University of Birmingham

This paper proposes a platform for robots to learn disassembly tasks based on reinforcement learning (RL) techniques. The platform is demonstrated by a robot learning the skill of removing a bolt along a door-chain groove in a data-driven way, where the clearance between the bolt and the groove is less than 1mm. Furthermore, the relationship between the performance of the learned skills and the precision of the robot is studied with a method to control the robot's precision by adding uncorrelated zero-mean Gaussian noise to the robot's actions. Finally, the transferability of the learned skills among robots with different precisions is empirically studied. It has been found that skills learned by a low-precision robot can perform better on a robot with higher precision, and skills learned by a high-precision robot have worse performance on robots with lower precision.

The Coronavirus Disease-2019 (COVID-19) pandemic has had a dramatic impact on transplantation services. A pandemic on such a scale had never been seen before in modern times. Without any prior experience, healthcare professionals have all had to rapidly adapt to change. In some countries transplantation ground to a halt, raising a serious ethical dilemma in terms of which treatments should be prioritised—Cancer or Transplantation? As the pandemic progressed it became apparent that services within hospitals had to be rationalised due to redeployment of staff to cope with the overwhelming burden of treating those in desperate need. This chapter discusses the difficulties that are encountered until March of 2021 when trying to maintain a pancreas transplant service during a serious pandemic and some of the successful strategies that have been developed to help thwart such an unrelenting wave of despair.

Plastic crystal neopentyl glycol (NPG) displays a colossal barocaloric effect akin to conventional refrigerants, rendering it as a highly promising solid‐state refrigerant. However, its practical application is restricted by its elevated phase transition temperature, inferior thermal conductivity, and weak mechanical response. Herein, a molecular design strategy is employed, wherein NPG molecules are substituted with trimethylolpropane (TMP) molecules, resulting in the successful synthesis of novel plastic crystals, designated as NPG0.75TMP0.25, with a phase change temperature of 283.7 K. To enhance the thermal conductivity, a dual encapsulation strategy is utilized to fabricate a highly oriented thermally conductive hybrid network composed of NPG0.75TMP0.25 and expanded graphite (EG) by using melt adsorption and pressure induction. The hybrid networks also significantly augment the mechanical properties of NPG0.75TMP0.25. The resulting composite barocaloric material exhibits a maximum entropy change of 223.8 J K⁻¹ kg⁻¹ achieved under pressure changes below 40 MPa and a thermal conductivity of 18.31 W m⁻¹ K⁻¹. Moreover, the composite exhibits high mechanical response and fatigue resistance. This study not only demonstrates the potential of composite barocaloric materials for practical applications but also significantly advances the engineering of barocaloric refrigeration.

We report the first experimental and theoretical evaluation of the thermodynamic driving force for the reaction of metal–organic framework (MOF) materials with carbon dioxide, leading to a metal–organic carbonate phase. Carbonation upon exposure of MOFs to CO2 is a significant concern for the design and deployment of such materials in carbon storage technologies, and this work shows that the formation of a carbonate material from the popular SOD-topology framework material ZIF-8, as well as its dense-packed dia-topology polymorph, is significantly exothermic. With knowledge of the crystal structure of the starting and final phases in the carbonation reaction, we have also identified periodic density functional theory approaches that most closely reproduce the measured reaction enthalpies. This development now permits the use of advanced theoretical calculations to calculate the driving forces behind the carbonation of zeolitic imidazolate frameworks with reasonable accuracy.

Background Some patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) go on to experience post-COVID-19 condition or long COVID. Preliminary findings have given rise to the theory that long COVID may be due in part to a deranged immune response. In this study, we assess whether there is an association between SARS-CoV-2 infection and the incidence of immune-mediated inflammatory diseases (IMIDs). Methods Matched cohort study using primary care electronic health record data from the Clinical Practice Research Datalink Aurum database. The exposed cohort included 458,147 adults aged 18 years and older with a confirmed SARS-CoV-2 infection and no prior diagnosis of IMIDs. They were matched on age, sex, and general practice to 1,818,929 adults with no diagnosis of confirmed or suspected SARS-CoV-2 infection. The primary outcome was a composite of any of the following IMIDs: autoimmune thyroiditis, coeliac disease, inflammatory bowel disease (IBD), myasthenia gravis, pernicious anaemia, psoriasis, rheumatoid arthritis (RA), Sjogren’s syndrome, systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1DM), and vitiligo. The secondary outcomes were each of these conditions separately. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the primary and secondary outcomes, adjusting for age, sex, ethnic group, smoking status, body mass index, relevant infections, and medications. Results Six hundred and nighty six (0.15%) and 2230 (0.12%) patients in the exposed and unexposed cohort developed an IMID during the follow-up period over 0.29 person-years, giving a crude incidence rate of 4.59 and 3.65 per 1000 person-years, respectively. Patients in the exposed cohort had a 22% increased risk of developing an IMID, compared to the unexposed cohort (aHR 1.22, 95% CI 1.12 to 1.33). The incidence of three IMIDs was significantly associated with SARS-CoV-2 infection. These were T1DM (aHR 1.56, 1.09 to 2.23), IBD (aHR 1.36, 1.18 to 1.56), and psoriasis (1.23, 1.05 to 1.42). Conclusions SARS-CoV-2 was associated with an increased incidence of IMIDs including T1DM, IBD and psoriasis. However, these findings could be potentially due to ascertainment bias. Further research is needed to replicate these findings in other populations and to measure autoantibody profiles in cohorts of individuals with COVID-19.

BRAF mutations occur early in serrated colorectal cancers, but their long-term influence on tissue homeostasis is poorly characterized. We investigated the impact of short-term (3 days) and long-term (6 months) expression of BrafV600E in the intestinal tissue of an inducible mouse model. We show that BrafV600E perturbs the homeostasis of intestinal epithelial cells, with impaired differentiation of enterocytes emerging after prolonged expression of the oncogene. Moreover, BrafV600E leads to a persistent transcriptional reprogramming with enrichment of numerous gene signatures indicative of proliferation and tumorigenesis, and signatures suggestive of metabolic rewiring. We focused on the top-ranking cholesterol biosynthesis signature and confirmed its increased expression in human serrated lesions. Functionally, the cholesterol lowering drug atorvastatin prevents the establishment of intestinal crypt hyperplasia in BrafV600E-mutant mice. Overall, our work unveils the long-term impact of BrafV600E expression in intestinal tissue and suggests that colorectal cancers with mutations in BRAF might be prevented by statins.

The problem of model selection with a limited number of experimental trials has received considerable attention in cognitive science, where the role of experiments is to discriminate between theories expressed as computational models. Research on this subject has mostly been restricted to optimal experiment design with analytically tractable models. However, cognitive models of increasing complexity with intractable likelihoods are becoming more commonplace. In this paper, we propose BOSMOS, an approach to experimental design that can select between computational models without tractable likelihoods. It does so in a data-efficient manner by sequentially and adaptively generating informative experiments. In contrast to previous approaches, we introduce a novel simulator-based utility objective for design selection and a new approximation of the model likelihood for model selection. In simulated experiments, we demonstrate that the proposed BOSMOS technique can accurately select models in up to two orders of magnitude less time than existing LFI alternatives for three cognitive science tasks: memory retention, sequential signal detection, and risky choice.

