A process algebra based simulation model of a Diagnostic Radiology Department

In the last years, it's possible to observe a growing interest in applying in the health care sector tools and methods, which have been successfully applied in other service and industry sectors and have helped to improve planning and efficient use of resources, while maintaining high quality of the delivered service or product. Discrete event simulation represents a powerful and proven tool, which enables the experimentation of several possible solutions at relatively low cost. This paper is focused on the modeling and analysis of a Diagnostic Radiology Department (DRD) in an important Southern Italy hospital and adopts a discrete-event simulation approach based on a process algebra dialect, called $. Some "scenario" results are then illustrated in order to derive basic performance indicators of the system, which could be useful to hospital decision-makers and constitute a starting point for a deeper cost-benefit evaluation

Workforce Aging in Production Systems: Modeling and Performance Evaluation

AbstractHuman factor is considered as a cost effective alternative to expensive automated solutions, as well as an easily interchangeable high flexible resource. However, for many years the influence of human behavior on production system performance has been underestimated and a lot of unrealistic assumptions have been used to simplify the human component modeling.Nowadays, population aging is acknowledged as a global trend. Among individual factors impacting on workers’ performance, high attention is being paid to the age from scientific community, policy-makers and business leaders.The aim of this paper is to provide some highlights about the main scientific literature findings, regarding aging effects, in a quickly consultable and synthetic form; the elements characterizing human performance could then be included in models and ergonomic evaluation tools.In the initial part of the paper, demographic aspects and their implications on workforce composition are illustrated; successively, a state of the art of human behavior modeling is provided and main findings on age-related performance characteristics are summarized

The hyperornithinemia-hyperammonemia-homocitrullinuria syndrome

Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive disorder of the urea cycle. HHH has a panethnic distribution, with a major prevalence in Canada, Italy and Japan. Acute clinical signs include intermittent episodes of vomiting, confusion or coma and hepatitis-like attacks. Alternatively, patients show a chronic course with aversion for protein rich foods, developmental delay/intellectual disability, myoclonic seizures, ataxia and pyramidal dysfunction. HHH syndrome is caused by impaired ornithine transport across the inner mitochondrial membrane due to mutations in SLC25A15 gene, which encodes for the mitochondrial ornithine carrier ORC1. The diagnosis relies on clinical signs and the peculiar metabolic triad of hyperammonemia, hyperornithinemia, and urinary excretion of homocitrulline. HHH syndrome enters in the differential diagnosis with other inherited or acquired conditions presenting with hyperammonemia

CUGC for hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome

From 1999 to date, 50 affecting function variants have been identified and associated to HHH syndrome [1–5]. As it is not available in the literature a complete up-to-date list of disease-causing variants for SLC25A15 gene, we included this information as a Supplementary Excel sheet (See Supplementary Material File #1): this list was created by using LOVD and ClinVar databases and liked to the relevant literature reference. Reported variants consist of: 29 missense variants, 4 frameshift, 11 nonsense, 2 splicing, 2 small deletion, 1 in frame insertion, 1 gross deletion

Unravelling new pathways of sterol metabolism

Purpose of reviewTo update researchers of recently discovered metabolites of cholesterol and of its precursors and to suggest relevant metabolic pathways.Recent findingsPatients suffering from inborn errors of sterol biosynthesis, transport and metabolism display unusual metabolic pathways, which may be major routes in the diseased state but minor in the healthy individual. Although quantitatively minor, these pathways may still be important in healthy individuals. Four inborn errors of metabolism, Smith-Lemli-Opitz syndrome, cerebrotendinous xanthomatosis and Niemann Pick disease types B (NPB) and C (NPC) result from mutations in different genes but can generate elevated levels of the same sterol metabolite, 7-oxocholesterol, in plasma. How this molecule is metabolized further is of great interest as its metabolites may have an important role in embryonic development. A second metabolite, abundant in NPC and NPB diseases, cholestane-3β,5α,6β-triol (3β,5α,6β-triol), has recently been shown to be metabolized to the corresponding bile acid, 3β,5α,6β-trihydroxycholanoic acid, providing a diagnostic marker in plasma. The origin of cholestane-3β,5α,6β-triol is likely to be 3β-hydroxycholestan-5,6-epoxide, which can alternatively be metabolized to the tumour suppressor dendrogenin A (DDA). In breast tumours, DDA levels are found to be decreased compared with normal tissues linking sterol metabolism to cancer.SummaryUnusual sterol metabolites and pathways may not only provide markers of disease, but also clues towards cause and treatment

