| 1. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 3. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 4. |
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| 5. |
- Vogel, Jacob W., et al.
(author)
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Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
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Journal article (peer-reviewed)abstract
- Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 6. |
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| 7. |
- van Bragt, JJMH, et al.
(author)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Journal article (peer-reviewed)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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| 8. |
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| 9. |
- Bethlehem, RAI, et al.
(author)
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Brain charts for the human lifespan
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 604:7906, s. 525-
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Journal article (peer-reviewed)abstract
- Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
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| 17. |
- Pelletier, F., et al.
(author)
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Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C
- 2021
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In: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:2
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Journal article (peer-reviewed)abstract
- Context: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. Objective: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. Design: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. Setting: This was a multicenter retrospective study using information collected from 3 predominant centers. Patients: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. Main Outcome Measures: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. Results: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. Conclusions: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder.
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| 18. |
- Serge, M. A., et al.
(author)
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Testing the Effect of Relative Pollen Productivity on the REVEALS Model : A Validated Reconstruction of Europe-Wide Holocene Vegetation
- 2023
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In: Land. - : MDPI. - 2073-445X. ; 12:5
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Journal article (peer-reviewed)abstract
- Reliable quantitative vegetation reconstructions for Europe during the Holocene are crucial to improving our understanding of landscape dynamics, making it possible to assess the past effects of environmental variables and land-use change on ecosystems and biodiversity, and mitigating their effects in the future. We present here the most spatially extensive and temporally continuous pollen-based reconstructions of plant cover in Europe (at a spatial resolution of 1 degrees x 1 degrees) over the Holocene (last 11.7 ka BP) using the 'Regional Estimates of VEgetation Abundance from Large Sites' (REVEALS) model. This study has three main aims. First, to present the most accurate and reliable generation of REVEALS reconstructions across Europe so far. This has been achieved by including a larger number of pollen records compared to former analyses, in particular from the Mediterranean area. Second, to discuss methodological issues in the quantification of past land cover by using alternative datasets of relative pollen productivities (RPPs), one of the key input parameters of REVEALS, to test model sensitivity. Finally, to validate our reconstructions with the global forest change dataset. The results suggest that the RPPs.st1 (31 taxa) dataset is best suited to producing regional vegetation cover estimates for Europe. These reconstructions offer a long-term perspective providing unique possibilities to explore spatial-temporal changes in past land cover and biodiversity.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Dennis, J, et al.
(author)
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Rare germline copy number variants (CNVs) and breast cancer risk
- 2022
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 65-
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Journal article (peer-reviewed)abstract
- Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E−18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.
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| 25. |
- Park, J, et al.
(author)
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Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:10
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Journal article (peer-reviewed)abstract
- In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
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| 26. |
- Stacchiotti, S., et al.
(author)
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Epithelioid hemangioendothelioma, an ultra-rare cancer : a consensus paper from the community of experts
- 2021
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In: ESMO Open. - : Elsevier BV. - 2059-7029. ; 6:3
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Research review (peer-reviewed)abstract
- Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.
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| 27. |
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| 28. |
- Bockelee-Morvan, D., et al.
(author)
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Composition and thermal properties of Ganymede's surface from JWST/NIRSpec and MIRI observations
- 2024
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 681, s. A27-
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Journal article (peer-reviewed)abstract
- Context. We present the first spectroscopic observations of Ganymede by the James Webb Space Telescope undertaken in August 2022 as part of the proposal "ERS observations of the Jovian system as a demonstration of JWST's capabilities for Solar System science".Aims. We aimed to investigate the composition and thermal properties of the surface, and to study the relationships of ice and non-water-ice materials and their distribution.Methods. NIRSpec IFU (2.9-5.3 mu m) and MIRI MRS (4.9-28.5 mu m) observations were performed on both the leading and trailing hemispheres of Ganymede, with a spectral resolution of similar to 2700 and a spatial sampling of 0.1 to 0.17 '' (while the Ganymede size was similar to 1.68 ''). We characterized the spectral signatures and their spatial distribution on the surface. The distribution of brightness temperatures was analyzed with standard thermophysical modeling including surface roughness.Results. Reflectance spectra show signatures of water ice, CO2, and H2O2. An absorption feature at 5.9 mu m, with a shoulder at 6.5 mu m, is revealed, and is tentatively assigned to sulfuric acid hydrates. The CO2 4.26-mu m band shows latitudinal and longitudinal variations in depth, shape, and position over the two hemispheres, unveiling different CO2 physical states. In the ice-rich polar regions, which are the most exposed to Jupiter's plasma irradiation, the CO2 band is redshifted with respect to other terrains. In the boreal region of the leading hemisphere, the CO2 band is dominated by a high wavelength component at similar to 4.27 mu m, consistent with CO2 trapped in amorphous water ice. At equatorial latitudes (and especially on dark terrains), the observed band is broader and shifted toward the blue, suggesting CO2 adsorbed on non-icy materials, such as minerals or salts. Maps of the H2O Fresnel peak area correlate with Bond albedo maps and follow the distribution of water ice inferred from H2O absorption bands. Amorphous ice is detected in the ice-rich polar regions, and is especially abundant on the northern polar cap of the leading hemisphere. Leading and trailing polar regions exhibit different H2O, CO2, and H2O2 spectral properties. However, in both hemispheres the north polar cap ice appears to be more processed than the south polar cap. A longitudinal modification of the H2O ice molecular structure and/or nanometer- and micrometer-scale texture, of diurnal or geographic origin, is observed in both hemispheres. Ice frost is tentatively observed on the morning limb of the trailing hemisphere, which possibly formed during the night from the recondensation of water subliming from the warmer subsurface. Reflectance spectra of the dark terrains are compatible with the presence of Na- and Mg-sulfate salts, sulfuric acid hydrates, and possibly phyllosilicates mixed with fine-grained opaque minerals, with a highly porous texture. Latitude and local time variations of the brightness temperatures indicate a rough surface with mean slope angles of 15 degrees-25 degrees and a low thermal inertia Gamma = 20 - 40 J m(-2) s(-0.5) K-1, consistent with a porous surface, with no obvious difference between the leading and trailing sides.
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| 29. |
- DeWitt, Jamie C., et al.
(author)
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Zürich II Statement on Per- and Polyfluoroalkyl Substances (PFASs) : Scientific and Regulatory Needs
- 2024
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In: Environmental Science and Technology Letters. - 2328-8930. ; 11:8, s. 786-797
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Research review (peer-reviewed)abstract
- Per- and polyfluoroalkyl substances (PFASs) are a class of synthetic organic chemicals of global concern. A group of 36 scientists and regulators from 18 countries held a hybrid workshop in 2022 in Zürich, Switzerland. The workshop, a sequel to a previous Zürich workshop held in 2017, deliberated on progress in the last five years and discussed further needs for cooperative scientific research and regulatory action on PFASs. This review reflects discussion and insights gained during and after this workshop and summarizes key signs of progress in science and policy, ongoing critical issues to be addressed, and possible ways forward. Some key take home messages include: 1) understanding of human health effects continues to develop dramatically, 2) regulatory guidelines continue to drop, 3) better understanding of emissions and contamination levels is needed in more parts of the world, 4) analytical methods, while improving, still only cover around 50 PFASs, and 5) discussions of how to group PFASs for regulation (including subgroupings) have gathered momentum with several jurisdictions proposing restricting a large proportion of PFAS uses. It was concluded that more multi-group exchanges are needed in the future and that there should be a greater diversity of participants at future workshops.
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| 30. |
- Ebel, Matilda, et al.
