| 1. |
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| 2. |
- Gao, YX, et al.
(author)
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Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
- 2020
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 12184-
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Journal article (peer-reviewed)abstract
- We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.
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| 10. |
- 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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| 12. |
- Ahlström, Gerd, et al.
(author)
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Quality of Life among Next of Kin of Frail Older People in Nursing Homes : An Interview Study after an Educational Intervention concerning Palliative Care
- 2022
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In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 19:5
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Journal article (peer-reviewed)abstract
- One cornerstone of palliative care is improving the family’s quality of life (QoL). The principles of palliative care have not been sufficiently applied in nursing homes. The aim of this study was to investigate the experiences of QoL of next of kin of frail older persons in nursing homes after an educational intervention concerning palliative care. This qualitative interview study with 37 next of kin used an abductive design with deductive and inductive content analysis. The deductive analysis confirmed the three themes of QoL from the study before the implementation: (1) orientation to the new life-situation, (2) challenges in the relationship, and (3) the significance of the quality of care in the nursing home. The inductive analysis resulted in the sub-theme “Unspoken palliative care”. Being the next of kin of an older person living in a nursing home can be distressing despite round-the-clock care, so staff need to apply a more explicitly palliative care perspective. Future research needs to evaluate the influence of meaning-focused coping on next of kin’s QoL and integrate this knowledge in psychosocial interventions. Clinical Trial Database for Clinical Research: KUPA project NCT02708498.
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| 13. |
- Bergstedt, Edwin, 1986-
(author)
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A Comparative Investigation of Gear Performance BetweenWrought and Sintered Powder Metallurgical Steel : Utilizing In-situ Surface Profile Measurements to Investigate theInitiation and Evolution of Micropitting and Pitting Damage
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Vehicle electrification is a strong trend that introduces new challenges, such as increased input speed of the transmission and increased power density. Alsothe noise emittance of the gearbox is of increasing importance, as the sound of the gearbox is no longer masked by the internal combustion engine. Pressed and sintered powder metallurgical steel could be an interesting alternative towrought steel; the internal porosity has a dampening effect on the noise, and gears can be made in a fast and efficient process. However, current manufacturing of powder metallurgical steel has significant performance limitations. The Nanotechnology Enhanced Sintered Steel Processing project aims to reduce the gap in performance between conventional steel and powder metallurgical steel. One of the potential benefits is that with the inclusion of nano-powder the density can be increased. To validate the new material, its performance needs to be compared to the performance of current generation powder metallurgical materials and also to wrought steel. It is therefor crucial to be able to test and evaluate different materials and gears. This thesis has developed methods for testing, comparing, and evaluating the performance of gears. Powder metallurgical steel has been tested and compared to wrought steel; the efficiency as well as pitting life have been investigated in an FZG test rig. Also the effects of different surface finishing operations have been evaluated. The gear flanks were measured in-situ in the gearbox using a stylus instrument; an optimisation routine was created to fit the measurements to the theoretical involute profile. This enabled an in-depth analysis of surface wear and presented an opportunity to investigate micropitting initiation. It was found that the damage mechanisms of wrought steel and powder metallurgical steel are similar and related to the surface finishing method. However, the powder metallurgical steel was also susceptible to sub-surface cracks. Superfinished gears can be negatively influenced by the lack of tip relief as cracks initiate in the surface layer of the root, rapidly destroying the tooth.
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| 14. |
- Bocancea, Diana I., et al.
(author)
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Determinants of cognitive and brain resilience to tau pathology: a longitudinal analysis
- 2023
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 146:9, s. 3719-3734
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Journal article (peer-reviewed)abstract
- Mechanisms of resilience against tau pathology in individuals across the Alzheimer’s disease spectrum are insufficiently understood. Longitudinal data are necessary to reveal which factors relate to preserved cognition (i.e. cognitive resilience) and brain structure (i.e. brain resilience) despite abundant tau pathology, and to clarify whether these associations are cross-sectional or longitudinal. We employed a longitudinal study design to investigate the role of several demographic, biological and brain structural factors in yielding cognitive and brain resilience to tau pathology as measured with PET.In this multicenter study, we included 366 amyloid-β-positive individuals with mild cognitive impairment or Alzheimer’s disease-dementia with baseline [18F]flortaucipir-PET and longitudinal cognitive assessments. A subset (n = 200) additionally underwent longitudinal structural MRI. We used linear mixed-effects models with global cognition and cortical thickness as dependent variables to investigate determinants of cognitive resilience and brain resilience, respectively. Models assessed whether age, sex, years of education, APOE-ε4 status, intracranial volume (and cortical thickness for cognitive resilience models) modified the association of tau pathology with cognitive decline or cortical thinning.We found that the association between higher baseline tau-PET levels (quantified in a temporal meta-region of interest) and rate of cognitive decline (measured with repeated Mini-Mental State Examination) was adversely modified by older age (Stβinteraction = -0.062, P = 0.032), higher education level (Stβinteraction = -0.072, P = 0.011) and higher intracranial volume (Stβinteraction = -0.07, P = 0.016). Younger age, higher education and greater cortical thickness were associated with better cognitive performance at baseline. Greater cortical thickness was furthermore associated with slower cognitive decline independent of tau burden. Higher education also modified the negative impact of tau-PET on cortical thinning, while older age was associated with higher baseline cortical thickness and slower rate of cortical thinning independent of tau. Our analyses revealed no (cross-sectional or longitudinal) associations for sex and APOE-ε4 status on cognition and cortical thickness.In this longitudinal study of clinically impaired individuals with underlying Alzheimer’s disease neuropathological changes, we identified education as the most robust determinant of both cognitive and brain resilience against tau pathology. The observed interaction with tau burden on cognitive decline suggests that education may be protective against cognitive decline and brain atrophy at lower levels of tau pathology, with a potential depletion of resilience resources with advancing pathology. Finally, we did not find major contributions of sex to brain nor cognitive resilience, suggesting that previous links between sex and resilience might be mainly driven by cross-sectional differences.
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| 16. |
- Chastin, Sebastien, et al.
(author)
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Joint association between accelerometry-measured daily combination of time spent in physical activity, sedentary behaviour and sleep and all-cause mortality : A pooled analysis of six prospective cohorts using compositional analysis
- 2021
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In: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 55:22, s. 1277-1285
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To examine the joint associations of daily time spent in different intensities of physical activity, sedentary behaviour and sleep with all-cause mortality.METHODS: Federated pooled analysis of six prospective cohorts with device-measured time spent in different intensities of physical activity, sedentary behaviour and sleep following a standardised compositional Cox regression analysis.PARTICIPANTS: 130 239 people from general population samples of adults (average age 54 years) from the UK, USA and Sweden.MAIN OUTCOME: All-cause mortality (follow-up 4.3-14.5 years).RESULTS: Studies using wrist and hip accelerometer provided statistically different results (I2=92.2%, Q-test p<0.001). There was no association between duration of sleep and all-cause mortality, HR=0.96 (95% CI 0.67 to 1.12). The proportion of time spent in moderate to vigorous physical activity was significantly associated with lower risk of all-cause mortality (HR=0.63 (95% CI 0.55 to 0.71) wrist; HR=0.93 (95% CI 0.87 to 0.98) hip). A significant association for the ratio of time spent in light physical activity and sedentary time was only found in hip accelerometer-based studies (HR=0.5, 95% CI 0.42 to 0.62). In studies based on hip accelerometer, the association between moderate to vigorous physical activity and mortality was modified by the balance of time spent in light physical activity and sedentary time.CONCLUSION: This federated analysis shows a joint dose-response association between the daily balance of time spent in physical activity of different intensities and sedentary behaviour with all-cause mortality, while sleep duration does not appear to be significant. The strongest association is with time spent in moderate to vigorous physical activity, but it is modified by the balance of time spent in light physical activity relative to sedentary behaviour.
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| 17. |
- Conley, R. B., et al.
(author)
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Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition
- 2020
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 35:1, s. 36-52
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Journal article (peer-reviewed)abstract
- Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk of future fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring for adverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). (c) 2019 American Society for Bone and Mineral Research.
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| 18. |
- Gyldenkerne, Christine, et al.
(author)
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Coronary Artery Lesion Lipid Content and Plaque Burden in Diabetic and Nondiabetic Patients : PROSPECT II
- 2023
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In: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 147:6, s. 469-481
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Journal article (peer-reviewed)abstract
- BACKGROUND: Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content.METHODS: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion-related MACEs and high-risk plaque characteristics.RESULTS: Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14-3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12-12.77)]) and nonculprit lesion-related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25-6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P=0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P=0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P=0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P=0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21-5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86-1.69]).CONCLUSIONS: Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging.
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| 19. |
- Jansen, Willemijn J, et al.
(author)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Journal article (peer-reviewed)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 20. |
- Jonsson, H. J. M., et al.
(author)
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Correlation strength, orbital-selective incoherence, and local moments formation in the magnetic MAX-phase Mn2GaC
- 2022
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In: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 105:3
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Journal article (peer-reviewed)abstract
- We perform a theoretical study of the electronic structure and magnetic properties of the prototypical magnetic MAX-phase Mn2GaC with the main focus given to the origin of magnetic interactions in this system. Using the density functional theory+dynamical mean-field theory (DFT+DMFT) method, we explore the effects of electron-electron interactions and magnetic correlations on the electronic properties, magnetic state, and spectral weight coherence of paramagnetic and magnetically ordered phases of Mn2GaC. We also benchmark the DFT-based disordered local moment approach for this system by comparing the obtained electronic and magnetic properties with that of the DFT+DMFT method. Our results reveal a complex magnetic behavior characterized by a near degeneracy of the ferro-and antiferromagnetic configurations of Mn2GaC, implying a high sensitivity of its magnetic state to fine details of the crystal structure and unit-cell volume, consistent with experimental observations. We observe robust local-moment behavior and orbital-selective incoherence of the spectral properties of Mn2GaC, implying the importance of orbital-dependent localization of the Mn 3d states. We find that Mn2GaC can be described in terms of local magnetic moments, which may be modeled by DFT with disordered local moments. However, the magnetic properties are dictated by the proximity to the regime of formation of local magnetic moments, in which the localization is in fact driven by Hunds exchange interaction, and not the Coulomb interaction.
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| 21. |
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| 24. |
- Maniv, A., et al.
(author)
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Microscopic evidence for Mn-induced long range magnetic ordering in MAX phase compounds
- 2021
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In: Journal of Physics. - : IOP PUBLISHING LTD. - 0953-8984 .- 1361-648X. ; 33:2
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Journal article (peer-reviewed)abstract
- Zero and low field nuclear magnetic resonance measurements have been performed on MAX phase samples (Cr1-xMnx)(2)AC withA= Ge and Ga in order to obtain local microscopic information on the nature of magnetism in this system. Our results unambiguously provide evidence for the existence of long-range magnetic order in (Cr0.96Mn0.04)(2)GeC and for (Cr0.93Mn0.07)(2)GaC, but not for (Cr0.97Mn0.03)(2)GaC. We point to a possible dependence of long range magnetic order in these MAX phase compounds on theAatom.
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| 25. |
- Nguyen, Thanh N, et al.
(author)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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In: Neurology. - 1526-632X. ; 100:4
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Journal article (peer-reviewed)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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| 26. |
- Rosén, Helena, et al.
(author)
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Persons’ experiences of having hypertension – an interview study
- 2022
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In: International Journal of Nursing Studies Advances. - : Elsevier BV. - 2666-142X. ; 4
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Journal article (peer-reviewed)abstract
- Backgroundamong the 1–1.5 billion persons with hypertension globally only, 20–30% have controlled blood pressure (BP). The most important problem identified is non-adherence to treatment, i.e., failure to change lifestyle and to take prescribed medication. Knowledge about the reasons for this is limited.ObjectivesThe aim of the study was to explore people's experiences of having hypertension.DesignInductive design based on qualitative interviews.SettingsThe south of Sweden.ParticipantsTwelve adults diagnosed with hypertension and treated in primary care were interviewed.MethodsThe transcribed interviews were analysed using content analysis, which rendered three categories.ResultsThe individuals adapted to their diagnosis in different ways. Collaboration with the staff gave security, but the persons still perceived anxiety and uncertainty.ConclusionsTo meet the needs of people with hypertension, strategies such as person-centred counselling and care, using digital interventions, following national guidelines and starting nurse-led clinics, may be of help. These strategies can give a foundation for increased self-efficacy, which is crucial for persons to be able to change lifestyle and adhere to prescribed medication in order to achieve BP control.
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| 27. |
- Sanchez-Grande, Ana, et al.
(author)
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Surface-Assisted Synthesis of N-Containing pi-Conjugated Polymers
- 2022
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In: Advanced Science. - : Wiley. - 2198-3844. ; 9:19
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Journal article (peer-reviewed)abstract
- On-surface synthesis has recently emerged as a powerful strategy to design conjugated polymers previously precluded in conventional solution chemistry. Here, an N-containing pentacene-based precursor (tetraazapentacene) is ex-professo synthesized endowed with terminal dibromomethylene (:CBr2) groups to steer homocoupling via dehalogenation on metallic supports. Combined scanning probe microscopy investigations complemented by theoretical calculations reveal how the substrate selection drives different reaction mechanisms. On Ag(111) the dissociation of bromine atoms at room temperature triggers the homocoupling of tetraazapentacene units together with the binding of silver adatoms to the nitrogen atoms of the monomers giving rise to a N-containing conjugated coordination polymer (P1). Subsequently, P1 undergoes ladderization at 200 degrees C, affording a pyrrolopyrrole-bridged conjugated polymer (P2). On Au(111) the formation of the intermediate polymer P1 is not observed and, instead, after annealing at 100 degrees C, the conjugated ladder polymer P2 is obtained, revealing the crucial role of metal adatoms on Ag(111) as compared to Au(111). Finally, on Ag(100) the loss of :CBr2 groups affords the formation of tetraazapentacene monomers, which coexist with polymer P1. Our results contribute to introduce protocols for the synthesis of N-containing conjugated polymers, illustrating the selective role of the metallic support in the underlying reaction mechanisms.
