Les régions françaises face aux perspectives de la mécanique moyenne française et à la politique de localisation de ses entreprises. L'exemple du Sillon alpin

Courlet C, Tiberghien R. Les régions françaises face aux perspectives de la mécanique moyenne française et à la politique de localisation de ses entreprises. L'exemple du Sillon alpin. In: Revue de géographie alpine, tome 63, n°4, 1975. pp. 533-541

Physiologically‐Based Pharmacokinetic Modeling Combined with Swiss HIV Cohort Study Data Supports No Dose Adjustment of Bictegravir in Elderly Individuals Living With HIV

Clinical studies in aging people living with HIV (PLWH) are sparse for the novel integrase inhibitor bictegravir, leading to some uncertainty about dosing recommendations for elderly PLWH. The objective of this study was to investigate the continuous impact of aging on bictegravir pharmacokinetics by combining clinically observed data with modeling to support a safe and efficient anti-HIV therapy with advanced age. A physiologically-based pharmacokinetic (PBPK) model was developed for bictegravir with clinically observed data from phase I studies. The predictive model performance was verified using bictegravir plasma concentrations sampled as part of the general therapeutic drug monitoring (TDM) program of the Swiss HIV Cohort Study in young (20-55 years) and elderly PLWH (55-85 years). The verified PBPK model subsequently predicted the continuous impact of aging on bictegravir pharmacokinetics across adulthood (20-99 years). Bictegravir exposure was unchanged in elderly compared with young PLWH when analyzing the TDM data of the Swiss HIV Cohort Study. PBPK simulations predicted clinically observed data from 60 young and 32 elderly PLWH mostly within the 95% confidence interval, demonstrating the predictive power of the used modeling approach. Simulations predicted drug exposure to increase up to 40% during adulthood, which was not statistically significantly different from the age-related pharmacokinetic changes of other HIV and non-HIV drugs. Sex had no impact on the age-related changes of bictegravir pharmacokinetics. Considering the safety margin of bictegravir, a dose adjustment for the novel integrase inhibitor is a priori not necessary in elderly PLWH in the absence of severe comorbidities

Territorial obstinacy

The last decade witnessed a global economic crisis with unbalancing effects in national and regional economies. Despite the importance of territorial capabilities to face adversity, the “territory” seems to be fading away from public policy. That was clear with the implementation of austerity measures that stimulated centralization of financial resources but also with the relevance given to innovation as the main purpose of development, particularly in European Union with the smart specialization rationale. The current issue of Regional Science – Policy and Practice is devoted to a selection of papers presented at the International Conference on Local Development (Faro, Portugal, 2017). This conference was part of the 4th Edition of the Award on Territorial Development, a distinction that intends to call attention on the opportunities of endogenous and bottomup initiatives for territorial development