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- Fenstermacher, M.E., et al.
(author)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Journal article (peer-reviewed)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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- Kattge, Jens, et al.
(author)
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TRY plant trait database - enhanced coverage and open access
- 2020
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In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Journal article (peer-reviewed)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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- Polme, S., et al.
(author)
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FungalTraits: a user-friendly traits database of fungi and fungus-like stramenopiles
- 2020
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In: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 105:1, s. 1-16
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Journal article (peer-reviewed)abstract
- The cryptic lifestyle of most fungi necessitates molecular identification of the guild in environmental studies. Over the past decades, rapid development and affordability of molecular tools have tremendously improved insights of the fungal diversity in all ecosystems and habitats. Yet, in spite of the progress of molecular methods, knowledge about functional properties of the fungal taxa is vague and interpretation of environmental studies in an ecologically meaningful manner remains challenging. In order to facilitate functional assignments and ecological interpretation of environmental studies we introduce a user friendly traits and character database FungalTraits operating at genus and species hypothesis levels. Combining the information from previous efforts such as FUNGuild and Fun(Fun) together with involvement of expert knowledge, we reannotated 10,210 and 151 fungal and Stramenopila genera, respectively. This resulted in a stand-alone spreadsheet dataset covering 17 lifestyle related traits of fungal and Stramenopila genera, designed for rapid functional assignments of environmental studies. In order to assign the trait states to fungal species hypotheses, the scientific community of experts manually categorised and assigned available trait information to 697,413 fungal ITS sequences. On the basis of those sequences we were able to summarise trait and host information into 92,623 fungal species hypotheses at 1% dissimilarity threshold.
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| 8. |
- Bethlehem, RAI, et al.
(author)
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Brain charts for the human lifespan
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 604:79057906, s. 525-
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Journal article (peer-reviewed)abstract
- Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
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- Duffy, J. M. N., et al.
(author)
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Top 10 priorities for future infertility research: an international consensus development study
- 2020
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In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 35:12, s. 2715-2724
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Journal article (peer-reviewed)abstract
- STUDY QUESTION: Can the priorities for future research in infertility be identified? SUMMARY ANSWER: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care for people with fertility problems were identified. WHAT IS KNOWN ALREADY: Many fundamental questions regarding the prevention, management and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. STUDY DESIGN, SIZE, DURATION: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, people with fertility problems and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. MAIN RESULTS AND THE ROLE OF CHANCE: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties was entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI and IVF) and ethics, access and organization of care were identified during a consensus development meeting involving 41 participants from I I countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research and population science. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgment and arbitrary consensus definitions. WIDER IMPLICATIONS OF THE FINDINGS: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems and others, will help research funding organizations and researchers to develop their future research agenda.
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| 12. |
- Tedersoo, L., et al.
(author)
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The Global Soil Mycobiome consortium dataset for boosting fungal diversity research
- 2021
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In: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 111, s. 573-588
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Journal article (peer-reviewed)abstract
- Fungi are highly important biotic components of terrestrial ecosystems, but we still have a very limited understanding about their diversity and distribution. This data article releases a global soil fungal dataset of the Global Soil Mycobiome consortium (GSMc) to boost further research in fungal diversity, biogeography and macroecology. The dataset comprises 722,682 fungal operational taxonomic units (OTUs) derived from PacBio sequencing of full-length ITS and 18S-V9 variable regions from 3200 plots in 108 countries on all continents. The plots are supplied with geographical and edaphic metadata. The OTUs are taxonomically and functionally assigned to guilds and other functional groups. The entire dataset has been corrected by excluding chimeras, index-switch artefacts and potential contamination. The dataset is more inclusive in terms of geographical breadth and phylogenetic diversity of fungi than previously published data. The GSMc dataset is available over the PlutoF repository.
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- Bayley, PJ, et al.
(author)
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2013 SYR Accepted Poster Abstracts
- 2013
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In: International journal of yoga therapy. - 1531-2054. ; 23:1, s. 32-53
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Journal article (peer-reviewed)
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| 15. |
- Benza, Raymond L., et al.
