Multiview Landmark Detection for Identity-preserving Alignment

Projecte realitzat en el marc d’un programa de mobilitat amb la KTH Royal Institute of Technology[ANGLÈS] Face recognition is a fundamental task in computer vision and has been an important field of study for many years. This report presents a unified process for automatically extract a set of face landmarks and remove all differences related to pose, expression and environment by bringing faces to a neutral pose-centered state. Landmark detection is based on a multiple viewpoint Pictorial Structure model. In this project we address both the problem of how to find a set of landmarks from a model and the problem of training such a model from a set of labelled examples. We show how such a model successfully captures a great range of deformations needing far less training examples than common commercial face detectors. The alignment process basically aims to remove differences between multiple faces so they all can be analysed under the same criteria. It is carried out with Thin-plate Splines to adjust the detected set of landmarks to the desired configuration. We present results of our algorithms both in a constrained environment and in the challenging LFPW face database. Successful outcomes are shown that prove our method to be a solid process for unitedly recognise and warp faces in the wild and to be on a par with other state-of-the-art procedures.[CASTELLÀ] El reconocimiento y clasificación de caras representa uno de los campos de estudio más importantes dentro la visión artificial por computadora y el procesado de imagen. En este proyecto se presenta un proceso unificado que extrae automáticamente, a partir de imágenes, un conjunto de puntos faciales característicos, eliminando al mismo tiempo las diferencias relacionadas con la orientación, expresión e iluminación. En una primera fase, se utiliza un modelo de Estructuras Pictográficas Multivista para la detección de puntos característicos. En este informe, se atienden con detalle tanto el problema de extraer puntos con este modelo, como el proceso de aprendizaje a partir de imágenes anotadas. En una segunda fase, se eliminan las diferencias entre caras mediante el uso de Thin-Plate Splines, para que todas las imágenes puedan ser analizadas bajo el mismo criterio en posibles aplicaciones futuras. Los algoritmos implementados, representan hasta la fecha, el primer sistema desarrollado, que simultáneamente extrae y alinea caras, y demuestran un comportamiento muy fiable y preciso tanto en entornos controlados como libres (base de datos LFPW).[CATALÀ] reconeixement i classificació de cares és un dels camps d'estudi més importants dintre la visió artificial per computadora i el processament d'imatge. En aquest projecte es presenta un procés unificat que extreu automàticament, a partir d'imatges, un conjunt de punts facials característics eliminant al mateix temps les diferències relacionades amb l'orientació, expressió i il·luminació. En una primera fase, s'utilitza un model d'Estructures Pictogràfiques Multivista per a la detecció de punts característics. En aquest informe, s'adreça amb detall tant el problema d'extreure punts amb aquest model com el procés d'aprenentatge a partir d'imatges anotades. En una segona fase, s'eliminen les diferències entre cares mitjançant Thin-Plate Splines, per tal que totes les imatges puguin ser analitzades sota el mateix criteri en possibles aplicacions futures. Els algoritmes implementats, representen fins al moment, el primer sistema desenvolupat que unificadament extreu i alinea cares, i demostren un comportament molt fiable i acurat tant en entorns controlats com lliures (base de dades LFPW)

Motivacions, expectatives i objectius del professorat en les visites als museus de ciència

