Analysis of manufacturing based on object oriented discrete event simulation

This paper describes SIMMEK, a computer-based tool for performing analysis of manufacturing systems, developed at the Production Engineering Laboratory, NTH-SINTEF. Its main use will be in analysis of job shop type of manufacturing. But certain facilities make it suitable for FMS as well as a production line manufacturing. This type of simulation is very useful in analysis of any types of changes that occur in a manufacturing system. These changes may be investments in new machines or equipment, a change in layout, a change in product mix, use of late shifts, etc. The effects these changes have on for instance the throughput, the amount of VIP, the costs or the net profit, can be analysed. And this can be done before the changes are made, and without disturbing the real system. Simulation takes into consideration, unlike other tools for analysis of manufacturing systems, uncertainty in arrival rates, process and operation times, and machine availability. It also shows the interaction effects a job which is late in one machine, has on the remaining machines in its route through the layout. It is these effects that cause every production plan not to be fulfilled completely. SIMMEK is based on discrete event simulation, and the modeling environment is object oriented. The object oriented models are transformed by an object linker into data structures executable by the simulation kernel. The processes of the entity objects, i.e. the products, are broken down to events and put into an event list. The user friendly graphical modeling environment makes it possible for end users to build models in a quick and reliable way, using terms from manufacturing. Various tests and a check of model logic are helpful functions when testing validity of the models. Integration with software packages, with business graphics and statistical functions, is convenient in the result presentation phase

Enrichment methods to detect bone marrow micrometastases in breast carcinoma patients: clinical relevance

INTRODUCTION: Improving technologies for the detection and purification of bone marrow (BM) micrometastatic cells in breast cancer patients should lead to earlier prognosis of the risk of relapse and should make it possible to design more appropriate therapies. The technique used has to overcome the challenges resulting from the small number of target cells (one per million hematopoietic cells) and the heterogeneous expression of micrometastatic cell markers. In the present study, we have assessed the clinical relevance of current methods aimed at detecting rare disseminated carcinoma cells. METHODS: BM aspirates from 32 carcinoma patients were screened for the presence of micrometastatic cells positive for epithelial cell adhesion molecule and positive for cytokeratins, using optimized immunodetection methods. A comparison with data obtained for 46 control BM aspirates and a correlation with the clinical status of patients were performed. RESULTS: We developed a sensitive and efficient immunomagnetic protocol for the enrichment of BM micrometastases. This method was used to divide 32 breast carcinoma patients into three categories according to their epithelial cell adhesion molecule status. These categories were highly correlated with the recently revised American Joint Committee on Cancer staging system for breast cancer, demonstrating the clinical relevance of this simple and reliable immunomagnetic technique. We also evaluated immunocytochemical detection of cytokeratin-positive cells and cytomorphological parameters. Immunocytochemistry-based methods for the detection of BM micrometastases did not provide any information about the clinical status of patients, but helped to refine the immunomagnetic data by confirming the presence of micrometastases in some cases. We also tested a new density gradient centrifugation system, able to enrich the tumor fraction of BM specimens by twofold to threefold as compared with standard Ficoll methods. CONCLUSION: These improved methods for the detection of micrometastatic cells in patient BM should help clinicians to predict the clinical status of breast cancer patients at the time of surgery or treatment

Usefulness of health registries when estimating vaccine effectiveness during the influenza A(H1N1)pdm09 pandemic in Norway

<p>Abstract</p> <p>Background</p> <p>During the 2009-2010 pandemic in Norway, 12 513 laboratory-confirmed cases of pandemic influenza A(H1N1)pdm09, were reported to the Norwegian Surveillance System for Communicable Diseases (MSIS). 2.2 million persons (45% of the population) were vaccinated with an AS03-adjuvanted monovalent vaccine during the pandemic. Most of them were registered in the Norwegian Immunisation Registry (SYSVAK). Based on these registries, we aimed at estimating the vaccine effectiveness (VE) and describing vaccine failures during the pandemic in Norway, in order to evaluate the role of the vaccine as a preventive measure during the pandemic.</p> <p>Methods</p> <p>We conducted a population-based retrospective cohort study, linking MSIS and SYSVAK with pandemic influenza vaccination as exposure and laboratory-confirmed pandemic influenza as outcome. We measured VE by week and defined two thresholds for immunity; eight and 15 days after vaccination.</p> <p>Results</p> <p>The weekly VE ranged from 77% to 96% when considering 15 days or more after vaccination as the threshold of immunity and from 73% to 94% when considering eight days or more. Overall, 157 individuals contracted pandemic influenza eight or more days after vaccination (8.4/100,000 vaccinated), of these 58 had onset 15 days or more after vaccination (3.0/100,000 vaccinated). Most of the vaccine failures occurred during the first weeks of the vaccination campaign. More than 30% of the vaccine failures were found in people below 10 years of age.</p> <p>Conclusions</p> <p>Having available health registries with data regarding cases of specific disease and vaccination makes it feasible to estimate VE in a simple and rapid way. VE was high regardless the immunity threshold chosen. We encourage public health authorities in other countries to set up such registries. It is also important to consider including information on underlying diseases in registries already existing, in order to make it feasible to conduct more complete VE estimations.</p

