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1. Using Community-Based Interventions to Reduce Public Stigma of Children with Disabilities: A Feasibility Study

Author

Hepperlen, Renee A., Biggs, Jennifer, Mwandileya, Watson, Rabaey, Paula, Ngulube, Esther, and Hearst, Mary O.

Abstract

Background: Public stigma, or negative community-held beliefs, about children with disabilities (CWDs) often leads to negative outcomes for CWD and their families. This study considers the effectiveness of four community-level interventions to reduce public stigma in two Lusaka, Zambia communities. Methods: This feasibility study describes four community-based interventions to provide education to consider whether perceptions of attitudes and stigma towards CWD changed after implementing four educational interventions. Results: Results revealed that these interventions were achievable. Preliminary multiple regression analyses indicated a significant impact of attending an event on the attitude scale, while no effect on the stigma scale. Presence at multiple anti-stigma events exhibited no effect for the stigma scale, while the attitude scale showed significance. Discussion: This study builds on the limited research available in low-income countries to reduce public stigma towards CWD, with the hope of enhance quality of life for CWD and their families.

Published
2021
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5. The Impact of Level of Physical Therapist Assistant Involvement on Patient Outcomes Following Stroke

Author

Biggs, Jennifer

Subjects
Stroke (Disease) -- Care and treatment -- Patient outcomes, Medical assistants -- Practice, Physical therapists -- Practice, Health
Abstract

Objective. This study investigates if higher utilization of physical therapist assistants adversely affects patient outcomes in the acute rehabilitation setting for patients following a cerebrovascular accident (CVA). Methods. Participants were admitted to 1 of 5 inpatient rehabilitation facilities following a CVA from 2008 to 2010. High physical therapist assistant use was defined as [greater than or equal to]20% of the physical therapist visits being provided by the physical therapist assistant for an episode of care. Multivariable regression techniques examined differences in functional outcome, discharge location, and length of stay between high and low physical therapist assistant use groups. Propensity scoring methods supplemented findings of the regression analyses. Results. Of the 1561 participants, 496 (32%) had high physical therapist assistant involvement. Baseline participant characteristics such as age, sex, baseline motor function, and comorbidities did not differ between high and low physical therapist assistant use groups. After adjusting for patient characteristics, rehabilitation facility, and year, higher physical therapist assistant use did not adversely affect functional outcome or length of stay. Fewer conclusions can be drawn regarding discharge location, although there was no significant difference in discharge location between groups with high and low physical therapist assistant utilization. Propensity scoring methods supported the findings of the regression analyses. Conclusions. Higher physical therapist assistant involvement in the rehabilitation of patients following CVA did not adversely affect functional outcome, increase length of stay, or reduce the likelihood of discharge to home from an inpatient rehabilitation facility. Impact. The results demonstrate the value of the physical therapist assistant in the provision of physical therapy for patients with stroke in the inpatient rehabilitation setting. Higher involvement of the physical therapist assistant may provide cost savings while maintaining patient outcomes for this setting and population., Physical therapist services are provided by physical therapists as well as by physical therapist assistants, who are the only additional providers educated to implement selected physical therapist interventions. (1) As [...]

Published
2020

7. Data from Tracking the Genomic Evolution of Esophageal Adenocarcinoma through Neoadjuvant Chemotherapy

Author

Murugaesu, Nirupa, primary, Wilson, Gareth A., primary, Birkbak, Nicolai J., primary, Watkins, Thomas B.K., primary, McGranahan, Nicholas, primary, Kumar, Sacheen, primary, Abbassi-Ghadi, Nima, primary, Salm, Max, primary, Mitter, Richard, primary, Horswell, Stuart, primary, Rowan, Andrew, primary, Phillimore, Benjamin, primary, Biggs, Jennifer, primary, Begum, Sharmin, primary, Matthews, Nik, primary, Hochhauser, Daniel, primary, Hanna, George B., primary, and Swanton, Charles, primary

Published
2023
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8. Supplementary Table S3 from Tracking the Genomic Evolution of Esophageal Adenocarcinoma through Neoadjuvant Chemotherapy

Author

Murugaesu, Nirupa, primary, Wilson, Gareth A., primary, Birkbak, Nicolai J., primary, Watkins, Thomas B.K., primary, McGranahan, Nicholas, primary, Kumar, Sacheen, primary, Abbassi-Ghadi, Nima, primary, Salm, Max, primary, Mitter, Richard, primary, Horswell, Stuart, primary, Rowan, Andrew, primary, Phillimore, Benjamin, primary, Biggs, Jennifer, primary, Begum, Sharmin, primary, Matthews, Nik, primary, Hochhauser, Daniel, primary, Hanna, George B., primary, and Swanton, Charles, primary

Published
2023
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9. Supplementary Methods, Tables S1 - S2, S4, Figures S1 - S11 from Tracking the Genomic Evolution of Esophageal Adenocarcinoma through Neoadjuvant Chemotherapy

