakakis, Georgios, Upton, Caryn M., and Aguirre, David Barros
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- 2024
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3. Nanoparticles synthesis by electron beam radiolysis
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Călinescu Ioan, Martin Diana, Ighigeanu Daniel, Gavrila Adina, Trifan Adrian, Patrascu Mariana, Munteanu Cornel, Diacon Aurel, Manaila Elena, and Craciun Gabriela
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silver nanoparticles ,electron beam ,radiolysis ,Chemistry ,QD1-999 - Published
- 2014
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4. Photonic crystals obtained by soap-free emulsion terpolymerization
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Rusen Edina, Diacon Aurel, and Mocanu Alexandra
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Soap-free emulsion terpolymerization ,Photonic crystals ,Band gap ,Water soluble monomers ,Chemistry ,QD1-999 - Published
- 2014
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5. Co-regulation of innate and adaptive immune responses induced by ID93+GLA-SE vaccination in humans
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Andrew Fiore-Gartland, Himangi Srivastava, Aaron Seese, Tracey Day, Adam Penn-Nicholson, Angelique Kany Kany Luabeya, Nelita Du Plessis, Andre G. Loxton, Linda-Gail Bekker, Andreas Diacon, Gerhard Walzl, Zachary K. Sagawa, Steven G. Reed, Thomas J. Scriba, Mark Hatherill, and Rhea Coler
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tuberculosis ,vaccines ,systems immunology ,innate ,RNA sequencing ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionDevelopment of an effective vaccine against tuberculosis is a critical step towards reducing the global burden of disease. A therapeutic vaccine might also reduce the high rate of TB recurrence and help address the challenges of drug-resistant strains. ID93+GLA-SE is a candidate subunit vaccine that will soon be evaluated in a phase 2b efficacy trial for prevention of recurrent TB among patients undergoing TB treatment. ID93+GLA-SE vaccination was shown to elicit robust CD4+ T cell and IgG antibody responses among recently treated TB patients in the TBVPX-203 Phase 2a study (NCT02465216), but the mechanisms underlying these responses are not well understood.MethodsIn this study we used specimens from TBVPX-203 participants to describe the changes in peripheral blood gene expression that occur after ID93+GLA-SE vaccination.ResultsAnalyses revealed several distinct modules of co-varying genes that were either up- or down-regulated after vaccination, including genes associated with innate immune pathways at 3 days post-vaccination and genes associated with lymphocyte expansion and B cell activation at 7 days post-vaccination. Notably, the regulation of these gene modules was affected by the dose schedule and by participant sex, and early innate gene signatures were correlated with the ID93-specific CD4+ T cell response.DiscussionThe results provide insight into the complex interplay of the innate and adaptive arms of the immune system in developing responses to vaccination with ID93+GLA-SE and demonstrate how dosing and schedule can affect vaccine responses.
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- 2024
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6. Automatic Tuberculosis and COVID-19 cough classification using deep learning
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Pahar, Madhurananda, Klopper, Marisa, Reeve, Byron, Warren, Rob, Theron, Grant, Diacon, Andreas, and Niesler, Thomas
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Computer Science - Machine Learning ,Computer Science - Sound ,Electrical Engineering and Systems Science - Audio and Speech Processing ,Quantitative Biology - Quantitative Methods - Abstract
We present a deep learning based automatic cough classifier which can discriminate tuberculosis (TB) coughs from COVID-19 coughs and healthy coughs. Both TB and COVID-19 are respiratory diseases, contagious, have cough as a predominant symptom and claim thousands of lives each year. The cough audio recordings were collected at both indoor and outdoor settings and also uploaded using smartphones from subjects around the globe, thus containing various levels of noise. This cough data include 1.68 hours of TB coughs, 18.54 minutes of COVID-19 coughs and 1.69 hours of healthy coughs from 47 TB patients, 229 COVID-19 patients and 1498 healthy patients and were used to train and evaluate a CNN, LSTM and Resnet50. These three deep architectures were also pre-trained on 2.14 hours of sneeze, 2.91 hours of speech and 2.79 hours of noise for improved performance. The class-imbalance in our dataset was addressed by using SMOTE data balancing technique and using performance metrics such as F1-score and AUC. Our study shows that the highest F1-scores of 0.9259 and 0.8631 have been achieved from a pre-trained Resnet50 for two-class (TB vs COVID-19) and three-class (TB vs COVID-19 vs healthy) cough classification tasks, respectively. The application of deep transfer learning has improved the classifiers' performance and makes them more robust as they generalise better over the cross-validation folds. Their performances exceed the TB triage test requirements set by the world health organisation (WHO). The features producing the best performance contain higher order of MFCCs suggesting that the differences between TB and COVID-19 coughs are not perceivable by the human ear. This type of cough audio classification is non-contact, cost-effective and can easily be deployed on a smartphone, thus it can be an excellent tool for both TB and COVID-19 screening., Comment: This paper has been published in 2022 International Conference on Electrical, Computer and Energy Technologies (ICECET)
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- 2022
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7. Accelerometer-based Bed Occupancy Detection for Automatic, Non-invasive Long-term Cough Monitoring
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Pahar, Madhurananda, Miranda, Igor, Diacon, Andreas, and Niesler, Thomas
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Computer Science - Machine Learning - Abstract
We present a new machine learning based bed-occupancy detection system that uses the accelerometer signal captured by a bed-attached consumer smartphone. Automatic bed-occupancy detection is necessary for automatic long-term cough monitoring, since the time which the monitored patient occupies the bed is required to accurately calculate a cough rate. Accelerometer measurements are more cost effective and less intrusive than alternatives such as video monitoring or pressure sensors. A 249-hour dataset of manually-labelled acceleration signals gathered from seven patients undergoing treatment for tuberculosis (TB) was compiled for experimentation. These signals are characterised by brief activity bursts interspersed with long periods of little or no activity, even when the bed is occupied. To process them effectively, we propose an architecture consisting of three interconnected components. An occupancy-change detector locates instances at which bed occupancy is likely to have changed, an occupancy-interval detector classifies periods between detected occupancy changes and an occupancy-state detector corrects falsely-identified occupancy changes. Using long short-term memory (LSTM) networks, this architecture was demonstrated to achieve an AUC of 0.94. When integrated into a complete cough monitoring system, the daily cough rate of a patient undergoing TB treatment was determined over a period of 14 days. As the colony forming unit (CFU) counts decreased and the time to positivity (TPP) increased, the measured cough rate decreased, indicating effective TB treatment. This provides a first indication that automatic cough monitoring based on bed-mounted accelerometer measurements may present a non-invasive, non-intrusive and cost-effective means of monitoring long-term recovery of TB patients.
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- 2022
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8. High Asymptomatic Carriage With the Omicron Variant in South Africa
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Garrett, Nigel, Tapley, Asa, Andriesen, Jessica, Seocharan, Ishen, Fisher, Leigh H, Bunts, Lisa, Espy, Nicole, Wallis, Carole L, Randhawa, April Kaur, Miner, Maurine D, Ketter, Nzeera, Yacovone, Margaret, Goga, Ameena, Huang, Yunda, Hural, John, Kotze, Philip, Bekker, Linda Gail, Gray, Glenda E, Corey, Lawrence, Ahmed, Khatija, Badal-Faesen, Sharlaa, Barnabas, Shaun, Brumskine, William, Comline, Kim, Diacon, Andreas, Dubula, Thozama, Gill, Katherine, Grobbelaar, Coert, Innes, Craig, Kassim, Sheetal, Kotze, Sheena, Lazarus, Erica, Lombaard, Johannes, Luabeya, Angelique, Maboa, Rebone Molobane, Mahoney, Scott, Mahkaza, Disebo, Malahleha, Moelo, Malan, Daniel, Mngadi, Kathryn, Naicker, Nivashnee, Naicker, Vimla, Naidoo, Logashvari, Nchabeleng, Maphoshane, Rassool, Mohammed, Spooner, Elizabeth, Tempelman, Hugo, Mgodi, Nyaradzo, Dadabhai, Sufia, Makhema, Joe, Nuwagaba-Biribonwoha, Harriet, Samandari, Taraz, Elyanu, Peter James, Chilengi, Roma, Chirenje, Zvavahera, McElrath, Julie, Cohen, Myron, Kublin, James, Gilbert, Peter, Peda, Melissa, Andersen-Nissen, Erica, Ferrari, Guido, Villaran, Manuel, Takalani, Azwidhwi, Gildea, Marianne, Nebergall, Michelle, Sopher, Carrie, Proulx-Burns, Lori, Govender, Dhevium, Sanders, Lisa, Hanke, Jen, Baepanye, Kagisho, Le Roux, Bert, Wilvich, Haven, Sripathy, Smitha, Margineantu, Daciana, Brown, Valerie, Linton, Kim, Howell, Haley, Noronha, Bianca, Nikles, Sarah, Toledano, Alicia, May, Jeanine, El-Khorazaty, Jill, Naidoo, Keshani, Khuto, Kentse, Mayat, Fatima, Fairall, Lara, and Sanne, Ian
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Medical Microbiology ,Biomedical and Clinical Sciences ,Pneumonia & Influenza ,Infectious Diseases ,Vaccine Related ,Lung ,Prevention ,Emerging Infectious Diseases ,Clinical Research ,Pneumonia ,Biodefense ,Clinical Trials and Supportive Activities ,Infection ,Good Health and Well Being ,COVID-19 ,Humans ,Polymerase Chain Reaction ,SARS-CoV-2 ,South Africa ,Omicron variant ,asymptomatic carriage ,PWH ,Ubuntu Study Team ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
We report a 23% asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) Omicron carriage rate in participants being enrolled into a clinical trial in South Africa, 15-fold higher than in trials before Omicron. We also found lower CD4 + T-cell counts in persons with human immunodeficiency virus (HIV) strongly correlated with increased odds of being SARS-CoV-2 polymerase chain reaction (PCR) positive.
