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21 September 2016
The report finds that any changes to migration policy post-Brexit could have serious implications for the adult social care workforce....
Tagged categories include: Care, Health, International
04 August 2016
Pension reforms in the UK are transforming the way that citizens, especially those who lack access to an employer funded pension scheme,...
Tagged categories include: International, Pensions
17 September 2015
This is one of the messages of a major new report 'Creating a sustainable 21st century healthcare system' by the...
Tagged categories include: Economics of Age, Global Ageing, Health, International, SOS 2020 Health
04 February 2015
We have considered how European policymakers are responding to the need to better support older workers in Working longer, an EU...
Tagged categories include: International, Work and Retirement
20 November 2014
This report estimates that the Eurozone's economy could lose one in six workers due to population ageing. It also shows that...
Tagged categories include: Economics of Age, International, Work and Retirement
05 November 2014
While it is currently the Northern and Western European countries which have the oldest populations, by 2060 many of the countries in...
Tagged categories include: Care, Health, International, Pensions, Work and Retirement
02 May 2014
The report highlights the demographic changes facing Scotland over the next 20 years - revealing that:
- By 2037, Scotland's...
Tagged categories include: Economics of Age, International, Quality of Life
27 March 2014
A working paper by David Hayes of the Personal Finance Research Centre under the financial wellbeing in older age programme of work...
Tagged categories include: Economics of Age, International, Quality of Life
19 November 2013
SAATI is a voluntary, pan-European partnership of individuals, from a variety of backgrounds including clinicians, health promotion...
Tagged categories include: Health, International, Quality of Life
13 November 2013
In light of these challenges, the SAATI Partnership has launched their report on "Adult vaccination: a key component of healthy...
Tagged categories include: Health, International
08 March 2013
While it is widely acknowledged that the world is ageing, the intersection of age with gender has been historically ignored. As men and...
Tagged categories include: Care, Equality and Human Rights, Global Ageing, Health, International, Pensions, Quality of Life, Work and Retirement
10 December 2012
"The cost of our ageing society", sponsored by Milliman, highlights the projected financial impact of the cost of the world&...
Tagged categories include: Economics of Age, Future of Age, International, Transport
01 August 2012
The report features a description of the global challenge of ageing and highlights a number of innovations that could help to reduce the...
Tagged categories include: Care, Future of Age, Global Ageing, International
12 August 2011
This report examines the relationship between population ageing and urbanisation, based on the contrasting experiences of Japan and the...
Tagged categories include: Communities and Housing, International, Quality of Life
04 April 2011
The International Longevity Centre Global Alliance dinner debate on 'Narrowing World Health Disparities and Longevity' was...
Tagged categories include: Health, International, Longevity
24 February 2011
The report, 'The European Dementia Research Agenda' finds there is widespread disparity in the diagnosis, treatment and care...
Tagged categories include: Dementia, Health, International
03 February 2010
With 7.3 million Europeans living with dementia and with the numbers set to increase to 15 million by 2050, this policy brief argues all...
Tagged categories include: Dementia, International
16 October 2007
You can download a copy of this report here.
We are very grateful to BT whose generous support has made this unique report possible..
Tagged categories include: Equality and Human Rights, International
28 June 2006
The International Longevity Centre-UK and The Merck Company Foundation have collaborated to publish The State of Ageing and Health in...
Tagged categories include: Global Ageing, Health, International


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December 19, 2016
Category: InspiringApps News
Happy Holidays!
As 2016 draws to a close, we want to take a moment to express our gratitude to you – our clients, partners, and friends – for another wonderful year.
We hope you have a joyful holiday season!
November 21, 2016
Category: Events
NewCo Boulder 2016 Inspires Us
Boulder had the privilege of hosting its third NewCo festival last Friday, and we were thrilled to be able to participate. With a mission to "identify, celebrate, and connect the engines of positive change in our society," NewCo provides an opportunity for purpose-driven businesses to share their stories with entrepreneurs, job applicants, and potential customers that want to learn from them. Thanks to the efforts of Engage Colorado, around fifty innovative Boulder companies opened their doors and invited participants to come see for themselves how passion and purpose change "work" from simply a job to an endeavor that can change the world. Read More
December 21, 2015
Category: InspiringApps News
Holiday Greetings 2015
Wishing you a festive holiday filled with joy and inspiration!
Our designer, Stephanie, snapped the beautiful photo above. We invite you to download the image as a background for your device.
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November 23, 2015
Category: Events
NewCo Boulder 2015: 8 Lessons Learned
NewCo took Boulder by storm last week and the team at InspiringApps enjoyed participating in the varied presentations around town. We were encouraged at QuickLeft to be intentional about diversity, and glad to see others such as Pivotal Labs committed to lean methodologies. We also enjoyed a tour at eTown, got recruiting tips from Turning the Corner, and one of us even tried brussels sprouts for the first time at the Made in Nature session!
Not only did we learn about our neighbors and the cool and innovative things they're working on, but we also hosted a session in our office. Our CEO, Brad Weber, presented "8 Lessons Learned in 8 Years of Making Mobile Apps." As Brad shared a few pivotal stories from our history, he drew out key concepts and provided some salient wisdom for any entrepreneur or business leader:
Don't partner when you can hire. Although starting alone can feel daunting, hiring may be a better way to begin. A partnership is a serious and long-term relationship and, as the team at TechStars also noted, it's important to know as much about a potential co-founder as one does about a potential life partner.
Hire with an eye toward the future – but not the distant future. Resources are limited in the early days, so it's important to be thoughtful about what skills can take the company to the next horizon.
Building a team of employees is hard work, but worth it. Using contractors seems to offer the promise of less risk, but it has its own set of challenges. Investing in an all-employee team can lead to better cohesion, mutual commitment, and lots of fun!
There is value in working under one (leaky) roof. Flexible out-of-office hours are a key part of our culture, but we gain a lot by also having one space in which to collaborate together.
Without project management, there is chaos. It's tempting to forego the overhead of project management, but a client-based business benefits greatly from such leadership.
Lean is a better approach to development. A desire to get things just right causes many companies to invest too much and wait too long to release a product. Using small, iterative steps enables a company to be more nimble – and gain better market feedback along the way
Align costs and revenues to bid projects. Instead of fixed bids, we often found it better to use high-level estimates for the whole project, then time and materials for a given sprint.
It's a delicate balance between product work and custom development work. Client work pays the bills, but it can't drive all the priorities in resource allocation. Maintaining steady progress toward other goals (in our case, product development) is required to keep the momentum going.
If you'd like to learn more details about what Brad shared, contact us and we'd be happy to share.
November 13, 2015
Category: App Development
InspiringApps Wins a Prestigious Tabby Award
We're excited to share that the retail merchandising app we created for SmartWool was named the 2015 winner of the Tabby Award /Business in the iPad App: Data Access & Collection category! We are thrilled to join ranks with other companies who have been in the winners circle like Citrix, SAP, Morningstar, RosettaStone, and Adobe.
The Tabby Award /Business is the only global competition that recognizes the top enterprise and business apps in the industry. Apps are evaluated on numerous criteria, including overall business value, user experience, design, innovation, tablet optimization, and performance. As a company that strives to demonstrate best practices in leveraging technology, we are honored that other industry leaders recognize our commitment to excellence.
An international panel of 24 judges reviewed over 150 apps before selecting the winners. With more than 300,000 business apps collectively available on Android and iOS devices, winners are positioned in the top 0.01% of all apps. "The lineup of apps this year was incredibly impressive," noted judging panel chair Carson Conant, CEO of Mediafly. "The slate of apps this year brought the perfect mix of business utility and the clean interfaces that you see in the best consumer apps."
The SmartWool app leverages the extensive experience we have in helping organizations of all sizes to collect, access, and successfully employ business-critical data. This expertise was recognized by the judging panel, who stated, "We immediately recognized the value of the SmartWool FSR app for streamlining field data collection, decreasing reporting time, and improving store service. We found the app to be highly intuitive with clear dashboards and reporting."
As you may recall, a sales presentation app that we developed in conjunction with Gulfstream Aerospace was also one of two finalists for a different Tabby Award. In this case, we must tip our hat to Adobe for winning the iPad App: Marketing & Presentation category. Congratulations!
September 10, 2015
Category: App Development
The Tabby Awards: Honoring the Best in App Development
We are so excited and humbled to have our work commended by The Tabby Awards! The Tabby Awards /Business is the only worldwide competition designed to honor the best mobile apps for businesses and professionals.
Over 150 apps were evaluated this year and just 40 iPad-optimized apps were selected as nominees for the final round. Submissions are judged on a number of factors, including user experience, innovation, design, performance and reliability, and the business value that they add to an organization. Only those that excel in multiple categories move forward. Nominees and winners are selected by an international panel of independent app experts.
An app we developed for Gulfstream Aerospace was nominated in the Marketing and Presentation category. Gulfstream is renown for creating and delivering the world's finest aviation experience, and they wanted this client touchpoint to reflect their commitment to excellence. Built as a sophisticated mobile education tool, the app showcases the aesthetics of the jet's interior and exterior, explains Gulfstream's technological advances, shares critical performance characteristics, and introduces the company's award-winning customer support.
Another app, developed for leading outdoor brand SmartWool, is a contender in the Data Access & Collection category. The app is used by SmartWool's field sales reps to improve their effectiveness at retail merchandising. Merchandising plays a critical role in the sell-through of products, but is time-consuming and error prone. Reps are able to use the app to quickly capture and share information about point-of-sale (POS) signage, displays, and stock levels. In addition to cutting reporting time in half, the app helps them to service accounts more quickly.
While different in their function, both apps are valuable sales enablement tools that are making a difference to those who use them.
Learn more about these projects and others by visiting our Clients page.
January 29, 2015
Category: InspiringApps News, IA Team
Team Member Profile: Ralph Dosser, Software Engineer
Ralph was born and raised in northeastern Tennessee in a town called Johnson City as the fifth of six kids. He spent his childhood enjoying comic books and running his paper route. His love of the outdoors started early, when he frequently hiked the Appalachians with his scout master dad. When Ralph was 17, he embarked on his first trip west with the Boy Scouts to Philmont Scout Ranch in New Mexico. After seeing the vistas for the first time, he instantly fell in love and knew he would eventually head west permanently. After 15 years, the dream became reality.
But first Ralph studied journalism, then spent the next several years working for small newspapers in East Tennessee. He left journalism to study computer science at the University of Tennessee in Knoxville after his sister – who worked in the computer science department there – showed her boss Ralph's GRE scores and got him a graduate assistantship. Ralph worked at the university for awhile, eventually moving to research administration. When writing technical documentation for the department of network engineering, his boss asked him to make it available via the internet. How? A new thing called "the world wide web." Within months, Ralph was making websites for the school using this new revolutionary technology.
Using his expertise in building websites, Ralph moved to Atlanta to work for CNN, helping to get cnn.com up and running in 1995. He states that it was really exciting work because "we were making everything up as we went along." The first really big story on the site was the OJ Simpson verdict in 1995, followed by the Clinton/Gore presidential election in 1996 which killed the servers because of the load. "We couldn't throw hardware at it fast enough," Ralph recalled. During his time at CNN, Ralph helped to build the CNN/Sports Illustrated site, the financial site, and the politics site for the brand. He moved on to work for Cox Interactive Media and then as a contractor for IBM interactive where he helped to build sites for the Grammys, the NHL, the NFL, and the Hermitage museum.
Around that time, Ralph planned a vacation to Boulder, CO and then spent the next year looking for a job here. He found one with XOR Network Engineering and moved west in 2000, making that childhood dream come true. The company started to unravel during the first internet bust and Ralph switched to contracting for a few years. He contracted with InspiringApps and soon became employee number three (after Brad and Aaron Gerber)!
Ralph enjoys working for InspiringApps because "the work varies a great deal." Ralph states that since InspiringApps is small, there is not a lot of hyper-specialization, allowing him to write code, talk to a client, work on a server, and investigate a database…all in the same week. "Our small size keeps us nimble and we have a good culture and environment. The location and view are wonderful and I'm still very much in love with Boulder," says Ralph. "The scenery, the mountainous beauty that is right there. The bike culture is great. I like the outdoorsy culture."
In his spare time, Ralph likes to tinker with hobby electronics ("pretty blink-y lights"), do a little soldering, and program Arduinos. He's built some cool stuff for his trips to Burning Man and gets a lot of inspiration from that event and the amazing engineering and art on display there. Ralph tries to bring that inspiration back and integrate it into his work and non-work life.
January 7, 2015
Category: InspiringApps News
The Developer's Paper Kit
Enjoy a little new year's fun we cooked up in the InspiringApps design lab – The Developer's Paper Kit! Ready your printer, sharpen your scissors and locate that glue (it's in your junk drawer, remember?) Choose a character and get your craft on!
Send a photo of your creation to email@example.com and we'll post it for everyone to enjoy.
December 2, 2014
Category: InspiringApps News, IA Team
Team Member Profile: Michele Connors, Marketing Director
Michele recently joined InspiringApps as our Marketing Director. She comes with a wealth of experience in marketing, especially for the active and outdoor markets, due to her 15 plus years working for the GORE-TEX brand.
Michele grew up outside of Pittsburgh, Pennsylvania where she spent her days running around the neighborhood, meeting friends at the pool, and playing kickball in the streets. Some of her favorite childhood memories stem from camping in the gorgeous hills of central Pennsylvania.
Although she attended a high school with a strong STEM emphasis, an interest in broadcast cable led Michele to begin her college years as a Communications student at Penn State University. She soon realized, though, that she missed being more technically focused. She switched gears to engineering, and graduated with high honors in Mechanical Engineering in 1993, confident she'd still be able to use her communication skills along the way.
After college, Michele accepted a position at W.L. Gore & Associates, a company known for its unique corporate structure and innovative products. She worked in product and technology development for a number of years, then moved to product management, and finally landed in the marketing world. Michele jokes that joining the marketing group was likened to "going to the dark side" since she was no longer involved with product technology or development. But the dark side was kind to Michele. In a recent 3-year period, she achieved strong GORE-TEX® brand presence online and doubled the number of sites telling their brand story.
Michele has always loved the business side of things. She enjoys watching the lights go on as potential customers realize why a product is worth their money. At InspiringApps, she is excited for the opportunity to spread the word about what we do well, helping us to grow into new market areas. We are thankful for her dark-side experience!
Outside of work, Michele loves to help create community, often over a shared meal or a glass of wine! She is grateful to live near world-class mountains, and getting to hike, camp and ski in them is a fabulous treat – especially if friends or family are involved too. Michele and her husband are raising four kids, so many weekends involve sporting events, Girl Scout activities, or other kid-centric fun. "It's a full life," Michele states, "but I am very grateful for it."
December 20, 2013
Category: InspiringApps News
Happy Holidays!
From our team to you, we'd like to wish you an inspiring holiday season. We're grateful for all of you and look forward to working with you in the New Year!
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subset: commoncrawl


