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Longitudinal analysis of neutralizing antibodies against SARS-CoV-1 and different SARS-CoV-2 strains in breakthrough and unvaccinated COVID-19 patients in Thailand (2021-2022)
Get PDFThe emergence of SARS-CoV-2 variants that evade immune responses poses challenges to effective prevention. We prospectively enrolled 111 COVID-19 patients in Thailand (2021-2022), who received homologous or heterologous vaccines or were unvaccinated. Plasma neutralizing antibody (nAb) levels against SARS-CoV-1 and 13 SARS-CoV-2 strains were measured using a multiplex surrogate virus neutralization test (sVNT) assay within a year. nAb levels increased in two weeks, showing strong inhibition against ancestral SARS-CoV-2 and non-omicron variants, but not against SAR-CoV-1 and lower responses to omicron variants. nAb levels declined by the day 60. Breakthrough patients with heterologous vaccines had higher nAb levels compared to other groups. nAb levels were lower in breakthrough patients with pneumonia than those with other conditions. Notably, breakthrough patients aged ≥60 showed rapid declines in antibody levels. Our findings highlight diverse immune responses influenced by immunization, age, and clinical conditions, underscoring the need for tailored vaccination strategies against evolving variants
A Cool Earth-sized Planet Candidate Transiting a Tenth Magnitude K-dwarf From K2
Get PDFThe transit method is currently one of our best means for the detection of potentially habitable “Earth-like” exoplanets. In principle, given sufficiently high photometric precision, cool Earth-sized exoplanets orbiting Sun-like stars could be discovered via single transit detections; however, this has not previously been achieved. In this work, we report a 10 hr long single transit event which occurred on the V = 10.1 K-dwarf HD 137010 during K2 Campaign 15 in 2017. This transit is comparatively shallow (225 ± 10 ppm) but is detected at high signal-to-noise thanks to the exceptionally high photometric precision achieved for the target. Our analysis of the K2 photometry, historical and new imaging observations, and archival radial velocities and astrometry strongly indicate that the event was astrophysical, occurred on-target, and can be best explained by a transiting planet candidate, which we designate HD 137010 b. The single observed transit implies a radius of 1.06−0.05+0.06R⊕ , and assuming negligible orbital eccentricity we estimate an orbital period of 355−59+200 days ( a=0.88−0.10+0.32 au), properties comparable to Earth. We project an incident flux of 0.29−0.13+0.11I⊕ , which would place HD 137010 b near the outer edge of the habitable zone. This is the first planet candidate with Earth-like radius and orbital properties transiting a Sun-like star bright enough for substantial follow-up observations
Revisiting uncertainty estimation and calibration of large language models
No full textAs large language models (LLMs) are increasingly deployed in high-stakes applications, robust uncertainty estimation is essential for ensuring the safe and trustworthy deployment of LLMs. We present the most comprehensive study to date of uncertainty estimation in LLMs, evaluating 80 models spanning open- and closed-source families, dense and Mixture-of-Experts (MoE) architectures, reasoning and nonreasoning modes, quantization variants and parameter scales from 0.6B to 671B. Focusing on three representative black-box single-pass methods, including token probability-based uncertainty (TPU), numerical verbal uncertainty (NVU), and linguistic verbal uncertainty (LVU), we systematically evaluate uncertainty calibration and selective classification using the challenging MMLU-Pro benchmark, which covers both reasoning-intensive and knowledge-based tasks. Our results show that LVU consistently outperforms TPU and NVU, offering stronger calibration and discrimination while being more interpretable. We also find that high accuracy does not imply reliable uncertainty, and that model scale, post-training, reasoning ability and quantization all influence estimation performance. Notably, LLMs exhibit better uncertainty estimates on reasoning tasks than on knowledge-heavy ones, and good calibration does not necessarily translate to effective error ranking. These findings highlight the need for multi-perspective evaluation and position LVU as a practical tool for improving the reliability of LLMs in real-world settings
Structural and spectroscopic studies of metal ions and metal clusters with small molecules
Get PDFGas-phase metal clusters and metal ion–ligand complexes exhibit a diverse array of structural motifs and size-dependent properties. These systems serve as valuable model platforms for exploring fundamental chemical bonding and reactivity at the molecular level. Detailed studies of such isolated clusters provide bottom-up insights into processes relevant to heterogeneous catalysis and materials chemistry, including but not limited to molecular activation at metal centres. This thesis presents experimental and computational studies on the structure and physical properties of different cluster systems of interest, as well as development work that has been completed to produce gas-phase metal clusters.Following a general introduction to the field and methods section which details the techniques that have been used to complete the studies, the experimental sections are presented in three parts. Part A presents infrared photodissociation (IRPD) studies on metal ion-ligand complexes; with Chapter 3 presenting work on cationic nitrosyl complexes, [M(NO)n] +, of Group 9 elements (Co, Rh, Ir), and Chapter 4 focusing on platinum and platinum oxide nitrosyl complexes, [PtOx(NO)n] + (x = 0, 1). In Chapter 3, spectroscopic and computational evidence suggested that (NO)2 