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• Residual stress mapping provides an efficient alternative to welding process simulations. • Upper bound distributions of experimental data secure conservatism in integrity assessments. • Internal equilibrium in the FE model play important role in residual stress mapping. Residual stress is a factor which potentially affects the integrity of welded components. We have developed a methodology of assessment to establish the state of residual stress in a butt-welded plate by using a limited set of experimental measurements obtained using neutron diffraction. The unique longitudinal and transverse residual stress components, as a result of the welding process, are measured across the weld in three depths through the thickness. The measured residual stresses are then used to estimate a stress distribution for each stress component. The estimated stress distribution is then mapped to a finite element model of the weld plate, before adopting an iterative solution to reconstruct the residual stress fields. In addition, a traditional welding simulation is performed using the same weld plate details to predict and compare the residual stress distributions. It is shown that accurate residual stress field reconstruction is possible in and around the area of measurement using the limited measurement data from the neutron diffraction technique. In the estimated stress profiles, an upper-bound distribution is implemented in the weld and Heat Affected Zone (HAZ). This increases the efficiency and reduces the complexity of modelling. In the meantime, conservatism in the estimated stress is secured. [ABSTRACT FROM AUTHOR]

This paper reports on the adoption of TiB 2 as an inoculant to fabricate IN718 via the direct energy deposition (DED) process. Effective grain refinement and low texture were achieved in IN718/TiB 2 using a TiB 2 powder size of d 90 = 10 μm and mass fraction of 1.5 wt%. The use of low linear energy density (33.08 J/mm) produced IN718/TiB 2 deposits free from large grains (>300 μm), however at the cost of the formation of interlayer defects. By comparison, the large grains were present in deposits made with a linear energy density of 78.74 J/mm and also in deposits manufactured without an included inoculant. Production of deposits at lower energies without interlayer defects was possible by reducing the powder flow rate to 7 g/min. However, this caused a moderate increase in grain size. The TiB 2 inoculant reduced the Laves phase network by replacing it with homogeneously distributed Cr-, Mo-, Nb-, and B-enriched needle-shaped precipitates. Tensile strength increased by 300–500 MPa with TiB 2 addition, but at the cost of significant ductility drop, regardless of the deposition conditions. The IN718 deposit displayed many micro-cracks at the network of Laves phase during tensile loading, whereas micro-cracks in the IN718/TiB 2 occurred at the interface between the needle-shaped precipitates and the matrix. The strength enhancement in IN718/TiB 2 was by a combination of strengthening mechanisms: grain boundary, dislocation structure formation, Orowan-type and load transfer related to the needle-shaped precipitates. • Microstructure refinement of direct energy deposition IN718 was achieved using TiB 2 as an inoculant. • With 1.5 wt% TiB 2 addition, a refined microstructure with reduced texture and ∼80% strength enhancement was obtained. • The increase of geometrically necessary dislocations, Orowan strengthening, and grain refinement due to TiB 2 addition were the major strengthening contributors. • Powder flow rate was found to affect the densification of the IN718/TiB 2 deposits. [ABSTRACT FROM AUTHOR]

Plain bend bars made from FV566 martensitic stainless steel were extracted from the root of ex‐service power plant turbine blades and several industry‐relevant notch geometries were introduced. Some of the samples were shot peened. The notched bend bars were loaded plastically in the low‐cycle fatigue regime and finite element (FE) modeling carried out to investigate the effects of changing notch geometry, combined with shot peening, on fatigue behaviors such as crack initiation, short crack growth, and coalescence. Shot peening damaged the notch surface, accelerating initiation behaviors, but had a lifetime‐extending effect by retarding short crack growth in all tested notch geometries. At a total strain range higher than 1.2%, the lifetime extension benefit from shot peening was diminished due to compressive residual stress relaxation in the notch stress field. Notch geometry (and the associated varying constraint levels and stress/strain gradients) was found to have no notable difference on fatigue life when tested at identical notch‐root strain ranges. Highlights: Initiation activity increased with increasing strain range regardless of notch geometry. Surface damage from the shot peening increased initiation activity and lowered a/c ratios. Shot peening reduced the early short crack growth rate at lower ΔK by a factor of 10. Shot peening increased lifetimes up to a strain range of 0.8%–1.2%. [ABSTRACT FROM AUTHOR]

A recent biological study shows that the extremely good efficiency of fruit flies in finding food, despite their small brain, emerges by two distinct stimuli: smell and visual contrast. “contrast-based fruit fly optimization”, presented in this paper, is for the first time mimicking this fruit fly behaviour and developing it as a means to efficiently address multi-parameter optimization problems. To assess its performance a study was carried out on ten mathematical and three truss optimization problems. The results are compared to those obtained using twelve state-of-the-art optimization algorithms and confirm its good and robust performance. A sensitivity analysis and an evaluation of its performance under parallel computing were conducted. The proposed algorithm has only a few tuning parameters, is intuitive, and multi-faceted, allowing application to complex n-dimensional design optimization problems. [ABSTRACT FROM AUTHOR]

The detection of illicit radiological materials is critical to establishing a robust second line of defence in nuclear security. Neutron-capture prompt-gamma activation analysis (PGAA) can be used to detect multiple radioactive materials across the entire Periodic Table. However, long detection times and a high rate of false positives pose a significant hindrance in the deployment of PGAA-based systems to identify the presence of illicit substances in nuclear forensics. In the present work, six different machine-learning algorithms were developed to classify radioactive elements based on the PGAA energy spectra. The model performance was evaluated using standard classification metrics and trend curves with an emphasis on comparing the effectiveness of algorithms that are best suited for classifying imbalanced datasets. We analyse the classification performance based on Precision, Recall, F1-score, Specificity, Confusion matrix, ROC-AUC curves, and Geometric Mean Score (GMS) measures. The tree-based algorithms (Decision Trees, Random Forest and AdaBoost) have consistently outperformed Support Vector Machine and K-Nearest Neighbours. Based on the results presented, AdaBoost is the preferred classifier to analyse data containing PGAA spectral information due to the high recall and minimal false negatives reported in the minority class. [ABSTRACT FROM AUTHOR]

This paper proposes a transfer learning approach to recalibrate our previously developed Wheel Odometry Neural Network (WhONet) for vehicle positioning in environments where Global Navigation Satellite Systems (GNSS) are unavailable. The WhONet has been shown to possess the capability to learn the uncertainties in the wheel speed measurements needed for correction and accurate positioning of vehicles. These uncertainties may be manifested as tyre pressure changes from driving on muddy and uneven terrains or wheel slips. However, a common cause for concern for data-driven approaches, such as the WhONet model, is usually the inability to generalise the models to a new vehicle. In scenarios where machine learning models are trained in a specific domain but deployed in another domain, the model’s performance degrades. In real-life scenarios, several factors are influential to this degradation, from changes to the dynamics of the vehicle to new pattern distributions of the sensor’s noise, and bias will make the test sensor data vary from training data. Therefore, the challenge is to explore techniques that allow the trained machine learning models to spontaneously adjust to new vehicle domains. As such, we propose the Recalibrated-Wheel Odometry neural Network, based on transfer learning, that adapts the WhONet model from its source domain (a vehicle and environment on which the model is initially trained) to the target domain (a new vehicle on which the trained model is to be deployed). Through a performance evaluation on several GNSS outage scenarios—short-term complex driving scenarios such as on roundabouts, sharp cornering, hard-brake and wet roads (drifts), and on longer-term GNSS outage scenarios of 30s, 60s, 120s and 180s duration—we demonstrate that a model trained in the source domain does not generalise well to a new vehicle in the target domain. However, we show that our new proposed framework improves the generalisation of the WhONet model to new vehicles in the target domains by an average of 32% (i.e. 32% reduction in the vehicle position error estimation across the scenarios investigated). [ABSTRACT FROM AUTHOR]

