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The Epworth Project
Epworth / Blog
Missional Wisdom Attends Multiple UMC Annual Conferences
Over the past two months the Missional Wisdom Foundation staff has been hard at work networking at many of the United Methodist Church's Annual Conferences. We had representatives at the North Texas, Texas, Louisiana, and Wisconsin Annual Conferences. We sent great people like Maggie from the Ahadi Collective and Missional Wisdom Volunteer extordinar Bonni out to share our story to the conferences.
Our very own Elaine was the Plenary Speaker at both the Louisiana and the Wisconsin Annual Conferences. Many were deeply moved by Elaine's words as she spoke. Often times people in the audience would say "amen!" in unison and begin to clap after she said something generally awesome.
At both of the conferences that Elaine spoke at, our information tables were visited by many who had questions about our ministries, books, and of course Elaine.
We are so thankful for the opportunity to make new connections and to be working alongside the Church as a whole, to tend the new thing that is happening, and to bring about God's vision to the world together anew.
Pilgrimage is a journey to a place where an event of religious significance occurred or where objects of religious significance are housed. As a discipline to promote spiritual transformation, it is an ancient activity associated with many of the world's religions. In our efforts to train Christian leaders for the future, the Missional Wisdom Foundation embraces pilgrimage as an important avenue of spiritual formation.
Conversations with Elaine
Dr. Elaine Heath talks about how missional work is transforming what it means to be a Christian disciple.


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All About Eve [Deluxe Edition] [CD]
- Artist: All About Eve
- Release Date: 10/02/2015
Best Buy is dedicated to always offering the best value to our customers. We will match the price, at the time of purchase, on a Price Match Guarantee product if you find the same item at a lower price at a Designated Major Online Retailer or at a local retail competitor's store.Here's how:
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- Flowers in Our Hair
- Gypsy Dance
- In the Clouds
- Martha's Harbour
- Every Angel
- Shelter from the Rain
- She Moves Through the Fair
- Wild Hearted Woman
- Never Promise (Anyone Forever)
- What Kind of Fool
- In the Meadow
- Our Summer [Extended Version]
- Flowers in Our Hair [Extended Version]
- In the Clouds [Extended Version]
- Wild Hearted Woman [Extended Version]
- Every Angel [Extended Version]
- What Kind of Fool (Autumn Rhapsody)
- Our Summer
- Lady Moonlight
- Shelter from the Rain [B-Side Version]
- Flowers in Our Hair
- Paradise
- Devil Woman
- Calling Your Name
- Appletree Man
- Like Emily
- What Kind of Fool (Reprise)
- Every Angel [12" Version]
- Wild Flowers
- Candy Tree
- More Than This Hour
- Another Door
- In the Meadow
- Never Promise (Anyone Forever)
- What Kind of Fool
- Gold and Silver
- The Garden of Jane Delawney

subset: commoncrawl


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Morley's sin-binning when he came on as a substitute in the First Test last Friday was so clearly the difference between the two sides in a 17- 12 Kiwi win that it is undoubtedly a good idea for him to get it out of his system as soon as possible.
Morley asked to play from the beginning in the last midweek match of the tour and his coach, Phil Larder, has obliged.
"All the games I've had on tour have been as a substitute," said the 19-year-old Morley. "I want to play from the start and tried to force my way in for the Second Test.
"When the players came off after losing I couldn't look them in the eye because I felt I'd let them down, but they have been great about it.
"Phil has told me that he blames the sin-binning for us losing the match, but he doesn't blame me personally."
Larder has not been entirely satisfied with the form of Iestyn Harris, so he now comes under some pressure for his Test place from Karle Hammond, the St Helens utility player, who is given a chance to impress at stand- off.
Another Saints player, winger Joey Hayes, will be on his way home this week after failing a fitness test on his knee, his absence means Keith Senior plays on the wing and Tulsen Tollett at centre, with Nathan McAvoy, the Academy captain, borrowed in order to fill in on the bench.
Keighley's Jason Critchley will also fly home on Thursday for an operation on his cartilage and ligaments.
The senior side's opposition cannot be taken lightly, especially by tourists still looking for their first win in New Zealand. The Maori side features players with British experience in Tukere Barlow and Gavin Hill, and is captained by the former Sheffield, York and Castleford loose-forward, Tawere Nikau, who would surely be playing for the national side were it not for his feud with his one-time Castleford team-mate, Richie Blackmore.
Great Britain: Prescott (St Helens); Senior (Sheffield), Mather (Perth), Tollett (London), Roper (Warrington); Hammond (St Helens), Smith (Castleford); McDermott (Bradford), Lowes (Bradford, capt), Malloy (Featherstone), Morley (Leeds), Cassidy (Wigan), Dwyer (Bradford). Substitutes: Phillips (Warrington), Harmon (Leeds), Bradbury (Oldham), McAvoy (Salford).
NZ Maoris: Murray; Farrar, Henry, Tawa, Walker; Stevens, Howell; Rauhahi, Barlow, Hill, Pearce, Sturm, Nikau (capt). Substitutes: Ramsay, Gardiner, Milner, Whakarau.
- More about:
- Bradford
- Cycling
- Tourism
- Warrington


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Disclaimer - I don't own Harvest Moon
Chase looked at his pie triumphantly. "it is perfect" he thought to himself. It had taken him hours, but it was finally finished. He smiled to himself smugly as he lovingly placed it in the oven.
"Chase!" He heard Akari call to him from the dining room.
Chase walked out to find her, drying a pan as he went. He looked at the young farmer grinning at him. She handed him a recipe.
"Thank you so much for this!" she exclaimed "I have been racking my brain for ages over how to make this".
Chase shook his head "No need to thank me, it's the least I could do after you had given me that 'new' recipe".
Akari grinned at him with a glint in her eye. "You're cooking it now – aren't you?" she asked
He smiled, and nodded in agreement. "Yeah - though I've had a few problems. The filling is either to sweet or too sour..." He shook his head. He still hadn't worked out what he had done with the last pie to make it taste so awful. He could still taste it... Chase gave a little shudder.
Akari nodded. "I know, it took me ages to make it just right."
Chase smiled and crossed his arms triumphantly. "It's in the oven now. It should be ready in a minute – care for a taste? It's going to be great"
Akari smiled but shook her head. "No thanks, I just..." The words died on her lips. She sniffed the air. Her smile slowly faded. Glancing at Chase she frowned and asked "Is something burning?"
It's my first story, so was a bit scared about putting it up - hope you like it!


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Friday night marked the annual Picnic on The Stray for the WMG team.
Our friends from NetConstruct and Ingenuity Digital joined us for sunshine, food, drinks, cricket and giant Jenga on the huge grassy fields that those familiar with Harrogate will know as "The Stray".
The event kicked off at 5pm, with the teams descending on the Stray for after work drinks. The picnic got underway with people tucking into wraps, mini-bagels, vol-au-vent's and some deliciously-sweet mini puds. With Elderflower Pimms, bottles of beers, summer fruits ciders and G&T's, there was something for everyone.


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Condition Details
Style: 23694748 Color Code:
Vintage cream-colored suede top by Stephen Burrows. Zig zag scalloped edges throughout. Two front pockets. Suede tie front closure. Unlined.
Stephen Burrows is the first African American fashion designer to achieve international acclaim. He graduated from F.I.T. in 1966 and went on to design clothing that was comfortable, chic, and fashion-forward. His designs became a foundation for American style and was first sold at Henri Bendel in 1970. He was nominated for multiple Coty Awards throughout his early career.


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Jan 14, 2016 09:12 AM EST
Opioid like codeine and many others are often used to temporarily elevate someone's mood if they're feeling down. However, a new study said that with long-term use of such type of drug, the risk of acquiring depression is higher.
A team of researchers from Saint Louis University conducted a study regarding the effect of opioids to the body when it comes to long-term use. It showed that it may result to a condition called 'depression.'
The study, published on a site called Annals of Family Medicine a few days ago, started with the researchers analyzing gathered data of patients starting from year 2000 up to 2012. The researchers found out that all of the patients whose ages range from 18 to 80 are new opioid users that has no history of depression or other related cases prior to the start of the treatment.
According to the list of data they have gathered, out of the 107,755 patients recorded, 70,997 patients were from the Veterans Health Administration, or also known as VHA. 13,777 were from Baylor Scott & White Health, while the remaining 22,981 patients were from the Henry Ford Health System.
The researchers were able to figure out after looking through the entire records that once the opioid treatment ended, a lot of patients started showing signs of depression. 12 percent of the subjects from VHA have reported acquiring the condition, 9 percent from BSWH and 11 percent from HFHS, on the other hand, have experienced the onset stage of depression.
According to study lead author Jeffrey Scherrer, Ph.D., an associate professor in Family and Community Medicine at Saint Louis University, the results of the study among three groups were pretty consistent despite of the fact they have existed in three different healthcare systems that have their own patterns and demographics.
He also noted that the relation between episodes and the onset of depression has a lot to do with the long-term use, and not the possible dose that varies in each patient. Dr. Scherrer and his team also discovered that the use of such drug in 30 days affects the neuroanatomy of a person, thus imposing the risk of onset depression.


