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1. Targeting Patient-Derived Orthotopic Gastric Cancers with a Fluorescent Humanized Anti-CEA Antibody

Author

Cox, Kristin E, Turner, Michael A, Lwin, Thinzar M, Amirfakhri, Siamak, Kelly, Kaitlyn J, Hosseini, Mojgan, Ghosh, Pradipta, Obonyo, Marygorret, Hoffman, Robert M, Yazaki, Paul J, and Bouvet, Michael

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Orphan Drug, Rare Diseases, Digestive Diseases, 5.1 Pharmaceuticals, Stomach Neoplasms, Animals, Humans, Mice, Carcinoembryonic Antigen, Adenocarcinoma, Xenograft Model Antitumor Assays, Antibodies, Monoclonal, Humanized, Fluorescent Dyes, Tumor Cells, Cultured, Female, Indoles, Optical Imaging, Gastrectomy, Mice, Nude, Cell Line, Tumor, Gastric cancer, Patient-derived orthotopic xenograft, PDOX, Fluorescence, Fluorescent antibody, CEA, Tumor targeting, Tumor labeling, Gastric cancer, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundGastric cancer poses a major diagnostic and therapeutic challenge as surgical resection provides the only opportunity for a cure. Specific labeling of gastric cancer could distinguish resectable and nonresectable disease and facilitate an R0 resection, which could improve survival.MethodsTwo patient-derived gastric cancer lines, KG8 and KG10, were established from surgical specimens of two patients who underwent gastrectomy for gastric adenocarcinoma. Harvested tumor fragments were implanted into the greater curvature of the stomach to establish patient-derived orthotopic xenograft (PDOX) models. M5A (humanized anti-CEA antibody) or IgG control antibodies were conjugated with the near-infrared dye IRDye800CW. Mice received 50 µg of M5A-IR800 or 50 µg of IgG-IR800 intravenously and were imaged after 72 hr. Fluorescence imaging was performed by using the LI-COR Pearl Imaging System. A tumor-to-background ratio (TBR) was calculated by dividing the mean fluorescence intensity of the tumor versus adjacent stomach tissue.ResultsM5A-IR800 administration resulted in bright labeling of both KG8 and K10 tumors. In the KG8 PDOX models, the TBR for M5A-IR800 was 5.85 (SE ± 1.64) compared with IgG-IR800 at 0.70 (SE ± 0.17). The K10 PDOX models had a TBR of 3.71 (SE ± 0.73) for M5A-IR800 compared with 0.66 (SE ± 0.12) for IgG-IR800.ConclusionsHumanized anti-CEA (M5A) antibodies conjugated to fluorescent dyes provide bright and specific labeling of gastric cancer PDOX models. This tumor-specific fluorescent antibody is a promising potential clinical tool to detect the extent of disease for the determination of resectability as well as to visualize tumor margins during gastric cancer resection.

Published
2024

2. Quantifying the uncertainty in the time-redshift relationship

Author

Turner, Michael S.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

The age of the Universe at a given redshift is a fundamental relationship in cosmology. For many years, the uncertainties in it were dauntingly large, close to a factor of 2. In this age of precision cosmology, they are now at the percent level and dominated by the uncertainty in the Hubble constant. The uncertainties due to the parameters that describe the current cosmological model, $\Lambda$CDM, are much less important. In decreasing order they are: uncertainty due to the matter density $\Omega_M$ around 0.9\% for $z> 3$; uncertainty due to the dark energy equation-of-state parameter $w$, less than 0.3\% for $z>3$; and uncertainty due to the curvature parameter $\Omega_k$, at most 0.07\%., Comment: New version corrects typos and adds a reference

Published
2024

3. TRIF-IFN-I pathway in Helicobacter-induced gastric cancer in an accelerated murine disease model and patient biopsies

Author

Bali, Prerna, Lozano-Pope, Ivonne, Hernandez, Jonathan, Estrada, Monica V, Corr, Maripat, Turner, Michael A, Bouvet, Michael, Benner, Christopher, and Obonyo, Marygorret

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases - (Peptic Ulcer), Emerging Infectious Diseases, Rare Diseases, Infectious Diseases, Cancer, Digestive Diseases, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Biological sciences, Clinical microbiology, Microbiology
Abstract

Helicobacter pylori (H. pylori) infection is a known cause of many digestive diseases, including gastritis, peptic ulcers, and gastric cancer. However, the underlying mechanisms by which H. pylori infection triggers these disorders are still not clearly understood. Gastric cancer is a slow progressing disease, which makes it difficult to study. We have developed an accelerated disease progression mouse model, which leverages mice deficient in the myeloid differentiation primary response 88 gene (Myd88-/-) infected with Helicobacter felis (H. felis). Using this model and gastric biopsy samples from patients, we report that activation of the Toll/interleukin-1 receptor (TIR)-domain-containing adaptor inducing interferon-β (TRIF)-type I interferon (IFN-I) signaling pathway promotes Helicobacter-induced disease progression toward severe gastric pathology and gastric cancer development. Further, results implicated downstream targets of this pathway in disease pathogenesis. These findings may facilitate stratification of Helicobacter-infected patients and thus enable treatment prioritization of patients.

Published
2024

4. Skew Axial Algebras of Monster Type II

Author

Turner, Michael

Subjects
Mathematics - Rings and Algebras, Mathematics - Group Theory
Abstract

In our first paper, we looked at $2$-generated primitive axial algebras of Monster type with skew axet $X'(1+2)$. We continue our work by focusing on larger skew axets and classifying all such algebras with skew axets. This brings us one step closer to a complete classification of all $2$-generated primitive axial algebras of Monster type., Comment: 16 pages; typos fixed and even argument simplified

Published
2023

5. Humanized Anti-Carcinoembryonic Antigen Antibodies Brightly Target and Label Gastric Cancer in Orthotopic Mouse Models

Author

Cox, Kristin E, Turner, Michael A, Amirfakhri, Siamak, Lwin, Thinzar M, Hosseini, Mojgan, Ghosh, Pradipta, Obonyo, Marygorret, Murakami, Takashi, Hoffman, Robert M, Yazaki, Paul J, and Bouvet, Michael

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Biotechnology, Cancer, Digestive Diseases, Rare Diseases, 5.1 Pharmaceuticals, Humans, Animals, Mice, Stomach Neoplasms, Mice, Nude, Carcinoembryonic Antigen, Antibodies, Monoclonal, Disease Models, Animal, Immunoglobulin G, Fluorescent Dyes, Cell Line, Tumor, CEA, Gastric cancer, Orthotopic mouse model, Fluorescence, Fluorescent antibody, Tumor labeling, Clinical Sciences, Surgery, Clinical sciences
Abstract

IntroductionGastric cancer poses a major therapeutic challenge. Improved visualization of tumor margins at the time of gastrectomy with fluorescent tumor-specific antibodies could improve outcomes. The present report demonstrates the potential of targeting gastric cancer with a humanized anti-carcinoembryonic antigen (CEA) antibody in orthotopic mouse models.MethodsMKN45 cells were injected subcutaneously into nude mice to establish xenograft models. Tumor fragments collected from subcutaneous models were then implanted into the greater curvature of the stomach to establish orthotopic models. For tumor labeling, a humanized anti-CEA antibody (M5A) and IgG as a control, were conjugated with the near-infrared dye IRDye800CW. Time (24-72 h) and dose (50-100 μg) response curves were performed in subcutaneous models. Orthotopic models received 50 μg of M5A-IR800 or 50 μg IgG-IR800 as a control and were imaged after 72 h. Fluorescence imaging was performed on the mice using the LI-COR Pearl Imaging System.ResultsIn subcutaneous models, tumor to background ratios (TBRs) reached 8.85 at 72 h. Median TBRs of orthotopic model primary tumors were 6.25 (interquartile range [IQR] 6.03-7.12) for M5A-IR800 compared to 0.42 (IQR 0.38-0.54) for control. Abdominal wall metastasis median TBRs were 13.52 (IQR 12.79-13.76) for M5A-IR800 and 3.19 (IQR 2.65-3.73) for the control. Immunohistochemistry confirmed CEA expression within tumors.ConclusionsHumanized anti-CEA antibodies conjugated to near-infrared dyes provide specific labeling of gastric cancers in mouse models. Orthotopic models demonstrated bright and specific labeling with TBRs greater than ten times that of control. This tumor-specific fluorescent antibody is a promising potential clinical tool for improving visualization of gastric cancer margins at time of surgical resection.

Published
2024

7. Skew Axial Algebras of Monster Type

Author

Turner, Michael

Subjects
Mathematics - Rings and Algebras, Mathematics - Group Theory
Abstract

Skew axets were first defined by McInroy and Shpectorov where they used the term of axets to classify shapes of an algebra. When they first submitted their paper, it was not known if skew axial algebras exist and now we will present such examples with axet $X'(1+2)$. Looking at $2$-generated primitive axial algebras of Monster type, we will be able to state and prove the classification of such algebras with axet $X'(1+2)$. We will conclude by looking at larger skew axets and give a suggestion on how one could extend the classification., Comment: 29 pages; typos and errors fixed

Published
2023

8. Specific Targeting and Labeling of Colonic Polyps in CPC-APC Mice with Mucin 5AC Fluorescent Antibodies: A Model for Detection of Early Colon Cancer

Author

Turner, Michael A, Cox, Kristin E, Liu, Shanglei, Neel, Nicholas, Amirfakhri, Siamak, Nishino, Hiroto, Hosseini, Mojgan, Alcantara, Joshua A, El-Hafeez, Amer Ali Abd, Lwin, Thinzar M, Mallya, Kavita, Pisegna, Joseph R, Singh, Satish K, Ghosh, Pradipta, Hoffman, Robert M, Batra, Surinder K, and Bouvet, Michael

Subjects
Microbiology, Biological Sciences, Prevention, Cancer, Colo-Rectal Cancer, Digestive Diseases, colorectal cancer, polyps, fluorescence, fluorescence labeling, mucin, detection, genetically engineered mouse models, Medical Microbiology
Abstract

Poor visualization of polyps can limit colorectal cancer screening. Fluorescent antibodies to mucin5AC (MUC5AC), a glycoprotein upregulated in adenomas and colorectal cancer, could improve screening colonoscopy polyp detection rate. Adenomatous polyposis coli flox mice with a Cdx2-Cre transgene (CPC-APC) develop colonic polyps that contain both dysplastic and malignant tissue. Mice received MUC5AC-IR800 or IRdye800 as a control IV and were sacrificed after 48 h for near-infrared imaging of their colons. A polyp-to-background ratio (PBR) was calculated for each polyp by dividing the mean fluorescence intensity of the polyp by the mean fluorescence intensity of the background tissue. The mean 25 μg PBR was 1.70 (±0.56); the mean 50 μg PBR was 2.64 (±0.97); the mean 100 μg PBR was 3.32 (±1.33); and the mean 150 μg PBR was 3.38 (±0.87). The mean PBR of the dye-only control was 2.22 (±1.02), significantly less than the 150 μg arm (p-value 0.008). The present study demonstrates the ability of fluorescent anti-MUC5AC antibodies to specifically target and label colonic polyps containing high-grade dysplasia and intramucosal adenocarcinoma in CPC-APC mice. This technology can potentially improve the detection rate and decrease the miss rate of advanced colonic neoplasia and early cancer at colonoscopy.

