Digital: accelerating the pathway.

The Spherical Tokamak for Energy Production (STEP) programme is an ambitious but challenging endeavour to design and deliver a prototype fusion power plant. It is a rapid, fast-moving programme, designing a first of a kind device in a Volatile, Uncertain, Complex and Ambiguous (VUCA) environment, and digital tools play a pivotal role in managing and navigating this space. Digital helps manage the complexity and sheer volume of information. Advanced modelling and simulation techniques provide a platform for designers to explore various scenarios and iteratively refine designs, providing insights into the intricate interplay of requirements, constraints and design factors across physics, technology and engineering domains and aiding informed decision-making amidst uncertainties. It also provides a means of building confidence in the new scientific, technological and engineering solutions, given that a full-scale-integrated precursor test is not feasible, almost by definition. The digital strategy for STEP is built around a vision of a digital twin of the whole plant. This will evolve from the current digital shadow formed by system architecting codes and complex workflows and will be underpinned by developing capabilities in plasma, materials and engineering simulation, data management, advanced control, industrial cybersecurity, regulation, digital technologies and related digital disciplines. These capabilities will help address the key challenges of managing the complexity and quantity of information, improving the reliability and robustness of the current digital shadow and developing an understanding of its validity and performance.This article is part of the theme issue 'Delivering Fusion Energy - The Spherical Tokamak for Energy Production (STEP)'.

Combining MYD88 L265P mutation detection and clonality determination on CSF cellular and cell-free DNA improves diagnosis of primary CNS lymphoma.

Diagnosis of primary central nervous system lymphoma (PCNSL) is challenging, and although brain biopsy remains the gold standard, cerebrospinal fluid (CSF) constitutes a less invasive source of lymphomatous biomarkers. In a retrospective cohort of 54 PCNSL cases tested at diagnosis or relapse, we evaluated the contribution of immunoglobulin heavy chain (IGH) gene clonality and MYD88 L265P detection on both CSF cell pellets and supernatants, in comparison with cytology, flow cytometry, interleukin (IL)-10 and IL-6 quantification. Clonality assessment included a new assay to detect partial IGH-DJ rearrangements. Clonal IGH rearrangements and/or MYD88 L265P mutation were detected in 27 (50%) cell pellets and 24 (44%) supernatant cell-free (cf) DNA. Combining analyses on both compartments, 36 (66%) cases had at least one detectable molecular marker, present only in cfDNA for 9 (16%) of them. While cytology and flow cytometry were positive in only 7 (13.0%) and 9 (17.3%) cases respectively, high IL-10 levels were observed in 36 (66.7%) cases. Overall, taking into account molecular and cytokine results, 46/54 (85%) cases had at least one lymphomatous biomarker detectable in the CSF. These results show that this combination of biomarkers evaluated on both cell pellet and supernatant CSF fractions improves significantly the biological diagnosis of PCNSL.

Glutathione S-transferases related to P. aeruginosa lung infection in cystic fibrosis children: preliminary study.

OBJECTIVES: In cystic fibrosis (CF) children, we investigated the predictive impact of glutathione S-transferases (GST) activity and genotypes P1, M1 and T1, and antioxidant levels on stage-severity of Pseudomonas aeruginosa lung infection. METHODS: GST activity was determined in whole blood by spectrophotometry, and GST genotypes by multiplex PCR RFLP for 36 CF and 9 control children. Levels of glutathione in erythrocyte and vitamins A, E and C in plasma were measured by HPLC. RESULTS: No difference in GST activity and no relationship between GST activity and antioxidant levels were observed in CF children as compared to controls. However, GST activity was lower in CF children with severe clinical status and infection, and the frequency of GSTP1 wild type genotype AA, prevalent in uninfected CF children (75%), decreased in infected ones (33%). CONCLUSION: GST activity and genotype could play an important role in modulating P. aeruginosa lung infection in CF patients.