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Article ; Online: The effect of frequency (64-498 MHz) on specific absorption rate adjacent to metallic orthopedic screws in MRI: A numerical simulation study.

Jacobs, Paul / Fagan, Andrew J

2023 Volume 51, Issue 2, Page(s) 1074–1082

Abstract: Background: The imaging of patients with implanted electrically-conductive devices via magnetic resonance imaging at ultra-high fields is hampered by uncertainties relating to the potential for inducing tissue heating adjacent to the implant due to ... ...

Abstract	Background: The imaging of patients with implanted electrically-conductive devices via magnetic resonance imaging at ultra-high fields is hampered by uncertainties relating to the potential for inducing tissue heating adjacent to the implant due to coupling of energy from the incident electromagnetic field into the implant. Existing data in the peer-reviewed literature of comparisons across field strengths of tissue heating and its surrogate, the specific absorption rate (SAR), is scarce and contradictory, leading to further doubts pertaining to the safety of imaging patients with such devices. Purpose: The radiofrequency-induced SAR adjacent to orthopedic screws of varying length and at frequencies of 64 to 498 MHz was investigated via full-wave electromagnetic simulations, to provide an accurate comparison of SAR across MRI field strengths. Methods: Dipole antennas were used for RF transmission to achieve a uniform electric field tangential to the screws located 120 mm above the antenna midpoints, embedded in a bone-mimicking material. The input power to the antennas was constrained to achieve the following targets without the screw present: (i) E = 100 V/m, (ii) B Results: The peak SAR, occurring at the resonant screw length, substantially increased as the frequency decreased when the input power to the dipole antenna was constrained to achieve constant electric field in background tissue at the screws' locations. A similar pattern was observed when constraining input power to achieve constant B Conclusions: The study design allowed for a direct comparison to be performed of SAR across frequencies and implant lengths without the confounding effect of variable incident electric field. Lower frequencies produced substantially larger SAR values for implants approaching the resonant length for the worst-case uniform incident electric field along the screws' length. The data may inform risk-benefit assessments for imaging patients with orthopedic implants at the new clinical field strength of 7 Tesla.
MeSH term(s)	Humans ; Computer Simulation ; Electromagnetic Fields ; Radio Waves ; Prostheses and Implants ; Magnetic Resonance Imaging ; Phantoms, Imaging
Language	English
Publishing date	2023-12-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	188780-4
ISSN	2473-4209 ; 0094-2405
ISSN (online)	2473-4209
ISSN	0094-2405
DOI	10.1002/mp.16902
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Article ; Online: The Politics of Identity in the UK

Fagan, Andrew

Before, During and After Covid-19

2020

Keywords	covid19
Language	English
Publishing date	2020-07-01
Publisher	University of Essex
Publishing country	uk
Document type	Article ; Online
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Article ; Online: Surgical management of calcific valvular and coronary disease in a patient with alkaptonuria: a case report.

Boyd, Riley M / Bharadwaj, Sandeep N / Fagan, Andrew / Mehta, Christopher K

European heart journal. Case reports

2024 Volume 8, Issue 2, Page(s) ytae076

Abstract: Background: Alkaptonuria is a rare metabolic disease that causes an increase in homogentisic acid (HGA) due to a lack of enzymatic activity. Commonly, accumulation of HGA presents with dark discoloration of skin and other tissues, also known as ... ...

Abstract	Background: Alkaptonuria is a rare metabolic disease that causes an increase in homogentisic acid (HGA) due to a lack of enzymatic activity. Commonly, accumulation of HGA presents with dark discoloration of skin and other tissues, also known as ochronosis. Additionally, alkaptonuria can result in other clinical manifestations, including arthritis and cardiac disease. This case highlights alkaptonuria-related cardiac disease and challenges that cardiac surgery teams may face when treating this patient population. Case summary: A 62-year-old male with a history of alkaptonuria, Hodgkin's lymphoma treated with chemoradiation, hypertension, and hyperlipidaemia originally presented with shortness of breath in the setting of known cardiac disease. Cardiac work-up demonstrated aortic stenosis, mitral stenosis, and multivessel coronary artery disease requiring aortic valve replacement, mitral valve replacement, and coronary artery bypass grafting. During the operation, significant discoloration of tissue was observed. This correlated with areas of severe calcification, which was noted throughout both valves. Extensive debridement was required prior to proceeding to valve replacements. Additionally, near-infrared spectroscopy failed to provide accurate measurements of cerebral oxygenation. Discussion: Alkaptonuria is correlated with cardiovascular disease, particularly valvular disease. Intraoperatively, these patients may exhibit noticeable discoloration and severe calcification of various tissues. Additionally, traditional infrared-based methods of cerebral oxygenation monitoring may not be reliable; however, other options of cerebral monitoring may be feasible. With proper pre-operative planning, however, patients with alkaptonuria may safely undergo cardiac surgery.
Language	English
Publishing date	2024-02-16
Publishing country	England
Document type	Case Reports
ISSN	2514-2119
ISSN (online)	2514-2119
DOI	10.1093/ehjcr/ytae076
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Article: Carbon Nanomaterials (CNMs) in Cancer Therapy: A Database of CNM-Based Nanocarrier Systems.

