[SciFi/Star Wars] Star Wars: The Last Jedi (Episode 8) (80%)

Star Wars: The Last Jedi came out about a month ago and I think that now after two views (distanced by about two weeks),  I can finally write down a final opinion on it. What I can tell, it created some serious divide between the critics and fans. Just look at the difference in scores in Rotten Tomatoes between critics (that lauded it) and fans (that some claims is even worse than Attack of The Clones).
So far, the best and most interesting fan review came from Kevin Smith. A very good hour in which he goes through details, highlighting the good and underlining the bad things about.
I decided to give it a few weeks before making my comments for one reason: the Jedi mind trick that hit me 15 years ago when Attack of the Clones came in screen. At first, I was “Oh yeah, it was awesome! One of the best Star Wars!” and still remember the diatribe from Rafic Djoumni, a former journalist in “Mad-Movies” (a well-respected French magazine about Sci-Fi and horror movies that was my favorite movies magazine). Looking back, the movie honestly did not survived the tides of time and is needed not as good as I remember (please someone remove Anakin meadow scene from my brain!).
ATTENTION————————SPOILERS AHEAD! YOU ARE WARNED!———————————-
So, there is the deal: the movie is good, better that was fans try to make you believe. But it is also not the masterpiece sold by critics. No, it is not “The Empire Strikes Back” quality (still awesome after thousands of watching and almost 40 years in the odometer). There are some good moments, and there are also just scenes I would have cut and I would not even notice I was missing something in the story plot. I feel Rian Johnson wanted to not follow the same steps than JJ Abrams and thought probably it was time for  his own vision of a trilogy. Although this can be a laudable move, it also meant that a lot of things brought by JJ went under the rug.
The movie starts with a bang, right where we kind of left it “The Force Awakens” and it is very intense. Imagine a WW2 bombing operation transposed in a galaxy far far away a long time ago. It was starting very well, but then started to stall at some point. The Rebels try to escape from the Imperial Fleet, only to be caught up a few hours after jumping out from Hyperspace. If you are accustomed to the reboot of “Battlestar Galactica” aka “BSG”, the plot of the first episodes named “33”. I don’t want to spoil much (because this is one of the most awesome Sci-Fi franchise from the mid-2000s I wished was aired in FrenchTV back then) as the Cylons are capable to track “the 12 colonies of Kobol” surviving fleet each time they jump from their FTL (faster than light) drive. Each time after 33 minutes.
This creates a plot in which the Rebels are in a sort of face-off, running out of fuel. Thats sounds a good plot but then you realize it runs on a paper thin. The Imperial fleet has a formidable firepower that would zap the fleet. No, they just stand waiting them to run out of fuel. Kylo Ren is keeping on the rage, only to be disciplined by Snokes. Enough to have Kylo to pick a Tie fighter and attempt a suicide mission on the main fleet vessel carrying General Leia Organa. He literally blew the ships deck with Admiral Ackbar in it sending Leia floating in space. This is where we have another ridiculous scene with CGI as good as “The Matrix Reloaded” (the infamous Playstation2 CGI). One of the sequence I liked however was the appearance of Laura Dern as Admiral Hodo. I was waiting for the “Fuck You, Poe!”, as I am still in all my Twin Peaks mindset and seeing Laura Dern playing the Diane tulpa. Her last move was a last kind of bravado act, going down with her ship as any respectable Captain do after ordering the crew to abandon ship (I almost felt Star Wars was getting inspiration from Trek). The whole sequence was simply a shock and awe, with a complete silence during the scene (remember…….in space nobody hear you scream!).
This scene is enough to questioning where Johnson wants to bring us. I guess it was meant to ramp into the sub-plot of the “Casino planet” that I thought was 45 minutes of major meaning. So I will skip this and go to Lukes plot. We left that with Rey finding Luke and handing him over his lightsaber, the same one he lost on Bespin in the Empire Strikes Back. Here comes the funny part that I liked about, seeing Mark Hamill throwing away the lightsaber and basically saying “enough of this BS”. I liked this whole sub-plot except the Porgs and the nuns. I felt seeing this part of the story was very good and show how the Jedi Council behind his allure of virtue and nobility are not as clean as they want to make things look like. They have sinned in their own way by their overconfidence and maybe also their inability to evolve. Seeing Yoda as a puppet was also a touching moment.
Rey rejoins the whole group and decide to confront Snoke. This is just bringing the second anti-climatic phase of the movie. Snoke dies like an idiot, Captain Phasma dies like an idiot. Both getting the Bobba Fett Mary Sue treatment. Both flattened out as a missed souffle. So we have been waiting two years for something that felt flat like a deflated balloon?
The last quarter of the movie was kind of awesome. It was somehow replaying the plot of the Battle of the Hott system. Seeing the evolved AT-AT and seeing the Rebels cornered brought in this level of stress that was initially here. Then came Luke (sort of), almost coming as a Messiah. And Hell he looked like the Chosen One in a scene reminding us of “The Matrix” Neo final scene, resurrected within the Matrix and capable to stop the  agents bullets and move faster than their moves. Seeing Luke being blasted with all the firepower and stood still made us feel Luke reached the uber-jedi  Rank and was appearing as the Jedi. Only to realize he was transposing himself from a distant galaxy, with the sunset on him. This final scene had some profound meaning for me because it was a direct call to my childhood heroes and it was also meaning that the sun is set on our childhood heroes. Han Solo was gone, Luke is gone and Leia is also gone.
My son loved it, but me I stood at the end of the credits sequence and thought. Maybe I am getting old, maybe I am becoming an old shmuck thats mind is stiffening overtime and incapable to show flexibility. I thought to myself that Episode IX will likely be my last one. I don’t see myself piling up another trilogy and I feel somehow sad to see that Star Wars is becoming a cash cow for Disney, milking it ad nauseam (we are not yet having Star Wars condom but I would not be surprised to have some). Maybe it is time, that as Luke, Han and Leia, I close my eyes on Star Wars.

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[Metal] Happy Holidays! My 15 metal albums and EPs of 2017!

Happy Holidays everyone! As we are now engaged in the last week of 2017, it is a great time for me to go back through my library and pick my 12 albums of 2017. No particular rankings, most of the albums have been reviewed in my blog. I have set the EPs aside since they are not counted as album.

