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Article ; Online: Effect of reciprocity-breaking on fine-track tip/tilt systems.

Isaacs, J / Parks, D / DiComo, G / Helle, M

Applied optics

2023 Volume 62, Issue 17, Page(s) 4699–4705

Abstract: We analyze here a candidate system for correcting the wander of a self-channeled laser pulse using a fast-steering mirror along with a cooperative beacon imaged with a telescope. For our model system, the imaging telescope is coaxial with the propagation ...

Abstract	We analyze here a candidate system for correcting the wander of a self-channeled laser pulse using a fast-steering mirror along with a cooperative beacon imaged with a telescope. For our model system, the imaging telescope is coaxial with the propagation of the outgoing pulse. In the ideal case, any incoming light gathered from the beacon would be collimated, such that taking a centroid beacon image would yield the precise tip and tilt required for the self-channeled pulse to propagate back to the beacon on the reciprocal path. The degree to which reality differs from this ideal case determines the effectiveness of the wander correction. We simulate our system for a range of propagation and imaging conditions. We also show that in the absence of image noise (i.e., when the beacon power is arbitrarily high, and the signal-to-noise ratio is not an important consideration), the system exhibits its best performance when the receiving aperture diameter of the imaging system is close to the transverse size of the outgoing pulse, maximizing reciprocity. When realistic noise and finite beacon power are included in the simulation, however, we find that this reciprocity advantage may not be sufficient to compensate for the reduced photon count and resolving power of a small receiving aperture. In this case, the optimal aperture diameter will be the smallest possible, which allows for an acceptable signal-to-noise ratio.
Language	English
Publishing date	2023-09-14
Publishing country	United States
Document type	Journal Article
ISSN	1539-4522
ISSN (online)	1539-4522
DOI	10.1364/AO.491531
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Article ; Online: Erratum for Lickliter et al., "Safety, Pharmacokinetics, and Drug-Drug Interaction Potential of Intravenous Durlobactam, a β-Lactamase Inhibitor, in Healthy Subjects".

Lickliter, Jason D / Lawrence, Kenneth / O'Donnell, John / Isaacs, Robin

Antimicrobial agents and chemotherapy

2023 Volume 67, Issue 6, Page(s) e0047623

Language	English
Publishing date	2023-05-08
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/aac.00476-23
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Article ; Online: Targeted editing and evolution of engineered ribosomes in vivo by filtered editing.

Radford, Felix / Elliott, Shane D / Schepartz, Alanna / Isaacs, Farren J

Nature communications

2022 Volume 13, Issue 1, Page(s) 180

Abstract: Genome editing technologies introduce targeted chromosomal modifications in organisms yet are constrained by the inability to selectively modify repetitive genetic elements. Here we describe filtered editing, a genome editing method that embeds group 1 ... ...

Abstract	Genome editing technologies introduce targeted chromosomal modifications in organisms yet are constrained by the inability to selectively modify repetitive genetic elements. Here we describe filtered editing, a genome editing method that embeds group 1 self-splicing introns into repetitive genetic elements to construct unique genetic addresses that can be selectively modified. We introduce intron-containing ribosomes into the E. coli genome and perform targeted modifications of these ribosomes using CRISPR/Cas9 and multiplex automated genome engineering. Self-splicing of introns post-transcription yields scarless RNA molecules, generating a complex library of targeted combinatorial variants. We use filtered editing to co-evolve the 16S rRNA to tune the ribosome's translational efficiency and the 23S rRNA to isolate antibiotic-resistant ribosome variants without interfering with native translation. This work sets the stage to engineer mutant ribosomes that polymerize abiological monomers with diverse chemistries and expands the scope of genome engineering for precise editing and evolution of repetitive DNA sequences.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; CRISPR-Cas Systems ; Escherichia coli/drug effects ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Exons ; Gene Editing/methods ; Genetic Engineering ; Genome, Bacterial ; Introns ; Mutagenesis, Site-Directed/methods ; Polymers/chemistry ; Protein Biosynthesis ; RNA Splicing ; RNA, Ribosomal, 16S/genetics ; RNA, Ribosomal, 16S/metabolism ; RNA, Ribosomal, 23S/genetics ; RNA, Ribosomal, 23S/metabolism ; Repetitive Sequences, Nucleic Acid ; Ribosomes/genetics ; Ribosomes/metabolism
Chemical Substances	Anti-Bacterial Agents ; Polymers ; RNA, Ribosomal, 16S ; RNA, Ribosomal, 23S
Language	English
Publishing date	2022-01-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-27836-x
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Article ; Online: The role of comorbidities alongside patient and disease characteristics in long-term disease activity in RA using UK inception cohort data.