dimer moieties form when nitric oxide (NO) molecules bind non-covalently with other molecules that are bound directly to the metal cation centre. These dimer moieties only form following the first coordination shell for these complexes being filled with nitric oxide molecules, with the number of molecules in the first shell being dependent on the metal. In Chapter 4, it was shown that up to six ligands could bind to the platinum centre in the first coordination shell before dimer moieties form. With the oxygen-rich platinum complexes, evidence of the formation of an N2O3 moiety, formed from an NO and an NO2 molecule, is presented; this is illustrated by the appearance of intense spectral features between 1900 − 2000 cm−1 in the IRPD spectra which are consistent with previous studies on [NO2(NO)n] + clusters.Part B describes infrared studies on metal clusters using free-electron laser (FEL) light. Chapter 5 describes photoionisation studies of neutral tantalum and tantalum oxide clusters, TanOx, performed using the FELICE free-electron laser at the HFML-FELIX facility in Nijmegen, The Netherlands. Preliminary calculations on cationic Ta clusters, and their reactions with nitrogen oxides (NO/N2O) are shown; with dissociative binding being predicted for all cluster sizes. In the experiment, size-dependent thermionic emission was observed with the neutral clusters, with odd-even alternations in signal intensity being caused by the clusters swapping between having open- and closed-shell electronic configurations. Ta-O stretches in the range 650 − 750 cm−1 are also observed and are in close agreement with previous studies on cationic tantalum oxide clusters. The structures of the tantalum oxide clusters that contribute towards the experimental spectra are determined using quantum chemical calculations; with the dioxide clusters shown to contain two distinct oxygen atoms, rather than molecularly bound O2 molecules.Part C focuses on in-house development work that has been completed to build and test a new cluster source. Chapter 6 presents designs, simulations, and experimental studies on an experimental setup used to characterise a new bimetallic laser ablation cluster source. Photoionisation of nitric oxide was used to determine the shape of the gas pulse generated by the new source when different configurations and conditions were used; the shape of the pulse was then compared with predictions made using a simple kinetic theory model. Subsequently, neutral and cationic gold clusters, Au0/+ n , were generated and studied using the custom built time-of-flight mass spectrometer. The source will be used in the future on existing experiments within the Mackenzie Group to investigate the role of cluster size and composition on reactivity with small molecules
Perturbations of whole-brain model reveal critical areas related to relapse of early psychosis
Get PDFOvercoming an initial psychotic episode does not always lead to recovery; relapses and subsequent psychotic episodes may happen afterward. Even if the characterization of psychotic disorders can be related to alterations in brain connectivity, clear identification of the brain areas for relapse is missing. Here, we leverage on whole-brain modeling linking anatomical structural information with functional activity as measured by MRI in 196 participants. Patients were classified into Stage II (first episode), IIIa (incomplete remission), IIIb (remission followed by one relapse), and IIIc (remission followed by several relapses), depending on the course of psychosis up to the time of the brain scan. From these data, a low-dimensional manifold reduction of the brain dynamics was obtained using deep learning variational autoencoders in which the different stages are represented, and a classification model can be trained to distinguish them. Then, a dimensionality analysis was performed to find the optimal dimension that allows the distinction between first episode and relapsing cases with high accuracy. Finally, perturbations were introduced in the model to reveal the brain regions associated with the absence of relapse, which could help predict which brain regions to target during therapy and assist the treatment of patients suffering from psychotic disorders
Temperature‐Dependent Lithium Migration and Increased Thermal Stability Within Palladium Nanoparticles
Get PDFThe incorporation of light‐element dopants into monometallic nanoparticle catalysts enables precise modulation of their electronic structures, thereby tailoring catalytic performance. However, despite the widespread use and general understanding of such systems, fundamental aspects of dopant–framework interactions and solid‐solution behavior in light‐element‐doped metal nanoparticles remain incompletely characterized. Here, using a one‐step synthesis of lithiated palladium (Pd) nanoparticles formed by an in situ lithiation process with lithium (Li) acetate, we investigate the temperature‐dependent phase behavior of the Pd–Li solid solution by variable‐temperature synchrotron powder X‐ray diffraction (VT‐SPXRD). In situ thermal Bragg diffraction studies reveal unexpected delithiation dynamics and phase complexity in the metastable PdLi intermetallic compound, including previously unreported temperature‐dependent lithium migration and site‐occupancy redistribution. Remarkably, we demonstrate that interstitial lithium doping enhances thermal stability from 150 °C to over 400 °C, with higher lithium loadings (0.5–1.5 eq) maintaining structural integrity up to 515 °C. This unexpected stabilization, attributed to nanoparticle encapsulation effects, provides fundamental insight into light‐element doping mechanisms in metallic nanoparticles and paves the way for the rational design of electronically tuned nanocatalysts
