Real-time speech MRI datasets with corresponding articulator ground-truth segmentations.

The use of real-time magnetic resonance imaging (rt-MRI) of speech is increasing in clinical practice and speech science research. Analysis of such images often requires segmentation of articulators and the vocal tract, and the community is turning to deep-learning-based methods to perform this segmentation. While there are publicly available rt-MRI datasets of speech, these do not include ground-truth (GT) segmentations, a key requirement for the development of deep-learning-based segmentation methods. To begin to address this barrier, this work presents rt-MRI speech datasets of five healthy adult volunteers with corresponding GT segmentations and velopharyngeal closure patterns. The images were acquired using standard clinical MRI scanners, coils and sequences to facilitate acquisition of similar images in other centres. The datasets include manually created GT segmentations of six anatomical features including the tongue, soft palate and vocal tract. In addition, this work makes code and instructions to implement a current state-of-the-art deep-learning-based method to segment rt-MRI speech datasets publicly available, thus providing the community and others with a starting point for developing such methods.

Clinical Ethics and Professional Integrity: A Comment on the ASBH Code.

The Code of Ethics and Professional Responsibilities for Healthcare Ethics Consultants instructs clinical ethics consultants to preserve their professional integrity by "not engaging in activities that involve giving an ethical justification or stamp of approval to practices they believe are inconsistent with agreed-upon standards" (ASBH, 2014, p. 2). This instruction reflects a larger model of how to address value uncertainty and moral conflict in healthcare, and it brings up some intriguing and as yet unanswered questions-ones that the drafters of the Code, and the profession more broadly, should seek to address in upcoming revisions. The objective of this article is to raise these questions as a way of urging greater clarification of the Code's overall approach to professional integrity, its meaning, and implications.

Effects of spatial and temporal resolution on cardiovascular magnetic resonance feature tracking measurements using a simple realistic numerical phantom.

OBJECTIVES: To develop a single-slice numerical phantom with known myocardial motion, at several temporal and in-plane spatial resolutions, for testing and comparison of Cardiovascular Magnetic Resonance (CMR) feature tracking (FT) software. METHODS: The phantom was developed based on CMR acquisitions of one volunteer (acquired cine, tagging cine, T1 map, T2 map, proton density weighted image). The numerical MRI simulator JEMRIS was used, and the phantom was generated at several in-plane spatial resolutions (1.4 × 1.4 mm2 to 3.0 × 3.0 mm2) and temporal resolutions (20 to 40 cardiac phases). Two feature tracking software packages were tested: Medical Image Tracking Toolbox (MITT) and two versions of cvi42 (v5.3.8 and v5.13.7). The effect of resolution on strain results was investigated with reference to ground-truth radial and circumferential strain. RESULTS: Peak radial strain was consistently undermeasured more for cvi42 v5.13.7 than for v5.3.8. Increased pixel size produced a trend of increased difference from ground-truth peak strain, with the largest changes for cvi42 obtained using v5.13.7 between 1.4 × 1.4 mm2 and 3.0 × 3.0 mm2, at 9.17 percentage points (radial) and 8.42 percentage points (circumferential). CONCLUSIONS: The results corroborate the presence of intervendor differences in feature tracking results and show the magnitude of strain differences between software versions. ADVANCES IN KNOWLEDGE: This study shows how temporal and in-plane spatial resolution can affect feature tracking with reference to the ground-truth strain of a numerical phantom. Results reaffirm the need for numerical phantom development for the validation and testing of FT software.

Increasing hypoxia progressively slows early embryonic development in an oviparous reptile, the green turtle, Chelonia mydas.

Green turtle (Chelonia mydas) embryos are in an arrested state of development when the eggs are laid, but in the presence of oxygen, arrest is broken and development resumes within 12-16 h. However, the precise oxygen level at which embryos break arrest and continue development is not known. To better understand the impact of oxygen concentration on breaking of arrest and early embryonic development, we incubated freshly laid eggs of the green sea turtle for three days at each of six different oxygen concentrations (less than or equal to 1%, 3%, 5%, 7%, 9% and 21%) and monitored the appearance and growth of white spots on the shell, indicative of embryonic development. As reported previously, white spots did not develop on eggs incubated in anoxia (less than or equal to 1% oxygen). For all other treatments, mean time to white spot detection and white spot growth rate varied inversely with oxygen concentration. In nearly all cases the difference between eggs at different oxygen levels was statistically significant (p ≤ 0.05). This suggests that sea turtle embryonic development may respond to oxygen in a dose-dependent manner. Our results indicate that the development of green turtle embryos may be slowed if they are exposed to the most hypoxic conditions reported in mature natural nests.

Consensus, clinical decision making, and unsettled cases.

The model of clinical ethics consultation (CEC) defended in the ASBH Core Competencies report has gained significant traction among scholars and healthcare providers. On this model, the aim of CEC is to facilitate deliberative reflection and thereby resolve conflicts and clarify value uncertainty by invoking and pursuing a process of consensus building. It is central to the model that the facilitated consensus falls within a range of allowable options, defined by societal values: prevailing legal requirements, widely endorsed organizational policies, and professional standards of practice and codes of conduct. Moreover, the model stipulates that ethics consultants must refrain from giving substantive recommendations regarding how parties to a moral disagreement in the clinic should evaluate their options. We argue that this model of CEC is incomplete, because it wrongly assumes that what counts as the proper set of allowable options among which the parties are to deliberate will itself always be clearly discernible. We illustrate this problem with a recent case on which one of us consulted-a neonate born with trisomy 18 (T18). We try to show that law, policy, and standards of practice reveal no clear answer to the question posed by the case: namely, whether forgoing gastrostomy tube feedings for a baby with T18 is allowable. We suggest there may be other kinds of cases in which it may simply be unsettled whether a given choice falls within the set of allowable options within which consensus is to be facilitated. What should an ethicist do when confronting such unsettled cases? We agree with the facilitation model that an ethicist should remain neutral among the allowable options, when it is clear what the allowable options are. But, in unsettled cases, the role of a consultant should be expanded to include a process of moral inquiry into what the allowable options should be. We end by raising the issue of whether this means an ethicist should share his or her own conclusions or views about the allowability of a given clinical option.

The role of the clinical ethics consultant in "unsettled" cases.

In this article I take up a central question posed by the article jointly authored with Bill Winslade in this issue of JCE: What should be the role of clinical ethics consultants (CECs) in (what we call) an unsettled case: that is, a situation in which the range of allowable choices, among which the parties to a bioethical disagreement must select, cannot be clearly or completely specified? I argue here that CECs should, in such cases, guide the parties by presenting their own reasoned conclusions about what the scope of allowable choices should be taken to include. Since this position challenges the received view that CECs must not express their own moral positions or conclusions in their role as ethicists, I try to defend my view of the CEC's role in unsettled cases against several objections.

Ultrafast spectroscopy of the solvent dependence of electron transfer in a perylenebisimide dimer.

We investigate the photoinduced intramolecular electron-transfer (IET) behavior of a perylenebisimide dimer in a variety of solvents using femtosecond transient absorption spectroscopy. Overlapping photoinduced absorptions and stimulated emission give rise to complicated traces, but they are well fit with a simple kinetic model. IET rates were found to depend heavily on solvent dielectric constant. Good quantitative agreement with rates derived from fluorescence quantum yield and time-resolved fluorescence measurements was found for forward electron transfer and charge recombination rates.

Molecular switch based on a biologically important redox reaction.

Building on our earlier report of a single-molecule probe, we show how biologically important redox centers, nicotinamide and quinone, incorporated into a fluorophore-spacer-receptor molecular structure, form redox active molecular switches, with the photoinduced electron-transfer behavior of each depending on the oxidation state of the receptor subunit. The switch based on nicotinamide (3/6) is strongly fluorescent in its oxidized state (Phi(F) approximately 1.0) but nonfluorescent in the reduced state (Phi(F) < 0.001) due to electron transfer from the reduced nicotinamide to the photoexcited fluorophore. The fluorescence can be reversibly switched off and on chemically by successive reduction with NaBH(3)CN and oxidation with tetrachlorobenzoquinone and switched electrochemically over 10 cycles without significant degradation. A similar switch based on quinonimine turned out to be nonfluorescent in both reduced and oxidized states: in addition to a similar quenching mechanism in the reduced state, quenching also occurs in the oxidized state, due to electron transfer from the fluorophore to the receptor. Ab initio quantum chemical calculations of orbital energy levels were used to corroborate these quenching mechanisms. Calculations predicted photoinduced electron transfer to be energetically favorable in all cases where quenching was observed and unfavorable in all cases where it was not. Application of the perylene analogue as a biosensor has also been demonstrated by coupling the switch to the catalytic pathway of yeast alcohol dehydrogenase, a common NADH/NAD(+)-utilizing enzyme.

Self-organized perylene diimide nanofibers.

A propeller-shaped perylene diimide trimer was synthesized and a simple evaporation method was used for the self-organization of trimer molecules into fluorescent nanofibers. The sizes of these fibers-from 4 to 150 nm in diameter-were measured by atomic force microscopy and can be controlled by adjusting the concentration of the initial solution. The aspect ratios (length/height) are around 500. The plane of the trimer was determined by polarized scanning confocal microscopy to be perpendicular to the axis of the fibers, in agreement with molecular mechanics calculations. UV/vis and NMR spectroscopies were used to monitor concentration-dependent pi-pi stacking in solution. Single-fiber fluorescence imaging and spectroscopy were performed using a total internal reflection fluorescence microscope equipped with a digital color camera and imaging CCD spectrometer. Strongly red-shifted fluorescence from these fibers indicates a high degree of electronic delocalization, and breaking up this delocalization by photobleaching blue-shifts the emission toward that of an isolated noninteracting molecule. The delocalization along these nanofibers and the ability to study the electronic structure using fluorescence make them potentially useful in nanoscale devices, such as field effect transistors and photoconductors.

Studying and switching electron transfer: from the ensemble to the single molecule.

We report here on the systematic investigation of photoinduced intramolecular electron transfer (IET) in a series of donor-bridge-acceptor molecules as a means of understanding electron transport through the bridge. Perylenebisimide chromophores connected by various oligophenylene bridges are studied because their electron-transfer behavior can readily be monitored by following changes in the fluorescence intensity. We find dramatic switching of the IET behavior as the solvent polarity (dielectric constant) is increased. By combining steady-state and time-resolved fluorescence spectroscopy in a variety of solvents at multiple temperatures with standard theories of electron transfer, we determine parameters governing the IET behavior of these dimers, such as the electronic coupling through the bridges. We also deploy available ab initio quantum chemical methods to calculate the through-space component of the electronic coupling matrix element. Single-molecule investigations of the electron-transfer behavior also show that IET can be switched reversibly by a similar mechanism in an isolated individual molecule.

Using single-molecule fluorescence spectroscopy to study electron transfer.

Techniques in single-molecule fluorescence spectroscopy now allow sophisticated studies of photophysical processes in single molecules. As interest grows in the possibilities of molecular electronics, researchers have begun to turn these techniques to the study of electron transfer. Electron-transfer reactions have now been detected and measured at the single-molecule level in a variety of systems and on a variety of timescales by adapting techniques from previous single-molecule fluorescence studies.

Single-molecule spectroscopy of interfacial electron transfer.

It is widely appreciated that single-molecule spectroscopy (SMS) can be used to measure properties of individual molecules which would normally be obscured in an ensemble-averaged measurement. In this report we show how SMS can be used to measure photoinduced interfacial electron transfer (IET) and back electron transfer rates in a prototypical chromophore-bridge-electrode nonadiabatic electron transfer system. N-(1-hexylheptyl)-N'-(12-carboxylicdodecyl)perylene-3,4,9,10-tetracarboxylbisimide was synthesized and incorporated into mixed self-assembled monolayers (SAMs) on an ITO (tin-doped indium oxide, a p-type semiconductor) electrode. Single-molecule fluorescence time trajectories from this system reveals "blinks", momentary losses in fluorescence (>20 ms to seconds in duration), which are attributed to discrete electron transfer events: electron injection from the perylene chromophore into the conduction band of the ITO leads to the loss of fluorescence, and charge recombination (back electron transfer) leads to the return of fluorescence. Such blinks are not observed when an electrode is not present. The fluorescence trajectories were analyzed to obtain the forward and back electron rates; the measured rates are found to lie in the millisecond to second regime. Different rates are observed for different molecules, but the lifetime distributions for the forward or back electron transfer for any given molecule are well fit by single exponential kinetics. The methodology used is applicable to a wide variety of systems and can be used to study the effects of distance, orientation, linker, environment, etc. on electron transfer rates. The results and methodology have implications for molecular electronics, where understanding and controlling the range of possible behaviors inherent to molecular systems will likely be as important as understanding the individual behavior of any given molecule.

A single-molecule probe based on intramolecular electron transfer.

Detecting structure, dynamics, and chemical reactions at the single-molecule level represents the ultimate degree of sensitivity for sensing and imaging. There is a tremendous need to develop new molecular systems and methodology for single-molecule-based sensing. This work presents for the first time the single-molecule spectroscopy of a new molecular probe which uses an intramolecular electron transfer mechanism to detect binding, local structure, and interfacial processes. Moreover, we show how information about the interaction of these probes with their environment is obtained from an analysis of the intensity, duration and time-varying behavior of the single-molecule fluorescence.