| 1. |
- Aad, G., et al.
(author)
-
- 2015
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In: Journal of High Energy Physics. - : Springer-Verlag New York. - 1029-8479 .- 1126-6708. ; :5
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Journal article (peer-reviewed)
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| 2. |
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- 2018
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:1
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Research review (peer-reviewed)
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| 3. |
- Bombarda, F., et al.
(author)
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Runaway electron beam control
- 2019
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In: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Journal article (peer-reviewed)
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| 4. |
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| 5. |
- Stroth, U., et al.
(author)
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Progress from ASDEX Upgrade experiments in preparing the physics basis of ITER operation and DEMO scenario development
- 2022
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 62:4
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Journal article (peer-reviewed)abstract
- An overview of recent results obtained at the tokamak ASDEX Upgrade (AUG) is given. A work flow for predictive profile modelling of AUG discharges was established which is able to reproduce experimental H-mode plasma profiles based on engineering parameters only. In the plasma center, theoretical predictions on plasma current redistribution by a dynamo effect were confirmed experimentally. For core transport, the stabilizing effect of fast ion distributions on turbulent transport is shown to be important to explain the core isotope effect and improves the description of hollow low-Z impurity profiles. The L-H power threshold of hydrogen plasmas is not affected by small helium admixtures and it increases continuously from the deuterium to the hydrogen level when the hydrogen concentration is raised from 0 to 100%. One focus of recent campaigns was the search for a fusion relevant integrated plasma scenario without large edge localised modes (ELMs). Results from six different ELM-free confinement regimes are compared with respect to reactor relevance: ELM suppression by magnetic perturbation coils could be attributed to toroidally asymmetric turbulent fluctuations in the vicinity of the separatrix. Stable improved confinement mode plasma phases with a detached inner divertor were obtained using a feedback control of the plasma β. The enhanced D α H-mode regime was extended to higher heating power by feedback controlled radiative cooling with argon. The quasi-coherent exhaust regime was developed into an integrated scenario at high heating power and energy confinement, with a detached divertor and without large ELMs. Small ELMs close to the separatrix lead to peeling-ballooning stability and quasi continuous power exhaust. Helium beam density fluctuation measurements confirm that transport close to the separatrix is important to achieve the different ELM-free regimes. Based on separatrix plasma parameters and interchange-drift-Alfvén turbulence, an analytic model was derived that reproduces the experimentally found important operational boundaries of the density limit and between L- and H-mode confinement. Feedback control for the X-point radiator (XPR) position was established as an important element for divertor detachment control. Stable and detached ELM-free phases with H-mode confinement quality were obtained when the XPR was moved 10 cm above the X-point. Investigations of the plasma in the future flexible snow-flake divertor of AUG by means of first SOLPS-ITER simulations with drifts activated predict beneficial detachment properties and the activation of an additional strike point by the drifts.
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| 6. |
- Meyer, H.F., et al.
(author)
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Overview of physics studies on ASDEX Upgrade
- 2019
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Research review (peer-reviewed)abstract
- The ASDEX Upgrade (AUG) programme, jointly run with the EUROfusion MST1 task force, continues to significantly enhance the physics base of ITER and DEMO. Here, the full tungsten wall is a key asset for extrapolating to future devices. The high overall heating power, flexible heating mix and comprehensive diagnostic set allows studies ranging from mimicking the scrape-off-layer and divertor conditions of ITER and DEMO at high density to fully non-inductive operation (q 95 = 5.5, ) at low density. Higher installed electron cyclotron resonance heating power 6 MW, new diagnostics and improved analysis techniques have further enhanced the capabilities of AUG. Stable high-density H-modes with MW m-1 with fully detached strike-points have been demonstrated. The ballooning instability close to the separatrix has been identified as a potential cause leading to the H-mode density limit and is also found to play an important role for the access to small edge-localized modes (ELMs). Density limit disruptions have been successfully avoided using a path-oriented approach to disruption handling and progress has been made in understanding the dissipation and avoidance of runaway electron beams. ELM suppression with resonant magnetic perturbations is now routinely achieved reaching transiently . This gives new insight into the field penetration physics, in particular with respect to plasma flows. Modelling agrees well with plasma response measurements and a helically localised ballooning structure observed prior to the ELM is evidence for the changed edge stability due to the magnetic perturbations. The impact of 3D perturbations on heat load patterns and fast-ion losses have been further elaborated. Progress has also been made in understanding the ELM cycle itself. Here, new fast measurements of and E r allow for inter ELM transport analysis confirming that E r is dominated by the diamagnetic term even for fast timescales. New analysis techniques allow detailed comparison of the ELM crash and are in good agreement with nonlinear MHD modelling. The observation of accelerated ions during the ELM crash can be seen as evidence for the reconnection during the ELM. As type-I ELMs (even mitigated) are likely not a viable operational regime in DEMO studies of 'natural' no ELM regimes have been extended. Stable I-modes up to have been characterised using -feedback. Core physics has been advanced by more detailed characterisation of the turbulence with new measurements such as the eddy tilt angle - measured for the first time - or the cross-phase angle of and fluctuations. These new data put strong constraints on gyro-kinetic turbulence modelling. In addition, carefully executed studies in different main species (H, D and He) and with different heating mixes highlight the importance of the collisional energy exchange for interpreting energy confinement. A new regime with a hollow profile now gives access to regimes mimicking aspects of burning plasma conditions and lead to nonlinear interactions of energetic particle modes despite the sub-Alfvénic beam energy. This will help to validate the fast-ion codes for predicting ITER and DEMO.
