Review: "Context : A framework for its Influence on Evaluation Practice (New Directions for Evaluation No. 135)" edited by Rog, D. J.; Fitzpatrick, J. L. and Conner, R. F.

This book offers a framework for the influence of context on evaluation practice and is applied to three case studies: environmental context; indigenous context and political context; and finishes with a process for implementation.

Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis : protocol for a randomised controlled trial

Background Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. Methods A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW(135)) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and >= 6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged >= 6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine-related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged >= 6 years; and vaccine safety. Discussion As H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis.

Percutaneous coronary intervention with drug-eluting stents or coronary artery bypass surgery in subjects with type 2 diabetes : evaluation of: Farkouth ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med 2012;367(25):2375-84, and Contini GA, Nicolini F, Fortuna D, et al. Five-year outcomes of surgical or percutaneous myocardial revascularization in diabetic patients. Int J Cardiol 2012. [Epub ahead of print]

There is debate as to whether percutaneous coronary intervention (PCI) with drug-eluting stents or coronary artery bypass surgery (CABG) is the best procedure for subjects with type 2 diabetes and coronary artery disease requiring revascularization. There is some evidence that following these procedures there is less further revascularization with CABG than PCI in subjects with diabetes. Two recent studies; the FREEDOM (Future Revascularization Evaluation in patients with Diabetes mellitus: Optimal Management of Multivessel Disease) trial, and a trial using a real world diabetic population from a Registry, have shown that the benefits of CABG over PCI in subjects with type 2 diabetes extends to lower rates of death and myocardial infarct, in addition to lower rates of revascularization. However, the rates of stroke may be higher with CABG than PCI with drug-eluting stents in this population. Thus, if CABG is going to be preferred to PCI in subjects with type 2 diabetes and multivessel coronary disease, consideration should be given to how to reduce the rates of stroke with CABG.

Bilingualism, literacy and NAPLAN : ongoing challenges for EAL/D education [Editorial]

Advocacy is integral to the work of many TESOL specialists. For several decades, ACTA and the state TESOL associations, along with other professional associations, and individual teachers, researchers and administrators have all engaged with conversations about EAL/D education in public forums. These advocates have drawn attention to implications of policy developments for EAL/D students; they have proffered alternative forms of curriculum, pedagogy and assessment to better account for the particularity of EAL/D learning pathways; they have argued the necessity of specialist EAL/D teaching. In response to the Australian Language and Literacy Policy of the early 1990s, for example, there was “a frenzy of writing responses… a conference… and attempts to publicise what was going on through the press and television” (Moore, 1995, p. 6). It is in this spirit that this double issue of TESOL in Context has been compiled...

The contributions of solar ultraviolet radiation exposure and other determinants to Serum 25-Hydroxyvitamin D concentrations in Australian adults : the AusD study

The Quantitative Assessment of Solar UV [ultraviolet] Exposure for Vitamin D Synthesis in Australian Adults (AusD) Study aimed to better define the relationship between sun exposure and serum 25-hydroxyvitamin D (25(OH)D) concentration. Cross-sectional data were collected between May 2009 and December 2010 from 1,002 participants aged 18-75 years in 4 Australian sites spanning 24° of latitude. Participants completed the following: 1) questionnaires on sun exposure, dietary vitamin D intake, and vitamin D supplementation; 2) 10 days of personal ultraviolet radiation dosimetry; 3) a sun exposure and physical activity diary; and 4) clinical measurements and blood collection for 25(OH)D determination. Our multiple regression model described 40% of the variance in 25(OH)D concentration; modifiable behavioral factors contributed 52% of the explained variance, and environmental and demographic or constitutional variables contributed 38% and 10%, respectively. The amount of skin exposed was the single strongest contributor to the explained variance (27%), followed by location (20%), season (17%), personal ultraviolet radiation exposure (8%), vitamin D supplementation (7%), body mass index (weight (kg)/height (m)2) (4%), and physical activity (4%). Modifiable behavioral factors strongly influence serum 25(OH)D concentrations in Australian adults. In addition, latitude was a strong determinant of the relative contribution of different behavioral factors.

