A cross-disciplinary approach to learning medical physiology and behavioral skills involving drama students performing as simulated patients.

The early years of physiology education in medical curricula provide unique challenges. As well as inculcating concepts that are seen as difficult, modern curricula require that students learn in context in case-based learning courses. Additionally, regulating bodies stress that the soft skills of compassion, communication, and empathy are embedded throughout curricula. This has driven work in our organization involving drama and final-year medicine students during which they collaborate in realistic simulations of doctor/patient interactions. We adapted this transdisciplinary approach to second-year physiology tutorials. This emphasized the holistic importance of physiology to patient care, while also embedding "human factors" skills from the very earliest stages of the curriculum. After preparing by attending acting classes based on aspects of Konstantin Stanislavski's "System," the authors supervised tutorials in which drama students participated in a "physiology of hypofertility" session for second-year medical students, playing a 34-year-old woman with premature menopause (or their partner). Opinion (from all students) was evaluated by Likert questionnaires (which included open questions). A focus group of drama students was also interviewed, and the conversation was recorded for thematic analysis. Positive Likert scores were recorded for the authenticity of the tutorials, skills development, fostering empathy, and motivating students to improve. All participants evaluated the tutorial as highly enjoyable. These scores are reflected in positive open commentary on the questionnaires and in the focus group interviews. The results suggest that even basic science tutorials give opportunities for interdisciplinary study and enhancement of behavioral skills while gaining enthusiastic student acceptance.NEW & NOTEWORTHY This work details how physiology tutorials for early years medical students are transformed by taking the clinical case off the two-dimensional page and instead having the case scenario acted by drama students. This adds context and authenticity. The benefits are twofold: emphasizing the importance of physiology to the budding clinician and embedding empathy and compassion from the earliest points in a clinician's career.

Ultrasound imaging in teaching cardiovascular physiology: disruption and challenge to foster learning.

This work extends previously described applications of ultrasound technology in illustrating cardiovascular phenomena to investigation of learning effectiveness. To this end, learning in ultrasound-enhanced classes was assessed by quantifying the improvement in single best answer (SBA) exams conducted before and after an ultrasound practical class. This improvement was then compared to that seen in the same SBA exams conducted in matched groups that undertook similar classes conducted without ultrasound equipment. The SBA exams were designed to include questions that directly related to the phenomena being investigated in the practical classes as well as other "filler" questions to disguise the intent of the exam and ensure that standards of physiology knowledge were similar between the two groups. Any small statistically significant gains in performance observed between the two groups were confounded by differences in baseline (pretest) performance between the groups. These results contradict our previous work, which showed that self-reported measures of learning increased after ultrasound classes. It may be optimistic to expect improvements in deep learning and test performance immediately after even the most effective educational intervention. Direct measurement of the phenomena that bring about deep, long-term learning in classes remains problematic. Notwithstanding this, there is much evidence for the value of enhancing physiology learning by providing varying contexts in the physical, semantic, and cognitive domains. Ultrasound technology is a cheap and effective means of providing such context in physiology practical classes.NEW & NOTEWORTHY This work compares learning in cardiovascular physiology classes enhanced by using cheap ultrasound equipment with learning in comparable control classes without ultrasound. Performance improvement in single best answer tests between pre- and postclass tests were compared for the ultrasound and control classes, with little difference shown between the two classes. We question whether it is appropriate to measure deep learning after 2-h classes or whether other, phenomenological, qualitative measures of educational effectiveness would be better.

Rotationally-Resolved Two-Dimensional Infrared Spectroscopy of CO2(g): Rotational Wavepackets and Angular Momentum Transfer.

Angular momentum transfer and wavepacket dynamics of CO2(g) were measured on the picosecond time scale using polarization-resolved two-dimensional infrared (2D-IR) spectroscopy. The dynamics of rotational levels up to Jmax ≈ 50 are observed simultaneously at room temperature. Rotational wavepackets launched by the pump pulses cause oscillations in the intensity of individual peaks and beating patterns in the 2D-IR spectra. The structure of the rotationally resolved 2D-IR spectrum is explained using nonlinear response function theory. Spectral diffusion of the rotationally resolved 2D-IR peaks reveals information about angular momentum transfer. We demonstrate the ability to directly measure inelastic angular momentum dynamics simultaneously across the ∼50 thermally excited rotational levels over several hundred picoseconds.

pH Jumps in a Protic Ionic Liquid Proceed by Vehicular Proton Transport.

