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109. Crescendo: Towards Wideband, Real-time, High-Fidelity Spectrum Sensing Systems.

Author

Subbaraman, Raghav, Mills, Kevin, Schulman, Aaron, and Bharadia, Dinesh

Subjects
SYSTEMS design, DETECTORS, PROTOTYPES, SENSES, SHARING
Abstract

Spectrum sensing systems provide real-time feedback essential for spectrum sharing. However, the growth of spectrum sharing is limited by the capabilities of these spectrum sensors. Sharing a new frequency band is only possible if sensors can detect activity in that band with sufficient time granularity and signal fidelity to meet spectrum sharing policy requirements. In this work, we introduce Crescendo, a system design that shows we can achieve wideband, real-time, high-fidelity spectrum sensing using sweeping spectrum sensors. We first provide an analysis that demonstrates there are operating points of sweeping sensors that can sense multiple popular protocols. Then we demonstrate these sensors can be built in practice with an adaptive gain super-heterodyne RF frontend with high-fidelity LO generation, and evaluate a prototype built with COTS components. In our benchmarks, Crescendo outperforms prior wideband spectrum sensors, achieving a 30 dB increase in dynamic range and 10 dB increase in SNR. [ABSTRACT FROM AUTHOR]

Published
2023
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110. Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

Author

Doykov, Ivan, Baldwin, Tomas, Spiewak, Justyna, Gilmour, Kimberly C., Gibbons, Joseph M., Pade, Corinna, Reynolds, Catherine J., McKnight, Áine, Noursadeghi, Mahdad, Maini, Mala K., Manisty, Charlotte, Treibel, Thomas, Captur, Gabriella, Fontana, Marianna, Boyton, Rosemary J., Altmann, Daniel M., Brooks, Tim, Semper, Amanda, Moon, James C., Mills, Kevin, Heywood, Wendy E., Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E., Andiapen, Mervyn, Artico, Jessica, Augusto, João B., Baca, Georgina L., Bailey, Sasha N.L., Bhuva, Anish N., Boulter, Alex, Bowles, Ruth, Bracken, Olivia V., O’Brien, Ben, Bullock, Natalie, Butler, David K., Carr, Olivia, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Coleman, Tom, Couto de Sousa, Jorge, Couto-Parada, Xose, Cross, Eleanor, Cutino-Moguel, Teresa, D’Arcangelo, Silvia, Davies, Rhodri H., Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O., Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Forooghi, Nasim, Francis, Sasha, Gillespie, David, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hemingway, Georgia, Hewson, Jacqueline, Heywood, Wendy, Hickling, Lauren M., Hicks, Bethany, Hingorani, Aroon D., Howes, Lee, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Joy, George, Kapil, Vikas, Kelly, Caoimhe, Kurdi, Hibba, Lambourne, Jonathan, Lin, Kai-Min, Liu, Siyi, Lloyd, Aaron, Louth, Sarah, Mandadapu, Vineela, Menacho, Katia, Mfuko, Celina, Millward, Sebastian, Mitchelmore, Oliver, Moon, Christopher, Moon, James, Sandoval, Diana Muñoz, Murray, Sam M., Otter, Ashley, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Mihaela, Petersen, Steffen E., Piniera, Brian, Pieper, Franziska P., Rannigan, Lisa, Rapala, Alicja, Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Rowe, Cathy, Royds, Matthew, West, Jane Sackville, Sambile, Genine, Schmidt, Nathalie M., Selman, Hannah, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D., Treibel, Thomas A., Tucker, Art, Varghese, Ann, Veerapen, Jessry, Vijayakumar, Mohit, Warner, Tim, Welch, Sophie, White, Hannah, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, Doykov, Ivan, Baldwin, Tomas, Spiewak, Justyna, Gilmour, Kimberly C., Gibbons, Joseph M., Pade, Corinna, Reynolds, Catherine J., McKnight, Áine, Noursadeghi, Mahdad, Maini, Mala K., Manisty, Charlotte, Treibel, Thomas, Captur, Gabriella, Fontana, Marianna, Boyton, Rosemary J., Altmann, Daniel M., Brooks, Tim, Semper, Amanda, Moon, James C., Mills, Kevin, Heywood, Wendy E., Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E., Andiapen, Mervyn, Artico, Jessica, Augusto, João B., Baca, Georgina L., Bailey, Sasha N.L., Bhuva, Anish N., Boulter, Alex, Bowles, Ruth, Bracken, Olivia V., O’Brien, Ben, Bullock, Natalie, Butler, David K., Carr, Olivia, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Coleman, Tom, Couto de Sousa, Jorge, Couto-Parada, Xose, Cross, Eleanor, Cutino-Moguel, Teresa, D’Arcangelo, Silvia, Davies, Rhodri H., Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O., Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Forooghi, Nasim, Francis, Sasha, Gillespie, David, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hemingway, Georgia, Hewson, Jacqueline, Heywood, Wendy, Hickling, Lauren M., Hicks, Bethany, Hingorani, Aroon D., Howes, Lee, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Joy, George, Kapil, Vikas, Kelly, Caoimhe, Kurdi, Hibba, Lambourne, Jonathan, Lin, Kai-Min, Liu, Siyi, Lloyd, Aaron, Louth, Sarah, Mandadapu, Vineela, Menacho, Katia, Mfuko, Celina, Millward, Sebastian, Mitchelmore, Oliver, Moon, Christopher, Moon, James, Sandoval, Diana Muñoz, Murray, Sam M., Otter, Ashley, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Mihaela, Petersen, Steffen E., Piniera, Brian, Pieper, Franziska P., Rannigan, Lisa, Rapala, Alicja, Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Rowe, Cathy, Royds, Matthew, West, Jane Sackville, Sambile, Genine, Schmidt, Nathalie M., Selman, Hannah, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D., Treibel, Thomas A., Tucker, Art, Varghese, Ann, Veerapen, Jessry, Vijayakumar, Mohit, Warner, Tim, Welch, Sophie, White, Hannah, Wodehouse, Theresa, Wynne, Lucinda, and Zahedi, Dan