Selective-laser-melting (SLM) is a powder-bed fusion additive-manufacturing process that has the potential to deliver three-dimensional complex parts with mechanical properties comparable or superior to parts produced via traditional manufacturing using cast and wrought alloys. Concerns for metallic parts built via SLM are the process-induced residual stresses, and anisotropic mechanical properties. This paper investigates the effect of residual stresses on the fatigue crack growth rate of SLM Ti6Al4V in as-built and stress-relieved conditions. Neutron diffraction and the contour method are employed to measure residual stresses in compact-tension samples. Neutron diffraction results are in good agreement with the contour method. It was found that tensile stresses are present at the notch root and the free edge areas, and compressive stress is seen in the middle of the sample. The tensile stresses in the as-built condition resulted in a higher fatigue crack growth rate. After stress relieving by heat treatment, the tensile residual stress diminished by around 90%, resulting in decreased crack growth rate. The build direction was seen to affect the crack growth rate, although the trend was different between the as-built and stress-relieved conditions. [ABSTRACT FROM AUTHOR]

• Two α-phase variants are formed in Ti-5553 alloy: one above and one below 550 °C. • The formation of α-phase starts with a cooling rate of 0.5 °C/s. • Slow cooling can be used to obtain similar hardness than fast cooling plus ageing. We performed high-throughput in situ electrical resistance measurement experimentation to understand the effect of cooling rate on the phase transformation behaviour of Ti–5Al–5Mo–5V–3Cr β-Ti alloy. The results suggest the presence of two α-phase variants and that the formation of α-phase starts with a cooling rate of 0.5 °C/s. A slow cooling rate (0.1 °C/s) can be used to obtain similar microstructure and hardness (∼430 Hv) than fast cooling followed by an ageing treatment. [ABSTRACT FROM AUTHOR]

The present study discusses the mechanical behaviour and modelling of a prototype automotive magnetorheological (MR) damper, which presents different viscous damping coefficients in jounce and rebound. The force generated by the MR damper is measured at different velocities and electrical currents, and a modified damper model is proposed to improve fitting of the experimental data. The model is calibrated by means of parameter identification, and for this purpose a new swarm intelligence algorithm is proposed, that we call the contrast-based Fruit Fly Optimisation Algorithm (c-FOA). The performance of c-FOA is compared with that of Genetic Algorithms, Particle Swarm Optimisation, Differential Evolution and Artificial Bee Colony. The comparison is made on the basis of no a-priori knowledge of the damper model parameters range. The results confirm the good performance of c-FOA under parametric range uncertainty. A sensitivity analysis discusses c-FOA’s performance with respect to its tuning parameters. Finally, a ride comfort simulation study quantifies the discrepancies in the results, for different identified damper model sets. The discrepancies underline the importance of accurately describing MR damper nonlinear behaviour, considering that virtual sign-off processes are increasingly gaining momentum in the automotive industry. [ABSTRACT FROM AUTHOR]

Predictive monitoring supports the a priori scheduling of critical component maintenance and contributes significantly in attaining a safe yet economic operation and management of complex energy systems by mitigating the risk of accidents and minimizing the number of operational pauses. The current work studies the learning ability of probabilistic kernel machines, and more particularly of Gaussian Processes (GP) equipped with various kernels for the estimation of weld residual stress profiles of stainless steel pipe welds. The GP models are tested on experimentally-obtained data of axial and hoop residual stresses in two different stainless-steel pipes. The results exhibit the ability of GP to accurately predict the weld residual stress profile in the axial and hoop direction by providing a predictive distribution, i.e., mean and variance values. Furthermore, performance of GP is compared to a non-probabilistic kernel machine, such as support vector regression (SVR) equipped with the same kernels, and to multivariate linear regression (MLR). Comparison results exhibit the robustness of GP over SVR and MLR with respect to prediction accuracy of weld residual stress in terms of root mean square error. With respect to a second metric, namely, correlation coefficient between measured and predicted values, GP is superior to SVR and MLR in the majority of the cases. [ABSTRACT FROM AUTHOR]

This paper presents 2D mapping of residual strains, induced by cold expansion and laser shock peening processing of aluminium alloy samples, by using Bragg edge neutron transmission. Neutron transmission uses information contained in the neutron beam transmitted through a sample. It is shown that neutron transmission strain mapping with high spatial resolution can provide important insights into the distribution of residual strains associated with processing of materials. The residual strain field around a cold-expanded hole can be revealed in detail, as can be the residual strain profile associated with laser peening. Results are correlated with measurements obtained by conventional neutron diffraction and incremental hole drilling. The residual strain variation around the cold-expanded hole and the depth of compressive residual strain generated by the peening process were captured with high spatial resolution, showing the advantages of neutron transmission over other well-established strain measurement methods by non-destructively generating a map of residual strains over a large area. [ABSTRACT FROM AUTHOR]

