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102. Weisfeiler and Leman go sparse: Towards scalable higher-order graph embeddings

Author

Morris, Christopher, Rattan, Gaurav, and Mutzel, Petra

Subjects
Computer Science - Data Structures and Algorithms, Computer Science - Discrete Mathematics, Statistics - Machine Learning
Abstract

Graph kernels based on the $1$-dimensional Weisfeiler-Leman algorithm and corresponding neural architectures recently emerged as powerful tools for (supervised) learning with graphs. However, due to the purely local nature of the algorithms, they might miss essential patterns in the given data and can only handle binary relations. The $k$-dimensional Weisfeiler-Leman algorithm addresses this by considering $k$-tuples, defined over the set of vertices, and defines a suitable notion of adjacency between these vertex tuples. Hence, it accounts for the higher-order interactions between vertices. However, it does not scale and may suffer from overfitting when used in a machine learning setting. Hence, it remains an important open problem to design WL-based graph learning methods that are simultaneously expressive, scalable, and non-overfitting. Here, we propose local variants and corresponding neural architectures, which consider a subset of the original neighborhood, making them more scalable, and less prone to overfitting. The expressive power of (one of) our algorithms is strictly higher than the original algorithm, in terms of ability to distinguish non-isomorphic graphs. Our experimental study confirms that the local algorithms, both kernel and neural architectures, lead to vastly reduced computation times, and prevent overfitting. The kernel version establishes a new state-of-the-art for graph classification on a wide range of benchmark datasets, while the neural version shows promising performance on large-scale molecular regression tasks., Comment: Accepted at NeurIPS 2020, extented version with proofs

Published
2019

103. A Survey on Graph Kernels

Author

Kriege, Nils M., Johansson, Fredrik D., and Morris, Christopher

Subjects
Computer Science - Machine Learning, Statistics - Machine Learning
Abstract

Graph kernels have become an established and widely-used technique for solving classification tasks on graphs. This survey gives a comprehensive overview of techniques for kernel-based graph classification developed in the past 15 years. We describe and categorize graph kernels based on properties inherent to their design, such as the nature of their extracted graph features, their method of computation and their applicability to problems in practice. In an extensive experimental evaluation, we study the classification accuracy of a large suite of graph kernels on established benchmarks as well as new datasets. We compare the performance of popular kernels with several baseline methods and study the effect of applying a Gaussian RBF kernel to the metric induced by a graph kernel. In doing so, we find that simple baselines become competitive after this transformation on some datasets. Moreover, we study the extent to which existing graph kernels agree in their predictions (and prediction errors) and obtain a data-driven categorization of kernels as result. Finally, based on our experimental results, we derive a practitioner's guide to kernel-based graph classification.

Published
2019
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104. Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias

Author

Soltis, Anthony R., Viollet, Coralie, Sukumar, Gauthaman, Alba, Camille, Lott, Nathaniel, McGrath Martinez, Elisa, Tuck, Meila, Singh, Jatinder, Bacikova, Dagmar, Zhang, Xijun, Hupalo, Daniel N., Adeleye, Adelani, Wilkerson, Matthew D., Pollard, Harvey B., Dalgard, Clifton L., Black, Sandra E., Gan-Or, Ziv, Keith, Julia, Masellis, Mario, Rogaeva, Ekaterina, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Calvo, Andrea, Canosa, Antonio, Chio, Adriano, Logroscino, Giancarlo, Mora, Gabriele, Krüger, Reijko, May, Patrick, Alcolea, Daniel, Clarimon, Jordi, Fortea, Juan, Gonzalez-Aramburu, Isabel, Infante, Jon, Lage, Carmen, Lleó, Alberto, Pastor, Pau, Sanchez-Juan, Pascual, Brett, Francesca, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Gentleman, Steve, Hardy, John A., Hodges, Angela K., Love, Seth, McKeith, Ian G., Morris, Christopher M., Morris, Huw R., Palmer, Laura, Pickering-Brown, Stuart, Ryten, Mina, Thomas, Alan J., Troakes, Claire, Albert, Marilyn S., Barrett, Matthew J., Beach, Thomas G., Bekris, Lynn M., Bennett, David A., Boeve, Bradley F., Dawson, Ted M., Dickson, Dennis W., Faber, Kelley, Ferman, Tanis, Ferrucci, Luigi, Flanagan, Margaret E., Foroud, Tatiana M., Ghetti, Bernardino, Gibbs, J. Raphael, Goate, Alison, Goldstein, David S., Graff-Radford, Neill R., Kaufmann, Horacio, Kukull, Walter A., Leverenz, James B., Lopez, Grisel, Mao, Qinwen, Masliah, Eliezer, Monuki, Edwin, Newell, Kathy L., Palma, Jose-Alberto, Perkins, Matthew, Pletnikova, Olga, Renton, Alan E., Resnick, Susan M., Rosenthal, Liana S., Ross, Owen A., Scherzer, Clemens R., Serrano, Geidy E., Shakkottai, Vikram G., Sidransky, Ellen, Tanaka, Toshiko, Tayebi, Nahid, Topol, Eric, Torkamani, Ali, Troncoso, Juan C., Woltjer, Randy, Wszolek, Zbigniew K., Scholz, Sonja W., Baloh, Robert H., Bowser, Robert, Broach, James, Camu, William, Chiò, Adriano, Cooper-Knock, John, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Feldman, Eva, Fratta, Pietro, Gerhard, Glenn, Gibson, Summer B., Glass, Jonathan D., Harms, Matthew B., Heiman-Patterson, Terry D., Jansson, Lilja, Kirby, Janine, Kwan, Justin, Laaksovirta, Hannu, Landers, John E., Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J.L., Maragakis, Nicholas J., Mouzat, Kevin, Myllykangas, Liisa, Orrell, Richard W., Ostrow, Lyle W., Pamphlett, Roger, Pioro, Erik, Pulst, Stefan M., Ravits, John M., Robberecht, Wim, Rothstein, Jeffrey D., Sendtner, Michael, Shaw, Pamela J., Sidle, Katie C., Simmons, Zachary, Stein, Thor, Stone, David J., Tienari, Pentti J., Traynor, Bryan J., Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M., Van Den Bosch, Ludo, Zinman, Lorne, Kaivola, Karri, Chia, Ruth, Ding, Jinhui, Rasheed, Memoona, Fujita, Masashi, Menon, Vilas, Walton, Ronald L., Collins, Ryan L., Billingsley, Kimberley, Brand, Harrison, Talkowski, Michael, Zhao, Xuefang, Dewan, Ramita, Stark, Ali, Ray, Anindita, Solaiman, Sultana, Alvarez Jerez, Pilar, Malik, Laksh, Tienari, Pentti, Mazzini, Letizia, D'Alfonso, Sandra, Moglia, Cristina, and De Jager, Philip L.

