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Article: The

Osborne, Olivia J / Boobis, Alan / Botham, Phil / Price, Shirley Christine / Kuhnle, Gunter C / Mulholland, Cath / Potter, Claire / Gott, David

Toxicology research

2024 Volume 13, Issue 2, Page(s) tfae016

Abstract: The further optimization of consumer safety through risk assessment of chemicals present in food will require adaptability and flexibility to utilize the accelerating developments in safety science and technology. New Approach Methodologies (NAMs) are ... ...

Abstract	The further optimization of consumer safety through risk assessment of chemicals present in food will require adaptability and flexibility to utilize the accelerating developments in safety science and technology. New Approach Methodologies (NAMs) are gaining traction as a systematic approach to support informed decision making in chemical risk assessment. The vision is to be able to predict risk more accurately, rapidly and efficiently. The opportunity exists now to use these approaches which requires a strategy to translate the science into future regulatory implementation. Here we discuss new insights obtained from three recent workshops on how to translate the science into future regulatory implementation. To assist the UK in this endeavor, the Food Standards Agency (FSA) and the scientific advisory committee on chemical toxicity (COT) have been developing a roadmap. In addition, we discuss how these new insights fit into the bigger picture of the new chemical landscape for better consumer safety and the importance of international harmonization.
Language	English
Publishing date	2024-03-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2684701-2
ISSN	2045-4538 ; 2045-452X
ISSN (online)	2045-4538
ISSN	2045-452X
DOI	10.1093/toxres/tfae016
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: High-resolution precipitation monitoring with a dense seismic nodal array.

Hua, Junlin / Wu, Mengxi / Mulholland, Jake P / Neelin, J David / Tsai, Victor C / Trugman, Daniel T

Scientific reports

2023 Volume 13, Issue 1, Page(s) 11450

Abstract: Accurate precipitation monitoring is crucial for understanding climate change and rainfall-driven hazards at a local scale. However, the current suite of monitoring approaches, including weather radar and rain gauges, have different insufficiencies such ... ...

Abstract	Accurate precipitation monitoring is crucial for understanding climate change and rainfall-driven hazards at a local scale. However, the current suite of monitoring approaches, including weather radar and rain gauges, have different insufficiencies such as low spatial and temporal resolution and difficulty in accurately detecting potentially destructive precipitation events such as hailstorms. In this study, we develop an array-based method to monitor rainfall with seismic nodal stations, offering both high spatial and temporal resolution. We analyze seismic records from 1825 densely spaced, high-frequency seismometers in Oklahoma, and identify signals from nine precipitation events that occurred during the one-month station deployment in 2016. After removing anthropogenic noise and Earth structure response, the obtained precipitation spatial pattern mimics the one from a nearby operational weather radar, while offering higher spatial (~ 300 m) and temporal (< 10 s) resolution. We further show the potential of this approach to monitor hail with joint analysis of seismic intensity and independent precipitation rate measurements, and advocate for coordinated seismological-meteorological field campaign design.
MeSH term(s)	Weather ; Rain ; Oklahoma ; Radar ; Climate Change
Language	English
Publishing date	2023-07-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-38008-w
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Article ; Online: Investigating the linkage between mesopic spatial summation and variations in retinal ganglion cell density across the central visual field.

Hunter, Aoife M L / Anderson, Roger S / Redmond, Tony / Garway-Heath, David F / Mulholland, Pádraig J

Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)

2023 Volume 43, Issue 5, Page(s) 1179–1189

Abstract: Purpose: The relationship between perimetric stimulus area and Ricco's area (RA) determines measured thresholds and the sensitivity of perimetry to retinal disease. The nature of this relationship, in addition to effect of retinal ganglion cell (RGC) ... ...

