| 1. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 2. |
- Dans, Madeline G., et al.
(författare)
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Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite’s lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action.
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| 3. |
- Hogan, Kelly A., et al.
(författare)
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Glacial sedimentation, fluxes and erosion rates associated with ice retreat in Petermann Fjord and Nares Strait, north-west Greenland
- 2020
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Ingår i: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 14:1, s. 261-286
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Tidskriftsartikel (refereegranskat)abstract
- Petermann Fjord is a deep ( > 1000 m) fjord that incises the coastline of north-west Greenland and was carved by an expanded Petermann Glacier, one of the six largest outlet glaciers draining the modern Greenland Ice Sheet (GrIS). Between 5 and 70 m of unconsolidated glacigenic material infills in the fjord and adjacent Nares Strait, deposited as the Petermann and Nares Strait ice streams retreated through the area after the Last Glacial Maximum. We have investigated the deglacial deposits using seismic stratigraphic techniques and have correlated our results with high-resolution bathymetric data and core lithofacies. We identify six seismoacoustic facies in more than 3500 line kilometres of subbottom and seismic-reflection profiles throughout the fjord, Hall Basin and Kennedy Channel. Seismo-acoustic facies relate to bedrock or till surfaces (Facies I), subglacial deposition (Facies II), deposition from meltwater plumes and icebergs in quiescent glacimarine conditions (Facies III, IV), deposition at grounded ice margins during stillstands in retreat (grounding-zone wedges; Facies V) and the redeposition of material downslope (Facies IV). These sediment units represent the total volume of glacial sediment delivered to the mapped marine environment during retreat. We calculate a glacial sediment flux for the former Petermann ice stream as 1080-1420 m(3) a(-1) per metre of ice stream width and an average deglacial erosion rate for the basin of 0.29-0.34 mm a(-1). Our deglacial erosion rates are consistent with results from Antarctic Peninsula fjord systems but are several times lower than values for other modern GrIS catchments. This difference is attributed to fact that large volumes of surface water do not access the bed in the Petermann system, and we conclude that glacial erosion is limited to areas overridden by streaming ice in this large outlet glacier setting. Erosion rates are also presented for two phases of ice retreat and confirm that there is significant variation in rates over a glacial-deglacial transition. Our new glacial sediment fluxes and erosion rates show that the Petermann ice stream was approximately as efficient as the palaeo-Jakobshavn Isbra at eroding, transporting and delivering sediment to its margin during early deglaciation.
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| 4. |
- Jennings, Anne, et al.
(författare)
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Modern and early Holocene ice shelf sediment facies from Petermann Fjord and northern Nares Strait, northwest Greenland
- 2022
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 283
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Tidskriftsartikel (refereegranskat)abstract
- Based on sediment cores and geophysical data collected from Petermann Fjord and northern Nares Strait, NW Greenland, an Arctic ice shelf sediment facies is presented that distinguishes sub and pro ice shelf environments. Sediment cores were collected from sites beneath the present day Petermann Ice Tongue (PIT) and in deglacial sediments of northern Nares Strait with a focus on understanding the glacial and oceanographic history over the last 11,000 cal yr BP. The modern sub ice shelf sediment facies in Petermann Fjord is laminated and devoid of coarse clasts (IRD) due to strong basal melting that releases debris (debris filtering) from the basal ice at the grounding zone driven by buoyant subglacial meltwater and entrained Atlantic Water. Laminated sediments in the deep basin proximal to the gounding zone comprise layers of fine mud formed by suspension settling from turbid meltwater plumes (plumites) interrupted by normally graded very fine sand to medium silt layers with sharp basal contacts and rip-up clasts of mud, interpreted as turbidites. An inner fjord sill limits distribution of sediment gravity flows from the grounding zone to the deep inner fjord basin, such