The Place of Crossbred Lambs in Australian Lamb Production

The Australian sheep industry, particularly the lamb meat sector has undergone a major change in focus, such that consumer requirements are a paramount determinant for production and processing developments. This change has been facilitated by the use of cross breeding production systems where the benefits of heterosis are captured and the implementation of a performance recording system amongst initially, breeders of terminal sires. This sector of the industry has strongly embraced genetic selection using objectively measured traits and this is one of the contributors to the superior growth rate of crossbred progeny over pure bred progeny. A crossbreeding system does present challenges as it can also lead to fatter carcases depending on slaughter weight targets and thus less lean or saleable meat. This means that appropriate sire selection is mandatory. Which ever region of the world is under consideration; crossbreeding for meat production will return benefits and these will be further strengthened if the processing sector also adopts technology to enhance eating quality such as electrical stimulation and ageing

Drug screening to identify compounds to act as co-therapies for the treatment of Burkholderia species

Burkholderia pseudomallei is a soil-dwelling organism present throughout the tropics. It is the causative agent of melioidosis, a disease that is believed to kill 89,000 people per year. It is naturally resistant to many antibiotics, requiring at least two weeks of intravenous treatment with ceftazidime, imipenem or meropenem followed by 6 months of orally delivered co-trimoxazole. This places a large treatment burden on the predominantly middle-income nations where the majority of disease occurs. We have established a high-throughput assay for compounds that could be used as a co-therapy to potentiate the effect of ceftazidime, using the related non-pathogenic bacterium Burkholderia thailandensis as a surrogate. Optimization of the assay gave a Z' factor of 0.68. We screened a library of 61,250 compounds and identified 29 compounds with a pIC50 (-log10(IC50)) greater than five. Detailed investigation allowed us to down select to six "best in class" compounds, which included the licensed drug chloroxine. Co-treatment of B. thailandensis with ceftazidime and chloroxine reduced culturable cell numbers by two orders of magnitude over 48 hours, compared to treatment with ceftazidime alone. Hit expansion around chloroxine was performed using commercially available compounds. Minor modifications to the structure abolished activity, suggesting that chloroxine likely acts against a specific target. Finally, an initial study demonstrates the utility of chloroxine to act as a co-therapy to potentiate the effect of ceftazidime against B. pseudomallei. This approach successfully identified potential co-therapies for a recalcitrant Gram-negative bacterial species. Our assay could be used more widely to aid in chemotherapy to treat infections caused by these bacteria

Implementing telephone triage in general practice: a process evaluation of a cluster randomised controlled trial

Background: Telephone triage represents one strategy to manage demand for face-to-face GP appointments in primary care. However, limited evidence exists of the challenges GP practices face in implementing telephone triage. We conducted a qualitative process evaluation alongside a UK-based cluster randomised trial (ESTEEM) which compared the impact of GP-led and nurse-led telephone triage with usual care on primary care workload, cost, patient experience, and safety for patients requesting a same-day GP consultation. The aim of the process study was to provide insights into the observed effects of the ESTEEM trial from the perspectives of staff and patients, and to specify the circumstances under which triage is likely to be successfully implemented. Here we report perspectives of staff. Methods: The intervention comprised implementation of either GP-led or nurse-led telephone triage for a period of 2-3 months. A qualitative evaluation was conducted using staff interviews recruited from eight general practices (4 GP triage, 4 Nurse triage) in the UK, implementing triage as part of the ESTEEM trial. Qualitative interviews were undertaken with 44 staff members in GP triage and nurse triage practices (16 GPs, 8 nurses, 7 practice managers, 13 administrative staff). Results: Staff reported diverse experiences and perceptions regarding the implementation of telephone triage, its effects on workload, and on the benefits of triage. Such diversity were explained by the different ways triage was organised, the staffing models used to support triage, how the introduction of triage was communicated across practice staff, and by how staff roles were reconfigured as a result of implementing triage. Conclusion: The findings from the process evaluation offer insight into the range of ways GP practices participating in ESTEEM implemented telephone triage, and the circumstances under which telephone triage can be successfully implemented beyond the context of a clinical trial. Staff experiences and perceptions of telephone triage are shaped by the way practices communicate with staff, prepare for and sustain the changes required to implement triage effectively, as well as by existing practice culture, and staff and patient behaviour arising in response to the changes made. Trial registration: Current Controlled Trials ISRCTN20687662. Registered 28 May 2009

Development and Initial Findings of an Implementation Process Measure for Child Welfare System Change

This article describes a new measure designed to examine the process of implementation of child welfare systems change. The measure was developed to document the status of the interventions and strategies that are being implemented and the drivers that are being installed to achieve sustainable changes in systems. The measure was used in a Children’s Bureau-supported national effort to assess the ongoing implementation of 24 systems-change projects in child welfare jurisdictions across the country. The article describes the process for measure development, method of administration and data collection, and quantitative and qualitative findings

Electrochemical Quantification of D-Glucose during the Production of Bioethanol from Thermo-Mechanically Pre-treated Wheat Straw

Mechanical pre-treatment (disc refining) of wheat straw, at both atmospheric and elevated pressure, is shown to be an efficient process to access fermentable monosaccharides, with the potential to integrate within the infrastructure of existing first-generation bioethanol plants. The mild, enzymatic degradation of this sustainable lignocellulosic biomass affords ca. 0.10-0.13 g/g (dry weight) of D-glucose quantifiable voltammetrically in real time, over a two hundred-fold range in experimental laboratory scales (25 mL to 5.0 L), with pressure disc refining of the wheat straw enabling almost twice the amount of D-glucose to be generated during the hydrolysis stage than experiments using atmospheric refining (0.06 – 0.09 g/g dry weight). Fermentation of the resulting hydrolysate affords 0.08 – 0.10 g/g (dry weight) of ethanol over similar scales, with ethanol productivity at ca. 37 mg/(L h). These results demonstrate that minimal cellulose decomposition occurs during pressure refining of wheat straw, in contrast to hemicellulose, and suggest that the development of green, mechanochemical processes for the scalable and cost-effective manufacture of second-generation bioethanol requires improved cellulose decomposition

Anti-tumour efficacy of capecitabine in a genetically engineered mouse model of pancreatic cancer.

Capecitabine (CAP) is a 5-FU pro-drug approved for the treatment of several cancers and it is used in combination with gemcitabine (GEM) in the treatment of patients with pancreatic adenocarcinoma (PDAC). However, limited pre-clinical data of the effects of CAP in PDAC are available to support the use of the GEMCAP combination in clinic. Therefore, we investigated the pharmacokinetics and the efficacy of CAP as a single agent first and then in combination with GEM to assess the utility of the GEMCAP therapy in clinic. Using a model of spontaneous PDAC occurring in Kras(G12D); p53(R172H); Pdx1-Cre (KPC) mice and subcutaneous allografts of a KPC PDAC-derived cell line (K8484), we showed that CAP achieved tumour concentrations (∼25 µM) of 5-FU in both models, as a single agent, and induced survival similar to GEM in KPC mice, suggesting similar efficacy. In vitro studies performed in K8484 cells as well as in human pancreatic cell lines showed an additive effect of the GEMCAP combination however, it increased toxicity in vivo and no benefit of a tolerable GEMCAP combination was identified in the allograft model when compared to GEM alone. Our work provides pre-clinical evidence of 5-FU delivery to tumours and anti-tumour efficacy following oral CAP administration that was similar to effects of GEM. Nevertheless, the GEMCAP combination does not improve the therapeutic index compared to GEM alone. These data suggest that CAP could be considered as an alternative to GEM in future, rationally designed, combination treatment strategies for advanced pancreatic cancer

