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1. Computing resonant modes of accelerator cavities by solving nonlinear eigenvalue problems via rational approximation

Author

Van Beeumen, R, Marques, O, Ng, EG, Yang, C, Bai, Z, Ge, L, Kononenko, O, Li, Z, Ng, CK, and Xiao, L

Subjects
Accelerator modeling, Nonlinear eigenvalue problem, CORK method, Applied Mathematics, Mathematical Sciences, Physical Sciences, Engineering
Abstract

We present an efficient and reliable algorithm for solving a class of nonlinear eigenvalue problems arising from the modeling of particle accelerator cavities. The eigenvalue nonlinearity in these problems results from the use of waveguides to couple external power sources or to allow certain excited electromagnetic modes to exit the cavity. We use a rational approximation to reduce the nonlinear eigenvalue problem first to a rational eigenvalue problem. We then apply a special linearization procedure to turn the rational eigenvalue problem into a larger linear eigenvalue problem with the same eigenvalues, which can be solved by existing iterative methods. By using a compact scheme to represent both the linearized operator and the eigenvectors to be computed, we obtain a numerical method that only involves solving linear systems of equations of the same dimension as the original nonlinear eigenvalue problem. We refer to this method as a compact rational Krylov (CORK) method. We implemented the CORK method in the Omega3P module of the Advanced Computational Electromagnetic 3D Parallel (ACE3P) simulation suite and validated it by comparing the computed cavity resonant frequencies and damping Q factors of a small model problem to those obtained from a fitting procedure that uses frequency responses computed by another ACE3P module called S3P. We also used the CORK method to compute trapped modes damped in an ideal eight 9-cell SRF cavity cryomodule. This was the first time it was possible to compute these modes directly. The damping Q factors of the computed modes match well with those measured in experiments and the difference in resonant frequencies is within the range introduced by cavity imperfection. Therefore, the CORK method is an extremely valuable tool for computational cavity design.

Published
2018

2. Design concepts for a next generation light source at LBNL

Author

Corlett, JN, Allezy, A, Arbelaez, D, Baptiste, K, Byrd, J, Daniels, C, De Santis, S, Delp, W, Denes, P, Donahue, R, Doolittle, L, Emma, PJ, Filippetto, D, Floyd, J, Harkins, J, Huang, G, Jung, JY, Li, D, Pui Lou, T, Luo, T, Marcus, G, Monroy, MT, Nishimura, H, Padmore, HA, Papadopoulos, C, Pappas, C, Paret, S, Penn, G, Placidi, M, Prestemon, S, Prosnitz, D, Qian, H, Qiang, J, Ratti, A, Reinsch, M, Robin, D, Sannibale, F, Schoenlein, RW, Serrano, C, Staples, J, Steier, C, Sun, C, Venturini, M, Waldron, WL, Wan, W, Warwick, T, Wells, R, Wilcox, R, Zimmermann, S, Zolotorev, M, Ginsburg, C, Kephart, R, Klebaner, AL, Peterson, T, Sukhanov, A, Arenius, D, Neil, GR, Powers, T, Preble, JP, Adolphsen, C, Bane, K, Ding, Y, Huang, Z, Nantista, C, Ng, CK, Nuhn, HD, Rivetta, C, and Stupakov, G

Abstract

The NGLS collaboration is developing design concepts for a multi-beamline soft x-ray FEL array powered by a superconducting linear accelerator, operating with a high bunch repetition rate of approximately 1 MHz. The CW superconducting linear accelerator design is based on developments of TESLA and ILC technology, and is supplied by an injector based on a high-brightness, highrepetition- rate photocathode electron gun. Electron bunches from the linac are distributed by RF deflecting cavities to the array of independently configurable FEL beamlines with nominal bunch rates of ∼100 kHz in each FEL, with uniform pulse spacing, and some FELs capable of operating at the full linac bunch rate. Individual FELs may be configured for different modes of operation, including self-seeded and external-laser-seeded, and each may produce high peak and average brightness x-rays with a flexible pulse format, and with pulse durations ranging from femtoseconds and shorter, to hundreds of femtoseconds. In this paper we describe current design concepts, and progress in RandD activities. Copyright © 2013 CC-BY-3.0 and by the respective authors.

Published
2013

4. Mild cognitive impairment and its management in older people

Author

Eshkoor SA, Hamid TA, Mun CY, and Ng CK

Subjects
Alzheimer Disease (AD), Asia Pacific, Cognition, Dementia, Mild Cognitive Impairment (MCI), Geriatrics, RC952-954.6
Abstract

Sima Ataollahi Eshkoor, Tengku Aizan Hamid, Chan Yoke Mun, Chee Kyun Ng Institute of Gerontology, Universiti Putra Malaysia, Selangor, Malaysia Abstract: Mild cognitive impairment (MCI) is a common condition in the elderly. It is characterized by deterioration of memory, attention, and cognitive function that is beyond what is expected based on age and educational level. MCI does not interfere significantly with individuals’ daily activities. It can act as a transitional level of evolving dementia with a range of conversion of 10%–15% per year. Thus, it is crucial to protect older people against MCI and developing dementia. The preventive interventions and appropriate treatments should improve cognitive performance, and retard or prevent progressive deficits. The avoidance of toxins, reduction of stress, prevention of somatic diseases, implementation of mental and physical exercises, as well as the use of dietary compounds like antioxidants and supplements can be protective against MCI. The modification of risk factors such as stopping smoking, as well as the treatment of deficiency in vitamins and hormones by correcting behaviors and lifestyle, can prevent cognitive decline in the elderly. The progressive increase in the growth rate of the elderly population can enhance the rate of MCI all over the world. There is no exact cure for MCI and dementia; therefore, further studies are needed in the future to determine causes of MCI and risk factors of progression from MCI to dementia. This will help to find better ways for prevention and treatment of cognitive impairment worldwide. Keywords: AD, Alzheimer’s disease, cognition, dementia, MCI

Published
2015

5. Giant Chondrosarcoma of Proximal Humerus in an Adult Female Patient: A Case Report

Author

Ng CK, Azuhairy A, Tan LH, and Nordin A

Subjects
Giant chondrosarcoma, proximal humerus, young female, forequarter amputation, Orthopedic surgery, RD701-811
Abstract

Chondrosarcoma is the third most common primary tumour of the bone, after myeloma and osteosarcoma. Most of the chondrosarcoma grow slowly and rarely metastasize, and they have an excellent prognosis after adequate surgery. However most of them are chemo or radio-resistant. We report a case of primary chondrosarcoma of proximal humerus in a 36-year-old female who presented with a six years history of left shoulder swelling and restricted range of motion. Trucut biopsy showed a well-differentiated chondrosarcoma. The patient underwent forequarter amputation of left upper limb and was started on chemotherapy following operation.

Published
2015
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6. Simulations of future particle accelerators: Issues and mitigations

Author

Sagan, D, Sagan, D, Berz, M, Cook, NM, Hao, Y, Hoffstaetter, G, Huebl, A, Huang, CK, Langston, MH, Mayes, CE, Mitchell, CE, Ng, CK, Qiang, J, Ryne, RD, Scheinker, A, Stern, E, Vay, JL, Winklehner, D, Zhang, H, Sagan, D, Sagan, D, Berz, M, Cook, NM, Hao, Y, Hoffstaetter, G, Huebl, A, Huang, CK, Langston, MH, Mayes, CE, Mitchell, CE, Ng, CK, Qiang, J, Ryne, RD, Scheinker, A, Stern, E, Vay, JL, Winklehner, D, and Zhang, H

Abstract

The ever increasing demands placed upon machine performance have resulted in the need for more comprehensive particle accelerator modeling. Computer simulations are key to the success of particle accelerators. Many aspects of particle accelerators rely on computer modeling at some point, sometimes requiring complex simulation tools and massively parallel supercomputing. Examples include the modeling of beams at extreme intensities and densities (toward the quantum degeneracy limit), and with ultra-fine control (down to the level of individual particles). In the future, adaptively tuned models might also be relied upon to provide beam measurements beyond the resolution of existing diagnostics. Much time and effort has been put into creating accelerator software tools, some of which are highly successful. However, there are also shortcomings such as the general inability of existing software to be easily modified to meet changing simulation needs. In this paper possible mitigating strategies are discussed for issues faced by the accelerator community as it endeavors to produce better and more comprehensive modeling tools. This includes lack of coordination between code developers, lack of standards to make codes portable and/or reusable, lack of documentation, among others.

Published
2021

7. Multi-objective optimization with an integrated electromagnetics and beam dynamics workflow

Author

Bizzozero, DA, Bizzozero, DA, Qiang, J, Ge, L, Li, Z, Ng, CK, Xiao, L, Bizzozero, DA, Bizzozero, DA, Qiang, J, Ge, L, Li, Z, Ng, CK, and Xiao, L

Abstract

In particle accelerators, RF cavities are used to accelerate charged particle beams to designed high energy for physical applications. In a typical accelerator design, the optimization of RF cavities and the optimization of beam dynamics are carried out in separate studies. For a more general and unrestricted accelerator design, a coupled optimization of the RF cavities and the beam parameters is required. For this coupled optimization problem, we have developed an integrated electromagnetics and beam dynamics workflow management system. Within this system, the geometries for a set of cavity components are first adjusted; the field modes are then computed with an electromagnetics program, and imported into a beam dynamics program for beam dynamics simulation. This workflow is encapsulated into a parallel multi-objective optimizer to achieve the integrated accelerator design optimization. A multi fidelity strategy is developed to improve the speed of the optimizer. This integrated global optimization capability is illustrated using a photoinjector design example and yields an improved design.

Published
2021

8. Cell-Extrinsic Differentiation Block Mediated by EphA3 in Pre-Leukaemic Thymus Contributes to Disease Progression

Author

Zamora, ACP, Ranasinghe, H, Lisle, JE, Ng, CK, Huang, S, Wadlow, R, Scott, AM, Boyd, AW, Slape, C, Zamora, ACP, Ranasinghe, H, Lisle, JE, Ng, CK, Huang, S, Wadlow, R, Scott, AM, Boyd, AW, and Slape, C

Abstract

We recently characterised the NUP98-HOXD13 (NHD13) mouse as a model of T-cell pre-leukaemia, featuring thymocytes that can engraft in recipient animals and progress to T-cell acute lymphoblastic leukaemia (T-ALL). However, loss of this engraftment ability by deletion of Lyl1 did not result in any loss of leukemogenesis activity. In the present study, we observe that NHD13 thymocytes overexpress EPHA3, and we characterise thymocyte behaviour in NHD13 mice with deletion of EphA3, which show a markedly reduced incidence of T-ALL. Deletion of EphA3 from the NHD13 mice does not prevent the abnormal accumulation or transplantation ability of these thymocytes. However, upon transplantation, these cells are unable to block the normal progression of recipient wild type (WT) progenitor cells through the normal developmental pathway. This is in contrast to the EphA3+/+ NHD13 thymocytes, which block the progression of incoming WT progenitors past the DN1 stage. Therefore, EphA3 is not critical for classical self-renewal, but is essential for mediating an interaction between the abnormally self-renewing cells and healthy progenitors-an interaction that results in a failure of the healthy cells to differentiate normally. We speculate that this may orchestrate a loss of healthy cell competition, which in itself has been demonstrated to be oncogenic, and that this may explain the decrease in T-ALL incidence in the absence of EphA3. We suggest that pre-leukaemic self-renewal in this model is a complex interplay of cell-intrinsic and -extrinsic factors, and that multiple redundant pathways to leukaemogenesis are active.

Published
2021

9. Water-Borne Nanocoating for Rapid Inactivation of SARS-CoV-2 and Other Viruses

Author

Bobrin, VA, Chen, S-P, Reyes, CFG, Sun, B, Ng, CK, Kim, Y, Purcell, D, Jia, Z, Gu, W, Armstrong, JW, McAuley, J, Monteiro, MJ, Bobrin, VA, Chen, S-P, Reyes, CFG, Sun, B, Ng, CK, Kim, Y, Purcell, D, Jia, Z, Gu, W, Armstrong, JW, McAuley, J, and Monteiro, MJ

Abstract

The rise in coronavirus variants has resulted in surges of the disease across the globe. The mutations in the spike protein on the surface of the virion membrane not only allow for greater transmission but also raise concerns about vaccine effectiveness. Preventing the spread of SARS-CoV-2, its variants, and other viruses from person to person via airborne or surface transmission requires effective inactivation of the virus. Here, we report a water-borne spray-on coating for the complete inactivation of viral particles and degradation of their RNA. Our nanoworms efficiently bind and, through subsequent large nanoscale conformational changes, rupture the viral membrane and subsequently bind and degrade its RNA. Our coating completely inactivated SARS-CoV-2 (VIC01) and an evolved SARS-CoV-2 variant of concern (B.1.1.7 (alpha)), influenza A, and a surrogate capsid pseudovirus expressing the influenza A virus attachment glycoprotein, hemagglutinin. The polygalactose functionality on the nanoworms targets the conserved S2 subunit on the SARS-CoV-2 virion surface spike glycoprotein for stronger binding, and the additional attachment of guanidine groups catalyze the degradation of its RNA genome. Coating surgical masks with our nanoworms resulted in complete inactivation of VIC01 and B.1.1.7, providing a powerful control measure for SARS-CoV-2 and its variants. Inactivation was further observed for the influenza A and an AAV-HA capsid pseudovirus, providing broad viral inactivation when using the nanoworm system. The technology described here represents an environmentally friendly coating with a proposed nanomechanical mechanism for inactivation of both enveloped and capsid viruses. The functional nanoworms can be easily modified to target viruses in future pandemics, and is compatible with large scale manufacturing processes.

Published
2021

11. Static malware clustering using enhanced deep embedding method

Author

Ng, CK, Jiang, F, Zhang, LY, and Zhou, W

Subjects
Distributed Computing
Abstract

© 2019 John Wiley & Sons, Ltd. Malware refers to any software, programs, or files that are intentionally utilised to compromise the system and cause unexpected losses to end-users such as economical losses or privacy breaches. The rapid growth of malware makes it impossible to keep up with its progress merely via human interventions or manual analysis. One of the challenges for the human-oriented approaches is they will cause backlog and inability to keep up with the development traces of the malware. Hence, an efficient method is needed urgently to analyse effectively and identify accurately the malware in their domain. Malware clustering has been extensively studied in the machine learning area with regards to distance functions, grouping algorithm and cluster validation. A large number of research studies have been done via behavioral analysis for clustering to achieve high performance of malware detections. However, there is a trade-off for better detection performance between behaviorial approaches and high computational forces. Up to date, little work focuses on the deep learning representations for malware clustering. Therefore, in this paper, we propose an enhanced deep embedded clustering method to facilitate an effective and efficient malware clustering process. The new method takes advantage of linear dimensionality reduction and a customised deep neural network to learn malware representations in an orthogonal space and performs cluster assignments. Our experimental results demonstrate that the proposed clustering model outperforms the traditional K-means method with regards to the enhanced features using various auto-encoder, pre-trained weight and principle component analysis (PCA).

Published
2019

13. Short term outcome and risk factors for adverse clinical outcomes in adults with severe acute respiratory syndrome (SARS)

Author

Chan, JWM, Ng, CK, Mok, TYW, Lee, S, Chu, SYY, Law, WL, Lee, MP, and Li, PCK

Subjects
Outcome and process assessment (Health Care) -- Analysis, Statistics -- Analysis, Severe acute respiratory syndrome -- Diagnosis -- Risk factors, Health, Diagnosis, Analysis, Risk factors
Abstract

Background: Severe acute respiratory syndrome (SARS) was diagnosed in Hong Kong in over 1700 patients between March and early June 2003. Methods: 115 patients diagnosed with SARS were admitted to [...]

Published
2003

15. Effective Assessment of Power Standing Device to Adults with Permanent Lower Limb Paralysis

Author

Yu Kp Jason, Ng Sw Serena, Chan Kk Simon, Ng Ck Richy, and Au Kp Jocelyn

Subjects
Evidence-based practice, business.industry, Social cost, media_common.quotation_subject, Health technology, medicine.disease, Atomic and Molecular Physics, and Optics, Promotion (rank), Scale (social sciences), Health care, medicine, Medical emergency, Electrical and Electronic Engineering, business, Psychology, Mobile device, Independent living, media_common
Abstract

Introduction: Standing routine is a known beneficial daily activity for both healthy and disabled persons, especially those with permanent lower limb paralysis. However, the p rescri p tion of standing device for adults with permanent paralysis was inadequate and non-standard in existing local practice because of lack of good design and evidence based funding support. Objective: I n view of the availability of new advances in power standing device , w e aim to perform an effective health technology assessment (HTA) from professional and users perspectives to develop the decision pathway in prescription for long term home use . Methodology: A functional test and social cost analysis was performed on one high cost new standing mobile devices in recent market . A practical workshop and surveys were performed to collect feedback from 24 healthcare professionals and 8 expert users on a spectrum of new standing mobile device . Results: From the survey results, there was consensus among all participants that ‘Standing’ as daily routine at home is essential and beneficial. 62.5% of healthcare professionals would provide training to users and their cares to facilitate users to perform standing at home . Eight factors were identified from factor analysis in affecting the choice of standing devices for home use by healthcare professionals and users. Users scored high (mean=9.25/10) in “compliance with the new power standing mobile device”. The cost analysis showed considerable savings in social costs in using even the high-cost power standing mobile device. Discussion: The group welcomed power standing device with or without mobile function to support their standing activity at home . A possible clinical decision for prescribing different standing devices with identified factors was summarized. Conclusion: M ore recent researches have reported the negative health issues associated with prolonged sitting . With more innovative product designs , the power standing device s with or without mobile function is a new concept welcomed by both healthcare professionals and user s in promotion of their health, preventing complications as well as independent living in home environment. A larger scale of HTA with structured cost-effectiveness analysis is essential to inform the healthcare resources planners.

Published
2019
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16. Countdown to 2015 country case studies: What have we learned about processes and progress towards MDGs 4 and 5?