(author)
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CS1, a controlled-release formulation of valproic acid, for the treatment of patients with pulmonary arterial hypertension: Rationale and design of a Phase 2 clinical trial
- 2024
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In: PULMONARY CIRCULATION. - 2045-8932 .- 2045-8940. ; 14:1
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Journal article (peer-reviewed)abstract
- Although rare, pulmonary arterial hypertension (PAH) is associated with substantial morbidity and a median survival of approximately 7 years, even with treatment. Current medical therapies have a primarily vasodilatory effect and do not modify the underlying pathology of the disease. CS1 is a novel oral, controlled-release formulation of valproic acid, which exhibits a multi-targeted mode of action (pulmonary pressure reduction, reversal of vascular remodeling, anti-inflammatory, anti-fibrotic, and anti-thrombotic) and therefore potential for disease modification and right ventricular modeling in patients with PAH. A Phase 1 study conducted in healthy volunteers indicated favorable safety and tolerability, with no increased risk of bleeding and significant reduction of plasminogen activator inhibitor 1. In an ongoing randomized Phase 2 clinical trial, three doses of open-label CS1 administered for 12 weeks is evaluating the use of multiple outcome measures. The primary endpoint is safety and tolerability, as measured by the occurrence of adverse events. Secondary outcome measures include the use of the CardioMEMS (TM) HF System, which provides a noninvasive method of monitoring pulmonary artery pressure, as well as cardiac magnetic resonance imaging and echocardiography. Other outcomes include changes in risk stratification (using the REVEAL 2.0 and REVEAL Lite 2 tools), patient reported outcomes, functional capacity, 6-min walk distance, actigraphy, and biomarkers. The pharmacokinetic profile of CS1 will also be evaluated. Overall, the novel design and unique, extensive clinical phenotyping of participants in this trial will provide ample evidence to inform the design of any future Phase 3 studies with CS1.
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- Fujimoto-Adamson, Naoki, et al.
(author)
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Exploring the supervisors’ writing experiences and their effects on undergraduate thesis supervisory practices : A comparison of Japanese and Swedish contexts
- 2024
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In: Research in Comparative and International Education. - : Sage Publications. - 1745-4999. ; 19:1, s. 23-45
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Journal article (peer-reviewed)abstract
- This study explored the effects of the writing experiences of supervisors on undergraduate English language thesis supervision, specifically focusing on the Japanese and Swedish tertiary contexts where English medium instruction (EMI) is delivered to students whose first language is not English. Employing a Collaborative Autoethnographic (CAE) approach, three teacher-researchers working at universities in Japan and Sweden jointly co-constructed their narratives about their own literacy practices in the historical development of their writing and current thesis supervision. Findings demonstrated limited influences of the teachers’ personal experiences on their practices, with social and educational norms in each country emerging as more significant factors. Particularly, the teacher-centeredness and exam-orientation were observed by the Japan-based supervisors to affect Japanese students, whereas the more horizontal relationship between students and teachers in Swedish education was reported as impacting university students’ autonomy in thesis writing. We concluded that in both tertiary EMI contexts, local embedded educational norms largely influenced teachers' supervisory practices.
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- Adamson, L, et al.
(author)
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Insulin and IGF-1 mediated inhibition of apoptosis in CHO cells grown in suspension in a protein-free medium
- 2007
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In: Alternatives to laboratory animals : ATLA. - : SAGE Publications. - 0261-1929 .- 2632-3559. ; 35:3, s. 349-352
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Journal article (peer-reviewed)abstract
- When Chinese hamster ovary (CHO) cells were grown in suspension and deprived of serum, 40% of them became apoptotic after 72 hours, as determined by flow cytometry analysis of TUNEL-labelled cells. Cell viability, assessed by erythrocin B staining, decreased correspondingly. An increase in the total fraction of cells expressing interleukin converting enzyme (ICE; caspase 1), B-cell lymphoma 2 protein (Bcl-2,) and Bcl-2 associated x protein (Bax) was shown by antibody probing and subsequent flow cytometry. The p53 tumour suppressor gene product level remained low within the cell population. Insulin-like growth factor-1 (IGF-1) inhibited cell death in a concentration-dependent manner, and at 20ng/ml, cell viability was maintained close to 100% and no apoptotic cells were detected. Also, insulin was shown to inhibit cell death — at 1.0μg/ml, cell viability was 95%, whereas 10% of the cells stained for apoptosis. At the highest concentrations of IGF-1 and insulin, the expression of ICE, Bcl-2 and Bax was fully suppressed, whereas the p53 product level increased, despite still being detectable in a minority of cells. Under these conditions, IGF-1 may increase p53 expression to restrain abnormal cell proliferation. It is concluded that special attention should be paid to exposure and culture conditions that induce acquired susceptibility to a toxic insult, during the development and validation of cell-based assays.
