Wednesday, February 17, 2016

Pain of Blogging Leaves Me Depressed

Good thing they have a pill for that:

"Could a drug that tamps down inflammation lift the fog of depression?" by Asher Mullard, January 28, 2016

One of the world’s largest drug makers is testing a radical new approach to treating depression — by dialing down inflammation in the body, rather than tinkering with chemicals in the brain.

It's from the elbows down, doc.

If it works, it’s likely to be expensive, have serious side effects, and help only a subset of patients. But it could also open the door to a whole new field of drug development for other psychiatric conditions, including bipolar disorder, anxiety disorders, and schizophrenia.

The global trial is run by Johnson & Johnson.

Didn't they just announce a bunch of job cuts?

Depression was long thought of as a simple imbalance of brain chemicals, and nearly all antidepressants used today work by tweaking levels of these neurotransmitters. Each year, more than 35 million Americans turn to those drugs. But 1 in 3 finds no relief.

Given that low response rate, especially in people with mild and moderate forms of depression, many psychiatrists have begun to reconsider the underlying drivers of the disease.

One possible culprit: inflammation, a process that occurs when the immune system shifts into high gear. Inflammation normally helps keep bacteria and viruses at bay. In the absence of an infection, however, it can also cause tissue damage, hay fever, autoimmune disease — and mental illness.

A long list of studies now support the idea of depression as an inflammatory disorder.

And here I thought it was just the obfuscated, distorted, and divisive slop I was reading each morning.

Depressed patients often have high levels of inflammatory markers in their blood, for example. And a pro-inflammatory drug that was formerly used to treat hepatitis C caused depression in up to 40 percent of people who took it.

I'm glad I say no to drugs because I'm nothing but an old arthritic fart these days.

“As recently as 2000, this was considered a fringe area of science, viewed with considerable skepticism,” said Dr. Wayne Drevets, a psychiatrist who leads mood disease research at J&J. “It is now mainstream thinking in biological psychiatry.”

Related: Putting This Blog in the CRISPR

J&J started enrolling patients with major depressive disorder last summer at sites in Russia, Poland, Canada, and the United States. The company is testing an experimental drug called sirukumab, which blocks a key inflammatory protein called interleukin 6.

The company didn’t initially set out to create the drug for people with depression. Doctors were running a trial of sirukumab in patients with rheumatoid arthritis, a chronic inflammatory disorder of the joints, when they came across an encouraging finding. After sifting through the data, they noticed that many patients’ moods improved even when their disease symptoms stayed the same.

This intrigued the higher-ups at J&J, and the company decided to put its drug to a proper antidepressant test, launching a 142-person, Phase 2 trial that should wrap up by the end of this year. (At the same time, sirukumab remains in development for rheumatoid arthritis and an inflammatory disease of the arteries.)

Even with best-case results, however, anti-inflammatories are not set to be a cure-all for depression. “This treatment will end up being reserved for patients who aren’t getting better with other things,” Drevets said.

Good, because I kind of stopped taking them. I don't like to take any pharmaceutical.

In part this is because the drug puts the brakes on the immune response, and so could increase the risk of infections, a side effect that might make it a tough sell for some patients. 

Ya' think?

I'll have to simply live with the pain considering the alternatives.

Sirukumab is also an antibody drug — a type of “biologic” therapy that typically commands a high price tag — and doctors may be loath to prescribe a costly new antidepressant over cheap, generic alternatives.

Yeah, biologic therapeutics is what they are calling this foray into a Brave New World.

What’s more, anti-inflammatories are only likely to act as mood modulators in patients with higher than usual levels of inflammation.

J&J is using a biomarker called C-reactive protein to identify these patients. About half of all people with depression who do not respond to conventional therapies have high levels of this protein, according to Dr. Andrew Miller, a psychiatrist at Emory University, who is not involved in the sirukumab trial but has collaborated with J&J in the past.

There’s more at stake with the sirukumab study than just one drug, though. The pharmaceutical industry has been plagued by repeated failures to move beyond conventional antidepressants, and rival drug companies interested in psychiatric disease will be watching the sirukumab trial closely.

You know, it almost seems like keeping you depressed is good bu$ine$$. 

Then I think of the kind of world the corporate-controlled con$umer-oriented media presents us and the unsatisfied attitude it breeds in the consumer.

Positive results for J&J, said Miller, “could see [other] companies try to get back in on the act.”


My addiction is this:

“The biggest thing we trade in is hope. Our biggest enemy is hopelessness. That’s why I think language matters a lot.” 

That's why I'm here every day asking questions, despite the pain.

Too bad the Globe's ‘music’ is so $our to the ear.

Maurice White, 74; founder of Earth, Wind & Fire
Jefferson Airplane co-founder Paul Kantner dies at age 74
Paul Kantner, 74; Jefferson Airplane cofounder, catalyst
Signe Anderson, 74; original Jefferson Airplane singer

They sounded much better before they left.

Doctors only ask patients about mental health problems half the time

No comment. 

If only the words could be telepathically typed onto the screen, 'eh?

Designing for a science fiction future in which people connect computers to their brains and experience the data of cyberspace as if it had physical form

They insure us that nothing can go wrong because the brain, it turns out, may be the ultimate Big Data generator.

What is next, the computer talking to you?

"Computers that sound human move near reality" by John Markoff New York Times   February 15, 2016

NEW YORK — When computers speak, how human should they sound?

This was a question that a team of six IBM linguists, engineers, and marketers faced in 2009, when they began designing a function that turned text into speech for Watson, the company’s “Jeopardy!”-playing artificial intelligence program.

Eighteen months later, a carefully crafted voice — sounding not quite human but also not quite like HAL 9000 from the movie “2001: A Space Odyssey” — expressed Watson’s synthetic character in a highly publicized match in which the program defeated two of the best human “Jeopardy!” players.

The challenge of creating a computer “personality” is now one that a growing number of software designers are grappling with as computers become portable and users with busy hands and eyes increasingly use voice interaction.

Machines are listening, understanding, and speaking, and not just computers and smartphones. Voices have been added to a wide range of everyday objects like cars and toys, as well as household information “appliances” like the home-companion robots Pepper and Jibo, and Alexa, the voice of the Amazon Echo speaker device.

The Amazon echoes back to the NSA, you know. 

No jibo as we move forward into a Terminator-type future.

A new design science is emerging in the pursuit of building what are called “conversational agents,” software programs that understand natural language and speech and can respond to human voice commands.

However, the creation of such systems, led by researchers in a field known as human-computer interaction design, is still as much an art as it is a science.

It is not yet possible to create a computerized voice that is indistinguishable from a human one for anything longer than short phrases that might be used for weather forecasts or communicating driving directions.

Actually, I thought it was but more on that below(?).

Most software designers acknowledge that they are still faced with crossing the “uncanny valley,” in which voices that are almost human-sounding are actually disturbing or jarring.

The phrase was coined by the Japanese roboticist Masahiro Mori in 1970. He observed that as graphical animations became more humanlike, there was a point at which they would become creepy and weird before improving to become indistinguishable from videos of humans. The same is true for speech.

“Jarring is the way I would put it,” said Brian Langner, senior speech scientist at ToyTalk, a technology firm in San Francisco that creates digital speech for things like the Barbie doll.

He likes playing with Barbie dolls? 

What's next, a talking cat?

Beyond correct pronunciation, there is the even larger challenge of correctly placing human qualities like inflection and emotion into speech. Linguists call this “prosody,” the ability to add correct stress, intonation, or sentiment to spoken language.

Today, even with all the progress, it is not possible to completely represent rich emotions in human speech via artificial intelligence. The first experimental-research results — gained from employing machine-learning algorithms and huge databases of human emotions embedded in speech — are just becoming available to speech scientists.

So they say.

Synthesized speech is created in a variety of ways. The highest-quality techniques for natural-sounding speech begin with a human voice that is used to generate a database of parts and even subparts of speech spoken in many different ways. A human voice actor may spend from 10 hours to hundreds of hours, if not more, recording for each database.

So they can copy and paste your speech to make it seem like you are saying something. They are admitting it. If they have recordings of your voice, they can splice together sentences.

The importance and difficulty of adding an intangible emotional quality can be seen in the 2013 science fiction movie “Her,” in which a lonely office worker played by Joaquin Phoenix falls in love with Samantha, the synthetic voice of an advanced computer operating system.

That voice was ultimately portrayed by Scarlett Johansson, after the film’s director Spike Jonze decided the voice of the original actress did not convey the romantic relationship between human and machine that he was trying to portray.

