1. |
- Aad, G., et al.
(author)
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- 2012
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swepub:Mat__t (peer-reviewed)
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2. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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3. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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5. |
- Bouyoucef, S E, et al.
(author)
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Poster Session 2 : Monday 4 May 2015, 08
- 2015
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In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Journal article (peer-reviewed)
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6. |
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7. |
- Thoma, B, et al.
(author)
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An international, interprofessional investigation of the self-reported podcast listening habits of emergency clinicians: A METRIQ Study
- 2020
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In: CJEM. - : Springer Science and Business Media LLC. - 1481-8043 .- 1481-8035. ; 22:1, s. 112-117
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Journal article (peer-reviewed)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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9. |
- Waszak, S. M., et al.
(author)
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Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort
- 2018
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In: Lancet Oncology. - : Elsevier BV. - 1470-2045. ; 19:6, s. 785-798
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Journal article (peer-reviewed)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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10. |
- Kanis, J A, et al.
(author)
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Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.
- 2023
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In: 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
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Journal article (peer-reviewed)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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11. |
- Vandenput, L., et al.
(author)
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A meta-analysis of previous falls and subsequent fracture risk in cohort studies
- 2024
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In: Osteoporosis International. - : Springer Nature. - 0937-941X .- 1433-2965. ; 35:3, s. 469-494
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Journal article (peer-reviewed)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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12. |
- Vandenput, Liesbeth, 1974, et al.
(author)
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Update of the fracture risk prediction tool FRAX : a systematic review of potential cohorts and analysis plan
- 2022
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In: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 33:10, s. 2103-2136
-
Research review (peer-reviewed)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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19. |
- Tomas, C, et al.
(author)
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Autosomal SNP typing of forensic samples with the GenPlex (TM) HID System: Results of a collaborative study
- 2011
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In: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 5:5, s. 369-375
-
Journal article (peer-reviewed)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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21. |
- Sieberts, SK, et al.
(author)
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Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis
- 2016
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 12460-
-
Journal article (peer-reviewed)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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22. |
- Verslype, C., et al.
(author)
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The management of pancreatic cancer. Current expert opinion and recommendations derived from the 8th World Congress on Gastrointestinal Cancer, Barcelona, 2006
- 2007
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:Suppl. 7, s. VII1-VII10
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Journal article (peer-reviewed)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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25. |
- Camara-Costa, H., et al.
(author)
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Quality of survival and cognitive performance in children treated for medulloblastoma in the PNET 4 randomized controlled trial
- 2017
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In: Neuro-Oncology Practice. - : Oxford University Press (OUP). - 2054-2577 .- 2054-2585. ; 4:3, s. 161-170
-
Journal article (peer-reviewed)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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26. |
- Folke, Carl, et al.
(author)
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Our future in the Anthropocene biosphere
- 2021
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In: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 50:4, s. 834-869
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Journal article (peer-reviewed)abstract
- The COVID-19 pandemic has exposed an interconnected and tightly coupled globalized world in rapid change. This article sets the scientific stage for understanding and responding to such change for global sustainability and resilient societies. We provide a systemic overview of the current situation where people and nature are dynamically intertwined and embedded in the biosphere, placing shocks and extreme events as part of this dynamic; humanity has become the major force in shaping the future of the Earth system as a whole; and the scale and pace of the human dimension have caused climate change, rapid loss of biodiversity, growing inequalities, and loss of resilience to deal with uncertainty and surprise. Taken together, human actions are challenging the biosphere foundation for a prosperous development of civilizations. The Anthropocene reality-of rising system-wide turbulence-calls for transformative change towards sustainable futures. Emerging technologies, social innovations, broader shifts in cultural repertoires, as well as a diverse portfolio of active stewardship of human actions in support of a resilient biosphere are highlighted as essential parts of such transformations.
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27. |
- Hoff, D., et al.
