Time for change: a study of enrolment decision dynamics for admission into English secondary education

Cross-sectional studies suggest a prevalence of mental health problems from the age that children change to English secondary schools but there are few longitudinal appraisals of these issues and how enrolment policies influence psychological wellbeing. This research focuses on key factors linking competition for secondary schools and family responses to such challenges to determine enrolment policies that can sustain wellbeing longer-term. Integrated, model-based multimethodology was used in this urban, case-based study. Views were induced from multi-agency, expert practitioners to agree a system dynamics concept model. Parental decision-making behaviours were deduced by survey to understand key factors for model calibration. Dynamic system sensitivities were abduced from the simulation model before comparing long-term psychosocial impacts on children from expert, policy-support suggestions. Modelling demonstrates that two principal feedback loops influence family psychosocial systems when deciding secondary schools (parent-child wellbeing reinforcement plus knowledge of schools balancing parent concerns). Exogenous competition stressors on psychosocial systems can erode parent knowledge while testing student resolve. Competition guidance to remove risk-laden school options (league table comparison) before sequencing any remaining choices by profit (school visits), are not always used deciding urban secondary schools. Instead, families lacking experience can adopt decisive styles based on parent needs alone. Given autocratic leadership, child wellbeing rapidly deteriorates when student needs cannot be met by schools. Rather than ending student-selective entrance tests or raising knowledge of schools at visits, effective multi-agency support policy helps by increasing school choice debate frequency within families to address psychosocial system imbalances. The research makes a clear, three-way contribution to knowledge. Firstly, intrinsic case study theory is enhanced by data triangulation between induced, deduced and abduced research approaches. Secondly, the system dynamics discipline is strengthened by studying compulsory school enrolment. Finally, developing practice-based policy through multi-agency groups endorses cooperative rather than unilateral solutions, for helping change lives

TAK1 Is Required for Dermal Wound Healing and Homeostasis

Dermal connective tissue is a supportive structure required for skin’s barrier function; dysregulated dermal homeostasis results in chronic wounds and fibrotic diseases. The multifunctional cytokine transforming growth factor (TGF) β promotes connective tissue deposition, repair, and fibrosis. TGF-β acts through well-defined canonical pathways; however, the non-canonical pathways through which TGF-β selectively promotes connective tissue deposition are unclear. In dermal fibroblasts, we show that inhibition of the non-canonical TGF-β-activated kinase 1 (TAK1) selectively reduced the ability of TGF-β to induce expression of a cohort of wound healing genes, such as collagens, CCN2, TGF-β1, and IL-6. Fibroblast-specific TAK1-knockout mice showed impaired cutaneous tissue repair and decreased collagen deposition, α-smooth muscle actin and CCN2 expression, proliferating cell nuclear antigen staining, and c-Jun N-terminal kinase and p38, but not Smad3, phosphorylation. TAK1-deficient fibroblasts showed reduced cell proliferation, migration, cell attachment/spreading, and contraction of a floating collagen gel matrix. TAK1-deficient mice also showed progressively reduced skin thickness and collagen deposition. Thus, TAK1 is essential for connective tissue deposition in the dermis

Rural Cultural Studies: Introduction

This themed section of Australian Humanities Review seeks to establish the emerging field of \u27rural cultural studies\u27 firmly on the agenda of the contemporary humanities and social sciences. This is a timely intervention as rural Australia has featured increasingly over the last decade and especially over the last few years as a topic of national policy attention, public commentary and social analysis. If the notion of a crisis in rural Australia has become something of a one-sided cliché, the changes being faced in non-urban-rural, remote and regional-Australia are nonetheless significant, complex and widespread. For example, one of the topics for the federal 2020 Summit, \u27Rural Australia\u27, addressed future policy directions for rural industries and populations. In this wider context, the purpose of the present collection of papers is to argue for the significance of the cultural dimension-and the multiple dimensions of the cultural-in understanding the key issues of demographic change, economic productivity, environmental and climatic crisis, Indigenous/non-indigenous relations and land ownership, and the role of \u27cultural\u27 factors in the renewal, or potential renewal, of country towns and communities

Sourcing cells for gut tissue engineering: understanding and inducing embryonic stem cell differentiation to the intestinal cell lineage

