Jipu Jiang

Changes Over Time in Sex Assignment for Disorders of Sex Development

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.

Novel associations in disorders of sex development: Findings from the I-DSD registry

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.

Shibboleth-based Access to and Usage of Grid Resources

Security underpins grids and e-research. Without a robust, reliable and simple grid security infrastructure combined with commonly accepted security practices, large portions of the research community and wider industry will not engage. The predominant way in which security is currently addressed in the grid community is through public key infrastructures (PKI) based upon X.509 certificates to support authentication. Whilst PKIs address user identity issues, authentication does not provide fine grained control over what users are allowed to do on remote resources (authorization). In this paper we outline how we have successfully combined Shibboleth and advanced authorization technologies to provide simplified (from the user perspective) but fine grained security for access to and usage of grid resources. We demonstrate this approach through different security focused e-science projects being conducted at the National e-Science Centre (NeSC) at the University of Glasgow. We believe that this model is widely applicable and encourage the further uptake of e-science by non-IT specialists in the research communities

The European Disorder of Sex Development Registry: A Virtual Research Environment

Disorders of sex development (DSD) are a rare group of conditions which require further research. Effective research into understanding the aetiology, as well as long-term outcome of these rare conditions, requires multicentre collaboration often across national boundaries. The EU-funded EuroDSD programme (www.eurodsd.eu) is one such collaboration involving clinical centres and clinical and genetic experts across Europe. At the heart of the EuroDSD collaboration is a European DSD registry and a targeted virtual research environment (VRE) that supports the sharing of DSD data. Security, ethics and information governance are cornerstones of this infrastructure. This paper describes the infrastructure that has been developed, the inherent challenges in security, availability and dependability that must be overcome for the enterprise to succeed and provides a sample of the data that are stored in the registry along with a summary analysis of the current data sets.

Federating distributed clinical data for the prediction of adverse hypotensive events

The ability to predict adverse hypotensive events, where a patients 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.

Single sign-on and authorization for dynamic virtual organizations

This is a pre-print of an article whose final and definitive form has been published in International Federation for Information Processing

Tool Support for Security-Oriented Virtual Research Collaborations

Collaboration is at the heart of e-Science and e-Research more generally. Successful collaborations must address both the needs of the end user researchers and the providers that make resources available. Usability and security are two fundamental requirements that are demanded by many collaborations and both concerns must be considered from both the researcher and resource provider perspective. In this paper we outline tools and methods developed at the National e-Science Centre (NeSC) that provide users with seamless, secure access to distributed resources through security-oriented research environments, whilst also allowing resource providers to define and enforce their own local access and usage policies through intuitive user interfaces. We describe these tools and illustrate their application in the ESRC-funded Data Management through e-Social Science (DAMES) and the JISC-funded SeeGEO projects

User-oriented Security Supporting Inter-disciplinary Life Science Research across the Grid

Understanding potential genetic factors in disease or development of personalised e-Health solutions require scientists to access a multitude of data and compute resources across the Internet from functional genomics resources through to epidemiological studies. The Grid paradigm provides a compelling model whereby seamless access to these resources can be achieved. However, the acceptance of Grid technologies in this domain by researchers and resource owners must satisfy particular constraints from this community - two of the most critical of these constraints being advanced security and usability. In this paper we show how the Internet2 Shibboleth technology combined with advanced authorisation infrastructures can help address these constraints. We demonstrate the viability of this approach through a selection of case studies across the complete life science spectrum.

Security Oriented e-Infrastructures Supporting Neurological Research and Clinical Trials

The neurological and wider clinical domains stand to gain greatly from the vision of the grid in providing seamless yet secure access to distributed, heterogeneous computational resources and data sets. Whilst a wealth of clinical data exists within local, regional and national healthcare boundaries, access to and usage of these data sets demands that fine grained security is supported and subsequently enforced. This paper explores the security challenges of the e-health domain, focusing in particular on authorization. The context of these explorations is the MRC funded VOTES (Virtual Organisations for Trials and Epidemiological Studies) and the JISC funded GLASS (Glasgow early adoption of Shibboleth project) which are developing Grid infrastructures for clinical trials with case studies in the brain trauma domain

An assessment of the quality of the I-DSD and the I-CAH registries - international registries for rare conditions affecting sex development

BackgroundWith the proliferation of rare disease registries, there is a need for registries to undergo an assessment of their quality against agreed standards to ensure their long-term sustainability and acceptability.This study was performed to evaluate the I-DSD and I-CAH Registries and identify their strengths and weaknesses.MethodsThe design and operational aspects of the registries were evaluated against published quality indicators. Additional criteria included the level of activity, international acceptability of the registries and their use for research.ResultsThe design of the I-DSD and I-CAH Registries provides them with the ability to perform multiple studies and meet the standards for data elements, data sources and eligibility criteria. The registries follow the standards for data security, governance, ethical and legal issues, sustainability and communication of activities. The data have a high degree of validity, consistency and accuracy and the completeness is maximal for specific conditions such as androgen insensitivity syndrome and congenital adrenal hyperplasia. In terms of research output, the external validity is strong but the wide variety of cases needs further review. The internal validity of data was condition specific and highest for conditions such as congenital adrenal hyperplasia. The shift of the registry from a European registry to an international registry and the creation of a discrete but linked CAH registry increased the number of users and stakeholders as well as the international acceptability of both registries.ConclusionsThe I-DSD and I-CAH registries comply with the standards set by expert organisations. Recent modifications in their operation have allowed the registries to increase their user acceptability.