Chimerism in Myeloid Malignancies following Stem Cell Transplantation Using FluBu4 with and without Busulfan Pharmacokinetics versus BuCy

In the era of precision medicine, the impact of personalized dosing of busulfan is not clear. We undertook a retrospective analysis of 78 patients with myeloid malignancies who received fludarabine and busulfan (FluBu4) with or without measuring Bu pharmacokinetics (Bu PK) and those who received busulfan with cyclophosphamide (BuCy). Fifty-five patients received FluBu4, of whom 21 had Bu PK measured, and 23 patients received BuCy. Total donor cell chimerism showed that the percentage of patients maintaining 100% donor chimerism on day 100 was 66.7%, 38.2%, and 73.9% in the FluBu4 with PK, FluBu4 with no PK, and BuCy, respectively (P = .001). Patients who had decreasing donor chimerism by day 100 were 23.8%, 52.9%, and 26.1% in the FluBu4 with PK, FluBu4 with no PK, and BuCy, respectively (P = .04). Bu PK group had fewer patients with less than 95% donor chimerism on day 30, which was not statistically significant, 5% (FluBu4 PK), 31% (FluBu4 with no PK), and 21% (BuCy) (P = .18). Survival distributions were not statistically significant (P = .11). Thus, personalized drug dosing can impact donor chimerism in myeloid malignancies. This will need to be examined in larger retrospective multicenter studies and prospective clinical trials

Treinamento e Desenvolvimento em IES: a experiência na estruturação de um programa de qualidade no atendimento ao público no campus de Bauru da UNESP.

Este artigo visa instigar a reflexão sobre as atuais e acentuadas transformações sentidas na sociedade contemporânea, em especial no mundo do trabalho, bem como destacar a importância da implementação de ações voltadas ao aprimoramento e capacitação profissional dos trabalhadores, como estratégia imprescindível para o acompanhamento dessas transformações e o atendimento de novas demandas presentes. Ressalta a importância de essas ações serem planejadas por equipe multiprofissional, em que o Psicólogo Organizacional e do Trabalho tem papel relevante. Objetiva também apresentar o caso de uma recente experiência no planejamento de um modelo de Programa de Treinamento e Desenvolvimento voltado para a melhoria da qualidade de atendimento ao público da Universidade Estadual Paulista – UNESP - Campus de Bauru

Prenatal Detection of Congenital Heart Diseases: One-Year Survey Performing a Screening Protocol in a Single Reference Center in Brazil

Objective. To describe the experience of a tertiary center in Brazil to which patients are referred whose fetuses are at increased risk for congenital heart diseases (CHDs). Methods. This was a cross-sectional observational study. The data was collected prospectively, during the year 2012, through a screening protocol of the fetal heart adapted from the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) guideline. We performed a fetal echocardiogram screening for all pregnant women who were referred to the fetal cardiology outpatient obstetrics clinic of a university hospital. The exams were classified as normal or abnormal. The cases considered abnormal were undergone to a postnatal echocardiogram. We categorized the abnormal fetal heart according to severity in “complex,” “significant,” “minor,” and “others.” Results. We performed 271 fetal heart screening. The incidence of abnormal screenings was 9.96% (27 fetuses). The structural CHD when categorized due to severity showed 48.1% (n=13) of “complex” cases, 18.5% (n=5) “significant” cases, and 7.4% (n=2) “minor” cases. The most common referral reason was by maternal causes (67%) followed by fetal causes (33%). The main referral indication was maternal metabolic disease (30%), but there was just one fetus with CHD in such cases (1.2%). CHDs were found in 19/29 fetuses with suspicion of some cardiac abnormality by obstetrician (65.5%). Conclusion. We observed a high rate of CHD in our population. We also found that there was higher incidence of complex cases

Detection of X-ray Resonance Scattering in Active Stellar Coronae

An analysis of Lyman series lines arising from hydrogen-like oxygen and neon ions in the coronae of the active RS CVn-type binaries II Peg and IM Peg, observed using the {\it Chandra} High Resolution Transmission Grating Spectrograph, shows significant decrements in the Ly$\alpha$/Ly$\beta$ ratios as compared with theoretical predictions and with the same ratios observed in similar active binaries. We interpret these decrements in terms of resonance scattering of line photons out of the line-of-sight; these observations present the first strong evidence for this effect in active stellar coronae. The net line photon loss implies a non-uniform and asymmetric surface distribution of emitting structures on these stars. Escape probability arguments, together with the observed line ratios and estimates of the emitting plasma density, imply typical line-of-sight sizes of the coronal structures that dominate the X-ray emission of $10^{10}$ cm at temperatures of $3\times 10^6$ K and of $10^8$ cm at $10^7$ K. These sizes are an order of magnitude larger than predicted by simple quasi-static coronal loops models, but are still very small compared to the several $10^{11}$ cm radii of the underlying stars.Comment: Accepted for publication on ApJ Letters. 14 pages, 2 figure

Update on a pilot study: Flumeltbi peripheral blood HLAhaploidentical stem cell transplantation with post-transplant cyclophosphamide and bortezomib (Cy2Bor3)

Background: Bortezomib (Bor) can inhibit the proliferation of dendritic cells (DCs) and block the expression of co-receptors CD80, CD86 and secretion of cytokines IL-12 and TNF-α and hence the ability of DCs to activate T cells. We started a pilot study incorporating the addition of bortezomib to post-transplant cyclophosphamide (PTCY) in the setting of peripheral blood (PB) HLA-haploidentical stem cell transplantation (Haplo-SCT). Methods: This is a single center open label pilot study. Eligible patients received Fludarabine Melphalan TBI 200 cGy as conditioning followed by haplo-SCT and PTCY. Bor was administered at 1.3mg/m2 on day+1, 4 and 7. Tacrolimus and MMF were started at day+5. Results: Seven patients were enrolled so far, five males and 2 females. Median age was 58 years (26-60). Donors were 3 brothers, 3 sons and 1 mother. Disease risk index was high in 3, intermediate in 3 and low in 1. Three patients had AML, two had ALL and MM, one had ALL and one had CML. CMV recipient status was negative in one and positive in 6. Median HCT-CI was 3(1-4). Median CD34 and CD3 infused were 4.13 x10-6 and 1.7x10-8/ kg recipient respectively, all were cryopreserved except 2. Four patients had CRS before Cy infusion with ASTCT grade of 1. Six patients had grade 3 hypokalemia around day+ 4-5. Five patients had grade 3 mucositis and 2 had grade 1. Four patients had neutropenic fever and one patient had engraftment fever. Median neutrophils and platelets engraftment were 16 and 26 days respectively. Chimerism post SCT was \u3e =99% donor at day 30 for all patients. Six patients are off tacrolimus with median time to be off it was 187.5 days. Five pts had aGVHD with maximum grade of I in 3 patients, II in one patient and III in one patient at a median 50days post SCT. None developed early hematuria, four had late hematuria with highest grade of 4. Two patients were positive for BK virus. One patient had reactivation of CMV, 2 had EBV and one had adenovirus, all resolved. Three pts had HHV6 that resolved. Of the 5 patients who were evaluable, one developed moderate chronic GVHD. So far the median time to follow up is 455 days (70-1239) with relapse and subsequently death in one patient who had high risk AML with 3 different inductions prior to SCT. . At 1 year for 4 evaluable patients IgG were \u3e400 mg/dl and CD4 \u3e 350 cells/ul. Conclusions: Cy2Bor3 post PB Haplo-SCT was well tolerated. Although small number of patients and limited but encouraging results so far. The trial is ongoing

The Association between Mediated Deprivation and Ovarian Cancer Survival among African American Women

BACKGROUND: Deprivation indices are often used to adjust for socio-economic disparities in health studies. Their role has been partially evaluated for certain population-level cancer outcomes, but examination of their role in ovarian cancer is limited. In this study, we evaluated a range of well-recognized deprivation indices in relation to cancer survival in a cohort of self-identified Black women diagnosed with ovarian cancer. This study aimed to determine if clinical or diagnostic characteristics lie on a mediating pathway between socioeconomic status (SES) and deprivation and ovarian cancer survival in a minority population that experiences worse survival from ovarian cancer. METHODS: We used mediation analysis to look at the direct and indirect causal effects of deprivation indices with main mediators of the SEER stage at diagnosis and residual disease. The analysis employed Bayesian structural equation models with variable selection. We applied a joint Bayesian structural model for the mediator, including a Weibull mixed model for the vital outcome with deprivation as exposure. We selected modifiers via a Monte Carlo model selection procedure. RESULTS: The results suggest that high SES-related indices, such as Yost, Kolak urbanicity (URB), mobility (MOB) and SES dimensions, and concentrated disadvantage index (CDI), all have a significant impact on improved survival. In contrast, area deprivation index (ADI)/Singh, and area level poverty (POV) did not have a major impact. In some cases, the indirect effects have very wide credible intervals, so the total effect is not well estimated despite the estimation of the direct effect. CONCLUSIONS: First, it is clear that commonly used indices such as Yost, or CDI both significantly impact the survival experience of Black women diagnosed with epithelial ovarian cancer. In addition, the Kolak dimension indices (URB, MOB, mixed immigrant: MICA and SES) also demonstrate a significant association, depending on the mediator. Mediation effects differ according to the mediator chosen

Emergent Semiclassical Time in Quantum Gravity. Full Geometrodynamics and Minisuperspace Examples

I apply the preceding paper's semiclassical treatment to geometrodynamics. The analogy between the two papers is quite useful at the level of the quadratic constraints, while I document the differences between the two due to the underlying differences in their linear constraints. I provide a specific minisuperspace example for my emergent semiclassical time scheme and compare it with the hidden York time scheme. Overall, interesting connections are shown between Newtonian, Leibniz--Mach--Barbour, WKB and cosmic times, while the Euler and York hidden dilational times are argued to be somewhat different from these.Comment: References Update

