| 1. |
- Niemi, MEK, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
- Kanai, M, et al.
(author)
-
- 2023
-
swepub:Mat__t
|
|
| 3. |
- Mishra, A, et al.
(author)
-
Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
-
Journal article (peer-reviewed)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
|
|
| 4. |
- Ramdas, S., et al.
(author)
-
A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
-
In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
-
Journal article (peer-reviewed)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
|
|
| 5. |
- Hageman, S., et al.
(author)
-
SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe
- 2021
-
In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 42:25, s. 2439-2454
-
Journal article (peer-reviewed)abstract
- Aims The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40-69 years in Europe. Methods and results We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65-0.68) to 0.81 (0.76-0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low- risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries. Conclusion SCORE2-a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations-enhances the identification of individuals at higher risk of developing CVD across Europe.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Dunn, R. J. H., et al.
(author)
-
GLOBAL CLIMATE : State of the Climate in 2020
- 2021
-
In: Bulletin of the American Meteorological Society. - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 102:8
-
Journal article (peer-reviewed)
|
|
| 15. |
|
|
| 16. |
- Ades, M., et al.
(author)
-
Global Climate : in State of the climate in 2019
- 2020
-
In: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 101:8, s. S17-S127
-
Journal article (peer-reviewed)
|
|
| 17. |
- Ades, M., et al.
(author)
-
GLOBAL CLIMATE
- 2020
-
In: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007 .- 1520-0477. ; 101:8
-
Journal article (peer-reviewed)
|
|
| 18. |
|
|
| 19. |
- Carter, J. A., et al.
(author)
-
Ground-based and additional science support for SMILE
- 2024
-
In: Earth and Planetary Physics. - : Science Press. - 2096-3955. ; 8:1, s. 275-298
-
Journal article (peer-reviewed)abstract
- The joint European Space Agency and Chinese Academy of Sciences Solar wind Magnetosphere Ionosphere Link Explorer (SMILE) mission will explore global dynamics of the magnetosphere under varying solar wind and interplanetary magnetic field conditions, and simultaneously monitor the auroral response of the Northern Hemisphere ionosphere. Combining these large-scale responses with medium and fine-scale measurements at a variety of cadences by additional ground-based and space-based instruments will enable a much greater scientific impact beyond the original goals of the SMILE mission. Here, we describe current community efforts to prepare for SMILE, and the benefits and context various experiments that have explicitly expressed support for SMILE can offer. A dedicated group of international scientists representing many different experiment types and geographical locations, the Ground-based and Additional Science Working Group, is facilitating these efforts. Preparations include constructing an online SMILE Data Fusion Facility, the discussion of particular or special modes for experiments such as coherent and incoherent scatter radar, and the consideration of particular observing strategies and spacecraft conjunctions. We anticipate growing interest and community engagement with the SMILE mission, and we welcome novel ideas and insights from the solar-terrestrial community.
|
|
| 20. |
- Kanoni, Stavroula, et al.
(author)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
|
|
| 21. |
- Prigge, R., et al.
(author)
-
International comparison of glycaemic control in people with type 1 diabetes: an update and extension
- 2022
-
In: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 39:5
-
Journal article (peer-reviewed)abstract
- Aims: To update and extend a previous cross-sectional international comparison of glycaemic control in people with type 1 diabetes. Methods: Data were obtained for 520,392 children and adults with type 1 diabetes from 17 population and five clinic-based data sources in countries or regions between 2016 and 2020. Median HbA1c(IQR) and proportions of individuals with HbA1c < 58mmol/mol (<7.5%), 58–74mmol/mol (7.5–8.9%) and ≥75mmol/mol (≥9.0%) were compared between populations for individuals aged <15, 15–24 and ≥25 years. Logistic regression was used to estimate the odds ratio (OR) of HbA1c < 58mmol/mol (<7.5%) relative to ≥58mmol/mol (≥7.5%), stratified and adjusted for sex, age and data source. Where possible, changes in the proportion of individuals in each HbA1c category compared to previous estimates were calculated. Results: Median HbA1c varied from 55 to 79mmol/mol (7.2 to 9.4%) across data sources and age groups so a pooled estimate was deemed inappropriate. OR (95% CI) for HbA1c< 58mmol/mol (<7.5%) were 0.91 (0.90–0.92) for women compared to men, 1.68 (1.65–1.71) for people aged <15years and 0.81 (0.79–0.82) aged15–24years compared to those aged ≥25years. Differences between populations persisted after adjusting for sex, age and data source. In general, compared to our previous analysis, the proportion of people with an HbA1c<58mmol/l (<7.5%) increased and proportions of people with HbA1c≥ 75mmol/mol (≥9.0%) decreased. Conclusions: Glycaemic control of type 1 diabetes continues to vary substantially between age groups and data sources. While some improvement over time has been observed, glycaemic control remains sub-optimal for most people with Type 1 diabetes.
|
|
| 22. |
|
|
| 23. |
- Tsiligiannis, Epameinondas, et al.
(author)
-
A Four Carbon Organonitrate as a Significant Product of Secondary Isoprene Chemistry
- 2022
-
In: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 49:11
-
Journal article (peer-reviewed)abstract
- Oxidation of isoprene by nitrate radicals (NO3) or by hydroxyl radicals (OH) under high NOx conditions forms a substantial amount of organonitrates (ONs). ONs impact NOx concentrations and consequently ozone formation while also contributing to secondary organic aerosol. Here we show that the ONs with the chemical formula C4H7NO5 are a significant fraction of isoprene-derived ONs, based on chamber experiments and ambient measurements from different sites around the globe. From chamber experiments we found that C4H7NO5 isomers contribute 5%-17% of all measured ONs formed during nighttime and constitute more than 40% of the measured ONs after further daytime oxidation. In ambient measurements C4H7NO5 isomers usually dominate both nighttime and daytime, implying a long residence time compared to C-5 ONs which are removed more rapidly. We propose potential nighttime sources and secondary formation pathways, and test them using a box model with an updated isoprene oxidation scheme.
|
|
| 24. |
- Dotto, T. S., et al.
(author)
-
Ocean variability beneath Thwaites Eastern Ice Shelf driven by the Pine Island Bay Gyre strength
- 2022
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
-
Journal article (peer-reviewed)abstract
- West Antarctic ice-shelf thinning is primarily caused by ocean-driven basal melting. Here we assess ocean variability below Thwaites Eastern Ice Shelf (TEIS) and reveal the importance of local ocean circulation and sea-ice. Measurements obtained from two sub-ice-shelf moorings, spanning January 2020 to March 2021, show warming of the ice-shelf cavity and an increase in meltwater fraction of the upper sub-ice layer. Combined with ocean modelling results, our observations suggest that meltwater from Pine Island Ice Shelf feeds into the TEIS cavity, adding to horizontal heat transport there. We propose that a weakening of the Pine Island Bay gyre caused by prolonged sea-ice cover from April 2020 to March 2021 allowed meltwater-enriched waters to enter the TEIS cavity, which increased the temperature of the upper layer. Our study highlights the sensitivity of ocean circulation beneath ice shelves to local atmosphere-sea-ice-ocean forcing in neighbouring open oceans.
|
|
| 25. |
- Heston, M. B., et al.
(author)
-
Gut inflammation associated with age and Alzheimer's disease pathology: a human cohort study
- 2023
-
In: Scientific Reports. - 2045-2322. ; 13:1
-
Journal article (peer-reviewed)abstract
- Age-related disease may be mediated by low levels of chronic inflammation ("inflammaging"). Recent work suggests that gut microbes can contribute to inflammation via degradation of the intestinal barrier. While aging and age-related diseases including Alzheimer's disease (AD) are linked to altered microbiome composition and higher levels of gut microbial components in systemic circulation, the role of intestinal inflammation remains unclear. To investigate whether greater gut inflammation is associated with advanced age and AD pathology, we assessed fecal samples from older adults to measure calprotectin, an established marker of intestinal inflammation which is elevated in diseases of gut barrier integrity. Multiple regression with maximum likelihood estimation and Satorra-Bentler corrections were used to test relationships between fecal calprotectin and clinical diagnosis, participant age, cerebrospinal fluid biomarkers of AD pathology, amyloid burden measured using 11C-Pittsburgh compound B positron emission tomography (PiB PET) imaging, and performance on cognitive tests measuring executive function and verbal learning and recall. Calprotectin levels were elevated in advanced age and were higher in participants diagnosed with amyloid-confirmed AD dementia. Additionally, among individuals with AD dementia, higher calprotectin was associated with greater amyloid burden as measured with PiB PET. Exploratory analyses indicated that calprotectin levels were also associated with cerebrospinal fluid markers of AD, and with lower verbal memory function even among cognitively unimpaired participants. Taken together, these findings suggest that intestinal inflammation is linked with brain pathology even in the earliest disease stages. Moreover, intestinal inflammation may exacerbate the progression toward AD.
|
|
| 26. |
- Keuper, Frida, et al.
(author)
-
Carbon loss from northern circumpolar permafrost soils amplified by rhizosphere priming
- 2020
-
In: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 13, s. 560-565
-
Journal article (peer-reviewed)abstract
- As global temperatures continue to rise, a key uncertainty of climate projections is the microbial decomposition of vast organic carbon stocks in thawing permafrost soils. Decomposition rates can accelerate up to fourfold in the presence of plant roots, and this mechanism-termed the rhizosphere priming effect-may be especially relevant to thawing permafrost soils as rising temperatures also stimulate plant productivity in the Arctic. However, priming is currently not explicitly included in any model projections of future carbon losses from the permafrost area. Here, we combine high-resolution spatial and depth-resolved datasets of key plant and permafrost properties with empirical relationships of priming effects from living plants on microbial respiration. We show that rhizosphere priming amplifies overall soil respiration in permafrost-affected ecosystems by similar to 12%, which translates to a priming-induced absolute loss of similar to 40 Pg soil carbon from the northern permafrost area by 2100. Our findings highlight the need to include fine-scale ecological interactions in order to accurately predict large-scale greenhouse gas emissions, and suggest even tighter restrictions on the estimated 200 Pg anthropogenic carbon emission budget to keep global warming below 1.5 degrees C.
|
|
| 27. |
- Lembrechts, Jonas J., et al.
(author)
-
SoilTemp : A global database of near-surface temperature
- 2020
-
In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 26:11, s. 6616-6629
-
Journal article (peer-reviewed)abstract
- Current analyses and predictions of spatially explicit patterns and processes in ecology most often rely on climate data interpolated from standardized weather stations. This interpolated climate data represents long-term average thermal conditions at coarse spatial resolutions only. Hence, many climate-forcing factors that operate at fine spatiotemporal resolutions are overlooked. This is particularly important in relation to effects of observation height (e.g. vegetation, snow and soil characteristics) and in habitats varying in their exposure to radiation, moisture and wind (e.g. topography, radiative forcing or cold-air pooling). Since organisms living close to the ground relate more strongly to these microclimatic conditions than to free-air temperatures, microclimatic ground and near-surface data are needed to provide realistic forecasts of the fate of such organisms under anthropogenic climate change, as well as of the functioning of the ecosystems they live in. To fill this critical gap, we highlight a call for temperature time series submissions to SoilTemp, a geospatial database initiative compiling soil and near-surface temperature data from all over the world. Currently, this database contains time series from 7,538 temperature sensors from 51 countries across all key biomes. The database will pave the way toward an improved global understanding of microclimate and bridge the gap between the available climate data and the climate at fine spatiotemporal resolutions relevant to most organisms and ecosystem processes.
|
|
| 28. |
- Schmitz, M., et al.
(author)
-
Demonstration of an aggregated biomarker response approach to assess the impact of point and diffuse contaminant sources in feral fish in a small river case study
- 2022
-
In: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 804
-
Journal article (peer-reviewed)abstract
- The assessment of the exposure of aquatic wildlife to complex environmental mixtures of chemicals originating from both point and diffuse sources and evaluating the potential impact thereof constitutes a significant step towards mitigating toxic pressure and the improvement of ecological status. In the current proof-of-concept study, we demonstrate the potential of a novel Aggregated Biomarker Response (ABR) approach involving a comprehensive set of biomarkers to identify complex exposure and impacts on wild brown trout (Salmo trutta fario). Our scenario used a small lowland river in Germany (Holtemme river in the Elbe river catchment) impacted by two wastewater treatment plants (WWTP) and diffuse agricultural runoff as a case study. The trout were col-lected along a pollution gradient (characterised in a parallel study) in the river. Compared to fish from the refer-ence site upstream of the first WWTP, the trout collected downstream of the WWTPs showed a significant increase in micronucleus formation, phase I and II enzyme activities, and oxidative stress parameters in agree-ment with increasing exposure to various chemicals. By integrating single biomarker responses into an aggre-gated biomarker response, the two WWTPs' contribution to the observed toxicity could be clearly differentiated. The ABR results were supported by chemical analyses and whole transcriptome data, which re-vealed alterations of steroid biosynthesis and associated pathways, including an anti-androgenic effect, as some of the key drivers of the observed toxicity. Overall, this combined approach of in situ biomarker responses complemented with molecular pathway analysis allowed for a comprehensive ecotoxicological assessment of fish along the river. This study provides evidence for specific hazard potentials caused by mixtures of agricultural and WWTP derived chemicals at sublethal concentrations. Using aggregated biomarker responses combined with chemical analyses enabled an evidence-based ranking of sites with different degrees of pollution according to toxic stress and observed effects. (c) 2021 Elsevier B.V. All rights reserved.
|
|
| 29. |
- Blume-Werry, Gesche, 1985-, et al.
(author)
-
Arctic rooting depth distribution influences modelled carbon emissions but cannot be inferred from aboveground vegetation type
- 2023
-
In: New Phytologist. - : John Wiley & Sons. - 0028-646X .- 1469-8137. ; 240:2, s. 502-514
-
Journal article (peer-reviewed)abstract
- The distribution of roots throughout the soil drives depth-dependent plant–soil interactions and ecosystem processes, particularly in arctic tundra where plant biomass, is predominantly belowground. Vegetation is usually classified from aboveground, but it is unclear whether such classifications are suitable to estimate belowground attributes and their consequences, such as rooting depth distribution and its influence on carbon cycling. We performed a meta-analysis of 55 published arctic rooting depth profiles, testing for differences both between distributions based on aboveground vegetation types (Graminoid, Wetland, Erect-shrub, and Prostrate-shrub tundra) and between ‘Root Profile Types’ for which we defined three representative and contrasting clusters. We further analyzed potential impacts of these different rooting depth distributions on rhizosphere priming-induced carbon losses from tundra soils. Rooting depth distribution hardly differed between aboveground vegetation types but varied between Root Profile Types. Accordingly, modelled priming-induced carbon emissions were similar between aboveground vegetation types when they were applied to the entire tundra, but ranged from 7.2 to 17.6 Pg C cumulative emissions until 2100 between individual Root Profile Types. Variations in rooting depth distribution are important for the circumpolar tundra carbon-climate feedback but can currently not be inferred adequately from aboveground vegetation type classifications.
|
|
| 30. |
- Dong, R. C., et al.
(author)
-
Principal components from untargeted cerebrospinal fluid metabolomics associated with Alzheimer's disease biomarkers
- 2022
-
In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 117, s. 12-23
-
Journal article (peer-reviewed)abstract
- Studying the correlation between cerebrospinal fluid (CSF) metabolites and the Alzheimer's Disease (AD) biomarkers may offer a window to the alterations of the brain metabolome and unveil potential biological mechanisms underlying AD. In this analysis, 308 CSF metabolites from 338 individuals of Wisconsin Registry for Alzheimer's Prevention and Wisconsin Alzheimer's Disease Research Center were included in a principal component analysis (PCA). The resulted principal components (PCs) were tested for association with CSF total tau (t-tau), phosphorylated tau (p-tau), amyloid beta 42 (A beta 42), and A beta 42/40 ratio using linear regression models. Significant PCs were further tested with other CSF NeuroToolKit (NTK) and imaging biomarkers. Using a Bonferroni corrected p < 0.05, 5 PCs were significantly associated with CSF p-tau and t-tau and 3 PCs were significantly associated with CSF A beta 42. Pathway analysis suggested that these PCS were enriched in 6 pathways, including metabolism of caffeine and nicotinate and nicotinamide. This study provides evidence that CSF metabolites are associated with AD pathology through core AD biomarkers and other NTK markers and suggests potential pathways to follow up in future studies.(c) 2022 Elsevier Inc. All rights reserved.
|
|
| 31. |
- Ehlers, Anke, et al.
(author)
-
A randomised controlled trial of therapist-assisted online psychological therapies for posttraumatic stress disorder (STOP-PTSD) : trial protocol
- 2020
-
In: Trials. - : BioMed Central. - 1745-6215. ; 21:1
-
Journal article (peer-reviewed)abstract
- Background Over the last few decades, effective psychological treatments for posttraumatic stress disorder (PTSD) have been developed, but many patients are currently unable to access these treatments. There is initial evidence that therapist-assisted internet-based psychological treatments are effective for PTSD and may help increase access, but it remains unclear which of these treatments work best and are most acceptable to patients. This randomised controlled trial will compare a trauma-focussed and a nontrauma-focussed therapist-assisted cognitive behavioural Internet treatment for PTSD: Internet-delivered cognitive therapy for PTSD (iCT-PTSD) and internet-delivered stress management therapy (iStress-PTSD). Methods/design The study is a single-blind, randomised controlled trial comparing iCT-PTSD, iStress-PTSD and a 13-week wait-list condition, with an embedded process study. Assessors of treatment outcome will be blinded to trial arm. Two hundred and seventeen participants who meet DSM-5 criteria for PTSD will be randomly allocated by a computer programme to iCT-PTSD, iStress-PTSD or wait-list at a 3:3:1 ratio. The primary assessment point is at 13 weeks, and further assessments are taken at 6, 26, 39 and 65 weeks. The primary outcome measure is the severity of PTSD symptoms as measured by the PTSD Checklist for DSM-5 (PCL-5). Secondary measures of PTSD symptoms are the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) and the Impact of Event Scale-Revised (IES-R). Other symptoms and well-being will be assessed with the Patient Health Questionnaire (PHQ-9), Generalised Anxiety Disorder Scale (GAD-7), WHO (Five) Well-Being Index, Work and Social Adjustment Scale (WSAS), Endicott Quality of Life Scale (QoL), and Insomnia Sleep Index (ISI). Health economics analyses will consider quality of life, productivity, health resource utilisation, employment status and state benefits, and treatment delivery costs. Process analyses will investigate candidate mediators and moderators of outcome. Patient experience will be assessed by interview and questionnaire. Discussion This study will be the first to compare the efficacy of a trauma-focussed and nontrauma-focussed therapist-assisted online cognitive behavioural treatment for people with posttraumatic stress disorder.
|
|
| 32. |
- Ehlers, Anke, et al.
(author)
-
Therapist-assisted online psychological therapies differing in trauma focus for post-traumatic stress disorder (STOP-PTSD) : a UK-based, single-blind, randomised controlled trial
- 2023
-
In: The lancet. Psychiatry. - : ELSEVIER SCI LTD. - 2215-0374 .- 2215-0366. ; 10:8, s. 608-622
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Many patients are currently unable to access psychological treatments for post-traumatic stress disorder (PTSD), and it is unclear which types of therapist-assisted internet-based treatments work best. We aimed to investigate whether a novel internet-delivered cognitive therapy for PTSD (iCT-PTSD), which implements all procedures of a first-line, trauma-focused intervention recommended by the UK National Institute for Health and Care Excellence (NICE) for PTSD, is superior to internet-delivered stress management therapy for PTSD (iStress-PTSD), a comprehensive cognitive behavioural treatment programme focusing on a wide range of coping skills.METHODS: We did a single-blind, randomised controlled trial in three locations in the UK. Participants (≥18 years) were recruited from UK National Health Service (NHS) Improving Access to Psychological Therapies (IAPT) services or by self-referral and met DSM-5 criteria for PTSD to single or multiple events. Participants were randomly allocated by a computer programme (3:3:1) to iCT-PTSD, iStress-PTSD, or a 3-month waiting list with usual NHS care, after which patients who still met PTSD criteria were randomly allocated (1:1) to iCT-PTSD or iStress-PTSD. Randomisation was stratified by location, duration of PTSD (<18 months or ≥18 months), and severity of PTSD symptoms (high vs low). iCT-PTSD and iStress-PTSD were delivered online with therapist support by messages and short weekly phone calls over the first 12 weeks (weekly treatment phase), and three phone calls over the next 3 months (booster phase). The primary outcome was the severity of PTSD symptoms at 13 weeks after random assignment, measured by self-report on the PTSD Checklist for DSM-5 (PCL-5), and analysed by intention-to-treat. Safety was assessed in all participants who started treatment. Process analyses investigated acceptability and compliance with treatment, and candidate moderators and mediators of outcome. The trial was prospectively registered with the ISRCTN registry, ISRCTN16806208.FINDINGS: Of the 217 participants, 158 (73%) self-reported as female, 57 (26%) as male, and two (1%) as other; 170 (78%) were White British, 20 (9%) were other White, six (3%) were Asian, ten (5%) were Black, eight (4%) had a mixed ethnic background, and three (1%) had other ethnic backgrounds. Mean age was 36·36 years (SD 12·11; range 18-71 years). 52 (24%) participants met self-reported criteria for ICD-11 complex PTSD. Fewer than 10% of participants dropped out of each treatment group. iCT-PTSD was superior to iStress-PTSD in reducing PTSD symptoms, showing an adjusted difference on the PCL-5 of -4·92 (95% CI -8·92 to -0·92; p=0·016; standardised effect size d=0·38 [0·07 to 0·69]) for immediate allocations and -5·82 (-9·59 to -2·04; p=0·0027; d=0·44 [0·15 to 0·72]) for all treatment allocations. Both treatments were superior to the waiting list for PCL-5 at 13 weeks (d=1·67 [1·23 to 2·10] for iCT-PTSD and 1·29 [0·85 to 1·72] for iStress-PTSD). The advantages in outcome for iCT-PTSD were greater for participants with high dissociation or complex PTSD symptoms, and mediation analyses showed both treatments worked by changing negative meanings of the trauma, unhelpful coping, and flashback memories. No serious adverse events were reported.INTERPRETATION: Trauma-focused iCT-PTSD is effective and acceptable to patients with PTSD, and superior to a non-trauma-focused cognitive behavioural stress management therapy, suggesting that iCT-PTSD is an effective way of delivering the contents of CT-PTSD, one of the NICE-recommended first-line treatments for PTSD, while reducing therapist time compared with face-to-face therapy.FUNDING: Wellcome Trust, UK National Institute for Health and Care Research Oxford Health Biomedical Research Centre.
|
|
| 33. |
- Holzhauser, S, et al.
(author)
-
Targeted Therapy With PI3K and FGFR Inhibitors on Human Papillomavirus Positive and Negative Tonsillar and Base of Tongue Cancer Lines With and Without Corresponding Mutations
- 2021
-
In: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 11, s. 640490-
-
Journal article (peer-reviewed)abstract
- Human papillomavirus positive (HPV+) tonsillar and base of tongue squamous cell carcinoma (TSCC/BOTSCC), the major subsites of oropharyngeal squamous cell carcinoma (OPSCC) have favorable outcome, but upon relapse, outcome is poor and new therapies needed. Since, phosphatidyl-inositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) and fibroblast-growth-factor-receptor-3 (FGFR3) mutations often occur in such tumors, here, we tested targeted therapy directed to such genes in TSCC/BOTSCC cell lines. We also combined the two types of inhibitors with each other, and cisplatin or docetaxel that are used clinically.MethodsThe HPV+ CU-OP-2, -3, -20, UPCI-SCC-154, and HPV- CU-OP-17 and UT-SCC-60A cell lines were first tested for common PIK3CA/FGFR3 mutations by competitive-allele-specific TaqMan-PCR. They were then treated with the food and drug administration (FDA) approved drugs, alpelisib (BYL719) and erdafitinib (JNJ-42756493) alone and in combination with cisplatin or docetaxel. Viability, proliferation, apoptosis and cytotoxicity responses were thereafter followed by WST-1 assays and the IncuCyte S3 Live® Cell Analysis System.ResultsHPV+ CU-OP-2 had a pS249C-FGFR3, and like CU-OP-20, a pE545K-PIK3CA mutation, while no other lines had such mutations. Irrespectively, dose dependent responses to all PI3K/FGFR inhibitors were obtained, and upon combining the inhibitors, positive effects were observed. Cisplatin and docetaxel also induced dose dependent responses, and upon combination with the inhibitors, both positive and neutral effects were found.ConclusionsThe data suggest that FDA approved drugs alpelisib and erdafitinib efficiently inhibit TSCC/BOTSCC cell line growth, especially when combined irrespective of presence of corresponding mutations and should be further explored, for use upon recurrent disease.
|
|
| 34. |
- Kirdyanov, Alexander V., et al.
(author)
-
Ecological and conceptual consequences of Arctic pollution
- 2020
-
In: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 23:12, s. 1827-1837
-
Journal article (peer-reviewed)abstract
- Although the effect of pollution on forest health and decline received much attention in the 1980s, it has not been considered to explain the 'Divergence Problem' in dendroclimatology; a decoupling of tree growth from rising air temperatures since the 1970s. Here we use physical and biogeochemical measurements of hundreds of living and dead conifers to reconstruct the impact of heavy industrialisation around Norilsk in northern Siberia. Moreover, we develop a forward model with surface irradiance forcing to quantify long-distance effects of anthropogenic emissions on the functioning and productivity of Siberia's taiga. Downwind from the world's most polluted Arctic region, tree mortality rates of up to 100% have destroyed 24,000 km(2)boreal forest since the 1960s, coincident with dramatic increases in atmospheric sulphur, copper, and nickel concentrations. In addition to regional ecosystem devastation, we demonstrate how 'Arctic Dimming' can explain the circumpolar 'Divergence Problem', and discuss implications on the terrestrial carbon cycle.
|
|
| 35. |
- Lagou, Vasiliki, et al.
(author)
-
Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
-
In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
|
|
| 36. |
- McGurnaghan, S. J., et al.
(author)
-
Development and validation of a cardiovascular risk prediction model in type 1 diabetes
- 2021
-
In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 64, s. 2001-2011
-
Journal article (peer-reviewed)abstract
- Aims/hypothesis We aimed to report current rates of CVD in type 1 diabetes and to develop a CVD risk prediction tool for type 1 diabetes. Methods A cohort of 27,527 people with type 1 diabetes without prior CVD was derived from the national register in Scotland. Incident CVD events during 199,552 person-years of follow-up were ascertained using hospital admissions and death registers. A Poisson regression model of CVD was developed and then validated in the Swedish National Diabetes Register (n = 33,183). We compared the percentage with a high 10 year CVD risk (i.e., >= 10%) using the model with the percentage eligible for statins using current guidelines by age. Results The age-standardised rate of CVD per 100,000 person-years was 4070 and 3429 in men and women, respectively, with type 1 diabetes in Scotland, and 4014 and 3956 in men and women in Sweden. The final model was well calibrated (Hosmer- Lemeshow test p > 0.05) and included a further 22 terms over a base model of age, sex and diabetes duration (C statistic 0.82; 95% CI 0.81, 0.83). The model increased the base model C statistic foam 0.66 to 0.80, from 0.60 to 0.75 and from 0.62 to 0.68 in those aged <40, 40-59 and >= 60 years, respectively (alp values <0.005). The model required minimal calibration in Sweden and had a C statistic of 0.85. Under current guidelines, >90% of those aged 20-39 years and 100% of those >= 40 years with type 1 diabetes were eligible for statins, but it was not until age 65 upwards that 100% had a modelled risk of CVD >= 10% in 10 years. Conclusions/interpretation A prediction tool such as that developed here can provide individualised risk predictions. This 10 year CVD risk prediction tool could facilitate patient discussions regarding appropriate statin prescribing. Apart from 10 year risk, such discussions may also consider longer-term CVD risk, the potential for greater benefits from early vs later statin intervention. the potential impact on quality of life of an early CVD event and evidence on safety, all of which could influence treatment decisions, particularly in younger people with type 1 diabetes.
|
|
| 37. |
- Sánchez-Cano, Beatriz, et al.
(author)
-
Mars’ plasma system. Scientific potential of coordinated multipoint missions : "The next generation"
- 2022
-
In: Experimental astronomy. - : Springer. - 0922-6435 .- 1572-9508. ; 54, s. 641-676
-
Journal article (peer-reviewed)abstract
- The objective of this White Paper, submitted to ESA’s Voyage 2050 call, is to get a more holistic knowledge of the dynamics of the Martian plasma system, from its surface up to the undisturbed solar wind outside of the induced magnetosphere. This can only be achieved with coordinated multi-point observations with high temporal resolution as they have the scientific potential to track the whole dynamics of the system (from small to large scales), and they constitute the next generation of the exploration of Mars analogous to what happened at Earth a few decades ago. This White Paper discusses the key science questions that are still open at Mars and how they could be addressed with coordinated multipoint missions. The main science questions are: (i) How does solar wind driving impact the dynamics of the magnetosphere and ionosphere? (ii) What is the structure and nature of the tail of Mars’ magnetosphere at all scales? (iii) How does the lower atmosphere couple to the upper atmosphere? (iv) Why should we have a permanent in-situ Space Weather monitor at Mars? Each science question is devoted to a specific plasma region, and includes several specific scientific objectives to study in the coming decades. In addition, two mission concepts are also proposed based on coordinated multi-point science from a constellation of orbiting and ground-based platforms, which focus on understanding and solving the current science gaps.
|
|
| 38. |
- Scahill, R. I., et al.
(author)
-
Biological and clinical characteristics of gene carriers far from predicted onset in the Huntington?s disease Young Adult Study (HD-YAS): a cross-sectional analysis
- 2020
-
In: Lancet Neurology. - : Elsevier BV. - 1474-4422. ; 19:6, s. 502-512
-
Journal article (peer-reviewed)abstract
- Background Disease-modifying treatments are in development for Huntington's disease; crucial to their success is to identify a timepoint in a patient's life when there is a measurable biomarker of early neurodegeneration while clinical function is still intact. We aimed to identify this timepoint in a novel cohort of young adult premanifest Huntington's disease gene carriers (preHD) far from predicted clinical symptom onset. Methods We did the Huntington's disease Young Adult Study (HD-YAS) in the UK. We recruited young adults with preHD and controls matched for age, education, and sex to ensure each group had at least 60 participants with imaging data, accounting for scan fails. Controls either had a family history of Huntington's disease but a negative genetic test, or no known family history of Huntington's disease. All participants underwent detailed neuropsychiatric and cognitive assessments, including tests from the Cambridge Neuropsychological Test Automated Battery and a battery assessing emotion, motivation, impulsivity and social cognition (EMOTICOM). Imaging (done for all participants without contraindications) included volumetric MRI, diffusion imaging, and multiparametric mapping. Biofluid markers of neuronal health were examined using blood and CSF collection. We did a cross-sectional analysis using general least-squares linear models to assess group differences and associations with age and CAG length, relating to predicted years to clinical onset. Results were corrected for multiple comparisons using the false discovery rate (FDR), with FDR <0.05 deemed a significant result. Findings Data were obtained between Aug 2, 2017, and April 25, 2019. We recruited 64 young adults with preHD and 67 controls. Mean ages of participants were 29.0 years (SD 5.6) and 29.1 years (5.7) in the preHD and control groups, respectively. We noted no significant evidence of cognitive or psychiatric impairment in preHD participants 23.6 years (SD 5.8) from predicted onset (FDR 0.22-0.87 for cognitive measures, 0.31-0.91 for neuropsychiatric measures). The preHD cohort had slightly smaller putamen volumes (FDR=0.03), but this did not appear to be closely related to predicted years to onset (FDR=0.54). There were no group differences in other brain imaging measures (FDR >0.16). CSF neurofilament light protein (NfL), plasma NfL, and CSF YKL-40 were elevated in this far-from-onset preHD cohort compared with controls (FDR<0.0001, =0.01, and =0.03, respectively). CSF NfL elevations were more likely in individuals closer to expected clinical onset (FDR <0.0001). Interpretation We report normal brain function yet a rise in sensitive measures of neurodegeneration in a preHD cohort approximately 24 years from predicted clinical onset. CSF NfL appears to be a more sensitive measure than plasma NfL to monitor disease progression. This preHD cohort is one of the earliest yet studied, and our findings could be used to inform decisions about when to initiate a potential future intervention to delay or prevent further neurodegeneration while function is intact.
|
|
| 39. |
-
The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
- 2022
-
In: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
-
Journal article (peer-reviewed)abstract
- This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
|
|
