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This paper presents a new methodological approach, TrustScapes, an open access tool designed to identify and visualise stakeholders' concerns and policy recommendations on data protection, algorithmic bias, and online safety for a fairer and more trustworthy online world. We first describe how the tool was co-created with young people and other stakeholders through a series of workshops. We then present two sets of TrustScapes focus groups to illustrate how the tool can be used, and the data analysed. The paper then provides the methodological insights, including the strengths of the TrustScapes and the lessons for future research using TrustScapes. A key strength of this method is that it allows people to visualise their ideas and thoughts on the worksheet, using the keywords and sketches provided. The flexibility in the mode of delivery is another strength of the TrustScapes method. The TrustScapes focus groups can be conducted in a relatively short time (1.5–2 hours), either in person or online depending on the participants' needs, geological locations, and practicality. Our experience with the TrustScapes offers some lessons (related to the data collection and analysis) for researchers who wish to use this method in the future. Finally, we describe how the outcomes from the TrustScapes focus groups should help to inform future policy decisions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (GFPalone) or vectors containing constitutively active forms of Notch (N1?E or N3?E), 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 Notchtransduced 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. [ABSTRACT FROM AUTHOR]

This work describes a new gene coding for a fatty acid binding protein (FABP) in the parasite Echinococcus granulosus, named EgFABP2. The complete gene structure, including the promoter sequence, is reported. The genomic coding domain organisation of the previously reported E. granulosus FABP gene (EgFABP1) has been also determined. The corresponding polypeptide chains share 76% of identical residues and an overall 96% of similarity. The two EgFABPs present the highest amino acid homologies with the mammalian FABP subfamily containing heart-FABPs (H-FABPs). The coding sequences of both genes are interrupted by a single intron located in the position of the third intron reported for vertebrate FABP genes. Both genes are expressed in the protoscolex stage of the parasite. The promoter region of EgFABP2 presents several consensus putative cis-acting elements found in other members of the family, suggesting interesting possible mechanisms involved in the host–parasite adaptation. [Copyright &y& Elsevier]

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 is to investigate adoption and attitudes towards the NHS Covid-19 smartphone app, the digital contact tracing solution in the UK.Methods: An online survey based on the technology acceptance model (TAM2) with the added factor of trust was carried out with a representative sample of the UK population. Statistical analysis shows adoption rates, attitudes towards and trust in the app, compliance with self-isolation advice, and highlights differences for vulnerable populations (older adults over 65 years of age and members of Black, Asian, and Minority Ethnic (BAME) communities).Results: Around half of the 1,001 (50.9%, 95% CI:47.8-54.0%) respondents had downloaded and kept the app, but more than a third (35.8%, CI:32.8-38.8%) either did not intend to download it or had deleted it. Significantly more BAME respondents had deleted the app (13.9%, CI :11.8-16.0%, vs 7.4%, CI: 5.8-9.0%), and significantly more older adults over 65 years old did not intend to download it (34.6%, CI: 31.7-37.5% vs 25.2% CI: 22.5-27.9%). Reasons for uptake were broadly to help the NHS and other people, especially among older adults, although significantly fewer BAME agreed that they did so to help the NHS. Reported compliance with received notifications to self-isolate was high, but significantly lower than reported intended compliance without received notifications. Only a fifth (19.5%, CI: 17.0-22.0%) understood that the decision to send self-isolation notifications is automated by the app. There were a range of significantly more negative views among BAME participants, including lower trust in the NHS, whilst older adults were often significantly more positive. Respondents without the app reported significantly lower trust and more negative views towards the app and were less likely to report they understood how the app works.Conclusions: Whilst compliance of the ~50% who have the app is fairly high, there are issues surrounding trust and understanding that hinder adoption and therefore the effectiveness of digital contact tracing, particularly amongst BAME communities. The study highlights that more needs to be done to improve adoption among groups who are more vulnerable to the effects of the virus to enhance uptake and acceptance of contact tracing apps.Clinicaltrial: [ABSTRACT FROM AUTHOR]

Abstract: The target site for the anthelmintic action of ivermectin is a family of nematode glutamate-gated chloride channel alpha subunits (GluClα) that bind the drug with high affinity and mediate its potent paralytic action. Whilst the action of ivermectin on the pharyngeal muscle of nematodes is relatively well understood, its effect on locomotor activity is less clear. Here we use RNAi and gene knockouts to show that four GluClα subunits are involved in regulating the pattern of locomotor activity in Caenorhabditis elegans. A Haemonchus contortus orthologue of these subunits, HcGluClα3, has been shown to be expressed in the motor nervous system and here we have shown that it is a functional, as well as a structural, orthologue by virtue of the observation that it can restore normal motor movement in the C. elegans GluClα mutant, avr-14(ad1032), when expressed under the control of the avr-14 promoter. This supports the contention that ivermectin exerts its paralytic action on parasitic nematodes through activation of GluCl channels in the motor nervous system. Furthermore, functional complementation in C. elegans provides a method to further the understanding of this important class of anthelmintic targets. [Copyright &y& Elsevier]

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., (©Liz Dowthwaite, Joel Fischer, Elvira Perez Vallejos, Virginia Portillo, Elena Nichele, Murray Goulden, Derek McAuley. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 17.09.2021.)

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.

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., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Glutamate-gated chloride channels (GluCl) are related to gamma-aminobutyric acid-A (GABA(A)) receptors and are the target sites for the avermectin/milbemycin (A/M) anthelmintics, drugs that cause paralysis of the somatic and pharyngeal muscles in nematodes. We have previously identified four GluCl subunits, HcGluClalpha, HcGluClbeta, HcGluClalpha3A, and HcGluClalpha3B from the sheep parasite Haemonchus contortus. We raised specific antisera against all of these subunits and used them in immunofluorescence experiments on adult parasites. All of the subunits were expressed in the motor nervous system, especially motor neuron commissures. Double-immunostaining experiments suggested that HcGluClalpha and HcGluClbeta were expressed on the same commissures; these were also stained with an anti-GABA antibody, suggesting that they may be inhibitory motor neurons. The HcGluClbeta subunit was also detected in lateral and sublateral nerve cords. The HcGluClalpha3A and -B subunits, products of an alternatively spliced gene, were expressed in different neurons. We found HcGluClalphaA in a pair of sensory, possibly amphid, neurons in the head, in addition to the motor neuron commissures. HcGluClalpha3B was detected in three cell bodies, probably of pharyngeal neurons, and to ventral and lateral cords. These results indicate that the GluCl are widely distributed in the H. contortus nervous system and suggest that they have critical roles controlling locomotion, pharyngeal function, and possibly sensory processing in parasitic nematodes. They also provide an explanation for the observed effects of the A/M anthelmintics., (Copyright 2003 Wiley-Liss, Inc.)