Apples, Oranges and Lemons: The use and utility of administrative data in the Victorian legal assistance sector

This report examines how administrative data is collected and used in the Victorian legal assistance sector justice system. It investigates what data is available, its accuracy and consistency, how data is used and what needs to be done to improve its ability to answer access to justice questions. Findings show that administrative data in the legal assistance sector is used for many purposes in both useful and innovative ways, however there are challenges to using it system-wide for meaningful comparative analysis. Improving the consistency and accuracy of administrative data will help better answer access to justice questions. Strategies to help unlock the utility of administrative data include: improving data quality and standardising practices; enhancing data leadership, collaboration and coordination; investing in people and time; and dedicated funding for administrative data work

Major system change: a management and organisational research perspective. In Raine R, Fitzpatrick R, Barratt H, Bevan G, Black N, Boaden R, et al. Challenges, solutions and future directions in the evaluation of service innovations in health care and public health.

The scale and complexity of major system change in health care (typically involving multiple change processes, organisations and stakeholders) presents particular conceptual and methodological challenges for evaluation by researchers. This essay summarises some current approaches to evaluating major system change from the field of management and organisational research, and discusses conceptual and methodological questions for further developing the field. It argues that multilevel conceptual frameworks and mixed-methods approaches are required to capture the complexity and the heterogeneity of the mechanisms, processes and outcomes of major system change. Future evaluation designs should aim to represent key components of major system change – the context, processes and practices, and outcomes – by looking for ways that quantitative and qualitative methods can enrich one another. Related challenges in ensuring that findings from evaluating major system change are used by decision-makers to inform policy and practice are also discussed

Melting mud in Earth's mantle

Melting of subducted sediment remains controversial, as direct observation of sediment melt generation at mantle depths is not possible. Geochemical fingerprints provide indirect evidence for subduction delivery of sediment to the mantle; however, sediment abundance in mantle-derived melt is generally low (0%–2%), and difficult to detect. Here we provide evidence for melting of subducted sediment in granite sampled from an exhumed mantle section. Peraluminous granite dikes that intrude peridotite in the Oman–United Arab Emirates ophiolite have U-Pb ages of 99.8 ± 3.3 Ma that predate obduction. The dikes have unusually high oxygen isotope (δ18O) values for whole rock (14–23‰) and quartz (20–22‰), and yield the highest δ18O zircon values known (14–28‰; values relative to Vienna standard mean ocean water [VSMOW]). The extremely high oxygen isotope ratios uniquely identify the melt source as high-δ18O marine sediment (pelitic and/or siliciceous mud), as no other source could produce granite with such anomalously high δ18O. Formation of high-δ18O sediment-derived (S-type) granite within peridotite requires subduction of sediment to the mantle, where it melted and intruded overlying mantle wedge. The granite suite described here contains the highest oxygen isotope ratios reported for igneous rocks, yet intruded mantle peridotite below the Mohorovičić seismic discontinuity, the most primitive oxygen isotope reservoir in the silicate Earth. Identifying the presence and quantifying the extent of sediment melting within the mantle has important implications for understanding subduction recycling of supracrustal material and effects on mantle heterogeneity over time.National Geographi

A global perspective on marine photosynthetic picoeukaryote community structure

A central goal in ecology is to understand the factors affecting the temporal dynamics and spatial distribution of microorganisms and the underlying processes causing differences in community structure and composition. However, little is known in this respect for photosynthetic picoeukaryotes (PPEs), algae that are now recognised as major players in marine CO2 fixation. Here, we analysed dot blot hybridisation and cloning–sequencing data, using the plastid-encoded 16S rRNA gene, from seven research cruises that encompassed all four ocean biomes. We provide insights into global abundance, α- and β-diversity distribution and the environmental factors shaping PPE community structure and composition. At the class level, the most commonly encountered PPEs were Prymnesiophyceae and Chrysophyceae. These taxa displayed complementary distribution patterns, with peak abundances of Prymnesiophyceae and Chrysophyceae in waters of high (25:1) or low (12:1) nitrogen:phosphorus (N:P) ratio, respectively. Significant differences in phylogenetic composition of PPEs were demonstrated for higher taxonomic levels between ocean basins, using Unifrac analyses of clone library sequence data. Differences in composition were generally greater between basins (interbasins) than within a basin (intrabasin). These differences were primarily linked to taxonomic variation in the composition of Prymnesiophyceae and Prasinophyceae whereas Chrysophyceae were phylogenetically similar in all libraries. These data provide better knowledge of PPE community structure across the world ocean and are crucial in assessing their evolution and contribution to CO2 fixation, especially in the context of global climate change