(author)
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Gestational hypertension, preeclampsia, and gestational diabetes mellitus after high exposure to perfluoroalkyl substances from drinking water in Ronneby, Sweden
- 2023
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In: Environmental Research. - 0013-9351. ; 239
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Journal article (peer-reviewed)abstract
- Background: Leakage of fire-fighting foam from an airfield caused contamination of the drinking water supplied to a third of the population in Ronneby, resulting in very high serum levels of predominantly perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS). The results of studies investigating the association between exposure to perfluorinated alkyl substances (PFAS) and pregnancy complications are inconsistent, and studies at high exposures of PFOS and PFHxS are lacking. Objectives: To investigate the association between exposure to high levels of PFAS and gestational hypertension and preeclampsia, and gestational diabetes mellitus. Methods: We retrieved data on 27 292 childbirths between 1995 and 2013 from the National Medical Birth Register for women that had a residential address in Blekinge county for at least one year before delivery. Residential history was used as a proxy for exposure by categorizing women into high-, intermediate-, or background exposed based on their residential address during the five-year period before childbirth. Data on confounders were retrieved from administrative registers. The outcomes were defined based on International Classification of Diseases codes. We used logistic regression to estimate odds ratios (OR) for gestational hypertension and preeclampsia, and gestational diabetes mellitus. We also investigated effect modification by fetal sex. Results: We found no evidence of increased risk of gestational hypertension and preeclampsia (OR 0.80; CI 0.63-1.03), nor gestational diabetes (OR 1.03; CI 0.67-1.58) after high PFAS exposure. There was no effect modification by fetal sex. Discussion: This was the first study to investigate the association between high exposure to PFOS and PFHxS and pregnancy complications. The results from this study add important knowledge to public health management as new hotspots with high levels of PFAS are continuously discovered.
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| 31. |
- Fazey, Ioan, et al.
(author)
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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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In: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Journal article (peer-reviewed)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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| 32. |
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| 33. |
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| 34. |
- Grant, Michael C., et al.
(author)
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Perioperative Care in Cardiac Surgery : A Joint Consensus Statement by the Enhanced Recovery After Surgery (ERAS) Cardiac Society, ERAS International Society, and The Society of Thoracic Surgeons (STS)
- 2024
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In: Annals of Thoracic Surgery. - : Elsevier. - 0003-4975 .- 1552-6259. ; 117:4, s. 669-689
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Journal article (peer-reviewed)abstract
- Enhanced Recovery After Surgery (ERAS) programs have been shown to lessen surgical insult, promote recovery, and improve postoperative clinical outcomes across a number of specialty operations. A core tenet of ERAS involves the provision of protocolized evidence-based perioperative interventions. Given both the growing enthusiasm for applying ERAS principles to cardiac surgery and the broad scope of relevant interventions, an international, multidisciplinary expert panel was assembled to derive a list of potential program elements, review the literature, and provide a statement regarding clinical practice for each topic area. This article summarizes those consensus statements and their accompanying evidence. These results provide the foundation for best practice for the management of the adult patient undergoing cardiac surgery.
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| 35. |
- Huang, S., et al.
(author)
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Systematic review and literature appraisal on methodology of conducting and reporting critical-care echocardiography studies: a report from the European Society of Intensive Care Medicine PRICES expert panel
- 2020
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In: Annals of Intensive Care. - : SPRINGER. - 2110-5820. ; 10:1
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Research review (peer-reviewed)abstract
- Background The echocardiography working group of the European Society of Intensive Care Medicine recognized the need to provide structured guidance for future CCE research methodology and reporting based on a systematic appraisal of the current literature. Here is reported this systematic appraisal. Methods We conducted a systematic review, registered on the Prospero database. A total of 43 items of common interest to all echocardiography studies were initially listed by the experts, and other "topic-specific" items were separated into five main categories of interest (left ventricular systolic function, LVSF n = 15, right ventricular function, RVF n = 18, left ventricular diastolic function, LVDF n = 15, fluid management, FM n = 7, and advanced echocardiography techniques, AET n = 17). We evaluated the percentage of items reported per study and the fraction of studies reporting a single item. Results From January 2000 till December 2017 a total of 209 articles were included after systematic search and screening, 97 for LVSF, 48 for RVF, 51 for LVDF, 36 for FM and 24 for AET. Shock and ARDS were relatively common among LVSF articles (both around 15%) while ARDS comprised 25% of RVF articles. Transthoracic echocardiography was the main echocardiography mode, in 87% of the articles for AET topic, followed by 81% for FM, 78% for LVDF, 70% for LVSF and 63% for RVF. The percentage of items per study as well as the fraction of study reporting an item was low or very low, except for FM. As an illustration, the left ventricular size was only reported by 56% of studies in the LVSF topic, and half studies assessing RVF reported data on pulmonary artery systolic pressure. Conclusion This analysis confirmed sub-optimal reporting of several items listed by an expert panel. The analysis will help the experts in the development of guidelines for CCE study design and reporting.
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| 36. |
- Kaya, Ibrahim, et al.
(author)
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Brain region-specific amyloid plaque-associated myelin lipid loss, APOE deposition and disruption of the myelin sheath in familial Alzheimer's disease mice
- 2020
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In: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 154:1, s. 84-98
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Journal article (peer-reviewed)abstract
- There is emerging evidence that amyloid beta (A beta) aggregates forming neuritic plaques lead to impairment of the lipid-rich myelin sheath and glia. In this study, we examined focal myelin lipid alterations and the disruption of the myelin sheath associated with amyloid plaques in a widely used familial Alzheimer's disease (AD) mouse model; 5xFAD. This AD mouse model has A beta(42) peptide-rich plaque deposition in the brain parenchyma. Matrix-assisted laser desorption/ionization imaging mass spectrometry of coronal brain tissue sections revealed focal A beta plaque-associated depletion of multiple myelin-associated lipid species including sulfatides, galactosylceramides, and specific plasmalogen phopshatidylethanolamines in the hippocampus, cortex, and on the edges of corpus callosum. Certain phosphatidylcholines abundant in myelin were also depleted in amyloid plaques on the edges of corpus callosum. Further, lysophosphatidylethanolamines and lysophosphatidylcholines, implicated in neuroinflammation, were found to accumulate in amyloid plaques. Double staining of the consecutive sections with fluoromyelin and amyloid-specific antibody revealed amyloid plaque-associated myelin sheath disruption on the edges of the corpus callosum which is specifically correlated with plaque-associated myelin lipid loss only in this region. Further, apolipoprotein E, which is implicated in depletion of sulfatides in AD brain, is deposited in all the A beta plaques which suggest apolipoprotein E might mediate sulfatide depletion as a consequence of an immune response to A beta deposition. This high-spatial resolution matrix-assisted laser desorption/ionization imaging mass spectrometry study in combination with (immuno) fluorescence staining of 5xFAD mouse brain provides new understanding of morphological, molecular and immune signatures of A beta plaque pathology-associated myelin lipid loss and myelin degeneration in a brain region-specific manner.
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| 37. |
- Lenk, E. J., et al.
(author)
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A Test-and-Not-Treat Strategy for Onchocerciasis Elimination in Loa loa-coendemic Areas : Cost Analysis of a Pilot in the Soa Health District, Cameroon
- 2020
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In: Clinical Infectious Diseases. - : NLM (Medline). - 1058-4838 .- 1537-6591. ; 70:8, s. 1628-1635
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Journal article (peer-reviewed)abstract
- BACKGROUND: Severe adverse events after treatment with ivermectin in individuals with high levels of Loa loa microfilariae in the blood preclude onchocerciasis elimination through community-directed treatment with ivermectin (CDTI) in Central Africa. We measured the cost of a community-based pilot using a test-and-not-treat (TaNT) strategy in the Soa health district in Cameroon. METHODS: Based on actual expenditures, we empirically estimated the economic cost of the Soa TaNT campaign, including financial costs and opportunity costs that will likely be borne by control programs and stakeholders in the future. In addition to the empirical analyses, we estimated base-case, less intensive, and more intensive resource use scenarios to explore how costs might differ if TaNT were implemented programmatically. RESULTS: The total costs of US$283 938 divided by total population, people tested, and people treated with 42% coverage were US$4.0, US$9.2, and US$9.5, respectively. In programmatic implementation, these costs (base-case estimates with less and more intensive scenarios) could be US$2.2 ($1.9-$3.6), US$5.2 ($4.5-$8.3), and US$5.4 ($4.6-$8.6), respectively. CONCLUSIONS: TaNT clearly provides a safe strategy for large-scale ivermectin treatment and overcomes a major obstacle to the elimination of onchocerciasis in areas coendemic for Loa loa. Although it is more expensive than standard CDTI, costs vary depending on the setting, the implementation choices made by the institutions involved, and the community participation rate. Research on the required duration of TaNT is needed to improve the affordability assessment, and more experience is needed to understand how to implement TaNT optimally.
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| 38. |
- Li, Huiqi, et al.
(author)
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Cancer incidence in a Swedish cohort with high exposure to perfluoroalkyl substances in drinking water
- 2022
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In: Environmental Research. - : Elsevier BV. - 0013-9351. ; 204:Part C
-
Journal article (peer-reviewed)abstract
- Background: The use of firefighting foams at a military airport resulted in high levels of perfluorinated substances (PFAS) in the drinking water distributed to one-third of households in the Swedish municipality of Ronneby between the mid-1980s and the end of 2013. Method: The Ronneby Register Cohort, a large cohort comprising all individuals (N = 60,507) who ever lived in the Ronneby municipality during the period of drinking water contamination, was linked to the Swedish Cancer Register 1985-2016. Individual exposure was classified based on comprehensive data on yearly residential address and water distribution. External analysis explored standardized cancer incidence ratios (SIR) for residents never, or ever, residing in the contaminated water district, compared with those residing in other towns in the same county as reference population. Cox models provided hazard ratios (HR) for different exposure groups within the cohort. Results: 5,702 individuals with cancer were identified. SIR for overall cancer was 1.04 for men (95%CI 0.96-1.12) and 0.89 for women (95%CI 0.82-0.96) who ever lived in the contaminated drinking water area. Kidney cancer, which was reported with increased risk in C8 study, showed somewhat elevated HR in this study (HR 1.27; 95%CI 0.85-1.89). The HR was modestly elevated for bladder cancer (HR 1.32; 95%CI 1.01-1.72), and reduced for prostate cancer (HR 0.83; 95%CI 0.71-0.98). In subjects who ever lived in the contaminated water area during 2005-2013, when exposure was estimated to be highest, higher risks for kidney cancer (HR 1.84; 95%CI 1.00-3.37) but lower for prostate cancer (HR 0.76; 95%CI 0.59-0.98) were observed. Conclusion: Analysis of this large cohort exposed to high levels of PFAS, dominated by PFHxS and PFOS, revealed no evidence for an overall increased risk of cancer. A moderately increased risk of kidney cancer was observed, in accordance with previous findings after PFAS exposure dominated by PFOA.
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| 39. |
- Li, Ying, et al.
(author)
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Associations between perfluoroalkyl substances and serum lipids in a Swedish adult population with contaminated drinking water
- 2020
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In: Environmental health. - : Springer Science and Business Media LLC. - 1476-069X. ; 19:1
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Journal article (peer-reviewed)abstract
- Background Exposures to perfluoroalkyl substances (PFAS) have shown positive associations with serum lipids in previous studies. While many studies on lipids investigated associations with perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), there are only a few studies regarding other PFAS, such as perfluorohexane sulfonic acid (PFHxS). The purpose of the current study is to investigate if associations with serum lipids were present, not only for serum PFOS and PFOA, but also for PFHxS, and if the associations with PFAS remained also in a comparison based only on residency in areas with contrasting exposure to PFAS. Methods 1945 adults aged 20-60 were included from Ronneby, Sweden, a municipality where one out of two waterworks had been heavily contaminated from aqueous fire-fighting foams, and from a nearby control area. The exposure was categorized based on either been living in areas with contrasting PFAS exposure or based on the actual serum PFAS measurements. Regression analyses of serum lipids were fitted against serum PFAS levels, percentile groups, smooth splines and between exposed and reference areas, adjusting for age, sex and BMI. Results Drinking water contamination caused high serum levels of PFOS (median 157 ng/ml) and PFHxS (median 136 ng/ml) and PFOA (median 8.6 ng/ml). These serum PFAS levels in the exposed groups were 5 to 100-fold higher than in the controls. In this population with mixed PFAS exposure, predominantly PFOS and PFHxS, PFAS exposure were positively associated with serum lipids. This was observed both when quantifying exposure as contrast between exposed and controls, and in terms of serum PFAS. Due to high correlations between each PFAS, we cannot separate them. Conclusions In conclusion, the present study provides further evidence of a causal association between PFAS and serum lipids, especially for PFHxS.
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| 40. |
- Li, Ying, et al.
(author)
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Determinants of serum half-lives for linear and branched perfluoroalkyl substances after long-term high exposure-A study in Ronneby, Sweden
- 2022
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In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 163
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Journal article (peer-reviewed)abstract
- Background: Per-and polyfluoroalkyl substances (PFAS) are persistent substances with surfactant and repellent properties. Municipal drinking water contaminated with PFAS had been distributed for decades to one third of households in Ronneby, Sweden. The source was firefighting foam used in a nearby airfield since the mid-1980s. Clean water was provided from December 16, 2013. Aims: The purpose was to estimate serum half-lives and their determinants in the study population for different PFAS. Methods: Up to ten blood samples were collected between 2014 and 2018 from 114 participants (age 4-84 years at entry, 53% female). 19 PFAS were analysed. Linear mixed models were used to estimate the half-lives. Results: Eight PFAS were increased in Ronneby: perfluorooctanoic acid (PFOA), perfluoropentane sulfonate (PFPeS), perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), linear perfluorooctane sulfonate (L-PFOS) and three branched perfluorooctane sulfonates (1 m-PFOS, 3/4/5m-PFOS and 2/6m-PFOS). The mean estimated half-lives (in years) were 0.94 (95 %CI 0.86-1.02) for PFPeS, 2.47 (2.27-2.7) for PFOA, 2.67 (2.51-2.85) for 2/6m-PFOS, 2.73 (2.55-2.92) for L-PFOS, 3.43 (3.19-3.71) for 3/4/5m-PFOS, 4.52 (4.14-4.99) for PFHxS, 4.55 (4.14-5.06) for PFHpS, and 5.01 (4.56-5.55) for 1 m-PFOS. The most important determinants of a shorter half-life were young age, and better kidney function measured by estimated glomerular filtration rate and ratio of paired urine and serum PFAS levels, followed by female sex during their fertile period aged 15-50. Markers of gut inflammation and reduced permeability i.e. zonulin and calprotectin were also possibly associated with shorter half-life. The results also suggested a time-dependent PFAS elimination process, with more rapid elimination in the first year after the end of exposure. Conclusion: The half-life estimates are in line with past estimates for some PFAS such as PFOA, and the novel results for different PFOS isomers. These results provide observational support for elimination routes - renal, fecal and maternal.
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| 41. |
- Ma, M., et al.
(author)
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Preface
- 2020
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In: 6th Joint International Conference on Serious Games, JCSG 2020. - : Springer Science and Business Media Deutschland GmbH.
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Conference paper (peer-reviewed)
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| 42. |
- Middha, Pooja K., et al.
(author)
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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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In: Breast Cancer Research. - : BioMed Central (BMC). - 1465-5411 .- 1465-542X. ; 25:1
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Journal article (peer-reviewed)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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| 43. |
- Naehrlich, L., et al.
(author)
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Incidence of SARS-CoV-2 in people with cystic fibrosis in Europe between February and June 2020
- 2021
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In: Journal of Cystic Fibrosis. - : Elsevier BV. - 1569-1993. ; 20:4, s. 566-577
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Journal article (peer-reviewed)abstract
- Background: Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). Methods: We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. Results: Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/10 0 0 pwCF. Incidence was higher in lung-transplanted patients (n = 23) versus non transplanted patients (n = 107) (8.43 versus 2.36 cases/10 0 0). Incidence was higher in pwCF versus the age-matched general population in the age groups < 15, 15-24, and 25-49 years (p < 0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p = 0.133). Conclusions: SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
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| 44. |
- Nielsen, Christel, et al.
(author)
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Breastfeeding initiation and duration after high exposure to perfluoroalkyl substances through contaminated drinking water: A cohort study from Ronneby, Sweden
- 2022
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In: Environmental Research. - : Elsevier BV. - 0013-9351. ; 207
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Journal article (peer-reviewed)abstract
- Background: The drinking water in parts of Ronneby was heavily contaminated with perfluoroalkyl substances (PFAS) for decades. Although PFAS has endocrine-disrupting properties and may interfere with breastfeeding, the effects in populations with a point source of high exposure are unknown. Objectives: To investigate associations between high PFAS exposure and 1) initiation and 2) duration of breastfeeding. Methods: We retrieved data on infant feeding practices for 2374 children born between 1999 and 2009 from Child Health Care centers in Ronneby and a reference municipality. Residential address before delivery was used as a proxy for exposure, and confounders were obtained from charts and registers. We used modified Poisson regressions to estimate the relative risks (RR) of not initiating breastfeeding, not breastfeeding exclusively after 3 months, and not breastfeeding at all at 6 months. We also estimated hazard ratios (HR) of cessation of exclusive breastfeeding before 6 months and any breastfeeding before 12 months. Results: Mothers who had received contaminated water seemed to have a higher risk of not initiating breastfeeding (RR = 2.4; 95% CI: 0.8, 6.7). Primiparous mothers from the exposed area were at a 1.2 times increased risk (95% CI: 0.9, 1.6) of not exclusively breastfeeding at 3 months and a 1.6 times increased risk (95% CI: 1.2, 2.1) of not breastfeeding at 6 months. The results were confirmed by the Cox regressions, which further showed that the HR for cessation of any breastfeeding was time dependent and higher in early lactation, thereafter decreasing as lactation progressed. We observed no overall associations in multiparous mothers. Discussion: Exposure to high levels of PFAS seemed to be associated with increased risks of not initiating breastfeeding and shorter breastfeeding duration in primiparous mothers. The findings imply that the ability of first-time mothers to establish breastfeeding is a sensitive outcome after high exposure to PFAS.
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| 45. |
- Pettersson-Segerlind, J, et al.
(author)
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Health-Related Quality of Life and Return to Work after Surgery for Spinal Meningioma: A Population-Based Cohort Study
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:24
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Journal article (peer-reviewed)abstract
- Spinal meningiomas are the most common primary spinal intradural tumor. This study aimed to assess Health-related quality of life (HRQoL) and the frequency of return to work in patients surgically treated for spinal meningiomas, in comparison to the general population. Variables were collected from patient charts, EQ-5D-3L, and study specific questionnaires. Patients who had been operated between 2005–2017 were identified in a previous study and those alive in 2020 (104 of 129) were asked to participate. Eighty-four patients (80.8%) with a mean follow-up of 8.7 years, responded and were included. Data was compared to the Stockholm Public Health Survey 2006, a cross-sectional survey of a representative sample of the general population. Analysis for potential non-response bias showed no significant differences. Women in the meningioma sample scored more problems than men with regards to mobility (p = 0.048). There were no significant differences concerning EQ-5Dindex (p = 0.325) or EQVAS (p = 0.116). The correlation between follow-up time and EQ-5Dindex was low (r = 0.167). When comparing HRQoL to the general population sample, no significant differences were found within the EQ-5D-3L dimensions, EQ-5Dindex or EQVAS. Those who postoperatively scored 3–5 on mMCs scored significantly more problems in the EQ-5D-3L dimension mobility (p = 0.023). Before surgery, 41 (48.8%) of the spinal meningioma patients were working and after surgery all returned to work, the majority within three months. Seventy-eight (96%) of the patients would accept surgery for the same diagnosis if asked today. We conclude that surgery for spinal meningiomas is associated with good long-term HRQoL and a high frequency of return to work.
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| 46. |
- Pettersson-Segerlind, J, et al.
(author)
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Long-Term Follow-Up and Predictors of Functional Outcome after Surgery for Spinal Meningiomas: A Population-Based Cohort Study
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:13
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Journal article (peer-reviewed)abstract
- Spinal meningiomas are the most common adult primary spinal tumor, constituting 24–45% of spinal intradural tumors and 2% of all meningiomas. The aim of this study was to assess postoperative complications, long-term outcomes, predictors of functional improvement and differences between elderly (≥70 years) and non-elderly (18–69 years) patients surgically treated for spinal meningiomas. Variables were retrospectively collected from patient charts and magnetic resonance images. Baseline comparisons, paired testing and regression analyses were used. In conclusion, 129 patients were included, with a median follow-up time of 8.2 years. Motor deficit was the most common presenting symptom (66%). The median time between diagnosis and surgery was 1.3 months. A postoperative complication occurred in 10 (7.8%) and tumor growth or recurrence in 6 (4.7%) patients. Surgery was associated with significant improvement of motor and sensory deficit, gait disturbance, bladder dysfunction and pain. Time to surgery, tumor area and the degree of spinal cord compression significantly predicted postoperative improvement in a modified McCormick scale (mMCs) in the univariable regression analysis, and spinal cord compression showed independent risk association in multivariable analysis. There was no difference in improvement, complications or tumor control between elderly and non-elderly patients. We concluded that surgery of spinal meningiomas was associated with significant long-term neurological improvement, which could be predicted by time to surgery, tumor size and spinal cord compression.
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| 47. |
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| 48. |
- Pettersson-Segerlind, J, et al.
(author)
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Long-Term Follow-Up, Treatment Strategies, Functional Outcome, and Health-Related Quality of Life after Surgery for WHO Grade 2 and 3 Intracranial Meningiomas
- 2022
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In: Cancers. - : MDPI AG. - 2072-6694. ; 14:20
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Journal article (peer-reviewed)abstract
- Progression-free survival (PFS) and overall survival (OS) for WHO grade 2 and 3 intracranial meningiomas are poorly described, and long-term results and data evaluating the routine use of supplementary fractionated radiotherapy (RT) or stereotactic radiosurgery (SRS) has been inconclusive. The aim of this study was to determine the long-term PFS and OS at a center that does not employ routine adjuvant RT. For this purpose, a retrospective population-based cohort study was conducted of all WHO grade 2 and 3 meningiomas surgically treated between 2005 and 2013. The cohort was uniformly defined according to the WHO 2007 criteria to allow comparisons to previously published reports. Patient records were reviewed, and patients were then prospectively contacted for structured quality-of-life assessments. In total, 51 consecutive patients were included, of whom 43 were WHO grade 2 and 8 were grade 3. A Simpson grade 1–2 resection was achieved in 62%. The median PFS was 31 months for grade 2 tumors, and 3.4 months for grade 3. The median OS was 13 years for grade 2, and 1.4 years for grade 3. The MIB-1-index was significantly associated with an increased risk for recurrence (p = 0.018, OR 1.12). The median PFS was significantly shorter for high-risk tumors compared to the low-risk group (10 vs. 46 months; p = 0.018). The surviving meningioma patients showed HRQoL measures comparable to that of the general population, with the exception of significantly more anxiety and depression. All patients who worked before surgery returned to work after their treatment. In conclusion, we confirm dismal prognoses in patients with grade 2 and 3 meningiomas, with tumor-related deaths resulting in severely reduced OS. However, the cohort was heterogenous, and a large subgroup of both grade 2 and 3 meningiomas was alive at 10 years follow-up, suggesting that a cure is possible. In addition, fractionated radiotherapy and chemotherapy had little benefit when introduced for recurrent and progressive diseases.
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| 49. |
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| 50. |
- Pietilä, Riikka, et al.
(author)
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Molecular anatomy of adult mouse leptomeninges
- 2023
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In: Neuron. - : Elsevier. - 0896-6273 .- 1097-4199. ; 111:23
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Journal article (peer-reviewed)abstract
- Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we iden-tify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arach-noid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology.
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