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Article ; Online: Liver fibrosis for the dermatologist: a review.

Raahimi, Mina M / Livesey, Amy / Hamilton, Jessica / Shipman, Alexa R / Aspinall, Richard J

2023 Volume 48, Issue 4, Page(s) 303–309

Abstract: Methotrexate-induced liver fibrosis is not a well-defined pathology, and many of the reported cases can instead be classified as nonalcoholic fatty liver disease by current diagnostic criteria, which is particularly common in the psoriasis cohort. Liver ... ...

Abstract	Methotrexate-induced liver fibrosis is not a well-defined pathology, and many of the reported cases can instead be classified as nonalcoholic fatty liver disease by current diagnostic criteria, which is particularly common in the psoriasis cohort. Liver fibrosis usually takes many years to progress; therefore, screening for liver fibrosis should be done no more regularly than annually at the very most in dermatology practice. An algorithm is presented about how to investigate abnormal liver blood tests and screening tools for liver fibrosis are compared.
MeSH term(s)	Humans ; Dermatologists ; Liver Cirrhosis/complications ; Liver Cirrhosis/diagnosis ; Liver Cirrhosis/chemically induced ; Methotrexate/adverse effects ; Psoriasis/complications ; Psoriasis/diagnosis ; Non-alcoholic Fatty Liver Disease/complications ; Non-alcoholic Fatty Liver Disease/diagnosis ; Fibrosis
Chemical Substances	Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2023-02-09
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	195504-4
ISSN	1365-2230 ; 0307-6938
ISSN (online)	1365-2230
ISSN	0307-6938
DOI	10.1093/ced/llac083
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Article ; Online: TGF-β, to target or not to target; to prevent thyroid cancer progression?

Karnik, Isha / Sutherland, Rachel / Elson, Joanna / Aspinall, Sebastian / Meeson, Annette

Biochimica et biophysica acta. Reviews on cancer

2022 Volume 1877, Issue 4, Page(s) 188752

Abstract: Thyroid cancer (TC) is a common endocrine cancer with a rising incidence. Current treatment fails to eliminate aggressive thyroid tumours, prompting an investigation into the processes that cause disease progression. In this review, we provide insight ... ...

Abstract	Thyroid cancer (TC) is a common endocrine cancer with a rising incidence. Current treatment fails to eliminate aggressive thyroid tumours, prompting an investigation into the processes that cause disease progression. In this review, we provide insight into TGF-β driven epithelial to mesenchymal transition (EMT), summarizing the current literature surrounding thyroid carcinogenesis, and discuss the potential for therapeutic strategies targeting the TGF-β signalling pathway. Understanding the underlying mechanisms that regulate cancer stem cell (CSC) growth and TGF-β signalling may provide novel therapeutic approaches for highly resistant TCs.
MeSH term(s)	Epithelial-Mesenchymal Transition/physiology ; Humans ; Signal Transduction ; Thyroid Neoplasms/genetics ; Transforming Growth Factor beta/metabolism
Chemical Substances	Transforming Growth Factor beta
Language	English
Publishing date	2022-06-18
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2918802-7
ISSN	1879-2561 ; 0304-419X
ISSN (online)	1879-2561
ISSN	0304-419X
DOI	10.1016/j.bbcan.2022.188752
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Article: Alternative COVID-19 mitigation measures in school classrooms: analysis using an agent-based model of SARS-CoV-2 transmission.

Woodhouse, M J / Aspinall, W P / Sparks, R S J / Brooks-Pollock, E / Relton, C

Royal Society open science

2022 Volume 9, Issue 8, Page(s) 211985

Abstract: The SARS-CoV-2 epidemic has impacted children's education, with schools required to implement infection control measures that have led to periods of absence and classroom closures. We developed an agent-based epidemiological model of SARS-CoV-2 ... ...

Abstract	The SARS-CoV-2 epidemic has impacted children's education, with schools required to implement infection control measures that have led to periods of absence and classroom closures. We developed an agent-based epidemiological model of SARS-CoV-2 transmission in a school classroom that allows us to quantify projected infection patterns within primary school classrooms, and related uncertainties. Our approach is based on a contact model constructed using random networks, informed by structured expert judgement. The effectiveness of mitigation strategies in suppressing infection outbreaks and limiting pupil absence are considered. COVID-19 infections in primary schools in England in autumn 2020 were re-examined and the model was then used to estimate infection levels in autumn 2021, as the Delta variant was emerging and it was thought likely that school transmission would play a major role in an incipient new wave of the epidemic. Our results were in good agreement with available data. These findings indicate that testing-based surveillance is more effective than bubble quarantine, both for reducing transmission and avoiding pupil absence, even accounting for insensitivity of self-administered tests. Bubble quarantine entails large numbers of absences, with only modest impact on classroom infections. However, maintaining reduced contact rates within the classroom can have a major benefit for managing COVID-19 in school settings.
Language	English
Publishing date	2022-08-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2787755-3
ISSN	2054-5703
ISSN	2054-5703
DOI	10.1098/rsos.211985
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Conference proceedings ; Online: Analysis of magma flux and eruption intensity during the 2021 explosive activity at the Soufrière of St Vincent, West Indies

Sparks, S. / Aspinall, W. / Barclay, J. / Renfrew, I. / Contreras-Arratia, R. / Stewart, R.

XXVIII General Assembly of the International Union of Geodesy and Geophysics (IUGG)

2023

Abstract: Seismic RSAM signals and eruption cloud height measurements were used to estimate peak intensities of 40 explosive events during the 8-22 April 2021 activity of the Soufrière volcano. We estimated magma supply rates and erupted volumes in each explosion, ...

Abstract	Seismic RSAM signals and eruption cloud height measurements were used to estimate peak intensities of 40 explosive events during the 8-22 April 2021 activity of the Soufrière volcano. We estimated magma supply rates and erupted volumes in each explosion, characterized uncertainty by stochastic modelling and identified four eruptive stages. Stage 1 included an intense period of 9.5 hours with 11 explosive events with peak eruption intensity between 2000 and 4000 m 3 /s and magma supply rate reaching 828 m 3 /s. 12 high intensity explosions (~4000 m 3 /s) occurred in Stage 2 with average magma supply rate of 251 m 3 /s. Stage 3 involved declining intensity, magma supply rate and lengthening repose periods between explosions. Stage 4 involved 3 much weaker explosions. The total erupted volume of magma is estimated at 38.5 x 10 6 m 3 (90% credible interval: [22.0 . 61.9] x 10 6 m 3 ) consistent with independent estimates from analysis of tephra deposits and volcano subsidence sourced at ~6 km depth. The 150-fold increase in magma supply rate, from the preceding effusive phase to Stage 1 of the explosive phase, is attributed to replacement of very high viscosity degassed magma occupying the shallow conduit system with new lower viscosity volatile-rich magma from the magma chamber.
Subject code	333
Language	English
Publishing country	de
Document type	Conference proceedings ; Online
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Article: Pupils returning to primary schools in England during 2020: rapid estimations of punctual COVID-19 infection rates.

Aspinall, W P / Sparks, R S J / Woodhouse, M J / Cooke, R M / Scarrow, J H

Royal Society open science

2021 Volume 8, Issue 9, Page(s) 202218

Abstract: Drawing on risk methods from volcano crises, we developed a rapid COVID-19 infection model for the partial return of pupils to primary schools in England in June and July 2020, and a full return in September 2020. The model handles uncertainties in key ... ...

Abstract	Drawing on risk methods from volcano crises, we developed a rapid COVID-19 infection model for the partial return of pupils to primary schools in England in June and July 2020, and a full return in September 2020. The model handles uncertainties in key parameters, using a stochastic re-sampling technique, allowing us to evaluate infection levels as a function of COVID-19 prevalence and projected pupil and staff headcounts. Assuming average national adult prevalence, for the first scenario (as at 1 June 2020) we found that between 178 and 924 [90% CI] schools would have at least one infected individual, out of 16 769 primary schools in total. For the second return (July), our estimate ranged between 336 (2%) and 1873 (11%) infected schools. For a full return in September 2020, our projected range was 661 (4%) to 3310 (20%) infected schools, assuming the same prevalence as for 5 June. If national prevalence fell to one-quarter of that, the projected September range would decrease to between 381 (2%) and 900 (5%) schools but would increase to between 2131 (13%) and 9743 (58%) schools if prevalence increased to 4× June level. When regional variations in prevalence and school size distribution were included in the model, a slight decrease in the projected number of infected schools was indicated, but uncertainty on estimates increased markedly. The latter model variant indicated that 82% of infected schools would be in areas where prevalence exceeded the national average and the probability of multiple infected persons in a school would be higher in such areas.
Language	English
Publishing date	2021-09-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2787755-3
ISSN	2054-5703
ISSN	2054-5703
DOI	10.1098/rsos.202218
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Article ; Online: A remotely triggered fast neutron detection instrument based on a plastic organic scintillator.

Jones, A R / Aspinall, M D / Joyce, M J

The Review of scientific instruments

2018 Volume 89, Issue 2, Page(s) 23115

Abstract: A detector system for the characterization of radiation fields of both fast neutrons and γ rays is described comprising of a gated photomultiplier tube (PMT), an EJ299-33 solid organic scintillator detector, and an external trigger circuit. The objective ...

Abstract	A detector system for the characterization of radiation fields of both fast neutrons and γ rays is described comprising of a gated photomultiplier tube (PMT), an EJ299-33 solid organic scintillator detector, and an external trigger circuit. The objective of this development was to conceive a means by which the PMT in such a system can be actuated remotely during the high-intensity bursts of pulsed γ-ray contamination that can arise during active interrogation procedures. The system is used to detect neutrons and γ rays using established pulse-shape discrimination (PSD) techniques. The gating circuit enables the PMT to be switched off remotely. This is compatible with use during intense radiation transients to avoid saturation and the disruption of the operation of the PMT during the burst. Data are presented in the form of pulse-height spectra and PSD scatter plots for the system triggered with a strobed light source. These confirm that the gain of the system and the throughput for both triggered and un-triggered scenarios are as expected, given the duty cycle of the stimulating radiation. This demonstrates that the triggering function does not perturb the system response of the detector.
Language	English
Publishing date	2018-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	209865-9
ISSN	1089-7623 ; 0034-6748
ISSN (online)	1089-7623
ISSN	0034-6748
DOI	10.1063/1.5012121
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Article ; Online: Safety and efficacy of pyronaridine-artesunate paediatric granules in the treatment of uncomplicated malaria in children: insights from randomized clinical trials and a real-world study.

Ramharter, Michael / Djimde, Abdoulaye A / Borghini-Fuhrer, Isabelle / Miller, Robert / Shin, Jangsik / Aspinall, Adam / Richardson, Naomi / Wibberg, Martina / Fleckenstein, Lawrence / Arbe-Barnes, Sarah / Duparc, Stephan

Malaria journal

2024 Volume 23, Issue 1, Page(s) 61

Abstract: Background: Children are particularly at risk of malaria. This analysis consolidates the clinical data for pyronaridine-artesunate (PA) paediatric granules in children from three randomized clinical trials and a real-world study (CANTAM).: Methods: ... ...

