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- Scelo, Ghislaine, et al.
(författare)
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Exploring Definitions and Predictors of Response to Biologics for Severe Asthma
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Ingår i: Journal of Allergy and Clinical Immunology: In Practice. - 2213-2198.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging. Objective: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response. Methods: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV1. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis. Results: A total of 2,210 patients were included. Responder rate ranged from 80.7% (n = 566 of 701) for exacerbation response to 10.6% (n = 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n = 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio = 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio = 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria. Conclusions: Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed. © 2024 The Authors
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- Kim, Jinhan, et al.
(författare)
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Evaluating Surprise Adequacy for Deep Learning System Testing
- 2023
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Ingår i: ACM Transactions on Software Engineering and Methodology. - : Association for Computing Machinery (ACM). - 1049-331X .- 1557-7392. ; 32:2
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Tidskriftsartikel (refereegranskat)abstract
- The rapid adoption of Deep Learning (DL) systems in safety critical domains such as medical imaging and autonomous driving urgently calls for ways to test their correctness and robustness. Borrowing from the concept of test adequacy in traditional software testing, existing work on testing of DL systems initially investigated DL systems from structural point of view, leading to a number of coverage metrics. Our lack of understanding of the internal mechanism of Deep Neural Networks (DNNs), however, means that coverage metrics defined on the Boolean dichotomy of coverage are hard to intuitively interpret and understand. We propose the degree of out-of-distribution-ness of a given input as its adequacy for testing: the more surprising a given input is to the DNN under test, the more likely the system will show unexpected behavior for the input. We develop the concept of surprise into a test adequacy criterion, called Surprise Adequacy (SA). Intuitively, SA measures the difference in the behavior of the DNN for the given input and its behavior for the training data. We posit that a good test input should be sufficiently, but not overtly, surprising compared to the training dataset. This article evaluates SA using a range of DL systems from simple image classifiers to autonomous driving car platforms, as well as both small and large data benchmarks ranging from MNIST to ImageNet. The results show that the SA value of an input can be a reliable predictor of the correctness of the mode behavior. We also show that SA can be used to detect adversarial examples, and also be efficiently computed against large training dataset such as ImageNet using sampling.
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- Tatzelt, C., et al.
(författare)
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Circum-Antarctic abundance and properties of CCN and INPs
- 2022
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 22:14, s. 9721-9745
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Tidskriftsartikel (refereegranskat)abstract
- Aerosol particles acting as cloud condensation nuclei (CCN) or ice-nucleating particles (INPs) play a major role in the formation and glaciation of clouds. Thereby they exert a strong impact on the radiation budget of the Earth. Data on abundance and properties of both types of particles are sparse, especially for remote areas of the world, such as the Southern Ocean (SO). In this work, we present unique results from ship-borne aerosol-particle-related in situ measurements and filter sampling in the SO region, carried out during the Antarctic Circumnavigation Expedition (ACE) in the austral summer of 2016-2017. An overview of CCN and INP concentrations over the Southern Ocean is provided and, using additional quantities, insights regarding possible CCN and INP sources and origins are presented. CCN number concentrations spanned 2 orders of magnitude, e.g. for a supersaturation of 0.3% values ranged roughly from 3 to 590 cm(-3). CCN showed variable contributions of organic and inorganic material (inter-quartile range of hygroscopicity parameter kappa from 0.2 to 0.9). No distinct size dependence of kappa was apparent, indicating homogeneous composition across sizes (critical dry diameter on average between 30 and 110 nm). The contribution of sea spray aerosol (SSA) to the CCN number concentration was on average small. Ambient INP number concentrations were measured in the temperature range from -5 to -27 degrees C using an immersion freezing method. Concentrations spanned up to 3 orders of magnitude, e.g. at -16 degrees C from 0.2 to 100 m(-3). Elevated values (above 10 m(-3) at 16 degrees C) were measured when the research vessel was in the vicinity of land (excluding Antarctica), with lower and more constant concentrations when at sea. This, along with results of backward-trajectory analyses, hints towards terrestrial and/or coastal INP sources being dominant close to ice-free (non-Antarctic) land. In pristine marine areas INPs may originate from both oceanic sources and/or long-range transport. Sampled aerosol particles (PM10) were analysed for sodium and methanesulfonic acid (MSA). Resulting mass concentrations were used as tracers for primary marine and secondary aerosol particles, respectively. Sodium, with an average mass concentration around 2.8 mu gm(-3), was found to dominate the sampled, identified particle mass. MSA was highly variable over the SO, with mass concentrations up to 0.5 mu g m(-3) near the sea ice edge. A correlation analysis yielded strong correlations between sodium mass concentration and particle number concentration in the coarse mode, unsurprisingly indicating a significant contribution of SSA to that mode. CCN number concentration was highly correlated with the number concentration of Aitken and accumulation mode particles. This, together with a lack of correlation between sodium mass and Aitken and accumulation mode number concentrations, underlines the important contribution of non-SSA, probably secondarily formed particles, to the CCN population. INP number concentrations did not significantly correlate with any other measured aerosol physico-chemical parameter.
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- Patrignani, Norberto, et al.
(författare)
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On the Complex Relationship Between ICT Systems and the Planet
- 2018
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Ingår i: This Changes Everything –ICT and Climate Change. - Cham : Springer. - 9783319996042 ; , s. 181-187
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Konferensbidrag (refereegranskat)abstract
- This paper addresses the challenges of designing sustainable Information and Communication Technology (ICT) systems. The complexity of ICT systems, the number of stakeholders involved (technology providers, policymakers, users, etc.), and the extension and global scale of ICT supply chain are the main challenges at the core of the complex relationship between ICT systems and the planet Earth. ICT offer an opportunity for an exchange between matter-energy and information: the better use of information offers the greatopportunity for decreasing the environmental impact of human activities by decreasing the matter and energy consumption. But, on the other side, like anyhuman activity, the design, production, use, and disposal of complex ICT systems,has as a consequence a growth in entropy. This intriguing dilemma is one of the most difficult challenges in front of designers, ICT companies, users, and policy makers. This paper concentrates on the designers, the engineers’ dilemmas: what are the ethical competences, the skills, the methods for addressing these complex ethical dilemmas? Among the many ethical approaches, the“virtue/future ethics” is proposed as a core ethical competence for the designers and engineers of the future.
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6. |
- Beato, Marco, et al.
(författare)
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Current Guidelines for the Implementation of Flywheel Resistance Training Technology in Sports: A Consensus Statement
- 2024
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Ingår i: Sports Medicine. - : ADIS INT LTD. - 0112-1642 .- 1179-2035.
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Forskningsöversikt (refereegranskat)abstract
- BackgroundFlywheel resistance training has become more integrated within resistance training programs in a variety of sports due to the neuromuscular, strength, and task-specific enhancements reported with this training.ObjectiveThis paper aimed to present the consensus reached by internationally recognized experts during a meeting on current definitions and guidelines for the implementation of flywheel resistance training technology in sports.MethodsNineteen experts from different countries took part in the consensus process; 16 of them were present at the consensus meeting (18 May 2023) while three submitted their recommendations by e-mail. Prior to the meeting, evidence summaries were developed relating to areas of priority. This paper discusses the available evidence and consensus process from which recommendations were made regarding the appropriate use of flywheel resistance training technology in sports. The process to gain consensus had five steps: (1) performing a systematic review of systematic reviews, (2) updating the most recent umbrella review published on this topic, (3) first round discussion among a sample of the research group included in this consensus statement, (4) selection of research group members-process of the consensus meeting and formulation of the recommendations, and (5) the consensus process. The systematic analysis of the literature was performed to select the most up-to-date review papers available on the topic, which resulted in nine articles; their methodological quality was assessed according to AMSTAR 2 (Assessing the Methodological Quality of Systematic Review 2) and GRADE (Grading Recommendations Assessment Development and Evaluation). Statements and recommendations scoring 7-9 were considered appropriate.ResultsThe recommendations were based on the evidence summary and researchers' expertise; the consensus statement included three statements and seven recommendations for the use of flywheel resistance training technology. These statements and recommendations were anonymously voted on and qualitatively analyzed. The three statements reported a score ranging from 8.1 to 8.8, and therefore, all statements included in this consensus were considered appropriate. The recommendations (1-7) had a score ranging from 7.7 to 8.6, and therefore, all recommendations were considered appropriate.ConclusionsBecause of the consensus achieved among the experts in this project, it is suggested that practitioners and researchers should adopt the guidelines reported in this consensus statement regarding the use of flywheel resistance technology in sports.
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8. |
- Beate Larsen, Inger, et al.
(författare)
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You realise you are better when you want to live, want to go out, want to see people : Recovery as assemblage
- 2021
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Ingår i: International Journal of Social Psychiatry. - : SAGE Publications. - 0020-7640 .- 1741-2854.
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Tidskriftsartikel (refereegranskat)abstract
- Background: The lack of social and material perspectives in descriptions of recovery processes is almost common in recovery research.Aim: Consequently, we investigated recovery stories and how people with mental health and/or addiction challenges included social and material aspects in these stories.Method: We conducted focus group and individual interviews. We investigated how the participants narrated their stories and how they assembled places and people in their recovery stories.Results: We found that narratives of recovery became assemblages where humans and their environments co-exist and are interdependent.Conclusion: As such, narratives about recovery are about everyday assemblages of well-being into which stories of insecurity are interwoven, without a start or stop point.
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10. |
- Lu, Jian, et al.
(författare)
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The Kluyveromyces lactis γ-toxin targets tRNA anticodons.
- 2005
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Ingår i: RNA. - : Cold Spring Harbor Laboratory. - 1355-8382 .- 1469-9001. ; 11:11, s. 1648-1654
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Tidskriftsartikel (refereegranskat)abstract
- Kluyveromyces lactis killer strains secrete a heterotrimeric toxin (zymocin), which causes an irreversible growth arrest of sensitive yeast cells. Despite many efforts, the target(s) of the cytotoxic gamma-subunit of zymocin has remained elusive. Here we show that three tRNA species tRNA(Glu)(mcm(5)s(2)UUC), tRNA(Lys)(mcm(5)s(2)UUU), and tRNA(Gln)(mcm(5)s(2)UUG) are the targets of gamma-toxin. The toxin inhibits growth by cleaving these tRNAs at the 3' side of the modified wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U). Transfer RNA lacking a part of or the entire mcm(5) group is inefficiently cleaved by gamma-toxin, explaining the gamma-toxin resistance of the modification-deficient trm9, elp1-elp6, and kti11-kti13 mutants. The K. lactis gamma-toxin is the first eukaryotic toxin shown to target tRNA.
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