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Resumen La poliartritis cronica se define como la presencia de sinovitis en 4 o mas articulaciones, durante un periodo superior a las 6 semanas. Es uno de los motivos de consulta mas frecuentes en reumatologia. Su diagnostico diferencial incluye diferentes enfermedades reumaticas, infecciosas, metabolicas y neoplasicas. El diagnostico precisa una historia clinica y una exploracion minuciosas, asi como el uso de pruebas complementarias en base a la sospecha predominante. Presentamos un algoritmo para el manejo diagnostico protocolizado de la poliartritis cronica.

NiO and Cr2O3 are transition metal oxides with a partially filled d electron band that supports p-type conduction. Both are transparent to the visible light due to optical absorption beginning at wavelengths below 0.4 μm and the creation of holes by metal vacancy defects. The defect and strain effects on the electronic characteristics of these materials need to be established. For this purpose, NiO and Cr2O3 thin films were deposited on unheated glass substrates by reactive DC sputtering from metallic targets. Their structural, morphological, optical and electrical properties were analyzed comparatively in the as-grown conditions (25 °C) and after heating in air at 300 °C or 500 °C. The cubic NiO structure was identified with some tensile strain in the as-grown conditions and compressive strain after heating. Otherwise, the chromium oxide layers were amorphous as grown at 25 °C and crystallized into hexagonal Cr2O3 at 300 °C or above also with compressive strain after heating. Both materials achieved the highest visible transmittance (72%) and analogous electrical conductivity (~10−4 S/cm) by annealing at 500 °C. The as-grown NiO films showed a higher conductivity (2.5 × 10−2 S/cm) but lower transmittance (34%), which were related to more defects causing tensile strain in these samples.

SnS and SnS2 are earth abundant layered semiconductors that owing to their optoelectronic properties have been proposed as materials for different photovoltaic, photosensing and photocatalytic applications. The intrinsic efficiency of these materials for such applications is driven by their charge transfer dynamics, which in turn depend on their electronic structure and the interaction of the molecular orbitals involved in the charge transfer process. In this publication, we provide a step-by-step description of the use of the core hole clock method to obtain orbital dependent charge transfer times for SnS2 and SnS down to the attosecond time scale. We use both S 1s and Sn 3d core holes, with natural core hole lifetimes of 1.3 fs and 300 as, as time references to obtain a complete picture of electron delocalisation times across the conduction band of both materials. Ultrafast electron delocalisation times, lower than 5 femtoseconds and as low as tens of attoseconds, are measured for electrons excited to the unoccupied molecular orbitals of both materials. SnS delocalisation times are found to be shorter than those for SnS2 for all probed molecular orbitals, with delocalisation times being more than an order of magnitude shorter for higher lying molecular orbitals. DFT calculations show that charge transfer dynamics are strongly influenced by the interlayer interaction within these materials. The slower delocalisation of electrons in SnS2 can be linked to the restricted out of plane spatial dispersion of the molecular orbitals in the conduction band and consequent limitation of the electron delocalisation pathways. The results presented in this paper highlight the high potential of combining the core hole clock method with high-level DFT calculations to study orbital dependent charge transfer in semiconductor materials for optoelectronic applications down to the attosecond scale.

Intermediate band semiconductors can increase the efficiency of photovoltaic solar cells via sequential absorption of photons in a wider range of the solar spectrum. The introduction of Cr substituting Ga atoms in the chalcopyrite CuGaS2 is proposed to create a suitable intermediate band, investigating the influence of the Cu/Ga ratio on the structural, morphological, optical, and electrical characteristics. For this purpose, CuxGaS2 and CuxGaCr0.1S2 thin films (with x ranging from 0.8 to 1.2) are prepared by modulated evaporation from elemental sources and analyzed comparatively by X-ray diffraction, Raman spectroscopy, atomic force microscopy, spectrophotometry, and Hall effect measurements. The incorporation of Cr produces an in-gap absorption that is independent of the Cu/Ga ratio. The mean crystallite size, surface roughness, and electrical conductivity increase with the Cu content in both CuxGaS2 and CuxGaCr0.1S2.

Purpose: The purpose of this article is to evaluate the safety of two regorafenib dose-escalation approaches in refractory metastatic colorectal cancer (mCRC) patients.Patients and methods: Patients with mCRC and progression during or within 3 months following their last standard chemotherapy regimen were randomised to receive the approved dose of regorafenib of 160 mg QD (arm A) or 120 mg QD (arm B) administered as 3 weeks of treatment followed by 1 week off, or 160 mg QD 1 week on/1 week off (arm C). The primary end-point was the percentage of patients with G3/G4 treatment-related adverse events (AEs) in each arm.Results: There were 299 patients randomly assigned to arm A (n = 101), arm B (n = 99), or arm C (n = 99); 297 initiated treatments (arm A n = 100, arm B n = 98, arm C n = 99: pop-ulation for safety analyses). G3/4 treatment-related AEs occurred in 60%, 55%, and 54% of patients in arms A, B, and C, respectively. The most common G3/4 AEs were hypertension (19, 12, and 20 patients), fatigue (20, 14, and 15 patients), hypokalemia (11, 7, and 10 pa-tients), and hand-foot skin reaction (8, 7, and 3 patients). Median overall survival was 7.4 (IQR 4.0-13.7) months in arm A, 8.6 (IQR 3.8-13.4) in arm B, and 7.1 (IQR 4.4-12.4) in arm C.Conclusions: The alternative regorafenib dosing schedules were feasible and safe in patients with mCRC who had been previously treated with standard therapy. There was a higher nu-merical improvement on the most clinically relevant AEs in the intermittent dosing arm, particularly during the relevant first two cycles. Clinicaltrials.gov identifier: NCT02835924.(C) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

We study the joint determination of the lag length the dimension of the cointegrating space and the rank of the matrix of short-run parameters of a vector autoregressive (VAR) model using model selection criteria. We consider model selection criteria which have data-dependent penalties for a lack of parsimony, as well as the traditional ones. We suggest a new procedure which is a hybrid of traditional criteria with data-dependant penalties. In order to compute the fit of each model, we propose an iterative procedure to compute the maximum likelihood estimates of parameters of a VAR model with short-run and long-run restrictions. Our Monte Carlo simulations measure the improvements in forecasting accuracy that can arise from the joint determination of lag-length and rank, relative to the commonly used procedure of selecting the lag-length only and then testing for cointegration.

