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| 3. |
- Middeldorp, Christel M., et al.
(author)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Journal article (peer-reviewed)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 4. |
- Costa, M, et al.
(author)
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Results from an ATM-based event builder demonstrator
- 1996
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In: IEEE TRANSACTIONS ON NUCLEAR SCIENCE. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 0018-9499. ; 43:3, s. 1814-1820
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Journal article (other academic/artistic)abstract
- ATM switching fabrics are good candidates to implement high performance parallel event builders for the future data acquisition systems in particle physics experiments. We are studying their feasibility through simulations and implementation of event buil
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| 6. |
- Ambros, I. M., et al.
(author)
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Age Dependency of the Prognostic Impact of Tumor Genomics in Localized Resectable MYCN-Nonamplified Neuroblastomas. Report From the SIOPEN Biology Group on the LNESG Trials and a COG Validation Group
- 2020
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In: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 38:31
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Journal article (peer-reviewed)abstract
- PURPOSEFor localized, resectable neuroblastoma without MYCN amplification, surgery only is recommended even if incomplete. However, it is not known whether the genomic background of these tumors may influence outcome.PATIENTS AND METHODSDiagnostic samples were obtained from 317 tumors, International Neuroblastoma Staging System stages 1/2A/2B, from 3 cohorts: Localized Neuroblastoma European Study Group I/II and Children's Oncology Group. Genomic data were analyzed using multi- and pangenomic techniques and fluorescence in-situ hybridization in 2 age groups (cutoff age, 18 months) and were quality controlled by the International Society of Pediatric Oncology European Neuroblastoma (SIOPEN) Biology Group.RESULTSPatients with stage 1 tumors had an excellent outcome (5-year event-free survival [EFS] standard deviation [SD], 95% +/- 2%; 5-year overall survival [OS], 99% +/- 1%). In contrast, patients with stage 2 tumors had a reduced EFS in both age groups (5-year EFS +/- SD, 84% +/- 3% in patients < 18 months of age and 75% 7% in patients >= 18 months of age). However, OS was significantly decreased only in the latter group (5-year OS +/- SD in < 18months and 18months, 96% +/- 2% and 81% +/- 7%, respectively; P = .001). In < 18months, relapses occurred independent of segmental chromosome aberrations (SCAs); only 1p loss decreased EFS (5-year EFS SD in patients 1p loss and no 1p loss, 62% +/- 13% and 87% +/- 3%, respectively; P = .019) but not OS (5-year OS +/- SD, 92% +/- 8% and 97% +/- 2%, respectively). In patients >= 18 months, only SCAs led to relapse and death, with 11q loss as the strongest marker (11q loss and no 11q loss: 5-year EFS +/- SD, 48% +/- 16% and 85% +/- 7%, P = .033; 5-year OS +/- SD, 46% +/- 22% and 92% +/- 6%, P = .038).CONCLUSIONGenomic aberrations of resectable non-MYCN-amplified stage 2 neuroblastomas have a distinct age-dependent prognostic impact. Chromosome 1p loss is a risk factor for relapse but not for diminished OS in patients < 18 months, SCAs (especially 11q loss) are risk factors for reduced EFS and OS in those > 18months. In older patients with SCA, a randomized trial of postoperative chemotherapy compared with observation alone may be indicated.
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| 7. |
- Hangen, E, et al.
(author)
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A brain-specific isoform of mitochondrial apoptosis-inducing factor: AIF2.
- 2010
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In: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 17:7, s. 1155-66
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Journal article (peer-reviewed)abstract
- Apoptosis-inducing factor (AIF) has important supportive as well as potentially lethal roles in neurons. Under normal physiological conditions, AIF is a vital redox-active mitochondrial enzyme, whereas in pathological situations, it translocates from mitochondria to the nuclei of injured neurons and mediates apoptotic chromatin condensation and cell death. In this study, we reveal the existence of a brain-specific isoform of AIF, AIF2, whose expression increases as neuronal precursor cells differentiate. AIF2 arises from the utilization of the alternative exon 2b, yet uses the same remaining 15 exons as the ubiquitous AIF1 isoform. AIF1 and AIF2 are similarly imported to mitochondria in which they anchor to the inner membrane facing the intermembrane space. However, the mitochondrial inner membrane sorting signal encoded in the exon 2b of AIF2 is more hydrophobic than that of AIF1, indicating a stronger membrane anchorage of AIF2 than AIF1. AIF2 is more difficult to be desorbed from mitochondria than AIF1 on exposure to non-ionic detergents or basic pH. Furthermore, AIF2 dimerizes with AIF1, thereby preventing its release from mitochondria. Conversely, it is conceivable that a neuron-specific AIF isoform, AIF2, may have been 'designed' to be retained in mitochondria and to minimize its potential neurotoxic activity.Cell Death and Differentiation advance online publication, 29 January 2010; doi:10.1038/cdd.2009.211.
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| 11. |
- Defferrari, R., et al.
(author)
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Influence of segmental chromosome abnormalities on survival in children over the age of 12 months with unresectable localised peripheral neuroblastic tumours without MYCN amplification
- 2015
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 112:2, s. 290-295
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Journal article (peer-reviewed)abstract
- Background: The prognostic impact of segmental chromosome alterations (SCAs) in children older than 1 year, diagnosed with localised unresectable neuroblastoma (NB) without MYCN amplification enrolled in the European Unresectable Neuroblastoma (EUNB) protocol is still to be clarified, while, for other group of patients, the presence of SCAs is associated with poor prognosis. Methods: To understand the role of SCAs we performed multilocus/pangenomic analysis of 98 tumour samples from patients enrolled in the EUNB protocol. Results: Age at diagnosis was categorised into two groups using 18 months as the age cutoff. Significant difference in the presence of SCAs was seen in tumours of patients between 12 and 18 months and over 18 months of age at diagnosis, respectively (P = 0.04). A significant correlation (P = 0.03) was observed between number of SCAs per tumour and age. Event-free (EFS) and overall survival (OS) were calculated in both age groups, according to both the presence and number of SCAs. In older patients, a poorer survival was associated with the presence of SCAs (EFS = 46% vs 75%, P = 0.023; OS = 66.8% vs 100%, P = 0.003). Moreover, OS of older patients inversely correlated with number of SCAs (P = 0.002). Finally, SCAs provided additional prognostic information beyond histoprognosis, as their presence was associated with poorer OS in patients over 18 months with unfavourable International Neuroblastoma Pathology Classification (INPC) histopathology (P = 0.018). Conclusions: The presence of SCAs is a negative prognostic marker that impairs outcome of patients over the age of 18 months with localised unresectable NB without MYCN amplification, especially when more than one SCA is present. Moreover, in older patients with unfavourable INPC tumour histoprognosis, the presence of SCAs significantly affects OS.
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| 14. |
- Serenelli, Aldo, et al.
(author)
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Weighing stars from birth to death : mass determination methods across the HRD
- 2021
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In: Astronomy and Astrophysics Review. - : Springer Science and Business Media LLC. - 0935-4956 .- 1432-0754. ; 29:1
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Research review (peer-reviewed)abstract
- The mass of a star is the most fundamental parameter for its structure, evolution, and final fate. It is particularly important for any kind of stellar archaeology and characterization of exoplanets. There exist a variety of methods in astronomy to estimate or determine it. In this review we present a significant number of such methods, beginning with the most direct and model-independent approach using detached eclipsing binaries. We then move to more indirect and model-dependent methods, such as the quite commonly used isochrone or stellar track fitting. The arrival of quantitative asteroseismology has opened a completely new approach to determine stellar masses and to complement and improve the accuracy of other methods. We include methods for different evolutionary stages, from the pre-main sequence to evolved (super)giants and final remnants. For all methods uncertainties and restrictions will be discussed. We provide lists of altogether more than 200 benchmark stars with relative mass accuracies between [0.3 , 2] % for the covered mass range of M∈[0.1,16]M⊙, 75 % of which are stars burning hydrogen in their core and the other 25 % covering all other evolved stages. We close with a recommendation how to combine various methods to arrive at a “mass-ladder” for stars.
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| 15. |
- Seth-Smith, Helena M. B., et al.
(author)
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Ongoing evolution of Chlamydia trachomatis lymphogranuloma venereum : exploring the genomic diversity of circulating strains
- 2021
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In: Microbial Genomics. - : Microbiology Society. - 2057-5858. ; 7:6
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Journal article (peer-reviewed)abstract
- Lymphogranuloma venereum (LGV), the invasive infection of the sexually transmissible infection (STI) Chlamydia trachomatis, is caused by strains from the LGV biovar, most commonly represented by ompA- genotypes L2b and L2. We investigated the diversity in LGV samples across an international collection over seven years using typing and genome sequencing. LGV- positive samples (n=321) from eight countries collected between 2011 and 2017 (Spain n=97, Netherlands n=67, Switzerland n=64, Australia n=53, Sweden n=37, Hungary n=31, Czechia n=30, Slovenia n=10) were genotyped for pmpH and ompA variants. All were found to contain the 9 bp insertion in the pmpH gene, previously associated with ompA- genotype L2b. However, analysis of the ompA gene shows ompA- genotype L2b (n=83), ompA- genotype L2 (n=180) and several variants of these (n=52; 12 variant types), as well as other/mixed ompA-genotypes (n=6). To elucidate the genomic diversity, whole genome sequencing (WGS) was performed from selected samples using SureSelect target enrichment, resulting in 42 genomes, covering a diversity of ompA- genotypes and representing most of the countries sampled. A phylogeny of these data clearly shows that these ompA- genotypes derive from an ompA- genotype L2b ancestor, carrying up to eight SNPs per isolate. SNPs within ompA are overrep-resented among genomic changes in these samples, each of which results in an amino acid change in the variable domains of OmpA (major outer membrane protein, MOMP). A reversion to ompA- genotype L2 with the L2b genomic backbone is commonly seen. The wide diversity of ompA- genotypes found in these recent LGV samples indicates that this gene is under immunological selection. Our results suggest that the ompA- genotype L2b genomic backbone is the dominant strain circulating and evolving particularly in men who have sex with men (MSM) populations.
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| 16. |
- Ambros, Inge M, et al.
(author)
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A multilocus technique for risk evaluation of patients with neuroblastoma.
- 2011
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In: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 17:4, s. 792-804
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Journal article (peer-reviewed)abstract
- Precise and comprehensive analysis of neuroblastoma genetics is essential for accurate risk evaluation and only pangenomic/multilocus approaches fulfill the present-day requirements. We present the establishment and validation of the PCR-based multiplex ligation-dependent probe amplification (MLPA) technique for neuroblastoma.
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| 21. |
- Flamant, C, et al.
(author)
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[Top five neonatal articles 2015]
- 2016
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In: Archives de pediatrie : organe officiel de la Societe francaise de pediatrie. - : Elsevier BV. - 1769-664X. ; 23:9, s. 996-1001
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Journal article (peer-reviewed)
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| 22. |
- Gustafsson, RKL, et al.
(author)
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Direct infection of primary endothelial cells with human cytomegalovirus prevents angiogenesis and migration
- 2015
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In: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 96:12, s. 3598-3612
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Journal article (peer-reviewed)abstract
- Human cytomegalovirus (hCMV) is a beta herpesvirus that establishes lifelong infection. Although the virus does not usually cause overt clinical symptoms in immunocompetent individuals it can have deleterious effects in immunocompromised patients, such as those on post-transplant medication or with HIV infection. hCMV is the most common congenital infection and can lead to serious fetal sequelae. Endothelial cells (ECs) are natural hosts for hCMVin vivo, therefore, investigations of how this cell type is modulated by infection are key to understanding hCMV pathogenesis. Previous studies have examined the effect of secretomes from hCMV-infected cells on EC angiogenesis, whereas the effect of direct infection on this process has not been so well investigated. Here, we show that placental ECs are viral targets during congenital infection and that vessels in infected tissue appear morphologically abnormal. We demonstrate that the clinical hCMV strain VR1814 impaired EC tube assembly inin vitroangiogenesis assays and inhibited wound healing ability in scratch assays. Secretomes from infected cultures did not impair angiogenesis of uninfected ECs, suggesting that cell-intrinsic changes, as opposed to secreted factors, were responsible. We observed viral gene transcription dependent downregulation of the expression of angiogenesis-associated genes, including angiopoietin-2, TEK receptor and vascular endothelial growth factor receptors. An alternative clinical hCMV stain, TB40E showed similar effects on EC angiogenesis. Together, our data indicate that direct infection with hCMV can induce an anti-migratory and anti-angiogenic EC phenotype, which could have a detrimental effect on the vasculature development in infected tissues.
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| 23. |
- Juma, Benard, et al.
(author)
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Flooding in the urban fringes : Analysis of flood inundation and hazard levels within the informal settlement of Kibera in Nairobi, Kenya
- 2023
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In: Physics and Chemistry of the Earth. - : Elsevier BV. - 1474-7065 .- 1873-5193. ; 132, s. 103499-
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Journal article (peer-reviewed)abstract
- Overlapping conditions of rapid urbanisation and climate change across developing countries are threatening the capacity of cities to manage climate risks, especially in the flood-exposed low-income peripheral areas. Limited studies have applied hydrodynamic flood models in ascertaining flooding conditions, supportive of risk-informed decisions in such urban fringes. Against this backdrop, we assessed plausible flooding and hazard conditions in the low-lying villages of Lindi and Silanga in Kibera informal settlement. The coupled one-dimensional and two-dimensional hydrodynamic model, customised from the Hydrological Engineering Centre's River Analysis System (HEC-RAS) was parameterised for flood simulation under different hydrological regimes and scenarios associated with flooding in Kibera. Volumetric flow estimates and a computed energy slope were used to define the upstream and downstream modelling boundary conditions respectively. Trial-and-error adjustment of the flow resistance coefficients from land-use features was applied in model calibration, and the results compared to the surveyed flood of 23rd April 2019. Results show that proximal areas to the Ngong River and Nairobi dam face high flood risks. A flood volume of 11.7×105m3 from a 2.5h, 50 mm rainfall could potentially inundate about 2.0% and 8.3% of areas in Lindi and Silanga respectively, while a volume of 48.9×105m3 from a 100-year storm of 172 mm could inundate about 10.6% of Lindi and 29.1% of Silanga. Upstream steeply sloping topographies of the villages increase flood velocities and risk of drowning, while the lower reaches at relatively flatter topographies, experience attenuated flow and rapid accumulation of flood waters, hence, higher flood depths. These results can support policy interventions for integrated flood risk management in Kibera, as a way of mainstreaming the underserved urban communities in climate risk management.
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| 24. |
- Juma, Benard, et al.
(author)
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Simulation of flood peak discharges and volumes for flood risk management in the ungauged urban informal settlement of Kibera, Kenya
- 2022
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In: Physics and Chemistry of the Earth. - : Elsevier BV. - 1474-7065 .- 1873-5193. ; 128
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Journal article (peer-reviewed)abstract
- In spite of the increasing extremity and adverse consequences of urban floods under climate change, flood characteristics in most developing countries are still largely unknown due to lack of continuous monitoring. This portentous uncertainty stances high flood risk, especially to a majority low-income urban population inhabiting the flood-prone informal settlements. Physically-based hydrologic models, whose parameters are derivable from catchment features, are often used for hydrological analysis in the ungauged regions. In this study, the Hydro-logic Engineering Centre's-Hydrologic Modelling System (HEC-HMS) was used for rainfall-runoff simulation in the upper Ngong River Basin of Kenya, draining into the Kibera informal settlement, for purposes of estimating flood peak discharges (FPDs) and direct runoff volumes (DRVs), often required for flood risk management. The Soil Conservation Service-Curve Number (SCS-CN), SCS-Unit Hydrograph (SCS-UH) and Muskingum models were used for hydrological simulation from four (4) observed and fifty-four (54) hypothetical extreme rainfalls. The results obtained indicated that a 50 mm rainfall event with a duration of 2.5 h has the potential of producing FPD and DRV of about 90m3s-1 and 1.17 x 106m3 respectively at the Ngong River confluence at Sokomoko in Kibera. On the other hand, the non-intermittent 100-year storm event of about 172 mm in depth, occurring over a period of about 4 h, potentially generated FPD of about 460m3s-1 and DRV of about 4.89 x 106m3, portending calamitous impacts in the basin. These results can offer preliminary information on potential flood character-istics, that can be used as a baseline to support local-level flood risk mitigation measures in the ungauged Ngong River Basin.
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| 25. |
- King, Michael A., et al.
(author)
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A Monte Carlo investigation of artifacts caused by liver uptake in single-photon emission computed tomography perfusion imaging with technetium 99m-labeled agents
- 1996
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In: Journal of Nuclear Cardiology. - 1532-6551. ; 3:1, s. 18-29
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Journal article (peer-reviewed)abstract
- BACKGROUND: Significant hepatobiliary accumulation of technetium 99m-labeled cardiac perfusion agents has been shown to cause alterations in the apparent localization of the agents in the cardiac walls. A Monte Carlo study was conducted to investigate the hypothesis that the cardiac count changes are due to the inconsistencies in the projection data input to reconstruction, and that correction of the causes of these inconsistencies before reconstruction, or including knowledge of the physics underlying them in the reconstruction algorithm, would virtually eliminate these artifacts. METHODS AND RESULTS: The SIMIND Monte Carlo package was used to simulate 64 x 64 pixel projection images at 128 angles of the three-dimensional mathematical cardiac-torso (MCAT) phantom. Simulations were made of (1) a point source in the liver, (2) cardiac activity only, and (3) hepatic activity only. The planar projections and reconstructed point spread functions (PSFs) of the point source in the liver were investigated to study the nature of the inconsistencies introduced into the projections by imaging, and how these affect the distribution of counts in the reconstructed slices. Bull's eye polar maps of the counts at the center of the left ventricular wall of filtered back-projection (FBP) and maximum-likelihood expectation-maximization (MLEM) reconstructions of projections with solely cardiac activity, and with cardiac activity plus hepatic activity scaled to have twice the cardiac concentration, were compared to determine the magnitude and location of apparent changes in cardiac activity when hepatic activity is present. Separate simulations were made to allow the investigation of stationary spatial resolution, distance-dependent spatial resolution, attenuation, and scatter. The point source projections showed significant inconsistencies as a function of projection angle with the largest effect being caused by attenuation. When consistent projections were simulated, no significant impact of hepatic activity on cardiac counts was noted with FBP, or 100 iterations of MLEM. With inconsistent projections, reconstruction of 180 degrees resulted in greater apparent cardiac count losses than did 360 degrees reconstruction for both FBP and MLEM. The incorporation of attenuation correction in MLEM reconstruction reduced the changes in cardiac counts to that seen in simulations in which attenuation was not included, but resulted in increased apparent localization of activity in the posterior wall of the left ventricle when scatter was present in the simulated images. CONCLUSIONS: The apparent alterations in cardiac counts when significant hepatic localization is present is due to the inconsistency of the projections inherent in imaging. Prior correction of these, or accounting for them in the reconstruction algorithm, will virtually eliminate them as causes of artifactual changes in localization. Attenuation correction and scatter correction are both required to overcome the major sources of apparent count changes in the heart associated with hepatic uptake.
