| 1. |
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| 2. |
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| 3. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 4. |
- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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| 5. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 6. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 7. |
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| 8. |
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| 9. |
- Lind, Lars, et al.
(author)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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In: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Journal article (peer-reviewed)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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| 10. |
- Bixby, H., et al.
(author)
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Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
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Journal article (peer-reviewed)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
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| 11. |
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| 13. |
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| 14. |
- Taddei, C, et al.
(author)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Journal article (peer-reviewed)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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| 15. |
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| 18. |
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| 19. |
- Zhou, Bin, et al.
(author)
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Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants
- 2016
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In: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530
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Journal article (peer-reviewed)abstract
- Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with diabetes.Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.Findings: We used data from 751 studies including 4372000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-17.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target.Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.
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| 20. |
- Adriani, O., et al.
(author)
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Secondary electron and positron fluxes in the near-Earth space observed in the ARINA and PAMELA experiments
- 2009
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In: Bulletin of the Russian Academy of Sciences: Physics. - 1062-8738. ; 73:3, s. 364-366
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Journal article (peer-reviewed)abstract
- Secondary electron and positron fluxes in the energy range from 3 MeV to 7 GeV were measured with the ARINA and PAMELA spectrometers onboard the Resurs-DK satellite launched on June 15, 2006 into an elliptical orbit with an inclination of 70.4° and an altitude of 350-600 km. It is shown that positrons dominate over electrons by a factor of up to 4-5 in the geomagnetic equator region (L < 1.2 and B > 0.25).
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| 21. |
- Adriani, O., et al.
(author)
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Positrons and electrons in primary cosmic rays as measured in the PAMELA experiment
- 2009
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In: Bulletin of the Russian Academy of Sciences: Physics. - 1062-8738. ; 73:5, s. 568-570
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Journal article (peer-reviewed)abstract
- The PAMELA experiment is being carried out on board the Russian satellite Resurs DK1 placed in the near-earth near-polar orbit on June 15, 2006. The apparatus comprising a silicon-strip magnetic spectrometer and an electromagnetic calorimeter allows measurement of electron and positron fluxes in cosmic rays in a wide energy interval from ∼100 MeV to hundreds of GeV. The high-energy electron and positron separation technique is discussed and the data on positron-to-electron ratio in primary cosmic rays up to E ≃ 10 GeV from the 2006 - 2007 measurements are reported in this work.
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| 22. |
- Galper, A. M., et al.
(author)
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International Russian-Italian mission "Rim-Pamela
- 2009
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In: Proceedings of the 13th Lomonosov Conference on Elementary Particle Physics. - : WORLD SCIENTIFIC. - 9812837582 - 9789812837585 ; , s. 199-206
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Conference paper (peer-reviewed)abstract
- The successful launch of spacecraft "RESURS DK" 1 with precision magnetic spectrometer "PAMELA" onboard was executed at Baikonur cosmodrome 15 June 2006. The primary phase of realization of International Russian-Italian Project "RIM-PAMELA" with German and Swedish scientists' participation has begun since the launch of instrument "PAMELA" that has mainly been directed to investigate the fluxes of galactic cosmic rays. This report contains the main scientific Project's tasks and the conditions of science program's implementation after one year since exploration has commenced.
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| 23. |
- Adriani, O., et al.
(author)
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The PAMELA space mission
- 2008
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In: Astroparticle, Part. Space Phys., Detect. Med. Phys. Appl. - Proc. Conf.. - : WORLD SCIENTIFIC. - 9812819088 - 9789812819086 ; , s. 858-864
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Conference paper (peer-reviewed)abstract
- The PAMELA (a Payload for Antimatter-Matter Exploration and Light-nuclei Astrophysics) experiment, is a satellite-borne particle spectrometer. It was launched on 15th June 2006 from the Baikonur cosmodrome in Kazakhstan, is installed into the Russian Resurs-DK1 satellite. PAMELA is composed of a time-of-flight system, a magnetic spectrometer, a silicon-tungsten electromagnetic calorimeter, an anticoincidence system, a shower tail catcher scintillator and a neutron detector. Among the PAMELA major objectives are the study of charged particles in the cosmic radiation, the investigation of the nature of dark matter, by mean of the measure of the cosmic-ray antiproton and positron spectra over the largest energy range ever achieved. PAMELA has been in a nearly continuous data taking mode since llth July 2006. The status of the apparatus and performances will be presented.
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| 24. |
- Boezio, M., et al.
(author)
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The first year in orbit of the pamela experiment
- 2007
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In: Proceedings of the 30th International Cosmic Ray Conference, ICRC 2007. - : Universidad Nacional Autonoma de Mexico. ; , s. 99-102
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Conference paper (peer-reviewed)abstract
- On the 15th of June 2006, the PAMELA experiment mounted on the Resurs DK1 satellite, was launched from the Baikonur cosmodrome and it has been collecting data since July 2006. PAMELA is a satellite-borne apparatus designed to study charged particles in the cosmic radiation, to investigate the nature of dark matter, measuring the cosmic-ray antiproton and positron spectra over the largest energy range ever achieved, and to search for antinuclei with unprecedented sensitivity. The PAMELA apparatus comprises a time-of-flight system, a magnetic spectrometer, a silicon-tungsten electromagnetic calorimeter, an anticoincidence system, a shower tail catcher scintillator and a neutron detector. We will present the status of the apparatus after one year in orbit. Furthermore, we will discuss the PAMELA in-flight performances.
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| 25. |
- Boezio, M., et al.
(author)
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The PAMELA space experiment : First year of operation
- 2008
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In: Journal of Physics, Conference Series. - : Institute of Physics Publishing (IOPP). - 1742-6588 .- 1742-6596. ; 110:6
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Journal article (peer-reviewed)abstract
- On the 15th of June 2006 the PAMELA experiment, mounted on the Resurs DK1 satellite, was launched from the Baikonur cosmodrome and it has been collecting data since July 2006. PAMELA is a satellite-borne apparatus designed to study charged particles in the cosmic radiation, to investigate the nature of dark matter, measuring the cosmic-ray antiproton and positron spectra over the largest energy range ever achieved, and to search for antinuclei with unprecedented sensitivity. The apparatus comprises a time-of-flight system, a silicon-microstrip magnetic spectrometer, a silicon-tungsten electromagnetic calorimeter, an anticoincidence system, a shower tail catcher scintillator and a neutron detector. The combination of these devices allows charged particle identification over a wide energy range. © 2008 IOP Publishing Ltd.
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| 26. |
- Casolino, M., et al.
(author)
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Magnetospheric and solar physics observations with the PAMELA experiment
- 2008
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 588:1-2, s. 243-246
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Journal article (peer-reviewed)abstract
- PAMELA is a satellite-borne experiment designed to make long duration measurements of the cosmic radiation in Low Earth Orbit. It is devoted to the detection of the cosmic-ray spectra in the 100 MeV-300 GeV range with primary scientific goal the measurement of antiproton and positron spectra over the largest energy range ever achieved. Other tasks include the search for antinuclei with unprecedented sensitivity and the measurement of the light nuclear component of cosmic rays. In addition, PAMELA can investigate phenomena connected with solar and Earth physics. The apparatus consists of: a Time of Flight system, a magnetic spectrometer, an electromagnetic imaging calorimeter, a shower tail catcher scintillator, a neutron detector and an anticoincidence system. In this work we present some measurements of galactic, secondary and trapped particles performed in the first months of operation.
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| 27. |
- Papini, P., et al.
(author)
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In-flight performances of the PAMELA satellite experiment
- 2008
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 588:1-2, s. 259-266
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Journal article (peer-reviewed)abstract
- PAMELA is a satcllite-borne experiment designed to study with great accuracy charged particles in the cosmic radiation with a particular focus on antiparticles. The experiment, housed on board the Russian Resurs-DK1 satellite, was launched on June 15, 2006 in a 350 x 600 km orbit with an inclination of 70 degrees. The apparatus comprises a time-of-flight system, a silicon-microstrip magnetic spectrometer, a silicon-tungsten electromagnetic calorimeter, an anticoincidence system, a shower tail catcher scintillator and a neutron detector. The combination of these devices allows charged particle identification over a wide energy range. In this work, the detector design is reviewed and the in-orbit performances in the first months after the launch are presented.
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| 28. |
- Pearce, Mark, et al.
(author)
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PAMELA : a payload for antimatter matter exploration and light-nuclei astrophysics - status and first results
- 2007
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In: 2007 IEEE NUCLEAR SCIENCE SYMPOSIUM CONFERENCE RECORD, VOLS 1-11. - 9781424409228 ; , s. 42-47
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Conference paper (peer-reviewed)abstract
- PAMELA is a satellite-borne experiment designed for precision studies of the charged cosmic radiation. The primary scientific goal is the study of the antimatter component of the cosmic radiation (antiprotons, 80 MeV - 190 GeV; and positrons, 50 MeV - 270 GeV) in order to search for evidence of dark matter particle annihilations. PAMELA will also search for primordial antinuclei (in particular, anti-helium), and test cosmic-ray propagation models through precise measurements of the antiparticle energy spectrum and studies of light nuclei and their isotopes. Concomitant goals include a study of solar physics and solar modulation during the 24th solar minimum by investigating low energy particles in the cosmic radiation; and a reconstruction of the cosmic ray electron energy spectrum up to several TeV thereby allowing a possible contribution from local sources to be studied. PAMELA is housed on-board the Russian Resurs-DK1 satellite, which was launched on June 15th 2006 in an elliptical (350-600 km altitude) orbit with an inclination of 70 degrees. PAMELA consists of a permanent magnet spectrometer, to provide rigidity and charge sign information; a Time-of-Flight and trigger system, for velocity and charge determination; a silicon-tungsten calorimeter, for lepton/hadron discrimination; and a neutron detector. An anticoincidence system is used offline to reject false triggers. In this article the PAMELA experiment and its status are reviewed. A preliminary discussion of data recorded in-orbit is also presented.
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| 29. |
- Casolino, M., et al.
(author)
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Launch of the space experiment PAMELA
- 2008
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In: Advances in Space Research. - : Elsevier. - 0273-1177 .- 1879-1948. ; 42:3, s. 455-466
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Journal article (peer-reviewed)abstract
- PAMELA is a satellite borne experiment designed to study with great accuracy cosmic rays of galactic, solar, and trapped nature in a wide energy range (protons 80 MeV-700 GeV, electrons 50 MeV-400 GeV). Main objective is the study of the antimatter component: antiprotons (80 MeV-190 GeV), positrons (50 MeV-270 GeV) and search for antimatter with a precision of the order of 10-8. The experiment, housed on board the Russian Resurs-DK I satellite, was launched on June 15th, 2006 in a 350 x 600 km orbit with all inclination of 70'. The detector is composed of a series of scintillator counters arranged at the extremities of a permanent magnet spectrometer to provide charge, time-of-flight, and rigidity information. Lepton/hadron identification is performed by a silicon-tungsten calorimeter and a neutron detector placed at the bottom of the device. An anticounter system is used offline to reject false triggers coming from the satellite. In self-trigger mode the calorimeter, the neutron detector, and a shower tail catcher are capable of an independent measure of the lepton component up to 2 TeV. In this work we describe the experiment, its scientific objectives, and the performance in the first months after launch.
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| 30. |
- Casolino, M., et al.
(author)
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Two years of flight of the Pamela experiment : Results and perspectives
- 2009
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In: Journal of the Physical Society of Japan. - 0031-9015 .- 1347-4073. ; 78:Suppl. A, s. 35-40
-
Journal article (peer-reviewed)abstract
- PAMELA is a satellite borne experiment designed to study with great accuracy cosmic rays of galactic, solar, and trapped nature in a wide energy range (protons: 80 MeV-700 GeV, electrons 50 MeV-400 GeV). Main objective is the study of the antimatter component: antiprotons (80 MeV-190 GeV), positrons (50 MeV-270 GeV) and search for antinuclei with a precision of the order of 10~8). The experiment, housed on board the Russian Resurs-DKl satellite, was launched on June, 15th 2006 in a 350 x 600 km orbit with an inclination of 70 degrees. In this work we describe the scientific objectives and the performance of PAMELA in its first two years of operation. Data on protons of trapped, secondary and galactic nature - as well as measurements of the December 13th 2006 Solar Particle Event - are also provided.
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| 31. |
- Bonvicini, V., et al.
(author)
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Performance of the PAMELA Si-W imaging calorimeter in space
- 2009
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In: Journal of Physics, Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 160, s. 012039-
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Journal article (peer-reviewed)abstract
- The Payload for Antimatter-Matter Exploration and Light Nuclei Astrophysics (PAMELA), primarily designed to directly measure antiparticles (antiprotons and positrons) in the cosmic radiation, was launched successfully on June 15th, 2006, and, since then, it is in continuous data taking. The calorimeter of the PAMELA apparatus has been designed to identify antiprotons from an electron background and positrons from a background of protons with high efficiency and rejection power. It is a sampling silicon-tungsten imaging calorimeter, which comprises 44 single-sided silicon sensor planes (380 μm thick) interleaved with 22 plates of tungsten absorber (0.74 X0 each). It is the first silicon-tungsten calorimeter to be launched in space. In this work we present the in-orbit performance of the calorimeter, including the measured identification capabilities. The calorimeter provides a proton rejection factor of ∼105 while keeping a high efficiency in selecting electrons and positrons, thus fulfilling the identification power needed to reach the primary scientific objectives of PAMELA. We show also that, after almost two years of operation in space, the calorimeter is still performing nominally.
