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Background Digital contact tracing is employed to monitor and manage the spread of COVID-19. However, to be effective the system must be adopted by a substantial proportion of the population. Studies of mostly hypothetical contact tracing apps show generally high acceptance, but little is known about the drivers and barriers to adoption of deployed systems. Objective The aim of this study was to investigate adoption of and attitudes toward the NHS (National Health Service) COVID-19 smartphone app, the digital contact tracing solution in the United Kingdom. Methods An online survey based on the extended Technology Acceptance Model with the added factor of trust was carried out with a representative sample of the UK population. Statistical analysis showed adoption rates, attitudes toward and trust in the app, and compliance with self-isolation advice and highlighted differences for vulnerable populations (ie, older adults aged 65 years and over and members of Black, Asian, and minority ethnic [BAME] communities). Results A total of 1001 participants took part in the study. Around half of the participants who had heard of the NHS COVID-19 mobile phone app (490/963, 50.9%; 95% CI 47.8%-54.0%) had downloaded and kept the app, but more than one-third (345/963, 35.8%; 95% CI 32.8%-38.8%) either did not intend to download it or had deleted it. Significantly more BAME respondents than White respondents had deleted the app (16/115, 13.9%; 95% CI 11.8%-16.0%, vs 65/876, 7.4%; 95% CI 5.8%-9.0%), and significantly more older adults 65 years and over than those under 65 years did not intend to download it (44/127, 34.6%; 95% CI 31.7%-37.5%, vs 220/874, 25.2%; 95% CI 22.5%-27.9%). Broadly, one of the reasons for uptake was to help the NHS and other people, especially among older adults, although significantly fewer BAME participants agreed that they did so to help the NHS. Reported compliance with received notifications to self-isolate was high but was significantly lower than reported intended compliance without received notifications. Only one-fifth (136/699, 19.5%; 95% CI 17.0%-22.0%) of participants understood that the decision to send self-isolation notifications was automated by the app. There were a range of significantly more negative views among BAME participants, including lower trust in the NHS, while older adults were often significantly more positive. Respondents without the app reported significantly lower trust and more negative views toward the app and were less likely to report that they understood how the app works. Conclusions While compliance on the part of the approximately 50% of participants who had the app was fairly high, there were issues surrounding trust and understanding that hindered adoption and, therefore, the effectiveness of digital contact tracing, particularly among BAME communities. This study highlights that more needs to be done to improve adoption among groups who are more vulnerable to the effects of the virus in order to enhance uptake and acceptance of contact tracing apps.

During the COVID-19 pandemic, digital contact-tracing has been employed in many countries to monitor and manage the spread of the disease. However, to be effective such a system must be adopted by a substantial proportion of the population; therefore, public trust plays a key role. This paper examines the NHS COVID-19 smartphone app, the digital contact-tracing solution in the UK. A series of interviews were carried out prior to the app’s release (n = 12) and a large scale survey examining attitudes towards the app (n = 1,001) was carried out after release. Extending previous work reporting high level attitudes towards the app, this paper shows that prevailing negative attitudes prior to release persisted, and affected the subsequent use of the app. They also show significant relationships between trust, app features, and the wider social and societal context. There is lower trust amongst non-users of the app and trust correlates to many other aspects of the app, a lack of trust could hinder adoption and effectiveness of digital contact-tracing. The design of technology requiring wide uptake, e.g., for public health, should embed considerations of the complexities of trust and the context in which the technology will be used.

This study aims to capture the online experiences of young people when interacting with algorithm mediated systems and their impact on their well-being. We draw on qualitative (focus groups) and quantitative (survey) data from a total of 260 young people to bring their opinions to the forefront while eliciting discussions. The results of the study revealed the young people’s positive as well as negative experiences of using online platforms. Benefits such as convenience, entertainment and personalised search results were identified. However, the data also reveals participants’ concerns for their privacy, safety and trust when online, which can have a significant impact on their well-being. We conclude by recommending that online platforms acknowledge and enact on their responsibility to protect the privacy of their young users, recognising the significant developmental milestones that this group experience during these early years, and the impact that algorithm mediated systems may have on them. We argue that governments need to incorporate policies that require technologists and others to embed the safeguarding of users’ well-being within the core of the design of Internet products and services to improve the user experiences and psychological well-being of all, but especially those of children and young people.

The 5Rights Youth Juries are an educational intervention to promote digital literacy by engaging participants (i.e. jurors) in a deliberative discussion around their digital rights. The main objective of these jury-styled focus groups is to encourage children and young people to identify online concerns and solutions with a view to developing recommendations for government policy-makers and industry chiefs. The methodology included a series of dramatized scenarios that encourage jurors to deliberate about their digital rights. This paper compares two formats for these scenarios: live actors and professionally recorded and edited videos of the same actors. Results failed to show any major differences between formats indicating the cost-effectiveness of the video-recorded format and the possibility for others to run the 5Rights Youth Juries with the support of an online open educational resource.

OBJECTIVE: Notch signalling has been implicated in haematopoietic stem cell self-renewal. Although several studies have tested the effect of activating or inhibiting the Notch signalling pathway in stem cells, no study has yet determined the functional differences associated with expressing Notch1. The aims of this study were to characterise the expression of human cell-surface Notch1 in cord blood (CB) CD34(+) cells and to study the function of Notch in CD34(+) cells in vitro. METHODS: A monoclonal antibody against the extracellular domain of Notch1 was developed, and Notch1 expression in CB CD34(+) cells was assessed by flow cytometry. CB CD34(+) cells were sorted on the basis of their Notch1 expression and cultured in serum-free media. Single sorted CD34(+) CD38(-) Notch1(+) /(-) cells were cultured for 8 wks on murine stroma monolayers and assayed for stem cell activity and lineage potential using a cobblestone area-forming cell (CAFC) assay. RESULTS: Cell-surface Notch1 expression was characterised in various primitive CD34(+) cell compartments including a small subpopulation of CD34(+) CD38(-) cells. We found the CD34(+) CD38(-) Notch1(+) population to be enriched for stem cell activity. Moreover, CD34(+) CD38(-) Notch1(+) , but not Notch1(-) cells, demonstrated multilineage potential. CONCLUSIONS: These data show that Notch1 is expressed on a functionally distinct subpopulation of CD34(+) cells that is highly enriched for stem cell activity and multilineage potential and could suggest that Notch1 could be used as a novel stem cell marker.

Recent studies have highlighted the role of Notch signalling in the development of T cell acute lymphoblasic leukaemia (T-ALL). Over-expression of Notch3 and gain of function mutations in the Notch1 gene have been reported. The aims of this study were to determine the effect of Notch signalling on apoptosis in human T-ALL cell lines and to identify targets of Notch signalling that may mediate this effect. Functional studies showed that inhibition of Notch signalling using gamma secretase inhibitors promoted glucocorticoid-induced apoptosis in cells carrying gain of function mutations in Notch1. Moreover, ectopic expression of constitutively activated Notch provided protection against glucocorticoid-induced apoptosis, indicating that signalling via Notch may also contribute to the development of T-ALL by conferring resistance to apoptosis. Microarray analysis revealed that GIMAP5, a gene coding for an anti-apoptotic intracellular protein, is upregulated by Notch in T-ALL cell lines. Knockdown of GIMAP5 expression using siRNA promoted glucocorticoid-induced apoptosis in T-ALL cells carrying gain of function mutations in Notch1 and in T-ALL cells engineered to express ectopic constitutively activated Notch indicating that Notch signalling protects T-ALL cells from apoptosis by upregulating the expression of GIMAP5.

Most of the recent evidence suggests that the avermectin/milbemycin family of anthelmintics act via specific interactions with glutamate-gated chloride channels. These channels are encoded by a small family of genes in nematodes, though the composition of the gene family and the function of the individual members of the family may vary between species. We review our current knowledge concerning the properties of the glutamate-gated chloride channels from Caenorhabditis elegans and the related parasite, Haemonchus contortus. We conclude that the biological effects of the avermectins/milbemycins can be largely explained by the known pharmacology and distribution of the glutamate-gated chloride channels and that differences between the glutamate-gated chloride channels from different nematodes may underlie species-specific variations in anthelmintic action.

Background Dysregulated Notch signalling is believed to play an important role in the development and maintenance of T cell leukaemia. At a cellular level, Notch signalling promotes proliferation and inhibits apoptosis of T cell acute lymphoblastic leukaemia (T-ALL) cells. In this study we aimed to identify novel transcriptional targets of Notch signalling in the T-ALL cell line, Jurkat. Results RNA was prepared from Jurkat cells retrovirally transduced with an empty vector (GFP-alone) or vectors containing constitutively active forms of Notch (N1ΔE or N3ΔE), and used for Affymetrix microarray analysis. A subset of genes found to be regulated by Notch was chosen for real-time PCR validation and in some cases, validation at the protein level, using several Notch-transduced T-ALL and non-T-ALL leukaemic cell lines. As expected, several known transcriptional target of Notch, such as HES1 and Deltex, were found to be overexpressed in Notch-transduced cells, however, many novel transcriptional targets of Notch signalling were identified using this approach. These included the T cell costimulatory molecule CD28, the anti-apoptotic protein GIMAP5, and inhibitor of DNA binding 1 (1D1). Conclusion The identification of such downstream Notch target genes provides insights into the mechanisms of Notch function in T cell leukaemia, and may help identify novel therapeutic targets in this disease.