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Macbeth takes quite the literal role of a "backstabber" as he murders Duncan, the King he is supposed to respect and love. But also the King who honored him personally.

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This is the sight Macduff sees. This is the horror he expresses when he says "confusion now hath made his masterpiece."

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Sorrow of God and Angels from Duncan's death

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Sorrow of God and Angels from Duncan's death

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Animals go wild, the Gods and angels are disturbed by the King's horrible death.

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Macbeth and Lady Macbeth realize what they have done. Lady Macbeth keeps herself composed as Macbeth fears what he has done.

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Macbeth kills Duncan out of pure greed to be king, the beginning of evil deeds.

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This quote signifies a reaction of horror.
To Anyone, it's an expression to show deep confusion.
To Shakespeare, it's something said that's often accompanied with horrific news.
For me, it signifies a tragic loss from a person who cannot express his/her true emotions from the horror yet.

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1. The murder of nine people in a church- this connects with Macduff's following lines "Most sacrilegious murder hath broke ope The Lord’s anointed temple," because of their connections with God. http://www.npr.org/sections/thetwo-way/2016/11/06/500903477/jury-selection-set-to-begin-in-south-carolina-church-shooting-trial
2. 300 year old royal murder mystery- this connects with the fact that Duncan was also a royal king and murdered mysteriously. It connects with Macduff's lines "O Banquo, Banquo, Our royal master’s murdered!"  because of the shock of a royal death (and by murder).
http://news.nationalgeographic.com/2016/11/german-skeleton-murder-mystery-king-george/
3. Murders of more than 30 women in Turkey- though Duncan was obviously not a woman, he was a humble, kind king. The women (and even some children) killed in Turkey were most likely also made to act this way, making the horrors horrific. This connects to Macduff's lines "O gentle lady,

'Tis not for you to hear what I can speak: The repetition, in a woman’s ear,

Would murder as it fell." because it shows the delicacy of a woman.
https://pjmedia.com/blog/murder-of-women-in-turkey-skyrocketing-as-country-islamicizes/

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Song This Quote Relates To: Jack's Lament

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Song This Quote Relates To: Jack's Lament

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"There are few who deny, at what I do I am the best
For my talents are renowned far and wide
When it comes to surprises in the moonlit night
I excel without ever even trying
With the slightest little effort of my ghostlike charms
I have seen grown men give out a shriek
With a wave of my hand and a well-placed moan
I have swept the very bravest off their feet"
-The beginning of this song reflects how Macbeth grows in the first acts. Macbeth is also the best at what he does, few deny it. His talents are renowned "far and wide" by the King and by all others. "I have seen grown men give out a shriek" would represent Macbeth once he has committed all of his murders.

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First time: My friends and I were talking about Macbeth and how the story unfolds, I added "Yeah, confusion now hath made his masterpiece." Their response was "who said that?"
Second time: I was talking to my boyfriend about finally watching The Nightmare Before Christmas for the first time, and he asked how I liked it. I told him it was good, but when Jack (the pumpkin king) was caught between Christmas and Halloween, "confusion now hath made his masterpiece", his reaction was "That's not even the best quote!" Of course it wasn't, it was from Macbeth, not the movie.
Third time: I was having a hard time bringing this up into conversation, so I asked my friend's mom to tell my friend something confusing. When my friend looked oddly at her mom, I said "aha, confusion now hath made his masterpiece!" She looked even more confused.

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"CONFUSION NOW HATH MADE HIS MASTERPIECE" Act 2, Scene 3, Line 40

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"CONFUSION NOW HATH MADE HIS MASTERPIECE" Act 2, Scene 3, Line 40

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My initial reaction while reading was to jump over it, but now as I look closer, I see that it means something horrific has happened. In this case, Duncan's murder.