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  • Aad, G., et al. (författare)
  • 2012
  • swepub:Mat__t (refereegranskat)
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  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Bouyoucef, S E, et al. (författare)
  • Poster Session 2 : Monday 4 May 2015, 08
  • 2015
  • Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
  • Tidskriftsartikel (refereegranskat)
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  • Thoma, B, et al. (författare)
  • An international, interprofessional investigation of the self-reported podcast listening habits of emergency clinicians: A METRIQ Study
  • 2020
  • Ingår i: CJEM. - : Springer Science and Business Media LLC. - 1481-8043 .- 1481-8035. ; 22:1, s. 112-117
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesPodcasts are increasingly being used for medical education. A deeper understanding of usage patterns would inform both producers and researchers of medical podcasts. We aimed to determine how and why podcasts are used by emergency medicine and critical care clinicians.MethodsAn international interprofessional sample (medical students, residents, physicians, nurses, physician assistants, and paramedics) was recruited through direct contact and a multimodal social media (Twitter and Facebook) campaign. Each participant completed a survey outlining how and why they utilize medical podcasts. Recruitment materials included an infographic and study website.Results390 participants from 33 countries and 4 professions (medicine, nursing, paramedicine, physician assistant) completed the survey. Participants most frequently listened to medical podcasts to review new literature (75.8%), learn core material (75.1%), and refresh memory (71.8%). The majority (62.6%) were aware of the ability to listen at increased speeds, but most (76.9%) listened at 1.0 x (normal) speed. All but 25 (6.4%) participants concurrently performed other tasks while listening. Driving (72.3%), exercising (39.7%), and completing chores (39.2%) were the most common. A minority of participants used active learning techniques such as pausing, rewinding, and replaying segments of the podcast. Very few listened to podcasts multiple times.ConclusionsAn international cohort of emergency clinicians use medical podcasts predominantly for learning. Their listening habits (rarely employing active learning strategies and frequently performing concurrent tasks) may not support this goal. Further exploration of the impact of these activities on learning from podcasts is warranted.
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  • Waszak, S. M., et al. (författare)
  • Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort
  • 2018
  • Ingår i: Lancet Oncology. - : Elsevier BV. - 1470-2045. ; 19:6, s. 785-798
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 4069) and 5-year overall survival was 65% (95% CI 5281); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. Interpretation Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. Copyright (c) 2018 The Author(s). Published by Elsevier Ltd.
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  • Sen, P, et al. (författare)
  • Vaccine hesitancy decreases in rheumatic diseases, long-term concerns remain in myositis: a comparative analysis of the COVAD surveys
  • 2023
  • Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 62:10, s. 3291-3301
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveCOVID-19 vaccines have a favorable safety profile in patients with autoimmune rheumatic diseases (AIRDs) such as idiopathic inflammatory myopathies (IIMs); however, hesitancy continues to persist among these patients. Therefore, we studied the prevalence, predictors and reasons for hesitancy in patients with IIMs, other AIRDs, non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs), using data from the two international COVID-19 Vaccination in Autoimmune Diseases (COVAD) e-surveys.MethodsThe first and second COVAD patient self-reported e-surveys were circulated from March to December 2021, and February to June 2022 (ongoing). We collected data on demographics, comorbidities, COVID-19 infection and vaccination history, reasons for hesitancy, and patient reported outcomes. Predictors of hesitancy were analysed using regression models in different groups.ResultsWe analysed data from 18 882 (COVAD-1) and 7666 (COVAD-2) respondents. Reassuringly, hesitancy decreased from 2021 (16.5%) to 2022 (5.1%) (OR: 0.26; 95% CI: 0.24, 0.30, P < 0.001). However, concerns/fear over long-term safety had increased (OR: 3.6; 95% CI: 2.9, 4.6, P < 0.01). We noted with concern greater skepticism over vaccine science among patients with IIMs than AIRDs (OR: 1.8; 95% CI: 1.08, 3.2, P = 0.023) and HCs (OR: 4; 95% CI: 1.9, 8.1, P < 0.001), as well as more long-term safety concerns/fear (IIMs vs AIRDs – OR: 1.9; 95% CI: 1.2, 2.9, P = 0.001; IIMs vs HCs – OR: 5.4 95% CI: 3, 9.6, P < 0.001). Caucasians [OR 4.2 (1.7–10.3)] were likely to be more hesitant, while those with better PROMIS physical health score were less hesitant [OR 0.9 (0.8–0.97)].ConclusionVaccine hesitancy has decreased from 2021 to 2022, long-term safety concerns remain among patients with IIMs, particularly in Caucasians and those with poor physical function.
