6 research outputs found
On strategic choices faced by large pharmaceutical laboratories and their effect on innovation risk under fuzzy conditions
ObjectivesWe develop a fuzzy evaluation model that provides managers at different responsibility levels in pharmaceutical laboratories with a rich picture of their innovation risk as well as that of competitors. This would help them take better strategic decisions around the management of their present and future portfolio of clinical trials in an uncertain environment. Through three structured fuzzy inference systems (FISs), the model evaluates the overall innovation risk of the laboratories by capturing the financial and pipeline sides of the risk.Methods and materialsThree FISs, based on the Mamdani model, determine the level of innovation risk of large pharmaceutical laboratories according to their strategic choices. Two subsystems measure different aspects of innovation risk while the third one builds on the results of the previous two. In all of them, both the partitions of the variables and the rules of the knowledge base are agreed through an innovative 2-tuple-based method. With the aid of experts, we have embedded knowledge into the FIS and later validated the model.ResultsIn an empirical application of the proposed methodology, we evaluate a sample of 31 large pharmaceutical laboratories in the period 2008–2013. Depending on the relative weight of the two subsystems in the first layer (capturing the financial and the pipeline sides of innovation risk), we estimate the overall risk. Comparisons across laboratories are made and graphical surfaces are analyzed in order to interpret our results. We have also run regressions to better understand the implications of our results.ConclusionsThe main contribution of this work is the development of an innovative fuzzy evaluation model that is useful for analyzing the innovation risk characteristics of large pharmaceutical laboratories given their strategic choices. The methodology is valid for carrying out a systematic analysis of the potential for developing new drugs over time and in a stable manner while managing the risks involved. We provide all the necessary tools and datasets to facilitate the replication of our system, which also may be easily applied to other settings
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
Cell viability evaluation of transdifferentiated endothelial-like cells by quantitative electron-probe X-ray microanalysis for tissue engineering
Development of an efficient vascular
substitute by tissue engineering is strongly dependent on
endothelial cell viability. The aim of this study was to
evaluate cell viability of transdifferentiated endotheliallike cells (Tr-ELC) by using for the first time electron
probe X-ray microanalysis (EPXMA), not only to
accurately analyze cell viability by quantifying the
intracellular ionic concentrations, but also to establish
their possible use in vascular tissue engineering
protocols.
Human umbilical cord Wharton’s jelly stem cells
(HWJSC) and endothelial cells from the human
umbilical vein (HUVEC) were isolated and cultured.
Transdifferentiation from HWJSC to the endothelial
phenotype was induced.
EPXMA was carried out to analyze HUVEC,
HWJSC and Tr-ELC cells by using a scanning electron
microscope equipped with an EDAX DX-4
microanalytical system and a solid-state backscattered
electron detector. To determine total ion content, the
peak-to-local-background (P/B) ratio method was used
with reference to standards composed of dextran
containing known amounts of inorganic salts.
Our results revealed a high K/Na ratio in Tr-ELC
(9.41), in association with the maintenance of the
intracellular levels of chlorine, phosphorous and
magnesium and an increase of calcium (p=0.031) and
sulfur (p=0.022) as compared to HWJSC. Calcium levels
were similar for HUVEC and Tr-ELC. These results
ensure that transdifferentiated cells are highly viable and
resemble the phenotypic and microanalytical profile of
endothelial cells.
Tr-ELC induced from HWJSC may fulfill the
requirements for use in tissue engineering protocols
applied to the vascular system at the viability and
microanalytical levels
The Impact of Failure and Success Experience on Drug Development
It is unclear whether the common belief that experience benefits new product development is driven by decision‐makers allocating more attention to success experience or more attention to failure experience. This article differentiates between the two aforementioned types of experience in order to explore their separate effects on new product development. We find that only late‐stage failure experience improves new product development, that success experience is more beneficial than late‐stage failure experience and that, while others’ related failure experience increases the likelihood of failure, others’ related success experience decreases it. We conducted our research in the context of drug development in the biotech industry and obtained our data from Pharma Projects. We employ logistic regression analysis to model the likelihood that a drug development project results in failure.University College Dublin FoundationPerig