Evaluating cost taxonomies for information systems management

The consideration of costs, benefits and risks underpin many Information System (IS) evaluation decisions. Yet, vendors and project-champions alike tend to identify and focus much of their effort on the benefits achievable from the adoption of new technology, as it is often not in the interest of key stakeholders to spend too much time considering the wider cost and risk implications of enterprise-wide technology adoptions. In identifying a void in the literature, the authors of the paper present a critical analysis of IS-cost taxonomies. In doing so, the authors establish that such cost taxonomies tend to be esoteric and difficult to operationalize, as they lack specifics in detail. Therefore, in developing a deeper understanding of IS-related costs, the authors position the need to identify, control and reduce IS-related costs within the information systems evaluation domain, through culminating and then synthesizing the literature into a frame of reference that supports the evaluation of information systems through a deeper understanding of IS-cost taxonomies. The paper then concludes by emphasizing that the total costs associated with IS-adoption can only be determined after having considered the multi-faceted dimensions of information system investments

A First Global Oceanic Compilation of Observational Dissolved Aluminum Data With Regional Statistical Data Treatment

Large national and international observational efforts over recent decades have provided extensive and invaluable datasets of a range of ocean variables. Compiled large datasets, structured, or unstructured, are a powerful tool that allow scientists to access and synthesize data collected over large spatial and temporal scales. The data treatment approaches for any element in the ocean could lead to new global perspectives of their distribution patterns and to a better understanding of large-scale oceanic processes and their impact on other biogeochemical cycles, which may not be evident otherwise. Ocean chemistry Big Data analysis may not just be limited to distribution patterns, but may be used to assess how sampling efforts and analytical methodologies can be improved. Furthermore, a systematic global scale assessment of data is important to evaluate the gaps in knowledge and to provide avenues for future research. In this context, here we provide an extensive compilation of oceanic aluminum (Al) concentration data from global ocean basins, including data available in the GEOTRACES Intermediate Data product (Schlitzer et al., 2018), but also thus far unpublished data

Outcomes and toxicity of allogeneic hematopoietic cell transplantation in chronic myeloid leukemia patients previously treated with second-generation tyrosine kinase inhibitors : a prospective non-interventional study from the Chronic Malignancy Working Party of the EBMT

Allogeneic hematopoietic cell transplantation (allo-HCT) remains a treatment option for patients with chronic myeloid leukemia (CML) who fail to respond to tyrosine kinase inhibitors (TKIs). While imatinib seems to have no adverse impact on outcomes after transplant, little is known on the effects of prior use of second-generation TKI (2GTKI). We present the results of a prospective non-interventional study performed by the EBMT on 383 consecutive CML patients previously treated with dasatinib or nilotinib undergoing allo-HCT from 2009 to 2013. The median age was 45 years (18-68). Disease status at transplant was CP1 in 139 patients (38%), AP or >CP1 in 163 (45%), and BC in 59 (16%). The choice of 2GTKI was: 40% dasatinib, 17% nilotinib, and 43% a sequential treatment of dasatinib and nilotinib with or without bosutinib/ponatinib. With a median follow-up of 37 months (1-77), 8% of patients developed either primary or secondary graft failure, 34% acute and 60% chronic GvHD. There were no differences in post-transplant complications between the three different 2GTKI subgroups. Non-relapse mortality was 18% and 24% at 12 months and at 5 years, respectively. Relapse incidence was 36%, overall survival 56% and relapse-free survival 40% at 5 years. No differences in post-transplant outcomes were found between the three different 2GTKI subgroups. This prospective study demonstrates the feasibility of allo-HCT in patients previously treated with 2GTKI with a post-transplant complications rate comparable to that of TKI-naive or imatinib-treated patients.Peer reviewe

Evolutionary Reshaping of Fungal Mating Pathway Scaffold Proteins

Scaffold proteins play central roles in the function of many signaling pathways. Among the best-studied examples are the Ste5 and Far1 proteins of the yeast Saccharomyces cerevisiae. These proteins contain three conserved modules, the RING and PH domains, characteristic of some ubiquitin-ligating enzymes, and a vWA domain implicated in protein-protein interactions. In yeast, Ste5p regulates the mating pathway kinases while Far1p coordinates the cellular polarity machinery. Within the fungal lineage, the Basidiomycetes and the Pezizomycetes contain a single Far1-like protein, while several Saccharomycotina species, belonging to the CTG (Candida) clade, contain both a classic Far1-like protein and a Ste5-like protein that lacks the vWA domain. We analyzed the function of C. albicans Ste5p (Cst5p), a member of this class of structurally distinct Ste5 proteins. CST5 is essential for mating and still coordinates the mitogen-activated protein (MAP) kinase (MAPK) cascade elements in the absence of the vWA domain; Cst5p interacts with the MEK kinase (MEKK) C. albicans Ste11p (CaSte11p) and the MAPK Cek1 as well as with the MEK Hst7 in a vWA domain-independent manner. Cst5p can homodimerize, similar to Ste5p, but can also heterodimerize with Far1p, potentially forming heteromeric signaling scaffolds. We found direct binding between the MEKK CaSte11p and the MEK Hst7p that depends on a mobile acidic loop absent from S. cerevisiae Ste11p but related to the Ste7-binding region within the vWA domain of Ste5p. Thus, the fungal lineage has restructured specific scaffolding modules to coordinate the proteins required to direct the gene expression, polarity, and cell cycle regulation essential for mating

Measurable residual disease at myeloablative allogeneic transplantation in adults with acute lymphoblastic leukemia : a retrospective registry study on 2780 patients from the acute leukemia working party of the EBMT

Background: Assessment of measurable residual disease (MRD) is rapidly transforming the therapeutic and prognostic landscape of a wide range of hematological malignancies. Its prognostic value in acute lymphoblastic leukemia (ALL) has been established and MRD measured at the end of induction is increasingly used to guide further therapy. Although MRD detectable immediately before allogeneic hematopoietic cell transplantation (HCT) is known to be associated with poor outcomes, it is unclear if or to what extent this differs with different types of conditioning. Methods: In this retrospective registry study, we explored whether measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia is associated with different outcomes in recipients of myeloablative total body irradiation (TBI)-based versus chemotherapy-based conditioning. We analyzed outcomes of 2780 patients (median age 38 years, range 18-72) who underwent first HCT in complete remission between 2000 and 2017 using sibling or unrelated donors. Results: In 1816 of patients, no disease was detectable, and in 964 patients, MRD was positive. Conditioning was TBI-based in 2122 (76%) transplants. In the whole cohort MRD positivity was a significant independent factor for lower overall survival (OS) and leukemia-free survival (LFS), and for higher relapse incidence (RI), with respective hazard ratios (HR, 95% confidence intervals) of 1.19 (1.02-1.39), 1.26 (1.1-1.44), and 1.51 (1.26-1.8). TBI was associated with a higher OS, LFS, and lower RI with HR of 0.75 (0.62-0.90), 0.70 (0.60-0.82), and 0.60 (0.49-0.74), respectively. No significant interaction was found between MRD status and conditioning. When investigating the impact of MRD separately in the TBI and chemotherapy-based conditioning cohorts by multivariate analysis, we found MRD positivity to be associated with lower OS and LFS and higher RI in the TBI group, and with higher RI in the chemotherapy group. TBI-based conditioning was associated with improved outcomes in both MRD-negative and MRD-positive patients. Conclusions: In this large study, we confirmed that patients who are MRD-negative prior to HCT achieve superior outcomes. This is particularly apparent if TBI conditioning is used. All patients with ALL irrespective of MRD status benefit from TBI-based conditioning in the myeloablative setting.Peer reviewe

Complications of Autologous Stem Cell Transplantation in Multiple Myeloma : Results from the CALM Study

Background: The main goal of this post hoc analysis of the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study was to evaluate the rate of short- and long-term infectious and non-infectious complications occurring after ASCT in patients with multiple myeloma (MM). Methods: The analysis included all patients with MM from the CALM study who underwent >= 1 ASCT. The primary endpoint of the analysis was to determine the rate of infectious and non-infectious complications after ASCT and to compare them in three time periods: 0-100 days, 101 days-1 year, and >1 year after the first transplant. Results: The analysis included a total of 3552 patients followed up for a median of 56.7 months (range 0.4-108.1). Complication rates decreased with the time from ASCT with 24.85 cases per 100 patient-years from day 0 to 100 days after the transplant, andPeer reviewe

Deciphering the stem cell machinery as a basis for understanding the molecular mechanism underlying reprogramming

Stem cells provide fascinating prospects for biomedical applications by combining the ability to renew themselves and to differentiate into specialized cell types. Since the first isolation of embryonic stem (ES) cells about 30 years ago, there has been a series of groundbreaking discoveries that have the potential to revolutionize modern life science. For a long time, embryos or germ cell-derived cells were thought to be the only source of pluripotency—a dogma that has been challenged during the last decade. Several findings revealed that cell differentiation from (stem) cells to mature cells is not in fact an irreversible process. The molecular mechanism underlying cellular reprogramming is poorly understood thus far. Identifying how pluripotency maintenance takes place in ES cells can help us to understand how pluripotency induction is regulated. Here, we review recent advances in the field of stem cell regulation focusing on key transcription factors and their functional interplay with non-coding RNAs

The GEOTRACES Intermediate Data Product 2014

The GEOTRACES Intermediate Data Product 2014 (IDP2014) is the first publicly available data product of the international GEOTRACES programme, and contains data measured and quality controlled before the end of 2013. It consists of two parts: (1) a compilation of digital data for more than 200 trace elements and isotopes (TEIs) as well as classical hydrographic parameters, and (2) the eGEOTRACES Electronic Atlas providing a strongly inter-linked on-line atlas including more than 300 section plots and 90 animated 3D scenes. The IDP2014 covers the Atlantic, Arctic, and Indian oceans, exhibiting highest data density in the Atlantic. The TEI data in the IDP2014 are quality controlled by careful assessment of intercalibration results and multi-laboratory data comparisons at cross-over stations. The digital data are provided in several formats, including ASCII spreadsheet, Excel spreadsheet, netCDF, and Ocean Data View collection. In addition to the actual data values the IDP2014 also contains data quality flags and 1-? data error values where available. Quality flags and error values are useful for data filtering. Metadata about data originators, analytical methods and original publications related to the data are linked to the data in an easily accessible way. The eGEOTRACES Electronic Atlas is the visual representation of the IDP2014 data providing section plots and a new kind of animated 3D scenes. The basin-wide 3D scenes allow for viewing of data from many cruises at the same time, thereby providing quick overviews of large-scale tracer distributions. In addition, the 3D scenes provide geographical and bathymetric context that is crucial for the interpretation and assessment of observed tracer plumes, as well as for making inferences about controlling processes

Benefits are From Venus, Costs are From Mars

Given the plethora of available information systems (IS) evaluation techniques, it seems unlikely that yet another technique will address the problems of unsuccessful projects and ineffective management. Rather, more insight into the foundations of evaluation techniques may yield greater benefits. One generally accepted, but largely unexplored, issue concerns objectivity and subjectivity in the assessment of costs and benefits. This research in progress addresses three questions regarding these concepts and their objectivity: (1) how different are costs and benefits, (2) what is the gap between the assessments of costs and of benefits in IS evaluation, and, (3) how could this gap be reduced?lt is demonstrates that, over time, the objectivity of evaluation approaches has diminished as they increasingly assess benefits. As cost measurements remain more objective, assessments that seek to compare costs and benefits become more problematic; hence, benefits are from Venus, costs are from Mars and their orbits are diverging. In order to bring the orbits closer together, a design science methodology is adopted to analyse the divergence's influence on evaluation methods, as well as the 'tweakability' for closing the gap. In a field study, an objectified redesign of Bedell's method (1985), previously considered as subjective, is presented, tested, and compared to the original. In this paper it is argued that narrowing the gap, and particularly the objective measurement of IT benefits, is a prerequisite for a more general acceptance of IT evaluation methods. This identification of objectivity as one of the possible causes for existing methods not being the expected success adds to the foundations upon which IS are evaluated. In addition, gaining insights into the multiple properties of evaluation techniques will enable future research on trade-offs between these properties. The research offers practitioners the possibility of increasing the formality of the assessments. This offers improved potential to address resources allocated to IS and increased credibility of the IS function