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  • Regional Exploration and Characterisation of CO 2 Storage Prospects in the Utsira-Skade Aquifer, North Viking Graben, North Sea

    Lloyd, C.; email: christopher.lloyd-2@manchester.ac.uk; Huuse, M.; Barrett, B. J.; Newton, A. M. W. (Frontiers Media S.A., 2021-10-04)
    Subsurface CO2 storage is considered a key element of reducing anthropogenic emissions in virtually all scenarios compatible with limiting global warming to 1.5°C. The Utsira-Skade Aquifer (Utsira, Eir and Skade Formations), northern North Sea, has been identified as a suitable reservoir. Although the overall storage capacity of the full aquifer has been estimated based on regional data, it is lacking an integrated assessment of containment and internal heterogeneity, to identify optimal areas for injection and for calculation of site-specific storage capacities. A high-resolution, broadband 3D seismic reflection dataset, full waveform inverted velocity data and 102 exploration wells are utilised to provide a catalogue of CO2 storage prospects in the northern Utsira-Skade Aquifer. This is achieved through: 1) definition of the aquifer’s spatial limits; 2) calculation of porosity distribution; 3) assessment of the extent, geomorphology, thickness variability, and containment confidence (CC) of mudstones; and 4) mapping of closures through fill-to-spill simulations. CO2 storage capacity was calculated for the prospects using two approaches; using the full reservoir thickness (FRT) beneath the closures and using only the thickness from the closure top to the spill point (TSP), i.e., within structural traps. Porosity ranges from 29 to 39% across the aquifer and is higher in the Utsira and Eir Fms. relative to the underlying Skade Fm. The mudstone separating the Skade and Eir/Utsira Fm. has a thickness > 50 m, and is a potential barrier for CO2. Other intra-aquifer mudstones were mainly interpreted to act as baffles to flow. Structural traps at the top Utsira and Skade Fms. yield fifteen prospects, with criteria of > 700 m depth and FRT storage capacity of > 5 Mt CO2. They have a combined storage capacity of 330 Mt CO2 (FRT) or 196 Mt CO2 (TSP). Five prospects have a positive CC score (total capacity: 54 Mt CO2 FRT or 39 Mt CO2 TSP). Additional storage capacity could be achieved through more detailed analysis of the seal to upgrade the CC scores, or through use of a network of the mapped closures with a fill-to-spill approach, utilising more of the aquifer.
  • Visual impairment and medication safety: a protocol for a scoping review.

    Giles, Sally J; orcid: 0000-0003-1623-6029; email: sally.giles@manchester.ac.uk; Panagioti, Maria; Riste, Lisa; Cheraghi-Sohi, Sudeh; Lewis, Penny; Adeyemi, Isabel; Davies, Karen; Morris, Rebecca; Phipps, Denham; Dickenson, Christine; et al. (2021-09-15)
    <h4>Background</h4>The number of individuals with a visual impairment in the UK was estimated a few years ago to be around 1.8 million. People can be visually impaired from birth, childhood, early adulthood or later in life. Those with visual impairment are subject to health inequities and increased risk for patient safety incidents in comparison to the general population. They are also known to be at an increased risk of experiencing medication errors compared to those without visual impairment. In view of this, this review aims to understand the issues of medication safety for VI people.<h4>Methods/design</h4>Four electronic bibliographic databases will be searched: MEDLINE, Embase, PsycInfo and CINAHL. Our search strategy will include search combinations of two key blocks of terms. Studies will not be excluded based on design. Included studies will be empirical studies. They will include studies that relate to both medication safety and visual impairment. Two reviewers (SG and LR) will screen all the titles and abstracts. SG, LR, RM, SCS and PL will perform study selection and data extraction using standard forms. Disagreements will be resolved through discussion or third party adjudication. Data to be collected will include study characteristics (year, objective, research method, setting, country), participant characteristics (number, age, gender, diagnoses), medication safety incident type and characteristics.<h4>Discussion</h4>The review will summarise the literature relating to medication safety and visual impairment.
  • Parental Licensing as Harm Reduction

    Shields, Liam; orcid: 0000-0001-9272-1937; email: liam.shields@manchester.ac.uk (Springer US, 2020-10-17)
    Abstract: In this paper, I will argue that some prominent objections to parental licensing rely on dubious claims about the existence of a very stringent, if not indefeasible, right to parent, which would be violated by licensing. I claim that attaching such stringency to the right only makes sense if we make a number of idealising assumptions. Otherwise, it is deeply implausible. Instead, I argue that we should evaluate parental licensing policies in much the same way we would harm reduction policies. By adopting this critical perspective, we can see that there are powerful, but quite different, reasons to be cautious about parental licensing relating to our ability to minimize the harmful effects of mass-parenting in a world of minimal surveillance and intervention.
  • Stress Corrosion Cracking of Additively Manufactured Alloy 625

    Cabrini, Marina; orcid: 0000-0003-3901-8657; email: marina.cabrini@unibg.it; Lorenzi, Sergio; orcid: 0000-0002-1337-7590; email: sergio.lorenzi@unibg.it; Testa, Cristian; orcid: 0000-0002-6064-9851; email: cristian.testa@guest.unibg.it; Carugo, Francesco; email: francesco.carugo@unibg.it; Pastore, Tommaso; orcid: 0000-0002-1443-7786; email: tommaso.pastore@unibg.it; Manfredi, Diego; orcid: 0000-0002-2876-143X; email: diego.manfredi@polito.it; Biamino, Sara; orcid: 0000-0003-1840-7717; email: sara.biamino@polito.it; Marchese, Giulio; orcid: 0000-0002-4637-5532; email: giulio.marchese@polito.it; Parizia, Simone; orcid: 0000-0002-1616-2800; email: simone.parizia@polito.it; Scenini, Fabio; orcid: 0000-0002-8974-4860; email: fabio.scenini@manchester.ac.uk (MDPI, 2021-10-15)
    Laser bed powder fusion (LPBF) is an additive manufacturing technology for the fabrication of semi-finished components directly from computer-aided design modelling, through melting and consolidation, layer upon layer, of a metallic powder, with a laser source. This manufacturing technique is particularly indicated for poor machinable alloys, such as Alloy 625. However, the unique microstructure generated could modify the resistance of the alloy to environment assisted cracking. The aim of this work was to analyze the stress corrosion cracking (SCC) and hydrogen embrittlement resistance behavior of Alloy 625 obtained by LPBF, both in as-built condition and after a standard heat treatment (grade 1). U-bend testing performed in boiling magnesium chloride at 155 and 170 °C confirmed the immunity of the alloy to SCC. However, slow strain rate tests in simulated ocean water on cathodically polarized specimens highlighted the possibility of the occurrence of hydrogen embrittlement in a specific range of strain rate and cathodic polarization. The very fine grain size and dislocation density of the thermally untreated specimens appeared to increase the hydrogen diffusion and embrittlement effect on pre-charged specimens that were deformed at the high strain rate. Conversely, heat treatment appeared to mitigate hydrogen embrittlement at high strain rates, however at the slow strain rate all the specimens showed a similar behavior.
  • Replication catastrophe is responsible for intrinsic PAR glycohydrolase inhibitor-sensitivity in patient-derived ovarian cancer models

    Coulson-Gilmer, Camilla; Morgan, Robert D.; Nelson, Louisa; Barnes, Bethany M.; Tighe, Anthony; Wardenaar, René; Spierings, Diana C. J.; Schlecht, Helene; Burghel, George J.; Foijer, Floris; et al. (BioMed Central, 2021-10-16)
    Abstract: Background: Patients with ovarian cancer often present at advanced stage and, following initial treatment success, develop recurrent drug-resistant disease. PARP inhibitors (PARPi) are yielding unprecedented survival benefits for women with BRCA-deficient disease. However, options remain limited for disease that is platinum-resistant and/or has inherent or acquired PARPi-resistance. PARG, the PAR glycohydrolase that counterbalances PARP activity, is an emerging target with potential to selectively kill tumour cells harbouring oncogene-induced DNA replication and metabolic vulnerabilities. Clinical development of PARG inhibitors (PARGi) will however require predictive biomarkers, in turn requiring an understanding of their mode of action. Furthermore, differential sensitivity to PARPi is key for expanding treatment options available for patients. Methods: A panel of 10 ovarian cancer cell lines and a living biobank of patient-derived ovarian cancer models (OCMs) were screened for PARGi-sensitivity using short- and long-term growth assays. PARGi-sensitivity was characterized using established markers for DNA replication stress, namely replication fibre asymmetry, RPA foci, KAP1 and Chk1 phosphorylation, and pan-nuclear γH2AX, indicating DNA replication catastrophe. Finally, gene expression in sensitive and resistant cells was also examined using NanoString or RNAseq. Results: PARGi sensitivity was identified in both ovarian cancer cell lines and patient-derived OCMs, with sensitivity accompanied by markers of persistent replication stress, and a pre-mitotic cell cycle block. Moreover, DNA replication genes are down-regulated in PARGi-sensitive cell lines consistent with an inherent DNA replication vulnerability. However, DNA replication gene expression did not predict PARGi-sensitivity in OCMs. The subset of patient-derived OCMs that are sensitive to single-agent PARG inhibition, includes models that are PARPi- and/or platinum-resistant, indicating that PARG inhibitors may represent an alternative treatment strategy for women with otherwise limited therapeutic options. Conclusions: We discover that a subset of ovarian cancers are intrinsically sensitive to pharmacological PARG blockade, including drug-resistant disease, underpinned by a common mechanism of replication catastrophe. We explore the use of a transcript-based biomarker, and provide insight into the design of future clinical trials of PARGi in patients with ovarian cancer. However, our results highlight the complexity of developing a predictive biomarker for PARGi sensitivity.

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