A Farmer Friendly Feed Budget Calculator for Grazing Management Decisions in Winter and Spring

The Western Australian (WA) environment is Mediterranean with annual legume/grass pastures and a 6 month growing season. In autumn where over grazing can impact pasture establishment and in spring, prior to senescence, when under grazing can mean significant losses of efficiency are crucial times for grazing management. Pasture utilisation is typically low (25-35%) due to conservative stocking regimes; key to increasing productivity is increasing pasture utilisation (Grimm, 1998). Increased levels of productivity require farmer sophistication in the way they feed budget. To this end, satellite technology is being used to provide farmers in southern Australia with weekly estimates of pasture growth rate (PGR; kg DM/ha/d) and monthly estimates of Feed on Offer (FOO; kg DM/ha) (Kelly et al., 2003). In addition the Green Feed Budget Paddock Calculator (GFBC) was developed to provide a simple and accessible electronic calculator, which utilises this new information to assist farmers to feed budget and to make more accurate and timely stocking rate decisions

Evaluation of dental therapists undertaking dental examinations in a school setting in Scotland

Objective: To measure agreement between dental therapists and the Scottish gold-standard dentist undertaking National Dental Inspection Programme (NDIP) examinations. Methods: A study of interexaminer agreement between 19 dental therapists and the national gold-standard dentist was carried out. Pre-calibration training used the caries diagnostic criteria and examination techniques agreed by the British Association for the Study of Community Dentistry (BASCD). Twenty-three 5-year-old children (Primary 1) and 17 11-year-old children (Primary 7) children were examined. Agreement was assessed using kappa statistics on d 3 mft and D 3 MFT for P1 and P7 children, sensitivity and specificity values, and kappa statistics on d 3 t/D 3 T and ft/FT. Calibration data on P1 and P7 children from 2009–2012 involving dentists as examiners were used for comparison. Economic evaluation was undertaken using a cost minimization analysis approach. Results: The mean kappa score was 0.84 (SD 0.07) ranging from 0.69 to 0.94. All dental therapists scored good or very good agreement with the gold-standard dentist. This compares with historic NDIP calibration data with dentists, against the same gold-standard dentist, where the mean kappa value was 0.68 (SD 0.22) with a range of 0.35-1.00. The mean sensitivity score was 0.98 (SD 0.04) (range 0.88-1.0) and mean specificity score was 0.90 (SD 0.06) (range 0.78-0.96). Health economic analysis estimated that salary costs would be 33.6% lower if dental therapists were substituted for dentists in the year 2013, with an estimated saving of approximately £103 646 per annum on the national budget. Conclusion: We conclude that dental therapists show a high level of interexaminer agreement, and with the appropriate annual training and calibration, they could undertake dental examinations as part of the NDIP programme

Genetic polymorphisms between altruism and selfishness close to the Hamilton threshold rb = c

Genes that in certain conditions make their carriers altruistic are being identified, and altruism and selfishness have been shown to be heritable in man. This raises the possibility that genetic polymorphisms for altruism/selfishness exist in man and other animals. Here we characterise some of the conditions in which genetic polymorphisms may occur. We show for dominant or recessive alleles how the positions of stable equilibria depend on the benefit to the recipient, b, and the cost to the altruist, c, for diploid altruists helping half or full sibs, and haplodiploid altruists helping sisters. Stable polymorphisms always occur close to the Hamilton threshold rb = c. The position of the stable equilibrium moves away 0 or 1 with both increases in c, the cost paid by the altruist, and increasing divergence from the Hamilton threshold, and alleles for selfishness can reach frequencies around 50%. We evaluate quantitative estimates of b, c and r from field studies in the light of these predictions, but the values do not fall in the regions where genetic polymorphisms are expected. Nevertheless it will be interesting to see as genes for altruism are discovered whether they are accompanied by alternate alleles for selfishness

Enhancement of methyl-aminolevulinate photodynamic therapy by iron chelation with CP94: an in vitro investigation and clinical dose-escalating safety study for the treatment of nodular basal cell carcinoma.

Clinical TrialAuthor version of article. The final publication is available at Springer via: http://dx.doi.org/10.1007/s00432-008-0358-6PURPOSE: Methyl-aminolevulinate (MAL) photodynamic therapy (PDT) is a cancer therapy that combines the selective accumulation of a photosensitizer in tumor tissue with visible light (and tissue oxygen) to produce reactive oxygen species. This results in cellular damage and ablation of tumor tissue. Combining iron chelators with MAL has the potential to increase the accumulation of the photosensitizer protoporphyrin IX (PpIX) by reducing its bioconversion to heme. This paper investigates this method of enhancement both in vitro and for the first time clinically for the treatment of nodular basal cell carcinoma (BCC). METHODS: Enhancement of MAL-induced PpIX accumulation by the iron chelator CP94 was quantified fluorometrically in human cultured cells (including three dermatological cell types). An open, dose-escalating, pilot study was then conducted in patients with nodular BCC, to determine the safety of this pharmacological modification. RESULTS: Large enhancements in PpIX accumulation were observed in the cultured cells when co-incubated with the iron chelator CP94. Clinically the addition of CP94 was found to be feasible and safe. In addition greater reductions in tumor depth were observed in the CP94 co-incubated tumors. CONCLUSION: Iron chelation by CP94 is an effective enhancer of MAL-induced PpIX accumulation in vitro. This method of enhancement was safely applied to a clinical PDT protocol with no unexpected adverse effects reported. Although the clinical investigation was only intended to be a small pilot to assess safety, enhancements in tumor clearance were observed both clinically and histologically when CP94 was included in the photosensitizing cream.Duchy Health Charity Limite

Improving in vitro photodynamic therapy through the development of a novel iron chelating aminolaevulinic acid prodrug

This is the final version. Available on open access from Elsevier via the DOI in this recordBackground: Photodynamic therapy (PDT) is a light activated drug therapy that can be used to treat a number of cancers and precancers. It is particularly useful in its topical form in dermatology but improvement of efficacy is required to widen its application. Methods: An ester between aminolaevulinic acid (ALA) and CP94 was synthesised (AP2-18) and experimentally evaluated to determine whether protoporphyrin IX (PpIX)-induced PDT effectiveness could be improved. A biological evaluation of AP2-18 was conducted in cultured human primary cells with both PpIX fluorescence and cell viability (as determined via the neutral red assay) being assessed in comparison to the PpIX prodrugs normally utilised in clinical practice (aminolaevulinic acid (ALA) or its methyl ester (MAL)) either administered alone or with the comparator iron chelator, CP94. Results: No significant dark toxicity was observed in human lung fibroblasts but AP2-18 significantly increased PpIX accumulation above and beyond that achieved with ALA or MAL administration +/- CP94 in both human dermal fibroblasts and epithelial squamous carcinoma cells. On light exposure, the combined hydroxypyridinone iron chelating ALA prodrug AP2-18 generated significantly greater cytotoxicity than any of the other treatment parameters investigated when the lowest concentration (250 μM) was employed. Conclusions: Newly synthesised AP2-18 is therefore concluded to be an efficacious prodrug for PpIX-induced PDT in these dermatologically relevant human cells, achieving enhanced effects at lower concentrations than currently possible with existing pharmaceuticals.Medical Research Council (MRC)Killing Cancer (UK

The relationship between protoporphyrin IX photobleaching during real-time dermatological methyl-aminolevulinate photodynamic therapy (MAL-PDT) and subsequent clinical outcome.

