Mechanisms maintaining right ventricular contractility-to-pulmonary arterial elastance ratio in VA ECMO: a retrospective animal data analysis of RV-PA coupling.

BACKGROUND: To optimize right ventricular-pulmonary coupling during veno-arterial (VA) ECMO weaning, inotropes, vasopressors and/or vasodilators are used to change right ventricular (RV) function (contractility) and pulmonary artery (PA) elastance (afterload). RV-PA coupling is the ratio between right ventricular contractility and pulmonary vascular elastance and as such, is a measure of optimized crosstalk between ventricle and vasculature. Little is known about the physiology of RV-PA coupling during VA ECMO. This study describes adaptive mechanisms for maintaining RV-PA coupling resulting from changing pre- and afterload conditions in VA ECMO. METHODS: In 13 pigs, extracorporeal flow was reduced from 4 to 1 L/min at baseline and increased afterload (pulmonary embolism and hypoxic vasoconstriction). Pressure and flow signals estimated right ventricular end-systolic elastance and pulmonary arterial elastance. Linear mixed-effect models estimated the association between conditions and elastance. RESULTS: At no extracorporeal flow, end-systolic elastance increased from 0.83 [0.66 to 1.00] mmHg/mL at baseline by 0.44 [0.29 to 0.59] mmHg/mL with pulmonary embolism and by 1.36 [1.21 to 1.51] mmHg/mL with hypoxic pulmonary vasoconstriction (p < 0.001). Pulmonary arterial elastance increased from 0.39 [0.30 to 0.49] mmHg/mL at baseline by 0.36 [0.27 to 0.44] mmHg/mL with pulmonary embolism and by 0.75 [0.67 to 0.84] mmHg/mL with hypoxic pulmonary vasoconstriction (p < 0.001). Coupling remained unchanged (2.1 [1.8 to 2.3] mmHg/mL at baseline; - 0.1 [- 0.3 to 0.1] mmHg/mL increase with pulmonary embolism; - 0.2 [- 0.4 to 0.0] mmHg/mL with hypoxic pulmonary vasoconstriction, p > 0.05). Extracorporeal flow did not change coupling (0.0 [- 0.0 to 0.1] per change of 1 L/min, p > 0.05). End-diastolic volume increased with decreasing extracorporeal flow (7.2 [6.6 to 7.8] ml change per 1 L/min, p < 0.001). CONCLUSIONS: The right ventricle dilates with increased preload and increases its contractility in response to afterload changes to maintain ventricular-arterial coupling during VA extracorporeal membrane oxygenation.

Substantial light woodland and open vegetation characterized the temperate forest biome before Homo sapiens.

The extent of vegetation openness in past European landscapes is widely debated. In particular, the temperate forest biome has traditionally been defined as dense, closed-canopy forest; however, some argue that large herbivores maintained greater openness or even wood-pasture conditions. Here, we address this question for the Last Interglacial period (129,000-116,000 years ago), before Homo sapiens-linked megafauna declines and anthropogenic landscape transformation. We applied the vegetation reconstruction method REVEALS to 96 Last Interglacial pollen records. We found that light woodland and open vegetation represented, on average, more than 50% cover during this period. The degree of openness was highly variable and only partially linked to climatic factors, indicating the importance of natural disturbance regimes. Our results show that the temperate forest biome was historically heterogeneous rather than uniformly dense, which is consistent with the dependency of much of contemporary European biodiversity on open vegetation and light woodland.

Interrater reliability of subacromial ultrasound measures in the hands of novice sonographers.

