Guidance for researchers wanting to link NHS data using non-consent approaches: a thematic analysis of feedback from the Health Research Authority Confidentiality Advisory Group

Introduction: The use of linked data and non-consent methodologies is a rapidly growing area of health research due to the increasing detail, availability and scope of routinely collected electronic health records data. However, gaining the necessary legal and governance approvals to undertake data linkage is a complex process in England. / Objectives: We reflect on our own experience of establishing lawful basis for data linkage through Section 251 approval, with the intention to build a knowledgebase of practical advice for future applicants. / Methods: Thematic analysis was conducted on a corpus of Section 251 feedback reports from the NHS Health Research Authority Confidentiality Advisory Group. / Results: Four themes emerged from the feedback. These were: (a) Patient and Public Involvement, (b)~Establishing Rationale, (c) Data maintenance and contingency, and the need to gain (d) Further Permissions from external authorities prior to full approval. / Conclusions: Securing Section 251 approval poses ethical, practical and governance challenges. However, through a comprehensive, planned approach Section 251 approval is possible, enabling researchers to unlock the potential of linked data for the purposes of health research

Repurposing Albendazole: new potential as a chemotherapeutic agent with preferential activity against HPV-negative head and neck squamous cell cancer.

Albendazole is an anti-helminthic drug that has been shown to exhibit anti-cancer properties, however its activity in head and neck squamous cell cancer (HNSCC) was unknown. Using a series of in vitro assays, we assessed the ability of albendazole to inhibit proliferation in 20 HNSCC cell lines across a range of albendazole doses (1 nM-10 μM). Cell lines that responded to treatment were further examined for cell death, inhibition of migration and cell cycle arrest. Thirteen of fourteen human papillomavirus-negative HNSCC cell lines responded to albendazole, with an average IC50 of 152 nM. In contrast, only 3 of 6 human papillomavirus-positive HNSCC cell lines responded. Albendazole treatment resulted in apoptosis, inhibition of cell migration, cell cycle arrest in the G2/M phase and altered tubulin distribution. Normal control cells were not measurably affected by any dose tested. This study indicates that albendazole acts to inhibit the proliferation of human papillomavirus-negative HNSCC cell lines and thus warrants further study as a potential chemotherapeutic agent for patients suffering from head and neck cancer

Probing the low-luminosity GRB population with new generation satellite detectors

We compare the detection rates and redshift distributions of low-luminosity (LL) GRBs localized by Swift with those expected to be observed by the new generation satellite detectors on GLAST (now Fermi) and, in future, EXIST. Although the GLAST burst telescope will be less sensitive than Swift's in the 15--150 keV band, its large field-of-view implies that it will double Swift's detection rate of LL bursts. We show that Swift, GLAST and EXIST should detect about 1, 2 & 30 LL GRBs, respectively, over a 5-year operational period. The burst telescope on EXIST should detect LL GRBs at a rate of more than an order of magnitude greater than that of Swift's BAT. We show that the detection horizon for LL GRBs will be extended from $z \simeq 0.4$ for Swift to $z \simeq 1.1$ in the EXIST era. Also, the contribution of LL bursts to the observed GRB redshift distribution will contribute to an identifiable feature in the distribution at $z \simeq 1$.Comment: 6 pages, 4 figures, accepted by MNRA

A comparative study of MEA and DEA for post-combustion CO2 capture with different process configurations

This paper presented a comparative study of monoethanolamine (MEA) and diethanolamine (DEA) for post-combustion CO2 capture (PCC) process with different process configurations to study the interaction effect between solvent and process. The steady state process model of the conventional MEA-based PCC process was developed in Pro/II® and was validated with the experimental data. Then ten different process configurations were simulated for both MEA and DEA. Their performances in energy consumption were compared in terms of reboiler duty and total equivalent work. The results show that DEA generally has better thermal performances than MEA for all these ten process configurations. Seven process configurations provide 0.38%–4.61% total energy saving compared with the conventional PCC process for MEA, and other two configurations are not favourable. For DEA, except one configuration, other process configurations have 0.27%–4.50% total energy saving. This work also analyzed the sensitivities of three key parameters (amine concentration, stripper pressure and lean solvent loading) in conventional process and five process modifications to show optimization strategy

The stellar evolution of Luminous Red Galaxies, and its dependence on colour, redshift, luminosity and modelling

We present a series of colour evolution models for Luminous Red Galaxies (LRGs) in the 7th spectroscopic data release of the Sloan Digital Sky Survey (SDSS), computed using the full-spectrum fitting code VESPA on high signal-to-noise stacked spectra. The colour-evolution models are computed as a function of colour, luminosity and redshift, and we do not a-priori assume that LRGs constitute a uniform population of galaxies in terms of stellar evolution. By computing star-formation histories from the fossil record, the measured stellar evolution of the galaxies is decoupled from the survey's selection function, which also evolves with redshift. We present these evolutionary models computed using three different sets of Stellar Population Synthesis (SPS) codes. We show that the traditional fiducial model of purely passive stellar evolution of LRGs is broadly correct, but it is not sufficient to explain the full spectral signature. We also find that higher-order corrections to this model are dependent on the SPS used, particularly when calculating the amount of recent star formation. The amount of young stars can be non-negligible in some cases, and has important implications for the interpretation of the number density of LRGs within the selection box as a function of redshift. Dust extinction, however, is more robust to the SPS modelling: extinction increases with decreasing luminosity, increasing redshift, and increasing r-i colour. We are making the colour evolution tracks publicly available at http://www.icg.port.ac.uk/~tojeiror/lrg_evolution/.Comment: 29 pages, 34 figures, re-submitted to MNRAS after addressing the referee's repor

Mycobacterium abscessus and Children with Cystic Fibrosis

We prospectively studied 298 patients with cystic fibrosis (mean age 11.3 years; range 2 months to 32 years; sex ratio, 0.47) for nontuberculous mycobacteria in respiratory samples from January 1, 1996, to December 31, 1999. Mycobacterium abscessus was by far the most prevalent nontuberculous mycobacterium: 15 patients (6 male, 9 female; mean age 11.9 years; range 2.5–22 years) had at least one positive sample for this microorganism (versus 6 patients positive for M. avium complex), including 10 with >3 positive samples (versus 3 patients for M. avium complex). The M. abscessus isolates from 14 patients were typed by pulsed-field gel electrophoresis: each of the 14 patients harbored a unique strain, ruling out a common environmental reservoir or person-to-person transmission. Water samples collected in the cystic fibrosis center were negative for M. abscessus. This major mycobacterial pathogen in children and teenagers with cystic fibrosis does not appear to be acquired nosocomially

Addressing inequities in maternal health among women living in communities of social disadvantage and ethnic diversity.

The response to the coronavirus outbreak and how the disease and its societal consequences pose risks to already vulnerable groups such those who are socioeconomically disadvantaged and ethnic minority groups. Researchers and community groups analysed how the COVID-19 crisis has exacerbated persisting vulnerabilities, socio-economic and structural disadvantage and discrimination faced by many communities of social disadvantage and ethnic diversity, and discussed future strategies on how best to engage and involve local groups in research to improve outcomes for childbearing women experiencing mental illness and those living in areas of social disadvantage and ethnic diversity. Discussions centred around: access, engagement and quality of care; racism, discrimination and trust; the need for engagement with community stakeholders; and the impact of wider social and economic inequalities. Addressing biomedical factors alone is not sufficient, and integrative and holistic long-term public health strategies that address societal and structural racism and overall disadvantage in society are urgently needed to improve health disparities and can only be implemented in partnership with local communities

Fluid venting in the eastern Aleutian subduction zone

Fluid venting has been observed along 800 km of the Alaska convergent margin. The fluid venting sites are located near the deformation front, are controlled by subsurface structures, and exhibit the characteristics of cold seeps seen in other convergent margins. The more important characteristics include (1) methane plumes in the lower water column with maxima above the seafloor which are traceable to the initial deformation ridges; (2) prolific colonies of vent biota aligned and distributed in patches controlled by fault scarps, over‐steepened folds or outcrops of bedding planes; (3) calcium carbonate and barite precipitates at the surface and subsurface of vents; and (4) carbon isotope evidence from tissue and skeletal hard parts of biota, as well as from carbonate precipitates, that vents expel either methane‐ or sulfide‐dominated fluids. A biogeochemical approach toward estimating fluid flow rates from individual vents based on oxygen flux measurements and vent fluid analysis indicates a mean value of 5.5±0.7 L m−2 d−1 for tectonics‐induced water flow [Wallmann et al., 1997b]. A geophysical estimate of dewatering from the same area [von Huene et al., 1997] based on sediment porosity reduction shows a fluid loss of 0.02 L m−2 d−1 for a 5.5 km wide converged segment near the deformation front. Our video‐guided surveys have documented vent biota across a minimum of 0.1% of the area of the convergent segment off Kodiak Island; hence an average rate of 0.006 L m−2 d−1 is estimated from the biogeochemical approach. The two estimates for tectonics‐induced water flow from the accretionary prism are in surprisingly good agreement

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe