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Probabilistic domain decomposition (PDD) is an alternative paradigm for solving boundary value problems (BVPs) in parallel with excellent scalability properties, thanks to its reliance on stochastic representations of the BVP. However, there are cases when the latter is less numerically convenient, or unknown. Semilinear elliptic BVPs and the Helmholtz equation are prominent examples of either class. In this paper, we overcome this issue by designing suitable iterative schemes for either problem. These schemes not only retain the desirable properties of PDD but also are optimally suited for pathwise variance reduction, resulting in a systematic, nearly cost-free reduction of the statistical error through the iterations. Numerical tests carried out on the supercomputer Marconi100 are presented. [ABSTRACT FROM AUTHOR]

Background and objective. Scar contractures in the hand are a sequela of burns that can lead to functional impairment. The perforator flap from the digital artery, taken from the lateral aspect of the fingers, represents an excellent therapeutic option for managing these injuries. We present our experience with this surgical technique and our morphological and functional results. Methods. We present our experience with 14 flaps in 7 patients affected by web contractures in the hand. These flaps, based on perforators from the digital artery, use the adjacent lateral aspect of the proximal phalanx as the donor site. The donor area was covered with full-thickness skin grafts. Patients underwent early rehabilitation, pressure therapy, and nighttime splinting. Results. The survival of the flaps was successful in all 14 cases. One case experienced graft necrosis in the donor site of the flap, which resolved with conservative treatment. Commissural contractures were resolved in 85.7% of the cases (13 out of 14 cases). The mean follow-up period was 27.3 months (range 12-45 months). In 1 case, partial recurrence occurred at 10 months and it was successfully managed with Z-plasty. Patients reported subjective improvement in hand functionality and aesthetics. The interdigital space angle, measured in degrees, improved from a mean of 22.5 degrees preoperatively (range 15°-35°) to a mean of 36.8 degrees postoperatively (range 25°-45°). Conclusions. In our experience, the perforator flap from the digital artery represents a rapid, straightforward, and effective therapeutic option for treating contractures after burns in the second to fourth interdigital spaces. Adequate postoperative care, rehabilitation, pressure therapy and splinting are essential for optimal outcomes. [ABSTRACT FROM AUTHOR]

A methodology is presented for the numerical solution of nonlinear elliptic systems in unbounded domains, consisting of three elements. First, the problem is posed on a finite domain by means of a proper nonlinear change of variables. The compressed domain is then discretised, regardless of its final shape, via the radial basis function partition of unity method. Finally, the system of nonlinear algebraic collocation equations is solved with the trust-region algorithm, taking advantage of analytically derived Jacobians. We validate the methodology on a benchmark of computational fluid mechanics: the steady viscous flow past a circular cylinder. The resulting flow characteristics compare very well with the literature. Then, we stress-test the methodology on less smooth obstacles—rounded and sharp square cylinders. As expected, in the latter scenario the solution is polluted by spurious oscillations, owing to the presence of boundary singularities. • Infinite domain compression removes the need for artificial computational domain and the hard-to-quantify associated error. • Nonlinear elliptic PDEs, particularly systems thereof, are very rare in the RBF literature. • RBF-PU allows for handling systems of nonlinear PDEs in strong form on irregular domains without loss of performance. • RBF-PU's accurate derivates lead to a compact, sparse, easy-to-derive analytical Jacobian. • Detailed transition from circular to square cylinder investigated numerically, showing good agreement with published results. [ABSTRACT FROM AUTHOR]

This research seeks to identify necessary elements that allow students to improve self-regulation of learning and self-efficacy in their results in order to achieve a thorough education based on the experience of undergraduate users with their virtual platform. A quantitative method was used, involving a survey questionnaire which would subtract the objective aspects of data collection. The sample was determined according to simple random sampling. As part of the research, the perceptions of students and professors was analyzed, inquiring them on their levels of selfregulation and self-efficacy. Considering the results, the appreciation of the platform was positive while opinions were divided as for the levels of selfregulation and their conception of self-efficiency. [ABSTRACT FROM AUTHOR]

Non-Governmental Organizations (NGO) aim to provide basic goods and health care to people affected by human and natural disasters or by situations of extreme poverty. With this objective, collaboration took place between the Spanish Society os Plastic, Reconstructive and Aesthetic Surgery (SECPRE) and the order of the Brothers of San Juan de Dios. One of its achievements has been that this campaign has taken place for the second consecutive year at Saint Joseph's Catholic Hospital in Monrovia (Liberia). In this article, we describe our personal experience during the humanitarian project carried out in November 2017. We intend to communicate not only the working conditions, but also the personal experience of all the team members involved, with the aim of supporting future campaigns. [ABSTRACT FROM AUTHOR]

The numerical solution of large-scale PDEs, such as those occurring in data-driven applications, unavoidably require powerful parallel computers and tailored parallel algorithms to make the best possible use of them. In fact, considerations about the parallelization and scalability of realistic problems are often critical enough to warrant acknowledgement in the modelling phase. The purpose of this paper is to spread awareness of the Probabilistic Domain Decomposition (PDD) method, a fresh approach to the parallelization of PDEs with excellent scalability properties. The idea exploits the stochastic representation of the PDE and its approximation via Monte Carlo in combination with deterministic high-performance PDE solvers. We describe the ingredients of PDD and its applicability in the scope of data science. In particular, we highlight recent advances in stochastic representations for non-linear PDEs using branching diffusions, which have significantly broadened the scope of PDD. We envision this work as a dictionary giving large-scale PDE practitioners references on the very latest algorithms and techniques of a non-standard, yet highly parallelizable, methodology at the interface of deterministic and probabilistic numerical methods. We close this work with an invitation to the fully non-linear case and open research questions. [ABSTRACT FROM PUBLISHER]

Background and Objective. Osteoarthritis of the thumb carpometacarpal (CMC) joint remains one of the main reasons for visiting a Hand Centre. Whenever the conservative treatment fails, the surgical approach will be offered. This treatment should be indicated individually for each patient, depending on various factors as the age, the degeneration degree, the functional demand and so on. In this paper the author analyse the outcomes of different techniques, based on his own surgical experience. Methods. Between April 2011 and February 2015, 97 cases of thumb arthritis have been treated surgically. The average age of the patients was 54.01 years, with predominance of females (85.5 %). The most frequently used technique was the ligament reconstruction tendon interposition technique, as Weilby's recomends with 79 cases. In 9 cases an arthroscopic arthroplasty was performed (ATK); in 4 patients a CMC fusion; and in 5 a ligamentoplasty. Results. Out of the 97 patients, 49 have been controlled with an average follow up of 18.3 months. Patients referred an improvement in pinch strength of 24.28% in theWeilby's technique group; 18.74% in the ATK group; 45.75 % in the CMC fusion group; and 31.42 % in the ligamentoplasty group. Focus on the pain, assessed by the visual analog scale, the improvement was 5.50, 5.1, 6.34 and 6.33 points respectively, compared to the preoperative situation. Conclusions. These outcomes confirm the usefulness of the suspension - interposition arthroplasty as an ideal technique for the common patient of rizarthrosis. In some cases, some factors such as age, functional demand or the degree of joint degeneration, lead us to look for other techniques in order to satisfy needs patient's request. [ABSTRACT FROM AUTHOR]

This work is concerned with the excited state quantum phase transitions (ESQPTs) defined in Ann. Phys. 323, 1106 (2008). In many-body models that exhibit such transitions, the ground state quantum phase transition (QPT) occurs in parallel with a singularity in the energy spectrum that propagates to higher energies as the control parameter increases beyond the QPT critical point. The analysis of the spectrum has been a main tool for the detection of these ESQPTs. Studies of the effects of this transition on the system dynamics are more limited. Here, we extend our previous works and show that the evolution of an initial state with energy close to the ESQPT critical point may be extremely slow. This result is surprising, because it may take place in systems with long-range interactions, where the dynamics is usually expected to be very fast. A timely example is the one-dimensional spin-1/2 model with infinite-range Ising interaction studied in experiments with ion traps. Its Hamiltonian has a U(2) algebraic structure. More generally, the slow dynamics described here occurs in two-level bosonic or fermionic models with pairing interactions and a [ABSTRACT FROM AUTHOR]

We present an iterative scheme, reminiscent of the Multigrid method, to solve large boundary value problems with Probabilistic Domain Decomposition (PDD). In it, increasingly accurate approximations to the solution are used as control variates in order to reduce the Monte Carlo error of the following iterates—resulting in an overall acceleration of PDD for a given error tolerance. The key feature of the proposed algorithm is the ability to approximately predict the speedup with little computational overhead and in parallel. Besides, the theoretical framework allows to explore other aspects of PDD, such as stability. One numerical example is worked out, yielding an improvement between one and two orders of magnitude over the previous version of PDD. [ABSTRACT FROM AUTHOR]

