| 1. |
- Achterberg, A., et al.
(författare)
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Detection of atmospheric muon neutrinos with the IceCube 9-string detector
- 2007
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Ingår i: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 1550-7998. ; 76:2, s. 027101-
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Tidskriftsartikel (refereegranskat)abstract
- The IceCube neutrino detector is a cubic kilometer TeV to PeV neutrino detector under construction at the geographic South Pole. The dominant population of neutrinos detected in IceCube is due to meson decay in cosmic-ray air showers. These atmospheric neutrinos are relatively well understood and serve as a calibration and verification tool for the new detector. In 2006, the detector was approximately 10% completed, and we report on data acquired from the detector in this configuration. We observe an atmospheric neutrino signal consistent with expectations, demonstrating that the IceCube detector is capable of identifying neutrino events. In the first 137.4 days of live time, 234 neutrino candidates were selected with an expectation of 211 +/- 76.1(syst)+/- 14.5(stat) events from atmospheric neutrinos.
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| 4. |
- Kandolf-Sekulovic, L, et al.
(författare)
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Which medical disciplines diagnose and treat melanoma in Europe in 2019? A survey of experts from melanoma centres in 27 European countries.
- 2021
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Ingår i: Journal of the European Academy of Dermatology and Venereology : JEADV. - : Wiley. - 1468-3083 .- 0926-9959. ; 35:5, s. 1129-1132
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of melanoma is increasing. This places significant burden on societies to provide efficient cancer care. The European Cancer Organisation recently published the essential requirements for quality melanoma care. The present study is aimed for the first time to roughly estimate the extent to which these requirements have been met in Europe.A web-based survey of experts from melanoma centres in 27 European countries was conducted from 1 February to 1 August 2019. Data on diagnostic techniques, surgical and medical treatment, organization of cancer care and education were collected and correlated with national health and economic indicators and mortality-to-incidence ratio (MIR) as a surrogate for survival. Univariate linear regression analysis was performed to evaluate the correlations. SPSS software was used. Statistical significance was set at P<0.05.The MIR was lower in countries with a high health expenditure per capita and with a higher numbers of general practitioners (GPs) and surgeons (SURG) per million inhabitants. In these countries, GPs and dermatologists (DER) were involved in melanoma detection; high percentage of DER used dermatoscopy and were involved in the follow-up of all melanoma stages; both medical oncologists (ONC) and dermato-oncologists administered systemic treatments; and patients had better access to sentinel lymph node biopsy and were treated within multidisciplinary tumour boards.Based on these first estimates, the greater involvement of GPs in melanoma detection; the greater involvement of highly trained DER in dermatoscopy, dermatosurgery, follow-up and the systemic treatment of melanoma; and the provision of ongoing dermato-oncology training for pathologists, SURG, DER and ONC are necessary to provide an optimal melanoma care pathway. A comprehensive analysis of the melanoma care pathway based on clinical melanoma registries will be needed to more accurately evaluate these first insights.
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| 5. |
- Keilholz, U., et al.
(författare)
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ESMO consensus conference recommendations on the management of metastatic melanoma: under the auspices of the ESMO Guidelines Committee
- 2020
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 31:11, s. 1435-1448
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Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) held a consensus conference on melanoma on 5-7 September 2019 in Amsterdam, The Netherlands. The conference included a multidisciplinary panel of 32 leading experts in the management of melanoma. The aim of the conference was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where available evidence is either limited or conflicting. The main topics identified for discussion were (i) the management of locoregional disease; (ii) targeted versus immunotherapies in the adjuvant setting; (iii) targeted versus immunotherapies for the first-line treatment of metastatic melanoma; (iv) when to stop immunotherapy or targeted therapy in the metastatic setting; and (v) systemic versus local treatment for brain metastases. The expert panel was divided into five working groups to each address questions relating to one of the five topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the results relating to the management of metastatic melanoma, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.
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| 6. |
- Michielin, O., et al.
(författare)
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ESMO consensus conference recommendations on the management of locoregional melanoma: under the auspices of the ESMO Guidelines Committee
- 2020
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 31:11, s. 1449-1461
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Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) held a consensus conference on melanoma on 5-7 September 2019 in Amsterdam, The Netherlands. The conference included a multidisciplinary panel of 32 leading experts in the management of melanoma. The aim of the conference was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where available evidence is either limited or conflicting. The main topics identified for discussion were: (i) the management of locoregional disease; (ii) targeted versus immunotherapies in the adjuvant setting; (iii) targeted versus immunotherapies for the first-line treatment of metastatic melanoma; (iv) when to stop immunotherapy or targeted therapy in the metastatic setting; and (v) systemic versus local treatment of brain metastases. The expert panel was divided into five working groups in order to each address questions relating to one of the five topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the results relating to the management of locoregional melanoma, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.
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| 9. |
- Lindström, Björn, et al.
(författare)
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Results of UFO dynamics studies with beam in the LHC
- 2018
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Ingår i: Journal of Physics, Conference Series. - : Institute of Physics Publishing (IOPP). - 1742-6588 .- 1742-6596. ; 1067:2
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Tidskriftsartikel (refereegranskat)abstract
- Micrometer sized particles entering the LHC beam (the so called Unidentified Falling Objects or UFOs) are a known cause of localized beam losses since the beginning of high intensity beam operation, however the origin of these particles is not fully known. Their effect limits LHC availability by causing premature dumps due to excessive beam losses and occasionally even magnet quenches. This could become an important limitation for future accelerators such as the High Luminosity upgrade of the LHC (HL-LHC) and the Future Circular Collider (FCC). The dynamics of these UFOs was investigated in two dedicated experiments. In the first experiment, it was shown that the transverse movements of these particles can be studied by observing bunch-by-bunch losses from bunches with different horizontal and vertical emittances. In the second experiment, UFO-like events around the 16L2 interconnect in the LHC, which has seen intense UFO activity in 2017, were studied with the above method. This paper summarizes the results of both experiments.
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| 16. |
- Biermann, Frank, et al.
(författare)
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Scientific evidence on the political impact of the Sustainable Development Goals
- 2022
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Ingår i: Nature Sustainability. - : Springer Nature. - 2398-9629. ; 5:9, s. 795-800
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Tidskriftsartikel (refereegranskat)abstract
- In 2015, the United Nations agreed on 17 Sustainable Development Goals as the central normative framework for sustainable development worldwide. The effectiveness of governing by such broad global goals, however, remains uncertain, and we lack comprehensive meta-studies that assess the political impact of the goals across countries and globally. We present here condensed evidence from an analysis of over 3,000 scientific studies on the Sustainable Development Goals published between 2016 and April 2021. Our findings suggests that the goals have had some political impact on institutions and policies, from local to global governance. This impact has been largely discursive, affecting the way actors understand and communicate about sustainable development. More profound normative and institutional impact, from legislative action to changing resource allocation, remains rare. We conclude that the scientific evidence suggests only limited transformative political impact of the Sustainable Development Goals thus far.
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| 24. |
- Veldwijk, Jorien, et al.