Diagnosis, treatment, and follow-up of a case of Wolman disease with hemophagocytic lymphohistiocytosis

: Wolman Disease (WD) is a severe multi-system metabolic disease due to lysosomal acid lipase (LAL) deficiency. We report on a WD infant who developed an unusual hemophagocytic lymphohistiocytosis (HLH) phenotype related to WD treated with sebelipase alfa. A male baby came to our attention at six months of life for respiratory insufficiency and sepsis, abdominal distension, severe hepatosplenomegaly, diarrhea, and severe growth retardation. HLH was diagnosed and treated with intravenous immunoglobulin, steroids, cyclosporine, broad-spectrum antimicrobial therapy, and finally with the anti-IL-6 drug tocilizumab. WD was suspected for the presence of adrenal calcifications and it was confirmed by LAL enzyme activity and by molecular analysis of LIPA. Plasma oxysterols cholestan-3β,5α,6β-triol (C-triol), and 7-ketocholesterol (7-KC) were markedly increased. Sebelipase alfa was started with progressive amelioration of biochemical and clinical features. The child died from sepsis, 2 months after sebelipase discontinuation requested by parents. Our case shows the importance of an early diagnosis of WD and confirms the difficulty to reach a diagnosis in the HLH phenotype. Sebelipase alpha is an effective treatment for LAL deficiency, also in children affected by WD. Further data are necessary to confirm the utility of measuring plasma c-triol as a biochemical marker of the disease

Gully cut- and- fill cycles as related to agromanagement : a historical curve number simulation in the Tigray Highlands

Gully cut-and-fill dynamics are often thought to be driven by climate and/or deforestation related to population pressure. However, in this case-study of nine representative catchments in the Northern Ethiopian Highlands, we find that neither climate changes nor deforestation can explain gully morphology changes over the twentieth century. Firstly, by using a Monte Carlo simulation to estimate historical catchment-wide curve numbers, we show that the landscape was already heavily degraded in the nineteenth and early twentieth century – a period with low population density. The mean catchment-wide curve number (> 80) one century ago was, under the regional climatic conditions, already resulting in considerable simulated historical runoff responses. Secondly, twentieth century land-cover and runoff coefficient changes were confronted with twentieth century changing gully morphologies. As the results show, large-scale land-cover changes and deforestation cannot explain the observed processes. The study therefore invokes interactions between authigenic factors, small-scale plot boundary changes, cropland management and sociopolitical forces to explain the gully cut processes. Finally, semi-structured interviews and sedistratigraphic analysis of three filled gullies confirm the dominant impact of (crop)land management (tillage, check dams in gullies and channel diversions) on gully cut-and-fill processes. Since agricultural land management – including land tenure and land distribution – has been commonly neglected in earlier related research, we argue therefore that it can be a very strong driver of twentieth century gully morphodynamics

An update on oxysterol biochemistry: New discoveries in lipidomics

Oxysterols are oxidised derivatives of cholesterol or its precursors post lanosterol. They are intermediates in the biosynthesis of bile acids, steroid hormones and 1,25-dihydroxyvitamin D3. Although often considered as metabolic intermediates there is a growing body of evidence that many oxysterols are bioactive and their absence or excess may be part of the cause of a disease phenotype. Using global lipidomics approaches oxysterols are underrepresented encouraging the development of targeted approaches. In this article, we discuss recent discoveries important in oxysterol biochemistry and some of the targeted lipidomic approaches used to make these discoveries