| 1. |
- Lind, Lars, et al.
(författare)
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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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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 8. |
- Sugai, H., et al.
(författare)
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Updated Design of the CMB Polarization Experiment Satellite LiteBIRD
- 2020
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Ingår i: Journal of Low Temperature Physics. - : Springer Science and Business Media LLC. - 0022-2291 .- 1573-7357. ; 199:3-4, s. 1107-1117
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Tidskriftsartikel (refereegranskat)abstract
- Recent developments of transition-edge sensors (TESs), based on extensive experience in ground-based experiments, have been making the sensor techniques mature enough for their application on future satellite cosmic microwave background (CMB) polarization experiments. LiteBIRD is in the most advanced phase among such future satellites, targeting its launch in Japanese Fiscal Year 2027 (2027FY) with JAXA's H3 rocket. It will accommodate more than 4000 TESs in focal planes of reflective low-frequency and refractive medium-and-high-frequency telescopes in order to detect a signature imprinted on the CMB by the primordial gravitational waves predicted in cosmic inflation. The total wide frequency coverage between 34 and 448 GHz enables us to extract such weak spiral polarization patterns through the precise subtraction of our Galaxy's foreground emission by using spectral differences among CMB and foreground signals. Telescopes are cooled down to 5 K for suppressing thermal noise and contain polarization modulators with transmissive half-wave plates at individual apertures for separating sky polarization signals from artificial polarization and for mitigating from instrumental 1/f noise. Passive cooling by using V-grooves supports active cooling with mechanical coolers as well as adiabatic demagnetization refrigerators. Sky observations from the second Sun-Earth Lagrangian point, L2, are planned for 3 years. An international collaboration between Japan, the USA, Canada, and Europe is sharing various roles. In May 2019, the Institute of Space and Astronautical Science, JAXA, selected LiteBIRD as the strategic large mission No. 2.
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| 10. |
- Bellaver, B., et al.
(författare)
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Astrocyte reactivity influences amyloid-beta effects on tau pathology in preclinical Alzheimer's disease
- 2023
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Ingår i: Nature Medicine. - 1078-8956. ; 29:7
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Tidskriftsartikel (refereegranskat)abstract
- Cross-sectional and longitudinal analyses of tau pathology in preclinical Alzheimer's disease reveal that tau tangles accumulate as a function of amyloid-beta burden only in individuals positive for an astrocyte reactivity biomarker. An unresolved question for the understanding of Alzheimer's disease (AD) pathophysiology is why a significant percentage of amyloid-beta (A beta)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash A beta effects in pathological tau phosphorylation. Here, in a biomarker study across three cohorts (n = 1,016), we tested whether astrocyte reactivity modulates the association of A beta with tau phosphorylation in CU individuals. We found that A beta was associated with increased plasma phosphorylated tau only in individuals positive for astrocyte reactivity (Ast(+)). Cross-sectional and longitudinal tau-positron emission tomography analyses revealed an AD-like pattern of tau tangle accumulation as a function of A beta only in CU Ast(+) individuals. Our findings suggest astrocyte reactivity as an important upstream event linking A beta with initial tau pathology, which may have implications for the biological definition of preclinical AD and for selecting CU individuals for clinical trials.
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| 11. |
- Aharonian, Felix, et al.
(författare)
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Measurements of resonant scattering in the Perseus Cluster core with Hitomi SXS
- 2018
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
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Tidskriftsartikel (refereegranskat)abstract
- Thanks to its high spectral resolution (similar to 5 eV at 6 keV), the Soft X-ray Spectrometer (SXS) on board Hitomi enables us to measure the detailed structure of spatially resolved emission lines from highly ionized ions in galaxy clusters for the first time. In this series of papers, using the SXS we have measured the velocities of gas motions, metallicities and the multi-temperature structure of the gas in the core of the Perseus Cluster. Here, we show that when inferring physical properties from line emissivities in systems like Perseus, the resonant scattering effect should be taken into account. In the Hitomi waveband, resonant scattering mostly affects the Fe XXV He alpha line (w)-the strongest line in the spectrum. The flux measured by Hitomi in this line is suppressed by a factor of similar to 1.3 in the inner similar to 30 kpc, compared to predictions for an optically thin plasma; the suppression decreases with the distance from the center. The w line also appears slightly broader than other lines from the same ion. The observed distortions of the w line flux, shape, and distance dependence are all consistent with the expected effect of the resonant scattering in the Perseus core. By measuring the ratio of fluxes in optically thick (w) and thin (Fe XXV forbidden, He beta, Ly alpha) lines, and comparing these ratios with predictions from Monte Carlo radiative transfer simulations, the velocities of gas motions have been obtained. The results are consistent with the direct measurements of gas velocities from line broadening described elsewhere in this series, although the systematic and statistical uncertainties remain significant. Further improvements in the predictions of line emissivities in plasma models, and deeper observations with future X-ray missions offering similar or better capabilities to the Hitomi SXS, will enable resonant scattering measurements to provide powerful constraints on the amplitude and anisotropy of cluster gas motions.
