text:
The unfolded von Willebrand factor response in bloodstream: the self-association perspective
- Hailong Yuan†1,
- Ning Deng†2,
- Songmei Zhang1,
- Yange Cao1,
- Qiong Wang1,
- Xin Liu1 and
- Qing Zhang1, 3Email author
© Yuan et al.; licensee BioMed Central Ltd. 2012
Received: 16 July 2012
Accepted: 8 October 2012
Published: 15 October 2012
von Willebrand factor (vWF) is a multimeric glycoprotein essential for hemostasis after vascular injury, which modulates platelet-surface and platelet–platelet interactions by linking platelet receptors to the extracellular matrix and to each other. The crucial role of vWF in platelet function is particularly apparent when hemodynamic conditions create blood flow with high shear stress. Through multiple functional domains, vWF mediates the attachment of platelets to exposed tissues, where immobilized vWF is able to support a homotypic and/or heterotypic self-association. The self-association of vWF is also supported by a rapidly expanding reservoir of novel evidences that the thiol/disulfide exchange regulates vWF multimer size in the blood circulation. Moreover, in addition to proteolysis and reduction of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), the regulation of vWF multimer size and self-association may depend on a disulfide bond reductase activity ascribed to thrombospondin-1 (TSP-1). Along with the classical signaling pathways in activated platelets, evidence is emerging that lipid rafts also play important roles in various phases of hemostasis and thrombosis and facilitate the interaction between the key signaling molecules. Developments in these areas will refine our understanding of the role played by vWF self-association in physiological hemostasis and pathological thrombosis.
Keywordsvon Willebrand factor Self-association Shear force Thiol/disulfide exchange Signaling molecules
vWF is a large multimeric plasma glycoprotein that plays an important role in hemostasis and thrombosis. This protein is encoded by a very large gene (180 kb, 52 exons) located at the tip of the short arm of chromosome 12, region 12p12-l2pter[1, 2]. vWF is synthesized by megakaryocytes and endothelial cells as pre-pro-vWF. The pre-pro-vWF, composed of a 22-amino acid signal peptide, a 741-amino acid propeptide and the 2050-amino acid mature protein[3], undergoes extensive post-translational processing, glycosylation and assembly in the endoplasmic reticulum, Golgi and post-Golgi[3–5]. vWF multimers synthesized in endothelial cells or in megakaryocytes are stored in cytoplasmic granules, which are also called the Weibel-Palade bodies in endothelial cells[6, 7] or at the periphery of platelet α-granules[8]. The mature monomeric protein is a ~250 kDa molecule containing 12 N-linked and 10 O-linked oligosaccharide chains[9]. Analysis of the amino acid sequence shows that each vWF monomer contains modular domains that are arranged in the order D'-D3-A1-A2-A3-D4-B1-B2-B3-C1-C2-CK. Each vWF monomer has binding sites for fibrin, platelet glycoprotein Ib, IIb/IIIa (GPIb, GPIIb/IIIa) and clotting factor VIII (FVIII)[3]. In the flow of circulation, large bundles or filaments of disulfide-linked vWF multimers of 500 to 20,000 kDa have been found[10]. It is believed that under normal conditions the size of vWF multimers is precisely controlled by ADAMTS13-mediated proteolysis of the Tyr1605-Met1606 peptide bond in the A2 domain[11, 12]. Genetic or acquired deficiency of ADAMTS13 causes thrombotic thrombocytopenic purpura (TTP), a life-threatening disease, in which microvascular thrombi forms in arterioles and capillaries[10], while a paucity of large vWF multimers caused by mutations in the A2 domain is associated with the bleeding disorder, type 2A von Willebrand disease (vWD)[3, 13, 14]. Previously, there were a number of studies that focused on the role of ADAMTS13 in regulating vWF size under hydrodynamic shear[15]. Recently, increasing amount of evidences suggest the self-association of vWF may be an additional mechanism regulating the protein size in circulation, implying a critical impact of vWF self-association on hemostasis and thrombosis[16–18]. However, little is known about the mechanism by which plasma vWF self-associates under high shear stress at site of vascular rupture. This article reviewed recent literature on vWF self-association and we provide a summary model to explain dynamic regulation of vWF self-association (by multidomain interaction, hydrodynamic shear force or thiol/disulfide exchange) and its effect on the complex signal pathways of platelet activation.
Functional domain of vWF and the interaction with platelet
The vWF subunit comprises several domains of which specific functions have been identified[3]. The D'-D3 domains are potential binding sites for P-selectin[19, 20] and are involved in vWF multimerization[21]. Much of the functional activity of vWF multimers resides within the three tandem A domains, A1, A2, and A3. The binding of the A1 domain to GPIb, which initiates rolling interactions, is the first step in the formation of a hemostatic plug at the site of vascular injury[22]. Moreover, the A1 domain has binding sites for heparin, the bacterial glycopeptide antibiotic ristocetin, the snake venom botrocetin and collagen[3, 23–28]. The A2 domain situated between A1 and A3 domain lacks long-range disulphide bonds. The cleavage of force-sensing A2 domain by ADAMTS13 depends on hydrodynamic shear force-dependent unfolding of the A2 domain, and occurs at the Tyr1605–Met1606 bond within the A2 domain[11]. The size of the vWF multimers is modulated by the ADAMTS13 domain, depending on the rheological forces and calcium ion[29]. The A3 domain is the binding site for fibrillar collagen type I and III[25, 26, 30]. The structural change of A3 domain enables the binding of the A1 domain to GPIb consisting of a disulfide-linked α chain and β chain[31, 32]. The initial step mediated by A1 domain is followed with platelet activation and stable adhesion via the irreversible interaction between C domain and GPIIb/IIIa by RGDS within the C domain, which initiates and expands the platelet aggregation cascade[22, 33, 34]. The vWF C1 and C2 domains are involved in platelet adhesion to polymerized fibrin at high shear stress[35]. The CK domain is a prerequisite to vWF tail-to-tail dimerization[36]. Thus, the functional domains within vWF are potential elements that mediate intradomain or interdomain interaction contributing to vWF self -association.
Multiple domains interaction contributing to vWF self-association
It has been recently shown that the only binding site for vWFpp in mature vWF is in its D'D3 domain and vWFpp has the ability of partially reducing platelet adhesion and activation by reduce the binding affinity of the VWF-A1 domain for platelet GpIbα[40, 41]. The results presented in this study demonstrated that deletion of the D'D3 region in vWF facilitated the binding of vWF to GPIbα, suggesting an inhibitory role for this region. The isolated D'D3 region inhibited the GPIbα interaction with a vWF deletion mutant lacking this region, indicating that intradomain interactions limit the accessibility of the A1 domain. Interestingly, N-terminal region of the A1 domain (amino acids Gln1238-Glu1260) was also reported to modulates the interaction between vWF and GPIbα[42]. The N-terminal region of vWF between the D4 and cystine-knot domains was visualized for the first time to form a rod at the acidic pH of the trans-Golgi and Weibel-Palade bodies. In addition, the A2, A3 and D4 domains were observed to assembly a raceme with three pairs of opposed, large, flower-like domains by electron microscopy[43]. These observations shed light on the interdomain interaction attributing to vWF self-association that occurs during the biogenesis of vWF prior to its secretion into the vasculature. In addition to mimicking the in vivo environments for vWF assembly, there were reports that the proteolytic vWF-fragments SpII (1366–2050) and SpIII (1–1365) respectively inhibited the interaction between vWF and biotinylated vWF (b-vWF) by 70% and 80%, as measured by ELISA analysis, suggesting that SpII and SpIII contributed to vWF self-association[44]. An interesting hypothesis was proposed that the same multiple-domain interaction accounted for the stabilization of the globular structure of vWF under rest state. Once activated by immobilizing or shear force, homotypic and/or heterotypic region self-association might occur[44]. Despite extensive studies, however, the mechanism by which intradomain interaction mediates vWF self-association with each other has not been clearly elucidated. Further studies are thus required in order to identify the precise nature of the intradomain or interdomain interaction attributing to vWF self-association.
Shear force and functional self-association of vWF
