Influence of aggregation and measurement scale on ranking a compromise alternative in AHP

Author's pre-print version dated 20. December 2009 deposited in Munich Personal RePEc Archive. Final version published by Palgrave Macmillan; available online at http:// www.palgrave-journals.com/Analytic Hierarchy Process (AHP) is one of the most popular multi-attribute decision aid methods. However, within AHP, there are several competing preference measurement scales and aggregation techniques. In this paper, we compare these possibilities using a decision problem with an inherent trade-off between two criteria. A decision-maker has to choose among three alternatives: two extremes and one compromise. Six different measurement scales described previously in the literature and the new proposed logarithmic scale are considered for applying the additive and the multiplicative aggregation techniques. The results are compared with the standard consumer choice theory. We find that with the geometric and power scales a compromise is never selected when aggregation is additive and rarely when aggregation is multiplicative, while the logarithmic scale used with the multiplicative aggregation most often selects the compromise that is desirable by consumer choice theory

Composite Leptoquarks at the LHC

If electroweak symmetry breaking arises via strongly-coupled physics, the observed suppression of flavour-changing processes suggests that fermion masses should arise via mixing of elementary fermions with composite fermions of the strong sector. The strong sector then carries colour charge, and may contain composite leptoquark states, arising either as TeV scale resonances, or even as light, pseudo-Nambu-Goldstone bosons. The latter, since they are coupled to colour, get a mass of the order of several hundred GeV, beyond the reach of current searches at the Tevatron. The same generic mechanism that suppresses flavour-changing processes suppresses leptoquark-mediated rare processes, making it conceivable that the many stringent constraints may be evaded. The leptoquarks couple predominantly to third-generation quarks and leptons, and the prospects for discovery at LHC appear to be good. As an illustration, a model based on the Pati-Salam symmetry is described, and its embedding in models with a larger symmetry incorporating unification of gauge couplings, which provide additional motivation for leptoquark states at or below the TeV scale, is discussed.Comment: 10 pp, version to appear in JHE

Systematic review of studies generating individual participant data on the efficacy of drugs for treating soil-transmitted helminthiases and the case for data-sharing

Preventive chemotherapy and transmission control (PCT) by mass drug administration is the cornerstone of the World Health Organization (WHO)’s policy to control soil-transmitted helminthiases (STHs) caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm) and hookworm species (Necator americanus and Ancylostama duodenale) which affect over 1 billion people globally. Despite consensus that drug efficacies should be monitored for signs of decline that could jeopardise the effectiveness of PCT, systematic monitoring and evaluation is seldom implemented. Drug trials mostly report aggregate efficacies in groups of participants, but heterogeneities in design complicate classical meta-analyses of these data. Individual participant data (IPD) permit more detailed analysis of drug efficacies, offering increased sensitivity to identify atypical responses potentially caused by emerging drug resistance

Omalizumab efficacy in cases of chronic spontaneous urticaria is not explained by the inhibition of sera activity in effector cells

Omalizumab (OmAb) is a humanized anti-IgE antibody approved for the treatment of chronic spontaneous urticaria (CSU). OmAb's mechanism of action is known to include actions on free IgE and on pre-bound IgE. However, OmAb is equally and rapidly effective against autoimmune and non-autoimmune urticaria where IgE involvement is not clear, suggesting the involvement of additional mechanisms of action. In this study, we sought to investigate the ability of OmAb to inhibit mast cell and basophil degranulation induced by sera from CSU patients. For this purpose, we performed a comparison between the in vitro incubation of sera from CSU patients treated with OmAb and the in vivo administration of OmAb in a clinical trial. We found that OmAb added in vitro to sera from CSU patients did not modify the ability of the sera to induce cell degranulation. Similarly, the sera from patients treated with OmAb in the context of the clinical trial who had a good clinical outcome maintained the capacity to activate mast cells and basophils. Thus, we conclude that the beneficial activity of OmAb does not correlate with the ability of patient sera to induce cell degranulation

VEGF receptors on PC12 cells mediate transient activation of ERK1/2 and Akt: comparison of nerve growth factor and vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) and endostatin are angiogenic and anti-angiogenic molecules, respectively, that have been implicated in neurogenesis and neuronal survival. Using alkaline phosphatase fusion proteins, we show that the PC12 neuronal cell line contains cell membrane receptors for VEGF but not for endostatin and the collagen XV endostatin homologue. Immunocytochemistry confirmed that proliferating and differentiated PC12 cells express VEGF receptors 1, 2 and neuropilin-1. While no functional effects of VEGF on PC12 cell proliferation and differentiation could be observed, a slight VEGF-induced reduction of caspase-3 activity in differentiated apoptotic PC12 cells was paralleled by transient activation of ERK1/2 and Akt. In direct comparison, nerve growth factor proved to be a strikingly more potent neuroprotective agent than VEGF

Neurotrophin receptors expression and JNK pathway activation in human astrocytomas

<p>Abstract</p> <p>Background</p> <p>Neurotrophins are growth factors that regulate cell growth, differentiation and apoptosis in the nervous system. Their diverse actions are mediated through two different transmembrane – receptor signaling systems: Trk receptor tyrosine kinases (TrkA, TrkB, TrkC) and p75^NTRneurotrophin receptor. Trk receptors promote cell survival and differentiation while p75^NTRinduces, in most cases, the activity of JNK-p53-Bax apoptosis pathway or suppresses intracellular survival signaling cascades. Robust Trk activation blocks p75^NTR-induced apoptosis by suppressing the JNK-p53-Bax pathway. The aim of this exploratory study was to investigate the expression levels of neurotrophin receptors, Trks and p75^NTR, and the activation of JNK pathway in human astrocytomas and in adjacent non-neoplastic brain tissue.</p> <p>Methods</p> <p>Formalin-fixed paraffin-embedded serial sections from 33 supratentorial astrocytomas (5 diffuse fibrillary astrocytomas, WHO grade II; 6 anaplastic astrocytomas, WHO grade III; 22 glioblastomas multiforme, WHO grade IV) were immunostained following microwave pretreatment. Polyclonal antibodies against TrkA, TrkB, TrkC and monoclonal antibodies against p75^NTRand phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were used. The labeling index (LI), defined as the percentage of positive (labeled) cells out of the total number of tumor cells counted, was determined.</p> <p>Results</p> <p>Moderate to strong, granular cytoplasmic immunoreactivity for TrkA, TrkB and TrkC receptors was detected in greater than or equal to 10% of tumor cells in the majority of tumors independently of grade; on the contrary, p75^NTRreceptor expression was found in a small percentage of tumor cells (~1%) in some tumors. The endothelium of tumor capillaries showed conspicuous immunoreactivity for TrkB receptor. Trk immunoreactivity seemed to be localized in some neurons and astrocytes in non-neoplastic tissue. Phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were significantly co-expressed in a tumor grade-dependent manner (p < 0.05). Interestingly, a statistically significant (p < 0.05) reverse relationship between Trk receptors LIs and pc-Jun/pJNK LIs was noted in some glioblastomas multiforme.</p> <p>Conclusion</p> <p>In the context of astrocytomas, Trk receptors (TrkA, TrkB, TrkC) expression may promote tumor growth independently of grade. Furthermore, activation of JNK pathway may contribute to progression towards malignancy. Considering the fact that regional tumor heterogeneity may be a limiting factor for immunohistochemical studies, the significance of the reverse relationship between Trk receptors and pc-Jun/pJNK LIs with respect to biological behavior of human astrocytomas requires further evaluation.</p

