The near totality of human mate choice research occurs in large-scale, urban, industrial populations. It is unclear to what extent lessons learned from such populations reflect generalizable features of human mating psychology as opposed to localized responses to the demands of these historically unusual environments. Here, we use couple simulation, an agent-based modeling technique, to compare models of mate choice across both a U.S. sample (n = 1678) and a sample of k = 15 couples from Conambo, Ecuador—a relatively remote community of horticultural-foragers in the Ecuadorian Amazon. The Conambo sample provides a unique opportunity to evaluate models of mate choice in that (1) this sample represents approximately 50% of the households within this community and (2) all of the participants in this sample are acquainted with one another. Participants in Conambo completed a ranking task in which each participant ranked each opposite-sex adult in the community in terms of their quality as a spouse. We used these rankings to simulate the mating market in Conambo under alternative models of mate choice. We find that these models are able to reproduce Conambo marriages at a high degree of accuracy and perform comparably across both the Conambo sample and U.S. samples. Specifically, the resource allocation model performs best in reproducing mate choices in both the U.S. and Conambo samples. These results suggest that at least some aspects of human mating psychology generalize across both large-scale industrialized and small-scale populations.

We present a study testing the existence and correlates of personality concepts in the village of Conambo, Ecuador, which is home to horticultural-foragers located in the Sápara Territory of the Ecuadorian Amazon. Lexical terms to describe the three focal personality concepts from the HEXACO taxonomy—Sociability, Immodesty, and Un-emotionality—were interpreted from Spanish into the Indigenous languages of Achuar and Quichua. These terms were employed in a photo ranking task wherein 76 adult community members ranked the relative standing of same-sex others on each personality concept. Inter-ranker agreement was high for Sociability and Immodesty, but low for Un-emotionality. We tested the associations among individual differences in (i) Sociability and Immodesty, (ii) hierarchical status and fertility, which are hypothesized fitness-linked benefits of high Sociability and Immodesty, and (iii) physical strength, which is a hypothesized calibrator of status-oriented personality strategies. Using Bayesian models and psychological networks including age controls, we found good evidence that men's physical strength associated positively with Sociability, Immodesty, and status. Among both sexes, Sociability and Immodesty exhibited strong positive correlations with status, but evidence was weaker that the personality traits associated with fertility. Status associated positively with fertility among both sexes. We conclude that two personality concepts imported from the HEXACO and Big Five taxonomies, Sociability and Immodesty, exist with common meaning in the minds of Conambo villagers and appear adaptively patterned in relation to physical strength and fitness-linked outcomes. We argue that the photo ranking task employed in this research produces personality assessments with high validity and should therefore be adopted in future studies of individual differences in face-to-face groups.

A table-top microdevice was introduced in this work to produce ultrasmall particles for drug delivery via inhalation. The design and operation are similar to that of spray-drying equipment used in industry, but the device itself is much smaller and more portable in size, simpler to operate and more economical. More importantly, the device enables more accurate control over particle size. Using Flavopiridol, an anti-inflammation medication, formulations have been developed to produce inhalable particles for pulmonary delivery. A solution containing the desired components forms droplets by passing through an array of micro-apertures that vibrate via a piezo-electrical driver. High-purity nitrogen gas was introduced and flew through the designed path, which included the funnel collection and cyclone chamber, and finally was pumped away. The gas carried and dried the micronized liquid droplets along the pathway, leading to the precipitation of dry solid microparticles. The formation of the cyclone was essential to assure the sufficient travel path length of the liquid droplets to allow drying. Synthesis parameters were optimized to produce microparticles, whose morphology, size, physio-chemical properties, and release profiles met the criteria for inhalation. Bioactivity assays have revealed a high degree of anti-inflammation. The above-mentioned approach enabled the production of inhalable particles in research laboratories in general, using the simple table-top microdevice. The microparticles enable the inhalable delivery of anti-inflammation medicine to the lungs, thus providing treatment for diseases such as pulmonary fibrosis and COVID-19.

