| 41. |
- Payne, T., et al.
(författare)
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Prospective analysis of plasma amyloid beta and postoperative delirium in the Interventions for Postoperative Delirium: Biomarker-3 study
- 2023
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912. ; 130:5, s. 546-556
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Tidskriftsartikel (refereegranskat)abstract
- Background: The effect of postoperative delirium on the amyloid cascade of Alzheimer's dementia is poorly understood. Using early postoperative plasma biomarkers, we explored whether surgery and delirium are associated with changes in amyloid pathways.Methods: We analysed data from 100 participants in the Interventions for Postoperative Delirium: Biomarker-3 (IPOD-B3) cohort study in the USA (NCT03124303 and NCT01980511), which recruited participants aged >65 yr undergoing non-intracranial surgery. We assessed the relationship between the change in plasma amyloid beta ratio (A(3R; A(342:A(340) and delirium incidence (defined by the 3-Minute Diagnostic Confusion Assessment Method) and severity (quantified by the Delirium Rating Scale-Revised-98, the study's primary outcome). We also tested the relationship between plasma amyloid beta and intraoperative variables.Results: Across all participants, the plasma A(3R increased from the preoperative period to postoperative Day 1 (Wilcoxon P<0.001). However, this increase was not associated with delirium incidence (Wilcoxon P=0.22) or peak severity after adjusting for confounders (log[incidence rate ratio]=0.43; P=0.14). Postoperative Day 1 change in plasma A(3R was not associated with postoperative Day 1 change in plasma tau, neurofilament light, or inflammatory markers (interleukin [IL]-1(3, IL-1Ra, IL-2, IL-4, IL-6, IL-8, IL-10, and IL-12), or with operative time or low intraoperative arterial pressure.Conclusions: Perioperative changes in plasma amyloid do not appear to be associated with postoperative delirium. Our findings do not support associations of dynamic changes in amyloid with postoperative delirium.Clinical trial registration: NCT03124303 and NCT01980511.
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| 42. |
- Seyed Khoei, Nazlisadat, et al.
(författare)
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Circulating bilirubin levels and risk of colorectal cancer : serological and Mendelian randomization analyses
- 2020
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Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (Pheterogeneity ≥ 0.2).CONCLUSIONS: Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.
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| 43. |
- Taylor, J., et al.
(författare)
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Postoperative delirium and changes in the blood–brain barrier, neuroinflammation, and cerebrospinal fluid lactate: a prospective cohort study
- 2022
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912. ; 129:2, s. 219-230
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Tidskriftsartikel (refereegranskat)abstract
- Background: Case-control studies have associated delirium with blood–brain barrier (BBB) permeability. However, this approach cannot determine whether delirium is attributable to high pre-existing permeability or to perioperative changes. We tested whether perioperative changes in cerebrospinal fluid/plasma albumin ratio (CPAR) and plasma S100B were associated with delirium severity. Methods: Participants were recruited to two prospective cohort studies of non-intracranial surgery (NCT01980511, NCT03124303, and NCT02926417). Delirium severity was assessed using the Delirium Rating Scale-98. Delirium incidence was diagnosed with the 3D-Confusion Assessment Method (3D-CAM) or CAM-ICU (CAM for the ICU). CSF samples from 25 patients and plasma from 78 patients were analysed for albumin and S100B. We tested associations between change in CPAR (n=11) and S100B (n=61) and delirium, blood loss, CSF interleukin-6 (IL-6), and CSF lactate. Results: The perioperative increase in CPAR and S100B correlated with delirium severity (CPAR ρ=0.78, P=0.01; S100B ρ=0.41, P<0.001), delirium incidence (CPAR P=0.012; S100B P<0.001) and CSF IL-6 (CPAR ρ=0.66 P=0.04; S100B ρ=0.75, P=0.025). Linear mixed-effect analysis also showed that decreased levels of S100B predicted recovery from delirium symptoms (P=0.001). Linear regression demonstrated that change in plasma S100B was independently associated with surgical risk, cardiovascular surgery, blood loss, and hypotension. Blood loss also correlated with CPAR (ρ=0.64, P=0.04), S100B (ρ=0.70, P<0.001), CSF lactate (R=0.81, P=0.01), and peak delirium severity (ρ=0.36, P=0.01). Conclusion: Postoperative delirium is associated with a breakdown in the BBB. This increased permeability is dynamic and associated with a neuroinflammatory and lactate response. Strategies to mitigate blood loss may protect the BBB. © 2022 British Journal of Anaesthesia
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| 44. |
- Traven, G., et al.
(författare)
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The GALAH survey : multiple stars and our Galaxy: I. A comprehensive method for deriving properties of FGK binary stars?
