Automating the referral pathways for Multiple Myeloma through a Web Application and XMDD

Multiple Myeloma (MM), a type of bone marrow cancer, is diagnosed by measuring monoclonal proteins, paraproteins (PP), and serum-free light chains (SFLC) in the blood. These proteins can be detected in healthy individuals at a lower level. This condition is called Monoclonal Gammopathy of Uncertain Significance (MGUS). MGUS is associated with a risk of progression to MM at a rate of 1-2% per year. Early diagnosis of MM correlates with improved overall survival for patients, so early referral of suspect cases is important. Two risk factors determine the risk of progression: a high-level PP (>15g/l) and an abnormal SFLC ratio. This risk stratification process enables General Practitioners (essentially, the family doctors) to manage the patients with low-risk MGUS and provides clear referral pathways for intermediate and high-risk MGUS patients. There are a reference algorithm and a scoring system for patient referrals with possible Multiple Myeloma, that in the current practice are processed manually by trained healthcare staff. In collaboration with the Haematology experts at the University Hospital Limerick and the SCCE group in Computer Science, we designed and implemented a software application that improves and streamlines the current process. This (online) application is developed with modern XMDD technology, using the DIME low-code application development tool. The application faithfully maps the reference algorithm in an automated way and applies it to a consultation data-set. The novelty consists in the adopted technologies, that improve the early validation and correctness of the software, and ease the human understanding and the modification turnaround of the application

Analysis of ligation and DNA binding by Escherichia coli DNA ligase (LigA).

NAD+-dependent DNA ligases are essential enzymes in bacteria, with the most widely studied of this class of enzymes being LigA from Escherichia coli. NAD+-dependent DNA ligases comprise several discrete structural domains, including a BRCT domain at the C-terminus that is highly-conserved in this group of proteins. The over-expression and purification of various fragments of E. coli LigA allowed the investigation of the different domains in DNA-binding and ligation by this enzyme. Compared to the full-length protein, the deletion of the BRCT domain from LigA reduced in vitro ligation activity by 3-fold and also reduced DNA binding. Using an E. coli strain harbouring a temperature-sensitive mutation of ligA, the over-expression of protein with its BRCT domain deleted enabled growth at the non-permissive temperature. In gel-mobility shift experiments, the isolated BRCT domain bound DNA in a stable manner and to a wider range of DNA molecules compared to full LigA. Thus, the BRCT domain of E. coli LigA can bind DNA, but it is not essential for DNA nick-joining activity in vitro or in vivo

The Curatorial Incubator : v.12

"So boasts James Joyce in A Portrait of the Artist as a Young Man, that canonical tale of a sensitive, artistic youth coming of age. is year, e Curatorial Incubator, v.12 has asked emerging curators to get a little naughty and put a contemporary spin on this classic by considering media artworks that come together to create A Portrait of the Artist as a Young Brat. Happily, the programs they have assembled are as brash and fearless as Stephen Dedalus, hero of Joyce’s 1916 Modernist classic." -- p. 2

The strategic role of reinsurance in the United Kingdom’s (UK) non-life insurance market

We demonstrate that by increasing the level of reinsurance, primary insurers increase their product-market share at the expense of rivals with lower reinsurance coverage in five main lines of insurance in the United Kingdom’s (UK) non-life insurance market. We use panel data drawn from statutory filings made by non-life insurers to the then UK regulator (FSA) over 1985 to 2010 period. We find that the influence of reinsurance and other financial variables on insurers’ growth in product-market share varies across lines of insurance business. Since reinsurance impacts on product-market outcomes in competitive non-life insurance industry, we conclude that reinsurance performs an important strategic function in insurance markets

Time resolved in-situ multi-contrast X-ray imaging of melting in metals

In this work, the application of a time resolved multi-contrast beam tracking technique to the investigation of the melting and solidification process in metals is presented. The use of such a technique allows retrieval of three contrast channels, transmission, refraction and dark-field, with millisecond time resolution. We investigated different melting conditions to characterize, at a proof-of-concept level, the features visible in each of the contrast channels. We found that the phase contrast channel provides a superior visibility of the density variations, allowing the liquid metal pool to be clearly distinguished. Refraction and dark-field were found to highlight surface roughness formed during solidification. This work demonstrates that the availability of the additional contrast channels provided by multi-contrast X-ray imaging delivers additional information, also when imaging high atomic number specimens with a significant absorption

X-ray phase-contrast microtomography of soft tissues using a compact laboratory system with two-directional sensitivity

