| 1. |
- Ekelund, Rebecka, et al.
(författare)
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Interventions for improving mental health in athletes : a scoping review
- 2023
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Ingår i: International Review of Sport and Exercise Psychology. - Oxon : Routledge. - 1750-984X .- 1750-9858.
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Forskningsöversikt (refereegranskat)abstract
- The aims of this scoping review were to map the current literature on interventions for improving mental health in athletes, identify knowledge gaps, and generate future research questions. The Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guided this review. A systematic literature search was conducted in SPORTDiscus, PsycINFO, and SCOPUS and 44 intervention studies met the inclusion criteria. Results showed that 22 studies (50%) implemented cognitive behavioural principles, and the majority of these studies were influenced by various mindfulness programmes. Most studies (93%) included healthy athlete samples, and athletes aged 15–19 were the most examined age group (43%). Only three studies used clinical criteria in their sampling of participants and mediators were examined in two studies. The scarcity of studies examining mediators and subclinical or clinical samples revealed critical knowledge gaps in the literature. Furthermore, the critical appraisal showed that regardless of study design, most studies demonstrated low internal validity. We propose the use of high-quality single-case studies with athletes who experience subclinical or clinical mental health issues, and further investigation of mechanisms of change linking intervention components to outcomes of interest.
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| 2. |
- Kirchhof, Paulus, et al.
(författare)
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Comprehensive risk reduction in patients with atrial fibrillation : emerging diagnostic and therapeutic options - a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference
- 2012
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 14:1, s. 8-27
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Forskningsöversikt (refereegranskat)abstract
- While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF.
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| 3. |
- Ahmed, Fozia Z., et al.
(författare)
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Use of healthcare claims to validate the Prevention of Arrhythmia Device Infection Trial cardiac implantable electronic device infection risk score
- 2021
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 23:9, s. 1446-1455
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The Prevention of Arrhythmia Device Infection Trial (PADIT) infection risk score, developed based on a large prospectively collected data set, identified five independent predictors of cardiac implantable electronic device (CIED) infection. We performed an independent validation of the risk score in a data set extracted from U.S. healthcare claims.METHODS AND RESULTS: Retrospective identification of index CIED procedures among patients aged ≥18 years with at least one record of a CIED procedure between January 2011 and September 2014 in a U.S health claims database. PADIT risk factors and major CIED infections (with system removal, invasive procedure without system removal, or infection-attributable death) were identified through diagnosis and procedure codes. The data set was randomized by PADIT score into Data Set A (60%) and Data Set B (40%). A frailty model allowing multiple procedures per patient was fit using Data Set A, with PADIT score as the only predictor, excluding patients with prior CIED infection. A data set of 54 042 index procedures among 51 623 patients with 574 infections was extracted. Among patients with no history of prior CIED infection, a 1 unit increase in the PADIT score was associated with a relative 28% increase in infection risk. Prior CIED infection was associated with significant incremental predictive value (HR 5.66, P < 0.0001) after adjusting for PADIT score. A Harrell's C-statistic for the PADIT score and history of prior CIED infection was 0.76.CONCLUSION: The PADIT risk score predicts increased CIED infection risk, identifying higher risk patients that could potentially benefit from targeted interventions to reduce the risk of CIED infection. Prior CIED infection confers incremental predictive value to the PADIT score.
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| 4. |
- Alsterholm, Mikael, 1977, et al.
(författare)
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Establishment and utility of SwedAD : a nationwide Swedish registry for patients with atopic dermatitis receiving systemic pharmacotherapy
- 2023
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 103
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Tidskriftsartikel (refereegranskat)abstract
- SwedAD, a Swedish nationwide registry for patients with atopic dermatitis receiving systemic pharmacotherapy, was launched on 1 September 2019. We describe here the establishment of a user-friendly registry to the benefit of patients with atopic dermatitis. By 5 November 2022, 38 clinics had recorded 931 treatment episodes in 850 patients with an approximate national coverage rate of 40%. Characteristics at enrolment included median Eczema Area and Severity Index (EASI) 10.2 (interquartile range 4.0, 19.4), Patient-Oriented Eczema Measure (POEM) 18.0 (10.0, 24.0), Dermatology Life Quality Index (DLQI) 11.0 (5.0, 19.0) and Peak Itch Numerical Rating Scale-11 (NRS-11) 6.0 (3.0, 8.0). At 3 months, median EASI was 3.2 (1.0, 7.3) and POEM, DLQI, and NRS-11 were improved. Regional coverage varied, reflecting the distribution of dermatologists, the ratio of public to private healthcare, and difficulties in recruiting certain clinics. This study highlights the importance of a nationwide registry when managing systemic pharmacotherapy of atopic dermatitis.
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| 5. |
- Amanullah, Rahman, et al.
(författare)
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Diversity in extinction laws of Type Ia supernovae measured between 0.2 and 2 μm
- 2015
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 453:3, s. 3300-3328
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Tidskriftsartikel (refereegranskat)abstract
- We present ultraviolet (UV) observations of six nearby Type Ia supernovae (SNe Ia) obtained with the Hubble Space Telescope, three of which were also observed in the near-IR (NIR) with Wide-Field Camera 3. UV observations with the Swift satellite, as well as ground-based optical and NIR data provide complementary information. The combined data set covers the wavelength range 0.2-2 mu m. By also including archival data of SN 2014J, we analyse a sample spanning observed colour excesses up to E(B - V) = 1.4 mag. We study the wavelength-dependent extinction of each individual SN and find a diversity of reddening laws when characterized by the total-to-selective extinction R-V. In particular, we note that for the two SNe with E(B - V) greater than or similar to 1 mag, for which the colour excess is dominated by dust extinction, we find R-V = 1.4 +/- 0.1 and R-V = 2.8 +/- 0.1. Adding UV photometry reduces the uncertainty of fitted R-V by similar to 50 per cent allowing us to also measure R-V of individual low-extinction objects which point to a similar diversity, currently not accounted for in the analyses when SNe Ia are used for studying the expansion history of the Universe.
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| 6. |
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| 7. |
- Andersson, H. Robert H., et al.
(författare)
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Flipping the Data Center Network : Increasing East-West Capacity Using Existing Hardware
- 2017
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Ingår i: 2017 IEEE 42nd Conference on Local Computer Networks (LCN), 9-12 Oct. 2017. - : IEEE. - 9781509065233 - 9781509065226 ; , s. 211-214
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Konferensbidrag (refereegranskat)abstract
- In today's datacenters, there is an increasing demand for more network traffic capacity. The majority of the increase in traffic is internal to the datacenter, i.e., it flows between different servers within the datacenter. This category of traffic is often referred to as east-west traffic and traditional hierarchical architectures are not well equipped to handle this type of traffic. Instead, they are better suited for the north-southbound traffic between hosts and the Internet. One suggested solution for this capacity problem is to adopt a folded CLOS topology, also known as spine-leaf, which often relies on software defined network (SDN) controllers to manage traffic. This paper shows that it is possible to implement a spine-leaf network using commodity-ofthe-shelf switches and thus improve the east-west traffic capacity. This can be obtained using low complexity configuration and edgerouting for load balancing, eliminating the need for a centralized SDN controller.
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| 8. |
- Andersson, Magnus, et al.