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  • Kanis, J A, et al. (författare)
  • Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.
  • 2023
  • Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Nature. - 1433-2965 .- 0937-941X. ; 34:12, s. 2027-2045
  • Tidskriftsartikel (refereegranskat)abstract
    • A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX.The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD).We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted β-coefficients.A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination.A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.
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  • Vandenput, L., et al. (författare)
  • A meta-analysis of previous falls and subsequent fracture risk in cohort studies
  • 2024
  • Ingår i: Osteoporosis International. - : Springer Nature. - 0937-941X .- 1433-2965. ; 35:3, s. 469-494
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary: The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. Introduction: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). Methods: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. Results: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33–1.51) and men (HR 1.53, 95% CI 1.41–1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27–1.84) in men vs. HR 1.32 (95% CI 1.20–1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. Conclusions: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction. 
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  • Vandenput, Liesbeth, 1974, et al. (författare)
  • Update of the fracture risk prediction tool FRAX : a systematic review of potential cohorts and analysis plan
  • 2022
  • Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 33:10, s. 2103-2136
  • Forskningsöversikt (refereegranskat)abstract
    • Summary: We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures.Introduction: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors.Methods: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible.Results: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed.Conclusions: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).
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  • Enerbäck, Sven, 1958, et al. (författare)
  • Acidosis and Deafness in Patients with Recessive Mutations in FOXI1
  • 2018
  • Ingår i: Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1046-6673 .- 1533-3450. ; 29:3, s. 1041-1048
  • Tidskriftsartikel (refereegranskat)abstract
    • Maintenance of the composition of inner ear fluid and regulation of electrolytes and acid-base homeostasis in the collecting duct system of the kidney require an overlapping set of membrane transport proteins regulated by the forkhead transcription factor FOXI1. In two unrelated consanguineous families, we identified three patients with novel homozygous missense mutations in FOXI1 (p.L146F and p.R213P) predicted to affect the highly conserved DNA binding domain. Patients presented with early-onset sensorineural deafness and distal renal tubular acidosis. In cultured cells, the mutations reduced the DNA binding affinity of FOXI1, which hence, failed to adequately activate genes crucial for normal inner ear function and acid base regulation in the kidney. A substantial proportion of patients with a clinical diagnosis of inherited distal renal tubular acidosis has no identified causative mutations in currently known disease genes. Our data suggest that recessive mutations in FOXI1 can explain the disease in a subset of these patients.
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  • Gupta, L., et al. (författare)
  • COVID-19 SEVERITY AND VACCINE BREAKTHROUGH INFECTIONS IN IDIOPATHIC INFLAMMATORY MYOPATHIES, OTHER SYSTEMIC AUTOIMMUNE AND INFLAMMATORY DISEASES, AND HEALTHY INDIVIDUALS : RESULTS FROM THE COVID-19 VACCINATION IN AUTOIMMUNE DISEASES (COVAD) STUDY.
