Autoradiographic and scintillation analysis of 5-aminolevulinic acid permeation through epithelialised tissue: Implications for topical photodynamic therapy of superficial gynaecological neoplasias

Purpose. Aminolevulinic acid (5-ALA) diffusion through both keratinised and non-keratinised tissue, used as a model tissue substrates, was evaluated, together with the depth of permeation and the concentration achieved following delivery from bioadhesive patch and proprietary cream formulations. Materials and Methods. Moisture-activated, bioadhesive patches loaded with 5-ALA at concentrations of 19.0, 38.0 and 50.0 mg cm(-2) and an o/w cream (20% w/w 5-ALA) were radiolabelled with C14 5-ALA and applied to excised human vaginal tissue and porcine skin. After 1, 2 and 4 h, tissue was sectioned in two orientations and the 5-ALA concentration at specific depths determined using autoradiography and liquid scintillation counting (LSC). Results. The stratum corneum was a significant barrier to 5-ALA permeation, with concentrations in tissue dependent on application time and drug loading. 5-ALA was detected at 6 mm using autoradiography after 2 h, with LSC showing phototoxic concentrations at 2.375 mm after 4 h of application. Inclusion of oleic acid and dimethyl sulphoxide in bioadhesive patches increased 5-ALA significantly in neonate porcine tissue, but only for patches cast from blends containing 5% w/w oleic acid. Conclusions. The bioadhesive patch described delivered 5-ALA to depths of at least 2.5 mm in tissue types indicative of vulval skin, suggesting that photodynamic therapy of deep vulval intraepithelial neoplasia is feasible using this means of bioadhesive 5-ALA delivery.

Analysis of the nearshore wave energy resource

Earlier studies have indicated that the gross nearshore wave energy resource is significantly smaller than the gross offshore wave energy resource implying that the deployment of wave energy converters in the nearshore is unlikely to be economic. However, it is argued that the gross wave energy resource is not an appropriate measure for determining the productivity of a wave farm and an alternative measure, the exploitable wave energy resource, is proposed. Calculation of a site's potential using the exploitable wave energy resource is considered superior because it accounts for the directional distribution of the incident waves and the wave energy plant rating that limits the power capture in highly energetic sea-states. A third-generation spectral wave model is used to model the wave transformation from deep water to a nearshore site in a water depth of 10 m. It is shown that energy losses result in a reduction of less than 10% of the net incident wave power. Annual wave data for the North Atlantic coast of Scotland is analysed and indicates that whilst the gross wave energy resource has reduced significantly by the 10 m depth contour, the exploitable wave energy resource is reduced by 7 and 22% for the two sites analysed. This limited reduction in exploitable wave energy resource means that for many exposed coasts, nearshore sites offer similar potential for exploitation of the wave energy resource as offshore sites.

Effect of Free-Fall Height in Water on Performance of Flowable Concrete

Concrete placed under water should be proportioned to flow readily into place with minimum materials separation. Unlike concrete cast for deep tremie seals, the use of concrete in repairs often necessitates some free fall of the mixture through water. Such placement conditions lead to greater risk of water erosion and segregation, and should be addressed in proportioning highly flowable underwater concrete. This paper evaluates the effect of free-fall height (FFH) of concrete through water on resulting in-place properties. Concrete was cast in blocks measuring 0.54 x 0.44 x 1 m with the initial FFH in water ranging between 0.25 and 0.60 m. In-place compressive and splitting tensile strengths, unit weight, and depth of washed-out and sedimentation materials were determined. In total, 24 highly flowable mixtures with slump flows greater than 500 mm were investigated. The evaluated mixtures were prepared with various hydraulic binders, including conventional Type 10 cement, a binary mixture with 10% of silica fume (SF), and a ternary binder incorporating 20% of fly ash (FA) and 6% of SF. The mixtures were proportioned with water-binder ratios (w/b) ranging between 0.41 and 0.47. Test results show that the increase of FFH of fresh concrete in water can greatly decrease the residual strength and significantly increase the thickness of washed out and sedimentation materials. The incorporation of 10% of SF, or 20% of FA and 6% of SF, and the reduction of the w/b from 0.47 to 0.41 can, however, lead to a significant increase in washout resistance and residual strength. A relationship between residual strength and the coupled factor of free-fall drop of concrete in water and washout resistance is established.

