Detection of HTLV-1 proviral DNA in cell-free DNA: potential for non-invasive monitoring of Adult T cell leukaemia/lymphoma using liquid biopsy?

Introduction: Fragmented genomic DNA is constitutively released from dying cells into interstitial fluid in healthy tissue. In cancer, this so-called ‘cell-free’ DNA (cfDNA) released from dying malignant cells encodes cancer-associated mutations. Thus, minimally invasive sampling of cfDNA in blood plasma can be used to diagnose, characterise and longitudinally monitor solid tumours at remote sites in the body. ~5% of carriers of Human T cell leukaemia virus type 1 (HTLV-1) develop Adult T cell leukaemia/lymphoma (ATL), and a similar percentage develop an inflammatory CNS disease, HTLV-1 associated myelopathy (HAM). In both ATL and HAM, high frequencies of HTLV-1 infected cells are present in the affected tissue: each carrying an integrated DNA copy of the provirus. We hypothesised that turnover of infected cells results in the release of HTLV-1 proviruses in cfDNA, and that analysis of cfDNA from infected cells in HTLV-1 carriers might contain clinically useful information pertaining to inaccessible sites in the body- e.g. for early detection of primary or relapsing localised lymphoma type ATL. To evaluate the feasibility of this approach, we tested for HTLV-1 proviruses in blood plasma cfDNA. Methods: CfDNA (from blood plasma) and genomic DNA (gDNA, from peripheral blood mononuclear cells, PBMC) was isolated from blood from 6 uninfected controls, 24 asymptomatic carriers (AC), 21 patients with HAM and 25 patients with ATL. Proviral (HTLV-1 Tax) and human genomic DNA (the beta globin gene, HBB) targets were quantified by qPCR using primer pairs optimised for fragmented DNA. Results: Pure, high quality cfDNA was successfully extracted from blood plasma of all study participants. When compared with uninfected controls, HTLV-1 carriers had higher concentrations of cfDNA circulating in their blood plasma. Patients with ATL who were not in remission had the highest levels of blood plasma cfDNA in any group studied. HTLV-1 proviral DNA was detected in 60/70 samples obtained from HTLV-1 carriers. The proviral load (percentage of cells carrying proviruses) was approximately tenfold lower in plasma cfDNA than in PBMC genomic DNA, and there was a strong correlation between the proviral load in cfDNA and PBMC genomic DNA in HTLV-1 carriers that did not have ATL. cfDNA samples in which proviruses were undetectable also had very low proviral load in PBMC genomic DNA. Finally, detection of proviruses in cfDNA of patients with ATL was predictive of clinical status: patients with evolving disease had higher than expected total amount of proviruses detectable in plasma cfDNA. Discussion: We demonstrated that (1) HTLV-1 infection is associated with increased levels of blood plasma cfDNA, (2) proviral DNA is released into blood plasma cfDNA in HTLV-1 carriers and (3) proviral burden in cfDNA correlates with clinical status, raising the possibility of developing assays of cfDNA for clinical use in HTLV-1 carriers

The effect of the General Data Protection Regulation on medical research

Background: The enactment of the General Data Protection Regulation (GDPR) will impact on European data science. Particular concerns relating to consent requirements that would severely restrict medical data research have been raised. Objective: Our objective is to explain the changes in data protection laws that apply to medical research and to discuss their potential impact. Methods: Analysis of ethicolegal requirements imposed by the GDPR. Results: The GDPR makes the classification of pseudonymised data as personal data clearer, although it has not been entirely resolved. Biomedical research on personal data where consent has not been obtained must be of substantial public interest. Conclusions: The GDPR introduces protections for data subjects that aim for consistency across the EU. The proposed changes will make little impact on biomedical data research

Purely gravito-magnetic vacuum space-times

It is shown that there are no vacuum space-times (with or without cosmological constant) for which the Weyl-tensor is purely gravito-magnetic with respect to a normal and timelike congruence of observers.Comment: 4 page

Geometric Interpretation of the Mixed Invariants of the Riemann Spinor

Mixed invariants are used to classify the Riemann spinor in the case of Einstein-Maxwell fields and perfect fluids. In the Einstein-Maxwell case these mixed invariants provide information as to the relative orientation of the gravitational and electromagnetic principal null directions. Consideration of the perfect fluid case leads to some results about the behaviour of the Bel-Robinson tensor regarded as a quartic form on unit timelike vectors.Comment: 31 pages, AMS-LaTe

Space-times which are asymptotic to certain Friedman-Robertson-Walker space-times at timelike infinity

We define space-times which are asymptotic to radiation dominant Friedman-Robertson-Walker space-times at timelike infinity and study the asymptotic structure. We discuss the local asymptotic symmetry and give a definition of the total energy from the electric part of the Weyl tensor.Comment: 8 pages, Revte

Research Support in Australian Academic Libraries: Services, Resources, and Relationships

In the last decade Australian academic libraries have increasingly aligned their research support services with assessment criteria used in the national research evaluation exercise (Excellence for Research in Australia). The same period has seen growing interest in research impact outside of traditional measures, such as bibliometrics. Social media has provided opportunities for research dissemination and new tools, altmetrics, to measure these activities have emerged. This article reports on research into the extent and nature of research support services at Australian academic libraries, how the services are managed, and the factors that influence their development and delivery. Quantitative and qualitative research methods were used to compare the findings with an earlier study and to provide a deeper understanding of research support in Australia. Three key themes, services, staff and resourcing, and relationships, are discussed in relation to the management and challenges faced in providing research support

Aminophobanes:hydrolytic stability, tautomerism and application in Cr-catalysed ethene oligomerisation

The bicyclic aminophobanes have significantly different chemistry from their acyclic analogues Cy2PNHR′.</p

Ricci Collineations for type B warped space-times

We present the general structure of proper Ricci Collineations (RC) for type B warped space-times. Within this framework, we give a detailed description of the most general proper RC for spherically symmetric metrics. As examples, static spherically symmetric and Friedmann-Robertson-Walker space-times are considered.Comment: 18 pages, Latex, To appear in GR

Metrics to evaluate research performance in academic institutions: A critique of ERA 2010 as applied in forestry and the indirect H2 index as a possible alternative

Excellence for Research in Australia (ERA) is an attempt by the Australian Research Council to rate Australian universities on a 5-point scale within 180 Fields of Research using metrics and peer evaluation by an evaluation committee. Some of the bibliometric data contributing to this ranking suffer statistical issues associated with skewed distributions. Other data are standardised year-by-year, placing undue emphasis on the most recent publications which may not yet have reliable citation patterns. The bibliometric data offered to the evaluation committees is extensive, but lacks effective syntheses such as the h-index and its variants. The indirect H2 index is objective, can be computed automatically and efficiently, is resistant to manipulation, and a good indicator of impact to assist the ERA evaluation committees and to similar evaluations internationally.Comment: 19 pages, 6 figures, 7 tables, appendice