Published
2023

9. Highly Selective Targeting of Pancreatic Cancer in the Liver with a Near-Infrared Anti-MUC5AC Probe in a PDOX Mouse Model: A Proof-of-Concept Study

Author

Turner, Michael A, Cox, Kristin E, Neel, Nicholas, Amirfakhri, Siamak, Nishino, Hiroto, Clary, Bryan M, Hosseini, Mojgan, Natarajan, Gopalakrishnan, Mallya, Kavita, Mohs, Aaron M, Hoffman, Robert M, Batra, Surinder K, and Bouvet, Michael

Subjects
Rare Diseases, Cancer, Liver Disease, Orphan Drug, Pancreatic Cancer, Digestive Diseases, Development of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, 5.1 Pharmaceuticals, Aetiology, Good Health and Well Being, pancreatic cancer, liver metastasis, selective targeting, fluorescent antibody, imaging, mucin
Abstract

Accurately identifying metastatic disease is critical to directing the appropriate treatment in pancreatic cancer. Mucin 5AC is overexpressed in pancreatic cancer but absent in normal pancreas tissue. The present proof-of-concept study demonstrates the efficacy of an anti-mucin 5AC antibody conjugated to an IR800 dye (MUC5AC-IR800) to preferentially label a liver metastasis of pancreatic cancer (Panc Met) in a unique patient-derived orthotopic xenograft (PDOX) model. In orthotopic models, the mean tumor to background ratio was 1.787 (SD ± 0.336), and immunohistochemistry confirmed the expression of MUC5AC within tumor cells. MUC5AC-IR800 provides distinct visualization of pancreatic cancer liver metastasis in a PDOX mouse model, demonstrating its potential utility in staging laparoscopy and fluorescence-guided surgery.

Published
2023

10. Proof of Principle of Combining Fluorescence-Guided Surgery with Photoimmunotherapy to Improve the Outcome of Pancreatic Cancer Therapy in an Orthotopic Mouse Model

Author

Nishino, Hiroto, Turner, Michael A, Amirfakhri, Siamak, Lwin, Thinzar M, Hosseini, Mojgan, Singer, Bernhard B, Hoffman, Robert M, and Bouvet, Michael

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Biotechnology, Rare Diseases, Pancreatic Cancer, Digestive Diseases, Humans, Mice, Animals, Mice, Nude, Pancreatic Neoplasms, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Pancreatic cancer is a recalcitrant disease in which R0 resection is often not achieved owing to difficulty in visualization of the tumor margins and proximity of adjacent vessels. To improve outcomes, we have developed fluorescence-guided surgery (FGS) and photoimmunotherapy (PIT) using a fluorescent tumor-specific antibody. Nude mice received surgical orthotopic implantation (SOI) of the human pancreatic cancer cell line BxPC-3 expressing green fluorescent protein. An anti-carcinoembryonic antigen-related cell adhesion molecule (CEACAM) monoclonal antibody (6G5j) was conjugated to the 700-nm fluorescent dye IR700DyeDX (6G5j-IR700DX). Three weeks after SOI, 16 mice received 50 μg 6G5j-IR700DX via the tail vein 24 h before surgery and were randomized to two groups: FGS-only (n = 8) and FGS + PIT (n = 8). All tumors were imaged with the Pearl Trilogy imaging system and resected under the guidance of the FLARE imaging system. The FGS + PIT group received PIT of the post-surgical bed at an intensity of 150 mW/cm2 for 30 min. Mice were sacrificed 4 weeks after initial surgery, and tumors were imaged with a Dino-Lite digital microscope, excised, and weighed. The 6G5j-IR700DX dye illuminated the orthotopic pancreatic tumors for FGS and PIT. The metastatic recurrence rate was 100.0% for FGS-only and 25.0% for FGS + PIT (p = 0.007). The average total recurrent tumor weight was 2370.3 ± 1907.8 mg for FGS-only and 705.5 ± 1200.0 mg for FGS + PIT (p = 0.039). FGS and adjuvant PIT can be combined by using a single antibody-fluorophore conjugate to significantly reduce the frequency of pancreatic cancer recurrence.

Published
2023

11. Anti-mucin 4 fluorescent antibody brightly targets colon cancer in patient-derived orthotopic xenograft mouse models: A proof-of-concept study for future clinical applications

Author

Turner, Michael A, Hollandsworth, Hannah M, Amirfakhri, Siamak, Lwin, Thinzar M, Nishino, Hiroto, Neel, Nicholas C, Natarajan, Gopalakrishnan, Kaur, Sukhwinder, Mallya, Kavita, Hoffman, Robert M, Batra, Surinder K, and Bouvet, Michael

Subjects
Digestive Diseases, Liver Disease, Rare Diseases, Colo-Rectal Cancer, Biotechnology, Cancer, Animals, Colonic Neoplasms, Disease Models, Animal, Heterografts, Humans, Liver Neoplasms, Mice, Mice, Nude, Clinical Sciences, Surgery
Abstract

BackgroundThere is a high rate of positive surgical margins with resection of liver metastases in colorectal cancer (CRC). The present study reports using a fluorescent anti-mucin 4 (MUC4) antibodies to label primary CRC and liver metastases to better visualize tumor margins in mouse models.MethodsWestern blotting for MUC4 protein expression of normal colon and CRC tumor lysates was performed. Orthotopic primary and liver metastatic CRC mouse models received anti-MUC4 antibody conjugated to IR800 (MUC4-IR800). Mice were sacrificed and imaged after 48 hours.ResultsWestern blotting demonstrated increased MUC4 expression in a human CRC cell line and patient-derived primary and liver-metastatic CRCs. The LS174T orthotopic primary CRC model tumor to background ratio (TBR) was 2.04 (±0.35). The patient-derived orthotopic xenograft (PDOX) primary CRC model TBR was 2.17 (±0.35). The PDOX liver metastasis model TBR was 1.56 (±0.53).ConclusionMUC4-IR800 provided bright labeling of primary and liver tumors in CRC orthotopic mouse models, demonstrating their future clinical potential for margin visualization in fluorescence guided surgery.

Published
2022

12. The Road to Precision Cosmology

Author

Turner, Michael S.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics, General Relativity and Quantum Cosmology, High Energy Physics - Phenomenology
Abstract

The past 50 years has seen cosmology go from a field known for the errors being in the exponents to precision science. The transformation, powered by ideas, technology, a paradigm shift and culture change, has revolutionized our understanding of the Universe, with the $\Lambda$CDM paradigm as its crowning achievement. I chronicle the journey of precision cosmology and finish with my thoughts about what lies ahead., Comment: Submitted to Annual Review of Nuclear and Particle Science. To appear in volume 32; doi: 10.1146/annurev-nucl-111119-041046. Comments and suggestions welcome

Published
2022
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13. Genotyping, sequencing and analysis of 140,000 adults from Mexico City

Author

Ziyatdinov, Andrey, Torres, Jason, Alegre-Díaz, Jesús, Backman, Joshua, Mbatchou, Joelle, Turner, Michael, Gaynor, Sheila M., Joseph, Tyler, Zou, Yuxin, Liu, Daren, Wade, Rachel, Staples, Jeffrey, Panea, Razvan, Popov, Alex, Bai, Xiaodong, Balasubramanian, Suganthi, Habegger, Lukas, Lanche, Rouel, Lopez, Alex, Maxwell, Evan, Jones, Marcus, García-Ortiz, Humberto, Ramirez-Reyes, Raul, Santacruz-Benítez, Rogelio, Nag, Abhishek, Smith, Katherine R., Damask, Amy, Lin, Nan, Paulding, Charles, Reppell, Mark, Zöllner, Sebastian, Jorgenson, Eric, Salerno, William, Petrovski, Slavé, Overton, John, Reid, Jeffrey, Thornton, Timothy A., Abecasis, Gonçalo, Berumen, Jaime, Orozco-Orozco, Lorena, Collins, Rory, Baras, Aris, Hill, Michael R., Emberson, Jonathan R., Marchini, Jonathan, Kuri-Morales, Pablo, and Tapia-Conyer, Roberto

Published
2023
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14. Understanding BBN: the physics and its history

Author

Turner, Michael S., KICP/UChicago, and Foundation, The Kavli

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics, High Energy Physics - Phenomenology
Abstract

Big-bang nucleosynthesis (BBN), today a pillar of modern cosmology, began with the trailblazing 1948 paper of Alpher, Bethe and Gamow. In it, they proposed non-equilibrium nuclear processes in the early Universe ($t \sim 1000\,$sec) and an early radiation-dominated phase to explain the abundances of all the chemical elements. Their model was fundamentally flawed, but initiated a complex and interesting path to the modern theory of BBN, which explains only the abundances of the lightest chemical elements (mostly $^4$He) and the discovery of the cosmic microwave background (CMB). The purpose of this paper is to clarify the basic physics of BBN, adding some new insights, and to describe how the modern theory developed. I finish with a discussion of two misunderstandings about BBN that still persist and the tale of the pre-discovery predictions of the temperature of the CMB and the missed opportunity it turned out to be., Comment: Significantly revised with new title. Content is largely the same; presentation changes reflect valuable comments from colleagues

Published
2021

15. $\Lambda$CDM: Much more than we expected, but now less than what we want

Author

Turner, Michael S.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics, High Energy Physics - Phenomenology
Abstract

The $\rm\Lambda$CDM cosmological model is remarkable: with just 6 parameters it describes the evolution of the Universe from a very early time when all structures were quantum fluctuations on subatomic scales to the present, and it is consistent with a wealth of high-precision data, both laboratory measurements and astronomical observations. However, the foundation of $\rm\Lambda$CDM involves physics beyond the standard model of particle physics: particle dark matter, dark energy and cosmic inflation. Until this `new physics' is clarified, $\rm\Lambda$CDM is at best incomplete and at worst a phenomenological construct that accommodates the data. I discuss the path forward, which involves both discovery and disruption, some grand challenges and finally the limits of scientific cosmology., Comment: Proceedings of the Lemaitre Workshop on Black Holes, Gravitational Waves and Space Time Singularities, published in Foundations of Physics (2018)

Published
2021

16. The third cosmological paradigm

Author

Turner, Michael S.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics, High Energy Physics - Phenomenology
Abstract

I begin by briefly discussing the first two cosmological paradigms, the hot big-bang model and $\Lambda$CDM. In discussing the third paradigm, I focus on the issues it must address, what its aspirations should be, and how it might be initiated. I end with a brief history of my collaborations with Frank Wilczek., Comment: Contribution to Quantum Connections 2021, a small post-pandemic workshop that we organize to celebrate Frank Wilczek's many interests in physics and his 70th birthday. Held in H\"ogberga G{\aa}rd, Liding\"o, Sweden, 21 to 25 June 2021

Published
2021

18. Malodour classification with low-cost flexible electronics

Author

Ozer, Emre, Kufel, Jedrzej, Biggs, John, Rana, Anjit, Rodriguez, Francisco J., Lee-Clark, Thomas, Sou, Antony, Ramsdale, Catherine, White, Scott, Garlapati, Suresh Kumar, Valliappan, Palaniappan, Rahmanudin, Aiman, Komanduri, Venuskrishnan, Saez, Glenn Sunley, Gollu, Sankara, Brown, Gavin, Dudek, Piotr, Persaud, Krishna C., Turner, Michael L., Murray, Stephanie, Bates, Susan, Treloar, Robert, Newby, Brian, and Ford, Jane

Published
2023
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19. Genomically Silent Refractory Gastric Cancer in a Young Patient Exhibits Overexpression of CXCL5

Author

Hernandez, Jonathan, Turner, Michael A, Bali, Prerna, Hosseini, Mojgan, Bouvet, Michael, Kelly, Kaitlyn, and Obonyo, Marygorret

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Emerging Infectious Diseases, Rare Diseases, Infectious Diseases, Genetics, Digestive Diseases, Digestive Diseases - (Peptic Ulcer), 4.1 Discovery and preclinical testing of markers and technologies, Aetiology, Detection, screening and diagnosis, 2.1 Biological and endogenous factors, Adult, Chemokine CXCL5, Genetic Testing, Germ-Line Mutation, Helicobacter Infections, Helicobacter pylori, Humans, Stomach Neoplasms, young patient, advanced gastric cancer, CDH1, CXCL5, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Gastric cancer is the third leading cause of cancer-related deaths, with more than one million new cases and approximately 841,000 deaths annually worldwide. We report a case of a young patient (25 years old) with an aggressive form of gastric cancer. The patient had previously been treated for Helicobacter pylori (H. pylori), which is a main risk factor for developing gastric cancer. Genetic testing showed an E-cadherin (CDH1) germline mutation of unknown significance. After eight cycles of chemotherapy, a positron emission tomography (PET) scan showed disease progression with an enlarging hypermetabolic right adnexal mass suspicious for metastatic disease. Tumor pathology demonstrated invasive and poorly differentiated gastric carcinoma. The analysis of the tumor biopsy indicated the very high expression of a chemokine, C-X-C motif chemokine 5 (CXCL5). The combination of H. pylori infection with an existence of a rare CDH1 mutation could have contributed to this aggressive gastric cancer.