Author

Murugaesu, Nirupa, primary, Wilson, Gareth A., primary, Birkbak, Nicolai J., primary, Watkins, Thomas B.K., primary, McGranahan, Nicholas, primary, Kumar, Sacheen, primary, Abbassi-Ghadi, Nima, primary, Salm, Max, primary, Mitter, Richard, primary, Horswell, Stuart, primary, Rowan, Andrew, primary, Phillimore, Benjamin, primary, Biggs, Jennifer, primary, Begum, Sharmin, primary, Matthews, Nik, primary, Hochhauser, Daniel, primary, Hanna, George B., primary, and Swanton, Charles, primary

Published
2023
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10. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Author

Abbosh, Christopher, Birkbak, Nicolai J., Wilson, Gareth A., Jamal-Hanjani, Mariam, Constantin, Tudor, Salari, Raheleh, Le Quesne, John, Moore, David A., Veeriah, Selvaraju, Rosenthal, Rachel, Marafioti, Teresa, Kirkizlar, Eser, Watkins, Thomas B. K., McGranahan, Nicholas, Ward, Sophia, Martinson, Luke, Riley, Joan, Fraioli, Francesco, Al Bakir, Maise, Grnroos, Eva, Zambrana, Francisco, Endozo, Raymondo, Bi, Wenya Linda, Fennessy, Fiona M., Sponer, Nicole, Johnson, Diana, Laycock, Joanne, Shafi, Seema, Czyzewska-Khan, Justyna, Rowan, Andrew, Chambers, Tim, Matthews, Nik, Turajlic, Samra, Hiley, Crispin, Lee, Siow Ming, Forster, Martin D., Ahmad, Tanya, Falzon, Mary, Borg, Elaine, Lawrence, David, Hayward, Martin, Kolvekar, Shyam, Panagiotopoulos, Nikolaos, Janes, Sam M., Thakrar, Ricky, Ahmed, Asia, Blackhall, Fiona, Summers, Yvonne, Hafez, Dina, Naik, Ashwini, Ganguly, Apratim, Kareht, Stephanie, Shah, Rajesh, Joseph, Leena, Marie Quinn, Anne, Crosbie, Phil A., Naidu, Babu, Middleton, Gary, Langman, Gerald, Trotter, Simon, Nicolson, Marianne, Remmen, Hardy, Kerr, Keith, Chetty, Mahendran, Gomersall, Lesley, Fennell, Dean A., Nakas, Apostolos, Rathinam, Sridhar, Anand, Girija, Khan, Sajid, Russell, Peter, Ezhil, Veni, Ismail, Babikir, Irvin-Sellers, Melanie, Prakash, Vineet, Lester, Jason F., Kornaszewska, Malgorzata, Attanoos, Richard, Adams, Haydn, Davies, Helen, Oukrif, Dahmane, Akarca, Ayse U., Hartley, John A., Lowe, Helen L., Lock, Sara, Iles, Natasha, Bell, Harriet, Ngai, Yenting, Elgar, Greg, Szallasi, Zoltan, Schwarz, Roland F., Herrero, Javier, Stewart, Aengus, Quezada, Sergio A., Peggs, Karl S., Van Loo, Peter, Dive, Caroline, Lin, C. Jimmy, Rabinowitz, Matthew, Aerts, Hugo J. W. L., Hackshaw, Allan, Shaw, Jacqui A., Zimmermann, Bernhard G., Swanton, Charles, Bosshard-Carter, Leticia, Goh, Gerald, Gorman, Pat, Murugaesu, Nirupa, Hynds, Robert E., Horswell, Stuart, Bakir, Maise Al, Mitter, Richard, Escudero, Mickael, Xu, Hang, Goldman, Jacki, Stone, Richard Kevin, Denner, Tamara, Biggs, Jennifer, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Nye, Emma, Graca, Sofia, Joshi, Kroopa, Furness, Andrew, Ben Aissa, Assma, Wong, Yien Ning Sophia, Georgiou, Andy, Simeon, Celia, Hector, Gemma, Smith, Amy, Aranda, Marie, Novelli, Marco, Papadatos-Pastos, Dionysis, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Taylor, Magali, Choudhary, Junaid, Califano, Raffaele, Taylor, Paul, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Moss, Stuart, Idries, Faiza, Bishop, Paul, Chaturvedi, Anshuman, Quinn, Anne Marie, Doran, Helen, Leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Novasio, Juliette, Rogan, Jane, Smith, Elaine, Tugwood, Jonathan, Brady, Ged, Rothwell, Dominic G., Chemi, Francesca, Pierce, Jackie, Gulati, Sakshi, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Djearaman, Madava, Quesne, John Le, Thomas, Anne, Walter, Harriet, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Primrose, Lindsay, Amadi, Anita, Palmer, Shirley, Miller, Joy, Buchan, Keith, Edwards, Alison, Morgan, Fiona, Verjee, Azmina, MacKenzie, Mairead, Wilcox, Maggie, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Barbosa, Monica Tavares, Bowman, Alex, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Proli, Chiara, Cufari, Maria Elena, Ronquillo, John Carlo, Kwayie, Angela, Bhayani, Harshil, Hamilton, Morag, Bakar, Yusura, Mensah, Natalie, Ambrose, Lyn, Devaraj, Anand, Buderi, Silviu, Finch, Jonathan, Azcarate, Leire, Chavan, Hema, Green, Sophie, Mashinga, Hillaria, Nicholson, Andrew G., Lau, Kelvin, Sheaff, Michael, Schmid, Peter, Conibear, John, Light, Teresa, Horey, Tracey, Danson, Sarah, Bury, Jonathan, Edwards, John, Hill, Jennifer, Matthews, Sue, Kitsanta, Yota, Suvarna, Kim, Fisher, Patricia, Keerio, Allah Dino, Shackcloth, Michael, Gosney, John, Postmus, Pieter, Feeney, Sarah, Asante-Siaw, Julius, Dentro, Stefan, and Dessimoz, Christophe

Subjects
Lung cancer -- Genetic aspects -- Development and progression, DNA sequencing -- Methods, Phylogeny -- Observations, Cancer metastasis -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies., Author(s): Christopher Abbosh [1]; Nicolai J. Birkbak [1, 2]; Gareth A. Wilson [1, 2]; Mariam Jamal-Hanjani [1]; Tudor Constantin [3]; Raheleh Salari [3]; John Le Quesne [4]; David A. Moore [...]

Published
2017
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19. Aligning a training curriculum with local needs: Use of an advisory board.

Author

Hepperlen, Renee A, Rabaey, Paula, Ngulube, Esther, Biggs, Jennifer, DeGracia, Donna, and Hearst, Mary O

Subjects
SOCIAL support, MIDDLE-income countries, STAKEHOLDER analysis, CHILDREN with disabilities, DEVELOPMENTAL disabilities, SOCIAL stigma, LOW-income countries, INTERPROFESSIONAL relations, CURRICULUM planning, PEOPLE with intellectual disabilities, PROCEDURE manuals, THEMATIC analysis
Abstract

Children with disabilities and their families often experience life circumstances that lead to reduced quality of life in low- and middle-income countries. This article describes the development of a curriculum to train community volunteers to provide support to families of children with disabilities in Lusaka, Zambia, using feedback from an advisory board of local stakeholders. Stakeholders had two opportunities to offer input on the curriculum. Reviewer comments focused on three themes – making the manual more Zambian, needing additional content, and simplifying the message. Recommendations were incorporated into the manual – allowing for culturally appropriate alignment with Zambian needs and customs. [ABSTRACT FROM AUTHOR]

Published
2022
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22. Community-based intervention to reduce stigma for children with disabilities in Lusaka, Zambia: a pilot.

Author

Hearst, Mary O., Adelli, Rakesh, Hepperlen, Renee, Biggs, Jennifer, DeGracia, Donna, Ngulube, Esther, Maluskiku-Mwewa, Batuke, Johnson, Dana E., and Rabaey, Paula

Subjects
PILOT projects, HEALTH education, PSYCHOLOGY of children with disabilities, SOCIAL support, EVALUATION of human services programs, HOME care services, SOCIAL stigma, COMMUNITY health services, MEDICAL personnel, FAMILY-centered care, FAMILY attitudes, PATIENTS' families, PRE-tests & post-tests, RESEARCH funding, REHABILITATION, PATIENT-professional relations, PLAY therapy, PUBLIC opinion
Abstract

This pilot intervention aims to reduce stigma towards children with disabilities living in family-based care. Kusamala + is a pre-post evaluation of a pilot community-based intervention in two low-income compounds in Lusaka, Zambia. Door-to-door canvassing and community referrals were used to identify and enroll children with disabilities. Parents/guardians and community members completed surveys regarding stigma and support. Health professionals supervised, trained, and provided ongoing support for 2–3 community caregivers (CCGs). CCG's provided home-based education, referrals, playgroups, and social support for 20–25 families each. Community events were held at health facilities, churches and community spaces to reduce community-level stigma towards children with disabilities. Staff identified 632 children with disabilities. Staff completed over 4500 home visits, 288 children joined playgroups, made 775 referrals, and over 23,000 attended community sensitization events. Longitudinal data was available for 129 families with a child with a disability. Over one year, families and community members reported less perceived rejection by family and peers but less agreement that children with disabilities should be treated the same as other children. Kusamala + was a feasible, acceptable and broad reach with limited program impact. Future work will incorporate lessons learned with a focus on sustainability and scalability. Children with disability are often hidden and isolated in low- and middle-income countries (LMIC), particularly in low-resource communities. Stigma towards children with disabilities continues in LMIC and further reduces that child's ability to engage fully in social and civic life. Community- and home-based programming is a feasible and acceptable approach to engaging with community and families with a child with a disability. The identification and referral of additional children with disabilities to physiotherapy and other government services can provide additional strain on already limited resources. Once a pilot program is deemed acceptable and feasible, any further design planning must include considerations for sustainability and scalability. System strengthening is a key component of sustainability and scalability to ensure success in planning, implementation, monitoring and evaluation. [ABSTRACT FROM AUTHOR]

Published
2022
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25. Fidelity_table – Supplemental material for Optimized Sleep After Brain Injury (OSABI): A Pilot Study of a Sleep Hygiene Intervention for Individuals With Moderate to Severe Traumatic Brain Injury

Author

Makley, Michael J., Gerber, Don, Newman, Jody K., Philippus, Angie, Monden, Kimberley R., Biggs, Jennifer, Spier, Eric, Tarwater, Patrick, and Weintraub, Alan

Subjects
FOS: Clinical medicine, 110308 Geriatrics and Gerontology, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, Fidelity_table for Optimized Sleep After Brain Injury (OSABI): A Pilot Study of a Sleep Hygiene Intervention for Individuals With Moderate to Severe Traumatic Brain Injury by Michael J. Makley, Don Gerber, Jody K. Newman, Angie Philippus, Kimberley R. Monden, Jennifer Biggs, Eric Spier, Patrick Tarwater and Alan Weintraub in Neurorehabilitation and Neural Repair

Published
2019
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26. Modified_STOP_BANG_QUESTIONNAIRE – Supplemental material for Optimized Sleep After Brain Injury (OSABI): A Pilot Study of a Sleep Hygiene Intervention for Individuals With Moderate to Severe Traumatic Brain Injury

Author

Makley, Michael J., Gerber, Don, Newman, Jody K., Philippus, Angie, Monden, Kimberley R., Biggs, Jennifer, Spier, Eric, Tarwater, Patrick, and Weintraub, Alan

Subjects
FOS: Clinical medicine, 110308 Geriatrics and Gerontology, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, Modified_STOP_BANG_QUESTIONNAIRE for Optimized Sleep After Brain Injury (OSABI): A Pilot Study of a Sleep Hygiene Intervention for Individuals With Moderate to Severe Traumatic Brain Injury by Michael J. Makley, Don Gerber, Jody K. Newman, Angie Philippus, Kimberley R. Monden, Jennifer Biggs, Eric Spier, Patrick Tarwater and Alan Weintraub in Neurorehabilitation and Neural Repair

Published
2019
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27. OSABI_INCLUSION_AND_EXCLUSION_CRITERIA – Supplemental material for Optimized Sleep After Brain Injury (OSABI): A Pilot Study of a Sleep Hygiene Intervention for Individuals With Moderate to Severe Traumatic Brain Injury

Author

Makley, Michael J., Gerber, Don, Newman, Jody K., Philippus, Angie, Monden, Kimberley R., Biggs, Jennifer, Spier, Eric, Tarwater, Patrick, and Weintraub, Alan

Subjects
FOS: Clinical medicine, 110308 Geriatrics and Gerontology, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, OSABI_INCLUSION_AND_EXCLUSION_CRITERIA for Optimized Sleep After Brain Injury (OSABI): A Pilot Study of a Sleep Hygiene Intervention for Individuals With Moderate to Severe Traumatic Brain Injury by Michael J. Makley, Don Gerber, Jody K. Newman, Angie Philippus, Kimberley R. Monden, Jennifer Biggs, Eric Spier, Patrick Tarwater and Alan Weintraub in Neurorehabilitation and Neural Repair

Published
2019
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28. Sleep_Hygiene_Protocol_Questionaire-Family_Member – Supplemental material for Optimized Sleep After Brain Injury (OSABI): A Pilot Study of a Sleep Hygiene Intervention for Individuals With Moderate to Severe Traumatic Brain Injury

Author

Makley, Michael J., Gerber, Don, Newman, Jody K., Philippus, Angie, Monden, Kimberley R., Biggs, Jennifer, Spier, Eric, Tarwater, Patrick, and Weintraub, Alan

Subjects
FOS: Clinical medicine, 110308 Geriatrics and Gerontology, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, Sleep_Hygiene_Protocol_Questionaire-Family_Member for Optimized Sleep After Brain Injury (OSABI): A Pilot Study of a Sleep Hygiene Intervention for Individuals With Moderate to Severe Traumatic Brain Injury by Michael J. Makley, Don Gerber, Jody K. Newman, Angie Philippus, Kimberley R. Monden, Jennifer Biggs, Eric Spier, Patrick Tarwater and Alan Weintraub in Neurorehabilitation and Neural Repair

Published
2019
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29. CONSORT_2010_Checklist_OSABI_2019 – Supplemental material for Optimized Sleep After Brain Injury (OSABI): A Pilot Study of a Sleep Hygiene Intervention for Individuals With Moderate to Severe Traumatic Brain Injury

Author

Makley, Michael J., Gerber, Don, Newman, Jody K., Philippus, Angie, Monden, Kimberley R., Biggs, Jennifer, Spier, Eric, Tarwater, Patrick, and Weintraub, Alan

Subjects
FOS: Clinical medicine, 110308 Geriatrics and Gerontology, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, CONSORT_2010_Checklist_OSABI_2019 for Optimized Sleep After Brain Injury (OSABI): A Pilot Study of a Sleep Hygiene Intervention for Individuals With Moderate to Severe Traumatic Brain Injury by Michael J. Makley, Don Gerber, Jody K. Newman, Angie Philippus, Kimberley R. Monden, Jennifer Biggs, Eric Spier, Patrick Tarwater and Alan Weintraub in Neurorehabilitation and Neural Repair

Published
2019
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30. Nursing_Staff_Feasibility_Questionnaire – Supplemental material for Optimized Sleep After Brain Injury (OSABI): A Pilot Study of a Sleep Hygiene Intervention for Individuals With Moderate to Severe Traumatic Brain Injury

Author

Makley, Michael J., Gerber, Don, Newman, Jody K., Philippus, Angie, Monden, Kimberley R., Biggs, Jennifer, Spier, Eric, Tarwater, Patrick, and Weintraub, Alan

Subjects
FOS: Clinical medicine, 110308 Geriatrics and Gerontology, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, Nursing_Staff_Feasibility_Questionnaire for Optimized Sleep After Brain Injury (OSABI): A Pilot Study of a Sleep Hygiene Intervention for Individuals With Moderate to Severe Traumatic Brain Injury by Michael J. Makley, Don Gerber, Jody K. Newman, Angie Philippus, Kimberley R. Monden, Jennifer Biggs, Eric Spier, Patrick Tarwater and Alan Weintraub in Neurorehabilitation and Neural Repair

Published
2019
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31. Sleep_Hygiene_Protocol_Questionnaire-Participant – Supplemental material for Optimized Sleep After Brain Injury (OSABI): A Pilot Study of a Sleep Hygiene Intervention for Individuals With Moderate to Severe Traumatic Brain Injury

Author

Makley, Michael J., Gerber, Don, Newman, Jody K., Philippus, Angie, Monden, Kimberley R., Biggs, Jennifer, Spier, Eric, Tarwater, Patrick, and Weintraub, Alan

Subjects
FOS: Clinical medicine, 110308 Geriatrics and Gerontology, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, Sleep_Hygiene_Protocol_Questionnaire-Participant for Optimized Sleep After Brain Injury (OSABI): A Pilot Study of a Sleep Hygiene Intervention for Individuals With Moderate to Severe Traumatic Brain Injury by Michael J. Makley, Don Gerber, Jody K. Newman, Angie Philippus, Kimberley R. Monden, Jennifer Biggs, Eric Spier, Patrick Tarwater and Alan Weintraub in Neurorehabilitation and Neural Repair

Published
2019
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38. Modification of a modulated arc total body irradiation technique: Implementation and first clinical experience for paediatric patients

Author

Pemberton, Melanie, Brady, Carole, Taylor, Beth, Tyrrell, Danielle, Sim, Lucy, Zawlodzka-Bednarz, Sylwia, Biggs, Jennifer, Peters, Mitchell, Baines, John, Hargrave, Cathy, Pemberton, Melanie, Brady, Carole, Taylor, Beth, Tyrrell, Danielle, Sim, Lucy, Zawlodzka-Bednarz, Sylwia, Biggs, Jennifer, Peters, Mitchell, Baines, John, and Hargrave, Cathy

Abstract

Introduction To implement the modulated arc total body irradiation (MATBI) technique within the existing infrastructure of a radiation oncology department. The technique needed to treat paediatric patients of all ages, some of whom would require general anaesthesia (GA). Methods The MATBI technique required minor modifications to be incorporated within existing departmental infrastructure. Ancillary equipment essential to the technique were identified and in some cases custom designed to meet health and safety criteria. GA equipment was also considered. To evaluate the effectiveness of the implemented technique, an audit of the cases clinically treated was conducted. Results A motorised treatment couch was designed to allow the patient to be positioned in stabilisation equipment at a height, then lowered to the floor to accommodate source‐to‐skin‐distances from 180 cm to 198 cm to treat the fixed 40 cm × 40 cm field size. Treatment couch design also facilitated positioning of the bespoke two‐part spoiler. While organ at risk dose is limited using a beam weight optimisation technique, the dose is further reduced using compensators placed close to the patient's skin on a 3D printed custom‐made support bridge. A digital radiography system is used to verify compensator position. Fifteen patients have been treated to date for various diseases using a variety of dose fractionations ranging from 2 Gy in a single fraction to 12 Gy in 6 fractions. Five patients have required GA due to age or behavioural issues. Conclusion The modified MATBI technique and the equipment required for treatment delivery has been found to be well tolerated by all patients.

Published
2018

39. Fc-Optimized Anti-CD25 depletes tumor-infiltrating regulatory T Cells and synergizes with PD-1 Blockade to eradicate established tumors

Author

Arce Vargas, Frederick, Furness, Andrew J.S., Solomon, Isabelle, Joshi, Kroopa, Mekkaoui, Leila, Lesko, Marta H., Miranda Rota, Enrique, Dahan, Rony, Georgiou, Andrew, Sledzinska, Anna, Ben Aissa, Assma, Franz, Dafne, Werner Sunderland, Mariana, Wong, Yien Ning Sophia, Henry, Jake Y., O’Brien, Tim, Nicol, David, Challacombe, Ben, Beers, Stephen A., Turajlic, Samra, Gore, Martin, Larkin, James, Swanton, Charles, Chester, Kerry A., Pule, Martin, Ravetch, Jeffrey V., Marafioti, Teresa, Peggs, Karl S., Quezada, Sergio A., Spain, Lavinia, Wotherspoon, Andrew, Francis, Nicholas, Smith, Myles, Strauss, Dirk, Hayes, Andrew, Soultati, Aspasia, Stares, Mark, Lynch, Joanna, Fotiadis, Nicos, Fernando, Archana, Hazell, Steve, Chandra, Ashish, Pickering, Lisa, Rudman, Sarah, Chowdhury, Simon, Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Shafi, Seema, Czyzewska-Khan, Justyna, Johnson, Diana, Laycock, Joanne, Bosshard-Carter, Leticia, Goh, Gerald, Rosenthal, Rachel, Gorman, Pat, Murugaesu, Nirupa, Hynds, Robert E., Wilson, Gareth, Birkbak, Nicolai J., Watkins, Thomas B.K., McGranahan, Nicholas, Horswell, Stuart, Mitter, Richard, Escudero, Mickael, Stewart, Aengus, Van Loo, Peter, Rowan, Andrew, Xu, Hang, Hiley, Crispin, Abbosh, Christopher, Goldman, Jacki, Stone, Richard Kevin, Denner, Tamara, Matthews, Nik, Elgar, Greg, Ward, Sophia, Biggs, Jennifer, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Chambers, Tim, Nye, Emma, Graca, Sofia, Al Bakir, Maise, Hartley, John A., Lowe, Helen L., Herrero, Javier, Lawrence, David, Hayward, Martin, Panagiotopoulos, Nikolaos, Kolvekar, Shyam, Falzon, Mary, Borg, Elaine, Simeon, Celia, Hector, Gemma, Smith, Amy, Aranda, Marie, Novelli, Marco, Oukrif, Dahmane, Janes, Sam M., Thakrar, Ricky, Forster, Martin, Ahmad, Tanya, Lee, Siow Ming, Papadatos-Pastos, Dionysis, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Ahmed, Asia, Taylor, Magali, Choudhary, Junaid, Summers, Yvonne, Califano, Raffaele, Taylor, Paul, Shah, Rajesh, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Crosbie, Phil, Moss, Stuart, Idries, Faiza, Joseph, Leena, Bishop, Paul, Chaturved, Anshuman, Quinn, Anne Marie, Doran, Helen, Leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Novasio, Juliette, Blackhall, Fiona, Rogan, Jane, Smith, Elaine, Dive, Caroline, Tugwood, Jonathan, Brady, Ged, Rothwell, Dominic G., Chemi, Francesca, Pierce, Jackie, Gulati, Sakshi, Naidu, Babu, Langman, Gerald, Trotter, Simon, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Middleton, Gary, Djearaman, Madava, Fennell, Dean, Shaw, Jacqui A., Le Quesne, John, Moore, David, Nakas, Apostolos, Rathinam, Sridhar, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Riley, Joan, Primrose, Lindsay, Martinson, Luke, Anand, Girija, Khan, Sajid, Amadi, Anita, Nicolson, Marianne, Kerr, Keith, Palmer, Shirley, Remmen, Hardy, Miller, Joy, Buchan, Keith, Chetty, Mahendran, Gomersall, Lesley, Lester, Jason, Edwards, Alison, Morgan, Fiona, Adams, Haydn, Davies, Helen, Kornaszewska, Malgorzata, Attanoos, Richard, Lock, Sara, Verjee, Azmina, MacKenzie, Mairead, Wilcox, Maggie, Bell, Harriet, Iles, Natasha, Hackshaw, Allan, Ngai, Yenting, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Barbosa, Monica Tavares, Bowman, Alex, Jorda, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Proli, Chiara, Cufari, Maria Elena, Ronquillo, John Carlo, Kwayie, Angela, Bhayani, Harshil, Hamilton, Morag, Bakar, Yusura, Mensah, Natalie, Ambrose, Lyn, Devaraj, Anand, Buderi, Silviu, Finch, Jonathan, Azcarate, Leire, Chavan, Hema, Green, Sophie, Mashinga, Hillaria, Nicholson, Andrew G., Lau, Kelvin, Sheaff, Michael, Schmid, Peter, Conibear, John, Ezhil, Veni, Ismail, Babikir, Irvin-sellers, Melanie, Prakash, Vineet, Russell, Peter, Light, Teresa, Horey, Tracey, Danson, Sarah, Bury, Jonathan, Edwards, John, Hill, Jennifer, Matthews, Sue, Kitsanta, Yota, Suvarna, Kim, Fisher, Patricia, Keerio, Allah Dino, Shackcloth, Michael, Gosney, John, Postmus, Pieter, Feeney, Sarah, and Asante-Siaw, Julius

Subjects
hemic and immune systems, chemical and pharmacologic phenomena, R1
Abstract

Summary\ud \ud CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology.

Published
2017

44. Homesweet Homegrown : How to Grow, Make, and Store Your Own Food, No Matter Where You Live

Author

Jasko, Robyn, Biggs, Jennifer, Jasko, Robyn, and Biggs, Jennifer

Subjects
Cooking (Vegetables), Canning and preserving, Self-reliant living, Sustainable living, Vegetable gardening, Fruit-culture
Abstract

A guide to sustainable living offers advice on choosing, starting, and maintaining plants; making seedling pots, composters, and a drip irrigation system; and cooking, canning, and preserving garden vegetables.

Published
2012

45. Targeted next-generation sequencing makes new molecular diagnoses and expands genotype–phenotype relationship in Ehlers–Danlos syndrome

Author

Weerakkody, Ruwan A., primary, Vandrovcova, Jana, additional, Kanonidou, Christina, additional, Mueller, Michael, additional, Gampawar, Piyush, additional, Ibrahim, Yousef, additional, Norsworthy, Penny, additional, Biggs, Jennifer, additional, Abdullah, Abdulshakur, additional, Ross, David, additional, Black, Holly A., additional, Ferguson, David, additional, Cheshire, Nicholas J., additional, Kazkaz, Hanadi, additional, Grahame, Rodney, additional, Ghali, Neeti, additional, Vandersteen, Anthony, additional, Pope, F. Michael, additional, and Aitman, Timothy J., additional

Published
2016
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46. Assessment of cone beam CT registration for prostate radiation therapy: Fiducial marker and soft tissue methods

Author

Deegan, Tim, Owen, Rebecca, Holt, Tanya, Fielding, Andrew, Biggs, Jennifer, Parfitt, Matthew, Coates, Alicia, Roberts, Lisa, Deegan, Tim, Owen, Rebecca, Holt, Tanya, Fielding, Andrew, Biggs, Jennifer, Parfitt, Matthew, Coates, Alicia, and Roberts, Lisa

Abstract

Introduction This investigation aimed to assess the consistency and accuracy of radiation therapists (RTs) performing cone beam computed tomography (CBCT) alignment to fiducial markers (FMs) (CBCTFM) and the soft tissue prostate (CBCTST). Methods Six patients receiving prostate radiation therapy underwent daily CBCTs. Manual alignment of CBCTFM and CBCTST was performed by three RTs. Inter-observer agreement was assessed using a modified Bland–Altman analysis for each alignment method. Clinically acceptable 95% limits of agreement with the mean (LoAmean) were defined as ±2.0 mm for CBCTFM and ±3.0 mm for CBCTST. Differences between CBCTST alignment and the observer-averaged CBCTFM (AvCBCTFM) alignment were analysed. Clinically acceptable 95% LoA were defined as ±3.0 mm for the comparison of CBCTST and AvCBCTFM. Results CBCTFM and CBCTST alignments were performed for 185 images. The CBCTFM 95% LoAmean were within ±2.0 mm in all planes. CBCTST 95% LoAmean were within ±3.0 mm in all planes. Comparison of CBCTST with AvCBCTFM resulted in 95% LoA of −4.9 to 2.6, −1.6 to 2.5 and −4.7 to 1.9 mm in the superior–inferior, left–right and anterior–posterior planes, respectively. Conclusions Significant differences were found between soft tissue alignment and the predicted FM position. FMs are useful in reducing inter-observer variability compared with soft tissue alignment. Consideration needs to be given to margin design when using soft tissue matching due to increased inter-observer variability. This study highlights some of the complexities of soft tissue guidance for prostate radiation therapy.

Published
2015

47. Tracking the Genomic Evolution of Esophageal Adenocarcinoma through Neoadjuvant Chemotherapy

Author

Murugaesu, Nirupa, primary, Wilson, Gareth A., additional, Birkbak, Nicolai J., additional, Watkins, Thomas B.K., additional, McGranahan, Nicholas, additional, Kumar, Sacheen, additional, Abbassi-Ghadi, Nima, additional, Salm, Max, additional, Mitter, Richard, additional, Horswell, Stuart, additional, Rowan, Andrew, additional, Phillimore, Benjamin, additional, Biggs, Jennifer, additional, Begum, Sharmin, additional, Matthews, Nik, additional, Hochhauser, Daniel, additional, Hanna, George B., additional, and Swanton, Charles, additional

Published
2015
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48. Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution

Author

Fisher, Rosalie, Horswell, Stuart, Rowan, Andrew, Salm, Maximilian P., de Bruin, Elza C., Gulati, Sakshi, McGranahan, Nicholas, Stares, Mark, Gerlinger, Marco, Varela, Ignacio, Crockford, Andrew, Favero, Francesco, Quidville, Virginie, André, Fabrice, Navas, Carolina, Grönroos, Eva, Nicol, David, Hazell, Steve, Hrouda, David, O’Brien, Tim, Matthews, Nik, Phillimore, Ben, Begum, Sharmin, Rabinowitz, Adam, Biggs, Jennifer, Bates, Paul A., McDonald, Neil Q., Stamp, Gordon, Spencer-Dene, Bradley, Hsieh, James J., Xu, Jianing, Pickering, Lisa, Gore, Martin, Larkin, James, Swanton, Charles, Fisher, Rosalie, Horswell, Stuart, Rowan, Andrew, Salm, Maximilian P., de Bruin, Elza C., Gulati, Sakshi, McGranahan, Nicholas, Stares, Mark, Gerlinger, Marco, Varela, Ignacio, Crockford, Andrew, Favero, Francesco, Quidville, Virginie, André, Fabrice, Navas, Carolina, Grönroos, Eva, Nicol, David, Hazell, Steve, Hrouda, David, O’Brien, Tim, Matthews, Nik, Phillimore, Ben, Begum, Sharmin, Rabinowitz, Adam, Biggs, Jennifer, Bates, Paul A., McDonald, Neil Q., Stamp, Gordon, Spencer-Dene, Bradley, Hsieh, James J., Xu, Jianing, Pickering, Lisa, Gore, Martin, Larkin, James, and Swanton, Charles

Abstract

Background : Genomic analysis of multi-focal renal cell carcinomas from an individual with a germline VHL mutation offers a unique opportunity to study tumor evolution. Results : We perform whole exome sequencing on four clear cell renal cell carcinomas removed from both kidneys of a patient with a germline VHL mutation. We report that tumors arising in this context are clonally independent and harbour distinct secondary events exemplified by loss of chromosome 3p, despite an identical genetic background and tissue microenvironment. We propose that divergent mutational and copy number anomalies are contingent upon the nature of 3p loss of heterozygosity occurring early in tumorigenesis. However, despite distinct 3p events, genomic, proteomic and immunohistochemical analyses reveal evidence for convergence upon the PI3K-AKT-mTOR signaling pathway. Four germline tumors in this young patient, and in a second, older patient with VHL syndrome demonstrate minimal intra-tumor heterogeneity and mutational burden, and evaluable tumors appear to follow a linear evolutionary route, compared to tumors from patients with sporadic clear cell renal cell carcinoma. Conclusions : In tumors developing from a germline VHL mutation, the evolutionary principles of contingency and convergence in tumor development are complementary. In this small set of patients with early stage VHL-associated tumors, there is reduced mutation burden and limited evidence of intra-tumor heterogeneity.

Published
2014

49. Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution

Author

Fisher, Rosalie, primary, Horswell, Stuart, additional, Rowan, Andrew, additional, Salm, Maximilian P, additional, de Bruin, Elza C, additional, Gulati, Sakshi, additional, McGranahan, Nicholas, additional, Stares, Mark, additional, Gerlinger, Marco, additional, Varela, Ignacio, additional, Crockford, Andrew, additional, Favero, Francesco, additional, Quidville, Virginie, additional, André, Fabrice, additional, Navas, Carolina, additional, Grönroos, Eva, additional, Nicol, David, additional, Hazell, Steve, additional, Hrouda, David, additional, O’Brien, Tim, additional, Matthews, Nik, additional, Phillimore, Ben, additional, Begum, Sharmin, additional, Rabinowitz, Adam, additional, Biggs, Jennifer, additional, Bates, Paul A, additional, McDonald, Neil Q, additional, Stamp, Gordon, additional, Spencer-Dene, Bradley, additional, Hsieh, James J, additional, Xu, Jianing, additional, Pickering, Lisa, additional, Gore, Martin, additional, Larkin, James, additional, and Swanton, Charles, additional

Published
2014
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50. Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing: a population-based study

Author

Norsworthy, Penny J, primary, Vandrovcova, Jana, additional, Thomas, Ellen RA, additional, Campbell, Archie, additional, Kerr, Shona M, additional, Biggs, Jennifer, additional, Game, Laurence, additional, Soutar, Anne K, additional, Smith, Blair H, additional, Dominiczak, Anna F, additional, Porteous, David J, additional, Morris, Andrew D, additional, Scotland, Generation, additional, and Aitman, Timothy J, additional

Published
2014
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