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- 2022
9. Quabodepistat in combination with delamanid and bedaquiline in participants with drug-susceptible pulmonary tuberculosis: protocol for a multicenter, phase 2b/c, open-label, randomized, dose-finding trial to evaluate safety and efficacy
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Rodney Dawson, Andreas H. Diacon, Simbarashe Takuva, Yongge Liu, Bo Zheng, Vatsala Karwe, and Jeffrey Hafkin
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Antituberculosis agent ,Bedaquiline ,Delamanid ,DprE1 inhibitor ,Drug-sensitive tuberculosis ,Quabodepistat ,Medicine (General) ,R5-920 - Abstract
Abstract Background Delamanid and bedaquiline are two of the most recently developed antituberculosis (TB) drugs that have been extensively studied in patients with multidrug-resistant TB. There is currently a need for more potent, less-toxic drugs with novel mechanisms of action that can be used in combination with these newer agents to shorten the duration of treatment as well as prevent the development of drug resistance. Quabodepistat (QBS) is a newly discovered inhibitor of decaprenylphosphoryl-β-D-ribose-2′-oxidase, an essential enzyme for Mycobacterium tuberculosis to synthesize key components of its cell wall. The objective of this study is to evaluate the safety, efficacy, and appropriate dosing of a 4-month regimen of QBS in combination with delamanid and bedaquiline in participants with drug-susceptible pulmonary TB in comparison with the 6-month standard treatment (i.e., rifampicin, isoniazid, ethambutol, and pyrazinamide). Methods This phase 2b/c, open-label, randomized, parallel group, dose-finding trial will enroll approximately 120 participants (including no more than 15% with human immunodeficiency virus [HIV] coinfection) aged ≥ 18 to ≤ 65 years at screening with newly diagnosed pulmonary drug-sensitive TB from ~8 sites in South Africa. Following a screening period of up to 14 days, eligible participants will be randomized in a ratio of 1:2:2:1 to one of four arms. Randomization will be stratified by HIV status and the presence of bilateral cavitation on a screening chest x-ray. After the end of the treatment period, participants will be followed until 12 months post randomization. The primary efficacy endpoint is the proportion of participants achieving sputum culture conversion in Mycobacteria Growth Indicator Tube by the end of the treatment period. The safety endpoints consist of adverse events, clinical laboratory tests, vital signs, physical examination findings, and electrocardiographic changes. Discussion QBS’s potent bactericidal activity and distinct mechanism of action (compared with other TB drugs currently available for human use) may make it an ideal candidate for inclusion in a novel treatment regimen to improve efficacy and potentially prevent resistance to concomitant TB drugs. This trial will assess the effectiveness, safety, and dosing of a new, shorter, QBS-based, combination anti-TB treatment regimen. Trial status ClinicalTrials.gov NCT05221502. Registered on February 3, 2022
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- 2024
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10. Experimental Investigations on Shear Thickening Fluids as 'Liquid Body Armors': Non-Conventional Formulations for Ballistic Protection
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Florentina Alexe, Ciprian Sau, Ovidiu Iorga, Gabriela Toader, Aurel Diacon, Edina Rusen, Claudiu Lazaroaie, Raluca Elena Ginghina, Tudor Viorel Tiganescu, Mircea Teodorescu, and Arcadie Sobetkii
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shear thickening fluids ,polymers ,composites ,ballistic protection ,liquid armor ,Organic chemistry ,QD241-441 - Abstract
Shear thickening fluids (STFs) have garnered attention as potential enhancers of protective capabilities and for the optimization of Kevlar® armor design. To assess the possible shear thickening properties and potential application in ballistic protection, ten formulations were developed by employing polyethylene glycol (PEG) or polypropylene glycol (PPG), along with fumed silica or Aerosil HDK®. Rheological characterization facilitated the identification of formulations displaying shear thickening behavior. The potential integration of the selected shear thickening fluids (STFs) into Kevlar®-based composites was investigated by studying the impact resistance of Kevlar® soft armor structures. Also, high-velocity impact testing revealed that the distance between aramid layers plays a crucial role in the impact resistance effectiveness of Kevlar®–STF composite structures and that there is a very narrow domain between optimal and undesired scenarios in which STF could facilitate the penetration of Kevlar. The introduction of STF between the Kevlar sheets disrupted this packing and the energy absorption capacity of the material was not improved. Only one formulation (PEG400, Aerosil 27 wt.%) led to a less profound traumatic imprint and stopped the bullet when it was placed between layers no.1 and no.2 from a total of 11 layers of Kevlar XP. These experimental findings align with the modeling and simulation of Kevlar®–STF composites using Ansys simulation software (Ansys® AutoDyn 2022 R2).
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- 2024
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11. Mentoring Valorization in Combating Violent and Aggressive Behaviour in Preadolescence and Adolescence
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Antoci, Diana, Mislitchi, Valentina, and Diacon, Maria
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The present work combats the problem of violence and aggressive behaviour through mentoring. The theoretical point of view certified studies that highlight various aspects of the problem of violent and aggressive behaviour remediation of preadolescents and adolescents. At present there are no publications that completely synthesize the institutional and normative field of mentoring. The existing publications reference to the regulation regarding the establishment of the mentoring system for teaching staff in education. Thus, the problem of mentoring valorization in combating violent behaviour among preadolescents and adolescents remains unresolved. The viable solution to solving these actual problems of the postmodern world is to focus on the personality value system.
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- 2020
12. Wake-Cough: cough spotting and cougher identification for personalised long-term cough monitoring
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Pahar, Madhurananda, Klopper, Marisa, Reeve, Byron, Warren, Rob, Theron, Grant, Diacon, Andreas, and Niesler, Thomas
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Computer Science - Sound ,Computer Science - Machine Learning ,Electrical Engineering and Systems Science - Audio and Speech Processing - Abstract
We present `wake-cough', an application of wake-word spotting to coughs using a Resnet50 and the identification of coughers using i-vectors, for the purpose of a long-term, personalised cough monitoring system. Coughs, recorded in a quiet (73$\pm$5 dB) and noisy (34$\pm$17 dB) environment, were used to extract i-vectors, x-vectors and d-vectors, used as features to the classifiers. The system achieves 90.02\% accuracy when using an MLP to discriminate between 51 coughers using 2-sec long cough segments in the noisy environment. When discriminating between 5 and 14 coughers using longer (100 sec) segments in the quiet environment, this accuracy improves to 99.78% and 98.39% respectively. Unlike speech, i-vectors outperform x-vectors and d-vectors in identifying coughers. These coughs were added as an extra class to the Google Speech Commands dataset and features were extracted by preserving the end-to-end time-domain information in a trigger phrase. The highest accuracy of 88.58% is achieved in spotting coughs among 35 other trigger phrases using a Resnet50. Thus, wake-cough represents a personalised, non-intrusive cough monitoring system, which is power-efficient as on-device wake-word detection can keep a smartphone-based monitoring device mostly dormant. This makes wake-cough extremely attractive in multi-bed ward environments to monitor patients' long-term recovery from lung ailments such as tuberculosis (TB) and COVID-19.
