324139 research outputs found
Sort by
Health-economic impacts of age- and sex-targeted Lassa fever vaccination in endemic regions of Nigeria, Guinea, Liberia and Sierra Leone: a modelling study
No full textBackground: Lassa fever is an emerging zoonotic disease endemic to west Africa. Several vaccines aimed at preventing Lassa fever are currently under development, creating a need to assess how best to administer them once licensed for human use. We aimed to project the health-economic burden of Lassa fever from 2025 to 2037 across age and sex groups in subnational administrative divisions of west Africa with endemic Lassa mammarenavirus transmission and to estimate the cost-effectiveness of targeting Lassa vaccination to different risk groups.
Methods: In this vaccine-impact modelling study, we developed a mathematical model using a zoonosis risk map and epidemiological data from recent and ongoing cohort studies to predict the health-economic burden of Lassa fever across age and sex groups in endemic regions. We simulated vaccination campaigns targeting different risk groups to estimate the cost-effectiveness of various strategies for Lassa vaccine administration. Threshold vaccine costs (TVCs), which represent the break-even price per dose of vaccine administered, were estimated in international dollars (INT$ 2023), accounting for health-care costs, productivity losses, and monetised disability-adjusted life-years (DALYs) averted by vaccination.
Findings: Lassa fever was estimated to cause 6·23 (95% uncertainty interval (UI) 4·21–8·42) hospitalisations, 0·75 (0·48–1·10) deaths and 31·1 (17·7–52·2) DALYs per 100 000 person-years. Vaccine strategies targeting adolescents–adults aged 15–49, older adults aged 50 years and older, and women of childbearing age (WCBA) aged 15–49 years prevented, respectively, the most hospitalisations, deaths, and DALYs per 100 000 vaccine doses. Under base case assumptions, the most cost-effective strategy (greatest net monetary benefit) was untargeted vaccination for a vaccine costing intl dollar2 per dose, and targeting adolescents–adults at intl dollar5 per dose. At intl dollar10 per dose or more, none of the considered strategies were cost-effective. The highest TVC for a single-dose vaccine was estimated at intl dollar7·39 (95% UI 4·33–11·60) when targeting adolescents–adults, followed by intl dollar6·69 (4·17–9·85) when targeting older adults, intl dollar6·10 (3·56–9·74) when targeting WCBA, and intl dollar1·94 (1·10–3·10) when targeting children.
Interpretation: Targeting of adolescents–adults appears to generate the greatest health-economic value per vaccine dose. However, the most cost-effective vaccination strategy will depend on vaccine price
Journal of Bone and Mineral Research (JBMR) 40th anniversary celebration: the second decade (part 1)
No full textMagnetic ordering in moiré graphene multilayers from a continuum Hartree+ U approach
Get PDFRecently, symmetry-broken ground states, such as correlated insulating states, magnetic order and superconductivity, have been discovered in twisted bilayer graphene (tBLG) and twisted trilayer graphene (tTLG) near the so-called magic angles. Understanding the magnetic order in these systems is challenging, however, as atomistic methods become extremely expensive near the magic angle and continuum approaches fail to capture important atomistic details. In this work, we develop an approach to incorporate short-ranged Hubbard interactions self-consistently in a continuum model. In addition, we include long-ranged Coulomb interactions which are known to be important when doping the flat bands of tBLG and tTLG. Therefore, for the first time, magnetic order in moiré graphene multilayers is self-consistently explored in a continuum model with atomistic detail. With this approach, we perform a systematic analysis of the magnetic phase diagram of tBLG as a function of doping level and twist angle, near the magic angle. Our results are consistent with previous perturbative atomistic Hartree+U calculations. Furthermore, we investigated magnetic order of tTLG, which were found to be similar to those in tBLG. In the future, the developed continuum model can be utilized to investigate magnetic ordering tendencies from short-range exchange interactions in other moiré graphene multilayers as a function of doping, twist angle, screening environment, among other variables
Curing the brain: in search for new astrocyte-specific therapies
