[Vaccines/Junk Sciences] “Murine hypothalamic destruction with vascular cell apoptosis subsequent to combined administration of human papilloma virus vaccine and pertussis toxin” (Aratani et al., Sci Rep 2016 – RETRACTED) Lesson from a paper that went completely fritz on the scientific method

You maybe heard about the recent retraction notice of a study published in Scientific Reports that raised concern about the safety of Gardasil(R) (HPV vaccine) and got retracted this week. Another anti-vaccine paper that bit the dust. I would have say, I am not surprised at all. Anti-vaccine studies have this very annoying habit of either being a proven fraud (remember the latest Shaw paper?), botching the experimental protocol with omission of proper controls (thats the Exley paper I have reviewed) or conveniently sweeping under the rug some data that are not fitting the narrative (that goes for one recent paper published by Gherardi).
But this one is interesting at several levels, because there is a bit of blood-brain barrier in  it, and also adds to the list of papers retraction in Scientific Reports and recent threats by scientists in the editorial board to resign from their positions due to ambiguous and unjustified decision on a flawed paper (Disclaimer: I have a study authored in this journal and I have peer-reviewed for them a couple of times).

To be honest, I only heard about this paper during the last weekend and took some times to read the paper. I will be honest, I don’t see any scientific fraud in the sense of data manipulation. What concerns me is how such a botched study could even pass through peer-review process? Considering I self-impose a quality of standard in my manuscripts and still get challenged by peer-reviewers, seeing such junk studies getting a free pass is a bit vexing. I agree that open-access may not have the same stringency in terms of peer-review filter but considering Scientific Reports as part of Nature Publishing Group, you expect a rigor found for any Nature-related journals applied in this journal too.

But lets go through the paper, it is retracted but you can still access it here.

What is the wrong with this paper?

1. The experimental design in terms of groups

The first problem arises from Figure 1.

Aratani_Fig1

We have six groups: vehicle (PBS), pertussis toxin (PTX), Gardasil(R) (MSD, HPV vaccine 4-strains) (G), G+PTX, EAE and EAE+PTX. Let’s breakdown first these oddities.  Why the author has included a PTX group, even more adding PTX with Gardasil? There is not much explanation in the text explaining the rationale (also the writing style is odd, very odd. I completely understand that the first author is not a Native English speaker. As an ESL myself, I completely understand that). Also, I am not aware about a higher risk on contracting pertussis upon vaccines.
The second aspect is the use of the EAE mouse model. EAE stands for experimental autoimmune encephalitis. It is the “gold standard” for a mouse model of multiple sclerosis (MS). The idea behind is to inject a brain protein (myelin basic protein or MBP), which will trigger an immune reaction (as the brain is a immune-privileged organ) and result in symptoms similar to MS. I would understand to compare the incidence of Gardasil(R) on MS patients by comparing EAE mice versus non-EAE mice but that is never the case (they even administer PTX to a sub-group).
So here we already start with a wrong experimental design: it just make no sense. A more rationale approach would have been the following:
Vehicle (PBS), Gardasil (G), EAE, EAE+G. That would have saved two groups and precious lives sacrificed in another useless study.

2. The experimental design in terms of statistics and power of analysis

Another important issue is the blatant dismissal of consideration of biostatistics and the power of analysis in the experimental design. For those that are not familiar with scientific research, you have to ensure you have a statistical meaning to your data to ensure the effect observed is real and not due to simple coincidence. This statement is especially true when working with vertebrates animals. Any animal experiment has to be approved by the institutional IACUC that ensure you have a clear idea of what are the purpose of your experiments, how you will ensure a humane treatment to animals and also have an optimal number of animals to achieve a statistical significance.
An important aspect for in vivo (animal) studies is to achieve at least a sample size of 8 or more animals per group (n=8). From Figure 1a, we have already a violation of this as only the G and the G+PTX have enough animals (n=14 and 21 respectively). All other groups are below the n=8 threshold. In addition, you have very different number of animals per groups (control has n=6, EAE has n=5) making the statistical power weak and also restricting the use of common statistical methods such as the use of ANOVA (ANOVA recommends that all groups have an equal number of samples).

3. The experimental procedure and treatment

This is where the firestorm came in: the experimental data. So lets bring this to the table: “Groups of 11 week-old female C57BL/6 mice were intramuscularly administrated 100 μ l of Gardasil or phosphate-buffered saline (PBS) for a total of five times. Ptx was intraperitoneally administrated 2 and 24 hours after immunization. The Gardasil vaccine or Ptx were administrated at 2- weeks or 4-week intervals“.
A key element in a paper is the methods section and this one utterly failed. Based on this information I have absolutely no idea why they injected five times (Gardasil immunization is maximum 3 times), why they injected the PTX right after the immunization (2 and 24 hours, suggesting a double-induction) and when they injected the Gardasil and PTX (how do they separate the 2-weeks versus the 4-weeks? When did they started?).
Also the use of 11 week-old female is not reflective of a human case scenario. If we approximate 1 human year to about 3.6 mice-days, you would expect to use young mice (males and females, to have a gender-balanced study) that are about 6-weeks old (~43.2 days). That would be about 12 years, the age of puberty.
Here we are basically injecting HPV to adult females, which is known to not provide an additional benefit as such population may have already been exposed to HPVs.
The next problem is the injection dose. It is 100microL, thats the equivalent of 0.1mL. A single dose of HPV is 0.5mL. Lets ignore the scale law and assume a mouse is an equivalent to a human. A 50th percentile weight at age 12 is about 40kgs. Lets assume a 6-weeks old mice to be about 20g.
If we assume 0.1mL injection to a 20g mouse, then the human dose-equivalent would be about 200 dose-equivalent injected at once! This is a serious issue because there is absolutely no chance that such things to happen in a lifetime (at grand maximum you may have 3-4 HPV injections, spaced in time). Also, if we assume the age scale, we are expecting to have mice receive their two doses within 48 to 96 hours, not 2 to 4-weeks.
I am not even entering the rationale to inject PTX right after immunization, which is utterly no-sense and just scramble defining the effect of HPV versus the effect of PTX. Another disastrous example of how this paper was flawed from the beginning.

4. Failure to report weight and clinical score

If we want to follow an EAE protocol, it is important to show the evolution of animal weight over a period of times (up to 15-21 days) as well as a clinical score. The clinical score is a well-described protocol in which features found in EAE mice are score from mild (tail flaccid) to severe (inability to move hindlimb or complete immobility).
These two graphs are almost present in any EAE paper outside in the literature.
I assume this is what Figure 1b and 1c wanted to show but very poorly. Indeed Figure 1c does not really show up anything. We dont know when these data have been taken, we have no idea about the onset time of symptoms and furthermore we have no indication of a statistical differences. This is already a waste of data.

5. The constant cherry-picking of the data and incomplete picture

The methods used are honestly laughable: some hematoxylin-eosin staining (a common histological stain that does not tell much unless you have massive brain damage or the growth brain tumor),  Kluver-Barrera staining (for myelin staining), TUNEL stringing (for apoptosis), a behavioral test relegated in Supplementary Figure S1 (in which the author thinks that a P-value of 0.1 has a statistical meaning).

Aratani_Fig2

Aratani_FigS1
Where is the Evans blue extravasation staining to show a disrupted BBB? Where are the GFAP staining to show astrocytes activation? Where are the CD11b and F4/80 staining to show microglial cells activation and macrophages infiltration? Nowhere to be seen. We have to comptent ourselves with some miserable histological staining in Figure 2 and 3. Also no-one of the data about EAE is never shown past Figure 1. Figure 4 is even more laughable as the author only shows the staining of the G+PTX, giving the middle finger to the reader to how such staining looks like in vehicle, or G.

Aratani_Fig3

How can the author be confident that it was the Gardasil treatment, not the PTX treatment (despite being mentioned as a BBB disrupting toxin) being the sole contributor of all this?

6. Conclusions

Another anti-vaccine study, another case of botched science resulting in a junk paper, the sacrifice of animals over a useless experiment. That should not have been passing through the peer-review filter at all because of its deficiencies, yet was able to go through. If I was the reviewer behind it, I would have been ashamed to have this paper not outright rejected for major flaws in the study. Should we assume that the author recommended some complacent reviewers  to this paper? Or should we question the integrity of the editorial board in accepting papers for publication that fail to address some scientific integrity? Again, anti-vaccine studies shows that they cannot challenge vaccine safety and can only make fool of themselves by producing junk studies like this time.

The first and senior authors of this paper produced a paper that is so bad, they should feel ashamed to even had published at first.

 

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[Metal/Gothic] Theatre of Tragedy – Aegis (20th Anniversary Release)

Today marks the 20th anniversary of the release of the second album by the Norwegian gothic metal band Theatre Of Tragedy. Listening to it reminds me how great the 90s was for the gothic metal scene and one of the most prolific period in which we have seen most of the metal divas entering the scene and in their trails new genre of metal in Europe and in particular from Scandinavian countries (Norway, Sweden, Finland).
Indeed, that period was the golden age for the second wave coming from Norway. This time a much different style and approach than the first wave made notoriously famous by the church burning and the intestine hatred between some black metal bands (You cannot go without mentioning the name of Varg Vikenes).
This second wave brought one of the most refined sounds to be heard in gothic metal by two Norwegian bands (Tristania and Theatre of Tragedy) supported by some of the most talented feminine voice in metal.
One of them is Liv Kristine, certainly one of the most hypnotizing voice in the “female-fronted metal bands” (I hate that word but I use it applied to the context of that period).
In this second album, named “Aegis”, Theatre of Tragedy learnt from their first album and perfected their sound and Liv her vocal performance. The result? A masterpiece of Gothic Metal. The album is a 10-track album spanning for about an hour.
We get aspired into it straight by the first title “Cassandra” wrapped by the mysterious atmosphere and the vocals of Liv. It is rapidly followed by “Lorelei”, that is more fast-paced than “Cassandra” but in perfect manner. “Angelique”, takes more into a melodic ballad that is reminiscent of a Lacuna Coil. A very relaxing track to listen. “Aoede”, the fourth track, is original and maybe very disorienting because at first we don’t know if they sing in Norwegian on this track until you read the lyrics and assume they wrote in Old English. Thats give the extra amount of mystery and stimulation. The fifth track, “Siren”, is certainly my favorite. By its composition, by its lyrics and by the voice of Liv Kristin. Definitely Liv is the Siren in this song, as we can only succumb to her voice and drown in the waves of melancholy and sadness. I would give any day a shoot to a “Theatre of Tragedy” to a “Leaves Eyes”. This is the kind of track that makes this album a must-have in your collection.
The rest of the album is also very good with tracks such as “Samantha”, “Venus”, “Poppaea”, giving an escape and some well refined gothic metal songs. “Bacchante” is probably my least favorite and its rightfully eclipsed by “Virago”, my second favorite of the album.
If you want to judge the quality of the album, submit it to the test of time and give it a listening session 20 years after the release. While in the 90s, some claimed the metal scene was deadbeat by grunge and alternative, it was only an appearance. It just needed to be searched, to be initiated by a friend or by a savvy record store to realize that underneath the visible, a whole new genre of metal was growing and morphing giving us some of the best sounds of the 90s. And Theatre of Tragedy was one of them.

[Metal/Melodic Death] Arch Enemy – Stigmata (20th Anniversary)

On May 5th 1998, Arch Enemy released their second album entitled “Stigmata”, with Johan Liiva on the vocals, Michael and Chris Amott behind the guitars, Martin Bengtsson on the bass and Daniel Erlandsson on the drums.

It follows the step of the first album “Black Earth” by keeping it heavy, fast-paced death metal but we also start to slightly different vibes premising the artistic direction of their next album “Wages of Sin”. It is a 12-songs album spanning a bit over 46 mins.

The album, although keeping a continuity with “Black Earth” also start to develop its own identity and gave signs of what the artistic direction the band will take in “Wages Of Sin”.
Indeed, we are navigating and alternative in the album between continuity in death metal (Beast Of Man, Dark of The Sun, Let The Killing Begin, Diva Satanica, Damnation’s Way) and innovative melodics (Stigmata, Sinsisters Mephisto, Hydra, Tears Of The Dead, Tears Of Destiny) and even a complete break from death with the introduction of power melodic ballads in tracks such as in “Vox Stellarum”, giving this sounds I call the “Michael Amott Midas Touch”.

But my favorite track that is coming out from the album in general is “Black Earth” with the the humming of the guitars at the beginning sounding like B-17 Flying Fortress.

Overall, the album is okay but listening back is missing this particular sounds that you have if you got into the band while Angela fronted the band. I am not fond of death in general and this can bias my overall experience, however I personally liked more the later iteration of the band with heavy infusion of melodics into their death.

 

 

[Sciences/Pharmacology] Ingestion versus injection explained to my cat

In the recent weeks, I have seen on several groups in which vaccines are discussed how people confuse injection and ingestion and use this term to explain the difference between getting exposed to a chemical from oral route versus vaccine injection route. Indeed, this oversimplification of terms resulted in an unexpected consequence similar to the classical sketch of the evolution of man:
consequences-of-evolution-631

Initially, this sketch was designed to represent the different iterations and species that resulted in the modern man (Homo sapiens). Yet, almost everybody understand this sketch as “Man is descending from apes!”. What was initially aimed to simplify a complex concept (that humans and modern primates are coming from a common ancestor and underwent several evolutionary steps) lead to an oversimplification resulting in a complete misunderstanding of the initial concept.
Same things happened with “ingestion versus injection” claim, putting into competition the “oral route” (per os or PO route) versus all other non-PO routes together (intravenous, intra-arterial, sub-cutaneous, intramuscular).
In this post, I will explain why this trope is wrong due to its oversimplification and explains a key element of pharmacokinetics: bioavailability.

1) Administration routes:
To simplify the concept I have drawn a sketch on my whiteboard (I know, I am not another Jean Monnet but it will make its job for us).

As you may know, we have several administration routes with one considered the gold standard: the intravenous route (IV route). IV route is what we refer in pharmacokinetics as a “vascular route”. This one is the preferred route, for many reasons:
1) You avoid first-pass metabolism
2) The whole amount of drugs injected is found in the circulation (100% bioavailability)
3) You can provide a single administration (IV bolus or shot), or a continuous infusion (constant IV infusion) if needed.

Now this administration has also several limitations and challenges, especially if you are a patient. You need specialized medical staff to install and remove an IV route.

In the other hand, we have other routes that we refer as “extravascular routes”. They are much less invasive, does not require a medical staff and can be self-administered by the patient. We have in these extravascular routes:
* Oral (per os or PO) route
* Sub-cutaneous (SC) route
* Intramuscular (IM) route

Unlike the IV route, these routes will experience a delayed delivery of the drug. In IV route, the maximal concentration is achieved almost immediately (C0). In other routes, it is delayed to a defined time (tmax) with a maximal concentration (Cmax) always lesser than the same dose administered by IV route.

Unknown

The reason why Cmax is always smaller than the C0 of IV route? The presence of an bioavailability.

2) Bioavailability:

Bioavailability is a ratio that determines how much of a drug administered via a non-IV route is getting into the bloodstream versus the amount of drug administered via IV route. By default, the IV route is considered as a 100% bioavailability. It is a complex equation that I will discuss in details here, but by default the bioavailability is always smaller than 100%. You can have variation in the bioavailability between IM, SC and PO routes but once the drug reached the bloodstream, these different routes behave exactly the same than the IV route.

Bioavailability is an important factor to consider because you cannot equate an IM, PO or SC administration to an IV route. You will have much lesser drug getting into the bloodstream by these routes versus an IV route. What always matter is how much drug is found in the bloodstream following administration.

This is also very important to consider when you have some drugs with a black box warnings. Some drugs are dosed to be correctly administered via IM or SC (e.g. Vitamin K), almost never by IV (in the case of Vitamin K, this is the black box warning). By injecting these formulation into IV, you will have an overdose effect.

In other cases scenario, some people are using studies performed in IV administration and then grossly extrapolate these into other routes without taking into account the bioavailability and the amount of drugs found in plasma after administration. This is the case of people trying to make claims made on aluminum, claiming wrongly that the aluminum injected with vaccines (IM, SC) will equate in terms of dose to the amount  injected via IV route (this is the case for people on kidney dialysis and being fed via IV bags 24/7). In the case of aluminum, both PO and IM/SC routes are very poor in delivering it into the bloodstream. We estimate it between 0.3% (PO) and 0.6% (IM/SC) of the total amount of aluminum injected to reach the circulation (https://www.ncbi.nlm.nih.gov/pubmed/11322172).

[Movies/Horror] Friday The 13th Series

Today is…..#HappyFriday13th! What a good day to celebrate one of the famous horror franchise, impersonated by the chubby guy with the hockey mask, Jason Voorhees. It is certainly not the first slasher movie by its appearance (the first slasher that has a wide audience was John Carpenter’s Halloween) but certaintly the most profitable.
Interestingly enough, Jason became an icon of the horror-pop culture, the boogeyman of the 80s and went beyond the genius work of Tom Savini (one of the best talented makeup artist in horror movies) to get a life by its own. According to Friday the 13th Wiki, Jason was the son of Pamela and Elias Voorhees, born on June 13, 1946 (Thursday). We know almost nothing about his father but we know his mother was showing an extreme attachment to her son (that get unfolded in both Friday the 13th Part I and II).
It seems the whole tragedy that will set Jason as a serial killer took place in Camp Crystal Lake in 1957, a summer camp owned by the Christy family and juxtaposing Crystal Lake, located in Cunningham County (likely a reference to Sean Cunningham), NJ. The drowning of Jason Voorhees under her mom’s watch was the event to set the franchise. Seeking revenge for her son’s death, Pamela killed two counselors having sex the next summer as she blamed his death on counselors having sex instead of watching her son. That resulted in the closing of the Camp Crystal Lake until 1979. Its reopening in 1979 by Steve Christy (son of the Christy’s family) sets up Camp Blood open for business.
I will go through the different movies of the franchise that are considered canon (and ignore the spin-off and others) and also some attempts of video games adaptation.

For your eyes only, all the Friday the 13th (I to X):
https://youtu.be/sLdy6yurbog

Friday the 13th (1980):
The first Friday the 13th, it is unique as the murderer is seen in plain sight and does not attract attention, unlike Jason Voorhees or Michael Myers. It is the only one starring Pamela Voorhees and not Jason as the main boogeyman, although Jason makes a cameo at the end. What it is probably the most interesting is the contribution of Henry Manfredini score giving this thrilling atmosphere and the now iconic “ki, ki, ki……ma, ma, ma……” (from “kill, mommy!” a sentence Pamela mentioning in her schizophrenic mind). What is also the most memorable in my opinion is the end sequence of the last survivor (she decapitated Pamela as a defense move), drifting on a canoe in the middle of the lake, with a soft and easy-listening song putting the viewer in a false sense of happy ending. Suddenly, from the lake comes Jason to try to drown her. White screen. Only to see that appears as a nightmare. Not only it confuses the reader (was it real? or just an hallucination) but cleverly opens up a possible second movie.

Friday the 13th, part 2 (1981):
The second movie takes place few years later after the first one. Alice, the only survivor of the first movie, is still fighting her demons. An impressive and oppressive figure comes in and kill her in her house, surely telling the audience someone is back with a vengeance. The scenario is fairly thin, just another excuse for some massacre and gore with the famous wheelchair victim. It is also the first time we discover Jason is the killer, hiding his ugly face with a potato bag. The last scene is fairly disturbing as one of the survivor found Jason’s shack and his mummified head and body. As a surviving reflex, she wears Pamela’s sweater and pose as his mother. The last sequence is in my opinion epic as it show one of the few times Jason without his mask. Less good than the first one but still okay.

Friday the 13th, Part 3 (1982):
You know you are running in trouble when you have almost a “Friday the 13th” movie every single year. What worse? When someone in the early 1980s thought that 3D movie was the future! (well you needed to wait another 20 years to get into the 3D movies in a sustainable manner). Just watching the opening sequence was enough to hear the screaming “exploitation” movie. However it worth its bag of pesos for finally Jason donning the hockey mask and ditching his potato bag. It is also posing as an unofficial final as Jason is presumably dead, hanging from a nose.

Friday the 13th, Final Chapter (1984):
My favorite. Not much by the quality of the movie but by the sentimental value. This was my first Friday the 13th movie, I was maybe 7 or 8 when I watch it, enough to get sermonized by  Daddy as I was afraid of going back in my room. The interesting thing about is having Jason coming back from the dead, as it takes immediately place right after Chapter 3. It also have the young Tommy Jarvis that will be a main antagonist in Chapter 5 and 6. It is kind of brutal and very dark. One of the best of the franchise in my opinion.

Friday the 13th, Part 5: A New Beginning (1985):
Another meh chapter. This time, Jason is dead, plain dead. But Tommy Jarvis is completely insane from the murder of his family by Jason. Since he is fighting his inner demon, seeing Jason everywhere. He is withdrawn and asocial, sent into a youth refuge for teenagers with social and behavioral issues (almost like Freddy III, sounds like troubled teenagers was the success recipe back then). Nothing much, except a reheated sauce in which a father (a paramedic) witness his son murdered by another patient and decide to don a Jason hockey mask to claim revenge a la Pamela Voorhees.

Friday the 13th, Part 6: Jason Lives (1986):
Hahaha! This one is one the best by its dark humor (from the title a la James Bond), its numerous reference (Frankenstein monster) and the execution style. This is my favorite. I will not spoil much about it. Watch it and enjoy the carnage!

Friday the 13th, Part 7: The New Blood (1988):
Probably new blood but nevertheless myasthenic, you can feel the franchise is peddling into some sauerkraut. It is nice for the killing but Jason facing a girl with telekinetic superpower? Come on…

Friday the 13th, Part 8: Jason Takes Manhattan (1989):
Don’t try to make any logic out of it, nothing makes sense in that one. How come a cruise ship can get out from a closed lake? Furthermore, sailing into Manhattan piers. No less! Come for the fun of seeing Jason wandering into Manhattan and the epic boxing scene!

Friday the 13th, Part 9: Jason Goes to Hell (1993):
This one is a bit weird as it start with Jason being ambushed by the FBI and blown into pieces. For some reason, Jason reincarnates by sharing body envelopes, transforming his victim into a killing machine (and reflecting as Jason). Interesting, as you learn about Jason’s relative and the particular ending.

Jason X (2001):
Imagine Jason slashing teenager in the 25th century. Yep! After being cryopreserved as a lifetime sentence (Demolition Man anyone?), his body get discovered by archeologists students, straight out a Star Trek movie. A Jason propelled into the 25th century knows that nothing beats his good old machete. That’s bring a very good laugh stock and killings (the liquid nitrogen killing was a unique one). Really watch it for the fun.

Now, videogame wise, there are few games. There is one I played on my cousin Commodore64 (Verboten! It was a bootleg copy of Friday the 13th game, because it was simply forbidden to sale in Germany). It was nice but a bit repeating. You have to identify Jason among the different counselor, as he is impersonating one of them (only revealing himself by killing others). You know he is for a killing spree when you have the particular music coming…..

Another video game port was the infamous NES port by LJN, a pile of BS non-sense as reviewed by the AngryVideogameNerd. Oh my God, that was some awful game!

Not directly Friday the 13th but you should give a try to the Splatterhouse series by Namco, with the hero being some kind of Jason fighting monster.Dammit I sold my Splatterhouse 2 SEGA Genesis copy a long time ago!:

Now there is a multiplayer game coming soon that looks very exciting, somewhere in the vein of the original C64 but with one player playing Jason and others counselors trying to set booby-traps and survive his assaults.
https://youtu.be/q9jUJRrMQrM

[Metal/Heavy] Iron Maiden – Seventh Son of A Seventh Son (30th Anniversary)

Today marks the 30th anniversary release of “Seventh Son of a Seventh Son” by Iron Maiden. This album has a special place in my heart, because this is the album that introduced me to Iron Maiden (via the song eponym to the album).
I still remember listening to this album as a friend of my brother came in and put that CD into the Hi-Fi system. It was some lovely tunes to my ears, allowing me to get over the stereotype of Eddie (as a teen) and indeed appreciate something different from the hard rock I used to listen while in middle school and discover the realm of The New Wave of British Heavy Metal, made of wonderful melodic riffs of Adrian Smith and Steve Harris and storytelling lyrics narrated by Bruce Dickinson.
It is also interesting to note that it was the introduction of keyboards into Iron Maiden and according to some excerpts in Wikipedia, Bruce attributed the decreased sales on the US Market on the presence of these keyboard elements. However, he also questioned and criticized some comments that the album was sounding as “European-style Iron Maiden”, arguing that there is no a European or American-style Iron Maiden. It is interesting because reading it today explains while there is such a rift in metal style between the US and Europe (with me having hard time to find decent band in the former, while having most of my collection coming from the latter).
It also support my opinion that US metal listeners have a fond for simple but brutal riffs (without keyboards), while European metal listeners have a certain attraction to complex instrumentations and the presence of keyboards.
The album is an 8 track album totaling about 40 minutes. We get into it very progressively with “Moonchild”, followed by “Infinite Dreams” and by “Can I play with Madness”. “Can I play with Madness” is one of the three tracks that got a release as a single and an official music video in the glory age of MTV (when MTV was about Music TV, just that).

But things start to get very serious with “The Evil Things Man Can Do”, one of my top 10 Iron Maiden songs. A song that want to make you raise your arm and yell “Up The Irons”

But the piece of resistance, the paroxysm in the album is only coming with the song “Seventh Son of a Seventh Son” in which we get the most of the keyboard element and this was my first song that I ever listened from Iron Maiden.
After being introduced by the riffs of Adrian and the keyboards comes Bruce narrating about the story of the Seven Sons.
Here they stand brothers them allAll the sons divided they’d fallHere await the birth of the sonThe seventh, the heavenly, the chosen one.
Followed by the “Ooooooooooohhhhhhhh” of Bruce. Oh my, this is such a musical orgasm to listen, with all the goosebumps and the piloerections on my arms!
Here the birth from an unbroken line/ Born the healer the seventh, his time/ Unknowingly blessed and as his life unfolds/ Slowly unveiling the power he holds“.
All followed by the interlude guitar solo with Adrian and Steve that gives this depth and complexity, interrupted by Bruce monologue “Today is born the seventh one/Born of woman the seventh son/And he in turn of a seventh son/He has the power to heal/He has the gift of the second sight/He is the chosen one/So it shall be written/So it shall be done“. Listening to this beauty while you are 14 is priceless!
Things cool down with the seventh and eight tracks “The Prophecy” and “Only The Good Die Young”.
After 30 years, this is an album that still stand strong, and would definitely recommend as a primer for anyone that want to get into Iron Maiden. Up the Irons!

[Metal/Symphonic] Whyzdom – As Time Turns To Dust (85%)

Whyzdom (probably the best French Symphonic Metal band IMO), after three years of waiting, released their fourth album “As Time Turns To Dust”. So, how does this album stands and compare to their previous releases? I would say unique and similar at the same time (for some reasons it reminded at times of their second album “Blind?”, propelled by Vince Leff at the helm and by Marie McLeod at the front.
We have in hand a 9-tracks song with 58 minutes of pure enchantment Whyzdom-style. It all starts with “Armour of Dust”, introducing us in a Hans Zimmer’s style “a la Dark Knight” followed by some classic Whyzdom. The second track, “Armageddon” is surprisingly not really my favorite despite being heavy. I don’t know why I dont really click on that one. “Fly Away”, is a good track but still missing something to make me all excited about. “The Page” is probably my favorite starting with a guitar solo and Marie, going crescendo and becoming more and more complex until you reach a paroxysmal euphoria. Thats the kind of auditive cues that make you limbic system overstimulated. “Follow Your Heart”, the 5th track of the album, has this Epica feeling that is making it very attractive. “Angel of Tears” is a good one, starting with the Celtic vibes and very dynamic. “Free As a Bird” is for some reasons reminding me of “Cassandra”. “The Mistchild” has this feeling of proximity of “Blind?”.  The last track, “Dust We Are”, is good but I have experienced more enjoyment in tracks of their previous album.
Overall the album is good, but I feel there was something missing. I really worked hard on this album by listening at least five times before writing my critique. I did not feel the shock and awe that I have with “Tears of a Hopeless God”, I don’t why. The album is good, but it was not giving me the thrills that would make it “an amazing experience”. Maybe it is just me becoming an old schmuck.
Anyway, the album is a good one and if you are looking for some new sounds in the Symphonic that is not from the four Valkyries of the Symphonic Metal, you should definitely try Whyzdom and feel what the French touch sounds like when they tamper with Symphonic Metal, something unique.