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| 12. |
- Aharonian, Felix, et al.
(författare)
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Temperature structure in the Perseus cluster core observed with Hitomi
- 2018
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
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Tidskriftsartikel (refereegranskat)abstract
- The present paper explains the temperature structure of X-ray emitting plasma in the core of the Perseus cluster based on 1.8-20.0 keV data obtained with the Soft X-ray Spectrometer (SXS) on board the Hitomi Observatory. A series of four observations was carried out, with a total effective exposure time of 338 ks that covered a central region of similar to 7' in diameter. SXS was operated with an energy resolution of similar to 5 eV (full width at half maximum) at 5.9 keV. Not only fine structures of K-shell lines in He-like ions, but also transitions from higher principal quantum numbers were clearly resolved from Si through Fe. That enabled us to perform temperature diagnostics using the line ratios of Si, S, Ar, Ca, and Fe, and to provide the first direct measurement of the excitation temperature and ionization temperature in the Perseus cluster. The observed spectrum is roughly reproduced by a single-temperature thermal plasma model in collisional ionization equilibrium, but detailed line-ratio diagnostics reveal slight deviations from this approximation. In particular, the data exhibit an apparent trend of increasing ionization temperature with the atomic mass, as well as small differences between the ionization and excitation temperatures for Fe, the only element for which both temperatures could be measured. The best-fit two-temperature models suggest a combination of 3 and 5 keV gas, which is consistent with the idea that the observed small deviations from a single-temperature approximation are due to the effects of projecting the known radial temperature gradient in the cluster core along the line of sight. A comparison with the Chandra/ACIS and the XMM-Newton/RGS results, on the other hand, suggests that additional lower-temperature components are present in the intracluster medium (ICM), but not detectable with Hitomi/SXS giving its 1.8-20 keV energy band.
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| 14. |
- Knuuttila, M., et al.
(författare)
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Intratumoral androgen levels are linked to TMPRSS2-ERG fusion in prostate cancer
- 2018
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Ingår i: Endocrine-Related Cancer. - : Bioscientifica. - 1351-0088 .- 1479-6821. ; 25:9, s. 807-819
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Tidskriftsartikel (refereegranskat)abstract
- Intratumoral androgen biosynthesis is one of the mechanisms involved in the progression of prostate cancer, and an important target for novel prostate cancer therapies. Using gas chromatography-tandem mass spectrometry and genome-wide RNA sequencing, we have analyzed androgen concentrations and androgen-regulated gene expression in cancerous and morphologically benign prostate tissue specimens and serum samples obtained from 48 primary prostate cancer patients. Intratumoral dihydrotestosterone (DHT) concentrations were significantly higher in the cancerous tissues compared to benign prostate (P < 0.001). The tissue/serum ratios of androgens were highly variable between the patients, indicating individual patterns of androgen metabolism and/or uptake of androgens within the prostate tissue. An unsupervised hierarchical clustering analysis of intratissue androgen concentrations indicated that transmembrane protease, serine 2/ETS-related gene (TMPRSS2-ERG)-positive patients have different androgen profiles compared to TMPRSS2-ERG- negative patients. TMPRSS2-ERG gene fusion status was also associated with an enhanced androgen-regulated gene expression, along with altered intratumoral androgen metabolism, demonstrated by reduced testosterone concentrations and increased DHT/testosterone ratios in TMPRSS2-ERG-positive tumors. TMPRSS2-ERG-positive and - negative prostate cancer specimens have distinct intratumoral androgen profiles, possibly due to activation of testosterone-independent DHT biosynthesis via the alternative pathway in TMPRSS2-ERG-positive tumors. Thus, patients with TMPRSS2-ERG-positive prostate cancer may benefit from novel inhibitors targeting the alternative DHT biosynthesis.
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| 16. |
- Stack, K. M., et al.