(author)
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Direct CEP Stabilization of a high-repetition rate, few-cycle OPCPA chain with a single feedback loop, employing a Stereo-ATI
- 2023
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In: 2023 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference, CLEO/Europe-EQEC 2023. - 9798350345995
-
Conference paper (peer-reviewed)abstract
- Today's Carrier-Envelope Phase (CEP) stabilizations of mode-locked oscillators widely used in attosecond science and frequency metrology rely on octave spanning frequency combs and the detection of beating between the blue end and the frequency doubled red end of the same spectrum. This technique was established by the seminal works of Hänsch and co-workers [1], demonstrating the stabilization of optical frequencies from such a frequency comb by transferring the slippage of the CEP (or carrier-envelope offset frequency) into a detectable radio frequency by f-2f interferometry. The requirement of an octave spanning spectrum means that usually some kind of super-continuum generation is involved, which, in practice often is a fragile scheme since wide band oscillators are very prone to instabilities and noise.
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28. |
- Hoff, D., et al.
(author)
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Quantum Beat Spectroscopy of Helium Photoelectrons
- 2023
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In: 2023 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference, CLEO/Europe-EQEC 2023. - 9798350345995
-
Conference paper (peer-reviewed)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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30. |
- Maxwell, Christopher A., et al.
(author)
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Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
- 2011
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In: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
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Journal article (peer-reviewed)abstract
- Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
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32. |
- Schlaepfer, T E, et al.
(author)
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Vagus nerve stimulation for depression: Efficacy and safety in a European study.
- 2008
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In: Psychological Medicine. - 0033-2917 .- 1469-8978. ; 38:5, s. 651-661
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Journal article (peer-reviewed)abstract
- Background: Vagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few side-effects, for intractable depression. Method: An open, uncontrolled European multi-centre study (D03) of VNS therapy was conducted, in addition to stable pharmacotherapy, in 74 patients with treatment-resistant depression (TRD). Treatment remained unchanged for the first 3 months; in the subsequent 9 months, medications and VNS dosing parameters were altered as indicated clinically. Results: The baseline 28-item Hamilton Depression Rating Scale (HAMD-28) score averaged 34. After 3 months of VNS, response rates (≥50% reduction in baseline scores) reached 37% and remission rates (HAMD-28 score <10) 17%. Response rates increased to 53% after 1 year of VNS, and remission rates reached 33%. Response was defined as sustained if no relapse occurred during the first year of VNS after response onset; 44% of patients met these criteria. Median time to response was 9 months. Most frequent side-effects were voice alteration (63% at 3 months of stimulation) and coughing (23%). Conclusions: VNS therapy was effective in reducing severity of depression; efficacy increased over time. Efficacy ratings were in the same range as those previously reported from a USA study using a similar protocol; at 12 months, reduction of symptom severity was significantly higher in the European sample. This might be explained by a small but significant difference in the baseline HAMD-28 score and the lower number of treatments in the current episode in the European study.
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33. |
- Schmoll, H. J., et al.
(author)
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ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making
- 2012
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 23:10, s. 2479-2516
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Journal article (peer-reviewed)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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36. |
- Taquet, V., et al.
(author)
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Linking interstellar and cometary O2: A deep search for 16O18O in the solar-Type protostar IRAS 16293b-2422
- 2018
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 618
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Journal article (peer-reviewed)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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37. |
- Vandenput, Liesbeth, et al.
(author)
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A meta-analysis of previous falls and subsequent fracture risk in cohort studies
- 2024
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In: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 35:3, s. 469-494
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Journal article (peer-reviewed)abstract
- SummaryThe 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.IntroductionPrevious 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).MethodsThe 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.ResultsFalls 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.ConclusionsA 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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- Botteri, Edoardo, et al.
(author)
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Changes in lifestyle and risk of colorectal cancer in the european prospective investigation into cancer and nutrition
- 2023
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In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 118:4, s. 702-711
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Journal article (peer-reviewed)abstract
- Introduction: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multicountry European cohort.Methods: We used baseline and follow-up questionnaire data from the European Prospective Investigation into Cancer cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index, and physical activity collected at the 2 time points. HLI ranged from 0 (most unfavorable) to 16 (most favorable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI).Results: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. The median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI > 11), those in the bottom tertile at follow-up (HLI ≤ 9) had a higher CRC risk (HR 1.34; 95% CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95% CI 0.59-1.00) than those remaining in the bottom tertile.Discussion: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.
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- Botteri, Edoardo, et al.
(author)
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Lifestyle changes in middle age and risk of cancer : evidence from the European Prospective Investigation into Cancer and Nutrition
- 2024
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In: European Journal of Epidemiology. - 0393-2990. ; 39:2, s. 147-159
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Journal article (peer-reviewed)abstract
- In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption, body mass index and physical activity. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI change and risk of lifestyle-related cancers—including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others—using Cox regression models. We reported hazard ratios (HR) with 95% confidence intervals (CI). Median time between the two questionnaires was 5.7 years, median age at follow-up questionnaire was 59 years. After the follow-up questionnaire, we observed 14,933 lifestyle-related cancers over a median follow-up of 7.8 years. Each unit increase in the HLI score was associated with 4% lower risk of lifestyle-related cancers (HR 0.96; 95%CI 0.95–0.97). Among participants in the top HLI third at baseline (HLI > 11), those in the bottom third at follow-up (HLI ≤ 9) had 21% higher risk of lifestyle-related cancers (HR 1.21; 95%CI 1.07–1.37) than those remaining in the top third. Among participants in the bottom HLI third at baseline, those in the top third at follow-up had 25% lower risk of lifestyle-related cancers (HR 0.75; 95%CI 0.65–0.86) than those remaining in the bottom third. These results indicate that lifestyle changes in middle age may have a significant impact on cancer risk.
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- Brinkman, M J, et al.
(author)
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Decay from a superdeformed band in Pb-194
- 1996
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 53:4, s. R1461-R1464
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Journal article (peer-reviewed)abstract
- Three experiments using the (174) Yb(Mg-25,5n)Pb-194 reaction have been undertaken at the Early Implementation of Gammasphere to study the decay of known superdeformed states in Pb-194. A single discrete transition with an energy of 2.746(2) MeV carrying 6(2)% of the full superdeformed band intensity has been identified. A discussion of our results and the assignment of the 2.746-MeV transition as a discrete gamma ray directly connecting the superdeformed 8(+) and low-lying 6(+) levels will be presented.
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- Enerbäck, Sven, 1958, et al.
(author)
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Acidosis and Deafness in Patients with Recessive Mutations in FOXI1
- 2018
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In: Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1046-6673 .- 1533-3450. ; 29:3, s. 1041-1048
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Journal article (peer-reviewed)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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- Hedner, Jan A, 1953, et al.
(author)
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A Randomized Controlled Clinical Trial Exploring Safety and Tolerability of Sulthiame in Sleep Apnea
- 2022
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In: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 205:12, s. 1461-1469
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Journal article (peer-reviewed)abstract
- Rationale: Current therapies for obstructive sleep apnea (OSA) are limited by insufficient efficacy, compliance, or tolerability. An effective pharmacological treatment for OSA is warranted. Carbonic anhydrase inhibition has been shown to ameliorate OSA. Objectives: To explore safety and tolerability of the carbonic anhydrase inhibitor sulthiame (STM) in OSA. Methods: A 4-week double-blind, randomized, placebo-controlled dose-guiding trial was conducted in patients with moderate and/or severe OSA not tolerating positive airway pressure treatment. Measurements and Main Results: Intermittent paresthesia was reported by 79%, 67%, and 18% of patients receiving 400 mg STM (n = 34), 200 mg STM (n =12), and placebo (n = 22), respectively. Dyspnea was reported after 400 mg STM (18%). Six patients in the higher dose group withdrew because of adverse events. There were no serious adverse events. STM reduced the apnea-hypopnea index from 55.2 to 33.0 events/h (-41.0%) in the 400-mg group and from 61.1 to 40.6 events/h (-32.1%) after 200 mg (P < 0.001 for both). Corresponding placebo values were 53.9 and 50.9 events/h (-5.4%). The apnea-hypopnea index reduction threshold of >= 50% was reached in 40% of patients after 400 mg, 25% after 200 mg, and 5% after placebo. Mean overnight oxygen saturation improved by 1.1% after 400 and 200 mg (P < 0.001 and P = 0.034, respectively). Patient-related outcomes were unchanged. Conclusions: STM showed a satisfactory safety profile in moderate and/or severe OSA. STM reduced OSA, on average, by more than 20 events/h, one of the strongest reductions reported in a drug trial in OSA. Larger scale clinical studies of STM in OSA are justified.
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