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Appropriation of GPIb from platelet-derived extracellular vesicles supports monocyte recruitment in systemic inflammation
Get PDFInteractions between platelets, leukocytes and the vessel wall provide alternative pathological routes of thrombo-inflammatory leukocyte recruitment. We found that when platelets were activated by a range of agonists in whole blood, they shed platelet-derived extracellular vesicles which rapidly and preferentially bound to blood monocytes compared to other leukocytes. Platelet-derived extracellular vesicle binding to monocytes was initiated by P-selectin-dependent adhesion and was stabilised by binding of phosphatidylserine. These interactions resulted in the progressive transfer of the platelet adhesion receptor GPIbα to monocytes. GPIbα+-monocytes tethered and rolled on immobilised von Willebrand Factor or were recruited and activated on endothelial cells treated with TGF-β1 to induce the expression of von Willebrand Factor. In both models monocyte adhesion was ablated by a function-blocking antibody against GPIbα. Monocytes could also bind platelet-derived extracellular vesicle in mouse blood in vitro and in vivo. Intratracheal instillations of diesel nanoparticles, to model chronic pulmonary inflammation, induced accumulation of GPIbα on circulating monocytes. In intravital experiments, GPIbα+-monocytes adhered to the microcirculation of the TGF-β1-stimulated cremaster muscle, while in the ApoE−/− model of atherosclerosis, GPIbα+-monocytes adhered to the carotid arteries. In trauma patients, monocytes bore platelet markers within 1 hour of injury, the levels of which correlated with severity of trauma and resulted in monocyte clearance from the circulation. Thus, we have defined a novel thrombo-inflammatory pathway in which platelet-derived extracellular vesicles transfer a platelet adhesion receptor to monocytes, allowing their recruitment in large and small blood vessels, and which is likely to be pathogenic
The Adoption of e-Government Services in Nigeria using UTUAT Model
Get PDFElectronic government implementation in many
developing countries are still evolving and its realisation depends
on government provisions and users' adoption of the electronic
services. This work investigated Citizens’ adoption of egovernment services in Nigeria using the Unified Theory of
Acceptance and Use of Technology model (UTUAT). A survey
data was collected from 989 citizens of Nigeria from Public and
Private sectors.
The empirical finding shows that effort expectancy; performance
expectancy; and social influence determine citizens' behavioural
intention. Additionally, facilitating conditions, effort expectancy
and behavioural intentions determine citizens' use of egovernment services. Suggestions for decision makers and areas
for further research are also considered
Understanding well-being outcomes in primary care arts on referral interventions: a mixed method study
Get PDFBackground: Arts on Prescription programmes are designed to support mental health and well-being of patients with a variety of clinical needs within the community. Despite a number of studies reporting benefits, there are some patients that do not see improvements in well-being. Yet, there is limited research investigating the reasons for this. Methods: Using a sequential mixed-methods design the present study sought to understand why some participants (N=312) experienced an increase in well-being and others did not (N=95) after attending an Arts on Prescription intervention based in the South West of England between 2009 and 2016. Results: Quantitative comparisons between the two groups identified little differences, aside from age and baseline well-being (WEMWBS scores), with those that improved being slightly younger, and having lower well-being at the outset compared with those that did not improve. A process model depicting the perceived facilitative and inhibitive factors of attending the programme was developed from the qualitative findings. This model suggests that the social aspect of the course may be implicated in the participants differential outcomes; with those that showed a decrease in well-being reporting difficulties in interacting with others during the intervention. Further, the participants who reported an increase in well-being felt vulnerable to “relapse” when finishing the course due to uncertainties regarding future support and at their ability to maintain their well-being without the provision of the programme. Conclusions: This research suggests a need to promote communication amongst groups in such interventions with the hope that this will provide a more facilitative environment for all participants to benefit. Also, such programmes should consider follow-on options to ensure the participants feel supported and confident in managing their well-being once the course comes to an end. Findings will be pertinent to those commissioning primary care art interventions, ensuring that referral policies and pathways are designed for optimal effectiveness and for potentially tailoring social prescribing programmes to suit the participants specific needs
Development, Implementation, and Evaluation of an Athlete-Informed Mental Skills Training Program for Elite Youth Tennis Players
Get PDFInformed by athletes’ psychological needs, the current qualitative study developed, implemented, and evaluated a 15-month mental skills training (MST) program for elite youth athletes. The MST was divided into three phases that included a nine-month pre-intervention, a two-month intervention, and a four-month evaluation phase. The intervention consisted of three interactive workshops which were delivered to 11 competitive British youth tennis players (aged 8 to 15 years) and their coach (age =34). The intervention was informed by data that was collected throughout a nine-month pre-intervention phase including longitudinal observations, field notes, and semi-structured interviews. The intervention was evaluated over a four-month period through observations, field notes, athlete-workshop data, and a semi-structured interview with the coach. Results reinforced the value of the longitudinal pre-intervention phase by highlighting that the establishment of rapport between the researcher and athletes enhanced the meaningfulness and content of the MST program. Additionally, an increase in athletes’ use and regulation of PSCs was identified as a result of athletes’ improved understanding of psychological skills (i.e., self-talk, imagery, performance routines) and characteristics (i.e., focus, emotional control) (PSCs). Finally, the MST program fostered a shared subject specific language between athletes and their coach, enhancing the openness and frequency with which PSCs were talked about. Practical guidelines for future sport psychology interventions with youth athletes and their coaches are provided
Inflammatory adipocyte-derived extracellular vesicles promote leukocyte attachment to vascular endothelial cells
Get PDFBackground and aims.
Obesity is associated with an increased risk of cardiovascular disease, but the mechanisms involved are not completely understood. In obesity, the adipocyte microenvironment is characterised by both hypoxia and inflammation. Therefore, we sought to determine whether extracellular vesicles (EVs) derived from adipocytes in this setting might be involved in mediating cardiovascular disease, specifically by promoting leukocyte attachment to vascular endothelial cells.
Methods.
Mature 3T3-L1 adipocytes were incubated for 24 h under control, TNF-α (30 ng/mL), hypoxia (1% O2), or TNF-α+hypoxia (30 ng/mL, 1% O2) conditions. EVs were isolated by differential ultracentrifugation and analysed by nanoparticle tracking analysis. Primary human umbilical vein endothelial cells (HUVECs) were treated with EVs for 6 h before being lysed for Western blotting to investigate changes in adhesion molecule production, or for use in leukocyte attachment assays.
Results.
EVs from adipocytes treated with TNF-α and TNF-α+hypoxia increased vascular cell adhesion molecule (VCAM-1) production in HUVECs compared to basal level (4.2 ± 0.6 and 3.8 ± 0.3-fold increase, respectively (p < 0.05)), an effect that was inhibited by an anti-TNF-α neutralising antibody. Production of other adhesion molecules (E-selectin, P-selectin, platelet endothelial cell adhesion molecule and VE-Cadherin) was unchanged. Pre-incubating HUVECs with TNF-α+hypoxia EVs significantly increased leukocyte attachment compared to basal level (3.0 ± 0.4-fold increase (p < 0.05)).
Conclusions.
Inflammatory adipocyte EVs induce VCAM-1 production in vascular endothelial cells, accompanied by enhanced leukocyte attachment. Preventing adipocyte derived EV-induced VCAM-1 upregulation may offer a novel therapeutic target in the prevention of obesity-driven cardiovascular disease
Imagining a digital future: how could we design for enchantment within the special education curriculum?