Differential motor signatures in isolated and narcolepsy-related REM sleep behaviour disorder: a preliminary study
Get PDFBackground: REM sleep behaviour disorder (RBD) is a prodrome of α-synucleinopathy, yet mechanistic pathways are unresolved. Narcolepsy type 1 with RBD (NT1-RBD) provides a human model of orexin deficiency. We tested whether REM motor semiology differs categorically between isolated RBD (iRBD) and NT1-RBD. Methods: We retrospectively analyzed blinded video-polysomnographic scorings from 57 patients (iRBD n = 34; NT1-RBD n = 23). Across 857 REM events (iRBD 717; NT1-RBD 140), we classified topography (head/neck, trunk, upper, lower limbs), complexity (elementary vs. complex), content (scenic, violent, self-referential), vocal/orofacial features, spatial distribution and laterality using a pre-specified codebook. The patient was the primary unit of inference. Binary features used Fisher’s exact tests with Cohen’s h; the per-patient complex-event proportion used Mann–Whitney and Cliff’s δ (bootstrap 95% CI). Robustness checks comprised Beta-Binomial posteriors (Beta [1,1]) and patient-label permutation tests (10,000 permutations). Results: REM motor phenotypes diverged categorically. Lower-limb dominance occurred in 18/23 (78.3%) NT1-RBD vs. 7/34 (20.6%) iRBD (Fisher p < 0.0001; Cohen’s h ≈ +1.23), whereas upper-limb dominance occurred in 24/34 (70.6%) iRBD vs. 2/23 (8.7%) NT1-RBD (p < 0.0001; h ≈ −1.40). Any complex event was present in 27/34 (79.4%) iRBD vs. 3/23 (13.0%) NT1-RBD (p < 0.0001; h ≈ −1.46); violent enactments in 16/34 (47.1%) vs. 0/23 (0%) (p < 0.0001; h ≈ −1.51). The per-patient complex-event proportion was higher in iRBD [median 0.21 (0.05–0.33)] than NT1-RBD [0.00 (0.00–0.00)] (Mann–Whitney p < 0.0001; Cliff’s δ = −0.665; 95% CI −0.853 to −0.441). Event-level summaries were concordant; permutation p-values were 0.0001 for upper-limb involvement and 0.0083 for complex behaviour. Conclusion: iRBD and NT1-RBD exhibit qualitatively distinct REM motor phenotypes: upper-body-dominant, complex/scenic behaviours in iRBD versus elementary, predominantly bilateral lower-limb behaviours with notable trunk recruitment in NT1-RBD, supported by large effect sizes and convergent robustness checks. These findings motivate mechanistic studies of hypothalamic-brainstem-cortical integration in REM and suggest that semiological profiling may aid stratification in prodromal neurodegeneration
The role of media in PISA 2022 mathematics education policymaking in Anglophone countries
No full textAs governments react to international rankings, the Organisation for Economic Cooperation and Development’s Programme for International Student Assessment (PISA) of 15-year-old students has arguably influenced many governments’ mathematics education policies. In this paper, we look at the relationship between the latest cycle of PISA, policymaking and media in the economies where English is an official or substantial working language (Anglophone countries). We analysed three sources of media responses to PISA 2022 results, from governments, mainstream media, and social media, focusing on the number of the reactions, the sentiment of the reactions, and some relevant themes pertaining to PISA 2022 mathematics coverage. The results show that the PISA results have been used and discussed differently by different governments and that media responses seem to relate to pertinent policy objectives. Our contribution sheds light on how the PISA 2022 results interact with policymaking for mathematics education in Anglophone countries
Motivation for learning Chinese compared to European languages: an exploration in English Secondary schools
No full textThere is little published research on school-aged learners of Mandarin Chinese in anglophone contexts. This article explores English secondary school pupils' motivation for learning Chinese compared to European languages. The research questions were: (1) What is the strength and nature of pupils' self-reported motivation for learning languages? (2) How does pupils' motivation for learning Chinese compare with their motivation for learning European languages? Focus groups were conducted with 43 pupils (aged 11–12) in their first year at five state-funded secondary schools. In all languages, culture and a desire to connect with speakers were strong motivators; classroom experiences were also key, underlining teachers' central role. Motivation for Chinese was frequently linked to novelty, difference, challenge, and enjoyment of the character-based writing system. The article highlights practical classroom implications, particularly the need for teachers to consider the motivational impact of pedagogical decisions relating to curriculum content, task design, and classroom organization
Five rules for scientifically-credible nature markets
No full textNature markets are proliferating rapidly around the world, yet it is underacknowledged that they have been practiced in various forms for decades. A large body of scientific research has shown that nature markets regularly do not achieve their environmental objectives, and provides generalisable lessons to support their ongoing improvement. The scale of the biodiversity crisis and the enduring popularity of nature markets means it is now critical to stop reproducing the same mistakes. Here we synthesise international research from the history of nature markets and summarise five rules which are necessary precursors for achieving their environmental aims. We propose a checklist for investors, policymakers, and civil society to assess whether nature markets are likely to be delivering scientifically-credible outcomes. We score the world’s largest nature markets against these rules and show all face integrity risks. Lastly, we outline critical evidence-based actions that can be taken to push nature markets towards greater integrity