Home in the Clouds

Deconstructing a Full Prescribing Information: Part X Wednesday 5/23/12

The greatest concern of all.

Studies Pertinent To Safety Concerns For Sedative/Hypnotic Drugs

Cognitive, Memory, and Sedative, and Psychomotor Effects

In two double-blind, placebo-controlled, single-dose cross-over studies of 12 patients each (one study in patients with insomnia; one with normal volunteers), the effects of LUNESTA 2 and 3 mg were assessed on 20 measures of cognitive function and memory at 9.5 and 12 hours after a nighttime dose.

A double-blind study is a study in which neither the patients or the doctors know that the patients are taking LUNESTA.  This is done to eliminate subjectivity and bias.  Placebo is a useless medication – it has no effect.  Placebo serves as the “control” of the experiment – the bottom of the scale to compare Lunesta’s effectiveness to.

Comparison of Double-Blind Placebo-Control Food Dye Challenge Studies (Photo credit: Wikipedia)

Although results suggested that patients receiving LUNESTA 3 mg performed more poorly than patients receiving placebo on a very small number of these measures at 9.5 hours post-dose, no consistent patterns of abnormalities was seen.

Essentially, some of the patients “performed more poorly” after 9.5 hours with Lunesta over placebo.  I’m not sure what “performed more poorly” quite means, though with the usual “don’t operate heavy machinery” warning, I guess I can suppose it’s something like that.

Up next: memory impairment!  Don’t worry, it’s not really that bad.  Was it?  I don’t remember.  *rimshot*

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Related articles

• Embracing the Placebo Effect of Antidepressants. (jailmedicine.com)
• Pharmacologic Management of Delirium in the Intensive Care Unit; A New Review (jajsamos.wordpress.com)
• Okay, these aren’t really related.  But they sound cool.

Minecraft (Part I): Introduction Wednesday 5/9/12

If you browse the Internet at all, you’ve probably heard of Minecraft.  It has exploded into massive popularity ever since it was introduced in mid-2009.

Minecraft Logo

Minecraft is a PC game, made of a mix of creative sandbox, first-person combat, and RPG elements.  It has been widely noted for its… simple… graphical style with most items in the game having no greater resolution than the icons in your taskbar.

A Screenshot of Minecraft ‘classic’ (Photo credit: Wikipedia)

Here’s how it works: after you buy the game, you are unceremoniously dropped in a massive, randomly-generated world. This world is comprised of large blocks, each one cubic meter in size.  The world looks like many places in nature, such as lush forests, vast deserts and deep oceans.

But you have to move quickly.  The sun quickly rises, starting the 10-minute day.  When the sun sets and night falls, the monsters come out and try to kill you.  You need to build or find a shelter before the moon rises.After you establish a home, you can dig down into the ground and discover large cave system scattered with ores such as coal, iron, even diamond.  You need to be even more careful, as the dark caves are a favorite hiding place for the monsters.  Additionally, large lakes of boiling lava are found deep, and will burn you and your stuff to ashes if you fall in.

As you expand your resources, become better at combat, you can start thriving instead of just surviving.  The unique thing about Minecraft is how creative its players can be.  You are offered a wide palette of building materials, such as wood, stones, bricks, even wool and snow.  You can use these to build houses, elaborate underground bases, stone castles, water rides, skyscrapers, even entire cities.  You can even play with other people on dedicated servers.

A redstone circuit.

Another popular but highly advanced aspect is the usage of redstone.  Redstone is a fictional ore that behaves much like electrical circuits in the real world.  Many processes can be automated through redstone circuitry, and complex devices can be made that do incredible things.  It can be also used for simple things such as opening a door as you approach it.

Minecraft is an indie (independent) game developed by Mojang out of Sweden.  It was first started by Markus “Notch” Persson as a small hobby.  It has since grown to over 5.8 million users and is highly popular.It’s not a free game, but it provides many hours of fun, and is highly expandable, with third-party custom “adventure” maps and many modifications that add new features and items.

Deconstructing a Full Prescribing Information – Part IX Tuesday 2/21/12

The studies continue!

In addition, a 6-period crossover PSG study evaluating eszopiclone doses of 1 to 3 mg, each given over a 2-day period, demonstrated effectiveness of all does on LPS, and of 3 mg on WASO.  In this trial, the response was dose-related.

A polysomnograph study is a sleep study that monitors a person while they sleep.  Things such as heart rate, brain activity, and eye movement are monitored.  Once again, LPS refers to lipopolysaccharide (probably), and WASO is wake-after-sleep-onset; that is, waking up in the middle of the night.

Image via Wikipedia

Elderly

Elderly subjects (ages 65-86) with chronic insomnia were evaluated in two double-blind, parallel-group studies, of 2 weeks duration.  One study (n = 231) compared the effects of LUNESTA with placebo on subjective outcome measures, and the other (n = 292) on objective and subjective outcome measures.  The first study compared 1 mg and 2 mg of LUNESTA with placebo, while the second study compared 2 mg of LUNESTA with placebo.

Remember that (n = 231) and (n = 292) indicated the size of the groups tested.

All doses were superior to placebo on measures of sleep latency.  In studies, 2 mg of LUNESTA was superior to placebo on measures of sleep maintenance.

It works in the elderly, basically.

Up next is studies concerning safety.  Buckets o’ fun!

Image via Wikipedia

Release: TimeView Sunday 2/19/12

TimeView is a novelty clock program that displays the time in many different formats, including hexadecimal, binary, and even Roman numerals!  This is the release page for version 1.0.

System Requirements

• A computer with the .Net Framework 4.0 installed*

And that’s about it – TimeView is a lightweight app.

Installation

Installation is not required – just extract the files and run.

Features

The features of TimeView are split into four tabs:

Clock

Clock

This tab shows the time and date formatted in decimal, hexadecimal, and binary number bases.  If you need help reading the formats, just click the ? button beside the times.

Progress Tab

Progress

This tab displays how far into each unit of time the day is, formatted in progress bars.  They’ll be blocks in Windows XP, though.  The numbers can also be formatted in decimal, hexadecimal, or binary.

Color Tab

Color

This tab displays the color of the time, which is arrived at by taking the RGB color of the hexadecimal time, which is conveniently six hex digits.  It’ll update per second, and the current RGB color values are displayed at the top.

Roman Tab

Roman

This tab displays the time and date formatted into Roman numerals.  As it’s our time format, rather than the Roman’s, the formatting is a bit odd.

Download

This software is licensed under the GNU General Public License.

Download (v1.0 for Windows)

Source Code (for Visual C# 2010 Express Edition)

A Plot Summary of Portal 2 (originally supposed to be a review) Friday 2/17/12

Warning: massive spoilers ahead.

Start thinking with portals.

Portal 2 is a 2011 video game released by Valve Software.  It’s essentially a mix of a first-person shooter and a puzzle game.  You play as Chell, trapped inside the maniacal Aperture Science Enrichment Center – and you’re the only human still alive in there.  The thing running the facility is the insane Genetic Lifeform and Disk Operating System  – GLaDOS .  Or at least she was.

In the first Portal, you worked through a series of testing chambers.  You were testing Aperture’s new invention – the Aperture Science

Image via Wikipedia

Handheld Portal Device – a gun that can shoot two interconnected portals on walls, ceilings, and floors.

The concept of portals is simple – walk through one, come out the other.  You can even see through them.  Momentum is also preserved, so if you fall into a floor portal from a great height, you’ll come flying out of a wall portal at the same speed.

GLaDOS’s personality in Portal is strange – during the testing, she presents herself as a simple computer, advertising Aperture’s products and occasionally glitching out.  She also demonstrates Aperture’s extreme carelessness surrounding safety:

Please note that we have added a consequence for failure.  Any contact with the chamber floor will result in an “unsatisfactory” mark on your official testing record, followed by death.  Good luck.

After clawing your way through 20 tests, she tells you that you’ll get cake – instead, you get a burning fire pit at the end.  After escaping a very warm death, you crawl through the bowels of Aperture Science until you reach GLaDOS’s chamber.  She didn’t expect you to try to escape, so she did away with her cold computerized demeanor and became more emotionally charged the closer you got to her.  Using  portals and her own rocket turret, you dislodge the intelligence cores regulating her behavior, then proceed to unceremoniously dump them into an incinerator as she gets progressively more unhinged.  While she’s filling the chamber with neurotoxin.

As you burn up her last core, she explodes and the facility pulls you out of itself via some sort of vacuum implosion.  You lie on the Aperture front walk before the burning hunk of GLaDOS.  And then a robot pulls you back into the facility.

And that’s Portal 1.

The Actual Review plot summary

You wake up fifty days later in a cruddy motel room.  Wait, it’s cruddy motel room slash hibernation chamber inside Aperture.  Another computer – this one just a recording – puts you through some basic cognitive exercises (which also teach the players about the basic controls).  You return to bed – and wake up an incredibly long time later.  The room has decayed, lights have failed, and the entire place is utterly overgrown.  The computer tells you it’s been 999… 9999, and breaks.

A bumbling British-accented intelligence core called Wheatley comes to wake you up.  He informs you of the situation – without GLaDOS, the entire facility fell into a state of catastrophic disrepair and overgrowth, and the nuclear reactor is about to explode.  He takes your cruddy-motel-room-in-a-box for a bit of a ride with an old testing track as a destination.  He crashes and bangs into about half the facility, utterly tearing your box apart.

You enter the testing tracks to find the old portal gun.  The first five chambers are the same chambers from Portal, except they are decayed and overgrown.  You acquire the portal gun, learn about the basic testing elements, and escape with Wheatley toward the main breaker room.

Unfortunately for you, between here and there is Her Chamber with GLaDOS’s husk still lying inside.  The good news is that she’s still dead, and you make it to the breaker room untouched.  Wheatley has you plug him into the control panel to turn on the lights.  Being the moron that he is, he accidentally starts rising the platform, flipping a bunch of breakers along the way.  This has the side effect of resurrecting GLaDOS.

She is understandably unhappy when she sees you.  Rather than kill you, she just decides to kill Wheatley and drop you into the incinerator.  Luckily, the flames have died down somewhat.

You fall thousands of feet (you have long fall boots which nullify fall damage), land in the incinerator chamber, and make it to the dual portal gun (shoots both colors instead of one).  From there, you work backward through old Test Chamber 19, and enter GLaDOS’s series of tests.  But it’s not over yet.

Wheatley shows up in the testing series, having been reactivated by a bird, as he says.  In Test Chamber 21, he breaks you out halfway through, and you escape the area as GLaDOS tries to kill you several times in a row.  She even reveals the last test chamber – a death trap.  You eventually escape to manufacturing, where she doesn’t have as much control.  You make your way to Turret Manufacturing (turrets being immobile robots with guns, disabled by knocking over).  Here, you replace the good turret, used as a template, with a defective turret, so that all defective turrets will pass quality control.

From there, you proceed to the neurotoxin generator.  After imploding that, you are sucked into one of Aperture’ glass-walled tubes used to transport test objects.  It takes you and Wheatley right to Her Chamber, where she (tries) to kill you with turrets and (tries) to kill you with neurotoxin.

The computer gives you a chance to swap GLaDOS for Wheatley, which you accept.  GLaDOS is unceremoniously ripped off her old body, and Wheatley is put in charge of the entire facility.  He calls an escape lift for you to exit, but something happens to him.  Apparently, and core attached to her mainframe is addicted to testing, and becomes more violent and angry.  Wheatley loses his mind, and accuses you of being selfish – according to him, he was the only reason you made it to this escape elevator.  GLaDOS, lying immobile on the floor, comes to your aid, which infuriates Wheatley.  He pulls her head back into the floor, and puts her inside a potato battery.

