Toward robot-assisted vascular microsurgery in the retina

BACKGROUND: Experimental protocol in our laboratory routinely requires the precise placement of instruments at, or near, the retina. Although manipulators for placing an instrument within the eye presently exist, none of the designs were satisfactory due to limitations on size, accuracy and operability. To overcome these limitations, we have developed a novel six degree of freedom manipulator designed specifically for retinal microsurgery. METHODS: The manipulator is parallel in structure and provides submicrometer positioning of an instrument within the constrained environment of the eye. The position of an instrument attached to the manipulator is commanded by the operator using a hand-held trackball. A computer controller interprets the trackball input and moves the manipulator in an intuitive manner according to mathematically constrained modes of operation. RESULTS: Over 50 retinal vessels in the live, anesthetized cat have been successfully cannulated for pressure measurement and drug injection using the described manipulator and micropuncture techniques. The targeted vessels ranged in internal diameter from 20 to 130 microns. CONCLUSION: This device has applications in microsurgery where tremor and fatigue limit the performance of an unaided hand and where mechanically constrained manipulators are inappropriate due to size and operative constraints.     

Understanding metaphorical comparisons: Beyond similarity.

Traditionally, metaphors such as "my job is a jail" have been treated as implicit similes (i.e., this metaphor would be treated as if it were a comparison statement, "my job is like a jail"). A. Tversky's (1977) account of similarity is applied to such nonliteral similarity expressions, and is shown to apply as readily to nonliteral comparisons as to literal comparisons. But treating metaphors as comparison statements fails to account for certain important phenomena, including metaphoricity itself (the judgment that a comparison statement is nonliteral). We argue that metaphors are exactly what they appear to be: class-inclusion assertions, in which the topic of the metaphor (e.g., "my job") is assigned to a diagnostic category (e.g., entities that confine one against one's will, are unpleasant, are difficult to escape from). In such assertions, the metaphor vehicle (e.g., "jail") refers to that category, and at the same time is a prototypical exemplar of that category. This account of metaphor provides a basis for a theory of metaphor comprehension, and also clarifies why people use metaphors instead of similes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Choroidal perfusion measurements made with optical coherence tomography

Choroidal perfusion measurements are complicated by the choroid's location posterior to the retina and its associated retinal blood vessels. Optical coherence tomography is a relatively new imaging technique with sufficient spatial resolution to isolate choroidal backscattering events from the posterior eye. We modified a speckle imaging algorithm to analyze sequential axial depth scans obtained from posterior rat eye to obtain an indicator of choroidal perfusion. This indicator is correlated with known changes in choroidal blood flow in response to increased intraocular pressure.     

Bond-detach lithography: a method for micro/nanolithography by precision PDMS patterning

We have discovered a micro/nanopatterning technique based on the patterning of a PDMS membrane/film, which involves bonding a PDMS structure/stamp (that has the desired patterns) to a PDMS film. The technique, which we call "bond-detach lithography", was demonstrated (in conjunction with other microfabrication techniques) by transferring several micro- and nanoscale patterns onto a variety of substrates. Bond-detach lithography is a parallel process technique in which a master mold can be used many times, and is particularly simple and inexpensive.     

How to be sarcastic: The echoic reminder theory of verbal irony.

Positive statements, such as "A fine friend you are," can readily be used sarcastically. Negative statements, such as "You're a terrible friend," can be used sarcastically only under special circumstances. We account for this asymmetry in terms of echoic reminder theory, which asserts that listeners recognize sarcasm when they perceive that a speaker is alluding to some antecedent state of affairs. Positive statements do not require explicit antecedents because such statements may implicitly allude to societal norms and expectations, and these norms are almost invariably positive. Negative statements, however, cannot implicitly allude to such positive norms, and so they should require explicit antecedents if they are to be understood. An explicit victim of a sarcastically intended remark can provide such an antecedent and so should enable negative statements to be used sarcastically. Three experiments, involving scenarios with and without victims, provide support for this theory of sarcastic irony. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Context can constrain lexical access: Implications for models of language comprehension.

In Exp I, with 20 undergraduates, whether context can constrain lexical access was tested, using an interference version of D. A. Swinney's (see record 1981-04783-001) cross-modal lexical decision paradigm (materials appended). Data indicate that, regardless of relative frequency of use, only the contextually appropriate meanings of the ambiguous primes were activated. In order to assess the degree of equivalence directly in Exp IIa, 24 undergraduates were asked to make lexical decisions on the targets in Exp I but without any auditory context. Results suggest that the effects of context on high-frequency items do not seem to be an artifact of preexisting differences between targets and controls. In Exp IIb, with 24 undergraduates, the possibility of latent differences was examined by presenting the control lexical decision task in a dual task context. Findings demonstrate that differences among visual lexical decision targets and their controls cannot account for the results of Exp I. In general, it is suggested that context can constrain initial meaning activation, limiting lexical access to a single, contextually appropriate sense. Findings support the notion that language comprehension involves interactions among levels of speech and discourse analysis, at least at the level of word recognition. Specifically, lexical information is supplemented by and integrated with sentence-level contextual information to guide and constrain initial stages of word recognition. (47 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