Making laser powder bed fusion (L-PBF) additive manufacturing process sustainable requires effective powder recycling. Recycling of Ti6Al4V powder in L-PBF can lead to powder oxidation, however, such impact on laser-matter interactions, process, and defect dynamics during L-PBF are not well understood. This study reveals and quantifies the effects of processing Ti6Al4V powders with low (0.12 wt%) and high (0.40 wt%) oxygen content during multilayer thin-wall L-PBF using in situ high speed synchrotron X-ray imaging. Our results reveal that high oxygen content Ti6Al4V powder can reduce melt ejections, surface roughness, and defect population in the built parts. With increasing oxygen content in the part, there is an increase in microhardness due to solid solution strengthening and no significant change in the microstructure is evident. [Display omitted] • Oxidised Ti6Al4V powder (0.40 wt% oxygen) has a lower laser absorptivity than the virgin powder. • Oxides in the melt pool could reduce melt pool instabilities and droplet spatter, and improve processability. • Laser powder bed fusion of oxidised powder reduces surface roughness and porosity, enhancing printability of Ti6Al4V. [ABSTRACT FROM AUTHOR]

Bonded crack retarders (BCR) are of particular interest in the aerospace applications for improving fatigue performance of airframe structural assemblies. In respect of structural integrity, a reinforcing strap will require additional fixing by means of riveting or bolting to ensure fail-safety. Cold expansion is currently the common practice of increasing the fatigue performance of fastener holes. Thermal residual stresses introduced during the adhesive curing process at 120 °C for strap bonding are of potential concern as they may affect the cold expansion stresses and thereby the fatigue crack growth performance of the fastener hole and reinforced structural assembly. In this paper, Single-Edge-Notched Tension (SENT) specimens are made of aluminium alloy 2624-T351. Fibre metal laminate GLARE is used as BCR strap. SENT specimens with BCR and with BCR plus an interference fit fastener are used to investigate the fatigue crack growth performance. Residual stress was measured by neutron diffraction method on specimens with BCR plus fastener. It is found that the GLARE strap provides a 2.3 × improvement in life comparing to a plain specimen, and a 1.75 × life improvement when a fastener is installed in a cold expanded hole. [ABSTRACT FROM AUTHOR]

The quest for more efficient real-time detection of anomalies in time series data is critically important in numerous applications and systems ranging from intelligent transportation, structural health monitoring, heart disease, and earthquake prediction. Although the range of application is wide, anomaly detection algorithms are usually domain specific and build on experts’ knowledge. Here a new signal processing algorithm – inspired by the deep learning paradigm – is presented that combines wavelets, neural networks, and Hilbert transform. The algorithm performs robustly and is transferable. The proposed neural network structure facilitates learning short and long-term pattern interdependencies; a task usually hard to accomplish using standard neural network training algorithms. The paper provides guidelines for selecting the neural network's buffer size, training algorithm, and anomaly detection features. The algorithm learns the system's normal behavior and does not require the existence of anomalous data for assessing its statistical significance. This is an essential attribute in applications that require customization. Anomalies are detected by analysing hierarchically the instantaneous frequency and amplitude of the residual signal using probabilistic Receiver Operating Characteristics. The method is shown to be able to automatically detect anomalies in the Seismic Electrical Signal that could be used to predict earthquake activity. Furthermore, the method can be used in combination with crowdsourcing of smartphone data to locate road defects such as potholes and bumps for intervention and repair. [ABSTRACT FROM AUTHOR]

This paper presents results of fatigue crack growth testing of aluminium alloy 2624-T351 reinforced by bonded crack retarders made of GLARE fibre-metal laminate. Specimens were tested at room temperature, 70 °C and −60 °C. Better performance of the crack retarders in terms of increased fatigue life was achieved at room temperature than at the two temperature extremes. This is attributed to a combined effect of change in the fatigue crack growth rate at temperature in the substrate material, and residual stress generated at temperatures above or below room temperature. The change in fatigue crack growth rate was measured, and the substrate deformation and the stress intensity factors at temperature were calculated by Finite Element Analysis. In addition, the effect of thermal cycling on fatigue crack growth rate was investigated by exposing the specimens to repeated thermal cycles between 70 °C and −60 °C prior to fatigue testing. It is concluded that the pre-test thermal cycling has little effect on the fatigue crack growth rate. [ABSTRACT FROM AUTHOR]

