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BACKGROUND: Vasculogenic mimicry (VM) is characterized by formation of three-dimensional (3D) channels-like structures by tumor cells, supplying the nutrients needed for tumor growth. VM is stimulated by hypoxic tumor microenvironment, and it has been associated with increased metastasis and clinical poor outcome in cancer patients. cAMP responsive element (CRE)-binding protein 5 (CREB5) is a hypoxia-activated transcription factor involved in tumorigenesis. However, CREB5 functions in VM and if its regulated by microRNAs remains unknown in breast cancer. OBJECTIVE: We aim to study the functional relationships between VM, CREB5 and microRNA-204-5p (miR-204) in breast cancer cells. METHODS: CREB5 expression was evaluated by mining the public databases, and using RT-qPCR and Western blot assays. CREB5 expression was silenced using short-hairpin RNAs in MDA-MB-231 and MCF-7 breast cancer cells. VM formation was analyzed using matrigel-based cultures in hypoxic conditions. MiR-204 expression was restored in cancer cells by transfection of RNA mimics. Luciferase reporter assays were performed to evaluate the binding of miR-204 to 3′UTR of CREB5. RESULTS: Our data showed that CREB5 mRNA expression was upregulated in a set of breast cancer cell lines and clinical tumors, and it was positively associated with poor prognosis in lymph nodes positive and grade 3 basal breast cancer patients. Silencing of CREB5 impaired the hypoxia-induced formation of 3D channels-like structures representative of the early stages of VM in MDA-MB-231 cells. In contrast, VM formation was not observed in MCF-7 cells. Interestingly, we found that CREB5 expression was negatively regulated by miR-204 mimics in breast cancer cells. Functional analysis confirmed that miR-204 binds to CREB5 3′-UTR indicating that it’s an ulterior effector. CONCLUSIONS: Our findings suggested that CREB5 could be a potential biomarker of disease progression in basal subtype of breast cancer, and that perturbations of the miR-204/CREB5 axis plays an important role in VM development in breast cancer cells.

Objetivo. Describir las barreras de acceso y disponibilidad en laboratorios clínicos de emergencia en dos hospitales tipo IV con diferente localización geográfica en la Región Zuliana. Método. Estudio descriptivo y comparativo, con diseño no experimental transversal. Muestreo no probabilístico con tamaño muestral de 290 usuarios del servicio, 80 del Hospital 1 (H1) y 210 del Hospital 2 (H2). Los datos fueron obtenidos a través de encuesta mixta de elaboración propia, validada mediante concordancia entre expertos. Se utilizaron estadísticos descriptivos y comparación de medias, mediante la técnica T Student al 95% de confianza. Resultados. La principal barrera de acceso encontrada fue la geográfica, en el H1 (97,5 %) y el H2 (71,9 %). Se hallaron diferencias en la forma de traslado y tiempo requerido para llegar al centro de salud; en el H1 los pacientes utilizan sus vehículos (48,8 %) con tiempo de traslado 13,25±4,71 minutos; y en el H2 se utiliza principalmente transporte público (74,3 %) con tiempo de traslado mayor (50,09±34,4 min). La principal barrera administrativa fue la falta de insumos básicos (97,5% H1 vs 98,1% H2). Existen barreras económicas en ambos centros de salud: 53,8% en el H1 y 56,7% para el H2. Se evidenció mayor disponibilidad de pruebas en el laboratorio de emergencias del H1 (85,6 %) que en el H2 (31,72%). Conclusión. Existen barreras de acceso de tipo geográficas, administrativas, económicas y diferencias en la disponibilidad de insumos entre los laboratorios de los dos hospitales.

Table S1: All somatic mutations and short insertion/deletions. This table provides information on all somatic point mutations and short insertion/deletions observed in the tumor sample from this patient. Additional annotations about protein change, allelic fraction, copy ratio (as segment mean), and other information are provided.

PD-1 immune checkpoint blockade occasionally results in durable clinical responses in advanced metastatic cancers. However, mechanism-based predictors of response to this immunotherapy remain incompletely characterized. We performed comprehensive genomic profiling on a tumor and germline sample from a patient with refractory lung adenocarcinoma who achieved marked long-term clinical benefit from anti–PD-L1 therapy. We discovered activating somatic and germline amino acid variants in JAK3 that promoted PD-L1 induction in lung cancer cells and in the tumor immune microenvironment. These findings suggest that genomic alterations that deregulate cytokine receptor signal transduction could contribute to PD-L1 activation and engagement of the PD-1 immune checkpoint in lung cancer. Cancer Immunol Res; 3(8); 855–63. ©2015 AACR.

Figure S1: Orthogonal sequencing of JAK3 mutations. Figure S2: Copy number profile of tumor. Figure S3: Absolute copy number. Figure S4: PHIAL gel of patient's somatic exome results. Figure S5. Modified H-scores for tumor and immune cells. Figure S6. T cell re-activation following co-culture with JAK3-V722I expressing monocytes in the presence of MPDL3280A.

Viviparity evolved independently about 150 times in vertebrates and more than 20 times in fish. Several lineages added to the protection of the embryo inside the body of the mother, the provisioning of nutrients, and physiological exchange. This often led to the evolution of a placenta. Among fish, one of the most complex systems serving the function of the placenta is the embryonal trophotaenia/ovarian luminal epithelium of the goodeid fishes. For a better understanding of this feature and others of this group of fishes, high-quality genomic resources are essential. We have sequenced the genome of the darkedged splitfin, Girardinichthys multiradiatus. The assembly is chromosome level and includes the X and Y Chromosomes. A large male-specific region on the Y was identified covering 80% of Chromosome 20, allowing some first inferences on the recent origin and a candidate male sex determining gene. Genome-wide transcriptomics uncovered sex-specific differences in brain gene expression with an enrichment for neurosteroidogenesis and testis genes in males. The expression signatures of the splitfin embryonal and maternal placenta showed overlap with homologous tissues including human placenta, the ovarian follicle epithelium of matrotrophic poeciliid fish species and the brood pouch epithelium of the seahorse. Our comparative analyses on the evolution of embryonal and maternal placenta indicate that the evolutionary novelty of maternal provisioning development repeatedly made use of genes that already had the same function in other tissues. In this way, preexisting modules are assembled and repurposed to provide the molecular changes for this novel trait.

The California-Mexico border region is a high-volume trauma area with populations of widely disparate socioeconomic status. This work analyzed differences in demographics and mechanism of injury in children using the Area Deprivation Index (ADI), a composite measure of 17 markers of neighborhood socioeconomic disadvantage.A retrospective review was performed of pediatric patients evaluated at the regional Level I Pediatric Trauma Center between 2008 and 2018. Collected data included patient demographics and injury characteristics. Patient addresses were correlated to neighborhood disadvantage level using ADI quintiles, with a higher quintile representing greater socioeconomic disadvantage.A total of 9,715 children were identified, of which 4,307 (44%) were Hispanic. Hispanic children were more likely to live in more disadvantaged neighborhoods than non-Hispanic children (p0.001). There were markedly different injury mechanisms in neighborhoods with greater socioeconomic disadvantage (higher ADI) compared with those with less socioeconomic disadvantage. Sports-related and nonmotorized vehicular trauma predominated in less disadvantaged neighborhoods, while higher ADI quintiles were strongly associated with pedestrian versus automobile, motorized vehicle accidents/collisions, and nonaccidental injuries (p0.001).This analysis represents the first study to characterize pediatric traumatic injury patterns based upon the neighborhood ADI metric. Area Deprivation Index can be a useful resource in identifying disparities in pediatric trauma and children at increased risk for vehicular and abusive injury who may benefit from increased resource allocation, social support, and prevention programs.Prognostic and epidemiological, Level III.

Differential atmospheric dispersion is a wavelength-dependent effect introduced by the atmosphere. It is one of the instrumental errors that can affect the position of the target as perceived on the sky and its flux distribution. This effect will affect the results of astronomical observations if not corrected by an atmospheric dispersion corrector (ADC). In high-resolution spectrographs, in order to reach a radial velocity (RV) precision of 10 cm/s, an ADC is expected to return residuals at only a few tens of milli-arcseconds (mas). In fact, current state-of-the-art spectrographs conservatively require this level of residuals, although no work has been done to quantify the impact of atmospheric dispersion. In this work we test the effect of atmospheric dispersion on astronomical observations in general, and in particular on RV precision degradation and flux losses. Our scientific objective was to quantify the amount of residuals needed to fulfill the requirements set on an ADC during the design phase. We found that up to a dispersion of 100 mas, the effect on the RV is negligible. However, on the flux losses, such a dispersion can create a loss of ~2% at 380 nm, a significant value when efficiency is critical. The requirements set on ADC residuals should take into consideration the atmospheric conditions where the ADC will function, and also all the aspects related with not only the RV precision requirements but also the guiding camera used, the tolerances on the flux loss, and the different melt data of the chosen glasses., Comment: accepted for publications in MNRAS

Biologics have improved the treatment of rheumatic diseases, resulting in better outcomes. However, their high cost limits access for many patients in both North America and Latin America. Following patent expiration for biologicals, the availability of biosimilars, which typically are less expensive due to lower development costs, provides additional treatment options for patients with rheumatic diseases. The availability of biosimilars in North American and Latin American countries is evolving, with differing regulations and clinical indications. The objective of the study was to present the consensus statement on biosimilars in rheumatology developed by Pan American League of Associations for Rheumatology (PANLAR). Using a modified Delphi process approach, the following topics were addressed: regulation, efficacy and safety, extrapolation of indications, interchangeability, automatic substitution, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. Consensus was achieved when there was agreement among 80% or more of the panel members. Three Delphi rounds were conducted to reach consensus. Questionnaires were sent electronically to panel members and comments about each question were solicited. Eight recommendations were formulated regarding regulation, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. The recommendations highlighted that, after receiving regulatory approval, pharmacovigilance is a fundamental strategy to ensure safety of all medications. Registries should be employed to monitor use of biosimilars and to identify potential adverse effects. The price of biosimilars should be significantly lower than that of reference products to enhance patient access. Biomimics are not biosimilars and, if they are to be marketed, they must first be evaluated and approved according to established regulatory pathways for novel biopharmaceuticals. • Biologics have improved the treatment of rheumatic diseases. • Their high cost limits access for many patients in both North America and Latin America. • Biosimilars typically are less expensive, providing additional treatment options for patients with rheumatic diseases. • PANLAR presents its consensus on biosimilars in rheumatology

Viviparity evolved independently about 150 times in vertebrates and more than 20 times in fish. Several lineages added to the protection of the embryo inside the body of the mother, the provisioning of nutrients, and physiological exchange. This often led to the evolution of a placenta. Among fish, one of the most complex systems serving the function of the placenta is the embryonal trophotaenia/ovarian luminal epithelium of the goodeid fishes. For a better understanding of this feature and others of this group of fishes, high-quality genomic resources are essential. We have sequenced the genome of the darkedged splitfin

Aims. We report on ESPRESSO high-resolution transmission spectroscopic observations of two primary transits of the highly-irradiated, ultra-hot Jupiter-size planet WASP-76b. We investigate the presence of several key atomic and molecular features of interest that may reveal the atmospheric properties of the planet. Methods. We extracted two transmission spectra of WASP-76b with R approx 140,000 using a procedure that allowed us to process the full ESPRESSO wavelength range (3800-7880 A) simultaneously. We observed that at a high signal-to-noise ratio, the continuum of ESPRESSO spectra shows wiggles that are likely caused by an interference pattern outside the spectrograph. To search for the planetary features, we visually analysed the extracted transmission spectra and cross-correlated the observations against theoretical spectra of different atomic and molecular species. Results. The following atomic features are detected: Li I, Na I, Mg I, Ca II, Mn I, K I, and Fe I. All are detected with a confidence level between 9.2 sigma (Na I) and 2.8 sigma (Mg I). We did not detect the following species: Ti I, Cr I, Ni I, TiO, VO, and ZrO. We impose the following 1 sigma upper limits on their detectability: 60, 77, 122, 6, 8, and 8 ppm, respectively. Conclusions. We report the detection of Li I on WASP-76b for the first time. In addition, we found the presence of Na I and Fe I as previously reported in the literature. We show that the procedure employed in this work can detect features down to the level of ~ 0.1 % in the transmission spectrum and ~ 10 ppm by means of a cross-correlation method. We discuss the presence of neutral and singly ionised features in the atmosphere of WASP-76b., 20 pages, 19 figures, accepted for publication in Astronomy and Astrophysics

