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121 results on '"Beekman, M."'

2. Wafer-scale uniformity of Dolan-bridge and bridgeless Manhattan-style Josephson junctions for superconducting quantum processors

Author

Muthusubramanian, N., Duivestein, P., Zachariadis, C., Finkel, M., van der Meer, S. L. M., Veen, H. M., Beekman, M. W., Stavenga, T., Bruno, A., and DiCarlo, L.

Subjects
Quantum Physics, Condensed Matter - Superconductivity
Abstract

We investigate die-level and wafer-scale uniformity of Dolan-bridge and bridgeless Manhattan Josephson junctions, using multiple substrates with and without through-silicon vias (TSVs). Dolan junctions fabricated on planar substrates have the highest yield and lowest room-temperature conductance spread, equivalent to ~100 MHz in transmon frequency. In TSV-integrated substrates, Dolan junctions suffer most in both yield and disorder, making Manhattan junctions preferable. Manhattan junctions show pronounced conductance decrease from wafer centre to edge, which we qualitatively capture using a geometric model of spatially-dependent resist shadowing during junction electrode evaporation. Analysis of actual junction overlap areas using scanning electron micrographs supports the model, and further points to a remnant spatial dependence possibly due to contact resistance., Comment: 25 pages, 13 figures, 1 table

Published
2023

3. Post-fabrication frequency trimming of coplanar-waveguide resonators in circuit QED quantum processors

Author

Vallés-Sanclemente, S., van der Meer, S. L. M., Finkel, M., Muthusubramanian, N., Beekman, M., Ali, H., Marques, J. F., Zachariadis, C., Veen, H. M., Stavenga, T., Haider, N., and DiCarlo, L.

Subjects
Quantum Physics, Condensed Matter - Superconductivity
Abstract

We present the use of grounding airbridge arrays to trim the frequency of microwave coplanar-waveguide (CPW) resonators post fabrication. This method is compatible with the fabrication steps of conventional CPW airbridges and crossovers and increases device yield by allowing compensation of design and fabrication uncertainty with $100~\mathrm{MHz}$ range and $10~\mathrm{MHz}$ resolution. We showcase two applications in circuit QED. The first is elimination of frequency crowding between resonators intended to readout different transmons by frequency-division multiplexing. The second is frequency matching of readout and Purcell-filter resonator pairs. Combining this matching with transmon frequency trimming by laser annealing reliably achieves fast and high-fidelity readout across 17-transmon quantum processors., Comment: 8 pages and 6 figures

Published
2023
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4. All-microwave leakage reduction units for quantum error correction with superconducting transmon qubits

Author

Marques, J. F., Ali, H., Varbanov, B. M., Finkel, M., Veen, H. M., van der Meer, S. L. M., Valles-Sanclemente, S., Muthusubramanian, N., Beekman, M., Haider, N., Terhal, B. M., and DiCarlo, L.

Subjects
Quantum Physics, Condensed Matter - Superconductivity
Abstract

Minimizing leakage from computational states is a challenge when using many-level systems like superconducting quantum circuits as qubits. We realize and extend the quantum-hardware-efficient, all-microwave leakage reduction unit (LRU) for transmons in a circuit QED architecture proposed by Battistel et al. This LRU effectively reduces leakage in the second- and third-excited transmon states with up to $99\% $ efficacy in $220~\mathrm{ns}$, with minimum impact on the qubit subspace. As a first application in the context of quantum error correction, we demonstrate the ability of multiple simultaneous LRUs to reduce the error detection rate and to suppress leakage buildup within $1\%$ in data and ancilla qubits over 50 cycles of a weight-2 parity measurement., Comment: 11 pages, 11 figures, 1 table; typos corrected

Published
2023
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5. Realization of a quantum neural network using repeat-until-success circuits in a superconducting quantum processor

Author

Moreira, M. S., Guerreschi, G. G., Vlothuizen, W., Marques, J. F., van Straten, J., Premaratne, S. P., Zou, X., Ali, H., Muthusubramanian, N., Zachariadis, C., van Someren, J., Beekman, M., Haider, N., Bruno, A., Almudever, C. G., Matsuura, A. Y., and DiCarlo, L.

Subjects
Quantum Physics
Abstract

Artificial neural networks are becoming an integral part of digital solutions to complex problems. However, employing neural networks on quantum processors faces challenges related to the implementation of non-linear functions using quantum circuits. In this paper, we use repeat-until-success circuits enabled by real-time control-flow feedback to realize quantum neurons with non-linear activation functions. These neurons constitute elementary building blocks that can be arranged in a variety of layouts to carry out deep learning tasks quantum coherently. As an example, we construct a minimal feedforward quantum neural network capable of learning all 2-to-1-bit Boolean functions by optimization of network activation parameters within the supervised-learning paradigm. This model is shown to perform non-linear classification and effectively learns from multiple copies of a single training state consisting of the maximal superposition of all inputs., Comment: 24 pages, 22 figures, 3 tables

Published
2022

7. NMR metabolomics-guided DNA methylation mortality predictors

Author

Geleijnse, J.M., Boersma, E., van Spil, W.E., van Greevenbroek, M.M.J., Stehouwer, C.D.A., van der Kallen, C.J.H., Arts, I.C.W., Rutters, F., Beulens, J.W.J., Muilwijk, M., Elders, P.J.M., 't Hart, L.M., Ghanbari, M., Ikram, M.A., Netea, M.G., Kloppenburg, M., Ramos, Y.F.M., Bomer, N., Meulenbelt, I., Stronks, K., Snijder, M.B., Zwinderman, A.H., Heijmans, B.T., Lumey, L.H., Wijmenga, C., Fu, J., Zhernakova, A., Deelen, J., Mooijaart, S.P., Beekman, M., Slagboom, P.E., Onderwater, G.L.J., van den Maagdenberg, A.M.J.M., Terwindt, G.M., Thesing, C., Bot, M., Penninx, B.W.J.H., Trompet, S., Jukema, J.W., Sattar, N., van der Horst, I.C.C., van der Harst, P., So-Osman, C., van Hilten, J.A., Nelissen, R.G.H.H., Höfer, I.E., Asselbergs, F.W., Scheltens, P., Teunissen, C.E., van der Flier, W.M., van Dongen, J., Pool, R., Willemsen, A.H.M., Boomsma, D.I., Suchiman, H.E.D., Barkey Wolf, J.J.H., Cats, D., Mei, H., Slofstra, M., Swertz, M., Reinders, M.J.T., van den Akker, E.B., Bizzarri, Daniele, Reinders, Marcel J.T., Kuiper, Lieke, Beekman, Marian, Deelen, Joris, van Meurs, Joyce B.J., van Dongen, Jenny, Pool, René, Boomsma, Dorret I., Ghanbari, Mohsen, Franke, Lude, Slagboom, Pieternella E., and van den Akker, Erik B.