text:
Axitinib in Metastatic Renal Cell Carcinoma
- 1.4k Downloads
- Citations
Targeted agents have revolutionized the management of metastatic renal cell carcinoma (RCC). Axitinib, an inhibitor of vascular endothelial growth factor receptor (VEGFR), has been an important addition to currently available therapies for advanced RCC. Its ability to inhibit VEGFRs at nanomolar concentrations distinguishes it as a potent tyrosine kinase inhibitor, with increased selectivity for VEGFR-1, 2, and 3 at clinically applicable concentrations. The phase 3 AXIS trial has established its superiority in prolonging progression-free survival (PFS) in previously treated RCC patients (median PFS 6.7 months for axitinib vs. 4.7 months for sorafenib). Common toxicities of axitinib include hypertension, diarrhea, nausea, hand-foot syndrome, fatigue, and hypothyroidism. Axitinib-induced diastolic blood pressure elevation may be associated with improved clinical outcome, likely reflecting the "on-target" effect of axitinib. Dose escalation to achieve therapeutic plasma drug levels is of considerable clinical interest. Although axitinib has established efficacy in patients treated with one previous agent, its use in the frontline setting is currently the subject of ongoing research.
KeywordsAdvanced renal cell carcinoma Axitinib Oncology Pharmacodynamics Progression-free survival Vascular endothelial growth factor receptor
The treatment of metastatic renal cell carcinoma (mRCC) has historically included immunotherapy, although targeted agents have revolutionized treatment strategies over the last several years. The management of mRCC has evolved rapidly since 2005, when sorafenib, a tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR), was approved for advanced RCC following a phase 3 study in patients who had failed to respond to prior systemic therapy [1, 2]. Since then, newer VEGFR inhibitors, including sunitinib and pazopanib, have been approved in advanced renal cell carcinoma (RCC) in 2006 and 2009, respectively [3, 4, 5]. Additionally, bevacizumab, a monoclonal antibody to circulating vascular endothelial growth factor (VEGF), was approved in 2009 for mRCC patients in combination with interferon alpha [6, 7]. Newer, more biochemically potent VEGF-TKIs, such as axitinib, have expanded the armamentarium of available drugs with targeted action and established efficacy in mRCC.
Angiogenesis and neovascularization are key to proliferation and dissemination of neoplastic cells in many solid tumors. In sporadic RCC, mutations in the Von Hippel-Lindau (VHL) gene lead to decreased degradation of hypoxia-inducing factor (HIF), and subsequent upregulation of VEGF expression [8]. VEGF, a mitogen of endothelial cells, promotes angiogenesis and vascular permeability. Additionally, it also induces expression of plasminogen activators and metalloproteinases; thereby, promoting a prodegradative environment, facilitating cellular migration and invasion [9]. Downstream signaling upon activation of VEGFRs has also been associated with inhibition of apoptosis and decreased production of nitric oxide [10]. Thus, the VHL-HIF pathway is pivotal to the pathobiology of RCC, and has been crucial in the development of targeted agents that include VEGFR inhibitors as well as antibodies to circulating VEGF. Furthermore, mammalian target of rapamycin (mTOR) molecules that are downstream of phosphoinositide 3-kinase and protein kinase B pathways have also demonstrated an increased concentration of HIF-alpha; thus, playing a significant role in angiogenesis [11]. This has expanded available molecular targets and led to the development of mTOR inhibitors, temsirolimus and everolimus, which have demonstrated efficacy in mRCC [12, 13].
Since its Food and Drug Administration (FDA) approval in January 2012, the receptor selectivity, potency, high objective response rate (ORR), and tolerability of axitinib have generated considerable interest. The clinical evidence supporting the current role of axitinib in the management of mRCC is reviewed in this article, with a special emphasis on its place in current treatment regimens. In addition, management of drug toxicities and ongoing investigational trials centered on axitinib are detailed.
A PubMed search was conducted using the key terms "axitinib" and "renal cell cancer." Additionally, proceedings from major congresses in North America and Europe over the last 5 years were reviewed for abstracts related to axitinib in RCC.
Mechanism of Action
Axitinib is a second-generation, indazolederived molecule that inhibits VEGFR-1, 2, and 3 at therapeutic plasma concentrations; thereby, blocking VEGF-mediated angiogenesis, cellular adhesion, migration, and eventually resulting in cellular apoptosis. Axitinib binds selectively to the adenosine triphosphate (ATP)-binding intracellular domain of VEGFR-1, 2, and 3 at nanomolar concentrations, stabilizing an inactive confirmation of these kinases and, thus, inhibiting downstream signal transduction [14, 15]. In fact, the half maximal inhibitory concentration (IC50) of axitinib for VEGFR-1, 2, and 3 inhibition is 0.1, 0.2, and 0.1–0.3 nM, respectively, distinguishing it as the most potent VEGFR-1 inhibitor for the treatment of mRCC [16]. Despite platelet-derived growth factor receptor and C-Kit inhibitory effects observed in vitro, axitinib's potency against non-VEGF receptors is about eight-times weaker and, at clinically achieved plasma levels, VEGF inhibition alone is believed to be responsible for the observed clinical benefits [10]. This selectivity is likely responsible for the potent "on-target" effect and toxicity profile of this agent.
Clinical Data
In the first phase 1 study of axitinib, 36 patients with advanced solid malignancies were treated with axitinib with total daily dose varying from 10–60 mg [17]. This trial helped define the maximal tolerated dose of axitinib as 5 mg orally twice a day (b.i.d.). Important dose-limiting toxicities included hypertension, diarrhea, and stomatitis. The incidence and severity of hypertension were proportional to drug dosage. Linear pharmacokinetics were observed in the dose range evaluated in this trial. Subsequent phase 1 studies conducted among Japanese and Chinese patients have confirmed similar pharmacokinetics and the adverse-effect profile of axitinib in non-Caucasian subjects [18, 19]. Another phase 1 study of axitinib in 12 Japanese patients confirmed the tolerability and efficacy of this dose, and demonstrated a significant correlation between axitinib exposure and decline in soluble VEGFR-2 levels [20].
Subsequently, a second phase 2 study of 62 patients was conducted to evaluate response to axitinib in patients who had received prior VEGF therapy with sorafenib [22]. In this single-arm study, dose escalation was permitted if standard 5 mg b.i.d. dosing was tolerated. Additionally, the protocol allowed for dose reduction or interruption for grade 3–4 (severe, disabling, or life-threatening) nonhematologic toxicities (per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE], version 3.0). A total of 53.2% of patients were able to tolerate dose increases to 7 or 10 mg b.i.d, while 17.7% of patients required dose reductions to ≤5 mg b.i.d. The primary endpoint of ORR was 22.6% (95% CI 12.9–35.0%). With a median follow-up of 22.7 months, median progression-free survival (PFS) was 7.4 months (95% CI 6.7–11.0 months), and median OS was 13.6 months (95% CI 8.4–18.8 months). Interestingly, 80% of the evaluable patients had some degree of tumor shrinkage.
A phase 2 study of axitinib in Japanese patients who were cytokine refractory has also yielded similar results, with an ORR of 50.0%, and median PFS of 11.0 months, which confirms the previously observed efficacy and tolerability in non-Caucasian populations [23].
Phase 3 AXIS Study
The prolonged PFS with both axitinib and sorafenib in sunitinib-refractory cases, although modest, provides evidence favoring lack of cross-resistance between different VEGFR inhibitors. These data support the use of sequential VEGFR inhibitors, although optimal sequencing to maximize PFS in mRCC is currently the subject of ongoing research [26, 27, 28, 29].
Secondary analysis of the AXIS trial has suggested that of the nearly 54% of patients (in both sorafenib and axitinib arms) who had received prior sunitinib, those who had received ≥9 months of front-line VEGFR inhibitor tended to have greater PFS (6.3 months vs. 4.5 months for axitinib; 4.6 vs. 2.9 months for sorafenib), although these data are to be regarded as hypothesis-generating given the retrospective nature and small subsets with overlapping CIs [30]. Upcoming trials of sequential therapy may reflect further on this observation.
In the AXIS trial, patient-reported outcomes were assessed by the Functional Assessment of Cancer Therapy Kidney Symptom Index (FKSI) questionnaire, as well as FKSI-Disease Related Symptoms (FKSI-DRS) subscale, at the onset of therapy and then monthly until 28 days after the last drug dose [25]. An analysis of time to deterioration demonstrated 17% reduction in FKSI (P = 0.014) and 16% reduction in FKSI-DRS (P = 0.0203) with axitinib compared with sorafenib. These data suggest that the benefit in PFS gained with axitinib is accompanied by a delay in symptoms of advanced RCC in the second-line setting.
Pharmacodynamics and Pharmacokinetics
Available as 5 mg and 1 mg tablets, axitinib achieves peak plasma concentration in 3 hours after a high-fat, high-calorie meal, and 2 hours after overnight fasting [31]. According to manufacturer's guidelines, it may be taken with or without meals [32]. B.i.d. dosing achieves 1.4-fold greater accumulation compared with once-a-day dosing. With a plasma half-life of 2.5–6.1 hours, steady state is achieved within 2–3 days. The drug is primarily metabolized by cytochrome P450 (CYP) 3A4/5, and to a lesser extent by CYP1A2, CYP2C19, and uridine diphosphate glucuronosyltransferase 1 polypeptide A1 (UGT1A1) [33]. Axitinib is an inhibitor of the efflux transporter P-glycoprotein (P-gp) in vitro, but is not expected to inhibit P-gp at therapeutic plasma concentrations. Axitinib is eliminated by hepatobiliary excretion and phase 1 studies have suggested <1% excretion of the drug in urine [17]. Dose modifications are not recommended for patients with mild hepatic impairment (Child-Pugh A) [34]. While axitinib has not been studied in patients with severe hepatic failure (Child-Pugh C), the starting dose should be reduced by 50% in patients with moderate hepatic failure (Child-Pugh B). The incidence of grade 3–4 transaminitis (defined as aspartate transaminase [AST], alanine aminotransferase [ALT] >5–10-times the upper limit of normal) is <1%; however, baseline and periodic monitoring of AST, ALT, and bilirubin are recommended through the course of treatment for all patients. No starting dose adjustments have been recommended in preexisting mild-to-severe renal impairment, but caution is advised in end-stage renal disease (creatinine clearance <15 mL/min) [32].
Coadministration of axitinib with strong CYP3A4/5 inhibitors (e.g., grapefruit, ketoconazole, itraconazole, clarithromycin, atazanavir) may increase axitinib plasma concentrations. On the other hand, coadministration with strong CYP3A4/5 inducers (e.g., rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, and St. John's Wort) may decrease plasma concentrations [32].
Pharmacodynamic Variability
Investigators recently analyzed single nucleotide polymorphisms (SNPs) in VEGF and related receptors, and their correlation with hypertension and PFS in the phase 3 axitinib AXIS study [35]. Preliminary data suggest that three VEGF-A SNPs revealed potential association between VEGF genotype and PFS. Although these data are preliminary, it is noteworthy that these polymorphisms were not associated with axitinib-related hypertension or diastolic hypertension [35]. Additionally, a meta-analysis of pooled data from 11 axitinib studies has not revealed a significant association linking gene polymorphism for enzymes CYP3A4/5, CYP1A2, CYP2C19, UGT1A1, and P-gp to variations in axitinib pharmacokinetics [36]. Additional investigation into pharmacogenomics as they relate to axitinib efficacy and toxicity is needed.
Dose Escalation
In the AXIS trial, dose escalation of axitinib was permitted based on physician discretion in patients without hypertension (defined as blood pressure ≥150/90 mmHg), absence of toxicities more than grade 2 (by Common Terminology Criteria for Adverse Events [CTCAE] version 3.0), and absence of the use of antihypertensive agents. In patients satisfying these criteria, dose escalation was allowed from 5 to 7 mg b.i.d. after 2 weeks. Additionally, dose escalation was permitted in another 2 weeks to 10 mg b.i.d. in patients who continued to satisfy the above criteria, with additional provision for dose reduction in cases of adverse toxicities and physician discretion used throughout [25].
Results of a secondary analysis did not reveal a significant difference in median PFS among patients who received daily doses of axitinib ≤10 mg compared with patients receiving higher doses of axitinib, with both groups having better PFS than the sorafenib arm [30]. This result is to be expected on the basis of axitinib pharmacokinetics. That is, patients who tolerated the 5 mg b.i.d. standard starting dose may have subtherapeutic axitinib drug levels. Dose escalation to 7 or 10 mg b.i.d. elevates axitinib drug levels in those patients to above threshold, comparable to patients who do experience hypertension or other toxicity at 5 mg b.i.d. Thus, dose titration with axitinib normalizes blood levels in a subset of patients, allowing them to achieve therapeutic axitinib levels and, thus, an antitumor effect. Given interpatient variability in the ability to achieve therapeutic plasma drug levels, dose escalation of axitinib is critical for optimal administration, as is true for many, if not all oral agents.
Enrollment for a randomized phase 2 study to evaluate efficacy of front-line axitinib with dose titration in 200 treatment-naive patients has been completed [37]. In this study, after 4 weeks of standard dosing (5 mg b.i.d.), eligible patients were randomized to a dose titration arm (standard dose plus escalating doses of axitinib, arm A) versus standard dose and escalating doses of placebo (arm B). Eligibility for dose titration was based on absence of hypertension (>150/90 mmHg), grade 3 or 4 toxicities, prior dose reduction, and use of more than two antihypertensive agents. Patients not meeting randomization criteria for dose titration continued on standard dosing in a third arm (arm C). Preliminary analysis performed in a subpopulation that had pharmacokinetic assessments on day 15 of cycle 1 indicated that patients with drug exposure above the therapeutic threshold (area under the plasma concentration time curve from 0–12 h [AUC0–12] ≥150 ng/mL) on day 15 of cycle 1 had a longer median PFS and higher ORR than those with subtherapeutic exposure (median PFS: 13.9 months vs. 8.3 months; ORR: 59% vs. 48%). In a blinded pooled analysis of the entire enrolled population, ORR in arm C was higher (56.0%; 95% CI 45.2–66.4%) compared with arms A+B (40.2%; 95% CI 31.0–49.9). These data suggest that response rates and PFS more likely depend on achievement of therapeutic concentration of axitinib, rather than specific drug dosage. This lends support to consideration of dose escalation to improve treatment response, by optimization of plasma drug levels. The unblinding of this study and comparison of patients eligible for dose titration who underwent dose escalation versus patients who did not, will provide more definitive insight into the clinical utility of dose escalation.
Dose Titration
Currently, the recommended oral starting dose of axitinib is 5 mg b.i.d. Periodic monitoring of blood pressure is recommended. In patients who do not develop dose-limiting toxicity (grade 3 or 4), are normotensive, and are not receiving antihypertensive agents, uptitration to 7 mg b.i.d. 2 weeks after initiation is suggested. Using the same principle, the dose can be increased to a maximum of 10 mg b.i.d. In patients who require dose reduction because of adverse effects, a decrease to 3 mg b.i.d. is recommended. Further dose reduction to 2 mg b.i.d. may be necessary in some cases.
Toxicities and Their Management
Common treatment-emergent all-causality adverse events in the phase 3 AXIS trial
Treatment-emergent events
Axitinib (n= 359)
Sorafenib (n= 355)
All grades
≥ Grade 3
All grades
≥ Grade 3
Adverse events
197 (55)
38 (11)
189 (53)
26 (7)
145 (40)
56 (16)
103 (29)
39 (11)
140 (39)
41 (11)
112 (32)
18 (5)
Decreased appetite
123 (34)
18 (5)
101 (29)
13 (4)
116 (32)
9 (3)
77 (22)
4 (1)
111 (31)
48 (14)
Palmar-plantar erythrodysesthesia
98 (27)
18 (5)
181 (51)
57 (16)
Weight decreased
89 (25)
8 (2)
74 (21)
5 (1)
85 (24)
12 (3)
61 (17)
3 (1)
74 (21)
19 (5)
50 (14)
9 (3)
73 (20)
4 (1)
72 (20)
3 (1)
69 (19)
1 (<1)
29 (8)
55 (15)
3 (1)
59 (17)
2 (1)
Mucosal inflammation
55 (15)
5 (1)
44 (12)
2 (1)
54 (15)
5 (1)
39 (11)
5 (1)
54 (15)
5 (1)
44 (12)
1 (<1)
45 (13)
1 (<1)
112 (32)
14 (4)
14 (4)
115 (32)
Laboratory abnormalitiesa
113/320 (35)
1/320 (<1)
165/316 (52)
12/316 (4)
Hemoglobin elevation
31/320 (10)
3/316 (1)
19/316 (6)
2/316 (1)
26/308 (8)
2/308 (1)
48/312 (15)
1/312 (<1)
44/310 (14)
106/317 (33)
10/317 (3)
111/309 (36)
11/309 (4)
Creatinine elevation
185/336 (55)
131/318 (41)
1/318 (<1)
43/336 (13)
6/336 (2)
158/318 (50)
51/318 (16)
19/336 (6)
5/319 (2)
132/336 (39)
4/336 (1)
188/319 (59)
5/319 (2)
Lipase elevation
91/338 (27)
16/338 (5)
148/319 (46)
47/319 (15)
Instructions to include in patient information packet for axitinib
• Treatment information regarding axitinib drug formulation and dosing.
• Information regarding possible food and drug interactions, and other precautions to consider with axitinib therapy.
• Possible side effects, prevention, and early management strategies. This should include a discussion regarding which side effects may be prevented or less severe with prophylactic management (i.e., initiation of oral and skin care regimens prior to initiation of treatment).
• Contact information for their nurse, oncologist, and other healthcare team members, including who (and how) to contact when the office is closed. Emphasize the importance of early communication with the nurse/oncologist as side effects develop.
• Specific instructions regarding home monitoring of blood pressure.
• Daily log to record the day, dose, and time of drug administration, along with space to document side effects and blood pressure measurements.
Hypertension should be controlled prior to the initiation of therapy. Home blood pressure assessments should be individualized based on the patient's medical history, concomitant medications, and drug therapy. Patients with a history of hypertension, cardiac co-morbidities, renal dysfunction, or diabetes should be closely monitored for treatment-induced hypertension [39]. Early awareness of changes in home blood pressure assessments allows the clinician to begin or adjust antihypertensive medications, improve control of hypertension, and minimize the patient's risk of developing hypertension-related toxicity.
Management of axitinib-associated gastrointestinal side effects includes dietary and medication interventions. Information about dietary management of diarrhea should be given to the patient prior to the initiation of therapy, including consumption of bananas and rice, and the avoidance of spicy foods. Pharmacologic interventions include loperamide, diphenoxylate hydrochloride/atropine sulfate, tincture of opium, probiotics, and psyllium fiber supplements [40]. Avoiding caffeinated beverages and increasing fluid intake can decrease the potential for diarrhea, dehydration, and renal dysfunction. Frequent meals, increasing calorie intake, nutritional supplements, and consultation with a nutritionist can minimize the negative impact of anorexia.
Hand-foot syndrome is a class effect of VEGF-TKIs, and requires ongoing assessment and management to control the extent and severity of this adverse event. Assessment of skin condition and noting the presence of calluses or structural abnormalities that increase pressure on bony prominences should be done at baseline, at each clinic visit, and discussed during phone assessments thereafter. Instructions regarding proactive skin care and supportive footwear should be provided at baseline, with ongoing evaluation and adjustment of interventions throughout treatment. The "3C" approach to management of hand-foot syndrome includes controlling calluses, comforting with cushions, and covering with creams, and provides an easy-to-remember method for patient education and intervention strategies [41, 42].
Treatment modification including interruption and dose modification may be required in spite of effective patient education, proactive strategies, and frequent and ongoing communication to adjust interventions for drug-related side effects. Interventions directed at fatigue include energy conservation, activity enhancement, psychosocial and nutritional interventions, and psychostimulants after ruling out other causes of fatigue [43]. Hypothyroidism is also associated with the increased incidence of fatigue, emphasizing the importance of obtaining baseline and ongoing thyroid function testing [38, 43]. Hypothyroidism with VEGFR inhibitors may result from inhibition of angiogenesis around the thyroid gland. Thus, periodic monitoring of thyroid function is recommended.
Hypertension as a Biomarker
Importantly, treatment of hypertension itself is not expected to affect antitumor activity [15]; thus, axitinib-induced hypertension should be aggressively managed with standard antihypertensives. Additionally, preliminary subset analysis of the phase 2 front-line study of axitinib with dose escalation has suggested that patients with mean increases of diastolic blood pressure at , day 15 of cycle 1 compared with baseline (ΔdBP) ≥15 mmHg have a higher ORR than ΔdBP <15 mmHg (61% vs. 53%) [37].
In conclusion, axitinib has expanded available options for mRCC patients. Selective inhibition of the VEGFR-1, 2, and 3 at clinically applicable concentrations and biochemical potency against VEGFR contribute to its clinical efficacy. Prolonged median PFS is achievable compared with an active comparator in refractory patients, and is currently being evaluated in the front-line setting in mRCC. Analysis of patient-reported outcomes also suggests a delay in symptoms in patients with advanced RCC. Overall, the major dose-limiting adverse effects of axitinib include hypertension, diarrhea, and fatigue. Importantly, hypertension may be a useful biomarker of drug efficacy. Dose escalation is of considerable interest and is undergoing further evaluation in phase 2 studies. Ongoing phase 3 studies are also assessing the role of axitinib in the front-line setting [46], as well as adjuvant treatment in high-risk patients [47].
Prior to peer review, Pfizer was offered the opportunity to review this paper for scientific accuracy. No writing assistance, other editorial involvement, or financial support was provided by the manufacturer in the production of this manuscript. This article does not necessarily reflect the opinions, policies, or recommendations of Pfizer or any of its employees. Dr. Rini is the guarantor for this article, and takes responsibility for the integrity of the work as a whole.
Conflict of Interest. Dr. Mittal has no personal, commercial, academic, or other financial interests to disclose. Laura Wood has an honorarium for speaker bureau participation from Pfizer. Dr. Rini has consulting and research funding from Pfizer.
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 source are credited.
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|FirstOntario Credit Union
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- Product Description
- Specification
- Shipping Options
- Reviews
Disco Ball Mirror.
Add a touch of disco into your interiors with the Disco Ball Mirror, exclusive to PAGAZZI Lighting. It features a curved frame with mirrored mosaic pieces in the style of a disco ball. Ideal for creating the illusion of having more space in your interiors.
- PAGAZZI Exclusive.
- Mosaic Round Frame.
- Wall Mounted.
It measures 820mm in diameter and projects 65mm from the wall.
Additional Information
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Orders of £50 and over qualify for free next day UK Mainland delivery* with DPD.
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The UK healthcare industry covers a wide range of legal disciplines and within it, several can usually be counted on to be busy in terms of recruitment.
According to Jonathan Smyth, a consultant at DMJ Legal, there is at present the usual demand for defendant clinical negligence lawyers, particularly within the London market, mostly at the two-to-five PQE level.
"This has continued at a steady level over the past few years owing to the relatively small number of firms with an offering in this area within the London market," adds Smyth. "We have also seen a rise in demand for lawyers with experience in healthcare regulatory work, particularly those with knowledge and experience of defending medical practitioners against regulatory investigations. Mental health remains a watching brief for
a number of the specialist healthcare practices within the London market, given the rarity of experienced lawyers within this niche sector."
The level of experience that firms are typically recruiting for at the moment depends on the legal discipline within this sector, although Smyth says the majority of the firms looking to hire are focusing their attention on junior to mid-level lawyers, again primarily those at the two-to-five PQE level.
"Senior individuals are also of interest," adds Smyth, "although we have seen one or two NQ roles appearing in the past few months."
Healthcare can certainly be an area of opportunity for lawyers looking to make the move in-house, with the most obvious option for those with experience
of the sector being a position with one of the regulators such as the General Medical Council, General Dental Council or Nursing and Midwifery Council.
There are also options within certain NHS trusts, says Smyth.
"Those with experience in more commercial disciplines with a healthcare focus in their client base may also consider in-house opportunities with private healthcare providers and insurers, however these
have not been particularly forthcoming and are usually heavily over-subscribed in terms of applications," he says.
In terms of other recruitment trends in the healthcare sector, Smyth says that although the recent reforms in the NHS, such as the merger of PCTs, might on the face of it look like they would create even more of a burden on budgets and staffing needs, they have actually contributed to an increase in headcount across a number of private practice firms with a healthcare focus.
"Healthcare firms are also finding themselves beginning to increase their headcount in areas that were not as prominent for them before, such as competition law," he concludes.
At many levels. healthcare is one of the toughest sectors out there, but clearly there are opportunities for the right candidates.


