Connecting Adaptive Perceptual Learning and Signal Detection Theory in Skin Cancer Screening.

Combining perceptual learning techniques with adaptive learning algorithms has been shown to accelerate the development of expertise in medical and STEM learning domains (Kellman & Massey, 2013; Kellman, Jacoby, Massey & Krasne, 2022). Virtually all adaptive learning systems have relied on simple accuracy data that does not take into account response bias, a problem that may be especially consequential in multi-category perceptual classifications. We investigated whether adaptive perceptual learning in skin cancer screening can be enhanced by incorporating signal detection theory (SDT) methods that separate sensitivity from criterion. SDT-style concepts were used to alter sequencing, and separately to define mastery (category retirement). SDT retirement used a running d' estimate calculated from a recent window of trials based on hit and false alarm rates. Undergraduate participants used a Skin Cancer PALM (perceptual adaptive learning module) to learn classification of 10 cancerous and readily-confused non-cancerous skin lesion types. Four adaptive conditions varied either the type of adaptive sequencing (standard vs. SDT) or retirement criteria (standard vs. SDT). A non-adaptive control condition presented didactic instruction on dermatologic screening in video form, including images, classification schemes, and detailed explanations. All adaptive conditions robustly outperformed the non-adaptive control in both learning efficiency and fluency (large effect sizes). Between adaptive conditions, SDT retirement criteria produced greater learning efficiency than standard, accuracy-based mastery criteria at both immediate and delayed posttests (medium effect sizes). SDT sequencing and standard adaptive sequencing did not differ. SDT enhancements to adaptive perceptual learning procedures have potential to enhance learning efficiency.

Broadband, millimeter-wave antireflection coatings for large-format, cryogenic aluminum oxide optics.

We present two prescriptions for broadband ($ {\sim} 77 - 252\;{\rm GHz} $), millimeter-wave antireflection coatings for cryogenic, sintered polycrystalline aluminum oxide optics: one for large-format (700 mm diameter) planar and plano-convex elements, the other for densely packed arrays of quasi-optical elements-in our case, 5 mm diameter half-spheres (called "lenslets"). The coatings comprise three layers of commercially available, polytetrafluoroethylene-based, dielectric sheet material. The lenslet coating is molded to fit the 150 mm diameter arrays directly, while the large-diameter lenses are coated using a tiled approach. We review the fabrication processes for both prescriptions, then discuss laboratory measurements of their transmittance and reflectance. In addition, we present the inferred refractive indices and loss tangents for the coating materials and the aluminum oxide substrate. We find that at 150 GHz and 300 K the large-format coating sample achieves $ (97 \pm 2)\% $ transmittance, and the lenslet coating sample achieves $ (94 \pm 3)\% $ transmittance.

Neuro-Ophthalmology in Emergency Medicine.

Understanding the anatomy and physiology of the eye, the orbit, and the central connections is key to understanding neuro-ophthalmologic emergencies. Anisocoria is an important sign that requires a systematic approach to avoid misdiagnosis of serious conditions, including carotid dissection (miosis) and aneurysmal third nerve palsy (mydriasis). Ptosis may be a sign of either Horner syndrome or third nerve palsy. An explanation should be pursued for diplopia since the differential diagnosis ranges from the trivial to life-threatening causes.

Reconfigurable multi-scale colloidal assembly on excluded volume patterns.

The ability to create multi-scale, periodic colloidal assemblies with unique properties is important to emerging applications. Dynamically manipulating colloidal structures via tunable kT-scale attraction can provide the opportunity to create particle-based nano- and microstructured materials that are reconfigurable. Here, we report a novel tactic to obtain reconfigurable, multi-scale, periodic colloidal assemblies by combining thermoresponsive depletant particles and patterned topographical features that, together, reversibly mediate local kT-scale depletion interactions. This method is demonstrated in optical microscopy experiments to produce colloidal microstructures that reconfigure between well-defined ordered structures and disordered fluid states as a function of temperature and pattern feature depth. These results are well described by Monte Carlo simulations using theoretical depletion potentials that include patterned excluded volume. Ultimately, the approach reported here can be extended to control the size, shape, orientation, and microstructure of colloidal assemblies on multiple lengths scales and on arbitrary pre-defined pattern templates.

