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Predicting visual acuity from visual field sensitivity in age-related macular degenerationDenniss, Jonathan, Baggaley, H.C., Astle, A.T. January 2018 (has links)
Yes / Purpose: To investigate how well visual field sensitivity predicts visual acuity at the same locations in macular disease, and to assess whether such predictions may be useful for selecting an optimum area for fixation training.
Methods: Visual field sensitivity and acuity were measured at nine locations in the central 10° in 20 people with AMD and stable foveal fixation. A linear mixed model was constructed to predict acuity from sensitivity, taking into account within-subject effects and eccentricity. Cross validation was used to test the ability to predict acuity from sensitivity in a new patient. Simulations tested whether sensitivity can predict nonfoveal regions with greatest acuity in individual patients.
Results: Visual field sensitivity (P < 0.0001), eccentricity (P = 0.007), and random effects of subject on eccentricity (P = 0.043) improved the model. For known subjects, 95% of acuity prediction errors (predicted − measured acuity) fell within −0.21 logMAR to +0.18 logMAR (median +0.00 logMAR). For unknown subjects, cross validation gave 95% of acuity prediction errors within −0.35 logMAR to +0.31 logMAR (median −0.01 logMAR). In simulations, the nonfoveal location with greatest predicted acuity had greatest “true” acuity on median 26% of occasions, and median difference in acuity between the location with greatest predicted acuity and the best possible location was +0.14 logMAR (range +0.04 to +0.17).
Conclusions: The relationship between sensitivity and acuity in macular disease is not strongly predictive. The location with greatest sensitivity on microperimetry is unlikely to represent the location with the best visual acuity, even if eccentricity is taken into account. / College of Optometrists Postdoctoral Research Award (JD and ATA; London, UK) and National Institute for Health Research (NIHR) Postdoctoral Fellowship (ATA; London, UK). Presents independent research funded by the NIHR. / Research Development Fund Publication Prize Award winner, August 2018.
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The effect of territorial stigmatisation processes on ontological security: A case-study of Bradford politicsSullivan, Paul W., Akhtar, Parveen 29 October 2018 (has links)
Yes / We investigate the effect of territorial stigmatisation on ontological security through a qualitative case-study of Bradford politics during the 2015 General Election. Territorial stigmatisation and ontological security are important constructs in political geography but there is relatively little research on how territorial stigmatisation effects ontological security in everyday lived experience – in this case, the lived experience of political contests.
We conducted thirty in-depth interviews, generated three themes and present and analyse these three themes in the form of three ‘created dialogues’ as outlined by Sullivan (2012), with a smaller sample of ten out of thirty of our participants. Drawing on Bakhtin’s (1981) concept of ‘chronotope’ we identity three key effects of territorial stigmatisation on ontological security: i) A negative reputation of ‘parallel societies’ has the potential to create double meanings for the inhabitants of that society; ii) Local reputation enhances ontological security through linking particular places to particular personalities but potentially decreases ontological security for a district as a whole; iii) Everyday lived experiences sometimes acquire charged emotional symbolic significance, which could encourage the reflexive side of ontological security. Our findings went through a positive member-checking process with five of the participants. / Research Development Fund Publication Prize Award winner, October 2018.
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Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trialHull, M.A., Sprange, K., Hepburn, T., Tan, W., Shafayat, A., Rees, C.J., Clifford, G., Logan, R.F., Loadman, Paul, Williams, E.A., Whitham, D., Montgomery, A.A. 19 November 2018 (has links)
Yes / Background: The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and aspirin both have proof of
concept for colorectal cancer chemoprevention, aligned with an excellent safety profile. Therefore, we aimed to test
the efficacy of EPA and aspirin, alone and in combination and compared with a placebo, in individuals with sporadic
colorectal neoplasia detected at colonoscopy.
Methods: In a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial, patients aged 55–73 years
who were identified during colonoscopy as being at high risk in the English Bowel Cancer Screening Programme
(BCSP; ≥3 adenomas if at least one was ≥10 mm in diameter or ≥5 adenomas if these were <10 mm in diameter) were
recruited from 53 BCSP endoscopy units in England, UK. Patients were randomly allocated (1:1:1:1) using a secure
web-based server to receive 2 g EPA-free fatty acid (FFA) per day (either as the FFA or triglyceride), 300 mg aspirin per
day, both treatments in combination, or placebo for 12 months using random permuted blocks of randomly varying
size, and stratified by BCSP site. Research staff and participants were masked to group assignment. The primary
endpoint was the adenoma detection rate (ADR; the proportion of participants with any adenoma) at 1 year surveillance
colonoscopy analysed in all participants with observable follow-up data using a so-called at-the-margins approach,
adjusted for BCSP site and repeat endoscopy at baseline. The safety population included all participants who received
at least one dose of study drug. The trial is registered with the International Standard Randomised Controlled Trials
Number registry, number ISRCTN05926847.
