93 results on '"Emily L Williams"'
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2. Intravenous indocyanine green dye is insufficient for robust immune cell labelling in the human retina.
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Oliver H Bell, Ester Carreño, Emily L Williams, Jiahui Wu, David A Copland, Monalisa Bora, Lina Kobayter, Marcus Fruttiger, Dawn A Sim, Richard W J Lee, Andrew D Dick, and Colin J Chu
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Medicine ,Science - Abstract
It is not currently possible to reliably visualise and track immune cells in the human central nervous system or eye. Previous work demonstrated that indocyanine green (ICG) dye could label immune cells and be imaged after a delay during disease in the mouse retina. We report a pilot study investigating if ICG can similarly label immune cells within the human retina. Twelve adult participants receiving ICG angiography as part of routine standard of care were recruited. Baseline retinal images were obtained prior to ICG administration then repeated over a period ranging from 2 hours to 9 days. Matched peripheral blood samples were obtained to examine systemic immune cell labelling and activation from ICG by flow cytometry with human macrophage cultures as positive controls. Differences between the delayed near infrared ICG imaging and 488 nm autofluorescence was observed across pathologies, likely arising from the retinal pigment epithelium (RPE). Only one subject demonstrated ICG signal on peripheral blood myeloid cells and only three distinct cell-sized signals appeared over time within the retina of three participants. No significant increase in immune cell activation markers were detected after ICG administration. ICG accumulated in the endosomes of macrophage cultures and was detectable above a minimum concentration, suggesting cell labelling is possible. ICG can label RPE and may be used as an additional biomarker for RPE health across a range of retinal disorders. Standard clinical doses of intravenous ICG do not lead to robust immune cell labelling in human blood or retina and further optimisation in dose and route are required.
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- 2020
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3. The American electric utility industry’s role in promoting climate denial, doubt, and delay
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Emily L Williams, Sydney A Bartone, Emma K Swanson, and Leah C Stokes
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climate change ,climate denial ,electric utilities ,Environmental technology. Sanitary engineering ,TD1-1066 ,Environmental sciences ,GE1-350 ,Science ,Physics ,QC1-999 - Abstract
It is now well established that fossil fuel companies contributed to undermining climate science and action. In this paper, we examine the extent to which American electric utilities and affiliated organizations’ public messaging contributed to climate denial, doubt, and delay. We examined 188 documents on climate change authored by organizations in and affiliated with the utility industry from 1968 to 2019. Before 1980, electric utilities’ messaging was generally in-line with the scientific understanding of climate change. However, from 1990 to 2000, utility organizations founded and funded front groups that promoted climate doubt and denial. After 2000, these front groups were largely shut down, and utility organizations shifted to arguing for delayed action on climate change, by highlighting the responsibility of other sectors and promoting actions other than cleaning up the electricity system. Overall, our results suggest that electric utility industry organizations have promoted messaging designed to avoid taking action on reducing pollution over multiple decades. Notably, many of the utilities most engaged in communicating climate doubt and denial in the past currently have the slowest plans to decarbonize their electricity mix.
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- 2022
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4. Deceptive manipulation of competitive starting strategies influences subsequent pacing, physiological status and perceptual responses during cycling time trials
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Emily L Williams, Hollie S Jones, S Andy Sparks, David Marchant, Craig A Bridge, Adrian W Midgley, and Lars R McNaughton
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Affect ,deception ,Cycling ,pacing ,perceived exertion ,time trials ,Physiology ,QP1-981 - Abstract
Little is currently known regarding competitor influence on pacing at the start of an event and in particular the subsequent effect on the remaining distance. The purpose of the present study was to investigate the influence of starting pace on the physiological and psychological responses during cycling time trials (TT) utilising an innovative approach allowing pace to be accurately and dynamically replicated, as well as deceptively manipulated. Ten competitive male cyclists completed five 16.1 km TT, two baseline trials performed alone (BLs), and three with a simulated, dynamic avatar of which they were to match the pace of for the initial 4 km. The avatar represented either the cyclist’s fastest BL performance (NORM), 105% (FAST), or 95% (SLOW), of fastest BL performance (FBL). Physiological and psychological responses were measured every quartile of the TT. Despite manipulating a starting speed of ± 5% of fastest previous performance, there was no effect on overall 16.1 km TT performance. Manipulated starting strategies did however evoke different physiological and perceptual responses. Whole trial differences found that SLOW produced lower HR, VO2, BLa and RPE than FBL (p ≤ 0.03) and higher SE than FAST (p ≤ 0.03). Additionally, FAST had greater internal attention than NORM (p < 0.04). Over time all psychological and physiological variables had a significant condition x quartile interaction in the initial or second quartile mediated by the prescribed starting strategies. Furthermore, RPE, affect and internal attention remained elevated throughout FAST despite an attenuation in pace during self-selection of pace. There were no differences in performance time when manipulating a 16.1km cycling TT starting strategy. A slow start, encouraged greater positive perceptions, less negative physiological consequences than a faster start, and produces no impairment to performance time. It would therefore be considered an advantage in a non-drafting event, not to follow pace of fellow, superior competitors at the start of an event but perform a more negative pacing strategy, with the potential for a greater speed increase against opponents in the latter stages.
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- 2016
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5. Improvements in Cycling Time Trial Performance Are Not Sustained Following the Acute Provision of Challenging and Deceptive Feedback
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Hollie S Jones, Emily L Williams, David Marchant, S. Andy Sparks, Craig A Bridge, Adrian W Midgley, and Lars R McNaughton
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Feedback ,deception ,Cycling ,self-efficacy ,pacing ,endurance performance ,Physiology ,QP1-981 - Abstract
TThe provision of performance-related feedback during exercise is acknowledged as an influential external cue used to inform pacing decisions. The provision of this feedback in a challenging or deceptive context allows research to explore how feedback can be used to improve performance and influence perceptual responses. However, the effects of deception on both acute and residual responses have yet to be explored, despite potential application for performance enhancement. Therefore, this study investigated the effects of challenging and deceptive feedback on perceptual responses and performance in self-paced cycling time trials (TT) and explored whether changes in performance are sustained in a subsequent TT following the disclosure of the deception.Seventeen trained male cyclists were assigned to either an accurate or deceptive feedback group and performed four 16.1 km cycling TTs; 1 and 2) ride-alone baseline TTs where a fastest baseline (FBL) performance was identified, 3) a TT against a virtual avatar representing 102% of their FBL performance (PACER), and 4) a subsequent ride-alone TT (SUB). The deception group, however, were initially informed that the avatar accurately represented their FBL, but prior to SUB were correctly informed of the nature of the avatar. Affect, self-efficacy and RPE were measured every quartile. Both groups performed PACER faster than FBL and SUB (p < 0.05) and experienced lower affect (p = 0.016), lower self-efficacy (p = 0.011), and higher RPE (p < 0.001) in PACER than FBL. No significant differences were found between FBL and SUB for any variable. The presence of the pacer rather than the manipulation of performance beliefs acutely facilitates TT performance and perceptual responses. Revealing that athletes’ performance beliefs were falsely negative due to deceptive feedback provision has no effect on subsequent perceptions or performance. A single experiential exposure may not be sufficient to produce meaningful changes in the performance beliefs of trained individuals beyond the acute setting.
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- 2016
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6. Cyclophosphamide depletes tumor infiltrating T regulatory cells and combined with anti-PD-1 therapy improves survival in murine neuroblastoma
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Emily R. Webb, Julia Moreno-Vincente, Alistair Easton, Silvia Lanati, Martin Taylor, Sonya James, Emily L. Williams, Vikki English, Chris Penfold, Stephen A. Beers, and Juliet C. Gray
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Microenvironment ,Biological sciences ,Immunology ,Cancer ,Science - Abstract
Summary: The outcome for children with high-risk neuroblastoma is poor despite intensive multi-modal treatment protocols. Toxicity from current treatments is significant, and novel approaches are needed to improve outcome. Cyclophosphamide (CPM) is a key component of current chemotherapy regimens and is known to have immunomodulatory effects. However, this has not been investigated in the context of tumor infiltrating lymphocytes in neuroblastoma. Using murine models of neuroblastoma, the immunomodulatory effects of low-dose CPM were investigated using detailed immunophenotyping. We demonstrated that CPM resulted in a specific depletion of intratumoral T regulatory cells by apoptosis, and when combined with anti-PD-1 antibody therapy, this resulted in improved therapeutic efficacy. CPM combined with anti-PD-1 therapy was demonstrated to be an effective combinational therapy, with metronomic CPM found to be more effective than single dosing in more resistant tumor models. Overall, this pre-clinical data strongly support clinical evaluation of such combination strategies in neuroblastoma.
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- 2022
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7. The effectiveness of heat preparation and alleviation strategies for cognitive performance: A systematic review
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Kate J. Donnan, Emily L. Williams, and Melissa J. Bargh
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Physiology ,Physiology (medical) - Published
- 2023
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8. Figure S1 from Immunomodulatory Monoclonal Antibodies Combined with Peptide Vaccination Provide Potent Immunotherapy in an Aggressive Murine Neuroblastoma Model
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Juliet C. Gray, Martin J. Glennie, Mark S. Cragg, Peter W. Johnson, Sonya James, Stuart N. Dunn, and Emily L. Williams
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Figure S1 - PDF file 105K, Figure S1. Neuroblastoma cell lines do not express 4-1BB, CD40 or CTLA-4. The expression of 4-1BB, CD40 and CTLA-4 on naive and activated splenocytes (0.5 mg anti-CD3 i.v. 48 hr) and the neuroblastoma cell lines was determined by indirect flow cytometry. Cells were incubated with 10 microg/ml unlabelled mAb, either isotype control (Mc39/16) anti-4-1BB (LOB12.3), anti-CD40 (3/23) or anti-CTLA-4 (UC10 4F10-11) prior to washing and incubation with PE-conjugated anti-mouse Fc. Expression of 4-1BB, CD40 and CTLA-4 could be observed on T-cells from activated splenocytes, but not on naive T-cells as expected. Expression of 4-1BB, CD40 and CTLA-4 was not evident on Neuro2a, AgN2a or NXS2 cell lines. Data represents an example of three experiments
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- 2023
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9. Data from Immunomodulatory Monoclonal Antibodies Combined with Peptide Vaccination Provide Potent Immunotherapy in an Aggressive Murine Neuroblastoma Model
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Juliet C. Gray, Martin J. Glennie, Mark S. Cragg, Peter W. Johnson, Sonya James, Stuart N. Dunn, and Emily L. Williams
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Purpose: Neuroblastoma is one of the commonest extracranial tumors of childhood. The majority of patients present with metastatic disease for which outcome remains poor. Immunotherapy is an attractive therapeutic approach for this disease, and a number of neuroblastoma tumor antigens have been identified. Here, we examine the therapeutic potential of combining immunomodulatory monoclonal antibodies (mAb) with peptide vaccination in murine neuroblastoma models.Experimental Design: Neuroblastoma-bearing mice were treated with mAb targeting 4-1BB, CD40, and CTLA-4 alone, or in combination with a peptide derived from the tumor antigen survivin (GWEDPPNDI). Survivin-specific immune response and therapeutic efficacy were assessed.Results: In the Neuro2a model, treatment of established tumor with anti-4-1BB, anti-CD40, or anti-CTLA-4 mAb results in tumor regression and long-term survival in 40% to 60% of mice. This is dependent on natural killer (NK) and CD8+ T cells and is associated with tumor CD8+ lymphocyte infiltrate. Successful therapy is achieved only if mAb is given to mice once tumors are established, suggesting dependence on sufficient tumor to provide antigen. In the more aggressive AgN2a and NXS2 models, single-agent mAb therapy provides ineffective therapy. However, if mAb (anti-CTLA-4) is given in conjunction with survivin peptide vaccination, then 60% long-term survival is achieved. This is associated with the generation of survivin-specific T-cell immunity, which again is only shown in the presence of tumor antigen.Conclusions: These data suggest that the combination of antigen and costimulatory mAb may provide effective immunotherapy against neuroblastoma and may be of particular use in the minimal residual disease setting. Clin Cancer Res; 19(13); 3545–55. ©2013 AACR.
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- 2023
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10. Temporal Dynamics of Normalization Reweighting
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Daniel H. Baker, Daniela Marinova, Richard Aveyard, Lydia J. Hargreaves, Alice Renton, Ruby Castellani, Phoebe Hall, Miriam Harmens, Georgia Holroyd, Beth Nicholson, Emily L. Williams, Hannah M. Hobson, and Alex R. Wade
- Abstract
1AbstractFor decades, neural suppression in early visual cortex has been thought to be fixed. But recent work has challenged this assumption by showing that suppression can bereweightedbased on recent history; when pairs of stimuli are repeatedly presented together, suppression between them strengthens. Here we investigate the temporal dynamics of this process using a steady-state visual evoked potential (SSVEP) paradigm that provides a time-resolved, direct index of suppression between pairs of stimuli flickering at different frequencies (5 and 7Hz). Our initial analysis of an existing EEG dataset (N=100) indicated that suppression increases substantially during the first 2-5 seconds of stimulus presentation (with some variation across stimulation frequency). We then collected new EEG data (N=100) replicating this finding for both monocular and dichoptic mask arrangements in a preregistered study designed to measure reweighting. A third experiment (N=20) used source localized MEG, and found that these effects are apparent in primary visual cortex (V1), consistent with results from neurophysiological work. Because long-standing theories propose inhibition/excitation differences in autism, we also compared reweighting between individuals with high vs low autistic traits, and with and without an autism diagnosis, across our 3 data sets (total N=220). We find no compelling differences in reweighting that are associated with autism. Our results support the normalization reweighting model, and indicate that for prolonged stimulation, increases in suppression occur on the order of 2-5 seconds after stimulus onset.2Significance statementWe investigated the timecourse of a novel form of neural plasticity, normalization reweighting, using steady-state EEG in humans. We find increases in suppression during the first 2-5 seconds of stimulation, with similar dynamics for monocular and dichoptic presentation. The effects are present in primary visual cortex, and were not mediated by autistic traits. These findings demonstrate that reweighting builds up rapidly after stimulus onset, consistent with a process that adjusts the sensory response to the local environment. Normalization reweighting also has potential as a biomarker of neural function both in humans and in animal models of disease.
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- 2023
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11. Tailored forecasts can predict extreme climate informing proactive interventions in East Africa
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Chris Funk, Laura Harrison, Zewdu Segele, Todd Stuart Rosenstock, peter steward, leigh anderson, Erin Coughlan-Perez, daniel maxwell, Hussen Seid Endris, Eunice Koech, guleid artan, Fetene Teshome, Stella Aura, Gideon Galu, Diriba Korecha, weston anderson, Andrew Hoell, kerstin damerau, Emily L Williams, Aniruddha gosh, Julian Ramirez Villegas, and david Peter hughes
- Abstract
This commentary discusses new advances in the predictability of east African rains and highlights the potential for improved early warning systems (EWS), humanitarian relief efforts, and agricultural decision-making. Following an unprecedented sequence of five droughts, in 2022 23 million east Africans faced starvation, requiring >$2 billion in aid. Here, we update climate attribution studies showing that these droughts resulted from an interaction of climate change and La Niña. Then we describe, for the first time, how attribution-based insights can be combined with the latest dynamic models to predict droughts at eight-month lead-times. We then discuss behavioral and social barriers to forecast use, and review literature examining how EWS might (or might not) enhance agro-pastoral advisories and humanitarian interventions. Finally, in reference to the new World Meteorological Organization (WMO) “Early Warning for All” plan, we conclude with a set of recommendations supporting actionable and authoritative climate services. Trust, urgency, and accuracy can help overcome barriers created by limited funding, uncertain tradeoffs, and inertia. Understanding how climate change is producing predictable climate extremes now, investing in African-led EWS, and building better links between EWS and agricultural development efforts can support long-term adaptation, reducing chronic needs for billions of dollars in reactive assistance. The main messages of this commentary will be widely. Climate change is interacting with La Niña to produce extreme, but extremely predictable, Pacific sea surface temperature gradients. These gradients will affect the climate in many countries creating opportunities for prediction. Effective use of such predictions, however, will demand cross-silo collaboration.
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- 2023
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12. The effect of exercise-induced fatigue and heat exposure on soccer-specific decision-making during high-intensity intermittent exercise
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Kate J. Donnan, Emily L. Williams, and Nicholas Stanger
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Multidisciplinary - Abstract
Global warming and the globalisation of sport has increased the prevalence of sports competitions being held in hot environments. However, there is currently limited research investigating the impact of the heat on soccer-specific decision-making skills during exercise reflective of the physical demands of match-play. Therefore, the effects of heat exposure on physical and soccer-specific decision-making performance, biological markers (i.e., metanephrines), appraisal (i.e., challenge vs. threat) and affective states, during prolonged high-intensity intermittent exercise were investigated. Nine well-trained male soccer players completed a 92-min cycling intermittent sprint protocol (CISP), whilst simultaneously responding to a series of soccer-specific decision-making trials at various time points, in two temperature conditions: hot (32°C, 50%rh) and temperate (18°C, 50%rh). Results showed that decision-making score (p = .030) was impaired in the hot compared to the temperate condition. There was a reduced workload in the second half during the hot condition (p = .016), which coincided with a heightened threat state (p = .007) and more unpleasant feelings (p = .008) experienced in the hot, compared to temperate, condition. Furthermore, plasma normetanephrine (NMET) was higher at half-time (p = .012) and post-CISP (p ≤ .001). Also, plasma metanephrine (MET) was higher post-CISP (p = .009) in the hot compared to temperate condition, reflecting a heightened stress response. Our findings highlight the need for practitioners to consider the detrimental effects heat exposure can have on both physical and decision-making performance when looking to facilitate performance in hot conditions.
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- 2022
13. The Effects of Heat Exposure During Intermittent Exercise on Physical and Cognitive Performance Among Team Sport Athletes
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Kate Donnan, Emily L. Williams, and Nicholas Stanger
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Male ,medicine.medical_specialty ,Hot Temperature ,Team sport ,core temperature ,media_common.quotation_subject ,Peak power output ,Experimental and Cognitive Psychology ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,Humans ,Medicine ,Effects of sleep deprivation on cognitive performance ,Power output ,Exercise ,cognitive function ,media_common ,business.industry ,Team Sports ,030229 sport sciences ,Sensory Systems ,power output ,Sprint ,affect ,Athletes ,Physical therapy ,business ,Section III. Peak Performance ,catecholamines ,030217 neurology & neurosurgery ,Sports ,Stroop effect ,Vigilance (psychology) - Abstract
This study investigated the effects of heat exposure on physical and cognitive performance during an intermittent exercise protocol so as to reflect the incremental fatigue experienced during team sports. Twelve well-trained male team sport players completed an 80-minute cycling intermittent sprint protocol (CISP), alongside computerized vigilance and congruent (i.e., simple) and incongruent (i.e., complex) Stroop tasks of cognitive functioning, in two counterbalanced temperature conditions; hot (32°C[50%rh]) and control (18°C[50%rh]). Incongruent Stroop accuracy declined over time ( p = .002), specifically in the second ( Mdiff = –3.75, SD = 0.90%, p = .009) and third ( Mdiff = –4.58, SD = 1.22%, p = .019) quarters compared to the first quarter of the CISP; but there were no differences between temperature conditions. Congruent Stroop reaction time (RT) was quicker in the second quarter of exercise in the hot condition ( M = 561.99, SD = 112.93 ms) compared to the control condition ( M=617.80, SD = 139.71 ms; p = .022), but no differences were found for congruent Stroop accuracy nor vigilance measures. Additionally, peak power output was lower during the third quarter of the CISP in the hot condition ( M = 861.31, SD = 105.20 W) compared to the control condition ( M = 900.68, SD = 114.84 W; p diff = +616.90, SD = 306.99, p diff = +151.23, SD = 130.32, p = .002, respectively), with a marginal interaction suggesting a higher normetanephrine increase from pre- to post-CISP in the hot versus the control condition ( p = .070). Our findings suggest that accuracy for more complex decisions suffered during prolonged high-intensity intermittent exercise, perhaps due to exercise-induced catecholamine increases. Athletes may have also reduced physical effort under increased heat exposure, indicating how cognitive performance may be sustained in physically demanding environments.
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- 2020
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14. CD4+ T cells from patients with glucocorticoid-refractory immune thrombocytopenia have altered cytokine expression
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Emily L Williams, Julie Pell, Julia S. Wolf, Ian Thomas, Charlotte Bradbury, Philippa J P Lait, Rosemary Greenwood, Lauren P Schewitz-Bowers, Richard W J Lee, and Madeleine L. Stimpson
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lymphocytes ,glucocorticoids ,business.industry ,Cytokine expression ,Hematology ,Immune thrombocytopenia ,cytokines ,Refractory ,Immunology ,Biomarker (medicine) ,Medicine ,ITP ,biomarker ,business ,Glucocorticoid ,medicine.drug - Abstract
[No abstract]
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- 2022
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15. Fc-null anti-PD-1 monoclonal antibodies deliver optimal checkpoint blockade in diverse immune environments
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Julia Moreno-Vicente, Jane E Willoughby, Martin C Taylor, Steven G Booth, Vikki L English, Emily L Williams, Christine A Penfold, C Ian Mockridge, Tatyana Inzhelevskaya, Jinny Kim, H T Claude Chan, Mark S Cragg, Juliet C Gray, Stephen A Beers, Moreno-Vicente, Julia [0000-0002-1740-9350], Willoughby, Jane E [0000-0002-6326-4519], and Apollo - University of Cambridge Repository
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Pharmacology ,Cancer Research ,Immunology ,Programmed Cell Death 1 Receptor ,Antibodies, Monoclonal ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Basic Tumor Immunology ,Disease Models, Animal ,Mice ,Oncology ,Neoplasms ,Tumor Microenvironment ,Molecular Medicine ,Immunology and Allergy ,Animals ,Humans ,antibodies ,immunotherapy ,Immune Checkpoint Inhibitors ,neoplasm ,RC254-282 - Abstract
BackgroundDespite extensive clinical use, the mechanisms that lead to therapeutic resistance to anti-programmed cell-death (PD)-1 monoclonal antibodies (mAbs) remain elusive. Here, we sought to determine how interactions between the Fc region of anti-PD-1 mAbs and Fcγ receptors (FcγRs) affect therapeutic activity and how these are impacted by the immune environment.MethodsMouse and human anti-PD-1 mAbs with different Fc binding profiles were generated and characterized in vitro. The ability of these mAbs to elicit T-cell responses in vivo was first assessed in a vaccination setting using the model antigen ovalbumin. The antitumor activity of anti-PD-1 mAbs was investigated in the context of immune ‘hot’ MC38 versus ‘cold’ neuroblastoma tumor models, and flow cytometry performed to assess immune infiltration.ResultsEngagement of activating FcγRs by anti-PD-1 mAbs led to depletion of activated CD8 T cells in vitro and in vivo, abrogating therapeutic activity. Importantly, the extent of this Fc-mediated modulation was determined by the surrounding immune environment. Low FcγR-engaging mouse anti-PD-1 isotypes, which are frequently used as surrogates for human mAbs, were unable to expand ovalbumin-reactive CD8 T cells, in contrast to Fc-null mAbs. These results were recapitulated in mice expressing human FcγRs, in which clinically relevant hIgG4 anti-PD-1 led to reduced endogenous expansion of CD8 T cells compared with its engineered Fc-null counterpart. In the context of an immunologically ‘hot’ tumor however, both low-engaging and Fc-null mAbs induced long-term antitumor immunity in MC38-bearing mice. Finally, a similar anti-PD-1 isotype hierarchy was demonstrated in the less responsive ‘cold’ 9464D neuroblastoma model, where the most effective mAbs were able to delay tumor growth but could not induce long-term protection.ConclusionsOur data collectively support a critical role for Fc:FcγR interactions in inhibiting immune responses to both mouse and human anti-PD-1 mAbs, and highlight the context-dependent effect that anti-PD-1 mAb isotypes can have on T-cell responses. We propose that engineering of Fc-null anti-PD-1 mAbs would prevent FcγR-mediated resistance in vivo and allow maximal T-cell stimulation independent of the immunological environment.
