GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia.

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P \u3c .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P \u3c .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors. © 2019 American Society of Hematology. All rights reserved

Casimir energy and black hole pair creation in Schwarzschild-de Sitter spacetime

Following the subtraction procedure for manifolds with boundaries, we calculate by variational methods, the Schwarzschild-de Sitter and the de Sitter space energy difference. By computing the one loop approximation for TT tensors we discover the existence of an unstable mode even for the non-degenerate case. This result seems to be in agreement with the sub-maximal black hole pair creation of Bousso-Hawking. The instability can be eliminated by the boundary reduction method. Implications on a foam-like space are discussed.Comment: 19 pages,RevTeX with package epsf and four eps figures. Added other references. Accepted for publication in Classical and Quantum Gravit

Classical and Thermodynamic Stability of Black Branes

It is argued that many non-extremal black branes exhibit a classical Gregory-Laflamme instability if, and only if, they are locally thermodynamically unstable. For some black branes, the Gregory-Laflamme instability must therefore disappear near extremality. For the black $p$-branes of the type II supergravity theories, the Gregory-Laflamme instability disappears near extremality for $p=1,2,4$ but persists all the way down to extremality for $p=5,6$ (the black D3-brane is not covered by the analysis of this paper). This implies that the instability also vanishes for the near-extremal black M2 and M5-brane solutions.Comment: 21 pages, LaTeX. v2: Various points clarified, typos corrected and reference adde

Some Aspects of Virtual Black Holes

In this paper we shall consistently third quantize modified gravity. Then we shall analyse certain aspects of virtual black holes in this third quantized modified gravity. We will see how a statistical mechanical origin for the Bekenstein-Hawking entropy naturally arises in this model. Furthermore, in this model the area and thus the entropy of a real macroscopic black hole is quantized. Virtual black holes cause loss of quantum coherence and this gives an intrinsic entropy to all physical systems which can be used to define a direction of time and hence provide a solution to the problem of time.Comment: 11 pages, 0 figures, accepted for publication in JET

Avian haemosporidian diversity on Sardinia: a first general assessment for the Insular Mediterranean

The Western Palearctic is one of the most investigated regions for avian haemosporidian parasites (Haemoproteus, Plasmodium and Leucocytozoon), yet geographic gaps in our regional knowledge remain. Here, we report the first haemosporidian screening of the breeding birds from Sardinia (the second-largest Mediterranean Island and a biodiversity hotspot), and the first for the insular Mediterranean in general. We examined the occurrence of haemosporidians by amplifying their mtDNA cytb gene in 217 breeding birds, belonging to 32 species. The total prevalence of infected birds was 55.3%, and of the 116 haplotypes recovered, 84 were novel. Despite the high number of novel lineages, phylogenetic analysis did not highlight Sardinia-specific clades; instead, some Sardinian lineages were more closely related to lineages previously recovered from continental Europe. Host-parasite network analysis indicated a specialized host-parasite community. Binomial generalized linear models (GLMs), performed at the community level, suggested an elevational effect on haemosporidian occurrence probability (negative for Haemoproteus; positive for Leucocytozoon) likely due to differences in the abundance of insect vectors at different elevations. Furthermore, a GLM revealed that sedentary birds showed a higher probability of being infected by novel haplotypes and long-distance migrants showed a lower probability of novel haplotype infection. We hypothesize that the high diversity of haemosporidians is linked to the isolation of breeding bird populations on Sardinia. This study adds to the growing knowledge on haemosporidians lineage diversity and distribution in insular environments and presents new insights on potential host-parasite associations

Current European Labyrinthula zosterae Are Not Virulent and Modulate Seagrass (Zostera marina) Defense Gene Expression

Pro- and eukaryotic microbes associated with multi-cellular organisms are receiving increasing attention as a driving factor in ecosystems. Endophytes in plants can change host performance by altering nutrient uptake, secondary metabolite production or defense mechanisms. Recent studies detected widespread prevalence of Labyrinthula zosterae in European Zostera marina meadows, a protist that allegedly caused a massive amphi-Atlantic seagrass die-off event in the 1930's, while showing only limited virulence today. As a limiting factor for pathogenicity, we investigated genotype×genotype interactions of host and pathogen from different regions (10–100 km-scale) through reciprocal infection. Although the endophyte rapidly infected Z. marina, we found little evidence that Z. marina was negatively impacted by L. zosterae. Instead Z. marina showed enhanced leaf growth and kept endophyte abundance low. Moreover, we found almost no interaction of protist×eelgrass-origin on different parameters of L. zosterae virulence/Z. marina performance, and also no increase in mortality after experimental infection. In a target gene approach, we identified a significant down-regulation in the expression of 6/11 genes from the defense cascade of Z. marina after real-time quantitative PCR, revealing strong immune modulation of the host's defense by a potential parasite for the first time in a marine plant. Nevertheless, one gene involved in phenol synthesis was strongly up-regulated, indicating that Z. marina plants were probably able to control the level of infection. There was no change in expression in a general stress indicator gene (HSP70). Mean L. zosterae abundances decreased below 10% after 16 days of experimental runtime. We conclude that under non-stress conditions L. zosterae infection in the study region is not associated with substantial virulence

IPNA clinical practice recommendations on care of pediatric patients with pre-existing kidney disease during seasonal outbreak of COVID-19

The coronavirus disease 2019 (COVID-19) pandemic, instigated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has profoundly impacted healthcare infrastructures around the globe. While children are usually asymptomatic or have mild symptoms, children with pre-existing kidney conditions require specialized attention. This pivotal report, championed by the International Pediatric Nephrology Association (IPNA), delivers precise and actionable recommendations tailored for pediatric patients with kidney ailments in this pandemic landscape. Central to our findings are rigorous infection control protocols. These are particularly stringent in high-risk zones, emphasizing telehealth's indispensable role, the significance of curtailing in-person consultations, and the imperative of following rigorous guidelines in regions with heightened COVID-19 prevalence. Additionally, the report delves into vaccination approaches for children with kidney issues, highlighting that the choice of vaccine is often governed by regional accessibility and policy frameworks, rather than a universal preference. A notable observation is the potential correlation between COVID-19 vaccines and specific kidney disorders. However, establishing a direct causal link remains elusive. In summary, our research accentuates the critical need for specialized pediatric kidney care during global health crises and reaffirms the continuous research imperative, especially regarding vaccination ramifications

Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide

Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P =.002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P <.001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P =.01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P =.01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival