5,760 research outputs found

    A very brief introduction to quantum computing and quantum information theory for mathematicians

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    This is a very brief introduction to quantum computing and quantum information theory, primarily aimed at geometers. Beyond basic definitions and examples, I emphasize aspects of interest to geometers, especially connections with asymptotic representation theory. Proofs of most statements can be found in standard references

    Predicting CD4 T-cell reconstitution following paediatric haematopoietic stem cell transplantation.

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    Haematopoietic stem cell transplantation is an increasingly common treatment for children with a range of haematological disorders. Conditioning with cytotoxic chemotherapy and total body irradiation leaves patients severely immunocompromised. T-cell reconstitution can take several years due to delayed restoration of thymic output. Understanding T-cell reconstitution in children is complicated by normal immune system maturation, heterogeneous diagnoses, and sparse uneven sampling due to the long time spans involved. We describe here a mechanistic mathematical model for CD4 T-cell immune reconstitution following pediatric transplantation. Including relevant biology and using mixed-effects modelling allowed the factors affecting reconstitution to be identified. Bayesian predictions for the long-term reconstitution trajectories of individual children were then obtained using early post-transplant data. The model was developed using data from 288 children; its predictive ability validated on data from a further 75 children, with long-term reconstitution predicted accurately in 81% of patients. This article is protected by copyright. All rights reserved

    Revising Pediatric Vancomycin Dosing Accounting for Nephrotoxicity in a Pharmacokinetic-Pharmacodynamic Model

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    This study aimed to suggest an initial pediatric vancomycin dose regimen through population pharmacokinetic-pharmacodynamic modeling. A population pharmacokinetic approach was used to analyze vancomycin concentration-time data from a large pediatric cohort. Pharmacokinetic target attainment for patients with bloodstream isolates was compared with clinical outcome using logistic regression and classification and regression trees. Change in serum creatinine during treatment was used as an indicator of acute nephrotoxicity. Probability of acute kidney injury (50% increase from baseline) or kidney failure (75% increase from baseline) was evaluated using logistic regression. An initial dosing regimen was derived, personalized by age, weight, and serum creatinine, using stochastic simulations. Data from 785 hospitalized pediatric patients (1 day to 21 years of age) with suspected Gram-positive infections were collected. Estimated (relative standard error) typical clearance, volume of distribution 1, intercompartmental clearance, and volume of distribution 2 were (standardized to 70 kg) 4.84 (2.38) liters/h, 39.9 (8.15) liters, 3.85 (17.3) liters/h, and 37.8 (10.2) liters, respectively. While cumulative vancomycin exposure correlated positively with the development of nephrotoxicity (713 patients), no clear relationship between vancomycin area under the plasma concentration-time curve and efficacy was found (102 patients). Predicted probability of acute kidney injury and kidney failure with the optimized dosing regimen at day 5 was 10 to 15% and 5 to 10%, increasing by approximately 50% on day 7 and roughly 100% on day 10 across all age groups. This study presents the first data-driven pediatric dose selection to date accounting for nephrotoxicity, and it indicates that cumulative vancomycin exposure best describes risk of acute kidney injury and acute kidney failure

    A new technique for transumbilical insertion of central venous silicone catheters in newborn infants

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    Aim: A new technique allowing placement of umbilical silicone venous catheters (USVC) is described and compared with percutaneous silicone venous catheters (PSVC)

    An Optimization Approach to the Ordering Phase of an Attended Home Delivery Service

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    Attended Home Delivery (AHD) systems are used whenever a supplying company offers online shopping services that require that customers must be present when their deliveries arrive. Therefore, the supplying company and the customer must both agree on a time window, which ideally is rather short, during which delivery is guaranteed. Typically, a capacitated Vehicle Routing Problem with Time Windows forms the underlying optimization problem of the AHD system. In this work, we consider an AHD system that runs the online grocery shopping service of an international grocery retailer. The ordering phase, during which customers place their orders through the web service, is the computationally most challenging part of the AHD system. The delivery schedule must be built dynamically as new orders are placed. We propose a solution approach that allows to (non-stochastically) determine which delivery time windows can be offered to potential customers. We split the computations of the ordering phase into four key steps. For performing these basic steps we suggest both a heuristic approach and a hybrid approach employing mixed-integer linear programs. In an experimental evaluation we demonstrate the efficiency of our approaches

    Development and evaluation of a gentamicin pharmacokinetic model that facilitates opportunistic gentamicin therapeutic drug monitoring in neonates and infants.

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    Trough gentamicin therapeutic drug monitoring (TDM) is time-consuming, disruptive to neonatal clinical care and a patient safety issue. Bayesian models could allow TDM to be performed opportunistically at the time of routine blood tests. This study aimed to develop and prospectively evaluate a new gentamicin model and a novel Bayesian computer tool (neoGent) for TDM use in neonatal intensive care. We also evaluated model performance for predicting peak concentrations and AUC(0-t). A pharmacokinetic meta-analysis was performed on pooled data from three studies (1325 concentrations from 205 patients). A 3-compartment model was used with covariates being: allometric weight scaling, postmenstrual and postnatal age, and serum creatinine. Final parameter estimates (standard error) were: clearance: 6.2 (0.3) L/h/70kg; central volume (V) 26.5 (0.6) L/70kg; inter-compartmental disposition: Q=2.2 (0.3) L/h/70kg, V2=21.2 (1.5) L/70kg, Q2=0.3 (0.05) L/h/70kg, V3=148 (52.0) L/70kg. The model's ability to predict trough concentrations from an opportunistic sample was evaluated in a prospective observational cohort study that included data from 163 patients with 483 concentrations collected in five hospitals. Unbiased trough predictions were obtained: median (95% confidence interval (CI)) prediction error was 0.0004 (-1.07, 0.84) mg/L. Results also showed peaks and AUC(0-t) could be predicted (from one randomly selected sample) with little bias but relative imprecision with median (95% CI) prediction error being 0.16 (-4.76, 5.01) mg/L and 10.8 (-24.9, 62.2) mg h/L, respectively. NeoGent was implemented in R/NONMEM, and in the freely available TDMx software

    Iatrogenic Subtotal Stenosis of the Right Subclavian Artery Treated With Percutaneous Transluminal Angioplasty

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    This report describes a rare vascular complication of surgical placement of a marking clip and a possible approach to problem solving. A 55-year-old patient presented with loss of sensation in the fingers and loss of peripheral pulsations in the right arm 4 days after right upper lobectomy for a pT2N1 moderately differentiated adenocarcinoma of the lung. Duplex examination and computed tomography were performed the same day and showed a subtotal stenosis of the right subclavian artery, which was caused by the surgical placement of a metal clip to mark the surgical boundary. Selective angiography was subsequently performed. Percutaneous transluminal angioplasty (PTA) successfully dilated the stenosis and pushed the clip off. Flow in the right subclavian artery (RSA) was completely restored as were neurology and peripheral pulses. In conclusion, arterial stenosis by a surgical (marking) clip may be feasibly treated with PTA
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