Simulation and optimization of dynamic flux balance analysis models using an interior point method reformulation

This work presents a novel, differentiable, way of solving dynamic Flux Balance Analysis (dFBA) problems by embedding flux balance analysis of metabolic network models within lumped bulk kinetics for biochemical processes. The proposed methodology utilizes transformation of the bounds of the embedded linear programming problem of flux balance analysis via a logarithmic barrier (interior point) approach. By exploiting the first-order optimality conditions of the interior-point problem, and with further transformations, the approach results in a system of implicit ordinary differential equations. Results from four case studies, show that the CPU and wall-times obtained using the proposed method are competitive with existing state-of-the-art approaches for solving dFBA simulations, for problem sizes up to genome-scale. The differentiability of the proposed approach allows, using existing commercial packages, its application to the optimal control of dFBA problems at a genome-scale size, thus outperforming existing formulations as shown by two dynamic optimization case studies.• R. Conejeros would like to thank CONICYT’s research grant FONDECYT 1151295 for funding this research. • F. Scott gratefully acknowledges financial support from CONICYT (Proyectos REDES ETAPA INICIAL, Convocatoria 2017, REDI170254)

Constrained NLP via gradient flow penalty continuation: Towards self-tuning robust penalty schemes

This work presents a new numerical solution approach to nonlinear constrained optimization problems based on a gradient flow reformulation. The proposed solution schemes use self-tuning penalty parameters where the updating of the penalty parameter is directly embedded in the system of ODEs used in the reformulation, and its growth rate is linked to the violation of the constraints and variable bounds. The convergence properties of these schemes are analyzed, and it is shown that they converge to a local minimum asymptotically. Numerical experiments using a set of test problems, ranging from a few to several hundred variables, show that the proposed schemes are robust and converge to feasible points and local minima. Moreover, results suggest that the GF formulations were able to find the optimal solution to problems where conventional NLP solvers fail, and in less integration steps and time compared to a previously reported GF formulation

Fricke and polymer gel 2D dosimetry validation using Monte Carlo simulation

Complexity in modern radiotherapy treatments demands advanced dosimetry systems for quality control. These systems must have several characteristics, such as high spatial resolution, tissue equivalence, three-dimensional resolution, and dose-integrating capabilities. In this scenario, gel dosimetry has proved to be a very promising option for quality assurance. In this study, the feasibility of Fricke and polymer gel dosimeters suitably shaped in form of thin layers and optically analyzed by visible light transmission imaging has been investigated for quality assurance in external radiotherapy. Dosimeter irradiation was carried out with a 6-MV photon beam (CLINAC 600C). The analysis of the irradiated dosimeters was done using two-dimensional optical transmission images. These dosimeters were compared with a treatment plan system using Monte Carlo simulations as a reference by means of a gamma test with parameters of 1 mm and 2%. Results show very good agreement between the different dosimetric systems: in the worst-case scenario, 98% of the analyzed points meet the test quality requirements. Therefore, gel dosimetry may be considered as a potential tool for the validation of other dosimetric systems.Fil: Vedelago, José Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Chacón Obando, D.. Universidad Nacional. Physics Department; Costa Rica. Universidad Nacional de Córdoba; ArgentinaFil: Malano, Francisco Mauricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Conejeros, R.. Servicio de Radioterapia, Icos. Temuco, Chile;Fil: Figueroa, R.. Universidad de la Frontera; ChileFil: Garcia, D.. Servicio de Imagenes por Resonancia Magnética; ChileFil: González, G.. Servicio de Imagenes por Resonancia Magnética; ChileFil: Romero, Marcelo Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Santibañez, M.. Servicio de Imagenes por Resonancia Magnética; ChileFil: Strumia, Miriam Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Velásquez, J.. Servicio de Radioterapia; ChileFil: Mattea, Facundo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Valente, M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Universidad de La Frontera. Departamento de Ciencias Físicas; Chil

Epidemiological profile of deaths after the 2010 earthquake in Chile

Indexación: Web of Science; ScieloBackground: On February 27, 2010 a powerful earthquake followed by a tsunami stroke Chile. The study of mortality during this emergency can provide important public health information. Aim: To describe the main characteristics of people who died during the earthquake and the following three months. Material and Methods: Cross sectional analysis of death records databases obtained from Department of Health Statistics and Information of the Ministry of Health and the Coroner office. Results: Until May 25,2010, 505 corpses were completely identified. Seventy two of these corresponded to people aged 80 years or more. The higher age adjusted death rates per 100,000 inhabitants were observed among subjects aged more than 80 years and those aged 70 to 79 years (22.6 and 7.7 respectively). The higher rates of deaths were observed in regions where the earthquake had a higher intensity and coastal regions affected by the tsunami. The causes of death were trauma in 75% of cases and drowning in 25%. There was no association between the Mercalli scale of earthquake intensity and rates of death. Among deceased subjects, there was a concentration of unemployed, under educated and low socioeconomic status subjects. Conclusions: After the earthquake, the higher rates of deaths occurred among older people and in the region of the epicenter of the earthquake. Most deaths were due to trauma.http://ref.scielo.org/gmq43

Energy transfer, structural and luminescent properties of the color tunable Phosphor Y2WO6:Sm3+

Inorganic phosphors based on monoclinic Y2WO6 doped with Sm3þ ions were prepared via conventional solid-state reactions at high temperature. A total of six samples were obtained with different Sm3þ concentrations (0e9%). The purity of the as-prepared phases was checked by powder X-ray diffraction (PXRD). The excitation, emission, and time-resolved emission spectra were examined in detail. The experimental decay curves were fitted to the InokutieHirayama model, showing that the Sm3þ ions form clusters at all compositions. Periodic hybrid density functional theory calculations were also carried out on the undoped material and on 144-atom supercells of stoichiometry Y1.9375Sm0.0625WO6 and Y1.875Sm0.125WO6. The different coordination environments at the Y1, Y2 and Y3 sites are analysed in detail. The calculated structure and band gap of Y2WO6 are in good agreement with experiment with one potentially important discrepancy in a Y3eO bond length. The thermodynamically favoured substitution sites for Sm, Y2 and Y3, in the supercell are not those observed under the preparation conditions used here, since the experimental Rietveld analysis suggests occupation of Y1 at all concentrations. Analogous calculations for the Eu- doped system highlight marked differences between Eu and Sm despite their similar ionic sizes. The calculated densities of states show the position of the 4f levels in the band gap depend on the sites occupied by the dopants and thus expect marked differences in the luminescence spectra, opening up possibilities for tuning device performance

Rapid niche expansion by selection on functional genomic variation after ecosystem recovery

It is well recognized that environmental degradation caused by human activities can result in dramatic losses of species and diversity. However, comparatively little is known about the ability of biodiversity to re-emerge following ecosystem recovery. Here, we show that a European whitefish subspecies, the gangfisch Coregonus lavaretus macrophthalmus, rapidly increased its ecologically functional diversity following the restoration of Lake Constance after anthropogenic eutrophication. In fewer than ten generations, gangfisch evolved a greater range of gill raker numbers (GRNs) to utilize a broader ecological niche. A sparse genetic architecture underlies this variation in GRN. Several co-expressed gene modules and genes showing signals of positive selection were associated with GRN and body shape. These were enriched for biological pathways related to trophic niche expansion in fishes. Our findings demonstrate the potential of functional diversity to expand following habitat restoration, given a fortuitous combination of genetic architecture, genetic diversity and selection

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)