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- 2021
13. Automatic non-invasive Cough Detection based on Accelerometer and Audio Signals
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Pahar, Madhurananda, Miranda, Igor, Diacon, Andreas, and Niesler, Thomas
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Computer Science - Sound ,Computer Science - Artificial Intelligence ,Computer Science - Machine Learning ,Electrical Engineering and Systems Science - Audio and Speech Processing - Abstract
We present an automatic non-invasive way of detecting cough events based on both accelerometer and audio signals. The acceleration signals are captured by a smartphone firmly attached to the patient's bed, using its integrated accelerometer. The audio signals are captured simultaneously by the same smartphone using an external microphone. We have compiled a manually-annotated dataset containing such simultaneously-captured acceleration and audio signals for approximately 6000 cough and 68000 non-cough events from 14 adult male patients in a tuberculosis clinic. LR, SVM and MLP are evaluated as baseline classifiers and compared with deep architectures such as CNN, LSTM, and Resnet50 using a leave-one-out cross-validation scheme. We find that the studied classifiers can use either acceleration or audio signals to distinguish between coughing and other activities including sneezing, throat-clearing, and movement on the bed with high accuracy. However, in all cases, the deep neural networks outperform the shallow classifiers by a clear margin and the Resnet50 offers the best performance by achieving an AUC exceeding 0.98 and 0.99 for acceleration and audio signals respectively. While audio-based classification consistently offers a better performance than acceleration-based classification, we observe that the difference is very small for the best systems. Since the acceleration signal requires less processing power, and since the need to record audio is sidestepped and thus privacy is inherently secured, and since the recording device is attached to the bed and not worn, an accelerometer-based highly accurate non-invasive cough detector may represent a more convenient and readily accepted method in long-term cough monitoring., Comment: arXiv admin note: text overlap with arXiv:2102.04997
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- 2021
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14. Reproducibility in pharmacometrics applied in a phase III trial of BCG-vaccination for COVID-19
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van Wijk, Rob C., Mockeliunas, Laurynas, van den Hoogen, Gerben, Upton, Caryn M., Diacon, Andreas H., and Simonsson, Ulrika S. H.
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- 2023
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15. Suspension Photopolymerization of Methyl Methacrylate and ATRP Grafting of Thermo‐Responsive Polymers Using a Perylediimide Derivative Photoinitiator
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Aurel Diacon, Florica Rizea, Alexandra Mocanu, Adrian Dinescu, Cristina Stavarache, Luiza Izabela Jinga, Cristian N. Mihăilescu, and Edina Rusen
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atom transfer radical polymerization (ATRP) ,photopolymerization ,photoredox ,photosensitizers ,surface‐initiated ATRP ,suspension polymerization ,Materials of engineering and construction. Mechanics of materials ,TA401-492 ,Engineering (General). Civil engineering (General) ,TA1-2040 - Abstract
Abstract The first aim of this study is to develop a photo‐ATRP process using methyl methacrylate (MMA) by employing a novel perylenediimide derivative (PDI) as photoinitiator. The analysis of the MMA photopolymerization process kinetics is performed in solution and in bulk, demonstrating control over the reaction progress even if the polymerizations display a slow initiation step. The photo‐ATRP process for MMA in suspension is also developed and the obtained PMMA particles are further used to reinitiate the ATRP polymerization of thermoresponsive polymers (different molecular weights poly(ethylene glycol) methyl ether methacrylate and poly(N‐isopropylacrylamide)) (PNIPAM) in solution and surface‐initiated processes. The synthesized polymers by surface‐initiated process display a bimodal molecular weight distribution with a clear modification of the signal areas ratio depending on the grafted monomer and on the reaction conditions. The grafting process can take place on the surface of the polymer particles (Mn2), or it can also involve polymer chains located further at the interior of the polymer particles (Mn1). The lower critical solution temperature (LCST) transition is demonstrated for the PNIPAM functionalized polymer particles.
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- 2024
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16. Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment
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Georghiou, Sophia B, Rodwell, Timothy C, Korobitsyn, Alexei, Abbadi, Said H, Ajbani, Kanchan, Alffenaar, Jan-Willem, Alland, David, Alvarez, Nataly, Andres, Sönke, Ardizzoni, Elisa, Aubry, Alexandra, Baldan, Rossella, Ballif, Marie, Barilar, Ivan, Böttger, Erik C, Chakravorty, Soumitesh, Claxton, Pauline M, Cirillo, Daniela M, Comas, Iñaki, Coulter, Chris, Denkinger, Claudia M, Derendinger, Brigitta, Desmond, Edward P, de Steenwinkel, Jurriaan EM, Dheda, Keertan, Diacon, Andreas H, Dolinger, David L, Dooley, Kelly E, Egger, Matthias, Ehsani, Soudeh, Farhat, Maha R, Fattorini, Lanfranco, Finci, Iris, Le Ray, Laure Fournier, Furió, Victoria, Groenheit, Ramona, Gumbo, Tawanda, Heysell, Scott K, Hillemann, Doris, Hoffmann, Harald, Hsueh, Po-Ren, Hu, Yi, Huang, Hairong, Hussain, Alamdar, Ismail, Farzana, Izumi, Kiyohiko, Jagielski, Tomasz, Johnson, John L, Kambli, Priti, Kaniga, Koné, Karunaratne, GHR Eranga, Sharma, Meenu Kaushal, Keller, Peter M, Kelly, Ellis C, Kholina, Margarita, Kohli, Mikashmi, Kranzer, Katharina, Laurenson, Ian F, Limberis, Jason, Lin, S-Y Grace, Liu, Yongge, López-Gavín, Alexandre, Lyander, Anna, Machado, Diana, Martinez, Elena, Masood, Faisal, Mitarai, Satoshi, Mvelase, Nomonde R, Niemann, Stefan, Nikolayevskyy, Vladyslav, Maurer, Florian P, Merker, Matthias, Miotto, Paolo, Omar, Shaheed V, Otto-Knapp, Ralf, Palaci, Moisés, Gutiérrez, Juan José Palacios, Peacock, Sharon J, Peloquin, Charles A, Perera, Jennifer, Pierre-Audigier, Catherine, Pholwat, Suporn, Posey, James E, Prammananan, Therdsak, Rigouts, Leen, Robledo, Jaime, Rockwood, Neesha, Rodrigues, Camilla, Salfinger, Max, Schechter, Marcos C, Seifert, Marva, Sengstake, Sarah, Shinnick, Thomas, Shubladze, Natalia, Sintchenko, Vitali, Sirgel, Frederick, Somasundaram, Sulochana, Sterling, Timothy R, Spitaleri, Andrea, and Streicher, Elizabeth
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Infectious Diseases ,Biodefense ,Antimicrobial Resistance ,Prevention ,Rare Diseases ,Emerging Infectious Diseases ,Tuberculosis ,Clinical Research ,Vaccine Related ,Orphan Drug ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,Antitubercular Agents ,Drug Resistance ,Bacterial ,Drug Resistance ,Multiple ,Bacterial ,Humans ,Microbial Sensitivity Tests ,Mycobacterium tuberculosis ,Tuberculosis ,Multidrug-Resistant ,Antimycobacterial Susceptibility Testing Group ,Medical and Health Sciences ,Respiratory System ,Cardiovascular medicine and haematology - Abstract
Inappropriately high breakpoints have resulted in systematic false-susceptible AST results to anti-TB drugs. MIC, PK/PD and clinical outcome data should be combined when setting breakpoints to minimise the emergence and spread of antimicrobial resistance. https://bit.ly/3i43wb6
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- 2022
17. Improved degradability and mechanical properties of bacterial cellulose grafted with PEG derivatives
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Rusen, Edina, Isopencu, Gabriela, Toader, Gabriela, Diacon, Aurel, Dinescu, Adrian, and Mocanu, Alexandra
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- 2023
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18. The influence of the 8OCB liquid crystal concentrations on the ST-AA photonic crystal synthesis
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Rusen, Edina, Mocanu, Alexandra, Brincoveanu, Oana, Boldeiu, Adina, Mitran, Raul-Augustin, Toader, Gabriela, and Diacon, Aurel
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- 2024
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19. Deep Neural Network based Cough Detection using Bed-mounted Accelerometer Measurements
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Pahar, Madhurananda, Miranda, Igor, Diacon, Andreas, and Niesler, Thomas
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Computer Science - Machine Learning ,Computer Science - Sound ,Electrical Engineering and Systems Science - Audio and Speech Processing - Abstract
We have performed cough detection based on measurements from an accelerometer attached to the patient's bed. This form of monitoring is less intrusive than body-attached accelerometer sensors, and sidesteps privacy concerns encountered when using audio for cough detection. For our experiments, we have compiled a manually-annotated dataset containing the acceleration signals of approximately 6000 cough and 68000 non-cough events from 14 adult male patients in a tuberculosis clinic. As classifiers, we have considered convolutional neural networks (CNN), long-short-term-memory (LSTM) networks, and a residual neural network (Resnet50). We find that all classifiers are able to distinguish between the acceleration signals due to coughing and those due to other activities including sneezing, throat-clearing and movement in the bed with high accuracy. The Resnet50 performs the best, achieving an area under the ROC curve (AUC) exceeding 0.98 in cross-validation experiments. We conclude that high-accuracy cough monitoring based only on measurements from the accelerometer in a consumer smartphone is possible. Since the need to gather audio is avoided and therefore privacy is inherently protected, and since the accelerometer is attached to the bed and not worn, this form of monitoring may represent a more convenient and readily accepted method of long-term patient cough monitoring., Comment: It has been accepted in ICASSP, 2021. Copyright information is shown at the very first page
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- 2021
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20. Ionic Crosslinked Hydrogel Films for Immediate Decontamination of Chemical Warfare Agents
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Gabriela Toader, Raluca-Elena Ginghina, Adriana Elena Bratu, Alice Ionela Podaru, Daniela Pulpea, Traian Rotariu, Ana Mihaela Gavrilă, and Aurel Diacon
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hydrogels ,mustard gas decontamination ,photocatalytic degradation ,mechanical properties of hydrogels ,ionic crosslinking ,Science ,Chemistry ,QD1-999 ,Inorganic chemistry ,QD146-197 ,General. Including alchemy ,QD1-65 - Abstract
This study describes the development of hydrogel formulations with ionic crosslinking capacity and photocatalytic characteristics. The objective of this research is to provide an effective, accessible, “green”, and facile route for the decontamination of chemical warfare agents (CWAs, namely the blistering agent—mustard gas/sulfur mustard (HD)) from contaminated surfaces, by decomposition and entrapment of CWAs and their degradation products inside the hydrogel films generated “on-site”. The decontamination of the notorious warfare agent HD was successfully achieved through a dual hydrolytic–photocatalytic degradation process. Subsequently, the post-decontamination residues were encapsulated within a hydrogel membrane film produced via an ionic crosslinking mechanism. Polyvinyl alcohol (PVA) and sodium alginate (ALG) are the primary constituents of the decontaminating formulations. These polymeric components were chosen for this application due to their cost-effectiveness, versatility, and their ability to form hydrogen bonds, facilitating hydrogel formation. In the presence of divalent metallic ions, ALG undergoes ionic crosslinking, resulting in rapid gelation. This facilitated prompt PVA-ALG film curing and allowed for immediate decontamination of targeted surfaces. Additionally, bentonite nanoclay, titanium nanoparticles, and a tetrasulfonated nickel phthalocyanine (NiPc) derivative were incorporated into the formulations to enhance absorption capacity, improve mechanical properties, and confer photocatalytic activity to the hydrogels obtained via Zn2+—mediated ionic crosslinking. The resulting hydrogels underwent characterization using a variety of analytical techniques, including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), viscometry, and mechanical analysis (shear, tensile, and compression tests), as well as swelling investigations, to establish the optimal formulations for CWA decontamination applications. The introduction of the fillers led to an increase in the maximum strain up to 0.14 MPa (maximum tensile resistance) and 0.39 MPa (maximum compressive stress). The UV-Vis characterization of the hydrogels allowed the determination of the band-gap value and absorption domain. A gas chromatography–mass spectrometry assay was employed to evaluate the decontamination efficacy for a chemical warfare agent (sulfur mustard—HD) and confirmed that the ionic crosslinked hydrogel films achieved decontamination efficiencies of up to 92.3%. Furthermore, the presence of the photocatalytic species can facilitate the degradation of up to 90% of the HD removed from the surface and entrapped inside the hydrogel matrix, which renders the post-decontamination residue significantly less dangerous.
