Preparing for low surface brightness science with the Vera C. Rubin Observatory: a comparison of observable and simulated intracluster light fractions

Intracluster light (ICL) provides an important record of the interactions galaxy clusters have undergone. However, we are limited in our understanding by our measurement methods. To address this, we measure the fraction of cluster light that is held in the Brightest Cluster Galaxy and ICL (BCG+ICL fraction) and the ICL alone (ICL fraction) using observational methods (surface brightness threshold-SB, non-parametric measure-NP, composite models-CM, and multi-galaxy fitting-MGF) and new approaches under development (wavelet decomposition-WD) applied to mock images of 61 galaxy clusters (14 <log10M200c/M⊙ < 14.5) from four cosmological hydrodynamical simulations. We compare the BCG+ICL and ICL fractions from observational measures with those using simulated measures (aperture and kinematic separations). The ICL fractions measured by kinematic separation are significantly larger than observed fractions. We find the measurements are related and provide equations to estimate kinematic ICL fractions from observed fractions. The different observational techniques give consistent BCG+ICL and ICL fractions but are biased to underestimating the BCG+ICL and ICL fractions when compared with aperture simulation measures. Comparing the different methods and algorithms, we find that the MGF algorithm is most consistent with the simulations, and CM and SB methods show the smallest projection effects for the BCG+ICL and ICL fractions, respectively. The Ahad (CM), MGF, and WD algorithms are best set up to process larger samples; however, the WD algorithm in its current form is susceptible to projection effects. We recommend that new algorithms using these methods are explored to analyse the massive samples that Rubin Observatory’s Legacy Survey of Space and Time will provide

Preparing for low surface brightness science with the Vera C. Rubin Observatory: A Comparison of Observable and Simulated Intracluster Light Fractions

Intracluster Light (ICL) provides an important record of the interactions galaxy clusters have undergone. However, we are limited in our understanding by our measurement methods. To address this we measure the fraction of cluster light that is held in the Brightest Cluster Galaxy and ICL (BCG+ICL fraction) and the ICL alone (ICL fraction) using observational methods (Surface Brightness Threshold-SB, Non-Parametric Measure-NP, Composite Models-CM, Multi-Galaxy Fitting-MGF) and new approaches under development (Wavelet Decomposition-WD) applied to mock images of 61 galaxy clusters (14<log10 M_200c/M_solar <14.5) from four cosmological hydrodynamical simulations. We compare the BCG+ICL and ICL fractions from observational measures with those using simulated measures (aperture and kinematic separations). The ICL fractions measured by kinematic separation are significantly larger than observed fractions. We find the measurements are related and provide equations to estimate kinematic ICL fractions from observed fractions. The different observational techniques give consistent BCG+ICL and ICL fractions but are biased to underestimating the BCG+ICL and ICL fractions when compared with aperture simulation measures. Comparing the different methods and algorithms we find that the MGF algorithm is most consistent with the simulations, and CM and SB methods show the smallest projection effects for the BCG+ICL and ICL fractions respectively. The Ahad (CM), MGF and WD algorithms are best set up to process larger samples, however, the WD algorithm in its current form is susceptible to projection effects. We recommend that new algorithms using these methods are explored to analyse the massive samples that Rubin Observatory's Legacy Survey of Space and Time will provide.Comment: Submitted for publication in MNRAS, posted to arXiv after responding to two positive rounds of referee comments. Key results in Figs 3, 5, 6 and 1

CD200 genotype is associated with clinical outcome of patients with multiple myeloma

Immune dysfunction in patients with MM affects both the innate and adaptive immune system. Molecules involved in the immune response pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of immune checkpoint molecules in predicting the myeloma control and immunological scape as mechanism of disease progression. We retrospectively analyzed the clinical impact of the CD200 genotype (rs1131199 and rs2272022) in 291 patients with newly diagnosed MM. Patients with a CD200 rs1131199 GG genotype showed a median overall survival (OS) significantly lower than those with CC+CG genotype (67.8 months versus 94.4 months respectively; p: 0.022) maintaining significance in the multivariate analysis. This effect was specially detected in patients not receiving an autologous stem cell transplant (auto-SCT) (p < 0.001). In these patients the rs1131199 GG genotype negatively influenced in the mortality not related with the progression of MM (p: 0.02) mainly due to infections events

Investigación en matemáticas, economía y ciencias sociales

El resultado de este libro que reune inquietudes académicas en torno a temas tan estudiados como los que están alrededor del maíz, del frijol o del café; y tan contemporáneos como las aplicaciones concretas de las ciencias ya citadas, al estudio de la adopción del comercio electrónico en empresas del sector agroindustrial o, el caso de la generación de biogas o energía eléctrica por medio de biodigestores. Al editar este texto e incorporarlo a la bibliografía de los temas de referencia, se enriquecen opciones de consulta para los estudiosos de esos temas en general; pero también para interesados en aspectos tan específicos como la cadena de suministro del mercado hortofrutícola en Texcoco

Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma

Immune dysfunction in patients with multiple myeloma (MM) affects both the innate and adaptive immune system. Molecules involved in the immune checkpoint pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of these molecules in predicting the kinetics of progression of MM. We retrospectively analysed polymorphisms of CTLA4 (rs231775 and rs733618), BTLA (rs9288953), CD28 (rs3116496), PD-1 (rs36084323 and rs11568821) and LAG-3 (rs870849) genes in 239 patients with newly diagnosed MM. Patients with a CTLA4 rs231775 AA/AG genotype showed a median progression-free survival (PFS) significantly lower than those with GG genotype (32.3 months versus 96.8 months respectively; p: 0.008). The 5-year PFS rate was 25% for patients with grouped AA and AG genotype vs 55.4% for patients with GG genotype. Multivariate analysis confirmed the CTLA4 rs231775 genotype as an independent risk factor for PFS (Hazard Ratio (HR): 2.05; 95% CI: 1.0-6.2; p: 0.047). Our results suggest that the CTLA4 genotype may identify patients with earlier progression of MM. This polymorphism could potentially be used as a prognostic biomarker

Polimorfismos de los genes moduladores de la respuesta inmune como predictores de recaída en los pacientes con mieloma múltiple

Multiple myeloma (MM) remains an incurable disease despite the incorporation of new therapies. The natural history of disease is of the relapse following treatments due to the re-emergence of the tumour from residual disease that cannot be eradicated, significantly reducing the life expectancy of these patients. Cellular and humoral immune impairment is a feature of MM evolution, allowing neoplastic plasma cells to escape from natural immune surveillance. The immune system is a powerful defense mechanism against cancer; it can recognize and attack premalignant cells before tumours develop (immune surveillance). The adaptive immune response is regulated by multiple co-stimulatory and co-inhibitory signaling pathways. The balance between co-stimulatory and co-inhibitory signals, immune checkpoints, determines the functionally of T cells during immunity and tolerance. However, few data are available concerning the role of immune surveillance in preventing o controlling myeloma relapse in patients with MM. In this direction, we explored the polymorphisms (SNPs) of genes that encode co-stimulatory/inhibitory molecules of the immune response and evaluated their impact on overall survival (OS) and progression free survival (PFS). In the first study, we retrospectively analysed polymorphisms of CTLA4 (rs231775 and rs733618), BTLA (rs9288953), CD28 (rs3116496), PD-1 (rs36084323 and rs11568821) y LAG-3 (rs870849) genes in 239 patients with newly diagnosed MM. Patients with a CTLA4 rs231775 AA/AG genotype showed a median PFS significantly lower than those with GG genotype, this negative effect was especially evident in patients who have received an autologous transplant. Our results suggest that the CTLA4 genotype may identify patients with earlier progression of MM. This polymorphism could potentially be used as a prognostic biomarker. In the second study, we focused on the analysis of genetic variants of CD200. Several studies have shown that overexpression of CD200 in MM cells is associated with worse survival, however there are not data concerning the correlation between genetic variants of CD200 and survival in patients with MM. We retrospectively analysed the clinical impact of the of CD200 genotype (rs1131199 and rs2272022) in 291 patients with newly diagnosed MM. We did not find any significant difference of expression of CD200 in the MM cells between the different genotypes for each polymorphism studied. Patients with a CD200 rs1131199 GG genotype showed a median OS significantly lower than those with CC+CG genotype. This effect was specially detected in patients not receiving an auto-TPH. In these patients, the rs1131199 GG genotype negatively influenced in the mortality not related with the progression of MM mainly due to infections events. This polymorphism could potentially identify patients at high risk of mortality associated with infectionsEl mieloma múltiple (MM) continua essent una malaltia incurable malgrat la incorporació de noves teràpies. La historia natural del MM es la recaiguda desprès dels successius tractaments degut a la reaparició del tumor a partir de la malaltia residual que no ha pogut ser eliminada, veient-se reduïda la seva esperança de vida de forma significativa. Durant la progressió del MM, es produeixen defectes de la immunitat cel·lular i humoral que contribueixen a l’escapament de la cèlul.la tumoral del control immune natural. El sistema immune es un potent mecanisme de defensa contra el càncer, es capaç de reconèixer i destruir les cèl·lules premalignes abans de que els tumors es formin (la vigilància immune). La resposta immune adaptativa està estretament regulada per múltiples vies coestimuladores i inhibitòries. L´equilibri entre senyals de co-estimulació i d´inhibició, punts de control immunològic, determina la funcionalitat de les cèl·lules T durant la immunitat i la tolerància. Fins ara, es disposa de molt poques dades sobre el paper del sistema immune per a la prevenció o el control de la recidiva tumoral en els pacients amb MM. En aquest context, en aquesta tesis explorem els polimorfismes (SNPs) de gens que codifiquen molècules de coestimulació/inhibició de la resposta immune i avaluem el seu impacte en la supervivència global (SG) i supervivència lliure de progressió (SLP). En el primer treball que compon la tesis, s´han analitzat retrospectivament polimorfismes genètics de CTLA4 (rs231775 i rs733618), BTLA (rs9288953), CD28 (rs3116496), PD-1 (rs36084323 i rs11568821) i LAG-3 (rs870849) en 239 pacients amb MM de nou diagnòstic. Els pacients amb genotip CTLA4 rs231775 AA/AG van mostrar una mitjana de SLP significativament menor que els pacients portadors del genotip GG, essent més evident aquest efecte negatiu en els pacients que han rebut un trasplantament autòleg (auto-TPH). Els nostres resultats suggereixen que la presencia de genotips específics en el gen de CTLA4 pot identificar pacients amb alt risc de progressió precoç. Aquest polimorfisme podria ser potencialment usat com a un biomarcador pronòstic. El segon treball s´ha centrat en l’anàlisi de les variants genètiques del gen de CD200. Varis estudis han demostrat que la sobre-expressió de CD200 a la cèlul.la plasmàtica tumoral s´associa a una pitjor supervivència, però, no hi ha estudis que correlacionin variants genètiques del gen de CD200 amb supervivència en pacients amb MM. S’han analitzat retrospectivament polimorfismes genètics de CD200 (rs1131199 i rs2272022) en 291 pacients amb MM de nou diagnòstic. No es van observar diferencies d´expressió de CD200 a les cèl·lules plasmàtiques entre els diferents genotips per a cada un dels polimorfismes estudiats. Els pacients amb genotip CD200 rs1131199 GG van mostrar una mitjana de SG significativament menor que els pacients portadors del genotip CC+CG. Aquest efecte es especialment detectat en els pacients que no van rebre un auto-TPH. En aquests pacients, el genotip CD200 rs1131199 GG influeix negativament a la mortalitat no relacionada amb la progressió principalment la deguda a les infeccions. Aquest polimorfisme potencialment identificaria pacients d'alt risc de mortalitat associada a les infeccionsPrograma de Doctorat en Biologia Molecular, Biomedicina i Salu

Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma

Immune dysfunction in patients with multiple myeloma (MM) affects both the innate and adaptive immune system. Molecules involved in the immune checkpoint pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of these molecules in predicting the kinetics of progression of MM. We retrospectively analysed polymorphisms of CTLA4 (rs231775 and rs733618), BTLA (rs9288953), CD28 (rs3116496), PD-1 (rs36084323 and rs11568821) and LAG-3 (rs870849) genes in 239 patients with newly diagnosed MM. Patients with a CTLA4 rs231775 AA/AG genotype showed a median progression-free survival (PFS) significantly lower than those with GG genotype (32.3 months versus 96.8 months respectively; p: 0.008). The 5-year PFS rate was 25% for patients with grouped AA and AG genotype vs 55.4% for patients with GG genotype. Multivariate analysis confirmed the CTLA4 rs231775 genotype as an independent risk factor for PFS (Hazard Ratio (HR): 2.05; 95% CI: 1.0-6.2; p: 0.047). Our results suggest that the CTLA4 genotype may identify patients with earlier progression of MM. This polymorphism could potentially be used as a prognostic biomarker

Oral ixazomib-dexamethasone vs oral pomalidomide-dexamethasone for lenalidomide-refractory, proteasome inhibitor-exposed multiple myeloma: a randomized Phase 2 trial

Multiple myeloma (MM) patients typically receive several lines of combination therapy and first-line treatment commonly includes lenalidomide. As patients age, they become less tolerant to treatment, requiring convenient/tolerable/lenalidomide-free options. Carfilzomib and/or bortezomib-exposed/intolerant, lenalidomide-refractory MM patients with &gt;= 2 prior lines of therapy were randomized 3:2 to ixazomib-dexamethasone (ixa-dex) (n = 73) or pomalidomide-dexamethasone (pom-dex) (n = 49) until progression/toxicity. Median progression-free survival (mPFS) was 7.1 vs 4.8 months with ixa-dex vs pom-dex (HR 0.847, 95% CI 0.535-1.341, P = 0.477; median follow-up: 15.3 vs 17.3 months); there was no statistically significant difference between arms. In patients with 2 and &gt;= 3 prior lines of therapy, respectively, mPFS was 11.0 vs 5.7 months (HR 1.083, 95% CI 0.547-2.144) and 5.7 vs 3.7 months (HR 0.686, 95% CI 0.368-1.279). Among ixa-dex vs pom-dex patients, 69% vs 81% had Grade &gt;= 3 treatment-emergent adverse events (TEAEs), 51% vs 53% had serious TEAEs, 39% vs 36% had TEAEs leading to drug discontinuation, 44% vs 32% had TEAEs leading to dose reduction, and 13% vs 13% died on study. Quality of life was similar between arms and maintained during treatment. Ixa-dex represents an important lenalidomide-free, oral option for this heavily pretreated, lenalidomide-refractory, proteasome inhibitor-exposed population

Table_1_Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma.docx

Immune dysfunction in patients with multiple myeloma (MM) affects both the innate and adaptive immune system. Molecules involved in the immune checkpoint pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of these molecules in predicting the kinetics of progression of MM. We retrospectively analysed polymorphisms of CTLA4 (rs231775 and rs733618), BTLA (rs9288953), CD28 (rs3116496), PD-1 (rs36084323 and rs11568821) and LAG-3 (rs870849) genes in 239 patients with newly diagnosed MM. Patients with a CTLA4 rs231775 AA/AG genotype showed a median progression-free survival (PFS) significantly lower than those with GG genotype (32.3 months versus 96.8 months respectively; p: 0.008). The 5-year PFS rate was 25% for patients with grouped AA and AG genotype vs 55.4% for patients with GG genotype. Multivariate analysis confirmed the CTLA4 rs231775 genotype as an independent risk factor for PFS (Hazard Ratio (HR): 2.05; 95% CI: 1.0-6.2; p: 0.047). Our results suggest that the CTLA4 genotype may identify patients with earlier progression of MM. This polymorphism could potentially be used as a prognostic biomarker.</p

Table_1_CD200 genotype is associated with clinical outcome of patients with multiple myeloma.docx

Immune dysfunction in patients with MM affects both the innate and adaptive immune system. Molecules involved in the immune response pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of immune checkpoint molecules in predicting the myeloma control and immunological scape as mechanism of disease progression. We retrospectively analyzed the clinical impact of the CD200 genotype (rs1131199 and rs2272022) in 291 patients with newly diagnosed MM. Patients with a CD200 rs1131199 GG genotype showed a median overall survival (OS) significantly lower than those with CC+CG genotype (67.8 months versus 94.4 months respectively; p: 0.022) maintaining significance in the multivariate analysis. This effect was specially detected in patients not receiving an autologous stem cell transplant (auto-SCT) (p < 0.001). In these patients the rs1131199 GG genotype negatively influenced in the mortality not related with the progression of MM (p: 0.02) mainly due to infections events.</p