To inform the design of superior transformation-induced plasticity (TRIP) steels, it is important to understand what happens at the microstructural length scales. In this study, strain-induced martensitic transformation is studied by in situ digital image correlation (DIC) in a scanning electron microscope. Digital image correlation at submicron length scales enables mapping of transformation strains with high confidence. These are correlated with electron backscatter diffraction (EBSD) prior to and post deformation process to get a comprehensive understanding of the strain-induced transformation mechanism. The results are compared with mathematical models for enhanced prediction of strain-induced martensitic phase transformation. [ABSTRACT FROM AUTHOR]

• Quantitative assessment of strain in a bolt/nut assembly using neutron imaging. • Measurements for normal and corroded parts for different bolt preload conditions. • Quantitative analysis of the effect of corrosion on the loss of preloaded tension. • Quantitative analysis of the residual strain on single bolts. Failures in bolted structural connections have caused in the past the collapse of various steel structures exposed to weather conditions, including wind turbine towers, oil and gas platforms, and bridges. Corrosion and the resulting loss of preloaded tension in the bolted connection were the root cause of such catastrophic failures in many cases. However, it is still not fully understood how strain is re-distributed in corroded bolted connections, nor how different factors influence the redistribution. Measuring non-destructively the strain inside the assembly has been the main obstacle. To this end, in this paper, we employed energy-resolved neutron transmission imaging and we present strain maps in corroded bolted connections for the first time. We examined and compared the strain distribution measurements in corroded and non-corroded assemblies for different bolt-tightening techniques. The specimens under investigation were artificially corroded without introducing any additional mechanical loads. The resulting strain maps illustrate how strain is re-distributed and provide insight into the influence of the bolt-tightening method. [ABSTRACT FROM AUTHOR]

An extensive study on the fatigue performance of friction stir welded DH36 steel was carried out. The main focus of this experimental testing programme was fatigue testing accompanied by tensile tests, geometry measurements, hardness and residual stress measurements, and fracture surface examination. The S – N curve for friction stir butt welded joints was generated and compared with the International Institute of Welding recommendations for conventional fusion butt welds. Friction stir welds of marine grade steel exceeded the relevant rules for fusion welding. This newly developed S – N curve is being proposed for use in the relevant fatigue assessment guidelines for friction stir welding of low alloy steel. Fracture surfaces were examined to investigate the fatigue failure mechanism, which was found to be affected by the processing features generated by the friction stir welding tool. [ABSTRACT FROM AUTHOR]

Mechanical surface treatment technologies such as laser peening and cavitation peening require detailed characterization, including residual stress analysis, to optimize their processing parameters. Recent developments at neutron facilities allow non-destructive 2-dimensional residual strain mapping through Bragg edge imaging, which provides specific advantages over more established methods. The present work highlights the application of Bragg edge neutron imaging for the study of mechanical surface treatments, through determination of lattice spacing distributions by energy-resolved radiography. Through three different examples, the unique capabilities of the method are demonstrated, particularly for providing near surface residual strain maps within samples with complex geometries with relatively high spatial resolution. By providing a comparison with X-ray diffraction and neutron diffraction results, the present work emphasizes the potential of Bragg edge neutron imaging as a tool for surface treatment research. [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights: [•] In situ powder neutron diffraction to study precipitate formation in ODS steel. [•] First real time observation of nano-precipitate formation during processing. [•] Y2O3 particles were fully dissolved into steel matrix during mechanical alloy. [•] The precipitation occurred during annealing of as-milled powder above 900°C. [ABSTRACT FROM AUTHOR]

Abstract: Time-dependent anelastic deformation mechanisms arise in austenitic stainless steel when load is removed during a high-temperature creep test. This phenomenon is investigated by conducting creep tests, with intermittent load removal, on AISI Type 316H austenitic stainless steel at 550 and 650°C, supported by in situ measurement of creep-induced intergranular residual strains by neutron diffraction. All the cyclic tests exhibit anelastic behaviour on unloading and develop substantially lower load-on creep strain rates, reduced ductility and longer rupture times than baseline steady-load creep tests at similar conditions. The mechanisms underlying the observed anelastic behaviour and changes in macroscopic creep properties are discussed with reference to the development of intergranular strains and dislocation behaviour. [Copyright &y& Elsevier]

