160 research outputs found
Invasive Alien Species in Belgian marine waters: an information platform and checklist for science and policy support
Since 2006, the ‘VLIZ Alien Species Consortium’ has collected data and information on species that were introduced by humans in marine and brackish habitats and have established reproducing populations in the study area. The consortium consists of a network of experts in marine and brackish environments in Belgium, representing more than 22 different institutions and supported by a secretariat hosted at Flanders Marine Institute VLIZ. Evidence on invasiveness is reported for 12 of the 73 alien species that are currently included in the checklist for the study area (October 2014). The network brings together scientific information from distributed sources in a central platform. It is a first step to developing an evidence-based approach to inform environmental policy objectives for Belgian marine waters and support effective measures to address invasive alien species in the study area. The information platform and species checklist are presented, approaches for collection and integration of information are described, and opportunities for collaboration between information systems at different governance levels are briefly discussed
Elevated levels of the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in sera of cancer patients.
The concentration of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) was determined in the serum of 90 untreated and 42 treated metastatic cancer patients, including patients with colorectal, breast, ovarian and renal carcinomas, with an enzyme-linked immunosorbent assay (ELISA). Levels higher than the 95th percentile of the concentrations of a control group, i.e. 7.5 pg ml(-1) for bFGF and 500 pg ml(-1) for VEGF, were identified as 'elevated'. One measurement during follow-up was included into the analysis per patient. For 19 treated patients, consecutive serum samples were analysed. Fifty-seven per cent of all untreated patients had elevated serum levels of one or both angiogenic factors. The fraction of patients with elevated serum levels of bFGF and/or VEGF was similar in the different tumour types. Agreement of bFGF levels and VEGF levels, classified in relation to their respective cut-off values, was present in 67% of all patients. Fifty-eight per cent of the patients with progressive disease during treatment compared with 15% of the patients showing response to treatment (chi-squared test P < 0.05) had elevated bFGF and/or VEGF serum levels. When consecutive serum samples were analysed, two-thirds of the patients showing progressive disease had increasing serum levels of the angiogenic factors compared with less than one-tenth of the patients showing response (chi-squared test P < 0.05). The lack of association between the serum bFGF and VEGF levels and the tumour type may suggest an aspecific host reaction responsible for solid tumour-related angiogenesis. The main determinants of the serum bFGF and VEGF concentration are the progression kinetics of the metastatic carcinomas
The merit of high-frequency data in portfolio allocation
This paper addresses the open debate about the usefulness of high-frequency (HF) data in large-scale portfolio allocation. Daily covariances are estimated based on HF data of the S&P 500 universe employing a blocked realized kernel estimator. We propose forecasting covariance matrices using a multi-scale spectral decomposition where volatilities, correlation eigenvalues and eigenvectors evolve on different frequencies. In an extensive out-of-sample forecasting study, we show that the proposed approach yields less risky and more diversified portfolio allocations as prevailing methods employing daily data. These performance gains hold over longer horizons than previous studies have shown
Long-Read Sequencing to Unravel Complex Structural Variants of CEP78 Leading to Cone-Rod Dystrophy and Hearing Loss
Inactivating variants as well as a missense variant in the centrosomal CEP78 gene
have been identified in autosomal recessive cone-rod dystrophy with hearing loss
(CRDHL), a rare syndromic inherited retinal disease distinct from Usher syndrome.
Apart from this, a complex structural variant (SV) implicating CEP78 has been reported
in CRDHL. Here we aimed to expand the genetic architecture of typical CRDHL
by the identification of complex SVs of the CEP78 region and characterization of
their underlying mechanisms. Approaches used for the identification of the SVs are
shallow whole-genome sequencing (sWGS) combined with quantitative polymerase
chain reaction (PCR) and long-range PCR, or ExomeDepth analysis on whole-exome
sequencing (WES) data. Targeted or whole-genome nanopore long-read sequencing
(LRS) was used to delineate breakpoint junctions at the nucleotide level. For all SVs
cases, the effect of the SVs on CEP78 expression was assessed using quantitative
PCR on patient-derived RNA. Apart from two novel canonical CEP78 splice variants
and a frameshifting single-nucleotide variant (SNV), two SVs affecting CEP78 were
identified in three unrelated individuals with CRDHL: a heterozygous total gene deletion
of 235 kb and a partial gene deletion of 15 kb in a heterozygous and homozygous
state, respectively. Assessment of the molecular consequences of the SVs on patient’s
materials displayed a loss-of-function effect. Delineation and characterization of the 15-kb deletion using targeted LRS revealed the previously described complex CEP78
SV, suggestive of a recurrent genomic rearrangement. A founder haplotype was
demonstrated for the latter SV in cases of Belgian and British origin, respectively. The
novel 235-kb deletion was delineated using whole-genome LRS. Breakpoint analysis
showed microhomology and pointed to a replication-based underlying mechanism.
