Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide Conditioning and Autologous Stem Cell Transplantation for Lymphoma: Comparison of a Multicenter Phase II Study and CIBMTR Outcomes.

Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended due to high early treatment-related mortality (TRM) in patients > 65 years. BuCyE outcomes were compared with contemporaneous recipients of carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for International Blood and Marrow Transplant Research. Two hundred seven subjects with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America, and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65 years (n = 17), and patients ≤ 65 years (n = 186) were 4.5%, 23.5%, and 2.7%, respectively. The estimated rates of 2-year progression-free survival (PFS) were 33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n = 63), mantle cell lymphoma (MCL; n = 29), and follicular lymphoma (FL; n = 23), respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there were no differences in outcomes for NHL. Patients with HL had lower rates of 2-year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52% to 66%), with no differences in TRM or OS. BuCyE provided adequate disease control and safety in B cell NHL patients ≤ 65 years but produced worse PFS in HL patients when compared with BEAM.

DEK oncogene expression during normal hematopoiesis and in Acute Myeloid Leukemia (AML)

DEK is important in regulating cellular processes including proliferation, differentiation and maintenance of stem cell phenotype. The translocation t(6;9) in Acute Myeloid Leukemia (AML), which fuses DEK with NUP214, confers a poor prognosis and a higher risk of relapse. The over-expression of DEK in AML has been reported, but different studies have shown diminished levels in pediatric and promyelocytic leukemias. This study has characterized DEK expression, in silico, using a large multi-center cohort of leukemic and normal control cases. Overall, DEK was under-expressed in AML compared to normal bone marrow (NBM). Studying specific subtypes of AML confirmed either no significant change or a significant reduction in DEK expression compared to NBM. Importantly, the similarity of DEK expression between AML and NBM was confirmed using immunohistochemistry analysis of tissue mircorarrays. In addition, stratification of AML patients based on median DEK expression levels indicated that DEK showed no effect on the overall survival of patients. DEK expression during normal hematopoiesis did reveal a relationship with specific cell types implicating a distinct function during myeloid differentiation. Whilst DEK may play a potential role in hematopoiesis, it remains to be established whether it is important for leukemagenesis, except when involved in the t(6;9) translocation.

Chaotropic and hydrophobic stress mechanisms of antifungal substances

Growth and metabolism of fungi can be curtailed by chaotropic solutes and hydrophobic substances, both of which can weaken or inhibit non-covalent interactions within and between macromolecular systems. Here we explore the potential to utilize the fungistatic and fungicidal activities of such stressors as the basis for commercial formulations. A method was developed for the quantification of chaotropicity, which can be used for chemically diverse substances, in order elucidate roles of chaotropicity and hydrophobicity in microbial ecology (both of which are sufficiently potent to limit the Earth’s microbial biosphere). A large number of naturally occurring substances act as chaotropic or hydrophobic stressors including aliphatic alcohols, salts such as MgCl2, aromatics such as phenol, and hydrocarbons such as hexane and octene. We suggest that these stress parameters provide the (hitherto unidentified) modes-of-action for some extant antifungal products. The findings are discussed in relation to the development of a new generation of antifungals.

Modelling Damage in Thin-Walled Structures [Keynote speaker]

A high-fidelity composite damage model is presented and applied to predict low-velocity impact damage, compression after impact (CAI) strength and crushing of thin-walled composite structures. The simulated results correlated well with experimental testing in terms of overall force-displacement response, damage morphologies and energy dissipation. The predictive power of this model makes it suitable for use as part of a virtual testing methodology, reducing the reliance on physical testing.  

A importância dos processos físicos no controlo da eutrofização em estuários

Muitos dos problemas tróficos existentes nos estuários e zonas costeiras têm origem no excesso de nutrientes, em particular Azoto (N) e Fósforo (P), resultante do sucessivo enriquecimento dos rios durante o seu percurso até ao mar e também de descargas directas nestes sistemas. Nixon (1995) definiu eutrofização como o aumento da quantidade de matéria orgânica disponível na massa de água. Esta é uma definição assumida neste estudo, considerando que a eutrofização é o primeiro, de uma sequência de fenómenos resultantes do sobre-enriquecimento de nutrientes, que inclui a alteração de espécies dominantes e o aumento dos níveis de turbidez da água.

A methodology to estimate the residence time of estuaries

The residence time has long been used as a classification parameter for estuaries and other semi- enclosed water bodies. It aims to quantify the time water remains inside the estuary, being used as an indicator both for pollution assessment and for ecological processes. Estuaries with a short residence time will export nutrients from upstream sources more rapidly then estuaries with longer residence time. On the other hand the residence time determines if micro-algae can stay long enough to generate a bloom. As a consequence, estuaries with very short residence time are expected to have much lower algae blooms, then estuaries with longer residence time. In addition, estuaries with residence times shorter than the doubling time of algae cells will inhibit formation of algae blooms (EPA, 2001). The residence time is also an important issue for processes taking place in the sediment. The fluxes of particulate matter and associated adsorbed species from the water column to the sediment depends of the particle’s vertical velocity, water depth and residence time. This is particularly important for the fine fractions with lower sinking velocities. The question is how to compute the residence time and how does it depend on the computation method adopted.

Development of an integrated system for coastal waters

This paper describes some of the needs and problems associated to assessment of coastal and estuarine problems (sediment transport and eutrophication). The development of an integrated system including EO data, local measurements with special emphasis on modeling tools, is presented as a solution for studying and helping decision making on the subject. Two pilot sites for the implementation and the present development status of the integrated system are depicted. This framework was already presented in a recent AO specific for Portugal, which is still under evaluation.

Algorithmen zur automatischen 4dimensionalen Flugbahnführung unter Berücksichtigung der momentanen Windsituation

Für das digitale Flugführungssystem des Versuchsflugzeugs HFB 320 wurde am Institut für Flugführung der DFVLR in Braunschweig eine Betriebsart zum automatischen zeitgenauen Fliegen im Flughafen-Nahbereich entwickelt und im Flugversuch erprobt. Der Bericht enthält die Beschreibung der eingesetzten Algorithmen zur Berechnung 4-dimensionaler Flugbahnen unter Berücksichtigung der momentanen Windsituation. Es werden verschiedene Verfahren zur Messung, Filterung und Vorhersage des Windvektors entwickelt und an Hand von Flugversuchsergebnissen diskutiert.