| 1. |
- Aad, G., et al.
(author)
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- 2012
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swepub:Mat__t (peer-reviewed)
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| 2. |
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- 2019
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Journal article (peer-reviewed)
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| 3. |
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| 4. |
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| 5. |
- Bar, N., et al.
(author)
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A reference map of potential determinants for the human serum metabolome
- 2020
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In: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Journal article (peer-reviewed)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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| 6. |
- Kueppers, Michael, et al.
(author)
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Triple F-a comet nucleus sample return mission
- 2009
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In: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 23:3, s. 809-847
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Journal article (peer-reviewed)abstract
- The Triple F (Fresh From the Fridge) mission, a Comet Nucleus Sample Return, has been proposed to ESA's Cosmic Vision program. A sample return from a comet enables us to reach the ultimate goal of cometary research. Since comets are the least processed bodies in the solar system, the proposal goes far beyond cometary science topics (like the explanation of cometary activity) and delivers invaluable information about the formation of the solar system and the interstellar molecular cloud from which it formed. The proposed mission would extract three sample cores of the upper 50 cm from three locations on a cometary nucleus and return them cooled to Earth for analysis in the laboratory. The simple mission concept with a touch-and-go sampling by a single spacecraft was proposed as an M-class mission in collaboration with the Russian space agency ROSCOSMOS.
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| 7. |
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| 8. |
- Carmona-Gutierrez, D., et al.
(author)
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Guidelines and recommendations on yeast cell death nomenclature
- 2018
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In: Microbial Cell. - : Shared Science Publishers OG. - 2311-2638. ; 5:1, s. 4-31
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Research review (peer-reviewed)abstract
- Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research.
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| 9. |
- Leloudas, G., et al.
(author)
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The superluminous transient ASASSN-15lh as a tidal disruption event from a Kerr black hole
- 2016
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In: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; 1:1
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Journal article (peer-reviewed)abstract
- When a star passes within the tidal radius of a supermassive black hole, it will be torn apart1. For a star with the mass of the Sun (M-circle dot) and a non-spinning black hole with a mass <10(8)M(circle dot), the tidal radius lies outside the black hole event horizon2 and the disruption results in a luminous flare(3-6). Here we report observations over a period of ten months of a transient, hitherto interpreted(7) as a superluminous supernova(8). Our data show that the transient rebrightened substantially in the ultraviolet and that the spectrum went through three different spectroscopic phases without ever becoming nebular. Our observations are more consistent with a tidal disruption event than a superluminous supernova because of the temperature evolution(6), the presence of highly ionized CNO gas in the line of sight(9) and our improved localization of the transient in the nucleus of a passive galaxy, where the presence of massive stars is highly unlikely(10,11). While the supermassive black hole has a mass >10(8)M(circle dot)(12,13), a star with the same mass as the Sun could be disrupted outside the event horizon if the black hole were spinning rapidly(14). The rapid spin and high black hole mass can explain the high luminosity of this event.
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| 10. |
- Perez-Nadales, Elena, et al.
(author)
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Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales : The impact of cytomegalovirus disease and lymphopenia
- 2020
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In: American Journal of Transplantation. - : WILEY. - 1600-6135 .- 1600-6143. ; 20:6, s. 1629-1641
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Journal article (peer-reviewed)abstract
- Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score >= 8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score >= 8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.
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| 11. |
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| 12. |
- Lazarus, Jeffrey V., et al.
(author)
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A multinational Delphi consensus to end the COVID-19 public health threat
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687.
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Journal article (peer-reviewed)abstract
- Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches1, while maintaining proven prevention measures using a vaccines-plus approach2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.
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| 13. |
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| 14. |
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| 15. |
- Gerhards, R, et al.