Abstract	Background: Children are particularly at risk of malaria. This analysis consolidates the clinical data for pyronaridine-artesunate (PA) paediatric granules in children from three randomized clinical trials and a real-world study (CANTAM). Methods: An integrated safety analysis of individual patient data from three randomized clinical trials included patients with microscopically-confirmed Plasmodium falciparum, body weight ≥ 5 kg to < 20 kg, who received at least one dose of study drug (paediatric safety population). PA was administered once daily for 3 days; two trials included the comparator artemether-lumefantrine (AL). PCR-adjusted day 28 adequate clinical and parasitological response (ACPR) was evaluated. Real-world PA granules safety and effectiveness was also considered. Results: In the integrated safety analysis, 63.9% (95% CI 60.2, 67.4; 426/667) of patients had adverse events following PA and 62.0% (95% CI 56.9, 66.9; 222/358) with AL. Vomiting was more common with PA (7.8% [95% CI 6.0, 10.1; 52/667]) than AL (3.4% [95% CI 1.9, 5.8; 12/358]), relative risk 2.3 (95% CI 1.3, 4.3; P = 0.004), occurring mainly following the first PA dose (6.7%, 45/667), without affecting re-dosing or adherence. Prolonged QT interval occurred less frequently with PA (3.1% [95% CI 2.1, 4.8; 21/667]) than AL (8.1% [95% CI 5.7, 11.4; 29/358]), relative risk 0.39 (95% CI 0.22, 0.67; P = 0.0007). In CANTAM, adverse events were reported for 17.7% (95% CI 16.3, 19.2; 460/2599) of patients, most commonly vomiting (5.4% [95% CI 4.6, 6.4; 141/2599]), mainly following the first dose, (4.5% [117/2599]), with all patients successfully re-dosed, and pyrexia (5.4% [95% CI 4.6, 6.3; 140/2599]). In the two comparative clinical trials, Day 28 ACPR in the per-protocol population for PA was 97.1% (95% CI 94.6, 98.6; 329/339) and 100% (95% CI 99.3, 100; 514/514) versus 98.8% (95% CI 95.7, 99.9; 165/167) and 98.4% (95% CI 95.5, 99.7; 188/191) for AL, respectively. In CANTAM, PA clinical effectiveness was 98.0% (95% CI 97.3, 98.5; 2273/2320). Conclusions: Anti-malarial treatment with PA paediatric granules administered once daily for 3 days was well tolerated in children and displayed good clinical efficacy in clinical trials, with effectiveness confirmed in a real-world study. Trial registration Clinicaltrials.gov: SP-C-003-05: identifier NCT00331136; SP-C-007-07: identifier NCT0541385; SP-C-021-15: identifier NCT03201770. Pan African Clinical Trials Registry: SP-C-013-11: identifier PACTR201105000286876.
MeSH term(s)	Child ; Humans ; Antimalarials/adverse effects ; Artemether, Lumefantrine Drug Combination/therapeutic use ; Artemisinins/adverse effects ; Malaria, Falciparum/drug therapy ; Artemether/therapeutic use ; Randomized Controlled Trials as Topic ; Malaria/drug therapy ; Drug Combinations ; Treatment Outcome ; Vomiting/chemically induced ; Vomiting/drug therapy ; Ethanolamines/therapeutic use ; Artesunate ; Naphthyridines
Chemical Substances	pyronaridine tetraphosphate, artesunate drug combination ; Antimalarials ; Artemether, Lumefantrine Drug Combination ; Artemisinins ; Artemether (C7D6T3H22J) ; Drug Combinations ; Ethanolamines ; Artesunate (60W3249T9M) ; Naphthyridines
Language	English
Publishing date	2024-02-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2091229-8
ISSN	1475-2875 ; 1475-2875
ISSN (online)	1475-2875
ISSN	1475-2875
DOI	10.1186/s12936-024-04885-3
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Article: A novel approach for evaluating contact patterns and risk mitigation strategies for COVID-19 in English primary schools with application of structured expert judgement.

Sparks, R S J / Aspinall, W P / Brooks-Pollock, E / Cooke, R M / Danon, L / Barclay, J / Scarrow, J H / Cox, J

Royal Society open science

2021 Volume 8, Issue 1, Page(s) 201566

Abstract: Personal contacts drive COVID-19 infections. After being closed (23 March 2020) UK primary schools partially re-opened on 1 June 2020 with social distancing and new risk mitigation strategies. We conducted a structured expert elicitation of teachers to ... ...

Abstract	Personal contacts drive COVID-19 infections. After being closed (23 March 2020) UK primary schools partially re-opened on 1 June 2020 with social distancing and new risk mitigation strategies. We conducted a structured expert elicitation of teachers to quantify primary school contact patterns and how contact rates changed upon re-opening with risk mitigation measures in place. These rates, with uncertainties, were determined using a performance-based algorithm. We report mean number of contacts per day for four cohorts within schools, with associated 90% confidence ranges. Prior to lockdown, younger children (Reception and Year 1) made 15 contacts per day [range 8.35] within school, older children (Year 6) 18 contacts [range 5.55], teaching staff 25 contacts [range 4.55] and non-classroom staff 11 contacts [range 2.27]. After re-opening, the mean number of contacts was reduced by 53% for young children, 62% for older children, 60% for classroom staff and 64% for other staff. Contacts between teaching and non-teaching staff reduced by 80%. The distributions of contacts per person are asymmetric with heavy tail reflecting a few individuals with high contact numbers. Questions on risk mitigation and supplementary structured interviews elucidated how new measures reduced daily contacts in-school and contribute to infection risk reduction.
Language	English
Publishing date	2021-01-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2787755-3
ISSN	2054-5703
ISSN	2054-5703
DOI	10.1098/rsos.201566
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Article ; Online: Impact of transforming growth factor beta 1 on normal and thyroid cancer side population cells.

Latar, Nani Md / Mahkamova, Kamilla / Elson, Joanna / Karnik, Isha / Sutherland, Rachel / Aspinall, Sebastian / Meeson, Annette

Endocrine

2022 Volume 76, Issue 2, Page(s) 359–368

Abstract: Purpose: To determine the impact of exogenous transforming growth factor beta 1 (TGF-β1) on side population (SP) cells isolated from normal, papillary thyroid cancer and anaplastic thyroid cancer cell lines and from human thyroid tissues.: Methods: ... ...

