Evaluation of factors leading to poor outcomes for pediatric acute lymphoblastic leukemia in Mexico: a multi-institutional report of 2,116 patients

Background and aimsPediatric acute lymphoblastic leukemia (ALL) survival rates in low- and middle-income countries are lower due to deficiencies in multilevel factors, including access to timely diagnosis, risk-stratified therapy, and comprehensive supportive care. This retrospective study aimed to analyze outcomes for pediatric ALL at 16 centers in Mexico.MethodsPatients <18 years of age with newly diagnosed B- and T-cell ALL treated between January 2011 and December 2019 were included. Clinical and biological characteristics and their association with outcomes were examined.ResultsOverall, 2,116 patients with a median age of 6.3 years were included. B-cell immunophenotype was identified in 1,889 (89.3%) patients. The median white blood cells at diagnosis were 11.2.5 × 103/mm3. CNS-1 status was reported in 1,810 (85.5%), CNS-2 in 67 (3.2%), and CNS-3 in 61 (2.9%). A total of 1,488 patients (70.4%) were classified as high-risk at diagnosis. However, in 52.5% (991/1,889) of patients with B-cell ALL, the reported risk group did not match the calculated risk group allocation based on National Cancer Institute (NCI) criteria. Fluorescence in situ hybridization (FISH) and PCR tests were performed for 407 (19.2%) and 736 (34.8%) patients, respectively. Minimal residual disease (MRD) during induction was performed in 1,158 patients (54.7%). The median follow-up was 3.7 years. During induction, 191 patients died (9.1%), and 45 patients (2.1%) experienced induction failure. A total of 365 deaths (17.3%) occurred, including 174 deaths after remission. Six percent (176) of patients abandoned treatment. The 5-year event-free survival (EFS) was 58.9% ± 1.7% for B-cell ALL and 47.4% ± 5.9% for T-cell ALL, while the 5-year overall survival (OS) was 67.5% ± 1.6% for B-cell ALL and 54.3% ± 0.6% for T-cell ALL. The 5-year cumulative incidence of central nervous system (CNS) relapse was 5.5% ± 0.6%. For the whole cohort, significantly higher outcomes were seen for patients aged 1–10 years, with DNA index >0.9, with hyperdiploid ALL, and without substantial treatment modifications. In multivariable analyses, age and Day 15 MRD continued to have a significant effect on EFS.ConclusionOutcomes in this multi-institutional cohort describe poor outcomes, influenced by incomplete and inconsistent risk stratification, early toxic death, high on-treatment mortality, and high CNS relapse rate. Adopting comprehensive risk-stratification strategies, evidence-informed de-intensification for favorable-risk patients and optimized supportive care could improve outcomes

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Mesure fonctionnelle appliquée aux principaux problèmes sociaux en Colombie : drogues, sexe, violence et pardon

Colombia is located in northwestern portion South America. Currently, 46 million people inhabit the country and are mainly concentrated in the cities. According to the National Administrative Department of Statistics (2017), the population distribution is mainly explained by the forced displacement of persons resulting from the Colombian armed conflict that lasted nearly 60 years (from 1960 to 2015). In the present thesis, four problems of particular interest are examined: education for preventing drug use, sexual education, the capacity to forgive in situations of medical negligence, and the capacity to forgive acts of violence perpetrated against women in the context of the Colombian armed conflict. In the first study on the willingness of Colombian adults to forgive, Colombians have difficulties in integrating stimuli at the moment of deciding whether to forgive in a political context, yet it is not easy for them to forgive in a political context compared to other situations such as medical negligence. About the second study, polarization and the invisibility of victims are also common themes with respect to crimes committed against women. The study identified that the willingness to forgive of the participants is low. However, only a small group of participants consider the crime itself upon contemplating forgiveness, while another small group consider the attitude of the aggressor. In regard to the education of young people to prevent drug use, it is important to highlight that many subjects are still taboo in Colombia. As shown by the data, prohibitionist and authoritarian standpoints on drug use are considered to be the most acceptable. In regard to sexual education, the majority of young people in Colombia do not have access to such education despite this being a basic right. Likewise, parents and caretakers are apparently unable to effectively and assertively educate their children on this topic.La Colombie est un pays situé dans le nord-ouest de l’Amérique du Sud. La plupart de ses 46 millions d’habitants sont concentrés dans les villes. Selon le Département Administratif National des Statistiques (2017), la répartition de la population s’explique par le déplacement forcé des personnes, causé par le conflit armé qui a duré presque 60 ans (de 1960 à 2015). Dans la présente thèse, quatre problèmes d’un intérêt particulier sont examinés : l’éducation pour prévenir la consommation des drogues, l’éducation sexuelle, la capacité de pardon dans des situations de négligence des soins et la capacité de pardon des actes de violence perpétués contre les femmes dans le contexte du conflit armé colombien. Cette étude a identifié que la volonté de pardon des participants est faible. Cependant, un petit groupe de participants seulement accorde une importance au crime lui-même concernant le pardon, tandis qu’un autre petit groupe, accorde plus d’importance à l’attitude de l’agresseur. Concernant l’éducation des jeunes en vue de prévenir la consommation des drogues, il est important de souligner qu’il existe encore plusieurs sujets tabous en Colombie. Selon les données de l’étude, les points de vue prohibitionniste et autoritaire concernant la consommation des drogues sont les plus partagés. S’agissant de l’éducation sexuelle, la plupart de jeunes en Colombie n’y ont pas accès, bien qu’il s’agisse d’un droit fondamental. De plus, les parents ou les personnes en situation de parentalité semblent être incapables d’éduquer leurs enfants efficacement et assertivement au regard de ce sujet

Prueba T- Student

Este recurso educativo habla acerca de la prueba T- Student que verifica las diferencias entre las medias de dos grupos diferentes que tengan distribución normal y homogeneidad en sus variables. También sustenta diferentes explicaciones frente a la manera adecuada de realizar estas pruebas las cuales sirven para analizar y comparar.Este OVA presenta algunas de las características de la prueba t-Student aplicada a los diseños de investigación, su desarrollo en SPSS y la interpretación de los datos1. Introducción2. Prueba T de Student3. Supuestos de la prueba T de Student4. Prueba T de Student para muestras independientes5. Grados de libertad6. Un ejemplo con SPSS7. Prueba T de Student para muestras relacionadas8. Actividad de práctica8.1. En el programa estadístico8.2. Resuelva1.0This OVA presents some of the characteristics of the t-Student test applied to research designs, its development in SPSS and the interpretation of dataPsicologoPregrad

Supuestos

En este recurso se habla sobre los supuestos como criterios que se deben cumplir para cada uno de los modelos estadísticos.El objetivo de esta práctica es proporcionar a los estudiantes la oportunidad de realizar pruebas paramétricas encontrando la distribución normal y la homogeneidad de la variable que indica la diferencia del promedio que hay entre cada uno de los valores con respecto a su punto central.1. Introducción2. ¿Qué son los supuestos?3. Supuestos para los datos paramétricos4. Homogeneidad de la varianza5. Actividad de aprendizaje6. Referencias1.0The objective of this practice is to provide students the opportunity to perform parametric tests by finding the normal distribution and homogeneity of the variable that indicates the difference of the average between each of the values with respect to its point central.PsicologoPregrad

Evaluación de un programa de formación de padres para el desarrollo socioemocional en la infancia

Magíster en PsicologíaMaestrí