  • 2022
  • Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 81:Suppl. 1, s. 334-336
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Significant gaps are present in the evidence of the spectrum and severity of COVID-19 infection in idiopathic inflammatory myopathies (IIM). IIM patients typically require immunosuppressive therapy, may have multiple disease sequelae, and frequent comorbidities, and thus may be more susceptible to severe COVID-19 infection and complications (1). The possibility of attenuated immunogenicity and reduced efficacy of COVID-19 vaccines due to concomitant immunosuppressive medication is a major concern in these patients, and there is little data available on COVID-19 vaccine breakthrough infections (BI) in IIM (2).ObjectivesThis study aimed to compare disease spectrum and severity and COVID-19 BI in patients with IIM, other systemic autoimmune and inflammatory diseases (SAIDs) and healthy controls (HCs).MethodsWe developed an extensive self-reporting electronic-survey (COVAD survey) featuring 36 questions to collect respondent demographics, SAID details, COVID-19 infection history, COVID-19 vaccination details, 7-day post vaccination adverse events and patient reported outcome measures using the PROMIS tool. After pilot testing, validation, translation into 18 languages on the online platform surveymonkey.com, and vetting by international experts, the COVAD survey was circulated in early 2021 by a multicenter study group of >110 collaborators in 94 countries. BI was defined as COVID-19 infection occurring more than 2 weeks after receiving 1st or 2nd dose of a COVID-19 vaccine. We analyzed data from the baseline survey for descriptive and intergroup comparative statistics based on data distribution and variable type.Results10900 respondents [mean age 42 (30-55) years, 74% females and 45% Caucasians] were analyzed. 1,227 (11.2%) had IIM, 4,640 (42.6%) had other SAIDs, and 5,033 (46.2%) were HC. All respondents included in the final analysis had received a single dose of the vaccine and 69% had received 2 primary doses. Pfizer (39.8%) was the most common vaccine received, followed by Oxford/AstraZeneca (13.4%), and Covishield (10.9%). IIM patients were older, had a higher Caucasian representation and higher Pfizer uptake than other SAIDs, and HC. A higher proportion of IIM patients received immunosuppressants than other SAIDs.IIMs were at a lower risk of symptomatic pre-vaccination COVID-19 infection compared to SAIDs [multivariate OR 0.6 (0.4-0.8)] and HCs [multivariate OR 0.39 (0.28-0.54)], yet at a higher risk of hospitalization due to COVID-19 compared to SAIDs [univariate OR 2.3 (1.2-3.5)] and HCs [multivariate OR 2.5 (1.1-5.8)]. BIs were very uncommon in IIM patients, with only 17 (1.4%) reporting BI. IIM patients were at a higher risk of contracting COVID-19 prior to vaccination than ≤2 weeks of vaccination [univariate OR 8 (4.1-15)] or BI [univariate OR 4.6 (2.7-8.0)]. BIs were equally severe compared to when they occurred prior to vaccination in IIMs, and were comparable between IIM, SAIDs, and HC (Figure 1), though BI disease duration was shorter in IIMs than SAIDs (7 vs 11 days, p 0.027). 13/17 IIM patients with BI were on immunosuppressants.ConclusionIIM patients experienced COVID-19 infection less frequently prior to vaccination but were at a higher risk of hospitalization and requirement for oxygen therapy compared with patients with HC. Breakthrough COVID-19 infections were rare (1.4%) in vaccinated IIM patients, and were similar to HC and SAIDs, except for shorter disease duration in IIM.References[1]Brito-Zerón P, Sisó-Almirall A, Flores-Chavez A, Retamozo S, Ramos-Casals M. SARS-CoV-2 infection in patients with systemic autoimmune diseases. Clin Exp Rheumatol. 2021 Jun;39(3):676–87.[2]Wack S, Patton T, Ferris LK. COVID-19 vaccine safety and efficacy in patients with immune-mediated inflammatory disease: Review of available evidence. J Am Acad Dermatol. 2021 Nov;85(5):1274–84.AcknowledgementsThe authors thank all members of the COVAD study group for their invaluable role in the collection of data. The authors thank all respondents for filling the questionnaire. The authors thank The Myositis Association, Myositis India, Myositis UK, the Myositis Global Network, Cure JM, Cure IBM, Sjögren’s India Foundation, EULAR PARE, and various other patient support groups and organizations for their invaluable contribution in the dissemination of this survey among patients which made the data collection possible. The authors also thank all members of the COVAD study group.Disclosure of InterestsLatika Gupta: None declared, Leonardo Santos Hoff: None declared, Naveen R: None declared, Parikshit Sen: None declared, Samuel Katsuyuki Shinjo: None declared, Jessica Day Grant/research support from: JD has received research funding from CSL Limited, James B. Lilleker: None declared, Vishwesh Agarwal: None declared, Sinan Kardes: None declared, Minchul Kim: None declared, Ashima Makol: None declared, Marcin Milchert: None declared, Tamer A Gheita: None declared, Babur Salim: None declared, Tsvetelina Velikova: None declared, Abraham Edgar Gracia-Ramos: None declared, Ioannis Parodis Speakers bureau: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Consultant of: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Grant/research support from: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Albert Selva-O’Callaghan: None declared, Elena Nikiphorou Speakers bureau: EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly, Consultant of: EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly, Grant/research support from: EN holds research grants from Pfizer and Lilly., Tulika Chatterjee: None declared, Ai Lyn Tan Speakers bureau: ALT has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB., Consultant of: ALT has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB., Arvind Nune: None declared, Lorenzo Cavagna: None declared, Miguel A Saavedra: None declared, Nelly Ziade Speakers bureau: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript, Consultant of: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript, Grant/research support from: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript, Johannes Knitza: None declared, Masataka Kuwana: None declared, Oliver Distler Speakers bureau: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Consultant of: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Hector Chinoy Speakers bureau: HC has been a speaker for UCB, Biogen., Consultant of: HC has received consulting fees from Novartis, Eli Lilly, Orphazyme, Astra Zeneca, Grant/research support from: HC has received grant support from Eli Lilly and UCB, Vikas Agarwal: None declared, Rohit Aggarwal Consultant of: RA has/had a consultancy relationship with and/or has received research funding from the following companies-Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, and Abbvie, Janssen, Alexion, Argenx, Q32
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  • Kvaerner, A. S., et al. (författare)
  • The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants
  • 2021
  • Ingår i: Bmc Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods: The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion: The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.
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31.
  • Palmer, Elizabeth E., et al. (författare)
  • Functional and clinical studies reveal pathophysiological complexity of CLCN4-related neurodevelopmental condition
  • 2023
  • Ingår i: Molecular Psychiatry. - : SPRINGERNATURE. - 1359-4184 .- 1476-5578. ; 28:2, s. 668-697
  • Tidskriftsartikel (refereegranskat)abstract
    • Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a "shift" of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis.
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32.
  • Sabel, Magnus, 1966, et al. (författare)
  • Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study
  • 2016
  • Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 129:3, s. 515-524
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2016 The Author(s)The HIT-SIOP-PNET4 randomised trial for standard risk medulloblastoma (MB) (2001–2006) included 338 patients and compared hyperfractionated and conventional radiotherapy. We here report the long-term outcome after a median follow up of 7.8 years, including detailed information on relapse and the treatment of relapse. Data were extracted from the HIT Group Relapsed MB database and by way of a specific case report form. The event-free and overall (OS) survival at 10 years were 76 ± 2 % and 78 ± 2 % respectively with no significant difference between the treatment arms. Seventy-two relapses and three second malignant neoplasms were reported. Thirteen relapses (18 %) were isolated local relapses in the posterior fossa (PF) and 59 (82 %) were craniospinal, metastatic relapses (isolated or multiple) with or without concurrent PF disease. Isolated PF relapse vs all other relapses occurred at mean/median of 38/35 and 28/26 months respectively (p = 0.24). Late relapse, i.e. >5 years from diagnosis, occurred in six patients (8 %). Relapse treatment consisted of combinations of surgery (25 %), focal radiotherapy (RT 22 %), high dose chemotherapy with stem cell rescue (HDSCR 21 %) and conventional chemotherapy (90 %). OS at 5 years after relapse was 6.0 ± 4 %. In multivariate analysis; isolated relapse in PF, and surgery were significantly associated with prolonged survival whereas RT and HDSCR were not. Survival after relapse was not related to biological factors and was very poor despite several patients receiving intensive treatments. Exploration of new drugs is warranted, preferably based on tumour biology from biopsy of the relapsed tumour.
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33.
  • Sieberts, SK, et al. (författare)
  • Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis
  • 2016
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 12460-
  • Tidskriftsartikel (refereegranskat)abstract
    • Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h2=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data.
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34.
  • Tobin, John J., et al. (författare)
  • The VLA/ALMA Nascent Disk and Multiplicity (VANDAM) Survey of Orion Protostars. II. A Statistical Characterization of Class 0 and Class i Protostellar Disks
  • 2020
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 890:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We have conducted a survey of 328 protostars in the Orion molecular clouds with the Atacama Large Millimeter/submillimeter Array at 0.87 mm at a resolution of ∼0.″1 (40 au), including observations with the Very Large Array at 9 mm toward 148 protostars at a resolution of ∼0.″08 (32 au). This is the largest multiwavelength survey of protostars at this resolution by an order of magnitude. We use the dust continuum emission at 0.87 and 9 mm to measure the dust disk radii and masses toward the Class 0, Class I, and flat-spectrum protostars, characterizing the evolution of these disk properties in the protostellar phase. The mean dust disk radii for the Class 0, Class I, and flat-spectrum protostars are 44.9-3.4+5.8, 37.0-3.0+4.9, and 28.5-2.3+3.7 au, respectively, and the mean protostellar dust disk masses are 25.9-4.0+7.7, 14.9-2.2+3.8, 11.6-1.9+3.5 M⊙, respectively. The decrease in dust disk masses is expected from disk evolution and accretion, but the decrease in disk radii may point to the initial conditions of star formation not leading to the systematic growth of disk radii or that radial drift is keeping the dust disk sizes small. At least 146 protostellar disks (35% of 379 detected 0.87 mm continuum sources plus 42 nondetections) have disk radii greater than 50 au in our sample. These properties are not found to vary significantly between different regions within Orion. The protostellar dust disk mass distributions are systematically larger than those of Class II disks by a factor of >4, providing evidence that the cores of giant planets may need to at least begin their formation during the protostellar phase.
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35.
  • Tomas, C, et al. (författare)
  • Autosomal SNP typing of forensic samples with the GenPlex (TM) HID System: Results of a collaborative study
  • 2011
  • Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 5:5, s. 369-375
  • Tidskriftsartikel (refereegranskat)abstract
    • The GenPlex (TM) HID System (Applied Biosystems - AB) offers typing of 48 of the 52 SNPforID SNPs and amelogenin. Previous studies have shown a high reproducibility of the GenPlex (TM) HID System using 250500 pg DNA of good quality. An international exercise was performed by 14 laboratories (9 in Europe and 5 in the US) in order to test the robustness and reliability of the GenPlex (TM) HID System on forensic samples. Three samples with partly degraded DNA and 10 samples with low amounts of DNA were analyzed in duplicates using various amounts of DNA. In order to compare the performance of the GenPlex (TM) HID System with the most commonly used STR kits, 500 pg of partly degraded DNA from three samples was typed by the laboratories using one or more STR kits. The median SNP typing success rate was 92.3% with 500 pg of partly degraded DNA. Three of the fourteen laboratories counted for more than two thirds of the locus dropouts. The median percentage of discrepant results was 0.2% with 500 pg degraded DNA. An increasing percentage of locus dropouts and discrepant results were observed when lower amounts of DNA were used. Different success rates were observed for the various SNPs. The rs763869 SNP was the least successful. With the exception of the MiniFiler (TM) kit (AB), GenPlex (TM) HID performed better than five other tested STR kits. When partly degraded DNA was analyzed, GenPlex (TM) HID showed a very low mean mach probability, while all STR kits except MiniFiler (TM) had very limited discriminatory power.
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36.