When interacting with infants, humans often alter their speech and song in ways thought to support communication. Theories of human child-rearing, informed by data on vocal signalling across species, predict that such alterations should appear globally. Here, we show acoustic differences between infant-directed and adult-directed vocalizations across cultures. We collected 1,615 recordings of infant- and adult-directed speech and song produced by 410 people in 21 urban, rural and small-scale societies. Infant-directedness was reliably classified from acoustic features only, with acoustic profiles of infant-directedness differing across language and music but in consistent fashions. We then studied listener sensitivity to these acoustic features. We played the recordings to 51,065 people from 187 countries, recruited via an English-language website, who guessed whether each vocalization was infant-directed. Their intuitions were more accurate than chance, predictable in part by common sets of acoustic features and robust to the effects of linguistic relatedness between vocalizer and listener. These findings inform hypotheses of the psychological functions and evolution of human communication. Across 21 societies, people alter their speech and song when interacting with infants. These infant-directed vocalizations are recognized by listeners. This suggests that forms of human vocalizations may be shaped by their functions.

501 inhaled insulin (INH) is a novel liquid formulation of human insulin for inhalation with faster onset of action than s.c. insulin lispro (LIS). This randomized, replicated cross-over trial investigated the variability of INH vs. LIS during 10-hour glucose clamps in non-smoking subjects with T1D. Fourteen subjects (age [mean±SD] 32.5±7.9 years, BMI 26.5±2.1 kg/m2, HbA1c 7.5±0.8 %) received 2 single doses of 92.2 IU INH via the Afina inhaler (n=13 completing subjects) and 2 injections of an equivalent 12 U LIS dose (n=12). The inhalations were performed by the subjects after a brief training on the correct inhalation technique; injections were given by trained staff. Repeated dosing of INH by the same subject resulted in reproducible insulin absorption and insulin action, with lower or similar variability vs. LIS (Table 1). The response to INH between subjects was more variable than for LIS. The 13.8±8.1% mean relative biopotency of INH was consistent with previous findings. INH was well tolerated, adverse events (8 with INH, 13 with LIS) were mild to moderate in severity. No cough and no acute changes in spirometry were observed with any inhalation. In conclusion, the intra-individual response to self-administration of 501 inhaled insulin is as reproducible as that of s.c. insulin lispro injected by experienced staff. This is a clinically meaningful outcome and enables individual dose titration of 501 insulin in future treatment. Disclosure E. Zijlstra: Employee; Self; Profil. Speaker’s Bureau; Self; Aerami Therapeutics, Eli Lilly and Company, Novo Nordisk A/S. G. Andersen: Employee; Self; Profil Institute for Clinical Research. L. Plum-Moerschel: Other Relationship; Self; Eli Lilly and Company, Novo Nordisk A/S. M. Rhodes: None. R. Patton: None. B. Bueche: None. M. Kuo: None. T.H. Le: None. B.J. Stedman: None. J.S. Patton: Board Member; Self; Dance Biopharm Holdings, Inc.

ABSTRACT Recent research has elucidated many factors which play a role in the development and composition of human microbiomes. In this study we briefly examine the microbiomes of saliva and fecal samples from 71 indigenous individuals, and chicha samples from 28 single family households in a remote community in the Ecuadorian Amazon. Fecal and saliva samples were collected at two separate time points whereas chicha samples were collected at four time points, once each day of the fermentation process. In total 324 samples were collected: 113 saliva, 108 chicha, and 103 fecal. Microbial composition and diversity were assessed using shotgun metagenome sequence data. Chicha samples were found to be nearly entirely composed of the order Lactobacillales , accounting for 90.1% of the relative abundance. Saliva samples also contained a high relative abundance of Lactobacillales (31.9%) as well as being composed of Neisseriales (12.8%), Actinomycineae (8.7%), Bacteroidales (7.0%), Clostridiales (6.8%), Micrococcineae (6.5%), and Pasteurellales (6.0%). Fecal samples were largely composed of the three orders Clostridiales (33.7%), Bacteroidales (21.9%), and Bifidobacteriales (16.5%). Comparison of α-diversity, as calculated by Shannon’s Diversity Index, in mothers and their offspring showed no significant difference between the two groups in either fecal or saliva samples. Comparison of β-diversity in fecal and saliva samples, as calculated by the Bray-Curtis Dissimilarity measure, within household units and between differing households showed that members of the same household were significantly less dissimilar to each other than to members of other households in the community. Average microbiome composition for individuals within fecal and saliva samples was assessed to determine the impact of an individual’s household on the composition of their microbiome. Household was determined to have a significant impact on both fecal and oral microbiome compositions.