• The LSPned residual stress filed of Ti-6Al-7Nb alloy was characterized by IHD method. • Laser energy & overlap are proportional to the magnitude of the near-surface residual stress. • Laser energy & overlap are in proportion to the affecting depth. • The LSPned residual stress was predicted by ANN and the results are in good agreement with IHD data. Prolonged usage can lead to fatigue failures in prosthetic implants. This is an emerging concern for the prosthesis designer and as well as for end-users. Laser shock peening (LSP) can be used to improve the life of prostheses by introducing a compressive surface stress that delays or arrests the initiation of cracks. We report measurements of residual stresses induced by LSP in a medical-grade Ti-6Al-7Nb alloy. In this paper, the LSP introduced residual stress field was characterized by using Incremental Hole Drilling (IHD) with predictive modelling using an Artificial Neural Network (ANN). The Ti-6Al-7Nb samples were processed by a pulsed Nd: YAG laser with laser energy of 3 J, 5 J and 7 J with overlaps of 33%, 50% and 67%. The IHD results show that a range of −42 MPa to −516 MPa compressive residual stresses are formed at the near surface. The residual stress value and affecting layer depth are proportional to laser energy and overlap. What is more, a gradient descent learning algorithm was employed in ANN prediction. The microhardness, laser energy, overlap and depth are set as input parameters while the residual stresses are output. The predicted results have a good agreement with the experimental data with accuracy of 96.16% and 95.16%. It proves that ANN is applicable in LSP residual stress simulation when the experimental data is limited. The work in this paper enables to have subsequent predictions of fatigue life of implants via residual stress fields for future applications. [ABSTRACT FROM AUTHOR]