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| 26. |
- La Merrill, M. A., et al.
(author)
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Perinatal DDT Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice
- 2016
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In: Environmental Health Perspectives. - 0091-6765. ; 124:11, s. 1722-1727
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Journal article (peer-reviewed)abstract
- BACKGROUND: Dichlorodiphenyltrichloroethane (DDT) was used extensively to control malaria, typhus, body lice, and bubonic plague worldwide, until countries began restricting its use in the 1970s. However, the use of DDT to control vector-borne diseases continues in developing countries. Prenatal DDT exposure is associated with elevated blood pressure in humans. OBJECTIVE: We hypothesized that perinatal DDT exposure causes hypertension in adult mice. METHODS: DDT was administered to C57BL/6J dams from gestational day 11.5 to postnatal day 5. Blood pressure (BP) and myocardial wall thickness were measured in male and female adult offspring. Adult mice were treated with an angiotensin converting enzyme (ACE) inhibitor, captopril, to evaluate sensitivity to amelioration of DDT-associated hypertension by ACE inhibition. We further assessed the influence of DDT exposure on the expression of mRNAs that regulate BP through renal ion transport. RESULTS: Adult mice perinatally exposed to DDT exhibited chronically increased systolic BP, increased myocardial wall thickness, and elevated expression of mRNAs of several renal ion transporters. Captopril completely reversed hypertension in mice perinatally exposed to DDT. CONCLUSIONS: These data demonstrate that perinatal exposure to DDT causes hypertension and cardiac hypertrophy in adult offspring. A key mechanism underpinning this hypertension is an overactivated renin angiotensin system because ACE inhibition reverses the hypertension induced by perinatal DDT exposure.
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| 27. |
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| 28. |
- Pawar, Harvinder, et al.
(author)
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Ghost admixture in eastern gorillas
- 2023
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In: Nature Ecology & Evolution. - : Springer Nature. - 2397-334X. ; 7:9, s. 1503-1514
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Journal article (peer-reviewed)abstract
- Archaic admixture has had a significant impact on human evolution with multiple events across different clades, including from extinct hominins such as Neanderthals and Denisovans into modern humans. Within the great apes archaic admixture has been identified in chimpanzees and bonobos, but the possibility of such events has not been explored in other species. Here, we address this question using high-coverage whole genome sequences from all four extant gorilla subspecies, including six newly sequenced eastern gorillas from previously unsampled geographic regions. Using Approximate Bayesian Computation (ABC) with neural networks to model the demographic history of gorillas, we find a signature of admixture from an archaic 'ghost' lineage into the common ancestor of eastern gorillas, but not western gorillas. We infer that up to 3% of the genome of these individuals is introgressed from an archaic lineage that diverged more than 3 million years ago from the common ancestor of all extant gorillas. This introgression event took place before the split of mountain and eastern lowland gorillas, likely more than 40 thousand years ago, and may have influenced perception of bitter taste in eastern gorillas. When comparing the introgression landscapes of gorillas, humans and bonobos, we find a consistent depletion of introgressed fragments on the X chromosome across these species. However, depletion in protein-coding content is not detectable in eastern gorillas, possibly as a consequence of stronger genetic drift in this species.
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| 29. |
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| 30. |
- Silvestrov, Dmitrii, 1947-, et al.
(author)
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Coupling and Ergodic Theorems for Markov Chains with Damping Component
- 2019
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In: Theory of Probability and Mathematical Statistics. - : American Mathematical Society (AMS). - 0094-9000 .- 1547-7363. ; 101, s. 212-231
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Journal article (peer-reviewed)abstract
- Coupling method is used for geting ergodic theorems for perturbed Markov chains with damping component and rates of convergence in such theorems.
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