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- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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- Harrison, J.R., et al.
(author)
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Overview of new MAST physics in anticipation of first results from MAST Upgrade
- 2019
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Research review (peer-reviewed)abstract
- The mega amp spherical tokamak (MAST) was a low aspect ratio device (R/a = 0.85/0.65 ∼ 1.3) with similar poloidal cross-section to other medium-size tokamaks. The physics programme concentrates on addressing key physics issues for the operation of ITER, design of DEMO and future spherical tokamaks by utilising high resolution diagnostic measurements closely coupled with theory and modelling to significantly advance our understanding. An empirical scaling of the energy confinement time that favours higher power, lower collisionality devices is consistent with gyrokinetic modelling of electron scale turbulence. Measurements of ion scale turbulence with beam emission spectroscopy and gyrokinetic modelling in up-down symmetric plasmas find that the symmetry of the turbulence is broken by flow shear. Near the non-linear stability threshold, flow shear tilts the density fluctuation correlation function and skews the fluctuation amplitude distribution. Results from fast particle physics studies include the observation that sawteeth are found to redistribute passing and trapped fast particles injected from neutral beam injectors in equal measure, suggesting that resonances between the m = 1 perturbation and the fast ion orbits may be playing a dominant role in the fast ion transport. Measured D-D fusion products from a neutron camera and a charged fusion product detector are 40% lower than predictions from TRANSP/NUBEAM, highlighting possible deficiencies in the guiding centre approximation. Modelling of fast ion losses in the presence of resonant magnetic perturbations (RMPs) can reproduce trends observed in experiments when the plasma response and charge-exchange losses are accounted for. Measurements with a neutral particle analyser during merging-compression start-up indicate the acceleration of ions and electrons. Transport at the plasma edge has been improved through reciprocating probe measurements that have characterised a geodesic acoustic mode at the edge of an ohmic L-mode plasma and particle-in-cell modelling has improved the interpretation of plasma potential estimates from ball-pen probes. The application of RMPs leads to a reduction in particle confinement in L-mode and H-mode and an increase in the core ionization source. The ejection of secondary filaments following type-I ELMs correlates with interactions with surfaces near the X-point. Simulations of the interaction between pairs of filaments in the scrape-off layer suggest this results in modest changes to their velocity, and in most cases can be treated as moving independently. A stochastic model of scrape-off layer profile formation based on the superposition of non-interacting filaments is in good agreement with measured time-average profiles. Transport in the divertor has been improved through fast camera imaging, indicating the presence of a quiescent region devoid of filament near the X-point, extending from the separatrix to ψ n ∼ 1.02. Simulations of turbulent transport in the divertor show that the angle between the divertor leg on the curvature vector strongly influences transport into the private flux region via the interchange mechanism. Coherence imaging measurements show counter-streaming flows of impurities due to gas puffing increasing the pressure on field lines where the gas is ionised. MAST Upgrade is based on the original MAST device, with substantially improved capabilities to operate with a Super-X divertor to test extended divertor leg concepts. SOLPS-ITER modelling predicts the detachment threshold will be reduced by more than a factor of 2, in terms of upstream density, in the Super-X compared with a conventional configuration and that the radiation front movement is passively stabilised before it reaches the X-point. 1D fluid modelling reveals the key role of momentum and power loss mechanisms in governing detachment onset and evolution. Analytic modelling indicates that long legs placed at large major radius, or equivalently low at the target compared with the X-point are more amenable to external control. With MAST Upgrade experiments expected in 2019, a thorough characterisation of the sources of the intrinsic error field has been carried out and a mitigation strategy developed.
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- Heap, Graham A., et al.
(author)
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HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants
- 2014
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:10, s. 1131-1134
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Journal article (peer-reviewed)abstract
- Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 x 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the H LA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.
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7. |
- Akkaya, Munir, et al.
