Natural history of corneal nerve morphology in mild neuropathy associated with type 1 diabetes : Development of a potential measure of diabetic peripheral neuropathy

Purpose To investigate longitudinal changes of subbasal nerve plexus (SNP) morphology and its relationship with conventional measures of neuropathy in individuals with diabetes. Methods A cohort of 147 individuals with type 1 diabetes and 60 age-balanced controls underwent detailed assessment of clinical and metabolic factors, neurologic deficits, quantitative sensory testing, nerve conduction studies and corneal confocal microscopy at baseline and four subsequent annual visits. The SNP parameters included corneal nerve fiber density (CNFD), branch density (CNBD) and fiber length (CNFL) and were quantified using a fully-automated algorithm. Linear mixed models were fitted to examine the changes in corneal nerve parameters over time. Results At baseline, 27% of the participants had mild diabetic neuropathy. All SNP parameters were significantly lower in the neuropathy group compared to controls (P<0.05). Overall, 89% of participants examined at baseline also completed the final visit. There was no clinically significant change to health and metabolic parameters and neuropathy measures from baseline to the final visit. Linear mixed model revealed a significant linear decline of CNFD (annual change rate, -0.9 nerve/mm2, P=0.01) in the neuropathy group compared to controls, which was associated with age (β=-0.06, P=0.04) and duration of diabetes (β=-0.08, P=0.03). In the neuropathy group, absolute changes of CNBD and CNFL showed moderate correlations with peroneal conduction velocity and cold sensation threshold, respectively (rs, 0.38 and 0.40, P<0.05). Conclusion This study demonstrates dynamic small fiber damage at the SNP, thus providing justification for our ongoing efforts to establish corneal nerve morphology as an appropriate adjunct to conventional measures of DPN.

Corneal confocal microscopy shown an improvement in small-fibre neuropathy in subjects with type 1 diabetes on continuous subcutaneous insulin infusion compared to multiple daily injection

Improved glycemic control is the only treatment that has been shown to be effective for diabetic peripheral neuropathy in patients with type 1 diabetes (1). Continuous subcutaneous insulin infusion (CSII) is superior to multiple daily insulin injection (MDI) for reducing HbA1c and hypoglycemic events (2). Here, we have compared the benefits of CSII compared withMDI for neuropathy over 24months....

Perceived needs for supported self-management of type 2 diabetes : a qualitative investigation of the potential for a web-based intervention

The estimated one million Australians with type 2 diabetes face significant risks of morbidity and premature mortality. Inadequate diabetes self-management is associated with poor glycaemic control, which is further impaired by comorbid dysphoria. Regular access to ongoing self-management and psychological support is limited, especially in rural and regional locations. Web-based interventions can provide complementary support to patients’ usual care. Semi-structured interviews were undertaken with two samples that comprised (a) 13 people with type 2 diabetes and (b) 12 general practitioners (GPs). Interviews explored enablers and barriers to self-care, emotional challenges, needs for support, and potential web-based programme components. Patients were asked about the potential utility of a web-based support programme, and GPs were asked about likely circumstances of patient referral to it. Thematic analysis was used to summarise responses. Most perceived facilitators and barriers to self-management were similar across the groups. Both groups highlighted the centrality of dietary self-management, valued shared decision-making with health professionals, and endorsed the idea of web-based support. Some emotional issues commonly identified by patients varied to those perceived by GPs, resulting in different attributions for impaired self-care. A web-based programme that supported self-management and psychological/emotional needs appears likely to hold promise in yielding high acceptability and perceived utility.

The OnTrack Diabetes web-based program for type 2 diabetes and dysphoria self-management: A randomized controlled trial protocol

Background: The prevalence of type 2 diabetes is rising with the majority of patients practicing inadequate disease self-management. Depression, anxiety, and diabetes-specific distress present motivational challenges to adequate self-care. Health systems globally struggle to deliver routine services that are accessible to the entire population, in particular in rural areas. Web-based diabetes self-management interventions can provide frequent, accessible support regardless of time and location Objective: This paper describes the protocol of an Australian national randomized controlled trial (RCT) of the OnTrack Diabetes program, an automated, interactive, self-guided Web program aimed to improve glycemic control, diabetes self-care, and dysphoria symptoms in type 2 diabetes patients. Methods: A small pilot trial is conducted that primarily tests program functionality, efficacy, and user acceptability and satisfaction. This is followed by the main RCT, which compares 3 treatments: (1) delayed program access: usual diabetes care for 3 months postbaseline followed by access to the full OnTrack Diabetes program; (2) immediate program: full access to the self-guided program from baseline onward; and (3) immediate program plus therapist support via Functional Imagery Training (FIT). Measures are administered at baseline and at 3, 6, and 12 months postbaseline. Primary outcomes are diabetes self-care behaviors (physical activity participation, diet, medication adherence, and blood glucose monitoring), glycated hemoglobin A1c (HbA1c) level, and diabetes-specific distress. Secondary outcomes are depression, anxiety, self-efficacy and adherence, and quality of life. Exposure data in terms of program uptake, use, time on each page, and program completion, as well as implementation feasibility will be conducted. Results: This trial is currently underway with funding support from the Wesley Research Institute in Brisbane, Australia. Conclusions: This is the first known trial of an automated, self-guided, Web-based support program that uses a holistic approach in targeting both type 2 diabetes self-management and dysphoria. Findings will inform the feasibility of implementing such a program on an ongoing basis, including in rural and regional locations.