Influence of solution viscosity and injection protocol on distribution patterns of jet injectors: Application to photodynamic tumour targeting

Photodynamic therapy of deep or nodular skin tumours is currently limited by the poor tissue penetration of the porphyrin precursor 5-aminolevulinic acid (ALA) and preformed photosensitisers. In this study, we investigated the potential of jet injection to deliver both ALA and a preformed photosensitiser (meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate, TMP) into a defined volume of skin. Initial studies using a model hydrogel showed that as standoff distance is increased, injection depth decreases. As the ejected volume is increased, injection depth increases. It was also shown, for the first time, that, as injection solution viscosity was increased, for a given injection setting and standoff distance, both total depth of jet penetration, L-t, and depth at which the maximum width of the penetration pattern occurred, L-m, decreased progressively. For a standoff distance of zero, the maximum width of the penetration pattern, L-w, increased progressively with increasing viscosity at each of the injection settings. Conversely, when the standoff distance was 2.5 mm, L-w decreased progressively with increasing viscosity. Studies with neonate porcine skin revealed that an injection protocol comprising an 8.98 mPas solution, an arbitrary injection setting of 8 and a standoff distance of zero was capable of delivering photosensitisers to a volume of tissue (L-t of 2.91 mm, L-m of 2.14 mm, L-w of 5. 10 mm) comparable to that occupied by a typical nodular basal cell carcinoma. Both ALA and TMP were successfully delivered using jet injection, with peak tissue concentrations (67.3 mg cm(-3) and 5.6 mg cm(-3), respectively) achieved at a depth of around 1.0 mm and substantial reductions in drug concentration seen at depths below 3.0 mm. Consequently, jet injection may be suitable for selective targeting of ALA or preformed photosensitisers to skin tumours. (c) 2007 Elsevier B.V. All rights reserved.

Efficacy of sod removal in regenerating fen vegetation for the conservation of the marsh fritillary butterfly Euphydryas aurinia, Montiaghs Moss Nature Reserve, County Antrim, Northern Ireland.

The efficacy of ‘sod removal’ as a fenland restoration technique was tested using an experimental approach at Montiaghs Moss Nature Reserve, Northern Ireland, from 2006 to 2008. The site suffered from rank growth of purple moor-grass Molinia caerulea which was out-competing herbaceous species. Soil was removed up to a depth of 15 cm completely denuding vegetation in the experimental plot exposing bare peat. By July 2007, 15.2% of sod-removal areas were revegetated; by October 2008 cover had risen to 64.6%. Of this cover, purple moor-grass accounted for only 9-11% compared to 78- 79% on control plots. Cover of other rank-forming grass species was also significantly reduced. Sod removal significantly increased the cover of species characteristic of fenlands including sedges Carex spp., rushes Juncus spp., marsh pennywort Hydrocotyle vulgaris and lesser spearwort Ranunculus flammula. It seems likely that sod removal, which lowered the surface of the peat, restored minerotrophic conditions and exposed the historical seed bank stimulating regeneration of some fenland specialists and pioneer species; this resulted in significantly higher species richness on sod removal plots than control plots two years after treatment. There was no demonstrable effect of sod removal on abundance of devil’s-bit scabious Succisa pratensis, the larval food plant of the Annex II listed marsh fritillary butterfly Euphydryas aurinia. We recommend that consideration should be given to artificially seeding devil’s-bit scabious soon after sod removal treatment to promote early recolonisation and to increase plant abundance on the site.

Determining Propeller Erosion at the Stern of a Berthing Ship

This paper presents the findings from an experimental investigation in to the nature and extent of the scouring that occurs when a ship berths in front of a perpendicular quay wall within the confines of a harbor. It examines the interaction between the relative position of the quay wall to the central axis of the ship and the influence of angle of the vessel's rudder on the magnitude of the scouring produced. The experimental programme covered a range of sediment sizes, propeller diameters and speeds of rotation and rudder angles. Also, methods for calculating the depth of expected scour are presented in terms of initial semi-empirical equations for the data range under investigation.

