Planar waveguide biosensors for nucleic acid hybridization reactions

Journal ArticleOligonucleotide probes derived from (1) the T3 RNA polymerase promoter sequence (T3) and (2) prostate-specific antigen messenger RNA (PSA) were prepared and labeled with a red-emitting fluorescent dye (Cy5). The complimentary oligonucleotides (anti T3 and anti PSA) were prepared and labeled with biotin. Initially, a feasibility study was performed in which the hybridization rate of the T3/anti T3 oligonucleotide pair was examined. Specifically, biotinylated anti T3 was immobilized to a neutravidin-coated waveguide and solutions containing increasing concentrations of Cy5-labeled T3 were injected into the biosensor. Fluorescence emission was detected with an evanescent wave imaging fluorometer. The hybridization reaction proceeded rapidly with a significant amount of binding occurring during the first 5 minutes. A Michaelis-Menton kinetics model was used to analyze hybridization rate data and gave values of 78 nanomolar for the apparent affinity of the hybridization reaction and 1.4 picomolar for the analytical sensitivity of the hybridization assay. In subsequent studies the hybridization rate of the PSA/anti PSA oligonucleotide pair was examined. Biotinylated anti PSA was immobilized to the waveguide and solutions containing increasing concentrations of Cy5-labeled PSA were injected into the biosensor. The hybridization rate observed for formation of the PSA/anti PSA pair was comparable to the high rates observed for the T3/anti T3 pair. Lastly, the selectivity of the biosensor was examined using an oligonucleotide probe derived from human glandular kallikrein (hGK), which exhibits a high degree of homology to PSA. The two oligonucleotide probes (PSA and hGK) only differed in 7 out of 20 positions. Interestingly, the hybridization rate observed for Cy5-Iabeled hGK was very low-not statistically different from the non-specific binding rate of the hybridization assay

Boundary work during COVID-19: The transformation of research review and set-up

Background and aims: The rapid setting up of research during the COVID-19 pandemic led to changes in ways of working within research organisations. The aim of this study was to examine the experiences of staff involved in the research review and set-up system at a large NHS and university partnership in the UK through the lens of boundary theory. / Methods: We carried out a rapid qualitative appraisal based on telephone interviews (n=25) to explore how staff experienced the research review and set-up system during the pandemic. / Results: In light of the pressures created by the pandemic, the boundaries established to set up distinct groups and responsibilities were modified to allow for different ways of working. Some of the new structures and processes were seen positively and brought groups that previously worked at a distance closer together. / Conclusions: The reconceptualisation of relations within the research system during the pandemic added more fluidity to ways of working within the research office and contributed to closer working interactions and an expanded team ethos

Advancing the digital and computational capabilities of healthcare providers: A qualitative study of a hospital organisation in the NHS

Objective: Healthcare systems require transformation to meet societal challenges and projected health demands. Digital and computational tools and approaches are fundamental to this transformation, and hospitals have a key role to play in their development and implementation. This paper reports on a study with the objective of exploring the challenges encountered by hospital leaders and innovators as they implement a strategy to become a data-driven hospital organisation. In doing so, this paper provides guidance to future leaders and innovators seeking to build computational and digital capabilities in complex clinical settings. Methods: Interviews were undertaken with 42 participants associated with a large public hospital organisation within England's National Health Service. Using the concept of institutional readiness as an analytical framework, the paper explores participants’ perspectives on the organisation's capacity to support the development of, and benefit from, digital and computational approaches. Results: Participants’ accounts reveal a range of specific institutional readiness criteria relating to organisational vision, technical capability, organisational agility, and talent and skills that, when met, enhance the organisations’ capacity to support the development and implementation of digital and computational tools. Participant accounts also reveal challenges relating to these criteria, such as unrealistic expectations and the necessary prioritisation of clinical work in resource-constrained settings. Conclusions: The paper identifies a general set of institutional readiness criteria that can guide future hospital leaders and innovators aiming to improve their organisation's digital and computational capability. The paper also illustrates the challenges of pursuing digital and computational innovation in resource-constrained hospital environments

Redefining the research hospital

Introduction All medicine was innovation, once. Yet the contemporary notion of medical research is remarkably narrow. While every clinician is encouraged to be aware of the latest advances, only a few are expected to contribute to them. Anyone may be a patient, yet clinical practice is determined by the minority included in research studies. The aim of medicine is to improve the lives of patients, yet knowledge of disease is arbitrarily prioritised as its primary means. The agents of medicine are clinicians, yet new interventions are mostly created by others, within corporate enterprise deliberately kept at arm’s length. We treat the specific, individual patient in front of us, now, yet most research is addressed to faceless, generic groups, to be realised deep into an ill-defined, hypothetical future