Published
2023
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106. Prioritization of Drug Targets for Neurodegenerative Diseases by Integrating Genetic and Proteomic Data From Brain and Blood

Author

Ferrari, Raffaele, Hernandez, Dena G., Nalls, Michael A., Rohrer, Jonathan D., Ramasamy, Adaikalavan, Kwok, John B.J., Dobson-Stone, Carol, Brooks, William S., Schofield, Peter R., Halliday, Glenda M., Hodges, John R., Piguet, Olivier, Bartley, Lauren, Thompson, Elizabeth, Haan, Eric, Hernández, Isabel, Ruiz, Agustín, Boada, Mercè, Borroni, Barbara, Padovani, Alessandro, Cruchaga, Carlos, Cairns, Nigel J., Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Forloni, Gianluigi, Galimberti, Daniela, Fenoglio, Chiara, Serpente, Maria, Scarpini, Elio, Clarimón, Jordi, Lleó, Alberto, Blesa, Rafael, Waldö, Maria Landqvist, Nilsson, Karin, Nilsson, Christer, Mackenzie, Ian R.A., Hsiung, Ging-Yuek R., Mann, David M.A., Grafman, Jordan, Morris, Christopher M., Attems, Johannes, Griffiths, Timothy D., McKeith, Ian G., Thomas, Alan J., Pietrini, P., Huey, Edward D., Wassermann, Eric M., Baborie, Atik, Jaros, Evelyn, Tierney, Michael C., Pastor, Pau, Razquin, Cristina, Ortega-Cubero, Sara, Alonso, Elena, Perneczky, Robert, Diehl-Schmid, Janine, Alexopoulos, Panagiotis, Kurz, Alexander, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Rogaeva, Ekaterina, St. George-Hyslop, Peter, Rossi, Giacomina, Tagliavini, Fabrizio, Giaccone, Giorgio, Rowe, James B., Schlachetzki, Johannes C.M., Uphill, James, Collinge, John, Mead, Simon, Danek, Adrian, Van Deerlin, Vivianna M., Grossman, Murray, Trojanowski, John Q., van der Zee, Julie, Deschamps, William, Van Langenhove, Tim, Cruts, Marc, Van Broeckhoven, Christine, Cappa, Stefano F., Le Ber, Isabelle, Hannequin, Didier, Golfier, Véronique, Vercelletto, Martine, Brice, Alexis, Nacmias, Benedetta, Sorbi, Sandro, Bagnoli, Silvia, Piaceri, Irene, Nielsen, Jørgen E., Hjermind, Lena E., Riemenschneider, Matthias, Mayhaus, Manuel, Ibach, Bernd, Gasparoni, Gilles, Pichler, Sabrina, Gu, Wei, Rossor, Martin N., Fox, Nick C., Warren, Jason D., Spillantini, Maria Grazia, Morris, Huw R., Rizzu, Patrizia, Heutink, Peter, Snowden, Julie S., Rollinson, Sara, Richardson, Anna, Gerhard, Alexander, Bruni, Amalia C., Maletta, Raffaele, Frangipane, Francesca, Cupidi, Chiara, Bernardi, Livia, Anfossi, Maria, Gallo, Maura, Conidi, Maria Elena, Smirne, Nicoletta, Rademakers, Rosa, Baker, Matt, Dickson, Dennis W., Graff-Radford, Neill R., Petersen, Ronald C., Knopman, David, Josephs, Keith A., Boeve, Bradley F., Parisi, Joseph E., Seeley, William W., Miller, Bruce L., Karydas, Anna M., Rosen, Howard, van Swieten, John C., Dopper, Elise G.P., Seelaar, Harro, Pijnenburg, Yolande A.L., Scheltens, Philip, Logroscino, Giancarlo, Capozzo, Rosa, Novelli, Valeria, Puca, Annibale A., Franceschi, Massimo, Postiglione, Alfredo, Milan, Graziella, Sorrentino, Paolo, Kristiansen, Mark, Chiang, Huei-Hsin, Graff, Caroline, Pasquier, Florence, Rollin, Adeline, Deramecourt, Vincent, Lebert, Florence, Kapogiannis, Dimitrios, Ferrucci, Luigi, Pickering-Brown, Stuart, Singleton, Andrew B., Hardy, John, Momeni, Parastoo, Ge, Yi-Jun, Ou, Ya-Nan, Deng, Yue-Ting, Wu, Bang-Sheng, Yang, Liu, Zhang, Ya-Ru, Chen, Shi-Dong, Huang, Yu-Yuan, Dong, Qiang, Tan, Lan, and Yu, Jin-Tai

Published
2023
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107. Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.

Author

van der Lee, Sven J, Conway, Olivia J, Jansen, Iris, Carrasquillo, Minerva M, Kleineidam, Luca, van den Akker, Erik, Hernández, Isabel, van Eijk, Kristel R, Stringa, Najada, Chen, Jason A, Zettergren, Anna, Andlauer, Till FM, Diez-Fairen, Monica, Simon-Sanchez, Javier, Lleó, Alberto, Zetterberg, Henrik, Nygaard, Marianne, Blauwendraat, Cornelis, Savage, Jeanne E, Mengel-From, Jonas, Moreno-Grau, Sonia, Wagner, Michael, Fortea, Juan, Keogh, Michael J, Blennow, Kaj, Skoog, Ingmar, Friese, Manuel A, Pletnikova, Olga, Zulaica, Miren, Lage, Carmen, de Rojas, Itziar, Riedel-Heller, Steffi, Illán-Gala, Ignacio, Wei, Wei, Jeune, Bernard, Orellana, Adelina, Then Bergh, Florian, Wang, Xue, Hulsman, Marc, Beker, Nina, Tesi, Niccolo, Morris, Christopher M, Indakoetxea, Begoña, Collij, Lyduine E, Scherer, Martin, Morenas-Rodríguez, Estrella, Ironside, James W, van Berckel, Bart NM, Alcolea, Daniel, Wiendl, Heinz, Strickland, Samantha L, Pastor, Pau, Rodríguez Rodríguez, Eloy, DESGESCO (Dementia Genetics Spanish Consortium), EADB (Alzheimer Disease European DNA biobank), IFGC (International FTD-Genomics Consortium), IPDGC (The International Parkinson Disease Genomics Consortium), RiMod-FTD (Risk and Modifying factors in Fronto-Temporal Dementia), Netherlands Brain Bank (NBB), Boeve, Bradley F, Petersen, Ronald C, Ferman, Tanis J, van Gerpen, Jay A, Reinders, Marcel JT, Uitti, Ryan J, Tárraga, Lluís, Maier, Wolfgang, Dols-Icardo, Oriol, Kawalia, Amit, Dalmasso, Maria Carolina, Boada, Mercè, Zettl, Uwe K, van Schoor, Natasja M, Beekman, Marian, Allen, Mariet, Masliah, Eliezer, de Munain, Adolfo López, Pantelyat, Alexander, Wszolek, Zbigniew K, Ross, Owen A, Dickson, Dennis W, Graff-Radford, Neill R, Knopman, David, Rademakers, Rosa, Lemstra, Afina W, Pijnenburg, Yolande AL, Scheltens, Philip, Gasser, Thomas, Chinnery, Patrick F, Hemmer, Bernhard, Huisman, Martijn A, Troncoso, Juan, Moreno, Fermin, Nohr, Ellen A, Sørensen, Thorkild IA, Heutink, Peter, Sánchez-Juan, Pascual, Posthuma, Danielle, GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group, and Clarimón, Jordi

