Brenna's Testimony - Questions

Dr Brenna is an expert in the field of IRMS and has had many papers published in this area. Some have been referenced in Dr Meier-Augenstein's own papers. However, some unusual anomalies appeared during the course of the hearing. Anomalies in the form of differences of opinion between Brenna and Meier-Augenstein over the answer to relatively straightforward questions (the effect on o/oo values for overlapping peaks).

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This naturally leads one down the path of looking for other anomalies. After all, their difference of opinion over the effect of overlapping peaks is one which forces an observer to believe either one person or the other. They cannot both be correct. Their opinions represent the compliment of each other.

Brenna testified that during IRMS processing of the B samples, the process was automatic and that the only intervention by the technicians was for what he referred to as "quality control" purposes. Clearly, the question had been asked to determine whether the results could have been influenced by the technicians (no doubt in light of the fact that they knew which were Floyd's samples and which were the blanks). Brenna testified that the process had been automatic, not manual. Thus implying that the they could not have influenced the results. That effectively removed any question of bias during this process and, in the eyes of the arbitration panel, validated all of those results.

Moving to page 169 of the official transcript, Brenna describes the quality control actions carried out by the technicians, as observed by himself during the official testing of all of Landis' B samples. His testimony describes how the LNDD technicians, following their internal SOP, determine for themselves where the peak of interest is deemed to start and end. This is done by observing the 45/44 ratio plot and the value of the background o/oo at the start of the peak (more on this later). The first observation one would make at this point is that, clearly, selection of the integration limits are not done automatically. So which aspect of this process was automatic ?. Defining where the peak integration begins and ends also defines the background removal (everything below a straight line fit between the intersection of the integration limits and the peak). So in defining the integration limits, they are defining what is to be considered background. So which aspect of this process was automatic ?. All of the decisions which influence the computed o/oo value of the peak of interest have been taken by the lab technician. The only thing they didn't do was the number crunching necessary to evaluate their decisions. We'll leave this as an open question. Was this an automatic process ?. Brenna testified that it was.

The SOP for determining the peak start and stop times is described in detail in Brenna's testimony. The o/oo value of the background is determined from the 45/44 ratio plot at the start of the peak. The 45/44 plot is then scanned to determine where the same 45/44 value reoccurs at what appears to be the end of the peak. This is then deemed to be the end of the integration interval. A sanity check is performed by checking the defined interval on th 44 plot and any gross errors will be observed there. However, the "integration for Idiots" series highlighted that gross errors are not required to skew the results.

The presence of interference between peaks distorts the true 45/44 ratio plot for a peak. This can lead to shifts in when the 45/44 plot appears to return to the baseline. So, by following the LNDD SOP (in the presence of the sort of interference between peaks evident in Floyd's F3 plots), inaccurate results become more than just theorhetical possibilities. They become hard to avoid realities.

The most obvious question was how unbiased was Brenna's testimony ?

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Friday Roundup

In case you have missed it be sure to read Floyd Landis' op-ed piece,"Dopers Must be Stoned" (or so says Patrice Brunet) published here on Monday.

Special Coverage


WADA Watch has been issuing a series of fascinating reports from the Madrid WADA conference that we just noticed -- because he mailed us, saying, "Apartheid means self-employed bloggers, and those Countries or Federations that haven't paid their annual dues, are relegated to a beautiful basement movie-theater-sized room,"

Richard Young, he of the Floyd Landis 'prosecution team', from the USA, is now addressing the room, about changes in the WADA Code.

I wonder which among us knew, that he had these two roles?

News
The VeloNews provides a podcast containing a report by correspondent Charles Pelkey who is attending the the 2007 WADA anti- doping summit in Madrid.

Azstarnet.com previews tomorrow's El Tour de Tucson and Floyd Landis has been invited to attend as he did last year, though no word yet on whether he will. Someone who will be there is Greg LeMond, things could get interesting if both attend.

The Miami Herald notes that it was lying to Federal officials, and not cheating, that ultimately doomed Barry Bonds. The Baltimore Sun carries the nuts and bolts of the story with the obligatory Floyd Landis reference.


The CyclingNews, in its first update of the day, reports that fears of the weakened US dollar may hurt WADA labs in their quest for cutting edge anti-doping research, and Jaime Lissavetzky, the Spanish Secretary of State for Sport, wants more respect from Pat McQuaid. The CyclingNews now reports that Patrik Sinkewitz received a one years suspension from the UCI.

The CyclingNews Friday Mailbag is full of letters concerning the various doping stories in cycling from of the past week.

USA Today reports that Europeans at the WADA anti-doping summit in Madrid are asking Dick Pound to stay on temporarily as WADA president as they are not satisfied with sole candidate for the postion John Fahey. And in a related story WADA may be looking for commercial sponsorships to alleviate the drop in funding due to the weakened US dollar.

AFP updates an older story about AFLD wanting to make sure Landis doesn't sneak into the Tour despite a ban, if ASO runs it without UCI sanction. As if ASO would allow a team with Landis to start while banned.

Blogs
A Bag full of Health and Politics wants to know why Barry Bonds, instead of Floyd Landis, is the one who may go to jail for perjury. He states categorically that Landis lied, how does he know that? Not to mention the fact that Landis never testified under to oath to a grand jury, if you lie that's how you get charged with perjury.

Midnight Marauder seems "legally confused" in thinking that Floyd Landis might be a "cell mate" to Barry Bonds.

Running Down a Dream says that after years of being disappointed by tainted athletic accomplishments we are jaded and Barry Bonds is just the latest name on that long list which includes Floyd Landis.

FanNation presents lines of defense for Bonds, including Hamilton's twin, and Floyd's "blame the French." Snark o' the day candidate.

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Thursday Roundup

In case you have missed it with all that has been posted on TBV the past few days be sure to read Floyd Landis' op-ed piece,"Dopers Must be Stoned" (or so says Patrice Brunet) published here on Monday.

News
The CyclingNews notes the opening today of the WADA Anti-Doping Summit in Madrid, Spain where Dick Pound stated that doping is not only the greatest threat to sports that has ever existed, but also that it is a threat to public health in general:

Outgoing WADA President Dick Pound drew a connection between doping and endangered public health. "Doping is without doubt the greatest threat ethical sport has ever known and has become so pervasive that it places public health at grave risk. It is incumbent upon the Sport Movement and Governments of the world to continue to bolster efforts to battle the scourge of doping ... by approving refinements to the World Anti-Doping Code and by discussing emerging trends and strategies for continued progress.

Pound also sets his sights on Operation Puerto, and rightly wonders why he has only received information from it concerning cyclists:

"It just doesn't make sense that only cyclists are dopers," Pound, who believes the Puerto case goes beyond just cycling, to the Associated Press. "The only documents given to me are related to cyclists. That is quite different to saying that all of the documents don't include other sports."

In a PM update the CN tells us that Michael Rasmussen is suing his old team, Rabobank, and that if he is suspended for two years by the UCI his cycling life is over.

ESPN outlines the key changes that would occur within the WADA code, if approved, at the ongoing anti-doping summit in Madrid. Here are a few of the salient points:

Athletes to face a four-year suspension [up from two years] for a first doping offense in "aggravated" cases. This includes athletes involved in a larger doping scheme; using prohibited substances on multiple occasions; if the athlete enjoys the effect of the prohibited substance for a period longer than the term of ineligibility; or for impeding the investigation of an anti-doping offense.

Athletes to be considered guilty of a doping violation if they accumulate a combination of three missed tests and/or fail to provide information of their whereabouts within an 18-month period.

Athletes to get reduced bans if they admit to doping; assist officials in catching other drug cheats; lead investigators to a larger doping scheme; or prove the prohibited substance was not intended to enhance performance.

Testing time between "A" and "B" samples to be reduced; athletes to be provisionally suspended after a positive "A" sample.

WADA can appeal a sanction or non-sanction by national anti-doping organizations directly to the Court of Arbitration of Sport.

The VeloNews contains numerous "Poundisms" coming from the anti-doping summit in Madrid this week. Among the most memorable may be this comment on seeking the leadership of the CAS:

Pound said he's interested in the soon-to-be-open spot as head of the International Court of Arbitration for Sport.

"I'm available," said Pound, who is both an accountant and attorney. "Listen, it would be the first time in 30 years that the IOC has given me a job that I actually understand."

Many would unfortunately have to agree with the above.


The IHT further notes the retirement of Dick Pound and his "dirty job well dome", and makes the point that he all too often refrained restraint in favor of headline making quotes.

The Citizen.co.za quotes two legal experts in sports litigations who say that the newly proposed WADA code, in which penalties for some doping offenses would be increased, does not effect the athlete's human rights. It does not mention the proposal to eliminate the "B" sample testing procedure. The piece is accompanied by an old photo of a "drug tainted" Floyd Landis which in itself seems to illustrate what can happen to some of an accused athlete's basic human rights when rules are violated within the WADA code.

The BBC has an article by Victor Conte, the BALCO founder, on things he'd want done to clean up sport. His big thing is out-of-competition tests. There should be more worldwide of highly ranked athletes, done by WADA directly and not national federations, and two missed tests should be considered a positive.


Blogs
Rant discusses the Rabobank/Rasmussen independent report issued earlier this week.

CFA talks about Dick Pound and OP, and also throws a challenge to former Landis trainer Allen Lim who now works with the Slipstream/Chipotle team. CFA snarks that Lim should obviously know more about Floyd Landis' possible doping than he had said and wants journalists to go after Lim to come clean, as it were.

Blakely says that those who think that testosterone is useless when abused in the manner Floyd Landis is alleged to have used it are just plain wrong.

Adam says "so long Dick".

Balderdash thinks one of Dick Pound's infamous quotes from the past year is "funny", many would disagree.

Science FictionTwin gives us "virtual Floyd Landis". As Gary says, it's not what you think.

WADAWatch promises more from the anti-doping summit, soon.

Did Stevil Kinevil have a close encounter with Floyd Landis, or was it Memmorex? An intriguingly confusing blog begs these and other metaphysical questions.

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Wednesday Roundup

In case you have missed it with all that has been posted on TBV the past few days be sure to read Floyd Landis' op-ed piece,"Dopers Must be Stoned" (or so says Patrice Brunet) published here on Monday.

News
The IHT says that just because Dick Pound is leaving WADA as its president we shouldn't expect him to quietly slip away into retirement. As Pound presides over the Madrid anti-doping summit, which begins tomorrow, he leaves behind a legacy which at its very least brought greater exposure to the wide spread problem of doping in sports. But, his tenure as head of WADA was consistently controversial and not universally appreciated:

Former International Cycling Union head Hein Verbruggen called Pound's leadership of WADA a "catastrophe."

"He says that to run that agency it's necessary to be controversial, but I didn't think you needed that and I don't think the stakeholders expected that," Verbruggen said. "His style meant that the public believed every athlete was a suspected athlete. All he does is accuses. ... Insulting people who don't fight the battle against doping is wrong, especially without proof."

Pound also comments on the fight over his successor and his desire to become president of the CAS.


Azstarnet.com promotes El Tour de Tucson and apparently feels it necessary to insult Floyd Landis while doing so.

The CyclingNews has a bit more in today's early update about Patrik Sinkewitz's deal with prosecutors which prevented his sponsors from pursuing him legally, and Michael Rasmussen will finally meet today with the UCI in Switzerland to discuss the circumstances under which he was fired from Rabobank and kicked out of last summer's Tour de France.

The NYTimes posts a piece about Jonanthan Vaughters' Slipstream-Chipotle team with the emphasis of the story on confessed doper David Millar. It briefly mentions Floyd Landis along with other Tour de France scandals to point out how badly the sport of cycling needs a "clean" team.

WTVO/WQRF in Rockford reports that Illinois high school athletes may be tested starting next year for PED use.

Blogs
Rant feels it very ill advised for WADA to eliminate the "B" sample testing it has proposed to do with revisions in its code to be discussed at the doping summit in Madrid this week. He also says that IF WADA really wants to do something it should assure the people who careers as athletes might depend on their tests to improve the quality of the work they do.

Racejunkie felt the Floyd Landis op-ed piece was right on target with its call for due process in the pursuit of "justice" within the ADAs. RJ also wonders about the quality of the writing over at the NY Times as he read the cycling article cited above about "St." David Millar's experiences in jail.

Phantom Refections likes what he sees in the 2008 Amgen Tour of California route, he only wishes Floyd Landis could race it too.

Lugo writes a most confusing opinion piece on Floyd Landis and fellow "cyclist" Justin Gatlin.

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An emailer looks at peak identification

The same emailer who looked at chromatograms with us a few weeks ago has looked at the peak identification question, and finds himself unsatisfied with LNDD's eyeballs.

UPDATE: Retracted due to error. The author concludes:

Yes, nevermind. I thought I had found the simple, but overlooked. It is time for me to shut up and listen.

We leave it around as a reminder to be careful.

Mail #1

If you like, pass on these simple spreadsheets and graphs. It is my understanding that the log of the retention time should be compared on an isothermal GC.

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[Ex 84 sample 85424 spreadsheet; and Ex 86 sample 85428 spreadsheet]

'424 matching peaks 10 and 11

'424 matching peaks 11 and 12

'428 matching peak 18 and 19

'428 matching peak 19 and 20

I think these graphs should show a straight line fit through the best peak assignments. If so, it appears that the LNDD peak assignments may be more likely wrong than correct.

Of course, we have already shown a lack of consistency in peak heights between the two machines, and peaks moving around relative to each other.

Time didn't permit further investigation across other samples, but please let me know if this is useful.


Mail #2

Look in Ex84 (References to handwritten page numbers)

LNDD 707

1. Page 70 [LNDD 707] identifies the compounds in Mix Cal Acetate 001C to include 5b Androstanol and 5a Androstanol AC

LNDD 720

LNDD 721

2. Page 83 [LNDD720] (and accompanying GC chart) [LNDD 721] identifies retention times on the GC/IRMS instrument at 1246.9 and 1319.7, which should correspond to 5b and 5a, respectively.

LNDD 705

3. Page 68 [LNDD 705] identifies the retention times on F3. The peak at 1265.6 is ignored. Peaks at 1329.1 and 1359.1 appear to be identified as 5b and 5a, respectively.

4. This is very convincing evidence that the peaks are mis-identified. Notice that if the F3 peaks at 1265.6 and 1329.1 are the real 5b, and 5a peaks respectively, the retention time more closely matches the cal-acetate than does the F3 peaks LNDD appears to call 5b and 5a at 1329 and 1359. Also notice the similarity in the difference between the 5b and 5a peaks.

Thus, if these observations are correct, and apply to all samples, this is very convincing evidence that Landis is truly innocent.

This observation is consistent with your earlier overlays related to the Retention Times discussions, and my graphs from yesterday.

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A gun, not necessarily smoking

In the exhibits to a complaint made to the Panel, "Violations of Panels Orders", USADA included a number of pages of correspondence between WADA and LNDD we'd not seen before. Apparently, LNDD was under some "corrective action" requirements over various problems. Skip on down to Exhibit C on page 13...

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We start on page 14 with a letter to LNDD on September 1st -- before the ADRB has considered the Landis case at all.

WADA wants to know about contamination of blanks (as shown in the whistleblower documents).









Page 15 contains the first LNDD answer, on 8-Sep, saying they "reconsidered" the resuls because the metabolite monitored was different than that in the confirmation step.













Page 16 continues, saying the reconsideration looked for the contamination, and shucks, they found some, so they decided to re-analyze the sample.

They thought they might be contaminated because the blanks also showed positive.









page 17 is a letter from WADA on 18-Sep, asking aabout the data review process they went before sending out the A finding.














On page 18, LNDD gets new letterhead, and is now AFLD, lowercase.

On 25-Oct they offer more documentation, but don't exactly say what QC they conducted before sending out an erroneous A sample report.









page 19, on 9-Dec, WADA gets around to asking LNDD why the couldn't have checked this before sending a result out?

Also, what about interference?











page 20 adds, by the way, here's a form you should get used to filling out when you make a mistake.














page 21, on 15-Dec, LNDD answers and says here is your form and what we've done.

We aren't given a copy of that material by USADA. Whatever corrections in policy for A-sample QC before delivering a report are not stated or provided to the Panel or Landis in this exhibit.






page 22 shows that on 15-Mar, WADA gets the report, but doesn't seem to believe it. They want evidence the corrective action has been taken.











page 23, on 3-April, LNDD says it has added new steps to their laboratory documents.

These steps are not included in the exhibit package.












Notably missing from the pages provided by USADA in this exhibit are the details of the corrective action sheets, and a final confirmation that WADA considers the matter closed.

We note our long-running theory is that proper examination of the A sample before it was reported may have resulted in additional checks that would not have resulted in a positive report. But once it was out, there was politically no way to back down because of the publicity. From a post almost exactly a year ago:

My opinion about the the whole thing is that circumstances are far more mundane than a grand conspiracy. I've always leaned towards the "he didn't do anything wrong" position, and nothing has moved me from that posture. This may mark me as naive, but so be it.