Differential atmospheric dispersion is a wavelength-dependent effect introduced by Earth's atmosphere that affects astronomical observations performed using ground-based telescopes. It is important, when observing at a zenithal angle different from zero, to use an Atmospheric Dispersion Corrector (ADC) to compensate this atmospheric dispersion. The design of an ADC is based on atmospheric models that, to the best of our knowledge, were never tested against on-sky measurements. We present an extensive models analysis in the wavelength range of 315-665 nm. The method we used was previously described in the paper I of this series. It is based on the use of cross-dispersion spectrographs to determine the position of the centroid of the spatial profile at each wavelength of each spectral order. The accuracy of the method is 18 mas. At this level, we are able to compare and characterize the different atmospheric dispersion models of interest. For better future ADC designs, we recommend to avoid the Zemax model, and in particular in the blue range of the spectra, when expecting residuals at the level of few tens of milli-arcseconds., Comment: Accepted for publications in MNRAS

ESPRESSO is a high resolution, super stable fiber-fed echelle spectrograph, installed at the ESO-VLT Combined Coude Laboratory of the Paranal Observatory. The main instrument subsystems are: Coude Path, Fiber Link (FL) and Spectrograph. After installation and verification, the FL subsystem flux efficiency did not fully meet the requirements. We describe the FL subsystem upgrade, required in order to improve the optical efficiency and to meet the throughput specifications. We present the opto-mechanical design improvements, aimed to ensure proper reliability and stability of the FL subsystem both in the alignment phase and in the integration on the spectrograph. Moreover, we summarize the activities done for the different units along the upgrade phases: AIT in laboratory, FL subsystem integration on the spectrograph at VLT and on-site efficiency verifications. Measurements done before and during instrument re- commissioning show a throughput improvement of more than 30%.

Since the first discovery of a planet outside of our Solar System in 1995, exoplanet research has shifted from detecting to characterizing worlds around other stars. The TESS (NASA, launched 2019) and PLATO mission (ESA, planned launch 2026) will find and constrain the size of thousands of exoplanets around bright stars all over the sky. Radial velocity measurements are needed to characterize the orbit and mass, and complete the picture of densities and composition of the exoplanet systems found. The Ariel mission (ESA, planned launch 2028) will characterize exoplanet atmospheres with infrared spectroscopy. Characterization of stellar activity using optical spectroscopy from the ground is key to retrieve the spectral footprint of the planetary atmosphere in Ariel's spectra. To enable the scientific harvest of the TESS, PLATO and Ariel space missions, we plan to install MARVEL as an extension of the existing Mercator Telescope at the Roque De Los Muchachos Observatory on La Palma (SPAIN). MARVEL consists of an array of four 80 cm telescopes linked through optical fibers to a single high-resolution echelle spectrograph, optimized for extreme-precision radial velocity measurements. It can observe the radial velocities of four different stars simultaneously or, alternatively, combine the flux from four telescopes pointing to a single faint target in one spectrum. MARVEL is constructed by a KU Leuven (Belgium) led collaboration, with contributions from the UK, Austria, Australia, Sweden, Denmark and Spain. In this paper, we present the MARVEL instrument with special focus on the optical design and expected performance of the spectrograph, and report on the status of the project., SPIE Astronomical Telescopes + Instrumentation 2020, Ground-based and Airborne Instrumentation for Astronomy VIII

Modern pediatric neurosurgery succeeded in reducing ventricle-peritoneal shunt malfunctions and shunt revisions. However, some children may be submitted to many surgeries, posing burden to their caregivers. And most of caregiver assume responsibility for care without emotional preparation. It is up to health professionals to carry out the educational process. The aim of this study was to evaluate the knowledge, attitude, and practice of informal caregivers of children with hydrocephalus before and after intervention with previously developed educational material.This is a quasi-experimental, before-and-after study conducted with 32 informal caregivers of children with hydrocephalus. Data collection occurred in three stages: pre-test, educational intervention through educational material, and post-test. The knowledge, attitude, and practice survey was used as a pre-test and post-test assessment tool.The mean score in the three domains (knowledge, attitude, and practice) was lower in the pre-test compared to the post-test. After caregivers read the educational material, the correct answer rate increased by 17% in the knowledge domain and 21.4% in the practice domain, with p values of0.01. In the attitude domain, there was a non-significant increase of 0.06 (2.0%, p = 0.161) points in the mean score between the pre-test and the post-test.The educational material enables the acquisition of knowledge of informal caregivers of children with hydrocephalus. This can be used by health professionals to strengthen the bond between professional care staff and family, and to facilitate the educational process.

Contains fulltext : 229416.pdf (Publisher’s version ) (Open Access) This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The first part of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline. Suggestions for disease severity grading and treatment goals are provided. It presents the general treatment recommendations as well as detailed management and monitoring recommendations for the individual drugs. The treatment options discussed in this guideline are as follows: acitretin, ciclosporin, fumarates, methotrexate, adalimumab, apremilast, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab.

Supplemental material, DS_10.1177_0022034520905660 for Efficacy of Alveolar Ridge Preservation: A Randomized Controlled Trial by G. Avila-Ortiz, M. Gubler, M. Romero-Bustillos, C.L. Nicholas, M.B. Zimmerman and C.A. Barwacz in Journal of Dental Research

The very short burn time and small size of burning plasmas created at advanced laser-fusion facilities will require high-spatial-resolution imaging diagnostics with fast time resolution. These instruments will need to function in an environment of extremely large neutron fluxes that will cause conventional diagnostics to fail because of radiation damage and induced background levels. One solution to this challenge is to perform an ultrafast conversion of the x-ray signals into the optical regime before the neutrons are able to reach the detector and then to relay image the signal out of the chamber and into a shielded bunker, protected from the effects of these neutrons. With this goal in mind, the OMEGA laser was used to demonstrate high-temporal-resolution x-ray imaging by using an x-ray snout to image an imploding backlighter capsule onto a semiconductor. The semiconductor was simultaneously probed with the existing velocity interferometry system for any surface reflector (VISAR) diagnostic, which uses an optical streak camera and provided a one-dimensional image of the phase in the semiconductor as a function of time. The phase induced in the semiconductor was linearly proportional to the x-ray emission from the backlighter capsule. This approach would then allow a sacrificial semiconductor to be attached at the end of an optical train with the VISAR and optical streak camera placed in a shielded bunker to operate in a high neutron environment and obtain time-dependent one-dimensional x-ray images or time-dependent x-ray spectra from a burning plasma.

It is reported in this study the effect of isolates from leaves of Aristotelia chilensis as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase enzymes. The aim of the paper was to evaluate the activity of A. chilensis towards different enzymes. In addition to pure compounds, extracts rich in alkaloids and phenolics were tested. The most active F5 inhibited AChE (79.5% and 89.8% at 10.0 and 20.0 μg/mL) and against BChE (89.5% and 97.8% at 10.0 and 20.0 μg/mL), showing a strong mixed-type inhibition against AChE and BChE. F3 (a mixture of flavonoids and phenolics acids), showed IC50 of 90.7 and 59.6 μg/mL of inhibitory activity against AChE and BChE, inhibiting the acetylcholinesterase competitively. Additionally, F3 showed and high potency as tyrosinase inhibitor with IC50 at 8.4 μg/mL. Sample F4 (anthocyanidins and phenolic composition) presented a complex, mixed-type inhibition of tyrosinase with a IC50 of 39.8 μg/mL. The findings in this investigation show that this natural resource has a strong potential for future research in the search of new phytotherapeutic treatments for cholinergic deterioration ailments avoiding the side effects of synthetic drugs. This is the first report as cholinesterases and tyrosinase inhibitors of alkaloids and phenolics from A. chilensis leaves.

This work considers an extension of the fractional-order Maxwell arrangement to incorporate a relaxation process with non-Newtonian viscosity behavior. The resulting model becomes a fractional-order nonlinear differential equation with stable solution converging asymptotically to a unique equilibrium point. Expressions for the corresponding storage and loss moduli as function of strain frequency and amplitude are computed via a first-harmonic analysis of the differential equation. Some distinctive features and their relationship to the classical and fractional-order linear Maxwell models are discussed. Three examples are used to illustrate the ability of the fractional-order Maxwell model to describe experimental data.

Summary This study was performed in Ross 308 chickens aged 1–21 days and aimed to evaluate whether the addition of 25-hydroxycholecalciferol (25(OH)D3) to broiler chicken diets affects their growth performance and immunity. A completely random 2 × 2 factorial arrangement was used with two levels of vitamin D3 and the absence or presence of 25(OH)D3, corresponding to four treatments based on sorghum + soya bean diets: (i) 200 IU of vitamin D3/kg of feed (Diet 1) (NRC, 1994), (ii) Diet 1 + 69 μg of 25(OH)D3/kg of feed (Diet 2), (iii) 5,000 IU of vitamin D3/kg of feed (Diet 3) and (iv) Diet 3 + 69 μg of 25(OH)D3/kg of feed (Diet 4). Each treatment was conducted with six replicates of 10 chickens each. Water and feed was supplied ad libitum. The results showed significantly increased growth and tibia ash (p

We present the design, manufacturing, test and performance of two image slicers for high resolution spectroscopy. Based on the classical Bowen-Walraven concept, our slicers allow to make two slices of the image of the input fibre. We introduce the idea of a second fibre that can be cropped in half to reach the same width of the science target fibre and that can be used for simultaneous wavelength reference. The slicers presented are mirror and prism based, respectively. Both devices work within expectation, showing differences mainly in their efficiency. The prism based slicer is the solution that was adopted for the FIDEOS spectrograph, an instrument built by the AIUC for the ESO 1m telescope of La Silla. Test spectra obtained with this instrument are included as examples of a real application of the device.

The objective of the study was to compare the effects of caudal epidural bupivacaine and dexmedetomidine (DEX) combination, with bupivacaine or DEX plain for perineal analgesia in mares. Six healthy saddle mares weighing 330–370 kg and aged 10–15 years were used in this study. Each mare was assigned to receive three treatments: 0.04 mg/kg 0.25% bupivacaine (BP), 2 μg/kg DEX (DX), or 0.02 mg/kg bupivacaine and 1 μg/kg DEX (BPDX). The order of treatments was randomized. All drugs were injected into the caudal epidural space (Co1-Co2) through a 16-G Tuohy epidural needle. After the epidural injections, heart rate, respiratory rate, arterial blood pressures (systolic, diastolic, and mean), and rectal temperature were measured at 5, 10, 15, 30, 60, 90, and 120 minutes, and after this time, every 60 minutes until the end of the experiments. A subjective score system was used to assess analgesia, behavioral and motor blockade at the same time points. The BPDX treatment produced analgesic action with twice the duration (200 minutes) of the BP treatment (97 minutes), but with an analgesic duration shorter than the DX treatment (240 minutes) in the regions of the tail, perineum, and upper hind limbs in mares. All treatments showed mild motor blockade. No behavioral changes were observed in any of the animals. There was hemodynamic stability without significant changes in respiratory rate for all treatments. Epidural analgesia using DEX alone or the combination of DEX and bupivacaine may be an option for painful obstetric and gynecological procedures in mares.

This protocol presents the usage and methodology for a PTNG test bench version 1, the device is presented in following image: The electrical components part of the test bench and its technical specifications are listed in table 1.

Molecular-assisted alpha taxonomy has provided novel ways of exploring biodiversity, and is of great help in taxa where morphology alone is not sufficient to ensure accurate species recognition or delimit species boundaries. Here, we use this approach to assess the taxonomy of Padina Adanson (Dictyotales, Phaeophyceae), a common brown algal genus in Mexican waters. Numerous individuals of Padina from Pacific and Atlantic tropical coasts were analysed using sequences of psbA, cytochrome c oxidase subunit I, and cox3 to determine evolutionary significant units or putative species. Then, cox3 sequences of some individuals of each group were analysed with a large number of sequences available in Genbank using the generalized mixed Yule coalescent and Poisson tree processes models for species delimitation. Each sample was identified using the original and the most common descriptions in the region. Last, the results were evaluated looking for correlations between the molecular and morphological data. ...

We explain in some detail the geometric structure of spheres in any dimension. Our approach may be helpful for other homogeneous spaces (with other signatures) such as the de Sitter and anti-de Sitter spaces. We apply the procedure to the recently proposed division-algebras/Poincar\'e-conjecture correspondence. Moreover, we explore the possibility of a connection between N-qubit system and the Hopf maps. We also discuss the possible links of our work with squashed-spheres in supergravity and pseudo-spheres in oriented matroid theory., Comment: 20 pages, Latex. arXiv admin note: substantial text overlap with arXiv:1303.2673

Single droplet drying experiments were conducted with solutions of dairy materials in water (skim milk and its constituents, namely lactose, whey protein and a lactose-whey mixture) at both moderate and elevated temperatures, at which inflation/deflation phenomena are observed. The experimental data were used to obtain parameters of a spatially resolving single droplet drying model, which was extended to empirically account for inflation/deflation. Inflation/deflation parameters and conditions for crust formation at the transition from the first to the second drying stage were clearly solute-dependent, and respective correlations with drying conditions were developed for the investigated dairy materials. The parametrized model was shown to satisfactorily describe measured data in respect to drying curve, drying time and the diameter of product particles.

In this work, a suspension device is presented that can be used for the investigation of single droplet drying kinetics at temperatures from ambient to 200°C. Evaluation is hybrid, using both camer...

The Cox–Merz rule (CMR) is commonly used for identifying similarities between the rheological results obtained from incremental and oscillatory fluid deformation tests. The CMR states that the steady state viscosity ηss(γ˙) and the complex viscosity η∗(ω) are similar when the equivalence ω↔γ˙ is considered. The empirical applicability of the CMR for diverse food material has been tested in recent decades, showing non-conclusive results for a diversity of foods. This work used the Kelvin–Voigt and Maxwell phenomenological models of power-law fluids to obtain equivalences between the steady state and the complex viscosities. Modified CMR rules (MCMR) were derived using first-harmonic balances for the underlying differential equations governing the strain dynamics. It is shown that the structure and applicability of the MCMR depended on the underlying model. Only the loss modulus was involved in the viscosity estimation for Kelvin–Voigt models while the traditional CMR was consistent with Maxwell model in the low-frequency regimen.

Background:Follow-up cohorts (observational studies) were initiated consecutively or simultaneously to the development of randomised controlled trials (RCTs) in JIA patients(1,2). They help to identify many complications observed only in clinical practice related to off label use, coadministration of treatments, drug misuse, and occurrence of rare or unexpected event. In addition, observational studies include a higher number of patients with a longer duration of follow-up compared to randomised trials. Hence, they have a higher power to capture the occurrence of serious adverse events (SAE) in daily clinical practice3.Objectives:To estimate the incidence of serious adverse events (SAEs) including serious infections, malignancies, and death in patients with juvenile idiopathic arthritis (JIA) treated with biological agents (BAs) in daily clinical practice, using meta-analysis techniques.Methods:We systematically searched, up to May 2019, Medline and Embase databases for observational studies performed in JIA disease under BAs treatment. Outcomes were SAEs, serious infections, malignancies and all-cause mortality. Complementary, the incidence of SAEs in randomised controlled trials (RCTs) with withdrawal and parallel designs was performed by meta-analysis.Results:A total of 31 observational studies were included (6811 patients totalizing 17530 patients-years [PY] of follow-up). The incidence rate of SAEs was similar in observational cohorts and withdrawal RCTs (4.46 events per 100 PY, 95% CI 2.85- 6.38, I2= 95%) and 3.71 events per 100 PY (95%CI 0.0-13.34), I2= 56%, respectively). The incidence of SAE was lower in parallel RCT. The incidence rate of serious infections, malignancies and death in observational cohorts was estimated at 0.74 events per 100 PY (95%CI 0.32-1.30, I2=83%), 0.10 events per 100 PY (95% CI 0.06-0.16, I2=0%) and 0.09 events per 100 PY (95% CI 0.05-0.14, I2=0%), respectively. Infections were the known cause of death in 8 of the 14 deaths. In meta-regression and subgroup analysis, variation of serious infections rates were partially explained by follow-up time (R2= 30.3%, p= 0.0008), JIA categories (all JIA versus polyarticular versus systemic JIA categories, p= 0.001) and cohort quality (Newcastle-Ottawa score ≥ to 6 versus ≤ to 5 stars, p= 0.0025).Conclusion:Our results suggest that the incidence rate of SAEs related to BAs in JIA disease is similar to those observed in randomised withdrawal trials. The overall incidence remained low. However, unsatisfactory description of SAEs prevents analysis of hospitalisation causes. Infection and, to a lesser extent, cancer and death, explain only part of burden of BAs.References:[1]Berard RA, Laxer RM. Learning the hard way: clinical trials in juvenile idiopathic arthritis. Ann Rheum Dis. 2018;77(1):1–2.[2]Swart J, Giancane G, Horneff G, Magnusson B, Hofer M, Alexeeva Е, et al. Pharmacovigilance in juvenile idiopathic arthritis patients treated with biologic or synthetic drugs: combined data of more than 15,000 patients from Pharmachild and national registries. Arthritis Res Ther. 2018 27;20(1):285.[3]Monti S, Grosso V, Todoerti M, Caporali R. Randomized controlled trials and real-world data: differences and similarities to untangle literature data. Rheumatol Oxf Engl. 2018 01;57(57 Suppl 7):vii54–Disclosure of Interests:None declared

Background Rheumatoid Arthritis is a chronic rheumatic disease characterised by polyarticular inflammation. The rheumatoid factor is one of the most known prognostic markers, not only its presence, but also the levels. It also presents different isotypes (IgG, IgM, IgA), which can affect the course of the disease. Objectives To analyse the presence of different rheumatoid factor (RF) isotypes in Paraguayan patients with rheumatoid arthritis (RA) and to study their association with clinical and analytical characteristics. Methods Descriptive, cross-sectional study. A large number of clinical and serological variables were recorded. The anti-CCP 3.1 and Rheumatoid factor (RF) isotypes IgA, IgG, and IgM were measured in serum samples by ELISA (enzyme-linked immunosorbent assay) (NV Results 103 patients with RA were included, 86.4% were female, with a median age of onset of 44.7±13.6 years, and the mean disease duration was 7.13±7.03 years. The olygoarticular onset was the most frequent (46.6%). 13.7% were smokers. Extra-articular manifestations were present in 13.5%. The most frequent treatment was methotrexate (84.3%). Erosions were observed in 43.2% of patients. 28% were in remission of the disease measured by the DAS28 index. The average of HAQ was 0.47%±0.58. 91.3% had anti-CCP positive, the mean anti-CCP levels were 290.5±152.8 U/mL. RF isotypes was observed in 75.7%, 53.4% and 38.8% for IgM, IgA and IgG respectively. Mean levels were as follow, IgA 85.62±56.6 U/mL, IgM 96.7±30.9 U/mL, IgG 70.98±72.42 U/mL. 32% of the patients had 2 isotypes of RF, while 25.2% had the 3 isotypes. The 57.3% had ≥2 isotypes of RF. We did not find significant differences when comparing gender, age, disease duration, form of onset, extra-articular manifestations, smoking status, erosions, disease activity, HAQ, treatment, between the different RF isotypes, and levels, except in the presence of anti-CCP with the RF-IgM isotype (p Conclusions This is the first study of RF isotypes in Paraguayan patients with RA. The most frequent isotype of RF was IgM. More than 50% of patients had 2 or more RF isotypes. The majority of patients with positive RF had high levels of different isotypes, being the highest IgM. Disclosure of Interest None declared

Background The PANLAR-EOA (early-onset-arthritis) project includes panamericanrheumatologists to determine regional characteristics of patients with early onset arthritis. Objectives To describe the cohort of Paraguayan patients included in PANLAR-EOA project. Methods Longitudinal, prospective, multicentricstudy. Patients were included according to the PANLAR-EOA project and registered in REPANARC(www.panlareoa.org) database. At baseline and annual visits, a large number of demographic, clinical and analytical variables were recorded. Quantitative variables were characterised by their means and standard deviations, while the qualitative variables were characterised according to the percentage of patients. The comparison of epidemiological and clinical variables was performed using the chi-squared test and the Wilcoxon test respectively for qualitative and quantitative variables, respectively. Results 136 patients with early onset arthritis were included, out of which 88 completed the 12 months follow up and 58 the 24 months one. In these, 86%were female with a median age of 43.9±13.2 years. The most frequent race was mestiza in 80.1%. According to GRAFFAR index, middle class was the predominant social stratum (9.8±3.1). The average number of years of schooling was 12.8±3.8. Polyarticular onset was registeredin 61% patients. During follow-up, 43.1% had positive rheumatoid factor and 56.5% positive anti-CCP. The diagnostic delay was 3.9±3.0 months. Initially, 63.2% (86/136) were diagnosed with rheumatoid arthritis (RA) and 36.8% (50/136) with undifferentiated arthritis (UA). The most frequent treatment was methotrexate (85.3%, 90.9%, and 89.3% at baseline, 1 and 2 years of follow-up respectively). During follow-up, a significant diagnostic change was observed in patients with UA (p=0.004, OR=2.9 [95%CI, 1.4–6.5]). The variables associated with RA diagnosis werepresence of anti-CCP (p=0.000, OR=15.8 [95%CI,5.4–51.1]), rheumatoid factor (p=0.000, OR=9.2 [95%CI,3.4–27.0]), smoking (p=0.032, OR=8.8 [95%CI,1.1–404.7]), high body mass index (p=0.041, OR=1.94 [95%CI,−0.2–4.1]) and high activity measured by the DAS28 index (p=0.01). After one year of follow-up there was a significant decrease in disease activity according to DAS 28 (p=2.2e-09[95% CI, −1.5,–0.9]), SDAI(p=1.2e-11[95% CI, 18.2,–11.2]) and HAQ (p=7.2e-08[95% CI,−0.7,–0.4]). Similar results were found at the 2nd year of follow-up, DAS28 (p=8.8e-06[95% CI,−1.6,–0.7]), SDAI (p=2.1 e- 07 [95% CI,−20.0,−10.3]) and HAQ (p=3.4e-08[95% CI,−0.9,–0.5]). Conclusions In this cohort of early onset arthritis, diagnostic delay was lower than that observed in other series and the rate of change from diagnosis of UA to RA was statistically significant during the first year of follow-up. A good control of the inflammatory activity of the disease was observed, with a significant improvement of all the variables analysed during its evolution. Disclosure of Interest None declared

The two co-authors of the mentioned above article were incorrect. The correct are authors should have been "P. A. Beltrán" instead of "P. A. B. Roa" and "J. F. Diaz-Coto" instead of "L. Diaz Soto".

The aim of this work is to study the rheological response of gelatinized starch dispersions under constant shear stress. To this end, starch dispersions at four different starch concentrations, were prepared by stirring and heating at 90 °C by 20 min. The experiments showed that the mechanical (i.e., strain) response is composed by a long-term trend that can be described by a two-relaxation mode process, and a high-frequency unstable response. Optical images indicated that the compact packing of the insoluble amylose-rich material, known as ghosts, is responsible for the unstable flow response. In fact, after destroying the starch dispersion microstructure with severe shear conditions (sonication), it was observed that the unstable flow response was no longer present. Fourier and fractal (DFA) analyses showed that the scaling characteristics of the strain instabilities depend on the starch concentration and the applied shear stress value. Also, the characteristic flow curves suggested that yield stress and non-monotonous flow curves are at the center of the mechanisms triggering elastic turbulence in starch dispersions.

Mucilage from chia (Salvia hispanica L.) seed contains carbohydrate polymers with high solubility. It forms highly viscous solutions at low concentrations, and possesses the ability to adsorb at interfaces because of the small amount of protein it contains (∼4.0%). The aim of this work was to study the viscoelastic properties of chia seed mucilage to gain insights regarding the formation structures at the oil-water interface and in the vicinity of the aqueous bulk phase. The rationale was that emulsions with enhanced viscoelastic properties at the vicinity of the interface are more likely to resist instabilities in the face of shear stress disturbances and exhibit long-term viability and stability. A constant shear stress was applied at the oil-water interface and at different distances from it, leading to underdamped inertio-elastic oscillations. It was found that the viscous and elastic moduli decreased and the inertia increased as the oil-water interface was approached from the aqueous phase. The results are discussed in terms of the possible stratification of the mucilage material at the oil-water interface.

Evidences about the biosynthesis of secondary metabolites from plants point to constitutive or induce chemical defense generated for protection against to different phytopathogenic attack. Calceolaria spp. is regarded both as a notorious weed and as a popular ornamental garden plant and have medicinal application. Some taxa of the America distributed Calceolaria genus are toxic to insects, fungi and several bacteria strains, and its effect has been associated with the presence of phenolics. Calceolaria spp. produces a number of iridoids, flavonoids, naphthoquinones and phenylpropanoids that have been shown to possess interesting biological activities. All these aspects are considered in this review to allow an evaluation of the potential for utilization of the large biodiversity of Calceolaria available. An up-to-date of the phytochemistry and biological activities of several members of the Calceolariaceae family is show. New iridoids, flavonoids and phenylpropanoids for these Calceolaria species have been isolated, identified and tested for their antifeedant, igr, insecticidal, antimicrobial, anticancer, proteinase, tyrosinase, and acetylcholinesterase inhibitory activities. Until now mixtures of flavonoids have been found to be potent insecticides and fungicides, followed by phenylpropanoids mixtures and iridoids showed to be antifeedant and in some cases repellent and attractant. Dose-dependent experiments shows that flavonoids are insecticidal against S. frugiperda and D. melanogaster at early growth stages. Bactericidal and fungicidal activity showed that dunnione (a naphthoquinone) have potent activity as fungistatic and fungicidal. O-methylflavonols, and different mixtures of them were very effective fungistatic. However, fungistatic quercetin and dunnione both combined with sublethal amount of kaempferol and gallic acid showed a strong fungicidal activity against phytopathogenic strains. Additionally, naphthoquinones possess a promissory activity as anticancer.

Corn and wheat gelatinized starch dispersions (GSD, 5.0% w/w) were prepared (90 °C, 20 min). The apparent viscosity-shear rate (0.0001–1 s−1) profile of the both GSD showed a shear thickening behaviour region (∼0.0002–0.003 s−1) followed by a shear thinning behaviour (∼0.003–1 s−1). The response to the application of small constant shear stresses applied with a biconical disc in the bulk of the GSD was studied. In the region of shear thickening behaviour the GSD showed that the shear strain exhibited irregular fluctuations (i.e., rheological instabilities) about a steady-state value. The detrended fluctuation analysis (DFA) was used for characterising self-correlations and fractality of the measured time series. The computations showed that the irregular shear strain fluctuations contained long-term correlations that can be related to micro-structural features of the GSD. Besides, the strength of the long-term self-correlations increased with the applied shear stress, suggesting that the rheological instabilities can be attributed to elastic turbulence as induced by the gel micro-components. Light microscopy indicated that the rheological instabilities can be related to spatial heterogeneities of starch granules and leaked amylose acting as the inter-particle viscoelastic material.

The Earth is exposed to a permanent rain of cosmic particles from outer space [1]. Most of the particles are fully ionised atomic nuclei, moving with relativistic energies. The bulk of them with energies up to 1017 eV originate within our Milky Way. They are most likely accel- erated in supernova remnants. Some particles have a thousand times higher energies, i.e., around 1020 eV. This corresponds to the kinetic energy of a tennis ball with a mass of 50 g and a velocity of 90 km/h

The antimicrobial activity of different extracts of Alternanthera caracasana. HBK against 11 bacterial strains and 1 yeast strain was evaluated. The ethyl acetate extract showed antimicrobial activity against Staphylococcus aureus., Staphylococcus epidermidis., Bacillus subtilis., Sarcina lutea., and one strain of Vibrio cholerae.. There was no antimicrobial activity against Candida albicans.. As a bioactive compound, 7-methoxycoumarin was identified.

Background Systemic Lupus Erythematosus (SLE) is a systemic inflammatory disease associated with genetic, environmental, hormonal and immunological factors. Vitamin D levels are nowadays considered as one possible factor associated with disease activity. Therefore, previous studies have analyzed vitamin D to the severity of SLE. Objectives To assess the Vitamin D status in paraguayan SLE patients and its association with disease activity. Methods An observational Trial has been performed on individuals diagnosed with SLE. Epidemiological, clinical and biochemical data have been recorded for each patient to study the association between vitamin D concentrations, the phospho-calcium metabolism parameters and disease activity. Quantitative determination of Vitamin D was perform using chemoluminescence ARCHITEC assay. Vitamin D status was interpreted as follows: deficiency ≤20 ng/ml and insufficiency 21–29 ng/ml. The statistical association tests were performed using linear (SLEDAI activity index) and logistic (Inactive/Mild vs Moderate/Severe) regressions. The epidemiological, clinical and biochemical variables were used as explanatory variables in these models.This study is a preliminary analysis of a trial supported by CONACYT (Paraguay) to investigate the role of vitamin D in patients diagnosed with SLE. Results We included 77 SLE patients, of whom 94.8% (73/77) were female. The average age of patients at the time of the study was 30.7±10.3 years. All patients received calcium supplements associated with vitamin D. The average vitamin D concentration was 32.2±12.10 ng /ml. 29.9% (23/77) of patients had vitamin D insufficiency and 13.0% had vitamin D deficiency. 94.8% (73/77) of the population had normal serum calcium and the total population had a normal phosphoremia. As for the dosage of PTH, it was found that 27.3% (21/77) have high values of PTH. 20.8% (16/77) of the patients had positive anti-DNA. Low C3 complement was observed in 30/77 (39%) and low C4 in 50/77 (64.9%) patients. The mean value of SLEDAI at the time of the study was 2.32±2.83. When we study the distribution of vitamin D concentration according to the disease activity (SLEDAI) a clear pattern is observed linking lower vitamin D concentrations with higher disease activity (Figure 1). Patients with lower vitamin D concentrations are more likely to have higher disease activity (OR 0.93, 95% CI 0.88–0.99;P-Value=0.059. The means and standard deviations of vitamin D depending on the SLEDAI activity index are provided in Table 1. Conclusions In this preliminary study of Paraguayan SLE patients, Vitamin D deficiency was frequent despite treatment with supplements. In addition, a clear association between SLEDAI and Vitamin D values was observed. The final analysis in a larger patient cohort will have to confirm these findings and clarify relation with disease activity. References Eloi M, Horvath DV, Ortega JC, Prado MS, Andrade LE, Szejnfeld VL, de Moura Castro CH. 25-Hydroxivitamin D Serum Concentration, Not Free and Bioavailable Vitamin D, Is Associated with Disease Activity in Systemic Lupus Erythematosus Patients. PLoS One. 2017 Jan 13;12(1). Disclosure of Interest None declared

The effects of persistent organic pollutants (POPs) on humans and biodiversity are multiple and varied. Nowadays environmentally-friendly pesticides are strongly preferred to POPs. It is noteworthy that the crop protection role of pesticides and other techniques, i.e. biopesticides, plant extracts, prevention methods, organic methods, evaluation of plant resistance to certain pests under an integrated pest management (IPM), could improve the risks and benefits which must be assessed on a sound scientific basis. For this directive it is crucial to bring about a significant reduction in the use of chemical pesticides, not least through the promotion of sustainable alternative solutions such as organic farming and IPM. Biopesticides are derived from natural materials such as animals, plants, bacteria, and certain minerals. Most of them are biodegradable in relatively short periods of time. On this regard, substances from Calceolaria species emerge as a strong alternative to the use of POPs. The American genus Calceolaria species are regarded both as a notorious weeds and popular ornamental garden plants. Some have medicinal applications. Other taxa of Calceolaria are toxic to insects and resistant to microbial attack. These properties are probably associated with the presence of terpenes, iridoids, flavonoids, naphthoquinones and phenylpropanoids previously demonstrated to have interesting biological activities. In this article a comprehensive evaluation of the potential utilization of Calceolaria species as a source of biopesticides is made. The chemical profile of selected members of the Chilean Calceolaria integrifolia sensu lato complex represents a significant addition to previous studies. New secondary metabolites were isolated, identified and tested for their antifeedant, insect growth regulation and insecticidal activities against Spodoptera frugiperda and Drosophila melanogaster. These species serve as a model of insect pests using conventional procedures. Additionally, bactericidal and fungicidal activity were determined. Dunnione mixed with gallic acid was the most active fungistatic and fungicidal combination encountered. Several compounds as isorhamnetin, combined with ferulic and gallic acid quickly reduced cell viability, but cell viability was recovered quickly and did not differ from that of the control. The effect of these mixtures on cultures of Aspergillus niger, Fusarium moniliforme, Fusarium sporotrichum, Rhizoctonia solani, and Trichophyton mentagrophytes, was sublethal. However, when fungistatic isorhamnetin and dunnione were combined with sublethal amounts of both ferulic and gallic acid, respectively, strong fungicidal activity against theses strains was observed. Thus, dunnione combined with gallic acid completely restricted the recovery of cell viability. This apparent synergistic effect was probably due to the blockade of the recovery process from induced-stress. The same series of phenolics (iridoids, flavonoids, naphthoquinones and phenylpropanoids) were also tested against the Gram-negative bacteria Escherichia coli, Enterobacter agglomerans, and Salmonella typhi, and against the Gram-positive bacteria Bacillus subtilis, Sarcinia lutea, and Staphylococcus aureus and their effects compared with those that of kanamycin. Mixtures of isorhamnetin/dunnione/kaempferol/ferulic/gallic acid in various combinations were found to have the most potent bactericidal and fungicidal activity with MFC between 10 and 50 μg/ml. Quercetin was found to be the most potent fungistatic single compound with an MIC of 15 µg/ml. A time-kill curve study showed that quercetin was fungicidal against fungi assayed at any growth stage. This antifungal activity was slightly enhanced by combination with gallic acid. The primary antifungal action of the mixtures assayed likely comes from their ability to act as nonionic surfactants that disrupt the function of native membrane-associated proteins. Hence, the antifungal activity of isorhamnetin and other O-methyl flavonols appears to be mediated by biophysical processes. Maximum activity is obtained when the balance between hydrophilic and hydrophobic portions of the molecules of the mixtures becomes the most appropriate. Diterpenes, flavonoids, phenylpropanoids, iridoids and phenolic acids were identified by chromatographic procedures (HPLC-DAD), ESI-MS, and NMR hyphenated techniques.

The new echelle spectrograph FLECHAS (Fibre Linked ECHelle Astronomical Spectrograph) is in operation at the Nasmyth-focus of the 0.9 m telescope of the University Observatory Jena. FLECHAS is equipped with a sensitive back-illuminated and midband coated CCD-detector, as well as with a calibration unit for flatfield and wavelength-calibration. The spectrograph covers the spectral range between about 3900 and 8100 A and exhibits a resolving power of R ∼ 9300. In this article all technical characteristics of FLECHAS are described and examples of the first astronomical observations obtained with the new instrument in July 2013 at the University Observatory Jena are presented, among them the first light spectra taken with FLECHAS, simultaneous imaging and spectroscopic observations, the determination of the detection limit of the instrument, the spectroscopy of stars of different spectral types and of faint extended objects, as well as the Li-line detection in the spectra of young solar-like stars. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)