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| 7. |
- Meyer, H., et al.
(author)
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Overview of progress in European medium sized tokamaks towards an integrated plasma-edge/wall solution
- 2017
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In: Nuclear Fusion. - : Institute of Physics Publishing (IOPP). - 0029-5515 .- 1741-4326. ; 57:10
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Journal article (peer-reviewed)abstract
- Integrating the plasma core performance with an edge and scrape-off layer (SOL) that leads to tolerable heat and particle loads on the wall is a major challenge. The new European medium size tokamak task force (EU-MST) coordinates research on ASDEX Upgrade (AUG), MAST and TCV. This multi-machine approach within EU-MST, covering a wide parameter range, is instrumental to progress in the field, as ITER and DEMO core/pedestal and SOL parameters are not achievable simultaneously in present day devices. A two prong approach is adopted. On the one hand, scenarios with tolerable transient heat and particle loads, including active edge localised mode (ELM) control are developed. On the other hand, divertor solutions including advanced magnetic configurations are studied. Considerable progress has been made on both approaches, in particular in the fields of: ELM control with resonant magnetic perturbations (RMP), small ELM regimes, detachment onset and control, as well as filamentary scrape-off-layer transport. For example full ELM suppression has now been achieved on AUG at low collisionality with n = 2 RMP maintaining good confinement H-H(98,H-y2) approximate to 0.95. Advances have been made with respect to detachment onset and control. Studies in advanced divertor configurations (Snowflake, Super-X and X-point target divertor) shed new light on SOL physics. Cross field filamentary transport has been characterised in a wide parameter regime on AUG, MAST and TCV progressing the theoretical and experimental understanding crucial for predicting first wall loads in ITER and DEMO. Conditions in the SOL also play a crucial role for ELM stability and access to small ELM regimes.
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| 8. |
- Meyer, H., et al.
(author)
-
Overview of progress in European medium sized tokamaks towards an integrated plasma-edge/wall solution
- 2017
-
In: Nuclear Fusion. - : Institute of Physics Publishing (IOPP). - 0029-5515 .- 1741-4326. ; 57:10
-
Journal article (peer-reviewed)abstract
- Integrating the plasma core performance with an edge and scrape-off layer (SOL) that leads to tolerable heat and particle loads on the wall is a major challenge. The new European medium size tokamak task force (EU-MST) coordinates research on ASDEX Upgrade (AUG), MAST and TCV. This multi-machine approach within EU-MST, covering a wide parameter range, is instrumental to progress in the field, as ITER and DEMO core/pedestal and SOL parameters are not achievable simultaneously in present day devices. A two prong approach is adopted. On the one hand, scenarios with tolerable transient heat and particle loads, including active edge localised mode (ELM) control are developed. On the other hand, divertor solutions including advanced magnetic configurations are studied. Considerable progress has been made on both approaches, in particular in the fields of: ELM control with resonant magnetic perturbations (RMP), small ELM regimes, detachment onset and control, as well as filamentary scrape-off-layer transport. For example full ELM suppression has now been achieved on AUG at low collisionality with n = 2 RMP maintaining good confinement H-H(98,H-y2) approximate to 0.95. Advances have been made with respect to detachment onset and control. Studies in advanced divertor configurations (Snowflake, Super-X and X-point target divertor) shed new light on SOL physics. Cross field filamentary transport has been characterised in a wide parameter regime on AUG, MAST and TCV progressing the theoretical and experimental understanding crucial for predicting first wall loads in ITER and DEMO. Conditions in the SOL also play a crucial role for ELM stability and access to small ELM regimes.
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| 9. |
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| 10. |
- Abe, O, et al.
(author)
-
Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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In: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Journal article (peer-reviewed)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 11. |
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| 12. |
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| 13. |
- Podadera, I., et al.
(author)
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COMMISSIONING PLAN OF THE IFMIF-DONES ACCELERATOR
- 2022
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In: LINAC 2022 - International Linear Accelerator Conference, Proceedings. - 2226-0366. - 9783954502158 ; , s. 331-334
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Conference paper (peer-reviewed)abstract
- IFMIF-DONES (International Fusion Materials Irradiation Facility- DEMO-Oriented Neutron Early Source) - a powerful neutron irradiation facility for studies and certification of materials to be used in fusion reactors - is planned as part of the European roadmap to fusion electricity. Its main goal will be to characterize and to qualify materials under irradiation in a neutron field similar to the one faced in a fusion reactor. The intense neutron source is produced by impinging deuterons, from high-power linear deuteron accelerator, on a liquid lithium curtain. The facility has accomplished the preliminary design phase and is currently in its detailed design phase. At the present stage, it is important to have a clear understanding of how the commissioning of the facility will be performed, especially the commissioning of a 5 MW CW deuteron beam, together with the lithium curtain and the beam optimization for the neutron irradiation. In this contribution, the present plans for the hardware and beam commissioning of the accelerator will be given, focusing on the most critical aspects of the tiered approach and on the integration of the procedure with the lithium and test systems.
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| 14. |
- Back, A., et al.
(author)
-
Complexity metric based on fraction of penumbra dose - initial study
- 2017
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In: 9TH INTERNATIONAL CONFERENCE ON 3D RADIATION DOSIMETRY ; Journal of Physics Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596.
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Book chapter (other academic/artistic)abstract
- Volumetric modulated arc therapy improve radiotherapy outcome for many patients compared to conventional three dimensional conformal radiotherapy but require a more extensive, most often measurement based, quality assurance. Multi leaf collimator (MLC) aperture-based complexity metrics have been suggested to be used to distinguish complex treatment plans unsuitable for treatment without time consuming measurements. This study introduce a spatially resolved complexity score that correlate to the fraction of penumbra dose and will give information on the spatial distribution and the clinical relevance of the calculated complexity. The complexity metric is described and an initial study on the correlation between the complexity score and the difference between measured and calculated dose for 30 MLC openings is presented. The result of an analysis of the complexity scores were found to correlate to differences between measurements and calculations with a Pearson's r-value of 0.97.
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| 15. |
- Cadrin-Tourigny, Julia, et al.
(author)
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A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy
- 2019
-
In: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 40:23, s. 1850-1858
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Journal article (peer-reviewed)abstract
- AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).
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| 16. |
- Cadrin-Tourigny, Julia, et al.
(author)
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A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy
- 2022
-
In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 43:32, s. 1-9
-
Journal article (peer-reviewed)abstract
- Aims: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. Methods and results: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: Age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P < 0.001). Conclusion: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).
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| 17. |
- Cadrin-Tourigny, Julia, et al.
(author)
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Sudden Cardiac Death Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy : A Multinational Collaboration
- 2021
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In: Circulation: Arrhythmia and Electrophysiology. - : Lippincott Williams & Wilkins. - 1941-3149 .- 1941-3084. ; 14:1
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Journal article (peer-reviewed)abstract
- Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients with ARVC. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD. Methods: We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 prespecified clinical predictors with LTVA (SCD, aborted SCD, sustained, or implantable cardioverter-defibrillator treated ventricular tachycardia >250 beats per minute) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable, or implantable cardioverter-defibrillator treated ventricular tachycardia; or aborted SCD), syncope, 24-hour premature ventricular complexes count, the number of anterior and inferior leads with T-wave inversion, left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping. Results: A total of 864 patients with definite ARVC (40±16 years; 53% male) were included. Over 5.75 years (interquartile range, 2.77-10.58) of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 prespecified clinical predictors, only 4 (younger age, male sex, premature ventricular complex count, and number of leads with T-wave inversion) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (P=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI, 0.69-0.80) and calibration slope of 0.95 (95% CI, 0.94-0.98) indicating minimal over-optimism. Conclusions: LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events.
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| 18. |
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| 19. |
- Dainiak, N, et al.
(author)
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First global consensus for evidence-based management of the hematopoietic syndrome resulting from exposure to ionizing radiation
- 2011
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In: Disaster medicine and public health preparedness. - : Cambridge University Press (CUP). - 1938-744X .- 1935-7893. ; 5:3, s. 202-212
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Journal article (peer-reviewed)abstract
- Objective:Hematopoietic syndrome (HS) is a clinical diagnosis assigned to people who present with ≥1 new-onset cytopenias in the setting of acute radiation exposure. The World Health Organization convened a panel of experts to evaluate the evidence and develop recommendations for medical countermeasures for the management of HS in a hypothetical scenario involving the hospitalization of 100 to 200 individuals exposed to radiation. The objective of this consultancy was to develop recommendations for treatment of the HS based upon the quality of evidence.Methods:English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to panel members before the meeting and updated during the meeting. Published case series and case reports of individuals with HS, published randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation (GRADE) system. In cases in which data were limited or incomplete, a narrative review of the observations was made. No randomized controlled trials of medical countermeasures have been completed for individuals with radiation-associated HS. The use of GRADE analysis of countermeasures for injury to hematopoietic tissue was restricted by the lack of comparator groups in humans. Reliance on data generated in nonirradiated humans and experimental animals was necessary.Results:Based upon GRADE analysis and narrative review, a strong recommendation was made for the administration of granulocyte colony-stimulating factor or granulocyte macrophage colony-stimulating factor and a weak recommendation was made for the use of erythropoiesis-stimulating agents or hematopoietic stem cell transplantation.Conclusions:Assessment of therapeutic interventions for HS in humans exposed to nontherapeutic radiation is difficult because of the limits of the evidence.(Disaster Med Public Health Preparedness. 2011;5:202-212)
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| 20. |
- Dainiak, N, et al.
(author)
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Literature review and global consensus on management of acute radiation syndrome affecting nonhematopoietic organ systems
- 2011
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In: Disaster medicine and public health preparedness. - : Cambridge University Press (CUP). - 1938-744X .- 1935-7893. ; 5:3, s. 183-201
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Journal article (peer-reviewed)abstract
- Objectives:The World Health Organization convened a panel of experts to rank the evidence for medical countermeasures for management of acute radiation syndrome (ARS) in a hypothetical scenario involving the hospitalization of 100 to 200 victims. The goal of this panel was to achieve consensus on optimal management of ARS affecting nonhematopoietic organ systems based upon evidence in the published literature.Methods:English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to conferees in advance of and updated during the meeting. Published case series and case reports of ARS, publications of randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation system. In cases in which data were limited or incomplete, a narrative review of the observations was made.Results:No randomized controlled trials of medical countermeasures have been completed for individuals with ARS. Reports of countermeasures were often incompletely described, making it necessary to rely on data generated in nonirradiated humans and in experimental animals. A strong recommendation is made for the administration of a serotonin-receptor antagonist prophylactically when the suspected exposure is >2 Gy and topical steroids, antibiotics, and antihistamines for radiation burns, ulcers, or blisters; excision and grafting of radiation ulcers or necrosis with intractable pain; provision of supportive care to individuals with neurovascular syndrome; and administration of electrolyte replacement therapy and sedatives to individuals with significant burns, hypovolemia, and/or shock. A strong recommendation is made against the use of systemic steroids in the absence of a specific indication. A weak recommendation is made for the use of fluoroquinolones, bowel decontamination, loperamide, and enteral nutrition, and for selective oropharyngeal/digestive decontamination, blood glucose maintenance, and stress ulcer prophylaxis in critically ill patients.Conclusions:High-quality studies of therapeutic interventions in humans exposed to nontherapeutic radiation are not available, and because of ethical concerns regarding the conduct of controlled studies in humans, such studies are unlikely to emerge in the near future.(Disaster Med Public Health Preparedness. 2011;5:183–201)
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| 21. |
- Götstedt, Julia, et al.
(author)
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IMRT patient-specific QA using the Delta4 dosimetry system and evaluation based on ICRU 83 recommendations
- 2013
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In: Journal of Physics: Conference Series. - 1742-6588 .- 1742-6596.
