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2. RAD51C-XRCC3 structure and cancer patient mutations define DNA replication roles

Author

Longo, Michael A, Roy, Sunetra, Chen, Yue, Tomaszowski, Karl-Heinz, Arvai, Andrew S, Pepper, Jordan T, Boisvert, Rebecca A, Kunnimalaiyaan, Selvi, Keshvani, Caezanne, Schild, David, Bacolla, Albino, Williams, Gareth J, Tainer, John A, and Schlacher, Katharina

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Physical Sciences, Oncology and Carcinogenesis, Genetics, Breast Cancer, Cancer, Ovarian Cancer, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Male, Humans, Prostatic Neoplasms, Rad51 Recombinase, Mutation, DNA Replication, Adenosine Triphosphate, DNA-Binding Proteins
Abstract

RAD51C is an enigmatic predisposition gene for breast, ovarian, and prostate cancer. Currently, missing structural and related functional understanding limits patient mutation interpretation to homology-directed repair (HDR) function analysis. Here we report the RAD51C-XRCC3 (CX3) X-ray co-crystal structure with bound ATP analog and define separable RAD51C replication stability roles informed by its three-dimensional structure, assembly, and unappreciated polymerization motif. Mapping of cancer patient mutations as a functional guide confirms ATP-binding matching RAD51 recombinase, yet highlights distinct CX3 interfaces. Analyses of CRISPR/Cas9-edited human cells with RAD51C mutations combined with single-molecule, single-cell and biophysics measurements uncover discrete CX3 regions for DNA replication fork protection, restart and reversal, accomplished by separable functions in DNA binding and implied 5' RAD51 filament capping. Collective findings establish CX3 as a cancer-relevant replication stress response complex, show how HDR-proficient variants could contribute to tumor development, and identify regions to aid functional testing and classification of cancer mutations.

Published
2023

4. Recent developments in biosensing methods for extracellular vesicle protein characterization

Author

Suthar, Jugal, Taub, Marissa, Carney, Randy P, Williams, Gareth R, and Guldin, Stefan

Subjects
Prevention, Bioengineering, Biotechnology, Nanotechnology, Generic health relevance, Humans, Exosomes, Extracellular Vesicles, Biomarkers, Biosensing Techniques, absorbance, acoustic resonators, biosensing, electrochemical, electrochemical quartz crystal microbalance with dissipation, exosomes, extracellular vesicles, fluorescence, interferometry, plasmon resonance, surface enhanced Raman spectroscopy, Medicinal and Biomolecular Chemistry, Biomedical Engineering, Nanoscience & Nanotechnology
Abstract

Research into extracellular vesicles (EVs) has grown significantly over the last few decades with EVs being widely regarded as a source of biomarkers for human health and disease with massive clinical potential. Secreted by every cell type in the body, EVs report on the internal cellular conditions across all tissue types. Their presence in readily accessible biofluids makes the potential of EV biosensing highly attractive as a noninvasive diagnostic platform via liquid biopsies. However, their small size (50-250 nm), inherent heterogeneity, and the complexity of the native biofluids introduce challenges for effective characterization, thus, limiting their clinical utility. This has led to a surge in the development of various novel EV biosensing techniques, with capabilities beyond those of conventional methods that have been directly transferred from cell biology. In this review, key detection principles used for EV biosensing are summarized, with a focus on some of the most recent and fundamental developments in the field over the last 5 years. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > In Vitro Nanoparticle-Based Sensing.

Published
2023

6. 'It's about Portraying That We Are Organised …' A Case Study Looking at Understanding Identity Changes within One Free School's Physical Education and School Sport (Pess) Programme

Author

Williams, Gareth, Burrows, Adam, and Williams, Dean

Abstract

This research looked at the management of identity change within Physical Education and School Sport (PESS) at one of the first Free schools in England. Opened as a new institution within an unfamiliar setting, the school had to contend with limited resources for an ambitious programme based upon a full complement of examination courses and an emphasis on prestigious team sports using a traditional public-school model. A single case study methodology revealed that subsequent changes in identity stemmed from staffing issues, alongside a shift in personal philosophies towards a more inclusive ideology. Both senior management and middle management agreed that PESS needed to offer more sports to more pupils while still contributing towards the school's "knowledge rich" achievement-based ethos. Using Goffman's concept of "impression management", changes are explained by the analysis of a team "performance" communication to parents, identified by interviewees as key policy actors in the life of the school. This approach has been successful in justifying change, a finding that will help to understand the extent to which parental expectations are managed at Free schools. However, elements of traditionalism remain within the school's games-based PESS programme and possibilities for innovation are interpreted by policy actors as necessitating changes in content rather than within pedagogy or curriculum design. Recommendations for future study include the need to fully understand the freedoms associated with Free schools, particularly expectations for curriculum innovation.

Published
2023
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7. Deep Learning-Assisted Co-registration of Full-Spectral Autofluorescence Lifetime Microscopic Images with H&E-Stained Histology Images

Author

Wang, Qiang, Fernandes, Susan, Williams, Gareth O. S., Finlayson, Neil, Akram, Ahsan R., Dhaliwal, Kevin, Hopgood, James R., and Vallejo, Marta

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition, Quantitative Biology - Quantitative Methods
Abstract

Autofluorescence lifetime images reveal unique characteristics of endogenous fluorescence in biological samples. Comprehensive understanding and clinical diagnosis rely on co-registration with the gold standard, histology images, which is extremely challenging due to the difference of both images. Here, we show an unsupervised image-to-image translation network that significantly improves the success of the co-registration using a conventional optimisation-based regression network, applicable to autofluorescence lifetime images at different emission wavelengths. A preliminary blind comparison by experienced researchers shows the superiority of our method on co-registration. The results also indicate that the approach is applicable to various image formats, like fluorescence intensity images. With the registration, stitching outcomes illustrate the distinct differences of the spectral lifetime across an unstained tissue, enabling macro-level rapid visual identification of lung cancer and cellular-level characterisation of cell variants and common types. The approach could be effortlessly extended to lifetime images beyond this range and other staining technologies., Comment: 21 pages, 9 figures, 5 equations, 1 table

Published
2022

8. Coral reefs benefit from reduced land–sea impacts under ocean warming

Author

Gove, Jamison M., Williams, Gareth J., Lecky, Joey, Brown, Eric, Conklin, Eric, Counsell, Chelsie, Davis, Gerald, Donovan, Mary K., Falinski, Kim, Kramer, Lindsey, Kozar, Kelly, Li, Ning, Maynard, Jeffrey A., McCutcheon, Amanda, McKenna, Sheila A., Neilson, Brian J., Safaie, Aryan, Teague, Christopher, Whittier, Robert, and Asner, Gregory P.

Published
2023
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12. Orthographic Knowledge and Clue Word Facilitated Spelling in Children with Developmental Language Disorder

Author

Williams, Gareth J., Larkin, Rebecca F., Rose, Naomi V., Whitaker, Emily, Roeser, Jens, and Wood, Clare

Abstract

Purpose: This study investigated the orthographic knowledge and how orthographic and phonological information could support children with developmental language disorder (DLD) to make more accurate spelling attempts. Method: Children with DLD (N = 37) were matched with chronological age-matched (CAM) children and language age-matched children. These children completed specific and general orthographic knowledge tasks as well as spelling task conditions with either no clue word (pretest), a phonological clue word, or an orthographic clue word. Results: Children with DLD were significantly less accurate in their specific orthographic knowledge, compared with CAM children, but had similar scores for general orthographic knowledge to CAM children. Children with DLD and both controls had significantly higher spelling scores in the orthographic clue word condition compared with a pretest pseudoword spelling task. Conclusions: Children with DLD acquire the general knowledge of a written language's orthography but, possibly through less print exposure, have less well-represented word-specific orthographic knowledge. Moreover, children with DLD are able to extract the orthographic features of a clue word and employ these to produce more accurate spellings. These findings offer support for a spelling intervention approach based on orthography.

Published
2021
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14. Borrowing information across patient subgroups in clinical trials, with application to a paediatric trial

Author

Turner, Rebecca M., Turkova, Anna, Moore, Cecilia L., Bamford, Alasdair, Archary, Moherndran, Barlow-Mosha, Linda N., Cotton, Mark F., Cressey, Tim R., Kaudha, Elizabeth, Lugemwa, Abbas, Lyall, Hermione, Mujuru, Hilda A., Mulenga, Veronica, Musiime, Victor, Rojo, Pablo, Tudor-Williams, Gareth, Welch, Steven B., Gibb, Diana M., Ford, Deborah, and White, Ian R.

Published
2022
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15. Ternary NiCoTi-layered double hydroxide nanosheets as a pH-responsive nanoagent for photodynamic/chemodynamic synergistic therapy

Author

Hu, Tingting, Zhou, Zhan, Zha, Jiajia, Williams, Gareth R., Wu, Zhikang, Zhao, Wei, Shen, Weicheng, Li, Hai, Weng, Xisheng, Liang, Ruizheng, and Tan, Chaoliang

Abstract

Combining photodynamic therapy (PDT) with chemodynamic therapy (CDT) has been proven to be a promising strategy to improve the treatment efficiency of cancer, because of the synergistic therapeutic effect arising between the two modalities. Herein, we report an inorganic nanoagent based on ternary NiCoTi-layered double hydroxide (NiCoTi-LDH) nanosheets to realize highly efficient photodynamic/chemodynamic synergistic therapy. The NiCoTi-LDH nanosheets exhibit oxygen vacancy-promoted electron-hole separation and photogenerated hole-induced O2-independent reactive oxygen species (ROS) generation under acidic circumstances, realizing in situpH-responsive PDT. Moreover, due to the effective conversion between Co3+and Co2+caused by photogenerated electrons, the NiCoTi-LDH nanosheets catalyze the release of hydroxyl radicals (·OH) from H2O2through Fenton reactions, resulting in CDT. Laser irradiation enhances the catalyzed ability of the NiCoTi-LDH nanosheets to promote the ROS generation, resulting in a better performance than TiO2nanoparticles at pH 6.5. In vitroand in vivoexperimental results show conclusively that NiCoTi-LDH nanosheets plus irradiation lead to efficient cell apoptosis and significant inhibition of tumor growth. This study reports a new pH-responsive inorganic nanoagent with oxygen vacancy-promoted photodynamic/chemodynamic synergistic performance, offering a potentially appealing clinical strategy for selective tumor elimination.

Published
2024
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18. Impact of the iWHELD digital person‐centered care program on quality of life, agitation and psychotropic medications in people with dementia living in nursing homes during the COVID‐19 pandemic: A randomized controlled trial.

