Megalencephalic leukoencephalopathy with subcortical cysts : characterization of disease variants

Objective : To provide an overview of clinical and MRI characteristics of the different variants of the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts (MLC) and identify possible differentiating features. Methods : We performed an international multi-institutional, cross-sectional observational study of the clinical and MRI characteristics in patients with genetically confirmed MLC. Clinical information was obtained by questionnaires for physicians and retrospective chart review. Results : We included 204 patients with classic MLC, 187 of whom had recessive mutations in MLC1 (MLC1 variant) and 17 in GLIALCAM (MLC2A variant) and 38 patients with remitting MLC caused by dominant GLIALCAM mutations (MLC2B variant). We observed a relatively wide variability in neurologic disability among patients with classic MLC. No clinical differences could be identified between patients with MLC1 and MLC2A. Patients with MLC2B invariably had a milder phenotype with preservation of motor function, while intellectual disability and autism were relatively frequent. Systematic MRI review revealed no MRI features that distinguish between MLC1 and MLC2A. Radiologic improvement was observed in all patients with MLC2B and also in 2 patients with MLC1. In MRIs obtained in the early disease stage, absence of signal abnormalities of the posterior limb of the internal capsule and cerebellar white matter and presence of only rarefied subcortical white matter instead of true subcortical cysts were suggestive of MLC2B. Conclusion : Clinical and MRI features did not distinguish between classic MLC with MLC1 or GLIALCAM mutations. Absence of signal abnormalities of the internal capsule and cerebellar white matter are MRI findings that point to the remitting phenotype

Megalencephalic leukoencephalopathy with subcortical cysts: Characterization of disease variants

OBJECTIVE: To provide an overview of clinical and MRI characteristics of the different variants of the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts (MLC) and identify possible differentiating features. METHODS: We performed an international multi-institutional, cross-sectional observational study of the clinical and MRI characteristics in patients with genetically confirmed MLC. Clinical information was obtained by questionnaires for physicians and retrospective chart review. RESULTS: We included 204 patients with classic MLC, 187 of whom had recessive mutations in MLC1 (MLC1 variant) and 17 in GLIALCAM (MLC2A variant) and 38 patients with remitting MLC caused by dominant GLIALCAM mutations (MLC2B variant). We observed a relatively wide variability in neurologic disability among patients with classic MLC. No clinical differences could be identified between patients with MLC1 and MLC2A. Patients with MLC2B invariably had a milder phenotype with preservation of motor function, while intellectual disability and autism were relatively frequent. Systematic MRI review revealed no MRI features that distinguish between MLC1 and MLC2A. Radiologic improvement was observed in all patients with MLC2B and also in 2 patients with MLC1. In MRIs obtained in the early disease stage, absence of signal abnormalities of the posterior limb of the internal capsule and cerebellar white matter and presence of only rarefied subcortical white matter instead of true subcortical cysts were suggestive of MLC2B. CONCLUSION: Clinical and MRI features did not distinguish between classic MLC with MLC1 or GLIALCAM mutations. Absence of signal abnormalities of the internal capsule and cerebellar white matter are MRI findings that point to the remitting phenotype

Altered Ultrasonic Vocalization and Impaired Learning and Memory in Angelman Syndrome Mouse Model with a Large Maternal Deletion from Ube3a to Gabrb3

Angelman syndrome (AS) is a neurobehavioral disorder associated with mental retardation, absence of language development, characteristic electroencephalography (EEG) abnormalities and epilepsy, happy disposition, movement or balance disorders, and autistic behaviors. The molecular defects underlying AS are heterogeneous, including large maternal deletions of chromosome 15q11–q13 (70%), paternal uniparental disomy (UPD) of chromosome 15 (5%), imprinting mutations (rare), and mutations in the E6-AP ubiquitin ligase gene UBE3A (15%). Although patients with UBE3A mutations have a wide spectrum of neurological phenotypes, their features are usually milder than AS patients with deletions of 15q11–q13. Using a chromosomal engineering strategy, we generated mutant mice with a 1.6-Mb chromosomal deletion from Ube3a to Gabrb3, which inactivated the Ube3a and Gabrb3 genes and deleted the Atp10a gene. Homozygous deletion mutant mice died in the perinatal period due to a cleft palate resulting from the null mutation in Gabrb3 gene. Mice with a maternal deletion (m−/p+) were viable and did not have any obvious developmental defects. Expression analysis of the maternal and paternal deletion mice confirmed that the Ube3a gene is maternally expressed in brain, and showed that the Atp10a and Gabrb3 genes are biallelically expressed in all brain sub-regions studied. Maternal (m−/p+), but not paternal (m+/p−), deletion mice had increased spontaneous seizure activity and abnormal EEG. Extensive behavioral analyses revealed significant impairment in motor function, learning and memory tasks, and anxiety-related measures assayed in the light-dark box in maternal deletion but not paternal deletion mice. Ultrasonic vocalization (USV) recording in newborns revealed that maternal deletion pups emitted significantly more USVs than wild-type littermates. The increased USV in maternal deletion mice suggests abnormal signaling behavior between mothers and pups that may reflect abnormal communication behaviors in human AS patients. Thus, mutant mice with a maternal deletion from Ube3a to Gabrb3 provide an AS mouse model that is molecularly more similar to the contiguous gene deletion form of AS in humans than mice with Ube3a mutation alone. These mice will be valuable for future comparative studies to mice with maternal deficiency of Ube3a alone

Total production maintenance and robust scheduling for a production system efficiency increasing

In the paper, the proposition of application of two methodologies: the predictive scheduling and Total Productive Maintenance – TPM to increase efficiency of a production system is presented. To assess wastes due to unplanned events in the machine’s work the Overall Equipment Effectiveness (OEE) indicator is applied. Any failure of a bottle neck decreases value of the OEE. In this paper, the problem of predicting a time of the bottle neck failure is considered. In the paper, models of a production system and failures are presented. For the bottle neck various reliability characteristics are computed: the probability that, beginning with moment t0 , the first failure occurs after given time t, probability that in the interval [f ,g], there occurs at least one failure, failure intensity function, Mean Time To Failure (MTTF) and Mean Time of Repair (MTTR). Having the MTTF and MTTR of the bottle neck, a robust schedule is generated. At the time of predicted failure, preventive actions and technical survey of the machine are scheduled. In the second paper a numerical example is given

A numerical example of total production maintenance and robust scheduling application for a production system efficiency increasing

In the paper, the proposition of application of two methodologies: the predictive scheduling and Total Productive Maintenance - TPM to increase efficiency of a production system is presented. In this paper, an example of problem of predicting a time of a bottle neck failure is presented. Using the Statistica program, histograms that show the graphical relationship of a number of observations and failure-free times of the bottle neck for historical periods are created. The fitting of the histograms to the theoretical distributions: normal, exponential, gamma and Weibull using appropriate tests (for example the Kolmogorov-Smirnov test for normal distribution) is researched. After finding distribution and setting parameters for historical periods, for the next scheduling horizon values of parameters are extrapolated using the regression method in the Statistica program. For the bottle neck various reliability characteristics are computed. Having the Mean Time To Failure (MTTF) and Mean Time of Repair (MTTR) of the bottle neck, robust schedule is generated. At the time of the predicted failure, preventive actions and technical survey of the machine are scheduled. The production system is modeled in the simulation program - Enterprise Dynamics 8.1

Analysis of human operators and industrial robots performance and reliability

In the article problems related to human labor and factors affecting the increasing use of industrial robots are discussed. Since human factors affect the production processes stability, robots are preferred to apply. The application of robots is characterized by higher performance and reliability comparing to human labor. The problem is how to determine the real difference in work efficiency between human operator and robot. The aim of the study is to develop a method that allows clearly definition of productivity growth associated with the replacement of human labor by industrial robots. Another aim of the paper is how to model robotized and manual operated workstation in a computer simulation software. Analysis of the productivity and reliability of the hydraulic press workstation operated by the human operator or an industrial robot, are presented. Simulation models have been developed taking into account the availability and reliability of the machine, operator and robot. We apply OEE (Overall Equipment Effectiveness) indicator to present how availability and reliability parameters influence over performance of the workstation, in the longer time. Simplified financial analysis is presented considering different labor costs in EU countries

The analysis of surface skin temperature in patients with chronic ischemia of lower limbs

Niedokrwienie kończyn dolnych jest chorobą spowodowaną zmianami w tętnicach. Postęp w motoryzacji, nieprawidłowe odżywianie, stres, palenie papierosów i inne nałogi sprzyjają rozwojowi miażdżycy kończyn dolnych. Celem pracy było przedstawienie wstępnych wyników badań wpływu przewlekłego niedokrwienia kończyn dolnych na dynamikę zmian temperatury w obrębie wybranych obszarów ciała. Dynamika i progresja zmian miażdżycowych oraz spadek temperatury w obrębie kończyn dolnych, są różne w zależności od stopnia niedokrwienia. W pracy przedstawiono porównanie badań termowizyjnych przeprowadzonych wśród osób chorych i zdrowych.The ischaemia of lower limbs is a disease caused by arteries lesions. The motorization, incorrect nutrition, stress, smoking and other addictions are factors that thay may lead to the progress of the arteriosclerosis of lower limbs. The aim of the paper was to present preliminary results of the studies on the influence of chronic ischaemia of lower limbs on the temperature distribution within the selected body areas. The dynamics and the progression of atherosclerotic changes, as well as the decrease of temperature of the lower limbs skin, depend upon the progress of ischaemia. The comparison of thermovision examinations performed on ill and healthy people, is presented