Dance 501 is a novel liquid formulation of human insulin for inhalation with the Dance 501 inhaler. This randomized, cross-over trial investigated the pharmacodynamic (PD) action and safety of INH in its final formulation vs. LIS during 10-hour glucose clamps in non-smoking subjects with T2D. LIS was injected s.c. at low (12 U), medium (24 U) and high (48 U) doses, INH was inhaled at equivalent doses, assuming a 13% relative biopotency. Twenty-two subjects completed all 6 single dose administrations. INH and LIS demonstrated a linear dose-response relationship and comparable total PD action (AUC_GIR0-10h). Median relative biopotency of INH was 12.3 to 13.0%. PD profiles (Figure) show a more rapid onset of action for equivalent doses of INH vs. LIS (median differences 6.5 to 20 min, p<0.02) and greater action in the first hour after administration (median differences 19.7 to 48.2 mg/kg, p<0.05). No safety issues and no cough were observed with any inhalation. These results nicely confirm and extend to higher doses the results of a previous PK/PD study in type 2 patients with an earlier version of the Dance 501 device and formulation (Zijlstra et al. Diabetes 2015; 64(Suppl 1): A248). In conclusion, Dance 501 showed favorable glucodynamic properties vs. LIS and excellent tolerability and may therefore become a clinically meaningful alternative to rapid-acting insulin injectables. Disclosure E. Zijlstra: Speaker's Bureau; Self; Novo Nordisk A/S. L. Plum-Moerschel: None. M. Ermer: None. O. Klein: None. L. Porter: Other Relationship; Self; Dance Biopharm Holdings Inc., Eiger BioPharmaceuticals. B. Bueche: Employee; Self; Dance Biopharm Holdings Inc. M. Kuo: Employee; Self; Dance Biopharm Holdings Inc. T. Le: None. B.J. Stedman: None. J.S. Patton: Other Relationship; Self; Dance Biopharm Holdings Inc. Funding Dance Biopharm Holdings Inc.

The design development of a small, hand held, battery operated, breath actuated inhaler as a drug/device platform for inhaled insulin posed a number of technical challenges. Our goal was to optimize lung deposition and distribution with aerosol generators producing 3–6 μm particle size distribution.

Letter to the EditorResponse to paper by Singh et al. “Hyperinsulinemia adversely affects lung structure and function”Ronald K. Wolff, Joseph D. Brain, John S. Patton, and Denny LiggittRonald K. WolffRK Wolff-Safety Consulting Inc., Fort Myers, Florida; , Joseph D. BrainMolecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts; , John S. PattonDance Biopharm Holdings Inc., Brisbane, California; and , and Denny LiggittDepartment of Comparative Medicine, School of Medicine, University of Washington, Seattle, WashingtonPublished Online:12 Jul 2016https://doi.org/10.1152/ajplung.00187.2016MoreSectionsPDF (53 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat to the editor: We have serious concerns regarding the recently published paper by Singh et al. (16), which states, “Our work has important general implications that should hopefully lead to questioning of many current trends or practices including use of inhaled insulin formulations in diabetes.” This conclusion is not supported as evidenced by 1) the technical limitations in the experiments described in the paper and 2) the omission of abundant pertinent data that is neither referenced nor discussed. The pulmonary effects of inhaled insulin in both patients and animals have been well described in the literature and show minimal effects. These peer-reviewed papers are absent in the Singh paper. In summary, this paper applies poorly designed experiments in mice to humans, ignoring decades of relevant research. Below, we detail the major deficiencies. Importantly, we believe it is irresponsible to use the data in the Singh et al. paper as the foundation for giving advice to physicians and their patients.Technical LimitationsThe focus of this paper is the possible pulmonary effects of insulin delivered to the lungs. However, the method used in this paper is an inefficient and imprecise way of achieving pulmonary dosing. They do not use inhalation, and they don't even use intratracheal instillation (IT). Many labs, including that of one of us [Brain et al. (1)] routinely employ intratracheal instillations in 20-g mice. With nasal instillation as is used in the experiments reported by Singh et al. (16), little of the instilled material may get into the lungs when volumes are small. As the volume of the instilled solution increases, an increasing but variable fraction is aspirated into the lungs (17). In this paper, no information is given that tells us the fraction of the intranasal dose that actually reaches the lungs. They also fail to tell us the instilled volume. The fact that the insulin dose was very high and the animals did not die of hypoglycemia suggests that much of the “delivered dose” was probably swallowed and digested.The anatomic distribution of particles in the lungs differs following instillation vs. inhalation. Brain et al. (1) and Foster et al. (4) have clearly shown that delivery methods to the lungs of rodents, other than inhalation, give rise to considerably different deposition results. The methods used by Singh et al. for intranasal administration are not described, and they should be presented. Southam et al. (17) have shown large variations in lung deposition depending on intranasal technique.It is important to recognize that the liquid solution used to deliver the insulin was an acid, pH 2 (0.01 N HCl). Not only is insulin unstable at this pH but the major acidic degradation products, covalent dimers, are the most immunogenic degradation products from insulin. More importantly, acid aerosols of pH 2 have been clearly shown to have adverse effects in both humans (8) and animals (14). Respiratory complications of gastroesophageal reflux are well known and may have influenced results. Use of this inappropriate vehicle may have influenced the results. In addition, 0.01 N HCl is hypotonic. Hypotonic solutions can cause damage and bursting of epithelial cells. Instillations should always be isotonic.Essential controls are missing from the experimental design. The “controls” they describe are animals that were given the vehicle, 0.01 normal hydrochloric acid (pH 2). We believe that 11 daily sequential anesthesias and instillations of acid into the nose, pharynx, and lungs had effects on both of the two groups studied. Conspicuous by its absence is a necessary third group, a true control. We regard this omission of animals that received neither of these two treatments as a serious flaw. They compare the acid vehicle only with the vehicle plus insulin. We suspect that these repeated nasal instillations affected the entire physiology of the mice. For example, what were the changes in body weight over the study period? We predict that this harsh treatment would result in loss of body weight, but we don't know since there is no true control.The histopathology as presented in the paper is very difficult to interpret and the interpretations are of concern based on the following comments.The materials and methods does not provide adequate description of the methods used for fixation of the lungs, which is critical when trying to make statements about changes in lung structure. We had to go back through two references to any mention on the protocols used for fixation and even then the description is minimal. When defining changes to lung structure it would be hoped that the authors would follow the guidelines set out by the ATS for fixation of lung tissue [Hsia CC et al., ATS/ERS Joint Task Force on Quantitative Assessment of Lung Structure (5)].There is not a quantitative nor semiquantitative evaluation of the lesions presented. With the advances in digital imaging and imaging software one would expect that some type of quantitative analysis be performed to remove bias from the data present. There are concerns over the data presented due to the following observations of the work presented in this manuscript:1) The photos are of such a low power that they cannot be evaluated from the publication and descriptions or observations are vaguely described. For instance a PAS stain is provided to show goblet cells, however, Alcian blue-should also have been used.2) There is a claim of peribronchial collagen production, but appearance of true collagen in 12 days seems unrealistic.3) The presence of smooth muscle in the normal mouse lung is to be expected and depends on what areas of the lung are sampled (18). Also nonuniform distribution of insulin from the instillation procedure could have influenced results. Therefore, the authors would need to perform uniform random sampling of the lungs and images acquired to accurately interpret findings from these studies. The importance of performing adequate sampling of airways for inhaled toxicants is provided by Dallas Hyde et al. (6).4) Tissue quantitation can be influenced heavily by what parts of the lung are examined since if too much of the upper airway or mediastinum is included native collagen levels can skew