Nonlinear Normalization in Limit Theorems for Extremes

2000 Mathematics Subject Classification: 60G70, 60F05.It is well known that under linear normalization the maxima of iid random variables converges in distribution to one of the three types of max-stable laws: Frechet, Gumbel and Weibull. During the last two decades the first author and her collaborators worked out a limit theory for extremes and extremal processes under non-linear but monotone normalizing mappings. In this model there is only one type of max-stable distributions and all continuous and strictly increasing df's belong to it. In a recent paper on General max-stable laws, Sreehari points out two "confusing" results in Pancheva (1984). They concern the explicit form of a max-stable df with respect to a continuous one-parameter group of max-automorphisms, and domain of attraction conditions. In the present paper the first claim is answered by a detailed explanation of the explicit form, while for the second we give a revised proof. The rate of convergence is also discussed

An Estimate of the Probability Pr(X<Y)

2000 Mathematics Subject Classification: 33C90, 62E99In the area of stress-strength models there has been a large amount of work as regards estimation of the probability R = Pr(X<Y) when X and Y are independent random variables belonging to the same univariate family of distributions. In this paper we propose an estimate of this quantity based on a simple property of the uniform distribution. We illustrate the use of the estimate with bootstrap confidence intervals for four commonly known distributions (normal, exponential, gamma and beta).The third author is supported by by NFSI-Bulgaria, Grant No. MM-1101/2001

Glucose-stimulated insulin response in pregnant sheep following acute suppression of plasma non-esterified fatty acid concentrations

BACKGROUND: Elevated non-esterified fatty acids (NEFA) concentrations in non-pregnant animals have been reported to decrease pancreatic responsiveness. As ovine gestation advances, maternal insulin concentrations fall and NEFA concentrations increase. Experiments were designed to examine if the pregnancy-associated rise in NEFA concentration is associated with a reduced pancreatic sensitivity to glucose in vivo. We investigated the possible relationship of NEFA concentrations in regulating maternal insulin concentrations during ovine pregnancy at three physiological states, non-pregnant, non-lactating (NPNL), 105 and 135 days gestational age (dGA, term 147+/- 3 days). METHODS: The plasma concentrations of insulin, growth hormone (GH) and ovine placental lactogen (oPL) were determined by double antibody radioimmunoassay. Insulin responsiveness to glucose was measured using bolus injection and hyperglycaemic clamp techniques in 15 non-pregnant, non-lactating ewes and in nine pregnant ewes at 105 dGA and near term at 135 dGA. Plasma samples were also collected for hormone determination. In addition to bolus injection glucose and insulin Area Under Curve calculations, the Mean Plasma Glucose Increment, Glucose Infusion Rate and Mean Plasma Insulin Increment and Area Under Curve were determined for the hyperglycaemic clamp procedures. Statistical analysis of data was conducted with Students t-tests, repeated measures ANOVA and 2-way ANOVA. RESULTS: Maternal growth hormone, placental lactogen and NEFA concentrations increased, while basal glucose and insulin concentrations declined with advancing gestation. At 135 dGA following bolus glucose injections, peak insulin concentrations and insulin area under curve (AUC) profiles were significantly reduced in pregnant ewes compared with NPNL control ewes (p < 0.001 and P < 0.001, respectively). In hyperglycaemic clamp studies, while maintaining glucose levels not different from NPNL ewes, pregnant ewes displayed significantly reduced insulin responses and a maintained depressed insulin secretion. In NPNL ewes, 105 and 135 dGA ewes, the Glucose Infusion Rate (GIR) was constant at approximately 5.8 mg glucose/kg/min during the last 40 minutes of the hyperglycaemic clamp and the Mean Plasma Insulin Increment (MPII) was only significantly (p < 0.001) greater in NPNL ewes. Following the clamp, NEFA concentrations were reduced by approximately 60% of pre-clamp levels in all groups, though a blunted and suppressed insulin response was maintained in 105 and 135 dGA ewes. CONCLUSIONS: Results suggest that despite an acute suppression of circulating NEFA concentrations during pregnancy, the associated steroids and hormones of pregnancy and possibly NEFA metabolism, may act to maintain a reduced insulin output, thereby sparing glucose for non-insulin dependent placental uptake and ultimately, fetal requirements

A Novel Splice-Site Mutation in VEGFC Is Associated with Congenital Primary Lymphoedema of Gordon.

