| 1. |
- Deijen, Charlotte L., et al.
(författare)
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Ten-year outcomes of a randomised trial of laparoscopic versus open surgery for colon cancer
- 2017
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Ingår i: Surgical Endoscopy. - : SPRINGER. - 0930-2794 .- 1432-2218. ; 31:6, s. 2607-2615
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Tidskriftsartikel (refereegranskat)abstract
- Laparoscopic surgery for colon cancer is associated with improved recovery and similar cancer outcomes at 3 and 5 years in comparison with open surgery. However, long-term survival rates have rarely been reported. Here, we present survival and recurrence rates of the Dutch patients included in the COlon cancer Laparoscopic or Open Resection (COLOR) trial at 10-year follow-up. Between March 1997 and March 2003, patients with non-metastatic colon cancer were recruited by 29 hospitals in eight countries and randomised to either laparoscopic or open surgery. Main inclusion criterion for the COLOR trial was solitary adenocarcinoma of the left or right colon. The primary outcome was disease-free survival at 3 years, and secondary outcomes included overall survival and recurrence. The 10-year follow-up data of all Dutch patients were collected. Analysis was by intention-to-treat. The trial was registered at ClinicalTrials.gov (NCT00387842). In total, 1248 patients were randomised, of which 329 were Dutch. Fifty-eight Dutch patients were excluded and 15 were lost to follow-up, leaving 256 patients for 10-year analysis. Median follow-up was 112 months. Disease-free survival rates were 45.2 % in the laparoscopic group and 43.2 % in the open group (difference 2.0 %; 95 % confidence interval (CI) -10.3 to 14.3; p = 0.96). Overall survival rates were 48.4 and 46.7 %, respectively (difference 1.7 %; 95 % CI -10.6 to 14.0; p = 0.83). Stage-specific analysis revealed similar survival rates for both groups. Sixty-two patients were diagnosed with recurrent disease, accounting for 29.4 % in the laparoscopic group and 28.2 % in the open group (difference 1.2 %; 95 % CI -11.1 to 13.5; p = 0.73). Seven patients had port- or wound-site recurrences (laparoscopic n = 3 vs. open n = 4). Laparoscopic surgery for non-metastatic colon cancer is associated with similar rates of disease-free survival, overall survival and recurrences as open surgery at 10-year follow-up.
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| 2. |
- Liu, Ming, et al.
(författare)
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Trigger algorithm development on FPGA-based Compute Nodes
- 2009
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Ingår i: 2009 16th IEEE-NPSS Real Time Conference. - New York : IEEE. - 9781424457960 ; , s. 478-484
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Konferensbidrag (refereegranskat)abstract
- Based on the ATCA computation architecture and Compute Nodes (CN), investigation and implementation work has been being executed for HADES and PANDA trigger algorithms. We present our designs for HADES track reconstruction processing, Cherenkov ring recognition, Time-Of-Flight processing, electromagnetic shower recognition.. and the PANDA straw tube tracking algorithm. They will appear as co-processors in the uniform system design to undertake the detector-specific computing. The algorithm principles will be explained and hardware designs are described in the paper. The current progress reveals the feasibility to implement these algorithms on FPGAs. Also experimental results demonstrate the performance speedup when compared to alternative software solutions, as well as the potential capability of high-speed parallel/pipelined processing in Data Acquisition and Trigger systems.
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| 3. |
- Schuette, Moritz, et al.
(författare)
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Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling 44,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab.
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| 4. |
- Soliveres, Santiago, et al.
(författare)
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Biodiversity at multiple trophic levels is needed for ecosystem multifunctionality
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7617, s. 456-459
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Tidskriftsartikel (refereegranskat)abstract
- Many experiments have shown that loss of biodiversity reduces the capacity of ecosystems to provide the multiple services on which humans depend. However, experiments necessarily simplify the complexity of natural ecosystems and will normally control for other important drivers of ecosystem functioning, such as the environment or land use. In addition, existing studies typically focus on the diversity of single trophic groups, neglecting the fact that biodiversity loss occurs across many taxa and that the functional effects of any trophic group may depend on the abundance and diversity of others. Here we report analysis of the relationships between the species richness and abundance of nine trophic groups, including 4,600 above- and below-ground taxa, and 14 ecosystem services and functions and with their simultaneous provision (or multifunctionality) in 150 grasslands. We show that high species richness in multiple trophic groups (multitrophic richness) had stronger positive effects on ecosystem services than richness in any individual trophic group; this includes plant species richness, the most widely used measure of biodiversity. On average, three trophic groups influenced each ecosystem service, with each trophic group influencing at least one service. Multitrophic richness was particularly beneficial for 'regulating' and 'cultural' services, and for multifunctionality, whereas a change in the total abundance of species or biomass in multiple trophic groups (the multitrophic abundance) positively affected supporting services. Multitrophic richness and abundance drove ecosystem functioning as strongly as abiotic conditions and land-use intensity, extending previous experimental results to real-world ecosystems. Primary producers, herbivorous insects and microbial decomposers seem to be particularly important drivers of ecosystem functioning, as shown by the strong and frequent positive associations of their richness or abundance with multiple ecosystem services. Our results show that multitrophic richness and abundance support ecosystem functioning, and demonstrate that a focus on single groups has led to researchers to greatly underestimate the functional importance of biodiversity.
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| 5. |
- Soliveres, Santiago, et al.
(författare)
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Locally rare species influence grassland ecosystem multifunctionality
- 2016
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Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 371:1694
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Tidskriftsartikel (refereegranskat)abstract
- Species diversity promotes the delivery of multiple ecosystem functions (multifunctionality). However, the relative functional importance of rare and common species in driving the biodiversity-multifunctionality relationship remains unknown. We studied the relationship between the diversity of rare and common species (according to their local abundances and across nine different trophic groups), and multifunctionality indices derived from 14 ecosystem functions on 150 grasslands across a land-use intensity (LUI) gradient. The diversity of above-and below-ground rare species had opposite effects, with rare above-ground species being associated with high levels of multifunctionality, probably because their effects on different functions did not trade off against each other. Conversely, common species were only related to average, not high, levels of multifunctionality, and their functional effects declined with LUI. Apart from the community-level effects of diversity, we found significant positive associations between the abundance of individual species and multifunctionality in 6% of the species tested. Species-specific functional effects were best predicted by their response to LUI: species that declined in abundance with land use intensification were those associated with higher levels of multifunctionality. Our results highlight the importance of rare species for ecosystem multifunctionality and help guiding future conservation priorities.
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| 6. |
- Wang, Qiang, et al.
(författare)
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Hardware/Software Co-design of an ATCA-based Computation Platform for Data Acquisition and Triggering
- 2009
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Ingår i: 16th IEEE NPSS Real Time Conference. - 9781424457960 ; , s. 485-489
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Konferensbidrag (refereegranskat)abstract
- An ATCA-based computation platform for data acquisition and trigger(TDAQ) applications has been developed for multiple future projects such its PANDA. HADES, and BESIII. Each Compute Node (CN) appears as one (if the fourteen Field Replaceable Units (FRU) in an ATCA shelf, which in total features a high performance of 1890 Clips inter-FPGA on-board channels, 1456 Gbps inter-board backplane connections, 728 Gbps full-duplex optical links, 70 Gbps Ethernet. 140 GBytes DDR2 SDRAM. and all computing resources of 70 Xilinx Virtex-4 FX60 FPGAs. Corresponding to (the system architecture, a hardware/software co-design approach is proposed to ease and accelerate the development for different experiments. In the uniform system design. application-specific computation is to be implemented as customized hardware co-processors, while the embedded PowerPC processor takes charge of flexible slow controls and transmission protocol processing.
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| 7. |
- Alves, Guido, et al.
(författare)
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Cerebrospinal fluid amyloid-β and phenotypic heterogeneity in de novo Parkinson's disease.
- 2013
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 84:5, s. 537-43
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Tidskriftsartikel (refereegranskat)abstract
- In Parkinson's disease (PD), the motor presentation characterised by postural instability/gait difficulties (PIGD) heralds accelerated motor, functional and cognitive decline, as compared with the more benign tremor-dominant (TD) variant. This makes the PIGD complex an attractive target for the discovery of prognostic biomarkers in PD.
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| 8. |
- Alves, Guido, et al.
(författare)
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CSF Aβ42 predicts early-onset dementia in Parkinson disease.
- 2014
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Ingår i: Neurology. - 1526-632X. ; 82:20, s. 1784-90
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Tidskriftsartikel (refereegranskat)abstract
- To test in vivo the proposal from clinicopathologic studies that β-amyloid (Aβ) pathology shortens the time to dementia in Parkinson disease (PD), and to explore the utility of CSF Aβ and related measures as early prognostic biomarkers of dementia in an incident PD cohort.
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| 9. |
- Azhar, Najia, et al.
(författare)
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Laparoscopic lavage for Hinchey III perforated diverticulitis : factors for treatment failure in two randomized clinical trials
- 2023
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Ingår i: The British journal of surgery. - 1365-2168. ; 110:7, s. 846-851
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Scandinavian Diverticulitis (SCANDIV) trial and the LOLA arm of the LADIES trial randomized patients with Hinchey III perforated diverticulitis to laparoscopic peritoneal lavage or sigmoid resection. The aim of this analysis was to identify risk factors for treatment failure in patients with Hinchey III perforated diverticulitis.METHODS: This was a post hoc analysis of the SCANDIV trial and LOLA arm. Treatment failure was defined as morbidity requiring general anaesthesia (Clavien-Dindo grade IIIb or higher) within 90 days. Age, sex, BMI, ASA fitness grade, smoking status, previous episodes of diverticulitis, previous abdominal surgery, time to surgery, and surgical competence were all tested in univariable and multivariable logistic regression analyses using an interaction variable.RESULTS: The pooled analysis included 222 patients randomized to laparoscopic lavage and primary resection (116 and 106 patients respectively). Univariable analysis found ASA grade to be associated with advanced morbidity in both groups, and the following factors in the laparoscopic lavage group: smoking, corticosteroid use, and BMI. Significant factors for laparoscopic lavage morbidity in multivariable analysis were smoking (OR 7.05, 95 per cent c.i. 2.07 to 23.98; P = 0.002) and corticosteroid use (OR 6.02, 1.54 to 23.51; P = 0.010).CONCLUSION: Active smoking status and corticosteroid use were risk factors for laparoscopic lavage treatment failure (advanced morbidity) in patients with perforated diverticulitis.
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| 10. |
- Biscarat, Catherine, et al.
(författare)
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New developments in cost modeling for the LHC computing
- 2020
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Ingår i: EPJ Web of Conferences. - : EDP Sciences. - 2100-014X. ; 245, s. 03014-03014
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Tidskriftsartikel (refereegranskat)abstract
- The increase in the scale of LHC computing during Run 3 and Run 4 (HL-LHC) will certainly require radical changes to the computing models and the data processing of the LHC experiments. The working group established by WLCG and the HEP Software Foundation to investigate all aspects of the cost of computing and how to optimise them has continued producing results and improving our understanding of this process. In particular, experiments have developed more sophisticated ways to calculate their resource needs, we have a much more detailed process to calculate infrastructure costs. This includes studies on the impact of HPC and GPU based resources on meeting the computing demands. We have also developed and perfected tools to quantitatively study the performance of experiments workloads and we are actively collaborating with other activities related to data access, benchmarking and technology cost evolution. In this contribution we expose our recent developments and results and outline the directions of future work.
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| 11. |
- Freitag, Daniel F., et al.
(författare)
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Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- 2015
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Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595. ; 3:4, s. 243-253
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Tidskriftsartikel (refereegranskat)abstract
- Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND.
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| 12. |
- Førland, Marthe Gurine, et al.
(författare)
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Evolution of cerebrospinal fluid total α-synuclein in Parkinson's disease.