  • Camara-Costa, H., et al. (författare)
  • Quality of survival and cognitive performance in children treated for medulloblastoma in the PNET 4 randomized controlled trial
  • 2017
  • Ingår i: Neuro-Oncology Practice. - : Oxford University Press (OUP). - 2054-2577 .- 2054-2585. ; 4:3, s. 161-170
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. The relationship between direct assessments of cognitive performance and questionnaires assessing quality of survival (QoS) is reported to be weak-to-nonexistent. Conversely, the associations between questionnaires evaluating distinct domains of QoS tend to be strong. This pattern remains understudied. Methods. In the HIT-SIOP PNET4 randomized controlled trial, cognitive assessments, including Full Scale, Verbal and Performance IQ, Working Memory, and Processing Speed, were undertaken in 137 survivors of standard-risk medulloblastoma from 4 European countries. QoS questionnaires, including self-reports and/or parent reports of the Behavior Rating Inventory of Executive Function (BRIEF), the Health Utilities Index, the Strengths and Difficulties Questionnaire, and the Pediatric Quality of Life Inventory, were completed for 151 survivors. Correlations among direct cognitive assessments, QoS questionnaires, and clinical data were examined in participants with both assessments available (n = 86). Results. Correlations between direct measures of cognitive performance and QoS questionnaires were weak, except for moderate correlations between the BRIEF Metacognition Index (parent report) and working memory (r = .32) and between health status (self-report) and cognitive outcomes (r = .35-.44). Correlations among QoS questionnaires were moderate to strong both for parent and self-report (r = .39-.76). Principal Component Analysis demonstrated that questionnaires and cognitive assessments loaded on 2 separate factors. Conclusions. We hypothesize that the strong correlations among QoS questionnaires is partially attributable to the positive/negative polarity of all questions on the questionnaires, coupled with the relative absence of diseasespecific questions. These factors may be influenced by respondents' personality and emotional characteristics, unlike direct assessments of cognitive functioning, and should be taken into account in clinical trials.
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40.
  • Hoff, D., et al. (författare)
  • Quantum Beat Spectroscopy of Helium Photoelectrons
  • 2023
  • Ingår i: 2023 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference, CLEO/Europe-EQEC 2023. - 9798350345995
  • Konferensbidrag (refereegranskat)abstract
    • The availability of broadband extreme ultraviolet light sources allows for investigation of electron wave-packets from high lying bound states in atoms [1,2]. The dynamics of these states can be mapped out in the ionization continuum with an overlapping infrared field, which may also uncover new, light induced, dressed states [3]. Here, we carry out a complete characterization of these electron wave-packets using a small number of attosecond pulses.
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41.
  • Hoff, Erik, et al. (författare)
  • Carbonic anhydrase, obstructive sleep apnea and hypertension: Effects of intervention
  • 2020
  • Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 29:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Whole blood carbonic anhydrase activity (CAa) is increased in patients with obstructive sleep apnea (OSA). Our study investigated the influence of positive airway pressure (PAP) or CA inhibitor acetazolamide (ACT) therapy on CAa, OSA and blood pressure. Thirty‐three OSA patients (21 hypertensive, body mass index (BMI) 37 ± 7 kg/m2 and apnea–hypopnea index (AHI) of 47 ± 31 events/hr) were followed‐up after PAP treatment (compliance, 4.7 ± 1.5 hr/day; duration, median 6 [IQR 6,6] months) (Cohort A). A second OSA Cohort (B) contained nine hypertensive patients (BMI, 29 ± 4 kg/m2; AHI, 39 ± 20 events/hr) with 2‐week treatment of ACT, PAP or ACT + PAP in an open crossover study. CAa was assessed at baseline and at the end of each treatment period. In Cohort A, baseline CAa was higher in hypertensive, compared with normotensive, patients (1,033 ± 204 versus 861 ± 201 units, p = .028). PAP treatment reduced systolic/diastolic blood pressure but not CAa (−9 ± 11/−5 ± 7 mmHg and −20 ± 289 units, p < .001, <.001 and .70). In Cohort B, blood pressure was reduced in both ACT‐treated groups (−10 ± 10/−5 ± 7 mmHg, p = .043 and .019; and −5 ± 5/−13 ± 13 mmHg, p < .001 and .009). AHI was reduced in both groups: ACT only, −17 ± 9 events/hr p = .001; and ACT + PAP, −39 ± 19 events/hr, p < .001. PAP did not change CAa (p = .98) but activity tended to decrease after ACT with or without PAP (p = .081 and .056). CAa is elevated in hypertensive OSA patients. Long‐term PAP reduced blood pressure without affecting CAa. ACT reduced blood pressure and CAa. Increased CAa may constitute a physiological characteristic in OSA, contributing to comorbid hypertension.