Mohan, Hugh / Fagan, Andrew / Giordani, Silvia

Pharmaceutics

2023 Volume 15, Issue 5

Abstract: Carbon nanomaterials (CNMs) are an incredibly versatile class of materials that can be used as scaffolds to construct anticancer nanocarrier systems. The ease of chemical functionalisation, biocompatibility, and intrinsic therapeutic capabilities of many ...

Abstract	Carbon nanomaterials (CNMs) are an incredibly versatile class of materials that can be used as scaffolds to construct anticancer nanocarrier systems. The ease of chemical functionalisation, biocompatibility, and intrinsic therapeutic capabilities of many of these nanoparticles can be leveraged to design effective anticancer systems. This article is the first comprehensive review of CNM-based nanocarrier systems that incorporate approved chemotherapy drugs, and many different types of CNMs and chemotherapy agents are discussed. Almost 200 examples of these nanocarrier systems have been analysed and compiled into a database. The entries are organised by anticancer drug type, and the composition, drug loading/release metrics, and experimental results from these systems have been compiled. Our analysis reveals graphene, and particularly graphene oxide (GO), as the most frequently employed CNM, with carbon nanotubes and carbon dots following in popularity. Moreover, the database encompasses various chemotherapeutic agents, with antimicrotubule agents being the most common payload due to their compatibility with CNM surfaces. The benefits of the identified systems are discussed, and the factors affecting their efficacy are detailed.
Language	English
Publishing date	2023-05-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15051545
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Article: Single nuclear RNA sequencing of terminal ileum in patients with cirrhosis demonstrates multi-faceted alterations in the intestinal barrier.

Jiang, Xixian / Xu, Ying / Fagan, Andrew / Patel, Bhaumik / Zhou, Huiping / Bajaj, Jasmohan S

Cell & bioscience

2024 Volume 14, Issue 1, Page(s) 25

Abstract: Patients with cirrhosis have intestinal barrier dysfunction but the role of the individual cell types in human small intestine is unclear. We performed single-nuclear RNA sequencing (snRNAseq) in the pinch biopsies of terminal ileum of four age-matched ... ...

Abstract	Patients with cirrhosis have intestinal barrier dysfunction but the role of the individual cell types in human small intestine is unclear. We performed single-nuclear RNA sequencing (snRNAseq) in the pinch biopsies of terminal ileum of four age-matched men [56 years, healthy control, compensated, early (ascites and lactulose use) and advanced decompensated cirrhosis (ascites and rifaximin use)]. Cell type proportions, differential gene expressions, cell-type specific pathway analysis using IPA, and cellular crosstalk dynamics were compared. Stem cells, enterocytes and Paneth cells were lowest in advanced decompensation. Immune cells like naive CD4 + T cells were lowest while ITGAE + cells were highest in advanced decompensation patients. MECOM had lowest expression in stem cells in advanced decompensation. Defensin and mucin sulfation gene (PAPSS2) which can stabilize the mucus barrier expression were lowest while IL1, IL6 and TNF-related genes were significantly upregulated in the enterocytes, goblet, and Paneth cells in decompensated subjects. IPA analysis showed higher inflammatory pathways in enterocytes, stem, goblet, and Paneth cells in decompensated patients. Cellular crosstalk analysis showed that desmosome, protease-activated receptors, and cadherin-catenin complex interactions were most perturbed in decompensated patients. In summary, the snRNAseq of the human terminal ileum in 4 subjects (1 control and three cirrhosis) identified multidimensional alteration in the intestinal barrier with lower stem cells and altered gene expression focused on inflammation, mucin sulfation and cell-cell interactions with cirrhosis decompensation.
Language	English
Publishing date	2024-02-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2593367-X
ISSN	2045-3701
ISSN	2045-3701
DOI	10.1186/s13578-024-01209-5
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Article ; Online: Proton Pump Inhibitor Use and Complications of Cirrhosis Are Linked With Distinct Gut Microbial Bacteriophage and Eukaryotic Viral-Like Particle Signatures in Cirrhosis.

Peña Rodríguez, Marcela / Fagan, Andrew / Sikaroodi, Masoumeh / Gillevet, Patrick M / Bajaj, Jasmohan S

Clinical and translational gastroenterology

2024 Volume 15, Issue 2, Page(s) e00659

Abstract: Introduction: Proton pump inhibitors (PPIs) modulate the progression of cirrhosis to hepatic encephalopathy (HE) and can affect the bacterial microbiome. However, the impact of PPI on the virome in cirrhosis using viral-like particle (VLP) analysis is ... ...

Abstract	Introduction: Proton pump inhibitors (PPIs) modulate the progression of cirrhosis to hepatic encephalopathy (HE) and can affect the bacterial microbiome. However, the impact of PPI on the virome in cirrhosis using viral-like particle (VLP) analysis is unclear. Methods: We determined the VLP in the stool microbiome in patients with cirrhosis cross-sectionally (ascites, HE, and PPI use analyzed) who were followed up for 6-month hospitalizations and through 2 clinical trials of PPI withdrawal and initiation. Results: In a cross-sectional study, PPI users had greater ascites prevalence and 6-month hospitalizations, but VLP α diversity was similar. Among phages, PPI users had lower Autographviridae and higher Streptococcus phages and Herelleviridae than nonusers, whereas opposite trends were seen in ascites and HE. Trends of eukaryotic viruses (higher Adenoviridae and lower Virgaviridae/Smacoviridae) were similar for PPI, HE, and ascites. Twenty-one percent were hospitalized, mostly due to HE. α Diversity was similar in the hospitalized/nonhospitalized/not groups. Higher Gokushovirinae and lower crAssphages were related to hospitalizations such as HE-related cross-sectional VLP changes. As part of the clinical trial, PPIs were added and withdrawn in 2 different decompensated groups over 14 days. No changes in α diversity were observed. Withdrawal reduced crAssphages, and initiation reduced Gokushovirinae and Bacteroides phages. Discussion: In cirrhosis, PPI use has a gut microbial VLP phage signature that is different from that in HE and ascites, and VLP changes are linked with hospitalizations over 6 months, independent of clinical biomarkers. Eukaryotic viral patterns were consistent across PPI use, HE, and ascites, indicating a relationship with the progression of cirrhosis. PPIs alone showed modest VLP changes with withdrawal or initiation. Distinct phage and eukaryotic viral patterns are associated with the use of PPIs in cirrhosis.
MeSH term(s)	Humans ; Ascites/complications ; Bacteriophages ; Cross-Sectional Studies ; Gastrointestinal Microbiome ; Hepatic Encephalopathy/complications ; Liver Cirrhosis/complications ; Proton Pump Inhibitors/therapeutic use ; Proton Pump Inhibitors/pharmacology ; Clinical Trials as Topic
Chemical Substances	Proton Pump Inhibitors
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2581516-7
ISSN	2155-384X ; 2155-384X
ISSN (online)	2155-384X
ISSN	2155-384X
DOI	10.14309/ctg.0000000000000659
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Article ; Online: Minimizing magnetic resonance image geometric distortion at 7 Tesla for frameless presurgical planning using skin-adhered fiducials.

Kirby, Krystal M / Koons, Emily K / Welker, Kirk M / Fagan, Andrew J

Medical physics

2022 Volume 50, Issue 2, Page(s) 694–701

Abstract: Background: 7T MRI offers significant benefits to spatial and contrast resolution compared to lower field strengths. This superior image quality can help better delineate targets in stereotactic neurosurgical procedures; however, the potential for ... ...

