Pricing Link by Time

The combination of loss-based TCP and drop-tail routers often results in full buffers, creating large queueing delays. The challenge with parameter tuning and the drastic consequence of improper tuning have discouraged network administrators from enabling AQM even when routers support it. To address this problem, we propose a novel design principle for AQM, called the pricing-link-by-time (PLT) principle. PLT increases the link price as the backlog stays above a threshold β, and resets the price once the backlog goes below β. We prove that such a system exhibits cyclic behavior that is robust against changes in network environment and protocol parameters. While β approximately controls the level of backlog, the backlog dynamics are invariant for β across a wide range of values. Therefore, β can be chosen to reduce delay without undermining system performance. We validate these analytical results using packet-level simulation

TGF-beta 1 induces human alveolar epithelial to mesenchymal cell transition (EMT)

Background: Fibroblastic foci are characteristic features in lung parenchyma of patients with idiopathic pulmonary fibrosis (IPF). They comprise aggregates of mesenchymal cells which underlie sites of unresolved epithelial injury and are associated with progression of fibrosis. However, the cellular origins of these mesenchymal phenotypes remain unclear. We examined whether the potent fibrogenic cytokine TGF-β1 could induce epithelial mesenchymal transition (EMT) in the human alveolar epithelial cell line, A549, and investigated the signaling pathway of TGF-β1-mediated EMT. Methods: A549 cells were examined for evidence of EMT after treatment with TGF-β1. EMT was assessed by: morphology under phase-contrast microscopy; Western analysis of cell lysates for expression of mesenchymal phenotypic markers including fibronectin EDA (Fn-EDA), and expression of epithelial phenotypic markers including E-cadherin (E-cad). Markers of fibrogenesis, including collagens and connective tissue growth factor (CTGF) were also evaluated by measuring mRNA level using RT-PCR, and protein by immunofluorescence or Western blotting. Signaling pathways for EMT were characterized by Western analysis of cell lysates using monoclonal antibodies to detect phosphorylated Erk1/2 and Smad2 after TGF-β1 treatment in the presence or absence of MEK inhibitors. The role of Smad2 in TGF-β1-mediated EMT was investigated using siRNA. Results: The data showed that TGF-β1, but not TNF-α or IL-1β, induced A549 cells with an alveolar epithelial type II cell phenotype to undergo EMT in a time-and concentration-dependent manner. The process of EMT was accompanied by morphological alteration and expression of the fibroblast phenotypic markers Fn-EDA and vimentin, concomitant with a downregulation of the epithelial phenotype marker E-cad. Furthermore, cells that had undergone EMT showed enhanced expression of markers of fibrogenesis including collagens type I and III and CTGF. MMP-2 expression was also evidenced. TGF-β1-induced EMT occurred through phosphorylation of Smad2 and was inhibited by Smad2 gene silencing; MEK inhibitors failed to attenuate either EMT-associated Smad2 phosphorylation or the observed phenotypic changes. Conclusion: Our study shows that TGF-β1 induces A549 alveolar epithelial cells to undergo EMT via Smad2 activation. Our data support the concept of EMT in lung epithelial cells, and suggest the need for further studies to investigate the phenomenon

Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y12 inhibitor. METHODS: This prospective randomized clinical trial included STEMI patients. The standard-treatment group received clopidogrel, while the genotype-guided group were genotyped for CYP2C19 loss-of-function alleles and carriers were prescribed ticagrelor and noncarriers were prescribed clopidogrel. Primary outcome was a combined ischemic and bleeding outcome, comprising myocardial infarction, non-fatal stroke, cardiovascular death, or Platelet Inhibition and Patient Outcomes major bleeding one year after STEMI. RESULTS: STEMI patients (755) were randomized into a genotype-guided- (383) and standard-treatment group (372). In the genotype-guided group, 31 patients carrying a loss-of-function allele were treated with ticagrelor, while all other patients in both groups were treated with clopidogrel. Patients in the genotype-guided group had a significantly lower risk of primary outcome (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.20–0.59,), recurrent myocardial infarction (OR 0.25, 95%CI 0.11–0.53), cardiovascular death (OR 0.16, 95%CI0.06–0.42) and major bleeding (OR 0.49, 95%CI 0.32–0.74). There was no significant difference in the rate of stent thrombosis (OR 0.85, 95%CI 0.43–1.71). CONCLUSION: A genotype-guided escalation of P2Y12 inhibitor strategy is feasible in STEMI patients treated with clopidogrel and undergoing PCI and is associated with a reduction of primary outcomes compared to conventional antiplatelet therapy