1. January: Xandria – Theater of Dimension

2017 started with a bang with Xandria releasing their latest album and the second album with Dianne Von Giersbergen as front vocals. The motto was “harder, faster, stronger, better”. Damn it was a good album to listen, Dianne being perfect as usual. Unfortunately, the rest of the year was less good for the band. The second leg of the US tour cancelled, Dianne thrown in the residue bin like an used ragdoll. Fortunately, that also means that Dianne is likely reviving Ex-Libris.

2. January: Au Champ Des Morts – Dans La Joie

It is not often that you find French metal bands getting under the spotlight (unless you are Gojira or Alcest), even less French metal bands that sing in French. This was a pure random encounter in my discography, during a Bandcamp campaign (damn Bandcamp is such a great place to discover bands). Mixing elements of black metal and doom, it is a delight to listen to the French lyrics. A must-have in your collection if you are also attracted to the dark side of the Force and needing to find a solace to old wounds.

3. February: FT-17 – Marcellin S’en Va En Guerre

Another Bandcamp pick. Aside from sciences, metal, Sci-Fi and video games, I have another great interest. History! In particular, I am very fixated on World War I: “la Der Des Ders”; “La Grande Guerre”; “La Guerre Des Poilus”. Don’t ask me how my brain clicked on that particular war, maybe because of that field trip during my middle school year at “Le Col Du Linge”, harboring trenches and a museum of this horrible war. The context of military history is not much new and those who know Sabaton know their power-metal hits narrating historical battles. This one is particular. This first album of the melodic death metal band FT-17 (named after one of the first type of French assault tank “Renault FT-17”) is particular as it follow the PFC Marcellin Trouve, writing to his notes his experience of the war, from the joyful draft and heading to the front line to the delusion of the war.

4. March: Midnight Sorrow – Pick A Tale

March was highlighted from the release of the first album by Midnight Sorrow, another French band but this time from my hometown and in the Symphonic Metal genre. I really liked their first EP “At First” and this album took some time to come in, but it was indeed for the better. Coming from their EP, you can hear the maturation of the band in both the musical arrangement (bolder, more confident) and also from Maureen’s voice (in which you can really hear her progress on her vocal abilities). I usually hate when the album is recycling old songs from the previous EP but the band went the extra mile and revisited their songs giving them a second breath with their more experienced sound. It was such a delight to hear that album.
https://youtu.be/syiCMalo44Q

5. May: Seven Kingdoms – Decennium

One thing that I found a bit boring on the US metal scene is the vast domination of the death metal scene and its derived genres (metalcore, deathcore, grindcore…). For some reasons, European favorite genres like Power, Symphonic or Doom are not that popular. So when you have a US metal band playing outside this “terra cognita” it is a welcome. When that same group slap you with a damn awesome album, it is even more welcome.
Hail to Seven Kingdoms, straight out of the Florida panhandle. Florida has a reputation of being the weirdos in the US but they are also home for two awesome US power metal bands: Kamelot and Seven Kingdoms. 72 minutes of a powerful joyride into the meadows of an enchanted land, riding over a robot unicorn, riding in the sunset of a binary star system, slashing an horde of orcs running over using your proton axe to slay the foolish and the foes. If Warhammer 40K should have a soundtrack, I would definitively pick Seven Kingdoms. Just listen to “Stargazer” and tell me you are not all pumped up.

6. May: Alwaid – The Machine & The Beast

Alwaid is another French Metal band that highlighted my album picks in 2017. This second album was quite a departure of their first album “Lacus Somnorium”, that was deeply anchored in atomspheric doom metal. This second is much louder, faster and heavier, more anchored into melodic death but yet with keeping their signature melodics. Again a very good pick and an extensive review of the album on my blog site.

7. June: Neverlight – Nova Red

Neverlight (from Colorado) is this kind of UFOs in my library, standing out by their inability to put them in my classical shelves. Labelled themselves as “dark progressive metal”. It offers a very unique prog metal songs, sharing some similarities with Amaranthe (if you are heavy in the keyboards) but yet very different as it has more darker tones and lyrics. You know what? Enough with the talk. A damn good prog metal album in my library and it pays off to wander into “terra incognito”, just give a try.

8. August: Seven Spires – Solveig

This was another pleasant surprise, as this band straight out of Boston (MA) came out from nowhere and got me hooked up with their title “The Paradox”, directly inspired by Dimmu Borgir and Cradle of Filth. The album per se was very good: engaging melodics, pumping you up with energy and willing you to summon a mosh pit in your cubicle. Playing in different registers, surfing from gothic metal songs like “The Siren/Encounter” to something more mainstream like “The Cabaret of Dreams” to some melodic power metal songs like “Choices” or “Distant Lights”. My favorites remains though “The Paradox” and “Burn”. I leave you with the Paradox official video so can make your choice.

9. September: Paradise Lost – Medusa

Having one of the Unholy Trinity bands release a new album is always welcomed. Paradise Lost “Medusa” is one of these welcome. Adopting a “back to the roots” in terms of the artistic direction of the album, splurging into death doom made this album very special and a hit amongst critiques. It got a very good review on my blog, you can find it.

10. September: Arch Enemy – Will To Power

After 3 years of waiting since “War Eternal”, Michael Amott finally broke the silence and brought on “Will To Power” right to celebrate the 20 years of the band. It was also the second album featuring Alissa White-Gluz. So it was a litmus test for many of the fans and the result was far from disappointing, also a long awaited moment since Jeff Loomis joined the band. It was a hit at first sight with in my opinion a better writing than “War Eternal”. It is brutal (with even some punk influence in the melodics) right from the first track “The Race”, followed by “The World Is Yours” flying into epic melodic power ballads with “The Eagle Flies Alone”. Following the release, the band started the US tour. It was magic! The best concert of 2017.

11. September: Septicflesh – Codex Omega

Septicflesh is a unique band mastering the blending of a classical orchestra with the black symphonic metal style giving you an auditory experience of some of the paintings of Bosch, very finely crafted orchestral arrangement, navigating the different layers of Hell through “Dante’s Inferno”. With Septicflesh, you are welcomed into the Hades Kingdom, navigating through the Styx with Spiro being your guide. A must have if you are attracted by the Dark Side. Considering Spiros and the band are coming nearby for a gig in March, I guess I will add it in the bucket list.