Gene therapy for radioprotection.

Radiation therapy is a critical component of cancer treatment with over half of patients receiving radiation during their treatment. Despite advances in image-guided therapy and dose fractionation, patients receiving radiation therapy are still at risk for side effects due to off-target radiation damage of normal tissues. To reduce normal tissue damage, researchers have sought radioprotectors, which are agents capable of protecting tissue against radiation by preventing radiation damage from occurring or by decreasing cell death in the presence of radiation damage. Although much early research focused on small-molecule radioprotectors, there has been a growing interest in gene therapy for radioprotection. The amenability of gene therapy vectors to targeting, as well as the flexibility of gene therapy to accomplish ablation or augmentation of biologically relevant genes, makes gene therapy an excellent strategy for radioprotection. Future improvements to vector targeting and delivery should greatly enhance radioprotection through gene therapy.

A fully automated microfluidic femtosecond laser axotomy platform for nerve regeneration studies in C. elegans.

Femtosecond laser nanosurgery has been widely accepted as an axonal injury model, enabling nerve regeneration studies in the small model organism, Caenorhabditis elegans. To overcome the time limitations of manual worm handling techniques, automation and new immobilization technologies must be adopted to improve throughput in these studies. While new microfluidic immobilization techniques have been developed that promise to reduce the time required for axotomies, there is a need for automated procedures to minimize the required amount of human intervention and accelerate the axotomy processes crucial for high-throughput. Here, we report a fully automated microfluidic platform for performing laser axotomies of fluorescently tagged neurons in living Caenorhabditis elegans. The presented automation process reduces the time required to perform axotomies within individual worms to ∼17 s/worm, at least one order of magnitude faster than manual approaches. The full automation is achieved with a unique chip design and an operation sequence that is fully computer controlled and synchronized with efficient and accurate image processing algorithms. The microfluidic device includes a T-shaped architecture and three-dimensional microfluidic interconnects to serially transport, position, and immobilize worms. The image processing algorithms can identify and precisely position axons targeted for ablation. There were no statistically significant differences observed in reconnection probabilities between axotomies carried out with the automated system and those performed manually with anesthetics. The overall success rate of automated axotomies was 67.4±3.2% of the cases (236/350) at an average processing rate of 17.0±2.4 s. This fully automated platform establishes a promising methodology for prospective genome-wide screening of nerve regeneration in C. elegans in a truly high-throughput manner.

kT-Scale interactions between supported lipid bilayers.

We use total internal reflection microscopy (TIRM) and confocal laser scanning microscopy (CSLM) to study supported lipid bilayer (SLB)-modified silica colloids with various SLB compositions (e.g., PEGylated vs. non-PEGylated) that control colloidal and bilayer stability. Measured and predicted potentials accurately capture stable configurations. For unstable conditions when SLBs adhere, fuse, or spread between surfaces, SLB structures are connected to effective potentials as well as time-dependent behavior. In all cases, directly measured and inferred interactions are well described by steric interactions between PEG brushes and van der Waals weakened by substrate roughness. Our findings quantify non-specific kT-scale interactions between SLB-modified colloids and surfaces, which enables the design of such systems for use in biomedical applications and studies of biomolecular interactions.

Phosphate-enhanced cytotoxicity of zinc oxide nanoparticles and agglomerates.

