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Q: Is there a common practice for updating product pricing from vendors? We have tons of products on our site. The vendors often raise the prices of their product line. If it is something easy like +10% we can easily make this change in the data base. But if the prices are changing chaotically; some up, some down with no common denominator. It can be a hassle keeping track that all the products pricing are up to date with the vendor.
So I was wondering if there is a common practice for this?

A: Ask your vendors to provide a web service that you can call to obtain all the latest product prices. You could then write a service that runs on a regular basis to update the latest prices to your database.

A: John,
it might be an idea to have the prices as a seperate date tracked table, i.e:
prices_xref(product_id, stt_date, end_date, price)

that way you could track the changes 'in time' if need be. of course, if this isn't possible, then another option would be to have a second table that reflected the 'last' prices and do a little compare on that and the live table and report on the differences (in an attempt to identify proces that hadn't yet changed).
of course; many ways to skin the cat :)
jim

A: I'd change the structure of databse by having a price_modifier row there and making the price as some kind of "factory value" (standard value, which then is multiplied by price_modifier). So you just set the percentage (positive or negative) for item and when displaying the actual price on page, do the math for price.


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Cloud Workload Migration optimizes resources and improves efficiency and performance. Understanding what workloads are best moved to the cloud, how to move them efficiently and safely, and managing your assets moving forward is our objective when working with our clients. Simple, safe, secure.


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Biografia
Hanns-Josef Ortheil nasce a Colonia, quinto figlio della bibliotecaria Katharina Ortheil (1913–1996) e del geodeta e poi direttore di banca Josef Ortheil (1907–1988). I genitori persero prima due figli durante la seconda guerra mondiale, poi altri due nei primi anni del dopoguerra. In seguito a questi lutti, la madre era diventata sempre più silenziosa ed infine completamente muta, cosicché Ortheil trascorse i primi anni della sua infanzia con una madre che non parlava e verso i tre anni anche lui divenne per un certo periodo muto. Ortheil imparò quindi a parlare solo a sette anni e lui stesso racconta che la sua prima frase fu: Passalo a me, riferito a un pallone mentre stava giocando con altri due ragazzi. Una prima liberazione da una vita da bambino profondamente introverso e incapace di parlare fu indotta, all'età di quattro anni, dall'inizio delle lezioni di pianoforte, che ricevette in un primo tempo da sua madre. Dal 1956 Ortheil ricevette delle lezioni da pianisti e da maestri di musica. Ortheil fece rapidamente progressi come pianista e volle intraprendere questa carriera come professione.

Una grave e persistente tenosinovite, un'infiammazione che coinvolge la guaina dei tendini dei muscoli flessori della mano, lo costrinsero però a rinunciare a questa prospettiva di carriera, durante una sua permanenza a Roma nei primi anni settanta, mentre studiava al conservatorio e si guadagnava da vivere come organista presso la Chiesa di Santa Maria dell'Anima.

Dopo aver passato i primi anni della sua infanzia e giovinezza a Colonia, Ortheil si diplomò al liceo di Magonza, dopodiché studiò Storia dell'arte a Roma, poi musicologia, filosofia, germanistica e letteratura comparata alle università di Magonza, Göttingen, Parigi e Roma. Durante gli studi universitari negli anni settanta, lavorò come giornalista musicale e cinematografico per il giornale Allgemeine Zeitung di Magonza e negli anni successivi, dagli anni ottanta, come feuilletonista e critico letterario per i giornali Frankfurter Allgemeine Zeitung, Die Zeit, Die Welt, Der Spiegel e Neue Zürcher Zeitung. Nel 1976 conferì il dottorato all'università di Magonza con una dissertazione sulla teoria del romanzo all'epoca della rivoluzione francese.

Dal 1976 al 1982 lavorò in quell'università come consulente scientifico e dal 1982 al 1988 come assistente universitario. Nel 1979 debuttò come scrittore col romanzo Fermer, per il quale ottenne un premio come miglior debuttante della stagione letteraria. Dal 1988 al 1990 esercitò la professione di libero scrittore e nel 1991 ottenne una borsa di studio dall'Accademia Tedesca Villa Massimo di Roma, città in cui da quel momento visse ripetutamente. A Roma Ortheil riprese nel 1993 la sua attività di concertista, suonando sia in privato che in pubblico. Nel 1990 gli fu affidata una docenza di scrittura creativa e letteratura contemporanea nella città di Hildesheim, dove nel 1999 avviò il corso di studi Kreatives Schreiben und Kulturjournalismus (scrittura creativa e giornalismo culturale), dal quale provengono vari scrittori contemporanei. Dal 2003 è professore in questo corso di studi. Nel 2008 è diventato il primo direttore dell'Institut für Literarisches Schreiben und Literaturwissenschaft (Istituto per la scrittura letteraria e scienza della letteratura) dell'università di Hildesheim che si dedica al sostegno di giovani autori sia nella teoria che nella pratica ed alla ricerca in tutti gli aspetti della scrittura. Oltre all'attività didattica presso l'università di Hildesheim, Ortheil è anche docente di poetica presso altre università (Università Washington a Saint Louis e università di Paderborn, Bielefeld, Heidelberg, Zurigo e Bamberga). All'università di Heidelberg Ortheil è professore onorario. Dal 2012 è curatore del Gargonza Arts Award.

Le sue opere sono state tradotte in più di venti lingue.

Opere

Saggi specialistici
 Der poetische Widerstand im Roman. Königstein/Taunus 1980.
 Mozart im Innern seiner Sprachen. Frankfurt am Main 1982.
 Das Glück der Musik – Vom Vergnügen Mozart zu hören. München 2006.
 Wie Romane entstehen. Gemeinsam mit Klaus Siblewski. München 2008.
 Lesehunger. Ein Bücher-Menu in 12 Gängen. München 2009.
 Schreiben dicht am Leben. Notieren und Skizzieren . Duden, Mannheim/Zürich c. 2012, trad. Scrivere idee, Zanichelli, 2012
 Schreiben auf Reisen. Duden, Mannheim/Zürich 2012.
 Die Gegenwärtigkeit des Glaubens. Reflexion zum Text der Kantate BWV 151 "Süsser Trost, mein Jesus kömmt". Anlässlich der Aufführung durch die J. S. Bach-Stiftung am 13. Dezember 2013 in Trogen AR.
 Schreiben über mich selbst. Spielformen des autobiografischen Schreibens. Duden, Berlin/Mannheim/Zürich 2014.

Biografie
 Wilhelm Klemm – Ein Lyriker der "Menschheitsdämmerung". Stuttgart 1979.
 Jean Paul. Reinbek bei Hamburg 1984.

Sceneggiature
 1985: Dämonen der Städte
 1986: Ezra Pound – Ein amerikanischer Hochverräter. (Film per la televisione)

Romanzi storici e saggi autobiografici
 Fermer. Frankfurt am Main 1979.
 Hecke. Frankfurt am Main 1983.
 Köder, Beute und Schatten. Frankfurt am Main 1985.
 Schwerenöter. München u. a. 1987.
 Agenten. München u. a. 1989.
 Schauprozesse. München u. a. 1990.
 Abschied von den Kriegsteilnehmern. München u. a. 1992.
 Römische Sequenz. Rom 1993.
 Familienbande. Paderborn 1994.
 Das Element des Elephanten. München u. a. 1994.
 Blauer Weg. München u. a. 1996.
 Beschreibung: Erwin Wortelkamps Tal bei Hasselbach im Westerwald. Witten 2000.
 Lo und Lu. München 2001.
 Die große Liebe. München 2003.
 Venedig. München 2004.
 Die weißen Inseln der Zeit. München 2004.
 Die geheimen Stunden der Nacht. München 2005.
 Das Verlangen nach Liebe. München 2007.
 Die Erfindung des Lebens . München 2009, trad. Il suono della vita, Keller, 2018
 Rom. Eine Ekstase. Oasen für die Sinne. München 2009.
 Die Moselreise. Roman eines Kindes. München 2010.
 Liebesnähe. Luchterhand, München 2011.
 Das Kind, das nicht fragte. Roman. Luchterhand, München 2012.
 Berlinreise. Luchterhand, München 2014.
 Faustinas Küsse. München 1998.
 Im Licht der Lagune. München 1999.
 Die Nacht des Don Juan. Luchterhand, München 2000.

Premi
 1979: Aspekte-Literaturpreis
 1981: Förderpreis des Landes Nordrhein-Westfalen für Literatur
 1982: Sonderpreis der Lektoren beim Ingeborg-Bachmann-Wettbewerb
 1988: Literaturpreis der Stadt Stuttgart
 1991: Villa-Massimo-Stipendium
 2000: Brandenburgischer Literaturpreis
 2000/2001: Mainzer Stadtschreiber
 2001: Verdienstmedaille des Landes Baden-Württemberg
 2002: Thomas-Mann-Preis
 2004: Georg-K.-Glaser-Preis
 2006: Koblenzer Literaturpreis
 2007: Nicolas-Born-Preis
 2009: Elisabeth-Langgässer-Literaturpreis
 2013: Stefan-Andres-Preis

Onorificenze

Altri progetti

Collegamenti esterni

Critici letterari tedeschi

redpajama_set_name: RedPajamaWikipedia


An organizational chart (org chart) is a visual aid used to clarify who reports to whom and who is responsible for what in your organization. See examples and tools that can be used to create free org charts.... The waviness of the shapes simulates a hand-drawn look by breaking up each side into sections that randomly vary off the true straight line. In the case of the circular shapes, the outline is actually a smoothed octagon with a slight randomness built into the location of each of the vertices.
Add flow charts with connectors. Before you create a flow chart, add a drawing canvas by clicking the Insert tab, clicking Shapes in the Illustrations group, and then clicking New Drawing Canvas .... Hand drawn charts are easier and more pleasant to read^, because they are familiar. Everyone had drawn and seen a large number of such charts at school. Comfort food really. Everyone had drawn and seen a large number of such charts at school.
Hand Drawn PowerPoint Templates, Presentation Slides & PPT Designs Check out our Hand Drawn PowerPoint templates and diagrams to give a handmade look to your PowerPoint presentation. If you want to give a creative touch to your PPT, then hand drawn designs are perfect for you.
How to Create a Smooth Segmented Chart using Sketch 3 App. Data presentation with Material design influences. This tutorial will teach you how to create a simple line chart, inspired by Google Material design principles using primarily the vector tool, gradients and masks in Sketch 3 app.
An organizational chart (org chart) is a visual aid used to clarify who reports to whom and who is responsible for what in your organization. See examples and tools that can be used to create free org charts.
Playing around with colours in illustration work can create distinctive results. Before starting, take time to look at areas of light and shade, and pick out certain tones to exaggerate within the piece.


Jacqui Daniels Designs is a head wrap design company based out of Florida. The focus on this build was simple and clean, while offering an eCommerce platform. We wanted to make sure the trust of the customer was earned and encompassed through the experience. By using our design techniques we were able to create a place for people from all over to want to buy from them.


Activist Bree Newsome will present the keynote address at the event. Newsome made headlines in 2015 after being arrested for tearing down a Confederate flag from a South Carolina statehouse.
Webster University's Multicultural Center and International Student Affairs (MCISA) will celebrate the life and legacy of Dr. Martin Luther King, Jr. on Monday, Jan. 30 in the Luhr Building at 5:30 p.m.
The event pays tribute to the sacrifice Dr. King, and others, made in the fight for equality, justice, and civil rights. The commemoration will also serve as a way to recognize those whose fight for the same principles have gone relatively unheralded and unnoticed.
The event will include dinner, a band, and Webster University's Gospel Choir. The keynote, entitled "Tearing Hatred from the Sky", will be delivered by activist Bree Newsome, who was arrested in 2015 after scaling the 30-foot flagpole in front of the South Carolina statehouse to remove the Confederate flag, which is seen by many as a symbol of racism and hatred.
Students, faculty, staff and community members are welcome. Free tickets can be picked up from the MCISA tables in the University Center Jan. 20-27 from 11 a.m.-1 p.m., or by registering via blogs.webster.edu/mcisa.


To Peter Turchin, who studies population dynamics at the University of Connecticut in Storrs, the appearance of three peaks of political instability at roughly 50-year intervals is not a coincidence. For the past 15 years, Turchin has been taking the mathematical techniques that once allowed him to track predator–prey cycles in forest ecosystems, and applying them to human history. He has analysed historical records on economic activity, demographic trends and outbursts of violence in the United States, and has come to the conclusion that a new wave of internal strife is already on its way. The peak should occur in about 2020, he says, and will probably be at least as high as the one in around 1970. "I hope it won't be as bad as 1870," he adds.
What I found remarkable as we have lived through the past two years (indeed, the past eight years since I made my prediction of the impending crisis), is how precisely we today are following the trajectory into crisis that my colleagues and I saw in the historical societies we have studied.
We saw all those mechanisms operating in our current crisis. Immiseration of large swaths of the American population was what fueled the successful campaign of a counter-elite presidential candidate, Donald Trump. Intra-elite conflict has reached unprecedented heights (since the First American Civil War), as the established elites are using various means at their disposal to get rid of the counter-elite chief of state. At the same time, a weird coalition of Trump and the established elites (remember, laws must be approved by the Congress) legislates deep cuts into the taxes the elites will pay, bringing the fiscal crisis of the state much sooner. Political violence has also reached new heights, although thankfully mostly demonstrators and counter-demonstrators are beaten up, not killed (a major exception was Charlottesville a year ago).
Until last year I thought that we collectively have a decent chance of avoiding the crisis, but I now have abandoned this hope. A major reason for my pessimism is the resolute refusal by our ruling class (including its both Liberal and Conservative wings) to see the real causes of the crisis. They are internal, not external. As a result, the mid-term elections will be completely free of (largely mythical) Russian influence, but no attempt is made to address the deep structural-demographic causes. All these pressures continue to increase.
Turchin says the underlying causes of violence are: 1) oversupply of labor, and 2) elite overproduction and competition. I remain skeptical of the economics behind oversupply of labor. But now in 2018 am on board with elite overproduction and competition. That's clearly tearing at the fabric of our society. I'd add that reading Turchin also reminded me of how violent the 1970s really were, which makes me less skeptical on whether violence may return. See his post on Days of Rage. In summary, I've moved my judgement of Turchin's forecasts for violence from properly rated to underrated over the past year. Turchin is not a great prose stylist, but in the end ideas are what matter. So I just bought his two most recent books on kindle. My kindle pile is pretty deep, but once I'm through I'll post something.
Bread wheat sequenced. It has 16 billion DNA letters, compared to the human genome with a paltry 3 billion.
It is hugely underrated how listening to a podcast with AirPods or headphones locates that voice in center of your head like a voice of God. Deeply intimate and possibly subconscious delivery mode.
538 has a web page predicting the outcome of the next House Congressional election.
7. Current podcast and book. My favorite podcast this week was this episode of Sinica, an interview with former China diplomat Chas Freeman. Wide ranging and interesting. My favorite book was The Enigma of Reason, which argues reason evolved as an adaptation to socially justify ourselves. Rationalizations all the way down. I'm about halfway through. So far it's rather convincing.
And that's it for this week. Thank you for reading all the way to the end!
I understand what oversupply of labor means. That was clearly a huge factor in the 1920s and 1970s crises, but like you I am skeptical about whether it is a problem today (in the UK, unemployment is at its lowest since 1975). But what on earth is elite overproduction and competition? Can you render this in concrete terms?
My take on this is too many people want the status of going to Harvard, and the plum media/tech/government jobs that go with it. So the elite college grads battle in group competition for status, rather than governing for the best interests of the nation as a whole.
I need to read Turchin's books to see if that is his view. But that is mine. When Trump says he's an Ivy League Wharton grad, and many Wharton grads hate him mentioning this, you're seeing elite zero sum competition for status.
Thanks. Harvard's website shows 39,506 candidates in search of 2,037 places for the latest year of entry. But I imagine that places for Harvard have always been highly sought-after. I find it hard to understand why this is precipitating a crisis.
Interestingly, 50.9% of admitted students were from an ethnic minority of some kind. My take is that opportunities in media, tech and banking jobs are wider than ever before, and open to a more diverse range of candidates. But I know that there is a popular perception that social mobility is in decline, the rich are getting richer, and the poor are getting poorer. Perhaps it is this perception (or mis-perception) that is the cause of unrest?


By Arezki Beloucif, he Parisian jazz vocalist who manifested his love for Japan in making the sprawling, organic and enchanting city of Tokyo his new home.
When planning an independent Japanese adventure and travelling to Tokyo alone, it's crucial to see everything you were hoping to. Whether you're taking the plunge with your first ever solo trip or are already a keen independent traveller, discover how to make the most out of your trip, uncover the best when seeking where to go in Tokyo alone and enjoy a Tokyo solo travel guide that encompasses the ideal mix of Tokyo's temples and shrines, dynamic and electric neighbourhoods, food spots and nightlife. Tokyo's traditional restaurants and charming cultural attractions provide some of the many great things to do in Tokyo alone. Navigating independently is no trouble at all as Tokyo transportation is efficient with good train links. Regardless of how you travel, make this trip for you and relish in the eclectic mixture of well-lit verandas, izakaya, green space, high-rise buildings and shrines. Whether your priority is sweet Harajuku treats, great city views or quirky neighbourhoods, you won't be stuck for what to do in Tokyo alone as you uncover its many layers. So long as you're travelling with an open mind, you will be sure to have fun.
If you find yourself wondering "how safe is Tokyo?", there's no need to worry. Tokyo solo travel is perfect as Tokyo is generally a very safe city. The Land of the Rising Sun is known for its safety and is largely brought about by the integrity standards that the Japanese observe. The locals work hard to ensure a safe, respectful environment, by taking responsibility together. You may see small children taking public transport and walking home on their own. For solo female travellers in Tokyo, it's good to know that many trains have female-only train cabins at peak and super peak times. You can walk safely and feel free but as with any major city it's never a good idea to walk alone late at night at dark in secluded places. Here's my top Tokyo solo travel tips of the best things to do in Tokyo alone.
An ideal day in Tokyo would begin for me with browsing the Nakamise shopping alley which leads to the Buddhist Asakusa Temple. Wandering past the windows, I'd browse crafts, sweets and typical Japanese souvenirs such as yukata and folding fans, perhaps buying various traditional local snacks or items which protect from harm and bad luck. Then I'd head to Sensoji or Asakusa Kannon Temple; a Buddhist temple located in Asakusa. It is one of Tokyo's most colourful and most-loved temples and legend says that in the year 628, two brothers fished a statue of Kannon, the goddess of mercy, out of the Sumida River, and even though they put the statue back into the river, it kept returning to them. So, Sensoji was built nearby for the goddess of Kannon. It's completion in 645 makes it Tokyo's oldest temple. It has an impressive atmosphere with a spiritual calm and makes a great stop off on your Tokyo solo travel itinerary.
Gadget, electronics and anime lovers will want to head to Akihabara. The so-called electric town is the centre of anime culture; home to cafes, video games shops, specialised shops selling DVDs and manga. It's very dynamic and you can check out lots of cool anime drawings of famous characters. These stores make up a huge part of the area's electric charm. Larger venues specializing in manga, anime and video games include Tokyo Anime Center. Exhibits and souvenirs are available and Radio Kaikan is worth a visit with ten floors of toys, trading cards and collectibles. Head onto side streets for smaller stores with even more specialised wares. Tiny shops hone in on microscopic niches of the electronics world. If quirky, fluorescent, over-lit stores, cosplay cafes serving tea and cakes are your thing, you won't want to miss this neighbourhood. Akihabara is one of the best things to do in Tokyo alone. It epitomises what Tokyo is all about; condensing a whole lot of something into a small space, with an added a dash of madness, weird and wonderful.
Dedicated to the deified spirits of Emperor Meiji and Empress Shoken, the Meiji Shinto Shrine is one of the best places to visit if you're seeking what to do in Tokyo alone. Close to the JR Yamanote Line's lively Harajuku Station, Meiji Shrine is adjacent to Yoyogi Park; a spacious, green, forested area and peaceful break from the dense city. The grounds and walking paths are a peaceful haven and 100,000 trees make up Meiji Jingu's tranquil forest. Visitors to the shrine can take part in traditional Shinto activities, such as making offerings at the main hall, buying charms and amulets or writing out wishes on an ema. It's well worth a visit and a must-see Tokyo for those seeking the spiritual heart of the capital.
There's plenty of shopping to do on Takeshita-dori, but all the browsing can work up an appetite. Luckily there are plenty of characteristically Harajuku sweets to be tried; from world-famous crepes to gourmet popcorn to rainbow delights and cute cake pops which are much loved by locals. In the world of Harajuku, fluffy candy floss comes in rainbows and each flavor tastes distinctly different; choose from one, three or five colours. Try Zaku Zaku which means crunchy in Japanese. The choux cream puff is an unusual shape; but has a yummy almond crust with a real crunch, and inside, a quality creamy custard from the farmlands of Hokkaido in the north.
The observatory at the top of Shinjuku is a hidden gem; despite its huge height of 209m. The observatory at the top of the skyscraper features restaurants, shops, clinics and offices and is relatively unknown to tourists. The restaurants are great places to eat if you're looking for things to do in Tokyo at night. Located on the 49th and 50th floors, the restaurants serve great food and have romantic views of Tokyo's skyline. Head up to the 50th floor observatory for picturesque views of the Shinjuku area and north-west Tokyo. On a clear day (or evening), the view of Mt. Fuji can be seen. Access is free and the Shinjuku Observatory provides a truly beautiful view of Tokyo.
My essential tips are to try to understand how the metro system transport works, as it is super useful once you know how to use it. Keep your money in pocket, as even though Tokyo is very safe, it's always good to keep money hidden. It would be wise and respectful to know a few words in Japanese. Useful phrases are arigatou gozaimasu (ありがとうございます) meaning 'thank you', onegaishimasu (お願いします), which means 'please', sumimasen (すみません) 'excuse me, hai (はい) 'yes', iie (いいえ) 'no'. And finally, nani ga oishii desu ka (お勧めは何ですか) 'what do you recommend?' The last tip: have a great trip!


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Stuart KinnerHead, Justice Health Unit, Murdoch Children's Research Institute & University of Melbourne
Professor Stuart Kinner is head of the Justice Health Unit at the University of Melbourne and Murdoch Children's Research Institute. His research focusses on the health of adolescents and adults who have contact with the criminal justice system. He Chairs Australia's National Youth Justice Health Advisory Group, Co-Chairs the Research Committee in the Academic Consortium on Criminal Justice Health, co-convenes the Justice Health Special Interest Group in the Public Health Association of Australia, serves on the Steering Committee for the Worldwide Prison Health Research & Engagement Network (WEPHREN), is a member of the WHO Steering Group on Prisons Health, and leads the Health Theme in the UN Global Study on Children Deprived of Liberty.
Michelle Telfer
Isabelle Langley

redpajama_set_name: RedPajamaCommonCrawl


We have joked that "I Come for the Treats" is our next Embody tank saying (with "Gluten/Dairy/Refined Sugar-Free" in small print on the back)! If you have been to one of my fitness classes before, you know the true highlight (forget all that muscle building, stress releasing, sweat producing, strength inducing nonsense) is the healthy treat sample given at the end!
Why do I do this? Bribery. Plain and simple. No, I am kidding! (Well, kind of, you ask women to do single arm burpees and they may never return!) Our philosophy at the studio is about lifestyle. Supporting you in a lifestyle of health and wellness. That translates well beyond our facility doors and the one hour we are blessed to spend with you a day. We want to share tools and resources that you can utilize in your everyday world to support your health and wellness. Nutrition playing such a pivotal and often challenging role. So to share a treat that is nutrient-dense, contains targeted whole food ingredients and is easy to make is a way to illustrate that you can nourish AND satisfy your cravings at the same time.
Then once a month, I put together a newsletter that contains all the recipes from the samples shared. Empowering clients to make their own treats at home!
A simple, nutrient dense way to satisfy the sweet and salty persuasions!
Place the first five ingredients in a food processor and process until the mixture is evenly ground up and sticks together nicely. Press the dough into a parchment-lined 8 by 8 inch pan. Melt the dark chocolate and coconut oil in the microwave for 60 seconds at 50% power. Stir and continue for 20 second intervals until liquid. Pour over bars and refrigerate. Top with sea salt. Cut into bars after freezing for 10 minutes.
You could also make your own chocolate topping by combining 1/4 cup coconut oil, 1/3 cup raw cacao powder and 1/4 cup raw honey and maple syrup. Melt together and spread over the bars!


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Club Maniceros de El Tigre es un equipo de fútbol venezolano, radicado en El Tigre estado Estado Anzoátegui, que militó en la Tercera División de Venezuela. Disputó sus partidos como local en el Polideportivo San Tomé, propiedad de PDVSA; actualmente tiene como su sede el Estadio Leo Morales, inaugurado a finales del año 2012

Historia

Fundado el 23 de enero de 2012, por iniciativa del TSU Rafael Ortíz director de deporte de esa ciudad y de la mano del profesor Manuel Soto, quien en alguna oportunidad llevara a la Segunda División de Venezuela a la EF Peñalver el cuadro anzoatiguense comenzó su participación en los torneos profesionales de FVF en la Tercera División Venezolana 2012, torneo disputado en la segunda mitad de la temporada 2011-2012, que fue llamado Torneo de Nivelación 2012. En el mencionado torneo tuvo rivales como Margarita FC, Libertad Socialista FC y el hoy desaparecido Unión Atlético Piar; tras 10 jornadas disputadas, los guerreros del sur lograron culminar en la segunda posición del Grupo Oriental, sumando un total de 17 puntos, logrando así los méritos deportivos para poder disputar la siguiente temporada en la tercera categoría del balompié venezolano.

Tras el semestre de debut, toma parte en la Tercera División Venezolana 2012/13, que comenzó con el Torneo Clasificatorio 2012, en el Grupo Oriental II, teniendo como rivales a Fundación Cesarger FC, Margarita FC y la filial del Deportivo Anzoátegui, Deportivo Anzoátegui B. Muy distinta fue la historia para el cuadro tigrense en relación con el semestre anterior: solo un empate y 9 derrotas a lo largo del semestre, le situaron en la última casilla de grupo. el 14 de octubre de 2012 enfrentó a Estudiantes de Caroní FC, en lo que fue el primer partido del cuadro estudiantil tras la remodelación del Estadio Polideportivo El Gallo, terminando el marcador 3 goles por 1 a favor del cuadro local.

Tras su participación en la primera mitad de la temporada 2012-2013 de la Tercera División, el cuadro anzoatiguense no ha vuelto a tomar parte en los torneos profesionales de la FVF, se ha mantenido compitiendo a nivel local y regional, siendo una de las instituciones del país que cuenta con todas las categorías, incluyendo el fútbol femenino.
En el fútbol menor Fundación Maniceros de El Tigre obtuvo durante el año 2015 grandes logros que le permitieron titularse campeones en las categorías Sub06, Sub08, Sub10 y Sub12 lo que conllevó a que fuesen designados como Cuerpo Técnico de las selecciones que viajaron a Maracay (Aragua) y Cabudare (Lara) donde se alcanzaron los cuartos de final ubicándonos dentro de las 16 mejores escuelas del país.
Durante este año 20 jugadores de nuestra fundación han formado parte de las selecciones Sub07 (2009-2010), Sub08 (2008), Sub09 (2007), Sub10 (2006) y Sub12 (2004) del estado Anzoátegui que nos ha representado en los distintos nacionales organizados por la Liga Nacional de Futbol Menor donde han tenido destacadas actuaciones, resaltando entre ellos Hernán Salazar (Sub07), Andrés Brito Malaspina (2008), Pedro Rodríguez (2008), Carlos A. Wong (2008), Carlos Cagua (2004), Carlos M. Wong (2004) y Marcos Bucan (2004) quienes recibieron el llamado a formar parte de la Selección Nacional Tricolor de sus categorías.
En la actualidad Andrés Brito España ejerce la presidencia del club con un plan de trabajo enmarcado dentro del crecimiento del futbol menor así como el retorno de Maniceros de El Tigre a la elite del balompié, para esto Brito España se ha hecho rodear de un grupo destacado de personas para impulsar las metas trazadas a corto y mediano plazo.

Referencias

El Tigre (Anzoátegui)
Equipos de fútbol de Venezuela


I love a good theme, it helps me write. I like delving into a topic and exploring my thoughts about it. I've really been enjoying the prompts put out as part of Slow Fashion October. The theme of this week is Loved. I had actually thought about sharing some of these garments a few months ago and had done some writing but never got around to publishing. I'm happy to have the perfect reason to do so!
Today I'm sharing some of my favorite 'well loved' garments, some of which I've had for quite a long time. Some of these are things I've made myself, some I've picked up in my travels. I don't necessarily wear all of them, and some I don't even own anymore (just have pictures) but I think they all tell nice stories.
This skirt was one of the more ambitious things I made early on in my sewing life, I believe during my first year of college. I can't recall where the fabric came from and I know I did not use a pattern. I looked at a RTW denim skirt that I loved and mentally deconstructed it. To this day, I'm rather impressed that I was able to grasp the concept of a fly zip and slash pockets. The button came from a collection gifted to me by a family friend who lived in Arizona. The back slit shows numerous repairs. This short skirt was worn at the most bicycling period of my life and had a tendency to rip at the seam.
The gusset, if you can call it that, was added at a later repair stage. This is a skirt I'd often thought about remaking. I did end up creating a very similar denim skirt using the Closet Case Files Ginger Jeans pattern and wrote a tutorial about how to do it here!
This pair of cowboy boots belonged to my mom. She gave them to me in high school. At that point in time, these were basically the most incredibly pair of shoes I had ever owned. Simple, not elaborate like most cowboy boots you see. They fit perfectly with my quirky, transitioning out of punk rock art school persona. When I moved to Boston for college, these were the only shoes I came with. When it started to get cold, snow and rain would leak through the growing holes in the bottom of the boots. I would cut out layers of cardboard and use them as insoles to keep my feet warm and dry. Eventually, my lovely aunt bought me a new pair of boots for winter and these were retired. I no longer own them, as they were too damaged to repair. I think they are one of the most punk rock items I have ever worn. Of course, the shirt following ranks pretty high too.
This t shirt was bought brand new from a family friend's store on Fire Island, NY. I believe I was 10. I wore it periodically in typical tshirt fashion and for some reason, it stayed in my drawer. I was not much of a logo tshirt wearer beyond the age of 12 (opting for more 'alternative' style) and at that point the shirt was relegated to the 'sleepwear' department. If you've ever wanted a 'distressed' shirt, or drooled over a parent or ex partner's beloved and bedraggled rock tee, I'll share the secret to fast-tracking a vintage look: Sleep in the shirt as much as possible. I've watched the crispiest of tees with the thickest of screen printing be reduced to gossamer threads this way. My Fire Island shirt is no exception.
At some point, small pinholes started to develop. A large splash during a fateful laundering turned the solid blue jersey into a sort of cloudscape. It's actually remarkable how it looks so much like a cloud print by complete accident. I don't think I could recreate it if I tried.
After a tremendous amount of sleep wear, I began to reconsider the shirt as I reached the pinnacle of my 'punkdom' as a teen. Suddenly, my touristy summer tshirt (with the help of some rogue bleach I might add) became the ultimate punk rock garment. I continued to wear this one until both my punk phase, and the shirt itself, ran its natural course and reached its ultimate un-wearability.
These were my mom's shoes. My mom gives me a lot of her shoes because we are the same size foot (my grandma has the same size too, and they both have fantastic taste, so I gladly took their hand me downs). My mom wore them from my age until her forties. These are the kind of shoes you could refer to as timeless. She bought two pairs, one gold and one black. The gold pair were at some point destined to be black as well, but only one received the dye. So now I have two pair, three black, one gold. The idea that well made shoes last a lifetime is true, evidenced by the duration of these flats. I can even wear them without socks and get away with it.
When I moved to Boston for college from southern California, I was very ill equipped for the cold weather. I discovered the Garment District (and their "Dollar A Pound" clothing section) a few months into the fall and it became a frequent haunt of mine and the source of about 75% of my college wardrobe. I remember picking up quite a few wool sweaters, an entirely new concept to me, including this lovely brown cardigan. The pockets are fake. The buttons were systematically replaced as they fell off while traversing the streets of Boston. I found this brown cardigan to be exactly the right softness, length, color, collar, and warmth.
Large holes were mended with colorful darning, using crewel embroidery thread from kits I often picked up at thrift stores. The "Utopia" pin came from my partner's former radio show (there were 12 pins overall I believe) and once it went on the sweater it never came off. This mostly lives in the closet collecting cat hair as I can't bear to part with it, but it's a bit too ratty for wearing out into the world.
When I went to visit my partner's family in northern California for the first time, we made a trip to some good friends of theirs' dairy farm. We spent the day eating delicious lunch, driving around the property looking at cows, and watching bald eagles by the river bank. It was a lovely outing. At this time in my life, I was quite fond of wearing vintage clothing and my job at a vintage clothing boutique was part of the elevator pitch my in-laws had been giving other friends and family. At the end of our visit, the one of the family friends who had grown up on that farm led me to a closet and revealed a small collection of vintage clothing that had belonged to his mother. A few suits, a bed jacket, a coat, and two handknit sweaters just my size, somewhat moth-eaten but beautiful.
While the suits don't fit - they live as display pieces in my studio - the sweaters were washed, darned, and put into heavy rotation. This one is my favorite. The navy flannel elbow patches were added to worn elbows. The buttons are original. My cat loves sleeping on this one too.
While these garments (with exception of the shoes) don't get much wear anymore, I can't bear to part with them. I thought sharing about them would serve to memorialize them, regardless of where they end up (though, most likely, I'll keep them).
Do you have any beloved garments you no longer wear but hang on to? What is the story behind them?


text:
Category: economic damages & lost profits
The Business Valuation Update (BVU), a monthly newsletter with searchable online access, includes new thinking from leading professionals, detailed reports from valuation conferences, analysis of new business valuation approaches, thorough analysis of "landmark" legal cases in key business valuation issues, regulatory and standards updates, and much more. Learn more >>
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Business Valuation Update Yearbook, 2017 Edition
BVR has you covered with the Business Valuation Update Yearbook 2017. This newest edition from the publishers of Business Valuation Update covers the year's most groundbreaking and thought-provoking advancements in business valuation including IRC Sec. 2704, DLOM, cost of capital, and more. This critical desktop reference keeps you ahead of your peers with on-the-ground reporting from valuation experts, thought-leaders, and BVR's editorial team. Learn more >>
BVR has you covered with the Business Valuation Update Yearbook 2018. This newest edition from the publishers of Business Valuation Update covers the year's most groundbreaking and thought-provoking advancements in business valuation, and more. This critical desktop reference keeps you ahead of your peers with on-the-ground reporting from valuation experts, thought-leaders, and BVR's editorial team. Learn more >>
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Always a highly-anticipated annual publication, the Business Valuation Update Yearbook 2021 covers the year's most groundbreaking and thought-provoking advancements on valuation methodologies in the face of a global pandemic. It also captures, changes in regulations and professional standards, key takeaways from the best virtual conferences, and tactical practice-building ideas. This critical desktop reference puts you ahead of the competition with on-the-ground reporting from valuation experts, thought-leaders, and BVR's expert editorial and legal teams. Learn more >>
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text:
Dave Evans (August 31, 1898 – March 31, 1974) was an American racing driver.

Evans was born in Los Angeles, California. In 1931, he performed a remarkable feat when his Cummins Diesel Special completed the entire Indy 500 without a pit stop. He died in  Dell, Montana, aged 75.

Indy 500 results

Notes

1898 births
1974 deaths
Indianapolis 500 drivers
Racing drivers from Los Angeles


One month in and the 90's children's craze Pokémon has been more than resurrected. The augmented reality gaming app Pokémon Go has smashed all sorts of records, including an estimated 75 million downloads and $200 million in revenue so far. And this geocaching application is no child's play. It exceeds Twitter in active users; 40% of these being 25 years of age or older. Having achieved the kind of impact and audiences that most brands only dream of, what can marketers learn from the frenzy?
You don't always have to start again or invent something new. You can update and refresh. Creators Niantic took a game first seen in 1996, and now covers video games, trading card games, animated television shows and movies, comic books, and toys and it gave new life. As a franchise that has been around for 20 years, Pokémon has developed strong connections with its fans evoking nostalgia in some and novelty for others. Having an established community available, and the ability to provide something fresh means that the brand's growth is somewhat organic, evolving, and as a result, very powerful.
Easy to use, the game is accessible to anyone with a smartphone. Through a device that lives in hands and pockets of the majority of the population exists an amazing opportunity to connect. An always-on conversation allows people to participate whenever and wherever they choose to, taking control of their interaction. Despite this, it's also disruptive. Even those not playing the game are interested, asking for an explanation and becoming more aware. Via GPS technology, players are encouraged to visit new locations, and this virtual overlay is bringing people to businesses that they may not have visited otherwise. Wholefoods successfully used geofencing in the US to not only attract consumers to their own stores with offers and incentives, but woo them away from competitors.
In the age of social, it seems almost peripheral to mention the importance of communicating regularly with your brand fan base. However, Niantic, the developer of Pokémon Go have done the most basic of social marketing errors. When the Pokémon Go tracker feature 'broke' very soon after the game was released, fans waited (patiently) for it to be fixed. A few intrepid coders took on the challenge of devising solutions to the problem, which led to the rise of services like PokéVision. Yet, in the first major update to the game since it launched nearly one month ago, Niantic didn't fix the glitch. Instead, they removed the tracking system altogether and sent cease-and-desist letters to services such as PokéVision. Their fans are mad; at both the tech updates and the lack of communication.
There are very few physical objects that we need in the modern world. The most successful brands do not necessarily have business models based on selling products, but instead, focus their attention on creating experiences for consumers. Think of Secret Cinema. It's turned watching an old film into a lucrative business that attracts thousands of attendees to their captivating events. The Pokémon Go app has multiple benefits – it's a game, it's immersive, gets people moving, offers social opportunities, challenges individuals and encourages exploration of communities. People feel as though they are part of something and influencing the trajectory of a brand interaction, lending the experience meaning. Successful brands are those that are culturally immersed and in tune with their consumers and their consumers' lives.
Pikachu and his pals definitely have some things to teach us. Using innovative technology that is engaging, offers adventure in an accessible way, resonates with people in their own lives, offers a new lens on something familiar, and is disruptive without throwing things into disarray is how marketers and brands can Power Up, be Super Effective, win Prestige and Achieve.


text:
الموسوعة الدوائية
Albumin-bound Paclitaxel for Injectable Suspension (Abraxane)
حدث بتاريخ: 30 تشرين2/نوفمبر 2017
The most common adverse reactions ( ≥ 20%) with single-agent use of ABRAXANE in metastatic breast cancer are alopecia, neutropenia, sensory neuropathy, abnormal ECG, fatigue/asthenia, myalgia/arthralgia, AST elevation, alkaline phosphatase elevation, anemia, nausea, infections, and diarrhea.
The most common adverse reactions ( ≥ 20%) of ABRAXANE in combination with carboplatin for non-small cell lung cancer are anemia, neutropenia, thrombocytopenia, alopecia, peripheral neuropathy, nausea, and fatigue. The most common serious adverse reactions of ABRAXANE in combination with carboplatin for non-small cell lung cancer are anemia (4%) and pneumonia (3%). The most common adverse reactions resulting in permanent discontinuation of ABRAXANE are neutropenia (3%), thrombocytopenia (3%), and peripheral neuropathy (1%). The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (24%), thrombocytopenia (13%), and anemia (6%). The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (41%), thrombocytopenia (30%), and anemia (16%).
In a randomized open-label trial of ABRAXANE in combination with gemcitabine for pancreatic adenocarcinoma [see Clinical Studies], the most common ( ≥ 20%) selected (with a ≥ 5% higher incidence) adverse reactions of ABRAXANE are neutropenia, fatigue, peripheral neuropathy, nausea, alopecia, peripheral edema, diarrhea, pyrexia, vomiting, decreased appetite, rash, and dehydration. The most common serious adverse reactions of ABRAXANE (with a ≥ 1% higher incidence) are pyrexia (6%), dehydration (5%), pneumonia (4%) and vomiting (4%). The most common adverse reactions resulting in permanent discontinuation of ABRAXANE are peripheral neuropathy (8%), fatigue (4%) and thrombocytopenia (2%). The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (10%) and peripheral neuropathy (6%). The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (16%), thrombocytopenia (12%), fatigue (8%), peripheral neuropathy (15%), anemia (5%) and diarrhea (5%).
Clinical Trials Experience in Metastatic Breast Cancer
Table 6 shows the frequency of important adverse events in the randomized comparative trial for the patients who received either single-agent ABRAXANE or paclitaxel injection for the treatment of metastatic breast cancer.
Table 6: Frequencya of Important Treatment Emergent Adverse Events in the Randomized Metastatic Breast Cancer Study on an Every-3-Weeks Schedule
Percent of Patients
ABRAXANE 260 mg/m² over 30 min
(n=229) Paclitaxel Injection 175 mg/m² over 3 hb
< 2.0 x 109/L 80 82
< 0.5 x 109/L 9 22
< 100 x 109/L 2 3
< 50 x 109/L < 1 < 1
< 11 g/dL 33 25
< 8 g/dL 1 < 1
Infections 24 20
Febrile Neutropenia 2 1
Neutropenic Sepsis < 1 < 1
Bleeding 2 2
Hypersensitivity Reactionc
All 4 12
Severed 0 2
Vital Sign Changes During Administration
Bradycardia < 1 < 1
Hypotension 5 5
Severe Cardiovascular Eventsd 3 4
All Patients 60 52
Patients with Normal Baseline 35 30
Dyspnea 12 9
Any Symptoms 71 56
Severe Symptomsd 10 2
Myalgia / Arthralgia
Severe Symptomsd 8 4
Fluid Retention/Edema
Any Symptoms 10 8
Severe Symptomsd 0 < 1
Severe Symptomsd < 1 1
Mucositis
Any Symptoms 7 6
Alopecia 90 94
Hepatic (Patients with Normal Baseline)
Bilirubin Elevations 7 7
Alkaline Phosphatase Elevations 36 31
AST (SGOT) Elevations 39 32
Injection Site Reaction < 1 1
aBased on worst grade by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.
bPaclitaxel injection patients received premedication.
cIncludes treatment-related events related to hypersensitivity (e.g., flushing, dyspnea, chest pain, hypotension) that began on a day of dosing.
dSevere events are defined as at least grade 3 toxicity.
Adverse Event Experiences by Body System
Hematologic Disorders
Neutropenia was dose dependent and reversible. Among patients with metastatic breast cancer in the randomized trial, neutrophil counts declined below 500 cells/mm³ (Grade 4) in 9% of the patients treated with a dose of 260 mg/m² compared to 22% in patients receiving paclitaxel injection at a dose of 175 mg/m² . Pancytopenia has been observed in clinical trials.
Infectious episodes were reported in 24% of the patients treated with ABRAXANE. Oral candidiasis, respiratory tract infections and pneumonia were the most frequently reported infectious complications.
Hypersensitivity Reactions (HSRs)
Grade 1 or 2 HSRs occurred on the day of ABRAXANE administration and consisted of dyspnea (1%) and flushing, hypotension, chest pain, and arrhythmia (all < 1%). The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied.
Hypotension, during the 30-minute infusion, occurred in 5% of patients. Bradycardia, during the 30-minute infusion, occurred in < 1% of patients. These vital sign changes most often caused no symptoms and required neither specific therapy nor treatment discontinuation.
Severe cardiovascular events possibly related to single-agent ABRAXANE occurred in approximately 3% of patients. These events included cardiac ischemia/infarction, chest pain, cardiac arrest, supraventricular tachycardia, edema, thrombosis, pulmonary thromboembolism, pulmonary emboli, and hypertension. Cases of cerebrovascular attacks (strokes) and transient ischemic attacks have been reported.
Electrocardiogram (ECG) abnormalities were common among patients at baseline. ECG abnormalities on study did not usually result in symptoms, were not dose-limiting, and required no intervention. ECG abnormalities were noted in 60% of patients. Among patients with a normal ECG prior to study entry, 35% of all patients developed an abnormal tracing while on study. The most frequently reported ECG modifications were non-specific repolarization abnormalities, sinus bradycardia, and sinus tachycardia.
Dyspnea (12%), cough (7%), and pneumothorax ( < 1%) were reported after treatment with ABRAXANE.
The frequency and severity of sensory neuropathy increased with cumulative dose. Sensory neuropathy was the cause of ABRAXANE discontinuation in 7/229 (3%) patients. Twenty-four patients (10%) treated with ABRAXANE developed Grade 3 peripheral neuropathy; of these patients, 14 had documented improvement after a median of 22 days; 10 patients resumed treatment at a reduced dose of ABRAXANE and 2 discontinued due to peripheral neuropathy. Of the 10 patients without documented improvement, 4 discontinued the study due to peripheral neuropathy.
No Grade 4 sensory neuropathies were reported. Only one incident of motor neuropathy (Grade 2) was observed in either arm of the controlled trial.
Ocular/visual disturbances occurred in 13% of all patients (n=366) treated with ABRAXANE and 1% were severe. The severe cases (keratitis and blurred vision) were reported in patients who received higher doses than those recommended (300 or 375 mg/m²). These effects generally have been reversible.
Arthralgia/Myalgia
The symptoms were usually transient, occurred two or three days after ABRAXANE administration, and resolved within a few days.
Grade 3 or 4 elevations in GGT were reported for 14% of patients treated with ABRAXANE and 10% of patients treated with paclitaxel injection in the randomized trial.
Overall 11% of patients experienced creatinine elevation, 1% severe. No discontinuations, dose reductions, or dose delays were caused by renal toxicities.
Other Clinical Events
Nail changes (changes in pigmentation or discoloration of nail bed) have been reported. Edema occurred in 10% of patients; no patients had severe edema. Dehydration and pyrexia were also reported.
Clinical Trials Experience in Non-Small Cell Lung Cancer
Adverse reactions were assessed in 514 ABRAXANE/carboplatin-treated patients and 524 paclitaxel injection/carboplatin-treated patients receiving first-line systemic treatment for locally advanced (stage IIIB) or metastatic (IV) non-small cell lung cancer (NSCLC) in a multicenter, randomized, open-label trial. ABRAXANE was administered as an intravenous infusion over 30 minutes at a dose of 100 mg/m² on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel injection was administered as an intravenous infusion over 3 hours at a dose of 200 mg/m², following premedication. In both treatment arms carboplatin at a dose of AUC = 6 mg•min/mL was administered intravenously on Day 1 of each 21-day cycle after completion of ABRAXANE/paclitaxel infusion. The differences in paclitaxel dose and schedule between the two arms limit direct comparison of dose- and schedule-dependent adverse reactions. Among patients evaluable for adverse reactions, the median age was 60 years, 75% were men, 81% were White, 49% had adenocarcinoma, 43% had squamous cell lung cancer, 76% were ECOG PS 1. Patients in both treatment arms received a median of 6 cycles of treatment.
The following common ( ≥ 10% incidence) adverse reactions were observed at a similar incidence in ABRAXANE plus carboplatintreated and paclitaxel injection plus carboplatin-treated patients: alopecia 56%, nausea 27%, fatigue 25%, decreased appetite 17%, asthenia 16%, constipation 16%, diarrhea 15%, vomiting 12%, dyspnea 12%, and rash 10% (incidence rates are for the ABRAXANE plus carboplatin treatment group).
Table 7 provides the frequency and severity laboratory-detected abnormalities which occurred with a difference of ≥ 5% for all grades (1-4) or ≥ 2% for Grade 3-4 toxicity between ABRAXANE plus carboplatin-treated patients or paclitaxel injection plus carboplatin-treated patients.
Table 7: Selected Hematologic Laboratory-Detected Abnormalities With a Difference of ≥ 5% for grades (1-4) or ≥ 2% for Grade 3-4 Toxicity Between Treatment Groups
ABRAXANE (100 mg/m² weekly) plus carboplatin Paclitaxel Injection (200 mg/m² every 3 weeks) plus carboplatin
(%) Grade 3-4
(%) Grades 1-4
Anemia1,2 98 28 91 7
Neutropenia1,3 85 47 83 58
Thrombocytopenia1,3 68 18 55 9
1508 patients assessed in ABRAXANE/carboplatin-treated group
2514 patients assessed in paclitaxel injection/carboplatin-treated group
Table 8 provides the frequency and severity of adverse reactions, which occurred with a difference of ≥ 5% for all grades (1-4) or ≥ 2% for Grade 3-4 between either treatment group for the 514 ABRAXANE plus carboplatin-treated patients compared with the 524 patients who received paclitaxel injection plus carboplatin.
Table 8: Selected Adverse Reactions with a Difference of ≥ 5% for All Grade Toxicity or ≥ 2% for Grade 3-4 Toxicity Between Treatment Groups
System Organ Class MedDRA v 12.1 Preferred Term ABRAXANE (100 mg/m² weekly) + carboplatin (N=514) Paclitaxel Injection (200 mg/m² every 3 weeks) + carboplatin (N=524)
Grade 1-4 Toxicity
(%) Grade 3-4 Toxicity
(%) Grades 1-4 Toxicity
Nervous system disorders Peripheral neuropathya 48 3 64 12
General disorders and administration site conditions Edema peripheral 10 0 4 < 1
Respiratory thoracic and mediastinal disorders Epistaxis 7 0 2 0
Musculoskeletal and connective Arthralgia 13 < 1 25 2
tissue disorders Myalgia 10 < 1 19 2
aPeripheral neuropathy is defined by the MedDRA Version 14.0 SMQ neuropathy (broad scope).
For the ABRAXANE plus carboplatin treated group, 17/514 (3%) patients developed Grade 3 peripheral neuropathy and no patients developed Grade 4 peripheral neuropathy. Grade 3 neuropathy improved to Grade 1 or resolved in 10/17 patients (59%) following interruption or discontinuation of ABRAXANE.
Clinical Trials Experience in Adenocarcinoma of the Pancreas
Adverse reactions were assessed in 421 patients who received ABRAXANE plus gemcitabine and 402 patients who received gemcitabine for the first-line systemic treatment of metastatic adenocarcinoma of the pancreas in a multicenter, multinational, randomized, controlled, open-label trial. Patients received a median treatment duration of 3.9 months in the ABRAXANE/gemcitabine group and 2.8 months in the gemcitabine group. For the treated population, the median relative dose intensity for gemcitabine was 75% in the ABRAXANE/gemcitabine group and 85% in the gemcitabine group. The median relative dose intensity of ABRAXANE was 81%.
Table 9 provides the frequency and severity of laboratory-detected abnormalities which occurred at a higher incidence for Grades 14 ( ≥ 5%) or for Grade 3-4 ( ≥ 2%) toxicity in ABRAXANE plus gemcitabine-treated patients.
Table 9: Selected Hematologic Laboratory-Detected Abnormalities with a Higher Incidence ( ≥ 5% for Grades 1-4 or ≥ 2% for Grades 3-4 Events) in the ABRAXANE/Gemcitabine Arm
ABRAXANE(125 mg/m²)/ Gemcitabined Gemcitabine
Neutropeniaa,b 73 38 58 27
Thrombocytopeniab,c 74 13 70 9
a405 patients assessed in ABRAXANE/gemcitabine-treated group
b388 patients assessed in gemcitabine-treated group
c404 patients assessed in ABRAXANE/gemcitabine-treated group
dNeutrophil growth factors were administered to 26% of patients in the ABRAXANE/gemcitabine group.
Table 10 provides the frequency and severity of adverse reactions which occurred with a difference of ≥ 5% for all grades or ≥ 2% for Grade 3 or higher in the ABRAXANE plus gemcitabine-treated group compared to the gemcitabine group.
Table 10: Selected Adverse Reactions with a Higher Incidence ( ≥ 5% for All Grade Toxicity or ≥ 2% for Grade 3 or Higher Toxicity) in the ABRAXANE/Gemcitabine Arm
System Organ Class Adverse Reaction ABRAXANE (125 mg/m²) and gemcitabine
(N=421) Gemcitabine
All Grades Grade 3 or Higher All Grades Grade 3 or Higher
General disorders and administration site conditions Fatigue 248 (59%) 77 (18%) 183 (46%) 37 (9%)
Peripheral edema 194 (46%) 13 (3%) 122 (30%) 12 (3%)
Pyrexia 171 (41%) 12 (3%) 114 (28%) 4 (1%)
Asthenia 79 (19%) 29 (7%) 54 (13%) 17 (4%)
Mucositis 42 (10%) 6 (1%) 16 (4%) 1 ( < 1%)
Gastrointestinal disorders Nausea 228 (54%) 27 (6%) 192 (48%) 14 (3%)
Diarrhea 184 (44%) 26 (6%) 95 (24%) 6 (1%)
Vomiting 151 (36%) 25 (6%) 113 (28%) 15 (4%)
Skin and subcutaneous tissue disorders Alopecia 212 (50%) 6 (1%) 21 (5%) 0
Rash 128 (30%) 8 (2%) 45 (11%) 2 ( < 1%)
Nervous system disorders Peripheral neuropathya 227 (54%) 70 (17%) 51 (13%) 3 (1%)
Dysgeusia 68 (16%) 0 33 (8%) 0
Headache 60 (14%) 1 ( < 1%) 38 (9%) 1 ( < 1%)
Metabolism and nutrition disorders Decreased appetite 152 (36%) 23 (5%) 104 (26%) 8 (2%)
Dehydration 87 (21%) 31 (7%) 45 (11%) 10 (2%)
Hypokalemia 52 (12%) 18 (4%) 28 (7%) 6 (1%)
Respiratory, thoracic and mediastinal disorders Cough 72 (17%) 0 30 (7%) 0
Epistaxis 64 (15%) 1 ( < 1%) 14 (3%) 1 ( < 1%)
Infections and infestations Urinary tract infections b 47 (11%) 10 (2%) 20 (5%) 1 ( < 1%)
Musculoskeletal and connective tissue disorders Pain in extremity 48 (11%) 3 (1%) 24 (6%) 3 (1%)
Arthralgia 47 (11%) 3 (1%) 13 (3%) 1 ( < 1%)
Myalgia 44 (10%) 4 (1%) 15 (4%) 0
Psychiatric disorders Depression 51 (12%) 1 ( < 1%) 24 (6%) 0
aPeripheral neuropathy is defined by the MedDRA Version 15.0 Standard MedDRA Query neuropathy (broad scope).
bUrinary tract infections includes the preferred terms of: urinary tract infection, cystitis, urosepsis, urinary tract infection bacterial, and urinary tract infection enterococccal.
Additional clinically relevant adverse reactions that were reported in < 10% of the patients with adenocarcinoma of the pancreas who received ABRAXANE/gemcitabine included:
Infections & infestations: oral candidiasis, pneumonia
Vascular disorders: hypertension
Cardiac disorders: tachycardia, congestive cardiac failure
Eye disorders: cystoid macular edema
Grade 3 peripheral neuropathy occurred in 17% of patients who received ABRAXANE/gemcitibine compared to 1% of patients who received gemcitabine only; no patients developed grade 4 peripheral neuropathy. The median time to first occurrence of Grade 3 peripheral neuropathy in the ABRAXANE arm was 140 days. Upon suspension of ABRAXANE dosing, the median time to improvement from Grade 3 peripheral neuropathy to ≤ Grade 1 was 29 days. Of ABRAXANE-treated patients with Grade 3 peripheral neuropathy, 44% resumed ABRAXANE at a reduced dose.
Sepsis occurred in 5% of patients who received ABRAXANE/gemcitabine compared to 2% of patients who received gemcitabine alone. Sepsis occurred both in patients with and without neutropenia. Risk factors for sepsis included biliary obstruction or presence of biliary stent.
Pneumonitis
Pneumonitis occurred in 4% of patients who received ABRAXANE/gemcitabine compared to 1% of patients who received gemcitabine alone. Two of 17 patients in the ABRAXANE arm with pneumonitis died.
Post-Marketing Experience with ABRAXANE and other Paclitaxel Formulations
Unless otherwise noted, the following discussion refers to the adverse reactions that have been identified during post-approval use of ABRAXANE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. In some instances, severe events observed with paclitaxel injection may be expected to occur with ABRAXANE.
Severe and sometimes fatal hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied.
There have been reports of congestive heart failure and left ventricular dysfunction with ABRAXANE. Most of the individuals were previously exposed to cardiotoxic drugs, such as anthracyclines, or had underlying cardiac history.
There have been reports of pneumonitis, interstitial pneumonia and pulmonary embolism in patients receiving ABRAXANE and reports of radiation pneumonitis in patients receiving concurrent radiotherapy. Reports of lung fibrosis have been received as part of the continuing surveillance of paclitaxel injection safety and may also be observed with ABRAXANE.
Cranial nerve palsies and vocal cord paresis have been reported, as well as autonomic neuropathy resulting in paralytic ileus.
Reports in the literature of abnormal visual evoked potentials in patients treated with paclitaxel injection suggest persistent optic nerve damage. These may also be observed with ABRAXANE.
Reduced visual acuity due to cystoid macular edema (CME) has been reported during treatment with ABRAXANE as well as with other taxanes. After cessation of treatment, CME improves and visual acuity may return to baseline.
Reports of hepatic necrosis and hepatic encephalopathy leading to death have been received as part of the continuing surveillance of paclitaxel injection safety and may occur following ABRAXANE treatment.
Gastrointestinal (GI)
There have been reports of intestinal obstruction, intestinal perforation, pancreatitis, and ischemic colitis following ABRAXANE treatment. There have been reports of neutropenic enterocolitis (typhlitis), despite the coadministration of G-CSF, occurring in patients treated with paclitaxel injection alone and in combination with other chemotherapeutic agents.
Injection Site Reaction
There have been reports of extravasation of ABRAXANE. Given the possibility of extravasation, it is advisable to monitor closely the ABRAXANE infusion site for possible infiltration during drug administration.
Severe events such as phlebitis, cellulitis, induration, necrosis, and fibrosis have been reported as part of the continuing surveillance of paclitaxel injection safety. In some cases the onset of the injection site reaction in paclitaxel injection patients either occurred during a prolonged infusion or was delayed by a week to ten days. Recurrence of skin reactions at a site of previous extravasation following administration of paclitaxel injection at a different site, i.e., "recall", has been reported.
Skin reactions including generalized or maculopapular rash, erythema, and pruritus have been observed with ABRAXANE. There have been case reports of photosensitivity reactions, radiation recall phenomenon, and in some patients previously exposed to capecitabine, reports of palmar-plantar erythrodysesthesia. Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported.
There have been reports of conjunctivitis, cellulitis, and increased lacrimation with paclitaxel injection.
Accidental Exposure
No reports of accidental exposure to ABRAXANE have been received. However, upon inhalation of paclitaxel, dyspnea, chest pain, burning eyes, sore throat, and nausea have been reported. Following topical exposure, events have included tingling, burning, and redness.
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