| 1. |
- Micah, Angela E., et al.
(författare)
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Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
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Forskningsöversikt (refereegranskat)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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| 2. |
- Santoro, V., et al.
(författare)
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HighNESS conceptual design report: Volume I
- 2024
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Ingår i: Journal of Neutron Research. - 1023-8166 .- 1477-2655. ; 25:3-4, s. 85-314
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Tidskriftsartikel (refereegranskat)abstract
- The European Spallation Source, currently under construction in Lund, Sweden, is a multidisciplinary international laboratory. Once completed to full specifications, it will operate the world’s most powerful pulsed neutron source. Supported by a 3 million Euro Research and Innovation Action within the EU Horizon 2020 program, a design study (HighNESS) has been completed to develop a second neutron source located below the spallation target. Compared to the first source, designed for high cold and thermal brightness, the new source has been optimized to deliver higher intensity, and a shift to longer wavelengths in the spectral regions of cold (CN, 2–20 Å), very cold (VCN, 10–120 Å), and ultracold (UCN, >500 Å) neutrons. The second source comprises a large liquid deuterium moderator designed to produce CN and support secondary VCN and UCN sources. Various options have been explored in the proposed designs, aiming for world-leading performance in neutronics. These designs will enable the development of several new instrument concepts and facilitate the implementation of a high-sensitivity neutron-antineutron oscillation experiment (NNBAR). This document serves as the Conceptual Design Report for the HighNESS project, representing its final deliverable.
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| 3. |
- Santoro, V., et al.
(författare)
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HighNESS conceptual design report: Volume II. the NNBAR experiment.
- 2024
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Ingår i: Journal of Neutron Research. - 1023-8166 .- 1477-2655. ; 25:3-4, s. 315-406
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Tidskriftsartikel (refereegranskat)abstract
- A key aim of the HighNESS project for the European Spallation Source is to enable cutting-edge particle physics experiments. This volume presents a conceptual design report for the NNBAR experiment. NNBAR would exploit a new cold lower moderator to make the first search in over thirty years for free neutrons converting to anti-neutrons. The observation of such a baryon-number-violating signature would be of fundamental significance and tackle open questions in modern physics, including the origin of the matter-antimatter asymmetry. This report shows the design of the beamline, supermirror focusing system, magnetic and radiation shielding, and anti-neutron detector necessary for the experiment. A range of simulation programs are employed to quantify the performance of the experiment and show how background can be suppressed. For a search with full background suppression, a sensitivity improvement of three orders of magnitude is expected, as compared with the previous search. Civil engineering studies for the NNBAR beamline are also shown, as is a costing model for the experiment.
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| 4. |
- Huang, Tao, et al.
(författare)
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Dairy Consumption and Body Mass Index Among Adults : Mendelian Randomization Analysis of 184802 Individuals from 25 Studies
- 2018
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 64:1, s. 183-191
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined.METHODS: We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT-13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies.RESULTS: Higher dairy intake was associated with higher BMI (β = 0.03 kg/m2 per serving/day; 95% CI, 0.00–0.06; P = 0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14–0.25) serving/day higher dairy intake (P = 3.15 × 10−12) and 0.12 (95% CI, 0.06–0.17) kg/m2 higher BMI (P = 2.11 × 10−5). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m2 per serving/day; 95% CI, 0.27–0.92; P = 3.0 × 10−4).CONCLUSIONS: The present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.
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| 5. |
- Backman, Filip, 1991-, et al.
(författare)
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The development of the NNBAR experiment
- 2022
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Ingår i: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- The NNBAR experiment for the European Spallation Source will search for free neutrons converting to antineutrons with a sensitivity improvement of three orders of magnitude compared to the last such search. This paper describes progress towards a conceptual design report for NNBAR. The design of a moderator, neutron reflector, beamline, shielding and annihilation detector is reported. The simulations used form part of a model which will be used for optimisation of the experiment design and quantification of its sensitivity.
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| 6. |
- Dian, E., et al.
(författare)
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Preparation for activation measurements of concrete and PE-B4C-concrete to be applied for shielding at the European Spallation Source
- 2018
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Ingår i: 22nd Meeting of the International Collaboration on Advanced Neutron Sources (ICANS XXII). - : Institute of Physics Publishing (IOPP).
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Konferensbidrag (refereegranskat)abstract
- To improve the effect of the concrete below 10 MeV where iron has resonances in the cross section, a new concrete have been developed. The PE-B4C-concrete utilizes hydrogen containing PE to thermalize the neutron and boron for in situ absorption. It is of utmost importance that the activation of the shielding material itself is well-understood, since it is planned to be used at the ESS. The first steps in this direction are shown the present study, in which concrete as well as reference aluminium samples are subject to XRF measurements to precisely determine the element content. This is compared to data sheets from the vender, and simulations are carried out to predict the sample activity. The samples are planned for insertion into the the Budapest Research Reactor, followed be activity and spectral measurements.