Zinc oxide (ZnO) nanoparticles (NPs) have been found to readily react with phosphate ions to form zinc phosphate (Zn3(PO4)2) crystallites. Because phosphates are ubiquitous in physiological fluids as well as waste water streams, it is important to examine the potential effects that the formation of Zn3(PO4)2 crystallites may have on cell viability. Thus, the cytotoxic response of NIH/3T3 fibroblast cells was assessed following 24h of exposure to ZnO NPs suspended in media with and without the standard phosphate salt supplement. Both particle dosage and size have been shown to impact the cytotoxic effects of ZnO NPs, so doses ranging from 5 to 50 µg/mL were examined and agglomerate size effects were investigated by using the bioinert amphiphilic polymer polyvinylpyrrolidone (PVP) to generate water-soluble ZnO ranging from individually dispersed 4 nm NPs up to micron-sized agglomerates. Cell metabolic activity measures indicated that the presence of phosphate in the suspension media can led to significantly reduced cell viability at all agglomerate sizes and at lower ZnO dosages. In addition, a reduction in cell viability was observed when agglomerate size was decreased, but only in the phosphate-containing media. These metabolic activity results were reflected in separate measures of cell death via the lactate dehydrogenase assay. Our results suggest that, while higher doses of water-soluble ZnO NPs are cytotoxic, the presence of phosphates in the surrounding fluid can lead to significantly elevated levels of cell death at lower ZnO NP doses. Moreover, the extent of this death can potentially be modulated or offset by tuning the agglomerate size. These findings underscore the importance of understanding how nanoscale materials can interact with the components of surrounding fluids so that potential adverse effects of such interactions can be controlled.

Detection of B-mode polarization in the cosmic microwave background with data from the South Pole Telescope.

Gravitational lensing of the cosmic microwave background generates a curl pattern in the observed polarization. This "B-mode" signal provides a measure of the projected mass distribution over the entire observable Universe and also acts as a contaminant for the measurement of primordial gravity-wave signals. In this Letter we present the first detection of gravitational lensing B modes, using first-season data from the polarization-sensitive receiver on the South Pole Telescope (SPTpol). We construct a template for the lensing B-mode signal by combining E-mode polarization measured by SPTpol with estimates of the lensing potential from a Herschel-SPIRE map of the cosmic infrared background. We compare this template to the B modes measured directly by SPTpol, finding a nonzero correlation at 7.7σ significance. The correlation has an amplitude and scale dependence consistent with theoretical expectations, is robust with respect to analysis choices, and constitutes the first measurement of a powerful cosmological observable.

Noise performance of phase-insensitive multicasting in multi-stage parametric mixers.

Noise properties of large-count spectral multicasting in a phase-insensitive parametric mixer were investigated. Scalable multicasting was achieved using two-tone continuous-wave seeded mixers capable of generating more than 20 frequency non-degenerate copies. The mixer was constructed using a multistage architecture to simultaneously manage high Figure-of-Merit frequency generation and suppress noise generation. The performance was characterized by measuring the conversion efficiency and noise figure of all signal copies. Minimum noise figure of 8.09dB was measured. Experimental findings confirm that noise of the multicasted signal does not grow linearly with copy count and that it can be suppressed below this limit.

Towards endoscopic ultrafast laser microsurgery of vocal folds.

Vocal fold scarring is a predominant cause of voice disorders yet lacks a reliable treatment method. The injection of soft biomaterials to improve mechanical compliance of the vocal folds has emerged as a promising treatment. Here, we study the use of precise femtosecond laser microsurgery to ablate subsurface voids, with a goal of eventually creating a plane in dense subepithelial scar tissue into which biomaterials can be injected for their improved localization. Specifically, we demonstrate the ablation of small subepithelial voids in porcine vocal fold tissue up to 120 [micro sign]m below the surface such that larger voids in the active area of vocal fold mucosa (~3×10 mm(2)) can eventually be ablated in about 3 min. We use sub-µJ, 776-nm pulses from a compact femtosecond fiber laser system operating at a 500-kHz repetition rate. The use of relatively high repetition rates, with a small number of overlapping pulses, is critical to achieving ablation in a very short time while still avoiding significant heat deposition. Additionally, we use the same laser for nonlinear optical imaging to provide visual feedback of tissue structure and to confirm successful ablation. The ablation parameters, including pulse duration, pulse energy, spot size, and scanning speed, are comparable to the specifications in our recently developed miniaturized femtosecond laser surgery probes, illustrating the feasibility of developing an ultrafast laser surgical instrument.