Polarization Gradient Study of Interstellar Medium Turbulence Using The Canadian Galactic Plane Survey

We have investigated the magneto-ionic turbulence in the interstellar medium through spatial gradients of the complex radio polarization vector in the Canadian Galactic Plane Survey (CGPS). The CGPS data cover 1300 square-degrees, over the range ${53^{\circ}}\leq{\ell}\leq{192^{\circ}}$, ${-3^{\circ}}\leq{b}\leq{5^{\circ}}$ with an extension to ${b}={17.5^{\circ}}$ in the range ${101^{\circ}}\leq{\ell}\leq{116^{\circ}}$, and arcminute resolution at 1420 MHz. Previous studies found a correlation between the skewness and kurtosis of the polarization gradient and the Mach number of the turbulence, or assumed this correlation to deduce the Mach number of an observed turbulent region. We present polarization gradient images of the entire CGPS dataset, and analyze the dependence of these images on angular resolution. The polarization gradients are filamentary, and the length of these filaments is largest towards the Galactic anti-center, and smallest towards the inner Galaxy. This may imply that small-scale turbulence is stronger in the inner Galaxy, or that we observe more distant features at low Galactic longitudes. For every resolution studied, the skewness of the polarization gradient is influenced by the edges of bright polarization gradient regions, which are not related to the turbulence revealed by the polarization gradients. We also find that the skewness of the polarization gradient is sensitive to the size of the box used to calculate the skewness, but insensitive to Galactic longitude, implying that the skewness only probes the number and magnitude of the inhomogeneities within the box. We conclude that the skewness and kurtosis of the polarization gradient are not ideal statistics for probing natural magneto-ionic turbulence.Comment: 21 pages, 15 figures, accepted by Ap

Advanced Diagnostics for the Study of Linearly Polarized Emission. II: Application to Diffuse Interstellar Radio Synchrotron Emission

Diagnostics of polarized emission provide us with valuable information on the Galactic magnetic field and the state of turbulence in the interstellar medium, which cannot be obtained from synchrotron intensity alone. In Paper I (Herron et al. 2017b), we derived polarization diagnostics that are rotationally and translationally invariant in the $Q$-$U$ plane, similar to the polarization gradient. In this paper, we apply these diagnostics to simulations of ideal magnetohydrodynamic turbulence that have a range of sonic and Alfv\'enic Mach numbers. We generate synthetic images of Stokes $Q$ and $U$ for these simulations, for the cases where the turbulence is illuminated from behind by uniform polarized emission, and where the polarized emission originates from within the turbulent volume. From these simulated images we calculate the polarization diagnostics derived in Paper I, for different lines of sight relative to the mean magnetic field, and for a range of frequencies. For all of our simulations, we find that the polarization gradient is very similar to the generalized polarization gradient, and that both trace spatial variations in the magnetoionic medium for the case where emission originates within the turbulent volume, provided that the medium is not supersonic. We propose a method for distinguishing the cases of emission coming from behind or within a turbulent, Faraday rotating medium, and a method to partly map the rotation measure of the observed region. We also speculate on statistics of these diagnostics that may allow us to constrain the physical properties of an observed turbulent region.Comment: 34 pages, 25 figures, accepted for publication in Ap

The Value of Data: Applying a Public Value Model to the English National Health Service

Research and innovation in biomedicine and health care increasingly depend on electronic data. The emergence of data-driven technologies and associated digital transformations has focused attention on the value of such data. Despite the broad consensus of the value of health data, there is less consensus on the basis for that value; thus, the nature and extent of health data value remain unclear. Much of the existing literature presupposes that the value of data is to be understood primarily in financial terms, and assumes that a single financial value can be assigned. We here argue that the value of a dataset is instead relational; that is, the value depends on who wants to use it and for what purposes. Moreover, data are valued for both nonfinancial and financial reasons. Thus, it may be more accurate to discuss the values (plural) of a dataset rather than the singular value. This plurality of values opens up an important set of questions about how health data should be valued for the purposes of public policy. We argue that public value models provide a useful approach in this regard. According to public value theory, public value is created, or captured, to the extent that public sector institutions further their democratically established goals, and their impact on improving the lives of citizens. This article outlines how adopting such an approach might be operationalized within existing health care systems such as the English National Health Service, with particular focus on actionable conclusions