I haven't seen the film, and likely will not.

The roots of modern speech synthesis technology lie in the early work of the Scottish computer scientist Alan Black, who is now a professor at the Language Technologies Institute at Carnegie Mellon University.

Even though major progress has been made, speech synthesis systems do not yet achieve humanlike perfection, Black concedes. “The problem is we don’t have good controls over how we say to these synthesizers, ‘Say this with feeling,’ ” he said.

For those like the developers at ToyTalk who design entertainment characters, errors may not be fatal, since the goal is to entertain or even to make their audience laugh. However, for programs that are intended to collaborate with humans in commercial situations or to become companions, the challenges are more subtle.

These designers often say they do not want to try to fool the humans that the machines are communicating with, but they still want to create a humanlike relationship between the user and the machine.

IBM, for example, recently ran a television ad featuring a conversation between the influential singer-songwriter Bob Dylan and the Watson program in which Dylan abruptly leaves the stage when the program tries to sing. Watson, as it happens, is a terrible singer.

The advertisement does a good job of expressing IBM’s goal of conveying a not-quite-human savant. They wanted a voice that was not too humanlike and by extension not creepy.

Dylan sold out big time.

“Jeopardy!” was a particularly challenging speech synthesis problem for IBM’s researchers because although the answers were short, there were many mispronunciation pitfalls.

“The error rate, in just correctly pronouncing a word, was our biggest problem,” said Andy Aaron, a researcher in the Cognitive Environments Laboratory at IBM Research.

Several members of the team spent more than a year creating a giant database of correct pronunciations to cut the errors to as close to zero as possible. Phrases like brut Champagne, carpe diem, and sotto voce presented potential minefields of errors, making it impossible to follow pronunciation guidelines blindly.

The researchers interviewed 25 voice actors, looking for a particular human sound from which to build the Watson voice. Narrowing it down to the voice they liked best, they then played with it in various ways, at one point even frequency-shifting it so that it sounded like a child.

“This type of persona was strongly rejected by just about everyone,” said Michael Picheny, a senior manager at the Watson Multimodal Lab for IBM Research. “We didn’t want the voice to sound hyper-enthusiastic.”

The researchers looked for a machine voice that was slow, steady and most importantly “pleasant.” And in the end, they, acting more as artists than engineers, fine-tuned the program. The voice they arrived at is clearly a computer, but it sounds optimistic, even a bit peppy.

“A good computer-machine interface is a piece of art and should be treated as such,” Picheny said.

I'm sorry, I stopped listening. 

Whatcha say?

As speech technology continues to improve, there will be new, compelling and possibly perturbing applications.

Imperson, a software firm based in Israel that develops conversational characters for entertainment, is now considering going into politics. Imperson’s idea is that during a campaign, a politician would be able to deploy an avatar on a social media platform that could engage voters. A plausible-sounding Ted Cruz or Donald Trump could articulate the candidate’s positions on any possible subject. 

As if that realm of the this world wasn't filled with enough imitations, impersonators, and liars already. 

And now some Israeli company will actually be putting words into their mouth. 

Who needs AIPAC anymore, huh?

“The audience wants to have an interactive conversation with a candidate,” said Eyal Pfeifel, co-founder and chief technology officer of Imperson. “People will understand, and there will be no uncanny-valley problem.”

The web version just wouldn't stop talking!


Such a thing might scare me to death

So who was the father of all this anyway?

Marvin Minsky, 88; MIT professor helped found field of artificial intelligence

"Born in New York City, Dr. Minsky grew up in Manhattan and the Bronx. He was the middle child and only son of Dr. Henry Minsky, an eye surgeon, and the former Fannie Reiser, a Jewish activist. He attended the progressive Fieldston School and then went to the Bronx High School of Science, until his parents sent him to Phillips Academy in Andover his senior year to increase his chances of getting into a top university. His 1960 paper “Steps Toward Artificial Intelligence” is considered a seminal work in shaping the field."

In Minsky’s wake, machines get smarter

Others called home:

"Richard Libertini, a character actor best known for a regular role as the Godfather on the ABC satire “Soap,” died Jan. 7."

Abe Vigoda, sad-eyed character actor; at 94

Mary Fiumara, 88; mother from Prince Spaghetti commercial

This was my calling, readers.