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text: Concours Correct Upper Power Steering Control Valve to Cylinder Hose for 1967-1969 Mustang and Cougar.This hose mirrors the original in every way with a natural silver finish. For retaining the original factory look, or just replacing worn hoses. This is the upper hose, see related parts for the lower cylinder to valve hose.Related Parts:-Cylinder to Valve Hose, Lower, Concours, #CSP25-Power Steering Hose Clamp, #GM23-Power Steering Hose Bracket, #7C510C-Power Steering Hose Insulator, #3A609B


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text: Love is what drives innovation, because it is what brings people together, makes them stretch beyond their usual comfort zones, and allows them to trust each other enough to take a chance and build something novel together. Love is particularly important when trust is low, when people are different, when barriers are high. Read it here.


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Jovian Ice CreamMature
Matt Slick, founder of CARM, the Christian Apologetics and Research Ministry, writes that, in a debate, the only logical argument that an atheist can use is "that it may be possible that there is no God" (Slick). He then goes on to compare the nonexistence of God to the existence of "an ice cream factory on Jupiter," indicating that there is an equal probability of both, and that one may as well argue against the existence of a Higher Power as argue for the existence of Jovian soft-serve.
This makes absolutely no sense to me. In my, admittedly biased, view, it is the other way around. When a equation is made between two opposite actions (in this case disbelief in God and belief in Ben and fucking Jovey's), it is a clear red flag for a false analogy. If we edit it a bit, so that belief=belief and disbelief=disbelief, however, we come out with a more logical comparison.
So, in my view, arguing that there is a God is more similar to arguing that there is an Iogan Dazs (sorry, couldn't resist) factory located upon the planet with the Great Red Spot that is arguing against the aforementioned's existence. But that's just my humble opinion, and I don't think I'll use it in a debate.
As one can tell, the question of "is there a God?" is more difficult to answer and prove than smaller religious considerations. I find it more fun to disprove little tidbits. Note: it may seem that I'm picking on Christianity excessively in this portion--that is not out of emnity for the followers of Jesus, but rather because it is the religion with which I am most familiar.
It's already been proven beyond any reasonable doubt that the world was not created 6000 years ago. No matter how long certain southern states try to teach their public school children that early humans lived in a world populated by dinosaurs, it is just not so (two words for you: carbon dating.) Also, it no longer seems likely that the world was created in six days, or that humans were originally created to reign over the earth (I mean, come on, we only showed up in relatively recent history). And evolution is real, dammit. That's why there are drug resistant diseases. One strain of pathogen can evolve into a completely different species in a matter of hours. Evolution is also why the little furball you call a "dog" and dress in sweaters does not eat you.
By the way, as Jupiter is named for the king of the Roman Gods, not the American ones, I would very much doubt that there is an ice cream factory there. It would simply not be allowed.
Gelato, now...that's a different story.
Per favore.


text: Code: http://www.imdb.com/title/tt0405629/ Rating: 6.9/10 Runtime: 92 min Language: France, Belgium Country: English, Finnish, French, German & Dutch (english subs included) Color: Black and White Director: Gustave de Kervern & Benoît Delépine Cast: Benoît Delépine ... L'employé Gustave de Kervern ... L'ouvrier agricole (as Gustave K/Vern) Michel de Gavre ... Le paysan Gérard Condejean ... Le Chinois Isabelle Delépine ... L'épouse Pierre Ghenassia ... Le patron Fred Martin ... Le collègue Jan Bucquoy ... L'amant Pierre Carles ... Le médecine Céline Normand ... Infirmière Description: Mr Vives is not fond of the lazy farmer's hand who keeps blocking the road with his large harvester, so he gets back at him, and the farmer's hand gets back at Mr Vives, and round and round it goes. Until one day, when this causes Mr Vives to lose his job and come back early to discover his wife in bed with another man. Furious, he drives up to the farm hand in the middle of a field and starts a fist fight which ends in the harvester. They wake up together at the hospital, both with useless legs. It seems they're doomed to stay together from now on. Code: http://rapidshare.com/files/156912491/Aaltra.part1.rar http://rapidshare.com/files/156916636/Aaltra.part2.rar http://rapidshare.com/files/156921082/Aaltra.part3.rar http://rapidshare.com/files/156925565/Aaltra.part4.rar http://rapidshare.com/files/156929803/Aaltra.part5.rar http://rapidshare.com/files/156934040/Aaltra.part6.rar http://rapidshare.com/files/156937724/Aaltra.part7.rar http://rapidshare.com/files/156938259/Aaltra.part8.rar Rar Password: None


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4 April 2013 – Singapore: ONE Fighting Championship™ (ONE FC) announced today that all fighters have made weight and are ready for ONE FC: KINGS & CHAMPIONS which takes place tomorrow evening at Singapore Indoor Stadium. The entire card, which is headlined by a ONE FC Lightweight World Championship bout between Kotetsu "No Face" Boku and Shinya "Tobikan Judan" Aoki, will also be available live on Pay-Per-View at www.onefc.livesport.tv.
Visit the official ONE FC: KINGS & CHAMPIONS weigh-in photo gallery by clicking:
Kotetsu Boku (70kg/ 154lbs) VS Shinya Aoki (70.1kg/155lbs)
Brock Larson (83.9kg/ 185lbs) VS Melvin Manhoef (83.9kg/185lbs)
Jens Pulver (60.9kg/ 134lbs) VS Masakatsu Ueda (61kg/135lbs)
Thanh Vu (61kg/ 135lbs) VS Kevin Belingon (61.1kg/135lbs)
Arnaud Lepont (69.9kg/154lbs) VS Eddie Ng (69.9kg/154lbs)
Yusup Saddulaev (61.1kg/ 135lbs) VS Leandro Issa (61.1kg/ 135lbs)
Rene Catalan (56.1kg/ 124lbs) VS Alex Silva (56.5kg/ 125lbs)
Bashir Ahmad (65.7kg/ 145lbs) VS Shannon Wiratchai (65.8kg/ 145lbs)
Swain Cangco (92kg/ 203lbs) VS Jake Butler (92.9kg/ 205lbs)
Chen Yun Ting (56.3kg/124lbs) VS Ronald Low (56.4kg/124lbs)
Fans from around the world can witness the action online via live streaming at www.onefc.livesport.tv. The first two undercard fights are available for viewing free-of-charge and the main card fights will be available for purchase at just US$9.99.
Tickets for ONE FC: KINGS & CHAMPIONS are now on sale at SISTIC (www.SISTIC.com.sg). Tickets categories begin with the full Red Carpet and cage-side experience for VIPs at $S348 followed by Arena – $S148, Terrace – $S68 and Balcony – $S38. All applicable service charges apply.
For more updates on ONE Fighting Championship™, please visit www.onefc.com and follow on Twitter @ONEFCMMA and Facebook atwww.facebook.com/ONEFCMMA.
About ONE Fighting Championship™
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Job Summary
- Salary: Undisclosed
- Work Type: Permanent / Full Time
- Min. Education Level: Diploma
- Field of Study: Building, Construction
- Skills: Sales, Product marketing, Business development
Job Descriptions
We are part of an expanding Taiwanese group of companies with more than 20 years business activities in the South East Asia region. Our regional operation headquaters is in Singapore and we have production facilities in Malaysia, Indonesia, Vietnam and Thailand.
Our business covers sealants, adhesives and chemicals for the industrial, commerical and consumer applications.
Currently, our organisation is expanding our business activities into water proofing membranes, floor coatings, adhesives, sealants and related products used in the building and construction industries in Malaysia. To support our growth plans, we are looking for a suitable candidate to be based in our office in Kuala Lumpur and Johore, Malaysia to fill the following position:
Job scope:
- Managing assigned product lines and its sales performance
- To lead and manage new product market entry and business development initiatives
- To support and assist country sales team to achieve expected results
- To develop, monitor and manage sales distribution networks
- To develop and grow direct key account business
- This position reports to both the Country Manager, Malaysia and the Regional General Manager, South East Asia
- At least a recognised technical degree or diploma related to building and construction
- Have several years of direct hands on experience in the building and construction trade
- Good commercial knowledge of the Malaysian markets
- Preferably has current working technical knowledge of products such as water proofing membranes, adhesives and sealants used in the building and construction trade
- Able to lead a sales team effectively
- Able to communicate in English. The ability to also communicate in Mandarin is an advantage
- Comfortable and can work well in a matrix organisation
- Preferably has several years experience working with distributors, wholesalers, dealers and end-users
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Watch Seirei no Moribito
You are viewing Episode list with English Subbed. Navigate the episode to watch the video..
Genres: adventure, Drama, Fantasy, Demons, Female bodyguard, Fugitives, Historical, Lone warrior,
Plot Summary:
Balsa the spearwoman is a wandering warrior, who takes on the task of saving lives, in atonement for a past sin. On her journey, she happens to save a prince, and is tasked with becoming his bodyguard. And he is going to need one, for his own father, the emperor, wants him dead. Balsa, the spear wielder and bodyguard, is visiting the New Yogo Empire. She is hired to protect the Second Prince, Chagum, who is endangered because he is possessed by a being despised by his father, the Emperor, who ordered his assasination. The two go on a perilous adventure for the survival of the prince. Throughout the story, Balsa's past will come to light and they will uncover mysteries about Chagum's condition while developing a family-like relationship with each other and others. Video:


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Delusions of grandeur.
Trip Start Sep 28, 2011
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I've slept little. My head and heart too troubled from another epic fail. I feel like I've got cotton wool wrapped around my face. And no; I don't really know what that's like either.
I manage to get my cards cancelled and begin the process of having new ones sent through. I don't think I'll be leaving San Juan any time soon. The voice on the end of the line cannot even humour me with a time frame, but I am informed that some little scumbag has used my credit card four times this morning. In Rivas. I'm guessing a local, most likely driving; two of the transactions were at a petrol station. He's possibly a regular in San Juan at the weekend, praying on young drunks. I'm betting he makes a killing.
I'm suddenly overtaken by wild delusions of grandeur. I'm going to track this guy down and cut his hands off. And then eat him. Actually that last part is a lie and just because I'm hungry. I'm also totally bemused as to how a dark skinned Latino man used my credit card with the name 'Stuart Andrew Jameson' on the front. I become aware my voice is raised and I'm taking it out on the Indian call centre guy. Eventually I come back to earth. And eat a taco. With cheese. And pork. Mmmmmmm.
Ok enough of this entry. I'm off to get a cheesy pork taco.


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Efficacy and Safety of Aflibercept and Its Role in the Treatment of Metastatic Colorectal Cancer
Vascular endothelial growth factor (VEGF) and related pathway elements are critically important in the pathogenesis, growth, and development of solid tumors. Inhibiting the VEGF signaling pathway is being investigated as a therapeutic strategy for cancer, either by blockade of VEGF ligand binding or inhibition of the VEGF receptor. Aflibercept is a VEGF inhibitor that has been approved by the US Food and Drug Administration for the treatment of macular degeneration and metastatic colorectal cancer (mCRC).
A search of PubMed and MEDLINE from January 2000 to August 2013 was performed using the following terms (or combination of terms): VEGF, colorectal cancer, mCRC, aflibercept, ziv-aflibercept. Studies were limited to those published in English.
Phase 1 and 2 clinical trials of aflibercept in advanced non-hematological cancer showed acceptable safety and provided justification for further investigation. Four phase 3 clinical trials were conducted to evaluate aflibercept for the treatment of different cancers. The VELOUR trial evaluated aflibercept with FOLFIRI in patients with mCRC. The addition of aflibercept resulted in improved median overall survival (OS, 13.5 vs. 12.1 months, p = 0.0032). The VITAL trial evaluated docetaxel plus aflibercept vs. docetaxel plus placebo in patients with non-small cell lung cancer (NSCLC) who had progressed after first-line platinum-based chemotherapy; there was no significant difference between the two treatment groups in terms of OS. The VANILLA trial in patients with metastatic pancreatic adenocarcinoma was terminated because addition of aflibercept to gemcitabine failed to demonstrate improved OS in an interim analysis. In patients with metastatic androgen-independent prostate cancer, the VENICE trial also failed to demonstrate an increase in OS when aflibercept was combined with standard first-line chemotherapy. The most common adverse events associated with aflibercept in these trials were hypertension, venous and arterial thromboembolic events, hemorrhage, and proteinuria.
In patients with mCRC, aflibercept demonstrated an improvement in OS when added to FOLFIRI. However, it has failed to show similar benefits in other tumor types. Further investigation is needed to improve patient selection and to distinguish patients who may benefit best from aflibercept from those who will require other anti-angiogenic agents.
KeywordsAdverse events Aflibercept Colorectal cancer Tumor angiogenesis Vascular endothelial growth factor
Therapeutic options for patients with cancer, such as melanoma, prostate cancer, and renal cell carcinoma, have increased during the past decade because of improved understanding of tumor biology and availability of targeted agents. Vascular endothelial growth factor (VEGF) and related signaling pathways are considered critically important in the pathogenesis, growth, and development of cancer. Inhibiting the VEGF signaling pathway has been investigated as a therapeutic strategy for cancer, either by blockade of VEGF ligand binding or inhibition of the VEGF receptor (VEGFR) [1].
Vascular Endothelial Growth Factor
A prevailing hypothesis is that when a tumor outgrows its blood supply, the resulting hypoxia switches on hypoxia inducible factor (HIF) α signaling that stimulates the production of several pro-angiogenic factors [1, 2]. An important pro-angiogenic pathway is that mediated by the VEGF family of ligands, which includes six growth factors [VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, and placental growth factor (PlGF)] and three VEGF receptors [2, 3, 4]. The VEGFRs are transmembrane tyrosine kinases present mainly in endothelial cells. When circulating VEGFs bind to VEGFRs, signal transduction pathways are activated that may promote endothelial cell proliferation, differentiation, migration, and angiogenesis [3]. The VEGF/VEGFR signaling pathway is involved in normal developmental and wound healing processes such as embryologic development, skeletal growth, and wound healing [4].
In addition, it has been shown that tumor angiogenesis is usually 'dysfunctional', with profound alterations, in terms of shape, size, and permeability, as compared to normal angiogenesis [5]. Anti-angiogenic treatments may lead to, not only inhibition of angiogenesis, but also normalization of such abnormal vasculature, allowing, for example, better extravasation of anticancer drugs in tissues. Such a phenomenon appears to be critical in colorectal cancer (CRC), where indeed anti-angiogenic treatments, such as bevacizumab, are commonly administered in an adjunction to cytotoxic chemotherapy [5].
Furthermore, VEGF expression in CRC may be associated with metastasis, recurrence, and poor prognosis [6, 7, 8]. Therefore, inhibitors of VEGF or VEGFRs were developed to treat malignancies by limiting tumor angiogenesis associated with activated VEGF/VEGFR pathways. Here, we review the rationale and clinical development of aflibercept for the treatment of cancer with particular emphasis on its use in CRC.
A search of PubMed and MEDLINE from January 2000 to August 2013 was performed using the following terms (or combination of terms): VEGF, colorectal cancer, metastatic colorectal cancer (mCRC), aflibercept, ziv-aflibercept. Studies were limited to those published in English.
We also reviewed reference lists and discussed search results with experts. Due to its novel nature, abstracts or presentations of any national or international conference on aflibercept were assessed for inclusion.
Vegf-Binding Agents
Aflibercept (VEGF Trap)
Some tumors may become resistant to anti-VEGF therapies because of an increase in the levels of PlGF [13]; therefore, it is feasible that the binding of aflibercept to PlGF could be of interest because by binding or "trapping" both VEGF and PlGF aflibercept could possibly overcome the development of resistance to other drugs such as bevacizumab [14]. In preclinical studies, aflibercept prevented the growth of micrometastases, caused regression and renormalization of vasculature in existing tumors, and inhibited new vascular growth [15, 16].
Aflibercept: Preclinical Data
Aflibercept inhibits VEGF-induced phosphorylation of VEGFR-2 in human umbilical vein endothelial cells and VEGF-induced fibroblast proliferation in vitro [13]. In mice, aflibercept induces regression of capillaries, cessation of blood flow, and apoptosis of endothelial cells, and empty basement membrane sleeves [17, 18]. Several studies of the effect of aflibercept on tumor xenografts, including neuroblastoma, Wilms' tumor, ovarian cancer, pancreatic tumors, renal cell carcinoma, glioma, and CRC, have reported anti-angiogenic activity, including regression of blood vessels, decreased tumor vessel density and perfusion, inhibition of metastases, and improved survival [19]. Inhibition of tumor growth and improved survival were demonstrated for several animal tumor xenografts when aflibercept was administered with trastuzumab, docetaxel, paclitaxel, irinotecan, 5-fluorouracil, or radiotherapy [20, 21, 22, 23, 24, 25].
Clinical Data
Phase 1 Trials
Phase 1 clinical trials of aflibercept in patients with cancer
No. of patients
Aflibercept dosage/schedule
Drugs given with aflibercept†
Dose-limiting toxicities‡
Common adverse events
Recommended phase 2 dosage of aflibercept (+combination drugs)
Freyer et al. [26]
4.0, 5.0, or 6.0 mg/kg IV every 3 weeks
Febrile neutropenia
6 mg/kg every 3 weeks + docetaxel and cisplatin
Moderate epistaxis
Isambert et al. [27]
2.0–9.0 mg/kg IV every 3 weeks
Neutropenic infection (2.0 mg/kg)
6.0 mg/kg every 3 weeks + docetaxel
Dysphonia (7.0 mg/kg)
Uncontrolled hypertension (9.0 mg/kg)
Limentani et al. [28]
2.0, 4.0, or 5.0 mg/kg IV every 2 weeks
4 mg/kg every 2 weeks + FOLFOX4
Patnaik et al. [29]
4.0 or 6.0 mg/kg IV every 2 weeks
Gemcitabine weekly
4 mg/kg every 2 weeks + gemcitabine weekly
Pulmonary embolus
Van Cutsem et al. [30]
2.0–6.0 mg/kg IV every 2 weeks
Proteinuria (4.0 mg/kg)
4.0 mg/kg every 2 weeks + I-LV5FU2
Moderate epistaxis
Stomatitis (5.0 mg/kg)
Febrile neutropenia (6.0 mg/kg)
Kuhnowski et al. [31]
3 or 6 mg/kg IV every 3 weeks
6 mg/kg every 3 weeks + R-CHOP
Arthralgia (grade 3)
Febrile neutropenia
Asthenia (6 mg/kg)
Tew et al. [32]
1.6 mg/kg/week SQ (max dosage)
0.8 mg/kg/week
Hypertension (0.8 mg/kg/week)
Lockhart et al. [33]
0.3–7.0 mg/kg IV every 2 weeks
4.0 mg/kg every 2 weeks
Rectal ulceration (7 mg/kg)
Diaz-Padilla et al. [34]
2.0–6.0 mg/kg IV every 3 weeks
6 mg/kg every 3 weeks + pemetrexed and cisplatin
Pulmonary embolism
Deep vein thrombosis
In another trial evaluating the safety and efficacy of aflibercept, the agent was administered intravenously in doses ranging from 0.3 to 7.0 mg/kg every 2 weeks in 47 patients with refractory solid tumors or non-Hodgkin's lymphoma [33]. A partial response [PR, defined by response evaluation criteria in solid tumors (RECIST) criteria] [35] was observed in three patients, and two patients had stable disease (SD). The most common toxicities observed were fatigue (63.8%), nausea (36.2%), and vomiting (27.7%); grade 3 hypertension occurred (16.7% patients at the 2.0 mg/kg dose; 42.9% patients at the 4.0 mg/kg dose; 75.0% patients at the 5.0 mg/kg dose) and grade 3 proteinuria was reported (1 patient, 7.0 mg/kg dose) (Table 1).
Phase 2 Trials
Phase 2 clinical trials of aflibercept in patients with cancer
No. of patients
Aflibercept dosage/schedule
Drugs given with aflibercept
Primary endpoint
Adverse events
Massarelli et al. [36]
Lung adenocarcinoma (resistant to platinum and erlotinib)
4 mg/kg intravenous every 2 weeks
Grade 3–4: dyspnea, hypertension, non-cardiac chest pain, fatigue
Tew et al. [37]
Recurrent platinum-resistant epithelial ovarian cancer
2 or 4 mg/kg intravenous every 2 weeks
Grade 3–4: hypertension proteinuria, encephalopathy, renal failure
Colombo et al. [38]
Advanced epithelial ovarian cancer with ascites
4 mg/kg intravenous every 2 weeks
RPRR = doubling time to 1st paracentesis
Median time to repeat paracentesis = 76 days
Grade 3–4: bowel obstruction, nausea, vomiting, anorexia, edema
10/16 patients (62.5%) achieved RPRR
Median PFS 59.5 days
Tang et al. [39]
Metastatic colorectal cancer
4 mg/kg intravenous every 2 weeks in two patient groups
RR and 4-month PFS
Prior BEV (n = 27): 1 PR, DCR, 30%; median PFS 2.4 months; median OS 8.5 months
Grade 3: fatigue (78%), hypertension (55%), proteinuria (49%), headache (43%)
Prior BEV: 51 patients
No prior BEV: 24 patients
Patients without BEV treatment (n = 24): DCR, 29%; median PFS 2.0 months; median OS 10.4 months
Tarhini et al. [40]
Melanoma (inoperable stage III or IV; cutaneous or ocular origin)
4 mg/kg intravenous every 2 weeks
RR and 4-month PFS
1 CR, 8 patients 4-month PFS
Grade 3/4: hypertension, proteinuria, extraocular muscle paresis, renal failure
Mackay et al. [41]
Gynecologic soft tissue sarcomas (recurrent or metastatic)
4 mg/kg intravenous every 2 weeks
RR and prolonged stable disease
Median OS: leiomyosarcoma 15.1 months; carcinosarcoma 3.1 months
Grade 3: hypertension, fatigue, lymphopenia
Sherman et al. [42]
Thyroid cancer (radioactive iodine-refractory, PET positive carcinoma)
4 mg/kg intravenous every 2 weeks
RR and 6-month PFS
10 of 18 patients with stable disease remained on study >6 months (3 of 18 patients on study >12 months)
Grade 4: proteinuria, thrombotic microangiography, lymphopenia, confusion, myocardial infarction
Median duration 178 days
Twardowski et al. [43]
Metastatic urothelial cancer
4 mg/kg intravenous every 2 weeks
RR and PFS
Grade 3: fatigue, hypertension, proteinuria, pulmonary hemorrhage, pain, hyponatremia
Median PFS 2.79 months
Metastatic colorectal cancer (no previous treatment)
4 mg/kg every 2 weeks
12-month PFS
12-month PFS = 25.8% (95% CI 17.2–34.3) vs. 21.2% (95% CI 12.2–30.3)
Grade 3/4: hypertension (53.4% vs. 6.9%), proteinuria
ORR 49.1% vs. 45.9%; p < 0.001
Median PFS 8.48 vs. 8.77 months
Aflibercept was evaluated in two major phase 2 clinical trials for the treatment of mCRC [39, 44]. The first of these studies was a two-stage, multicenter, open-label, trial in 75 patients who had received prior treatment for the disease (Table 2) [39]. Patients were categorized into two groups dependent on previous treatment (prior bevacizumab, 51 patients; no prior bevacizumab, 24 patients), and all patients received aflibercept (4 mg/kg) intravenously every 2 weeks. After aflibercept treatment, the disease control rate (DCR, PR plus SD) and median PFS were similar in both groups (Table 2). AEs were common (Table 2). The authors concluded that aflibercept had modest activity against refractory or relapsed mCRC, regardless of prior therapy with bevacizumab.
The second major phase 2 trial was the AFFIRM trial which was a randomized open-label trial evaluating the safety and efficacy of aflibercept and mFOLFOX6 (5-fluorouracil, leucovorin, oxaliplatin) as first-line treatment for mCRC [44]. Patients (n = 236) were randomized to aflibercept (4 mg/kg) plus mFOLFOX6 or mFOLFOX6 alone every 2 weeks (Table 2). Mean 12-month progression-free survival (PFS) was 25.8% for aflibercept plus mFOLFOX6 and 21.2% for mFOLFOX6 alone (Table 2). Addition of aflibercept to mFOLFOX6 significantly increased the objective response rate (ORR, 49.1% vs. 45.9%, p < 0.001); however, median PFS was similar with or without aflibercept, and patients who received aflibercept had a higher frequency (53.4% vs. 6.9%) of grade 3/4 hypertension (Table 2).
Phase 3 Trials
Phase 3 clinical trials of aflibercept in patients with cancer
Clinical trial name
No. of patients
Aflibercept dosage/schedule
Drugs given with aflibercept
Response frequency (aflibercept vs. placebo)
Median PFS (month) (aflibercept vs. Placebo)
Median OS (month) (aflibercept vs. placebo)
Metastatic colorectal cancer
4 mg/kg intravenous every 2 weeks
FOLFIRI aflibercept
PR 19.8 vs. 10.8
6.9 vs. 4.7 (HR 0.758; p < 0.001)
13.5 vs. 12.1 (HR 0.817; p = 0.0032)
CR 0 vs. 0.4
Non-small cell lung cancer
6 mg/kg intravenous every 3 weeks
Docetaxel aflibercept
PR 23.0 vs. 8.6
5.2 vs. 4.1 (HR 0.82; p = 0.0035)
10.1 vs. 10.4 (HR 1.01; p = 0.90)
CR 0.2 vs. 0.2
Metastatic pancreatic adenocarcinoma
4 mg/kg intravenous every 2 weeks
Gemcitabine aflibercept
Not performed
3.7 vs. 3.7 (HR 1.02)
6.5 vs. 7.8 (early termination) (HR 1.16)
First-line chemotherapy after failing on androgen therapy
Metastatic castration-resistant prostate cancer
6 mg/kg intravenous every 3 weeks
Docetaxel/prednisone aflibercept
PSA response 68.6 vs. 63.5 (p = 0.075)
6.9 vs. 6.2 (HR 0.94; p = 0.31)
22.1 vs. 21.2 (HR 0.94; p = 0.38)
Bevacizumab and aflibercept treatment outcomes in patients with metastatic colorectal cancer
Outcome parameter
ML18147 [48] (n = 820) (BEV vs. placebo)
BEBYP [49] (n = 184) (BEV vs. placebo)
VELOUR [45] (n = 1,226) (aflibercept vs. placebo)
Second-line regimen
FOLFOX/FOLFIRI/CAPOX/CAPIRI ± bevacizumab
FOLFOX/FOLFIRI ± bevacizumab
FOLFIRI ± aflibercept
Response rate (%)
0.4 vs. 0
5 vs. 3
10.8 vs. 19.8
63 vs. 50
64.9 vs. 65.9
Disease control rate (CR + PR + SD)
22 vs. 35
21.5 vs. 10.4
Progression-free survival (month)
5.7 vs. 4.1 (1.6 absolute difference) (HR 0.63; p < 0.0001)
6.8 vs. 5.0 (1.8 absolute difference) (HR 0.65; p = 0.0062)
4.8 vs. 6.9 (HR 0.758; p < 0.001)
OS (month)
11.2 vs. 9.8 (HR 0.81; p = 0.0062)
12.1 vs. 13.5 (HR 0.817; p = 0.0032)
