| 1. |
- Dam-Larsen, Sanne, et al.
(author)
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Best practice in placement of percutaneous endoscopic gastrostomy with jejunal extension tube for continuous infusion of levodopa carbidopa intestinal gel in the treatment of selected patients with Parkinsons disease in the Nordic region
- 2015
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In: Scandinavian Journal of Gastroenterology. - : TAYLOR and FRANCIS LTD. - 0036-5521 .- 1502-7708. ; 50:12, s. 1500-1507
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Journal article (peer-reviewed)abstract
- Objective. Continuous infusion of levodopa carbidopa intestinal gel (LCIG) is associated with a significant improvement in the symptoms and quality of life of selected patients with advanced Parkinsons disease. Percutaneous endoscopic gastrostomy with jejunal extension (PEG/J) was first described in 1998 and has become the most common and standard technique for fixing the tubing in place for LCIG infusion. Material and methods. A workshop was held in Stockholm, Sweden, to discuss the PEG/J placement for the delivery of LCIG in Parkinsons disease patients with the primary goal of providing guidance on best practice for the Nordic countries. Results. Suggested procedures for preparation of patients for PEG/J placement, aftercare, troubleshooting and redo-procedures for use in the Nordic region are described and discussed. Conclusions. LCIG treatment administered through PEG/J-tubes gives a significant increase in quality of life for selected patients with advanced Parkinsons disease. Although minor complications are common, serious complications are infrequent, and the tube insertion procedures have a good safety record. Further development of delivery systems and evaluation of approaches designed to reduce the demand for redo endoscopy are required.
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| 2. |
- Ladds, Marcus J. G. W., et al.
(author)
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A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Journal article (peer-reviewed)abstract
- The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.
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| 3. |
- Lagerlöf, Ingemar, et al.
(author)
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No excess long-term mortality in stage I-IIA Hodgkin lymphoma patients treated with ABVD and limited field radiotherapy
- 2020
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In: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 188:5, s. 685-691
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Journal article (peer-reviewed)abstract
- When treating limited stage classical Hodgkin lymphoma (cHL), balancing treatment efficacy and toxicity is important. Toxicities after extended-field radiotherapy are well documented. Investigators have aimed at reducing toxicity without compromising efficacy, mainly by using combined modality treatment (CMT), i.e. chemotherapy and limited-field radiotherapy. In some clinical trials, radiotherapy has been omitted. We evaluated 364 patients with stage I-IIA cHL treated between 1999 and 2005. Patients were treated with two or four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) according to presence of risk factors, followed by 30 Gy limited-field (reduced compared to involved-field) radiotherapy. After a median follow-up of 16 years for survival, freedom from progression at five and ten years was 93% and overall survival at 5 and 10 years was 98% and 96%, respectively. Only two relapses, out of 27, occurred after more than 5 years. There was no excess mortality compared to the general population. Of the analysed subgroups, only patients with progression within five years showed significant excess mortality. The absence of excess mortality questions the concept of omitting radiotherapy after short-term chemotherapy, a strategy that has been associated with an elevated risk of relapse but not yet with a proven reduced long-term excess mortality.
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| 4. |
- McCrea, Ian, et al.
(author)
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The science case for the EISCAT_3D radar
- 2015
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In: Progress in Earth and Planetary Science. - : Springer Science and Business Media LLC. - 2197-4284. ; 2:1
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Research review (peer-reviewed)abstract
- The EISCAT (European Incoherent SCATer) Scientific Association has provided versatile incoherent scatter (IS) radar facilities on the mainland of northern Scandinavia (the EISCAT UHF and VHF radar systems) and on Svalbard (the electronically scanning radar ESR (EISCAT Svalbard Radar) for studies of the high-latitude ionised upper atmosphere (the ionosphere). The mainland radars were constructed about 30years ago, based on technological solutions of that time. The science drivers of today, however, require a more flexible instrument, which allows measurements to be made from the troposphere to the topside ionosphere and gives the measured parameters in three dimensions, not just along a single radar beam. The possibility for continuous operation is also an essential feature. To facilitatefuture science work with a world-leading IS radar facility, planning of a new radar system started first with an EU-funded Design Study (2005-2009) and has continued with a follow-up EU FP7 EISCAT_3D Preparatory Phase project (2010-2014). The radar facility will be realised by using phased arrays, and a key aspect is the use of advanced software and data processing techniques. This type of software radar will act as a pathfinder for other facilities worldwide. The new radar facility will enable the EISCAT_3D science community to address new, significant science questions as well as to serve society, which is increasingly dependent on space-based technology and issues related to space weather. The location of the radar within the auroral oval and at the edge of the stratospheric polar vortex is also ideal for studies of the long-term variability in the atmosphere and global change. This paper is a summary of the EISCAT_3D science case, which was prepared as part of the EU-funded Preparatory Phase project for the new facility. Three science working groups, drawn from the EISCAT user community, participated in preparing this document. In addition to these working group members, who are listed as authors, thanks are due to many others in the EISCAT scientific community for useful contributions, discussions, and support.
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| 5. |
- Oyama, Shin-ichiro, et al.
(author)
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Auroral molecular-emission effects on the atomic oxygen line at 777.4 nm
- 2018
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In: Earth Planets and Space. - : SPRINGEROPEN. - 1343-8832 .- 1880-5981. ; 70
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Journal article (peer-reviewed)abstract
- One of the representative auroral emission lines that radiates from F-region heights and is measurable on the ground is the 777.4nm line from excited atomic oxygen. This line has been adopted, along with another E-region emission line, for example 427.8nm, to estimate the mean energy and total energy flux of precipitating auroral electrons. The influence of emissions from part of the molecular nitrogen band, which mainly radiate from E-region heights, should be carefully evaluated because it might overlap the 777.4nm atomic oxygen line in the spectrum. We performed statistical analysis of auroral spectrograph measurements that were obtained during the winter of 2016-2017 in TromsO, Norway, to derive the ratio of the intensity of the 777.4nm atomic oxygen line to that of the net measurement through a typically used optical filter with a full width at half maximum of a few nm. The ratio had a negative trend against geomagnetic activity, with a primary distribution of 0.5-0.7 and a minimum value of 0.3 for the most active auroral condition in this study. This result suggests that the 30-50% emission intensities measured through the optical filter may be from the molecular nitrogen band.
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| 6. |
- Rexer, Theresa, et al.
(author)
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Conditions for Topside Ion Line Enhancements
- 2021
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In: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 126:7
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Journal article (peer-reviewed)abstract
- Enhanced ion line spectra as a response to magnetic field-aligned high frequency (HF) pumping of the overdense polar ionosphere with left-handed circular polarization, can be observed at the top and bottomside F-region ionosphere under certain conditions. The European Incoherent Scatter (EISCAT) UHF radar was directed in magnetic zenith on October 18th and 19th, 2017 while stepping the pump frequency of the EISCAT Heating facility both upward and downward across the double resonance frequency of the fourth harmonic of the electron gyrofrequency and the local upper hybrid frequency, in a 2-min-on, 5-min-30-s-off pump cycle. We present observations of two separate cases of topside HF-enhanced ion lines (THFIL). THFIL simultaneous to bottomside HFIL (BHFIL), and conditioned by the relative proximity of the HF pump frequency to the bottomside double resonance frequency, consistent with previous observations (Rexer et al., 2018, ) were observed for HF pulses on 19th October. Recurring THFIL appearing after BHFIL have faded and conditioned by the relative proximity to the double resonance frequency on the topside ionosphere, were observed on 18th October. The THFIL are consistent with transionospheric propagation through artificial radio windows by L mode guiding of the pump wave, facilitated by large scale density ducts present in the plasma.
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| 7. |
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| 8. |
- Tuttle, Sam, et al.
(author)
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Horizontal electric fields from flow of auroral O+(P-2) ions at sub-second temporal resolution
- 2020
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In: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 38:4, s. 845-859
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Journal article (peer-reviewed)abstract
- Electric fields are a ubiquitous feature of the ionosphere and are intimately linked with aurora through particle precipitation and field-aligned currents. They exhibit order-of-magnitude changes on temporal and spatial scales of seconds and kilometres respectively which are not easy to measure; knowing their true magnitude and temporal variability is important for a theoretical understanding of auroral processes. We present a unique method to estimate ionospheric electric fields in the region close to (kilometre scale) a dynamic auroral arc by solving the continuity equation for the metastable O+(P-2) ions, which emit as they move under the influence of electric fields during their 5 s lifetime. The main advantage of this optical method is the increase in temporal resolution over other methods such as ground-based radars. Simultaneous measurements of emission at 732.0 nm (from the O+(P-2) ions) and prompt emissions at 673.0 nm (N-2) and 777.4 nm (O), all at high spatial (100 m) and temporal (0.05 s) resolution, are used in the solution of the continuity equation, which gives the dynamic changes of the O+ ion population at all heights in a 3D volume close to the magnetic zenith. Perspective effects are taken into account by a new geometric method, which is based on an accurate estimate of the magnetic zenith position. The emissions resulting from the metastable ions are converted to brightness images by projecting them onto the plane of the ground, and the projected images are then compared with the measured images. The flow velocity of the ions is a free parameter in the solution of the continuity equation; the value that minimises the difference between the modelled and observed images is the extracted flow velocity at each time step. We demonstrate the method with an example event during the passage of a brightening arc feature, lasting about 10 s, in which the inferred electric fields vary between 20 and 120 mV m(-1). These inferred electric fields are compared with SuperDARN measurements, which have an average value of 30 mV m(-1). An excellent agreement is found in the magnitude and direction of the background electric field; an increase in magnitude during the brightening of the arc feature supports theories of small-scale auroral arc formation and electrodynamics.
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