Every letter we have printed
Page 75 of 77 of this archive, newest first.
On “Why receptor selectivity is the least discussed number in incretin…” — Pharmacology, 26 Jan 2024
I found the section on the area postrema genuinely clarifying. I had assumed nausea was a stomach problem and had been treating it as one, unsuccessfully, for four months.
— Z. Karadzic, Novi Sad
On “How a claim degrades between the bench and the listing” — The Supply Chain, 26 Jan 2024
As a buyer I found the section on who chose the vial genuinely clarifying and slightly deflating. I have been treating vendor-published reports as equivalent to my own submissions for two years, and on your account they are not equivalent by an amount that cannot be measured.
— H. Nakagawa, Fukuoka
That is the correct reading, and the unmeasurable part is the honest part. We would add only that vendor-published reports are not worthless — a vendor willing to commission testing at all is behaving better than one that will not — they are simply weaker in a specific way.
On “How a claim degrades between the bench and the listing” — The Supply Chain, 26 Jan 2024
Your selection-effect model assumes a supplier publishes results above a fixed threshold. Real behaviour is surely more complicated: a supplier might publish a poor result on a batch it has withdrawn, or publish everything for a period to establish credibility and then stop. The arithmetic is fine and the behavioural assumption is a cartoon.
— A. Salcedo, Bilbao
Agreed, and the figure caption now says illustrative arithmetic rather than model. The point survives the simplification, which is that a small amount of selection produces a large apparent effect, but we should not have dressed a demonstration as an estimate.
On “Resolving power and mass accuracy are two different specifications” — Explainers, 25 Jan 2024
The claim that a reproduced spectrum is worth more than any number in the document seems overstated. Most buyers cannot read a spectrum, and a printed image invites false confidence rather than scrutiny.
— K. Rautio, Tampere
Partly conceded. A spectrum is worth more to a reader who can read one, and this department exists partly to increase that number. But it is also an artefact that can be checked by a third party later, which a bare verdict is not, and that alone justifies printing it.
On “Resolving power and mass accuracy are two different specifications” — Explainers, 25 Jan 2024
Sixteen years in a peptide plant and I have never once been asked by a customer which ionisation source we used. I have been asked hundreds of times for a purity figure to one more decimal place.
— M. Ferrari, Trieste
On “Resolving power and mass accuracy are two different specifications” — Explainers, 25 Jan 2024
You state that fourteen of twenty suppliers report an MS identity test. Does that count reports supplied to you on request, or only what appears on the certificate a customer receives?
— C. Wilcoxson, Des Moines, IA
The former, which the table note now says explicitly. The count for what appears on a customer-facing certificate is lower in at least four cases, and we should have separated the two columns rather than merging them.
On “Resolving power and mass accuracy are two different specifications” — Explainers, 25 Jan 2024
On your point about D-amino acids: chiral amino-acid analysis after hydrolysis is not exotic and several contract laboratories offer it. The obstacle is that hydrolysis itself racemises a few per cent of most residues, so the method has a blank problem, and interpreting a low-level D content is genuinely difficult rather than merely expensive.
— H. Barreto, Recife
An important qualification and we are glad to have it. The article implied the barrier was commercial when a substantial part of it is methodological. Recorded, and the section has been rewritten accordingly.
On “Why people actually stop, in the order they actually stop” — The Ledger, 24 Jan 2024
You describe the maintenance strategy of stepping down one dose and holding for eight to twelve weeks as something clinicians report doing, and then say it is not a recommendation. That distinction will be lost on most readers, and printing the protocol makes you a source for it whether you intend to be or not.
— J. Costanzo, Naples
This is the hardest editorial question this department faces and we do not think you are wrong. Our position is that a practice this widespread is better described accurately, with its evidentiary status stated, than left to circulate in fragments. We accept that the distinction does work that a reader may not do.
On “Why people actually stop, in the order they actually stop” — The Ledger, 24 Jan 2024
I stopped eight months ago after reaching a weight I was happy with, and I have regained four of the twenty-two kilograms I lost. Every article I read told me to expect two-thirds back. I am not complaining, but I would like to know whether I am unusual or whether the two-thirds figure was always a mean concealing an enormous range.
— E. Nkomo, Polokwane
The second. The published interquartile ranges around those means are wide, and outcomes like yours are well within them. The trials were not designed to explain why some people hold weight after cessation and others do not, and nothing measured at randomisation predicts it usefully. You are not an anomaly; you are part of a distribution nobody quotes.
On “Why people actually stop, in the order they actually stop” — The Ledger, 24 Jan 2024
Your fortnightly arithmetic table is correct but I think it understates the practical point. A fourfold peak-to-trough swing is not merely lower average exposure; it is a different drug experience, with the last few days of each cycle spent at a concentration the person has effectively titrated off.
— G. Rasmussen, Odense
Well put, and better than our own phrasing. We have adopted the point in the text with attribution to a reader.
On “Site selection when the tissue has already changed” — Laboratory Notebook, 24 Jan 2024
Your rotation advice says site does not affect absorption in this class, and then says to rotate anyway. If absorption is unaffected, why bother?
— E. Sørheim, Stavanger
Because rotation protects tissue rather than controlling absorption. Repeated injection into one small area produces lipohypertrophy, and absorption from lipohypertrophic tissue is blunted and erratic for any injected depot. Rotation prevents the condition that would make site matter. The advice is consistent; we should have made the causal order clearer.
On “The certificate says 2024. The vial in your hand does not say anything.” — The Supply Chain, 23 Jan 2024
You describe reused chromatogram images as a tell. I work in a contract laboratory and I would note that some data systems export a representative overlay rather than the individual injection, so identical-looking traces can occur legitimately across a batch series. It is still worth asking about; it is not the smoking gun your article implies.
— D. Ramkissoon, Port of Spain
A useful qualification and the text has been softened. The observation remains worth making; the inference we drew from it was stronger than the practice supports.
On “The certificate says 2024. The vial in your hand does not say anything.” — The Supply Chain, 23 Jan 2024
Your ten-minute check told me in about ninety seconds that the batch number on my certificate appears nowhere on the vial. I wrote to the supplier and had a straightforward answer within a day: the certificate covers the bulk lot and the vial carries a fill code. I would never have known to ask.
— P. Kovalenko, Lviv
That is exactly the intended use, and the supplier’s answer is the correct one. The remaining question is why the relationship between the two codes is not printed on the document, since it takes a line.
On “The certificate says 2024. The vial in your hand does not say anything.” — The Supply Chain, 23 Jan 2024
I have a certificate with an expiry date twenty-four months from manufacture and no stability data behind it, which your article says is a claim the documentation cannot support. The supplier tells me it is industry standard. Is it?
— C. Adeoti, Ibadan
Twenty-four months is a common default and “industry standard” is an accurate description of the practice rather than a justification of the claim. The distinction we would press is between an expiry date, which asserts shelf life, and a retest date, which asserts only a review interval. The second is defensible without stability data. The first is not.
On “Dose-limiting: a definition worth being strict about” — Patient Notes, 23 Jan 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.
— J. Vasilenko, Chisinau
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 “Dose-limiting: a definition worth being strict about” — Patient Notes, 23 Jan 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?
— K. Sivertsen, Bergen
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 “Seasonal use, holiday use, and the honest state of the evidence” — Clinical Trials, 22 Jan 2024
Three months after stopping, my HbA1c had barely moved and I concluded I had got away with it. Six months after stopping, it was back where it started. Your point about the lag is the single most useful sentence I have read on this subject.
— N. Zangwill, Manchester
On “Seasonal use, holiday use, and the honest state of the evidence” — Clinical Trials, 22 Jan 2024
Your fortnightly arithmetic table is correct but I think it understates the practical point. A fourfold peak-to-trough swing is not merely lower average exposure; it is a different drug experience, with the last few days of each cycle spent at a concentration the person has effectively titrated off.
— N. Villaseñor, Guadalajara
Well put, and better than our own phrasing. We have adopted the point in the text with attribution to a reader.
On “Seasonal use, holiday use, and the honest state of the evidence” — Clinical Trials, 22 Jan 2024
I stopped eight months ago after reaching a weight I was happy with, and I have regained four of the twenty-two kilograms I lost. Every article I read told me to expect two-thirds back. I am not complaining, but I would like to know whether I am unusual or whether the two-thirds figure was always a mean concealing an enormous range.
— B. Achterberg, Utrecht
The second. The published interquartile ranges around those means are wide, and outcomes like yours are well within them. The trials were not designed to explain why some people hold weight after cessation and others do not, and nothing measured at randomisation predicts it usefully. You are not an anomaly; you are part of a distribution nobody quotes.
On “Seasonal use, holiday use, and the honest state of the evidence” — Clinical Trials, 22 Jan 2024
You describe the maintenance strategy of stepping down one dose and holding for eight to twelve weeks as something clinicians report doing, and then say it is not a recommendation. That distinction will be lost on most readers, and printing the protocol makes you a source for it whether you intend to be or not.
— P. Havlíček, Brno
This is the hardest editorial question this department faces and we do not think you are wrong. Our position is that a practice this widespread is better described accurately, with its evidentiary status stated, than left to circulate in fragments. We accept that the distinction does work that a reader may not do.
On “Seasonal use, holiday use, and the honest state of the evidence” — Clinical Trials, 22 Jan 2024
I lost access for eleven weeks during the shortage, restarted at the dose I had been on because nobody told me otherwise, and spent a fortnight unable to keep food down. I had been on that dose for seven months without difficulty. Reading your resumption section was the first time anybody explained it.
— G. Thorbjørnsen, Tromsø
It is entirely predictable from the label and the pharmacokinetics, and the failure to communicate it during the shortage period was systemic rather than individual. We are sorry it reached you this way and we are glad it reached you.
On “Target dose, effective dose, and the distance between them” — Pharmacology, 21 Jan 2024
Your piece treats the four-week step as arithmetic, and I accept the arithmetic, but my prescriber moved me up every two weeks and I reached the top dose without difficulty. I do not think the schedule is as constraining as you suggest.
— P. Sarkissian, Beirut
Nor do we, and the file should have been clearer. The four-week interval is a floor below which the previous rung is still accumulating, not a threshold below which escalation is unsafe. Plenty of people tolerate faster ascent. Our objection is to the inverse inference — that because you did, everybody should — and to the absence of a trial that would let anyone say which is which in advance.
On “Target dose, effective dose, and the distance between them” — Pharmacology, 21 Jan 2024
You keep insisting on peptide content rather than purity when discussing dose certainty. I have looked at a dozen certificates from four different testing services and content is reported on perhaps a third of them. What are readers supposed to do with an absence?
— J. Delahunty, Waterford
Treat the nominal figure as an upper bound and say so out loud when reasoning about a dose. It is an unsatisfying answer and it is the honest one. We have argued in Analytics that content should be a standard reported field, and we will keep naming the services that report it and those that do not.
On “Retest date, expiry date, and the two conventions being confused” — The Supply Chain, 21 Jan 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?
— N. Bujanović, Sarajevo
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 “Retest date, expiry date, and the two conventions being confused” — The Supply Chain, 21 Jan 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. Tovmasyan, Gyumri
That inversion is the reason we wrote the final section, and we would rather be accused of excessive caution than contribute to it.
On “Retest date, expiry date, and the two conventions being confused” — The Supply Chain, 21 Jan 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?
— H. Okwuosa, Enugu
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 “Deamidation, oxidation, and the two shifts worth memorising” — Explainers, 20 Jan 2024
On your point about D-amino acids: chiral amino-acid analysis after hydrolysis is not exotic and several contract laboratories offer it. The obstacle is that hydrolysis itself racemises a few per cent of most residues, so the method has a blank problem, and interpreting a low-level D content is genuinely difficult rather than merely expensive.
— T. Wexford, Louisville, KY
An important qualification and we are glad to have it. The article implied the barrier was commercial when a substantial part of it is methodological. Recorded, and the section has been rewritten accordingly.
On “Deamidation, oxidation, and the two shifts worth memorising” — Explainers, 20 Jan 2024
You state that fourteen of twenty suppliers report an MS identity test. Does that count reports supplied to you on request, or only what appears on the certificate a customer receives?
— D. Lockridge, Tulsa, OK
The former, which the table note now says explicitly. The count for what appears on a customer-facing certificate is lower in at least four cases, and we should have separated the two columns rather than merging them.
On “Deamidation, oxidation, and the two shifts worth memorising” — Explainers, 20 Jan 2024
Sixteen years in a peptide plant and I have never once been asked by a customer which ionisation source we used. I have been asked hundreds of times for a purity figure to one more decimal place.
— M. Tsvangirai, Bulawayo
On “Deamidation, oxidation, and the two shifts worth memorising” — Explainers, 20 Jan 2024
The claim that a reproduced spectrum is worth more than any number in the document seems overstated. Most buyers cannot read a spectrum, and a printed image invites false confidence rather than scrutiny.
— Y. Sasaki, Sapporo
Partly conceded. A spectrum is worth more to a reader who can read one, and this department exists partly to increase that number. But it is also an artefact that can be checked by a third party later, which a bare verdict is not, and that alone justifies printing it.
On “The badge economy, and what it is actually certifying” — The Ledger, 19 Jan 2024
On the archive point: a public record of submissions by vendor would be gamed within a month. Vendors would submit under the names of resellers, or through intermediaries, and the archive would show a distribution as selected as the current one but with a veneer of completeness.
