On the numerical solution of Kronecker-based infinite level-dependent QBD processes

Cataloged from PDF version of article.Infinite level-dependent quasi-birth-and-death (LDQBD) processes can be used to model Markovian systems with countably infinite multidimensional state spaces. Recently it has been shown that sums of Kronecker products can be used to represent the nonzero blocks of the transition rate matrix underlying an LDQBD process for models from stochastic chemical kinetics. This paper extends the form of the transition rates used recently so that a larger class of models including those of call centers can be analyzed for their steady-state. The challenge in the matrix analytic solution then is to compute conditional expected sojourn time matrices of the LDQBD model under low memory and time requirements after truncating its countably infinite state space judiciously. Results of numerical experiments are presented using a Kronecker-based matrix-analytic solution on models with two or more countably infinite dimensions and rules of thumb regarding better implementations are derived. In doing this, a more recent approach that reduces memory requirements further by enabling the computation of steady-state expectations without having to obtain the steady-state distribution is also considered. (C) 2013 Elsevier B.V. All rights reserved

Burden, duration and costs of hospital bed closures due to acute gastroenteritis in England per winter, 2010/11-2015/16.

BACKGROUND: Bed closures due to acute gastroenteritis put hospitals under pressure each winter. In England, the National Health Service (NHS) has monitored the winter situation for all acute trusts since 2010/11. AIM: To estimate the burden, duration and costs of hospital bed closures due to acute gastroenteritis in winter. METHODS: A retrospective analysis of routinely collected time-series data of bed closures due to diarrhoea and vomiting was conducted for the winters 2010/11 to 2015/16. Two key issues were addressed by imputing non-randomly missing values at provider level, and filtering observations to a range of dates recorded in all six winters. The lowest and highest values imputed were taken to represent the best- and worst-case scenarios. Bed-days were costed using NHS reference costs, and potential staff absence costs were based on previous studies. FINDINGS: In the best-to-worst case, a median of 88,000-113,000 beds were closed due to gastroenteritis each winter. Of these, 19.6-20.4% were unoccupied. On average, 80% of providers were affected, and had closed beds for a median of 15-21 days each winter. Hospital costs of closed beds were £5.7-£7.5 million, which increased to £6.9-£10.0 million when including staff absence costs due to illness. CONCLUSIONS: The median number of hospital beds closed due to acute gastroenteritis per winter was equivalent to all general and acute hospital beds in England being unavailable for a median of 0.88-1.12 days. Costs for hospitals are high but vary with closures each winter

Should NICE reconsider the 2016 UK guidelines on TB contact tracing? A cost-effectiveness analysis of contact investigations in London.

BACKGROUND: In January 2016, clinical TB guidance in the UK changed to no longer recommend screening contacts of non-pulmonary, non-laryngeal (ETB) index cases. However, no new evidence was cited for this change, and there is evidence that screening these contacts may be worthwhile. The objective of this study was to estimate the cost-effectiveness of screening contacts of adult ETB cases and adult pulmonary or laryngeal TB (PTB) cases in London, UK. METHODS: We carried out a cross-sectional analysis of data collected on TB index cases and contacts in the London TB register and an economic evaluation using a static model describing contact tracing outcomes. Incremental cost-effectiveness ratios (ICERs) were calculated using no screening as the baseline comparator. All adult TB cases (≥15 years old) in London from 2012 to 2015, and their contacts, were eligible (2465/5084 PTB and 2559/6090 ETB index cases were included). RESULTS: Assuming each contact with PTB infects one person/month, the ICER of screening contacts of ETB cases was £78 000/quality-adjusted life-years (QALY) (95% CI 39 000 to 140 000), and screening contacts of PTB cases was £30 000/QALY (95% CI 18 000 to 50 000). The ICER of screening contacts of ETB cases was £30 000/QALY if each contact with PTB infects 3.4 people/month. Limitations of this study include the use of self-reported symptomatic periods and lack of knowledge about onward transmission from PTB contacts. CONCLUSIONS: Screening contacts of ETB cases in London was almost certainly not cost-effective at any conventional willingness-to-pay threshold in England, supporting recent changes to National Institute for Health and Care Excellence national guidelines

Metabolic engineering of astaxanthin biosynthesis in maize endosperm and characterization of a prototype high oil hybrid

Maize was genetically engineered for the biosynthesis of the high value carotenoid astaxanthin in the kernel endosperm. Introduction of a β-carotene hydroxylase and a β-carotene ketolase into a white maize genetic background extended the carotenoid pathway to astaxanthin. Simultaneously, phytoene synthase, the controlling enzyme of carotenogenesis, was over-expressed for enhanced carotenoid production and lycopene ε-cyclase was knocked-down to direct more precursors into the β-branch of the extended ketocarotenoid pathway which ends with astaxanthin. This astaxanthin-accumulating transgenic line was crossed into a high oil- maize genotype in order to increase the storage capacity for lipophilic astaxanthin. The high oil astaxanthin hybrid was compared to its astaxanthin producing parent. We report an in depth metabolomic and proteomic analysis which revealed major up- or down- regulation of genes involved in primary metabolism. Specifically, amino acid biosynthesis and the citric acid cycle which compete with the synthesis or utilization of pyruvate and glyceraldehyde 3-phosphate, the precursors for carotenogenesis, were down-regulated. Nevertheless, principal component analysis demonstrated that this compositional change is within the range of the two wild type parents used to generate the high oil producing astaxanthin hybrid

The distribution of carotenoids in hens fed on biofortified maize is influenced by feed composition, absorption, resource allocation and storage

Carotenoids are important dietary nutrients with health-promoting effects. The biofortification of staple foods with carotenoids provides an efficient delivery strategy but little is known about the fate and distribution of carotenoids supplied in this manner. The chicken provides a good model of human carotenoid metabolism so we supplemented the diets of laying hens using two biofortified maize varieties with distinct carotenoid profiles and compared the fate of the different carotenoids in terms of distribution in the feed, the hen’s livers and the eggs. We found that after a period of depletion, pro-vitamin A (PVA) carotenoids were preferentially diverted to the liver and relatively depleted in the eggs, whereas other carotenoids were transported to the eggs even when the liver remained depleted. When retinol was included in the diet, it accumulated more in the eggs than the livers, whereas PVA carotenoids showed the opposite profile. Our data suggest that a transport nexus from the intestinal lumen to the eggs introduces bottlenecks that cause chemically-distinct classes of carotenoids to be partitioned in different ways. This nexus model will allow us to optimize animal feed and human diets to ensure that the health benefits of carotenoids are delivered in the most effective manner.This research was supported by grants PIM2010PKB-00746 CAROMAIZE, from Ministerio de Economia y Competitividad (MINECO) Spain; RecerCaixa PC084082; and European Research Council IDEAS Proof of Concept Program Multinutrient Maize (to PC)