Published
2024
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12. A Cross-Sectional Study on Prescription Patterns of Short-Acting β2-Agonists in Patients with Asthma: Results from the SABINA III Colombia Cohort

Author

Pedrozo-Pupo JC, Pacheco Gallego MC, Baños Álvarez IDJ, Jaller Raad RA, Caballero Pinilla AC, Reynales Londoño H, Bernal Villada L, and Beekman M

Subjects
exacerbations, inhaled corticosteroids, over-prescription, practice patterns, prescriptions, Immunologic diseases. Allergy, RC581-607
Abstract

John Carlos Pedrozo-Pupo,1 Manuel Conrado Pacheco Gallego,2 Iván de Jesús Baños Álvarez,3 Rodolfo Antonio Jaller Raad,4 Andrea Carolina Caballero Pinilla,5 Humberto Reynales Londoño,6 Laura Bernal Villada,7 Maarten Beekman8 1PREVICARE LTDA. Programa de Medicina, Facultad de Ciencias de la Salud, Universidad del Magdalena, Santa Marta, Colombia; 2División de Neumología y Endoscopia Respiratoria, Departamento de Medicina Interna, Universidad Tecnológica de Pereira, Universidad Visión de las Américas, RESPIREMOS Centro de Neumología y Endoscopia Respiratoria, Pereira, Colombia; 3Centro de Rehabilitación Pulmonar Integral S.A.S., Cartagena, Colombia; 4Department of Allergy and Immunology, Centro de Investigación Médico Asistencial S.A.S, Barranquilla, Colombia; 5Centro de Investigación Clínica, Caja de Compensación Familiar CAFAM, Sede Centro de Atención en Salud CAFAM Floresta, Bogotá, Colombia; 6Clinical Research Department, Centro de Atención e Investigación Médica - CAIMED, Chía, Colombia; 7Andean Cluster - Respiratory & Immunology, AstraZeneca, Bogotá, Colombia; 8Respiratory & Immunology AstraZeneca, The Hague, the NetherlandsCorrespondence: John Carlos Pedrozo-Pupo, PREVICARE LTDA. Programa de Medicina, Facultad de Ciencias de la Salud, Universidad del Magdalena, Santa Marta, Colombia, Tel +57 603017384712, Email jhonpedrozo@hotmail.comPurpose: Overuse of short-acting β2-agonists (SABAs) for asthma is associated with a significant increase in exacerbations and healthcare resource use. However, limited data exist on the extent of SABA overuse outside of Europe and North America. As part of the multi-country SABA use IN Asthma (SABINA) III study, we characterized SABA prescription patterns in Colombia.Patients and Methods: This observational, cross-sectional cohort study of SABINA III included patients (aged ≥ 12 years) with asthma recruited from seven sites in Colombia. Demographics, disease characteristics (including investigator-defined asthma severity guided by the 2017 Global Initiative for Asthma report), and asthma treatments prescribed (including SABAs and inhaled corticosteroids [ICS]) in the 12 months preceding the study were recorded using electronic case report forms during a single study visit.Results: Of 250 patients analyzed, 50.4%, 33.2%, and 16.4% were enrolled by pulmonologists, general medicine practitioners, and allergists, respectively. Most patients were female (74.0%) and had moderate-to-severe asthma (67.6%). Asthma was partly controlled or uncontrolled in 57.6% of patients, with 15.6% experiencing ≥ 1 severe exacerbation 12 months before the study visit. In total, 4.0% of patients were prescribed SABA monotherapy and 55.6%, SABA in addition to maintenance therapy. Overall, 39.2% of patients were prescribed ≥ 3 SABA canisters in the 12 months before the study visit; 25.2% were prescribed ≥ 10 canisters. Additionally, 17.6% of patients purchased SABAs over the counter, of whom 43.2% purchased ≥ 3 canisters. Maintenance medication in the form of ICS or ICS/long-acting β2-agonist fixed-dose combination was prescribed to 36.0% and 66.8% of patients, respectively.Conclusion: Our findings suggest that prescription/purchase of ≥ 3 SABA canisters were common in Colombia, highlighting a public health concern. There is a need to improve asthma care by aligning clinical practices with the latest evidence-based treatment recommendations to improve asthma management across Colombia.Keywords: exacerbations, inhaled corticosteroids, over-prescription, practice patterns, prescriptions

Published
2022

16. NMR metabolomics-guided DNA methylation mortality predictors

Author

Bizzarri, Daniele, Reinders, Marcel J.T., Kuiper, Lieke, Beekman, Marian, Deelen, Joris, van Meurs, Joyce B.J., van Dongen, Jenny, Pool, René, Boomsma, D. I., Ghanbari, M., Franke, Lude, Geleijnse, J. M., Boersma, E., van Spil, W. E., van Greevenbroek, M. M.J., Stehouwer, C. D.A., van der Kallen, C. J.H., Arts, I. C.W., Rutters, F., Beulens, J. W.J., Muilwijk, M., Elders, P. J.M., 't Hart, L. M., Ikram, M. A., Netea, M. G., Kloppenburg, M., Ramos, Y. F.M., Bomer, N., Meulenbelt, I., Stronks, K., Snijder, M. B., Zwinderman, A. H., Heijmans, B. T., Lumey, L. H., Fu, J., Deelen, J., Mooijaart, S. P., Beekman, M., Bot, M., Trompet, S., van der Horst, I. C.C., So-Osman, C., Nelissen, R. G.H.H., Teunissen, C. E., van Dongen, J., Willemsen, A. H.M., Mei, H., Reinders, M. J.T., van den Akker, E. B., Bizzarri, Daniele, Reinders, Marcel J.T., Kuiper, Lieke, Beekman, Marian, Deelen, Joris, van Meurs, Joyce B.J., van Dongen, Jenny, Pool, René, Boomsma, D. I., Ghanbari, M., Franke, Lude, Geleijnse, J. M., Boersma, E., van Spil, W. E., van Greevenbroek, M. M.J., Stehouwer, C. D.A., van der Kallen, C. J.H., Arts, I. C.W., Rutters, F., Beulens, J. W.J., Muilwijk, M., Elders, P. J.M., 't Hart, L. M., Ikram, M. A., Netea, M. G., Kloppenburg, M., Ramos, Y. F.M., Bomer, N., Meulenbelt, I., Stronks, K., Snijder, M. B., Zwinderman, A. H., Heijmans, B. T., Lumey, L. H., Fu, J., Deelen, J., Mooijaart, S. P., Beekman, M., Bot, M., Trompet, S., van der Horst, I. C.C., So-Osman, C., Nelissen, R. G.H.H., Teunissen, C. E., van Dongen, J., Willemsen, A. H.M., Mei, H., Reinders, M. J.T., and van den Akker, E. B.

Abstract

Background: 1H-NMR metabolomics and DNA methylation in blood are widely known biomarkers predicting age-related physiological decline and mortality yet exert mutually independent mortality and frailty signals. Methods: Leveraging multi-omics data in four Dutch population studies (N = 5238, ∼40% of which male) we investigated whether the mortality signal captured by 1H-NMR metabolomics could guide the construction of DNA methylation-based mortality predictors. Findings: We trained DNA methylation-based surrogates for 64 metabolomic analytes and found that analytes marking inflammation, fluid balance, or HDL/VLDL metabolism could be accurately reconstructed using DNA-methylation assays. Interestingly, a previously reported multi-analyte score indicating mortality risk (MetaboHealth) could also be accurately reconstructed. Sixteen of our derived surrogates, including the MetaboHealth surrogate, showed significant associations with mortality, independent of relevant covariates. Interpretation: The addition of our metabolic analyte-derived surrogates to the well-established epigenetic clock GrimAge demonstrates that our surrogates potentially represent valuable mortality signal. Funding: BBMRI-NL, X-omics, VOILA, Medical Delta, NWO, ERC.

