Optimal protection of stabilised dry live bacteria from bile toxicity in oral dosage forms by bile acid adsorbent resins

We previously found that dried live bacteria of a vaccine strain can be temporarily sensitive to bile acids and suggested that Bile Adsorbing Resins (BAR) can be used in oral vaccine tablets to protect dried bacteria from intestinal bile. Here, we report a quantitative analysis of the ability of BAR to exclude the dye bromophenol blue from penetrating into matrix tablets and also sections of hard capsule shells. Based on this quantitative analysis, we made a fully optimised formulation, comprising 25% w/w of cholestyramine in Vcaps™ HPMC capsules. This gave effectively 100% protection of viability from 4% bile, with 4200-fold more live bacteria recovered from this formulation compared to unprotected dry bacteria. From the image analysis, we found that the filler material or compaction force used had no measurable effect on dye exclusion but did affect the rate of tablet hydration. Increasing the mass fraction of BAR gave more exclusion of dye up to 25% w/w, after which a plateau was reached and no further dye exclusion was seen. More effective dye exclusion was seen with smaller particle sizes (i.e. cholestyramine) and when the BAR was thoroughly dried and disaggregated. Similar results were found when imaging dye penetration into capsule sections or tablets. The predictions of the dye penetration study were tested using capsules filled with dried attenuated Salmonella vaccine plus different BAR types, and the expected protection from bile was found, validating the imaging study. Surprisingly, depending on the capsule shell material, some protection was given by the capsule alone without adding BAR, with Vcaps™ HPMC capsules providing up to 174-fold protection against 1% bile; faster releasing Vcaps Plus™ HPMC capsules and Coni Snap™ gelatin capsules gave less protection.

Protection of live bacteria from bile acid toxicity using bile acid adsorbing resins

We previously demonstrated that a dry, room temperature stable formulation of a live bacterial vaccine was highly susceptible to bile, and suggested that this will lead to significant loss of viability of any live bacterial formulation released into the intestine using an enteric coating or capsule. We found that bile and acid tolerance is very rapidly recovered after rehydration with buffer or water, raising the possibility that rehydration in the absence of bile prior to release into the intestine might solve the problem of bile toxicity to dried cells. We describe here a novel formulation that combines extensively studied bile acid adsorbent resins with the dried bacteria, to temporarily adsorb bile acids and allow rehydration and recovery of bile resistance of bacteria in the intestine before release. Tablets containing the bile acid adsorbent cholestyramine release 250-fold more live bacteria when dissolved in a bile solution, compared to control tablets without cholestyramine or with a control resin that does not bind bile acids. We propose that a simple enteric coated oral dosage form containing bile acid adsorbent resins will allow improved live bacterial delivery to the intestine via the oral route, a major step towards room temperature stable, easily administered and distributed vaccine pills and other bacterial therapeutics

A tractable means of correcting sector level TFP calculations in the face of biased technological change.

The measurement of the impact of technical change has received significant attention within the economics literature. One popular method of quantifying the impact of technical change is the use of growth accounting index numbers. However, in a recent article Nelson and Pack (1999) criticise the use of such index numbers in situations where technical change is likely to be biased in favour of one or other inputs. In particular they criticise the common approach of applying observed cost shares, as proxies for partial output elasticities, to weight the change in quantities which they claim is only valid under Hicks neutrality. Recent advances in the measurement of product and factor biases of technical change developed by Balcombe et al (2000) provide a relatively straight-forward means of correcting product and factor shares in the face of biased technical progress. This paper demonstrates the correction of both revenue and cost shares used in the construction of a TFP index for UK agriculture over the period 1953 to 2000 using both revenue and cost function share equations appended with stochastic latent variables to capture the bias effect. Technical progress is shown to be biased between both individual input and output groups. Output and input quantity aggregates are then constructed using both observed and corrected share weights and the resulting TFPs are compared. There does appear to be some significant bias in TFP if the effect of biased technical progress is not taken into account when constructing the weights

Measuring productivity growth when technological change is biased - a new index and an application to UK agriculture

Productivity growth is conventionally measured by indices representing discreet approximations of the Divisia TFP index under the assumption that technological change is Hicks-neutral. When this assumption is violated, these indices are no longer meaningful because they conflate the effects of factor accumulation and technological change. We propose a way of adjusting the conventional TFP index that solves this problem. The method adopts a latent variable approach to the measurement of technical change biases that provides a simple means of correcting product and factor shares in the standard Tornqvist-Theil TFP index. An application to UK agriculture over the period 1953-2000 demonstrates that technical progress is strongly biased. The implications of that bias for productivity measurement are shown to be very large, with the conventional TFP index severely underestimating productivity growth. The result is explained primarily by the fact that technological change has favoured the rapidly accumulating factors against labour, the factor leaving the sector. (C) 2004 Elsevier B.V. All rights reserved.

Dual technological development in Botswana agriculture: A Stochastic input distance function approach

To improve the welfare of the rural poor and keep them in the countryside, the government of Botswana has been spending 40% of the value of agricultural GDP on agricultural support services. But can investment make smallholder agriculture prosperous in such adverse conditions? This paper derives an answer by applying a two-output six-input stochastic translog distance function, with inefficiency effects and biased technical change to panel data for the 18 districts and the commercial agricultural sector, from 1979 to 1996 This model demonstrates that herds are the most important input, followed by draft power. land and seeds. Multilateral indices for technical change, technical efficiency and total factor productivity (TFP) show that the technology level of the commercial agricultural sector is more than six times that of traditional agriculture and that the gap has been increasing, due to technological regression in traditional agriculture and modest progress in commercial agriculture. Since the levels of efficiency are similar, the same patient is repeated by the TFP indices. This result highlights the policy dilemma of the trade-off between efficiency and equity objectives.

Nature protection in Greece: an appraisal of the factors shaping integrative conservation and policy effectiveness

The proliferation of designated areas following the implementation of Natura 2000 in Greece has initiated changes in the protected area design and conservation policy making aiming at delivering action for biodiversity and integrative planning on a wider landscape. Following the sustainability concept, an integrative approach cannot realistically take place simply by extending the protected area and designations. The paper addresses public involvement and inter-sectoral coordination as major procedural elements of integrative management and evaluates the nature and strength of their negative or positive influences on the fulfillment of an integrative vision of nature conservation. A review of the history of protected areas and administration developments in Greece provide useful input in the research. The analysis has shown that the selected network of Natura 2000 sites has been superimposed upon the existing system and resulted in duplication of administrative effort and related legislation. As a result the overall picture of protected areas in the country appears complex, confusing and fragmented. Major failures to integrated conservation perspective can be traced to structural causes rooted in politico-economic power structures of mainstream policy and in a rather limited political commitment to conservation. It is concluded that greater realisation. of integrated conservation in Greece necessitates policy reforms related mainly to sectoral legal frameworks to promote environmentalism as well as an increased effort by the managing authorities to facilitate a broader framework of public dialogue and give local communities incentives to sustainably benefit from protected areas. (C) 2006 Elsevier Ltd. All rights reserved.

Plant variety protection in developing countries: A view from the private seed industry in India

Many developing countries are currently engaged in designing and implementing plant variety protection systems. Encouraging private investment in plant breeding is the key rationale for extending intellectual property rights to plant varieties. However, the design of plant variety protection systems in developing countries has been dominated by concerns regarding the inequities of a plant variety protection system, especially the imbalance in the reward structure between plant breeders and farmers. The private seed industry, a key stakeholder in plant variety protection, appears to be playing only a peripheral role in the design of the intellectual property rights regime. This paper explores the potential response of the private seed industry in India to plant variety protection legislation based on a survey of major plant breeding companies. The survey finds that the private seed industry in India is generally unenthusiastic about the legislation and plant variety protection is likely to have only a very limited impact on their research profile and expenditures on plant breeding. Measures designed to curb the 'excessive' profits of breeders, farmers' rights provisions and poor prospects for enforcement of rights are seen to be seriously diluting breeders' rights, leaving few incentives for innovation. If the fundamental objective of plant variety protection is to stimulate private investment in plant breeding, then developing countries need to seriously address the question of improving appropriability of returns from investment.