Author

McDermid, Joanne, Henley, William, Corbett, Anne, Williams, Gareth, Fossey, Jane, Clare, Linda, Fox, Chris, Aarsland, Dag, Khan, Zunera, Soto, Maria, Woodward‐Carlton, Barbara, Cook, Esme Moniz, Cummings, Jeffrey, Sweetnam, Adrienne, Chan, Xavier, Lawrence, Megan, and Ballard, Clive

Abstract

INTRODUCTION: iWHELD is a digital person‐centered care program for people with dementia in nursing homes adapted for remote delivery during the COVID‐19 pandemic. METHODS: A 16‐week two‐arm cluster‐randomized controlled trial in 149 UK nursing homes compared iWHELD with treatment as usual (TAU). Primary outcome was the overall quality of life with secondary outcomes of agitation and psychotropic use. RESULTS: iWHELD conferred benefit to quality of life on the primary (F = 4.3, p = 0.04) and secondary measures of quality of life (F = 6.45, p = 0.01) and reduced psychotropic medication use (χ2 = 4.08, p = 0.04) with no worsening of agitation. Benefit was seen in participants who contracted COVID‐19, those with agitation at baseline, and those taking psychotropic medications. DISCUSSION: iWHELD confers benefits to quality of life and key measures of well‐being, can be delivered during the challenging conditions of a pandemic, and should be considered for use alongside any emerging pharmacological treatment for neuropsychiatric symptoms. Highlights: iWHELD is the only remote, digital delivery nursing home training programme for dementia careiWHELD improved quality of life in people with dementia and reduced antipsychotic use without worsening of agitationResidents who contracted Covid‐19 during the study also experienced benefits from iWHELDiWHELD offers a valuable, pandemic‐safe tool for improving dementia care [ABSTRACT FROM AUTHOR]

Published
2024
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19. A Roman Hoard Unearthed.

Author

Williams, Gareth

Abstract

In this article titled "A Roman Hoard Unearthed," the author recounts their experience of discovering a hoard of Roman coins while metal detecting in Llangorse, Brecon. The author and their friends found a total of twenty coins, including denarii of various emperors and empresses such as Trajan, Aelius Caesar, Antoninus Pius, Faustina Senior, Marcus Aurelius, Faustina Junior, and Lucilla. The hoard has not been officially assessed yet, but it is estimated to have been deposited around AD 170 onwards. The author also mentions finding additional coins during a return visit, potentially increasing the date spread to around 100 years. The discovery of these coins provided an unforgettable thrill for the author and their friends. [Extracted from the article]

Published
2024

21. Fabrication of Electrospun Levodopa-Carbidopa Fixed-Dose Combinations

Author

Bukhary, Haitham, Williams, Gareth R., and Orlu, Mine

Abstract

Abstract: We report in this work coaxial electrospun fibers with potential applications in the treatment of Parkinson’s disease. The fibers comprise a fixed dose combination (FDC) containing the active ingredients levodopa and carbidopa, loaded in a fast dissolving polyvinylpyrrolidone (PVP) shell and an insoluble but swellable Eudragit®RLPO core. Under appropriate processing conditions we are able to prepare fibers with distinct core/shell architectures and diameters of approximately 400 nm. X-ray diffraction and differential scanning calorimetry analyses revealed that the drugs are dispersed on the molecular level within the polymer carriers, and IR spectroscopy indicated the presence of intermolecular interactions. At pH 1, the composite fibers yields extended release over more than 8 h, with an initial loading dose being freed from the PVP shell and then a sustained release phase following from the insoluble core. This is markedly extended over the release period of the commercial FDC product, and thus the fibers generated here have the potential to be used to reduce the required dosing frequency. Graphic Abstract:

Published
2024
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22. A Novel Fit-Flexible Fluorescence Soft Imager: Tri-Sensing of Intensity, Fall-Time, and Life Profile

Author

Taimori, Ali, Mills, Bethany, Gaughan, Erin, Ali, Aysha, Dhaliwal, Kevin, Williams, Gareth, Finlayson, Neil, and Hopgood, James R.

Abstract

Time-resolved fluorescence imaging techniques, like confocal fluorescence lifetime imaging microscopy, are powerful photonic instrumentation tools of modern science with diverse applications, including: biology, medicine, and chemistry. However, complexities of the systems, both at specimen and device levels, cause difficulties in quantifying soft biomarkers. To address the problems, we first aim to understand and model the underlying photophysics of fluorescence decay curves. For this purpose, we provide a set of mathematical functions, called “life models”, fittable with the real temporal recordings of histogram of photon counts. For each model, an equivalent electrical circuit, called a “life circuit”, is derived for explaining the whole process. In confocal endomicroscopy, the components of excitation laser, specimen, and fluorescence-emission signal as the histogram of photon counts are modelled by a power source, network of resistor-inductor-capacitor circuitry, and multimetre, respectively. We then design a novel pixel-level temporal classification algorithm, called a “fit-flexible approach”, where qualities of “intensity”, “fall-time”, and “life profile” are identified for each point. A model selection mechanism is used at each pixel to flexibly choose the best representative life model based on a proposed Misfit-percent metric. A two-dimensional arrangement of the quantified information detects some kind of structural information. This approach showed a potential of separating microbeads from lung tissue, distinguishing the tri-sensing from conventional methods. We alleviated by 7% the error of the Misfit-percent for recovering the histograms on real samples than the best state-of-the-art competitor. Codes are available online.

Published
2024
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23. Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