Get PDFThe implementation of the new “Successful Futures” curriculum in the UK, means that
learners between the ages of 3 to 16 will be challenged to use digital media to develop their
life skills, personal confidence, work skills, career planning, health and well-being (Donaldson,
2015). Teaching staff, responsible for delivering this multi-faceted programme for learners
with profound disabilities, have reported that the perceived benefits of technology are
misaligned to individual needs and capabilities. This is particularly evident when combined
with a developmental approach that favours the achievement of milestones rather than
discovery-led, task free, interaction (Simmons, 2019). The work reported here aims to directly
address these gaps. We describe a series of Digital Imagining workshops, which set out to
encourage creative and co-productive relationships between teaching professionals,
academic artists, makers and computer scientists. During the activities, we experimented with
digital fabrication tools as a means to envision contingent, imaginative interactions between
learners with Profound and Multiple Learning Disabilities (PMLD), other people and their
environment. In collectively critiquing the ideas developed during the workshops participants
recognized the benefit of simple contingent, cause and effect actions for drawing attention to
the material properties of objects. Almost seamlessly, these sensory explorations became the
trigger for more complex ideas for integrating the demands of the digital curriculum into more
natural daily scenarios. The shared process of ideation and tinkering was reported to be vital
in generating a shift toward inclusion as a creative, imaginative and expressive counterpoint
to the pervasive emphasis on utility and function
How student engagement has been enhanced through research into factors affecting creativity
Get PDFStudent engagement is critical in helping students learn effectively and achieve success. For students working in the areas of art and design, there is also a strong emphasis placed on the importance of creativity. Over recent years we have conducted research into the factors and processes affecting creativity and explored how these insights can help improve student engagement and student creativity. The paper discusses the relationship between factors affecting student engagement and creativity; how our curriculum has been designed to develop student creativity; and how we have evaluated and refined our curriculum to enhance student engagement, based on our research into creativity. We present results from the National Student Survey (NSS) and from our own internal qualitative and quantitative data analysis highlighting areas where we have made a positive impact on student engagement. We also reflect on areas for further development and the possible impact our approach and curriculum design could have on other disciplines
How prisoners and their partners experience the maintenance of their relationship during a prison sentence
Get PDFResearch shows that intimate relationships, and their maintenance via prison visits, have a positive impact on factors associated with prisoner well‐being and reduced likelihood of recidivism. It is therefore in the interest of corrections, government, and wider society to enable prisoners to maintain healthy relationships with their family and intimate partners throughout their prison sentence. Despite this evidence, little is known about how prisoners experience the maintenance of a significant intimate relationship in prison. This study aims to explore heterosexual couples' experiences in maintaining their well‐established intimate relationships, while the male partner is incarcerated. Four main themes were identified: how they experienced “having a special connection” that they were motivated to maintain; “coping with challenges and threats” to that connection; “developing reciprocal behaviours” to meet those challenges; and “maintaining a belief in the future.” Implications for how the relational context of rehabilitation can best be supported is considered
Inner ear pressure evaluation using wideband tympanometry in children with Large Vestibular Aqueduct Syndrome (LVAS): A pilot study
Get PDFObjective
To investigate middle ear function in children with Large Vestibular Aqueduct Syndrome (LVAS) to explore the feasibility of measuring inner ear pressure using Wideband tympanometry (WBT).
Methods
13 young children with LVAS were recruited. WBT and other audiological measurements i.e., Auditory Steady State Response (ASSR), Auditory Brain Stem Response (ABR), and Distorted Product Otoacoustic Emissions (DPOAE) were performed. Absorbance under ambient and peak pressure were compared with normative data, and analyzed using a one sample t-test.
Results
Average absorbance in children with LVAS was significantly lower than normative data under ambient pressure at 1000, 1189, 1296, 2000 Hz and 4000 Hz. Absorbance under peak pressure was also significantly lower at 707, 794, 917, 1000, 1189, 1297, 1498 and 2000 Hz. However, absorbance was higher than standard values above 4000 Hz under ambient and peak pressure. It was also higher under ambient pressure at frequencies below 500 Hz.
Conclusion
The special characteristics of middle ear function found in children with Large Vestibular Aqueduct Syndrome (LVAS) indicate that WBT offers a sensitive and non-invasive method to evaluate inner ear pressure indirectly
Applying mastery TARGET structures to Cooperative Learning in PE
Get PDFThe purpose of this article is to critically apply the mastery TARGET structures (task, authority, recognition, grouping, evaluation and time) to the Cooperative Learning model in Physical Education. The premise is that the TARGET structures are highly applicable to the Cooperative Learning model and that combining both approaches will optimize student motivation in PE. The structure of the article follows the TARGET acronym and identifies how implementing each of the mastery TARGET structures could potentially enhance the motivational climate associated with the Cooperative Learning model. In doing so, the article, firstly introduces each of the TARGET structures and then critically applies them to the Cooperative Learning model in a PE context. The key elements of Cooperative Learning; positive interdependence, individual accountability, face-face interaction, interpersonal and small group skills, and group processing have close links with a number of the TARGET structures and these are critically explored. It is anticipated that this article could be used to further enrich the Cooperative Learning model and to open up new avenues of research that combine TARGET and Cooperative Learning