| 1. |
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| 2. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 3. |
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| 4. |
- Hudson, Lawrence N., et al.
(författare)
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The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
- 2014
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
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Tidskriftsartikel (refereegranskat)abstract
- Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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| 5. |
- Vergallo, A., et al.
(författare)
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Association of plasma YKL-40 with brain amyloid-β levels, memory performance, and sex in subjective memory complainers
- 2020
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 96, s. 22-32
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Tidskriftsartikel (refereegranskat)abstract
- Neuroinflammation, a key early pathomechanistic alteration of Alzheimer's disease, may represent either a detrimental or a compensatory mechanism or both (according to the disease stage). YKL-40, a glycoprotein highly expressed in differentiated glial cells, is a candidate biomarker for in vivo tracking neuroinflammation in humans. We performed a longitudinal study in a monocentric cohort of cognitively healthy individuals at risk for Alzheimer's disease exploring whether age, sex, and the apolipoprotein E ε4 allele affect plasma YKL-40 concentrations. We investigated whether YKL-40 is associated with brain amyloid-β (Aβ) deposition, neuronal activity, and neurodegeneration as assessed via neuroimaging biomarkers. Finally, we investigated whether YKL-40 may predict cognitive performance. We found an age-associated increase of YKL-40 and observed that men display higher concentrations than women, indicating a potential sexual dimorphism. Moreover, YKL-40 was positively associated with memory performance and negatively associated with brain Aβ deposition (but not with metabolic signal). Consistent with translational studies, our results suggest a potentially protective effect of glia on incipient brain Aβ accumulation and neuronal homeostasis. © 2020 Elsevier Inc.
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| 6. |
- Vergallo, A., et al.
(författare)
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Plasma amyloid beta 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease
- 2019
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:6, s. 764-775
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Blood-based biomarkers of pathophysiological brain amyloid beta (A beta) accumulation, particularly for preclinical target and large-scale interventions, are warranted to effectively enrich Alzheimer's disease clinical trials and management. Methods: We investigated whether plasma concentrations of the A beta(1-40)/A beta(1-42) ratio, assessed using the single-molecule array (Simoa) immunoassay, may predict brain A beta positron emission tomography status in a large-scale longitudinal monocentric cohort (N = 276) of older individuals with subjective memory complaints. We performed a hypothesis-driven investigation followed by a no-apriori hypothesis study using machine learning. Results: The receiver operating characteristic curve and machine learning showed a balanced accuracy of 76.5% and 81%, respectively, for the plasma A beta(1-40)/A beta(1-42) ratio. The accuracy is not affected by the apolipoprotein E (APOE) epsilon 4 allele, sex, or age. Discussion: Our results encourage an independent validation cohort study to confirm the indication that the plasma A beta(1-40)/A beta(1-42) ratio, assessed via Simoa, may improve future standard of care and clinical trial design. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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| 7. |
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| 8. |
- Woodcock, B. A., et al.
(författare)
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Meta-analysis reveals that pollinator functional diversity and abundance enhance crop pollination and yield
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- How insects promote crop pollination remains poorly understood in terms of the contribution of functional trait differences between species. We used meta-analyses to test for correlations between community abundance, species richness and functional trait metrics with oilseed rape yield, a globally important crop. While overall abundance is consistently important in predicting yield, functional divergence between species traits also showed a positive correlation. This result supports the complementarity hypothesis that pollination function is maintained by non-overlapping trait distributions. In artificially constructed communities (mesocosms), species richness is positively correlated with yield, although this effect is not seen under field conditions. As traits of the dominant species do not predict yield above that attributed to the effect of abundance alone, we find no evidence in support of the mass ratio hypothesis. Management practices increasing not just pollinator abundance, but also functional divergence, could benefit oilseed rape agriculture.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Alejandre, Elizabeth M., et al.
(författare)
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Characterization Factors to Assess Land Use Impacts on Pollinator Abundance in Life Cycle Assessment
- 2023
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 57:8, s. 3445-3454
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Tidskriftsartikel (refereegranskat)abstract
- While wild pollinators play a key role in global food production, their assessment is currently missing from the most commonly used environmental impact assessment method, Life Cycle Assessment (LCA). This is mainly due to constraints in data availability and compatibility with LCA inventories. To target this gap, relative pollinator abundance estimates were obtained with the use of a Delphi assessment, during which 25 experts, covering 16 nationalities and 45 countries of expertise, provided scores for low, typical, and high expected abundance associated with 24 land use categories. Based on these estimates, this study presents a set of globally generic characterization factors (CFs) that allows translating land use into relative impacts to wild pollinator abundance. The associated uncertainty of the CFs is presented along with an illustrative case to demonstrate the applicability in LCA studies. The CFs based on estimates that reached consensus during the Delphi assessment are recommended as readily applicable and allow key differences among land use types to be distinguished. The resulting CFs are proposed as the first step for incorporating pollinator impacts in LCA studies, exemplifying the use of expert elicitation methods as a useful tool to fill data gaps that constrain the characterization of key environmental impacts.
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| 14. |
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| 15. |
- Hutchinson, Louise A., et al.
(författare)
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Using ecological and field survey data to establish a national list of the wild bee pollinators of crops
- 2021
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Ingår i: Agriculture, Ecosystems and Environment. - : Elsevier BV. - 0167-8809 .- 1873-2305. ; 315
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Tidskriftsartikel (refereegranskat)abstract
- The importance of wild bees for crop pollination is well established, but less is known about which species contribute to service delivery to inform agricultural management, monitoring and conservation. Using sites in Great Britain as a case study, we use a novel qualitative approach combining ecological information and field survey data to establish a national list of crop pollinating bees for four economically important crops (apple, field bean, oilseed rape and strawberry). A traits data base was used to establish potential pollinators, and combined with field data to identify both dominant crop flower visiting bee species and other species that could be important crop pollinators, but which are not presently sampled in large numbers on crops flowers. Whilst we found evidence that a small number of common, generalist species make a disproportionate contribution to flower visits, many more species were identified as potential pollinators, including rare and specialist species. Furthermore, we found evidence of substantial variation in the bee communities of different crops. Establishing a national list of crop pollinators is important for practitioners and policy makers, allowing targeted management approaches for improved ecosystem services, conservation and species monitoring. Data can be used to make recommendations about how pollinator diversity could be promoted in agricultural landscapes. Our results suggest agri-environment schemes need to support a higher diversity of species than at present, notably of solitary bees. Management would also benefit from targeting specific species to enhance crop pollination services to particular crops. Whilst our study is focused upon Great Britain, our methodology can easily be applied to other countries, crops and groups of pollinating insects.
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| 16. |
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| 17. |
- Brooks, BR, et al.
(författare)
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CHARMM: the biomolecular simulation program
- 2009
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Ingår i: Journal of computational chemistry. - : Wiley. - 1096-987X .- 0192-8651. ; 30:10, s. 1545-1614
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Tidskriftsartikel (refereegranskat)
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| 18. |
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| 19. |
- Figiel, Sandy, et al.
(författare)
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Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures
- 2023
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Ingår i: Molecular Cancer. - : Springer Nature. - 1476-4598. ; 22:1, s. 162-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx®, Decipher®, Prostadiag®) using a step-wise approach with increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.
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| 20. |
- Vandewalle, Marie, et al.
(författare)
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Functional traits as indicators of biodiversity response to land use changes across ecosystems and organisms
- 2010
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Ingår i: Biodiversity and Conservation. - : Springer Science and Business Media LLC. - 0960-3115 .- 1572-9710. ; 19:10, s. 2921-2947
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Tidskriftsartikel (refereegranskat)abstract
- Rigorous and widely applicable indicators of biodiversity are needed to monitor the responses of ecosystems to global change and design effective conservation schemes. Among the potential indicators of biodiversity, those based on the functional traits of species and communities are interesting because they can be generalized to similar habitats and can be assessed by relatively rapid field assessment across eco-regions. Functional traits, however, have as yet been rarely considered in current common monitoring schemes. Moreover, standardized procedures of trait measurement and analyses have almost exclusively been developed for plants but different approaches have been used for different groups of organisms. Here we review approaches using functional traits as biodiversity indicators focussing not on plants as usual but particularly on animal groups that are commonly considered in different biodiversity monitoring schemes (benthic invertebrates, collembolans, above ground insects and birds). Further, we introduce a new framework based on functional traits indices and illustrate it using case studies where the traits of these organisms can help monitoring the response of biodiversity to different land use change drivers. We propose and test standard procedures to integrate different components of functional traits into biodiversity monitoring schemes across trophic levels and disciplines. We suggest that the development of indicators using functional traits could complement, rather than replace, the existent biodiversity monitoring. In this way, the comparison of the effect of land use changes on biodiversity is facilitated and is expected to positively influence conservation management practices.
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| 21. |
- Busse, W. W., et al.
(författare)
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Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the beta(2) agonist vilanterol administered once daily for 52 weeks in patients >= 12 years old with asthma: a randomised trial
- 2013
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 68:6, s. 513-520
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Tidskriftsartikel (refereegranskat)abstract
- Background The inhaled corticosteroid fluticasone furoate (FF) in combination with the long-acting β2 agonist vilanterol (VI) is in development for asthma and chronic obstructive pulmonary disease. Objective To assess the safety and tolerability of FF/VI over 52weeks in patients with asthma. Methods Patients (aged ≥12years; on inhaled corticosteroid) were randomised (2:2:1) to FF/VI 100/25µg or FF/VI 200/25µg once daily in the evening, or fluticasone propionate (FP) 500µg twice daily. Safety evaluations included adverse events (AEs), non-fasting glucose, potassium, 24-h urinary cortisol excretion, ophthalmic assessments, heart rate and pulse rate. Results On-treatment AEs were similar across groups (FF/VI 66–69%; 73% FP). Oral candidiasis/oropharyngeal candidiasis was more common with FF/VI (6–7%) than FP (3%). Twelve serious AEs were reported; one (worsening hepatitis B on FP) was considered drug related. Statistically significant cortisol suppression was seen with FP compared with both FF/VI groups at Weeks 12 and 28 (ratios [95% CI] to FP ranged from 1.43 [1.11 to 1.84] to 1.67 [1.34 to 2.08]; p≤0.006), but not at Week 52 (ratios to FP were 1.05 [0.83 to 1.33] for FF/VI 100/25µg and 1.09 [0.87 to 1.38] for FF/VI 200/25µg). No clinically important changes in non-fasting glucose, potassium, QT interval corrected using Fridericia's formula (QTc[F]) or ophthalmic assessments were reported. Pulse rate (10min post dose [Tmax], Week 52) was significantly increased with FF/VI versus FP (3.4bpm, 95% CI 1.3 to 5.6; p=0.002 [FF/VI 100/25µg]; 3.4bpm, 95% CI 1.2 to 5.6; p=0.003 [FF/VI 200/25µg]). Mean heart rate (24-h Holter monitoring) decreased from screening values in all groups (0.2–1.1bpm FF/VI vs 5bpm FP; Week 52). Conclusions FF/VI (100/25µg or 200/25µg) administered once daily over 52weeks was well tolerated by patients aged ≥12years with asthma. The overall safety profile of FF/VI did not reveal any findings of significant clinical concern.
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| 22. |
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| 23. |
- Erickson, Andrew, et al.
(författare)
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The spatial landscape of clonal somatic mutations in benign and malignant tissue
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. Here, we provide an unsupervised approach to study spatial genome integrity in situ to gain molecular insight into clonal relationships. We employed spatially resolved transcriptomics to infer spatial copy number variations in >120 000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
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| 24. |
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| 25. |
- Garcia, L, et al.
(författare)
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Non-occupational physical activity and risk of cardiovascular disease, cancer and mortality outcomes: a dose-response meta-analysis of large prospective studies
- 2023
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Ingår i: British journal of sports medicine. - : BMJ. - 1473-0480 .- 0306-3674. ; 57:15, s. 979-
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Tidskriftsartikel (refereegranskat)abstract
- To estimate the dose–response associations between non-occupational physical activity and several chronic disease and mortality outcomes in the general adult population.DesignSystematic review and cohort-level dose-response meta-analysis.Data sourcesPubMed, Scopus, Web of Science and reference lists of published studies.Eligibility criteriaProspective cohort studies with (1) general population samples >10 000 adults, (2) ≥3 physical activity categories, and (3) risk measures and CIs for all-cause mortality or incident total cardiovascular disease, coronary heart disease, stroke, heart failure, total cancer and site-specific cancers (head and neck, myeloid leukaemia, myeloma, gastric cardia, lung, liver, endometrium, colon, breast, bladder, rectum, oesophagus, prostate, kidney).Results196 articles were included, covering 94 cohorts with >30 million participants. The evidence base was largest for all-cause mortality (50 separate results; 163 415 543 person-years, 811 616 events), and incidence of cardiovascular disease (37 results; 28 884 209 person-years, 74 757 events) and cancer (31 results; 35 500 867 person-years, 185 870 events). In general, higher activity levels were associated with lower risk of all outcomes. Differences in risk were greater between 0 and 8.75 marginal metabolic equivalent of task-hours per week (mMET-hours/week) (equivalent to the recommended 150 min/week of moderate-to-vigorous aerobic physical activity), with smaller marginal differences in risk above this level to 17.5 mMET-hours/week, beyond which additional differences were small and uncertain. Associations were stronger for all-cause (relative risk (RR) at 8.75 mMET-hours/week: 0.69, 95% CI 0.65 to 0.73) and cardiovascular disease (RR at 8.75 mMET-hours/week: 0.71, 95% CI 0.66 to 0.77) mortality than for cancer mortality (RR at 8.75 mMET-hours/week: 0.85, 95% CI 0.81 to 0.89). If all insufficiently active individuals had achieved 8.75 mMET-hours/week, 15.7% (95% CI 13.1 to 18.2) of all premature deaths would have been averted.ConclusionsInverse non-linear dose–response associations suggest substantial protection against a range of chronic disease outcomes from small increases in non-occupational physical activity in inactive adults.PROSPERO registration numberCRD42018095481.
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| 26. |
- Giménez-García, Angel, et al.
(författare)
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Pollination supply models from a local to global scale
- 2023
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Ingår i: Web Ecology. - 1399-1183. ; 23:2, s. 99-129
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Tidskriftsartikel (refereegranskat)abstract
- Ecological intensification has been embraced with great interest by the academic sector but is still rarely taken up by farmers because monitoring the state of different ecological functions is not straightforward. Modelling tools can represent a more accessible alternative of measuring ecological functions, which could help promote their use amongst farmers and other decision-makers. In the case of crop pollination, modelling has traditionally followed either a mechanistic or a data-driven approach. Mechanistic models simulate the habitat preferences and foraging behaviour of pollinators, while data-driven models associate georeferenced variables with real observations. Here, we test these two approaches to predict pollination supply and validate these predictions using data from a newly released global dataset on pollinator visitation rates to different crops. We use one of the most extensively used models for the mechanistic approach, while for the data-driven approach, we select from among a comprehensive set of state-of-The-Art machine-learning models. Moreover, we explore a mixed approach, where data-derived inputs, rather than expert assessment, inform the mechanistic model. We find that, at a global scale, machine-learning models work best, offering a rank correlation coefficient between predictions and observations of pollinator visitation rates of 0.56. In turn, the mechanistic model works moderately well at a global scale for wild bees other than bumblebees. Biomes characterized by temperate or Mediterranean forests show a better agreement between mechanistic model predictions and observations, probably due to more comprehensive ecological knowledge and therefore better parameterization of input variables for these biomes. This study highlights the challenges of transferring input variables across multiple biomes, as expected given the different composition of species in different biomes. Our results provide clear guidance on which pollination supply models perform best at different spatial scales-the first step towards bridging the stakeholder-Academia gap in modelling ecosystem service delivery under ecological intensification.
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| 27. |
- Gore, C., et al.
(författare)
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Treatment and secondary prevention effects of the probiotics Lactobacillus paracasei or Bifidobacterium lactis on early infant eczema : randomized controlled trial with follow-up until age 3 years
- 2012
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 42:1, s. 112-122
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Tidskriftsartikel (refereegranskat)abstract
- Background Allergic disease has been associated with altered intestinal microbiota. Therefore, probiotics have been suggested as a potential treatment for eczema. Objective We investigated whether dietary supplementation of infants with eczema at age 3-6 months with Lactobacillus paracasei CNCM I-2116 or Bifidobacterium lactis CNCM I3446 had a treatment effect or altered allergic disease progression. Methods Primary outcome included eczema severity (SCORing Atopic Dermatitis, SCORAD) 3 months post-randomization. Secondary: SCORAD (other visits); infant dermatitis quality of life (IDQoL); gastrointestinal permeability; urinary eosinophilic protein X; allergen- sensitization; allergic symptoms (age 12, 18, 36 months). A total of 208 infants aged 3-6 months with physician-diagnosed eczema were recruited; 137/208 (SCORAD >= 10, consuming >= 200 mL standard formula/day) were randomized to daily supplements containing L. paracasei or B. lactis or placebo for a 3-month period, while receiving extensively hydrolysed whey-formula (dairy-free diet). There were two open observational groups, one group exclusively breastfed (n = 22) and the other, standard formula-fed (n = 49). Trial number: ISRCTN41490500. Results Eczema severity decreased significantly over time in all groups. No significant difference was observed between randomized groups after 12-week treatment-period (SCORAD-score pre-/post-intervention: B. lactis 25.9 [95% CI: 22.8-29.2] to 12.8 [9.416.6]; L. paracasei 25.4 [22.1-29] to 12.5 [9.2-16.4]; placebo 26.9 [23.4-30.6] to 11.8 [9.6-14.3]; P = 0.7). Results were similar when analysis was controlled for allergen-sensitization, or when only sensitized infants were analysed. No differences were found for secondary outcomes. No difference was observed in SCORAD-score between randomized and observational groups. Conclusion and Clinical Relevance We found no benefit from supplementation with B. lactis or L. paracasei in the treatment of eczema, when given as an adjunct to basic topical treatment, and no effect on the progression of allergic disease from age 1 to 3 years.
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| 28. |
- Haigh, Daisy B., et al.
(författare)
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The METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer
- 2022
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 14:20
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer (PCa) is a leading cause of cancer-related deaths and is driven by aberrant androgen receptor (AR) signalling. For this reason, androgen deprivation therapies (ADTs) that suppress androgen-induced PCa progression either by preventing androgen biosynthesis or via AR signalling inhibition (ARSi) are common treatments. The N6-methyladenosine (m6A) RNA modification is involved in regulating mRNA expression, translation, and alternative splicing, and through these mechanisms has been implicated in cancer development and progression. RNA-m6A is dynamically regulated by the METTL3 RNA methyltransferase complex and the FTO and ALKBH5 demethylases. While there is evidence supporting a role for aberrant METTL3 in many cancer types, including localised PCa, the wider contribution of METTL3, and by inference m6A, in androgen signalling in PCa remains poorly understood. Therefore, the aim of this study was to investigate the expression of METTL3 in PCa patients and study the clinical and functional relevance of METTL3 in PCa. It was found that METTL3 is aberrantly expressed in PCa patient samples and that siRNA-mediated METTL3 knockdown or METTL3-pharmacological inhibition significantly alters the basal and androgen-regulated transcriptome in PCa, which supports targeting m6A as a novel approach to modulate androgen signalling in PCa.
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| 29. |
- Hampel, Harald, et al.
(författare)
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Biomarkers for Alzheimer's disease: academic, industry and regulatory perspectives.
- 2010
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Ingår i: Nature reviews. Drug discovery. - : Springer Science and Business Media LLC. - 1474-1784 .- 1474-1776. ; 9:7, s. 560-74
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Forskningsöversikt (refereegranskat)abstract
- Advances in therapeutic strategies for Alzheimer's disease that lead to even small delays in onset and progression of the condition would significantly reduce the global burden of the disease. To effectively test compounds for Alzheimer's disease and bring therapy to individuals as early as possible there is an urgent need for collaboration between academic institutions, industry and regulatory organizations for the establishment of standards and networks for the identification and qualification of biological marker candidates. Biomarkers are needed to monitor drug safety, to identify individuals who are most likely to respond to specific treatments, to stratify presymptomatic patients and to quantify the benefits of treatments. Biomarkers that achieve these characteristics should enable objective business decisions in portfolio management and facilitate regulatory approval of new therapies.
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| 30. |
- Harris, Anna E., et al.
(författare)
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Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer
- 2022
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 13
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Forskningsöversikt (refereegranskat)abstract
- Androgen deprivation therapies (ADTs) are important treatments which inhibit androgen-induced prostate cancer (PCa) progression by either preventing androgen biosynthesis (e.g. abiraterone) or by antagonizing androgen receptor (AR) function (e.g. bicalutamide, enzalutamide, darolutamide). A major limitation of current ADTs is they often remain effective for limited durations after which patients commonly progress to a lethal and incurable form of PCa, called castration-resistant prostate cancer (CRPC) where the AR continues to orchestrate pro-oncogenic signalling. Indeed, the increasing numbers of ADT-related treatment-emergent neuroendocrine-like prostate cancers (NePC), which lack AR and are thus insensitive to ADT, represents a major therapeutic challenge. There is therefore an urgent need to better understand the mechanisms of AR action in hormone dependent disease and the progression to CRPC, to enable the development of new approaches to prevent, reverse or delay ADT-resistance. Interestingly the AR regulates distinct transcriptional networks in hormone dependent and CRPC, and this appears to be related to the aberrant function of key AR-epigenetic coregulator enzymes including the lysine demethylase 1 (LSD1/KDM1A). In this review we summarize the current best status of anti-androgen clinical trials, the potential for novel combination therapies and we explore recent advances in the development of novel epigenetic targeted therapies that may be relevant to prevent or reverse disease progression in patients with advanced CRPC.
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| 31. |
- Lötvall, Jan, 1956, et al.
(författare)
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24-h duration of the novel LABA vilanterol trifenatate in asthma patients treated with inhaled corticosteroids
- 2012
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 40:3, s. 570-579
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Tidskriftsartikel (refereegranskat)abstract
- Current guidelines recommend adding a long-acting inhaled beta(2)-agonist (LABA) to inhaled corticosteroids (ICS) in patients with uncontrolled asthma. This study evaluated the novel, once-daily LABA vilanterol trifenatate (VI) in asthma patients who remained symptomatic despite existing ICS therapy. The study involved a randomised, double-blind, placebo-controlled trial of VI (3, 6.25, 12.5, 25 and 50 mu g), administered once daily in the evening by dry powder inhaler for 28 days, in asthma patients aged >= 12 yrs symptomatic on current ICS therapy. The primary end-point was trough (24 h post-dose) forced expiratory volume in 1 s (FEV1); secondary end-points were weighted mean FEV1, peak expiratory flow (PEF), symptom-/rescue-free 24-h periods, and safety. A significant relationship was observed between VI dose and improvements in trough FEV1 (p=0.037). Statistically significant increases in mean trough FEV1, relative to placebo, were documented for VI 12.5-50 mu g (121-162 mL; p <= 0.016). Dose-related effects of VI were observed on weighted mean (0-24 h) FEV1, morning/evening PEF, and symptom-/rescue-free 24-h periods. All doses of VI were well tolerated with low incidences of recognised LABA-related adverse events (tremor 0-2%; palpitations 0-2%; glucose effects 0-1%; potassium effects 0-<1%). Once-daily VI 12.5-50 mu g resulted in prolonged bronchodilation of at least 24 h with good tolerability in asthma patients receiving ICS. Based on the overall efficacy and adverse event profile from this study, the optimum dose of VI appears to be 25 mg.
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| 32. |
- Martin, Maria A., et al.
(författare)
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Ten new insights in climate science 2021 : a horizon scan
- 2021
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Ingår i: Global Sustainability. - : Cambridge University Press (CUP). - 2059-4798. ; 4, s. 1-20
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Forskningsöversikt (refereegranskat)abstract
- Non-technical summary: We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding about the remaining options to achieve the Paris Agreement goals, through overcoming political barriers to carbon pricing, taking into account non-CO2 factors, a well-designed implementation of demand-side and nature-based solutions, resilience building of ecosystems and the recognition that climate change mitigation costs can be justified by benefits to the health of humans and nature alone. We consider new insights about what to expect if we fail to include a new dimension of fire extremes and the prospect of cascading climate tipping elements.Technical summary: A synthesis is made of 10 topics within climate research, where there have been significant advances since January 2020. The insights are based on input from an international open call with broad disciplinary scope. Findings include: (1) the options to still keep global warming below 1.5 °C; (2) the impact of non-CO2 factors in global warming; (3) a new dimension of fire extremes forced by climate change; (4) the increasing pressure on interconnected climate tipping elements; (5) the dimensions of climate justice; (6) political challenges impeding the effectiveness of carbon pricing; (7) demand-side solutions as vehicles of climate mitigation; (8) the potentials and caveats of nature-based solutions; (9) how building resilience of marine ecosystems is possible; and (10) that the costs of climate change mitigation policies can be more than justified by the benefits to the health of humans and nature.Social media summary: How do we limit global warming to 1.5 °C and why is it crucial? See highlights of latest climate science.
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| 33. |
- Metzler, Veronika M., et al.
(författare)
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The KDM5B and KDM1A lysine demethylases cooperate in regulating androgen receptor expression and signalling in prostate cancer
- 2023
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Ingår i: Frontiers in Cell and Developmental Biology. - : Frontiers Media S.A.. - 2296-634X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Histone H3 lysine 4 (H3K4) methylation is key epigenetic mark associated with active transcription and is a substrate for the KDM1A/LSD1 and KDM5B/JARID1B lysine demethylases. Increased expression of KDM1A and KDM5B is implicated in many cancer types, including prostate cancer (PCa). Both KDM1A and KDM5B interact with AR and promote androgen regulated gene expression. For this reason, there is great interested in the development of new therapies targeting KDM1A and KDM5B, particularly in the context of castrate resistant PCa (CRPC), where conventional androgen deprivation therapies and androgen receptor signalling inhibitors are no longer effective. As there is no curative therapy for CRPC, new approaches are urgently required to suppress androgen signalling that prevent, delay or reverse progression to the castrate resistant state. While the contribution of KDM1A to PCa is well established, the exact contribution of KDM5B to PCa is less well understood. However, there is evidence that KDM5B is implicated in numerous pro-oncogenic mechanisms in many different types of cancer, including the hypoxic response, immune evasion and PI3/AKT signalling. Here we elucidate the individual and cooperative functions of KDM1A and KDM5B in PCa. We show that KDM5B mRNA and protein expression is elevated in localised and advanced PCa. We show that the KDM5 inhibitor, CPI-455, impairs androgen regulated transcription and alternative splicing. Consistent with the established role of KDM1A and KDM5B as AR coregulators, we found that individual pharmacologic inhibition of KDM1A and KDM5 by namoline and CPI-455 respectively, impairs androgen regulated transcription. Notably, combined inhibition of KDM1A and KDM5 downregulates AR expression in CRPC cells. Furthermore, combined KDM1A and KDM5 inhibition impairs PCa cell proliferation and invasion more than individual inhibition of KDM1A and KDM5B. Collectively our study has identified individual and cooperative mechanisms involving KDM1A and KDM5 in androgen signalling in PCa. Our findings support the further development of KDM1A and KDM5B inhibitors to treat advanced PCa. Further work is now required to confirm the therapeutic feasibility of combined inhibition of KDM1A and KDM5B as a novel therapeutic strategy for targeting AR positive CRPC.
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| 34. |
- Ou, L. C., et al.
(författare)
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A cross-cultural comparison of colour emotion for two-colour combinations
- 2012
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Ingår i: Color Research and Application. - : Wiley. - 1520-6378 .- 0361-2317. ; 37:1, s. 23-43
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Tidskriftsartikel (refereegranskat)abstract
- Psychophysical experiments were conducted in the UK, Taiwan, France, Germany, Spain, Sweden, Argentina, and Iran to assess colour emotion for two-colour combinations using semantic scales warm/cool, heavy/light, active/passive, and like/dislike. A total of 223 observers participated, each presented with 190 colour pairs as the stimuli, shown individually on a cathode ray tube display. The results show consistent responses across cultures only for warm/cool, heavy/light, and active/passive. The like/dislike scale, however, showed some differences between the observer groups, in particular between the Argentinian responses and those obtained from the other observers. Factor analysis reveals that the Argentinian observers preferred passive colour pairs to active ones more than the other observers. In addition to the cultural difference in like/dislike, the experimental results show some effects of gender, professional background (design vs. nondesign), and age. Female observers were found to prefer colour pairs with high-lightness or low-chroma values more than their male counterparts. Observers with a design background liked low-chroma colour pairs or those containing colours of similar hue more than nondesign observers. Older observers liked colour pairs with high-lightness or high-chroma values more than young observers did. Based on the findings, a two-level theory of colour emotion is proposed, in which warm/cool, heavy/light, and active/passive are identified as the reactive-level responses and like/dislike the reflective-level response.
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| 35. |
- Patke, Rodhan, et al.
(författare)
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Epitranscriptomic mechanisms of androgen signalling and prostate cancer
- 2024
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Ingår i: Neoplasia. - : Elsevier. - 1522-8002 .- 1476-5586. ; 56
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Forskningsöversikt (refereegranskat)abstract
- Prostate cancer (PCa) is the second most common cancer diagnosed in men. While radical prostatectomy and radiotherapy are often successful in treating localised disease, post-treatment recurrence is common. As the androgen receptor (AR) and androgen hormones play an essential role in prostate carcinogenesis and progression, androgen deprivation therapy (ADT) is often used to deprive PCa cells of the pro-proliferative effect of androgens. ADTs act by either blocking androgen biosynthesis (e.g. abiraterone) or blocking AR function (e.g. bicalutamide, enzalutamide, apalutamide, darolutamide). ADT is often effective in initially suppressing PCa growth and progression, yet emergence of castrate-resistant PCa and progression to neuroendocrine-like PCa following ADT are major clinical challenges. For this reason, there is an urgent need to identify novel approaches to modulate androgen signalling to impede PCa progression whilst also preventing or delaying therapy resistance. The mechanistic convergence of androgen and epitranscriptomic signalling offers a potential novel approach to treat PCa. The epitranscriptome involves covalent modifications of mRNA, notably, in the context of this review, the N(6)-methyladenosine (m6A) modification. m6A is involved in the regulation of mRNA splicing, stability, and translation, and has recently been shown to play a role in PCa and androgen signalling. The m6A modification is dynamically regulated by the METTL3-containing methyltransferase complex, and the FTO and ALKBH5 RNA demethylases. Given the need for novel approaches to treat PCa, there is significant interest in new therapies that target m6A that modulate AR expression and androgen signalling. This review critically summarises the potential benefit of such epitranscriptomic therapies for PCa patients.
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| 36. |
- Persson Waye, Kerstin, 1959, et al.
(författare)
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Assessing the exposure-response relationship of sleep disturbance and vibration in field and laboratory settings
- 2019
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Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491. ; 245, s. 558-567
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to nocturnal freight train vibrations may impact sleep, but exposure-response relationships are lacking. The European project CargoVibes evaluated sleep disturbance both in the field and in the laboratory and provides unique data, as measures of response and exposure metrics are comparable. This paper therefore provides data on exposure-response relationships of vibration and sleep disturbance and compares the relationships evaluated in the laboratory and the field. Two field studies (one in Poland and one in the Netherlands) with 233 valid respondents in total, and three laboratory studies in Sweden with a total of 59 subjects over 350 person-nights were performed. The odds ratios (OR) of sleep disturbance were analyzed in relation to nighttime vibration exposure by ordinal logit regression, adjusting for moderating factors common for the studies. Outcome specific fractions were calculated for eleven sleep outcomes and supported comparability between the field and laboratory settings. Vibration exposure was significantly associated with sleep disturbance, OR = 3.51 (95% confidence interval 2.6–4.73) denoting a three and a half times increase in the odds of sleep disturbance with one unit increased 8 h nighttime log10 Root Mean Square vibration. The results suggest no significant difference between field and laboratory settings OR = 1.37 (0.59–3.19). However, odds of sleep disturbance were higher in the Netherlands as compared to Sweden, indicating unexplained differences between study populations or countries, possibly related to cultural and contextual differences and uncertainties in exposure assessments. Future studies should be carefully designed to record explanatory factors in the field and enhance ecological validity in the laboratory. Nevertheless, the presented combined data set provides a first set of exposure response relationships for vibration-induced sleep disturbance, which are useful when considering public health outcomes among exposed populations. Exposure-response relationships of vibration exposure from trains and sleep disturbance were derived from laboratory studies and field studies, with no significant differences between the settings. © 2018 The Authors
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| 37. |
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| 38. |
- Susilo, Yusak O., et al.
(författare)
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Findings from measuring door-to-door travellers’ travel satisfaction with traditional and smartphone app survey methods in eight European cities
- 2017
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Ingår i: European Journal of Transport and Infrastructure Research. - : Editorial Board EJTIR. - 1567-7133 .- 1567-7141. ; 17:3, s. 384-410
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates how different travel satisfaction survey methods influence the reported level of door-to-door travel satisfaction among travellers. The travel satisfaction measurement survey tools tested consisted of two types of smartphone applications (a satellite navigation app and a game app), an on-line survey, a paper-based semi-structured questionnaire and a focus group. Each of the measurement tools comprised of a similar set of questions, but in different formats, aimed at exploring the pros and cons of each tool among different group of travellers. In total, 5,275 valid responses were collected during the survey period from eight European cities and five FIA (Federation Internationale de I’Automobile) national motorist networks. The analysis results, with ordered logit model of travellers’ reported overall satisfaction, showed that the travel satisfaction reported by different survey methods and different travel modes and user groups, correlated with distinct groups of key determinants. The relationship between and within these key determinants, however, was far from straight forward. Some were more complex than others. Some issues, such as parking availability and security, that are mostly discussed by policy makers and users may not be the ones that directly correlate with the users’ overall travel satisfactions. Consistent with previous studies, the travellers’ mood and previous experience influenced the reported overall journey satisfaction.
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| 39. |
- Woodcock, K., et al.
(författare)
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τ9Eri : a bright pulsating magnetic Bp star in a 5.95-d double-lined spectroscopic binary
- 2021
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 502:4, s. 5200-5209
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Tidskriftsartikel (refereegranskat)abstract
- tau(9)Eri is a Bp star that was previously reported to be a single-lined spectroscopic binary. Using 17 ESPaDOnS spectropolarimetric (Stokes V) observations, we identified the weak spectral lines of the secondary component and detected a strong magnetic field in the primary. We performed orbital analysis of the radial velocities of both components to find a slightly eccentric orbit (e = 0.129) with a period of 5.95382(2) d. The longitudinal magnetic field (B-l) of the primary was measured from each of the Stokes V profiles, with typical error bars smaller than 10 G. Equivalent widths (EWs) of least-squares deconvolution profiles corresponding to only the Fe lines were also measured. We performed frequency analysis of both the B-l and EW measurements, as well as of the Hipparcos, SMEI, and TESS photometric data. All sets of photometric observations produce two clear, strong candidates for the rotation period of the Bp star: 1.21 and 3.82 d. The B-l and EW measurements are consistent with only the 3.82-d period. We conclude that HD25267 consists of a late-type Bp star (M = 3.6(-0.2)(+0.1)M(circle dot), T = 12580(-120)(+150) K) with a rotation period of 3.82262(4) d orbiting with a period of 5.95382(2) d with a late-A/early-F type secondary companion (M = 1.6 +/- 0.1 M-circle dot, T = 7530(-510)(+580) K). The Bp star's magnetic field is approximately dipolar with i = 41 +/- 2 degrees, beta = 158 +/- 5 degrees, and B-d = 1040 +/- 50 G. All evidence points to the strong 1.209912(3)-d period detected in photometry, along with several other weaker photometric signals, as arising from g-mode pulsations in the primary.
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