12. September: Clouds – Destin

Whatever I listen, I always come back to doom metal. Behind the darkness and the melancholic tones, I find solace and relief to my mind. There are words I cannot speak, there are feelings I cannot tell, there are wounds that I cannot heal. Doom metal provide me with this opportunity of a catharsis. In sorrow, i found my relief.
This is the case of Clouds “Destin”. Nicely composed, it helps open myself to my mind, let all my sadness, my pain and my sorrow exhale and breath. It allows a deep introspection that few releases can help me cope with these feelings. If you like doom, you MUST try this band.

13. October: Hallatar – No Stars Upon The Bridge

Hallatar is a side project involving various Finnish metal band members including Tomi Joutsen (Amorphis) at the vocals, Juha Raivio (Swallow The Sun) at the guitars and Gas Lipstick (ex-HIM) at the drums. This album is one of the best doom album of the year for different reasons.
Firstly, it is a an album dedicated to the memory of late Aleah Starbridge that left us orphan last year. Secondly, it is an requiem and eulogy album to Aleah, using her poems, giving us a last intimate moment to mourn. The result is simply fantastic and heavy loaded in pain and sorrow. I just hope that this album is closing our mourning on Aleah’s passing and not become an opportunity for anyone to make financial gains on her.

14. November: Evanescence – Synthesis

After a hiatus of over 5 years in terms of album, Amy Lee released “Synthesis” last November. It is per se not a new album, rather it is a an album providing a reorchestration of selected songs spanning through the previous three albums of the band. Some of the songs sound as good as the originals (e.g. “Lithium”), some are even better than original (e.g. “Never Go Back”) and some simply bomb the original (“Bring Me To Life”). It remembers how great Amy is on the vocals and on the piano, and really make us think if Amy decided to “Europeanize” her musical style by taking the best of Symphonic metal.

15. November: Beyond Forgiveness – The Great Wall

“The Great Wall” is the first full-album from the US gothic/symphonic metal band Beyond  Forgiveness (Colorado Springs, CO). I reviewed the album extensively earlier in November so I will comment that much.


The EPs and other albums that were good:
Aside from full-albums listed, there was also the release of “In This Moment We are Free – Cities” by VUUR. With Anneke Von Giersbergen fronting it, it was a great moment to listen in something much heavier than her band “A Gentle Storm”. The album was good, maybe too simple and reminded me a bit the good old times when she was with The Gathering. Maybe a bit too simplistic.
Epica also released an EP “The Solace System” that is a continuation from the “The Holographic Principle”. Again, it was awesome as usual from Epica. You can find more about in one of my previous blog posts.
Another interesting EP I got my hand to was “The Ascension” from Casket Robbery (Madison, WI) formed by Cory Scheider. You may not know Cory but if I am telling you that Cory was part of Luna Mortis, then it will all make sense. Cory put a bit away the melodic death tunes from Luna Mortis and brings in more the brutality into the melodic death. With Megan Orvold bringing the brutal vocals in the line of Angela Gussow (ex-Arch Enemy), you will wish to open a pit of hell inside your living room.

Finally, this year I also got introduced to sludge metal by attending a gig featuring two bands: Rozamov (Boston, MA) and The Ditch & The Delta (Salt Lake City, UT). If you are unfamiliar with sludge metal, it is a blend of doom metal with some Southern death and punk. It has this roughness and Southern flavor that my current doom library is missing. It worth the try. Here two videos are listed from the two bands: Rozamov – “Serpent Cult” and The Ditch & The Delta – “F*ck on Asphalt”

[Stroke/Junk Sciences] Does a needle can save you from a stroke injury? No! No! No!

Some of you have seen this video going around, claiming you can save someone suffering from stroke injury using a needle. The idea behind this video, according to HealthyChoices365, is that a Chinese “professor” claimed this will save the person’s life following a stroke.
This is kind of the thing that, as a basic scientist in the field, boils me for the last few days. First, it is plain quackery. The needle prick has nothing to do with the stroke event: it is distal from the site to have an effect. Second, using this technique on a patient has a direct impact on the patient’s stroke outcome and recovery. Let me explain why this is bullshit and should be called for what it is: A gazillion pile of bullshit that has much more weight that all the coal West Virginia has and had since the geological formation of that region (no pun intended, W. Va has one of the highest number of stroke per capita in the US, since it is Xmas season the lump of coal is simply appropriate).
In brief, stroke is the 5th cause of death in the US (3rd amongst women) and a leading cause of disability. We have two types of stroke: ischemic (85%) and hemorrhagic (15%) with the later accounting for 40% of stroke-related deaths. We estimate that about one US citizen will experience a stroke event every 5 minutes.

1. Stroke 101: Back to basics
In the ischemic stroke, we have a clot (usually formed at the carotid artery bifurcation) that is formed due to the presence of atherosclerotic plaques. These plaques can become unstable and crumble over time. These crumbles are made of clot that navigate through the carotid artery that irrigate the brain. Such clot will act as a plug or a cap, once it reaches a vessel with a diameter smaller than the clot, it will occlude it and block the blood flow.
This create what we call an ischemic situation. In such ischemic situation, the brain is deprived of both oxygen (20% of all oxygen is wired to the brain) and nutrient (in particular, glucose. The brain accounts for about 25% of the total glucose level utilization in the whole body). Neurons are the most sensible brain cells to stroke injury. They cannot adapt to hypoxia (lack of oxygen). Few minutes of hypoxia is enough to cause severe and irreversible brain damage. We estimate about 1 million neurons die every minutes that a stroke is left untreated.
Furthermore, neurons are post-mitotic cells. They cannot divide anymore. When a neuron is gone, it is gone, as well as its neuronal circuitry. You see, each minute matters because what is lost is lost.
Stroke signs can be resumed by the “FAST” acronym: Face droop, Arm weakness, Speech issues, Time to call 911. By the time you are showing signs, it has been already a couple of hours your brain has been starving off glucose and oxygen. It is important that once you have the signs to call 911 and asked the paramedics to direct you to the closest stroke center.
The most important thing to happen in stroke diagnosis is to determine which type of stroke the patient is undergoing: ischemic or hemorrhagic? These two are very different and confusing one with another can have a deadly effect. You don’t want to give a clot-buster to someone with hemorrhagic stroke because it will make the bleeding worse. You don’t want to give a clotting agent to a patient with ischemic stroke because you will increase the risk to develop a second stroke.
The current procedure is the use of endovascular intervention: the neurosurgeon insert a catheter in the femoral artery and using an angiography method to see blood vessels “live on screen” reach the site of stroke injury to either remove the clot or to put a stent in place to stop the bleeding process. From discussing with a physician, this takes about 10-15 minutes once the patient is in the OR.

2. Why this video is BS and should be called BS:
Now, lets see why I call this video BS.
First, the idea of finger prick to treat stroke is BS. We are trying to act on the stroke from a remote site. The thing is, the clotting process occurs in a very local fashion. So trying to act on a stroke with pricking a finger with a needle is mostly useless.
Second, as I said, it is important to know which type of stroke we are treating. You cannot identify which type of stroke is involved just by the clinical signs. You need imaging (CT scan or MRI) to be able to distinguish ischemic stroke from hemorrhagic stroke.
Third, this useless procedure is a formidable waste of time on the patient. As we said, each minute lost is a precious minute lost that will condition the outcome and the recovery. How long should we waste before calling 911 because we noted no improvement: 15 minutes? 30 minutes? 60 minutes? By the time the patient realized this intervention is bogus, his/her chance to survive and recover from the stroke injury are almost close to zero.

To conclude, let me finish this post with a call: PLEASE! PLEASE! PLEASE! Whenever you or a loved one is showing the FAST signs, CALL 9-1-1!!!! Know your nearest hospital with a certified Stroke Center and have the paramedics bring you there. THERE IS NO THERAPY FOR STROKE! OUR BEST BETS ARE PREVENTION (80% of stroke events can be prevented) AND INTERVENTION (by keeping the “door-to-bed” to a minimum).

[Sciences/BBB] Why the vitamin K shot in newborn matters

I have seen the topic of vitamin K (VitK) shot coming over and over in various discussion groups, with some parents weighing the need of the VitK in newborns. One of the main argument in favor for the injection of VitK in newborn is its ability to reduce the risk of cerebral bleeding (cerebral hemorrhage).
I thought a post on this topic would provide a great help in understanding the physiological role of VitK, the consequence of brain hemorrhage and conclude on the importance of the VitK shot.

1.What is the vitamin K?

Vitamin K is a fat-soluble vitamin that is mostly obtained by our gut microbiota and accessory from our food intake (in particular leafy greens and liver).

220px-Phylloquinone_structure.svg

During gestation, the fetus obtains it from the mother, as such vitamin passes through the placenta barrier. Vitamin K plays an important role through its biochemical cycle called “the Vitamin K cycle”. Vitamin K can convert glutamyl residues present in proteins into gamma-carboxylglutamyl residues as depicted in the picture below:

F1.large

Such modified glutamyl residues are present in particular set of proteins called “coagulation factors”. These coagulation factors are important pieces of what we refer as the “coagulation cascade”.
400px-coagulation_full-svg

I know this graph is complicated but what we care here is the final part of the cascade. The presence of intrinsic damage or trauma, we have the activation of several coagulation factors. Amongst those that are VitK-dependent, we have factor VII (seven), IX (nine) and X (ten). Prothrombin, upon activation by factor X  is converted into thrombin, which in turn cleaves the soluble fibrinogen into the insoluble fibrin. Fibrin acts as a mesh and forms a fibrin clot that will patch the bleeding area. This is an important physiological response when you rupture a blood vessel. The coagulation cascade will create a clot that will stop the bleeding process, saving you from a risk of loosing too much blood and entering an hypovolemic shock. One organ is particularly sensible to brain bleed, this organ is the brain.

2. Brain hemorrhage: small numbers, big damage

In this section, I will mostly discuss about brain bleeds in regards of hemorrhagic stroke but you can apply the same pathophysiology to brain bleeds induced by brain trauma. Brain bleeds are the second type of stroke. They account for about 15% of total stroke events, but account for 40% of stroke-related deaths.

subarachnoid-800x416

We have different types of brain bleeds. In stroke, we usually have a type of brain bleed called “intracerebral hemorrhage” (ICH) that happens deep inside the brain. There are other types of hemorrhage called “sub-arachnoid hemorrhage”. In that case, the brain bleeds occurs in the sub-arachnoid space, a space between the brain and the skull. This type of bleed results into an ischemic stroke (due to a lack of blood perfusion in blood vessels beyond the bleed site) and a brain swelling (resulting in the crushing of the brain tissue due to increase intracranial pressure).

During the injury heme (from damaged astrocytes, neurons and red blood cells) is released in the extracellular space. Heme is a very strong pro-oxidant molecule resulting in the formation of radical oxygen species (ROS) such as anion superoxide (O2*-) and hydrogen peroxide (H2O2), which in turn further induce oxidative stress and cellular damage.

The major type of cells that suffers of such damage at the greatest extent are neurons. Neurons are highly sensible to such injury and unlike other cell types neurons do not divide anymore (post-mitotic cells). A dead neuron is a dead neuron. There are some studies suggesting a possible regeneration of neurons in certain brain regions in rodents (mice, rats), yet the presence of an evidence pointing out at similar mechanism in humans are yet to be demonstrated. Furthermore, there is still no evidence that stem cells (including cord blood stem cells from umbilical cord) can provide a repair of such brain region following injury.

As of today, a dead neuron is a dead neuron. The ability of a damaged brain region to recover is very limited.

3. Why Vitamin K shots?

As we just have explained here, we know that VitK is essential in coagulation and we also understood the impact of brain bleed on the brain. Thus, reducing such brain bleed can be done in the short-term by the induction of the coagulation cascade.
As we mentioned, babies get their VitK from the placenta, but by the time they are born, they are already coming with a low VitK. We also mentioned that the VitK is primarily produced by the gut microbiota. It will take weeks if not months for babies to get a gut microbiota that is functional enough to produce the VitK (I speculate that such microbiota is not present until the age of 12 months when baby eat a diet similar to adults). We can speculate that food (breast milk or baby formula) should provide a source of VitK but providing a steady and standardized intake from dietary is near impossible to achieve.
Furthermore, there is no lab tests or techniques that can predict the onset of a brain bleed. Furthermore, brain bleed has a very high mortality rate and very high morbidity rate including cerebral palsy and other brain damage.
Therefore, ensuring a source of VitK right at birth is the best approach to ensure the baby has enough VitK to have a functional coagulation cascade. In case of a brain bleed, we can expect to have a rapid response of the body to ensure a emergency clotting process ongoing until the doctors can intervene and stop such bleeding to happen and clean any possible brain bleed.
This is why it is important to opt-in for a VitK shot. Once a brain tissue is damaged, there is no evidence yet that there is regeneration of such area. Neurons do not divide anymore by birth and there is no evidence yet of stem cells (including stem cells from cord blood) able to repair such damage.