INTRODUCTION: Ultrasound measures of subacromial structures are reliable in the hands of experienced sonographers, but it remains unknown if inexperienced clinicians can achieve a satisfactory level of interrater reliability. The aim was to investigate if standardised subacromial ultrasound measures are reliable in the hands of novice sonographers. METHODS: Two novice sonographers performed standardised ultrasound measures on patients diagnosed with subacromial pain syndrome and asymptomatic shoulders. The measures were: supraspinatus tendon thickness (SUPRA), subacromial bursa thickness (SASD), acromio-humeral distance (AHD) and dynamic impingement (DI). Reliability and agreement were evaluated by intraclass correlation coefficient (ICC (2.1)), standard error of measurement, minimal detectable change, 95% limits of agreement, Bland-Altman plots and Cohen's unweighted κ. RESULTS: Twenty-eight patients were recruited (28 symptomatic and 20 asymptomatic shoulders). The ICC of SUPRA ranged from 0.73 to 0.77. The ICC of SASD ranged from 0.41 to 0.88 and AHD from 0.68 to 0.72. Cohen's κ of DI in symptomatic shoulders was 0.29. CONCLUSION: The interrater reliability of novice sonographers was found to be moderate to good when assessing SUPRA and AHD. For SASD and DI, the reliability ranged from poor to good. No significant differences in SUPRA and SASD thickness were found between symptomatic and asymptomatic shoulders. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Why human olfaction should not be modeled on theories and tasks of vision.

In this paper we analyze some key concepts and problems in olfaction and argue that many concepts borrowed from vision are not helpful in elucidating the functions of human olfaction. This is illustrated with several examples. Olfaction is rarely in the focus of human attention. Olfaction is, compared to vision, a 'hidden sense', but still guides many important behaviors by way of unattended unconscious olfactory perception and implicit memory. Not all olfactory processing, however, is of an unconscious nature. Flavors, and the pleasures gained from them, are most often consciously perceived. These are experiences mostly determined by olfaction, taste, touch and chemesthesis. Our analyses lead us to conclude that olfaction should not be modeled on vision, neither conceptually nor with respect to the problems solved by the two senses. A critical examination of the ecological and physical constraints of olfaction and the other senses should be given priority. Such analyses will further our understanding of which problems are solved by the different senses and how they collaborate to guide us through the world.

Interactions between extracorporeal support and the cardiopulmonary system.

This review describes the intricate physiological interactions involved in the application of extracorporeal therapy, with specific focus on cardiopulmonary relationships. Extracorporeal therapy significantly influences cardiovascular and pulmonary physiology, highlighting the necessity for clinicians to understand these interactions for improved patient care. Veno-arterial extracorporeal membrane oxygenation (veno-arterial ECMO) unloads the right ventricle and increases left ventricular (LV) afterload, potentially exacerbating LV failure and pulmonary edema. Veno-venous (VV) ECMO presents different challenges, where optimal device and ventilator settings remain unknown. Influences on right heart function and native gas exchange as well as end-expiratory lung volumes are important concepts that should be incorporated into daily practice. Future studies should not be limited to large clinical trials focused on mortality but rather address physiological questions to advance the understanding of extracorporeal therapies. This includes exploring optimal device and ventilator settings in VV ECMO, standardizing cardiopulmonary function monitoring strategies, and developing better strategies for device management throughout their use. In this regard, small human or animal studies and computational physiological modeling may contribute valuable insights into optimizing the management of extracorporeal therapies.

Cardiopulmonary interactions-which monitoring tools to use?

Heart-lung interactions occur due to the mechanical influence of intrathoracic pressure and lung volume changes on cardiac and circulatory function. These interactions manifest as respiratory fluctuations in venous, pulmonary, and arterial pressures, potentially affecting stroke volume. In the context of functional hemodynamic monitoring, pulse or stroke volume variation (pulse pressure variation or stroke volume variability) are commonly employed to assess volume or preload responsiveness. However, correct interpretation of these parameters requires a comprehensive understanding of the physiological factors that determine pulse pressure and stroke volume. These factors include pleural pressure, venous return, pulmonary vessel function, lung mechanics, gas exchange, and specific cardiac factors. A comprehensive knowledge of heart-lung physiology is vital to avoid clinical misjudgments, particularly in cases of right ventricular (RV) failure or diastolic dysfunction. Therefore, when selecting monitoring devices or technologies, these factors must be considered. Invasive arterial pressure measurements of variations in breath-to-breath pressure swings are commonly used to monitor heart-lung interactions. Echocardiography or pulmonary artery catheters are valuable tools for differentiating preload responsiveness from right ventricular failure, while changes in diastolic function should be assessed alongside alterations in airway or pleural pressure, which can be approximated by esophageal pressure. In complex clinical scenarios like ARDS, combined forms of shock or right heart failure, additional information on gas exchange and pulmonary mechanics aids in the interpretation of heart-lung interactions. This review aims to describe monitoring techniques that provide clinicians with an integrative understanding of a patient's condition, enabling accurate assessment and patient care.

Effects of COVID-19 on Sense of Smell: Human Factors/Ergonomics Considerations.

OBJECTIVE: We review the effects of COVID-19 on the human sense of smell (olfaction) and discuss implications for human-system interactions. We emphasize how critical smell is and how the widespread loss of smell due to COVID-19 will impact human-system interaction. BACKGROUND: COVID-19 reduces the sense of smell in people who contract the disease. Thus far, olfaction has received relatively little attention from human factors/ergonomics professionals. While smell is not a primary means of human-system communication, humans rely on smell in many important ways related to both quality of life and safety. METHOD: We briefly review and synthesize the rapidly expanding literature through September 2020 on the topic of smell loss caused by COVID-19. We interpret findings in terms of their relevance to human factors/ergonomics researchers and practitioners. RESULTS: Since March 2020 dozens of articles have been published that report smell loss in COVID-19 patients. The prevalence and duration of COVID-19-related smell loss is still under investigation, but the available data suggest that it may leave many people with long-term deficits and distortions in sense of smell. CONCLUSION: We suggest that the human factors/ergonomics community could become more aware of the importance of the sense of smell and focus on accommodating the increasing number of people with reduced olfactory performance. APPLICATION: We present examples of how olfaction can augment human-system communication and how human factors/ergonomics professionals might accommodate people with olfactory dysfunction. While seemingly at odds, both of these goals can be achieved.

Experimental validation of a mean systemic pressure analog against zero-flow measurements in porcine VA-ECMO.

The mean systemic pressure analog (Pmsa), calculated from running hemodynamic data, estimates mean systemic filling pressure (MSFP). This post hoc study used data from a porcine veno-arterial extracorporeal membrane oxygenation (ECMO) model [n = 9; Sus scrofa domesticus; ES breed (Schweizer Edelschwein)] with eight experimental conditions; Euvolemia [a volume state where ECMO flow produced normal mixed venous saturation (SVO2) without vascular collapse]; three levels of increasing norepinephrine infusion (Vasoconstriction 1-3); status after stopping norepinephrine (Post Vasoconstriction); and three steps of volume expansion (10 mL/kg crystalloid bolus) (Volume Expansion 1-3). In each condition, Pmsa and a "reduced-pump-speed-Pmsa" (Pmsared) were calculated from baseline and briefly reduced pump speeds, respectively. We calculated agreement for absolute values (per condition) and changes (between consecutive conditions) of Pmsa and Pmsared, against MSFP at zero ECMO flow. Euvolemia venous return driving pressure was 5.1 ± 2.0 mmHg. Bland-Altman analysis for Pmsa vs. MSFP (all conditions; 72 data pairs) showed bias (confidence interval) 0.5 (0.1-0.9) mmHg; limits of agreement (LoA) -2.7 to 3.8 mmHg. Bias for ΔPmsa vs. ΔMSFP (63 data pairs): 0.2 (-0.2 to 0.6) mmHg, LoA -3.2 to 3.6 mmHg. Bias for Pmsared vs. MSFP (72 data pairs): 0.0 (-0.3 to -0.3) mmHg; LoA -2.3 to 2.4 mmHg. Bias for ΔPmsared vs. ΔMSFP (63 data pairs) was 0.2 (-0.1 to 0.4) mmHg; LoA -1.8 to 2.1 mmHg. In conclusion, during veno-arterial ECMO, under clinically relevant levels of vasoconstriction and volume expansion, Pmsa accurately estimated absolute and changing values of MSFP, with low between-method precision. The within-method precision of Pmsa was excellent, with a least significant change of 0.15 mmHg.NEW & NOTEWORTHY This is the first study ever to validate the mean systemic pressure analog (Pmsa) against the reference mean systemic filling pressure (MSFP) determined at full arterio-venous pressure equilibrium. Using a porcine ECMO model with clinically relevant levels of vasoconstriction and volume expansion, we showed that Pmsa accurately estimated absolute and changing values of MSFP, with a poor between-method precision. The within-method precision of Pmsa was excellent.

Late Quaternary dynamics of Arctic biota from ancient environmental genomics.

During the last glacial-interglacial cycle, Arctic biotas experienced substantial climatic changes, yet the nature, extent and rate of their responses are not fully understood1-8. Here we report a large-scale environmental DNA metagenomic study of ancient plant and mammal communities, analysing 535 permafrost and lake sediment samples from across the Arctic spanning the past 50,000 years. Furthermore, we present 1,541 contemporary plant genome assemblies that were generated as reference sequences. Our study provides several insights into the long-term dynamics of the Arctic biota at the circumpolar and regional scales. Our key findings include: (1) a relatively homogeneous steppe-tundra flora dominated the Arctic during the Last Glacial Maximum, followed by regional divergence of vegetation during the Holocene epoch; (2) certain grazing animals consistently co-occurred in space and time; (3) humans appear to have been a minor factor in driving animal distributions; (4) higher effective precipitation, as well as an increase in the proportion of wetland plants, show negative effects on animal diversity; (5) the persistence of the steppe-tundra vegetation in northern Siberia enabled the late survival of several now-extinct megafauna species, including the woolly mammoth until 3.9 ± 0.2 thousand years ago (ka) and the woolly rhinoceros until 9.8 ± 0.2 ka; and (6) phylogenetic analysis of mammoth environmental DNA reveals a previously unsampled mitochondrial lineage. Our findings highlight the power of ancient environmental metagenomics analyses to advance understanding of population histories and long-term ecological dynamics.

Is Novelty Detection Important in Long-Term Odor Memory?

Memory for odors is believed to be longer-lasting than memory for visual stimuli, as is evidenced by flat forgetting curves. However, performance on memory tasks is typically weaker in olfaction than vision. Studies of odor memory that use forced-choice methods confound responses that are a result of a trace memory and responses that can be obtained through process of elimination. Moreover, odor memory is typically measured with common stimuli, which are more familiar and responses may be confounded by verbal memory, and measure memory in intentional learning conditions, which are ecologically questionable. Here we demonstrate the value of using tests of memory in which hit rate and correct rejection rate are evaluated separately (i.e., not using forced-choice methods) and uncommon stimuli are used. This study compared memory for common and uncommon odors and pictures that were learned either intentionally (Exp. 1) or incidentally (Exp. 2) and tested with either a forced-choice or a one-stimulus-at-a-time ("monadic") recognition task after delays of 15 min, 48 h or 1 week. As expected, memory declined with delay in most conditions, but depended upon the particular measure of memory and was better for pictures than odors and for common than uncommon stimuli. For common odors, hit rates decreased with delay but correct rejection rates remained constant with delay. For common pictures, we found the opposite result, constant hit rates and decreased correct rejection rates. Our results support the 'misfit theory of conscious olfactory perception', which highlights the importance of the detection of novelty in olfactory memory and suggests that olfactory memory should be studied using more ecologically valid methods.