Heavy Higgs production and decay via e+e−→Z0H0→bbˉZ0Z0e^+e^-\to Z^0 H^0 \to b\bar bZ^0Z^0 and irreducible backgrounds at Next Linear Colliders

The complete matrix element for e^+e^-\ar b\bar bZ^0Z^0 has been computed at tree--level and applied to $Z^0H^0$--production followed by Z^0\ar b\bar b and H^0\ar Z^0Z^0, including all the irreducible background, at Next Linear Colliders. We find that, assuming flavour identification of the $Z^0$--decay products, this channel, together with e^+e^-\ar b\bar bW^+W^- in which Z^0H^0\ar (b\bar b)(W^+W^-), can be important for the study of the parameters of the Standard Model Higgs boson over the heavy mass range 2M_{Z^0}\Ord M_{H^0}\Ord 2{m_t}.Comment: 24 pages, LaTeX (uses Feynman), 7 figures (.ps files or hardcopies of figs.2-7 available upon request

Acromegaly and gigantism in the medical literature. Case descriptions in the era before and the early years after the initial publication of Pierre Marie (1886)

In 1886 Pierre Marie used the term “acromegaly” for the first time and gave a full description of the characteristic clinical picture. However several others had already given clear clinical descriptions before him and sometimes had given the disease other names. After 1886, it gradually became clear that pituitary enlargement (caused by a pituitary adenoma) was the cause and not the consequence of acromegaly, as initially thought. Pituitary adenomas could be found in the great majority of cases. It also became clear that acromegaly and gigantism were the same disease but occurring at different stages of life and not different diseases as initially thought. At the end of the 19th and beginning of the 20th century most information was derived from case descriptions and post-mortem examinations of patients with acromegaly or (famous) patients with gigantism. The stage was set for further research into the pathogenesis, diagnosis and therapy of acromegaly and gigantism

Immunogenomic identification and characterization of granulocytic myeloid-derived suppressor cells in multiple myeloma

Granulocytic myeloid-derived suppressor cells (G-MDSCs) promote tumor growth and immunosuppression in multiple myeloma (MM). However, their phenotype is not well established for accurate monitoring or clinical translation. We aimed to provide the phenotypic profile of G-MDSCs based on their prognostic significance in MM, immunosuppressive potential, and molecular program. The preestablished phenotype of G-MDSCs was evaluated in bone marrow samples from controls and MM patients using multidimensional flow cytometry; surprisingly, we found that CD11b1CD142CD151CD331HLADR2 cells overlapped with common eosinophils and neutrophils, which were not expanded in MM patients. Therefore, we relied on automated clustering to unbiasedly identify all granulocytic subsets in the tumor microenvironment: basophils, eosinophils, and immature, intermediate, and mature neutrophils. In a series of 267 newly diagnosed MM patients (GEM2012MENOS65 trial), only the frequency of mature neutrophils at diagnosis was significantly associated with patient outcome, and a high mature neutrophil/T-cell ratio resulted in inferior progression-free survival (P <.001). Upon fluorescence-activated cell sorting of each neutrophil subset, T-cell proliferation decreased in the presence of mature neutrophils (0.5-fold; P 5.016), and the cytotoxic potential of T cells engaged by a BCMA3CD3-bispecific antibody increased notably with the depletion of mature neutrophils (fourfold; P 5.0007). Most interestingly, RNA sequencing of the 3 subsets revealed that G-MDSC-related genes were specifically upregulated in mature neutrophils from MM patients vs controls because of differential chromatin accessibility. Taken together, our results establish a correlation between the clinical significance, immunosuppressive potential, and transcriptional network of well-defined neutrophil subsets, providing for the first time a set of optimal markers (CD11b/CD13/CD16) for accurate monitoring of G-MDSCs in MM