Author

Moucheraud, C, Owen, H, Singh, NS, Ng, CK, Requejo, J, Lawn, JE, Berman, P, Salehi, A, Hong, Z, Ronsmans, C, Yanqiu, G, Kebede, H, Mann, C, Ruducha, J, Tadesse, M, Ngugi, A, Keats, E, Macharia, W, Ravishankar, N, Tole, J, Bryce, J, Colbourn, T, Daelmans, B, Kanyuka, M, Nsona, H, Askeer, N, Bhutta, Z, Bhatti, Z, Rizvi, A, De Guzman, JN, Huicho, L, Victora, C, Afnan-Holmes, H, John, T, Magoma, M, and Msemo, G

Subjects
Child health, Coverage, Health systems, Health finance, parasitic diseases, Neonatal health, Reproductive health, Maternal health, Equity, Accountability, Millennium Development Goals
Abstract

© 2016 The Author(s). Background: Countdown to 2015 was a multi-institution consortium tracking progress towards Millennium Development Goals (MDGs) 4 and 5. Case studies to explore factors contributing to progress (or lack of progress) in reproductive, maternal, newborn and child health (RMNCH) were undertaken in: Afghanistan, Bangladesh, China, Ethiopia, Kenya, Malawi, Niger, Pakistan, Peru, and Tanzania. This paper aims to identify cross-cutting themes on how and why these countries achieved or did not achieve MDG progress. Methods: Applying a standard evaluation framework, analyses of impact, coverage and equity were undertaken, including a mixed methods analysis of how these were influenced by national context and coverage determinants (including health systems, policies and financing). Results: The majority (7/10) of case study countries met MDG-4 with over two-thirds reduction in child mortality, but none met MDG-5a for 75 % reduction in maternal mortality, although six countries achieved >75 % of this target. None achieved MDG-5b regarding reproductive health. Rates of reduction in neonatal mortality were half or less that for post-neonatal child mortality. Coverage increased most for interventions administered at lower levels of the health system (e.g., immunisation, insecticide treated nets), and these experienced substantial political and financial support. These interventions were associated with ~30-40 % of child lives saved in 2012 compared to 2000, in Ethiopia, Malawi, Peru and Tanzania. Intrapartum care for mothers and newborns - which require higher-level health workers, more infrastructure, and increased community engagement - showed variable increases in coverage, and persistent equity gaps. Countries have explored different approaches to address these problems, including shifting interventions to the community setting and tasks to lower-level health workers. Conclusions: These Countdown case studies underline the importance of consistent national investment and global attention for achieving improvements in RMNCH. Interventions with major global investments achieved higher levels of coverage, reduced equity gaps and improvements in associated health outcomes. Given many competing priorities for the Sustainable Development Goals era, it is essential to maintain attention to the unfinished RMNCH agenda, particularly health systems improvements for maternal and neonatal outcomes where progress has been slower, and to invest in data collection for monitoring progress and for rigorous analyses of how progress is achieved in different contexts.

Published
2016
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17. Abstract P1-05-03: The genomic landscape of breast metaplastic carcinoma

Author

Geyer, FC, primary, Ng, CK, additional, Piscuoglio, S, additional, Wen, YH, additional, Wen, H-C, additional, Pareja, F, additional, Eberle, CA, additional, Burke, KA, additional, Lim, RS, additional, Natrajan, R, additional, Mariani, O, additional, Brogi, E, additional, Norton, L, additional, Vincent-Salomon, A, additional, Weigelt, B, additional, and Reis-Filho, JS, additional

Published
2017
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18. Abstract S2-02: The landscape of somatic genetic alterations in BRCA1 and BRCA2 breast cancers

Author

Geyer, FC, primary, Burke, KA, additional, Macedo, GS, additional, Piscuoglio, S, additional, Ng, CK, additional, Martelotto, LG, additional, Papanastatiou, AD, additional, De Filippo, MR, additional, Schultheis, AM, additional, Brogi, E, additional, Robson, M, additional, Wen, YH, additional, Weigelt, B, additional, Schnitt, SJ, additional, Tung, N, additional, and Reis-Filho, JS, additional

Published
2017
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19. Ezetimibe added to statin therapy after acute coronary syndromes

Author

Cannon, Christopher P., Blazing, Michael A., Giugliano, Robert P., Mccagg, Amy, White, Jennifer A., Theroux, Pierre, Darius, Harald, Lewis, Basil S., Ophuis, Ton Oude, Jukema, J. Wouter, De Ferrari, Gaetano M., Ruzyllo, Witold, De Lucca, Paul, Kyungah, Im, Bohula, Erin A., Reist, Craig, Wiviott, Stephen D., Tershakovec, Andrew M., Musliner, Thomas A., Braunwald, Eugene, Califf, Musliner T, Robert M., Tershakovec, A, Gurfinkel, E, Aylward, P, Tonkin, A, Maurer, G, Van de Werf, F, Nicolau, Jc, Theroux, P, Genest, J, Armstrong, P, Corbalan, R, Isaza, D, Spinar, J, Grande, P, Voitk, J, Kesaniemi, A, Bassand, Jp, Farnier, M, Darius, H, Keltai, M, Mathur, A, Mittal, S, Reddy, K, Lewis, B, De Ferrari GM, Ophuis, To, Jukema, J, White, H, Pedersen, T, Britto, F, Ruzyllo, W, Carrageta, M, Duris, T, Dalby, A, Seung, Kb, Lopez-Sendon, J, Dellborg, M, Mach, F, Guneri, S, Parkhomenko, A, Brady, A, Cannon, C, Blazing, M, Ballantyne, C, de Lemos, J, Kleiman, N, Mcguire, Dk, Centeno, E, Casalins, M, Cartasegna, L, Beltrano, Mc, Guerrero, R, Fanuele, M, Berra, F, Egido, J, Colombo, H, Dellatorre, M, Terns, P, Blumberg, E, Reges, P, Azize, G, Ramos, H, Fernandez, R, Carlessi, C, Milesi, R, Schmuck, R, Duronto, E, Procopio, G, Carlevaro, O, Maffeo, H, Beloscar, J, Viso, M, Hominal, M, Castoldi, M, Bluguermann, J, Mauro, D, Macin, S, Cocco, N, Ruiz, N, Ricart, J, Lozada, A, Nani, S, Turri, D, Fernandez, H, Caruso, O, Zarandon, R, Bono, J, Arias, V, Allall, O, Marino, J, Cusimano, S, Schygiel, P, Buzetti, C, Penaloza, N, Berli, M, Worthley, S, Roach, A, Chew, D, Wright, T, Leitch, J, Hicks, E, Rankin, J, Venn-Edmonds, C, Lehman, R, Morrison, H, Shaw, J, Mak, V, Hii, C, Smith, K, Cross, D, Lilwall, L, Nelson, G, Loxton, A, Horowitz, J, Rose, J, Steinwender, C, Leisch, F, Kammler, J, Brussee, H, Zweiker, R, Niederl, E, Weihs, W, Giorgio, G, Lang, I, Drexel, H, Zanolin, D, Hoppe, U, Atzenhofer-Baumgartner, K, Pichler, M, Hainzer, D, Eber, B, Pichler, F, Foeger, B, Wechselberger, T, Mayr, H, Hofer, J, Stockenhuber, F, Warlits, B, Huber, K, Egger, F, Weidinger, F, Ziegler, B, Jirak, P, Metzler, B, Pachinger, O, Wanitschek, M, Auer, J, Grabscheit, G, Podczeck-Schweighofer, A, Priesnitz, T, Frank, H, El Allaf, D, Marechal, P, Roosen, J, Joly, E, Lefebvre, P, Arend, C, Sinnaeve, P, De Velder, L, Hellemans, S, Vanhauwaert, B, Van Dorpe, A, Heyse, A, Vantomme, C, Striekwold, H, Van Den Broeck, D, Lancellotti, P, Schoors, D, Lemoine, I, Taeymans, Y, De Wolf, L, Brike, C, Vercauteren, S, Tahon, S, Vervoort, G, Mestdagh, I, Pirenne, B, Cardinal, F, Lips, S, Dujardin, K, Debrouwer, K, Dhooghe, G, Holvoet, G, van de Borne, P, Renard, M, De Clippel, M, Lesseliers, H, Van Miert, N, Saraiva, J, Vicente, C, Rossi, P, Dos Santos LB, Duda, N, Tognon, Ap, Serrano, C, Gomes, Fl, Manenti, Er, Silveira, Ds, Maia, L, Mouco, Om, Paiva, M, Antonangelo, A, de Souza, J, Lino, Ea, Leães, P, Blacher, Mg, Kormann, A, Ultramari, Ft, Dutra, O, Mendelski, Am, Morgado, S, Ardito, W, Greque, G, Ardito, Rv, Pimentel Filho, P, Zucchetti, C, Alves, A, Seabra, Am, Mattos, M, Miranda, Lf, Silva, D, Uehara, Rm, Marin Neto, J, Schmidt, A, Braga, J, Rodrigues, A, Abrantes, J, Pinheiro, L, Bodanese, L, Magedanz, Éh, Piegas, L, Dos Santos ES, Wainstein, M, Ribeiro, J, Stein, R, Marino, R, Machado, Vm, Moraes Junior, J, Guimarães, S, da Costa FA, Ferraz, Rf, Albuquerque, D, Rocha, Rm, de Carvalho Moreira, R, Dohmann, H, Costantini, C, Tarastchuk, Jc, Coelho, O, Cirillo, W, Sousa, A, Almeira, As, Stefanini, E, Silva, F, Teixeira, M, da Cunha, C, Précoma, D, Facchi, Tl, Rupka, D, Thiessen, S, Warnica, J, Smith, B, Della Siega, A, Klinke, P, Nelson, S, Dion, D, Gilbert, N, Hui, W, Kvill, L, Sussex, B, Luther, A, Dupuis, R, Ouimet, F, Pandey, A, Clarus, S, Senaratne, M, Ferdinandis, H, Mukherjee, A, Bozek, B, Vizel, S, Markov, G, Zimmermann, R, Stephens, W, Tremblay, B, Wong, G, Uchida, N, Brossoit, R, Peck, C, Van Kieu, C, Forgione, M, Bata, I, Cossett, J, Kostuk, W, Arnold, M, Bone, C, Grondin, F, Bilodeau, N, Gosselin, G, David, M, Giannoccaro, J, Beresford, P, Polasek, P, Roberts, P, Doucet, M, Beaudry, M, Cheung, S, Cleveland, T, Bhargava, R, Mccallum, A, Ma, P, Morrissette, J, Cleveland, D, Chadwyn, D, Nigro, F, Weeks, A, Cryderman, C, Leader, R, Houde, G, Rousseau, S, Pearce, M, Radyk, M, Lonn, E, Magi, A, Lefkowitz, C, Sandrin, F, Coffin, N, Lubelsky, B, Coldwell, J, Habot, J, Mcpherson, C, De Larochelliere, R, Roy, M, Haichin, R, Barber, C, Bhesania, T, Kitagawa, H, To, T, Donnelly, B, Tymchak, W, Harris, L, Kouz, S, Huynh, T, St Jacques, B, Lamy, A, Rizzo, A, Stein, J, Childs, C, Wong, B, Poirier, R, Gupta, M, Dela Cruz, C, Constance, C, Gauthier, M, Ervin, F, Ouellette, M, Kokis, A, Lemay, C, Kwok, K, Leung, C, Lee, D, Nesmith, J, Renton, J, Syan, G, Turek, M, Hogan, D, Griffin, P, Lipson, A, Winestock, J, Abramson, B, Fogel, A, Gagne, C, Bergeron, J, Clarke, A, Slipp, S, Darcel, I, Carling-Chambers, L, Kannampuzha, P, Pallie, S, Krekorian, S, Vertes, G, Roth, S, Lai, K, Heath, J, Perez, L, Arriagada, G, Castro, P, Villa, F, Rodríguez, M, Ramos, G, Baraona, F, Núñez, A, García, M, Jofre, C, Silva, P, Lamich, R, 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Sabatine, M., Marti, J., Perlman, R., Pavlides, A., Joffe, I., Albirini, A., Campbell, T., Puri, S., Lopez, C., Pearce, D., Shah, D., McPherson, J., Donegan, R., Murdock, D., Block, D., Malik, A., Musina, R., Dauber, I., Varner, C., Bach, R., Palazzolo, M., Bhalla, H., Thompson, M., Pollock, S., Johnson, S., Lipson, L., Brunk, S., Karas, S., Vicari, R., Kuvin, J., Mooney, P., Aycock, G., Lane, B., Sharma, M., Gibson, T., Chang, G., DiVito, P., Mehta, R., Watkins, K., Chiu, A., Gunderson, J., Tedder, B., Williams, P., Hage-Korban, E., Childs, A., Banerjee, S., Kazi, F., Bennett, J., Barnes, D., Wohns, D., Noorman, C., Aggarwal, K., Lau-Sickman, A., Paulowski, J., Amos, M., Rider, J., Fenton, S., Schantz, M., Hakas, J., Mcsorley, J., Felten, W., Bitzer, V., Russell, J., Loyo, J., Adjei, A., Mehta, K., Uretsky, B., Hale, M., Shaikh, S., Miller, M., Hollenbaugh, D., Crawford, K., Fortuin, D., Galindo, A., Del Core, M., Butkus, E., Collins, J., Prior, J., Hahn, R., Greene-Nashold, J., Alexander, J., Genova, E., MacDonell, A., Broadwater, S., Kereiakes, D., White, D., Lopez, M., Schenks, R., Lui, H., Gibbons, P., Davis, B., Thornton, K., Daley, P., Budzon, S., McCullum, K., Delio-Cox, B., Nadar, V., Keim, S., McLaurin, B., Davis, C., Betzu, R., Al-Jumaily, J., Bolli, R., Alshaher, M., Leesar, M., Collins, T., Akkad, H., Bilazarian, S., Marsters, M., Kennett, J., Melegrito, K., Mostel, E., Harris, R., Chang, M., Hatfield, G., Makam, S., Garvey, M., Levite, H., White, J., Abdel-Latief, A., Pelletier, L., Carr, K., Mckenna, K., De Lemos, J., Soto, G., Kozina, J., Harris, D., Vlastaris, A., Bittel, B., Riba, A., Gugudis, J., Singh, N., Qureshi, I., Doty, W., Lehmann, J., Lieber, I., Martin, S., Nicu, M., Bhalodkar, N., Ravi, P., Canto, J., Bass, M., Campbell, C., Steinhubl, S., Moles, K., Harjai, K., Stapleton, D.D., Hoey, K., Erwin, J., Fikes, W., Stein, B., Sabatino, K., Teklinski, A., Colfer, H., Ward, P., Langevin, E., Faucett, S., Mamdani, S., DeSimone, L., Tuohy, E., Cullen, T., Eisenberg, S., Chronos, N., Allen, R.P., Erickson, B., Mahon, K., Kirby, A., Siegel, C., Stroud, L., Johnson, J., Panchal, V., Pearson, A., Abell, T., De Gregorio, M., Boomer, L., Vahdat, O., VanNatta, B., Long, P., Chalavarya, G., Skatrud, L., Carey, C., Wright, W., Mechem, C., Matthews, B., Adams, A., Vora, K., Wead, J., Koren, M., Gregory, D., El Khadra, M., Peacock, G., Kieval, J., Barron, M., Lewis, D., Grice, R., Bobek, M., Moore, C., Nygaard, T., Fischell, T., Salman, W., Schneider, C., Muhlestein, B., Peeler, D., Chang, D., Todd, A., Chilakamarri, V., Hanley, P., Gelormini, J., Iacona, M.A., Effron, B., Mazzurco, S., Mazzella, M., Wyman, P., Orchard, R., Battin, D., Rezkalla, S., Bishop, C., Sharp, S., Gredler, F., Knap, P., Fadel, M., Saucedo, J., Keng, A., Imburgia, M., Blank, E., Effat, M., Khoury, S., Mardis, R., Baldari, D., Tafuri, L., Mascolo, R., Taylor, D., Mandviwala, M., Khan, W., Mumford, T., Mayer, N., Mitchell, B., Oliver, T., Lombardi, W., Zimmerman, T., Rohrbeck, S., Cooke, L., Craig, M., Mego, D., Griffin, B., Perez, J., LeClerc, K., Addington, J., Aboufakher, R., Ahmed, A., Westecott, B., Steel, K., Hawkins, K., Shah, A., Ward, U., McGreevy, M., Goldberg, R., Prashad, R., McDonough, C., Silver, K., Josephson, R., Witsaman, S., Labib, S., Woodhead, G., Schrank, J., Bell, K., Chandna, H., Holly, D., Bethea, C., Fife, B., Gruberg, L., Singer, A., Ramgadoo, M., Lalonde, T., Morin, R., French, W., Barillas, O., Gradner, G., Kahn, Z., Gress, J., Rocco, D., Thew, S., Stifter, W., Fisher, M., McNamara, J., Kupfer, J., Agocha, A., Cush, S., Jones, S., Whitaker, T., Stover, T., Kumkumian, G., Kent, K., Greenberg, A., Pandey, P., Pytlewski, G., Matsumura, M., Kai, W., Sameshima, S., Thomas, J., MacNicholas, D., Pillai, K., Jones, D., Navas, J.P., Laskoe, B., Patel, P., Fini, G., Minor, S., Shipwash, T., Cabrera-Santamaria, A., Rivera, E., Mincher, L., Jafar, M., Yen, M., Finkle, C., Rahimtoola, A., Severson, L., Labroo, A., Jinich, D., Tam, K., Vogel, C., Aggarwal, R., Zakhary, B., Curtis, S., Lyster, M., Humphrey, K., Lavine, P., Fujise, K., Birnbaum, Y., Allen, J., Kesselbrenner, M., Michel, K., Staniloae, C., Liu, M., Sonel, A., Macioce-Caffas, A., Amidon, T., Leggett, J., Yedinak, S., Gudmundsson, G., Sabharwal, J., Dagefoerde, N., Wu, W., Meyerrose, G., Roongsritong, C., Jenkins, L., Lieberman, S., Sokol, S., Gutierrez, C., Nelson, C., Barrett, J., Hotchkiss, D., Farley, A., Atassi, K., Christy, L., Baig, M., Di Fazio, J., Meengs, M., Thomas, K., Surmitis, J., DeVault, S., Farhat, N., Hulyalkar, A., Riddell, L., Rivera, W., Sheynberg, B., Kobayashi, J., Katsaropoulos, J., Jan, M., Krucoff, M., Paterno, C., Chandrasekaran, S., Curry, R., Cassavar, D., Wheeler, M., McGarvey, J., Schwarz, L., Miller, E., Andrea, B., Carswell, B.S., Lurie, M., Patti, J., Bowden, W., Vasiliauskas, T., Latham, R., Schwartz, B., Bradford, L., Mattleman, S., Wertheimer, J., Goulden, D., Khan, M., Hawkins, B., Ostfeld, R., Mueller, H., Ash, Y., Wilson, V., Bayer, M., Marshall, J., Dobies, D., Dawson, G., Osman, A., Saba, F., Costello, T., Fuentes, F., Underwood, C., Vijay, N., Washam, M., Dietz, W., Glasgow, B., Mukherjee, S., Hinchion, N., Speirs, S., Thornley, A., Lee, K., Movahed, M., Strootman, D., Chernick, R., Parrott, C., Flock, C., Marques, V., Syzmanski, E., Rama, P., Domingo, D., Wu, L., Bauer, B., Dionisopoulos, P., Aggarwal, A., Holcomb, R., Foster, R., Hancock, T., Hargrove, J., Fletcher, A., Stine, R., Bullivant, M., Adams, K., Lohman, J., Klepper, V., Kabour, A., Neidhardt, J., Phillips, W., Tardiff, S., Aji, J., Corut, S., Foster, G., Firek, C., St Goar, F., Sumner, R., Davis, T., Schneider, R., Schneider, W., Villa, A., Desai, V., Chhabra, A., Banks, K., Herzog, W., Burley, T., Quyyumi, A., Smiley, W., Manocha, P., Fishbein, G., Weller, C., Coffman, A., Kim, C., Kedia, A., Firth, B., Rizvi, M., Dahiya, R., Foster, B., Balcells, E., Metzger, D.C., Lester, J., Bissett, J., Fahdi, I., Sides, E.A., Azrin, M., Martin, C., Quick, A., Conaway, D., Garg, M., Schallert, G., Lancaster, L., Mckissick, S., Atieh, M., Garbarino, J., Eisenberg, D., Uusinarkaus, K., Wirtemburg, P., Ellis, J., Cristaldi, J., Berglund, R., Negus, B., Pappas, J., Rocha, R., Nguyen, T., Stone, J., Janosik, D., Labovitz, A., Elmore, N., Dave, R., Loffredo, K., Gabriel, G., Snyder, C., Ahmed, O., Stone, H., Kelley, M., Diffenback, M., Friedman, B., Zirkle, J., Severa, L., Sample, S., Dignen, K., Raisinghani, A., Ben-Yehuda, O., Ghannadian, B., Moscoso, R., Mankowski, J., Boliek, W., Rukavina, M., Davis, W., Ledbetter, S., Handel, F., Mastouri, R., Mahenthiran, J., Foltz, J., Malhotra, V., Jonas, J., Berk, M., Singh, V., Nelson, M., Elsner, G., Gall, J., Kondo, N., Frank, S., Chandraratna, P., Ranasinghe, S., Ebrahimi, R., Treadwell, M., Walters, B., Hughes, L., Kramer, J., Kumar, K., Mente, T., Lachterman, B., Schifferdecker, B., Munshi, K., Sease, D., Waldo, D., Chandler, G., Manns, D., Nahhas, A., Kamalesh, M., Williams, V., Reich, D., Desalca, M., Sharma, S., Liston, M., Gupta, K., Costa, M., Altschuller, A., Lemmertz, K., Shanes, J., Hansen, C., Therrien, M., Mendelson, R., Ramnarine, R., Myers, G., Donovan, C., Klein, M., Fine, D., Owens, S., Murray, C., Ketroser, R., Heifetz, S., Darnell, Z., Touchon, R., Taghizadeh, B., Bohle, D., Norwood, D., Forrest, T., Jackson, S., Shumate, K., Bayles, A., Masroor, M., North, W.K., Fishberg, R., Merveil-Ceneus, B., Butcher, R., Menapace, F., Kilbride, S., Ramabadran, R.S., Loukinen, K., Khalil, J., Ramabadran, R., Walsh, S., Gill, S., Cyncar, R., McLachlan, J., Surakanti, V., Rusterholtz, L., Shoukfeh, F., Stephenson, L., Tsang, M., Nolan, V., Gilchrist, I., Jefferson, D., Feldman, T., Reyes, L., Santos, R., Little, W., Wesley, D., Gharib, W., Mendell, A., Esham, G., Kakavas, P., Whitcomb, C., Book, K., Bazzi, A., Alvarez, J., Cohen, Y., Ayres, T., Rhule, V., Labib, A., Schuler, P., Zughaib, M., Telck, K., Bikkina, M., Turnbull, K., Sharma, T., Orosz, S., Shah, R., Petrino, M., Hughes, M., Hershey, J., Hudock, D., Hui, P., Von Bakonyi, A., Arnold, A., Kappel, D., Pennock, G., Cloud, B., Tucker, K., Harp, L., Hoover, C., Eisenhauer, M., Roth, J., Young, C., Thai, H., Escalante, A., Bautista, J., Gazmuri, R., Nyland, J., Cubeddu, L., DeFranco, A., Dias, D., Fielding, M., Reeves, R., Hermany, P., Meissner-Dengler, S., Evans, M., Flores, E., Tannenbaum, A., McGarr, K., Moran, J., Stout, E., Allred, S., Henderson, D., Crandall, L., Strote, J., Voyles, W., Robeson, D., Bedoya, R., Omar, B., Pettyjohn, F., Revere, C., Coy, K., Margolis, J., Sotolongo, C., Scheffel, M., Munir, A., Shirwany, A., Douglas, L., Girala, R., Humphreys, R., Agarwal, J., Bankowski, D., Watson, R., Bishop, B., Klementowicz, P., Blais, D., Cohen, B., Lobur, E., Dimenna, J., Dempsey, K., Izzo, M., Bondi, L., Carell, E., Eaton, C., Saltiel, F., Grewal, G., Connolly, T., Little, T., Wiegman, P., Gips, S., Held, J., Paraschos, A., Quesada, R., Goudreau, E., Sears, M., Istfan, P., Holt, S., McClung, J., Nguyen, N., Quintana, O., Gottlieb, D., Knutson, T., Barringhaus, K., Lester, F., Sullivan, P., Rodriguez-Ospina, L., Cannon, Cp, Blazing, Ma, Giugliano, Rp, Mccagg, A, White, Ja, Theroux, P, Darius, H, Lewis, B, Ophuis, To, Jukema, Jw, De Ferrari, Gm, Ruzyllo, W, De Lucca, P, Im, K, Bohula, Ea, Reist, C, Wiviott, Sd, Tershakovec, Am, Musliner, Ta, Braunwald, E, Califf, Rm, for the IMPROVE-IT, Investigator, Cianflone, D, Cardiovascular Division (SZG), Brigham and Women's Hospital [Boston], College of Information Science and Engineering, Ritsumeikan University, Montreal Heart Institute (MONTREAL HEART INSTITUTE), Laboratoire des Micro-algues toxiques, Institut Louis Malardé [Papeete] (ILM), Institut de Recherche pour le Développement (IRD)-Institut de Recherche pour le Développement (IRD), Interuniversity Cardiology Institute Netherlands, Institute of Cardiology (WARSAW - Cardiology), Institute of Cardiology, Merck Sharp & Dohme Corp., Merck & Co. Inc, DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, Facolta' di MEDICINA e CHIRURGIA, AREA MIN. 06 - Scienze mediche, Cannon, C.P., Blazing, M.A., Giugliano, R.P., Mccagg, A., White, J.A., Lewis, B.S., Jukema, J.W., De Lucca, P., Im, K., Bohula, E.A., Reist, C., Wiviott, S.D., Tershakovec, A.M., Musliner, T.A., Braunwald, E., Califf, R.M., for the IMPROVE-IT Investigators [.., C. Rapezzi, ], Other departments, Cannon, Christopher P, Blazing, Michael A., Giugliano, Robert P., Mccagg, Amy, White, Jennifer A., Theroux, Pierre, Darius, Harald, Lewis, Basil S., Ophuis, Ton Oude, Jukema, J. Wouter, De Ferrari, Gaetano M., Ruzyllo, Witold, De Lucca, Paul, Kyungah, Im, Bohula, Erin A., Reist, Craig, Wiviott, Stephen D., Tershakovec, Andrew M., Musliner, Thomas A., Braunwald, Eugene, and Califf, Robert M.