It is now when GLaDOS (now known as POTaTOS) realizes who Wheatley is – he is an Intelligence Dampening Core, made by Aperture’s scientists to regulate her behavior.  He gave her a constant stream of terrible ideas, fogging her mind.  Unfortunately, she proceeds to call him a moron.  Which is his Berserk Button.  He punches the elevator with the potato hard enough that the glass cracks, and then throws the potato in the elevator.  He proceeds to pound the elevator down the shaft it came up, at least until the bottom gives out.  And then you fall. And fall.  And fall.

And fall.

You fall about three miles, with POTaTOS falling with you.  During this minute-and-a-half drop, she tells you more about Wheatley (my favorite quote is “He’s the product of the greatest minds of a generation working together with the express purpose of creating the dumbest moron who ever lived.”)  Wheatley is also programmed to automatically make the worst possible decisions (apparently without noticing it).

You eventually hit the bottom, and even though you have long fall boots on, you still pass out from the impact.  When you awaken, you first see POTaTOS being carried off by a bird.

At the bottom of this precipitous drop is the old facilities of Aperture Science Innovators.  Built in an old salt mine in Michigan, the facility spans millions of square feet.  A strange, bright blue fog lies around the “ceiling” of this giant cave, giving faint illumination to the dozens of thick towers made of solid stone, presumably to support the facility’s wall.

Time has taken its toll on the 999999-plus-old facility, but not as much as the more modern Aperture 15,000 feet above.  While structural decay is significant, nature did not have a chance to encroach as it did in New Aperture.  Still, there are burning piles of metallic rubble, rusting metal columns lying abandoned on the ground, as thin layers of goo here and there.

You portal your way around to the seal.  It’s been said by Valve to be “the largest door in video gaming”.  Opening it involves pressing two buttons on opposite sides of the chamberlock within three seconds of each other – with portals, this task is no hard feat.  The lights turn on, the door comes to life, and fifty tons of metal slowly opens.

Behind it?  A solid wall, with a man-sized door in the corner.  Next to a couple of chairs.

Beyond the seal is the 1950’s era Aperture Science Innovators.  Prerecorded voices of Aperture’s CEO, Cave Johnson, play as you walk into the building.  You’re in the testing section – here they tested an old version of the portal gun – with a backpack device to boot, along with three kinds of gels.

The first gel is called repulsion gel – it’s blue, and when you jump on it, you bounce around.  The second is propulsion gel – you run much faster on it than you normally do.  The third is conversion gel – it’s white, and it coats surfaces so you can now shoot portals on them.

In 1950’s Aperture, you’ll be testing repulsion gel first.  You pass through some introductory tests, and then get into the harder ones.  Some of the catwalks have collapsed, so you’ll need to do advanced flinging to get from place to place.

While you test, Cave Johnson demonstrates his utter indifference toward any semblance of safety.  Feet-deep pools of toxic acid lie in many areas with no railings to protect anyone, drops and falls dominate many test chambers, the test chambers have asbestos walls, and the experiments he talks about include test subjects unknowingly getting microchips embedded in their skulls.  Oh, and tumors.  Which you get from folding chairs in the lobby.  A few vitrified (more succinctly, glass-i-fied) doors play messages when you play them, such as Cave talking about how test subjects were being shot with lasers that turn blood into gasoline.

You finish the repulsion gel tests, and you proceed to the next area of Aperture: 1970’s Aperture were Propulsion Gel was tested.  By this point, Aperture had fallen on harder times, and test subjects came from bums off the street, who were promised $60 for testing.  Safety is still the number ten-trillionth concern on Aperture’s list, with pools of acid still prevalent.