Abstract	Background: 7T MRI offers significant benefits to spatial and contrast resolution compared to lower field strengths. This superior image quality can help better delineate targets in stereotactic neurosurgical procedures; however, the potential for increased geometric distortions at 7T has impaired its widespread use for these applications. Image geometric distortions can be due to distortions of B Purpose: The purpose of this study was to investigate the use of 7T MRI for neurosurgical frameless stereotactic navigation procedures. Image geometric distortions at the skin surface in 7T images were minimized and compared to results from clinical 3T frameless imaging protocols. Methods: A 3D-printed grid phantom filled with oil was designed to perform a fine calibration of the 7T imaging gradients, and an oil-filled head phantom with internal targets was used to determine ground truth (from computed tomography [CT]) positioning errors. Three volunteers and the head phantom were imaged consecutively at 3T and 7T. Ten skin-adhesive fiducial markers were placed on each subject's exposed skin surface at standard clinical placement locations for frameless procedures. Imaging sequences included MPRAGE (three bandwidths at 7T: 400, 690, and 1020 Hz/pixel, and one at 3T: 400 Hz/pixel), T2 SPACE, and T2 SPACE FLAIR acquisitions. An additional GRE field map was acquired on both scanners using a multi-echo GRE sequence. Custom Matlab code was used to perform additional distortion correction of the images using the unwrapped field maps. Fiducial localization was performed with 3D Slicer, with absolute fiducial positioning errors determined in phantom experiments following rigid registration to the CT images. For human experiments, 3T and 7T images were registered and relative differences in fiducial locations were compared using two-tailed paired t-tests. Results: Phantom measurements at 7T yielded gradient distance scaling errors of 1.1%, 2.2%, and 1.0% along the x-, y-, and z-axes, respectively. These system miscalibrations were traced back to phantom manufacturing deviations in the sphericity of the vendor's gradient calibration phantom. Correction factors along each gradient axis were applied, and afterward, geometric distortions of less than 1 mm were obtained in the 7T MR head phantom images for the 1020 Hz/pixel bandwidth MPRAGE sequence. For the human subjects, four fiducial locations were excluded from the analysis due to patient positioning differences. Differences between 3T and 7T MPRAGE with low/medium/high bandwidth were 2.2 /2.6/2.3 mm, respectively, before the correction, reducing to 1.6/1.3/1.0 mm after the correction (p < 0.001). T2 SPACE and T2 SPACE FLAIR yielded a similar pattern when the correction was applied, decreasing from 2.1 to 0.8 mm, and 2.6 to 1.0 mm, respectively. Conclusions: 7T MRI can be used to perform frameless presurgical planning with skin-adhesive fiducials. Geometric distortions can be reduced to a clinically relevant level (errors < ∼1 mm) with no significant susceptibility-related distortions, by using high receiver bandwidth, ensuring gradients are properly calibrated, and placing skin fiducials in areas where distortions from patient positioning are minimal.
MeSH term(s)	Humans ; Imaging, Three-Dimensional/methods ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging/methods ; Phantoms, Imaging
Language	English
Publishing date	2022-11-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	188780-4
ISSN	2473-4209 ; 0094-2405
ISSN (online)	2473-4209
ISSN	0094-2405
DOI	10.1002/mp.16035
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Article: Development and Evaluation of a Multifrequency Ultrafast Doppler Spectral Analysis (MFUDSA) Algorithm for Wall Shear Stress Measurement: A Simulation and In Vitro Study.

Malone, Andrew J / Cournane, Seán / Naydenova, Izabela / Meaney, James F / Fagan, Andrew J / Browne, Jacinta E

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 11

Abstract: Cardiovascular pathology is the leading cause of death and disability in the Western world, and current diagnostic testing usually evaluates the anatomy of the vessel to determine if the vessel contains blockages and plaques. However, there is a growing ... ...

Abstract	Cardiovascular pathology is the leading cause of death and disability in the Western world, and current diagnostic testing usually evaluates the anatomy of the vessel to determine if the vessel contains blockages and plaques. However, there is a growing school of thought that other measures, such as wall shear stress, provide more useful information for earlier diagnosis and prediction of atherosclerotic related disease compared to pulsed-wave Doppler ultrasound, magnetic resonance angiography, or computed tomography angiography. A novel algorithm for quantifying wall shear stress (WSS) in atherosclerotic plaque using diagnostic ultrasound imaging, called Multifrequency ultrafast Doppler spectral analysis (MFUDSA), is presented. The development of this algorithm is presented, in addition to its optimisation using simulation studies and in-vitro experiments with flow phantoms approximating the early stages of cardiovascular disease. The presented algorithm is compared with commonly used WSS assessment methods, such as standard PW Doppler, Ultrafast Doppler, and Parabolic Doppler, as well as plane-wave Doppler. Compared to an equivalent processing architecture with one-dimensional Fourier analysis, the MFUDSA algorithm provided an increase in signal-to-noise ratio (SNR) by a factor of 4-8 and an increase in velocity resolution by a factor of 1.10-1.35. The results indicated that MFUDSA outperformed the others, with significant differences detected between the typical WSS values of moderate disease progression (
Language	English
Publishing date	2023-05-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13111872
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Article: Spiropyran-Based Drug Delivery Systems.