— Y. Sasaki, Sapporo
Probably true in part, and it is the strongest argument against our proposal. Our answer is that gaming requires effort and leaves traces, which the present arrangement does not, and that a partially gamed record is more informative than no record. We would not claim more than that.
On “The badge economy, and what it is actually certifying” — The Ledger, 19 Jan 2024
VendorInvestigate does not measure anything and you have grouped it with three laboratories under the heading independent testing. That is exactly the conflation your article says the market makes.
— M. Tsvangirai, Bulawayo
A fair hit. The tag under which this coverage sits predates the distinction we now draw, and we have added the distinction to the second paragraph and to the table. The department name will follow at the next reorganisation of the site.
On “The badge economy, and what it is actually certifying” — The Ledger, 19 Jan 2024
The price table is the most useful thing you have published this year and also the thing most likely to be quoted out of context by somebody selling a comparison service. You might consider a note.
— D. Lockridge, Tulsa, OK
There is one, and we have strengthened it. The figures are what this publication was invoiced at list rates and are not quotations a reader should expect; volume submitters pay materially less.
On “The badge economy, and what it is actually certifying” — The Ledger, 19 Jan 2024
You note that no service offers sterility testing and that it takes fourteen days. Worth saying more plainly: a purity certificate and a sterility assurance are not merely different tests, they are different disciplines with different facilities, and no amount of chromatography will ever bear on it.
— T. Wexford, Louisville, KY
Correct and worth the emphasis. We have said it in the certificates piece and should say it here too: nothing any of these four services sells addresses sterility, endotoxin or container closure integrity, and no combination of their reports adds up to one.
On “The badge economy, and what it is actually certifying” — The Ledger, 19 Jan 2024
I run analytical services and I object to the framing of your blind comparison. You bought our cheapest tier, published the number it produced alongside a competitor’s most thorough package, and called the result a spread. It is not a spread. It is three different products, priced accordingly, and your own table says so two columns to the right of the headline figure.
— R. Cadogan, Bridgetown
This is the objection we thought was most likely and we think it is partly right. The comparison is of standard products at standard prices, which is what buyers actually purchase, and we said so. But the presentation invites the reading you object to, and the figure caption now states the tier alongside each result rather than leaving it to the method columns.
On “What the older diet-and-exercise trials found in the hip” — Clinical Trials, 17 Jan 2024
Three vendors have now sent me marketing material claiming their product preserves lean mass during GLP-1 treatment, two of them citing your publication as a source for the underlying composition figures. You may want to know that.
— K. Mwangi, Nakuru
We did not, and we are grateful. Quoting our reporting of a substudy alongside an unevidenced product claim is a misuse of it, and the standards desk has written to all three.
On “What the older diet-and-exercise trials found in the hip” — Clinical Trials, 17 Jan 2024
I have read your protein tables twice and I still cannot work out what I should eat. I appreciate that this is the honest position but it is not a useful one for a person in a supermarket.
— D. Ó Súilleabháin, Killarney
It is a fair complaint about a real limitation. What we can say is that the defensible range is narrower than the disagreement suggests, that the denominator matters more than the ratio, and that a clinician or dietitian can convert a range into a number for your body in a way that a magazine cannot.
On “What “LC-MS: conforms” tells a reader, which is almost nothing” — Laboratory Notebook, 16 Jan 2024
Sixteen years in a peptide plant and I have never once been asked by a customer which ionisation source we used. I have been asked hundreds of times for a purity figure to one more decimal place.
— E. Adamou, Nicosia
On “What “LC-MS: conforms” tells a reader, which is almost nothing” — Laboratory Notebook, 16 Jan 2024
The claim that a reproduced spectrum is worth more than any number in the document seems overstated. Most buyers cannot read a spectrum, and a printed image invites false confidence rather than scrutiny.
— G. Kalinowski, Poznań
Partly conceded. A spectrum is worth more to a reader who can read one, and this department exists partly to increase that number. But it is also an artefact that can be checked by a third party later, which a bare verdict is not, and that alone justifies printing it.
On “What “LC-MS: conforms” tells a reader, which is almost nothing” — Laboratory Notebook, 16 Jan 2024
A small defence of the linear MALDI instrument. It is fast, it tolerates dirty samples, and for a synthesis chemist checking that a chain has grown by the residue intended it is entirely fit for purpose. The problem is not the instrument. It is printing its output on a release document.
— S. Rajapaksa, Colombo
This is the same objection a reader made about the twelve-minute purity gradient two years ago, and it was right then as well. The criticism is of the use, not the tool.