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Thermoregulating composites were produced by using a thermoregulating slurry (NPCS) containing nanoencapsulated phase change material (NPCM) from poly(styrene-co-divinylbenzene) as shell and the commercial paraffin Rubitherm®RT27 as core material. These composites were synthesized by using the constitutive water of the slurry as setting water and changing the NPCM/Hemihydrate (NPCM/Hem) mass ratio within 0.0–0.41. It was found that nanoparticles were uniformly dispersed into the gypsum, and the gypsum crystal morphology was tuned by the addition of the slurry. Attending to the thermal properties, these materials can work either as insulating or thermal energy storage materials, decreasing the thermal conductivity up to ~ 50%, whereas the thermal energy storage (TES) capacity is enlarged in a ~ 140%, respect to the pure gypsum, when the maximum NPCM/Hem mass ratio was used. This composite had a latent heat of 30.2 J g−1 and a heat capacity of equivalent 3.5 J g−1 K−1. Composites from a NPCM/Hem mass ratio up to 0.15 satisfied European mechanical standard EN 13,279–1 for gypsum binders and gypsum plasters and all of them, presented a bulk density higher than 0.60 g cm−3. The addition of a 41% in mass of nanocapsules allowed to save 13.5 kWh m−3 and, reducing the CO2 emissions up to 3.4 kg of CO2 per operating cycle. The use of this new material would lead to significant energy and economic savings, as well as a considerable reduction in the emission of polluting gases into the atmosphere., Los compuestos termorreguladores se produjeron utilizando una suspensión termorreguladora (NPCS) que contenía material de cambio de fase nanoencapsulado (NPCM) de poli(estireno-co-divinilbenceno) como cubierta y la parafina comercial Rubitherm®RT27 como material central. Estos compuestos se sintetizaron usando el agua constitutiva de la suspensión como agua de fraguado y cambiando la relación de masa NPCM/Hemihidrato (NPCM/Hem) entre 0,0 y 0,41. Se encontró que las nanopartículas se dispersaron uniformemente en el yeso, y la morfología del cristal de yeso se ajustó mediante la adición de la suspensión. Atendiendo a las propiedades térmicas, estos materiales pueden funcionar como materiales aislantes o de almacenamiento de energía térmica, disminuyendo la conductividad térmica hasta ~ 50%, mientras que la capacidad de almacenamiento de energía térmica (TES) se amplía en un ~ 140%, respecto a la pura. yeso, cuando se utilizó la máxima relación de masa NPCM/Hem. Este material compuesto tenía un calor latente de 30,2 J g−1 y una capacidad calorífica equivalente a 3,5 J g−1 K−1. Los composites a partir de una relación másica NPCM/Hem hasta 0,15 cumplieron con la norma mecánica europea EN 13.279–1 para aglomerantes de yeso y revoques de yeso y todos ellos, presentaron una densidad aparente superior a 0,60 g cm−3. La adición de un 41% en masa de nanocápsulas permitió ahorrar 13,5 kWh m−3 y, reducir las emisiones de CO2 hasta 3,4 kg de CO2 por ciclo de operación. La utilización de este nuevo material supondría un importante ahorro energético y económico, así como una considerable reducción de la emisión de gases contaminantes a la atmósfera.

[Background The aim of this study was to evaluate the impact of certain single-nucleotide polymorphisms (SNPs) in cabazitaxel activity and tox]icity in patients with metastatic castration-resistant prostate cancer (mCRPC)., [Patients & methods] 56 SNPs in five genes (CYP3A4, CYP3A5, ABCB1, TUBB1 and CYP2C8) were genotyped in 67 mCRPC patients and their correlation with outcomes analyzed., [Results]TUBB1-rs151352 (hazard ratio: 0.52) and CYP2C8-rs1341164 (hazard ratio: 0.53) were associated with better overall survival, and CYP2C8-rs1058932 with biochemical progression (odds ratio: 6.60) in multivariate analysis. ABCB1-rs17327624 correlated with severe toxicity ≥grade 3 (odds ratio: 8.56) and CYP2C8-rs11572093 with asthenia (odds ratio: 8.12)., [Conclusion] Genetic variants in mCRPC patients could explain different outcomes with cabazitaxel. Nonetheless, the small sample size and the high number of SNPs analyzed mean that the results are only hypothesis-generating and require further validation.

Dissociation is a complex phenomenon which is present in a wide variety of psychiatric disorders and also in the general population. The objective of this study was to examine the relationship between childhood and adolescent traumas and development of dissociative phenomena in a nonclinical population, emphasizing the potentially mediating role of rumination, intrusive thoughts and negative affect in a population with no psychiatric pathology in adulthood. The sample was comprised of 337 participants from the general population (58.8% women) with a mean age of 33.10 years (SD: 14.08). They completed the Juvenile Victimization Questionnaire (JVQ), the Ruminative Response Scale (RRS), the White Bear Suppression Scale (WBSI), the Dissociative Experience Scale, 2d ver. Rev. (DES-II) and the Depression, Anxiety and Stress Scale (DASS-21). The results supported the starting hypotheses showing a positive correlation between childhood and adolescent trauma and dissociation, and between childhood and adolescent trauma and rumination, intrusive thoughts and negative affect, and mediation of these variables between childhood and adolescent trauma and dissociative states. The relationship between trauma in early ages and dissociation in adulthood is complex. Although the design used in this study was cross-sectional, the results are compatible with the starting hypothesis that rumination, intrusive thoughts and negative affect mediate this relationship.

Ideas of reference (IR) - self-attributions about what happens in the social environment are a frequent phenomenon present in a wide variety of people with mental health disorders as well as in the nonclinical population. The purpose of this study was to find out the relationship between traumatic childhood experiences, IR and dissociative states in the nonclinical population, emphasizing the potential mediating role of dissociation between traumatic experiences and IR. The sample was comprised of 337 participants from the general population (58.8% women) with a mean age of 33.20 years (

Stevia diversipapposa was first described by Hieronymus in 1897, along with its forms breviaristata, exaristata and longiaristata. All these names are considered as later synonyms of S. vaga, a widespread shrub from northwestern and central Argentina, described by Grisebach in 1874. During our revision of the Argentinian species of Stevia, we found that type designations were missing for S. diversipapposa and its forms breviaristata and exaristata. Three specimens of CORD herbarium are chosen here as the lectotype of S. diversipapposa, and the neotypes of S. diversipapposa f. breviaristata and S. diversipapposa f. exaristata. Additionally, we provide a re-description of the species and a distribution map of S. vaga.

