Novel polyvinylpyrrolidones to improve delivery of poorly-water soluble drugs; from design to synthesis and evaluation

Polyvinylpyrrolidone is a widely used in tablet formulations with the linear form acting as a wetting agent and disintegrant whereas the cross-linked form is a super-disintegrant. We have previously reported that simply mixing the commercial cross-linked polymer with ibuprofen disrupted drug crystallinity with consequent improvements in drug dissolution behavior. In this study, we have designed and synthesized novel cross-linking agents containing a range of oligoether moieties which have then be polymerized with vinylpyrrolidone to generate a suite of novel excipients with enhanced hydrogen-bonding capabilities. The polymers have a porous surface and swell in most common solvents and in water; properties which suggest their value as disintegrants. The polymers were evaluated in simple physical mixtures with ibuprofen as a model poorly-water soluble drug. The results show that the novel PVPs induce the drug to become “X-ray amorphous”, which increased dissolution to a greater extent than that seen with commercial cross-linked PVP. The polymers stabilize the amorphous drug with no evidence for recrystallization seen after 20 weeks storage.

The impact of cross-border real estate investment on commercial real estate capitalisation rates

This study examines the impact of foreign real estate investment on the US office market capitalization rates. The geographic unit of analysis is MSA and the time period is 2001-2013. Drawing upon a database of commercial real estate transactions provided by Real Capital Analytics, we model the determinants of market capitalization rates with a particular focus on the significance of the proportion of market transactions involving foreign investors. We have employed several econometric techniques to explore the data, potential estimation biases, and test robustness of the results. The results suggest statistically significant effects of foreign investment across 38 US metro areas. It is estimated that, all else equal, a 100 basis points increase in foreign share of total investment in a US metropolitan office market causes about an 8 basis points decrease in the market cap rate.

Formation of dityrosine cross-links during breadmaking

To establish its significance during commercial breadmaking, dityrosine formation was quantified in flours and doughs of six commercial wheat types at various stages of the Chorleywood Bread Process. Dityrosine was formed mainly during mixing and baking, at the levels of nmol/g dry weight. Good breadmaking flours tended to exhibit higher dityrosine content in the final bread than low quality ones, but no relationship was found for dityrosine as a proportion of flour protein content, indicating that the latter was still a dominant factor in the analysis. There was no correlation between gluten yield of the six wheat types and their typical dityrosine concentrations, suggesting that dityrosine crosslinks were not a determinant factor for gluten formation. Ascorbic acid was found to inhibit dityrosine formation during mixing and proving, and have no significant effect on dityrosine in the final bread. Hydrogen peroxide promoted dityrosine formation, which suggests a radical mechanism involving endogenous peroxidases might be the responsible for dityrosine formation during breadmaking.

Prevalence and determinants of Cryptosporidium spp. infection in smallholder dairy cattle in Iringa and Tanga Regions of Tanzania

The prevalence of Cryptosporidium spp. infection in a cross-sectional study of dairy cattle, from two contrasting dairying regions in Tanzania, were determined by staining smears of faecal samples with the modified Ziehl-Neelsen technique. Of the 1126 faecal samples screened, 19.7% were positive for Cr\yptosporidium spp. The prevalence was lower in Tanga Region than in Iringa Region. The prevalence of affected farms was 20% in Tanga and 21 % in Iringa. In both regions, the probability of detecting Cryptosporidium oocysts in faeces varied with animal class, but these were not consistent in both regions. In Tanga Region, Cryptosporidium oocysts were significantly more likely to be found in the faeces of milking cows. In Iringa Region, the likelihood that cattle had Cryptosporidium-positive faeces declined with age, and milking cattle were significantly less likely to have Cryptosporidium-positive faeces. In this region, 7% of cattle were housed within the family house at night, and this was marginally associated with a higher likelihood that animals had Ctyptosporidium-positive faeces. Our study suggests that even though herd sizes are small, Cryptosporidium spp. are endemic on many Tanzanian smallholder dairy farms. These protozoa may impact on animal health and production, but also on human health, given the close associations between the cattle and their keepers. Further studies are required to assess these risks in more detail, and understand the epidemiology of Cryptosporidium spp. in this management system.

Soilborne fungi and bacteria symbiotically associated with Steinernema spp. acting as biological agents against Fusarium wilt of tomato

An isolate of Gliocladium virens from disease affected soil in a commercial tomato greenhouse proved highly antagonistic to Fusarium oxysporum f.sp. lycopersici, used together with an isolate of the nematophagus fungus Verticillium chlamydosporium. Significant disease control was obtained when young mycelial preparation (on a food-base culture) of the G. virens together with V. chlamydosporium was applied in potting medium. Similar results were observed when a Trichoderma harzianum isolate was treated in combination with the V. chlamydosporium isolate. Most promising, in terms of minimizing the Fusarium wilt of tomato incidence, was also the effect of the bacteria associated with entomopathogenic nematodes (Steinernema spp.), Pseudomonas oryzihabitans and Xenorhabdus nematophilus.

The use of dead-end and cross-flow nanofiltration to purify prebiotic oligosaccharides from reaction mixtures

Nanofiltration (NF) of model sugar solutions and commercial oligosaccharide mixtures were studied in both dead-end and cross-flow modes. Preliminary trials, with a dead-end filtration cell, demonstrated the feasibility of fractionating monosaccharides from disaccharides and oligosaccharides in mixtures, using loose nanofiltration (NF-CA-50, NF-TFC-50) membranes. During the nanofiltration purification of a commercial oligosaccharide mixture, yields of 19% (w w-1) for the monosaccharides and 88% (w w-1) for di, and oligosaccharides were obtained for the NF-TFC-50 membrane after four filtration steps, indicating that removal of the monosaccharides is possible, with only minor losses of the oligosaccharide content of the mixture. The effects of pressure, feed concentration, and filtration temperature were studied in similar experiments carried out in a cross-flow system, in full recycle mode of operation. The rejection rates of the sugar components increased with increasing pressure, and decreased with both increasing total sugar concentration in the feed and increasing temperature. Continuous diafiltration (CD) purification of model sugar solutions and commercial oligosaccharide mixtures using NF-CA-50 (at 25oC) and DS-5-DL (at 60oC) membranes, gave yield values of 14 to 18% for the monosaccharide, 59 to 89% for the disaccharide and 81 to 98% for the trisaccharide present in the feed. The study clearly demonstrates the potential of cross flow nanofiltration in the purification of oligosaccharide mixtures from the contaminant monosaccharides.

The sky is the limit? The determinants and constraints of European airports' commercial revenues

This study investigates the determinants of commercial and retail airport revenues as well as revenues from real estate operations. Cross-sectional OLS, 2SLS and robust regression models of European airports identify a number of significant drivers of airport revenues. Aviation revenues per passenger are mainly determined by the national income per capita in which the airport is located, the percentage of leisure travelers and the size of the airport proxied by total aviation revenues. Main drivers of commercial revenues per passenger include the total number of passengers passing through the airport, the ratio of commercial to total revenues, the national income, the share of domestic and leisure travelers and the total number of flights. These results are in line with previous findings of a negative influence of business travelers on commercial revenues per passenger. We also find that a high amount of retail space per passenger is generally associated with lower commercial revenues per square meter confirming decreasing marginal revenue effects. Real estate revenues per passenger are positively associated with national income per capita at airport location, share of intra-EU passengers and percent delayed flights. Overall, aviation and non-aviation revenues appear to be strongly interlinked, underlining the potential for a comprehensive airport management strategy above and beyond mere cost minimization of the aviation sector.

Risk reduction and diversification in UK commercial property portfolios

The issue of diversification in direct real estate investment portfolios has been widely studied in academic and practitioner literature. Most work, however, has been done using either partially aggregated data or data for small samples of individual properties. This paper reports results from tests of both risk reduction and diversification that use the records of 10,000+ UK properties tracked by Investment Property Databank. It provides, for the first time, robust estimates of the diversification gains attainable given the returns, risks and cross‐correlations across the individual properties available to fund managers. The results quantify the number of assets and amount of money needed to construct both ‘balanced’ and ‘specialist’ property portfolios by direct investment. Target numbers will vary according to the objectives of investors and the degree to which tracking error is tolerated. The top‐level results are consistent with previous work, showing that a large measure of risk reduction can be achieved with portfolios of 30–50 properties, but full diversification of specific risk can only be achieved in very large portfolios. However, the paper extends previous work by demonstrating on a single, large dataset the implications of different methods of calculating risk reduction, and also by showing more disaggregated results relevant to the construction of specialist, sector‐focussed funds.

A critical review of methodologies for measuring rental depreciation applied to UK commercial real estate

Real estate depreciation continues to be a critical issue for investors and the appraisal profession in the UK in the 1990s. Depreciation-sensitive cash flow models have been developed, but there is a real need to develop further empirical methodologies to determine rental depreciation rates for input into these models. Although building quality has been found to be an important explanatory variable in depreciation it is very difficult to incorporate it into such models or to analyse it retrospectively. It is essential to examine previous depreciation research from real estate and economics in the USA and UK to understand the issues in constructing a valid and pragmatic way of calculating rental depreciation. Distinguishing between 'depreciation' and 'obsolescence' is important, and the pattern of depreciation in any study can be influenced by such factors as the type (longitudinal or crosssectional) and timing of the study, and the market state. Longitudinal studies can analyse change more directly than cross-sectional studies. Any methodology for calculating rental depreciation rate should be formulated in the context of such issues as 'censored sample bias', 'lemons' and 'filtering', which have been highlighted in key US literature from the field of economic depreciation. Property depreciation studies in the UK have tended to overlook this literature, however. Although data limitations and constraints reduce the ability of empirical property depreciation work in the UK to consider these issues fully, 'averaging' techniques and ordinary least squares (OLS) regression can both provide a consistent way of calculating rental depreciation rates within a 'cohort' framework.