(author)
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A single-nucleotide polymorphism in a Plasmodium berghei ApiAP2 transcription factor alters the development of host immunity
- 2020
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In: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 6:6
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Journal article (peer-reviewed)abstract
- The acquisition of malaria immunity is both remarkably slow and unpredictable. At present, we know little about the malaria parasite genes that influence the host's ability to mount a protective immune response. Here, we show that a single-nucleotide polymorphism (SNP) resulting in a single amino acid change (S to F) in an ApiAP2 transcription factor in the rodent malaria parasite Plasmodium berghei (Pb) NK65 allowed infected mice to mount a T helper cell 1 (T(H)1)-type immune response that controlled subsequent infections. As compared to PbNK65(S), PbNK65(F) parasites differentially expressed 46 genes, most of which are predicted to play roles in immune evasion. PbNK65(F) infections resulted in an early interferon-gamma response and a later expansion of germinal centers, resulting in high levels of infected red blood cell-specific T(H)1-type immunoglobulin G2b (IgG2b) and IgG2c antibodies. Thus, the Pb ApiAP2 transcription factor functions as a critical parasite virulence factor in malaria infections.
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8. |
- Greco, R, et al.
(author)
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Hematopoietic stem cell transplantation for autoimmune diseases in the time of COVID-19: EBMT guidelines and recommendations
- 2021
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In: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 56:7, s. 1493-1508
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Journal article (peer-reviewed)abstract
- Coronavirus disease-19 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), represents one of the biggest challenges of 21st century, threatening public health around the globe. Increasing age and presence of co-morbidities are reported risk factors for severe disease and mortality, along with autoimmune diseases (ADs) and immunosuppressive treatments such as haematopoietic stem cell transplantation (HSCT), which are also associated with adverse outcomes. We review the impact of the pandemic on specific groups of patients with neurological, rheumatological, and gastroenterological indications, along with the challenges delivering HSCT in adult and pediatric populations. Moving forward, we developed consensus-based guidelines and recommendations for best practice and quality of patient care in order to support clinicians, scientists, and their multidisciplinary teams, as well as patients and their carers. These guidelines aim to support national and international organizations related to autoimmune diseases and local clinical teams delivering HSCT. Areas of unmet need and future research questions are also highlighted. The waves of the COVID-19 pandemic are predicted to be followed by an “endemic” phase and therefore an ongoing risk within a “new normality”. These recommendations reflect currently available evidence, coupled with expert opinion, and will be revised according to necessary modifications in practice.
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9. |
- Levitis, E, et al.
(author)
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Centering inclusivity in the design of online conferences-An OHBM-Open Science perspective
- 2021
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In: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 10:8
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Journal article (peer-reviewed)abstract
- As the global health crisis unfolded, many academic conferences moved online in 2020. This move has been hailed as a positive step towards inclusivity in its attenuation of economic, physical, and legal barriers and effectively enabled many individuals from groups that have traditionally been underrepresented to join and participate. A number of studies have outlined how moving online made it possible to gather a more global community and has increased opportunities for individuals with various constraints, e.g., caregiving responsibilities.Yet, the mere existence of online conferences is no guarantee that everyone can attend and participate meaningfully. In fact, many elements of an online conference are still significant barriers to truly diverse participation: the tools used can be inaccessible for some individuals; the scheduling choices can favour some geographical locations; the set-up of the conference can provide more visibility to well-established researchers and reduce opportunities for early-career researchers. While acknowledging the benefits of an online setting, especially for individuals who have traditionally been underrepresented or excluded, we recognize that fostering social justice requires inclusivity to actively be centered in every aspect of online conference design.Here, we draw from the literature and from our own experiences to identify practices that purposefully encourage a diverse community to attend, participate in, and lead online conferences. Reflecting on how to design more inclusive online events is especially important as multiple scientific organizations have announced that they will continue offering an online version of their event when in-person conferences can resume.
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10. |
- Ardo, Shane, et al.
(author)
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Pathways to electrochemical solar-hydrogen technologies
- 2018
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In: Energy & Environmental Science. - : Royal Society of Chemistry. - 1754-5692 .- 1754-5706. ; 11:10, s. 2768-2783
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Research review (peer-reviewed)abstract
- Solar-powered electrochemical production of hydrogen through water electrolysis is an active and important research endeavor. However, technologies and roadmaps for implementation of this process do not exist. In this perspective paper, we describe potential pathways for solar-hydrogen technologies into the marketplace in the form of photoelectrochemical or photovoltaic-driven electrolysis devices and systems. We detail technical approaches for device and system architectures, economic drivers, societal perceptions, political impacts, technological challenges, and research opportunities. Implementation scenarios are broken down into short-term and long-term markets, and a specific technology roadmap is defined. In the short term, the only plausible economical option will be photovoltaic-driven electrolysis systems for niche applications. In the long term, electrochemical solar-hydrogen technologies could be deployed more broadly in energy markets but will require advances in the technology, significant cost reductions, and/ or policy changes. Ultimately, a transition to a society that significantly relies on solar-hydrogen technologies will benefit from continued creativity and influence from the scientific community.
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11. |
- Brandes, Axel, et al.
(author)
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Consumer-Led Screening for Atrial Fibrillation : Frontier Review of the AF-SCREEN International Collaboration
- 2022
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In: Circulation. - 0009-7322 .- 1524-4539. ; 146:19, s. 1461-1474
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Research review (peer-reviewed)abstract
- The technological evolution and widespread availability of wearables and handheld ECG devices capable of screening for atrial fibrillation (AF), and their promotion directly to consumers, has focused attention of health care professionals and patient organizations on consumer-led AF screening. In this Frontiers review, members of the AF-SCREEN International Collaboration provide a critical appraisal of this rapidly evolving field to increase awareness of the complexities and uncertainties surrounding consumer-led AF screening. Although there are numerous commercially available devices directly marketed to consumers for AF monitoring and identification of unrecognized AF, health care professional-led randomized controlled studies using multiple ECG recordings or continuous ECG monitoring to detect AF have failed to demonstrate a significant reduction in stroke. Although it remains uncertain if consumer-led AF screening reduces stroke, it could increase early diagnosis of AF and facilitate an integrated approach, including appropriate anticoagulation, rate or rhythm management, and risk factor modification to reduce complications. Companies marketing AF screening devices should report the accuracy and performance of their products in high- and low-risk populations and avoid claims about clinical outcomes unless improvement is demonstrated in randomized clinical trials. Generally, the diagnostic yield of AF screening increases with the number, duration, and temporal dispersion of screening sessions, but the prognostic importance may be less than for AF detected by single-time point screening, which is largely permanent, persistent, or high-burden paroxysmal AF. Consumer-initiated ECG recordings suggesting possible AF always require confirmation by a health care professional experienced in ECG reading, whereas suspicion of AF on the basis of photoplethysmography must be confirmed with an ECG. Consumer-led AF screening is unlikely to be cost-effective for stroke prevention in the predominantly young, early adopters of this technology. Studies in older people at higher stroke risk are required to demonstrate both effectiveness and cost-effectiveness. The direct interaction between companies and consumers creates new regulatory gaps in relation to data privacy and the registration of consumer apps and devices. Although several barriers for optimal use of consumer-led screening exist, results of large, ongoing trials, powered to detect clinical outcomes, are required before health care professionals should support widespread adoption of consumer-led AF screening.
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12. |
- Eapen, Mary, et al.
(author)
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Long-Term Survival and Late Deaths after Hematopoietic Cell Transplantation for Primary Immunodeficiency Diseases and Inborn Errors of Metabolism.
- 2012
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In: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. - 1523-6536. ; 18:9, s. 1438-1445
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Journal article (peer-reviewed)abstract
- It is uncertain whether late mortality rates after hematopoietic cell transplantation for severe combined immunodeficiency (SCID), non-SCID primary immunodeficiency diseases (non-SCID PIDD), and inborn errors of metabolism (IEM) return to rates observed in the general population, matched for age, sex, and nationality. We studied patients with SCID (n = 201), non-SCID PIDD (n = 405), and IEM (n = 348) who survived for at least 2 years after transplantation with normal T cell function (SCID) or >95% donor chimerism (non-SCID PIDD and IEM). Importantly, mortality rate was significantly higher in these patients compared with the general population for several years after transplantation. The rate decreased toward the normal rate in patients with SCID and non-SCID PIDD beyond 6 years after transplantation, but not in patients with IEM. Active chronic graft-versus-host disease at 2 years was associated with increased risk of late mortality for all diseases (hazard ratio [HR], 1.87; P = .05). In addition, late mortality was higher in patients with non-SCID PIDD who received T cell-depleted grafts (HR 4.16; P = .007) and in patients with IEM who received unrelated donor grafts (HR, 2.72; P = .03) or mismatched related donor grafts (HR, 3.76; P = .01). The finding of higher mortality rates in these long-term survivors for many years after transplantation confirms the need for long-term surveillance.