Moreover, data mining of bulk and single-cell human and mouse transcriptional datasets,
together with CEP78 immunostaining on human retina, linked the CEP78 expression
domain with its phenotypic manifestations. Overall, this study supports that the CEP78
locus is prone to distinct SVs and that SV analysis should be considered in a genetic
workup of CRDHL. Finally, it demonstrated the power of sWGS and both targeted
and whole-genome LRS in identifying and characterizing complex SVs in patients with
ocular diseases
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Linkage and association studies identify a novel locus for Alzheimer disease at 7q36 in a Dutch population-based sample
We obtained conclusive linkage of Alzheimer disease (AD) with a candidate region of 19.7 cM at 7q36 in an extended multiplex family, family 1270, ascertained in a population-based study of early-onset AD in the northern Netherlands. Single-nucleotide polymorphism and haplotype association analyses of a Dutch patient-control sample further supported the linkage at 7q36. In addition, we identified a shared haplotype at 7q36 between family 1270 and three of six multiplex AD-affected families from the same geographical region, which is indicative of a founder effect and defines a priority region of 9.3 cM. Mutation analysis of coding exons of 29 candidate genes identified one linked synonymous mutation, g.38030G-->C in exon 10, that affected codon 626 of the PAX transactivation domain interacting protein gene (PAXIP1). It remains to be determined whether PAXIP1 has a functional role in the expression of AD in family 1270 or whether another mutation at this locus explains the observed linkage and sharing. Together, our linkage data from the informative family 1270 and the association data in the population-based early-onset AD patient-control sample strongly support the identification of a novel AD locus at 7q36 and re-emphasize the genetic heterogeneity of AD
Characterization of Developmental Pathway of Natural Killer Cells from Embryonic Stem Cells In Vitro
In vitro differentiation of embryonic stem (ES) cells is often used to study hematopoiesis. However, the differentiation pathway of lymphocytes, in particular natural killer (NK) cells, from ES cells is still unclear. Here, we used a multi-step in vitro ES cell differentiation system to study lymphocyte development from ES cells, and to characterize NK developmental intermediates. We generated embryoid bodies (EBs) from ES cells, isolated CD34(+) EB cells and cultured them on OP9 stroma with a cocktail of cytokines to generate cells we termed ES-derived hematopoietic progenitors (ES-HPs). EB cell subsets, as well as ES-HPs derived from EBs, were tested for NK, T, B and myeloid lineage potentials using lineage specific cultures. ES-HPs derived from CD34(+) EBs differentiated into NK cells when cultured on OP9 stroma with IL-2 and IL-15, and into T cells on Delta-like 1-transduced OP9 (OP9-DL1) with IL-7 and Flt3-L. Among CD34(+) EB cells, NK and T cell potentials were detected in a CD45(−) subset, whereas CD45(+) EB cells had myeloid but not lymphoid potentials. Limiting dilution analysis of ES-HPs generated from CD34(+)CD45(−) EB cells showed that CD45(+)Mac-1(−)Ter119(−) ES-HPs are highly enriched for NK progenitors, but they also have T, B and myeloid potentials. We concluded that CD45(−)CD34(+) EB cells have lymphoid potential, and they differentiate into more mature CD45(+)Lin(−) hematopoietic progenitors that have lymphoid and myeloid potential. NK progenitors among ES-HPs are CD122(−) and they rapidly acquire CD122 as they differentiate along the NK lineage
Evaluation of Directed Graph-Mapping in Complex Atrial Tachycardias
Objectives: Directed graph-mapping (DGM) is a novel operator-independent automatic tool that can be applied to the identification of the atrial tachycardia (AT) mechanism. In the present study, for the first time, DGM was applied in complex AT cases, and diagnostic accuracy was evaluated. Background: Catheter ablation of ATs still represents a challenge, as the identification of the correct mechanism can be difficult. New algorithms for high-density activation mapping (HDAM) render an easier acquisition of more detailed maps; however, understanding of the mechanism and, thus, identification of the ablation targets, especially in complex cases, remains strongly operator-dependent. Methods: HDAMs acquired with the latest algorithm (COHERENT version 7, Biosense Webster, Irvine, California) were interpreted offline by 4 expert electrophysiologists, and the acquired electrode recordings with corresponding local activation times (LATs) were analyzed by DGM (also offline). Entrainment maneuvers (EM) were performed to understand the correct mechanism, which was then confirmed by successful ablation (13 cases were centrifugal, 10 cases were localized re-entry, 22 cases were macro–re-entry, and 6 were double-loops). In total, 51 ATs were retrospectively analyzed. We compared the diagnoses made by DGM were compared with those of the experts and with additional EM results. Results: In total, 51 ATs were retrospectively analyzed. Experts diagnosed the correct AT mechanism and location in 33 cases versus DGM in 38 cases. Diagnostic accuracy varied according to different AT mechanisms. The 13 centrifugal activation patterns were always correctly identified by both methods; 2 of 10 localized reentries were identified by the experts, whereas DGM diagnosed 7 of 10. For the macro–re-entries, 12 of 22 were correctly identified using HDAM versus 13 of 22 for DGM. Finally, 6 of 6 double-loops were correctly identified by the experts, versus 5 of 6 for DGM. Conclusions: Even in complex cases, DGM provides an automatic, fast, and operator-independent tool to identify the AT mechanism and location and could be a valuable addition to current mapping technologies. © 2021 The Authors.Dr. Lorenzo is an employee of Biosense Webster. Dr. Goedgebeur is funded with a research grant of the Research Foundation Flanders/Fonds voor Wetenschappelijk Onderzoek (FWO). Dr. Strisciuglio is supported by a research grant from the Cardiopath PhD program. Dr. el Haddad is a consultant for Biosense Webster. Dr. Duytschaever is a consultant for Biosense Webster. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose
Elevated plasma levels of cardiac troponin-I predict left ventricular systolic dysfunction in patients with myotonic dystrophy type 1:A multicentre cohort follow-up study
Objective:
High sensitivity plasma cardiac troponin-I (cTnI) is emerging as a strong predictor of cardiac events in a variety of settings. We have explored its utility in patients with myotonic dystrophy type 1 (DM1).
