Tratamiento en primera línea de mieloma múltiple no candidato a trasplante: experiencia y evolución en 5 años de un hospital terciario

PO-011 Introducción: El avance en tratamiento del mieloma múltiple en las últimas décadas ha supuesto mejoría en las tasas de supervivencia y en las posibilidades de manejo en pacientes de edad avanzada o con comorbilidad. Estudios realizados han demostrado la eficacia de nuevos esquemas de tratamiento con lenalidomida o bortezomib asociados o no al tratamiento clásico con melfalán. Objetivos: Describir los esquemas de tratamiento utilizados en pacientes con reciente diagnóstico de mieloma sintomático en primera línea en la práctica clínica habitual en pacientes no candidatos a trasplante. Observar la tendencia en los últimos cinco años y asociarla con las guías de práctica clínica. Analizar la supervivencia libre de progresión en primera línea. Métodos: estudio observacional, descriptivo y retrospectivo realizado en el H. U. Miguel Servet de Zaragoza desde abril 2014 hasta abril 2019. Se incluyeron pacientes con nuevo diagnóstico de mieloma múltiple sintomático no candidatos a trasplante en primera línea (según criterios de IMWG). Los criterios de exclusión fueron: haber recibido tratamiento previo y no disponibilidad de datos determinantes para el estudio. ..

Child stunting is associated with weaker human capital among native Amazonians

Unidad de excelencia María de Maeztu MdM-2015-0552Objectives:We assessed associations between child stunting, recovery, and faltering with schooling and human capital skills in a native Amazonian society of horticulturalists-foragers (Tsimane'). - Methods: We used cross-sectional data (2008) from 1262 children aged 6 to 16 years in 53 villages to assess contemporaneous associations between three height categories: stunted (height-for-age Z score, HAZ-1), and three categories of human capital: completed grades of schooling, test-based academic skills (math, reading, writing), and local plant knowledge. We used annual longitudinal data (2002-2010) from all children (n = 853) in 13 villages to estimate the association between changes in height categories between the first and last years of measure and schooling and academic skills. - Results: Stunting was associated with 0.4 fewer completed grades of schooling (∼24% less) and with 13-15% lower probability of showing any writing or math skills. Moderate stunting was associated with ∼20% lower scores in local plant knowledge and 9% lower probability of showing writing skills, but was not associated with schooling or math and writing skills. Compared with nonstunted children, children who became stunted had 18-21% and 15-21% lower probabilities of showing math and writing skills, and stunted children had 0.4 fewer completed grades of schooling. Stunted children who recovered showed human capital outcomes that were indistinguishable from nonstunted children. Conclusions: The results confirm adverse associations between child stunting and human capital skills. Predictors of growth recovery and faltering can affect human capital outcomes, even in a remote, economically self-sufficient society

Multi-particle azimuthal correlations in p-Pb and Pb-Pb collisions at the CERN Large Hadron Collider

Measurements of multi-particle azimuthal correlations (cumulants) for charged particles in p-Pb and Pb-Pb collisions are presented. They help address the question of whether there is evidence for global, flow-like, azimuthal correlations in the p-Pb system. Comparisons are made to measurements from the larger Pb-Pb system, where such evidence is established. In particular, the second harmonic two-particle cumulants are found to decrease with multiplicity, characteristic of a dominance of few-particle correlations in p-Pb collisions. However, when a $|\Delta \eta|$ gap is placed to suppress such correlations, the two-particle cumulants begin to rise at high-multiplicity, indicating the presence of global azimuthal correlations. The Pb-Pb values are higher than the p-Pb values at similar multiplicities. In both systems, the second harmonic four-particle cumulants exhibit a transition from positive to negative values when the multiplicity increases. The negative values allow for a measurement of $v_{2}\{4\}$ to be made, which is found to be higher in Pb-Pb collisions at similar multiplicities. The second harmonic six-particle cumulants are also found to be higher in Pb-Pb collisions. In Pb-Pb collisions, we generally find $v_{2}\{4\} \simeq v_{2}\{6\}\neq 0$ which is indicative of a Bessel-Gaussian function for the $v_{2}$ distribution. For very high-multiplicity Pb-Pb collisions, we observe that the four- and six-particle cumulants become consistent with 0. Finally, third harmonic two-particle cumulants in p-Pb and Pb-Pb are measured. These are found to be similar for overlapping multiplicities, when a $|\Delta\eta| > 1.4$ gap is placed.Comment: 25 pages, 11 captioned figures, 3 tables, authors from page 20, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/87

Multiplicity dependence of jet-like two-particle correlations in p-Pb collisions at sNN\sqrt{s_{NN}} = 5.02 TeV

Two-particle angular correlations between unidentified charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum range 0.7 $< p_{\rm{T}, assoc} < p_{\rm{T}, trig} <$ 5.0 GeV/$c$ is examined, to include correlations induced by jets originating from low momen\-tum-transfer scatterings (minijets). The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range $|\eta|<0.9$. The near-side long-range pseudorapidity correlations observed in high-multiplicity p-Pb collisions are subtracted from both near-side short-range and away-side correlations in order to remove the non-jet-like components. The yields in the jet-like peaks are found to be invariant with event multiplicity with the exception of events with low multiplicity. This invariance is consistent with the particles being produced via the incoherent fragmentation of multiple parton--parton scatterings, while the yield related to the previously observed ridge structures is not jet-related. The number of uncorrelated sources of particle production is found to increase linearly with multiplicity, suggesting no saturation of the number of multi-parton interactions even in the highest multiplicity p-Pb collisions. Further, the number scales in the intermediate multiplicity region with the number of binary nucleon-nucleon collisions estimated with a Glauber Monte-Carlo simulation.Comment: 23 pages, 6 captioned figures, 1 table, authors from page 17, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/161

A note on comonotonicity and positivity of the control components of decoupled quadratic FBSDE

In this small note we are concerned with the solution of Forward-Backward Stochastic Differential Equations (FBSDE) with drivers that grow quadratically in the control component (quadratic growth FBSDE or qgFBSDE). The main theorem is a comparison result that allows comparing componentwise the signs of the control processes of two different qgFBSDE. As a byproduct one obtains conditions that allow establishing the positivity of the control process.Comment: accepted for publicatio

MHC Hammer reveals genetic and non-genetic HLA disruption in cancer evolution

Disruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss of heterozygosity (LOH), allele-specific mutation and measurement of expression and repression (MHC Hammer). We identified extensive variability in HLA allelic expression and pervasive HLA alternative splicing in normal lung and breast tissue. In lung TRACERx and lung and breast TCGA cohorts, 61% of lung adenocarcinoma (LUAD), 76% of lung squamous cell carcinoma (LUSC) and 35% of estrogen receptor-positive (ER+) cancers harbored class I HLA transcriptional repression, while HLA tumor-enriched alternative splicing occurred in 31%, 11% and 15% of LUAD, LUSC and ER+ cancers. Consistent with the importance of HLA dysfunction in tumor evolution, in LUADs, HLA LOH was associated with metastasis and LUAD primary tumor regions seeding a metastasis had a lower effective neoantigen burden than non-seeding regions. These data highlight the extent and importance of HLA transcriptomic disruption, including repression and alternative splicing in cancer evolution

Mieloma múltiple extra-óseo, un caso con mala evolución ¿es lo usual?

