Every letter we have printed
Page 65 of 77 of this archive, newest first.
On “The anatomy of the most reproduced page in this trade” — Explainers, 1 Jun 2024
A technical query on your identity row: you specify 4111.1 Da monoisotopic with a tolerance of ±10 ppm, which is 0.04 daltons. Is that not tighter than most contract laboratories will commit to on a peptide of that size?
— F. Duquesne, Lyon
It is achievable on an orbital trap with internal calibration and is tight for a quadrupole time-of-flight on external calibration. The row is drawn from a real certificate issued by a laboratory running the former. We should have said so, and the note now does.
On “The anatomy of the most reproduced page in this trade” — Explainers, 1 Jun 2024
The most useful sentence in the piece is the one saying a bad document is not a bad product. I have spent two years on forums watching people conclude the opposite from a missing signature block, and it has made the whole conversation about honesty rather than about paperwork.
— S. Nortje, Stellenbosch
That inversion is the reason we wrote the final section, and we would rather be accused of excessive caution than contribute to it.
On “The anatomy of the most reproduced page in this trade” — Explainers, 1 Jun 2024
I supply research peptides and I want to push back on the specification column point. We sell from a catalogue of six hundred products. Writing a meaningful individual specification for each would take a year of somebody’s time, and a generic one would be exactly the decorative limit your article criticises. What would you actually have us do?
— T. Kirchner, Hamburg
A fair challenge. Our answer is that a generic limit stated honestly is better than no limit at all, provided the typical result is also published so a reader can see the margin. What we object to is a decorative limit presented as a control. Publishing your process capability alongside it removes the objection entirely, and costs you a spreadsheet.
On “The anatomy of the most reproduced page in this trade” — Explainers, 1 Jun 2024
On the accreditation-scope point: most private buyers will not know which accreditation body to search. It would be more useful to publish the four or five registers that cover the laboratories this market actually uses than to tell readers the registers exist.
— J. Wenninger, Graz
Agreed, and the standards desk is compiling exactly that. It will appear as a standing reference page rather than inside an article, so that it can be kept current.
On “Pancreatitis, obstruction, gallbladder: three things nausea can be” — Explainers, 1 Jun 2024
As an anaesthetist I read the perioperative section with interest and one objection. You frame disclosure as the patient obligation. In my experience the failure is more often ours: the pre-assessment questionnaire in my own institution did not include these drugs until eighteen months after the first guidance appeared.
— A. Chowdhury, Dhaka
A fair correction and we have amended the text. If the question is not on the form, the absence of an answer is not a patient failure. We would be interested to hear from readers in other institutions about whether their pre-assessment documentation has caught up.
On “Pancreatitis, obstruction, gallbladder: three things nausea can be” — Explainers, 1 Jun 2024
The gallbladder section says some of the excess is attributable to weight loss rather than the drug. If the drug causes the weight loss, is that not a distinction without a difference for the person who ends up in theatre?
— M. Bogdanović, Podgorica
For the individual, largely yes. For the question of whether one molecule is safer than another, or whether the risk would fall on slower loss, the distinction is the whole question. We should have made clear that it is a mechanistic distinction rather than a consoling one.
On “Pancreatitis, obstruction, gallbladder: three things nausea can be” — Explainers, 1 Jun 2024
You note that symptom burden does not predict weight outcome. This is the single most useful sentence I have read about this treatment. I spent four months believing that feeling well meant it was not working and considered increasing my dose on that basis alone.
— F. Okonjo, Asaba
The folk model that suffering indexes efficacy is widespread and the published analyses do not support it. It is also actively harmful when it drives escalation, which is why we gave it a line in the closing section rather than burying it in the tables.
On “A schedule that bends does not break” — Pharmacology, 1 Jun 2024
The claim that nobody has randomised escalation intervals is too strong. There are protocol amendments in several programmes that effectively created slower-titration cohorts, and some of those have been analysed post hoc.