Graphene-type sheets of Nb1-xWxS2 : synthesis and in situ functionalization

Enlightened by the discovery of graphenes, a variety of inorganic analogues have been synthesized and characterized in recent years. Solvated Nb1-xWxS2 analogues of graphene-type sheets were prepared by lithiation and exfoliation of multistacked Nb1-xWxS2 coin roll nanowires (CRNWs), followed by in situ functionalization with gold nanoparticles to synthesize gold-loaded Nb1-xWxS2/Au nanocomposites. The Nb1-xWxS2 nanosheets and the corresponding Nb1-xWxS2/Au nanocomposites were characterized by high resolution electron microscopy (HRTEM), energy-dispersive X-ray spectroscopy (EDX), scanning transmission electron microscopy (STEM), dynamic light scattering (DLS) and scanning force microscopy (AFM). The graphene-type sheets are stable in water and other solvents and can be functionalized similarly as chalcogen-terminated surfaces (e.g. with Au nanoparticles).

Robust clustering of multi-type relational data via a heterogeneous manifold ensemble

High-Order Co-Clustering (HOCC) methods have attracted high attention in recent years because of their ability to cluster multiple types of objects simultaneously using all available information. During the clustering process, HOCC methods exploit object co-occurrence information, i.e., inter-type relationships amongst different types of objects as well as object affinity information, i.e., intra-type relationships amongst the same types of objects. However, it is difficult to learn accurate intra-type relationships in the presence of noise and outliers. Existing HOCC methods consider the p nearest neighbours based on Euclidean distance for the intra-type relationships, which leads to incomplete and inaccurate intra-type relationships. In this paper, we propose a novel HOCC method that incorporates multiple subspace learning with a heterogeneous manifold ensemble to learn complete and accurate intra-type relationships. Multiple subspace learning reconstructs the similarity between any pair of objects that belong to the same subspace. The heterogeneous manifold ensemble is created based on two-types of intra-type relationships learnt using p-nearest-neighbour graph and multiple subspaces learning. Moreover, in order to make sure the robustness of clustering process, we introduce a sparse error matrix into matrix decomposition and develop a novel iterative algorithm. Empirical experiments show that the proposed method achieves improved results over the state-of-art HOCC methods for FScore and NMI.

Adaptive finite element analysis of elliptic problems based on bubble-type local mesh generation

A new mesh adaptivity algorithm that combines a posteriori error estimation with bubble-type local mesh generation (BLMG) strategy for elliptic differential equations is proposed. The size function used in the BLMG is defined on each vertex during the adaptive process based on the obtained error estimator. In order to avoid the excessive coarsening and refining in each iterative step, two factor thresholds are introduced in the size function. The advantages of the BLMG-based adaptive finite element method, compared with other known methods, are given as follows: the refining and coarsening are obtained fluently in the same framework; the local a posteriori error estimation is easy to implement through the adjacency list of the BLMG method; at all levels of refinement, the updated triangles remain very well shaped, even if the mesh size at any particular refinement level varies by several orders of magnitude. Several numerical examples with singularities for the elliptic problems, where the explicit error estimators are used, verify the efficiency of the algorithm. The analysis for the parameters introduced in the size function shows that the algorithm has good flexibility.

Patient perspectives of using a web based intervention program for patients with type 2 diabetes and acute coronary syndrome

Introduction Research highlights patients with dual diagnoses of type 2 diabetes and acute coronary syndrome (ACS) have higher readmission rates and poorer health outcomes than patients with singular chronic conditions. Despite this, there is a lack of education programs targeted for this dual diagnosis population to improve self-management and decrease negative health outcomes. There is evidence to suggest that internet based interventions may improve health outcomes for patients with singular chronic conditions, however there is a need to develop an evidence base for ACS patients with comorbid diabetes. There is a growing awareness of the importance of a participatory model in developing effective online interventions. That is, internet interventions are more effective if end users’ perceptions of the intervention are incorporated in their final development prior to testing in large scale trials. Objectives This study investigated patients’ perspectives of the web-based intervention designed to promote self-management of the dual conditions in order to refine the intervention prior to clinical trial evaluation. Methods An interpretive approach with thematic analysis was used to obtain deeper understanding regarding participants’ experience when using web-application interventions for patients with ACS and type 2 diabetes. Semi-structured interviews were undertaken on a purposive sample of 30 patients meeting strict inclusion and exclusion criteria to obtain their perspectives on the program. Results Preliminary results indicate patients with dual diagnoses express more complex needs than those with a singular condition. Participants express a positive experience with the proposed internet intervention and emerging themes include that the web page is seen as easy to use and comforting as a support, in that patients know they are not alone. Further results will be reported as they become available. Conclusion The results indicate potential for patient acceptability of the newly developed internet intervention for patients with ACS and comorbid diabetes. Incorporation of patient perspectives into the final development of the intervention is likely to maximise successful outcomes of any future trials that utilise this intervention. Future quantitative evaluation of the effectiveness of the intervention is being planned.

Biology Aotearoa : Unique Flora, Fauna and Fungi

As a large, isolated and relatively ancient landmass, New Zealand occupies a unique place in the biological world, with distinctive terrestrial biota and a high proportion of primitive endemic forms. Biology Aotearoa covers the origins, evolution and conservation of the New Zealand flora, fauna and fungi. Each chapter is written by specialists in the field, often working from different perspectives to build up a comprehensive picture. Topics include: the geological history of our land origins, and evolution of our plants, animals and fungi current status of rare and threatened species past, present and future management of native species the effect of human immigration on the native biota. Colour diagrams and photographs are used throughout the text. This book is suitable for all students of biology or ecology who wish to know about the unique nature of Aotearoa New Zealand and its context in the biological world.

Diversity of New Zealand's Terrestrial and Freshwater Fauna

As a large, isolated and relatively ancient landmass, New Zealand occupies a unique place in the biological world, with distinctive terrestrial biota and a high proportion of primitive endemic forms. Biology Aotearoa covers the origins, evolution and conservation of the New Zealand flora, fauna and fungi. Each chapter is written by specialists in the field, often working from different perspectives to build up a comprehensive picture. Topics include: the geological history of our land origins, and evolution of our plants, animals and fungi current status of rare and threatened species past, present and future management of native species the effect of human immigration on the native biota.

Identification and characterization of novel proteolytic interactions of prostate cancer-expressed kallikrein-related peptidases, type II transmembrane serine proteases and matrix metalloproteinases

This study investigated interactions of protein-cleaving enzymes (or proteases) that promote prostate cancer progression. It provides the first evidence of a novel regulatory network of protease activity at the surface of cells. The proteases kallikrein-related peptidases 4 and 14, and matrix metalloproteinases 3 and 9 are cleaved at the cell surface by the cell surface proteases hepsin and TMPRSS2. These cleavage events potentially regulate activation of downstream targets of kallikrein 4 and 14 such as cell surface signalling via the protease-activated receptors (PARs) and cell growth-promoting factors such as hepatocyte-growth factor.

Does school type affect cognitive and non-cognitive development in children? Evidence from Australian primary schools

This paper investigates the effects of primary school choices on cognitive and non-cognitive development in children using data from the Longitudinal Study of Australian Children (LSAC). We militate against the measurement problems that are associated with individual unobserved heterogeneity by exploiting the richness of LSAC data and applying contemporary econometric approaches. We find that sending children to Catholic or other independent primary schools has no significant effect on their cognitive and non-cognitive outcomes. The literature now has evidence from three different continents that the returns to attending Catholic primary schools are no different than public schools.

Cell type-dependent, infection-induced, aberrant DNA methylation in gastric cancer

Epigenetic changes correspond to heritable modifications of the chromatin structure, which do not involve any alteration of the DNA sequence but nonetheless affect gene expression. These mechanisms play an important role in cell differentiation, but aberrant occurrences are also associated with a number of diseases, including cancer and neural development disorders. In particular, aberrant DNA methylation induced by H. Pylori has been found to be a significant risk factor in gastric cancer. To investigate the sensitivity of different genes and cell types to this infection, a computational model of methylation in gastric crypts is developed. In this article, we review existing results from physical experiments and outline their limitations, before presenting the computational model and investigating the influence of its parameters.

Beyond Moa's Ark and Wallace's Line: extralimital distribution of new species of Austronothrus (Acari, Oribatida, Crotoniidae) and the endemicity of the New Zealand oribatid mite fauna

The genus Austronothrus was previously known from three species recorded only from New Zealand. Austronothrus kinabalu sp. nov. is described from Sabah, Borneo and A. rostralis sp. nov. from Norfolk Island, south-west Pacific. A key to Austronothrus is included. These new species extend the distribution of Austronothrus beyond New Zealand and confirms that the subfamily Crotoniinae is not confined to former Gondwanan landmasses. The distribution pattern of Austronothrus spp., combining Oriental and Gondwanan localities, is indicative of a curved, linear track; consistent with the accretion of island arcs and volcanic terranes around the plate margins of the Pacific Ocean, with older taxa persisting on younger island though localised dispersal within island arc metapopulations. Phylogenetic analysis and an area cladogram are consistent with a broad ancestral distribution of Austronothrus in the Oriental region and on Gondwanan terranes, with subsequent divergence and distribution southward from the Sunda region to New Zealand. This pattern is more complex than might be expected if the New Zealand oribatid fauna was derived from dispersal following re-emergence of land after inundation during the Oligocene (25 mya), as well as if the fauna emanated from endemic, relictual taxa following separation of New Zealand from Gondwana during the Cretaceous (80 mya).