The dynamics of excess protons in the protic ionic liquid (PIL) ethylammonium formate (EAF) have been investigated from femtoseconds to microseconds using visible pump mid-infrared probe spectroscopy. The pH jump following the visible photoexcitation of a photoacid (8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt, HPTS) results in proton transfer to the formate of the EAF. The proton transfer predominantly (∼70%) occurs over picoseconds through a preformed hydrogen-bonded tight complex between HPTS and EAF. We investigate the longer-range and longer-time-scale proton-transport processes in the PIL by obtaining the ground-state conjugate base (RO-) dynamics from the congested transient-infrared spectra. The spectral kinetics indicate that the protons diffuse only a few solvent shells from the parent photoacid before recombining with RO-. A kinetic isotope effect of nearly unity (kH/kD ≈ 1) suggests vehicular transfer and the transport of excess protons in this PIL. Our findings provide comprehensive insight into the complete photoprotolytic cycle of excess protons in a PIL.

CH Mode Mixing Determines the Band Shape of the Carboxylate Symmetric Stretch in Apo-EDTA, Ca2+-EDTA, and Mg2+-EDTA.

The infrared spectra of EDTA complexed with Ca2+ and Mg2+ contain, to date, unidentified vibrational bands. This study assigns the peaks in the linear and two-dimensional infrared spectra of EDTA, with and without either Ca2+ or Mg2+ ions. Two-dimensional infrared spectroscopy and DFT calculations reveal that, in both the presence and absence of ions, the carboxylate symmetric stretch and the terminal CH bending vibrations mix. We introduce a method to calculate participation coefficients that quantify the contribution of the carboxylate symmetric stretch, CH wag, CH twist, and CH scissor in the 1400-1550 cm-1 region. With the help of participation coefficients, we assign the 1400-1430 cm-1 region to the carboxylate symmetric stretch, which can mix with CH modes. We assign the 1000-1380 cm-1 region to CH twist modes, the 1380-1430 cm-1 region to wag modes, and the 1420-1650 cm-1 region to scissor modes. The difference in binding geometry between the carboxylate-Ca2+ and carboxylate-Mg2+ complex manifests as new diagonal and cross-peaks between the mixed modes in the two complexes. The small Mg2+ ion binds EDTA tighter than the Ca2+ ion, which causes a redshift of the COO symmetric stretches of the sagittal carboxylates. Energy decomposition analysis further characterizes the importance of electrostatics and deformation energy in the bound complexes.

An ultrafast vibrational study of dynamical heterogeneity in the protic ionic liquid ethyl-ammonium nitrate. I. Room temperature dynamics.

Using ultrafast two-dimensional infrared spectroscopy (2D-IR), a vibrational probe (thiocyanate, SCN-) was used to investigate the hydrogen bonding network of the protic ionic liquid ethyl-ammonium nitrate (EAN) in comparison to H2O. The 2D-IR experiments were performed in both parallel (⟨ZZZZ⟩) and perpendicular (⟨ZZXX⟩) polarizations at room temperature. In EAN, the non-Gaussian lineshape in the FTIR spectrum of SCN- suggests two sub-ensembles. Vibrational relaxation rates extracted from the 2D-IR spectra provide evidence of the dynamical differences between the two sub-ensembles. We support the interpretation of two sub-ensembles with response function simulations of two overlapping bands with different vibrational relaxation rates and, otherwise, similar dynamics. The measured rates for spectral diffusion depend on polarization, indicating reorientation-induced spectral diffusion (RISD). A model of restricted molecular rotation (wobbling in a cone) fully describes the observed spectral diffusion in EAN. In H2O, both RISD and structural spectral diffusion contribute with similar timescales. This complete characterization of the dynamics at room temperature provides the basis for the temperature-dependent measurements in Paper II of this series.

Intramolecular Vibrational Energy Relaxation of CO2 in Cross-Linked Poly(ethylene glycol) Diacrylate-Based Ion Gels.

Ultrafast two-dimensional infrared spectroscopy (2D-IR) and Fourier transform infrared spectroscopy (FTIR) were used to measure carbon dioxide (CO2) in 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([emim][Tf2N]), cross-linked low-molecular-weight poly(ethylene glycol) diacrylate (PEGDA), and an ion gel composed of a 50 vol % blend of the two. The center frequency of the antisymmetric stretch, ν3, of CO2 shifts monotonically to lower wavenumbers with increasing polymer content, with the largest line width in the ion gel (6 cm-1). Increasing polymer content slows both spectral diffusion and vibrational energy relaxation (VER) rates. An unexpected excited-state absorbance peak appears in the 2D-IR of cross-linked PEGDA due to VER from the antisymmetric stretch into the bending mode, ν2. Thirty-two response functions are necessary to describe the observed features in the 2D-IR spectra. Nonlinear least-squares fitting extracts both spectral diffusion and VER rates. In the ion gel, CO2 exhibits spectral diffusion dynamics that lie between that of the pure compounds. The kinetics of VER reflect both fast excitation and de-excitation of the bending mode, similar to the ionic liquid (IL), and slow overall vibrational population relaxation, similar to the cross-linked polymer. The IL-like and polymer-like dynamics suggest that the CO2 resides at the interface of the two components in the ion gel.

Vibrational Spectroscopic Map, Vibrational Spectroscopy, and Intermolecular Interaction.

Vibrational spectroscopy is an essential tool in chemical analyses, biological assays, and studies of functional materials. Over the past decade, various coherent nonlinear vibrational spectroscopic techniques have been developed and enabled researchers to study time-correlations of the fluctuating frequencies that are directly related to solute-solvent dynamics, dynamical changes in molecular conformations and local electrostatic environments, chemical and biochemical reactions, protein structural dynamics and functions, characteristic processes of functional materials, and so on. In order to gain incisive and quantitative information on the local electrostatic environment, molecular conformation, protein structure and interprotein contacts, ligand binding kinetics, and electric and optical properties of functional materials, a variety of vibrational probes have been developed and site-specifically incorporated into molecular, biological, and material systems for time-resolved vibrational spectroscopic investigation. However, still, an all-encompassing theory that describes the vibrational solvatochromism, electrochromism, and dynamic fluctuation of vibrational frequencies has not been completely established mainly due to the intrinsic complexity of intermolecular interactions in condensed phases. In particular, the amount of data obtained from the linear and nonlinear vibrational spectroscopic experiments has been rapidly increasing, but the lack of a quantitative method to interpret these measurements has been one major obstacle in broadening the applications of these methods. Among various theoretical models, one of the most successful approaches is a semiempirical model generally referred to as the vibrational spectroscopic map that is based on a rigorous theory of intermolecular interactions. Recently, genetic algorithm, neural network, and machine learning approaches have been applied to the development of vibrational solvatochromism theory. In this review, we provide comprehensive descriptions of the theoretical foundation and various examples showing its extraordinary successes in the interpretations of experimental observations. In addition, a brief introduction to a newly created repository Web site (http://frequencymap.org) for vibrational spectroscopic maps is presented. We anticipate that a combination of the vibrational frequency map approach and state-of-the-art multidimensional vibrational spectroscopy will be one of the most fruitful ways to study the structure and dynamics of chemical, biological, and functional molecular systems in the future.

Using two-dimensional ultrasound imaging to examine venous pressure.

Ultrasound imaging is being used increasingly to aid in the teaching of human physiology and anatomy. Here we describe how its use can be integrated into the teaching of concepts surrounding venous circulation, specifically 1) venous valves and the muscle pump, 2) the effects of hydrostatic pressure on venous pressure, and 3) central venous pressure. The imaging procedures described are relatively simple but add a dimension that helps deliver the teaching points clearly and is enjoyable for students. They also aid in the link of basic physiology to clinical aspects of venous circulatory physiology.

Understanding basic vein physiology and venous blood pressure through simple physical assessments.

An understanding of the complexity of the cardiovascular system is incomplete without a knowledge of the venous system. It is important for students to understand that, in a closed system, like the circulatory system, changes to the venous side of the circulation have a knock-on effect on heart function and the arterial system and vice versa. Veins are capacitance vessels feeding blood to the right side of the heart. Changes in venous compliance have large effects on the volume of blood entering the heart and hence cardiac output by the Frank-Starling Law. In healthy steady-state conditions, venous return has to equal cardiac output, i.e., the heart cannot pump more blood than is delivered to it. A sound understanding of the venous system is essential in understanding how changes in cardiac output occur with changes in right atrial pressure or central venous pressure, and the effect these changes have on arterial blood pressure regulation. The aim of this paper is to detail simple hands-on physiological assessments that can be easily undertaken in the practical laboratory setting and that illustrate some key functions of veins. Specifically, we illustrate that venous valves prevent the backflow of blood, that venous blood pressure increases from the heart to the feet, that the skeletal muscle pump facilitates venous return, and we investigate the physiological and clinical significance of central venous pressure and how it may be assessed.

Modeling Carbon Dioxide Vibrational Frequencies in Ionic Liquids: III. Dynamics and Spectroscopy.