A concise approach to the polycyclic scaffold of frondosin D

Frondosins A−E, 1−5 (Figure 1), are a family of related marine sesquiterpenoids first isolated in their dextro-rotatory form from the sponge Dysidea frondosa.(1a) Additionally, levo-rotatory frondosins A and D were isolated from an unidentified Eurospongia species.(1b) Frondosins A−E are compounds of interest due to their promising interleukin-8 (IL-8) affinity and protein kinase C inhibition.(1a) IL-8 antagonists are of particular interest in view of their antiinflammatory,(2a) anti-HIV,(1b, 2b) and antitumor(2c-2f) properties. To date, frondosins A, B, and C have been synthesized.(3) Notwithstanding these successes, the frondosins have proved quite a formidable synthetic challenge, and as of yet, there has been no synthesis of frondosin D or E. In this report, we describe our approaches to the molecular scaffold of frondosins D. This work has culminated in a very effective means of producing the trimethylbicyclo[5.4.0]undecane ring system common to all frondosins (shown in bold, Figure 1).

A detailed investigation of nominally 2-D radical-farming scramjet combustion

This paper reports on an investigation of the flow/chemistry coupling inside a nominally two-dimensional inlet-fuelled scramjet configuration. The experiments were conducted at a freestream Mach number of 7.3 and a total flow enthalpy of 4.3MJ/kg corresponding to a Mach 9.7 flight condition. The phenomenon of radical-farming has been studied in detail using two-dimensional OH* chemiluminescence imaging and emission spectroscopy. High signal levels of excited OH (OH*) were detected behind the first shock reflections inside the combustion chamber upstream of any measurable pressure rise from combustion, which occurred towards the rear of the combustor. The production of OH in the first hot pocket initiates the ignition process and then accelerates the combustion process in the next downstream hot pocket. This was confirmed by numerical simulations of premixed hydrogen/air flow through the scramjet. Chemical kinetics analyses reveal that the ignition process is governed by the interaction between various reaction groups leading to a chainbranching explosion for low mean temperature and pressure combustion flowfields.

High-level expression of Rhodotorula gracilis d-amino acid oxidase in Pichia pastoris

By combining gene design and heterologous over-expression of Rhodotorula gracilis D-amino acid oxidase (RgDAO) in Pichia pastoris, enzyme production was enhanced by one order of magnitude compared to literature benchmarks, giving 350 kUnits/l of fed-batch bioreactor culture with a productivity of 3.1 kUnits/l h. P. pastoris cells permeabilized by freeze-drying and incubation in 2-propanol (10% v/v) produce a highly active (1.6 kUnits/g dry matter) and stable oxidase preparation. Critical bottlenecks in the development of an RgDAO catalyst for industrial applications have been eliminated.

Stepwise engineering of a Pichia pastoris D-amino acid oxidase whole cell catalyst

Trigonopsis variabilis D-amino acid oxidase (TvDAO) is a well characterized enzyme used for cephalosporin C conversion on industrial scale. However, the demands on the enzyme with respect to activity, operational stability and costs also vary with the field of application. Processes that use the soluble enzyme suffer from fast inactivation of TvDAO while immobilized oxidase preparations raise issues related to expensive carriers and catalyst efficiency. Therefore, oxidase preparations that are more robust and active than those currently available would enable a much broader range of economically viable applications of this enzyme in fine chemical syntheses. A multi-step engineering approach was chosen here to develop a robust and highly active Pichia pastoris TvDAO whole-cell biocatalyst. As compared to the native T. variabilis host, a more than seven-fold enhancement of the intracellular level of oxidase activity was achieved in P. pastoris through expression optimization by codon redesign as well as efficient subcellular targeting of the enzyme to peroxisomes. Multi copy integration further doubled expression and the specific activity of the whole cell catalyst. From a multicopy production strain, about 1.3 x 103 U/g wet cell weight (wcw) were derived by standard induction conditions feeding pure methanol. A fed-batch cultivation protocol using a mixture of methanol and glycerol in the induction phase attenuated the apparent toxicity of the recombinant oxidase to yield final biomass concentrations in the bioreactor of >or= 200 g/L compared to only 117 g/L using the standard methanol feed. Permeabilization of P. pastoris using 10% isopropanol yielded a whole-cell enzyme preparation that showed 49% of the total available intracellular oxidase activity and was notably stabilized (by three times compared to a widely used TvDAO expressing Escherichia coli strain) under conditions of D-methionine conversion using vigorous aeration. Stepwise optimization using a multi-level engineering approach has delivered a new P. pastoris whole cell TvDAO biocatalyst showing substantially enhanced specific activity and stability under operational conditions as compared to previously reported preparations of the enzyme. The production of the oxidase through fed-batch bioreactor culture and subsequent cell permeabilization is high-yielding and efficient. Therefore this P. pastoris catalyst has been evaluated for industrial purposes.