Author

Turkova, Anna, White, Ellen, Kekitiinwa, Adeodata R, Mumbiro, Vivian, Kaudha, Elizabeth, Liberty, Afaaf, Ahimbisibwe, Grace Miriam, Moloantoa, Tumelo, Srirompotong, Ussanee, Mosia, Nozibusiso Rejoice, Puthanakit, Thanyawee, Kobbe, Robin, Fortuny, Clàudia, Kataike, Hajira, Bbuye, Dickson, Na-Rajsima, Sathaporn, Coelho, Alexandra, Lugemwa, Abbas, Bwakura-Dangarembizi, Mutsa F, Klein, Nigel, Mujuru, Hilda A, Kityo, Cissy, Cotton, Mark F, Ferrand, Rashida A, Giaquinto, Carlo, Rojo, Pablo, Violari, Avy, Gibb, Diana M, Ford, Deborah, Mehar (nee Abdulla), Amina Farhana, Abraham, Pattamukkil, Abrams, Elaine, Acero, Judith, Agaba, Gerald Muzorah, Ahimbisibwe, Grace, Ainebyoona, Barbara, Akobye, Winnie, Akhalwaya, Yasmeen, Akoojee, Nazim, Ali, Shabinah S., Amuge, Pauline, Andrea, Catherine, Muñoz Fernandez, Maria Angeles, Ankunda, Rogers, Rutebarika, Diana Antonia, Anugulruengkitt, Suvaporn, Apollo, Tsitsi, Archary, Moherndran, Arendze, Ronelle, Ategeka, Juliet, Atim, Eunice, Atwine, Lorna, Babiker, Abdel, Babirye, Sarah, Babu, Enock, Bagirigomwa, Edward, Baita, Angella, Balamusani, David, Baliram, Patsy, Baliruno, David, Ball, Colin, Balwa, Henry, Bamford, Alasdair, Bandi, Srini, Barker, Dominique, Barlow-Mosha, Linda, Bbuye, Dickson, Begum, Shazia, Behuhuma, Osee, Bernays, Sarah, Besigye, Rogers, Bester, Maria, Bhiri, Joyline, Bilardi, Davide, Bird, Kristien, Bollen, Pauline, Borg, Chiara, Borges Da Silva, Anne-Marie, Brown, Jackie, Bruno, Elena, Bunupuradah, Torsak, Burger, David, Buthelezi, Nomzamo, Bwakura-Dangarembizi, Mutsa, Byaruhanga, Africanus, Calvert, Joanna, Casey, Petronelle, Cassim, Haseena, Cebekhulu, Sphiwee, Chailert, Sanuphong, Chalermpantmetagul, Suwalai, Chamjamrat, Wanna, Chan, Man, Chandiwana, Precious, Chankun, Thannapat, Chanthaburanun, Sararut, Chanto, Nuttawut, Chidziva, Ennie, Chikowore, Minenhle, Chimanzi, Joy, Chinwong, Dujrudee, Chitongo, Stuart, Chitsamatanga, Moses, Choga, Joshua, Chutima, Duangrat, Clayden, Polly, Coelho, Alexandra, Colbers, Angela, Compagnucci, Alexandra, Constança Mendes, Ana, Conway, Magda, Cotton, Mark F, Crawley, Jane, Cressey, Tim R, Crisp, Jacky, Matos, Ana Cristina, Dadan, Sumaya, Daglish, Jacqui, Danaviah, Siva, Daniel, Tseleng, De Rossi, Anita, Denjanta, Sukanda, Dobbels, Els, Dowie, Maria, Dube, Prosper, Dube, Benedictor, Dudakia, Nimisha, Elwana, Alice, Epalza, Cristina, Eram, David, Erasmus, Juan, Erim, Peter, Escosa Garcia, Luis, Essack, Zaakirah, Estepa, Carolina, Etima, Monica, Fernandes, Alexandre, Fernandez, Maite, Fitzgerald, Felicity, Flynn, Jacquie, Ford, Deborah, Fortuny Guasch, Claudia, Foster, Caroline, Fourie, George, Fourie, Yolandie, Foxall, Sophie, Frank, Derusha, Gandhi, Kate, Garcia, India, Gartner, Kathleen, Gasa, Joshua, Gasa, Gugu, Giaquinto, Carlo, Gibb, Diana M, Gomez Rico, Coral, Gomez-Pena, Daniel, Gondo, Secrecy, Goodman, Anna, Gorreti Nakalema, Maria, Gozhora, Winnie, Greetanukroh, Pisut, Gregorio Maranon, Biobanco, Grossele, Tiziana, Gwande, Shamiso, Gwaze, Tapiwa, Gwenzi, Tsitsi, Hakim, James, Hakiza, Emmanuel, Kaka, Abdul Hamid, Harley, Ashley, Isaacs, Mornay, Isabirye, Richard, Ishemunyoro, Wilber, Jacobs, Tom, Jafta, Lungile, Jamil, Nasir, Janse van Rensburg, Anita Janse, Jeaven, Vinesh, Mellado Peña, Maria José, Jourdain, Gonzague, Juliet, Katabalwa, Jumpimai, Thidarat, Junkaew, Raungwit, Jupimai, Thidarat, Kaahwa, Winfred, Kabasonga, Mildred, Kaboggoza, Olivia, Kadhuba, Rose Jacqueline, Kaewbundit, Ampika, Kaewmamueng, Kanyanee, Kafufu, Bosco, Kakayi, Brenda, Kamboua, Phakamas, Kanjanavanit, Suparat, Kasangaki, Gladys, Kasipong, Naruporn, Kasozi, Miriam, Kataike, Hajira, Katemba, Chrispus, Kaudha, Elizabeth, Kekane, Nkata, Kekitiinwa, Adeodata R, Keminyeto, Edridah, Khamduang, Woottichai, Khamjakkaew, Warunee, Khamkon, Jiraporn, Khannak, Sasipass, Khatngam, Orapin, Khayanchoomnoom, Tassawan, Khumalo, Busi, Khunene, Mirriam, Khusuwan, Suwimon, Kibalama, Phionah, Kibenge, Robinah, Kirabira, Anthony, Kityo, Cissy M, Kiyimba, Lameck, Klein, Nigel, Klinprung, Soraya, Kobbe, Robin, Kobusingye, Olivia, Kobusungye, Josephine, Kongponoi, Areerat, Königs, Christoph, Koole, Olivier, Kouakam, Christelle, Krueduangkam, Nitinart, Kruenual, Namthip, Kunjaroenrut, Nuananong, Kyambadde, Raymonds, Kyobutungi, Priscilla, Kyomuhendo, Flavia, Kyomukama, Erinah, Lakha, Reshma, Langa, Cleopatra, Laomanit, Laddawan, Lebotsa, Emily, Leenasirimakul, Prattana, Lekku, Lawrence, Lensen, Sarah, Leroy, Valériane, Li, Jin, Liberty, Afaaf, Limplertjareanwanich, Juthamas, Little, Emma, Lugemwa, Abbas, Lutalo, Ezra, Jimenez, Jose Luis, Lyall, Hermione, MacDonald, Candice, Machache, Gladness, Madlala, Penelope, Madonsela, Tryphina, Maduna, Nomfundo, Maena, Joel, Mahanontharit, Apicha, Makanga, Collin, Makola, Candice, Makumbi, Shafic, Malgraaf, Lucille, Mamiane, Angelous, Mantkowski, Felicia, Mapfumo, Wendy, Marques, Laura, Mugagga, Agnes Mary, Maseko, Lindiwe, Masienyane, Tshepiso, Mathiba, Ruth, Matimba, Farai, Mawlana, Sajeeda, Mayanja, Emmanuel, Mayat, Fatima, Mbabazi, Ritah, Mbadaliga, Nokuthula, Mbasani, Faith, McClaughlin, Kathleen, McIlleron, Helen, Meethaisong, Watchara, Mendez Garcia, Patricia, Miwanda, Annet, Miranda, Carlota, Mkhize, Siphiwe, Mmolawa, Kgosimang, Mngqibisa, Rosie, Mohamed, Fatima, Moloantoa, Tumelo, Monametsi, Maletsatsi, Montero, Samuel, Moore, Cecilia L, Mosia, Rejoice, Moyo, Columbus, Mthethwa, Mumsy, Mudzingwa, Shepherd, Mudzviti, Tawona, Mujuru, Hilda, Mujyambere, Emmanuel, Mukanganiki, Trust, Mukisa Williams, Cynthia, Mulder, Mark, Mulima, Disan, Mulindwa, Alice, Mumbiro, Vivian, Mupambireyi, Zivai, Murciano Cabeza, Alba, Murungi, Herbert, Murungu, Dorothy, Musarurwa, Sandra, Musiime, Victor, Musiime, Alex V, Musisi, Maria, Musoke, Philippa, Musoke Nakirya, Barbara, Musoro, Godfrey, Musumba, Sharif, Mustafa, Sobia, Mutsai, Shirley, Mwesigwa Rubondo, Phyllis, Naabalamba, Mariam, Nagawa, Immaculate, Naidoo, Allemah, Nakabuye, Shamim, Nakabuye, Sarah, Nakalanzi, Sarah, Nalubwama, Justine, Nalugo, Annet, Nalusiba, Stella, Namajja, Clementine, Namanda, Sylvia, Namayanja, Paula, Nambi, Esther, Namuddu, Rachael Kikabi, Namukwaya, Stella, Namuli, Florence, Namusanje, Josephine, Namwanje, Rosemary, Nanan-kanjee, Anusha, Nanduudu, Annet, Nankunda, Charity, Baddokwaya, Joanita Nankya, Nannungi, Maria, Nansamba, Winnie, Nanthapisal, Kesdao, Nanyonjo, Juliet, Na-Rajsima, Sathaporn, Nasaazi, Claire, Nascimento, Helena, Nastouli, Eleni, Songtaweesin, Wipaporn Natalie, Nathoo, Kusum, Natuhurira, Ian, Nazzinda, Rashidah, Ncgaba, Thabisa, Ndigendawani, Milly, Ndlovu, Makhosonke, Nentsa, Georgina, Ngampiyaskul, Chaiwat, Ngcobo, Ntombenhle, Ngo Giang Huong, Nicole, Ngwaru, Pia, Nhema, Ruth, Ninsiima, Emily, Ninsiima, Gloria, Nkalo Phiri, Misheck, Noguera Julian, Antoni, Nolan, Monica, Noppakaorattanamanee, Thornthun, Nsibuka Kisekka, Muzamil, Nsirim, Eniola, Nundlal, Rashina, Nunes, Rosita, Nyantsa, Lungile, Nyati, Mandisa, O'Riordan, Sean, Ocitti Labeja, Paul, Odoch, Denis, Oguntimehin, Rachel, Ojok, Martin, Onen, Geoffrey, Orange, Wilma, Ounchanum, Pradthana, Ouma, Benson, Padrao, Andreia, Pako, Deborah, Parker, Anna, Pasko-Szcech, Malgorzata, Patel, Reena, Peongjakta, Rukchanok, Petpranee, Turian, Phillips, Tasmin, Philps, Jackie, Picault, Laura, Pieterse, Sonja, Pinheiro, Helena, Pongprapass, Supawadee, Pozniak, Anton, Prendergast, Andrew, Prieto Tato, Luis, Puangmalai, Patcharee, Puthanakit, Thanyawee, Rakgokong, Modiehi, Ramos, Helena, Ramsagar, Nastassja, Rau, Cornelius, Riault, Yoann, Rojo Conejo, Pablo, Clark, Basiimwa Roy, Rubanga, Eddie, Rubinga, Baker, Ruklao, Chutima, Runarassamee, Pattira, Rutebarika, Diana Antonia, Saenjum, Chalermpong, Saewtrakool, Chayakorn, Saidi, Yacine, Sainz Costa, Talia, Saisaengjan, Chutima, Sakwa, Rebecca, Sarfati, Tatiana, Sbisi, Noshalaza, Scheppers, Dihedile, Schultze-Strasser, Stephan, Schulze-Sturm, Ulf, Scott, Karen, Seeley, Janet, Serunjogi, Robert, Sewnarain, Leora, Shakeshaft, Clare, Sidhoo, Subashinie, Shibemba, Mercy, Shingadia, Delane, Singh, Sheleika, Sirirungsi, Wasna, Sithebe, Sibongile, Smit, Theresa, Smith, Kurt, Smuts, Marlize, Spyer, Moira, Sripaoraya, Worathip, Srirompotong, Ussanee, Srisuk, Warunee, Ssenyonga, Mark, Sudsaard, Patamawadee, Sukrakanchana, Praornsuda, Tearsansern, Pathanee, Teixeira, Carla, Than-in-at, Kanchana, Thapwai, Thitiwat, Thaweesombat, Yupawan, Thewsoongnoen, Jutarat, Thiébaut, Rodolphe, Thomason, Margaret, Thrasyvoulou, Laura, Thungkham, Khanungnit, Tikabibamu, Judith, Tinago, Gloria, Trairat, Ketmookda, Tudor-Williams, Gareth, Tukamushaba, Mercy, Tukwasibwe, Deogratiuos, Tumusiime, Julius, Tuna, Joana, Turkova, Anna, Turner, Rebecca, Udomvised, Arttasid, Vadee, Aasia, Van Huyssteen, Hesti, Van Looy, Nadine, Variava, Ebrahim, Vaughan-Gordon, Yvonne, Vecchia, Giulio, Violari, Avy, Vowden, Richard, Waalewijn, Hylke, Wampamba, Rebecca, Welch, Steve, Weller, Ian, Weza, Sibusisiwe, White, Ellen, White, Ian, Widuch, Kaja, Wilkes, Helen, Wimonklang, Sookpanee, Wynne, Ben, Yingyong, Pacharaporn, Nakawungu, Zaam Zinda, and Zuidewind, Peter

Abstract

Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy.

Published
2023
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24. Design and Synthesis of Inhibitors of the E3 Ligase SMAD Specific E3 Ubiquitin Protein Ligase 1 as a Treatment for Lung Remodeling in Pulmonary Arterial Hypertension.

Author

Shaw, Duncan E., Smith, Nichola, Beerli, Rene, Cotesta, Simona, D'Alessandro, Pier-Luca, Edwards, Anne-Marie, Lattmann, Rene, Lizos, Dimitrios, Pulz, Robert, Rooney, Lisa, Sohal, Bindi, Rynn, Caroline, Taylor, Jessica, Troxler, Thomas, Williams, Gareth, Guth, Sabine, and Rowlands, David

Published
2023
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25. Wearable technology and the cardiovascular system: the future of patient assessment

Author

Williams, Gareth J, Al-Baraikan, Abdulaziz, Rademakers, Frank E, Ciravegna, Fabio, van de Vosse, Frans N, Lawrie, Allan, Rothman, Alexander, Ashley, Euan A, Wilkins, Martin R, Lawford, Patricia V, Omholt, Stig W, Wisløff, Ulrik, Hose, D Rodney, Chico, Timothy J A, Gunn, Julian P, and Morris, Paul D

Abstract

The past decade has seen a dramatic rise in consumer technologies able to monitor a variety of cardiovascular parameters. Such devices initially recorded markers of exercise, but now include physiological and health-care focused measurements. The public are keen to adopt these devices in the belief that they are useful to identify and monitor cardiovascular disease. Clinicians are therefore often presented with health app data accompanied by a diverse range of concerns and queries. Herein, we assess whether these devices are accurate, their outputs validated, and whether they are suitable for professionals to make management decisions. We review underpinning methods and technologies and explore the evidence supporting the use of these devices as diagnostic and monitoring tools in hypertension, arrhythmia, heart failure, coronary artery disease, pulmonary hypertension, and valvular heart disease. Used correctly, they might improve health care and support research.

Published
2023
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26. New stable high-drug-loading amorphous solid dispersions from electrospinning

Author

Williams, Gareth R. and Majumder, Mridul

Abstract

Electrospinning is a technique that can be used to fabricate amorphous solid dispersions and thus overcome the major challenge of poor drug solubility. However, the majority of studies in the literature work at relatively low drug loadings (<30% w/w). Recent work by Becelaere et al. to overcome this challenge and increase loading to >50% is discussed in this preview.

Published
2024
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27. A piezoelectric catalytic cascade nanoreactor which reshapes the tumor microenvironment and promotes effective multi-dimensional therapy.

Author

Zheng, Yilu, Du, Yichao, Williams, Gareth R., Zhu, Ying, Wang, Tong, Zhang, Yanyan, Xu, Jianxiang, Wu, Junzi, Li, Fan, and Zhu, Li-Min

Abstract

The nature of the tumor microenvironment (TME) is often a hindrance to effective cancer therapy and results in treatment failure. Here, a nanoparticle cascade catalyst has been developed. This platform, Ber/CoFe 2 O 4 @PSiO 2 -KCN, is based on CoFe 2 O 4 nanoparticles which are then coated with silica, functionalized with potassium doped carbon nitride (KCN) and loaded with the drug berberine (Ber). Ber/CoFe 2 O 4 @PSiO 2 -KCN in combination with ultrasound is found to have the ability to generate gluconic acid and H 2 O 2 from glucose and convert H 2 O 2 to ·OH to provide effective chemodynamic therapy. Ber promotes the accumulation of lactic acid in tumor cells, acidifying the TME and facilitating the catalytic reactions of KCN and CoFe 2 O 4. The oxidative stress generated by the presence of large amounts of ·OH in the tumor triggers cell apoptosis, the production of damage-associated molecular pathways, and thus induces immunogenic cell death. The potent anti-tumor effects and imaging function of Ber/CoFe 2 O 4 @PSiO 2 -KCN could be applied as a future anti-cancer therapy. [Display omitted] • Multifunctional nanoparticles (NPs) are developed to enhance cancer therapy. • The NPs can catalyze the conversion of glucose to gluconic acid for starvation therapy. • The NPs further catalyze the production of reactive oxygen species. • In vitro and in vivo results evidence synergistic death of cancer cells. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Amplified EQCM-D detection of extracellular vesicles using 2D gold nanostructured arrays fabricated by block copolymer self-assemblyElectronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d2nh00424k

Author

Suthar, Jugal, Alvarez-Fernandez, Alberto, Osarfo-Mensah, Esther, Angioletti-Uberti, Stefano, Williams, Gareth R., and Guldin, Stefan

Abstract

Extracellular vesicles (EVs) are routinely released from nearly all cell types as transport vehicles and for cell communication. Crucially, they contain biomolecular content for the identification of health and disease states that can be detected from readily accessible physiological fluids, including urine, plasma, or saliva. Despite their clinical utility within noninvasive diagnostic platforms such as liquid biopsies, the currently available portfolio of analytical approaches are challenged by EV heterogeneity in size and composition, as well as the complexity of native biofluids. Quartz crystal microbalance with dissipation monitoring (QCM-D) has recently emerged as a powerful alternative for the phenotypic detection of EVs, offering multiple modes of analyte discrimination by frequency and dissipation. While providing rich data for sensor development, further progress is required to reduce detection limits and fully exploit the technique's potential within biosensing. Herein, we investigate the impact of nanostructuring the sensor electrode surface for enhancing its detection capabilities. We employ self-assembly of the block copolymer polystyrene-block-poly(4-vinylpyridine) to create well defined 2D gold islands viaselective impregnation of the pyridine domain with gold precursors and subsequent removal of the template. When matched to the EV length scale, we find a 4-fold improvement in sensitivity despite a 4-fold reduction in area for analyte and ligand anchoring in comparison to a flat sensor surface. Creation of tailored and confined sensing regions interspersed by non-binding silica provides optimal spatial orientation for EV capture with reduced steric effects and negative cooperativity of grafted antibodies, offering a promising route for facilitated binding and enhanced performance of sensor platforms.

Published
2023
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31. Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Author

Turkova, Anna, Waalewijn, Hylke, Chan, Man K, Bollen, Pauline D J, Bwakura-Dangarembizi, Mutsa F, Kekitiinwa, Adeodata R, Cotton, Mark F, Lugemwa, Abbas, Variava, Ebrahim, Ahimbisibwe, Grace Miriam, Srirompotong, Ussanee, Mumbiro, Vivian, Amuge, Pauline, Zuidewind, Peter, Ali, Shabinah, Kityo, Cissy M, Archary, Moherndran, Ferrand, Rashida A, Violari, Avy, Gibb, Diana M, Burger, David M, Ford, Deborah, Colbers, Angela, Mehar (nee Abdulla), Amina Farhana, Abraham, Pattamukkil, Abrams, Elaine, Acero, Judith, Agaba, Gerald Muzorah, Ahimbisibwe, Grace, Ainebyoona, Barbara, Akobye, Winnie, Akhalwaya, Yasmeen, Akoojee, Nazim, Ali, Shabinah S., Amuge, Pauline, Andrea, Catherine, Muñoz Fernandez, Maria Angeles, Ankunda, Rogers, Rutebarika, Diana Antonia, Anugulruengkitt, Suvaporn, Apollo, Tsitsi, Archary, Moherndran, Arendze, Ronelle, Ategeka, Juliet, Atim, Eunice, Atwine, Lorna, Babiker, Abdel, Babirye, Sarah, Babu, Enock, Bagirigomwa, Edward, Baita, Angella, Balamusani, David, Baliram, Patsy, Baliruno, David, Ball, Colin, Balwa, Henry, Bamford, Alasdair, Bandi, Srini, Barker, Dominique, Barlow-Mosha, Linda, Bbuye, Dickson, Begum, Shazia, Behuhuma, Osee, Bernays, Sarah, Besigye, Rogers, Bester, Maria, Bhiri, Joyline, Bilardi, Davide, Bird, Kristien, Bollen, Pauline, Borg, Chiara, Borges Da Silva, Anne-Marie, Brown, Jackie, Bruno, Elena, Bunupuradah, Torsak, Burger, David, Buthelezi, Nomzamo, Bwakura-Dangarembizi, Mutsa, Byaruhanga, Africanus, Calvert, Joanna, Casey, Petronelle, Cassim, Haseena, Cebekhulu, Sphiwee, Chailert, Sanuphong, Chalermpantmetagul, Suwalai, Chamjamrat, Wanna, Chan, Man, Chandiwana, Precious, Chankun, Thannapat, Chanthaburanun, Sararut, Chanto, Nuttawut, Chidziva, Ennie, Chikowore, Minenhle, Chimanzi, Joy, Chinwong, Dujrudee, Chitongo, Stuart, Chitsamatanga, Moses, Choga, Joshua, Chutima, Duangrat, Clayden, Polly, Coelho, Alexandra, Colbers, Angela, Compagnucci, Alexandra, Constança Mendes, Ana, Conway, Magda, Cotton, Mark F., Crawley, Jane, Cressey, Tim R., Crisp, Jacky, Matos, Ana Cristina, Dadan, Sumaya, Daglish, Jacqui, Danaviah, Siva, Daniel, Tseleng, De Rossi, Anita, Denjanta, Sukanda, Dobbels, Els, Dowie, Maria, Dube, Prosper, Dube, Benedictor, Dudakia, Nimisha, Elwana, Alice, Epalza, Cristina, Eram, David, Erasmus, Juan, Erim, Peter, Escosa Garcia, Luis, Essack, Zaakirah, Estepa, Carolina, Etima, Monica, Fernandes, Alexandre, Fernandez, Maite, Fitzgerald, Felicity, Flynn, Jacquie, Ford, Deborah, Fortuny