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Summary for 1104 17th AVE / Parcel ID 1337800315 / Inv #
Historic Name: Roy, C. L., Residence Common Name:
Style: Arts & Crafts Neighborhood: Capitol Hill
This house, in the English Arts & Carfts style, was designed by architect Frederick Sexton for C. L. Roy, owner of a lumber mill; it is said that he asked Sexton to model this house on a Roy family ancestral home in England. Sexton was born and educated in England and practiced in Tacoma and Everett before coming to Seattle in 1901. He designed many commercial and public buildings including schools and libraries, as well as a number of houses including the nearby Parker-Fersen House, a city landmark. This block is within the original Capitol Hill of James A. Moore, who gave the area its name. In 1900 Moore, who had already developed other Seattle neighborhoods, purchased and began platting 160 acres, roughly between 11th and 20th avenues, from Roy Street north to Galer. Before selling lots for construction, he graded and paved the streets (eliminating the dust that plagued many sections), installed sidewalks, water mains and sewer lines, and planned for street lights and telephone poles. Lots went on sale in 1901, heavily promoted to attract local business leaders as residents. The response was immediate. The quality infrastructure, convenient transportation, schools and other amenities proved to be very popular and the area was largely developed, with sizable, attractive houses, within only a few years.
This house has a cross-gable form, with a wide front gable. The first floor is clad with brick, with stucco and half timbering above. An unusually wide decorative wood band separates the materials. The gabled entry, at the northwest corner, is at-grade, and has relatively small timbers, more typical of the English Arts and Crafts style than the heavier, more solid Tudor timbers. The south end has a second-story porch with a brick balustrade. The north end has a gabled porte chochere. Most windows are simple one-over-one sash, with some casements. Some appear to be replacements.
Detail for 1104 17th AVE / Parcel ID 1337800315 / Inv #
Cladding(s): Brick, Stucco Foundation(s): Concrete - Poured
Changes to Windows: Slight
City of Seattle, Department of Planning and Development, Microfilm Records.
Photo collection for 1104 17th AVE / Parcel ID 1337800315 / Inv #


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Q: I started working in ocaml and i can't figure out a small thing about nat types I am trying to write a function of type nat -> nat -> nat -> nat
which i named sudan_nat it works on the principle of sudan function
**
Wikipedia:
   https://en.wikipedia.org/wiki/Sudan_function

//This is the type definition
type nat = Zero | Succ of nat

let add_nat m n =
  let rec helper m = match m with Zero -> n | Succ m -> Succ (helper m)
  in helper m

let zero_nat = Zero
let one_nat  = Succ zero_nat
let two_nat  = Succ one_nat
let four_nat  = add_nat two_nat two_nat`

let sudan_nat m n p =
  let rec helper m n = match m with Zero -> n | Succ m -> Succ (helper m n)
  in helper (add_nat (add_nat m n) p) one_nat

This is the code i wrote for the sudan_nat
My case for testing output is
((sudan_nat one_nat two_nat two_nat) = (add_nat (add_nat four_nat four_nat) four_nat))
Succ (Succ (Succ (Succ (Succ (Succ Zero)))))

This is the result for left side
Succ
 (Succ
   (Succ (Succ (Succ (Succ (Succ (Succ (Succ (Succ (Succ (Succ Zero)))))))))))

This is the result of right side i have been scratching my head for hours now any kind of suggestion is welcomed thank you

A: four_nat is Succ (Succ (Succ (Succ Zero))). That's 4 Succ constructors. You've added 3 of these together, so you have... 12. 4 times 3 = 12.
When it comes to evaluating sudan_nat nat_one nat_two nat_two it breaks down:
sudan_nat nat_one nat_two nat_two
helper (add_nat (add_nat nat_one nat_two) nat_two) one_nat
helper (add_nat (add_nat Zero nat_two) nat_two) one_nat
helper (add_nat nat_two nat_two) one_nat
helper nat_four one_nat
...
Succ (Succ (Succ (Succ (Succ Zero))))

As an additional style suggestion, you may wish to define a module to organize your code.
module Nat =
struct
  type t = Zero | Succ of t

  let add m n =
    let rec helper m =
      match m with
      | Zero -> n
      | Succ m -> Succ (helper m)
    in
    helper m

  let one = Succ Zero
  let two = Succ (Succ Zero)
  let four = add two two

  let sudan m n p =
    let rec helper m n =
      match m with
      | Zero -> n
      | Succ m -> Succ (helper m n)
    in
    helper (add (add m n) p) one
end

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Home Blogs Junior Ring Savonna Adell: Switching Rings to Achieve Her Dreams
Savonna Adell: Switching Rings to Achieve Her Dreams
Photo © Al Cook
By Rebecca Walton/ Phelps Media Group
There comes a time in every young rider's career that they must make the move from the beloved pony divisions to the Junior Hunters. While some find the transition daunting, 13-year-old Savonna Adell has made it look seamless as she goes from the Medium and Large Ponies, to the Junior Hunters, and has even begun showing the Low Children's Jumpers. The talented young rider carefully manages each of her mounts with the support of her parents, Joelle and Kevin Adell, and her trainer Gary Duffy.
Hailing from Bloomfield Hills, Michigan, the eighth grader shows across the country, kicking off each year at the prestigious Winter Equestrian Festival before traveling north for events like the historic Devon Horse Show, the Lake Placid Horse Shows and the Vermont Summer Classic. No stranger to the best horse shows in the country, Adell will once again be competing at the indoor championships, but this year she will be showcasing her skills in both the Medium and Large Pony Hunters as well as the Junior Hunters.
Savonna & Laugh Out Loud. Photo © The Book Llc
Although Adell began showing in the Junior Hunters in 2017 on her talented mare Redeemed, she went full force into the 3'6″ Junior Hunters at the beginning of 2019 with her new mounts Rockaway and Stolzengraf.
"Horses can be a lot more challenging because they are bigger, stronger and you have to be more precise because you are jumping higher," explained Adell. "It can be difficult sometimes because ponies have smaller strides than horses, so you have to remember that they don't have as much scope and as big of a stride if you're on a pony. If your switching from a pony to a horse you have to remember to open your stride more."
Adell has quickly overcome the challenges posed by changing rings, picking up top awards in both arenas. Her Large Pony Hunter mount Spellbound is currently leading the country, and she has earned several tricolors with Rockaway, Redeemed and Stolzengraf, even topping the Younger Large Junior Hunters at the prestigious Lake Placid Horse Shows with Rockaway.
Savonna & Rockaway. Photo © Anne Gittins
"I have enjoyed switching from ponies to horses because I have to change my ride, which makes me learn more every time," she commented. "Some highlights have been Devon and Lake Placid. Now, I am looking forward for Capital Challenge, the Pennsylvania National Horse Show and the National Horse Show."
Trainer Gary Duffy said, "It was a transition in the beginning, that is what happens when they move off of ponies into the juniors, and they have to realize that and that each horse show is a learning experience when they jump into 3'6″. We have some really good horses though, and Savonna actually skipped over the Children's Hunter division completely, which is a rarity that a rider can do that."
Having a great partner in the ring is crucial to any rider's success, and Adell has worked hard to learn about each of her mounts, which began in the pony ring.
Savonna & Redeemed. Photo © Anne Gittins
"She stepped up to the plate because of the great ponies that she had," said Duffy. "If you have ponies that are not reliable, there is going to be a question when she walks into the junior hunter ring. But each time, it's all about getting the right horses. She has bonded with Redeemed most, that horse is very reliable and manage and negotiate long or short distances and show her the ropes. Savonna was never nervous cantering up to 3'6", she knew that if she was a little deep that the horse would be able to teach her that that is ok. If it was a little long the horses is able to say 'that's OK, I can handle this too.'"
As Savonna successfully made the transition to the Junior Hunters, it became clear that she was ready to test the waters in the jumper ring as well, and she began riding Zanzibar 19 in the Low Children's Jumpers, even winning the Classic at the Skidmore College Saratoga Summer Horse Show. Savonna has enjoyed having the opportunity to compete in both divisions.
"I like them both for different reasons," she noted. "The hunters, you have to be very precise and focus on how you and your horse look. You also have to focus more on your distances. I like jumpers because you have to focus more on your speed and your turns."
Photo © The Book LLC
Duffy added, "I am pretty impressed that she is able to jump from the pony, to the horse to the jumper – that's not a simple task!"
The next step after the jumpers will be the equitation, but Duffy wants riders to take their time getting there. He said, "I want Savonna to feel very confident in doing the smoothness of a hunter track and the technical elements of a jumper course, and then we move into the equitation."
Adell is very focused on being successful in the sport, hoping to do the International Hunter Derbies as a junior, before eventually becoming a professional and hoping to one day represent the United States on the international stage.
For now, Duffy is working with Adell to be successful at each horse show that they attend. "We are working on different lines and turns and just making sure that the horses are prepared for the handy courses," he explained. "We are working on the flatwork to make sure that we can get those under saddle ribbons. Savonna has been pretty much undefeated in the under saddles."
With Indoors right around the corner, Adell and Duffy have to be sure that each horse and pony is ready to showcase their best skills. "We are very excited to go to indoors," said Duffy. "All the riders just have to realize that everybody at that competition is a champion along with themselves, and they just have to relax and realize it's just another horse show at that point."
Adell noted, "The most important lesson that I've learned is that you have to work as a team with your horse and always be appreciative of what they do for you."
That outlook will be part of the key to success at Indoors, where every detail is part of the judging equation, and Adell hopes to bring home top ribbons with her talented group of horses and ponies.
Adell concluded, "My mom has been a great inspiration to me and has taught me not to give up and to work hard for what I want to accomplish, and that is exactly what I plan to do!"
Previous articlePriscilla Denegre and Abby Cole Claim $10,000 WIHS Adult and Children's Hunter Championships
Next articleIHSA Athletes to Compete in the Taylor Harris Insurance Services NHS Adult Equitation Championship
The Working Student: Two Junior Riders Share their Experiences and Offer...