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13. |
- Freedman, Ben, et al.
(author)
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Screening for Atrial Fibrillation A Report of the AF-SCREEN International Collaboration
- 2017
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In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 135:19, s. 1851-
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Journal article (peer-reviewed)abstract
- Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country-and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.
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14. |
- Gero, D., et al.
(author)
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Defining Global Benchmarks in Bariatric Surgery A Retrospective Multicenter Analysis of Minimally Invasive Roux-en-Y Gastric Bypass and Sleeve Gastrectomy
- 2019
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In: Annals of Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 0003-4932 .- 1528-1140. ; 270:5, s. 859-867
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Journal article (peer-reviewed)abstract
- Objective: To define "best possible'' outcomes for bariatric surgery (BS)(Roux-en-Y gastric bypass [RYGB] and sleeve gastrectomy [SG]). Background: Reference values for optimal surgical outcomes in welldefined low-risk bariatric patients have not been established so far. Consequently, outcome comparison across centers and over time is impeded by heterogeneity in case-mix. Methods: Out of 39,424 elective BS performed in 19 high-volume academic centers from 3 continents between June 2012 and May 2017, we identified 4120 RYGB and 1457 SG low-risk cases defined by absence of previous abdominal surgery, concomitant procedures, diabetes mellitus, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, anticoagulation, BMI>50 kg/m(2) and age>65 years. We chose clinically relevant endpoints covering the intra- and postoperative course. Complications were graded by severity using the comprehensive complication index. Benchmark values were defined as the 75th percentile of the participating centers' median values for respective quality indicators. Results: Patients were mainly females (78%), aged 38+/-11 years, with a baseline BMI 40.8 +/- 5.8 kg/m(2). Over 90 days, 7.2% of RYGB and 6.2% of SG patients presented at least 1 complication and no patients died (mortality in nonbenchmark cases: 0.06%). The most frequent reasons for readmission after 90-days following both procedures were symptomatic cholelithiasis and abdominal pain of unknown origin. Benchmark values for both RYGB and SG at 90-days postoperatively were 5.5% Clavien-Dindo grade >= IIIa complication rate, 5.5% readmission rate, and comprehensive complication index <= 33.73 in the subgroup of patients presenting at least 1 grade >= II complication. Conclusion: Benchmark cutoffs targeting perioperative outcomes in BS offer a new tool in surgical quality-metrics and may be implemented in qualityimprovement cycle. ClinicalTrials.gov Identifier NCT03440138
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- Ljungman, P, et al.
(author)
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COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey
- 2021
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In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35:10, s. 2885-2894
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Journal article (peer-reviewed)abstract
- This study reports on 382 COVID-19 patients having undergone allogeneic (n = 236) or autologous (n = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0–80.3) for allogeneic, and 60.6 years (7.7–81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2–292.7) in allogeneic and 24.6 months (−0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p = 0.02), need for ICU (p < 0.0001) and moderate/high immunodeficiency index (p = 0.04) increased the risk while better performance status (p = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19.
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18. |
- Mueller-Wohlfahrt, H. W., et al.
(author)
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Terminology and classification of muscle injuries in sport: The Munich consensus statement
- 2013
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In: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 47:6
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Journal article (peer-reviewed)abstract
- Objective To provide a clear terminology and classification of muscle injuries in order to facilitate Methods Thirty native English-speaking scientists and team doctors of national and first division Results The response rate of the survey was 63%. The responses confirmed the marked variability in Conclusions A consistent English terminology as well as a comprehensive classification system for What are the new things Consensus definitions of the terminology which is used in the field of muscle
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- Saccardi, R, et al.