In vivo glucose measurement by surface-enhanced Raman spectroscopy

This paper presents the first in vivo application of surface-enhanced Raman scattering (SERS). SERS was used to obtain quantitative in vivo glucose measurements from an animal model. Silver film over nanosphere surfaces were functionalized with a two-component self-assembled monolayer, and subcutaneously implanted in a Sprague-Dawley rat such that the glucose concentration of the interstitial fluid could be measured by spectroscopically addressing the sensor through an optical window. The sensor had relatively low error (RMSEC = 7.46 mg/dL (0.41 mM) and RMSEP = 53.42 mg/dL (2.97 mM).     

Phase-slope and group-dispersion calculations in the frequency domain by simple optical low-coherence reflectometry

We report a new method by which phase slope and group dispersion can be calculated with a simple optical low-coherence reflectometer to quantify physiological conditions. A discrete-time signal processing algorithm based on the first and second derivatives of the phase with respect to wave number was developed from discrete-time Fourier properties. The algorithm avoids the 2pi ambiguity associated with most phase unwrapping. Experimental data collected by use of well-characterized optical materials validated the algorithm, which was minimally sensitive to phase noise. The group dispersion of bovine cornea was measured at various hydrations and was significantly dependent on hydration. The results suggest that group dispersion is an indicator of corneal alterations.     

Glucose sensing using near-infrared surface-enhanced Raman spectroscopy: gold surfaces, 10-day stability, and improved accuracy

This research presents the achievement of significant milestones toward the development of a minimally invasive, continuously monitoring, glucose-sensing platform based on the optical quantitation of glucose in interstitial fluid. We expand our initial successes in the measurement of glucose by surface-enhanced Raman scattering (SERS), demonstrating substantial improvements not only in the quality and optical properties of the substrate system itself but also in the robustness of the measurement methodology and the amenability of the technique to compact, diode laser-based instrumentation. Herein, we compare the long-term stability of gold to silver film over nanosphere (AuFON, AgFON) substrates functionalized with a partitioning self-assembled monolayer (SAM) using both electrochemical and SERS measurements. AuFONs were found to be stable for a period of at least 11 days. The switch to AuFONs not only provides a more stable surface for SAM formation but also yields better chemometric results, with improved calibration and validation over a range of 0.5-44 mM (10-800 mg/dL). Measured values for glucose concentrations in phosphate-buffered saline (pH approximately 7.4) based on 160 independent SERS measurements on AuFONs have a root-mean-square error of prediction of 2.7 mM (49.5 mg/dL), with 91% of the values falling within an extended A-B range on an expanded Clarke error grid. Furthermore, AuFONs exhibit surface plasmon resonances at longer wavelengths than similar AgFONs, which make them more efficient for SERS at near-infrared wavelengths, enabling the use of low-power diode lasers in future devices.     

Real-time glucose sensing by surface-enhanced Raman spectroscopy in bovine plasma facilitated by a mixed decanethiol/mercaptohexanol partition layer

A new, mixed decanethiol (DT)/mercaptohexanol (MH) partition layer with dramatically improved properties has been developed for glucose sensing by surface-enhanced Raman spectroscopy. This work represents significant progress toward our long-term goal of a minimally invasive, continuous, reusable glucose sensor. The DT/MH-functionalized surface has greater temporal stability, demonstrates rapid, reversible partitioning and departitioning, and is simpler to control compared to the tri(ethylene glycol) monolayer used previously. The data herein show that this DT/MH-functionalized surface is stable for at least 10 days in bovine plasma. Reversibility is demonstrated by exposing the sensor alternately to 0 and 100 mM aqueous glucose solutions (pH approximately 7). The difference spectra show that complete partitioning and departitioning occur. Furthermore, physiological levels of glucose in two complex media were quantified using multivariate analysis. In the first system, the sensor is exposed to a solution consisting of water with 1 mM lactate and 2.5 mM urea. The root-mean-squared error of prediction (RMSEP) is 92.17 mg/dL (5.12 mM) with 87% of the validation points falling within the A and B range of the Clarke error grid. In the second, more complex system, glucose is measured in the presence of bovine plasma. The RMSEP is 83.16 mg/dL (4.62 mM) with 85% of the validation points falling within the A and B range of the Clarke error grid. Finally, to evaluate the real-time response of the sensor, the 1/e time constant for glucose partitioning and departitioning in the bovine plasma environment was calculated. The time constant is 28 s for partitioning and 25 s for departitioning, indicating the rapid interaction between the SAM and glucose that is essential for continuous sensing.