Structural development of the Devono-Carboniferous plays of the UK North Sea

Decades of oil and gas exploration across the North Sea have led to a detailed understanding of its Cenozoic–Mesozoic structure. However, the deeper basin architecture of Paleozoic petroleum systems has been less well defined by seismic data. This regional structural overview of the Devono-Carboniferous petroleum systems incorporates interpretations from more than 85 000 line-kilometres of 2D seismic data and 50 3D seismic volumes, plus a gravity, density and magnetic study, from the Central Silverpit Basin to the East Orkney Basin. A complex picture of previously unmapped or poorly known basins emerges on an inherited basement fabric, with numerous granite-cored blocks. These basins are controlled by Devono- Carboniferous normal, strike-slip and reverse faults. The main basins across Quadrants 29–44 trend NW–SE, influenced by the Tornquist trend inherited from the Caledonian basement. North of Quadrants 27 and 28, and the presumed Iapetus suture, the major depocentres are NE–SW (e.g. the Forth Approaches and Inner Moray Firth basins) to east–west (e.g. the Caithness Graben), and WNW–ESE trending (e.g. the East Orkney Basin), reflecting the basement structural inheritance. From seismic interpretation, there are indications of an older north–south fault trend in the Inner Moray Firth that is difficult to image, since it has been dissected by subsequent Permo-Carboniferous and Mesozoic faulting and rifting

Tectonic significance of changes in post-subduction Pliocene-Quaternary magmatism in the south east part of the Carpathian-Pannonian Region

The south-eastern part of the Carpathian–Pannonian region records the cessation of convergence between the European platform/Moesia and the Tisza–Dacia microplate. Plio-Quaternary magmatic activity in this area, in close proximity to the ‘Vrancea zone’, shows a shift from normal calc-alkaline to much more diverse compositions (adakite-like calc-alkaline, K-alkalic, mafic Na-alkalic and ultrapotassic), suggesting a significant change in geodynamic processes at approximately 3 Ma. We review the tectonic setting, timing, petrology and geochemistry of the post-collisional volcanism to constrain the role of orogenic building processes such as subduction or collision on melt production and migration. The calc-alkaline volcanism (5.3–3.9 Ma) marks the end of normal subduction-related magmatism along the post-collisional Călimani–Gurghiu–Harghita volcanic chain in front of the European convergent plate margin. At ca. 3 Ma in South Harghita magma compositions changed to adakite-like calc-alkaline and continued until recent times (< 0.03 Ma) interrupted at 1.6–1.2 Ma by generation of Na and K-alkalic magmas, signifying changes in the source and melting mechanism. We attribute the changes in magma composition in front of the Moesian platform to two main geodynamic events: (1) slab-pull and steepening with opening of a tear window (adakite-like calc-alkaline magmas) and (2) renewed contraction associated with deep mantle processes such as slab steepening during post-collisional times (Na and K-alkalic magmas). Contemporaneous post-collisional volcanism at the eastern edge of the Pannonian Basin at 2.6–1.3 Ma was dominated by Na-alkalic and ultrapotassic magmas, suggesting a close relationship with thermal asthenospheric doming and strain partitioning related to the Adriatic indentation. Similar timing, magma chamber processes and volume for K-alkalic (shoshonitic) magmas in the South Apuseni Mountains (1.6 Ma) and South Harghita area at a distance of ca. 200 km imply a regional connection with the inversion tectonics

Survival and disease characteristics of de novo versus recurrent metastatic breast cancer in a cohort of young patients

Abstract: Background: It is not clear how the pathology, presentation and outcome for patients who present with de novo metastatic breast cancer (dnMBC) compare with those who later develop distant metastases. DnMBC is uncommon in younger patients. We describe these differences within a cohort of young patients in the United Kingdom. Methods: Women aged 40 years or younger with a first invasive breast cancer were recruited to the prospective POSH national cohort study. Baseline clinicopathological data were collected, with annual follow-up. Overall survival (OS) and post-distant relapse-free survival (PDRS) were assessed using Kaplan–Meier curves. Results: In total, 862 patients were diagnosed with metastatic disease. DnMBC prevalence was 2.6% (76/2977). Of those with initially localised disease, 27.1% (786/2901) subsequently developed a distant recurrence. Median follow-up was 11.00 years (95% CI 10.79–11.59). Patients who developed metastatic disease within 12 months had worse OS than dnMBC patients (HR 2.64; 1.84–3.77). For PDRS, dnMBC was better than all groups, including those who relapsed after 5 years. Of dnMBC patients, 1.3% had a gBRCA1, and 11.8% a gBRCA2 mutation. Conclusions: Young women with dnMBC have better PDRS than those who develop relapsed metastatic breast cancer. A gBRCA2 mutation was overrepresented in dnMBC

Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer.

BACKGROUND: Substantial evidence supports an association between use of menopausal hormone therapy and decreased colorectal cancer (CRC) risk, indicating a role of exogenous sex hormones in CRC development. However, findings on endogenous oestrogen exposure and CRC are inconsistent. METHODS: We used a Mendelian randomisation approach to test for a causal effect of age at menarche and age at menopause as surrogates for endogenous oestrogen exposure on CRC risk. Weighted genetic risk scores based on 358 single-nucleotide polymorphisms associated with age at menarche and 51 single-nucleotide polymorphisms associated with age at menopause were used to estimate the association with CRC risk using logistic regression in 12,944 women diagnosed with CRC and 10,741 women without CRC from three consortia. Sensitivity analyses were conducted to address pleiotropy and possible confounding by body mass index. RESULTS: Genetic risk scores for age at menarche (odds ratio per year 0.98, 95% confidence interval: 0.95-1.02) and age at menopause (odds ratio 0.98, 95% confidence interval: 0.94-1.01) were not significantly associated with CRC risk. The sensitivity analyses yielded similar results. CONCLUSIONS: Our study does not support a causal relationship between genetic risk scores for age at menarche and age at menopause and CRC risk

Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer.

Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n = 169) and whole blood (n = 922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR ≤ 0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P = 2.2 × 10- 4, replication P = 0.01), and PYGL (discovery P = 2.3 × 10- 4, replication P = 6.7 × 10- 4). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P < 0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. This study is the first to implement PrediXcan in a large colorectal cancer study and findings highlight the utility of integrating transcriptome data in GWAS for discovery of, and biological insight into, risk loci

Strain rate effects on the tensile properties of a highly orientated thermoplastic composite material – elasticity and strength

This presentation looks at strain rate effects on the tensile properties of a highly orientated thermoplastic composite material – elasticity and strength

Strain rate effects on the shear properties of a highly orientated thermoplastic composite material using a non contacting extensometry method – elasticity and strength

This presentation looks at strain rate effects on the shear properties of a highly orientated thermoplastic composite material using a non contacting extensometry method – elasticity and strengt

Strain rate effects on the shear properties of a highly orientated thermoplastic composite material using a contacting displacement measurement methodology – Part B: Damage evolution

This paper is concerned with the characterisation of the shear mechanical properties of glass-fibre-reinforced thermoplastic composite laminates over a range of strain rates. The research was carried out as part of the DTI/EPSRC-funded CRACTAC programme, which was part of the FASMAT Foresight Vehicle suite of projects. Twenty-two [±45]2s laid-up specimens each were tested at 5, 50 and 500 (mm/min) crosshead displacement rates, using a universal testing machine. The longitudinal and transverse strains were obtained experimentally using contacting extensometry apparatus and then transformed to the ply axis using Classical Laminate Theory. A rigourous statistical treatment method was proposed for the processing and analysis of the raw data. The shear modulus decreased for increasing strain rate. The shear failure stress increased for increasing strain rate. Semi-empirical linear functions of the shear modulus and shear failure strength were proposed with respect to the logarithm of the shear strain rate. The shear failure strain was independent of strain rate. Finally, the observed opposing trends of in-plane shear modulus and shear failure stress suggested that shear damage evolution is strain rate dependent for the examined material

Strain rate effects on the shear properties of a thermoplastic composite laminate system using a contacting extensometry method

This presentation looks at strain rate effects on the shear properties of a thermoplastic composite laminate system using a contacting extensometry method

Risks of second non-breast primaries following breast cancer in women: a systematic review and meta-analysis

Background: second primary cancer incidence is rising among breast cancer survivors. We examined the risks of non-breast second primaries, in combination and at specific cancer sites, through a systematic review and meta-analysis. Methods: we conducted a systematic search of PubMed, Embase, and Web of Science, seeking studies published by March 2022. We included studies that reported standardized incidence ratios (SIRs), with associated standard errors, assessing the combined risk of second non-breast primaries following breast cancer. We performed meta-analyses of combined second primary risks, stratifying by age, follow-up duration, and geographic region. We also assessed second primary risks at several specific sites, stratifying by age. The inverse variance method with DerSimonian–Laird estimators was used in all meta-analyses, assuming a random-effects model. Associated biases and study quality were evaluated using the Newcastle–Ottawa scale. Results: one prospective and twenty-seven retrospective cohort studies were identified. SIRs for second non-breast primaries combined ranged from 0.84 to 1.84. The summary SIR estimate was 1.24 (95% CI 1.14–1.36, I 2: 99%). This varied by age: the estimate was 1.59 (95% CI 1.36–1.85) when breast cancer was diagnosed before age 50, which was significantly higher than in women first diagnosed at 50 or over (SIR: 1.13, 95% CI 1.01–1.36, p for difference: &lt; 0.001). SPC risks were also significantly higher when based on Asian, rather than European, registries (Asia—SIR: 1.47, 95% CI 1.29–1.67. Europe—SIR: 1.16, 95% CI 1.04–1.28). There were significantly increased risks of second thyroid (SIR: 1.89, 95% CI 1.49–2.38), corpus uteri (SIR: 1.84, 95% CI 1.53–2.23), ovary (SIR: 1.53, 95% CI 1.35–1.73), kidney (SIR: 1.43, 95% CI 1.17–1.73), oesophagus (SIR: 1.39, 95% CI 1.26–1.55), skin (melanoma) (SIR: 1.34, 95% CI 1.18–1.52), blood (leukaemia) (SIR: 1.30, 95% CI 1.17–1.45), lung (SIR: 1.25, 95% CI 1.03–1.51), stomach (SIR: 1.23, 95% CI 1.12–1.36) and bladder (SIR: 1.15, 95% CI 1.05–1.26) primaries. Conclusions: breast cancer survivors are at significantly increased risk of second primaries at many sites. Risks are higher for those diagnosed with breast cancer before age 50 and in Asian breast cancer survivors compared to European breast cancer survivors. This study is limited by a lack of data on potentially confounding variables. The conclusions may inform clinical management decisions following breast cancer, although specific clinical recommendations lie outside the scope of this review. </p