Methods:
117 patients with DM1 were recruited from routine outpatient clinics across three health boards. A single measurement of cTnI was made using the ARCHITECT STAT Troponin I assay. Demographic, ECG, echocardiographic and other clinical data were obtained from electronic medical records. Follow up was for a mean of 23 months.
Results:
Fifty five females and 62 males (mean age 47.7 years) were included. Complete data were available for ECG in 107, echocardiography in 53. Muscle Impairment Rating Scale score was recorded for all patients. A highly significant excess (p = 0.0007) of DM1 patients presented with cTnI levels greater than the 99th centile of the range usually observed in the general population (9 patients; 7.6%). Three patients with elevated troponin were found to have left ventricular systolic dysfunction (LVSD), compared with four of those with normal range cTnI (33.3% versus 3.7%; p = 0.001). Sixty two patients had a cTnI level < 5ng/L, of whom only one had documented evidence of LVSD. Elevated cTnI was not predictive of severe conduction abnormalities on ECG, or presence of a cardiac device, nor did cTnI level correlate with muscle strength expressed by Muscle Impairment Rating Scale score.
Conclusions:
Plasma cTnI is highly elevated in some ambulatory patients with DM1 and shows promise as a tool to aid cardiac risk stratification, possibly by detecting myocardial involvement. Further studies with larger patient numbers are warranted to assess its utility in this setting
Global burned area and biomass burning emissions from small fires
[1] In several biomes, including croplands, wooded savannas, and tropical forests, many small fires occur each year that are well below the detection limit of the current generation of global burned area products derived from moderate resolution surface reflectance imagery. Although these fires often generate thermal anomalies that can be detected by satellites, their contributions to burned area and carbon fluxes have not been systematically quantified across different regions and continents. Here we developed a preliminary method for combining 1-km thermal anomalies (active fires) and 500 m burned area observations from the Moderate Resolution Imaging Spectroradiometer (MODIS) to estimate the influence of these fires. In our approach, we calculated the number of active fires inside and outside of 500 m burn scars derived from reflectance data. We estimated small fire burned area by computing the difference normalized burn ratio (dNBR) for these two sets of active fires and then combining these observations with other information. In a final step, we used the Global Fire Emissions Database version 3 (GFED3) biogeochemical model to estimate the impact of these fires on biomass burning emissions. We found that the spatial distribution of active fires and 500 m burned areas were in close agreement in ecosystems that experience large fires, including savannas across southern Africa and Australia and boreal forests in North America and Eurasia. In other areas, however, we observed many active fires outside of burned area perimeters. Fire radiative power was lower for this class of active fires. Small fires substantially increased burned area in several continental-scale regions, including Equatorial Asia (157%), Central America (143%), and Southeast Asia (90%) during 2001–2010. Globally, accounting for small fires increased total burned area by approximately by 35%, from 345 Mha/yr to 464 Mha/yr. A formal quantification of uncertainties was not possible, but sensitivity analyses of key model parameters caused estimates of global burned area increases from small fires to vary between 24% and 54%. Biomass burning carbon emissions increased by 35% at a global scale when small fires were included in GFED3, from 1.9 Pg C/yr to 2.5 Pg C/yr. The contribution of tropical forest fires to year-to-year variability in carbon fluxes increased because small fires amplified emissions from Central America, South America and Southeast Asia—regions where drought stress and burned area varied considerably from year to year in response to El Nino-Southern Oscillation and other climate modes
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