Concentrated diffusing colloidal probes of Ca2+-dependent cadherin interactions.

We report video microscopy measurements and inverse simulation analyses of specific Ca(2+)-dependent interactions between N-cadherin fragments attached to supported lipid bilayer-coated silica colloids in quasi-2D concentrated configurations. Our results include characterization of the bilayer formation and fluidity and the attachment of active extracellular cadherin fragments on bilayers. Direct measurements of interaction potentials show nonspecific macromolecular repulsion between cadherin fragments in the absence of Ca(2+) and irreversible bilayer fusion via cadherin-mediated attraction at >100 µM Ca(2+). Analysis of Ca(2+)-dependent N-cadherin bond formation in quasi-2D concentrated configurations using inverse Monte Carlo and Brownian Dynamics simulations show measurable attraction starting at 0.1 µM Ca(2+), a concentration significantly below previously reported values.

Evanescent wave excited luminescence from levitated quantum dot modified colloids.

Evanescent wave excited luminescence of quantum dot modified polystyrene (QDPS) colloids is investigated to measure potential energy profiles of QDPS colloids electrostatically levitated above a planar glass surface. Luminescence is characterized for three different-sized PS colloids modified with three different-sized QDs using confocal microscopy, emission spectra, flow cytometry, and temporal measurements of levitated and deposited colloids. Colloid-surface potential energy profiles constructed from scattering and luminescence intensity data display excellent agreement with each other, theoretical predictions, and independently measured parameters. QDPS luminescence intensity is indirectly confirmed to have an exponential dependence on height similar to conventional colloidal evanescent wave scattering. Our findings indicate that evanescent wave excited QDPS luminescence could enable total internal reflection microscopy measurements of index-matched hard spheres, multiple specific biomolecular interactions via spectral multiplexing, enhanced morphology-dependent resonance modes, and integrated evanescent wave-video-confocal microscopy experiments not possible with scattering.

Diffusing colloidal probes of protein and synthetic macromolecule interactions.

A new approach is described for measuring kT and nanometer scale protein-protein and protein-synthetic macromolecule interactions. The utility of this method is demonstrated by measuring interactions of bovine serum albumin (BSA) and copolymers with exposed polyethyleneoxide (PEO) moieties adsorbed to hydrophobically modified colloids and surfaces. Total internal reflection and video microscopy are used to track three-dimensional trajectories of many single diffusing colloids that are analyzed to yield interaction potentials, mean-square displacements, and colloid-surface association lifetimes. A criterion is developed to identify colloids as being levitated, associated, or deposited based on energetic, spatial, statistical, and temporal information. Whereas levitation and deposition occur for strongly repulsive or attractive potentials, association is exponentially sensitive to weak interactions influenced by adsorbed layer architectures and surface heterogeneity. Systematic experiments reveal how BSA orientation and PEO molecular weight produce adsorbed layers that either conceal or expose substrate heterogeneities to generate a continuum of colloid-surface association lifetimes. These measurements provide simultaneous access to a broad range of information that consistently indicates purely repulsive BSA and PEO interactions and a role for surface heterogeneity in colloid-surface association. The demonstrated capability to measure nonspecific protein interactions provides a basis for future measurements of specific protein interactions.

Mapping patterned potential energy landscapes with diffusing colloidal probes.

