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La creciente demanda de los consumidores de alimentos más nutritivos, ingredientes de origen natural y etiquetas más limpias está empujando a las industrias de alimentos y cosméticos a pasar del uso de colorantes artificiales a alternativas de origen natural. En este contexto, la industria busca continuamente fuentes de colorantes más estables, con especial interés en las fuentes vegetales. La vibrante biodiversidad que se encuentra en el Perú representa una emocionante oportunidad económica. En esta revisión, destacamos cultivos peruanos seleccionados con excelente potencial para su uso como fuentes de colorantes para aplicaciones industriales, con algunas fuentes que se estudian ampliamente y otras que reciben atención en años más recientes. El maíz morado, un cultivo nativo de la región de los Andes, es una rica fuente de pigmentos con gran estabilidad y una larga historia de uso en diferentes aplicaciones alrededor del mundo. Las papas de pulpa coloreada, cultivos andinos subutilizados, pueden expresar diferentes colores debido a sus perfiles de pigmentos variados. Sauco, la baya del saúco peruana, tiene una fuerte actividad antioxidante y un perfil de pigmento único que le da su característico color negro-púrpura. Las especies de Berberis, una clase diversa de arbustos con bayas altamente pigmentadas, se pueden usar directamente como aditivos de color sin necesidad de procedimientos de extracción. Huito, una fruta poco estudiada originaria del Amazonas es naturalmente incolora, pero puede volverse azul cuando se expone al oxígeno o a los aminoácidos y puede expresar diferentes tonalidades según la fuente del grupo de aminas primarias. En general, el maíz morado, las papas de pulpa coloreada, el sauco, las especies de Berberis y el huito son fuentes peruanas prometedoras de colorantes naturales para aplicaciones alimentarias y cosméticas debido a su versatilidad, estabilidad y atractivas características de color.

Globally, the reforms of healthcare systems aim to bring back the patient at the centre of these organisations after the issues related to the COVID-19 outbreak. The patient returns to be fully considered, as an individual whose must be protected physical and psychological health as well as social well-being. Humanization of care is returning to the foreground. For centuries, art has been used throughout Europe in the health context for its power to support patients in their disease. Today, this approach can be rediscovered in historical hospitals, where tradition, art and assistance coexist. This study aims to investigate the interest for the development of projects for the humanization of care exploiting the artistic heritage of the historical hospitals owned by Health Authorities. The cross-case analysis was chosen as study design. The case studies are the historical hospitals in the city centre of Venice, Florence, and Rome. The evaluation of the proposal was carried out through semi-structured interviews with the general managers of the Health Authorities, the medical directors of the selected hospitals and the delegates for the protection and promotion of cultural heritage. The results were analysed using a qualitative model (coding). All respondents welcomed the proposal to launch projects for the humanization of care that foresee the use of the artistic heritage of the historical hospitals to involve patients in the field of health care. Interviewees expressed the desire to invest human and structural resources in the development of these projects. Moreover, directors suggest choosing a specific target with which to start the experimentation and to dispense a specific training to future engaged social and health personnel. The implementation of projects for the humanization of care using the artistic heritage of historical hospitals can be replicated worldwide where healthcare institutions have a cultural wealth to be handed down, shared and valued. Key messages • In the post COVID-19 era, it is strategic to exploit artistic heritage owned by the Health Authority for the positive impact in the patient’s experience. • Artistic heritage claims its role as a health service for supporting patients, caregivers and also health workforce.

During COVID-19 pandemic, health and social condition of frail elderly got worse at worldwide level. This aggravation was due both to isolation and higher mortality rate for COVID-19, influenced by the widespread condition of comorbidity in this segment of population. The progressive change of needs in this target weren't matched with a prompt and adequate response, which could guarantee the taking charge of frail elderly. Personal budget is a tool for integrating public health, social assistance and family efforts on the international scene. In the Italian context, it is emerging as means to program and coordinate economic and professional, institutional, and personal resources, finalising them to provide a personalised pathway. Research aims to value the contribution of personal budget association to effectiveness and efficacy of personalised pathway for frail elderlies in early supported discharges. A research-intervention approach was done. Personal budget was applied to a significant sample of cases of personalised pathways for frail elderly in supported discharge in the Local Health District of Teramo. The study compared used resources and obtained health outcomes between the sample and a control group. The application of the personal budget permits the immediate maximisation of resources use and the quantification of the deviation between the available and the needed resources for provision of personalised pathway. Moreover, this tool supported the planning of services, the integration of health and social actions, the monitoring of adherence to planned programmes and the application of corrective mechanisms, if these are necessary, improving the health outcomes. Personal budget contributes to increase the integrated and continued taking charge of frail elderly in supported discharges in the short-medium term. Globally, this tool could be an organisational and economic answer for responding in a sustainable way to international increasing of life expectancy. Key messages • Personal budget manages and controls both health and social activities and resources. • Personal budget supports the establishment of an integrated and continuous taking charge system of the frail elderly.

Introduction Colorectal cancer (CRC) is one of the major causes of death worldwide. Previous research reported differences in screening adherence both by gender and socioeconomic determinants. However, little is known about the extent to which Health Literacy (HL) may affect gender differences in CRC screening rates. Here, we aimed to assess HL levels in both genders and their relations with CRC screening adherence. Methods The study was performed within the Tuscan population sample selected in the Italian Behavioral Risk Factor Surveillance System (PASSI - Progress by local health units toward a healthier Italy) in 2017-2019. Socioeconomic status was measured by education level, occupation, financial status, and nationality, while HL by the Italian version of the 6-items European Health Literacy Survey Questionnaire (HLS-EU-Q6). Multivariate analysis was performed to investigate associations between CRC screening rates, social determinants, and HL. Results Among 4,268 people aged 50-69 years included in PASSI, 64% undergo to CRC screening in the 2 years preceding the interview. No statistically significant differences in screening adherence were found by gender. In the multivariate analysis, the odds of adherence to CRC screening increased in both genders for being aged 60-69 years (Males: OR 1.43, 95% CI 1.12-1.82; Females: OR 1.72, 95% CI 1.37-2.14) and high education level (Males: OR 1.34, 95% CI 1.08-1.66; Females: OR 1.30, 95% CI 1.05-1.60). Males with a poor financial status and females with a low HL level were less likely to undergo CRC screening (OR 0.71, 95% CI 0.57-0.88 and OR 0.68 95% CI 0.49-0.95 respectively). Conclusions Our findings suggest that adherence to CRC screening is associated with HL in females only, while it depends on financial status in males. Therefore, gender specific interventions, tailored on different factors, are needed to increase the CRC screening rates. Key messages

Introduction Patients treated with Immunocheckpoint Inhibitors (ICI) can develop adverse cardiovascular events, most frequently myocarditis, but also arrhythmias, conduction abnormalities, pericarditis, Takotsubo syndrome, ACS, heart failure, cardiac arrest. Myocarditis occurs early, within the first 3–4 administrations of therapy, and is fraught with a high mortality rate. Case Presentation 80–year–old patient with renal pelvic carcinoma who underwent nephroureterectomy and subsequent adrenalectomy. Twenty days after the first cycle of Pembrolizumab, the patient is admitted to cardiology for syncope and ECG finding of Left Posterior Fascicular Block (LPFB) and right bundle branch block (RBBB) with significant increase in troponin without any alterations in regional kinetics and normal ventricular function (EF). The patient also complains of widespread muscle pain and severe hyponatremia on blood tests. On ECG monitoring, alternation of RBBB with associated LPFB and Left Posterior Fascicular Block, left bundle branch block, first and second degree atrio–ventricular block (AV block) and on day II appearance of complete paroxysmal AV block controlled with temporary pacemaker implantation. On the 4th day, we documented changes in the segmental motion of the left ventricle (LV) and progressive gradual worsening of the EF. During the hospitalization the patient manifested episodes of general malaise with profuse sweating and marked hypotension with possible SIADH picture. In suspicion of acute myocarditis, peripheral myositis and possible Pembrolizumab SIADH, the patient was treated with high dose methylprednisolone (1000 mg / day) with little benefit. On the 6th day the patient was found in critical condition, severely suffering, hypotensive and oliguric, resigned herself. Conclusions Our case highlights how even a single dose of Pembrolizumab can trigger an acute inflammatory pattern affecting the myocardium with prevalent involvement of the conduction tissue even before the appearance of alterations in the kinetics and ventricular dysfunction. During ICI therapy cycles it is therefore important to monitor the ECG and troponin levels in order to be able to diagnose myocardial involvement early. In fact, although this complication is rare, it is burdened by a high mortality rate. The only treatment currently available involves the suspension of immunotherapy and the administration of high–dose methylprednisolone.

This systematic review and meta-analysis aimed at evaluating the role of sleep disturbances and sleep disorders in influencing presence and intensity of chronic postsurgical pain (CPSP). We included cohort studies which enrolled adults, assessed sleep disturbances or disorders before surgery, measured pain intensity, presence of pain, or opioid use at least three months after surgery. Eighteen studies were included in a narrative synthesis and 12 in a meta-analysis. Sleep disturbances and disorders were significantly related to CPSP, with a small effect size, r = 0.13 (95% CI 0.06-0.20). The certainty of evidence was rated low due to risk of bias and heterogeneity. In subgroup analyses the above association was significant in studies that used pain intensity as the outcome, but not in those that used presence of pain; in studies on patients who underwent total knee arthroplasty or other surgeries, but not in those on patients who had breast cancer surgery or total hip arthroplasty; in the single study that assessed insomnia and in studies that assessed sleep disturbances as predictors. A meta-regression showed that the follow-up length was positively associated with the overall estimate. Our findings suggest that presurgical sleep disturbances and disorders should be evaluated to detect patients at risk for CPSP. Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=272654.

The installation of new renewable power plants in Italy is currently hindered by various concurrent factors, the length of the authorization process above all. The average time to authorize a wind farm is about five and a half years, mainly due to the binding judgment of the EIA (Environmental Impact Assessment). Italy however is now in a phase where many of the first-installed wind farms are close to their end of life. In this perspective, a promising solution is given by the re-powering of existing wind farms, since they can access a simplified authorization procedure under the Legislative Decree 08/11/2021, n. 199 et seq., which reduces by one third the bureaucratic burden and it lets non-binding the evaluation of the landscape authorities. Moving from this background, the study provides a feasibility study on the re-powering of Italian wind farms. Starting from the database available at GSE (Gestore dei Servizi Energetici), a new re-powering scenario has been defined, accounting for the constraints on the site area, number and dimension of the turbines imposed by the art. 32 of Law 29/07/2021, n. 108. The effectiveness of the re-powering intervention has been evaluated in terms of energetic yield, considering the increased capacity factor of the new turbines, economic revenue and environmental footprint. To verify its feasibility on a real application, a wind farm owned by AGSM-AIM S.p.A., for which wind, terrain, and production data were available, has been selected. Different plant layouts have been analyzed in the WindPro software, and compared in terms of power, producibility and capacity factor. The feasibility of the different layouts has also been verified by on-field inspections.

