Results of the feasibility phase of the Managed Activity Graded Exercise iN Teenagers and PreAdolescents (MAGENTA) Randomised Controlled Trial of treatments for Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis

Background: Chronic fatigue syndrome (CFS) also known as myalgic encephalomyelitis (ME) is relatively common in young people and causes significant disability. Graded exercise therapy (GET) and activity management are recommended by the National Institute for Health and Care Excellence (NICE) despite a limited evidence-base for either treatment in paediatric CFS/ME. This paper reports on feasibility and acceptability measures from the feasibility phase of the ongoing MAGENTA randomised controlled trial (RCT) investigating GET versus activity management for young people with CFS/ME. Methods: Setting: Three specialist secondary care National Health Service (NHS) Paediatric CFS/ME services (Bath, Cambridge and Newcastle). Participants: Young people aged 8-17 years with a diagnosis of mild to moderate CFS/ME. Young people were excluded if they were severely affected, referred to cognitive behavioural therapy (CBT) at initial assessment or unable to attend clinical sessions. Interventions: GET and activity management delivered by physiotherapists, occupational therapists, nurses and psychologists. Families and clinicians decided the number (typically 8-12) and frequency of appointments (typically every 2-6 weeks). Outcome Measures: Recruitment and follow-up statistics. We used integrated qualitative methodology to explore the feasibility and acceptability of the trial processes and the interventions. Results: 80/161 (49.7%) of eligible young people were recruited at two sites between September 2015 and August 2016, indicating recruitment to the trial was feasible. Most recruitment (78/80; 97.5%) took place at one centre. Recruitment consultations, online consent and interventions were acceptable, with less than 10% in each arm discontinuing trial treatment. Response rate to the primary outcome (the SF36-PFS at 6 months) was 91.4%. Recruitment, treatment and data collection were not feasible at one centre. The site was withdrawn from the study. In response to data collected, we optimised trial processes including using Skype for recruitment discussions; adapting recruiter training to improve recruitment discussions; amending the accelerometer information leaflets; shortening the resource use questionnaires; and offering interventions via Skype. These amendments have been incorporated into the full trial protocol. Conclusions: Conducting an RCT investigating GET versus activity management is feasible and acceptable for young people with CFS/ME. Trial registration: ISRCTN23962803 https://doi.org/10.1186/ISRCTN23962803, date of registration: 03 September 2015</p

Results of the feasibility phase of the Managed Activity Graded Exercise iN Teenagers and PreAdolescents (MAGENTA) Randomised Controlled Trial of treatments for Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis

Background: Chronic fatigue syndrome (CFS) also known as myalgic encephalomyelitis (ME) is relatively common in young people and causes significant disability. Graded exercise therapy (GET) and activity management are recommended by the National Institute for Health and Care Excellence (NICE) despite a limited evidence-base for either treatment in paediatric CFS/ME. This paper reports on feasibility and acceptability measures from the feasibility phase of the ongoing MAGENTA randomised controlled trial (RCT) investigating GET versus activity management for young people with CFS/ME. Methods: Setting: Three specialist secondary care National Health Service (NHS) Paediatric CFS/ME services (Bath, Cambridge and Newcastle). Participants: Young people aged 8-17 years with a diagnosis of mild to moderate CFS/ME. Young people were excluded if they were severely affected, referred to cognitive behavioural therapy (CBT) at initial assessment or unable to attend clinical sessions. Interventions: GET and activity management delivered by physiotherapists, occupational therapists, nurses and psychologists. Families and clinicians decided the number (typically 8-12) and frequency of appointments (typically every 2-6 weeks). Outcome Measures: Recruitment and follow-up statistics. We used integrated qualitative methodology to explore the feasibility and acceptability of the trial processes and the interventions. Results: 80/161 (49.7%) of eligible young people were recruited at two sites between September 2015 and August 2016, indicating recruitment to the trial was feasible. Most recruitment (78/80; 97.5%) took place at one centre. Recruitment consultations, online consent and interventions were acceptable, with less than 10% in each arm discontinuing trial treatment. Response rate to the primary outcome (the SF36-PFS at 6 months) was 91.4%. Recruitment, treatment and data collection were not feasible at one centre. The site was withdrawn from the study. In response to data collected, we optimised trial processes including using Skype for recruitment discussions; adapting recruiter training to improve recruitment discussions; amending the accelerometer information leaflets; shortening the resource use questionnaires; and offering interventions via Skype. These amendments have been incorporated into the full trial protocol. Conclusions: Conducting an RCT investigating GET versus activity management is feasible and acceptable for young people with CFS/ME. Trial registration: ISRCTN23962803 https://doi.org/10.1186/ISRCTN23962803, date of registration: 03 September 2015</p

Affection not affliction: The role of emotions in information systems and organizational change

Most IS research in both the technical/rational and socio-technical traditions ignores or marginalizes the emotionally charged behaviours through which individuals engage in, and cope with the consequences of, IS practice and associated organizational change. Even within the small body of work that engages with emotions through particular conceptual efforts, affections are often conceived as a phenomenon to be eradicated – an affliction requiring a cure. In this paper, I argue that emotions are always implicated in our lived experiences, crucially influencing how we come to our beliefs about what is good or bad, right or wrong. I draw from the theoretical work of Michel Foucault to argue for elaborating current notions of IS innovation as a moral and political struggle in which individuals’ beliefs and feelings are constantly tested. Finally, I demonstrate these ideas by reference to a case study that had considerable emotional impact, and highlight the implications for future work

Fc engineered ACE2-Fc is a potent multifunctional agent targeting SARS-CoV2

Joining a function-enhanced Fc-portion of human IgG to the SARS-CoV-2 entry receptor ACE2 produces an antiviral decoy with strain transcending virus neutralizing activity. SARS-CoV-2 neutralization and Fc-effector functions of ACE2-Fc decoy proteins, formatted with or without the ACE2 collectrin domain, were optimized by Fc-modification. The different Fc-modifications resulted in distinct effects on neutralization and effector functions. H429Y, a point mutation outside the binding sites for FcγRs or complement caused non-covalent oligomerization of the ACE2-Fc decoy proteins, abrogated FcγR interaction and enhanced SARS-CoV-2 neutralization. Another Fc mutation, H429F did not improve virus neutralization but resulted in increased C5b-C9 fixation and transformed ACE2-Fc to a potent mediator of complement-dependent cytotoxicity (CDC) against SARS-CoV-2 spike (S) expressing cells. Furthermore, modification of the Fc-glycan enhanced cell activation via FcγRIIIa. These different immune profiles demonstrate the capacity of Fc-based agents to be engineered to optimize different mechanisms of protection for SARS-CoV-2 and potentially other viral pathogens

Characterization of the recombinant human prostanoid DP receptor and identification of L-644,698, a novel selective DP agonist

1. A human embryonic kidney cell line [HEK 293(EBNA)] stably expressing the human recombinant prostaglandin D(2) (PGD(2)) receptor (hDP) has been characterized with respect to radioligand binding and signal transduction properties by use of prostanoids and prostanoid analogues. Radioligand binding studies included saturation analyses, the effects of nucleotide analogues, the initial rate of ligand-receptor association and equilibrium competition assays. In addition, adenosine 3′:5′-cyclic monophosphate (cyclic AMP) generation in response to ligand challenge was also measured, as this is the predominant hDP signalling pathway. 2. L-644,698 ((4-(3-(3-(3-hydroxyoctyl)-4-oxo-2-thiazolidinyl) propyl) benzoic acid) (racemate)) was identified as a novel ligand having high affinity for hDP with an inhibitor constant (K(i)) of 0.9 nM. This K(i) value was comparable to the K(i) values obtained in this study for ligands that have previously shown high affinity for DP: PGD(2) (0.6 nM), ZK 110841 (0.3 nM), BW245C (0.4 nM), and BW A868C (2.3 nM). 3. L-644,698 was found to be a full agonist with an EC(50) value of 0.5 nM in generating cyclic AMP following activation of hDP. L-644,698 is, therefore, comparable to those agonists with known efficacy at the DP receptor (EC(50)): PGD(2) (0.5 nM), ZK 110841 (0.2 nM) and BW245C (0.3 nM). 4. L-644,698 displayed a high degree of selectivity for hDP when compared to the family of cloned human prostanoid receptors: EP(1) (>25,400 fold), EP(2) (∼300 fold), EP(3-III) (∼4100 fold), EP(4) (∼10000 fold), FP (>25,400 fold), IP (>25,400 fold) and TP (>25,400 fold). L-644,698 is, therefore, one of the most selective DP agonists as yet described. 5. PGJ(2) and Δ(12)-PGJ(2), two endogenous metabolites of PGD(2), were also tested in this system and shown to be effective agonists with K(i) and EC(50) values in the nanomolar range for both compounds. In particular, PGJ(2) was equipotent to known DP specific agonists with a K(i) value of 0.9 nM and an EC(50) value of 1.2 nM

Theorizing about socio-technical approaches to HCI

In this paper, we theorize about Socio-Technical approaches to HCI. The Socio-Technical tradition indicates that looking at design only or mainly from a technical design side is insufficient to design systems for work and workers; instead the social and the technical need to be co-designed and contingent on characteristics of the context, the organisation, and its histor-ical development. However, it also argued that this tradition does not pro-vide enough handles for the design of interactive technologies for users. We present Socio-Technical HCI as a distinct field of knowledge outlining the Socio-Technical traditions where it is rooted, and illustrate these with three different conceptual frameworks that have been used to support the design, development, and evaluation of interactive systems. These frameworks are Cognitive Work Analysis, Human-Work Interaction Design, and Techno-logical Frames. These frameworks are compared and analysed in terms of what are a balanced and comprehensive way to in address socio-technical, contextual, and design issues in HCI. It is argued why Human-Work Inter-action Design is best placed to address these issues