| 1. |
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| 2. |
- Paie, Petra, et al.
(författare)
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Structured-light-sheet imaging in an integrated optofluidic platform
- 2023
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Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 24:1, s. 34-46
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Tidskriftsartikel (refereegranskat)abstract
- Heterogeneity investigation at the single-cell level reveals morphological and phenotypic characteristics in cell populations. In clinical research, heterogeneity has important implications in the correct detection and interpretation of prognostic markers and in the analysis of patient-derived material. Among single-cell analysis, imaging flow cytometry allows combining information retrieved by single cell images with the throughput of fluidic platforms. Nevertheless, these techniques might fail in a comprehensive heterogeneity evaluation because of limited image resolution and bidimensional analysis. Light sheet fluorescence microscopy opened new ways to study in 3D the complexity of cellular functionality in samples ranging from single-cells to micro-tissues, with remarkably fast acquisition and low photo-toxicity. In addition, structured illumination microscopy has been applied to single-cell studies enhancing the resolution of imaging beyond the conventional diffraction limit. The combination of these techniques in a microfluidic environment, which permits automatic sample delivery and translation, would allow exhaustive investigation of cellular heterogeneity with high throughput image acquisition at high resolution. Here we propose an integrated optofluidic platform capable of performing structured light sheet imaging flow cytometry (SLS-IFC). The system encompasses a multicolor directional coupler equipped with a thermo-optic phase shifter, cylindrical lenses and a microfluidic network to generate and shift a patterned light sheet within a microchannel. The absence of moving parts allows a stable alignment and an automated fluorescence signal acquisition during the sample flow. The platform enables 3D imaging of an entire cell in about 1 s with a resolution enhancement capable of revealing sub-cellular features and sub-diffraction limit details. The combination of structured illumination and light sheet fluorescence microscopy in a microfluidic integrated platform enables high throughput super-resolution imaging.
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| 3. |
- Stolk, Lisette, et al.
(författare)
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Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
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Tidskriftsartikel (refereegranskat)abstract
- To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
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| 4. |
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| 5. |
- Ballantyne, Kaye N., et al.
(författare)
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Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats
- 2014
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 35:8, s. 1021-1032
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Tidskriftsartikel (refereegranskat)abstract
- Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, greater than99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RMY-STRs in identifying and separating unrelated and related males and provides a reference database.
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| 6. |
- Battistoni, Giuseppe, et al.
(författare)
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Applications of FLUKA Monte Carlo code for nuclear and accelerator physics
- 2011
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Ingår i: Nuclear Instruments and Methods in Physics Research Section B. - : Elsevier BV. - 0168-583X .- 1872-9584. ; 269:24, s. 2850-2856
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Tidskriftsartikel (refereegranskat)abstract
- FLUKA is a general purpose Monte Carlo code capable of handling all radiation components from thermal energies (for neutrons) or 1 keV (for all other particles) to cosmic ray energies and can be applied in many different fields. Presently the code is maintained on Linux. The validity of the physical models implemented in FLUKA has been benchmarked against a variety of experimental data over a wide energy range, from accelerator data to cosmic ray showers in the Earth atmosphere. FLUKA is widely used for studies related both to basic research and to applications in particle accelerators, radiation protection and dosimetry, including the specific issue of radiation damage in space missions, radiobiology (including radiotherapy) and cosmic ray calculations.After a short description of the main features that make FLUKA valuable for these topics, the present paper summarizes some of the recent applications of the FLUKA Monte Carlo code in the nuclear as well high energy physics. In particular it addresses such topics as accelerator related applications.
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| 7. |
- Battistoni, Giuseppe, et al.
(författare)
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FLUKA Capabilities and CERN Applications for the Study of Radiation Damage to Electronics at High-Energy Hadron Accelerators
- 2011
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Konferensbidrag (refereegranskat)abstract
- The assessment of radiation damage to electronics is a complex process and requires a detailed description of the full particle energy spectra, as well as a clear characterization of the quantities used to predict radiation damage. FLUKA, a multi-purpose particle interaction and transport code, is capable of calculating proton-proton and heavy ion collisions at LHC energies and beyond. It correctly describes the entire hadronic and electromagnetic particle cascade initiated by secondary particles from TeV energies down to thermal neutrons, and provides direct scoring capabilities essential to estimate in detail the possible risk of radiation damage to electronics. This paper presents the FLUKA capabilities for applications related to radiation damage to electronics, providing benchmarking examples and showing the practical applications of FLUKA at CERN facilities such as CNGS and LHC. Related applications range from the study of device effects, the detailed characterization of the radiation field and radiation monitor calibration, to the input requirements for important mitigation studies including shielding, relocation or other options.
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| 8. |
- Battistoni, Giuseppe, et al.
(författare)
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The Application of the Monte Carlo Code FLUKA in Radiation Protection Studies for the Large Hadron Collider
- 2011
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Konferensbidrag (refereegranskat)abstract
- The multi-purpose particle interaction and transport code FLUKA is integral part of all radiation protection studies for the design and operation of the Large Hadron Collider (LHC) at CERN. It is one of the very few codes available for this type of calculations which is capable to calculate in one and the same simulation proton-proton and heavy ion collisions at LHC energies as well as the entire hadronic and electromagnetic particle cascade initiated by secondary particles in detectors and beam-line components from TeV energies down to energies of thermal neutrons. The present paper reviews these capabilities of FLUKA in sketching the relevant physics models along with examples ofradiation protection studies for the LHC such as shielding studies for underground areas occupied by personnel during LHC operation and the simulation of induced radioactivity around beam loss points. Integral part of the FLUKA development is a careful benchmarking of specific models as well as the code performance in actual, complex applications which is demonstrated with examples of studies relevant to radiation protection at the LHC.
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| 9. |
- Bi, Xiao Jun, et al.
(författare)
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Chapter 5 Dark Matter and New Physics Beyond the Standard Model with LHAASO
- 2022
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Ingår i: Chinese Physics C. - : IOP Publishing. - 1674-1137 .- 2058-6132. ; 46:3
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Tidskriftsartikel (refereegranskat)abstract
- In order to reveal the nature of dark matter, it is crucial to detect its non-gravitational interactions with the standard model particles. The traditional dark matter searches focused on the so-called weakly interacting massive particles. However, this paradigm is strongly constrained by the null results of current experiments with high precision. Therefore there is a renewed interest of searches for heavy dark matter particles above TeV scale. The Large High Altitude Air Shower Observatory (LHAASO) with large effective area and strong background rejection power is very suitable to investigate the gamma-ray signals induced by dark matter annihilation or decay above TeV scale. In this document, we review the theoretical motivations and background of heavy dark matter. We review the prospects of searching for the gamma-ray signals resulted from dark matter in the dwarf spheroidal satellites and Galactic halo for LHAASO, and present the projected sensitivities. We also review the prospects of searching for the axion-like particles, which are a kind of well motivated light pseudo-scalars, through the LHAASO measurement of the very high energy gamma-ray spectra of astrophysical sources.
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| 10. |
- Caforio, Alida L. P., et al.
(författare)
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Endomyocardial biopsy: safety and prognostic utility in paediatric and adult myocarditis in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry
- 2024
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Ingår i: EUROPEAN HEART JOURNAL. - 0195-668X .- 1522-9645.
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims Contemporary multicentre data on clinical and diagnostic spectrum and outcome in myocarditis are limited. Study aims were to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. Methods Five hundred eighty-one (68.0% male) patients, 493 adults, median age 38 (27-52) years, and 88 children, aged 8 (3-13) years, were divided into 3 groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance; Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no cardiac magnetic resonance. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes. Results Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on cardiac magnetic resonance was found in 31.3% of children and in 57.9% of adults with biopsy-proven myocarditis (P < .001). At 1-year follow-up, 11/410 patients (2.7%) died, 7 (1.7%) received a heart transplant, 3 underwent VAD (0.7%), and 16 (3.9%) underwent ICD implantation. Independent predictors at diagnosis of death or heart transplantation or hospitalization or VAD implantation or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non-aetiology-driven therapy. Conclusions Endomyocardial biopsy was safe, and cardiac magnetic resonance using Lake Louise criteria was less sensitive, particularly in children. Virus-negative lymphocytic myocarditis was predominant both in children and adults, and use of immunosuppressive treatments was low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis were independent predictors of unfavourable outcome events at 1 year.
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| 11. |
- Canals, Isaac, et al.
