| 1. |
- Hemingway, Harry, et al.
(författare)
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Big data from electronic health records for early and late translational cardiovascular research : challenges and potential
- 2018
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 39:16, s. 1481-1495
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Cohorts of millions of people's health records, whole genome sequencing, imaging, sensor, societal and publicly available data present a rapidly expanding digital trace of health. We aimed to critically review, for the first time, the challenges and potential of big data across early and late stages of translational cardiovascular disease research.Methods and results: We sought exemplars based on literature reviews and expertise across the BigData@Heart Consortium. We identified formidable challenges including: data quality, knowing what data exist, the legal and ethical framework for their use, data sharing, building and maintaining public trust, developing standards for defining disease, developing tools for scalable, replicable science and equipping the clinical and scientific work force with new inter-disciplinary skills. Opportunities claimed for big health record data include: richer profiles of health and disease from birth to death and from the molecular to the societal scale; accelerated understanding of disease causation and progression, discovery of new mechanisms and treatment-relevant disease sub-phenotypes, understanding health and diseases in whole populations and whole health systems and returning actionable feedback loops to improve (and potentially disrupt) existing models of research and care, with greater efficiency. In early translational research we identified exemplars including: discovery of fundamental biological processes e.g. linking exome sequences to lifelong electronic health records (EHR) (e.g. human knockout experiments); drug development: genomic approaches to drug target validation; precision medicine: e.g. DNA integrated into hospital EHR for pre-emptive pharmacogenomics. In late translational research we identified exemplars including: learning health systems with outcome trials integrated into clinical care; citizen driven health with 24/7 multi-parameter patient monitoring to improve outcomes and population-based linkages of multiple EHR sources for higher resolution clinical epidemiology and public health.Conclusion: High volumes of inherently diverse ('big') EHR data are beginning to disrupt the nature of cardiovascular research and care. Such big data have the potential to improve our understanding of disease causation and classification relevant for early translation and to contribute actionable analytics to improve health and healthcare.
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| 2. |
- Apweiler, Rolf, et al.
(författare)
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Approaching clinical proteomics : current state and future fields of application in cellular proteomics
- 2009
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Ingår i: Cytometry. Part A : the journal of the International Society for Analytical Cytology. - : Wiley. - 1552-4922. ; 75A:10, s. 816-832
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Forskningsöversikt (refereegranskat)abstract
- Recent developments in proteomics technology offer new opportunities for clinical applications in hospital or specialized laboratories including the identification of novel biomarkers, monitoring of disease, detecting adverse effects of drugs, and environmental hazards. Advanced spectrometry technologies and the development of new protein array formats have brought these analyses to a standard, which now has the potential to be used in clinical diagnostics. Besides standardization of methodologies and distribution of proteomic data into public databases, the nature of the human body fluid proteome with its high dynamic range in protein concentrations, its quantitation problems, and its extreme complexity present enormous challenges. Molecular cell biology (cytomics) with its link to proteomics is a new fast moving scientific field, which addresses functional cell analysis and bioinformatic approaches to search for novel cellular proteomic biomarkers or their release products into body fluids that provide better insight into the enormous biocomplexity of disease processes and are suitable for patient stratification, therapeutic monitoring, and prediction of prognosis. Experience from studies of in vitro diagnostics and especially in clinical chemistry showed that the majority of errors occurs in the preanalytical phase and the setup of the diagnostic strategy. This is also true for clinical proteomics where similar preanalytical variables such as inter- and intra-assay variability due to biological variations or proteolytical activities in the sample will most likely also influence the results of proteomics studies. However, before complex proteomic analysis can be introduced at a broader level into the clinic, standardization of the preanalytical phase including patient preparation, sample collection, sample preparation, sample storage, measurement, and data analysis is another issue which has to be improved. In this report, we discuss the recent advances and applications that fulfill the criteria for clinical proteomics with the focus on cellular proteomics (cytoproteomics) as related to preanalytical and analytical standardization and to quality control measures required for effective implementation of these technologies and analytes into routine laboratory testing to generate novel actionable health information. It will then be crucial to design and carry out clinical studies that can eventually identify novel clinical diagnostic strategies based on these techniques and validate their impact on clinical decision making.
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| 3. |
- Apweiler, Rolf, et al.
(författare)
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Approaching clinical proteomics : current state and future fields of application in fluid proteomics
- 2009
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 47:6, s. 724-744
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Forskningsöversikt (refereegranskat)abstract
- The field of clinical proteomics offers opportunities to identify new disease biomarkers in body fluids, cells and tissues. These biomarkers can be used in clinical applications for diagnosis, stratification of patients for specific treatment, or therapy monitoring. New protein array formats and improved spectrometry technologies have brought these analyses to a level with potential for use in clinical diagnostics. The nature of the human body fluid proteome with its large dynamic range of protein concentrations presents problems with quantitation. The extreme complexity of the proteome in body fluids presents enormous challenges and requires the establishment of standard operating procedures for handling of specimens, increasing sensitivity for detection and bioinformatical tools for distribution of proteomic data into the public domain. From studies of in vitro diagnostics, especially in clinical chemistry, it is evident that most errors occur in the preanalytical phase and during implementation of the diagnostic strategy. This is also true for clinical proteomics, and especially for fluid proteomics because of the multiple pretreatment processes. These processes include depletion of high-abundance proteins from plasma or enrichment processes for urine where biological variation or differences in proteolytic activities in the sample along with preanalytical variables such as inter- and intra-assay variability will likely influence the results of proteomics studies. However, before proteomic analysis can be introduced at a broader level into the clinical setting, standardization of the preanalytical phase including patient preparation, sample collection, sample preparation, sample storage, measurement and data analysis needs to be improved. In this review, we discuss the recent technological advances and applications that fulfil the criteria for clinical proteomics, with the focus on fluid proteomics. These advances relate to preanalytical factors, analytical standardization and quality-control measures required for effective implementation into routine laboratory testing in order to generate clinically useful information. With new disease biomarker candidates, it will be crucial to design and perform clinical studies that can identify novel diagnostic strategies based on these techniques, and to validate their impact on clinical decision-making.
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| 4. |
- Buylaert, J. -P, et al.
(författare)
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Luminescence dating of the PASADO core 5022-1D from Laguna Potrok Aike (Argentina) using IRSL signals from feldspar
- 2013
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 71, s. 70-80
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Tidskriftsartikel (refereegranskat)abstract
- We have measured and tested a luminescence chronology for the PASADO core 5022-1D from the maar lake of Laguna Potrok Aike. Because of unsuitable quartz OSL characteristics, sand-sized K-feldspar extracts were chosen as a dosimeter and the dose was measured using a post-IR IRSL (pIRIR(290)) measurement protocol. Using this approach we were able to access a stable signal and thus avoid the ubiquitous problem of feldspar signal instability. Extensive laboratory tests show that the chosen pIRIR(290) protocol is applicable to these samples. We also developed a new criterion based on known relative bleaching rates of the conventional IRSL signal (IR50) and the pIRIR(290) signal and the relationship between resulting equivalent doses; this is used to identify and reject poorly bleached samples. Eighteen samples out of 47 were rejected based on this criterion, without reference to absolute doses or stratigraphy; the resulting age-depth profile is self-consistent, increases smoothly with depth and is in agreement with independent age control based on volcanic ash layers (Reclus, Mt Burney and Hudson tephras) at the top and middle of the core. Our new luminescence chronology suggests that the 5022-1D core reaches back to similar to 65 ka at similar to 96 m below lake floor.
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| 5. |
- Göttel, Holger, et al.
(författare)
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Influence of changed vegetations fields on regional climate simulations in the Barents Sea Region
- 2008
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Ingår i: Climatic Change. - : Springer. - 0165-0009 .- 1573-1480. ; 87:1-2, s. 35-50
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Tidskriftsartikel (refereegranskat)abstract
- In the context of the EU-Project BALANCE (http://balance-eu.info) the regional climate model REMO was used for extensive calculations of the Barents Sea climate to investigate the vulnerability of this region to climate change. The regional climate model REMO simulated the climate change of the Barents Sea Region between 1961 and 2100 (Control and Climate Change run, CCC-Run). REMO on similar to 50 km horizontal resolution was driven by the transient ECHAM4/OPYC3 IPCC SRES B2 scenario. The output of the CCC-Run was applied to drive the dynamic vegetation model LPJ-GUESS. The results of the vegetation model were used to repeat the CCC-Run with dynamic vegetation fields. The feedback effect of the modified vegetation on the climate change signal is investigated and discussed with focus on precipitation, temperature and snow cover. The effect of the offline coupled vegetation feedback run is much lower than the greenhouse gas effect.
