Victorian index of estuary condition : recommended themes and measures

Deakin University was engaged by the Department of Sustainability and Environment to develop an Index of Estuary Condition (IEC) for evaluating the environmental condition of Victorian estuaries. The Index will ultimately complement the existing Index of Stream Condition (ISC) by providing a consistent statewide assessment of the environmental condition of estuaries. This will better enable:&bull; Estuarine condition to be reported at regional, state and national levels.&bull; Prioritisation of resource allocation.&bull; Strategic evaluation of management interventions in estuaries.Workshops involving participants with expertise in a variety of disciplines were convened to integrate learnings from assessment programs currently being developed interstate and overseas. This report synthesises and builds on the output from those workshops which: &bull; Identified key components (themes) of estuaries that contribute to estuarine condition. &bull; Contributed to development of a broad conceptual model for Victorian estuaries &bull; Identified possible measures of each themeIn keeping with the sub-indices of the ISC, six themes were identified for use in the IEC: Physical form, Hydrology, Water quality, Sediment, Flora and Fauna. Several measures within each theme are recommended to assess estuary condition.Implementation of particular measures in the IEC partly depends on the investment required to both collect and interpret the required data. With regard to data collection, each measure was assessed according to whether there is an established sampling procedure, how frequently data need to be collected and the level of expertise required for collection and processing. For interpreting the data, measures were scored on whether baseline condition is established and whether descriptions and scores are developed which reflect the extent of deviation from that condition. These scores were used to indicate which measures are feasible to implement immediately and which require further investigation. A trial of the recommended IEC measures in a selection of estuaries is recommended as it would provide an opportunity to test the measures and their suitability for application statewide. It is suggested that the trial is conducted in estuaries subject to various levels of threats within each of the four estuary classes described by Barton et al. (2008)<br /

Diagnostic accuracy of DXA compared to conventional spine radiographs for the detection of vertebral fractures in children

Objectives In children, radiography is performed to diagnose vertebral fractures and dual energy x-ray absorptiometry (DXA) to assess bone density. In adults, DXA assesses both. We aimed to establish whether DXA can replace spine radiographs in assessment of paediatric vertebral fractures. Methods Prospectively, lateral spine radiographs and lateral spine DXA of 250 children performed on the same day were independently scored by three radiologists using the simplified algorithm based qualitative technique and blinded to results of the other modality. Consensus radiograph read and second read of 100 random images were performed. Diagnostic accuracy, inter/intraobserver and intermodality agreements, patient/carer experience and radiation dose were assessed. Results Average sensitivity and specificity (95% confidence interval) in diagnosing one or more vertebral fractures requiring treatment was 70% (58%-82%) and 97% (94%- 100%) respectively for DXA and 74% (55%-93%) and 96% (95%-98%) for radiographs. Fleiss’ kappa for interobserver and average kappa for intraobserver reliability were 0.371 and 0.631 respectively for DXA and 0.418 and 0.621 for radiographs. Average effective dose was 41.9µSv for DXA and 232.7µSv for radiographs. Image quality was similar. Conclusion Given comparable image quality and non-inferior diagnostic accuracy, lateral spine DXA should replace conventional radiographs for assessment of vertebral fractures in children

Osteogenesis imperfecta: Ultrastructural and histological findings on examination of skin revealing novel insights into genotype-phenotype correlation

© 2016 Taylor & Francis. Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity to fracture. Over 90% of patients with OI have a mutation in COL1A1/COL1A2, which shows an autosomal dominant pattern of inheritance. In-depth phenotyping and in particular, studies involving manifestations in the skin connective tissue have not previously been undertaken in OI. The aims of the study were to perform histological and ultrastructural examination of skin biopsies in a cohort of patients with OI; to identify common and distinguishing features in order to inform genotype-phenotype correlation; and to identify common and distinguishing features between the different subtypes of OI. As part of the RUDY (Rare Diseases in Bone, Joints and/or Blood Vessels) study, in collaboration with the NIHR Rare Diseases Translational Research Collaboration, we undertook a national study of skin biopsies in patients with OI. We studied the manifestations in the skin connective tissue and undertook in-depth clinical and molecular phenotyping of 16 patients with OI. We recruited 16 patients: analyses have shown that in type 1 collagen mutation positive patients (COL1A1/ COL1A2) (n-4/16) consistent findings included: variable collagen fibril diameter (CFD) and presence of collagen flowers. Histological examination in these patients showed an increase in elastic fibers that are frequently fragmented and clumped. These observations provide evidence that collagen flowers and CFD variability are consistent features in OI due to type 1 collagen defects and reinforce the need for accurate phenotyping in conjunction with genomic analyses

Expanding the phenotype of SPARC-related osteogenesis imperfecta: clinical findings in two patients with pathogenic variants in SPARC and literature review

BACKGROUND: Secreted protein, acidic, cysteine rich (SPARC)-related osteogenesis imperfecta (OI), also referred to as OI type XVII, was first described in 2015, since then there has been only one further report of this form of OI. SPARC is located on chromosome 5 between bands q31 and q33. The encoded protein is necessary for calcification of the collagen in bone, synthesis of extracellular matrix and the promotion of changes to cell shape. METHODS: We describe a further two patients with previously unreported homozygous SPARC variants with OI: one splice site; one nonsense pathogenic variant. We present detailed information on the clinical and radiological phenotype and correlate this with their genotype. There are only two previous reports by Mendozo-Londono et al and Hayat et al with clinical descriptions of patients with SPARC variants. RESULTS: From the data we have obtained, common clinical features in individuals with OI type XVII caused by SPARC variants include scoliosis (5/5), vertebral compression fractures (5/5), multiple long bone fractures (5/5) and delayed motor development (3/3). Interestingly, 2/4 patients also had abnormal brain MRI, including high subcortical white matter changes, abnormal fluid-attenuated inversion in the para-atrial white matter and a large spinal canal from T10 to L1. Of significance, both patients reported here presented with significant neuromuscular weakness prompting early workup. CONCLUSION: Common phenotypic expressions include delayed motor development with neuromuscular weakness, scoliosis and multiple fractures. The data presented here broaden the phenotypic spectrum establishing similar patterns of neuromuscular presentation with a presumed diagnosis of 'myopathy'

Small firms and patenting revisited

In order to observe a patent application at the firm level two conditions need to be met: new products need to be of patentable quality, which depends both on the degree of novelty of innovations and on the total number (portfolio) of innovations; and the benefits of patents need to be higher than the costs of owning them. Analyzing the patent propensity of small and large UK firms using a novel innovation-level survey (the SIPU survey) linked to Community Innovation Survey data we find that when we consider the whole innovation portfolio smaller firms do patent less than larger firms. However, using data on individual innovations, we find that smaller firms are no less likely to patent any specific innovation than larger firms. We argue that size differences in the probability to patent relate primarily to the ‘portfolio effect’, i.e. larger firms generate more innovations than smaller firms and therefore are more likely to create one or more which are patentable. As for the decision to patent a patentable innovation, we find that cost barriers, more than issues of innovation quality or enforceability, deter small firms from patenting specific innovations. Measures to address the costs of patenting for smaller firms – perhaps by considering patents as eligible costs for R&D tax credits – and/or subsidizing SMEs’ participation in IP litigation schemes may both encourage patent use by smaller firms

Atypical osteogenesis imperfecta caused by a 17q21.33 deletion involving COL1A1.

The majority of patients with osteogenesis imperfecta (OI) have a mutation in COL1A1 or COL1A2. Whole gene deletions appear to be an infrequent cause of OI. Here we describe a 8-year-old female with OI, intellectual disability and behavioural problems caused by a 2.3Mb deletion of chromosome 17q21.33 containing COL1A1. This deletion was detected using array comparative genomic hybridization (aCGH), performed to identify a cause for her intellectual disability. DLX3, DLX4, CA10, CACNA1G, ITGA3 and XYLT2 were also deleted and likely to be contributing to her phenotype. This case provides further evidence that aCGH is an important test for children with OI when it is associated with additional features, such as intellectual or behavioural disability. With greater use of aCGH, the proportion of patients with atypical OI due to contiguous gene deletions or copy number variation elsewhere in the genome is likely to become clearer. This case also provides evidence that deletions in COL1A1 resulting in haploinsuffiency are pathogenic and that a contiguous gene deletion may modify the patient’s phenotype

Successful recruitment to trials: findings from the SCIMITAR plus Trial

BACKGROUND: Randomised controlled trials (RCT) can struggle to recruit to target on time. This is especially the case with hard to reach populations such as those with severe mental ill health. The SCIMITAR+ trial, a trial of a bespoke smoking cessation intervention for people with severe mental ill health achieved their recruitment ahead of time and target. This article reports strategies that helped us to achieve this with the aim of aiding others recruiting from similar populations. METHODS: SCIMITAR+ is a multi-centre pragmatic two-arm parallel-group RCT, which aimed to recruit 400 participants with severe mental ill health who smoke and would like to cut down or quit. The study recruited primarily in secondary care through community mental health teams and psychiatrists with a smaller number of participants recruited through primary care. Recruitment opened in October 2015 and closed in December 2016, by which point 526 participants had been recruited. We gathered information from recruiting sites on strategies which led to the successful recruitment in SCIMITAR+ and in this article present our approach to trial management along with the strategies employed by the recruiting sites. RESULTS: Alongside having a dedicated trial manager and trial management team, we identified three main themes that led to successful recruitment. These were: clinicians with a positive attitude to research; researchers and clinicians working together; and the use of NHS targets. The overriding theme was the importance of relationships between both the researchers and the recruiting clinicians and the recruiting clinicians and the participants. CONCLUSIONS: This study makes a significant contribution to the limited evidence base of real-world cases of successful recruitment to RCTs and offers practical guidance to those planning and conducting trials. Building positive relationships between clinicians, researchers and participants is crucial to successful recruitment