Comparison of decision tree, support vector machines, and Bayesian network approaches for classification of falls in Parkinson’s disease

Being able to accurately predict the risk of falling is crucial in patients with Parkinson’s dis- ease (PD). This is due to the unfavorable effect of falls, which can lower the quality of life as well as directly impact on survival. Three methods considered for predicting falls are decision trees (DT), Bayesian networks (BN), and support vector machines (SVM). Data on a 1-year prospective study conducted at IHBI, Australia, for 51 people with PD are used. Data processing are conducted using rpart and e1071 packages in R for DT and SVM, con- secutively; and Bayes Server 5.5 for the BN. The results show that BN and SVM produce consistently higher accuracy over the 12 months evaluation time points (average sensitivity and specificity > 92%) than DT (average sensitivity 88%, average specificity 72%). DT is prone to imbalanced data so needs to adjust for the misclassification cost. However, DT provides a straightforward, interpretable result and thus is appealing for helping to identify important items related to falls and to generate fallers’ profiles.

The mechanisms of human renal epithelial cell modulation of autologous dendritic cell phenotype and function

Proximal tubule epithelial cells (PTEC) of the kidney line the proximal tubule downstream of the glomerulus and play a major role in the re-absorption of small molecular weight proteins that may pass through the glomerular filtration process. In the perturbed disease state PTEC also contribute to the inflammatory disease process via both positive and negative mechanisms via the production of inflammatory cytokines which chemo-attract leukocytes and the subsequent down-modulation of these cells to prevent uncontrolled inflammatory responses. It is well established that dendritic cells are responsible for the initiation and direction of adaptive immune responses. Both resident and infiltrating dendritic cells are localised within the tubulointerstitium of the renal cortex, in close apposition to PTEC, in inflammatory disease states. We previously demonstrated that inflammatory PTEC are able to modulate autologous human dendritic cell phenotype and functional responses. Here we extend these findings to characterise the mechanisms of this PTEC immune-modulation using primary human PTEC and autologous monocyte-derived dendritic cells (MoDC) as the model system. We demonstrate that PTEC express three inhibitory molecules: (i) cell surface PD-L1 that induces MoDC expression of PD-L1; (ii) intracellular IDO that maintains the expression of MoDC CD14, drives the expression of CD80, PD-L1 and IL-10 by MoDC and inhibits T cell stimulatory capacity; and (iii) soluble HLA-G (sHLA-G) that inhibits HLA-DR and induces IL-10 expression by MoDC. Collectively the results demonstrate that primary human PTEC are able to modulate autologous DC phenotype and function via multiple complex pathways. Further dissection of these pathways is essential to target therapeutic strategies in the treatment of inflammatory kidney disorders.

Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases

Androgenetic alopecia (AGA) is a highly heritable condition and the most common form of hair loss in humans. Susceptibility loci have been described on the X chromosome and chromosome 20, but these loci explain a minority of its heritable variance. We conducted a large-scale meta-analysis of seven genome-wide association studies for early-onset AGA in 12,806 individuals of European ancestry. While replicating the two AGA loci on the X chromosome and chromosome 20, six novel susceptibility loci reached genome-wide significance (p = 2.62x10(-)(9)-1.01x10(-)(1)(2)). Unexpectedly, we identified a risk allele at 17q21.31 that was recently associated with Parkinson's disease (PD) at a genome-wide significant level. We then tested the association between early-onset AGA and the risk of PD in a cross-sectional analysis of 568 PD cases and 7,664 controls. Early-onset AGA cases had significantly increased odds of subsequent PD (OR = 1.28, 95% confidence interval: 1.06-1.55, p = 8.9x10(-)(3)). Further, the AGA susceptibility alleles at the 17q21.31 locus are on the H1 haplotype, which is under negative selection in Europeans and has been linked to decreased fertility. Combining the risk alleles of six novel and two established susceptibility loci, we created a genotype risk score and tested its association with AGA in an additional sample. Individuals in the highest risk quartile of a genotype score had an approximately six-fold increased risk of early-onset AGA [odds ratio (OR) = 5.78, p = 1.4x10(-)(8)(8)]. Our results highlight unexpected associations between early-onset AGA, Parkinson's disease, and decreased fertility, providing important insights into the pathophysiology of these conditions.