- Published
- 2022
16. CD4
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Madeleine L, Stimpson, Julia S, Wolf, Emily L, Williams, Philippa J P, Lait, Lauren P, Schewitz-Bowers, Rosemary, Greenwood, Julie, Pell, Ian, Thomas, Richard W J, Lee, and Charlotte A, Bradbury
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CD4-Positive T-Lymphocytes ,Male ,Purpura, Thrombocytopenic, Idiopathic ,Cytokines ,Humans ,Female ,Prospective Studies - Published
- 2021
17. Glucocorticoid treatment in patients with newly diagnosed immune thrombocytopenia switches CD14 ++CD16 + intermediate monocytes from a pro-inflammatory to an anti-inflammatory phenotype
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Lauren P Schewitz-Bowers, Lauren V Jones, Madeleine L. Stimpson, Richard W J Lee, Philippa J P Lait, Charlotte Bradbury, Ashwin Dhanda, and Emily L Williams
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CD14 ,Inflammation ,medicine.disease_cause ,Autoimmunity ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,monocyte subsets ,immune system diseases ,hemic and lymphatic diseases ,glucorticoids ,medicine ,Interferon gamma ,business.industry ,autoimmunity ,Autoantibody ,Hematology ,humanities ,immune thrombocytopenia ,030220 oncology & carcinogenesis ,Immunology ,Interleukin 17 ,medicine.symptom ,business ,CD80 ,030215 immunology ,medicine.drug ,steroids - Abstract
Immune thrombocytopenia (ITP) is thought to result from an aberrant adaptive autoimmune response, involving autoantibodies, B and T lymphocytes, directed at platelets and megakaryocytes. Previous reports have demonstrated skewed CD4+ T-helper subset distribution and enhanced production of pro-inflammatory cytokines such as interleukin 17A and interferon gamma. The role of monocytes (MCs) in ITP is less widely described, but innate immune cells have a role in shaping CD4+ T-cell phenotypes. Glucocorticoids (GCs) are commonly used for first-line ITP treatment and modulate a broad range of immune cells including T cells and MCs. Using multiparameter flow cytometry analysis, we demonstrate the expansion of intermediate MCs (CD14++ CD16+ ) in untreated patients with newly diagnosed ITP, with these cells displaying a pro-inflammatory phenotype, characterised by enhanced expression of CD64 and CD80. After 2 weeks of prednisolone treatment (1 mg/kg daily), the proportion of intermediate MCs reduced, with enhanced expression of the anti-inflammatory markers CD206 and CD163. Healthy control MCs were distinctly different than MCs from patients with ITP before and after GC treatment. Furthermore, the GC-induced phenotype was not observed in patients with chronic ITP receiving thrombopoietin receptor agonists. These data suggest a role of MCs in ITP pathogenesis and clinical response to GC therapy.
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- 2021
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18. IL-10 and IL-17 Expression by CD4+ T Cells is Altered in Corticosteroid Refractory Immune Thrombocytopenia (ITP)
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Charlotte Bradbury, Richard W J Lee, Madeleine L. Stimpson, Philippa J P Lait, Emily L Williams, Kimberley Thirlwall, and Lauren P Schewitz-Bowers
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lymphocytes ,medicine.drug_class ,T cell ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Autoimmunity ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,hemic and lymphatic diseases ,Medicine ,Dexamethasone ,glucocorticoids ,business.industry ,autoimmunity ,Interleukin ,Hematology ,cytokines ,Interleukin 10 ,medicine.anatomical_structure ,immune thrombocytopenia ,Immunology ,Corticosteroid ,Interleukin 17 ,business ,medicine.drug - Abstract
BackgroundCorticosteroids remain the first line treatment for patients with Immune Thrombocytopenia (ITP). However, 20-30% of patients do not respond to treatment at tolerable doses. This variation in corticosteroid efficacy is replicated in other autoimmune diseases and may have an adaptive immune basis.ObjectiveTo test the hypothesis that CD4+ T cell responses to corticosteroids are different in patients with clinically defined corticosteroid refractory ITP.MethodsIn this prospective cohort study, CD4+ T cells from patients with ITP were cultured in the presence or absence of dexamethasone (Dex). Intracellular cytokine expression was then quantified by flow cytometry and compared with patients’ clinical response to corticosteroid treatment. A control cohort of patients with autoimmune uveitis was also studied to evaluate whether our findings were limited to ITP or are potentially generalizable across autoimmune diseases. ResultsThe ratio of interleukin (IL)-10 to IL-17 expression following CD4+ T cell culture with Dex was able to discriminate between ITP patients with a clinically defined complete (n=33), partial (n=12) or non-response (n=11) to corticosteroid treatment (p=0.002). These findings were replicated in patients with autoimmune uveitis (complete response n=14, non-response n=22; p=0.01) ConclusionsThere is a relative abrogation of IL-10 and persistence of IL-17 expression in the CD4+ T cells of patients who clinically fail corticosteroid therapy. This observation has potential to inform both our mechanistic understanding of the action of corticosteroids in the treatment of ITP, and as a biomarker for steroid refractory disease, with potential application across a range of haematological and non-haematological conditions.
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- 2020
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19. Glucocorticoid treatment in patients with newly diagnosed immune thrombocytopenia switches CD14
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Emily L, Williams, Madeleine L, Stimpson, Philippa J P, Lait, Lauren P, Schewitz-Bowers, Lauren V, Jones, Ashwin D, Dhanda, Richard W J, Lee, and Charlotte A, Bradbury
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Adult ,Aged, 80 and over ,Inflammation ,Male ,Purpura, Thrombocytopenic, Idiopathic ,Receptors, IgG ,Lipopolysaccharide Receptors ,Middle Aged ,Monocytes ,Young Adult ,Humans ,Female ,Glucocorticoids ,Cells, Cultured ,Aged - Abstract
Immune thrombocytopenia (ITP) is thought to result from an aberrant adaptive autoimmune response, involving autoantibodies, B and T lymphocytes, directed at platelets and megakaryocytes. Previous reports have demonstrated skewed CD4
- Published
- 2020
20. Successful Pacing Profiles of Olympic Men and Women 3,000 m Steeplechasers
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Brian Hanley and Emily L. Williams
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lcsh:Sports ,endurance ,biology ,Athletes ,Brief Research Report ,biology.organism_classification ,elite-standard athletes ,lcsh:GV557-1198.995 ,race tactics ,coaching ,Sports and Active Living ,track and field ,Energy cost ,Jump ,Psychology ,Track and field athletics ,Demography - Abstract
The presence of barriers in the steeplechase increases energy cost and makes successful pacing more difficult. This was the first study to analyze pacing profiles of successful (qualifiers for the final / Top 8 finalists) and unsuccessful (non-qualifiers / non-Top 8 finalists) Olympic steeplechasers across heats and finals, and to analyze differences between race sections (e.g., water jump vs. home straight). Finishing and section splits were collected for 75 men and 84 women competing at the 2008 and 2016 Olympic Games. Competitors were divided into groups based on finishing position (in both rounds analyzed). After a quick opening 228 m (no barriers), men who qualified for the final or finished in the Top 8 in the final had even paces for the first half with successive increases in speed in the final three laps; unsuccessful pacing profiles were more even. Successful women had mostly even paces for the whole race, and less successful athletes slowed after Lap 2. Women started the race relatively faster than men, resulting in slower second half speeds. The best men completed most race sections at the same speed, but less successful men were slower during the water jump section, suggesting less technically proficiency. Similarly, women were slower during this section, possibly because its landing dimensions are the same as for men and have a greater effect on running speed. Coaches should note the different pacing profiles adopted by successful men and women steeplechasers, and the importance of technical hurdling skills at the water jump.
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- 2020
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21. IL-10 and IL-17 expression by CD4
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Madeleine L, Stimpson, Philippa J P, Lait, Lauren P, Schewitz-Bowers, Emily L, Williams, Kimberley F, Thirlwall, Richard W J, Lee, and Charlotte A, Bradbury
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CD4-Positive T-Lymphocytes ,Purpura, Thrombocytopenic, Idiopathic ,Adrenal Cortex Hormones ,Interleukin-17 ,Humans ,Prospective Studies ,Interleukin-10 - Abstract
Corticosteroids remain the first-line treatment for patients with immune thrombocytopenia (ITP). However, 20% to 30% of patients do not respond to treatment at tolerable doses. This variation in corticosteroid efficacy is replicated in other autoimmune diseases and may have an adaptive immune basis.To test the hypothesis that CD4In this prospective cohort study, CD4The ratio of interleukin (IL)-10 to IL-17 expression following CD4There is a relative abrogation of IL-10 and persistence of IL-17 expression in the CD4
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- 2020
22. Investigating the relationship between cognitions, pacing strategies and performance in 16.1 km cycling time trials using a think aloud protocol
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Amy E. Whitehead, Remco Polman, Chris Rowley, Hollie S. Jones, David Marchant, Laura Quayle, and Emily L. Williams
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medicine.medical_specialty ,biology ,Athletes ,05 social sciences ,Future application ,Cognition ,C830 ,030229 sport sciences ,biology.organism_classification ,050105 experimental psychology ,C800 ,Developmental psychology ,C813 ,03 medical and health sciences ,0302 clinical medicine ,Time trial ,Distraction ,Physical therapy ,medicine ,0501 psychology and cognitive sciences ,Power output ,Think aloud protocol ,Psychology ,Cycling ,Applied Psychology - Abstract
Objectives\ud Three studies involved the investigation of concurrent cognitive processes and pacing behaviour during a 16.1 km cycling time trial (TT) using a novel Think Aloud (TA) protocol. Study 1 examined trained cyclist's cognitions over time whilst performing a real-life 16.1 km time trial (TT), using TA protocol. Study 2, included both trained and untrained participants who performed a 16.1 km TT in a laboratory whilst using TA. Study 3 investigated participants' experiences of using TA during a TT performance.\ud Method\ud Study 1 involved 10 trained cyclists performing a real life 16.1 km TT. Study 2 included 10 trained and 10 untrained participants who performed a laboratory-based 16.1 km TT. In both studies, all participants were asked to TA. Time, power output, speed and heart rate were measured. Verbalisations were coded into the following themes (i) internal sensory monitoring, (ii) active self-regulation, (iii) outward monitoring (iv) distraction. Cognitions and pacing strategies were compared between groups and across the duration of the TT. In study 3 all participants were interviewed post TT to explore perceptions of using TA.\ud Results\ud Study 1 and 2 found cognitions and pacing changed throughout the TT. Active self-regulation was verbalised most frequently. Differences were found between laboratory and field verbalisations and trained and untrained participants. Study 3 provided support for the use of TA in endurance research. Recommendations were provided for future application.\ud Conclusion\ud Through the use of TA this study has been able to contribute to the pacing and cycling literature and to the understanding of endurance athletes’ cognitions.