In this work, the topological derivatives of L2 and energy norms associated with the solution to Kirchhoff and Reissner-Mindlin plate bending models are introduced. Based on existing theoretical results, closed forms of the sensitivities are presented. A zero-order term is introduced in the equilibrium equations, which allows for adapting the obtained sensitivities to the context of topology optimization of plates under elastic support and free vibration condition as well. The resulting analytical formulae are used together with a level-set domain representation method to devise a simple topology design algorithm. Several finite element-based representative numerical experiments are presented showing its applications to the compliance minimization and eigenvalue maximization of Kirchhoff as well as Reissner-Mindlin plate structures under bending effects. Fil: Carvalho, F. S.. Universidade do Brasília; Brasil Fil: Ruscheinsky, D.. Universidade do Brasília; Brasil Fil: Giusti, Sebastian Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigación y Tecnología Química. Universidad Tecnológica Nacional. Facultad Regional Córdoba. Centro de Investigación y Tecnología Química; Argentina Fil: Anflor, Carla. Universidade do Brasília; Brasil Fil: Novotny, A. A.. Ministério da Ciência, Tecnologia e Inovações. Laboratório Nacional de Computação Científica; Brasil

PurposeThe purpose of this study is to solve the inverse homogenization problem, or so-called material design problem, using the topological derivative concept.Design/methodology/approachThe optimal topology is obtained through a relaxed formulation of the problem by replacing the characteristic function with a continuous design variable, so-called density variable. The constitutive tensor is then parametrized with the density variable through an analytical interpolation scheme that is based on the topological derivative concept. The intermediate values that may appear in the optimal topologies are removed by penalizing the perimeter functional.FindingsThe optimization process benefits from the intermediate values that provide the proposed method reaching to solutions that the topological derivative had not been able to find before. In addition, the presented theory opens the path to propose a new framework of research where the topological derivative uses classical optimization algorithms.Originality/valueThe proposed methodology allows us to use the topological derivative concept for solving the inverse homogenization problem and to fulfil the optimality conditions of the problem with the use of classical optimization algorithms. The authors solved several material design examples through a projected gradient algorithm to show the advantages of the proposed method.

A path-following strategy based on an energy release criterion is proposed and implemented in an augmented Lagrangian formulation to model localized cohesive cracks. The model is formulated in a rigourous variational framework of continuous spaces. A procedure for the solution of the proposed formulation in a continuous spaces context is also presented. The discrete form of the problem for the implementation within the finite element method is also exposed. The ability and robustness of the proposed method to track equilibrium paths including snap-back phenomenon are analyzed and discussed by means of several numerical tests. The restriction based on an energy release criterion is introduced in the formulation by using a augmented Lagrangian method. The effect of the interpolation order for the Lagrange multiplier (so-called Lagrange field), its influence on the proposed constraint equation and the mesh density dependency are studied and illustrated in the numerical simulations. Different crack patterns are analyzed and some recommendations concerning the interpolation degree that should be used for the Lagrangian field to avoid spurious energy release are also included. Fil: Labanda, Nicolás Agustín. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Instituto de Estructuras "Ing. Arturo M. Guzmán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina Fil: Giusti, Sebastian Miguel. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina Fil: Luccioni, Bibiana Maria. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Instituto de Estructuras "Ing. Arturo M. Guzmán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina

Topology optimization is a technique in the engineering area that allows obtaining optimal designs of devices, mechanisms, complex structures and even design the microstructure of an auxetic material. Classically, the focus was made on considering the problem of obtaining such designs comprised of only one material. More recently, some efforts have been made to incorporate more than one material to the optimization problem. The present work addresses the topology optimization problem considering multiple materials on a fixed project domain. For the geometric description of the material domains, the concept of multiple level-sets has been used, meanwhile, its nucleation and evolution are governed by functions constructed from the topological derivative of a functional to be minimized. The topological optimization algorithm developed to solve the multi-material topological optimization problem is described and its optimality condition is well established. Numerical examples applied to planar elasticity, bending plate, bi-dimensional steady-state heat transfer and optimal design of piezoelectric actuator problems are presented.

Background Lenvatinib is a multi-kinase inhibitor approved for patients with radioactive iodine (RAI)–resistant differentiated thyroid cancer (DTC). Before the drug approval from the Italian National Regulatory Agency, a compassionate use programme has been run in Italy. This retrospective study aimed to analyse data from the first series of patients treated with lenvatinib in Italy. Methods The primary aim was to assess the response rate (RR) and progression-free survival (PFS). Secondary end-points include overall survival (OS) and toxicity data. Results From November 2014 to September 2016, 94 patients were treated in 16 Italian sites. Seventeen percent of patients had one or more comorbidities, hypertension being the most common (60%). Ninety-eight percent of patients were treated by surgery, followed by RAI in 98% of cases. Sixty-four percent of patients received a previous systemic treatment. Lenvatinib was started at 24 mg in 64 subjects. Partial response and stable disease were observed in 36% and in 41% of subjects, respectively; progression was recorded in 14% of patients. Drug-related side-effects were common; the most common were fatigue (13.6%) and hypertension (11.6%). Overall, median PFS and OS were 10.8 months (95% confidence interval [CI], 7.7–12.6) and 23.8 months (95% CI, 19.7–25.0) respectively. Conclusion Lenvatinib is active and safe in unselected, RAI-refractory, progressive DTC patients in real-life setting. RR and PFS seem to be less favourable than those observed in the SELECT trial, likely due to a negative selection that included heavily pretreated patients or with poor performance status.

Aims: We present the second AGILE-GRID catalogue (2AGL) of γ-ray sources in the energy range 100 MeV-10 GeV. Methods: With respect to previous AGILE-GRID catalogues, the current 2AGL catalogue is based on the first 2.3 years of science data from the AGILE mission (the so-called pointing mode) and incorporates more data and several analysis improvements, including better calibrations at the event reconstruction level, an updated model for the Galactic diffuse γ-ray emission, a refined procedure for point-like source detection, and the inclusion of a search for extended γ-ray sources. Results: The 2AGL catalogue includes 175 high-confidence sources (above 4σ significance) with their location regions and spectral properties and a variability analysis with four-day light curves for the most significant. Relying on the error region of each source position, including systematic uncertainties, 122 sources are considered as positionally associated with known counterparts at different wavelengths or detected by other γ-ray instruments. Among the identified or associated sources, 62 are active galactic nuclei (AGNs) of the blazar class. Pulsars represent the largest Galactic source class, with 41 associated pulsars, 7 of which have detected pulsation; 8 supernova remnants and 4 high-mass X-ray binaries have also been identified. A substantial number of 2AGL sources are unidentified: for 53 sources no known counterpart is found at different wavelengths. Among these sources, we discuss a subclass of 29 AGILE-GRID-only γ-ray sources that are not present in 1FGL, 2FGL, or 3FGL catalogues; the remaining sources are unidentified in both 2AGL and 3FGL catalogues. We also present an extension of the analysis of 2AGL sources detected in the energy range 50-100 MeV. Full Tables 10 and 11 (the catalog) are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/627/A13

This work is focused on the study of the thermal-structural behavior of a thermal isolator device employed in a monopropellant thruster for space applications. Engines of this kind are widely used to perform attitude corrections in artificial satellites. Their operating principle is based on the catalytic decomposition of the fuel (hydrazine), producing gasification with a consequent heat generation. These gases are properly conducted to a nozzle to produce thrust. A couple of redundant solenoid on-off electro-valves, in a serial configuration, are used to control the fuel supply system. To avoid leak risk in this system, soft seals are also used. Duration and performance of this kind of engine rely on two main aspects. The first one is the number of cold ignitions. When the engine starts at low temperature conditions, the catalytic bed is subjected to a thermal transient (high gradient—hundreds of∘C/s) which generates a breakage of grains, causing low size particles to fill the inter-granular spaces, clogging the downstream gas flow. The second aspect to consider in the reduction of the life span is the loss of reliability in the soft seals used in the fuel supply system due to high temperature degradation. Such degradation can drive the module out of service, generate a catastrophic failure in the reactor, or lead to mission stoppage. A thermal isolator is used to protect the seals from a premature degradation due to thermal effects. Its structural design is optimized by using a novelty structural optimization methodology based on topological sensitivity analysis in this work. This analysis allows achieving the best structural configuration that minimizes the temperature field around the seals and also the isolator weight. Finally, a thermal and structural evaluation of the monopropellant thruster is presented in order to validate the structural strength and integrity. Inertial forces due to high G’s are considered in this analysis.

This paper presents a new semi-concurrent multi-scale model to study the behaviour of composite materials in softening regime. A mixed formulation is used to simulate discontinuities in both scales. The traction over the crack is included as a unknown field in the equations system of the problem, and the jump displacement across the discontinuity is obtained with a cohesive constitutive relation (traction-separation law).Axiomatic variational principles and the injection concept are used and formulated to get an objective model with respect to the representative volume element size (RVE). The projected stress over the normal vector of the macro discontinuity is injected in the localized domain in the RVE, obtaining as a dual variable the jump of the displacement field in the macro structure. In this way, during the stable phase of the behaviour, the scale transition is performed in the classical way injecting the strain tensor and obtaining the stress tensor as a dual variable. At the beginning of the unstable regime, the transition between the scales is defined by injecting the traction (stress projection on the normal vector to the crack) in the localization domain in the micro scale and the displacement jump at the macro scale is obtained as a dual variable. This new concept leads to a new multi-scale approach with an hybrid injection.The basic equations of the model are derived, and finally some numerical examples are developed, showing the objectivity of the homogenized response of composite material problems that involve strain localization at the macro-scale. Fil: Labanda, Nicolás Agustín. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Instituto de Estructuras "Ing. Arturo M. Guzmán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina Fil: Giusti, Sebastian Miguel. Universidad Tecnológica Nacional. Facultad Regional Córdoba. Departamento de Ingeniería Civil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina Fil: Luccioni, Bibiana Maria. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Instituto de Estructuras "Ing. Arturo M. Guzmán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina

Objective Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and non-reproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation. Design Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals. Methods We performed a detailed phenotyping of 503 IHH patients with: (1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; (2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects. Cohort was divided on IHH onset (PPO, pre-pubertal onset or AO, adult onset) and olfactory function: PPO-nIHH (n = 275), KS (n = 184), AO-nIHH (n = 36) and AO-doIHH (AO-IHH with defective olfaction, n = 8). Results 90% of patients were classified as PPO and 10% as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were also found among the AO-IHH. Mean age at diagnosis was significantly earlier and more frequently associated with congenital hypogonadism stigmata in patients with Kallmann’s syndrome (KS). Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are significantly associated with AO-IHH rather than PPO-IHH. Conclusions Patients with KS are more prone to develop a severe and complex phenotype than nIHH. The presence of typical extra-gonadal defects and familiarity for PPO-IHH among the AO-IHH patients indicates a common predisposition with variable clinical expression. Overall, these findings improve the understanding of IHH and may have a positive impact on the management of patients and their families.

Aim The aim of this study was investigate the effect of photodynamic therapy (PDT) using curcumin (C) as a photosensitizing agent irradiated with an LED (L) in the blue wavelength as a light source on a standard and clinical isolate of Streptococcus mutans (S. mutans) in a planktonic suspension model. Materials and methods Suspensions of both strains were divided into 4 groups as follows: absence of C and L (control group: C–L–), with C and without L (C group: C+L–), absence of C with L (L group: C–L+) and presence of C and L (PDT group: C+L+). Three different concentrations of curcumin (0.75 mg/ml, 1.5 mg/ml and 3 mg/ml) and three light fluences of studied light source (24, 48 and 72 J cm–2) were tested. Aliquots of each studied group was plated in BHI agar and submitted to colony forming units counting (CFU/ml) and the data transformed into logarithmical scale. Results A high photoinactivation rate of more than 70% was verified to standard S. mutans strain submitted to PDT whereas the clinical isolate showed a lower sensitivity to all the associations of curcumin and LED. A slight bacterial reduction was verified to C+L– and C–L+, demonstrating no toxic effects to the isolated application of light and photosensitizer to both S. mutans strains tested. Conclusion Photodynamic therapy using a combination of curcumin and blue LED presented a substantial antimicrobial effect on S. mutans standard strain in a planktonic suspension model with a less pronounced effect on its clinical isolate counterparts due to resistance to this alternative approach. Clinical significance Alternative antimicrobial approaches, as photodynamic therapy, should be encouraged due to optimal results against cariogenic bacteria aiming to prevent or treat dental caries. How to cite this article Tonon CC, Paschoal MA, Correia M, Spolidório DMP, Bagnato VS, Giusti JSM, Santos-Pinto L. Comparative Effects of Photodynamic Therapy mediated by Curcumin on Standard and Clinical Isolate of Streptococcus mutans. J Contemp Dent Pract 2015;16(1):1-6.

The aim of this study was to judge the reliability of evaluating thyroid-stimulating hormone (TSH) and free thyroxine (f-T4) in the morning and afternoon in differentiated thyroid carcinoma (DTC) patients. We evaluated 153 DTC patients, aged 61 ± 13 years, in active follow-up in our center after primary treatments and under stabilized levo-thyroxine (L-T4) posology. In each patient, morning and afternoon examinations were performed 1-3 months apart. Blood samples were collected at 08:00–09:00 h and 15:00–16:00 h. TSH and f-T4 were evaluated in both samples. Thyroglobulin (Tg), Tg-antibodies and neck ultrasonography were also evaluated. According to clinical and laboratory examinations, 92% of patients were disease-free, 6% had biochemical disease, and 2% structural disease. L-T4 dosages (1.64 ± 0.38 µg/kg b.w.) proved the same on both occasions, despite slight changes in body weight or L-T4 posology in 15% of patients. Free-T4 values were significantly higher in the afternoon (21.5 ± 0.3 pmol/L) than in the morning (18.8 ± 0.4 pmol/L; P

This work deals on the optimization and computational material design using the topological derivative concept. The necessary details to obtain the anisotropic topological derivative are first presented. In the context of multi-scale topology optimization, it is crucial since the homogenization of the constitutive tensor of a micro-structure confers in general an anisotropic response. In addition, this work addresses the multi-scale material design problem in which the goal is then to minimize the structural (macro-scale) compliance by appropriately designing the material distribution (micro-structure) at a lower scale (micro-scale). To overcome the exorbitant computational cost, a consultation during the iterative process of a discrete material catalog (computed off-line) of micro-scale optimized topologies (Computational Vademecum) is proposed in this work. This results into a large diminution of the resulting computational costs, which make affordable the proposed methodology for multi-scale computational material design. Some representative examples assess the performance of the considered approach.

The paper deals with topology design of thermomechanical actuators. The goal of shape optimization is to maximize the output displacement in a given direction on the boundary of the elastic body, which is submitted to a thermal excitation that induces a dilatation/contraction of the thermomechanical device. The optimal structure is identified by an elastic material distribution, while a very compliant (weak) material is used to mimic voids. The mathematical model of an actuator takes the form of a semi-coupled system of partial differential equations. The boundary value problem includes two components, the Navier equation for linear elasticity coupled with the Poisson equation for steady-state heat conduction. The mechanical coupling is the thermal stress induced by the temperature field. Given the integral shape functional, we evaluate its topological derivative with respect to the nucleation of a small circular inclusion with the thermomechanical properties governed by two contrast parameters. The obtained topological derivative is employed to generate a steepest descent direction within the level set numerical procedure of topology optimization in a fixed geometrical domain. Finally, several finite element-based examples for the topology design of thermomechanical actuators are presented. Fil: Giusti, Sebastian Miguel. Universidad Tecnológica Nacional. Facultad Regional Córdoba. Departamento de Ingeniería Civil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina Fil: Mróz, Z.. Institute Of Fundamental Technological Research Of The Polish Academy Of Sciences; Polonia Fil: Novotny, Andrea Natalia. Laboratorio Nacional de Computacao Cientifica; Brasil Fil: Sokolowski, J.. Institute Of Fundamental Technological Research Of The Polish Academy Of Sciences; Polonia. Université de Lorraine; Francia

A numerical approach based on a computational constitutive multi-scale model is used in this work to predict the effective Young’s modulus and Poisson’s ratio of a pearlitic nodular cast iron. The Representative Volume Element (RVE) is defined based on a set of micrographs acquired from an optical device. For each micrograph, two RVE with different shape, rectangular and hexagonal, are defined. The volume fraction of graphite and metal matrix and the boundary of each object were identified on each RVE by using a procedure of image enhanced and segmentation. The set of RVE obtained was meshed with triangular finite elements. The numerical results obtained with rectangular and hexagonal RVE are compared with results obtained by means of an analytical expression. The influence of graphite fractions, aspect ratios and nodularity are investigated. The results show that graphite fraction has the largest influence on the effective modulus E. This feature is independent of the external shape of the RVE. Only one multi-scale model show a good agreement with the analytical expression in the effective modulus E. Also, the influence of the graphite volume fraction on the effective Poisson’s ratio is investigated by means of multi-scale simulation. Fil: Carazo, Fernando Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Mecanica Aplicada; Argentina Fil: Giusti, Sebastian Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Tecnológica Nacional. Facultad Regional Córdoba. Departamento de Ingeniería Civil; Argentina Fil: Boccardo, Adrian Dante. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Tecnológica Nacional. Facultad Regional Córdoba. Departamento de Ingeniería Civil; Argentina Fil: Godoy, Luis Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina

This is the accepted version of the following article: Toro, S., Sanchez, P.J., Huespe, A.E., Giusti, S.M., Blanco, P.J. and Feijoo, R.A. (2014), A two-scale failure model for heterogeneous materials: numerical implementation based on the finite element method. Int. J. Numer. Meth. Engng., 97: 313–351. doi: 10.1002/nme.4576, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/nme.4576/abstract

Summary Background The photodynamic therapy (PDT) involves the use of light of specific wavelength to activate a nontoxic photosensitizing agent or dye in the presence of oxygen for eradication of target cells. In dentistry, this therapy is used to suppress the growth of microorganisms involved directly with dental decay and periodontitis process. There are evidences that curcumin dye is able to control microbial activity when illuminated with specific wavelength. The purpose of this study was to evaluate the in vitro efficacy of PDT using curcumin dye (Cur-C) in combination with a blue LED (L) device on a planktonic model of Streptococcus mutans ( S. mutans ). Methods Suspensions (0.5 mL) containing S. mutans at 1 × 10 7 CFU mL −1 were prepared and divided into 4 groups: Group C − L− (control: no treatment and 1 experimental condition), Group C + L− (curcumin at 3 different concentrations: 2000; 4000 and 8000 μM and 3 experimental conditions), Group C − L+ (LED at 3 different dosages: 24, 48 and 72 J cm −2 and 3 experimental conditions), and Group C + L+ (PDT group: curcumin at respective concentrations combined to LED dosages and 9 experimental conditions). Samples of each experimental condition were cultured in Petri dishes of BHI agar. Incubation in micro-aerophilia at 37 °C for 48 h was performed for subsequent visual counting of CFU/mL. Data were transformed into log 10 and analyzed by two-way ANOVA and Tukey's test at p Results Group C + L+, in specific experimental conditions, demonstrated a log bacterial reduction 70% higher than Group C − L−. Both groups C − L+ and C + L− presented a slight decrease in log bacterial counting. Conclusion This in vitro method was able to reduce the number of S. mutans in a planktonic suspension.

A cohesive zone model implemented in an augmented Lagrangian functional is used for simulation of meso-scale fracture problems in this paper. The method originally developed by Lorentz is first presented in a rigorous variational framework. The equivalence between the stationary point of the one-field problem and the saddle point of the mixed formulation is proved by solving the double inequality of the mixed functional. An adaptation to simulate fracture phenomena in the meso-scale via mesh modification is also presented as an algorithm to insert zero-thickness interface elements based on Lagrange multipliers, boarding the non-trivial task of the field interpolation for different crack paths (plain and tortuous). A suitable tool to study the matrix fracture and debonding phenomena in composites with strongly different component stiffnesses that avoids ill-conditioning matrices associated with intrinsic cohesive zone models is obtained. The method stability is discussed using a simple patch test. Some numerical applications to fracture problems taking into account the mesostructure and, particularly, the study of transverse failure of longitudinal fiber reinforced epoxy and the fracture in concrete specimens are included in the paper. Comparing the numerical results with the experimental results obtained by other researchers, the paper introduces a discussion about the influence of coarse aggregate volume in meso-scale fracture mechanisms in concrete L-shaped specimens. Fil: Labanda, Nicolás Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Instituto de Estructuras "Ing. Arturo M. Guzmán"; Argentina Fil: Giusti, Sebastian Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Tecnológica Nacional. Facultad Regional Córdoba. Departamento de Ingeniería Civil; Argentina Fil: Luccioni, Bibiana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Instituto de Estructuras "Ing. Arturo M. Guzmán"; Argentina

Made available in DSpace on 2018-12-11T17:04:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-05-20 Antimicrobial photodynamic therapy (aPDT) is increasingly being explored for treatment of periodontitis. Here, we investigated the effect of aPDT on human dental plaque bacteria in suspensions and biofilms in vitro using methylene blue (MB)-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles (MB-NP) and red light at 660 nm. The effect of MB-NP-based aPDT was also evaluated in a clinical pilot study with 10 adult human subjects with chronic periodontitis. Dental plaque samples from human subjects were exposed to aPDT—in planktonic and biofilm phases—with MB or MB-NP (25 μ/mL) at 20 J/cm2 in vitro. Patients were treated either with ultrasonic scaling and scaling and root planing (US + SRP) or ultrasonic scaling + SRP + aPDT with MB-NP (25 μ/mL and 20 J/cm2) in a split-mouth design. In biofilms, MB-NP eliminated approximately 25% more bacteria than free MB. The clinical study demonstrated the safety of aPDT. Both groups showed similar improvements of clinical parameters one month following treatments. However, at three months ultrasonic SRP + aPDT showed a greater effect (28.82%) on gingival bleeding index (GBI) compared to ultrasonic SRP. The utilization of PLGA nanoparticles encapsulated with MB may be a promising adjunct in antimicrobial periodontal treatment. Faculdade de Ciencias Farmaceuticas UNESP—Univ Estadual Paulista Departamento de Análises Clínicas, Campus Araraquara Faculdade de Ciencias Farmaceuticas UNESP—Univ Estadual Paulista Departamento de Farmacos e Medicamentos, Campus Araraquara Instituto de Fisica de Sao Carlos Universidade de Sao Paulo, Caixa Postal 369 Applied Molecular Photomedicine Laboratory The Forsyth Institute, 245 First Street Department of PharmaceuticalSciences School of Pharmacy Bouvé College of Health Sciences Northeastern University, 140 The Fenway, Room 156, 360 Huntington Avenue Faculdade de Ciencias Farmaceuticas UNESP—Univ Estadual Paulista Departamento de Análises Clínicas, Campus Araraquara Faculdade de Ciencias Farmaceuticas UNESP—Univ Estadual Paulista Departamento de Farmacos e Medicamentos, Campus Araraquara

In 2008 AGILE and Fermi detected gamma-ray flaring activity from the unidentified EGRET source 3EG J1236+0457, recently associated with a flat spectrum radio quasar GB6 J1239+0443 at z=1.762. The optical counterpart of the gamma-ray source underwent a flux enhancement of a factor 15-30 in 6 years, and of ~10 in six months. We interpret this flare-up in terms of a transition from an accretion-disk dominated emission to a synchrotron-jet dominated one. We analysed a Sloan Digital Sky Survey (SDSS) archival optical spectrum taken during a period of low radio and optical activity of the source. We estimated the mass of the central black hole using the width of the CIV emission line. In our work, we have also investigated SDSS archival optical photometric data and UV GALEX observations to estimate the thermal-disk emission contribution of GB6 J1239+0443. Our analysis of the gamma-ray data taken during the flaring episodes indicates a flat gamma-ray spectrum, with an extension of up to 15 GeV, with no statistically-relevant sign of absorption from the broad line region, suggesting that the blazar-zone is located beyond the broad line region. This result is confirmed by the modeling of the broad-band spectral energy distribution (well constrained by the available multiwavelength data) of the flaring activity periods and by the accretion disk luminosity and black hole mass estimated by us using archival data.

This paper proposes an algorithm for the synthesis/optimization of microstructures based on an exact formula for the topological derivative of the macroscopic elasticity tensor and a level set domain representation. The macroscopic elasticity tensor is estimated by a standard multi-scale constitutive theory where the strain and stress tensors are volume averages of their microscopic counterparts over a representative volume element. The algorithm is of simple computational implementation. In particular, it does not require artificial algorithmic parameters or strategies. This is in sharp contrast with existing microstructural optimization procedures and follows as a natural consequence of the use of the topological derivative concept. This concept provides the correct mathematical framework to treat topology changes such as those characterizing microstuctural optimization problems. The effectiveness of the proposed methodology is illustrated in a set of finite element-based numerical examples.Copyright © 2010 John Wiley & Sons, Ltd.

This study provides the first report that Sphagnum centrale and S. henryense are allopolyploids. Microsatellites show S. henryense and S. palustre to be conspecific. In contrast, they show S. centrale to be genetically distinct from S. palustre s.l. In addition to differences in alleles and allele frequencies, the patterns of observed heterozygosity across 17 microsatellite markers also differed between S. centrale and S. palustre s.l. This represents a dimension of genetic differentiation that is not detected or addressed by statistical approaches such as AMOVA or Principal Coordinates Analysis. The patterns of microsatellites further provide preliminary evidence suggesting that S. centrale and S. palustre have one parental taxon in common and differ in the second.

This paper proposes an exact analytical formula for the topological sensitivity of the macroscopic response of elastic microstructures to the insertion of circular inclusions. The macroscopic response is assumed to be predicted by a well-established multi-scale constitutive theory where the macroscopic strain and stress tensors are defined as volume averages of their microscopic counterpart fields over a representative volume element (RVE) of material. The proposed formula—a symmetric fourth-order tensor field over the RVE domain—is a topological derivative which measures how the macroscopic elasticity tensor changes when an infinitesimal circular elastic inclusion is introduced within the RVE. In the limits, when the inclusion/matrix phase contrast ratio tends to zero and infinity, the sensitivities to the insertion of a hole and a rigid inclusion, respectively, are rigorously obtained. The derivation relies on the topological asymptotic analysis of the predicted macroscopic elasticity and is presented in detail. The derived fundamental formula is of interest to many areas of applied and computational mechanics. To illustrate its potential applicability, a simple finite element-based example is presented where the topological derivative information is used to automatically generate a bi-material microstructure to meet pre-specified macroscopic properties.

PurposeThe purpose of this paper is to assess the Gurson yield criterion for porous ductile metals.Design/methodology/approachA finite element procedure is used within a purely kinematical multi‐scale constitutive modelling framework to determine estimates of extremal overall yield surfaces. The RVEs analysed consist of an elastic‐perfectly plastic von Mises type matrix under plane strain conditions containing a single centered circular hole. Macroscopic yield surface estimates are obtained under three different RVE kinematical assumptions: linear boundary displacements (an upper bound); periodic boundary displacement fluctuations (corresponding to periodically perforated media); and, minimum constraint or uniform boundary traction (a lower bound).FindingsThe Gurson criterion predictions fall within the bounds obtained under relatively high void ratios – when the bounds lie farther apart. Under lower void ratios, when the bounds lie close together, the Gurson predictions of yield strength lie slightly above the computed upper bounds in regions of intermediate to high stress triaxiality. A modification to the original Gurson yield function is proposed that can capture the computed estimates under the three RVE kinematical constraints considered.Originality/valueAssesses the accuracy of the Gurson criterion by means of a fully computational multi‐scale approach to constitutive modelling. Provides an alternative criterion for porous plastic media which encompasses the common microscopic kinematical constraints adopted in this context.

On September 27, 2006, the U.S. Food and Drug Administration granted accelerated approval to panitumumab (Vectibix™; Amgen, Inc., Thousand Oaks, CA) for the treatment of patients with epidermal growth factor receptor–expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Accelerated approval was based on demonstration of a beneficial effect on progression-free survival (PFS). The present submission summarizes a second clinical trial, to be included in the panitumumab package insert in June 2008, of chemotherapy and bevacizumab with and without panitumumab in the first-line treatment of patients with metastatic colorectal cancer. The study was closed when inferior PFS and greater toxicity were demonstrated at the time of the planned interim efficacy analysis. Patients receiving panitumumab in combination with bevacizumab and chemotherapy experienced a higher incidence of death (9% versus 4%) and a higher risk for grade 3 and 4 toxicities than patients receiving bevacizumab and chemotherapy alone. The incidences of any Common Terminology Criteria for Adverse Events grade 3 and 4 adverse events (AEs) were 87% and 72% in the panitumumab and control groups, respectively. Grade 3 and 4 AEs occurring more commonly in panitumumab-treated patients included rash/acneiform dermatitis, diarrhea, dehydration, primarily resulting from diarrhea, hypokalemia, stomatitis/mucositis, and pulmonary embolism. The addition of panitumumab to bevacizumab and chemotherapy for the first-line treatment of metastatic colorectal cancer was harmful when compared with bevacizumab and chemotherapy alone. The use of panitumumab in this setting cannot be recommended.

The aim of this work is to present the calculation of the topological derivative for the total potential energy associated to the steady-state orthotropic heat diffusion problem, when a circular inclusion is introduced at an arbitrary point of the domain. By a simple change of variables and using the first order Polya-Szego polarization tensor, we obtain a closed formula for the topological sensitivity. For the sake of completeness, the analytical expression for the topological derivative is checked numerically using the standard Finite Element Method. Finally, we present two numerical experiments showing the influency of the orthotropy in the topological derivative field and also one example concerning the optimal design of a heat conductor.

This paper proposes a closed form expression for the sensitivity of the macroscopic heat conductivity tensor for two-dimensional problems to topological microstructural changes of the underlying material. The sensitivity formula is remarkably simple. It is derived by applying the concept of topological derivative within a variational multi-scale framework for steady-state heat conduction where the macroscopic temperature gradient and heat flux are defined as volume averages of their microscopic counterparts over a representative volume element (RVE) of material. The classical Fourier law is assumed to hold at the scale referred to as microscopic (the RVE). The derived sensitivity – a symmetric second order tensor field over the RVE domain – measures how the estimated macroscopic conductivity tensor changes when a small circular inclusion is introduced at the micro-scale. The proposed formula finds potential application in the design and optimisation of heat conducting materials.

International audience; In control of distributed parameter systems the piezoelectric actuators are of com-mon use. The topology optimization of a multiphysic model in piezoelectricity is considered. The topological derivative of a tracking-type shape functional is derived in its closed form for the pur-pose of shape optimization of piezoelectric actuators. The optimum design procedure is applied to a micromechanism which transforms the electrical energy supplemented via its piezoceramic part into elastic energy of an actuator. The domain decomposition technique and the Steklov-Poincaré pseudo-differential boundary operator are employed in the asymptotic analysis of the shape func-tional defined on a part of the boundary of the elastic body under consideration. The proposed method of sensitivity analysis is general and can be used for the purpose of the shape-topological optimization for a broad class of multiphysics models. The numerical results confirm the efficiency of proposed approach to optimum design in multiphysics. 1. Introduction . In this paper we are interested in the optimal design of piezo-electric actuators, which consist of multi-flexible structures actuated by piezoceramic devices that generate an output displacement in a specified direction on the boundary of the actuated part [5, 27]. The multi-flexible structure transforms the piezoceramic output displacement by amplifying and changing its direction. This kind of mecha-nism can be manufactured at a very small scale. Therefore, the spectrum of appli-cations of such microtools becomes broader in recent years including microsurgery, nanotechnology processing, cell manipulation, among others. Yet, the development of microtools requires the design of actuated multi-flexible structures which are able to produce complex movements originated from simple expansion/contraction of the piezoceramic actuator. The performance of microtools can be strongly enhanced by optimizing the actuated multi-flexible structures with respect to their shape and their topology [6, 7, 8]. The shape sensitivity analysis of such coupled models has been fully developed in [19] and [18] for quasi-electrostatic layered piezoelectric devices and for non-stationary elastic, piezoelectric and acoustic coupled system, respectively. For the mathematical theory concerning coupled PDEs systems the reader may refer to e.g., [17, 20, 21]. However, a more general approach to deal with shape and topology optimization design is based on the topological derivative. In fact, this relatively new concept