In the ML18147 study, patients, depending on the first-line therapy, received either oxaliplatin-based or irinotecan-based second-line chemotherapy. Median PFS was 5.7 vs. 4.1 months (p < 0.0001) and median OS was 11.2 vs. 9.8 months (p = 0.0062) in favor of the bevacizumab group [48]. The BEBYP trial was a phase 3 study that randomized patients with unresectable mCRC treated with bevacizumab plus first-line chemotherapy (fluoropyrimidine, FOLFIRI, FOLFOX or FOLFOXIRI) to receive a second-line chemotherapy with FOLFOX or FOLFIRI (depending on first-line chemotherapy) alone or in combination with bevacizumab at 5 mg/kg intravenously every 2 weeks. The study demonstrated an increased PFS by continuing bevacizumab in second-line (median PFS was 6.8 vs. 5.0 months, p = 0.0062) [49].
VITAL Trial
The VITAL trial was the second large randomized phase 3 trial to evaluate the efficacy and safety of aflibercept [12]. This was a double-blind, placebo-controlled study of aflibercept as second-line treatment for patients (n = 913) with NSCLC who had progressed after first-line platinum-based therapy (Table 3). OS was the primary endpoint. Patients received docetaxel plus aflibercept or docetaxel plus placebo. No difference was observed between the two treatment groups in terms of OS (median OS 10.1 vs. 10.4 months with/without aflibercept, respectively; HR 1.01; p = 0.90) (Table 3). Median PFS was slightly prolonged in the aflibercept group (5.2 vs. 4.1 months; HR 0.82; p = 0.0035). ORR was also higher in patients who were treated with docetaxel plus aflibercept compared with patients treated with docetaxel plus placebo (23.2% vs. 8.8%; p = 0.001).
VANILLA and VENICE Trials
The remaining two phase 3 clinical trials of aflibercept were conducted in a first-line setting and in combination with chemotherapy. The VANILLA trial enrolled patients with metastatic pancreatic adenocarcinoma, while the VENICE trial assessed patients with metastatic castration-resistant prostate cancer [46, 47]. The VANILLA trial was terminated early because of an estimation of decreased survival in patients who received aflibercept vs. control patients (Table 3) [46]. The VENICE trial sought to discover an added benefit for the use of aflibercept in patients with metastatic androgen-independent prostate cancer [47]. The primary endpoint of the study was OS. A total of 1,224 patients were enrolled. Patients were randomized into 1:1 ratio to receive docetaxel/prednisone plus aflibercept or docetaxel/prednisone plus placebo. There was no statistically significant difference in OS between both groups (median OS 22.1 vs. 21.2 months, p = 0.38; respectively); nor in PFS (6.9 vs. 6.2 months, respectively; p = 0.31). However, patients in the aflibercept arm experienced a higher incidence of grade 3/4 AEs (76.9% vs. 48.5%) which led to discontinuation rates of 43.9% for aflibercept vs. 20.9% in the placebo arm.
Aflibercept: Adverse Events
Adverse reactions to aflibercept were common in phase 1 and 2 trials (Tables 1, 2). In the phase 3 VELOUR trial, the tolerability profile for aflibercept plus FOLFIRI was consistent with that reported previously for aflibercept, FOLFIRI, and other anti-VEGF therapies. Aflibercept was associated with hypertension (19.1%), proteinuria (7.9%), and other common chemotherapy-related AEs such as diarrhea, hand-foot syndrome, and neutropenia [45]. In the phase 3 VITAL trial, patients who received aflibercept experienced a higher frequency of grade 3/4 AEs including neutropenia (aflibercept 28.0%, control 21.1%); fatigue (aflibercept 11.1%, control 4.2%); stomatitis (aflibercept 8.8%, control 0.7%) and hypertension (aflibercept 7.3%, control 0.9%) [12].
In the VELOUR trial, the incidence of treatment-related AEs was similar among patients who received aflibercept with prior bevacizumab exposure (AEs, 100% of patients) or no prior bevacizumab exposure (AEs, 98.9% of patients). In the aflibercept component of the study, the frequency of grade 3/4 AEs was similar between patients who had received prior bevacizumab (82.5%) and patients who had no prior bevacizumab experience (83.9%) [45]. In both groups, 25% of aflibercept-treated patients discontinued treatment because of AEs. The most frequent AEs common to aflibercept and bevacizumab were grade 3/4 neutropenia, diarrhea, asthenia, infections, and stomatitis; however, bevacizumab had a more favorable safety profile with less proteinuria and almost no gastrointestinal or constitutional toxicity.
Adverse events associated with aflibercept in the treatment of cancer
Adverse event (grade > 3)
Aflibercept (n = 1,333)
Placebo (n = 1,329)
Venous thromboembolic events
Arterial thromboembolic events
Gastrointestinal perforation
Cardiac dysfunction
Impaired wound healing
Despite extensive efforts, researchers have yet to identify a reliable and reproducible biomarker that allows selection and identification of patients who are most likely to benefit from aflibercept therapy. Circulating biomarkers are currently under evaluation as potential tools to monitor treatment response to anti-VEGF drugs. For some cancers, response to treatment with aflibercept may be monitored by measuring levels of cytokines, growth factors, and myeloid biomarkers. In patients with glioblastoma, treatment with aflibercept was associated with decreased levels of VEGF and PlGF [51]. Lower levels of growth-regulated oncogene α, hepatocyte growth factor, and stem cell growth factor β, and higher levels of free VEGF, were also associated with a PR in this patient group. Elevated baseline levels of CTACK/CCL27, MCP3/CCL7, MIF, and IP-10/CXCL10, and a decrease in VEGFR1-positive monocytes from baseline to 24-h post-aflibercept administration, have also been associated with improved response in glioblastoma patients [52].
Discussion and Future Directions
Over the last decade there have been unprecedented advances in the treatment of mCRC. In the modern era, the average median survival duration has doubled, and patients usually live longer than 2 years largely due to the availability of new active agents. Last year alone in 2012, the FDA has approved two new drugs, aflibercept and regorafenib, for the treatment of mCRC due to demonstrated overall survival benefits.
Although, as shown in this review, aflibercept has demonstrated overall survival benefits when combined to FOLFIRI for the treatment of patients with mCRC that is resistant to or has progressed following an oxaliplatin-containing regimen, due to the lack of head to head trials, its place in the treatment paradigm of mCRC, with the availability of similar agents such as bevacizumab, is still not well defined. Similarly, the best way to combine and sequence all of these drugs to optimize treatment has not yet been established. In some cases, predictive biomarkers can influence the choice of treatment. For instance, patients who harbor a K-ras mutation may benefit from strategies targeting the EGFR [53]. Despite extensive research, there are no reliable or reproducible markers that predict response to anti-angiogenic therapy. These advances in therapy have not only resulted in nearly doubling of the median overall survival, but have also resulted in many challenges and raised several questions such as: why such agents have modest clinical success despite the promising preclinical data? Which VEGF inhibitor is more potent and better tolerated? Can these inhibitors be used in combination and if so, can this type of treatment be sustained? What are the future promising agents targeting VEGF and related signaling pathway and strategies to combat mCRC? How do these new agents such as aflibercept compare directly to the older medications such as bevacizumab and how can we select the proper agent between the currently available drugs?
Additionally, the challenge is how to determine the optimal sequencing of these agents in treatment naïve patients, relapsed patients or in the maintenance setting. Lastly and perhaps most importantly, why aflibercept has failed to demonstrate similar benefits in other tumor types such as patients with NSCLC, prostate or pancreatic cancer and how we can improve patient selection and distinguish patients who may benefit best from aflibercept from those who will require other anti-angiogenic agents.
No funding or sponsorship was received for this study or publication of this article.
Conflict of interest
Dr. Salem and Dr. El-Refai declare no conflict of interest.
Compliance with ethics guidelines
This article does not contain any studies with human or animal subjects performed by any of the authors.
Open Access
This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.