Tn1546 is part of a larger plasmid-encoded genetic unit horizontally disseminated among clonal Enterococcus faecium lineages

o determine the genetic composition of the first VanA-type plasmid (pIP816) reported, which was isolated from a clinical Enterococcus faecium (BM4147) strain in France in 1986, and to reveal the genetic units responsible for the dissemination of the vanA gene cluster by comparisons with current, published and additionally generated vanA-spanning plasmid sequences obtained from a heterogeneous E. faecium strain collection (n = 28).Plasmid sequences were produced by shotgun sequencing using ABI dye chemistry and primer walking, and were subsequently annotated. Comparative sequence analysis of the vanA region was done with published plasmids, with a partial vanA plasmid (pVEF4) reported here and to >140 kb of sequence obtained from a collection of vanA-harbouring plasmid fragments. Bioinformatic analyses revealed that pIP816 from 1986 and contemporary vanA plasmids shared a conserved genetic fragment of 25 kb, spanning the 10.85 kb vanA cluster encoded by Tn1546, and that the larger unit is present in both clinical and animal complexes of E. faecium. A new group II intron in pVEF4 was characterized. Comparative DNA analyses suggest that Tn1546 disseminates in and between clonal complexes of E. faecium as part of a larger genetic unit, possibly as a composite transposon flanked by IS1216 elements

Multivariate curve resolution of time course microarray data

BACKGROUND: Modeling of gene expression data from time course experiments often involves the use of linear models such as those obtained from principal component analysis (PCA), independent component analysis (ICA), or other methods. Such methods do not generally yield factors with a clear biological interpretation. Moreover, implicit assumptions about the measurement errors often limit the application of these methods to log-transformed data, destroying linear structure in the untransformed expression data. RESULTS: In this work, a method for the linear decomposition of gene expression data by multivariate curve resolution (MCR) is introduced. The MCR method is based on an alternating least-squares (ALS) algorithm implemented with a weighted least squares approach. The new method, MCR-WALS, extracts a small number of basis functions from untransformed microarray data using only non-negativity constraints. Measurement error information can be incorporated into the modeling process and missing data can be imputed. The utility of the method is demonstrated through its application to yeast cell cycle data. CONCLUSION: Profiles extracted by MCR-WALS exhibit a strong correlation with cell cycle-associated genes, but also suggest new insights into the regulation of those genes. The unique features of the MCR-WALS algorithm are its freedom from assumptions about the underlying linear model other than the non-negativity of gene expression, its ability to analyze non-log-transformed data, and its use of measurement error information to obtain a weighted model and accommodate missing measurements

Care transitions in the first 6 months following traumatic brain injury: Lessons from the CENTER-TBI study

Background: No large international studies have investigated care transitions during or after acute hospitalisations for traumatic brain injury (TBI).Objectives: To characterise various TBI-care pathways and the number of associated transitions during the first 6 months after TBI and to assess the impact of these on functional TBI outcome controlled for demographic and injury-related factors.Methods: This was a cohort study of patients with TBI admitted to various trauma centres enrolled in the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. Number of transitions and specific care pathways were identified. Multiple logistic regression analyses were used to assess the impact of number of transitions and care pathways on functional outcome at 6 months post-injury as assessed by the Glasgow Outcome Scale-Extended (GOSE).Results: In total, 3133 patients survived the acute TBI-care pathway and had at least one documented in-hospital transition at 6-month follow-up. The median number of transitions was 3 (interquartile range 2-3). The number of transitions did not predict functional outcome at 6 months (odds ratio 1.08, 95% confidence interval 1.09-1.18; p = 0.063). A total of 378 different care pathways were identified; 8 were identical for at least 100 patients and characterized as "common pathways". Five of these common care pathways predicted better functional outcomes at 6 months, and the remaining 3 pathways were unrelated to outcome. In both models, increased age, violence as the cause of injury, pre-injury presence of systemic disease, both intracranial and overall injury severity, and regions of Southern/Eastern Europe were associated with unfavourable functional outcomes at 6 months.Conclusions: A high number of different and complex care pathways was found for patients with TBI, particularly those with severe injuries. This high number and variety of care pathway possibilities indicates a need for standardisation and development of "common data elements for TBI care pathways" for future studies.Study registration: ClinicalTrials.gov NCT02210221.</div

First Isolation of Hepatitis E Virus Genotype 4 in Europe through Swine Surveillance in the Netherlands and Belgium

Hepatitis E virus (HEV) genotypes 3 and 4 are a cause of human hepatitis and swine are considered the main reservoir. To study the HEV prevalence and characterize circulating HEV strains, fecal samples from swine in the Netherlands and Belgium were tested by RT-PCR. HEV prevalence in swine was 7–15%. The Dutch strains were characterized as genotype 3, subgroups 3a, 3c and 3f, closely related to sequences found in humans and swine earlier. The HEV strains found in Belgium belonged to genotypes 3f and 4b. The HEV genotype 4 strain was the first ever reported in swine in Europe and an experimental infection in pigs was performed to isolate the virus. The genotype 4 strain readily infected piglets and caused fever and virus shedding. Since HEV4 infections have been reported to run a more severe clinical course in humans this observation may have public health implications