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| 2. |
- Acharya, B. S., et al.
(författare)
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Introducing the CTA concept
- 2013
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
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| 3. |
- Picetti, Edoardo, et al.
(författare)
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Early management of adult traumatic spinal cord injury in patients with polytrauma : a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS)
- 2024
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Ingår i: World Journal of Emergency Surgery. - : BioMed Central (BMC). - 1749-7922. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies.Methods: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted.Results: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak).Conclusions: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients.
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| 5. |
- Weaver, T. E., et al.
(författare)
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Long-term effects of solriamfetol on quality of life and work productivity in participants with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea
- 2021
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Ingår i: JOURNAL OF CLINICAL SLEEP MEDICINE. - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 17:10, s. 1995-2007
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: Solriamfetol, a dopamine/norepinephdne reuptake inhibitor, is approved in the United States and European Union for excessive daytime sleepiness in adults with narcolepsy (75-150 mg/day) or obstructive sleep apnea (OSA; 37.5-150 mg/day). In 12-week studies, solriamfetol was associated with improvements in quality of life in participants with narcolepsy or OSA. These analyses evaluated the long-term effects of solriamfetol on quality of life. Methods: Participants with narcolepsy or OSA who completed previous solriamfetol studies were eligible. A2-week titration was followed by a maintenance phase <= 50 weeks (stable doses:75, 150, or 300 mg/day). Quality of life assessments included Functional Outcomes of Sleep Questionnaire short version, Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, and 36-Item Short Form Health Survey version 2. Mean (standard deviation) changes from baseline to end of study were evaluated. Data were summarized descriptively. Adverse events were assessed. Results: Safety population comprised 643 participants (417 OSA, 226 narcolepsy). Solriamfetol improved Functional Outcomes of Sleep Questionnaire short version Total scores (mean change [standard deviation], 3.7 [3.0] and 36-Item Short Form Health Survey version 2 Physical and Mental Component Summary scores (3.1[6.9] and 4.3 [8.4 respectively); improvements were sustained throughout treatment. On Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, solriamfetol reduced (improved) % presenteeism, % overall work impairment, and % activity impairment by a minimum of 25%. Common adverse events (>= 5%): headache, nausea, nasopharyngitis, insomnia, dry mouth, anxiety, decreased appetite, and upper respiratory tract infection. Conclusions: Long-term solriamfetol treatment was associated with clinically meaningful, sustained improvements in functional status, work productivity, and quality of life for up to 52 weeks. Adverse events were similar between narcolepsy and OSA.
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| 6. |
- Kaltenbaek, Rainer, et al.
(författare)
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Macroscopic Quantum Resonators (MAQRO) : 2015 update
- 2016
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Ingår i: EPJ Quantum Technology. - : Springer Berlin/Heidelberg. - 2196-0763. ; 3:1
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Forskningsöversikt (refereegranskat)abstract
- Do the laws of quantum physics still hold for macroscopic objects - this is at the heart of Schrodinger's cat paradox - or do gravitation or yet unknown effects set a limit for massive particles? What is the fundamental relation between quantum physics and gravity? Ground-based experiments addressing these questions may soon face limitations due to limited free-fall times and the quality of vacuum and microgravity. The proposed mission Macroscopic Quantum Resonators (MAQRO) may overcome these limitations and allow addressing such fundamental questions. MAQRO harnesses recent developments in quantum optomechanics, high-mass matter-wave interferometry as well as state-of-the-art space technology to push macroscopic quantum experiments towards their ultimate performance limits and to open new horizons for applying quantum technology in space. The main scientific goal is to probe the vastly unexplored 'quantum-classical' transition for increasingly massive objects, testing the predictions of quantum theory for objects in a size and mass regime unachievable in ground-based experiments. The hardware will largely be based on available space technology. Here, we present the MAQRO proposal submitted in response to the 4th Cosmic Vision call for a medium-sized mission (M4) in 2014 of the European Space Agency (ESA) with a possible launch in 2025, and we review the progress with respect to the original MAQRO proposal for the 3rd Cosmic Vision call for a medium-sized mission (M3) in 2010. In particular, the updated proposal overcomes several critical issues of the original proposal by relying on established experimental techniques from high-mass matter-wave interferometry and by introducing novel ideas for particle loading and manipulation. Moreover, the mission design was improved to better fulfill the stringent environmental requirements for macroscopic quantum experiments.
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| 7. |
- Swen, JesseJ, et al.
(författare)
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A 12-gene pharmacogenetic panel to prevent adverse drug reactions : an open-label, multicentre, controlled, cluster-randomised crossover implementation study
- 2023
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 401:10374, s. 347-356
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Tidskriftsartikel (refereegranskat)abstract
- Background: The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene-drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed.Methods: We conducted an open-label, multicentre, controlled, cluster-randomised, crossover implementation study of a 12-gene pharmacogenetic panel in 18 hospitals, nine community health centres, and 28 community pharmacies in seven European countries (Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK). Patients aged 18 years or older receiving a first prescription for a drug clinically recommended in the guidelines of the Dutch Pharmacogenetics Working Group (ie, the index drug) as part of routine care were eligible for inclusion. Exclusion criteria included previous genetic testing for a gene relevant to the index drug, a planned duration of treatment of less than 7 consecutive days, and severe renal or liver insufficiency. All patients gave written informed consent before taking part in the study. Participants were genotyped for 50 germline variants in 12 genes, and those with an actionable variant (ie, a drug-gene interaction test result for which the Dutch Pharmacogenetics Working Group [DPWG] recommended a change to standard-of-care drug treatment) were treated according to DPWG recommendations. Patients in the control group received standard treatment. To prepare clinicians for pre-emptive pharmacogenetic testing, local teams were educated during a site-initiation visit and online educational material was made available. The primary outcome was the occurrence of clinically relevant adverse drug reactions within the 12-week follow-up period. Analyses were irrespective of patient adherence to the DPWG guidelines. The primary analysis was done using a gatekeeping analysis, in which outcomes in people with an actionable drug-gene interaction in the study group versus the control group were compared, and only if the difference was statistically significant was an analysis done that included all of the patients in the study. Outcomes were compared between the study and control groups, both for patients with an actionable drug-gene interaction test result (ie, a result for which the DPWG recommended a change to standard-of-care drug treatment) and for all patients who received at least one dose of index drug. The safety analysis included all participants who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03093818 and is closed to new participants.Findings: Between March 7, 2017, and June 30, 2020, 41 696 patients were assessed for eligibility and 6944 (51.4 % female, 48.6% male; 97.7% self-reported European, Mediterranean, or Middle Eastern ethnicity) were enrolled and assigned to receive genotype-guided drug treatment (n=3342) or standard care (n=3602). 99 patients (52 [1.6%] of the study group and 47 [1.3%] of the control group) withdrew consent after group assignment. 652 participants (367 [11.0%] in the study group and 285 [7.9%] in the control group) were lost to follow-up. In patients with an actionable test result for the index drug (n=1558), a clinically relevant adverse drug reaction occurred in 152 (21 center dot 0%) of 725 patients in the study group and 231 (27.7%) of 833 patients in the control group (odds ratio [OR] 0 center dot 70 [95% CI 0 center dot 54-0 center dot 91]; p=0.0075), whereas for all patients, the incidence was 628 (21.5%) of 2923 patients in the study group and 934 (28. 6%) of 3270 patients in the control group (OR 0.70 [95% CI 0.61-0.79]; p <0.0001).Interpretation: Genotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions and was feasible across diverse European health-care system organisations and settings. Large-scale implementation could help to make drug therapy increasingly safe.
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| 8. |
- van der Wouden, Cathelijne H., et al.
(författare)
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Generating evidence for precision medicine : considerations made by the Ubiquitous Pharmacogenomics Consortium when designing and operationalizing the PREPARE study
- 2020
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Ingår i: Pharmacogenetics & Genomics. - 1744-6872 .- 1744-6880. ; 30:6, s. 131-144
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Pharmacogenetic panel-based testing represents a new model for precision medicine. A sufficiently powered prospective study assessing the (cost-)effectiveness of a panel-based pharmacogenomics approach to guide pharmacotherapy is lacking. Therefore, the Ubiquitous Pharmacogenomics Consortium initiated the PREemptive Pharmacogenomic testing for prevention of Adverse drug Reactions (PREPARE) study. Here, we provide an overview of considerations made to mitigate multiple methodological challenges that emerged during the design.Methods An evaluation of considerations made when designing the PREPARE study across six domains: study aims and design, primary endpoint definition and collection of adverse drug events, inclusion and exclusion criteria, target population, pharmacogenomics intervention strategy, and statistical analyses.Results Challenges and respective solutions included: (1) defining and operationalizing a composite primary endpoint enabling measurement of the anticipated effect, by including only severe, causal, and drug genotype-associated adverse drug reactions; (2) avoiding overrepresentation of frequently prescribed drugs within the patient sample while maintaining external validity, by capping drugs of enrolment; (3) designing the pharmacogenomics intervention strategy to be applicable across ethnicities and healthcare settings; and (4) designing a statistical analysis plan to avoid dilution of effect by initially excluding patients without a gene–drug interaction in a gatekeeping analysis.Conclusion Our design considerations will enable quantification of the collective clinical utility of a panel of pharmacogenomics-markers within one trial as a proof-of-concept for pharmacogenomics-guided pharmacotherapy across multiple actionable gene–drug interactions. These considerations may prove useful to other investigators aiming to generate evidence for precision medicine.
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| 9. |
- Korytowska, M., et al.
(författare)
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Patient-reported pain after surgical removal of leukoplakia - an observational 1-year follow-up study
- 2021
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Ingår i: Acta Odontologica Scandinavica. - : Informa UK Limited. - 0001-6357 .- 1502-3850. ; 79:5, s. 383-9
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Oral leukoplakia (OL) presents as a white lesion of the oral mucosa and is not typically associated with the sensation of pain. OL should be surgically removed when possible because it is considered a potentially malignant oral disorder (PMOD). This study assessed the pain sensations experienced by patients in association with the occurrence and surgical treatment of OL. Methods: Inclusion criteria were: a clinical diagnosis of OL; biopsy excision; and observation for at least 12 months in the ORA-LEU-CAN study. At the first visit, all the patients were asked about the occurrence of symptoms within the lesion. Ninety-four subjects were assessed over a period of 1 year. All patients underwent complete removal of OL. The patient cohort was divided into three sub-groups: (i) no pain before excision and at the 1-year follow-up; (ii) pain before excision; and (iii) pain at the 1-year follow-up. Results: Overall, pain was reported by 21.3% of the patients at the study start whereas 13.8% of the patients reported pain 1 year after surgical treatment. Patient-reported pain from the lesion at study inclusion was significantly associated with lesions found on the lateral side of the tongue (p=.002). Pain reported by patients one year after surgery was significantly related to female gender (p=.038) and the presence of epithelial cell dysplasia (p=.022). Conclusion: We conclude that surgical removal of OL results in a low risk of long-term post-surgical pain. However, OL located on the lateral side of the tongue and in OL with dysplasia are more likely to be associated with pain.
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| 10. |
- Marriott, Heather, et al.
(författare)
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Mutations in the tail and rod domains of the neurofilament heavy-chain gene increase the risk of ALS
- 2024
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Ingår i: Annals of Clinical and Translational Neurology. - : John Wiley & Sons. - 2328-9503.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Neurofilament heavy-chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk.Methods: Genetic data of 11,130 people with ALS and 7,416 controls from the literature and Project MinE were analysed. We performed meta-analyses of published case–control studies reporting NEFH variants, and variant analysis of NEFH in Project MinE whole-genome sequencing data.Results: Fixed-effects meta-analysis found that rare (MAF <1%) missense variants in the tail domain of NEFH increase ALS risk (OR 4.55, 95% CI 2.13–9.71, p < 0.0001). In Project MinE, ultrarare NEFH variants increased ALS risk (OR 1.37 95% CI 1.14–1.63, p = 0.0007), with rod domain variants (mostly intronic) appearing to drive the association (OR 1.45 95% CI 1.18–1.77, pMadsen–Browning = 0.0007, pSKAT-O = 0.003). While in the tail domain, ultrarare (MAF <0.1%) pathogenic missense variants were also associated with higher risk of ALS (OR 1.94, 95% CI 0.86–4.37, pMadsen–Browning = 0.039), supporting the meta-analysis results. Finally, several tail in-frame deletions were also found to affect disease risk, however, both protective and pathogenic deletions were found in this domain, highlighting an intricated architecture that requires further investigation.Interpretation: We showed that NEFH tail missense and in-frame deletion variants, and intronic rod variants are risk factors for ALS. However, they are not variants of large effect, and their functional impact needs to be clarified in further studies. Therefore, their inclusion in routine genetic screening panels should be reconsidered.
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