Dendrochronology and Deer Park Farms

This chapter examines some aspects of the environmental
context for the constructional activity observed at Deer
Park Farms (DPF). This can be done at several levels by
observing what dendrochronology suggests in terms of
environment and environmental change across the period
from around AD 500 to 1000. Looking at the broad sweep
of tree growth across the period, something not previously
attempted, we can make comparisons between tree
growth in Ireland and elsewhere in Europe. We can study
abrupt events in the records and draw on information
from other sources in an attempt to paint a picture of the
period against which to view the constructional activity
on the site itself. It is worth remarking that there is no
blueprint for this work. Most of the information used has
only recently been produced and it is largely independent
of conventional history.

Transmission Potential of Rift Valley Fever virus over the course of the 2010 epidemic in South Africa

A Rift Valley fever (RVF) epidemic affecting animals on domestic livestock farms was reported in South Africa during January-August 2010. The first cases occurred after heavy rainfall, and the virus subsequently spread countrywide. To determine the possible effect of environmental conditions and vaccination on RVF virus transmissibility, we estimated the effective reproduction number (R) for the virus over the course of the epidemic by extending the Wallinga and Teunis algorithm with spatial information. Re reached its highest value in mid-February and fell below unity around mid-March, when vaccination coverage was 7.5%-45.7% and vector-suitable environmental conditions were maintained. The epidemic fade-out likely resulted first from the immunization of animals following natural infection or vaccination. The decline in vector-suitable environmental conditions from April onwards and further vaccination helped maintain R below unity. Increased availability of vaccine use data would enable evaluation of the effect of RVF vaccination campaigns.

Evaluation of the antidiabetic activity of DPP IV resistant N-terminally modified versus mid-chain acylated analogues of glucose-dependent insulinotropic polypeptide

Glucose dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone with therapeutic potential for type 2 diabetes due to its insulin-releasing and antihyperglycaemic actions. However, development of GIP-based therapies is limited by N-terminal degradation by DPP IV resulting in a very short circulating half-life. Numerous GIP analogues have now been generated exhibiting DPP IV resistance and extended bioactivity profiles. In this study, we report a direct comparison of the long-term antidiabetic actions of three such GIP molecules, N-AcGIP, GIP(LyS(37)PAL) and N-AcGIP(LyS(37)PAL) in obese diabetic (ob/ob) mice. An extended duration of action of each GIP analogue was demonstrated prior to examining the effects of once daily injections (25 nmol kg(-1) body weight) over a 14-day period. Administration of either N-AcGIP, GIP(LyS(37)PAL) or N-AcGIP(LyS37PAL) significantly decreased non-fasting plasma glucose and improved glucose tolerance compared to saline treated controls. All three analogues significantly enhanced glucose and nutrient-induced insulin release, and improved insulin sensitivity. The metabolic and insulin secretory responses to native GIP were also enhanced in 14-day analogue treated mice, revealing no evidence of GIP-receptor desensitization. These effects were accompanied by significantly enhanced pancreatic insulin following N-AcGIP(Lys(37)PAL) and increased islet number and islet size in all three groups. Body weight, food intake and circulating glucagon were unchanged. These data demonstrate the therapeutic potential of once daily injection of enzyme resistant GIP analogues and indicate that N-AcGIP is equally as effective as related palmitate derivatised analogues of GIP. (c) 2006 Elsevier Inc. All rights reserved.

A novel, long-acting agonist of glucose-dependent insulinotropic polypeptide suitable for once-daily administration in type 2 diabetes

Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone with a potentially therapeutic role in type 2 diabetes. Rapid degradation by dipeptidylpeptidase IV has prompted the development of enzyme-resistant N-terminally modified analogs, but renal clearance still limits in vivo bioactivity. In this study, we report long-term antidiabetic effects of a novel, N-terminally protected, fatty acid-derivatized analog of GIP, N-AcGIP(LysPAL(37)), in obese diabetic (ob/ob) mice. Once-daily injections of N-AcGIP(LysPAL(37)) over a 14-day period significantly decreased plasma glucose, glycated hemoglobin, and improved glucose tolerance compared with ob/ob mice treated with saline or native GIP. Plasma insulin and pancreatic insulin content were significantly increased by N-AcGIP(LysPAL(37)). This was accompanied by a significant enhancement in the insulin response to glucose together with a notable improvement of insulin sensitivity. No evidence was found for GIP receptor desensitization and the metabolic effects of NAcGIP(LysPAL(37)) were independent of any change in feeding or body weight. Similar daily injections of native GIP did not affect any of the parameters measured. These data demonstrate the ability of once-daily injections of N-terminally modified, fatty acid-derivatized analogs of GIP, such as N-AcGIP(LysPAL(37)), to improve diabetes control and to offer a new class of agents for the treatment of type 2 diabetes.

Behavioural and histopathological analyses of ibuprofen treatment on the effect of aggregated AB (1-42) injections in the rat

It has been suggested that inflammatory processes may play a role in the development of Alzheimerâ??s disease (AD), and that nonsteroidal anti-inflammatory drug treatments may provide protection against the onset of AD. In the current study male Wistar rats were trained in two-lever operant chambers under an alternating lever cyclic-ratio ratio (ALCR) schedule. When responding showed no trends, subjects were divided into groups. One group was bilaterally injected into the CA3 area of the hippocampus with 5 μl of aggregated β-amyloid (Aβ) suspension, and one group was bilaterally injected into the CA3 area of the hippocampus with 5 μl of sterile saline. Subgroups were treated twice daily with 0.1 ml (40 mg/kg) ibuprofen administered orally. The results indicated that chronic administration of ibuprofen protected against detrimental behavioural effects following aggregated Aβ injections. Withdrawal of ibuprofen treatment from aggregated Aβ-injected subjects produced a decline in behavioural performance to the level of the non-treated aggregated Aβ-injected group. Ibuprofen treatment reduced the numbers of reactive astrocytes following aggregated Aβ injection, and withdrawal of ibuprofen resulted in an increase of reactive astrocytes. These results suggest that induced inflammatory processes may play a role in AD, and that ibuprofen treatment may protect against some of the symptoms seen in AD.

Time for treating bone fracture using rhBMP-2: a randomised placebo controlled mouse fracture trial.

Although the mechanisms of osteoinduction by bone morphogenic proteins (BMPs) are increasingly understood, the most appropriate time to administer BMPs exogenously is yet to be clarified.The purpose of this study was to investigate when BMP may be administered to a fracture arena to maximise the enhancement of healing.Forty mice with externally fixed left femoral fractures were randomised into four groups: Group I, the control group was given a placebo of 30 ll saline at day 0; Groups II, III and IV were given 30 ll saline plus 2.5 lg rhBMP-2, at post-operative days 0, 4 or 8, respectively.Sequential radiographs were taken at days 0, 8, 16.On day 22 the mice were sacrificed and both femora were harvested for biomechanical assessment in 3-point bending and histological evaluation.Radiographic analysis indicated that healing of fractures in Groups II and III was significantly greater (p <0.05) than those in Groups I and IV, at both 16 and 22 days post-fracture. The highest median bone mineral content at the fracture site was evidenced in Group III and II.Furthermore, Group III also had the highest relative ultimate load values, followed by Groups II, IV and I.Greater percentage peak loads were observed between Group I and both Groups II and III (p <0.05). Histological examination confirmed that at 22 days post-fracture, only fractures in Groups II and III had united with woven bone, and Groups I and IV still had considerable amounts of fibrous tissue and cartilage at the fracture gap.Data presented herein indicates that there is a time after fracture when rhBMP administration is most effective, and this may be at the time of surgery as well as in the early fracture healing phases.

Synthetic peptides interacting with the 67-kd laminin receptor can reduce retinal ischemia and inhibit hypoxia-induced retinal neovascularization.