Abstract	Purpose: The relationship between perimetric stimulus area and Ricco's area (RA) determines measured thresholds and the sensitivity of perimetry to retinal disease. The nature of this relationship, in addition to effect of retinal ganglion cell (RGC) number on this, is currently unknown for the adaptation conditions of mesopic microperimetry. In this study, achromatic mesopic spatial summation was measured across the central visual field to estimate RA with the number of RGCs underlying RA also being established. Methods: Achromatic luminance thresholds were measured for six incremental spot stimuli (0.009-2.07 deg Results: Ricco's area exhibited a small but statistically insignificant increase between 2.5° and 10° eccentricity. Compared with photopic conditions, RA was larger, with the difference between RA and the Goldmann III stimulus (0.43°) being minimised. RGC number underlying RA was also higher than reported for photopic conditions (median 70 cells, IQR 36-93), with no significant difference being observed across test locations. Conclusions: Ricco's area and the number of RGCs underlying RA do not vary significantly across the central visual field in mesopic conditions. However, RA is larger and more similar to the standard perimetric Goldmann III stimulus under mesopic compared with photopic adaptation conditions. Further work is required to determine if compensatory enlargements in RA occur in age-related macular degeneration, to establish the optimal stimulus parameters for AMD-specific microperimetry.
MeSH term(s)	Humans ; Middle Aged ; Visual Fields ; Retinal Ganglion Cells ; Visual Field Tests ; Regression Analysis ; Color Vision
Language	English
Publishing date	2023-04-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604564-9
ISSN	1475-1313 ; 0275-5408
ISSN (online)	1475-1313
ISSN	0275-5408
DOI	10.1111/opo.13158
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Article: Tumor Heterogeneity and Consequences for Bladder Cancer Treatment.

Lavallee, Etienne / Sfakianos, John P / Mulholland, David J

Cancers

2021 Volume 13, Issue 21

Abstract: Acquired therapeutic resistance remains a major challenge in cancer management and associates with poor oncological outcomes in most solid tumor types. A major contributor is tumor heterogeneity (TH) which can be influenced by the stromal; immune and ... ...

Abstract	Acquired therapeutic resistance remains a major challenge in cancer management and associates with poor oncological outcomes in most solid tumor types. A major contributor is tumor heterogeneity (TH) which can be influenced by the stromal; immune and epithelial tumor compartments. We hypothesize that heterogeneity in tumor epithelial subpopulations-whether de novo or newly acquired-closely regulate the clinical course of bladder cancer. Changes in these subpopulations impact the tumor microenvironment including the extent of immune cell infiltration and response to immunotherapeutics. Mechanisms driving epithelial tumor heterogeneity (EpTH) can be broadly categorized as mutational and non-mutational. Mechanisms regulating lineage plasticity; acquired cellular mutations and changes in lineage-defined subpopulations regulate stress responses to clinical therapies. If tumor heterogeneity is a dynamic process; an increased understanding of how EpTH is regulated is critical in order for clinical therapies to be more sustained and durable. In this review and analysis, we assess the importance and regulatory mechanisms governing EpTH in bladder cancer and the impact on treatment response.
Language	English
Publishing date	2021-10-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13215297
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Article ; Online: Investigating the Spatiotemporal Summation of Perimetric Stimuli in Dry Age-Related Macular Degeneration.

Hunter, Aoife M L / Anderson, Roger S / Redmond, Tony / Garway-Heath, David F / Mulholland, Pádraig J

Translational vision science & technology

2023 Volume 12, Issue 11, Page(s) 37

Abstract: Purpose: To measure achromatic spatial, temporal, and spatiotemporal summation in dry age-related macular degeneration (AMD) compared to healthy controls under conditions of photopic gaze-contingent perimetry.: Methods: Twenty participants with dry ... ...

