| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Thomas, HS, et al.
(författare)
-
- 2019
-
swepub:Mat__t
|
|
| 5. |
|
|
| 6. |
- Gregson, J., et al.
(författare)
-
Cardiovascular Risk Factors Associated With Venous Thromboembolism
- 2019
-
Ingår i: JAMA Cardiology. - : American Medical Association (AMA). - 0965-2590 .- 2380-6583 .- 2380-6591. ; 4:2, s. 163-173
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). OBJECTIVE To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. DESIGN, SETTING, AND PARTICIPANTS This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CND], 25131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). RESULTS Of the 731728 participants from the ERFC. 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. CONCLUSIONS AND RELEVANCE Older age, smoking, and adiposity were consistently associated with higher VTE risk.
|
|
| 7. |
- Ademuyiwa, Adesoji O., et al.
(författare)
-
Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
-
Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Seiler, Roland, et al.
(författare)
-
Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy
- 2017
-
Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 72:4, s. 544-554
-
Tidskriftsartikel (refereegranskat)abstract
- Background: An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype. Objective: To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC. Design, setting, and participants: Whole transcriptome profiling was performed on pre-NAC transurethral resection specimens from 343 patients with MIBC. Samples were classified according to four published molecular subtyping methods. We developed a single-sample genomic subtyping classifier (GSC) to predict consensus subtypes (claudin-low, basal, luminal-infiltrated and luminal) with highest clinical impact in the context of NAC. Overall survival (OS) according to subtype was analyzed and compared with OS in 476 non-NAC cases (published datasets). Intervention: Gene expression analysis was used to assign subtypes. Outcome measurements and statistical analysis: Receiver-operating characteristics were used to determine the accuracy of GSC. The effect of GSC on survival was estimated by Cox proportional hazard regression models. Results and limitations: The models generated subtype calls in expected ratios with high concordance across subtyping methods. GSC was able to predict four consensus molecular subtypes with high accuracy (73%), and clinical significance of the predicted consensus subtypes could be validated in independent NAC and non-NAC datasets. Luminal tumors had the best OS with and without NAC. Claudin-low tumors were associated with poor OS irrespective of treatment regimen. Basal tumors showed the most improvement in OS with NAC compared with surgery alone. The main limitations of our study are its retrospective design and comparison across datasets. Conclusions: Molecular subtyping may have an impact on patient benefit to NAC. If validated in additional studies, our results suggest that patients with basal tumors should be prioritized for NAC. We discovered the first single-sample classifier to subtype MIBC, which may be suitable for integration into routine clinical practice. Patient summary: Different molecular subtypes can be identified in muscle-invasive bladder cancer. Although cisplatin-based neoadjuvant chemotherapy improves patient outcomes, we identified that the benefit is highest in patients with basal tumors. Our newly discovered classifier can identify these molecular subtypes in a single patient and could be integrated into routine clinical practice after further validation. Molecular subtypes in muscle-invasive bladder cancer appear have an impact on patient response to neoadjuvant chemotherapy (NAC); namely, patients with basal tumors showed the most benefit from NAC and should be prioritized for NAC. Moreover, these subtypes can be identified in a single sample by our discovered classifier.
|
|
| 11. |
- Anastasopoulos, M., et al.
(författare)
-
Multi-Grid detector for neutron spectroscopy : Results obtained on time-of-flight spectrometer CNCS
- 2017
-
Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12:4
-
Tidskriftsartikel (refereegranskat)abstract
- The Multi-Grid detector technology has evolved from the proof-of-principle and characterisation stages. Here we report on the performance of the Multi-Grid detector, the MG.CNCS prototype, which has been installed and tested at the Cold Neutron Chopper Spectrometer, CNCS at SNS. This has allowed a side-by-side comparison to the performance of 3He detectors on an operational instrument. The demonstrator has an active area of 0.2 m2. It is specifically tailored to the specifications of CNCS. The detector was installed in June 2016 and has operated since then, collecting neutron scattering data in parallel to the He-3 detectors of CNCS. In this paper, we present a comprehensive analysis of this data, in particular on instrument energy resolution, rate capability, background and relative efficiency. Stability, gamma-ray and fast neutron sensitivity have also been investigated. The effect of scattering in the detector components has been measured and provides input to comparison for Monte Carlo simulations. All data is presented in comparison to that measured by the 3He detectors simultaneously, showing that all features recorded by one detector are also recorded by the other. The energy resolution matches closely. We find that the Multi-Grid is able to match the data collected by 3He, and see an indication of a considerable advantage in the count rate capability. Based on these results, we are confident that the Multi-Grid detector will be capable of producing high quality scientific data on chopper spectrometers utilising the unprecedented neutron flux of the ESS.
|
|
| 12. |
|
|
| 13. |
- Ehlers, G., et al.