Findings: Between Nov 11, 2011, and June 10, 2016, 709 participants were randomly assigned to four treatment groups
(176 to placebo, 179 to EPA, 177 to aspirin, and 177 to EPA plus aspirin). Adenoma outcome data were available for
163 (93%) patients in the placebo group, 153 (85%) in the EPA group, 163 (92%) in the aspirin group, and 161 (91%) in
the EPA plus aspirin group. The ADR was 61% (100 of 163) in the placebo group, 63% (97 of 153) in the EPA group,
61% (100 of 163) in the aspirin group, and 61% (98 of 161) in the EPA plus aspirin group, with no evidence of any
effect for EPA (risk ratio [RR] 0·98, 95% CI 0·87 to 1·12; risk difference –0·9%, –8·8 to 6·9; p=0·81) or aspirin
(RR 0·99 (0·87 to 1·12; risk difference –0·6%, –8·5 to 7·2; p=0·88). EPA and aspirin were well tolerated (78 [44%] of
176 had ≥1 adverse event in the placebo group compared with 82 [46%] in the EPA group, 68 [39%] in the aspirin
group, and 76 [45%] in the EPA plus aspirin group), although the number of gastrointestinal adverse events was
increased in the EPA alone group at 146 events (compared with 85 in the placebo group, 86 in the aspirin group, and
68 in the aspirin plus placebo group). Six upper-gastrointestinal bleeding events were reported across the treatment
groups (two in the EPA group, three in the aspirin group, and one in the placebo group).
Interpretation Neither EPA nor aspirin treatment were associated with a reduction in the proportion of patients with
at least one colorectal adenoma. Further research is needed regarding the effect on colorectal adenoma number
according to adenoma type and location. Optimal use of EPA and aspirin might need a precision medicine approach
to adenoma recurrence. / Efficacy and Mechanism Evaluation Programme, a UK Medical Research Council and National Institute for Health Research partnership. / Research Development Fund Publication Prize Award winner, November 2018.
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Influence of positive and negative dimensions of dementia caregiving on caregiver well-being and satisfaction with life: Findings from the IDEAL studyQuinn, Catherine, Nelis, S.M., Martyr, A., Victor, C., Morris, R.G. 08 April 2019 (has links)
Yes / The aim of this study was to identify the potential impact of positive and negative dimensions of caregiving on caregiver well-being and satisfaction with life (SwL).
This study used time-point one data from the Improving the experience of Dementia and Enhancing Active Life (also known as IDEAL)cohort study that involved 1,283 informal caregivers of people in the mild-to-moderate stages of dementia recruited from 29 sites within Great Britain. Multivariate linear regression modeling was used to investigate the associations between positive dimensions of caregiving (measured by caregiving competence and perceptions of positive aspects of caregiving), negative dimensions of caregiving (measured by caregiving stress and role captivity), and caregiver well-being and SwL.
Lower well-being was associated with low caregiving competence (–13.77; 95% confidence interval [CI]:–16.67, –10.87), perceiving fewer positive aspects of caregiving (–7.67; 95% CI:–10.26, –5.07), high caregiving stress (–24.45; 95% CI:–26.94, –21.96), and high role captivity (–15.61; 95% CI:–18.33, –12.89). Lower SwL was associated with low caregiving competence (–4.61; 95% CI:–5.57, –3.66), perceiving fewer positive aspects of caregiving (–3.09; 95% CI:–3.94, –2.25), high caregiving stress (–7.88; 95% CI:–8.71, –7.06), and high role captivity (–6.41; 95% CI:–7.27, –5.54). When these four measures were combined within the same model, only positive aspects of caregiving and caregiving stress retained independent associations with well-being and SwL.
Both positive and negative dimensions of caregiving were associated with caregiver well-being and SwL. Psychological therapies and interventions need to consider not only the negative aspects of caregiving but also positive caregiving experiences and their implications for caregiver well-being and SwL. / Research Development Fund Publication Prize Award winner, February 2019. The IDEAL data will be deposited with the UK Data Archive upon completion of the study. Details on how the data can be accessed will be made available on the project website www.idealproject.org.uk.