(author)
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Benchmarking of survival outcomes following Haematopoietic Stem Cell Transplantation (HSCT): an update of the ongoing project of the European Society for Blood and Marrow Transplantation (EBMT) and Joint Accreditation Committee of ISCT and EBMT (JACIE)
- 2023
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In: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 58:6, s. 659-666
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Journal article (peer-reviewed)abstract
- From 2016 EBMT and JACIE developed an international risk-adapted benchmarking program of haematopoietic stem cell transplant (HSCT) outcome to provide individual EBMT Centers with a means of quality-assuring the HSCT process and meeting FACT-JACIE accreditation requirements relating to 1-year survival outcomes. Informed by previous experience from Europe, North America and Australasia, the Clinical Outcomes Group (COG) established criteria for patient and Center selection, and a set of key clinical variables within a dedicated statistical model adapted to the capabilities of the EBMT Registry. The first phase of the project was launched in 2019 to test the acceptability of the benchmarking model through assessment of Centers’ performance for 1-year data completeness and survival outcomes of autologous and allogeneic HSCT covering 2013–2016. A second phase was delivered in July 2021 covering 2015–2019 and including survival outcomes. Reports of individual Center performance were shared directly with local principal investigators and their responses were assimilated. The experience thus far has supported the feasibility, acceptability and reliability of the system as well as identifying its limitations. We provide a summary of experience and learning so far in this ‘work in progress’, as well as highlighting future challenges of delivering a modern, robust, data-complete, risk-adapted benchmarking program across new EBMT Registry systems.
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21. |
- Snowden, JA, et al.
(author)
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Benchmarking of survival outcomes following haematopoietic stem cell transplantation: A review of existing processes and the introduction of an international system from the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE)
- 2020
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In: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 55:4, s. 681-694
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Journal article (peer-reviewed)abstract
- In many healthcare settings, benchmarking for complex procedures has become a mandatory requirement by competent authorities, regulators, payers and patients to assure clinical performance, cost-effectiveness and safe care of patients. In several countries inside and outside Europe, benchmarking systems have been established for haematopoietic stem cell transplantation (HSCT), but access is not universal. As benchmarking is now integrated into the FACT-JACIE standards, the EBMT and JACIE established a Clinical Outcomes Group (COG) to develop and introduce a universal system accessible across EBMT members. Established systems from seven European countries (United Kingdom, Italy, Belgium, France, Germany, Spain, Switzerland), USA and Australia were appraised, revealing similarities in process, but wide variations in selection criteria and statistical methods. In tandem, the COG developed the first phase of a bespoke risk-adapted international benchmarking model for one-year survival following allogeneic and autologous HSCT based on current capabilities within the EBMT registry core dataset. Data completeness, which has a critical impact on validity of centre comparisons, is also assessed. Ongoing development will include further scientific validation of the model, incorporation of further variables (when appropriate) alongside implementation of systems for clinically meaningful interpretation and governance aiming to maximise acceptance to centres, clinicians, payers and patients across EBMT.
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24. |
- Viñuela, Ana, et al.
(author)
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Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4912-4912
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Journal article (peer-reviewed)abstract
- Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, key tissues and cell-types required for functional inference are absent from large-scale resources. Here we explore the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using data from 420 donors. We find: (a) 7741 cis-eQTLs in islets with a replication rate across 44 GTEx tissues between 40% and 73%; (b) marked overlap between islet cis-eQTL signals and active regulatory sequences in islets, with reduced eQTL effect size observed in the stretch enhancers most strongly implicated in GWAS signal location; (c) enrichment of islet cis-eQTL signals with T2D risk variants identified in genome-wide association studies; and (d) colocalization between 47 islet cis-eQTLs and variants influencing T2D or glycemic traits, including DGKB and TCF7L2. Our findings illustrate the advantages of performing functional and regulatory studies in disease relevant tissues.
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