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| 32. |
- Barocchi, M A, et al.
(author)
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A pneumococcal pilus influences virulence and host inflammatory responses
- 2006
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In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 103:8, s. 2857-2862
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Journal article (peer-reviewed)abstract
- Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality world-wide. The initial event in invasive pneumococcal disease is the attachment of encapsulated pneumococci to epithelial cells in the upper respiratory tract. This work provides evidence that initial bacterial adhesion and subsequent ability to cause invasive disease is enhanced by pili, long organelles able to extend beyond the polysaccharide capsule, previously unknown to exist in pneumococci. These adhesive pili-like appendages are encoded by the pneumococcal rlrA islet, present in some, but not all, clinical isolates. Introduction of the rlrA islet into an encapsulated rlrA-negative isolate allowed pilus expression, enhanced adherence to lung epithelial cells, and provided a competitive advantage upon mixed intranasal challenge of mice. Furthermore, a pilus-expressing rlrA islet-positive clinical isolate was more virulent than a nonpiliated deletion mutant, and it out-competed the mutant in murine models of colonization, pneumonia, and bacteremia. Additionally, piliated pneumococci evoked a higher TNF response during systemic infection, compared with nonpiliated derivatives, suggesting that pneumococcal pili not only contribute to adherence and virulence but also stimulate the host inflammatory response.
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| 33. |
- Casolino, M., et al.
(author)
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Cosmic ray measurements with Pamela experiment
- 2009
-
Conference paper (peer-reviewed)abstract
- PAMELA is a satellite borne experiment designed to study with great accuracy cosmic rays of galactic, solar, and trapped nature hi a wide energy range (protons: 80 MeV-700 GeV, electrons 50 MeV-400 GeV). Main objective is the study of the antimatter component: antiprotons (80 MeV-190 GeV), positrons (50 MeV-270 GeV) and search for antinuclei with a precision of the order of 10(-8)). The experiment, housed on board the Russian Resurs-DK1 satellite, was launched on June, 15(th) 2006 in a 350 X 600 km orbit with an inclination of 70 degrees. In this work we describe the scientific objectives awl the performance of PAMELA in its first two years of operation. Data oil protons of trapped, secondary and galactic nature - as well as measurements of the December 13(th) 2006 Solar Particle Event - are also provided.
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| 34. |
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| 35. |
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| 36. |
- Alexander, Y, et al.
(author)
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Endothelial function in cardiovascular medicine: a consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology, Aorta and Peripheral Vascular Diseases, Coronary Pathophysiology and Microcirculation, and Thrombosis
- 2021
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In: Cardiovascular research. - : Oxford University Press (OUP). - 1755-3245 .- 0008-6363. ; 117:1, s. 29-42
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Journal article (peer-reviewed)abstract
- Endothelial cells (ECs) are sentinels of cardiovascular health. Their function is reduced by the presence of cardiovascular risk factors, and is regained once pathological stimuli are removed. In this European Society for Cardiology Position Paper, we describe endothelial dysfunction as a spectrum of phenotypic states and advocate further studies to determine the role of EC subtypes in cardiovascular disease. We conclude that there is no single ideal method for measurement of endothelial function. Techniques to measure coronary epicardial and micro-vascular function are well established but they are invasive, time-consuming, and expensive. Flow-mediated dilatation (FMD) of the brachial arteries provides a non-invasive alternative but is technically challenging and requires extensive training and standardization. We, therefore, propose that a consensus methodology for FMD is universally adopted to minimize technical variation between studies, and that reference FMD values are established for different populations of healthy individuals and patient groups. Newer techniques to measure endothelial function that are relatively easy to perform, such as finger plethysmography and the retinal flicker test, have the potential for increased clinical use provided a consensus is achieved on the measurement protocol used. We recommend further clinical studies to establish reference values for these techniques and to assess their ability to improve cardiovascular risk stratification. We advocate future studies to determine whether integration of endothelial function measurements with patient-specific epigenetic data and other biomarkers can enhance the stratification of patients for differential diagnosis, disease progression, and responses to therapy.
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| 37. |
- Chatterjee, P., et al.
(author)
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Plasma metabolites associated with biomarker evidence of neurodegeneration in cognitively normal older adults
- 2021
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In: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 159:2, s. 389-402
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Journal article (peer-reviewed)abstract
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently has no cure. Identifying biochemical changes associated with neurodegeneration prior to symptom onset, will provide insight into the biological mechanisms associated with neurodegenerative processes, that may also aid in identifying potential drug targets. The current study therefore investigated associations between plasma neurofilament light chain (NF-L), a marker of neurodegeneration, with plasma metabolites that are products of various cellular processes. Plasma NF-L, measured by ultrasensitive Single molecule array (Simoa) technology (Quanterix) and plasma metabolites, measured by mass-spectrometry (AbsoluteIDQ (R) p400HR kit, BIOCRATES), were assessed in the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohort comprising 100 cognitively normal older adults. Metabolites belonging to biogenic amine (creatinine, symmetric dimethylarginine, asymmetric dimethylarginine; ADMA, kynurenine, trans-4-hydroxyproline), amino acid (citrulline, proline, arginine, asparagine, phenylalanine, threonine) and acylcarnitine classes were observed to have positive correlations with plasma NF-L, suggesting a link between neurodegeneration and biological pathways associated with neurotransmitter regulation, nitric oxide homoeostasis, inflammation and mitochondrial function. Additionally, after stratifying participants based on low/high brain amyloid-beta load (A beta +/-) assessed by positron emission tomography, while creatinine, SDMA and citrulline correlated with NF-L in both A beta- and A beta+ groups, ADMA, proline, arginine, asparagine, phenylalanine and acylcarnitine species correlated with NF-L only in the A beta+ group after adjusting for confounding variables, suggesting that the association of these metabolites with neurodegeneration may be relevant to AD-related neuropathology. Metabolites identified to be associated with plasma NF-L may have the potential to serve as prognostic markers for neurodegenerative diseases, however, further studies are required to validate the current findings in an independent cohort, both cross-sectionally and longitudinally.
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| 38. |
- Chatterjee, P., et al.
(author)
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Serum Hepcidin Levels in Cognitively Normal Older Adults with High Neocortical Amyloid-beta Load
- 2020
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In: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 76:1, s. 291-301
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Journal article (peer-reviewed)abstract
- Background/Objective: Hepcidin, an iron-regulating hormone, suppresses the release of iron by binding to the iron exporter protein, ferroportin, resulting in intracellular iron accumulation. Given that iron dyshomeostasis has been observed in Alzheimer's disease (AD) together with elevated serum hepcidin levels, the current study examined whether elevated serum hepcidin levels are an early event in AD pathogenesis by measuring the hormone in cognitively normal older adults at risk of AD, based on high neocortical amyloid-beta load (NAL). Methods: Serum hepcidin levels in cognitively normal participants (n = 100) aged between 65-90 years were measured using ELISA. To evaluate NAL, all participants underwent 18F-florbetaben positron emission tomography. A standard uptake value ratio (SUVR)<1.35 was classified as low NAL (n = 65) and >= 1.35 (n = 35) was classified as high NAL. Results: Serum hepcidin was significantly higher in participants with high NAL compared to those with low NAL before and after adjusting for covariates: age, gender, and APOE epsilon 4 carriage (p < 0.05). A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished high from low NAL (area under the curve, AUC = 0.766), but was outperformed when serum hepcidin was added to the base model (AUC = 0.794) and further improved with plasma A beta(42/40) ratio (AUC = 0.829). Conclusion: The present findings indicate that serum hepcidin is increased in individuals at risk for AD and contribute to the body of evidence supporting iron dyshomeostasis as an early event of AD. Further, hepcidin may add value to a panel of markers that contribute toward identifying individuals at risk of AD; however, further validation studies are required.
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| 39. |
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| 40. |
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| 41. |
- Frye, Maike, et al.
