What to be implemented at the early stage of a large-scale project

This paper addresses the importance of the actions to be taken before the project planning phases begin. The approach taken stems from the production planning paradigm, with emphasis on the product, rather than on the process. It is argued that a complete part list or product breakdown structure (PBS) is the absolute prerequisite for the design of a successful work breakdown structure (WBS) for a project. This process requires the definition of the design and configuration disciplines during the engineering phase. These critical issues of concurrent engineering and product development are also emphasized in the paper. The WBS is, in turn, needed to establish a suitable organizational breakdown structure (OBS or organigram) for the project. Finally, the assembly sequence and the related assembly breakdown structure (ABS) of the end product is required before commencing the project planning phase, which provides the schedules, resource allocation, progress control, and the like for the project management. Detailed definition of the product enables the definition of the work packages within the WBS, which combined with the installation information provide the means to structure the layout for the project organization. The result of the entire process, that begins with the product definition phase and ends with the completion of the planning phase, is called the project management plan. The procedure described in the paper will be used to design the project management plan for the Large Hadron Collider (LHC), a ten-year "ordeal" commencing at the beginning of the 1995, at CER

Engineering data management: a tool for technical coordination

This paper studies the basic motivations behind Engineering Data Management (EDM) in a decade long Large Hadron Collider (LHC) project with at least another decades operational period at CERN. The main argument is that without strict managerial principles to control engineering work the exploitation of EDM becomes impossible. Structured and organized configuration management is the absolute prerequisite for an effective integration of design, manufacturing and installation work. EDM is seen to provide all collaborating parties of the project with a coherent and up-to-date view of the product specifications together with other relevant information, such as products change log, responsibilities and status indicators during the products whole life-cycle. It is argued that by combining simple and commonly accepted managerial principles with an advanced EDM system the outcome supports the main phases of products evolution, i.e. design, assembly, operation and maintenance. The paper outlines the main tasks of the configuration management and the fundamental requirements of EDM in order to meet LHC-projects complexity, stringent budget, high quality and tight schedule constraints set by the CERN Council. Keywords: configuration management, new product development, project management, concurrent engineering, engineering data managemen

Phase III Clinical Trials in First-Line Follicular Lymphoma: A Review of Their Design and Interpretation

Follicular lymphoma (FL) is one of the most common subtypes of non-Hodgkin lymphoma worldwide. Improved survival outcomes with rituximab-based therapy in clinical trials led to the establishment of rituximab-based immunochemotherapy as standard of care for first-line (1L) treatment of FL. In the GALLIUM trial, obinutuzumab-based immunochemotherapy demonstrated improved progression-free survival (PFS), prolonged time-to-next antilymphoma treatment (TTNT) and comparable overall survival (OS) compared with rituximab-based immunochemotherapy as 1L treatment for FL. Using GALLIUM as an example, this article aims to explain how improved outcomes in 1L treatment of FL have changed the landscape for the design and interpretation of future trials. As approved therapies for 1L FL already achieve good responses, it is becoming more difficult to design trials that demonstrate further treatment benefits with the currently accepted primary endpoints. New endpoints are needed to reflect the long remission times, low relapse rates, and impact of subsequent therapies in FL. PFS is used as a primary efficacy endpoint in registrational clinical trials for indolent malignancies like FL, where improvement in OS is not always observed due to the large number of patients and long study duration required to demonstrate a clear survival benefit. However, there are limitations to using PFS as the primary endpoint. Other potential endpoints, including TTNT, progression of disease within 2 years, response rate, and minimal residual disease status are explored

Phytoplankton surveys in the Arctic Fram Strait demonstrate the tiny eukaryotic alga Micromonas and other picoprasinophytes contribute to deep sea export

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Bachy, C., Sudek, L., Choi, C. J., Eckmann, C. A., Nöthig, E.-M., Metfies, K., & Worden, A. Z. Phytoplankton surveys in the Arctic Fram Strait demonstrate the tiny eukaryotic alga Micromonas and other picoprasinophytes contribute to deep sea export. Microorganisms, 10(5), (2022): 961, https://doi.org/10.3390/microorganisms10050961.Critical questions exist regarding the abundance and, especially, the export of picophytoplankton (≤2 µm diameter) in the Arctic. These organisms can dominate chlorophyll concentrations in Arctic regions, which are subject to rapid change. The picoeukaryotic prasinophyte Micromonas grows in polar environments and appears to constitute a large, but variable, proportion of the phytoplankton in these waters. Here, we analyze 81 samples from the upper 100 m of the water column from the Fram Strait collected over multiple years (2009–2015). We also analyze sediment trap samples to examine picophytoplankton contributions to export, using both 18S rRNA gene qPCR and V1-V2 16S rRNA Illumina amplicon sequencing to assess the Micromonas abundance within the broader diversity of photosynthetic eukaryotes based on the phylogenetic placement of plastid-derived 16S amplicons. The material sequenced from the sediment traps in July and September 2010 showed that 11.2 ± 12.4% of plastid-derived amplicons are from picoplanktonic prasinophyte algae and other green lineage (Viridiplantae) members. In the traps, Micromonas dominated (83.6 ± 21.3%) in terms of the overall relative abundance of Viridiplantae amplicons, specifically the species Micromonas polaris. Temporal variations in Micromonas abundances quantified by qPCR were also observed, with higher abundances in the late-July traps and deeper traps. In the photic zone samples, four prasinophyte classes were detected in the amplicon data, with Micromonas again being the dominant prasinophyte, based on the relative abundance (89.4 ± 8.0%), but with two species (M. polaris and M. commoda-like) present. The quantitative PCR assessments showed that the photic zone samples with higher Micromonas abundances (>1000 gene copies per mL) had significantly lower standing stocks of phosphate and nitrate, and a shallower average depth (20 m) than those with fewer Micromonas. This study shows that despite their size, prasinophyte picophytoplankton are exported to the deep sea, and that Micromonas is particularly important within this size fraction in Arctic marine ecosystems.This research was supported by funding from the National Science Foundation (NSF) DEB-1639033, Gordon and Betty Moore Foundation Marine Investigator Award grant 3788, and fellowships from the Radcliffe Institute for Advanced Research at Harvard University and the Hanse-Wissenschaftskolleg for Marine and Climate Science, awarded to A.Z.W. Contribution to HGF POF-IV 6.1, 6.3, and 6.4

Controversies in the Treatment of Peripheral T-cell Lymphoma.

Peripheral T-cell lymphomas are a heterogeneous group of rare diseases with an aggressive behavior and dismal prognosis. Their classification is complex and still evolving, and several biomolecular markers now help refine the prognosis of specific disease entities, although still have limited impact in tailoring the treatment. First-line treatment strategies can cure only a minority of patients and relapsed-refractory disease still represents the major cause of failure. Frontline autologous transplantation may have an impact in the consolidation of response; however, its role is still questioned as far as complete responses obtained after induction chemotherapy are concerned. Newer drugs are now being evaluated in clinical trials, but effective salvage strategies for those who experience treatment failures are lacking. Here we review and discuss the most controversial aspects of diagnosis and treatment of peripheral T-cell lymphomas

Meningitis Serogroup W135 Outbreak, Burkina Faso, 2002

In 2002, the largest epidemic of Neisseria meningitidis serogroup W135 occurred in Burkina Faso. The highest attack rate was in children <5 years of age. We describe cases from 1 district and evaluate the performance of the Pastorex test, which had good sensitivity (84%) and specificity (89%) compared with culture or PCR