It seems most likely to me to multiply simple human error by bureucratic entrenchment. Something wrong happened at the lab that wasn't recognized, and an initial positive was made. This rapidly escalated to a point where the heavy rhetoric was employed. It became impossible for any other explanation to be considered by the officialdom, and the same problems were experienced to get the expected results in the B sample. After more spouting, calmer heads prevail in some organizations, but USADA is saddled with a charged case it feels it cannot lose for all kinds of political reasons. This leads them to progressively harden their position into near absurdity.

We have here evidence that WADA itself was concerned by the lack of appropriate review by LNDD before A sample results were distributed, and this matter was not closed even as of early 2007.

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Primary Document Links

While looking around for documents on the lost mass-spec data, we decided to put together links for places where primary documents are located.

All posts tagged with primary document can be found with a simple search that is always up to date. Other pointers in the continuation.

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Some of these have their own indexes.

November 07 document dump.

September 07 decision documents.

Official Hearing Transcripts.

Partial Hearing Exhibits.

Landis Opening Statement Slides.

Hearing Monday Documents. Procedural orders 1, 2, 3, 4, 5, interlocutory awards.

Hearing Schedule, May 11, 2007

Landis Statement from Press Conference May 10 2007.

Henson Statement, from May 10, 2007.

Decision w/o Campbell and Dissent, May 8th 2007.

FFF White Paper on the Gag Rule, May 5, 2007.

Landis Press Release about deleted files, April 29, 2007.

Whistleblower Documents, April 26, 2007.

Landis Press Conference, April 23rd 2007.

FFF Statement about access denied, April 23, 2007.

FFF Statement about USADA discovery request, April 16, 2007.

Landis Statement on USADA discovery request, April 11, 2007

USADA Document request of April 3, 2007.

Landis Statement about alternate B sample testing, April 12, 2007.

First Arbitration Decision (Interlocutory award #1).

No Documents for You! (series, Nov 2006)

The LDP, USADA 001-370. October 2006.

ADRB Filing, October 2006.

Final Ferret, UCI announces Positive B, August 2006.

Ferret II, Parts of the LDP, Octber 1, 2006.

Ferret I, LDP Page showing 3 tests, one detecting morphia, Sep 30, 2006.

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Probabilities

by Ali and TBV

After thinking about the many metabolites of methyl' and dexa', we asked ourselves how likely was it that they might elute in regions that could cause problems.

The familiar USADA 349, Landis B sample F3

We poked at this two ways, a Monte Carlo simulation, and analytically. We assumed 19 metabolites that are free to co-elute with each other, in the 882 seconds between 800 and 1682 seconds, with a uniform distribution. This encompasses the IS to the bumps past the ostensible Pdiols.

The Monte Carlo method made a sheet of 19 columns and 1000 rows, and placed a random value in the range in each cell. The result was around a 0.5 probability of one co-eluting between the start of the 5bA and the end of the 5aA, being the 34 seconds between 1326 and 1360.

The analytic approach yielded:

Probability of peak NOT occurring in range of interest is

(882-34)/882.

Probability of all 19 peaks NOT occurring in range of interest

((882-34)/882)^19.

So the probability of one or more occuring in range of interest is

1-((882-34)/882)^19 = 0.526

In English, there seems to be a 52% chance there is co-elution of at least one of the metabolites of the TUE'd medication showing up in a region likely to conflict with the measured peaks.

These are first guesses, but more or less agree. We appreciate correction and feedback.

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Tuesday Roundup

News
The LA Times' Michael Hiltzik writes about this week's WADA anti-doping summit in Madrid where the doping agency faces some difficulties despite some "victories" this year including the arbitration decision that went against Floyd Landis. The crux of the conference will be to update and implement "The World Anti-Doping Code":

The new draft, which is to go into effect in 2009, is almost certain to be approved. It will stiffen the penalties for several categories of drug use and water down a key procedural protection for athletes -- the requirement that positive findings from an athlete's primary, or A, sample be confirmed by tests on a backup, or B, sample taken at the same time. Several cases against prominent athletes, including Jones and Kenyan distance runner Bernard Lagat, had to be dropped after their B test results were negative or inconclusive. Under the new rules, a B test would not be needed to confirm a doping finding if the prosecuting agency "provides a satisfactory explanation" for the lack of confirmation. "That's a huge change that the anti-doping agencies have always wanted," said Howard Jacobs, a Los Angeles-based athletes' lawyer. "The B test is one of the very few safeguards the athlete has, and now they want to do away with it." Another proposed change would lengthen the possible suspensions imposed on athletes accused of doping. For a first offense, athletes found with even a trace of a banned substance in their sample are currently subject to a two-year ban from competition. (A subsequent violation carries a lifetime ban.)

The attempt to toughen penalties and tighten procedures comes at a time when WADA took some lumps at the Landis/USADA hearings where criticism of the LNDD, a WADA sanctioned lab, was part of the Landis defense. But, the ugliest part of the conference may actually involve the selection of retiring president Dick Pound's replacement, stay tuned.

The CyclingNews provides more details on the Michael Rasmussen story this morning with Rasmussen's response to the investigation into his dismissal last summer due out tomorrow. Also it appears the UCI's Pat McQuaid has some issues to deal with himself in Belgium today as he faces calls from European event organizers that he respect the traditions of cycling there, or they may take their marbles and play somewhere else. In the PM update the CN provides more details from the investigation into the Michael Rasmussen saga from last summer. It also appears that Danilo DiLuca will not bother to appeal his three month suspension by CONI to the CAS.

The NYTimes this morning reports that the "Mitchell Report" on steroid use in baseball is due to be published very soon, and all anyone cares about is naming the names. And from the Health Section better living, or performing, through chemistry is discussed.

The VeloNews posts a blurb for the appearance of Genevieve Jeanson, the Canadian cyclist who admitted to using EPO, on Bicycleradio.com this evening.

Reuters notes that few tears will be shed over Mr. Pound's departure from WADA, and cites Floyd Landis as one particularly dry-eyed observer.

ESPN reports that Patrik Sinkewitz's cooperation with German authorities has paid off. He will face a substantial fine of five figures, but will not be criminally prosecuted

The Boulder Report reads like a Floyd Landis old home week entry, without Floyd Landis. Joe Lindsey writes about Dave Zabriskie's wind tunnel testing done with the scientific assistance of Allen Lim. Further down in the piece the PowerTap/Zipp collaboration is expounded on.

Blogs
Rant catches us up on actual Floyd Landis news including comments on the selection and naming of the CAS panel which will hear the Landis appeal as well as Floyd's op-ed piece published yesterday on TBV.

Derwood remembers a seemingly long ago epic day, and he has photos to remember it by.

Dugard thinks that endurance sports need to reclaim their relevance, and that athletes in more popular sports genres who cheat need to be treated by the press just as badly as they treated Floyd Landis.

Racejunkie looks first at Rasmussen, and crystallizes our own thoughts on hearing the "independent" conclusions:

Rabobank Lied, and It's Still All Rasmussen's Fault

Doesn't that work out well for the backer of the report?

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Now chasing specificity and methylprednisolone: Mister Idiot, himself

In a comment, the estimable Mr. Idiot writes the following, and we cede the floor to this discussion:

In simplest terms, TbV's and Ali's work has shown that there is some possibility that something, or somethings, other than the right things, have found their way into the peaks of interest. This post is about what that could be.

Exhibit 106 of Floyd's recent document dump gave us some information we were long interested in - the exact substance injected into Floyd's hip on July 8, 2006 (and May 5, 2006 by the way). It was two glucocorticoids called dexamethasone (hereafter dexa') and methylprednisolone (hereafter methyl'). Glucocorticoids (a.k.a. corticosteroids) are a class of non-sex hormone related steroids, but they are still chemically very similar to testosterone.

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Both of these substances are banned by WADA, but were covered by a Therapeutic Use Exemption for Floyd. They are both only exogenous. Unlike testosterone your body doesn't make any of this stuff.

Like testosterone, dexa' and methyl' both are metabolized by your body and broken down into other compounds. When you have it injected "intra-articularly" (into a joint) these metabolites can come out in your urine for a long time (weeks at least).

Dexa' comes out in your urine partly intact, and also as four different metabolites. Methyl' comes out partly as itself, and also as sixteen different metabolites.

So, the obvious question is, "Did any of these metabolites co-elute to any degree with the 5aA (or 5bA)?" In other words, “Do any of these metabolites show up as the little peaks, and shoulders, and possible hidden elutes in our peaks of interest?” And if you are an astute Floyd junkie, you will also wonder "If any of these metabolites did co-elute, could that have lead to a strongly negative CIR?" (although as we have seen, the negativity could be increased by a partial co-elute even if the substance was not highly negative, depending on the starts and stops of integration).

So, “Did any of these metabolites co-elute to any degree with 5aA (or 5bA)?” The answer is “maybe.”

Unfortunately, the only way to tell for sure is to have the complete mass spectra data of the relevant peaks. That information is gone.

So, what are we left with? Well, what we would like to have is some evidence that at least one of those 20 metabolites has a habit of eluting at least somewhere near the metabolites of testosterone. The problem is that when something elutes in a GC/MS is not really predictable. In different chromatographic conditions, stuff elutes at different times. And it is particularly hard to predict the retention time when dealing with glucocorticoids like dexa’ and methyl’, because they are highly temperature sensitive, so small changes in the conditions will strongly affect the elution time.

I have not found a single chromatogram available on the internet that has dexa’ or methyl’ along with testosterone (or their metabolites) shown on the same chromatogram.

A further complication is that testing for glucocorticoids is usually done with liquid chromatography / mass spectrometry (LC/MS), rather than GC/MS. This is for several reasons. First GC/MS (at least the way LNDD does it) involves certain steps to prepare the samples to be analyzed. One of the steps is acylation. I don’t get the details of the chemistry, but the effect is if the compound has any hydroxyl (Oxygen and Hydrogen together) groups, it ends up lowering the CIR of the compound. Many of the methyl’ metabolites have numerous hydroxyl groups, so the resulting compound could have seriously negative CIRs.

Another reason LC/MS is used is that glucocorticoids are hard to turn into gases (they have low volatility) and they are very temperature sensitive, making consistent results in GC/MS difficult to achieve. That superiority of LC/MS for analyzing glucocorticoids may be why they aren’t normally shown on the same chromatogram.

So, the summary of all that is that it does not really seem possible to show ahead of time whether these two compounds, dexa’ and methyl’, or and their 20 metabolites, would elute with 5aA or anything else. Too much depends on the particular circumstances of the particular set-up of the particular GC/MS machine using a particular process.

Now, most of you reading this remember the great discussion between Larry and m about whether the demands of TD2003IDCR were met. The most generous take on all that is that LNDD did met TD2003IDCR using a “relaxed relative retention time” standard. The 1% standard stated in the document would need to be relaxed to about 6%.

What that means is that any of these dexa’ and methyl’ metabolites that were within 6% of the peak of interest in the GC/MS have to be considered as possible co-elutes in the IRMS (there may be even more movement of substances than that between the GC/MS and the IRMS, but that’s a conservative, but big enough window).

Remember we are talking two main compounds and 20 metabolites. It seems reasonable to conclude that one or more of them fall within 6% of the 5aA peak in the GC/MS. Looking at the chromatogram, there are some possibilities there. Any one of those could have negatively skewed the CIR in the IRMS.

Of course, the complete mass spectra data could have made all of this moot, because it could have shown the purity of the peaks in the GC/MS and identified everything around it. So we would have known there were possible problems. But, alas, that information was erased.

In the end, this is all about specificity, the way LNDD assures the purity of its peaks. In short, they don't, because they don't have the mass spec data.

And with dexamethasone and methylprednisolone we have compounds that could have caused contamination / interference, and there seems to be no way to show they didn't, and no way to show they did.

So, my guess is that means a big fight over the meaning of the legal requirements of ISL 5.4.4.2.1, and perhaps other documents. The chemistry leads right back to the law. But I won’t go into that right now.

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Dopers Must be Stoned (Or so says Patrice Brunet)

In the first of what we hope to be occasional opinion pieces, Floyd Landis has provided the following observations on Patrice Brunet's recent suggestions in Pedal magazine to handle more anti-doping enforcement through criminal mechanisms of the state.

Dopers Must be Stoned
(Or so says Patrice Brunet)

by Floyd Landis

In the civilized world, governments exist to enforce laws, and they do so to preserve the rights of law-abiding citizens. But here is the dilemma: giving the government decisive power means they must be held to the same rules as the people. This prevents the undue punishment of an innocent, law-abiding citizen at the hands of a biased judge.

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For this reason I agree whole-heartedly with Mr. Patrice Brunet when he states that doping in sports should be enforced by the federal government. Certainly, in my case against the US Anti Doping Agency, the prosecution (USADA) would have been held to a much higher standard.

Were it a federal case, I would have been provided with all relevant documentation and lab protocol within days, rather than spending one million dollars in legal fees and ten months just to acquire the evidence against me. After all, in a federal case, when the prosecution refuses to produce evidence that they purport exists, they are ordered to do so or the case is dismissed. Unfortunately, in the case of the WADA rules, under which Mr. Brunet operates, the "judge" has no authority to order either the prosecution or the defendant to do anything. Moreover, the "judge" is bound by no accountability, and in extreme cases, as in mine, there can be motions filed by the defendant which, after the decision is rendered, are never ruled upon.

Were it a federal case, a jury of my peers would be deciding the case rather than a panel of WADA employees who, between IOC galas in Beijing, decide the fate of unprotected athletes. Certainly, Mr. Brunet would agree that the Olympics are a monopoly and that those who wish to participate in the Olympics are in no position to dispute the rules, written by the International Olympic Committee, which mandate an arbitration process rather than a federal one. He cannot have both, Mr. Brunet must decide if he'd like to continue to eat the free shrimp at the IOC events or allow the federal government to deal with these things.

Mr. Brunet suggests Canada should use the same system as France, which would mean two different hearings for the same offense. In my case, I was expected to appear and defend myself at one hearing against USASA, over which Mr. Brunet presided, and a second in France, where the federal law mandates a separate hearing.

This is clearly not how WADA intended things to work. WADA’s very first priority is “working for proper adjudication of results” which they define as a hearing in the country of origin of the athlete with the right to appeal to a further arbitration under the Olympic committee. My hearing in France and what Mr. Brunet is suggesting makes no sense with their own adjudication process. You would have to start over and write entirely new rules based on federal law.

But I’m all for it.

Instead, I was forced into an agreement by the French to delay the hearing in return for my agreement to not race in France until a decision was rendered. It was damaging enough that I spent 200 thousand dollars flying lawyers to meet with the French agency to arrange this. But to have Mr. Brunet use my agreement with the French, in January 2007, as the starting date for my suspension while citing a rule about an accepted voluntary suspension, is nothing less than the abuse of the position he was given, all the while refusing to use that same power to balance things for my (the athletes’) side. Mr. Brunet knew, full well, that the agreement with the French was something about which I had no choice. After asking Mr. Brunet and WADA to ask the French for a stay, and being told in no uncertain terms that, not only would they not help, it was the position of Dick Pound that I deserved it. Mr. Brunet proceeded to use that agreement and obscure rules to begin my suspension on that date, six full months from when it would otherwise have begun were it not for the French Federal law.

However, all of those basic rights aside, the most egregious abuse of power (which would have been prevented were it a federal case) was the appointment of a fourth arbitrator into the process. Mr. Brunet and the other Canadian took it upon themselves to introduce a "panels expert" upon whom they would rely to explain the science when it became technical. Nowhere in the rules is this appointment ever contemplated, nevertheless, as this is not a federal proceeding, the panel is welcome to change and create rules along the way. This is how we came to have Dr. Botré, another WADA employee and colleague of the two Canadians, to serve as a witness to the panel after the hearing and with no opportunity for cross examination by my counsel. It is easy to decipher what transpired behind closed doors, among the panel. Dr Botré and the two Canadians wrote an incomprehensible decision, which, over and above being factually wrong, cannot even stand alone with all of its contradictions.

Were it a federal case, the jury would have been expected to disregard all testimony by the lineup of WADA lab directors USASA put forth. First Dr. Brenna, the WADA puppet who changed his testimony in the second half of the trial after learning that his testimony, the truth, would mean an exoneration because the math didn't work and so he made up a new technique called eyeballing. Dr. Catlin of UCLA then proudly took credit for having written the WADA “code of ethics” that clearly states that anyone who works for WADA in any capacity must take an oath to never testify against a WADA-accredited lab, in favor of an athlete. Why, having been so sure of their sound science, did USADA not bring one single scientist, out of the millions on earth, who was not on their payroll?

Most damning of all, Mr. Brunet is not expected to apply the same level of law-abiding perfection (“strict liability” to use the words of Dick Pound) to his own agency, the IOC, as they expect of each and every athlete — a standard which no government on earth would ever attempt to enforce on any citizen without expecting the same from the judges and police who accuse them.

In Mr. Brunet’s words, “Doping must be punished with the full force of our collective disapproval.” We can stone the dopers. We can stone everyone in sports. But until WADA holds up to the same standard expected of athletes, stone-throwing will solve nothing.

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Some legal questions from a reader

Maybe folks can answer these in comments:

What legal code will CAS be operating under? WADA "law" or Swiss law? Which one has precedence? If a question is not addressed by WADA law does Swiss law take over? Can this be exploited to allow discovery by the Landis team? Is Procedural Order 2 over, thereby allowing more discovery by the Landis team?

Can CAS set precedent? From a science perspective, there are significant and unresolvable problems with doing reliable data analysis on the LNDD chromatographs. TBV and Ali's extensive (impressive and very enjoyable) Idiot series takes one step by step through what a scientist should realize intuitively. Whether those problems are due to bad chemistry, system noise, obsolete/misused hardware or software, technician incompetence, or other factors would be interesting to know if one were a lab director looking to improve results and performance.

But from the appeal point of view, (it seems to me at least) it appears that USADA may be able to squirm out through the ambiguities of the WADA law. Larry and M's discussion on TD2003IDCR has laid bare the difficulty of nailing down WADA law. One thoughtful and unbiased (I'm assuming M is unbiased since most participants on this site obviously are;-) lawyer has confounded everyone's best efforts at finding the Holy Grail of ISL violations.

There is no technical requirement that data analysis can only be done on reliable data. There is no requirement that results must conform to scientific principles established through the peer-reviewed system.

Can CAS look at the perponderance of evidence and set precedence by saying that LNDD's results do not meet some minimum scientific requirement "inherent" in WADA law even if not explicitly stated by a WADA TD or ISL?

If not, then I'm afraid Landis' best hope is to get off on what the media would view as a "technicality" like COC issues.

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Monday Roundup

News
Reuters posts a piece about outgoing WADA president Dick Pound noting that few will shed tears at his exit, including Floyd Landis.

The CyclingNews covers Rabobank's independent investigation of Michael Rasmussen's dismissal from the team and the Tour de France last summer. The report notes that Rasmussen did not have personal reasons for the lie about his whereabouts and that he was ostensibly avoiding doping controls by doing so. It also said that he should never have started the Tour de France in the first place which implies some responsibility for the situation by the team itself, and the UCI does not escape the criticism of this committee either:

The International Cycling Union (UCI) also came in for a share of criticism in the report, which said that "The UCI must attain a higher level of professionalism with regard to the formulation, enforcement and monitoring of its own doping regulations."

In other news, the Jef D'Hont Jan ULlrich mess continues with former Ullrich mentor Rudy Pevenage getting into the fray. And Spain's Superior Council of Sports (CSD) president Jaime Lissavetzky comments on the upcoming anti-doping summit to be held in Madrid this week by making a strong statement that WADA needs to not only fight and eradicate doping, but it needs to do so fairly:

"There has been built a very useful model, but sometimes inflexible," he continued on how anti-doping laws have changed in the Iberian Peninsula. "We must find the balance between flexibility and efficiency. It is a relevant discussion beyond the case [Andrey] Kashechkin. We want to be against doping in sport and protect the health of the athlete, but also respect their fundamental rights, as contained in the anti-doping law in Spain."

The VeloNews also notes the independent report on the Rasmussen situation. And in the Monday Mailbag one note reveals biases for and against certain cyclists.


Blogs
Rant has found that the blood values Michael Rasmussen published last week tell a different story than might first be concluded.

JoeSchmo notes the exodus of sponsors from cycling because of doping scandals.

Racejunkie writes eloquently of "inconvenient truths" in the pro peloton, though after reading "Dopers Must Be Stoned" he may want to rethink referring to Floyd Landis as "goofily inarticulate".

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What Shackleton Did

In "Idiots look at Data", we wondered what Shackleton did to be sure he was looking at the right thing. The answer seems to be on GDC 1100. We learn that he did the GCMS at one site, then shipped the samples to another site, not unlike the two machine setup at LNDD over a longer distance.

Confirmation of identity of steroids in extracts.

Prior to sending the first samples for GC/C/IRMS analyses in England, the identities of the principal components of the chromatogram were confirmed by GC/MS. This was carries out on a Hewlett-Packard 5970 instrument housing a 15 meter DB1 capillary column. The peaks chosen for GC/C/IRMS analyses had retention times and electrion impact mass spectra identical to those of 5a- and 5b-androstanediol diacetate and pregnanediol diacetate. Reference steroid for these compounds were also analyszed on the GC/C/IRMS instrument using both DB1 and DB17 columns, and these gave identical retention times to the urinary steroids. Pregnanetriol could also be analyzed by GC/C/IRMS.

It is not clear to us from reading this if impact MS data were acquired and analyzed at the GC/C/IRMS site, or only from the GC/MS site.

I'm not smart enough to tell if Shackleton's chemistry is the same as what we know of LNDD's.

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Idiots look at Data, Part VIII: The Insecurity Index

Throughout our look at chromatograms and parts of chromatograms, we've been counting things that look like they might be problems in the data set. We are not saying they are problems, we're saying they are things that may cause concern. The higher the number, the more careful we want to be about interpreting the data.

Adding up all the numbers we get an aggregate we'll call the Idiot's Insecurity Index (I3), pronounced, "aye-yi-yi". It consists of:

• The Number of peaks
• Rating of the baseline slope on a 1 to 5 scale.
• Rating of bumpiness of the background on a 1 to 5 scale.
• On the peaks of interest, the total count of shoulders, leading or trailing edges, connections to neighbors above the baseline, and the number of neighbors within one peak-width at the baseline.
  

It is not a threshold; there aren't limits. It applies to all chromatograms. Higher values are cause for notice, and evaluation, and confirmation.

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Let's look at two trivial examples, one from UCLA, and one from the LNDD and score them.

Figure 1: UCLA reference pulses.

UCLA: 3 peaks, flat slope = 1, no bumps = 1, total shoulders = 0, total edges = 0, total connections = 0, neighbors in one peak = 0, total = 5.

Figure 2: LNDD reference pulses

LNDD: 3 peaks, flat = 1, no bumps = 1, shoulders 0, edges = 3, connections = 0, neighbors, charitably = 0, total = 8. Given a choice, it might be better for them to be spaced a little further apart, and the trails on the pulses might indicate a problem somewhere in the system, we think.

So given the I3 and the scores we made all along, where are we with our look at the data in previous parts? We could make you go to another post or page, like a computer hardware review sites, but we'll be nice:

Test	Pks	Slp	Bmp	Shldr	Edg	Conn	Nbrs	I3
UCLA	12	1	1	2 2 0	0 1 0	0 0 0	0 0 0	19
Ex 92 3-Jul	36	3	2	2 1 2	0 1 0	2 2 0	3 1 1	56
Ex 88 13-Jul	33	5	2	2 2 1	0 0 0	2 2 0	3 3 1	56
Ex 90 14-Jul	36	5	1	2 1 1	0 0 0	2 2 0	2 2 1	55
Ex 86	47	5	3	2 2 1	0 0 0	2 2 0	2 2 1	69
USADA 173	29	3	1	2 2 2	0 1 0	0 2 0	2 2 1	47
USADA 349	27	3	1	1 2 1	0 1 0	2 2 0	2 2 1	44
Ex 87 22-Jul	39	2	2	1 1 0	0 1 0	1 2 1	1 2 3	56
Ex 84 23-Jul	32	1	3	1 1 0	0 1 0	2 2 1	2 2 3	51
Ex 93 control	22	1	2	1 1 1	1 1 0	0 2 1	0 2 3	38
Ex 85 control	35	2	3	1 1 1	1 2 0	0 2 1	1 2 2	54
Ex 89 control	36	2	2	1 1 1	1 1 0	1 2 1	1 4 3	57
Shack fig3a	17	1	1	0 1 1	0 1 1	0 2 0	0 4 0	29
Shack fig3b	19	2	1	0 0 2	0 1 0	0 2 0	0 1 0	27

This is bogus, you say. However, it follows thinking used in Software Engineering in measures such as the McCabe complexity, or the Halstead volume, or arguably function points. A chromatogram with an I3 of two is like a software subroutine that does nothing: Useless, but absolutely correct. On the other hand, one with an I3 of 200 is like a 10 page software function with a McCabe of 2000 -- it might appear to be correct, but how do you really know without looking very closely indeed?

Bigger numbers mean more stuff.

More stuff means more opportunity for error. The more stuff you have, the more careful you need to be about checking assumptions and pre-conditions.

In an earlier post, M has made comments suggesting it is unfair or improper to make some of the comparisons made here. We disagree; as shown above, the methodology is perfectly applicable to a straight line background or a series of reference pulses. It is a measure of the potential for problems, not an assertion there are problems.

M also suggested one reason it was unfair was that chemistry in the F3 fraction was more difficult than that of the F2 fraction. It is true the F3 chemistry is more difficult, and appreciate that admission from M. It raises the very question we'd like to ask.

How do you tell if the chemistry does the job properly?

One indicator is to look at the I3 of the resulting chromatograms.

Thanks to M's diligence, we found the Shackleton chromatograms that also reveal the 5bA and 5aA, so we do have fair, like-to-like comparisons. They appear to be much cleaner by I3 score than those produced by LNDD.

What did Shackleton do that LNDD didn't? This bears investigation.

When we started this series, we said that the preconditions for correctness in the integration that computes the numbers in a CIR result are:

• Clean, unambiguous baselines suggesting good chemical separation of the prepared samples. This is reflected in the count of the peaks in the chromatogram. Good chemistry give fewer peaks to be concerned about, and fewer unknowns floating about.
  
• Significant (a debatable term) baseline (chromatographic) separation of peaks. We've demonstrated that co-elutes can cause unexpected skews of significant magnitude.
  
• Absence of shoulders suggesting unidentified peaks. Where there are shoulders or tails, there may be unidentified co-elutes.
  
• Measurement of nearby peaks to consider their potential for influence. We may back away from this thought, but it seem like you ought to know the CIR of every adjacent peak in case it is co-eluting in some way.

Idiots such as ourselves looking at all the LNDD chromatograms can see all stuff we don't see in the UCLA and Shackleton chromatograms, and some cases of very odd baselines in some cases.

Maybe LNDD's chemistry isn't separating as well as it ought to, and needs to.

If there is lots of stuff around, it is going to go somewhere. A high I3 score makes it prudent to be sure the peaks being measured contain only what they are purported to contain.

As we demonstrated in "Integration for Idiots", presence of unexpected material can invalidate any reported numeric results.

We are thus left with some questions to seed further discussion.

• What does UCLA do to ensure purity of peaks?
• What did Shackleton do to ensure purity of peaks?
• What did LNDD do to ensure purity of peaks?
• 
  

That is the end of "Idiots look at Data" for us.

Feel free to chop apart individual assessments and argue whether certain pixels represent particular flaws, and whether they have particular numeric significance in a particular test. This doesn't much interest us. At a scientific level, either the protocol is flawed and there is flawed data being processed and reported, or it is good data and good results. At the moment, indications such as the I3 suggest the data may not be good. A good process will be able to demonstrate the data is good.

We have said for a long time, if we can get confirmation the data is clean and pure, we're prepared to accept the numeric conclusions at a scientific level.

If there is no validation the data is clean and pure enough to trust, there is a different, legal question whether the reported results are correct.

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