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Viral mugshot - guy could wind up with modeling career
There's just something about a hunky bad boy that makes women forget common sense. Six-time convicted felon Jeremy Meeks caused quite a stir on the Stockton, California, Police Department's Facebook page when his mug shot was posted after he was arrested on felony weapons charges.
Jeremy's mug shot is so sexy it went viral – with nearly 70,000 likes and 20,000 comments, mostly from women totally enamored with the 30-year-old's baby blue eyes and chiseled jaw. Word travels fast over social media and comments like, "I would arrest him too ... hottest bad boy I've seen" and "Momma, I'm in love with a criminal" flooded the law enforcement site.
A spokesperson for the Stockton PD told a local news station that Jeremy is "one of the most violent criminals in the Stockton area," but even $900,000 bail isn't a deterrent for Jeremy's newfound fan base. With his sudden and swift internet fame, Jeremy Meeks might be able to leave his life of crime behind for a modeling gig, and if that doesn't work out for him, he certainly won't be hard up for dates after serving his time! (ABC News)


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Day 3 Thursday 22nd October
... Only need a hat if I come across one but NO more shopping I am done. Back in apartment catching up on all. Will venture out for a meal later and then early night as we have a 5 am start tomorrow and the tour is 12 hours. We have enjoyed the architecture along the way and the winding little streets with so much atmosphere. We have never seen so many eating places .The people are very helpful with the language barrier and the day has been ...
Day 168: Paris
... roundabout at the base of Arc de Triopmhe which seemed to have no method to it. Our next item to tick off the list was of course the Eiffel Tower. The Paris guide book pointed us in the right direction and made our way to the most identifiable and notorious building in Paris if not Europe. The tower looked exactly like it does in photos, which might sound silly but I didn't think it was all that exciting, but it is something that you have to see ...
Day 27 Paris, France
... the queue to 120 metres and gave it 15 minutes and did the Maths. According to us it was possible we could be the last ones in. So we waited and talked with the people around us on the line. To cut a long story moderately less long we made it and so did a handful of people behind us. It was very close. We cheered as we got it. It was 8pm when we emerged. We jumped on the metro and found a nice cafe close to our ...
Our last days in Paris
... get out is to nudge the one behind and in front at times, cars also park on corners, on pedestrian crossing, virtually, wherever they can fit. Not many hotels/taverns here, everyone goes to cafes and sit on the footpath, facing the road, in a line, buys a wine or beer, has a smoke and watches the passing parade and isn't there a lot happening to keep them entertained! The ladies are all wearing pretty summer dresses and are ...
Day 10: Paris
... very classy. They have a cafeteria on their top floor, so we had some lunch there. Then we went up on the roof, where you can look out over the city. You can buy coffee or an ice cream, there's artificial grass on the floor, and lounge chairs so you can relax, which a lot of people were doing as they enjoyed the sunshine. To finish our day we decided to do one complete loop on the bus. By this time it was mid-afternoon, and the ...


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[494] Attic duplex in the Alameda
Maksimum Konuk Sayısı4
Yatak odası1
Boyut75 metrekare
Floor No.2(with elevator)
- Aile / Çocuk dostu
- Mutfak
- Klima
- Çamaşır makinesi / Kurutma makinesi
- Etkinlikler için uygun
- Binada asansör
- Balkon/teras
Accommodation summary
|Alameda de Hércules, 41002 Sevilla, İspanya
|Mülkiyet türü
|Referans kodu
|Acceptance rate
|Response time
|A few hours
|Calendar updated
|3 weeks ago
The apartment is very bright and it has a terrace for private use with a view of the boulevard of Alameda de Hércules.
It is the ideal accommodation for two couples or a family of four people The apartment has a library with a double sofa bed, bedroom with a double bed, living and dining room, kitchen and a bathroom with shower.
The apartment is perfectly equipped to make your stay very enjoyable. It has air conditioning with heating, hot water, satellite TV, and Internet Wifi 24h.
The kitchen has a big fridge/freezer, washing machine, vitroceramics, oven, microwave with grill, and small electrical appliances such as coffee-maker, kettle, toaster, juicer and mixer. There is also kitchenware for four people staying in the apartment: dishes, cutlery, glassware, saucepans and other kitchen utensils.
Linen for the household is provided: table linen, bed sheets, bedspread, blankets and towels.
There is also a hairdryer and electric iron.
In the apartment you will find soap, toilet paper, bin bags, dishwasher detergent as well as laundry detergent for the first day of your stay.
We wish you a very pleasant stay.
Ev kurallarıCheck-in from 15:00 to 21:30.
From 21:30 to 23:30, there is an extra charge of 25€.
From 23:30 to 01:00, there is an extra charge of 40€.
From 01:00 on, the charge is of 60€.
These amounts must be paid on cash at the check in.
Check-out before 12:00.
Security deposit €150
|Weekly rate for up to 4 guests
|> 4 misafir için ücret
|TRY 42 misafir başına/ekstra gece
|Check-in Saati (Sonrası)
|Check-in before
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Nicely located appartment with beautifull terace on the roof. Kitchen is minimum but enough to make your coffee in the morning.
We were happy to stay in this appartment, and the owner (Eva) is very hospitable. The appartment has a very charming terrace, where we spent most time. We liked the area, where the appartment is situated with its many local bars, and would like to recommend a stay in this appartment.
The appartment is located in a great area of beautiful Sevilla, you can walk easily to nearby Pubs, Restaurants, Shopping places!
The appartment has got evrything u need, a huge comfy bed with room for 3persons!! the room is small,but nice!
Great terace upstairs!
We enjoyed our stay really much, thanks a lot, we will come back for sure!!
Very nice appartment, very functional and furnished with everything one might need. Moreover it's perfectly located Close to Train Station and City Center. For a longer stay it might be a bit dark, as it has only Windows to a courtyard,
The apartment was just great. Clean and easily walkable to all interesting areas of Seville. The only reason I did not give it 5 stars was that the noise from the street filters into the apartment, the windows could do with thicker glass. Carmen was always ready to answer any questions we had, and everything worked out just fine. I would recommend.
Luxurious and spacious appartment at a great location in Sevilla! We stayed with 8 persons one week, and it proved to be enough room for all of us. When on vacation location is important, and with the Parque Marie Louisa just across the street, location was well cared for. And it took only 10 to 15 minutes to walk through the park to the city center.
We were also very happy with the service, both in renting the appartment and in service on the spot. It was easy to arrange for us to be picked up from the airport (and brought back) for a very reasonable fee.
Advise: make a plan on who will shower when, because the warm water capacity per run was limited.
All in all we can recommend both this appartment and our host Carmen!
Nice and cosy apartment with a marvellous roof terrace. Positive: everything is available to make a decent meal, the apartment is clean, it has a "double bed" (not a twin bed) and a nice view from the terrace. Only point that could be improved: the amount of hot water due to the capacity of the boiler.
This is a really new apartment. Although it's not in the down town but very near to the metro station. With the taxi from down town to the apartment you just need to pay about 10 Euro.
What not good we feel is: there is NO WIFI or INTERNET! It's really extremely inconvenient! Especially for the tourists, who want search for the route or sth. else.
Perfect located. It´s a small studio but the large terrace makes all the difference. Very well equipped kitchen, and nice large bathroom.
This was a really fantastic apartement with a nice kitchen and modern bathroom. Special was the roof-garden with a great view on the city. We would book this place anytime again. We have there a pleasant stay.
- Kalite güvenceli konaklama
- Her ev sahibi telefonla doğrulanmıştır
- SSL şifrelemesi ile güvenli ödeme


text: Hard Boiled Sweets (2012) 720p BluRay x264-PFa Language(s): English | Subs: English 1hr 24mn | 720p BluRay | mkv | 1280 x 544 | x264 @ 4030 Kbps | DTS @ 1510 Kbps | 3.29 GB Genre(s): Thriller iMDB iNFO Ex-con Johnny (Scot Williams, The Crew) is forced into pulling a heist he wants nothing to do with. Mob Boss 'Shrewd' Eddie (Paul Freeman, Raiders of the Lost Ark, Hot Fuzz) has one million in dirty cash stashed at his home, just waiting to be stolen. But what Johnny doesn't know is that seven other dangerous criminals also have plans to steal the money. (Buy premium account for NETLOAD maximum speed and resumming ability) Download From Netload Code: http://www.netload.in/dateiOOPS6ZIVdB/pfa-hbs.720p.part3.rar.htm http://www.netload.in/dateiW1j4oY0zf6/pfa-hbs.720p.part1.rar.htm http://www.netload.in/dateiWMXTfXIsT0/pfa-hbs.720p.part2.rar.htm


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Hotel Hauser is located at Schellingstrasse 11 in Munich. Hotel Hauser is centrally located in one of the most versatile district of Munich. Schwabing, where art, culture, science and the hustle and bustle of life are united, is the right place for an interesting and eventful stay. Hotel Hauser, 65...
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Scalp Micropigmentation to camouflage 4000 FUE scars? advice? Cost?
Doctor Answers 2
The cost of Scalp MicroPigmentation like any cosmetic surgery is variable. It also depends on the work involved.
The cost of Scalp MicroPigmentation like any cosmetic surgery is variable. It also depends on the work involved. There is no down time but you would likely need more than one session. SMP is considered permanent like a tattoo is considered permanent.
Web reference: https://newhair.com/resources/
Scalp micropigmentation
If you just want to treat the donor area (back and sides of the head) the cost is $3,500 and it takes three sessions, one week apart. It is permanent. Results are instantaneous and there is no down time. Direct sun exposure is never good for any form of tattoo. It will last your lifetime.
Web reference: https://scalpmicropigmentation.com/
These answers are for educational purposes and should not be relied upon as a substitute for medical advice you may receive from your physician. If you have a medical emergency, please call 911. These answers do not constitute or initiate a patient/doctor relationship.


text:
Skye: Once bitten, twice as deadly
"Leave and tell Daemon this. He got a problem then he deal with it personally himself" Winter hisses. "Cause if he tries this again, he will be the one dead," says Winter. I start to run, then use Air to lift myself up and sort of half air run half fly. I get about a mile before I stop, due to the pain in my head.
You idiot. Get back there.
I can't kill her.
Yes you can. You've killed her once, she isn't dead. So go and kill her again.
This sounds sensible to me. I guess I'm insane right now but I like it.
I use Air to get myself back in a second and stay hidden. I watch them carry her to the door. I smile, life has taken a huge turn since she looked at me like that. Once bitten, twice as deadly certainly fits here. I press my palm to the wall, sending electricity along it and barring the door with an electrical barrier. Winter looks at it, confused, then see's me.
"I thought I told you to go," she hisses.
"Yes, you did. And in doing so you've turned me into an insane asassin. Instead of not wanting to do this, now I really do," I say, smiling. I through the target ball faster thsan the eye can track. She jumps out of the way, which is what I knew she would do. It flies past her and hits Ivy. With about ten storms power now. She falls to the ground. Winter looks at me, burning with anger, hatred and loss, but then she just collapses into a heap, crying.
"I'll kill you," she says, but her hearts not in it.
"So likely. As if you could catch me. Besides, I'm used to it," I say, dropping Ivy from about three miles up. I then float up my self, dodging several bolts of electricity and fighting back with lightning.
"Murderer! I'll never give up," she yells at me, her eyes still full of tears.
"No rest for the wicked," I shrug, then float back to the Dementa. It's like that stupid cathedral, or creational, or whatever, but obviously it's the Daemons.
"So," he says, when I get back. " You are truly on my side now?"
"Yes," I say, without hesitation.
"Good. You are one of the most powerful in the Kingdom or Freedom already, but as a Freedomer you do have more power. My personal asassin."
Some bit of me that would have hated that once shivers, but I stamp on it till it goes out like a spark.


text:
Henderson to coach on TUF
Dan Henderson will serve as coach of the American team for season nine of "The Ultimate Fighter: US vs. UK" premiering Wednesday, April 1 at 10:00pm ET/PT on Spike TV. Henderson earned the right to coach after defeating former middleweight champ Rich Franklin via split decision after an intense bout at UFC 93 last Saturday night. He will be opposed by British sensation Michael Bisping. Production for "The Ultimate Fighter: Team US vs. Team UK" begins this Friday, January 23 in Las Vegas . . . Click here for more


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If you want to view the logs from another site, you must log on to a server at the remote site from the Symantec Endpoint Protection Manager console. If you have an account on a server at the remote site, you can log on remotely and view that site's logs.
If you have configured replication partners, you can choose to have all the logs from the replication partners copied to the local partner and vice versa. If you choose to replicate logs, by default you see the information from both your site and the replicated sites when you view any log. If you want to see a single site, you must filter the data to limit it to the location you want to view. If you choose to replicate logs, be sure that you have sufficient disk space for the additional logs on all the replication partners.
See How to install a second site and configure it for replication.
To view the logs from another site
Open a web browser.
Type the server name or IP address and the port number, 9090, in the address text box as follows:
The console then downloads. The computer from which you log on must have the Java 2 Runtime Environment (JRE) installed. If it does not, you are prompted to download and install it. Follow the prompts to install the JRE.
In the console logon dialog box, type your user name and password.
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Battery question for a Meyers sander
Discussion in 'Ice Management' started by Jason1919, Oct 12, 2013.


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Ardell LashLites style 331 are premium false eyelashes - they're subtle, delicate and extremely lightweight - they're comfortable to wear too.
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Gabriela Mistral University
From Wikipedia, the free encyclopedia
(Redirected from Universidad Gabriela Mistral)
Gabriela Mistral University (Spanish: Universidad Gabriela Mistral) is a privately funded university in Santiago, Chile.
External links[edit]
Coordinates: 33°25′55″S 70°36′22″W / 33.432°S 70.606°W
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text:
I'm interested to know this as well my father is looking at buying one.
This is a discussion on Kimber Raptor II opinion please within the Defensive Carry Guns forums, part of the Defensive Carry Discussions category; Hi Fellow Shooters, I have been thinking about adding a 1911 to my small collection. One of my LGSs has a Kimber Raptor II that ...
Hi Fellow Shooters,
I have been thinking about adding a 1911 to my small collection. One of my LGSs has a Kimber Raptor II that I may be able to get a good deal on. I had previously thought about a Springfield Armory 1911 Loaded as my entry into this world but the Raptor looks pretty cool (albeit more expensive). For those of you who have had Kimber 1911s, what is your opinion? Pass on the deal and look for a less expensive one? Go for it? Thanks.
NRA, IDPA, GSSF & GSSA member
Certified Glock Armorer
I'm interested to know this as well my father is looking at buying one.
I would opt for the Spinger. Very nice 1911. I've personally seen too many Kimbers malfunction to ever own one. JMO
Sportsterguy-NRA Life Member
Molon Labe!
Join the NRA today, or don't complain when your guns are taken away!
I've seen FTE and FTF's multiple times with 5 different "broken in " full size Kimbers while shooting our monthly IPSC matches. One gent sent his back to Kimber 5 times and still had problems. He ended up seing it cheap and was disgusted with Kimbers customer service. Yes magazines were changed out and ran to see if they were the problem. All of these were with ball ammo, so I think the problems would increase with JHP's. They are beautiful weapons, but I'll take reliability over nice lines any day of the week. JMO and observations.
Sportsterguy-NRA Life Member
Molon Labe!
Join the NRA today, or don't complain when your guns are taken away!
I have 2 kimbers, a tack pro and a stainless steel . Have about 4,000 roumds through each no priblems. The main thing with a kimber is keep them clean and lubed.IMO a very dependable gun. Will buy another if the price is right.Have had mine about 4 years now.
I bow to one king, and serve only one kingdom
I to have had a kimber for over 4 yrs now-not 1 problem- like it was said keep it cleaned and lubed like any gun and it will work. The problems I have had were all mag problems(1 mag). IMO go for it!
I have a Kimber Custom II and love it.
Psalms 144:1
Blessed be the Lord my strength, which teacheth my hands to war, and my fingers to fight.
Senior Instructor for Tactical and Defensive of Texas
Retired LEO
NRA member
TCHA member
Between the Raptor and the Springfield there is no comparison. Jump on the deal. Take the Raptor.
As far as 'malfunctions' with a Kimber, well, there are malfunctions with any 1911 that is not tuned properly or maintained.
There are a lot more happy Kimber owners than unhappy. It just turns out the unhappy guys are louder than the happy ones.
The myth that Kimbers are somehow destined to be jam-o-matics is propagated over the internet and for the most part, by people who have never owned them. The friend of a friend who had a cousin who had a problem has became famous.
There are two sides to every issue: one side is right and the other is wrong, but the middle is always evil.
Who is John Galt?
I've got a Desert Warrior, it's been really good. Kimber has taken a lot of popularity hits on various websites lately, and at least some of that was earned. Their MIM parts had some QC problems and failures. And their external extractor proved problematic.
They've been replacing external extractor slides with internal from what I've heard. And hopefully they've gotten a grip on the MIM process (not inherently bad when done right).
If the gun is a good deal, and has an internal extractor, I'd consider it. They're a nice looking gun.
Regards, T Bone.
"Those who would give up essential liberty to purchase a little temporary safety deserve neither liberty nor safety". Benjamin Franklin
Every single Kimber I have owned has given me problems and the Kimber factory people are not what I would call co-operative.
Buy the Springer or a Colt. Or better yet, save your bucks for a really nice custom from Baer or Wilson. Another good choice would be a Nighthawk.
I have a Kimber Gold Match S.S and a Pro Carry....they have both been great guns to shoot with no problems. YES you do need to make certain they are cleaned and maintained.
Good luck on your decision
Kimber Pro CDP II
Kimber Gold Match Stainless Steel
Sig P-239 two-tone
I have a Kimber Custom II and Tactical Ultra II both have not given me any problems with ball or hollow point ammo. I also have a Springfield Stainless Loaded and it has been great also. The only thing I do not like about the loaded is the FLGR but that can be replaced. When I buy another 1911 it will be a Kimber.
Kimber Tactical Ultra II
Kimber Custom II
Glock 23, Sig Sauer P225, Kel-Tec PF-9
Attack him where he is unprepared, appear where you are not expected. SUN TZU THE ART OF WAR
I've got a Pro Carry which had big problems (failure to feed and extract) early on. I called the factory and they told me to change the recoil spring and break it in for 500 rounds. I did that and the problem still existed.
I called again and they had me send it to them. They couldn't have been nicer. The polished the ramp, changed the extractor and had it back to me in a week with three new mags and a handful of recoil springs. I haven't had a problem since.
Jeez, what a mix of opinions. Sounds like many folks who own Kimbers have no problems, other do. I appreciate all the input, guys. The "deal" is 22% off retail which I am suspecting is typical discount for this gun. I need to keep thinking about this. Might change my mind when I go see the gun again...
NRA, IDPA, GSSF & GSSA member
Certified Glock Armorer