We report a new method for mapping patterned surfaces based on monitoring the interactions of freely diffusing colloidal probes with pattern features to generate measured potential energy landscapes. Evanescent wave scattering and video microscopy are used to track 3D center positions of nominal 2 microm silica colloids as they diffuse over 5-20-nm-thick patterned gold films. An analysis of ensemble-averaged particle height histograms on different pattern features using Boltzmann's equation produces local electrostatic and van der Waals potentials in good agreement with independent measurements and predictions. Absolute separation is obtained from theoretical fits to measured potential-energy profiles and direct measurement by depositing silica colloids onto gold surfaces via electrophoretic deposition. As colloidal probe and pattern feature dimensions become comparable, potential energy profiles suffer some distortion due to the increased probability of probes sampling pattern feature edges. An analysis of interfacial colloidal probe diffusion in conjunction with potential energy measurements demonstrates a consistent interpretation of dissipative and conservative forces in these measurements. Future extensions of this work should produce similar approaches for interrogating physical, chemical, and biomolecular heterogeneous/patterned surfaces and structures with diffusing colloidal probes.

Unimolecular rate constants for HX or DX elimination (X = F, Cl) from chemically activated CF3CH2CH2Cl, C2H5CH2Cl, and C2D5CH2Cl: threshold energies for HF and HCl elimination.

Vibrationally activated CF(3)CH(2)CH(2)Cl molecules were prepared with 94 kcal mol(-1) of vibrational energy by the combination of CF(3)CH(2) and CH(2)Cl radicals and with 101 kcal mol(-1) of energy by the combination of CF(3) and CH(2)CH(2)Cl radicals at room temperature. The unimolecular rate constants for elimination of HCl from CF(3)CH(2)CH(2)Cl were 1.2 x 10(7) and 0.24 x 10(7) s(-1) with 101 and 94 kcal mol(-1), respectively. The product branching ratio, k(HCl)/k(HF), was 80 +/- 25. Activated CH(3)CH(2)CH(2)Cl and CD(3)CD(2)CH(2)Cl molecules with 90 kcal mol(-1) of energy were prepared by recombination of C(2)H(5) (or C(2)D(5)) radicals with CH(2)Cl radicals. The unimolecular rate constant for HCl elimination was 8.7 x 10(7) s(-1), and the kinetic isotope effect was 4.0. Unified transition-state models obtained from density-functional theory calculations, with treatment of torsions as hindered internal rotors for the molecules and the transition states, were employed in the calculation of the RRKM rate constants for CF(3)CH(2)CH(2)Cl and CH(3)CH(2)CH(2)Cl. Fitting the calculated rate constants from RRKM theory to the experimental values provided threshold energies, E(0), of 58 and 71 kcal mol(-1) for the elimination of HCl or HF, respectively, from CF(3)CH(2)CH(2)Cl and 54 kcal mol(-1) for HCl elimination from CH(3)CH(2)CH(2)Cl. Using the hindered-rotor model, threshold energies for HF elimination also were reassigned from previously published chemical activation data for CF(3)CH(2)CH(3,) CF(3)CH(2)CF(3), CH(3)CH(2)CH(2)F, CH(3)CHFCH(3), and CH(3)CF(2)CH(3). In an appendix, the method used to assign threshold energies was tested and verified using the combined thermal and chemical activation data for C(2)H(5)Cl, C(2)H(5)F, and CH(3)CF(3).

Medical group adoption of Internet services.

Physician leaders and office-based practicing physicians in medium and large practice organizations were surveyed regarding their use of administrative and clinical systems enabled by the Internet. More than 85% of medical groups reported using one or more Internet-enabled services and 35 reported use of more than five Internet-enabled services, including both business and clinical applications. Physician leaders and practicing physicians identified six Internet-enabled services as "essential" for the future success of their practice and indicated that reduced administrative costs, faster payments, and improved quality of care are the most important benefits derived from Internet-enabled applications. Ninety-six percent of survey respondents estimated that Internet-enabled technologies will have a significant, positive impact on the practice of medicine in general and will improve the quality of care before 2003. The lack of industrywide standards for health information and the inability of current computer systems to exchange information across health care delivery networks were cited as the most important barriers to the adoption of Internet-enabled applications by physicians. Respondents believed that action by the Health Care Financing Administration (HCFA) or major health plans to require participating physicians to use the Internet for administrative services will be needed to bring about rapid migration to Internet-enabled services.