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| 6. |
- Kalman, Janos L, et al.
(författare)
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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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| 7. |
- Kehyayan, Aram, et al.
(författare)
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The effect of a visuospatial interference intervention on posttraumatic intrusions : a cross-over randomized controlled trial
- 2024
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Ingår i: European Journal of Psychotraumatology. - : Taylor & Francis. - 2000-8198 .- 2000-8066. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intrusive memories form a core symptom of Posttraumatic Stress Disorder (PTSD). Based on concepts of visuospatial interference and memory-updating accounts, technological innovations aim to attenuate such intrusions using visuospatial interventions.Objective: This study aims to test the effect of a visuospatial Tetris-based intervention versus a verbal condition (Wiki) and a never-targeted control (no intervention) on intrusion frequency.Method: A randomized crossover trial was conducted including N = 38 PTSD patients who had at least 3 distinct intrusive memories of trauma. After both 2 weeks (intervention 1) and 4 weeks (intervention 2), one of the three memories was randomly selected and either the visuospatial intervention (memory reminder of a traumatic memory + Tetris) or verbal condition (reading a Wikipedia article + answering questions) was performed on their first memory in randomized order. In the week 4 session, the patient conducted the other intervention condition on their second memory (crossover). The third memory was never targeted (no intervention). Daily occurrence of intrusions over 8 weeks was collected using a diary and analysed using mixed Poisson regression models.Results: Overall, there was no significant reduction in intrusion frequency from either intervention compared to each other, and to no intervention control (relative risk Tetris/Wiki: 0.947; p = .31; relative risk no intervention/Tetris: 1.060; p = .15; relative risk no intervention/Wiki: 1.004; p = .92).Conclusions: There was no effect of either intervention on intrusions when administered in a crossover design where participants received both interventions. Design shortcomings and consequences for future studies are discussed.
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| 8. |
- Kern, Ralph, et al.
(författare)
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Coulomb Excitation of Proton-rich N = 80 Isotones at HIE-ISOLDE
- 2020
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1555:1
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Tidskriftsartikel (refereegranskat)abstract
- A projectile Coulomb-excitation experiment was performed at the radioactive ion beam facility HIE-ISOLDE at CERN. The radioactive 140Nd and 142Sm ions were post accelerated to the energy of 4.62 MeV/A and impinged on a 1.45 mg/cm2-thin 208Pb target. The γ rays depopulating the Coulomb-excited states were recorded by the HPGe-array MINIBALL. The scattered charged particles were detected by a double-sided silicon strip detector in forward direction. Experimental γ-ray intensities were used for the determination of electromagnetic transition matrix elements. Preliminary results for the reduced transition strength of the B(M1 23+ to 21+)=0.35(19) μN2 of 140Nd and a first estimation for 142Sm have been deduced using the Coulomb-excitation calculation software GOSIA. The 23+ states of 140Nd and 142Sm show indications of being the main fragment of the proton-neutron mixed-symmetry 21, ms+ state.
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| 9. |
- Kern, Ralph, et al.
(författare)
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Search for Isovector Valence-Shell Excitations in 140Nd and 142Sm via Coulomb excitation reactions of radioactive ion beams
- 2018
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Ingår i: International Conference on Nuclear Structure and Related Topics (NSRT18). - : EDP Sciences. - 2101-6275. ; 194
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Konferensbidrag (refereegranskat)abstract
- Projectile Coulomb excitation experiments were performed at HIE-ISOLDE at CERN with the radioactive ion beams of 140Nd and 142Sm. Ions with an energy of 4:62 MeV/A were impinging on a 1.45 mg/cm2 thick 208Pb target. The γ-rays depopulating the Coulomb-excited states were recorded by the HPGe-array MINIBALL and scattered particles were detected by a double-sided silicon strip detector. Experimental intensities were used for the determination of electromagnetic transition matrix elements. A preliminary result of the B(M1; 2+ 3 → 2+ 1) of 140Nd and an upper limit for the case of 142Sm are revealing the main fragments of the proton-neutron mixed-symmetry 2+ 1;ms states.
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| 10. |
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