Abstract	Purpose: To measure achromatic spatial, temporal, and spatiotemporal summation in dry age-related macular degeneration (AMD) compared to healthy controls under conditions of photopic gaze-contingent perimetry. Methods: Twenty participants with dry AMD (mean age, 74.6 years) and 20 healthy controls (mean age, 67.8 years) performed custom, gaze-contingent perimetry tests. An area-modulation test generated localized estimates of Ricco's area (RA) at 2.5° and 5° eccentricities along the 0°, 90°, 180°, and 270° meridians. Contrast thresholds were measured at the same test locations for stimuli of six durations (3.7-190.4 ms) with a Goldmann III stimulus (GIII, 0.43°) and RA-scaled stimuli. The upper limit (critical duration) of complete temporal summation (using the GIII stimulus) and spatiotemporal summation (using the RA stimuli) was estimated using iterative two-phase regression analysis. Results: Median (interquartile range [IQR]) RA estimates were significantly larger in AMD participants (2.5°: 0.21 [0.09-0.41] deg2; 5°: 0.32 [0.15-0.65 deg2]) compared to healthy controls (2.5°: 0.08 [0.05-0.13] deg2; 5°: 0.15 [0.08-0.22] deg2) at all test locations (all P < 0.05). No significant difference in median critical duration was found in AMD participants with the GIII stimulus (19.6 [9.9-30.4] ms) and RA-scaled stimuli (22.9 [13.9-40.3] ms) compared to healthy controls (GIII: 17.0 [11.3-24.0] ms; RA-scaled: 22.4 [14.3-33.1] ms) at all test locations (all P > 0.05). Conclusions: Spatial summation is altered in dry AMD, without commensurate changes in temporal summation. Translational relevance: The sensitivity of perimetry to AMD may be improved by utilizing stimuli that probe alterations in spatial summation in the disease.
MeSH term(s)	Humans ; Aged ; Visual Field Tests ; Geographic Atrophy/diagnosis
Language	English
Publishing date	2023-11-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2674602-5
ISSN	2164-2591 ; 2164-2591
ISSN (online)	2164-2591
ISSN	2164-2591
DOI	10.1167/tvst.12.11.37
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Book: Laser hair removal

Goldberg, David J. / Bialoglow, Tom / Mulholland, Steven

(Series in cosmetic and laser therapy ; [5])

2008

Author's details	David J. Goldberg with contributions from Tom Bialoglow and Steven Mulholland
Series title	Series in cosmetic and laser therapy ; [5]
Collection
Keywords	Hair Removal / instrumentation ; Hair Removal / methods ; Laser Therapy
Language	English
Size	VIII, 224 S. : Ill., graph. Darst.
Edition	2. ed.
Publisher	Informa Healthcare
Publishing place	London u.a.
Publishing country	Great Britain
Document type	Book
Note	Bandzählung stammt aus einer Auflistung in Band 7
HBZ-ID	HT015601420
ISBN	978-0-415-41412-8 ; 0-415-41412-1
Database	Catalogue ZB MED Medicine, Health

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2008 A 4131	order for loan	Magazin

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Article ; Online: Spatiotemporal summation of perimetric stimuli in healthy observers.

Montesano, Giovanni / Mulholland, Pádraig J / Garway-Heath, David F / Evans, Josephine / Ometto, Giovanni / Crabb, David P

Journal of vision

2023 Volume 23, Issue 4, Page(s) 2

Abstract: Spatial summation of perimetric stimuli has been used to derive conclusions about the spatial extent of retinal-cortical convergence, mostly from the size of the critical area of summation (Ricco's area, RA) and critical number of retinal ganglion cells ( ...

Abstract	Spatial summation of perimetric stimuli has been used to derive conclusions about the spatial extent of retinal-cortical convergence, mostly from the size of the critical area of summation (Ricco's area, RA) and critical number of retinal ganglion cells (RGCs). However, spatial summation is known to change dynamically with stimulus duration. Conversely, temporal summation and critical duration also vary with stimulus size. Such an important and often neglected spatiotemporal interaction has important implications for modeling perimetric sensitivity in healthy observers and for formulating hypotheses for changes measured in disease. In this work, we performed experiments on visually heathy observers confirming the interaction of stimulus size and duration in determining summation responses in photopic conditions. We then propose a simplified computational model that captures these aspects of perimetric sensitivity by modelling the total retinal input, the combined effect of stimulus size, duration, and retinal cones-to-RGC ratio. We additionally show that, in the macula, the enlargement of RA with eccentricity might not correspond to a constant critical number of RGCs, as often reported, but to a constant critical total retinal input. We finally compare our results with previous literature and show possible implications for modeling disease, especially glaucoma.
MeSH term(s)	Humans ; Visual Fields ; Visual Field Tests/methods ; Retina/physiology ; Retinal Ganglion Cells/physiology ; Retinal Cone Photoreceptor Cells/physiology
Language	English
Publishing date	2023-04-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2106064-2
ISSN	1534-7362 ; 1534-7362
ISSN (online)	1534-7362
ISSN	1534-7362
DOI	10.1167/jov.23.4.2
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Article ; Online: Simulated cataract surgery training of the non-dominant hand improves confidence and competence.