Background The Safety Case is a regulatory technique that requires organisations to demonstrate to regulators that they have systematically identified hazards in their systems and reduced risks to being as low as reasonably practicable. It is used in several high-risk sectors, but only in a very limited way in healthcare. We examined the first documented attempt to apply the Safety Case methodology to clinical pathways. Methods Data are drawn from a mixed-methods evaluation of the Safer Clinical Systems programme. The development of a Safety Case for a defined clinical pathway was a centrepiece of the programme. We base our analysis on 143 interviews covering all aspects of the programme and on analysis of 13 Safety Cases produced by clinical teams. Results The principles behind a proactive, systematic approach to identifying and controlling risk that could be curated in a single document were broadly welcomed by participants, but was not straightforward to deliver. Compiling Safety Cases helped teams to identify safety hazards in clinical pathways, some of which had been previously occluded. However, the work of compiling Safety Cases was demanding of scarce skill and resource. Not all problems identified through proactive methods were tractable to the efforts of front-line staff. Some persistent hazards, originating from institutional and organisational vulnerabilities, appeared also to be out of the scope of control of even the board level of organisations. A particular dilemma for organisational senior leadership was whether to prioritise fixing the risks proactively identified in Safety Cases over other pressing issues, including those that had already resulted in harm. Conclusions The Safety Case approach was recognised by those involved in the Safer Clinical Systems programme as having potential value. However, it is also fraught with challenge, highlighting the limitations of efforts to transfer safety management practices to healthcare from other sectors.

In this article, we focus on relational labour as a form of emotional labour associated with the use of platformised possessions, such as pins, messages, photos, videos and playlists hosted on digital platforms, to maintain relationships with friends and family. We argue that this ongoing effort is a type of consumer labour because it generates profitable engagements for digital platforms, which intentionally exploit negative emotions, namely, anxiety and guilt, associated with maintaining social connections. Drawing on 47 depth interviews with people living in the South of the UK, we identify the direct (communication via platforms) and indirect (information gathered via platforms to attain relational goals) relational work undertaken by consumers via their platformised possessions. We then consider the emotional experiences related to this work, demonstrating how such experiences differ from reports of possession work on material goods, while maintaining platform profits. Recognising that this work is the basis of much platform engagement, and hence profit, we further show how this effort becomes a form of unpaid labour. We thus contribute to the nascent literature on platformisation and emotion, to broader studies of possession work, and to critical marketing scholarship on consumer labour.

Compressibility is a fundamental property of all materials. For fluids, i.e., gases and liquids, compressibility forms the basis of technologies such as pneumatics and hydraulics and determines basic phenomena such as the propagation of sound and shock waves. [ 2 ] In contrast to gases, liquids are almost incompressible. If the compressibility of liquids could be increased and controlled, new applications in hydraulics and shock absorption could result. Here, we show that dispersing hydrophobic porous particles into water gives aqueous suspensions with much greater compressibilities than any normal liquids such as water [ 3 ] (specifically, up to 20 times greater over certain pressure ranges). The increased compressibility results from water molecules being forced into the hydrophobic pores of the particles under applied pressure. The degree of compression can be controlled by varying the amount of porous particles added. Also, the pressure range of compression can be reduced by adding methanol or increased by adding salt. In all cases, the liquids expand back to their original volume when the applied pressure is released. The approach shown here is simple and economical and could potentially be scaled up to give large amounts of highly compressible liquids for the first time. This article is protected by copyright. All rights reserved

Cite this article: Needham DJ, Billingham J. 2023 The non-local Lotka-Volterra system with a top hat kernel-Part 1: Dynamics and steady states with small diffusivity. Proc. R. Soc. A 479: 20230381. We study the dynamics of the non-local Lotka-Volterra system u t = D u u xx + u(1 − φ * u − αv), v t = D v v xx + v(1 − φ * v − βu), where a star denotes the spatial convolution and the kernel φ is a top hat function. We initially focus on the case of small, equal diffusivities (D = D u = D v 1) together with weak interspecies interaction (α, β 1), and specifically α, β D. This can then be extended to consider small, but unequal, diffusivities and weak interactions, with now α, β D u , D v 1. Finally, we are able to develop the theory for the situation when the diffusivities remain small, but the interactions become stronger. In each case, we find that u and v independently develop into periodic spatial patterns that consist of separated humps on an O(1) time scale, and that these patterns become quasi-steady on a time scale proportional to the inverse diffusivity. These then interact on a longer time scale proportional to the inverse interaction scale, and approach a meta-stable state. Finally, a stable steady state is achieved on a much longer timescale, which is exponentially large relative to the preceding time scales. We are able to quantify this interaction process by determining a planar dynamical system that governs the temporal evolution of the separation between the two periodic arrays of humps on these sequentially algebraically and then exponentially long time scales. We find that,

There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.