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| 28. |
- Sikkema, Lisa, et al.
(author)
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An integrated cell atlas of the lung in health and disease
- 2023
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In: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 29:6, s. 1563-1577
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Journal article (peer-reviewed)abstract
- Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1 + profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.
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| 29. |
- Stockman, Jessica, et al.
(author)
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Ankle-foot orthoses among children with cerebral palsy : a cross-sectional population-based register study of 8,928 children living in Northern Europe
- 2023
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In: BMC Musculoskeletal Disorders. - : BMC. - 1471-2474. ; 24:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Cerebral palsy (CP) is an umbrella term where an injury to the immature brain affects muscle tone and motor control, posture, and at times, the ability to walk and stand. Orthoses can be used to improve or maintain function. Ankle-foot orthoses (AFOs) are the most frequently used orthoses in children with CP. However, how commonly AFOs are used by children and adolescents with CP is still unknown. The aims of this study were to investigate and describe the use of AFOs in children with CP in Sweden, Norway, Finland, Iceland, Scotland, and Denmark, and compare AFO use between countries and by gross motor function classification system (GMFCS) level, CP subtype, sex, and age.METHOD: Aggregated data on 8,928 participants in the national follow-up programs for CP for the respective countries were used. Finland does not have a national follow-up program for individuals with CP and therefore a study cohort was used instead. Use of AFOs were presented as percentages. Logistic regression models were used to compare the use of AFOs among countries adjusted for age, CP subtype, GMFCS level, and sex.RESULTS: The proportion of AFO use was highest in Scotland (57%; CI 54-59%) and lowest in Denmark (35%; CI 33-38%). After adjusting for GMFCS level, children in Denmark, Finland, and Iceland had statistically significantly lower odds of using AFOs whereas children in Norway and Scotland reported statistically significantly higher usage than Sweden.CONCLUSION: In this study, the use of AFOs in children with CP in countries with relatively similar healthcare systems, differed between countries, age, GMFCS level, and CP subtype. This indicates a lack of consensus as to which individuals benefit from using AFOs. Our findings present an important baseline for the future research and development of practical guidelines in terms of who stands to benefit from using AFOs.
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| 30. |
- Sungnak, W., et al.
(author)
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SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes
- 2020
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In: Nature Medicine. - : Nature Research. - 1078-8956 .- 1546-170X. ; 26:5, s. 681-687
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Journal article (peer-reviewed)abstract
- We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.
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| 31. |
- Wen, J, et al.
(author)
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Rare tandem repeat expansions associate with genes involved in synaptic and neuronal signaling functions in schizophrenia
- 2023
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In: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 28:21, s. 475-482
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Journal article (peer-reviewed)abstract
- Tandem repeat expansions (TREs) are associated with over 60 monogenic disorders and have recently been implicated in complex disorders such as cancer and autism spectrum disorder. The role of TREs in schizophrenia is now emerging. In this study, we have performed a genome-wide investigation of TREs in schizophrenia. Using genome sequence data from 1154 Swedish schizophrenia cases and 934 ancestry-matched population controls, we have detected genome-wide rare (<0.1% population frequency) TREs that have motifs with a length of 2–20 base pairs. We find that the proportion of individuals carrying rare TREs is significantly higher in the schizophrenia group. There is a significantly higher burden of rare TREs in schizophrenia cases than in controls in genic regions, particularly in postsynaptic genes, in genes overlapping brain expression quantitative trait loci, and in brain-expressed genes that are differentially expressed between schizophrenia cases and controls. We demonstrate that TRE-associated genes are more constrained and primarily impact synaptic and neuronal signaling functions. These results have been replicated in an independent Canadian sample that consisted of 252 schizophrenia cases of European ancestry and 222 ancestry-matched controls. Our results support the involvement of rare TREs in schizophrenia etiology.
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