Although children and adolescents with acute lymphoblastic leukaemia (ALL) have high survival rates, approximately 15-20% of patients relapse. Risk of relapse is routinely estimated at diagnosis by biological factors, including flow cytometry data. This high-dimensional data is typically manually assessed by projecting it onto a subset of biomarkers. Cell density and “empty spaces” in 2D projections of the data, i.e. regions devoid of cells, are then used for qualitative assessment. Here, we use topological data analysis (TDA), which quantifies shapes, including empty spaces, in data, to analyse pre-treatment ALL datasets with known patient outcomes. We combine these fully unsupervised analyses with Machine Learning (ML) to identify significant shape characteristics and demonstrate that they accurately predict risk of relapse, particularly for patients previously classified as ‘low risk’. We independently confirm the predictive power of CD10, CD20, CD38, and CD45 as biomarkers for ALL diagnosis. Based on our analyses, we propose three increasingly detailed prognostic pipelines for analysing flow cytometry data from ALL patients depending on technical and technological availability: 1. Visual inspection of specific biological features in biparametric projections of the data; 2. Computation of quantitative topological descriptors of such projections; 3. A combined analysis, using TDA and ML, in the four-parameter space defined by CD10, CD20, CD38 and CD45. Our analyses readily extend to other haematological malignancies.Author summaryAcute lymphoblastic leukaemia (ALL) is a blood cancer which affects predominantly children and adolescents. Therapy typically fails in approximately 20 % of patients, who suffer from relapse. To determine disease status, clinicians assess cell types, their interactions, as well as deviations from normal behaviour. Flow cytometry (FC) is a method that quantifies the intensity of specific cell markers, giving rise to high-dimensional data. This routinely collected information is then reduced to obtain human-interpretable visualisation for prognosis. Topological Data Analysis (TDA) is a field of mathematics that studies shapes in data, considering isolated data islands and empty spaces between them. We showcase how to use TDA to extract shape characteristics in FC data of relapsing patients. We propose three pipelines, of increasing methodological complexity, to aid clinical decisions for risk stratification in ALL. In combination with Machine Learning, TDA enables high-accuracy predictions of relapse to be made at the time of diagnosis.

This study examined a moderated mediation model testing whether dysmorphic concern is related to behaviour altered to change appearance. This relationship is potentially mediated by depressive symptomatology (dysphoria and self-esteem) and ideas of reference about "laughing, commenting" and "attention, appearance," and each mediated relationship moderated by sex. The sample was made up of 3377 adolescents from 12 to 18 years old (Mage = 14.52; SD = 1.65, 56.5% girls). The results showed that dysphoria and ideas of reference about "laughing, commenting" and "attention, appearance" partially mediated the relationship between dysmorphic concern and behavioural impairment related to body image. The relationship with dysphoria was moderated by sex, such that the mediation effect was stronger in girls than in boys. This result implies that girls who are worried about some characteristic of their appearance and show dysphoria are at greater risk of altered behaviour involving avoidance or controlling their appearance than boys. In addition, a possible risk of body dysmorphic disorder (3.45% of the sample) was found, with very prominent hiding behaviour using clothing or control behaviours, such as frequent weighing and looking at oneself in the mirror too much. Implications of these findings are discussed.

[Objective] The purpose of this article was to study the relationship of self‐focused attention and dissociation with the dialogical relationship persons diagnosed with psychosis have with their voices., [Method] The DAIMON Scale was applied to 62 persons diagnosed with psychosis to measure the dialogical relationship with their voices, and the Cambridge depersonalization scale, the Tellegen absorption scale, and the self‐focused attention scale., [Results] The results showed that the dialogical relationship with the voices was associated with high levels of self‐focused attention (private and public), depersonalization, and absorption. It was also found that absorption mediated significantly between public self‐focused attention and the dialogical relationship with the voices., [Conclusions] The role of dissociation and self‐focused attention in forming the dialogical relationship a person with psychosis has with the voices is discussed and approaches to treatment are suggested.

The synthesis of rigid polyurethane (RPU) foams containing thermoregulatory microcapsules has been carried out under reduced pressure conditions with a new foaming formulation to reduce the final composite densities. These optimized RPU foams were able to overpass the drawbacks exhibited by the previous composites over the studied temperature range, working as insulating and thermal energy storage materials. The change in the formulation allowed to decrease the final foam density and enhance their mechanical strength. The effect of the operating pressure (atmospheric, 800 mbar, and 700 mbar) and microcapsules content (up to 30 wt%) on the physical, mechanical, and thermal PU foam properties was studied. The reduction of the pressure from atmospheric to 800 mbar did not have any effect on the cell size, strut thickness, and compression strength 10% of deformation, the Young modulus being even higher at 800 mbar. Nevertheless, a strong impact on the microstructure and mechanical properties was observed for the foam composites obtained at 700 mbar. A deleterious impact on the RPU foams thermal conductivity was observed when using low-pressure conditions. Thermal analyses showed that a composite able to work as heat accumulator and thermal insulation both at transient and at steady state was achieved.

The innate immune system uses inflammasomal proteins to recognize danger signals and fight invading pathogens. NLRP3, a multidomain protein belonging to the family of STAND ATPases, is characterized by its central nucleotide-binding NACHT domain. The incorporation of ATP is thought to correlate with large conformational changes in NLRP3, leading to an active state of the sensory protein. Here we analyze the intrinsic ATP hydrolysis activity of recombinant NLRP3 by reverse phase HPLC. Wild-type NLRP3 appears in two different conformational states that exhibit an approximately fourteen-fold different hydrolysis activity in accordance with an inactive, autoinhibited state and an open, active state. The impact of canonical residues in the nucleotide binding site as the Walker A and B motifs and sensor 1 and 2 is analyzed by site directed mutagenesis. Cellular experiments show that reduced NLRP3 hydrolysis activity correlates with higher ASC specking after inflammation stimulation. Addition of the kinase NEK7 does not change the hydrolysis activity of NLRP3. Our data provide a comprehensive view on the function of conserved residues in the nucleotide-binding site of NLRP3 and the correlation of ATP hydrolysis with inflammasome activity.

In this paper a 3D numerical model using a software based on the Finite Element Method (FEM), was developed and validated using the results obtained in a geotechnical centrifuge model of a piled raft system founded in soft soils undergoing regional subsidence. The piled raft configuration had nine piles distributed in the center of the raft. The kaolin parameters were obtained, calibrated, and validated for the Hardening Soil Model (HSM), based on laboratory triaxial and oedometer test results. Also, a single pile load test was carried out in the centrifuge to get the resistance parameters used in the FEM. The developed numerical model reproduced satisfactorily soil and foundation consolidation displacements due, not only by the structural service load but also by the pore pressure drawdown. For load distribution on piles and raft, the model reproduces with good agreement the foundation behavior only for the structural service load, for pore pressure drawdown some adjustments on the embedded piles elements shaft and base resistance had to be done. The developed model allowed to identify the most sensitive parameters for this type of simulation, to define the types and stages of analysis that had the best fit for the physical model, and to obtain additional results to those measured in the physical model, e.g., the axial load distribution developed along the piles and therefore the magnitude of the negative skin friction, that is an important load that should be considered for the structural safety review of piled foundations subjected to this complex conditions.

Background: BO-112 is a double stranded synthetic RNA formulated with polyethyleneimine that mimics a viral infection. Through dendritic cells activation, increase in CD8 T-cell infiltration and interferons induction, it produces an immunogenic cell death. Phase 1 study (NCT02828098) showed ORR 20% in patients (pts) with anti PD-1 resistant melanoma (mel). Hence phase 2 trial was designed. Study design: Single arm study (NCT04570332) with intratumoral BO-112 plus intravenous pembrolizumab in pts with mel (cutaneous, acral or mucosal) and confirmed progressive disease (PD) while on anti-PD1 based therapy. Pts were treated with BO-112, 1-2 mg on a weekly basis for 7 weeks and thereafter Q3W in 1-8 different lesions. Pembrolizumab 200 mg was administered Q3W. Primary endpoint was overall response rate (ORR) by RECIST 1.1 by independent reviewer. Secondary endpoints included disease control rate (DCR), progression free survival (PFS) and safety. Exploratory objectives included radiomic signatures, itRECIST and evaluation of tumor microenvironment. At least 20% of pts had to achieve response in order to consider primary endpoint met. Results: Recruitment was completed 24th August 2021 with 42 pts; female 43%; median age 66 (rank 27-88). Table summarizes basal characteristics. With 40 evaluable for response pts, 10 achieved response (25%): 3 complete response (CR) and 7 partial response (PR). 17 pts (44%) achieved a stable disease (SD), meaning a DCR of 68% with 18 pts still on treatment. The 4 pts with a baseline LDH>3xULN developed PD no later than week 8. Responses per histology were: 66% mucosal, 28% cutaneous, 0% acral. Responses per BRAF/NRAS status were: BRAF mutant (Mut) 43%, NRAS Mut 31%, and BRAF/NRAS wild type (WT) 17%. 33 pts (79%) had at least one BO-112 related adverse event (AE) being only in 2 cases grade>3 (G4 infusion reaction and G3 myalgia). Most common related AEs were asthenia, pyrexia, diarrhea, vomiting and chills. Study treatment was not discontinued in any pts due to related AE. Conclusions: The primary efficacy endpoint has been met. Additionally, disease control (PR+CR+SD) is meaningful and durable in a population with no current standard treatment options. Very high LDH levels (LDH >3xULN) and acral mel could predict poor outcome. Safety profile was manageable without treatment discontinuation due to AEs. N (ITT pts, 42) (%) AJCC8 M1C/D 19 (45) BRAF Mut 7 (17) WT 35 (83) Previous treatment Ipilimumab-nivolumab 6 (15) Anti PD-1 monotherapy 33 (79) Other combo 3 (7) Prior line indication Adjuvant 11 (26) Advanced 31 (74) LDH >ULN 17 (41) Best ORR (IRCR evaluable pts, N=40) Global Mucosal Cutaneous Acral ORR 10 (25) 2 (66) 8 (28) 0 PR 7 (18) 1 (33) 6 (21) 0 CR 3 (8) 1 (33) 2* (7) 0 SD 17 (43) 1 (33) 13 (45) 3 (37) PD 13 (33) 0 8 (28) 5 (63) *2 pts had pathologic CR and RECIST SD Citation Format: Iván Márquez-Rodas, Caroline Dutriaux, Philippe Saiag, Luis de la Cruz Merino, Eduardo Castanon Álvarez, Caroline Robert, Juan F. Rodríguez-Moreno, Ana M. Arance, Pablo Cerezuela-Fuentes, Henry Montaudié, Miguel F. Sanmamed, María González Cao, Julie Charles, María Pilar López Criado, Alfonso Berrocal, Enrique de Miguel, Elisa Funk-Brentano, Sorilla Prey, María del Carmen Álamo de la Gala, Javier Sánchez López, Helena Escuin-Ordinas, Sonia Macia, Marisol Quintero, Marya F. Chaney, Stéphane Dalle. Efficacy of intratumoral BO-112 with systemic pembrolizumab in patients with advanced melanoma refractory to anti-PD-1-based therapy: Final results of SPOTLIGHT203 phase 2 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT014.

Background: There is a lack of predictive biomarkers for immunotherapy in melanoma. Immunohistochemistry and gene sequencing are frequently assessed as part of clinical research. Radiomic signatures may also add valuable information, based on parameters which can be related to immune infiltration, therefore defining an imaging biomarkers panel for this clinical scenario. BO-112 is a double stranded synthetic RNA formulated with polyethyleneimine (PEI) that, by mimicking the effect of a viral infection, mobilizes the immune system. The role of imaging biomarkers is being explored in the present phase II clinical trial. Study design: Single arm study with BO-112 plus pembrolizumab (NCT04570332) in patients with advanced melanoma in progression to anti-PD1 therapy. As part of exploratory objectives, a radiomics analysis was performed to detect changes in lesion texture features. Quantitative features were obtained by using Quibim Precision 2.9 platform (Quibim, Valencia, Spain) after the manual delineation of lesions on the CT study of each subject at each timepoint to obtain information about injected/non-injected lesions. Images were normalized by taking into account Hounsfield Units (HU) bias across scanners in a cross-calibration phantom and the Z-score. The difference (Delta) in the features between baseline and week 8 was calculated. Results: Studies were assessed based on event (progression) and based on whether lesions had been injected. Patients with only cutaneous disease were not included in this analysis. Out of 23 patients who had at least two imaging assessments, 6 developed progressive disease by week 8, and 17 subjects had no event by that time. Due to the small sample size, the radiomic analysis was based on hypothesis testing. With regards to volume, 50% of the non-progressing lesions reduced their value from that of the baseline. Regarding injected versus non-injected changes, up to 50% of injected lesions decreased their volume after 8 weeks of injected treatment whereas in non-injected lesions volume decreased in less than 25% of lesions. From the independent sample t-test of delta radiomics features against the injected/non-injected lesions variable, there were 4 features with a statistically significant difference between groups; all of them related to the Low Grey-Level Zone Emphasis. Specifically, Delta original GLRLM Low Grey-Level Run Emphasis showed the highest significant difference between injected and non-injected lesions (p=0.004), with higher and positive delta values in the injected group (75% injected lesions were above 0). Conclusions: Imaging biomarkers provide a large number of quantitative image features with a wide span of information, from size to heterogeneity of the tissue which may be indicator of tumor progression and immune infiltrate. In the analysis of radiomics features, delta GLRLM low grey-level zone emphasis was sensitive to the tumoral changes happening in injected lesions at week 8. This might add insights into the imaging-based evaluation of immune infiltration in intratumoral immunotherapy and the creation of associated imaging biomarkers panels. Citation Format: Paula Moreno, Philippe Saiag, Luis de la Cruz Merino, Caroline Dutriaux, Eduardo Castanon Álvarez, Caroline Robert, Juan F. Rodríguez-Moreno, Pablo Cerezuela-Fuentes, Ana M. Arance, Henry Montaudié, Miguel F. Sanmamed, María González Cao, María Pilar López Criado, Julie Charles, Alfonso Berrocal, Enrique de Miguel, Elisa Funk-Brentano, Pablo Sau Llanas, Sorilla Prey, Eva Muñoz-Couselo, Delvys Rodríguez Abreu, Juan Martin-Liberal, Ángel Alberich-Bayarri, Javier Sánchez López, Sonia Macia, Marisol Quintero, Marya F. Chaney, Stéphane Dalle, Iván Márquez-Rodas. Radiomic features in tumor assessment, preliminary results from a phase 2 study of intratumoral administration of BO-112 with pembrolizumab in patients with anti PD1 refractory melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT109.

Background: There is a lack of predictive biomarkers for immunotherapy in melanoma. In terms of IHC, there is no strong rational to support the use of PD-L1 expression. BRAF mutations occur in 40-50% of melanomas and the MAPK pathway may also be activated by NRAS mutations. Patients harboring these mutations face usually a worse prognosis. BO-112 is a double stranded synthetic RNA formulated with polyethyleneimine (PEI) that, by mimicking the effect of a viral infection, mobilizes the immune system. Prior data from a phase I trial (NCT02828098) suggest that, when administered intratumorally, it causes an increase in CD8 infiltration and PD-L1 expression. The role of these and other biomarkers is being explored in the present phase II clinical trial. Study Design: Single arm study with BO-112 plus pembrolizumab (NCT04570332) in patients with advanced melanoma in progression to anti-PD1 therapy. Tumors were genotyped by next generation sequencing, whole exome sequencing and tumor mutation burden. Antitumor and immunological effects of the treatment in the tumor microenvironment were assessed by PDL1 and CD8 immunohistochemistry with a paired biopsy performed after 21 days of treatment. Results: A preliminary analysis has been performed, based on patients evaluable for clinical benefit (defined as response or stable disease>16 weeks). Samples from 35 patients have been analyzed, with 24 patients paired biopsies available. Patients with “cold” tumors (PD-L1 negative and CD8 low) at baseline had a trend to lack of clinical benefit. Only basal PD-L1 in the inflammatory component showed a statistically significant correlation with clinical outcome (4/20 (25%) tumors PDL1 IC negative had benefit versus 10/15 (67%) positive), p=0.0053. Fifteen patients had an increase in PD-L1 and 14 patients had increase in CD8 infiltrate after BO-112 treatment; the lack of increase in PDL1 and CD8 after treatment was also predictive of lack of response (p=0.04). BRAF/NRAS driver mutations correlated with positive outcome. Clinical benefit was observed in 4 of 17 (24%) patients not carrying activating mutations whereas 11 out of 18 (61%) patients with BRAF/NRAS activating mutations had clinical benefit (p=0.02), mainly in cutaneous histology (14% versus 65%, p=0.02). Mucosal melanoma patients (n=3) achieved an ORR 66.7% and DCR 100%. The two mucosal melanoma patients with partial response harbored SETD2 mutations and one of them showed extensive cyclic nucleotide-gated (CNGs), indicative of defects in DNA repair pathways. Regarding acral melanoma patients (n=9), no responses were observed, even in the single case with a NRAS mutation. The only patient achieving clinical benefit, with stable disease>16 weeks; had a unique mutation profile, with TP53 (inactivating) and KIT (activating) mutations. Conclusions: Patients basal mutant BRAF/NRAS could have more probability of benefit from BO-112 and pembrolizumab combination. PD-L1 and/or CD8 increase is an early marker of response. These findings could help to select patients in future clinical trials. Further investigation into predictive biomarkers is warranted. Citation Format: Ruth Roman, Philippe Saiag, Caroline Dutriaux, Luis de la Cruz Merino, Eduardo Castanon, Miguel F. Sanmamed, Caroline Robert, Juan F. Rodríguez-Moreno, Pablo Cerezuela-Fuentes, Ana M. Arance, María González Cao, Henry Montaudié, María Pilar López Criado, Julie Charles, Alfonso Berrocal, María del Carmen Álamo de la Gala, Enrique de Miguel, Elisa Funk-Brentano, Sorilla Prey, Eva Muñoz-Couselo, Delvys Rodríguez Abreu, Juan Martín-Liberal, Helena Escuin-Ordinas, Mark Branum, Sonia Macia, Marisol Quintero, Javier Sánchez López, Marya F. Chaney, Beatriz García-Peláez, Marta Vives-Usano, Miguel Ángel Molina, Stéphane Dalle, Iván Márquez-Rodas. Correlation of biomarkers and clinical benefit of intratumoral BO112 and pembrolizumab in patients with anti PD1 refractory melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT107.

Evidence-Based Psychological Treatments for Adults: A Selective Review.Psychological treatments have shown their efficacy, effectiveness, and efficiency in dealing with mental disorders. However, considering the scientific knowledge generated in recent years, in the Spanish context, there are no updating studies about empirically supported psychological treatments. The main goal was to carry out a selective review of the main empirically supported psychological treatments for mental disorders in adults.Levels of evidence and degrees of recommendation were collected based on the criteria proposed by the Spanish National Health System (Clinical Practice Guidelines) for different psychological disorders.The results indicate that psychological treatments have empirical support for the approach to a wide range of psychological disorders. These levels of empirical evidence gathered range from low to high depending on the psychological disorder analysed. The review indicates the existence of certain fields of intervention that need further investigation.Based on this selective review, psychology professionals will be able to have rigorous, up-to-date information that allows them to make informed decisions when implementing empirically based psychotherapeutic procedures based on the characteristics of the people who require help.

Copolymers from ethylene oxide (EO) and propylene oxide (PO) functionalized with glycidyl propargyl ether (GPE) are synthesized. The GPE allows further attachment of drugs but its influence on the polymeric micelle formation is unknown. In this work, the influence of the structure of these copolymers on their critical micellar concentration (CMC) in water and in the size and stability of obtained micelles is studied. For this purpose, the presence of GPE, the copolymer type (gradient or block), the EO:PO ratio and the initiator (water or ethanol) are modified. Gradient copolymers can be synthesized in a single step thanks to the different monomers reactivity, simplifying the process and obtaining similar CMC values to the block copolymers. The use of ethanol as initiator decreases the block copolymer CMC and increases the polydispersity. Besides, the presence of the GPE does not impede the micelle formation and has low effect on the copolymer CMCs. Finally, the higher the EO:PO ratio, the higher the CMC and the smaller the size of micelles. Moreover, Z-potential, DLS and HRSEM analyses show that the micelles are stable, spherical, capable to incorporate coumarin (a hydrophobic drug) and with apparent hydrodynamic sizes suitable to be absorbed by target cells., Se sintetizan copolímeros de óxido de etileno (EO) y óxido de propileno (PO) funcionalizados con glicidil propargil éter (GPE). El GPE permite una mayor unión de fármacos pero se desconoce su influencia en la formación de micelas poliméricas. En este trabajo se estudia la influencia de la estructura de estos copolímeros en su concentración micelar crítica (CMC) en agua y en el tamaño y estabilidad de las micelas obtenidas. Para ello se modifica la presencia de GPE, el tipo de copolímero (gradiente o bloque), la relación EO:PO y el iniciador (agua o etanol). Los copolímeros de gradiente se pueden sintetizar en un solo paso gracias a la reactividad de los diferentes monómeros, simplificando el proceso y obteniendo valores de CMC similares a los copolímeros de bloque. El uso de etanol como iniciador disminuye la CMC del copolímero en bloque y aumenta la polidispersidad. Además, la presencia del GPE no impide la formación de micelas y tiene un efecto bajo sobre las CMC del copolímero. Finalmente, cuanto mayor sea la relación EO:PO, mayor será la CMC y menor el tamaño de las micelas. Además,Los análisis de potencial Z , DLS y HRSEM muestran que las micelas son estables, esféricas, capaces de incorporar cumarina (un fármaco hidrofóbico) y con tamaños hidrodinámicos aparentes adecuados para ser absorbidos por las células diana.

Three different approaches to estimate the vapor pressure by thermogravimetric analyses (TGA) of commercial paraffins-based phase change materials (PCMs) have been compared. The known Langmuir vaporization relation and two additional models based on the mass transfer by molecular diffusion at isothermal and non-isothermal conditions, using the Fuller equation for estimating binary diffusion coefficients in the gas phase, were developed. The Antoine equation was used to express vapor pressure as function of temperature and the unknown constants were obtained by non-linear regression. n-Hexadecane and n-decane were used as reference compounds to estimate the deviation between experimental and predicted values. The non-isothermal model exhibited the highest accuracy for obtaining the vapor pressure and allowed to obtain boiling points and heat of vaporizations very close to those reported for the reference compounds.

ResumenRecientemente, las investigaciones centradas en estudio de las bases de la psicosis han puesto el acento en la saliencia aberrante (Kapur, 2003). Asimismo, se ha demostrado que los sistemas emocionales propuestos por Gray (1982), relacionados con la sensibilidad al castigo y la sensibilidad a la recompensa, influyen en el desarrollo de diversas psicopatologías. Apenas se ha investigado sobre el papel de estos sistemas en la sintomatología positiva. El objetivo de este trabajo fue estudiar el papel mediador de la sensibilidad al castigo y la sensibilidad a la recompensa en la relación entre la saliencia aberrante y la sintomatología positiva, entendida como ideas de referencia, ideas persecutorias y propensión alucinatoria en una muestra compuesta por 259 estudiantes de la Universidad de Sevilla (España). Los resultados mostraron una mediación parcial de la sensibilidad al castigo y la sensibilidad a la recompensa en el modelo de mediación de las ideas de referencia, así como una mediación parcial de la sensibilidad a la recompensa en el modelo de la propensión alucinatoria. No obstante, no se observó mediación ni de la sensibilidad al castigo ni de la sensibilidad a la recompensa en el modelo de las ideas persecutorias. Según estos resultados, parecer ser que la sensibilidad al castigo y la sensibilidad a la recompensa son características básicas de la personalidad que podrían influir en el desarrollo de algunos síntomas positivos, y por ello, de la psicosis.AbstractRecently, research focused on the study of the bases of psychosis has placed the accent on aberrant salience (Kapur, 2003). Likewise, it has been shown that the emotional systems proposed by Gray (1982), related to sensitivity to punishment and sensitivity to reward, influence the development of various psychopathologies. The role of these systems in psychosis has hardly been investigated. The objective of this work was to study the mediating role of sensitivity to punishment and sensitivity to reward in the relationship between aberrant salience and positive symptomatology, understood as ideas of reference, persecutory ideas and hallucinatory propensity in a sample composed of 259 students of the University of Seville (Spain). The results showed a partial mediation of the sensitivity to punishment and the sensitivity to reward in the mediation model of the ideas of reference, as well as a partial mediation of the SR in the model of the hallucinatory propensity. However, no mediation was observed neither of the sensitivity to punishment nor of the sensitivity to reward in the persecutory ideas model. According to these results, it seems that the sensitivity to punishment and sensitivity to reward are basic characteristics of the personality that could influence the development of some positive symptoms, and therefore, of psychosis.

ResumenEn la investigación clínica, el afecto positivo ha recibido menos atención que su dimensión paralela: el afecto nega­tivo. Este trabajo analiza las propiedades psicométricas de la Escala de Afectividad Positiva (Response to Positive Affect), para su adaptación al castellano y validación en población española. La escala mide las respuestas a las emociones experimentadas ante situaciones positivas (regulación emocional). Según los autores de la escala, está compuesta por tres factores: Amortiguación, Rumia positiva centrada en la emoción y Rumia positiva centrada en la persona. Se llevaron a cabo análisis factoriales exploratorio y confirmatorio, con 970 participantes de población general y clínica, análisis de la consistencia interna, invarianza para sexo y grupo (pa­cientes/controles) y validez concurrente. Se obtuvo la misma estructura factorial planteada por los creadores de la versión original de la escala. Se obtuvieron adecuados valores para la consistencia interna, invarianza para sexo y pacientes/controles, y correlaciones significativas con el cuestionario de salud general y el Cuestionario de Sensibilidad al Castigo y Sensibilidad a la Recompensa de sensibilidad al castigo y a la recompensa. La escala presenta adecuadas propiedades psicométricas. La Escala de Afectividad Positiva es un instrumento que puede permitir el estu­dio y análisis de la rumia positiva y la amortiguación, por tanto, la regulación de los estados emocionales positivos, complementando otros instrumentos centrados en otros procesos como la rumia y la afectividad negativa. Puede ser particularmente útil para la evaluación, seguimiento, y planificación de la intervención ante trastornos de ansie­dad, depresivos y bipolares, entre otros, al evaluar carac­terísticas de regulación emocional en la persona evaluada.AbstractPossitive affect has often been neglected throughout research in clinical psychology, with respect to its parallel dimension: Negative affect. This study analyses the psychometric properties of the Response to Positive Affect scale in order for it to be adapted and validated in Spanish population. The scale measures people reaction to the emotions experienced from positive situations (emotion regulation). According to the authors of the scale, it is compossed by three factors: Dampening, Emotion-focused possitive rumination and Self-focused possitive rumination. An exploratory and confirmatory factor analysis were carried out, with 970 participants from general and clinical population, along with analyses about internal consistency, invariance analysis for gender and group (patients/controls) and concurrent validity. The factors obtained were the same as the ones proposed by the creators of the original scale. Furthermore, the values for internal consistency were adecuate, invariance for sex and group (patients/controls), as well as the correlations with the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (sensitivity to punishment and reward). The scale has good psychometric properties. The Response to Positive Affect scale is an instrument that can allow the study and analysis of positive rumination and damping, therefore, the regulation of positive emotional states, complementing other instruments focused on processes as rumination or negative affectivity. It can be particularly useful for the evaluation, follow-up, and planning of the intervention in anxiety, depressive, and bipolar disorders, among others, when analyzing characteristics of emotional regulation.

Hydrophobic release agents were developed from SiO2-CH3 submicron-sized particles containing hydrophilic and hydrophobic functional groups dispersed into a vegetable oil as support. The SiO2-CH3 submicron-sized particles were synthesized by changing the molar ratio between the precursors Tetraethyl orthosilicate (TEOS) and Methyltriethoxysilane (MTES) from 0.66 to 5 (MTEOS-0.66 to MTEOS-5), being the relative amount of SiO2-CH3 quantified by FTIR technique. Mortar specimens having hydrophobic properties were manufactured using 3 wt% of the above SiO2-CH3 submicron-sized particles. Additionally, the concentration effect was studied by using MTEOS-0.66 within 3–10 wt%. The hydrophobic properties of the mortar specimens were checked by measuring the contact angle within water droplets and surface. The particle size increased with the MTES/TEOS molar ratio and according to the hydrophobic properties, the proper release agent must be synthesized by using MTEOS-2.5 dispersed into the vegetable oil and having a concentration of 3 wt%. This hydrophobic release agent led mortar surfaces with contact angles higher than 145°. Waterproofing and mechanical studies on concrete specimens allowed to conclude that this demoulding agent does not have a high penetration depth but improved the concrete waterproofing properties, without depletion in the compressive strength.

An in situ shape-stabilized phase change material (ssPCM) from polyethylene glycol (PEG) has been produced by sol–gel method. The inorganic matrix was in situ formed from tetraethyl orthosilicate (TEOS), controlling the condensation rate in a second alkaline step using NaOH. ssPCMs having a latent heat up to 113.8 J/g were synthetized using a sol with a molar ratio H2O:EtOH:H2SO4:PEG1000:TEOS of 2:0.34:0.021:0.50:1 and an equivalent ratio NaOH/H2SO4 of 1.15 for promoting the gel step. The presence of high-density hydrogen bonds between silanol groups and the ether oxygen atoms of PEG and the existence of latent heat allowed to confirm that the PEG worked in two ways. It either forms the PEG–SiO2 matrix or adsorbs onto the surface of the previous polymeric matrix, losing or conserving its latent heat, respectively. The addition of NaOH allowed to change the functionality of the silicon matrix which strongly affected the water content, the thermal stability, and the amount of active PEG in the ssPCMs, leading to an optimal neutralization condition when an equivalent ratio NaOH/H2SO4 of 1.15 was used. The obtained ssPCM has an appropriate range of operative temperatures, a high latent heat in the range of common thermoregulating materials, and a proper thermal reliability.

Rigid PU foams are properly recycled by a single-phase glycolysis process employing crude glycerol as transesterification agent. A high pure recovered polyol (71% of purity) was obtained using a mass ratio of PU scraps to crude glycerol of 1 to 1, a reaction temperature of 190 °C and stannous octoate as catalyst in a 1.3 wt% concentration. PU foam composites containing thermoregulating microcapsules constituted by a paraffin core (Rubitherm®RT27) and a polymer shell material (LDPE and EVA) were glycolyzed, allowing to recover the microcapsules components and the polyol separately. This way, both components of the composite are recovered and can be reused in the manufacturing of new products; demonstrating for first time the viability of the chemical recycling of this kind of composites. Besides, the developed process was successfully applied for foams containing different proportions between the hard and soft segments, demonstrating its robustness. Finally, the recovered polyols were successfully employed to replace a raw rigid polyether polyol in the synthesis of new rigid PU foams. The most important physical and mechanical properties (density, maximum compressive strength and Young modulus) were maintained constant for the incorporation up to a 25 wt% of recovered polyol coming from conventional rigid PU foam scraps and up to a 37.5 wt% with the recovered polyol from rigid PU foam containing thermoregulating microcapsules. Regarding the effective thermal conductivity, it remained constant, even with 100 wt% of recovered polyol from PU scraps with thermoregulating microcapsules., Las espumas rígidas de PU se reciclan adecuadamente mediante un proceso de glucólisis de una sola fase que emplea glicerol crudo como agente de transesterificación. Se obtuvo un poliol recuperado de alta pureza (71 % de pureza) usando una relación de masa de desechos de PU a glicerol crudo de 1 a 1, una temperatura de reacción de 190 °C y octoato estannoso como catalizador en una concentración de 1,3 % en peso. Compuestos de espuma de PU que contenían microcápsulas termorreguladoras constituidas por un núcleo de parafina (Rubitherm®RT27) y un material de cubierta de polímero (LDPE y EVA) fueron glicolizados, lo que permitió recuperar los componentes de las microcápsulas y el poliol por separado. De esta forma, ambos componentes del composite se recuperan y pueden reutilizarse en la fabricación de nuevos productos; demostrando por primera vez la viabilidad del reciclaje químico de este tipo de composites. Además, el proceso desarrollado se aplicó con éxito para espumas que contenían diferentes proporciones entre los segmentos duros y blandos, demostrando su robustez. Finalmente, los polioles recuperados se emplearon con éxito para reemplazar un poliol de poliéter rígido crudo en la síntesis de nuevas espumas rígidas de PU. Las propiedades físicas y mecánicas más importantes (densidad, resistencia máxima a la compresión y módulo de Young) se mantuvieron constantes para la incorporación de hasta un 25 % en peso de poliol recuperado procedente de desechos de espuma de PU rígida convencional y hasta un 37,5 % en peso con el poliol recuperado. de espuma rígida de PU que contiene microcápsulas termorreguladoras. En cuanto a la conductividad térmica efectiva, se mantuvo constante, incluso con 100% en peso de poliol recuperado de desechos de PU con microcápsulas termorreguladoras.

The morphology and encapsulation efficiency of thermoregulating microcapsules based on a spreading coefficient theory and polar surface energy component were evaluated. For this purpose the microencapsulation of phase change materials (PCMs) with different copolymer shells and using different suspending agents by the suspension-like polymerization technique has been carried out. Contact angles and interfacial tensions were measured, and results were discussed with respect to the internal structure as well as encapsulation efficiency of the microcapsules. A core/shell structure was expected as the equilibrium morphology, whereas the experimental structure exhibited a matrix morphology. A core-shell structure was favored by increasing the polarity of the polymer and decreasing the solubility between the core and shell. The type and amount of suspending agent do not have a significant influence on the final characteristic of the microcapsules. Shells with various polarities were synthesized from styrene (S), divinylbenzene (DVB) and hexa(methacryloylethylenedioxy)cyclotriphosphazene (PNC-HEMA), and it was found that a core-shell structure was only obtained for microcapsules with a high polar surface energy component.

Empirical evidence suggests that schizotypy is a useful construct for analyzing and understanding psychotic disorders. However, several issues remain to be resolved.This selective, critical review, addresses some questions and limitations, and discusses future directions of work.First, we present a conceptual outline and discuss the evidence from translational and interdisciplinary studies on schizotypy. Next, we examine and discuss newer analytical and methodological approaches, including network and machine learning approaches. We also discuss newer psychometric identification approaches, such as those using biobehavioral and ambulatory assessment. Next, we review recent cross-cultural studies in schizotypy research. Finally, we identify new challenges and directions and draw conclusions.This selective, critical review suggests that new methods can contribute to the construction of a solid scientific model of schizotypy as a risk construct.

A novel form-stable phase-change material (PCM) based on facing bricks was developed by incorporating thermoregulating PEG-SiO2, synthetized by sol-gel method and based on polyethylene glycol as phase-change material and silica as stabilizer compound. The PEG-SiO2 in its liquid form (sol) is firstly adsorbed inside the porous brick and lastly stabilized (gel) by controlling its gelation time, obtaining form-stable PCMs with PEG-SiO2 contents within 15–110 wt.%. Kinetic adsorption curves of the sol into bricks having different porosities as well as maximum adsorption capacities were obtained. The effective diffusion coefficients (Deff) were estimated by means of Fick’s second law, it being possible to predict the adsorption of sol PEG-SiO2 by the brick as function of its porosity and the free diffusion coefficient. Finally, form-stable PCMs demonstrated an improvement in their thermal energy storage capacity (up to 338%), these materials being capable of buffering the indoor temperature during an entire operational day

Introduction Dissociative symptoms are a type of phenomenon which is present in a wide variety of psychopathological disorders. It is therefore necessary to develop scales that measure this type of experience for therapy and research. Starting out from the bipartite model of dissociation, this study intended to adapt and validate the Detachment and Compartmentalization Inventory (DCI) in Spanish. Material and methods For this, 308 participants (268 from the community population and 40 with psychiatric pathology) completed the DCI, the Dissociative Experiences Scale (DES-II), the Somatoform Dissociation Questionnaire (SDQ20) and the Mindfulness Attention Awareness Scale (MAAS). Results The results showed that the Spanish version has a two-factor structure similar to the original version and was invariant across participants. The reliability of DCI scores was adequate and acquired evidence of validity related to other instruments. Conclusions It is concluded that the DCI is a valid scale for detecting detachment and compartmentalization dissociative experiences, both in the clinic and research.

Abstract Thermoregulating microcapsules (MC) with flame-retardant properties were used to produce polyurethane (PU) foams. Thermogravimetric analyses of the microcapsules performed under atmospheric air and nitrogen confirmed that the hexa(methacryloylethylenedioxy) cyclotriphosphazene (PNC-HEMA) monomer raised the amount of residue after exposure to high temperature, proving the formation of a thermally stable char layer. Additionally, the flame-retardant properties of the microcapsules were analyzed by micro-combustion calorimetry (MCC), and the PU foams were tested by both MCC and cone calorimetry. The total heat release and maximum heat release rate were lower for microcapsules containing the flame-retardant PNC-HEMA. The composition of the microcapsules has been proved by MCC and TGA, where the release of the encapsulated phase change material (PCM) occurred at the expected temperature. However, in PU foams, the release of PCM is shifted to higher temperatures. Accordingly, these materials can be considered as an important alternative to commonly used microcapsules containing phase PCMs, where a lower flammability is required for their future application. Graphic abstract

This article contains data related to the research article entitled "Carbon dioxide sorption and melting behavior of mPEG-alkyne". The presented data gives information on the thermodynamics properties of the solvent and the polymer. The time saturation of mPEG-alkyne in supercritical carbon dioxide (scCO2) was evaluated in a high-pressure variable volume cell in different period of time at different pressure at the same temperature. The effects of pressure and temperature on the density of CO2 when it is above supercritical conditions are determined with Sanchez Lacombe and Bender Equation and compared with the NIST database and values of equation of Bender. The characteristic parameters of CO2 were determined with the equations proposed by Chengyong Wang et al. [1] and the sum of squared error was calculated for each parameter. Furthermore in this work the solubility data of scCO2/polymer mixture were correlated with Sanchez Lacombe Equation of State (SL EOS) and Heuristic model proposed by Irene Pasquali et al. [2]. This work describes the methodology for solving the SL EOS between the polymer and scCO2 and the procedure of determining the solubility parameter with the group contribution method necessary to apply the heuristic model is described., Este artículo contiene datos relacionados con el artículo de investigación titulado "Sorción de dióxido de carbono y comportamiento de fusión de mPEG-alquino". Los datos presentados brindan información sobre las propiedades termodinámicas del solvente y el polímero. El tiempo de saturación de mPEG-alquino en dióxido de carbono supercrítico (scCO 2 ) se evaluó en una celda de volumen variable de alta presión en diferentes períodos de tiempo a diferentes presiones a la misma temperatura. Los efectos de la presión y la temperatura sobre la densidad del CO 2 cuando está por encima de las condiciones supercríticas se determinan con la ecuación de Sánchez Lacombe y Bender y se comparan con la base de datos del NIST y los valores de la ecuación de Bender. Los parámetros característicos del CO 2se determinaron con las ecuaciones propuestas por Chengyong Wang et al. [1] y se calculó la suma del error cuadrático para cada parámetro. Además, en este trabajo se correlacionaron los datos de solubilidad de la mezcla scCO 2 /polímero con la Ecuación de Estado de Sánchez Lacombe (SL EOS) y el modelo heurístico propuesto por Irene Pasquali et al. [2]. Este trabajo describe la metodología para resolver el SL EOS entre el polímero y el scCO 2 y se describe el procedimiento de determinación del parámetro de solubilidad con el método de contribución de grupo necesario para aplicar el modelo heurístico.

Empirically Supported Psychological Treatments for Children and Adolescents: State of the Art.The empirical evidence accumulated on the efficacy, effectiveness, and efficiency of psychotherapeutic treatments in children and adolescents calls for an update. The main goal of this paper objective was to carry out a selective review of empirically supported psychological treatments for a variety of common psychological disorders and problems in childhood and adolescence.A review was carried out of the psychological treatments for different psychological disorders and problems in social-emotional or behavioral adjustment in the child-adolescent population according to the Spanish National Health System (Clinical Practice Guidelines) levels of evidence and degrees of recommendation.The findings suggest that psychological treatments have empirical support for addressing a wide range of psychological problems in these developmental stages. The degree of empirical support ranges from low to high depending on the phenomenon analyzed. The review suggests unequal progress in the different fields of intervention.From this update, psychologists will be able to make informed decisions when implementing those empirically supported treatments to address the problems that occur in childhood and adolescence.

A new sustainable green protocol for obtaining polyethylene glycol (PEG) conjugates, with a prototype molecule, which in this work was coumarin, by means of click chemistry is presented. The organic solvents commonly used for this type of reaction were replaced by supercritical carbon dioxide (scCO2). The synthesis and characterization of PEG-coumarin were successfully reported using FTIR, 1H NMR, and MALDI TOF. Subsequently, a preliminary study was carried out using the response surface methodology to examine the variables that most affect the use of scCO2 as a reaction medium. The main effects caused by these variables, individually and their binary interaction, have been estimated. The response surface methodology has been used in this work to screen variables using a factorial design 23. The p-values of temperature and pressure were 0.006 and 0.0117, being therefore the most significant variables of the response surface methodology study. Subsequently, a more intensive study has been carried out on the variables that have shown the greatest significant effect on reaction performance where an 82.32% synthesis success was achieved, which broadens the scope of the use of scCO2 as a reaction medium. The conjugated coumarin with mPEG-alkyne and coumarin were evaluated for their in vitro antioxidant activities by the DPPH radical scavenging assay and were found to exhibit substantial activities. The click product showed comparable or even better efficacy than the initial coumarin., Se presenta un nuevo protocolo verde sostenible para la obtención de conjugados de polietilenglicol (PEG), con una molécula prototipo, que en este trabajo fue la cumarina, mediante química click. Los solventes orgánicos comúnmente utilizados para este tipo de reacción fueron reemplazados por dióxido de carbono supercrítico (scCO 2 ). La síntesis y caracterización de PEG-cumarina se informó con éxito utilizando FTIR, 1 H NMR y MALDI TOF. Posteriormente, se realizó un estudio preliminar utilizando la metodología de superficie de respuesta para examinar las variables que más inciden en el uso de scCO 2como medio de reacción. Se han estimado los principales efectos causados ​​por estas variables, individualmente y su interacción binaria. En este trabajo se ha utilizado la metodología de superficie de respuesta para cribar variables mediante un diseño factorial 2 3 . Los valores de p de temperatura y presión fueron 0,006 y 0,0117, siendo por tanto las variables más significativas de la metodología de superficie de respuesta estudiada. Posteriormente se ha realizado un estudio más intensivo sobre las variables que han mostrado un mayor efecto significativo en el rendimiento de la reacción donde se ha conseguido un 82,32% de éxito de síntesis, lo que amplía el alcance del uso de scCO 2como medio de reacción. La cumarina conjugada con mPEG-alquino y cumarina se evaluó en cuanto a sus actividades antioxidantes in vitro mediante el ensayo de captación de radicales DPPH y se encontró que exhibía actividades sustanciales. El producto clic mostró una eficacia comparable o incluso mejor que la cumarina inicial.