Lessons to be learnt from two professional development programs

The involvement of teachers in any process which seeks to enhance classroom pedagogy is vital. In this area, professional development (PD) for teachers can be effective in developing and broadening classroom practices, but the process takes time. Teachers need time to reflect on their practice and be confident in implementing new programs and strategies by taking risks and employing different approaches in their pedagogy. There are various ways of initiating professional development which also take into account time for reflection. One is by the use of professional development to improve knowledge and skills. Another way is by teachers observing the practice of their colleagues before reflecting and modifying their own practice. This study discusses the findings of a case study where two different PD programs in a single secondary school were implemented with the assistance of two University Lecturers. The study revealed that although there were positive reflections on the development of knowledge and skills from the PD, factors such as collegiality and time and infrastructure constraints impacted the teachers involved in both the Reflective Practice and the technology PD programs. The school was part of the Brisbane Catholic Education Office (BCE) in Queensland, Australia and the researchers were both Senior Lecturers at the Queensland University of Technology in Brisbane.

More equal than others?: Meeting the professional development needs of rural primary and secondary science teachers

It is often assumed that teachers in rural and remote schools are at a disadvantage when it comes to accessing professional development. But is there sufficient evidence to support this assumption? This paper reports findings from two national surveys comparing the professional development priorities of primary and secondary science teachers from metropolitan, provincial and remote schools. The research found that while teachers' unmet needs for some PD opportunities increased significantly with school remoteness, this was not the case for all opportunities. In teasing out the different PD priorities of primary and secondary science teachers, the paper provides evidence to help education authorities and professional organisations address the specific needs of teachers in different locations.

Digital revolution or digital divide: Will rural teachers get a piece of the professional development pie?

In order to sustain the rural education community, access to high quality professional development opportunities must become a priority. Teachers in rural areas face many challenges in order to access professional learning equitable to their city counterparts. In the current climate, the Federal government of Australia is committed to initiatives that support the use of ICT in education. These include initiatives such as the Digital Education Revolution, including the National Broadband Network. This "revolution" includes the committal of $2.2 billion funding over six years from 2008 - 2013 which purports to bring substantial and meaningful change to teaching and learning in Australian schools. Of this funding, the Prime Minister (former Minister for Education), Julia Gillard, has committed $40 million of the total budget to ICT related professional development for teachers. But how will rural teachers ensure they get a piece of the PD pie? Access to professional learning is critical and isolation from colleagues, professional associations and support structures can affect the retention of teachers and in turn affect the sustainability of rural communities. This research paper describes the findings of the first phase of a study that investigates access to professional learning from rural and remote areas of Western Australia, the efficiencies of this approach including teacher perceptions and possible opportunities for improvement through the application of technologies. A survey instrument was administered and the results from104 principals and teachers within the Remote Teaching Service and the Country Teaching Program of the Department of Education and Training (WA) are discussed. Qualitative data was collected by semi-structured interviews and emailed questionnaires. Phase One findings highlight the principals and teachers? perceptions of their access to professional development opportunities, professional learning communities and their use of information and communication technologies (ICT) to bridge the gap

Enhancing professional learning for rural educators by rethinking connectedness

Impending changes in Australian education brings forth the expected transformation of teachers working in schools. Three key points for transforming Australian schools has been identified by Gillard (2008a) including the improvement of quality teaching, ensuring every child benefits and mandating transparency and accountability. A number of initiatives were considered to assist with such reform including the implementation of a Digital Education Revolution, the move to the Australian Curriculum and the implementation of a National Framework for Professional Standards for Teaching. As these transformative initiatives are rolled out to teachers across Australia, the equitable access to PD to support all teachers, regardless of their geographical location, is in question. In line with the literature, the author proposes the concept of delivering PD and accessing PD from regional and remote areas be reconsidered. This research paper will outline the findings from the study including travel time being significant and impacting on teachers personal time; limited relief teachers impacting on access to PD; promotion and teacher registration being explicitly linked to PD; professional learning communities being valued but often limited by small staff numbers; professional learning conducted in the local context being preferred; professional learning established at the teacher and school level being desirable; teachers being confident in using technology and accessing PD online if required; and social cohesiveness being valued and often limited by isolation. Further this research has culminated in the development of a conceptual framework that would facilitate improving the amount and variety of professional learning available to regional and remote teachers.

Rethinking connectedness: improving access to professional learning for regional and remote teachers

Transformation of Australian education is occurring at a rapid rate through the implementation of a number of initiatives. These initiatives include the Digital Education Revolution, the move to a National Curriculum and the implementation of a National Framework for Professional Standards for Teachers and Principals. As these initiatives are rolled out to schools across Australia, the equitable access to professional learning to support all teachers, regardless of their geographical location, is in question. A number of studies have been conducted in Australia that highlight the importance of professional learning and the difficulty faced by regional and remote teachers with regard to access (Gerard Daniels, 2007; Lysons, Cooksey, Panizzon, Parnell & Pegg 2006; Ministerial Review of Schooling, 1994, Rural and Remote Education Advisory Council, 2000; Vinson, 2002). Along with access to professional learning, has been the discussion of effective modes of delivery. Face to face professional learning, in regional and metropolitan areas, is offered in isolation, or in some cases, is complimented with virtual learning environments. The need for a more sustainable approach to professional learning is highly necessary. A mixed method research approach was utilised in order to answer the primary research question "In what ways might technology be used to support professional learning of regional and remote teachers in Western Australia?" This research paper outlines the findings from the study including the significance of travel time; impact of limited relief teachers; implications for promotion and teacher registration; professional learning communities being valued but often limited by small staff numbers; professional learning conducted in the local context being preferred; professional learning established at the teacher and school level being desirable; teachers being confident in using technology and accessing PD online if required; and social cohesiveness being valued and often limited by isolation. Further, this research has culminated in the development of a "model of rethinking connectedness" that would facilitate improving the amount and variety of professional learning available to regional and remote teachers.

Thymidine phosphorylase in cancer; Enemy or friend?

Thymidine phosphorylase (TP) is a nucleoside metabolism enzyme that plays an important role in the pyrimidine pathway.TP catalyzes the conversion of thymidine to thymine and 2-deoxy-α-D-ribose-1-phosphate (dRib-1-P). Although this reaction is reversible, the main metabolic function of TP is catabolic. TP is identical to the angiogenic factor platelet-derived endothelial-cell growth factor (PD-ECGF). TP is overexpressed in several human cancers in response to cellular stressful conditions like hypoxia, acidosis, chemotherapy and radiotherapy. TP has been shown to promote tumor angiogenesis, invasion, metastasis, evasion of the immune-response and resistance to apoptosis. Some of the biological effects of TP are dependent on its enzymatic activity, while others are mediated through cytokines like interleukin 10 (IL-10), basic fibroblast growth factor (bFGF) and tumour necrosis factor α (TNFα). Interestingly, TP also plays a role in cancer treatment through its role in the conversion of the oral fluoropyrimidine capecitabine into its active form 5-FU. TP is a predictive marker for fluoropyrimidine response. Given its various biological functions in cancer progression, TP is a promising target in cancer treatment. Further translational research is required in this area.

Stimulating immune responses to fight cancer: Basic biology and mechanisms

Chronic inflammation is now recognized as a major cause of malignant disease. In concert with various mechanisms (including DNA instability), hypoxia and activation of inflammatory bioactive lipid pathways and pro-inflammatory cytokines open the doorway to malignant transformation and proliferation, angiogenesis, and metastasis in many cancers. A balance between stimulatory and inhibitory signals regulates the immune response to cancer. These include inhibitory checkpoints that modulate the extent and duration of the immune response and may be activated by tumor cells. This contributes to immune resistance, especially against tumor antigen-specific T-cells. Targeting these checkpoints is an evolving approach to cancer immunotherapy, designed to foster an immune response. The current focus of these trials is on the programmed cell death protein 1 (PD-1) receptor and its ligands (PD-L1, PD-L2) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Researchers have developed anti-PD-1 and anti-PDL-1 antibodies that interfere with the ligands and receptor and allow the tumor cell to be recognized and attacked by tumor-infiltrating T-cells. These are currently being studied in lung cancer. Likewise, CTLA-4 inhibitors, which have had success treating advanced melanoma, are being studied in lung cancer with encouraging results.