X-ray microtomography is a nondestructive, three-dimensional inspection technique applied across a vast range of fields and disciplines, ranging from research to industrial, encompassing engineering, biology, and medical research. Phase-contrast imaging extends the domain of application of x-ray microtomography to classes of samples that exhibit weak attenuation, thus appearing with poor contrast in standard x-ray imaging. Notable examples are low-atomic-number materials, like carbon-fiber composites, soft matter, and biological soft tissues. We report on a compact and cost-effective system for x-ray phase-contrast microtomography. The system features high sensitivity to phase gradients and high resolution, requires a low-power sealed x-ray tube, a single optical element, and fits in a small footprint. It is compatible with standard x-ray detector technologies: in our experiments, we have observed that single-photon counting offered higher angular sensitivity, whereas flat panels provided a larger field of view. The system is benchmarked against known-material phantoms, and its potential for soft-tissue three-dimensional imaging is demonstrated on small-animal organs: a piglet esophagus and a rat heart. We believe that the simplicity of the setup we are proposing, combined with its robustness and sensitivity, will facilitate accessing quantitative x-ray phase-contrast microtomography as a research tool across disciplines, including tissue engineering, materials science, and nondestructive testing in general

Lipidomics analysis of juveniles' blue mussels (Mytilus edulis L. 1758), a key economic and ecological species

Blue mussels (Mytilus edulis L. 1758) are important components of coastal ecosystems and in the economy of rural and coastal areas. The understanding of their physiological processes at key life stages is important both within food production systems and in the management of wild populations. Lipids are crucial molecules for bivalve growth, but their diversity and roles have not been fully characterized. In this study, traditional lipid profiling techniques, such as fatty acid (FA) and lipid class analysis, are combined to un-targeted lipidomics to elucidate the lipid metabolism in newly settled spat fed on a range of diets. The evaluated diets included single strains treatments (Cylindrotheca fusiformis CCAP 1017/2 –CYL, Isochrysis galbana CCAP 927/1– ISO, Monodopsis subterranean CCAP 848/1 –MONO, Nannochloropsis oceanica CCAP 849/10– NANNO) and a commercial algae paste (SP). Spat growth was influenced by the diets, which, according to their efficacy were ranked as follows: ISO>NANNO/CYL>SP>MONO. A higher triacylglycerols (TG) content, ranging from 4.23±0.82 μg mgashfree Dry weight (DW)-1 at the beginning of the trial (T0) to 51±15.3 μg mgashfreeDW-1 in ISO, characterised significant growth in the spat, whereas, a reduction of TG (0.3±0.08 μg mgashfreeDW-1 in MONO), mono unsaturated FA–MUFA (from 8.52±1.02 μg mgFAashfreeDW-1 at T0 to 2.81±1.02 μg mgFAashfreeDW-1 in MONO) and polyunsaturated FA–PUFA (from 17.57±2.24 μg mgFAashfreeDW-1 at T0 to 6.19±2.49 μg mgFAashfreeDW-1 in MONO) content characterised poor performing groups. Untargeted lipidomics evidenced how the availability of dietary essential PUFA did not influence only neutral lipids but also the membrane lipids, with changes in lipid molecular species in relation to the essential PUFA provided via the diet. Such changes have the potential to affect spat production cycle and their ability to respond to the surrounding environment. This study evidenced the advantages of coupling different lipid analysis techniques, as each technique disclosed relevant information on nutritional requirements of M. edulis juveniles, expanding the existing knowledge on the physiology of this important species

Readout and Control of a Single Nuclear Spin with a Metastable Electron Spin Ancilla

Electron and nuclear spins associated with point defects in insulators are promising systems for solid-state quantum technology1, 2, 3. The electron spin is usually used for readout and addressing, and nuclear spins are used as exquisite quantum bits4, 5 and memory systems3, 6. With these systems, single-shot readout of single nuclear spins5, 7 as well as entanglement4, 8, 9, aided by the electron spin, have been shown. Although the electron spin in this example is essential for readout, it usually limits the nuclear spin coherence10, leading to a quest for defects with spin-free ground states9, 11. Here, we isolate a hitherto unidentified defect in diamond and use it at room temperature to demonstrate optical spin polarization and readout with exceptionally high contrast (up to 45%), coherent manipulation of an individual excited triplet state spin, and coherent nuclear spin manipulation using the triplet electron spin as a metastable ancilla. We demonstrate nuclear magnetic resonance and Rabi oscillations of the uncoupled nuclear spin in the spin-free electronic ground state. Our study demonstrates that nuclei coupled to single metastable electron spins are useful quantum systems with long memory times, in spite of electronic relaxation processes.Engineering and Applied Science