Estimation of in situ stresses using anisotropic elasticity and suction measurements

Sampling and specimen preparation produce changes in mean effective stresses and pore water pressures, even with ‘perfect sampling’. The paper takes an existing simplified three-parameter cross-anisotropic elastic model and uses it to model these changes. The required ratio of cross-anisotropic parameters J/3G* can be obtained from standard CIU triaxial tests. If measurements are also made of suctions in unloaded specimens in the laboratory, then a combination of J/3G*, the measured suction, and the effective overburden pressure permits an estimation of the horizontal effective pressure and the K 0 ‘at rest’ coefficient. This can be helpful in numerical modelling that needs to start from in situ conditions, and in planning pressure levels for reconsolidation of clay specimens in the laboratory. Tests were done on Belfast Upper Boulder Clay from a depth of 28 m. Values of horizontal in situ effective stress estimated from these measurements compare favorably with conventional estimates of the ‘at rest’ coefficient K 0 and the overconsolidation ratio. Estimates of horizontal stress in London Clay were made using published data and the results compared with actual measurements. Again reasonable agreement was obtained.

SuperWASP observations of long timescale photometric variations in cataclysmic variables

Aims: We investigated whether the predictions and results of Stanishev et al. (2002, A&A, 394, 625) concerning a possible relationship between eclipse depths in PX And and its retrograde disc precession phase, could be confirmed in long term observations made by SuperWASP. In addition, two further CVs (DQ Her and V795 Her) in the same SuperWASP data set were investigated to see whether evidence of superhump periods and disc precession periods were present and what other, if any, long term periods could be detected. Methods: Long term photometry of PX And, V795 Her and DQ Her was carried out and Lomb-Scargle periodogram analysis undertaken on the resulting light curves. For the two eclipsing CVs, PX And and DQ Her, we analysed the potential variations in the depth of the eclipse with cycle number. Results: The results of our period and eclipse analysis on PX And confirm that the negative superhump period is 0.1417 ± 0.0001d. We find no evidence of positive superhumps in our data suggesting that PX And may have been in a low state during our observations. We improve on existing estimates of the disc precession period and find it to be 4.43 ± 0.05d. Our results confirm the predictions of Stanishev et al. (2002). We find that DQ Her does not appear to show a similar variation for we find no evidence of negative superhumps or of a retrograde disc precession. We also find no evidence of positive superhumps or of a prograde disc precession and we attribute the lack of positive superhumps in DQ Her to be due to the high mass ratio of this CV. We do however find evidence for a modulation of the eclipse depth over a period of 100 days which may be linked with solar-type magnetic cycles which give rise to long term photometric variations. The periodogram analysis for V795 Her detected the likely positive superhump period 0.1165d, however, neither the 0.10826d orbital period nor the prograde 1.53d disc precession period were seen. Here though we have found a variation in the periodogram power function at the positive superhump period, over a period of at least 120 days.

Alasdair MacIntyre and the Hope for a Politics of Virtuous Interdependence

Rebellion, philosophic and political, impels the work of Alasdair MacIntyre. Neither of the left nor the right, he treads a borderline path between conservatism and radicalism in holding to a socialist Thomistic Aristotelianism underpinned by a deliberative ‘ethic of care’ that is implacably opposed to modernity and the advanced capitalist nation-state. The depth of this opposition arouses strong opinions in friend and foe alike. To some he is an eminently dispensable reactionary whose sole consistent feature is an inexplicable ‘hatred of liberal individualism’ (Lessnoff 1999: 4). To others he appears a revolutionary enunciating a departure capable of legitimating the activities of ordinary persons so ‘that previously isolated struggles might be transformed into a new class war of attrition’ (Knight 1996: 896). However, neither interpretation rings true. MacIntyre does develop a cogent critique of the present, but this critique points in directions towards which no politics could hope to move.