Busby, Amanda D / Wason, James / Pratt, Arthur G / Young, Adam / Isaacs, John D / Nikiphorou, Elena

Rheumatology (Oxford, England)

2023 Volume 61, Issue 11, Page(s) 4297–4304

Abstract: Objectives: Control of disease activity in RA is a crucial part of its management to prevent long-term joint damage and disability. This study aimed to identify early predictors of poor disease activity at 5 and 10 years, focusing on comorbidities and ... ...

Abstract	Objectives: Control of disease activity in RA is a crucial part of its management to prevent long-term joint damage and disability. This study aimed to identify early predictors of poor disease activity at 5 and 10 years, focusing on comorbidities and clinical/sociodemographic factors at first presentation. Methods: Patients from two UK-based RA cohorts were classified into two groups; low (<3.2) and moderate/high (≥3.2) DAS using 28 joint counts (DAS28) at 5/10 years. Clinical variables (e.g. rheumatoid nodules, erosions), sociodemographic factors (e.g. ethnicity, deprivation) and comorbidities were recorded at baseline and yearly thereafter. The Rheumatic Diseases Comorbidity Index quantified patient comorbidity burden. Binary logistic regression models (outcome low vs moderate/high DAS28) were fitted using multiple imputation. Results: A total of 2701 patients living with RA were recruited (mean age 56.1 years, 66.9% female); 5-year data were available for 1718 (63.4%) patients and 10-year data for 820 (30.4%). Baseline Rheumatic Diseases Comorbidity Index was not associated with DAS28 at 5 [odds ratio (OR) 1.05, 95% CI 0.91, 1.22] or 10 years (OR 0.99, 95% CI 0.75, 1.31) in multivariable analyses. Sociodemographic factors (female gender, worse deprivation) and poorer baseline HAQ-Disability Index were associated with DAS28 ≥3.2 at both timepoints. Being seropositive was associated with 5-year DAS28 ≥3.2. Conclusion: This study demonstrates an association between sociodemographic and clinical factors and long-term RA disease activity, in models adjusting for comorbidity burden. The findings call for more holistic and targeted patient management in patients with RA and provide insights for more individualized management plans even on first presentation to rheumatology.
MeSH term(s)	Humans ; Female ; Middle Aged ; Male ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/drug therapy ; Comorbidity ; Disabled Persons ; United Kingdom
Chemical Substances	Antirheumatic Agents
Language	English
Publishing date	2023-03-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keac139
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Article ; Online: The impact of climate change and biodiversity loss on the health of children: An ethical perspective.

Williams, Phoebe C M / Beardsley, Justin / Isaacs, David / Preisz, Anne / Marais, Ben J

Frontiers in public health

2023 Volume 10, Page(s) 1048317

Abstract: The reality of human induced climate change is no longer in doubt, but the concerted global action required to address this existential crisis remains inexcusably inert. Together with climate change, biodiversity collapse is increasingly driving the ... ...

Abstract	The reality of human induced climate change is no longer in doubt, but the concerted global action required to address this existential crisis remains inexcusably inert. Together with climate change, biodiversity collapse is increasingly driving the emergence and spread of infectious diseases, the consequences of which are inequitable globally. Climate change is regressive in its nature, with those least responsible for destroying planetary health at greatest risk of suffering the direct and indirect health consequences. Over half a billion of the world's children live in areas vulnerable to extreme weather events. Without immediate action, the health of today's children and future generations will be compromised. We consider the impact of biodiversity collapse on the spread of infectious diseases and outline a duty of care along a continuum of three dimensions of medical ethics. From a medical perspective, the first dimension requires doctors to serve the best interests of their individual patients. The second dimension considers the public health dimension with a focus on disease control and cost-effectiveness. The neglected third dimension considers our mutual obligation to the future health and wellbeing of children and generations to come. Given the adverse impact of our ecological footprint on current and future human health, we have a collective moral obligation to act.
MeSH term(s)	Humans ; Child ; Climate Change ; Biodiversity ; Communicable Diseases ; Public Health
Language	English
Publishing date	2023-01-20
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2022.1048317
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Article ; Online: A scoping review of web-based, interactive, personalized decision-making tools available to support breast cancer treatment and survivorship care.

Wojcik, Kaitlyn M / Kamil, Dalya / Zhang, Julia / Wilson, Oliver W A / Smith, Laney / Butera, Gisela / Isaacs, Claudine / Kurian, Allison / Jayasekera, Jinani

Journal of cancer survivorship : research and practice

2024

Abstract: Purpose: We reviewed existing personalized, web-based, interactive decision-making tools available to guide breast cancer treatment and survivorship care decisions in clinical settings.: Methods: The study was conducted using the Preferred Reporting ... ...

Abstract	Purpose: We reviewed existing personalized, web-based, interactive decision-making tools available to guide breast cancer treatment and survivorship care decisions in clinical settings. Methods: The study was conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). We searched PubMed and related databases for interactive web-based decision-making tools developed to support breast cancer treatment and survivorship care from 2013 to 2023. Information on each tool's purpose, target population, data sources, individual and contextual characteristics, outcomes, validation, and usability testing were extracted. We completed a quality assessment for each tool using the International Patient Decision Aid Standard (IPDAS) instrument. Results: We found 54 tools providing personalized breast cancer outcomes (e.g., recurrence) and treatment recommendations (e.g., chemotherapy) based on individual clinical (e.g., stage), genomic (e.g., 21-gene-recurrence score), behavioral (e.g., smoking), and contextual (e.g., insurance) characteristics. Forty-five tools were validated, and nine had undergone usability testing. However, validation and usability testing included mostly White, educated, and/or insured individuals. The average quality assessment score of the tools was 16 (range: 6-46; potential maximum: 63). Conclusions: There was wide variation in the characteristics, quality, validity, and usability of the tools. Future studies should consider diverse populations for tool development and testing. Implications for cancer survivors: There are tools available to support personalized breast cancer treatment and survivorship care decisions in clinical settings. It is important for both cancer survivors and physicians to carefully consider the quality, validity, and usability of these tools before using them to guide care decisions.
Language	English
Publishing date	2024-03-28
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2388888-X
ISSN	1932-2267 ; 1932-2259
ISSN (online)	1932-2267
ISSN	1932-2259
DOI	10.1007/s11764-024-01567-6
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Article ; Online: Significant publications in diabetes pharmacotherapy and technology in 2020.

Clements, Jennifer N / Franks, Rachel / Isaacs, Diana / Malloy, Kevin / Meade, Lisa T / Reece, Sara Mandy / Reid, Debra J / Ward, Eileen D

Expert review of endocrinology & metabolism

2023 Volume 18, Issue 2, Page(s) 131–142

Abstract: Introduction: The most significant articles on diabetes pharmacotherapy and technology in the peer-reviewed literature from 2020, as determined by a panel of pharmacists with expertise in diabetes care and education, are summarized.: Areas covered: ... ...