(författare)
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Exploring how individuals complete the choice tasks in a discrete choice experiment : an interview study
- 2016
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Ingår i: BMC Medical Research Methodology. - : Springer Science and Business Media LLC. - 1471-2288. ; 16:45
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTo be able to make valid inferences on stated preference data from a Discrete Choice Experiment (DCE) it is essential that researchers know if participants were actively involved, understood and interpreted the provided information correctly and whether they used complex decision strategies to make their choices and thereby acted in accordance with the continuity axiom.MethodsDuring structured interviews, we explored how 70 participants evaluated and completed four discrete choice tasks aloud. Hereafter, additional questions were asked to further explore if participants understood the information that was provided to them and whether they used complex decision strategies (continuity axiom) when making their choices. Two existing DCE questionnaires on rotavirus vaccination and prostate cancer-screening served as case studies.ResultsA large proportion of the participants was not able to repeat the exact definition of the risk attributes as explained to them in the introduction of the questionnaire. The majority of the participants preferred more optimal over less optimal risk attribute levels. Most participants (66 %) mentioned three or more attributes when motivating their decisions, thereby acting in accordance with the continuity axiom. However, 16 out of 70 participants continuously mentioned less than three attributes when motivating their decision. Lower educated and less literate participants tended to mention less than three attributes when motivating their decision and used trading off between attributes less often as a decision-making strategy.ConclusionThe majority of the participants seemed to have understood the provided information about the choice tasks, the attributes, and the levels. They used complex decision strategies (continuity axiom) and are therefore capable to adequately complete a DCE. However, based on the participants’ age, educational level and health literacy additional, actions should be undertaken to ensure that participants understand the choice tasks and complete the DCE as presumed.
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| 29. |
- Jimenez-Moreno, A. Cecilia, et al.
(författare)
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Patient Preferences in Rare Diseases: A Qualitative Study in Neuromuscular Disorders to Inform a Quantitative Preference Study
- 2021
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Ingår i: Patient. - : Springer Science and Business Media LLC. - 1178-1653 .- 1178-1661.
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionIt has become increasingly important to include patient preference information in decision-making processes for drug development. As neuromuscular disorders represent multisystem, debilitating, and progressive rare diseases with few treatment options, this study aimed to explore unmet health care needs and patient treatment preferences for two neuromuscular disorders, myotonic dystrophy type 1 (DM1) and mitochondrial myopathies (MM) to inform early stages of drug development.MethodsFifteen semi-structured interviews and five focus group discussions (FGDs) were held with DM1 and MM adult patients and caregivers. Topics discussed included (1) reasons for study participation; (2) disease signs/symptoms and their impact on daily lives; (3) top desired benefits; and (4) acceptability of risks and tolerance levels for a hypothetical new treatment. Data were analyzed following a thematic ‘code’ approach.ResultsA total of 52 participants representing a wide range of disease severities participated. ‘Muscle strength’ and ‘energy and endurance’ were the disease-related unmet needs most often mentioned. Additionally, improved ‘balance’, ‘cognition’ and ‘gut function’ were the top desired treatment benefits, while ‘damage to the liver, kidneys or eyes’ was the most concerning risk. Factors influencing their tolerance to risks related to previously having experienced the risk and differentiation between permanent and temporary risks. A few differences were elicited between patients and caregivers.ConclusionsThis qualitative study provided an open forum to elicit treatment-desired benefits and acceptable risks to be established by patients themselves. These findings can inform decisions for developing new treatments and the design of clinical trials for DM1 and MM.
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| 31. |
- Lechner, A., et al.
(författare)
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Dust-induced beam losses in the cryogenic arcs of the CERN Large Hadron Collider
- 2022
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Ingår i: Physical Review Accelerators and Beams. - : American Physical Society. - 2469-9888. ; 25:4
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Tidskriftsartikel (refereegranskat)abstract
- The interaction of dust particles with the LHC proton beams accounts for a major fraction of irregular beam loss events observed in LHC physics operation. The events cease after a few beam revolutions because of the expulsion of dust particles from the beam once they become ionized in the transverse beam tails. Despite the transient nature of these events, the resulting beam losses can trigger beam aborts or provoke quenches of superconducting magnets. In this paper, we study the characteristics of beam-dust particle interactions in the cryogenic arcs by reconstructing key observables like nuclear collision rates, loss durations and integral losses per event. The study is based on events recorded during 6.5 TeVoperation with stored beam intensities of up to similar to 3 x 10(14) protons per beam. We show that inelastic collision rates can reach almost 10(12) collisions per second, resulting in a loss of up to similar to 1.6 x 10(8) protons per event. We demonstrate that the experimental distributions and their dependence on beam parameters can be described quantitatively by a previously developed simulation model if dust particles are assumed to be attracted by the beam. The latter finding is consistent with recent time profile studies and yields further evidence that dust particles carry a negative charge when entering the beam. We also develop different hypotheses regarding the absence of higher-loss events in the measurements, although such events are theoretically not excluded by the simulation model. The results provide grounds for predicting dust-induced beam losses in the presence of higher-intensity beams in future runs of the High-Luminosity LHC.
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| 33. |
- Naldi, L., et al.
(författare)
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Comparators, study duration, outcome measures and sponsorship in therapeutic trials of psoriasis: update of the EDEN Psoriasis Survey 2001-2006
- 2010
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 162:2, s. 384-389
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Tidskriftsartikel (refereegranskat)abstract
- Background Several new therapeutic options for psoriasis have been tested in clinical trials in recent years. Choice of comparator, study duration and outcome measures are critical for interpreting application of trial results to clinical practice. Objectives We examined whether these trial aspects have changed substantially in recent years in comparison with the past. Methods A systematic search and evaluation of all randomized controlled trials (RCTs) for psoriasis published from January 2001 up to December 2006 in 14 leading medical and dermatological journals, compared with those published from 1977 to 2000. Results There were 140 RCTs of psoriasis in the period 2001-2006 and 249 in the period 1977-2000. The proportion of placebo-controlled studies increased from 44.6% to 69.3%. The median study duration increased from 7 weeks to 12 weeks. The proportion of studies adopting the Psoriasis Area and Severity Index score as an outcome increased from 30.6% to 57.7%, while the number of studies incorporating a quality of life measure increased from only one (0.4%) to 12 studies (7.7%). The proportion of studies sponsored by pharmaceutical companies increased from 61.0% to 73.7%. Conclusions Despite the increased number of new options, the number of head-to-head comparative trials has decreased and most trials focus on short-term effects, probably reflecting the increased influence of industrial sponsorship on the research agenda.
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| 35. |
- Strömstedt, Adam A., et al.
(författare)
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Selective membrane disruption by the cyclotide kalata B7: complex ions and essential functional groups in the phosphatidylethanolamine binding pocket
- 2016
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 1878-2434 .- 0005-2736. ; 1858:6, s. 1317-1327
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Tidskriftsartikel (refereegranskat)abstract
- The cyclic cystine knot plant peptides called cyclotides are active against a wide variety of organisms. This is primarily achieved through membrane binding and disruption, in part deriving from a high affinity for phosphatidylethanolamine (PE) lipids. Some cyclotides, such as kalata B7 (kB7), form complexes with divalent cations in a pocket associated with the tyrosine residue at position 15 (Tyr15). In the current work we explore the effect of cations on membrane leakage caused by cyclotides kB1, kB2 and kB7, and we identify a functional group that is essential for PE selectivity. The presence of PE-lipids in liposomes increased the membrane permeabilizing potency of the cyclotides, with the potency of kB7 increasing by as much as 740-fold. The divalent cations Mn(2+), Mg(2+) and Ca(2+) had no apparent effect on PE selectivity. However, amino acid substitutions in kB7 proved that Tyr15 is crucial for PE-selective membrane permeabilization on various liposome systems. Although the tertiary structure of kB7 was maintained, as reflected by the NMR solution structure, mutating Tyr into Ser at position 15 resulted in substantially reduced PE selectivity. Ala substitution at the same position produced a similar reduction in PE selectivity, while substitution with Phe maintained high selectivity. We conclude that the phenyl ring in Tyr15 is critical for the high PE selectivity of kB7. Our results suggest that PE-binding and divalent cation coordination occur in the same pocket without adverse effects of competitive binding for the phospholipid.
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