Mechanism of Action and Clinical Attributes of Auryxia® (Ferric Citrate).

Chronic kidney disease (CKD) is a major cause of morbidity and premature mortality and represents a significant global public health issue. Underlying this burden are the many complications of CKD, including mineral and bone disorders, anemia, and accelerated cardiovascular disease. Hyperphosphatemia and elevated levels of fibroblast growth factor 23 (FGF23) have been identified as key independent risk factors for the adverse cardiovascular outcomes that frequently occur in patients with CKD. Auryxia® (ferric citrate; Keryx Biopharmaceuticals, Inc., Boston, MA, USA) is an iron-based compound with distinctive chemical characteristics and a mechanism of action that render it dually effective as a therapy in patients with CKD; it has been approved as a phosphate binder for the control of serum phosphate levels in adult CKD patients treated with dialysis and as an iron replacement product for the treatment of iron deficiency anemia in adult CKD patients not treated with dialysis. This review focuses on Auryxia, its mechanism of action, and the clinical attributes that differentiate it from other, non-pharmaceutical-grade, commercially available forms of ferric citrate and from other commonly used phosphate binder and iron supplement therapies for patients with CKD. Consistent with the chemistry and mechanism of action of Auryxia, multiple clinical studies have demonstrated its efficacy in both lowering serum phosphate levels and improving iron parameters in patients with CKD. Levels of FGF23 decrease significantly with Auryxia treatment, but the effects associated with the cardiovascular system remain to be evaluated in longer-term studies

Adaptive management of Ramsar wetlands

Abstract The Macquarie Marshes are one of Australia’s iconic wetlands, recognised for their international importance, providing habitat for some of the continent’s more important waterbird breeding sites as well as complex and extensive flood-dependent vegetation communities. Part of the area is recognised as a wetland of international importance, under the Ramsar Convention. River regulation has affected their resilience, which may increase with climate change. Counteracting these impacts, the increased amount of environmental flow provided to the wetland through the buy-back and increased wildlife allocation have redressed some of the impacts of river regulation. This project assists in the development of an adaptive management framework for this Ramsar-listed wetland. It brings together current management and available science to provide an informed hierarchy of objectives that incorporates climate change adaptation and assists transparent management. The project adopts a generic approach allowing the framework to be transferred to other wetlands, including Ramsar-listed wetlands, supplied by rivers ranging from highly regulated to free flowing. The integration of management with science allows key indicators to be monitored that will inform management and promote increasingly informed decisions. The project involved a multi-disciplinary team of scientists and managers working on one of the more difficult challenges for Australia, exacerbated by increasing impacts of climate change on flows and inundation patterns

Concentration in Knowledge Output:A Case of Economics Journals

Journals moderate knowledge activity in economics. The activity of publishing article in professional journal forms significant part of knowledge output. Output of economics articles has been growing over the time. We examine an important question: Is there any case of institutional or location concentration in knowledge production? This paper analyses concentration indicators specific to economics journals and explores link between publication process and concentration. The analysis of various concentration measures present evidence for institutional-geographic-area-author concentration in Knowledge production in Economics. High concentration levels indicate possibility of institutional lock-in. The literature provides evidence for myopic refereeing, editorial favouritism and the presence of ‘lock-in’ effect. The achievement in journal publication is influenced by factors like institutional affiliation, propitious circumstances etc. Discussion carried out in this paper hints the possibility of causal link between unfair process and unfair outcome.Knowledge,Lotka's Law,Fourier Series

Evaluation of correlation between myocardial performance index and left ventricular ejection fraction in patients with acute ST-elevation myocardial infarction

Background: In the diagnosis of patients with ST-elevation myocardial infarction (STEMI), prediction of left ventricular systolic function is one of the vital elements. Traditionally, assessment of left ventricular function is focused on measurement of left ventricular ejection fraction (LVEF). But it is load dependent and sensitive to the alterations in preload and after-load. However, myocardial performance index (MPI) demonstrates supremacy over older established indexes. Hence, the purpose of the study is to estimate the correlation between MPI and LVEF in patients with acute STEMI.Methods: A total of 105 consecutive patients underwent conventional estimation of ejection fraction and LV end-systolic volume by a Teichholz method. All patients received 325mg dispersible aspirin, 300mg clopidogrel at the time of admission and streptokinase. Doppler echocardiographic evaluations were performed at presentation, immediately after thrombolysis (90 minutes) and before discharge on 3rd to 5th days.Results: The mean patient age was 56.36years and 89 (84.76%) patients were male. A low LVEF of <40%, significantly correlated with higher (worse) MPI at the time of presentation (P= 0.04). LVEF showed improvement after thrombolysis, moreover it was significantly higher at 0' (P= <0.03) and 3rd day (P= 0.05) in patients with MPI <0.5.Conclusions: A significant correlation was found between left ventricular ejection fraction and myocardial performance index; lesser the left ventricular ejection fraction, higher the myocardial performance index. However, myocardial performance index could not predict adverse cardiac events during the hospital stay

Morphological filtering on hypergraphs

The focus of this article is to develop computationally efficient mathematical morphology operators on hypergraphs. To this aim we consider lattice structures on hypergraphs on which we build morphological operators. We develop a pair of dual adjunctions between the vertex set and the hyper edge set of a hypergraph H, by defining a vertex-hyperedge correspondence. This allows us to recover the classical notion of a dilation/erosion of a subset of vertices and to extend it to subhypergraphs of H. Afterward, we propose several new openings, closings, granulometries and alternate sequential filters acting (i) on the subsets of the vertex and hyperedge set of H and (ii) on the subhypergraphs of a hypergraph

Effects of Alternaria alternata f.sp. lycopersici toxins on pollen

Effects of the phytotoxic compounds (AAL-toxins) isolated from cell-free culture filtrates of Alternaria alternata f.sp. lycopersici on in vitro pollen development were studied. AAL-toxins inhibited both germination and tube growth of pollen from several Lycopersicon genotypes. Pollen from susceptible genotypes, however, was more sensitive for AAL-toxins than pollen from resistant plants, while pollen of species not belonging to the host range of the fungus was not significantly affected by the tested toxin concentrations. AAL-toxins elicit symptoms in detached leaf bioassays indistinguishable from those observed on leaves of fungal infected tomato plants, and toxins play a major role in the pathogenesis. Apparently, pathogenesis-related processes and mechanisms involved in disease resistance are expressed in both vegetative and generative tissues. This overlap in gene expression between the sporophytic and gametophytic level of a plant may be advantageously utilized in plant breeding programmes. Pollen may be used to distinguish susceptible and resistant plants and to select for resistances and tolerances against phytotoxins and other selective agents.

Stereoselective synthesis of a Glc-NAc conjugate as potential modulator of carbohydrate metabolism and Regio- and stereoselective behaviour of carbapyranose 1,2-epoxides with α-gluco and β-manno configuration

The first part of the present work thesis concerns the synthesis of a Glc-NAc-Conjugated Lactate Dehydrogenase Inhibitor as promising anticancer agent. It was widely demonstrated that solid tumors have an enormous consumption of glucose and are characterized by a “metabolic switch”, because tumor cells use as principal source of energy aerobic glycolysis, instead of oxidative phosphorylation. Besides, cancer cells overexpress the glucose transporter GLUT-1 and enzymes of glycolysis, including Lactate Dehydrogenase Isoform A (LDH-A), which has recently emerged as a new potential target in the anticancer therapy, because of its key role in glycolysis progression. On the basis of these evidences, N-hydroxyindole-based (NHI) LDH-A inhibitors were synthesized in our Department. Recently the research team where I carried out my thesis converted one of these NHI-based LDH-A inhibitors into the corresponding glucose-conjugate and the preliminary studies on its anticancer activity demonstrated that this activity depends on a dual-targeting mechanism, which involves both LDH-A and glucose transporter GLUT-1. On account of this, our goal was synthesizing the corresponding Glc-NAc-conjugate, since the N-acetylglucosamine group, as reported, plays a very important biological role and appears to be involved in determining some features of cancer cells. The second part of this work thesis concerns regioselective studies of the nucleophilic addition reactions to carbapyranose-1,2-epoxide with α-gluco and β-manno configuration. Ring-opening reactions of carbapyranose-1,2-epoxide with β-manno configuration had been widely studied because these epoxides were opened efficiently with attack at C(1) (sterically and electronically favoured) to give 1,2-trans-diaxial carba-α-manno derivatives with both oxygen and nitrogen nucleophiles. Instead carbapyranose-1,2-epoxide with α-gluco configuration did not give such good results, because nucleophiles attack was often unregioselective. Precedent studies, finalyzed to the synthesis of useful α-manno glycoconjugates confirmed these kinds of behaviour, besides in our studies on epoxides with α-gluco configuration it was observed an undesired intramolecular addition process with the internal nucleophile C(5)-CH2OR, that allows the formation of a bicyclic byproduct. The first goal of my thesis was to minimize or to avoid the formation of this bicyclic byproduct, in order to better study and direct the stereo- and regioselectivity of nucleophilic addition reaction on these substrates. For these reasons, first we introduced different bulky protecting groups on the C(6) position, then, we introduced a deoxy-methyl group on C(6) position. On the one hand, introduction of bulky protective groups on C(6) position still have not allowed to obtain regioselective results in nucleophilic addition reactions with O-nucleophiles, however reduced formation of the bicyclic compound was achieved. On the other hand, the introduction of a methyl substituent on C(5) position completely avoids the formation of the bicyclic compound but still affords unregioselective results in nucleophilic addition reactions. More interesting, the use of alcohols different from MeOH efficiently influences the regio- and stereoselectivity of the ring opening process. A very nice result was obtained under methanolysis using LiClO4 as the coordinating agent: in these reaction conditions we observed a completely C(1) regio- and stereoselective nucleophilic addition process

Essays on the Impact of Antitrust Regulation on Corporate Mergers and Divestitures

A merger requires at least one of two separate yet equally important sets of negotiations. The first involves merging parties to discuss issues related to the terms of the merger, including target firm\u27s valuation. The second resolves disputes between the merging parties and the government regulatory agency over the potential anticompetitive impact of the merger. In the first essay, I investigate the probability of completing an acquisition deal conditional on the government approval by applying a nested logit model. My results support the findings of Eckbo (1985), Coate, Higgins, and McChesney (1990), and Coate (2005) that mergers that are expected to increase market concentration are more likely to be challenged by the government. Consistent with Officer (2003) and Bates and Lemmon (2003), I find that including target termination fees is significantly positively related to the probability of completion irrespective of whether the deal is challenged or not. However, I document that including target termination fees deters competitive bidding only if the deal was challenged and leads to higher bid premium to the target firm only if the deal was not challenged. Conditional on not being challenged, acquirer\u27s investment opportunities and the relative size of acquirer and target firms are significantly positively related to the probability of completion, while target investment opportunities and the existence of multiple bidders are significantly negatively related to the probability of completion. Conditional on the merger being challenged, acquirer\u27s investment opportunities and the existence of target termination fees are positively related to the probability of completion and only the existence of multiple bidders is negatively related to the probability of completion. In the second essay, I study the impact of asset sales on the firm\u27s focus level, information asymmetry, and operating performance. I find that following a merger facilitating asset sale the firm becomes more diversified, its information asymmetry increases, and its operating performance does not change while following a non merger related asset sale, the firm becomes more focused, its information asymmetry decreases, and its operating performance improves significantly