(författare)
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Vortex liquid properties in optimally doped and oxygen-deficient YBa2Cu3O7-delta single crystals
- 2000
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Ingår i: Physica. C, Superconductivity. - 0921-4534 .- 1873-2143. ; 332:1-4, s. 86-92
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Tidskriftsartikel (refereegranskat)abstract
- The electrical anisotropy, gamma = (m(c)/m(ab))(1/2), can easily be varied by changing the oxygen content in single crystals of YBa2Cu3O7-delta (YBCO); thus making this system useful as a test system For vortex dynamics in high-temperature superconductors (HTSC). Here, some recent results are reviewed. Measurements of the c-axis resistivity with the magnetic field B II ab-plane is shown to be a powerful tool in studying vortex velocity correlations both parallel and perpendicular to the applied field. In optimally doped crystals, we iind evidence that the in-plane vortex lattice melts at T-m into a disentangled vortex liquid, which looses its correlation along the c-axis at a higher temperature T-br > T-m. For weakly disordered crystals and magnetic fields B \\ c-axis, a relation between the vortex glass line and the magnetic field dependence of the characteristic energy, U*, in the pinned vortex liquid is proposed. This approach is shown to give support to our idea of describing the vortex glass resistivity in the liquid regime by a modified glass correlation Length, xi(g) = xi(0)\k(B)T/U-0 - 1\(-nu) which depends on the average pinning energy, Lr,, in the system [A. Rydh, O. Rapp, M. Andersson, Phys. Rev. Lett. 83 (1999) 1850].
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| 9. |
- Anthon, Carl Thomas, et al.
(författare)
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Thrombocytopenia and platelet transfusions in ICU patients : an international inception cohort study (PLOT-ICU)
- 2023
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Ingår i: Intensive Care Medicine. - 0342-4642. ; 49:11, s. 1327-1338
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Thrombocytopenia (platelet count < 150 × 10 9/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. METHODS: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses.RESULTS: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42).CONCLUSION: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.
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| 10. |
- Becher, Nina, et al.
(författare)
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Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24 h
- 2024
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 45:10, s. 837-849
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Patients with long atrial high-rate episodes (AHRE) ≥ 24 hours and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared to no anticoagulation in these patients.METHODS: This secondary prespecified analysis of NOAH-AFNET 6 examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared to placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and ECG-diagnosed atrial fibrillation.RESULTS: AHRE ≥24 hours were present at baseline in 259/2389 patients enrolled in NOAH-AFNET 6 (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc score 4). Clinical characteristics were not different from patients with shorter AHRE. During a median follow-up of 1.8 years, the primary outcome occurred in 9/132 patients with AHRE ≥24 hours (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). AHRE duration did not interact with the efficacy (p-interaction = 0.65) or safety (p-interaction = 0.98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 hours developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; p < 0.001).CONCLUSIONS: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.
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| 11. |
- Berbrick, Walter, et al.
(författare)
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Conflict Prevention and Security Cooperation in the Arctic Region : Frameworks of the Future
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report, Conflict Prevention and Security Cooperation in the Arctic Region: Frameworks for the Future, captures consensus of the Newport Arctic Scholars Initiative 2020 scholars. Building upon the 2018-2019 NASI work on the limitations of the current cooperative security fora in the Arctic region, this cohort explored existing international frameworks and assessed their abilities to ensure freedom and security in the Arctic through political-military means. NASI 2020 also examined existing frameworks to determine whether they enabled increased dialogue and maritime security cooperation in the region. The frameworks were further evaluated for their abilities to prevent and manage conflict and enhance cooperation on areas of common security and defense interests in the region. Scholars were tasked to identify new frameworks that could be useful in establishing – and maintaining – open channels of communication, preventing conflict, and enhancing cooperation on areas of common security and defense interests among nations and navies in the Arctic region. Finally, the group sought to identify practical arrangements for a future meeting or summit that could bring together states to enhance dialogue on security and cooperation in the Arctic region.
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| 12. |
- Bertaglia, Emanuele, et al.
(författare)
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Atrial high-rate episodes : prevalence, stroke risk, implications for management, and clinical gaps in evidence
- 2019
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 21:10, s. 1459-1467
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Forskningsöversikt (refereegranskat)abstract
- Self-terminating atrial arrhythmias are commonly detected on continuous rhythm monitoring, e.g. by pacemakers or defibrillators. It is unclear whether the presence of these arrhythmias has therapeutic consequences. We sought to summarize evidence on the prevalence of atrial high-rate episodes (AHREs) and their impact on risk of stroke. We performed a comprehensive, tabulated review of published literature on the prevalence of AHRE. In patients with AHRE, but without atrial fibrillation (AF), we reviewed the stroke risk and the potential risk/benefit of oral anticoagulation. Atrial high-rate episodes are found in 10-30% of AF-free patients. Presence of AHRE slightly increases stroke risk (0.8% to 1%/year) compared with patients without AHRE. Atrial high-rate episode of longer duration (e.g. those >24 h) could be associated with a higher stroke risk. Oral anticoagulation has the potential to reduce stroke risk in patients with AHRE but is associated with a rate of major bleeding of 2%/year. Oral anticoagulation is not effective in patients with heart failure or survivors of a stroke without AF. It remains unclear whether anticoagulation is effective and safe in patients with AHRE. Atrial high-rate episodes are common and confer a slight increase in stroke risk. There is true equipoise on the best way to reduce stroke risk in patients with AHRE. Two ongoing trials (NOAH-AFNET 6 and ARTESiA) will provide much-needed information on the effectiveness and safety of oral anticoagulation using non-vitamin K antagonist oral anticoagulants in patients with AHRE.
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| 13. |
- Boriani, Giuseppe, et al.
(författare)
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Safety and efficacy of dronedarone from clinical trials to real-world evidence : implications for its use in atrial fibrillation
- 2019
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 21:12, s. 1764-1775
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Tidskriftsartikel (refereegranskat)abstract
- Efficacy and safety of dronedarone was shown in the ATHENA trial for paroxysmal or persistent atrial fibrillation (AF) patients. Further trials revealed safety concerns in patients with heart failure and permanent AF. This review summarizes insights from recent real-world studies and meta-analyses, including reports on efficacy, with focus on liver safety, mortality risk in patients with paroxysmal/persistent AF, and interactions of dronedarone with direct oral anticoagulants. Reports of rapidly progressing liver failure in dronedarone-prescribed patients in 2011 led to regulatory cautions about potential liver toxicity. Recent real-world evidence suggests dronedarone liver safety profile is similar to other antiarrhythmics and liver toxicity could be equally common with many Class III antiarrhythmics. Dronedarone safety concerns (increased mortality in patients with permanent AF) were raised based on randomized controlled trials (RCT) (ANDROMEDA and PALLAS), but comedication with digoxin may have increased the mortality rates in PALLAS, considering the dronedarone-digoxin pharmacokinetic (PK) interaction. Real-world data on apixaban-dronedarone interactions and edoxaban RCT observations suggest no significant safety risks for these drug combinations. Median trough plasma concentrations of dabigatran 110 mg during concomitant use with dronedarone are at acceptable levels, while PK data on the rivaroxaban-dronedarone interaction are unavailable. In RCTs and real-world studies, dronedarone significantly reduces AF burden and cardiovascular hospitalizations, and demonstrates a low risk for proarrhythmia in patients with paroxysmal or persistent AF. The concerns on liver safety must be balanced against the significant reduction in hospitalizations in patients with non-permanent AF and low risk for proarrhythmias following dronedarone treatment.
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| 14. |
- Bruederle, Daniel, et al.
(författare)
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A comprehensive workflow for general-purpose neural modeling with highly configurable neuromorphic hardware systems
- 2011
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Ingår i: Biological Cybernetics. - : Springer Science and Business Media LLC. - 0340-1200 .- 1432-0770. ; 104:4-5, s. 263-296
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Tidskriftsartikel (refereegranskat)abstract
- In this article, we present a methodological framework that meets novel requirements emerging from upcoming types of accelerated and highly configurable neuromorphic hardware systems. We describe in detail a device with 45 million programmable and dynamic synapses that is currently under development, and we sketch the conceptual challenges that arise from taking this platform into operation. More specifically, we aim at the establishment of this neuromorphic system as a flexible and neuroscientifically valuable modeling tool that can be used by non-hardware experts. We consider various functional aspects to be crucial for this purpose, and we introduce a consistent workflow with detailed descriptions of all involved modules that implement the suggested steps: The integration of the hardware interface into the simulator-independent model description language PyNN; a fully automated translation between the PyNN domain and appropriate hardware configurations; an executable specification of the future neuromorphic system that can be seamlessly integrated into this biology-to-hardware mapping process as a test bench for all software layers and possible hardware design modifications; an evaluation scheme that deploys models from a dedicated benchmark library, compares the results generated by virtual or prototype hardware devices with reference software simulations and analyzes the differences. The integration of these components into one hardware-software workflow provides an ecosystem for ongoing preparative studies that support the hardware design process and represents the basis for the maturity of the model-to-hardware mapping software. The functionality and flexibility of the latter is proven with a variety of experimental results.
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| 15. |
- Brännström, Andreas, et al.
(författare)
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Kite Aerial Photography - Hué
- 2014
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Bok (populärvet., debatt m.m.)abstract
- The Kite Aerial Photography - Hué project started with the intention from Mattias Ericsson and me Micael Norberg to work artistically on a jointly project with students from di erent art schools and from di erent cultures. We had an idea of building bridges both artistically and culturally. We traveled to Hué in Vietnam in order to explore new ways to collaborate and nd new artistic meth- ods. We wanted to use kites and send our cameras up in the air to make aerial pictures. We tried to nd a way to control events and by that also control our artistic outcome and understanding. But in the The Kite Aerial Photography project we had no control. The weather controlled our kites. The place and the language controlled what we knew and understood. What was left was to look into ourself and negate a compromise. The leftovers became documentations of an experience.And now I am looking back at those events, wondering what really happened. I am using words, trying to create an image of my memories and of my experience - hot air, smells and noise. Experi- ences I can’t communicate fully in words. You as a viewer will never feel them and I will only remember them. We will also remember di erently. Every participant have their own image ofwhat happened during those days in Hué. The feeling of being di erent, not understanding and being an outsider made us all meet ourselves in di erent ways. We believed that language would build bridges of understanding, and maybe it did. But here we are now. A long time has passed since we returned from Hué. What we have left are images and memories. I remember smells and emotions and in this state between memory and fact a tension is created. A juxtaposition of con ict- ing feelings. I look at the photographs now with a new understanding. We tried to move out of our comfort-zone looking for the unseen, the enigma, where memory and re ection becomes a liminal state. I now realize that knowledge is not fact or truth, but a state that we can call ”not knowing”. A state which for me is the very basic for understanding, and by that becoming the very essence of art.
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| 16. |
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| 17. |
- Camm, A. John, et al.
(författare)
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AIM-AF : A Physician Survey in the United States and Europe
- 2022
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Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Guideline recommendations are the accepted reference for selection of therapies for rhythm control of atrial fibrillation (AF). This study was designed to understand physicians' treatment practices and adherence to guidelines.Methods and Results: The AIM-AF (Antiarrhythmic Medication for Atrial Fibrillation) study was an online survey of clinical cardiologists and electrophysiologists that was conducted in the United States and Europe (N=629). Respondents actively treated >= 30 patients with AF who received drug therapy, and had received or were referred for ablation every 3 months. The survey comprised 96 questions on physician demographics, AF types, and treatment practices. Overall, 54% of respondents considered guidelines to be the most important nonpatient factor influencing treatment choice. Across most queried comorbidities, amiodarone was selected by 60% to 80% of respondents. Other nonadherent usage included sotalol by 21% in patients with renal impairment; dofetilide initiation (16%, United States only) outside of hospital; class Ic agents by 6% in coronary artery disease; and dronedarone by 8% in patients with heart failure with reduced ejection fraction. Additionally, rhythm control strategies were frequently chosen in asymptomatic AF (antiarrhythmic drugs [AADs], 35%; ablation, 8%) and subclinical AF (AADs, 38%; ablation, 13%). Despite guideline algorithms emphasizing safety first, efficacy (48%) was selected as the most important consideration for AAD choice, followed by safety (34%).Conclusions: Despite surveyed clinicians recognizing the importance of guidelines, nonadherence was frequently observed. While deviation may be reasonable in selected patients, in general, nonadherence has the potential to compromise patient safety. These findings highlight an underappreciation of the safe use of AADs, emphasizing the need for interventions to support optimal AAD selection.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Carlsson, Andreas, 1978-, et al.
(författare)
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The Coaching Behavior Scale for Sport (CBS-S) : A psychometric evaluation of the Swedish version.
- 2016
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 26:1, s. 116-123
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Tidskriftsartikel (refereegranskat)abstract
- The present study validated a Swedish version of the 47-item Coaching Behavior Scale for Sport (CBS-S). Sample 1 consisted of 506 team sport athletes [262 men and 244 women; mean age: 22.20, standard deviation (SD) = 3.90] distributed across 41 coaches at the two highest national levels of various sports. Athletes completed the CBS-S and established questionnaires of coaching behaviors (LSS), self-confidence (CSAI-2R), and coach-athlete relationship (CART-Q). An additional sample of 39 basketball players (21 men and 18 women; mean age = 17.40, SD = 2.39) completed the CBS-S twice, approximately 4 weeks apart. Confirmatory factor analysis showed an acceptable model fit for the seven-factor version of the CBS-S, although two items of the negative personal rapport subscale displayed insufficient factor loadings. Correlations between the subscales of the CBS-S and established instruments were in accordance with theoretical expectations, supporting the concurrent validity. Cronbach's alpha (> 0.82) for all dimensions provided support for the reliability of the CBS-S, and test-retest correlations indicated moderate stability over time. Cultural differences in the assessment of coaching behaviors and the usability of the CBS-S by coaches for self-reflection and development are discussed.
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| 22. |
- Carlsson, Katrin, et al.
(författare)
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Fear and the Amygdala : Manipulation of Awareness Generates Differential Cerebral Responses to Phobic and Fear-Relevant (but Nonfeared) Stimuli
- 2004
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Ingår i: Emotion. - : American Psychological Association (APA). - 1528-3542 .- 1931-1516. ; 4:4, s. 340-353
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Tidskriftsartikel (refereegranskat)abstract
- Rapid response to danger holds an evolutionary advantage. In this positron emission tomography study, phobics were exposed to masked visual stimuli with timings that either allowed awareness or not of either phobic, fear-relevant (e.g., spiders to snake phobics), or neutral images. When the timing did not permit awareness, the amygdala responded to both phobic and fear-relevant stimuli. With time for more elaborate processing, phobic stimuli resulted in an addition of an affective processing network to the amygdala activity, whereas no activity was found in response to fear-relevant stimuli. Also, right prefrontal areas appeared deactivated, comparing aware phobic and fear-relevant conditions. Thus, a shift from top-down control to an affectively driven system optimized for speed was observed in phobic relative to fear-relevant aware processing. (PsycINFO Database Record (c) 2006 APA, all rights reserved) (journal abstract)
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| 23. |
- Chen, Xinsong, et al.
(författare)
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Breast cancer patient-derived whole-tumor cell culture model for efficient drug profiling and treatment response prediction
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 120:1
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer (BC) is a complex disease comprising multiple distinct subtypes with different genetic features and pathological characteristics. Although a large number of antineoplastic compounds have been approved for clinical use, patient-to-patient variability in drug response is frequently observed, highlighting the need for efficient treatment prediction for individualized therapy. Several patient-derived models have been established lately for the prediction of drug response. However, each of these models has its limitations that impede their clinical application. Here, we report that the whole-tumor cell culture (WTC) ex vivo model could be stably established from all breast tumors with a high success rate (98 out of 116), and it could reassemble the parental tumors with the endogenous microenvironment. We observed strong clinical associations and predictive values from the investigation of a broad range of BC therapies with WTCs derived from a patient cohort. The accuracy was further supported by the correlation between WTC-based test results and patients' clinical responses in a separate validation study, where the neoadjuvant treatment regimens of 15 BC patients were mimicked. Collectively, the WTC model allows us to accomplish personalized drug testing within 10 d, even for small-sized tumors, highlighting its potential for individualized BC therapy. Furthermore, coupled with genomic and transcriptomic analyses, WTC-based testing can also help to stratify specific patient groups for assignment into appropriate clinical trials, as well as validate potential biomarkers during drug development.
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| 24. |
- Chen, Ziqing, et al.
(författare)
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Phosphodiesterase 4A confers resistance to PGE2-mediated suppression in CD25(+)/CD54(+) NK cells
- 2021
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Ingår i: EMBO Reports. - : EMBO Press. - 1469-221X .- 1469-3178. ; 22:3
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Tidskriftsartikel (refereegranskat)abstract
- Inadequate persistence of tumor-infiltrating natural killer (NK) cells is associated with poor prognosis in cancer patients. The solid tumor microenvironment is characterized by the presence of immunosuppressive factors, including prostaglandin E2 (PGE2), that limit NK cell persistence. Here, we investigate if the modulation of the cytokine environment in lung cancer with IL-2 or IL-15 renders NK cells resistant to suppression by PGE2. Analyzing Cancer Genome Atlas (TCGA) data, we found that high NK cell gene signatures correlate with significantly improved overall survival in patients with high levels of the prostaglandin E synthase (PTGES). In vitro, IL-15, in contrast to IL-2, enriches for CD25(+)/CD54(+) NK cells with superior mTOR activity and increased expression of the cAMP hydrolyzing enzyme phosphodiesterase 4A (PDE4A). Consequently, this distinct population of NK cells maintains their function in the presence of PGE2 and shows an increased ability to infiltrate lung adenocarcinoma tumors in vitro and in vivo. Thus, strategies to enrich CD25(+)/CD54(+) NK cells for adoptive cell therapy should be considered.
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| 25. |
- Christiansson, Lisa, 1983-
(författare)
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Myeloid-Derived Suppressor Cells and Other Immune Escape Mechanisms in Chronic Leukemia
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic myeloid leukemia (CML) is characterized by the Philadelphia chromosome, a minute chromosome that leads to the creation of the fusion gene BCR/ABL and the transcription of the fusion protein BCR/ABL in transformed cells. The constitutively active tyrosine kinase BCR/ABL confers enhanced proliferation and survival on leukemic cells. CML has in only a few decades gone from being a disease with very bad prognosis to being a disease that can be effectively treated with oral tyrosine kinase inhibitors (TKIs). TKIs are drugs inhibiting BCR/ABL as well as other tyrosine kinases. In this thesis, the focus has been on the immune system of CML patients, on immune escape mechanisms present in untreated patients and on how these are affected by TKI therapy. We have found that newly diagnosed, untreated CML patients exert different kinds of immune escape mechanisms. Patients belonging to the Sokal high-risk group had higher levels of myeloid-derived suppressor cells (MDSCs) as well as high levels of the programmed death receptor 1 (PD-1)-expressing cytotoxic T cells compared to control subjects. Moreover, CML patients had higher levels of myeloid cells expressing the ligand for PD-1, PD-L1. CML patients as well as patients with B cell malignacies had high levels of soluble CD25 in blood plasma. In B cell malignacies, sCD25 was found to be released from T regulatory cells (Tregs). Treatment with the TKIs imatinib or dasatinib decreased the levels of MDSCs in peripheral blood. Tregs on the other hand increased during TKI therapy. The immunostimulatory molecule CD40 as well as NK cells increased during therapy, indicating an immunostimulatory effect of TKIs. When evaluating immune responses, multiplex techniques for quantification of proteins such as cytokines and chemokines are becoming increasingly popular. With these techniques a lot of information can be gained from a small sample volume and complex networks can be more easily studied than when using for example the singleplex ELISA. When comparing different multiplex platforms we found that the absolute protein concentration measured by one platform rarely correlated with the absolute concentration measured by another platform. However, relative quantification was better correlated.
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| 26. |
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| 27. |
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| 28. |
- Dardar, Raghad, et al.
(författare)
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Industrial Experiences of Building a Safety Case in Compliance with ISO 26262
- 2012
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Ingår i: 23RD IEEE INTERNATIONAL SYMPOSIUM ON SOFTWARE RELIABILITY ENGINEERING WORKSHOPS (ISSREW 2012). - 9780769549286 ; , s. 349-354
-
Konferensbidrag (refereegranskat)abstract
- The ISO 26262 functional safety standard provides appropriate development processes, requirements and safety integrity levels specific for the automotive domain. One crucial requirement consists of the creation of a safety case, a structured argument, which inter-relates evidence and claims, needed to show that safety-critical systems are acceptably safe. The standard is currently not mandatory to be applied to safety critical systems installed in heavy trucks; however, this is likely to be changed by 2016. This paper describes the experience gathered by applying the standard to the Fuel Level Estimation and Display System, a subsystem that together with other subsystems plays a significant role in terms of global system safety for heavy trucks manufactured by Scania. More specifically, exploratory and laborious work related to the creation of a safety case in compliance with ISO 26262 in an inexperienced industrial setting is described, and the paper ends with presenting some lessons learned together with guidelines to facilitate the adoption of ISO 26262.
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| 29. |
- de Blanche, Andreas, 1975-, et al.
(författare)
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A methodology for estimating co-scheduling slowdowns due to memory bus contention on multicore nodes
- 2014
-
Ingår i: Proceedings of the IASTED International Conference on Parallel and Distributed Computing and Networks, PDCN 2014. - : ACTA Press. - 9780889869677 - 9780889869653 ; , s. 216-223
-
Konferensbidrag (refereegranskat)abstract
- When two or more programs are co-scheduled on the same multicore computer they might experience a slowdown due to the limited off-chip memory bandwidth. According to our measurements, this slowdown does not depend on the total bandwidth use in a simple way. One thing we observe is that a higher memory bandwidth usage will not always lead to a larger slowdown. This means that relying on bandwidth usage as input to a job scheduler might cause non-optimal scheduling of processes on multicore nodes in clusters, clouds, and grids. To guide scheduling decisions, we instead propose a slowdown based characterization approach. Real slowdowns are complex to measure due to the exponential number of experiments needed. Thus, we present a novel method for estimating the slowdown programs will experience when co-scheduled on the same computer. We evaluate the method by comparing the predictions made with real slowdown data and the often used memory bandwidth based method. This study show that a scheduler relying on slowdown based categorization makes fewer incorrect co-scheduling choices and the negative impact on program execution times is less than when using a bandwidth based categorization method.
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| 30. |
- de Blanche, Andreas
(författare)
-
A Slowdown Prediction Method to Improve Memory Aware Scheduling
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Scientific and technological advances in the area of integrated circuits have allowed the performance of microprocessors to grow exponentially since the late 1960's. However, the imbalance between processor and memory bus capacity has increased in recent years. The increasing on-chip-parallelism of multi-core processors has turned the memory subsystem into a key factor for achieving high performance. When two or more processes share the memory subsystem their execution times typically increase, even at relatively low levels of memory traffic. Current research shows that a throughput increase of up to 40% is possible if the job-scheduler can minimizes the slowdown caused by memory contention in industrial multi-core systems such as high performance clusters, datacenters or clouds. In order to optimize the throughput the job-scheduler has to know how much slower the process will execute when co-scheduled on the same server as other processes. Consequently, unless the slowdown is known, or can be fairly well estimated, the scheduling becomes pure guesswork and the performance suffers. The central question addressed in this thesis is how the slowdown caused by memory traffic interference between processes executing on the same server can be predicted and to what extent. This thesis presents and evaluates a new slowdown prediction method which estimates how much longer a program will execute when co-scheduled on the same multi-core server as another program. The method measures how external memory traffic affects a program by generating different levels of synthetic memory traffic while observing the change in execution time. Based on the observations it makes a first order prediction of how much slowdown the program will experience when exposed to external memory traffic. Experimental results show that the method's predictions correlate well with the real measured slowdowns. Furthermore, it is shown that scheduling based on the new slowdown prediction method yields a higher throughput than three other techniques suggested for avoiding co-scheduling slowdowns caused by memory contention. Finally, a novel scheme is suggested to avoid some of the worst co-schedules, thus increasing the system throughput.
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| 31. |
- de Blanche, Andreas, 1975-, et al.
(författare)
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Addressing characterization methods for memory contention aware co-scheduling
- 2015
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Ingår i: Journal of Supercomputing. - : Springer Science and Business Media LLC. - 0920-8542 .- 1573-0484. ; 71:4, s. 1451-1483
-
Tidskriftsartikel (refereegranskat)abstract
- The ability to precisely predict how memory contention degrades performance when co-scheduling programs is critical for reaching high performance levels in cluster, grid and cloud environments. In this paper we present an overview and compare the performance of state-of-the-art characterization methods for memory aware (co-)scheduling. We evaluate the prediction accuracy and co-scheduling performance of four methods: one slowdown-based, two cache-contention based and one based on memory bandwidth usage. Both our regression analysis and scheduling simulations find that the slowdown based method, represented by Memgen, performs better than the other methods. The linear correlation coefficient (Formula presented.) of Memgen's prediction is 0.890. Memgen's preferred schedules reached 99.53 % of the obtainable performance on average. Also, the memory bandwidth usage method performed almost as well as the slowdown based method. Furthermore, while most prior work promote characterization based on cache miss rate we found it to be on par with random scheduling of programs and highly unreliable.
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| 32. |
- de Blanche, Andreas, 1975-, et al.
(författare)
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Disallowing Same-program Co-schedules to Improve Efficiency in Quad-core Servers
- 2017
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Ingår i: Proceedings of the Joined Workshops COSH 2017 and VisorHPC 2017. - 9783000555640 ; , s. 1-7
-
Konferensbidrag (refereegranskat)abstract
- Programs running on different cores in a multicore server are often forced to share resources like off-chip memory,caches, I/O devices, etc. This resource sharing often leads to degraded performance, a slowdown, for the program sthat share the resources. A job scheduler can improve performance by co-scheduling programs that use different resources on the same server. The most common approachto solve this co-scheduling problem has been to make job schedulers resource aware, finding ways to characterize and quantify a program’s resource usage. We have earlier suggested a simple, program and resource agnostic, scheme as a stepping stone to solving this problem: Avoid Terrible Twins, i.e., avoid co-schedules that contain several instances from the same program. This scheme showed promising results when applied to dual-core servers. In this paper, we extend the analysis and evaluation to also cover quad-core servers. We present a probabilistic model and empirical data that show that execution slowdowns get worse as the number of instances of the same program increases. Our scheduling simulations show that if all co-schedules containing multiple instances of the same program are removed, the average slowdown is decreased from 54% to 46% and that the worst case slowdown is decreased from 173% to 108%.
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| 33. |
- de Blanche, Andreas, 1975-, et al.
(författare)
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Initial Formulation of Why Disallowing Same Program Co-schedules Improves Performance
- 2017. - 1
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Ingår i: Co-Scheduling of HPC Applications. - Netherlands : IOS Press. - 9781614997290 - 9781614997306 ; , s. 95-113
-
Bokkapitel (refereegranskat)abstract
- Co-scheduling processes on different cores in the same server might leadto excessive slowdowns if they use the same shared resource, like a memory bus. Ifpossible, processes with a high shared resource use should be allocated to differentserver nodes to avoid contention, thus avoiding slowdown. This article proposesthe more general principle that twins, i.e. several instances of the same program,should be allocated to different server nodes. The rational for this is that instancesof the same program use the same resources and they are more likely to be eitherlow or high resource users. High resource users should obviously not be combined,but a bit non-intuitively, it is also shown that low resource users should also notbe combined in order to not miss out on better scheduling opportunities. This isverified using both a probabilistic argument as well as experimentally using tenprograms from the NAS parallel benchmark suite running on two different systems.By using the simple rule of forbidding these terrible twins, the average slowdownis shown to decrease from 6.6% down to 5.9% for System A and from 9.5% to8.3% for System B. Furthermore, the worst case slowdown is lowered from 12.7%to 9.0% and 19.5% to 13% for systems A and B, respectively. Thus, indicating aconsiderable improvement despite the rule being program agnostic and having noinformation about any program’s resource usage or slowdown behavior.
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| 34. |
- de Blanche, Andreas, 1975-, et al.
(författare)
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Node Sharing for Increased Throughput and Shorter Runtimes : an Industrial Co-Scheduling Case Study
- 2018
-
Ingår i: Proceedings of the 3rd Workshop on Co-Scheduling of HPC Applications (COSH 2018). ; , s. 15-20
-
Konferensbidrag (refereegranskat)abstract
- The allocation of jobs to nodes and cores in industrial clusters is often based on queue-system standard settings, guesses or perceived fairness between different users and projects. Unfortunately, hard empirical data is often lacking and jobs are scheduled and co-scheduled for no apparent reason. In this case-study, we evaluate the performance impact of co-scheduling jobs using three types of applications and an existing 450+ node cluster at a company doing large-scale parallel industrial simulations. We measure the speedup when co-scheduling two applications together, sharing two nodes, compared to running the applications on separate nodes. Our results and analyses show that by enabling co-scheduling we improve performance in the order of 20% both in throughput and in execution times, and improve the execution times even more if the cluster is running with low utilization. We also find that a simple reconfiguration of the number of threads used in one of the applications can lead to a performance increase of 35-48% showing that there is a potentially large performance increase to gain by changing current practice in industry.
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| 35. |
- de Blanche, Andreas, et al.
