70 results on '"B. Doyle"'
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2. The CASEL Framework and Christian Schools: Using a Hermeneutical Tool to Determine Worldview Alignment
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Jill L. Swisher and Lori B. Doyle
- Abstract
This article aims to utilize an adapted version of Trentham's Inverse Consistency Protocol (ICP) as a way in which any ecclesial organization can act productively when confronted with seemingly controversial paradigms such as social emotional learning (SEL). The ICP can help Christian leaders discern potential areas of inconsistency or affirm authentic congruence with an organization's faith tradition. Tenets from the Collaborative for Academic, Social, and Emotional Learning (CASEL) were submitted through the four-step protocol. Findings suggest that CASEL is a valuable framework when applied authentically and that ICP is a constructive tool for engaging in the social sciences with integrity.
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- 2024
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3. Coaching and Coursework Focused on Teacher-Child Interactions during Language/Literacy Instruction: Effects on Teacher Outcomes and Children's Classroom Engagement
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Jason T. Downer, Nicole B. Doyle, Robert C. Pianta, Margaret Burchinal, Samuel Field, Bridget K. Hamre, Jennifer LoCasale-Crouch, Carollee Howes, Karen LaParo, and Catherine Scott-Little
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A sample of 496 early childhood teachers was assigned randomly in two phases to a series of professional development (PD) interventions. Phase I intervention was a 14-week course on effective teacher-child interactions. Participants were then re-randomized into Phase II intervention, which consisted of individual, interactions-focused coaching. Impacts of the course, coaching, and their combination were evaluated relative to business-as-usual controls on knowledge of effective interactions, skill in detecting effective interactions, observed teacher-child interactions, beliefs about intentional teaching, and children's classroom engagement. "Research Findings:" Teachers exposed to the course demonstrated greater knowledge of and skills in detecting effective teacher child-interactions, and displayed higher quality instructional support in their interactions with children during the year following the course. Teachers who received coaching were also observed to display higher levels of instructional support and children in their classrooms displayed more positive engagement with adults. However, neither teachers nor children appeared to gain additional benefit from the combination of the course and coaching. "Practice or Policy:" The results have important implications for efforts to systematically and efficiently improve the quality of early childhood programs through the delivery of PD that is directly aligned with teachers' classroom interactions.
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- 2024
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4. Understanding Teachers' Emotion Regulation Strategies and Related Teacher and Classroom Factors
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Nicole B. Doyle, Jason T. Downer, and Sara E. Rimm-Kaufman
- Abstract
Today's teachers face intense stress (Robinson et al. in School Mental Health 15(1):78-89, 2023), which means they often need to regulate strong emotions, like frustration and anxiety, in the classroom. Given the importance of this skill for classroom life, it is essential that we gain a more nuanced understanding of teachers' emotion regulation (ER). The teacher ER literature is growing, and we aim to contribute meaningfully in three ways. First, we examine two general ER strategies (cognitive reappraisal and expressive suppression) descriptively in a sample of 190 public school teachers (grades K-6) from 33 elementary schools. Second, we explore whether these two ER strategies are correlated with important teacher (burnout, years of experience) and classroom (class size) factors. Third, we examine whether these ER strategies are linked to observed emotionally supportive classroom interactions. Teachers in this sample reported frequent use of cognitive reappraisal and relatively infrequent use of expressive suppression in general. These two ER strategies were not significantly correlated with one another. Teachers reporting greater use of cognitive reappraisal reported less burnout, while teachers reporting greater use of expressive suppression reported more burnout. Teachers with more years of experience also reported greater use of cognitive reappraisal. Contrary to our hypotheses, cognitive reappraisal and expressive suppression were not related to class size and did not predict unique variance in observed emotionally supportive interactions. Implications for teacher supports and interventions are discussed.
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- 2024
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5. Nearshore wave buoy data from southeastern Australia for coastal research and management
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Michael A. Kinsela, Bradley D. Morris, Timothy C. Ingleton, Thomas B. Doyle, Michael D. Sutherland, Neil E. Doszpot, Jeff J. Miller, Stephen F. Holtznagel, Mitchell D. Harley, and David J. Hanslow
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Science - Abstract
Abstract Wind wave observations in shallow coastal waters are essential for calibrating, validating, and improving numerical wave models to predict sediment transport, shoreline change, and coastal hazards such as beach erosion and oceanic inundation. Although ocean buoys and satellites provide near-global coverage of deep-water wave conditions, shallow-water wave observations remain sparse and often inaccessible. Nearshore wave conditions may vary considerably alongshore due to coastline orientation and shape, bathymetry and islands. We present a growing dataset of in-situ wave buoy observations from shallow waters (
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- 2024
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6. Using Teacher Presence in Online Higher Education to Foster Global Citizenship among Adult Learners
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Tanya M. Tarbutton and Lori B. Doyle
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global citizenship ,online education ,adult learners ,higher education ,community of inquiry ,teacher presence ,Education - Abstract
Higher education institutions must recognize the responsibility to support online adult learners as members of a larger global community and technological advancements have made this a reality. COVID-19 restrictions to in-person learning highlighted the need for online learning platforms that promote the benefits of teacher presence, consider the tenets of the Community of Inquiry model, and commit to the principles of andragogy. A need to explore the possibilities for fostering global citizenship among adult learners in online higher education environments has been identified as a problem space and a methodological approach will be used to connect findings from the literature with best practices for practitioners. Global citizenship is not a new concept; however, current and worldwide events have created a renewed dedication to the construct. Discussions based on the literature and established theoretical frameworks will precede practical implications for directors, course designers, and instructors. Online education will be described as ripe with opportunities for higher education institutions to foster global citizenship among adult learners.
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- 2023
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7. Foredune erosion, overtopping and destruction in 2022 at Bengello Beach, southeastern Australia
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Thomas S. N. Oliver, Michael A. Kinsela, Thomas B. Doyle, and Roger F. McLean
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coastal storm ,backshore erosion ,storm impacts ,beach erosion ,foredune erosion ,Harbors and coast protective works. Coastal engineering. Lighthouses ,TC203-380 ,Oceanography ,GC1-1581 - Abstract
The beach–foredune system at Bengello Beach has been monitored monthly to bimonthly at four profiles (P1–P4) since 1972 and documented the building of a foredune. This paper addresses the remarkable changes which occurred in 2022 as storm waves overtopped and trimmed this foredune at all profiles, then later removed this entire feature at two of the profiles (P3, P4) but not the others (P1, P2). Wave parameters for these storm events, measured by deepwater and nearshore wave buoys, enable a comparison of storm characteristics and resulting beach–foredune impact. During the storm event which destroyed the foredune, nearshore wave height exceeded deepwater wave height, in contrast with other storms that year. The beach–foredune lost 78 m3/m in 2022 and the notable 1974 storms that impacted this coastline resulted in 95 m3/m volume loss. During 2023, beach recovery has occurred, but not rebuilt the foredune. It had persisted for ~40 years enduring many other severe storm events, and the coastal protection afforded by the dune system has been compromised. This highlights the need to consider dune morphology in assessments of erosion hazard and inundation risk along similar coastlines.
