30 results on '"Earle, E."'
Search Results
2. Final Design and Analysis of the Superconducting Magnets for the Material Plasma Exposure Experiment
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Earle E. Burkhardt, Robert C. Duckworth, Arnold Lumsdaine, Michael Kaufman, Juergen Rapp, Phillip Ferguson, Richard Goulding, Thomas Bjorholm, Simon Keys, Rory Warner, Stuart Hawkins, Oliver Levantine, and Johannes van Oort
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Electrical and Electronic Engineering ,Condensed Matter Physics ,Electronic, Optical and Magnetic Materials - Published
- 2023
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3. Final Design and Analysis of the Superconducting Magnets for the Material Plasma Exposure Experiment
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Burkhardt, Earle E., primary, Duckworth, Robert C., additional, Lumsdaine, Arnold, additional, Kaufman, Michael, additional, Rapp, Juergen, additional, Ferguson, Phillip, additional, Goulding, Richard, additional, Bjorholm, Thomas, additional, Keys, Simon, additional, Warner, Rory, additional, Hawkins, Stuart, additional, Levantine, Oliver, additional, and van Oort, Johannes, additional
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- 2023
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4. Postoperative pulmonary complications in adult surgical patients in low- to middle-income countries: a systematic review and meta-analysis.
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Earle, E., Turton, E. W., and Rodseth, R. N.
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MIDDLE-income countries , *SURGICAL complications , *LENGTH of stay in hospitals , *HIGH-income countries ,MORTALITY risk factors - Abstract
Background: After surgery, patients are at risk of developing postoperative pulmonary complications (PPCs). Our current understanding of PPCs is based on data from high-income countries (HICs). Methods: A systematic review and meta-analysis was conducted to evaluate the incidence of PPCs in adult postsurgical patients from low- to middle-income countries (LMICs). The protocol was registered on the PROSPERO database (CRD42020212932). The search strategy was performed in 2021 on several electronic databases. Studies were assessed for risk of bias with the modified Newcastle-Ottawa Scale. Forest plots of the event rate for the incidence of PPCs and factors associated with PPCs were created. Results: The search strategy identified 1 052 records. Fifteen studies were included in the final review (total of 4 873 participants). Five studies were of high methodological quality. The overall pooled event rate for the incidence of PPCs was 22.4% (95% confidence interval (CI), 15.76-30.78%). In-hospital mortality in patients who developed PPCs was 33.1%. PPCs were identified as a risk factor for in-hospital mortality (odds ratio (OR) 18.2, CI 11.01-30.09). Insufficient outcome data were available to determine the association of PPCs between elective versus emergency surgery, and cardiothoracic versus non-cardiothoracic surgery. Advanced age was associated with the development of PPCs (MD 4.7, 95% CI 0.63-8.7). Male sex was associated with the development of PPCs (OR 1.5, 95% CI 1.17-2.02). PPCs were associated with increased length of hospital stay (mean difference (MD) 6.5, 95% CI 4.04-8.96). Conclusion: The incidence of PPCs was 22.4% following surgery in adult patients in LMICs and was influenced by differences in the definitions of PPCs used. PPCs were identified as a risk factor for in-hospital mortality. Data on the type of surgery and patient characteristics were poorly reported. Further research on PPCs in LMICs is needed to provide granular data for future use. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Depatuxizumab mafodotin in EGFR-amplified newly diagnosed glioblastoma: A phase III randomized clinical trial
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Andrew B Lassman, Stephanie L Pugh, Tony J C Wang, Kenneth Aldape, Hui K Gan, Matthias Preusser, Michael A Vogelbaum, Erik P Sulman, Minhee Won, Peixin Zhang, Golnaz Moazami, Marian S Macsai, Mark R Gilbert, Earle E Bain, Vincent Blot, Peter J Ansell, Suvajit Samanta, Madan G Kundu, Terri S Armstrong, Jeffrey S Wefel, Clemens Seidel, Filip Y de Vos, Sigmund Hsu, Andrés F Cardona, Giuseppe Lombardi, Dmitry Bentsion, Richard A Peterson, Craig Gedye, Véronique Bourg, Antje Wick, Walter J Curran, and Minesh P Mehta
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Cancer Research ,Oncology ,Neurology (clinical) - Abstract
Background Approximately 50% of newly diagnosed glioblastomas (GBMs) harbor epidermal growth factor receptor gene amplification (EGFR-amp). Preclinical and early-phase clinical data suggested efficacy of depatuxizumab mafodotin (depatux-m), an antibody–drug conjugate comprised of a monoclonal antibody that binds activated EGFR (overexpressed wild-type and EGFRvIII-mutant) linked to a microtubule-inhibitor toxin in EGFR-amp GBMs. Methods In this phase III trial, adults with centrally confirmed, EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo. Corneal epitheliopathy was treated with a combination of protocol-specified prophylactic and supportive measures. There was 85% power to detect a hazard ratio (HR) ≤0.75 for overall survival (OS) at a 2.5% 1-sided significance level (ie traditional two-sided p ≤ 0.05) by log-rank testing. Results There were 639 randomized patients (median age 60, range 22–84; 62% men). Prespecified interim analysis found no improvement in OS for depatux-m over placebo (median 18.9 vs. 18.7 months, HR 1.02, 95% CI 0.82–1.26, 1-sided p = 0.63). Progression-free survival was longer for depatux-m than placebo (median 8.0 vs. 6.3 months; HR 0.84, 95% confidence interval [CI] 0.70–1.01, p = 0.029), particularly among those with EGFRvIII-mutant (median 8.3 vs. 5.9 months, HR 0.72, 95% CI 0.56–0.93, 1-sided p = 0.002) or MGMT unmethylated (HR 0.77, 95% CI 0.61–0.97; 1-sided p = 0.012) tumors but without an OS improvement. Corneal epitheliopathy occurred in 94% of depatux-m-treated patients (61% grade 3–4), causing 12% to discontinue. Conclusions Interim analysis demonstrated no OS benefit for depatux-m in treating EGFR-amp newly diagnosed GBM. No new important safety risks were identified.
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- 2022
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6. Depatuxizumab-mafodotin in EGFR-amplified newly diagnosed glioblastoma: a phase III randomized clinical trial
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MS Medische Oncologie, Cancer, Lassman, Andrew B, Pugh, Stephanie L, Wang, Tony J C, Aldape, Kenneth, Gan, Hui K, Preusser, Matthias, Vogelbaum, Michael A, Sulman, Erik P, Won, Minhee, Zhang, Peixin, Moazami, Golnaz, Macsai, Marian S, Gilbert, Mark R, Bain, Earle E, Blot, Vincent, Ansell, Peter J, Samanta, Suvajit, Kundu, Madan G, Armstrong, Terri S, Wefel, Jeffrey S, Seidel, Clemens, de Vos, Filip Y, Hsu, Sigmund, Cardona, Andrés F, Lombardi, Giuseppe, Bentsion, Dmitry, Peterson, Richard A, Gedye, Craig, Bourg, Véronique, Wick, Antje, Curran, Walter J, Mehta, Minesh P, MS Medische Oncologie, Cancer, Lassman, Andrew B, Pugh, Stephanie L, Wang, Tony J C, Aldape, Kenneth, Gan, Hui K, Preusser, Matthias, Vogelbaum, Michael A, Sulman, Erik P, Won, Minhee, Zhang, Peixin, Moazami, Golnaz, Macsai, Marian S, Gilbert, Mark R, Bain, Earle E, Blot, Vincent, Ansell, Peter J, Samanta, Suvajit, Kundu, Madan G, Armstrong, Terri S, Wefel, Jeffrey S, Seidel, Clemens, de Vos, Filip Y, Hsu, Sigmund, Cardona, Andrés F, Lombardi, Giuseppe, Bentsion, Dmitry, Peterson, Richard A, Gedye, Craig, Bourg, Véronique, Wick, Antje, Curran, Walter J, and Mehta, Minesh P
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- 2023
7. Depatuxizumab mafodotin in EGFR-amplified newly diagnosed glioblastoma: A phase III randomized clinical trial
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Lassman, Andrew B, primary, Pugh, Stephanie L, additional, Wang, Tony J C, additional, Aldape, Kenneth, additional, Gan, Hui K, additional, Preusser, Matthias, additional, Vogelbaum, Michael A, additional, Sulman, Erik P, additional, Won, Minhee, additional, Zhang, Peixin, additional, Moazami, Golnaz, additional, Macsai, Marian S, additional, Gilbert, Mark R, additional, Bain, Earle E, additional, Blot, Vincent, additional, Ansell, Peter J, additional, Samanta, Suvajit, additional, Kundu, Madan G, additional, Armstrong, Terri S, additional, Wefel, Jeffrey S, additional, Seidel, Clemens, additional, de Vos, Filip Y, additional, Hsu, Sigmund, additional, Cardona, Andrés F, additional, Lombardi, Giuseppe, additional, Bentsion, Dmitry, additional, Peterson, Richard A, additional, Gedye, Craig, additional, Bourg, Véronique, additional, Wick, Antje, additional, Curran, Walter J, additional, and Mehta, Minesh P, additional
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- 2022
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8. Depatuxizumab mafodotin in EGFR-amplified newly diagnosed glioblastoma: A phase III randomized clinical trial.
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Lassman, Andrew B, Pugh, Stephanie L, Wang, Tony J C, Aldape, Kenneth, Gan, Hui K, Preusser, Matthias, Vogelbaum, Michael A, Sulman, Erik P, Won, Minhee, Zhang, Peixin, Moazami, Golnaz, Macsai, Marian S, Gilbert, Mark R, Bain, Earle E, Blot, Vincent, Ansell, Peter J, Samanta, Suvajit, Kundu, Madan G, Armstrong, Terri S, and Wefel, Jeffrey S
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- 2023
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9. Effect of Internal and Bulge Loops on the Thermal Stability of Small DNA Duplexes.
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Stellwagen E, Barnard PJ, and Stellwagen NC
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- Temperature, Nucleic Acid Conformation, Electrophoresis, Capillary, Sodium chemistry, Potassium chemistry, Transition Temperature, Nucleic Acid Denaturation, Animals, DNA chemistry
- Abstract
The thermal stabilities of DNA duplexes analogous to the let-7 microRNA: lin-41 mRNA complex from Caenorhabditis elegans have been measured by free solution capillary electrophoresis. DNA duplexes with the same stems but different types of internal or bulge loops and a control with no loop have also been studied. The melting temperatures of the DNA derivatives increased linearly with the logarithm of the Na
+ or K+ ion concentration in the solution. Peaks in the electropherograms corresponding to duplexes with internal or bulge loops exhibited extensive tailing at high temperatures, suggesting that denaturation occurred by slow exchange between the duplexes and their component single strands. The single strands did not separate completely from the duplexes in aqueous solutions; instead, they appeared as small subpeaks on the tails of the duplex peaks. However, complete separation of the duplexes from their component single strands was observed at 20 °C in solutions containing 300 mM tetrapropylammonium ions. In addition, counterion condensation appears to be significantly reduced in DNA duplexes containing internal or bulge loops.- Published
- 2024
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10. How can trial designs better serve the needs of children and young people with juvenile idiopathic arthritis?
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Feilding FL, Crosby L, Earle E, Beesley R, Leslie K, MacDonald E, Wright C, Wilson D, Sherriffs A, Duerr T, and Ramanan AV
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- Humans, Child, Adolescent, Antirheumatic Agents therapeutic use, Arthritis, Juvenile drug therapy, Arthritis, Juvenile therapy, Clinical Trials as Topic ethics, Clinical Trials as Topic methods, Research Design
- Abstract
In juvenile idiopathic arthritis we have seen remarkable progress in the number of available licensed biological and small molecule treatments in the past two decades, leading to improved outcomes for patients. Designing clinical trials for these therapeutics is fraught with ethical, legislative, and practical challenges. However, many aspects of current clinical trial design in juvenile idiopathic arthritis do not meet the needs of patients and clinicians. Commonly used withdrawal trial designs raise substantial ethical concerns for patients and families who believe that they do not enable evidence-based and patient-centred decisions around medication choices. In this Viewpoint, we present the personal views of a patient and parent network that is of the opinion that current trial design in juvenile idiopathic arthritis is failing children and young people with juvenile idiopathic arthritis and set out the need for change informed by lived experience., Competing Interests: Declaration of interests AVR has received consulting fees from Eli Lilly, UCB, AbbVie, Novartis, and Alimera Biosciences. AVR has also received payment or honoraria from Eli Lilly, AbbVie, Pfizer, Novartis, Roche, and Sobi. AVR has participated on a data safety monitoring board or advisory board for Eli Lilly. EE is a trustee for Children's Chronic Arthritis Association (charity number 1185378). All other authors declare no competing interests. Funding for the CLUSTER Project has been provided by generous grants from the Medical Research Council (grant number MR/R013926/1), Versus Arthritis (grant number 22084), Great Ormond Street Hospital Children's Charity (grant number VS0518), and Olivia's Vision. This work is supported by the National Institute for Health and Care Research (NIHR) Great Ormond Street Hospital Biomedical Research Centre, the NIHR Manchester Biomedical Research Centre, the British Society for Rheumatology, and the UK's Experimental Arthritis Treatment Centre for Children, supported by Versus Arthritis (grant number 20621). The CLUSTER consortium has been provided with generous grants from AbbVie and Sobi, and in-kind contributions from GSK, Pfizer, and UCB. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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11. Renal cell carcinoma histologic subtypes exhibit distinct transcriptional profiles.
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Barata P, Gulati S, Elliott A, Hammers HJ, Burgess E, Gartrell BA, Darabi S, Bilen MA, Basu A, Geynisman DM, Dawson NA, Zibelman MR, Zhang T, Wei S, Ryan CJ, Heath EI, Poorman KA, Nabhan C, and McKay RR
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- Humans, Female, Male, Gene Expression Regulation, Neoplastic, Middle Aged, Aged, Neoplasm Proteins genetics, Neoplasm Proteins metabolism, Gene Expression Profiling, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell pathology, Carcinoma, Renal Cell metabolism, Kidney Neoplasms genetics, Kidney Neoplasms pathology, Kidney Neoplasms metabolism, Transcriptome
- Abstract
Molecular profiling of clear cell renal cell carcinoma (ccRCC) tumors of patients in a clinical trial has identified distinct transcriptomic signatures with predictive value, yet data in non-clear cell variants (nccRCC) are lacking. We examined the transcriptional profiles of RCC tumors representing key molecular pathways, from a multi-institutional, real-world patient cohort, including ccRCC and centrally reviewed nccRCC samples. ccRCC had increased angiogenesis signature scores compared with the heterogeneous group of nccRCC tumors, while cell cycle, fatty acid oxidation/AMPK signaling, and fatty acid synthesis/pentose phosphate signature scores were increased in one or more nccRCC subtypes. Among both ccRCC and nccRCC tumors, T effector scores statistically correlated with increased immune cell infiltration and were more commonly associated with immunotherapy-related markers (PD-L1+/TMBhi/MSIhi). In conclusion, this study provides evidence of differential gene transcriptional profiles among ccRCC versus nccRCC tumors, providing insights for optimizing personalized and histology-specific therapeutic strategies for patients with advanced RCC.
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- 2024
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12. Flanking AT base pairs affect the localization of monovalent cations in DNA A-tracts.
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Stellwagen E and Stellwagen NC
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- Base Pairing, Cations, Monovalent chemistry, Base Sequence, Ions, Cations, DNA chemistry
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Capillary electrophoresis has been used to measure the free solution mobilities of a series of 26-base pair (bp) DNA oligomers containing two phased A4T1in-tracts embedded in flanking sequences containing 0 to 11 additional AT bps. A random-sequence 26-bp oligomer with 12 isolated AT bps was used as the reference. Mobility ratios (A-tract/reference) were measured in background electrolytes (BGEs) containing mixtures of small monovalent cations and tetrabutylammonium (TBA
+ ) or tetrapropylammonium (TPA+ ) ions. The mobility ratios observed in 0.3 M TBA+ were >1.00, suggesting that the TBA+ ions had formed electrostatic contact pairs with the AT bp in the reference and in the A-tract flanking sequences, decreasing the mobilities of both oligomers. The TBA-AT pairing interactions could be eliminated by increasing the concentration of small monovalent cations in the BGE. In 0.3 M TPA+ , electrostatic contact pairs were formed with the AT bps in the flanking sequences and in the A-tracts. Interestingly, the shapes of the mobility ratio profiles observed for the A4T1in-tract oligomers depended on the total number of A + T residues in the oligomer., (© 2023 The Authors. Electrophoresis published by Wiley-VCH GmbH.)- Published
- 2024
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13. A case series of sage: a new couple-based intervention for borderline personality disorder.
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Fitzpatrick S, Varma S, Chafe D, Norouzian N, Traynor J, Goss S, Earle E, Di Bartolomeo A, Siegel A, Fulham L, Monson CM, and Liebman RE
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Background: Research suggests that interpersonal dysfunction may be central to borderline personality disorder (BPD), and that the relationships of people with BPD are particularly impaired. Further, the significant others of people with BPD exhibit elevated psychological problems but little access to mental healthcare. Despite this, most BPD interventions are delivered individually and do not routinely incorporate significant others. This manuscript presents the first case series of Sage, a 12-session manualized intervention for people with borderline personality disorder (BPD) and their intimate partners with three targets: a) BPD severity, b) relationship conflict, and c) intimate partner mental health., Findings: Five couples of people with BPD with frequent suicidal/self-injurious behavior or high suicidal ideation and their intimate partners received Sage. Measures of Sage targets as well as tertiary outcomes were administered at pre-, mid-, and post-intervention. Four out of five dyads completed Sage, with high intervention satisfaction ratings. Improvements were generally demonstrated in BPD severity, suicidal ideation, and suicidal behavior/self-injury. Half of dyads exhibited improvements in conflict, and additional improvements in mental health outcomes for dyad members were demonstrated. One dyad exhibited poor outcomes and speculations regarding this are offered., Conclusions: Findings provide proof of concept of Sage as an intervention that can improve BPD and other mental health outcomes in those with BPD and their intimate partners. Incorporating intimate partners into BPD treatment may optimize and expedite its outcomes. However, further testing is needed., Trial Registration: This project was pre-registered at Clinicaltrials.gov (Identifier: [NCT04737252])., (© 2024. The Author(s).)
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- 2024
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14. A Phase 1/2 Study to Evaluate the Safety and Activity of Nivolumab in Combination With Vorolanib, a Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitor, in Patients With Refractory Thoracic Tumors.
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Beckermann KE, Bestvina CM, El Osta B, Sanborn RE, Borghaei H, Lammers PE, Selvaggi G, Whisenant JG, Heimann-Nichols E, Berry L, Hsu CY, Shyr Y, Horn L, and Wakelee H
- Abstract
Introduction: Targeting the tumor microenvironment may enhance response to immunotherapy (immune checkpoint inhibitors) and improve outcomes for patients. This study tested the safety and efficacy of vorolanib, a novel tyrosine kinase inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and c-KIT, in combination with programmed cell death protein 1 blockade using nivolumab for refractory thoracic malignancies., Methods: This single-arm multicenter study enrolled patients with extensive-stage SCLC, thymic carcinoma, and NSCLC, either naive or had progressed on previous chemotherapy or immune checkpoint inhibitors (either primary or acquired resistance). The primary objective of phase 1 was to determine the maximum tolerated dose, and the primary end point for each dose-expansion cohort was the objective response rate., Results: A total of 88 patients were enrolled in phase 1 (n = 11) and dose expansion (n = 77) cohorts. Transaminitis was dose-limiting and expansion proceeded with oral vorolanib 200 mg daily combined with intravenous nivolumab 240 mg every 2 weeks. The objective response rate per cohort were as follows: NSCLC naive 33% (five of 15, 95% confidence interval [CI]: 13%-60%), NSCLC primary refractory 5.9% (one of 17, 95% CI: 0%-17.6%), NSCLC acquired resistance 11.1% (two of 18, 95% CI: 0%-27.8%); SCLC 0% (zero of 18), and thymic carcinoma 11% (one of nine, 95% CI: 0%-33%). Disease control rate ranged from 11.1% in SCLC (two of 18, 0%-27.8%) to 66.7 % in thymic carcinoma (six of nine, 95% CI: 33.3%-100%). The most common adverse events were fatigue (32%), aspartate transaminase (27%) and alanine transaminase elevation (25%), and diarrhea (19%). Transaminitis was more common in patients with thymic carcinoma than other tumors., Conclusions: Vorolanib plus nivolumab had a manageable safety profile and may have clinical benefits in various thoracic malignancies. The disease control rate in thymic malignancies warrants further assessment., Competing Interests: Dr. Beckermann reports receiving institutional funding from Xcovery and Bristol-Myers Squibb for this work and Aravive, Pionyr, and ArsenalBio unrelated to the submitted work; received consulting fees from Aravive, Alpine Bioscience, Aveo, AstraZeneca, Exelixis, Bristol-Myers Squibb, Merck, Sanofi, and Seagen. Dr. Bestvina reports receiving consulting fees from AstraZeneca, Bristol-Myers Squibb, CVS, Daiichi Sankyo, EMD, Serono, Genentech, Gilead, Jazz, JNJ, Mirati, Novartis, Novocure, Pfizer, Regeneron, Sanofi, Takeda, and Tempus; and support for attending meetings from Bristol-Myers Squibb. Dr. Selvaggi is the Chief Medical Officer of Xcovery Holding, Inc. Dr. Sanborn reports receiving consulting fees from GlaxoSmithKline, AstraZeneca, Janssen Oncology, Macrogenics, Daiichi Sankyo, Sanofi Aventis, BeiGene, Gilead, Illumina, Targeted Oncology, Regeneron, G1 Therapeutics, GE HealthCare, Amgen, Abbvie, and Eli Lilly Oncology; and reports receiving payment or honoraria for presentations for EMD-Serono, GameOn!, Illumina, Binay Foundation, OncLive, and Meeting Events and Conference Coordinators, Inc. Dr. Berry reports receiving institutional funding from Xcovery. Dr. Borghaei reports receiving grants from 10.13039/100002491Bristol-Myers Squibb, Eli Lilly, and 10.13039/100002429Amgen; consulting fees from Bristol-Myers Squibb, Eli Lilly, Genentech, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Amgen, Axiom, PharmaMar, Takeda, Mirati, Daiichi, Guardant, Natera, Oncocyte, Beigene, iTEO, Jazz, Janssen, Puma, BerGenBio, Bayer, Iobiotech, and Grid Therapeutics; honoraria from Amgen, Pfizer, Daiichi, and Regeneron; support for attending meetings from Amgen, Bristol-Myers Squibb, Merck, Eli Lilly, EMD-Serono, Genentech, Regeneron, and Mirati; and participated on a Data Safety Monitoring Board or Advisory Board for the University of Pennsylvania CAR T Program, Takeda, Incyte, Novartis, and Springworks. The remaining authors declare no conflict of interest., (© 2023 The Authors.)
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- 2023
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15. Household Food Security and Consumption of Sugar-Sweetened Beverages among New York City (NYC) Children: A Cross-Sectional Analysis of 2017 NYC Kids' Data.
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Flórez KR, Albrecht SS, Hwang N, Chambers E, Li Y, Gany FM, and Davila M
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- Humans, Child, Cross-Sectional Studies, New York City, Carbonated Beverages, Food Security, Beverages analysis, Sugar-Sweetened Beverages adverse effects
- Abstract
Food insecurity is a stressor associated with adverse health outcomes, including the consumption of sugar-sweetened beverages (SSBs). Our study tests the hypothesis that other socioeconomic vulnerabilities may magnify this effect using cross-sectional data from the 2017 New York City (NYC) Kids Survey. Households providing an affirmative response to one or both food security screener questions developed by the US Department of Agriculture were coded as households with low food security. The number of sodas plus other SSBs consumed was standardized per day and categorized as 1 = none, 2 = less than one, and 3 = one or more. We tested the joint effect of low food security with chronic hardship, receipt of federal aid, and immigrant head of household on a sample of n = 2362 kids attending kindergarten and beyond using ordinal logistic regression and accounting for the complex survey design. Only having a US-born parent substantially magnified the effect of low household food security on SSB consumption (OR = 4.2, 95%CI: 2.9-6.3, p < 0.001) compared to the reference group of high household food security with an immigrant parent. The effect of low food security on SSB consumption among NYC children warrants intersectional approaches, especially to elucidate US-based SSB norms in low-food-security settings.
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- 2023
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16. Monovalent cation localization in DNA A-tracts with different sequences.
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Stellwagen E and Stellwagen NC
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- Cations, Monovalent, Base Sequence, Ions, Nucleic Acid Conformation, DNA, Lithium
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The free solution mobilities of 26-base pair (bp) DNA oligomers containing A-tracts with and without internal ApT steps have been measured by capillary electrophoresis, using the mobility of a 26-bp random-sequence oligomer as a reference. The background electrolytes (BGEs) contained mixtures of Li
+ and tetrapropylammonium (TPA+ ) ions, keeping the total cation concentration constant at 0.3 M. The mobility ratios equaled 1.00 in 0.3 M TPA+ , indicating that the A-tract and reference oligomers had the same B-form conformation in this BGE. With increasing [Li+ ], the mobility ratio decreased as Li+ ions became localized in the A-tract minor groove, suggesting that the A-tract was now in the B* conformation. If the A-tract contained an internal ApT step and the oligomer contained less than ∼50% A + T, the mobility ratio reached a reduced plateau value that remained constant as the [Li+ ] increased to 0.3 M. However, for A-tracts without an internal ApT step and for A-tracts embedded in oligomers containing more than 50% A + T, the mobility ratios increased again at high [Li+ ], eventually reaching a plateau value of 1.00. Hence, DNA A-tracts in solution appear to exist as mixtures of the B and B* conformations, with the fractional concentration of each conformer depending on the [Li+ ], the A-tract sequence, and the total A + T content of the oligomer., (© 2023 The Authors. Electrophoresis published by Wiley-VCH GmbH.)- Published
- 2023
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17. Arthroscopic knots: Suture and knot characterisation of modern polyblend suture materials.
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Savage E, Hurren CJ, Rajmohan GD, Thomas W, and Page RS
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Objective: The primary aim of this study was to explore the relationship between the biophysical structure and function of modern suture materials. Particularly the suture's ability to withstand the stressors of surgery and how the material properties affect knot stability. The secondary aim was to investigate the effect that different knots have on the suture material itself. This study builds on previous research assessing suture and knot characteristics but in modern Ultra High Molecular Weight Polyethylene (UHMWPE) materials currently in widespread clinical use in arthroscopic surgery., Methods: Three common UHMWPE sutures and one polyester suture were tested in both a dry and wet state using the Geelong, Nicky's, Surgeon's and Tautline knots. Tensile strength of knots was tested vertically at a 60 mm/min strain rate and 45 mm gauge length. Sutures were tied through a cannula around two 8 mm diameter circular bollards. Testing was conducted in a controlled environment temperature and humidity environment (20 ± 2 °C, 65 ± 2%)., Results: No one knot type was optimal over all suture types. Mean tensile strength in both a dry and wet state and a low coefficient of variation (CV) in tensile strength in a wet state were considered as an indication of suitability. With Ethibond sutures this was the Geelong knot (CV:4.2%). With Orthocord sutures both the Geelong and Tautline knots (CV:4.2% and CV:11.9% respectively). With FiberWire sutures the Nickys and Tautline knots (CV:22.6% and CV:22.5% respectively). With ForceFiber sutures all four knots exhibited similar wet tensile strength with high variability showing that all should perform in a similar way invivo ., Conclusions: This study demonstrates a statistically significant three-way interaction between polyblend suture materials, the knot and the environment. This has implications for knot security using the tested sutures in different environments, as one knot may not behave the same under all conditions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)
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- 2023
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18. Partner outcomes from an uncontrolled trial of Couple HOPES: A guided online couple intervention for posttraumatic stress disorder and relationship enhancement.
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Crenshaw AO, Whitfield KM, Collins A, Valela R, Varma S, Landy MSH, Ip J, Donkin V, Earle E, Siegel A, Samonas C, Bushe J, Mensah DH, Xiang A, Doss BD, Morland L, Wagner AC, Fitzpatrick S, and Monson CM
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- Humans, Interpersonal Relations, Quality of Life, Treatment Outcome, Stress Disorders, Post-Traumatic psychology, Couples Therapy methods
- Abstract
Posttraumatic stress disorder (PTSD) is associated with significant individual and relationship impairment for people with PTSD and their romantic partners. Conjoint treatments, such as cognitive behavioral conjoint therapy for PTSD (CBCT), are designed to address individual and relationship factors, yet significant barriers impede accessing in-person therapy. Couple HOPES (i.e., Helping Overcome PTSD and Enhance Satisfaction) is a coach-guided, online couple intervention for PTSD based on CBCT that was designed to address these barriers. Previous investigations have found preliminary efficacy of Couple HOPES for improving PTSD symptoms, relationship functioning, and some individual functioning domains for the partner with probable PTSD. However, no study to date has tested individual outcomes for romantic partners, which is needed to fully evaluate the intervention's promise. The current study tested these partner outcomes in a combined, uncontrolled sample of 27 couples. Intent-to-intervene analyses found significant improvements at postintervention in four of eight tested outcomes, including ineffective arguing, g = 0.74; anger, g = 0.32; perceived health, g = 0.67; and quality of life, g = 0.56. Depressive symptoms, generalized anxiety, alcohol misuse, and work functioning did not significantly change, gs = 0.17-0.42. Among participants who completed a 1-month follow-up assessment, generalized anxiety, g = 0.43, and perceived health, g = 0.73, significantly improved over follow-up, whereas anger, g = -0.48, lost gains previously made. Results were largely consistent in the completer sample. These findings show the potential of Couple HOPES to have broad benefits not only for individuals with probable PTSD but also for their romantic partners., (© 2022 International Society for Traumatic Stress Studies.)
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- 2023
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19. EphrinB2 Inhibition and Pembrolizumab in Metastatic Urothelial Carcinoma.
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Sadeghi S, Quinn D, Dorff T, Pal S, Groshen S, Tsao-Wei D, Parikh R, Devitt M, Parikh M, Jackovich A, Ruel N, Vogelzang N, Burgess E, Siddiqi I, Gill IS, Lara PN, Dreicer R, and Gill PS
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- Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neoplasm Recurrence, Local drug therapy, Carcinoma, Transitional Cell drug therapy, Ephrin-B2 antagonists & inhibitors, Urinary Bladder Neoplasms drug therapy, Antibodies, Monoclonal, Humanized therapeutic use
- Abstract
Purpose: Patients with metastatic urothelial carcinoma have poor prognosis after failure of standard first-line chemotherapy. Immune check point programmed death 1-programmed death ligand 1 antibodies have low response rates and thus there exists a major unmet need., Materials and Methods: In this phase II trial, patients with metastatic urothelial carcinoma that recurred or progressed after platinum-based chemotherapy received soluble EphB4-human serum albumin (sEphB4-HSA) in combination with pembrolizumab. The primary end points were tolerability and overall survival (OS). The secondary end points were progression-free survival (PFS), objective response rate (ORR), duration of response, and toxicity. The expression of sEphB4-HSA target EphrinB2 was correlated with outcomes., Results: Seventy patients were enrolled. The median follow up was 22.9 months (range, 1.3-54.7). The regimen had acceptable toxicity. In the intent-to-treat analysis (N = 70), the median OS was 14.6 months (95% CI, 9.2 to 21.5). Twenty-six (37%) patients had an objective response (95% CI, 26 to 48). The median PFS was 4.1 (95% CI, 1.5 to 5.7) months. Forty-six (66%) patients expressed EphrinB2, and among them, the median OS was 21.5 months (95% CI, 12.4 to not reached), the ORR was 52% (95% CI, 37 to 67), including a complete response rate of 24% (11 of 46; 95% CI, 12 to 36). The median PFS was 5.7 (95% CI, 2.7 to 27.9) months. Response was maintained at 6, 12, and 24 months in 88%, 74%, and 69% of the patients, respectively., Conclusion: The combination of sEphB4-HSA and pembrolizumab appears synergistic with improved OS and ORR compared with historical data for programmed death 1/programmed death ligand 1 monotherapy.
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- 2023
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20. Community Choir Improves Vocal Production Measures in Individuals Living with Parkinson's Disease.
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Good A, Earle E, Vezer E, Gilmore S, Livingstone S, and Russo FA
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Objectives: Parkinson's disease (PD) is a neurodegenerative disease leading to motor impairments and dystonia across diverse muscle groups including vocal muscles. The vocal production challenges associated with PD have received considerably less research attention than the primary gross motor symptoms of the disease despite having a substantial effect on quality of life. Increasingly, people living with PD are discovering group singing as an asset-based approach to community building that is purported to strengthen vocal muscles and improve vocal quality., Study Design/methods: The present study investigated the impact of community choir on vocal production in people living with PD across two sites. Prior to and immediately following a 12-week community choir at each site, vocal testing included a range of vocal-acoustic measures, including lowest and highest achievable pitch, duration of phonation, loudness, jitter, and shimmer., Results: Results showed that group singing significantly improved some, though not all, measures of vocal production. Group singing improved lowest pitch (both groups), duration (both groups), intensity (one group), and jitter (one group) and shimmer (both groups)., Conclusions: These findings support community choir as a feasible and scalable complementary approach to managing vocal production challenges associated with PD., (Copyright © 2023. Published by Elsevier Inc.)
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- 2023
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21. Chemical data evaluation: general considerations and approaches for IUPAC projects and the chemistry community (IUPAC Technical Report).
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Shaw DG, Bruno I, Chalk S, Hefter G, Hibbert DB, Hutchinson RA, Magalhães MCF, Magee J, McEwen LR, Rumble J, Russell GT, Waghorne E, Walczyk T, and Wallington TJ
- Abstract
The International Union of Pure and Applied Chemistry (IUPAC) has a long tradition of supporting the compilation of chemical data and their evaluation through direct projects, nomenclature and terminology work, and partnerships with international scientific bodies, government agencies and other organizations. The IUPAC Interdivisional Subcommittee on Critical Evaluation of Data (ISCED) has been established to provide guidance on issues related to the evaluation of chemical data. In this first report we define the general principles of the evaluation of scientific data and describe best practices and approaches to data evaluation in chemistry.
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- 2023
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22. Social Needs Assessment and Linkage to Community Health Workers in a Large Urban Hospital System.
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Shi M, Fiori K, Kim RS, Gao Q, Umanski G, Thomas I, Telzak A, and Chambers E
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- Humans, Female, Adolescent, Young Adult, Adult, Middle Aged, Aged, Needs Assessment, Cross-Sectional Studies, Hospitals, Urban, Community Health Workers, Delivery of Health Care
- Abstract
Objectives: Identifying social needs is a growing priority in primary care, but there is significant variation in how patients access services to meet such needs. This study identifies predictors of successful linkage with a community health worker (CHW) among patients with social needs seen in an outpatient setting., Methods: This study uses a cross-sectional analysis of social needs assessments administered in an urban health system between April 2018 and December 2019. Social needs included: food insecurity, housing quality, housing instability, healthcare cost, healthcare related transportation, utilities, care for dependents, legal assistance, safety, and getting along with household members. Patients with at least 1 social need and accepting help were included in the analysis. On contact with a CHW, patients were entered into a separate database. The primary outcome was successful "linkage," defined by having a positive social needs assessment in the medical record and a corresponding record in the CHW database. Multivariate logistic regression was used to assess predictors of linkage., Results: Among patients with at least 1 social need accepting help, 25% (758/3064) were linked to a CHW. Positive predictors included female gender (OR 1.28 [95% CI 1.01-1.63]), Spanish language preference compared to English (1.51 [1.14-1.03]), and having a food related need (1.35 [1.03-1.79]). Negative predictors included age 18 to 65 (0.34 [0.17-0.71] for age 18-24) and 0 to 5 (0.45 [0.24-0.78]) compared to over 65, non-Hispanic White race compared to Hispanic race (0.39 [0.18-0.84]), and having needs of getting along with household members (0.52 [0.38-0.71]) and safety (0.64 [0.42-0.98])., Conclusions: Twenty-five percent of patients who had at least 1 social need and were accepting help had a successful CHW linkage. Predictors of linkage suggest areas of further system-level improvements to screening and referral interventions to target at risk patients and communities.
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- 2023
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23. A Phase 3b Study for Management of Ocular Side Effects in Patients with Epidermal Growth Factor Receptor-Amplified Glioblastoma Receiving Depatuxizumab Mafodotin.
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Vize CJ, Kim SK, Matthews T, Macsai M, Merrell R, Hsu S, Kundu MG, Yoon J, Kennedy E, Pai M, Bain E, Lassman AB, and Moazami G
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- Adult, Humans, ErbB Receptors metabolism, Ophthalmic Solutions therapeutic use, Steroids therapeutic use, Temozolomide therapeutic use, Vasoconstrictor Agents therapeutic use, Glioblastoma drug therapy, Glioblastoma metabolism, Glioblastoma pathology
- Abstract
Introduction: The Understanding New Interventions with GBM ThErapy (UNITE) study was designed to assess the effect of prophylaxis for ocular side effects (OSEs) in patients with glioblastoma receiving the antibody-drug conjugate (ADC) depatuxizumab mafodotin. UNITE (NCT03419403) was a phase 3b, open-label, randomized, exploratory study performed at 18 research sites in 5 countries., Methods: The study enrolled adult patients with epidermal growth factor receptor-amplified, histologically confirmed, newly diagnosed supratentorial glioblastoma or grade IV gliosarcoma, and a Karnofsky Performance Status ≥70, receiving depatuxizumab mafodotin. All patients were administered depatuxizumab mafodotin during concurrent radiotherapy and temozolomide and with adjuvant temozolomide. Ninety patients were to be randomized (1:1:1) to OSE prophylactic treatments with each depatuxizumab mafodotin infusion: (a) standard steroid eye drops, (b) standard steroid eye drops plus vasoconstrictor eye drops and cold compress, or (c) enhanced steroids plus vasoconstrictor eye drops and cold compress. A Corneal Epitheliopathy Adverse Event (CEAE) scale was devised to capture symptoms, grade OSEs (scale of 0-5), and inform ADC dose modifications. The primary endpoint was the frequency of a required change in OSE management due to inadequate control of OSEs, defined as decline from baseline in visual acuity (using logarithm of the minimum angle of resolution [LogMAR] scale) or a Grade ≥3 CEAE event, in the worst eye in the first 8 weeks of treatment; unless otherwise specified, the treatment period refers to both the chemoradiation and adjuvant phases., Results: The UNITE study was stopped early after interim analysis of separate phase III trial showed no difference in survival from depatuxizumab mafodotin. Forty patients were randomized (38 received depatuxizumab mafodotin). Overall, 23 patients experienced inadequate control of OSEs that required change in OSE management within 8 weeks of treatment, with 21 (70.0%) experiencing ≥+0.3 change on LogMAR scale in baseline-adjusted visual acuity and 12 reporting a grade ≥3 CEAE. There were no definitive differences among prophylactic treatments., Conclusions: The premature cessation of the study precludes definitive conclusions regarding the OSE prophylaxis strategies. No new clinically significant safety findings were noted. Despite these limitations, this study highlights the need for novel assessment tools to better understand and mitigate OSEs associated with ADCs., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
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- 2023
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24. An assessment of burnout in New Zealand orthopaedic resident medical officers.
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Martyn TLB, Savage E, and MacLean SBM
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- Humans, New Zealand epidemiology, Burnout, Psychological, Health Personnel, Orthopedics, COVID-19 epidemiology
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Aims: Burnout and fatigue are common in the medical profession. The primary aim was to assess rates of burnout in trainee and non-trainee orthopaedic registrars in New Zealand. A secondary aim was to establish which specific factors are associated with burnout., Methods: In 2021, a 53-question online survey was sent to New Zealand trainee and non-trainee orthopaedic registrars. The survey included questions addressing demographics, modifiable factors known to lead to burnout, information on respective orthopaedic departments, and how respondents had fared with COVID-19. Registrars also completed the Maslach Burnout Inventory-Human Services Survey for Medical Personnel (MBI-HSS MP), a 22-question validated survey that is designed to assess the frequency and intensity of perceived burnout among medical personnel., Results: Fifty of 62 (80.6%) trainees and 66 of 70 (estimated number) (94.3%) of non-trainees completed the survey. Trainees and non-trainees both exhibited moderate levels of burnout. The trainee mean score emotional exhaustion (EE) 22.5, depersonalisation (DP) 8.8, personal achievement (PA) 35.9; non-trainee mean score EE 22.4, DP 8.9, PA 35.9. Fifty-two point two percent of trainees and 50% of non-trainees scored in the severe range for at least one of EE or DP. Factors shown to reduce burnout are the presence of a senior colleague (P<0.001), participation in professional assistance (P=0.049), working in a department with a full complement of staff (P=0.020) and being able to attend health maintenance appointments (P=0.050)., Conclusion: Our study shows that approximately half of both trainee and non-trainee orthopaedic registrars are exhibiting signs of burnout. This is comparable to other developed nations with a similar healthcare system., Competing Interests: Nil., (© PMA.)
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- 2022
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25. Life cycle assessment of microalgal biorefinery: A state-of-the-art review.
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Ubando AT, Anderson S Ng E, Chen WH, Culaba AB, and Kwon EE
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- Animals, Biofuels, Biomass, Biotechnology, Life Cycle Stages, Microalgae
- Abstract
Microalgal biorefineries represent an opportunity to economically and environmentally justify the production of bioproducts. The generation of bioproducts within a biorefinery system must quantitatively demonstrate its viability in displacing traditional fossil-based refineries. To this end, several works have conducted life cycle analyses on microalgal biorefineries and have shown technological bottlenecks due to energy-intensive processes. This state-of-the-art review covers different studies that examined microalgal biorefineries through life cycle assessments and has identified strategic technologies for the sustainable production of microalgal biofuels through biorefineries. Different metrics were introduced to supplement life cycle assessment studies for the sustainable production of microalgal biofuel. Challenges in the comparison of various life cycle assessment studies were identified, and the future design choices for microalgal biorefineries were established., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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26. Que devraient enseigner les éducateurs pour améliorer les soins de santé préventifs?
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Grad R, Antao V, Bell NR, Dickinson JA, Rezkallah R, Singh H, Szafran O, Waugh E, and Thériault G
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- 2022
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27. What should educators teach to improve preventive health care?
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Grad R, Antao V, Bell NR, Dickinson JA, Rezkallah R, Singh H, Szafran O, Waugh E, and Thériault G
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- Humans, Curriculum, Preventive Health Services
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- 2022
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28. Going against the status quo in screening: Call to action to improve teaching in preventive health care.
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Antao V, Grad R, Thériault G, Dickinson JA, Szafran O, Singh H, Rezkallah R, Waugh E, and Bell NR
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- Humans, Research, Surveys and Questionnaires, Mass Screening, Preventive Health Services
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- 2022
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29. À l’encontre du statu quo en matière de dépistage: Appel à l’action pour améliorer l’enseignement des soins de santé préventifs.
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Antao V, Grad R, Thériault G, Dickinson JA, Szafran O, Singh H, Rezkallah R, Waugh E, and Bell NR
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- 2022
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30. One Hundred Percent Reparability of Mitral Prolapse: Results of a Dynamic Nonresectional Technique.
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Lawrie G, Zoghbi W, Little S, Shah D, Earle N, and Earle E
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- Female, Heart Valve Prosthesis, Humans, Male, Middle Aged, Prosthesis Design, Recurrence, Retrospective Studies, Treatment Outcome, Mitral Valve surgery, Mitral Valve Annuloplasty methods, Mitral Valve Prolapse surgery
- Abstract
Background: We studied the results of a dynamic mitral repair technique that preserves normal mitral valve function by avoiding leaflet resection and rigid and semirigid annuloplasty rings., Methods: In previous reports we demonstrated that intraoperative simulation of mitral valve locking and isovolumic systole by rapid left ventricular inflation with pressurized saline accurately simulates mitral annular and leaflet shape and position, and left ventricular outflow tract dimensions. Length of polytetrafluoroethylene neochordae and size of fully flexible adjustable annuloplasty ring can be adjusted in three dimensions for accurate apposition of zones of leaflet coaptation, premarked with dots. We followed 1068 consecutive patients after repairs performed between 2001 and 2018., Results: Of the 1068 patients, 674 were men (63.1%). Mean age was 62.25 ± 13 years. Leaflet repaired was anterior in 118 patients (11.05%), posterior in 564 (52.81%), both in 55 (5.15%), and neither in 123 (11.5%). Barlow's disease was present in 208 patients (19.48%). Repair was isolated in 82.5% (881 of 1068). Reparability was 100%. Perioperative mortality overall was 1.59% (17 of 1068): isolated repair, 1.14% (10 of 881); and isolated posterior leaflet, 0.85% (4 of 472). Leaflet systolic anterior motion occurred in 1.7% (18 of 1068), and was significant in 0.4% (4 of 1068). Survival at 10 years by Kaplan-Meier analysis was 74.65%, freedom from reoperation was 96.01%, and freedom from severe mitral regurgitation was 94%. The only predictor of reoperation (Cox analysis) was being male (P = .001)., Conclusions: Use of intraoperative simulation of mitral dynamics led to 100% reparability for degenerative valves with minimal systolic anterior motion, despite no leaflet resection. Long-term durability has been good and similar for all leaflets., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
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