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- 2024
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21. Transrenal Mycobacterium tuberculosis DNA in pulmonary tuberculosis patients during the first 14 days of treatment
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Irina Kontsevaya, Jan Heyckendorf, Frauke Koops, Doris Hillemann, Torsten Goldmann, Caryn M. Upton, Veronique De Jager, Andreas Diacon, and Christoph Lange
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Mycobacterium tuberculosis ,early bactericidal activity ,anti-tuberculous treatment ,Microbiology ,QR1-502 - Abstract
ABSTRACT We assessed the performance of a novel real-time PCR-based transrenal DNA (trDNA) assay for the specific detection of Mycobacterium tuberculosis as a candidate marker of the early anti-tuberculosis therapy response. The study was performed on 288 urine samples from 72 tuberculosis patients collected at baseline and days 3, 7, and 14 of treatment with amoxicillin-clavulanic acid alone or in combination with meropenem, ertapenem, optimized-dose rifampicin, or standard treatment control in South Africa. trDNA was detected in one-third of the samples. The highest proportion of positive PCR results (cycle threshold < 36) was observed on days 3 and 7, reflecting the point in time when maximum bacterial killing and disintegration are expected. When analyzed by study arms, the trend was observed in groups treated with active antibiotics affecting cell wall integrity (meropenem, control) but not in inactive drugs (ertapenem, amoxicillin/clavulanic acid alone) or active drugs not affecting the cell wall (rifampicin). Overall, however, the trDNA assay did not correlate well with sputum culture-based decline of viable bacteria. This is possibly due to trDNA reflecting the killing of both culturable and non-culturable bacteria and should be explored further. IMPORTANCE This study presents the results of the evaluation of a novel method for the detection of Mycobacterium tuberculosis, the causative agent of tuberculosis, in urine. Detecting parts of the mycobacteria in urine is of particular interest as it allows us to use a sample that is easy to obtain and that does not require uncomfortable procedures or safety precautions like obtaining sputum for culture, which is the most commonly used sample in the diagnosis of tuberculosis. In certain groups of individuals who cannot produce sputum, for example, children, non-sputum-based methods have particular importance. We found that the method tested was able to detect bacterial killing by active antibiotics that disrupt the cell wall and lead to fragmentation of bacteria. However, the assay can't detect inactive bacteria or bacteria that are active with an intact cell wall.
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- 2023
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22. Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications.
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Bisimwa, Bertin C, Nachega, Jean B, Warren, Robin M, Theron, Grant, Metcalfe, John Z, Shah, Maunank, Diacon, Andreas H, Sam-Agudu, Nadia A, Yotebieng, Marcel, Bulabula, André NH, Katoto, Patrick DMC, Chirambiza, Jean-Paul, Nyota, Rosette, Birembano, Freddy M, Musafiri, Eric M, Byadunia, Sifa, Bahizire, Esto, Kaswa, Michel K, Callens, Steven, and Kashongwe, Zacharie M
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Tuberculosis ,Infectious Diseases ,Prevention ,Clinical Research ,Rare Diseases ,Biodefense ,Emerging Infectious Diseases ,Vaccine Related ,Antimicrobial Resistance ,Infection ,Good Health and Well Being ,Adult ,Cross-Sectional Studies ,Democratic Republic of the Congo ,Humans ,Microbial Sensitivity Tests ,Mutation ,Mycobacterium tuberculosis ,Rifampin ,Sensitivity and Specificity ,Tuberculosis ,Multidrug-Resistant ,GenoType MTBDRplus assay ,drug resistance ,rpoB mutations ,inhA mutations ,DRC ,inhA mutations ,rpoB mutations ,GenoType MTBDRplus assay ,Biological Sciences ,Medical and Health Sciences ,Microbiology - Abstract
BackgroundRifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrug-resistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert MTB/RIF (Xpert)-detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC).MethodsWe conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy.ResultsAmong 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB positive. Of the 224, 43 (19.2%) were RIF monoresistant, 11 (4.9%) were INH monoresistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF and INH susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens; among these, 163 (91.1%) were TB positive and 73 (44.8%) RIF resistant. Only 45/73 (61.6%) Xpert-identified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI, 92.1-100.0) for detecting RIF resistance but a positive-predictive value of only 61.6% (95% CI, 49.5-72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively.ConclusionsIn this high-risk MDR-TB study population, Xpert had low positive-predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.
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- 2021
23. Increased bactericidal activity but dose-limiting intolerability at 50 mg·kg−1 rifampicin
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Brake, Lindsey HM te, de Jager, Veronique, Narunsky, Kim, Vanker, Naadira, Svensson, Elin M, Phillips, Patrick PJ, Gillespie, Stephen H, Heinrich, Norbert, Hoelscher, Michael, Dawson, Rodney, Diacon, Andreas H, Aarnoutse, Rob E, and Boeree, Martin J
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Clinical Trials and Supportive Activities ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,Adult ,Antitubercular Agents ,Humans ,Isoniazid ,Pyrazinamide ,Rifampin ,Tuberculosis ,Pulmonary ,PanACEA Consortium ,Medical and Health Sciences ,Respiratory System ,Cardiovascular medicine and haematology - Abstract
Accumulating data indicate that higher rifampicin doses are more effective and shorten tuberculosis (TB) treatment duration. This study evaluated the safety, tolerability, pharmacokinetics, and 7- and 14-day early bactericidal activity (EBA) of increasing doses of rifampicin. Here we report the results of the final cohorts of PanACEA HIGHRIF1, a dose escalation study in treatment-naive adult smear-positive patients with TB. Patients received, in consecutive cohorts, 40 or 50 mg·kg-1 rifampicin once daily in monotherapy (day 1-7), supplemented with standard dose isoniazid, pyrazinamide and ethambutol between days 8 and 14. In the 40 mg·kg-1 cohort (n=15), 13 patients experienced a total of 36 adverse events during monotherapy, resulting in one treatment discontinuation. In the 50 mg·kg-1 cohort (n=17), all patients experienced adverse events during monotherapy, 93 in total; 11 patients withdrew or stopped study medication. Adverse events were mostly mild/moderate and tolerability rather than safety related, i.e. gastrointestinal disorders, pruritis, hyperbilirubinaemia and jaundice. There was a more than proportional increase in the rifampicin geometric mean area under the plasma concentration-time curve from time 0 to 12 h (AUC0-24 h) for 50 mg·kg-1 compared with 40 mg·kg-1; 571 (range 320-995) versus 387 (range 201-847) mg·L-1·h, while peak exposures saw proportional increases. Protein-unbound exposure after 50 mg·kg-1 (11% (range 8-17%)) was comparable with lower rifampicin doses. Rifampicin exposures and bilirubin concentrations were correlated (Spearman's ρ=0.670 on day 3, p
