Short-term cultured tumor fragments to study immunotherapy combinations based on CD137 (4-1BB) agonism.

Biomarkers for cancer immunotherapy are an unmet medical need. The group of Daniela Thommen at the NKI recently reported on novel methodologies based on short-term cultures of patient-derived tumor fragments whose cytokine concentrations in the supernatants and activation markers on infiltrating T cells were associated with clinical response to PD-1 blockade. We set up a similar culture technology with tumor-derived fragments using mouse tumors transplanted into syngeneic immunocompetent mice to test an agonist anti-CD137 mAb and its combinations with anti-PD-1 and/or anti-TGF-ß. Increases in IFNγ concentrations in the tissue culture supernatants were detected upon in-culture activation with the anti-CD137 and anti-PD-1 mAb combinations or concanavalin A as a positive control. No other cytokine from a wide array was informative of stimulation with these mAbs. Interestingly, increases in Ki67 and other activation markers were substantiated in lymphocytes from cell suspensions gathered at the end of 72 h cultures. In mice bearing bilateral tumors in which one was excised prior to in vivo anti-CD137 + anti-PD-1 treatment to perform the fragment culture evaluation, no association was found between IFNγ production from the fragments and the in vivo therapeutic outcome in the non-resected contralateral tumors. The experimental system permitted freezing and thawing of the fragments with similar functional outcomes. Using a series of patient-derived tumor fragments from excised solid malignancies, we showed IFNγ production in a fraction of the studied cases, that was conserved in frozen/thawed fragments. The small tumor fragment culture technique seems suitable to preclinically explore immunotherapy combinations.

Extending the Scope of the C-Functionalization of Cyclam via Copper(I)-Catalyzed Alkyne-Azide Cycloaddition to Bifunctional Chelators of Interest.

Cyclam, known for its potent chelation properties, is explored for diverse applications through selective N-functionalization, offering versatile ligands for catalysis, medical research, and materials science. The challenges arising from N-alkylation, which could decrease the coordination properties, are addressed by introducing a robust C-functionalization method. The facile two-step synthesis proposed here involves the click chemistry-based C-functionalization of a hydroxyethyl cyclam derivative using Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC). Boc-protecting groups prevent undesired copper coordination, resulting in compounds with a wide range of functionalities. The optimized synthesis conditions enable C-functional cyclams to be obtained easily and advantageously, with high application potential in the previously cited fields. The methodology has been extended to trehalose-based Siamese twin amphiphiles, enabling efficient gene delivery applications.

Trehalose-polyamine/DNA nanocomplexes: impact of vector architecture on cell and organ transfection selectivity.

A novel family of precision-engineered gene vectors with well-defined structures built on trehalose and trehalose-based macrocycles (cyclotrehalans) comprising linear or cyclic polyamine heads have been synthesized through procedures that exploit click chemistry reactions. The strategy was conceived to enable systematic structural variations and, at the same time, ensuring that enantiomerically pure vectors are obtained. Notably, changes in the molecular architecture translated into topological differences at the nanoscale upon co-assembly with plasmid DNA, especially regarding the presence of regions with short- or long-range internal order as observed by TEM. In vitro and in vivo experiments further evidenced a significant impact on cell and organ transfection selectivity. Altogether, the results highlight the potential of trehalose-polyamine/pDNA nanocomplex monoformulations to achieve targeting transfection without the need for any additional cell- or organ-sorting component.

Vorticity phase separation and defect lattices in the isotropic phase of active liquid crystals.

We use numerical simulations and linear stability analysis to study the dynamics of an active liquid crystal film on a substrate in the regime where the passive system would be isotropic. Extensile activity builds up local orientational order and destabilizes the quiescent isotropic state above a critical activity, eventually resulting in spatiotemporal chaotic dynamics akin to the one observed ubiquitously in the nematic state. Here we show that tuning substrate friction yields a variety of emergent structures at intermediate activity, including lattices of flow vortices with associated regular arrangements of topological defects and a new state where flow vortices trap pairs of +1/2 defect that chase each other's tail. These chiral units spontaneously pick the sense of rotation and organize in a hexagonal lattice, surrounded by a diffuse flow of opposite rotation to maintain zero net vorticity. The length scale of these emergent structures is set by the screening length of the flow, controlled by the shear viscosity η and the substrate friction Γ, and can be captured by simple mode selection of the vortical flows. We demonstrate that the emergence of coherent structures can be interpreted as a phase separation of vorticity, where friction plays a role akin to that of birth/death processes in breaking conservation of the phase separating species and selecting a characteristic scale for the patterns. Our work shows that friction provides an experimentally accessible tuning parameter for designing controlled active flows.

Controlling liquid-liquid phase behaviour with an active fluid.

Demixing binary liquids is a ubiquitous transition explained using a well-established thermodynamic formalism that requires the equality of intensive thermodynamics parameters across phase boundaries. Demixing transitions also occur when binary fluid mixtures are driven away from equilibrium, but predicting and designing such out-of-equilibrium transitions remains a challenge. Here we study the liquid-liquid phase separation of attractive DNA nanostars driven away from equilibrium using a microtubule-based active fluid. We find that activity lowers the critical temperature and narrows the range of coexistence concentrations, but only in the presence of mechanical bonds between the liquid droplets and reconfiguring active fluid. Similar behaviours are observed in numerical simulations, suggesting that the activity suppression of the critical point is a generic feature of active liquid-liquid phase separation. Our work describes a versatile platform for building soft active materials with feedback control and providing an insight into self-organization in cell biology.

General infection prevention, mitigation, and control procedures implemented in the university education during the COVID-19 pandemic to achieve classroom attendance: a successful community case study.

Introduction: The COVID-19 pandemic entailed confinement and elimination of face-to-face university classes in Spain. The Francisco de Vitoria University in Madrid (UFV by its Spanish acronym) implemented risk management systems to enable on-campus university activity to avoid a negative impact on students, teachers, and faculties. Methods: A tracking/registry system was implemented to collect data, identify COVID-19-related cases, implement containment measures, and do follow-up in the UFV community (administration/services personnel [ASP], teaching/research personnel [TRP], and students), from September 2020 to April 2022. In addition, a prevention plan was implemented on campus to avoid COVID-19 spreading. Satisfaction with these measures was assessed through an online questionnaire. Results: A total of 7,165 suspected COVID-19 cases (84.7% students, 7.7% ASP, 6.5% TRP) were tracked (62.5% female cases, mean age (±SD) 24.8 years (±9.2 years)), and 45% of them confirmed (82% symptomatic/16% asymptomatic), being the student group that with the highest percentage (38.3% total tracked cases). The source of infection was identified in 50.6% of the confirmed cases (90.2% located off-campus). Nineteen COVID-19 outbreaks were registered (inside-10/outside-9). COVID-19 incidence rates were similar or lower than those reported in the Community of Madrid, except in the last wave, corresponding to Omicron variant. The degree of satisfaction (scale 1-6) with the implemented measures was high (scores 4.48-5.44). Conclusion: During the COVID-19 pandemic, UFV control measures, periodic monitoring, and the effectiveness of the tracking system have contributed to maintaining classroom teaching, guaranteeing health and safety. UFV has adapted to a new reality as an example of good practice for future pandemics or emergency situations.

Activity-Suppressed Phase Separation.

We use a continuum model to examine the effect of activity on a phase-separating mixture of an extensile active nematic and a passive fluid. We highlight the distinct role of (i) previously considered interfacial active stresses and (ii) bulk active stresses that couple to liquid crystalline degrees of freedom. Interfacial active stresses can arrest phase separation, as previously demonstrated. Bulk extensile active stresses can additionally strongly suppress phase separation by sustained self-stirring of the fluid, substantially reducing the size of the coexistence region in the temperature-concentration plane relative to that of the passive system. The phase-separated state is a dynamical emulsion of continuously splitting and merging droplets, as suggested by recent experiments. Using scaling analysis and simulations, we identify various regimes for the dependence of droplet size on activity. These results can provide a criterion for identifying the mechanisms responsible for arresting phase separation in experiments.

Characterization of the perioperative changes of exosomal immune-related cytokines induced by prostatectomy in early-stage prostate cancer patients.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are relevant in prostate cancer microenvironment collaborating in tumor development. The main tumor marker used in this disease, prostate-specific antigen (PSA), does not provide information related to this tumor microenvironment. Cancer cells secrete exosomes carrying bioactive molecules contributing to MDSCs recruitment and induction. The aim of this study was to characterize the perioperative changes of exosomal cytokines relevant in MDSCs recruitment induced by prostatectomy in prostate cancer patients. METHODS: Blood was drawn from 26 early-stage prostate cancer patients before and after radical prostatectomy and from 16 healthy volunteers. Serum exosomes were separated by precipitation. Cytokines related with MDSC cell recruitment and activation CCL2, CXCL2, CXCL5, CXCL8, CXCL12, MIF, S100A9 and TGF-ß were measured in serum and serum-derived exosomes using immunometric assays. RESULTS: All cytokines were detected both in serum and exosomes, except for CXCL12, which was detected only in serum. Exosomes were enriched specially in MIF, TGF-ß and CXCL2. Presurgical MIF levels in exosomes correlated negatively with serum PSA. Also, presurgical TGF-ß decreased both in serum and exosomes as Gleason score rises. Patients presurgical exosomes had increased CCL2, CXCL5 and TGF-ß levels than exosomes from healthy controls. These differences were not observed when cytokines were analyzed in serum, except for TGF-ß. Cytokine levels of CCL2, CXCL5 decreased in patients' postsurgical exosomes, while TGF-ß further increased. On the contrary, S100A9 levels were lower in patients presurgical exosomes but increased after radical prostatectomy. CONCLUSIONS: Blood exosomal content in cytokines constitute an attractive source to evaluate MDSCs immunomodulators providing additional information related to tumor microenvironment in prostate cancer.

Revealing importance of particles' surface functionalization on the properties of magnetic alginate hydrogels.

Iron/silica core-shell microparticles (IMPs) were functionalized by different functional groups including amine, glycidoxy, phenyl, and thiocyanate. Many of the IMPs modifications are reported for the first time. The resulting surface chemistry turned out to affect the properties of magnetic alginate hydrogels fabricated from sodium alginate and dispersed IMPs. Differences in magnetorheological properties of the obtained magnetic hydrogels can be at least partially attributed to the interactions between alginate and surface functionalities of IMPs. Density Functional Theory (DFT) calculations were carried out to get detailed insight into those interactions in order to link them with the observed macroscopic properties of the obtained hydrogels. For example, amine groups on the IMPs surface resulted in well-formed hydrogels while the presence of thiocyanate or phenyl groups - in poorly formed ones. This observation can be used for tuning the properties of various carbohydrate-based hydrogels.

Daily Pad Usage Versus the International Consultation on Incontinence Questionnaire Short Form for Continence Assessment Following Radical Prostatectomy.

PURPOSE: Continence assessment is an essential component of follow-up after radical prostatectomy (RP). Several methods exist to assess the severity of urinary incontinence (UI). Our study examined the relationship and degree of agreement between International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) scores and the number of pads used in a 24-hour period in the assessment of UI following RP. METHODS: Continence was prospectively assessed in 746 men from a Spanish urology clinic 12 months after RP using the ICIQ-SF and pad usage. The relationship between ICIQ-SF scores and pad usage was assessed using Spearman rank correlation coefficients. The Jonckheere-Terpstra trend test was used to determine whether the ICIQ-SF score and the component question scores increased with increasing pad usage. The Bonferroni-corrected pairwise Wilcoxon rank-sum test was used to determine which pairs of pad usage levels differed. The weighted kappa was used to evaluate the agreement between pad usage levels and ICIQ-SF questions. RESULTS: The continence rate was 82% using the "no pad usage" definition of continence versus 78% using the definition of an ICIQ-SF score of 0 (P<0.001). Strong positive correlations were observed between the number of pads and the ICIQ-SF total and component question scores (rs>0.85, P<0.001). The ICIQ-SF total and component question scores increased significantly with increasing pad usage (P<0.001). The ICIQ-SF scores (P<0.018) for all pairs of pad usage levels (0, 1, 2, or 3 or more) differed significantly. The agreement between the ICIQ-SF leakage amount question and pad usage was very good (rs=0.861, P<0.001). CONCLUSION: At 12 months post-RP, 24-hour pad usage was closely correlated with ICIQ-SF, although the continence rate differed depending on the definition used. Higher levels of pad usage were associated with higher questionnaire scores, more leakage, and poor quality of life (interference with everyday life).

Stealth Entropy Production in Active Field Theories near Ising Critical Points.

We address the steady-state entropy production rate (EPR) of active scalar ϕ^{4} theories, which lack time-reversal symmetry, close to a phase-separation critical point. We consider both nonconserved (model A) and conserved (model B) dynamics at Gaussian level, and also address the former at leading order in ε=4-d. In each case, activity is irrelevant in the RG sense: the active model lies in the same (dynamic Ising) universality class as its time-reversible counterpart. Hence one might expect that activity brings no new critical behavior. Here we show instead that, on approach to criticality in these models, the singular part of the EPR per (diverging) spacetime correlation volume either remains finite or itself diverges. A nontrivial critical scaling for entropy production thus ranks among universal dynamic Ising-class properties.

Searching for the erosion of empathy in medical undergraduate students: a longitudinal study.

OBJECTIVE: To analyse the trajectory of empathy throughout the degree programme of medicine in a Spanish school of medicine. DESIGN: Longitudinal, prospective 5-year study, between October 2014 and June 2019. SETTING: Students from a Spanish university of medicine. PARTICIPANTS: Two voluntary cohorts of undergraduate medical students from two different school years were invited to participate (n=135 (cohort 1, C1) and 106 (cohort 2, C2) per school year). Finally, a total number of 174 students (102 (C1, 71.6% women) and 72 (C2, 70.8% women) students, respectively) were monitored for 5 years. Each cohort was divided in two subcohorts of paired and unpaired students that were analysed to check possible social desirability bias. PRIMARY OUTCOME MEASURE: The Jefferson Scale of Empathy (JSE). RESULTS: The cohort of 102 students (C1) monitored between their first and fifth years of study (71.6% women) showed an improvement among paired women of 2.15 points in total JSE score (p=0.01) and 2.39 points in cognitive empathy (p=0.01); in the unpaired female cohort the increase was of 2.32 points (cognitive empathy) (p=0.02). The cohort of 72 students (C2) monitored between their second and sixth years of study (70.8% women) displayed a cognitive empathy increase of 2.32 points (p=0.04) in the paired group of women. There were no significant differences between paired and unpaired results for either cohort. Empathy scores among men did not decrease. CONCLUSIONS: The empathy of medical students at our school did not decline along grade years. In fact, it improved slightly, particularly cognitive empathy, among women. This paper contributes to enlarge data from Europe, where longitudinal studies are scarce. It supports the idea that there may be global geo-sociocultural differences; however, more studies comparing different school settings are needed.

A Robust Localization System for Inspection Robots in Sewer Networks.

Sewers represent a very important infrastructure of cities whose state should be monitored periodically. However, the length of such infrastructure prevents sensor networks from being applicable. In this paper, we present a mobile platform (SIAR) designed to inspect the sewer network. It is capable of sensing gas concentrations and detecting failures in the network such as cracks and holes in the floor and walls or zones were the water is not flowing. These alarms should be precisely geo-localized to allow the operators performing the required correcting measures. To this end, this paper presents a robust localization system for global pose estimation on sewers. It makes use of prior information of the sewer network, including its topology, the different cross sections traversed and the position of some elements such as manholes. The system is based on a Monte Carlo Localization system that fuses wheel and RGB-D odometry for the prediction stage. The update step takes into account the sewer network topology for discarding wrong hypotheses. Additionally, the localization is further refined with novel updating steps proposed in this paper which are activated whenever a discrete element in the sewer network is detected or the relative orientation of the robot over the sewer gallery could be estimated. Each part of the system has been validated with real data obtained from the sewers of Barcelona. The whole system is able to obtain median localization errors in the order of one meter in all cases. Finally, the paper also includes comparisons with state-of-the-art Simultaneous Localization and Mapping (SLAM) systems that demonstrate the convenience of the approach.

Pharmacological Chaperones for the Treatment of α-Mannosidosis.

α-Mannosidosis (AM) results from deficient lysosomal α-mannosidase (LAMAN) activity and subsequent substrate accumulation in the lysosome, leading to severe pathology. Many of the AM-causative mutations compromise enzyme folding and could be rescued with purpose-designed pharmacological chaperones (PCs). We found that PCs combining a LAMAN glycone-binding motif based on the 5 N,6 O-oxomethylidenemannojirimycin (OMJ) glycomimetic core and different aglycones, in either mono- or multivalent displays, elicit binding modes involving glycone and nonglycone enzyme regions that reinforce the protein folding and stabilization potential. Multivalent derivatives exhibited potent enzyme inhibition that generally prevailed over the chaperone effect. On the contrary, monovalent OMJ derivatives with LAMAN aglycone binding area-fitting substituents proved effective as activity enhancers for several mutant LAMAN forms in AM patient fibroblasts and/or transfected MAN2 B1-KO cells. This translated into a significant improvement in endosomal/lysosomal function, reverting not only the primary LAMAN substrate accumulation but also the additional downstream consequences such as cholesterol accumulation.

[Design and validation of a satisfaction questionnaire in patients with urolithiasis treated by extracorporeal shock wave lithotripsy (ESWL).] / Diseño y validación de un cuestionario de salud en pacientes con urolitiasis tratados mediante litotricia extracorpórea por ondas de choque (LEOC).

OBJECTIVES: Studying the psychosocial sphere of patients who undergo any treatment allows to have more information about its repercussion and can help the choice of an appropriate and personalized treatment. Due to the absence of specific instruments at present, the objective is to design and validate a health questionnaire regarding the treatment received with ESWL. METHODS: It was carried out in 6 phases using a sampleof 50 patients treated with ESWL in 2015 in ourcenter, whom we interviewed by telephone. In phase1 the items were proposed based on bibliographic review,in phase 2 those that scored below 7 were eliminatedaccording to the evaluation from 0 to 10 on theitems made by specialists. In phase 3, values of 1 to 5were assigned to each item and those with correctedcorrelation more than 0.2 and not significant (p>0.05)discriminant power with U-Mann Whitney were eliminated.In phase 4 the reliability of the questionnaire waschecked with two indexes (Cronbach's alpha and twoGuttman's halves). In phase 5, the factor analysis withVarimax rotation was performed to calculate the constructvalidity and in stage 6, the scores were analyzedto establish reference values. RESULTS: 50 patients (32 men, 18 women). Medianage 59 years (27-79). In phase 1, 35 items were proposed,9 of which were eliminated in phase 2. The initialquestionnaire with 26 items was distributed, with 18being eliminated in phase 3. The final questionnaire wasformed with 8 items. In phase 4 the results of Cronbach'salpha and Guttman's two halves index were 0.44 and0.323 respectively. In phase 5 after factor analysis, wefound 4 factors with 2 items each (background, impactof the acute picture, post-treatment, quality of life) able toexplain 71.19% of the variance. The median scores ofthe scale, extreme values and quartiles studied in phase6 were respectively: P50: 17 (minimum-maximum 9-25),P25: 14 and P75: 20. CONCLUSIONS: The study carried out has provided anew instrument for assessing satisfaction after treatmentwith ESWL with adequate reliability and validity values.Future studies will be necessary to contrast its true clinicalusefulness.

OBJETIVO: Estudiar la esfera psicosocial de los pacientes que se someten a algún tratamiento permite tener más información sobre la repercusión del mismo y puede ayudar a la elección de un tratamiento adecuado y personalizado. Debido a la ausencia deinstrumentos específicos actualmente, el objetivo es diseñary validar un cuestionario de salud en pacientes tratados con LEOC.MATERIAL Y MÉTODOS: Se realizó en 6 fases utilizando una muestra de 50 pacientes tratados con LEOC en 2015 en nuestro centro, a los que entrevistamos por vía telefónica. En la fase 1 se propusieron ítems a partir de revisión bibliográfica. En la fase 2 se eliminaron losque puntuaban por debajo de 7 según la valoración de 0-10 sobre los ítems efectuada por especialistas en la materia. En la fase 3 se asignaron valores de 1 a 5 a cada ítem y se eliminaron aquellos cuya correlación corregida fuera mayor de 0,2 y cuya potencia discriminante con U-Mann Whitney no fuera significativa (p>0,05). En la fase 4 se comprobó la fiabilidad del cuestionario con dos índices (alfa de Cronbach y dos mitades de Guttman). En la fase 5 se realizó el análisis factorial con rotación Varimax para el cálculo de la validez de constructo. Finalmente, en la fase 6 se tipificaron de las puntuaciones para establecer valores de referencia. RESULTADOS: 50 pacientes (32 hombres, 18 mujeres). Mediana edad 59 años (27-79). Fase 1: 35 ítems propuestos. Fase 2: 9 ítems eliminados. Distribución de cuestionario con 26 ítems. Fase 3: 18 ítems eliminados.Cuestionario final constituido por 8 ítems. Fase 4: valores de fiabilidad del cuestionario (alfa de Cronbach 0,44 e índice por técnica de dos mitades de Guttman 0,323). Fase 5: análisis factorial hallando 4 factores con 2 ítems cada uno (antecedentes, repercusión delcuadro agudo, post-tratamiento, calidad de vida) capaces de explicar el 71,19% de la varianza. Fase 6: mediana puntuación  50:17(mínimo-máximo 9-25), P25:14 y P75:20. CONCLUSIONES: El trabajo realizado ha proporcionado un nuevo instrumento de evaluación de salud tras tratamiento con LEOC con valores de fiabilidad y validez adecuados. Serán necesarios futuros estudios para contrastar su verdadera utilidad clínica.

Diseño y validación de un cuestionario de salud en pacientes con urolitiasis tratados mediante litotricia extracorpórea por ondas de choque (LEOC) / No disponible

Objetivo: Estudiar la esfera psicosocial de los pacientes que se someten a algún tratamiento permite tener más información sobre la repercusión del mismo y puede ayudar a la elección de un tratamiento adecuado y personalizado. Debido a la ausencia de instrumentos específicos actualmente, el objetivo es diseñar y validar un cuestionario de salud en pacientes tratados con LEOC. Material y métodos: Se realizó en 6 fases utilizando una muestra de 50 pacientes tratados con LEOC en 2015 en nuestro centro, a los que entrevistamos por vía telefónica. En la fase 1 se propusieron ítems a partir de revisión bibliográfica. En la fase 2 se eliminaron los que puntuaban por debajo de 7 según la valoración de 0-10 sobre los ítems efectuada por especialistas en la materia. En la fase 3 se asignaron valores de 1 a 5 a cada ítem y se eliminaron aquellos cuya correlación corregida fuera mayor de 0,2 y cuya potencia discriminante con U-Mann Whitney no fuera significativa (p>0,05). En la fase 4 se comprobó la fiabilidad del cuestionario con dos índices (alfa de Cronbach y dos mitades de Guttman). En la fase 5 se realizó el análisis factorial con rotación Varimax para el cálculo de la validez de constructo. Finalmente, en la fase 6 se tipificaron de las puntuaciones para establecer valores de referencia. Resultados: 50 pacientes (32 hombres, 18 mujeres). Mediana edad 59 años (27-79). Fase 1: 35 ítems propuestos. Fase 2: 9 ítems eliminados. Distribución de cuestionario con 26 ítems. Fase 3: 18 ítems eliminados. Cuestionario final constituido por 8 ítems. Fase 4: valores de fiabilidad del cuestionario (alfa de Cronbach 0,44 e índice por técnica de dos mitades de Guttman 0,323). Fase 5: análisis factorial hallando 4 factores con 2 ítems cada uno (antecedentes, repercusión del cuadro agudo, post-tratamiento, calidad de vida) capaces de explicar el 71,19% de la varianza. Fase 6: mediana puntuación 50:17(mínimo-máximo 9-25), P25:14 y P75:20. Conclusiones: El trabajo realizado ha proporcionado un nuevo instrumento de evaluación de salud tras tratamiento con LEOC con valores de fiabilidad y validez adecuados. Serán necesarios futuros estudios para contrastar su verdadera utilidad clínica

Objectives: Studying the psychosocial sphere of patients who undergo any treatment allows to have more information about its repercussion and can help the choice of an appropriate and personalized treatment. Due to the absence of specific instruments at present, the objective is to design and validate a health questionnaire regarding the treatment received with ESWL. Methods: It was carried out in 6 phases using a sample of 50 patients treated with ESWL in 2015 in our center, whom we interviewed by telephone. In phase 1 the items were proposed based on bibliographic review, in phase 2 those that scored below 7 were eliminated according to the evaluation from 0 to 10 on the items made by specialists. In phase 3, values of 1 to 5 were assigned to each item and those with corrected correlation more than 0.2 and not significant (p>0.05) discriminant power with U-Mann Whitney were eliminated. In phase 4 the reliability of the questionnaire was checked with two indexes (Cronbach’s alpha and two Guttman's halves). In phase 5, the factor analysis with Varimax rotation was performed to calculate the construct validity and in stage 6, the scores were analyzed to establish reference values. Results: 50 patients (32 men, 18 women). Median age 59 years (27-79). In phase 1, 35 items were proposed, 9 of which were eliminated in phase 2. The initial questionnaire with 26 items was distributed, with 18 being eliminated in phase 3. The final questionnaire was formed with 8 items. In phase 4 the results of Cronbach’s alpha and Guttman’s two halves index were 0.44 and 0.323 respectively. In phase 5 after factor analysis, we found 4 factors with 2 items each (background, impact of the acute picture, post-treatment, quality of life) able to explain 71.19% of the variance. The median scores of the scale, extreme values and quartiles studied in phase 6 were respectively: P50: 17 (minimum-maximum 9-25), P25: 14 and P75: 20. Conclusions: The study carried out has provided a new instrument for assessing satisfaction after treatment with ESWL with adequate reliability and validity values. Future studies will be necessary to contrast its true clinical usefulness

Validation of the Jefferson Scale of Physician Empathy in Spanish medical students who participated in an Early Clerkship Immersion programme.

BACKGROUND: The Jefferson Scale of Physician Empathy is the most widely used instrument to measure empathy in the doctor-patient relationship. This work pursued cultural adaptation and validation of the original scale, in its health professions version (JSE-HP), for medical students who participate in an Early Clerkship Immersion Programme of a Spanish university. METHODS: The questionnaire was replied by 506 1st, 2nd, 3rd and 5th year medical students from Universidad Francisco de Vitoria, Madrid, in 2014 and 2016. Internal consistency was analysed by means of Cronbach's alpha, and reliability by means of test-retest using the intraclass correlation coefficient and the Bland-Altman method. The construct validity was checked by means of confirmatory factor analysis and association with other empathy-related variables. Criterion validity was compared using Davis' Interpersonal Reactivity Index. RESULTS: Cronbach's alpha was 0.82 (range 0.80-0.85). Item-total score correlations were positive and significant (median 0.45, p <  0.01). The test-retest intraclass correlation coefficient was 0.68 (0.42-0.82). The factor analysis confirmed the three original factors: "perspective taking", "compassionate care" and "standing in the patient's shoes". Women and students who preferred specialities focused on persons obtained the best scores. The JSE-HP scores were positively correlated with Interpersonal Reactivity Index, personality traits were associated with empathy, clinical interview skills and Objective Structured Clinical Examinations. CONCLUSION: The results support the validity and reliability of JSE-HP applied to Spanish medical students.

Strong Coupling in Conserved Surface Roughening: A New Universality Class?

The Kardar-Parisi-Zhang (KPZ) equation defines the main universality class for nonlinear growth and roughening of surfaces. But under certain conditions, a conserved KPZ equation (CKPZ) is thought to set the universality class instead. This has non-mean-field behavior only in spatial dimension d<2. We point out here that CKPZ is incomplete: It omits a symmetry-allowed nonlinear gradient term of the same order as the one retained. Adding this term, we find a parameter regime where the one-loop renormalization group flow diverges. This suggests a phase transition to a new growth phase, possibly ruled by a strong-coupling fixed point and thus described by a new universality class, for any d>1. In this phase, numerical integration of the model in d=2 gives clear evidence of non-mean-field behavior.

[The role of chemotherapy in the treatment of hormone sensitive metastatic prostate cancer.] / Papel de la quimioterapia en el tratamiento del cáncer de próstata metastásico hormonosensible.

OBJECTIVE: Several studies have assessed the role of adding chemotherapy to hormonal treatment for metastatic hormone-sensitive prostate cancer (MHSPC). The objective of this manuscript is to review these studies and to provide recommendations for the management of these patients. METHODS: We identified published clinical trials comparing hormone blockade (HB) with HB plus docetaxel as first-line treatment of HSMPC and we analyzed their results in terms of efficacy and toxicity. RESULTS: Of the 3 trials published, two demonstrated increased overall survival by adding docetaxel to the first-line treatment of MHSPC (CHAARTED and Stampede-Docetaxel studies) and the third one did not show such an advantage (GETUG-AFU15). In the CHAARTED study, the survival advantage was limited to patients presenting high tumor volume. Toxicity was increased in patients who received docetaxel. CONCLUSIONS: The addition of docetaxel to treatment with HB should be considered in patients with MHSPC, especially in those with high tumor volume. However, the toxicity and recent results of trials performed with abiraterone in MHSPC should also be taken in consideration.