Selective targeting of activating and inhibitory Smads by distinct WWP2 ubiquitin ligase isoforms differentially modulates TGFβ signalling and EMT

Ubiquitin-dependent mechanisms have emerged as essential regulatory elements controlling cellular levels of Smads and TGFß-dependent biological outputs such as epithelial–mesenchymal transition (EMT). In this study, we identify a HECT E3 ubiquitin ligase known as WWP2 (Full-length WWP2-FL), together with two WWP2 isoforms (N-terminal, WWP2-N; C-terminal WWP2-C), as novel Smad-binding partners. We show that WWP2-FL interacts exclusively with Smad2, Smad3 and Smad7 in the TGFß pathway. Interestingly, the WWP2-N isoform interacts with Smad2 and Smad3, whereas WWP2-C interacts only with Smad7. In addition, WWP2-FL and WWP2-C have a preference for Smad7 based on protein turnover and ubiquitination studies. Unexpectedly, we also find that WWP2-N, which lacks the HECT ubiquitin ligase domain, can also interact with WWP2-FL in a TGFß-regulated manner and activate endogenous WWP2 ubiquitin ligase activity causing degradation of unstimulated Smad2 and Smad3. Consistent with our protein interaction data, overexpression and knockdown approaches reveal that WWP2 isoforms differentially modulate TGFß-dependent transcription and EMT. Finally, we show that selective disruption of WWP2 interactions with inhibitory Smad7 can stabilise Smad7 protein levels and prevent TGFß-induced EMT. Collectively, our data suggest that WWP2-N can stimulate WWP2-FL leading to increased activity against unstimulated Smad2 and Smad3, and that Smad7 is a preferred substrate for WWP2-FL and WWP2-C following prolonged TGFß stimulation. Significantly, this is the first report of an interdependent biological role for distinct HECT E3 ubiquitin ligase isoforms, and highlights an entirely novel regulatory paradigm that selectively limits the level of inhibitory and activating Smads

Groups without cultured representatives dominate eukaryotic picophytoplankton in the oligotrophic South East Pacific Ocean

Background: Photosynthetic picoeukaryotes (PPE) with a cell size less than 3 µm play a critical role in oceanic primary production. In recent years, the composition of marine picoeukaryote communities has been intensively investigated by molecular approaches, but their photosynthetic fraction remains poorly characterized. This is largely because the classical approach that relies on constructing 18S rRNA gene clone libraries from filtered seawater samples using universal eukaryotic primers is heavily biased toward heterotrophs, especially alveolates and stramenopiles, despite the fact that autotrophic cells in general outnumber heterotrophic ones in the euphotic zone. Methodology/Principal Findings: In order to better assess the composition of the eukaryotic picophytoplankton in the South East Pacific Ocean, encompassing the most oligotrophic oceanic regions on earth, we used a novel approach based on flow cytometry sorting followed by construction of 18S rRNA gene clone libraries. This strategy dramatically increased the recovery of sequences from putative autotrophic groups. The composition of the PPE community appeared highly variable both vertically down the water column and horizontally across the South East Pacific Ocean. In the central gyre, uncultivated lineages dominated: a recently discovered clade of Prasinophyceae (IX), clades of marine Chrysophyceae and Haptophyta, the latter division containing a potentially new class besides Prymnesiophyceae and Pavlophyceae. In contrast, on the edge of the gyre and in the coastal Chilean upwelling, groups with cultivated representatives (Prasinophyceae clade VII and Mamiellales) dominated. Conclusions/Significance: Our data demonstrate that a very large fraction of the eukaryotic picophytoplankton still escapes cultivation. The use of flow cytometry sorting should prove very useful to better characterize specific plankton populations by molecular approaches such as gene cloning or metagenomics, and also to obtain into culture strains representative of these novel groups

Investing in updating: how do conclusions change when Cochrane systematic reviews are updated?

BACKGROUND: Cochrane systematic reviews aim to provide readers with the most up-to-date evidence on the effects of healthcare interventions. The policy of updating Cochrane reviews every two years consumes valuable time and resources and may not be appropriate for all reviews. The objective of this study was to examine the effect of updating Cochrane systematic reviews over a four year period. METHODS: This descriptive study examined all completed systematic reviews in the Cochrane Database of Systematic Reviews (CDSR) Issue 2, 1998. The latest version of each of these reviews was then identified in CDSR Issue 2, 2002 and changes in the review were described. For reviews that were updated within this time period and had additional studies, we determined whether their conclusion had changed and if there were factors that were predictive of this change. RESULTS: A total of 377 complete reviews were published in CDSR Issue 2, 1998. In Issue 2, 2002, 14 of these reviews were withdrawn and one was split, leaving 362 reviews to examine for the purpose of this study. Of these reviews, 254 (70%) were updated. Of these updated reviews, 23 (9%) had a change in conclusion. Both an increase in precision and a change in statistical significance of the primary outcome were predictive of a change in conclusion of the review. CONCLUSION: The concerns around a lack of updating for some reviews may not be justified considering the small proportion of updated reviews that resulted in a changed conclusion. A priority-setting approach to the updating of Cochrane systematic reviews may be more appropriate than a time-based approach. Updating all reviews as frequently as every two years may not be necessary, however some reviews may need to be updated more often than every two years

Age of diagnosis does not alter the presentation or progression of robustly defined adult onset type 1 diabetes

This is the author accepted manuscript. The final version is available from the American Diabetes Association via the DOI in this record OBJECTIVE: To determine whether presentation, progression, and genetic susceptibility of robustly defined adult-onset type 1 diabetes (T1D) are altered by diagnosis age. RESEARCH DESIGN AND METHODS: We compared the relationship between diagnosis age and presentation, C-peptide loss (annual change in urine C-peptide-creatinine ratio [UCPCR]), and genetic susceptibility (T1D genetic risk score [GRS]) in adults with confirmed T1D in the prospective StartRight study, 1,798 adults with new-onset diabetes. T1D was defined in two ways: two or more positive islet autoantibodies (of GAD antibody, IA-2 antigen, and ZnT8 autoantibody) irrespective of clinical diagnosis (n = 385) or one positive islet autoantibody and a clinical diagnosis of T1D (n = 180). RESULTS: In continuous analysis, age of diagnosis was not associated with C-peptide loss for either definition of T1D (P > 0.1), with mean (95% CI) annual C-peptide loss in those diagnosed before and after 35 years of age (median age of T1D defined by two or more positive autoantibodies): 39 (31-46) vs. 44% (38-50) with two or more positive islet autoantibodies and 43 (33-51) vs. 39% (31-46) with clinician diagnosis confirmed by one positive islet autoantibody (P > 0.1). Baseline C-peptide and T1D GRS were unaffected by age of diagnosis or T1D definition (P > 0.1). In T1D defined by two or more autoantibodies, presentation severity was similar in those diagnosed before and after 35 years of age: unintentional weight loss, 80 (95% CI 74-85) vs. 82% (76-87); ketoacidosis, 24 (18-30) vs. 19% (14-25); and presentation glucose, 21 (19-22) vs. 21 mmol/L (20-22) (all P ≥ 0.1). Despite similar presentation, older adults were less likely to be diagnosed with T1D, insulin-treated, or admitted to hospital. CONCLUSIONS: When adult-onset T1D is robustly defined, the presentation characteristics, progression, and T1D genetic susceptibility are not altered by age of diagnosis.Diabetes UKNational Institute for Health Research (NIHR)European Foundation for the Study of Diabete

Novel Role of Y1 Receptors in the Coordinated Regulation of Bone and Energy Homeostasis

The importance of neuropeptide Y (NPY) and Y2 receptors in the regulation of bone and energy homeostasis has recently been demonstrated. However, the contributions of the other Y recep- tors are less clear. Here we show that Y1 receptors are expressed on osteoblastic cells. Moreover, bone and adipose tissue mass are elevated in Y1/ mice with a generalized increase in bone formation on cortical and cancellous surfaces. Importantly, the inhibitory effects of NPY on bone marrow stromal cells in vitro are absent in cells derived from Y1/ mice, indicating a direct action of NPY on bone cells via this Y receptor. Interestingly, in contrast to Y2 receptor or germ line Y1 receptor deletion, con- ditional deletion of hypothalamic Y1 receptors in adult mice did not alter bone homeostasis, food intake, or adiposity. Further- more, deletion of both Y1 and Y2 receptors did not produce additive effects in bone or adiposity. Thus Y1 receptor pathways act powerfully to inhibit bone production and adiposity by non- hypothalamic pathways, with potentially direct effects on bone tissue through a single pathway with Y2 receptors