Identifiability of Control-Oriented Glucose-Insulin Linear Models: Review and Analysis

One of the main challenges of glucose control in patients with type 1 diabetes is identifying a control-oriented model that reliably predicts the behavior of glycemia. Here, a review is provided emphasizing the structural identifiability and observability properties, which surprisingly reveals that few of them are globally identifiable and observable at the same time. Thus, a general proposal was developed to encompass four linear models according to suitable assumptions and transformations. After the corresponding structural properties analysis, two minimal model structures are generated, which are globally identifiable and observable. Then, the practical identifiability is analyzed for this application showing that the standard collected data in many cases do not have the necessary quality to ensure a unique solution in the identification process even when a considerable amount of data is collected. The two minimal control-oriented models were identified using a standard identification procedure using data from 30 virtual patients of the UVA/Padova simulator and 77 diabetes care data from adult patients of a diabetes center. The identification was performed in two stages: calibration and validation. In the first stage, the average length was taken as two days (dictated by the practical identifiability). For both structures, the mean absolute error was 16.8 mg/dl and 9.9 mg/dl for virtual patients and 21.6 mg/dl and 21.5 mg/dl for real patients. For the second stage, a one-day validation window was considered long enough for future artificial pancreas applications. The mean absolute error was 23.9 mg/dl and 12.3 mg/dl for virtual patients and 39.2 mg/dl and 36.6 mg/dl for virtual and real patients. These results confirm that linear models can be used as prediction models in model-based control strategies as predictive control.Fil: Hoyos, J. D.. Universidad Nacional de Colombia. Sede Medellín; ColombiaFil: Villa Tamayo, M. F.. Universidad Nacional de Colombia. Sede Medellín; ColombiaFil: Builes Montano, C. E.. Universidad de Antioquia; ColombiaFil: Ramirez Rincon, A.. Universidad Pontificia Bolivariana; ColombiaFil: Godoy, José Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Garcia Tirado, J.. University of Virginia; Estados UnidosFil: Rivadeneira Paz, Pablo Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentin

A Comprehensive Analysis of Choroideremia: From Genetic Characterization to Clinical Practice.

Choroideremia (CHM) is a rare X-linked disease leading to progressive retinal degeneration resulting in blindness. The disorder is caused by mutations in the CHM gene encoding REP-1 protein, an essential component of the Rab geranylgeranyltransferase (GGTase) complex. In the present study, we evaluated a multi-technique analysis algorithm to describe the mutational spectrum identified in a large cohort of cases and further correlate CHM variants with phenotypic characteristics and biochemical defects of choroideremia patients. Molecular genetic testing led to the characterization of 36 out of 45 unrelated CHM families (80%), allowing the clinical reclassification of four CHM families. Haplotype reconstruction showed independent origins for the recurrent p.Arg293* and p.Lys178Argfs*5 mutations, suggesting the presence of hotspots in CHM, as well as the identification of two different unrelated events involving exon 9 deletion. No certain genotype-phenotype correlation could be established. Furthermore, all the patients´ fibroblasts analyzed presented significantly increased levels of unprenylated Rabs proteins compared to control cells; however, this was not related to the genotype. This research demonstrates the major potential of the algorithm proposed for diagnosis. Our data enhance the importance of establish a differential diagnosis with other retinal dystrophies, supporting the idea of an underestimated prevalence of choroideremia. Moreover, they suggested that the severity of the disorder cannot be exclusively explained by the genotype

The star formation history and metal content of the "Green Peas". New detailed GTC-OSIRIS spectrophotometry of three galaxies

We present deep broad-band imaging and long-slit spectroscopy of three compact, low-mass starburst galaxies at redshift z\sim0.2-0.3, also referred to as Green Peas (GP). We measure physical properties of the ionized gas and derive abundances for several species with high precision. We find that the three GPs display relatively low extinction, low oxygen abundances, and remarkably high N/O ratios We also report on the detection of clear signatures of Wolf-Rayet (WR) stars in these galaxies. We carry out a pilot spectral synthesis study using a combination of both population and evolutionary synthesis models. Their outputs are in qualitative agreement, strongly suggesting a formation history dominated by starbursts. In agreement with the presence of WR stars, these models show that these GPs currently undergo a major starburst producing between ~4% and ~20% of their stellar mass. However, as models imply, they are old galaxies having had formed most of their stellar mass several Gyr ago. The presence of old stars has been spectroscopically verified in one of the galaxies by the detection of Mg I 5167, 5173 absorption line. Additionally, we perform a surface photometry study based on HST data, that indicates that the three galaxies posses an exponential low-surface brightness envelope. If due to stellar emission, the latter is structurally compatible to the evolved hosts of luminous BCD/HII galaxies, suggesting that GPs are identifiable with major episodes in the assembly history of local BCDs. These conclusions highlight the importance of these objects as laboratories for studying galaxy evolution at late cosmic epochs.Comment: 30 pages, 9 figures and 7 tables. Accepted for publication in Ap