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- 2024
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8. Vaborbactam increases meropenem susceptibility in Pseudomonas aeruginosa clinical isolates displaying MexXY and AmpC upregulation
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Mariana Castanheira, Timothy B. Doyle, Cory M. Hubler, Sean DeVries, and Dee Shortridge
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P. aeruginosa ,β-lactam/β-lactamase inhibitor combinations ,efflux ,Microbiology ,QR1-502 - Abstract
ABSTRACT To evaluate the resistance mechanisms among Pseudomonas aeruginosa clinical isolates exhibiting meropenem (MEM) MIC values higher than meropenem-vaborbactam (MEV). P. aeruginosa clinical isolates collected in US hospitals from 2014 to 2019 were susceptibility tested. Whole-genome and transcriptome sequencing were performed. Results were analyzed for strain typing, acquired β-lactamases, and mutations in chromosomal genes; gene expression was measured for known β-lactam resistance contributors. Results were compared to a control group of 10 P. aeruginosa isolates displaying MIC values at 8 mg/L for meropenem ± vaborbactam (MEM = MEV). Out of 88 isolates displaying MEM > MEV, 33 (37.5%) isolates had reproducibly lower MIC values for meropenem-vaborbactam compared to meropenem when retested. The expression of mexX, mexY, mexZ, and ampC was significantly greater among a higher percentage of the MEM > MEV isolates. Furthermore, the association of mexXY and ampC overexpression was detected in 17/33 MEM > MEV isolates and only 1/10 MEM = MEV isolate. In addition, the Pseudomonas-derived cephalosporinase amino acid substitution R79Q was detected among 33.3% of the isolates displaying MEM > MEV, and none of the isolates displayed MEM = MEV. Other resistance mechanisms were not observed or were equally observed in both groups. In rare cases, vaborbactam plays a role in lowering the meropenem MIC values in P. aeruginosa clinical isolates likely due to the inhibition of the AmpC gene that was overexpressed in the presence of upregulation of MexXY with or without alterations in the AmpC gene. IMPORTANCE Pseudomonas aeruginosa isolates are intrinsically resistant to multiple antimicrobial agents and meropenem is an important therapeutic option to treat infections caused by this organism. Meropenem-vaborbactam activity is similar to that of meropenem alone against P. aeruginosa isolates. Isolates belonging to this species that display lower meropenem-vaborbactam compared to meropenem are rare. We initiated this study to understand the resistance mechanisms that could lead to lower meropenem-vaborbactam MIC values when compared to meropenem alone. We documented that isolates displaying lower meropenem-vaborbactam exhibited overexpression of MexXY and AmpC. In addition, isolates displaying the R79Q PDC (AmpC) mutation were more likely to display lower meropenem-vaborbactam when compared to isolates displaying the same MIC values for these agents.
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- 2023
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9. Closing the Gap in Prophylactic Treatment of Duodenal Endoscopic Submucosal Dissection Defects
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John B. Doyle and Kavel Visrodia
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2023
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10. Identification and Characterization of ML321: A Novel and Highly Selective D2 Dopamine Receptor Antagonist with Efficacy in Animal Models That Predict Atypical Antipsychotic Activity
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R. Benjamin Free, Ashley N. Nilson, Noelia M. Boldizsar, Trevor B. Doyle, Ramona M. Rodriguiz, Vladimir M. Pogorelov, Mayako Machino, Kuo Hao Lee, Jeremiah W. Bertz, Jinbin Xu, Herman D. Lim, Andrés E. Dulcey, Robert H. Mach, James H. Woods, J Robert Lane, Lei Shi, Juan J. Marugan, William C. Wetsel, and David R. Sibley
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Pharmacology ,Pharmacology (medical) - Published
- 2022
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11. The plethora of resistance mechanisms in Pseudomonas aeruginosa: transcriptome analysis reveals a potential role of lipopolysaccharide pathway proteins to novel β-lactam/β-lactamase inhibitor combinations
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Mariana Castanheira, Timothy B. Doyle, Cory M. Hubler, Timothy D. Collingsworth, Sean DeVries, and Rodrigo E. Mendes
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Lipopolysaccharides ,Microbiology (medical) ,Tazobactam ,Lactams ,Gene Expression Profiling ,Immunology ,Microbial Sensitivity Tests ,Microbiology ,beta-Lactamases ,Anti-Bacterial Agents ,Cephalosporins ,Pseudomonas aeruginosa ,Humans ,Immunology and Allergy ,Pseudomonas Infections ,beta-Lactamase Inhibitors ,Monobactams - Abstract
Whole genome and transcriptome analysis of 213 Pseudomonas aeruginosa isolates resistant to antipseudomonal β-lactams collected in 30 countries was performed to evaluate resistance mechanisms against these agents.Isolates were susceptibility tested by reference broth microdilution. Whole genome and transcriptome sequencing were performed, and data were analysed using open-source tools. A statistical analysis of changes in the expression of5500 genes was compared to the expression of PAO1.The high-risk clones ST235 and ST111 were the most prevalent among90 sequence types (STs). Metallo-β-lactamase (MBLs) genes were detected in 40 isolates. AmpC and MexXY were the most common genes overexpressed in approximately 50% of the 173 isolates that did not carry MBLs. Isolates overexpressing pmrA and pmrB, the norspermidine production genes speD2 and speE2, and the operon arnBCADTEF-ugd were noted among strains resistant to ceftolozane-tazobactam and ceftazidime-avibactam, despite the lack of polymyxin resistance often associated to increased expression of these genes. Overexpression of MuxABC-OpmB, OprG, and OprE proteins were associated with resistance to ceftolozane-tazobactam in addition to the usual genes involved in cephalosporin, monobactam, and carbapenem resistance. Statistical analysis identified discrete mutations in ArmZ, OprD, and AmpC that correlated to antipseudomonal β-lactam resistance.P. aeruginosa resistance mechanisms are complex. This analysis suggests the role of multiple genes in resistance to antipseudomonal β-lactams, including some not commonly described.
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- 2022
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12. Liver transplantation as a new standard of care in patients with perihilar cholangiocarcinoma?
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Eva Breuer, Matteo Mueller, Majella B. Doyle, Liu Yang, Sarwa Darwish Murad, Imran J. Anwar, Shaheed Merani, Ashley Limkemann, Heithem Jeddou, Steven C. Kim, Victor López-López, Ahmed Nassar, Frederik J.H. Hoogwater, Eric Vibert, Michelle L. De Oliveira, Daniel Cherqui, Robert J. Porte, Joseph F. Magliocca, Lutz Fischer, Constantino Fondevila, Krzysztof Zieniewicz, Pablo Ramírez, David P. Foley, Karim Boudjema, Austin D. Schenk, Alan N. Langnas, Stuart Knechtle, Wojciech G. Polak, C. Burcin Taner, William C. Chapman, Charles B. Rosen, Gregory J. Gores, Philipp Dutkowski, Julie K. Heimbach, Pierre-Alain Clavien, Gastroenterology & Hepatology, Surgery, and Groningen Institute for Organ Transplantation (GIOT)
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Complications ,Liver transplantation ,CCI ,Benchmarks ,Standard of Care ,Outcomes ,Mayo-protocol ,Cholangiocarcinoma ,Benchmarking ,Bile Duct Neoplasms ,Humans ,Surgery ,Perihilar cholangiocarcinoma ,Klatskin Tumor - Abstract
Objective: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons.Background: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC.Methods: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014–2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥ 50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter Results: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤ 5.2%; comprehensive complication index at 1 year of ≤ 33.7; grade ≥ 3 complication rates ≤ 66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n = 106) (62% vs 32%, P < 0.001).Conclusion: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC.
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- 2022
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13. Body mass index and additional risk factors for cancer in adults with cystic fibrosis
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Rita M. Knotts, Zhezhen Jin, John B. Doyle, Claire Keating, Emily DiMango, and Julian A. Abrams
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Cancer Research ,Oncology - Published
- 2022
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14. Liver Transplantation After Hepatic Artery Infusion Pump Therapy: Single-Center Experience and Technical Considerations
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Angela L. Hill, Darren R. Cullinan, Ola Ahmed, Neeta Vachharajani, Meranda D. Scherer, Franklin Olumba, Adeel S. Khan, William C. Chapman, and Majella B. Doyle
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Oncology ,Surgery - Published
- 2023
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15. Engineered phage with antibacterial CRISPR–Cas selectively reduce E. coli burden in mice
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Yilmaz Emre Gencay, Džiuginta Jasinskytė, Camille Robert, Szabolcs Semsey, Virginia Martínez, Anders Østergaard Petersen, Katja Brunner, Ana de Santiago Torio, Alex Salazar, Iszabela Cristiana Turcu, Melissa Kviesgaard Eriksen, Lev Koval, Adam Takos, Ricardo Pascal, Thea Staffeldt Schou, Lone Bayer, Tina Bryde, Katja Chandelle Johansen, Emilie Glad Bak, Frenk Smrekar, Timothy B. Doyle, Michael J. Satlin, Aurelie Gram, Joana Carvalho, Lene Jessen, Björn Hallström, Jonas Hink, Birgitte Damholt, Alice Troy, Mette Grove, Jasper Clube, Christian Grøndahl, Jakob Krause Haaber, Eric van der Helm, Milan Zdravkovic, and Morten Otto Alexander Sommer
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Biomedical Engineering ,Molecular Medicine ,Bioengineering ,Applied Microbiology and Biotechnology ,Biotechnology - Abstract
Antibiotic treatments have detrimental effects on the microbiome and lead to antibiotic resistance. To develop a phage therapy against a diverse range of clinically relevant Escherichia coli, we screened a library of 162 wild-type (WT) phages, identifying eight phages with broad coverage of E. coli, complementary binding to bacterial surface receptors, and the capability to stably carry inserted cargo. Selected phages were engineered with tail fibers and CRISPR–Cas machinery to specifically target E. coli. We show that engineered phages target bacteria in biofilms, reduce the emergence of phage-tolerant E. coli and out-compete their ancestral WT phages in coculture experiments. A combination of the four most complementary bacteriophages, called SNIPR001, is well tolerated in both mouse models and minipigs and reduces E. coli load in the mouse gut better than its constituent components separately. SNIPR001 is in clinical development to selectively kill E. coli, which may cause fatal infections in hematological cancer patients.
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- 2023
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16. Understanding High Quality Teacher-Student Interactions in High Needs Elementary Schools: An Exploration of Teacher, Student, and Relational Contributors
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Nicole B. Doyle, Jason T. Downer, Joshua L. Brown, and Amy E. Lowenstein
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Developmental and Educational Psychology ,Education - Published
- 2022
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17. Using Teacher Presence in Online Higher Education to Foster Global Citizenship among Adult Learners
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Tanya M. Tarbutton and Lori B. Doyle
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Education - Abstract
Higher education institutions must recognize the responsibility to support online adult learners as members of a larger global community and technological advancements have made this a reality. COVID-19 restrictions to in-person learning highlighted the need for online learning platforms that promote the benefits of teacher presence, consider the tenets of the Community of Inquiry model, and commit to the principles of andragogy. A need to explore the possibilities for fostering global citizenship among adult learners in online higher education environments has been identified as a problem space and a methodological approach will be used to connect findings from the literature with best practices for practitioners. Global citizenship is not a new concept; however, current and worldwide events have created a renewed dedication to the construct. Discussions based on the literature and established theoretical frameworks will precede practical implications for directors, course designers, and instructors. Online education will be described as ripe with opportunities for higher education institutions to foster global citizenship among adult learners. Keywords: global citizenship, online education, adult learners, higher education, Community of Inquiry, teacher presence
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- 2022
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18. COVID Vaccination Status and Operative Outcomes after Kidney Transplantation
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Bradley S Kushner, Maria B Doyle, Adeel S Khan, Yiing Lin, Tarek Alhamad, Jennifer Yu, William C Chapman, and Jason R Wellen
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Surgery - Published
- 2023
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19. Virtual Ancillary Faculty
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Lori B. Doyle and Tanya M. Tarbutton
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Virtual ancillary faculty are instrumental in delivering online instruction and fostering student success across higher education institutions. Program directors should create models of support using performance outcomes and verbal persuasion to foster self-efficacy in order to help instructors avoid feelings of depersonalization that can lead to burnout. The job-demands resources model has been shown to support supervisor efforts to recognize work-related demands in order to provide purposeful resources. The authors of this chapter work as program directors and share examples, rationale, and expertise through a case study approach which highlights best practices for working with virtual ancillary faculty including an in-depth examination of teacher evaluation and professional development strategies.
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- 2023
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20. Modified Foredune Eco-Morphology in Southeast Australia
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Thomas B. Doyle and Colin D. Woodroffe
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Management, Monitoring, Policy and Law ,Aquatic Science ,Oceanography - Published
- 2023
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21. Correction to: Absence of ferromagnetic behaviour in Mn implanted ZnO
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K. Bharuth-Ram, T. B. Doyle, V. Adoons, and C. Ronning
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Nuclear and High Energy Physics ,Physical and Theoretical Chemistry ,Condensed Matter Physics ,Atomic and Molecular Physics, and Optics - Published
- 2022
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22. Absence of ferromagnetic behaviour in Mn implanted ZnO
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K. Bharuth-Ram, T. B. Doyle, V. Adoons, and C. Ronning
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Nuclear and High Energy Physics ,Physical and Theoretical Chemistry ,Condensed Matter Physics ,Atomic and Molecular Physics, and Optics - Published
- 2022
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23. Identification and Characterization of ML321: a Novel and Highly Selective D2Dopamine Receptor Antagonist with Efficacy in Animal Models that Predict Atypical Antipsychotic Activity
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R. Benjamin Free, Ashley N. Nilson, Noelia M. Boldizsar, Trevor B. Doyle, Ramona M. Rodriguiz, Vladimir M. Pogorelov, Mayako Machino, Kuo Hao Lee, Jeremiah W. Bertz, Jinbin Xu, Herman D. Lim, Andrés E. Dulcey, Robert H. Mach, James H. Woods, J Robert Lane, Lei Shi, Juan J. Marugan, William C. Wetsel, and David R. Sibley
- Abstract
We have developed and characterized a novel D2R antagonist with exceptional GPCR selectivity – ML321. In functional profiling screens of 168 different GPCRs, ML321 showed little activity beyond potent inhibition of the D2R, and to a lesser extent the D3R, demonstrating excellent receptor selectivity. The D2R selectivity of ML321 may be related to the fact that, unlike other monoaminergic ligands, ML321 lacks a positively charged amine group and adopts a unique binding pose within the orthosteric binding site of the D2R. PET imaging studies in non-human primates demonstrated that ML321 penetrates the CNS and occupies the D2R in a dose-dependent manner. Behavioral paradigms in rats demonstrate that ML321 can selectively antagonize a D2R-mediated response (hypothermia) while not affecting a D3R-mediated response (yawning) using the same dose of drug, thus indicating exceptionalin vivoselectivity. We also investigated the effects of ML321 in animal models that are predictive of antipsychotic efficacy in humans. We found that ML321 attenuates both amphetamine- and phencyclidine-induced locomotor activity and restored pre-pulse inhibition (PPI) of acoustic startle in a dose-dependent manner. Surprisingly, using doses that were maximally effective in both the locomotor and PPI studies, ML321 was relatively ineffective in promoting catalepsy. Kinetic studies revealed that ML321 exhibits slow-on and fast-off receptor binding rates, similar to those observed with atypical antipsychotics with reduced extrapyramidal side effects. Taken together, these observations suggest that ML321, or a derivative thereof, may exhibit “atypical” antipsychotic activity in humans with significantly fewer side effects than observed with currently FDA-approved D2R antagonists.
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- 2022
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24. 2 Pre-hospital direct ambulance transfer has led to major improvements in timeliness of ppci in suspected stemi: temporal trends over an eight-year period in a designated PPCI centre
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Z Butt, B McGrath, D Cadogan, I Casserly, H McCann, J O’Neill, E Keelan, P Keelan, J Galvin, B Doyle, and G Blake
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- 2022
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25. The InBetweeners
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Colleen B. Doyle, Sam Blanckensee, Niamh Nestor, and Conor Buggy
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- 2022
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26. Prevalence of carbapenemase genes among carbapenem-nonsusceptible Enterobacterales collected in US hospitals in a five-year period and activity of ceftazidime/avibactam and comparator agents
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Mariana Castanheira, Lalitagauri M Deshpande, Rodrigo E Mendes, Timothy B Doyle, and Helio S Sader
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General Medicine - Abstract
Objectives To evaluate the prevalence of acquired β-lactamase genes and susceptibility profiles of carbapenem-nonsusceptible Enterobacterales (CNSE) clinical isolates collected in US hospitals during a 5-year period. Methods Isolates were susceptibility tested by reference broth microdilution methods. Results were interpreted using CLSI breakpoints. Isolates displaying nonsusceptible MICs for imipenem or meropenem were categorized as CNSE. CNSE isolates were screened for β-lactamase-encoding genes using whole-genome sequencing. New genes were cloned, expressed in an Escherichia coli background and susceptibility tested. Results A total of 450 (1.3%) isolates were CNSE. Klebsiella pneumoniae serine carbapenemase (KPC) production was the most common resistance mechanism among CNSE isolates: 281/450 (62.4%) carried blaKPC, including three new variants. OXA-48-like and metallo-β-lactamase (MBL) encoding genes were detected among seven and 12 isolates, respectively. Among MBL genes, blaNDM-1 was the most common, but blaNDM-5, blaVIM-1 and blaIMP-27 were also identified. 169 (37.6% of the CNSE) isolates did not produce carbapenemases. Ceftazidime/avibactam was the most active agent (95.0% to 100.0% susceptible) against CNSE isolates from all carbapenemase groups except MBL-producing isolates. Ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam inhibited 100.0%, 97.6% and 92.3% of the non-carbapenemase CNSE isolates, respectively. Among the three new blaKPC variants, one conferred resistance to ceftazidime/avibactam and low meropenem MIC results while the other two had profiles similar to blaKPC-2 or blaKPC-3. Conclusions A decline in carbapenemase production was noticed in US hospitals in the 5-year period analysed in this study. New β-lactam/β-lactamase inhibitor combinations tested had good activity against CNSE isolates.
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- 2022
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27. A pilot study investigating feasibility of mainstreaming germline BRCA1 and BRCA2 testing in high-risk patients with breast and/or ovarian cancer in three tertiary Cancer Centres in Ireland
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Terri Patricia McVeigh, Karl J. Sweeney, Donal J. Brennan, Una M. McVeigh, Simon Ward, Ann Strydom, Sheila Seal, Katherine Astbury, Paul Donnellan, Joanne Higgins, Maccon Keane, Michael J. Kerin, Carmel Malone, Pauline McGough, Ray McLaughlin, Michael O’Leary, Margaret Rushe, Michael Kevin Barry, Geraldine MacGregor, Michael Sugrue, Ala Yousif, Dhafir Al-Azawi, Eileen Berkeley, Terence J. Boyle, Elizabeth M. Connolly, Carmel Nolan, Elaine Richardson, Claire Giffney, Samantha B. Doyle, Sheila Broderick, William Boyd, Ruaidhri McVey, Thomas Walsh, Michael Farrell, David J. Gallagher, Nazneen Rahman, and Angela J. George
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Cancer Research ,Oncology ,Genetics ,Genetics (clinical) - Abstract
In the Republic of Ireland (ROI), BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient's BRCA status. "Mainstreaming" BRCA1/BRCA2 testing through routine oncology/surgical clinics has been implemented successfully in other centres in the UK and internationally. We aimed to pilot this pathway in three Irish tertiary centres. A service evaluation project was undertaken over a 6-month period between January and July 2017. Eligible patients, fulfilling pathology and age-based inclusion criteria defined by TGL clinical, were identified, and offered constitutional BRCA1/BRCA2 testing after pre-test counselling by treating clinicians. Tests were undertaken by TGL Clinical. Results were returned to clinicians by secure email. Onward referrals of patients with uncertain/pathogenic results, or suspicious family histories, to Clinical Genetics were made by the treating team. Surveys assessing patient and clinician satisfaction were sent to participating clinicians and a sample of participating patients. Data was collected with respect to diagnostic yield, turnaround time, onward referral rates, and patient and clinician feedback. A total of 101 patients underwent diagnostic germline BRCA1/BRCA2 tests through this pathway. Pathogenic variants were identified in 12 patients (12%). All patients in whom variants were identified were appropriately referred to Clinical Genetics. At least 12 additional patients with uninformative BRCA1/BRCA2 tests were also referred for formal assessment by Clinical Geneticist or Genetic Counsellor. Issues were noted in terms of time pressures and communication of results to patients. Results from a representative sample of participants completing the satisfaction survey indicated that the pathway was acceptable to patients and clinicians. Mainstreaming of constitutional BRCA1/BRCA2 testing guided by age- and pathology-based criteria is potentially feasible for patients with breast cancer as well as patients with ovarian cancer in Ireland.
- Published
- 2022
28. Risk of Juvenile Idiopathic Arthritis and Rheumatoid Arthritis in Patients With Celiac Disease: A Population-Based Cohort Study
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John B. Doyle, Benjamin Lebwohl, Johan Askling, Anders Forss, Peter H.R. Green, Bjorn Roelstraete, Jonas Söderling, and Jonas F. Ludvigsson
- Subjects
Adult ,Cohort Studies ,Arthritis, Rheumatoid ,Celiac Disease ,Hepatology ,Incidence ,Gastroenterology ,Humans ,Child ,Arthritis, Juvenile - Abstract
Celiac disease (CD) is associated with many immune-mediated conditions, but a definitive epidemiological association between CD and juvenile idiopathic arthritis (JIA) or rheumatoid arthritis (RA) has not been established. We quantified the risk of JIA and RA among patients with CD using a population-based cohort.We identified patients diagnosed with biopsy-proven CD between 2004 and 2017 using data from a national histopathology cohort in Sweden. Each patient was matched by age, sex, calendar year, and geographic region to reference individuals in the general population. We calculated the incidence and estimated the relative risk, through Cox proportional hazards models, of JIA in individuals with CD aged18 and of RA in individuals with CD aged ≥18.We identified 24,014 individuals with CD who were matched to 117,397 reference individuals from the general population. Among individuals aged18, the incidence rate of JIA was 5.9 per 10,000 person-years in patients with CD and 2.2 per 10,000 person-years in the general population (n events = 40 and 73, respectively; hazard ratio [HR] 2.68, 95% confidence interval 1.82-3.95) over a follow-up of 7.0 years. Among individuals aged ≥ 18, the incidence of RA was 8.4 per 10,000 person-years in CD and 5.1 per 10,000 person-years in matched comparators (n events = 110 and 322, respectively; HR 1.70, 95% confidence interval 1.36-2.12) over a follow-up of 8.8 years.Among children with CD, JIA develops nearly 3 times as often as it does in the general population, and among adults with CD, RA occurs nearly 2 times as often. Clinicians caring for patients with CD with joint symptoms should have a low threshold to evaluate for JIA or RA.
- Published
- 2022
29. MR-Guided Radiation Therapy With Concurrent Gemcitabine/Nab-Paclitaxel Chemotherapy in Inoperable Pancreatic Cancer: A TITE-CRM Phase I Trial
- Author
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Hyun Kim, Jeffrey R. Olsen, Olga L. Green, Re-I Chin, William G. Hawkins, Ryan C. Fields, Chet Hammill, Majella B. Doyle, William Chapman, Rama Suresh, Benjamin Tan, Katrina Pedersen, Brandi Jansen, Todd A. DeWees, Esther Lu, Lauren E. Henke, Shahed Badiyan, Parag J. Parikh, Michael C. Roach, Andrea Wang-Gillam, and Kian-Huat Lim
- Subjects
Cancer Research ,Radiation ,Oncology ,Radiology, Nuclear Medicine and imaging - Abstract
Ablative radiation therapy for borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BR/LA-PDAC) may limit concurrent chemotherapy dosing and usually is only safely deliverable to tumors distant from gastrointestinal organs. Magnetic resonance guided radiation therapy may safely permit radiation and chemotherapy dose escalation.We conducted a single-arm phase I study to determine the maximum tolerated dose of ablative hypofractionated radiation with full-dose gemcitabine/nab-paclitaxel in patients with BR/LA-PDAC. Patients were treated with gemcitabine/nab-paclitaxel (1000/125 mg/mThirty patients enrolled (March 2015-February 2019), with 26 evaluable patients (2 progressed before radiation, 1 was determined ineligible for radiation during planning, 1 withdrew consent). One DLT was observed. The DLT rate was 14.1% (3.3%-24.9%) with a maximum tolerated dose of gemcitabine/nab-paclitaxel (1000/100 mg/mFull-dose gemcitabine/nab-paclitaxel with ablative magnetic resonance guided radiation therapy dosing is safe in patients with BR/LA-PDAC, with promising LPFS and DMFS.
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- 2022
30. Endoscopic Ultrasound-Guided Biliary Drainage
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John B. Doyle and Amrita Sethi
- Subjects
General Medicine - Abstract
Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD) are currently first- and second-line therapeutic options, respectively, for the relief of biliary obstruction. In recent years, however, endoscopic ultrasound-guided biliary drainage (EUS-BD) has become an established alternative therapy for biliary obstruction. There are multiple different techniques for EUS-BD, which can be distinguished based on the access point within the biliary tree (intrahepatic versus extrahepatic) and the location of stent placement (transenteric versus transpapillary). The clinical and technical success rates of biliary drainage for EUS-BD are similar to both ERCP and PTBD, and complication rates are favorable for EUS-BD relative to PTBD. As EUS-BD becomes more widely practiced and endoscopic tools continue to advance, the outcomes will likely improve, and the breadth of indications for EUS-BD will continue to expand.
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- 2023
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31. Ten Years of Green Manuring and Biofumigation Alters Soil Characteristics and Microbiota
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Brianna A.R. Walker, Shane M. Powell, Robert S. Tegg, Richard B. Doyle, Ian G. Hunt, and Calum R. Wilson
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History ,Ecology ,Polymers and Plastics ,Soil Science ,Business and International Management ,Agricultural and Biological Sciences (miscellaneous) ,Industrial and Manufacturing Engineering - Published
- 2022
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32. In Vitro Selection of Enterobacter cloacae with Cefepime, Meropenem, and Ceftazidime-Avibactam Generates Diverse Resistance Mechanisms
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Mariana Castanheira, Jill Lindley, Timothy B. Doyle, Andrew P. Davis, and Helio S. Sader
- Subjects
Microbiology (medical) ,Infectious Diseases ,Pharmacology (medical) ,General Medicine - Abstract
We submitted 5 E. cloacae isolates to 10-day serial passage in broth microdilution with cefepime, meropenem, or ceftazidime-avibactam to evaluate MIC increases and resistance mechanisms after exposure. Post-exposure isolates displaying2-fold changes from the parent isolate were analyzed alongside their parent isolate. Overall increase is MIC results of 4- to 256-fold (median: 16-fold) were noted after cefepime exposure, 16- to 128-fold (64-fold) after meropenem, and 2- to 32-fold (8-fold) after ceftazidime-avibactam. Post-exposure isolates had diverse mechanisms identified using a combination of short- and long-whole genome sequencing. All agents selected for AmpC alterations in one isolate set. OmpC and TetA/AcrR regulator alterations were noted in meropenem and ceftazidime-avibactam post-exposure isolates of the same set. Other mutations in AmpC were noted when isolates were exposed to cefepime or ceftazidime-avibactam. A premature stop codon in the cell division inhibitor protein MioC was observed when one parent isolate was exposed to any of the agents, suggesting a cell persistence mechanism. Mutations in less common transporter systems and protein synthesis components were also noted. Cross-resistance to other β-lactams occurred with all agents and resistance mechanisms were diverse with some not usually associated with β-lactam resistance in Enterobacterales. This initial evaluation suggests that cefepime and meropenem select for isolates with higher MIC values when compared to ceftazidime-avibactam. Further studies evaluating these findings should be performed for other species for which the primary β-lactam resistance mechanism is not gene acquisition. These studies should evaluate these observations in vivo to evaluate their translation into patient treatment policies.
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- 2023
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33. Soil microbial community dynamics during ryegrass green manuring and brassica biofumigation
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Brianna A.R. Walker, Shane M. Powell, Robert S. Tegg, Richard B. Doyle, Ian G. Hunt, and Calum R. Wilson
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Ecology ,Soil Science ,Agricultural and Biological Sciences (miscellaneous) - Published
- 2022
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34. Best Practices and Strategies for Online Instructors : Insights From Higher Education Online Faculty
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Lori B. Doyle, Tanya M. Tarbutton, Lori B. Doyle, and Tanya M. Tarbutton
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- Web-based instruction. | Education,
- Published
- 2024
35. Nutritional management of mitochondrial depletion syndrome: a case study
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J.B. Freemantle, B. Doyle, D. MacCallum, P. Young, and M.A. Thomson
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Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism - Published
- 2022
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36. Fluvoxamine for the treatment of COVID-19
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Michael G Dodds, Eileen B Doyle, Angela M Reiersen, Fran Brown, and Craig R Rayner
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Fluvoxamine ,SARS-CoV-2 ,Humans ,General Medicine ,COVID-19 Drug Treatment - Published
- 2022
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37. Effects of Social Housing on Dairy Calf Social Bonding
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Emily E. Lindner, Katie N. Gingerich, Katharine C. Burke, Samantha B. Doyle, and Emily K. Miller-Cushon
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social housing ,social bonding ,social preference ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
Social housing for dairy calves has a range of benefits for social development, yet there is limited understanding of how social bonds form early in life. We characterized effects of early life social contact on the development of social preference for calves varying in familiarity. A total of 40 calves were tested in a social preference test at 4 weeks of age to assess the formation of social bonds and preference for their peers. Within an open-field social preference test, focal calves were presented with two stimulus calves, one ‘more familiar’ and one ‘less familiar’. We found that pair-housed calves spent more time in close proximity with either stimulus calf and had a greater preference for their pen-mate, compared to another calf reared within visual contact. Individually housed calves exhibited no preference for calves reared within visual but not physical contact compared to calves that were completely unfamiliar. Of the calves that approached both stimulus calves, individually housed calves that approached the ‘less familiar’ calf first spent less time near the ‘more familiar’ calf, whereas behavior of pair-housed calves was not affected by the first calf approached. These results suggest that physical contact is necessary for the development of social bonds in young dairy calves, and early life social housing may support the development of normal social behavior in dairy cattle.
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- 2022
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38. Dorsal root ganglion toxicity after AAV intra-CSF delivery of a RNAi expression construct into non-human primates and mice.
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Hawley ZCE, Pardo ID, Cao S, Zavodszky MI, Casey F, Ferber K, Luo Y, Hana S, Chen SK, Doherty J, Costa R, Cullen P, Liu Y, Carlile TM, Chowdhury T, Doyle B, Clarner P, Mangaudis K, Guilmette E, Bourque S, Koske D, Nadella MVP, Trapa P, Hawes ML, Raitcheva D, and Lo SC
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- Animals, Mice, Superoxide Dismutase-1 genetics, Humans, Neurons metabolism, Male, Dependovirus genetics, MicroRNAs genetics, Ganglia, Spinal metabolism, Genetic Vectors administration & dosage, Genetic Vectors genetics, RNA Interference
- Abstract
Dorsal root ganglion (DRG) toxicity has been consistently reported as a potential safety concern after delivery of adeno-associated viruses (AAVs) containing gene-replacement vectors but has yet to be reported for RNAi-based vectors. Here, we report DRG toxicity after AAV intra-CSF delivery of an RNAi expression construct-artificial microRNA targeting superoxide dismutase 1 (SOD1)-in non-human primates (NHPs) and provide evidence that this can be recapitulated within mice. Histopathology evaluation showed that NHPs and mice develop DRG toxicity after AAV delivery, including DRG neuron degeneration and necrosis and nerve-fiber degeneration that were associated with increases in cerebrospinal fluid (CSF) and serum phosphorylated neurofilament heavy chain (pNF-H). RNA-sequencing analysis of DRGs showed that dysregulated pathways were preserved between NHPs and mice, including increases in innate/adaptive immune responses and decreases in mitochondrial- and neuronal-related genes, following AAV treatment. Finally, endogenous miR-21-5p was upregulated in DRGs of AAV-treated NHPs and mice. Increases in miR-21-5p were also identified within the CSF of NHPs, which significantly correlated with pNF-H, implicating miR-21-5p as a potential biomarker of DRG toxicity in conjunction with other molecular analytes. This work highlights the importance of assessing safety concerns related to DRG toxicity when developing RNAi-based AAV vectors for therapeutic purposes., Competing Interests: Declaration of interests M.L.H. is a paid advisor from Charter Preclinical Services. All other authors are or were paid employees at Biogen., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2025
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39. Extra-adrenal adrenocortical cancer associated with multiple endocrine neoplasia type 1.
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Green D, Richards K, Doyle B, Thompson C, Hill A, O'Reilly MW, and Sherlock M
- Abstract
Summary: Adrenocortical carcinoma (ACC) is a rare malignant tumour arising from the adrenal cortex, with an estimated annual incidence of one to two patients per million. Ectopic ACCs are extremely rare. The majority of ACCs are sporadic; however, ACC has been linked with genetic disease processes, including multiple endocrine neoplasia type-1 (MEN-1). We present the case of a 66-year-old lady referred with newly diagnosed diabetes on a background of primary hyperparathyroidism. Examination revealed Cushingoid features, and hormonal evaluation confirmed ACTH-independent Cushing's syndrome. Morning cortisol after a 1 mg overnight dexamethasone suppression test was 548 nmol/L with an undetectable ACTH <3.0 pg/mL. Dehydroepiandrosterone sulphate was 5.3 μmol/L and androstenedione 3.49 nmol/L, both of which were normal. Testosterone was suppressed at <0.4 nmol/L. Imaging revealed a 6 × 6 × 4.5 cm right-sided presumed adrenal lesion, a pancreatic lesion (2.5 × 1.6 cm), and bilateral pulmonary nodules (0.9 × 0.8 cm, 0.7 × 0.6 cm, 0.3 cm). Right adrenalectomy was performed, and histology was consistent with an extra-adrenal ACC (Weiss score 5/9) within the peri-adrenal adipose tissue. The resected adrenal gland was normal. Lung biopsy confirmed metastatic ACC tissue, and endoscopic ultrasound-guided biopsy of the pancreatic lesion revealed a pancreatic neuroendocrine tumour, which was confirmed biochemically to be an insulinoma. Genetic assessment confirmed MEN-1. This case highlights the importance of screening for MEN-1 in at-risk patients and the need for close clinical follow-up. To our knowledge, this is the first case report of extra-adrenal ACC in MEN-1 syndrome., Learning Points: Adrenal lesions in MEN-1 syndrome have significant malignant potential. Newly diagnosed lesions should be followed closely with short-interval imaging, and a lower threshold for surgical removal is suggested. Primary hyperparathyroidism is often the earliest laboratory or clinical manifestation of MEN-1 syndrome. A detailed medical and family history is vital in order to appropriately identify patients at risk of MEN-1. To our knowledge, this is the first case report of extra-adrenal adrenocortical carcinoma in MEN-1 syndrome.
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- 2024
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40. An unusual case of nephrotic syndrome.
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Wildes DM, Fitzsimons A, Doyle B, Green A, Sweeney C, and Awan A
- Subjects
- Humans, Female, Adolescent, Biopsy, Kidney pathology, Glomerulosclerosis, Focal Segmental genetics, Glomerulosclerosis, Focal Segmental diagnosis, Glomerulosclerosis, Focal Segmental pathology, Glomerulosclerosis, Focal Segmental complications, Glomerulosclerosis, Focal Segmental drug therapy, Mutation, Nephrotic Syndrome genetics, Nephrotic Syndrome diagnosis, Nephrotic Syndrome complications, Nephrotic Syndrome drug therapy, Collagen Type IV genetics, Nephritis, Hereditary genetics, Nephritis, Hereditary complications, Nephritis, Hereditary diagnosis, Nephritis, Hereditary pathology
- Abstract
Background: Alport syndrome is a genetically heterogenous disorder resulting from variants in genes coding for alpha-3/4/5 chains of Collagen IV, which results in defective basement membranes in the kidney, cochlea and eye. The syndrome has different inheritance patterns and historically, was thought of as a disease affecting solely males., Case: A 15-year-old female presented with pedal oedema, hypertension and proteinuria. She underwent a kidney biopsy which showed findings in keeping with focal segmental glomerulosclerosis. Her condition was refractory to steroids. Steroid-resistant nephrotic syndrome genetics were sent, revealing a rare pathogenic variant in the COL4A5 gene., Conclusion: Heterozygous females with X-linked Alport syndrome can develop chronic kidney disease and hearing loss. Clinicians should be mindful when reviewing kidney histology to include Alport syndrome as a differential for female patients. COL4A3-5 genes should be included in all steroid-resistant nephrotic syndrome genetic panels., (© 2024. The Author(s).)
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- 2024
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41. A systems approach to managing the risk of healthcare acquired infection in an acute hospital setting supported by human factors ergonomics, data science, data governance and AI.
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Ward ME, Geary U, Brennan R, Vining R, McKenna L, O'Connell B, Bergin C, Byrne D, Creagh D, Fogarty M, Healy U, McDonald G, Ebiele M, Crane M, Pham MK, Bendechache M, Bezbradica M, Liang J, Doyle B, Guilfoyle J, Shuhaiber A, and McDonald N
- Abstract
Innovative approaches are needed for managing risk and system change in healthcare. This paper presents a case study of a project that took place over two years, taking a systems approach to managing the risk of healthcare acquired infection in an acute hospital setting, supported by an Access Risk Knowledge Platform which brings together Human Factors Ergonomics, Data Science, Data Governance and AI expertise. Evidence for change including meeting notes and use of the platform were studied. The work on the project focused on first systematically building a rich picture of the current situation from a transdisciplinary perspective. This allowed for understanding risk in context and developing a better capability to support enterprise risk management and accountability. From there a linking of operational and risk data took place which led to mapping of the risk pattern in the hospital.
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- 2024
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42. Implementation of a national monitoring programme of Campylobacter in Irish broilers to measure progress of on-farm and primary processing control measures.
- Author
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Golden O, Gutierrez M, O'Flaherty J, Unger K, Doyle B, Keogh T, McLernon J, Pearce R, O'Brien T, and Byrne W
- Subjects
- Animals, Ireland epidemiology, Animal Husbandry methods, Food Microbiology, Farms, Humans, Chickens microbiology, Campylobacter isolation & purification, Poultry Diseases microbiology, Poultry Diseases epidemiology, Poultry Diseases prevention & control, Campylobacter Infections veterinary, Campylobacter Infections epidemiology, Campylobacter Infections prevention & control, Campylobacter Infections microbiology
- Abstract
Background: Campylobacter is the most common food-borne pathogen in the European Union. In 2018, the crude incidence rate in Ireland was 63.6 per 100,000 population. Chicken is considered an important source of infection for humans. In 2015, the Campylobacter Stakeholders' Group (CSG) was established to reduce Campylobacter contamination levels in Irish broiler flocks., Aims: This work aimed to describe the Campylobacter monitoring programme that was established by the CSG, to analyse the results of this testing between 2019 and 2022, and to assess progress., Methods and Results: This paper describes the monitoring programme that was established by the CSG, which harmonized Campylobacter enumeration testing across all Irish broiler processors and allowed comparability of results for trend analysis. An analysis of the 2019-2022 data is presented here and compared to previous studies of Campylobacter levels in Irish broilers. An analysis of the 2019-2022 data showed a significant reduction in levels in both caeca and neck skin when the results from 2022 were compared to those from 2019 to 2020. Campylobacter spp. were detected in 37% of caecal samples from first depopulation (pre-thin) broilers and 30% of neck skin samples in 2022, with just 4% of carcases (in neck skin samples) with ≥1000 colony-forming units per gram detected in 2022. Campylobacter levels detected in Irish broilers, in the present monitoring programme were less than those reported in previous studies in both caecal and carcase samples, although not directly comparable for statistical significance because of differences in study methods., Conclusions: The cooperation between stakeholders and regulators of the Irish broiler chicken industry over the past decade has facilitated a coordinated approach to monitoring of Campylobacter levels in broilers, and implementation of control measures. This has enabled a steady reduction in the levels of Campylobacter in Irish chicken., (© 2024 Wiley‐VCH GmbH.)
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- 2024
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43. Author Correction: Quantifying bias introduced by sample collection in relative and absolute microbiome measurements.
- Author
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Maghini DG, Dvorak M, Dahlen A, Roos M, Doyle B, Kuersten S, and Bhatt AS
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- 2024
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44. "This is it…this is our normal" - the voices of family members and first responders experiencing duty-related trauma in Ireland.
- Author
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Traynor A, Doyle B, Eppich W, Tjin A, Mulhall C, and O'Toole M
- Subjects
- Humans, Ireland, Male, Female, Adult, Middle Aged, Community-Based Participatory Research, Stress, Psychological psychology, Family psychology, Qualitative Research, Focus Groups, Emergency Responders psychology
- Abstract
Background: Compared to other occupational groups, first responders (FR) experience worse mental health outcomes due to duty-related trauma and occupational stressors. Despite their best efforts, they bring this stress home to friends and family. Consequently, FR and their supporters suffer from increased psychosocial difficulties and experience stigma and other barriers to help-seeking. Prior work offers little opportunity for open dialogue and shared understanding of the repercussions of this occupation for all members of the first responder community. In this qualitative study, we aimed to: (i) explore the lived experience of Irish FR and their family members (FM) related to occupational stressors, and (ii) identify opportunities to engage FM with existing organizational supports available for FR., Methods: Using a community based participatory research (CBPR) approach, we conducted six focus groups involving a total of fourteen participants comprising FR, organizational representatives, and FM. All focus groups were audio recorded, transcribed, and analyzed using reflexive thematic analysis., Findings: FR and FM shared their experiences of both joining and learning to live as members of the FR community in Ireland. Through our analysis, we identified a main theme of 'crossing thresholds', characterizing their transformative learning experiences. This learning experience includes recognizing the consequences of this new role for them as individuals and for their relationships. Participants also shared how they have learned to cope with the consequences of their roles and what they need to better support each other., Conclusions: FM are often unheard, hidden members of the first responder community in Ireland, highlighting an unmet need for FR organizations to acknowledge FM role in supporting FR and to provide them with the appropriate training and resources required. Training for new recruits needs to move beyond the tokenistic involvement of FM and encourage knowledge sharing among experienced and novice members. Cultural change is required to support help-seeking among FR and foster a sense of peer support and community among families., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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45. A Novel Monoallelic ALG5 Variant Causing Late-Onset ADPKD and Tubulointerstitial Fibrosis.
- Author
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Elhassan EAE, Kmochová T, Benson KA, Fennelly NK, Barešová V, Kidd K, Doyle B, Dorman A, Morrin MM, Kyne NC, Vyleťal P, Hartmannová H, Hodaňová K, Sovová J, Mušálková D, Vrbacká A, Přistoupilová A, Živný J, Svojšová K, Radina M, Stránecký V, Loginov D, Pompach P, Novák P, Vaníčková Z, Hansíková H, Rajnochová-Bloudíčková S, Viklický O, Hůlková H, Cavalleri GL, Hnízda A, Bleyer AJ, Kmoch S, Conlon PJ, and Živná M
- Abstract
Introduction: Monoallelic variants in the ALG5 gene encoding asparagine-linked glycosylation protein 5 homolog (ALG5) have been recently shown to disrupt polycystin-1 (PC1) maturation and trafficking via underglycosylation, causing an autosomal dominant polycystic kidney disease-like (ADPKD-like) phenotype and interstitial fibrosis. In this report, we present clinical, genetic, histopathologic, and protein structure and functional correlates of a new ALG5 variant, p.R79W, that we identified in 2 distant genetically related Irish families displaying an atypical late-onset ADPKD phenotype combined with tubulointerstitial damage., Methods: Whole exome and targeted sequencing were used for segregation analysis of available relatives. This was followed by immunohistochemistry examinations of kidney biopsies, and targeted (UMOD, MUC1) and untargeted plasma proteome and N-glycomic studies., Results: We identified a monoallelic ALG5 variant [GRCh37 (NM_013338.5): g.37569565G>A, c.235C>T; p.R79W] that cosegregates in 23 individuals, of whom 18 were clinically affected. We detected abnormal localization of ALG5 in the Golgi apparatus of renal tubular cells in patients' kidney specimens. Further, we detected the pathological accumulation of uromodulin, an N-glycosylated glycosylphosphatidylinositol (GPI)-anchored protein, in the endoplasmic reticulum (ER), but not mucin-1, an O- and N-glycosylated protein. Biochemical investigation revealed decreased plasma and urinary uromodulin levels in clinically affected individuals. Proteomic and glycoproteomic profiling revealed the dysregulation of chronic kidney disease (CKD)-associated proteins., Conclusion: ALG5 dysfunction adversely affects maturation and trafficking of N-glycosylated and GPI anchored protein uromodulin, leading to structural and functional changes in the kidney. Our findings confirm ALG5 as a cause of late-onset ADPKD and provide additional insight into the molecular mechanisms of ADPKD- ALG5 ., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)
- Published
- 2024
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46. Quantifying bias introduced by sample collection in relative and absolute microbiome measurements.