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Asymmetries between achromatic and chromatic extraction of 3D motion signalsKaestner, M., Maloney, R.T., Wailes-Newson, K.H., Bloj, Marina, Harris, J.M., Morland, A.B., Wade, A.R. 21 June 2019 (has links)
Yes / Motion in depth (MID) can be cued by high-resolution changes in binocular disparity over time (CD), and low-resolution interocular velocity differences (IOVD). Computational differences between these two mechanisms suggest that they may be implemented in visual pathways with different spatial and temporal resolutions. Here, we used fMRI to examine how achromatic and S-cone signals contribute to human MID perception. Both CD and IOVD stimuli evoked responses in a widespread network that included early visual areas, parts of the dorsal and ventral streams, and motion-selective area hMT+. Crucially, however, we measured an interaction between MID type and chromaticity. fMRI CD responses were largely driven by achromatic stimuli, but IOVD responses were better driven by isoluminant S-cone inputs. In our psychophysical experiments, when S-cone and achromatic stimuli were matched for perceived contrast, participants were equally sensitive to the MID in achromatic and S-cone IOVD stimuli. In comparison, they were relatively insensitive to S-cone CD. These findings provide evidence that MID mechanisms asymmetrically draw on information in precortical pathways. An early opponent motion signal optimally conveyed by the S-cone pathway may provide a substantial contribution to the IOVD mechanism. / Supported by the Biotechnology and Biological Sciences Research Council Grants BB/M002543/1 (to A.R.W.), BB/M001660/1 (to J.M.H.), and BB/M001210/1 (to M.B.). / Research Development Fund Publication Prize Award winner, May 2019.
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The whole tooth and nothing but the tooth: or why temporal resolution of bone collagen may be unreliableBeaumont, Julia 10 February 2020 (has links)
Yes / The carbon (δ13C) and nitrogen (δ15N) isotope ratios of human bone collagen have been used extensively over the last 40 years to investigate the diet of past populations. It has become apparent that bone collagen can give an unreliable temporal dietary signature especially in juveniles. With higher temporal resolution sampling of collagen from tooth dentine, it is possible to identify short‐term changes in diet previously invisible in bone. This paper discusses the inherent problems of using bone collagen for dietary studies and suggests better sample choices which can make our interpretations more robust, using breastfeeding and weaning as an example. / The modern data was collected and analysed using funding from the Rank Prize Funds New Investigator Award and sponsorship from DB Orthodontics, Bradford. The Tooth Fairy team acknowledges the support of the National Institute for Health Research Clinical Research Network (NIHR CRN). / Research Development Fund Publication Prize Award winner, February 2020.
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The role of cultural heritage in visitor narratives of peatlands: analysis of online user-generated reviews from three peatland sites in EnglandFlint, Abbi, Jennings, Benjamin R. 23 June 2021 (has links)
Yes / User-generated reviews of visitor attractions, on publicly available websites,
such as Tripadvisor, are frequently used in tourism research but
feature less often in published cultural heritage research. In this paper,
we describe a qualitative analysis of the text from user-generated reviews
of three peatland heritage landscapes in the United Kingdom – Ilkley
Moor, Thorne and Hatfield Moors, and Shapwick Heath – to better understand
the role tangible and intangible cultural heritage play in visitor
perceptions and narratives of these sites. Our analysis indicates that
visitors tend to emphasise natural over cultural heritage of peatland
landscapes and hold plural, highly contextual and sometimes dissonant
perceptions; there is no single story of peatlands. This presents both
challenges and opportunities for building public appreciation of peatland
cultural heritage. User-generated reviews offer, as-yet under-explored,
potential data for use by heritage researchers and managers who seek
to explore how visitors understand and use sites, and may also contribute
to the emerging intangible heritage of heritage landscapes. / Research Development Fund Publication Prize Award winner, June 2021.