In recent years, interest in carbon capture and sequestration has led to numerous investigations of the ability of ionic liquids to act as recyclable CO2-sorbent materials. Herein, we investigate the structure and dynamics of a model physisorbing ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate ([C4C1Im][PF6]), from the perspective of CO2 using two-dimensional (2D) IR spectroscopy and molecular dynamics simulations. A direct comparison of experimentally measured and calculated 2D IR line shapes confirms the validity of the simulations and spectroscopic calculations. Taken together, the simulations and experiments reveal new insights into the interactions of a CO2 solute with the surrounding ionic liquid and how these interactions manifest in the 2D IR spectra. In particular, higher CO2 asymmetric stretch vibrational frequencies are associated with softer, less populated solvent cages and lower frequencies are associated with tighter, more highly populated solvent cages. The CO2 interacts most strongly with the anions, and these interactions persist for more than 1 ns. The second strongest interactions are with the imidazolium cation ring that last 100 ps, and the weakest interactions are with the cation butyl tail that persist for 10 ps. The principal contributors to spectral diffusion of the CO2 asymmetric stretch vibrational frequency due to the dynamical evolution of the solvent are through Lennard-Jones interactions at short times and electrostatics at long times.

Enthalpic Driving Force for the Selective Absorption of CO2 by an Ionic Liquid.

Molecular dynamics (MD) simulations validated against two-dimensional infrared (2D-IR) measurements of CO2 in an imidazolium-based ionic liquid have revealed new insights into the mechanism of CO2 solvation. The first solvation shell around CO2 has a distinctly quadrupolar structure, with strong negative charge density around the CO2 carbon atom and positive charge density near the CO2 oxygen atoms. When CO2 is modeled without atomic charges (thus removing its strong quadrupole moment), its solvation shell weakens and changes significantly into a structure that is similar to that of N2 in the same liquid. The solvation shell of CO2 evolves more quickly when its quadrupole is removed, and we find evidence that solvent cage dynamics is measured by 2D-IR spectroscopy. We also find that the solvent cage evolution of N2 is similar to that of CO2 with no atomic charges, implying that the weaker quadrupole of N2 is responsible for its higher diffusion and lower absorption in ionic liquids.

Ultrafast dynamics of ionic liquids in colloidal dispersion.

Ionic liquid (IL)-surfactant complexes have significance both in applications and fundamental research, but their underlying dynamics are not well understood. We apply polarization-controlled two-dimensional infrared spectroscopy (2D-IR) to study the dynamics of [BMIM][SCN]/surfactant/solvent model systems. We examine the effect of the choice of surfactants and solvent, and the IL-to-surfactant ratio (W-value), with a detailed analysis of the orientation and structural dynamics of each system. Different surfactants create very different environments for the entrapped ILs, ranging from a semi-static micro-environment to a fluxional environment that evolves even faster than the bulk IL. The oil-phase also clearly affects the microscopic dynamics. The anisotropy decay for entrapped ILs completes within 10 ps, which is similar to free thiocyanate ion in water, while a significant reorientation-induced spectral diffusion (RISD) effect is observed. The entrapped ionic liquid are highly dynamic for all W-values, and no core-shell structure is observed. We hypothesize that, instead of an ionic liquid-reverse micelle (IL-RM), the microscopic structure of this system is small colloidal dispersions or pairs of IL and surfactants. A detailed analysis of the polarization-controlled 2D-IR spectra of AOT system reveals a potential ion-exchange mechanism.

Temperature and chain length dependence of ultrafast vibrational dynamics of thiocyanate in alkylimidazolium ionic liquids: A random walk on a rugged energy landscape.

Ultrafast two-dimensional infrared spectroscopy of a thiocyanate vibrational probe (SCN-) was used to investigate local dynamics in alkylimidazolium bis-[trifluoromethylsulfonyl]imide ionic liquids ([Imn,1][Tf2N], n = 2, 4, 6) at temperatures from 5 to 80 °C. The rate of frequency fluctuations reported by SCN- increases with increasing temperature and decreasing alkyl chain length. Temperature-dependent correlation times scale proportionally to temperature-dependent bulk viscosities of each ionic liquid studied. A multimode Brownian oscillator model demonstrates that very low frequency (<10 cm-1) modes primarily drive the observed spectral diffusion and that these modes broaden and blue shift on average with increasing temperature. An Arrhenius analysis shows activation barriers for local motions around the probe between 5.5 and 6.5 kcal/mol that are very similar to those for translational diffusion of ions. [Im6,1][Tf2N] shows an unexpected decrease in activation energy compared to [Im4,1][Tf2N] that may be related to mesoscopically ordered polar and nonpolar domains. A model of dynamics on a rugged potential energy landscape provides a unifying description of the observed Arrhenius behavior and the Brownian oscillator model of the low frequency modes.

Reorientation-induced spectral diffusion of non-isotropic orientation distributions.

When reorientation of a vibrational chromophore is faster than the relaxation of its local environment, the frequency fluctuation correlation function (FFCF) measured by two-dimensional infrared spectroscopy (2D-IR) spectroscopy is an interplay of scalar structural spectral diffusion and vectorial reorientation-induced spectral diffusion (RISD). Theory has been established to calculate the RISD component of different polarization configurations with the assumption that the molecule orients randomly in a local electric field. We show here that in the [BMIM][SCN]/AOT/chlorobenzene system, where the local electric field is strong, this assumption is incapable of reproducing the experimental results. We modify the current theory by assuming a Boltzmann distribution of transition dipoles of the chromophores in a local electric field and use a Markov chain model to calculate the RISD component of 2D-IR with different polarization configurations. The result reproduces key features of the experiment and suggests a potential ion-exchange in the [BMIM][SCN]/AOT/chlorobenzene system.

Modeling Carbon Dioxide Vibrational Frequencies in Ionic Liquids: I. Ab Initio Calculations.

This work elucidates the molecular binding mechanism of CO2 in [C4C1IM][PF6] ionic liquid (IL) and its interplay with the CO2 asymmetric stretch frequency ν3, and establishes computational protocols for the reliable construction of spectroscopic maps for simulating ultrafast 2D-IR data of CO2 solvated in ILs. While charge transfer drives the static frequency shift between different ionic liquids ( J. Chem. Phys. 2015 , 142 , 212425 ), we find here that electrostatic and Pauli repulsion effects dominate the dynamical frequency shift between different geometries sampled from the finite-temperature dynamics within a single ionic liquid. This finding is also surprising because dispersion interactions dominate the CO2-IL interaction energies, but are comparably constant across different geometries. An important practical consequence of this finding is that density functional theory is expected to be sufficiently accurate for constructing potential energy surfaces for CO2 in [C4C1IM][PF6], as needed for accurate anharmonic calculations to construct a reliable spectroscopic map. Similarly, we established appropriate computational and chemical models for treating the extended solvent environment. We found that a QM/MM treatment including at least 2 cation-ion pairs at the QM level and at least 32 pairs at the MM level is necessary to converge vibrational frequencies to within 1 cm-1. Using these insights, this work identifies a computational protocol as well as a chemical model necessary to construct accurate spectroscopic maps from first principles.

Modeling Carbon Dioxide Vibrational Frequencies in Ionic Liquids: II. Spectroscopic Map.

The primary challenge for connecting molecular dynamics (MD) simulations to linear and two-dimensional infrared measurements is the calculation of the vibrational frequency for the chromophore of interest. Computing the vibrational frequency at each time step of the simulation with a quantum mechanical method like density functional theory (DFT) is generally prohibitively expensive. One approach to circumnavigate this problem is the use of spectroscopic maps. Spectroscopic maps are empirical relationships that correlate the frequency of interest to properties of the surrounding solvent that are readily accessible in the MD simulation. Here, we develop a spectroscopic map for the asymmetric stretch of CO2 in the 1-butyl-3-methylimidazolium hexafluorophosphate ([C4C1im][PF6]) ionic liquid (IL). DFT is used to compute the vibrational frequency of 500 statistically independent CO2-[C4C1im][PF6] clusters extracted from an MD simulation. When the map was tested on 500 different CO2-[C4C1im][PF6] clusters, the correlation coefficient between the benchmark frequencies and the predicted frequencies was R = 0.94, and the root-mean-square error was 2.7 cm-1. The calculated distribution of frequencies also agrees well with experiment. The spectroscopic map required information about the CO2 angle, the electrostatics of the surrounding solvent, and the Lennard-Jones interaction between the CO2 and the IL. The contribution of each term in the map was investigated using symmetry-adapted perturbation theory calculations.

Ultrasound imaging in teaching cardiac physiology.

This laboratory session provides hands-on experience for students to visualize the beating human heart with ultrasound imaging. Simple views are obtained from which students can directly measure important cardiac dimensions in systole and diastole. This allows students to derive, from first principles, important measures of cardiac function, such as stroke volume, ejection fraction, and cardiac output. By repeating the measurements from a subject after a brief exercise period, an increase in stroke volume and ejection fraction are easily demonstrable, potentially with or without an increase in left ventricular end-diastolic volume (which indicates preload). Thus, factors that affect cardiac performance can readily be discussed. This activity may be performed as a practical demonstration and visualized using an overhead projector or networked computers, concentrating on using the ultrasound images to teach basic physiological principles. This has proved to be highly popular with students, who reported a significant improvement in their understanding of Frank-Starling's law of the heart with ultrasound imaging.