Abstract	Introduction: The most significant articles on diabetes pharmacotherapy and technology in the peer-reviewed literature from 2020, as determined by a panel of pharmacists with expertise in diabetes care and education, are summarized. Areas covered: Members of the Association of Diabetes Care and Education Specialists Pharmacy Community of Interest were selected to review articles published in prominent peer-reviewed journals in 2020 that most impacted diabetes pharmacotherapy and technology. A list of 37 nominated articles were compiled (22 in diabetes pharmacotherapy and 15 in diabetes technology). Based on discussion among the authors, the articles were ranked based on significant contribution, impact, and diversity to diabetes pharmacotherapy and technology. The top 10 highest ranked publications (n = 6 for diabetes pharmacotherapy and n = 4 in diabetes technology) are summarized in this article. Expert opinion: With the significant number of publications in diabetes care and education, it can be challenging and overwhelming to remain current with published literature. This review article may be helpful in identifying key articles in diabetes pharmacotherapy and technology from the year 2020.
MeSH term(s)	Humans ; Communicable Diseases/drug therapy ; Anti-Infective Agents/therapeutic use ; Peer Review ; Diabetes Mellitus/drug therapy
Chemical Substances	Anti-Infective Agents
Language	English
Publishing date	2023-03-07
Publishing country	England
Document type	Review ; Journal Article
ISSN	1744-8417
ISSN (online)	1744-8417
DOI	10.1080/17446651.2023.2187779
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Article ; Online: Clinical Predictors of Device-Detected Atrial Fibrillation During 2.5 Years After Cardiac Surgery: Prospective RACE V Cohort.

Gilbers, Martijn D / Kawczynski, Michal J / Bidar, Elham / Maesen, Bart / Isaacs, Aaron / Winters, Joris / Linz, Dominik / Rienstra, Michiel / van Gelder, Isabelle / Maessen, Jos G / Schotten, Ulrich

JACC. Clinical electrophysiology

2024

Abstract: Background: Postoperative atrial fibrillation (POAF) is a frequent complication after cardiac surgery that is associated with late atrial fibrillation (AF) recurrences (late-POAF) and increased morbidity and long-term mortality.: Objectives: This ... ...

Abstract	Background: Postoperative atrial fibrillation (POAF) is a frequent complication after cardiac surgery that is associated with late atrial fibrillation (AF) recurrences (late-POAF) and increased morbidity and long-term mortality. Objectives: This study sought to determine device-detected POAF incidence and to identify clinical variables associated with POAF, both in patients with and without preoperative AF history. Methods: A total of 133 consecutive patients undergoing cardiac surgery were prospectively enrolled and continuously monitored with an implantable loop recorder for 2.5 years after surgery. Preoperative transthoracic echocardiography, 12-lead electrocardiogram, blood biomarkers, and clinical data were analyzed to develop prediction models for early- and late-POAF. Results: In patients without preoperative AF history, early-POAF within the first 90 postoperative days occurred in 41 (47.1%) of 87 patients. Late-POAF after the first 90 postoperative days occurred in 22 (25%) of 87 patients, and 20 of these patients also had early-POAF during the first 90 days (20 of 22 [91%]). Increased right atrial minimum volume indexed for body surface area (RAVI Conclusions: In patients with and without AF history, late-POAF recurrences are frequent, including in patients undergoing surgical AF ablation. In patients with no history of AF, late-POAF might be predicted with excellent accuracy by using a combination of preoperative variables. In patients with a history of AF, signs of advanced AF substrate (eg, increased right atrial volumes) were associated with long-term AF recurrences. [Reappraisal of Atrial Fibrillation: Interaction Between Hypercoagulability, Electrical Remodeling, and Vascular Destabilisation in the Progression of AF; NCT03124576].
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2846739-5
ISSN	2405-5018 ; 2405-500X ; 2405-500X
ISSN (online)	2405-5018 ; 2405-500X
ISSN	2405-500X
DOI	10.1016/j.jacep.2024.01.013
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Article ; Online: Has COVID-19 affected dementia diagnosis rates in England?

Hazan, Jemma / Liu, Kathy Y / Isaacs, Jeremy D / Burns, Alistair / Howard, Robert

International journal of geriatric psychiatry

2023 Volume 38, Issue 7, Page(s) e5976

Abstract: Background: The COVID-19 pandemic impacted on the provision of care and routine activity of all National Health Service (NHS) services. While General Practitioner referrals to memory services in England have returned to pre-pandemic levels, the ... ...

Abstract	Background: The COVID-19 pandemic impacted on the provision of care and routine activity of all National Health Service (NHS) services. While General Practitioner referrals to memory services in England have returned to pre-pandemic levels, the estimated dementia diagnosis rate (DDR) fell by 5.4% between March 2020 and February 2023. Methods: In this paper we explore whether this reduction is accurate or is an artefact of the way the NHS collects data. Results: We explore the processes that may have affected national dementia diagnosis rates during and following the COVID-19 pandemic. Conclusions: We discuss what action could be taken to improve the DDR in the future.
MeSH term(s)	Humans ; COVID-19/diagnosis ; COVID-19/epidemiology ; State Medicine ; Pandemics ; England/epidemiology ; Dementia/diagnosis ; Dementia/epidemiology ; COVID-19 Testing
Language	English
Publishing date	2023-07-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	806736-3
ISSN	1099-1166 ; 0885-6230
ISSN (online)	1099-1166
ISSN	0885-6230
DOI	10.1002/gps.5976
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Article: A Review of Incretin Therapies Approved and in Late-Stage Development for Overweight and Obesity Management.

Chetty, Ashwin Kanna / Rafi, Ebne / Bellini, Natalie J / Buchholz, Natalie / Isaacs, Diana

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

2023 Volume 30, Issue 3, Page(s) 292–303

Abstract: Objective: To review clinical trial data for incretin therapies that are approved or in late-stage development for overweight or obesity management, along with clinical implications of these therapies and future directions.: Methods: We searched for ... ...

Abstract	Objective: To review clinical trial data for incretin therapies that are approved or in late-stage development for overweight or obesity management, along with clinical implications of these therapies and future directions. Methods: We searched for clinical trials involving incretin therapies studied specifically for overweight or obesity management in ClinicalTrials.gov and PubMed from registry inception through December 2023. Results: Glucagon-like peptide-1 (GLP-1) receptor agonism, alone and in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonism or glucagon agonism, leads to significant weight reduction in people with overweight or obesity. Newer incretin therapies have demonstrated weight reduction between 15% to 25%, far outpacing non-incretin therapies for weight management and achieving levels of weight loss that may prevent weight-related complications. However, the discontinuation of incretin therapies is associated with weight regain. The main side effects of incretin therapies are transient, mild-to-moderate gastrointestinal side effects - nausea, diarrhea, constipation, and vomiting - that commonly occur in the first 4 to 8 weeks of treatment. There is a rich late-stage pipeline of incretin therapies for weight management, consisting of oral GLP-1 receptor agonists, dual GLP-1/GIP receptor agonists, dual GLP-1/glucagon receptor agonists, triple GLP-1/GIP/glucagon receptor agonists, and combination therapies with nonincretin drugs. Conclusion: Newer incretin therapies for weight management have the potential to improve the treatment for overweight and obesity, the treatment and prevention of weight-related complications, and the individualization of weight management. Ensuring that these therapies are accessible - and that treatment with them is consistent and sustainable - is necessary to translate findings from trials into the real world.
MeSH term(s)	Humans ; Incretins/therapeutic use ; Incretins/pharmacology ; Overweight/drug therapy ; Glucagon-Like Peptide 1/therapeutic use ; Gastric Inhibitory Polypeptide/pharmacology ; Gastric Inhibitory Polypeptide/therapeutic use ; Obesity Management ; Receptors, Glucagon/therapeutic use ; Diabetes Mellitus, Type 2/drug therapy ; Obesity/drug therapy ; Weight Loss ; Glucagon-Like Peptide-1 Receptor/agonists
Chemical Substances	Incretins ; Glucagon-Like Peptide 1 (89750-14-1) ; Gastric Inhibitory Polypeptide (59392-49-3) ; Receptors, Glucagon ; Glucagon-Like Peptide-1 Receptor
Language	English
Publishing date	2023-12-18
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1473503-9
ISSN	1530-891X
ISSN	1530-891X
DOI	10.1016/j.eprac.2023.12.010
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