| 1. |
- Murari, A., et al.
(författare)
-
A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
-
Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Marhold, Karol, et al.
(författare)
-
IAPT chromosome data 39-Extended version
- 2023
-
Ingår i: Taxon. - : John Wiley & Sons. - 0040-0262 .- 1996-8175. ; 72:5, s. 1189-1192
-
Tidskriftsartikel (refereegranskat)
|
|
| 5. |
- Apollonio, Benedetta, et al.
(författare)
-
Tumor-activated lymph node fibroblasts suppress T cell function in diffuse large B cell lymphoma
- 2023
-
Ingår i: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 133:13
-
Tidskriftsartikel (refereegranskat)abstract
- Recent transcriptomic-based analysis of diffuse large B cell lymphoma (DLBCL) has highlighted the clinical relevance of LN fibroblast and tumor-infiltrating lymphocyte (TIL) signatures within the tumor microenvironment (TME). However, the immunomodulatory role of fibroblasts in lymphoma remains unclear. Here, by studying human and mouse DLBCL-LNs, we identified the presence of an aberrantly remodeled fibroblastic reticular cell (FRC) network expressing elevated fibroblast activated protein (FAP). RNA-Seq analyses revealed that exposure to DLBCL reprogrammed key immunoregulatory pathways in FRCs, including a switch from homeostatic to inflammatory chemokine expression and elevated antigen-presentation molecules. Functional assays showed that DLBCL-activated FRCs (DLBCL-FRCs) hindered optimal TIL and chimeric antigen receptor (CAR) T cell migration. Moreover, DLBCL-FRCs inhibited CD'+ TIL cytotoxicity in an antigen-specific manner. Notably, the interrogation of patient LNs with imaging mass cytometry identified distinct environments differing in their CD'+ TIL-FRC composition and spatial organization that associated with survival outcomes. We further demonstrated the potential to target inhibitory FRCs to rejuvenate interacting TILs. Cotreating organotypic cultures with FAP-targeted immunostimulatory drugs and a bispecific antibody (glofitamab) augmented antilymphoma TIL cytotoxicity. Our study reveals an immunosuppressive role of FRCs in DLBCL, with implications for immune evasion, disease pathogenesis, and optimizing immunotherapy for patients.
|
|
| 6. |
- Boman, Kurt, et al.
(författare)
-
Healthcare resource utilization associated with heart failure with preserved versus reduced ejection fraction : a retrospective population-based cohort study in Sweden
- 2017
-
Ingår i: European Journal of Heart Failure. - : European Society of Cardiology. - 1388-9842 .- 1879-0844. ; 19:S1, s. 346-346
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: To estimate healthcare resource utilization among patients with heart failure (HF) with preserved (HFpEF) versus reduced (HFrEF) ejection fraction using population data from two Swedish counties.Methods: Patients with HF were identified via electronic medical records (EMRs) from primary and/or secondary care in Uppsala and Västerbotten, linked via unique identifiers to data from the National Patient Register and Swedish Prescribed Drug Register. Local echocardiography data were used to identify HFpEF (defined as ejection fraction ≥50%) and HFrEF (defined as <50%). Patients aged ≥18 years with ≥2 diagnoses of HF between 01/01/2010 and 31/03/2015 and an ICD-10 diagnostic code of I50 (inclusive of all granular codes), I42.0, I42.6, I42.7, I42.9, I110, I130 or I132 in any position were included. Patients were followed from date