The high-affinity 67-kd laminin receptor (67LR) is expressed by proliferating endothelial cells during retinal neovascularization. The role of 67LR has been further examined experimentally by administration of selective 67LR agonists and antagonists in a murine model of proliferative retinopathy. These synthetic 67LR ligands have been previously shown to stimulate or inhibit endothelial cell motility in vitro without any direct effect on proliferation. In the present study, a fluorescently labeled 67LR antagonist (EGF33–42) was injected intraperitoneally into mice and its distribution in the retina was assessed by confocal scanning laser microscopy. Within 2 hours this peptide was localized to the retinal vasculature, including preretinal neovascular complexes, and a significant amount had crossed the blood retinal barrier. For up to 24 hours postinjection, the peptide was still present in the retinal vascular walls and, to a lesser extent, in the neural retina. Non-labeled EGF33–42 significantly inhibited pre-retinal neovascularization in comparison to controls treated with phosphate-buffered saline or scrambled peptide (P <0.0001). The agonist peptide (Lamß1925–933) also significantly inhibited proliferative retinopathy; however, it caused a concomitant reduction in retinal ischemia in this model by promoting significant revascularization of the central retina (P <0.001). Thus, 67LR appears to be an important target receptor for the modulation of retinal neovascularization. Agonism of this receptor may be valuable in reducing the hypoxia-stimulated release of angiogenic growth factors which drives retinal angiogenesis.

The resistance of polyvinylpyrrolidone–Iodine–poly(e-caprolactone) blends to adherence of Escherichia coli

In this study, the resistance of biodegradable biomaterials, composed of blends of poly(e-caprolactone) (PCL) and the polymeric antimicrobial complex, polyvinylpyrrolidone–iodine (PVP-I) to the adherence of a clinical isolate of Escherichia coli is described. Blends of PCL composed of a range of high (50,000 g mol1) to low (5000 g mol1) molecular weight ratios of polymer and either
devoid of or containing PVP-I (1% w/w) were prepared by solvent evaporation. Following incubation (4 h), there was no relationship between m. wt. ratio of PCL in ?lms devoid of PVP-I and adherence ofE. coli. Conversely, microbial adherence to PCL containing PVP-I decreased as the ratio of high:low m. wt. polymer was decreased and was approximately 1000 fold lower than that to comparator ?lms devoid of PVP-I. Following periods of immersion of PVP-I containing PCL ?lms under sink conditions in phosphate buffered saline, subsequent adherence of E. coli was substantially reduced for 2 days (40:60 m. wt. ratio) and 6 days (100:0 m. wt. ratio). Concurrent exposure of PCL and E. coli to sub-minimum inhibitory concentrations (sub-MIC) of PVP-I signi?cantly reduced microbial adherence to the biomaterial; however, the molecular weight ratio of PCL did not affect this outcome. Pretreatment of PCL with similar sub-MIC of PVP-I prior to inclusion within the microbial adherence assay signi?cantly decreased the subsequent adherence of E. coli. Greatest reduction in adherence was observed following treatment of PCL (40:60 m. wt. ratio) with 0.0156% w/w PVP-I. In conclusion, this study has illustrated the utility of PVP-I as a suitable therapeutic agent for incorporation within PCL as a novel biomaterial. Due to the combined antimicrobial and biodegradable properties, these biomaterials offer a promising strategy for the reduction in medical device related infection. © 2004 Elsevier Ltd. All rights reserved.

Characterisation and evaluation of novel surfactant bacterial anti-adherent coatings for endotracheal tubes designed for the prevention of ventilator-associated pneumonia.

It is accepted that ventilator-associated pneumonia is a frequent cause of morbidity and mortality in intensive care patients. This study describes the physicochemical properties of novel surfactant coatings of the endotracheal tube and the resistance to microbial adherence of surfactant coated endotracheal tube polyvinylchloride (PVC). Organic solutions of surfactants containing a range of ratios of cholesterol and lecithin (0:100, 25:75, 50:50, 75:25, dissolved in dichloromethane) were prepared and coated onto endotracheal tube PVC using a multiple dip-coating process. Using modulated temperature differential scanning calorimetry it was confirmed that the binary surfactant systems existed as physical mixtures. The surface properties of both surfactant-coated and uncoated PVC, following treatment with either pooled human saliva or phosphate-buffered saline (PBS), were characterised using dynamic contact angle analysis. Following treatment with saliva, the contact angles of PVC decreased; however, those of the coated biomaterials were unaffected, indicating different rates and extents of macromolecular adsorption from saliva onto the coated and uncoated PVC. The advancing and receding contact angles of the surfactant-coated PVC were unaffected by sonication, thereby providing evidence of the durability of the coatings. The cell surface hydrophobicity and zeta potentials of isolates of Staphylococcus aureus and Pseudomonas aeruginosa, following treatment with either saliva or PBS, and their adherence to uncoated and surfactant-coated PVC (that had been pre-treated with saliva) were examined. Adherence of S. aureus and Ps. aeruginosa to surfactant-coated PVC at each successive time period (0.5, 1, 2, 4, 8 h) was significantly lower than to uncoated PVC, the extent of the reduction frequently exceeding 90%. Interestingly, the microbial anti-adherent properties of the coatings were dependent on the lecithin content. Based on the impressive microbial anti-adherence properties and durability of the surfactant coating on PVC following dip coatings, it is proposed that these systems may usefully reduce the incidence of ventilator-associated pneumonia when employed as luminal coatings of the endotracheal tube.

Eradication of endotracheal tube biofilm by nebulised gentamicin.

Objective: To compare the efficacy of gentamicin, nebulised via the endotracheal tube (ET), with that of parenteral cefotaxime or parenteral cefuroxime in preventing the formation of ET biofilm.

Setting: General intensive care units in two university teaching hospitals.

Design: The microbiology of ET biofilm from 36 ICU patients eligible to receive antibiotic prophylaxis was examined. Peak and trough tracheal concentrations of gentamicin, cefotaxime or cefuroxime were measured in each patient group, on the 2nd day of intubation.

Patients: Twelve patients received gentamicin (80 mg) nebulised in 4 ml normal saline every 8 h, 12 cefotaxime (1 g, 12 hourly) and 12 cefuroxime (750 mg, 8 hourly). Prophylaxis was continued for the duration of intubation.

Measurements and results: Samples of tracheal secretions were taken on the 2nd day of ventilation for determination of antibiotic concentrations. Following extubation, ETs were examined for the presence of biofilm. Pathogens considered to be common aetiological agents for VAP included Staphylococcus aureus, enterococci, Enterobacteriaceae and pseudomonads. While microbial biofilm was found on all ETs from the cephalosporin group, microbial biofilm of these micro-organisms was found on 7 of the 12 ET tubes from patients receiving cefotaxime [S. aureus (4), pseudomonads (1), Enterobacteriaceae (1), enterococcus (1)] and 8 of the 12 ET tubes from patients receiving cefuroxime [Enterobacteriaceae (6), P. aeruginosa (1) and enterococcus (1)]. While microbial biofilm was observed on five ETs from patients receiving nebulised gentamicin, none of these were from pathogens for ventilator-associated pneumonia (VAP). Tracheal concentrations of both cephalosporins were lower than those needed to inhibit the growth of pathogens recovered from ET tube biofilm. The median (and range) concentrations for cefotaxime were 0.90 (<0.23–1.31) mg/l and 0.28 (<0.23–0.58) mg/l for 2 h post-dose and trough samples, respectively. Two hours post-dose concentrations of cefuroxime (median and range) were 0.40 (0.34–0.83) mg/l, with trough concentrations of 0.35 (<0.22–0.47) mg/l. Tracheal concentrations (median and range) of gentamicin measured 1 h post-nebulisation were 790 (352–>1250) mg/l and then, before the next dose, were 436 (250–1000) mg/l.