— D. Ferreira-Lopes, Porto
Post-hoc comparison of cohorts created by amendment is not randomisation, and treating it as such is exactly the elision we were objecting to. We accept that such analyses exist and are informative; we maintain that they cannot settle the question, and the file now says so in those terms.
On “A schedule that bends does not break” — Pharmacology, 1 Jun 2024
You describe the plateau as an energy-balance event and dismiss receptor desensitisation. Is there not a third possibility — that adherence quietly falls off at around a year and the plateau is partly a behavioural artefact of the trial rather than a physiological one?
— A. Petrucci, Bari
There is, and it is a better objection than the desensitisation argument. Adherence does decline over the second year of the long programmes, and the treatment-policy analyses absorb that decline into the mean. We should have said that the plateau is very likely a composite of energy balance and falling adherence, in proportions the published analyses do not separate cleanly.
On “A schedule that bends does not break” — Pharmacology, 1 Jun 2024
I had a nine-week gap last year because my supplier stopped answering messages. Nobody in any clinical setting I dealt with treated that as a pharmacological event. Your framing of supply interruption as a dosing decision is the first time I have seen it written down.
— B. Ademola, Ilorin
On “What the protein literature actually shows, and in whom it was shown” — Clinical Trials, 29 May 2024
You write that no trial has measured strength. There are observational cohorts with grip strength data. Why do you insist on randomised measurement?
— M. Sandhu, Amritsar
Because grip strength in an observational cohort of people who chose to take a drug, and who differ from those who did not in age, motivation and comorbidity, cannot separate the drug effect from the selection. We report those cohorts and we do not treat them as answering the question.
On “The figure of merit this trade chose, and the four it did not” — Laboratory Notebook, 27 May 2024
On the section about diode-array detection and peak purity, I would add that true peak purity assessment requires library matching or at least spectral comparison across the peak width. A homogeneous spectrum tells you the peak is probably pure. A spectrum that shifts across the peak tells you it is not, and that information closes a gap the article identifies correctly.
— N. Villaseñor, Guadalajara
On “The figure of merit this trade chose, and the four it did not” — Laboratory Notebook, 27 May 2024
You write that only one laboratory attached its chromatogram to the private buyer report. That was probably us. We started doing it five years ago because the PDF seemed incomplete without it. It costs us nothing to add — the instrument generates it automatically — and it solves exactly the dispute-resolution problem you describe. More laboratories should do it, and the reason they do not is not technical.
— N. Zangwill, Manchester
That is generous of you to say. The technical barrier is near zero, and if enough laboratories began printing them, it would force the convention to change across the market. It is an example of something that costs one actor almost nothing but creates value for everyone, and it is precisely the kind of thing that can shift a trade practice when a few leaders move first.
On “The figure of merit this trade chose, and the four it did not” — Laboratory Notebook, 27 May 2024
Something your article omits, and it changes where the responsibility sits. Method selection is frequently specified by the customer, not by us. A purchase order arrives asking for a peptide purity run at a stated price and turnaround, and the method that fits those two constraints is the method that runs. We are perfectly willing to develop a longer separation for anybody who wants one, and in eleven years almost nobody has asked.
— P. Havlíček, Brno
That is a genuinely different account of the causation from the one we gave, and if it generalises it matters. Our piece treats method choice as a laboratory decision and yours treats it as a procurement decision. We would like to test which it is, and we are writing to the four independent services to ask what proportion of incoming work specifies a method at all.
On “The figure of merit this trade chose, and the four it did not” — Laboratory Notebook, 27 May 2024
Your worked example varies gradient and threshold together and reports a 1.8-point spread. Which of the two contributed more? The article does not say, and the answer matters for what you are asking suppliers to disclose first.
— B. Achterberg, Utrecht
Gradient, by roughly two to one in our four conditions: holding the threshold at 0.10 per cent, lengthening the gradient cost 0.9 points, while holding the gradient and tightening the threshold cost 0.4 to 0.9 depending on which gradient. We should have printed that decomposition in the table and it now appears in the note. If a supplier will disclose only one value, it should be the gradient.