text:
Venezuelan Pastor Maldonado of Williams secured a victory against Fernando Alonso of Ferrari at the Spanish Grand Prix at Barcelona's Catalunya track. This first win for Maldonado ends the losing streak that Williams has been on since the 2004 season. Maldonado and Alonso were head to head until the final laps but Williams' man was able to draw away and win.
To get second place, Alonso had to contend with Lotus' Kimi Raikkonen. At the first corner of the race, Alonso quickly took the lead as he raced past Maldonado. Alonso then got a three-second lead in the first stint as both had a substantial lead over the others in the field. Maldonado had a brilliant out-lap while Alonso fell behind Charles Pic's Marussia on his in-lap, resulting to Williams getting the advantage over Ferrari at the second pitstops.
Maldonado sped away for some laps until he got a 7s lead. Alonso began to come back at Maldonado, raising the gap to 4.2s before Williams had a somewhat slow final pitstop with a left-rear incident.
Raikkonnen was a few laps behind the two leaders, who had to make sure that their tires stayed intact as they kept up with the other. There were a few moments when it seemed that Maldonado would give way to Alonso's pressure but it turned out to be Ferrari that began to lose pace in the final stages. The lead gap started to widen again. Eventually, Maldonado scored a win with a 3.1s lead.


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RevoStock Tech Blotches 52839
After Effects Project \ Commercials \ Intros \ Opening Sequences \ Credits
After Effects Project - Tech Blotches 52839 by Digital_Spatula @ RevoStock
After Effects Project \ Commercials \ Intros \ Opening Sequences \ Credits
Sound: no; Loopable: no; Downloads: 20; Model Release: no.
This product is an Adobe After Effects project file. It requires Adobe After Effects version 7.0 or higher as well as any plug-ins listed fellow: Required After Effects Plugins: None
Grunge-style design with 3D camera moving around to different frames of content. Cool organic flashed help the edgy look. All content is easily customizable. SD version is also included.
Keywords: grunge 3D camera rough edgy organic grunge 3D camera rough edgy organic.


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Kentucky working to update missing persons cases
LOUISVILLE, Ky. (AP) -- Dr. Emily Craig has more than 40 people in her care and she has no idea who any of them are.
But she's determined to find out.
The people—in the form of unidentified remains—were found around Kentucky going back as far as 1973.
Craig, Kentucky's state forensic anthropologist, is using new technology to extract DNA samples and has ordered new facial reconstructions on all the remains in hopes of identifying them.
"We're doing as many cold cases as possible," Craig said, who has new facial reconstructions done on eight of the remains and DNA samples from about half of them.
The information is being fed into the FBI's national DNA database for missing persons at the University of North Texas Health Science Center, she said. That database, part of the President's DNA Initiative, is aimed at eventually linking all missing persons databases in all 50 states to make it easier to identify remains when they are found.
There are about 5,000 unidentified missing persons reported at any time in the United States, said George Adams, program manager for missing persons at the Texas center.
The center prioritizes its cases, first handling active investigations into missing children, then older cases involving missing children, then investigations involving missing adults, Adams said.
The lab currently has DNA samples from about 400 cases, including about two dozen from Kentucky, Adams said. Finding DNA matches is key to solving the mystery surrounding what happened to the person, he said.
"The longer remains stay unidentified, the longer it is before police agencies can start their investigation."
Adams, a former Fort Worth, Texas, police officer, said the longer it takes to get investigations started, the tougher they are to solve because bodies and evidence deteriorate, memories fade and witnesses get harder to find.
Craig's work proved to be the key to solving a 12-year-old Kentucky case of unidentified remains known as "Madison Man."
The case was one of Craig's first efforts at updating facial reconstructions and DNA samples. Once the reconstruction of "Madison Man" was done, Craig had it posted online.
Family members saw it and eventually provided DNA samples that matched samples taken from the remains. Thus, Craig was able to identify Douglas Martin Prouty, 36, of Madison, Wis., who was found by hikers on Thanksgiving Day 1993 near Berea College.
Tanya Dolske, founder of Wisconsin Advocates for Families of Missing People, said Prouty could have been identified shortly after he was reported missing if adults took a higher priority with law enforcement. Investigators should have pushed harder to have a new facial reconstruction done of Prouty and had his DNA put into the national database sooner, Dolske said.
"It's the perfect example of what can happen if things are not done," Dolske said.
Kentucky State Police Lt. Mark Merriman, who began reinvestigating the "Madison Man" case three years ago, said everything that could have been done using older technology had been done when he took over the case. A second facial reconstruction was done because newer techniques were available and it was worth taking a chance, Merriman said.
"We thought the case was solvable," he said.
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Highs and Lows episode 1 part 1
Published by fisherprice1 in the blog fisherprice1's blog. Views: 58
Highs and Lows
"Pilot" Part 1
*In the opening scene, Chris is franticly running around the apartment getting ready for work. He overslept is scared he is going to be late. Chris's roommate Tyler is lying on the couch watching television.
Tyler: Chris! Stop being so loud! I am trying to watch The Hannah Montana.
Chris: You know man, it kind of creeps me out that you watch that.
Tyler: She is 18 now, so it's ok.
Chris: Whatever Tye, how long have you been awake?
Tyler: Awake? Dude I haven't even gone to bed. I didn't leave the party last night until 5 this morning. Everyone was there!
Chris: I wasn't there.
Tyler: Maybe it's because you were hammered off your ass and throwing up everywhere by 11 o'clock last time? Kyle's apartment will probably never smell the same again!
Chris: If that's the worst thing that ever happens to the guy, I think he will be ok. Anyways why didn't you wake me up? I have to be at work in 20 minutes!
Tyler: I didn't want to wake you up. You looked so peaceful, plus it's fun to watch you spas and freak out….kind of like you're doing now.
Chris: You do realize that you have to be at work at 9 also, right?
Tyler: Yeah I do, but who cares. I can get away with anything at that place. You know this.
Chris: Unfortunately I do. How you are still employed at the place completely baffles me. I work twice as hard as you do and 90% of the time you get all the credit. How does that happen?
Tyler: What can I say? I'm always at the right place, at the right time. I'm just lucky!
Chris: Yeah, well sooner or later your luck is going to run out. I'll see you there.
*Chris runs outside and tries to start his car, but to no avail. He then runs back into the apartment.
Chris: Dude, get up and get dressed! You're going to have to drive us both to work. My car won't start.
Tyler: Chris you don't understand. If I show up to work on time today, then they are going to expect me to do it again tomorrow.
Chris: I have a perfect attendance record. You are not going to ruin that! Come on!
Tyler: Call a cab bro. I guarantee you he will get you there before my ass shows up.
Chris: You really are a complete lazy ass and never helpful! You know that?
Tyler: It didn't bother me when my mom, dad, brother, sister, grandma, grandpa, other grandma, other grandpa, and all my ex-girlfriends told me that……so it's not going to bother me when you say it. But thank you for your honesty, it is much appreciated.
*The next scene is outside the apartment complex. Chris called for a cab and is waiting for it. The cab eventually pulls up.
Cab Driver: Where to kid?
Chris: Good morning sir, how are you?
Cab Driver: Well I'm tired because I haven't slept in 2 days, I'm sexually frustrated because my wife is a complete whore and sleeps with every man in town but me, and I had my middle finger chopped off because I couldn't pay my "provider" for the "stuff" that I got from him.
Chris: A simple "not good" would have done me just fine. To the Beat Brakes Mall please and step on it. I am running very late. Car trouble comes at the worst possible time, you know? So why haven't you slept in two days?
Cab Driver: Well when a "provider" breaks into your house in the middle of the night and chops off your middle finger, you tend to not sleep very well the next couple of nights. If my wife wasn't such a whore and actually slept with her husband every once in a while, I wouldn't have to turn to "stuff" to help me deal with my frustration! You get where I am coming from kid?
Chris: I can't say that I do sir, haha….(Chris mumbles under his breath) I hate my life.
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PRIMITIVE ANTIQUE VINTAGE OLD STYLE one of a kind CRATE SIGN- Description FREE SHIPPING!!!!
UP FOR SALE is a one of a kind sign made by me from crate wood. I have printed out the graphic and then secured it to the sign wood. I have then sanded the sign and aged the graphic it to give it a worn, vintage look! I have gotten so many wonderful feedback words on my signs and pillow tucks. Please check it out! For indoor use only.
It would be darling in any primitive or vintage setting. It measures approximately 11 by 5.5". I have several of these available, but the wood pieces are all different so none are identical if purchasing more than one. The sign is absolutely adorable for gift giving or keeping for yourself. Darling conversation piece for any room!
Please view my other signs up for auction!
I will be making many new images on signs over the next few months, so please check back often.
PROPS IN PHOTO NOT INCLUDED. Sign is offered alone for sale.
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Pak Suzuki Family Day 2016
Pak Suzuki Family members celebrated Family Day on 3rd September, 2016 at PAF Museum Karachi with a theme rightly incorporated in its slogan "Together we are, Together we will". The family day was organized with the prime objective to enhance the motivation level and affiliation of the employees with the organization by providing them an opportunity to enjoy and celebrate with their families. Family day was started by presenting the specially made souvenirs to the guest at their arrival.
Long Service Appreciation
A Small ceremony for long service appreciation was held at the event for those employees who have served Pak Suzuki for 15 years or more. These members were appreciated by awarding them souvenirs for their long affiliation with Pak Suzuki.


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PP 159 Lahore-XXIII/ PP-159 Pakistan
PP 159 is a constituency for the seat of Punjab's Provincial Assembly for Lahore District. Lahore is Capital of Punjab Province and play main role in Provincial politics. Lahore District has largest number of seats in Provincial Assembly of Punjab. There are total 25 seats of Lahore in Provincial Assembly and PP-159 Lahore-23 is 23rd of these 25 seats.
This consistency consist of Kahna Town, some areas of Raiwind and Guru Mangat.
PP 159 Lahore-XXIII Important Localities & Areas
- Guru Mangat
- Kahna Nau
- Lakheke
- Jahman
- Ladheke
- Saraieh
PP 159 Lahore-XXIII Town Committees/ Municipal Committees/ Qanungo Halqas/ Tehsils/ Patwar Circles/ Census Charges
- Kahna Town Committee
Heer Qanungo Halqa excluding following Patwar Circles;
- Karbath
- Ladher
- Harpalke
- Noorpur
- Ghowing
- Khana Qanungo Halqa excluding some Patwar Circles
Following Patwar Circles of Raiwind Qanungo Halqa;
- Ghang Sharif
- Ladhe Ke Nevian
- Ledhe Ke Uch
PP 159 Lahore-XXIII Population Statistics
- Male Voters – 77502
- Female Voters- 63968
- Total- 141470


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Snopes.com is a pretty neat site that investigates the validity of commonly believed stories. The baseball section exposes some urban legends that you might find interesting. In fact, the whole site is pretty interesting. Be sure to read the key explaining the colored balls and to click on the underlined words on each story to read the complete story.
Be sure to read the Charlie Dressen story.


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Senior leaders spent months in Delhi for tickets leaving field open for BJP: Digvijaya Singh
Why was there such a huge setback for Congress?
I had campaigned extensively in Madhya Pradesh and Chhattisgarh. The election results have astonished me. I could see anger in the eyes of the people against BJP state governments.
I thought any Congress candidate who could channelise the anger would win. My own assessment was that Congress could win up to 110 seats in MP. I have never been so off the mark, politically.
What do you say to the charge that senior Congress leaders in poll-bound states were not united?
I don't agree with such talks. All senior leaders, especially in Madhya Pradesh, worked together and campaigned as a team. But there have been some strategic lapses. For example, all senior leaders spent around one-and half months before polls in discussions in Delhi to finalise candidates.
It left the field open for BJP to consolidate. Similarly, ticket aspirants were busy lobbying in Delhi or Bhopal or other state capitals when they should have been campaigning.
In the process the Antony Committee proposal to announce Congress candidates well in advance was overlooked. Elections are mainly fought at booth level, with mobilisation from panchayat level onwards. Since Congress is not a cadre-based party, it was for candidates to entirely mobilise campaign plans.
Since most candidates were announced just before the last date of nominations, there was not much time for them to get their act together. I think, Congress should start declaring candidates for the Lok Sabha polls right away.
Where does this setback leave the party?
As the Congress president underlined, we need to do deep introspection within the party and draw our strategy for the Lok Sabha elections. The emergence of the Aam Aadmi Party is a positive indication for our democracy.
It also reflects the disenchantment ordinary people have with the political class and their growing frustration with many negative aspects of power politics. I think all major political parties must read the message right and reposition.
What is your assessment about Rahul Gandhi's style and methods of functioning?
Rahul Gandhiji wants the functioning of Congress changed dramatically, to which the party is not responding at the pace he would like it to.
You have now heard him saying he would work harder and more aggressively to change ways of Congress organisation and make it reflect voices and aspirations of the common man. He also wants to bring more transparency in Congress organizations, which he has done in the working of NSUI and Youth Congress.
Will Congress adopt Sonia Gandhi model or Rahul Gandhi model in the run up to the Lok Saba elections?
I don't see it as a 'Rahul model' or 'Sonia Gandhi model'. Rahul Gandhiji has some new ideas and he has his own vision for the new India and aspirations of the new generation.
We have to incorporate this in the party and channelise it in the party's functioning and campaigns. Soniaji is the leader who has to guide the party and ensure that whatever is the strategy, it is implemented and followed by all.
Do you think BJP victories in four states would boost the standing of its prime ministerial candidate Narendra Modi?
Modi is the face of BJP for the LS polls. He has been the CM of Gujarat for 11 years. But now he has to spell out what kind of a vision he has for India.
So far, Modi has been only criticising Congress and finding faults with everything that the UPA government does. But as a nation, we are yet to hear what is his alternative vision for India. As far as election results are concerned, I think Modi has only only addressed many rallies in all states.
Shivraj Singh Chouhan, Raman Singh and Vasundhara Raje led the BJP campaign in their respective states, using traditional BJP machinery, and led their party to victories. Will Congress try to prop up a larger coalition to take on NDA in the LS polls?
I think assembly elections were mainly fought on local and state issues. The Lok Sabha elections are bound to be a different ballgame. It was during 2004 elections, Congress did some strategic alliances. I am sure the Antony Committee will look into this aspect for the upcoming Lok Sabha elections.


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MOVIE SYNOPSIS [ General Audiences ] Directed by Joshua Hoareau, Tatiana Barrie heads the cast of this movie of Australia, with dialogues in English, whose official premiere was scheduled for 2014. You can watch Peacekeeper online on TV cable or theaters with original audio in English at different dates. This film premiered in theaters in 2014.
Rating: 5 by 8 users./
Runtime: 11 minutes
Tatiana Barrie, Addam Bramich, Lliam Murphy, Paul O'Brien, James Schaw, Ben Steel and Roger Wilson.
Short film, Drama, War.
11-minute film (full movie) directed by Joshua Hoareau.
The original audio of Peacekeeper has dialogues in Dolby Digital, it was produced in Australia.
It premiered in cinemas or television in 2014.
Screenplay written by Oliver Quinn, Jay Mains, Michael Sarlo and Joshua Hoareau.
Joshua Hoareau.
Joshua Hoareau, Jay Mains and Rick Grzyb.
This film was produced and / or financed by CineStudios.
Composed by Richard Labrooy.
Without commercial breaks, the full movie Peacekeeper has a duration of 11 minutes; the official trailer can be watched in streaming on the Internet. You can watch this full movie free in EnglishDolby Digital in movie TV channels, renting the DVD or with VoD services (Video On Demand player, Hulu) and PPV (Pay Per View, Netflix).
See the page of this full movie, Peacekeeper in FULLTV Movies.


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The new Olympic Channel brings you news, highlights, exclusive behind the scenes, live events and original programming, 24 hours a day, 365 days per year.
One of the IOC's roles is to encourage the promotion of ethics and good governance in the sports movement.
With this aim, the IOC has established in the first place the Ethics Commission, elected by the IOC Session. This body defines the Code of Ethics and, in case of violation of the ethics principles, investigates complaints and proposes sanctions.
In 2015, as recommended in the Olympic Agenda 2020, the IOC created the position of Chief Ethics and Compliance Officer, whose mission is to assure compliance with ethical principles and good governance.
Finally, the Ethics and Compliance Office fulfills a mission of prevention and monitoring related to risks of manipulation of competitions . One of the measures implemented is the IOC Integrity and Compliance Hotline, which allows reporting infringements of the Code of Ethics.
The IOC Code of Ethics is based upon the values and principles enshrined in the Olympic Charter, of which it forms an integral part. The Code is defined and updated by the IOC Ethics Commission.
The IOC's ultimate goal is to protect clean athletes. We are therefore actively committed to fighting all forms of cheating in sport.


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Go check out Ann's Blog page,
Yall need to swoosh on over and download this amazing app! It's all about Thanks and Giving and it's free for Thanksgiving! Who wouldn't like an easy way to express their blessings and gratitude in an easy app?
If you haven't heard of Ann Voskamp, you better look out cause she's AMAZING! Her book is undeniably heart wrenching and heart warming simultaneously. You will be challenged, astounded, blessed, lifted up, and changed after reading her book. Go check it out!


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Michael Kors Hamilton Traveler Large Leather Satchel
$398.00 Actual transaction amount
Hamilton Traveler Large Leather Satchel is a sophisticated tote that is slightly structured with a relaxed feel making this perfect for everyday. Featuring top zip closure, adjustable leather shoulder strap, rolled top handles with rings, protective metal feet and frame top with signature engraved lock and hanging tab hidden key. Gold tone signature hardware and detail. Signature dust bag included.
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$398.00 Actual transaction amount
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Not for the fainthearted, Badass is the ultimate workout for your derriere. Be prepared to lift, squeeze and burn your way through this glute and leg workout….Get your ass Read moreView
Bunny Bootcamp
From fierce choreography to the ultimate in toning techniques, Bunny Bootcamp is a high intensity cardio & conditioning class. The workout is designed to help women achieve th Read moreView
A full body cardio workout that gets you to kick, punch, knee and elbow the freestanding bags. Music played loud with a heavy baseline to keep the arms and legs pumping. BYO b Read moreView
Pound is a full-body cardio jam session, combining light resistance with constant simulated drumming. The workout fuses cardio, Pilates, isometric movements, plyometrics an Read moreView
Thigh High
Whatever you're wearing, toned inner thighs will help you rock your look. Keep your pins in shape with this toning lower body workout, be prepared to lift, squeeze, tone and t Read moreView


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Gerhard Herzberg
Life Path Number 6
Gerhard Herzberg is a male celebrity.
He was born on Sunday December 25th 1904, in Hamburg, Germany,.
Gerhard Herzberg possesses great compassion and seeks to be of service to others. He has concern for the weak and the downtrodden. He a healer and a helper to others. Gerhard is capable of giving comfort to those in need and will frequently offer a shoulder for others to cry on.
Herzberg's task in life is to develop the tools necessary to be truly helpful to others, rather than to simply be a sympathetic ear. Gerhard Herzberg must find the balance between help and interference. In the same way, he must learn the delicate art of the counselor who knows when to leave the struggle to others and when to avoid taking away the necessary experiences and lessons of life.
Gerhard Herzberg is naturally balanced. Therefore, he is well equipped to support and ground others in times of trial.
It is in his nature to take on responsibility - often filling the void left by others - and to not turn away from personal sacrifice. At times, Gerhard Herzberg may feel overburdened by the travails of others. However, the love others bestow upon him is his well deserved reward.
Gerhard tries to maintain harmony within the family or group, balancing and fusing divergent forces. He seeks marriage and is often a wonderful parent, offering warmth, protection, and understanding to children.
He is generous, kind, and attractive. Herzberg is often admired even adored which baffles him. He is humble and yet he carries a deep pride. Gerhard Herzberg moves well and gracefully, but will have to work to stay in shape. He must seek out physical exercise and limit the sweets and dairy he craves to keep himself from becoming plump and round.
When young, Gerhard must be careful not to choose partners for the wrong reasons, and to not let sentimentality influence his decision, especially those involving the choice of a spouse. Herzberg needs to be needed, but must learn to discriminate between those he can help and others who are made weaker by his care. After all, it is in Gerhard's nature to be attracted to the weaker brothers and sisters among us.
The temptation and the danger for Gerhard Herzberg is to think of himself as the savior of the world, carrying the burdens of others on his shoulders.
Gerhard Herzberg is blessed with musical talent, as well as in the visual and performing arts. However, his creativity may well be suppressed due to his willingness to sacrifice, or his inability to fully appreciate his own talents. This is not to say that Gerhard cannot excel in these areas; on the contrary, he has the talent, and with effort he can make a success in a number of artistic fields.
Herzberg also has enormous talent in business. He is blessed with a great deal of charm and charisma, which Gerhard Herzberg uses effectively to attract the people and support he needs.
You and Gerhard
About Gerhard's Life Path number
If ever there was a single moment of total transformation, it was actually the moment of Gerhard Herzberg's birth. In that instant, Gerhard stepped through a door in time into a new reality - the reality of human life. The most critical number in Herzberg's numerology chart is based on the date of his birth - the moment when the curtain went up in Gerhard Herzberg's life.
Read more about our numerological interpretation of Gerhard Herzberg's


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Shortly after the announcement of the passing of an MMA superstar in Kimbo Slice, tributes began to pour out over social media. One such tribute came from his former employer, the UFC, who released this statement.
UFC is saddened to learn of the passing of Kevin Ferguson, known to fans around the world as Kimbo Slice.
Slice will forever be a part of UFC history as a contestant on season 10 of The Ultimate Fighter in 2009, and for having fought twice inside the Octagon at The Ultimate Fighter Finale and UFC 113. He carried himself as a true professional during his time in our organization.
While he will never be forgotten for his fighting style and transcendent image, Slice will also be remembered for his warm personality and commitment to his family and friends.
UFC offers its sincere condolences to Slice's family, friends and teammates at American Top Team.
Slice, who only fought for the UFC twice (not counting his TUF bouts) was famous for filming his street fighting antics.
He won his last two bouts in Bellator, but the most recent win was overturned due to a failed drug test. He left MMA with a 5-2 record.
UFC President Dana White also Instagramed a tribute to Slice.
Slice was set to headline Bellator 158 in London next month. Now the ticket link is replaced with a statement from Bellator, which Champions.co reported on yesterday.
No cause of death has been released yet.


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Cadillac Of South Charlotte Body Shop
Featured Business
ABRA Glass Charlotte10421 S Tryon St.
Charlotte, NC 28273
4.2 miles away
"John said they were excellent."
Review for Cadillac Of South Charlotte Body Shop
Bobby W. on 09/20/2014
Bobby said this business provides excellent work. They are very professional and have timely service.
Category: Collision
Service Date: 09/16/2014
Review Created: 09/20/2014
This review was collected via phone interview by Customer Research Inc.


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Trevor Hicks, Advisor Engineer, Naval Nuclear Laboratory
Jessica Coughlin, Principal Engineer, Naval Nuclear Laboratory
The Naval Nuclear Laboratory (NNL) is working on the design and development of standard test articles to support the qualification of metal Additive Manufacturing (AM) procedures and to accumulate material property data based on material, process parameters, specimen orientation, specimen location, and post-processing. The standardization of test articles is an important step in defining requirements for the qualification of additive manufacturing procedures; NNL's efforts are intended to support standards development efforts, such as those of the American Welding Society D20 committee. NNL is in the process of building and evaluating standard test articles for powder bed fusion and directed energy deposition processes. Test article designs and evaluation results to-date will be presented.


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Marbella is a city in Spain that is often called the pearl of Costa del Sol. Those who have visited this city know why – Marbella represents a perfect combination of leisure, pleasure in the sun and natural and manmade beauties. There are many good reasons why this city is one of the most popular holiday destinations in Europe. Long white beaches, amazing clear sea whose colors change from dark green to light blue will make you take dozens of photos while you are there. There are dozens of interesting things to see and do in Marbella, so it is better to make a good plan before you visit this unforgettable city. Our suggestion is to visit some of the hidden gems in it.
We will start with the popular spot Puerto Banus. Many people describe Puerto Banus as the most exclusive and luxurious part of Marbella. The area actually presents the marina/port in this city. This is one of the favorite resorts for golf enthusiasts from Europe too. Puerto Banus possesses very rich cultural and historical heritage. One of the first things that you will notice is the unique and attractive architecture. The area is packed with houses in white and neutral colors, orange trees, clean squares and streets and much more. This is also the place where you can find many exclusive restaurants where you can try some traditional dishes. The cuisine in Marbella is very specific and diverse.
Avenida Julio Iglesia is probably the most famous street in Puerto Banus and it is not unusual to see European and world celebrities walking down this street at any time of the year.
Ralli Museum
MuseoRalli or Ralli Museum is located between the center of Marbella and Puerto Banus. It was founded 15 years ago and has a very rich collection of Latin American art. The works of famous authors like Leopldo Torres Aguero, Wilfredo Lam, Victor Quiroda and Roberto Matta won't leave any visitor disappointed. There are also some works of one of the most popular artists in the world – Salvador Dali.
The Museum of Contemporary Spanish Art
This museum was opened about 25 years ago. The museum contains more than 1000 works by contemporary Spanish author Jose Luis Morales y Marin. He donated his works to the museum. The museum is open at certain periods of the week, so visitors are advised to check the working hours before they visit it.
Selwo Marina
Even though this is a relatively small marine park, it is definitely worth visiting. Most people visit it because of the presence of sea lions and dolphins. There are few different shows that include snakes, fish, lizards, caimans, penguins and other animals.
La Cañada
This is not only the largest shopping mall in Marbella, but also on Costa del Sol. It has more than 150 shops and includes many different famous world brands and local brands.
Marbella is a city that is worth visiting because it has so many different things to offer.


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Boot Tray organizes and keeps all your winter outerwear and footwear in one convenient location. Three-tier organizer stores boots, gloves, hats and scarves. Keeps everything neat and within easy reach; collects melted ice and snow. Bottom shelf: 14-3/4" W x 12-7/8" D; middle shelf: 14-3/4" W x 11-1/4" D; top shelf: 14" W x 9-3/4" D. Stands 27-1/2" overall.
"Great addition to hold boots, shoes, and winter apparatus. Very pleased. Fits very nicely in coat closet." -Customer in Michigan


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Wedding dress
I had a similar negative experience to the customer below. I had sleeves added to my wedding dress and I spent the entire wedding pulling my sleeves back up and having my bridesmaids reattaching my bustle that kept coming undone. I have had friends who have had great experiences here just not me.


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REFOG Terminal Monitor
Visit Publisher Site
REFOG Terminal Monitor Hosting Promo
A surveillance software to monitor employee activities on the Terminal Server, prevent security breaches and control how much time the users spend for work and for fun. Ensuring personnel obedience is the main task of REFOG Terminal Monitor. Tracking and logging what, when and how has been used while connected to the Terminal Server allows administrators manage employees more efficiently.Visit publisher site: REFOG Terminal Monitor
Listing Details
- Version:
- 184.108.40.2067
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Hosted Apps / Security Systems
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- Last Updated:
- Aug 28, 2014
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- REFOG Other listings by this publisher
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- License Type:
- Free Trial
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- Trial period for surveillance software is thirty days, functions are available in that time.
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Words that end in artimes
Found 1 words that end in artimes. Browse our Scrabble Word Finder, Words With Friends cheat dictionary, and WordHub word solver to find words that end with artimes. Or use our Unscramble word solver to find your best possible play! Related: Words containing artimes
- Scrabble
- Words With Friends
- WordHub
- Crossword


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More and more I've been seeing comic creators turning toward YouTube as a way of promoting their comics and teasing upcoming events. Sometimes the commercials are nothing more than a pan or tilt across the comic panel, while others cut the panel up to create a "motion comic." Then there is Dreamkeepers, an indie publication by David Lillie, that created a fully animated commercial.
I'll be honest, and say that watching the bit worked, and I ended up going to the website to find out more about the series. And this brings us to the Major Spoilers Question of the Day:
Do video commercials teasing upcoming issues get you more or less interested in the comic being advertised?
Use the comment section below to share your thoughts.
4 Comments
I think it definitely interest me – especially with the animated commercial, which gives you some pretty tantalizing glimpses of the character design in action. But at the same time, it seems to matter more HOW the commercial is used than WHAT it is. TV commercials are so expensive it's something only the Big 2 can afford (like Marvel's recent AvsX campaign), and I don't know the ad space is really worth it. Viral marketing is a lot more effective – but even more difficult to bank on. So answering your question, they make me more interested in a project, but I don't know if they stir up enough interest to justify the costs of shooting a commercial.
Most comic books commercials usually feel rather bland because they seem to ignore the fact that one media can't be simply ripped from one format and placed into another(Actually they even can, but will serve as nothing more than an image collection). The major point of video ads is that they must give you a sense of tone and scope about the story. And knowing well Dreamkeepers, I can assure that David Lillie achieved that. In a 15 seconds commercial he was able to capture all the essential elements that make dreamkeepers dreamkeepers. And that is what more commercials should do.
I'm against that kind of ad for books because they won't serve as an display of the actual product, since there is no imagery in books. But for graphic novel, go for it guys! As long as you truly display what your work is all about, I'm all for it.
(BTW, not all commercials are expensive. I know for a fact that David Lillie did this commercial by himself in his spare time, on a time space of 2-3 months. No extra fees involved.)
being already interested in it, it made me more exited for later when David Lille gets farther along with it. tv marketing may not work, but internet marketing is what i would suggust he goes for.
I'm certainly going to check this comic. Needs more publicity, though.


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South Africa (404-6) v England
England have made two early breakthroughs on the second morning of the final Test at the Oval, after South Africa resumed on 362-4.
Martin Bicknell took the wickets of Jacques Rudolph and Mark Boucher as South Africa moved on to 404-6.
Bicknell struck in the first full over of the morning when left-hander Rudolph played around a full delivery to be trapped leg before.
And it was two for six from 23 balls for Bicknell when Boucher, who had already edged short of the slip cordon, was adjudged to be caught behind by Alec Stewart, although television replays suggested Boucher had struck his pad.
All-rounder Jacques Kallis steadied South Africa, reaching his half-century from 84 balls, including six fours and a huge six struck off left-arm spinner Ashley Giles in yesterday's final session.


text: Swindon69 Posted May 10, 2012 Oh for the love of God, a new board has taken over and put £200k in to be repaid at £1.5k per month, which isn't too bad. However they've now renegotiated this deal so now it'll be cleared in a year but paying £10k a month. 0 Share this post Link to post Share on other sites


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The return of Eduardo da Silva: Arsenal reserves vs Portsmouth reserves
This is the sight all football fans have been waiting to see since Eduardo da Silva had his leg horrifically broken by Birmingham City's Martin Taylor back in February.
Last night, the Arsenal and Croatian forward returned to action for the first time in ten months to play out the first forty-five minutes in the Gunners' reserve match with Portsmouth. Unfortunately his comeback was not capped with a goal, but the striker showed excellent balance and strength to ride a series of challenges whilst also showing that he retained his eye for goal with several strikes on the target.
Bringing a happy ending to 2008, it is great to see Eduardo back playing football.
Highlights of Eduardo's performance against Pompey can be seen here.


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Fall colors in the city.......... by framafotoWatch
©2013-2017 framafoto
Fall in Gouda.
That's a very pleasant shade of green. Thank you for sharing~
This is beautiful!
awesome colors ^^
Wow, there's so much going on in this! You've done the place justice, actually I am sure it looks much better in your photo than in reality!


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A gentle curling cream that defines, conditions and adds manageability to hair to reveal soft, elongated curls.
Comes in a 340-g pot.
A gentle holding mist that seals in moisture and tames frizz and flyaways to reveal softer and smoother curls.
Comes in a 237-ml spray bottle.
Brilliant conditioning repair cream that intensely moisturises hair, stopping and mending breakage and repairing split ends.
Comes in a 453-g pot.
A gentle curl-activating cream that helps to reveal frizz-free, bouncy curls while delivering volume and shine.
Comes in a 355-ml bottle.
Stimulate hair growth with this powerful tonic featuring an active taurine formula, as a part of an effective anti-hair-loss campaign.
Comes in a 300-ml bottle.
Incredible hair treatment that acts on hair in 10 wonderful ways to deliver beauty, shine, protection and superb condition.
Comes in a travel-friendly 100-ml pump-spray bottle.
Step 2 of an incredible new 2-step system designed to give a fuller look to thinning hair in seconds on both men and women.
Fixing spray will last all day and is proof against sweat, wind and rain. 60-ml bottle.
Step 1 of an incredible new 2-step system designed to give a fuller look to thinning hair in seconds. Works for both men and women.
Fibres come in 6 colours: Black, Dark Brown, Medium Brown, Light Brown, Dark Blonde or Silver Grey.
A complete and effective hair bond treatment kit to protect and optimise hair quality.
Available in expert kit size, which contains 1 x 500-ml bottle of Bond serum and 1 x 500-ml bottle of Sealing mask, or in a trial kit which has 2 x 100-ml bottles of the same.
Silicone-free hair treatment that moisturises, strengthens and smooths to produce beautiful revitalised hair brimming with healthy shine.
Comes in a 150-ml tube.
Revitalise your tools with our professional services
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