Fagan, Andrew / Bartkowski, Michał / Giordani, Silvia

Frontiers in chemistry

2021 Volume 9, Page(s) 720087

Abstract: Nanocarriers are rapidly growing in popularity in the field of drug delivery. The ability of nanocarriers to encapsulate and distribute poorly soluble drugs while minimising their undesired effects is significantly advantageous over traditional drug ... ...

Abstract	Nanocarriers are rapidly growing in popularity in the field of drug delivery. The ability of nanocarriers to encapsulate and distribute poorly soluble drugs while minimising their undesired effects is significantly advantageous over traditional drug delivery. Nanocarriers can also be decorated with imaging moieties and targeting agents, further incrementing their functionality. Of recent interest as potential nanocarriers are spiropyrans; a family of photochromic molecular switches. Due to their multi-responsiveness to endo- and exogenous stimuli, and their intrinsic biocompatibility, they have been utilised in various drug delivery systems (DDSs) to date. In this review, we provide an overview of the developments in spiropyran-based DDSs. The benefits and drawbacks of utilising spiropyrans in drug delivery are assessed and an outline of spiropyran-based drug delivery systems is presented.
Language	English
Publishing date	2021-07-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2711776-5
ISSN	2296-2646
ISSN	2296-2646
DOI	10.3389/fchem.2021.720087
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Article ; Online: A specialized HE testing clinic improves rational decision-making for therapy in cirrhosis.

Nadeem, Mahum / Tafader, Asiya / Park, Dan / Fagan, Andrew / Wade, James B / Bajaj, Jasmohan S

Hepatology communications

2023 Volume 7, Issue 11

Abstract: Background: Cognitive complaints in cirrhosis are often attributed to HE with reflexive therapy if specialized tests are not performed. The aim was to determine the utility of a specialized HE clinic for management decisions.: Methods: Cirrhosis ... ...

Abstract	Background: Cognitive complaints in cirrhosis are often attributed to HE with reflexive therapy if specialized tests are not performed. The aim was to determine the utility of a specialized HE clinic for management decisions. Methods: Cirrhosis patients with cognitive complaints were referred through a dedicated consult pathway to a specialized clinic and followed for 6 months. This clinic included detailed history, medication review, standardized tests [Mini-Mental Status Exam (MMSE), Psychometric HE Score, and others], and obstructive sleep apnea screening. Results were communicated with patients and referring providers. A subset was offered repeat testing. Results: A total of 286 patients were tested between 2012 and 2022. Of the 286 patients, 4 patients who showed a Mini-Mental State Exam <25 were referred to neurology. Thirty-nine percent had normal Psychometric HE Score (higher in younger patients, without prior HE, depression, and lower Model for End-Stage Liver Disease-Sodium), while 172 (61%) patients had cognitive impairment. Of the 172 patients, 51 did not want management change, 84 were started on HE therapy, and 37 were considered impaired due to other causes. In 51 without management change, 32 refused lactulose, while the remaining were counseled regarding lactulose titration. Of the 84 patients with HE-therapy initiation, lactulose was initiated in 56 and rifaximin in 28; most therapies continued over 6 months. The ones who were retested improved their Psychometric HE Score. The 37 with other causes (obstructive sleep apnea, mood disorders, substance use, and mild cognitive impairment) led to specialized referrals. No overt HE was found over 6 months in those without HE-related impairment. The clinic was billed for. Conclusions: A specialized HE clinic for patients with cirrhosis and cognitive complaints established through a dedicated consult pathway showed that 39% of referred patients had normal cognitive performance, while the results guided management changes, including for HE and other causes in the remaining patients.
MeSH term(s)	Humans ; Lactulose/therapeutic use ; Gastrointestinal Agents/therapeutic use ; Hepatic Encephalopathy/diagnosis ; Hepatic Encephalopathy/drug therapy ; End Stage Liver Disease ; Severity of Illness Index ; Liver Cirrhosis/complications ; Liver Cirrhosis/diagnosis ; Liver Cirrhosis/drug therapy ; Sleep Apnea, Obstructive/diagnosis ; Sleep Apnea, Obstructive/therapy ; Sleep Apnea, Obstructive/complications
Chemical Substances	Lactulose (4618-18-2) ; Gastrointestinal Agents
Language	English
Publishing date	2023-10-12
Publishing country	United States
Document type	Journal Article
ISSN	2471-254X
ISSN (online)	2471-254X
DOI	10.1097/HC9.0000000000000301
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