40 research outputs found

    Quantification and mitigation of the impacts of extreme weather on power system resilience and reliability

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    Modelling the impact of extreme weather on power systems is a computationally expensive, challenging area of study due to the diversity of threats, complicatedness of modelling, and data and simulation requirements to perform the relevant studies. The impacts of extreme weather – specifically wind – are considered. Factors such as the distribution of outage probability on lines and the potential correlation with wind power generation during storms are investigated; so too is sensitivity of security assessments involving extreme wind to the relationships used between failures and the natural hazard being studied, specifically wind speed. A large scale simulation ensemble is developed and demonstrated to investigate what are deemed the most significant features of power system simulation during extreme weather events. The challenges associated with modelling high impact low probability (HILP) events are studied and demonstrate that the results of security assessments are significantly affected by the granularity of incident weather data being used and the corrections or interpolation being applied to the source data. A generalizable simulation framework is formulated and deployed to investigate the significance of the relationship between incident natural hazards, in this case wind, and its corresponding impact on system resilience. Based on this, a large-scale simulation model is developed and demonstrated to take consideration of a wide variety of factors which can affect power systems during extreme weather events including, but not limited to, under frequency load shedding, line overloads, and high wind speed shutdown and its impact on wind generation. A methodology for quantifying and visualising distributed overhead line failure risk is also demonstrated in tandem with straightforward methods for making wind power projections over transmission systems for security studies. The potential correlation between overhead line risk and wind power generation risk is illustrated visually on representations of GB power networks based on real world data.Open Acces

    Quantification and visualisation of extreme wind effects on transmission network outage probability and wind generation output

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    An approach is demonstrated to visualise overhead line failure rates and estimated wind power output during extreme wind events on transmission networks. Reanalysis data is combined with network data and line failure models to illustrate spatially resolved line failure probability with data corrected for asset altitude and exposure. Wind output is estimated using a corrected power curve to account for high speed shutdown with wind speed corrected for altitude. Case studies demonstrate these methods’ application on representations of real networks of different scales. The proposed methods allow users to determine at-risk regions of overhead line networks and to estimate the impact on wind power output. Such techniques could equally be applied to forecasted weather conditions to aid in resilience planning. The methods are shown to be particularly sensitive to the weather data used, especially when modelling risk on overhead lines, but are still shown to be useful as an indicative representation of system risk. The techniques also provide a more robust method of representing weather-related failure rates on lines considerate of the altitude, voltage level, and their varying exposure to weather conditions than current techniques typically provide, which can be used to usefully represent failure probability of lines during storms

    Tissue-Specific Increases in 11β-Hydroxysteroid Dehydrogenase Type 1 in Normal Weight Postmenopausal Women

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    With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11βHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11βHSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11βHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5α-tetrahydrocortisol+5β-tetrahydrocortisol)/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05), indicating an increased whole-body 11βHSD1 activity. Postmenopausal women had higher 11βHSD1 gene expression in subcutaneous fat (P<0.05). Hepatic first pass conversion of oral cortisone to cortisol was also increased in postmenopausal women versus premenopausal women in follicular phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion), suggesting higher hepatic 11βHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11βHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women

    The emergence of team resilience: A multilevel conceptual model of facilitating factors

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    With empirical research on team resilience on the rise, there is a need for an integrative conceptual model that delineates the essential elements of this concept and offers a heuristic for the integration of findings across studies. To address this need, we propose a multilevel model of team resilience that originates in the resources of individual team members and emerges as a team-level construct through dynamic person–situation interactions that are triggered by adverse events. In so doing, we define team resilience as an emergent outcome characterized by the trajectory of a team's functioning, following adversity exposure, as one that is largely unaffected or returns to normal levels after some degree of deterioration in functioning. This conceptual model offers a departure point for future work on team resilience and reinforces the need to incorporate inputs and process mechanisms inherent within dynamic interactions among individual members of a team. Of particular, importance is the examination of these inputs, process mechanisms and emergent states, and outcomes over time, and in the context of task demands, objectives, and adverse events. Practitioner points: Team resilience as a dynamic, multilevel phenomenon requires clarity on the individual- and team-level factors that foster its emergence within occupational and organizational settings. An understanding of the nature (e.g., timing, chronicity) of adverse events is key to studying and intervening to foster team resilience within occupational and organizational settings

    A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma

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    <p>Abstract</p> <p>Background</p> <p>The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC.</p> <p>Methods/Design</p> <p>The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 2<sup>1/2</sup> -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating.</p> <p>Discussion</p> <p>If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC.</p> <p>Trial Register</p> <p>Trial registered at <url>http://www.clinicaltrials.gov</url>: NCT00355862</p> <p>(EudraCT Number: 2005-005362-36)</p

    Dissociated control as a signature of typological variability in high hypnotic suggestibility

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    This study tested the prediction that dissociative tendencies modulate the impact of a hypnotic induction on cognitive control in different subtypes of highly suggestible individuals. Low suggestible (LS), low dissociative highly suggestible (LDHS), and high dissociative highly suggestible (HDHS) participants completed the Stroop colornaming task in control and hypnosis conditions. The magnitude of conflict adaptation (faster response times on incongruent trials preceded by an incongruent than those preceded by a congruent trial) was used as a measure of cognitive control. LS and LDHS participants displayed marginally superior up-regulation of cognitive control following a hypnotic induction, whereas HDHS participants’ performance declined. These findings indicate that dissociative tendencies modulate the influence of a hypnotic induction on cognitive control in high hypnotic suggestibility and suggest that HS individuals are comprised of distinct subtypes with dissimilar cognitive profiles

    A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma

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    Peer reviewe

    Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma : A Randomized, Multicenter, Open-Label Phase 3 Trial

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    Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Results Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age 60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Conclusions Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.Peer reviewe

    Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

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    Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

    Digital twin-based real-time assessment of resilience in microgrids

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    This paper presents a Digital Twin (DT)-based methodology for real-time assessment of microgrid resilience. Unlike conventional assessment methods, the proposed approach makes use of live system data via the DT of a microgrid; considers not only the steady-state power/energy balancing, but also the dynamic system security constraints under adverse operational conditions associated with line or generator outages. A real-time model based on the future anticipated microgrid at the University of Strathclyde campus has been developed in the RTDS simulator, and a prototype DT of the microgrid and the proposed DT-based resilience assessment have been implemented on a hardware platform, which is interfaced with the RTDS via communication links for realistic demonstration. Preliminary results are generated to illustrate the fundamental concepts of the approach, where N-1 tests and a large sample size are used to generate visualisations of system risk and impact of different events to identify high risk components and compute performance metrics e.g. loss of load probability. This work is intended to be continued on larger networks with more complex systems to demonstrate the value of fast-acting resilience quantification
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