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Conference paper (peer-reviewed)abstract
- Patient-specific IMRT QA is dependent on the dosimetry system and the evaluation procedure. The ICRU report 83 provides recommendations of tolerated deviations between measured and calculated absorbed dose distributions for QA of IMRT treatment plans. The result of doing IMRT patient-specific QA with the Delta4 dosimetry system and using the ICRU recommendations for evaluation is studied. To be able to investigate the QA procedure the original IMRT treatment plans were modified in the treatment planning system to create calculated dose distributions with dosimetric deviations from the original treatment plans. The modified dose distributions were compared to the dose distributions from the Delta4 measurements of the original treatment plans and the differences were evaluated with criteria and tolerance levels according to the recommendations from ICRU. The evaluation for all 28 modified dose distributions have gamma passing rates higher than the tolerance level recommended from ICRU and will therefore pass the patient-specific QA. More than half of the evaluations have a gamma passing rate of 100 %. Evaluation of the differences between the modified and the original calculated dose distributions revealed in several cases large unacceptable dose differences in the PTV volumes and the organs at risk, for example an increase in the near-maximum dose D 2% to the spinal cord of 5.5 Gy. This study indicates that patient-specific QA with the Delta4 dosimetry system and the ICRU recommendations for evaluation can not be used to distinguish differences between planned and measured dose of dosimetrical relevance.
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| 22. |
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| 23. |
- Sarudis, Sebastian, 1981, et al.
(author)
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Systematic evaluation of lung tumor motion using four-dimensional computed tomography
- 2017
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 56:4, s. 525-530
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Journal article (peer-reviewed)abstract
- Background: Respiratory-induced lung tumor motion may decrease robustness and outcome of radiation therapy (RT) if not accounted for. This study provides detailed information on the motion distribution of lung tumors for a group of 126 patients treated with stereotactic body RT.Material and methods: Four-dimensional computed tomography scans were reviewed to assess lung tumor motion. The tumor motion was determined by the center of mass shift based on a rigid registration of the breathing phases containing the largest positional differences in the inferior-superior (IS), left-right (LR), and anterior-posterior (AP) directions. The patients were divided into subgroups depending on tumor diameter (<2.0cm, 2.05.0cm, phi>5.0cm) and tumor location within the lung (upper, middle, or lower lobe). The observed motion distributions were evaluated for each group separately to assess the dependence on tumor size and location. For each tumor size, the motion pattern in each direction (IS, LR, and AP) was analyzed for every tumor moving>5mm. Sinusoidal trigonometric functions were fitted to the measured data using the least mean square method to determine which type of function best describes the motion pattern. Tumor volumes between 1.6 and 52.3cm(3) were evaluated. Mann-Whitney statistical tests were used for statistical analyses.Results: The mean amplitude for the tumors in this study was 1.5mm (LR), 2.5mm (AP), and 6.9mm (IS) while the maximum amplitude was 11.0mm (LR), 9.0mm (AP), and 53.0mm (IS). In total, 95% of the tumors moved 20mm in the IS direction, 3mm in the LR direction, and 6mm in the AP direction. The observed motion distributions showed no statistically significant correlation with tumor size or location within the lung except for motion in the IS direction, where the mean and maximum amplitudes significantly increased for tumors located in the middle and lower parts of the lung. The motion pattern of a tumor in any direction was best described using a squared trigonometric function of the type where A is the maximum amplitude of the motion in the current direction, t is the time of measurement, T is the total time of the breathing cycle and B is a constant used to synchronize the starting point of the breathing cycle.Conclusion: Lung tumor movements were generally larger in the IS direction and the motion amplitude in this direction increased for tumors located in the middle and lower parts of the lungs. Motions in LR or AP showed no such relation. Tumor size was not found to have any correlation with the motion amplitude in any direction. The motion pattern of a lung tumor in any direction is best described with a squared sinusoidal function independently of the tumor size or tumor location.
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| 24. |
- Bales, Chris, et al.
(author)
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Chapter 12: Sorption and Themo-Chemical Storage
- 2005
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In: Thermal energy storage for solar and low energy buildings - State of the art. - Lleida, Spain : Lleida University. - 848409877X
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Book chapter (other academic/artistic)
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| 25. |
- Chockalingam, Priya, et al.
(author)
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Not all beta-blockers are equal in the management of Long QT Syndrome types 1 and 2 : higher recurrence of events under metoprolol
- 2012
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 60:20, s. 2092-2099
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Journal article (peer-reviewed)abstract
- Objectives The purpose of this study was to compare the efficacy of beta-blockers in congenital long QT syndrome (LQTS). Background Beta-blockers are the mainstay in managing LQTS. Studies comparing the efficacy of commonly used beta-blockers are lacking, and clinicians generally assume they are equally effective.Methods Electrocardiographic and clinical parameters of 382 LQT1/LQT2 patients initiated on propranolol (n = 134), metoprolol (n = 147), and nadolol (n = 101) were analyzed, excluding patients <1 year of age at beta-blocker initiation. Symptoms before therapy and the first breakthrough cardiac events (BCEs) were documented.Results Patients (56% female, 27% symptomatic, heart rate 76 +/- 16 beats/min, QTc 472 +/- 46 ms) were started on beta-blocker therapy at a median age of 14 years (interquartile range: 8 to 32 years). The QTc shortening with propranolol was significantly greater than with other beta-blockers in the total cohort and in the subset with QTc >480 ms. None of the asymptomatic patients had BCEs. Among symptomatic patients (n = 101), 15 had BCEs (all syncopes). The QTc shortening was significantly less pronounced among patients with BCEs. There was a greater risk of BCEs for symptomatic patients initiated on metoprolol compared to users of the other 2 beta-blockers combined, after adjustment for genotype (odds ratio: 3.95, 95% confidence interval: 1.2 to 13.1, p = 0.025). Kaplan-Meier analysis showed a significantly lower event-free survival for symptomatic patients receiving metoprolol compared to propranolol/nadolol.Conclusions Propranolol has a significantly better QTc shortening effect compared to metoprolol and nadolol, especially in patients with prolonged QTc. Propranolol and nadolol are equally effective, whereas symptomatic patients started on metoprolol are at a significantly higher risk for BCEs. Metoprolol should not be used for symptomatic LQT1 and LQT2 patients.(J Am Coll Cardiol 2012;60:2092-9) (C) 2012 by the American College of Cardiology Foundation
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| 26. |
- Hunold, A., et al.
(author)
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Assembly of a Rieske non-heme iron oxygenase multicomponent system from Phenylobacterium immobile E DSM 1986 enables pyrazon cis-dihydroxylation in E. coli
- 2021
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In: Applied Microbiology and Biotechnology. - : Springer Science and Business Media Deutschland GmbH. - 0175-7598 .- 1432-0614. ; 105:5, s. 2003-2015
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Journal article (peer-reviewed)abstract
- Abstract: Phenylobacterium immobile strain E is a soil bacterium with a striking metabolism relying on xenobiotics, such as the herbicide pyrazon, as sole carbon source instead of more bioavailable molecules. Pyrazon is a heterocyclic aromatic compound of environmental concern and its biodegradation pathway has only been reported in P. immobile. The multicomponent pyrazon oxygenase (PPO), a Rieske non-heme iron oxygenase, incorporates molecular oxygen at the 2,3 position of the pyrazon phenyl moiety as first step of degradation, generating a cis-dihydrodiendiol. The aim of this work was to identify the genes encoding for each one of the PPO components and enable their functional assembly in Escherichia coli. P. immobile strain E genome sequencing revealed genes encoding for RO components, such as ferredoxin-, reductase-, α- and β-subunits of an oxygenase. Though, P. immobile E displays three prominent differences with respect to the ROs currently characterized: (1) an operon-like organization for PPO is absent, (2) all the elements are randomly scattered in its DNA, (3) not only one, but 19 different α-subunits are encoded in its genome. Herein, we report the identification of the PPO components involved in pyrazon cis-dihydroxylation in P. immobile, its appropriate assembly, and its functional reconstitution in E. coli. Our results contributes with the essential missing pieces to complete the overall elucidation of the PPO from P. immobile. Key points: • Phenylobacterium immobile E DSM 1986 harbors the only described pyrazon oxygenase (PPO). • We elucidated the genes encoding for all PPO components. • Heterologous expression of PPO enabled pyrazon dihydroxylation in E. coli JW5510.
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| 27. |
- Jinek, Martin, et al.
(author)
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A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity
- 2012
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 337:6096, s. 816-821
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Journal article (peer-reviewed)abstract
- Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by using CRISPR RNAs (crRNAs) to guide the silencing of invading nucleic acids. We show here that in a subset of these systems, the mature crRNA that is base-paired to trans-activating crRNA (tracrRNA) forms a two-RNA structure that directs the CRISPR-associated protein Cas9 to introduce double-stranded (ds) breaks in target DNA. At sites complementary to the crRNA-guide sequence, the Cas9 HNH nuclease domain cleaves the complementary strand, whereas the Cas9 RuvC-like domain cleaves the noncomplementary strand. The dual-tracrRNA:crRNA, when engineered as a single RNA chimera, also directs sequence-specific Cas9 dsDNA cleavage. Our study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.