Tissue engineering of any tissue type requires the combination of a supporting scaffold, a range of biological factors and a suitable source of cells. This source of cells must satisfy a number of criteria:- • The ability to form all of the mature/specialised cell types found in the target tissue. • Readily obtainable. • Readily maintainable in the laboratory without requiring excessive resources or time. For intestinal tissue engineering there are a number of issues associated with the use of tissue derived stem cells particularly quantity of normal tissue available (from the patient) and maintenance and expansion of the cells when cultured in vitro. Using embryonic stem cells offers a potential alternative strategy but methods must be established to efficiently differentiate the cells towards the desired fate. Many strategies for differentiating embryonic stem cells are based upon treatment with growth factors in vitro. There is a (logistical) limit to the degree of complexity that these systems can achieve and therefore a limit to the number of differentiation signals that occur during in vivo development that can be mimicked. In recent years using embryonic tissue to provide signals to undifferentiated cells has proved a successful method of directing the differentiation of naïve cells towards a particular fate (with the choice of tissue determined by the desired target cell type). The aims of this thesis were to explore the potential of differentiating embryonic stem cells towards the intestinal progenitor fate using a combination of in vitro cell culture treatment with the growth factor Activin-A and ex vivo co-culture with embryonic chick gut tissue. Previous studies [Kubo et al 2004, Tada et al 2005, Yasunaga et al 2005, D’Amour et al 2005, MacClean et al 2007] have shown that Activin-A treatment will induce embryonic cells to more efficiently differentiate to definitive endoderm, the germ layer from which the intestines (and other visceral organs) arise. These techniques were applied to the Columnar Epithelial Epiblast murine embryonic stem cell line and cell differentiation was then evaluated at the molecular level using Reverse Transcription-Polymerase Chain Reaction, immunocytochemistry and Western blotting. Activin-A treatment produced an upregulation of definitive endoderm markers at both the mRNA and proteomic levels compared to the control conditions. However the cell population produced retained expression of pluripotent markers and showed some expression of markers of other cell lineages. Further studies [Sugie et al 2005, Fair et al 2003, Van Vranken et al 2005, Coleman et al 2007, Krassowska et al 2006] have shown that co-culture of embryonic stem cells with early stage embryonic tissue can induce the formation of particular tissue types; the tissue must be selected based on proximity to the target cell type during development. This exposes the embryonic stem cells to the signals that prompt differentiation towards the target tissue during normal development. With gut tissue much signalling occurs between the different tissue layers that make up the whole organ both during development and in adult tissue. Ex vivo co-culture of murine embryonic stem cells with embryonic chick gut tissue was used to direct their differentiation to the intestinal epithelial stem cell fate. Before the co-culture was carried out various experiments were carried out to establish if the proposed protocol was viable e.g. defining how long chick gut tissue explants could survive in culture. Once this had been established co-culture experiments were undertaken and cell differentiation was then evaluated at the molecular level using Reverse Transcription-Polymerase Chain Reaction, immunocytochemistry and Western blotting. The cells showed some expression of intestinal epithelial stem cell markers at both the mRNA and proteomic levels following co-culture. The cells were also assessed at a physiological/functional level by evaluating their ability to form a functional intestinal epithelial barrier. This was achieved using an in vitro co-culture model with intestinal subepithelial myofibroblasts by measuring transepithelial resistance, permeability to protein and morphology in a simple tissue model co-culture. The cells did not display the morphological or physiological characteristics associated with intestinal epithelial cells in the model system. Overall this work has shown that co-culturing pluripotent mES cells with embryonic chick gut tissue can induce differentiation towards the ISC fate. Pre-treating the cells with growth factors in vitro did not seem to enhance this differentiation but there was scope to refine these techniques. Following the differentiation protocols the cells did not display the desired physiological characteristics but again there was scope to refine the techniques particularly with regard to selecting cells positive for the expression of the chosen molecular markers. These techniques show promise but do require some further development

Cost-effectiveness of adult circumcision in a resource-rich setting for HIV prevention among men who have sex with men

Background.&nbsp; We examined the effects and cost‐effectiveness of 4 strategies of circumcision in a resource‐rich setting (Australia) in a population of men who have sex with men (MSM).Method.&nbsp; We created a dynamic mathematical transmission model and performed an economic analysis to estimate the costs, outcomes, and cost‐effectiveness of different strategies, compared with those of the status quo. Strategies included circumcision of all MSM at age 18 years, circumcision of all MSM aged 35&ndash;44 years, circumcision of all insertive MSM aged 18 years, and circumcision of all MSM aged 18 years . All costs are reported in US dollars, with a cost‐effectiveness threshold of 42,000 per quality‐adjusted life‐year.Results.  We find that 2%–5% of human immunodeficiency virus (HIV) infections would be averted per year, with initial costs ranging from 3.6 million to $95.1 million, depending on the strategy. The number of circumcisions needed to prevent 1 HIV infection would range from 118 through 338. Circumcision of predominately insertive MSM would save$21.7 million over 25 years with a $62.2 million investment. Strategies to circumcise 100% of all MSM and to circumcise MSM aged 35&ndash;44 years would be cost‐effective; the latter would require a smaller investment. The least cost‐effective approach is circumcision of young MSM close to their sexual debut. Results are very sensitive to assumptions about the cost of circumcision, the efficacy of circumcision, sexual preferences, and behavioral disinhibition.Conclusions.&nbsp; Circumcision of adult MSM may be cost‐effective in this resource‐rich setting. However, the intervention costs are high relative to the costs spent on other HIV prevention programs.<br /