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text:
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The third trailer for Jurassic World: Fallen Kingdom is out, revealing the film's overarching plot, and it looks suspiciously like The Lost World. Universal has been playing a clever game; the first trailer only really included scenes from the first act, and marketing has focused in on that part of the plot too. But there's always been a sense that the trailers were hiding something. The official synopsis, after all, referred to "a conspiracy that threatens the entire planet."
"It was all a lie," Claire shouts in this third trailer. There's a sense in which that's true of Fallen Kingdom's marketing approach. Marketing had bee pointing to the one story, when in reality they had a major twist planned. Sooner or later, though, they were always going to have to change focus and reveal some secrets. This third and final trailer sees the studio hold nothing back. It's clearly an attempt to give viewers a strong sense of what to expect from the film. It's also a justification for the movie's existence, given this franchise started out in 1993. Unfortunately, it also means that the movie is now a lot less secret than it was before.
Early marketing for the film focused on the threat of an impending volcanic eruption. Isla Nubla was revealed to be a volcanic island, one that had awoken after a period of dormancy, and was preparing for a spectacular eruption. The first trailer showed the volcano "clearing its throat," in the early stages of an eruption cycle. That kind of eruption has the power to wipe out all life on the island.
A viral website reinforced this message, suggesting Claire has dedicated herself to ensuring the safety and protection of the dinosaurs. "We must save the dinosaurs," she insisted in one video on the site. It seemed clear that the main plot would be some sort of rescue mission.
But that's what we - and, indeed, Claire - were supposed to believe. It seems the volcano is a red herring; the powerful forces who have funded the rescue mission aren't really interested in saving the dinosaurs at all. Instead, they want to acquire the DNA samples to continue creating dinosaurs - and, indeed, to create a new breed. That's why they're shown diving for the Indominus Rex DNA. But it's also why Blue is so important.
The first Jurassic World movie saw shadowy forces attempt to create dinosaurs as weapons. While they accomplished their goal, they created a horrific creature that could not be controlled. At the same time, though, the film also proved that some dinosaurs can be trained. Owen raised Blue from when she was just a hatchling, and she grew to trust him. So much so that she even fought against the Indominus Rex for him. Velociraptors, it seems, can actually be controlled.
That's vital information for the villains of Jurassic World, including James Cromwell's Benjamin Lockwood. They don't really care about preserving the lives of dinosaurs; they want to acquire dinosaurs as weapons, and they want to create ever-better weapons too. The Indominus Rex was powerful and effective, but they already dreamed of improving on the creature. "Imagine that one, a fraction of the size," Hoskins commented in the first film. "Deadly. Intelligent. Able to hide from the most advanced military technology. A living weapon unlike anything we've ever seen." And, crucially, able to be controlled. That (in theory) is the Indoraptor, the terrifying new creature that's going to be created in Jurassic World 2.
We now know that the film's "big twist" is that the dinosaurs will be sold as weapons. No doubt it's a lucrative business, and the Indoraptor will be their greatest success to date. But, in true Jurassic Park style, it's one thing to create an Indoraptor; it's another thing to control it. The creature will break loose, and go on a rampage across the American estate. That's where the movie will shift tones, becoming darker, more suspenseful, almost Gothic.
It makes sense of the official synopsis, which had already teased that Claire and Owen would "encounter terrifying new breeds of gigantic dinos while uncovering a conspiracy that threatens the entire planet." The danger, no doubt, is that life will always find a way; Lockwood's attempt to auction off dinosaurs as weapons would lead to dinosaurs getting out into the wild. Certainly a recurring "money shot" has been the Indoraptor in a little girl's bedroom, a terrifyingly surreal image that's entirely new to the franchise.
As a "next step" for the Jurassic World franchise, it certainly seems to be a logical one. It's a pretty seamless continuation of the first film, albeit with a few twists in the tale. While the movie won't end with a cliffhanger, writer and producer Colin Trevorrow has described the entire Jurassic World trilogy as one single story. Jurassic World was the beginning, this is the middle, and the third film will be the end. That claim had seemed a little odd, because up until this new trailer, there didn't seem to be a massive thematic throughline between Jurassic World and this sequel. Now, that's changed.
The same character dynamics are in play, including the pivotal relationship between Owen and Blue. Lockwood is cast from the same mold, and have a similar motivation. Conceptually, the films are exploring very similar ideas - ethical questions about how far human beings will go in order to create weapons of war. There's even the straight narrative throughline running from the Indominus Rex to the Indoraptor. Jurassic World 2 is indeed a direct sequel to the first film, more so than it ever seemed from the initial marketing push.


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text:
Fay Vincent
Birthdate 05/29/1938
vs. Owners
Firing Steinbrenner
Debut Year 1989
Year of Induction
Teams MLB, National League
Positions	 Commissioner, Executive
In 1990 Fay Vincent banned George Steinbrenner for life after the Yanks owner paid to find dirt on Dave Winfield; he was reinstated in 1993.
In the collection:
Vincent expresses his dismay of the designated hitter rule
An outspoken critic of the DH rule, Commissioner Fay Vincent expressed his view in an interview with Pat O'Brien during CBS' telecast of Game 4 of the 1991 World Series. In this letter dated March 16, 1992, Vincent writes, "As a traditionalist, I do not favor the designated hitter
An outspoken critic of the DH rule, Commissioner Fay Vincent expressed his view in an interview with Pat O'Brien during CBS' telecast of Game 4 of the 1991 World Series. In this letter dated March 16, 1992, Vincent writes, "As a traditionalist, I do not favor the designated hitter rule. However, the commissioner by himself does not have the power to change such a rule." Strong words from baseball's chief.
Bart Giamatti
Peter Ueberroth
Bowie Kuhn
William Eckert
"Whoever wants to know the heart and mind of America had better learn baseball…"
~Jacques Barzun, 1954
Copyright © Cooperstown Expert 2020
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text:
Questo è un elenco di opere musicali del compositore francese Georges Bizet (1838–1875).

