| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
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| 3. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 9. |
- Algaba, Juan-Carlos, et al.
(författare)
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Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
- 2021
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
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Forskningsöversikt (refereegranskat)abstract
- In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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| 10. |
- Coignard, J, et al.
(författare)
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A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1078-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
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| 17. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 18. |
- Fazey, Ioan, et al.
(författare)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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| 19. |
- Maron, David J., et al.
(författare)
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Initial Invasive or Conservative Strategy for Stable Coronary Disease
- 2020
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:15, s. 1395-1407
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Tidskriftsartikel (refereegranskat)abstract
- Background: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain.Methods: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction.Results: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32).Conclusions: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, .) Patients with stable coronary disease were randomly assigned to an initial invasive strategy with angiography and revascularization if appropriate or to medical therapy alone. At 3.2 years, there was no significant difference between the groups with respect to the estimated rate of ischemic events. The findings were sensitive to the definition of myocardial infarction.
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| 20. |
- Middha, Pooja K., et al.
(författare)
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A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry
- 2023
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Ingår i: Breast Cancer Research. - : BioMed Central (BMC). - 1465-5411 .- 1465-542X. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Genome-wide studies of gene-environment interactions (GxE) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide GxE analysis of similar to 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 x 10(-5) prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). Conclusions Overall, the contribution of GxE interactions to the heritability of breast cancer is very small. At the population level, multiplicative GxE interactions do not make an important contribution to risk prediction in breast cancer.
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| 21. |
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| 22. |
- Camacho-Neves, Yssavo, et al.
(författare)
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Over 500 Days in the Life of the Photosphere of the Type Iax Supernova SN 2014dt
- 2023
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 951:1
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Tidskriftsartikel (refereegranskat)abstract
- Type Iax supernovae (SNe Iax) are the largest known class of peculiar white dwarf SNe, distinct from normal Type Ia supernovae (SNe Ia). The unique properties of SNe Iax, especially their strong photospheric lines out to extremely late times, allow us to model their optical spectra and derive the physical parameters of the long-lasting photosphere. We present an extensive spectral timeseries, including 21 new spectra, of SN Iax 2014dt from +11 to +562 days after maximum light. We are able to reproduce the entire timeseries with a self-consistent, nearly unaltered deflagration explosion model from Fink et al. using TARDIS, an open source radiative-transfer code. We find that the photospheric velocity of SN 2014dt slows its evolution between +64 and +148 days, which closely overlaps the phase when we see SN 2014dt diverge from the normal spectral evolution of SNe Ia (+90 to +150 days). The photospheric velocity at these epochs, ∼400–1000 km s−1, may demarcate a boundary within the ejecta below which the physics of SNe Iax and normal SNe Ia differ. Our results suggest that SN 2014dt is consistent with a weak deflagration explosion model that leaves behind a bound remnant and drives an optically thick, quasi-steady-state wind creating the photospheric lines at late times. The data also suggest that this wind may weaken at epochs past +450 days, perhaps indicating a radioactive power source that has decayed away.
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| 23. |
- Festari, Cristina, et al.
(författare)
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European consensus for the diagnosis of MCI and mild dementia : Preparatory phase
- 2023
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:5, s. 1729-1741
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Etiological diagnosis of neurocognitive disorders of middle-old age relies on biomarkers, although evidence for their rational use is incomplete. A European task force is defining a diagnostic workflow where expert experience fills evidence gaps for biomarker validity and prioritization. We report methodology and preliminary results. Methods: Using a Delphi consensus method supported by a systematic literature review, 22 delegates from 11 relevant scientific societies defined workflow assumptions. Results: We extracted diagnostic accuracy figures from literature on the use of biomarkers in the diagnosis of main forms of neurocognitive disorders. Supported by this evidence, panelists defined clinical setting (specialist outpatient service), application stage (MCI-mild dementia), and detailed pre-assessment screening (clinical-neuropsychological evaluations, brain imaging, and blood tests). Discussion: The Delphi consensus on these assumptions set the stage for the development of the first pan-European workflow for biomarkers’ use in the etiological diagnosis of middle-old age neurocognitive disorders at MCI-mild dementia stages. Highlights: Rational use of biomarkers in neurocognitive disorders lacks consensus in Europe. A consensus of experts will define a workflow for the rational use of biomarkers. The diagnostic workflow will be patient-centered and based on clinical presentation. The workflow will be updated as new evidence accrues.
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| 24. |
- Frisoni, Giovanni B., et al.
(författare)
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European intersocietal recommendations for the biomarker-based diagnosis of neurocognitive disorders
- 2024
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Ingår i: The Lancet Neurology. - 1474-4422 .- 1474-4465. ; 23:3, s. 302-312
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Forskningsöversikt (refereegranskat)abstract
- The recent commercialisation of the first disease-modifying drugs for Alzheimer's disease emphasises the need for consensus recommendations on the rational use of biomarkers to diagnose people with suspected neurocognitive disorders in memory clinics. Most available recommendations and guidelines are either disease-centred or biomarker-centred. A European multidisciplinary taskforce consisting of 22 experts from 11 European scientific societies set out to define the first patient-centred diagnostic workflow that aims to prioritise testing for available biomarkers in individuals attending memory clinics. After an extensive literature review, we used a Delphi consensus procedure to identify 11 clinical syndromes, based on clinical history and examination, neuropsychology, blood tests, structural imaging, and, in some cases, EEG. We recommend first-line and, if needed, second-line testing for biomarkers according to the patient's clinical profile and the results of previous biomarker findings. This diagnostic workflow will promote consistency in the diagnosis of neurocognitive disorders across European countries.
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| 25. |
- Im, Annie, et al.
(författare)
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Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide
- 2020
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 26:8, s. 1459-1468
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Tidskriftsartikel (refereegranskat)abstract
- Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.
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| 26. |
- Laverse, Etienne, et al.
(författare)
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Plasma glial fibrillary acidic protein and neurofilament light chain, but not tau, are biomarkers of sports-related mild traumatic brain injury.
- 2020
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Ingår i: Brain communications. - : Oxford University Press (OUP). - 2632-1297. ; 2:2
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Tidskriftsartikel (refereegranskat)abstract
- Mild traumatic brain injury is a relatively common event in contact sports and there is increasing interest in the long-term neurocognitive effects. The diagnosis largely relies on symptom reporting and there is a need for objective tools to aid diagnosis and prognosis. There are recent reports that blood biomarkers could potentially help triage patients with suspected injury and normal CT findings. We have measured plasma concentrations of glial and neuronal proteins and explored their potential in the assessment of mild traumatic brain injury in contact sport. We recruited a prospective cohort of active male rugby players, who had pre-season baseline plasma sampling. From this prospective cohort, we recruited 25 players diagnosed with mild traumatic brain injury. We sampled post-match rugby players without head injuries as post-match controls. We measured plasma neurofilament light chain, tau and glial fibrillary acidic protein levels using ultrasensitive single molecule array technology. The data were analysed at the group and individual player level. Plasma glial fibrillary acidic protein concentration was significantly increased 1-h post-injury in mild traumatic brain injury cases compared to the non-injured group (P=0.017). Pairwise comparison also showed that glial fibrillary acidic protein levels were higher in players after a head injury in comparison to their pre-season levels at both 1-h and 3- to 10-day post-injury time points (P=0.039 and 0.040, respectively). There was also an increase in neurofilament light chain concentration in brain injury cases compared to the pre-season levels within the same individual at both time points (P=0.023 and 0.002, respectively). Tau was elevated in both the non-injured control group and the 1-h post-injury group compared to pre-season levels (P=0.007 and 0.015, respectively). Furthermore, receiver operating characteristic analysis showed that glial fibrillary acidic protein and neurofilament light chain can separate head injury cases from control players. The highest diagnostic power was detected when biomarkers were combined in differentiating 1-h post-match control players from 1-h post-head injury players (area under curve 0.90, 95% confidence interval 0.79-1.00, P<0.0002). The brain astrocytic marker glial fibrillary acidic protein is elevated in blood 1h after mild traumatic brain injury and in combination with neurofilament light chain displayed the potential as a reliable biomarker for brain injury evaluation. Plasma total tau is elevated following competitive rugby with and without a head injury, perhaps related to peripheral nerve trauma and therefore total tau does not appear to be suitable as a blood biomarker.
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| 27. |
- Luigi, Lorenzini, et al.
(författare)
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Gray matter network properties show distinct associations with CSF p-tau 181 levels and amyloid status in individuals without dementia.
