| 1. |
- Mueller, Sven Christian, et al.
(författare)
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Interfacing Power System and ICT Simulators : Challenges, State-of-the-Art, and Case Studies
- 2018
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Ingår i: IEEE Transactions on Smart Grid. - : Institute of Electrical and Electronics Engineers (IEEE). - 1949-3053 .- 1949-3061. ; 9:1, s. 14-24
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Tidskriftsartikel (refereegranskat)abstract
- With the transition toward a smart grid, the power system has become strongly intertwined with the information and communication technology (ICT) infrastructure. The interdependency of both domains requires a combined analysis of physical and ICT processes, but simulating these together is a major challenge due to the fundamentally different modeling and simulation concepts. After outlining these challenges, such as time synchronization and event handling, this paper presents an overview of state-of-the-art solutions to interface power system and ICT simulators. Due to their prominence in recent research, a special focus is set on co-simulation approaches and their challenges and potentials. Further, two case studies analyzing the impact of ICT on applications in power system operation illustrate the necessity of a holistic approach and show the capabilities of state-of-the-art co-simulation platforms.
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| 2. |
- Albert, Christian, et al.
(författare)
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Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy : A Systematic Review and Meta-analysis
- 2020
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Ingår i: American Journal of Kidney Diseases. - : Elsevier BV. - 0272-6386 .- 1523-6838. ; 76:6, s. 826-
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Forskningsöversikt (refereegranskat)abstract
- Rationale & Objective: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction.Study Design: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.Setting & Study Populations: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms.Selection Criteria for Studies: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI.Data Extraction: Individual-study-data meta analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis.Analytical Approach: Individual-study-data meta analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses.Results: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.790.81) and 0.86 (95% CI, 0.84-0.8 6). Cutoff concentrations at 95% specificity for urinary NGAL were >580 ng/mL with 27% sensitivity for severe AKI and >589 ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were >364 ng/mL with 44% sensitivity and >546 ng/mL with 26% sensitivity, respectively.Limitations: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies. Conclusions: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.
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| 3. |
- George, Julie, et al.
(författare)
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Comprehensive genomic profiles of small cell lung cancer
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
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Tidskriftsartikel (refereegranskat)abstract
- We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
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| 4. |
- Gualandro, Danielle M. M., et al.
(författare)
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Acute heart failure after non-cardiac surgery: incidence, phenotypes, determinants and outcomes
- 2023
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 25:3, s. 347-357
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Tidskriftsartikel (refereegranskat)abstract
- Aims Primary acute heart failure (AHF) is a common cause of hospitalization. AHF may also develop postoperatively (pAHF). The aim of this study was to assess the incidence, phenotypes, determinants and outcomes of pAHF following non-cardiac surgery.Methods and results A total of 9164 consecutive high-risk patients undergoing 11 262 non-cardiac inpatient surgeries were prospectively included. The incidence, phenotypes, determinants and outcome of pAHF, centrally adjudicated by independent cardiologists, were determined. The incidence of pAHF was 2.5% (95% confidence interval [CI] 2.2-2.8%); 51% of pAHF occurred in patients without known heart failure (de novo pAHF), and 49% in patients with chronic heart failure. Among patients with chronic heart failure, 10% developed pAHF, and among patients without a history of heart failure, 1.5% developed pAHF. Chronic heart failure, diabetes, urgent/emergent surgery, atrial fibrillation, cardiac troponin elevations above the 99th percentile, chronic obstructive pulmonary disease, anaemia, peripheral artery disease, coronary artery disease, and age, were independent predictors of pAHF in the logistic regression model. Patients with pAHF had significantly higher all-cause mortality (44% vs. 11%, p < 0.001) and AHF readmission (15% vs. 2%, p < 0.001) within 1 year than patients without pAHF. After Cox regression analysis, pAHF was an independent predictor of all-cause mortality (adjusted hazard ratio [aHR] 1.7 [95% CI 1.3-2.2]; p < 0.001) and AHF readmission (aHR 2.3 [95% CI 1.5-3.7]; p < 0.001). Findings were confirmed in an external validation cohort using a prospective multicentre cohort of 1250 patients (incidence of pAHF 2.4% [95% CI 1.6-3.3%]).Conclusions Postoperative AHF frequently developed following non-cardiac surgery, being de novo in half of cases, and associated with a very high mortality.
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| 5. |
- Koettgen, Anna, et al.
(författare)
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Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:2, s. 145-154
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Tidskriftsartikel (refereegranskat)abstract
- Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
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| 6. |
- Rydén, Lars, et al.
(författare)
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ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:39, s. 3035-3087
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Tidskriftsartikel (refereegranskat)abstract
- This is the second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions. The growing awareness of the strong biological relationship between DM and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007. Some assert that too many guidelines are being produced but, in this burgeoning field, five years in the development of both basic and clinical science is a long time and major trials have reported in this period, making it necessary to update the previous Guidelines.
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| 7. |
- Boeddinghaus, Jasper, et al.
(författare)
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Impact of age on the performance of the ESC 0/1h-algorithms for early diagnosis of myocardial infarction
- 2018
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Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 39:42, s. 3780-3794
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Tidskriftsartikel (refereegranskat)abstract
- Aims We aimed to evaluate the impact of age on the performance of the European Society of Cardiology (ESC) 0/1h-algorithms and to derive and externally validate alternative cut-offs specific to older patients. Methods and results We prospectively enrolled patients presenting to the emergency department (ED) with symptoms suggestive of and results acute myocardial infarction in three large diagnostic studies. Final diagnoses were adjudicated by two independent cardiologists. High-sensitivity cardiac troponin (hs-cTn) T and I concentrations were measured at presentation and after 1 h. Patients were stratified according to age [<55 years (young), >= 55 to <70 years (middle-age), >= 70 years (old)]. Rule-out safety of the ESC hs-cTnT 0/1h-algorithm was very high in all age-strata: sensitivity 100% [95% confidence interval (95% CI) 94.9-100] in young, 99.3% (95% CI 96.0-99.9) in middle-age, and 99.3% (95% CI 97.599.8) in old patients. Accuracy of rule-in decreased with age: specificity 97.0% (95% CI 95.8-97.9) in young, 96.1% (95% CI 94.5-97.2) in middle-age, and 92.7% (95% CI 90.7-94.3) in older patients. Triage efficacy decreased with increasing age (young 93%, middle-age 80%, old 55%, P <0.001). Similar results were found for the ESC hs-cTnT 0/1h-algorithm. Alternative, slightly higher cut-off concentrations optimized for older patients maintained very high safety of rule-out, increased specificity of rule-in (P< 0.01), reduced overall efficacy for hs-cTnT (P <0.01), while maintaining efficacy for hs-cTnl. Findings were confirmed in two validation cohorts (n = 2767). Conclusion While safety of the ESC 0/1h-algorithms remained very high, increasing age significantly reduced overall efficacy and the accuracy of rule-in. Alternative slightly higher cut-off concentrations may be considered for older patients, particularly if using hs-cTnl.
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| 8. |
- Chew, Michelle S., et al.
(författare)
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Identification of myocardial injury using perioperative troponin surveillance in major noncardiac surgery and net benefit over the Revised Cardiac Risk Index
- 2022
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Ingår i: British Journal of Anaesthesia. - : Elsevier. - 0007-0912 .- 1471-6771. ; 128:1, s. 26-36
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with perioperative myocardial injury are at risk of death and major adverse cardiovascular and cerebrovascular events (MACCE). The primary aim of this study was to determine optimal thresholds of preoperative and perioperative changes in high-sensitivity cardiac troponin T (hs-cTnT) to predict MACCE and mortality.METHODS: Prospective, observational, cohort study in patients ≥50 yr of age undergoing elective major noncardiac surgery at seven hospitals in Sweden. The exposures were hs-cTnT measured before and days 0-3 after surgery. Two previously published thresholds for myocardial injury and two thresholds identified using receiver operating characteristic analyses were evaluated using multivariable logistic regression models and externally validated. The weighted comparison net benefit method was applied to determine the additional value of hs-cTnT thresholds when compared with the Revised Cardiac Risk Index (RCRI). The primary outcome was a composite of 30-day all-cause mortality and MACCE.RESULTS: We included 1291 patients between April 2017 and December 2020. The primary outcome occurred in 124 patients (9.6%). Perioperative increase in hs-cTnT ≥14 ng L-1 above preoperative values provided statistically optimal model performance and was associated with the highest risk for the primary outcome (adjusted odds ratio 2.9, 95% confidence interval 1.8-4.7). Validation in an independent, external cohort confirmed these findings. A net benefit over RCRI was demonstrated across a range of clinical thresholds.CONCLUSIONS: Perioperative increases in hsTnT ≥14 ng L-1 above baseline values identifies acute perioperative myocardial injury and provides a net prognostic benefit when added to RCRI for the identification of patients at high risk of death and MACCE.CLINICAL TRIAL REGISTRATION: NCT03436238.
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| 9. |
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| 10. |
- Meister, Rebecca, et al.
(författare)
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Prediction of perioperative myocardial infarction/injury in high-risk patients after noncardiac surgery
- 2023
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Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 2048-8726 .- 2048-8734. ; 12:11, s. 729-739
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Tidskriftsartikel (refereegranskat)abstract
- Aims Perioperative myocardial infarction/injury (PMI) is a surprisingly common yet difficult-to-predict cardiac complication in patients undergoing noncardiac surgery. We aimed to assess the incremental value of preoperative cardiac troponin (cTn) concentration in the prediction of PMI. Methods and results Among prospectively recruited patients at high cardiovascular risk (age >= 65 years or >= 45 years with preexisting cardiovascular disease), PMI was defined as an absolute increase in high-sensitivity cTnT (hs-cTnT) concentration of >= 14 ng/L (the 99th percentile) above the preoperative concentration. Perioperative myocardial infarction/injury was centrally adjudicated by two independent cardiologists using serial measurements of hs-cTnT. Using logistic regression, three models were derived: Model 1 including patient- and procedure-related information, Model 2 adding routinely available laboratory values, and Model 3 further adding preoperative hs-cTnT concentration. Models were also compared vs. preoperative hs-cTnT alone. The findings were validated in two independent cohorts. Among 6944 patients, PMI occurred in 1058 patients (15.2%). The predictive accuracy as quantified by the area under the receiver operating characteristic curve was 0.73 [95% confidence interval (CI) 0.71-0.74] for Model 1, 0.75 (95% CI 0.74-0.77) for Model 2, 0.79 (95% CI 0.77-0.80) for Model 3, and 0.74 for hs-cTnT alone. Model 3 included 10 preoperative variables: age, body mass index, known coronary artery disease, metabolic equivalent >4, risk of surgery, emergency surgery, planned duration of surgery, haemoglobin, platelet count, and hs-cTnT. These findings were confirmed in both independent validation cohorts (n = 722 and n = 966). Conclusion Preoperative cTn adds incremental value above patient- and procedure-related variables as well as routine laboratory variables in the prediction of PMI.
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