Acid Bit

By Robert Webb

 Neuronetics had tried last year (Jan 2007) to get FDA approval for its transcranial magnetic stimulation (TMS) device, but failed spectacularly. Transcanial magnetic stimulation is a way of non-invasively stimulating the brain with electromagnetism. So what the heck happened with the trial? Neuronetics showed the results of a clinical trial of TMS for major depression to a board of FDA advisors.

The primary efficacy outcome in the clinical trial was the reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) symptom score after 6 weeks. Secondary outcomes included changes in the 17- and 24-item Hamilton Depression Rating Scale (HAMD) (pdf). In the trial, the mean decrease in the MADRS scores was about 5.6 points in the active TMS and around 3.2 points in the sham TMS. Unfortunately for neuronetics, the p-value at the six week mark was .058. A p-value less than .05 is usually that difference between sham and active TMS that is considered statistically significant.

Anything higher than a value of .05 means that the trial technically failed to reach statistical significance. Since the MADRS was the primary outcome measure and it had a p value over .05, this was the statistic that caused the FDA to recommend against approval for the TMS device. The FDA could not get over the fact that the mean score on the MADRS was technically not statistically significant over placebo in the mean change in depression scores for patients. Statisticians argued to the FDA that a p-value of .058 is clinically indistinguishable from a p-value of .05, but that wasn’t good enough for the board evaluating the TMS device.

Looking at the other statistics this specifc trial, the active TMS did reach statistical significance over sham when measured by the secondary outcome symptom scales (HAMD-17 and HAMD-24). So why is it that the TMS device did reach statistical significance on some measures but not others? Well, the MADRS, HAMD-17 and HAMD-24 (pdf) are 3 different scales with completely different rating items.

The TMS is activating a specific area of the brain (the left dorsolateral prefrontal cortex (LDPFC)). Left dorsolateral prefrontal dysfunction (LDPFC) is associated with pseudodepressive symptoms. These type of symptoms include apathy, indifference, anergia, poor concentration and psychomotor retardation. So what likely happened on the neuronetics trial is that specific ratings scales may load more or less heavily on LDPFC dysfunction. The MADRS may not have reached statistical significance because not enough items measured the pseudodepressed type of symptoms associated with LDPFC dysfunction.

This past november (2007), neuronetics had gotten results from a new trial. Surprisingly neuronetics again used the reduction in mean MADRS scores as the primary outcome measure but after 4 weeks instead of 6 weeks. For this new trial, active TMS does show statistically significant improvement over sham TMS with a p-value of .038. Unfortunately there is only a trend for more improvement evident at six weeks with a p-value of .052. The difference between active and sham just missed statistical significance at the six week mark. Both HAMD-17 and HAMD-24 had a reduction in mean scores that was statistically significant for the active treatment over sham (P=0.006 and P=0.012) at four weeks and at six weeks (P=0.005 and P=0.015).

So in this second trial, they at least got clinical efficacy on their primary measure. However that fact that the MADRS mean score didn’t distinguish itself from sham after six weeks is not so good. Will the FDA see past this fact and approve the device? It seems that it will be a close call, but I don’t have confidence that it will be approved. Neuronetics really messed up on both of these trials. If they had looked at the specific rating scale items, they probably could have predicted which rating scale to use as a primary outcome measure.

My guess is that there was a greater reduction in symptoms as measured by the HAMD rating scale because the items load more on LDPFC dysfunction than the MADRS scale. Not to mention that neuronetics used treatment resistant depressed patients in the trial. They are much less likely to respond to treatment than normal patients and make the end results of the trial look, well, depressing.

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It’s the End of the World As We Know It
By Patrick Omari

 Wednesday the 10th of September could be the last day in the history of the World, which wouldn’t be very convenient for those with travel plans at the weekend. What could cause the end of the world; a meteor strike? A mass tsunami? Or something man made? Something mechanical in the good name of ’science’ perhaps.

It could either be the end of the world or the start for a great period of scientific discovery in one of the most highly debated areas.

Fears are building as quick as protests can be mustered as scientists in Geneva at the European laboratory for particle physics (CERN) prepare to switch on its Large Hedron Collider. If the fears are held true we will all vanish into a black hole as the Earth and the solar system cease to exist. In this dimension at least.

While many are opposed to the experiment and fear it means the end, the physicists and scientists all agree that the collider is perfectly harmless and the chances of destroying the Earth through the experiment are infinitesimally small. CERN, who have been building the collider since 2003, have dismissed the risk of micro black holes and quasars being created by the experiment.

The idea is to gain a greater understanding of the Big Bang and the Universe as the Large Hedron Collider will explore the tiniest particles and come closer to re-enacting the Big Bang. The LHC will smash two beams of particles head-on at speeds close to the speed of light and scientists hope to see new particles in the debris of the collisions.

Proton beams - nuclei - will spin 11,000 times a second around the 17 -mile tunnel, nestled under 150-500 feet of earth on the French-Swiss border. Once a beam has been successfully fired counter-clockwise a clockwise test will follow before the scientists will aim the beams at each other so that the protons collide. Enough energy will be created to recreate conditions that existed one trillionth of a second after the Big Bang.

The energy will liberate thousands of quarks and gluons, normally imprisoned in the proton beams, which will then form the quark-gloun plasma. The plasma then cools and the quarks and gluons stick together forming protons and neutrons, the building blocks of matter and thus enabling scientists a greater understanding of the creation and makeup of matter.

The size of the tunnel and superconducting magnets give a hint but the size of this project is a monster in itself, black hole or no black hole. Researchers of 80 nationalities are involved and the price of the project sits at a cosmically large 5 billion pounds.

The first beams of protons will be fired to test the strength of the superconducting magnets, the largest on Earth, on Wednesday 10th and it will still be almost a month before the beams travelling in opposite directions are bought together in the collisions that so many are worried about.

So worried, in fact, that some protesters have filed suit in the U.S District Court in Hawai and in the European Court of Human Rights in an attempt to stop the project - citing that it incurs upon the basic human right to live.

It’s not just the potential calamity that could ensue that people are protesting over. The cost of the experiment has got a lot of people rattled especially considering the contributions from individual countries. With pressing issues such as climate change, many feel that the funding and research could be better spent.

While it may sound like the readings of an overly complicated science-fiction novel to some, the ideal cure for insomnia to others, a terrifying portent of doom to protesters or a huge waste of money and resources to those remaining nay-sayers, Wednesday’s experiment has certainly fired up a lot of debate before the machine has even been fired up.

Patrick is an expert travel researcher and writer currently researching Manchester Airport Parking, Manchester Airport Hotels and Airparks Gold Manchester

Is It Possible For Proteins To Form On Their Own?
By Russ Miller

 This is one of those questions that could cause a philosopher to suffocate under the sheer stress of pondering the incredible odds that would have to be overcome for such an event to happen. I will tell you how great those odds are later in this article.

Amino acids are the building blocks for proteins and must be in an exact order for a protein to operate. The scientific facts are that virtually all living things require all left-handed amino acids with all right-handed nucleotide sugars.

However, in a natural setting, the mix would be 50% right-handed and 50% left-handed amino acids and sugars. The probability of these coming together naturally is mathematically impossible.

For instance, proteins are the primary components of cells, and proteins are usually made from at least 22 different types of all left-handed amino acids. Just like letters of the alphabet that are used to make up a sentence, the proteins must also be in a specific order to have any meaning. This arrangement of letters, “To be or not to be, that is the question,” conveys meaning. However, the same letters randomly arranged, bTo oi oeh eo cv seno e utrn t ta qsn, have no meaning at all.

The odds of coming up with this line from Shakespeare, using randomly dropped Scrabble letters, are 1 in 2,810 trillion octillion! That is 2,810 with 39 zeros following it, which is another mathematical impossibility.

The same goes for amino acids being able to form proteins on their own in nature. Even the smallest known protein is made up of hundreds of left-handed amino acids. Mathematicians have calculated the odds of just one protein developing on its own in nature to be 10 to the 119th power: that’s 10 to the 119th power 22 times to arrive at the 22 proteins required to make one simple bacteria!

How big of a number is that? Well, double every molecule in the universe and you might get close.

Being generous, it has been estimated that to form the simplest protein from primordial oceans, even if we started with the 20 left-handed amino acids and were given 15 billion years to do so, we would wind up with a number of probability in the range of at least 10 to the 60th power.

And just how big would that number be? Well, that number would account for every molecule in the entire universe! And these are the odds of forming one protein when we start with all left-handed amino acids! Yet the simplest cell requires 600 specific proteins!

The probability of proteins coming together naturally is a mathematical impossibility.

Russ Miller is author of The GENESIS Report Series. Register at http://www.new-earth-thought.com to receive FREE his 50 Facts vs. Darwinism e-mail series.

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