We consider the numerical solution of nonlinear elliptic boundary value problems with Kansa’s method. We derive analytic formulas for the Jacobian and Hessian of the resulting nonlinear collocation system and exploit them within the framework of the trust-region algorithm. This ansatz is tested on semilinear, quasilinear and fully nonlinear elliptic PDEs (including Plateau’s problem, Hele–Shaw flow and the Monge–Ampère equation) with excellent results. The new approach distinctly outperforms previous ones based on linearization or finite-difference Jacobians. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effect of ractopamine intake at concentrations of 0 ppm (control), 10 ppm, 20 ppm and 40 ppm in the diet on the physiological and immunological parameters, through the analysis of hematological parameters and serum concentration of cortisol and lactate in 80 Nile tilapia (Oreochromis niloticus) of the GIFT strain, weighing 500 grams, randomly distributed in 16 water tanks with a capacity of 500 liters, with the density of 5 animals. Withdrawing from day 0 to 1 animal in each box, and every 20 days, 2 fish per box, totaling eight fish each treatment. They were collected blood samples for cortisol assay, lactate and haematological parameters (red blood cell count, white blood cells, total protein - PPT, packed cell volume. - VG, hemoglobin, lactate showed a significant decrease (p <0.05) at both times collection with 10 ppm (3.79 mmol / L to 20 days and 1.58 mmol / L at 40 days) and compared with the control (4.61 mmol / L at day 0, 4.78 mmol / L to 20 4.54 days and 40 days) and the same concentration differed compared with 40 ppm of ractopamine at 40 days (3.15 mmol / L) The parameters evaluated, cortisol, blood counts, white blood cells, packed cell volume. - VG, hemoglobin, showed no significant difference (p <0.05) between treatments and collection times. The results of this study did not demonstrate a physiological stress produced by ractopamine intake in concentrations of 10, 20 and 40 ppm for animals. However, more studies on the subject should be carried out so that the additive use is recommended securely on the welfare of fish. [ABSTRACT FROM AUTHOR]

ATP, one of the signaling molecules most commonly secreted in the nervous system and capable of stimulating multiple pathways, binds to the ionotropic purinergic receptors, in particular, the P2X7 receptor (P2X7R) and stimulates neuronal cell death. Given this effect of purinergic receptors on the viability of dopaminergic neurons model cells and that Ras GTPases control Erk1/2-regulated mitogen-activated cell proliferation and survival, we have investigated the role of the small GTPases of the Ras superfamily, together with their regulatory and effector molecules as the potential molecular intermediates in the P2X7R-regulated cell death of SN4741 dopaminergic neurons model cells. Here, we demonstrate that the neuronal response to purinergic stimulation involves the Calmodulin/RasGRF1 activation of the small GTPase Ras and Erk1/2. We also demonstrate that tyrosine phosphatase PTPRβ and other tyrosine phosphatases regulate the small GTPase activation pathway and neuronal viability. Our work expands the knowledge on the intracellular responses of dopaminergic cells by identifying new participating molecules and signaling pathways. In this sense, the study of the molecular circuitry of these neurons is key to understanding the functional effects of ATP, as well as considering the importance of these cells in Parkinson's Disease. [ABSTRACT FROM AUTHOR]

• Modeling of the experimental bending rovibrational spectra data of a set of molecular species which encompasses the full gamut of structures: semirigid linear (HNC), semirigid bent (H2S) and nonrigid (Si2C and NCNCS). • Most general Hamiltonian of the two dimensional limit of the vibron model including all possible interactions up to four-body. • Predictions of the higher excited rovibrational energies are provided. • Analysis of the molecular dynamical structure using the quantum monodromy diagram, the Birge-Sponer plot and the participation ratio. We present an extension of the Hamiltonian of the two dimensional limit of the vibron model to encompass all possible interactions up to four-body operators. We apply this Hamiltonian to the modeling of the bending spectrum of four molecules: HNC, H 2 S, Si 2 C, and NCNCS. The selected molecular species include linear, bent, and nonrigid equilibrium structures, proving the versatility of the algebraic approach which allows for the consideration of utterly different physical cases within a single Hamiltonian and a general formalism. For each case we compute predicted bending energies and wave functions, that we use to depict the associated quantum monodromy diagram, Birge-Sponer plot, and participation ratio. In nonrigid cases, we also show the bending energy functional obtained using the coherent –or intrinsic– state formalism. [ABSTRACT FROM AUTHOR]

Social and affective relations occur at every stage of our lives. Impairments in the quality of this "social world" can be exceptionally detrimental and lead to psychopathology or pathological behavior, including schizophrenia, autism spectrum disorder, affective disorders, social phobia or violence, among other things. Exposure to highly stressful or traumatic events, depending on the stage of life in which stress exposure occurs, could severely affect limbic structures, including the amygdala, and lead to alterations in social and affective behaviors. This review summarizes recent findings from stress research and provides an overview of its age-dependent effects on the structure and function of the amygdala, which includes molecular and cellular changes, and how they can trigger deviant social and affective behaviors. It is important to highlight that discoveries in this field may represent a breakthrough both for medical science and for society, as they may help in the development of new therapeutic approaches and prevention strategies in neuropsychiatric disorders and pathological behaviors. [ABSTRACT FROM AUTHOR]