Elenco delle opere

Lavori teatrali
Opere:

 La maison du docteur (La casa del medico), opera comica, 1 atto, (H. Boisseaux; composta sia nel 1867 che nel 1859; mai eseguita)
 Le docteur Miracle (Dottor Miracolo), operetta, 1 atto, (L. Battu & L. Halévy, da R.B. Sheridan; composta nel 1856; prima esecuzione: Parigi, Bouffes-Parisiens, 9 aprile 1857)
 Don Procopio, opera buffa, 2 atti, (C. Cambiaggio, da L. Prividali; composta nel 1858–59; prima esecuzione: Monte Carlo, 10 marzo 1906)
 La prêtresse (La Sacerdotessa), operetta, 1 atto, (P. Gille; composta nel 1861 c.ca; mai eseguita)
 La guzla de l'émir (La guzla dell'emiro), opera comica, (J. Barbier & M. Carré; composta nel 1862 c.ca; mai eseguita)
 Ivan IV, opera, 5 atti, (F.-H. Leroy & H. Trianon; composta nel 1862–65 c.ca; prima esecuzione: Württemberg, Mühringen Castle, 1946)
 I pescatori di perle, opera, 3 atti, (E. Cormon & M. Carré; composta nel 1863; prima esecuzione: Parigi, Théâtre Lyrique, 30 settembre 1863)
 La bella fanciulla di Perth, opera, 4 atti, (J.-H. Vernoy de Saint-Georges & J. Adenis, da W. Scott); composta nel 1866; prima esecuzione: Parigi, Théâtre Lyrique, 26 dicembre 1867)
 Marlbrough s'en va-t-en guerre (Marlbrough va alla guerra), operetta, 4 atti, (P. Siraudin & W. Busnach; composta nel 1867, un atto solo, perso; prima esecuzione: Parigi, Théâtre de l'Athénée, 13 dicembre 1867; il titolo è stato preso dalla popolare canzone "Marlbrough s'en va-t-en guerre")
 La coupe du roi de Thulé (La Coppa del Re di Thule), opera, 3 atti, (L. Gallet & E. Blau; composta nel 1868–69, dopo la sua morte la partitura autografa è stata mutilata da varie mani e rimangono solo frammenti; prima esecuzione: (estratti) BBC Radio, 12 luglio 1955)
 Clarisse Harlowe, opera comica, 3 atti, (Gille & A. Jaime, da S. Richardson; composta nel 1870–71, incompleta; mai eseguita)
 Grisélidis, opera comica, 1 atto, (V. Sardou; composta nel 1870–71, incompleta; mai eseguita)
 Djamileh, opera comica, 1 atto, (Gallet, da A. de Musset; composta nel 1871; prima esecuzione: Parigi, Opéra-Comique (Favart), 22 maggio 1872)
 Don Rodrigue, opera, 5 atti, (Gallet & Blau, da G. de Castro y Bellvis; composta nel 1872, bozza incompleta; mai eseguita)
 Carmen, opera, 4 atti, (H. Meilhac & L. Halévy, da P. Mérimée; composta nel 1873–74; prima esecuzione: Parigi, Opéra-Comique (Favart), 3 marzo 1875)

Musiche di scena:
 L'Arlésienne (La ragazza di Arles), musica di scena, 3 atti (A. Daudet; composta nel 1872; prima esecuzione: Parigi, Théâtre Vaudeville, 1º ottobre 1872)

Opere orchestrali
 Ouverture in la, 1855
 Sinfonia in do maggiore, 1855
 Sinfonia Roma, 1868. Fantaisie symphonique "Souvenirs de Rome" in do maggiore
 Petite suite (cinque movimenti orchestrati da Jeux d'enfants)
 Overture Patrie, 1872
 Suite di Carmen, 1887. Compilò una suite orchestrale utilizzando alcuni brani della sua musica di scena per L'Arlesienne che, dopo la sua morte, Ernest Guiraud mise insieme in una seconda suite L'Arlésienne, anche se comprendeva anche musica da La jolie fille de Perth.

Opere per coro e orchestra
 Clovis et Clotilde (cantata), 1857
 Te Deum, 1858
 Ode Symphony Vasco de Gama, 1859–60

Canzoni
(parole di / anno di composizione)
 L'âme triste est pareille au doux ciel (Lamartine)
 Petite Marguerite (Olivier Rolland, 1854)
 La rose et l'abeille (Rolland, 1854)
 La foi, l'esperance et la charité (de Lagrave, 1854))
 Vieille chanson (Millevoye, 1865)
 Adieux de l'hôtesse arabe (Hugo, 1866)
 Apres l'hiver (Hugo, 1866)
 Douce mer (Lamartine, 1866)
 Chanson d'avril (Bouilhet, 1866)
 Feuilles d'album  (1866): "À une fleur" (de Musset), "Adieux à Suzon" (de Musset), "Sonnet" (Ronsard), "Guitare" (Hugo), "Rose d'amour" (Millevoye), "Le grillon" (Lamartine)
 Pastorale (Regnard, 1868)
 Rêve de la bien-aimée (de Courmont, 1868; dedicata a Léontine de Maësen)
 Ma vie a son secret (Arvers, 1868)
 Berceuse (Desbordes-Valmore, 1868)
 La chanson du fou (Hugo, 1868)
 La coccinelle (Hugo, 1868)
 La sirène (Mendès, 1868)
 Le doute (Ferrier, 1868)
 L'esprit saint
 Absence (Gautier)
 Chant d'amour (Lamartine)
 Tarentelle (Pailleron)
 Vous ne priez pas (Casamir Delavigne)
 Le colibri (Flan, 1868)
 Sérénade 'Oh, quand je dors' (Hugo)
 Vœu (Hugo, 1868)
 Voyage, Aubade, La nuit, Conte, Aimons, rêvons!, La chanson de la rose, Le Gascon, N'oublions pas!, Si vous aimez!, Pastel, l'abandonnée (queste canzoni provengono da opere drammatiche non identificate)

Opere per pianoforte
 Notturno in fa maggiore
 Variations chromatiques de concert (Variazioni cromatiche da concerto; orchestrata da Felix Weingartner in 1933)
 Caprice in do diesis minore
 Caprice in do maggiore
 Chasse fantastique (La caccia fantastica)
 Romance sans paroles (Romanza senza parole) in do maggiore
 Thème brilliant in do
 Valzer in do maggiore
 Trois esquisses musicales (Tre schizzi musicali)
 Grande valse de concert in mi bemolle
 Marine
 Notturno in re maggiore
 Quattro Improvvisi
 Improvviso n. 1, Allegro Moderato in fa minore
 Improvviso n. 2, Allegretto in la bemolle maggiore
 Improvviso n. 3, Andante (tema con varianti) in si bemolle maggiore
 Improvviso n. 4, Allegro Scherzando in fa minore
Chants du Rhin (Canzoni del Reno)
 Quattro preludi
Chansons-Mélodies Romances sans Paroles: Chanson d'Avril, Extase, Méditation : Souvenir de l'Arlésienne
Venise : Romance sans Paroles
 Jeux d'enfants (Giochi di bambini) 12 pezzi per duetto di pianoforte
 L'escarpolette (L'altalena, Fantasia)
 La toupie (La trottola, Improvviso)
 La poupée (La bambola, Berceuse)
 Les chevaux de bois (Cavalli di legno, Scherzo)
 Le volant (Battledore e Shuttlecock, Fantasia)
 Trompette et tambour (Tromba e tamburo, Marcia)
 Les bulles de savon (Bolle di sapone, Rondò)
 Les quatre coins (Il gatto nell'angolo, Schizzo)
 Colin-maillard (Mosca cieca, Notturno)
 Saute-mouton (Cavallina, Capriccio)
 Petit mari, petite femme (Piccolo marito, piccola moglie, Duetto)
 Le bal (Il ballo, Gallop)

Trascrizioni
 Versione per pianoforte solista di tutti e tre i movimenti del Concerto per pianoforte n. 2 di Saint-Saëns

Completamenti di lavori altrui
 Fromental Halévy – Noé, opéra, 3 atti. Libretto di Jules-Henri Vernoy de Saint-Georges; composta dal 1858 al 1862 e lasciata incompiuta alla morte di Halévy. Fu completata da Bizet nel 1865; prima rappresentazione Karlsruhe, 5 aprile 1885.

Note

Bibliografia
 Sadie, Stanley, ed. (1992). The New Grove Dictionary of Opera (4 volumes). London: Macmillan. .
 Dean, Winton (1978). Bizet (The Master Musician Series, 3rd edition). London: J. M. Dent. .

Altri progetti

Collegamenti esterni

Bizet, Georges

redpajama_set_name: RedPajamaWikipedia


text:
Cantonul Montmirey-le-Château este un canton din arondismentul Dole, departamentul Jura, regiunea Franche-Comté, Franța.

Comune

 Brans
 Champagney
 Chevigny
 Dammartin-Marpain
 Frasne-les-Meulières
 Moissey
 Montmirey-la-Ville
 Montmirey-le-Château (reședință)
 Mutigney
 Offlanges
 Peintre
 Pointre
 Thervay

Cantoane în Jura


text:
Dalkeith is an affluent suburb of Perth, Western Australia within the City of Nedlands. The suburb is surrounded on three sides by the Swan River.

