Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.

Zircon U-Pb geochronology, geochemistry and Hf isotope analysis of supracrustal rocks in the Anshan-Benxi area in the northeastern part of the North China Craton can help constrain their petrogenesis and tectonic background, providing evidence for a further investigation of the late Neoarchaean tectonic environment in the Anshan-Benxi area. The primary rock types observed among the supracrustal rocks in the Anshan-Benxi area comprise amphibolite, metamorphic rhyolite, metamorphic sandstone, chlorite schist, actinolite schist, among others. SHRIMP zircon U-Pb dating indicates that magmatic zircons from the amphibolite (GCN-1) formed at 2553 ± 18Ma. Similarly, LA-ICP-MS zircon U-Pb dating reveals that magmatic zircons from the metamorphic rhyolite (G2304-1) were formed at 2457 ± 35Ma. The peak age of the metamorphic sandstone is determined to be approximately 2500Ma, suggesting that the supracrustal rocks in the Anshan-Benxi area originated in the late Neoarchaean. The protoliths of sericite quartz schist and metamorphic rhyolite are identified as rhyolitic volcanic rocks, displaying a right-leaning distribution pattern of rare earth elements (REEs). On the other hand, actinolite schist, chlorite schist and amphibolite are classified as basaltic volcanic rocks, exhibiting a flat REE pattern with a weak negative Eu anomaly. The εHf(t) value of metamorphic rhyolite ranges between -1.19 and -1.47, with a two- stage depleted mantle model age of tDM2(Ma) = 2922–3132 Ma. The protolith magma of sericite quartz schist and metamorphic rhyolite originates from partial melting of 3.0Ga basaltic crust, while the source of actinolite schist, chlorite schist and amphibolite are mainly derived from the mantle. In summary, the findings suggest that plate already existed in the late Neoarchaean or earlier, with magmatism in the Anshan-Benxi area likely occurring within an arc tectonic environment linked to plate subduction.

Melting and solidification in periodically time-modulated thermal convection are relevant for numerous natural and engineering systems, for example, glacial melting under periodic sun radiation and latent thermal energy storage under periodically pulsating heating. It is highly relevant for the estimation of melt rate and melt efficiency management. However, even the dynamics of a solid–liquid interface shape subjected to a simple sinusoidal heating has not yet been investigated in detail. In this paper, we offer a better understanding of the modulation frequency dependence of the melting and solidification front. We numerically investigate periodic melting and solidification in turbulent convective flow with the solid above and the melted liquid below, and sinusoidal heating at the bottom plate with the mean temperature equal to the melting temperature. We investigate how the periodic heating can prevent the full solidification, and the resulting flow structures and the quasi-equilibrium interface height. We further study the dependence on the heating modulation frequency. As the frequency decreases, we found two distinct regimes, which are ‘partially solid’ and ‘fully solid’. In the fully solid regime, the liquid freezes completely, and the effect of the modulation is limited. In the partially solid regime, the solid partially melts, and a steady or unsteady solid–liquid interface forms depending on the frequency. The interface height can be derived based on the energy balance through the interface. In the partially solid regime, the interface height oscillates periodically, following the frequency of modulation. Here, we propose a perturbation approach that can predict the dependency of the oscillation amplitude on the modulation frequency.

In confined multi-obstacle environments, generating feasible paths for continuum robots is challenging due to the need to avoid obstacles while considering the kinematic limitations of the robot. This paper deals with the path-planning algorithm for continuum robots in confined multi-obstacle environments to prevent their over-deformation. By modifying the tree expansion process of the Rapidly-exploring Random Tree Star (RRT*) algorithm, a path-planning algorithm called the continuum-RRT* algorithm herein is proposed to achieve fewer iterations and faster convergence as well as generating desired paths that adhere to the kinematic limitations of the continuum robots. Then path planning and path tracking are implemented on a tendon-driven four-section continuum robot to validate the effectiveness of the path-planning algorithm. The path-planning results show that the path generated by the algorithm indeed has fewer transitions, and the path generated by the algorithm is closer to the optimal path that satisfies the kinematic limitations of the continuum robot. Furthermore, path-tracking experiments validate the successful navigation of the continuum robot along the algorithm-generated path, exhibiting an error range of 2.51%–3.91%. This attests to the effectiveness of the proposed algorithm in meeting the navigation requirements of continuum robots.