Base on the above findings and considerations, some studies validated that purified plasma vWF multimers significantly increased the numbers of strings on histamine-stimulated human umbilical vein endothelial cells (HUVECs) under flow conditions[57]. It is noteworthy that the sheared plasma vWF molecules resemble polydispersed coils in contrast to the rodlike morphology of unsheared samples[51]. Recently, vWF was observed to transit from a loosely coiled ball to a stretched structure in response to shear force. The unfolding process was reversible since once the hydrodynamic shear force was reduced to 5,000s-1, vWF immediately relaxed back to its compact state[58, 59]. There is other evidence suggesting that relaxation process of stretched vWF bundles formed by hydrodynamic stress proceeded through hopping events between a multitude of minima. The longest relaxation time was found to be dominated by the internal conformations and effective friction within the bundle, consistent with current ideas of vWF self-association[60]. Up to now, little is known about the dynamic and mechanical characteristics of such vWF fibers. Physiological and pathological levels of shear stresses (50 and 100 dynes/cm-2) were demonstrated to modify the vWF adhesion activity by promoting the formation of disulfide bonds which may increase vWF multimer size[61]. It was proposed that high shear stress elongates globular plasma vWF multimers, promotes covalently association of vWF by forming interchain disulfide bonds, and increases binding avidity and bond strength for platelet GPIb.
Thiol/disulfide exchange and vWF self-association
Potential cysteines involved in vWF self-association
Domain region Identified disulfide bond/cysteines in vWF multimers
D' domain
767 ↔ 808
776 ↔ 804
810 ↔ 821
D3 domain
867 ↔ 996
889 ↔ 1031
898 ↔ 993
914 ↔ 921
1060 ↔ 1084
1071 ↔ 1111
1089 ↔ 1091
1126 ↔ 1130
1149 ↔ 1169
1153 ↔ 1165
1196 ↔ 1199
1234 ↔ 1237
889, 898
A domain
A3-D4 domain
1879 ↔ 1904
1899 ↔ 1940
1927 ↔ 2088
D4 domain
1950 ↔ 2085
1972 ↔ 2123
1993 ↔ 2001
C domain
2724 ↔ 2774
2739 ↔ 2788
2750 ↔ 2804
2754 ↔ 2806
2448, 2451
2490, 2491
2453, 2528
The synergistic mechanism of the main platelet receptors involved in vWF self-association
In normal circulation within intact vasculature, most platelets never have the access to interact with the endothelial surface during their whole lifetime. However, at sites of vascular injury, platelets promptly adhere to the subendothelial extracellular matrix bridged by vWF to limit hemorrhage and promote tissue healing[80]. The results were verified by the observation that transient interactions of platelet-receptor GpIb with immobilized vWF mediate the rolling of platelets at sites of vascular damage, during which rolling reduces platelet velocity and prolongs the contact time with reactive components of the cell matrix[90]. Particularly, platelets could readily bind to extremely long "beads-on-a-string" structures of newly released ULvWF formed under laminar flow that were visible by phase-contrast microscopy[13]. It was in line with the study showing that platelets spontaneously bound to a subset of vWF strings secreted from histamine stimulated HUVEC in a GPIb dependent manner[62, 91]. Importantly, platelets adhered to ULvWF fibers expressed P-selectin and bound PAC-1 (antibody against GpIIb/IIIa), suggesting that the adhesion of platelets to ULvWF fibers induced rapid platelets activation[48]. Recent elegant studies showed that fluid shear in circulation could increase the effective size of vWF binding to platelet GpIbα via protein self-association, which triggers mechanotransduction and platelet activation by enhancing the drag force applied on the cell-surface receptor, implying that vWF self-association is necessary for platelet activation (Figure4)[63].
Additionally, lipid rafts may serve as a platform to concentrate activated GpIb-IX-V and GpIIb/IIIa in their respective local membrane when vWF self-association occurs and attaches. The GPIb-IX-V complex was first reported to localize to membrane microdomains by Dorahy et al. in 1996[59], but these researchers did not investigate the functional consequences of this association. Increasing evidence is emerging that GPIb-IX-V and GpIIb/IIIa were reported to localize to lipid rafts by the method of sucrose density centrifugation[92–94]. Although relative quantities of GpIIb/IIIa in raft and non-raft fractions did not change on activated platelet, vWF would increase the percentage of GpIb-IX-V located to lipid raft[93]. Disruption of rafts by cholesterol depletion markedly inhibited virtually every aspect of GPIb-IX-V complex function, which results in the inside-out activation of the integrin GpIIb/IIIa, and subsequent platelet aggregation[93]. We speculated that lipid rafts might play a key role in signaling after engagement of the complex by VWF self-association. Here, a model is proposed to explain effects of lipid rafts formation of on platelet activation upon stimulation by vWF self-association (Figure4). This model requires that GPIb-IX-V complexes be clustered sufficiently close to allow formation of this lipid rafts-ordered complex, and may explain the requirement of rafts for subsequent GPIIb/IIIa activation. This raft association of GPIb-IX-V induced by self-associated vWF would induce GPIIb/IIIa activation in a way different to the outside-in/inside-out signal pathway in platelet activation discussed above. Therefore, vWF self-association may be a cryptic factor in the signaling pathway of platelet.
vWF self-association has been become increasingly appreciated over the past several years. The self-association ability of vWF represents an additional mechanism that the circulating multimers interact in a reversible manner with matrix-bound and endogenous subendothelial vWF under conditions of hydrodynamic shear. Conversely, the association is damped by increasing cleavage by ADAMTS13 under fluid shear stress. This reaction is likely to account for a majority of vWF proteolysis after secretion and determines the distribution of circulating vWF multimers in vivo. The other mechanism that has been shown to alter vWF self-association is the reduction of the disulfide-bonds holding the subunits together, which led to the identification of TSP-1 as a disulfide reductase involved in regulation of vWF multimer size. We speculate that ADAMTS13/TSP-1 and vWF self-association work together to regulate vWF multimer assembly and degradation, and functional imbalances between the two sides are related mechanistically to the problems of bleeding and thrombosis. It has been also indicated that a thiol/disulfide mechanism of self-association of vWF involves in either intra-subunit or inter-subunit vWF disulfide bond formation, suggesting the possibility that the cysteines exposed on plasma vWF or buried in might result in self-association. Above all, vWF self-association binding to GPIb-IX-V may trigger outside-in signals of platelet activation through mechanotransduction applied on the cell-surface receptor. In turn, ligand binding to GpIIb/IIIa is controlled by inside-out signals that modulate receptor conformation and clustering. Further understanding of vWF's dynamic self-association can provide new approaches and theory evidences for a subject with immediate physiological and signaling relevance.
- vWF:
von Willebrand factor
A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13
- GPIb:
Glycoprotein Ib
- GPIIb/IIIa:
Glycoprotein IIb/IIIa
Thrombotic thrombocytopenic purpura
- vWD:
von Willebrand disease
- vWFpp:
vWF propeptide
- WT-vWF:
Wild type vWF
- ULvWF:
Ultra-large vWF
Enzyme-linked immunosorbent assay
- b-vWF:
Biotinylated vWF
- HUVECs:
Human umbilical vein endothelial cells
- PLCγ2:
Phospholipase Cγ2
Inositol 1,4,5 trisphosphate
IP3 receptor
Dense tubular system
- CalDAG-GEFI:
Ca2+ and diacylglycerol regulated guanine nucleotide exchange factorI
Rap1-interacting adaptor molecule.
This work was supported by the National Natural Science Foundation of China (grants 30570785 and 30770923), the Fundamental Research Funds for the Central Universities: SYSU (grants 11lgjc09).and the National High Technology Research and Development Program of China (863 Program: A2009AA02Z112).
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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The Los Angeles Concert and Artist Selection Room
Steinway & Sons is proud to announce the Los Angeles Concert and Artist piano selection facility. This facility offers professional pianists the opportunity to select an instrument from the famous Steinway Concert and Artist piano bank. These unparalleled instruments are prepared to "concert ready" Steinway & Sons standards, thus assuring the artist a piano that will fulfill their performance rental needs.
Or call (310) 652-6666
Concert and Artist Room Features:
- Select from six (6) Steinway & Sons Model D 9 foot concert grands
- Select from four (4) Steinway & Sons Model B 7 foot concert grands
- Artist selection days by appointment only
- Convenient Downtown Los Angeles location by Little Tokyo in the Artist District (1 Mile from Walt Disney Concert Hall and Music Center)
We provide piano rentals to recording studios, concert halls, chamber music organizations & orchestras.

subset: commoncrawl


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Doctor insights on:
Male Fungal Infection
Fungal Infection (Definition)
Fungal infections are clinical conditions in which a person has an infection due to a pathogen called a fungus (in contrast to infections caused by bacteria, viruses, or parasites). Fungal infections occur commonly on the skin (including Jock Itch and Athlete's Foot) and can also cause more serious infections in those ...Read more
I just started using monistat 1 (tioconazole) for a possible male fungal genital infection. How do I know if it's not working and should I keep using for 7 days?
Simple: You know it is working because your symptoms go away. You should use it as per the instructions. If its 7 days, use it for 7 days. ...Read more
I am a 28 yo male. I have always had recurring mouth ulcers and fungal infection on penis glans..Lately also having recurrent eye burns and joint pain?
Multiple symptoms?: Sounds like the symptoms you describe could indicate an std. I would suggest you seek a physician. ...Read moreSee 1 more doctor answer
How long can fungal infections last?
Fungal infections: That depends upon the fungus, where the infection is located and how it is treated. Go and have a doctor look at this. Good luck. ...Read more
How does a person get a fungal infection?
By catching one: An infection is a condition in which a germ enters your body and causes it harm. There are three main categories of germs: viruses, bacteria, and fungi. Fungi are full single cells that can join together into threads. If these enter your body, you can get a fungal infection. You get them by contact with someone who has a fungal infection or just fungus on their skin. ...Read more
What sort of disorder is a fungal infection?
Infection: Fungal infections can occur on the skin (ringworm, some diaper rashes, athlete's foot, others), on nails, in the genitals (yeast infections), in the mouth (thrush), or less commonly internal organs. Different fungi come from different places, they have different symptoms, and are treated different ways. Some require only a cream, some oral medication, and some IV medication. ...Read moreSee 1 more doctor answer
How do I know if I have a fungal infection?
Rash: If you have a fungal infection on the skin, you will see an annula rash (circular) with and elevated scly border. If the infection is under the nails, there with be debris with lifting of the nail. ...Read moreSee 1 more doctor answer
Could skin fungal infection gain resistance?
Skin Fungal Infectio: The short answer is yes, it is possible. However, most skin fungal infections are easily treatable, and actually when they don't seem to respond - it is because they were misdiagnosed. Many types of skin conditions look very similar, and often are ultimately figured out after trying several different medications. Thus, if you are in doubt, go to your dermatologist or pcp for help! ...Read more
What are the symptoms of a fungal infection?
Depends on site: The symptoms of fungal infection depend on the site of infection--skin-lungs-sinus-blood stream-kidneys etc. ...Read more
What can be done to cure fungal infections?
Medication/hygeine: Topical or oral medication as well as steps to mimimize excessive moisture from accumulating and allow proper exposure to air. ...Read more
Infection (Definition)
Infections are invasions of some other organism (fungus, bacteria, parasite) or viruses into places where they do not belong. For instance, we have normal gut bacteria that live within us without causing problems; however, when those penetrate the bowel wall and enter the bloodstream, ...Read more
Men (Definition)
Men are adult members of the male sex. The acropnym men also stands for multiple endocrine neoplasia, a hereditary condition that involves benign and malignant tumors of various glands. There are two main types, men ...Read more
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- Fungal infection near male genital organs
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- Ask a doctor a question free online
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- Treatment for fungal infection on buttocks
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- Talk to a dermatologist online


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Trousers and Shorts
This season it's all about corduroy in our collection of girls trousers. Tootsa MacGinty has designed a bright and funky range of cords for girls up to age 6 which are fully lined in warm jersey cotton and have fun applique animals peeking out of the back pockets. These look fabulous with her statement animal jumpers including the classic fox jumper.
Frugi Snuggle Crawlers, raspberry (0-3Years)
Regular Price: £20.00
Special Price £10.00
Frugi Kneepatch Dungarees, Wheels on the Bus (0-24mths)
Regular Price: £22.00
Special Price £10.00
Frugi Parsnip pants - Diver Blue/ Starfish (0-3 years)
Regular Price: £18.00
Special Price £14.40
Frugi springtime dungarees - garden friends (3m-3y)
Regular Price: £24.00
Special Price £19.20
Frugi, Flower Button Dungarees - Springtime (0-24mths)
Regular Price: £25.00
Special Price £12.50


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Treatment of Refractory Angina Pectoris by Shock Wave Therapy
This trial is active, not recruiting.
|angina pectoris
|extra-corporeal shockwave, anti-hypertensive drugs
|phase 3
|Universal Research Group
|UNIQUIP INTERNATIONAL, Pakistan
|Start date
|February 2008
|End date
|August 2009
|Trial size
|60 participants
|Trial identifier
The purpose of this study is to determine that extracorporeal shock wave therapy (ESWT) is safe and effective for the treatment of refractory angina pectoris.
|United States
|No locations recruiting
|Other countries
|No locations recruiting
|Karachi, Pakistan
|Karachi Institute of Heart Diseases
|no longer recruiting
Study Design
|Endpoint classification
|safety/efficacy study
|Intervention model
|parallel assignment
|open label
|Primary purpose
Primary Outcomes
Alleviation of anginal symptoms
time frame: 06 months
Secondary Outcomes
The change in SPECT in perfusion from baseline to 6 months post-baseline (17 segments model
time frame: 6 months
Eligibility Criteria
Male or female participants from 18 years up to 80 years old.
Inclusion Criteria: - Male or female, 18 years or older. - Diagnosis of chronic stable angina pectoris. Diagnosis is based on medical history, complete physical evaluation, and Exercise Single-Photon Emission Computed Tomography (Exercise SPECT). - Patient has documented myocardial segments with reversible ischemia and or hibernation. - Patient is classified as AP CCS of III or IV. - Patient should be on a stable dosage of medication used to treat angina for at least 6 weeks prior to enrollment. - Patients demonstrates exercise tolerance time (ETT) duration <10 minutes on a modified Bruce protocol on 2 consecutive tests (tests no less than 24 hours and no more than 2 weeks apart), with the second test within 25% of the first (Patients should not be informed of exercise restrictions required for entry into the study). - Patient has refused to undergo another angioplasty or CABG. - Patient has signed an informed consent form. - Patient's condition should be stable and should have a life expectancy of >12 months. - Patient's current and past medical condition and status will be assessed using previous medical history, physical evaluation, and the physicians (principle investigator's) medical opinion. - Newly diagnosed type II diabetes. Exclusion Criteria: - Chronic lung disease including emphysema and pulmonary fibrosis. - Active endocarditis, myocarditis or pericarditis. - Patient is simultaneously participating in another device or drug study, or has participated in any - Clinical trial involving an experimental device or drug, including other drugs or devices enhancing cardiac neovascularization, or any ESWT machine for neovascularization of a competitor company within 3 months of entry into the study. - Patients who are unwilling or unable to cooperate with study procedure. - Patients who are unwilling to quit smoking during the study procedure (including screening phase) - Patients who had myocardial infarction (MI) less than 3 months prior to treatment. - Patients who are diagnosed with a 3rd and 4th degree heart valve disease. - Patient with intraventricular thrombus. - Pregnancy. - Patient with a malignancy in the area of treatment.
Additional Information
|Official title
|Extracorporeal Shock Wave Therapy (ESWT) for the Treatment of Refractory Angina Pectoris
|Principal investigator
|Prof. Abdul Samad, MD
|Patients with advanced CAD frequently have limited symptoms with recurrent angina, angina at low work thresholds, breathlessness, and other debilitating conditions. These patients have often been through several "re-do" coronary bypass procedures and multiple percutaneous coronary interventions. Surgical and interventional options for these patients typically have been exhausted or will result in only partial revascularization. Therefore, therapy remains limited to the use of multiple anti-anginal medications, reduced activity, exertion, and stress level, and significant alteration and limitation of lifestyle. The goal of this emerging approach is to therapeutically induce the growth and development of new vasculature in zones of severe ischemia in the myocardium, with the hope that new capillaries and arterioles generated will connect to remnant existing vasculature. These neovessels are viewed to act as collaterals, perfusing ischemic territories unapproachable by macro procedures such as PCI and/or CABG.
Call for more information
|Principal Investigator
|Trial ID


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I am Michelle Donelan and in May 2015 I was elected as the Member of Parliament for the Chippenham constituency which covers Chippenham, Corsham, Bradford on Avon, Melksham and the surrounding villages.
I have lived in Chippenham for a number of years and in 2014 I bought my very first home in the centre of the town. I have worked overseas and as an International Manager but now I work locally for myself and understand the challenges of small business.
All of my life I have wanted to be represented by someone with whom I can identify. We have too many career politicians and too many political families stuck in the Westminster bubble, far away from real life. We need more real people who have held proper jobs and understand the challenges their voters face.
I want to challenge those in the Westminster bubble and shake up the system. I have never had a "job" in politics. I have always worked for my money in a "real job", managed a tight household budget and I know what it is like to struggle. I was the first in my family to finish University; my father and grandfather did not even finish school. My father taught me to work damn hard and make the most of the opportunities that came my way. This is why I believe an MP's job should be to knock down barriers, open doors and create opportunities for all.
I cannot just comment from the side-lines and expect others to do the heavy lifting. I believe in getting stuck in and getting things done instead of talking about them. So I have set out a clear plan which in five years' time you can judge me against.
I am passionate about our area and love living here; there is a lot to build on. However why should we settle for what we have got – we deserve even better.
I have always been active in the voluntary sector and believe that we must promote and celebrate the amazing local people that give their time for free to help charities and organise community events. I am a Trustee of a local charity – Help Victims of Domestic Violence, a Bradford on Avon Emergency Community Volunteer offering help with disasters like floods and am the Recruitment Officer. I am also on the Steering Group of Wiltshire Carers – working with local employers to find ways to provide more flexible working systems for carers. I am a strong supporter of Doorway and regularly volunteer with them as well as our local Rotary Clubs. I have played an active role helping with community events including Melksham Party in the Park and The Chippenham Sci-Fi event.
I stood to be the Member of Parliament in this constituency, in order to breathe fresh air into government and to ensure that our voice is heard. You can read more about my local plan here.
My key aims for our area:
- More local jobs
- Giving you security in retirement
- Support hardworking families
- Develop a long term plan to rejuvenate our towns
- Protect our countryside
- Target anti-social behaviour
- Champion our local community


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Southern California High Tech Event Calendar
|View By:
|View By:
|Los Angeles #ThinkFWD Chapter Launch
|Date: April 15, 2014
|TLos Angeles #ThinkFWD Chapter Launch. opic of discussion: Can tech rebuild the middle class and the American dream in the 21st century? FWD.us invites you to join leaders in tech, politics and policy on April 15 in Venice, CA for a discussion about the future of the Middle Class and the American Dream in the 21st century. This is an inaugural event in a series of conversations on keeping the United States and its citizens competitive in a global economy. See http://www.fwd.us/field_041514_la_launch_p
|More information: http://www.fwd.us/field_041514_la_launch_p
|Download to Calendar


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Citterio Wine Decanter
Winner of the 2005 Design Plus award, the clean lines of this mouth blown glass decanter look at home alongside nearly any wine glass. The generous space in the decanter's lower part allows the wine ample contact with air, bringing out its flavor and aroma. The well balanced neck and spout allows for easy, drip-less pouring. 64 oz. / 2 liter capacity.
- Designer
- Antonio Citterio +Toan Ngyen
- Country of Design
- Italy
- Year of Design
- 2004
- Dimensions
- 8.5"H x 7.5"D
$ 85.00
Citterio Wine Decanter


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Many of you out there will be searching for cleaner ways to power your vehicles. Perhaps you've found a good source of waste veggie oil – and someone to process it – or maybe you're even growing your own crops to cold press for fuel. Perhaps, like me, you're doing neither but want to wean yourself off fossil fuels and suck up some bio-diesel instead. So what are the options for the South Westerly diesel driver?
If you own a diesel vehicle you can either convert your engine to run on pure veggie oil (rape seed oil is the best) or you can forget the conversion and buy specially prepared biodiesel to pour straight into your tank. (Always check with your manfacturer that your car/van/truck can run on biodiesel – ed).
Biodiesel is made from waste veggie oil, making it cheaper than ordinary diesel and carbon neutral. I looked into sourcing it in the South West, and discovered that within spitting distance of my floating home, is a supplier. Biosulis produce biodiesel that I can put straight into my engine as a good alternative to my regular boat-yard diesel. The bio-fuel is made from recycled waste oil collected from local chip shops and restaurants and is available straight from their pump at the processing plant in Radstock. At 91p per litre, you really can't argue with this. What's more, if you take usable waste oil with you for them to process, there's a litre discount of 5p.
So I ask myself… how do you make a litre of waste chip oil into a litre of fuel for any diesel engine? Why are people getting engine conversions to run on pure vegetable oil, when it's so simple to fill up on bio-fuel? And so to the facts. Pure vegetable oil is too thick to run in a normal diesel engine. Which means that in order to use it as a fuel source, you've either got to thin it down, by removing some of the glycerine (as done at Biosulis, resulting in a useful by-product – soap!), or you have to heat it up, by making some modifications to your engine.
There are two main types of engine conversion. The two-tank conversion involves running with one tank of normal diesel and one of veg oil. You use the regular diesel to start up, warm up and shut down the engine. Once the engine is warm from the mineral diesel, you swap the fuel source over to veg oil, which is also now warm and runny, and perfect for fuelling that engine.
The other type of conversion is commonly known as an Elsbett after its German manufacturer. The original Elsbett conversion involves changing the injection pump, glow plugs, electric pre-heating element, electric control relays and adding an aluminium plate heat exchanger in your engine. The basic result of this is to preheat the vegetable oil before ignition and change the way the fuel is sprayed into the engine, to deal with the thickness of the oil.
Conversions are more costly (£500-£1000 for a kit on the internet or £1500-2000 for installation by reputable eco-mechanics), but once done, they allow you to run on pure veg oil from whatever source you choose (be that Lidls or your local organic farmer's market). If you are planning to hold on to your motor for a year or two, in the long run, you will save a packet in fuel costs.
When buying veg oil to put in a converted engine, you are obliged to make a Duty Return to the Customs & Excise at a rate of 50p per litre. If you make your own biodiesel for personal use, you get a tax-free personal allowance of up to 2,500 litres (or 25,000 miles in a car) every year, as long as you can prove your fuel is decent quality. After that, you must pay 50p tax per litre of fuel produced. If you buy biodiesel at the pump, it's the producer who pays the tax, at a rate of 28.3p per litre.
While biodiesel producers hark the benefits of recycling waste chip fat, engine converters emphasise chemical-free production, fuel autonomy and decentralisation in production, processing and use. I wonder who's gonna get to eco-heaven first…
Hmmm now let me see… Biosulis run their processor on their own generator, running on their own fuels. Carbon-neutral they say. Recycled fat – I like it. Bio-Power in Plymouth, also selling recycled chip oil biofuel (88p per litre) say they cannot get enough of the stuff. In fact used fat dealers (is that the right word?) are exporting our British chip oil to Europe where biofuel processors will pay more on the litre (as they have no tax to pay). 'Cold-presses everywhere' is the message from Matt at Brighton-based Blooming Futures… "In Germany everybody's doing it. There are over 400 presses and the environmental footprint is next to nothing," he says.
Biosulis, Radstock 01761 411011, biosulis.co.uk
Plymouth Biofuels Ltd, 01286 830312, biopower.co.uk
Blooming Futures (Brighton-based conversions with strong DIY ethic): bloomingfutures.com
West Wales conversions: vegoilmotoring.com
Listings of biodiesel suppliers across the UK: biodieselfillingstations.co.uk
Schnews How To article:
How To site (veg oil & vehicle conversion): journeytoforever.org
Book: "From the Fryer to the Fuel Tank: The Complete Guide to Using Vegetable Oil as an Alternative Fuel" by Joshua Tickell.
First published issue 48 (Spring 2007)
Written by Kate Burrell
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The lazer blue glass of this fascinating watch adds even more to the iconic design - 4.3cm case, black dial with yellow features, red tipped second hand and index date function on a 4.1cm bracelet. Water resistant 50m.
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Conveniant little bakery. I found pies here to be of average quality. Bread and rolls really nice and I cant comment on the cakes. I have tried a few pies from here both meat varietus and their vegedable. Yhe meat varietys i would raye o.k., the vege was very bland and tastless I would not buy again. Bakery does seem clean and staff are friendly. I believe this bakery use to be related to one at Urunga as many products were the same but this may of since changed. I know it is pretty standard for bakerys to freeze their pies but it is always nicer to think they are all freshly made the night or morning before. Parking is definatly no problem at this bakery as it has its own car park that it shares with only a gew oyhwr little local shops. Over all pretty good value for money as priced well.
Approximate cost: $2.50-5.50
Love this bread shop, it has beautiful bread and pastries and I especially love their sausage rolls and cost around $2.20, very happy with the quality of their food and cheap prices and friendly staff.
My favorite bakery in coffs they have a great selection of bread, rolls, sweets, pies, sausage rolls, pasties, sanwiches. All their food is is delishousand well priced and the staff are super friendly :)
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OVER THE RAINBOW IIAbout this photograph
Photography is a means of exploring, inventing, escaping. Photography is a refuge for me, affirms Italian artist, Cristina Coral. Delicate and poetic, the young woman's work seems to exhibit her inner emotions by bringing her observations of reality into the light of day, her inner thoughts, and the emotional baggage of her memories. For her, each image has a soul and this one in particular, which completes her series "Over the Rainbow". It was taken in 2014 in Italy, after a rainy day, as a rainbow stood out in the background, through the clouds. The female model, in a bathing suit, is making the most of summer to charge her batteries by a swimming pool dating from the 1930s. The natural lighting gives crucial intensity to Cristina Coral's compositions, who captures dreamlike moments outside of time. She thus opens up the doors of a mysterious world to us, on the borders of her imagination.
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The artist
Italian artist Cristina Coral no longer needs an introduction. Her works have illustrated the most prestigious international magazines, such as Vogue, Lens Culture, Huffington Post, Wall Street Journal, and L'oeil to name but a few. In addition to her exhibitions in Italy, the photographer has also won numerous awards since 2014 at the Prix de la Photographie in Paris, the International Photography Awards in Los Angeles, and at the Sony World Photography Awards in London. Well known for her dreamlike portraits captured in spaces and landscapes full of silence, intimacy, and memories, her approach to photography has been self-taught.


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Thank you for your interest in Cody, Wyoming, one of the best small towns in America. Just 50 miles from Yellowstone's East Gate and 85 miles from the NE Gate, Cody sits on the doorsteps of nearly unlimited recreational opportunities. Our businesses are ready to help you whether you're visiting Cody, planning a move here, or have been a lifetime resident.
If you need assistance, please don't hesitate to call us at 1-307-587-2777, email us at email@example.com or stop by our year-round visitor center.
The annual Wild West Extravaganza is coming up July 2-4, 2017. If you're an arts/crafts or food vendor and are interested in applying, please download this form and return it to us along with your payment. Deadline is May 1st.
Experience Cody / Yellowstone Country
For centuries, Buffalo Bill's Cody / Yellowstone Country has been a natural gathering place. Buffalo Bill's legacy remains in Cody, Wyoming, east gateway to Yellowstone National Park, as do the natural wonders and wildlife that make a visit to Cody, Wyoming ...


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Sea Breeze Cardigan
- Product Information
DetailsWear this little jacquard cardigan on its own over jeans with the sleeves pushed up, or on your shoulders over a crisp white shirt. Elbow length sleeves finished in a ribbed cuff.
- 60% Pima Cotton 40% Modal
- Centre back 22.5"
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You can now have easy access to your tickets through the free mobile app. Download the app to buy your tickets and have access to all your sales.
Consider chartering a boat for your next outing, party, fundraiser, or celebration. Make it memorable with a stop in front of the Statue of Liberty. Vessels range in size to accommodate almost any type of function.
Hunters Point South is one of approximately ten neighborhoods that make up Long Island City, one of the most vibrant parts of Queens. With a thriving arts community and an up-and-coming culinary culture, this area is worth exploration. It has one of the highest concentrations of studios, art galleries, performance spaces and art institutions in New York City outside of Manhattan. Not as gentrified as its Greenpoint and North Williamsburg counterparts, some of the neighborhoods (Hunters Point included) may feel like you're finding hidden gems, which you just might be if you're lucky enough to stumble upon 5 Pointz, MoMA PS1, The Museum of the Moving Image, or the Chocolate Factory Theater. Long Island City is a neighborhood not to be missed.


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Ornette Blouse
Long sleeve blouse. V-neckline. Scarf detail. Single button at cuff.
Model is 175 cm – 5'8'' and wears a size 0.
Tailored with love in Canada
Body: Solid silk
100% silk
Judith & Charles offers worldwide shipping using various methods. click here for more details
We accept returns within 21 days of your receipt for regular price items, 7 days for all SALE items. Click here for more details


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The Southern Living Guide to Mayonnaise BrandsEssential reading on a most essential condiment
From Madagascar, this striking palm grows 30 to 40 ft. tall; comes in blue and green forms. The fan-shaped fronds are each up to 10 ft. wide, making a round leaf crown about 25 ft. wide. The blue form is better inland because it's more tolerant of heat and cold, while the frost-intolerant green form excels along the coast. Grow where its low, stout trunk and shapely canopy can show off, as in rows along a driveway or as accent in a lawn.


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Web Stock India
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Great for quick tasty vegan lunch or dinner when.you don't have time to cook. Also, the french fries are awesome!
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3 Days in Vienna
Great for quick tasty vegan lunch or dinner when.you don't have time to cook. Also, the french fries are awesome!
Falleria is at metro stop. Foods itself is vegans as we had falafel better is a joint called pita box . This is across the road from the metro and fillings for falafels can be chosen yourself.
The concept is that you get falafel and bread, and you get to choose from a very wide variety of other ingredients to add, like olives, salads, grilled aubergines, many different types of humus (chili, mango, ...), feta cheese and others. They change the options regally. It's a nice concept, and tastes very good at a nice price. I think... More
Very friendly service and tasty chicken pita breads. Help yourself to as much salad as can go inside the pita.
Great food with im usually eat for takeaway. Lovely service team, a lot of options to eat falafel, good vegan hot dog and soup! Really recommend to try 👍🏻👍🏻
The world needs more such places. If you're a hungry vegetarian (and not) that doesn't want to spend a fortune, places like Falaferia are just what you need. Finding the place is the only tiny little problem (it's well hidden on the several levels of the Train/Metro station) but other than that no real complaints. The food was excellent, the... More
Being in Vienna for more than an year and being vegetarian we (me and my wife) always used to look for a good veg. option. Falafals were a very good friends of us and we always used to look for more Falafal outlets. We tried several places, but believe me this one was the best and as soon as we... More
I have one or two go to places in the UK for falafel so thought I'd give it a go, expecting it not to compare, but really was extremely tasty. The falafel itself is a very nice consistency and flavour + good selection of toppings, friendly staff and reasonably friendly FYI this shop has changed its name. It is now... More
Plenty of Imbiss stands have falafel, but this one is absolutely the BEST! Fresh food, friendly staff, delicious!
It's not always easy to find good, healthy and balanced Vegetarian meals at a good price, especially not in Vienna with its characteristic "Vienna sausages" and "Wiener Schnitzel". However, there is an exception to every rule. If you're looking for a rather undiscovered place and want to mingle with locals, this is an insider tip for you. As for the... More
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floating strainer News
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Related terms for "floating strainer ": strainer news , containment floating strainer news
GF Piping Systems has introduced the new generation Type 561/562 Cone Check Valve and the Type 591/595 Vent and Bleed Valve Series featuring a new spherical cone shape design that offers improved flow characteristics and leak-proof operating performance. Available in sizes from 3/8" – 4", customers can select from PVC, CPVC, PROGEF Standard, ...
Following the highly successful launch of the revolutionary Qdos 30 peristaltic metering pump, Watson-Marlow Pumps Group is now introducing the larger Qdos 60 model. This innovative and versatile new pump is designed to save costs in chemical metering applications thanks to its inherent higher accuracy metering. The addition of Qdos 60 expands the range to incorporate ...
Goulds Water Technology (GWT), a Xylem brand, introduces the GSP0511 Cast Iron Sump Pump ½ Horsepower Model, engineered to provide homes with high quality protection from water damage. ...
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text: 06 Sep Miso Concrete Firebowl – Watch It Burn Posted at 16:23h in Fire Pits by khai 0 Likes Share Here is a Miso Firebowl in Dove with Light Grey River Rock Topping. This fire pit utilizes a manually-lit, natural gas burner which is the burner that is used in most of our non-linear fire pits. RECENT POSTS Feature Project – Glencairn Addition – Outdoor Indoor in the City Feature Project – Galleria Marchetti – 72 Feet of Fire Feature Project – Chalet 1864 – Firebowl in the French Alps Feature Project – Hillside Pool SEARCH Search for: CATEGORIES Concrete Tiles (4) FAQ (5) Feature Projects (14) Fire Pits (42) Fireplace Design (9) Fireplaces (2) Paloform (19) Things We Love (3)


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Burberry Shoes & Accessories Bankston Grain Leather Holdall
£1,595.00 Product Code 5422141
- Overview
Smart styling meets definitive practicality with Burberry's Bankston holdall. Fastening with heritage-style buckled straps and a practical top zip, this generously sized bag is crafted in luxuriously soft grainy leather and trimmed with signature House Check canvas inserts. Complete with both top handles and shoulder straps, a handy outside pocket keeps travel documents to hand.
- Details
- Colour: Grey
- 2 hinged top handles with popper fastening
- Detachable shoulder strap
- 2-way top zip fastening
- 2 buckle straps
- Metal logo plaque
- Exterior slip pocket with magdot fastening
- Interior zip pocket; 2 slip pockets
- House Check canvas twill inserts to sides
- Protective studs to base
- H31cm x W50cm x D15cm approx.
- Pure leather
- Presented with a Burberry dust bag
- Made in Italy
- Delivery & Returns
International Delivery Charges
If paying in another currency your delivery charge will be calculated at checkout.
Delivery Option Duration Price Standard Delivery 3-5 days, Monday-Friday only. £5.95 Next Day Delivery Next working day on all orders placed before 3pm, Mon-Sat only. £12 Saturday Delivery Saturday only on orders placed before Friday 3pm. £15.95 Delivery to Europe £20 Outside of Europe Click here for International Delivery Terms for overseas shipping. £25
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Saint LaurentSlim Raw Denim Jeans£300.00
PS By Paul SmithEmbossed Logo T-Shirt£64.95
BurberryCashmere Check Trim Jumper£350.00


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sponsored by
Ari Vidali
CEO and Founder of Envisage Technologies
Ari is involved in building next-generation training systems, cloud-based learning, records management, automation of high-liability training operations, and pervasive readiness technologies. He is a committee member of the National Congress for Secure Communities and an advisory board member of IADLEST. He has consulted for Federal Agencies, Homeland Security, Public Safety, Military, and Law Enforcement on technology, security, legally defensible records, compliance, and training.
These shades are made to shield your eyes while keeping you looking good on the job.
POLICE Magazine asked some of the officers of the Scottsdale (Ariz.) Police Department's Rapid Response Team to review and rate their riot apparel, footwear, and turtle gear.
Preserve your eyesight with glasses designed to meet the needs of law enforcement. View this gallery for six currently available choices from leading law enforcement suppliers.
Buying holiday gifts for cops can be a difficult task. That's why the editors of Police Magazine are offering this quick guide to some of the best products that we've seen this year (or in the last few years) that sell for less than $200. This guide does not include any holsters because that's best left to the officer.
POLICE Magazine reviews the Smith Optics Aegis Eye Shields, Brite-Strike Traffic and Cycle LED Gloves, Magnum Spider Urban Boots, and 5.11 Tactical's Tac Dry Rain Shell.
Our eyewear product roundup includes seven versatile models, each created with either tactical or ballistic specifications. Many of the products are ergonomically-designed and feature a variety of new features such as scratch resistance, ballistic lenses, UVA/UVB/UVC protection, climate control seals, and interchangeable accessories.


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I was passionate. I found something that I loved. I could be all alone in a big old skating rink and nobody could get near me and I didn't have to talk to anybody because of my shyness. It was great. I was in my fantasy world.
Tags: | Dorothy Hamill,Great,World,Me,
I think Princess Diana probably had the most famous haircut, or Farrah Fawcett or Jennifer Aniston.
Tags: | Dorothy Hamill,Haircut,Princess,Think,
It was very much like Norman Rockwell: small town America. We walked to school or rode our bikes, stopped at the penny candy store on the way home from school, skated on the pond.
Tags: | Dorothy Hamill,America,School,Small,
I always had short hair, and I hated my short hair. I was always mistaken for a boy, but my mom wouldn't let me change my hair because she was always chasing me around with a hairbrush, and it was always tangled, so she just would cut it off, and she's right: short hair did suit me.
Tags: | Dorothy Hamill,Change,Hair,Me,
I always had the sense that nothing was never good enough - striving for perfection. My mother and I had a sort of typical mother-daughter relationship.
Tags: | Dorothy Hamill,Good,Mother,Perfection,
If you don't know a lot about figure skating, it's easy to fall in love with ice dancing because it's so romantic and so theatrical.
Tags: | Dorothy Hamill,Love,Fall,Easy,
In my teen years leading up to the Olympics, I loved having the excuse to skip out on parties because of skating. Partying wasn't my thing anyway. Mostly I hung out with other skaters. We were all buddies, so it's not like I missed out on socializing. I was really enjoying myself.
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Celebrate the Christmas season with these art and music activities for all ages. You'll find printables and lesson plans with instructions for creating Santa Claus, Christmas gifts and trees, ornaments, and more!
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As much as advice on drugs and therapy, patients need help with funds, tackling drug shortages and even a place to stay
A narrow tree-lined lane leads up to the Cancer Patients Aid Association tucked away inside the King George V Memorial compound, off a busy road in Mumbai.
The silent ambiance is misleading. It may look like any other administrative office, but step inside and you run into patients, sometimes children with their parents, looking for clarity on their cancer treatment and guidance to get their medicine at a lower price.
Conversations on cancer most often revolve around the high-cost of treatment and medicines, indeed a key worry. But people working with patients and experts watching the cancer drugs landscape say that attention should be also focused on other support features.
Trained people to administer newer medicines correctly to get the best results. And in no less measure, a place to stay for people travelling to big centres for treatment. Some of them end up staying on the pavements outside hospitals.
But none of this seems to be there anywhere on the radar of policy-makers. And the latest Union Budget has nothing to offer people living with cancer. Not surprising then, that CPAA's Mallika Narayan says matter-of-factly that Budget day was like any other day. A day spent working. The disappointment is palpable.
The government has to take a major role in healthcare for children, senior citizens and the general public, says Narayan. After all, they are collecting taxes from the people, she adds.
There are medicine shortages, people do not have money to buy medicines, they don't have places to stay when they come for treatment, she says. There are people willing to set up 'dharmshalas' for cancer patients to stay in the city, but the government needs to help with the land and see it is not misused, she points out.
The CPPA gets 150-200 cancer-related calls every day, says Vinaya Chacko, Executive Director. "We try and give some type of assistance to everyone who comes to the Centre. No one is turned away," she says. But the difficult part is that patients need "quick help", she adds, mentioning the specific case of bone marrow transplants. A procedure for those with blood cancer, the cost (about Rs. 20 lakh) puts it beyond some patients in India.
More than just price?
But access evidently has more layers to it. An IMS Institute for Healthcare Informatics study in June 2016 points out that "patients in only six countries had access to at least half of the 49 new oncology medicines launched in 2010 to 2014." India got only seven of those drugs.
Murray Aitken, Senior Vice-President and Executive Director, QuintilesIMS Institute, explains the why. Different health systems are in different stages of development and maturity, he says. And, in India, there are broader issues around cancer care — diagnosis, treatment, the number of cancer specialists in the country and so on. Funding, be it out of pocket, through insurance or reimbursements, is only part of the problem.
"Even if there is access to the medicine, are they going to be used in the right way," he asks, pointing to genomic testing, biomarkers in patients and the ability to assess if a new drug works effectively in a patient. Aitken stresses the need for trained clinical staff and infrastructure. There are centres in India capable of handling high-end testing and treatment, but the widespread use of new therapies will have to navigate these issues, besides the concerns on payments and patents, he explains.
Tata Memorial Centre Director RA Badwe says that the need is to optimise the delivery of care in common cancers and build the human resource in uncommon cancers.
Meanwhile, the global cost of treating cancer grossed $107 billion in 2015, an 11.5 per cent increase from the previous year. Naturally, payers are seeking more assurances that treatments get the desired outcome, observes the study, adding that this tension is set to continue. Clearly a worrisome reality and reason enough for India to pull together a much more layered approach to make a difference in the lives of people with cancer.


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Doctor insights on:
Actos And Bladder Cancer
Is what they are saying about actos (pioglitazone) causing bladder cancer true?
Possibly: There is evidence of an excess number of cases of bladder cancer in patients who have taken the drug Actos (pioglitazone) compared to what might normally be expected in a large group of people. Epidemiologic research in this regard continues, but it may be prudent for those who have taken the drug for longer than 1 year to be screened for this, especially in patients with other risk factors such as smoking. ...Read moreSee 1 more doctor answer
Cancer (Definition)
Cancer is a group of diseases that is characterized by uncontrolled cell growth leading to invasion of surrounding tissues that spread to other parts of the body. Cancer can begin anywhere in the body and is usually related to one or more genetic mutations that allow normal cells to become malignant by interfering with internal cellular control mechanisms, such as programmed cell death or by preventing ...Read more
Why is actos (pioglitazone) still on market although it's confirmed to cause bladder cancer?
Not conclusive: There is not confirmation that it causes bladder cancer. The study you are mentioning was done in france where there is a very high percentage of smokers. Smoking can increase the level of bladder cancer. Kaiser is currently doing a large study to see if there is any association. Most of us still use Actos (pioglitazone) with our patients. Diabetes can be a bad disease also. ...Read more
I take 30 mg of actos (pioglitazone) for type 2 diabetes daily. It has been linked to increased risk of bladder cancer in person taking actos (pioglitazone). Is actors safe?
See answer: There has been a slight excess of bladder cancers detected in patients who have taken Actos (pioglitazone) compared to others who do not. This appears to be time and dose dependent. Very few people who take Actos (pioglitazone) will develop bladder cancer. However there are many alternatives so it makes sense to switch to another drug if that will be effective , . ...Read more
What are symtoms of bladder cancer? I had some bleeding, under ware stained been checked for infections don't have any vd, had my insides taken out years ago, burning iching lower pain, have taken the med actos, (pioglitazone)
Hematuria: While blood in the urine needs to be worked up by a urologist, Actos (pioglitazone) has not been convincingly associated with bladder cancer. You should see a urologist for evaluation. ...Read moreSee 1 more doctor answer
Is bladder cancer serious?
Yes: Most bladder cancers diagnosed in the us are, however, very early in their presentations (stages 0 or 1), and therefore curable. However, a neglected bladder cancer will progress to a more advanced form of cancer that may become incurable and lethal. Therefore, it is important to take care of this as soon as possible. ...Read moreSee 2 more doctor answers
Is bladder cancer painful?
Maybe: Bladder cancer is generally not painful until it has spread to local organs and structures. If it contained to the superficial lining of the bladder without invasion, it is usually not painful. ...Read moreSee 1 more doctor answer
Is bladder cancer hereditary?
No: Tobacco and environmental exposures to dyes for urothelial cancer; schistosoma hematobium, a parasite in egypt and chronic csatheterization for squamous cancr, and adenocarcinoma related to remnants of the urachus, the foetal conduit of urinary exretion through umbilicus into placental circulation...In this last case one might say "inborn error" but not genetic or hereditary. ...Read moreSee 1 more doctor answer
How serious is bladder cancer?
Serious: One can die from bladder cancer if that helps you understand it's gravity. The most common risk factor for bladder cancer is smoking. Do not smoke! ...Read moreSee 1 more doctor answer
Can you die from bladder cancer?
Yes: Bladder cancer can invade from the lining into the muscle and deeper. From that point it can spread to pelvic lymph nodes or into the bloodstream. If it gets this far even with therapy with chemotherapy the disease may not be controlled and eventually kill the patient. ...Read moreSee 2 more doctor answers
How dangerous is bladder cancer?
Depends: There are various grades of bladder cancer to determine how aggressive the cancer is. Cancers that are very aggressive and multifocal tend to be much more dangerous than other types of bladder that are more similar to normal bladder cells. If these very aggressive tumors are not treated appropriately, they tend to metastasize and spread over time. Once this occurs, the long term prognosis is poor. ...Read moreSee 2 more doctor answers
Bladder (Definition)
The bladder is a muscular organ in the pelvis that accepts urine from the kidneys, stores the urine at low pressure, & expels the urine during voluntary voiding. Though seemingly a simple reservoir, the bladder is a complex organ intricately connected with the brain and spinal cord with sensory, motor, and autonomic circuits. The muscular layer that contracts during voids ...Read more
Bladder Cancer (Definition)
The bladder is the organ which holds urine. It may develop cancer as with any organ. There are two types: superficial bladder cancer and muscle invasive bladder cancer. The differences are important as they ...Read more


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Michelle Dixon, Stylist
Michelle enrolled in Maxine's in-house training program and has been a stylist for 14 years. Though she specializes in roller sets,rod sets, flat twist sets, styling, cutting, relaxing and texturizing ethnic hair, she is extremely versatile with all ethnic types and brings her experience with multi-cultural hair textures to updos. Michelle trained at the Vidal Sassoon Academy in Santa Monica, California, and at the Conservatory of Esthetics. She has participated in Art Institute fashion shows and makeovers for ABC7 and WGN, plus an episode of "Ambush Makeover" and several photo shoots and videos.
What is one special thing that everyone should know about Maxine Salon? It's professional, upscale and we help clients manage their busy schedules when booking appointments.
What has been your career high? I was mentioned in Chicago magazine for best multicultural hair.
What do you do in your free time? I love to Salsa dance.
What do you never leave home without? My eyebrows painted on.
Any celebrity clients? Any notable past gigs? Anika Noni Rose, Rachael Roy and Keshia Chante.
Favorite thing to do on a free Sunday? Go to church and spend time with family.
What is your biggest secret? I would love to try stand-up comedy.
What was the best decade for hair and why? The 30's. People really took the time to style their hair. Styles were classic, romantic and timeless.
What is the hair care product you cannot live without? Chronologiste Deep Nourishing Mask.
Michelle's haircuts are $105.00
5.0 Stars
From drab to Fab!
Michelle knows how to deal with my frizzy, curly hair! I has no idea what type if hair style would go with my face, but she gave me a cut that was cutting edge. I went from drab to Fab ! Even at 38.5 weeks pregnant, I am getting to my appointment-chauffeured- just so I can ensure I look good on baby's birth day! That's the power of Michelle at Maxine!
4.0 Stars
I would recommend Michelle
I am a curlie; course, shoulder-length, 3yr no-chemical treatment curlie girl. Naturally I was drawn to schedule an appointment with Michelle. I'd heard good things about her work with curlies, [as well as non-curlies]. I would recommend Michelle. Upon meeting her she was very welcoming, friendly, funny, and had an overall nice demeanor about her. When I first sat in the chair we of course went over what I wanted done, I sought her recommendations based on some of my goals. While she worked on my hair, she often checked on me. She explained some of the products she used on my hair, and their intended purpose. One of the products smelled really good, and I'm going to have to go back to the salon to indulge on that product. I was really happy with the cut I got; upon my next visit I would probably revisit styling options. Other staff members were funny, polite, and offered/served me tea and water. The overall atmosphere is really nice, and definitely coming in from outside, it was like a nice treat for myself. Some may not be prepared for the fee schedule though its a salon on Rush St, with really good customer service, really good products that they use on your hair, and many of the stylists are welcoming/funny. The fees you pay for service are worth the quality you get in return. The fees are listed on their website, so you can check them out there. I intend to go back [even after I buy that smell-good mystery product] for another appointment.
5.0 Stars
the best cut I ever had
I recently went to Maxine Salon and all I have to say is I walked out with the best cut I ever had. The vibe in the salon is fantastic and Michelle was nothing short of FABULOUS. I basically left it up to her to create a cut for me -- I didn't care what it was...I left it up to her. She created such an amazing cut and style for me -- I left the salon feeling like a new woman. She took the time to figure out what she was going to do and executed beyond measure. Everyone at the salon is so much fun but MICHELLE IS THE BOMB! She is such a sweet soul and great at what she does. I highly recommend this salon.


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How to dye easter eggs
Tip Sheet Credibility: 74
created by noryanna
Tip Sheet
|There's no need to buy expensive easter egg dye kits to color eggs. You can simply hard boil your eggs and then use regular food coloring in a half water, half vinegar solution. Add a little oil if you want to marble the eggs.
Tip Credibility: 74
submitted by noryanna
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