 

[Punk] Brian Deneke 30/09/1978 – 12/12/1997

Today marks the 20th anniversary of the death of Brian Deneke. His death did not made the international news much, but for those that live in Europe, his death is sharing similarities with the death of Sophie Lancaster (died on 08/11/2007). Many metalheads know about her death, enough to have Delain dedicated a song on her named “We Are The Other” in their album named similarly. Both deaths share the same motivation: murdered because they were different, because they were not fitting the mold of society, because they were ostracized by their attire and their style, because they wanted to live their lives as teenagers using music subgenres as a vehicle for their catharsis. Brian found in the punk culture a liberating moment, Sophie found in the goth culture a liberating moment. Myself found mine in the doom metal culture.
I heard the story of Brian only recently, as a stranger, from my few years living in Yellow City. Some call it Bomb City, because of the nearby Pantex assembly that constitute some vital part of the economy. But I felt in the story of Brian, the same story that many others that do not fit to the mold of the society feel: being labelled as a misfit, as an outcast, as an indesirable of the society.
Interestingly, Brian and me share roughly the same age (+/- 12 months), come from the same generation (Gen Xers) and have been in our troubled teenage years in the same time. We both are not actual to the punk movement, if we consider the movement “golden age” was in the end 70s-beginning 80s. Yet, the punk movement was alive and kicking proud in the 90s. Some classmate embraced punk as a way to rebel against the system, embracing some anarchist ideas. “Fuck the system!” was the motto. I was like Teflon to embracing punk: it did not stick long on me. I rather was seeking the melodic riffs of the other major genre that grew alongside the punk movement: the New Wave of British Heavy Metal. I was driven by the escaping and incensing tunes of Iron Maiden, swinged by the lyrics of Bruce Dickinson and the guitar melodics. Sure, I was an outcast, I was a nerd and I was the dude that sit quietly in a group of friends. But what I experienced was nothing to what Brian and many teenagers in the US experienced.
As an European, the only exposure to US teenage years was through the TV: you had the posh and falsely glamour pictures from “Beverly Hills 90210” or “Melrose Place”, the funny “Saved By The Bell” (although sometimes opened discussion to serious matters) or what appeared more realistic as “21 Jump Street” (by discussing some real issues). But the one that was really in phase with me was MTV “Daria”. She was also an outcast in her sense, nixing being part of the cheerleader team or being the girlfriend of the football star. She was also a punk at heart along with her friend Jane, without having a crush on Trent (Jane’s brother) that was playing into a rock band during the weekends. It also showed me that the meaning of belonging to a tribe in the US was really much more amplified in the US than it was in Europe.
Where I had no pretension for a music career, Brian saw himself part of the local punk scene dreaming of becoming a leader for a punk band that could make a living of his art. The events that lead to Brian’s death are unknown to me and mostly garnered from reading on different sources.
It seems all started on the IHOP facing the former Western Plaza mall (what seems to be the current strip mall located on I-40@Western corner). On Saturday December 6th, an altercation occurred between Dustin Camp (a honor student and star football player at Tascosa High School) and John King, a member of the local punk scene. For those who are not familiar, Tascosa High School is usually considered one of the most preppy public HS in Yellow City, surrounded by the posh Tascosa neighborhood (since the Colonies neighborhood claim the title of “posh neighborhood). There are contested claims that Camp tried to run on King and his group with his Cadillac, some claiming King hit Camps windshield with a baton. On Friday 12th, Camp and King (alongside their group of friends) set a showdown in front of the same IHOP at 11:00pm. During the fight, Camp retreated in his car and ran over Deneke in an apparent hit-and-run.
The trial was set on Camp with a first-degree murder. The defense attorney, Warren Clark, apparently try to divert the attention of the jury by ostracizing and trying to put the blame on the punk community. Considering the Yellow City community, putting blame on the misfits is an easy target by portraying them with some infamous cliches: “They are lawless, they worship Satan, they are punks.” These are the same kind of stuff we metalheads have to go through: our music is noise, garbage. We are Satan-worshipper, we have tomb-destroyer. We are evil incarnate.
The trial concluded with Camp found guilty as involuntary manslaughter, 10 years probation and $10’000 fine. This is a very mild sentence for someone that voluntarily (according to witnesses) run over Brian and left the crime scene. This case has possibly some signs of “affluenza” in which the social position of the person prosecuted is used to downplay the severity of the crime (“He is a good boy! He is in the Honors list! He is the football star player!”), something we have been already seen. Nevertheless, he was arrested in 2001 for underage drinking, followed by charges on false statement to police and ultimately sentenced in September 2001 to 8 years in prison for violating his probation.

More recently, a movie documentary named “Bomb City” retracing the story of Brian Deneke has received some remarkable standing ovations and awards at various film festivals. I would strongly recommend to watch it and I hope to attend the local airing.

Although the punk and metal scenes rarely mingle (although some can argue that thrash, death metal are intertwining of punk and metal), the small scene in Yellow City make us closer. We don’t have much gigs in town, so when we have some local bands performing in a bar, it is more than welcome. I try to think that what if Brian was still amongst us, maybe I would have been sitting in a bar watching him perform and enjoying his gig.

However, I will never have that chance. I really feel sorry for Brian’s parents about what happened to Brian. I wished I could give them “my sincere condolences” even 20 years after the facts. Rest in Peace Brian 😦

[Metal/Melodic Death] Arch Enemy @ Sunshine Theater (Albuquerque, NM – 12/02/2017)

It has been a bit more than three years since I discovered @ArchEnemy via their album “War Eternal” and it was basically a love at first sight. It was a very big surprise because I am not much driven into death metal bands, but what makes Arch Enemy unique is the remarkable Michael Amott guitar melodics, now seconded by Jeff Loomis (ex-Nevermore). I even got into the feud between “team Angie” versus “team Alissa” (spoiler: Alissa really gained a lot of experience since War Eternal and you can get that from “Will to Power”)
I quickly ended up getting the whole discography but one thing I could not get is to attend one of their gig. Arch Enemy tours a lot in Europe, but having them tour the US is damn hard. So when they announced they will tour and have a stop in ABQ (that cuts my ride to 4 hours instead of 5.5 hours), it was a bliss for me. Top it with a show on Saturday night and that was just having the perfect astral alignment to attend it.
The only issue I have was the line-up: Fit for an Autopsy (Deathcore, Jersey City, NJ), While She Sleeps (Metalcore, Sheffield, UK) and Trivium (Groove Metal, Orlando, FL). Nothing that talk to me much, especially when you were bottle-fed with some fine European metal bands. I find it interesting the relative cleavage in the metal styles between the Old and the New continent: the former is complex, well refined and musically challenging whereas the later often is more brutal and primal in its composition. TL:DR, none of the lineup bands got my interest, they failed to impress me so I will not talk about them and move to Arch Enemy.
What was interesting though was the number of folks that left the show right after Trivium, especially teenagers and college kids. This was just like any swimming pool in a hotel: time for kids and family ran out and time to start the adult swim.

IMG_0954

Oh boy, 75 minutes of pure joy (and few bruises and weightlifting :p) and also a chance to sneak in closer to the front row. We get into the performance accompanied by “Set Flame  To The Night” with Daniel coming behind the drums and starting them like a horde of B52s flying over with the guitar riffs of Michael and Jeff with “The World Is Yours”. You know what, just watch it:
https://youtu.be/0GkXBRXXMv4

This is Arch F**king Enemy! 75 minutes of rage, furor, mosh, marvelous performance of the band! Alissa clearly walk the walk, learnt from the mentorship of Angie. Damn it feels good to listen the band live.
The band played through their whole repertoire from “Wages of Sin” until “Will to Power”.

 

 

We started with “The World Is Yours”, followed by “Ravenous” (not much my favorite though), “Stolen Life”, “My Apocalypse”, “War Eternal”, “Bloodstained Cross” (Ohhhhh yeah! As brutal than Angie!), “As The Pages Burn”, “The Eagles Fly Alone”, “We Will Rise”, “Avalanche” followed by a solo by Jeff transitioning into “Snow Bound” (one of the best guitar solo by Michael on “Wages of Sin”) and finally concluding to “Nemesis” (the classical AE song and also a good metric to compare Alissa versus Angie).
If I have to pick a concert that was awesome to me, this is THE CONCERT that I found the most awesome. Really looking forward to see them again soon!

[Neurosciences/Aluminum] Does the latest paper from Exley show a link between ASD and aluminum?

Someone brought my attention today about the most recent Exley paper out in the press titled “Aluminium in brain tissue in autism” (the title could have been better but well….) and published in the journal “Journal of Trace Elements in Medicine and Biology“.
Let me put this straight, this is not a paper that has evidence of scientific fraud or data manipulation. There is no duplicated images, no suspicious blots. The problem I have with this paper is its deep experimental flaws and data analysis that nonetheless should not have passed through the peer-review filter.

  1. Before we dive into the paper, lets put the paper into context
    Lets just put the paper in the context. It was received on October 26th (Thursday). Came back in its revised form on November 21st on Tuesday and accepted for publication on November 23rd (Thanksgivings for the US, but since the editor-in-chief (EIC) is in Europe no Thanksgiving here). Let that sink it a bit: in a bit more than three weeks, it got send to review, came back from review and got revised in 26 days. In my standard of reviewing for journals and publishing my papers, thats some faster-than-light peer-reviews. I usually wait 4-5 weeks by the time I submit mine and get the editor reply to my submission with the infamous reviewers comments. Does a fast-reviewed manuscript means a bad manuscript? Not necessarily, but it can mean that maybe the peer-reviewed was not optimal, rushed or even worse just botched. Based on the quality of the data presented, I am leaning towards a botched review. Thats quite disappointing because the journal holds a decent impact factor (~3 for 5-year impact factor) and you expect an okay review.
    Then comes another problem. Exley published this paper (as well as few others) in the journal…..in which he holds a seat in the editorial board. Nobody can exclude the possible conflict of interest. Consider that: if you were an EIC, would you provide the same rigor and objective decision on a paper submitted by a colleague sitting in your editorial board than a paper submitted by Doe and colleagues?
    Not forbidden, but if you can avoid it, avoid it. Transparency is key and publishing in diversified journals (unless it is society-official journals) is an indicator of an healthy research.
    Finally, the last thing to keep in mind before I deconstruct the paper is the funding source. According to the acknowledgment section “The research is supported by a grant from the Children’s Medical Safety Research Institute (CMSRI), a not-for-profit research foundation based in Washington DC, USA.”  Behind the fancy name is just another anti-vaccine foundation that will play “the vaccine safety” card to peddle their pseudosciences. So we can claim that Exley is a shill for CMSRI, since he received monetary support for his research. Does that mean the research is completely bogus? No, but it means it will require further scrutiny, especially when the claim of the study goes against the consensus in the field (aluminum in vaccines is safe).
    Same goes if a study funded by Big Tobacco claimed the absence of correlation between lung cancer and smoking or if Big Sugar claimed the absence of correlation between type 2 diabetes mellitus and consumption of sweetened beverages.
  2. So what is wrong with this paper?
    For those who wants to read the paper with me, you can download it here (I assume it is open-access, so you should not have an issue with the paywall). Exley has a publication record on aluminum, especially when it comes to its possible ecotoxicity and the impact of aluminum on certain biological processes.
    The introduction is damn short, half a page of a double-spaced document but set the tone, this study will investigate the relationship between autism and aluminum in the brain.
    Samples are obtained from the Oxford Brain Bank, but felt short to indicate the source of the tissue (like a catalog number) and how this source of materials was complying with the institutional review boards (IRB). Basically, for any research involving human subjects or human tissues, you have to comply with the IRB that such specimens are used for a certain and defined use and foremost been anonymized.
    We have 5 patients that were diagnosed as on the autism spectrum and immediately we can pinpoint an important issue: there are no controls and that’s one of the big and unforgiving flaw of this paper.
    The authors then used two techniques to localize and quantify the Al in different cortical regions (and sometimes hippocampal regions). They have used three technical replicates (random sampling from the same cortical lobe) for measuring the Al content using an atomic absorption spectrometry and used lumogallion (aka4-chloro-3-(2,4-dihydroxyphenylazo)-2-hydroxybenzene-1-sulphonic acid, a fluorescent dye initially described to localize Al in plant roots). This dye have an excitation/emission spectra close from FITC/Alexa Fluor 488. It has been also used for live cell imaging , in particular to study how macrophages process Al present in vaccines adjuvants (http://www.sciencedirect.com/science/article/pii/S0022175915001222).
    Considering the equipment mentioned in the method, the microscope used provides the right excitation bandwidth filter and provide a long pass emission filter for anything over 510nm.Then things get weird, in the result sections, the authors mention the following:”We examined serial brain sections from 10 individuals (3 females and 7 males) who died with a diagnosis of ASD and recorded the presence of aluminium in these tissues (Table S1).“Where is the number coming from? Why don’t we have the same numbers in the Materials and methods?The other problem is the over interpretation of the data. To be brief, the lumogallion will show some punctuated pictures. The authors show some brightfield pictures overlapping to show the tissue structure but does not really help the reader. A DAPI stain (to stain cell nuclei) as counterstain would have been much more informative, it would helped to distinguish background noise from possible Al inclusion. Again, keep in mind we have no controls. The other issues with immunostaining is the high risk to cherry pick the data. You will be naturally inclined to show the presence of a positive risk but this cannot be used for quantitation. Thus, the use of the second method is welcomed as a complementary technique.
    For those not familiar with fluorescence, there is an important notion to keep in mind when analyzing the data: ensuring you keep the same exposure time, the same brightness or contrast and foremost have a negative control to set your exposure time. You can see a sketch explaining here on one of my fluorescence staining (based on my data, I concluded the expression was weak if not negative).

    Slide2

    The background subtraction is also a bit weird. I acknowledge the assessment of autofluorescence is a good control, but you expect to see a low staining. But foremost, you cannot overlap two distinct slices, as proximal as it can be. For instance, in Figure 1, you see some lumogallion staining and below the fluorescence  from the “control” using the adjacent slice. The lumogallion also seems to have a very high background.
    Picture1
    It seems lipid-rich environment increase dramatically the fluorescence of lumogallion (if you look at the spectra, the dissolution of the dye in Triton-X100 solution (b, a detergent) dramatically increase the excitation and emission spectra compared to water (a)).
    What I found troubling is this sentence in the results section: “We examined serial brain sections from 10 individuals (3 females and 7 males) who died with a diagnosis of ASD and recorded the presence of aluminium in these tissues (Table S1). Excitation of the complex of aluminium and lumogallion emits characteristic orange fluorescence that appears increasingly bright yellow at higher fluorescence intensities. Aluminium, identified as lumogallion-reactive deposits, was recorded in at least one tissue in all 10 individuals. Autofluorescence of immediately adjacent serial sections confirmed“.
    If you are a bit a fluorescence microscopy savvy, you know that the “emission color” we see in the objective is never caught by the CCD camera. These camera have in the most majority a B&W output for the simple reason that they have a much higher sensitivity than color cameras. You can always re-create colors in the micrograph pictures using various “lookup tables” (LUTs) that will give a pseudo color based on the level of grays. This is very useful when you samples different excitation/emission channels (for instance, samples stained with DAPI and two antibodies, one conjugated with Alexa Fluor 488 and the other with Alexa Fluor 546 or further down).
    The problem inherent with fluorescence is you can make thing fluoresce or end up with a false-positive signal if you increase the light beam (usually never happens because it is set) or if you increase the exposure time of your camera (this is the most common issue). As you increase exposure, you increase the risk to capture non-specific signal like autofluorescence signals.
    The other problem here is how to explain this sudden shift from orange to yellow?  This seems more like a subjective observation than something caught on camera.  That can be due to different things. You can have some bleed-through of the dye that is normally emitting in a certain wavelength but if it is strong enough can appears in neighboring emission channels. This thing rarely happens with a good fluorescence microscope that have defined filter cubes that allows the diffusion of certain emission wavelengths (for instance, my microscope have a DAPI, Alexa Fluor 488 and Alexa Fluor 555 cubes that only let the respective emission wavelengths  with 20nm-margin error to cross through the objective and reach the camera and binocular).
    Usually, we have to deal with bleed-through when you use flow cytometry and usually is solved using fluorescent dyes latex beads and by following a protocol called “compensation” (this has the result of removing any noise and keeping only the signals).
    We cannot also exclude that such fluorescence is just an autofluorescence from lipofuscine inclusion bodies. Lipofuscin is a lipid-based compound naturally produced by our cells. It has an important concentration in the central nervous system, however it is normally cleared out by cells. Failure in the clearance of lipofuscin is associated with different diseases called “lipofucsinosis” such as Batten’s disease. Even the author admit the possible presence of lipofuscin inclusions “Intracellular aluminium was identified in likely neurones and glia-like cells and often in the vicinity of or colocalised with lipofuscin (Fig. 5).” Lipofuscin is also capable of autofluorescence, although it is more in the wavelengths matching DAPI. Lipofuscin has an excitation/emission peaks at 360 and 435nm respectively but has been reported to also show fluorescence at 510nm when excited at 488nm (https://www.sciencedirect.com/topics/neuroscience/lipofuscin).
    Compared to the lumogallion excitation/emission spectra (507/567), we cannot exclude the presence of a phenomenon called “FRET” (Fosterman Resonance Energy Transfer) in which the excitation of lipofuscin (as the microscope excitation bandwidth is 470-495nm) provide enough energy to the photons emitted by the lipofucsin to excite nearby lumogallion dyes. Because the microscope setting used in this paper has no restricted bandwidth (it let pass any photons harboring a wavelength of 510nm and more), it may explain this orange-to-yellow transition noted by the author. The presence of a DAPI nuclear stain would greatly helped to identify this region as grey matter (rich in cells) or white matter (rich in lipid-rich myelin sheets). Thus, we can legitimately questions the nature of these as it these punctae labelled as “Al inclusion” are simply lipid inclusion or some artificial noise due to the tissue processing. This is where controls come as critical, it can help you sort the signal from the noise.

     

    The second big issue with this paper is the over-interpretation of what the experimenter see. The experimenter wants to see Al inclusion in monocytes? So be it: “Aluminium-loaded mononuclear white blood cells, probably lymphocytes, were identified in the meninges and possibly in the process of entering brain tissue from the lymphatic system“. Or maybe these are astrocytes, or neurons, or microglial cells, or blood vessels….or whatever the author wants to believe in: “Aluminium could be clearly seen inside cells as either discrete punctate deposits or as bright yellow fluorescence. Aluminium was located in inflammatory cells associated with the vasculature (Fig. 2). In one case what looks like an aluminium-loaded lymphocyte or monocyte was noted within a blood vessel lumen surrounded by red blood cells while another probable lymphocyte showing intense yellow fluorescence was noted in the adventitia (Fig. 2b). Glial cells including microglia-like cells that showed positive aluminium fluorescence were often observed in brain tissue in the vicinity of aluminium-stained extracellular deposits (Figs. 3&4). Discrete deposits of aluminium approximately 1m in diameter were clearly visible in both round and amoeboid glial cell bodies (e.g. Fig. 3b). Intracellular aluminium was identified in likely neurones and glia-like cells and often in the vicinity of or colocalised with lipofuscin (Fig. 5). Aluminium-selective fluorescence microscopy was successful in identifying aluminium in extracellular and intracellular locations in neurones and non-neuronal cells and across all brain tissues studied (Figs.1-5). The method only identifies aluminium as evidenced by large areas of brain tissue without any characteristic aluminium-positive fluorescence (Fig. S1).
    This is the second big mistake of this paper. If the author wants to make the claim he proposed here, then he has the obligation to show a counterstain using selective markers for neurons (e.g. MAP2, bIII-tubulin, NeuN….), astrocytes (e.g. GFAP), microglial cells (CD11b), leukocytes (CD3), macrophages (CD45), blood vessels (e.g. PECAM-1, claudin-5). This could have been easily performed (using a secondary antibody conjugated with Alexa Fluor 555 or better Alexa Fluor 647)  and would have give support to this claim.
    If the author can identify cells by the naked eye, he is either equipped with  Superman X-ray eyes or he is just imagining things.

    The discussion quickly gets into an anti-vaxxer diatribe and throws the minimal amount of scientific data under the bus.
    For example, the author throws this sentence as is: “We recorded some of the highest values for brain aluminium content ever measured in healthy or diseased tissues in these male ASD donors including values of 17.10, 18.57 and 22.11 g/g dry wt. (Table 1).” Firstly, where does it get this data? You cannot sum technical replicates, you have to average them (even with considering the huge variability between technical replicates). Secondly, how can the author make a claim like this without providing values from controls (well there are no controls) or from the literature. It is like “we have recorded the highest amount of leukocytes in ASD patients blood samples with values of 11.3, 12.0 and 11.5 x10e3 cells/mm3.” I cannot make an interpretation or conclusion without knowing the reference from the normal population (normal range 4.5-11x 10e3 cells/mm3) or from control groups. The average Al level was 2.38-4.79 microg/g tissues in male ASD and 1.15 in the female ASD patient. Such levels were very similar to those reported in samples from patients suffering from familial form of Alzheimer’s disease.
    Slide3

    The data is interesting but we are lacking additional female samples to make a claim as he did: “All 4 male donors had significantly higher concentrations of brain aluminium than the single female donor.” He lacks the proper conditions to run the statistics (you need same number of patients in male and female to make such claims) and even the important inter-individual variability makes it unlikely that he could achieve the statistical significance. This is a statement that would put a graduate student in shame for overconfidence in the data.
    Then goes the tirade “What discriminates these data from other analyses of brain aluminium in other diseases is the age of the ASD donors. Why, for example would a 15 year old boy have such a high content of aluminium in their brain tissues? There are no comparative data in the scientific literature, the closest being similarly high data for a 42 year old male with familial Alzheimer’s disease (fAD) [19].” (another Exley paper published…..in the same journal). We are dealing with the same issues (lack of controls, huge variability in the technical replicates…..).
    Now if you plot the average patient Al levels agains the age, regardless of the condition, you end up with an homogenous cloud. Now, two things have to be noted here: seems there is no impact of Al levels based on the disease (only age seems to matter between ASD and AD) and there is no correlation between increase in brain Al and age, at least in the very small sample size.
    Data 2

    No pun intended, but the data scatter looks vaguely like the United States map. Again, it shows the need of data from asymptomatic patients to estimate the burden of Al in the brain.
    Since we have not access to Al content in the brain, we have to see some values in the literature. A study by Andrasi and colleagues (https://content.iospress.com/articles/journal-of-alzheimers-disease/jad00432) provide some Al levels in control samples. According to their study, the average Al content in control samples were between 1.4 to 2.5µg/g dry tissue. We are indeed not far from the value reported by this study, especially when you consider the important standard deviation in these samples.

    Maybe it is also to consider the other study by Exler on Al level in brain samples from patients associated with familial form of Alzheimers disease (fAD) and familial dementia. In that study, all reported with Alzheimers (some with early onset, some with late onset based on age), the Al values reported were ranging from 0.34microg/g tissue (male) to 6.55microg/g (female, presenting a mutation in the PSEN1 gene, a known gene in FAD). So are we just measuring noise and try to extrapolate data from noise? Thats some bold statement that should have been smashed already by a decent reviewer in the field of neurosciences.
    But seeing these two papers went through in a apparent free ride is not looking good for the journal integrity.

  3. Conclusive Remarks
    To make a claim is one thing, to back it up with robust data is another thing. I think Exley jumped the shark a while ago and started to aluminum as the big bad wolf in every little things. But a wolf can be tamed, kept out from showing danger to the community and somehow co-exist. But for Exley, like Shaw, like Gherardi, aluminum is the devil incarnate. God forbid it has been used for 70 years and showed barely more than simple coincidence in its association with some disease, aluminum is their dead horse that worth being beaten again and again. If your funding sponsor will give you money for showing a link between aluminum and autism, lets give them what they want. Ethically it is insane, but when you need to keep your lab and your faculty position afloat, sometimes making the pact with the devil and throwing the scientific integrity and the philosophism that is given to you  following your thesis defense can be tempting. Sometimes, it feels that anti-vaccines researchers are like Faust and succumbed to the offer made by Mephistopheles offer. But this come with a price and a hefty price to pay: the loss of your integrity as a scientist.
    So my question is what is coming next to patients on the spectrum: does this study will be used to support the anti-vaccine agenda (another reason to yell “Aluminum is a chemikillz” in parenting groups?) and breakdown the herd immunity? Bogus remedies by bleach enemas and drops (the infamous CD/MMS)? or give a support to chelation therapy? gluten-free/casein-free diet? Or like Exley once claimed have these people drink ad nauseam silicon-rich water like Fiji water or Volvic water with the magic claims that the silicon with drain your brain from the Al contained inside it?
    This kind of deeply-flawed studies, lacking proper controls and driven by an ideology over the facts are dangerous because they prey on the meek and enrich modern snake oil sellers.