Published
2022

20. Fluorescent Anti-MUC5AC Brightly Targets Pancreatic Cancer in a Patient-derived Orthotopic Xenograft

Author

Turner, Michael A, Hollandsworth, Hannah M, Nishino, Hiroto, Amirfakhri, Siamak, Lwin, Thinzar M, Lowy, Andrew M, Kaur, Sukhwinder, Natarajan, Gopalakrishnan, Mallya, Kavita, Hoffman, Robert M, Batra, Surinder K, and Bouvet, Michael

Subjects
Rare Diseases, Orphan Drug, Biotechnology, Digestive Diseases, Pancreatic Cancer, Cancer, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Animals, Fluorescent Dyes, Heterografts, Humans, Mice, Mice, Nude, Pancreatic Neoplasms, Xenograft Model Antitumor Assays, Pancreatic cancer, mucin, MUC5AC, antibody, tumor-specific imaging, fluorescence guided surgery, PDOX, Clinical Sciences, Oncology & Carcinogenesis
Abstract

BackgroundOverexpression of mucin-5AC (MUC5AC) makes it a targetable biomarker in pancreatic cancer. The present study evaluated tumor targeting with a MUC5AC antibody conjugated to a near-infrared dye in a patient-derived orthotopic xenograft (PDOX) mouse model.Materials and methodsMUC5AC monoclonal antibody was conjugated to the near-infrared dye IRDye800CW to synthesize MUC5AC-IR800. PDOX models were established by implanting a high-MUC5AC-expressing patient-derived pancreatic tumor on the pancreas of nude mice. After 4 weeks of PDOX tumor growth, mice were imaged after receiving MUC5AC-IR800 (75 μg) intravenously.ResultsIn the PDOX models, MUC5AC-IR800 selectively and brightly targeted the pancreatic tumor (tumor to background ratio: 2.46±0.465).ConclusionMUC5AC-IR800 provides distinct visualization of pancreatic tumors. MUC5AC-IR800 may be used clinically in the future to improve pancreatic cancer resection. This novel fluorescent probe is also promising for targeting of pre-malignant pancreatic lesions with subsequent resection under fluorescence guidance.

Published
2022

21. Fluorescent Anti-CEA Nanobody for Rapid Tumor-Targeting and Imaging in Mouse Models of Pancreatic Cancer

Author

Lwin, Thinzar M, Turner, Michael A, Nishino, Hiroto, Amirfakhri, Siamak, Hernot, Sophie, Hoffman, Robert M, and Bouvet, Michael

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Pancreatic Cancer, Biotechnology, Digestive Diseases, Rare Diseases, Brain Cancer, Brain Disorders, Cancer, Animals, Diagnostic Imaging, Disease Models, Animal, Humans, Mice, Pancreatic Neoplasms, Single-Domain Antibodies, nanobodies, pancreatic cancer, patient derived orthotopic xenograft, CEA, fluorescenceguided-surgery, fluorescence, near-infrared, IRDye800CW, tumor labeling, fluorescence-guided-surgery, Biochemistry and Cell Biology, Biochemistry and cell biology, Bioinformatics and computational biology, Medical biotechnology
Abstract

Tumor-specific targeting with fluorescent probes can enhance contrast for identification of cancer during surgical resection and visualize otherwise invisible tumor margins. Nanobodies are the smallest naturally-occurring antigen-binding molecules with rapid pharmacokinetics. The present work demonstrates the efficacy of a fluorescent anti-CEA nanobody conjugated to an IR800 dye to target and label patient derived pancreatic cancer xenografts. After intravenous administration, the probe rapidly localized to the pancreatic cancer tumors within an hour and had a tumor-to-background ratio of 2.0 by 3 h. The fluorescence signal was durable over a prolonged period of time. With the rapid kinetics afforded by fluorescent nanobodies, both targeting and imaging can be performed on the same day as surgery.

Published
2022

22. Fluorescence Molecular Targeting of Colon Cancer to Visualize the Invisible

Author

Lwin, Thinzar M, Turner, Michael A, Amirfakhri, Siamak, Nishino, Hiroto, Hoffman, Robert M, and Bouvet, Michael

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Bioengineering, Cancer, Clinical Research, Colo-Rectal Cancer, Clinical Trials and Supportive Activities, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Animals, Biomarkers, Tumor, Colonic Neoplasms, Fluorescence, Fluorescent Dyes, Humans, Molecular Targeted Therapy, tumor-specific antibodies, fluorescent dyes, tumor-specific labeling, fluorescence-guided surgery, Biological sciences, Biomedical and clinical sciences
Abstract

Colorectal cancer (CRC) is a common cause of cancer and cancer-related death. Surgery is the only curative modality. Fluorescence-enhanced visualization of CRC with targeted fluorescent probes that can delineate boundaries and target tumor-specific biomarkers can increase rates of curative resection. Approaches to enhancing visualization of the tumor-to-normal tissue interface are active areas of investigation. Nonspecific dyes are the most-used approach, but tumor-specific targeting agents are progressing in clinical trials. The present narrative review describes the principles of fluorescence targeting of CRC for diagnosis and fluorescence-guided surgery with molecular biomarkers for preclinical or clinical evaluation.

Published
2022

23. Rapidly-converging multigrid reconstruction of cone-beam tomographic data

Author

Myers, Glenn R., Kingston, Andrew M., Latham, Shane J., Recur, Benoit, Li, Thomas, Turner, Michael L., Beeching, Levi, and Sheppard, Adrian P.

Subjects
Physics - Medical Physics, Statistics - Applications
Abstract

In the context of large-angle cone-beam tomography (CBCT), we present a practical iterative reconstruction (IR) scheme designed for rapid convergence as required for large datasets. The robustness of the reconstruction is provided by the "space-filling" source trajectory along which the experimental data is collected. The speed of convergence is achieved by leveraging the highly isotropic nature of this trajectory to design an approximate deconvolution filter that serves as a pre-conditioner in a multi-grid scheme. We demonstrate this IR scheme for CBCT and compare convergence to that of more traditional techniques., Comment: 7 pages, 4 figures

Published
2021

24. Rapid tumor‐labeling kinetics with a site‐specific near‐infrared anti‐CEA nanobody in a patient‐derived orthotopic xenograft mouse model of colon cancer

Author

Lwin, Thinzar M, Turner, Michael A, Amirfakhri, Siamak, Nishino, Hiroto, Debie, Pieterjan, Cosman, Bard C, Hoffman, Robert M, Hernot, Sophie, and Bouvet, Michael

Subjects
Biotechnology, Digestive Diseases, Cancer, Colo-Rectal Cancer, Animals, Carcinoembryonic Antigen, Colonic Neoplasms, Disease Models, Animal, Fluorescent Dyes, Heterografts, Humans, Mice, Nude, Neoplasms, Experimental, Optical Imaging, Single-Domain Antibodies, anti-CEA nanobody, fluorescence-guided surgery, fluorescent anti-CEA nanobody, patient-derived orthotopic xenograft models, tumor-specific fluorescence, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Background/objectivesNanobodies are the smallest biologic antigen-binding fragments derived from camelid-derived antibodies. Nanobodies effect a peak tumor signal within minutes of injection and present a novel opportunity for fluorescence-guided surgery (FGS). The present study demonstrates the efficacy of an anti-CEA nanobody conjugated to near-infrared fluorophore LICOR-IRDye800CW for rapid intraoperative tumor labeling of colon cancer.MethodsLS174T human colon cancer cells or fragments of patient-derived colon cancer were implanted subcutaneously or orthotopically in nude mice. Anti-CEA nanobodies were conjugated with IRDye800CW and 1-3 nmol were injected intravenously. Mice were serially imaged over time. Peak fluorescence signal and tumor-to-background ratio (TBR) were recorded.ResultsColon cancer tumors were detectable using fluorescent anti-CEA nanobody within 5 min of injection at all three doses. Maximal fluorescence intensity was observed within 15 min-3 h for all three doses with TBR values ranging from 1.3 to 2.3. In the patient-derived model of colon cancer, fluorescence was detectable with a TBR of 4.6 at 3 h.ConclusionsFluorescent anti-CEA nanobodies rapidly and specifically labeled colon cancer in cell-line-based and patient-derived orthotopic xenograft (PDOX) models. The kinetics of nanobodies allow for same day administration and imaging. Anti-CEA-nb-800 is a promising and practical molecule for FGS of colon cancer.

Published
2021

26. Interim report on snakebite incidence and case fatality rates in sub-Saharan Africa/Rapport interimaire sur l'incidence des morsures de serpent et les taux de letalite associes en Afrique subsaharienne

Author

Kanankege, Kaushi, Turner, Michael, Moos, Bethany, de Castaneda, Rafael Ruiz, Nidjergou, Yetema Noemie Nikiema, Korkor, Andrew Seidu, Achu, Dorothy, Abela-Ridder, Bernadette, and Williams, David

Subjects
Public health -- Health aspects -- Reports, Bites and stings -- Reports -- Health aspects, Government, Health, World Health Assembly -- Reports
Abstract

Background The aim of the WHO strategy for the prevention and control of snakebite envenoming is to reduce snakebite-related mortality and disability by 50% before the end of the decade. [...]

Published
2023

27. Industry-Relevant Implicit Large-Eddy Simulation of a High-Performance Road Car via Spectral/hp Element Methods

Author

Mengaldo, Gianmarco, Moxey, David, Turner, Michael, Moura, Rodrigo C., Jassim, Ayad, Taylor, Mark, Peiro, Joaquim, and Sherwin, Spencer J.

Subjects
Computer Science - Computational Engineering, Finance, and Science
Abstract

We present a successful deployment of high-fidelity Large-Eddy Simulation (LES) technologies based on spectral/hp element methods to industrial flow problems, which are characterized by high Reynolds numbers and complex geometries. In particular, we describe the numerical methods, software development and steps that were required to perform the implicit LES of a real automotive car, namely the Elemental Rp1 model. To the best of the authors' knowledge, this simulation represents the first fifth-order accurate transient LES of an entire real car geometry. Moreover, this constitutes a key milestone towards considerably expanding the computational design envelope currently allowed in industry, where steady-state modelling remains the standard. To this end, a number of novel developments had to be made in order to overcome obstacles in mesh generation and solver technology to achieve this simulation, which we detail in this paper. The main objective is to present to the industrial and applied mathematics community, a viable pathway to translate academic developments into industrial tools, that can substantially advance the analysis and design capabilities of high-end engineering stakeholders. The novel developments and results were achieved using the academic-driven open-source framework Nektar++.

Published
2020

28. A Novel Color-Coded Liver Metastasis Mouse Model to Distinguish Tumor and Adjacent Liver Segment

Author

Nishino, Hiroto, Hollandsworth, Hannah M, Amirfakhri, Siamak, Tashiro, Yoshihiko, Yamamoto, Jun, Turner, Michael A, Lwin, Thinzar M, Singer, Bernhard B, Hoffman, Robert M, and Bouvet, Michael

Subjects
Liver Disease, Biotechnology, Colo-Rectal Cancer, Digestive Diseases, Cancer, Animals, Antibodies, Monoclonal, Carcinoembryonic Antigen, Colonic Neoplasms, Color, Fluorescent Dyes, GPI-Linked Proteins, Hepatectomy, Humans, Indocyanine Green, Injections, Intravenous, Liver, Liver Neoplasms, Mice, Molecular Imaging, Optical Imaging, Xenograft Model Antitumor Assays, Liver metastases, Colon cancer, Nude mouse model, Indocyanine green, Fluorescent tumor-specific antibody, CEACAM, Color-coded fluorescence imaging, Clinical Sciences, Surgery
Abstract

BackgroundIt is difficult to distinguish between a tumor and its liver segment with traditional use of indocyanine green (ICG) alone. In the present study, a method was used to limit ICG to the liver segment adjacent to a tumor. A spectrally-distinct fluorescently-labeled tumor-specific antibody against human carcinoembryonic antigen-related cell-adhesion molecules was used to label the metastatic tumor in a patient-derived orthotopic xenograft mouse model to enable color-coded visualization and distinction of a colon-cancer liver metastases and its adjacent liver segment.Materials and methodsNude mice received surgical orthotopic implantation in the liver of colon-cancer liver metastases derived from two patients. An anti- carcinoembryonic antigen-related cell-adhesion molecules monoclonal antibody (mAb 6G5j) was conjugated to a near-infrared dye IR700DX (6G5j-IR700DX). After three weeks, mice received 6G5j-IR700DX via tail-vein injection 48 hours before surgery. ICG was intravenously injected after ligation of the left or left lateral Glissonean pedicle resulting in labeling of the segment with preserved blood-flow in the liver. Imaging was performed with the Pearl Trilogy and FLARE Imaging Systems.ResultsThe metastatic liver tumor had a clear fluorescence signal due to selective tumor targeting by 6G5j-IR700DX, which was imaged on the 700 nm channel. The adjacent liver segment, with preserved blood-flow in the liver, had a clear fluorescence ICG 800 nm signal, while the left or left lateral segment had no fluorescence signal. Overlay of the images showed clear color-coded differentiation between the tumor fluorescing at 700 nm and the adjacent liver segment fluorescing at 800 nm.ConclusionsColor-coding of a liver tumor and uninvolved liver segment has the potential for improved liver resection.

Published
2021

29. A review of tumor-specific fluorescence-guided surgery for colorectal cancer

Author

Hollandsworth, Hannah M, Turner, Michael A, Hoffman, Robert M, and Bouvet, Michael

Subjects
Digestive Diseases, Cancer, Colo-Rectal Cancer, Biomedical Imaging, Colorectal Neoplasms, Fluorescence, Fluorescent Dyes, Humans, Optical Imaging, Surgery, Computer-Assisted, Fluorescence-guided surgery, Colorectal cancer, Tumor-specific antibodies, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

The present study reviews the use of tumor-specific antibodies conjugated to fluorescent dyes in preclinical and clinical studies to enhance visualization of primary tumors and metastases for fluorescence-guided surgery (FGS) in colorectal cancer (CRC). A search strategy was developed using the peer-reviewed National Center for Biotechnology Information (NCBI) database on PubMed. Studies using tumor-specific fluorescence imaging and FGS techniques on murine models of colorectal cell lines or patient-derived orthotopic xenograft (PDOX) colorectal cancer are reviewed. A total of 24 articles were identified that met the inclusion criteria, 21 preclinical and 3 clinical trials. The most widely used target antigen in preclinical and clinical trials was carcinoembryonic antigen (CEA). Mouse studies and clinical studies have demonstrated that the use of FGS in CRC can aid in decreased residual tumor and decreased rates of recurrence. As the mainstay of colorectal cancer treatment is surgery, the addition of intraoperative fluorescence imaging can help locate tumor margins, visualize occult micro-metastases, drive surgical decision making and improve patient outcomes.

Published
2021

30. A Patient-Derived Orthotopic Xenograft Model of Gastroesophageal-Junction Adenocarcinoma Translated to the Clinic by Tumor-Targeting Fluorescent Antibodies to Carcinoembryonic-Antigen-Related Cell-Adhesion Molecules

Author

Turner, Michael A, Amirfakhri, Siamak, Nishino, Hiroto, Lwin, Thinzar M, Savides, Thomas J, Reid, Tony R, Singer, Bernhard B, Hoffman, Robert M, and Bouvet, Michael

Subjects
Cancer, Rare Diseases, Digestive Diseases, Adenocarcinoma, Animals, Esophageal Neoplasms, Heterografts, Humans, Mice, Mice, Nude, Xenograft Model Antitumor Assays, PDOX, patient-derived orthotopic xenograft, gastro-esophageal junction, adenocarcinoma, carcinoembryonic-antigen-related cell adhesion, fluorescent antibodies, gastro – esophageal junction, Clinical Sciences, Oncology & Carcinogenesis
Abstract

Background/aimDuring surgical resection of gastroesophageal-junction (GEJ) adenocarcinoma, the margin status is often difficult to visualize resulting in high recurrence rates. The aim of the present study was to develop a labelling technique that would allow improved visualization of GEJ tumor margins for surgeons to reduce recurrence rates in a patient-like model.Materials and methodsA patient GEJ tumor was obtained from an endoscopic biopsy and implanted subcutaneously in a nude mouse. A patient-derived orthotopic xenograft (PDOX) model was established by implanting tumor fragments grown from a subcutaneous model to the cardia of the stomach of nude mice. CC1/3/5-SAB, an antibody to carcinoembryonic-antigen-related cell-adhesion molecules, was conjugated with infrared dye IRDye800 to create SAB-IR800. Forty-eight hours after i.v. injection of SAB-IR800, GEJ-PDOX mice were imaged.ResultsFluorescence imaging with SAB-IR800 brightly visualized the GEJ adenocarcinoma demonstrating specific targeting. In the PDOX model, injection of SAB-IR800 (50 μg) resulted in a tumor to background ratio of 1.78 at 48 hours and 1.86 at 72 hours.ConclusionPDOX models of GEJ tumors can be established from patients by endoscopic biopsy without undergoing surgical resection. GEJ PDOX models should be useful for developing novel diagnostics and therapeutics for this recalcitrant disease.

Published
2021

31. The Use of Fluorescent Anti-CEA Antibodies to Label, Resect and Treat Cancers: A Review

Author

Turner, Michael A, Lwin, Thinzar M, Amirfakhri, Siamak, Nishino, Hiroto, Hoffman, Robert M, Yazaki, Paul J, and Bouvet, Michael

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Digestive Diseases, Bioengineering, Cancer, Prevention, Biotechnology, Pancreatic Cancer, Colo-Rectal Cancer, Antibodies, Monoclonal, Carcinoembryonic Antigen, Fluorescent Dyes, GPI-Linked Proteins, Optical Imaging, carcinoembryonic antigen, CEA, fluorescence-guided surgery, FGS, infrared dyes, fluorescence, fluorescence labeling, Biochemistry and Cell Biology, Biochemistry and cell biology, Bioinformatics and computational biology, Medical biotechnology
Abstract

A major barrier to the diagnosis and effective treatment of solid-tumor cancers is the difficulty in detection and visualization of tumor margins in primary and metastatic disease. The use of fluorescence can augment the surgeon's ability to detect cancer and aid in its resection. Several cancer types express carcinoembryonic antigen (CEA) including colorectal, pancreatic and gastric cancer. Antibodies to CEA have been developed and tagged with near-infrared fluorescent dyes. This review article surveyed the use of CEA antibodies conjugated to fluorescent probes for in vivo studies since 1990. PubMed and Google Scholar databases were queried, and 900 titles and abstracts were screened. Fifty-nine entries were identified as possibly meeting inclusion/exclusion criteria and were reviewed in full. Forty articles were included in the review and their citations were screened for additional entries. A total of 44 articles were included in the final review. The use of fluorescent anti-CEA antibodies has been shown to improve detection and resection of tumors in both murine models and clinically. The cumulative results indicate that fluorescent-conjugated anti-CEA antibodies have important potential to improve cancer diagnosis and surgery. In an emerging technology, anti-CEA fluorescent antibodies have also been successfully used for photoimmunotherapy treatment for cancer.

Published
2021

32. Author Correction: Genotyping, sequencing and analysis of 140,000 adults from Mexico City

Author

Ziyatdinov, Andrey, Torres, Jason, Alegre-Díaz, Jesús, Backman, Joshua, Mbatchou, Joelle, Turner, Michael, Gaynor, Sheila M., Joseph, Tyler, Zou, Yuxin, Liu, Daren, Wade, Rachel, Staples, Jeffrey, Panea, Razvan, Popov, Alex, Bai, Xiaodong, Balasubramanian, Suganthi, Habegger, Lukas, Lanche, Rouel, Lopez, Alex, Maxwell, Evan, Jones, Marcus, García-Ortiz, Humberto, Ramirez-Reyes, Raul, Santacruz-Benítez, Rogelio, Nag, Abhishek, Smith, Katherine R., Damask, Amy, Lin, Nan, Paulding, Charles, Reppell, Mark, Zöllner, Sebastian, Jorgenson, Eric, Salerno, William, Petrovski, Slavé, Overton, John, Reid, Jeffrey, Thornton, Timothy A., Abecasis, Gonçalo, Berumen, Jaime, Orozco-Orozco, Lorena, Collins, Rory, Baras, Aris, Hill, Michael R., Emberson, Jonathan R., Marchini, Jonathan, Kuri-Morales, Pablo, and Tapia-Conyer, Roberto

Published
2024
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33. Nektar++: enhancing the capability and application of high-fidelity spectral/$hp$ element methods

Author

Moxey, David, Cantwell, Chris D., Bao, Yan, Cassinelli, Andrea, Castiglioni, Giacomo, Chun, Sehun, Juda, Emilia, Kazemi, Ehsan, Lackhove, Kilian, Marcon, Julian, Mengaldo, Gianmarco, Serson, Douglas, Turner, Michael, Xu, Hui, Peiró, Joaquim, Kirby, Robert M., and Sherwin, Spencer J.