Abstract

Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination.

Published
2022

111. Consent and the Right to Privacy

Author

Massachusetts Institute of Technology. Department of Linguistics and Philosophy, Mills, Kevin, Massachusetts Institute of Technology. Department of Linguistics and Philosophy, and Mills, Kevin

Published
2022

118. Big picture initiatives in bleeding disorders

Author

Rauch, Antoine, primary, Valentino, Leonard A., additional, Mills, Kevin, additional, Witkop, Michelle L., additional, Santaella, Maria E., additional, DiMichele, Donna, additional, Recht, Michael, additional, and Susen, Sophie, additional

Published
2022
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119. Metabolite and lipoprotein profiles reveal sex-related oxidative stress imbalance in de novo drug-naive Parkinson's disease patients

Author

Meoni, Gaia, Tenori, Leonardo, Schade, Sebastian, Licari, Cristina, Pirazzini, Chiara, Bacalini, Maria Giulia, Garagnani, Paolo, Turano, Paola, Baldelli, Luca, Jesús, Silvia, Schreglmann, Sebastian R, Sambati, Luisa, Gómez-Garre, Pilar, Halsband, Claire, Calandra-Buonaura, Giovanna, Adarmes-Gómez, Astrid Daniela, Sixel-Döring, Friederike, Zenesini, Corrado, Bhatia, Kailash P., Cortelli, Pietro, Mollenhauer, Brit, Franceschi, Claudio, Houlden, Henry, Liò, Pietro, Luchinat, Claudio, Delledonne, Massimo, Mills, Kevin, Pedersen, Nancy L., Azevedo, Tiago, Bartoletti-Stella, Anna, Bonilla-Toribio, Marta, Buiza-Rueda, Dolores, Capellari, Sabina, Carriòn-Claro, Mario, Clayton, Robert, Dal Molin, Alessandra, Dimitri, Giovanna Maria, Doykov, Ivan, Giuliani, Cristina, Hägg, Sara, Hällqvist, Jenny, Heywood, Wendy, Huertas, Ismael, Jylhävä, Juulia, Labrador-Espinosa, Miguel A., Macias, Daniel, Magrinelli, Francesca, Rodríguez, Juan Francisco Martín, Maturo, Maria Giovanna, Mengozzi, Giacomo, Milazzo, Maddalena, Nardini, Christine, Periñán-Tocino, Maria Teresa, Ravaioli, Francesco, Sala, Claudia, Spasov, Simeon, Tejera-Parrado, Cristina, Paola, Turano, Williams, Dylan, Xumerle, Luciano, Trenkwalder, Claudia, European Commission, Meoni, Gaia, Tenori, Leonardo, Schade, Sebastian, Turano, Paola, Licari, Cristina, Pirazzini, Chiara, Bacalini, Maria Giulia, Garagnani, Paolo, PROPAG-AGEING Consortium[.., Giuliani, Cristina, Provini, Federica, Calandra Buonaura, Giovanna, Cortelli, Pietro, Capellari, Sabina, ], Trenkwalder, Claudia, Franceschi, Claudio, Mollenhauer, Brit, Luchinat, Claudio, [Meoni, Gaia] Univ Florence, Magnet Resonance Ctr CERM, Florence, Italy, [Tenori, Leonardo] Univ Florence, Magnet Resonance Ctr CERM, Florence, Italy, [Licari, Cristina] Univ Florence, Magnet Resonance Ctr CERM, Florence, Italy, [Turano, Paola] Univ Florence, Magnet Resonance Ctr CERM, Florence, Italy, [Luchinat, Claudio] Univ Florence, Magnet Resonance Ctr CERM, Florence, Italy, [Meoni, Gaia] Univ Florence, Dept Chem Ugo Schiff, Florence, Italy, [Tenori, Leonardo] Univ Florence, Dept Chem Ugo Schiff, Florence, Italy, [Licari, Cristina] Univ Florence, Dept Chem Ugo Schiff, Florence, Italy, [Turano, Paola] Univ Florence, Dept Chem Ugo Schiff, Florence, Italy, [Luchinat, Claudio] Univ Florence, Dept Chem Ugo Schiff, Florence, Italy, [Tenori, Leonardo] Consorzio Interuniv Risonanze Magnet Met Prot CIR, Florence, Italy, [Turano, Paola] Consorzio Interuniv Risonanze Magnet Met Prot CIR, Florence, Italy, [Luchinat, Claudio] Consorzio Interuniv Risonanze Magnet Met Prot CIR, Florence, Italy, [Schade, Sebastian] Univ Med Ctr Goettingen, Dept Clin Neurophysiol, Gottingen, Germany, [Pirazzini, Chiara] IRCCS Ist Sci Neurol Bologna, Bologna, Italy, [Bacalini, Maria Giulia] IRCCS Ist Sci Neurol Bologna, Bologna, Italy, [Garagnani, Paolo] Univ Bologna, Dept Expt Diagnost & Specialty Med DIMES, Bologna, Italy, [Franceschi, Claudio] Univ Bologna, Dept Expt Diagnost & Specialty Med DIMES, Bologna, Italy, [Trenkwalder, Claudia] Univ Med Ctr Goettingen, Dept Neurol & Paracelsus Elena Klin, Kassel, Germany, [Mollenhauer, Brit] Univ Med Ctr Goettingen, Dept Neurol & Paracelsus Elena Klin, Kassel, Germany, [Franceschi, Claudio] Lobachevsky Univ, Lab Syst Med Hlth Aging, Nizhnii Novgorod, Russia, [Franceschi, Claudio] Lobachevsky Univ, Dept Appl Math, Nizhnii Novgorod, Russia, Instruct-ERIC, a Landmark ESFRI project, CERM/CIRMMP Italy Centre, Horizon 2020 Framework Programme (PROPAG-AGEING), Meoni, Gaia [0000-0002-8608-4641], Tenori, Leonardo [0000-0001-6438-059X], Schade, Sebastian [0000-0002-6316-6804], Turano, Paola [0000-0002-7683-8614], Franceschi, Claudio [0000-0001-9841-6386], Luchinat, Claudio [0000-0003-2271-8921], and Apollo - University of Cambridge Repository

