Rebuttal by Richard J. A. Wilson and Trevor A. Day
Notice bibliographique
Résumé
Our colleagues skillfully addressed how peripheral chemoreceptors interact with systemic effects of CO2. Unfortunately, systemic CO2 affects oxyhaemoglobin dissociation, sympathetic, endocrine and cardiovascular systems, and afferents from lungs and CO2-sensitive upper airway receptors – all capable of having effects on ventilation independent of central chemoreceptors. Duffin's ingenious rebreathing studies add further concerns, namely psychological and physiological aspects of voluntary hyperventilation (e.g. Steinback et al. 2011). Similarly, carotid body denervation (CBD) studies acclaimed by Teppema & Smith (2013) introduce complications including disruption of baroreflex, abolition of central carotid body regulation of sympathetic and parasympathetic outputs, and unknown contribution of changes associated with long-term plasticity. To mitigate these issues, we developed an artificially perfused rat preparation devoid of intact autonomic and respiratory feedback loops, descending and vagal influences (Day & Wilson, 2009). Demonstrations of hypoadditivity in our preparation are reconcilable with work in humans summarized by Duffin & Mateika (2013). While Duffin & Mateika favour the conclusion of additive interactions, simple addition in ventilation mathematically necessitates hypoadditivity in frequency and/or tidal volume (Mitchell, 1990). Moreover, stimulus and state specific parcelling of responses into frequency and tidal volume suggests hypoadditivity translates to ventilation in certain circumstances. However, our findings are not easily reconciled with a hyperadditive system, as argued by Teppema & Smith (2013). So how do we move forward? Pigeonholed discussions addressing the nature of interaction have illustrated the importance of type, magnitude, order and pattern of stimulus, and species and preparation used, but have yet to reconcile hypoadditive and hyperadditive camps. Therefore, we suggest the need for a new paradigm: a hybrid model incorporating multiple forms of interaction depending on systemic CO2 and/or physiological state. In support of this new paradigm, we note (a) even the hyperadditive O2–CO2 carotid body interaction transitions to hypoadditive at severe levels (Fitzgerald & Parks, 1971), (b) the additive-to-hyperadditive transition with long term facilitation cited by Duffin & Mateika (2013), and (c) Hodges et al. (2005), cited by Teppema & Smith (2013), is only partly consistent with hyperadditivity. Hodges et al. show that, while both mild and severe hypercapnic brainstem aCSF cause increased ventilation, only responses to severe hypercapnic aCSF were reduced by CBD. Thus, while Teppema & Smith considered only the blunted responses to severe hypercapnic aCSF, lack of CBD effect on responses to mild hypercapnic aCSF argues for hypoadditivity. These data are therefore consistent with a hybrid system that endows respiratory chemosensitivity with redundancy and a large dynamic range. Readers are invited to give their views on this and the accompanying CrossTalk articles in this issue by submitting a brief comment. Comments may be posted up to 6 weeks after publication of the article, at which point the discussion will close and authors will be invited to submit a ‘final word'. To submit a comment, go to http://jp.physoc.org/letters/submit/jphysiol;591/18/4365 This work was supported by Alberta Innovates-Health Solutions and Canadian Institutes of Health Research (R.J.A.W.) and a Mount Royal University sabbatical (T.A.D.). Neither author has conflicts to disclose. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,014 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,002 | 0,004 |
| Communication savante | 0,004 | 0,004 |
| Science ouverte | 0,003 | 0,002 |
| Intégrité de la recherche | 0,011 | 0,020 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,065 | 0,099 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».