of first diagnosis (index date) to end of study period or EMR collection, date of death or loss to follow-up for other reasons, whichever came first. Unadjusted all-cause and cardiovascular disease (CVD)-related hospitalization rates were assessed using a Cox proportional hazards model, accounting for age, sex, setting of first diagnosis (primary vs secondary care), HF phenotype and NT-proBNP level.Results: In total, 8702 patients with HF were identified. HF phenotype was known in 3167 patients; 64.6% had HFrEF, 35.4% had HFpEF. Patients with HFrEF were younger (mean±SD: 69.9±13.7 vs 74.2±12.6 years) with a lower Charlson comorbidity index (1.65 vs 1.83) than those with HFpEF. All-cause hospitalization rates were marginally lower for HFrEF than for HFpEF (mean [95% CI] proportion of patients hospitalized within 1 year of diagnosis, 72.5 [70.1–74.8]% vs 73.8 [70.7–77.0]%; hazard ratio [HR] over whole follow-up period, 0.87 [0.79–0.97], p=0.0093). The proportion of patients hospitalized was higher for those diagnosed in secondary care than in primary care, particularly within 1 year of diagnosis (1-year rate, 69.6 [68.3–71.0]% vs 59.1 [56.8–61.4]%; HR, 1.15 [1.07–1.23], p=0.0002). Similar trends were observed for CVD-related hospitalization rates for HFrEF vs HFpEF (1-year rate, 69.5 [67.1–71.9]% vs 70.7 [67.5–74.0]%; HR, 0.89 [0.81–0.99], p=0.0309) and for patients diagnosed in secondary vs primary care (1-year rate, 66.6 [65.3–68.0]% vs 56.2 [53.8–58.5]%; HR, 1.15 [1.07–1.24], p=0.0001). Numbers of hospitalizations and outpatient visits decreased with time after diagnosis for HFrEF, but increased slightly for HFpEF after 2 years (Figure). The mean±SD total number of all-cause days of hospitalization during the first year after diagnosis was lower in patients with HFrEF vs HFpEF (19.9±26.1 vs 26.3±34.5 days), while the number of HF-related days of hospitalization was similar (16.0±22.4 vs 17.2±24.0 days).Conclusions: Number and duration of hospital stays were significantly lower over time in patients with HFrEF than HFpEF; this may be explained by the comorbidity burden in the latter group.
|
|
| 7. |
|
|
| 8. |
- Frye, Maike, et al.
(författare)
-
Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program
- 2018
-
Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Tissue and vessel wall stiffening alters endothelial cell properties and contributes to vascular dysfunction. However, whether extracellular matrix (ECM) stiffness impacts vascular development is not known. Here we show that matrix stiffness controls lymphatic vascular morphogenesis. Atomic force microscopy measurements in mouse embryos reveal that venous lymphatic endothelial cell (LEC) progenitors experience a decrease in substrate stiffness upon migration out of the cardinal vein, which induces a GATA2-dependent transcriptional program required to form the first lymphatic vessels. Transcriptome analysis shows that LECs grown on a soft matrix exhibit increased GATA2 expression and a GATA2-dependent upregulation of genes involved in cell migration and lymphangiogenesis, including VEGFR3. Analyses of mouse models demonstrate a cell-autonomous function of GATA2 in regulating LEC responsiveness to VEGF-C and in controlling LEC migration and sprouting in vivo. Our study thus uncovers a mechanism by which ECM stiffness dictates the migratory behavior of LECs during early lymphatic development.
|
|
| 9. |
- Morini, Marco F., et al.
(författare)
-
VE-Cadherin-Mediated Epigenetic Regulation of Endothelial Gene Expression
- 2018
-
Ingår i: Circulation Research. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7330 .- 1524-4571. ; 122:2, s. 231-245
-
Tidskriftsartikel (refereegranskat)abstract
- Rationale: The mechanistic foundation of vascular maturation is still largely unknown. Several human pathologies are characterized by deregulated angiogenesis and unstable blood vessels. Solid tumors, for instance, get their nourishment from newly formed structurally abnormal vessels which present wide and irregular interendothelial junctions. Expression and clustering of the main endothelial-specific adherens junction protein, VEC (vascular endothelial cadherin), upregulate genes with key roles in endothelial differentiation and stability.Objective: We aim at understanding the molecular mechanisms through which VEC triggers the expression of a set of genes involved in endothelial differentiation and vascular stabilization.Methods and Results: We compared a VEC-null cell line with the same line reconstituted with VEC wild-type cDNA. VEC expression and clustering upregulated endothelial-specific genes with key roles in vascular stabilization including claudin-5, vascular endothelial-protein tyrosine phosphatase (VE-PTP), and von Willebrand factor (vWf). Mechanistically, VEC exerts this effect by inhibiting polycomb protein activity on the specific gene promoters. This is achieved by preventing nuclear translocation of FoxO1 (Forkhead box protein O1) and beta-catenin, which contribute to PRC2 (polycomb repressive complex-2) binding to promoter regions of claudin-5, VE-PTP, and vWf. VEC/beta-catenin complex also sequesters a core subunit of PRC2 (Ezh2 [enhancer of zeste homolog 2]) at the cell membrane, preventing its nuclear translocation. Inhibition of Ezh2/VEC association increases Ezh2 recruitment to claudin-5, VE-PTP, and vWf promoters, causing gene downregulation. RNA sequencing comparison of VEC-null and VEC-positive cells suggested a more general role of VEC in activating endothelial genes and triggering a vascular stability-related gene expression program. In pathological angiogenesis of human ovarian carcinomas, reduced VEC expression paralleled decreased levels of claudin-5 and VE-PTP.Conclusions: These data extend the knowledge of polycomb-mediated regulation of gene expression to endothelial cell differentiation and vessel maturation. The identified mechanism opens novel therapeutic opportunities to modulate endothelial gene expression and induce vascular normalization through pharmacological inhibition of the polycomb-mediated repression system.
|
|
| 10. |
- Nabais, F., et al.
(författare)
-
Bump-on-tail distributions caused by Alfvénic redistribution of energetic ions
- 2022
-
Ingår i: Nuclear Fusion. - : Institute of Physics Publishing (IOPP). - 0029-5515 .- 1741-4326. ; 62:10
-
Tidskriftsartikel (refereegranskat)abstract
- A series of experiments was performed in the JET tokamak aiming to study the characteristics and eventual effects of beam injected ion populations further accelerated through 2nd harmonic ion cyclotron heating. It was found that the injection of these ions could affect sawtooth stability and that these populations excite toroidicity induced Alfvén eigenmodes (TAEs) in the core of the plasma. More interestingly, measurements of DD beam-plasma neutrons from the TOFOR spectrometer show that these modes caused local bump-on-tail distributions in energy. Numerical simulations performed with the CASTOR-K code found a strong interaction between the core-localized TAEs and ions with energies at which local minima in the energy distribution were measured.
|
|
| 11. |
- Olofsson, Mona, et al.
(författare)
-
A description of characteristics of very elderly patients newly diagnosed with heart failure : a retrospective population-based cohort study in Sweden
- 2017
-
Ingår i: European Journal of Heart Failure. - : European Society of Cardiology. - 1388-9842 .- 1879-0844. ; 19:S1, s. 362-362
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Over a quarter of patients with heart failure (HF) in Sweden are very elderly (defined as aged ≥85 years). Evidence on the demographic and clinical characteristics of these patients, and on the diagnostic procedures they receive in clinical practice, is scarce.Methods: Patients with HF were identified via electronic medical records from primary and/or secondary care in Västerbotten, linked via unique identifiers to data from the National Patient Register and Swedish Prescribed Drug Register. Local echocardiography data were used to identify patients with HF with preserved (HFpEF, ≥50%) and reduced (HFrEF, <50%) ejection fraction. Patients aged ≥18 years with ≥2 diagnoses of HF between 01/01/2010 and 31/03/2015 and an ICD-10 diagnostic code of I50 (inclusive of all granular codes), I42.0, I42.6, I42.7, I42.9, I110, I130 or I132 in any position were included. The date of the first diagnosis was the index date. ICD-10 codes were also used to identify comorbidities. A 10-year look-back period was used to exclude prevalent HF cases. Patient characteristics were assessed at index, except comorbidities (in the 5 years before index) and pre-diagnosis comedications (in the first year before index).Results: In total, 8702 patients with HF were identified; 27.7% were aged ≥85 years. Compared with patients <85 years, more patients ≥85 years were female (60.2% vs 40.6%) and fewer were overweight (BMI >25 kg/m2, 42.3% vs 63.5%). In both groups, HF was more commonly diagnosed in secondary than in primary care, but patients ≥85 years were more often diagnosed in primary care than those <85 years (31.2% vs 20.9%). Fewer patients ≥85 years than those <85 years received an echocardiogram at diagnosis (19.3% vs 42.9%); of those who did, more patients ≥85 years than <85 years had HFpEF (46.8% vs 33.4%). Patients ≥85 years had a comorbidity burden similar to those <85 years (mean number of comorbidities/patient, 2.4 vs 2.3); prevalence of atrial fibrillation (32.0% vs 30.4%), hypertension (53.2% vs 53.0%) and ischaemic heart disease (20.5% vs 22.5%) were also similar in both age groups. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and systolic blood pressure (BP) increased with age, and diastolic BP and estimated glomerular filtration rate decreased. Potassium and sodium levels did not differ between age groups (Table). The most common pre-diagnosis comedications were ?-blockers, antithrombotic agents and diuretics; ?-blockers were less frequently prescribed in patients ≥85 years (59.6% vs 64.4%), and antithrombotic agents and diuretics were more frequently prescribed in those ≥85 years (antithrombotic agents, 57.0% vs 54.3%; diuretics, 50.1% vs 43.1%).Conclusions: Very elderly patients with HF in Sweden are clinically different from younger patients, with a higher prevalence of HFpEF and higher NT-proBNP levels (as expected). Most importantly, very elderly patients seldom receive an echocardiogram at diagnosis.
|
|
| 12. |
|
|
| 13. |
- Strömberg, Anna, 1967-, et al.
(författare)
-
Psychometric Validation of the Heart Failure Caregiver Questionnaire (HF-CQ (R))
- 2017
-
Ingår i: Patient. - : ADIS INT LTD. - 1178-1653 .- 1178-1661. ; 10:5, s. 579-592
-
Tidskriftsartikel (refereegranskat)abstract
- Background The Heart Failure Caregiver Questionnaire (HF-CQ (R)) was developed to assess subjective outcomes of heart failure caregivers. The HF-CQ (R) comprises 21 questions on three domains, namely physical, emotional/psychological and lifestyle. The objective of this study was to evaluate the psychometric properties of the HF-CQ (R). Methods Patients (n = 150) with heart failure and their primary caregivers (n = 150) were recruited from 11 sites in USA. Caregivers completed the HF-CQ (R) and additional questionnaires, namely Caregiver Reaction Assessment, Work Productivity and Activity Impairment questionnaire, EuroQol-5 domain, and the Hospital Anxiety and Depression Scale. Patient-completed Global Impression of Severity, construct validity, concurrent validity, reliability and responsiveness of the HF-CQ (R) were also assessed. Results In the physical and lifestyle domains, all items showed acceptable validity. No high correlations between HF-CQ (R) scores and other caregiver-completed instruments, including the Hospital Anxiety and Depression Scale, Work Productivity and Activity Impairment questionnaire, EuroQol-5 domain or Caregiver Reaction Assessment, were reported. The intra-class correlation coefficient exceeded the threshold for reliability (amp;gt;0.7) across the physical well-being (0.785), emotional/psychological (0.797), lifestyle (0.787) and total scores (0.850), indicating acceptable reliability. Internal consistency results using Cronbachs alpha showed the total aggregate score of 0.942 to be reliable. In the responsiveness analyses, each of the three scales and the total score showed responsiveness to changes defined by the Caregiver Global Impression of Severity. The overall caregiver burden score increased with increased severity of illness in the cared-for patients. Conclusions The study provides initial evidence for the acceptable validity of the HF-CQ (R) as an instrument to measure heart failure caregiver burden.
|
|
| 14. |
|
|
| 15. |
|
|