(author)
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Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program
- 2018
-
In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
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Journal article (peer-reviewed)abstract
- Tissue and vessel wall stiffening alters endothelial cell properties and contributes to vascular dysfunction. However, whether extracellular matrix (ECM) stiffness impacts vascular development is not known. Here we show that matrix stiffness controls lymphatic vascular morphogenesis. Atomic force microscopy measurements in mouse embryos reveal that venous lymphatic endothelial cell (LEC) progenitors experience a decrease in substrate stiffness upon migration out of the cardinal vein, which induces a GATA2-dependent transcriptional program required to form the first lymphatic vessels. Transcriptome analysis shows that LECs grown on a soft matrix exhibit increased GATA2 expression and a GATA2-dependent upregulation of genes involved in cell migration and lymphangiogenesis, including VEGFR3. Analyses of mouse models demonstrate a cell-autonomous function of GATA2 in regulating LEC responsiveness to VEGF-C and in controlling LEC migration and sprouting in vivo. Our study thus uncovers a mechanism by which ECM stiffness dictates the migratory behavior of LECs during early lymphatic development.
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| 43. |
- Giraud, Antoine, et al.
(author)
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Costs and benefits of high mutation rates : adaptive evolution of bacteria in the mouse gut.
- 2001
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 291:5513, s. 2606-8
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Journal article (peer-reviewed)abstract
- We have shown that bacterial mutation rates change during the experimental colonization of the mouse gut. A high mutation rate was initially beneficial because it allowed faster adaptation, but this benefit disappeared once adaptation was achieved. Mutator bacteria accumulated mutations that, although neutral in the mouse gut, are often deleterious in secondary environments. Consistently, the competitiveness of mutator bacteria is reduced during transmission to and re-colonization of similar hosts. The short-term advantages and long-term disadvantages of mutator bacteria could account for their frequency in nature.
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| 44. |
- Giraud, A, et al.
(author)
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The rise and fall of mutator bacteria.
- 2001
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In: Current Opinion in Microbiology. - 1369-5274 .- 1879-0364. ; 4:5, s. 582-5
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Journal article (peer-reviewed)abstract
- Bacteria with elevated mutation rates are frequently found among natural isolates. This is probably because of their ability to generate genetic variability, the substrate for natural selection. However, such high mutation rates can lead to the loss of vital functions. The evolution of bacterial populations may happen through alternating periods of high and low mutation rates. The cost and benefits of high mutation rates in the course of bacterial adaptive evolution are reviewed.
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| 45. |
- Kakogiannos, Nikolaos, et al.
(author)
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JAM-A Acts via C/EBP-alpha to Promote Claudin-5 Expression and Enhance Endothelial Barrier Function
- 2020
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In: Circulation Research. - : Lippincott Williams & Wilkins. - 0009-7330 .- 1524-4571. ; 127:8, s. 1056-1073
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Journal article (peer-reviewed)abstract
- Rationale: Intercellular tight junctions are crucial for correct regulation of the endothelial barrier. Their composition and integrity are affected in pathological contexts, such as inflammation and tumor growth. JAM-A (junctional adhesion molecule A) is a transmembrane component of tight junctions with a role in maintenance of endothelial barrier function, although how this is accomplished remains elusive.Objective: We aimed to understand the molecular mechanisms through which JAM-A expression regulates tight junction organization to control endothelial permeability, with potential implications under pathological conditions.Methods and Results: Genetic deletion of JAM-A in mice significantly increased vascular permeability. This was associated with significantly decreased expression of claudin-5 in the vasculature of various tissues, including brain and lung. We observed that C/EBP-α (CCAAT/enhancer-binding protein-α) can act as a transcription factor to trigger the expression of claudin-5 downstream of JAM-A, to thus enhance vascular barrier function. Accordingly, gain-of-function for C/EBP-α increased claudin-5 expression and decreased endothelial permeability, as measured by the passage of fluorescein isothiocyanate (FITC)-dextran through endothelial monolayers. Conversely, C/EBP-α loss-of-function showed the opposite effects of decreased claudin-5 levels and increased endothelial permeability. Mechanistically, JAM-A promoted C/EBP-α expression through suppression of β-catenin transcriptional activity, and also through activation of EPAC (exchange protein directly activated by cAMP). C/EBP-α then directly binds the promoter of claudin-5 to thereby promote its transcription. Finally, JAM-A–C/EBP-α–mediated regulation of claudin-5 was lost in blood vessels from tissue biopsies from patients with glioblastoma and ovarian cancer.Conclusions: We describe here a novel role for the transcription factor C/EBP-α that is positively modulated by JAM-A, a component of tight junctions that acts through EPAC to up-regulate the expression of claudin-5, to thus decrease endothelial permeability. Overall, these data unravel a regulatory molecular pathway through which tight junctions limit vascular permeability. This will help in the identification of further therapeutic targets for diseases associated with endothelial barrier dysfunction.
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