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| 7. |
- Santoro, V., et al.
(författare)
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DEVELOPMENT OF A HIGH INTENSITY NEUTRON SOURCE AT THE EUROPEAN SPALLATION SOURCE : THE HIGHNESS PROJECT
- 2022
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Ingår i: Proceedings of the 14th International Topical Meeting on Nuclear Applications of Accelerators, AccApp 2021, Embedded with the 2021 ANS Winter Meeting. - 9780894487842 ; , s. 11-20
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Konferensbidrag (refereegranskat)abstract
- The European Spallation Source (ESS), presently under construction in Lund, Sweden, is a multidisciplinary international laboratory that will operate the world’s most powerful pulsed neutron source. Supported by a 3M Euro Research and Innovation Action within the EU Horizon 2020 program, a design study (HighNESS) is now underway to develop a second neutron source below the spallation target. Compared to the first source, located above the spallation target and designed for high cold and thermal brightness, the new source will provide higher intensity, and a shift to longer wavelengths in the spectral regions of cold (2-20 Å), very cold (VCN, 10-120 Å), and ultra cold (UCN, > 500 Å) neutrons. The core of the second source will consist of a large liquid deuterium moderator to deliver a high flux of cold neutrons and to serve secondary VCN and UCN sources, for which different options are under study. The features of these new sources will boost several areas of condensed matter research and will provide unique opportunities in fundamental physics. Part of the HighNESS project is also dedicated to the development of future instruments that will make use of the new source and will complement the initial suite of instruments in construction at ESS. The HighNESS project started in October 2020. In this paper, the ongoing developments and the results obtained in the first year are described.
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| 8. |
- Santoro, V., et al.
(författare)
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The HighNESS Project at the European Spallation Source : Current Status and Future Perspectives
- 2024
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Ingår i: Nuclear science and engineering. - 0029-5639 .- 1943-748X. ; 198:1, s. 31-63
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Tidskriftsartikel (refereegranskat)abstract
- The European Spallation Source (ESS), presently under construction in Lund, Sweden, is a multidisciplinary international laboratory that, once completed at full specifications, will operate the world's most powerful pulsed neutron source. Supported by a 3 M Euro Research and Innovation Action within the European Union Horizon 2020 program, a design study (HighNESS) is now underway to develop a second neutron source located below the spallation target. Compared to the first source, which is located above the spallation target and designed for high cold and thermal brightness, the new source is being optimized to deliver higher intensity and a shift to longer wavelengths in the spectral regions of cold neutrons (CNs) (2 to 20 & Aring;), very cold neutrons (VCNs) (10 to 120 & Aring;), and ultracold neutrons (UCNs) (> 500 & Aring;). The second source consists of a large liquid deuterium moderator to deliver CNs and serve secondary VCN and UCN sources, for which different options are under study. These new sources will boost several areas of condensed matter research and will provide unique opportunities in fundamental physics. The HighNESS project is now entering its last year, and we are working toward the Conceptual Design Report of the ESS upgrade. In this paper, results obtained in the first 2 years, ongoing developments, and future perspectives are described.
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| 9. |
- Daly, Sarah B, et al.
(författare)
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Mutations in HPSE2 cause urofacial syndrome.
- 2010
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Ingår i: American journal of human genetics. - 1537-6605. ; 86:6, s. 963-9
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Tidskriftsartikel (refereegranskat)abstract
- Urinary voiding dysfunction in childhood, manifesting as incontinence, dysuria, and urinary frequency, is a common condition. Urofacial syndrome (UFS) is a rare autosomal recessive disease characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. UFS individuals often have reflux of infected urine from the bladder to the upper renal tract, with a risk of kidney damage and renal failure. Whole-genome SNP mapping in one affected individual defined an autozygous region of 16 Mb on chromosome 10q23-q24, within which a 10 kb deletion encompassing exons 8 and 9 of HPSE2 was identified. Homozygous exonic deletions, nonsense mutations, and frameshift mutations in five further unrelated families confirmed HPSE2 as the causative gene for UFS. Mutations were not identified in four additional UFS patients, indicating genetic heterogeneity. We show that HPSE2 is expressed in the fetal and adult central nervous system, where it might be implicated in controlling facial expression and urinary voiding, and also in bladder smooth muscle, consistent with a role in renal tract morphology and function. Our findings have broader implications for understanding the genetic basis of lower renal tract malformations and voiding dysfunction.
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| 10. |
- Dian, E., et al.