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- 2018
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23. Dietary nitrate supplementation enhances short but not longer duration running time-trial performance
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Lauren Duckworth, John P. O'Hara, Georgina Wort, Mario Siervo, Matthew Barlow, David R. Woods, Oliver M. Shannon, and Emily L. Williams
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Adult ,Male ,medicine.medical_specialty ,Physiology ,Blood Pressure ,Athletic Performance ,030204 cardiovascular system & hematology ,Work rate ,Beetroot Juice ,Running ,03 medical and health sciences ,Oxygen Consumption ,0302 clinical medicine ,Animal science ,Physiology (medical) ,Blood plasma ,Dietary Nitrate ,Exercise performance ,Humans ,Medicine ,Orthopedics and Sports Medicine ,Treadmill ,Nitrates ,business.industry ,Public Health, Environmental and Occupational Health ,030229 sport sciences ,General Medicine ,Running time ,Blood pressure ,Dietary Supplements ,Physical therapy ,Beta vulgaris ,business - Abstract
Purpose This study evaluated the effects of dietary nitrate (NO3-) supplementation on physiological functioning and exercise performance in trained runners/ triathletes conducting short and longer distance treadmill running time-trials (TT). Method Eight trained male runners or triathletes completed four exercise performance tests comprising a 10 minute warm up followed by either a 1500 m or 10,000 m treadmill TT. Exercise performance tests were preceded 3 hours before the exercise by supplementation with either 140 ml concentrated nitrate-rich (~ 12.5 mmol nitrate) (BRJ) or nitrate-deplete (~ 0.01 mmol nitrate) (PLA) beetroot juice. Results BRJ supplementation significantly elevated plasma [NO2-] (P < 0.05). Resting blood pressure and exercise V̇O2 were not significantly different between BRJ and PLA (P > 0.05). However, post-exercise blood [lactate] was significantly greater in BRJ following the 1500 m TT (6.6 ± 1.2 vs. 6.1 ± 1.5 mM; P < 0.05), but not significantly different between conditions in the 10,000 m TT (P > 0.05). Performance in the 1500 m TT was significantly faster in BRJ versus PLA (319.6 ± 36.2 vs. 325.7 ± 38.8 s; P < 0.05). Conversely, there was no significant difference in 10,000 m TT performance between conditions (2643.1 ± 324. 1 vs. 2649.9 ± 319.8 s, P > 0.05). Conclusion Acute BRJ supplementation significantly enhanced 1500 m but not 10,000 m TT performance. These findings suggest that BRJ might be ergogenic during shorter-distance TTs which allow for a high work rate, but not during longer-distance TTs, completed at a lower work rate.
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- 2017
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24. Intravenous indocyanine green dye is insufficient for robust immune cell labelling in the human retina
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Richard W J Lee, Ester Carreño, Lina Kobayter, Monalisa Bora, Jiahui Wu, Andrew D. Dick, Emily L Williams, Oliver Bell, Marcus Fruttiger, Colin J Chu, David A. Copland, and Dawn A Sim
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Male ,0301 basic medicine ,Pathology ,genetic structures ,Physiology ,Pilot Projects ,Retinal Pigment Epithelium ,Cardiovascular Medicine ,Monocytes ,Diagnostic Radiology ,White Blood Cells ,chemistry.chemical_compound ,Spectrum Analysis Techniques ,0302 clinical medicine ,Animal Cells ,Medicine and Health Sciences ,Medicine ,Prospective Studies ,Fluorescein Angiography ,Cardiovascular Imaging ,Coloring Agents ,Multidisciplinary ,medicine.diagnostic_test ,Radiology and Imaging ,Angiography ,Middle Aged ,Flow Cytometry ,Fluorescein angiography ,Body Fluids ,Blood ,medicine.anatomical_structure ,Spectrophotometry ,Injections, Intravenous ,Female ,Cytophotometry ,Cellular Types ,Anatomy ,Research Article ,Adult ,Indocyanine Green ,medicine.medical_specialty ,Retinal Disorder ,Imaging Techniques ,Immune Cells ,Ocular Anatomy ,Science ,Immunology ,Endosomes ,Research and Analysis Methods ,Retina ,Flow cytometry ,Young Adult ,03 medical and health sciences ,Immune system ,Ocular System ,Diagnostic Medicine ,Humans ,Aged ,Blood Cells ,Retinal pigment epithelium ,Staining and Labeling ,business.industry ,Macrophages ,Biology and Life Sciences ,Retinal ,Cell Biology ,eye diseases ,Autofluorescence ,030104 developmental biology ,chemistry ,Leukocytes, Mononuclear ,Feasibility Studies ,Eyes ,business ,Head ,Indocyanine green ,030217 neurology & neurosurgery - Abstract
It is not currently possible to reliably visualise and track immune cells in the human central nervous system or eye. Previous work demonstrated that indocyanine green (ICG) dye could label immune cells and be imaged after a delay during disease in the mouse retina. We report a pilot study investigating if ICG can similarly label immune cells within the human retina. Twelve adult participants receiving ICG angiography as part of routine standard of care were recruited. Baseline retinal images were obtained prior to ICG administration then repeated over a period ranging from 2 hours to 9 days. Matched peripheral blood samples were obtained to examine systemic immune cell labelling and activation from ICG by flow cytometry with human macrophage cultures as positive controls. Differences between the delayed near infrared ICG imaging and 488 nm autofluorescence was observed across pathologies, likely arising from the retinal pigment epithelium (RPE). Only one subject demonstrated ICG signal on peripheral blood myeloid cells and only three distinct cell-sized signals appeared over time within the retina of three participants. No significant increase in immune cell activation markers were detected after ICG administration. ICG accumulated in the endosomes of macrophage cultures and was detectable above a minimum concentration, suggesting cell labelling is possible. ICG can label RPE and may be used as an additional biomarker for RPE health across a range of retinal disorders. Standard clinical doses of intravenous ICG do not lead to robust immune cell labelling in human blood or retina and further optimisation in dose and route are required.
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- 2019
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25. Intermediate Monocytes in Acute Alcoholic Hepatitis Are Functionally Activated and Induce IL-17 Expression in CD4+ T Cells
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Peter Collins, Euan Yates, Richard W J Lee, Emily L Williams, Lauren P Schewitz-Bowers, Philippa J P Lait, D. Hegazy, Matthew E. Cramp, and Ashwin Dhanda
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CD4-Positive T-Lymphocytes ,Male ,CCR2 ,T cell ,CD14 ,Immunology ,T cells ,alcoholic hepatitis ,CD16 ,Lymphocyte Activation ,Monocytes ,Immunophenotyping ,Proinflammatory cytokine ,03 medical and health sciences ,0302 clinical medicine ,Liver Function Tests ,T-Lymphocyte Subsets ,TLR ,medicine ,Humans ,Immunology and Allergy ,glucocorticoids ,Hepatitis, Alcoholic ,Chemistry ,Interleukin-17 ,Memory T cell proliferation ,medicine.anatomical_structure ,Cytokines ,Female ,Disease Susceptibility ,Interleukin 17 ,Inflammation Mediators ,monocytes ,Biomarkers ,Ex vivo ,030215 immunology - Abstract
In humans, the three main circulating monocyte subsets are defined by their relative cell surface expression of CD14 and CD16. They are all challenging to study because their characteristics are strongly context specific, and this has led to a range of conflicting reports about their function, which is especially so for CD14++CD16+ (intermediate) monocytes. Ex vivo cultures are also often confounded by the concomitant use of immunosuppressive drugs. We therefore sought to characterize the phenotype and function of intermediate monocytes in the setting of acute inflammation prior to treatment in a cohort of 41 patients with acute alcoholic hepatitis (AH). Circulating intermediate monocytes were enriched in patients with AH and had an activated phenotype with enhanced expression of CCR2 and CD206 compared with healthy controls. Proinflammatory cytokine expression, including IL-1β and IL-23, was also higher than in healthy controls, but both classical (CD14++CD16−) and intermediate monocytes in AH were refractory to TLR stimulation. Compared with healthy controls, both AH monocyte subsets had greater phagocytic capacity, enhanced ability to drive memory T cell proliferation in coculture, and skewed CD4+ T cells to express an increased ratio of IL-17/IFN-γ. Furthermore, liver tissue from AH patients demonstrated an enrichment of monocytes including the intermediate subset compared with controls. These data demonstrate that intermediate monocytes are expanded, functionally activated, induce CD4+ T cell IL-17 expression, and are enriched in the liver of patients with AH.
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- 2019
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26. The effects of exercise at different temperatures on cognitive function: A systematic review
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Emily L. Williams, Kate Donnan, Nicholas Stanger, and Jade L. Morris
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medicine.medical_specialty ,05 social sciences ,Cold exposure ,Cognition ,030229 sport sciences ,050105 experimental psychology ,Experimental research ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Environmental temperature ,Post exercise ,medicine ,0501 psychology and cognitive sciences ,Cognitive skill ,Effects of sleep deprivation on cognitive performance ,Psychology ,Applied Psychology - Abstract
To date, no review has focused specifically on the potential modulating role of environmental temperature on the effects of exercise on cognitive function. Despite this, a range of occupations and performance contexts exist (e.g., military personnel, emergency services, sport) where the maintenance of cognitive function in environmentally challenging environments is crucial. Therefore, this systematic review aimed to evaluate the experimental research investigating how manipulating environmental temperature influenced the effects of acute bouts exercise on cognitive functioning from pre-to-post exercise, or during exercise. Studies to be included were assessed by two authors reviewing title, abstract, and then full-text. From the searches conducted, twenty articles were identified which met the inclusion criteria. For the purpose of this review, exercise involved in each study was categorised into low, moderate, and vigorous dosages (dependent on intensity and duration). The results indicate that moderate dosages of exercise help stimulate improved cognitive performance from pre-to-post exercise in temperate conditions, where cold exposure appears to blunt these effects. In addition, hot environments led to cognitive decrements during and post exercise which were often identified in studies that implemented prolonged moderate or vigorous exercise protocols. Therefore, suggesting a combination of heightened physiological strain from increased dose of exercise, alongside heat exposure, can be detrimental to optimal cognitive functioning, whereby executive functioning tasks appeared to be most affected. The findings from this systematic review highlight the potential modulating role of environmental temperature on the effects of exercise on cognitive function. Thus, highlighting the importance of considering the role of environmental temperature for individuals either exercising to elicit desired cognitive benefits or for those involved in physically demanding occupations or performance domains.
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- 2021
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27. Genetic Color Morphs in the Eastern Mosquitofish Experience Different Social Environments in the Wild and Laboratory
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Joseph Travis, Kimberly A. Hughes, Valerie A. Lemakos, Emily L. Williams, and Brittany Kraft
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0106 biological sciences ,0301 basic medicine ,education.field_of_study ,biology ,Ecology ,Population ,Social environment ,Gene-environment correlation ,Eastern mosquitofish ,biology.organism_classification ,010603 evolutionary biology ,01 natural sciences ,Gambusia ,Social group ,03 medical and health sciences ,030104 developmental biology ,Genetic variation ,Social partners ,Animal Science and Zoology ,education ,Ecology, Evolution, Behavior and Systematics - Abstract
The social environment of an animal is an especially interesting component of its environment because it can be shaped by both genetic and non-genetic variation among social partners. Indirect genetic effects (IGEs) are those created when genetic variation in social partners contributes to variation in an individual's phenotype; a potentially common form of IGE occurs when the expression of a behavioral phenotype depends on the particular genotypic combination of interacting individuals. Although IGEs can profoundly affect individual- and group-level fitness, population dynamics, and even community structure, understanding their importance is complicated by two inherent challenges: (1) identifying individuals with genetic differences in social interactions that can contribute to IGEs and (2) characterizing natural social interactions that potentially involve IGEs. As a first step toward addressing both these challenges in the same system, we investigated social interactions involving genetically distinct male color morphs in the poeciliid fish Gambusia holbrooki under natural and laboratory conditions. Previous work indicates that melanic (M) and silver (S) males differ in social behavior and in how conspecifics respond to them, suggesting the potential for IGEs. We used a combination of live and video recording of social groups in two natural populations and in the laboratory to determine the potential for IGEs to contribute to behavioral variation in this species. We found that M males had more social partners, and especially more female social partners than did S males, in nature and in the laboratory. These results suggest that both direct and indirect genetic effects have the potential to play a role in the expression and evolution of social behavior in G. holbrooki.
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- 2016
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28. Provider Perspectives on Partnering With Parents of Hospitalized Children to Improve Safety
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Peri Rosenfeld, Rebecca E. Rosenberg, Emily L. Williams, Beth Silber, Juliette Schlucter, Neesha Ramchandani, Susan Sullivan-Bolyai, and Gail Geraghty
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Adult ,Male ,Parents ,Pediatrics ,03 medical and health sciences ,Patient safety ,0302 clinical medicine ,Nursing ,Professional-Family Relations ,Health care ,Medicine ,Humans ,030212 general & internal medicine ,Child ,Qualitative Research ,Quality of Health Care ,business.industry ,030503 health policy & services ,Professional development ,Health services research ,General Medicine ,Focus Groups ,Focus group ,Quality Improvement ,Risk perception ,Pediatrics, Perinatology and Child Health ,Female ,Health Services Research ,Patient Safety ,Thematic analysis ,0305 other medical science ,business ,Child, Hospitalized ,Qualitative research - Abstract
BACKGROUND AND OBJECTIVES: There is increasing emphasis on the importance of patient and family engagement for improving patient safety. Our purpose in this study was to understand health care team perspectives on parent-provider safety partnerships for hospitalized US children to complement a parallel study of parent perspectives. METHODS: Our research team, including a family advisor, conducted semistructured interviews and focus groups of a purposive sample of 20 inpatient pediatric providers (nurses, patient care technicians, physicians) in an acute-care pediatric unit at a US urban tertiary hospital. We used a constant comparison technique and qualitative thematic content analysis. RESULTS: Themes emerged from providers on facilitators, barriers, and role negotiation and/or balancing interpersonal interactions in parent-provider safety partnership. Facilitators included the following: (1) mutual respect of roles, (2) parent advocacy and rule-following, and (3) provider quality care, empathetic adaptability, and transparent communication of expectations. Barriers included the following: (1) lack of respect, (2) differences in parent versus provider risk perception and parent lack of availability, and (3) provider medical errors and inconsistent communication, lack of engagement skills and time, and fear of overwhelming information. Providers described themes related to balancing parent advocacy with clinician’s expertise, a provider’s personal response to challenges to the professional role, and parents balancing relationship building with escalating safety concerns. CONCLUSIONS: To keep children safe in the hospital, providers balance perceived challenges to their personal and professional roles continuously in interpersonal interactions, paralleling parent concerns about role ambiguity and trust. Understanding these shared barriers to and facilitators of parent-provider safety partnerships can inform system design, parent education, and professional training.
- Published
- 2018
29. Presence of Spotters Improves Bench Press Performance: A Deception Study
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Andrew Sheridan, Emily L. Williams, Hollie S. Jones, Phil A. Hewitt, S. Andy Sparks, and David Marchant
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Adult ,Male ,Total work ,medicine.medical_specialty ,media_common.quotation_subject ,Physical Exertion ,Repetition maximum ,Physical Therapy, Sports Therapy and Rehabilitation ,Perceived exertion ,Bench press ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Exercise performance ,medicine ,Humans ,Orthopedics and Sports Medicine ,Body Weights and Measures ,media_common ,Resistance training ,Resistance Training ,030229 sport sciences ,General Medicine ,Deception ,Self Efficacy ,Athletes ,Physical therapy ,Perception ,Psychology ,030217 neurology & neurosurgery - Abstract
Sheridan, A, Marchant, DC, Williams, EL, Jones, HS, Hewitt, PA, and Sparks, SA. Presence of spotters improves bench press performance: a deception study. J Strength Cond Res XX(X): 000-000, 2017-Resistance exercise is a widely used method of physical training in both recreational exercise and athletic populations. The use of training partners and spotters during resistance exercise is widespread, but little is known about the effect of the presence of these individuals on exercise performance. The purpose of the current study was to investigate the effect of spotter presence on bench press performance. Twelve recreationally trained participants (age, 21.3 ± 0.8 years, height, 1.82 ± 0.1 m, and weight, 84.8 ± 11.1 kg) performed 2 trials of 3 sets to failure at 60% of 1 repetition maximum on separate occasions. The 2 trials consisted of spotters being explicitly present or hidden from view (deception). During the trials, total repetitions (reps), total weight lifted, ratings of perceived exertion (RPE), and self-efficacy were measured. Total reps and weight lifted were significantly greater with spotters (difference = 4.5 reps, t = 5.68, p < 0.001 and difference = 209.6 kg, t = 5.65, p < 0.001, respectively). Although RPE and local RPE were significantly elevated in the deception trials (difference = 0.78, f = 6.16, p = 0.030 and difference = 0.81, f = 5.89, p = 0.034, respectively), self-efficacy was significantly reduced (difference = 1.58, f = 26.90, p < 0.001). This study demonstrates that resistance exercise is improved by the presence of spotters, which is facilitated by reduced RPE and increased self-efficacy. This has important implications for athletes and clients, who should perform resistance exercise in the proximity of others, to maximize total work performed.
- Published
- 2018
30. Competitor presence reduces internal attentional focus and improves 16.1km cycling time trial performance
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Emily L. Williams, S. Andy Sparks, Adrian W. Midgley, David Marchant, Hollie S. Jones, and Lars R. Mc Naughton
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Adult ,Male ,Competitive Behavior ,medicine.medical_specialty ,Physical Exertion ,Physical Therapy, Sports Therapy and Rehabilitation ,Perceived exertion ,Athletic Performance ,Young Adult ,Time trial ,Physical medicine and rehabilitation ,Heart Rate ,Distraction ,Heart rate ,Computer Graphics ,medicine ,Humans ,Cycle ergometer ,Attention ,Orthopedics and Sports Medicine ,Power output ,Motivation ,Cross-Over Studies ,Work (physics) ,Middle Aged ,Bicycling ,Cycling ,Psychology ,human activities ,Social psychology - Abstract
Objectives: Whilst the presence of a competitor has been found to improve performance, the mechanisms influencing the change in selected work rates during direct competition have been suggested but not specifically assessed. The aim was to investigate the physiological and psychological influences of a visual avatar competitor during a 16.1-km cycling time trial performance, using trained, competitive cyclists. Design: Randomised cross-over design. Methods: Fifteen male cyclists completed four 16.1 km cycling time trials on a cycle ergometer, performing two with a visual display of themselves as a simulated avatar (FAM and SELF), one with no visual display(DO), and one with themselves and an opponent as simulated avatars (COMP). Participants were informed the competitive avatar was a similar ability cyclist but it was actually a representation of their fastest previous performance. Results: Increased performance times were evident during COMP (27.8 ± 2.0 min) compared to SELF(28.7 ± 1.9 min) and DO (28.4 ± 2.3 min). Greater power output, speed and heart rate were apparent during COMP trial than SELF (p < 0.05) and DO (p ≤ 0.06). There were no differences between SELF and DO.Ratings of perceived exertion were unchanged across all conditions. Internal attentional focus was significantly reduced during COMP trial (p < 0.05), suggesting reduced focused on internal sensations during an increase in performance. Conclusions: Competitive cyclists performed significantly faster during a 16.1-km competitive trial than when performing maximally, without a competitor. The improvement in performance was elicited due to a greater external distraction, deterring perceived exertion.
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- 2015
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31. CD14++CD16+ Monocytes Are Enriched by Glucocorticoid Treatment and Are Functionally Attenuated in Driving Effector T Cell Responses
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Susan Hannes, Ping Chen, Fernando Martinez Estrada, Ashwin Dhanda, Sima Hirani, Robert B. Nussenblatt, Diamond Ling, Jennifer Dailey, Zhiyu Li, Han Si, Emily L Williams, William R Tucker, Baoying Liu, Shayma Jawad, H. Nida Sen, Jason L Chien, Ian Thompson, Siamon Gordon, Amol Sura, Megan Casady, Lai Wei, and Richard W J Lee
- Subjects
T cell ,CD14 ,Immunology ,Lipopolysaccharide Receptors ,Autoimmunity ,chemical and pharmacologic phenomena ,CD16 ,GPI-Linked Proteins ,Lymphocyte Activation ,T-Lymphocytes, Regulatory ,Article ,Dexamethasone ,Autoimmune Diseases ,Uveitis ,Interferon-gamma ,medicine ,Humans ,Immunology and Allergy ,Interferon gamma ,Glucocorticoids ,Cells, Cultured ,Cell Proliferation ,Chemistry ,Monocyte ,Interleukin-17 ,Receptors, IgG ,Cell Differentiation ,hemic and immune systems ,Th1 Cells ,Molecular biology ,Interleukin-10 ,Interleukin 10 ,medicine.anatomical_structure ,Leukocytes, Mononuclear ,Interleukin 17 ,Glucocorticoid ,medicine.drug - Abstract
Human peripheral monocytes have been categorized into three subsets based on differential expression levels of CD14 and CD16. However, the factors that influence the distribution of monocyte subsets and the roles that each subset plays in autoimmunity are not well studied. In this study, we show that circulating monocytes from patients with autoimmune uveitis exhibit a skewed phenotype toward intermediate CD14++CD16+ cells, and that this is associated with glucocorticoid therapy. We further demonstrate that CD14++CD16+ monocytes from patients and healthy control donors share a similar cell-surface marker and gene expression profile. Comparison of the effects of intermediate CD14++CD16+ monocytes with classical CD14++CD16− and nonclassical CD14+CD16++ monocytes revealed that the intermediate CD14++CD16+ subset had an attenuated capacity to promote both naive CD4+ T cell proliferation and polarization into a Th1 phenotype, and memory CD4+ T cell proliferation and IL-17 expression. Furthermore, CD14++CD16+ cells inhibit CD4+ T cell proliferation induced by other monocyte subsets and enhance CD4+ T regulatory cell IL-10 expression. These data demonstrate the impact of glucocorticoids on monocyte phenotype in the context of autoimmune disease and the differential effects of monocyte subsets on effector T cell responses.
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- 2015
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32. Information acquisition differences between experienced and novice time trial cyclists
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Florentina J. Hettinga, Andrew Sparks, Craig A. Bridge, Hollie S. Jones, Lars R. McNaughton, Emily L. Williams, Paul Ellison, Dominic Micklewright, David Parry, David Marchant, Tom Foulsham, and Manhal Boya
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Adult ,Male ,medicine.medical_specialty ,Eye Movements ,Feedback, Psychological ,Physical Exertion ,Physical Therapy, Sports Therapy and Rehabilitation ,Athletic Performance ,C832 ,050105 experimental psychology ,C855 ,03 medical and health sciences ,A900 ,0302 clinical medicine ,Time trial ,Frequent periods ,Physical medicine and rehabilitation ,Heart Rate ,Task Performance and Analysis ,medicine ,Humans ,0501 psychology and cognitive sciences ,Orthopedics and Sports Medicine ,Power output ,Information acquisition ,05 social sciences ,Heart rate monitor ,Cognition ,030229 sport sciences ,C600 ,Bicycling ,C800 ,C813 ,Eye tracking ,Perception ,Psychology ,Cadence - Abstract
Purpose: To use eye-tracking technology to directly compare information acquisition behavior of experienced and novice cyclists during a self-paced 10 mile (16.1 km) time-trial. Method: Two groupsof novice (N=10) and experienced cyclists (N=10) performed a 10-mile self-paced time-trial (TT) on two separate occasions during which a number of feedback variables (speed, distance, power output, cadence, heart rate, and time) were projected within their view. A large RPE scale was also presented next to the projected information and participants. Participants were fitted with a headmounted eye tracker and heart rate monitor. Results: Experienced cyclists performed both time-trials quicker than novices (F1,18=6.8, P=.018) during which they primarily looked at speed (9 of 10 participants) whereas novices primarily looked at distance (6 of 10 participants). Experienced cyclists looked at primary information for longer than novices across the whole time-trial (24.5±4.2% vs. 34.2±6.1%, t18=4.2, P
- Published
- 2017
33. Effects of Dietary Nitrate Supplementation on Physiological Responses, Cognitive Function, and Exercise Performance at Moderate and Very-High Simulated Altitude
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Oliver M. Shannon, Lauren Duckworth, Matthew J. Barlow, Kevin Deighton, Jamie Matu, Emily L. Williams, David Woods, Long Xie, Blossom C. M. Stephan, Mario Siervo, and John P. O'Hara
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beetroot juice ,lcsh:QP1-981 ,nitrate ,nitric oxide ,exercise performance ,lcsh:Physiology ,altitude - Abstract
Purpose: Nitric oxide (NO) bioavailability is reduced during acute altitude exposure, contributing toward the decline in physiological and cognitive function in this environment. This study evaluated the effects of nitrate (NO3−) supplementation on NO bioavailability, physiological and cognitive function, and exercise performance at moderate and very-high simulated altitude.Methods:Ten males (mean (SD): V˙O2max: 60.9 (10.1) ml·kg−1·min−1) rested and performed exercise twice at moderate (~14.0% O2; ~3,000 m) and twice at very-high (~11.7% O2; ~4,300 m) simulated altitude. Participants ingested either 140 ml concentrated NO3−-rich (BRJ; ~12.5 mmol NO3−) or NO3−-deplete (PLA; 0.01 mmol NO3−) beetroot juice 2 h before each trial. Participants rested for 45 min in normobaric hypoxia prior to completing an exercise task. Exercise comprised a 45 min walk at 30% V˙O2max and a 3 km time-trial (TT), both conducted on a treadmill at a 10% gradient whilst carrying a 10 kg backpack to simulate altitude hiking. Plasma nitrite concentration ([NO2−]), peripheral oxygen saturation (SpO2), pulmonary oxygen uptake (V˙O2), muscle and cerebral oxygenation, and cognitive function were measured throughout.Results: Pre-exercise plasma [NO2−] was significantly elevated in BRJ compared with PLA (p = 0.001). Pulmonary V˙O2 was reduced (p = 0.020), and SpO2 was elevated (p = 0.005) during steady-state exercise in BRJ compared with PLA, with similar effects at both altitudes. BRJ supplementation enhanced 3 km TT performance relative to PLA by 3.8% [1,653.9 (261.3) vs. 1718.7 (213.0) s] and 4.2% [1,809.8 (262.0) vs. 1,889.1 (203.9) s] at 3,000 and 4,300 m, respectively (p = 0.019). Oxygenation of the gastrocnemius was elevated during the TT consequent to BRJ (p = 0.011). The number of false alarms during the Rapid Visual Information Processing Task tended to be lower with BRJ compared with PLA prior to altitude exposure (p = 0.056). Performance in all other cognitive tasks did not differ significantly between BRJ and PLA at any measurement point (p ≥ 0.141).Conclusion: This study suggests that BRJ improves physiological function and exercise performance, but not cognitive function, at simulated moderate and very-high altitude.
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- 2017
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34. To align or not to align? Research methods and its relationship with dissertation marks across sport undergraduate degree programmes within a UK-based HE institution
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Hollie S. Jones, Richard Michael Page, Laura Houghton, John Bostock, and Emily L. Williams
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Medical education ,Higher education ,business.industry ,media_common.quotation_subject ,05 social sciences ,050301 education ,Constructive alignment ,Variance (accounting) ,01 natural sciences ,Degree (music) ,Education ,010104 statistics & probability ,Tourism, Leisure and Hospitality Management ,Pedagogy ,Institution ,X342 ,X200 ,0101 mathematics ,business ,Psychology ,0503 education ,Curriculum ,media_common - Abstract
Much research has referred to the complexity of research methods modules within undergraduate degree programmes. Less attention has been paid to the objective understanding of alignment between research methods and final year dissertations. This study explored relationships across Sport and Exercise Science (SES) and Sports Therapy (ST) programmes within a UK-based Higher Education institution. Analysis revealed females (N=73) outperformed males (N=117) at Levels 4/5, and SES students outperformed ST at Level 6. The Level 5 statistics assessment explained the lowest variance in the dissertation, suggesting poor alignment in curriculum design. Future research should consider the efficacy of statistics-based modules.
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- 2017
35. Changes in cognition over a 16.1 km cycling time trial using Think Aloud protocol : preliminary evidence
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Emily L. Williams, Remco Polman, Jamie Taylor, Hollie S. Jones, Amy E. Whitehead, Christopher Dowling, and David Morley
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Data collection ,Social Psychology ,biology ,Athletes ,05 social sciences ,Applied psychology ,Protocol analysis ,Cognition ,030229 sport sciences ,biology.organism_classification ,050105 experimental psychology ,Developmental psychology ,C800 ,RC1200 ,03 medical and health sciences ,C813 ,0302 clinical medicine ,Time trial ,Quartile ,0501 psychology and cognitive sciences ,Observational study ,Think aloud protocol ,Psychology ,Applied Psychology - Abstract
Objectives: This study investigated cognitions of cyclists during a competitive time trial (TT) event using Think Aloud (TA) protocol analysis. Design: Single group, observational design. Method: Fifteen male and three female cyclists from the North West of England verbalised their thoughts throughout an outdoor competitive 16.1 km cycling time trial (Level 2 TA). Verbalisations were recorded using iVue Horizon 1080P camera glasses. Data was transcribed verbatim, analysed using deductive content analysis and grouped into themes: (i) Pain And Discomfort (Fatigue, Pain), (ii) External Feedback (Time, Speed, Heart Rate), (iii) Environment (Surroundings, Traffic and Other Cyclists), (iv) Pace and Distance (Pace, Distance). The number of verbalisations within each theme were analysed by distance quartile using Friedman tests to examine changes in cognitions over time. Results: Associative themes, including Fatigue and Pain, were verbalised more frequently in the earlier stages of the TT and less in the final quartile, whereas verbalisations about Distance significantly increased in the last quartile. Conclusions: This study demonstrates how a novel data collection method can capture in-event cognitions of endurance athletes. It provides an important extension to previous literature, showing how individuals may process and attend to information over time during an exercise bout. Future research should establish the relationship between performance and cognitive processes.
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- 2017
36. Deception Studies Manipulating Centrally Acting Performance Modifiers
- Author
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Sandy Sparks, Emily L. Williams, Lars R. McNaughton, Dominic Micklewright, David Marchant, and Hollie S. Jones
- Subjects
Feedback, Physiological ,Competitive Behavior ,Motivation ,Deception ,Time Factors ,End point ,Computer science ,media_common.quotation_subject ,Physical Exertion ,Feed forward ,Brain ,Physical Therapy, Sports Therapy and Rehabilitation ,Athletic Performance ,Task (project management) ,Humans ,Perception ,Orthopedics and Sports Medicine ,Set (psychology) ,Exercise ,media_common ,Cognitive psychology - Abstract
Athletes anticipatorily set and continuously adjust pacing strategies before and during events to produce optimal performance. Self-regulation ensures maximal effort is exerted in correspondence with the end point of exercise, while preventing physiological changes that are detrimental and disruptive to homeostatic control. The integration of feedforward and feedback information, together with the proposed brain's performance modifiers is said to be fundamental to this anticipatory and continuous regulation of exercise. The manipulation of central, regulatory internal and external stimuli has been a key focus within deception research, attempting to influence the self-regulation of exercise and induce improvements in performance. Methods of manipulating performance modifiers such as unknown task end point, deceived duration or intensity feedback, self-belief, or previous experience create a challenge within research, as although they contextualize theoretical propositions, there are few ecological and practical approaches which integrate theory with practice. In addition, the different methods and measures demonstrated in manipulation studies have produced inconsistent results. This review examines and critically evaluates the current methods of how specific centrally controlled performance modifiers have been manipulated, within previous deception studies. From the 31 studies reviewed, 10 reported positive effects on performance, encouraging future investigations to explore the mechanisms responsible for influencing pacing and consequently how deceptive approaches can further facilitate performance. The review acts to discuss the use of expectation manipulation not only to examine which methods of deception are successful in facilitating performance but also to understand further the key components used in the regulation of exercise and performance.
- Published
- 2014
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37. Physiological and Psychological Effects of Deception on Pacing Strategy and Performance: A Review
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Emily L. Williams, Hollie S. Jones, Lars R. Mc Naughton, Craig A. Bridge, Dominic Micklewright, Adrian W. Midgley, and Dave Marchant
- Subjects
Deception ,medicine.medical_treatment ,media_common.quotation_subject ,Control (management) ,Psychological intervention ,Physical Therapy, Sports Therapy and Rehabilitation ,Athletic Performance ,Biofeedback ,Critical appraisal ,Presentation ,medicine ,Humans ,Orthopedics and Sports Medicine ,Energy Metabolism ,Psychology ,Exercise ,Fatigue ,Sports ,Research evidence ,Cognitive psychology ,Pace ,media_common - Abstract
The aim of an optimal pacing strategy during exercise is to enhance performance whilst ensuring physiological limits are not surpassed, which has been shown to result in a metabolic reserve at the end of the exercise. There has been debate surrounding the theoretical models that have been proposed to explain how pace is regulated, with more recent research investigating a central control of exercise regulation. Deception has recently emerged as a common, practical approach to manipulate key variables during exercise. There are a number of ways in which deception interventions have been designed, each intending to gain particular insights into pacing behaviour and performance. Deception methodologies can be conceptualised according to a number of dimensions such as deception timing (prior to or during exercise), presentation frequency (blind, discontinuous or continuous) and type of deception (performance, biofeedback or environmental feedback). However, research evidence on the effects of deception has been perplexing and the use of complex designs and varied methodologies makes it difficult to draw any definitive conclusions about how pacing strategy and performance are affected by deception. This review examines existing research in the area of deception and pacing strategies, and provides a critical appraisal of the different methodological approaches used to date. It is hoped that this analysis will inform the direction and methodology of future investigations in this area by addressing the mechanisms through which deception impacts upon performance and by elucidating the potential application of deception techniques in training and competitive settings.