SnO is an ideally suitable p-type conductive material, with large hole mobility, and has attracted great interest in connection with next-generation electronic applications. In the present work, tin oxide (SnOx) thin films were deposited on unheated soda lime glass substrates by reactive DC sputtering from a pure Sn target. The structural, optical and electrical properties of the films were analysed as a function of the oxygen partial pressure in the sputtering atmosphere and of the post-deposition annealing temperature in air. A structural analysis was carried out using Raman spectroscopy and X-ray diffraction. Optical and electrical characterizations were performed using photo-spectrometry and Hall effect measurements, respectively. The films grown at room temperature and low oxygen pressures reached high deposition rates of above 45 nm/min, showing poorly crystalline SnO and low transparency. Subsequent heating to 350 °C allowed to achieve a more crystalline tetragonal SnO with an average visible transmittance of 65%, a p-type conductivity of 0.8 S/cm, and a hole mobility of 3.5 cm2/(V s).

SnO2 thin films are considered cheap transparent electrodes, interesting for scalable electronic applications, with intrinsic n-type conductivity related to donor defects like tin interstitials and oxygen vacancies. Besides, SnO2 allows n-type extrinsic doping by pentavalent cations such as Ta or Sb. In the present work, SnO2 and SnO2:Sb films were deposited on unheated soda lime glass substrates by reactive DC sputtering from Sn and Sn:Sb(5%) targets. Their structural, optical and electrical properties have been analyzed comparatively for the layers prepared at different oxygen partial pressures in the sputtering atmosphere, as-grown and after heating in air at several temperatures. Sb doping is proven effective to improve the electrical conductivity of sputtered tin dioxide samples. The contribution of oxygen vacancies is found dependent on the reactive deposition environment, in both pure and Sb-doped films, but subsequent heating can change the proportion and nature of the donor defects. For operation at temperatures above 400 °C, SnO2:Sb shows the best electrical performance and good thermal behavior is also achieved with pure SnO2 layers by adjusting the oxygen content in the sputtering atmosphere.

Resumen La morfea postradioterapia es una entidad poco frecuente descrita mayoritariamente en mujeres con cancer de mama. El uso creciente de la radioterapia en el tratamiento del cancer de mama, asi como la similitud clinica de la morfea con otros cuadros tales como la radiodermitis, la fibrosis postradiacion o la recidiva tumoral, obligan al dermatologo al conocimiento de esta entidad. Presentamos una serie de 6 mujeres, con una media de edad de 64,2 anos y un tiempo medio de latencia entre la radioterapia y la morfea de 9,5 anos. Cuatro de las 6 pacientes presentaban algun trastorno de base autoinmune (artritis reumatoide, sindrome de Sjogren, vitiligo y enfermedad de Crohn) entre sus antecedentes. Hasta el momento actual no se han encontrado factores de riesgo que predispongan al desarrollo de morfea tras el tratamiento con radioterapia, si bien parece que presentar algun trastorno de base autoinmune puede condicionar la aparicion de morfea en pacientes tratados con radioterapia.

Phononic Crystals (PnCs) are novel synthetic periodic materials for controlling and manipulating the propagation of elastic (or acoustic) waves. In this work, we have considered systems formed by three-dimensional (3D) acoustic rectangular waveguides, which have internal periodic structures. Also, the case of a two-dimensional (2D) rectangular waveguide with a periodic array of circular cylindrical inclusions is exhibited, to carry out a comparative study with the 3D case. Integral numerical methods used to obtain phononic band structures involve a Boundary Element Method, which requires the use of periodic Green’s functions. An interesting detail that resulted from this study was the appearance of band gaps of the proposed structure for different values of the filling fractions. The system considered constitutes itself a PnC whose band structure corresponds in many ways to a conventional one-dimensional PnC. This fact is an alternative to manufacture a PnC that exhibits a double function: acting as a PnC and as an acoustic waveguide. The main result of this work is that discrete modes for some frequency range were obtained, which indicates that Phononic Crystal Waveguides (PnCWs) considered act as unimodal filters when the filling fraction is large. These properties exhibit some interest from a technological point of view. Keywords: Phononic Crystal Waveguide, Periodic Green’s Function Method, Band gap, Discrete mode

INTRODUCTION: Post intubation tracheal rupture is very uncommon but has a great associated morbidity and mortality. Its incidence varies widely between publications and is estimated around 5/100.000 with standard tracheal tube (STT) and around 500-1900/100.000 with double lumen tube (DLT), although probably underestimated. Despite its relatively low incidence, airway management is paramount and could get extremely complex. CASE DESCRIPTION: Previously healthy 36 years old woman admitted at the ICU with bilateral pneumonia and respiratory insufficiency. Intubation and mechanical ventilation were required. Over the next 6 hours the patient status deteriorates and develops subcutaneous emphysema, pneumothorax and pneumomediastinum with hemodynamic instability. An emergency CT informs of a subcarinal tracheal rupture. With these findings and the general state worsening, a surgical approach is taken. Upon patient's arrival in the operating room, high inspiratory pressures are required and persistent aerial leak in the ventilator system is detected. Peripheral pulse oxymetry stabilizes around 88%. A fibrobronchoscopy is performed to advance the tube cuff lower from the rupture, but it fails as the trachea is filled with blood and dense mucus. As an alternative, the STT is switched with a left 35 Fr DLT with an exchanger in the means of isolating left bronchus and proceed with the surgery. After successfully isolating the left bronchus and positioning the patient for surgery, the DLT migrates and progressive oxygen desaturation and hemodynamic instability follow (with pulse oximetry below 30%, severe bradycardia and hypotension). It is in this critical moment that a 5mm STT is handed to the surgeon to pass it through the rupture thus isolating the left bronchus and allowing ventilation and reversing the critical state. After stabilization and in lateral decubitus, GlideScope was used to advance a 7,5mm STT to the tracheal rupture, where it was grasped and manually advanced to the left bronchus by the surgeon. This allowed effective ventilation and the reparation of the tracheal rupture. DISCUSSION: In the context of the COVID-19 pandemic, tracheal complications are on the rise due to prolonged intubation and ventilation times. Although infrequent, tracheal rupture is an extreme example of emergency airway management. This particular case required an unconventional approach as previous measures to te the airway had failed. Diagnosis should be confirmed through fiberoptic bronchoscopy and given the size of the rupture and patient's hemodynamic instability, if performed earlier, it could have given a definitive diagnosis and prevented further instability by advancing the STT bypassing the injury.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Background We explored the influence of BRAF and PIK3CA mutational status on the efficacy of bevacizumab or cetuximab plus 5-fluorouracil/leucovorin and irinotecan (FOLFIRI) as first-line therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC). Patients and methods VISNÚ-2 was a multicentre, randomised, phase II study. Patients with RAS wild-type mCRC and 1), and allocated to bevacizumab (5 mg/kg every 2 weeks) or cetuximab (400 mg/m2 then 250 mg/m2 weekly) plus FOLFIRI [irinotecan 180 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 (bolus) then 2400 mg/m2 (46-h continuous infusion) every 2 weeks]. The primary endpoint was progression-free survival (PFS). All analyses were exploratory. Results Two hundred and forty patients with BRAF/PIK3CA wild-type (n = 196) or BRAF- and/or PIK3CA-mutated tumours (n = 44) were enrolled. Median PFS was 12.7 and 8.8 months in patients with BRAF/PIK3CA wild-type and BRAF/PIK3CA-mutated tumours, respectively [hazard ratio (HR) = 1.22; 95% confidence interval (CI) 0.80-1.85; P = 0.3602]. In the BRAF- and/or PIK3CA-mutated cohort, median PFS was 2.8, 8.8 and 15.0 months in patients with BRAF/PI3KCA-mutated (n = 8), BRAF-mutated/PI3KCA wild-type (n = 16) and BRAF wild-type/PI3KCA-mutated (n = 20) tumours, respectively (P = 0.0002). PFS was similar with bevacizumab plus FOLFIRI versus cetuximab plus FOLFIRI in BRAF/PIK3CA wild-type (HR = 0.99; 95% CI 0.67-1.45; P = 0.9486) and BRAF/PIK3CA-mutated tumours (HR = 1.11; 95% CI 0.53-2.35; P = 0.7820). The most common grade 3/4 treatment-related adverse events were neutropenia, diarrhoea and asthenia in both treatment groups. Conclusions BRAF/PIK3CA status influences outcomes in patients with RAS wild-type mCRC but does not appear to assist with the selection of first-line targeted therapy, This work was supported by Roche Farma S.A (no grant number). Medical writing support was funded by Roche Farma S.A and provided by H. Lamb and L. Miller of Miller Medical Communications Ltd.

In 2016, Venezuela faced a large diphtheria outbreak that extended until 2019. Nasopharyngeal or oropharyngeal samples were prospectively collected from 51 suspected cases and retrospective data from 348 clinical records was retrieved from 14 hospitals between November 2017 and November 2018. Confirmed pathogenic Corynebactrium isolates were biotyped. Multilocus Sequence Typing (MLST) was performed followed by next-generation-based core genome-MLST and minimum spanning trees were generated. Subjects between 10 and 19 years of age were mostly affected (n = 95; 27.3%). Case fatality rates (CFR) were higher in males (19.4%), as compared to females (15.8%). The highest CFR (31.1%) was observed among those under 5, followed by the 40 to 49 age-group (25.0%). Nine samples corresponded to C. diphtheriae and 1 to C. ulcerans. Two Sequencing Types (ST), ST174 and ST697 (the latter not previously described) were identified among the eight C. diphtheriae isolates from Carabobo state. Cg-MLST revealed only one cluster also from Carabobo. The Whole Genome Sequencing analysis revealed that the outbreak seemed to be caused by different strains with C. diphtheriae and C. ulcerans coexisting. The reemergence and length of this outbreak suggest vaccination coverage problems and an inadequate control strategy. Open Access funding enabled and organized by Projekt DEAL. This work was supported by the Bernhard Nocht Institute for Tropical Medicine, Department of Infectious Disease Epidemiology budget not related with any particular grant. Sí

BackgroundIn subacromial pain syndrome, the supraspinatus tendon is the most frequently injured. Supraspinatus tendinosis is a structural lesion of the tendon stroma whose ultrasound diagnosis depends largely on the observer. Due to this, the follow-up is mainly clinical, based on ordinal scales of pain or mobility.The computer analysis of the image has been recently integrated into the musculoskeletal pathology, but the evidence in ultrasound is very limited.ObjectivesTo evaluate the computer analysis of the ultrasound image of the supraspinatus tendon at diagnosis and during evolution depending on the treatment administered.MethodsA retrospective study was carried out based on the ultrasound records of patients diagnosed with supraspinatus tendinosis between 2014 and 2020. All images were obtained with the same ultrasound equipment. The records had to fulfill the following characteristics: (i) Absence of direct or indirect ultrasound signs of fibrillar continuity solution, (ii) absence of calcifying lesions and (iii) availability of an ultrasound study 5-7 months after diagnosis with the same frequency, gain, and depth parameters for each case.The ultrasound images showing tendinosis were analyzed using the ImageJ 1.53e program. The means and modes of the grayscale signal intensities were determined in longitudinal and transverse projection for each image.For the statistical analysis, paired before-after comparisons based on the normal distribution were used, grouping the patients according to the injured tendon area (lateral, central, medial) and the treatment administered. To determine the weight of the variables analyzed in the probability of resolution, a forward modeled binary logistic regression was performed using the Wald method.ResultsRecords of 35 patients were included: 10 treated with immobilization, 12 with corticosteroid injections and 13 with physical therapy. Table 1 summarizes the demographic and clinical characteristics of the population.Table 1.Demographic and clinical characteristics of the population. GI: gray intensity according to longitudinal or transverse axis. SD: standard deviation.Treatment groupPhysical therapyImmobilizationInjectionsMeanSDN (%)MeanSDN (%)MeanSDN (%)Age55854105610SexWomen11 (84,6%)7 (70%)9 (75%)Men2 (15,4%)3 (30%)3 (25%)Injured areaCentral1 (7,7%)0 (0%)1 (10%)0 (0%)Lateral5 (38,5%)3 (30%)3 (25%)Medial7 (53,8%)6 (60%)9 (75%)GI Long axis.79,20920,12769,95314,81582,21333,638GI Trans axis81,84017,29174,09119,6393 (25%)85,99134,520The changes observed in the mean gray intensity in the longitudinal projection of the tendon did not correlate with the fact that the patients were discharged (0.006 SD 10.47) or not (2.231 SD 7.8835) after the second evaluation (t=-0.708, P=.484). In contrast, the gradient of the mean gray intensity in the transverse projection of the tendon showed significant differences between patients discharged (9.268 SD 3.752) or not (-0.2054 SD 5.26), (t=6.162, P=.000). On the other hand, in the group of patients discharged, a greater reduction was observed in the dispersion of the mean gray intensities (-11.08 SD 5.843) compared to the group that was not discharged (1.178 SD 1.859), (t=-8.458, P=.000).In the multivariate logistic regression analysis, only the final dispersion of gray intensity was associated with the discharge condition with Coef. B=-0.096, P=.027, HR 0.908 (95% CI: 0.834-0.989).ConclusionComputer analysis of ultrasound images of the supraspinatus tendon in patients with pure structural tendinosis distinguishes a favorable clinical course only in the study of the cross-sectional projection, probably due to the more flattened shape of the tendon.Clinical resolution, understood as medical discharge after the second evaluation, is associated with an increase in the mean intensity of grays but especially with a reduction in the dispersion of grays.Disclosure of InterestsMarina Tortosa-Cabañas: None declared, Carlos Guillén-Astete Speakers bureau: Novartis, Janssen, Abbvie, Grunenthal, UCB and Gebro, Paid instructor for: Roche, Novartis, Janssen, Esteve and Menarini, Consultant of: Janssen, Novartis and Roche, Grant/research support from: Pfizer, Grunenthal, Gebro and Novartis, África Andreu-Suárez: None declared

BackgroundThe ultrasound study of tendons is a component of the complementary evaluation of patients with different musculoskeletal pathologies, which include immune-mediated rheumatological diseases. Until now, the assessment of the ultrasound status of the tendons largely depends on the subjectivity of the explorer, following specific guidelines such as the fibers structure, their global echogenicity and their thickness. This evaluation is of great interest for the diagnose, however its role for the follow-up is not so clear as the subjective evaluation may not perceive subtle changes.Computerized image analysis has recently been introduced to complement the echographic evaluation. Two of the most useful parameters in this analysis are the mean and mode of gray intensities. Both allow a global evaluation of the echostructure of an organ based on the distribution of shades of gray and the highest concentration of a particular shade, without evaluating the organization pattern of the image obtained.ObjectivesTo determine if computer analysis of static images is valid and suitable for its use in the study of tendons.MethodsThe ultrasound images of healthy volunteers were analyzed. The analysed tendons were: the body of the patellar tendon in transverse approach and the longitudinal section of the Achilles tendon, both of them from the dominant side. Image processing was performed using the ImageJ 1.53e program (Wayne Rasband & contributors – NIH, USA). A gray spectrum analysis (0-255) was performed with the calculation of the mean, standard deviation (SD), range, median and mode. Two measurements of different cuts of the patellar tendon (at the point of emergence of the tibial plateau and 20 mm proximal to it) and three longitudinal cuts of 20 mm of the Achilles tendon (paramedial, central and paralateral) were used for the validation process of the analysis carried out by the software.ResultsImages from 44 healthy volunteers were analyzed: 20 men and 24 women. 44 Achilles tendon image trios and 44 patellar tendon image pairs were analyzed and their corresponding means and modes were compared as related variables. In the study of the Achilles tendon, according to the Shapiro-Wilk test, the distribution of the gray distribution means had a non-normal distribution while the modes had a normal distribution. The means ± standard deviation of gray intensity was: 80.15 ± 26.04, 80.05 ± 25.57 and 79.91 ± 25.83 for the medial, central and lateral slices, respectively (Friedman, P=.454; Bonferroni not applicable). The means of the modes of gray intensities for the same measures were 67.35 ± 31.60, 67.76 ± 32.18 and 68 ± 32.18, respectively (ANOVA paired data, P=.259; Bonferroni not applicable). In the patellar tendon study, all measurement distributions were non-normal. Mean gray intensity at the point of tendon emergence (P) was 81.35 ± 29.63 and at 20mm proximal to this point it was 80.97 ± 29.08 (Wilcoxon, P=.327). The means of the modes at the same locations were 82.71 ± 28.75 and at 20mm proximal to this point it was 64.44 ± 33.31 (Wilcoxon, P=.079).Figure 1.Image analysis of an Achilles tendon in the central longitudinal plane.ConclusionThe quantitative analysis of static images of healthy tendons shows no differences between the same structures in longitudinal or transverse planes.Based on this validation test, the demonstration of sensitivity to change caused by any stimulus (sport, noxae or treatments) could allow its use as a complementary instrument for the assessment of tendinous structures over time.Disclosure of InterestsÁfrica Andreu-Suárez: None declared, Carlos Guillén-Astete Speakers bureau: Novartis, Janssen, Abbvie, Grunenthal, UCB, Gebro, Paid instructor for: Roche, Novartis, Janssen, Esteve, Menarini, Consultant of: Janssen, Novartis, Roche, Grant/research support from: Pfizer, Grunenthal, Gebro, Novartis, Marina Tortosa-Cabañas: None declared

BackgroundEnthesitis is the base of the pathophysiology of spondyloarthritis. Recently, our group has shown that computer analysis of static images can be used in the evaluation of patients with enthesic inflammatory diseases with good intra-patient and intra-observer validity and sensitivity to change.ObjectivesTo determine the enthesic evolution in patients with spondyloarthritis (SpA) treated with three different biological therapies through the computer analysis of ultrasound images.MethodsWe selected patients diagnosed with SpA and enthesitis followed by imaging, who started biological therapy with a TNF inhibitor, an IL17 inhibitor or an IL12/23 inhibitor. For the records to be included, it was necessary to have clinical information from the period of perfoming the ultrasound. All images were obtained from the Achilles tendon, with the same ultrasound equipment, grayscale and settings for each patient.To homogenize the results of the analysis, the gray intensity mean index (iMIG) was used, which has been shown to appropriately discriminate the inflammatory pathology from the mechanical or healthy controls as well as being sensitive to change.Results14 patients were included: 6 treated with a TNF inhibitor, 4 with an IL17 inhibitor and 4 with an IL12/23 inhibitor. Patients 2, 3, 5, 7, 10, 11, and 12 had enthesophytes.In the global analysis, the iMIG did not show statistically significant differences between the treatment groups at the start of the treatment, at the intermediate and at the final evaluation (P=.588, .739 and .674, respectively).Patients with enthesophytes presented significantly higher baseline, intermediate and final iMIG than patients without them: 1.26 SD 0.14 vs 0.85 SD 0.05 (t=7.407, P=.001), 1.24 SD 0.15 vs 0.97 SD 0.1 (t=3.659, P=.006); and 1.21 SD 0.12 vs 1.05 SD 0.07 (t=2.342, P=.037), respectively.Analyzing only the patients without enthesophytosis, the final iMIG showed statistically significant differences between the 3 administered treatments (ANOVA, F=8.142, P=.027), being relevant between the use of IL12/23 and TNF inhibitor in favor of the former (Bonferroni, P=.03).In the same subgroup of patients without enthesophytosis, iMIG analysis over time showed statistically significant differences between final and baseline iMIG (Friedman -1.938 P=.000).ConclusionComputer analysis of ultrasound images using the iMIG distinguishes therapeutic response in patients without enthesophytosis.The interposition of enthesophytes impede the correct visualization of the enthesis and does not allow ultrasound changes to be detected in some areas of the image.Although there are indications that the use of this analysis could also predict the behavior of certain therapies, it is convenient to propose prospective studies with homogeneous ultrasound controls.Table 1.List of patients included in the analysis. After the final ultrasound examination, the follow-up time up to the present is recorded in the case of continued treatment (m: months).TreatmentEnthesophytesBasal MIGBasal iMIGIntermediate examinationIntermediate iMIGFinal examinationFinal iMIGTreatment follow-up1TNFi71,4240,85+6m0,89+6m0,94Continues +24m2TNFi+156,4151,48+5m1,51+6m1,52Suspended for inefficacy (enthesitis)3TNFi+164,3231,32+6m1,34+6m1,35Suspended for inefficacy (enthesitis)4TNFi69,3210,78+4m0,80+6m0,94Suspended for inefficacy (axial pain)5TNFi+141,4731,14+6m1,19+4m1,18Suspended for inefficacy (enthesitis)6TNFi68,4830,85+3m1,03+5m1,05Continues +20m7iIL17+135,4321,34+5m1,26+4m1,15Continues +22m8iIL1772,2250,90+6m1,02+4m1,06Continues +20m9iIL1780,4650,89+3m1,03+6m1,03Suspended for inefficacy (arthritis).10iIL17+122,2541,16+6m1,11+4m1,04Continues +24m11iIL12/2371,4010,79+8m1,01+4m1,1Suspended for inefficacy (axial pain)12iIL12/23+134,411,12+6m1,08+6m1,07Continues +18m13iIL12/2375,420,94+4m1,12+6m1,16Continues +20m14iIL12/2369,1120,84+3m0,9+8m1,12Continues +18mDisclosure of InterestsMarina Tortosa-Cabañas: None declared, Carlos Guillén-Astete Speakers bureau: Novartis, Janssen, Abbvie, Grunenthal, UCB and Gebro, Paid instructor for: Roche, Novartis, Janssen, Esteve and Menarini, Consultant of: Janssen, Novartis and Roche, Grant/research support from: Pfizer, Grunenthal, Gebro and Novartis, África Andreu-Suárez: None declared

BackgroundThe computerized assessment of ultrasound images is an alternative to the dichotomous subjective assessment often used in the study of entheses. Previously, our group has demonstrated its usefulness in assessing greyscale images; however, the evaluation of enthesial hyperemia using this technique remains a pending task.Objectives-To determine the intra-observer and intra-patient variability of the hyperemia study using computer analysis of static images.MethodsPatients with a diagnosis of known spondyloarthritis and ultrasound enthesitis of the Achilles tendon -according to EULAR criteria (detection of hyperemia by power Doppler (PD) signal within 2mm of the cortex)- were selected. Longitudinal medial, central and lateral image sections were obtained. Hyperemia was assessed by PD signal detection, and the images with the highest signal intensity were recorded, maintaining the same doppler gain and PRF settings for each subject.For image analysis, recordings were coded and randomized so that the analyst did not know to which patient a given section corresponded. Intra-patient validity was assessed by comparing the results of sections from the same patient with each other at two different times. Intra-observer validity was evaluated by subjecting the same image to two computer analyses at different times. Finally, validation of sensitivity to change was performed by successive measurements. The software used was ImageJ 1.53e (NIH, USA).ResultsImages of 12 patients with Achilles enthesitis were included: 6 patients with SpA-nRx, four patients with PsA, and two patients with SpA-Rx.On intra-patient evaluation, significant differences in PD signal intensity were detected between medial, lateral, and central sections. In all cases, the measurement obtained in the central section was the highest (Friedman 15.500 P=.000; medial-central -1.500, P=.001; lateral-central -1.250, P=.007). The coefficient of variation in the first and second determinations without considering the sign of the variation was: 4.2% SD 5.5%.In the intra-observer evaluation of the PD signal evaluations at the central cut-off, the mean coefficient of variation, without considering the sign, was: 9.1% SD 7.2%.In assessing sensitivity to change, patients with 6-month ultrasound studies were grouped into those who maintained treatment and those who eventually discontinued treatment due to therapeutic failure. In the seven patients who maintained treatment, the mean change in hyperemic areas was -94.3% SD 4.4%, while in the five patients who discontinued treatment, it was -65.4% SD 6.3% (p=.000).Figure 1.Evaluation of the PD signal.ConclusionComputer analysis of static Achilles tendon images conforms to the same ultrasound image acquisition recommendations. In addition, it demonstrates excellent intra-patient and inter-observer variability and sensitivity to change, at least when correlated with therapeutic success or failure from a clinical perspective.Disclosure of InterestsCarlos Guillén-Astete Speakers bureau: Novartis, Janssen, Abbvie, Grunenthal, UCB, Gebro, Paid instructor for: Roche, Novartis, Janssen, Esteve, Menarini, Consultant of: Janssen, Novartis, Roche, Grant/research support from: Pfizer, Grunenthal, Gebro, Novartis, África Andreu-Suárez: None declared, Marina Tortosa-Cabañas: None declared

BackgroundSensitivity to change is the ability of a tool to detect changes in the measurement of a variable when this measurement is made on the same target over time. In the follow-up of patients with immune-mediated diseases, it is required that the instruments used to evaluate changes over time demonstrate enough precision. However, ultrasound studies stratify the results of the evaluations in ordinal degrees of intensity of findings dependent on the evaluator’s opinion.Computer analysis of static images has recently been introduced in the study of patients with rheumatic diseases. Nonetheless, its application in musculoskeletal ultrasound is still very limited.Objectives-To determine if this type of image analysis is sensitive to structural adaptive change of the patellar and Achilles tendons in healthy subjects.MethodsWe recruited young volunteers with a declared sedentary habit and with a normal BMI. They carried out a supervised physical exercise routine for 6 months.Two ultrasound measurements of the patellar and the Achilles long axis were performed. Also, two elastographies of the same tendons and two anthropometric measurements of the thigh and calf were made at the beginning and end of the training period.To demonstrate sensitivity to change, a correlation was made between the ultrasound, elastrographic and anthropometric morphological changes, and the result of the computer analysis of the image in terms of gray scale mean and mode.Results19 volunteers were evaluated (mean age 24 ±2 years, 12 women).After the exercise routine, we found statistically significant differences between calf perimeter (mean -3,70 ±1,803; p .000), Achilles elastography (-,347 ±,294; p .000), Achilles and patellar MGI (4,229 ±4,849; p .001 and 2,331 ±3,115; p,004). Regarding the non-normal distributed variables, we met statistically significant differences between patellar elastography (average range 11,45, sum of the ranks 126,00; Z -2,343; p,019), Achilles and patellar grey intensity modes (average 12,92, sum 168,00; Z -2,938; p,003 and average 11,77, sum 176,50; Z -3,28; p,001). The correlations study is shown in Table 1.Table 1.Results of the Pearson correlation tests of changes experienced over time.Variables of change (Final-Baseline)Achilles tendon elasticity changePatellar tendon elasticity changeAchilles mean grey intensity changesPatellar mean grey intensity changesAchilles mode grey intensity changesPatellar mode grey intensity changesCalf circumference changePearson correlation,050,470*,094,530*,935**,029Sig. (bilateral),840,042,701,020,000,907Thigh circumference changePearson correlation,014-,069,120-,160,022,904**Sig. (bilateral),956,780,624,514,928,000Body Fat % ChangePearson correlation-,237,098-,033,119-,091,011Sig. (bilateral),330,689,893,626,712,963Achilles tendon elasticity changePearson correlation1,221,779**,090,147-,032Sig. (bilateral),362,000,715,548,896Patellar tendon elasticity changePearson correlation,2211,353,899**,416-,154Sig. (bilateral),362,139,000,076,529Figure 1.Before (upper) and after (lower) evaluation.ConclusionComputer analysis of static images of the Achilles and patellar tendons is sensitive to the change induced by exercise in young and healthy subjects.The mean gray intensity correlates better with elastography. This shows that the predominance of the fibrillar pattern induced by exercise produces a higher speed of sound conduction. The gray intensity mode correlates better with the anthropometric changes experienced by the subjects. The concentration of shades in white extremes translates into greater anthropometric changes.This demonstrates that the stiffness or elasticity of a tendon correlates with the global distribution of gray. The response to mechanical stimuli correlates with the concentration of more intense white tones that are not necessarily scattered (endophytes or pre-enthesophytes).Disclosure of InterestsCarlos Guillén-Astete Speakers bureau: Novartis, Janssen, Abbvie, Grunenthal, UCB, Gebro, Paid instructor for: Roche, Novartis, Janssen, Esteve, Menarini, Consultant of: Janssen, Novartis, Roche, Grant/research support from: Pfizer, Grunenthal, Gebro, Novartis, África Andreu-Suárez: None declared, Marina Tortosa-Cabañas: None declared, Cristina Pijoan Moratalla: None declared, Paula Barrio Rufino: None declared, Esther Muñoz Rodriguez: None declared, Jorge Mollá Cuadrillero: None declared

BackgroundComputer analysis of radiological images has recently been introduced in the study of patients with musculoskeletal pathologies. In the field of ultrasound, baseline settings and differences between images obtained by different equipment pose a potential problem in the comparative study of patients.Our research group has shown that this type of ultrasound image analysis is sensitive to exercise-induced adaptive changes.ObjectivesThe purpose of this study is to determine if the computer analysis of entheses ultrasound images can distinguish adaptive changes from those produced by spondyloarthritis.MethodsA test validation study was carried out. Since the analysis of static ultrasound images strongly depends on the characteristics of the image and the ultrasound settings, three indices based on the findings in pathological territories and their counterpart in healthy entheses were defined.Gray Intensity Mean Index (iMIG): Mean gray intensity in the clinically affected enthesis/mean gray intensity in the same healthy enthesis.Gray intensity dispersion index (iDIG): Mean of the standard deviation of the gray intensity means in the clinically affected enthesis/mean of the standard deviation of the gray intensity means in the same healthy enthesis.Index of gray intensity modes (iMoG): Mean gray intensity modes in the affected enthesis/mean gray intensity in the same healthy enthesis.The same indices were used in the controls with the dominant side as the numerator and the non-dominant side as the denominator.All the studied entheses corresponded to the lower limb.ResultsRecords of 49 patients (20 diagnosed with psoriatic arthritis, 19 with radiographic axial spondyloarthritis and 10 with non-radiographic axial spondyloarthritis) and 100 healthy controls were included. Of the 49 studies, 30 corresponded to the Achilles tendon, 10 to the distal patellar tendon and 9 to the proximal patellar tendon.In the patient group, iMIG was 0.917 SD 0.062, iDIG was 0.976 SD 0.042, and iMoIG was 0.962 SD 0.041. In the control group, iMIG 1 SD 0.020, iDIG was 1.001 SD 0.03, and iMoIG was 0.999 SD 0.03.The area under the curve (Figure 1) for the three indices was: iMIG 0.879 (95% CI 0.807 to 0.951), iDIG (95% CI 0.582 to 0.785), iMoIG 0.751 (95% CI 0.662 to 0.840). All areas demonstrated diagnostic validity with PFigure 1.ROC curves for the three analyzed indices.According to the matrix of coordinates of the receiver-operating-characteristic (ROC) curve, for an iMIG cut-off point less than or equal to 1.02, a sensitivity of 95.9% and a specificity of 71% would be achieved.ConclusionThe indices that contrast the means, dispersion and mode of gray intensities are valid for discriminating between healthy subjects and patients with load-bearing enthesopathies related to spondyloarthritis. Of all of them, the iMIG seems the most reliable. A cut-off point of less than 1.02 is proposed to identify patients with inflammatory enthesopathies.In patients, the affected entheses have a lower mean gray than the healthy counterpart, so iMIG tends to be less than 1. In healthy subjects, the mean gray is slightly higher in the dominant enthesis, so iMIG tends to be greater than or equal to 1.Disclosure of InterestsMarina Tortosa-Cabañas: None declared, Carlos Guillén-Astete Speakers bureau: Novartis, Janssen, Abbvie, Grunenthal, UCB and Gebro, Paid instructor for: Roche, Novartis, Janssen, Esteve and Menarini, Consultant of: Janssen, Novartis and Roche, Grant/research support from: Pfizer, Grunenthal, Gebro and Novartis, África Andreu-Suárez: None declared

BackgroundIt has recently been demonstrated that computer analysis of static ultrasound images can detect exercise-induced stromal changes in the body’s load-bearing tendons.ObjectivesThe purpose of this study is to determine if the same analysis can detect enthesic changes in patients who have undergone corticosteroid infiltration in the preachilles bursa.MethodsSerial images of patients who received corticosteroid injections (around 40mg of triamcinolone acetonide) in the preachilles bursa were selected. For the records to be considered it was necessary at least one baseline ultrasound study, one between the first and second month after the injection and one between the third and sixth month after the injection.All images were obtained with the same ultrasound equipment, by the same operator and with the same gain and frequency settings.The images were analyzed using the ImageJ 1.53e program, which allowed the recording of the mean intensity of gray (MIG), dispersion of gray intensities (DIG) and mode of gray intensities (MoIG).ResultsEighteen image collections from the same number of patients were selected. Eight corresponded to mechanical enthesopathies (without any diagnosis of spondyloarthritis) and ten were patients with a diagnosis of axial spondyloarthritis (5) or psoriatic arthritis (5).The ratios of MIG, DIG and MoIG of the injured enthesis with respect to its control were, respectively, 1.12 SD 0.14, 0.88 SD 0.42 and 2.04 SD 1.54 for the mechanical pathology group and 0.89 SD 0.05, 1 SD 0.04 and 0.96 SD 0.03 for the inflammatory pathology group. Statistically significant differences in the MIG ratio were detected between patients with inflammatory diseases and patients with mechanical injuries (t=4.69, P=.000).Among patients with inflammatory pathology, the change between baseline and 3-6 months after infiltration MIG was statistically significant (82.59 SD 37.68 vs 92.02 SD 38.67; t=-5.69, P=.000). The changes between DIG and MoIG were not significant (t=0.899, P=.392 and t=-1.542, P=.158, respectively). Among patients with mechanical pathology, there were no significant differences between final and baseline MIG, DIG, or MoIG (t=1.921, P=.096; t=-1.533, P=0.169; and t=1.761, P=0.122, respectively).Figure 1 summarizes the changes in the mean gray intensity index (iMIG) in patients with mechanical and inflammatory pathology. In patients with inflammatory diseases, the changes between the final and basal iMIG tend to normalize (approaching the unit). In the mechanical pathology group, the iMIG variation shows a less defined behavior.Figure 1.Box and whisker plot showing the evolution over time of the pathological/healthy gray intensity mean coefficient. MIGp: Mean gray intensity in the pathological enthesis. MIGc: Mean gray intensity in the control enthesis of the same patient.ConclusionThe computer analysis of static images in gray scale can detect the changes observed in the Achilles enthesis of patients with inflammatory diseases such as spondyloarthritis. It is also demonstrated that in these patients the gray intensity change rate tends to be normalized (approaching the unit) after a steroid injection.Trend to normalization has not been evidenced in patients with mechanical pathology. Corticosteroids apparently do not act on the origin of the mechanical enthesopathies. Therefore, the study of the average, dispersion and fashion of gray intensities is erratic.The capacity of MIG detecting evolutionary changes in inflammatory pathology shows a potential for the follow-up of patients with spondyloarthritis and entheseal commitment.Disclosure of InterestsCarlos Guillén-Astete Speakers bureau: Novartis, Janssen, Abbvie, Grunenthal, UCB and Gebro., Paid instructor for: Roche, Novartis, Janssen, Esteve and Menarini., Consultant of: Janssen, Novartis and Roche., Grant/research support from: Pfizer, Grunenthal, Gebro and Novartis., Marina Tortosa-Cabañas: None declared, África Andreu-Suárez: None declared

Transparent heat reflectors have been prepared by DC sputtering of pure metal targets on glass substrates at room temperature. These are three-layer coatings based on a high reflective silver film surrounded by transparent tin oxide layers, which reduce greatly the silver reflection in the visible range, but not in the infrared region. In fact, such infrared reflectance has been controlled by the Ag interlayer thickness. Besides, during the tin oxide growth by reactive deposition, both the oxygen partial pressure and the sputtering time have been tuned to maximize the visible transmission while avoiding the possible Ag oxidation. In this way, optimized SnOx/Ag/SnOx coatings have been achieved with high luminous transmittance (τL = 81% including the glass substrate) and low solar heat gain (g = 0.55), as required for energy-efficient glazing applications.

espanolEl paisaje cultural de las minas de Mazarron representa una realidad tangible forjada entre el hombre y la naturaleza a lo largo de diferentes secuencias historicas. Su capital simbolico esta situado en un territorio que ha sido intensamente modificado por el dinamismo productivo y forma parte indisociable del imaginario colectivo de la poblacion. En este articulo analizamos los avatares que ha sufrido este singular paisaje desde que concluyo su actividad industrial en la decada de los anos 60 del pasado siglo XX, hasta hoy. Denunciamos la escasa o nula sensibilidad que han tenido las administraciones publicas para ponerlo en valor, los incesantes ataques a su preservacion desde todas partes y los dificiles problemas que tiene actualmente sin resolver. English EnglishThe cultural landscape of the Mazarron mines represents a tangible reality forged between man and nature along different historical sequences. Its symbolic capital is located in a territory that has been intensely modified by the productive dynamism and forms an inseparable part of the collective imaginary of the population. In this article we analyze the avatars that this singular landscape has suffered since its industrial activity ended in the decade of the 60’s of the last century, until today. We denounce the little or no sensitivity that the public administrations have had to put them in value, the incessant attacks on their preservation from all sides and the difficult problems that are currently unresolved

Introduction and objectives Vismodegib is the first selective Hedgehog inhibitor approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). In this article, we describe our experience with the use of this drug to treat advanced and/or multiple BCCs at a cancer center over 5 years. Material and methods We analyzed the following variables: patient age and sex; tumor location, size, type, and characteristics; time since onset; primary or recurrent status; duration of treatment; response to treatment (complete, partial, stabilization, or absence of response); adverse effects; and recurrences. Results We treated 22 patients, of whom 20 had locally advanced BCCs and 2 had metastatic BCCs with lymph node involvement. The treatment was administered over a mean of 11.8 months. Nine patients (41%) achieved complete response and 10 (45%) partial response. The disease was stabilized in 3 (14%). Two patients relapsed after a median of 21 months. The main adverse effects were dysgeusia, alopecia, and muscle cramps, all of which were mild. None of the patients developed squamous cell carcinoma in an area treated with vismodegib, although metatypical changes were observed after treatment. Conclusions With a response rate of 96%, vismodegib is a safe and effective treatment for locally advanced BCC. Adverse effects are generally mild but they need to be taken into account owing to their high frequency.