On “The figure of merit this trade chose, and the four it did not” — Laboratory Notebook, 27 May 2024
On response factors: you say correction requires isolated impurity standards, which is true, but you might mention that charged aerosol and mass-based detection sidestep the problem by responding more uniformly. Neither is exotic any more.
— C. Tremonti, Palermo
On “Endotoxin is not a microorganism, and killing the bacteria does not remove it” — Analytics, 25 May 2024
You write that recombinant factor C is insensitive to the glucan branch of the cascade. It would be worth adding why anybody cares: cellulose filter media and certain paper wrappings shed glucans, and a laboratory that has chased a false positive through three repeat assays will never willingly go back to a reagent that responds to them.
— D. Ó Súilleabháin, Killarney
On “The anatomy of the most reproduced page in this trade” — The Supply Chain, 24 May 2024
I supply research peptides and I want to push back on the specification column point. We sell from a catalogue of six hundred products. Writing a meaningful individual specification for each would take a year of somebody’s time, and a generic one would be exactly the decorative limit your article criticises. What would you actually have us do?
— T. Oyelowo, Abeokuta
A fair challenge. Our answer is that a generic limit stated honestly is better than no limit at all, provided the typical result is also published so a reader can see the margin. What we object to is a decorative limit presented as a control. Publishing your process capability alongside it removes the objection entirely, and costs you a spreadsheet.
On “The anatomy of the most reproduced page in this trade” — The Supply Chain, 24 May 2024
The most useful sentence in the piece is the one saying a bad document is not a bad product. I have spent two years on forums watching people conclude the opposite from a missing signature block, and it has made the whole conversation about honesty rather than about paperwork.
— S. Bergqvist, Malmö
That inversion is the reason we wrote the final section, and we would rather be accused of excessive caution than contribute to it.
On “The anatomy of the most reproduced page in this trade” — The Supply Chain, 24 May 2024
A technical query on your identity row: you specify 4111.1 Da monoisotopic with a tolerance of ±10 ppm, which is 0.04 daltons. Is that not tighter than most contract laboratories will commit to on a peptide of that size?
— K. Sivertsen, Bergen
It is achievable on an orbital trap with internal calibration and is tight for a quadrupole time-of-flight on external calibration. The row is drawn from a real certificate issued by a laboratory running the former. We should have said so, and the note now does.
On “The anatomy of the most reproduced page in this trade” — The Supply Chain, 24 May 2024
You put every documentary finding to the company before publication, which is admirable and also means you are letting companies that do not reply escape coverage entirely. Silence should have a cost.
— J. Vasilenko, Chisinau
It does, and we should make it more visible. Non-response is recorded in the dossier register and published there. What we will not do is publish an inference we cannot support merely because nobody objected to it, and that constraint does protect the unresponsive. We accept the trade knowingly.
On “Why "muscle-sparing" is a marketing term and not a measurement” — Clinical Trials, 24 May 2024
As a DXA technologist of twenty-two years I would add one thing to your precision section: the largest source of error in practice is not the machine, it is positioning. A patient scanned with their arms two centimetres further from their trunk will report different regional values. We are trained to a protocol and the protocol is not always followed.
— S. Ó Ceallaigh, Limerick
We should have said this and did not. It also argues for what you presumably practise: same device, same technologist, same protocol, and a note in the record when any of those changes.
On “Why "muscle-sparing" is a marketing term and not a measurement” — Clinical Trials, 24 May 2024
You write that no trial has measured strength. There are observational cohorts with grip strength data. Why do you insist on randomised measurement?
— R. Cadogan, Bridgetown
Because grip strength in an observational cohort of people who chose to take a drug, and who differ from those who did not in age, motivation and comorbidity, cannot separate the drug effect from the selection. We report those cohorts and we do not treat them as answering the question.
On “Why "muscle-sparing" is a marketing term and not a measurement” — Clinical Trials, 24 May 2024
My mother is eighty-one and on a low dose for her diabetes. Her weight is down nine kilograms and she now struggles to get out of a low chair, which she did not eighteen months ago. Nobody has measured anything. I do not know whether this is the drug, the weight loss, or being eighty-one, and neither does anybody I have asked.
— K. Mwangi, Nakuru
That is the situation the missing endpoint produces, and we are sorry to have no better answer. A chair-stand time takes thirty seconds to measure and would at least establish a baseline against which the next six months could be judged. It is worth asking for by name.
On “Why "muscle-sparing" is a marketing term and not a measurement” — Clinical Trials, 24 May 2024
The soft-tissue artefact point in your bone section is underplayed. In a patient losing twenty per cent of body mass the change in overlying tissue is well outside the range the calibration was validated over, and the published analyses do not report a sensitivity analysis for it. That is not a caveat, it is a gap.
— D. Ó Súilleabháin, Killarney
We accept the escalation and have strengthened the wording. The absence of any published sensitivity analysis is, as you say, the more damaging observation.
On “Why "muscle-sparing" is a marketing term and not a measurement” — Clinical Trials, 24 May 2024
Small correction to your table: the S-LiTE exercise prescription was two supervised group sessions and two individual sessions weekly, not two sessions in total. The distinction matters because "add some exercise" is not what was tested.
— M. Tsvangirai, Bulawayo
Correct, and that is precisely the point we were trying to make and then undermined in our own table. Amended.
On “The lead-in, the randomisation, and the year that followed” — The Ledger, 23 May 2024
Your piece describes tapering as pharmacologically pointless and then spends three paragraphs making a case for it. Pick one.
— O. Brannigan, Galway
Both, we think, and deliberately. There is no pharmacological rationale, because there is no withdrawal syndrome and a week-long half-life produces its own decline. There is a behavioural rationale, which is different in kind and untested. Our objection is to tapers advocated in pharmacological language, not to the practice.
On “Escalating past the approved maximum, examined honestly” — Pharmacology, 23 May 2024
You describe the plateau as an energy-balance event and dismiss receptor desensitisation. Is there not a third possibility — that adherence quietly falls off at around a year and the plateau is partly a behavioural artefact of the trial rather than a physiological one?
— T. Wexford, Louisville, KY
There is, and it is a better objection than the desensitisation argument. Adherence does decline over the second year of the long programmes, and the treatment-policy analyses absorb that decline into the mean. We should have said that the plateau is very likely a composite of energy balance and falling adherence, in proportions the published analyses do not separate cleanly.
On “Escalating past the approved maximum, examined honestly” — Pharmacology, 23 May 2024
The claim that nobody has randomised escalation intervals is too strong. There are protocol amendments in several programmes that effectively created slower-titration cohorts, and some of those have been analysed post hoc.
— D. Lockridge, Tulsa, OK
Post-hoc comparison of cohorts created by amendment is not randomisation, and treating it as such is exactly the elision we were objecting to. We accept that such analyses exist and are informative; we maintain that they cannot settle the question, and the file now says so in those terms.
On “What we are not saying about anybody in this trade” — Laboratory Notebook, 22 May 2024
Why did you submit only two vials for sterility testing when the whole article argues that the sample size is the problem? Two is worse than twenty by exactly the argument you make.
— R. Hollenbeck, Spokane, WA
Because we could not afford twenty, and because the two results are reported as what they are: two vials, each destroyed, telling us nothing about their batches. The purpose was to establish that the test is commercially available to a private purchaser and what it costs, not to characterise anything. We should have said that in the article rather than in this reply.
On “What we are not saying about anybody in this trade” — Laboratory Notebook, 22 May 2024
On multiple-dose closures: the puncture budget you refer to is generally in single figures for a standard lyophilisation stopper, and the qualification uses a new needle each time. Anybody reusing a needle through the same entry point is outside the data entirely.
— H. Baptiste, Fort-de-France
On “What we are not saying about anybody in this trade” — Laboratory Notebook, 22 May 2024
You keep saying you are criticising documentation and not honesty. I think that distinction is doing more work than it can bear. If a company knows buyers read a purity certificate as a safety document and issues one anyway, the omission is doing something.
— N. Halvorsen, Trondheim
It is a fair challenge and we have thought about it. Our answer is that the convention long predates any individual company’s decision to follow it, that four of our correspondents told us plainly the products are not represented as sterile injectables, and that we have no evidence of anybody intending the inference readers draw. We will report intent when we can demonstrate it and not before.
On “What we are not saying about anybody in this trade” — Laboratory Notebook, 22 May 2024
I photograph every cake now because of an earlier piece of yours, and last month it paid for itself. Two vials from the same box, one a proper matte plug and one a collapsed glassy disc. The supplier replaced both without argument when I sent the photographs.
— T. Elorriaga, San Sebastián
On “Maximum tolerated is not maximum approved” — Patient Notes, 21 May 2024
I had a nine-week gap last year because my supplier stopped answering messages. Nobody in any clinical setting I dealt with treated that as a pharmacological event. Your framing of supply interruption as a dosing decision is the first time I have seen it written down.
— R. Ekwueme, Awka
On “Why "muscle-sparing" is a marketing term and not a measurement” — Clinical Trials, 19 May 2024
I train four times a week, eat a hundred and sixty grams of protein and my appendicular lean mass has fallen by 1.8 kg over ten months while every lift has gone up. Your section on mass against function was the first thing I have read that made that seem normal rather than a failure.
— T. Brannon, Boise, ID
On “Why "muscle-sparing" is a marketing term and not a measurement” — Clinical Trials, 19 May 2024
Your piece treats the one-quarter rule as discredited and then quotes fractions of one third and two fifths from the substudies as though those were more solid. They are group means from a hundred and forty people. Physician, heal thyself.
— S. Lindgren, Uppsala
A fair hit, and we have amended the paragraph to carry the same caveat in both places. The distinction we should have drawn is that the substudy figures are at least attached to a stated population and a stated instrument, which the textbook rule is not. Neither is a constant.
On “What the paperwork is for, and who it was designed to protect” — Analytics, 18 May 2024
Nine years buying research chemicals and I had never once looked at the date of manufacture. I checked eleven certificates in my drawer this evening. Four do not carry one.
— M. Ferrari, Trieste
On “What the paperwork is for, and who it was designed to protect” — Analytics, 18 May 2024
The composite test table you print as a model is unrealistic. No research supplier is going to run headspace GC and ion chromatography on every lot at these price points, and publishing an aspirational document as a benchmark just makes real certificates look worse than they are.
— K. Rautio, Tampere
The table note says explicitly that no supplier in our programme issues a document containing every row, and it is offered as a reference rather than as a demand. But you have a point about framing, and we have moved the caveat from the note into the caption.
On “What the paperwork is for, and who it was designed to protect” — Analytics, 18 May 2024
You put every documentary finding to the company before publication, which is admirable and also means you are letting companies that do not reply escape coverage entirely. Silence should have a cost.
— H. Barreto, Recife
It does, and we should make it more visible. Non-response is recorded in the dossier register and published there. What we will not do is publish an inference we cannot support merely because nobody objected to it, and that constraint does protect the unresponsive. We accept the trade knowingly.
On “What the paperwork is for, and who it was designed to protect” — Analytics, 18 May 2024
A technical query on your identity row: you specify 4111.1 Da monoisotopic with a tolerance of ±10 ppm, which is 0.04 daltons. Is that not tighter than most contract laboratories will commit to on a peptide of that size?
— C. Wilcoxson, Des Moines, IA
It is achievable on an orbital trap with internal calibration and is tight for a quadrupole time-of-flight on external calibration. The row is drawn from a real certificate issued by a laboratory running the former. We should have said so, and the note now does.