(författare)
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Sedimentology and Stratigraphy of the Shenandoah Formation, Western Fan, Jezero Crater, Mars
- 2024
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Ingår i: Journal of Geophysical Research: Planets. - 2169-9097. ; 129:2
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Tidskriftsartikel (refereegranskat)abstract
- Sedimentary fans are key targets of exploration on Mars because they record the history of surface aqueous activity and habitability. The sedimentary fan extending from the Neretva Vallis breach of Jezero crater's western rim is one of the Mars 2020 Perseverance rover's main exploration targets. Perseverance spent ∼250 sols exploring and collecting seven rock cores from the lower ∼25 m of sedimentary rock exposed within the fan's eastern scarp, a sequence informally named the “Shenandoah” formation. This study describes the sedimentology and stratigraphy of the Shenandoah formation at two areas, “Cape Nukshak” and “Hawksbill Gap,” including a characterization, interpretation, and depositional framework for the facies that comprise it. The five main facies of the Shenandoah formation include: laminated mudstone, laminated sandstone, low-angle cross stratified sandstone, thin-bedded granule sandstone, and thick-bedded granule-pebble sandstone and conglomerate. These facies are organized into three facies associations (FA): FA1, comprised of laminated and soft sediment-deformed sandstone interbedded with broad, unconfined coarser-grained granule and pebbly sandstone intervals; FA2, comprised predominantly of laterally extensive, soft-sediment deformed laminated, sulfate-bearing mudstone with lenses of low-angle cross-stratified and scoured sandstone; and FA3, comprised of dipping planar, thin-bedded sand-gravel couplets. The depositional model favored for the Shenandoah formation involves the transition from a sand-dominated distal alluvial fan setting (FA1) to a stable, widespread saline lake (FA2), followed by the progradation of a river delta system (FA3) into the lake basin. This sequence records the initiation of a relatively long-lived, habitable lacustrine and deltaic environment within Jezero crater.
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| 17. |
- Adam, M., et al.
(författare)
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Hydroxysteroid (17 beta) dehydrogenase 13 deficiency triggers hepatic steatosis and inflammation in mice
- 2018
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Ingår i: Faseb Journal. - 0892-6638. ; 32:6, s. 3434-3447
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxysteroid (17(3) dehydrogenases (HSD17Bs) form an enzyme family characterized by their ability to catalyze reactions in steroid and lipid metabolism. In the present study, we characterized the phenotype of HSD17B13-knockout (HSD17B13KO) mice deficient in Hsd1 7b13. In these studies, hepatic steatosis was detected in HSD17B13KO male mice, indicated by histologic analysis and by the increased triglyceride concentration in the liver, whereas reproductive performance and serum steroid concentrations were normal in HSD17B13KO mice. In line with these changes, the expression of key proteins in fatty acid synthesis, such as FAS, acetyl-CoA carboxylase 1, and SCD1, was increased in the HSD17B13KO liver. Furthermore, the knockout liver showed an increase in 2 acylcamitines, suggesting impaired mitochondrial beta-oxidation in the presence of unaltered malonyl CoA and AMPK expression. The glucose tolerance did not differ between wild-type and HSD17B13KO mice in the presence of lower levels of glucose 6-phosphatase in HSD17B13KO liver compared with wild-type liver. Furthermore, microgranulomas and increased portal inflammation together with up-regulation of immune response genes were observed in HSD17B13KO mice. Our data indicate that disruption of Hsdl7b13 impairs hepatic-lipid metabolism in mice, resulting in liver steatosis and inflammation, but the enzyme does not play a major role in the regulation of reproductive functions.
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| 21. |
- Blom, S, et al.
(författare)
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Systems pathology by multiplexed immunohistochemistry and whole-slide digital image analysis
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 15580-
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Tidskriftsartikel (refereegranskat)abstract
- The paradigm of molecular histopathology is shifting from a single-marker immunohistochemistry towards multiplexed detection of markers to better understand the complex pathological processes. However, there are no systems allowing multiplexed IHC (mIHC) with high-resolution whole-slide tissue imaging and analysis, yet providing feasible throughput for routine use. We present an mIHC platform combining fluorescent and chromogenic staining with automated whole-slide imaging and integrated whole-slide image analysis, enabling simultaneous detection of six protein markers and nuclei, and automatic quantification and classification of hundreds of thousands of cells in situ in formalin-fixed paraffin-embedded tissues. In the first proof-of-concept, we detected immune cells at cell-level resolution (n = 128,894 cells) in human prostate cancer, and analysed T cell subpopulations in different tumour compartments (epithelium vs. stroma). In the second proof-of-concept, we demonstrated an automatic classification of epithelial cell populations (n = 83,558) and glands (benign vs. cancer) in prostate cancer with simultaneous analysis of androgen receptor (AR) and alpha-methylacyl-CoA (AMACR) expression at cell-level resolution. We conclude that the open-source combination of 8-plex mIHC detection, whole-slide image acquisition and analysis provides a robust tool allowing quantitative, spatially resolved whole-slide tissue cytometry directly in formalin-fixed human tumour tissues for improved characterization of histology and the tumour microenvironment.
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