[cat] La tesi planteja com a pregunta de recerca quines són les motivacions, les expectatives i els objectius del professorat a l’hora d’organitzar visites als museus i centres de ciència amb els seus alumnes. Per respondre la pregunta, la finalitat principal es proposava conèixer, descriure i categoritzar les característiques del centres i dels docents, les seves motivacions per visitar el museu, les expectatives quant al vincle amb el currículum i al model didàctic i els objectius que tenen pel que fa al moment de desenvolupament del tema en què es produeix la visita. Atesos els canvis produïts al museu objecte de la investigació entre les dues fases de la recerca, es pretenia també saber els possibles modificacions en el perfil dels docents i les seves motivacions, expectatives i objectius, de cara a definir els factors que han de ser tinguts en compte a l’hora de desenvolupar el model didàctic del museu. El marc teòric sobre el que se sustenta parteix de l’anàlisi de la literatura que ens mostra la percepció que tenen els ciutadans sobre la ciència i les idees que orienten l’educació científica al segle XXI, continua amb l’anàlisi de l’educació als museus i els models de museus de ciència segons la seva proposta didàctica i finalitza amb l’anàlisi dels treballs que s’han portat a terme arreu sobre motivacions, expectatives i objectius dels docents quan porten els seus alumnes als museus de ciència. La investigació portada a terme es pot considerar descriptiva, amb un objectiu avaluatiu i atenent a les variables recollides, de caire ex-post-facto. L’obtenció de dades ha combinat la metodologia quantitativa en base a una enquesta de preguntes tancades a 308 docents i la metodologia qualitativa basada en entrevistes semiestructurades a 7 experts en gestió de museus i formació del professorat, un grup de discussió amb educadors del museu i 10 docents usuaris del museu. La recollida de dades es va realitzar els anys 2008 i 2012 entre els quals el museu va patir un gran canvi. L’anàlisi de les dades quantitatives de l’enquesta ha estat desenvolupat a partir del tractament estadístic realitzat amb el programari SPSS V.13 a partir del qual es van obtenir estadístics descriptius i es van aplicar proves d'estadística inferencial paramètriques i no paramètriques. En el cas de les dades qualitatives, es va realitzar la transcripció completa de les entrevistes i del grup de discussió Per poder analitzar les respostes, es va seguir un procediment d’anàlisi fenomenològic, creant una base de dades Access 2007 extraient unitats de significat rellevants que van ser codificades amb codis descriptius agrupats en famílies i aquestes en grups de significat. Els resultats obtinguts han estat discutits amb els referents de la literatura examinada al marc teòric i també amb l’opinió dels experts expressada a la fase I. En aquest sentit es destaquen aquells aspectes que la nostra recerca corrobora o contradiu, així com les noves aportacions que fa en l’àmbit de les motivacions, expectatives i objectius dels docents. Hem observat alguns comportaments comuns a diferents llocs del Món i, a la vegada, una gran diversitat de situacions que fan molt complexa la realització d’activitats en un museu de ciències. Aquest fet ens ha portat a desenvolupar recomanacions d’actuació tant en el camp de la gestió del servei educatiu del museu com en la didàctica emprada en les activitats. Es proposen també algunes línies de recerca que poden derivar de la tesi Finalment s’extreuen conclusions que, en síntesi, indiquen que el museu ha de treballar col·laborativament amb l’escola ja que no n’és un simple complement curricular. L’educació científica escolar pateix d’uns dèficits descrits al marc teòric malgrat les moltes experiències de centres educatius concrets que trenquen la rutina. En aquest sentit, el museu aporta per la seva part una manera de fer que, en col·laboració amb l’escola, pot determinar nous enfocaments innovadors.[eng] The thesis research question arises as to what are the motivations, expectations and objectives of teachers in organizing visits to science museums with their students. The main purpose was to know, describe and categorize the characteristics of schools and teachers, their motivations for visiting the museum, expectations regarding the link with the curriculum and teaching model and the goals they have for the moment in which the visit occurs. Given the changes in the museum under investigation between the two phases of the research, it was intended also to know the possible evolution in the profile of teachers and the research question in order to define the factors that must be taken into account when developing the teaching model of the museum. The theoretical framework begins with the ideas that guide science education in the XXI century and the analysis of the models of education in science museums. The study of the international researches that has been carried out about motivations, expectations and objectives of teachers is the basis for the analysis and discussion of the results. The research may be considered descriptive, with a goal to assessment and ex-post-facto. The data collection combined the quantitative methodology based on a survey to 308 teachers and the qualitative methodology based on semi-structured interviews to an amount of 17 experts and teachers. It was conducted in 2008 and 2012. The analysis of the survey data was developed from the statistical treatment performed with SPSS V.13 software from which it was obtained descriptive statistics and parametric and non-parametric statistical inference testing were applied. For the qualitative data, the full transcript of the interviews was realized to analyze the responses, following a phenomenological analysis procedure, creating an Access 2007 database by extracting relevant units of meaning that were encoded with descriptive codes grouped into families and those in groups of meaning. The results have been discussed with related literature and the experts’ opinion expressed in phase I. In this regard we highlight those aspects of our research that corroborates or contradicts them, as well as new contributions in the field of motivations, expectations and objectives of teachers. We noticed some common behaviour in different parts of the world and at the same time, a variety of complex situations when carrying out activities in a science museum. This has led us to develop recommendations for action both in the management of the museum's educational service as in teaching activities. It is also proposed some new researches that may result from the thesis. Finally, conclusions for each research question are drawn, in short, indicating that the museum should work collaboratively with the school because the museum is not only a curricular complement. The scientific education school suffers from deficits described in the theoretical framework despite the many experiences of specific schools that break the routine. The museum meanwhile, provides a way to do that in co-operation with the school that can determine new innovative approaches

