Every letter we have printed
Page 77 of 77 of this archive, newest first.
On “Forty-four per cent: reading the nausea figure properly” — Pharmacology, 6 Jan 2024
A small point of precision. You use "gastroparesis" in the tag list and then spend a paragraph saying it is not a synonym for drug-induced emptying delay. That is a slightly awkward position to hold.
— J. Vasilenko, Chisinau
It is, and it is a compromise with how readers search. The tag exists because that is the word people use; the glossary exists because it is the wrong one. We would rather be findable and then precise than precise and unread.
On “From vial to bench: what is recorded and what is assumed” — The Supply Chain, 6 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.
— R. Anand, Pune
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 “From vial to bench: what is recorded and what is assumed” — The Supply Chain, 6 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 Real behaviour is surely more complicated: a supplier might publish a poor result on a batch it has withdrawn, or publish everything for a period to establish credibility and then stop.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.
— C. Adeoti, Ibadan
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 “From vial to bench: what is recorded and what is assumed” — The Supply Chain, 6 Jan 2024
Your suggestion that laboratories publish the fact of a submission while keeping the result confidential is the first proposal I have read in this area that a laboratory could actually implement without breaching a client obligation. I have raised it internally.
— P. Kovalenko, Lviv
We would be glad to report the outcome either way, including if the answer is no and the reason is commercial. The proposal is only useful if somebody adopts it, and a published refusal is more informative than silence.
On “From vial to bench: what is recorded and what is assumed” — The Supply Chain, 6 Jan 2024
You disclose that two of these services advertise with you and then spend four thousand words on structural criticism of the sector they operate in. I cannot decide whether that is admirable independence or an elaborate way of appearing independent. Probably the former. I wanted to say that I noticed the question.
— D. Ramkissoon, Port of Spain
So do we, every time this department writes about the sector. The only answers we have are procedural: the disclosure, the standards desk edit, the consulting prohibition on the writer, and the practice of printing objections like yours unedited.
On “Attribution is the hard part” — Explainers, 5 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.
— N. Fairweather, Hamilton
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 “Attribution is the hard part” — Explainers, 5 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?
— M. Karlsen, Kristiansand
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 “Why a 0.036-dalton difference is the hardest number in peptide identity” — Laboratory Notebook, 4 Jan 2024
I have spent a week trying to reconcile a certificate’s stated mass of 4113.6 with a figure of 4111.1 I calculated from the sequence, and had convinced myself something was wrong with the vial. It was the isotope convention. Thank you, and also: how is this not stated on every certificate in existence?
— A. Basaraba, Winnipeg, MB
We wish we knew. It is the single most common source of spurious discrepancies reaching this desk, it costs nothing to state, and we have now asked all twenty companies in the dossier programme to add it. Three have.
On “Why a 0.036-dalton difference is the hardest number in peptide identity” — Laboratory Notebook, 4 Jan 2024
You write that leucine and isoleucine cannot be distinguished by tandem mass spectrometry. That is too absolute. Side-chain fragmentation under high-energy conditions produces diagnostic w and d ions, and the discrimination has been demonstrated repeatedly.
— P. McAlinden, Belfast
Correct, and the text has been amended. The discrimination is achievable under specialised conditions and is not available in any routine service this market uses, which is what we should have written rather than the stronger claim.
On “Why a 0.036-dalton difference is the hardest number in peptide identity” — Laboratory Notebook, 4 Jan 2024
I would add one omission to your six lines: the date and nature of the last calibration. A parts-per-million figure from an instrument last calibrated a fortnight ago is a different claim from one calibrated that morning with an internal standard.
— D. Chukwuma, Onitsha
Agreed, and it may be the best suggestion we have received on this subject. It is now a seventh line in the version of the list we send to suppliers, with the note that internal calibration should be stated where it was used.
On “Why a 0.036-dalton difference is the hardest number in peptide identity” — Laboratory Notebook, 4 Jan 2024
Your article says a matching mass does not confirm a sequence, which is correct, and then rather implies that vendors are trading on the ambiguity. I run analytical services and I would put it differently: we report what we measured, in the words our clients ask for. If the Journal wants the word confirmed retired, write to the buyers, not to us.
— M. Sandhu, Amritsar
That is a fair reallocation of the criticism and we accept it. The word is chosen by whoever commissions the report, and laboratories are answering the question they were paid to answer. Our complaint is with the practice, not with the analysts, and the article should have located it more precisely.
On “Everything on the page, in the order a chemist would read it” — The Supply Chain, 3 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. Zangwill, Manchester
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 “Everything on the page, in the order a chemist would read it” — The Supply Chain, 3 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.
— N. Villaseñor, Guadalajara
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 tolerability data everybody quotes and nobody reads” — Pharmacology, 1 Jan 2024
I want to push back on the ginger paragraph. You describe the evidence as transferred from pregnancy and chemotherapy, which is accurate, and then include it in the table anyway. Either it belongs or it does not.
— E. Marchetti, Bologna
It belongs, labelled. The table is a map of what is recommended and on what basis, not a list of endorsements, and excluding widely used low-risk measures because their evidence is transferred would make the map less useful rather than more honest. We have made the column heading clearer.
On “The tolerability data everybody quotes and nobody reads” — Pharmacology, 1 Jan 2024
Your figures show diarrhoea at thirty-two per cent and constipation at twenty-three per cent in the same trial arm. I assumed one of these was an error until your mechanism section. It would be worth putting that explanation before the table rather than after it.
— H. Ravensworth, York