(author)
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Oligodendrocyte myelin glycoprotein as a novel target for pathogenic autoimmunity in the CNS
- 2020
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In: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 8:1, s. 207-
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Journal article (peer-reviewed)abstract
- Autoimmune disorders of the central nervous system (CNS) comprise a broad spectrum of clinical entities. The stratification of patients based on the recognized autoantigen is of great importance for therapy optimization and for concepts of pathogenicity, but for most of these patients, the actual target of their autoimmune response is unknown. Here we investigated oligodendrocyte myelin glycoprotein (OMGP) as autoimmune target, because OMGP is expressed specifically in the CNS and there on oligodendrocytes and neurons. Using a stringent cell-based assay, we detected autoantibodies to OMGP in serum of 8/352 patients with multiple sclerosis, 1/28 children with acute disseminated encephalomyelitis and unexpectedly, also in one patient with psychosis, but in none of 114 healthy controls. Since OMGP is GPI-anchored, we validated its recognition also in GPI-anchored form. The autoantibodies to OMGP were largely IgG1 with a contribution of IgG4, indicating cognate T cell help. We found high levels of soluble OMGP in human spinal fluid, presumably due to shedding of the GPI-linked OMGP. Analyzing the pathogenic relevance of autoimmunity to OMGP in an animal model, we found that OMGP-specific T cells induce a novel type of experimental autoimmune encephalomyelitis dominated by meningitis above the cortical convexities. This unusual localization may be directed by intrathecal uptake and presentation of OMGP by meningeal phagocytes. Together, OMGP-directed autoimmunity provides a new element of heterogeneity, helping to improve the stratification of patients for diagnostic and therapeutic purposes.
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| 16. |
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| 17. |
- King, C, et al.
(author)
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Population impact and effectiveness of sequential 13-valent pneumococcal conjugate and monovalent rotavirus vaccine introduction on infant mortality: prospective birth cohort studies from Malawi
- 2020
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In: BMJ global health. - : BMJ. - 2059-7908. ; 5:9
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Journal article (peer-reviewed)abstract
- Pneumococcal conjugate vaccine (PCV) and rotavirus vaccine (RV) are key tools for reducing common causes of infant mortality. However, measurement of population-level mortality impact is lacking from sub-Saharan Africa. We evaluated mortality impact and vaccine effectiveness (VE) of PCV13 introduced in November 2011, with subsequent RV1 roll-out in October 2012, in Malawi.MethodsWe conducted two independent community-based birth cohort studies. Study 1, in northern Malawi (40000population), evaluated population impact using change-point analysis and negative-binomial regression of non-traumatic 14–51-week infant mortality preintroduction (1 January 2004 to 31 September 2011) and postintroduction (1 October 2011 to 1 July 2019), and against three-dose coverage. Study 2, in central Malawi (465 000 population), was recruited from 24 November 2011 to 1 June 2015. In the absence of preintroduction data, individual three-dose versus zero-dose VE was estimated using individual-level Cox survival models. In both cohorts, infants were followed with household visits to ascertain vaccination, socioeconomic and survival status. Verbal autopsies were conducted for deaths.ResultsStudy 1 included 20 291 live births and 216 infant deaths. Mortality decreased by 28.6% (95% CI: 15.3 to 39.8) post-PCV13 introduction. A change point was identified in November 2012. Study 2 registered 50 731 live births, with 454 deaths. Infant mortality decreased from 17 to 10/1000 live births during the study period. Adjusted VE was 44.6% overall (95% CI: 23.0 to 59.1) and 48.3% (95% CI: −5.9 to 74.1) against combined acute respiratory infection, meningitis and sepsis-associated mortality.ConclusionThese data provide population-level evidence of infant mortality reduction following sequential PCV13 and RV1 introduction into an established immunisation programme in Malawi. These data support increasing coverage of vaccine programmes in high-burden settings.
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| 18. |
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| 19. |
- Loh, P, et al.
