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11.
  • de Vries, Petrus J, et al. (författare)
  • Natural clusters of tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) : new findings from the TOSCA TAND research project
  • 2020
  • Ingår i: Journal of Neurodevelopmental Disorders. - : Springer Science and Business Media LLC. - 1866-1955 .- 1866-1947. ; 12:1, s. 24-24
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have unique, individual patterns that pose significant challenges for diagnosis, psycho-education, and intervention planning. A recent study suggested that it may be feasible to use TAND Checklist data and data-driven methods to generate natural TAND clusters. However, the study had a small sample size and data from only two countries. Here, we investigated the replicability of identifying natural TAND clusters from a larger and more diverse sample from the TOSCA study.METHODS: As part of the TOSCA international TSC registry study, this embedded research project collected TAND Checklist data from individuals with TSC. Correlation coefficients were calculated for TAND variables to generate a correlation matrix. Hierarchical cluster and factor analysis methods were used for data reduction and identification of natural TAND clusters.RESULTS: A total of 85 individuals with TSC (female:male, 40:45) from 7 countries were enrolled. Cluster analysis grouped the TAND variables into 6 clusters: a scholastic cluster (reading, writing, spelling, mathematics, visuo-spatial difficulties, disorientation), a hyperactive/impulsive cluster (hyperactivity, impulsivity, self-injurious behavior), a mood/anxiety cluster (anxiety, depressed mood, sleep difficulties, shyness), a neuropsychological cluster (attention/concentration difficulties, memory, attention, dual/multi-tasking, executive skills deficits), a dysregulated behavior cluster (mood swings, aggressive outbursts, temper tantrums), and an autism spectrum disorder (ASD)-like cluster (delayed language, poor eye contact, repetitive behaviors, unusual use of language, inflexibility, difficulties associated with eating). The natural clusters mapped reasonably well onto the six-factor solution generated. Comparison between cluster and factor solutions from this study and the earlier feasibility study showed significant similarity, particularly in cluster solutions.CONCLUSIONS: Results from this TOSCA research project in an independent international data set showed that the combination of cluster analysis and factor analysis may be able to identify clinically meaningful natural TAND clusters. Findings were remarkably similar to those identified in the earlier feasibility study, supporting the potential robustness of these natural TAND clusters. Further steps should include examination of larger samples, investigation of internal consistency, and evaluation of the robustness of the proposed natural clusters.
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12.
  • Frohlich, Miguel F., et al. (författare)
  • Legal barriers to adaptive coastal management at a coastal erosion hotspot in Florianópolis, Brazil
  • 2021
  • Ingår i: Marine Policy. - : Elsevier. - 0308-597X .- 1872-9460. ; 127
  • Tidskriftsartikel (refereegranskat)abstract
    • Adaptive management has long been promulgated as an appropriate approach to address the complexity and dynamics of coastal social-ecological systems. However, examples of successful implementation of this approach are still scarce. Law may be a factor hindering adaptive management, particularly when legal provisions are too rigid to enable change. Drawing on the management experience of Armaca similar to o Beach (a coastal erosion hotspot in the Municipality of Florian ' opolis, State of Santa Catarina, Brazil), this paper: (a) analyses how adaptive management has been used for coastal management in the selected study area and its applicable legal framework; and (b) identifies legal barriers to adaptive coastal management. Document analysis and semi-structured interviews with 27 participants were undertaken. An inductive thematic coding strategy was adopted to analyse interview data. Interpretation of results shows that coastal management in Florian ' opolis is yet to follow the structured and iterative learning process of adaptive management. Vague, imprecise, and generic legal provisions have contributed to reactive coastal management. In the context of open-ended legislation, government entities have used their legal discretion to avoid making coastal management plans, and short-term defence strategies to manage coastal erosion have proliferated in response to crisis situations. The paper highlights the importance of seeking the right balance between legal certainty and legal flexibility, providing an entry point to further research and legal reform discussions in the field of adaptive coastal management.
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13.
  • Frohlich, Miguel F., et al. (författare)
  • Towards adaptive coastal management : Lessons from a "legal storm" in Byron Shire, Australia
  • 2019
  • Ingår i: Ocean and Coastal Management. - : ELSEVIER SCI LTD. - 0964-5691 .- 1873-524X. ; 179
  • Tidskriftsartikel (refereegranskat)abstract
    • Adaptive management has been advocated as an appropriate approach for the management of social-ecological systems, although its implementation has proven to be a challenge. Legal systems can hinder or facilitate adaptive management. Focusing on legal arrangements, this article explores how adaptive management can be better operationalised in the context of coastal management. Byron Shire, a local government area in New South Wales, Australia, was selected as a case study where we: (a) analysed how the concept of adaptive management has emerged within the evolution of coastal management and its applicable legal framework, and (b) identified juridical constraints to adaptive coastal management. Qualitative methods were used for the analysis of relevant documents and semi-structured interviews with 23 key informants. The results show that a distorted version of adaptive management has been adopted in Byron Shire's draft coastal management plans, which fails to adhere to the formal, structured, and iterative process of adaptive management. A legacy created by the legal effects of past decisions affecting coastal management has led to a path dependency towards protective measures to manage coastal erosion, constraining other management options, particularly managed realignment strategies. Failure to address juridical constraints in the early stages of the adaptive management process can result in stakeholder conflict and litigation. Overlitigation harms adaptive coastal management by pushing the decision-making process away from the pathway offered by the legal framework for preparing and implementing coastal management plans. After recent legislative coastal reform at the state level, there is momentum for the Byron Shire Council to refocus its adaptive management approach. However, overcoming existing juridical constraints will require adaptive governance, in which all levels of government must work collaboratively with the affected stakeholders in the design and implementation of the adaptive management process.
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14.
  • Frohlich, Miguel, et al. (författare)
  • Towards adaptive coastal management law : Lessons from Australia and Brazil
  • 2022
  • Ingår i: Ocean and Coastal Management. - : Elsevier. - 0964-5691 .- 1873-524X. ; 219
  • Tidskriftsartikel (refereegranskat)abstract
    • Although adaptive management has been advocated for dealing with the complexity and dynamics of social ecological systems for more than 40 years, successful outcomes in practice have been limited. Among the efforts to overcome this implementation gap, there has been a growing interest in understanding the role of law in adaptive management. In this article, we provide an analysis of adaptive management in two jurisdictions struggling with coastal erosion in the context of their legal arrangements for coastal management: (i) Byron Shire, a local government area in the State of New South Wales, Australia; and (ii) Florian acute accent opolis, a municipality in the State of Santa Catarina, Brazil. Methods included document analysis and inductive thematic coding of 50 semi-structured interviews with key informants from four different stakeholder groups. Our results indicate that both legal certainty and legal flexibility are relevant for adaptive management success. Three directions towards coupling adaptive coastal management with law are suggested: (i) to incorporate adaptive management into coastal management legislation; (ii) to address legal path dependencies that cause maladaptation; and (iii) to integrate adaptive coastal management and adaptive coastal governance through adaptive coastal management law. Our suggestions contribute to improved knowledge on adaptive coastal management law by emphasising the need for an optimal balance between legal flexibility and legal certainty, which represents an avenue for further research and policy development beyond the jurisdictions analysed.
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15.
  • Fronzek, Stefan, et al. (författare)
  • Classifying multi-model wheat yield impact response surfaces showing sensitivity to temperature and precipitation change
  • 2018
  • Ingår i: Agricultural Systems. - : Elsevier BV. - 0308-521X. ; 159, s. 209-224
  • Tidskriftsartikel (refereegranskat)abstract
    • Crop growth simulation models can differ greatly in their treatment of key processes and hence in their response to environmental conditions. Here, we used an ensemble of 26 process-based wheat models applied at sites across a European transect to compare their sensitivity to changes in temperature (-2 to +9°C) and precipitation (-50 to +50%). Model results were analysed by plotting them as impact response surfaces (IRSs), classifying the IRS patterns of individual model simulations, describing these classes and analysing factors that may explain the major differences in model responses.The model ensemble was used to simulate yields of winter and spring wheat at four sites in Finland, Germany and Spain. Results were plotted as IRSs that show changes in yields relative to the baseline with respect to temperature and precipitation. IRSs of 30-year means and selected extreme years were classified using two approaches describing their pattern.The expert diagnostic approach (EDA) combines two aspects of IRS patterns: location of the maximum yield (nine classes) and strength of the yield response with respect to climate (four classes), resulting in a total of 36 combined classes defined using criteria pre-specified by experts. The statistical diagnostic approach (SDA) groups IRSs by comparing their pattern and magnitude, without attempting to interpret these features. It applies a hierarchical clustering method, grouping response patterns using a distance metric that combines the spatial correlation and Euclidian distance between IRS pairs. The two approaches were used to investigate whether different patterns of yield response could be related to different properties of the crop models, specifically their genealogy, calibration and process description.Although no single model property across a large model ensemble was found to explain the integrated yield response to temperature and precipitation perturbations, the application of the EDA and SDA approaches revealed their capability to distinguish: (i) stronger yield responses to precipitation for winter wheat than spring wheat; (ii) differing strengths of response to climate changes for years with anomalous weather conditions compared to period-average conditions; (iii) the influence of site conditions on yield patterns; (iv) similarities in IRS patterns among models with related genealogy; (v) similarities in IRS patterns for models with simpler process descriptions of root growth and water uptake compared to those with more complex descriptions; and (vi) a closer correspondence of IRS patterns in models using partitioning schemes to represent yield formation than in those using a harvest index.Such results can inform future crop modelling studies that seek to exploit the diversity of multi-model ensembles, by distinguishing ensemble members that span a wide range of responses as well as those that display implausible behaviour or strong mutual similarities.
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16.
  • Gardiner, Chris, et al. (författare)
  • Extracellular vesicles, tissue factor, cancer and thrombosis - discussion themes of the ISEV 2014 Educational Day.
  • 2015
  • Ingår i: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 4:1
  • Forskningsöversikt (refereegranskat)abstract
    • Although the association between cancer and venous thromboembolism (VTE) has long been known, the mechanisms are poorly understood. Circulating tissue factor-bearing extracellular vesicles have been proposed as a possible explanation for the increased risk of VTE observed in some types of cancer. The International Society for Extracellular Vesicles (ISEV) and International Society on Thrombosis and Haemostasis (ISTH) held a joint Educational Day in April 2014 to discuss the latest developments in this field. This review discusses the themes of that event and the ISEV 2014 meeting that followed.
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17.
  • Heaney, Liam G., et al. (författare)
  • Eosinophilic and Noneosinophilic Asthma : An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort
  • 2021
  • Ingår i: Chest. - : Elsevier BV. - 0012-3692. ; 160:3, s. 814-830
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. Research Question: What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? Study Design and Methods: This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). Results: One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV1, 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy. Interpretation: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.
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18.
  • Itzhaki, Ruth F., et al. (författare)
  • Microbes and Alzheimer's Disease
  • 2016
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 51:4, s. 979-984
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • We are researchers and clinicians working on Alzheimer’s disease (AD) or related topics, and we write to express our concern that one particular aspect of the disease has been neglected, even though treatment based on it might slow or arrest AD progression. We refer to the many studies, mainly on humans, implicating specific microbes in the elderly brain, notably herpes simplex virus type 1 (HSV1), Chlamydia pneumoniae, and several types of spirochaete, in the etiology of AD [1–4]. Fungal infection of AD brain [5, 6] has also been described, as well as abnormal microbiota in AD patient blood [7]. The first observations of HSV1 in AD brain were reported almost three decades ago [8]. The ever-increasing number of these studies (now about 100 on HSV1 alone) warrants re-evaluation of the infection and AD concept.AD is associated with neuronal loss and progressive synaptic dysfunction, accompanied by the deposition of amyloid-β (Aβ) peptide, a cleavage product of the amyloid-β protein precursor (AβPP), and abnormal forms of tau protein, markers that have been used as diagnostic criteria for the disease [9, 10]. These constitute the hallmarks of AD, but whether they are causes of AD or consequences is unknown. We suggest that these are indicators of an infectious etiology. In the case of AD, it is often not realized that microbes can cause chronic as well as acute diseases; that some microbes can remain latent in the body with the potential for reactivation, the effects of which might occur years after initial infection; and that people can be infected but not necessarily affected, such that ‘controls’, even if infected, are asymptomatic
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19.
  • Itzhaki, Ruth F., et al. (författare)
  • Microbes and Alzheimer's disease
  • 2017
  • Ingår i: Handbook of infection and Alzheimer's disease. - : IOS Press. - 9781614997054 - 9781614997061 ; , s. 3-8
  • Bokkapitel (refereegranskat)
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20.
  • Jin, Shoko, et al. (författare)
  • The wide-field, multiplexed, spectroscopic facility WEAVE : Survey design, overview, and simulated implementation
  • 2024
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 530:3, s. 2688-2730
  • Tidskriftsartikel (refereegranskat)abstract
    • WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, saw first light in late 2022. WEAVE comprises a new 2-deg field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366-959nm at R similar to 5000, or two shorter ranges at . After summarizing the design and implementation of WEAVE and its data systems, we present the organization, science drivers, and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for similar to 3 million stars and detailed abundances for similar to 1.5 million brighter field and open-cluster stars; (ii) survey similar to 0.4 million Galactic-plane OBA stars, young stellar objects, and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey similar to 400 neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionized gas in z < 0.5 cluster galaxies; (vi) survey stellar populations and kinematics in field galaxies at 0.3 less than or similar to z less than or similar to 0.7; (vii) study the cosmic evolution of accretion and star formation using >1 million spectra of LOFAR-selected radio sources; and (viii) trace structures using intergalactic/circumgalactic gas at z > 2. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator.
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