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- Anderbro, Therese, et al.
(author)
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A longitudinal study of fear of hypoglycemia in type 1 diabetes
- 2015
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Conference paper (peer-reviewed)abstract
- AimThe aim of this study was to investigate fear of hypoglycemia (FoH) longitudinally in adult patients with type 1 diabetes. Specifically, we investigated two subgroups of patients who over four years either showed a significantly higher or significantly lower level of FoH in order to identify factors associated with changes in FoH.MethodThe Swedish version of the Hypoglycemia Fear Survey (HFS) along with a questionnaire to assess hypoglycemia history (mild, moderate, nocturnal and severe hypoglycaemia (SH), unawareness, and daytime/nocturnal self-monitoring of blood glucose (SMBG)) were sent by mail to 764 patients in 2010. The responders in 2010 (n=469) received another set of the same two questionnaires in 2014. A1c, insulin regimen, weight and creatinine from 2010 and 2014 were obtained from medical records. Those with an absolute difference in HFS scores ≥ 75th percentile were included in the subgroup analyses. Statistical analyses included one-sample t-tests and chi-square.ResultsThe absolute difference in the HFS total score (n=359) between 2010 and 2014 was m=±7.6, SD ±6 (range -29 - +35). In the subgroup with increased FoH 2014 (n=45), more patients reported unawareness (76% vs 58%, Χ2= 5.05, p= 0.025) and a higher frequency of moderate hypoglycemia (52% v s 38%, Χ2= 3.93, p= 0.047) compared to 2010. In the group with decreased FoH (n=43), fewer patients reported going to the emergency department due to hypoglycemia in 2014 compared to 2010 (2% vs 14%, Χ2= 4.84, p= 0.028). There were no differences in the remaining hypoglycemia history variables or medical variables between 2010 and 2014. Between group analyzes show that in the decreased FoH group more patients have a high frequency of daily SMBG compared to the increased FoH group in 2010 (35% vs 17%, Χ2= 12.23, p= 0.00) and in 2014 (33% vs 13%, Χ2= 13.75, p= 0.00). In the increased FoH group more patients report a high level of mild (67% vs 49%,Χ2= 6.4, p= 0.011) and moderate (52% vs 23%,Χ2= 14.00, p= 0.00) hypoglycemic episodes as well as unawareness (76% vs 54%,Χ2= 11.37, p= 0.001) in 2014 compared with the decreased FoH group.DiscussionTo our knowledge, this is the first longitudinal study of FoH in patients with type 1 diabetes. Our study shows that FoH is stable across time for most patients although a number of patients show increased or decreased levels of FoH. The patients whose level of FoH increased experienced a higher frequency of moderate hypoglycemic episodes and more hypoglycemic unawareness in 2014.
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- Curtain, J. P., et al.
(author)
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Prevalent and Incident Anemia in PARADIGM-HF and the Effect of Sacubitril/Valsartan
- 2023
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In: Jacc-Heart Failure. - 2213-1779. ; 11:7, s. 749-759
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Journal article (peer-reviewed)abstract
- BACKGROUND Anemia is common in patients with heart failure with reduced ejection fraction and is associated with poor clinical outcomes. Renin-angiotensin system blockers lower hemoglobin and may induce anemia. OBJECTIVES The authors investigated whether concomitant neprilysin inhibition might ameliorate this effect of renin-angiotensin system blockers in PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure). METHODS Anemia was defined as hemoglobin <120 g/L in women and <130 g/L in men at screening. The authors investigated the effect of randomized treatment on clinical outcomes according to anemia status, change in hemoglobin from baseline, and the incidence of anemia. RESULTS Of 8,239 participants with a baseline hemoglobin measurement, 1,677 (20.4%) were anemic. Patients with anemia had a more severe heart failure profile, worse kidney function, greater neurohormonal derangement, and worse clinical outcomes. Sacubitril/valsartan, compared with enalapril, decreased the risk of cardiovascular death or heart failure hospitalization similarly in patients with (HR: 0.84; 95% CI: 0.71-1.00) and without anemia (HR: 0.78 [95% CI: 0.71-0.87]; P value for interaction 1/4 0.478). Between baseline and 12 months, hemoglobin decreased by 1.5 g/L (95% CI: 1.2-1.7 g/L) with sacubitril/valsartan compared with 2.3 g/L (95% CI: 2.0-2.6 g/L) with enalapril: mean difference 0.8 g/L (95% CI: 0.5-1.2 g/L; P < 0.001). Patients assigned to sacubitril/valsartan were less likely to develop anemia at 12 months (321 of 2,806 [11.4%]) compared with patients randomized to enalapril (440 of 2,824 [15.6%]) (OR: 0.70 [95% CI: 0.60-0.81]; P < 0.001). These findings were similar in PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) (sacubitril/valsartan vs valsartan). There was biomarker evidence of increased iron utilization with sacubitril/valsartan. CONCLUSIONS Irrespective of anemia status, sacubitril/valsartan compared with enalapril, decreased mortality and hospitalization. Hemoglobin decreased less with sacubitril/valsartan and the incidence of new anemia was lower with sacubitril/valsartan.