No full textAstroglia, an extended class of homeostatic and defensive cells of the central nervous system, contribute to the pathogenesis of all known neurological and neuropsychiatric disorders. Pathophysiology of astrocytes is complex, mutable, disease and disease-stage specific. In neuroinflammatory lesions and in various chronic conditions astrocytes undergo an evolutionary conserved defensive remodelling known as reactive astrogliosis, which produces highly heterogeneous reactive astrocytic phenotypes. Broadly, reactive astrogliosis can be classified into proliferative anysomorphic barrier-forming astrogliosis characteristic of traumatic CNS lesions and non-proliferative isomorphic gliosis widely manifested in chronic neuropathologies. In addition, in many pathologies astrocytes undergo atrophy and asthenia with resulting loss of homeostatic support and neuroprotection precipitating neuronal damage. Reactive and atrophic astrocytes may co-exist or emerge in sequence in a disease-stage-dependent manner. Several classes of astrocyte-specific molecules and processes implicated in various diseases of the CNS represent therapeutic targets. Astrocyte-specific therapeutic strategies may improve both disease-preventing and disease-modifying therapeutic outcomes
Scaling of overall cooling effectiveness of HPT NGVs from conventional laboratory conditions to engine conditions
Get PDFThe increased use of engine-realistic test vehicles in turbomachinery research has contributed to practical and academic interest in a robust validated theory for the scaling of overall cooling effectiveness (θ) from conventional laboratory conditions to engine conditions. The purpose of this thesis is to quantify and explain the effect of moving from conventional laboratory conditions to engine conditions on θ, via theoretical considerations and experimental validation.
In chapter 2, the impact of temperature ratio on overall cooling effectiveness is quantified using a bespoke conjugate low-order solver. The network model consists of a single row of film cooling holes; a near-wall mixing region; internal cooling channels in both the leading circuit and trailing-edge (TE) circuit; a diabatic external wall; and an adiabatic internal wall. The geometry of the model is representative of real-engine high-pressure turbine (HPT) nozzle guide vanes (NGVs). For the near-wall mixing region, the film effectiveness distribution at the reference temperature ratio (TR) is modelled using a conventional correlation from literature and scaled to non-reference TR by using an entrainment-based mixing model (assumption of fully-mixed flow). Conventional correlations from literature are used to model external and internal heat transfer coefficients, and coolant pressure loss in the internal cooling channels. The streamwise distributions of these parameters may deviate—slightly—from those of real-engine HPT NGVs, however using representative correlations from literature ensures that the model captures the relevant physics for accurately predicting changes in θ with TR for real-engine HPT NGVs. When subject to specific boundary conditions (BCs), the system is solved by considering energy and mass conservation arguments, and geometrical constraints on the system. Three different internal cooling system networks and two domain-global BCs (the macro BCs on the implied NGV row) are considered. It is shown that θ decreases with reducing TR and that the magnitude of the change is insensitive to the internal cooling system architecture; the type of domain-global BC imposed; and the surface-averaged value of overall cooling effectiveness at the reference TR. It is shown that there are significant scaling effects associated with absolute temperature and mainstream gas properties and that the result is highly sensitive to the particular definition of θ. The work presented in this chapter is the subject of a published journal paper [1].
In chapter 3, the theory for scaling of overall cooling effectiveness with temperature ratio (discussed in chapter 2) is independently applied to a fourth cooling system. This system consists of three rows of film cooling holes; diabatic external and internal walls; and conducting webs connecting the external and internal wall. Low-order-model predictions show that θ decreases with reducing TR, however the magnitude of the change is significantly smaller than that predicted for the three systems above. It is shown that this is due to the presence of the conducting webs. The low-order-model-predicted results are experimentally validated by conducting experiments in a high-temperature flat-plate test facility. The work presented in this chapter is the subject of an upcoming journal paper, which is currently under review [2].
In chapter 4, the theory for scaling of overall cooling effectiveness with TR is experimentally validated by conducting experiments in the ECAT+ facility using real-engine HPT NGVs. ECAT+ is a new second-generation engine-realistic test vehicle at the University of Oxford that allows testing at engine-realistic conditions of Reynolds number (Re), Mach number (M), coolant-to-mainstream pressure ratio (CMPR), turbulence intensity (Tu) and TR. The general experimental results are broadly in agreement with the low-order-model predictions for the four NGV-representative cooling systems discussed in chapters 2 and 3. The work presented in this chapter is the subject of a complete draft of an upcoming journal paper [3].
It is hoped that the theoretical and experimental results reported in this thesis will be useful to other researchers when scaling their experimental results to engine conditions
Mendelssohn's Lobgesang: the genesis of the symphony-cantata and a critical edition of its original version
No full textMendelssohn's Symphony no. 2, the Lobgesang Symphony, was first performed on 25 June 1840. However, he was not satisfied with the original composition and made significant alterations in the autograph manuscript before releasing it for publication. The symphony is known today in its 1841 second version. A critical edition, based on the copyist Eduard Henschke' s copy of Mendelssohn's original score, has been prepared of the discarded, and for decades lost, original version. The edition and critical notes make up volume II. As background and preamble to the edition, a narrative in five broad sections, contained in volume I, puts the work into context. Chapter 1 gives an account of the historical background to the symphony, the Gutenberg Festival, which brought about its composition, and early performances. The compositional development of the work is the subject of Chapter 2 focussing on the creation of a new genre - the symphony-cantata. This includes renewed speculation as to whether the symphony dates back to an otherwise lost symphony in B flat of 1838. Chapter 3 provides an introduction to the sources - their whereabouts, physical appearance and importance - as a prelude to Chapter 4, a physical unravelling of Mendelssohn's autograph score with its layers of revisions, paste-overs, page insertions and deletions. A critical comparison of the two versions, made possible by the availability of the Henschke score, provides the first clear insight into the compositional process of the Lobgesang, and an opportunity to discuss the major structural alterations made to the first version and why they were made. Chapter 5 draws together conclusions from the earlier chapters focusing on the unusual nature of the musical form and textual content, and to what extent Mendelssohn achieved his aims, using his background as a point of reference in determining what some of those were. The thesis concludes that these aims were continually developing through each stage of the compositional process as he hit upon new ideas, seemingly by accident, until he finally created the symphony-cantata
Ring‐Width Dendrochronology, Isotopic Dendrochronology and Radiocarbon Dating of Timbers From the Spire Scaffold of Salisbury Cathedral, Wiltshire, England
Get PDFTen timbers from the spire scaffold of Salisbury Cathedral were dated using a combination of ring‐width dendrochronology, stable oxygen isotopic dendrochronology and radiocarbon dating. Seven timbers were coeval and assigned a combined empirical felling date range of 1352–1378, which was further refined to 1351–1359 (OxCal 95.4%). These results would indicate that the scaffold was not a 1320s construction but instead built later in the 14th century. The remaining sampled timbers produced a precise felling date of spring 1737 and are coincident with documented repair work in 1738
Extreme Neutral Outflow in a Non-active Galactic Nucleus Quiescent Galaxy at z ∼ 1.3