- 2022
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Ingår i: Aging brain. - : Elsevier BV. - 2589-9589. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Gray matter networks are altered with amyloid accumulation in the earliest stage of AD, and are associated with decline throughout the AD spectrum. It remains unclear to what extent gray matter network abnormalities are associated with hyperphosphorylated-tau (p-tau). We studied the relationship of cerebrospinal fluid (CSF) p-tau181 with gray matter networks in non-demented participants from the European Prevention of Alzheimer's Dementia (EPAD) cohort, and studied dependencies on amyloid and cognitive status. Gray matter networks were extracted from baseline structural 3D T1w MRI. P-tau181 and abeta were measured with the Roche cobas Elecsys System. We studied the associations of CSF biomarkers levels with several network's graph properties. We further studied whether the relationships of p-tau 181 and network measures were dependent on amyloid status and cognitive stage (CDR). We repeated these analyses for network properties at a regional level, where we averaged local network values across cubes within each of 116 areas as defined by the automated anatomical labeling (AAL) atlas. Amyloid positivity was associated with higher network size and betweenness centrality, and lower gamma, clustering and small-world coefficients. Higher CSF p-tau 181 levels were related to lower betweenness centrality, path length and lambda coefficients (all p<0.01). Three-way interactions between p-tau181, amyloid status and CDR were found for path length, lambda and clustering (all p<0.05): Cognitively unimpaired amyloid-negative participants showed lower path length and lambda values with higher CSF p-tau181 levels. Amyloid-positive participants with impaired cognition demonstrated lower clustering coefficients in association to higher CSF p-tau181 levels. Our results suggest that alterations in gray matter network clustering coefficient is an early and specific event in AD.
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| 28. |
- Pan, Xiaobei, et al.
(författare)
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Plasma metabolites distinguish dementia with Lewy bodies from Alzheimer's disease: a cross-sectional metabolomic analysis
- 2024
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Ingår i: FRONTIERS IN AGING NEUROSCIENCE. - 1663-4365. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn multifactorial diseases, alterations in the concentration of metabolites can identify novel pathological mechanisms at the intersection between genetic and environmental influences. This study aimed to profile the plasma metabolome of patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), two neurodegenerative disorders for which our understanding of the pathophysiology is incomplete. In the clinical setting, DLB is often mistaken for AD, highlighting a need for accurate diagnostic biomarkers. We therefore also aimed to determine the overlapping and differentiating metabolite patterns associated with each and establish whether identification of these patterns could be leveraged as biomarkers to support clinical diagnosis.MethodsA panel of 630 metabolites (Biocrates MxP Quant 500) and a further 232 metabolism indicators (biologically informative sums and ratios calculated from measured metabolites, each indicative for a specific pathway or synthesis; MetaboINDICATOR) were analyzed in plasma from patients with probable DLB (n = 15; age 77.6 +/- 8.2 years), probable AD (n = 15; 76.1 +/- 6.4 years), and age-matched cognitively healthy controls (HC; n = 15; 75.2 +/- 6.9 years). Metabolites were quantified using a reversed-phase ultra-performance liquid chromatography column and triple-quadrupole mass spectrometer in multiple reaction monitoring (MRM) mode, or by using flow injection analysis in MRM mode. Data underwent multivariate (PCA analysis), univariate and receiving operator characteristic (ROC) analysis. Metabolite data were also correlated (Spearman r) with the collected clinical neuroimaging and protein biomarker data.ResultsThe PCA plot separated DLB, AD and HC groups (R2 = 0.518, Q2 = 0.348). Significant alterations in 17 detected metabolite parameters were identified (q <= 0.05), including neurotransmitters, amino acids and glycerophospholipids. Glutamine (Glu; q = 0.045) concentrations and indicators of sphingomyelin hydroxylation (q = 0.039) distinguished AD and DLB, and these significantly correlated with semi-quantitative measurement of cardiac sympathetic denervation. The most promising biomarker differentiating AD from DLB was Glu:lysophosphatidylcholine (lysoPC a 24:0) ratio (AUC = 0.92; 95%CI 0.809-0.996; sensitivity = 0.90; specificity = 0.90).DiscussionSeveral plasma metabolomic aberrations are shared by both DLB and AD, but a rise in plasma glutamine was specific to DLB. When measured against plasma lysoPC a C24:0, glutamine could differentiate DLB from AD, and the reproducibility of this biomarker should be investigated in larger cohorts.
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