Abstract	Purpose: To determine the impact of exogenous transforming growth factor beta 1 (TGF-β1) on side population (SP) cells isolated from normal, papillary thyroid cancer and anaplastic thyroid cancer cell lines and from human thyroid tissues. Methods: All cell populations were stained with Hoechst 33342 and analysed using dual wavelength flow cytometry to identify SP cells. This SP assay was used to assess the impact of TGF-β1 treatment and withdrawal of treatment on SP percentages. Semi-quantitative and quantitative PCR were used for molecular analysis of cells pre and post TGF-β1 treatment. Results: All cell lines expressed mRNA for both TGFB1 and its receptors, as well as showing variable expression of CDH1 and CDH2, with expressing of CDH1 being highest and CDH2 being lowest in the normal cell line. Exposure to exogenous TGF-β1 resulted in a reduction in mRNA expression of ABCG2 compared to controls which was significant between control and treated cancer cell lines. SP cells were isolated from primary human thyroid tissues, with numbers being significantly higher in papillary thyroid cancers. Exposure to TGF-β1 decreased the SP percentage in both thyroid cancer cell lines and completely abrogated these cells in the primary papillary thyroid cancer cultures. On withdrawal of TGF-β1 the SP phenotype was restored in the cancer cell lines and SP percentages increased to above that of untreated cells. Conclusions: TGF-β1 exposure transiently regulates thyroid cancer SP cells, leading to a reduction in SP percentages, while withdrawal of TGF-β1 results in restoration of the SP phenotype.
MeSH term(s)	Humans ; RNA, Messenger/analysis ; Side-Population Cells/metabolism ; Thyroid Cancer, Papillary/genetics ; Thyroid Neoplasms/genetics ; Thyroid Neoplasms/metabolism ; Transforming Growth Factor beta/metabolism ; Transforming Growth Factor beta1/metabolism
Chemical Substances	RNA, Messenger ; Transforming Growth Factor beta ; Transforming Growth Factor beta1
Language	English
Publishing date	2022-02-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	1194484-5
ISSN	1559-0100 ; 1355-008X ; 0969-711X
ISSN (online)	1559-0100
ISSN	1355-008X ; 0969-711X
DOI	10.1007/s12020-022-02990-4
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Zs.A 3884: Show issues

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Article ; Online: Using remote sensing to assess peatland resilience by estimating soil surface moisture and drought recovery.

Lees, K J / Artz, R R E / Chandler, D / Aspinall, T / Boulton, C A / Buxton, J / Cowie, N R / Lenton, T M

The Science of the total environment

2020 Volume 761, Page(s) 143312

Abstract: Peatland areas provide a range of ecosystem services, including biodiversity, carbon storage, clean water, and flood mitigation, but many areas of peatland in the UK have been degraded through human land use including drainage. Here, we explore whether ... ...

Abstract	Peatland areas provide a range of ecosystem services, including biodiversity, carbon storage, clean water, and flood mitigation, but many areas of peatland in the UK have been degraded through human land use including drainage. Here, we explore whether remote sensing can be used to monitor peatland resilience to drought. We take resilience to mean the rate at which a system recovers from perturbation; here measured literally as a recovery timescale of a soil surface moisture proxy from drought lowering. Our objectives were (1) to assess the reliability of Sentinel-1 Synthetic Aperture Radar (SAR) backscatter as a proxy for water table depth (WTD); (2) to develop a method using SAR to estimate below-ground (hydrological) resilience of peatlands; and (3) to apply the developed method to different sites and consider the links between resilience and land management. Our inferences of WTD from Sentinel-1 SAR data gave results with an average Pearson's correlation of 0.77 when compared to measured WTD values. The 2018 summer drought was used to assess resilience across three different UK peatland areas (Dartmoor, the Peak District, and the Flow Country) by considering the timescale of the soil moisture proxy recovery. Results show clear areas of lower resilience within all three study sites, which often correspond to areas of high drainage and may be particularly vulnerable to increasing drought severity/events under climate change. This method is applicable to monitoring peatland resilience elsewhere over larger scales, and could be used to target restoration work towards the most vulnerable areas.
Language	English
Publishing date	2020-11-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	121506-1
ISSN	1879-1026 ; 0048-9697
ISSN (online)	1879-1026
ISSN	0048-9697
DOI	10.1016/j.scitotenv.2020.143312
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