A randomized, open-label comparison of once-weekly insulin icodec titration strategies versus once-daily insulin glargine u100

OBJECTIVE Insulin icodec is a novel once-weekly basal insulin analog. This trial investigated the efficacy and safety of icodec using different once-weekly titration algorithms. RESEARCH DESIGN AND METHODS This was a phase 2, randomized, open-label, 16-week, treat-to-target study. Insulin-naive adults (n = 205) with type 2 diabetes and HbA1c 7–10% while treated with oral glucose-lowering medications initiated once-weekly icodec titrations A (prebreakfast self-measured blood glucose target 80–130 mg/dL; adjustment ±21 units/week; n = 51), B (80–130 mg/dL; ±28 units/week; n = 51), or C (70–108 mg/dL; ±28 units/week; n = 52), or once-daily insulin glargine 100 units/mL (IGlar U100) (80–130 mg/dL; ±4 units/day; n = 51), all titrated weekly. Percentage of time in range (TIR) (70–180 mg/dL) during weeks 15 and 16 was measured using continuous glucose monitoring. RESULTS TIR improved from baseline (means: A, 57.0%;B,55.2%;C,51.0%; IGlar U100, 55.3%) to weeks 15 and 16 (estimated mean: A, 76.6%; B,83.0%; C,80.9%; IGlar U100, 75.9%). TIR was greater for titration B than for IGlar U100 (estimated treatment difference 7.08%-points; 95% CI 2.12 to 12.04; P = 0.005). No unexpected safety signals were observed. Level 2 hypoglycemia (<54 mg/dL) was low in all groups (0.05, 0.15, 0.38, 0.00 events per patient-year of exposure for icodec titrations A, B, and C and IGlar U100, respectively), with no episodes of severe hypoglycemia. CONCLUSIONS Once-weekly icodec was efficacious and well tolerated across all three titration algorithms investigated. The results for icodec titration A (80–130 mg/dL; ±21 units/week) displayed the best balance between glycemic control and risk of hypoglycemia

Mobile encounters:bus 5A as a cross-cultural meeting place

The paper explores modes of encounters in the everyday practice of bus travel. Particularly, it addresses cross-cultural encounters located in the tension between familiarity and difference, between inclusion and exclusion. The paper is located in contemporary thoughts, approaching public transport not only as a moving device but also as a social arena. Furthermore, the bus is simultaneously perceived as a public space, at once composite, contradictory and heterogeneous, and as a meeting place involving ‘Throwntogetherness’. The encounters analysed are bodily, emotional charged and outspoken meetings between passengers, with the socio-materiality of the bus and drivers as co-riders and gatekeepers

The state of the art: immune-mediated mechanisms of monoclonal antibodies in cancer therapy

A number of antibody products have now become accepted as effective anti-cancer therapies. Despite being mainly designed to act by inhibiting functional tumour antigens, there is increasing evidence that Fc-mediated engagement of the immune system is an important contributor to the efficacy of several of these therapies. The optimisation of this engagement offers the potential not only to augment efficacy against existing targets, but also to exploit non-functional tumour antigens. Antibodies that achieve efficacy wholly or predominantly through Fc-mediated mechanisms, represent rich opportunities for future therapeutics in oncology. This mini review summarises some of the key challenges, which need to be addressed to select the most effective molecules. These include the identification of optimal antibody characteristics and improvement of the drug discovery process, in particular, the relevance and predictive power of existing in vitro and in vivo screening methods. Advances in our understanding of tumour immunobiology and successful application of technologies designed to enhance immune system engagement will further aid this process

From Big Society to Shared Society? Geographies of social cohesion and encounter in the UK’s National Citizen Service

This article explores and expands debates on the geographies of social cohesion and encounter, specifically in relation to young people and informal citizenship training. Three questions drive our agenda in this paper. First, how do certain youth spaces get enrolled into wider political discourses, functioning as geographical expressions of government visions to create a political legacy? Second, how are these spaces engineered and operate on-the-ground? Finally, how do young people understand their experiences of such spaces? To address these questions, we use the example of ‘National Citizen Service’ – a youth programme operating in England and Northern Ireland – to raise critical questions about the wider politics of spaces of informal education and attempts by the state to ‘make’ citizens and future neighbours. The article examines the rationale for this growing scheme, targeted at 15–17 year olds and designed to foster a ‘more cohesive, responsible and engaged society’. Drawing on original fieldwork with key architects, stakeholders and young people, we analyse the narratives that underlie NCS and its expansion – specifically around social cohesion and citizenship education. We explore the idea of ‘social mix’ as one of NCS’ guiding principles and its place as part of state narratives about the ‘Big Society’ and ‘Shared Society’