that sites on the inner sill and beyond the ice tongue largely only comprise plumites. Bioturbation and foraminiferal abundances increase with distance from the grounding zone. The benthic foraminiferal species, Elphidium clavatum is absent beneath the ice tongue, but dominant in the turbid meltwater influenced environment beyond the ice tongue. The very sparse IRD in sediments beneath the PIT and in the fjord beyond the PIT derives mainly from englacial debris in the ice tongue, side valley glaciers, rock falls from the steep fjord walls and sea ice.We use the modern ice shelf sediment facies characteristics to infer the past presence of ice shelves in northern Nares Strait using analyses of sediment cores from several cruises (OD1507, HLY03, 2001LSSL, RYDER19). On bathymetric highs, bioturbated mud with dispersed IRD overlies a 10–15 m thick, distinctly laminated silt and clay unit with rare coarse clasts and sparse foraminifera which forms a sediment drape of nearly uniform thickness. We interpret these laminated sediments to represent glaciomarine deposition by meltwater plumes emanating from ice streams that terminated in floating ice shelves. IRD layers, shifts in sediment composition (qXRD, MS and XRF) and faunal assemblage changes in the laminated unit document periods of ice-shelf instability sometimes, but not always, coupled with grounding zone retreat. Our deglacial reconstruction, including ice shelves, begins ∼10.7 cal ka BP, with confluent ice streams grounded in Hall Basin fronted by the Robeson Channel ice shelf. Ice shelf breakup and grounding zone retreat to relatively stable grounding zones at Kennedy Channel and the mouth of Petermann Fjord was accomplished by 9.4 cal ka BP when the Hall Basin ice shelf was established. This ice shelf broke up and reformed once prior to the final break up at 8.5 to 8.4 cal ka BP marking ice stream collapse, separation of Greenland and Innuitian ice sheets, and the opening of Nares Strait for Arctic-Atlantic throughflow. The Petermann ice shelf remained in Hall Basin until the Petermann Glacier retreated from the fjord mouth ∼7.1 cal ka BP. The resilience of these northern ice streams to strong early Holocene insolation and subsurface Atlantic Water advection is attributed to their northern aspect, buttressing by narrow passages, and high ice flux from the Greenland Ice Sheet (GIS).
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| 5. |
- Matas, Julia, et al.
(författare)
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Colorectal Cancer Is Associated with the Presence of Cancer Driver Mutations in Normal Colon
- 2022
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Ingår i: Cancer Research. - : American Association for Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 82:8, s. 1492-1502
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Tidskriftsartikel (refereegranskat)abstract
- Although somatic mutations in colorectal cancer are well characterized, little is known about the accumulation of cancer mutations in the normal colon before cancer. Here, we have developed and applied an ultrasensitive, single-molecule mutational test based on CRISPR-DS technology, which enables mutation detection at extremely low frequency (< 0.001) in normal colon from patients with and without colorectal cancer. This testing platform revealed that normal colon from patients with and without colorectal cancer carries mutations in common colorectal cancer genes, but these mutations are more abundant in patients with cancer. Oncogenic KRAS mutations were observed in the normal colon of about one third of patients with colorectal cancer but in none of the patients without colorectal cancer. Patients with colorectal cancer also carried more TP53 mutations than patients without cancer and these mutations were more pathogenic and formed larger clones, especially in patients with early-onset colorectal cancer. Most mutations in the normal colon were different from the driver mutations in tumors, suggesting that the occurrence of independent clones with pathogenic KRAS and TP53 mutations is a common event in the colon of individuals who develop colorectal cancer. These results indicate that somatic evolution contributes to clonal expansions in the normal colon and that this process is enhanced in individuals with cancer, particularly in those with early-onset colorectal cancer. Significance: This work suggests prevalent somatic evolution in the normal colon of patients with colorectal cancer, highlighting the potential of using ultrasensitive gene sequencing to predict disease risk. [GRAPHICS]
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| 6. |
- Nilsson, Anna, et al.
(författare)
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The European Court’s Incremental Approach to the Protection of Liberty, Dignity and Autonomy
- 2023
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Ingår i: Routledge Handbook of Mental Health Law. - 9781003226413
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Mental health law is inextricably connected to key human rights protected under the European Convention on Human Rights (1950, ECHR or the Convention), such as the right to freedom of liberty, to personal autonomy and physical and mental integrity, and to the right to not be discriminated against. This chapter outlines the fundamental procedural and substantive standards developed by the European Court of Human Rights (ECtHR or the Court) in its jurisprudence relating to these rights. It pays attention to the level of judicial scrutiny the Court has applied in cases involving mental health care provision and points to a trend towards stricter scrutiny in such cases. It also includes a discussion of the Court's response to the development of human rights standards in the context of mental health that has taken place in relation to the UN Convention on the Rights of Persons with Disabilities (CRPD), and ends with a call on the Court to engage in discrimination analysis and to consider introducing positive obligations on states parties to develop voluntary crisis support services in order to prevent human rights violations associated with compulsory mental health interventions.
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| 7. |
- Striano, Brendan M, et al.
(författare)
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Displaced Supracondylar Humerus Fractures in Toddlers
- 2020
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Ingår i: Orthopedics. - : SLACK, Inc.. - 1938-2367 .- 0147-7447. ; 43:5, s. 421-424
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Tidskriftsartikel (refereegranskat)abstract
- Gartland type III fracture is the most troublesome type of supracondylar humerus fracture. These injuries most often occur in school age children, but they are seen in pediatric patients of all ages. The goal of this study was to analyze toddlers with Gartland type III fractures to identify clinically significant differences compared with older children. A retrospective cohort study was conducted with 94 toddlers (<3 years) and 378 older children (3 to 12 years). Factors including demographics, mechanism of injury, additional injuries, location of trauma, pin configuration, postoperative complications, follow-up time, and compliance with the treatment plan were collected and compared. The study included 94 toddlers (59% girls, 2.11±0.64 years) and 378 older children (48% girls, 6.32±1.89 years), chosen at random, who were treated between 2000 and 2015. Among toddlers, fractures were more likely to occur at home (P<.001) and to be the result of suspected nonaccidental trauma (P<.001). Older children had more additional injuries (P<.001), but were no more likely to have an open fracture (P=.59) or a flexion-type fracture (P=.42). Older children were more likely to undergo open reduction (P=.03), whereas toddlers were more likely to be treated with a medial pin (P<.001). Toddlers experienced more cubitus varus (P<.001) and loss of reduction (P=.02). No difference was found in length of follow-up (P=.83) or compliance with the treatment plan (P=.11). This study provides novel insights into clinical differences between toddlers and older children with Gartland type III fractures. Knowledge of these differences can facilitate the delivery of targeted, age-specific care for patients with type III supracondylar humerus fractures. [Orthopedics. 2020;43(5);e421-e424.].
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| 8. |
- Tedesco, Salvatore, et al.
(författare)
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Comparison of machine learning techniques for mortality prediction in a prospective cohort of older adults
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 18:23
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Tidskriftsartikel (refereegranskat)abstract
- As global demographics change, ageing is a global phenomenon which is increasingly of interest in our modern and rapidly changing society. Thus, the application of proper prognostic indices in clinical decisions regarding mortality prediction has assumed a significant importance for personalized risk management (i.e., identifying patients who are at high or low risk of death) and to help ensure effective healthcare services to patients. Consequently, prognostic modelling expressed as all‐cause mortality prediction is an important step for effective patient management. Machine learning has the potential to transform prognostic modelling. In this paper, results on the development of machine learning models for all‐cause mortality prediction in a cohort of healthy older adults are reported. The models are based on features covering anthropometric variables, physical and lab examinations, questionnaires, and lifestyles, as well as wearable data collected in free‐living settings, obtained for the “Healthy Ageing Initiative” study conducted on 2291 recruited participants. Several machine learning techniques including feature engineering, feature selection, data augmentation and resampling were investigated for this purpose. A detailed empirical comparison of the impact of the different techniques is presented and discussed. The achieved performances were also compared with a standard epidemiological model. This investigation showed that, for the dataset under consideration, the best results were achieved with Random Under‐ Sampling in conjunction with Random Forest (either with or without probability calibration). However, while including probability calibration slightly reduced the average performance, it increased the model robustness, as indicated by the lower 95% confidence intervals. The analysis showed that machine learning models could provide comparable results to standard epidemiological models while being completely data‐driven and disease‐agnostic, thus demonstrating the opportunity for building machine learning models on health records data for research and clinical practice. However, further testing is required to significantly improve the model performance and its robustness.
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| 9. |
- Tedesco, Salvatore, et al.
(författare)
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Investigation of the analysis of wearable data for cancer-specific mortality prediction in older adults
- 2021
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Ingår i: Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS. - : IEEE. - 9781728111797 ; , s. 1848-1851
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Konferensbidrag (refereegranskat)abstract
- Cancer is an aggressive disease which imparts a tremendous socio-economic burden on the international community. Early detection is an important aspect in improving survival rates for cancer sufferers; however, very few studies have investigated the possibility of predicting which people have the highest risk to develop this disease, even years before the traditional symptoms first occur. In this paper, a dataset from a longitudinal study which was collected among 2291 70-year olds in Sweden has been analyzed to investigate the possibility for predicting 2-7 year cancer-specific mortality. A tailored ensemble model has been developed to tackle this highly imbalanced dataset. The performance with different feature subsets has been investigated to evaluate the impact that heterogeneous data sources may have on the overall model. While a full-features model shows an Area Under the ROC Curve (AUC-ROC) of 0.882, a feature subset which only includes demographics, self-report health and lifestyle data, and wearable dataset collected in free-living environments presents similar performance (AUC-ROC: 0.857). This analysis confirms the importance of wearable technology for providing unbiased health markers and suggests its possible use in the accurate prediction of 2-7 year cancer-related mortality in older adults.
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| 10. |
- Tian, Ruiyi, et al.
(författare)
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Clonal Hematopoiesis and Risk of Incident Lung Cancer
- 2023
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X. ; 41:7, s. 1423-1433
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To prospectively examine the association between clonal hematopoiesis (CH) and subsequent risk of lung cancer. METHODS: Among 200,629 UK Biobank (UKBB) participants with whole-exome sequencing, CH was identified in a nested case-control study of 832 incident lung cancer cases and 3,951 controls (2006-2019) matched on age and year at blood draw, sex, race, and smoking status. A similar nested case-control study (141 cases/652 controls) was conducted among 27,975 participants with whole-exome sequencing in the Mass General Brigham Biobank (MGBB, 2010-2021). In parallel, we compared CH frequency in published data from 5,003 patients with solid tumor (2,279 lung cancer) who had pretreatment blood sequencing performed through Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets. RESULTS: In UKBB, the presence of CH was associated with increased risk of lung cancer (cases: 12.5% v controls: 8.7%; multivariable-adjusted odds ratio [OR], 1.36; 95% CI, 1.06 to 1.74). The association remained robust after excluding participants with chronic obstructive pulmonary disease. No significant interactions with known risk factors, including polygenic risk score and C-reactive protein, were identified. In MGBB, we observed similar enrichment of CH in lung cancer (cases: 15.6% v controls: 12.7%). The meta-analyzed OR (95% CI) of UKBB and MGBB was 1.35 (1.08 to 1.68) for CH overall and 1.61 (1.19 to 2.18) for variant allele frequencies ≥ 10%. In Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets, CH with a variant allele frequency ≥ 10% was enriched in pretreatment lung cancer compared with other tumors after adjusting for age, sex, and smoking (OR for lung v breast cancer: 1.61; 95% CI, 1.03 to 2.53). CONCLUSION: Independent of known risk factors, CH is associated with increased risk of lung cancer.
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