Hind, Jennifer / Mulholland, Carl / Cox, Alan / Lockington, David

Eye (London, England)

2022 Volume 36, Issue 11, Page(s) 2211–2212

MeSH term(s)	Humans ; Ophthalmology/education ; Cataract Extraction/education ; Cataract ; Clinical Competence ; Internship and Residency ; Education, Medical, Graduate
Language	English
Publishing date	2022-02-25
Publishing country	England
Document type	Journal Article
ZDB-ID	91001-6
ISSN	1476-5454 ; 0950-222X
ISSN (online)	1476-5454
ISSN	0950-222X
DOI	10.1038/s41433-022-01993-9
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Article ; Online: The emerging potential of interactive virtual reality in drug discovery.

Walters, Rebecca K / Gale, Ella M / Barnoud, Jonathan / Glowacki, David R / Mulholland, Adrian J

Expert opinion on drug discovery

2022 Volume 17, Issue 7, Page(s) 685–698

Abstract: Introduction: The potential of virtual reality (VR) to contribute to drug design and development has been recognized for many years. A recent advance is to use VR not only to visualize and interact with molecules, but also to interact with molecular ... ...

Abstract	Introduction: The potential of virtual reality (VR) to contribute to drug design and development has been recognized for many years. A recent advance is to use VR not only to visualize and interact with molecules, but also to interact with molecular dynamics simulations 'on the fly' (interactive molecular dynamics in VR, IMD-VR), which is useful for flexible docking and examining binding processes and conformational changes. Areas covered: The authors use the term 'interactive VR' to refer to software where interactivity is an inherent part of the user VR experience Expert opinion: The ease of viewing and manipulating molecular structures and dynamics, using accessible VR hardware, and the ability to modify structures on the fly (
MeSH term(s)	Drug Design ; Drug Discovery ; Molecular Dynamics Simulation ; Software ; Virtual Reality
Language	English
Publishing date	2022-06-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2259618-5
ISSN	1746-045X ; 1746-0441
ISSN (online)	1746-045X
ISSN	1746-0441
DOI	10.1080/17460441.2022.2079632
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Article ; Online: Free energy along drug-protein binding pathways interactively sampled in virtual reality.

Deeks, Helen M / Zinovjev, Kirill / Barnoud, Jonathan / Mulholland, Adrian J / van der Kamp, Marc W / Glowacki, David R

Scientific reports

2023 Volume 13, Issue 1, Page(s) 16665

Abstract: We describe a two-step approach for combining interactive molecular dynamics in virtual reality (iMD-VR) with free energy (FE) calculation to explore the dynamics of biological processes at the molecular level. We refer to this combined approach as iMD- ... ...

Abstract	We describe a two-step approach for combining interactive molecular dynamics in virtual reality (iMD-VR) with free energy (FE) calculation to explore the dynamics of biological processes at the molecular level. We refer to this combined approach as iMD-VR-FE. Stage one involves using a state-of-the-art 'human-in-the-loop' iMD-VR framework to generate a diverse range of protein-ligand unbinding pathways, benefitting from the sophistication of human spatial and chemical intuition. Stage two involves using the iMD-VR-sampled pathways as initial guesses for defining a path-based reaction coordinate from which we can obtain a corresponding free energy profile using FE methods. To investigate the performance of the method, we apply iMD-VR-FE to investigate the unbinding of a benzamidine ligand from a trypsin protein. The binding free energy calculated using iMD-VR-FE is similar for each pathway, indicating internal consistency. Moreover, the resulting free energy profiles can distinguish energetic differences between pathways corresponding to various protein-ligand conformations (e.g., helping to identify pathways that are more favourable) and enable identification of metastable states along the pathways. The two-step iMD-VR-FE approach offers an intuitive way for researchers to test hypotheses for candidate pathways in biomolecular systems, quickly obtaining both qualitative and quantitative insight.
MeSH term(s)	Humans ; Protein Binding ; Ligands ; Proteins ; Molecular Dynamics Simulation ; Virtual Reality
Chemical Substances	Ligands ; Proteins
Language	English
Publishing date	2023-10-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-43523-x
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