measurements. Selective histological examination can compromise outcomes and the lack of an appropriate control group can make interpretation uncertain. The β-catenin knockdown data are also difficult to interpret. Singh et al. (16) do not describe the carrier system used to deliver the siRNA. This is problematic since most of these carriers (typically lipids) are associated with enhancing siRNA-mediated innate inflammatory, which can confound findings and must be appropriately controlled (10).The dose of insulin used, 50 μg, is high and of limited relevance to human clinical use. The 50-μg dose in a mouse of typical body weight of 25 g is 2 μg/g, or 2 mg/kg. This dose is approximately threefold higher than the deposited lung dose of 0.6 mg/kg insulin that was found to be without effects on lung histopathology following 6 mo of inhalation exposure in rats (2). It is also 13-fold higher than the 0.15 mg/kg insulin lung dose estimated for mean human use for Exubera (2). The 0.15 mg/kg dose is the nominal capsule dose delivered to humans, while the lung deposited dose is ∼0.05-0.07 mg/kg or 30- to 40-fold less than the mouse lung dose. Thus the Singh experiments are at doses that would not be achieved in human use. Rodents metabolize insulin more quickly than humans and so much higher lung doses can be achieved in rodents compared with humans. We also note the absence of any information about the grade of the Sigma human recombinant insulin used.Pertinent Animal and Human DataThe paper by Singh et al. (16) omits reference to the considerable body of information relating to the pulmonary safety of inhaled insulin in patients and animals. Extensive clinical data with inhaled insulin provides the most relevant information. Pfizer's inhaled insulin product (Exubera) was approved by both the FDA and the EU. This was based on more than a decade of experiments and studies of thousands of patients. Bronchopulmonary lavage after 3 mo of inhaled prandial insulin showed no inflammatory markers (7) in the face of measured higher levels of insulin (9). Eli Lilly and Novo Nordisk also have extensive clinical experience similar to that of Exubera (15). Finally, more recently, Mannkind's inhaled insulin (Afrezza) was approved by the FDA and it is currently being marketed. For both approved drugs large amounts of data were submitted, reviewed, and formed the basis of a positive FDA decision.The review paper by Siekmeier and Scheuch (15) lists results from 20 clinical trials that studied the safety of inhaled insulin. In none of the studies were there any findings of clinical significance. In one of the largest trials, a 2-year study of Exubera (13), it was stated that “Small, clinically non-meaningful treatment group differences in the change in FEV1 during the first 3 mo of treatment were found. Most notably, the between-group differences did not increase after 3 mo for up to 2 years, and pulmonary function declined at similar rates in both groups during months 3 to 24.” Additional clinical information has also become available since the Siekmeier and Scheuch (15) review primarily on Afrezza with similar results (11). The only clinically relevant negative pulmonary finding in patients has been bronchospasm in individuals with asthma/COPD with Afrezza (3), which appears to be related to the fumaryl diketopiperazine excipient specific to the Afrezza formulation. Also, Singh et al. (16) reported data suggesting an increase in airway hyperresponsiveness in rats, whereas clinical data with another inhaled growth factor promoter, human growth hormone, showed no change in airway hyperresponsiveness in individuals with asthma (10).Singh et al. (16) also failed to refer to the information from long-term 6-mo toxicity studies of inhaled insulin in rats and monkeys (2) and in dogs (19) at lung deposited doses of 0.6 mg/kg, 0.15 mg/kg, and 0.18 mg/kg, the maximum tolerated doses in these respective species. All of these studies conducted using the appropriate administration method of inhalation delivery showed no effects on pulmonary function or lung histopathology.The study reported by Singh et al. has many technical limitations and was conducted at doses not relevant to human inhalation delivery. These facts should be considered as well as the overwhelming clinical evidence at relevant doses and the appropriate inhalation delivery route that shows inhaled insulin poses minimal risks to patients with diabetes while offering the possibility that patient preference for inhalation translates to better compliance and