Security and privacy requirements for a multi-institutional cancer research data grid: an interview-based study

<p>Abstract</p> <p>Background</p> <p>Data protection is important for all information systems that deal with human-subjects data. Grid-based systems – such as the cancer Biomedical Informatics Grid (caBIG) – seek to develop new mechanisms to facilitate real-time federation of cancer-relevant data sources, including sources protected under a variety of regulatory laws, such as HIPAA and 21CFR11. These systems embody new models for data sharing, and hence pose new challenges to the regulatory community, and to those who would develop or adopt them. These challenges must be understood by both systems developers and system adopters. In this paper, we describe our work collecting policy statements, expectations, and requirements from regulatory decision makers at academic cancer centers in the United States. We use these statements to examine fundamental assumptions regarding data sharing using data federations and grid computing.</p> <p>Methods</p> <p>An interview-based study of key stakeholders from a sample of US cancer centers. Interviews were structured, and used an instrument that was developed for the purpose of this study. The instrument included a set of problem scenarios – difficult policy situations that were derived during a full-day discussion of potentially problematic issues by a set of project participants with diverse expertise. Each problem scenario included a set of open-ended questions that were designed to elucidate stakeholder opinions and concerns. Interviews were transcribed verbatim and used for both qualitative and quantitative analysis. For quantitative analysis, data was aggregated at the individual or institutional unit of analysis, depending on the specific interview question.</p> <p>Results</p> <p>Thirty-one (31) individuals at six cancer centers were contacted to participate. Twenty-four out of thirty-one (24/31) individuals responded to our request- yielding a total response rate of 77%. Respondents included IRB directors and policy-makers, privacy and security officers, directors of offices of research, information security officers and university legal counsel. Nineteen total interviews were conducted over a period of 16 weeks. Respondents provided answers for all four scenarios (a total of 87 questions). Results were grouped by broad themes, including among others: governance, legal and financial issues, partnership agreements, de-identification, institutional technical infrastructure for security and privacy protection, training, risk management, auditing, IRB issues, and patient/subject consent.</p> <p>Conclusion</p> <p>The findings suggest that with additional work, large scale federated sharing of data within a regulated environment is possible. A key challenge is developing suitable models for authentication and authorization practices within a federated environment. Authentication – the recognition and validation of a person's identity – is in fact a global property of such systems, while authorization – the permission to access data or resources – mimics data sharing agreements in being best served at a local level. Nine specific recommendations result from the work and are discussed in detail. These include: (1) the necessity to construct separate legal or corporate entities for governance of federated sharing initiatives on this scale; (2) consensus on the treatment of foreign and commercial partnerships; (3) the development of risk models and risk management processes; (4) development of technical infrastructure to support the credentialing process associated with research including human subjects; (5) exploring the feasibility of developing large-scale, federated honest broker approaches; (6) the development of suitable, federated identity provisioning processes to support federated authentication and authorization; (7) community development of requisite HIPAA and research ethics training modules by federation members; (8) the recognition of the need for central auditing requirements and authority, and; (9) use of two-protocol data exchange models where possible in the federation.</p

Successful treatment of Candida parapsilosis mural endocarditis with combined caspofungin and voriconazole

BACKGROUND: Fungal mural endocarditis is a rare entity in which the antemortem diagnosis is seldom made. Seven cases of mural endocarditis caused by Candida spp. have been collected from literature and six of these patients died after treatment with amphotericin B. CASE PRESENTATION: We report a case of mural endocarditis diagnosed by transesophageal echocardiogram and positive blood cultures to Candida parapsilosis. Because blood cultures continued to yield C. parapsilosis despite caspofungin monotherapy, treatment with voriconazole was added. CONCLUSION: This is the first description of successful treatment of C. parapsilosis mural endocarditis with caspofungin and voriconazole

Bird-Like Anatomy, Posture, and Behavior Revealed by an Early Jurassic Theropod Dinosaur Resting Trace

BACKGROUND: Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a well-preserved theropod trackway in a Lower Jurassic ( approximately 198 million-year-old) lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. CONCLUSIONS/SIGNIFICANCE: The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods

Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood

Staphylococcus aureus infection is a frequent cause of sepsis in humans, a disease associated with high mortality and without specific intervention. When suspended in human or animal plasma, staphylococci are known to agglutinate, however the bacterial factors responsible for agglutination and their possible contribution to disease pathogenesis have not yet been revealed. Using a mouse model for S. aureus sepsis, we report here that staphylococcal agglutination in blood was associated with a lethal outcome of this disease. Three secreted products of staphylococci - coagulase (Coa), von Willebrand factor binding protein (vWbp) and clumping factor (ClfA) – were required for agglutination. Coa and vWbp activate prothrombin to cleave fibrinogen, whereas ClfA allowed staphylococci to associate with the resulting fibrin cables. All three virulence genes promoted the formation of thromboembolic lesions in heart tissues. S. aureus agglutination could be disrupted and the lethal outcome of sepsis could be prevented by combining dabigatran-etexilate treatment, which blocked Coa and vWbp activity, with antibodies specific for ClfA. Together these results suggest that the combined administration of direct thrombin inhibitors and ClfA-antibodies that block S. aureus agglutination with fibrin may be useful for the prevention of staphylococcal sepsis in humans

Neurotrophic gene polymorphisms and response to psychological therapy

Therapygenetics, the study of genetic determinants of response to psychological therapies, is in its infancy. Here, we investigate whether single-nucleotide polymorphisms in nerve growth factor (NGF) (rs6330) and brain-derived neutrotrophic factor (BDNF) (rs6265) genes predict the response to cognitive behaviour therapy (CBT). Neurotrophic genes represent plausible candidate genes: they are implicated in synaptic plasticity, response to stress, and are widely expressed in brain areas involved in mood and cognition. Allelic variation at both loci has shown associations with anxiety-related phenotypes. A sample of 374 anxiety-disordered children with white European ancestry was recruited from clinics in Reading, UK, and in Sydney, Australia. Participants received manualised CBT treatment and DNA was collected from buccal cells using cheek swabs. Treatment response was assessed at post-treatment and follow-up time points. We report first evidence that children with one or more copies of the T allele of NGF rs6330 were significantly more likely to be free of their primary anxiety diagnosis at follow-up (OR=0.60 (0.42–0.85), P=0.005). These effects remained even when other clinically relevant covariates were accounted for (OR=0.62 (0.41–0.92), P=0.019). No significant associations were observed between BDNF rs6265 and response to psychological therapy. These findings demonstrate that knowledge of genetic markers has the potential to inform clinical treatment decisions for psychotherapeutic interventions

The Osteology of the Basal Archosauromorph Tasmaniosaurus triassicus from the Lower Triassic of Tasmania, Australia

Proterosuchidae are the most taxonomically diverse archosauromorph reptiles sampled in the immediate aftermath of the Permo-Triassic mass extinction and represent the earliest radiation of Archosauriformes (archosaurs and closely related species). Proterosuchids are potentially represented by approximately 15 nominal species collected from South Africa, China, Russia, Australia and India, but the taxonomic content of the group is currently in a state of flux because of the poor anatomic and systematic information available for several of its putative members. Here, the putative proterosuchid Tasmaniosaurus triassicus from the Lower Triassic of Hobart, Tasmania (Australia),is redescribed. The holotype and currently only known specimen includes cranial and postcranial remains and the revision of this material sheds new light on the anatomy of the animal, including new data on the cranial endocast. Several bones are re-identified or reinterpreted, contrasting with the descriptions of previous authors. The new information provided here shows that Tasmaniosaurus closely resembles the South African proterosuchid Proterosuchus, but it differed in the presence of, for example, a slightly downturned premaxilla, a shorter anterior process of maxilla, and a diamond-shaped anterior end of interclavicle. Previous claims for the presence of gut contents in the holotype of Tasmaniosaurus are considered ambiguous. The description of the cranial endocast of Tasmaniosaurus provides for the first time information about the anatomy of this region in proterosuchids. The cranial endocast preserves possibly part of the vomero-nasal (= Jacobson's) system laterally to the olfactory bulbs. Previous claims of the absence of the vomero-nasal organs in archosaurs, which is suggested by the extant phylogenetic bracket, are questioned because its absence in both clades of extant archosaurs seems to be directly related with the independent acquisition of a non-ground living mode of life