Dynamics of conflicts in Wikipedia

In this work we study the dynamical features of editorial wars in Wikipedia (WP). Based on our previously established algorithm, we build up samples of controversial and peaceful articles and analyze the temporal characteristics of the activity in these samples. On short time scales, we show that there is a clear correspondence between conflict and burstiness of activity patterns, and that memory effects play an important role in controversies. On long time scales, we identify three distinct developmental patterns for the overall behavior of the articles. We are able to distinguish cases eventually leading to consensus from those cases where a compromise is far from achievable. Finally, we analyze discussion networks and conclude that edit wars are mainly fought by few editors only.Comment: Supporting information adde

Topiramate plus nortriptyline in the preventive treatment of migraine: a controlled study for nonresponders

A sizeable proportion of migraineurs in need of preventive therapy do not significantly benefit from monotherapy. The objective of the study is to conduct a randomized controlled trial testing whether combination therapy of topiramate and nortriptyline is useful in patients who had less than 50% decrease in headache frequency with the use of the single agents. Patients with episodic migraine were enrolled if they had less than 50% reduction in headache frequency after 8 weeks of using topiramate (TPM) (100 mg/day) or nortriptyline (NTP) (30 mg/day). They were randomized (blinded fashion) to have placebo added to their regimen, or to receive the second medication (combination therapy). Primary endpoint was decrease in number of headache days at 6 weeks, relative to baseline, comparing both groups. Secondary endpoint was proportion of patients with at least 50% reduction in headache frequency at 6 weeks relative to baseline. A total of 38 patients were randomized to receive combination therapy, while 30 continued on monotherapy (with placebo) (six drop outs in the combination group and three for each single drug group). For the primary endpoint, mean and standard deviation (SD) of reduction in headache frequency were 4.6 (1.9) for those in polytherapy, relative to 3.5 (2.3) for those in monotherapy. Differences were significant (p < 0.05]. Similarly, 78.3% of patients randomized to receive polytherapy had at least 50% headache reduction, as compared to 37% in monotherapy (p < 0.04). Finally we conclude that combination therapy (of TPM and NTP) is effective in patients with incomplete benefit using these agents in monotherapy

An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis

Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a 'Cancer Genes Network', a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major complications in cancers, namely, metastasis. The results on genes that play generic roles in cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have broader implications in understanding the role of molecular regulators in mechanisms of cancers. Specifically, our study provides a set of potential targets that are of ontological and regulatory relevance to secondary bone cancer.Comment: 54 pages (19 pages main text; 11 Figures; 26 pages of supplementary information). Revised after critical reviews. Accepted for Publication in PLoS ON

Acute Migraine Therapy: New Drugs and New Approaches

The conceptual shift of our understanding of migraine from a vascular disorder to a brain disorder has dramatically altered the approach to the development of new medicines in the field. Current pharmacologic treatments of acute migraine consist of nonspecific and relatively specific agents. Migraine-specific drugs comprise two classes, the ergot alkaloid derivatives and the triptans, serotonin 5-HT1B/1D receptor agonists. The ergots, consisting of ergotamine and dihydroergotamine (DHE), are the oldest specific antimigraine drugs available and are considered relatively safe and effective. Ergotamine has been used less extensively because of its adverse effects; DHE is better tolerated. The triptan era, beginning in the 1990s, was a period of considerable change, although these medicines retained vasoconstrictor actions. New methods of delivering older drugs include orally inhaled DHE and the transdermal formulation of sumatriptan, both currently under study. Novel medicines being developed are targeted at neural sites of action. Serotonin 5-HT1F receptor agonists have proven effective in phase II studies and have no vascular actions. Calcitonin gene-related peptide (CGRP) receptor antagonists are another promising nonvasoconstrictor approach to treating acute migraine. Olcegepant (BIBN4096BS) and telcagepant (MK-0974) have been shown to be safe and effective in phase I, II, and (for telcagepant) phase III clinical trials. Other targets under investigation include glutamate (AMPA/kainate), TRPV1, prostanoid EP4, and nitric oxide synthase. With new neural targets and the potential for therapeutic advances, the next era of antimigraine medications is near

CONSORT recommendations in abstracts of randomised, controlled trials on migraine and headache

A CONSORT statement on the content of abstracts of randomised, controlled trials (RCTs) was published in 2008. I therefore reviewed the abstracts from 2009 to 2010 published on RCTs in Cephalalgia, Headache and other (non-headache) journals. The following items were reviewed: number of patients, reporting of response either in percentages or absolute values, the use of p values, and effect size with its precision. The latter was recommended in the CONSORT statement. A total of 46 abstracts were reviewed and effect size with 95% confidence intervals was only reported in seven abstracts. The influence of the CONSORT statement on reporting in abstracts has so far only had a limited influence on the headache literature

Why pharmacokinetic differences among oral triptans have little clinical importance: a comment