Survey of Predatory Coccinellids (Coleoptera: Coccinellidae) in the Chitral District, Pakistan

An extensive survey of predatory Coccinellid beetles (Coleoptera: Coccinellidae) was conducted in the Chitral District, Pakistan, over a period of 7 months (April through October, 2001). A total of 2600 specimens of Coccinellids were collected from 12 different localities having altitudes from 1219.40–2651.63 m. Twelve different species belonging to 9 genera of 3 tribes and 2 sub-families were recorded. Two sub-families, viz, Coccinellinae Latreille, 1807 and Chilocorinae Mulsant, 1846 were identified. The following 8 species belonged to family Coccinellinae Latreille 1807 and tribe Coccinellini Latreille 1807: Coccinella septempunctata Linnaeus, 1758, Hippodamia (Adonia) variegata Goeze, 1777, Calvia punctata (Mulsant, 1846), Adalia bipunctata (Linnaeus, 1758),Adalia tetraspilota (Hope, 1831), Aiolocaria hexaspilota Hope 1851, Macroilleis (Halyzia) hauseri Mader, 1930,Oenopia conglobata Linnaeus, 1758. Only one species namely Halyzia tschitscherini Semenov, 1965 represented tribe Psylloborini of the sub-family Coccinellinae Latreille, 1807. Three species occurred from sub-family Chilocorinae Mulsant 1846 and tribe Chilocorini Mulsant 1846: Chilocorus rubidus Hope, 1831, Chilocorus circumdatus (Gyllenhal, 1808), Priscibrumus uropygialis (Mulsant, 1853). From the aforementioned species 6 were recorded for the first time from Pakistan: Chilocorus circumdatus, Calvia punctata, Adalia bipunctata, Macroilleis (Halyzia) hauseri, Priscibrumus uropygialis, and Oenopia conglobata

Quantitative fibronectin to help decision-making in women with symptoms of preterm labour (QUIDS) part 1: Individual participant data meta-analysis and health economic analysis.

INTRODUCTION: The aim of the QUIDS study is to develop a decision support tool for the management of women with symptoms and signs of preterm labour, based on a validated prognostic model using quantitative fetal fibronectin (qfFN) concentration, in combination with clinical risk factors. METHODS AND ANALYSIS: The study will evaluate the Rapid fFN 10Q System (Hologic, Marlborough, Massachusetts) which quantifies fFN in a vaginal swab. In part 1 of the study, we will develop and internally validate a prognostic model using an individual participant data (IPD) meta-analysis of existing studies containing women with symptoms of preterm labour alongside fFN measurements and pregnancy outcome. An economic analysis will be undertaken to assess potential cost-effectiveness of the qfFN prognostic model. The primary endpoint will be the ability of the prognostic model to rule out spontaneous preterm birth within 7 days. Six eligible studies were identified by systematic review of the literature and five agreed to provide their IPD (n=5 studies, 1783 women and 139 events of preterm delivery within 7 days of testing). ETHICS AND DISSEMINATION: The study is funded by the National Institute of Healthcare Research Health Technology Assessment (HTA 14/32/01). It has been approved by the West of Scotland Research Ethics Committee (16/WS/0068). PROSPERO REGISTRATION NUMBER: CRD42015027590. VERSION: Protocol version 2, date 1 November 2016

Study protocol: quantitative fibronectin to help decision-making in women with symptoms of preterm labour (QUIDS) part 2, UK Prospective Cohort Study.

INTRODUCTION: The aim of the QUIDS study is to develop a decision support tool for the management of women with symptoms and signs of preterm labour, based on a validated prognostic model using quantitative fetal fibronectin (fFN) concentration, in combination with clinical risk factors. METHODS AND ANALYSIS: The study will evaluate the Rapid fFN 10Q System (Hologic, Marlborough, Massachusetts, USA) which quantifies fFN in a vaginal swab. In QUIDS part 2, we will perform a prospective cohort study in at least eight UK consultant-led maternity units, in women with symptoms of preterm labour at 22+0 to 34+6 weeks gestation to externally validate a prognostic model developed in QUIDS part 1. The effects of quantitative fFN on anxiety will be assessed, and acceptability of the test and prognostic model will be evaluated in a subgroup of women and clinicians (n=30). The sample size is 1600 women (with estimated 96-192 events of preterm delivery within 7 days of testing). Clinicians will be informed of the qualitative fFN result (positive/negative) but be blinded to quantitative fFN result. Research midwives will collect outcome data from the maternal and neonatal clinical records. The final validated prognostic model will be presented as a mobile or web-based application. ETHICS AND DISSEMINATION: The study is funded by the National Institute of Healthcare Research Health Technology Assessment (HTA 14/32/01). It has been approved by the West of Scotland Research Ethics Committee (16/WS/0068). VERSION: Protocol V.2, Date 1 November 2016. TRIAL REGISTRATION NUMBER: ISRCTN 41598423andCPMS: 31277

Antiproliferative effects of Tubi-bee propolis in glioblastoma cell lines

Propolis is a resin formed by a complex chemical composition of substances that bees collect from plants. Since ancient times, propolis has been used in folk medicine, due to its biological properties, that include antimicrobial, anti-inflammatory, antitumoral and immunomodulatory activities. Glioblastoma is the most common human brain tumor. Despite the improvements in GBM standard treatment, patients’ prognosis is still very poor. The aim of this work was to evaluate in vitro the Tubi-bee propolis effects on human glioblastoma (U251 and U343) and fibroblast (MRC-5) cell lines. Proliferation, clonogenic capacity and apoptosis were analyzed after treatment with 1 mg/mL and 2 mg/mL propolis concentrations for different time periods. Additionally, glioblastoma cell lines were submitted to treatment with propolis combined with temozolomide (TMZ). Data showed an antiproliferative effect of tubi-bee propolis against glioblastoma and fibroblast cell lines. Combination of propolis with TMZ had a synergic anti-proliferative effect. Moreover, propolis caused decrease in colony formation in glioblastoma cell lines. Propolis treatment had no effects on apoptosis, demonstrating a cytostatic action. Further investigations are needed to elucidate the molecular mechanism of the antitumor effect of propolis, and the study of its individual components may reveal specific molecules with antiproliferative capacity

What Massive Open Online Course (MOOC) Stakeholders Can Learn from Learning Analytics?

Massive Open Online Courses (MOOCs) are the road that led to a revolution and a new era of learning environments. Educational institutions have come under pressure to adopt new models that assure openness in their education distribution. Nonetheless, there is still altercation about the pedagogical approach and the absolute information delivery to the students. On the other side with the use of Learning Analytics, powerful tools become available which mainly aim to enhance learning and improve learners performance. In this chapter, the development phases of a Learning Analytics prototype and the experiment of integrating it into a MOOC platform, called iMooX will be presented. This chapter explores how MOOC Stakeholders may benefit from Learning Analytics as well as it reports an exploratory analysis of some of the offered courses and demonstrate use cases as a typical evaluation of this prototype in order to discover hidden patterns, overture future proper decisions and to optimize learning with applicable and convenient interventions.Comment: Learning, Design, and Technology, Springer International Publishing. (pp. 1-30) (2016

Core Outcome Set for GROwth restriction: deVeloping Endpoints (COSGROVE).

BACKGROUND: Foetal growth restriction (FGR) refers to a foetus that does not reach its genetically predetermined growth potential. It is well recognised that growth-restricted foetuses are at increased risk of stillbirth, foetal compromise, early neonatal death and neonatal morbidity. Later in life, they are prone to health problems, including increased risk of cardiovascular diseases and neurodevelopmental disorders. Interventions for preventing and treating FGR have been studied in many trials, but evidence is often difficult to synthesise and compare because of differences in the selection and definition of outcomes. To enable future trials to measure similar, meaningful outcomes, we are developing two core outcome sets (COS) - one for prevention and the other for treatment of FGR. METHODS: We will review the literature to identify previously reported outcomes. An international panel of relevant stakeholders who have experience of FGR (parent or carer of a baby that was growth restricted, health professional involved in the care of mothers and babies affected by FGR, a person with expertise in FGR research) will rate the importance of each of those outcomes in a series of three sequential online rounds of a Delphi study. Participants will be able to add items to the proposed list in round 1. A final face-to-face consensus meeting will be held with representatives of each stakeholder group at which a final list of outcomes for inclusion in the COS will be agreed. DISCUSSION: The development of COSs in FGR will ensure the collection and reporting of a minimum dataset agreed by stakeholder consensus and will reduce inconsistencies in the reporting of outcomes across relevant trials. Such standardisation in the reporting of outcomes will improve synthesis of evidence and generalisability of knowledge in the future by reducing heterogeneity in outcomes between trials and thus improve the results of systematic reviews and meta-analyses. Ultimately, we hope that the COSs will lead to an improvement in the quality of evidence-based clinical practice, enhance patient care, and improve the quality and consistency of research. TRIAL REGISTRATION: Not applicable. This study is registered in the Core Outcome Measures for Effectiveness (COMET) database

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives