| 1. |
- Barucca, G., et al.
(författare)
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Study of excited Ξ baryons with the P¯ ANDA detector
- 2021
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Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Tidskriftsartikel (refereegranskat)abstract
- The study of baryon excitation spectra provides insight into the inner structure of baryons. So far, most of the world-wide efforts have been directed towards N∗ and Δ spectroscopy. Nevertheless, the study of the double and triple strange baryon spectrum provides independent information to the N∗ and Δ spectra. The future antiproton experiment P¯ANDA will provide direct access to final states containing a Ξ¯ Ξ pair, for which production cross sections up to μb are expected in p¯p reactions. With a luminosity of L= 10 31 cm- 2 s- 1 in the first phase of the experiment, the expected cross sections correspond to a production rate of ∼106events/day. With a nearly 4 π detector acceptance, P¯ANDA will thus be a hyperon factory. In this study, reactions of the type p¯p → Ξ¯ +Ξ∗ - as well as p¯p → Ξ¯ ∗ +Ξ- with various decay modes are investigated. For the exclusive reconstruction of the signal events a full decay tree fit is used, resulting in reconstruction efficiencies between 3 and 5%. This allows high statistics data to be collected within a few weeks of data taking.
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| 2. |
- Barucca, G., et al.
(författare)
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The potential of Λ and Ξ- studies with PANDA at FAIR
- 2021
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Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Tidskriftsartikel (refereegranskat)abstract
- The antiproton experiment PANDA at FAIR is designed to bring hadron physics to a new level in terms of scope, precision and accuracy. In this work, its unique capability for studies of hyperons is outlined. We discuss ground-state hyperons as diagnostic tools to study non-perturbative aspects of the strong interaction, and fundamental symmetries. New simulation studies have been carried out for two benchmark hyperon-antihyperon production channels: p¯ p→ Λ¯ Λ and p¯ p→ Ξ¯ +Ξ-. The results, presented in detail in this paper, show that hyperon-antihyperon pairs from these reactions can be exclusively reconstructed with high efficiency and very low background contamination. In addition, the polarisation and spin correlations have been studied, exploiting the weak, self-analysing decay of hyperons and antihyperons. Two independent approaches to the finite efficiency have been applied and evaluated: one standard multidimensional efficiency correction approach, and one efficiency independent approach. The applicability of the latter was thoroughly evaluated for all channels, beam momenta and observables. The standard method yields good results in all cases, and shows that spin observables can be studied with high precision and accuracy already in the first phase of data taking with PANDA.
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| 3. |
- Sønderby, Ida E., et al.
(författare)
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1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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| 4. |
- van der Meer, Dennis, et al.
(författare)
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Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
- 2020
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
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| 5. |
- Sonderby, Ida E., et al.
(författare)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
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Tidskriftsartikel (refereegranskat)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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| 6. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 7. |
- Kuliński, Karol, et al.
(författare)
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Biogeochemical functioning of the Baltic Sea
- 2022
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Ingår i: Earth System Dynamics. - : Copernicus GmbH. - 2190-4979 .- 2190-4987. ; 13, s. 633-685
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Forskningsöversikt (refereegranskat)abstract
- Location, specific topography, and hydrographic setting together with climate change and strong anthropogenic pressure are the main factors shaping the biogeochemical functioning and thus also the ecological status of the Baltic Sea. The recent decades have brought significant changes in the Baltic Sea. First, the rising nutrient loads from land in the second half of the 20th century led to eutrophication and spreading of hypoxic and anoxic areas, for which permanent stratification of the water column and limited ventilation of deep-water layers made favourable conditions. Since the 1980s the nutrient loads to the Baltic Sea have been continuously decreasing. This, however, has so far not resulted in significant improvements in oxygen availability in the deep regions, which has revealed a slow response time of the system to the reduction of the land-derived nutrient loads. Responsible for that is the low burial efficiency of phosphorus at anoxic conditions and its remobilization from sediments when conditions change from oxic to anoxic. This results in a stoichiometric excess of phosphorus available for organic-matter production, which promotes the growth of N2-fixing cyanobacteria and in turn supports eutrophication. This assessment reviews the available and published knowledge on the biogeochemical functioning of the Baltic Sea. In its content, the paper covers the aspects related to changes in carbon, nitrogen, and phosphorus (C, N, and P) external loads, their transformations in the coastal zone, changes in organic-matter production (eutrophication) and remineralization (oxygen availability), and the role of sediments in burial and turnover of C, N, and P. In addition to that, this paper focuses also on changes in the marine CO2 system, the structure and functioning of the microbial community, and the role of contaminants for biogeochemical processes. This comprehensive assessment allowed also for identifying knowledge gaps and future research needs in the field of marine biogeochemistry in the Baltic Sea. Copyright:
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| 8. |
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| 9. |
- Amroussia, Nada, et al.
(författare)
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Do inequalities add up? : Intersectional inequalities in smoking by sexual orientation and education among U.S. adults
- 2020
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Ingår i: Preventive Medicine Reports. - : Elsevier. - 2211-3355. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Inequalities in smoking by socio-economic status (SES) are well-known. A growing body of literature has demonstrated additional inequalities in smoking by sexual orientation. This study used an intersectional lens to examine smoking at the intersection of sexual orientation and education.Methods: Data come from 28,362 adult participants in Wave 2 (2014–2015) of the Population Assessment of Tobacco and Health (PATH) Study. We used educational level (less than high school education (HS); HS or more) and sexual orientation (heterosexual; sexual minority) to form four intersectional positions.We estimated prevalence differences in smoking corresponding to joint, referent, and excess intersectional inequalities using weighted linear binomial regression models. Results were stratified by gender and adjusted for ethnicity and age.Results: The adjusted joint inequality represented 7.6% points (p.p.) (95% CI: 2.5, 12.8) difference in smoking between the doubly advantaged (heterosexual with HS or more) and doubly disadvantaged (sexual minority with less than HS) positions. Joint inequality was decomposed into referent SES inequality (12.5 p.p. (95% CI: 10.5, 14.4)); referent sexual orientation inequality (9.7 p.p. (95% CI: 6.8, 12.6)); and a substantial negative excess intersectional inequality (−14.6 p.p. (95% CI: −20.8, −8.3)), attributed to an unexpectedly low prevalence of smoking among doubly disadvantaged persons. Similar overall patterns were found in the stratified analyses.Conclusions: We found that “doubly-disadvantaged” group of low-educated sexual minority adults did not have the greatest burden of smoking; whereas, low-educated heterosexual adults had the highest smoking prevalence. Our findings support tailoring cessation interventions to disadvantaged groups’ different needs.
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| 10. |
- Anticona Huaynate, Cynthia, 1983-, et al.
(författare)
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Assessing inequities in unmet oral care needs among adults in Sweden : An intersectional approach
- 2023
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Ingår i: Community Dentistry and Oral Epidemiology. - : John Wiley & Sons. - 0301-5661 .- 1600-0528. ; 51:3, s. 428-435
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The goal of the Swedish oral healthcare system is to achieve good oral health and equitable access to care for the entire population. However, considerable inequities in oral health and care are evident and occur across a range of social dimensions. This study uses an intersectional approach to examine complex inequities in unmet oral care needs among adults in Sweden over the period 2004–2021.Methods: Data were obtained from 14 Health on Equal Terms surveys conducted during 2004–2021. The final sample was 129 473 individuals aged 26–84 years. Applying intersectional analysis of individual heterogeneity and discriminatory accuracy, inequities in unmet oral care needs were estimated across 48 intersectional strata defined by gender, age, educational level, individual disposable income and immigrant status.Results: A high risk of unmet oral care needs was found among strata consisting of immigrants and those with low income. However, being an immigrant and/or having a low income did not universally entail a high risk but varied by the social position along other axes, particularly age and education. The discriminatory accuracy was moderate.Conclusion: Groups with certain social disadvantages are highly heterogeneous themselves. An intersectionality approach is important to prevent the risk of stigmatizing large heterogenous groups while failing to identify the most vulnerable strata. The discriminatory accuracy analysis suggested that further policy and/or interventions may be the most effective if approaching the whole population, combined with selected targeted interventions directed at the most disadvantaged social strata.
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