improved outcomes.DISCLOSURESR. K. Wolff worked many years on the development of inhaled insulin, consultant for Dance Biopharm (see below). J. D. Brain worked for many years as consultant for companies developing inhaled insulin including Inhale/Nektar, Mankind and Dance. J. S. Patton declares 25 years working on development of inhaled insulin at Inhale Therapeutics/Nektar Therapeutics (Cofounder, CSO) and Dance Biopharma Holdings Inc. (Founder, CEO). D. Liggitt declares no conflicts.AUTHOR CONTRIBUTIONSR.W., J.D.B., J.P., and D.L. analyzed data; R.W., J.D.B., J.P., and D.L. interpreted results of experiments; R.W., J.D.B., J.P., and D.L. drafted manuscript; R.W., J.D.B., J.P., and D.L. edited and revised manuscript; R.W., J.D.B., J.P., and D.L. approved final version of manuscript.REFERENCES1. Brain JD, Knudson DE, Sorokin SP, Davis MA. Pulmonary distribution of particles given by intratracheal instillation or by aerosol inhalation. Environ Res 11: 13–33, 1976.Crossref | PubMed | ISI | Google Scholar2. FDA. Pharmacological/Toxicological Evaluation — Exubera, NDA 21-868. http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4169B1_02_04-FDA-ClinPharm-Toxicology.pdf. 2005.Google Scholar3. FDA. Medical Review — Afrezza, NDA 22-472. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/022472Orig1s000MedR.pdf. 2014.Google Scholar4. Foster WM, Walters DM, Longphre M, Macri K, Miller LM. Methodology for the measurement of mucociliary clearance in the mouse by scintigraphy. J Appl Physiol 90: 1111–1118, 2001.Link | ISI | Google Scholar5. Hsia CC, Hyde DM, Ochs M, Weibel ER; ATS/ERS. Joint Task Force on Quantitative Assessment of Lung Structure. An official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am J Respir Crit Care Med 181: 394–418, 2010.Crossref | PubMed | ISI | Google Scholar6. Hyde DM, Harkema JR, Tyler NK, Plopper CG. Design-based sampling and quantitation of the respiratory airways. 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Comparative biological potency of acidic sulfate aerosols: implications for the interpretation of laboratory and field studies. Environ Res 65: 69–85, 1994.Crossref | PubMed | ISI | Google Scholar15. Siekmeier R, Scheuch G. Inhaled insulin — does it become reality? J Physiol Pharmacol 59, Suppl 6: 81–113, 2008.PubMed | ISI | Google Scholar16. Singh S, Bodas M, Bhatraju NK, Pattnaik B, Gheware A, Parameswaran PK, Thompson M, Freeman M, Mabalirajan U, Gosens B, Pabelick C, Linneberg A, Prakash YS, Agrawal A. Hyperinsulinemia adversely affects lung structure and function. Am J Physiol Lung Cell Mol Physiol 310: L837–L845, 2016.Link | ISI | Google Scholar17. Southam DS, Dolovich M, O'Byrne PM, Inman MD. Distribution of intranasal instillations in mice: effects of volume, time, body position, and anesthesia. Am J Physiol Lung Cell Mol Physiol 282: L833–L839, 2002.Link | ISI | Google Scholar18. Suarez CJ, Dintzis SM, Frevert CW. Respiratory. In: Comparative Anatomy and Histology: A Mouse and Human Atlas, edited by Treuting PM, Dintzis SM, Frevert C, Liggitt D, Montine KS. Amsterdam: Elsevier Academic, 2012, chapt. 9, p. 121–134.Crossref | Google Scholar19. Vick A, Wolff R, Koester A, Reams R, Deaver D, Heidel S. A 6-month inhalation study to characterize the toxicity, pharmacokinetics, and pharmacodynamics of human insulin inhalation powder (HIIP) in beagle dogs. J Aerosol Med 20: 112–126, 2007.Crossref | PubMed | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: R. K. Wolff, RK Wolff-Safety Consulting Inc., 14931 Reflection Key Circle, #722, Fort Myers, FL 33907 (e-mail: [email protected]com). Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Collections Cited ByAuthor response to letter to editor: Hyperinsulinemia adversely affects lung structure and functionSuchita Singh, Manish Bodas, Naveen K. Bhatraju, Bijay Pattnaik, Atish Gheware, Praveen Kolumam Parameswaran, Michael Thompson, Michelle Freeman, Ulaganathan Mabalirajan, Reinoud Gosens, Balaram Ghosh, Christina Pabelick, Allan Linneberg, Y. S. Prakash, and Anurag Agrawal12 July 2016 | American Journal of Physiology-Lung Cellular and Molecular Physiology, Vol. 311, No. 1 Press Release E-cigarette Use during Pregnancy Creates Lung Dysfunction in Babies - December 8, 2022 More from this issue > Volume 311Issue 1July 2016Pages L180-L182 Copyright & PermissionsCopyright © 2016 the American Physiological Societyhttps://doi.org/10.1152/ajplung.00187.2016PubMed27407081History Received 10 May 2016 Accepted 1 June 2016 Published online 12 July 2016 Published in print 1 July 2016 Metrics