Allogeneic Stem Cell Transplantation with CD34+ Cell Selection

PB received funding a PERIS 2018-2020 grant from the Generalitat de Catalunya (BDNS357800). MAP received funding from the National Institutes of Health (Grant P01 CA23766 and NIH/NCI cancer Center Support Grant P30 CA008748).The success of allogeneic stem cell transplant is hampered by the development of acute and chronic graft- versus -host disease (GvHD) which has direct impact on treatment-related mortality and morbidity. As a result, T cell depletion through positive selection of CD34+ cells has emerged as a promising strategy to reduce acute and chronic GvHD in these patients. In this review, we summarize the main characteristics of allogeneic stem cell transplant with CD34+ cell selection including risks of graft failure, GvHD, infection, organ toxicity, and long-term survival. Moreover, we highlight future strategies to improve the results of this platform and to consolidate its use in clinical practice

Outcomes for patients with EBV-positive PTLD post-allogeneic HCT after failure of rituximab-containing therapy

Enfermedad linfoproliferativa; Virus de Epstein-BarrMalaltia limfoproliferativa; Virus d'Epstein-BarrLymphoproliferative disease; Epstein-Barr virusEpstein–Barr virus-positive (EBV+) post-transplant lymphoproliferative disease (PTLD) is an ultra-rare and aggressive condition that may occur following allogeneic hematopoietic cell transplant (HCT) due to immunosuppression. Approximately half of EBV+ PTLD cases are relapsed or refractory (R/R) to initial rituximab-containing therapy. There are limited treatment options and no standard of care for patients with R/R EBV+ PTLD, and little is known about their treatment history and outcomes. We performed a multinational, multicenter, retrospective chart review of patients with R/R EBV+ PTLD following HCT to describe patients’ demographic and disease characteristics, treatment history, and overall survival (OS) from rituximab failure. Among 81 patients who received initial treatment with rituximab as monotherapy (84.0%) or in combination with chemotherapy (16.0%), median time from HCT to PTLD diagnosis was 3.0 months and median OS was 0.7 months. Thirty-six patients received a subsequent line of treatment. The most frequent causes of death were PTLD (56.8%), graft-versus-host disease (13.5%) and treatment-related mortality (10.8%). In multivariate analysis, early PTLD onset and lack of response to initial treatment were associated with mortality. This real-world study demonstrates that the prognosis of patients with R/R EBV+ PTLD following HCT remains poor, highlighting the urgent unmet medical need in this population

Safety and feasibility of stem cell boost as a salvage therapy for severe hematotoxicity after CD19 CAR T-cell therapy

Stem cell; Hematotoxicity; T-cellCélulas madre; Hematotoxicidad; Células TCèl·lules mare; Hematotoxicitat; Cèl·lules TThis work was supported by a fellowship from School of Oncology of German Cancer Consortium (DKTK) (K.R.) and was funded by the Else Kröner Forschungskolleg; a Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) research grant provided within the Sonderforschungbereich (SFB-TRR 388/1 2021–452881907) and DFG research grant (451580403) (M.S.); the Bavarian Elite Graduate Training Network (M.S.), the Wilhelm-Sander Stiftung (project no. 2018.087.1) (M.S.), the Else-Kröner-Fresenius Stiftung (M.S., K.R., V. Bücklein, V. Blumenberg), and the Bavarian Center for Cancer Research (BZKF)

Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion

Hematotoxicity; Suppressive immune dysregulationHematotoxicidad; Desregulación inmunesupresoraHematotoxicitat; Desregulació immunesupressoraProlonged cytopenias after chimeric antigen receptor (CAR) T cell therapy are a significant clinical problem and the underlying pathophysiology remains poorly understood. Here, we investigated how (CAR) T cell expansion dynamics and serum proteomics affect neutrophil recovery phenotypes after CD19-directed CAR T cell therapy. Survival favored patients with “intermittent” neutrophil recovery (e.g., recurrent neutrophil dips) compared to either “quick” or “aplastic” recovery. While intermittent patients displayed increased CAR T cell expansion, aplastic patients exhibited an unfavorable relationship between expansion and tumor burden. Proteomics of patient serum collected at baseline and in the first month after CAR-T therapy revealed higher markers of endothelial dysfunction, inflammatory cytokines, macrophage activation, and T cell suppression in the aplastic phenotype group. Prolonged neutrophil aplasia thus occurs in patients with systemic immune dysregulation at baseline with subsequently impaired CAR-T expansion and myeloid-related inflammatory changes. The association between neutrophil recovery and survival outcomes highlights critical interactions between host hematopoiesis and the immune state stimulated by CAR-T infusion.K.Rej. received a fellowship from the School of Oncology of the German Cancer Consortium (DKTK) and was funded by the Else Kröner Forschungskolleg (EKFK) within the Munich Clinician Scientist Program (MCSP). This work was supported by a grant within the Gilead Research Scholar Program (to K.Rej. and M.S.), the Bruno & Helene Jöster Foundation (to K.R., M.S.), and by a Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) research grant provided within the Sonderforschungbereich SFB-TRR 338/1 2021 – 452881907 and DFG research grant 451580403 (to M.S.). The work was further supported by the Bavarian Elite Graduate Training Network (to M.S.), the Wilhelm-Sander Stiftung (to M.S., project no. 2018.087.1), the Else-Kröner-Fresenius Stiftung (to M.S.), and the Bavarian Cancer Research Center (BZKF)

The CAR-HEMATOTOX score identifies patients at high risk for hematological toxicity, infectious complications, and poor treatment outcomes following brexucabtagene autoleucel for relapsed or refractory MCL

Hematological toxicity; Infectious complicationsToxicidad hematológica; Complicaciones infecciosasToxicitat hematològica; Complicacions infecciosesCD19-directed CAR T-cell therapy with brexucabtagene autoleucel (brexu-cel) has substantially improved treatment outcomes for patients with relapsed/refractory mantle cell lymphoma (r/r MCL). Prolonged cytopenias and infections represent common and clinically relevant side effects. In this multicenter observational study, we describe cytopenias and infections in 103 r/r MCL patients receiving brexu-cel. Furthermore, we report associations between the baseline CAR-HEMATOTOX (HT) score and toxicity events, non-relapse mortality (NRM), and progression-free/overall survival (PFS/OS). At lymphodepletion, 56 patients were HTlow (score 0–1) while 47 patients were HThigh (score ≥2). The HThigh cohort exhibited prolonged neutropenia (median 14 vs. 6 days, p < .001) and an increased rate of severe infections (30% vs. 5%, p = .001). Overall, 1-year NRM was 10.4%, primarily attributed to infections, and differed by baseline HT score (high vs. low: 17% vs. 4.6%, p = .04). HThigh patients experienced inferior 90-day complete response rate (68% vs. 93%, p = .002), PFS (median 9 months vs. not-reached, p < .0001), and OS (median 26 months vs. not-reached, p < .0001). Multivariable analyses showed that high HT scores were independently associated with severe hematotoxicity, infections, and poor PFS/OS. In conclusion, infections and hematotoxicity are common after brexu-cel and contribute to NRM. The baseline HT score identified patients at increased risk of poor treatment outcomes.KR received a fellowship from the School of Oncology of the German Cancer Consortium (DKTK) and was funded by the Else Kröner Forschungskolleg (EKFK) within the Munich Clinician Scientist Program (MCSP). This work was supported by a grant within the Gilead Research Scholar Program (to KR, MS), the Bruno & Helene Jöster foundation (to KR, MS), and by a Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) research grant provided within the Sonderforschungbereich SFB-TRR 388/12021–452881907 and DFG research grant 451580403 (to MS). This work was in part supported by NCI/NIH P30CA076292. FLL is in part supported as a Clinical Scholar by the Leukemia and Lymphoma Society. The work was further supported by the Bavarian Elite Graduate Training Network (to MS), the Wilhelm-Sander Stiftung (to MS, project no. 2018.087.1), the Else-Kröner-Fresenius Stiftung (to MS), and the Bavarian Center for Cancer Research (BZKF)

Prognostic heterogeneity of adult B-cell precursor acute lymphoblastic leukaemia patients with t(1;19)(q23;p13)/TCF3-PBX1 treated with measurable residual disease-oriented protocols

Acute lymphoblastic leukaemia; Cytogenetic alterations; PrognosisLeucemia linfoblástica aguda; Alteraciones citogenéticas; PronósticoLeucèmia limfoblàstica aguda; Alteracions citogenètiques; PronòsticThe prognosis of t(1;19)(q23;p13)/transcription factor 3-pre-B-cell leukaemia homeobox 1 (TCF3-PBX1) in adolescent and adult patients with acute lymphoblastic leukaemia (ALL) treated with measurable residual disease (MRD)-oriented trials remains controversial. In the present study, we analysed the outcome of adolescent and adult patients with t(1;19)(q23;p13) enrolled in paediatric-inspired trials. The patients with TCF3-PBX1 showed similar MRD clearance and did not have different survival compared with other B-cell precursor ALL patients. However, patients with TCF3-PBX1 had a significantly higher cumulative incidence of relapse, especially among patients aged ≥35 years carrying additional cytogenetic alterations. These patients might benefit from additional/intensified therapy (e.g. immunotherapy in first complete remission with or without subsequent haematopoietic stem cell transplantation).This work was supported in part by CERCA/Generalitat de Catalunya SGR 2017 288 (GRC), a restricted grant from ‘La Caixa’ and Healthcare Alliance for Resourceful Medicine Offensive against Neoplasms (HARMONY)