Get PDFWe report the discovery of a substantial sodium doublet (Na D λλ5890, 5896)—traced neutral outflow in the quiescent galaxy JADES-GS-206183 at z = 1.317. Its JWST/NIRSpec-Microshutter Array spectrum shows a deep, blueshifted Na D absorption, revealing a neutral outflow with vout=828−49+79kms−1 and a mass outflow rate of log(Ṁout/M⊙yr−1)=2.40−0.16+0.11 . This outflow rate exceeds that of any neutral outflows identified beyond z ∼ 1 by the same line and is comparable with those in local galaxies with intensive star formation (SF) or luminous active galactic nuclei (AGN). JADES-GS-206183 is also a peculiar quiescent galaxy with a spiral+bar morphology, high dust attenuation (AV = 2.27 ± 0.23 mag). Paschen α (Paα) emission from the FRESCO NIRCam grism confirms its low star formation rate (SFRPaα = 10.78 ± 0.55 M⊙ yr−1), placing it 0.5 dex below the main sequence ( log(sSFRyr−1)=−10.2 ). Despite the systematics introduced by different SF history priors, the spectral energy distribution modeling, combining Hubble Space Telescope-to-NIRCam photometry with the Very Large Telescope/MUSE spectrum, suggests that JADES-GS-206183 experienced an older episode of SF 0.5–2 Gyr ago and a possible rejuvenation within the recent ∼10 Myr. Moreover, rest-frame optical lines indicate that the current AGN activity of JADES-GS-206183, if present, is also weak. Even though we tentatively detect a broad component of the Hα line, it likely traces an ionized outflow rather than an AGN. The results demonstrate that the Na D outflow in JADES-GS-206183 is highly unlikely to be driven by current SF or nuclear activity. Instead, it may represent a long-lasting fossil outflow from past AGN activity, potentially cotriggered with the early phase of rejuvenation
Tislelizumab efficacy and safety compared to other anti–PD-1s: a network meta-analysis of first-line therapies for unresectable, locally advanced or metastatic esophageal squamous cell carcinoma
Get PDFIntroduction: The addition of programmed cell death protein-1 (PD-1) inhibitors to chemotherapy (CT) or anti-CTLA4 (ipilimumab) has recently emerged as an effective first-line (1L) treatment for esophageal squamous cell carcinoma (ESCC), the most common form of esophageal cancer globally. Methods: A systematic literature review (SLR) was conducted to identify randomized controlled trials (RCTs) investigating 1L PD-1 inhibitor regimens in adult patients with unresectable, locally advanced, or metastatic ESCC. Bayesian NMAs were conducted to evaluate overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade ≥3 treatment-related adverse events (TRAEs). Results: Three eligible RCTs were identified, evaluating three PD-1 inhibitor regimens with broad regulatory approval for 1L ESCC in combination with CT (tislelizumab, nivolumab, and pembrolizumab). Tislelizumab + CT demonstrated similar long-term OS to nivolumab + CT and pembrolizumab + CT but a significant PFS benefit over nivolumab + CT and comparable efficacy to pembrolizumab + CT. Subgroup analyses were consistent with the base case, including among patients with varying PD-L1 expression (≥1% and ≥5% Tumor Area Positivity [TAP] score or ≥1 and ≥5 combined positive score [CPS]), Asia versus the rest of world, and different underlying CT backbones. Safety profiles were comparable across the three treatments. Conclusion: Tislelizumab + CT is an effective 1L treatment option for advanced or metastatic ESCC, demonstrating comparable efficacy and safety outcomes relative to existing treatments
Roll‐to‐Roll Manufacturing of Flexible Thermoelectric Semiconductors Using Low‐Level Direct‐Current Sputtering
Get PDFDirect‐current (DC) sputtering combined with roll‐to‐roll processing offers a highly competitive approach for scaling up the manufacturing of flexible functional thin films. However, its application to less‐conductive functional materials, such as semiconductors, remains limited due to charge buildup and arcing on the target. This study investigates the intrinsic relationships between DC sputtering power and the surface topography, elemental composition, crystallography, and thermoelectric properties of flexible thin‐film semiconductors. We explore low‐level DC power for room‐temperature roll‐to‐roll sputtering of Bi‐Te thermoelectric films, identifying an optimal power window that avoids charge‐buildup effects on the semiconductor target. Low‐power DC sputtering enables controlled crystallographic, microstructural, and compositional characteristics, thereby modulating electrical transport properties and, consequently, thermoelectric performance. As a result, a room‐temperature figure of merit of ∼0.1 is achieved at an optimal power of 0.22 kW while maintaining high‐throughput roll‐to‐roll manufacturability. Device‐level validation is demonstrated using a flexible thermoelectric generator, showing output performance consistent with COMSOL simulations