Guasch, Claudia, Foster, Caroline, Fourie, George, Fourie, Yolandie, Foxall, Sophie, Frank, Derusha, Gandhi, Kate, Garcia, India, Gartner, Kathleen, Gasa, Joshua, Gasa, Gugu, Giaquinto, Carlo, Gibb, Diana M., Gomez Rico, Coral, Gomez-Pena, Daniel, Gondo, Secrecy, Goodman, Anna, Gorreti Nakalema, Maria, Gozhora, Winnie, Greetanukroh, Pisut, Gregorio Maranon, Biobanco, Grossele, Tiziana, Gwande, Shamiso, Gwaze, Tapiwa, Gwenzi, Tsitsi, Hakim, James, Hakiza, Emmanuel, Kaka, Abdul Hamid, Harley, Ashley, Isaacs, Mornay, Isabirye, Richard, Ishemunyoro, Wilber, Jacobs, Tom, Jafta, Lungile, Jamil, Nasir, Janse van Rensburg, Anita Janse, Jeaven, Vinesh, Mellado Peña, Maria José, Jourdain, Gonzague, Juliet, Katabalwa, Jumpimai, Thidarat, Junkaew, Raungwit, Jupimai, Thidarat, Kaahwa, Winfred, Kabasonga, Mildred, Kaboggoza, Olivia, Kadhuba, Rose Jacqueline, Kaewbundit, Ampika, Kaewmamueng, Kanyanee, Kafufu, Bosco, Kakayi, Brenda, Kamboua, Phakamas, Kanjanavanit, Suparat, Kasangaki, Gladys, Kasipong, Naruporn, Kasozi, Miriam, Kataike, Hajira, Katemba, Chrispus, Kaudha, Elizabeth, Kekane, Nkata, Kekitiinwa, Adeodata R., Keminyeto, Edridah, Khamduang, Woottichai, Khamjakkaew, Warunee, Khamkon, Jiraporn, Khannak, Sasipass, Khatngam, Orapin, Khayanchoomnoom, Tassawan, Khumalo, Busi, Khunene, Mirriam, Khusuwan, Suwimon, Kibalama, Phionah, Kibenge, Robinah, Kirabira, Anthony, Kityo, Cissy M., Kiyimba, Lameck, Klein, Nigel, Klinprung, Soraya, Kobbe, Robin, Kobusingye, Olivia, Kobusungye, Josephine, Kongponoi, Areerat, Königs, Christoph, Koole, Olivier, Kouakam, Christelle, Krueduangkam, Nitinart, Kruenual, Namthip, Kunjaroenrut, Nuananong, Kyambadde, Raymonds, Kyobutungi, Priscilla, Kyomuhendo, Flavia, Kyomukama, Erinah, Lakha, Reshma, Langa, Cleopatra, Laomanit, Laddawan, Lebotsa, Emily, Leenasirimakul, Prattana, Lekku, Lawrence, Lensen, Sarah, Leroy, Valériane, Li, Jin, Liberty, Afaaf, Limplertjareanwanich, Juthamas, Little, Emma, Lugemwa, Abbas, Lutalo, Ezra, Jimenez, Jose Luis, Lyall, Hermione, MacDonald, Candice, Machache, Gladness, Madlala, Penelope, Madonsela, Tryphina, Maduna, Nomfundo, Maena, Joel, Mahanontharit, Apicha, Makanga, Collin, Makola, Candice, Makumbi, Shafic, Malgraaf, Lucille, Mamiane, Angelous, Mantkowski, Felicia, Mapfumo, Wendy, Marques, Laura, Mugagga, Agnes Mary, Maseko, Lindiwe, Masienyane, Tshepiso, Mathiba, Ruth, Matimba, Farai, Mawlana, Sajeeda, Mayanja, Emmanuel, Mayat, Fatima, Mbabazi, Ritah, Mbadaliga, Nokuthula, Mbasani, Faith, McClaughlin, Kathleen, McIlleron, Helen, Meethaisong, Watchara, Mendez Garcia, Patricia, Miwanda, Annet, Miranda, Carlota, Mkhize, Siphiwe, Mmolawa, Kgosimang, Mngqibisa, Rosie, Mohamed, Fatima, Moloantoa, Tumelo, Monametsi, Maletsatsi, Montero, Samuel, Moore, Cecilia L., Mosia, Rejoice, Moyo, Columbus, Mthethwa, Mumsy, Mudzingwa, Shepherd, Mudzviti, Tawona, Mujuru, Hilda, Mujyambere, Emmanuel, Mukanganiki, Trust, Mukisa Williams, Cynthia, Mulder, Mark, Mulima, Disan, Mulindwa, Alice, Mumbiro, Vivian, Mupambireyi, Zivai, Murciano Cabeza, Alba, Murungi, Herbert, Murungu, Dorothy, Musarurwa, Sandra, Musiime, Victor, Musiime, Alex V., Musisi, Maria, Musoke, Philippa, Musoke Nakirya, Barbara, Musoro, Godfrey, Musumba, Sharif, Mustafa, Sobia, Mutsai, Shirley, Mwesigwa Rubondo, Phyllis, Naabalamba, Mariam, Nagawa, Immaculate, Naidoo, Allemah, Nakabuye, Shamim, Nakabuye, Sarah, Nakalanzi, Sarah, Nalubwama, Justine, Nalugo, Annet, Nalusiba, Stella, Namajja, Clementine, Namanda, Sylvia, Namayanja, Paula, Nambi, Esther, Namuddu, Rachael Kikabi, Namukwaya, Stella, Namuli, Florence, Namusanje, Josephine, Namwanje, Rosemary, Nanan-kanjee, Anusha, Nanduudu, Annet, Nankunda, Charity, Baddokwaya, Joanita Nankya, Nannungi, Maria, Nansamba, Winnie, Nanthapisal, Kesdao, Nanyonjo, Juliet, Na-Rajsima, Sathaporn, Nasaazi, Claire, Nascimento, Helena, Nastouli, Eleni, Songtaweesin, Wipaporn Natalie, Nathoo, Kusum, Natuhurira, Ian, Nazzinda, Rashidah, Ncgaba, Thabisa, Ndigendawani, Milly, Ndlovu, Makhosonke, Nentsa, Georgina, Ngampiyaskul, Chaiwat, Ngcobo, Ntombenhle, Ngo Giang Huong, Nicole, Ngwaru, Pia, Nhema, Ruth, Ninsiima, Emily, Ninsiima, Gloria, Nkalo Phiri, Misheck, Noguera Julian, Antoni, Nolan, Monica, Noppakaorattanamanee, Thornthun, Nsibuka Kisekka, Muzamil, Nsirim, Eniola, Nundlal, Rashina, Nunes, Rosita, Nyantsa, Lungile, Nyati, Mandisa, O'Riordan, Sean, Ocitti Labeja, Paul, Odoch, Denis, Oguntimehin, Rachel, Ojok, Martin, Onen, Geoffrey, Orange, Wilma, Ounchanum, Pradthana, Ouma, Benson, Padrao, Andreia, Pako, Deborah, Parker, Anna, Pasko-Szcech, Malgorzata, Patel, Reena, Peongjakta, Rukchanok, Petpranee, Turian, Phillips, Tasmin, Philps, Jackie, Picault, Laura, Pieterse, Sonja, Pinheiro, Helena, Pongprapass, Supawadee, Pozniak, Anton, Prendergast, Andrew, Prieto Tato, Luis, Puangmalai, Patcharee, Puthanakit, Thanyawee, Rakgokong, Modiehi, Ramos, Helena, Ramsagar, Nastassja, Rau, Cornelius, Riault, Yoann, Rojo Conejo, Pablo, Clark, Basiimwa Roy, Rubanga, Eddie, Rubinga, Baker, Ruklao, Chutima, Runarassamee, Pattira, Rutebarika, Diana Antonia, Saenjum, Chalermpong, Saewtrakool, Chayakorn, Saidi, Yacine, Sainz Costa, Talia, Saisaengjan, Chutima, Sakwa, Rebecca, Sarfati, Tatiana, Sbisi, Noshalaza, Scheppers, Dihedile, Schultze-Strasser, Stephan, Schulze-Sturm, Ulf, Scott, Karen, Seeley, Janet, Serunjogi, Robert, Sewnarain, Leora, Shakeshaft, Clare, Sidhoo, Subashinie, Shibemba, Mercy, Shingadia, Delane, Singh, Sheleika, Sirirungsi, Wasna, Sithebe, Sibongile, Smit, Theresa, Smith, Kurt, Smuts, Marlize, Spyer, Moira, Sripaoraya, Worathip, Srirompotong, Ussanee, Srisuk, Warunee, Ssenyonga, Mark, Sudsaard, Patamawadee, Sukrakanchana, Praornsuda, Tearsansern, Pathanee, Teixeira, Carla, Than-in-at, Kanchana, Thapwai, Thitiwat, Thaweesombat, Yupawan, Thewsoongnoen, Jutarat, Thiébaut, Rodolphe, Thomason, Margaret, Thrasyvoulou, Laura, Thungkham, Khanungnit, Tikabibamu, Judith, Tinago, Gloria, Trairat, Ketmookda, Tudor-Williams, Gareth, Tukamushaba, Mercy, Tukwasibwe, Deogratiuos, Tumusiime, Julius, Tuna, Joana, Turkova, Anna, Turner, Rebecca, Udomvised, Arttasid, Vadee, Aasia, Van Huyssteen, Hesti, Van Looy, Nadine, Variava, Ebrahim, Vaughan-Gordon, Yvonne, Vecchia, Giulio, Violari, Avy, Vowden, Richard, Waalewijn, Hylke, Wampamba, Rebecca, Welch, Steve, Weller, Ian, Weza, Sibusisiwe, White, Ellen, White, Ian, Widuch, Kaja, Wilkes, Helen, Wimonklang, Sookpanee, Wynne, Ben, Yingyong, Pacharaporn, Nakawungu, Zaam Zinda, and Zuidewind, Peter

Abstract

Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB.

Published
2022
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32. Once-daily dolutegravir-based antiretroviral therapy in infants and children living with HIV from age 4 weeks: results from the below 14 kg cohort in the randomised ODYSSEY trial

Author

Amuge, Pauline, Lugemwa, Abbas, Wynne, Ben, Mujuru, Hilda A, Violari, Avy, Kityo, Cissy M, Archary, Moherndran, Variava, Ebrahim, White, Ellen, Turner, Rebecca M, Shakeshaft, Clare, Ali, Shabinah, Nathoo, Kusum J, Atwine, Lorna, Liberty, Afaaf, Bbuye, Dickson, Kaudha, Elizabeth, Mngqibisa, Rosie, Mosala, Modehei, Mumbiro, Vivian, Nanduudu, Annet, Ankunda, Rogers, Maseko, Lindiwe, Kekitiinwa, Adeodata R, Giaquinto, Carlo, Rojo, Pablo, Gibb, Diana M, Turkova, Anna, Ford, Deborah, Mehar (nee Abdulla), Amina Farhana, Abraham, Pattamukkil, Abrams, Elaine, Acero, Judith, Agaba, Gerald Muzorah, Ahimbisibwe, Grace, Ainebyoona, Barbara, Akobye, Winnie, Akhalwaya, Yasmeen, Akoojee, Nazim, Ali, Shabinah S., Amuge, Pauline, Andrea, Catherine, Muñoz Fernandez, Maria Angeles, Ankunda, Rogers, Rutebarika, Diana Antonia, Anugulruengkitt, Suvaporn, Apollo, Tsitsi, Archary, Moherndran, Arendze, Ronelle, Ategeka, Juliet, Atim, Eunice, Atwine, Lorna, Babiker, Abdel, Babirye, Sarah, Babu, Enock, Bagirigomwa, Edward, Baita, Angella, Balamusani, David, Baliram, Patsy, Baliruno, David, Ball, Colin, Balwa, Henry, Bamford, Alasdair, Bandi, Srini, Barker, Dominique, Barlow-Mosha, Linda, Bbuye, Dickson, Begum, Shazia, Behuhuma, Osee, Bernays, Sarah, Besigye, Rogers, Bester, Maria, Bhiri, Joyline, Bilardi, Davide, Bird, Kristien, Bollen, Pauline, Borg, Chiara, Borges Da Silva, Anne-Marie, Brown, Jackie, Bruno, Elena, Bunupuradah, Torsak, Burger, David, Buthelezi, Nomzamo, Bwakura-Dangarembizi, Mutsa, Byaruhanga, Africanus, Calvert, Joanna, Casey, Petronelle, Cassim, Haseena, Cebekhulu, Sphiwee, Chailert, Sanuphong, Chalermpantmetagul, Suwalai, Chamjamrat, Wanna, Chan, Man, Chandiwana, Precious, Chankun, Thannapat, Chanthaburanun, Sararut, Chanto, Nuttawut, Chidziva, Ennie, Chikowore, Minenhle, Chimanzi, Joy, Chinwong, Dujrudee, Chitongo, Stuart, Chitsamatanga, Moses, Choga, Joshua, Chutima, Duangrat, Clayden, Polly, Coelho, Alexandra, Colbers, Angela, Compagnucci, Alexandra, Constança Mendes, Ana, Conway, Magda, Cotton, Mark F., Crawley, Jane, Cressey, Tim R., Crisp, Jacky, Matos, Ana Cristina, Dadan, Sumaya, Daglish, Jacqui, Danaviah, Siva, Daniel, Tseleng, De Rossi, Anita, Denjanta, Sukanda, Dobbels, Els, Dowie, Maria, Dube, Prosper, Dube, Benedictor, Dudakia, Nimisha, Elwana, Alice, Epalza, Cristina, Eram, David, Erasmus, Juan, Erim, Peter, Escosa Garcia, Luis, Essack, Zaakirah, Estepa, Carolina, Etima, Monica, Fernandes, Alexandre, Fernandez, Maite, Fitzgerald, Felicity, Flynn, Jacquie, Ford, Deborah, Fortuny Guasch, Claudia, Foster, Caroline, Fourie, George, Fourie, Yolandie, Foxall, Sophie, Frank, Derusha, Gandhi, Kate, Garcia, India, Gartner, Kathleen, Gasa, Joshua, Gasa, Gugu, Giaquinto, Carlo, Gibb, Diana M., Gomez Rico, Coral, Gomez-Pena, Daniel, Gondo, Secrecy, Goodman, Anna, Gorreti Nakalema, Maria, Gozhora, Winnie, Greetanukroh, Pisut, Gregorio Maranon, Biobanco, Grossele, Tiziana, Gwande, Shamiso, Gwaze, Tapiwa, Gwenzi, Tsitsi, Hakim, James, Hakiza, Emmanuel, Kaka, Abdul Hamid, Harley, Ashley, Isaacs, Mornay, Isabirye, Richard, Ishemunyoro, Wilber, Jacobs, Tom, Jafta, Lungile, Jamil, Nasir, Janse van Rensburg, Anita Janse, Jeaven, Vinesh, Mellado Peña, Maria José, Jourdain, Gonzague, Juliet, Katabalwa, Jumpimai, Thidarat, Junkaew, Raungwit, Jupimai, Thidarat, Kaahwa, Winfred, Kabasonga, Mildred, Kaboggoza, Olivia, Kadhuba, Rose Jacqueline, Kaewbundit, Ampika, Kaewmamueng, Kanyanee, Kafufu, Bosco, Kakayi, Brenda, Kamboua, Phakamas, Kanjanavanit, Suparat, Kasangaki, Gladys, Kasipong, Naruporn, Kasozi, Miriam, Kataike, Hajira, Katemba, Chrispus, Kaudha, Elizabeth, Kekane, Nkata, Kekitiinwa, Adeodata R., Keminyeto, Edridah, Khamduang, Woottichai, Khamjakkaew, Warunee, Khamkon, Jiraporn, Khannak, Sasipass, Khatngam, Orapin, Khayanchoomnoom, Tassawan, Khumalo, Busi, Khunene, Mirriam, Khusuwan, Suwimon, Kibalama, Phionah, Kibenge, Robinah, Kirabira, Anthony, Kityo, Cissy M., Kiyimba, Lameck, Klein, Nigel, Klinprung, Soraya, Kobbe, Robin, Kobusingye, Olivia, Kobusungye, Josephine, Kongponoi, Areerat, Königs, Christoph, Koole, Olivier, Kouakam, Christelle, Krueduangkam, Nitinart, Kruenual, Namthip, Kunjaroenrut, Nuananong, Kyambadde, Raymonds, Kyobutungi, Priscilla, Kyomuhendo, Flavia, Kyomukama, Erinah, Lakha, Reshma, Langa, Cleopatra, Laomanit, Laddawan, Lebotsa, Emily, Leenasirimakul, Prattana, Lekku, Lawrence, Lensen, Sarah, Leroy, Valériane, Li, Jin, Liberty, Afaaf, Limplertjareanwanich, Juthamas, Little, Emma, Lugemwa, Abbas, Lutalo, Ezra, Jimenez, Jose Luis, Lyall, Hermione, MacDonald, Candice, Machache, Gladness, Madlala, Penelope, Madonsela, Tryphina, Maduna, Nomfundo, Maena, Joel, Mahanontharit, Apicha, Makanga, Collin, Makola, Candice, Makumbi, Shafic, Malgraaf, Lucille, Mamiane, Angelous, Mantkowski, Felicia, Mapfumo, Wendy, Marques, Laura, Mugagga, Agnes Mary, Maseko, Lindiwe, Masienyane, Tshepiso, Mathiba, Ruth, Matimba, Farai, Mawlana, Sajeeda, Mayanja, Emmanuel, Mayat, Fatima, Mbabazi, Ritah, Mbadaliga, Nokuthula, Mbasani, Faith, McClaughlin, Kathleen, McIlleron, Helen, Meethaisong, Watchara, Mendez Garcia, Patricia, Miwanda, Annet, Miranda, Carlota, Mkhize, Siphiwe, Mmolawa, Kgosimang, Mngqibisa, Rosie, Mohamed, Fatima, Moloantoa, Tumelo, Monametsi, Maletsatsi, Montero, Samuel, Moore, Cecilia L., Mosia, Rejoice, Moyo, Columbus, Mthethwa, Mumsy, Mudzingwa, Shepherd, Mudzviti, Tawona, Mujuru, Hilda, Mujyambere, Emmanuel, Mukanganiki, Trust, Mukisa Williams, Cynthia, Mulder, Mark, Mulima, Disan, Mulindwa, Alice, Mumbiro, Vivian, Mupambireyi, Zivai, Murciano Cabeza, Alba, Murungi, Herbert, Murungu, Dorothy, Musarurwa, Sandra, Musiime, Victor, Musiime, Alex V., Musisi, Maria, Musoke, Philippa, Musoke Nakirya, Barbara, Musoro, Godfrey, Musumba, Sharif, Mustafa, Sobia, Mutsai, Shirley, Mwesigwa Rubondo, Phyllis, Naabalamba, Mariam, Nagawa, Immaculate, Naidoo, Allemah, Nakabuye, Shamim, Nakabuye, Sarah, Nakalanzi, Sarah, Nalubwama, Justine, Nalugo, Annet, Nalusiba, Stella, Namajja, Clementine, Namanda, Sylvia, Namayanja, Paula, Nambi, Esther, Namuddu, Rachael Kikabi, Namukwaya, Stella, Namuli, Florence, Namusanje, Josephine, Namwanje, Rosemary, Nanan-kanjee, Anusha, Nanduudu, Annet, Nankunda, Charity, Baddokwaya, Joanita Nankya, Nannungi, Maria, Nansamba, Winnie, Nanthapisal, Kesdao, Nanyonjo, Juliet, Na-Rajsima, Sathaporn, Nasaazi, Claire, Nascimento, Helena, Nastouli, Eleni, Songtaweesin, Wipaporn Natalie, Nathoo, Kusum, Natuhurira, Ian, Nazzinda, Rashidah, Ncgaba, Thabisa, Ndigendawani, Milly, Ndlovu, Makhosonke, Nentsa, Georgina, Ngampiyaskul, Chaiwat, Ngcobo, Ntombenhle, Ngo Giang Huong, Nicole, Ngwaru, Pia, Nhema, Ruth, Ninsiima, Emily, Ninsiima, Gloria, Nkalo Phiri, Misheck, Noguera Julian, Antoni, Nolan, Monica, Noppakaorattanamanee, Thornthun, Nsibuka Kisekka, Muzamil, Nsirim, Eniola, Nundlal, Rashina, Nunes, Rosita, Nyantsa, Lungile, Nyati, Mandisa, O'Riordan, Sean, Ocitti Labeja, Paul, Odoch, Denis, Oguntimehin, Rachel, Ojok, Martin, Onen, Geoffrey, Orange, Wilma, Ounchanum, Pradthana, Ouma, Benson, Padrao, Andreia, Pako, Deborah, Parker, Anna, Pasko-Szcech, Malgorzata, Patel, Reena, Peongjakta, Rukchanok, Petpranee, Turian, Phillips, Tasmin, Philps, Jackie, Picault, Laura, Pieterse, Sonja, Pinheiro, Helena, Pongprapass, Supawadee, Pozniak, Anton, Prendergast, Andrew, Prieto Tato, Luis, Puangmalai, Patcharee, Puthanakit, Thanyawee, Rakgokong, Modiehi, Ramos, Helena, Ramsagar, Nastassja, Rau, Cornelius, Riault, Yoann, Rojo Conejo, Pablo, Clark, Basiimwa Roy, Rubanga, Eddie, Rubinga, Baker, Ruklao, Chutima, Runarassamee, Pattira, Rutebarika, Diana Antonia, Saenjum, Chalermpong, Saewtrakool, Chayakorn, Saidi, Yacine, Sainz Costa, Talia, Saisaengjan, Chutima, Sakwa, Rebecca, Sarfati, Tatiana, Sbisi, Noshalaza, Scheppers, Dihedile, Schultze-Strasser, Stephan, Schulze-Sturm, Ulf, Scott, Karen, Seeley, Janet, Serunjogi, Robert, Sewnarain, Leora, Shakeshaft, Clare, Sidhoo, Subashinie, Shibemba, Mercy, Shingadia, Delane, Singh, Sheleika, Sirirungsi, Wasna, Sithebe, Sibongile, Smit, Theresa, Smith, Kurt, Smuts, Marlize, Spyer, Moira, Sripaoraya, Worathip, Srirompotong, Ussanee, Srisuk, Warunee, Ssenyonga, Mark, Sudsaard, Patamawadee, Sukrakanchana, Praornsuda, Tearsansern, Pathanee, Teixeira, Carla, Than-in-at, Kanchana, Thapwai, Thitiwat, Thaweesombat, Yupawan, Thewsoongnoen, Jutarat, Thiébaut, Rodolphe, Thomason, Margaret, Thrasyvoulou, Laura, Thungkham, Khanungnit, Tikabibamu, Judith, Tinago, Gloria, Trairat, Ketmookda, Tudor-Williams, Gareth, Tukamushaba, Mercy, Tukwasibwe, Deogratiuos, Tumusiime, Julius, Tuna, Joana, Turkova, Anna, Turner, Rebecca, Udomvised, Arttasid, Vadee, Aasia, Van Huyssteen, Hesti, Van Looy, Nadine, Variava, Ebrahim, Vaughan-Gordon, Yvonne, Vecchia, Giulio, Violari, Avy, Vowden, Richard, Waalewijn, Hylke, Wampamba, Rebecca, Welch, Steve, Weller, Ian, Weza, Sibusisiwe, White, Ellen, White, Ian, Widuch, Kaja, Wilkes, Helen, Wimonklang, Sookpanee, Wynne, Ben, Yingyong, Pacharaporn, Nakawungu, Zaam Zinda, and Zuidewind, Peter

Abstract

Young children living with HIV have few treatment options. We aimed to assess the efficacy and safety of dolutegravir-based antiretroviral therapy (ART) in children weighing between 3 kg and less than 14 kg.

Published
2022
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34. COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