Subjects
Computer Science - Mathematical Software, Mathematics - Numerical Analysis, Physics - Fluid Dynamics
Abstract

Nektar++ is an open-source framework that provides a flexible, high-performance and scalable platform for the development of solvers for partial differential equations using the high-order spectral/$hp$ element method. In particular, Nektar++ aims to overcome the complex implementation challenges that are often associated with high-order methods, thereby allowing them to be more readily used in a wide range of application areas. In this paper, we present the algorithmic, implementation and application developments associated with our Nektar++ version 5.0 release. We describe some of the key software and performance developments, including our strategies on parallel I/O, on in situ processing, the use of collective operations for exploiting current and emerging hardware, and interfaces to enable multi-solver coupling. Furthermore, we provide details on a newly developed Python interface that enables a more rapid introduction for new users unfamiliar with spectral/$hp$ element methods, C++ and/or Nektar++. This release also incorporates a number of numerical method developments - in particular: the method of moving frames, which provides an additional approach for the simulation of equations on embedded curvilinear manifolds and domains; a means of handling spatially variable polynomial order; and a novel technique for quasi-3D simulations to permit spatially-varying perturbations to the geometry in the homogeneous direction. Finally, we demonstrate the new application-level features provided in this release, namely: a facility for generating high-order curvilinear meshes called NekMesh; a novel new AcousticSolver for aeroacoustic problems; our development of a 'thick' strip model for the modelling of fluid-structure interaction problems in the context of vortex-induced vibrations. We conclude by commenting some directions for future code development and expansion., Comment: 21 pages, 14 figures

Published
2019
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34. Diffusion-limited Relic Particle Production

Author

Scherrer, Robert J. and Turner, Michael S.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics, High Energy Physics - Phenomenology
Abstract

We examine the thermal evolution of particle number densities in the early universe when the particles have a finite diffusion length. Assuming that annihilations are impossible when the mean separation of the particles is larger than their diffusion length, we derive a version of the Boltzmann equation for freeze out in this scenario and an approximate solution, accurate to better than 2\%. The effect of a finite diffusion length is to increase the final relic freeze-out abundance over its corresponding value when diffusion effects are ignored. When diffusion is limited only by scattering off of the thermal background, and the annihilation cross section is bounded by unitarity, a significant effect on the freeze-out abundance requires a scattering cross section much larger than the annihilation cross section. A similar effect is demonstrated when the relic particles are produced via the freeze-in mechanism, but in this case the finite diffusion length is due to the scattering of particles that annihilate into the relic particle of interest. For freeze in, the effect of a finite diffusion length is to reduce the final relic particle abundance. The effects of a finite diffusion length are most important when the scattering cross section or the relic mass are very large. While we have not found a particularly compelling example where this would affect previous results, with the current interest in new dark matter candidates it could become an important consideration., Comment: 10 pages, 3 figures, discussion generalized to p-wave and higher-order annihilations, references added

Published
2019
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35. High-order curvilinear hybrid mesh generation for CFD simulations

Author

Marcon, Julian, Turner, Michael, Peiró, Joaquim, Moxey, David, Pollard, Claire R., Bucklow, Henry, and Gammon, Mark

Subjects
Computer Science - Graphics, Computer Science - Computational Geometry, Physics - Computational Physics, Physics - Fluid Dynamics
Abstract

We describe a semi-structured method for the generation of high-order hybrid meshes suited for the simulation of high Reynolds number flows. This is achieved through the use of highly stretched elements in the viscous boundary layers near the wall surfaces. CADfix is used to first repair any possible defects in the CAD geometry and then generate a medial object based decomposition of the domain that wraps the wall boundaries with partitions suitable for the generation of either prismatic or hexahedral elements. The latter is a novel distinctive feature of the method that permits to obtain well-shaped hexahedral meshes at corners or junctions in the boundary layer. The medial object approach allows greater control on the "thickness" of the boundary-layer mesh than is generally achievable with advancing layer techniques. CADfix subsequently generates a hybrid straight sided mesh of prismatic and hexahedral elements in the near-field region modelling the boundary layer, and tetrahedral elements in the far-field region covering the rest of the domain. The mesh in the near-field region provides a framework that facilitates the generation, via an isoparametric technique, of layers of highly stretched elements with a distribution of points in the direction normal to the wall tailored to efficiently and accurately capture the flow in the boundary layer. The final step is the generation of a high-order mesh using NekMesh, a high-order mesh generator within the Nektar++ framework. NekMesh uses the CADfix API as a geometry engine that handles all the geometrical queries to the CAD geometry required during the high-order mesh generation process. We will describe in some detail the methodology using a simple geometry, a NACA wing tip, for illustrative purposes. Finally, we will present two examples of application to reasonably complex geometries proposed by NASA as CFD validation cases., Comment: Pre-print accepted to the 2018 AIAA Aerospace Sciences Meeting

Published
2019
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36. A variational approach to high-order r-adaptation

Author

Marcon, Julian, Turner, Michael, Moxey, David, Sherwin, Spencer J., and Peiró, Joaquim

Subjects
Computer Science - Computational Geometry, Physics - Computational Physics
Abstract

A variational framework, initially developed for high-order mesh optimisation, is being extended for r-adaptation. The method is based on the minimisation of a functional of the mesh deformation. To achieve adaptation, elements of the initial mesh are manipulated using metric tensors to obtain target elements. The nonlinear optimisation in turns adapts the final high-order mesh to best fit the description of the target elements by minimising the element distortion. Encouraging preliminary results prove that the method behaves well and can be used in the future for more extensive work which shall include the use of error indicators from CFD simulations., Comment: Pre-print accepted to the 26th International Meshing Roundtable

Published
2019

37. Humanized Fluorescent Tumor-associated Glycoprotein-72 Antibody Selectively Labels Colon-cancer Liver Metastases in Orthotopic Mouse Models

Author

HOLLANDSWORTH, HANNAH M, NISHINO, HIROTO, TURNER, MICHAEL, AMIRFAKHRI, SIAMAK, FILEMONI, FILEMONI, HOFFMAN, ROBERT M, YAZAKI, PAUL J, and BOUVET, MICHAEL

Subjects
Rare Diseases, Liver Disease, Colo-Rectal Cancer, Digestive Diseases, Cancer, Aetiology, 2.1 Biological and endogenous factors, Animals, Antigens, Neoplasm, Colon, Fluorescent Dyes, Liver Neoplasms, Mice, Mice, Nude, Optical Imaging, TAG-72, fluorescent antibody, colorectal cancer orthotopic, liver metastasis, nude mice, infrared fluorescence imaging, fluorescence-guided surgery, Clinical Sciences, Oncology & Carcinogenesis
Abstract

Background/aimFluorescence imaging has been shown to improve intra-operative detection of liver metastasis. The present study aimed to determine whether humanized anti-TAG-72 antibody (huCC49) conjugated to a near-infrared dye provides selective labeling of colorectal-cancer liver metastasis in orthotopic mouse models.Materials and methodsHumanized anti-TAG-72 (huCC49) was conjugated to IRDye800CW (huCC49-IR800). Orthotopic liver-metastasis nude-mouse models (n=5) were established with the human colon-cancer LS174T cell-line. Three weeks later, mice were administered huCC49-IR800 and intra-vital imaging was performed 48 h later. The mean tumor-to-liver ratio (TLR) was calculated.ResultsIntra-vital imaging demonstrated clear tumor margins with minimal liver fluorescence 48 h after administration of 50 μg huCC49-IR800 with mean TLR=7.53 (SD±2.76).ConclusionAnti-TAG-72 monoclonal antibody conjugated to IRDye800 provides distinct and bright labeling of colorectal tumors in orthotopic nude-mouse models of liver metastasis. TAG-72 may be a useful target for intra-operative imaging of colorectal cancer liver metastasis in the clinic.

Published
2020

38. Three-dimensional geometry inference of convex and non-convex rooms using spatial room impulse responses

Author

Lovedee-Turner, Michael and Murphy, Damian

Subjects
621.3
Abstract

This thesis presents research focused on the problem of geometry inference for both convex- and non-convex-shaped rooms, through the analysis of spatial room impulse responses. Current geometry inference methods are only applicable to convex-shaped rooms, requiring between 6--78 discretely spaced measurement positions, and are only accurate under certain conditions, such as a first-order reflection for each boundary being identifiable across all, or some subset of, these measurements. This thesis proposes that by using compact microphone arrays capable of capturing spatiotemporal information, boundary locations, and hence room shape for both convex and non-convex cases, can be inferred, using only a sufficient number of measurement positions to ensure each boundary has a first-order reflection attributable to, and identifiable in, at least one measurement. To support this, three research areas are explored. Firstly, the accuracy of direction-of-arrival estimation for reflections in binaural room impulse responses is explored, using a state-of-the-art methodology based on binaural model fronted neural networks. This establishes whether a two-microphone array can produce accurate enough direction-of-arrival estimates for geometry inference. Secondly, a spherical microphone array based spatiotemporal decomposition workflow for analysing reflections in room impulse responses is explored. This establishes that simultaneously arriving reflections can be individually detected, relaxing constraints on measurement positions. Finally, a geometry inference method applicable to both convex and more complex non-convex shaped rooms is proposed. Therefore, this research expands the possible scenarios in which geometry inference can be successfully applied at a level of accuracy comparable to existing work, through the use of commonly used compact microphone arrays. Based on these results, future improvements to this approach are presented and discussed in detail.

Published
2019

39. Nuclear Kinetic Equilibrium During Big Bang Nucleosynthesis

Author

McDermott, Samuel D. and Turner, Michael S.

Subjects
High Energy Physics - Phenomenology, Astrophysics - Cosmology and Nongalactic Astrophysics, Astrophysics - High Energy Astrophysical Phenomena
Abstract

Sasankan et al, have recently claimed that there are significant deviations in the phase-space distributions of the kinetic energies of nuclei from the Maxwell-Boltzmann form usually assumed in BBN, and further, that these deviations lead to big changes in the predicted light-element abundances. Solving the relativistic Boltzmann equation perturbatively, we explicitly show that these deviations are not 20% as claimed, but rather are about 10^-17 in size and hence cannot significantly alter the predicted light-element abundances. We discuss and compute two related effects: O(0.1%) corrections to the kinetic distributions of nuclei that arise from small relativistic corrections to the MB distribution and a much smaller effect, nuclear kinetic drag, which arises from the heat transferred from the EM plasma to nuclei that is needed to maintain kinetic equilibrium., Comment: 10 pages, extended comparison to Sasankan et al

Published
2018

40. Dibaryons cannot be the dark matter

Author

Kolb, Edward W. and Turner, Michael S.