Quantifying the available capacity and resource needs for provision of CAR-T therapies in the National Health Service in Spain: a survey-based study

Leukaemia; Organisation of health services; TherapeuticsLeucemia; Organización de servicios de salud; TerapéuticaLeucèmia; Organització dels serveis sanitaris; TerapèuticaObjectives To estimate the readiness of Spanish National Health Service (NHS) hospitals to provide chimeric antigen receptor T cell (CAR-T), and to identify and quantify the different resources needed to provide CAR-T considering three scenarios defined by 10, 25 and 50 patients per centre per year. Design Targeted literature review and quantitative study using a questionnaire and telephone interviews. An algorithm was created to determine hospitals’ readiness based on their capacity and capability. All the requirements for quantification were assessed and validated by the steering committee, formed by members of the Spanish Group of Haematopoietic Transplantation and Cell Therapy. A weighting system (from 0 to 1) was established for capability quantification. For resources quantification, a scoring system was established, with 0 points representing the minimum and 3 points the maximum of additional resources that a hospital indicated necessary. Setting 40 Spanish hospital centres that perform allogeneic haematopoietic stem cell transplantation were invited to complete the questionnaire for capacity quantification, 28 of which provided valid responses. Nine hospitals participated in the interviews for resource quantification, eight of which had previously been designated by the Ministry of Health (MoH) to provide CAR-T. Outcome measure Current capacity of NHS Spanish sites to administer CAR-T under different theoretical scenarios with varying numbers of procedures, and the potential healthcare resources that would be needed to realise the theoretical capacity requirements. Results Four hospitals were optimally ready, 17 were somewhat ready and 7 were not ready. The actual extrapolated capacity of the currently designated MoH CAR-T sites would allow treatment of approximately 250 patients per year. Regarding healthcare resource needs, the numbers of haematologists, nurses and beds were the most important limiting factors, and those requiring further growth as patient numbers increased. Conclusions Increasing the number of CAR-T-qualified centres and/or increasing resources in the current designated sites are two potential strategies that should be considered to treat CAR-T-eligible patients in Spain.This study was conducted with a grant from GETH-TC (grant number: N/A)

Superior survival with pediatric-style chemotherapy compared to myeloablative allogeneic hematopoietic cell transplantation in older adolescents and young adults with Ph-negative acute lymphoblastic leukemia in first complete remission: analysis from CALGB 10403 and the CIBMTR

Acute lymphocytic leukaemia; ChemotherapyLeucemia linfocítica aguda; QuimioterapiaLeucèmia limfocítica aguda; QuimioteràpiaOptimal post-remission therapy for adolescents and young adults (AYAs) with Ph-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR1) is not established. We compared overall survival (OS), disease-free survival (DFS), relapse, and non-relapse mortality (NRM) for patients receiving post-remission therapy on CALGB 10403 to a cohort undergoing myeloablative (MA) allogeneic hematopoietic cell transplantation (HCT) in CR1. In univariate analysis, OS was superior with chemotherapy compared to MA allogeneic HCT (3-year OS 77% vs. 53%, P < 0.001). In multivariate analysis, allogeneic HCT showed inferior OS (HR 2.00, 95% CI 1.5–2.66, P < 0.001), inferior DFS (HR 1.62, 95% CI 1.25–2.12, P < 0.001), and increased NRM (HR 5.41, 95% CI 3.23–9.06, P < 0.001) compared to chemotherapy. A higher 5-year relapse incidence was seen with chemotherapy compared to allogeneic HCT (34% vs. 23%, P = 0.011). Obesity was independently associated with inferior OS (HR 2.17, 95% CI 1.63–2.89, P < 0.001), inferior DFS (HR 1.97, 95% CI 1.51–2.57, P < 0.001), increased relapse (1.84, 95% CI 1.31–2.59, P < 0.001), and increased NRM (HR 2.10, 95% CI 1.37–3.23, P < 0.001). For AYA ALL patients in CR1, post-remission therapy with pediatric-style chemotherapy is superior to MA allogeneic HCT for OS, DFS, and NRM