Author

Thygesen, Johan H, Tomlinson, Christopher, Hollings, Sam, Mizani, Mehrdad A, Handy, Alex, Akbari, Ashley, Banerjee, Amitava, Cooper, Jennifer, Lai, Alvina G, Li, Kezhi, Mateen, Bilal A, Sattar, Naveed, Sofat, Reecha, Torralbo, Ana, Wu, Honghan, Wood, Angela, Sterne, Jonathan A C, Pagel, Christina, Whiteley, William N, Sudlow, Cathie, Hemingway, Harry, Denaxas, Spiros, Abbasizanjani, Hoda, Ahmed, Nida, Ahmed, Badar, Akbari, Ashley, Akinoso-Imran, Abdul Qadr, Allara, Elias, Allery, Freya, Angelantonio, Emanuele Di, Ashworth, Mark, Ayyar-Gupta, Vandana, Babu-Narayan, Sonya, Bacon, Seb, Ball, Steve, Banerjee, Ami, Barber, Mark, Barrett, Jessica, Bennie, Marion, Berry, Colin, Beveridge, Jennifer, Birney, Ewan, Bojanić, Lana, Bolton, Thomas, Bone, Anna, Boyle, Jon, Braithwaite, Tasanee, Bray, Ben, Briffa, Norman, Brind, David, Brown, Katherine, Buch, Maya, Canoy, Dexter, Caputo, Massimo, Carragher, Raymond, Carson, Alan, Cezard, Genevieve, Chang, Jen-Yu Amy, Cheema, Kate, Chin, Richard, Chudasama, Yogini, Cooper, Jennifer, Copland, Emma, Crallan, Rebecca, Cripps, Rachel, Cromwell, David, Curcin, Vasa, Curry, Gwenetta, Dale, Caroline, Danesh, John, Das-Munshi, Jayati, Dashtban, Ashkan, Davies, Alun, Davies, Joanna, Davies, Gareth, Davies, Neil, Day, Joshua, Delmestri, Antonella, Denaxas, Spiros, Denholm, Rachel, Dennis, John, Denniston, Alastair, Deo, Salil, Dhillon, Baljean, Docherty, Annemarie, Dong, Tim, Douiri, Abdel, Downs, Johnny, Dregan, Alexandru, Ellins, Elizabeth A, Elwenspoek, Martha, Falck, Fabian, Falter, Florian, Fan, Yat Yi, Firth, Joseph, Fraser, Lorna, Friebel, Rocco, Gavrieli, Amir, Gerstung, Moritz, Gilbert, Ruth, Gillies, Clare, Glickman, Myer, Goldacre, Ben, Goldacre, Raph, Greaves, Felix, Green, Mark, Grieco, Luca, Griffiths, Rowena, Gurdasani, Deepti, Halcox, Julian, Hall, Nick, Hama, Tuankasfee, Handy, Alex, Hansell, Anna, Hardelid, Pia, Hardy, Flavien, Harris, Daniel, Harrison, Camille, Harron, Katie, Hassaine, Abdelaali, Hassan, Lamiece, Healey, Russell, Hemingway, Harry, Henderson, Angela, Herz, Naomi, Heyl, Johannes, Hidajat, Mira, Higginson, Irene, Hinchliffe, Rosie, Hippisley-Cox, Julia, Ho, Frederick, Hocaoglu, Mevhibe, Hollings, Sam, Horne, Elsie, Hughes, David, Humberstone, Ben, Inouye, Mike, Ip, Samantha, Islam, Nazrul, Jackson, Caroline, Jenkins, David, Jiang, Xiyun, Johnson, Shane, Kadam, Umesh, Kallis, Costas, Karim, Zainab, Kasan, Jake, Katsoulis, Michalis, Kavanagh, Kim, Kee, Frank, Keene, Spencer, Kent, Seamus, Khalid, Sara, Khawaja, Anthony, Khunti, Kamlesh, Killick, Richard, Kinnear, Deborah, Knight, Rochelle, Kolamunnage-Dona, Ruwanthi, Kontopantelis, Evan, Kurdi, Amanj, Lacey, Ben, Lai, Alvina, Lambarth, Andrew, Larzjan, Milad Nazarzadeh, Lawler, Deborah, Lawrence, Thomas, Lawson, Claire, Li, Qiuju, Li, Ken, Llinares, Miguel Bernabeu, Lorgelly, Paula, Lowe, Deborah, Lyons, Jane, Lyons, Ronan, Machado, Pedro, Macleod, Mary Joan, Macleod, John, Malgapo, Evaleen, Mamas, Mamas, Mamouei, Mohammad, Manohar, Sinduja, Mapeta, Rutendo, Martelli, Javiera Leniz, Martos, David Moreno, Mateen, Bilal, McCarthy, Aoife, Melville, Craig, Milton, Rebecca, Mizani, Mehrdad, Moncusi, Marta Pineda, Morales, Daniel, Mordi, Ify, Morrice, Lynn, Morris, Carole, Morris, Eva, Mu, Yi, Mueller, Tanja, Murdock, Lars, Nafilyan, Vahé, Nicholson, George, Nikiphorou, Elena, Nolan, John, Norris, Tom, Norris, Ruth, North, Laura, North, Teri-Louise, O'Connell, Dan, Oliver, Dominic, Oluyase, Adejoke, Olvera-Barrios, Abraham, Omigie, Efosa, Onida, Sarah, Padmanabhan, Sandosh, Palmer, Tom, Pasea, Laura, Patel, Riyaz, Payne, Rupert, Pell, Jill, Petitjean, Carmen, Pherwani, Arun, Pickrell, Owen, Pierotti, Livia, Pirmohamed, Munir, Priedon, Rouven, Prieto-Alhambra, Dani, Proudfoot, Alastair, Quinn, Terry, Quint, Jennifer, Raffetti, Elena, Rahimi, Kazem, Rao, Shishir, Razieh, Cameron, Roberts, Brian, Rogers, Caroline, Rossdale, Jennifer, Salim, Safa, Samani, Nilesh, Sattar, Naveed, Schnier, Christian, Schwartz, Roy, Selby, David, Seminog, Olena, Shabnam, Sharmin, Shah, Ajay, Shelton, Jon, Sheppard, James, Sinha, Shubhra, Skrypak, Mirek, Slapkova, Martina, Sleeman, Katherine, Smith, Craig, Sofat, Reecha, Sosenko, Filip, Sperrin, Matthew, Steeg, Sarah, Sterne, Jonathan, Stoica, Serban, Sudell, Maria, Sudlow, Cathie, Sun, Luanluan, Suseeladevi, Arun Karthikeyan, Sweeting, Michael, Sydes, Matt, Takhar, Rohan, Tang, Howard, Thygesen, Johan, Tilston, George, Tochel, Claire, Toit, Clea du, Tomlinson, Christopher, Toms, Renin, Torabi, Fatemeh, Torralbo, Ana, Townson, Julia, Tufail, Adnan, Tungamirai, Tapiwa, Varma, Susheel, Vollmer, Sebastian, Walker, Venexia, Wang, Tianxiao, Wang, Huan, Warwick, Alasdair, Watkinson, Ruth, Watson, Harry, Whiteley, William, Whittaker, Hannah, Wilde, Harry, Wilkinson, Tim, Williams, Gareth, Williams, Michelle, Williams, Richard, Withnell, Eloise, Wolfe, Charles, Wood, Angela, Wright, Lucy, Wu, Honghan, Wu, Jinge, Wu, Jianhua, Yates, Tom, Zaccardi, Francesco, Zhang, Haoting, Zhang, Huayu, and Zuccolo, Luisa

Abstract

Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework.

Published
2022
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38. MRI CHANGES FOLLOWING TREATMENT OF GLP‐1 ANALOGUE, LIRAGLUTIDE IN ALZHEIMER'S DISEASE.

Author

Edison, Paul, Femminella, Grazia Daniela, Ritchie, Craig, Nowell, Joseph, Holmes, Clive, Walker, Zuzana, Ridha, Basil H, Williams, Gareth, Lawrence, Robert M, McFarlane, Brady, Archer, Hilary, Coulthard, Elizabeth, Underwood, Benjamin, Koranteng, Paul, Karim, Salman, Perneczky, Robert, Prasanna, Aparna, Junaid, Kehinde, McGuinness, Bernadette, and Nilforooshan, Ramin

Abstract

Background: Preclinical evidence in transgenic models of Alzheimer's disease (AD) suggests that liraglutide, a GLP1 analogue, exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and reducing insulin resistance, and increasing the proliferation of neuronal progenitor cells. ELAD is a 12‐month, multi‐centre, randomised, double‐blind, placebo‐controlled, phase IIb trial of liraglutide in participants with mild to moderate AD conducted at 24 centres in the UK. Method: As a part of this study, a total of 204 Alzheimer's participants were randomised to receive either liraglutide or placebo as a daily subcutaneous injection for 12 months. All subjects underwent volumetric MRI scans at baseline and during follow up. Volumetric changes from baseline to follow up in MRI scans were evaluated using both regional volume analysis and voxel based morphometric analysis Result: MRI analysis demonstrated that temporal lobe volume, total grey matter volume and frontoparietal volume change was lower in liraglutide treated patients compared to the placebo group. Voxel based morphometry (VBM) analysis demonstrated that liraglutide‐treated participants showed a slower reduction in whole cortical grey matter, frontal, temporal and parietal lobe volume in participants treated with liraglutide compared to placebo. Conclusion: In the ELAD study, participants with mild to moderate AD who received liraglutide had slower reduction in MRI volume and cognition compared to the placebo demonstrating a potential benefit of liraglutide in the treatment of Alzheimer's disease. These findings highlight the potential of GLP‐1 analogues in the treatment of Alzheimer's disease [ABSTRACT FROM AUTHOR]

Published
2023
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40. Prehospital point-of-care biomarkers: missing link in acute myocardial infarction?

Author

Williams, Gareth Vaughan

Abstract

Coronary heart disease is a leading cause of death worldwide. Paramedics are instrumental in the treatment, triage and transport of patients experiencing acute coronary syndromes and acute myocardial infarction (AMI). Paramedics currently rely on prehospital electrocardiography and patient symptomology to diagnose AMI, which may result in missed diagnoses. Point-of-care biomarkers such as cardiac troponin (cTnT) and copeptin may have the potential to increase the diagnostic capabilities of prehospital providers. Multiple electronic databases (MAG Online Library, Cochrane Library, PubMed and Embase) were searched to evaluate the feasibility and potential application of cardiac biomarkers cTnT and copeptin in the prehospital setting. Because of the paucity of evidence, this article explores the evidence on the dual-marker strategy of cTnT and copeptin to increase diagnostic capabilities of prehospital providers, and as an adjunct for decision-making and risk stratification for AMI. The evidence suggests that using the combined dual-marker strategy of cTnT and copeptin may counteract limitations of the ‘troponin-blind’ period of cTnT and the low cardiac specificity of copeptin. However, the research for this method is still in its infancy and requires investigation into its feasibility and affordability as well as into the training required to implement it in paramedic practice.

Published
2022
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41. Robust HIV-specific CD4+and CD8+T-cell responses distinguish elite control in adolescents living with HIV from viremic nonprogressors

Author

Vieira, Vinicius A., Millar, Jane, Adland, Emily, Muenchhoff, Maximilian, Roider, Julia, Guash, Claudia Fortuny, Peluso, Denise, Thomé, Beatriz, Garcia-Guerrero, Maria C., Puertas, Mari C., Bamford, Alasdair, Brander, Christian, Carrington, Mary, Martinez-Picado, Javier, Frater, John, Tudor-Williams, Gareth, and Goulder, Philip

Abstract

Supplemental Digital Content is available in the text

Published
2022
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42. Evaluation of liraglutide in the treatment of Alzheimer's disease.

