Scope and Limitations of The Co-Drug Approach to Topical Drug Delivery

Many currently available drugs show unfavourable physicochemical properties for delivery into or across the skin and temporary chemical modulation of the penetrant is one option to achieve improved delivery properties. Pro-drugs are chemical derivatives of an active drug which is covalently bonded to an inactive pro-moiety in order to overcome pharmaceutical and pharmacokinetic barriers. A pro-drug relies upon conversion within the body to release the parent active drug (and pro-moiety) to elicit its pharmacological effect. The main drawback of this approach is that the pro-moiety is essentially an unwanted ballast which, when released, can lead to adverse effects. The term ‘co-drug’ refers to two or more therapeutic compounds active against the same disease bonded via a covalent chemical linkage and it is this approach which is reviewed for the first time in the current article. For topically applied co-drugs, each moiety is liberated in situ, either chemically or enzymatically, once the stratum corneum barrier has been overcome by the co-drug. Advantages include synergistic modulation of the disease process, enhancement of drug delivery and pharmacokinetic properties and the potential to enhance stability by masking of labile functional groups. The amount of published work on co-drugs is limited but the available data suggest the co-drug concept could provide a significant therapeutic improvement in dermatological diseases. However, the applicability of the co-drug approach is subject to strict limitations pertaining mainly to the availability of compatible moieties and physicochemical properties of the overall molecule.

The air distribution index as an indicator for energy consumption and performance of ventilation systems

This paper deals with the energy consumption and the evaluation of the performance of air supply systems for a ventilated room involving high- and low-level supplies. The energy performance assessment is based on the airflow rate, which is related to the fan power consumption by achieving the same environmental quality performance for each case. Four different ventilation systems are considered: wall displacement ventilation, confluent jets ventilation, impinging jet ventilation and a high level mixing ventilation system. The ventilation performance of these systems will be examined by means of achieving the same Air Distribution Index (ADI) for different cases. The widely used high-level supplies require much more fan power than those for low-level supplies for achieving the same value of ADI. In addition, the supply velocity, hence the supply dynamic pressure, for a high-level supply is much larger than for low-level supplies. This further increases the power consumption for high-level supply systems. The paper considers these factors and attempts to provide some guidelines on the difference in the energy consumption associated with high and low level air supply systems. This will be useful information for designers and to the authors' knowledge there is a lack of information available in the literature on this area of room air distribution. The energy performance of the above-mentioned ventilation systems has been evaluated on the basis of the fan power consumed which is related to the airflow rate required to provide equivalent indoor environment. The Air Distribution Index (ADI) is used to evaluate the indoor environment produced in the room by the ventilation strategy being used. The results reveal that mixing ventilation requires the highest fan power and the confluent jets ventilation needs the lowest fan power in order to achieve nearly the same value of ADI.

Isolation, structure, chemistry, and photochemistry of cis-bis(2,2'-bipyridyl)carbonylchlororuthenium(II) perchlorate

The molecular structure and chemical and photochemical reactions of [Ru(bpy)2(CO)Cl]+ClO4–, which has been isolated from the reaction of ruthenium trichloride and 2,2′-bipyridyl(bpy) in dimethylformamide, are described.

The ERA-Interim reanalysis: configuration and performance of the data assimilation system

ERA-Interim is the latest global atmospheric reanalysis produced by the European Centre for Medium-Range Weather Forecasts (ECMWF). The ERA-Interim project was conducted in part to prepare for a new atmospheric reanalysis to replace ERA-40, which will extend back to the early part of the twentieth century. This article describes the forecast model, data assimilation method, and input datasets used to produce ERA-Interim, and discusses the performance of the system. Special emphasis is placed on various difficulties encountered in the production of ERA-40, including the representation of the hydrological cycle, the quality of the stratospheric circulation, and the consistency in time of the reanalysed fields. We provide evidence for substantial improvements in each of these aspects. We also identify areas where further work is needed and describe opportunities and objectives for future reanalysis projects at ECMWF

Host selection and performance of the giant willow aphid, Tuberolachnus salignus (Gmelin) - Implications for pest management

1 The recent increase in planting of selected willow clones as energy crops for biomass production has resulted in a need to understand the relationship between commonly grown, clonally propagated genotypes and their pests. 2 For the first time, we present a study of the interactions of six willow clones and a previously unconsidered pest, the giant willow aphid Tuberolachnus salignus. 3 Tuberolachnus salignus alatae displayed no preference between the clones, but there was genetic variation in resistance between the clones; Q83 was the most resistant and led to the lowest reproductive performance in the aphid 4 Maternal effects buffered changes in aphid performance. On four tested willow clones fecundity of first generation aphids on the new host clone was intermediate to that of the second generation and that of the clone used to maintain the aphids in culture. 5 In the field, patterns of aphid infestation were highly variable between years, with the duration of attack being up to four times longer in 1999. In both years there was a significant effect of willow clone on the intensity of infestation. However, whereas Orm had the lowest intensity of infestation in the first year, Dasyclados supported a lower population level than other monitored clones in the second year.

Effect of inclusion of lactulose and Lactobacillus plantarum on the intestinal environment and performance of piglets at weaning

The prebiotic lactulose, a probiotic strain of Lactobacillus plantarum (L. plantarum) and a synbiotic combination of these two agents were evaluated as growth promoters in 25–39-day old commercial weaning pigs. Ninety-six weaning pigs were allocated into 32 pens, taking initial weight into account, and distributed into four groups as follows: a control diet (CTR), the same diet supplemented daily with L. plantarum (109 CFU/mL sprayed on top; 20 mL/pig) (LPN); 10 g/kg lactulose (LAC) or a combination of both treatments (SYN). At day 14, eight piglets from each group were euthanized and proximal colon digesta was sampled for luminal pH, short-chain fatty acids (SCFA) and lactic acid concentrations. Deoxyribonucleic acid was extracted from colonic digesta and the microbial community was profiled by terminal restriction fragment length polymorphism analysis (T-RFLP) and qPCR. Blood urea nitrogen (BUN) and acute-phase proteins (Pig-MAP) were measured. Lactulose treatment (LAC) improved feed intake (P<0.05), average daily gain (P<0.01), feed:gain ratio (P<0.05) and reduced BUN (P<0.01). Both, LAC and LPN treatment, decreased the Enterobacteriaceae:Lactobacillus spp. ratio in the colonic luminal contents (P<0.05). Moreover LPN treatment promoted a decrease in the percentage of branched fatty acids (P<0.01) suggesting a reduction in proteolytic microbial activity. Microbial profiling of colonic luminal contents by T-RFLP revealed changes in some microbial species. Terminal restriction fragments (TRFs) compatible with Bifidobacterium thermoacidophilum were more frequently detected in experimental diets compared to CTR (P<0.05). Pigs receiving SYN diet demonstrated the combined positive effects of individual LAC and LPN treatment although we were not able to show a specific increase in the probiotic strain with the inclusion of lactulose. Collectively, these data suggest the combination of lactulose and L. plantarum acts as a complementary synbiotic, but not as a synergistic combination.

Authenticity and performance of class in British factual TV series

The chapter characterises British ‘Reality TV’ as a hybrid of factual and fictional television genres, as signaled by the more accurate genre designation ‘structured reality’ television. From the 1990s onwards, in order to develop programmes that are attractive to audiences and inexpensive to produce, programme makers have focused on hybrids of dramatic and documentary modes. This chapter argues that many recent Reality TV programmes privilege soap opera’s emphasis on character, storyline and performance. This affects the ways that class authenticity is understood, undermining factual programmes’ usual claim to legitimacy based on reference to a pre-existing reality, and transforming hierarchies that separate highly-valued from low-valued types of programme.

The dilemma of scope and scale for construction professional service firms

Construction professional service (CPS) firms sell expertise and provide innovative solutions for projects founded on their knowledge, experience, and technical competences. Large CPS firms seeking to grow will often seek new opportunities in their domestic market and overseas by organic or inorganic growth through mergers, alliances, and acquisitions. Growth can also come from increasing market penetration through vertical, horizontal, and lateral diversification. Such growth, hopefully, leads to economies of scope and scale in the long term, but it can also lead to diseconomies, when the added cost of integration and the increased complexity of diversification no longer create tangible and intangible benefits. The aim of this research is to investigate the key influences impacting on the growth in scope and scale for large CPS firms. Qualitative data from the interviews were underpinned by secondary data from CPS firms’ annual reports and analysts’ findings. The findings showed five key influences on the scope and scale of a CPS firm: the importance of growth as a driver; the influence of the ownership of the firm on the decision for growth in scope and scale; the optimization of resources and capabilities; the need to serve changing clients’ needs; and the importance of localization. The research provides valuable insights into the growth strategies of international CPS firms. A major finding of the research is the influence of ownership on CPS firms’ growth strategies which has not been highlighted in previous research.

The use and usefulness of financial assistance to UK SMEs

Existing literature has paid considerable attention to the effects of supporting programmes on the survival and performance of small and medium-sized enterprises (SMEs), but it lacks a deep understanding of the benefits of the use of such assistance and the factors influencing the evaluation of such services from the perspective of SMEs. We examine the factors affecting the propensity to use assistance when SMEs make financial decisions and the usefulness perceived by the users. We examine 2500 UK SMEs and find that the use of assistance and the usefulness of such services, as perceived by SMEs, are much related to: the characteristics of the entrepreneur, the nature of the business, and the financial products used by the business. These empirical results imply that support and advice on financial decision making, available for SMEs, are important for them to better manage and to access finance. Assistance and advice are also very valuable for SMEs and entrepreneurs to compensate for their lack of human capital and thus facilitate overcoming possible problems in managing their businesses.

Governmentality, subject-building, and the discourses and practices of devolution in the UK

This paper uses a Foucauldian governmentality framework to analyse and interrogate the discourses and strategies adopted by the state and sections of the business community in their attempts to shape and influence emerging agendas of governance in post-devolution Scotland. Much of the work on governmentality has examined the ways in which governments have developed particular techniques, rationales and mechanisms to enable the functioning of governance programmes. This paper expands upon such analyses by also looking at the ways in which particular interests may use similar procedures, discourses and practices to promote their own agendas and develop new forms of resistance, contestation and challenge to emerging policy frameworks. Using the example of business interest mobilization in post-devolution Scotland, it is argued that governments may seek to mobilize defined forms of expertise and knowledge, linking them to wider political debates. This, however, creates new opportunities for interests to shape and contest the discourses and practices of government. The governmentalization of politics can, therefore, be seen as more of a dialectical process of definition and contestation than is often apparent in existing Foucault-inspired writing.