Subjects
High Energy Physics - Phenomenology, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

The hypothetical $SU(3)$ flavor-singlet dibaryon state $S$ with strangeness $-2$ has been discussed as a dark-matter candidate capable of explaining the curious 5-to-1 ratio of the mass density of dark matter to that of baryons. We study the early-universe production of dibaryons and find that irrespective of the hadron abundances produced by the QCD quark/hadron transition, rapid particle reactions thermalized the $S$ abundance, and it tracked equilibrium until it "froze out" at a tiny value. For the plausible range of dibaryon masses (1860 - 1890 MeV) and generous assumptions about its interaction cross sections, $S$'s account for at most $10^{-11}$ of the baryon number, and thus cannot be the dark matter. Although it is not the dark matter, if the $S$ exists it might be an interesting relic., Comment: 11 pages, 5 figures

Published
2018
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42. High-order mesh generation for CFD solvers

Author

Turner, Michael and Peiro, Joaquim

Subjects
629.13
Abstract

The generation of curvilinear, high-order meshes for CFD applications remains a significant bottleneck in the progress and application of high-order CFD methods. These methods have superior numerical accuracy over low-order methods due to their use of piecewise polynomial representations of domains and solutions. As such they are viewed as a potential source of higher fidelity simulations with a view of industrial application [81]. The current state of the art in high-order mesh generation does not provide a reliable and efficient approach which would be required in an industrial setting. This thesis investigates the generation of high-order curvilinear meshes for CFD applications. It focuses around the design and algorithms of an open-source high- order mesh generator, NekMesh, which has been created as part of this project and is part of the Nektar++ high-order CFD suite. The program aims to create high-order meshes directly from CAD as automatically and robustly as possible. This means that all parts of the high-order meshing problem must be addressed including CAD handling and linear mesh generation. A significant contribution of this thesis to high-order mesh generation is the work on a variational approach to the generation of curved meshes. This has been encompassed in a framework within NekMesh. It has been shown to be able to apply several high-order mesh generation methods found throughout the literature and unify them in one context. In addition to this the algorithms used within this framework mitigate a significant amount of the high computational cost associated with high-order mesh generation and attempts to address robustness issues. In addition to the work on NekMesh this thesis also explores using a semi- structured approach to linear mesh generation which can address several robustness issues. It also applies several the methods created to industrially relevant examples.

Published
2018
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43. KUNAPIPI GARDENS: TRANSFER PRICING IN THE SERVICE INDUSTRY: The CEO of a resort hotel wants a new income statement format to better capture and understand the company's performance

Author

Hesford, James W., Turner, Michael James, and Thomas, Charles R., Jr.

Subjects
Services industry -- Service enhancement, Chief executive officers -- Powers and duties, Transfer pricing -- Methods, Banking, finance and accounting industries, Business, general, Business
Abstract

The Student Case Competition is sponsored annually by IMA[R] to provide an opportunity for students to interpret, analyze, evaluate, synthesize, and communicate a solution to a management accounting problem. About [...]

Published
2022

47. Time for a Western Australian 'Group of Three'?: A Speculative Essay

Author

Turner, Michael and Brown, Alistair

Abstract

This study analyses the theoretical cost-savings that might flow from a merger of three of Western Australia's five universities. The results of the study show that an amalgamation would not only reduce costs of operation, but also improve non-current asset use and accountability. Combination reporting also allows the key stakeholders to appraise these universities' main financial activities, which appear to be maintaining a relatively high level of non-salary expenditure as a percentage of revenue and preserving a very high percentage of land and buildings as mainstay assets.

Published
2015

48. A systematic review of potential long-term effects of sport-related concussion

Author

Manley, Geoff, Gardner, Andrew J, Schneider, Kathryn J, Guskiewicz, Kevin M, Bailes, Julian, Cantu, Robert C, Castellani, Rudolph J, Turner, Michael, Jordan, Barry D, Randolph, Christopher, Dvořák, Jiří, Hayden, K Alix, Tator, Charles H, McCrory, Paul, and Iverson, Grant L

Subjects
Health Services and Systems, Health Sciences, Psychology, Brain Disorders, Mind and Body, Acquired Cognitive Impairment, Behavioral and Social Science, Traumatic Brain Injury (TBI), Neurosciences, Physical Injury - Accidents and Adverse Effects, Mental Health, Depression, Basic Behavioral and Social Science, Traumatic Head and Spine Injury, Aetiology, 6.6 Psychological and behavioural, Evaluation of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, Neurological, Mental health, Good Health and Well Being, Athletes, Athletic Injuries, Brain, Brain Concussion, Cognition Disorders, Football, Humans, Incidence, Neuroimaging, Post-Concussion Syndrome, Risk Factors, Engineering, Medical and Health Sciences, Education, Sport Sciences, Clinical sciences, Sports science and exercise, Applied and developmental psychology
Abstract

ObjectiveSystematic review of possible long-term effects of sports-related concussion in retired athletes.Data sourcesTen electronic databases.Study selectionOriginal research; incidence, risk factors or causation related to long-term mental health or neurological problems; individuals who have suffered a concussion; retired athletes as the subjects and possible long-term sequelae defined as >10 years after the injury.Data extractionStudy population, exposure/outcome measures, clinical data, neurological examination findings, cognitive assessment, neuroimaging findings and neuropathology results. Risk of bias and level of evidence were evaluated by two authors.ResultsFollowing review of 3819 studies, 47 met inclusion criteria. Some former athletes have depression and cognitive deficits later in life, and there is an association between these deficits and multiple prior concussions. Former athletes are not at increased risk for death by suicide (two studies). Former high school American football players do not appear to be at increased risk for later life neurodegenerative diseases (two studies). Some retired professional American football players may be at increased risk for diminishment in cognitive functioning or mild cognitive impairment (several studies), and neurodegenerative diseases (one study). Neuroimaging studies show modest evidence of macrostructural, microstructural, functional and neurochemical changes in some athletes.ConclusionMultiple concussions appear to be a risk factor for cognitive impairment and mental health problems in some individuals. More research is needed to better understand the prevalence of chronic traumatic encephalopathy and other neurological conditions and diseases, and the extent to which they are related to concussions and/or repetitive neurotrauma sustained in sports.

Published
2017

50. Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease: Insights From the ISCHEMIA Trial

