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Development of bivalent RBD adapted COVID-19 vaccines for broad sarbecovirus immunity
Get PDFCOVID-19 vaccine adaptation is critical to respond to continuously emerging SARS-CoV-2 variants with enhanced immune evasion. The ARVAC protein subunit vaccine, based on the receptor binding domain of the spike protein of SARS-CoV-2, has been adapted to XBB.1.5 and JN.1 variants, as monovalent and bivalent formulations. Preclinical studies in mice showed that ARVAC XBB.1.5 and JN.1 monovalent vaccines induced strong neutralizing antibodies against XBB and JN.1 lineages, though with limited efficacy against phylogenetically distant variants. By contrast, bivalent formulations combining Gamma antigen with either XBB.1.5 or JN.1 antigens demonstrated superior cross-neutralizing activity, covering variants from Ancestral to JN.1. Additionally, Gamma-containing bivalent vaccines elicited neutralizing antibodies against SARS-CoV-1, highlighting their potential for broad-spectrum immunity. Cellular immune studies confirmed robust CD4+ T cell activation across all formulations. These findings support the continued adaptation of ARVAC to current circulant variants and propose ARVAC bivalent vaccines containing the Gamma antigen as a strategy for induction of pan-sarbecovirus immunity
Pulmonary hypertension aetiologies in different parts of the world
Get PDFPulmonary hypertension is a serious condition characterised by elevated blood pressure in the pulmonary arteries, caused by various aetiologies and via different pathological processes. Over the past seventy years, our understanding and management of this disorder have greatly improved, resulting in increased diagnosis and effective clinical management. Current epidemiological estimates are challenged by the increased awareness of this condition and the changing definitions and classification systems. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has also shown temporal changes in the epidemiology of pulmonary hypertension over the last thirty years, contributing to regional variations in prevalence and incidence. This review explores the complexities of global and regional variations in different types of pulmonary hypertension reported through many registries, databases and regional studies. Although these tools can help estimate prevalence and incidences, they may also underestimate the actual number of cases due to the continuously changing understanding of the condition and increase awareness globally. Therefore, continued research, international collaboration, and standardised data collection are essential for achieving a more accurate global view of pulmonary hypertension and developing effective management strategies for this serious condition that significantly impacts general health
The effects of L2 exposure at school on the cognitive development of children from monolingual backgrounds: a longitudinal study
No full textThis longitudinal study examined the cognitive development of Spanish children from monolingual backgrounds attending schools with varying levels of English exposure (13%-83%), to assess whether higher L2 exposure results in advantages over time. 229 children (ages 6-7) completed background (non-verbal reasoning, working memory, L1 vocabulary, L2 vocabulary) and experimental tests measuring attentional/executive functions (selective attention, divided attention, switching, inhibition) at the beginning and end of Year 1 of Primary Education. Generalized linear mixed-effects models, accounting for factors such as family educational level, onset of L2 exposure, and language exposure outside of school, indicated that children’s cognitive skills benefit from (high) L2 exposure at school, with greater L2 exposure being linked to more enhanced attentional/executive skills as well as to a larger L2 vocabulary. These findings support the positive effects of immersion programs, suggesting that L2 exposure in school settings alone can contribute to more developed attentional/executive skills
Towards high-speed Swept Source Optical Coherence Tomography
Get PDFOptical coherence tomography (OCT) has evolved into an impactful biomedical imaging modality, with swept-source OCT (SS-OCT) emerging as a key technology for pushing axial scan rates from hundreds of Hz to tens of MHz. However, achieving these high speeds introduces critical challenges: (i) developing light sources capable of emitting stable multi-MHz sweeps, (ii) scaling lateral scanners to match axial speeds, and (iii) enabling real-time processing with digitizers exceeding tens of GSa/s. Resolving these limitations is imperative, as high-speed OCT unlocks transformative applications-from capturing dynamic processes to reducing motion artifacts in clinical imaging and enabling large-volume diagnostics. Advancements in this area promise to expand OCT's role in functional imaging, intraoperative guidance, and high-throughput screening, bridging the gap between laboratory innovation and real-world clinical impact.
At first, it remains hard to produce swept sources that are able to sweep at multi-MHz; for that, a sweep modality that is able to cope with high rates such as time stretch has been investigated in this thesis to overcome the issues above. A commercially available Erbium-doped amplifier is transformed into a mode-locked laser by nonlinear polarization rotation, which seeds a dispersion compensation fibre, stretching the pulse duration to nearly 200 ns. The OCT capabilities of the source are tested, and the main imaging parameters, such as axial resolution, range and drop-off, are characterized. Secondly, a 40 MHz swept source laser based on time-stretch after a supercontinuum is used along with an electro-optic deflector, a potassium tantalum niobate (KTN) crystal, producing a system that was able to capture volumes at 400 Hz. However, the processing to obtain the OCT images is not done in real-time. As such, in the final part of this thesis, alternative processing algorithms are explored to generate real-time in-vivo images of the retina and cornea; i) through numerical procedures, a novel FDML laser at 850 nm is used at 828 kHz with bidirectional sweeping. For the first time, an FMDL laser has been integrated with complex master-slave (CMS) systems; the laser has been fully characterized and enables real-time B-Scans and \textit{en-face} imaging of the human retina. ii) A MEMS-VCSEL swept source centred at 1060 nm working at 1.6 MHz is used in a downconversion scheme where two interferometers are used, and the high frequencies generated in the measuring interferometer are mixed with a reference signal to downconvert the signal to lower frequencies and alleviate the requirements needed for a high sampling rate digitiser. The main similarities and differences between the numerical processing methods and analogue methods are given. Finally, \textit{en-face} OCT images of the retina with the downconversion scheme are presented
More than presence-absence; modelling (e)DNA concentration across time and space from qPCR survey data
Get PDFEnvironmental DNA (eDNA) surveys offer a revolutionary approach to species monitoring by detecting DNA traces left by organisms in environmental samples, such as water and soil. These surveys provide a cost-effective, non-invasive, and highly sensitive alternative to traditional methods that rely on direct observation of species, especially for protected or invasive species. Quantitative PCR (qPCR) is a technique used to amplify and quantify a targeted DNA molecule, making it a popular tool for monitoring focal species. Modelling of qPCR data has so far focused on inferring species presence/absence at surveyed sites. However, qPCR output is also informative regarding DNA concentration of the species in the sample, and hence, with the appropriate modelling approach, in the environment. In this paper, we introduce a modelling framework that infers DNA concentration at surveyed sites across time and space, and as a function of covariates, from qPCR output. Our approach accounts for contamination and inhibition in lab analyses, addressing biases particularly notable at low DNA concentrations, and for the inherent stochasticity in the corresponding data. Additionally, we incorporate heteroscedasticity in qPCR output, recognizing the increased variance of qPCR data at lower DNA concentrations. We validate our model through a simulation study, comparing its performance against models that ignore contamination/inhibition and variance heterogeneity. Further, we apply the model to three case studies involving aquatic and semi-aquatic species surveys in the UK. Our findings demonstrate improved accuracy and robustness in estimating DNA concentrations, offering a refined tool for ecological monitoring and conservation efforts
Thanaleisure and the super-rich: the case of the Titan submersible disaster
Get PDFThis commentary reflects on the Titan submersible disaster as a case study of the thanatic leisure habits of the super-rich. Previous analyses of elite consumption have explored their tendency to seek out exclusivity and luxury, and to monopolise space (Thurlow and Jaworski 2012; Featherstone 2014; Atkinson 2021). Drawing on literature from the fields of thanatourism and dark leisure, the commentary theorises how deep sea submersible tourism offers adjacency to death and suffering as a means to pursue mythical masculine desires, confront artificial frontiers and hardships, and assert status. It concludes with a discussion of how the wastefulness, pollution and redemption struggles that characterise what is here defined as thanaleisure add to our understanding of thanacapitalism (Korstanje 2016). That is, as an economic system that not only commodifies death and suffering, but justifies its own existence through promoting the hypermobility of the few at the expense of the majority