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| 28. |
- Jinek, Martin, et al.
(author)
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Structures of Cas9 Endonucleases Reveal RNA-Mediated Conformational Activation
- 2014
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 343:6176, s. 1215-
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Journal article (peer-reviewed)abstract
- Type II CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems use an RNA-guided DNA endonuclease, Cas9, to generate double-strand breaks in invasive DNA during an adaptive bacterial immune response. Cas9 has been harnessed as a powerful tool for genome editing and gene regulation in many eukaryotic organisms. We report 2.6 and 2.2 angstrom resolution crystal structures of two major Cas9 enzyme subtypes, revealing the structural core shared by all Cas9 family members. The architectures of Cas9 enzymes define nucleic acid binding clefts, and single-particle electron microscopy reconstructions show that the two structural lobes harboring these clefts undergo guide RNA-induced reorientation to form a central channel where DNA substrates are bound. The observation that extensive structural rearrangements occur before target DNA duplex binding implicates guide RNA loading as a key step in Cas9 activation.
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| 29. |
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| 30. |
- Mucci, Nadia, et al.
(author)
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Genetic diversity and landscape genetic structure of otter (Lutra lutra) populations in Europe
- 2010
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In: Conservation Genetics. - : Springer Science and Business Media LLC. - 1566-0621 .- 1572-9737. ; 11:2, s. 583-599
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Journal article (peer-reviewed)abstract
- Eurasian otter populations strongly declined and partially disappeared due to global and local causes (habitat destruction, water pollution, human persecution) in parts of their continental range. Conservation strategies, based on reintroduction projects or restoration of dispersal corridors, should rely on sound knowledge of the historical or recent consequences of population genetic structuring. Here we present the results of a survey performed on 616 samples, collected from 19 European countries, genotyped at the mtDNA control-region and 11 autosomal microsatellites. The mtDNA variability was low (nucleotide diversity = 0.0014; average number of pairwise differences = 2.25), suggesting that extant otter mtDNA lineages originated recently. A star-shaped mtDNA network did not allow outlining any phylogeographic inference. Microsatellites were only moderately variable (H (o) = 0.50; H (e) = 0.58, on average across populations), the average allele number was low (observed A (o) = 4.9, range 2.5-6.8; effective A (e) = 2.8; range 1.6-3.7), suggesting small historical effective population size. Extant otters likely originated from the expansion of a single refugial population. Bayesian clustering and landscape genetic analyses however indicate that local populations are genetically differentiated, perhaps as consequence of post-glacial demographic fluctuations and recent isolation. These results delineate a framework that should be used for implementing conservation programs in Europe, particularly if they are based on the reintroduction of wild or captive-reproduced otters.
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| 31. |
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| 32. |
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| 33. |
- Quentmeier, Hilmar, et al.
(author)
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Diffuse Large B Cell Lymphoma Cell Line U2946 : Model for MCL1 Inhibitor Testing
- 2016
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:12
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Journal article (peer-reviewed)abstract
- Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma worldwide. We describe the establishment and molecular characteristics of the DLBCL cell line U-2946. This cell line was derived from a 52-year-old male with DLBCL. U-2946 cells carried the chromosomal translocation t(8; 14) and strongly expressed MYC, but not the mature B-cell lymphoma associated oncogenes BCL2 and BCL6. Instead, U-2946 cells expressed the antiapoptotic BCL2 family member MCL1 which was highly amplified genomically (14n). MCL1 amplification is recurrent in DLBCL, especially in the activated B cell (ABC) variant. Results of microarray expression cluster analysis placed U-2946 together with ABC-, but apart from germinal center (GC)-type DLBCL cell lines. The 1q21.3 region including MCL1 was focally coamplified with a short region of 17p11.2 (also present at 14n). The MCL1 inhibitor A-1210477 triggered apoptosis in U-2946 (MCL1(pos)/BCL2(neg)) cells. In contrast to BCL2(pos) DLBCL cell lines, U-2946 did not respond to the BCL2 inhibitor ABT-263. In conclusion, the novel characteristics of cell line U-2946 renders it a unique model system to test the function of small molecule inhibitors, especially when constructing a panel of DLBCL cell lines expressing broad combinations of antiapoptotic BCL2-family members.
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| 34. |
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| 35. |
- Schaberg, T, et al.