External Stimuli Mediate Collective Rhythms: Artificial Control Strategies

The artificial intervention of biological rhythms remains an exciting challenge. Here, we proposed artificial control strategies that were developed to mediate the collective rhythms emerging in multicellular structures. Based on noisy repressilators and by injecting a periodic control amount to the extracellular medium, we introduced two typical kinds of control models. In one, there are information exchanges among cells, where signaling molecules receive the injected stimulus that freely diffuses toward/from the intercellular medium. In the other, there is no information exchange among cells, but signaling molecules also receive the stimulus that directionally diffuses into each cell from the common environment. We uncovered physical mechanisms for how the stimulus induces, enhances or ruins collective rhythms. We found that only when the extrinsic period is close to an integer multiplicity of the averaged intrinsic period can the collective behaviors be induced/enhanced; otherwise, the stimulus possibly ruins the achieved collective behaviors. Such entrainment properties of these oscillators to external signals would be exploited by realistic living cells to sense external signals. Our results not only provide a new perspective to the understanding of the interplays between extrinsic stimuli and intrinsic physiological rhythms, but also would lead to the development of medical therapies or devices

Blood pressure gradients and cardiovascular risk factors in urban and rural populations in Abia State South Eastern Nigeria using the WHO STEPwise approach

Background: Developing countries of sub-Saharan Africa (SSA) face a double burden of non-communicable diseases (NCDs) and communicable diseases. As high blood pressure (BP) is a common global cardiovascular (CV) disorder associated with high morbidity and mortality, the relationship between gradients of BP and other CV risk factors was assessed in Abia State, Nigeria. Methods: Using the WHO STEPwise approach to surveillance of chronic disease risk factors, we conducted a populationbased cross-sectional survey in Abia state, Nigeria from August 2011 to March 2012. Data collected at various steps included: demographic and behavioral risk factors (Step 1); BP and anthropometric measurements (Step 2), and fasting blood cholesterol and glucose (Step 3). Results: Of the 2983 subjects with complete data for analysis, 52.1% were females and 53.2% were rural dwellers. Overall, the distribution of selected CV disease risk factors was diabetes (3.6%), hypertension (31.4%), cigarette smoking (13.3%), use of smokeless tobacco (4.8%), physical inactivity (64.2%) and being overweight or obese (33.7%). Presence of hypertension, excessive intake of alcohol, smoking (cigarette and smokeless tobacco) and physical inactivity occurred more frequently in males than in females (p,0.05); while low income, lack of any formal education and use of smokeless tobacco were seen more frequently in rural dwellers than in those living in urban areas (p,0.05). The frequency of selected CV risk factors increased as BP was graded from optimal, normal to hypertension; and high BP correlated with age, gender, smokeless tobacco, overweight or obesity, annual income and level of education. Conclusion: Given the high prevalence of hypertension in this part of Nigeria, there is an urgent need to focus on the reduction of preventable CV risk factors we have observed to be associated with hypertension, in order to effectively reduce the burden of NCDs in Africa.http://dx.doi.org/10.1371/journal.pone.0073403IS

Developmental axon pruning mediated by BDNF-p75NTR–dependent axon degeneration

The mechanisms that regulate the pruning of mammalian axons are just now being elucidated. Here, we describe a mechanism by which, during developmental sympathetic axon competition, winning axons secrete brain-derived neurotrophic factor (BDNF) in an activity-dependent fashion, which binds to the p75 neurotrophin receptor (p75NTR) on losing axons to cause their degeneration and, ultimately, axon pruning. Specifically, we found that pruning of rat and mouse sympathetic axons that project to the eye requires both activity-dependent BDNF and p75NTR. p75NTR and BDNF are also essential for activity-dependent axon pruning in culture, where they mediate pruning by directly causing axon degeneration. p75NTR, which is enriched in losing axons, causes axonal degeneration by suppressing TrkA-mediated signaling that is essential for axonal maintenance. These data provide a mechanism that explains how active axons can eliminate less-active, competing axons during developmental pruning by directly promoting p75NTR-mediated axonal degeneration