Subjects
DESGESCO, EADB, IFGC, IPDGC, RiMod-FTD, Netherlands Brain Bank, GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group, Acquired Cognitive Impairment, Brain Disorders, Neurodegenerative, Alzheimer's Disease, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Aging, Parkinson's Disease, Genetics, 2.1 Biological and endogenous factors, Neurological, Neurology & Neurosurgery, Clinical Sciences
Abstract

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once.

Published
2020

108. Society of Interventional Radiology Position Statement on the Role of Percutaneous Ablation in Renal Cell Carcinoma: Endorsed by the Canadian Association for Interventional Radiology and the Society of Interventional Oncology.

Author

Morris, Christopher S, Baerlocher, Mark O, Dariushnia, Sean R, McLoney, Eric D, Abi-Jaoudeh, Nadine, Nelson, Kari, Cura, Marco, Abdel Aal, Ahmed Kamel, Mitchell, Jason W, Madassery, Sreekumar, Partovi, Sasan, McClure, Timothy D, Tam, Alda L, and Patel, Sheena

Subjects
Humans, Carcinoma, Renal Cell, Kidney Neoplasms, Radiography, Interventional, Treatment Outcome, Cryosurgery, Tumor Burden, Risk Assessment, Risk Factors, Consensus, Microwaves, Patient Selection, Clinical Decision-Making, Radiofrequency Ablation, Clinical Sciences, Nuclear Medicine & Medical Imaging
Published
2020

109. Weisfeiler and Leman Go Neural: Higher-order Graph Neural Networks

Author

Morris, Christopher, Ritzert, Martin, Fey, Matthias, Hamilton, William L., Lenssen, Jan Eric, Rattan, Gaurav, and Grohe, Martin

Subjects
Computer Science - Machine Learning, Computer Science - Artificial Intelligence, Computer Science - Computer Vision and Pattern Recognition, Computer Science - Neural and Evolutionary Computing, Statistics - Machine Learning
Abstract

In recent years, graph neural networks (GNNs) have emerged as a powerful neural architecture to learn vector representations of nodes and graphs in a supervised, end-to-end fashion. Up to now, GNNs have only been evaluated empirically -- showing promising results. The following work investigates GNNs from a theoretical point of view and relates them to the $1$-dimensional Weisfeiler-Leman graph isomorphism heuristic ($1$-WL). We show that GNNs have the same expressiveness as the $1$-WL in terms of distinguishing non-isomorphic (sub-)graphs. Hence, both algorithms also have the same shortcomings. Based on this, we propose a generalization of GNNs, so-called $k$-dimensional GNNs ($k$-GNNs), which can take higher-order graph structures at multiple scales into account. These higher-order structures play an essential role in the characterization of social networks and molecule graphs. Our experimental evaluation confirms our theoretical findings as well as confirms that higher-order information is useful in the task of graph classification and regression., Comment: Extended version with proofs, accepted at AAAI 2019, added units of measurement of QM9 dataset into appendix, removed results from Wu et al., 2018 due to different units

Published
2018

111. C9orf72 intermediate repeats are associated with corticobasal degeneration, increased C9orf72 expression and disruption of autophagy

Author

Cali, Christopher P, Patino, Maribel, Tai, Yee Kit, Ho, Wan Yun, McLean, Catriona A, Morris, Christopher M, Seeley, William W, Miller, Bruce L, Gaig, Carles, Vonsattel, Jean Paul G, White, Charles L, Roeber, Sigrun, Kretzschmar, Hans, Troncoso, Juan C, Troakes, Claire, Gearing, Marla, Ghetti, Bernardino, Van Deerlin, Vivianna M, Lee, Virginia M-Y, Trojanowski, John Q, Mok, Kin Y, Ling, Helen, Dickson, Dennis W, Schellenberg, Gerard D, Ling, Shuo-Chien, and Lee, Edward B

Subjects
Biomedical and Clinical Sciences, Neurosciences, Genetics, Rare Diseases, Acquired Cognitive Impairment, Aging, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), ALS, Neurodegenerative, Alzheimer's Disease Related Dementias (ADRD), Frontotemporal Dementia (FTD), Dementia, Stem Cell Research, 2.1 Biological and endogenous factors, Aetiology, Neurological, Alzheimer Disease, Amyotrophic Lateral Sclerosis, Autophagy, Basal Ganglia Diseases, Brain, C9orf72 Protein, Frontotemporal Dementia, Humans, Neurodegenerative Diseases, Parkinson Disease, Parkinsonian Disorders, Neurodegeneration, Corticobasal degeneration, C9orf72 repeat expansion, Parkinsonism, Clinical Sciences, Neurology & Neurosurgery
Abstract

Microsatellite repeat expansion disease loci can exhibit pleiotropic clinical and biological effects depending on repeat length. Large expansions in C9orf72 (100s-1000s of units) are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). However, whether intermediate expansions also contribute to neurodegenerative disease is not well understood. Several studies have identified intermediate repeats in Parkinson's disease patients, but the association was not found in autopsy-confirmed cases. We hypothesized that intermediate C9orf72 repeats are a genetic risk factor for corticobasal degeneration (CBD), a neurodegenerative disease that can be clinically similar to Parkinson's but has distinct tau protein pathology. Indeed, intermediate C9orf72 repeats were significantly enriched in autopsy-proven CBD (n = 354 cases, odds ratio = 3.59, p = 0.00024). While large C9orf72 repeat expansions are known to decrease C9orf72 expression, intermediate C9orf72 repeats result in increased C9orf72 expression in human brain tissue and CRISPR/cas9 knockin iPSC-derived neural progenitor cells. In contrast to cases of FTD/ALS with large C9orf72 expansions, CBD with intermediate C9orf72 repeats was not associated with pathologic RNA foci or dipeptide repeat protein aggregates. Knock-in cells with intermediate repeats exhibit numerous changes in gene expression pathways relating to vesicle trafficking and autophagy. Additionally, overexpression of C9orf72 without the repeat expansion leads to defects in autophagy under nutrient starvation conditions. These results raise the possibility that therapeutic strategies to reduce C9orf72 expression may be beneficial for the treatment of CBD.

Published
2019

112. Anti–Cholestatic Therapy with Obeticholic Acid Improves Short-Term Memory in Bile Duct–Ligated Mice

Author

Gee, Lucy M.V., Barron-Millar, Ben, Leslie, Jack, Richardson, Claire, Zaki, Marco Y.W., Luli, Saimir, Burgoyne, Rachel A., Cameron, Rainie I.T., Smith, Graham R., Brain, John G., Innes, Barbara, Jopson, Laura, Dyson, Jessica K., McKay, Katherine R.C., Pechlivanis, Alexandros, Holmes, Elaine, Berlinguer-Palmini, Rolando, Victorelli, Stella, Mells, George F., Sandford, Richard N., Palmer, Jeremy, Kirby, John A., Kiourtis, Christos, Mokochinski, Joao, Hall, Zoe, Bird, Thomas G., Borthwick, Lee A., Morris, Christopher M., Hanson, Peter S., Jurk, Diana, Stoll, Elizabeth A., LeBeau, Fiona E.N., Jones, David E.J., and Oakley, Fiona

Published
2023
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114. 4 Structured Data

Author

Piatkowski, Nico, primary, Morik, Katharina, additional, Kriege, Nils, additional, Morris, Christopher, additional, Fey, Matthias, additional, Weichert, Frank, additional, Bertram, Nico, additional, Ellert, Jonas, additional, Fischer, Johannes, additional, and Pfahler, Lukas, additional

Published
2022
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115. PP2A modulation overcomes multidrug resistance in chronic lymphocytic leukemia via mPTP-dependent apoptosis

Author

Jayappa, Kallesh D., Tran, Brian, Gordon, Vicki L., Morris, Christopher, Saha, Shekhar, Farrington, Caroline C., O'Connor, Caitlin M., Zawacki, Kaitlin P., Isaac, Krista M., Kester, Mark, Bender, Timothy P., Williams, Michael E., Portell, Craig A., Weber, Michael J., and Narla, Goutham

Subjects
Mitochondrial membranes -- Physiological aspects -- Health aspects, Drug resistance -- Physiological aspects, Phosphatases -- Physiological aspects -- Health aspects, Chronic lymphocytic leukemia -- Drug therapy -- Development and progression, Apoptosis -- Health aspects, Health care industry
Abstract

Targeted therapies such as venetoclax (VEN) (Bcl-2 inhibitor) have revolutionized the treatment of chronic lymphocytic leukemia (CLL). We previously reported that persister CLL cells in treated patients overexpress multiple antiapoptotic proteins and display resistance to proapoptotic agents. Here, we demonstrated that multidrug-resistant CLL cells in vivo exhibited apoptosis restriction at a pre-mitochondrial level due to insufficient activation of the Bax and Bak (Bax/Bak) proteins. Co-immunoprecipitation analyses with selective BH domain antagonists revealed that the pleiotropic proapoptotic protein (Bim) was prevented from activating Bax/Bak by 'switching' interactions to other upregulated antiapoptotic proteins (Mcl-1, Bcl-xL, Bcl-2). Hence, treatments that bypass Bax/Bak restriction are required to deplete these resistant cells in patients. Protein phosphatase 2A (PP2A) contributes to oncogenesis and treatment resistance. We observed that small-molecule activator of PP2A (SMAP) induced cytotoxicity in multiple cancer cell lines and CLL samples, including multidrug-resistant leukemia and lymphoma cells. The SMAP (DT-061) activated apoptosis in multidrug-resistant CLL cells through induction of mitochondrial permeability transition pores, independent of Bax/Bak. DT-061 inhibited the growth of wild-type and Bax/Bak doubleknockout, multidrug-resistant CLL cells in a xenograft mouse model. Collectively, we discovered multidrug-resistant CLL cells in patients and validated a pharmacologically tractable pathway to deplete this reservoir., Introduction The introduction of proapoptotic pharmacological agents such as the antiapoptotic protein Bcl-2 inhibitor VEN has revolutionized the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Although [...]

Published
2023
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116. Contemporary religious conflicts and the law of armed conflict : an analysis of the challenges posed by ISIS and other 'unconventional armed groups'

Author

Morris, Christopher, Badar, Mohamed, and Wyatt, Tanya

Subjects
341.6, L900 Others in Social studies, M100 Law by area, M200 Law by Topic, M900 Other in Law, V600 Theology and Religious studies
Abstract

This thesis introduces and develops the idea of “contemporary religious conflict”. It proposes that international humanitarian law (IHL) should incorporate an understanding of religious approaches to the use of force in order to better address the shortfall of humanitarian protections that have become typical of conflicts involving “unconventional armed groups”. Due to this shortfall having a relationship with what may be termed the “war on terror”, the intention is to focus explicitly upon the capacity for religious ideology to influence how force is used, and how IHL should address this challenge. Contemporary religious conflict is not introduced as a new category of armed conflict intended to supplement those already existing in IHL, but as a means of better balancing the use of force with humanitarian concerns by acknowledging the deterministic influence the adoption of religious features may have upon how an armed group uses force. A distinct framework for understanding conflicts with a religious component provides a more nuanced method for balancing state interests with humanitarian principles. This thesis accordingly sets out to determine how religious conflicts function differently from non-religious conflicts, and to what extent these differences challenge the assumptions concerning the use of force inherent in IHL. In order to determine how IHL may adapt to these stresses, this thesis will draw upon both historic and present-day approaches to religious conflict, as well as contemporary state practice in conflicts involving religious interest groups, with an overt focus upon key current examples such as ISIS.1 Whilst IHL has conventionally been disinterested in the rationale behind armed conflicts, acknowledging that the adoption of religious ideology can have a causal relationship with how force is used permits shareholders in IHL to more effectively determine their role in limiting the adverse implications of armed conflict, and ensuring humanitarian principles are applied in an appropriate manner. This study depends upon contemporary examples of religious conflict, necessitating a focus upon examples derived from the Islamic tradition, largely within the context of what is frequently termed the “war on terror”. Whilst this study explicitly focuses upon central examples such as ISIS, the intent is to propose a general basis for a differentiated understanding of religious conflict applicable in a wider range of instances.

Published
2019

117. Protein precipitation for the purification of therapeutic protein

Author

Morris, Christopher W.

Subjects
660
Abstract

This thesis documents the application of precipitant scouting and analytical tools for the development of a precipitation process for the purification of therapeutic proteins in biopharmaceuticals. Precipitation has the potential to bypass the bottlenecks in productivity experienced with packed bed chromatographic separations, offering a fast, robust first purification step with volume reduction at low cost. In order to evaluate a large number of precipitation candidates, microscale investigations aided by automated liquid handling robotics were chosen, which conferred precision, speed, and complex experimental design with microliter material requirements and in-line analytics. A precipitation screening methodology was successfully built onto a Tecan liquid handling platform including product recovery and techniques for measuring soluble protein, liquid volumes, and recovered protein precipitate. The protocol was supplemented with a custombuild Excel VBA driven Tecan control tool. This accelerated progress by freeing up the potential of the liquid handling arm, which was curtailed by system software. These techniques were then used to characterise effective precipitants for the purification of monoclonal antibodies. Optimal conditions were identified on pure protein models, which were the bridged to process relevant cell culture fluid. Process performance, notably recovery yield and product quality were the investigated on the precipitant conditions brought forward. Process integration aspects were explored, by linking precipitation with an anion exchange chromatography step. This led to discussion on future work and process scale up considerations.

Published
2019

120. MAPT H2 haplotype and risk of Pick's disease in the Pick's disease International Consortium: a genetic association study

Author

Valentino, Rebecca R, primary, Scotton, William J, additional, Roemer, Shanu F, additional, Lashley, Tammaryn, additional, Heckman, Michael G, additional, Shoai, Maryam, additional, Martinez-Carrasco, Alejandro, additional, Tamvaka, Nicole, additional, Walton, Ronald L, additional, Baker, Matthew C, additional, Macpherson, Hannah L, additional, Real, Raquel, additional, Soto-Beasley, Alexandra I, additional, Mok, Kin, additional, Revesz, Tamas, additional, Christopher, Elizabeth A, additional, DeTure, Michael, additional, Seeley, William W, additional, Lee, Edward B, additional, Frosch, Matthew P, additional, Molina-Porcel, Laura, additional, Gefen, Tamar, additional, Redding-Ochoa, Javier, additional, Ghetti, Bernardino, additional, Robinson, Andrew C, additional, Kobylecki, Christopher, additional, Rowe, James B, additional, Beach, Thomas G, additional, Teich, Andrew F, additional, Keith, Julia L, additional, Bodi, Istvan, additional, Halliday, Glenda M, additional, Gearing, Marla, additional, Arzberger, Thomas, additional, Morris, Christopher M, additional, White, Charles L, additional, Mechawar, Naguib, additional, Boluda, Susana, additional, MacKenzie, Ian R, additional, McLean, Catriona, additional, Cykowski, Matthew D, additional, Wang, Shih-Hsiu J, additional, Graff, Caroline, additional, Nagra, Rashed M, additional, Kovacs, Gabor G, additional, Giaccone, Giorgio, additional, Neumann, Manuela, additional, Ang, Lee-Cyn, additional, Carvalho, Agostinho, additional, Morris, Huw R, additional, Rademakers, Rosa, additional, Hardy, John A, additional, Dickson, Dennis W, additional, Rohrer, Jonathan D, additional, Ross, Owen A, additional, Warner, Thomas T, additional, Jaunmuktane, Zane, additional, Boeve, Bradley F, additional, Duara, Ranjan, additional, Graff-Radford, Neill R, additional, Josephs, Keith A, additional, Knopman, David S, additional, Koga, Shunsuke, additional, Murray, Melissa E, additional, Lyons, Kelly E, additional, Pahwa, Rajesh, additional, Petersen, Ronald C, additional, Whitwell, Jennifer L, additional, Grinberg, Lea T, additional, Miller, Bruce, additional, Schlereth, Athena, additional, Spina, Salvatore, additional, Grossman, Murray, additional, Irwin, David J, additional, Suh, EunRan, additional, Trojanowski, John Q, additional, Van Deerlin, Vivianna M, additional, Wolk, David A, additional, Connors, Theresa R, additional, Dooley, Patrick M, additional, Oakley, Derek H, additional, Aldecoa, Iban, additional, Balasa, Mircea, additional, Gelpi, Ellen, additional, Borrego-Écija, Sergi, additional, Gascon-Bayarri, Jordi, additional, Sánchez-Valle, Raquel, additional, Sanz-Cartagena, Pilar, additional, Piñol-Ripoll, Gerard, additional, Bigio, Eileen H, additional, Flanagan, Margaret E, additional, Rogalski, Emily J, additional, Weintraub, Sandra, additional, Schneider, Julie A, additional, Peng, Lihua, additional, Zhu, Xiongwei, additional, Chang, Koping, additional, Troncoso, Juan C, additional, Prokop, Stefan, additional, Newell, Kathy L, additional, Jones, Matthew, additional, Richardson, Anna, additional, Roncaroli, Federico, additional, Snowden, Julie, additional, Allinson, Kieren, additional, Singh, Poonam, additional, Serrano, Geidy E, additional, Flowers, Xena E, additional, Goldman, James E, additional, Heaps, Allison C, additional, Leskinen, Sandra P, additional, Black, Sandra E, additional, Masellis, Mario, additional, King, Andrew, additional, Al-Sarraj, Safa, additional, Troakes, Claire, additional, Hodges, John R, additional, Kril, Jillian J, additional, Kwok, John B, additional, Piguet, Olivier, additional, Roeber, Sigrun, additional, Attems, Johannes, additional, Thomas, Alan J, additional, Evers, Bret M., additional, Bieniek, Kevin F, additional, Sieben, Anne A, additional, Cras, Patrick P, additional, De Vil, Bart B, additional, Bird, Thomas, additional, Castellani, Rudolph J, additional, Chaffee, Ann, additional, Franklin, Erin, additional, Haroutunian, Vahram, additional, Jacobsen, Max, additional, Keene, Dirk, additional, Latimer, Caitlin S, additional, Metcalf, Jeff, additional, Perrin, Richard J, additional, Purohit, Dushyant P, additional, Rissman, Robert A, additional, Schantz, Aimee, additional, Walker, Jamie, additional, De Deyn, Peter P, additional, Duyckaerts, Charles, additional, Le Ber, Isabelle, additional, Seilhean, Danielle, additional, Turbant-Leclere, Sabrina, additional, Ervin, John F, additional, Nennesmo, Inger, additional, Riehl, James, additional, Nacmias, Benedetta, additional, Finger, Elizabeth C, additional, Blauwendraat, Cornelis, additional, Nalls, Mike A, additional, Singleton, Andrew B, additional, Vitale, Dan, additional, Cunha, Cristina, additional, and Wszolek, Zbigniew K, additional

Published
2024
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123. Hierarchical Graph Representation Learning with Differentiable Pooling

Author

Ying, Rex, You, Jiaxuan, Morris, Christopher, Ren, Xiang, Hamilton, William L., and Leskovec, Jure