(författare)
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Neutron activation and prompt gamma intensity in Ar/CO2-filled neutron detectors at the European Spallation Source
- 2017
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Ingår i: Applied Radiation and Isotopes. - : Elsevier BV. - 0969-8043 .- 1872-9800. ; 128, s. 275-286
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Tidskriftsartikel (refereegranskat)abstract
- Monte Carlo simulations using MCNP6.1 were performed to study the effect of neutron activation in Ar/CO2 neutron detector counting gas. A general MCNP model was built and validated with simple analytical calculations. Simulations and calculations agree that only the Ar-40 activation can have a considerable effect. It was shown that neither the prompt gamma intensity from the Ar-40 neutron capture nor the produced Ar-41 activity have an impact in terms of gamma dose rate around the detector and background level.
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| 11. |
- Dian, E., et al.
(författare)
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Scattered neutron background in thermal neutron detectors
- 2018
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 902, s. 173-183
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Tidskriftsartikel (refereegranskat)abstract
- Inelastic neutron scattering instruments require very low background; therefore the proper shielding for suppressing the scattered neutron background, both from elastic and inelastic scattering is essential. The detailed understanding of the background scattering sources is required for effective suppression. The Multi-Grid thermal neutron detector is an Ar/CO2 gas filled detector with a (B4C)-B-10 neutron converter coated on aluminium substrates. It is a large-area detector design that will equip inelastic neutron spectrometers at the European Spallation Source (ESS). To this end a parameterised Geant4 model is built for the Multi-Grid detector. This is the first time thermal neutron scattering background sources have been modelled in a detailed simulation of detector response. The model is validated via comparison with measured data of prototypes installed on the IN6 instrument at ILL and on the CNCS instrument at SNS. The effect of scattering originating in detector components is smaller than effects originating elsewhere.
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| 12. |
- Dian, E., et al.
(författare)
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Suppression of intrinsic neutron background in the Multi-Grid detector
- 2019
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- One of the key requirements for neutron scattering instruments is the Signal-toBackground ratio (SBR). This is as well a design driving requirement for many instruments at the European Spallation Source (ESS), which aspires to be the brightest neutron source of the world. The SBR can be effectively improved with background reduction. The Multi-Grid, a large-area thermal neutron detector with a solid boron carbide converter, is a novel solution for chopper spectrometers. This detector will be installed for the three prospective chopper spectrometers at the ESS. As the Multi-Grid detector is a large area detector with a complex structure, its intrinsic background and its suppression via advanced shielding design should be investigated in its complexity, as it cannot be naively calculated. The intrinsic scattered neutron background and its effect on the SBR is determined via a detailed Monte Carlo simulation for the Multi-Grid detector module, designed for the CSPEC instrument at the ESS. The impact of the detector vessel and the neutron entrance window on scattering is determined, revealing the importance of an optimised internal detector shielding. The background-reducing capacity of common shielding geometries, like side-shielding and end-shielding is determined by using perfect absorber as shielding material, and common shielding materials, like B4C and Cd are also tested. On the basis of the comparison of the effectiveness of the different shielding topologies and materials, recommendations are given for a combined shielding of the Multi-Grid detector module, optimised for increased SBR.
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| 13. |
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| 14. |
- Johnston, Jennifer J., et al.
(författare)
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Molecular Analysis Expands the Spectrum of Phenotypes Associated with GLI3 Mutations
- 2010
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794. ; 31:10, s. 1142-1154
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Tidskriftsartikel (refereegranskat)abstract
- A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining 93 probands here. This includes 19 probands (12 mutations) who fulfilled clinical criteria for GCPS or PHS, 48 probands (16 mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), 21 probands (6 mutations) with features of PHS or GCPS and oral-facial- digital syndrome, and 5 probands (1 mutation) with nonsyndromic polydactyly. These data support previously identified genotype-phenotype correlations and demonstrate a more variable degree of severity than previously recognized. The finding of GLI3 mutations in patients with features of oral-facial-digital syndrome supports the observation that GLI3 interacts with cilia. We conclude that the phenotypic spectrum of GLI3 mutations is broader than that encompassed by the clinical diagnostic criteria, but the genotype-phenotype correlation persists. Individuals with features of either GCPS or PHS should be screened for mutations in GLI3 even if they do not fulfill clinical criteria. Hum Mutat 31:1142-1154, 2010. (C) 2010 Wiley-Liss, Inc.
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| 15. |
- Odell, Luke R, et al.
