Biomedical optical sensing using nano-/micro-structured metamaterials

Work on optical sensing techniques continues to advance - and optical sensing techniques and related technologies are becoming a well-established approach for, inter alia, applications in biomedical and environmental sensing. Both structured surfaces and arrays of integrated devices that are fabricated by means of classical planar technologies are likely to have a central role in the development of low-cost and reliable biosensors, at both the molecular and cell levels. One approach that has been demonstrated as viable in biomedical sensing is the use of fluorescent labelling, e.g. for carrying out competition immunoassays to identify the possible presence of specific analyte molecules in suitably prepared fluid samples. Many bio-materials exhibit a finite level of fluorescence that could possibly be exploited in sensing, but is also potentially problematic when it forms an undesired background, thereby limiting sensitivity. But the alternative approach of label-free biomedical sensing seems likely to be favoured in future applications. A 'standard' approach to label-free sensing exploits the detection of changes in the (complex) refractive index that occur when bio-material is added to the local environment of a designed resonant structure, thereby changing its resonance frequency. Designed tuning of reflection, transmission and absorption resonances can be used to help identify specific molecules, through selection of the known bond resonances of the molecules of interest. Since it is typically possible to organise resonant structures in arrays that consist of thousands of individual resonant 'atoms', thereby forming a metasurface, it has become possible to select and quantify various characteristic molecular bond resonances simultaneously - and to identify possible molecular compositions in composite bio-material

The Flow Country: The peatlands of Caithness and Sutherland

This NCC publication is one of two which describes the nature conservation interest and importance of the Flow Country, in Caithness and Sutherland, northern Scotland. This area is now recognised as the largest expanse of blanket bog in Europe and the report provided the first global review of the extent of this peatland type. The Flow Country is of outstanding importance, both nationally and internationally. These peatlands are three times larger than any other in either Britain or Ireland. The scale and diversity of the habitat is unique, and the total size and range of bird species present, and other aspects of the fauna, is of international importance. At the time of publication, in the mid-1980s, this area was suffering from widespread afforestation. This 1988 review summarised NCC’s detailed surveys of peatland vegetation in the Flow Country, and is complementary to a 1987 publication Birds, bogs and forestry: the peatlands of Caithness and Sutherland which outlined the ornithological importance of this area, and documented and called for a halt to the destructive afforestation which was then occurring

Evaluating Baculovirus as a Vector for Human Prostate Cancer Gene Therapy

Gene therapy represents an attractive strategy for the non-invasive treatment of prostate cancer, where current clinical interventions show limited efficacy. Here, we evaluate the use of the insect virus, baculovirus (BV), as a novel vector for human prostate cancer gene therapy. Since prostate tumours represent a heterogeneous environment, a therapeutic approach that achieves long-term regression must be capable of targeting multiple transformed cell populations. Furthermore, discrimination in the targeting of malignant compared to non-malignant cells would have value in minimising side effects. We employed a number of prostate cancer models to analyse the potential for BV to achieve these goals. In vitro, both traditional prostate cell lines as well as primary epithelial or stromal cells derived from patient prostate biopsies, in two- or three-dimensional cultures, were used. We also evaluated BV in vivo in murine prostate cancer xenograft models. BV was capable of preferentially transducing invasive malignant prostate cancer cell lines compared to early stage cancers and non-malignant samples, a restriction that was not a function of nuclear import. Of more clinical relevance, primary patient-derived prostate cancer cells were also efficiently transduced by BV, with robust rates observed in epithelial cells of basal phenotype, which expressed BV-encoded transgenes faster than epithelial cells of a more differentiated, luminal phenotype. Maximum transduction capacity was observed in stromal cells. BV was able to penetrate through three-dimensional structures, including in vitro spheroids and in vivo orthotopic xenografts. BV vectors containing a nitroreductase transgene in a gene-directed enzyme pro-drug therapy approach were capable of efficiently killing malignant prostate targets following administration of the pro-drug, CB1954. Thus, BV is capable of transducing a large proportion of prostate cell types within a heterogeneous 3-D prostate tumour, can facilitate cell death using a pro-drug approach, and shows promise as a vector for the treatment of prostate cancer

Impact of COVID-19 on gestational diabetes pregnancy outcomes in the UK: A multicentre retrospective cohort study

Objective To determine the impact of implementing emergency care pathway(s) for screening, diagnosing and managing women with gestational diabetes (GDM) during COVID-19. Design Retrospective multicentre cohort. Setting Nine National Health Service (NHS) Hospital Trusts/Health boards in England and Scotland. Population 4915 women with GDM pre-pandemic (1 April 2018 to 31 March 2020), and 3467 women with GDM during the pandemic (1 May 2020 to 31 March 2021). Methods We examined clinical outcomes for women with GDM prior to and during the pandemic following changes in screening methods, diagnostic testing, glucose thresholds and introduction of virtual care for monitoring of antenatal glycaemia. Main Outcome Measures Intervention at birth, perinatal mortality, large-for-gestational-age infants and neonatal unit admission. Results The new diagnostic criteria more often identified GDM women who were multiparous, had higher body mass index (BMI) and greater deprivation, and less frequently had previous GDM (all p < 0.05). During COVID, these women had no differences in the key outcome measures. Of the women, 3% were identified with pre-existing diabetes at antenatal booking. Where OGTT continued during COVID, but virtual care was introduced, outcomes were also similar pre- and during the pandemic. Conclusions Using HbA1c and fasting glucose identified a higher risk GDM population during the pandemic but this had minimal impact on pregnancy outcomes. The high prevalence of undiagnosed pre-existing diabetes suggests that women with GDM risk factors should be offered HbA1c screening in early pregnancy

The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance

In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.</p

The Physical Processes of CME/ICME Evolution

As observed in Thomson-scattered white light, coronal mass ejections (CMEs) are manifest as large-scale expulsions of plasma magnetically driven from the corona in the most energetic eruptions from the Sun. It remains a tantalizing mystery as to how these erupting magnetic fields evolve to form the complex structures we observe in the solar wind at Earth. Here, we strive to provide a fresh perspective on the post-eruption and interplanetary evolution of CMEs, focusing on the physical processes that define the many complex interactions of the ejected plasma with its surroundings as it departs the corona and propagates through the heliosphere. We summarize the ways CMEs and their interplanetary CMEs (ICMEs) are rotated, reconfigured, deformed, deflected, decelerated and disguised during their journey through the solar wind. This study then leads to consideration of how structures originating in coronal eruptions can be connected to their far removed interplanetary counterparts. Given that ICMEs are the drivers of most geomagnetic storms (and the sole driver of extreme storms), this work provides a guide to the processes that must be considered in making space weather forecasts from remote observations of the corona.Peer reviewe