Conclusion: Nebulised gentamicin attained high concentrations in the ET lumen and was more effective in preventing the formation of biofilm than either parenterally administered cephalosporin and therefore may be effective in preventing this complication of mechanical ventilation.

Safety and Immunogenicity of a Novel Recombinant Subunit Respiratory Syncytial Virus Vaccine (BBG2Na) in Healthy Young Adults

A novel recombinant respiratory syncytial virus (RSV) subunit vaccine, designated BBG2Na, was administered to 108 healthy adults randomly assigned to receive 10, 100, or 300 μg of BBG2Na in aluminum phosphate or saline placebo. Each subject received 1, 2, or 3 intramuscular injections of the assigned dose at monthly intervals. Local and systemic reactions were mild, and no evidence of harmful properties of BBG2Na was reported. The highest ELISA and virus-neutralizing (VN) antibody responses were evident in the 100- and 300-μg groups; second or third injections provided no significant boosts against RSV-derived antigens. BBG2Na induced ⩾2-fold and ⩾4-fold increases in G2Na-specific ELISA units in up to 100% and 57% of subjects, respectively; corresponding RSV-A–specific responses were 89% and 67%. Furthermore, up to 71% of subjects had ⩾2-fold VN titer increases. Antibody responses to 2 murine lung protective epitopes were also highly boosted after vaccination. Therefore, BBG2Na is safe, well tolerated, and highly immunogenic in RSV-seropositive adults

Water quality impacts and palaeohydrogeology in the East Yorkshire Chalk Aquifer, UK

A large hydrochemical data-set for the East Yorkshire Chalk has been assessed. Controls on the distribution of water qualities within this aquifer reflect: water-rock interactions (affecting especially the carbonate system and associated geochemistry); effects of land-use change (especially where the aquifer is unconfined); saline intrusion and aquifer refreshening (including ion exchange effects); and aquifer overexploitation (in the semi-confined and confined zones of the aquifer). Both Sr and I prove useful indicators of groundwater ages, with I/Cl ratios characterising two sources of saline waters. The hydrochemical evidence clearly reveals the importance of both recent management decisions and palaeohydrogeology in determining the evolution and distribution of groundwater salinity within the artesian and confined zones of the aquifer. Waters currently encountered in the aquifer are identified as complex (and potentially dynamic) mixtures between modern recharge waters, modern seawater, and old seawaters which entered the aquifer many millennia ago.

Post-depositional modification of atmospheric dust on a granite building in central Rio de Janeiro: implications for surface induration and subsequent stone decay

Extensive contour scaling of a 200 year old granite church is associated with the breaching of an apparently iron-rich crust and the widespread deposition of atmospheric dust within the canyon-like streetscape of Rio de Janeiro. Contemporary dust, accumulated dust from within the a depression on the building surface, the surface crust and the underlying granite are examined by a combination of total element analysis and sequential extraction, X-ray diffraction and energy dispersive X-ray fluorescence. Results indicate an increase in total organic carbon and a marked decrease in pH within the accumulated dust, and a rapid mobilization of anions and cations from the water-soluble and carbonate phases. It is considered that the latter is linked to salt accumulation within and eventual salt weathering of the granite. Post-depositional alteration of the dust is also linked with the de-silicification of clay minerals (Illite to kaolinite) and the loss of silica from the amorphous Fe/Mn phase of the accumulated dust under the initially saline and progressively more acidic conditions experienced at the stone - atmosphere interface. This mobilization of silica is associated with the formation of what is, in effect, a thin silica-rich surface crust or glaze. Within the glaze, assessory amounts of extractable iron are concentrated within the amorphous and crystalline Fe/Mn phases at levels that are significantly elevated with respect to the underlying granite, but much lower than the equivalent phases of the accumulated dust from which it is principally assumed to derive. The protection afforded to the stone work by the crust is not, however, permanent and within the last 15 years it has been possible to observe a rapid increase in the surface delamination of the church close to street level.