Subjects
Male, Simvastatin, acute coronary syndrome, aged, anticholesteremic agents, azetidines, cardiovascular diseases, cholesterol, ldl, double-blind method, drug therapy, combination, ezetimibe, female, humans, hydroxymethylglutaryl-coa reductase inhibitors, kaplan-meier estimate, male, middle aged, simvastatin, triglycerides, medicine (all, [SDV]Life Sciences [q-bio], Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Bococizumab, Triglyceride, chemistry.chemical_compound, 0302 clinical medicine, Azetidine, Cardiovascular Disease, Anticholesteremic Agent, Acute Coronary Syndrome, Aged, Anticholesteremic Agents, Azetidines, Cardiovascular Diseases, Cholesterol, LDL, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Middle Aged, Triglycerides, 030212 general & internal medicine, Medicine (all), Research Support, Non-U.S. Gov't, Hazard ratio, General Medicine, Acute Coronary Syndrome, Aged, Anticholesteremic Agents, Azetidines, Cardiovascular Diseases, Ezetimibe, Female, Humans, Male, Middle Aged, 3. Good health, Multicenter Study, Editorial, Cholesterol, Randomized Controlled Trial, Combination, Ezetimibe, lipids (amino acids, peptides, and proteins), Human, medicine.drug, medicine.medical_specialty, Acute Coronary Syndroms, Urology, Acute Coronary Syndrome/drug therapy, Anticholesteremic Agents/adverse effects, Anticholesteremic Agents/therapeutic use, Azetidines/adverse effects, Azetidines/therapeutic use, Cardiovascular Diseases/epidemiology, Cardiovascular Diseases/mortality, Cardiovascular Diseases/prevention & control, Cholesterol, LDL/blood, Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Simvastatin/therapeutic use, Triglycerides/blood, NO, LDL, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Drug Therapy, Internal medicine, Journal Article, medicine, Comparative Study, Alirocumab, business.industry, PCSK9, ta3121, Lomitapide, DOENÇAS CARDIOVASCULARES, Endocrinology, chemistry, Statin Therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitor, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known.METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years.RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (PCONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.).