- Published
- 2013
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- View/download PDF
38. Transposable elements occur more frequently in autism-risk genes: Implications for the role of genomic instability in autism
- Author
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Manuel F. Casanova, Mengsheng Qiu, Andrew E. Switala, Emily L. Williams, and Hong Li
- Subjects
Transposable element ,Genome instability ,Genetics ,General Neuroscience ,medicine ,Autism ,Epigenetics of autism ,Biology ,medicine.disease ,Gene ,Sequence (medicine) - Abstract
An extremely large number of genes have been associated with autism. The functions of these genes span numerous domains and prove challenging in the search for commonalities underlying the conditions. In this study, we instead looked at characteristics of the genes themselves, specifically in the nature of their transposable element content. Utilizing available sequence databases, we compared occurrence of transposons in autismrisk genes to randomized controls and found that transposable content was significantly greater in our autism group. These results suggest a relationship between transposable element content and autism-risk genes and have implications for the stability of those genomic regions.
- Published
- 2013
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39. Sodium bicarbonate ingestion and individual variability in time-to-peak pH
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Peter Miller, Lars R. Mc Naughton, Emily L. Williams, Craig A. Bridge, Andy Sparks, David J. Bentley, and Amy L. Robinson
- Subjects
Adult ,Male ,Coefficient of variation ,Administration, Oral ,030209 endocrinology & metabolism ,Physical Therapy, Sports Therapy and Rehabilitation ,Performance-Enhancing Substances ,Athletic Performance ,Buffers ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Animal science ,medicine ,Ingestion ,Humans ,Orthopedics and Sports Medicine ,Acidosis ,Acid-Base Equilibrium ,Sodium bicarbonate ,030229 sport sciences ,Hydrogen-Ion Concentration ,Sodium Bicarbonate ,chemistry ,Time to peak ,Acid–base reaction ,medicine.symptom ,Blood ph - Abstract
This study determined variability in time-to-peak pH after consumption of 300 mg kg-1 of sodium bicarbonate. Seventeen participants (mean ± SD: age 21.38 ± 1.5 years; mass 75.8 ± 5.8 kg; height 176.8 ± 7.6 cm) reported to the laboratory where a resting capillary sample was taken. Then, 300 mg kg-1 of NaHCO3 in 450 ml of flavoured water was ingested. Participants rested for 90 min and repeated blood samples were procured at 10 min intervals for 60 min and then every 5 min until 90 min. Blood pH concentrations were measured. Results suggested that time-to-peak pH (64.41 ± 18.78 min) was variable with a range of 10-85 min and a coefficient of variation of 29.16%. A bimodal distribution occurred, at 65 and 75 min. In conclusion, athletes, when using NaHCO3 as an ergogenic aid, should determine their time-to-peak pH to best utilize the added buffering capacity this substance allows.
- Published
- 2016
40. Deceptive Manipulation of Competitive Starting Strategies Influences Subsequent Pacing, Physiological Status, and Perceptual Responses during Cycling Time Trials
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S. Andy Sparks, Hollie S. Jones, Lars R. McNaughton, Adrian W. Midgley, David Marchant, Emily L. Williams, and Craig A. Bridge
- Subjects
medicine.medical_specialty ,Physiology ,media_common.quotation_subject ,time trials ,Positive perception ,Affect (psychology) ,lcsh:Physiology ,deception ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Physiology (medical) ,Perception ,medicine ,030212 general & internal medicine ,Power output ,Simulation ,Original Research ,Pace ,media_common ,perceived exertion ,pacing ,lcsh:QP1-981 ,Cycling ,030229 sport sciences ,Affect ,C813 ,power output ,Quartile ,Slow-start ,Psychology ,self-efficacy - Abstract
Little is currently known regarding competitor influence on pacing at the start of an event and in particular the subsequent effect on the remaining distance. The purpose of the present study was to investigate the influence of starting pace on the physiological and psychological responses during cycling time trials (TT) utilizing an innovative approach allowing pace to be accurately and dynamically replicated, as well as deceptively manipulated. Ten competitive male cyclists completed five 16.1 km TT, two baseline trials performed alone (BLs), and three with a simulated, dynamic avatar of which they were to match the pace of for the initial 4 km. The avatar represented either the cyclist's fastest BL performance (NORM), 105% (FAST), or 95% (SLOW), of fastest BL performance (FBL). Physiological and psychological responses were measured every quartile of the TT. Despite manipulating a starting speed of ± 5% of fastest previous performance, there was no effect on overall 16.1 km TT performance. Manipulated starting strategies did however evoke different physiological and perceptual responses. Whole trial differences found that SLOW produced lower HR, VO2, BLa and RPE than FBL (p ≤ 0.03) and higher SE than FAST (p ≤ 0.03). Additionally, FAST had greater internal attention than NORM (p < 0.04). Over time all psychological and physiological variables had a significant condition × quartile interaction in the initial or second quartile mediated by the prescribed starting strategies. Furthermore, RPE, affect, and internal attention remained elevated throughout FAST despite an attenuation in pace during self-selection of pace. There were no differences in performance time when manipulating a 16.1 km cycling TT starting strategy. A slow start, encouraged greater positive perceptions, and less negative physiological consequences than a faster start, and produces no impairment to performance time. It would therefore be considered an advantage in a non-drafting event, not to follow pace of fellow, superior competitors at the start of an event but perform a more negative pacing strategy, with the potential for a greater speed increase against opponents in the latter stages.
- Published
- 2016
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41. Improvements in Cycling Time Trial Performance Are Not Sustained Following the Acute Provision of Challenging and Deceptive Feedback
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S. Andy Sparks, Adrian W. Midgley, Hollie S. Jones, Lars R. Mc Naughton, David Marchant, Emily L. Williams, and Craig A. Bridge
- Subjects
medicine.medical_specialty ,Physiology ,media_common.quotation_subject ,C850 ,Context (language use) ,Audiology ,Affect (psychology) ,C832 ,endurance performance ,050105 experimental psychology ,lcsh:Physiology ,Feedback ,deception ,03 medical and health sciences ,0302 clinical medicine ,Time trial ,Physiology (medical) ,Perception ,medicine ,0501 psychology and cognitive sciences ,previous performance ,Simulation ,media_common ,Self-efficacy ,pacing ,biology ,lcsh:QP1-981 ,Athletes ,05 social sciences ,Cycling ,030229 sport sciences ,Deception ,biology.organism_classification ,C800 ,C813 ,Quartile ,Psychology ,self-efficacy - Abstract
The provision of performance-related feedback during exercise is acknowledged as an influential external cue used to inform pacing decisions. The provision of this feedback in a challenging or deceptive context allows research to explore how feedback can be used to improve performance and influence perceptual responses. However, the effects of deception on both acute and residual responses have yet to be explored, despite potential application for performance enhancement. Therefore, this study investigated the effects of challenging and deceptive feedback on perceptual responses and performance in self-paced cycling time trials (TT) and explored whether changes in performance are sustained in a subsequent TT following the disclosure of the deception.\ud \ud Seventeen trained male cyclists were assigned to either an accurate or deceptive feedback group and performed four 16.1 km cycling TTs; 1 and 2) ride-alone baseline TTs where a fastest baseline (FBL) performance was identified, 3) a TT against a virtual avatar representing 102% of their FBL performance (PACER), and 4) a subsequent ride-alone TT (SUB). The deception group, however, were initially informed that the avatar accurately represented their FBL, but prior to SUB were correctly informed of the nature of the avatar. Affect, self-efficacy and RPE were measured every quartile.\ud \ud Both groups performed PACER faster than FBL and SUB (p < 0.05) and experienced lower affect (p = 0.016), lower self-efficacy (p = 0.011), and higher RPE (p < 0.001) in PACER than FBL. No significant differences were found between FBL and SUB for any variable.\ud \ud The presence of the pacer rather than the manipulation of performance beliefs acutely facilitates TT performance and perceptual responses. Revealing that athletes’ performance beliefs were falsely negative due to deceptive feedback provision has no effect on subsequent perceptions or performance. A single experiential exposure may not be sufficient to produce meaningful changes in the performance beliefs of trained individuals beyond the acute setting.
- Published
- 2016
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42. Parents' Perspectives on 'Keeping Their Children Safe' in the Hospital
- Author
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Peri Rosenfeld, Gail Geraghty, Rebecca E. Rosenberg, Stella Deng, Beth Silber, Susan Sullivan-Bolyai, Juliette Schlucter, and Emily L. Williams
- Subjects
Male ,Parents ,MEDLINE ,Interpersonal communication ,Staff education ,Pediatrics ,03 medical and health sciences ,Patient safety ,0302 clinical medicine ,Nursing ,Medicine ,Humans ,030212 general & internal medicine ,Hospital ward ,Child ,General Nursing ,Qualitative Research ,030504 nursing ,business.industry ,medicine.disease ,Hospitals ,Content analysis ,General partnership ,Child, Preschool ,Female ,Perception ,Medical emergency ,Patient Safety ,0305 other medical science ,business ,Child, Hospitalized ,Qualitative research - Abstract
This study explored parents' perspectives regarding their involvement in safety for their hospitalized children. We employed qualitative description and semistructured interviews of parents of children in an urban tertiary hospital ward. Content analysis revealed 4 parent themes: risks to child safety and comfort, hospital role as a protector, participation in safety varies by individual and organizational factors, and balancing safety with "speaking up" interpersonal risks. We suggest key concepts to incorporate into staff education and family engagement/safety programs to develop effective partnerships between clinicians and parents.
- Published
- 2016
43. Ingestion of a Nitric Oxide Enhancing Supplement Improves Resistance Exercise Performance
- Author
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Scott L Mosher, S. Andy Sparks, David J. Bentley, Emily L. Williams, and Lars R. Mc Naughton
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Physical Therapy, Sports Therapy and Rehabilitation ,Athletic Performance ,Placebo ,Bench press ,law.invention ,Nitric oxide ,Beverages ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,0302 clinical medicine ,Animal science ,Randomized controlled trial ,Nitrate ,Double-Blind Method ,law ,Medicine ,Ingestion ,Humans ,Orthopedics and Sports Medicine ,Lactic Acid ,030109 nutrition & dietetics ,Cross-Over Studies ,Nitrates ,business.industry ,Resistance training ,Resistance Training ,030229 sport sciences ,General Medicine ,Crossover study ,chemistry ,Dietary Supplements ,Physical therapy ,Physical Endurance ,Beta vulgaris ,business - Abstract
Mosher, SL, Sparks, SA, Williams, EL, Bentley, DJ, and Mc Naughton, LR. Ingestion of a nitric oxide enhancing supplement improves resistance exercise performance. J Strength Cond Res 30 (12): 3520-3524, 2016-Studies have established that supplementation of nitrate increases nitric oxide which in turn improves exercise performance. The current study aimed to investigate the effects of nitrate ingestion on performance of bench press resistance exercise until failure. Twelve recreationally active (age, 21 ± 2 years, height, 177.2 ± 4.0 cm, weight, 82.49 ± 9.78 kg) resistance-trained men participated in the study. The study used a double-blind, randomized cross-over design, where participants ingested either 70 ml of "BEET It Sport" nitrate shot containing 6.4 millimoles (mmol·L) or 400 mg of nitrate or a blackcurrant placebo drink. Participants completed a resistance exercise session, consisting of bench press exercise at an intensity of 60% of their established 1 repetition maximum (1RM), for 3 sets until failure with 2 minutes rest interval between sets. The repetitions completed, total weight lifted, local and general rate of perceived exertion (RPE), and blood lactate were all measured. The results showed a significant difference in repetitions to failure (p ≤ 0.001) and total weight lifted (p ≤ 0.001). However, there were no significant difference between blood lactate over the 2 trials (p = 0.238), and no difference in Local (p = 0.807) or general (p = 0.420) indicators of fatigue as measured by RPE. This study demonstrates that nitrate supplementation has the potential to improve resistance training performance and work output compared with a placebo.