Author

Edison, Paul, Femminella, Grazia Daniela, Ritchie, Craig W., Holmes, Clive, Walker, Zuzana, Ridha, Basil H, Raza, Sanara, Livingston, Nicholas R, Nowell, Joseph, Busza, Gail, Frangou, Eleni, Love, Sharon, Williams, Gareth, Lawrence, Robert M, McFarlane, Brady, Archer, Hilary, Coulthard, Elizabeth, Underwood, Ben, Koranteng, Paul, and Karim, Salman

Abstract

Background: Liraglutide is a glucagon‐like peptide‐1 (GLP‐1) analogue licensed for the treatment of type 2 diabetes. Preclinical evidence in transgenic models of Alzheimer's disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells. Methods: ELAD is a 12‐month, multi‐centre, randomised, double‐blind, placebo‐controlled, phase IIb trial of liraglutide in participants with mild to moderate Alzheimer's dementia, conducted at several centres in the UK – (NCT01843075). [18F]FDG‐PET and MRI brain scans of all patients will be performed at baseline and after 12 months treatment with liraglutide or matching placebo. Once enrolled, all subjects had a neuropsychological battery of tests All scans and tests will be repeated after 12 months. A total of 204 participants were randomised to receive either liraglutide or placebo as a daily subcutaneous injection for 12 months. The primary objective was to evaluate the change in cerebral glucose metabolic rate in the cortical regions (hippocampus, medial temporal lobe, and posterior cingulate) from baseline to 12‐month follow‐up in participants with Alzheimer's disease receiving treatment with liraglutide compared to those receiving placebo. The key secondary outcomes were the change from baseline to 12 months in z scores for clinical and cognitive measures (Alzheimer's Disease Assessment Scale – Cognitive Subscale and Executive domain scores of the Neuropsychological Test Battery, Clinical Dementia Rating Sum of Boxes, and Alzheimer's Disease Cooperative Study – Activities of Daily Living) and the incidence and severity of treatment‐emergent adverse events or clinically important changes in safety assessments. Other secondary outcomes were 12‐month change in magnetic resonance imaging volume, diffusion tensor imaging parameters, and changes in composite scores using support machine vector analysis in the treatment group compared with the placebo group. Results: The study demonstrated that liraglutide treated patients performed significantly better than placebo arm in temporal lobe and whole cortical MRI volume and cognitive function measured by ADAS‐EXEC (ADAS‐Cog with Executive domains of the Neuropsychological Test Battery). Conclusion: This demonstrates that GLP1 analogues can improve cognitive function and MRI volume in AD subjects and could be a potential treatment for treatment for Alzheimer's [ABSTRACT FROM AUTHOR]

Published
2021
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43. Thermo-responsive nano-in-micro particles for MRI-guided chemotherapy

Author

Zhang, Ziwei, Wang, Yuexin, Rizk, Marwa M.I., Liang, Ruizheng, Wells, Connor J.R., Gurnani, Pratik, Zhou, Fenglei, Davies, Gemma-Louise, and Williams, Gareth R.

Abstract

In this work, we develop nano-in-micro thermo-responsive microspheres as theranostic systems for anti-cancer hyperthermia. Firstly, layered double hydroxide (LDH) nanoparticles were synthesized and subsequently loaded with the chemotherapeutic agents methotrexate (MTX) or 5-fluorouracil (5FU). The drug-loaded LDH particles were then co-encapsulated with superparamagnetic iron oxide nanoparticles (SPIONs) into poly(acrylamide-co-acrylonitrile) microparticles viaspray drying. The SPIONs are able to act as MRI contrast agents, thus resulting in potential theranostic formulations. Concave microparticles were observed by electron microscopy, and elemental mapping results suggest the LDH and SPION particles were homogeneously distributed inside the microparticles. In vitrodissolution tests showed that the drug was released over a prolonged period of time with the microspheres having distinct release curves at 37 and 43 °C. The relaxivity (r2) profiles were also found to be different over the temperature range 35 to 46 °C. Mathematical relationships between r2, release and temperature data were established, demonstrating that the microparticles have the potential for use in MRI-guided therapy. In vitrocell experiments revealed that the formulations permit synergistic hyperthermia-aided chemotherapy in cultured Caco-2 and A549 cells. Thus, the microparticles prepared in this work have potential as smart stimuli-responsive theranostics for hyperthermia-aided chemotherapy.

Published
2024
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45. Biocompatible hydroxy double salt tablet formulations

Author

Kaassis, Abdessamad Y.A. and Williams, Gareth R.

Abstract

Generally, commercial extended release tablets are core-based, which can cause problems for certain patients if they split them prior to ingestion. There is a need to develop non-core-based extended release tablets. We have previously reported the synthesis of two new biocompatible hydroxy double salts (HDSs), [Mg2Zn3(OH)8]Cl2⋅3.4H2O (MgZn–Cl) and [Fe2.4Zn2.6(OH)8]Cl2⋅2H2O (FeZn–Cl) (J. Mater. Chem. B 2016, 4, 5789), and found them to be good candidates for the extended release of diclofenac (Dic), ibuprofen (SI) and valproate (Val) (Appl. Clay. Sci. 2022, 221, 106456). Here we build on these previous results and report scale-up synthesis of MgZn–Cl and FeZn–Cl loaded with Dic, SI, and Val. The scaled-up products were blended with excipients and formulated into non-core based tablets. The post-compression parameters of the HDS-based tablets were assessed against the pharmacopeia requirements (friability, weight, and dose uniformity) and all passed the tests. Drug release studies were carried out using the paddle method (USPII) in conditions representative of the gastrointestinal tract. The HDS tablets were found to meet the pharmacopeia requirements for modified release dosage forms and showed similar release profiles to current commercial formulations. It is thus possible to develop modified release non-core based tablets using HDSs. These have additional benefits over standard commercial tablets, because the presence of the essential elements Zn, Fe and/or Mg in the layers can compensate for deficiencies induced over long-term treatment, and enhance therapeutic efficacy in some cases. Furthermore, the buffering effect of the HDS layers has the potential to prevent the gastric irritation often associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs).

Published
2023
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46. Ciprofloxacin-loaded electrospun nanofibres for antibacterial wound dressings

Author

Ju, Tian, Gaisford, Simon, and Williams, Gareth R.

Abstract

A wound is an injury that damages the normal structure and function of the skin and the underlying tissue. Disruption of the wound healing process causes chronic wounds, which are usually associated with microbial infections. In this work, ciprofloxacin was loaded into electrospun nanofibres to generate antibacterial wound dressings. Electrospun nanofibres are suitable for wound dressings due to their adaptability to the wound contour, high porosity for gas exchange, and a high surface area for absorbing wound exudate. Ciprofloxacin was successfully incorporated in polyvinyl alcohol (PVA) and PVA/alginate-blended electrospun nanofibres, with mean diameters ranging from 258 to 460 nm. The materials were characterized using differential scanning calorimetry (DSC) and X-ray diffraction (XRD) to examine the thermal properties and physical forms of the drug and polymers. Fourier transform infrared spectroscopy (FTIR) was used to characterise intermolecular interactions within the materials. DSC thermograms showed all the fibres have a PVA enthalpy relaxation peak at 47 °C and a PVA melting endotherm at 229 °C. The XRD patterns indicated decreased crystallinity of PVA after electrospinning. No crystalline drug could be detected in the fibres by either XRD or DSC. FTIR spectra showed the formation of hydrogen bonds between PVA and alginate in the fibres. All the electrospun nanofibres have high water uptake capacity (190%–381%). The ciprofloxacin-loaded electrospun nanofibres also have high drug encapsulation efficiency, above 90%. The drug release profiles demonstrated controlled-release of the drug, following the Korsmeyer-Peppas model. The antibacterial efficacy of the nanofibres was evaluated by isothermal microcalorimetric assays, with the ciprofloxacin-loaded nanofibres found to exhibit equivalent antibacterial efficacy against Staphylococcus aureusand Pseudomonas aeruginosato pure ciprofloxacin. Hence, the fibres fabricated in this work have the potential to be used as advanced systems to prevent infection during wound healing.

Published
2023
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47. Impact of Decalcification, Cold Ischemia, and Deglycosylation on Performance of Programmed Cell Death Ligand-1 Antibodies with Different Binding Epitopes: Comparison of Seven Clones

Author

Lawson, Nicola L., Scorer, Paul W., Williams, Gareth H., Vandenberghe, Michel E., Ratcliffe, Marianne J., and Barker, Craig

Abstract

Programmed cell death ligand-1 (PD-L1) expression levels in patient tumors have demonstrated clinical utility across many cancer types and are used to determine treatment eligibility. Several independently developed PD-L1 immunohistochemical (IHC) predictive assays are commercially available and have demonstrated different levels of staining between assays, generating interest in understanding the similarities and differences between assays (1). Previously, we identified epitopes in the internal and external domains of PD-L1, bound by antibodies in routine clinical use (SP263, SP142, 22C3, and 28-8). Variance in performance of assays utilizing these antibodies, observed following exposure to pre-analytical factors such as decalcification, cold ischemia, and duration of fixation, encouraged additional investigation of antibody binding sites, to understand whether binding site structures/conformations contribute to differential PD-L1 IHC assay staining. We proceeded to further investigate the epitopes on PD-L1 bound by these antibodies, alongside the major clones utilized in laboratory-developed tests (E1L3N, QR1, 73-10). Characterization of QR1 and 73-10 clones demonstrated that both bind the PD-L1 C-terminal internal domain, similar to SP263/SP142. Our results also demonstrate that under sub-optimal decalcification or fixation conditions, the performance of internal domain antibodies is less detrimentally affected than that of external domain antibodies 22C3/28-8. Furthermore, we show that the binding sites of external domain antibodies are susceptible to deglycosylation and conformational structural changes which directly result in IHC staining reduction or loss. The binding sites of internal domain antibodies were unaffected by deglycosylation or conformational structural change. This study demonstrates that the location and conformation of binding sites, recognized by antibodies employed in PD-L1 diagnostic assays differ significantly and exhibit differing degrees of robustness. These findings should reinforce the need for vigilance when performing clinical testing with different PD-L1 IHC assays, particularly in the control of cold ischemia and the selection of fixation and decalcification conditions.

Published
2023
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49. Back Cover: Theranostics for MRI‐guided therapy: Recent developments (View 3/2022)

Author

Zhang, Ziwei, Zhou, Feng‐Lei, Davies, Gemma‐Louise, and Williams, Gareth R.

Abstract

In article number 20200134, Gareth Williams and coworkers have presented magnetic resonance imaging is a powerful method for imaging in vivoand hence for medical diagnosis. It can also be combined with anti‐cancer therapeutic agents to generate theranostics for simultaneous imaging and therapy.

Published
2022
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50. Theranostics for MRI‐guided therapy: Recent developments

Author

Zhang, Ziwei, Zhou, Feng‐Lei, Davies, Gemma‐Louise, and Williams, Gareth R.

Abstract

Recent advances in bioimaging, biochemistry, and bioinformatics have facilitated the development of personalized and precision medicine. Theranostics, combining imaging modalities and therapeutic agents, have garnered a lot of attention in this context, owing to their potential to monitor and control treatment for individual patients. A promising strategy to achieve this goal involves the development of therapy guided by magnetic resonance imaging (MRI). MRI has a high degree of soft tissue contrast, low invasiveness, high depth of penetration and good spatial resolution. MRI‐guided therapy could thus allow precise and time‐resolved assessment of disease conditions and therapeutic progression. This article will give a brief introduction to the principles of MRI, and describe recently developed strategies to produce MRI‐guided therapies. A number of theranostics based on T1, T2, or chemical exchange saturation transfer (CEST) MRI have been explored to track the route of drug carriers in vivo and image diseased tissue so as to enhance bioavailability, overcome complex delivery barriers, and assess therapeutic responses. In addition, the integration of thermal therapy and MRI imaging offers a strategy to noninvasively identify target areas, plan treatment, and provide real‐time assessment of the efficacy of tumor ablation. We also discuss advances in intelligent nanoparticles combining small molecule drugs, thermal treatment and multimodal imaging, arguing that these multifunctional agents can further improve therapeutic outcomes. This paper first describes the theory of MRI and its utility for imaging in vivo. It then reviews recently developed theranostics combining MRI‐based diagnosis (e.g., T1/T2, CEST MRI) and an anticancer therapeutic agent for applications in chemotherapy and thermal therapies.

Published
2022
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