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- 2021
24. Anaerobe-enriched gut microbiota predicts pro-inflammatory responses in pulmonary tuberculosis.
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Naidoo, Charissa, Nyawo, Georgina, Sulaiman, Imran, Wu, Benjamin, Turner, Carolin, Bu, Kevin, Palmer, Zaida, Li, Yonghua, Reeve, Byron, Moodley, Suventha, Jackson, Jennifer, Limberis, Jason, Diacon, Andreas, van Helden, Paul, Clemente, Jose, Warren, Robin, Noursadeghi, Mahdad, Segal, Leopoldo, and Theron, Grant
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Co-occurrence network ,Host inflammation ,Microbiome ,Tuberculosis ,Adult ,Bacteria ,Anaerobic ,Female ,Gastrointestinal Microbiome ,Humans ,Inflammasomes ,Interferons ,Male ,Signal Transduction ,Transcriptome ,Tuberculosis ,Pulmonary ,Up-Regulation - Abstract
BACKGROUND: The relationship between tuberculosis (TB), one of the leading infectious causes of death worldwide, and the microbiome, which is critical for health, is poorly understood. METHODS: To identify potential microbiome-host interactions, profiling of the oral, sputum and stool microbiota [n = 58 cases, n = 47 culture-negative symptomatic controls (SCs)] and whole blood transcriptome were done in pre-treatment presumptive pulmonary TB patients. This was a cross-sectional study. Microbiota were also characterised in close contacts of cases (CCCs, n = 73) and close contacts of SCs (CCSCs, n = 82) without active TB. FINDINGS: Cases and SCs each had similar α- and β-diversities in oral washes and sputum, however, β-diversity differed in stool (PERMANOVA p = 0•035). Cases were enriched with anaerobes in oral washes, sputum (Paludibacter, Lautropia in both) and stool (Erysipelotrichaceae, Blautia, Anaerostipes) and their stools enriched in microbial genes annotated as amino acid and carbohydrate metabolic pathways. In pairwise comparisons with their CCCs, cases had Megasphaera-enriched oral and sputum microbiota and Bifidobacterium-, Roseburia-, and Dorea-depleted stools. Compared to their CCSCs, SCs had reduced α-diversities and many differential taxa per specimen type. Cases differed transcriptionally from SCs in peripheral blood (PERMANOVA p = 0•001). A co-occurrence network analysis showed stool taxa, Erysipelotrichaceae and Blautia, to negatively co-correlate with enriched death receptor and EIF2 signalling pathways whereas Anaerostipes positively correlated with enriched interferon signalling, Nur77 signalling and inflammasome pathways; all of which are host pathways associated with disease severity. In contrast, none of the taxa enriched in SCs correlated with host pathways. INTERPRETATION: TB-specific microbial relationships were identified in oral washes, induced sputum, and stool from cases before the confounding effects of antibiotics. Specific anaerobes in cases stool predict upregulation of pro-inflammatory immunological pathways, supporting the gut microbiotas role in TB. FUNDING: European & Developing Countries Clinical Trials Partnership, South African-Medical Research Council, National Institute of Allergy and Infectious Diseases.
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- 2021
25. Effect of seven anti-tuberculosis treatment regimens on sputum microbiome: a retrospective analysis of the HIGHRIF study 2 and PanACEA MAMS-TB clinical trials
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Musisi, Emmanuel, Mtafya, Bariki, Ntinginya, Nyanda E., Heinrich, Norbert, Kibiki, Gibson S., Hoelscher, Michael, Boeree, Martin, Gillespie, Stephen, Sabiiti, Wilber, Sloan, Derek, Hoffmann, Larissa, Noreña, Ivan, Lutchmun, Wandini, Dreisbach, Julia, Demel, Petra Gross, Kelly, Andrea, Brake, Lindsey te, Svensson, Elin, Aarnoutse, Rob, Honeyborne, Isobella, Wildner, Leticia Muraro, Hunt, Robert, McHugh, Timothy D., Nunn, Andrew J, Phillips, Patrick P.J., Gong, Xue, Dawson, Rodney, Narunsky, Kim, Diacon, Andreas, de Jager, Veronique, Friedrich, Sven, Sanne, Ian, Rassool, Mohammed, Mangu, Chacha, Manyama, Christina, Sabi, Issa, Minja, Lilian T., Mhimbira, Francis, Mbeya, Benno, Sasamalo, Mohamed, Reither, Klaus, Jugheli, Levan, Sam, Noel, Semvua, Hadija, Mpagama, Stellah, Liyoyo, Alphonce, Mmbaga, Blandina T., Adegbite, Bayode Romeo, Adegnika, Ayola Akim, Grobusch, Martin Peter, Grobusch, Martin P., Kirenga, Bruce, Ssengooba, Willy, Joloba, Moses, Khosa, Celso, Massango, Isabel, Azam, Khalide, Jani, Ilesh, Nliwasa, Mariott, Twabi, Hussein Hassan, Mukoka, Madalo, Msefula, Chisomo L., Wyness, Adam, Eldirdiri, Sahar, Dombay, Evelin, Ntinginya, Nyanda E, Kibiki, Gibson S, and Gillespie, Stephen H
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- 2023
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26. Accelerometer-Based Bed Occupancy Detection for Automatic, Non-Invasive Long-Term Cough Monitoring.
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Madhurananda Pahar, Igor D. S. Miranda, Andreas H. Diacon, and Thomas Niesler
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- 2023
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27. Risk Factors for COVID-19 and Respiratory Tract Infections during the Coronavirus Pandemic
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Laurynas Mockeliunas, Rob C. van Wijk, Caryn M. Upton, Jonathan Peter, Andreas H. Diacon, and Ulrika S. H. Simonsson
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risk factors ,respiratory tract infections ,COVID-19 ,time-to-event analysis ,pharmacometrics ,Medicine - Abstract
(1) Background: Some individuals are more susceptible to developing respiratory tract infections (RTIs) or coronavirus disease (COVID-19) than others. The aim of this work was to identify risk factors for symptomatic RTIs including COVID-19 and symptomatic COVID-19 during the coronavirus pandemic by using infection incidence, participant baseline, and regional COVID-19 burden data. (2) Methods: Data from a prospective study of 1000 frontline healthcare workers randomized to Bacillus Calmette–Guérin vaccination or placebo, and followed for one year, was analyzed. Parametric time-to-event analysis was performed to identify the risk factors associated with (a) non-specific symptomatic respiratory tract infections including COVID-19 (RTIs+COVID-19) and (b) symptomatic RTIs confirmed as COVID-19 using a polymerase chain reaction or antigen test (COVID-19). (3) Results: Job description of doctor or nurse (median hazard ratio [HR] 1.541 and 95% confidence interval [CI] 1.299–1.822), the reported COVID-19 burden (median HR 1.361 and 95% CI 1.260–1.469 for 1.4 COVID-19 cases per 10,000 capita), or a BMI > 30 kg/m2 (median HR 1.238 and 95% CI 1.132–1.336 for BMI of 35.4 kg/m2) increased the probability of RTIs+COVID-19, while positive SARS-CoV-2 serology at enrollment (median HR 0.583 and 95% CI 0.449–0.764) had the opposite effect. The reported COVID-19 burden (median HR 2.372 and 95% CI 2.116–2.662 for 1.4 COVID-19 cases per 10,000 capita) and a job description of doctor or nurse (median HR 1.679 and 95% CI 1.253–2.256) increased the probability of developing COVID-19, while smoking (median HR 0.428 and 95% CI 0.284–0.648) and positive SARS-CoV-2 serology at enrollment (median HR 0.076 and 95% CI 0.026–0.212) decreased it. (4) Conclusions: Nurses and doctors with obesity had the highest probability of developing RTIs including COVID-19. Non-smoking nurses and doctors had the highest probability of developing COVID-19 specifically. The reported COVID-19 burden increased the event probability, while positive SARS-CoV-2 IgG serology at enrollment decreased the probability of RTIs including COVID-19, and COVID-19 specifically.