Subjects
Computer Science - Machine Learning, Computer Science - Neural and Evolutionary Computing, Computer Science - Social and Information Networks, Statistics - Machine Learning
Abstract

Recently, graph neural networks (GNNs) have revolutionized the field of graph representation learning through effectively learned node embeddings, and achieved state-of-the-art results in tasks such as node classification and link prediction. However, current GNN methods are inherently flat and do not learn hierarchical representations of graphs---a limitation that is especially problematic for the task of graph classification, where the goal is to predict the label associated with an entire graph. Here we propose DiffPool, a differentiable graph pooling module that can generate hierarchical representations of graphs and can be combined with various graph neural network architectures in an end-to-end fashion. DiffPool learns a differentiable soft cluster assignment for nodes at each layer of a deep GNN, mapping nodes to a set of clusters, which then form the coarsened input for the next GNN layer. Our experimental results show that combining existing GNN methods with DiffPool yields an average improvement of 5-10% accuracy on graph classification benchmarks, compared to all existing pooling approaches, achieving a new state-of-the-art on four out of five benchmark data sets.

Published
2018

124. 3D Cosmic Ray Muon Tomography from an Underground Tunnel

Author

Guardincerri, Elena, Rowe, Charlotte, Schultz-Fellenz, Emily, Roy, Mousumi, George, Nicolas, Morris, Christopher, Bacon, Jeffrey, Durham, Matthew, Morley, Deborah, Plaud-Ramos, Kenie, Poulson, Daniel, Bonneville, Alain, and Kouzes, Richard

Subjects
Physics - Geophysics, Physics - Applied Physics
Abstract

We present an underground cosmic ray muon tomographic experiment imaging 3D density of overburden, part of a joint study with differential gravity. Muon data were acquired at four locations within a tunnel beneath Los Alamos, New Mexico, and used in a 3D tomographic inversion to recover the spatial variation in the overlying rock-air interface, and compared with a priori knowledge of the topography. Densities obtained exhibit good agreement with preliminary results of the gravity modeling, which will be presented elsewhere, and are compatible with values reported in the literature. The modeled rock-air interface matches that obtained from LIDAR within 4 m, our resolution, over much of the model volume. This experiment demonstrates the power of cosmic ray muons to image shallow geological targets using underground detectors, whose development as borehole devices will be an important new direction of passive geophysical imaging., Comment: 17 pages, 8 figures

Published
2018
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125. A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.

Author

van der Lee, Sven J, Conway, Olivia J, Jansen, Iris, Carrasquillo, Minerva M, Kleineidam, Luca, van den Akker, Erik, Hernández, Isabel, van Eijk, Kristel R, Stringa, Najada, Chen, Jason A, Zettergren, Anna, Andlauer, Till FM, Diez-Fairen, Monica, Simon-Sanchez, Javier, Lleó, Alberto, Zetterberg, Henrik, Nygaard, Marianne, Blauwendraat, Cornelis, Savage, Jeanne E, Mengel-From, Jonas, Moreno-Grau, Sonia, Wagner, Michael, Fortea, Juan, Keogh, Michael J, Blennow, Kaj, Skoog, Ingmar, Friese, Manuel A, Pletnikova, Olga, Zulaica, Miren, Lage, Carmen, de Rojas, Itziar, Riedel-Heller, Steffi, Illán-Gala, Ignacio, Wei, Wei, Jeune, Bernard, Orellana, Adelina, Then Bergh, Florian, Wang, Xue, Hulsman, Marc, Beker, Nina, Tesi, Niccolo, Morris, Christopher M, Indakoetxea, Begoña, Collij, Lyduine E, Scherer, Martin, Morenas-Rodríguez, Estrella, Ironside, James W, van Berckel, Bart NM, Alcolea, Daniel, Wiendl, Heinz, Strickland, Samantha L, Pastor, Pau, Rodríguez Rodríguez, Eloy, DESGESCO (Dementia Genetics Spanish Consortium), EADB (Alzheimer Disease European DNA biobank), EADB (Alzheimer Disease European DNA biobank), IFGC (International FTD-Genomics Consortium), IPDGC (The International Parkinson Disease Genomics Consortium), IPDGC (The International Parkinson Disease Genomics Consortium), RiMod-FTD (Risk and Modifying factors in Fronto-Temporal Dementia), Netherlands Brain Bank (NBB), Boeve, Bradley F, Petersen, Ronald C, Ferman, Tanis J, van Gerpen, Jay A, Reinders, Marcel JT, Uitti, Ryan J, Tárraga, Lluís, Maier, Wolfgang, Dols-Icardo, Oriol, Kawalia, Amit, Dalmasso, Maria Carolina, Boada, Mercè, Zettl, Uwe K, van Schoor, Natasja M, Beekman, Marian, Allen, Mariet, Masliah, Eliezer, de Munain, Adolfo López, Pantelyat, Alexander, Wszolek, Zbigniew K, Ross, Owen A, Dickson, Dennis W, Graff-Radford, Neill R, Knopman, David, Rademakers, Rosa, Lemstra, Afina W, Pijnenburg, Yolande AL, Scheltens, Philip, Gasser, Thomas, Chinnery, Patrick F, Hemmer, Bernhard, Huisman, Martijn A, Troncoso, Juan, Moreno, Fermin, Nohr, Ellen A, Sørensen, Thorkild IA, Heutink, Peter, Sánchez-Juan, Pascual, Posthuma, Danielle, GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group, and Clarimón, Jordi

Subjects
DESGESCO (Dementia Genetics Spanish Consortium), EADB, EADB, IFGC (International FTD-Genomics Consortium), IPDGC, IPDGC, RiMod-FTD, Netherlands Brain Bank, GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group, Alzheimer’s disease, Amyotrophic lateral sclerosis, Dementia with Lewy bodies, Frontotemporal dementia, Longevity, Multiple sclerosis, Neurodegenerative disease, PLCG2, Parkinson’s disease, Phospholipase C Gamma 2, Progressive supranuclear palsy, Alzheimer's disease, Parkinson's disease, Alzheimer's Disease, frontotemporal dementia, dementia with Lewy-bodies, progressive suprauclear palsy, Parkinson's Disease, amyotrophic lateral sclerosis, multiple sclerosis, neurodegenerative disease, longevity, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.

Published
2019

126. Cartel conduct in waste disposal industry ends in criminal convictions

Author

Morris, Christopher

Subjects
Antitrust law -- Cases, Cartels -- Cases, Company legal issue, Antitrust issue, Business, international
Abstract

The words 'cartel conduct' usually bring to mind violent international drug crime gangs. But cartels can also mean you pay more when you renovate, repair or build a home, buy [...]

Published
2024

133. Data integration in the rail domain

Author

Morris, Christopher Robert

Subjects
625.100285, QA75 Electronic computers. Computer science, TF Railroad engineering and operation
Abstract

The exchange of information is crucial to the operation of railways; starting with the distribution of timetables, information must constantly be exchanged in any railway network. The slow evolution of the information environment within the rail industry has resulted in the existence of a diverse range of systems, only able to exchange information essential to railway operations. Were the cost of data integration reduced, then further cost reductions and improvements to customer service would follow as barriers to the adoption of other technologies are removed. The need for data integration has already been studied extensively and has been included in the UK industry's rail technical strategy however, despite it's identification as a key technique for improving integration, uptake of ontology remains limited. This thesis considers techniques to reduce barriers to the take up of ontology in the UK rail industry, and presents a case study in which these techniques are applied. Amongst the key barriers to uptake identified are a lack of software engineers with ontology experience, and the diverse information environment within the rail domain. Techniques to overcomes these barriers using software based tools are considered, and example tools produced which aid the overcoming of these barriers. The case study presented is of a degraded mode signalling system, drawing data from a range of diverse sources, integrated using an ontology. Tools created to improve data integration are employed in this commercial project, successfully combing signalling data with (simulated) train positioning data.

Published
2018

134. Global Weisfeiler-Lehman Graph Kernels

Author

Morris, Christopher, Kersting, Kristian, and Mutzel, Petra

Subjects
Computer Science - Learning, Statistics - Machine Learning
Abstract

Most state-of-the-art graph kernels only take local graph properties into account, i.e., the kernel is computed with regard to properties of the neighborhood of vertices or other small substructures. On the other hand, kernels that do take global graph propertiesinto account may not scale well to large graph databases. Here we propose to start exploring the space between local and global graph kernels, striking the balance between both worlds. Specifically, we introduce a novel graph kernel based on the $k$-dimensional Weisfeiler-Lehman algorithm. Unfortunately, the $k$-dimensional Weisfeiler-Lehman algorithm scales exponentially in $k$. Consequently, we devise a stochastic version of the kernel with provable approximation guarantees using conditional Rademacher averages. On bounded-degree graphs, it can even be computed in constant time. We support our theoretical results with experiments on several graph classification benchmarks, showing that our kernels often outperform the state-of-the-art in terms of classification accuracies., Comment: 10 pages, accepted at IEEE ICDM 2017 ("Glocalized Weisfeiler-Lehman Graph Kernels: Global-Local Feature Maps of Graphs")

Published
2017

135. A Unifying View of Explicit and Implicit Feature Maps of Graph Kernels

Author

Kriege, Nils M., Neumann, Marion, Morris, Christopher, Kersting, Kristian, and Mutzel, Petra

Subjects
Computer Science - Machine Learning, Statistics - Machine Learning
Abstract

Non-linear kernel methods can be approximated by fast linear ones using suitable explicit feature maps allowing their application to large scale problems. We investigate how convolution kernels for structured data are composed from base kernels and construct corresponding feature maps. On this basis we propose exact and approximative feature maps for widely used graph kernels based on the kernel trick. We analyze for which kernels and graph properties computation by explicit feature maps is feasible and actually more efficient. In particular, we derive approximative, explicit feature maps for state-of-the-art kernels supporting real-valued attributes including the GraphHopper and graph invariant kernels. In extensive experiments we show that our approaches often achieve a classification accuracy close to the exact methods based on the kernel trick, but require only a fraction of their running time. Moreover, we propose and analyze algorithms for computing random walk, shortest-path and subgraph matching kernels by explicit and implicit feature maps. Our theoretical results are confirmed experimentally by observing a phase transition when comparing running time with respect to label diversity, walk lengths and subgraph size, respectively.

Published
2017
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136. Restoration of Strength in Polyamide Woven Glass Fiber Organosheets by Hot Pressing: Case Study of Impact and Compression after Impact.

Author

Saquib, Mohammad Nazmus, Chaparro-Chavez, Edwing, Morris, Christopher, Çelebi, Kuthan, Pedrazzoli, Diego, Zhang, Mingfu, Kravchenko, Sergii G., and Kravchenko, Oleksandr G.

Subjects
ENERGY levels (Quantum mechanics), IMPACT response, DIGITAL image correlation, THERMOSETTING composites, NYLON fibers, THERMOPLASTIC composites
Abstract

Thermoplastic composite organosheets (OSs) are increasingly recognized as a viable solution for automotive and aerospace structures, offering a range of benefits including cost-effectiveness through high-rate production, lightweight design, impact resistance, formability, and recyclability. This study examines the impact response, post-impact strength evaluation, and hot-pressing repair effectiveness of woven glass fiber nylon composite OSs across varying impact energy levels. Experimental investigations involved subjecting composite specimens to impact at varying energy levels using a drop-tower test rig, followed by compression-after-impact (CAI) tests. The results underscore the exceptional damage tolerance and improved residual compressive strength of the OSs compared to traditional thermoset composites. This enhancement was primarily attributed to the matrix's ductility, which mitigated transverse crack propagation and significantly increased the amount of absorbed energy. To mitigate impact-induced damage, a localized hot-pressing repair approach was developed. This allowed to restore the post-impact strength of the OSs to pristine levels for impact energies below 40 J and by 83.6% for higher impact energies, when OS perforation was observed. The measured levels of post-repair strength demonstrate a successful restoration of OS strength over a wide range of impact energies, and despite limitations in achieving complete strength recovery above 40 J, hot-pressing repair emerges as a promising strategy for ensuring the longevity of thermoplastic composites through repairability. [ABSTRACT FROM AUTHOR]

Published
2024
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137. Effect of Post-Cured through Thickness Reinforcement on Disbonding Behavior in Skin–Stringer Configuration.

Author

Bhagatji, Jimesh D., Morris, Christopher, Sridhar, Yogaraja, Bhattacharjee, Bodhisatwa, Kaipa, Krishnanand N., and Kravchenko, Oleksandr G.

Subjects
*FINITE element method, *FAILURE mode & effects analysis, *LAMINATED materials, *ADHESIVES
Abstract

An experimental investigation of interlaminar toughness for post-cured through-thickness reinforcement (PTTR) skin–stringer sub-element is presented. The improvement in the crack resistance capability of skin–stringer samples was shown through experimental testing and finite element analysis (FEA) modeling. The performance of PTTR was evaluated on a pristine and initial-disbond of the skin–stringer specimen. A macro-scale pin–spring modeling approach was employed in FEA using a non-linear spring to capture the pin failure under the mixed-mode load. The experimental results showed a 15.5% and 20.9% increase in strength for the pristine-PTTR and initial-disbond PTTR specimens, respectively. The modeling approach accurately represents the overall structural response of PTTR laminate, including stiffness, adhesive strength, crack extension scenarios and progressive pin failure modes. This modeling approach can be beneficial for designing damage-tolerant structures by exploring various PTTR arrangements for achieving improved structural responses. [ABSTRACT FROM AUTHOR]

Published
2024
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138. 'There was nothing, just absolute darkness': Understanding the needs of those caring for children and young people with complex neurodisability in a diverse UK context: A qualitative exploration in the ENCOMPASS study.

Author

Prest, Kirsten, Wilson, Emma, Vassiliadou, Io, Ali, Sayeeda, Lakhanpaul, Monica, Morris, Christopher, Tann, Cally, Harniess, Phillip, Lewis‐Jackson, Sasha, Kuper, Hannah, and Heys, Michelle

Subjects
FAMILIES & psychology, HOLISTIC medicine, HEALTH services accessibility, COMMUNITY health services, PATIENTS' families, MEDICAL personnel, HUMAN services programs, QUALITATIVE research, RESEARCH funding, PEDIATRICIANS, CHILD health services, INTERVIEWING, PSYCHOLOGICAL adaptation, CEREBRAL palsy, NEUROLOGICAL disorders, PATIENT-centered care, THEMATIC analysis, RESEARCH methodology, COMMUNICATION, PARENTS of children with disabilities, PSYCHOLOGY of caregivers, NEEDS assessment, SOCIAL support, PSYCHOSOCIAL factors, CHILDREN
Abstract

Background: Children and young people (CYP) with complex neurodisability experience multiple physical, communication, educational and social challenges, which require complex packages of multidisciplinary care. Part of the holistic care required includes supporting the families and parents/caregivers. The aim of the wider study was to introduce a new programme ('Ubuntu') to parents/caregivers and healthcare professionals (HCPs) in order to test the feasibility and acceptability of the concept and content, with the goal of potential adaptation for the UK in mind. Data collection and analysis uncovered rich data on caregiving journeys, navigation of health services, and perceived service gaps. This paper focuses solely on these topics. Further papers will report on the feasibility and adaptation data. Methods: Two rounds of semi‐structured interviews were conducted with 12 caregivers of CYP with complex neurodisability and six HCPs from a variety of disciplines, recruited from a community child health service in London Borough of Newham, UK in 2020. The interviews included open‐ended questions to explore caregiving journeys, experiences of navigating health services and perceived service gaps. Transcripts were analysed using a data‐driven inductive thematic analysis. Results: Three themes were identified that related to the aim of understanding caregivers' experiences and unmet needs relating to current service provision. These were (1) Caregiver Mental Health, (2) The Information Gap and (3) The Need for Holistic Support. Mental health difficulties were reported, particularly around the period of diagnosis. Priority needs included the provision of clear information about the diagnosis and services offered, opportunities to forge peer support networks and for services across the community to collaborate. Conclusions: The delivery of health services for CYP with neurodisability should encompass the broad needs of the family as well as meeting the clinical needs of the CYP. [ABSTRACT FROM AUTHOR]

Published
2024
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140. Output-sensitive Complexity of Multiobjective Combinatorial Optimization

Author

Bökler, Fritz, Ehrgott, Matthias, Morris, Christopher, and Mutzel, Petra

Subjects
Mathematics - Optimization and Control, Computer Science - Computational Complexity, Computer Science - Data Structures and Algorithms
Abstract

We study output-sensitive algorithms and complexity for multiobjective combinatorial optimization problems. In this computational complexity framework, an algorithm for a general enumeration problem is regarded efficient if it is output-sensitive, i.e., its running time is bounded by a polynomial in the input and the output size. We provide both practical examples of MOCO problems for which such an efficient algorithm exists as well as problems for which no efficient algorithm exists under mild complexity theoretic assumptions.

Published
2016

142. Comparison of Body Composition Estimates among Norland Elite®, Lunar Idxa®, and the Bodpod® in Overweight to Obese Adults

Author

Mason, Jalyn, Morris, Christopher, Long, Douglas E., Sanden, Madison N., and Flack, Kyle

Abstract

Accurate body composition assessment, which includes fat mass (adipose tissue mass, FM), fat-free mass (FFM), and percent fat mass (%FM) is needed to evaluate health and treatment efficacy. The current study compared body composition estimates obtained from the Norland Elite® DXA, BodPod®, and iDXA® before and after a 12-week exercise intervention in adults (n=30, BMI 25-35 kg/m[superscript 2]). Bland-Altman methods determined mean bias and limits of agreement for FM, %FM, and FFM between methods. Compared to the iDXA® and BodPod®, Elite® overestimated BF% and FM (P < 0.01). FFM was similar between iDXA® and Elite® but lower in Elite® than BodPod® (P < 0.01). There were no differences between methods in changes in FM or FFM after the exercise intervention. Prior to this study, it was unknown how the Norland Elite®, a DXA model marketed to bariatric surgery patients, compared to other common body composition assessment methodologies..

Published
2020
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144. Altered ceramide metabolism is a feature in the extracellular vesicle-mediated spread of alpha-synuclein in Lewy body disorders

Author

Kurzawa-Akanbi, Marzena, Tammireddy, Seshu, Fabrik, Ivo, Gliaudelytė, Lina, Doherty, Mary K., Heap, Rachel, Matečko-Burmann, Irena, Burmann, Björn M., Trost, Matthias, Lucocq, John M., Gherman, Anda V., Fairfoul, Graham, Singh, Preeti, Burté, Florence, Green, Alison, McKeith, Ian G., Härtlova, Anetta, Whitfield, Phillip D., and Morris, Christopher M.

Published
2021
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148. Designing Muon Scattering Scanner forNuclear Debris Measurement

Author

Miyadera, Haruo, primary, Sugita, Tsukasa, additional, Fujimaki, Takuro, additional, Nakai, Yuki, additional, Noguchi, Kyohei, additional, Kusumawati, Yudhitya, additional, Yamamoto, Shuji, additional, Ueno, Souichi, additional, Kume, Naoto, additional, Kurihara, Kenji, additional, Yoda, Masaki, additional, Morris, Christopher, additional, Guardincerri, Elena, additional, Durham, Matthew, additional, and Poulson, Dan, additional

Published
2024
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149. Interventions to improve continence for children and young people with neurodisability: a national survey of practitioner and family perspectives and experiences

Author

Eke, Helen, primary, Ball, Susan, additional, Allinson, Annette, additional, Anderson, Rob, additional, Hunt, Harriet, additional, Hutton, Eve, additional, Lindsay, Claire, additional, Logan, Stuart, additional, Madden, Nicholas, additional, Melluish, Julia, additional, Richardson, Davina, additional, Rogers, June, additional, Thompson Coon, Jo, additional, Whear, Rebecca, additional, Wright, Anne, additional, and Morris, Christopher, additional

Published
2024
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