We present a rapid method for the exact calculation of the cumulative distribution function of the maximum of multinomially distributed random variables. The method runs in time O(mn), where m is the desired maximum and n is the number of variables. We apply the method to the analysis of two situations in which an apparent clustering of cases of a disease in some locality has raised epidemiological concerns, and these concerns have been discussed in the recent literature. We conclude that one of these clusters may be explained on purely random grounds, namely the leukemia cluster in Niles, IL, in 1956-1960; whereas the other, a leukemia cluster in Fallon, NV, in 1999-2001, may not.
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http://dx.doi.org/10.1073/pnas.0704691104 | DOI Listing |
Micromachines (Basel)
January 2025
Center of Competence at Mechatronics and Clean Technologies-MIRACle, "Acad. G. Bontchev" Str. 4, 1113 Sofia, Bulgaria.
Chronic lymphocytic leukemia (CLL), the most common type of leukemia, remains incurable with conventional therapy. Despite advances in therapies targeting Bruton's tyrosine kinase and anti-apoptotic protein BCL-2, little is known about their effect on red blood cell (RBC) aggregation in blood flow. In this study, we applied a microfluidic device and a newly developed Software Image Flow Analysis to assess the extent of RBC aggregation in CLL patients and to elucidate the hemorheological effects of the commonly applied therapeutics Obinutuzumab/Venetoclax and Ibrutinib.
View Article and Find Full Text PDFBlood
January 2025
Division of Immunology and Allergy, Children's Hospital of Philadelphia; Department of Pediatrics, Perelman School of Medicine; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Leukopoiesis is lethally arrested in mice lacking the master transcriptional regulator PU.1. Depending on the animal model, subtotal PU.
View Article and Find Full Text PDFHematol Rep
January 2025
Department of 1st Internal Medicine, Medical School, University of Pécs, Ifjúság Str. 13, 7624 Pécs, Hungary.
T-cell prolymphocytic leukemia (T-PLL) is a rare mature T-cell lymphoma that is usually associated with poor prognosis and short overall survival. We present a case of a 61-year-old woman presenting with T-PLL and the leukemic cells harboring (-breakpoint cluster region; -ABL protooncogene 1) fusion transcripts as the result of a variant of t(9;22)(q34;q11) called Philadelphia translocation: t(9;22;18)(q34;q11;q21). Sequencing revealed a rare transcript with an exon 6 breakpoint corresponding to e6a2 transcripts, which has thus far been reported in only 26 cases of leukemias.
View Article and Find Full Text PDFJCI Insight
January 2025
Centre for Cancer Research, Hudson Institute of Medical Research, and.
Pediatric high-grade gliomas (pHGGs) are the most aggressive brain tumors in children, necessitating innovative therapies to improve outcomes. Unlike adult gliomas, recent research reveals that childhood gliomas have distinct biological features, requiring specific treatment strategies. Here, we focused on deciphering unique genetic dependencies specific to childhood gliomas.
View Article and Find Full Text PDFPharm Stat
January 2025
Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Clinical trials (CTs) often suffer from small sample sizes due to limited budgets and patient enrollment challenges. Using historical data for the CT data analysis may boost statistical power and reduce the required sample size. Existing methods on borrowing information from historical data with right-censored outcomes did not consider matching between historical data and CT data to reduce the heterogeneity.
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