(author)
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Added value of an open narrative in verbal autopsies: a mixed-methods evaluation from Malawi
- 2021
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In: BMJ paediatrics open. - : BMJ. - 2399-9772. ; 5:1, s. e000961-
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Journal article (peer-reviewed)abstract
- The WHO standardised verbal autopsy (VA) instrument includes closed questions, ascertaining signs and symptoms of illness preceding death, and an optional open narrative. As VA analyses increasingly use automated algorithms, inclusion of narratives should be justified. We evaluated the role of open narratives on VA processes, data quality and respondent’s emotional stress.MethodsA mixed-methods analysis was conducted using VA data for child deaths (0–59 months), between April 2013 and November 2016 in Mchinji district, Malawi. Deaths were prospectively randomised to receive closed questions only or open narrative followed by closed questions. On concluding the VA, interviewers self-completed questions on respondents’ emotional stress. Logistic regression was used to determine associations with visible emotional distress during VAs. A group discussion with interviewers was conducted at the project end, to understand field experiences and explore future recommendations; data were coded using deductive themes.Results2509 VAs were included, with 49.8% (n=1341) randomised to open narratives. Narratives lasted a median of 7 minuntes (range: 1–113). Interviewers described improved rapport and felt narratives improved data quality, although there was no difference in the proportion of deaths with an indeterminate cause using an automated algorithm (5.3% vs 6.1%). The majority of respondents did not display visible emotional stress (81%). Those with a narrative had higher, but not statistically significant, odds of emotional distress (adjusted OR: 1.20; 95% CI: 0.98 to 1.47). Factors associated with emotional stress were: infant deaths versus neonates; deaths at a health centre or en-route to hospital versus home; and higher socioeconomic status. Non-parental respondents and increased time between death and interview were associated with lower odds of emotional distress.ConclusionConducting an open narrative may help build rapport, something valued by the interviewers. However, additional time and emotional burdens should be further justified, with quality and utility of narratives promoted through standardised recommendations.
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| 20. |
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| 21. |
- Villarroel, Beatriz, et al.
(author)
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The Vanishing and Appearing Sources during a Century of Observations Project. I. USNO Objects Missing in Modern Sky Surveys and Follow-up Observations of a "Missing Star"
- 2020
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In: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 159:1
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Journal article (peer-reviewed)abstract
- In this paper we report the current status of a new research program. The primary goal of the "Vanishing and Appearing Sources during a Century of Observations" project is to search for vanishing and appearing sources using existing survey data to find examples of exceptional astrophysical transients. The implications of finding such objects extend from traditional astrophysics fields to the more exotic searches for evidence of technologically advanced civilizations. In this first paper we present new, deeper observations of the tentative candidate discovered by Villarroel et al. in 2016. We then perform the first searches for vanishing objects throughout the sky by comparing 600 million objects from the US Naval Observatory Catalogue (USNO) B1.0 down to a limiting magnitude of similar to 20-21 with the recent Pan-STARRS Data Release-1 (DR1) with a limiting magnitude of similar to 23.4. We find about 150,000 preliminary candidates that do not have any Pan-STARRS counterpart within a 30 '' radius. We show that these objects are redder and have larger proper motions than typical USNO objects. We visually examine the images for a subset of about 24,000 candidates, superseding the 2016 study with a sample 10 times larger. We find about 100 point sources visible in only one epoch in the red band of the USNO, which may be of interest in searches for strong M-dwarf flares, high-redshift supernovae, or other categories of unidentified red transients.
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| 22. |
- Abulafia, C., et al.
(author)
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Relationship between Cognitive and Sleep-wake Variables in Asymptomatic Offspring of Patients with Late-onset Alzheimer's Disease
- 2017
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In: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 9
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Journal article (peer-reviewed)abstract
- Early neuropathological changes characteristic of late-onset Alzheimer's disease (LOAD) involve brain stem and limbic structures that regulate neurovegetative functions, including sleep-wake rhythm. Indeed, sleep pattern is an emerging biomarker and a potential pathophysiological mechanism in LOAD. We hypothesized that cognitively asymptomatic, middle-aged offspring of patients with LOAD (O-LOAD) would display a series of circadian rhythm abnormalities prior to the onset of objective cognitive alterations. We tested 31 children of patients with LOAD (O-LOAD) and 19 healthy individuals without family history of Alzheimer's disease (control subjects, CS) with basic tests of cognitive function, as well as actigraphy measures of sleep-wake rhythm, cardiac autonomic function, and bodily temperature. Unexpectedly, O-LOAD displayed subtle but significant deficits in verbal episodic memory (Rey Auditory Verbal Learning Test delayed recall 10.6 +/- 0.4 vs. 8.6 +/- 0.6, t = 4.97, df = 49, p < 0.01) and language (Weschler's vocabulary 51.4 +/- 1.3 vs. 44.3 +/- 1.5, t = 2.49, df = 49, p < 0.001) compared to CS, even though all participants had results within the clinically normal range. O-LOAD showed a phase-delayed rhythm of body temperature (2.56 +/- 0.47 h vs. 3.8 +/- 0.26 h, t = 2.48, df = 40, p = 0.031). Cognitive performance in O-LOAD was associated with a series of cardiac autonomic sleep-wake variables; specifically indicators of greater sympathetic activity at night were related to poorer cognition. The present results suggest sleep pattern deserves further study as a potential neurobiological signature in LOAD, even in middle-aged, at risk individuals.
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| 23. |
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| 24. |
- Bergström, Anders, et al.
(author)
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Origins and genetic legacy of prehistoric dogs
- 2020
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 370:6516, s. 557-563
-
Journal article (peer-reviewed)abstract
- Dogs were the first domestic animal, but little is known about their population history and to what extent it was linked to humans. We sequenced 27 ancient dog genomes and found that all dogs share a common ancestry distinct from present-day wolves, with limited gene flow from wolves since domestication but substantial dog-to-wolf gene flow. By 11,000 years ago, at least five major ancestry lineages had diversified, demonstrating a deep genetic history of dogs during the Paleolithic. Coanalysis with human genomes reveals aspects of dog population history that mirror humans, including Levant-related ancestry in Africa and early agricultural Europe. Other aspects differ, including the impacts of steppe pastoralist expansions in West and East Eurasia and a near-complete turnover of Neolithic European dog ancestry.
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| 25. |
- Campion, Otto Bulmaniya, et al.
(author)
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Monitoring and evaluation of Indigenous Land and Sea Management : An Indigenous-led approach in the Arafura Swamp, northern Australia
- 2023
-
In: Ecological Management & Restoration. - 1442-7001 .- 1442-8903. ; 24:2-3, s. 75-88
-
Journal article (peer-reviewed)abstract
- As Indigenous Land and Sea Management has grown in scope and scale, there has been increasing focus on monitoring and evaluation to foster learning, strengthen accountability and report on outcomes. A resurgence in Indigenous governance has led to recognition that Indigenous knowledge, law and governance systems are essential to successful conservation initiatives on Indigenous lands. Indigenous-led monitoring and evaluation involves Indigenous Peoples exercising control, direction and informed decisions about monitoring and evaluation practices and signals a greater role for Indigenous methodologies alongside participatory approaches and Western sciences. This Article describes the Intercultural Monitoring and Evaluation Project, led by the Arafura Swamp Rangers Aboriginal Corporation in partnership with Bi and Yolŋu Traditional Owners and clans and non-Indigenous practitioners and researchers. The Intercultural Monitoring and Evaluation Project aimed to co-produce an Indigenous-led and Country-based monitoring and evaluation system for Arafura Swamp Rangers Aboriginal Corporation's Healthy Country Plan. The Intercultural Monitoring and Evaluation Project recognised that the Rangers from the Arafura Swamp Rangers Aboriginal Corporation are accountable within Bi, Yolŋu and Western governance systems and that monitoring and evaluation at Arafura Swamp Rangers Aboriginal Corporation needed to strengthen relationships between all three. The Intercultural Monitoring and Evaluation Project involved: (i) developing understandings of monitoring and evaluation in Bi, Yolŋu and Western knowledge systems, (ii) generating organisational roadmaps, targets and indicators, (iii) developing Bi, Yolŋu and Western monitoring methods, (iv) building a data management system and seasonal monitoring calendar, (v) initiating a monitoring and evaluation committee to inform Arafura Swamp Rangers Aboriginal Corporation's strategic decision-making and (vi) sharing the story of the project with others. This approach embedded monitoring and evaluation in Indigenous law and governance, oral knowledge traditions and the intergenerational kinship relationships that sustain people and Country, while also connecting to Western adaptive management frameworks. Indigenous-led approaches can integrate monitoring and evaluation with Indigenous practices of caring for Country, contributing directly to the multiple ecological, cultural and socio-economic goals of Indigenous Land and Sea Management.
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| 26. |
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Garcia, Arturo S., et al.
(author)
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A collaborative workspace architecture for strengthening collaboration among space scientists
- 2015
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In: Proceedings of a meeting held 7-14 March 2015, Big Sky, Montana, USA.. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781479953790 - 9781479953806 - 9781479953776 ; , s. 1133-1144
-
Conference paper (peer-reviewed)abstract
- Space exploration missions have produced large data of immense value, to both research and the planning and operating of future missions. However, current datasets and simulation tools fragment teamwork, especially across disciplines and geographical location. The aerospace community already exploits virtual reality for purposes including space tele-robotics, interactive 3D visualization, simulation and training. However, collaborative virtual environments are yet to be widely deployed or routinely used in space projects. Advanced immersive and collaborative visualization systems have the potential for enhancing the efficiency and efficacy of data analysis, simplifying visual benchmarking, presentations and discussions. We present preliminary results of the EU funded international project CROSS DRIVE, which develops an infrastructure for collaborative workspaces for space science and missions. The aim is to allow remote scientific and engineering experts to collectively analyze and interpret combined datasets using shared simulation tools. The approach is to combine advanced 3D visualization techniques and interactive tools in conjunction with immersive virtuality telepresence. This will give scientists and engineers the impression of teleportation from their respective buildings across Europe, to stand together on a planetary surface, surrounded by the information and tools that they need. The conceptual architecture and proposed realization of the collaborative workspace are described. ESA's planned ExoMars mission provides the use-case for deriving user requirements and evaluating our implementation.
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| 31. |
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| 32. |
- Hindricks, Gerhard, et al.
(author)
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Ability to remotely monitor atrial high-rate episodes using a single-chamber implantable cardioverter-defibrillator with a floating atrial sensing dipole
- 2023
-
In: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 25:5
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Journal article (peer-reviewed)abstract
- Aims: To allow timely initiation of anticoagulation therapy for the prevention of stroke, the European guidelines on atrial fibrillation (AF) recommend remote monitoring (RM) of device-detected atrial high-rate episodes (AHREs) and progression of arrhythmia duration along pre-specified strata (6 min...<1h, 1 h...<24 h, >= 24h). We used the MATRIX registry data to assess the capability of a single-lead implantable cardioverter-defibrillator (ICD) with atrial sensing dipole (DX ICD system) to follow this recommendation in patients with standard indication for single-chamber ICD.Methods and results: In 1841 DX ICD patients with daily automatic RM transmissions, electrograms of first device-detected AHREs per patient in each duration stratum were adjudicated, and the corresponding positive predictive values (PPVs) for the detections to be true atrial arrhythmia were calculated. Moreover, the incidence and progression of new-onset AF was assessed in 1451 patients with no AF history. A total of 610 AHREs >= 6min were adjudicated. The PPV was 95.1% (271 of 285) for episodes 6min...<1h, 99.6% (253/254) for episodes 1 h...<24h, 100% (71/71) for episodes >= 24h, or 97.5% for all episodes (595/610). The incidence of new-onset AF was 8.2% (119/1451), and in 31.1% of them (37/119), new-onset AF progressed to a higher duration stratum. Nearly 80% of new-onset AF patients had high CHA(2)DS(2)-VASc stroke risk, and 70% were not on anticoagulation therapy. Age was the only significant predictor of new-onset AF.Conclusion: A 99.7% detection accuracy for AHRE >= 1h in patients with DX ICD systems in combination with daily RM allows a reliable guideline-recommended screening for subclinical AF and monitoring of AF-duration progression.
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| 33. |
- Illini, Oliver, et al.