Journal Article"This is the peer reviewed version of the following article: Lasers in Surgery and Medicine 42:613–619 (2010), which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/lsm.20943/pdf. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."BACKGROUND AND OBJECTIVE: The relationship between protoporphyrin IX (PpIX) photobleaching and cellular damage during aminolevulinic (ALA) photodynamic therapy (PDT) has been studied at the cellular level. This study assessed the capability of a non-invasive fluorescence imaging system (Dyaderm, Biocam, Germany), to monitor changes in PpIX during real time methyl-aminolevulinate (MAL) PDT in dermatological lesions, and thus to act as a predictive tool in terms of observed clinical outcome post-treatment. MATERIALS AND METHODS: Patients attending Royal Cornwall Hospital (Truro, UK) for MAL-PDT to licensed lesions (actinic keratosis, Bowen's disease, and basal cell carcinoma) were monitored using the pre-validated non-invasive fluorescence imaging system. Patients were imaged at three distinct time points: prior to the application of MAL, after the 3 hours of MAL application and immediately following light irradiation. The fluorescence intensity of the images were analysed with image analysis software and the percentage change in fluorescence during light irradiation was related to the clinical outcome observed 3 months following treatment. In total 100 patients underwent at least one session of MAL-PDT. RESULTS: Significantly higher levels of change in PpIX fluorescence during light irradiation (P0.500) was observed in the total levels of PpIX recorded after MAL application in patients undergoing partial and complete clearance at 3 months. CONCLUSIONS: PpIX photobleaching is indicative of the level of cellular damage PDT treatment will induce and therefore the clinical outcome expected within patients. This study indicated the potential of the commercially available fluorescence imaging system investigated to predict treatment success at the time of light irradiation and in the future it may be possible to employ it to individualise treatment parameters to improve dermatological PDT efficacy/outcome

Monitoring the accumulation and dissipation of the photosensitizer protoporphyrin IX during standard dermatological methyl-aminolevulinate photodynamic therapy utilizing non-invasive fluorescence imaging and quantification

Author's post-print is subject to a Creative Commons Attribution Non-Commercial No Derivatives LicenseBACKGROUND: Dermatological methyl-aminolevulinate photodynamic therapy (MAL-PDT) is utilized to successfully treat dermatological conditions. This study monitored fluorescence changes attributed to the accumulation and destruction of the photosensitizer, protoporphyrin IX (PpIX), at several different stages during the first and second treatments of clinical dermatological MAL-PDT. METHODS: A commercially available, non-invasive, fluorescence imaging system (Dyaderm, Biocam, Germany) was utilized to monitor fluorescence changes during the first and second MAL-PDT treatments in seventy-five lesions. RESULTS: The clinical data indicated statistically significant increases in fluorescence within lesions following the application of MAL for both treatments (P<0.001 and P<0.01 respectively) and subsequent statistically significant decreases in fluorescence within the lesions following light irradiation for both treatments (P<0.001 and P<0.01 respectively) whilst normal skin fluorescence remained unaltered. Lesions receiving a second treatment accumulated and dissipated significantly less PpIX (P<0.05) than during the first treatment. No significant differences were noted in PpIX accumulation or dissipation during MAL-PDT when gender, age, lesion type and lesion surface area were considered. CONCLUSIONS: It can therefore be concluded that PpIX fluorescence imaging can be used in real-time to assess PpIX levels during dermatological PDT. Similar observations were recorded from the three currently licensed indications indicating that the standard 'one size fits all' protocol currently employed appears to allow adequate PpIX accumulation, which is subsequently fully utilized during light irradiation regardless of patient age, gender or lesion surface area

How phenotypic matching based on neutral mating cues enables speciation in locally adapted populations

Maynard Smith's (American Naturalist, 1966, 100, 637) suggestion that in some cases a prerequisite for speciation is the existence of local ecological adaptations has not received much attention to date. Here, we test the hypothesis using a model like that of Maynard Smith but differing in the way animals disperse between niches. In previous studies, males disperse randomly between niches but females stay put in their natal niche. As a first step toward generalizing the model, we here analyze the case that equal proportions of the two sexes disperse between niches before breeding. Supporting Maynard Smith's (1966) hypothesis, we find that once local adaptations are established, a neutral mating cue at an independent locus can rapidly enable speciation in populations with a suitable mechanism for phenotype matching. We find that stable ecological polymorphisms are relatively insensitive to the strength of selection, but depend crucially on the extent of dispersal between niches, with a threshold of ~5% if population sizes in two niches are equal. At higher levels of dispersal, ecological differentiation is lost. These results contrast with those of earlier studies and shed light on why parapatric speciation is limited by the extent of gene flow. Our testable model provides a candidate explanation for the rapid speciation rates, diversity of appearance and occurrence of “species flocks” observed among some African cichlids and neotropical birds and may also have implications for the occurrence of punctuational change on phylogenies