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Intermittent PI3Ko inhibition sustains anti-tumor immunity and curbs irAEsEschweiler, S., Ramirez-Suastegui, C., Li, Y., King, E., Chudley, L., Thomas, J., Wood, O., von Witzleben, A., Jeffrey, D., McCann, K., Simon, H., Mondal, M., Wang, A., Dicker, M., Lopez-Guadamillas, E., Chou, T.-F., Dobbs, N.A., Essame, L., Acton, G., Kelly, F., Halbert, G., Sacco, J.J., Schache, A.G., Shaw, R., McCaul, J.A., Paterson, C., Davies, J.H., Brennan, Peter A., Singh, R.P., Loadman, Paul, Wilson, W., Hackshaw, A., Seumois, G., Okkenhaug, K., Thomas, G.J., Jones, T.M., Ay, F., Friberg, G., Kronenberg, M., Vanhaesebroeck, B., Vijayananad, P., Ottensmeier, C.H. 04 May 2022 (has links)
Yes / Phosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors
that target this PI3K have been approved for treatment of B cell malignancies1–3.
Although studies in mouse models of solid tumours have demonstrated that PI3Kδ
inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in
humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in
human patients with head and neck cancer in a neoadjuvant, double-blind,
placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ
inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and
enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses
of AMG319, immune-related adverse events (irAEs) required treatment to be
discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic
effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of
Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis
revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied
by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells,
which probably contributed to toxicity; this points towards a specific mode of action
for the emergence of irAEs. A modified treatment regimen with intermittent dosing of
PI3Kδi in mouse models led to a significant decrease in tumour growth without
inducing pathogenic T cells in colonic tissue, indicating that alternative dosing
regimens might limit toxicity. / Research Development Fund Publication Prize Award winner, May 2022.
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The versatile biomedical applications of bismuth-based nanoparticles and composites: therapeutic, diagnostic, biosensing, and regenerative propertiesShahbazi, M-A., Faghfouri, L., Ferreira, M.P.A., Figueiredo, P., Maleki, H., Sefat, Farshid, Hirvonen, J., Santos, H.A. 24 April 2020 (has links)
Yes / Studies of nanosized forms of bismuth (Bi)-containing materials have recently expanded from optical,
chemical, electronic, and engineering fields towards biomedicine, as a result of their safety, cost-effective
fabrication processes, large surface area, high stability, and high versatility in terms of shape, size, and
porosity. Bi, as a nontoxic and inexpensive diamagnetic heavy metal, has been used for the fabrication of
various nanoparticles (NPs) with unique structural, physicochemical, and compositional features to
combine various properties, such as a favourably high X-ray attenuation coefficient and near-infrared (NIR)
absorbance, excellent light-to-heat conversion efficiency, and a long circulation half-life. These features
have rendered bismuth-containing nanoparticles (BiNPs) with desirable performance for combined cancer
therapy, photothermal and radiation therapy (RT), multimodal imaging, theranostics, drug delivery,
biosensing, and tissue engineering. Bismuth oxyhalides (BiOx, where X is Cl, Br or I) and bismuth
chalcogenides, including bismuth oxide, bismuth sulfide, bismuth selenide, and bismuth telluride, have
been heavily investigated for therapeutic purposes. The pharmacokinetics of these BiNPs can be easily
improved via the facile modification of their surfaces with biocompatible polymers and proteins, resulting
in enhanced colloidal stability, extended blood circulation, and reduced toxicity. Desirable antibacterial
effects, bone regeneration potential, and tumor growth suppression under NIR laser radiation are the main
biomedical research areas involving BiNPs that have opened up a new paradigm for their future clinical
translation. This review emphasizes the synthesis and state-of-the-art progress related to the biomedical
applications of BiNPs with different structures, sizes, and compositions. Furthermore, a comprehensive
discussion focusing on challenges and future opportunities is presented. / M.-A. Shahbazi acknowledges financial support from the Academy of Finland (grant no. 317316). P. Figueiredo acknowledges the Finnish Cultural Foundation for its financial support (decision no. 00190246). H. A. Santos acknowledges financial support from the HiLIFE Research Funds, the Sigrid Juse´lius Foundation, and the Academy of Finland (grant no. 317042). / Research Development Fund Publication Prize Award winner, Jan 2020.
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Chatter model for enabling a digital twin in machiningAfazov, S., Scrimieri, Daniele 09 November 2020 (has links)
Yes / This paper presents the development of a new chatter model using measured cutting forces instead of a mathematical model with empirical nature that describes them. The utilisation of measured cutting forces enables the prediction of real-time chatter conditions and stable machining. The chatter model is validated using fast Fourier transform (FFT) analyses for detection of chatter. The key contribution of the developed chatter model is that it can be incorporated in digital twins for process monitoring and control in order to achieve greater material removal rates and improved surface quality in future industrial applications involving machining processes. / Research Development Fund Publication Prize Award winner, Sep 2020.
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