Published
2024

17. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

Author

Sterenborg, R.B.T.M., Steinbrenner, I., Li, Yong, Bujnis, M.N., Naito, T., Marouli, E., Galesloot, T.E., Babajide, O., Andreasen, L., Astrup, A., Åsvold, B.O., Bandinelli, S., Beekman, M., Beilby, J.P., Bork-Jensen, J., Boutin, T., Brody, J.A., Brown, S.J., Brumpton, B., Campbell, P.J., Cappola, A.R., Ceresini, G., Chaker, L., Chasman, D.I., Concas, M.P., Coutinho de Almeida, Rodrigo, Cross, S.M., Cucca, F., Deary, I.J., Kjaergaard, A.D., Echouffo Tcheugui, J.B., Ellervik, C., Eriksson, J.G., Ferrucci, L., Freudenberg, J., Fuchsberger, C., Gieger, C., Giulianini, F., Gögele, M., Graham, S.E., Grarup, N., Gunjača, I., Hansen, T., Harding, B.N., Harris, S.E., Haunsø, S., Hayward, C., Hui, J., Ittermann, T., Jukema, J.W., Kajantie, E., Kanters, J.K., Kårhus, L.L., Kiemeney, L.A.L.M., Kühnel, B., Lahti, J., Langenberg, C., Lapauw, B., Leese, G., Li, Shuo, Liewald, D.C.M., Linneberg, A., Lominchar, J.V.T., Luan, Jian'an, Martin, N.G., Matana, A., Meima, M.E., Meitinger, T., Meulenbelt, I., Mitchell, B.D., Møllehave, L.T., Mora, S., Naitza, S., Nauck, M., Netea-Maier, R.T., Noordam, R., Nursyifa, C., Okada, Y., Onano, S., Papadopoulou, A., Palmer, C.N.A., Pattaro, C., Pedersen, O., Peters, A., Pietzner, M., Polašek, O., Pramstaller, P.P., Psaty, B.M., Punda, A., Ray, D., Redmond, P., Richards, J.B., Ridker, P.M., Russ, T.C., Ryan, K.A., Olesen, M.S., Schultheiss, U.T., Selvin, E., Siddiqui, M.K., Teumer, A., Medici, M., Sterenborg, R.B.T.M., Steinbrenner, I., Li, Yong, Bujnis, M.N., Naito, T., Marouli, E., Galesloot, T.E., Babajide, O., Andreasen, L., Astrup, A., Åsvold, B.O., Bandinelli, S., Beekman, M., Beilby, J.P., Bork-Jensen, J., Boutin, T., Brody, J.A., Brown, S.J., Brumpton, B., Campbell, P.J., Cappola, A.R., Ceresini, G., Chaker, L., Chasman, D.I., Concas, M.P., Coutinho de Almeida, Rodrigo, Cross, S.M., Cucca, F., Deary, I.J., Kjaergaard, A.D., Echouffo Tcheugui, J.B., Ellervik, C., Eriksson, J.G., Ferrucci, L., Freudenberg, J., Fuchsberger, C., Gieger, C., Giulianini, F., Gögele, M., Graham, S.E., Grarup, N., Gunjača, I., Hansen, T., Harding, B.N., Harris, S.E., Haunsø, S., Hayward, C., Hui, J., Ittermann, T., Jukema, J.W., Kajantie, E., Kanters, J.K., Kårhus, L.L., Kiemeney, L.A.L.M., Kühnel, B., Lahti, J., Langenberg, C., Lapauw, B., Leese, G., Li, Shuo, Liewald, D.C.M., Linneberg, A., Lominchar, J.V.T., Luan, Jian'an, Martin, N.G., Matana, A., Meima, M.E., Meitinger, T., Meulenbelt, I., Mitchell, B.D., Møllehave, L.T., Mora, S., Naitza, S., Nauck, M., Netea-Maier, R.T., Noordam, R., Nursyifa, C., Okada, Y., Onano, S., Papadopoulou, A., Palmer, C.N.A., Pattaro, C., Pedersen, O., Peters, A., Pietzner, M., Polašek, O., Pramstaller, P.P., Psaty, B.M., Punda, A., Ray, D., Redmond, P., Richards, J.B., Ridker, P.M., Russ, T.C., Ryan, K.A., Olesen, M.S., Schultheiss, U.T., Selvin, E., Siddiqui, M.K., Teumer, A., and Medici, M.

Abstract

Contains fulltext : 304858.pdf (Publisher’s version ) (Open Access), To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.

Published
2024

19. Secondary integrated analysis of multi-tissue transcriptomic responses to a combined lifestyle intervention in older adults from the GOTO nonrandomized trial.

Author

Bogaards, F. A., Gehrmann, T., Beekman, M., Lakenberg, N., Suchiman, H. E. D., de Groot, C. P. G. M., Reinders, M. J. T., and Slagboom, P. E.

Subjects
ADIPOSE tissues, OLDER people, EXTRACELLULAR matrix, TRANSCRIPTOMES, SECONDARY analysis
Abstract

Molecular effects of lifestyle interventions are typically studied in a single tissue. Here, we perform a secondary analysis on the sex-specific effects of the Growing Old TOgether trial (GOTO, trial registration number GOT NL3301 (https://onderzoekmetmensen.nl/nl/trial/27183), NL-OMON27183, primary outcomes have been previously reported in ref. 1), a moderate 13-week combined lifestyle intervention on the transcriptomes of postprandial blood, subcutaneous adipose tissue (SAT) and muscle tissue in healthy older adults, the overlap in effect between tissues and their relation to whole-body parameters of metabolic health. The GOTO intervention has virtually no effect on the postprandial blood transcriptome, while the SAT and muscle transcriptomes respond significantly. In SAT, pathways involved in HDL remodeling, O2/CO2 exchange and signaling are overrepresented, while in muscle, collagen and extracellular matrix pathways are significantly overexpressed. Additionally, we find that the effects of the SAT transcriptome closest associates with gains in metabolic health. Lastly, in males, we identify a shared variation between the transcriptomes of the three tissues. We conclude that the GOTO intervention has a significant effect on metabolic and muscle fibre pathways in the SAT and muscle transcriptome, respectively. Aligning the response in the three tissues revealed a blood transcriptome component which may act as an integrated health marker for metabolic intervention effects across tissues. Molecular effects of lifestyle interventions are typically studied within one tissue, neglecting potential shared responses across tissues. Here, the authors show that subcutaneous adipose tissue RNA levels best capture health benefits of the intervention and identified joint effects among blood, subcutaneous adipose tissue and muscle tissue RNA levels. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Over-prescription of short-acting β2-agonists for asthma in South Africa: Results from the SABINA III study

Author

Smith, C, Ambaram, A, Mitha, E, Abdullah, I, Abdullah, I A, Reddy, J, Trokis, J, Ramlachan, P, Govind, U, Lightfoot, K, Moodley, K, Smit, R, and Beekman, M J H I

Subjects
Pulmonary and Respiratory Medicine, Infectious Diseases, Asthma, exacerbations, over-prescription, SABINA, SABA, short-acting β2-agonist, South Africa, Critical Care and Intensive Care Medicine
Abstract