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- Ferrer-Wreder, Laura, et al.
(author)
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Advancing Intervention Science Through Effectiveness Research : A Global Perspective
- 2012
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In: Child and Youth Care Forum. - : Springer Science+Business Media B.V.. - 1053-1890 .- 1573-3319. ; 41:2, s. 109-117
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Journal article (peer-reviewed)abstract
- Background: Effectiveness research is maturing as a field within intervention and prevention science. Effectiveness research involves the implementation and evaluation of the effectiveness of the dissemination of evidence-based interventions in everyday circumstances (i.e., type 2 translational research). Effectiveness research is characterized by diverse types of research studies. Progress in this field has the potential to inform several debates within intervention science [e.g., fidelity versus local and cultural adaptation; identification of core components, effective dissemination systems). Objective: To provide illustrations from different countries (Ireland, Italy, South Africa, Sweden, New Zealand, and the United States) of how intervention science might raise the value of future effectiveness or type 2 translational research. Methods: Themes raised by individual articles and across articles are summarized and expanded on in this commentary. Results: Themes consist of raising awareness about the importance of effectiveness research on the cultural adaptation of evidence-based interventions and intervention support structures, as well as further development of strategies to bridge the gap between research and practice. Conclusions: Effectiveness research has an important role to play in affecting systemic change on a population level and allowing us to gain a realistic global understanding of the phenomena we hope to change through interventions. Articles in this special issue provide reports from social scientists and practitioners located in various parts of the world and offer a rich, diverse portrait of effectiveness research and theory development. The totality of the work contained in this special issue anticipates many of the changes that intervention and prevention science will undergo as we progress and develop effective dissemination strategies for evidence-based interventions that promote positive youth development and prevent youth and family problems on a global scale.
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| 49. |
- Hardy, Victoria, et al.
(author)
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The added value of a mobile application of Community Case Management on referral, re-consultation and hospitalization rates of children aged under 5 years in two districts in Northern Malawi : study protocol for a pragmatic, stepped-wedge cluster-randomized controlled trial
- 2017
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In: Trials. - : BioMed Central. - 1745-6215. ; 18:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: There is evidence to suggest that frontline community health workers in Malawi are under-referring children to higher-level facilities. Integrating a digitized version of paper-based methods of Community Case Management (CCM) could strengthen delivery, increasing urgent referral rates and preventing unnecessary re-consultations and hospital admissions. This trial aims to evaluate the added value of the Supporting LIFE electronic Community Case Management Application (SL eCCM App) compared to paper-based CCM on urgent referral, re-consultation and hospitalization rates, in two districts in Northern Malawi.METHODS/DESIGN: This is a pragmatic, stepped-wedge cluster-randomized trial assessing the added value of the SL eCCM App on urgent referral, re-consultation and hospitalization rates of children aged 2 months and older to up to 5 years, within 7 days of the index visit. One hundred and two health surveillance assistants (HSAs) were stratified into six clusters based on geographical location, and clusters randomized to the timing of crossover to the intervention using simple, computer-generated randomization. Training workshops were conducted prior to the control (paper-CCM) and intervention (paper-CCM + SL eCCM App) in assigned clusters. Neither participants nor study personnel were blinded to allocation. Outcome measures were determined by abstraction of clinical data from patient records 2 weeks after recruitment. A nested qualitative study explored perceptions of adherence to urgent referral recommendations and a cost evaluation determined the financial and time-related costs to caregivers of subsequent health care utilization. The trial was conducted between July 2016 and February 2017.DISCUSSION: This is the first large-scale trial evaluating the value of adding a mobile application of CCM to the assessment of children aged under 5 years. The trial will generate evidence on the potential use of mobile health for CCM in Malawi, and more widely in other low- and middle-income countries.TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02763345 . Registered on 3 May 2016.
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