Diet and Survival in Black Women With Epithelial Ovarian Cancer

Ovarian cancer survival among Black women is the lowest across all racial and ethnic groups. Poor dietary quality also disproportionately affects Black populations, but its association with ovarian cancer survival in this population remains largely unknown.To examine associations between dietary patterns and survival among Black women diagnosed with epithelial ovarian cancer (EOC).This prospective cohort study was conducted among self-identified Black women aged 20 to 79 years newly diagnosed with histologically confirmed EOC in the African American Cancer Epidemiology Study (AACES) between December 2010 and December 2015, with follow-up until October 2022. AACES is a population-based study of ovarian cancer risk and survival among Black women in 11 US regions. Data were analyzed from March 2023 to June 2024.Dietary patterns were assessed by the Healthy Eating Index-2020 (HEI-2020) and Alternative Healthy Eating Index-2010 (AHEI-2010), with scores calculated based on dietary intake in the year prior to diagnosis and collected via the validated Block 2005 Food Frequency Questionnaire. Higher scores indicate better dietary quality.Hazard ratios (HRs) and 95grade serous ovarian cancer (HGSOC).Among 483 Black women with EOC (mean [SD] age, 58.1 [10.5] years), 310 deaths were recorded during a median (IQR) follow-up of 4.3 (2.0-8.2) years. No association of dietary patterns with mortality was found among women with EOC overall. However, among 325 women with HGSOC, better adherence to HEI-2020 was associated with decreased mortality in later quartiles compared with the first quartile (HR, 0.63; 95 0.44-0.92 for quartile 2; HR, 0.67; 95 0.46-0.97 for quartile 3; HR, 0.63; 95 0.44-0.91 for quartile 4 ). Similar results were observed with AHEI-2010 among women with HGSOC for the second (HR, 0.62; 95 0.43-0.89) and fourth (HR, 0.67; 95 0.45-0.98) quartiles compared with quartile 1.In this study, women with moderate and high prediagnosis dietary quality had significantly lower mortality rates from HGSOC compared with women with the lowest prediagnosis dietary quality. These findings suggest that even moderate adherence to dietary guidelines prior to diagnosis may be associated with improved survival among Black women with HGSOC, the most lethal form of ovarian cancer

Triangleland. I. Classical dynamics with exchange of relative angular momentum

In Euclidean relational particle mechanics, only relative times, relative angles and relative separations are meaningful. Barbour--Bertotti (1982) theory is of this form and can be viewed as a recovery of (a portion of) Newtonian mechanics from relational premises. This is of interest in the absolute versus relative motion debate and also shares a number of features with the geometrodynamical formulation of general relativity, making it suitable for some modelling of the problem of time in quantum gravity. I also study similarity relational particle mechanics (`dynamics of pure shape'), in which only relative times, relative angles and {\sl ratios of} relative separations are meaningful. This I consider firstly as it is simpler, particularly in 1 and 2 d, for which the configuration space geometry turns out to be well-known, e.g. S^2 for the `triangleland' (3-particle) case that I consider in detail. Secondly, the similarity model occurs as a sub-model within the Euclidean model: that admits a shape--scale split. For harmonic oscillator like potentials, similarity triangleland model turns out to have the same mathematics as a family of rigid rotor problems, while the Euclidean case turns out to have parallels with the Kepler--Coulomb problem in spherical and parabolic coordinates. Previous work on relational mechanics covered cases where the constituent subsystems do not exchange relative angular momentum, which is a simplifying (but in some ways undesirable) feature paralleling centrality in ordinary mechanics. In this paper I lift this restriction. In each case I reduce the relational problem to a standard one, thus obtain various exact, asymptotic and numerical solutions, and then recast these into the original mechanical variables for physical interpretation.Comment: Journal Reference added, minor updates to References and Figure

Clinical Study Prenatal Detection of Congenital Heart Diseases: One-Year Survey Performing a Screening Protocol in a Single Reference Center in Brazil

Objective. To describe the experience of a tertiary center in Brazil to which patients are referred whose fetuses are at increased risk for congenital heart diseases (CHDs). Methods. This was a cross-sectional observational study. The data was collected prospectively, during the year 2012, through a screening protocol of the fetal heart adapted from the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) guideline. We performed a fetal echocardiogram screening for all pregnant women who were referred to the fetal cardiology outpatient obstetrics clinic of a university hospital. The exams were classified as normal or abnormal. The cases considered abnormal were undergone to a postnatal echocardiogram. We categorized the abnormal fetal heart according to severity in "complex, " "significant, " "minor, " and "others. " Results. We performed 271 fetal heart screening. The incidence of abnormal screenings was 9.96% (27 fetuses). The structural CHD when categorized due to severity showed 48.1% ( = 13) of "complex" cases, 18.5% ( = 5) "significant" cases, and 7.4% ( = 2) "minor" cases. The most common referral reason was by maternal causes (67%) followed by fetal causes (33%). The main referral indication was maternal metabolic disease (30%), but there was just one fetus with CHD in such cases (1.2%). CHDs were found in 19/29 fetuses with suspicion of some cardiac abnormality by obstetrician (65.5%). Conclusion. We observed a high rate of CHD in our population. We also found that there was higher incidence of complex cases