Background. Asthma medication prescription trends, including those of short-acting β2-agonists (SABAs), are not well documented for South Africa (SA).Objectives. To describe demographics, disease characteristics and asthma prescription patterns in the SA cohort of the SABA use IN Asthma (SABINA) III study. Methods. An observational, cross-sectional study conducted at 12 sites across SA. Patients with asthma (aged ≥12 years) were classified by investigator-defined asthma severity, guided by the Global Initiative for Asthma (GINA) 2017 recommendations, and practice type (primary/ specialist care). Data were collected using electronic case report forms.Results. Overall, 501 patients were analysed − mean (standard deviation) age, 48.4 (16.6) years; 68.3% female − of whom 70.6% and 29.4% were enrolled by primary care physicians and specialists, respectively. Most patients were classified with moderate-to-severe asthma (55.7%; GINA treatment steps 3 - 5), were overweight or obese (70.7%) and reported full healthcare reimbursement (55.5%). Asthma was partly controlled/uncontrolled in 60.3% of patients, with 46.1% experiencing ≥1 severe exacerbations in the 12 months before the study visit. Overall, 74.9% of patients were prescribed ≥3 SABA canisters in the previous 12 months (over-prescription); 56.5% were prescribed ≥10 SABA canisters. Additionally, 27.1% of patients reported purchasing SABA over-the-counter (OTC); among patients with both SABA purchase and prescriptions, 75.4% and 51.5% already received prescriptions for ≥3 and ≥10 SABA canisters, respectively, in the preceding 12 months. Conclusion. SABA over-prescription and OTC purchase were common in SA, demonstrating an urgent need to align clinical practices with the latest evidence-based recommendations and regulate SABA OTC purchase to improve asthma outcomes.

Published
2022

25. All-Microwave Leakage Reduction Units for Quantum Error Correction with Superconducting Transmon Qubits

Author

Marques, J. F., primary, Ali, H., additional, Varbanov, B. M., additional, Finkel, M., additional, Veen, H. M., additional, van der Meer, S. L. M., additional, Valles-Sanclemente, S., additional, Muthusubramanian, N., additional, Beekman, M., additional, Haider, N., additional, Terhal, B. M., additional, and DiCarlo, L., additional

Published
2023
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26. Realization of a quantum neural network using repeat-until-success circuits in a superconducting quantum processor

Author

Vlothuizen, W.J. (author), Ferreira Marques, J.M. (author), van Straten, J. (author), Ali, H. (author), Muthusubramanian, N. (author), Zachariadis, C. (author), van Someren, J. (author), Beekman, M. (author), Haider, S.N. (author), Bruno, A. (author), Almudever, Carmen G. (author), DiCarlo, L. (author), Vlothuizen, W.J. (author), Ferreira Marques, J.M. (author), van Straten, J. (author), Ali, H. (author), Muthusubramanian, N. (author), Zachariadis, C. (author), van Someren, J. (author), Beekman, M. (author), Haider, S.N. (author), Bruno, A. (author), Almudever, Carmen G. (author), and DiCarlo, L. (author)

Abstract

Artificial neural networks are becoming an integral part of digital solutions to complex problems. However, employing neural networks on quantum processors faces challenges related to the implementation of non-linear functions using quantum circuits. In this paper, we use repeat-until-success circuits enabled by real-time control-flow feedback to realize quantum neurons with non-linear activation functions. These neurons constitute elementary building blocks that can be arranged in a variety of layouts to carry out deep learning tasks quantum coherently. As an example, we construct a minimal feedforward quantum neural network capable of learning all 2-to-1-bit Boolean functions by optimization of network activation parameters within the supervised-learning paradigm. This model is shown to perform non-linear classification and effectively learns from multiple copies of a single training state consisting of the maximal superposition of all inputs., BUS/Quantum Delft, QCD/DiCarlo Lab, CRE Dagelijks Huurders Onderhoud, QN/Kavli Nanolab Delft, Communication QuTech, QCD/Feld Group, Design Conceptualization and Communication, Microwave Sensing, Signals & Systems, QCD/Sebastiano Lab, QN/DiCarlo Lab

Published
2023
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27. Logical-qubit operations in an error-detecting surface code

Author

Marques, J. F., Varbanov, B. M., Moreira, M. S., Ali, H., Muthusubramanian, N., Zachariadis, C., Battistel, F., Beekman, M., Haider, N., Vlothuizen, W., Bruno, A., Terhal, B. M., and DiCarlo, L.

Abstract

Future fault-tolerant quantum computers will require storing and processing quantum data in logical qubits. Here we realize a suite of logical operations on a distance-2 surface code qubit built from seven physical qubits and stabilized using repeated error-detection cycles. Logical operations include initialization into arbitrary states, measurement in the cardinal bases of the Bloch sphere and a universal set of single-qubit gates. For each type of operation, we observe higher performance for fault-tolerant variants over non-fault-tolerant variants, and quantify the difference. In particular, we demonstrate process tomography of logical gates, using the notion of a logical Pauli transfer matrix. This integration of high-fidelity logical operations with a scalable scheme for repeated stabilization is a milestone on the road to quantum error correction with higher-distance superconducting surface codes.

Published
2024
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29. The association of blood biomarkers with outcomes in older patients with solid tumors: a systematic review

Author

van Holstein, Y., primary, van den Berkmortel, P.J.E., additional, Trompet, S., additional, van Heemst, D., additional, Van den Bos, F., additional, Roemeling-van Rhijn, M., additional, De Glas, N.A., additional, Beekman, M., additional, Slagboom, P.E., additional, Portielje, J.E.A., additional, Mooijaart, S.P., additional, and Van Munster, B., additional

Published
2022
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30. Association of metabolomics mortality score with geriatric assessment and mortality in older patients with solid tumors

Author

van Holstein, Y., primary, Mooijaart, S.P., additional, Van Oevelen, M., additional, Van Deudekom, F.J., additional, Vojinovic, D., additional, Van den Bos, F., additional, Labots, G., additional, De Glas, N.A., additional, Beekman, M., additional, Van Munster, B., additional, Slagboom, P.E., additional, Portielje, J.E.A., additional, and Trompet, S., additional

Published
2022
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33. Pooled analysis of epigenome-wide association studies of food consumption in KORA, TwinsUK and LLS

Author

Hellbach, F., Sinke, L., Costeira, R., Baumeister, S.E., Beekman, M., Louca, P., Leeming, E.R., Mompeo, O., Berry, S., Wilson, R., Wawro, N., Freuer, D., Hauner, H., Peters, A., Winkelmann, J., Koenig, W., Meisinger, C., Waldenberger, M., Heijmans, B.T., Slagboom, P.E., Bell, J.T., and Linseisen, J.

Subjects
Nutrition and Dietetics, Medicine (miscellaneous), Humans, Diet, Ewas, Food Group, High-fat Foods, ddc:610, Food group, High-fat foods, EWAS
Abstract

Purpose Examining epigenetic patterns is a crucial step in identifying molecular changes of disease pathophysiology, with DNA methylation as the most accessible epigenetic measure. Diet is suggested to affect metabolism and health via epigenetic modifications. Thus, our aim was to explore the association between food consumption and DNA methylation. Methods Epigenome-wide association studies were conducted in three cohorts: KORA FF4, TwinsUK, and Leiden Longevity Study, and 37 dietary exposures were evaluated. Food group definition was harmonized across the three cohorts. DNA methylation was measured using Infinium MethylationEPIC BeadChip in KORA and Infinium HumanMethylation450 BeadChip in the Leiden study and the TwinsUK study. Overall, data from 2293 middle-aged men and women were included. A fixed-effects meta-analysis pooled study-specific estimates. The significance threshold was set at 0.05 for false-discovery rate-adjusted p values per food group. Results We identified significant associations between the methylation level of CpG sites and the consumption of onions and garlic (2), nuts and seeds (18), milk (1), cream (11), plant oils (4), butter (13), and alcoholic beverages (27). The signals targeted genes of metabolic health relevance, for example, GLI1, RPTOR, and DIO1, among others. Conclusion This EWAS is unique with its focus on food groups that are part of a Western diet. Significant findings were mostly related to food groups with a high-fat content.

Published
2022

35. Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS

Author

Hop, P.J., Zwamborn, R.A.J., Hannon, E., Shireby, G.L., Nabais, M.F., Walker, E.M., van Rheenen, W., van Vugt, J.J.F.A., Dekker, A.M., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Moisse, M., Baird, D., Al Khleifat, A., Iacoangeli, A., Ticozzi, N., Ratti, A., Cooper-Knock, J., Morrison, K.E., Shaw, P.J., Basak, A.N., Chiò, A., Calvo, A., Moglia, C., Canosa, A., Brunetti, M., Grassano, M., Gotkine, M., Lerner, Y., Zabari, M., Vourc’h, P., Corcia, P., Couratier, P., Mora Pardina, J.S., Salas, T., Dion, P., Ross, J.P., Henderson, R.D., Mathers, S., McCombe, P.A., Needham, M., Nicholson, G., Rowe, D.B., Pamphlett, R., Mather, K.A., Sachdev, P.S., Furlong, S., Garton, F.C., Henders, A.K., Lin, T., Ngo, S.T., Steyn, F.J., Wallace, L., Williams, K.L., Neto, M.M., Cauchi, R.J., Blair, I.P., Kiernan, M.C., Drory, V., Povedano, M., de Carvalho, M., Pinto, S., Weber, M., Rouleau, G.A., Silani, V., Landers, J.E., Shaw, C.E., Andersen, P.M., McRae, A.F., van Es, M.A., Pasterkamp, R.J., Wray, N.R., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Tsai, E., Runz, H., Al-Chalabi, A., van den Berg, L.H., Van Damme, P., Mill, J., Veldink, J.H., Heijmans, B.T., t Hoen, P.A.C., van Meurs, J., Jansen, R., Franke, L., Boomsma, D.I., Pool, R., van Dongen, J., Hottenga, J.J., van Greevenbroek, M.M.J., Stehouwer, C.D.A., van der Kallen, C.J.H., Schalkwijk, C.G., Wijmenga, C., Zhernakova, S., Tigchelaar, E.F., Slagboom, P.E., Beekman, M., Deelen, J., Van Heemst, D., van Duijn, C.M., Hofman, B.A., Isaacs, A., Uitterlinden, A.G., van Meurs, J.B.C., Jhamai, P.M., Verbiest, M., Suchiman, H.E.D., Verkerk, M., van der Breggen, R., van Rooij, J., Lakenberg, N., Mei, H., van Iterson, M., van Galen, M., Bot, J., Zhernakova, D.V., van ‘t Hof, P., Deelen, P., Nooren, I., Moed, M., Vermaat, M., Luijk, R., Jan Bonder, M., van Dijk, F., Arindrarto, W., Kielbasa, S.M., Swertz, M.A., van Zwet, E.W., Hoen, P.A.C., Bensimon, G., Chio, A., Smith, G.D., Hop, P.J., Zwamborn, R.A.J., Hannon, E., Shireby, G.L., Nabais, M.F., Walker, E.M., van Rheenen, W., van Vugt, J.J.F.A., Dekker, A.M., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Moisse, M., Baird, D., Al Khleifat, A., Iacoangeli, A., Ticozzi, N., Ratti, A., Cooper-Knock, J., Morrison, K.E., Shaw, P.J., Basak, A.N., Chiò, A., Calvo, A., Moglia, C., Canosa, A., Brunetti, M., Grassano, M., Gotkine, M., Lerner, Y., Zabari, M., Vourc’h, P., Corcia, P., Couratier, P., Mora Pardina, J.S., Salas, T., Dion, P., Ross, J.P., Henderson, R.D., Mathers, S., McCombe, P.A., Needham, M., Nicholson, G., Rowe, D.B., Pamphlett, R., Mather, K.A., Sachdev, P.S., Furlong, S., Garton, F.C., Henders, A.K., Lin, T., Ngo, S.T., Steyn, F.J., Wallace, L., Williams, K.L., Neto, M.M., Cauchi, R.J., Blair, I.P., Kiernan, M.C., Drory, V., Povedano, M., de Carvalho, M., Pinto, S., Weber, M., Rouleau, G.A., Silani, V., Landers, J.E., Shaw, C.E., Andersen, P.M., McRae, A.F., van Es, M.A., Pasterkamp, R.J., Wray, N.R., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Tsai, E., Runz, H., Al-Chalabi, A., van den Berg, L.H., Van Damme, P., Mill, J., Veldink, J.H., Heijmans, B.T., t Hoen, P.A.C., van Meurs, J., Jansen, R., Franke, L., Boomsma, D.I., Pool, R., van Dongen, J., Hottenga, J.J., van Greevenbroek, M.M.J., Stehouwer, C.D.A., van der Kallen, C.J.H., Schalkwijk, C.G., Wijmenga, C., Zhernakova, S., Tigchelaar, E.F., Slagboom, P.E., Beekman, M., Deelen, J., Van Heemst, D., van Duijn, C.M., Hofman, B.A., Isaacs, A., Uitterlinden, A.G., van Meurs, J.B.C., Jhamai, P.M., Verbiest, M., Suchiman, H.E.D., Verkerk, M., van der Breggen, R., van Rooij, J., Lakenberg, N., Mei, H., van Iterson, M., van Galen, M., Bot, J., Zhernakova, D.V., van ‘t Hof, P., Deelen, P., Nooren, I., Moed, M., Vermaat, M., Luijk, R., Jan Bonder, M., van Dijk, F., Arindrarto, W., Kielbasa, S.M., Swertz, M.A., van Zwet, E.W., Hoen, P.A.C., Bensimon, G., Chio, A., and Smith, G.D.

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation–based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.

Published
2022

36. 1H-NMR metabolomics-based surrogates to impute common clinical risk factors and endpoints

Author

Bizzarri, D. (author), Reinders, M.J.T. (author), Beekman, M. (author), Slagboom, P. E. (author), van den Akker, E.B. (author), Bizzarri, D. (author), Reinders, M.J.T. (author), Beekman, M. (author), Slagboom, P. E. (author), and van den Akker, E.B. (author)

Abstract

Background: Missing or incomplete phenotypic information can severely deteriorate the statistical power in epidemiological studies. High-throughput quantification of small-molecules in bio-samples, i.e. ‘metabolomics’, is steadily gaining popularity, as it is highly informative for various phenotypical characteristics. Here we aim to leverage metabolomics to impute missing data in clinical variables routinely assessed in large epidemiological and clinical studies. Methods: To this end, we have employed ∼26,000 1H-NMR metabolomics samples from 28 Dutch cohorts collected within the BBMRI-NL consortium, to create 19 metabolomics-based predictors for clinical variables, including diabetes status (AUC5-Fold CV = 0·94) and lipid medication usage (AUC5-Fold CV = 0·90). Findings: Subsequent application in independent cohorts confirmed that our metabolomics-based predictors can indeed be used to impute a wide array of missing clinical variables from a single metabolomics data resource. In addition, application highlighted the potential use of our predictors to explore the effects of totally unobserved confounders in omics association studies. Finally, we show that our predictors can be used to explore risk factor profiles contributing to mortality in older participants. Interpretation: To conclude, we provide 1H-NMR metabolomics-based models to impute clinical variables routinely assessed in epidemiological studies and illustrate their merit in scenarios when phenotypic variables are partially incomplete or totally unobserved. Funding: BBMRI-NL, X-omics, VOILA, Medical Delta and the Dutch Research Council (NWO-VENI)., Pattern Recognition and Bioinformatics

Published
2022
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37. DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases

Author

Wielscher, M. (Matthias), Mandaviya, P. R. (Pooja R.), Kuehnel, B. (Brigitte), Joehanes, R. (Roby), Mustafa, R. (Rima), Robinson, O. (Oliver), Zhang, Y. (Yan), Bodinier, B. (Barbara), Walton, E. (Esther), Mishra, P. P. (Pashupati P.), Schlosser, P. (Pascal), Wilson, R. (Rory), Tsai, P.-C. (Pei-Chien), Palaniswamy, S. (Saranya), Marioni, R. E. (Riccardo E.), Fiorito, G. (Giovanni), Cugliari, G. (Giovanni), Karhunen, V. (Ville), Ghanbari, M. (Mohsen), Psaty, B. M. (Bruce M.), Loh, M. (Marie), Bis, J. C. (Joshua C.), Lehne, B. (Benjamin), Sotoodehnia, N. (Nona), Deary, I. J. (Ian J.), Chadeau-Hyam, M. (Marc), Brody, J. A. (Jennifer A.), Cardona, A. (Alexia), Selvin, E. (Elizabeth), Smith, A. K. (Alicia K.), Miller, A. H. (Andrew H.), Torres, M. A. (Mylin A.), Marouli, E. (Eirini), Gao, X. (Xin), van Meurs, J. B. (Joyce B. J.), Graf-Schindler, J. (Johanna), Rathmann, W. (Wolfgang), Koenig, W. (Wolfgang), Peters, A. (Annette), Weninger, W. (Wolfgang), Farlik, M. (Matthias), Zhang, T. (Tao), Chen, W. (Wei), Xia, Y. (Yujing), Teumer, A. (Alexander), Nauck, M. (Matthias), Grabe, H. J. (Hans J.), Doerr, M. (Macus), Lehtimaki, T. (Terho), Guan, W. (Weihua), Milani, L. (Lili), Tanaka, T. (Toshiko), Fisher, K. (Krista), Waite, L. L. (Lindsay L.), Kasela, S. (Silva), Vineis, P. (Paolo), Verweij, N. (Niek), van der Harst, P. (Pim), Iacoviello, L. (Licia), Sacerdote, C. (Carlotta), Panico, S. (Salvatore), Krogh, V. (Vittorio), Tumino, R. (Rosario), Tzala, E. (Evangelia), Matullo, G. (Giuseppe), Hurme, M. A. (Mikko A.), Raitakari, O. T. (Olli T.), Colicino, E. (Elena), Baccarelli, A. A. (Andrea A.), Kahonen, M. (Mika), Herzig, K.-H. (Karl-Heinz), Li, S. (Shengxu), BIOS consortium, Conneely, K. N. (Karen N.), Kooner, J. S. (Jaspal S.), Kottgen, A. (Anna), Heijmans, B. T. (Bastiaan T.), Deloukas, P. (Panos), Relton, C. (Caroline), Ong, K. K. (Ken K.), Bell, J. T. (Jordana T.), Boerwinkle, E. (Eric), Elliott, P. (Paul), Brenner, H. (Hermann), Beekman, M. (Marian), Levy, D. (Daniel), Waldenberger, M. (Melanie), Chambers, J. C. (John C.), Dehghan, A. (Abbas), Järvelin, M.-R. (Marjo-Riitta), Wielscher, M. (Matthias), Mandaviya, P. R. (Pooja R.), Kuehnel, B. (Brigitte), Joehanes, R. (Roby), Mustafa, R. (Rima), Robinson, O. (Oliver), Zhang, Y. (Yan), Bodinier, B. (Barbara), Walton, E. (Esther), Mishra, P. P. (Pashupati P.), Schlosser, P. (Pascal), Wilson, R. (Rory), Tsai, P.-C. (Pei-Chien), Palaniswamy, S. (Saranya), Marioni, R. E. (Riccardo E.), Fiorito, G. (Giovanni), Cugliari, G. (Giovanni), Karhunen, V. (Ville), Ghanbari, M. (Mohsen), Psaty, B. M. (Bruce M.), Loh, M. (Marie), Bis, J. C. (Joshua C.), Lehne, B. (Benjamin), Sotoodehnia, N. (Nona), Deary, I. J. (Ian J.), Chadeau-Hyam, M. (Marc), Brody, J. A. (Jennifer A.), Cardona, A. (Alexia), Selvin, E. (Elizabeth), Smith, A. K. (Alicia K.), Miller, A. H. (Andrew H.), Torres, M. A. (Mylin A.), Marouli, E. (Eirini), Gao, X. (Xin), van Meurs, J. B. (Joyce B. J.), Graf-Schindler, J. (Johanna), Rathmann, W. (Wolfgang), Koenig, W. (Wolfgang), Peters, A. (Annette), Weninger, W. (Wolfgang), Farlik, M. (Matthias), Zhang, T. (Tao), Chen, W. (Wei), Xia, Y. (Yujing), Teumer, A. (Alexander), Nauck, M. (Matthias), Grabe, H. J. (Hans J.), Doerr, M. (Macus), Lehtimaki, T. (Terho), Guan, W. (Weihua), Milani, L. (Lili), Tanaka, T. (Toshiko), Fisher, K. (Krista), Waite, L. L. (Lindsay L.), Kasela, S. (Silva), Vineis, P. (Paolo), Verweij, N. (Niek), van der Harst, P. (Pim), Iacoviello, L. (Licia), Sacerdote, C. (Carlotta), Panico, S. (Salvatore), Krogh, V. (Vittorio), Tumino, R. (Rosario), Tzala, E. (Evangelia), Matullo, G. (Giuseppe), Hurme, M. A. (Mikko A.), Raitakari, O. T. (Olli T.), Colicino, E. (Elena), Baccarelli, A. A. (Andrea A.), Kahonen, M. (Mika), Herzig, K.-H. (Karl-Heinz), Li, S. (Shengxu), BIOS consortium, Conneely, K. N. (Karen N.), Kooner, J. S. (Jaspal S.), Kottgen, A. (Anna), Heijmans, B. T. (Bastiaan T.), Deloukas, P. (Panos), Relton, C. (Caroline), Ong, K. K. (Ken K.), Bell, J. T. (Jordana T.), Boerwinkle, E. (Eric), Elliott, P. (Paul), Brenner, H. (Hermann), Beekman, M. (Marian), Levy, D. (Daniel), Waldenberger, M. (Melanie), Chambers, J. C. (John C.), Dehghan, A. (Abbas), and Järvelin, M.-R. (Marjo-Riitta)

Abstract

We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.