Magnetic and magnetocaloric properties of the two-dimensional Ln2(phthalate)3(H2O) (Ln = Gd-Dy) framework series
Get PDFThe magnetic properties of a series of layered, two-dimensional Ln2(phth)3(H2O) materials (where Ln = Gd-Dy and phth = phthalate) metal–organic framework (MOF) materials have been examined to evaluate their potential as magnetocaloric materials. The Gd2(phth)3(H2O) material was found to exhibit the best performance of the series with a −ΔSmmax of 16.3 J kg−1 K−1 for a magnetic field change of 5–0 T. Although modest compared to other Gd-based magnetocaloric frameworks, this material was notable for exhibiting its peak entropy change at 4 K. This contrasts with the majority of Gd-based magnetocaloric materials whose performance is usually optimised at 2 K (or lower) and found to rapidly decrease with increasing temperature and is attributed to the stronger magnetic interactions present in this material
Rescue epilepsy medication and training: A comparison between midazolam use, guidelines, clinical practice, and possibilities in the UK and Norway
Get PDFObjectives: Status epilepticus (SE) is a prolonged epileptic seizure carrying significant risk of long‐term disability and death. Rescue therapies are prescribed for prehospital administration to terminate SE. This study compared prescribing practices of rescue therapies of midazolam in the UK and Norway. Methods: A cross‐sectional, online, 21‐item Likert‐style survey was administered to epilepsy professionals in the UK circulated via ILAE/ESNA and in Norway via ILAE/Epilepsinet using a non‐discriminatory exponential snowballing technique leading to non‐probability sampling. Data were collected anonymously and analyzed using descriptive statistics, Mann–Whitney, Chi‐square, and Fisher's exact tests. Significance was accepted at p < 0.05. Results: All 86 UK and 53 Norway respondents identified buccal midazolam as the first‐line rescue medication choice in the community for prolonged and/or generalized tonic–clonic seizures. Norwegian respondents had significantly more experience in epilepsy‐related work (p = 0.002), were more likely to have a larger caseload on buccal midazolam (p < 0.001), prescribed higher midazolam doses (p < 0.001), and provided training yearly (p < 0.001). UK respondents were more likely to delegate rescue medication prescribing to primary care (p = 0.006) and reviewed emergency management plans more frequently (p = 0.006). There was an inter‐country difference in the period of midazolam non‐use that respondents required before withdrawing from treatment plans (p < 0.001). Concern about inappropriate use of buccal midazolam was similarly high in both countries. Significance: This study compared epilepsy professionals in two neighboring high‐income countries. Findings suggest an urgent need for international guidelines to recommend best practices on prescribing doses and withdrawal of buccal midazolam. The potential abuse of buccal midazolam by patients and carers warrants further investigation. Plain Language Summary: This study investigated doctors' and nurses' views on the use of epilepsy rescue therapies, particularly midazolam. These are medications that can stop dangerously long epileptic seizures from progressing to the point of serious injury or death. The study was carried out in both the UK and Norway to establish differences between the countries. The key findings were that Norwegian doctors prescribed rescue medications at a higher dose, that UK clinicians reviewed and deprescribed medications faster after patients stopped having prolonged seizures, and that clinicians in both countries were concerned about medications being misused or abused by patients and carers
Stand-Up in the United Kingdom
No full textThis chapter uses a performance by Stewart Lee as a way in to trace the history of stand-up comedy in the UK from music hall, through variety theatre, working men's clubs, alternative comedy to today's stand-up scene, including Black British stand-up. It analyses the work of a number of British comedians, including Dan Leno, Suzette Tarri, Max Miller, Alexei Sayle, Pauline Melville, Tony Allen, Mo Gilligan and Josie Long
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