History
The suburb takes its name from a cottage built in 1833 by Captain Adam Armstrong and his sons, early settlers of the area who arrived aboard Gilmore. Armstrong, previously the manager of the Earl of Dalkeith's estate in Scotland, named the house "Dalkeith Cottage". The cottage was on a farm bought by James Gallop, who built a two-storey house c. 1872, now known as Gallop House. In 1897 the farm was sold off in lots for residential use. The house was bought by the state government in 1911, and was neglected for several decades before being restored in 1963-4. It is the oldest extant private residence in Dalkeith and the City of Nedlands.

As at 2021, Dalkeith was the most expensive suburb for houses in Western Australia, with a median price of $2.9 million. Jutland Parade is the most expensive street in Dalkeith and considered one of the most expensive streets in Perth.

At the riverside lies Sunset Hospital, built in 1904 and closed in 1995. Several of the buildings are heritage listed. In 2005 the University of Western Australia entered into an agreement with the state government to redevelop the site, including a museum, aged care and residential apartments. In September 2007 UWA withdrew from the agreement, citing delays and restrictions caused by the heritage status of the site.

Secession
In early 2009, residents of Dalkeith formed a movement to secede from the City of Nedlands and form their own local government area, ostensibly the Shire of Dalkeith. The residents suggested secession as economically viable - the Shire of Peppermint Grove, the smallest local government area in Australia, was established in 1895 and currently has about 1,600 residents, whereas Dalkeith currently has over 4,000.

References

Suburbs of Perth, Western Australia
Suburbs in the City of Nedlands


text:
Heriberto Quirós Linton (born 26 July 1972 in Cartago) is a retired Costa Rican football player who played for several teams in the Costa Rican Primera División.

Club career
Nicknamed Chimi, he made his debut in the Costa Rican Primera División in 1993 playing with hometown club Cartaginés and he soon become part of the usuals at the starting line-up and one of the most claimed players.

In 1999, Quirós joined Alajuelense and he moved abroad for a spell with Venezuelan side Trujillanos. In summer 2002 he signed for Santos de Guápiles but a serious knee injury hampered his career with the club, finally leaving them after two years of misery for Carmelita.

International career
Quirós made his debut for Costa Rica in a September 1993 friendly match against Saudi Arabia and earned a total of 7 caps, scoring no goals. He represented his country in 1 FIFA World Cup qualification match He also played at the 1997 UNCAF Nations Cup, taking the place of an injured Sandro Alfaro.

His final international was a November 1997 FIFA World Cup qualification match against Canada.

Personal life
Quirós was born one of 8 children of Violeta Linton Foster and raised in Barrio Fátima, Cartago. He is married to Paula Villalobos. His brother, Luis Quirós, also played professionally for Cartaginés and also his brothers Marcos and Carlos played in the Costa Rican Premier Division.

References

External links

1972 births
Living people
People from Cartago Province
Association football forwards
Costa Rican footballers
Costa Rica international footballers
C.S. Cartaginés players
L.D. Alajuelense footballers
Santos de Guápiles footballers
A.D. Carmelita footballers
Liga FPD players
Costa Rican expatriate footballers
Expatriate footballers in Venezuela
Copa Centroamericana-winning players


Universities focus on scientific research and the education they provide is based on it. Doctoral programmes are offered by universities.
Check out the below map of Finland to see where you could be studying!


Rare incredibly intricate antique Edwardian muslin and mixed lace lawn dress, dating back to the 1900s. Very unique with a slight balloon sleeve. Original buttons and hook and eyes for closure. Incredible workmanship, all hand done. This garment was found in a trunk which was unopened since 1926, and appears unworn. Could be worn as a wedding dress.
NOTE: Button holes could easily be moved over to accommodate for a larger bust and waist, or more hook and eyes added, this would allow for about 2" more inches of room.


Mrs. Betty-Oh what a wonderful lady. She is an inspiration to all. We have enjoyed many years of great times with her and Jim. They were always so sweet, so caring. Always taking care of others. We will truly miss Betty. She was always taking care of animals and loves cats. While our children were growing up the Tally's made a great impression on our children and she became known as Mrs.Tally who lives down the alley. She always had kind words and loved to tell a joke or two. She loved to tell us stories of their life together and her childhood. Growing up in the Catholic Church and being raised by her grandparents. She would tell us of her days of BBQ's - a steak for Jim and a hamburger for Betty. Oh the blessings, time and stories she could tell. She always asked about our families and our children. Thank you Betty for so many wonderful years. We know that God truly blessed us with her presence here on earth. Just to let you know that our son Kevin is having a mass said for her in Midland. Our prayers are with you all, Jimmy, Darlene and Maureen and extended families. May God bless you and keep you always. The Lenius family!
We will miss Ms Betty dearly, She was a great grandma who adopted us the Martinez kids and she was bless she left peacefully to be with her Jimmy.
Condolences to Mrs. Betty Tally's family. You are in my thoughts and prayers. James & Betty lived across the street from my grandma. I can remember when I was little, we would go over to visit Mr. & Mrs. Tally. Mrs. Tally would always offer us a soda pop and let us watch cartoons. As a child that was a wonderful memory of mine. She was so caring and always thought of others. It was apparent, how much she loved her friends and family. She will be greatly missed. We love you Miss Betty.
I have so many fond memories of Mrs. Betty Tally. She was so loving and caring for my family, and I used to love going over to her house when I was kid. It was tradition to go over and she would give my brother and I a Coke, an ice cream treat, and a dollar. She would talk and listen to us while we enjoyed our snacks and probably most importantly she taught us the importance of grammar and manners. (She would always tell me "Don't say that you're done! You're not a cake!") :) I have always regarded her as another grandmother and I loved her so much! She will be so dearly missed. She would always talk about her family and it was obvious she loved you all so much. My condolences for your loss.
Your mother was a great friend to my mother. They loved each other and always enjoyed visting over a cup of coffee. She was so thankful she was able to go to your mom's last birthday party here in Abilene. I know you will miss her.
Prayers for your family. She was amazing lady. I have alot of memories growing up as a kid with Betty and Jim.


School Lunches - To book school lunches; please print off the form below and bring into the school office together with payment.
Medicines - Should you need us to give your child prescribed medicines or ointments, please complete the "Head Teacher Agreement to administer Medicines Form" and bring into the school office. Please remember that all medicines should be in the original packaging, in date and with the original pharmacy label attached.
Application for pupil leave of absence from School - Please print off the form below and bring to the school office.


text:
Name: Bracy, Terry
Current Position: Previous Chairman
Terrence Bracy has been the only Chairman of the Foundation. Bracy's father, Webb Brennan Bracy, taught English Literature and also wrote jokes for comedians Bob Newhart and Henny Youngman. Terrence Bracy received a B.S. from St. Louis University with a double major in Political Science and Creative Writing in 1964 and a Master of Arts in Government from the University of Arizona in 1966. During graduate school, from 1965 to 1966, he was News Editor at KVOA, the NBC affiliate in Tuscon, Arizona, and from 1964 to 1966 he taught courses in American Government at the University of Arizona. From 1966 to 1976 he was a Legislative Assistant to Congressman Udall, and also worked on Udall's unsuccessful run to become the Democratic candidate for the presidency in 1976. In January 1977 incoming Secretary of Transportation Brock Adams appointed Bracy to the post of assistant secretary fpr Congressional liaison. In July 1977, Bracy resigned, along with his immediate superiors, Adams and deputy secretary Alan Butchman. In 1982 Bracy co-founded the lobbying firm, Bracy, Williams & Company, now Bracy Tucker Brown & Valanzano, where Bracy is the Chief Executive Officer. His clients have included Phelps Dodge Development Corporation, the cities of Tucson, St. Louis and Atlanta and the Canadian National Railroad. In 1984, Bracy worked on the presidential campaign of Democrat Gary Hart. Bracy was a member of the board of trustees of the Grand Canyon Trust when President Bill Clinton named him to the board of trustees of the Morris Udall Foundation in 1994, and Bracy was elected its Chairman.
Bracy is a long-time contributor to both the Democratic and Republican Parties. Among the Democrats he's contributed to: For President, Bill Bradley, Richard A. Gephardt, and John Kerry; for Congress, Bill Anoatubby, Oklahoma; David Bonior, Michigan; Norman D. Dicks, Washington; Karan English, Arizona; Raul M. Grijalva, Arizona; Edward L. Pastor, Arizona; Tom Udall, New Mexico; For Senate, Charles S. Robb, Virginia, and Mark E. Udall, Colorado. The Republicans to whom he's made contributions are: For Congress, Lisa Ann Atkins, Arizona; Kay Granger, Texas; James T. Kolbe, Arizona; and Donald E. Young, Alaska.
Udall Foundation


text:
title: Történet
date: 04/11/2022
---

#### FORDÍTSD ODA A MÁSIK ARCODAT IS

_Írta: Rick McEdward_

Omar egy közel-keleti egyetemre járt és munkára volt szüksége, de bármire nem volt hajlandó azért, hogy alkalmazzák. Az állásinterjún nyíltan elmondta, hogy szombaton nem dolgozik, mert ez Isten szent napja. A cég képviselője szemrebbenés nélkül elküldte: "Rendben. Nincs szükségünk magára." Abban az országban nagy a munkanélküliség, igen nehéz munkát találni.

Omar csupán napokkal korábban adta át életét Jézusnak. Hat éven át járt a közösségbe és tanulmányozta a Bibliát, mielőtt meghozta a döntést. Miután elbocsátották, vásárolt egy háromkerekű kocsit, és azt tervezte, hogy szezámmaggal beszórt kör alakú kenyér, simit árusításával fog pénzt keresni.

Omar szombattartó barátait megérintette a Jézus melletti hűséges kiállása, és imádkozni kezdtek érte.

Néhány nappal később a cég felhívta, és felajánlották neki az állást, szabad szombattal. Omar annyira hálás volt, hogy eldöntötte, minden nap találni fog egy embert, akinek Krisztusról beszélhet.

Néhány nappal később egy kávézóban italát szürcsölgetve beszédbe elegyedett egy idősebb férfival. Omar elmesélte lelki útjának történetét a családi szent könyvtől a Bibliáig és azt, hogy igazi békére lelt. Miután elhagyta a kávézót, egy férfi, aki hallotta a beszélgetést, ordítozva követte: "Nem hiszem, hogy ilyeneket tudsz mondani! Nem szégyelled magad?!" A férfi ütni kezdte Omart az öklével.

_Amikor szombattartó barátai videón felhívták, feldagadt szemekkel, de széles mosollyal köszöntötte őket. "Hívhattad volna a rendőrséget" – mondták neki. "Igen – mondta Omar –, de Jézus azt mondta, hogy fordítsuk oda a másik arcunkat is."_

redpajama_set_name: RedPajamaGithub


text:
Q: JavaScript Isotope Gallery - two active tabs? I am trying to load two Isotope galleries on my website (two separate pages) but only have one JavaScript function running the gallery.
The first gallery is working fine but the second one does not show anything until one of the tabs is clicked.
Here is my code:
$(function() {
    var filterList = {
        init: function() {
            $('#portfoliolist').mixItUp({
                selectors: {
                    target: '.portfolio',
                    filter: '.filter'
                },

                load: {
                    filter: '.shute',
                    filter: '.jab'
                }
            });
        }
    };

    filterList.init()
});

The second gallery is filter: '.jab', why won't this load on default when the .shute one does?
Thanks.

A: Try using filter: $('.shute, .jab') instead of defining filter twice.
Code:
$('#portfoliolist').mixItUp({
  selectors: {
    target: '.portfolio',
    filter: '.filter'
  },

  load: {
    filter: $('.shute, .jab')
  }
});


Did you play Telephone as a child? You know, the game where you whisper a word or phrase in someone's ear, and then they repeat it to the closest person? If so, you know that by the end of the game, the original word or phrase changed dramatically.
That's exactly how the chief learning officer (CLO) of a transportation company described training prior to purchasing and fully implementing Paycom Learning.
Providing comprehensive, world-class training to 700 employees – including nearly 650 truck drivers – across 14 locations in different states proved to be a tough task. The CLO was responsible for creating, organizing and tracking trainings for employees nationwide, relying on managers at each location to conduct the sessions.
Tracking attendance was a manual process. Employees had to complete a sign-up sheet that was later submitted by their manager to company headquarters. However, tracking course completion is crucial to remaining compliant, especially since such instruction is mandatory for companies that transport fuel and hazardous chemicals.
That's when the CLO discovered Paycom Learning.
"Instead of being consumed by the day-to-day planning and tracking, Paycom Learning allows me to take a step back and focus on the strategic areas of my job that directly affect growth and success," she said.
With Paycom Learning, the company was able to significantly up-level their existing training process. The learning tool allows the company to create and offer courses eight times faster than before, saving over 20 hours per course.
Additionally, Paycom Learning's built-in courses, free with the purchase of the tool, gave the CLO freedom to focus on creating courses specific to the transportation industry, as opposed to foundational topics, such as harassment prevention, cybersecurity and more.
Best of all, Paycom Learning allows the CLO to provide consistent training to all employees at all locations, allowing her the ability to do her job at a more strategic, more meaningful level.
Learn more by reading our case study or registering for our free webinar, featuring the transportation company's CLO.
As Paycom's client marketing specialist, Monica Johnson utilizes a mixture of marketing and human capital management knowledge gained from years of industry experience. A graduate from the University of Central Oklahoma, Johnson has been with Paycom since 2013 and has served in numerous roles during her career with the company. In her spare time, she enjoys baking, exploring Oklahoma City and sipping coffee, while reading a good book, at one of her favorite local shops.


Subject: Re: Best Cover Art?
I haven't seen this discussed here before, so I'll ask: Which Beatles album do you think has the best art on the album cover?
for its best recreation of the spirit of a movie: Capitol's Help!
for its lack of truth-in-advertising: Capitol's "butcher cover'"
for its ignorance on semaphore signals: Help!
for its period recreation look: Live At The BBC!


A secret recipe isn't a fun should youn't have wonderful friends that it is possible to share it with! The great thing is there are several very delicious vegan recipes you could prepare easily with minimal work. The rest of the dishes must be put in the dishwasher, or they have to be washed by hand. This recipe is created in a conventional cast iron skillet. The ideal recipe is tough to find. Occasionally it's the basic recipes that our family members enjoy the most.
Peanut butter, in addition to being a tasty snack, is additionally a healthy one. Also, make certain you don't have a peanut allergy! Peanut butter also have the nutritious fats and potassium which helps prevent heart attacks! So peanut butter and marshmallow creme isn't the most healthy thing on earth, it's still amazing. So if you prefer to understand the way you can make bread pudding the old-fashioned style, then here are a few fantastic recipes to help you with your way. The secret to a superior bread isn't to over mix it.
It is possible to use dried or candied fruits like cranberry, apricots, etc., too, to increase the variety. It makes an excellent, clean-tasting banana bread. It's the very best banana recipe I have ever used and it's so easy!


text:
WORK CONTINUES ON SOUTH FRIGATE BAY BEACH ENHANCEMENT PROJECT, SAYS MINISTER OF TOURISM
in Featured, In The News
Basseterre, St. Kitts, January 16, 2020 (SKNIS): The joint effort between the Government of National Unity and the CARICOM Development Fund (CDF) has seen the steady refurbishment of the popular area at South Frigate Bay known as "De Strip".
Minister of Tourism, the Honourable Lindsay Grant stated during the Prime Minister's Press Conference on January 15, that work on the area has progressed at a steady pace as "the CDF is a stickler for process and procedure. Because of that, it has taken longer than anticipated for the funding sometimes to materialize."
"As recently as in December of 2019, we have put in for the funds by CDF, their portion of funds, over the Phase One of the project, which will enable us again to ramp up the project," said Minister Grant. "If you have driven over there recently you would realize that people are back to work on the project."
Minister Grant stated that the project consists of two components, the landside and the seaside.
"Right now we are working on the landside, which involves the entrance area, the exit, and the bathrooms on the side to the pond. We fixed up the road already," said the minister.
The tourism minister stated that the entrepreneurs at "De Strip" appreciate the work that is being done and have "stepped up their game."
"If you have gone over there recently you've seen new bars, refurbishment of bars [all] anticipating the kind of business that they will generate in the not too distant future," he said.
Minister Grant said that a lot of work is also being done on the effluent at the site.
"That has been an issue over 20-30 years where the effluent has not been properly disposed of," he said. "We are ensuring that in this environmentally friendly world that we are in that we make sure that we dispose of the effluent in a proper manner. And that is being done. You won't see it physically from the top but we are going to connect into the Marriott system and that is taking us a significant amount of money. It's going to take us over a million dollars to make sure that is done."
In terms of the seaside, Minister Grant said that work will commence there shortly.
"We had some marine engineers in from Jamaica over the last eight months who would have done some surveys in terms of the waves and wind action in terms of the seaside," said the Minister of Tourism.
The minister stated that Frigate Bay is losing some of its beach and the project will ensure that the beach is not lost altogether.
"So we have done that wind and wave action survey by the marine engineers over an eight month period," he said. "We are now going to begin the work on the seaside in terms of putting in groins and breakwaters to ensure that the beach comes back and then we put in the boardwalk, which we intended to do."
The Minister of Tourism stated that the Government of National Unity is committed to ensuring that the project finishes in 2020 and so far is on pace with the project.
MORE HOMES BEING DELIVERED TO THE PEOPLE OF ST. KITTS AND NEVIS UNDER A TEAM UNITY ADMINISTRATION
ST. KITTS AND NEVIS GOVERNMENT'S STEWARDSHIP YIELDS SIX YEARS OF CONSECUTIVE ECONOMIC GROWTH


Before the snow melted Emily, Nadeau, and I made a run to Lumpy Ridge to try a few old school classics, this might be the hardest "V7" I've ever done... Embrace the Sandbag People! This is a classic!
Left Angry Man V7++, Lumpy Ridge, CO from Paul Dusatko on Vimeo.


Get a superior clean with Electrolux's Intensive Wash dishwasher setting that gives you spotless dishes each time. Get clean dishes fast without wasting water and detergent with the QuickPlus 30 Minutes program and the Half Load Option.
The Intensive wash program ensures your dishes come out squeaky clean. Get spotless clean dishes always.
Get clean dishes in 20 or 30 minutes with the QuickPlus program. Perfect for lightly soiled dishes.
One of the most energy efficient dishwashers in the market today.
With this option you can wash a small load of tableware and cookware in shorter duration, saving you water and energy.


text:
ERs open for emergencies during pandemic
TUCSON – Hospital emergency rooms in southern Arizona are open, and doctors want the public to know that delaying emergency treatment can result in additional health complications, especially in the case of heart attack and stroke.
"It's important we let our community know that we are still here and ready to care for those who need medical attention. Accidents and medical emergencies don't stop from happening at any moment, even during the coronavirus pandemic," says Dr. Merlin Curry, Emergency Services Medical Director at Carondelet St. Joseph's and St. Mary's Hospitals.
"No one should be delaying the care that they need, patients should feel reassured that our associates are ready and safe to help them," explains Dr. Curry. "We are here for our community, as we were before the COVID-19 pandemic and will continue to provide compassionate and expedited care to all of those who need it."
Q: Are the emergency rooms at Carondelet hospitals open?
A: Most definitely. Yes.
Q: When should patients come to the ER?
A: Don't delay care if you or a loved one have symptoms that are best evaluated in an emergency room. Call 911 if think a heart attack or stroke is suspected. Examples of things that need emergency care include broken bones, cuts that may require stitches, head or eye injury, shortness of breath. The key is that you don't wait when you think you are having an emergency.
Q: How does the hospital ensure the safety of ER patients?
A: We screen all people coming to our facilities and limit entry to the hospital, and have enacted visitation restrictions. Our medical professional screeners ask a set of questions and check the temperature on everyone entering the hospital. Anyone that meets potential COVID criteria is immediately isolated to protect everyone in the hospital.
Q: If a pregnant woman is close to her delivery date, can she go to the ER if she's having contractions?
A: Yes, she most certainly can. If not an emergency we encourage coordinating with your obstetrician.
Q: How can patients protect themselves from COVID-19 exposure if they need to go to the ER?
A: We have plenty of masks, hand sanitizer, hand soap, space and isolation rooms to keep our patients safe. If waiting to enter the facility, please try to keep six feet apart and wear your home mask if possible. I have yet to see a significant line at any entry point at any of the Carondelet facilities.
Q: Can a patient bring a companion in the ER?
A: Only in certain circumstances, if they are a parent/guardian, in emergency end of life events and when a patient cannot provide a history for themselves. We are limiting visitation to protect the community and our patients.
Q: Can a parent accompany their child to the ER?
A: Yes. Typically, only one parent is allowed at a time to reduce risk of transmission.
Q: If a patient has COVID-19 symptoms, can he/she go directly to the ER?
A: Yes, they can go directly to the emergency department. If possible, we ask that you wear a mask when you are traveling to the ER. We encourage you to come when you have shortness of breath, high fever that doesn't respond to acetaminophen or ibuprofen, dizziness, confusion or other symptoms that are concerning.


Iran Health International which will be held in conjunction with several National Medical workshops, is a comprehensive fair which covers Following domains :Medical, Dental, Laboratory Equipment, Pharmaceutical Products & Health care Services. Held this year for the 18th time, the exhibition enjoys a high reputation both in Iran and Middle East. Iran Health is proud of being able to offer your business a unique opportunity and look forward to the pleasure of having your products on display at its forthcoming session.


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As Dr. Will Caster works toward his goal of creating an omniscient, sentient machine, a radical anti-technology organization fights to prevent him from establishing a world where computers can transcend the abilities of the human brain.
So, my expectations for this film have gone from extremely high (due to Wally Pfister's great cinematography work with Christopher Nolan, and a good cast and sci-fi premise) to fairly subdued (a terrible trailer campaign that not only seemed to give away the plot, but managed to ruin the allure, and a hefty critical panning) but I was pleased that this turned out to actually be a really good sci-fi film. It takes the idea of self-aware machines, a central premise that has been done to death in sci-fi films, but manages to put a fresh spin on it and create a story that isn't only thrilling, but is also romantically involving. The story focuses primarily on Dr Will. Caster (Johnny Depp), a researcher focused on artificial intelligence and the idea of machines as sentient beings (an idea he refers to as Transcendence), his wife (Rebecca Hall) and colleagues (Paul Bettany, Morgan Freeman). Things kick into gear fairly early on, when a terrorist group attack several research facilities and attempts to assassinate Caster, initially not fatally, but it becomes so due to radioactive material in the bullet (which only makes sense from a storytelling perspective, but hey ho, we'll let that go).
The trailers were fairly clear that the story involves Caster's consciousness being uploaded to a machine, and the central conflict involves the 'machine' becoming more powerful throughout the course of the film. Like many great sci-fi films, the narrative poses interesting questions about what it means to be human and about the extraordinary power of machines. Whilst the aspect of powerful machines is nothing new, the romance aspect between the machine version of Caster and his wife is fairly fresh (despite 'Her' earlier this year) and this adds a greater level of depth to the film thanks to excellent performances from Depp and Hall. Depp is great in a 'straighter' role following various turns as crazed weirdo's in a variety of Tim Burton films and the Pirates of the Caribbean series, but it's Hall who steals the plaudits, strongly depicting her characters inner conflict as she struggles to marry up her love for her husband, and the danger posed by the new situation. The supporting cast is strong as well, filled with great actors such as Bettany, Freeman, Kate Mara and Cillian Murphy.
As you would expect from Pfister's cinematography background, the film is a visual treat, and the sequences involving effects truly stand out. The difficulties perhaps comes with the narrative, which initially struggles to generate momentum but it does click into gear as we approach the third act, which is very strong, albeit I could have done without the final 5 minutes which seemed to put too fine a point on the film's main themes. Overall though, this is an intelligent and well intentioned piece of sci-fi and I'd urge anyone reading this not to let the critical lashing put you off – Transcendence isn't perfect but there's a great deal to enjoy here.
Starring: Johnny Depp, Rebecca Hall, Paul Bettany, Cillian Murphy, Kate Mara and Clifton Collins Jr.


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text:
A Fresh Look at Monoamine Oxidase Inhibitors for Depression
Issues in Adherence to Treatment With Monoamine Oxidase Inhibitors and the Rate of Treatment Failure
Lawrence J. Cohen, PharmD, BCPP, FASHP, FCCP, FCP, and David A. Sclar, BPharm, PhD
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In 2000, the economic burden of depression in the United States was estimated to be $83.1 billion. Although many effective treatments are available and treatment rates have increased, response and remission rates for patients with depression remain low and multiple treatment trials are often required. Whether patients are adherent to their medication affects response and remission rates, and nonadherence is common among patients with depression. Increasing adherence improves treatment outcomes and lowers treatment costs. Interventions that increase adherence include educational, behavioral, affective, and provider-targeted strategies; transdermal delivery of drugs also may increase adherence by simplifying the patient's medication regimen. While monoamine oxidase inhibitors (MAOIs) have proven efficacy for depression, particularly for patients with treatment-resistant or atypical depression, they are underprescribed due, in part, to concerns over dietary and drug restrictions that are required to avoid potential serious side effects. However, newer MAOI formulations, including a transdermal delivery system, have improved safety and tolerability profiles and avoid or lessen the need for dietary restrictions, giving clinicians another option for treating patients who may be nonadherent or nonresponsive to their current antidepressant.
(J Clin Psychiatry 2012;73[suppl 1]:31-36)
From the Department of Pharmacotherapy, the Department of Health Policy and Administration, and the Pharmacoeconomics and Pharmacoepidemiology Research Unit, Washington State University College of Pharmacy, Spokane (Drs Cohen and Sclar); the Washington Institute for Mental Health Research and Training, Spokane (Drs Cohen and Sclar); and the Department of Pharmacotherapy, University of North Texas Health Science Center, Fort Worth (Dr Cohen).
This article is derived from the planning teleconference series "A Fresh Look at Monoamine Oxidase Inhibitors for Depression," which was held December 2011 through February 2012 and supported by an educational grant from Mylan Specialty L.P. (formerly known as Dey Pharma, L.P.).
Dr Cohen is a consultant for Dey and has received honoraria from and is a member of the speakers/advisory boards for Sunovion and Merck.
Dr Sclar is a consultant for and has received grant/research support and honoraria from Eli Lilly, Pfizer, GlaxoSmithKline, Forest, Dey, and Bristol-Myers Squibb and is a member of the speakers/advisory board for Eli Lilly.
Corresponding author: Lawrence J. Cohen, PharmD, BCPP, FASHP, FCCP, FCP, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107 (lawrence-cohen@att.net).
doi:10.4088/JCP.11096su1c.05
© Copyright 2012 Physicians Postgraduate Press, Inc.
Although many options are available for treating patients with depression, remission rates remain low and recurrent episodes and chronic subsyndromal symptoms are common.1-3 In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study,1 only about a third of patients reached remission after an adequate trial of a first-line antidepressant, and another third still had not reached remission after 4 treatment steps.
Monoamine oxidase inhibitors (MAOIs), developed in the 1950s, have demonstrated efficacy for treating depression, particularly atypical and treatment-resistant depression.4 MAOIs were once the mainstay of treatment, but their use began to decline in the 1960s after rare but serious hypertensive events were observed. The cause of these events was determined to be an interaction between MAOIs and tyramine, a trace amine found in some foods.5 Patients taking MAOIs must therefore follow dietary restrictions, and, although these restrictions have been simplified over the years, both patients and clinicians have viewed them as burdensome.6 By the end of the 1990s, after the introduction of selective serotonin reuptake inhibitors (SSRIs) and other newer antidepressants with better tolerability profiles, only 2% of clinicians reported prescribing MAOIs frequently, even though a majority believed they were useful for treating depression.7
Due to the need for dietary restrictions and the risk of potentially serious side effects from food and drug interactions, treatment guidelines8,9 typically recommend older MAOIs as third- or fourth-line treatments, although they do note that they may be considered earlier for patients with atypical or treatment-resistant depression. However, newer MAOI formulations with improved safety profiles have been recommended as first- and second-line treatments and provide another treatment option for patients with treatment-resistant depression.10
Treatment Adherence and Illness Outcomes
Lack of therapeutic response to an antidepressant may be due to treatment resistance, in which, despite taking the medication as prescribed at an adequate dosage for an adequate duration, the patient receives little or no symptomatic improvement. However, nonresponse may also be due to nonadherence, in that the patient has not followed the antidepressant regimen, irrespective of initial response to the agent, and, therefore, his or her depression appears to be treatment resistant.
For Clinical Use
Adherence to an antidepressant affects treatment response and remission rates for patients.
Patients who appear to be treatment-resistant may be experiencing treatment failure due to nonadherence.
Multifaceted strategies employing educational, behavioral, affective, and provider-targeted strategies enhance treatment adherence.
A transdermal MAOI formulation may help to address adherence barriers for patients with treatment-resistant or atypical depression.
Adherence refers to compliance with day-to-day treatment instructions (eg, timing, dosage, frequency), while persistence pertains to continuing to take the medication for the duration prescribed.11 Treatment adherence and illness outcomes are strongly correlated: response and remission rates are significantly higher and time-to-recurrence rates are significantly longer for patients who adhere to their medication regimens than for those who do not.12
Nonadherence can negatively affect treatment outcomes, whether the patient takes too much medication or too little. If patients unintentionally miss doses or purposefully take a drug holiday, they may experience discontinuation symptoms or nonresponse. Extra doses may result in increased adverse effects, which may lead patients to discontinue treatment. Adherence is also associated with persistence: patients with lower adherence rates discontinue treatment more frequently than those who adhere day-to-day to their medication.13
Adherence Rates in Depression
Unfortunately, adherence to treatment is poor among patients with depression. In one 9-week trial,13 50% of patients taking antidepressants had at least 1 drug-free interval lasting 2 or more consecutive days, while 19% had at least 1 drug holiday lasting 4 or more consecutive days. Conversely, 67% took too many pills at least once. The risks for overconsumption and underconsumption occurred during specific time courses over the trial, with the risk for taking too many pills decreasing over time and the risk for taking too few increasing over time.
Adherence rates have also been shown to vary for different classes of antidepressants. A large retrospective database analysis14 (N = 266,665) found that only 12.4% of patients taking an older MAOI or a tricyclic antidepressant (TCA) were adherent to their medication over a 6-month period, compared with 29.3% of patients taking an SSRI and 33.6% of patients taking a serotonin-norepinephrine reuptake inhibitor (SNRI). The transdermal MAOI selegiline was not included in the database, but adherence rates in the published acute clinical studies15-17 for the drug ranged from 94% to more than 98%, while 84% of patients in a 52-week double-blind trial were adherent.18 Trials comparing transdermal and oral therapies for illnesses such as Alzheimer's disease and hypertension have shown greater adherence rates among those using the transdermal patch.19,20
Persistence rates are also low with antidepressant treatment. Nearly one-third of patients treated for depression discontinue their antidepressant in the first month of treatment,21 and more than half stop taking prescribed medication by 6 months.22 Further, more than 60% of those who stop antidepressant treatment do so without consulting their physicians.22
Economic Consequences of Nonadherence
In 2000, the economic burden of depression in the United States was estimated to be $83.1 billion, an increase of 7% from 1990 ($77.4 billion in inflation-adjusted dollars).23 However, in that decade between 1990 and 2000, the treatment rate for depression increased by 56%. One reason that the overall dollar figure increased so little compared with the expansion of the treatment population is that inpatient care decreased from 17.3% of the total costs in 1990 to 10.7% in 2000. During that time, there was a 5-fold increase in dollar sales of antidepressants (Figure 1).23 Using this lower-cost form of care has made it possible to treat larger numbers of patients without proportionally increasing the economic burden.
Click figure to enlarge
The effect of antidepressant treatment on total costs, however, depends on several factors. Stability of treatment is one factor: patients who remain on their initial antidepressant have lower annual per patient costs than patients who discontinue or switch antidepressants, possibly because switching from or discontinuing an antidepressant can be associated with increased outpatient care and hospitalization.24 Patients taking older MAOIs and TCAs have significantly higher therapy change rates than patients taking newer antidepressants (P < .001) and correspondingly higher health care utilization.14 Therefore, both efficacy and tolerability should be considered when choosing an antidepressant for an individual patient; even the use of a more expensive drug over a less expensive drug may lower overall costs if the patient's adherence/persistence is increased and health care utilization due to unresolved depression is decreased.25
Depression is projected to be the second-leading cause of disability by 2020.26 The World Health Organization (WHO) has recognized the importance of treatment adherence in improving outcomes, enhancing patient safety, and reducing economic burden and has designated depression as 1 of 9 chronic conditions on which efforts to improve medication adherence should be focused as a means of improving treatment outcomes.27 Improved treatment response and higher remission rates would lower the burden of depression to society by reducing both direct health care costs and indirect costs, such as decreased work productivity, while increasing quality of life for patients.28,29
Enhancing Treatment Adherence