Optical coherence tomography is a valuable tool in the study of the effects of microneedle geometry on skin penetration characteristics and in-skin dissolution.

In this study, we used optical coherence tomography (OCT) to extensively investigate, for the first time, the effect that microneedle (MN) geometry (MN height, and MN interspacing) and force of application have upon penetration characteristics of soluble poly(methylvinylether-co-maleic anhydride, PMVE/MA) MN arrays into neonatal porcine skin in vitro. The results from OCT investigations were then used to design optimal and suboptimal MN-based drug delivery systems and evaluate their drug delivery profiles cross full thickness and dermatomed neonatal porcine skin in vitro. It was found that increasing the force used for MN application resulted in a significant increase in the depth of penetration achieved within neonatal porcine skin. For example, MN of 600 µm height penetrated to a depth of 330 µm when inserted at a force of 4.4 N/array, while the penetration increased significantly to a depth of 520 µm, when the force of application was increased to 16.4 N/array. At an application force of 11.0 N/array it was found that, in each case, increasing MN height from 350 to 600 µm to 900 µm led to a significant increase in the depth of MN penetration achieved. Moreover, alteration of MN interspacing had no effect upon depth of penetration achieved, at a constant MN height and force of application. With respect to MN dissolution, an approximate 34% reduction in MN height occurred in the first 15 min, with only 17% of the MN height remaining after a 3-hour period. Across both skin models, there was a significantly greater cumulative amount of theophylline delivered after 24 h from an MN array of 900 µm height (292.23 ± 16.77 µg), in comparison to an MN array of 350 µm height (242.62 ± 14.81 µg) (p < 0.001). Employing full thickness skin significantly reduced drug permeation in both cases. Importantly, this study has highlighted the effect that MN geometry and application force have upon the depth of penetration into skin. While it has been shown that MN height has an important role in the extent of drug delivered across neonatal porcine skin from a soluble MN array, further studies to evaluate the full significance of MN geometry on MN mediated drug delivery are now underway. The successful use of OCT in this study could prove to be a key development for polymeric MN research, accelerating their commercial exploitation.

A commentary on climate change, stone decay dynamics and the ‘greening’ of natural stone buildings: new perspectives on ‘deep wetting’

Environmental controls on stone decay processes are rapidly changing as a result of changing climate. UKCP09 projections for the 2020s (2010–2039) indicate that over much of the UK seasonality of precipitation will increase. Summer dryness and winter wetness are both set to increase, the latter linked to projected precipitation increases in autumn and spring months. If so, this could increase the time that stone structures remain wet and possibly the depth of moisture penetration, and it appears that building stone in Northern Ireland has already responded through an increased incidence of algal ‘greening’.This paper highlights the need for understanding the effects of climate change through a series of studies of largely sandstone structures. Current and projected climatic trends are therefore considered to have aesthetic, physical and chemical implications that are not currently built into our models of sandstone decay, especially with respect to the role played by deep-seated wetness on sandstone deterioration and decay progression and the feedbacks associated with, for example surface algal growth. In particular,it is proposed that algal biofilms will aid moisture retention and further facilitate moisture and dissolved salt penetration to depth. Thus, whilst the outer surface of stone may continue to experience frequent wetting and drying associated with individual precipitation events, the latter is less likely to be complete, and the interiors of building blocks may only experience wetting/drying in response to seasonal cycling. A possible consequence of deeper salt penetration could be a delay in the onset of surface deterioration,but more rapid and effective retreat once it commences as decay mechanisms ‘tap into a reservoir of deep salt’.

Evaluation of effective groundwater recharge of freshwater lens in small islands by the combined modeling of geoelectrical data and water heads

In small islands, a freshwater lens can develop due to the recharge induced by rain. Magnitude and spatial distribution of this recharge control the elevation of freshwater and the depth of its interface with salt water. Therefore, the study of lens morphology gives useful information on both the recharge and water uptake due to evapotranspiration by vegetation. Electrical resistivity tomography was applied on a small coral reef island, giving relevant information on the lens structure. Variable density groundwater flow models were then applied to simulate freshwater behavior. Cross validation of the geoelectrical model and the groundwater model showed that recharge exceeds water uptake in dunes with little vegetation, allowing the lens to develop. Conversely, in the low-lying and densely vegetated sectors, where water uptake exceeds recharge, the lens cannot develop and seawater intrusion occurs. This combined modeling method constitutes an original approach to evaluate effective groundwater recharge in such environments.
[Comte, J.-C., O. Banton, J.-L. Join, and G. Cabioch (2010), Evaluation of effective groundwater recharge of freshwater lens in small islands by the combined modeling of geoelectrical data and water heads, Water Resour. Res., 46, W06601, doi:10.1029/2009WR008058.]

Web crippling behaviour of cold-formed steel channel sections with offset web holes subjected to interior-two-flange loading

Cold-formed steel sections are often used as wall studs or floor joists; such sections often include web holes for ease of installation of the services. Cold-formed steel design codes, however, do not consider the effect of such web holes. In this paper, a combination of experimental tests and non-linear elasto-plastic finite element analyses are used to investigate the effect of such holes on web crippling under interior-two-flange (ITF) loading conditions; the cases of both flange fastened and flange unfastened are considered. A good agreement between the experimental tests and finite element analyses was obtained. The finite element model was then used for the purposes of a parametric study on the effect of different sizes and position of holes in the web. It was demonstrated that the main factors influencing the web crippling strength are the ratio of the hole depth to the depth of the web, and the ratio of the distance from the edge of the bearing to the flat depth of web. Design recommendations in the form of web crippling strength reduction factors are proposed, that are conservative to both the experimental and finite element results.

Behaviour of Brent geese Branta bernicla hrota and wigeon Anas penelope feeding on intertidal Zostera spp

Mixed flocks of pale-bellied Brent geese (Branta bernicla hrota) and wigeon (Anas penelope L.) feeding on intertidal Zostera spp were studied during October 1993 with respect to tidal position, feeding method and duration, and competitive: interactions within and between species. Owing to many disturbance incidents affecting the use of the site by wildfowl, only complete data on flow tides were presented. Brent geese fed over a greater period of the tidal cycle than wigeon. Differences in feeding methods indicated that Brent geese exploited the rhizomes, which are energetically more profitable than the shoot on which wigeon fed. Aggressive interactions were recorded within species but there were no records of aggression between species. More subtle competition for space, however, may have occurred during feeding. Brent geese could reach Zostera spp For a short period after increasing depth of water prevented access by wigeon. However, individual wigeon were observed foraging near feeding Brent geese, picking up the scraps oi material discarded by the latter, and small numbers of wigeon may benefit from the presence of the geese. These benefits for some individual wigeon are not considered to compensate for the disadvantages to the latter species population as a whole in feeding on poorer-quality food for a shorter period of the tidal cycle. This disadvantage is likely to have contributed to the decline in the wigeon population on Strangford Lough, Co. Down, while numbers of Brent geese have been maintained at a high level.

Effectiveness of in situ moisture preconditioning methods for concrete

With greater emphasis now being placed on the durability of concrete and the need for on-site characterization of concrete for durability, there is an increasing dependence on the measurement of the permeation properties of concrete. Such properties can be measured in the laboratory under controlled ambient conditions, namely, temperature and relative humidity, and comparisons made between samples not affected by testing conditions. An important factor that influences permeation measurements is the moisture state of the concrete prior to testing. Moisture gradients are known to exist in exposed concretes; therefore, all laboratory tests are generally carried out after preconditioning to a reference moisture state. This is reasonably easy to achieve in the laboratory, but more difficult to carry out on-site. Different methods of surface preconditioning in situ concrete are available; however, there is no general agreement on the suitability of any one method. Therefore, a comprehensive set of experiments was carried out with four different preconditioning methods. Results from these investigations indicated that only superficial drying could be achieved by using any of the preconditioning methods investigated and that significant moisture movement below a depth of 15 mm was not evident.