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1. Low-dose GBCA administration for brain tumour dynamic contrast enhanced MRI: a feasibility study

Author

Daniel Lewis, Ka-Loh Li, Mueez Waqar, David J. Coope, Omar N. Pathmanaban, Andrew T. King, Ibrahim Djoukhadar, Sha Zhao, Timothy F. Cootes, Alan Jackson, and Xiaoping Zhu

Subjects
Medicine, Science
Abstract

Abstract A key limitation of current dynamic contrast enhanced (DCE) MRI techniques is the requirement for full-dose gadolinium-based contrast agent (GBCA) administration. The purpose of this feasibility study was to develop and assess a new low GBCA dose protocol for deriving high-spatial resolution kinetic parameters from brain DCE-MRI. Nineteen patients with intracranial skull base tumours were prospectively imaged at 1.5 T using a single-injection, fixed-volume low GBCA dose, dual temporal resolution interleaved DCE-MRI acquisition. The accuracy of kinetic parameters (ve, Ktrans, vp) derived using this new low GBCA dose technique was evaluated through both Monte-Carlo simulations (mean percent deviation, PD, of measured from true values) and an in vivo study incorporating comparison with a conventional full-dose GBCA protocol and correlation with histopathological data. The mean PD of data from the interleaved high-temporal-high-spatial resolution approach outperformed use of high-spatial, low temporal resolution datasets alone (p

Published
2024
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2. Surrogate vascular input function measurements from the superior sagittal sinus are repeatable and provide tissue-validated kinetic parameters in brain DCE-MRI

Author

Daniel Lewis, Xiaoping Zhu, David J. Coope, Sha Zhao, Andrew T. King, Timothy Cootes, Alan Jackson, and Ka-loh Li

Subjects
Medicine, Science
Abstract

Abstract Accurate vascular input function (VIF) derivation is essential in brain dynamic contrast-enhanced (DCE) MRI. The optimum site for VIF estimation is, however, debated. This study sought to compare VIFs extracted from the internal carotid artery (ICA) and its branches with an arrival-corrected vascular output function (VOF) derived from the superior sagittal sinus (VOFSSS). DCE-MRI datasets from sixty-six patients with different brain tumours were retrospectively analysed and plasma gadolinium-based contrast agent (GBCA) concentration-time curves used to extract VOF/VIFs from the SSS, the ICA, and the middle cerebral artery. Semi-quantitative parameters across each first-pass VOF/VIF were compared and the relationship between these parameters and GBCA dose was evaluated. Through a test–retest study in 12 patients, the repeatability of each semiquantitative VOF/VIF parameter was evaluated; and through comparison with histopathological data the accuracy of kinetic parameter estimates derived using each VOF/VIF and the extended Tofts model was also assessed. VOFSSS provided a superior surrogate global input function compared to arteries, with greater contrast-to-noise (p

Published
2022
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3. A Novel Multi-Model High Spatial Resolution Method for Analysis of DCE MRI Data: Insights from Vestibular Schwannoma Responses to Antiangiogenic Therapy in Type II Neurofibromatosis

Author

Ka-Loh Li, Daniel Lewis, Xiaoping Zhu, David J. Coope, Ibrahim Djoukhadar, Andrew T. King, Timothy Cootes, and Alan Jackson

Subjects
bevacizumab, DCE-MRI, neurofibromatosis type 2, prediction, treatment response, Medicine, Pharmacy and materia medica, RS1-441
Abstract

This study aimed to develop and evaluate a new DCE-MRI processing technique that combines LEGATOS, a dual-temporal resolution DCE-MRI technique, with multi-kinetic models. This technique enables high spatial resolution interrogation of flow and permeability effects, which is currently challenging to achieve. Twelve patients with neurofibromatosis type II-related vestibular schwannoma (20 tumours) undergoing bevacizumab therapy were imaged at 1.5 T both before and at 90 days following treatment. Using the new technique, whole-brain, high spatial resolution images of the contrast transfer coefficient (Ktrans), vascular fraction (vp), extravascular extracellular fraction (ve), capillary plasma flow (Fp), and the capillary permeability-surface area product (PS) could be obtained, and their predictive value was examined. Of the five microvascular parameters derived using the new method, baseline PS exhibited the strongest correlation with the baseline tumour volume (p = 0.03). Baseline ve showed the strongest correlation with the change in tumour volume, particularly the percentage tumour volume change at 90 days after treatment (p < 0.001), and PS demonstrated a larger reduction at 90 days after treatment (p = 0.0001) when compared to Ktrans or Fp alone. Both the capillary permeability-surface area product (PS) and the extravascular extracellular fraction (ve) significantly differentiated the ‘responder’ and ‘non-responder’ tumour groups at 90 days (p < 0.05 and p < 0.001, respectively). These results highlight that this novel DCE-MRI analysis approach can be used to evaluate tumour microvascular changes during treatment and the need for future larger clinical studies investigating its role in predicting antiangiogenic therapy response.

Published
2023
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4. Visualising spatial heterogeneity in glioblastoma using imaging habitats

Author

Mueez Waqar, Petra J. Van Houdt, Eline Hessen, Ka-Loh Li, Xiaoping Zhu, Alan Jackson, Mudassar Iqbal, James O’Connor, Ibrahim Djoukhadar, Uulke A. van der Heide, David J. Coope, and Gerben R. Borst

Subjects
glioblastoma, imaging, biomarker, habitats, MRI, preoperative, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Glioblastoma is a high-grade aggressive neoplasm characterised by significant intra-tumoral spatial heterogeneity. Personalising therapy for this tumour requires non-invasive tools to visualise its heterogeneity to monitor treatment response on a regional level. To date, efforts to characterise glioblastoma’s imaging features and heterogeneity have focussed on individual imaging biomarkers, or high-throughput radiomic approaches that consider a vast number of imaging variables across the tumour as a whole. Habitat imaging is a novel approach to cancer imaging that identifies tumour regions or ‘habitats’ based on shared imaging characteristics, usually defined using multiple imaging biomarkers. Habitat imaging reflects the evolution of imaging biomarkers and offers spatially preserved assessment of tumour physiological processes such perfusion and cellularity. This allows for regional assessment of treatment response to facilitate personalised therapy. In this review, we explore different methodologies to derive imaging habitats in glioblastoma, strategies to overcome its technical challenges, contrast experiences to other cancers, and describe potential clinical applications.

Published
2022
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5. Detection of early changes in the post-radiosurgery vestibular schwannoma microenvironment using multinuclear MRI

Author

Daniel Lewis, Damien J. McHugh, Ka-loh Li, Xiaoping Zhu, Catherine Mcbain, Simon K. Lloyd, Alan Jackson, Omar N. Pathmanaban, Andrew T. King, and David J. Coope

Subjects
Medicine, Science
Abstract

Abstract Stereotactic radiosurgery (SRS) is an established, effective therapy against vestibular schwannoma (VS). The mechanisms of tumour response are, however, unknown and in this study we sought to evaluate changes in the irradiated VS tumour microenvironment through a multinuclear MRI approach. Five patients with growing sporadic VS underwent a multi-timepoint comprehensive MRI protocol, which included diffusion tensor imaging (DTI), dynamic contrast-enhanced (DCE) MRI and a spiral 23Na-MRI acquisition for total sodium concentration (TSC) quantification. Post-treatment voxelwise changes in TSC, DTI metrics and DCE-MRI derived microvascular biomarkers (Ktrans, ve and vp) were evaluated and compared against pre-treatment values. Changes in tumour TSC and microvascular parameters were observable as early as 2 weeks post-treatment, preceding changes in structural imaging. At 6 months post-treatment there were significant voxelwise increases in tumour TSC (p

Published
2021
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6. Effect of oxaliplatin plus 5-fluorouracil or capecitabine on circulating and imaging biomarkers in patients with metastatic colorectal cancer: a prospective biomarker study

Author

Reem D. Mahmood, Danielle Shaw, Tine Descamps, Cong Zhou, Robert D. Morgan, Saifee Mullamitha, Mark Saunders, Nerissa Mescallado, Alison Backen, Karen Morris, Ross A. Little, Susan Cheung, Yvonne Watson, James P. B. O’Connor, Alan Jackson, Geoff J. M. Parker, Caroline Dive, and Gordon C. Jayson

Subjects
Colorectal cancer, Angiogenesis, Biomarkers, Bevacizumab, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Patients with metastatic colorectal cancer are treated with cytotoxic chemotherapy supplemented by molecularly targeted therapies. There is a critical need to define biomarkers that can optimise the use of these therapies to maximise efficacy and avoid unnecessary toxicity. However, it is important to first define the changes in potential biomarkers following cytotoxic chemotherapy alone. This study reports the impact of standard cytotoxic chemotherapy across a range of circulating and imaging biomarkers. Methods A single-centre, prospective, biomarker-driven study. Eligible patients included those diagnosed with colorectal cancer with liver metastases that were planned to receive first line oxaliplatin plus 5-fluorouracil or capecitabine. Patients underwent paired blood sampling and magnetic resonance imaging (MRI), and biomarkers were associated with progression-free survival (PFS) and overall survival (OS). Results Twenty patients were recruited to the study. Data showed that chemotherapy significantly reduced the number of circulating tumour cells as well as the circulating concentrations of Ang1, Ang2, VEGF-A, VEGF-C and VEGF-D from pre-treatment to cycle 2 day 2. The changes in circulating concentrations were not associated with PFS or OS. On average, the MRI perfusion/permeability parameter, K trans, increased in response to cytotoxic chemotherapy from pre-treatment to cycle 2 day 2 and this increase was associated with worse OS (HR 1.099, 95%CI 1.01–1.20, p = 0.025). Conclusions In patients diagnosed with colorectal cancer with liver metastases, treatment with standard chemotherapy changes cell- and protein-based biomarkers, although these changes are not associated with survival outcomes. In contrast, the imaging biomarker, K trans, offers promise to direct molecularly targeted therapies such as anti-angiogenic agents.

Published
2021
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7. Nutritional perspectives on sickle cell disease in Africa: a systematic review

Author

Eunice Berko Nartey, Jonathan Spector, Seth Adu-Afarwuah, Catherine L. Jones, Alan Jackson, Agartha Ohemeng, Rajiv Shah, Alice Koryo-Dabrah, Amma Benneh-Akwasi Kuma, Hyacinth I. Hyacinth, and Matilda Steiner-Asiedu

Subjects
Nutritional status, Malnutrition, Sickle cell disease, Sickle cell anemia, Systematic review, Nutrition. Foods and food supply, TX341-641, Food processing and manufacture, TP368-456, Medicine (General), R5-920
Abstract

Abstract Background Sickle cell disease (SCD) is an inherited blood disorder that predominantly affects individuals in sub-Saharan Africa. However, research that elucidates links between SCD pathophysiology and nutritional status in African patients is lacking. This systematic review aimed to assess the landscape of studies in sub-Saharan Africa that focused on nutritional aspects of SCD, and highlights gaps in knowledge that could inform priority-setting for future research. Methods The study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Inclusion criteria comprised original, peer-reviewed research published between January 1995 and November 2020 involving individuals in Africa with any phenotypic variant of SCD and at least one nutritional status outcome. Nutritional status outcomes were defined as those that assessed dietary intakes, growth/anthropometry, or nutritional biomarkers. Databases used were Ovid Embase, Medline, Biosis and Web of Science. Results The search returned 526 articles, of which 76 were included in the final analyses. Most investigations (67%) were conducted in Nigeria. Studies were categorized into one of three main categories: descriptive studies of anthropometric characteristics (49%), descriptive studies of macro- or micronutrient status (41%), and interventional studies (11%). Findings consistently included growth impairment, especially among children and adolescents from sub-Saharan Africa. Studies assessing macro- and micronutrients generally had small sample sizes and were exploratory in nature. Only four randomized trials were identified, which measured the impact of lime juice, long-chain fatty acids supplementation, ready-to-use supplementary food (RUSF), and oral arginine on health outcomes. Conclusions The findings reveal a moderate number of descriptive studies, most with small sample sizes, that focused on various aspects of nutrition and SCD in African patients. There was a stark dearth of interventional studies that could be used to inform evidence-based changes in clinical practice. Findings from the investigations were generally consistent with data from other regional settings, describing a significant risk of growth faltering and malnutrition among individuals with SCD. There is an unmet need for clinical research to better understand the potential benefits of nutrition-related interventions for patients with SCD in sub-Saharan Africa to promote optimal growth and improve health outcomes.

Published
2021
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9. Plasma Tie2 is a tumor vascular response biomarker for VEGF inhibitors in metastatic colorectal cancer

Author

Gordon C. Jayson, Cong Zhou, Alison Backen, Laura Horsley, Kalena Marti-Marti, Danielle Shaw, Nerissa Mescallado, Andrew Clamp, Mark P. Saunders, Juan W. Valle, Saifee Mullamitha, Mike Braun, Jurjees Hasan, Delyth McEntee, Kathryn Simpson, Ross A. Little, Yvonne Watson, Susan Cheung, Caleb Roberts, Linda Ashcroft, Prakash Manoharan, Stefan J. Scherer, Olivia del Puerto, Alan Jackson, James P. B. O’Connor, Geoff J. M. Parker, and Caroline Dive

Subjects
Science
Abstract

Identification of response biomarkers is a key step towards the development of personalised care. Here, Jayson et al. identify plasma Tie2 as a biomarker for the response of the tumor vasculature to anti-angiogenics in patients with metastatic colorectal cancer, suggesting that monitoring Tie2 levels may help guide therapy in the clinics.

Published
2018
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10. Outcomes of children aged 6–59 months with severe acute malnutrition at the GADO Outpatient Therapeutic Center in Cameroon

Author

Judwin Alieh Ndzo and Alan Jackson

Subjects
Severe acute malnutrition, Outpatient treatment center, Treatment outcomes, Cameroon, Medicine, Biology (General), QH301-705.5, Science (General), Q1-390
Abstract

Abstract Objective We aimed to assess outcomes [rates of recovery, default, case fatality; rate of weight gain and rate of Mean Upper Arm Circumference (MUAC) gain] of children aged 6–59 months with severe acute malnutrition (SAM) at the Outpatient Therapeutic Center at Gado Refugee Camp, Cameroon, in relation to international standards. We retrospectively analysed files of 254 children with SAM aged 6–59 months admitted from April 2015 to August 2016. Results 72.8% got discharged as recovered, 0.8% died and none defaulted. 26.8% got referred to stabilization center, mostly for poor weight gain (44.1%). Mean rate of weight gain was 4.4 g/kg/day and MUAC gain 0.3 mm/cm/day; median duration of treatment 44.5 days. Amongst those with marasmus, kwashiorkor and marasmic kwashiorkor, median duration of stay was 48, 24.5 and 36.3 days (p = 0.002); recovery rates were similar 73, 71.4, 71.4% respectively (p = 0.7); Median rates of weight gain, 4.4, 6.7 and 8.1 g/kg/day (p = 0.05). 49 children had been incorrectly diagnosed and treated as SAM. International Standards were met in terms of case fatality rate and default rate but not rates of recovery and weight gain. Separate gender charts must be used to calculate weight for height z scores as combined charts cause significant errors.

Published
2018
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11. Profitability measures of dairy cows Medidas de rentabilidade de vacas leiteiras

Author

Anamaria Cândido Ribeiro, Alan Jackson McAllister, and Sandra Aidar de Queiroz

Subjects
eficiência, Holandês, produção de leite, receita vitalícia, efficiency, Holstein, lifetime income, milk yield, Animal culture, SF1-1100
Abstract

This study was aimed at defining profitability measures designed for prediction of breeding values (EBV) in dairy cows. Performance and economic data recorded in herds enrolled in the DHIA (Dairy Herd Improvement Association) program in Kentucky, USA, were used to evaluate economic functions which included the following profitability measures: lifetime net income (LNI), efficiency (EF), milk income over feed costs (IOFC), net income per day of productive life (NIPL), net income at the end of the first lactation (NI1), and milk income over feed costs at the end of the first lactation (IOFC1). The estimated averages for LNI, EF, IOFC, NIPL, NI1 and IOFC1 were respectively US$ 532.13, 1.04, US$ 3038.19, US$ -0.16, US$ -69.34 and US$ 1293.77. The heritability estimates for these traits ranged from 0.06 to 0.09. The EBV and Spearman correlation estimates were positive, ranging from moderate to high values, suggesting a direct linear relationship among the profitability measures. LNI was the best profitability measure and genetic correlation estimates between LNI and economic measures recorded in first lactation (NI1 and IOFC1) were moderate (Os objetivos neste trabalho foram definir funções econômicas para vacas leiteiras, classificar os animais por seus valores genéticos estimados (EBV) para cada uma destas medidas de rentabilidade e estimar correlações entre esses valores. As informações utilizadas foram provenientes de rebanhos participantes do programa da DHIA (Dairy Herd Improvement Association), em Kentucky, Estados Unidos. As características estudadas foram receita líquida vitalícia (LNI), eficiência (EF), receita do leite menos o custo de alimentação (IOFC), receita líquida por dia de vida produtiva (NIPL), receita líquida ao final da primeira lactação (NI1) e receita do leite menos o custo de alimentação ao final da primeira lactação (IOFC1). Os valores médios estimados foram US$ 532,13; 1,04; US$ 3038,19; US$ -0,16; US$ -69,34; e US$ 1293,77, respectivamente para LNI, EF, IOFC, NIPL, NI1 e IOFC1. As estimativas de herdabilidade variaram de 0,06 a 0,09. As correlações entre EBV e as de Spearman foram positivas, com valores moderados a altos, o que sugere relação linear direta entre as variáveis. As correlações estimadas entre EBV de LNI, função mais completa, e NI1 e IOFC1 foram moderadas (

Published
2008
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12. Update

Author

Jonathan Gornall, Alan Jackson, Wayne Roberts, The Update team, Shannon Hayes, and Seva Khambadkone

Subjects
Nutrition. Foods and food supply, TX341-641, Food processing and manufacture, TP368-456
Abstract

UK and the sugar interest Jonathan Gornall, Alan Jackson The Brazilian dietary guidelines Wayne Roberts Soda and diabetes in Mexico The Update team Feeding one another Shannon Hayes Vision for this century Seva Khambadkone

Published
2015

13. The Accuracy of ADC Measurements in Liver Is Improved by a Tailored and Computationally Efficient Local-Rigid Registration Algorithm.

Author

Hossein Ragheb, Neil A Thacker, Jean-Marie Guyader, Stefan Klein, Nandita M deSouza, and Alan Jackson

Subjects
Medicine, Science
Abstract

This study describes post-processing methodologies to reduce the effects of physiological motion in measurements of apparent diffusion coefficient (ADC) in the liver. The aims of the study are to improve the accuracy of ADC measurements in liver disease to support quantitative clinical characterisation and reduce the number of patients required for sequential studies of disease progression and therapeutic effects. Two motion correction methods are compared, one based on non-rigid registration (NRA) using freely available open source algorithms and the other a local-rigid registration (LRA) specifically designed for use with diffusion weighted magnetic resonance (DW-MR) data. Performance of these methods is evaluated using metrics computed from regional ADC histograms on abdominal image slices from healthy volunteers. While the non-rigid registration method has the advantages of being applicable on the whole volume and in a fully automatic fashion, the local-rigid registration method is faster while maintaining the integrity of the biological structures essential for analysis of tissue heterogeneity. Our findings also indicate that the averaging commonly applied to DW-MR images as part of the acquisition protocol should be avoided if possible.

Published
2015
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14. Semi-quantitative parameter analysis of DCE-MRI revisited: monte-carlo simulation, clinical comparisons, and clinical validation of measurement errors in patients with type 2 neurofibromatosis.

Author

Alan Jackson, Ka-Loh Li, and Xiaoping Zhu

Subjects
Medicine, Science
Abstract

PurposeTo compare semi-quantitative (SQ) and pharmacokinetic (PK) parameters for analysis of dynamic contrast enhanced MR data (DCE-MRI) and investigate error-propagation in SQ parameters.MethodsClinical data was collected from five patients with type 2-neurofibromatosis (NF2) receiving anti-angiogenic therapy for rapidly growing vestibular schwannoma (VS). There were 7 VS and 5 meningiomas. Patients were scanned prior to therapy and at days 3 and 90 of treatment. Data was collected using a dual injection technique to permit direct comparison of SQ and PK parameters. Monte Carlo modeling was performed to assess potential measurement errors in SQ parameters in persistent, washout, and weakly enhancing tissues. The simulation predictions for five semi-quantitative parameters were tested using the clinical DCE-MRI data.ResultsIn VS, SQ parameters and Ktrans showed close correlation and demonstrated similar therapy induced reductions. In meningioma, only the denoised Signal Enhancement Ratio (Rse1/se2(DN)) showed a significant therapy induced reduction (pConclusionPK and SQ parameters showed similar sensitivity to anti-angiogenic therapy induced changes in VS. Modeling studies confirmed the benefits of averaging baseline signal from multiple images for normalized SQ metrics and demonstrated poor noise tolerance in the widely used signal enhancement ratio, which is corrected by removal of outlier values.

Published
2014
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15. Impact of Gas Delivery Systems on Imaging Studies of Human Cerebral Blood Flow

Author

John R. Cain, Laura M. Parkes, Peter Eadsforth, Susan C. Beards, and Alan Jackson

Subjects
Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract

Purpose. To compare a semiopen breathing circuit with a non-rebreathing (Hudson mask) for MRI experiments involving gas delivery. Methods and Materials. Cerebral blood flow (CBF) was measured by quantitative phase contrast angiography of the internal carotid and basilar arteries in 18 volunteers (20–31 years). In 8 subjects, gases were delivered via a standard non-rebreathing (Hudson mask). In 10 subjects, gases were delivered using a modified “Mapleson A” semiopen anesthetic gas circuit and mouthpiece. All subjects were given 100% O2, medical air, and carbogen gas (95% O2 and 5% CO2) delivered at 15 L/min in a random order. Results. The Hudson mask group showed significant increases in CBF in response to increased FiCO2 compared to air (+9.8%). A small nonsignificant reduction in CBF (−2.4%) was seen in response to increased inspired concentrations of oxygen (FiO2). The Mapleson A group showed significantly larger changes in CBF in response to both increased inspired concentrations of carbon dioxide (FiCO2) (+32.2%, P

Published
2013
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16. Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex

Author

Tae Won Yi, Brendan Smyth, Gian Luca Di Tanna, Clare Arnott, Kathryn Cardoza, Amy Kang, Carol Pollock, Rajiv Agarwal, George Bakris, David M. Charytan, Dick de Zeeuw, Hiddo J.L. Heerspink, Bruce Neal, David C. Wheeler, Christopher P. Cannon, Hong Zhang, Bernard Zinman, Vlado Perkovic, Adeera Levin, Kenneth W. Mahaffey, Meg Jardine, Barry M. Brenner, Tom Greene, Meg J. Jardine, Gary Meininger, Nicole Li, Inna Kolesnyk, Diego Aizenberg, Roberto Pecoits-Filho, David Cherney, Gregorio Obrador, Glenn Chertow, Tara Chang, Carmel Hawley, Linong Ji, Takashi Wada, Vivekanand Jha, Soo Kun Lim, Mary Anne Lim-Abrahan, Florence Santos, Dong-Wan Chae, Shang-Jyh Hwang, Evgueniy Vazelov, Ivan Rychlík, Samy Hadjadj, Vera Krane, László Rosivall, Luca De Nicola, Alexander Dreval, Michał Nowicki, Adalbert Schiller, Larry Distiller, Jose L. Górriz, Mykola Kolesnyk, null David, C. Wheeler, Rodolfo Andres Ahuad Guerrero, Juan Pablo Albisu, Andres Alvarisqueta, Ines Bartolacci, Mario Alberto Berli, Anselmo Bordonava, Pedro Calella, Maria Cecilia Cantero, Luis Rodolfo Cartasegna, Esteban Cercos, Gabriela Cecilia Coloma, Hugo Colombo, Victor Commendatore, Jesus Cuadrado, Carlos Alberto Cuneo, Ana Maria Cusumano, Walter Guillermo Douthat, Ricardo Dario Dran, Eduardo Farias, Maria Florencia Fernandez, Hernan Finkelstein, Guillermo Fragale, Jose Osvaldo Fretes, Nestor Horacio Garcia, Anibal Gastaldi, Elizabeth Gelersztein, Jorge Archibaldo Glenny, Joaquin Pablo Gonzalez, Patricia del Carmen Gonzalez Colaso, Claudia Goycoa, Gustavo Cristian Greloni, Adrian Guinsburg, Sonia Hermida, Luis Isaias Juncos, Maria Isabel Klyver, Florencia Kraft, Fernando Krynski, Paulina Virginia Lanchiotti, Ricardo Alfonso Leon de la Fuente, Nora Marchetta, Pablo Mele, Silvia Nicolai, Pablo Antonio Novoa, Silvia Ines Orio, Fabian Otreras, Alejandra Oviedo, Pablo Raffaele, Jorge Hector Resk, Lucas Rista, Nelson Rodriguez Papini, Jorgelina Sala, Juan Carlos Santos, Lilia Beatriz Schiavi, Horacio Sessa, Tomas Smith Casabella, Maria Rosa Ulla, Maria Valdez, Augusto Vallejos, Adriana Villarino, Virginia Esther Visco, Alfredo Wassermann, Cesar Javier Zaidman, Ngai Wah Cheung, Carolyn Droste, Ian Fraser, David Johnson, Peak Mann Mah, Kathy Nicholls, David Packham, Joseph Proietto, Anthony Roberts, Simon Roger, Venessa Tsang, Roberto Abrão Raduan, Fernando Augusto Alves da Costa, Celso Amodeo, Luiz Alberto Andreotti Turatti, Rachel Bregman, Fernanda Cristina Camelo Sanches, Luis Henrique Canani, Antônio Roberto Chacra, João Lindolfo Cunha Borges, Sérgio Alberto Cunha Vêncio, Roberto Jorge da Silva Franco, Domingos d’Avila, Evandro de Souza Portes, Pedro de Souza, Luciane Mônica Deboni, Fadlo Fraige Filho, Bruno Geloneze Neto, Marcus Gomes, Suely Keiko Kohara, Elizete Keitel, Jose Francisco Kerr Saraiva, Hugo Roberto Kurtz Lisboa, Fabiana Loss de Carvalho Contieri, Rosângela Milagres, Renan Montenegro Junior, Claudia Moreira de Brito, Miguel Nasser Hissa, Ângela Regina Nazario Sabbag, Irene Noronha, Daniel Panarotto, Roberto Pecoits Filho, Márcio Antônio Pereira, Wladmir Saporito, Antonio Scafuto Scotton, Tiago Schuch, Roberto Simões de Almeida, Cássio Slompo Ramos, João Soares Felício, Fernando Thomé, Jean Carlo Tibes Hachmann, Sérgio Yamada, Cesar Yoiti Hayashida, Tarissa Beatrice Zanata Petry, Maria Teresa Zanella, Viktoria Andreeva, Angelina Angelova, Stefan Dimitrov, Veselka Genadieva, Gabriela Genova-Hristova, Kiril Hristozov, Zdravko Kamenov, Atanas Koundurdjiev, Lachezar Lozanov, Viktor Margaritov, Boyan Nonchev, Rangel Rangelov, Alexander Shinkov, Margarita Temelkova, Ekaterina Velichkova, Andrian Yakov, Naresh Aggarwal, Ronnie Aronson, Harpreet Bajaj, Guy Chouinard, James Conway, Serge Cournoyer, Gerald DaRoza, Sacha De Serres, François Dubé, Ronald Goldenberg, Anil Gupta, Milan Gupta, Sam Henein, Hasnain Khandwala, Lawrence Leiter, François Madore, Alan McMahon, Norman Muirhead, Vincent Pichette, Remi Rabasa-Lhoret, Andrew Steele, Navdeep Tangri, Ali Torshizi, Vincent Woo, Nadia Zalunardo, María Alicia Fernández Montenegro, Juan Gonzalo Godoy Jorquera, Marcelo Medina Fariña, Victor Saavedra Gajardo, Margarita Vejar, Nan Chen, Qinkai Chen, Shenglian Gan, Yaozhong Kong, Detian Li, Wenge Li, Xuemei Li, Hongli Lin, Jian Liu, Weiping Lu, Hong Mao, Yan Ren, Weihong Song, Jiao Sun, Lin Sun, Ping Tu, Guixia Wang, Jinkui Yang, Aiping Yin, Xueqing Yu, Minghui Zhao, Hongguang Zheng, Jose Luis Accini Mendoza, Edgar Arcos, Jorge Avendano, Jorge Ernesto Andres Diaz Ruiz, Luis Hernando Garcia Ortiz, Alexander Gonzalez, Eric Hernandez Triana, Juan Diego Higuera, Natalia Malaver, Dora Inés Molina de Salazar, Ricardo Rosero, Monica Alexandra Terront Lozano, Luis Valderrama Cometa, Alex Valenzuela, Ruben Dario Vargas Alonso, Ivan Villegas, Hernan Yupanqui, Dagmar Bartaskova, Petr Barton, Jana Belobradkova, Lenka Dohnalova, Tomas Drasnar, Richard Ferkl, Katarina Halciakova, Vera Klokocnikova, Richard Kovar, Jiri Lastuvka, Martin Lukac, Satu Pesickova, Karel Peterka, Jiri Pumprla, Ivan Rychlik, Frantisek Saudek, Vladimir Tesar, Martin Valis, Pavel Weiner, Stanislav Zemek, Eric Alamartine, Sophie Borot, Bertrand Cariou, Bertrand Dussol, Jean-Pierre Fauvel, Pierre Gourdy, Alexandre Klein, Yannick Le Meur, Alfred Penfornis, Ronan Roussel, Pierre-Jean Saulnier, Eric Thervet, Philippe Zaoui, Volker Burst, Markus Faghih, Grit Faulmann, Hermann Haller, Reinhold Jerwan-Keim, Stephan Maxeiner, Björn Paschen, Georg Plassmann, Ludger Rose, Ronaldo Arturo Gonzalez Orellana, Franklin Paul Haase, Juan Pablo Moreira Diaz, Luis Alberto Ramirez Roca, Jose Antonio Sánchez Arenales, José Vicente Sanchez Polo, Erick Turcios Juarez, Gyongyi Csecsei, Botond Csiky, Peter Danos, Laszlo Deak, Mihaly Dudas, Eleonora Harcsa, Katalin Keltai, Sandor Keresztesi, Krisztian Kiss, Laszlo Konyves, Lajos Major, Margit Mileder, Marta Molnar, Janos Mucsi, Tamas Oroszlan, Ivan Ory, Gyorgy Paragh, Eva Peterfai, Gizella Petro, Katalin Revesz, Robert Takacs, Sandor Vangel, Szilard Vasas, Marianna Zsom, Oomman Abraham, Raju Sree Bhushan, Dewan Deepak, Fernando M. Edwin, Natarajan Gopalakrishnan, Noble Gracious, Alva Hansraj, Dinesh Jain, C.B. Keshavamurthy, Dinesh Khullar, Sahay Manisha, Jayameena Peringat, Narayan Prasad, Rao K. Satyanarayana, Reddy Sreedhar, Melemadathil Sreelatha, Bhimavarapu Sudhakar, Ramesh Chandra Vyasam, Riccardo Bonadonna, Pietro Castellino, Antonio Ceriello, Luca Chiovato, Salvatore De Cosmo, Giuseppe Derosa, Alberto Di Carlo, Graziano Di Cianni, Giovanni Frascà, Giorgio Fuiano, Giovanni Gambaro, Giacomo Garibotto, Carlo Giorda, Fabio Malberti, Marcora Mandreoli, Edoardo Mannucci, Emanuela Orsi, Piermarco Piatti, Domenico Santoro, Ferdinando Carlo Sasso, Gaetano Serviddio, Andrea Stella, Roberto Trevisan, Anna Maria Veronelli, Luca Zanoli, Hitoshi Akiyama, Hiromi Aoki, Akimichi Asano, Tadashi Iitsuka, Shizuo Kajiyama, Susumu Kashine, Toshio Kawada, Takamoto Kodera, Hiroshi Kono, Kazunori Koyama, Yasuro Kumeda, Shozo Miyauchi, Kazuyuki Mizuyama, Tetsuji Niiya, Hiroko Oishi, Satoshi Ota, Terue Sakakibara, Masahiko Takai, Osamu Tomonaga, Mitsuru Tsujimoto, Masakiyo Wakasugi, Yasushi Wakida, Takayuki Watanabe, Masayo Yamada, Kazuhiro Yanagida, Toshihiko Yanase, Wataru Yumita, Egle Gaupsiene, Dalia Kozloviene, Antanas Navickas, Egle Urbanaviciene, Rohana Abdul Ghani, Khalid Abdul Kadir, Norsiah Ali, Mohd Daud Che Yusof, Chye Lee Gan, Mastura Ismail, Wei Yen Kong, Swee Win Lam, Li Yuan Lee, Chek Loong Loh, Anita Bhajan Manocha, Kee Sing Ng, Nik Nur Fatnoon Nik Ahmad, Vanassa Ratnasingam, Saiful Shahrizal Bin Shudim, Paranthaman Vengadasalam, Luis David Abraira Munoz, Melchor Alpizar Salazar, Juan Baas Cruz, Mario Burgos Soto, Jose Chevaile Ramos, Alfredo Chew Wong, Jose Ricardo Correa Rotter, Tonatiu Diaz Escalante, Favio Edmundo Enriquez Sosa, Fernando Flores Lozano, Luis Fernando Flota