A northern powerhouse, or an unwelcome imposition? experts respond to George Osborne’s Greater Manchester Mayor proposals

The Chancellor recently announced that in order to help make his “Northern Powerhouse” idea reality that the Greater Manchester City Region would see itself gain an elected, “London-style” Mayor, despite residents of Manchester City Council narrowly rejecting proposals for an Directly Elected Mayor for their local authority in 2011. Democratic Audit asked experts to respond to the news, with mixed results

Utilising co-design to improve outpatient neurological care in a rural setting

It has been identified that the physiotherapy needs of patients with central neurological conditions are specific and that this cohort are generally under-serviced in rural and remote areas in Australia. A quality improvement project was undertaken to improve patient experience in outpatient physiotherapy services in Tasmania, facilitating increased self-efficacy and quality of life, in patients with central chronic neurological conditions.. An experience-based co-design approach was utilised, involving past and current patients as well as physiotherapy staff in the project design, data collection, analysis and evaluation phases. The results suggest that timely access to care and goal achievement are common areas of need across both patient and staff cohorts. Patients also identified that shared-decision making is important for improving patient experience and staff were generally unclear on what services were available. The findings from this study demonstrate the importance of including patients and staff in the health service improvement process. Experience Framework This article is associated with the Innovation & Technology lens of The Beryl Institute Experience Framework. (http://bit.ly/ExperienceFramework) Access other PXJ articles related to this lens. Access other resources related to this len

Independent evolution of neurotoxin and flagellar genetic loci in proteolytic Clostridium botulinum

<p>Abstract</p> <p>Background</p> <p>Proteolytic <it>Clostridium botulinum </it>is the causative agent of botulism, a severe neuroparalytic illness. Given the severity of botulism, surprisingly little is known of the population structure, biology, phylogeny or evolution of <it>C. botulinum</it>. The recent determination of the genome sequence of <it>C. botulinum </it>has allowed comparative genomic indexing using a DNA microarray.</p> <p>Results</p> <p>Whole genome microarray analysis revealed that 63% of the coding sequences (CDSs) present in reference strain ATCC 3502 were common to all 61 widely-representative strains of proteolytic <it>C. botulinum </it>and the closely related <it>C. sporogenes </it>tested. This indicates a relatively stable genome. There was, however, evidence for recombination and genetic exchange, in particular within the neurotoxin gene and cluster (including transfer of neurotoxin genes to <it>C. sporogenes</it>), and the flagellar glycosylation island (FGI). These two loci appear to have evolved independently from each other, and from the remainder of the genetic complement. A number of strains were atypical; for example, while 10 out of 14 strains that formed type A1 toxin gave almost identical profiles in whole genome, neurotoxin cluster and FGI analyses, the other four strains showed divergent properties. Furthermore, a new neurotoxin sub-type (A5) has been discovered in strains from heroin-associated wound botulism cases. For the first time, differences in glycosylation profiles of the flagella could be linked to differences in the gene content of the FGI.</p> <p>Conclusion</p> <p>Proteolytic <it>C. botulinum </it>has a stable genome backbone containing specific regions of genetic heterogeneity. These include the neurotoxin gene cluster and the FGI, each having evolved independently of each other and the remainder of the genetic complement. Analysis of these genetic components provides a high degree of discrimination of strains of proteolytic <it>C. botulinum</it>, and is suitable for clinical and forensic investigations of botulism outbreaks.</p

Discovery of a meteoritic ejecta layer containing unmelted impactor fragments at the base of Paleocene lavas, Isle of Skye, Scotland

Evidence for meteorite impacts in the geological record may include the presence of shocked minerals, spherule layers, and geochemical anomalies. However, it is highly unusual to nd unmelted crystals from the actual impactor within an ejecta layer. Here we detail the rst recorded occurrence of vanadium-rich osbornite (TiVN) on Earth, from two sites on Skye, northwest Scotland, which are interpreted as part of a meteoritic ejecta layer. TiVN has only previously been reported as dust from comet Wild 2, but on Skye it has been identi ed as an unmelted phase. Both ejecta layer sites also contain niobium-rich osbornite (TiNbN), which has not previously been reported. An extraterrestrial origin for these deposits is strongly supported by the presence of reidite (a high-pressure zircon polymorph), which is only found naturally at sites of meteorite impact. Barringerite [(Fe,Ni)2P], baddeleyite (ZrO2), alabandite (MnS), and carbon-bearing native iron spherules, together with planar deformation features and diaplectic glass in quartz, further support this thesis. We demonstrate through eld relationships and Ar-Ar dating that the meteorite strike occurred during the mid-Paleocene. This is the rst recorded mid-Paleocene impact event in the region and is coincident with the onset of magmatism in the British Palaeogene Igneous Province (BPIP). The Skye ejecta layer deposits provoke important questions regarding their lateral extent at the base of the BPIP and the possibility of their presence elsewhere beneath the much larger North Atlantic Igneous Province