The FIRST Bright Quasar Survey. II. 60 Nights and 1200 Spectra Later

We have used the VLA FIRST survey and the APM catalog of the POSS-I plates as the basis for constructing a new radio-selected sample of optically bright quasars. This is the first radio-selected sample that is competitive in size with current optically selected quasar surveys. Using only two basic criteria, radio-optical positional coincidence and optical morphology, quasars and BL Lacs can be identified with 60% selection efficiency; the efficiency increases to 70% for objects fainter than magnitude 17. We show that a more sophisticated selection scheme can predict with better than 85% reliability which candidates will turn out to be quasars. This paper presents the second installment of the FIRST Bright Quasar Survey with a catalog of 636 quasars distributed over 2682 square degrees. The quasar sample is characterized and all spectra are displayed. The FBQS detects both radio-loud and radio-quiet quasars out to a redshift z>3. We find a large population of objects of intermediate radio-loudness; there is no evidence in our sample for a bimodal distribution of radio characteristics. The sample includes ~29 broad absorption line quasars, both high and low ionization, and a number of new objects with remarkable optical spectra.Comment: 41 pages plus 39 gifs which contain all quasar spectra. Accepted for publication in the Astrophysical Journal Supplement Serie

SPARC independent drug delivery and antitumour effects of nab-paclitaxel in genetically engineered mice.

DESIGN: Pharmacokinetic and pharmacodynamic parameters of cremophor-paclitaxel, nab-paclitaxel (human-albumin-bound paclitaxel, Abraxane) and a novel mouse-albumin-bound paclitaxel (m-nab-paclitaxel) were evaluated in genetically engineered mouse models (GEMMs) by liquid chromatography-tandem mass spectrometry (LC-MS/MS), histological and biochemical analysis. Preclinical evaluation of m-nab-paclitaxel included assessment by three-dimensional high-resolution ultrasound and molecular analysis in a novel secreted protein acidic and rich in cysteine (SPARC)-deficient GEMM of pancreatic ductal adenocarcinoma (PDA). RESULTS: nab-Paclitaxel exerted its antitumoural effects in a dose-dependent manner and was associated with less toxicity compared with cremophor-paclitaxel. SPARC nullizygosity in a GEMM of PDA, Kras(G12D);p53(flox/-);p48Cre (KPfC), resulted in desmoplastic ductal pancreas tumours with impaired collagen maturation. Paclitaxel concentrations were significantly decreased in SPARC null plasma samples and tissues when administered as low-dose m-nab-paclitaxel. At the maximally tolerated dose, SPARC deficiency did not affect the intratumoural paclitaxel concentration, stromal deposition and the immediate therapeutic response. CONCLUSIONS: nab-Paclitaxel accumulates and acts in a dose-dependent manner. The interaction of plasma SPARC and albumin-bound drugs is observed at low doses of nab-paclitaxel but is saturated at therapeutic doses in murine tumours. Thus, this study provides important information for future preclinical and clinical trials in PDA using nab-paclitaxel in combination with novel experimental and targeted agents

X-ray properties of radio-selected star forming galaxies in the Chandra-COSMOS survey

X-ray surveys contain sizable numbers of star forming galaxies, beyond the AGN which usually make the majority of detections. Many methods to separate the two populations are used in the literature, based on X-ray and multiwavelength properties. We aim at a detailed test of the classification schemes and to study the X-ray properties of the resulting samples. We build on a sample of galaxies selected at 1.4 GHz in the VLA-COSMOS survey, classified by Smolcic et al. (2008) according to their optical colours and observed with Chandra. A similarly selected control sample of AGN is also used for comparison. We review some X-ray based classification criteria and check how they affect the sample composition. The efficiency of the classification scheme devised by Smolcic et al. (2008) is such that ~30% of composite/misclassified objects are expected because of the higher X-ray brightness of AGN with respect to galaxies. The latter fraction is actually 50% in the X-ray detected sources, while it is expected to be much lower among X-ray undetected sources. Indeed, the analysis of the stacked spectrum of undetected sources shows, consistently, strongly different properties between the AGN and galaxy samples. X-ray based selection criteria are then used to refine both samples. The radio/X-ray luminosity correlation for star forming galaxies is found to hold with the same X-ray/radio ratio valid for nearby galaxies. Some evolution of the ratio may be possible for sources at high redshift or high luminosity, tough it is likely explained by a bias arising from the radio selection. Finally, we discuss the X-ray number counts of star forming galaxies from the VLA- and C-COSMOS surveys according to different selection criteria, and compare them to the similar determination from the Chandra Deep Fields. The classification scheme proposed here may find application in future works and surveys.Comment: 15 pages, 7 figures, 3 table