The signaling pathway of the microtubule-associated protein kinase or extracellular regulated kinase (MAPK/ERK) is a common mechanism of extracellular information transduction from extracellular stimuli to the intracellular space. The transduction of information leads to changes in the ongoing metabolic pathways and the modification of gene expression patterns. In the central nervous system, ERK is expressed ubiquitously, both temporally and spatially. As for the temporal ubiquity, this signaling system participates in three key moments: (i) Embryonic development; (ii) the early postnatal period; and iii) adulthood. During embryonic development, the system is partly responsible for the patterning of segmentation in the encephalic vesicle through the FGF8-ERK pathway. In addition, during this period, ERK directs neurogenesis migration and the final fate of neural progenitors. During the early postnatal period, ERK participates in the maturation process of dendritic trees and synaptogenesis. During adulthood, ERK participates in social and emotional behavior and memory processes, including long-term potentiation. Alterations in mechanisms related to ERK are associated with different pathological outcomes. Genetic alterations in any component of the ERK pathway result in pathologies associated with neural crest derivatives and mental dysfunctions associated with autism spectrum disorders. The MAP-ERK pathway is a key element of the neuroinflammatory pathway triggered by glial cells during the development of neurodegenerative diseases, such as Parkinson's and Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis, as well as prionic diseases. The process triggered by MAPK/ERK activation depends on the stage of development (mature or senescence), the type of cellular element in which the pathway is activated, and the anatomic neural structure. However, extensive gaps exist with regards to the targets of the phosphorylated ERK in many of these processes. [ABSTRACT FROM AUTHOR]

We present an accurate simulation of the Raman spectrum of the carbon dioxide molecule in the 1150–1500 cm−1 spectral range, comparing the results obtained using the three polyad schemes found in the literature of this molecule. The description of the molecule with the algebraic U1(2)×U(3)×U2(2) local model encompasses both stretching and bending degrees of freedom. A detailed analysis of the Hamiltonian interactions for the three polyad schemes provides fittings with root mean square deviations in the range 0.14–0.20 cm−1, involving 19 parameters taking into account the 178 experimental term energies found in the literature. Using a limited subset of 9 experimental transition moments, we optimize 5 partial derivatives of the mean polarizability and simulate the Raman spectrum of CO2 for the three polyad schemes. Comparing the calculated results with the experimental spectrum, we obtain an overall good agreement for the three polyads. However, an inspection in detail of the spectrum seems to show a slight preference for polyad P212 albeit not due to the interaction characterizing the polyad but due to anharmonic effects and energy distribution. Finally, we assess the effect of the Fermi resonance over CO2 Raman line intensities. [ABSTRACT FROM AUTHOR]

Purpose: This paper aims to provide a strategic analysis of firms at the lowest hierarchical levels of the defence industry. Design/methodology/approach: This paper presents the main results of an exploratory, multiple-case study that analyses the current strategy drivers and their views about the future ones, and their impact at the lowest hierarchical levels of the defence industry in Spain. Findings: This investigation develops and analyses a contingency model regarding the strategy impact and effects of firms' drivers and clients, both mediated by the strategy players because of their huge impact on the defence industry. The research model focuses on the internal relations between technical and commercial activities due to the cause and effect of their capabilities. Simultaneously, pull and push mechanisms boost firms' capabilities and requirements to provide strategic foresight. Practical implications: Ministries of Defence (MoDs) and prime contractors will remain mediating players in the near future even with further implications for the competition of Defence Technological and Industrial Base (DTIB) firms. It implies that firms and MoDs must maintain a close relation and implement more flexible practices, such as open innovation, property rights or new commercialization schemes. Originality/value: This study offers insights related to the specific applications and the necessity of commercial and technological areas alignment of these firms for the future. [ABSTRACT FROM AUTHOR]

Summary: The nucleus incertus (NI) in the pontine tegmentum sends ascending projections to the midbrain, hypothalamus, amygdala, basal forebrain, hippocampus, and prefrontal cortex, and has a postulated role in modulating several forebrain functions. A substantial population of GABAergic NI neurons expresses the neuropeptide, relaxin‐3, which acts via the Gi/o‐protein‐coupled receptor, RXFP3, present throughout the forebrain target regions. Broad and specific manipulations of these systems by activation or inhibition of the NI or modulating RXFP3 signaling have revealed key insights into the likely influence of the NI/relaxin‐3/RXFP3 system on modalities including arousal, feeding, stress responses, anxiety and addiction, and attention and memory. This range of actions corresponds to a likely impact of NI/(relaxin‐3) projections on multiple integrated circuits, but makes it difficult to draw conclusions about a generalized function for this network. This review will focus on the key physiological process of oscillatory theta rhythm and the neural circuits that promote it during behavioral activation, highlighting the ability of NI and relaxin‐3/RXFP3 signaling systems to modulate these circuits. A better understanding of these mechanisms may provide a way to therapeutically adjust malfunction of forebrain activity present in several pathological conditions. [ABSTRACT FROM AUTHOR]