(författare)
-
Neutron xyz - polarization analysis at a time-of-flight instrument
- 2015
-
Ingår i: QENS/WINS 2014 - 11th International Conference on Quasielastic Neutron Scattering and 6th International Workshopon Inelastic Neutron Spectrometers. - : EDP Sciences. - 2101-6275 .- 2100-014X. ; 83, s. 03004-03004
-
Konferensbidrag (refereegranskat)abstract
- When implementing a dedicated polarization analysis setup at a neutron time-of-flight instrument with a large area detector, one faces enormous challenges. Nevertheless, significant progress has been made towards this goal over the last few years. This paper addresses systematic limitations of the traditional method that is used to make these measurements, and a possible strategy to overcome these limitations. This will be important, for diffraction as well as inelastic experiments, where the scattering occurs mostly out-of-plane.
|
|
| 14. |
- Melero-Fernandez de Mera, R. M., et al.
(författare)
-
Effects of mutations in the post-translational modification sites on the trafficking of hyaluronan synthase 2 (HAS2)
- 2019
-
Ingår i: Matrix Biology. - : Elsevier BV. - 0945-053X .- 1569-1802. ; 80, s. 85-103
-
Tidskriftsartikel (refereegranskat)abstract
- Vesicular trafficking of hyaluronan synthases (HAS1-3) from endoplasmic reticulum (ER) through Golgi to plasma membrane (PM), and either back to endosomes and lysosomes, or out into extracellular vesicles, is important for their activities. We studied how post-translational modifications affect the trafficking of HAS2 by mutagenesis of the sites of ubiquitination (K190R), phosphorylation (T110A) and 0-GIcNAcylation (S221A), using Dendra2- and EGFP-HAS2 transfected into COS1 cells. Confocal microscopy showed HAS2 wild type (wt) and its K19OR and S221A mutants in ER, Golgi and extracellular vesicles, while the T110A mutant remained mostly in the ER. HA synthesis was reduced by S221A, while completely blocked by K19OR and T110A. Cell-surface biotinylation indicated that T110A was absent from PM, while S221A was close to the level of wt, and K190R was increased in PM. TIRF microscopy analysis gave similar results. Rabl 0 silencing increased HA secretion by HAS2, likely by inhibiting endocytosis of the enzyme from PM, as reported before for HAS3. Green-to-red photo-conversion of Dendra2-HAS2 constructs suggested slower decay of K190R and S221A than HAS2 wt, while T110A was barely degraded at all. S221D and S221E, the phosphomimetic mutants of this site, decayed faster and blocked hyaluronan synthesis, suggesting alternative 0-GIcNAci-PO4 substitution to regulate the stability of the enzyme. Probing the role of dynamic 0-GIcNAcylation at S221 by adding glucosamine increased the half-life of only HAS2 wt. The Dendra2 " HAS2 disappearance from Golgi was slower for K190R. Of the two inactive constructs, K190R co-transfected with HAS2 wt suppressed, whereas T110A had no effect on HA synthesis. Interestingly, the HAS2stimulated shedding of extracellular vesicles was dependent on HAS residence in PM but independent of HA synthesis. The results indicate that post-translational modifications control the trafficking of HAS2, and that trafficking is an integral part of the post-translational regulation of HAS2 activity.
|
|
| 15. |
- Portnichenko, P. Y., et al.
(författare)
-
Momentum-space structure of quasielastic spin fluctuations in Ce3Pd20Si6
- 2015
-
Ingår i: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 91:9
-
Tidskriftsartikel (refereegranskat)abstract
- Among heavy-fermion metals, Ce3Pd20Si6 is one of the heaviest-electron systems known to date. Here we used high-resolution neutron spectroscopy to observe low-energy magnetic scattering from a single crystal of this compound in the paramagnetic state. We investigated its temperature dependence and distribution in momentum space, which was not accessible in earlier measurements on polycrystalline samples. At low temperatures, a quasielastic magnetic response with a half-width Gamma approximate to 0.1 meV persists with varying intensity all over the Brillouin zone. It forms a broad hump centered at the (111) scattering vector, surrounded by minima of intensity at (002), (220), and equivalent wave vectors. The momentum-space structure distinguishes this signal from a simple crystal-field excitation at 0.31 meV, suggested previously, and rather lets us ascribe it to short-range dynamical correlations between the neighboring Ce ions, mediated by the itinerant heavy f electrons via the Ruderman-Kittel-Kasuya-Yosida mechanism. With increasing temperature, the energy width of the signal follows the conventional T-1/2 law, Gamma(T) = Gamma(0) + A root T. The momentum-space symmetry of the quasielastic response suggests that it stems from the simple-cubic Ce sublattice occupying the 8c Wyckoff site, whereas the crystallographically inequivalent 4a site remains magnetically silent in this material.
|
|