The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics and a surge in gastrointestinal diseases 1,2 has fuelled efforts to catalogue cells constituting gastrointestinal tissues in health and disease 3 . Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy gastrointestinal tract in development and in adulthood. We uniformly processed 385 samples from 189 healthy controls using a newly developed automated quality control approach (scAutoQC), leading to a healthy reference atlas with approximately 1.1 million cells and 136 fine-grained cell states. We anchor 12 gastrointestinal disease datasets spanning gastrointestinal cancers, coeliac disease, ulcerative colitis and Crohn's disease to this reference. Utilizing this 1.6 million cell resource (gutcellatlas.org), we discover epithelial cell metaplasia originating from stem cells in intestinal inflammatory diseases with transcriptional similarity to cells found in pyloric and Brunner's glands. Although previously linked to mucosal healing 4 , we now implicate pyloric gland metaplastic cells in inflammation through recruitment of immune cells including T cells and neutrophils. Overall, we describe inflammation-induced changes in stem cells that alter mucosal tissue architecture and promote further inflammation, a concept applicable to other tissues and diseases., Competing Interests: Competing interests: S.A.T. is a scientific advisory board member of ForeSite Labs, OMass Therapeutics, a co-founder and equity holder of TransitionBio and EnsoCell Therapeutics, a non-executive director of 10x Genomics and a part-time employee of GlaxoSmithKline. R.E. is an equity holder in EnsoCell. P.K. has consulted for AstraZeneca, UCB, Biomunex and Infinitopes. N.M.P reports consulting fees from Infinitopes. J.S.-R. reports funding from GSK, Pfizer and Sanofi and fees/honoraria from Travere Therapeutics, Stadapharm, Astex, Owkin, Pfizer, Moderna and Grunenthal. A.S. is the recipient of research grants from Roche-Genentech, Abbvie, GSK, Scipher Medicine, Pfizer, Alimentiv, Boehringer Ingelheim and Agomab and has received consulting fees from Genentech, GSK, Pfizer, HotSpot Therapeutics, Alimentiv, Agomab, Goodgut and Orikine. R.E. and S.A.T are inventors on the patent GB2412853.0 filed in the UK, some components of which are related to this work. All other authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Variation in access to parenteral nutrition (PN) in patients with intestinal failure secondary to malignant bowel obstruction (MBO) exists due to differing practice, beliefs and resource access. We aimed to examine differences in nutritional care pathways and outcomes, by referral to nutrition team for PN in patients with MBO., Methods: This is a retrospective cohort study of MBO adults admitted to eight UK hospitals within a year and 1 year follow-up. Demographic, nutritional and medical data were analysed by comparing patients referred (R) or not referred (NR) for PN. Differences between groups were tested by Kruskal-Wallis, Chi-Squared tests and multi-level regression and survival using Cox regression., Results: 232 patients with 347 MBO admissions [median 66yr, (IQR: 55-74yrs), 67 % female], 79/232 patients were referred for PN (R group). Underlying primary malignancies of gynaecological and gastrointestinal origin predominated (71 %) and 78 % with metastases. Those in the NR group were found to be older, weigh more on admission, and more likely to be treated conservatively compared to those in the R group. For 123 (35 %) admissions, patients were referred to a nutrition team, and for 204 (59 %) admissions, patients were reviewed by a dietician. Multi-disciplinary team discussion and dietetic contact were more likely to occur in the R group-123/347 admissions (R vs NR group: 27 % vs. 7 %, P = 0.001; 95 % vs 39 %, P < 0.0001). Median admission weight loss was 8 % (IQR: 0 to 14). 43/123 R group admissions received inpatient PN only, with 32 patients discharged or already established on home parenteral nutrition. Overall survival was 150 days (126-232) with no difference between R/NR groups., Conclusion: In this multi-centre study evaluating nutritional care management of patients with malignant bowel obstruction, only 1 in 3 admissions resulted in a referral to the nutrition team for PN, and just over half were reviewed by a dietician. Further prospective research is required to evaluate possible consequences of these differential care pathways on clinical outcomes and quality of life., Competing Interests: Declaration of competing interest Pinal Patel's Research Post was funded by Calea, Fresenius Kabi, UK., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize microbial metabolites through a semi-invariant T cell receptor (TCR). Major questions remain regarding the extent of human MAIT cell functional and clonal diversity. To address these, we analyzed the single-cell transcriptome and TCR repertoire of blood and liver MAIT cells and developed functional RNA-sequencing, a method to integrate function and TCR clonotype at single-cell resolution. MAIT cell clonal diversity was comparable to conventional memory T cells, with private TCR repertoires shared across matched tissues. Baseline functional diversity was low and largely related to tissue site. MAIT cells showed stimulus-specific transcriptional responses in vitro, with cells positioned along gradients of activation. Clonal identity influenced resting and activated transcriptional profiles but intriguingly was not associated with the capacity to produce IL-17. Overall, MAIT cells show phenotypic and functional diversity according to tissue localization, stimulation environment and clonotype., (© 2023. The Author(s).)

Interactions with commensal microbes shape host immunity on multiple levels and play a pivotal role in human health and disease. Tissue-dwelling, antigen-specific T cells are poised to respond to local insults, making their phenotype important in the relationship between host and microbes. Here we show that MHC-II restricted, commensal-reactive T cells in the colon of both humans and mice acquire transcriptional and functional characteristics associated with innate-like T cells. This cell population is abundant and conserved in the human and murine colon and endowed with polyfunctional effector properties spanning classic Th1- and Th17-cytokines, cytotoxic molecules, and regulators of epithelial homeostasis. T cells with this phenotype are increased in ulcerative colitis patients, and their presence aggravates pathology in dextran sodium sulphate-treated mice, pointing towards a pathogenic role in colitis. Our findings add to the expanding spectrum of innate-like immune cells positioned at the frontline of intestinal immune surveillance, capable of acting as sentinels of microbes and the local cytokine milieu., (© 2022. The Author(s).)

Vδ2 + γδT cells are unconventional T cells that can be activated by cytokines without TCR signaling. Adenovirus vaccine vectors activated Vδ2 + γδT cells in an interleukin 18-, TNF-, and type I interferon-dependent manner. This stimulatory capacity was associated with adenovirus vectors of non-species C origin, including the ChAdOx1 vaccine platform., (© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

Background & Aims: The pathogenesis of immune checkpoint inhibitor (ICI)-colitis remains incompletely understood. We sought to identify key cellular drivers of ICI-colitis and their similarities to idiopathic ulcerative colitis, and to determine potential novel therapeutic targets., Methods: We used a cross-sectional approach to study patients with ICI-colitis, those receiving ICI without the development of colitis, idiopathic ulcerative colitis, and healthy controls. A subset of patients with ICI-colitis were studied longitudinally. We applied a range of methods, including multiparameter and spectral flow cytometry, spectral immunofluorescence microscopy, targeted gene panels, and bulk and single-cell RNA sequencing., Results: We demonstrate CD8 + tissue resident memory T (T RM ) cells are the dominant activated T cell subset in ICI-colitis. The pattern of gastrointestinal immunopathology is distinct from ulcerative colitis at both the immune and epithelial-signaling levels. CD8 + T RM cell activation correlates with clinical and endoscopic ICI-colitis severity. Single-cell RNA sequencing analysis confirms activated CD8 + T RM cells express high levels of transcripts for checkpoint inhibitors and interferon-gamma in ICI-colitis. We demonstrate similar findings in both anti-CTLA-4/PD-1 combination therapy and in anti-PD-1 inhibitor-associated colitis. On the basis of our data, we successfully targeted this pathway in a patient with refractory ICI-colitis, using the JAK inhibitor tofacitinib., Conclusions: Interferon gamma-producing CD8 + T RM cells are a pathological hallmark of ICI-colitis and a novel target for therapy., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Tissue-resident memory T (T RM ) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However, transcriptional heterogeneity of human intestinal T RM cells remains undefined. Here, we investigate transcriptional and functional heterogeneity of human T RM cells through study of donor-derived T RM cells from intestinal transplant recipients. Single-cell transcriptional profiling identifies two transcriptional states of CD8 + T RM cells, delineated by ITGAE and ITGB2 expression. We define a transcriptional signature discriminating these populations, including differential expression of cytotoxicity- and residency-associated genes. Flow cytometry of recipient-derived cells infiltrating the graft, and lymphocytes from healthy gut, confirm these CD8 + T RM phenotypes. CD8 + CD69 + CD103 + T RM cells produce interleukin-2 (IL-2) and demonstrate greater polyfunctional cytokine production, whereas β2-integrin + CD69 + CD103 - T RM cells have higher granzyme expression. Analysis of intestinal CD4 + T cells identifies several parallels, including a β2-integrin + population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal CD4 + and CD8 + T RM cells., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mucosal-associated invariant T (MAIT) cells are innate-like T cells abundant in humans that can be activated in a TCR-independent manner by inflammatory and antiviral cytokines. In humans, the capacity for TCR-independent activation is functionally linked to a transcriptional program that can be identified by the expression of the C-type lectin receptor, CD161. In addition to MAIT cells, it has been demonstrated that a subset of γδT cells expresses CD161 and can be activated by TCR-independent cytokine stimulation. In this study, we sought to clarify the nature of cytokine-responsive human γδT cells. We could link CD161 expression on Vδ2 + versus Vδ1 + γδT cells to the observation that Vδ2 + γδT cells, but not Vδ1 + γδT cells, robustly produced IFN-γ upon stimulation with a variety of cytokine combinations. Interestingly, both CD161 + and CD161 - Vδ2 + γδT cells responded to these stimuli, with increased functionality within the CD161 + subset. This innate-like responsiveness corresponded to high expression of PLZF and IL-18Rα, analogous to MAIT cells. Vδ2 + γδT cells in human duodenum and liver maintained a CD161 + IL-18Rα + phenotype and produced IFN-γ in response to IL-12 and IL-18 stimulation. In contrast to MAIT cells, we could not detect IL-17A production but observed higher steady-state expression of Granzyme B by Vδ2 + γδT cells. Finally, we investigated the frequency and functionality of γδT cells in the context of chronic hepatitis C virus infection, as MAIT cells are reduced in frequency in this disease. By contrast, Vδ2 + γδT cells were maintained in frequency and displayed unimpaired IFN-γ production in response to cytokine stimulation. In sum, human Vδ2 + γδT cells are a functionally distinct population of cytokine-responsive innate-like T cells that is abundant in blood and tissues with similarities to human MAIT cells.