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- 2024
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28. State-of-the-Art Polyurea Coatings: Synthesis Aspects, Structure–Properties Relationship, and Nanocomposites for Ballistic Protection Applications
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Gabriela Toader, Aurel Diacon, Sorin Mircea Axinte, Alexandra Mocanu, and Edina Rusen
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polyurea ,composites ,ballistic protections ,step-growth polymerization ,Organic chemistry ,QD241-441 - Abstract
This review presents polyurea (PU) synthesis, the structure–properties relationship, and characterization aspects for ballistic protection applications. The synthesis of polyurea entails step-growth polymerization through the reaction of an isocyanate monomer/prepolymer and a polyamine, each component possessing a functionality of at least two. A wide range of excellent properties such as durability and high resistance against atmospheric, chemical, and biological factors has made this polymer an outstanding option for ballistic applications. Polyureas are an extraordinary case because they contain both rigid segments, which are due to the diisocyanates used and the hydrogen points formed, and a flexible zone, which is due to the chemical structure of the polyamines. These characteristics motivate their application in ballistic protection systems. Polyurea-based coatings have also demonstrated their abilities as candidates for impulsive loading applications, affording a better response of the nanocomposite-coated metal sheet at the action of a shock wave or at the impact of a projectile, by suffering lower deformations than neat metallic plates.
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- 2024
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29. Dual-Responsive Hydrogels for Mercury Ion Detection and Removal from Wastewater
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Aurel Diacon, Florin Albota, Alexandra Mocanu, Oana Brincoveanu, Alice Ionela Podaru, Traian Rotariu, Ahmad A. Ahmad, Edina Rusen, and Gabriela Toader
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hydrogels ,water treatment ,mercury ,rhodamine ,phytic acid ,IPN ,Science ,Chemistry ,QD1-999 ,Inorganic chemistry ,QD146-197 ,General. Including alchemy ,QD1-65 - Abstract
This study describes the development of a fast and cost-effective method for the detection and removal of Hg2+ ions from aqueous media, consisting of hydrogels incorporating chelating agents and a rhodamine derivative (to afford a qualitative evaluation of the heavy metal entrapment inside the 3D polymeric matrix). These hydrogels, designed for the simultaneous detection and entrapment of mercury, were obtained through the photopolymerization of 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPSA) and N-vinyl-2-pyrrolidone (NVP), utilizing N,N′-methylenebisacrylamide (MBA) as crosslinker, in the presence of polyvinyl alcohol (PVA), a rhodamine B derivative, and one of the following chelating agents: phytic acid, 1,3-diamino-2-hydroxypropane-tetraacetic acid, triethylenetetramine-hexaacetic acid, or ethylenediaminetetraacetic acid disodium salt. The rhodamine derivative had a dual purpose in this study: firstly, it was incorporated into the hydrogel to allow the qualitative evaluation of mercury entrapment through its fluorogenic switch-off abilities when sensing Hg2+ ions; secondly, it was used to quantitatively evaluate the level of residual mercury from the decontaminated aqueous solutions, via the UV-Vis technique. The ICP-MS analysis of the hydrogels also confirmed the successful entrapment of mercury inside the hydrogels and a good correlation with the UV-Vis method.
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- 2024
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30. Toxicity related to standard TB therapy for pulmonary tuberculosis and treatment outcomes in the REMoxTB study according to HIV status
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Tweed, Conor D, Crook, Angela M, Dawson, Rodney, Diacon, Andreas H, McHugh, Timothy D, Mendel, Carl M, Meredith, Sarah K, Mohapi, Lerato, Murphy, Michael E, Nunn, Andrew J, Phillips, Patrick PJ, Singh, Kasha P, Spigelman, Melvin, and Gillespie, Stephen H
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Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Clinical Trials and Supportive Activities ,Patient Safety ,Rare Diseases ,Clinical Research ,Tuberculosis ,Prevention ,Infectious Diseases ,HIV/AIDS ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Adult ,Antitubercular Agents ,Ethambutol ,Female ,HIV Seropositivity ,Humans ,Incidence ,Isoniazid ,Linear Models ,Male ,Multivariate Analysis ,Prospective Studies ,Pyrazinamide ,Rifampin ,Risk Factors ,Treatment Outcome ,Tuberculosis ,Pulmonary ,United Kingdom ,Clinical trials ,HIV ,Adverse events ,Cardiorespiratory Medicine and Haematology ,Respiratory System ,Cardiovascular medicine and haematology - Abstract
BackgroundThe phase III REMoxTB study prospectively enrolled HIV-positive (with CD4+ count > 250 cells, not on anti-retroviral therapy) and HIV-negative patients. We investigated the incidence of adverse events and cure rates according to HIV status for patients receiving standard TB therapy in the trial.MethodsForty-two HIV-positive cases were matched to 220 HIV-negative controls by age, gender, ethnicity, and trial site using coarsened exact matching. Grade 3 and 4 adverse events (AEs) were summarised by MedDRA System Organ Class. Kaplan-Meier curves for time to first grade 3 or 4 AE were constructed according to HIV status with hazard ratios calculated. Patients were considered cured if they were culture negative 18 months after commencing therapy with ≥2 consecutive negative culture results.ResultsTwenty of 42 (47.6%) HIV-positive and 34 of 220 (15.5%) HIV-negative patients experienced ≥1 grade 3 or 4 AE, respectively. The majority of these were hepatobiliary disorders that accounted for 12 of 40 (30.0%) events occurring in 6 of 42 (14.3%) HIV-positive patients and for 15 of 60 (25.0%) events occurring in 9 of 220 (4.1%) HIV-negative patients. The median time to first grade 3 or 4 AE was 54 days (IQR 15.5-59.0) for HIV-positive and 29.5 days (IQR 9.0-119.0) for HIV-negative patients, respectively. The hazard ratio for experiencing a grade 3 or 4 AE among HIV-positive patients was 3.25 (95% CI 1.87-5.66, p
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- 2019
31. Novel ZnO-biochar nanocomposites obtained by hydrothermal method in extracts of Ulva lactuca collected from Black Sea
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Dumbrava, Anca, Matei, Cristian, Diacon, Aurel, Moscalu, Florin, and Berger, Daniela
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- 2023
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32. Building sustainable clinical trial sites in Sub-Saharan Africa through networking, infrastructure improvement, training and conducting clinical studies: The PanACEA approach
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Mekota, Anna-Maria, Gillespie, Stephen H., Hoelscher, Michael, Diacon, Andreas H., Dawson, Rodney, Churchyard, Gavin, Sanne, Ian, Minja, Lilian, Kibiki, Gibson, Maboko, Leonard, Lakhi, Shabir, Joloba, Moses, Alabi, Abraham, Kirenga, Bruce, McHugh, Timothy D., Grobusch, Martin P., and Boeree, Martin J.
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- 2023
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33. Population Pharmacokinetics of Delamanid and its Main Metabolite DM-6705 in Drug-Resistant Tuberculosis Patients Receiving Delamanid Alone or Coadministered with Bedaquiline
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Tanneau, Lénaïg, Karlsson, Mats O., Diacon, Andreas H., Shenje, Justin, De Los Rios, Jorge, Wiesner, Lubbe, Upton, Caryn M., Dooley, Kelly E., Maartens, Gary, and Svensson, Elin M.
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- 2022
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34. Automatic Non-Invasive Cough Detection based on Accelerometer and Audio Signals
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Pahar, Madhurananda, Miranda, Igor, Diacon, Andreas, and Niesler, Thomas
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- 2022
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35. Wake-Cough: cough spotting and cougher identification for personalised long-term cough monitoring.
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Madhurananda Pahar, Marisa Klopper, Byron Reeve, Rob Warren 0001, Grant Theron, Andreas H. Diacon, and Thomas Niesler
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- 2022
36. INtegrating DEPrEssioN and Diabetes treatmENT (INDEPENDENT) Study (INDEPENDENT)
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National Institute of Mental Health (NIMH), University of Washington, Madras Diabetes Research Foundation, All India Institute of Medical Sciences, New Delhi, Endocrine & Diabetes Centre, Diacon Hospital, and Mohammed K Ali, MD, MSc, MBA, Associate Professor
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- 2021
37. Enhancing the light fastness of natural dyes by encapsulation in silica matrix
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Buliga, Diana-Ioana, Diacon, Aurel, Calinescu, Ioan, Popa, Ioana, Rusen, Edina, Ghebaur, Adi, Tutunaru, Oana, and Boscornea, Cristian Aurelian
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- 2022
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38. Liver toxicity associated with tuberculosis chemotherapy in the REMoxTB study
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Tweed, Conor Duncan, Wills, Genevieve Helen, Crook, Angela M, Dawson, Rodney, Diacon, Andreas H, Louw, Cheryl E, McHugh, Timothy D, Mendel, Carl, Meredith, Sarah, Mohapi, Lerato, Murphy, Michael E, Murray, Stephen, Murthy, Sara, Nunn, Andrew J, Phillips, Patrick PJ, Singh, Kasha, Spigelman, M, and Gillespie, SH
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Rare Diseases ,Liver Disease ,Tuberculosis ,Orphan Drug ,Digestive Diseases ,Infectious Diseases ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,Adolescent ,Adult ,Chemical and Drug Induced Liver Injury ,Female ,Humans ,Incidence ,Male ,Middle Aged ,Young Adult ,Hepatotoxicity ,Drug-induced liver injury ,Treatment monitoring ,Medical and Health Sciences ,General & Internal Medicine ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundDrug-induced liver injury (DILI) is a common complication of tuberculosis treatment. We utilised data from the REMoxTB clinical trial to describe the incidence of predisposing factors and the natural history in patients with liver enzyme levels elevated in response to tuberculosis treatment.MethodsPatients received either standard tuberculosis treatment (2EHRZ/4HR), or a 4-month regimen in which moxifloxacin replaced either ethambutol (isoniazid arm, 2MHRZ/2MHR) or isoniazid (ethambutol arm, 2EMRZ/2MR). Hepatic enzymes were measured at 0, 2, 4, 8, 12 and 17 weeks and as clinically indicated during reported adverse events. Patients included were those receiving at least one dose of drug and with two or more hepatic enzyme measurements.ResultsA total of 1928 patients were included (639 2EHRZ/4HR, 654 2MHRZ/2MHR and 635 2EMRZ/2MR). DILI was defined as peak alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal (5 × ULN) or ALT ≥ 3 × ULN with total bilirubin > 2 × ULN. DILI was identified in 58 of the 1928 (3.0%) patients at a median time of 28 days (interquartile range IQR 14-56). Of 639 (6.4%) patients taking standard tuberculosis therapy, 41 experienced clinically significant enzyme elevations (peak ALT ≥ 3 × ULN). On standard therapy, 21.1% of patients aged >55 years developed a peak ALT/aspartate aminotransferase (AST) ≥ 3 × ULN (p = 0.01) and 15% of HIV-positive patients experienced a peak ALT/AST ≥ 3 × ULN compared to 9% of HIV-negative patients (p = 0.160). The median peak ALT/AST was higher in isoniazid-containing regimens vs no-isoniazid regimens (p < 0.05), and lower in moxifloxacin-containing arms vs no-moxifloxacin arms (p < 0.05). Patients receiving isoniazid reached a peak ALT ≥ 3 × ULN 9.5 days earlier than those on the ethambutol arm (median time of 28 days vs 18.5 days). Of the 67 Asian patients with a peak ALT/AST ≥ 3 × ULN, 57 (85.1%) were on an isoniazid-containing regimen (p = 0.008).ConclusionsOur results provide evidence of the risk of DILI in tuberculosis patients on standard treatment. Older patients on standard therapy, HIV-positive patients, Asian patients and those receiving isoniazid were at higher risk of elevated enzyme levels. Monitoring hepatic enzymes during the first 2 months of standard therapy detected approximately 75% of patients with a peak enzyme elevation ≥3 × ULN, suggesting this should be a standard of care. These results provide evidence for the potential of moxifloxacin in hepatic sparing.
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- 2018
39. Toxicity associated with tuberculosis chemotherapy in the REMoxTB study
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Tweed, Conor D, Crook, Angela M, Amukoye, Evans I, Dawson, Rodney, Diacon, Andreas H, Hanekom, Madeline, McHugh, Timothy D, Mendel, Carl M, Meredith, Sarah K, Murphy, Michael E, Murthy, Saraswathi E, Nunn, Andrew J, Phillips, Patrick PJ, Singh, Kasha P, Spigelman, Melvin, Wills, Genevieve H, and Gillespie, Stephen H
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Biomedical and Clinical Sciences ,Clinical Sciences ,Rare Diseases ,Infectious Diseases ,HIV/AIDS ,Orphan Drug ,Patient Safety ,Clinical Research ,Clinical Trials and Supportive Activities ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,Adult ,Antitubercular Agents ,Clinical Protocols ,Ethambutol ,Female ,HIV Seropositivity ,Humans ,Incidence ,Isoniazid ,Male ,Moxifloxacin ,Treatment Outcome ,Tuberculosis ,Pulmonary ,Tuberculosis ,Toxicity ,Clinical trials ,Adverse events ,Microbiology ,Medical Microbiology ,Clinical sciences ,Medical microbiology ,Public health - Abstract
BackgroundThe incidence and severity of tuberculosis chemotherapy toxicity is poorly characterised. We used data available from patients in the REMoxTB trial to provide an assessment of the risks associated with the standard regimen and two experimental regimens containing moxifloxacin.MethodsAll grade 3 & 4 adverse events (AEs) and their relationship to treatment for patients who had taken at least one dose of therapy in the REMoxTB clinical trial were recorded. Univariable logistic regression was used to test the relationship of baseline characteristics to the incidence of grade 3 & 4 AEs and significant characteristics (p
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- 2018
40. E7 nematic liquid crystal encapsulated in a polymeric photonic crystal
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Rusen, Edina, Diacon, Aurel, Mitran, Raul-Augustin, Dinescu, Adrian, Nistor, Cristina, Șomoghi, Raluca, Cristian Boscornea, Aurelian, and Mănăilă-Maximean, Doina
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- 2022
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41. Safety and efficacy of BCG re-vaccination in relation to COVID-19 morbidity in healthcare workers: A double-blind, randomised, controlled, phase 3 trial
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Upton, Caryn M., van Wijk, Rob C., Mockeliunas, Laurynas, Simonsson, Ulrika S.H., McHarry, Kirsten, van den Hoogen, Gerben, Muller, Chantal, von Delft, Arne, van der Westhuizen, Helene-Mari, van Crevel, Reinout, Walzl, Gerhard, Baptista, Pedro M., Peter, Jonathan, and Diacon, Andreas H.
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- 2022
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42. On the ultrasound-assisted preparation of Cu/SiO2 system as a selective catalyst for the conversion of biobutanol to butanal
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Chisega-Negrilă, Ciprian-Gabriel, Diacon, Aurel, Călinescu, Ioan, Vînătoru, Mircea, Berger, Daniela, Matei, Cristian, and Vasilievici, Gabriel
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- 2022
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43. Automatic Non-Invasive Cough Detection based on Accelerometer and Audio Signals.
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Madhurananda Pahar, Igor D. S. Miranda, Andreas H. Diacon, and Thomas Niesler
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- 2022
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44. Sputum lipoarabinomannan (LAM) as a biomarker to determine sputum mycobacterial load: exploratory and model-based analyses of integrated data from four cohorts
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Jones, Aksana, Saini, Jay, Kriel, Belinda, Via, Laura E., Cai, Yin, Allies, Devon, Hanna, Debra, Hermann, David, Loxton, Andre G., Walzl, Gerhard, Diacon, Andreas H., Romero, Klaus, Higashiyama, Ryo, Liu, Yongge, and Berg, Alexander
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- 2022
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45. High rifampicin peak plasma concentrations accelerate the slow phase of bacterial decline in tuberculosis patients: Evidence for heteroresistance.
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Antal Martinecz, Martin J. Boeree, Andreas H. Diacon, Rodney Dawson, Colin Hemez, Rob E. Aarnoutse, and Pia Abel zur Wiesch
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- 2023
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46. Sputum lipoarabinomannan (LAM) as a biomarker to determine sputum mycobacterial load: exploratory and model-based analyses of integrated data from four cohorts
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Aksana Jones, Jay Saini, Belinda Kriel, Laura E. Via, Yin Cai, Devon Allies, Debra Hanna, David Hermann, Andre G. Loxton, Gerhard Walzl, Andreas H. Diacon, Klaus Romero, Ryo Higashiyama, Yongge Liu, and Alexander Berg
- Subjects
Tuberculosis ,Lipoarabinomannan ,LAM ,Biomarker ,Mycobacterium ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Despite the high global disease burden of tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb) infection, novel treatments remain an urgent medical need. Development efforts continue to be hampered by the reliance on culture-based methods, which often take weeks to obtain due to the slow growth rate of Mtb. The availability of a “real-time” measure of treatment efficacy could accelerate TB drug development. Sputum lipoarabinomannan (LAM; an Mtb cell wall glycolipid) has promise as a pharmacodynamic biomarker of mycobacterial sputum load. Methods The present analysis evaluates LAM as a surrogate for Mtb burden in the sputum samples from 4 cohorts of a total of 776 participants. These include those from 2 cohorts of 558 non-TB and TB participants prior to the initiation of treatment (558 sputum samples), 1 cohort of 178 TB patients under a 14-day bactericidal activity trial with various mono- or multi-TB drug therapies, and 1 cohort of 40 TB patients with data from the first 56-day treatment of a standard 4-drug regimen. Results Regression analysis demonstrated that LAM was a predictor of colony-forming unit (CFU)/mL values obtained from the 14-day treatment cohort, with well-estimated model parameters (relative standard error ≤ 22.2%). Moreover, no changes in the relationship between LAM and CFU/mL were observed across the different treatments, suggesting that sputum LAM can be used to reasonably estimate the CFU/mL in the presence of treatment. The integrated analysis showed that sputum LAM also appears to be as good a predictor of time to Mycobacteria Growth Incubator Tube (MGIT) positivity as CFU/mL. As a binary readout, sputum LAM positivity is a strong predictor of solid media or MGIT culture positivity with an area-under-the-curve value of 0.979 and 0.976, respectively, from receiver-operator curve analysis. Conclusions Our results indicate that sputum LAM performs as a pharmacodynamic biomarker for rapid measurement of Mtb burden in sputum, and thereby may enable more efficient early phase clinical trial designs (e.g., adaptive designs) to compare candidate anti-TB regimens and streamline dose selection for use in pivotal trials. Trial registration NexGen EBA study (NCT02371681)
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- 2022
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47. Effectiveness of the Ad26.COV2.S vaccine in health-care workers in South Africa (the Sisonke study): results from a single-arm, open-label, phase 3B, implementation study
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Brumskine, William, Naicker, Nivashnee, Makhaza, Disebo, Naicker, Vimla, Naidoo, Logashvari, Spooner, Elizabeth, van Nieuwenhuizen, Elane, Mngadi, Kathryn, Nchabeleng, Maphoshane, Innes, James Craig, Gill, Katherine, Petrick, Friedrich Georg, Barnabas, Shaun, Badal-Faesen, Sharlaa, Kassim, Sheetal, Mahoney, Scott Hayden, Lazarus, Erica, Nana, Anusha, Maboa, Rebone Molobane, Kotze, Philip, Lombaard, Johan, Malan, Daniel Rudolf, Kotze, Sheena, Mohlala, Phuthi, Ward, Amy, Meintjes, Graeme, Urbach, Dorothea, Patel, Faeezah, Diacon, Andreas, Ahmed, Khatija, Grobbelaar, Coert, Mda, Pamela, Dubula, Thozama, Luabeya, Angelique, Mamba, Musawenkosi Bhekithemba, Burgess, Lesley, Dawson, Rodney, Bekker, Linda-Gail, Garrett, Nigel, Goga, Ameena, Fairall, Lara, Reddy, Tarylee, Yende-Zuma, Nonhlanhla, Kassanjee, Reshma, Collie, Shirley, Sanne, Ian, Boulle, Andrew, Seocharan, Ishen, Engelbrecht, Imke, Davies, Mary-Ann, Champion, Jared, Chen, Tommy, Bennett, Sarah, Mametja, Selaelo, Semenya, Mabatlo, Moultrie, Harry, de Oliveira, Tulio, Lessells, Richard John, Cohen, Cheryl, Jassat, Waasila, Groome, Michelle, Von Gottberg, Anne, Le Roux, Engelbert, Khuto, Kentse, Barouch, Dan, Mahomed, Hassan, Wolmarans, Milani, Rousseau, Petro, Bradshaw, Debbie, Mulder, Michelle, Opie, Jessica, Louw, Vernon, Jacobson, Barry, Rowji, Pradeep, Peter, Jonny G, Takalani, Azwi, Odhiambo, Jackline, Mayat, Fatima, Takuva, Simbarashe, Corey, Lawrence, and Gray, Glenda E
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- 2022
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48. MXenes and polymeric colloids nanocomposites for EMI shielding.
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Rusen, Edina, Mocanu, Alexandra, Brincoveanu, Oana, Boldeiu, Adina, Romanitan, Cosmin, Aldrigo, Martino, Iordănescu, Sergiu, Diacon, Aurel, Toader, Gabriela, and Gavrila, Raluca
- Abstract
This study presents the synthesis and characterization of nanocomposites based on polymer colloids (PC) and MXenes for applications in EMI shielding. The PCs were synthesized in the presence of MXenes by soap-free emulsion polymerization. The presence of the MXenes during the polymerization process induces changes in the nucleation process, which also occurs between the MXenes layers, leading to intercalated and finally fully exfoliated structures arising from the polymerization progress. Two co-monomer systems were synthesized in the presence of MXenes, both based on styrene (ST) and a second monomer, with different hydrophilic characteristics acrylic acid (AA) and hydroxypropyl methacrylate (HPMA), respectively. The nanocomposites were characterized by SEM, DLS, XRD, TGA, and EMI shielding capacity analyses. The analyses confirmed better compatibility between HPMA and the MXenes, which facilitated the formation of an exfoliated structure. The polymer colloids were incorporated into an epoxy resin to evaluate their EMI shielding abilities. The EMI tests showed that the electromagnetic properties of the epoxy film varied depending on the concentration of ST-HPMA-MXenes, resulting in increased electromagnetic transparency or absorption capacity. [ABSTRACT FROM AUTHOR]
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- 2024
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49. Experimental Investigations on Shear Thickening Fluids as "Liquid Body Armors": Non-Conventional Formulations for Ballistic Protection.
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Alexe, Florentina, Sau, Ciprian, Iorga, Ovidiu, Toader, Gabriela, Diacon, Aurel, Rusen, Edina, Lazaroaie, Claudiu, Ginghina, Raluca Elena, Tiganescu, Tudor Viorel, Teodorescu, Mircea, and Sobetkii, Arcadie
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POLYMER solutions ,IMPACT testing ,COMPOSITE structures ,POLYPROPYLENE oxide ,BODY armor - Abstract
Shear thickening fluids (STFs) have garnered attention as potential enhancers of protective capabilities and for the optimization of Kevlar
® armor design. To assess the possible shear thickening properties and potential application in ballistic protection, ten formulations were developed by employing polyethylene glycol (PEG) or polypropylene glycol (PPG), along with fumed silica or Aerosil HDK® . Rheological characterization facilitated the identification of formulations displaying shear thickening behavior. The potential integration of the selected shear thickening fluids (STFs) into Kevlar® -based composites was investigated by studying the impact resistance of Kevlar® soft armor structures. Also, high-velocity impact testing revealed that the distance between aramid layers plays a crucial role in the impact resistance effectiveness of Kevlar® –STF composite structures and that there is a very narrow domain between optimal and undesired scenarios in which STF could facilitate the penetration of Kevlar. The introduction of STF between the Kevlar sheets disrupted this packing and the energy absorption capacity of the material was not improved. Only one formulation (PEG400, Aerosil 27 wt.%) led to a less profound traumatic imprint and stopped the bullet when it was placed between layers no.1 and no.2 from a total of 11 layers of Kevlar XP. These experimental findings align with the modeling and simulation of Kevlar® –STF composites using Ansys simulation software (Ansys® AutoDyn 2022 R2). [ABSTRACT FROM AUTHOR]- Published
- 2024
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50. High-Dose Isoniazid Lacks EARLY Bactericidal Activity against Isoniazid-resistant Tuberculosis Mediated by katG Mutations: A Randomized Phase II Clinical Trial.
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Gausi, Kamunkhwala, Ignatius, Elisa H., De Jager, Veronique, Upton, Caryn, Kim, Soyeon, McKhann, Ashley, Moran, Laura, Wiesner, Lubbe, von Groote-Bidlingmaier, Florian, Marzinek, Philip, Vanker, Naadira, Yvetot, Joseph, Pierre, Samuel, Rosenkranz, Susan L., Swindells, Susan, Diacon, Andreas H., Nuermberger, Eric L., Denti, Paolo, and Dooley, Kelly E.
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ISONIAZID ,MULTIDRUG-resistant tuberculosis ,TUBERCULOSIS ,CLINICAL trials ,BACTERICIDAL action ,MYCOBACTERIUM tuberculosis - Abstract
Rationale: Observational studies suggest that high-dose isoniazid may be efficacious in treating multidrug-resistant tuberculosis. However, its activity against Mycobacterium tuberculosis (M.tb) with katG mutations (which typically confer high-level resistance) is not established. Objectives: To characterize the early bactericidal activity (EBA) of high-dose isoniazid in patients with tuberculosis caused by katG-mutated M.tb. Methods: A5312 was a phase IIA randomized, open-label trial. Participants with tuberculosis caused by katG-mutated M.tb were randomized to receive 15 or 20 mg/kg isoniazid daily for 7 days. Daily sputum samples were collected for quantitative culture. Intensive pharmacokinetic sampling was performed on Day 6. Data were pooled across all A5312 participants for analysis (drug-sensitive, inhA-mutated, and katG-mutated M.tb). EBA was determined using nonlinear mixed-effects modeling. Measurements and Main Results: Of 80 treated participants, 21 had katG-mutated M.tb. Isoniazid pharmacokinetics were best described by a two-compartment model with an effect of NAT2 acetylator phenotype on clearance. Model-derived maximum concentration and area under the concentration–time curve in the 15 and 20 mg/kg groups were 15.0 and 22.1 mg/L and 57.6 and 76.8 mg ⋅ h/L, respectively. Isoniazid bacterial kill was described using an effect compartment and a sigmoidal maximum efficacy relationship. Isoniazid potency against katG-mutated M.tb was approximately 10-fold lower than in inhA-mutated M.tb. The highest dose of 20 mg/kg did not demonstrate measurable EBA, except against a subset of slow NAT2 acetylators (who experienced the highest concentrations). There were no grade 3 or higher drug-related adverse events. Conclusions: This study found negligible bactericidal activity of high-dose isoniazid (15–20 mg/kg) in the majority of participants with tuberculosis caused by katG-mutated M.tb. Clinical trial registered with (NCT01936831). [ABSTRACT FROM AUTHOR]
- Published
- 2024
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