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 638
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Tidskriftsartikel (refereegranskat)abstract
- Context. Binary stellar systems form a large fraction of the Galaxy's stars. They are useful as laboratories for studying the physical processes taking place within stars, and must be correctly taken into account when observations of stars are used to study the structure and evolution of the Galaxy. The advent of large-scale spectroscopic and photometric surveys allows us to obtain large samples of binaries that permit characterising their populations.Aims. We aim to obtain a large sample of double-lined spectroscopic binaries (SB2s) by analysis of spectra from the GALAH survey in combination with photometric and astrometric data. A combined analysis will provide stellar parameters of thousands of binary stars that can be combined to form statistical observables of a given population. We aim to produce a catalogue of well-characterised systems, which can in turn be compared to models of populations of binary stars, or to follow-up individual systems of interest.Methods. We obtained a list of candidate SB2 systems from a t-distributed stochastic neighbour embedding (t-SNE) classification and a cross-correlation analysis of GALAH spectra. To compute parameters of the primary and secondary star, we used a Bayesian approach that includes a parallax prior from Gaia DR2, spectra from GALAH, and apparent magnitudes from APASS, Gaia DR2, 2MASS, and WISE. We used a Markov chain Monte Carlo approach to sample the posterior distributions of the following model parameters for the two stars: T-eff[1,T-2], logg([1,2]), [Fe/H], V-r[1,V-2], v(mic[1,2]), v(broad[1,2]), R-[1,R-2], and E(B-V).Results. We present results for 12 760 binary stars detected as SB2s. We construct the statistical observables T-1/T-2, Delta V-r, and R-1/R-2, which demonstrate that our sample mostly consists of dwarfs, with a significant fraction of evolved stars and several dozen members of the giant branch. The majority of these binary stars is concentrated at the lower boundary of the Delta V-r distribution, and the R-1/R-2 ratio is mostly close to unity. The derived metallicity of our binary stars is statistically lower than that of single dwarf stars from the same magnitude-limited sample.Conclusions. Our sample of binary stars represents a large population of well-characterised double-lined spectroscopic binaries that are appropriate for statistical studies of the binary populations. The derived stellar properties and their distributions show trends that are expected for a population of close binary stars (a < 10 AU) detected through double lines in their spectra. Our detection technique allows us to probe binary systems with mass ratios 0.5 q <= 1.
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| 45. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 46. |
- Yong, D., et al.
(författare)
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High-resolution spectroscopic follow-up of the most metal-poor candidates from SkyMapper DR1.1
- 2021
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 507:3, s. 4102-4119
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Tidskriftsartikel (refereegranskat)abstract
- We present chemical abundances for 21 elements (from Li to Eu) in 150 metal-poor Galactic stars spanning −4.1 < [Fe/H] < −2.1. The targets were selected from the SkyMapper survey and include 90 objects with [Fe/H] ≤ −3 of which some 15 have [Fe/H] ≤ −3.5. When combining the sample with our previous studies, we find that the metallicity distribution function has a power-law slope of Δ(log N)/Δ[Fe/H] = 1.51 ± 0.01 dex per dex over the range −4 ≤ [Fe/H] ≤ −3. With only seven carbon-enhanced metal-poor stars in the sample, we again find that the selection of metal-poor stars based on SkyMapper filters is biased against highly carbon-rich stars for [Fe/H] > −3.5. Of the 20 objects for which we could measure nitrogen, 11 are nitrogen-enhanced metal-poor (NEMP) stars. Within our sample, the high NEMP fraction (55 per cent ± 21 per cent) is compatible with the upper range of predicted values (between 12 per cent and 35 per cent). The chemical abundance ratios [X/Fe] versus [Fe/H] exhibit similar trends to previous studies of metal-poor stars and Galactic chemical evolution models. We report the discovery of nine new r-I stars, four new r-II stars, one of which is the most metal-poor known, nine low-α stars with [α/Fe] ≤ 0.15 as well as one unusual star with [Zn/Fe] = +1.4 and [Sr/Fe] = +1.2 but with normal [Ba/Fe]. Finally, we combine our sample with literature data to provide the most extensive view of the early chemical enrichment of the Milky Way Galaxy.
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| 47. |
- Yong, D., et al.
(författare)
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r-Process elements from magnetorotational hypernovae
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 595:7866, s. 223-226
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Tidskriftsartikel (refereegranskat)abstract
- Neutron-star mergers were recently confirmed as sites of rapid-neutron-capture (r-process) nucleosynthesis(1-3). However, in Galactic chemical evolution models, neutron-star mergers alone cannot reproduce the observed element abundance patterns of extremely metal-poor stars, which indicates the existence of other sites of r-process nucleosynthesis(4-6). These sites may be investigated by studying the element abundance patterns of chemically primitive stars in the halo of the Milky Way, because these objects retain the nucleosynthetic signatures of the earliest generation of stars(7-13). Here we report the element abundance pattern of the extremely metal-poor star SMSS J200322.54-114203.3. We observe a large enhancement in r-process elements, with very low overall metallicity. The element abundance pattern is well matched by the yields of a single 25-solar-mass magnetorotational hypernova. Such a hypernova could produce not only the r-process elements, but also light elements during stellar evolution, and iron-peak elements during explosive nuclear burning. Hypernovae are often associated with long-duration gamma-ray bursts in the nearby Universe(8). This connection indicates that similar explosions of fast-spinning strongly magnetized stars occurred during the earliest epochs of star formation in our Galaxy.