Triptans, selective 5-HT1B/1D receptor agonists, are specific drugs for the acute treatment of migraine that have the same mechanism of action. Here, it is discussed why the differences among kinetic parameters of oral triptans have proved not to be very important in clinical practice. There are three main reasons: (1) the differences among the kinetic parameters of oral triptans are smaller than what appears from their average values; (2) there is a large inter-subject, gender-dependent, and intra-subject (outside/during the attack) variability of kinetic parameters related to the rate and extent of absorption, i.e., those which are considered as critical for the response; (3) no dose-concentration–response curves have been defined and it is, therefore, impossible both to compare the kinetics of triptans, and to verify the objective importance of kinetic differences; (4) the importance of kinetic differences is outweighed by non-kinetic factors of variability of response to triptans. If no oral formulations are found that can allow more predictable pharmacokinetics, the same problems will probably also arise with new classes of drugs for the acute treatment of migraine

Area under the curve of methotrexate and creatinine clearance are outcome-determining factors in primary CNS lymphomas

Although high-dose methotrexate (HD-MTX) is the most effective drug against primary CNS lymphomas (PCNSL), outcome-determining variables related to its administration schedule have not been defined. The impact on toxicity and outcome of the area under the curve (AUC(MTX)), dose intensity (DI(MTX)) and infusion rate (IR(MTX)) of MTX and plasmatic creatinine clearance (CL(crea)) was investigated in a retrospective series of 45 PCNSL patients treated with three different HD-MTX-based combinations. Anticonvulsants were administered in 31 pts (69%). Age >60 years, anticonvulsant therapy, slow IR(MTX) (1100 micromol hl(-1) were independently associated with a better survival. Slow CL(crea) and high AUC(MTX) are favourable outcome-determining factors in PCNSL, while slow CL(crea) is significantly related to higher toxicity. AUC(MTX) significantly correlates with age, anticonvulsant therapy, IR(MTX), and DI(MTX). These findings, which seem to support the choice of an MTX dose >/=3 gm(-2) in a 4-6-h infusion, every 3-4 weeks, deserve to be assessed prospectively in future trials. MTX dose adjustments in patients with fast CL(crea) should be investigated

Identifying potential survival strategies of HIV-1 through virus-host protein interaction networks

Background: The National Institute of Allergy and Infectious Diseases has launched the HIV-1 Human Protein Interaction Database in an effort to catalogue all published interactions between HIV-1 and human proteins. In order to systematically investigate these interactions functionally and dynamically, we have constructed an HIV-1 human protein interaction network. This network was analyzed for important proteins and processes that are specific for the HIV life-cycle. In order to expose viral strategies, network motif analysis was carried out showing reoccurring patterns in virus-host dynamics.Results: Our analyses show that human proteins interacting with HIV form a densely connected and central sub-network within the total human protein interaction network. The evaluation of this sub-network for connectivity and centrality resulted in a set of proteins essential for the HIV life-cycle. Remarkably, we were able to associate proteins involved in RNA polymerase II transcription with hubs and proteasome formation with bottlenecks. Inferred network motifs show significant over-representation of positive and negative feedback patterns between virus and host. Strikingly, such patterns have never been reported in combined virus-host systems.Conclusions: HIV infection results in a reprioritization of cellular processes reflected by an increase in the relative importance of transcriptional machinery and proteasome formation. We conclude that during the evolution of HIV, some patterns of interaction have been selected for resulting in a system where virus proteins preferably interact with central human proteins for direct control and with proteasomal proteins for indirect control over the cellular processes. Finally, the patterns described by network motifs illustrate how virus and host interact with one another

Effect of invader removal: pollinators stay but some native plants miss their new friend

Removal of invasive species often benefits biological diversity allowing ecosystems’ recovery. However, it is important to assess the functional roles that invaders may have established in their new areas to avoid unexpected results from species elimination. Invasive animal-pollinated plants may affect the plant–pollination interactions by changing pollinator availability and/or behaviour in the community. Thus, removal of an invasive plant may have important effects on pollinator community that may then be reflected positive or negatively on the reproductive success of native plants. The objective of this study was to assess the effect of removing Oxalis pescaprae, an invasive weed widely spread in the Mediterranean basin, on plant–pollinator interactions and on the reproductive success of co-flowering native plants. For this, a disturbed area in central Portugal, where this species is highly abundant, was selected. Visitation rates, natural pollen loads, pollen tube growth and natural fruit set of native plants were compared in the presence of O. pes-caprae and after manual removal of their flowers. Our results showed a highly resilient pollination network but also revealed some facilitative effects of O. pes-caprae on the reproductive success of co-flowering native plants. Reproductive success of the native plants seems to depend not only on the number and diversity of floral visitors, but also on their efficiency as pollinators. The information provided on the effects of invasive species on the sexual reproductive success of natives is essential for adequate management of invaded areas.This work is financed by FEDER funds through the COMPETE Program and by Portuguese Foundation for Science and Technology (FCT) funds in the ambit of the project PTDC/ BIA-BIC/110824/2009, by CRUP Acc¸o˜es Integradas Luso- Espanholas 2010 with the project E10/10, by MCI-Programa de Internacionalizacio´n de la I ? D (PT2009-0068) and by the Spanish DGICYT (CGL2009-10466), FEDER funds from the European Union, and the Xunta de Galicia (INCITE09- 3103009PR). FCT also supported the work of S. Castro (FCT/ BPD/41200/2007) and J. Costa (CB/C05/2009/209; PTDC/ BIA-BIC/110824/2009). The work of V. Ferrero was supported by the Fundacio´n Ramo´n Areces