A major challenge in oral drug delivery is the development of novel dosage forms to promote absorption of poorly permeable Class III drugs across the intestinal epithelium.To date, no absorption promoter has been approved in a formulation specifically designed for oral delivery of Class III molecules. Promoters that are designated safe for human consumption have been licensed for use in a recently approved buccal insulin spray delivery system and also for many years as part of an ampicillin rectal suppository.Unlike buccal and rectal delivery, oral formulations containing absorption promoters have the additional technical hurdle whereby the promoter and payload must be coreleased in high concentrations at the small intestinal epithelium in order to generate significant but rapidly reversible increases in permeability. The most advanced promoter in the clinic is the medium chain fatty acid (MCFA), sodium caprate (C 10 ) , a compound already approved as a direct food additive. We discuss how it has evolved to a matrix tablet format suitable for administration to humans under the headings of mechanism of action at the cellular and tissue level and in vitro and in vivo efficacy and safety studies.In specific clinical examples, we review how C 10 -based formulations are being tested for oral delivery of bisphosphonates using Gastro Intestinal Permeation Enhancement Technology, GIPET® (Merrion Pharmaceuticals, Ireland) and in a related solid dose format for anti-sense oligonucleotides (ISIS Pharmaceuticals, USA).Keywords: Oral drug delivery, Sodium caprate (C 10 ), absorption promoter, drug delivery platforms, clinical trials, oral formulation, drug delivery systems.3 TJs form a barrier to the uncontrolled absorption of noxious luminal antigens (gate function), and maintain epithelial polarity (fence function) [8,9]. In general, the TJ consists of a restrictive pathway (shunt) with a sharp molecular size cut off, and a second unrestrictive pathway (small pore) that permits paracellular permeation of molecules of radii <4.0 Å [10,11]. Depending on the intestinal region, TJ pore sizes range from 6-22Å, sufficient to permit mannitol (6.7 Å) and EDTA (10.8 Å) to permeate to an extent, whereas the passage of inulin (30-40 Å) and fluorescent-dextran 4kDa (FD-4, 26 Å) is essentially impeded [12][13][14][15][16].A number of approaches have been used to promote oral delivery of Class III drugs ( Alternatively, the use of nanoparticles comprising biocompatible polymers (e.g. chitosan,polylactide-co-glycolide, starch and glucans) can protect cargoes from GI proteases, increase GI retention and promote absorption across gut associated lymphoid tissue (GALT) and to a lesser extent, enterocytes [45][46][47]. Most data on nanoparticle absorption from rodent models suggest that M cells in the follicle-associated epithelium of Peyer's patches (PP) are the favored site of uptake for particles of diameter 500nm-1000nm [45].Given the paucity of M cells in the GI tract of adults, the relevance of PP uptake remains controversial ...

Abstract• Context This review paper provides an overview of approaches to which we may resort for handling the complex decision problems involving uncertainty and risk that climate change implies for forest managers. Modelling approaches that could support adaptive management strategies seem to be called for, not only as climate change denotes increased economic uncertainty but also because new and more reliable information becomes available as time passes and climate changes.• Aims The paper (1) provides a broad overview of state-ofthe-art methods for optimal decision making under risk and uncertainty in forestry and (2) elaborates on the possible use of these methods in adaptive forest management under climate change.

Microcontainers with an inner diameter of 223 µm are fabricated using the polymer SU-8, and evaluated in vitro, in situ and in vivo for their application as an advanced oral drug delivery system for the poorly water soluble drug furosemide. An amorphous sodium salt of furosemide (ASSF) is filled into the microcontainers followed by applying a lid using Eudragit L100. It is possible to control the drug release in vitro, and in vitro absorption studies show that the microcontainers are not a hindrance for absorption of ASSF. In situ perfusion studies in rats are performed with ASSF-filled microcontainers coated with Eudragit and compared to a furosemide solution. The absorption rate constant of ASSF confined in microcontainers is found to be significantly different from the solution, and by light microscopy, it is observed that the microcontainers are engulfed by the intestinal mucus. An oral bioavailability study in rats is performed with ASSF confined in microcontainers coated with Eudragit and a control group with ASSF in Eudragit-coated capsules. A relative bioavailability of 220% for the ASSF in microcontainers compared to ASSF in capsules is found. These studies indicate that the microcontainers could serve as a promising oral drug delivery system.

This paper is concerned with the empirical relationship between biodiversity conservation values and income. We use random effects panel models to examine the effects of income, and then GDP per capita, on willingness to pay for habitat and biodiversity conservation. In a meta-analysis, 145 Willingness To Pay estimates for biodiversity conservation where existence value plays a major role were collected from 46 contingent valuation studies across six continents. Other effects included in the meta-analysis were the study year; habitat type; continent; scope as presented to respondents; whether WTP bids were for preventing a deterioration or gaining an improvement in conservation, whether a specific species or specific habitat was protected; whether the questionnaire used a dichotomous choice or an open-ended format; distribution format; and the choice of payment vehicle. GDP per capita seemed to perform as well as an explanatory variable as respondent's mean stated income, indicating that it is wealth in society as a whole which determines variations in WTP. Our main conclusion is that the demand for biodiversity conservation rises with a nation's wealth, but the income elasticity of demand is less than one. JEL Codes: Q2, H4, D6

Aim of study: We aim at (i) developing a reference definition of mixed forests in order to harmonize comparative research in mixed forests and (ii) review the research perspectives in mixed forests.Area of study: The definition is developed in Europe but can be tested worldwide.Material and Methods: Review of existent definitions of mixed forests based and literature review encompassing dynamics, management and economic valuation of mixed forests.Main results: A mixed forest is defined as a forest unit, excluding linear formations, where at least two tree species coexist at any developmental stage, sharing common resources (light, water, and/or soil nutrients). The presence of each of the component species is normally quantified as a proportion of the number of stems or of basal area, although volume, biomass or canopy cover as well as proportions by occupied stand area may be used for specific objectives. A variety of structures and patterns of mixtures can occur, and the interactions between the component species and their relative proportions may change over time.The research perspectives identified are (i) species interactions and responses to hazards, (ii) the concept of maximum density in mixed forests, (iii) conversion of monocultures to mixed-species forest and (iv) economic valuation of ecosystem services provided by mixed forests.Research highlights: The definition is considered a high-level one which encompasses previous attempts to define mixed forests. Current fields of research indicate that gradient studies, experimental design approaches, and model simulations are key topics providing new research opportunities.Keywords: COST Action; EuMIXFOR; mixed-species forests; admixtures of species.