- Author
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Maghini DG, Dvorak M, Dahlen A, Roos M, Doyle B, Kuersten S, and Bhatt AS
- Subjects
- Feces, RNA, Ribosomal, 16S genetics, Metagenome, DNA, Microbiota genetics
- Abstract
To gain insight into the accuracy of microbial measurements, it is important to evaluate sources of bias related to sample condition, preservative method and bioinformatic analyses. There is increasing evidence that measurement of the total count and concentration of microbes in the gut, or 'absolute abundance', provides a richer source of information than relative abundance and can correct some conclusions drawn from relative abundance data. However, little is known about how preservative choice can affect these measurements. In this study, we investigated how two common preservatives and short-term storage conditions impact relative and absolute microbial measurements. OMNIgene GUT OMR-200 yields lower metagenomic taxonomic variation between different storage temperatures, whereas Zymo DNA/RNA Shield yields lower metatranscriptomic taxonomic variation. Absolute abundance quantification reveals two different causes of variable Bacteroidetes:Firmicutes ratios across preservatives. Based on these results, we recommend OMNIgene GUT OMR-200 preservative for field studies and Zymo DNA/RNA Shield for metatranscriptomics studies, and we strongly encourage absolute quantification for microbial measurements., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2024
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47. UV-C Light Intervention as a Barrier against Airborne Transmission of SARS-CoV-2.
- Author
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Ragan I, Perez J, Davenport W, Hartson L, and Doyle B
- Subjects
- Animals, Cricetinae, Humans, Respiratory Aerosols and Droplets, SARS-CoV-2, Mesocricetus, Public Health, COVID-19 prevention & control
- Abstract
Background: SARS-CoV-2 continues to impact human health globally, with airborne transmission being a significant mode of transmission. In addition to tools like vaccination and testing, countermeasures that reduce viral spread in indoor settings are critical. This study aims to assess the efficacy of UV-C light, utilizing the Violett sterilization device, as a countermeasure against airborne transmission of SARS-CoV-2 in the highly susceptible Golden Syrian hamster model., Methods: Two cohorts of naïve hamsters were subjected to airborne transmission from experimentally infected hamsters; one cohort was exposed to air treated with UV-C sterilization, while the other cohort was exposed to untreated air., Results: Treatment of air with UV-C light prevented the airborne transmission of SARS-CoV-2 from the experimentally exposed hamster to naïve hamsters. Notably, this protection was sustained over a multi-day exposure period during peak viral shedding by hamsters., Conclusions: These findings demonstrate the efficacy of the UV-C light to mitigate against airborne SARS-CoV-2 transmission. As variants continue to emerge, UV-C light holds promise as a tool for reducing infections in diverse indoor settings, ranging from healthcare facilities to households. This study reinforces the urgency of implementing innovative methods to reduce airborne disease transmission and safeguard public health against emerging biological threats.
- Published
- 2024
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48. S.P.O.R.R.T.-A Comprehensive Approach to the Assessment and Non-Operative Management of Overuse Knee Conditions in Youth Athletes.
- Author
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Davis J, Doyle B, Ishii H, and Jayanthi N
- Abstract
Purpose of Review: The evaluation of a young athlete with an overuse injury to the knee involves a comprehensive approach. There are a number of elements to consider including assessments of skeletal maturity (biologic maturation), workload (training load + competition load), sport specialization status, and biomechanics. The type of injury and treatment, as well as future prognosis, may be influenced by these and other factors., Recent Findings: Calculating the percentage of predicted adult height (PPAH) is a valuable tool in assessing overuse injury patterns and diagnoses in youth athletes. Modifiable and non-modifiable overuse injury risk factors require monitoring from clinicians as young athletes mature and develop over time. Training and rehabilitation programs should be adapted to account for these. In this manuscript, we seek to introduce a novel, comprehensive approach: S.P.O.R.R.T. (Skeletal Maturity, Prior Injury Risk, One Sport Specialization, Rehabilitation, Return to Play, Training Recommendations) (Fig. 1). Overuse, non-traumatic injuries to the knee in youth athletes will be presented in a case-based and evidence-based model to provide a framework for a comprehensive approach to the assessment and treatment of youth athletes with overuse injuries., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2023
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49. Population Health Projects: An Innovative Teaching Strategy for Baccalaureate Nursing Education.
- Author
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Beiers-Jones K, Doyle B, Lanciotti K, and Lemon E
- Subjects
- Humans, Learning, Curriculum, Education, Nursing, Baccalaureate, Education, Nursing, Students, Nursing
- Abstract
The American Association of Colleges of Nursing (AACN) Core Competencies for Professional Nursing Education (2021) include a Population Health domain. Future nurses well-versed in the social determinants of health are poised to be leaders, creating change to improve the lives of vulnerable populations. The Population Health Project (PHP) is an innovative learning experience, immersing student nurses in authentic interactions that impact the communities they partner with. Baccalaureate nursing students, during their Population Health course, work in groups to produce innovative, community-focused PHPs, successfully incorporating the AACN competencies. Students identify issues impacting the wellbeing of their assigned population; these issues become the focus of their PHP. They engage with community stakeholders, including their patients, policy makers, and community partners to develop evidence-based and sustainable projects. PHPs focus on reducing health disparities and address priorities important to communities, including concepts of diversity, inclusion, and equity. Examples of long-term impacts of PHPs include: legislative change - a new law mandating pharmacies provide prescription labels in a language the patient can understand; innovative policies - initiating efforts to create a hospice for unhoused patients; and new service provision programs - teaming with a fire department to co-develop a home-visiting program to reduce non-emergent 911 calls., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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50. Immobilised-enzyme microreactors for the identification and synthesis of conjugated drug metabolites.
- Author
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Doyle B, Madden LA, Pamme N, and Jones HS
- Abstract
The study of naturally circulating drug metabolites has been a focus of interest, since these metabolites may have different therapeutic and toxicological effects compared to the parent drug. The synthesis of metabolites outside of the human body is vital in order to conduct studies into the pharmacological activities of drugs and bioactive compounds. Current synthesis methods require significant purification and separation efforts or do not provide sufficient quantities for use in pharmacology experiments. Thus, there is a need for simple methods yielding high conversions whilst bypassing the requirement for a separation. Here we have developed and optimised flow chemistry methods in glass microfluidic reactors utilising surface-immobilised enzymes for sulfonation (SULT1a1) and glucuronidation (UGT1a1). Conversion occurs in flow, the precursor and co-factor are pumped through the device, react with the immobilised enzymes and the product is then simply collected at the outlet with no separation from a complex biological matrix required. Conversion only occurred when both the correct co-factor and enzyme were present within the microfluidic system. Yields of 0.97 ± 0.26 μg were obtained from the conversion of resorufin into resorufin sulfate over 2 h with the SULT1a1 enzyme and 0.47 μg of resorufin glucuronide over 4 h for UGT1a1. This was demonstrated to be significantly more than static test tube reactions at 0.22 μg (SULT1a1) and 0.19 μg (UGT1a1) over 4 h. With scaling out and parallelising, useable quantities of hundreds of micrograms for use in pharmacology studies can be synthesised simply., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)
- Published
- 2023
- Full Text
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