We have produced a novel indium-based metallocycle complex (In-MeSH), which we initially observed as an unanticipated side-product in metal–organic framework (MOF) syntheses. The serendipitously synthesized metallocycle forms via the acid-catalysed decomposition of dimethyl sulfoxide (DMSO) during solvothermal reactions in the presence of indium nitrate, dimethylformamide and nitric acid. A search through the Cambridge Structural Database revealed isostructural zinc, ruthenium and palladium metallocycle complexes formed by other routes. The ruthenium analogue is catalytically active and the In-MeSH structure similarly displays accessible open metal sites around the outside of the ring. Furthermore, this study also gives access to the relatively uncommon oxidation state of In(II), the targeted synthesis of which can be challenging. In(II) complexes have been reported as having potentially important applications in areas such as catalytic water splitting.

Objective Post-extractive socket grafting techniques reduce alveolar ridge dimensional changes. Numerous graft materials have been suggested and a growing interest in tooth material has been observed as a valuable alternative to synthetic biomaterials or xenografts. Furthermore, different clinical procedures have been proposed for the wound closure of the post-extractive site. This study aims to compare histological and clinical outcomes of two different surgical techniques to seal the post-extractive site with the use of autologous demineralized extracted tooth as graft material. Materials and Methods Sixteen post-extractive socket without buccal and/or palatal bone walls, in sixteen healthy patients, were grafted with the autologous tooth material treated by the new Tooth Transformer device (Tooth Transformer, Milan, Italy). Alveolar socket preservation procedures were performed without flap elevation. Patients were randomly subdivided into two equal groups according to the site closure technique. In group A, the pedunculate tissue was used, while in group B ice cone technique. A bone samples were collected in each site after 4 months for histological analysis. Results No significant clinical differences among the different sealing techniques were observed. In both groups, the site was filled by new bone formation after 4 months of healing. The histological analysis revealed 46.1 ± 8.07% of bone volume, 9.2 ± 9.46% of residual graft, and 35.2 ± 12.36% of vital bone in group A, while group B shows 41.22 ± 5.88% of bone volume, 7.94 ± 7.54% of residual graft, and 31.7 ± 7.52% new bone. No statistical differences were detected ( p > 0.05). Conclusion Further studies with a large number of patients, and different observation periods will be needed to confirm the results of this pilot study; however, the interesting data obtained have shown how these techniques, mixed with the autologous dentin derived graft material, seem to promote bone regeneration and reduce physiological bone resorption during alveolar socket preservation treatments.

Background The critical role that middle managers play in enacting organisational culture change designed to address unprofessional co-worker behaviours has gone largely unexplored. We aimed to explore middle managers’ perspectives on i) whether they speak up when they or their team members experience unprofessional behaviours (UBs); ii) how concerns are handled; iii) the outcomes; and iv) the role of a professional accountability culture change program (known as Ethos) in driving change. Methods Qualitative, constructivist approach. Five metropolitan hospitals in Australia which had implemented Ethos. Purposive sampling was used to invite middle-level managers from medicine, nursing, and non-clinical support services. Semi-structured interviews conducted remotely. Inductive, reflexive thematic and descriptive thematic analyses undertaken using NVivo. Results Thirty interviews (approximately 60 min; August 2020 to May 2021): Nursing (n = 12), Support Services (n = 10), and Medical (n = 8) staff, working in public (n = 18) and private (n = 12) hospitals. One-third (n = 10) had a formal role in Ethos. All middle managers (hearers) had experienced the raising of UBs by their team (speakers). Themes representing reasons for ongoing UBs were: staying silent but active; history and hierarchy; and double-edged swords. The Ethos program was valued as a confidential, informal, non-punitive system but required improvements in profile and effectiveness. Participants described four response stages: i) determining if reports were genuine; ii) taking action depending on the speaker’s preference, behaviour factors (type, frequency, impact), if the person was known/unknown; iii) exploring for additional information; and iv) addressing either indirectly (e.g., change rosters) or directly (e.g., become a speaker). Conclusions Addressing UBs requires an organisational-level approach beyond supporting staff to speak up, to include those hearing and addressing UBs. We propose a new hearer’s model that details middle managers’ processes after a concern is raised, identifying where action can be taken to minimise avoidant behaviours to improve hospital culture, staff and patient safety.

The neurocranium is an integral part of the vertebrate head, itself a major evolutionary innovation1,2. However, its early history remains poorly understood, with great dissimilarity in form between the two living vertebrate groups: gnathostomes (jawed vertebrates) and cyclostomes (hagfishes and lampreys)2,3. The 100 Myr gap separating the Cambrian appearance of vertebrates4–6 from the earliest three-dimensionally preserved vertebrate neurocrania⁷ further obscures the origins of modern states. Here we use computed tomography to describe the cranial anatomy of an Ordovician stem-group gnathostome: Eriptychius americanus from the Harding Sandstone of Colorado, USA⁸. A fossilized head of Eriptychius preserves a symmetrical set of cartilages that we interpret as the preorbital neurocranium, enclosing the fronts of laterally placed orbits, terminally located mouth, olfactory bulbs and pineal organ. This suggests that, in the earliest gnathostomes, the neurocranium filled out the space between the dermal skeleton and brain, like in galeaspids, osteostracans and placoderms and unlike in cyclostomes². However, these cartilages are not fused into a single neurocranial unit, suggesting that this is a derived gnathostome trait. Eriptychius fills a major temporal and phylogenetic gap in our understanding of the evolution of the gnathostome head, revealing a neurocranium with an anatomy unlike that of any previously described vertebrate.

Mortality from alcohol-related liver disease (ALD) continues to rise and alcoholic hepatitis (AH) the acute inflammatory form of ALD is of particular concern. Severe AH is associated with a high short-term mortality (30% at 90 days, 50% at one-year) and in many cases infections are responsible for deaths. Given the link between alcohol, systemic inflammation and altered bone marrow haematopoesis, we investigated whether circulating red cell parameters may help in diagnoses of AH and provide prognostic information relating to disease severity, infection and survival outcomes. We used a Sysmex XN-1000 haematology instrument to analyse red cells in patients with AH(n=59), abstinent(n=32) and drinking (n=14) ALD compensated cirrhosis, decompensated alcoholic cirrhosis patients(n=39) and healthy controls(n=40). RCDW was compared with liver function tests and demographic features including mortality and infection risk. Our data confirmed that there was a reduction in circulating red cell count in AH but RCDW was elevated in AH and cirrhotic patients who were still actively drinking compared to the other groups. Longitudinal measurements suggested that values normalized over time in drinkers who were abstinent whilst under clinical investigation. 28 day and 1 year mortality was significantly reduced in AH patients with the highest RCDW and there was a significant correlation between GAHS and RCDW. We also noted a trend for increased risk of infection in patients with the highest RCDW but overall reported infectious complications in our unit were low as a result of prophylactic antibiotic prescribing. These findings are suggestive that the presence of acute inflammatory liver disease is associated with alterations in RCDW, and this should be investigated as a potential prognostic marker or indicator of infection risk in AH.

Background Physical frailty is associated with increased mortality in patients with end-stage liver disease (ESLD). Even though physical activity (PA) is recommended in ESLD, a lack of understanding of habitual patterns of PA (especially volume, intensity) and their relationship with physical frailty, limits healthcare professionals to generic NHS guidelines when prescribing PA for patients with ESLD. This prospective observational case-control study aimed to determine the association between physical frailty and the volume and intensity of PA in ESLD. Method Patients with ESLD were recruited from the liver transplant waiting list outpatient clinic (Birmingham, UK). Participants wore a GENEActiv® accelerometer watch device on their non-dominant wrist 24hrs/day for up to 14 days at home prior to the study visit. Patient characteristics (i.e. sex, age, disease type and severity) and the liver frailty index (LFI) were collated. The accelerometer data were analysed using R-package, GGIR (version 2.5–0). Average acceleration (PA volume), intensity gradient (spread of intensity participation over 24hrs) and minimum intensity for most active continuous time periods were calculated and compared across four quartiles of the LFI (1st ‘least frail’= <3.37, 2nd = 3.38–3.78, 3rd = 3.79–4.28, 4th ‘most frail’= >4.28). Results 43 participants with ESLD (65% male, mean age 54, UKELD 52, 51% ArLD, median LFI 3.59 [3.3–3.6]) were recruited. The volume of PA decreased as the degree of frailty increased, although this did not reach significance (p=0.08) (figure 1A). The intensity of PA significantly decreased as frailty increased (p=0.002), with the least frail achieving PA at significantly higher intensities than the most frail (mean difference 0.40, 95% CI 0.13 to 0.67, p= 0.004) (figure 1B). Those who were least frail were vigorously active for one continuous minute, while the most frail were only moderately active for one continuous minute. Participants with ESLD did not participate in moderate intensity PA for longer than two continuous minutes. • Download figure • Open in new tab • Download powerpoint Abstract O14 Figure 1 The association of (A) average acceleration and (B) intensity gradient on physical frailty, as measured by quartiles (1st [<3.37], 2nd [3.38–3.77], 3rd [3.78–4.28] and 4th [>4.28] of the Liver Frailty Index (LFI) Conclusion The intensity, rather than volume, of PA has the greatest association with the level of physical frailty in ESLD. Simple patient messages such as ‘when you move, move with intensity’ may be enough to improve physical frailty for patients with ESLD. Furthermore, consideration of short bursts (i.e. 2mins) of moderate intensity PA should be considered feasible in future protocols of PA for patients with ESLD.

Aims The aim of this study was to identify the optimal lip position for total hip arthroplasties (THAs) using a lipped liner. There is a lack of consensus on the optimal position, with substantial variability in surgeon practice. Methods A model of a THA was developed using a 20° lipped liner. Kinematic analyses included a physiological range of motion (ROM) analysis and a provocative dislocation manoeuvre analysis. ROM prior to impingement was calculated and, in impingement scenarios, the travel distance prior to dislocation was assessed. The combinations analyzed included nine cup positions (inclination 30-40-50°, anteversion 5-15-25°), three stem positions (anteversion 0-15-30°), and five lip orientations (right hip 7 to 11 o’clock). Results The position of the lip changes the ROM prior to impingement, with certain combinations leading to impingement within the physiological ROM. Inferior lip positions (7 to 8 o’clock) performed best with cup inclinations of 30° and 40°. Superior lip positions performed best with cup inclination of 50°. When impingement occurs in the plane of the lip, the lip increases the travel distance prior to dislocation. Inferior lip positions led to the largest increase in jump distance in a posterior dislocation provocation manoeuvre. Conclusion The lip orientation that provides optimal physiological ROM depends on the orientation of the cup and stem. For a THA with stem anteversion 15°, cup inclination 40°, and cup anteversion 15°, the optimal lip position was posterior-inferior (8 o’clock). Maximizing jump distance prior to dislocation while preventing impingement in the opposite direction is possible with appropriate lip positioning. Cite this article: Bone Joint Res 2023;12(9):571–579.