Author

Reynolds, Harmony R., primary, Cyr, Derek D., additional, Merz, C. Noel Bairey, additional, Shaw, Leslee J., additional, Chaitman, Bernard R., additional, Boden, William E., additional, Alexander, Karen P., additional, Rosenberg, Yves D., additional, Bangalore, Sripal, additional, Stone, Gregg W., additional, Held, Claes, additional, Spertus, John, additional, Goetschalckx, Kaatje, additional, Bockeria, Olga, additional, Newman, Jonathan D., additional, Berger, Jeffrey S., additional, Elghamaz, Ahmed, additional, Lopes, Renato D., additional, Min, James K., additional, Berman, Daniel S., additional, Picard, Michael H., additional, Kwong, Raymond Y., additional, Harrington, Robert A., additional, Thomas, Boban, additional, O'Brien, Sean M., additional, Maron, David J., additional, Hochman, Judith S., additional, Mavromatis, Kreton, additional, Linefsky, Jason, additional, Miller, Todd, additional, Banerjee, Subhash, additional, Reynolds, Harmony R., additional, Donnino, Robert M., additional, Phillips, Lawrence M., additional, Saric, Muhamed, additional, Abdul‐Nour, Khaled, additional, Stone, Peter H., additional, Jang, James J., additional, Yee, Gennie, additional, Weitz, Steven, additional, Arnold, Suzanne, additional, O’Keefe, James Henry, additional, Shapiro, Michael D., additional, El‐Hajjar, Mohammad, additional, Sidhu, Mandeep S., additional, Fein, Steven A., additional, Torosoff, Mikhail T., additional, Lyubarova, Radmila, additional, Mookherjee, Sulagna, additional, Drzymalski, Krzysztof, additional, McFalls, Edward O., additional, Garcia, Santiago A., additional, Bertog, Stefan C., additional, Siddiqui, Rizwan A., additional, Ishani, Areef, additional, Hansen, Ronnell A., additional, Khouri, Michel Georges, additional, Goldberg, Jonathan L., additional, Goldweit, Richard, additional, Cohen, Ronny A., additional, Mirrer, Brooks, additional, Navarro, Victor, additional, Winchester, David E., additional, Kronenberg, Marvin, additional, Rogal, Philip, additional, McFarren, Christopher, additional, Heitner, John F., additional, Dauber, Ira M., additional, Cannan, Charles, additional, Sudarshan, Sriram, additional, Mehta, Puja K., additional, McDaniel, Michael, additional, Lerakis, Stamatios, additional, Quyyumi, Arshed, additional, Wenger, Nanette K., additional, Hedgepeth, Chester M., additional, Hurlburt, Heather, additional, Rosen, Alan, additional, Sahul, Zakir, additional, Booth, David, additional, Leung, Steve, additional, Abdel‐Latif, Ahmed, additional, Reda, Hassan, additional, Ziada, Khaled, additional, Setty, Sampoornima, additional, Barua, Rajat S., additional, Hage, Fadi, additional, Caldeira, Christiano, additional, Davies, James E., additional, Leesar, Massoud, additional, Heo, Jaekyeong, additional, Iskandrian, Amy, additional, Al Solaiman, Firas, additional, Singh, Satinder, additional, Dajani, Khaled, additional, Der Mesropian, Paul, additional, Sacco, Joseph, additional, McCandless, Brian, additional, Orgera, Marisa, additional, Arif, Imran, additional, Kerr, Hanan, additional, Trejo (Gutierrez), Jorge F., additional, Fletcher, Gerald, additional, Lane, Gary E., additional, Neeson, Lynn M., additional, Parikh, Pragnesh P., additional, Pollak, Peter M., additional, Shapiro, Brian P., additional, Landolfo, Kevin, additional, Gemignani, Anthony, additional, O’Rourke, Daniel, additional, Meadows, Judith L., additional, Call, Jason T., additional, Hannan, Joseph, additional, Bojar, Robert, additional, Kumar, Deepti, additional, Mukai, John, additional, Martin, Edward T., additional, Vorobiof, Gabriel, additional, Moorman, Alec, additional, Kinlay, Scott, additional, Hamburger, Robert J., additional, Rocco, Thomas P., additional, Bhatt, Deepak L., additional, Croce, Kevin, additional, Quin, Jacquelyn A., additional, Anumpa, Jati, additional, Zenati, Marco, additional, Faxon, David P., additional, Rayos, Glenn, additional, Seedhom, Ashraf, additional, Sullenberger, Lance, additional, Kumkumian, Gregory, additional, Sedlis, Steven P., additional, Donnino, Robert M., additional, Lorin, Jeffrey, additional, Tamis‐Holland, Jacqueline E., additional, Kornberg, Robert, additional, Leber, Robert, additional, Saba, Souheil, additional, Lee, Michael W., additional, Small, Delano R., additional, Nona, Wassim, additional, Alexander, Patrick B., additional, Rehman, Iram, additional, Badami, Umesh, additional, Marzo, Kevin, additional, Robbins, Inga H., additional, Levite, Howard A., additional, Shetty, Sanjay, additional, Patel, Mayuri, additional, Hamroff, Glenn S., additional, Little, Raymond W., additional, Zimbelman, Brandi D., additional, Lui, Charles Y., additional, Smith, Brigham R., additional, Vezina, Daniel P., additional, Khor, Lillian L., additional, Abraham, Josephine D., additional, Bull, David A., additional, McKellar, Stephen H., additional, Kotter, John, additional, Hu, Bob, additional, Labovitz, Arthur J., additional, Berlowitz, Michael, additional, Matar, Fadi, additional, Rodriguez, Fatima, additional, Schnittger, Ingela, additional, Fearon, William F., additional, Deedwania, Prakash, additional, Reddy, Kiran, additional, Sweeny, Joseph, additional, Spizzieri, Christopher, additional, Hochberg, Claudia P., additional, Salerno, William D., additional, Wyman, Ray, additional, Zarka, Amer, additional, Shah, Anil V., additional, Haldis, Thomas, additional, Kohn, Jeffrey A., additional, Girotra, Saket, additional, Almousalli, Omar, additional, Krishnam, Mayil S., additional, Milliken, Jeffrey C., additional, Patel, Pranav M., additional, Seto, Arnold H., additional, Harley, Kevin T., additional, Gibson, Michael A., additional, Allen, Byron J., additional, Coram, Rita, additional, Thomas, Sabu, additional, Schwartz, Ronald G., additional, Chen, Wei, additional, El Shahawy, Mahfouz, additional, Stafford, James, additional, Abernethy, William B., additional, Zurick, Andrew, additional, Meyer, Thomas M., additional, Morford, Ronald G., additional, Rutkin, Bruce, additional, Bokhari, Sabahat, additional, Sokol, Seth I., additional, Meisner, Jay, additional, Hamzeh, Ihab, additional, Misra, Arunima, additional, Wall, Matthew, additional, De Rosen, Veronica Lenges, additional, Alam, Mahboob, additional, Turner, Michael C., additional, Mulhearn, Thomas J., additional, Good, Arnold P., additional, Shammas, Nicolas W., additional, Chilton, Robert, additional, Nguyen, Patricia K., additional, Jezior, Matthew, additional, Gordon, Paul C., additional, Crain, Thomas, additional, Stenberg, Robert, additional, Pedalino, Ronald P., additional, Wiesel, Joseph, additional, Juang, George J., additional, Al‐Amoodi, Mohammed, additional, Wohns, David, additional, Lader, Ellis W., additional, Mumma, Michael, additional, Dharmarajan, Lekshmi, additional, McGarvey, Joseph F. X., additional, Downes, Thomas R., additional, Luckasen, Gary J., additional, Cheong, Benjamin, additional, Potluri, Srinivasa, additional, Mastouri, Ronald A., additional, Breall, Jeffery A., additional, Revtyak, George E., additional, Bazeley, Jonathan W., additional, Li, Dayuan, additional, Giedd, Kenneth, additional, Old, Wayne, additional, Burt, Francis, additional, Sokhon, Kozhaya, additional, Gopal, Deepika, additional, Valeti, Uma S., additional, Kobashigawa, Jon, additional, Govindan, Sajeev Chakanalil, additional, Nair, Rajesh Gopalan, additional, Manjunath, Cholenahally Nanjappa, additional, Moorthy, Nagaraja, additional, Manjunath, Satvic Cholenahally, additional, Narayanappa, Suryaprakash, additional, Pandit, Neeraj, additional, Nath, Ranjit Kumar, additional, Dwivedi, S. K., additional, Narain, V. S., additional, Chandra, Sharad, additional, Wander, Gurpreet S., additional, Tandon, Rohit, additional, Ralhan, Sarju, additional, Aslam, Naved, additional, Goyal, Abhishek, additional, Bhargava, Balram, additional, Karthikeyan, G., additional, Ramakrishnan, S., additional, Seth, Sandeep, additional, Yadav, Rakesh, additional, Singh, Sandeep, additional, Roy, Ambuj, additional, Parakh, Neeraj, additional, Verma, Sunil Kumar, additional, Narang, Rajiv, additional, Mishra, Sundeep, additional, Naik, Nitish, additional, Sharma, Gautam, additional, Choudhary, Shiv Kumar, additional, Patel, Chetan, additional, Gulati, Gurpreet, additional, Sharma, Sanjeev, additional, Bahl, V. K., additional, Mathew, Anoop, additional, Punnoose, Eapen, additional, Gadkari, Milind Avdhoot, additional, Gadage, Siddharth, additional, Pillay, Tapan Umesh, additional, Satheesh, Santhosh, additional, Mathur, Atul, additional, Kaul, Upendra, additional, Christopher, Johann, additional, Menon, Rajeev, additional, Kumar, Nirmal, additional, Oomman, Abraham, additional, Mao, Robert, additional, Solomon, Hilda, additional, Naik, Sudhir, additional, Khan, Sajeeda Parveen, additional, Grant, Purvez, additional, Kachru, Ranjan, additional, Ajit Kumar, V. K., additional, Ganapathi, Sanjay, additional, Jayakumar, K., additional, Sivadasanpillai, Harikrishnan, additional, Sasidharan, Bijulal, additional, Kapilamoorthy, T. R., additional, Polamuri, Praneeth, additional, Senior, Roxy, additional, Gurunathan, Sothinathan, additional, Karogiannis, Nikolaos, additional, Shah, Benoy N., additional, Trimlett, Richard HJ, additional, Rubens, Michael B., additional, Nicol, Edward D., additional, Mittal, Tarun K., additional, Hampson, Reinette, additional, Gamma, Reto Andreas, additional, de Belder, Mark A., additional, Thambyrajah, Jeet, additional, Nageh, Thuraia, additional, Davies, John R., additional, Lindsay, Steven J., additional, Kurian, John, additional, Jamil, Haqeel, additional, Raheem, Osama, additional, Hoye, Angela, additional, Donnelly, Patrick, additional, Valecka, Bernardas, additional, Chauhan, Anoop, additional, Barr, Craig, additional, Alfakih, Khaled, additional, Byrne, Jonathan, additional, Webb, Ian, additional, Henriksen, Peter, additional, OKane, Peter, additional, de Silva, Ramesh, additional, Conway, Dwayne S. G., additional, Sirker, Alexander A, additional, Hoole, Stephen P., additional, Witherow, Fraser N., additional, Johnston, Nicola, additional, Harbinson, Mark, additional, Walsh, Simon, additional, Douglas, Hanna, additional, Luckie, Matthew, additional, Sobolewska, Jolanta, additional, Jeetley, Paramjit, additional, Patel, Niket, additional, Kotecha, Tushar, additional, Travill, Christopher, additional, Karimullah, Iqbal, additional, Al‐Bustami, Mahmud, additional, Braganza, Denise, additional, Henderson, Robert, additional, Pointon, Kate, additional, Naik, Surendra, additional, Mathew, Thomas, additional, Berry, Colin, additional, Collison, Damien, additional, Roditi, Giles, additional, Moriarty, Andrew J., additional, Glover, Jason D., additional, Pradhan, Jiwan, additional, Mikhail, Ghada, additional, Francis, Darrel P., additional, Gosselin, Gilbert, additional, Diaz, Ariel, additional, Rheault, Philippe, additional, Barrero, Miguel, additional, Gagné, Carl‐Éric, additional, Pépin‐Dubois, Yanek, additional, Costa, Ricardo, additional, Sia, Ying Tung, additional, Lemay, Catherine, additional, Gisbert, Alejandro, additional, Gervais, Pierre, additional, Rheault, Alain, additional, Phaneuf, Denis Carl, additional, Garg, Pallav, additional, Chow, Benjamin J. W., additional, Hessian, Renee C., additional, Beanlands, Rob S., additional, Davies, Richard F., additional, Bainey, Kevin R., additional, Cheema, Asim N., additional, Bagai, Akshay, additional, Wald, Ron, additional, Goodman, Shaun, additional, Graham, John Joseph, additional, Peterson, Mark, additional, Chow, Chi‐Ming, additional, Abramson, Beth, additional, Cheema, Asim Nazir, additional, Vakani, Mohammad Tariq, additional, Cha, James, additional, Howarth, Andrew G, additional, Wong, Graham, additional, Uxa, Amar, additional, Galiwango, Paul, additional, Kassam, Saleem, additional, Mukherjee, Ashok, additional, Ricci, A. Joseph, additional, Lam, Andy, additional, Mehta, Shamir, additional, Udell, Jacob, additional, Généreux, Philippe, additional, Hameed, Adnan, additional, Daba, Ledjalem, additional, Hueb, Whady, additional, Rezende, Paulo Cury, additional, Silva, Expedito Eustáquio Ribeiro, additional, Hueb, Alexandre Ciappina, additional, Smanio, Paola Emanuela Poggio, additional, de Quadros, Alexandre Schaan, additional, Kalil, Renato Abdala Karam, additional, da Costa Vieira, José Luiz, additional, Grossmann, Gabriel, additional, de Oliveira, Pedro Píccaro, additional, Bridi, Leonardo, additional, Savaris, Simone, additional, Vitola, João V., additional, Cerci, Rodrigo J., additional, Farias, Fabio R., additional, Fernandes, Miguel M., additional, Marin‐Neto, José Antonio, additional, Schmidt, André, additional, de Oliveira Lima Filho, Moysés, additional, Oliveira, Ricardo Mendes, additional, Chierice, João Reynaldo Abbud, additional, Polanczyk, Carísi A., additional, Furtado, Mariana V., additional, Smidt, Luis F., additional, Carvalho, Antonio Carlos, additional, Pucci, Gustavo, additional, Lyra, Flavio, additional, Junior, Alvaro Rabelo Alves, additional, Dracoulakis, Marianna D. A., additional, Lima, Rodolfo G. S. D, additional, Figueiredo, Estevao, additional, Caramori, Paulo Ricardo, additional, Tumelero, Rogerio, additional, Dall’Orto, Frederico, additional, Mesquita, Claudio T., additional, Colafranseschi, Alexandre S., additional, Oliveira, Amarino C., additional, Carvalho, Luiz A., additional, Palazzo, Isabella C., additional, Sousa, Andre S., additional, da Silva, Expedito Eustáquio Ribeiro, additional, de Barros, Pedro Gabriel Melo, additional, de Pádua Silva Baptista, Luciana, additional, Rodrigues, Marcelo Jamus, additional, de Resende, Marcos Valério Coimbra, additional, Saraiva, Jose Francisco, additional, Costantini, Costantino, additional, Demkow, Marcin, additional, Pracon, Radoslaw, additional, Kepka, Cezary, additional, Teresinska, Anna, additional, Kryczka, Karolina, additional, Henzel, Jan, additional, Solecki, Mateusz, additional, Kaczmarska, Edyta, additional, Mazurek, Tomasz, additional, Drozdz, Jaroslaw, additional, Czarniak, Bartosz, additional, Frach, Malgorzata, additional, Szymczyk, Konrad, additional, Niedzwiecka, Iwona, additional, Sobczak, Sebastian, additional, Ciurus, Tomasz, additional, Jakubowski, Piotr, additional, Misztal‐Teodorczyk, Magdalena, additional, Teodorczyk, Dawid, additional, Fratczak, Aleksandra, additional, Szkopiak, Marcin, additional, Lebioda, Patrycja, additional, Wlodarczyk, Michal, additional, Plachcinska, Anna, additional, Kusmierek, Jacek, additional, Miller, Magdalena, additional, Marciniak, Halina, additional, Wojtczak‐Soska, Karolina, additional, Luczak, Katarzyna, additional, Tarchalski, Tomasz, additional, Cichocka‐Radwan, Anna, additional, Szwed, Hanna, additional, Szulczyk, Grazyna Anna, additional, Witkowski, Adam, additional, Kukula, Krzysztof, additional, Celinska‐Spodar, Malgorzta, additional, Zalewska, Joanna, additional, Gajos, Grzegorz, additional, Bury, Krzysztof, additional, Pruszczyk, Piotr, additional, Roik, Marek, additional, Loboz‐Grudzien, Krystyna, additional, Sokalski, Leszek, additional, Brzezinska, Barbara, additional, Lesiak, Maciej, additional, Lanocha, Magdalena, additional, Reczuch, Krzysztof W., additional, Kalarus, Zbigniew, additional, Swiatkowski, Andrzej, additional, Szulik, Mariola, additional, Musial, Wlodzimierz J., additional, Bockeria, Leo, additional, Petrosyan, Karen, additional, Trifonova, Tatiana, additional, Chernyavskiy, Alexander M., additional, Kretov, Evgeniy I., additional, Grazhdankin, Igor O., additional, Bershtein, Leonid L., additional, Sayganov, Sergey A., additional, Kuzmina‐Krutetskaya, Anastasia M., additional, Zbyshevskaya, Elizaveta V., additional, Katamadze, Nana O., additional, Demchenko, Elena A., additional, Kozlov, Pavel S., additional, Kozulin, Vikentiy Y., additional, Lubinskaya, Ekaterina I., additional, Lopez‐Sendon, Jose, additional, Castro, Almudena, additional, Salicio, Elena Refoyo, additional, Guzman, Gabriela, additional, Galeote, Gabriel, additional, Valbuena, Silvia, additional, Peteiro, Jesús, additional, Martínez‐Ruíz, María Dolores, additional, Pérez‐Fernández, Ruth, additional, Cuenca‐Castillo, José J., additional, Flores‐Ríos, Xacobe, additional, Prada‐Delgado, Óscar, additional, Barge‐Caballero, Gonzalo, additional, Juanatey, Jose Ramon Gonzalez, additional, Bayarri, Miguel Souto, additional, Nuñez, Virginia Pubull, additional, Sanchez, Raymundo Ocaranza, additional, Alvarez, Belen Cid, additional, Gil, Carlos Peña, additional, Monzonis, Amparo Martinez, additional, Sionis, Alessandro, additional, Perales, Montserrat Vila, additional, Padró, Josep Maria, additional, Peñaranda, Antonio Serra, additional, Picart, Joan García, additional, Iglesias, Antonino Ginel, additional, Marimon, Xavier Garcia‐Moll, additional, Lladó, Guillem Pons, additional, Costa, Francesc Carreras, additional, Miro, Vicente, additional, Diez, Jose L., additional, Calvillo, Pilar, additional, Ortuño, F. Marin, additional, Chávarri, M. Valdés, additional, Montolliu, A. Tello, additional, Bermudez, E. Pinar, additional, De La Morena, G., additional, Blancas, Montserrat Gracida, additional, Luena, Jose Enrique Castillo, additional, Fernandez‐Aviles, Francisco, additional, Chen, Jiyan, additional, Wu, Yongjian, additional, Ma, Yitong, additional, Yang, Yining, additional, Ji, Zheng, additional, Yang, Xinchun, additional, Lin, Wenhua, additional, Zeng, Hesong, additional, Fu, Xin, additional, Yang, Bin, additional, Wang, Songtao, additional, Cheng, Gong, additional, Zhao, Yulan, additional, Fang, Xuehua, additional, Zeng, Qiutang, additional, Su, Xi, additional, Li, Qingxian, additional, Nie, Shao‐ping, additional, Yu, Qin, additional, Wang, Jian’an, additional, Zhang, Shuyang, additional, Liu, Zhenyu, additional, Perna, Gian Piero, additional, Marini, Marco, additional, Gabrielli, Gabriele, additional, Provasoli, Stefano, additional, Verna, Edoardo, additional, Monti, Lorenzo, additional, Nardi, Barbara, additional, Di Chiara, Antonio, additional, Mortara, Andrea, additional, Galvani, Marcello, additional, Ottani, Filippo, additional, Sicuro, Marco, additional, Calabro, Paolo, additional, Formisano, Tiziana, additional, Tarantini, Giuseppe, additional, Cucchini, Umberto, additional, Andres, Anto Luigi, additional, Racca, Emanuela, additional, Briguori, Carlo, additional, Amati, Roberto, additional, Vergoni, William, additional, Russo, Aldo, additional, Fanelli, Raffaele, additional, Poh, Kian‐Keong, additional, Chai, Ping, additional, Lau, Titus, additional, Loh, Joshua P., additional, Tay, Edgar L., additional, Teoh, Kristine, additional, Teo, Lynette L., additional, Ong, Ching‐Ching, additional, Wong, Raymond C., additional, Loh, Poay‐Huan, additional, Kofidis, Theodoros, additional, Chan, Wan Xian, additional, Chan, Koo Hui, additional, Foo, David, additional, Kong, Jason Loh Kwok, additional, Er, Ching Min, additional, Jafary, Fahim Haider, additional, Chua, Terrance, additional, Doerr, Rolf, additional, Stumpf, Juergen, additional, Matschke, Klaus, additional, Simonis, Gregor, additional, Kadalie, Clemens T., additional, Sechtem, Udo, additional, Ong, Peter, additional, Schulze, P. Christian, additional, Goebel, Bjoern, additional, Lenk, Karsten, additional, Nickenig, Georg, additional, Schuchlenz, Herwig, additional, Weikl, Stefan, additional, Lang, Irene Marthe, additional, Huber, Kurt, additional, Jakl‐Kotauschek, Gabriele, additional, Vertes, Andras, additional, Varga, Albert, additional, Fontos, Geza, additional, Merkely, Bela, additional, Kerecsen, Gabor, additional, Hinic, Sasa, additional, Zdravkovic, Marija, additional, Mudrenovic, Vladan, additional, Crnokrak, Bogdan, additional, Beleslin, Branko D., additional, Boskovic, Nikola N., additional, Petrovic, Marija T., additional, Dobric, Milan R., additional, Markovic, Zeljko Z., additional, Mladenovic, Ana S., additional, Cemerlic‐Adjic, Nada, additional, Davidovic, Goran, additional, Vucic, Rada, additional, Dekleva, Milica Nikola, additional, Stankovic, Goran, additional, Apostolovic, Svetlana, additional, Escobedo, Jorge, additional, Baleón‐Espinosa, Rubén, additional, Campos‐Santaolalla, Arturo S., additional, Durán‐Cortés, Elihú, additional, Flores‐Palacios, José M., additional, García‐Rincón, Andrés, additional, Jiménez‐Santos, Moisés, additional, Peñafiel, Joaquín V., additional, Ortega‐Ramírez, José A., additional, Valdespino‐Estrada, Aquiles, additional, Rosas, Erick Alexánderson, additional, Selvanayagam, Joseph B., additional, Joseph, Majo X., additional, Thambar, Suku T., additional, Beltrame, John F., additional, Hillis, Graham S., additional, Thuaire, Christophe, additional, Dutoiu, Téodora, additional, Steg, Philippe Gabriel, additional, Juliard, Jean‐Michel, additional, Slama, Michel S., additional, El Mahmoud, Rami, additional, Nicollet, Eric, additional, Goube, Pascal, additional, Barone‐Rochette, Gilles, additional, Furber, Alain, additional, Bière, Loïc, additional, Laucevicius, Aleksandras, additional, Celutkiene, Jelena, additional, Kedhi, Elvin, additional, Timmer, Jorik, additional, Hermanides, Rik, additional, Kaplan, Eliza, additional, Riezebos, Robert K., additional, Samadi, Pouneh, additional, van Dongen, Elise, additional, Niehe, Sander R., additional, Suryapranata, Harry, additional, van Vugt, Stijn, additional, Ramos, Ruben, additional, Cacela, Duarte, additional, Santana, Ana, additional, Fiarresga, Antonio, additional, Sousa, Lidia, additional, Marques, Hugo, additional, Patricio, Lino, additional, Bernanrdes, Luis, additional, Rio, Pedro, additional, Carvalho, Ramiro, additional, Ferreira, Rui, additional, Silva, Tiago, additional, Rodrigues, Ines, additional, Modas, Pedro, additional, Portugal, Guilherme, additional, Fragata, Jose, additional, Pinto, Fausto J., additional, Menezes, Miguel Nobre, additional, Lopes, Guilhermina Cantinho, additional, Almeida, Ana Gomes, additional, Silva, Pedro Canas, additional, Nobre, Angelo, additional, Francisco, Ana Rita, additional, Ferreira, Nuno, additional, Lopes, Ricardo L., additional, Guzman, Luis, additional, Figal, Julio César, additional, Méndiz, Oscar, additional, Cortés, Claudia, additional, Favaloro, Roberto René, additional, Alvarez, Carlos, additional, Courtis, Javier, additional, Zeballos, Gabriela, additional, Schiavi, Lilia, additional, Rubio, Mariano, additional, Devlin, Gerard Patrick, additional, Fisher, Raewyn, additional, Stewart, Ralph Alan Huston, additional, White, Harvey Douglas, additional, Benatar, Jocelyne, additional, Kedev, Sasko, additional, Mitevska, Irena Peovska, additional, Kostovska, Elizabeta Srbinovska, additional, Pejkov, Hristo, additional, Eggers, Kai, additional, Frostfelt, Gunnar, additional, Johnston, Nina, additional, Olsowka, Maciej, additional, Åkerblom, Axel, additional, Soveri, Inga, additional, Aspberg, Johannes, additional, Sharir, Tali, additional, Elian, Dan, additional, Kerner, Arthur, additional, Massalha, Samia, additional, Fukuda, Keiichi, additional, Kohsaka, Shun, additional, Yasuda, Satoshi, additional, Nishimura, Shigeyuki, additional, Van de Werf, Frans, additional, Claes, Kathleen, additional, Hung, Chung‐Lieh, additional, Yun, Chun‐Ho, additional, Hou, Charles Jia‐Yin, additional, Kuo, Jen‐Yuan, additional, Yeh, Hung‐I, additional, Hung, Ta‐Chuan, additional, Li, Jiun‐Yi, additional, Chien, Chen‐Yen, additional, Tsai, Cheng‐Ting, additional, Liu, Chun‐Chieh, additional, Yu, Fa‐Chang, additional, Lin, Yueh‐Hung, additional, Lan, Wei‐Ren, additional, Yen, Chih‐Hsuan, additional, Tsai, Jui‐Peng, additional, Sung, Kuo‐Tzu, additional, Ntsekhe, Mpiko, additional, Pandie, Shaheen, additional, Viljoen, Charle A., additional, De Andrade, Marianne, additional, Moccetti, Tiziano, additional, Rossi, M. Grazia, additional, Abdelhamid, Magdy, additional, Adel, Ahmed, additional, Kamal, Ahmed, additional, Mahrous, Hossam, additional, El Kaffas, Sameh, additional, El Fishawy, Hussien, additional, Pop, Calin, additional, Claudia, Matei, additional, Popescu, Bogdan A., additional, Ginghina, Carmen, additional, Deleanu, Dan, additional, Iliescu, Vlad A., additional, Al‐Mallah, Mouaz H., additional, Aljzeeri, Ahmed, additional, Najm, Hani, additional, Alghamdi, Ali, additional, Ramos, Walter Enrique Mogrovejo, additional, Kuanprasert, Srun, additional, Prommintikul, Arintaya, additional, Nawarawong, Weerachai, additional, Woragidpoonpol, Surin, additional, Tepsuwan, Thitipong, additional, Taksaudom, Noppon, additional, Rimsukcharoenchai, Chataroon, additional, Euathrongchit, Juntima, additional, Wannasopha, Yutthaphan, additional, Yamwong, Sukit, additional, Sritara, Piyamitr, additional, Aramcharoen, Suthara, additional, Meemuk, Krissada, additional, Khairuddin, Ahmad, additional, Hadi, Hafidz Abd, additional, and Yahaya, Shaiful Azmi, additional

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2024
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