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ED Magedson – Founder
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Labyrinth classic 2
By CureGame
Open iTunes to buy and download apps.
THE BEST GAME on the app Store! Remember playing with the classic wooden labyrinth? Now get a Labyrinth Classic 2 for your iPhone, iPod. Guaranteed 100% Addictive!
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iPhone Screenshots
Customer Reviews
I have to say that I enjoyed playing BUT two things I didn't like: it doesn't record my time or my best performance (for different labyrinth not in general) and I would like to have the option of hide the marked path, in order to make it more challenging.
Doesn't work well when it doesn't crash.
Not realistic at all
Lacks of smoothness and realistic ball movements. Feels like scripted and gif-animated.
- Free
- Category: Games
- Updated: Mar 04, 2011
- Version: 1.2
- Size: 7.4 MB
- Language: English
- Seller: Arnaud Cure
- © Arnaud Cure
Compatibility: Requires iOS 3.0 or later. Compatible with iPhone, iPad, and iPod touch.


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The scale of the challenge to public services was laid bare last week. After a decade in which we have done more with more, we will spend the next decade trying to do more with less – in some services, a lot less. The conventional public service response would be to restrict eligibility to services. The best we might hope for are Ryanair-style public services, cut back to a basic, low-cost offering; those who want to get a better service will have to pay more.
Both will lead public services into 10 years of tension and conflict, marked by rising resentment and declining trust among citizens, who will feel hard done by. To avoid heading down that cul de sac, we have to devise ways for people to find solutions to their needs that cost radically less and are more effective. Here is a seven-step guide to finding those approaches:
1 Prevent demand for public services arising in the first place. The dramatic decline in the number of deaths in domestic fires is not primarily due to better fire engines, but to the spread of the low-cost smoke alarm.
2 If a need arises, find ways to meet it without relying on public services. In Western Australia, the last of 16 options families with adults with learning disabilities are given is to see a state social worker. As a result, there are only seven social workers dealing with this group.
3 Help people self-manage a long-term need, rather than relying on a service. Many Germans who have a heart condition test their own blood and contact a doctor only if they get an unusual reading. The long-term costs are lower than relying on GPs and nurses to test blood.
4 Help people recuperate as fast as possible, thus limiting long-term service dependency. Six-week recuperative programmes for older people leaving hospital, helping them to avoid long-term dependency or life in a care home, have a huge pay-off. And prisons should be redesigned to reduce long-term recidivism and promote rehabilitation through learning.
5 Minimise duplication by integrating services around people and places. The London borough of Barnet recently found that a single workless household on one of its poorest estates was receiving 31 different services, to almost no effect. A more personalised, integrated approach is likely to save money, compared with the scattergun effect of disconnected services.
6 Allow service users to commission services directly. Personal budgets have huge potential to mobilise service users' intelligence to find lower-cost ways to improve services, while also allowing professionals to play a more creative role, rather than rationing the allocation of services.
7 Get it right first time and allow users to track progress. Public services would have more money for the frontline if they could answer queries first time round and allowed people to track the progress of the inquiry online, just as you can with a package from DHL.
In short, there are myriad ways for public services to help people more effectively, at lower cost. The alternative – a pared-back, rationed, often low-quality and low-cost version of an existing service – will just leave more people feeling resentful and, in the long run, unwilling to fund collective provision. Anyone who wants to avoid that outcome should start innovating.
• Charles Leadbeater is founder of public service innovation group Participle. More on his seven-step guide at Participle.net


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LONDON (AFP) – Manchester United will attempt to stave off an assault on their third-place position in the Premier League table when they welcome closest pursuers Southampton to Old Trafford on Sunday.
United have gone 10 games without defeat since losing 1-0 at joint-leaders Manchester City on November 2, but they have taken only six points from a possible 12 after drawing three of their last four matches.
It has prevented Louis van Gaal's side from fully exploiting recent slip-ups by co-leaders Chelsea, who they trail by nine points, and has allowed Southampton to close to within one point.
After a run of four straight defeats in late November and early December, including a 2-1 loss in the reverse fixture, Ronald Koeman's side have won three and drawn one of their last four games.
United were fortunate to claim victory at St Mary's last month, with Robin van Persie's brace representing two of the three shots on goal they managed to muster in the 90 minutes.
But United are in much finer fettle than they were a month ago.
Their injury glut has cleared to the extent that Ashley Young (hamstring) is the only player currently unavailable, while the squad was bolstered on Thursday with the eye-catching acquisition of former Barcelona goalkeeper Victor Valdes.
It leaves Van Gaal with an enviable selection dilemma on his hands.
Over the festive period, the Dutchman devised a system that accommodated Wayne Rooney, Juan Mata, Van Persie and Radamel Falcao, and he must now find a way of fitting Angel di Maria into his team as well.
The Argentine winger made a goal-scoring return from a pelvic injury in United's 2-0 win at third-tier Yeovil Town in the FA Cup third round last weekend and could start against Southampton.
"Angel di Maria has played only 20 minutes and that's because of the match rhythm that I gave," said Van Gaal.
"I have said I have only one injured player (Young), but I don't have 100 percent match-fit players. That's a different thing.
"But of course Di Maria is for example further than Daley Blind or (Marcos) Rojo.
"I have to select the best team and also I have to watch the qualities of Southampton, how I can reduce that quality by my line-up, but also by our game-plan."


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Skana Spa at Turning Stone - 0 miles
Turning Stone Resort Casino - 0.5 Miles
Kaluhyat Golf Course - 2 Miles
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Vernon Downs Race Track - 6 Miles
Boxing Hall of Fame - 8Miles
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International Boxing Hall of Fame Canastota - 12 Miles
Sylvan Beach and Lake - 12 Miles
Oneida Lake Fishing Dining - 13 Miles
Sylvan Beach and Amusement Park - 13 Miles
Colgate University - 15 Miles
Hamilton College - 15 Miles
Matt Brewing Company - 25 Miles
Utica home of the Boiler Maker Road Race - 25 Miles
Syracuse - 30 Miles
Syracuse University - 35 Miles
Adirondack Mountains - 50 Miles


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Train - Travel
Train & Travel Israel December 2016
The program will be conducted by IKMF chairman Avi Moyal along with the Israeli GITs Participants should arrive to the Caesarea Sea Center on December 26th. Actual training shall commence the next morning at 09:00hrs. Opening meeting at location's lobby. Training ends at 15:00 hrs on January 3rd 2017. accommodations are on b&b basis. early bird discount until October 1st.
arrivle 26/12 starting 27/12 For further info please contact IKMF HQ at: email@example.com
Start: 12/26/2016
End: 01/03/2017
Registration fee: 100 EUR
Total costs: 1690 EUR
Registration form
After submitting the registration form, you will be redirected to Paypal to pay the registration fee
Please note that the total amount is only for the specified seminar and or the specific part of the course


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The Lodi Legion baseball team defeated West Sacramento 8-2 in the first round of the District Tournament on Wednesday night in Woodland.
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Cicero-North Syracuse (Northstars)Route 31, Northstar DriveCicero, NY 13039315 • 218• 4100
Athletic Director: Tim Bednarski firstname.lastname@example.com Deptartment Secretary: Cassy Wheaton email@example.com Department: 315-218-4114Fax: 315-218-4186Website: www.cnsathletics.com
A public school's athletic program is a valuable tool. It can motivate, inspire, teach, and empower students to aspire beyond artificial limitations. Athletics can provide opportunities for achievement beyond scores and times and medals.
Interscholastic athletics can bring out the best in individuals, and teach about the value of teamwork and hard work. North Syracuse Schools is very proud to provide our student athletes with the best chances to learn, to excel, and to achieve. This website has been developed to communicate the various happens of the department and provide information for the best possible experience for our students.