Cervera, Paul Frenk Baron, Cecilia Garcia Ballesteros, Jose David Gomez Rangel, Luis Enrique Herrera Jimenez, Sergio Saul Irizar Santana, Fernando Jimenez Flores, Hugo Laviada Molina, Rosa Isela Luna Ceballos, Belia Martin del Campo Blanco, Guadalupe Morales Franco, Oscar Tarsicio Moreno Loza, Cynthia Mustieles Rocha, Gregorio Obrador Vera, Ricardo Orozco Castellanos, Juan Peralta Calcaneo, Miguel Angel Reyes Rosano, Hiromi Rodriguez Pattzi, Juan Rosas Guzman, Isabel Erika Rucker Joerg, Sandra Berenice Saavedra Sanchez, Jose Hector Sanchez Mijangos, Pablo Serrano Sanson, Juan Alfredo Tamayo y Orozco, Eloisa Tellez Chavez, Alejandro Valdes Cepeda, Luis Venegas Carrillo, Juan Villagordoa Mesa, Rolando Zamarripa Escobedo, John Baker, Paul Noonan, Russell Scott, Robert Walker, Edward Watson, Michael Williams, Simon Young, Zaynab Abejuela, Jeimeen Agra, Grace Aquitania, Clodoaido Caringal, Rhea Severina Comia, Lalaine Delos Santos, Olivert Gomez, Cecilia Jimeno, Gerry Tan, Marsha Tolentino, Christy Yao, Yvette Ethel Yap, Ma. Dovie Lallaine Ygpuara, Renata Bijata-Bronisz, Lucyna Hotlos, Andrzej Januszewicz, Barbara Kaczmarek, Anna Kaminska, Lech Lazuka, Andrzej Madej, Stanislaw Mazur, Dorota Mlodawska-Choluj, Michal Nowicki, Grazyna Orlowska-Kowalik, Grazyna Popenda, Barbara Rewerska, Dariusz Sowinski, Liliana Monica Angelescu, Veronica Anghel, Rodica-Ioana Avram, Mihaela-Magdalena Busegeanu, Adriana Cif, Dana Cosma, Carmen Crisan, Luiza Despina Demian, Ioana Emilia Ferariu, Ildiko Halmagyi, Nicolae Hancu, Mircea Munteanu, Doru Negru, Adriana Gabriela Onaca, Ligia Petrica, Amorin Remus Popa, Aurelian-Emil Ranetti, Cristian Serafinceanu, Cristina Toarba, Alina Agafyina, Olga Barbarash, Olga Barysheva, Daniil Chizhov, Vladimir Dobronravov, Irina Glinkina, Elena Grineva, Vladimir Khirmanov, Elena Kolmakova, Tatiana Koroleva, Liudmila Kvitkova, Viacheslav Marasaev, Ashot Mkrtumyan, Tatiana Morugova, Galina Nagibovich, Oleg Nagibovich, Sergei Nedogoda, Irina Osipova, Tatiana Raskina, Yulia Samoylova, Olga Sazonova, Minara Shamkhalova, Elena Shutemova, Yuriy Shwartz, Oleg Uriasyev, Sergey Vorobyev, Anna Zateyshchikova, Dmitry Zateyshshikov, Tatyana Zykova, Slobodan Antic, Miodrag Djordjevic, Aleksandra Kendereski, Katarina Lalic, Nebojsa Lalic, Vesna Popovic-Radinovic, Jana Babikova, Olga Benusova, Ingrid Buganova, Jan Culak, Andrej Dzupina, Jana Dzuponova, Peter Fulop, Adriana Ilavska, Emil Martinka, Zuzana Ochodnicka, Daniel Pella, Iveta Smatanova, Fayzal Ahmed, Aysha Badat, Johannes Breedt, Lawrence Distiller, Vimladhevi Govender, Ravendran Govender, Mukesh Joshi, Jaco Jurgens, Gulam Latiff, Landman Lombard, Mohamed Mookadam, Nomangesi Ngcakani, Hendrik Nortje, Helena Oosthuizen, Larisha Pillay-Ramaya, Hans Prozesky, Jeevren Reddy, Paul Rheeder, Mary Seeber, Young Min Cho, In-Kyung Jeong, Sin Gon Kim, Yeong Hoon Kim, Hyuk-Sang Kwon, Min Jeong Kwon, Byung-Wan Lee, JungEun Lee, Moon-Kyu Lee, Moon-Suk Nam, Kook-Hwan Oh, Cheol- Young Park, Sun-Hee Park, Kun Ho Yoon, Pere Alvarez Garcia, Luis Asmarats Mercadal, Clara Barrios, Fernando Cereto Castro, Secundino Cigarran Guldris, Marta Dominguez Lopez, Jesus Egido de los Rios, Gema Fernandez Fresnedo, Antonio Galan Serrano, Isabel Garcia, Francisco Javier Gonzalez Martinez, Jose Esteban Jodar Gimeno, Manuel Lopez Mendoza, Tamara Malek Marin, Cristobal Morales Portillo, Maria Antonia Munar Vila, Manuel Muñoz Torres, Javier Nieto Iglesias, Jonay Pantoja Perez, Merce Perez Vera, Jose M. Portoles Perez, María Angustias Quesada Simón, Rafael Simo Canonge, Alfonso Soto Gonzalez, Manel Terns Riera, Francisco Jose Tinahones Madueno, Mercedes Velo Plaza, Chwen-Tzuei Chang, Lee-Ming Chuang, Te-Lin Hsia, Chang-Hsun Hsieh, Chih-Ching Lin, Yung- Chuan Lu, Wayne H-H Sheu, Olga Barna, Svitlana D. Bilyk, Volodymyr Botsyurko, Iryna Dudar, Ivan Fushtey, Olga Godlevska, Oleksandr Golovchenko, Olga Gyrina, Anatoliy Kazmirchuk, Iuliia Komisarenko, Oleksii Korzh, Nonna Kravchun, Oleg Legun, Borys Mankovskyy, Liliya Martynyuk, Yuriy Mostovoy, Nataliia Pashkovska, Larysa Pererva, Tetyana Pertseva, Oleksandr Samoylov, Ivan Smirnov, Yevgeniya Svyshchenko, Halyna Tomashkevych, Ivan Topchii, Nadiya Tryshchuk, Vira Tseluyko, Vadym Vizir, Maryna Vlasenko, Tetiana Zlova, Liliia Zub, Salah Abusnana, Mohamed Railey, Kamal Abouglila, Paul Ainsworth, Zishan Ali, Vijayaraman Arutchelvam, Maria Barnard, Srikanth Bellary, Emyr Davies, Mark Davies, Simon Davies, Alison Dawson, Mohsen El Kossi, Patrick English, Donald Fraser, Luigi Gnudi, Anthony Gunstone, Timothy Hall, Wasim Hanif, Alan Jackson, Andrew Johnson, Franklin Joseph, Singhan Krishnan, Mick Kumwenda, Iain MacDougall, Paul Nixon, Joseph O'Hare, Sam Philip, Shenaz Ramtoola, Manish Saxena, Davesh Sennik, Godwin Simon, Baldev Singh, Jeffrey Stephens, Anna Strzelecka, Rehan Symonds, Wayne Turner, Mona Wahba, John Wakeling, David Wheeler, Peter Winocour, Joseph Abdallah, Raied Abdullah, Matthew Abramowitz, Idalia Acosta, Joseph Aiello, Laura Akright, Ayim Akyea-Djamson, Rajendran Alappan, Radica Alicic, Amer Al-Karadsheh, Dale Crawford Allison, Carlos Arauz-Pacheco, Shahabul Arfeen, Ahmed Arif, Moogali Arvind, Naveen Atray, Ahmed Awad, Peggy Barnhill, Elizabeth Barranco, Carlos Barrera, Matthew Beacom, Venkata Behara, Diogo Belo, Rhonda Bentley-Lewis, Ramon Berenguer, Lidia Bermudez, Marializa Bernardo, Mihaela Biscoveanu, Cynthia Bowman-Stroud, Donald Brandon, Osvaldo Brusco, Robert Busch, Yamil Canaan, Alicia Chilito, Tom Christensen, Cynthia Christiano, Elena Christofides, Caroucel Chuateco, Kenneth Cohen, Robert Cohen, Debbie Cohen-Stein, Charles Cook, Daniel Coyne, Nizar Daboul, Riad Darwish, Adarsh Daswani, Kenneth Deck, Cyrus Desouza, Devasmita Dev, Monika Dhillon, Sohan Dua, Frank Eder, Ana Maria Elosegui, Mohamed El-Shahawy, John Ervin, Alberto Esquenazi, John Evans, Steven Fishbane, Juan Frias, Eugenia Galindo-Ramos, Claude Galphin, Adline Ghazi, Enrique Gonzalez, David Gorson, Anupama Gowda, Barbara Greco, Stephen Grubb, Rakesh Gulati, Jamal Hammoud, Stuart Handelsman, Israel Hartman, Kenneth Hershon, Daniel Hiser, George Hon, Radu Jacob, Maria Jaime, Aamir Jamal, Charles Kaupke, Gerald Keightley, Elizabeth Kern, Rakhi Khanna, Zeid Khitan, Sun Kim, Nelson Kopyt, Csaba Kovesdy, Gopal Krishna, Jeffrey (Jay) Kropp, Amrendra Kumar, Jayant Kumar, Neil Kumar, Jorge Kusnir, Wendy Lane, Mary Lawrence, Lawrence Lehrner, John Lentz, Dennis Levinson, Derek Lewis, Kenneth Liss, Andreas Maddux, Hiralal Maheshwari, Sreedhar Mandayam, Isam Marar, Bhasker Mehta, John Middleton, Jorge Mordujovich, Ramon Moreda, Moustafa Moustafa, Samuel Mujica Trenche, Mohanram Narayanan, Javier Narvarte, Tareq Nassar, George Newman, Brian Nichol, Philip Nicol, Josier Nisnisan, A. Kaldun Nossuli, Chamberlain Obialo, Sarah Olelewe, Michael Oliver, Andrew O'Shaughnessy, John Padron, Rohit Pankhaniya, Reginald Parker, Devesh Patel, Gnyandev Patel, Nina Patel, Humberto Pavon, Armando Perez, Carlos Perez, Alan Perlman, Karlton Pettis, Walter Pharr, Andrea Phillips, Raman Purighalla, Luis Quesada-Suarez, Rajiv Ranjan, Sanjeev Rastogi, Jakkidi Reddy, Marc Rendell, Lisa Rich, Michael Robinson, Hector Rodriguez, Sylvia Rosas, Fadi Saba, Rallabhandi Sankaram, Ravi Sarin, Robert Schreiman, David Scott, Mohamed Sekkarie, John Sensenbrenner, Muhammad Shakeel, Michael Shanik, Sylvia Shaw, Stephen Smith, Richard Solomon, Amy Sprague, Leslie Spry, Pusadee Suchinda, Senan Sultan, Prasanth Surampudi, Sherry Sussman, Anjanette Tan, Antonio Terrelonge, Michael Thompson, Fernando Trespalacios, Bruce Trippe, Pilar Trueba, Marcel Twahirwa, John Updegrove, Peter Van Buren, Mark Vannorsdall, Freemu Varghese, Pedro Velasquez-Mieyer, Sailaja Ventrapragada, Goga Vukotic, Khurram Wadud, Mark Warren, Henry Watson, Ronald Watts, Daniel Weiner, James Welker, Jean Welsh, Shelley Williams, and Michelle Zaniewski-Singh

Subjects
age, diabetes, Nephrology, kidney outcomes, sex, Diabetic kidney disease, canagliflozin, cardiovascular outcomes, chronic kidney disease, sodium/glucose cotransporter 2 inhibitors
Abstract

Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a randomized controlled trial.Setting & Participants: Participants in the CREDENCE trial.Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (Results: The mean age of the cohort was 63.0 ± 9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.

Published
2023

19. Supplementary Data from Quantifying Antivascular Effects of Monoclonal Antibodies to Vascular Endothelial Growth Factor: Insights from Imaging

Author

Gordon C. Jayson, Nicholas van Bruggen, Napoleone Ferrara, Olivia del Puerto, Paula Thornton, Jurjees Hasan, Karen Davies, Giovanni A. Buonaccorsi, Sarajane Ross, Tim C. Cao, Xiumin Wu, Glenn J. Pacheco, Mary Ann T. Go, Hani Bou Reslan, Sue Cheung, Lynn Hope, Caleb Roberts, Yvonne Watson, Claire L. Mitchell, Michel Friesenhahn, Franklin V. Peale, Chris J. Rose, Geoff J.M. Parker, Alan Jackson, Calvin C.K. Ho, Jed Ross, Andrew R. Clamp, Richard A.D. Carano, and James P.B. O'Connor

Abstract

Supplementary Data from Quantifying Antivascular Effects of Monoclonal Antibodies to Vascular Endothelial Growth Factor: Insights from Imaging

Published
2023

20. Supplementary Video from Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non–small Cell Lung Cancer

Author

James P.B. O'Connor, Kaye J. Williams, Corinne Faivre-Finn, Geoff J.M. Parker, Alan Jackson, Robert G. Bristow, Marie-Claude Asselin, Julian C. Matthews, Caron Behan, Garry Ashton, Hitesh Mistry, Victoria Tessyman, Yvonne Watson, Susan Cheung, Isabel Peset, Muhammad Babur, Adam K. Featherstone, Ayşe Latif, Ross A. Little, and Ahmed Salem

Abstract

Supplementary Video

Published
2023

22. Additional Tables and Figures from A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multipeptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma

Author

James W.A. Ritchie, Sarah E. Halford, Harpreet Singh-Jasuja, Oliver Schoor, Karen Hill, Jane Peters, Lesley McGuigan, Norbert Hilf, Sarah Kutscher, Juha Lindner, Willie Stewart, Alan Jackson, Sarah Jefferies, Catherine McBain, Christopher J. Twelves, Omar Al-Salihi, Allan James, Paul J. Mulholland, Sharon Peoples, and Roy Rampling

Abstract

Supplementary Table S1. TUMAPs contained in IMA950 and associated source antigens. Supplementary Table S2. Statistical analysis underlying the recruitment of 20 immune evaluable patients per cohort. Supplementary Table S3. Reasons for HLA-A*02 positive patients not entering the clinical trial. Supplementary Figure S1. Study schedule. Supplementary Figure S2. Exemplary gating strategy used for the primary multimer assay. Supplementary Figure S3. Exemplary immune responses in patients as determined by multimer assay after in vitro sensitization. Supplementary Figure S4. Apparent diffusion coefficient (ADC) in Cohort 1 at each of the four scan points.

Published
2023

24. Supplementary Material from Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non–small Cell Lung Cancer

Author

James P.B. O'Connor, Kaye J. Williams, Corinne Faivre-Finn, Geoff J.M. Parker, Alan Jackson, Robert G. Bristow, Marie-Claude Asselin, Julian C. Matthews, Caron Behan, Garry Ashton, Hitesh Mistry, Victoria Tessyman, Yvonne Watson, Susan Cheung, Isabel Peset, Muhammad Babur, Adam K. Featherstone, Ayşe Latif, Ross A. Little, and Ahmed Salem

Abstract

Supplementary Material

Published
2023

25. Supplementary Figure 5 from Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non–small Cell Lung Cancer

Author

James P.B. O'Connor, Kaye J. Williams, Corinne Faivre-Finn, Geoff J.M. Parker, Alan Jackson, Robert G. Bristow, Marie-Claude Asselin, Julian C. Matthews, Caron Behan, Garry Ashton, Hitesh Mistry, Victoria Tessyman, Yvonne Watson, Susan Cheung, Isabel Peset, Muhammad Babur, Adam K. Featherstone, Ayşe Latif, Ross A. Little, and Ahmed Salem

Abstract

Supplementary Figure 5

Published
2023

26. Supplementary Figure 2 from Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non–small Cell Lung Cancer

Author

James P.B. O'Connor, Kaye J. Williams, Corinne Faivre-Finn, Geoff J.M. Parker, Alan Jackson, Robert G. Bristow, Marie-Claude Asselin, Julian C. Matthews, Caron Behan, Garry Ashton, Hitesh Mistry, Victoria Tessyman, Yvonne Watson, Susan Cheung, Isabel Peset, Muhammad Babur, Adam K. Featherstone, Ayşe Latif, Ross A. Little, and Ahmed Salem

Abstract

Supplementary Figure 2

Published
2023

27. Supplementary Figure 6 from Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non–small Cell Lung Cancer

Author

James P.B. O'Connor, Kaye J. Williams, Corinne Faivre-Finn, Geoff J.M. Parker, Alan Jackson, Robert G. Bristow, Marie-Claude Asselin, Julian C. Matthews, Caron Behan, Garry Ashton, Hitesh Mistry, Victoria Tessyman, Yvonne Watson, Susan Cheung, Isabel Peset, Muhammad Babur, Adam K. Featherstone, Ayşe Latif, Ross A. Little, and Ahmed Salem

Abstract

Supplementary Figure 6

Published
2023

28. Supplementary Figure 8 from Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non–small Cell Lung Cancer

Author

James P.B. O'Connor, Kaye J. Williams, Corinne Faivre-Finn, Geoff J.M. Parker, Alan Jackson, Robert G. Bristow, Marie-Claude Asselin, Julian C. Matthews, Caron Behan, Garry Ashton, Hitesh Mistry, Victoria Tessyman, Yvonne Watson, Susan Cheung, Isabel Peset, Muhammad Babur, Adam K. Featherstone, Ayşe Latif, Ross A. Little, and Ahmed Salem

Abstract

Supplementary Figure 8

Published
2023

29. CCR Translation for the Article from Quantifying Antivascular Effects of Monoclonal Antibodies to Vascular Endothelial Growth Factor: Insights from Imaging

Author

Gordon C. Jayson, Nicholas van Bruggen, Napoleone Ferrara, Olivia del Puerto, Paula Thornton, Jurjees Hasan, Karen Davies, Giovanni A. Buonaccorsi, Sarajane Ross, Tim C. Cao, Xiumin Wu, Glenn J. Pacheco, Mary Ann T. Go, Hani Bou Reslan, Sue Cheung, Lynn Hope, Caleb Roberts, Yvonne Watson, Claire L. Mitchell, Michel Friesenhahn, Franklin V. Peale, Chris J. Rose, Geoff J.M. Parker, Alan Jackson, Calvin C.K. Ho, Jed Ross, Andrew R. Clamp, Richard A.D. Carano, and James P.B. O'Connor

Abstract

CCR Translation for the Article from Quantifying Antivascular Effects of Monoclonal Antibodies to Vascular Endothelial Growth Factor: Insights from Imaging

Published
2023

30. Data from Quantifying Antivascular Effects of Monoclonal Antibodies to Vascular Endothelial Growth Factor: Insights from Imaging

Author

Gordon C. Jayson, Nicholas van Bruggen, Napoleone Ferrara, Olivia del Puerto, Paula Thornton, Jurjees Hasan, Karen Davies, Giovanni A. Buonaccorsi, Sarajane Ross, Tim C. Cao, Xiumin Wu, Glenn J. Pacheco, Mary Ann T. Go, Hani Bou Reslan, Sue Cheung, Lynn Hope, Caleb Roberts, Yvonne Watson, Claire L. Mitchell, Michel Friesenhahn, Franklin V. Peale, Chris J. Rose, Geoff J.M. Parker, Alan Jackson, Calvin C.K. Ho, Jed Ross, Andrew R. Clamp, Richard A.D. Carano, and James P.B. O'Connor

Abstract

Purpose: Little is known concerning the onset, duration, and magnitude of direct therapeutic effects of anti–vascular endothelial growth factor (VEGF) therapies. Such knowledge would help guide the rational development of targeted therapeutics from bench to bedside and optimize use of imaging technologies that quantify tumor function in early-phase clinical trials.Experimental Design: Preclinical studies were done using ex vivo microcomputed tomography and in vivo ultrasound imaging to characterize tumor vasculature in a human HM-7 colorectal xenograft model treated with the anti-VEGF antibody G6-31. Clinical evaluation was by quantitative magnetic resonance imaging in 10 patients with metastatic colorectal cancer treated with bevacizumab.Results: Microcomputed tomography experiments showed reduction in perfused vessels within 24 to 48 h of G6-31 drug administration (P ≤ 0.005). Ultrasound imaging confirmed reduced tumor blood volume within the same time frame (P = 0.048). Consistent with the preclinical results, reductions in enhancing fraction and fractional plasma volume were detected in patient colorectal cancer metastases within 48 h after a single dose of bevacizumab that persisted throughout one cycle of therapy. These effects were followed by resolution of edema (P = 0.0023) and tumor shrinkage in 9 of 26 tumors at day 12.Conclusion: These data suggest that VEGF-specific inhibition induces rapid structural and functional effects with downstream significant antitumor activity within one cycle of therapy. This finding has important implications for the design of early-phase clinical trials that incorporate physiologic imaging. The study shows how animal data help interpret clinical imaging data, an important step toward the validation of image biomarkers of tumor structure and function. (Clin Cancer Res 2009;15(21):6674–82)

Published
2023

31. Data from Imaging Intratumor Heterogeneity: Role in Therapy Response, Resistance, and Clinical Outcome

Author

Alan Jackson, Geoff J.M. Parker, Richard A.D. Carano, John C. Waterton, Chris J. Rose, and James P.B. O'Connor

Abstract

Tumors exhibit genomic and phenotypic heterogeneity, which has prognostic significance and may influence response to therapy. Imaging can quantify the spatial variation in architecture and function of individual tumors through quantifying basic biophysical parameters such as CT density or MRI signal relaxation rate; through measurements of blood flow, hypoxia, metabolism, cell death, and other phenotypic features; and through mapping the spatial distribution of biochemical pathways and cell signaling networks using PET, MRI, and other emerging molecular imaging techniques. These methods can establish whether one tumor is more or less heterogeneous than another and can identify subregions with differing biology. In this article, we review the image analysis methods currently used to quantify spatial heterogeneity within tumors. We discuss how analysis of intratumor heterogeneity can provide benefit over more simple biomarkers such as tumor size and average function. We consider how imaging methods can be integrated with genomic and pathology data, instead of being developed in isolation. Finally, we identify the challenges that must be overcome before measurements of intratumoral heterogeneity can be used routinely to guide patient care. Clin Cancer Res; 21(2); 249–57. ©2014 AACR.

Published
2023

32. Supplementary Figure 4 from Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non–small Cell Lung Cancer

Author

James P.B. O'Connor, Kaye J. Williams, Corinne Faivre-Finn, Geoff J.M. Parker, Alan Jackson, Robert G. Bristow, Marie-Claude Asselin, Julian C. Matthews, Caron Behan, Garry Ashton, Hitesh Mistry, Victoria Tessyman, Yvonne Watson, Susan Cheung, Isabel Peset, Muhammad Babur, Adam K. Featherstone, Ayşe Latif, Ross A. Little, and Ahmed Salem

Abstract

Supplementary Figure 4

Published
2023

33. Supplementary Figure 9 from Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non–small Cell Lung Cancer

Author

James P.B. O'Connor, Kaye J. Williams, Corinne Faivre-Finn, Geoff J.M. Parker, Alan Jackson, Robert G. Bristow, Marie-Claude Asselin, Julian C. Matthews, Caron Behan, Garry Ashton, Hitesh Mistry, Victoria Tessyman, Yvonne Watson, Susan Cheung, Isabel Peset, Muhammad Babur, Adam K. Featherstone, Ayşe Latif, Ross A. Little, and Ahmed Salem

Abstract

Supplementary Figure 9

Published
2023

34. Data from A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multipeptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma

Author

James W.A. Ritchie, Sarah E. Halford, Harpreet Singh-Jasuja, Oliver Schoor, Karen Hill, Jane Peters, Lesley McGuigan, Norbert Hilf, Sarah Kutscher, Juha Lindner, Willie Stewart, Alan Jackson, Sarah Jefferies, Catherine McBain, Christopher J. Twelves, Omar Al-Salihi, Allan James, Paul J. Mulholland, Sharon Peoples, and Roy Rampling

Abstract

Purpose: To perform a two-cohort, phase I safety and immunogenicity study of IMA950 in addition to standard chemoradiotherapy and adjuvant temozolomide in patients with newly diagnosed glioblastoma. IMA950 is a novel glioblastoma-specific therapeutic vaccine containing 11 tumor-associated peptides (TUMAP), identified on human leukocyte antigen (HLA) surface receptors in primary human glioblastoma tissue.Experimental Design: Patients were HLA-A*02–positive and had undergone tumor resection. Vaccination comprised 11 intradermal injections with IMA950 plus granulocyte macrophage colony-stimulating factor (GM-CSF) over a 24-week period, beginning 7 to 14 days prior to initiation of chemoradiotherapy (Cohort 1) or 7 days after chemoradiotherapy (Cohort 2). Safety was assessed according to NCI CTCAE Version 4.0 and TUMAP-specific T-cell immune responses determined. Secondary observations included progression-free survival (PFS), pretreatment regulatory T cell (Treg) levels, and the effect of steroids on T-cell responses.Results: Forty-five patients were recruited. Related adverse events included minor injection site reactions, rash, pruritus, fatigue, neutropenia and single cases of allergic reaction, anemia and anaphylaxis. Two patients experienced grade 3 dose-limiting toxicity of fatigue and anaphylaxis. Of 40 evaluable patients, 36 were TUMAP responders and 20 were multi-TUMAP responders, with no important differences between cohorts. No effect of pretreatment Treg levels on IMA950 immunogenicity was observed, and steroids did not affect TUMAP responses. PFS rates were 74% at 6 months and 31% at 9 months.Conclusions: IMA950 plus GM-CSF was well-tolerated with the primary immunogenicity endpoint of observing multi-TUMAP responses in at least 30% of patients exceeded. Further development of IMA950 is encouraged. Clin Cancer Res; 22(19); 4776–85. ©2016 AACR.See related commentary by Lowenstein and Castro, p. 4760

Published
2023

35. Supplementary Figure 10 from Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non–small Cell Lung Cancer

Author

James P.B. O'Connor, Kaye J. Williams, Corinne Faivre-Finn, Geoff J.M. Parker, Alan Jackson, Robert G. Bristow, Marie-Claude Asselin, Julian C. Matthews, Caron Behan, Garry Ashton, Hitesh Mistry, Victoria Tessyman, Yvonne Watson, Susan Cheung, Isabel Peset, Muhammad Babur, Adam K. Featherstone, Ayşe Latif, Ross A. Little, and Ahmed Salem

Abstract

Supplementary Figure 10

Published
2023

36. Supplementary Tables from Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non–small Cell Lung Cancer

Author

James P.B. O'Connor, Kaye J. Williams, Corinne Faivre-Finn, Geoff J.M. Parker, Alan Jackson, Robert G. Bristow, Marie-Claude Asselin, Julian C. Matthews, Caron Behan, Garry Ashton, Hitesh Mistry, Victoria Tessyman, Yvonne Watson, Susan Cheung, Isabel Peset, Muhammad Babur, Adam K. Featherstone, Ayşe Latif, Ross A. Little, and Ahmed Salem

Abstract

Supplementary Tables

Published
2023

37. Supplementary Figure 7 from Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non–small Cell Lung Cancer

Author

James P.B. O'Connor, Kaye J. Williams, Corinne Faivre-Finn, Geoff J.M. Parker, Alan Jackson, Robert G. Bristow, Marie-Claude Asselin, Julian C. Matthews, Caron Behan, Garry Ashton, Hitesh Mistry, Victoria Tessyman, Yvonne Watson, Susan Cheung, Isabel Peset, Muhammad Babur, Adam K. Featherstone, Ayşe Latif, Ross A. Little, and Ahmed Salem

Abstract

Supplementary Figure 7

Published
2023

38. Supplementary Figure 3 from Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non–small Cell Lung Cancer

Author

James P.B. O'Connor, Kaye J. Williams, Corinne Faivre-Finn, Geoff J.M. Parker, Alan Jackson, Robert G. Bristow, Marie-Claude Asselin, Julian C. Matthews, Caron Behan, Garry Ashton, Hitesh Mistry, Victoria Tessyman, Yvonne Watson, Susan Cheung, Isabel Peset, Muhammad Babur, Adam K. Featherstone, Ayşe Latif, Ross A. Little, and Ahmed Salem

Abstract

Supplementary Figure 3

Published
2023

39. Data from Oxygen-Enhanced MRI Accurately Identifies, Quantifies, and Maps Tumor Hypoxia in Preclinical Cancer Models

Author

Simon P. Robinson, John C. Waterton, Andrew R. Reynolds, Geoff J.M. Parker, Alan Jackson, Ross A. Little, Kaye J. Williams, Katherine G. Finegan, Muhammad Babur, Yann Jamin, Jessica K.R. Boult, and James P.B. O'Connor

Abstract

There is a clinical need for noninvasive biomarkers of tumor hypoxia for prognostic and predictive studies, radiotherapy planning, and therapy monitoring. Oxygen-enhanced MRI (OE-MRI) is an emerging imaging technique for quantifying the spatial distribution and extent of tumor oxygen delivery in vivo. In OE-MRI, the longitudinal relaxation rate of protons (ΔR1) changes in proportion to the concentration of molecular oxygen dissolved in plasma or interstitial tissue fluid. Therefore, well-oxygenated tissues show positive ΔR1. We hypothesized that the fraction of tumor tissue refractory to oxygen challenge (lack of positive ΔR1, termed “Oxy-R fraction”) would be a robust biomarker of hypoxia in models with varying vascular and hypoxic features. Here, we demonstrate that OE-MRI signals are accurate, precise, and sensitive to changes in tumor pO2 in highly vascular 786-0 renal cancer xenografts. Furthermore, we show that Oxy-R fraction can quantify the hypoxic fraction in multiple models with differing hypoxic and vascular phenotypes, when used in combination with measurements of tumor perfusion. Finally, Oxy-R fraction can detect dynamic changes in hypoxia induced by the vasomodulator agent hydralazine. In contrast, more conventional biomarkers of hypoxia (derived from blood oxygenation-level dependent MRI and dynamic contrast–enhanced MRI) did not relate to tumor hypoxia consistently. Our results show that the Oxy-R fraction accurately quantifies tumor hypoxia noninvasively and is immediately translatable to the clinic. Cancer Res; 76(4); 787–95. ©2015 AACR.

Published
2023

42. Physical activity and health-related quality of life in women with breast cancer: a meta-analysis

Author

Dagfinn Aune, Georgios Markozannes, Leila Abar, Katia Balducci, Margarita Cariolou, Neesha Nanu, Rita Vieira, Yusuf O Anifowoshe, Darren C Greenwood, Steven K Clinton, Edward L Giovannucci, Marc J Gunter, Alan Jackson, Ellen Kampman, Vivien Lund, Anne McTiernan, Elio Riboli, Kate Allen, Nigel T Brockton, Helen Croker, Daphne Katsikioti, Deirdre McGinley-Gieser, Panagiota Mitrou, Martin Wiseman, Galina Velikova, Wendy Demark-Wahnefried, Teresa Norat, Konstantinos K Tsilidis, and Doris S M Chan

Subjects
Cancer Research, Nutrition and Disease, Oncology, Voeding en Ziekte, Quality of Life, Humans, Life Science, Female, Breast Neoplasms, Exercise, VLAG
Abstract

Background Physical activity (PA) is associated with improved health-related quality of life (HRQoL) among women with breast cancer; however, uncertainty remains regarding PA types and dose (frequency, duration, intensity) and various HRQoL measures. A systematic review and meta-analysis of randomized controlled trials was conducted to clarify whether specific types and doses of physical activity was related to global and specific domains of HRQoL, as part of the Global Cancer Update Programme, formerly known as the World Cancer Research Fund–American Institute for Cancer Research Continuous Update Project. Methods PubMed and CENTRAL databases were searched up to August 31, 2019. Weighted mean differences (WMDs) in HRQoL scores were estimated using random effects models. An independent expert panel graded the evidence. Results A total of 79 randomized controlled trials (14 554 breast cancer patients) were included. PA interventions resulted in higher global HRQoL as measured by the Functional Assessment of Cancer Therapy–Breast (WMD = 5.94, 95% confidence intervals [CI] = 2.64 to 9.24; I2 = 59%, n = 12), Functional Assessment of Cancer Therapy–General (WMD = 4.53, 95% CI = 1.94 to 7.13; I2 = 72%, n = 18), and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–C30 (WMD = 6.78, 95% CI = 2.61 to 10.95; I2 = 76.3%, n = 17). The likelihood of causality was considered probable that PA improves HRQoL in breast cancer survivors. Effects were weaker for physical function and mental and emotional health. Evidence regarding dose and type of PA remains insufficient for firm conclusions. Conclusion PA results in improved global HRQoL in breast cancer survivors with weaker effects observed for physical function and mental and emotional health. Additional research is needed to define the impact of types and doses of activity on various domains of HRQoL.

Published
2022

48. Assessments in early growth of corn seedlings after hausmanite (Mn3O4) nanoscale seed priming

Author

Kyle Alan Jackson, Alessandro de Lucca e Braccini, Vitor Rodrigues Cordioli, Marcelo Augusto Batista, Michel Esper Neto, Tadeu Takeyoshi Inoue, Carolina Fedrigo Coneglian, and David W. Britt

Subjects
0106 biological sciences, Physiology, food and beverages, Biomass, 04 agricultural and veterinary sciences, Priming (agriculture), Biology, 01 natural sciences, Seed priming, Nutrient, Agronomy, 040103 agronomy & agriculture, 0401 agriculture, forestry, and fisheries, Seeding, Agronomy and Crop Science, Plant nutrition, 010606 plant biology & botany
Abstract

Nanofertilizer application is becoming a sustainable alternative for plants micronutrients supply. Seed nutrient priming before seeding reduces non-target dispersion; although, applying nanofertili...

Published
2021

49. Early growth of corn seedlings after seed priming with magnetite nanoparticles synthetised in easy way

Author

Kyle Alan Jackson, Michel Esper Neto, Marcelo Augusto Batista, David W. Britt, Carolina Fedrigo Coneglian, and Tadeu Takeyoshi Inoue

Subjects
0303 health sciences, Chemistry, Soil Science, Nanoparticle, 02 engineering and technology, 021001 nanoscience & nanotechnology, Seed priming, 03 medical and health sciences, Horticulture, Magnetite Nanoparticles, Phytotoxicity, 0210 nano-technology, Agronomy and Crop Science, 030304 developmental biology
Abstract

Nanoparticle (NP) use is becoming important alternative in different branches of science such as in agriculture, used as new source of fertiliser. In this study, it was tested iron (Fe) NP, applied...

Published
2020

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