Data from paper "Global bimodal precipitation seasonality: A systematic overview"

Data used to create sinusoidal functions that approximate month-to-month rainfall patterns on a global scale and are used to find whether locations experience one or two rainfall seasons per year

Diazoxide-mediated insulin suppression in obese men: a dose-response study.

Contains fulltext : 49140.pdf (publisher's version ) (Closed access)BACKGROUND: It has been suggested that diazoxide (DZX)-mediated insulin suppression may be useful to promote weight loss in obese subjects. AIM: To assess the DZX-dose range that is safe to use in obese hyperinsulinaemic men. METHODS: Assessment of DZX efficacy and safety was based on plasma glucose and insulin responses to a standardized 500-kcal breakfast, taken on the sixth day of treatment. Basic information regarding the potential efficacy of DZX treatment was first evaluated in an open-label study in five non-obese men. Subsequently, a double-blind, randomized, placebo-controlled study was performed in 12 obese but otherwise healthy men, comparing placebo treatment with DZX in doses of 50, 75 and 100 mg three times daily for 6 days. RESULTS: In non-obese subjects, DZX 50 mg decreased peak insulin levels by +/-28% and raised peak glucose concentration from 7.1 +/- 0.6 to 7.8 +/- 0.6 mmol/l (p < 0.05). DZX 100 mg reduced peak insulin levels by 45% and caused a rise in peak glucose levels from 7.1 +/- 0.6 to 9.0 +/- 0.9 mmol/l (p < 0.05). In obese men, the 50 and 75 mg doses had no significant effects on glucose or insulin levels. DZX 100 mg reduced the peak insulin levels and insulin area under the curve by +/-20% (p < 0.05) but did not affect fasting or postprandial glucose levels. The relatively limited insulin-suppressive effects in obese subjects were attributed to the low plasma DZX levels that were achieved in this group. For comparable doses, plasma DZX levels were about 30% lower in obese than in non-obese men. Plasma DZX levels were highly dependent on dose (p < 0.001) and body weight (p < 0.001). Ninety-two percent of the total variability in DZX levels was explained by these two parameters. CONCLUSION: DZX-mediated insulin suppression is dose dependent in normal and in obese men. However, the efficacy of DZX is much less in obese than in non-obese subjects. This is attributed to weight-dependent differences in distribution volume that lead to markedly lower plasma DZX levels in obese subjects. Weight-adjusted doses will be needed to achieve biologically effective plasma DZX levels. Extrapolation of the data suggests that effective insulin suppression in obese men will at least require a daily dose of 3.2-4.2 mg/kg

Global Harmonization of Comparator Products for Bioequivalence Studies

Comparator products should be the products that were shown to be safe and efficacious in pivotal clinical trials to ensure prescribability of generics. The use of a common comparator ensures switchability between generics. The selection of the comparator is a national responsibility and may be different between countries. This paper discusses the current recommendations on selection of comparators, the associated problems, and the possibility of harmonization. Most countries follow the World Health Organization (WHO) recommendations for selecting comparator products and require the comparator product to be obtained from their national markets to ensure switchability between the local comparator and their generics. These recommendations are only feasible in the few countries where the repetition of the bioequivalence study is economically feasible, but they are impracticable in all other countries. Furthermore, the exclusive use of the local comparator to ensure switchability is ethically and scientifically questionable. The innovator product from well-regulated markets should be the global comparator. This harmonization is feasible as the concept already applies in the WHO prequalification program. It is ineffectual to harmonize only the requirements for performing bioequivalence studies, if such a study has to be repeated for every single country simply because of the different comparator products

Marginality: From theory to practices

The essay tackles the concept of regional marginality, by presenting the main open fields of discussion regarding: the criteria by which to identify the marginal regions, how to measure marginality and the nature of the dynamics between center and periphery. Focusing on these three aspects, the paper concentrates on the relation between theories and consequent practices. Indeed, it is demonstrated how starting from different ideas it is possible to arrive at completely different hypothesis of actions. The paper aims at providing a critical reading about answers given to these complex questions. What makes a region marginal in respect to another? How to measure and represent this phenomenon? Can the unbalanced relationship between core and periphery change in time? If yes, should public policies try to rebalance such relationship? In which way? In the conclusion, an approach to face the issue of marginality is proposed, in the form of “line-based projects”, in opposition to the traditional “point-based projects”