Subjects
Risk, Metabolites, ipoproteins, sex-related, oxidative stress imbalance, Parkinson’s disease, NMR, Parkinson's disease, Serum-cholesterol, Predictive markers, Levodopa, Cellular and Molecular Neuroscience, Plasma, RC346-429, Homocysteine, Cholesterol levels, PROPAG-AGEING Consortium, Diagnostic markers, metabolomics, Nmr, Phenotypes, Neurology, PD, Neurology. Diseases of the nervous system, Neurology (clinical), Biomarkers
Abstract

Parkinson's disease (PD) is the neurological disorder showing the greatest rise in prevalence from 1990 to 2016. Despite clinical definition criteria and a tremendous effort to develop objective biomarkers, precise diagnosis of PD is still unavailable at early stage. In recent years, an increasing number of studies have used omic methods to unveil the molecular basis of PD, providing a detailed characterization of potentially pathological alterations in various biological specimens. Metabolomics could provide useful insights to deepen our knowledge of PD aetiopathogenesis, to identify signatures that distinguish groups of patients and uncover responsive biomarkers of PD that may be significant in early detection and in tracking the disease progression and drug treatment efficacy. The present work is the first large metabolomic study based on nuclear magnetic resonance (NMR) with an independent validation cohort aiming at the serum characterization of de novo drug-naive PD patients. Here, NMR is applied to sera from large training and independent validation cohorts of German subjects. Multivariate and univariate approaches are used to infer metabolic differences that characterize the metabolite and the lipoprotein profiles of newly diagnosed de novo drug-naive PD patients also in relation to the biological sex of the subjects in the study, evidencing a more pronounced fingerprint of the pathology in male patients. The presence of a validation cohort allowed us to confirm altered levels of acetone and cholesterol in male PD patients. By comparing the metabolites and lipoproteins levels among de novo drug-naive PD patients, age- and sex-matched healthy controls, and a group of advanced PD patients, we detected several descriptors of stronger oxidative stress., This work was supported by the Horizon 2020 Framework Programme (grant number 634821, PROPAG-AGEING).

Published
2022

120. Additional file 3 of Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s

Author

Toomey, Christina E., Heywood, Wendy E., Evans, James R., Lachica, Joanne, Pressey, Sarah N., Foti, Sandrine C., Al Shahrani, Mesfer, D’Sa, Karishma, Hargreaves, Iain P., Heales, Simon, Orford, Michael, Troakes, Claire, Attems, Johannes, Gelpi, Ellen, Palkovits, Miklos, Lashley, Tammaryn, Gentleman, Steve M., Revesz, Tamas, Mills, Kevin, and Gandhi, Sonia

Abstract

Additional file 3: Figure S3. Citrate synthase protein levels across the brain. Graph highlighting how much citrate synthase protein was detected per disease group and brain region. Two-way ANOVA with Sidak’s multiple comparisons determined that citrate synthase levels across disease groups were non-significant (p = 0.1647) whilst those between regions were significant (p < 0.0001). Figure and analysis made with GraphPad Prism 9.02.

Published
2022
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121. Mitochondrial dysfunction is a key pathological driver of early stage Parkinson's

Author

Toomey, Christina E, Heywood, Wendy E, Evans, James R, Lachica, Joanne, Pressey, Sarah N, Foti, Sandrine C, Al Shahrani, Mesfer, D'Sa, Karishma, Hargreaves, Iain P, Heales, Simon, Orford, Michael, Troakes, Claire, Attems, Johannes, Gelpi, Ellen, Palkovits, Miklos, Lashley, Tammaryn, Gentleman, Steve M, Revesz, Tamas, Mills, Kevin, and Gandhi, Sonia

Subjects
FOS: Clinical medicine, Stem Cells, Neurosciences, Cell Biology
Abstract

BACKGROUND: The molecular drivers of early sporadic Parkinson's disease (PD) remain unclear, and the presence of widespread end stage pathology in late disease masks the distinction between primary or causal disease-specific events and late secondary consequences in stressed or dying cells. However, early and mid-stage Parkinson's brains (Braak stages 3 and 4) exhibit alpha-synuclein inclusions and neuronal loss along a regional gradient of severity, from unaffected-mild-moderate-severe. Here, we exploited this spatial pathological gradient to investigate the molecular drivers of sporadic PD. METHODS: We combined high precision tissue sampling with unbiased large-scale profiling of protein expression across 9 brain regions in Braak stage 3 and 4 PD brains, and controls, and verified these results using targeted proteomic and functional analyses. RESULTS: We demonstrate that the spatio-temporal pathology gradient in early-mid PD brains is mirrored by a biochemical gradient of a changing proteome. Importantly, we identify two key events that occur early in the disease, prior to the occurrence of alpha-synuclein inclusions and neuronal loss: (i) a metabolic switch in the utilisation of energy substrates and energy production in the brain, and (ii) perturbation of the mitochondrial redox state. These changes may contribute to the regional vulnerability of developing alpha-synuclein pathology. Later in the disease, mitochondrial function is affected more severely, whilst mitochondrial metabolism, fatty acid oxidation, and mitochondrial respiration are affected across all brain regions. CONCLUSIONS: Our study provides an in-depth regional profile of the proteome at different stages of PD, and highlights that mitochondrial dysfunction is detectable prior to neuronal loss, and alpha-synuclein fibril deposition, suggesting that mitochondrial dysfunction is one of the key drivers of early disease.

Published
2022
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122. Additional file 2 of Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s

Author

Toomey, Christina E., Heywood, Wendy E., Evans, James R., Lachica, Joanne, Pressey, Sarah N., Foti, Sandrine C., Al Shahrani, Mesfer, D’Sa, Karishma, Hargreaves, Iain P., Heales, Simon, Orford, Michael, Troakes, Claire, Attems, Johannes, Gelpi, Ellen, Palkovits, Miklos, Lashley, Tammaryn, Gentleman, Steve M., Revesz, Tamas, Mills, Kevin, and Gandhi, Sonia

Abstract

Additional file 2: Figure S2. Candidates for validation workflow A pie chart showing the proportion of mitochondrial proteins out of the total proteins that were detected. The box outlines the method used to select candidate proteins for validation. The final pie chart shows the proportion of mitochondrial proteins within the list of proteins that were selected for validation.

Published
2022
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123. Additional file 1 of Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s

Author

Toomey, Christina E., Heywood, Wendy E., Evans, James R., Lachica, Joanne, Pressey, Sarah N., Foti, Sandrine C., Al Shahrani, Mesfer, D’Sa, Karishma, Hargreaves, Iain P., Heales, Simon, Orford, Michael, Troakes, Claire, Attems, Johannes, Gelpi, Ellen, Palkovits, Miklos, Lashley, Tammaryn, Gentleman, Steve M., Revesz, Tamas, Mills, Kevin, and Gandhi, Sonia

Abstract

Additional file 1: Figure S1. GO terms altered in early PD compared to controls and mitochondrial gene expression patterns (a) Bar charts indicating number of Gene Ontology (GO) terms that are represented in the dataset for each region as determined by Webgestalt and DAVID databases. Top chart shows Biological processes, middle the molecular functions and lower the cellular components. The pie chart adjacent to each chart shows the number of GO terms that overlap or are uniquely represented in the dataset for a region of severe pathology (substantia nigra), mild pathology (parahippocampus) and a region unaffected at Braak stage 3/4 (frontal cortex) as determined by GOview. Colours indicate the level each region is affected at Braak stage 3/4 as determined in Figure 1b. Protein heatmaps from (b) first mass spectrometry run and (c) second mass spectrometry run from IPA showing the level of expression change per protein in the Mitochondrial Dysfunction pathway across each brain region in Braak stage 3/4 compared to controls. Red indicated upregulation and green indicated downregulation compared to controls. Intensity of colour shows level of expression change with deeper colour indicating higher up- or down- regulation.

Published
2022
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128. Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

Author

Doykov, Ivan, primary, Spiewak, Justyna, additional, Gilmour, Kimberly C., additional, Gibbons, Joseph M, additional, Pade, Corinna, additional, McKnight, Áine, additional, Noursadeghi, Mahdad, additional, Maini, Mala K, additional, Manisty, Charlotte, additional, Treibel, Thomas, additional, Captur, Gabriella, additional, Fontana, Marianna, additional, Boyton, Rosemary J, additional, Altmann, Daniel M, additional, Brooks, Tim, additional, Semper, Amanda, additional, Moon, James C, additional, Mills, Kevin, additional, and Heywood, Wendy, additional

Published
2022
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129. Tissue Proteome of 2-Hydroxyacyl-CoA Lyase Deficient Mice Reveals Peroxisome Proliferation and Activation of ω-Oxidation

Author

Khalil, Youssef, primary, Carrino, Sara, additional, Lin, Fujun, additional, Ferlin, Anna, additional, Lad, Heena V., additional, Mazzacuva, Francesca, additional, Falcone, Sara, additional, Rivers, Natalie, additional, Banks, Gareth, additional, Concas, Danilo, additional, Aguilar, Carlos, additional, Haynes, Andrew R., additional, Blease, Andy, additional, Nicol, Thomas, additional, Al-Shawi, Raya, additional, Heywood, Wendy, additional, Potter, Paul, additional, Mills, Kevin, additional, Gale, Daniel P., additional, and Clayton, Peter T., additional

Published
2022
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130. Cerebrospinal fluid neurofilament light chain levels in CLN2 disease patients treated with enzyme replacement therapy normalise after two years on treatment

Author

Iwan, Katharina, primary, Patel, Nina, additional, Heslegrave, Amanda, additional, Borisova, Mina, additional, Lee, Laura, additional, Bower, Rebecca, additional, Mole, Sara E., additional, Mills, Philippa B., additional, Zetterberg, Henrik, additional, Mills, Kevin, additional, Gissen, Paul, additional, and Heywood, Wendy E., additional

Published
2022
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133. Heterogeneity of prodromal Parkinson symptoms in siblings of Parkinson disease patients

Author

Baldelli, Luca, Schade, Sebastian, Jesús, Silvia, Schreglmann, Sebastian R., Sambati, Luisa, Gómez-Garre, Pilar, Halsband, Claire, Calandra-Buonaura, Giovanna, Adarmes-Gómez, Astrid Daniela, Sixel-Döring, Friederike, Zenesini, Corrado, Pirazzini, Chiara, Garagnani, Paolo, Bacalini, Maria Giulia, Bhatia, Kailash P., Cortelli, Pietro, Mollenhauer, Brit, Franceschi, Claudio, Mir, Pablo, Trenkwalder, Claudia, Provini, Federica, Houlden, Henry, Liò, Pietro, Luchinat, Claudio, Delledonne, Massimo, Mills, Kevin, Pedersen, Nancy L., Azevedo, Tiago, Bartoletti-Stella, Anna, Bonilla-Toribio, Marta, Buiza-Rueda, Dolores, Capellari, Sabina, Carriòn-Claro, Mario, Clayton, Robert, Dal Molin, Alessandra, Dimitri, Giovanna Maria, Doykov, Ivan, Giuliani, Cristina, Hägg, Sara, Hällqvist, Jenny, Heywood, Wendy, Huertas, Ismael, Jylhävä, Juulia, Labrador-Espinosa, Miguel A., Licari, Cristina, Macias, Daniel, Magrinelli, Francesca, Rodríguez, Juan Francisco Martín, Maturo, Maria Giovanna, Mengozzi, Giacomo, Meoni, Gaia, Milazzo, Maddalena, Nardini, Christine, Periñán-Tocino, Maria Teresa, Ravaioli, Francesco, Sala, Claudia, Spasov, Simeon, Tejera-Parrado, Cristina, Tenori, Leonardo, Paola, Turano, Williams, Dylan, Xumerle, Luciano, Zago, Elisa, Broli, Marcella, De Massis, Patrizia, Escuela-Martin, Rocio, Fabbri, Giovanni, Gabellini, Anna, Guaraldi, Pietro, Macrì, Stefania, Nassetti, Stefania Alessandra, Scaglione, Cesa Lorella Maria, Valzania, Franco, Rosaria, Cilea, Mignani, Francesco, Ortega, Rosario Vigo, Boninsegna, Claudia, De Luca, Silvia, Schade, Sebastian [0000-0002-6316-6804], Gómez-Garre, Pilar [0000-0002-0437-6182], Mir, Pablo [0000-0003-1656-302X], Provini, Federica [0000-0001-9063-2658], and Apollo - University of Cambridge Repository

Subjects
692/617/375/1718, 692/53/2423, article, 692/499
Abstract

A prodromal phase of Parkinson’s disease (PD) may precede motor manifestations by decades. PD patients’ siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort. 340 PD siblings from three sites (Bologna, Seville, Kassel/Goettingen) underwent clinical and neurological evaluations of PD markers. The German part of the cohort was compared with German de novo PD patients (dnPDs) and healthy controls (CTRs) from DeNoPa. Fifteen (4.4%) siblings presented with subtle signs of motor impairment, with MDS-UPDRS-III scores not clinically different from CTRs. Symptoms of orthostatic hypotension were present in 47 siblings (13.8%), no different to CTRs (p = 0.072). No differences were found for olfaction and overall cognition; German-siblings performed worse than CTRs in visuospatial-executive and language tasks. 3/147 siblings had video-polysomnography-confirmed REM sleep behavior disorder (RBD), none was positive on the RBD Screening Questionnaire. 173/300 siblings had

Published
2021

135. Island treasures: rapid assessment of orchids on Norfolk Island.

Author

Zimmer, Heidi, Christian, Joel, Christian, Naomi, Clements, Mark, Nance, Alexandra, Nargar, Katharina, Macgregor, Nicholas A., Mills, Kevin, and Wilson, Mel

Subjects
ORCHIDS, ENDEMIC species, BIODIVERSITY conservation, TAXONOMY
Abstract

Islands, because of their small geographic area and tendency for high levels of species endemism, present opportunities for comprehensive biodiversity assessment and conservation. Norfolk Island (35 km² in area) is in the South Pacific Ocean, between New Zealand and New Caledonia, approximately 1500 km east of Australia. To assess the conservation and taxonomic status of the orchids of Norfolk Island we analysed historical literature and herbarium records, and then conducted a 10-day field survey. We made 91 records of 11 orchid species, including the first record of Pinalia rostriflora (Rchb.f.) Kuntze for the island. The orchid flora of Norfolk Island is relatively species rich, compared to other small oceanic islands. Because of Norfolk Island's small land area, its endemic orchids may be eligible for listing as Critically Endangered under Australian Government legislation (the Environment Protection and Biodiversity Conservation Act 1999), due to their restricted geographic range. Targeted assessments, such as this, raise awareness of the presence and distribution of threatened species, and give confidence to land managers in prioritising conservation management actions. [ABSTRACT FROM AUTHOR]

Published
2023
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136. Niemann-Pick type C disease as proof-of-concept for intelligent biomarker panel selection in neurometabolic disorders.

Author

Papandreou, Apostolos, Doykov, Ivan, Spiewak, Justyna, Komarov, Nikita, Habermann, Stephanie, Kurian, Manju A., Mills, Philippa B., Mills, Kevin, Gissen, Paul, Heywood, Wendy E., and Clinical cohort recruitment and characterization group

Abstract

Aim: Using Niemann-Pick type C disease (NPC) as a paradigm, we aimed to improve biomarker discovery in patients with neurometabolic disorders.Method: Using a multiplexed liquid chromatography tandem mass spectrometry dried bloodspot assay, we developed a selective intelligent biomarker panel to monitor known biomarkers N-palmitoyl-O-phosphocholineserine and 3β,5α,6β-trihydroxy-cholanoyl-glycine as well as compounds predicted to be affected in NPC pathology. We applied this panel to a clinically relevant paediatric patient cohort (n = 75; 35 males, 40 females; mean age 7 years 6 months, range 4 days-19 years 8 months) presenting with neurodevelopmental and/or neurodegenerative pathology, similar to that observed in NPC.Results: The panel had a far superior performance compared with individual biomarkers. Namely, NPC-related established biomarkers used individually had 91% to 97% specificity but the combined panel had 100% specificity. Moreover, multivariate analysis revealed long-chain isoforms of glucosylceramide were elevated and very specific for patients with NPC.Interpretation: Despite advancements in next-generation sequencing and precision medicine, neurological non-enzymatic disorders remain difficult to diagnose and lack robust biomarkers or routine functional testing for genetic variants of unknown significance. Biomarker panels may have better diagnostic accuracy than individual biomarkers in neurometabolic disorders, hence they can facilitate more prompt disease identification and implementation of emerging targeted, disease-specific therapies.What This Paper Adds: Intelligent biomarker panel design can help expedite diagnosis in neurometabolic disorders. In Niemann-Pick type C disease, such a panel performed better than individual biomarkers. Biomarker panels are easy to implement and widely applicable to neurometabolic conditions. [ABSTRACT FROM AUTHOR]

Published
2022
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145. Government Open Systems Interconnection: Profile in Progress.

Author

Mills, Kevin L.

Abstract

Describes the emergence of Open Systems Interconnection (OSI) as it relates to the U.S. Government Open Systems Interconnection Profile (GOSIP); defines GOSIP; and speculates about its future. Challenges facing GOSIP that are related to test policies and procedures, strategic and tactical planning, additional functionality, and international cooperation are identified. (nine references) (SD)

Published
1990

147. Cerebrospinal fluid neurofilament light levels in CLN2 disease patients treated with enzyme replacement therapy normalise after two years on treatment

Author

Iwan, Katharina, primary, Patel, Nina, additional, Heslegrave, Amanda, additional, Borisova, Mina, additional, Lee, Laura, additional, Bower, Rebecca, additional, Mole, Sara E., additional, Mills, Philippa B., additional, Zetterberg, Henrik, additional, Mills, Kevin, additional, Gissen, Paul, additional, and Heywood, Wendy E., additional

Published
2021
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148. Association of measures of body fat with serum alpha-tocopherol and its metabolites in middle-aged individuals

Author

Meulmeester, Fleur L., primary, Luo, Jiao, additional, Martens, Leon G., additional, Ashrafi, Nadia, additional, de Mutsert, Renée, additional, Mook-Kanamori, Dennis O., additional, Lamb, Hildo J., additional, Rosendaal, Frits R., additional, Willems van Dijk, Ko, additional, Mills, Kevin, additional, van Heemst, Diana, additional, and Noordam, Raymond, additional

Published
2021
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149. Urinary oxidized, but not enzymatic vitamin E metabolites are inversely associated with measures of glucose homeostasis in middle-aged healthy individuals

Author

Luo, Jiao, primary, Meulmeester, Fleur L., additional, Martens, Leon G., additional, Ashrafi, Nadia, additional, de Mutsert, Renée, additional, Mook-Kanamori, Dennis O., additional, Rosendaal, Frits R., additional, Willems van Dijk, Ko, additional, le Cessie, Saskia, additional, Mills, Kevin, additional, Noordam, Raymond, additional, and van Heemst, Diana, additional

Published
2021
Full Text
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