- 2018
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Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; 49, s. 4-8
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) total α-synuclein is considered a potential biomarker for Parkinson's disease (PD), but little is known about the evolution of this marker during the course of the disease. Our objective was to investigate whether CSF total α-synuclein concentrations change over time and are associated with motor and cognitive function in PD.CSF total α-synuclein concentrations were quantified in 56 longitudinally followed PD patients, 27 of whom provided CSF repeatedly 2 and/or 4 years later. Another 18 subjects were included as controls. The samples were analyzed using two independent, validated ELISA methods: our recently developed and validated in-house ELISA and a commercial kit from BioLegend.CSF total α-synuclein levels did not distinguish PD patients from controls, displayed no substantial changes during a period of up to 4 years, and did not predict subsequent motor or cognitive decline. These findings were consistent for both analytical methods.Our findings do not support the clinical utility of total α-synuclein as a single diagnostic or prognostic biomarker in PD.
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| 13. |
- Førland, Marthe Gurine, et al.
(författare)
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Validation of a new assay for α-synuclein detection in cerebrospinal fluid.
- 2017
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Ingår i: Clinical chemistry and laboratory medicine. - : Walter de Gruyter GmbH. - 1437-4331 .- 1434-6621. ; 55:2, s. 254-260
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Tidskriftsartikel (refereegranskat)abstract
- Abnormal α-synuclein aggregation and deposition is the pathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), but is also found in Alzheimer disease (AD). Therefore, there is a gaining interest in α-synuclein in cerebrospinal fluid (CSF) as potential biomarker for these neurodegenerative diseases. To broaden the available choices of α-synuclein measurement in CSF, we developed and validated a new assay for detecting total α-synuclein.
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| 14. |
- Grooten, Liset, et al.
(författare)
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A scaling-up strategy supporting the expansion of integrated care : a study protocol
- 2019
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Ingår i: Journal of Integrated Care. - : Emerald Group Publishing Limited. - 1476-9018. ; 27:3, s. 215-231
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo ensure that more people will benefit from integrated care initiatives, scaling-up of successful initiatives is the way forward. However, new challenges present themselves as knowledge on how to achieve successful large-scale implementation is scarce. The EU-funded project SCIROCCO uses a step-based scaling-up strategy to explore what to scale-up, and how to scale-up integrated care initiatives by matching the complementary strengths and weaknesses of five European regions involved in integrated care. The purpose of this paper is to describe a multi-method evaluation protocol designed to understand what factors influence the implementation of the SCIROCCO strategy to support the scaling-up of integrated care.Design/methodology/approachThe first part of the protocol focuses on the assessment of the implementation fidelity of the SCIROCCO step-based strategy. The objective is to gain insight in whether the step-based strategy is implemented as it was designed to explore what works and does not work when implementing the scaling-up strategy. The second part concerns a realist evaluation to examine what it is about the SCIROCCO’s strategy that works for whom, why, how and in which circumstances when scaling-up integrated care.FindingsThe intended study will provide valuable information on the implementation of the scaling-up strategy which will help to explain for what specific reasons the implementation succeeds and will facilitate further improvement of project outcomes.Originality/valueThe expected insights could be useful to guide the development, implementation and evaluation of future scaling-up strategies to advance the change towards more sustainable health and care systems.
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| 15. |
- Hagger, Martin S., et al.
(författare)
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A Multilab Preregistered Replication of the Ego-Depletion Effect
- 2016
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Ingår i: Perspectives on Psychological Science. - : Sage Publications. - 1745-6916 .- 1745-6924. ; 11:4, s. 546-573
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Tidskriftsartikel (refereegranskat)abstract
- Good self-control has been linked to adaptive outcomes such as better health, cohesive personal relationships, success in the workplace and at school, and less susceptibility to crime and addictions. In contrast, self-control failure is linked to maladaptive outcomes. Understanding the mechanisms by which self-control predicts behavior may assist in promoting better regulation and outcomes. A popular approach to understanding self-control is the strength or resource depletion model. Self-control is conceptualized as a limited resource that becomes depleted after a period of exertion resulting in self-control failure. The model has typically been tested using a sequential-task experimental paradigm, in which people completing an initial self-control task have reduced self-control capacity and poorer performance on a subsequent task, a state known as ego depletion. Although a meta-analysis of ego-depletion experiments found a medium-sized effect, subsequent meta-analyses have questioned the size and existence of the effect and identified instances of possible bias. The analyses served as a catalyst for the current Registered Replication Report of the ego-depletion effect. Multiple laboratories (k = 23, total N = 2,141) conducted replications of a standardized ego-depletion protocol based on a sequential-task paradigm by Sripada et al. Meta-analysis of the studies revealed that the size of the ego-depletion effect was small with 95% confidence intervals (CIs) that encompassed zero (d = 0.04, 95% CI [-0.07, 0.15]. We discuss implications of the findings for the ego-depletion effect and the resource depletion model of self-control.
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| 16. |
- Ikram, M. Arfan, et al.
(författare)
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Common variants at 6q22 and 17q21 are associated with intracranial volume
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 539-544
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Tidskriftsartikel (refereegranskat)abstract
- During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
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| 17. |
- Karyotaki, Eirini, et al.
(författare)
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Do guided internet-based interventions result in clinically relevant changes for patients with depression? : An individual participant data meta-analysis
- 2018
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Ingår i: Clinical Psychology Review. - : Elsevier. - 0272-7358 .- 1873-7811. ; 63, s. 80-92
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Forskningsöversikt (refereegranskat)abstract
- Little is known about clinically relevant changes in guided Internet-based interventions for depression. Moreover, methodological and power limitations preclude the identification of patients' groups that may benefit more from these interventions. This study aimed to investigate response rates, remission rates, and their moderators in randomized controlled trials (RCTs) comparing the effect of guided Internet-based interventions for adult depression to control groups using an individual patient data meta-analysis approach. Literature searches in PubMed, Embase, PsycINFO and Cochrane Library resulted in 13,384 abstracts from database inception to January 1, 2016. Twenty-four RCTs (4889 participants) comparing a guided Internet-based intervention with a control group contributed data to the analysis. Missing data were multiply imputed. To examine treatment outcome on response and remission, mixed-effects models with participants nested within studies were used. Response and remission rates were calculated using the Reliable Change Index. The intervention group obtained significantly higher response rates (OR = 2.49, 95% CI 2.17-2.85) and remission rates compared to controls (OR = 2.41, 95% CI 2.07-2.79). The moderator analysis indicated that older participants (OR = 1.01) and native-born participants (1.66) were more likely to respond to treatment compared to younger participants and ethnic minorities respectively. Age (OR = 1.01) and ethnicity (1.73) also moderated the effects of treatment on remission.Moreover, adults with more severe depressive symptoms at baseline were more likely to remit after receiving intemet-based treatment (OR = 1.19). Guided Internet-based interventions lead to substantial positive treatment effects on treatment response and remission at post-treatment. Thus, such interventions may complement existing services for depression and potentially reduce the gap between the need and provision of evidence-based treatments.
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| 18. |
- Koens, Lisette H, et al.
(författare)
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Eye movement disorders in inborn errors of metabolism : A quantitative analysis of 37 patients
- 2022
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Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 45:5, s. 981-995
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Tidskriftsartikel (refereegranskat)abstract
- Inborn errors of metabolism are genetic disorders that need to be recognized as early as possible because treatment may be available. In late-onset forms, core symptoms are movement disorders, psychiatric symptoms, and cognitive impairment. Eye movement disorders are considered to be frequent too, although specific knowledge is lacking. We describe and analyze eye movements in patients with an inborn error of metabolism, and see whether they can serve as an additional clue in the diagnosis of particularly late-onset inborn errors of metabolism. Demographics, disease characteristics, and treatment data were collected. All patients underwent a standardized videotaped neurological examination and a video-oculography. Videos are included. We included 37 patients with 15 different inborn errors of metabolism, including 18 patients with a late-onset form. With the exception of vertical supranuclear gaze palsy in Niemann-Pick type C and external ophthalmolplegia in Kearns-Sayre syndrome, no relation was found between the type of eye movement disorder and the underlying metabolic disorder. Movement disorders were present in 29 patients (78%), psychiatric symptoms in 14 (38%), and cognitive deficits in 26 patients (70%). In 87% of the patients with late-onset disease, eye movement disorders were combined with one or more of these core symptoms. To conclude, eye movement disorders are present in different types of inborn errors of metabolism, but are often not specific to the underlying disorder. However, the combination of eye movement disorders with movement disorders, psychiatric symptoms, or cognitive deficits can serve as a diagnostic clue for an underlying late-onset inborn error of metabolism.
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| 19. |
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| 20. |
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| 21. |
- Liu, Ming, et al.
(författare)
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A High-End Reconfigurable Computation Platform for Nuclear and Particle Physics Experiments
- 2011
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Ingår i: Computing in science & engineering (Print). - 1521-9615 .- 1558-366X. ; 13:2, s. 52-63
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Tidskriftsartikel (refereegranskat)abstract
- A high-performance computation platform based on field-programmable gate arrays targets nuclear and particle physics experiment applications. The system can be constructed or scaled into a supercomputer-equivalent size for detector data processing by inserting compute nodes into advanced telecommunications computing architecture (ATCA) crates. Among the case study results are that one ATCA crate can provide a computation capability equivalent to hundreds of commodity PCs for Hades online particle track reconstruction and Cherenkov ring recognition.
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| 22. |
- Lübke, Johannes, et al.
(författare)
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Prognostic Impact of Organomegaly in Mastocytosis : An Analysis of the European Competence Network on Mastocytosis
- 2023
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 2213-2198 .- 2213-2201. ; 11:2, s. 581-590
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Organomegaly, including splenomegaly, hepatomegaly, and/or lymphadenopathy, are important diagnostic and prognostic features in patients with cutaneous mastocytosis (CM) or systemic mastocytosis (SM).OBJECTIVES: To investigate the prevalence and prognostic impact of 1 or more organomegalies on clinical course and survival in patients with CM/SM.METHODS: Therefore, 3155 patients with CM (n = 1002 [32%]) or SM (n = 2153 [68%]) enrolled within the registry of the European Competence Network on Mastocytosis were analyzed. RESULTS: Overall survival (OS) was adversely affected by the number of organomegalies (OS: #0 vs #1 hazard ratio [HR], 4.9; 95% CI, 3.4-7.1, P < .001; #1 vs #2 HR, 2.1, 95% CI, 1.4-3.1, P < .001; #2 vs #3 HR, 1.7, 95% CI, 1.2-2.5, P = .004). Lymphadenopathy was frequently detected in patients with smoldering SM (SSM, 18 of 60 [30%]) or advanced SM (AdvSM, 137 of 344 [40%]). Its presence confered an inferior outcome in patients with AdvSM compared with patients with AdvSM without lymphadenopathy (median OS, 3.8 vs 2.6 years; HR, 1.6; 95% CI, 1.2-2.2; P = .003). OS was not different between patients having organomegaly with either ISM or SSM (median, 25.5 years vs not reached; P = .435). At time of disease progression, a new occurrence of any organomegaly was observed in 17 of 40 (43%) patients with ISM, 4 of 10 (40%) patients with SSM, and 33 of 86 (38%) patients with AdvSM, respectively.CONCLUSIONS: Organomegalies including lymphadenopathy are often found in SSM and AdvSM. ISM with organomegaly has a similar course and prognosis compared with SSM. The number of organomegalies is adversely associated with OS. A new occurrence of organomegaly in all variants of SM may indicate disease progression.
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| 23. |
- Lübke, Johannes, et al.
(författare)
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Serum chemistry profiling and prognostication in systemic mastocytosis : a registry-based study of the ECNM and GREM
- 2024
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 8:11, s. 2890-2900
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Tidskriftsartikel (refereegranskat)abstract
- Certain laboratory abnormalities correlate with subvariants of systemic mastocytosis (SM) and are often prognostically relevant. To assess the diagnostic and prognostic value of individual serum chemistry parameters in SM, 2607 patients enrolled within the European Competence Network on Mastocytosis and 575 patients enrolled within the German Registry on Eosinophils and Mast Cells were analyzed. For screening and diagnosis of SM, tryptase was identified as the most speci fic serum parameter. For differentiation between indolent and advanced SM (AdvSM), the following serum parameters were most relevant: tryptase, alkaline phosphatase, beta 2-microglobulin, lactate dehydrogenase (LDH), albumin, vitamin B12, and C-reactive protein (P < .001). With regard to subvariants of AdvSM, an elevated LDH of ≥ 260 U/L was associated with multilineage expansion (leukocytosis, r = 0.37, P < .001; monocytosis, r = 0.26, P < .001) and the presence of an associated myeloid neoplasm (P < .001), whereas tryptase levels were highest in mast cell leukemia (MCL) vs non-MCL (308 μg/L vs 146 μg/L, P = .003). Based on multivariable analysis, the hazard-risk weighted assignment of 1 point to LDH (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.1-4.0; P = .018) and 1.5 points each to β2-microglobulin (HR, 2.7; 95% CI, 1.4-5.4; P = .004) and albumin (HR, 3.3; 95% CI, 1.7-6.5; P = .001) delineated a highly predictive 3-tier risk classification system (0 points, 8.1 years vs 1 point, 2.5 years; ≥1.5 points, 1.7 years; P < .001). Moreover, serum chemistry parameters enabled further stratification of patients classified as having an International Prognostic Scoring System for Mastocytosis-AdvSM1/2 risk score (P = .027). In conclusion, serum chemistry pro filing is a crucial tool in the clinical practice supporting diagnosis and prognostication of SM and its subvariants.
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| 24. |
- Lyon, Helen N., et al.
(författare)
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The association of a SNP upstream of INSIG2 with body mass index is reproduced in several but not all cohorts
- 2007
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- A SNP upstream of the INSIG2 gene, rs7566605, was recently found to be associated with obesity as measured by body mass index (BMI) by Herbert and colleagues. The association between increased BMI and homozygosity for the minor allele was first observed in data from a genome-wide association scan of 86,604 SNPs in 923 related individuals from the Framingham Heart Study offspring cohort. The association was reproduced in four additional cohorts, but was not seen in a fifth cohort. To further assess the general reproducibility of this association, we genotyped rs7566605 in nine large cohorts from eight populations across multiple ethnicities (total n = 16,969). We tested this variant for association with BMI in each sample under a recessive model using family-based, population-based, and case-control designs. We observed a significant (p < 0.05) association in five cohorts but saw no association in three other cohorts. There was variability in the strength of association evidence across examination cycles in longitudinal data from unrelated individuals in the Framingham Heart Study Offspring cohort. A combined analysis revealed significant independent validation of this association in both unrelated (p = 0.046) and family-based (p = 0.004) samples. The estimated risk conferred by this allele is small, and could easily be masked by small sample size, population stratification, or other confounders. These validation studies suggest that the original association is less likely to be spurious, but the failure to observe an association in every data set suggests that the effect of SNP rs7566605 on BMI may be heterogeneous across population samples.
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| 25. |
- Patil, Ketan S., et al.
(författare)
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Combinatory microRNA serum signatures as classifiers of Parkinson's disease
- 2019
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 64, s. 202-210
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: As current clinical diagnostic protocols for Parkinson's disease (PD) may be prone to inaccuracies there is a need to identify and validate molecular biomarkers, such as circulating microRNAs, which will complement current practices and increase diagnostic accuracy. This study identifies, verifies and validates combinatory serum microRNA signatures as diagnostic classifiers of PD across different patient cohorts. Methods: 370 PD (drug naive) and control serum samples from the Norwegian ParkWest study were used for identification and verification of differential microRNA levels in PD which were validated in a blind study using 64 NY Parkinsonism in UMea (NYPUM) study serum samples and tested for specificity in 48 Dementia Study of Western Norway (DemWest) study Alzheimer's disease (AD) serum samples using miRNA-microarrays, and quantitative (q) RT-PCR. Proteomic approaches identified potential molecular targets for these microRNAs. Results: Using Affymetrix GeneChip (R) miRNA 4.0 arrays and qRT-PCR we comprehensively analyzed serum microRNA levels and found that the microRNA (PARKmiR)-combinations, hsa-miR-335-5p/hsa-miR-3613-3p (95% CI, 0.87-0.94), hsa-miR-335-5p/hsa-miR-6865-3p (95% CI, 0.87-0.93), and miR-335-5p/miR-3613-3p/miR-6865-3p (95% CI, 0.87-0.94) show a high degree of discriminatory accuracy (AUC 0.9-1.0). The PARKmiR signatures were validated in an independent PD cohort (AUC <= 0.71) and analysis in AD serum samples showed PARKmiR signature specificity to PD. Proteomic analyses showed that the PAFtKmiRs regulate key PD-associated proteins, including alpha-synuclein and Leucine Rich Repeat Kinase 2. Conclusions: Our study has identified and validated unique miRNA serum signatures that represent PD classifiers, which may complement and increase the accuracy of current diagnostic protocols.
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| 26. |
- Pisek, Jan, et al.
(författare)
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Retrieval and validation of forest background reflectivity from daily Moderate Resolution Imaging Spectroradiometer (MODIS) bidirectional reflectance distribution function (BRDF) data across European forests
- 2021
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 18:2, s. 621-635
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Tidskriftsartikel (refereegranskat)abstract
- Information about forest background reflectance is needed for accurate biophysical parameter retrieval from forest canopies (overstory) with remote sensing. Separating under- and overstory signals would enable more accurate modeling of forest carbon and energy fluxes. We retrieved values of the normalized difference vegetation index (NDVI) of the forest understory with the multi-angular Moderate Resolution Imaging Spectroradiometer (MODIS) bidirectional reflectance distribution function (BRDF)/albedo data (gridded 500 m daily Collection 6 product), using a method originally developed for boreal forests. The forest floor background reflectance estimates from the MODIS data were compared with in situ understory reflectance measurements carried out at an extensive set of forest ecosystem experimental sites across Europe. The reflectance estimates from MODIS data were, hence, tested across diverse forest conditions and phenological phases during the growing season to examine their applicability for ecosystems other than boreal forests. Here we report that the method can deliver good retrievals, especially over different forest types with open canopies (low foliage cover). The performance of the method was found to be limited over forests with closed canopies (high foliage cover), where the signal from understory becomes too attenuated. The spatial heterogeneity of individual field sites and the limitations and documented quality of the MODIS BRDF product are shown to be important for the correct assessment and validation of the retrievals obtained with remote sensing.
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| 27. |
- Sumaila, U. Rashid, et al.
(författare)
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WTO must ban harmful fisheries subsidies
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 28. |
- Szwedo, Aleksandra A., et al.
(författare)
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Association of SNCA Parkinson's Disease Risk Polymorphisms With Disease Progression in Newly Diagnosed Patients
- 2021
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Ingår i: Frontiers in Neurology. - : Frontiers. - 1664-2295. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the impact of SNCA polymorphisms originally identified as risk factors for Parkinson's disease (PD) on the clinical presentation and progression of the disease in a large cohort of population-based patients with incident PD. Methods: Four hundred thirty-three patients and 417 controls from three longitudinal cohorts were included in the study. Disease progression was recorded annually for up to 9 years using the Unified Parkinson's Disease Rating Scale (UPDRS) or Mini-Mental State Examination. Genotypes for five variants within the SNCA locus (rs2870004, rs356182, rs5019538, rs356219, and rs763443) were determined. We studied the association between each variant and disease progression using linear mixed-effects regression models. Results: The clinical profile of the patients with PD at the point of diagnosis was highly uniform between genotype groups. The rs356219-GG genotype was associated with a higher UPDRS II score than A-allele carriers (β = 1.52; 95% confidence interval 0.10–2.95; p = 0.036), but no differences were observed in the rate of progression of the UPDRS II scores. rs356219-GG was also associated with a faster annual change in Mini-Mental State Examination score compared with A-carriers (β = 0.03; 95% confidence interval 0.00–0.06; p = 0.043). Conclusions: We show that the known PD-risk variant rs356219 has a minor effect on modifying disease progression, whereas no differences were associated with rs2870004, rs356182, rs5019538, and rs763443. These findings suggest that SNCA variants associated with PD risk may not be major driving factors to the clinical heterogeneity observed for PD.
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| 29. |
- Taal, H. Rob, et al.
(författare)
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Common variants at 12q15 and 12q24 are associated with infant head circumference
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
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| 30. |
- Teslovich, Tanya M., et al.
(författare)
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Biological, clinical and population relevance of 95 loci for blood lipids
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7307, s. 707-713
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Tidskriftsartikel (refereegranskat)abstract
- Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
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| 31. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 32. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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