(author)
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[Tuberculosis Guideline for Adults - Guideline for Diagnosis and Treatment of Tuberculosis including LTBI Testing and Treatment of the German Central Committee (DZK) and the German Respiratory Society (DGP)]
- 2017
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In: Pneumologie (Stuttgart, Germany). - : Georg Thieme Verlag KG. - 1438-8790 .- 0934-8387. ; 71:6, s. 325-397
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Journal article (peer-reviewed)abstract
- In Deutschland ist seit 2015 ein deutlicher Anstieg der gemeldeten Tuberkulosefälle zu verzeichnen. Zurückzuführen ist dieser vor allem auf die aktuell vermehrte Migration. Durch die niedrige Inzidenz in den vorhergehenden Jahren konzentriert sich die Erfahrung im Umgang mit Tuberkulose immer mehr auf spezialisierte Zentren. Pneumologen wie auch andere Fachbereiche sind nun aber wieder häufiger an der Behandlung einer Tuberkulose beteiligt, sodass Fachwissen zur Standardtherapie wie auch zu selteneren Therapiesituationen benötigt wird. Die aktuelle Leitlinie zur Diagnostik und Therapie, einschließlich Chemoprävention und -prophylaxe im Erwachsenenalter fasst den derzeitigen Wissensstand zusammen und passt die Empfehlungen an die Situation in Deutschland an. Realisiert wurde die AWMF S2k-Leitlinie durch das Deutsche Zentralkomitee zur Bekämpfung der Tuberkulose e. V. (DZK) im Auftrag der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V. (DGP). Zur Behandlung der Tuberkulose im pädiatrischen Bereich wird in Kürze eine eigenständige Leitlinie der entsprechenden Fachgesellschaften veröffentlicht. Im Vergleich zu den Empfehlungen von 2012 sind eigenständige Kapitel zur Labordiagnostik und zum therapeutischen Medikamentenmanagement entstanden. Die Kapitel Mehrfachresistenzen gegen Medikamente der Standardtherapie, HIV-Koinfektion und die Übersicht der Arzneimittel wurden erweitert. Die umfangreiche Überarbeitung der Empfehlungen soll Ärzten und auch anderen Beschäftigten im Gesundheitswesen helfen, den aktuellen Herausforderungen im Umgang mit dem selten gewordenen Tuberkuloseerreger zu begegnen.
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| 36. |
- Syrén, Per-Olof, et al.
(author)
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Squalene-hopene cyclases : evolution, dynamics and catalytic scope
- 2016
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In: Current opinion in structural biology. - : Elsevier. - 0959-440X .- 1879-033X. ; 41, s. 73-82
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Journal article (peer-reviewed)abstract
- Herein we highlight recent mechanistic findings on the impact of solvent dynamics on catalysis displayed by squalene-hopene cyclases (SHCs). These fascinating biocatalysts that appeared early during the evolution of terpene biosynthetic machineries exploit a catalytic aspartic acid donating the anti-oriented proton to the terminal C. C double bond of pre-folded isoprenoid substrates. We review how the unusual strength of this Brønsted acid can be used to harness a plethora of non-natural protonation-driven reactions in a plastic enzyme fold. Moreover, recent results underline how the reaction termination by deprotonation or water addition is governed by the spatial location of water in the active site. Site-directed mutagenesis of amino acids located in the hydrophobic binding pocket allows for the generation of novel catalytic function by active site reshaping with relatively small enzyme libraries. A deepened understanding of triterpene cyclase dynamics in concert with chemical expertise thus have a great potential to allow for the biocatalytic manufacturing of tailored building bricks that would expand the chemical repertoire currently found in nature.
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| 37. |
- Waldenberg, Christian, 1987, et al.
(author)
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Dose integration and dose rate characteristics of a NiPAM polymer gel MRI dosimeter system
- 2017
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 847:1
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Journal article (peer-reviewed)abstract
- The normoxic polymer gel dosimeter based on N-isopropyl acrylamide (NiPAM) is a promising full 3D-dosimeter with high spatial resolution and near tissue equivalency. NiPAM gel samples were irradiated to different doses using a linear accelerator. The absorbed dose was evaluated using MRI and statistical significance of the analysed data was calculated. The analysis was carried out using an in-house developed software. It was found that the gel dosimeter responded linearly to the absorbed dose. The gel exhibited a dose rate dependence, as well as a dependence on the sequential beam irradiation scheme. A higher dose rate, as well as a higher dose per sequential beam, resulted in a lower dose response.
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