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42.
  • Olaizola, B., et al. (författare)
  • High-sensitivity study of levels in Al-30 following beta decay of Mg-30
  • 2016
  • Ingår i: PHYSICAL REVIEW C. - 2469-9985 .- 2469-9993. ; 94:5
  • Tidskriftsartikel (refereegranskat)abstract
    • gamma-ray and fast-timing spectroscopy were used to study levels in Al-30 populated following the beta(-) decay of Mg-30. Five new transitions and three new levels were located in Al-30. A search was made to identify the third 1(+) state expected at an excitation energy of similar to 2.5 MeV. Two new levels were found, at 3163.9 and 3362.5 keV, that are firm candidates for this state. Using the advanced time-delayed (ATD) beta gamma gamma (t) method we have measured the lifetime of the 243.8-keV state to be T-1/2 = 15(4) ps, which implies that the 243.8-keV transition is mainly of M1 character. Its fast B(M1; 2(+) -> 3(+)) value of 0.10(3) W.u. is in very good agreement with the USD shell-model prediction of 0.090 W.u. The 1801.5-keV level is the only level observed in this study that could be a candidate for the second excited 2(+) state.
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43.
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44.
  • Schmoll, H. J., et al. (författare)
  • ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making
  • 2012
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 23:10, s. 2479-2516
  • Tidskriftsartikel (refereegranskat)abstract
    • Colorectal cancer (CRC) is the most common tumour type in both sexes combined in Western countries. Although screening programmes including the implementation of faecal occult blood test and colonoscopy might be able to reduce mortality by removing precursor lesions and by making diagnosis at an earlier stage, the burden of disease and mortality is still high. Improvement of diagnostic and treatment options increased staging accuracy, functional outcome for early stages as well as survival. Although high quality surgery is still the mainstay of curative treatment, the management of CRC must be a multi-modal approach performed by an experienced multi-disciplinary expert team. Optimal choice of the individual treatment modality according to disease localization and extent, tumour biology and patient factors is able to maintain quality of life, enables long-term survival and even cure in selected patients by a combination of chemotherapy and surgery. Treatment decisions must be based on the available evidence, which has been the basis for this consensus conference-based guideline delivering a clear proposal for diagnostic and treatment measures in each stage of rectal and colon cancer and the individual clinical situations. This ESMO guideline is recommended to be used as the basis for treatment and management decisions.
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45.
  • Taquet, V., et al. (författare)
  • Linking interstellar and cometary O2: A deep search for 16O18O in the solar-Type protostar IRAS 16293b-2422
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 618
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent measurements carried out at comet 67P/Churyumov-Gerasimenko (67P) with the Rosetta probe revealed that molecular oxygen, O2, is the fourth most abundant molecule in comets. Models show that O2 is likely of primordial nature, coming from the interstellar cloud from which our solar system was formed. However, gaseous O2 is an elusive molecule in the interstellar medium with only one detection towards quiescent molecular clouds, in the ρ Oph A core. We perform a deep search for molecular oxygen, through the 21-01 rotational transition at 234 GHz of its 16O18O isotopologue, towards the warm compact gas surrounding the nearby Class 0 protostar IRAS 16293-2422 B with the ALMA interferometer. We also look for the chemical daughters of O2, HO2, and H2O2. Unfortunately, the H2O2 rotational transition is dominated by ethylene oxide c-C2H4O while HO2 is not detected. The targeted 16O18O transition is surrounded by two brighter transitions at ± 1 km s-1 relative to the expected 16O18O transition frequency. After subtraction of these two transitions, residual emission at a 3σ level remains, but with a velocity offset of 0.3-0.5 km s-1 relative to the source velocity, rendering the detection "tentative". We derive the O2 column density for two excitation temperatures Tex of 125 and 300 K, as indicated by other molecules, in order to compare the O2 abundance between IRAS 16293 and comet 67P. Assuming that 16O18O is not detected and using methanol CH3OH as a reference species, we obtain a [O2]/[CH3OH] abundance ratio lower than 2-5, depending on the assumed Tex, a three to four times lower abundance than the [O2]/[CH3OH] ratio of 5-15 found in comet 67P. Such a low O2 abundance could be explained by the lower temperature of the dense cloud precursor of IRAS 16293 with respect to the one at the origin of our solar system that prevented efficient formation of O2 in interstellar ices.
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46.
  • Tobin, John J., et al. (författare)
  • The VLA/ALMA Nascent Disk and Multiplicity (VANDAM) Survey of Orion Protostars. I. Identifying and Characterizing the Protostellar Content of the OMC-2 FIR4 and OMC-2 FIR3 Regions
  • 2019
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 886:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present Atacama Large Millimeter/submillimeter Array (0.87 mm) and Very Large Array (9 mm) observations toward OMC-2 FIR4 and OMC-2 FIR3 within the Orion integral-shaped filament, thought to be two of the nearest regions of intermediate-mass star formation. We characterize the continuum sources within these regions on ?40 au (01) scales and associated molecular line emission at a factor of ?30 better resolution than previous observations at similar wavelengths. We identify six compact continuum sources within OMC-2 FIR4, four in OMC-2 FIR3, and one additional source just outside OMC-2 FIR4. This continuum emission is tracing the inner envelope and/or disk emission on less than 100 au scales. HOPS-108 is the only protostar in OMC-2 FIR4 that exhibits emission from high-excitation transitions of complex organic molecules (e.g., methanol and other lines) coincident with the continuum emission. HOPS-370 in OMC-2 FIR3, with L;?;360 L, also exhibits emission from high-excitation methanol and other lines. The methanol emission toward these two protostars is indicative of temperatures high enough to thermally evaporate it from icy dust grains; overall, these protostars have characteristics similar to hot corinos. We do not identify a clear outflow from HOPS-108 in (CO)-C-12, but we find evidence of interaction between the outflow/jet from HOPS-370 and the OMC-2 FIR4 region. A multitude of observational constraints indicate that HOPS-108 is likely a low- to intermediate-mass protostar in its main mass accretion phase and is the most luminous protostar in OMC-2 FIR4. The high-resolution data presented here are essential for disentangling the embedded protostars from their surrounding dusty environments and characterizing them.
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47.
  • Verslype, C., et al. (författare)
  • The management of pancreatic cancer. Current expert opinion and recommendations derived from the 8th World Congress on Gastrointestinal Cancer, Barcelona, 2006
  • 2007
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:Suppl. 7, s. VII1-VII10
  • Tidskriftsartikel (refereegranskat)abstract
    • This article summarizes the expert discussion on the management of pancreatic cancer, which took place during the 8th World Congress on Gastrointestinal Cancer in June 2006 in Barcelona. A multidisciplinary approach to a patient with pancreatic cancer is essential, in order to guarantee an optimal staging, surgery, selection of the appropriate (neo-)adjuvant strategy and chemotherapeutic choice management. Moreover, optimal symptomatic management requires a dedicated team of health care professionals. Quality control of surgery and pathology is especially important in this disease with a high locoregional failure rate. There is now solid evidence in favour of chemotherapy in both the adjuvant and palliative setting, and gemcitabine combined with erlotinib, capecitabine or platinum compounds seems to be slightly more active than gemcitabine alone in advanced pancreatic cancer. There is a place for chemoradiotherapy in selected patients with locally advanced disease, while the role in the adjuvant setting remains controversial. Those involved in the care for patients with pancreatic cancer should be encouraged to participate in well-designed clinical trials, in order to increase the evidence-based knowledge and to make further progress.
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