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Objectives: To assess glycaemic control, anthropometry and insulin regimens in a national sample of Australian children and adolescents with type 1 diabetes., Design: Cross-sectional analysis of de-identified, prospectively collected data from the Australasian Diabetes Data Network (ADDN) registry., Setting: Five paediatric diabetes centres in New South Wales, Queensland, South Australia, Victoria and Western Australia., Participants: Children and adolescents (aged 18 years or under) with type 1 diabetes of at least 12 months' duration for whom data were added to the ADDN registry during 2015., Main Outcome Measures: Glycaemic control was assessed by measuring haemoglobin A1c (HbA1c) levels. Body mass index standard deviation scores (BMI-SDS) were calculated according to the CDC-2000 reference; overweight and obesity were defined by International Obesity Task Force guidelines. Insulin regimens were classified as twice-daily injections (BD), multiple daily injections (MDI; at least three injection times per day), or continuous subcutaneous insulin infusion (CSII)., Results: The mean age of the 3279 participants was 12.8 years (SD, 3.7), mean diabetes duration was 5.7 years (SD, 3.7), and mean HbA1c level 67 mmol/mol (SD, 15); only 27% achieved the national HbA1c target of less than 58 mmol/mol. The mean HbA1c level was lower in children under 6 (63 mmol/mol) than in adolescents (14-18 years; 69 mmol/mol). Mean BMI-SDS for all participants was 0.6 (SD, 0.9); 33% of the participants were overweight or obese. 44% were treated with CSII, 38% with MDI, 18% with BD., Conclusions: Most Australian children and adolescents with type 1 diabetes are not meeting the recognised HbA1c target. The prevalence of overweight and obesity is high. There is an urgent need to identify barriers to achieving optimal glycaemic control in this population.

Record linkage is a technique for integrating data from sources or providers where direct access to the data is not possible due to security and privacy considerations. This is a very common scenario for medical data, as patient privacy is a significant concern. To avoid privacy leakage, researchers have adopted k-anonymity to protect raw data from re-identification however they cannot avoid associated information loss, e.g. due to generalisation. Given that individual-level data is often not disclosed in the linkage cases, but yet remains potentially re-discoverable, we propose semantic-based linkage k-anonymity to de-identify record linkage with fewer generalisations and eliminate inference disclosure through semantic reasoning.

Australasia is a region with a high incidence of type 1 diabetes (T1D). There are approximately 140 000 individuals with T1D, and of these 10 000 are children. Although the region covers a huge geographical area, most children with T1D are managed by tertiary academic centers in the major capital cities. Local longitudinal data collection has been in place for several decades in most of these centers, however ongoing national data collection had not been attempted. In 2012, with funding from the Juvenile Diabetes Research Foundation (JDRF) Australian Type 1 Clinical Research Network, a national collaboration was formed to provide ongoing longitudinal collection of T1D patient characteristics and outcomes. The initial phase of this collaboration, known as the Australasian Diabetes Data Network or ADDN, was led by the Australasian Paediatric Endocrine Group (APEG) and thus included only children and adolescents. The next phase, commenced in 2016, will see adult sites added through collaboration with the Australian Diabetes Society (ADS). As most of the initial centers had longitudinal data collection in place the model employed was to establish the transfer and collation of data already collected into a central database. This required the definition of a common data dictionary, ethics and governance procedures and the employment of technology to enable efficient and accurate information transfer and accessibility. The ADDN project received widespread support from the diabetes research community with study investigators representing 20 pediatric centers across the region. The first phase focused on the 5 largest centers and at the end of 2015 these centers were uploading patient data to the ADDN database on a quarterly basis resulting in 5271 patients with 83 506 diabetes visits., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2016 Diabetes Technology Society.)

Angiogenesis is essential for tumor growth and metastasis. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor predominantly expressed in steroidogenic organs like the adrenal gland, ovary, testes, and placenta. EG-VEGF has antiapoptotic, mitogenic, and chemoattractive properties mediated via the two G protein-coupled receptors prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2). We investigated the expression of EG-VEGF and its receptors in a large number of normal adrenal glands (NAG), adrenocortical adenomas (ACA), and carcinomas (ACC) using real-time PCR (NAG, n = 12; ACA, n = 24; and ACC, n = 30) and immunohistochemistry (NAG, n = 9; ACA, n = 23; and ACC, n = 163) and evaluated its impact on patients' survival. EG-VEGF, PKR1, and PKR2 mRNA and protein are expressed in NAG and the vast majority of ACA and ACC samples. The mean EG-VEGF mRNA expression was significantly lower in ACC (606.5 ± 77.1 copies) compared to NAG (4,043 ± 1,111) and cortisol-producing adenomas (CPA) (4,433 ± 2,378) (p < 0.01 and p < 0.05, respectively). However, cytoplasmic and nuclear EG-VEGF protein expression was either significantly higher or similar in ACC (H score 2.4 ± 0.05, p < 0.05 and 1.7 ± 0.08, n.s., respectively) compared to NAG (1.8 ± 0.14 and 1.7 ± 0.2). Nuclear protein expression of either EG-VEGF or PKR1 or both is predictive for a higher mortality compared to patients without nuclear expression (hazard ratio (HR) = 5.15; 95% confidence interval (CI) = 1.24-21.36, n = 100, p = 0.02 independent of age, sex, and tumor stage). These findings suggest that EG-VEGF and its receptor PKR1 might play a role in the pathogenesis of adrenocortical tumors and could serve as prognostic markers for this rare malignant disease.

Background and Objective: It is unclear whether the proportion of infants with a disorder of sex development who are raised as male or female has changed over time. The temporal trends in sex assignment of affected cases entered in the International Disorder of Sex Development (I-DSD) Registry were studied., Methods: Cases of disorders of sex development reported as partial androgen insensitivity syndrome (PAIS; n = 118), disorder of gonadal development (DGD; n = 232), and disorder of androgen synthesis (DAS; n = 104) were divided into those who were born before 1990, 1990-1999, and after 1999. External appearance of the genitalia was described by the external masculinization score., Results: The median (5th-95th percentile) external masculinization scores of those infants with PAIS, DGD, and DAS who were raised as boys were 6 (2-9), 6 (3-9), and 6 (1-12), respectively, and were significantly higher than in those raised as girls (2 [0-6], 2 [0-7], and 0 [0-5], respectively); this difference was maintained in the 3 temporal birth cohorts (P < .01). Of the 118 cases in the pre-1990 cohort, 41 (35%) were raised as boys; of the 148 cases in the 1990-1999 cohort, 60 (41%) were raised as boys; and of the 188 cases in the post-1999 cohort, 128 (68%) were raised as boys., Conclusions: Although there is an association between the external appearance of the genitalia and the choice of sex assignment, there are clear temporal trends in this practice pointing toward an increased likelihood of affected infants being raised as boys. The impact of this change in practice on long-term health outcomes requires additional focus., (Copyright © 2014 by the American Academy of Pediatrics.)

Context: The focus of care in disorders of sex development (DSD) is often directed to issues related to sex and gender development. In addition, the molecular etiology remains unclear in the majority of cases., Objective: To report the range of associated conditions identified in the international DSD (I-DSD) Registry., Design, Setting, and Patients: Anonymized data were extracted from the I-DSD Registry for diagnosis, karyotype, sex of rearing, genetic investigations, and associated anomalies. If necessary, clarification was sought from the reporting clinician., Results: Of 649 accessible cases, associated conditions occurred in 168 (26%); 103 (61%) cases had one condition, 31 (18%) had two conditions, 20 (12%) had three conditions, and 14 (8%) had four or more conditions. Karyotypes with most frequently reported associations included 45,X with 6 of 8 affected cases (75%), 45,X/46,XY with 19 of 42 cases (45%), 46,XY with 112 of 460 cases (24%), and 46,XX with 27 of 121 cases (22%). In the 112 cases of 46,XY DSD, the commonest conditions included small for gestational age in 26 (23%), cardiac anomalies in 22 (20%), and central nervous system disorders in 22 (20%), whereas in the 27 cases of 46,XX DSD, skeletal and renal anomalies were commonest at 12 (44%) and 8 (30%), respectively. Of 170 cases of suspected androgen insensitivity syndrome, 19 (11%) had reported anomalies and 9 of these had confirmed androgen receptor mutations., Conclusions: Over a quarter of the cases in the I-DSD Registry have an additional condition. These associations can direct investigators toward novel genetic etiology and also highlight the need for more holistic care of the affected person.

The very nature of rare diseases means that information is often sparse and highly distributed, and as a result progress in the field is more challenging to conduct. ENSAT-CANCER is an EU-FP7 funded initiative to develop a virtual research environment (VRE) offering a digitally interconnected infrastructure for distributed clinicians specialising in rare adrenal tumours to communicate and collaborate with distributed biomedical research communities. The core of the VRE is a registry that holds vital patient information from specialist centres around Europe, covering different types of adrenal tumours. The VRE also hosts a range of other enabling services including sample barcoding, bio-sample exchange mechanisms, an integrated linkage scheme to other trials and studies, summary statistics and report generation, image hosting - all of which are available in a seamless, security-driven environment. This paper presents the key challenges of this endeavour, the technical solutions that have been developed to address them and reporting the uptake and adoption of the work (currently at 2472 patient records and rising).

Applications of simulation modelling in social science domains are varied and increasingly widespread. The effective deployment of simulation models depends on access to diverse datasets, the use of analysis capabilities, the ability to visualize model outcomes and to capture, share and re-use simulations as evidence in research and policy-making. We describe three applications of e-social science that promote social simulation modelling, data management and visualization. An example is outlined in which the three components are brought together in a transport planning context. We discuss opportunities and benefits for the combination of these and other components into an e-infrastructure for social simulation and review recent progress towards the establishment of such an infrastructure.

The project Meeting the Design Challenges of nano-CMOS Electronics (http://www.nanocmos.ac.uk) was funded by the Engineering and Physical Sciences Research Council to tackle the challenges facing the electronics industry caused by the decreasing scale of transistor devices, and the inherent variability that this exposes in devices and in the circuits and systems in which they are used. The project has developed a grid-based solution that supports the electronics design process, incorporating usage of large-scale high-performance computing (HPC) resources, data and metadata management and support for fine-grained security to protect commercially sensitive datasets. In this paper, we illustrate how the nano-CMOS (complementary metal oxide semiconductor) grid has been applied to optimize transistor dimensions within a standard cell library. The goal is to extract high-speed and low-power circuits which are more tolerant of the random fluctuations that will be prevalent in future technology nodes. Using statistically enhanced circuit simulation models based on three-dimensional atomistic device simulations, a genetic algorithm is presented that optimizes the device widths within a circuit using a multi-objective fitness function exploiting the nano-CMOS grid. The results show that the impact of threshold voltage variation can be reduced by optimizing transistor widths, and indicate that a similar method could be extended to the optimization of larger circuits.

Many e-Health strategies rely on the secure integration of datasets that have previously resided in isolated locations, but can now in principle be accessed over the Internet. Of paramount importance in the health domain is the need for the security and privacy of data that is transmitted across these networks. One such collaboration, which spans several specialist centres across France, Germany, Italy and the UK, is ENSAT - the European Network for the Study of Adrenal Tumors. The rarity of the tumors under study means the value of accessing, aggregating and comparing data from many centres is great indeed. However this is especially challenging given that ENSAT require clinical and genomic data to be seamlessly linked, but in such a way that the information governance, ethics and privacy concerns of the patients and associated stakeholders involved are visibly satisfied. Key to this is the clear separation of clinical and genomic data sets and support for rigorous patient-identity protecting access control. This is especially challenging when such data sets exist across different organisational boundaries. In this paper we describe a prototype solution offering a security-oriented tailored portal supported by a layered encryption-driven linkage technology (VANGUARD) that offers precisely such patient-privacy protecting capabilities. We describe the architecture, implementation and use to date of this facility to support the ENSAT adrenal cancer research network.

The ability to predict adverse hypotensive events, where a patient's arterial blood pressure drops to abnormally low (and dangerous) levels, would be of major benefit to the fields of primary and secondary health care, and especially to the traumatic brain injury domain. A wealth of data exist in health care systems providing information on the major health indicators of patients in hospitals (blood pressure, temperature, heart rate, etc.). It is believed that if enough of these data could be drawn together and analysed in a systematic way, then a system could be built that will trigger an alarm predicting the onset of a hypotensive event over a useful time scale, e.g. half an hour in advance. In such circumstances, avoidance measures can be taken to prevent such events arising. This is the basis for the Avert-IT project (http://www.avert-it.org), a collaborative EU-funded project involving the construction of a hypotension alarm system exploiting Bayesian neural networks using techniques of data federation to bring together the relevant information for study and system development.

The progressive scaling of complementary metal oxide semiconductor (CMOS) transistors drives the success of the global semiconductor industry. Detailed knowledge of transistor behaviour is necessary to overcome the many fundamental challenges faced by chip and systems designers. Grid technology has enabled the unavoidable statistical variations introduced by scaling to be examined in unprecedented detail. Over 200 000 transistors have been simulated, the results of which provide detailed insight into underlying physical processes. This paper outlines recent scientific results of the nanoCMOS project and describes the way in which the scientific goals have been reflected in the grid-based e-Infrastructure.

The simulation of biochemical networks provides insight and understanding about the underlying biochemical processes and pathways used by cells and organisms. BioNessie is a biochemical network simulator which has been developed at the University of Glasgow. This paper describes the simulator and focuses in particular on how it has been extended to benefit from a wide variety of high performance compute resources across the UK through Grid technologies to support larger scale simulations.

The paper documents a series of data integration workshops held in 2006 at the UK National e-Science Centre, summarizing a range of the problem/solution scenarios in multi-site and multi-scale data integration with six HealthGrid projects using schizophrenia as a domain-specific test case. It outlines emerging strategies, recommendations and objectives for collaboration on shared ontology-building and harmonization of data for multi-site trials in this domain.

Microarray experiments are one of the key ways in which gene activity can be identified and measured thereby shedding light and understanding for example on biological processes. The BBSRC funded Grid enabled Microarray Expression Profile Search (GEMEPS) project has developed an infrastructure which allows post-genomic life science researchers to ask and answer the following questions: who has undertaken microarray experiments that are in some way similar or relevant to mine; and how similar were these relevant experiments? Given that microarray experiments are expensive to undertake and may possess crucial information for future exploitation (both academically and commercially), scientists are wary of allowing unrestricted access to their data by the wider community until fully exploited locally. A key requirement is thus to have fine grained security that is easy to establish and simple (or ideally transparent) to use across inter-institutional virtual organisations. In this paper we present an enhanced security-oriented data Grid infrastructure that supports the definition of these kinds of queries and the analysis and comparison of microarray experiment results.