In the Control Room, you find a fallen vegetable.  POTaTOS is in a bird nest on a desk, with the bird pecking at her.  As you shoo the bird off, POTaTOS tells you that you have to team up if there’s any chance of survival.  She seems nicer now that she’s no longer in power (or, more importantly, not attached to her insanity-inducing mainframe).  You stab her with one of the “handles” of your portal gun to pick her up.

Being in a potato battery is a boondoggle for the AI; she has 1.1 volts (well, 1.15 volts being attached to the portal gun) to work with, meaning she has a tendency to reboot if she gets too emotional.

As you start the Propulsion Gel tests, a Cave Johnson message plays, and he’s asking his assistant Caroline about the $60 vouchers.  POTaTOS answers when Caroline does, greatly surprising the potato.  She knows she’s heard Cave’s voice before, but couldn’t think where.

As you proceed through the Propulsion Gel tests, it dawns on her a bit.  You see, Intelligence (or Personality) Cores got their personality from people who were brain-dumped into a core.  POTaTOS then realizes who she actually is.

You complete the 1970’s tests, and exit into the third and final branch of Old Aperture – 1980’s Aperture.  By this time, Aperture was utterly broke, but Cave didn’t care – he ordered $7,000,000 of moon rocks and ground them up into a gel – Conversion Gel.  As a gel, it’s somewhat safe, but as a dust, it’s deadly poison – which is what happened to Cave.

He informs you, coughing while doing so, that Aperture had switched to using their own employees and their children for testing.  Testing quality went up, but employee retention dropped, so Aperture moved away from human testing altogether.  He then laments on his fatal condition, but he has a plan:  Invent artificial intelligence so he can live in a computer.  He then ordered that, if he were to die before the system was ready, his assistant Caroline was to be uploaded in his placed.

You run the final tests, with Conversion Gel, and when you finish it, Cave gives a very… famous… rant about lemons.  And fire.

You’re almost there.  The last challenge you have to pass is a series of “tests” caused by the decaying environment destroying the catwalks.

More about Caroline.  She resisted into being stuffed into a computer, but the Aperture employees wouldn’t have any of it.  She was first enabled on Bring Your Daughter To Work Day, and she was very confused and very, very angry.  Oh, and she was in charge of the entire facility.  Including the neurotoxin.  Guess what happened next.

You make your way to the final room – the fourth pumping station.  You activate the enormous door on the ceiling, and three pipes descend from New Aperture to old, enabling the gels in the higher facility.  An elevator of sorts, descends from the ceiling and pulls you into the gap between new and old.  It’s a giant dark room with lots of huge springs supposedly supporting the weight of the Enrichment Center.  You walk up the stairs and into the modern chamberlock, leading you back up.

During your absence, Wheatley made a few changes to the facility.  He makes a new cube called Frankenturrets – two turrets smashed into a box – which is slightly sentient and clearly in great pain.  They also use their legs to hop around, and Wheatley’s new obsession with testing results in a couple tests of his own design, the first having a bunch of these cubes trying to jump on a button.

You enter into this “test chamber” and solve the test, which notifies Wheatley.  He appears on the flat-panel monitor and GLaDOS attempts to defeat him with a paradox.  To a computer, a paradox would freeze it as it devotes all its processing power to trying to solve the unsolvable.  Unfortunately, Wheatley is not so smart.  The paradox doesn’t even faze him – although the Frankenturrets are now sparking.

Wheatley expresses gratefulness that you’re back.  The body he’s on gives intelligence cores a fundamental addiction to testing.  He tried it with the Frankenturrets, but now he has the best test subject ever.  He sends you on his testing track.

His first (and only) test is one of the simplest puzzles ever – press a button to activate a cube dropper situated right over the exit button.  Cube drops, door’s opened and you leave.  When a test is solved, the core gets a great emotional release.  Because building tests is so hard for him, Wheatley has you solve the same test again, but it has no effect.

All the remaining tests are those of GLaDOS’s construction, which makes them much more dangerous.  He makes vague hints about a surprise he’s found, and implies that he wishes to kill you.  Meanwhile, he maintains exactly none of the safeguards preventing the nuclear reactor from exploding.

You work through about nine or so tests, and then you enter the final one, which looks simple – a Frankenturret is bouncing on a catapult in the middle of the room, and you just jump on another catapult to grab it.  That is, until said catapult launches you sideways.

It launches you out of the test chamber and toward a lone platform situated above the void.  Another Wheatley monitor is before you, along with about twenty giant spiked plates ready to crush you to death.  Using quick thinking, you escape, and make your way through the upper part of the Enrichment Center toward his lair.  Along the way, he tries several death traps, all of which are too obvious to fall for, but can pose some challenge.

As you escape the last death trap, you come to a room with a pile of dead and defective intelligence cores.  POTaTOS comes up with a plan to corrupt Wheatley and instantiate another core transfer.  You enter His Lair, and he anticipated your move, setting up a four-part plan partially based on your strategy used to kill GLaDO a game ago.  He’s removed the portal surfaces, has a bomb launcher, and shields to protect himself from the bombs.  He forgot, however, about the tubes of gels running through the facility.

You get one of his bombs to explode the Conversion Gel pipe, spraying everything with white gel, and enabling portals.  The facility begins to fall apart, and POTaTOS presents you the first core – a babbling, space-obsessed one, to attach to Wheatley after stunning him with one of his own bombs.

The facility continues to deteriorate before your very eyes as Wheatley awakens.  He realizes your strategy but doesn’t refactor his; bombs are still his weapon of choice.  You stun him again, and POTaTOS gives you the second core – a very manly core named Rick the Adventure Sphere.  You attach this core the Wheatley.

Fires have started to spring up and the entire facility is about to blow a chunk out of Michigan.  Wheatley awakens again, still using bombs, and you stun him one last time.  POTaTOS presents you the third and final core – a core that presents outlandish “facts” such as how one in five children will be abducted by the Dutch.  You attach this core the Wheatley and the computer records full corruption, allowing another core transfer.  He wakes up, immobilized, and refuses the transfer, leading to another stalemate.  The wall behind the Stalemate Resolution Annex is lowered, and you portal in there, ready to push the button.

PART FIVE!  BOOBY-TRAP THE STALEMATE BUTTON!

Wheatley placed several hidden bombs in the Annex, detonating as you approach the button.  You are ejected out of the room, badly injured but still alive.  As you pick up the portal gun, a section of the ceiling caves in, revealing the full moon above.  You notice a portal on the floor beneath Wheatley, and a crazy idea forms in your head.

You shoot the moon.

About three seconds later, the portals connect and a massive rush of air pulls you into the portal, along with Wheatley.  You are hanging from Wheatley as the air rushes out around you, and the brave little potato retakes the facility and knocks Wheatley out with it.  She pulls you back in, and you collapse.

You wake up some time later, apparently recovered.  POTaTOS is GLaDOS once more, and she now realizes that you, the player, may not actually be bad after all.  She also learns another important thing – where Caroline lives in her brain.

Caroline deleted.

After deletion of Caroline, GLaDOS returns to her old self, but instead of killing you, she grudgingly lets you go.  You ascend through the facility until you reach a door, which opens to reveal four turrets aimed right at you.  But instead of shooting at you, they sing.

You exit the elevator into a large, quiet field, with a cloudy sky above you.  You turn around to see a shed behind you, the only evidence of Aperture Science on the surface.  However, the door reopens, and a badly scorched Companion Cube, the same one you incinerated back in the first game, flies out the door.

After the end credits, Wheatley and the Space Core are shown floating in space.  Wheatley now regrets his actions, with his only wish that he could apologize.

…

Okay, that took a while to write.  I originally wanted a review but got caught up in writing about the plot, so I’ll write up an actual review later.