Anti-proliferative effect of melissa officinalis on human colon cancer cell line

Melissa officinalis L. (Lamiaceae) is consumed as a traditional herbal tea in the Mediterranean region. The cytotoxic effect of the 50% ethanolic and aqueous extract, determined by the MTT and NR assays, was evaluated in vitro on Human Colon Cancer Cell Line (HCT-116), using Triton 10% as positive control. The 50 % ethanolic extract showed significant differences after 72 hours of treatment, reducing cell proliferation to values close to 40%, even the lowest dose tested (5 μg/ml). In the MTT assay, the same extract caused the lowest cell viability with 13% at a concentration of 1000 μg/ml after 72 h of treatment, being a value lower than triton 10%. The antioxidant activity was also confirmed evaluating the capacity of the extracts to scavenge ABTS and DPPH radicals, and IC50 values were highly correlated with the total phenolic and flavonoid content. Bioassay guided fractionation led to the isolation of an anti-proliferative compound, rosmarinic acid. Its structural elucidation was performed by HPLC/DAD/ESI/MS analysis. High dose of rosmarinic acid (1000 μg/ml) was clearly cytotoxic against HCT-116 cells, with a significant decrease in cell number since the earliest time point (24 h)

Long-Term Evolution of the Aerosol Debris Cloud Produced by the 2009 Impact on Jupiter

We present a study of the long-term evolution of the cloud of aerosols produced in the atmosphere of Jupiter by the impact of an object on 19 July 2009. The work is based on images obtained during 5 months from the impact to 31 December 2009 taken in visible continuum wavelengths and from 20 July 2009 to 28 May 2010 taken in near-infrared deep hydrogen-methane absorption bands at 2.1-2.3 micron. The impact cloud expanded zonally from approximately 5000 km (July 19) to 225,000 km (29 October, about 180 deg in longitude), remaining meridionally localized within a latitude band from 53.5 deg S to 61.5 deg S planetographic latitude. During the first two months after its formation the site showed heterogeneous structure with 500-1000 km sized embedded spots. Later the reflectivity of the debris field became more homogeneous due to clump mergers. The cloud was mainly dispersed in longitude by the dominant zonal winds and their meridional shear, during the initial stages, localized motions may have been induced by thermal perturbation caused by the impact's energy deposition. The tracking of individual spots within the impact cloud shows that the westward jet at 56.5 deg S latitude increases its eastward velocity with altitude above the tropopause by 5- 10 m/s. The corresponding vertical wind shear is low, about 1 m/s per scale height in agreement with previous thermal wind estimations. We found evidence for discrete localized meridional motions with speeds of 1-2 m/s. Two numerical models are used to simulate the observed cloud dispersion. One is a pure advection of the aerosols by the winds and their shears. The other uses the EPIC code, a nonlinear calculation of the evolution of the potential vorticity field generated by a heat pulse that simulates the impact. Both models reproduce the observed global structure of the cloud and the dominant zonal dispersion of the aerosols, but not the details of the cloud morphology. The reflectivity of the impact cloud decreased exponentially with a characteristic timescale of 15 days; we can explain this behavior with a radiative transfer model of the cloud optical depth coupled to an advection model of the cloud dispersion by the wind shears. The expected sedimentation time in the stratosphere (altitude levels 5-100 mbar) for the small aerosol particles forming the cloud is 45-200 days, thus aerosols were removed vertically over the long term following their zonal dispersion. No evidence of the cloud was detected 10 months after the impact

Herramientas on-line como apoyo para el aprendizaje y autoevaluación de las asignaturas Química Farmacéutica y Farmacología en el Grado en Farmacia

Depto. de Farmacología, Farmacognosia y BotánicaFac. de FarmaciaFALSEsubmitte

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

The Southern Wide-field Gamma-ray Observatory reach for Primordial Black Hole evaporation

The Southern Wide-field Gamma-ray Observatory (SWGO) is a proposed ground-based gamma-ray detector that will be located in the Southern Hemisphere and is currently in its design phase. In this contribution, we will outline the prospects for Galactic science with this Observatory. Particular focus will be given to the detectability of extended sources, such as gamma-ray halos around pulsars; optimisation of the angular resolution to mitigate source confusion between known TeV sources; and studies of the energy resolution and sensitivity required to study the spectral features of PeVatrons at the highest energies. Such a facility will ideally complement contemporaneous observatories in studies of high energy astrophysical processes in our Galaxy