A glycosylated recombinant human granulocyte colony stimulating factor produced in a novel protein production system (AVI-014) in healthy subjects: a first-in human, single dose, controlled study

BACKGROUND: AVI-014 is an egg white-derived, recombinant, human granulocyte colony-stimulating factor (G-CSF). This healthy volunteer study is the first human investigation of AVI-014. METHODS: 24 male and female subjects received a single subcutaneous injection of AVI-014 at 4 or 8 mcg/kg. 16 control subjects received 4 or 8 mcg/kg of filgrastim (Neupogen, Amgen) in a partially blinded, parallel fashion. RESULTS: The Geometric Mean Ratio (GMR) (90% CI) of 4 mcg/kg AVI-014/filgrastim AUC(0-72 hr) was 1.00 (0.76, 1.31) and Cmax was 0.86 (0.66, 1.13). At the 8 mcg/kg dose, the AUC(0-72) GMR was 0.89 (0.69, 1.14) and Cmax was 0.76 (0.58, 0.98). A priori pharmacokinetic bioequivalence was defined as the 90% CI of the GMR bounded by 0.8-1.25. Both the white blood cell and absolute neutrophil count area under the % increase curve AUC(0-9 days) and Cmax (maximal % increase from baseline)GMR at 4 and 8 mcg/kg fell within the 0.5-2.0 a priori bound set for pharmacodynamic bioequivalence. The CD 34+ % increase curve AUC(0-9 days) and Cmax GMR for both doses was approximately 1, but 90% confidence intervals were large due to inherent variance, and this measure did not meet pharmacodynamic bioequivalence. AVI-014 demonstrated a side effect profile similar to that of filgrastim. CONCLUSION: AVI-014 has safety, pharmacokinetic, and pharmacodynamic properties comparable to filgrastim at an equal dose in healthy volunteers. These findings support further investigation in AVI-014

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe

A Case of Chemotherapy-Refractory “THRLBCL like Transformation of NLPHL” Successfully Treated with Lenalidomide

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a subtype of nonclassical Hodgkin lymphoma (HL). It resembles non-Hodgkin lymphoma (NHL), by expressing classic B cell markers such as CD20 and CD79a however lacks definitive HL markers (such as CD15 and CD30). T cell histiocyte-rich large B cell lymphoma (THRLBCL), on the other hand, is a distinct entity classified under NHL and considered a variant of diffuse large B cell lymphoma (DLBCL). NLPHL can look morphologically and immunologically similar to THRLBCL and often poses a diagnostic challenge. Neoplastic cells in both NLPHL and THRLBCL express B cell markers and are typically scattered in a background of reactive cells. The two major differences are the background cell type and the morphologic pattern. Despite having a phenotypic resemblance, they have distinct biologic behavior and clinical course. NLPHL typically has an indolent course, and THRLBCL has an aggressive course. Hence, differentiating these two entities is critical not only for prognosis but for treatment purposes. Of note, NLPHL has a small risk of transformation to an aggressive lymphoma such as THRLBCL