Ultra-Long Pharmacokinetic Properties of Insulin Degludec are Comparable in Elderly Subjects and Younger Adults with Type 1 Diabetes Mellitus

BACKGROUND: Management of diabetes in elderly subjects is complex and careful management of glucose levels is of particular importance in this population because of an increased risk of diabetes-related complications and hypoglycaemia. OBJECTIVE: The aim of this study was to evaluate the pharmacokinetic and pharmacodynamic properties of insulin degludec (IDeg), a basal insulin with an ultra-long duration of action, in elderly subjects with type 1 diabetes compared with younger adults. METHODS: This trial was a randomised, double-blind, two-period, crossover trial conducted in a single centre and included both inpatient and outpatient periods. Subjects were men and women aged 18–35 years inclusive (younger adult group) or ≥65 years (elderly group) with type 1 diabetes who received IDeg (0.4 U/kg) via subcutaneous injection in the thigh once-daily for six days. Following 6-day dosing, a 26-hour euglycaemic glucose clamp procedure was conducted to evaluate the steady-state pharmacodynamic effects of IDeg. Blood samples were taken for pharmacokinetic analysis up to 120 h post-dose. Pharmacokinetic endpoints included the total exposure of IDeg, ie the area under the IDeg serum concentration curve during one dosing interval at steady state (AUC(IDeg,τ,SS)) (τ = 0–24 h, equal to one dosing interval) and the maximum IDeg serum concentration at steady state (C(max,IDeg,SS)). Pharmacodynamic endpoints included the total glucose-lowering effect of IDeg, ie the area under the glucose infusion rate (GIR) curve at steady state (AUC(GIR,τ,SS)), and the maximum GIR at steady state (GIR(max,IDeg,SS)). RESULTS: Total exposure (AUC(IDeg,τ,SS)) and maximum concentration (C(max,IDeg,SS)) of IDeg were comparable between elderly subjects and younger adults. Estimated mean age group ratios (elderly/younger adult) for AUC(IDeg,τ,SS) and C(max,IDeg,SS) and corresponding two-sided 95 % confidence intervals (CIs) were 1.04 (95 % CI 0.73–1.47) and 1.02 (95 % CI 0.74–1.39), respectively. Mean AUC(IDeg,0–12h,SS)/AUC(IDeg,τ,SS) was 53 % in both younger adult and elderly subjects, showing that in both age groups IDeg exposure was evenly distributed across the first and second 12 h of the 24-hour dosing interval. No statistically significant differences were observed between younger adult and elderly subjects with regard to AUC(GIR,τ,SS) (the primary endpoint of this study) and GIR(max,IDeg,SS). Estimated mean age group ratios (elderly/younger adult) for AUC(GIR,τ,SS) and GIR(max,IDeg,SS) and corresponding two-sided 95 % CIs were 0.78 (95 % CI 0.47–1.31) and 0.80 (95 % CI 0.54–1.17), respectively. Duration of action was beyond the clamp duration of 26 h in all subjects. CONCLUSIONS: The exposure of IDeg at steady state during once-daily dosing was similar in younger adult and elderly subjects. The glucose-lowering effect of IDeg was numerically lower in elderly subjects compared with younger adults, but no significant differences were observed between age groups. The ultra-long pharmacokinetic and pharmacodynamic properties of IDeg observed in younger adults were preserved in elderly subjects with type 1 diabetes. Clinical trials.gov number: NCT0096441

When does the action start and finish? Making the case for an ethnographic action research in educational research

This paper explores how ethnographic and action research methodologies can be justifiably combined to create a new methodological approach in educational research. It draws on existing examples in both educational research and development studies that have discussed the use of ethnography and action research in specific projects. Interpretations of ethnography and action research are developed that aim to minimise the epistemological differences between them. The paper also contextualises an ‘ethnographic action research’ approach with reference to an example of the author’s research into participation in three ‘reception’ (first year of schooling) classes in the United Kingdom. It is argued that research into the theme of participation in early years education, using participative methods, was particularly suitable for this new methodological approach

Communicating climate knowledge proxies, processes, politics

This forum article is the product of interdisciplinary discussion at a conference on climate histories held inCambridge, United Kingdom, in early 2011, with the specific aim of building a network around the issue of communicating cultural knowledge of environmental change. The lead articles, by Kirsten Hastrup as an anthropologist and Simon Schaffer as a historian of science, highlight the role of agents and proxies. These are followed by five interdisciplinary commentaries, which engage with the lead articles through new ethnographic material, and a set of shorter commentaries by leading scholars of different disciplines. Finally, the lead authors respond to the discussion. In this debate, climate change does not emerge as a single preformed "problem." Rather, different climate knowledges appear as products of particular networks and agencies. Just as the identification of proxies creates agents (ice, mountains, informants) by inserting them into new networks, we hope that these cross-disciplinary exchanges will produce further conversations and new approaches to action. © 2012 by The Wenner-Gren Foundation for Anthropological Research

Напряженное состояние призабойной части массива при проведении горных выработок с конической формой забоя

У рамках механіки пружно-деформованого тіла розроблена методика та розв’язана задача про напружений стан гірського масиву навколо горизонтальної циліндричної виробки. Чисельними дослідженнями виявлено значну концентрацію розтягуючих напружень у зоні ведення гірничих робіт.A method of stress state of a rock massif near the horizontal cylindrical working is developed, and a problem of mechanics of elastically deformed bodies is solved. A considerable concentration of tensile stresses in the mining working zone is revealed by numerical calculations

Risk of heart failure among individuals tested for Borrelia burgdorferi sensu lato antibodies, and serum Borrelia burgdorferi sensu lato seropositive individuals; a nationwide population-based, registry-based matched cohort study

BACKGROUND: Lyme borreliosis is a tick-borne disease caused by the bacterium Borrelia burgdorferi (Bb) sensu lato complex. Previous studies have suggested an association between Lyme borreliosis and heart failure, which have been suggested to be a possible manifestation of Lyme carditis. We aimed to investigate the risk of heart failure among individuals tested for serum Bb antibodies, and serum Bb seropositive individuals.METHODS: We performed a matched nationwide cohort study (Denmark, 1993-2020) and included 52,200 Bb seropositive individuals, and two age- and sex-matched comparison cohorts: 1) 104,400 Bb seronegative comparison cohort members, and 2) 261,000 population controls. We investigated the risk associated with 1) being tested for serum Bb antibodies, and 2) being Bb seropositive. Outcomes were: 1) a composite of heart failure, cardiomyopathy, and/or myocarditis diagnosis, and 2) redemption of cardiovascular medicine used for treatment of heart failure. We calculated short-term odds ratios (aOR) (within 1 month) and long-term hazard rates (aHR) (after 1 month) adjusted for age, sex, diabetes, pre-existing heart failure, and kidney disease.RESULTS: Compared with the population controls, individuals tested for Bb antibodies, regardless of the test result, had increased short-term risk of heart failure, cardiomyopathy, and myocarditis (aOR 8.3, 95 %CI: 6.7-10.2), and both increased short- and long-term risk of redemption of cardiovascular medicine (aOR 4.3, 95 %CI: 3.8-4.8, aHR 1.13, 95 % CI: 1.11-1.15). The Bb seropositive individuals had no increased short- or long-term risk of any outcome compared with Bb seronegative comparison cohort members.CONCLUSIONS: In conclusion, Bb antibody tests seemed to be performed in the diagnostic work-up of heart failure, but Bb seropositivity was not associated with heart failure.</p

Framing rights and responsibilities: accounts of women with a history of AIDS activism

<p>Abstract</p> <p>Background</p> <p>In South Africa, policy with respect to HIV/AIDS has had a strong rights-based framing in line with international trends and in keeping with the constitutional overhaul in the post-Apartheid era. There have also been considerable advances since 1994 towards legal enshrinement of sexual and reproductive health rights and in the provision of related services. Since HIV in this setting has heavily affected women of reproductive age, there has been discussion about the particular needs of this subgroup, especially in the context of service integration. This paper is concerned with the way in which HIV positive women conceptualise these rights and whether they wish and are able to actualise them in their daily lives.</p> <p>Methods</p> <p>In 2003 a group of women involved with the Treatment Action Campaign and Medicines Sans Frontières participated in an initiative to ‘map’ their bodies as affected by the virus. A book containing the maps and narratives was published and used as a political tool to pressure the government of the day to roll out antiretroviral therapy (ART) to the population. In 2008, the authors coordinated an initiative that involved conducting follow-up in-depth interviews in which five of these women reflected on those body maps and on how their lives had changed in the intervening five years since gaining the right to treatment through the public sector.</p> <p>Results</p> <p>Drawing upon this qualitative data and published sources, these new accounts are analysed in order to reflect the perspectives of these women living with chronic HIV with respect to their sexual relations and fertility desires. The paper reveals difficulties faced by these women in negotiating sexual relationships and disclosure of their HIV positive status. It focuses on how they perceive relative responsibilities in terms of taking preventative measures in sexual encounters. Women adopt tactics within a context characterised by various inequalities in order to ‘make do’, such as by remaining silent about their status. Concerns about childbearing can be addressed by information and support from a health care worker.</p> <p>Conclusions</p> <p>Women’s experience of HIV as a chronic illness and the need to adhere to ART, is linked to the way in which the language of responsibility can come to counter-balance a language of rights in treatment programmes.</p