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Low-dose yellow fever vaccination in infants: a randomised, double-blind, non-inferiority trial
No full textBackground: The World Health Organization recommends fractional dose vaccination to address Yellow Fever (YF) vaccine shortages during outbreaks. In adults, a 500 IU dose has recently been shown to be non-inferior to the full standard dose, but the minimum dose for children is unknown.Methods: We conducted a randomised, double-blind, non-inferiority trial in Kenya and Uganda, involving infants aged 9–12 months old with no prior YF vaccination or infection. Participants were randomly assigned 1:1 in blocks of variable sizes of 4, 6 or 8 to receive either the standard dose (>13,000 IU) or 500 IU of the Institut Pasteur de Dakar 17D-204 YF vaccine, co-administered with measles-rubella (MR) vaccine. The primary outcome was seroconversion 28 days post-vaccination, defined as a four-fold or greater increase in antibody titre at day 28 from the baseline (day 0), as measured by the 50% plaque reduction neutralisation test (PRNT50). Non-inferiority was shown if the lower bound of the 95% confidence interval (CI) for the difference in seroconversion rates between doses exceeded −10 percentage points. This study is registered with ClinicalTrials.gov, NCT04059471.Findings: Between Oct 7, 2021, and Jun 14, 2023, 420 infants were enrolled and randomised (210 participants in each group). The seroconversion rate at day 28 was 99% (95% CI 96 to 100; 177 of 179 infants) for the standard dose and 93% (95% CI 88 to 96; 166 of 179 infants) for the 500 IU dose in the per-protocol population. The difference in seroconversion rate was −6.15 percentage points (95% CI −10.27 to −2.02). Twelve serious adverse events were reported in the study (8 in the 500 IU dose group and 4 in the standard dose group) but all were unrelated to vaccination.Interpretation: When compared to the full YF vaccine dose, a dose of 500 IU did not meet the noninferiority criterion suggesting that minimum dose requirements in adults are not generalisable to infants
An Archival Optical Counterpart Search for Extragalactic Fast X-Ray Transients Discovered by Einstein Probe
Get PDFExtragalactic fast X-ray transients (eFXTs) represent a rapidly growing class of high-energy phenomena, whose physical origins remain poorly understood. With its wide-field, sensitive all-sky monitoring, the Einstein Probe (EP) has greatly increased the discovery rate of eFXTs. The search for and identification of the optical counterparts of eFXTs are vital for understanding their classification and constraining their physical origin. Yet, a considerable fraction of eFXTs still lack secure classifications due to the absence of timely follow-up observations. We carry out a systematic search of publicly available optical survey data and transient databases (including the Zwicky Transient Facility and the Transient Name Server) for optical counterparts to eFXT candidates detected by EP. In this paper, we describe our ongoing program and report the first results. Specifically, we identified the eFXT EP240506a to be associated with a UV/optical counterpart, AT 2024ofs. Spectroscopy of its host galaxy with the Very Large Telescope yields a redshift of z = 0.120 ± 0.002. By combining archival survey data with early-time multiwavelength observations, we find that the luminosity and light-curve evolution of AT 2024ofs are consistent with a core-collapse supernova origin. From detectability simulations, we estimate a local event rate density ρ0=8.8−3.9+21.2yr−1Gpc−3 for EP240506a-like events, and completeness-corrected rate of about 36–78 yr−1 Gpc−3 for EP-detected X-ray transients associated with supernovae. Our results demonstrate the potential of EP to uncover prompt high-energy emission from core-collapse supernovae and underscore the critical importance of timely follow-up of future eFXT events
Violent and sexual victimisation and incident anxiety, mood and substance use disorders in childhood and adolescence: a co‐sibling study
Get PDFBackground: Studies on the association between victimisation in childhood and adolescence and psychiatric disorders increasingly acknowledge that these associations might be partly confounded by unmeasured familial factors. However, previous quasi‐experimental evidence is largely based on retrospective self‐reported data with potential response biases and small samples. Methods: We measured psychiatric disorders and victimisation events from routinely collected administrative datasets on Finnish total birth cohorts 1996–2005. We identified all violent and sexual victimisation events using plaintiff information taken from registers containing data on crimes reported to the police between birth and the end of 2020. Incident anxiety, mood and substance use disorders were identified from registers containing records of inpatient and specialised outpatient psychiatric care. We compared all those exposed to victimisation to five population controls and their unexposed siblings, with the latter thereby adjusting for shared unobserved familial factors. We used stratified Cox regression models to estimate the associations between victimisation and the psychiatric disorders, with a follow‐up from victimisation until the outcome, exit from the population or the end of 2020. Results: Violent and sexual police‐reported victimisation were both associated with an increased risk of psychiatric disorders, with adjusted hazard ratios ranging between 2.3 (95% Confidence Interval [CI]: 2.2, 2.4) for the association between violent victimisation and mood disorders and 3.9 (3.7, 4.1) for the association between sexual victimisation and anxiety disorders. In the sibling comparisons, the associations attenuated but remained clearly elevated, with the corresponding hazard ratios ranging between 1.9 (1.7, 2.1) and 2.6 (2.3, 2.9). Conclusions: The results are consistent with a causal interpretation of the association between police‐reported victimisation and psychiatric disorders. Mental health‐related support after victimisation is an important task as it may prevent the onset of psychiatric disorders. Prevention of victimisation might decrease the number of psychiatric disorders in the population
Determining the optimal management of geriatric type II odontoid fractures: a comparative network meta-analysis
Get PDFType II odontoid fractures are the most common cervical injury in geriatric populations, yet optimal management remains debated. This study compared the safety and effectiveness of non-surgical management (NSM), anterior dens screw (ADS) fixation, and posterior arthrodesis (PA) in these patients. A systematic review and frequentist network meta-analysis was conducted according to PRISMA-NMA guidelines. PubMed/MEDLINE, Embase, and CENTRAL were searched from inception to October 2025. Comparative studies including patients ≥ 60 years with Anderson-D’Alonzo type II fractures and reporting at least one primary outcome (mortality, union, stable non-union, unstable non-union) were eligible. Random-effects network models generated pooled odds ratios (ORs) with 95% confidence intervals (CIs). Nineteen studies involving 1242 patients were included (475 NSM; 340 ADS; 427 PA). Mortality did not differ among strategies. PA demonstrated the highest odds of union (OR 8.35, 95% CI 3.79–18.40 versus NSM), followed by ADS (OR 2.19, 95% CI 1.10–4.35 versus NSM). PA also outperformed ADS for fusion (OR 0.26, 95% CI 0.12–0.56). Stable non-union odds were similar across interventions, but unstable non-union was significantly more common after NSM (ADS versus NSM OR 5.93, 95% CI 1.33–26.35; PA versus NSM OR 13.55, 95% CI 2.50–73.36). Systemic morbidity was higher after both ADS (OR 1.87, 95% CI 1.02–3.44) and PA (OR 2.29, 95% CI 1.20–4.36) compared with NSM, while mechanical complications and secondary operation were uncommon and comparable. No global or local inconsistency was detected. In geriatric patients with type II odontoid fractures, PA provides the most reliable fusion and lowest unstable non-union risk, whereas NSM offers comparable survival with lower systemic morbidity but higher structural failure. ADS occupies an intermediate position, benefiting select anatomies where motion preservation or avoidance of prone surgical positioning is advantageous. Treatment should be individualized using a morphology-frailty framework that balances biomechanical stability against physiological reserve
Value coding by primate amygdala neurons complies with the continuity axiom of economic choice theory
Get PDFThe primate amygdala contributes to decision-making by encoding the subjective value of rewards, but whether these signals align with principles of economic theory remains unclear. Here, we tested compliance of amygdala value-coding with the continuity axiom of Expected Utility Theory (EUT), which posits a trade-off between reward probability and magnitude, in two male macaques. Given three ranked gambles, axiom-compliance was assessed via the monkeys' behavioral indifference between the intermediate gamble and a probabilistic combination of the other two. Choices reflected probability-magnitude integration to scalar subjective values consistent with the axiom. In a non-choice task, amygdala neurons showed graded responses to probability and magnitude cues that reflected these individual preferences, equalizing at subjective indifference. During choice, amygdala neurons directly integrated these value components and translated them into chosen-value and choice signals. These findings demonstrate that amygdala neurons represent behaviorally relevant, preference-based values in accordance with EUT's continuity axiom, and contribute to translating these values into economic decisions
Accelerating inference for multilayer neural networks with quantum computers
Get PDFFault-tolerant Quantum Processing Units (QPUs) promise to deliver exponential speed-ups in select computational tasks, yet their integration into modern deep learning pipelines remains unclear. In this work, we take a step towards bridging this gap by presenting the first fully-coherent quantum implementation of a multilayer neural network with non-linear activation functions. Our constructions mirror widely used deep learning architectures based on ResNet, and consist of residual blocks with multi-filter 2D convolutions, sigmoid activations, skip-connections, and layer normalizations. We analyse the complexity of inference for networks under three quantum data access regimes. Without any assumptions, we establish a quadratic speedup over classical methods for shallow bilinear-style networks. With efficient quantum access to the weights, we obtain a quartic speedup over classical methods. With efficient quantum access to both the inputs and the network weights, we prove that a network with an N-dimensional vectorized input, k residual block layers, and a final residual-linear-pooling layer can be implemented with an error of ϵ with O(polylog(N/ϵ) k ) inference cost
Pleural effusion in haematological malignancies: an educational position statement
Get PDFPleural effusion is a known complication of haematological malignancies, including lymphomas, leukaemias and multiple myeloma. The true overall incidence of pleural effusion in haematologic disorders is not precisely established, but case series suggest it occurs in roughly 20-48% of patients with these diseases. Among all malignant pleural effusions (MPEs), about 10-16% are attributable to haematologic cancers (especially lymphomas/leukaemias). The development of a pleural effusion in this context poses significant diagnostic challenges, as traditional tests such as pleural fluid cytology or pleural biopsy often have low diagnostic yield. Importantly, the underlying mechanisms of pleural effusion in haematological malignancy are diverse, ranging from direct pleural infiltration and mediastinal nodal obstruction to chylothorax, cardiac dysfunction, and treatment-related complications. These varied aetiologies not only complicate diagnosis but also have direct implications for both immediate and long-term management. Moreover, emerging evidence indicates that the presence of a pleural effusion in patients with haematological malignancies may reflect advanced disease or evolving complications and is often associated with a poorer prognosis. This position statement provides an overview of the prevalence, pathophysiology, diagnostic approach, management strategies, and prognosis of pleural effusions in haematological malignancies, and offers evidence-based recommendations to guide clinical practice
Two temperate Earth- and Neptune-sized planets orbiting fully convective M dwarfs
Get PDFAs the diversity of exoplanets continues to grow, it is important to revisit assumptions about habitability and classical habitable zone definitions. In this work, we introduce an expanded ‘temperate’ zone, defined by instellation fluxes in the range , thus encompassing a broader range of potentially habitable worlds. We also introduce the TEMPOS survey, which aims to produce a catalogue of precise radii for temperate planets orbiting M dwarfs with K. This work reports the discovery and characterization of two planets in this temperate regime orbiting mid-type M dwarfs: TOI-6716 b, a planet orbiting its M4 host star (, , ) with a period , and TOI-7384 b, a planet orbiting an M4 (, , ) star every . The radii of TOI-6716 b and TOI-7384 b have precisions of 6.8 per cent and 5.9 per cent, respectively. We validate these planets with multiband ground-based photometric observations, high-resolution imaging, and statistical analyses. We find these planets to have instellation fluxes close to the inner (hotter) edge of the temperate zone, with and for TOI-6716 b and TOI-7384 b, respectively. Also, with a predicted transmission spectroscopy metric similar to the TRAPPIST-1 planets, TOI-6716 b is likely to be a good rocky-world James Webb Space Telescope target, should it have retained its atmosphere