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| 48. |
- Alejandre, Elizabeth M., et al.
(författare)
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Characterization Factors to Assess Land Use Impacts on Pollinator Abundance in Life Cycle Assessment
- 2023
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 57:8, s. 3445-3454
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Tidskriftsartikel (refereegranskat)abstract
- While wild pollinators play a key role in global food production, their assessment is currently missing from the most commonly used environmental impact assessment method, Life Cycle Assessment (LCA). This is mainly due to constraints in data availability and compatibility with LCA inventories. To target this gap, relative pollinator abundance estimates were obtained with the use of a Delphi assessment, during which 25 experts, covering 16 nationalities and 45 countries of expertise, provided scores for low, typical, and high expected abundance associated with 24 land use categories. Based on these estimates, this study presents a set of globally generic characterization factors (CFs) that allows translating land use into relative impacts to wild pollinator abundance. The associated uncertainty of the CFs is presented along with an illustrative case to demonstrate the applicability in LCA studies. The CFs based on estimates that reached consensus during the Delphi assessment are recommended as readily applicable and allow key differences among land use types to be distinguished. The resulting CFs are proposed as the first step for incorporating pollinator impacts in LCA studies, exemplifying the use of expert elicitation methods as a useful tool to fill data gaps that constrain the characterization of key environmental impacts.
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| 49. |
- Ballweg, Tyler, et al.
(författare)
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Association between plasma tau and postoperative delirium incidence and severity: a prospective observational study.
- 2021
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Ingår i: British journal of anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 126:2, s. 458-466
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Tidskriftsartikel (refereegranskat)abstract
- Postoperative delirium is associated with increases in the neuronal injury biomarker, neurofilament light (NfL). Here we tested whether two other biomarkers, glial fibrillary acidic protein (GFAP) and tau, are associated with postoperative delirium.A total of 114 surgical patients were recruited into two prospective biomarker cohort studies with assessment of delirium severity and incidence. Plasma samples were sent for biomarker analysis including tau, NfL, and GFAP, and a panel of 10 cytokines. We determined a priori to adjust for interleukin-8 (IL-8), a marker of inflammation, when assessing associations between biomarkers and delirium incidence and severity.GFAP concentrations showed no relationship to delirium. The change in tau from preoperative concentrations to postoperative Day 1 was greater in patients with postoperative delirium (P<0.001) and correlated with delirium severity (ρ=0.39, P<0.001). The change in tau correlated with increases in IL-8 (P<0.001) and IL-10 (P=0.0029). Linear regression showed that the relevant clinical predictors of tau changes were age (P=0.037), prior stroke/transient ischaemic attack (P=0.001), and surgical blood loss (P<0.001). After adjusting for age, sex, preoperative cognition, and change in IL-8, tau remained significantly associated with delirium severity (P=0.026). Using linear mixed effect models, only tau (not NfL or IL-8) predicted recovery from delirium (P<0.001).The change in plasma tau was associated with delirium incidence and severity, and resolved over time in parallel with delirium features. The impact of this putative perioperative neuronal injury biomarker on long-term cognition merits further investigation.NCT02926417 and NCT03124303.
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| 50. |
- Buder, Sven, et al.
(författare)
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The GALAH plus survey : Third data release
- 2021
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 506:1, s. 150-201
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Tidskriftsartikel (refereegranskat)abstract
- The ensemble of chemical element abundance measurements for stars, along with precision distances and orbit properties, provides high-dimensional data to study the evolution of the Milky Way. With this third data release of the Galactic Archaeology with HERMES (GALAH) survey, we publish 678 423 spectra for 588 571 mostly nearby stars (81.2 per cent of stars are within <2 kpc), observed with the HERMES spectrograph at the Anglo-Australian Telescope. This release (hereafter GALAH+ DR3) includes all observations from GALAH Phase 1 (bright, main, and faint survey, 70 per cent), K2-HERMES (17 per cent), TESS-HERMES (5 per cent), and a subset of ancillary observations (8 per cent) including the bulge and >75 stellar clusters. We derive stellar parameters T-eff, logg, [Fe/H], v(mic), v(broad), and v(rad) using our modified version of the spectrum synthesis code Spectroscopy Made Easy (SME) and 1D MARCS model atmospheres. We break spectroscopic degeneracies in our spectrum analysis with astrometry from Gaia DR2 and photometry from 2MASS. We report abundance ratios [X/Fe] for 30 different elements (11 of which are based on non-LTE computations) covering five nucleosynthetic pathways. We describe validations for accuracy and precision, flagging of peculiar stars/measurements and recommendations for using our results. Our catalogue comprises 65 per cent dwarfs, 34 per cent giants, and 1 per cent other/unclassified stars. Based on unflagged chemical composition and age, we find 62 per cent young low-alpha, 9 per cent young high-alpha, 27 per cent old high-alpha, and 2 per cent stars with [Fe/H] <= -1. Based on kinematics, 4 per cent are halo stars. Several Value-Added-Catalogues, including stellar ages and dynamics, updated after Gaia eDR3, accompany this release and allow chrono-chemodynamic analyses, as we showcase.
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