Data indicate that the primary predictors of nonadherence to antidepressants include unpleasant adverse effects, a lack of patient education about the illness and treatment, and a poor relationship between the physician and the patient.30 Systematic reviews31,32 conducted to identify interventions that improve adherence have generally been inconclusive, signifying a need for carefully designed clinical trials on the effects of single and combined interventions. A trend toward greater adherence rates was found in treatment groups who received more interventions,31 suggesting that multifaceted strategies best enhance adherence. An analysis32 of 23 narrative reviews that recommended interventions to improve adherence found that only 23% of the recommendations were supported by evidence from randomized controlled trials or meta-analyses. The most commonly recommended interventions were patient education, a strong patient-physician alliance, family education, clinical management strategies (eg, routinely see patients often during initial treatment), proactive management of side effects, and a simplified treatment regimen. The best evidence-supported interventions were side effect management and preference for SSRIs; the preference for SSRIs was supported by meta-analyses that indicated that the fewer side effects experienced with SSRIs than with other antidepressants allowed for fewer dropouts from treatment.
In a review of randomized controlled trials, Vergouwen and colleagues33 classified interventions to improve adherence into 2 broad categories: patient education and collaborative care. Forms of patient education varied among the studies and consisted of verbal information about side effects, leaflets handed to the patient and explained at the visit, personalized mailed literature, or a combination of these methods. Collaborative care interventions entailed physicians and other mental health or primary care professionals employing multimodal methods to improve adherence (eg, increased visits, increased education, monitoring of medication use, and patient support provided by nurses). The review of the effectiveness of these interventions found no clear benefit in the aggregate for patient education alone on adherence or treatment outcomes. However, 9 of 11 collaborative care studies demonstrated improvements in adherence and better depression outcomes.
Chong et al34 reviewed 26 studies to determine the effectiveness of educational, behavioral, and multifaceted interventions in improving antidepressant adherence and treatment outcomes (Figure 2). The majority of the 5 education studies employed mailed materials; none reported an increase in adherence or persistence among participants. The single behavioral study employed a psychosocial intervention to identify and address barriers to adherence, and improvements in both adherence and outcomes were reported. The 20 studies of multifaceted interventions employed a variety of educational, behavioral, affective, and provider-targeted components. Most multifaceted strategies focused on care management and patient follow-up, which involved collaboration among allied health professionals, psychiatrists, primary care physicians, and pharmacists. Of the 22 multifaceted interventions used in the 20 studies, 15 interventions produced positive effects versus usual care for adherence outcomes or for both adherence and depression outcomes. Each intervention that included pharmacy refill monitoring demonstrated increased adherence to antidepressants. However, pinpointing the specific components of multifaceted interventions that most effectively contribute to improved adherence and outcome will require more research.
Lin and colleagues21 looked at predictors of adherence to antidepressant therapy and determined that patients were more likely to adhere to medication during the first month of treatment when they received 5 specific educational messages: (1) to take the medication every day, (2) to not expect efficacy before 2 to 4 weeks, (3) to keep taking the antidepressant even when feeling better, (4) to check with the physician before stopping the medication, and (5) to ask questions regarding the medication using a provided contact. Subsequently, Lin et al35 determined that significantly increasing a patient's favorable attitude toward antidepressant medication and their self-confidence in managing medication side effects was associated with greater adherence to long-term pharmacotherapy.
Finally, a comprehensive review36 of the literature on psychiatric medication adherence noted that evidence supports cognitive-behavioral strategies and motivational interviewing as approaches to improve adherence. Other interventions also recommended included strengthening the therapeutic alliance, specifically addressing medication adherence during treatment visits, assessing the patient's motivation to take the prescribed medication, and identifying and addressing his or her potential barriers to adherence.
Transdermal Delivery and Treatment Adherence
Transdermal formulations of drugs are delivered directly into the circulatory system, thereby avoiding the gastrointestinal system and the hepatic first-pass effect. Transdermal delivery systems have been developed for a variety of drugs that treat neurologic conditions, including rivastigmine for Alzheimer's disease and dementia due to Parkinson's disease, rotigotine for Parkinson's disease and restless legs syndrome, the selegiline transdermal system for major depressive disorder, and the lidocaine 5% patch for pain from postherpetic neuralgia.37 Delivering medication transdermally has both practical and pharmacokinetic advantages over oral delivery that may increase treatment adherence.
While oral medications produce a rapid peak in plasma levels that then rapidly declines, skin patches provide a smooth and continuous delivery of the medication.37 Keeping drug levels within the therapeutic range may increase efficacy while decreasing adverse events owing to fluctuations in plasma levels. Additionally, transdermal formulations are generally applied once a day, which can simplify dosing regimens for patients who need to take more than one medication per day. Transdermal patches can be used by incapacitated patients or by patients with swallowing problems. Another advantage is that the patch is a visual reminder for patients to take the medication, and caregivers can also see that the medication is being used. Transdermal delivery is rated highly in patient satisfaction, and caregivers prefer patches to capsules, in part due to their ease of use.38,39
One disadvantage of the transdermal patch is that 20% to 50% of patients will have a skin reaction at the application site.40 Most commonly, these reactions consist of a localized redness or itching, sometimes with edema; symptoms are typically mild to moderate, temporary in duration, and disappear spontaneously within several days following patch removal. Application site reactions are usually a form of irritant contact dermatitis and can be minimized by rotation of the application site, careful removal of the patch, and the use of moisturizers and topical corticosteroids.
Selegiline Transdermal Delivery System
In addition to metabolizing excess neurotransmitters in the brain, monoamine oxidase (MAO) metabolizes dietary tyramine during digestion. Inhibiting MAO in the gut can allow excess tyramine to enter the circulatory system, where it triggers norepinephrine release. An excess accumulation of norepinephrine then causes a rapid increase in blood pressure, which can lead to hypertensive crisis. Therefore, patients taking older oral MAOI formulations must follow dietary restrictions to avoid excessive intake of tyramine, and these restrictions are one of the most frequent reasons clinicians cite for not prescribing MAOIs.7
The transdermal formulation of the MAOI selegiline is delivered directly into the circulatory system and thus leaves MAO-A in the gut largely unaffected (Table 1).41 Due to the avoidance of the first-pass metabolism, transdermal selegiline has much greater bioavailability than an oral formulation and can achieve an antidepressant effect with a lower dosage.42 Dietary restrictions are not necessary with the lowest dosage of transdermal selegiline (6 mg/24 h), improving the likelihood of adherence; however, a low-tyramine diet must still be followed with higher doses due to a lack of safety data. Precautions against drug interactions must also be taken with the transdermal selegiline at all doses, as with other MAOIs.
Not only does the transdermal formulation of selegiline lessen the risk for serious potential food interactions that accompanies other irreversible MAOIs, but its side effect profile is superior to that of other types of agents that are used in patients with treatment-resistant depression. Except for application site reactions, transdermal selegiline has a tolerability profile similar to that of placebo.16 Therefore, patients who have been nonadherent to their earlier antidepressants due to intolerable side effects, including weight gain43 and sexual dysfunction,44 might benefit from the use of transdermal selegiline.
Treatment rates for depression have increased dramatically in recent years, but treatment resistance is common and remission and response rates remain low. Nonadherence to antidepressants can adversely affect treatment outcomes and contribute to the economic burden of depression through higher utilization of health care services and greater loss of productivity. Multifaceted interventions employing a variety of educational, behavioral, affective, and provider-targeted components can increase adherence rates. To increase the likelihood of adherence, persistence, and stability of treatment, tolerability and efficacy should be considered when choosing among antidepressants. For some patients with resistant depression or problems with adherence to oral medication, a transdermal MAOI formulation may be a suitable option.
Going forward, additional research can help to illuminate the position of transdermal selegiline in depression treatment algorithms. For instance, should treatment guidelines move the formulation up in the treatment process, and, if so, under what circumstances? If a patient has benefited from an oral MAOI but has also experienced adverse side effects, is there an equivalency between the amount of oral agent needed to attain symptomatic relief and the dosages of the selegiline patch? Additionally, what is the economic profile of transdermal selegiline compared with oral agents? Does the patch enhance adherence, and does that translate to a reduced overall cost profile? And, finally, what is the best way to educate practitioners about classic MAOIs and the newer MAOI formulations, so that prescribers feel more comfortable in prescribing them to patients who might benefit from them? For a more in-depth look at these questions, see "Discussion: A Fresh Look at Monoamine Oxidase Inhibitors for Depression" in this Supplement.45
Answering these questions will help to guide clinicians and, particularly, primary care physicians, who now provide the majority of outpatient treatment for depression. The advent of SSRIs and other newer antidepressants that were easier to administer than earlier treatments helped prescribers to feel more comfortable prescribing psychotropic medications to their patients with depression.46 The transdermal formulation of selegiline now provides an easier-to-manage MAOI option and offers physicians another alternative for patients with atypical or treatment-resistant depression.
Drug names: lidocaine (Lidoderm and others), rivastigmine (Exelon and others), rotigotine (Neupro), selegiline transdermal system (EMSAM).
Disclosure of off-label usage: Dr Cohen has determined that, to the best of his knowledge, no investigational information about pharmaceutical agents that is outside US Food and Drug Administration-approved labeling has been presented in this activity.
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