Translation research: from accurate diagnosis to appropriate treatment

This review article focuses on the various aspects of translational research, where research on human subjects can ultimately enhance the diagnosis and treatment of future patients. While we will use specific examples relating to the asbestos related cancer mesothelioma, it should be stressed that the general approach outlined throughout this review is readily applicable to other diseases with an underlying molecular basis. Through the integration of molecular-based technologies, systematic tissue procurement and medical informatics, we now have the ability to identify clinically applicable "genotype"-"phenotype" associations across cohorts of patients that can rapidly be translated into useful diagnostic and treatment strategies. This review will touch on the various steps in the translational pipeline, and highlight some of the most essential elements as well as possible roadblocks that can impact success of the program. Critical issues with regard to Institutional Review Board (IRB) and Health Insurance Portability and Accountability Act (HIPAA) compliance, data standardization, sample procurement, quality control (QC), quality assurance (QA), data analysis, preclinical models and clinical trials are addressed. The various facets of the translational pipeline have been incorporated into a fully integrated computational system, appropriately named Dx2Tx. This system readily allows for the identification of new diagnostic tests, the discovery of biomarkers and drugable targets, and prediction of optimal treatments based upon the underlying molecular basis of the disease

Opening access to administrative data for evaluating public services: the case of the Justice Data Lab

As government administrative data sets are increasingly made available for new (non-administrative) purposes, there is a need to improve access to such resources for voluntary and community organizations, social enterprises and private businesses for statistical analysis and evaluation purposes. The Justice Data Lab set up by the Ministry of Justice in the UK presents an innovative case of how administrative data can be linked to other data held by organizations delivering public services. The establishment of a unit within a secure setting holding evaluation and statistical expertise has enabled providers of programmes aimed at reducing re-offending to obtain evidence on how the impact of their interventions differs from that of a matched comparison group. This article explores the development of the Justice Data Lab, the methodological and other challenges faced, and the experiences of user organizations. The article draws out implications for future development of Data Labs and the use of administrative data for the evaluation of public services

HST and Spitzer imaging of red and blue galaxies at z~2.5: A correlation between size and star formation activity from compact quiescent galaxies to extended star forming galaxies

We present HST NICMOS+ACS and Spitzer IRAC+MIPS observations of 41 galaxies at 2<z<3.5 in the FIRES MS1054 field with red and blue rest-frame optical colors. About half of the galaxies are very compact (effective radii r_e < 1 kpc) at rest-frame optical wavelengths, the others are extended (1< r_e < 10 kpc). For reference, 1 kpc corresponds to 0.12 arcsec at z=2.5 in the adopted cosmology. We separate actively star forming galaxies from quiescent galaxies by modeling their rest-frame UV-NIR SEDs. The star forming galaxies span the full range of sizes, while the quiescent galaxies all have r_e<2kpc. In the redshift range where MIPS 24 micron imaging is a sensitive probe of re-radiated dust emission (z<2.5), the 24 micron fluxes confirm that the light of the small quiescent galaxies is dominated by old stars, rather than dust-enshrouded star formation or AGN activity. The inferred surface mass densities and velocity dispersions for the quiescent galaxies are very high compared to those in local galaxies. The galaxies follow a Kormendy relation (between surface brightness and size) with approximately the same slope as locally, but shifted to brighter surface brightnesses, consistent with a mean stellar formation redshift of z_f~5. This paper demonstrates a direct relation between star formation activity and size at z~2.5, and the existence of a significant population of massive, extremely dense, old stellar systems without readily identifiable counterparts in the local universe.Comment: Accepted for publication in Ap

A Forward-Design Approach to Increase the Production of Poly-3-Hydroxybutyrate in Genetically Engineered Escherichia coli

Biopolymers, such as poly-3-hydroxybutyrate (P(3HB)) are produced as a carbon store in an array of organisms and exhibit characteristics which are similar to oil-derived plastics, yet have the added advantages of biodegradability and biocompatibility. Despite these advantages, P(3HB) production is currently more expensive than the production of oil-derived plastics, and therefore, more efficient P(3HB) production processes would be desirable. In this study, we describe the model-guided design and experimental validation of several engineered P(3HB) producing operons. In particular, we describe the characterization of a hybrid phaCAB operon that consists of a dual promoter (native and J23104) and RBS (native and B0034) design. P(3HB) production at 24 h was around six-fold higher in hybrid phaCAB engineered Escherichia coli in comparison to E. coli engineered with the native phaCAB operon from Ralstonia eutropha H16. Additionally, we describe the utilization of non-recyclable waste as a low-cost carbon source for the production of P(3HB)

Gender, foundation degrees and the knowledge economy

This article questions the concept of ‘education for employment’, which constructs a discourse of individual and societal benefit in a knowledge‐driven economy. Recent policy emphasis in the European Union promotes the expansion of higher education and short‐cycle vocational awards such as the intermediate two‐year Foundation Degree recently introduced into England and Wales. Studies of vocational education and training (VET) and the knowledge economy have focused largely on the governance of education and on the development and drift of policy. Many VET programmes have also been considered for their classed, raced and gendered take‐up and subsequent effect on employment. This article builds on both fields of study to engage with the finer cross‐analyses of gender, social class, poverty, race and citizenship. In its analysis of policy texts the article argues that in spite of a discourse of inclusivity, an expanded higher education system has generated new inequalities, deepening social stratification. Drawing on early analyses of national quantitative data sets, it identifies emerging gendered, classed and raced patterns and considers these in relation to occupationally and hierarchically stratified labour markets, both within and without the knowledge economy

Universal saturation of electron dephasing in three-dimensional disordered metals

We have systematically investigated the low-temperature electron dephasing times $\tau_\phi$ in more than 40 three-dimensional polycrystalline impure metals with distinct material characteristics. In all cases, a saturation of the dephasing time is observed below about a (few) degree(s) Kelvin, depending on samples. The value of the saturated dephasing time $\tau_0$ [$\equiv \tau_\phi (T \to 0 {\rm K})$] falls basically in the range 0.005 to 0.5 ns for all samples. Particularly, we find that $\tau_0$ scales with the electron diffusion constant $D$ as $\tau_0 \sim D^{- \alpha}$, with $\alpha$ close to or slightly larger than 1, for over two decades of $D$ from about 0.1 to 10 cm$^2$/s. Our observation suggests that the saturation behavior of $\tau_\phi$ is universal and intrinsic in three-dimensional polycrystalline impure metals. A complete theoretical explanation is not yet available.Comment: 4 pages, 3 eps figure