(author)
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Real-world experience with capmatinib in MET exon 14-mutated non-small cell lung cancer (RECAP) : a retrospective analysis from an early access program
- 2022
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In: Therapeutic Advances in Medical Oncology. - : Sage Publications. - 1758-8340 .- 1758-8359. ; 14
-
Journal article (peer-reviewed)abstract
- Background: Patients with non-small cell lung cancer (NSCLC) presenting with mesenchymal-epithelial transition (MET) exon 14 skipping mutation have an unfavorable prognosis with standard treatments. Capmatinib is a selective MET inhibitor, which showed promising efficacy in this patient population in early trials. Methods: We performed a retrospective, international, multicenter efficacy and safety analysis in patients with NSCLC treated with capmatinib in an early access program between March 2019 and December 2021. Results: Data from 81 patients with advanced MET exon 14 mutated NSCLC treated with capmatinib in first- or later-line therapy were analyzed. Median age was 77 years (range, 48-91), 56% were women, 86% had stage IV disease, and 27% had brain metastases. For all patients, the objective response rate (ORR) to capmatinib was 58% (95% CI, 47-69), whereas it was 68% (95% CI, 50-82) in treatment-naive and 50% (95% CI, 35-65) in pretreated patients. The median progression-free survival was 9.5 months (95% CI, 4.7-14.3), whereas it was 10.6 months (95% CI, 5.5-15.7) in first-line and 9.1 months (95% CI, 3.1-15.1) in pretreated patients. After a median follow-up of 11.0 months, the median overall survival was 18.2 months (95% CI, 13.2-23.1). In patients with measurable brain metastases (n = 11), the intracranial ORR was 46% (95% CI, 17-77). Capmatinib showed a manageable safety profile. Grade > 3 treatment-related adverse events included peripheral edema (13%), elevated creatinine (4%), and elevated liver enzymes (3%). Conclusion: In patients with MET exon 14 skipping mutation, capmatinib showed durable systemic and intracranial efficacy and a manageable safety profile. This analysis confirms previously reported phase II data in a real-world setting.
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| 34. |
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| 35. |
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| 36. |
- Kappos, Ludwig, et al.
(author)
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Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
- 2018
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 391, s. 1263-1273
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Journal article (peer-reviewed)abstract
- © 2018 Elsevier Ltd Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatme nt arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation: Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding: Novartis Pharma AG.
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| 37. |
- King, C, et al.
(author)
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Care-seeking patterns amongst suspected paediatric pneumonia deaths in rural Malawi
- 2020
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In: Gates open research. - : F1000 Research Ltd. - 2572-4754. ; 4, s. 178-
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Journal article (peer-reviewed)abstract
- Background: Pneumonia remains a leading cause of paediatric deaths. To understand contextual challenges in care pathways, we explored patterns in care-seeking amongst children who died of pneumonia in Malawi. Methods: We conducted a mixed-methods analysis of verbal autopsies (VA) amongst deaths in children aged 1-59 months from 10/2011 to 06/2016 in Mchinji district, Malawi. Suspected pneumonia deaths were defined as: 1. caregiver reported cough and fast breathing in the 2-weeks prior to death; or, 2. the caregiver specifically stated the child died of pneumonia; or 3. cause of death assigned as ‘acute respiratory infection’ using InterVA-4. Data were extracted from free-text narratives based on domains in the ‘Pathways to Survival’ framework, and described using proportions. Qualitative analysis used a framework approach, with pre-specified themes. Results: We analysed 171 suspected pneumonia deaths. In total, 86% of children were taken to a healthcare facility during their final illness episode, and 44% sought care more than once. Of children who went to hospital (n=119), 70% were admitted, and 25% received oxygen. Half of the children died within a healthcare setting (43% hospital, 5% health centre and 2% private clinics), 64 (37%) at home, and 22 (13%) in transit. Challenges in delayed care, transport and quality of care (including oxygen), were reported. Conclusions: Healthcare was frequently sought for children who died of suspected pneumonia, however several missed opportunities for care were seen. Sustained investment in timely appropriate care seeking, quick transportation to hospital and improved case management at all levels of the system is needed.
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| 38. |
- Krueger, P., et al.
(author)
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Potential roughness near lithographically fabricated atom chips
- 2007
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In: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 76:6
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Journal article (peer-reviewed)abstract
- Potential roughness has been reported to severely impair experiments in magnetic microtraps. We show that these obstacles can be overcome as we measure disorder potentials that are reduced by two orders of magnitude near lithographically patterned high-quality gold layers on semiconductor atom chip substrates. The spectrum of the remaining field variations exhibits a favorable scaling. A detailed analysis of the magnetic field roughness of a 100-mu m-wide wire shows that these potentials stem from minute variations of the current flow caused by local properties of the wire rather than merely from rough edges. A technique for further reduction of potential roughness by several orders of magnitude based on time-orbiting magnetic fields is outlined.
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| 40. |
- Kruger, P., et al.
(author)
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Ultracold atoms on atom chips : Manipulation at the mu m distance scale
- 2005
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In: ATOMIC PHYSICS 19. - : AIP. ; , s. 144-153
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Conference paper (peer-reviewed)abstract
- Miniaturized potentials near the surface of atom chips can be used as flexible and versatile tools for the manipulation of ultracold atoms on a microscale. The full scope of possibilities is only accessible if atom‐surface distances can be reduced to microns. We discuss experiments in this regime and potential obstacles and solutions. We show that appropriate fabrication techniques lead to a reduction of disorder potentials so that one‐dimensional condensates can be prepared. We demonstrate how electrostatic potentials can be used to modify magnetic trapping potentials and how they can be used to study condensate formation in situations of different dimensionality. © 2005 American Institute of Physics
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| 49. |
- Roe, Mícheál D, et al.
(author)
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Professor Ed Cairns: A personal and professional biography.
- 2014
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In: Peace and Conflict: The Journal of Peace Psychology. - : American Psychological Association (APA). - 1078-1919 .- 1532-7949. ; 20:1, s. 3-12
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Journal article (other academic/artistic)abstract
- This article provides a brief overview of Ed Cairns’ (1945–2012) personal and professional life. Born, raised, and educated in Belfast, Ed’s career at the University of Ulster spanned the years of Northern Ireland’s contemporary political violence—from the riots of the early 1970s, through the Good Friday Agreement of 1998, and into the present postconflict period. A fellow of both the British Psychological Society and the American Psychological Association, Ed was a leading international scholar on social identity, conflict and peace, and children and political violence. He was a committed teacher and mentor of many university students and of many peace psychologists from around the globe. He was also an influential leader worldwide and the first international President of APA’s Division 48, the Society for the Study of Peace, Conflict, and Violence.
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| 50. |
- Schumm, T., et al.
(author)
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A double well interferometer on an atom chip
- 2006
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In: Quantum Information Processing. - : Springer Science and Business Media LLC. - 1570-0755 .- 1573-1332. ; 5:6, s. 537-558
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Journal article (peer-reviewed)abstract
- Radio-Frequency coupling between magnetically trapped atomic states allows to create versatile adiabatic dressed state potentials for neutral atom manipulation. Most notably, a single magnetic trap can be split into a double well by controlling amplitude and frequency of an oscillating magnetic field. We use this to build an integrated matter wave interferometer on an atom chip. Transverse splitting of quasi one-dimensional Bose-Einstein condensates over a wide range from 3 to 80 mu m is demonstrated, accessing the tunnelling regime as well as completely isolated sites. By recombining the two split BECs in time of flight expansion, we realize a matter wave interferometer. The observed interference pattern exhibits a stable relative phase of the two condensates, clearly indicating a coherent splitting process. Furthermore, we measure and control the deterministic phase evolution throughout the splitting process. RF induced potentials are especially suited for integrated micro manipulation of neutral atoms on atom chips: designing appropriate wire patterns enables control over the created potentials to the (nanometer) precision of the fabrication process. Additionally, hight local RF amplitudes can be obtained with only moderate currents. This new technique can be directly implemented in many existing atom chip experiments.
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