Published
2015
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22. Abstract P6-03-05: Dual HER2 blockade of an activating driver HER3 mutation: A proof of principle study in a metastatic breast cancer patient

Author

Bidard, Francois-Clement, primary, Ng, Ck, additional, Tulukcuoglu, Ezgi, additional, Piscuoglio, S, additional, Descroix, Stephanie, additional, Mignot, Laurent, additional, Viovy, Jean-Louis, additional, Cottu, Paul, additional, Sigal, Brigitte, additional, Vincent-Salomon, Anne, additional, Weigelt, Britta, additional, Pierga, Jean-Yves, additional, and Reis-Filho, Jorge, additional

Published
2015
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24. Ischemic mitral valve repair surgery due to inferior wall infarction

Author

J Nesser, Ng Ck, Hartl P, H Auer, Pachinger O, and C Punzengruber

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Mitral valve repair, business.industry, medicine.medical_treatment, Infarction, medicine.disease, Surgery, Internal medicine, Cardiology, Inferior wall, Medicine, Cardiology and Cardiovascular Medicine, business
Published
2004
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25. Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes

Author

McBride, DJ, Etemadmoghadam, D, Cooke, SL, Alsop, K, George, J, Butler, A, Cho, J, Galappaththige, D, Greenman, C, Howarth, KD, Lau, KW, Ng, CK, Raine, K, Teague, J, Wedge, DC, Caubit, X, Stratton, MR, Brenton, JD, Campbell, PJ, Futreal, PA, Bowtell, DDL, McBride, DJ, Etemadmoghadam, D, Cooke, SL, Alsop, K, George, J, Butler, A, Cho, J, Galappaththige, D, Greenman, C, Howarth, KD, Lau, KW, Ng, CK, Raine, K, Teague, J, Wedge, DC, Caubit, X, Stratton, MR, Brenton, JD, Campbell, PJ, Futreal, PA, and Bowtell, DDL

Abstract

The application of paired-end next generation sequencing approaches has made it possible to systematically characterize rearrangements of the cancer genome to base-pair level. Utilizing this approach, we report the first detailed analysis of ovarian cancer rearrangements, comparing high-grade serous and clear cell cancers, and these histotypes with other solid cancers. Somatic rearrangements were systematically characterized in eight high-grade serous and five clear cell ovarian cancer genomes and we report here the identification of > 600 somatic rearrangements. Recurrent rearrangements of the transcriptional regulator gene, TSHZ3, were found in three of eight serous cases. Comparison to breast, pancreatic and prostate cancer genomes revealed that a subset of ovarian cancers share a marked tandem duplication phenotype with triple-negative breast cancers. The tandem duplication phenotype was not linked to BRCA1/2 mutation, suggesting that other common mechanisms or carcinogenic exposures are operative. High-grade serous cancers arising in women with germline BRCA1 or BRCA2 mutation showed a high frequency of small chromosomal deletions. These findings indicate that BRCA1/2 germline mutation may contribute to widespread structural change and that other undefined mechanism(s), which are potentially shared with triple-negative breast cancer, promote tandem chromosomal duplications that sculpt the ovarian cancer genome.

Published
2012

28. Clinical presentation of rupture of the left-ventricular free wall after myocardial infarction: report of five cases with successful surgical repair

Author

C. Schwarz, Pachinger O, Ng Ck, C Punzengruber, Schauer N, and Hartl P

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Chest Pain, medicine.medical_treatment, Hemopericardium, Myocardial rupture, Pericardial effusion, Severity of Illness Index, Pericardial Effusion, Syncope, Pseudoaneurysm, Cardiac tamponade, Cause of Death, medicine, Humans, Myocardial infarction, Aged, Heart Rupture, Post-Infarction, Ultrasonography, Heart Failure, business.industry, Suture Techniques, Mitral valve replacement, Electrocardiography in myocardial infarction, Middle Aged, medicine.disease, Surgery, Cardiac Tamponade, Treatment Outcome, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract

Rupture of the left-ventricular free wall may not always result in immediate irreversible hemodynamic collapse. We report a series of five patients (4 male, 1 female; age 59-79 years) successfully operated for postinfarction free-wall rupture with good long-term results. Two patients presented with syncopy and acute tamponade three days after an acute myocardial infarction. In two patients with atypical chest pain and congestive heart failure, a large pericardial effusion and an extreme localized thinning of a myocardial scar region was seen several weeks after an uncomplicated myocardial infarct. In one patient a pseudoaneurysm was detected, which developed asymptomatically within three weeks after a posterior myocardial infarct. In all cases myocardial rupture was suspected after an echocardiographic examination. At surgery a hemopericardium and a localized rupture site were found. The surgical procedure included closure of the defect by direct suture or patch, CABG in 3 cases, and mitral valve replacement in one patient. The postoperative course was uneventful, only one patient needed IABP for 24 hours. Three patients returned to NYHA functional class I, one patient to class II, and one patient to class III. The latter patient died of heart failure 17 months postoperatively, and the other patients are still alive 4,18,24, and 26 months postoperatively. Thus clinical representation of left-ventricular free-wall rupture after myocardial infarction can be highly variable. But close cooperation between experienced echocardiographers and surgeons may allow successful corrections with good long term-results.

Published
1996

29. A New Flexible Periphery Sensor for Noninvasive and Mobile Respiration Sensing for Medical Diagnosis

Author

Gao, YS, Tse, SF, NG, CK, Ho, MS, Au, HW, Gao, YS, Tse, SF, NG, CK, Ho, MS, and Au, HW

Abstract

A novel noninvasive flexible periphery sensor for respiration detection has been developed. At low cost, it is lightweight and portable and is able to fit to human body without affecting user movement, suitable for different applications under various conditions. Real time data of a breathing profile provided by the sensor can be recorded and it is very useful for medical diagnosis. The working principle of the proposed sensor is presented and the developed prototype is described. Experimental testing of the sensor with different proposed materials has been performed. It was found that the sensor with carbon conductive grease that contains pure carbon black and dimethylpolysiloxane can extend approximately 10%. The change in voltage for the extension was 0.7V. The repeatability was +/-7.6% FS and the response time is less than 1s. The results demonstrate the feasibility of the proposed sensor for diagnosis of pulmonary disease.

Published
2004

32. Clinical and economic impact of an antibiotics stewardship programme in a regional hospital in Hong Kong.

Author

Ng CK, Wu TC, Chan WM, Leung YS, Li CK, Tsang DN, and Leung GM

Abstract

BACKGROUND: Inappropriate use of antibiotics is one of the important factors attributing to emergence of drug-resistant pathogens. Infection with multidrug-resistant pathogens adversely affects quality of medical care. CONTEXT: Queen Elizabeth Hospital, an 1800-bed acute service hospital in Hong Kong. Antibiotics are commonly prescribed for treating acute infections. KEY MEASURES FOR IMPROVEMENT: Reduce inappropriate prescription of broad-spectrum antibiotics and overall antibiotic prescription through implementation of a multidisciplinary antibiotics stewardship programme (ASP). STRATEGIES FOR CHANGE: A multidisciplinary programme involving policy and guideline formulation, education and feedback, monthly antibiotic consumption and cost monitoring, antimicrobial susceptibility pattern reporting and concurrent feedbacks for commonly prescribed broad-spectrum antibiotics was implemented in 2004. Predefined logistics to prescribe 'restricted' antibiotics were formulated and implemented with collaborative efforts from clinical and non-clinical departments. The programme was supported by management at department and hospital levels. EFFECTS OF CHANGE: Broad-spectrum antibiotics were prescribed inappropriately in 28.9% (n = 192) clinical scenarios. The ASP reduced the restricted and total antibiotic consumption as well as the antibiotics-related costs. Predefined clinical outcomes were not adversely affected. Economic analysis suggested that the extra human cost in running ASP could be offset by savings from antibiotic expenditure. LESSONS LEARNED: It is cost-effective to implement a multidisciplinary ASP in acute service hospitals as the programme reduces antibiotic consumption and results in overall cost savings. The quality of medical care is not jeopardized as the important clinical outcomes are not adversely affected. The generalisability and sustainability of ASPs in other clinical contexts warrant further studies to ensure the continuous success of this programme. [ABSTRACT FROM AUTHOR]

Published
2008
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34. High-dose pulse versus nonpulse corticosteroid regimens in severe acute respiratory syndrome.

Author

Ho JC, Ooi GC, Mok TY, Chan JW, Hung I, Lam B, Wong PC, Li PC, Ho PL, Lam WK, Ng CK, Ip MS, Lai KN, Chan-Yeung M, and Tsang KW

Abstract

The treatment of atypical pneumonia, subsequently termed severe acute respiratory syndrome (SARS), is controversial, and the efficacy of corticosteroid therapy is unknown. We have evaluated the clinical and radiographic outcomes of 72 patients with probable SARS (median age 37 years, 30 M), who received ribavirin and different steroid regimens in two regional hospitals. Chest radiographs were scored according to the percentage of lung field involved. Seventeen patients initially received pulse steroid (PS) (methylprednisolone > or =500 mg/day) and 55 patients initially received nonpulse steroid (NPS) (methylprednisolone <500 mg/day) therapy. The cumulative steroid dosage; intensive care unit admission, mechanical ventilation, and mortality rates; and hematologic and biochemical parameters were similar in both groups after 21 days. However, patients in the PS group had less oxygen requirement, better radiographic outcome, and less likelihood of requiring rescue PS therapy than their counterparts. There was no significant difference between the two groups in hemolytic anemia, severe secondary infections, or hematemesis, but patients in the PS group had less hyperglycaemia. Initial use of pulse methylprednisolone therapy appears to be a more efficacious and an equally safe steroid regimen when compared with regimens with lower dosage and should be considered as the preferred steroid regimen in the treatment of SARS, pending data from future randomized controlled trials. [ABSTRACT FROM AUTHOR]

Published
2003

36. Regional brain metabolic correlates of alpha-methylparatyrosine-induced depressive symptoms: implications for the neural circuitry of depression.

Author

Bremmer JD, Vythilingam M, Ng CK, Vermetten E, Nazeer A, Oren DA, Berman RM, Charney DS, Bremner, J Douglas, Vythilingam, Meena, Ng, Chin K, Vermetten, Eric, Nazeer, Ahsan, Oren, Dan A, Berman, Robert M, and Charney, Dennis S

Abstract

Context: We previously used positron emission tomography (PET) measurement of brain metabolism with 18fluorodeoxyglucose to show that patients receiving selective serotonin reuptake inhibitors (SSRIs) who have a tryptophan depletion-induced return of depressive symptoms have an acute decrease in metabolism in orbitofrontal cortex, dorsolateral prefrontal cortex, and thalamus. Many patients with depression in remission while taking norepinephrine reuptake inhibitors (NRIs) (but not SSRIs) experience a return of depressive symptoms with depletion of norepinephrine and dopamine using alpha-methylparatyrosine (AMPT).Objective: To assess brain metabolic correlates of AMPT administration in patients with depression in remission while receiving NRIs.Design, Setting, and Participants: Randomized, controlled, double-blind trial in which 18 patients recruited in 1997-2000 from the general community who had depression in remission while taking NRIs had PET imaging in a psychiatric research unit following AMPT and placebo administration.Interventions: After initial medication with desipramine and follow-up until response, patients underwent active AMPT (five 1-g doses administered orally over 28 hours) and placebo (diphenhydramine hydrochloride, five 50- mg doses administered similarly) catecholamine depletion challenges in randomized order of assignment, after which PET imaging was performed on day 3 of each condition. Both study conditions were performed 1 week apart.Main Outcome Measures: Regional brain metabolism rates in patients with and without AMPT-induced return of depressive symptoms.Results: AMPT-induced return of depressive symptoms was experienced by 11 of the 18 patients and led to decreased brain metabolism in a number of cortical areas, with the greatest magnitude of effects in orbitofrontal (P =.002) and dorsolateral prefrontal (P =.03) cortex and thalamus (P =.006). Increased resting metabolism in prefrontal and limbic areas predicted vulnerability to return of depressive symptoms.Conclusions: Different neurochemical systems that mediate depression may have effects on a common brain circuitry. Baseline metabolism in successfully treated depressed patients may predict vulnerability to future episodes of depression. [ABSTRACT FROM AUTHOR]

Published
2003

40. Unstable angina early after aortic valve replacement surgery in a female patient with normal coronary arteries preoperatively--a case report.

Author

Gruber S, Ng CK, Schwarz C, Auer J, Gruber, Sybille, Ng, Choi-Keung, Schwarz, Christian, and Auer, Johann

Abstract

Background: Angina pectoris early after aortic valve replacement surgery in patients with previously normal coronary arteries may be life threatening and has to be assessed immediately.Case Report: 12 weeks after aortic valve replacement surgery, a 60-year-old female patient was referred for evaluation of recent onset of severe chest pain on mild exertion and at rest. Coronary angiography showed severe stenosis involving the left coronary ostium and the left main stem. The patient was urgently referred for bypass surgery and had an uneventful postoperative recovery.Conclusion: A high degree of suspicion is needed for early recognition and aggressive management of this rare but serious complication. [ABSTRACT FROM AUTHOR]

Published
2009
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42. Prediction model for short-term mortality after palliative radiotherapy for patients having advanced cancer: a cohort study from routine electronic medical data

Author

Chuk Kwan Ng, Hollis Luk, Aray Wong, Shing Fung Lee, Miguel Angel Luque-Fernandez, Frank Chi Sing Wong, [Lee,SF, Luk,H, Wong,A, Ng,CK, Wong,FCS] Department of Clinical Oncology, Tuen Mun Hospital, New Territories West Cluster, Hospital Authority, Hong Kong, Hong Kong. [Luque-Fernandez,MA] Department of Non-Communicable Disease and Cancer Epidemiology, Institute de Investigacion Biosanitaria de Granada (ibs.GRANADA), University of Granada, Granada, Spain. [Luque-Fernandez,MA] Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK., and There was no explicit funding for the development of this project. MALF is supported by a Miguel Servet I Investigator Award (grant CP17/00206 EU-FEDER) from the National Institute of Health, Carlos III (ISCIII), Madrid, Spain. His funders had no role in the study design, data collection, dataanalysis, data interpretation, or writing of the report.

Subjects
Male, medicine.medical_treatment, lcsh:Medicine, Logistic regression, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Patient Care::Palliative Care [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, 0302 clinical medicine, Palliative radiotherapy, Risk Factors, Neoplasms, Odds Ratio, Electronic Health Records, 030212 general & internal medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Odds Ratio [Medical Subject Headings], lcsh:Science, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Cancer, Multidisciplinary, Palliative Care, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, Prognosis, Cuidados paliativos, Neoplasias, Oncology, Outcomes research, 030220 oncology & carcinogenesis, Female, Cohort study, medicine.medical_specialty, Estudios de cohortes, Check Tags::Male [Medical Subject Headings], Article, 03 medical and health sciences, Radioterapia, Prediction model, Internal medicine, medicine, Humans, Mortality, Lung cancer, Aged, Radiotherapy, business.industry, lcsh:R, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Odds ratio, medicine.disease, Confidence interval, Radiation therapy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Records as Topic::Medical Records::Medical Records Systems, Computerized::Electronic Health Records [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Mortalidad, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], lcsh:Q, business
Abstract

We developed a predictive score system for 30-day mortality after palliative radiotherapy by using predictors from routine electronic medical record. Patients with metastatic cancer receiving first course palliative radiotherapy from 1 July, 2007 to 31 December, 2017 were identified. 30-day mortality odds ratios and probabilities of the death predictive score were obtained using multivariable logistic regression model. Overall, 5,795 patients participated. Median follow-up was 39.6 months (range, 24.5–69.3) for all surviving patients. 5,290 patients died over a median 110 days, of whom 995 (17.2%) died within 30 days of radiotherapy commencement. The most important mortality predictors were primary lung cancer (odds ratio: 1.73, 95% confidence interval: 1.47–2.04) and log peripheral blood neutrophil lymphocyte ratio (odds ratio: 1.71, 95% confidence interval: 1.52–1.92). The developed predictive scoring system had 10 predictor variables and 20 points. The cross-validated area under curve was 0.81 (95% confidence interval: 0.79–0.82). The calibration suggested a reasonably good fit for the model (likelihood-ratio statistic: 2.81, P = 0.094), providing an accurate prediction for almost all 30-day mortality probabilities. The predictive scoring system accurately predicted 30-day mortality among patients with stage IV cancer. Oncologists may use this to tailor palliative therapy for patients.

Published
2020
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44. Differentiation Between Responders and Non-Responders to Antibiotic Treatment in Mice Using 18 F-Fluorodeoxysorbitol/PET.

Author

Li J, Zheng H, Olson J, Warawa JM, and Ng CK

Subjects
Animals, Female, Mice, Treatment Outcome, Ribitol analogs & derivatives, Ribitol pharmacology, Ribitol therapeutic use, Sorbitol analogs & derivatives, Sorbitol pharmacology, Klebsiella pneumoniae drug effects, Bacterial Infections drug therapy, Bacterial Infections diagnostic imaging, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Positron-Emission Tomography, Mice, Inbred C57BL, Fluorodeoxyglucose F18 chemistry
Abstract

Purpose: Bacterial infection causes significant mortality and morbidity worldwide despite the availability of antibiotics. Differentiation between responders and non-responders early on during antibiotic treatment will be informative to patients and healthcare providers. Our objective was to investigate whether PET imaging with 18 F-Fluorodeoxysorbitol ( 18 F-FDS) or 18 F-FDG can be used to differentiate responders from non-responders to antibiotic treatment., Procedures: NTUH-K2044 was used for infection in Albino C57 female mice. Each mouse was inoculated intratracheally with NTUH-K2044 to induce lung infection (n = 8). For treatment studies, two bacterial doses for animal inoculation and two treatment starting times were compared to optimize treatment profiles. 18 F-FDS or 8 F-FDG /PET imaging was performed to monitor treatment progression., Results: Our results demonstrated that the treatment profiles for mice infected with 25 CFU hvKp and antibiotic treatment starting at 24 p.i. were not ideal due to no evidence of lung infection and lack of treatment efficacy. The optimal scheme is to use 250 CUF for infection and start antibiotic treatment at 24 h p.i. to monitor antimicrobial efficacy. 75% of the mice were classified as responders to antibiotic treatment. 25% of the mice were classified as non-responders. 18 F-FDG was used to compare with 18 F-FDS, but all mice showed increased lung uptake of 18 F-FDG during 3-day treatments., Conclusions: 18 F-FDS is a promising PET tracer to image bacterial infection. It can be used to monitor response to treatment, and differentiate responders from non-responders to antibiotic treatment, but 18 F-FDG cannot, probably due to the presence of high degree of inflammation before and after treatment., Competing Interests: Declarations. Conflict of Interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Published
2024
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45. Development and validation of the mobile adherence satisfaction scale (MASS) for medication adherence apps.

Author

Rana R, Ibrahim BB, Huri HBZ, Wahab IBA, Govindaraju K, Shukeri MSM, Ng CK, and Ong SC

Subjects
Humans, Female, Male, Middle Aged, Aged, Surveys and Questionnaires standards, Pilot Projects, Telemedicine, Reproducibility of Results, Factor Analysis, Statistical, Delphi Technique, Medication Adherence, Mobile Applications, Patient Satisfaction
Abstract

Objective: To develop and validate the Mobile Adherence Satisfaction Scale (MASS) for assessing user satisfaction with mobile health applications aimed to improve medication adherence., Methods: The study involved patients over 18 with asthma, hypertension, heart failure, or diabetes, who used the CareAide® app for six months. Scale development included a literature review, expert consultations, and patient interviews, initially identifying 129 items. These were refined to 27 using a two-round Delphi technique and grouped into six dimensions: user interface, perceived usability, system quality, service quality, feature satisfaction, and general satisfaction. A pilot study with 30 participants further refined the model, which was then validated with 135 participants using exploratory and confirmatory factor analyses in SPSS 29 and SmartPLS 4. Data were collected via self-administered questionnaires., Results: A total of 135 complete questionnaires were analysed. Respondents had an average age of 66.7 years (SD = 11.6) with 42.2 % male (n = 57) and 57.8 % female (n = 78). After removal of an item due to cross loading, exploratory factor analysis resulted six dimensions and 26 items with Kaiser-Meyer-Olkin measure of 0.837 and Bartlett's Test of Sphericity (χ 2 (n = 325) = 2085.673, P < 0.001). The confirmatory factor analysis confirmed high reliability and validity: Cronbach's alpha values > 0.70 for each dimension and an overall alpha of 0.89, with Composite Reliability and Average Variance Extracted both >0.70 and >0.50, respectively, for each dimension. Structural model indicated a significant positive impact of user interface (β = 0.226, P = 0.006) and feature satisfaction (β = 0.230, P = 0.002) on general satisfaction, explaining 23.1 % of the variance (R 2  = 0.231)., Conclusion: The study developed and validated the MASS, a reliable tool for assessing user satisfaction with mHealth apps. User interface design and feature satisfaction are key for long-term engagement and consistent medication adherence., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Published
2024
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46. Tracing Tumor Heterogeneity of Pleomorphic Carcinoma of the Lung.

Author

Roma L, Ercan C, Conticelli F, Akyürek N, Savic Prince S, Mertz KD, Diebold J, Lardinois D, Piscuoglio S, Ng CK, and Bubendorf L

Subjects
Humans, Male, Female, Middle Aged, Aged, Genetic Heterogeneity, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung metabolism, Lung Neoplasms pathology, Lung Neoplasms genetics, Lung Neoplasms metabolism
Abstract

Introduction: Pulmonary pleomorphic carcinoma (PPC) is an aggressive and highly heterogeneous NSCLC whose underlying biology is still poorly understood., Methods: A total of 42 tumor areas from 20 patients with PPC were microdissected, including 39 primary tumors and three metastases, and the histologically distinct components were subjected to whole exome sequencing separately. We further performed in silico analysis of microdissected bulk RNA sequencing and methylation data of 28 samples from 14 patients with PPC. We validated our findings using immunohistochemistry., Results: The epithelial and the sarcomatoid components of PPCs shared a large number of genomic alterations. Most mutations in cancer driver genes were clonal and truncal between the two components of PPCs suggesting a common ancestor. The high number of alterations in the RTK-RAS pathway suggests that it plays an important role in the evolution of PPC. The metastases morphologically and genetically resembled the epithelial or the sarcomatoid components of the tumor. The transcriptomic and epigenetic profiles of the sarcomatoid components of PPCs with matched squamous-like or adenocarcinoma-like components differed from each other, and they shared more similarities to their matched epithelial components. NCAM1/CD56 was preferentially expressed in the sarcomatoid component of squamous-like PPCs, whereas CDH1/E-Cadherin expression was down-regulated in the sarcomatoid component of most PPCs., Conclusion: Lung adenocarcinoma-like PPCs are mainly driven by RTK-RAS signaling, whereas epithelial-mesenchymal transition programs as highlighted by increased NCAM1 and decreased CDH1 expression govern the epithelial-sarcomatoid transition between the clonally related tumor components. Several alterations in PPCs pinpoint therapeutic opportunities., Competing Interests: Disclosure The authors report no conflicts of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Published
2024
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47. RGD Density on Tadpole Nanostructures Regulates Cancer Stem Cell Proliferation and Stemness.

Author

Zhang D, Sun B, Wang J, Chen SR, Bobrin VA, Gu Y, Ng CK, Gu W, and Monteiro MJ

Subjects
Humans, Animals, Nanostructures chemistry, Cell Line, Tumor, Nanoparticles chemistry, Neoplastic Stem Cells pathology, Neoplastic Stem Cells metabolism, Oligopeptides chemistry, Oligopeptides pharmacology, Cell Proliferation drug effects
Abstract

Cancer stem cells (CSCs) make up a small population of cancer cells, primarily responsible for tumor initiation, metastasis, and drug resistance. They overexpress Arg-Gly-Asp (RGD) binding integrin receptors that play crucial roles in cell proliferation and stemness through interaction with the extracellular matrix. Here, we showed that monodisperse polymeric tadpole nanoparticles covalently coupled with different RGD densities regulated colon CSC proliferation and stemness in a RGD density-dependent manner. These tadpoles penetrated deeply and evenly into tumor spheroids and specifically entered cells with cancer stem markers CD24 and CD133. Low RGD density tadpoles triggered integrin α5 expression that further activated TGF-β3 and TGF-β2 signaling pathways, confirmed by the increase of pERK and Bcl-2 protein levels. This process is associated with the RGD cluster presentation controlled by the RGD density on the tadpole surface.

Published
2024
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48. Use of patient-reported experience and outcome measures within the colorectal cancer care continuum: a scoping review.

Author

Lau J, Ng JS, Lee D, Tan JK, Tan LL, Pang NQ, Tham SY, Ng CK, and Tan KK

Abstract

Objective: Patient-reported outcome measures (PROM) are frequently adopted to evaluate colorectal cancer (CRC) care, but the use of patient-reported experience measures (PREM) appears to be underdeveloped and not widely validated. This scoping review aims to understand the contexts for deployment of PREMs in CRC care, reliability of measures, gaps in current use of PREMs, and how PREMs are associated with PROMs when deployed together., Methods: Four scientific databases (PubMed, CINAHL, PsycINFO, Scopus) were systematically searched from January 2011 to December 2023. Observational or interventional studies involving quantitative or mixed methodology with samples consisting CRC patients undergoing screening, treatment, or cancer surveillance and utilizing at least one PREM as an exposure or outcome were included., Results: The initial search resulted in 10,400 records. Only 13 relevant studies (consisting of 17,105 participants) met the eligibility criteria. Utilization of PREMs was heterogenous across our sample and the CRC care continuum, and about half of the studies (53.8%) evaluated the relationship between PREMs and PROMs. PREM usage across the CRC care continuum largely focused on treatment/survivorship. Better care experience was positively associated with improved patient-reported outcomes., Conclusions: Future work in CRC PREM development should focus on (1) establishing validated measures that aim to either capture disease/treatment-specific granularity or capitalize on applicability across care settings, (2) localizing novel or existing PREMs to consider different cultural contexts in healthcare, and (3) benchmarking associations between PREMs, PROMs, and other outcomes of interest., Implications for Cancer Survivors: Individuals progressing through the CRC care continuum often undergo a multitude of procedures from detection and diagnosis to treatment and surveillance. The establishment of validated PREMs specific to CRC would help to benchmark and further improve the quality of care received-which should translate to better patient-reported outcomes-and serve as process indicators for institutions and providers to maintain rigorous health service delivery standard for CRC survivors., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2024
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50. Comparative evaluation of different modalities for measuring in vivo carnosine levels.

Author

Amraotkar AR, Hoetker D, Negahdar MJ, Ng CK, Lorkiewicz P, Owolabi US, Baba SP, Bhatnagar A, and O'Toole TE

Subjects
Male, Female, Humans, Muscle, Skeletal chemistry, Diet, Leg, Tandem Mass Spectrometry, Carnosine
Abstract

Carnosine is an endogenous di-peptide (β-alanine -L- histidine) involved in maintaining tissue homeostasis. It is most abundant in skeletal muscle where its concentration has been determined in biopsy samples using tandem mass spectrometry (MS-MS). Carnosine levels can also be assessed in intact leg muscles by proton magnetic resonance spectroscopy (1H-MRS) or in blood and urine samples using mass spectrometry. Nevertheless, it remains uncertain how carnosine levels from these distinct compartments are correlated with each other when measured in the same individual. Furthermore, it is unclear which measurement modality might be most suitable for large-scale clinical studies. Hence, in 31 healthy volunteers, we assessed carnosine levels in skeletal muscle, via 1H-MRS, and in erythrocytes and urine by MS-MS. While muscle carnosine levels were higher in males (C2 peak, p = 0.010; C4 peak, p = 0.018), there was no sex-associated difference in urinary (p = 0.433) or erythrocyte (p = 0.858) levels. In a linear regression model adjusted for age, sex, race, and diet, there was a positive association between erythrocyte and urinary carnosine. However, no association was observed between 1H-MRS and erythrocytes or urinary measures. In the relationship between muscle versus urinary and erythrocyte measures, females had a positive association, while males did not show any association. We also found that 1H-MRS measures were highly sensitive to location of measurement. Thus, it is uncertain whether 1H-MRS can accurately and reliably predict endogenous carnosine levels. In contrast, urinary and erythrocyte carnosine measures may be stable and in greater synchrony, and given financial and logistical concerns, may be a feasible alternative for large-scale clinical studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Amraotkar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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