Lymphedema is characterized by chronic swelling of any body part caused by malfunctioning or obstruction in the lymphatic system. Primary lymphedema is often considered genetic in origin. VEGFC, which is a gene encoding the ligand for the vascular endothelial growth factor receptor 3 (VEGFR3/FLT4) and important for lymph vessel development during lymphangiogenesis, has been associated with a specific subtype of primary lymphedema. Through Sanger sequencing of a proband with bilateral congenital pedal edema resembling Milroy disease, we identified a novel mutation (NM_005429.2; c.361+5G>A) in VEGFC. The mutation induced skipping of exon 2 of VEGFC resulting in a frameshift and the introduction of a premature stop codon (p.Ala50ValfsTer18). The mutation leads to a loss of the entire VEGF-homology domain and the C-terminus. Expression of this Vegfc variant in the zebrafish floorplate showed that the splice-site variant significantly reduces the biological activity of the protein. Our findings confirm that the splice-site variant, c.361+5G>A, causes the primary lymphedema phenotype in the proband. We examine the mutations and clinical phenotypes of the previously reported cases to review the current knowledge in this area

Incorporating risk in field services operational planning process

© Springer Nature Switzerland AG 2018. This paper presents a model for the risk minimisation objective in the Stochastic Vehicle Routing Problem (SVRP). In the studied variant of SVRP, service times and travel times are subject to stochastic events, and a time window is constraining the start time for service task. Required skill levels and task priorities increase the complexity of this problem. Most previous research uses a chance-constrained approach to the problem and their objectives are related to traditional routing costs whilst a different approach was taken in this paper. The risk of missing a task is defined as the probability that the technician assigned to the task arrives at the customer site later than the time window. The problem studied in this paper is to generate a schedule that minimises the maximum of risks and sum of risks over all the tasks considering the effect of skill levels and task priorities. The stochastic duration of each task is supposed to follow a known normal distribution. However, the distribution of the start time of the service at a customer site will not be normally distributed due to time window constraints. A method is proposed and tested to approximate the start time distribution as normal. Moreover, a linear model can be obtained assuming identical variance of task durations. Additionally Simulated Annealing method was applied to solve the problem. Results of this work have been applied to an industrial case of SVRP where field engineering individuals drive to customer sites to provide time-constrained services. This original approach gives a robust schedule and allows organisations to pay more attention to increasing customer satisfaction and become more competitive in the market

The collateral damage of COVID-19 to cardiovascular services. A meta-Analysis

Aims: The effect of the COVID-19 pandemic on care and outcomes across non-COVID-19 cardiovascular (CV) diseases is unknown. A systematic review and meta-Analysis was performed to quantify the effect and investigate for variation by CV disease, geographic region, country income classification and the time course of the pandemic. Methods and results: From January 2019 to December 2021, Medline and Embase databases were searched for observational studies comparing a pandemic and pre-pandemic period with relation to CV disease hospitalisations, diagnostic and interventional procedures, outpatient consultations, and mortality. Observational data were synthesised by incidence rate ratios (IRR) and risk ratios (RR) for binary outcomes and weighted mean differences for continuous outcomes with 95% confidence intervals. The study was registered with PROSPERO (CRD42021265930). A total of 158 studies, covering 49 countries and 6 continents, were used for quantitative synthesis. Most studies (80%) reported information for high-income countries (HICs). Across all CV disease and geographies there were fewer hospitalisations, diagnostic and interventional procedures, and outpatient consultations during the pandemic. By meta-regression, in low-middle income countries (LMICs) compared to HICs the decline in ST-segment elevation myocardial infarction (STEMI) hospitalisations (RR 0.79, 95% confidence interval [CI] 0.66-0.94) and revascularisation (RR 0.73, 95% CI 0.62-0.87) was more severe. In LMICs, but not HICs, in-hospital mortality increased for STEMI (RR 1.22, 95% CI 1.10-1.37) and heart failure (RR 1.08, 95% CI 1.04-1.12). The magnitude of decline in hospitalisations for CV diseases did not differ between the first and second wave. Conclusions: There was substantial global collateral CV damage during the COVID-19 pandemic with disparity in severity by country income classification