- Published
- 2016
44. Development and characterisation of monoclonal antibodies specific for the murine inhibitory FcγRIIB (CD32B)
- Author
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Christine A. Penfold, Mark S. Cragg, Betty Lau, H.T. Claude Chan, C. Ian Mockridge, Ali Roghanian, Emily L Williams, Alison L. Tutt, Kerry L. Cox, J. Sjef Verbeek, Ruth R. French, and Martin J. Glennie
- Subjects
CD32 ,biology ,medicine.drug_class ,medicine.medical_treatment ,Immunology ,Immunotherapy ,CD16 ,Monoclonal antibody ,Immune system ,biology.protein ,medicine ,Immunology and Allergy ,Avidity ,Antibody ,Receptor - Abstract
Fc receptors (FcRs) play a key role in regulating and coordinating responses from both innate and adaptive arms of the immune system. The inhibitory Fc gamma receptor II (FcγRIIB; CD32) is central to this regulation with FcγRIIB−/− mice demonstrating augmented responses to mAb immunotherapy, elevated incidence and severity of auto-immunity, and increased response to mAb-mediated cancer therapy. To date, these observations have remained unexploited therapeutically, partly through a lack of specific mAb reagents capable of exclusively binding mouse FcγRIIB. Thus almost all of the FcγRIIB-binding mAb currently available, such as 2.4G2, also bind FcγRIII (CD16), and polyclonal reagents have limited availability and are of unproven specificity and avidity, making in vivo manipulation of FcγRIIB impossible. Following an extensive immunisation protocol using FcγRIIB−/− mice, we recently produced three unique mAb that are suitable for this purpose. Here we characterise these novel reagents and demonstrate that they fall into two distinct categories; those which cause phosphorylation and subsequent activation of FcγRIIB (agonistic) and those that block receptor phosphorylation (antagonistic). These two types of mAb exhibit different characteristics in a range of biochemical, cellular, and functional assays relevant to FcγRIIB activity and mAb therapy.
- Published
- 2012
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45. Fc gamma receptor IIb on target B cells promotes rituximab internalization and reduces clinical efficacy
- Author
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Sean H. Lim, Kerry L. Cox, Ruth R. French, Kathleen N. Potter, H.T. Claude Chan, Stephen A. Beers, Martin J. Glennie, Emily L Williams, Peter Johnson, Andrew Davies, Andrew T M Vaughan, C. Ian Mockridge, Sandra V. Dixon, Mark S. Cragg, Margaret Ashton-Key, and David Oscier
- Subjects
Lymphoma, B-Cell ,Antibodies, Neoplasm ,Recombinant Fusion Proteins ,media_common.quotation_subject ,Chronic lymphocytic leukemia ,education ,Immunology ,Antigen-Antibody Complex ,Lymphoma, Mantle-Cell ,Biology ,Transfection ,Biochemistry ,Antibodies, Monoclonal, Murine-Derived ,Phagocytosis ,Antigens, Neoplasm ,immune system diseases ,Cell Line, Tumor ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Phosphorylation ,Internalization ,B cell ,media_common ,CD20 ,B-Lymphocytes ,Macrophages ,Receptors, IgG ,Cell Biology ,Hematology ,Antigens, CD20 ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Endocytosis ,Leukemia ,Treatment Outcome ,medicine.anatomical_structure ,Drug Resistance, Neoplasm ,biology.protein ,Mantle cell lymphoma ,Rituximab ,Lysosomes ,Protein Processing, Post-Translational ,Biomarkers ,medicine.drug - Abstract
The anti-CD20 mAb rituximab is central to the treatment of B-cell malignancies, but resistance remains a significant problem. We recently reported that resistance could be explained, in part, by internalization of rituximab (type I anti-CD20) from the surface of certain B-cell malignancies, thus limiting engagement of natural effectors and increasing mAb consumption. Internalization of rituximab was most evident in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), but the extent of internalization was heterogeneous within each disease. Here, we show that the inhibitory FcγRIIb on target B cells promotes this process and is largely responsible for the observed heterogeneity across a range of B-cell malignancies. Internalization correlated strongly with FcγRIIb expression on normal and malignant B cells, and resulted in reduced macrophage phagocytosis of mAb-coated targets. Furthermore, transfection of FcγRIIb into FcγRIIb negative Ramos cells increased internalization of rituximab in a dose-dependent manner. Target-cell FcγRIIb promoted rituximab internalization in a cis fashion and was independent of FcγRIIb on neighboring cells. It became phosphorylated and internalized along with CD20:anti-CD20 complexes before lysosomal degradation. In MCL patients, high FcγRIIb expression predicted less durable responses after rituximab-containing regimens. Therefore, target-cell FcγRIIb provides a potential biomarker of response to type I anti-CD20 mAb.
- Published
- 2011
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46. Quantitative analysis of the shape of the corpus callosum in patients with autism and comparison individuals
- Author
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Andrew E. Switala, Diane L. Williams, Ahmed Elnakib, Ayman El-Baz, Emily L. Williams, Manuel F. Casanova, Nancy J. Minshew, and Thomas E. Conturo
- Subjects
Intelligence quotient ,Splenium ,Anatomy ,Commissure ,medicine.disease ,Corpus callosum ,Brain mapping ,mental disorders ,Developmental and Educational Psychology ,medicine ,Autism ,In patient ,Abnormality ,Psychology ,Neuroscience - Abstract
Multiple studies suggest that the corpus callosum in patients with autism is reduced in size. This study attempts to elucidate the nature of this morphometric abnormality by analyzing the shape of this structure in 17 high-functioning patients with autism and an equal number of comparison participants matched for age, sex, IQ, and handedness. The corpus callosum was segmented from T1 weighted images acquired with a Siemens 1.5 T scanner. Transformed coordinates of the curvilinear axis were aggregated into a parametric map and compared across series to derive regions of statistical significance. Our results indicate that a reduction in size of the corpus callosum occurs over all of its subdivisions (genu, body, splenium) in patients with autism. Since the commissural fibers that traverse the different anatomical compartments of the corpus callosum originate in disparate brain regions our results suggest the presence of widely distributed cortical abnormalities in people with autism.
- Published
- 2011
- Full Text
- View/download PDF
47. Antibodies to Costimulatory Receptor 4-1BB Enhance Anti-tumor Immunity via T Regulatory Cell Depletion and Promotion of CD8 T Cell Effector Function
- Author
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Björn Frendéus, Christine A. Penfold, Monika Semmrich, Emily L Williams, Steven G. Booth, Mats Jernetz, Anne Rogel, Ingrid Teige, Lekh N. Dahal, Jane E. Willoughby, Lang Dou, C. Ian Mockridge, J. Sjef Verbeek, Stuart N. Dunn, Kirstie L. S. Cleary, Juliet C. Gray, Chester Lai, Aymen Al-Shamkhani, Linda Mårtensson, Sarah L. Buchan, H.T. Claude Chan, Mark S. Cragg, Stephen A. Beers, Peter Johnson, Marcus Remer, Eugene Healy, Sonya James, Päivi Kannisto, and Martin J. Glennie
- Subjects
0301 basic medicine ,medicine.drug_class ,medicine.medical_treatment ,Immunology ,Gene Expression ,CD8-Positive T-Lymphocytes ,Monoclonal antibody ,T-Lymphocytes, Regulatory ,Immunomodulation ,Mice ,Tumor Necrosis Factor Receptor Superfamily, Member 9 ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,Immune system ,Antibody Isotype ,Neoplasms ,medicine ,Animals ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,Mice, Knockout ,biology ,Effector ,Antibodies, Monoclonal ,Immunotherapy ,Cell biology ,030104 developmental biology ,Infectious Diseases ,Immunoglobulin G ,030220 oncology & carcinogenesis ,biology.protein ,Antibody ,CD8 - Abstract
The costimulatory receptor 4-1BB is expressed on activated immune cells, including activated T cells. Antibodies targeting 4-1BB enhance the proliferation and survival of antigen-stimulated T cells in vitro and promote CD8 T cell-dependent anti-tumor immunity in pre-clinical cancer models. We found that T regulatory (Treg) cells infiltrating human or murine tumors expressed high amounts of 4-1BB. Intra-tumoral Treg cells were preferentially depleted by anti-4-1BB mAbs in vivo. Anti-4-1BB mAbs also promoted effector T cell agonism to promote tumor rejection. These distinct mechanisms were competitive and dependent on antibody isotype and FcγR availability. Administration of anti-4-1BB IgG2a, which preferentially depletes Treg cells, followed by either agonistic anti-4-1BB IgG1 or anti-PD-1 mAb augmented anti-tumor responses in multiple solid tumor models. An antibody engineered to optimize both FcγR-dependent Treg cell depleting capacity and FcγR-independent agonism delivered enhanced anti-tumor therapy. These insights into the effector mechanisms of anti-4-1BB mAbs lay the groundwork for translation into the clinic. Buchan et al. reveal dual anti-tumor activities for antibodies to the co-stimulatory receptor 4-1BB, which depend on antibody isotype and FcγR availability. Sequential scheduling of anti-4-1BB and checkpoint blockade mAbs, and antibodies engineered to harness both Treg cell depleting and effector cell agonism properties show potent anti-tumor activity in preclinical models, laying the groundwork for translation into the clinic.
- Published
- 2018
- Full Text
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48. Intervention Targeting Reductions In Sedentary Time In Older Cancer Survivors
- Author
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Amy Tarnower, Elizabeth M. Harding, Matthew R. Schwartz, Emily L. Williams, Cindy K. Blair, Charles L. Wiggins, David Medrano, and Anita Y. Kinney
- Subjects
Sedentary time ,Non responders ,medicine.medical_specialty ,business.industry ,Intervention (counseling) ,Internal medicine ,Medicine ,Cancer ,Physical Therapy, Sports Therapy and Rehabilitation ,Orthopedics and Sports Medicine ,business ,medicine.disease - Published
- 2018
- Full Text
- View/download PDF
49. Treatment of Vascular Malformations of the Female Genitalia: A Novel Approach
- Author
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Cate Barber, Emily L. Williams, Laura L. Hollenbach, and Gresham T. Richter
- Subjects
medicine.medical_specialty ,business.industry ,Pediatrics, Perinatology and Child Health ,Obstetrics and Gynecology ,Medicine ,General Medicine ,business ,Dermatology - Published
- 2018
- Full Text
- View/download PDF
50. PFAPA Syndrome: An atypical Cause of Genital Ulcers in the Adolescent Female
- Author
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Laura L. Hollenbach, Emily L. Williams, and Cate Barber
- Subjects
medicine.medical_specialty ,PFAPA syndrome ,business.industry ,Pediatrics, Perinatology and Child Health ,Obstetrics and Gynecology ,Medicine ,Sex organ ,General Medicine ,business ,Dermatology - Published
- 2018
- Full Text
- View/download PDF
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