Published
2022

38. MiMIR: R-shiny application to infer risk factors and endpoints from Nightingale Health's 1H-NMR metabolomics data

Author

Bizzarri, D. (author), Reinders, M.J.T. (author), Beekman, M. (author), Slagboom, P. E. (author), van den Akker, E.B. (author), Bizzarri, D. (author), Reinders, M.J.T. (author), Beekman, M. (author), Slagboom, P. E. (author), and van den Akker, E.B. (author)

Abstract

Motivation: 1H-NMR metabolomics is rapidly becoming a standard resource in large epidemiological studies to acquire metabolic profiles in large numbers of samples in a relatively low-priced and standardized manner. Concomitantly, metabolomics-based models are increasingly developed that capture disease risk or clinical risk factors. These developments raise the need for user-friendly toolbox to inspect new 1H-NMR metabolomics data and project a wide array of previously established risk models. Results: We present MiMIR (Metabolomics-based Models for Imputing Risk), a graphical user interface that provides an intuitive framework for ad hoc statistical analysis of Nightingale Health's 1H-NMR metabolomics data and allows for the projection and calibration of 24 pre-trained metabolomics-based models, without any pre-required programming knowledge., Pattern Recognition and Bioinformatics

Published
2022
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39. A recurrent neural network architecture to model physical activity energy expenditure in older people

Author

Paraschiakos, S., Sá, C.R. de, Okai, J., Slagboom, P.E., Beekman, M., and Knobbe, A.J.

Subjects
Accelerometer, Recurrent neural networks, Monitoring older adults, Computer Networks and Communications, Wearables, Physical activity energy expenditure, Indirect calorimetry, Computer Science Applications, Information Systems
Abstract

Through the quantification of physical activity energy expenditure (PAEE), health care monitoring has the potential to stimulate vital and healthy ageing, inducing behavioural changes in older people and linking these to personal health gains. To be able to measure PAEE in a health care perspective, methods from wearable accelerometers have been developed, however, mainly targeted towards younger people. Since elderly subjects differ in energy requirements and range of physical activities, the current models may not be suitable for estimating PAEE among the elderly. Furthermore, currently available methods seem to be either simple but non-generalizable or require elaborate (manual) feature construction steps. Because past activities influence present PAEE, we propose a modeling approach known for its ability to model sequential data, the recurrent neural network (RNN). To train the RNN for an elderly population, we used the growing old together validation (GOTOV) dataset with 34 healthy participants of 60 years and older (mean 65 years old), performing 16 different activities. We used accelerometers placed on wrist and ankle, and measurements of energy counts by means of indirect calorimetry. After optimization, we propose an architecture consisting of an RNN with 3 GRU layers and a feedforward network combining both accelerometer and participant-level data. Our efforts included switching mean to standard deviation for down-sampling the input data and combining temporal and static data (person-specific details such as age, weight, BMI). The resulting architecture produces accurate PAEE estimations while decreasing training input and time by a factor of 10. Subsequently, compared to the state-of-the-art, it is capable to integrate longer activity data which lead to more accurate estimations of low intensity activities EE. It can thus be employed to investigate associations of PAEE with vitality parameters of older people related to metabolic and cognitive health and mental well-being.

Published
2022

40. 1H-NMR metabolomics-based surrogates to impute common clinical risk factors and endpoints

Author

Bizzarri, D., Reinders, M.J.T., Beekman, M., Slagboom, P.E., BBMRI-NL, and Akker, E.B. van den

Subjects
Medicine (General), metabolic surrogates, posterior probability obtained applying the models, Magnetic Resonance Spectroscopy, Epidemiology, Proton Magnetic Resonance Spectroscopy, chol, cholesterol, General Biochemistry, Genetics and Molecular Biology, Article, R5-920, H-1-NMR metabolomics, Risk Factors, Humans, Metabolomics, wbc, white blood cells, Missing values, hsCRP, high-sensitivity C-Reactive Protein, MetaboWAS, metabolome-wide association studies, med, medication (e.g. lipid or blood pressure lowering medication, Association studies, Aged, eGFR, estimated Glomerular Filtration Rate, hgb, haemoglobin, General Medicine, 1H-NMR metabolomics, Regression models, H-NMR metabolomics, Surrogate clinical variables, Medicine, T2D, Type 2 Diabetes status, BMI, Body Mass Index
Abstract

Background: Missing or incomplete phenotypic information can severely deteriorate the statistical power in epidemiological studies. High-throughput quantification of small-molecules in bio-samples, i.e. ‘metabolomics’, is steadily gaining popularity, as it is highly informative for various phenotypical characteristics. Here we aim to leverage metabolomics to impute missing data in clinical variables routinely assessed in large epidemiological and clinical studies. Methods: To this end, we have employed ∼26,000 1H-NMR metabolomics samples from 28 Dutch cohorts collected within the BBMRI-NL consortium, to create 19 metabolomics-based predictors for clinical variables, including diabetes status (AUC5-Fold CV = 0·94) and lipid medication usage (AUC5-Fold CV = 0·90). Findings: Subsequent application in independent cohorts confirmed that our metabolomics-based predictors can indeed be used to impute a wide array of missing clinical variables from a single metabolomics data resource. In addition, application highlighted the potential use of our predictors to explore the effects of totally unobserved confounders in omics association studies. Finally, we show that our predictors can be used to explore risk factor profiles contributing to mortality in older participants. Interpretation: To conclude, we provide 1H-NMR metabolomics-based models to impute clinical variables routinely assessed in epidemiological studies and illustrate their merit in scenarios when phenotypic variables are partially incomplete or totally unobserved. Funding: BBMRI-NL, X-omics, VOILA, Medical Delta and the Dutch Research Council (NWO-VENI).

Published
2021

41. Logical-qubit operations in an error-detecting surface code

Author

Marques, J. F., primary, Varbanov, B. M., additional, Moreira, M. S., additional, Ali, H., additional, Muthusubramanian, N., additional, Zachariadis, C., additional, Battistel, F., additional, Beekman, M., additional, Haider, N., additional, Vlothuizen, W., additional, Bruno, A., additional, Terhal, B. M., additional, and DiCarlo, L., additional

Published
2021
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46. 62 (PB-062) Poster - Survival after risk-reducing salpingo-oophorectomy for BRCA1/2 germline pathogenic variant carriers with a history of breast cancer: introducing an alternative approach for confounding adjustment in observational studies.

Author

Heemskerk-Gerritsen, A., Terra, L., Beekman, M., Maas, A., van Leeuwen, F., and Hooning, M.

Subjects
*SURVIVAL, *SALPINGO-oophorectomy, *BRCA genes, *BREAST tumors, *SCIENTIFIC observation, *CONFERENCES & conventions, *GENETIC mutation, *PATHOGENESIS
Published
2024
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47. The association of overweight, obesity, and long-term obesity with SARS-CoV-2 infection: a meta-analysis of 9 population-based cohorts from the Netherlands Cohorts Consortium.