Sources and spread of thermophilic Campylobacter spp. during partial depopulation of broiler chicken flocks

The practice of partial depopulation or ‘thinning’, i.e. early removal of a proportion of birds from a commercial broiler flock, is a reported risk factor for Campylobacter colonization of residual birds because of the difficulty in maintaining biosecurity during the process. Therefore, the effect of this practice was studied in detail for 51 target flocks, each at a different growing farm belonging to one of seven major poultry companies throughout the United Kingdom. On 21 of these farms, the target flock was already colonized by Campylobacter and at slaughter all cecal samples examined were positive, with a mean of log10 8 cfu / g. A further 27 flocks became positive within 2 – 6 days of the start of thinning and had similarly high levels of cecal carriage at slaughter. Just prior to the thinning process, Campylobacter could be isolated frequently from the farm driveways, transport vehicles, equipment and personnel. Strains from seven such farms on which flocks became colonized after thinning were examined by PFGE typing. The study demonstrated an association between strains occurring at specific sampling sites and those isolated subsequently from the thinned flocks. There were also indications that particular strains had spread from one farm to another, when the farms were jointly company-owned and served by the same bird-catching teams and / or vehicles. The results highlighted the need for better hygiene control in relation to catching equipment and personnel, and more effective cleaning and disinfection of vehicles, and bird-transport crates.

Use of pelleted sericea lespedeza (Lespedeza cuneata) for natural control of coccidia and gastrointestinal nematodes in weaned goats

Infection with Eimeria spp. (coccidia) can be devastating in goats, particularly for young, recently-weaned kids, resulting in diarrhea, dehydration, and even death. Feeding dried sericea lespedeza [SL; Lespedeza cuneata (Dum.-Cours.) G. Don.] to young goats has been reported to reduce the effects of internal parasites, including gastrointestinal nematodes (GIN) but there have been no reports of the effects of feeding this forage on Eimeria spp. in goats. Two confinement feeding experiments were completed on recently-weaned intact bucks (24 Kiko-cross, Exp. 1; 20 Spanish, Exp. 2) to determine effects of SL pellets on an established infection of GIN and coccidia. The bucks were assigned to 1 of 2 (Exp. 1) or 3 (Exp. 2) treatment groups based upon the number of Eimeria spp. oocysts per gram (OPG) of feces. In Exp. 1, the kids were fed 1 of 2 pelleted rations ad libitum; 90% SL leaf meal + 10% of a liquid molasses/lignin binder mix and a commercial pellet with 12% crude protein (CP) and 24% acid detergent fiber (n = 12/treatment group, 2 animals/pen). For Exp. 2, treatment groups were fed 1) 90% SL leaf meal pellets from leaves stored 3 years (n = 7), 2) 90% SL pellets from leaf meal stored less than 6 months, (n = 7), and the commercial pellets (n = 6) ad libitum. For both trials, fecal and blood samples were taken from individual animals every 7 days for 28 days to determine OPG and GIN eggs per gram (EPG) and packed cell volume (PCV), respectively. In Exp. 2, feces were scored for consistency (1 = solid pellets, 5 = slurry) as an indicator of coccidiosis. In Exp. 1, EPG (P < 0.001) and OPG (P < 0.01) were reduced by 78.7 and 96.9%, respectively, 7 days after initiation of feeding in goats on the SL pellet diet compared with animals fed the control pellets. The OPG and EPG remained lower in treatment than control animals until the end of the trial. In Exp. 2, goats fed new and old SL leaf meal pellets had 66.2 and 79.2% lower (P < 0.05) EPG and 92.2 and 91.2% lower (P < 0.05) OPG, respectively, than control animals within 7 days, and these differences were maintained or increased throughout the trial. After 4 weeks of pellet feeding in Exp. 2, fecal scores were lower (P < 0.01) in both SL-fed groups compared with control animals, indicating fewer signs of coccidiosis. There was no effect of diet on PCV values throughout either experiment. Dried, pelleted SL has excellent potential as a natural anti-coccidial feed for weaned goats.

Biomedical applications of hydrogels: a review of patents and commercial products

Hydrogels have become very popular due to their unique properties such as high water content, softness, flexibility and biocompatibility. Natural and synthetic hydrophilic polymers can be physically or chemically cross-linked in order to produce hydrogels. Their resemblance to living tissue opens up many opportunities for applications in biomedical areas. Currently, hydrogels are used for manufacturing contact lenses, hygiene products, tissue engineering scaffolds, drug delivery systems and wound dressings. This review provides an analysis of their main characteristics and biomedical applications. From Wichterle’s pioneering work to the most recent hydrogel-based inventions and products on the market, it provides the reader with a detailed introduction to the topic and perspective on further potential developments.