PB-021 Introducción: El mieloma extramedular (MEM) se presenta al diagnóstico en 3-18% de los casos y otro 10-30% lo padecerá en algún en la evolución. Esta presentación de MM se asocia a morfología inmadura, Cg de alto riesgo, escape de cadenas ligeras, disminución en la expresión de CD56y aumento en la expresión de CD44 y CXCR4; con peor pronóstico pese a los avances en el tratamiento. Metodologia: Presentamos el caso de un paciente con diagnóstico de MM IgA K extra óseo con una evolución desfavorable. Diagnóstico inicial en Febrero 2014 ISS I, con plasmocitoma en V, VIII y IX arco costal, recibió tratamiento con VD por 6 ciclos alcanzando RC y posteriormente TASPE y consolidación con Velcade por 6 ciclos. Primer recaída en Ago 2016 con masa en pared torácica sin contacto óseo; escape a CLL K, tratamiento con VRD por 6 ciclos logrando RC y segundo TASPE y mantenimiento con R. Segunda recaída en Mayo 2018 con derrame pleural y ascitis maligna, tratamiento con DVd por 1 ciclo y progresión intratratamiento; cambio a Pomalidomida-Claritromicina- Dexametasona sin respuesta, desarrollo de insuficiencia respiratoria, fallo renal y hepático culminando en su fallecimiento en Agosto 2018. Conclusiones: Acorde a lo reportado, la supervivencia de la paciente fue menor a lo esperado por escalas de riesgo (ER) habitual (ISS) y el grado de respuesta alcanzado con el tratamiento, la SG fue de 54 meses con SLP 31 meses, la supervivencia después de la segunda recaída fue de 3 meses, similar a lo ya descrito (6 meses). Acorde a un estudio realizado por Weinstock el MEM solo 1, 32% de los MEM se manifestaron con enfermedad pleural y derrame, y 0, 62% en peritoneo y ascitis (como en el caso). Al igual que lo reportado, la enfermedad de la paciente presentó liberación de cadenas ligeras. Si bien existe evidencia y ..

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Spatiotemporal Dynamics of Genetic Variation in the Iberian Lynx along Its Path to Extinction Reconstructed with Ancient DNA

There is the tendency to assume that endangered species have been both genetically and demographically healthier in the past, so that any genetic erosion observed today was caused by their recent decline. The Iberian lynx (Lynx pardinus) suffered a dramatic and continuous decline during the 20th century, and now shows extremely low genome- and specieswide genetic diversity among other signs of genomic erosion. We analyze ancient (N¼10), historical (N¼245), and contemporary (N¼172) samples with microsatellite and mitogenome data to reconstruct the species’ demography and investigate patterns of genetic variation across space and time. Iberian lynx populations transitioned from low but significantly higher genetic diversity than today and shallow geographical differentiation millennia ago, through a structured metapopulation with varying levels of diversity during the last centuries, to two extremely genetically depauperate and differentiated remnant populations by 2002. The historical subpopulations show varying extents of genetic drift in relation to their recent size and time in isolation, but these do not predict whether the populations persisted or went finally extinct. In conclusion, current genetic patterns were mainly shaped by genetic drift, supporting the current admixture of the two genetic pools and calling for a comprehensive genetic management of the ongoing conservation program. This study illustrates how a retrospective analysis of demographic and genetic patterns of endangered species can shed light onto their evolutionary history and this, in turn, can inform conservation actions

Secuencia de tratamiento óptima para el tratamiento del mieloma múltiple en España un modelo secuencial

PO-014 Introducción: El mieloma múltiple (MM) se sigue considerando una enfermedad incurable. Sin embargo, con la disponibilidad de nuevos fármacos, las opciones de tratamiento para pacientes de MM han incrementado drásticamente, aumentando a su vez su supervivencia. Esto hace que sea necesario evaluar la secuencia de tratamiento más apropiada, en lugar de los regímenes de manera aislada. Junto con la seguridad y la eficacia, la evaluación económica se está convirtiendo en una herramienta cada vez más útil y necesaria en la toma de decisiones. Objetivos: El estudio tiene como objetivo estimar los beneficios y costes de las secuencias de tratamiento en el MM más comunes para establecer un umbral de eficiencia y determinar la ratio coste-eficacia incremental (ICER) entre las secuencias. Métodos: Se diseñó un modelo de Markov con 5 estados de salud que representan líneas de tratamiento (1ª, 2ª, 3ª y posteriores) y muerte, con 3 subestados relacionados con la respuesta (respuesta completa [CR], respuesta parcial [PR] y no respuesta [NR]) para simular la transición de pacientes (cada 4 semanas) a lo largo del curso de la enfermedad. Un consejo de hematólogos definió veinte posibles secuencias de tratamiento, como las más utilizadas en la práctica clínica en España. Una revisión de la literatura permitió la identificación de los estudios para estimar las tasas de respuesta específica de cada terapia y los eventos adversos (EA), junto con el tiempo de progresión dependiente de la respuesta requerido para modelar la transición entre las líneas terapéuticas sucesivas y los valores de utilidad necesarios para evaluar la calidad de vida de los pacientes para poder estimar la variable principal del estudio ..