Author

Loef B, Boer JMA, Beekman M, Campman SL, Hoogendijk EO, Huider F, Pagen DME, Splinter MJ, van der Velde JHPM, Boomsma DI, Dagnelie PC, van Dongen J, de Geus EJC, Huisman M, Ikram MA, Koster A, Licher S, Mierau JO, de Mutsert R, Picavet HSJ, Rosendaal FR, Schram MT, Slagboom PE, van der Spoel E, Stronks K, Verschuren WMM, and van den Berg SW

Abstract

Background: Obesity may affect an individual's immune response and subsequent risk of infection, such as a SARS-CoV-2 infection. It is less clear whether overweight and long-term obesity also constitute risk factors. We investigated the association between the degree and duration of overweight and obesity and SARS-CoV-2 infection., Methods: We analyzed data from nine prospective population-based cohorts of the Netherlands Cohorts Consortium, with a total of 99,570 participants, following a standardized procedure. Body mass index (BMI) and waist circumference (WC) were assessed two times before the pandemic, with approximately 5 years between measurements. SARS-CoV-2 infection was defined by self-report as a positive PCR or rapid-antigen test or as COVID-19 ascertained by a physician between March 2020 and January 2023. For three cohorts, information on SARS-CoV-2 infection by serology was available. Results were pooled using random-effects meta-analyses and adjusted for age, sex, educational level, and number of SARS-CoV-2 infection measurements., Results: Individuals with overweight (25 ≤ BMI < 30 kg/m 2 ) (odds ratio (OR) = 1.08, 95%-confidence interval (CI) 1.04-1.13) or obesity (BMI ≥ 30 kg/m 2 ) (OR = 1.43, 95%-CI 1.18-1.75) were more likely to report SARS-CoV-2 infection than individuals with a healthy body weight. We observed comparable ORs for abdominal overweight (men: 94 cm≤WC < 102 cm, women: 80 cm≤WC < 88 cm) (OR = 1.09, 95%-CI 1.04-1.14, I 2  = 0%) and abdominal obesity (men: WC ≥ 102 cm, women: WC ≥ 88 cm) (OR = 1.24, 95%-CI 0.999-1.55, I 2  = 57%). Individuals with obesity long before the pandemic, but with a healthy body weight or overweight just before the pandemic, were not at increased risk., Conclusion: Overweight and obesity were associated with increased risk of SARS-CoV-2 infection with stronger associations for obesity. Individuals with a healthier weight prior to the pandemic but previous obesity did not have an increased risk of SARS-CoV-2, suggesting that weight loss in those with obesity reduces infection risk. These results underline the importance of obesity prevention and weight management for public health., (© 2024. The Author(s).)

Published
2024
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48. Design of the VOILA-intervention study: A 12-week nutrition and resistance exercise intervention in metabolic or mobility compromised Dutch older adults and the response on immune-metabolic, gut and muscle health parameters.

Author

Kramer CS, Monsegue A, Morwani-Mangnani J, Grootswagers P, Beekman M, Slagboom PE, Verdijk LB, and de Groot LC

Abstract

Background: Exercise and nutrition interventions can slow ageing-induced decline in physiology. However, effects are heterogeneous and usually studied separately per outcome domain. In the VOILA study, we simultaneously study various health outcomes relevant for older adults and the inter-individual heterogeneity in response to a lifestyle intervention., Methods: VOILA is a 12-week lifestyle intervention in 3 groups of older adults (≥60 years), with compromised mobility (n=50), compromised metabolic health (n=50), or recovering from total knee replacement (TKR, n=70, of which 20 randomized to standard care only). The intervention includes high-intensity resistance exercise training thrice weekly, nutritional counselling, and nutritional supplements every morning and evening (including 20-25g whey protein and (evening only) 5.5g Biotis™ GOS). We measure immune-metabolic, gut health, muscle mass and physical functioning at baseline and after completion of the intervention/standard care. An additional reference group of healthy older adults (n=50) will undergo baseline measurements only., Discussion: Improvements in various physiological systems are expected, but with differences between groups/individuals. This study will provide insights into how the physiological state of older adults influences the extent of lifestyle-induced health improvements to create better tailored interventions to attenuate biological ageing and improve the health span of subgroups and individuals., (Copyright © 2024. Published by Elsevier B.V.)

Published
2024
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49. Biomarkers of endothelial dysfunction and cognition: A two-step IPD meta-analysis.

Author

Beran M, Jansen WJ, Oomens JE, Moonen JEF, Slagboom PE, Huisman M, Kok AAL, Nooyens ACJ, Verschuren WMM, Stehouwer CDA, Schalkwijk C, Köhler S, Beekman M, Slagboom PE, Wolters FJ, Ikram MA, Vallerga CL, van Meurs JBJ, Ghanbari M, Vonk JMJ, Geerlings MI, van Sloten TT, and Schram MT

Abstract

Introduction: This study assessed the association of plasma biomarkers of endothelial dysfunction with cognitive performance and decline., Methods: Data from 9414 individuals from eight Dutch cohorts were included (Ø  age-range: 57-93 years). Plasma biomarkers of endothelial dysfunction (soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin) were combined into a standardized composite score. Cognitive outcomes included executive function, processing speed, immediate and delayed memory, attention, and language. Linear regressions and linear mixed models were run in the individual cohorts and standardized coefficients were subsequently pooled using random-effects meta-analyses., Results: A higher endothelial dysfunction composite score was cross-sectionally associated with worse performance on executive function, processing speed, delayed memory, and attention, but not immediate memory or language (pooled β-range: -0.04, -0.02). We found no association with change in cognition over time., Discussion: This comprehensive two-step, individual participant data (IPD) meta-analysis showed a small, consistent cross-sectional association between endothelial dysfunction and worse cognitive performance across multiple domains but no support for a longitudinal association., Highlights: Prior evidence on endothelial dysfunction (ED) biomarkers and cognition is conflicting. This two-step, individual participant data (IPD) meta-analysis used data from eight Dutch cohorts. ED was consistently associated with concurrent cognition. ED was not associated with a change in cognition over time. The association of ED with current cognition may be generic., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Published
2024
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50. NMR metabolomics-guided DNA methylation mortality predictors.

Author

Bizzarri D, Reinders MJT, Kuiper L, Beekman M, Deelen J, van Meurs JBJ, van Dongen J, Pool R, Boomsma DI, Ghanbari M, Franke L, Slagboom PE, and van den Akker EB

Subjects
Humans, Male, Female, Aged, Mortality, Metabolome, Middle Aged, Magnetic Resonance Spectroscopy methods, Aged, 80 and over, DNA Methylation, Metabolomics methods, Biomarkers
Abstract

Background: 1 H-NMR metabolomics and DNA methylation in blood are widely known biomarkers predicting age-related physiological decline and mortality yet exert mutually independent mortality and frailty signals., Methods: Leveraging multi-omics data in four Dutch population studies (N = 5238, ∼40% of which male) we investigated whether the mortality signal captured by 1 H-NMR metabolomics could guide the construction of DNA methylation-based mortality predictors., Findings: We trained DNA methylation-based surrogates for 64 metabolomic analytes and found that analytes marking inflammation, fluid balance, or HDL/VLDL metabolism could be accurately reconstructed using DNA-methylation assays. Interestingly, a previously reported multi-analyte score indicating mortality risk (MetaboHealth) could also be accurately reconstructed. Sixteen of our derived surrogates, including the MetaboHealth surrogate, showed significant associations with mortality, independent of relevant covariates., Interpretation: The addition of our metabolic analyte-derived surrogates to the well-established epigenetic clock GrimAge demonstrates that our surrogates potentially represent valuable mortality signal., Funding: BBMRI-NL, X-omics, VOILA, Medical Delta, NWO, ERC., Competing Interests: Declaration of interests Authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2024
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