The role of vascularization in 3-D tissue engineering

The role of vascularization in 3-D tissue engineering was studied. Mouse fat, angiogenic growth factors, adult human stem cells and fat tissue have been inserted and subsequent tissue growth was monitored. Human fat grafts or human lipoaspirates in SCID mouse chambers induced mouse fat generation at 6 weeks. Tissue engineering models utilizing intrinsic vascularization have major advantages including rapid and appropriate vascularization of new tissues.

Emerging stem cell controls : nanomaterials and plasma effects

Stem cells (SC) are among the most promising cell sources for tissue engineering due to their ability to self-renew and differentiate, properties that underpin their clinical application in tissue regeneration. As such, control of SC fate is one of the most crucial issues that needs to be fully understood to realise their tremendous potential in regenerative biology. The use of functionalized nanostructured materials (NM) to control the microscale regulation of SC has offered a number of new features and opportunities for regulating SC. However, fabricating and modifying such NM to induce specific SC response still represent a significant scientific and technological challenge. Due to their versatility, plasmas are particularly attractive for the manufacturing and modification of tailored nanostructured surfaces for stem cell control. In this review, we briefly describe the biological role of SC and the mechanisms by which they are controlled and then highlight the benefits of using a range of nanomaterials to control the fate of SC. We then discuss how plasma nanoscience research can help produce/functionalise these NMs for more effective and specific interaction with SCs. The review concludes with a perspective on the advantages and challenges of research at the intersection between plasma physics, materials science, nanoscience, and SC biology.

Serum 25-hydroxy vitamin D concentrations are more deficient/insufficient in peritoneal dialysis than haemodialysis patients in a sunny climate

Background Research has identified associations between serum 25(OH)D and a range of clinical outcomes in chronic kidney disease and wider populations. The present study aimed to investigate vitamin D deficiency/insufficiency in dialysis patients and the relationship with vitamin D intake and sun exposure. Methods A cross-sectional study was used. Participants included 30 peritoneal dialysis (PD) (43.3% male; 56.87 ± 16.16 years) and 26 haemodialysis (HD) (80.8% male; 63.58 ± 15.09 years) patients attending a department of renal medicine. Explanatory variables were usual vitamin D intake from diet/supplements (IU day−1) and sun exposure (min day−1). Vitamin D intake, sun exposure and ethnic background were assessed by questionnaire. Weight, malnutrition status and routine biochemistry were also assessed. Data were collected during usual department visits. The main outcome measure was serum 25(OH)D (nm). Results Prevalence of inadequate/insufficient vitamin D intake differed between dialysis modality, with 31% and 43% found to be insufficient (<50 nm) and 4% and 33% found to be deficient (<25 nm) in HD and PD patients, respectively (P < 0.001). In HD patients, there was a correlation between diet and supplemental vitamin D intake and 25(OH)D (ρ = 0.84, P < 0.001) and average sun exposure and 25(OH)D (ρ = 0.50, P < 0.02). There were no associations in PD patients. The results remained significant for vitamin D intake after multiple regression, adjusting for age, gender and sun exposure. Conclusions The results highlight a strong association between vitamin D intake and 25(OH)D in HD but not PD patients, with implications for replacement recommendations. The findings indicate that, even in a sunny climate, many dialysis patients are vitamin D deficient, highlighting the need for exploration of determinants and consequences.