(författare)
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Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia
- 2023
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Ingår i: Brain Communications. - 2632-1297. ; 5:3, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is the second most prevalent type of early-onset dementia and up to 40% of cases are familial forms. One of the genes mutated in patients is CHMP2B, which encodes a protein found in a complex important for maturation of late endosomes, an essential process for recycling membrane proteins through the endolysosomal system. Here, we have generated a CHMP2B-mutated human embryonic stem cell line using genome editing with the purpose to create a human in vitro FTD disease model. To date, most studies have focused on neuronal alterations; however, we present a new co-culture system in which neurons and astrocytes are independently generated from human embryonic stem cells and combined in co-cultures. With this approach, we have identified alterations in the endolysosomal system of FTD astrocytes, a higher capacity of astrocytes to uptake and respond to glutamate, and a neuronal network hyperactivity as well as excessive synchronization. Overall, our data indicates that astrocyte alterations precede neuronal impairments and could potentially trigger neuronal network changes, indicating the important and specific role of astrocytes in disease development.
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| 12. |
- Elks, Cathy E, et al.
(författare)
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Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
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Tidskriftsartikel (refereegranskat)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
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| 13. |
- Komatsu, Kimberly J., et al.
(författare)
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Global change effects on plant communities are magnified by time and the number of global change factors imposed
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:36, s. 17867-17873
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Tidskriftsartikel (refereegranskat)abstract
- Accurate prediction of community responses to global change drivers (GCDs) is critical given the effects of biodiversity on ecosystem services. There is consensus that human activities are driving species extinctions at the global scale, but debate remains over whether GCDs are systematically altering local communities worldwide. Across 105 experiments that included over 400 experimental manipulations, we found evidence for a lagged response of herbaceous plant communities to GCDs caused by shifts in the identities and relative abundances of species, often without a corresponding difference in species richness. These results provide evidence that community responses are pervasive across a wide variety of GCDs on long-term temporal scales and that these responses increase in strength when multiple GCDs are simultaneously imposed.Global change drivers (GCDs) are expected to alter community structure and consequently, the services that ecosystems provide. Yet, few experimental investigations have examined effects of GCDs on plant community structure across multiple ecosystem types, and those that do exist present conflicting patterns. In an unprecedented global synthesis of over 100 experiments that manipulated factors linked to GCDs, we show that herbaceous plant community responses depend on experimental manipulation length and number of factors manipulated. We found that plant communities are fairly resistant to experimentally manipulated GCDs in the short term (<10 y). In contrast, long-term (≥10 y) experiments show increasing community divergence of treatments from control conditions. Surprisingly, these community responses occurred with similar frequency across the GCD types manipulated in our database. However, community responses were more common when 3 or more GCDs were simultaneously manipulated, suggesting the emergence of additive or synergistic effects of multiple drivers, particularly over long time periods. In half of the cases, GCD manipulations caused a difference in community composition without a corresponding species richness difference, indicating that species reordering or replacement is an important mechanism of community responses to GCDs and should be given greater consideration when examining consequences of GCDs for the biodiversity–ecosystem function relationship. Human activities are currently driving unparalleled global changes worldwide. Our analyses provide the most comprehensive evidence to date that these human activities may have widespread impacts on plant community composition globally, which will increase in frequency over time and be greater in areas where communities face multiple GCDs simultaneously.
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| 14. |
- Lunetta, Kathryn L., et al.
(författare)
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Rare coding variants and X-linked loci associated with age at menarche
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only similar to 3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency proteincoding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P<5 x 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P = 9.4 x 10(-13)) and FAAH2 (rs5914101, P = 4.9 x 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P = 2.8 x 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain similar to 0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.
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| 15. |
- Malits, Andrea, et al.
(författare)
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Viral-Mediated Microbe Mortality Modulated by Ocean Acidification and Eutrophication : Consequences for the Carbon Fluxes Through the Microbial Food Web
- 2021
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Anthropogenic carbon emissions are causing changes in seawater carbonate chemistry including a decline in the pH of the oceans. While its aftermath for calcifying microbes has been widely studied, the effect of ocean acidification (OA) on marine viruses and their microbial hosts is controversial, and even more in combination with another anthropogenic stressor, i.e., human-induced nutrient loads. In this study, two mesocosm acidification experiments with Mediterranean waters from different seasons revealed distinct effects of OA on viruses and viral-mediated prokaryotic mortality depending on the trophic state and the successional stage of the plankton community. In the winter bloom situation, low fluorescence viruses, the most abundant virus-like particle (VLP) subpopulation comprising mostly bacteriophages, were negatively affected by lowered pH with nutrient addition, while the bacterial host abundance was stimulated. High fluorescence viruses, containing cyanophages, were stimulated by OA regardless of the nutrient conditions, while cyanobacteria of the genus Synechococcus were negatively affected by OA. Moreover, the abundance of very high fluorescence viruses infecting small haptophytes tended to be lower under acidification while their putative hosts' abundance was enhanced, suggesting a direct and negative effect of OA on viral-host interactions. In the oligotrophic summer situation, we found a stimulating effect of OA on total viral abundance and the viral populations, suggesting a cascading effect of the elevated pCO(2) stimulating autotrophic and heterotrophic production. In winter, viral lysis accounted for 30 +/- 16% of the loss of bacterial standing stock per day (VMMBSS) under increased pCO(2) compared to 53 +/- 35% in the control treatments, without effects of nutrient additions while in summer, OA had no significant effects on VMMBSS (35 +/- 20% and 38 +/- 5% per day in the OA and control treatments, respectively). We found that phage production and resulting organic carbon release rates significantly reduced under OA in the nutrient replete winter situation, but it was also observed that high nutrient loads lowered the negative effect of OA on viral lysis, suggesting an antagonistic interplay between these two major global ocean stressors in the Anthropocene. In summer, however, viral-mediated carbon release rates were lower and not affected by lowered pH. Eutrophication consistently stimulated viral production regardless of the season or initial conditions. Given the relevant role of viruses for marine carbon cycling and the biological carbon pump, these two anthropogenic stressors may modulate carbon fluxes through their effect on viruses at the base of the pelagic food web in a future global change scenario.
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| 16. |
- Mantovani, Vittorio, 1965, et al.
(författare)
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Microdialysis for myocardial metabolic surveillance: developing a clinical technique.
- 2006
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Ingår i: Clinical physiology and functional imaging. - 1475-0961. ; 26:4, s. 224-31
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic surveillance of the myocardium is of great interest in cardiac surgery. Microdialysis allows sampling of chemical substances from the interstitial fluid for immediate analysis. The two objectives of this study were to develop a technique for simple and safe implantation of a commercially available microdialysis probe (CMA-70) into the myocardium and to obtain reference data for further use and metabolic control. Eighteen pigs were used in an experimental ischaemic heart model where the left anterior descending coronary artery was occluded for 20 min. Microdialysis was performed proximally as well as distally to the arterial occlusion site corresponding to a control and an ischaemic area in the heart. Two techniques were tried for probe implantation, using either a pacemaker wire attached to the probe tip or a needle introducer. Metabolic substrates (glucose, lactate, glycerol and pyruvate) were collected before, during and after ischaemia, for up to 6 h. Both techniques were highly effective in registering metabolic changes due to ischaemia with sharp time resolution, but the needle introducer was superior regarding probe durability. It is concluded that the CMA-70 microdialysis probe implanted with the needle introducer allows for an accurate monitoring of myocardial metabolism during a prolonged period of time. Future studies in the human heart are warranted to further validate the technique.
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| 17. |
- Mantovani, Vittorio, et al.
(författare)
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Myocardial metabolism assessed by microdialysis: a prospective randomized study in on- and off-pump coronary bypass surgery.
- 2010
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 143:3, s. 302-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of the study was to compare energetic metabolism in the myocardium during coronary surgery with and without cardiopulmonary bypass by means of microdialysis. METHODS: Twenty-six low-risk patients were prospectively randomized to off-pump versus on-pump surgery. Microdialysis was used to sample myocardial interstitial fluid during and for 23hours after surgery. RESULTS: Preoperative characteristics and clinical outcome were similar in both groups. Blood glucose and lactate did not differ between groups throughout the observation time. During surgery, intramyocardial levels of glucose, pyruvate and urea were unaffected in off-pump patients, while the same substances significantly decreased (p<0.05) in on-pump patients during cardioplegic arrest, and increased during reperfusion. Interstitial lactate levels were higher during off-pump surgery (p<0.05). From 3 to 15hours after surgery, intramyocardial concentrations of glucose, urea and lactate were higher in off-pump patients (p<0.001), while pyruvate was higher in on-pump patients (p<0.01). Intramyocardial lactate/pyruvate ratio never differed between groups. Postoperatively, cumulative blood release of troponin-T was significantly higher in the on-pump group (p<0.005). CONCLUSIONS: Microdialysis could demonstrate significant differences in energetic metabolism between the two groups. Our data confirm and might help in explaining the lower release of myocardial ischemic markers after off-pump surgery.
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| 18. |
- Mariscalco, Giovanni, et al.
(författare)
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Relationship between atrial histopathology and atrial fibrillation after coronary bypass surgery
- 2006
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Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Mosby Inc.. - 0022-5223 .- 1097-685X. ; 131:6, s. 1364-1372
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Postoperative atrial fibrillation is common after coronary surgery. The cellular condition of atrial myocytes might play a part in the postoperative development of atrial fibrillation. Our study aimed to investigate whether patients in whom postoperative atrial fibrillation develops show pre-existent alterations in histopathology of the right atrium and how such changes are expressed in relation to the use of cardiopulmonary bypass.METHODS: Seventy patients undergoing elective coronary revascularization were prospectively randomized to on-pump conventional surgery (conventional coronary artery bypass grafting, n = 35) or off-pump surgery on the beating heart (off-pump coronary artery bypass grafting, n = 35). Samples from the right atrial appendage were immediately collected after opening the pericardium. In the on-pump group samples were also taken after weaning from cardiopulmonary bypass. Focusing on degenerative alterations, histology was studied by means of light microscopy and for confirmation of particular findings by means of electronic microscopy.RESULTS: Twenty-two (31%) patients had postoperative atrial fibrillation, with the rate not being different between the off-pump coronary artery bypass grafting and conventional coronary artery bypass grafting groups (P = .797). Left atrial enlargement and inotropic requirement were related to atrial fibrillation. Interstitial fibrosis, vacuolization, and nuclear derangement of myocytes were the histologic abnormalities associated with the development of postoperative atrial fibrillation. However, in multivariate analysis fibrosis was confounded by myocyte vacuolization (P = .002) and nuclear derangement (P = .016), representing independent atrial fibrillation predictors. As expected, the conventional coronary artery bypass grafting and off-pump coronary artery bypass grafting groups showed similar histology, but more importantly, no atrial changes were detected in relation to cardiopulmonary bypass exposure in the conventional coronary artery bypass grafting group. Atrial histology showed degenerative changes that correlated with advanced age and left atrial enlargement.CONCLUSIONS: Our study supports the contention that atrial fibrillation after coronary surgery is associated with pre-existing histopathologic changes of the right atrium. Patients randomly allocated to off-pump coronary artery bypass grafting procedures showed a similar rate of atrial fibrillation and a similar relationship to atrial histology as did those exposed to cardiopulmonary bypass. Cardiopulmonary bypass did not cause additional changes in tested histology variables.
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| 19. |
- Mariscalco, Giovanni, et al.
(författare)
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Transthoracic echocardiography is adequate for the diagnosis of right coronary artery aneurysms
- 2008
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Ingår i: Journal of cardiac surgery. - : Wiley-Blackwell. - 0886-0440 .- 1540-8191. ; 23:1, s. 72-74
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Tidskriftsartikel (refereegranskat)abstract
- Coronary artery aneurysms (CAA) are rare but potentially fatal pathologies. This case was referred to our Unit after occasional echocardiographic finding of an intracardiac mass. A new detailed transthoracic echocardiogram was decisive for a diagnosis of a large CAA of the right coronary artery, compressing and dislocating the right atrium. Transesophageal echocardiography was not performed because of the data obtained. The diagnosis was confirmed by cardiac catheterization. The patient was managed with a surgical procedure.
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| 20. |
- McCarthy, Shane, et al.
(författare)
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A reference panel of 64,976 haplotypes for genotype imputation
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1279-1283
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Tidskriftsartikel (refereegranskat)abstract
- We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently.
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| 21. |
- Wessel, Jennifer, et al.
(författare)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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| 22. |
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