Integrons are important genetic elements that allow easy acquisition and dissemination of antimicrobial resistance genes. Studies reporting occurrence of integrons in Staphylococcus aureus (S. aureus) isolated from bovine mastitis in large dairy farms across China are scarce. The aim of this study was to investigate the occurrence of class 1 integrons (intI1), antimicrobial resistance (AMR) and associated genes in S. aureus isolated from bovine mastitis and their associations. Minimum inhibitory concentrations (MICs) were determined to evaluate the AMR phenotypes, whereas PCR was carried out to assess the occurrence of AMR genes and intI1. In addition, index cluster analysis was used to estimate associations between AMR phenotype, genotype and intI1 in 103 isolates. Overall, 83% of S. aureus were intI1-positive and 5 types of gene cassettes were detected. Susceptibility against single antimicrobial agents ranged from 0% (erythromycin), 12% (ampicillin) and 16% (penicillin G) to 96% (gentamicin). Most isolates (64%) were intermediate-resistant against erythromycin, whereas resistance against ceftriaxone (22%), clindamycin (4%), cefotaxime (2%), tetracycline (1%) and ciprofloxacin (1%) were relatively uncommon. The predominant resistant gene was blaZ gene (n = 88, 85%) followed by tetD gene (n = 85, 83%). With an estimated prevalence of 12% of the mecA gene, methicillin-resistant S. aureus isolates had higher MIC50 and MIC90 for majority of antimicrobials than methicillin-susceptible S. aureus isolates. Presence of the ermC gene was associated with erythromycin resistance. Ampicillin, erythromycin and penicillin G resistance were associated with intI1. The data presented in our study indicated that class 1 integron-mediated resistance possibly plays an important role in dissemination of AMR in S. aureus isolated from bovine mastitis.

For dissolving active oil droplets in an ambient liquid, it is generally assumed that the Marangoni effect results in repulsive interactions, while the buoyancy effects caused by the density difference between the droplets, diffusing product and the ambient fluid are usually neglected. However, it has been observed in recent experiments that active droplets can form clusters due to buoyancy-driven convection (Krüger et al., Eur. Phys. J. E, vol. 39, 2016, pp. 1–9). In this study we numerically analyse the buoyancy effect, in addition to the propulsion caused by Marangoni flow (with its strength characterized by the Péclet number $Pe$). The buoyancy effects have their origin in (i) the density difference between the droplet and the ambient liquid, which is characterized by the Galileo number $Ga$; and (ii) the density difference between the diffusing product (i.e. filled micelles) and the ambient liquid, which can be quantified by a solutal Rayleigh number $Ra$. We analyse how the attracting and repulsing behaviour of neighbouring droplets depends on the control parameters $Pe$, $Ga$ and $Ra$. We find that while the Marangoni effect leads to the well-known repulsion between the interacting droplets, the buoyancy effect of the reaction product leads to buoyancy-driven attraction. At sufficiently large $Ra$, even collisions between the droplets can take place. Our study on the effect of $Ga$ further shows that with increasing $Ga$, the collision becomes delayed. Moreover, we derive that the attracting velocity of the droplets, which is characterized by a Reynolds number $Re_d$, is proportional to $Ra^{1/4}/( \ell /R)$, where $\ell /R$ is the distance between the neighbouring droplets normalized by the droplet radius. Finally, we numerically obtain the repulsive velocity of the droplets, characterized by a Reynolds number $Re_{rep}$, which is proportional to $PeRa^{-0.38}$. The balance of attractive and repulsive effect leads to $Pe\sim Ra^{0.63}$, which agrees well with the transition curve between the regimes with and without collision.

Aiming to identify the complexing mechanisms of heavy metal cations on edge surfaces of 2:1-type clay minerals, systemic first-principles molecular dynamics (FPMD) simulations were conducted and the microscopic structures and complex free energies were obtained. Taking Cd(II) as a model cation, the structures on both (010) and (110) edges of the complexes were derived for the three possible binding sites (≡SiO, ≡Al(OH)2/≡AlOH≡AlSiO, and vacant sites). The stable complexes adsorbed on the three binding sites on both terminations had similar structures. The free energies of the complexes on (010) edges were calculated by using the constrained FPMD method. The free energies of complexes on the ≡SiO and ≡Al(OH)2 sites were similar and they were both significantly lower than the free energy of the complex on the octahedral vacant site. In association with the concept of high energy site (HES) and low energy site (LES) in the 2 Site Protolysis Non Electrostatic Surface Complexation and Cation Exchange (2SPNE SC/CE) sorption model, the vacant site was assigned to HES and the other two sites to LES, respectively.

Danon disease is a rare X-linked disorder caused by deficiency of the lysosome-associated membrane protein-2. We report a case of hypertrophic obstructive cardiomyopathy secondary to a novel mutation in the lysosome-associated membrane protein-2 gene in a 10-year-old male adolescent. We performed a modified extended Morrow procedure to minimise the risk of death and improve the patient’s quality of life. The patient did not have exertional dyspnoea, and auscultation did not reveal a cardiac murmur at 1-year follow-up.

Mental ill health is more common among juvenile offenders relative to adolescents in general. Little is known about individual differences in their long-term psychological adaptation and its predictors from multiple aspects of their life. This study aims to identify heterogeneous trajectories of probable psychiatric conditions and their predictors. Participants included 574 juvenile offenders who were first convicted for serious crimes and without detention history. The participants were assessed at 11 timepoints over seven years (2000–2010). Growth mixture modeling revealed the same three trajectories for both probable anxiety and probable depression: stable low trajectory (75.96%; 75.78%), stable high trajectory (15.16%; 10.98%), and recovery (8.89%, 13.24%). Least absolute shrinkage and selection operator (LASSO) logistic regression identified three multilevel predictors for memberships of different trajectories. Risk factors against stable low trajectory lay within personal (e.g., neuroticism), relationship (e.g., parental hostility), and contextual levels (e.g., chaotic neighborhood). Resilience factors for stable low trajectory included strong work orientation and low education level of father. Recovery was predicted by Black race, self-identity, high education level of father, and nonincarcerated sentencing. Our findings suggest that both psychopathology and psychological resilience could be predicted by multiple personal, relationship, and contextual factors in the social ecology of juvenile offenders.

The development of high-brightness X-ray free electron lasers (XFELs), such as hard X-ray self-seeding free electron lasers and XFEL oscillators (XFELOs), brings a severe challenge to the crystal monochromator due to a strong non-uniform thermal load. The distortion caused by spatial temperature gradients can severely affect the optical performance of crystals. Therefore, this paper presents a model to estimate the performance of non-uniform thermally distorted crystals. The model not only takes into account thermal strain, slope error and incident angle deviation, but also considers temperature-dependent factors such as the Debye–Waller factor and electric susceptibility. Our investigation indicates that the Debye–Waller factor reduces the height and bandwidth of rocking curves, and the impact of the electric susceptibility is tiny. The proposed model can describe the distortion of the reflectivity and transmissivity curves of non-uniform thermally loaded crystals and can be applied in the design of crystal monochromators, crystal splitters, crystal compressors and XFELOs.

The 4H-SiC crystal is found to have great potential in terahertz generation via nonlinear optical frequency conversion due to its extremely high optical damage threshold, wide transparent range, etc. In this paper, optical rectification (OR) with tilted-pulse-front (TPF) setting based on the 4H-SiC crystal is proposed. The theory accounts for the optimization of incident pulse pre-chirping in the TPF OR process under high-intensity femtosecond laser pumping. Compared with the currently recognized LiNbO3-based TPF OR, which generates a single-cycle terahertz pulse within 3 THz, 4H-SiC demonstrates a significant advantage in producing ultra-widely tunable (up to over 14 THz, TPF angle 31°–38°) terahertz waves with high efficiency (~10–2) and strong field (~MV/cm). Besides, the spectrum characteristics, as well as the evolution from single- to multi-cycle terahertz pulses can be modulated flexibly by pre-chirping. The simulation results show that 4H-SiC enables terahertz frequency extending to an unprecedent range by OR, which has extremely important potential in strong-field terahertz applications.

To contribute to the treatment decision and optimize coagulase-negative staphylococcus (CNS) control programs, we conducted a meta-analysis to investigate the epidemiology and antimicrobial resistance rates of coagulase-negative staphylococcus associated with bovine mastitis in China. Three databases (PubMed, Google scholar and China National Knowledge Infrastructure database) were utilized to obtain relevant publications. A total of 18 publications were included in our research, and 3 of them included antimicrobial resistant (AMR) test. The pooled prevalence of coagulase-negative staphylococcus was 17.28%. Subgroup analysis revealed that the prevalence was higher in South China than in North China, was higher in 2011–2020 than in 2000–2010 and was higher in clinical bovine mastitis cases than in subclinical cases. The pooled AMR were most resistant to β-lactams, followed by tetracyclines, quinolones, nitrofurans, lincosamides, sulfonamides, amphenicol and aminoglycosides. The pooled AMR rate of coagulase-negative staphylococcus was lower in 2011–2020 than in 2000–2010. Although the prevalence of CNS showed an increasing trend over 20 years, the AMR rate showed a decreasing trend, and the clinical type of mastitis was the most frequent and the prevalence was highest in South China. Finally, CNS was most resistant to β-lactams amongst the eight groups of antimicrobial agents.

This study is designed to explore the association between dietary betaine intake and risk of all-cause and cardiovascular death in patients with coronary artery diseases (CAD). In this cohort study, 1292 patients with CAD were followed up for a median of 9·2 years. Baseline dietary betaine intake was collected using a paper-based semi-quantitative FFQ and assessed according to the US Department of Agriculture (USDA) database and the data of betaine in common foods. Cox proportional hazards regression models were used to analyse the association between dietary betaine intake and risks of all-cause and cardiovascular mortality. During the follow-up periods, 259 deaths recorded in 1292 participants, of which 167 died of CVD. Patients in the highest tertile of dietary betaine intake had a lower risk of all-cause (P = 0·007) and cardiovascular death (P < 0·001) than those in the lowest tertile after adjusting for age and sex, traditional cardiovascular risk factors and other potential confounders. After further adjusting for plasma methionine metabolites and vitamins, hazard ratio across tertiles of dietary betaine intake were 1·00, 0·84 and 0·72 for all-cause mortality (P for trend = 0·124), and 1·00, 0·77 and 0·55 for cardiovascular mortality (P for trend = 0·021). Higher dietary betaine intake was associated with a decreased risk of cardiovascular death after fully adjustment for cardiovascular risk factors, other potential confounders and plasma methionine metabolites and vitamins. However, the association between dietary betaine intake and risk of all-cause mortality was not statistically significant after further adjusting for plasma methionine metabolites and vitamins.

In the treatment of infertile patients with non-obstructive azoospermia (NOA) caused by the deletion of the azoospermia factor c region (AZFc) on the Y chromosome, synchronous and asynchronous surgical strategies are discussed. Clinical data from NOA patients with the AZFc deletion who underwent micro-TESE were analyzed retrospectively. The sperm retrieval rate (SRR) and sperm utilization rate of synchronous and asynchronous operation groups were followed up and compared. The fertilization rate, high-quality embryo rate, clinical pregnancy rate, abortion rate, and cumulative live birth rate of ICSI in patients with successful sperm retrieval were compared between the two groups. The two groups had sperm utilization rates of 98.9% (93/94) and 50.0% (14/28), respectively. The asynchronous group’s sperm consumption rates were much lower than those of the synchronous operation group. Fertilization rate, high-quality embryo rate, clinical pregnancy rate of fresh transfer cycle, abortion rate, and cumulative live birth rate of patients in the synchronous operation group with fresh sperm, and the asynchronous operation group with thawed sperm, respectively, were 30.6% vs 33.8%, 33.8% vs 40.7%, 40.0% vs 12.5%, 30.4% vs 7.1%. Between the two groups, there was no significant difference. This suggests that individuals with NOA caused by the AZFc deletion have a high possibility of successfully acquiring sperm using micro-TESE and ICSI to conceive their own offspring. Synchronous micro-TESE is recommended to improve sperm utilization rate and the cumulative live birth rate.