(författare)
-
Terrible Twins : A Simple Scheme to Avoid Bad Co-Schedule
- 2016
-
Ingår i: Proceedings of the 1st COSH Workshop on Co-Scheduling of HPC Applications. - Munchen. ; , s. 1-6
-
Konferensbidrag (refereegranskat)abstract
- Co-scheduling processes on different cores in the same server might lead to excessive slowdowns if they use a shared resource,like the memory bus. If possible, processes with a high shared resource use should be allocated to different server nodes to avoid contention, thus avoiding slowdown.This paper introduces the simple scheme of avoiding to coschedule twins, i.e., several instances of the same program.The rational for this is that instances of the same program use the same resources and they are more likely to be either low or high resource users − high resource users should obviously not be combined, but a bit non-intuitively, it is also shown that low resource users should also not be combined in order to not miss out on better scheduling opportunities.This is verified using both a statistical argument as well as experimentally using ten programs from the NAS parallel benchmark suite. By using the simple rule of forbidding twins, the average slowdown is shown to decrease from 6.6% down to 5.9%, and the worst case slowdown is lowered from 12.7% to 9.0%, indicating a considerable improvement despite having no information about any programs' resource usage or slowdown behavior.
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| 36. |
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| 37. |
- Dodig Crnkovic, Gordana, 1955, et al.
(författare)
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Risk-based Decision-making Fallacies: Why Present Functional Safety Standards Are Not Enough
- 2017
-
Ingår i: Software Architecture Workshops (ICSAW), 2017 IEEE International Conference.
-
Konferensbidrag (refereegranskat)abstract
- Functional safety of a system is the part of its overall safety, understood as freedom from unacceptable/unreasonable risks that depends on a system operating correctly in response to its inputs. Functional safety elements are examined at every stage of the software development life cycle, including requirement specification, design, implementation, verification, validation and deployment. Acceptability of risks is judged within a framework of analysis with contextual and cultural aspects by individuals who may introduce subjectivity and misconceptions in the assessment. While functional safety standards elaborate much on the avoidance of unreasonable risk, little is addressed on the issue of avoiding unreasonable judgments of risk. Through the studies of common fallacies in risk perception and ethics, we present a moral-psychological analysis of functional safety standards and propose plausible improvements of the involved risk-related decision making processes, with a focus on the notion of an acceptable residual risk. As a functional safety reference model, we use the functional safety standard ISO 26262, addressing potential hazards caused by malfunctions of hardware and software systems within road vehicles, and defines safety measures that are required to achieve an acceptable level of safety. Analysis points out the critical importance of a robust safety culture with developed countermeasures to the common fallacies in risk perception, which are not addressed by contemporary functional safety standards. We argue that functional safety standards should be complemented with the analysis of potential hazards caused by fallacies in risk perception, their countermeasures, and the requirement that residual risks must be explicated, motivated, and accompanied by a plan for their continuous reduction. This approach becomes especially important in contemporary developed autonomous vehicles with increasing computational applications.
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| 38. |
- Dolby, Viveka, et al.
(författare)
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Effects of pH, salt and time on ligand binding properties of overexpressed melanocortin 4 receptor.
- 2004
-
Ingår i: Journal of Biochemical and Biophysical Methods. - : Elsevier BV. - 0165-022X. ; 58:3, s. 195-205
-
Tidskriftsartikel (refereegranskat)abstract
- The G-protein coupled melanocortin 4 receptor (MC4r) plays an important role in the energy metabolism. We overexpressed the MC4r in CHO cells and performed characterisation studies on the cell membranes to determine functional stability and ligand binding properties of the receptor. The affinity for the ligands [Nle4, Image-Phe7]-αMSH and MTII was lost below pH 6 but could be restored by returning to physiological pH. Increasing NaCl concentration up to 1 M had little influence on the binding of either ligand. At neutral pH, physiological salt concentration and 4 °C the ligand affinity of the receptor was stable for up to 6 days. These findings will facilitate design of purification methods for the receptor.
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| 39. |
- du Bois, Andreas, et al.
(författare)
-
Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in first-line treatment of epithelial ovarian cancer.
- 2010
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Ingår i: Journal of Clinical Oncology. - : American society of clinical oncology. - 0732-183X .- 1527-7755. ; 28:27, s. 4162-4169
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: One attempt to improve long-term survival in patients with advanced ovarian cancer was thought to be the addition of more non-cross-resistant drugs to platinum-paclitaxel combination regimens. Gemcitabine was among the candidates for a third drug.PATIENTS AND METHODS: We performed a prospective, randomized, phase III, intergroup trial to compare carboplatin plus paclitaxel (TC; area under the curve [AUC] 5 and 175 mg/m(2), respectively) with the same combination and additional gemcitabine 800 mg/m(2) on days 1 and 8 (TCG) in previously untreated patients with advanced epithelial ovarian cancer. TC was administered intravenously (IV) on day 1 every 21 days for a planned minimum of six courses. Gemcitabine was administered by IV on days 1 and 8 of each cycle in the TCG arm.RESULTS: Between 2002 and 2004, 1,742 patients were randomly assigned; 882 and 860 patients received TC and TCG, respectively. Grades 3 to 4 hematologic toxicity and fatigue occurred more frequently in the TCG arm. Accordingly, quality-of-life analysis during chemotherapy showed a disadvantage in the TCG arm. Although objective response was slightly higher in the TCG arm, this did not translate into improved progression-free survival (PFS) or overall survival (OS). Median PFS was 17.8 months for the TCG arm and 19.3 months for the TC arm (hazard ratio [HR], 1.18; 95% CI, 1.06 to 1.32; P = .0044). Median OS was 49.5 for the TCG arm and 51.5 months for the TC arm (HR, 1.05; 95% CI, 0.91 to 1.20; P = .5106).CONCLUSION: The addition of gemcitabine to carboplatin plus paclitaxel increased treatment burden, reduced PFS time, and did not improve OS in patients with advanced epithelial ovarian cancer. Therefore, we recommend no additional clinical use of TCG in this population.
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| 40. |
- Ferm, Lisa, 1980-, et al.
(författare)
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Defender, Disturber or Driver? The ideal-typical professional identities of HR practitioners
- 2023
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Ingår i: Personnel review. - : EMERALD GROUP PUBLISHING LTD. - 0048-3486 .- 1758-6933.
-
Tidskriftsartikel (refereegranskat)abstract
- PurposeThis study aims to contribute knowledge about different professional identities represented among HR practitioners from Webers "ideal types" framework.Design/methodology/approachThe paper is based on semi-structured interviews with 34 Swedish HR practitioners working in large public and private organisations.FindingsThe findings reveal that HR practitioners identity is perceived as indistinct, unclear and shattered, which leaves lots of room for interpreting HR identity. Based on a thematic content analysis, three different ideal-type identities are presented, each representing the characteristic traits of an HR identity type. These are the Defender who always supports the managers, the Disturber who questions the managers in favour of the employees and the Driver who focuses on the economic expansion of the organisation.Research limitations/implicationsOne of the potential constraints of this study is the authors reliance on interview data. This finding implies that future research can employ mixed methods or observational techniques to bridge the gap between narrated responsibilities and real-time actions. The data source, predominantly from larger organisations, presents another limitation. This raises a significant research implication: there is a need to study identity formation among HR practitioners in smaller organisations. The theoretical framework this study contributes can aid in comprehending HR practitioners identities and their corresponding actions. Continued research might explore the significance of these ideal-type identities.Practical implicationsThe model presented provides a new way of understanding HR practitioners complex and shattered professional identity and the various stakeholders that direct different expectations towards them. This knowledge can be used both in HR education and in HR work as a basis for discussing the social work environment of HR practitioners and negotiating their work and identity.Originality/valueThe study contributes knowledge of the professional identities of HR managers, an under-researched area, especially when it comes to empirical research about the HR practitioners own experiences of their everyday work and view of the HR profession.
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| 41. |
- Forsberg, Håkan, et al.
(författare)
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Assurance Strategy for New Computing Platforms in Safety-Critical Avionics
- 2019
-
Ingår i: Aerospace Technology Congress 2019 FT2019. - Stockholm, Sweden : Linköping University Electronic Press. - 9789175190068 ; , s. 137-144
-
Konferensbidrag (refereegranskat)abstract
- An assurance strategy for new computing platforms in safety-critical avionics has to be flexible and take into account different types of commercial-of-the-shelf (COTS) hardware technologies. Completely new COTS technologies are already being introduced and successfully used in other domains. Good examples are heterogeneous platforms, hardware-based machine learning and approximate computing. Current avionics certification guidance material cannot cope with next generation of devices. We suggest using the generic assurance approach of the Overarching Properties (OPs) together with assurance cases to argument that COTS assurance objectives are met and to achieve the flexibility required for future computing platforms. We introduce a novel assurance cased-based OP approach in [1] and refine the work into a framework in [2]. Within this framework we are able to integrate COTS technology specific assurance objectives using a five-step process. In this paper, we show through some representative examples of emerging computing platforms that our strategy is a way forward for new platforms in safety-critical avionics.
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| 42. |
- Galon, Jerome, et al.
(författare)
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Cancer classification using the Immunoscore : a worldwide task force
- 2012
-
Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 10, s. 205-
-
Forskningsöversikt (refereegranskat)abstract
- Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N) and evidence for metastases (M). However, it is now recognized that clinical outcome can significantly vary among patients within the same stage. The current classification provides limited prognostic information, and does not predict response to therapy. Recent literature has alluded to the importance of the host immune system in controlling tumor progression. Thus, evidence supports the notion to include immunological biomarkers, implemented as a tool for the prediction of prognosis and response to therapy. Accumulating data, collected from large cohorts of human cancers, has demonstrated the impact of immune-classification, which has a prognostic value that may add to the significance of the AJCC/UICC TNM-classification. It is therefore imperative to begin to incorporate the ` Immunoscore' into traditional classification, thus providing an essential prognostic and potentially predictive tool. Introduction of this parameter as a biomarker to classify cancers, as part of routine diagnostic and prognostic assessment of tumors, will facilitate clinical decision-making including rational stratification of patient treatment. Equally, the inherent complexity of quantitative immunohistochemistry, in conjunction with protocol variation across laboratories, analysis of different immune cell types, inconsistent region selection criteria, and variable ways to quantify immune infiltration, all underline the urgent requirement to reach assay harmonization. In an effort to promote the Immunoscore in routine clinical settings, an international task force was initiated. This review represents a follow-up of the announcement of this initiative, and of the J Transl Med. editorial from January 2012. Immunophenotyping of tumors may provide crucial novel prognostic information. The results of this international validation may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).
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| 43. |
- Gerhardsson, Andreas, 1984-
(författare)
-
Processing affective information after sleep loss
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is not fully understood why we need to sleep, although it is evident that sleep loss has consequences for many emotional and cognitive functions. The last couple of decades, sleep researchers have been increasingly devoted to better understand the relationship between sleep and affect. However, it is still poorly understood how sleep deprivation influences the way in which affective information is processed. The aim of this thesis was to investigate if there is a bias towards affective information after sleep deprivation and whether such bias influence information processing.Study I tested reinforcement learning from positive as compared to negative feedback after two nights of sleep restriction. There were no indications of the expected reward-seeking behavior in generalized learning or in the learning strategy. A slowing in learning rate inferred from computational modeling was observed primarily for negative feedback. This could be indicative of a slowing in memory integration. It is unclear if the dopamine alterations proposed to cause reward-seeking behavior after total sleep deprivation are also implicated after sleep restriction.Study II examined the neurophysiological response of the competition of attention between unpleasant and neutral pictures after two nights of sleep restriction. We found no alterations of sleep restriction on attention in relation to picture valence, or on executive control of attention. Despite observations of an increased sleepiness, an impaired sustained attention, and reduced positive affect, the few hours of allowed sleep may have been enough to counteract an affective bias and an executive control impairment.Study III tested if one night of total sleep deprivation altered working memory for positive, negative, or neutral pictures using two levels of working memory load. Results showed that working memory accuracy was generally impaired after sleep deprivation, independent of picture valence. However, in the sleep deprived group we observed faster responses to positive and slower responses to negative pictures. These results could indicate a bias towards both positive and negative pictures, but with opposite consequences on working memory speed.Study IV used the same protocol as Study III to combinedly test two common findings among older adults: That they prioritize positive over negative stimuli (the positivity effect), and that they are less affected by sleep deprivation. Working memory performance was overall better for positive than negative pictures, with no differences between the sleep conditions. This positivity effect was only present in the low working memory load condition. These results show that even after a state-dependent challenge such as sleep deprivation, the positivity effect remains in older adults, at least when working memory load is low.Overall, the Studies in this thesis demonstrate signs of affective bias as well as lack thereof after total and partial sleep deprivation. The use of a diverse set of tasks and methodology may have contributed to the discrepancies in the findings, but it also highlights that we have yet to fully understand how lack of sleep may influence the processing of affectively valuable information.
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| 44. |
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| 45. |
- Ginks, Matthew R., et al.
(författare)
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Relationship between intracardiac impedance and left ventricular contractility in patients undergoing cardiac resynchronization therapy
- 2011
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 13:7, s. 984-991
-
Tidskriftsartikel (refereegranskat)abstract
- Aims Cardiac resynchronization therapy (CRT) has dramatically improved the symptoms and prognosis of patients with heart failure in large randomized clinical trials. Optimization of device settings may maximize benefit on an individual basis, although the best method for this is not yet established. We evaluated the use of cardiogenic impedance measurements (derived from intracardiac impedance signals) in CRT device optimization, using invasive left ventricular (LV) dP/dt(max) as the reference. Methods and results Seventeen patients underwent invasive haemodynamic assessment using a pressure wire placed in the LV cavity at the time of CRT device implantation. Intracardiac impedance measurements were made at different atrioventricular (AV) and interventricular (VV) delays and compared with LV dP/dt(max). We assessed the performance of patient-specific and generic impedance-based models in predicting acute haemodynamic response to CRT. In two patients, LV catheterization with the pressure wire was unsuccessful and in two patients LV lead delivery was unsuccessful; therefore, data were acquired for 13 out of 17 patients. Left ventricular dP/dt(max) was 919 +/- 182 mmHg/s at baseline and this increased acutely (by 24%) to 1121 +/- 226 mmHg/s as a result of CRT. The patient-specific impedance-based model correctly predicted the optimal haemodynamic response (to within 5% points) for AV and VV delays in 90 and 92% of patients, respectively. Conclusion Cardiogenic impedance measurements are capable of correctly identifying the maximum achievable LV dP/dt(max) as measured by invasive haemodynamic assessment. This study suggests that cardiogenic impedance can potentially be used for CRT optimization and may have a role in ambulatory assessment of haemodynamics.
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| 46. |
- Gottschalk, Ingo, et al.
(författare)
-
Conversion between two cytochalasin B-binding states of the human GLUT1 glucose transporter
- 2000
-
Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 267:23, s. 6875-6882
-
Tidskriftsartikel (refereegranskat)abstract
- Two cytochalasin B-binding states of the human red blood cell facilitative glucose transporter GLUT1 were studied, one exhibiting one cytochalasin B-binding site on every second GLUT1 monomer (state 1) and the other showing one site per monomer (state 2). Quantitative affinity chromatography of cytochalasin B was performed on (a) biotinylated red blood cells, (b) cytoskeleton-depleted red blood cell membrane vesicles, and (c) GLUT1 proteoliposomes. The cells were adsorbed on streptavidin-derivatized gel beads, and the vesicles and proteoliposomes entrapped in dextran-grafted agarose gel beads. Cytochalasin B binding to free vesicles and proteoliposomes was analyzed by Hummel and Dreyer size-exclusion chromatography and ultracentrifugation. Analysis of the biotinylated cells indicated an equilibrium between the two GLUT1 states. GLUT1 in free membrane vesicles attained state 2, but was converted into state 1 on entrapment of the vesicles. Purification of GLUT1 in the presence of non-ionic detergent followed by reconstitution produced GLUT1 in state 1. This state was maintained after entrapment of the proteoliposomes. Finally, GLUT1 showed slightly higher affinity for cytochalasin B in state 1 than in state 2. In summary, the cytochalasin B-binding state of GLUT1 seemed to be affected by (a) biotinylation of the cell surface, (b) removal of the cytoskeleton at high pH and low ionic strength, (c) interaction between the dextran-grafted agarose gel matrix and the membrane vesicles, and (d) reconstitution to form proteoliposomes.
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| 47. |
- Gottschalk, Ingo, et al.
(författare)
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Immobilised biomembrane affinity chromatography for binding studies of membrane proteins
- 2002
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Ingår i: Journal of chromatography. B. - 1570-0232 .- 1873-376X. ; 768:1, s. 31-40
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Forskningsöversikt (refereegranskat)abstract
- Analyses of specific interactions between solutes and a membrane protein can serve to characterize the protein. Frontal affinity chromatography of an interactant on a column containing the membrane protein immobilized in a lipid environment is a simple and robust approach for series of experiments with particular protein molecules. Regression analysis of the retention volumes at a series of interactant concentrations shows the affinity of the protein for the interactant and the amount of active binding sites. The higher the affinity, the fewer sites are required to give sufficient retention. Competition experiments provide the affinities of even weakly binding solutes and the non-specific retention of the primary interactant. Hummel and Dreyer size-exclusion chromatography allows complementary analyses of non-immobilized membrane materials. Analyses of the human facilitative glucose transporter GLUT1 by use of the inhibitor cytochalasin B (radioactively labeled) and the competitive substrate D-glucose (non-labeled) showed that GLUT1 interconverted between two states, exhibiting one or two cytochalasin B-binding sites per two GLUTI monomers, dependent on the membrane composition and environment. Similar analyses of a nucleoside transporter, a photosynthetic reaction center, nicotinic acetylcholine receptors and a P-glycoprotein, alternative techniques, and immobilized-liposome chromatographic approaches are presented briefly.
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| 48. |
- Götherström, Cecilia, et al.
(författare)
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Fetal and adult multipotent mesenchymal stromal cells are killed by different pathways
- 2011
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Ingår i: Cytotherapy. - : Elsevier BV. - 1465-3249 .- 1477-2566. ; 13:3, s. 269-278
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Tidskriftsartikel (refereegranskat)abstract
- Background aims. Multipotent mesenchymal stromal cells, also known as mesenchymal stem cells (MSC), can be isolated from adult and fetal tissues. Recently, there has been considerable interest in MSC because they have features favorable for transplantation, namely their multipotency and non-immunogenic properties. Methods. We analyzed how human MSC derived from first-trimester fetal liver and adult bone marrow interact with naive and activated innate natural killer (NK) cells. NK cell function was studied by measuring killing of MSC, as well as degranulation (CD107a) induced by MSC. To assess the importance of NK cell killing, expression of surface epitopes was analyzed by flow cytometry on MSC before and after stimulation with interferon (IFN)gamma gamma. Results. Fetal and adult MSC express several ligands to activating NK cell receptors as well as low levels of HLA class I, with large inter-individual variation. Naive peripheral blood NK cells did not lyse fetal or adult MSC, whereas interleukin (IL)2 activated allogeneic as well as autologous NK cells did. Pre-incubation of MSC with IFN-gamma gamma increased their levels of HLA class I, protecting them from NK cell recognition. Fetal and adult MSC were preferably killed via the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) pathways, respectively. Blocking NKG2D reduced NK cell degranulation in both fetal and adult MSC. Conclusions. Fetal and adult MSC differ in their interactions with NK cells. Both fetal and adult MSC are susceptible to lysis by activated NK cells, which may have implications for the use of MSC in cell therapy.
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| 49. |
- Hanning, Andreas, 1982, et al.
(författare)
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Are we educating engineers for sustainability? Comparison between obtained competences and Swedish industry's needs
- 2012
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Ingår i: International Journal of Sustainability in Higher Education. - : Emerald. - 1467-6370. ; 13:3, s. 305-320
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Tidskriftsartikel (refereegranskat)abstract
- Purpose – The aim of this study is to contribute to the quality improvement and long-term strategic development of education for sustainable development (ESD) in engineering education curricula.Design/methodology/approach – The content in 70 courses in environment and SD were characterized and quantified using course document text analysis. Additionally, two questionnaires were sent to students and alumni at Chalmers, and interviews and focus group discussions were conducted with representatives from 16 Swedish companies and five organizations.Findings – It was found that industry demands a broader range of competences in SD amongst engineers in general than what is currently provided. In total, 35 per cent of alumni claim they encounter sustainability issues from sometimes to daily in their work. However, only half of them believe they possess enough competences to make decisions from a sustainability perspective. Quantity, coverage and the level of integration in the educational programme all appear to be important for the students' perceived competences on SD and for the importance that they put on achieving SD.Originality/value – Earlier research has reported on how to further develop the idea and design of ESD and on competence needs in general. Few attempts have been made to assess industry's needs of competences in SD. This paper sheds light on how engineering universities educate for SD and benchmarks this to industry's needs in an exploratory case study, using Chalmers as an example.
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| 50. |
- He, Xingkang, et al.
(författare)
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Visualization of human T lymphocyte-mediated eradication of cancer cells in vivo
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 117:37, s. 22910-22919
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Tidskriftsartikel (refereegranskat)abstract
- Lymphocyte-based immunotherapy has emerged as a break-through in cancer therapy for both hematologic and solid malignancies. In a subpopulation of cancer patients, this powerful therapeutic modality converts malignancy to clinically manageable disease. However, the T cell- and chimeric antigen receptor T (CAR-T) cell-mediated antimetastatic activity, especially their impacts on microscopic metastatic lesions, has not yet been investigated. Here we report a living zebrafish model that allows us to visualize the metastatic cancer cell killing effect by tumor- infiltrating lymphocytes (TILs) and CAR-T cells in vivo at the single-cell level. In a freshly isolated primary human melanoma, specific TILs effectively eliminated metastatic cancer cells in the living body. This potent metastasis-eradicating effect was validated using a human lymphoma model with CAR-T cells. Furthermore, cancer-associated fibroblasts protected metastatic cancer cells from T cell-mediated killing. Our data provide an in vivo platform to validate antimetastatic effects by human T cell-mediated immunotherapy. This unique technology may serve as a precision medicine platform for assessing anticancer effects of cellular immunotherapy in vivo before administration to human cancer patients.
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