(författare)
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The Pthaladyns : GTP Competitive Inhibitors of Dynamin I and II GTPase Derived from Virtual Screening
- 2010
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 53:14, s. 5267-5280
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Tidskriftsartikel (refereegranskat)abstract
- We report the development of a homology model for the GTP binding domain of human dynamin I based on the corresponding crystal structure of Dictyostelium discoidum dynamin A. Virtual screening identified 2-[(2-biphenyl-2-yl-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carbonyl)amino]-4-chlorobenzoic acid (1) as a 170 μM potent inhibitor. Homology modeling- and focused library-led synthesis resulted in development of a series of active compounds (the “pthaladyns”) with 4-chloro-2-(2-(4-(hydroxymethyl)phenyl)-1,3-dioxoisoindoline-5-carboxamido)benzoic acid (29), a 4.58 ± 0.06 μM dynamin I GTPase inhibitor. Pthaladyn-29 displays borderline selectivity for dynamin I relative to dynamin II (5−10 fold). Only pthaladyn-23 (dynamin I IC50 17.4 ± 5.8 μM) was an effective inhibitor of dynamin I mediated synaptic vesicle endocytosis in brain synaptosomes with an IC50 of 12.9 ± 5.9 μM. This compound was also competitive with respect to Mg2+·GTP. Thus the pthaladyns are the first GTP competitive inhibitors of dynamin I and II GTPase and may be effective new tools for the study of neuronal endocytosis.
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| 16. |
- Piscitelli, F., et al.
(författare)
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The Multi-Blade Boron-10-based neutron detector for high intensity neutron reflectometry at ESS
- 2017
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- The Multi-Blade is a Boron-10-based gaseous detector introduced to face the challenge arising in neutron reflectometry at pulsed neutron sources. Neutron reflectometers are the most challenging instruments in terms of instantaneous counting rate and spatial resolution. This detector has been designed to cope with the requirements set for the reflectometers at the upcoming European Spallation Source (ESS) in Sweden. Based on previous results obtained at the Institut Laue-Langevin (ILL) in France, an improved demonstrator has been built at ESS and tested at the Budapest Neutron Centre (BNC) in Hungary and at the Source Testing Facility (STF) at the Lund University in Sweden. A detailed description of the detector and the results of the tests are discussed in this manuscript.
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| 17. |
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| 18. |
- Sun, Yi-lin, et al.
(författare)
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Detangling the impacts of age, residential locations and household lifecycle in car usage and ownership in the Osaka metropolitan area, Japan
- 2014
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Ingår i: Zhejiang University. Journal. Science A: Applied Physics & Engineering. - 1673-565X. ; 15:7, s. 517-528
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Tidskriftsartikel (refereegranskat)abstract
- Using large cross-sectional datasets that were collected in the Osaka metropolitan area (OMA), Japan, this study systematically analyzes the structural changes in car ownership and usage in the OMA from 1970 to 2000. A simultaneous equations model system is developed for individuals that considers age, household lifecycle stage, built environment of the household location, car ownership levels, proportion of car trips on a given day, and total car travel duration. The estimation results show that private car ownership and car usage for the residents in OMA have expanded over time. Each residential area, each lifecycle stage, and each age group has their own unique characteristics of car ownership and car usage. The results further indicate that this expansion is largely due to changes in their structural relationships, while the changes in demographic factors play a relatively small and contradictory role.
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| 19. |
- Svensson, Elin M., 1985-, et al.
(författare)
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Model-based meta-analysis of rifampicin exposure and mortality in Indonesian tuberculous meningitis trials
- 2020
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 71:8, s. 1817-1823
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIntensified antimicrobial treatment with higher rifampicin doses may improve outcome of tuberculous meningitis, but the desirable exposure and necessary dose are unknown. Our objective was to characterize the relationship between rifampicin exposures and mortality in order to identify optimal dosing for tuberculous meningitis.MethodsAn individual patient meta-analysis was performed on data from 3 Indonesian randomized controlled phase 2 trials comparing oral rifampicin 450 mg (~10 mg/kg) to intensified regimens including 750–1350 mg orally, or a 600-mg intravenous infusion. Pharmacokinetic data from plasma and cerebrospinal fluid (CSF) were analyzed with nonlinear mixed-effects modeling. Six-month survival was described with parametric time-to-event models.ResultsPharmacokinetic analyses included 133 individuals (1150 concentration measurements, 170 from CSF). The final model featured 2 disposition compartments, saturable clearance, and autoinduction. Rifampicin CSF concentrations were described by a partition coefficient (5.5%; 95% confidence interval [CI], 4.5%–6.4%) and half-life for distribution plasma to CSF (2.1 hours; 95% CI, 1.3–2.9 hours). Higher CSF protein concentration increased the partition coefficient. Survival of 148 individuals (58 died, 15 dropouts) was well described by an exponentially declining hazard, with lower age, higher baseline Glasgow Coma Scale score, and higher individual rifampicin plasma exposure reducing the hazard. Simulations predicted an increase in 6-month survival from approximately 50% to approximately 70% upon increasing the oral rifampicin dose from 10 to 30 mg/kg, and predicted that even higher doses would further improve survival.ConclusionsHigher rifampicin exposure substantially decreased the risk of death, and the maximal effect was not reached within the studied range. We suggest a rifampicin dose of at least 30 mg/kg to be investigated in phase 3 clinical trials.
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