Nucleus incertus (NI) neurons in the pontine tegmentum give rise to ascending forebrain projections and express the neuropeptide relaxin-3 (RLN3) which acts via the relaxin-family peptide 3 receptor (RXFP3). Activity in the hippocampus and entorhinal cortex can be driven from the medial septum (MS), and the NI projects to all these centers, where a prominent pattern of activity is theta rhythm, which is related to spatial memory processing. Therefore, we examined the degree of collateralization of NI projections to the MS and the medial temporal lobe (MTL), comprising medial and lateral entorhinal cortex (MEnt, LEnt) and dentate gyrus (DG), and the ability of the MS to drive entorhinal theta in the adult rat. We injected fluorogold and cholera toxin-B into the MS septum and either MEnt, LEnt or DG, to determine the percentage of retrogradely labeled neurons in the NI projecting to both or single targets, and the relative proportion of these neurons that were RLN3-positive (+). The projection to the MS was threefold stronger than that to the MTL. Moreover, a majority of NI neurons projected independently to either MS or the MTL. However, RLN3 + neurons collateralize significantly more than RLN3-negative (–) neurons. In in vivo studies, electrical stimulation of the NI induced theta activity in the MS and the entorhinal cortex, which was impaired by intraseptal infusion of an RXFP3 antagonist, R3(BΔ23-27)R/I5, particularly at ~ 20 min post-injection. These findings suggest that the MS plays an important relay function in the NI-induced generation of theta within the entorhinal cortex. [ABSTRACT FROM AUTHOR]

Background and Purpose: Pharmacological strategies aimed to facilitate neuronal renewal in the adult brain, by promoting endogenous neurogenesis, constitute promising therapeutic options for pathological or traumatic brain lesions. We have previously shown that non-tumour-promoting PKC-activating compounds (12-deoxyphorbols) promote adult neural progenitor cell (NPC) proliferation in vitro and in vivo, enhancing the endogenous neurogenic response of the brain to a traumatic injury. Here, we show for the first time that a diterpene with a lathyrane skeleton can also activate PKC and promote NPC proliferation.Experimental Approach: We isolated four lathyranes from the latex of Euphorbia plants and tested their effect on postnatal NPC proliferation, using neurosphere cultures. The bioactive lathyrane ELAC (3,12-di-O-acetyl-8-O-tigloilingol) was also injected into the ventricles of adult mice to analyse its effect on adult NPC proliferation in vivo.Key Results: The lathyrane ELAC activated PKC and significantly increased postnatal NPC proliferation in vitro, particularly in synergy with FGF2. In addition ELAC stimulated proliferation of NPC, specifically affecting undifferentiated transit amplifying cells. The proliferative effect of ELAC was reversed by either the classical/novel PKC inhibitor Gö6850 or the classical PKC inhibitor Gö6976, suggesting that NPC proliferation is promoted in response to activation of classical PKCs, particularly PKCß. ELAC slightly increased the proportion of NPC expressing Sox2. The effects of ELAC disappeared upon acetylation of its C7-hydroxyl group.Conclusions and Implications: We propose lathyranes like ELAC as new drug candidates to modulate adult neurogenesis through PKC activation. Functional and structural comparisons between ELAC and phorboids are included. [ABSTRACT FROM AUTHOR]

We present a polyad-preserving algebraic approach to molecular structure and, as an application, we fit the model parameters to reproduce an extensive experimental data set of vibrational energies of carbon dioxide in its ground electronic state. The data set includes levels with vibrational angular momentum ℓ = 1, ...,6 and some recently obtained term values that have not been previously considered. The obtained results are close to experimental uncertainty and we compare the results obtained making use of the three most common polyad schemes that can be found in the literature for this molecular species. Graphical abstract: [ABSTRACT FROM AUTHOR]

Introduction: Metabolic and inflammatory disorders are widely described in COVID-19 disease by SARS-CoV-2, especially in advanced gravity stages, nevertheless, the increase in inflammatory and tissue damage biomarkers could identify patients with higher mortality risk since early disease stages. Material and Method: A retrospective Cohort study was performed to evaluate the progression pattern and mortality risk of proinflammatory (Ferritin and IL- 6) and damage tissue biomarkers seric levels (LDH, CPK, CPK-MB and TnIc) since the beginning of the disease to end outcome considered, in this study, as death or recovery. Results: We evaluated 120 patients with mean age 51±10 years. The CAT study showed in all patients bilateral polished glass lung lesions. The inflammatory and seric tissue injured biomarkers were significantly higher since the beginning of the hospitalization in patients who died compared with patients that survived (p = 0.01). The myocardial injury biomarkers (CPK-MB and TnIc) were significantly higher in severe gravity stages of deceased patients compared to patients who survived (p = 0.001 and 0.003 respectively) with a global mortality of 38.3% (n = 48). The mortality risk was extremely elevated (RR> 10) when inflammatory and tissue injury biomarkers showed seric levels 2 folds above normal values, showing survival of < 60% after tenth day since the beginning disease. Conclusion: Since the beginning of COVID-19 disease by SARS CoV2 virus, patients show serum elevation in ferritin, LDH and CPK. This seric values were associated with higher mortality risk, when elevated 2 folds above normal values. [ABSTRACT FROM AUTHOR]

The goal of this research was to evaluate the microclimate (temperature, relative humidity and ECI–enthalpy comfort index) of commercial loads of broiler chickens at different transport distances: Dist15 (15 km on average) and Dist90 (90 km on average) in the summer and winter seasons and their effects on the production parameters body weight difference (BWD), mortality (%) and bruising prevalence (%). Twelve broiler loads were monitored using dataloggers to record temperature and humidity, with a total of 24 target crates per load. The experiment followed a factorial design [2 seasons (rainy and dry) × 2 distances (Dist15 and Dist90)] with a randomized complete block arrangement, 3 sexes (all males, all females, or mixed shipments) and one shipment per combination. BWD had a heterogeneous distribution throughout the load, and this distribution was not significantly correlated with the mean ECI measured during transport at 12 positions along the load. In terms of comfort, summer is the most critical period for broiler transport. In the interaction between rainy season and Dist90, the highest ECI was scored in the lethal zone (where physiological mechanisms are not enough to control body temperature). Mortality during the rainy season was not significantly different between distances. However, during the dry season, mortality was twice as high as broilers that travelled for 15 km. The prevalence of bruising on carcasses was not affected by the interaction between season and distance. As we know, broiler chicken performance, during transport, can be also related to road conditions, being hard to evaluate the real impact of seasons and distances on animal welfare. Load microclimate can compromise broiler chicken welfare during transport and it does not necessary reflect significant losses pre and post-slaughter. [ABSTRACT FROM AUTHOR]

Background: CIGB-247 is a cancer therapeutic vaccine that uses as antigen a variant of human vascular endothelial growth factor (VEGF) mixed with the bacterially-derived adjuvant VSSP. CIGB-247 has been already evaluated in two phase I clinical trials (CENTAURO and CENTAURO-2), showing to be safe and immunogenic in advanced cancer patients selected under well-defined and controlled clinical conditions. Surviving patients were submitted to monthly re-immunizations and some of them showed objective clinical benefits. Based on these results, a compassionate use program (CUP) with CIGB-247 was initiated for patients that did not meet the strict entry criteria applied for the CENTAURO and CENTAURO-2 clinical trials, but could potentially benefit from the application of this cancer therapeutic vaccine. Results: Polyclonal IgM, IgA and IgG antibodies specific for VEGF were detected by ELISA in serum samples from patients vaccinated with 400 μg of antigen combined with 200 μg of VSSP. Polyclonal antibody response showed no cross reactivity for other VEGF family member molecules like VEGF-C and VEGF-D. Serum from immunized individuals was able to block the binding of VEGF to its receptors VEGFR2 and VEGFR1. IgG fraction purified from immune sera shared the aforementioned characteristics and also inhibited the interaction between VEGF and the therapeutic recombinant antibody bevacizumab, an anti-angiogenic drug approved for the treatment of different tumors. No serious adverse events attributable to CIGB-247 have been documented yet in participants of the CIGB-247 CUP. The present paper is a first report of our findings concerning the humoral response and safety characteristics in treated CIGB-247 CUP cancer patients. The study has provided the unique opportunity of not only testing CIGB-247 in a broader clinical spectrum sample of Cuban cancer patients, but also within the context of the day-to-day clinical practice and treatment settings for these diseases in Cuban medical institutions. Conclusions: The CIGB-247 CUP has demonstrated that immunization and follow-up of a variety of cancer patients, under day-to-day clinical practice conditions in several Cuban medical institutions, replicate our previous findings in clinical trials: CIGB-247 is safe and immunogenic. [ABSTRACT FROM AUTHOR]

The present article has the purpose of measuring the organizational development of the associative organizations in the south of Colombia through members' and associates' perception regarding the intellectual capital developed in the components of human, structural and relational capital. The study was of a quantitative and descriptive type, in which the survey technique was used through a Likert-scale applied to members and associates of 27 associative organizations. Faced with the results, organizations were obtained with an organizational advance that exceeds 60% in the components of human and structural capital, which implies that the organizations developed aspects of human capital such as the knowledge of its members, the professional relevance, the processes of improvement and the antiquity of the association, while in the structural capital aspects such as standards and values, certifications and brands stand out and the revolving fund among others. Nevertheless, relational capital has not yet reached its development, especially in its marketing and business relations components. [ABSTRACT FROM AUTHOR]

Highlights • Identification of relevant consequences in Aviation Safety at state level. • Multiattribute utility models to forecast and assess consequences of occurrences. • Models to facilitate the definition of national Safety Management Systems. Abstract Aviation safety is essential for the healthy growth and sustainability of the global economy. The implementation of Safety Management Systems to support safe service delivery has become one of the most important goals within the airline industry over the last years. However, in most cases the involved organisations use unsophisticated methods based on risk matrices for the development of such systems. In this paper, we present models to forecast and assess the consequences of aviation safety occurrences as part of a framework for aviation safety risk management at state level. [ABSTRACT FROM AUTHOR]

Considering the need to develop strategies for dirty eggs incubation and the demand to use renewable methods of sanitation, the use of ultraviolet light for disinfecting hatching dirty eggs was the objective of this research. Eggs not disinfected (C-), disinfected with paraformaldehyde (C+) and exposed to different times of UV radiation (UV 3'30", UV 4'30" and UV 5'30") were tested. The eggs C(+) and those exposed to UV for 3'30" and 5'30" presented a significant reduction on the number of colonies of eggshells comparing to C(-), with a 0.64 to 1 logUFC/g variation. The treatments C(+), UV 3'30" and UV 5'30" were applied in an incubation phase. The hatchability of treatment UV 3'30" (70,51%) was superior to UV 5'30" (51,16%) and alike C(+) (55,81%). In conclusion, the treatment UV 3'30" is effective in reducing microbiologic contamination of dirty eggs and do not affect negatively hatchability and quality of chicks. [ABSTRACT FROM AUTHOR]

Background: CIGB-247, a VSSP-adjuvanted VEGF-based vaccine, was evaluated in a phase I clinical trial in patients with advanced solid tumors (CENTAURO). Vaccination with the maximum dose of antigen showed an excellent safety profile, exhibited the highest immunogenicity and was the only one showing a reduction on platelet VEGF bioavailability. However, this antigen dose level did not achieve a complete seroconversion rate in vaccinated patients. These clinical results led us to the question whether a "reserve" of untapped immune response potential against VEGF could exist in cancer patients. To address this matter, CENTAURO-2 clinical trial was conducted where antigen and VSSP dose scale up were studied, and also incorporated the exploration of aluminum phosphate as adjuvant. These changes were made with the aim to increase immune response against VEGF. Results: The present study reports the characterization of the humoral response elicited by CIGB-247 from the combining of different antigen doses and adjuvants. Cancer patients were immunologically monitored for approximately 1 year. Vaccination with different CIGB-247 formulations exhibited a very positive safety profile. Cancer patients developed IgM, IgG or IgA antibodies specific to VEGF. Elicited polyclonal antibodies had the ability to block the interaction between VEGF and its receptors, VEGFR1 and VEGFR2. The highest humoral response was detected in patients immunized with 800 μg of antigen + 200 µg of VSSP. Off-protocol long-term vaccination did not produce negative changes in humoral response. Conclusions: Vaccination with a human VEGF variant molecule as antigen in combination with VSSP or aluminum phosphate is immunogenic. The results of this study could contribute to the investigation of this vaccine therapy in an adequately powered efficacy trial. [ABSTRACT FROM AUTHOR]

CIGB-247 is a cancer therapeutic vaccine, based on recombinant modified human vascular endothelial growth factor (VEGF) as antigen, in combination with the adjuvant VSSP, a bacterially-derived adjuvant. The vaccine have demonstrated efficacy in several murine malignancy models. These studies supported the rationale for a phase I clinical trial where safety, tolerance, and immunogenicity of CIGB-247 was studied in patients with advanced solid tumors at three antigen dose level. Surviving individuals of this clinical trial were eligible to receive off-trial voluntary re-immunizations. The present work is focus in the immunological follow up of these patients after approximately three years of immunizations, without additional oncological treatments. Long term vaccination was feasible and safe. Our results indicated that after sustained vaccination most of the patients conserved their seroconversion status. The specific anti-VEGF IgG titer diminished, but in all the cases keeps values up from the pre-vaccination levels. Continued vaccination was also important to produce a gradual shift in the anti-VEGF IgG response from IgG1 to Ig4. Outstanding, our results indicated that long-term off-trial vaccination could be associated with the maintaining of one reserve of antibodies able to interfere with the VEGF/Receptor interaction and the production of IFNγ secretion in CD8 + cells. The results derived from the study of this series of patients suggest that long term therapeutic vaccination is a feasible strategy, and highlight the importance of continuing the clinical development program of this novel cancer therapeutic vaccine candidate. We also highlight the future clinical applications of CIGB-247 in cancer and explain knowledge gaps that future studies may address. Registration number and name of trial registry: RPCEC00000102. Cuban Public Clinical Trial Registry (WHO accepted Primary Registry). Available from: http://registroclinic o.s l d.c u/ . [ABSTRACT FROM AUTHOR]

BACKGROUND: Growth hormone-releasing peptides (GHRPs) constitute a group of small synthetic peptides that stimulate the growth hormone secretion and the downstream axis activity. Mounting evidences since the early 1980s delineated unexpected pharmacological cardioprotective and cytoprotective properties for the GHRPs. However, despite intense basic pharmacological research, alternatives to prevent cell and tissue demise before lethal insults have remained as an empty niche in the clinical armamentarium. Here, we have rigorously reviewed the investigational development of GHRPs and their clinical niching perspectives. METHODOLOGY: PubMed/MEDLINE databases, including original research and review articles, were explored. The search design was date escalated from 1980 and included articles in English only. RESULTS AND CONCLUSIONS: GHRPs bind to two different receptors (GHS-R1a and CD36), which redundantly or independently exert relevant biological effects. GHRPs' binding to CD36 activates prosurvival pathways such as PI-3K/AKT1, thus reducing cellular death. Furthermore, GHRPs decrease reactive oxygen species (ROS) spillover, enhance the antioxidant defenses, and reduce inflammation. These cytoprotective abilities have been revealed in cardiac, neuronal, gastrointestinal, and hepatic cells, representing a comprehensive spectrum of protection of parenchymal organs. Antifibrotic effects have been attributed to some of the GHRPs by counteracting fibrogenic cytokines. In addition, GHRP family members have shown a potent myotropic effect by promoting anabolia and inhibiting catabolia. Finally, GHRPs exhibit a broad safety profile in preclinical and clinical settings. Despite these fragmented lines incite to envision multiple pharmacological uses for GHRPs, especially as a myocardial reperfusion damage-attenuating candidate, this family of "drugable" peptides awaits for a definitive clinical niche. [ABSTRACT FROM AUTHOR]

CIGB-247, a VEGF-based vaccine, was studied in a clinical trial. This advance demands the refinement of the methodologies for assessment of vaccine immune responses. This study aimed to improve the performance of ELISAs for detecting IgG antibodies against human VEGF and the blocking activity of the serum to inhibit the VEGF/VEGFR2 interaction. The best experimental conditions were established through the evaluation of several blocking buffers, immobilization surfaces, and plate suppliers using human sera as test samples. As a result, two controlled ELISAs were used in testing of elicited immune response against VEGF in patients immunized with CIGB-247. [ABSTRACT FROM AUTHOR]

• Abscisic Acid (ABA) treatment can effectively prevent memory impairment in a murine model of Alzheimer disease (AD). • ABA treatment can prevent microglia transition to inflammatory state in transgenic model of AD. • The beneficial effects of ABA, PPARᵧ agonist and an insulin sensitizer in the central nervous system are independent of peripheral insulin resistance. • Further studies will establish whether later intervention (when the disease may be in initial stages), but longer treatments can guarantee better rescue of memory impairment. Neuroinflammation and insulin resistance in the brain are intimately linked to neurodegenerative disorders, including Alzheimer's disease. Even though traditionally Alzheimer´s disease has been associated to Aβ deposits and hyperphosphorylated Tau intracellular tangles, several studies show that neuroinflammation may be the initial cause that triggers degeneration. Accordingly, a number of natural supplements that improves brain insulin sensitivity and reduce neuroinflammation have been proposed as good choices in the therapeutic prevention of cognitive decline. Further supporting this evidence, we show that phytohormone Abscisic Acid, can prevent memory impairment and neuroinflammation markers in a triple transgenic mouse model, where no peripheral inflammatory changes have occurred. Moreover, our data strongly suggests that early intervention is critical for good prognosis, and that cognitive improvement requires longer treatment than recovering neuroinflammation markers. [ABSTRACT FROM AUTHOR]

Objectives: Vascular endothelial growth factor (VEGF) is involved in physiological angiogenesis, but also is considered one of the key factors that promotes tumor angiogenesis. CIGB-247 is a VEGF-based vaccine that has been evaluated in phase I clinical trial patients with advanced solid tumors. This specific active immunotherapy is able to reduce platelet VEGF levels; however it is unknown whether this effect leads to a decrease in VEGF below the levels that can be observed in healthy individuals. The objective of the present study is to investigate platelet VEGF levels in cancer patients vaccinated with CIGB-247, and then compare these values with those obtained in healthy individuals. To achieve this, platelet VEGF levels of 62 cancer patients and 93 healthy individuals were compared. Cancer patients were those individuals recruited in CENTAURO and CENTAURO-2 clinical trials. Results: Before vaccination, platelets of cancer patients carried more VEGF than the levels seen in platelet of healthy individuals. However, after vaccination, cancer patients had platelet VEGF values within the range established by healthy individuals, indicating that the antibody response elicited by CIGB-247 is not able to induce a complete suppression of VEGF. Vaccination with CIGB-247 helps to normalize VEGF levels within platelets. [ABSTRACT FROM AUTHOR]

A cooling system design for the processing of radioactive waste drums is investigated in this work, with the objective of providing insights for the determination of the air flow rate required to ensure an acceptable slag temperature (323 K or below) after 5 days. A methodology based on both 3D and 2D axisymmetric Computational Fluid Dynamics (CFD) modelling is developed. Transient temperature distributions within the drums in time and space determined by the heat transfer characteristics are studied in detail. A sensitivity analysis is also carried out assuming different physical properties of the radioactive slag. It was found out that for all variations analyzed, the maximum temperature of slag at the end of five days cooling is below 323 K, where the maximum outlet air temperature for a minimum air inlet velocity of 1 m/s is between 320 K and 323 K depending on the radioactive slag properties. When glass-like radioactive slag properties are assumed, the internal heat conduction within the slag is limiting the overall heat transfer, therefore requiring significantly longer cooling times. [ABSTRACT FROM AUTHOR]