Visual search for reach targets in actionable space is influenced by movement costs imposed by obstacles.

Real world search tasks often involve action on a target object once it has been located. However, few studies have examined whether movement-related costs associated with acting on located objects influence visual search. Here, using a task in which participants reached to a target object after locating it, we examined whether people take into account obstacles that increase movement-related costs for some regions of the reachable search space but not others. In each trial, a set of 36 objects (4 targets and 32 distractors) were displayed on a vertical screen and participants moved a cursor to a target after locating it. Participants had to fixate on an object to determine whether it was a target or distractor. A rectangular obstacle, of varying length, location, and orientation, was briefly displayed at the start of the trial. Participants controlled the cursor by moving the handle of a robotic manipulandum in a horizontal plane. The handle applied forces to simulate contact between the cursor and the unseen obstacle. We found that search, measured using eye movements, was biased to regions of the search space that could be reached without moving around the obstacle. This result suggests that when deciding where to search, people can incorporate the physical structure of the environment so as to reduce the movement-related cost of subsequently acting on the located target.

The influence of movement-related costs when searching to act and acting to search.

Real-world search behavior often involves limb movements, either during search or after search. Here we investigated whether movement-related costs influence search behavior in two kinds of search tasks. In our visual search tasks, participants made saccades to find a target object among distractors and then moved a cursor, controlled by the handle of a robotic manipulandum, to the target. In our manual search tasks, participants moved the cursor to perform the search, placing it onto objects to reveal their identity as either a target or a distractor. In all tasks, there were multiple targets. Across experiments, we manipulated either the effort or time costs associated with movement such that these costs varied across the search space. We varied effort by applying different resistive forces to the handle, and we varied time costs by altering the speed of the cursor. Our analysis of cursor and eye movements during manual and visual search, respectively, showed that effort influenced manual search but did not influence visual search. In contrast, time costs influenced both visual and manual search. Our results demonstrate that, in addition to perceptual and cognitive factors, movement-related costs can also influence search behavior.NEW & NOTEWORTHY Numerous studies have investigated the perceptual and cognitive factors that influence decision making about where to look, or move, in search tasks. However, little is known about how search is influenced by movement-related costs associated with acting on an object once it has been visually located or acting during manual search. In this article, we show that movement time costs can bias visual and manual search and that movement effort costs bias manual search.

Evaluation of portable vibrational spectroscopy for identifying plasticizers in dairy tubing.

Plasticisers are commonly used to increase the flexibility of a wide variety of food contact materials including the plastic tubing, liners, and gaskets used in the dairy industry. In recent years, some classes of plasticisers have come under scrutiny due to the potential for transfer of these compounds into the milk itself, which can then be further processed into foods such as powdered milks and cheeses, infant formula, and baked goods. One such set of plasticisers that is being evaluated for frequency of use, potential routes of exposure, and risk to consumers is ortho-phthalates, hereafter referred to as phthalates. In order to better understand the actual use of phthalate versus non-phthalate plasticised tubing, a robust, rapid, and portable analytical method is necessary for on-site screening. Laboratory Raman and near-infrared spectrometers have been used extensively for polymer and additive evaluation, and advances in portable/hand-held technology could lead to feasible plasticiser evaluation in the field. This research overviews efforts to evaluate six portable spectroscopy devices for their ability to identify phthalate versus non-phthalate plasticised polyvinyl chloride (PVC) dairy tubing, liners, and gaskets. The most successful method, a hand-held Raman spectrometer along with a plasticiser spectral library or a chemometric model, can rapidly and accurately identify phthalate containing PVC and has the potential to be employed as a future field screening technique for regulators and the dairy industry.

The Inverse Relationship between Metal-Enhanced Fluorescence and Fluorophore-Induced Plasmonic Current.

In this work we investigate the relationship between metal-enhanced fluorescence (MEF) and fluorophore-induced plasmonic current (PC). This is accomplished through measurements of both radiative emission (MEF) and direct electrical current generation between discrete metal nanoparticles upon fluorophore excitation (PC). We have conducted these measurements on silver and gold nanoparticle island films, over a range of nanoparticle sizes and spacing in the films. We have observed an inverse relationship in the magnitude of MEF with PC, where larger and more closely spaced metal nanoparticles are found to result in increased PC and subsequently a decreased MEF. We attribute this effect to the relatively high capacitance and low charging energy of large and closely spaced particles, providing an outlet for plasmon relaxation in the form of electron flow and electrical current generation. These results are significant as they open potential for controlling for and the optimization of both MEF and PC.

Fluorophore-Induced Plasmonic Current: Generation-Based Detection of Singlet Oxygen.

In this work, we report the surface-based electrical detection of singlet oxygen using the emerging fluorophore-induced plasmonic current (PC) technique. By this method, we utilize the fluorescent "turn on" response of the well-known singlet oxygen sensor green (SOSG) singlet oxygen (1O2) fluorescent probe for the generation of fluorophore-induced PC in a silver nanoparticle film. To demonstrate the potential utility of this new technique, a photosensitizing molecule is used to generate 1O2 in a solution containing the SOSG probe. The resulting change in SOSG fluorescence quantum yield and extinction coefficient permits stronger energy transfer from the SOSG probe to a proximal silver nanoparticle island film located in the near-electric field of the probe. This yields an increase in the induced electric current flow, allowing for the detection of the 1O2 analyte. To the author's knowledge, this represents the first detection of the reactive oxygen species 1O2 utilizing fluorophore-induced PC methodology and even broader electrical detection of 1O2. This is significant as it opens the possibility for 1O2 detection methods which do not require a traditional "photodetector" and associated optics, simplifying the instrumentation over existing fluorescence detection methods and potentially even lowering the cost.

Human decision making anticipates future performance in motor learning.

It is well-established that people can factor into account the distribution of their errors in motor performance so as to optimize reward. Here we asked whether, in the context of motor learning where errors decrease across trials, people take into account their future, improved performance so as to make optimal decisions to maximize reward. One group of participants performed a virtual throwing task in which, periodically, they were given the opportunity to select from a set of smaller targets of increasing value. A second group of participants performed a reaching task under a visuomotor rotation in which, after performing a initial set of trials, they selected a reward structure (ratio of points for target hits and misses) for different exploitation horizons (i.e., numbers of trials they might be asked to perform). Because movement errors decreased exponentially across trials in both learning tasks, optimal target selection (task 1) and optimal reward structure selection (task 2) required taking into account future performance. The results from both tasks indicate that people anticipate their future motor performance so as to make decisions that will improve their expected future reward.

Multicenter evaluation of the thermo scientific prelude for measurement of immunosuppressant drugs using sample preparation liquid chromatography-tandem mass spectrometry.

Immunosuppressant drugs (ISDs) are commonly prescribed to solid organ transplant patients. Their narrow therapeutic index and potential for toxicity necessitates careful monitoring of blood concentrations. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods are increasingly used for ISD measurement. However, there remain many challenges with this methodology, particularly regarding interassay variability. The Thermo Scientific Prelude is an online extraction/liquid chromatography platform that uses turbulent flow technology coupled with MS/MS. A multicenter evaluation of the Prelude for the measurement of cyclosporine A, tacrolimus, and sirolimus is described. ISDs were measured at each site using standardized protocols. Sample preparation liquid chromatography-MS/MS was performed using the Prelude coupled to a TSQ Vantage. Chromatography was achieved with a Cyclone-P TurboFlow/Accucore C8 column combination using a multisolvent loading and eluting pump system. Mass spectrometry acquisitions were performed in selective reaction monitoring mode and data processed using TraceFinder (version 3.1). Multisite mean imprecision for cyclosporine A ranged from 8.8% (54 mcg/L) to 9.8% (450 mcg/L); for tacrolimus, 4.7% (15.5 mcg/L) to 12.6% (2.5 mcg/L); for sirolimus, 7.4% (19.9 mcg/L) to 16.5% (2.6 mcg/L). Approximately 110 specimens were used for method comparison. For cyclosporine A, mean bias against the multisite mean ranged from -18% to 1%; for tacrolimus, values ranged from -7% to 4%; for sirolimus, values ranged from -4% to 2%. Comparisons of multisite mean Prelude results with routine ISD method results was also performed for cyclosporine A (slope = 0.7878, intercept = 24.16, r = 0.98), tacrolimus (slope = 0.9391, intercept = 0.1017, r = 98), and sirolimus (slope = 0.9618, intercept = 0.1483, r = 0.97). The Prelude ISD method offers acceptable and comparable multisite performance. This study has also highlighted the importance of adopting standardized protocols and LC-MS/MS methods for better comparability between ISD assays.

Visual attention to features by associative learning.

Expecting a particular stimulus can facilitate processing of that stimulus over others, but what is the fate of other stimuli that are known to co-occur with the expected stimulus? This study examined the impact of learned association on feature-based attention. The findings show that the effectiveness of an uninformative color transient in orienting attention can change by learned associations between colors and the expected target shape. In an initial acquisition phase, participants learned two distinct sequences of stimulus-response-outcome, where stimuli were defined by shape ('S' vs. 'H'), responses were localized key-presses (left vs. right), and outcomes were colors (red vs. green). Next, in a test phase, while expecting a target shape (80% probable), participants showed reliable attentional orienting to the color transient associated with the target shape, and showed no attentional orienting with the color associated with the alternative target shape. This bias seemed to be driven by learned association between shapes and colors, and not modulated by the response. In addition, the bias seemed to depend on observing target-color conjunctions, since encountering the two features disjunctively (without spatiotemporal overlap) did not replicate the findings. We conclude that associative learning - likely mediated by mechanisms underlying visual object representation - can extend the impact of goal-driven attention to features associated with a target stimulus.

The development and validation of a turbulent flow-liquid chromatography-tandem mass spectrometric method for the simultaneous quantification of citalopram, sertraline, bupropion and hydroxybupropion in serum.

OBJECTIVES: Depression is a rapidly growing issue in the United States. There are many drug classes that may be used to treat depression, including the selective serotonin-reuptake inhibitors (SSRIs) citalopram (Celexa®) and sertraline (Zoloft®), as well as the aminoketone bupropion (Wellbutrin®). However, therapeutic efficacy and treatment success is often variable, requiring changes in dosing regimens or drug selection. Methods for drug quantification can become important tools in the assessment of drug efficacy to optimize treatment regimens. Here, we present a turbulent flow-liquid chromatography-tandem mass spectrometric (TFC-MS/MS) method for the robust, simultaneous quantification of citalopram, sertraline, bupropion and its active metabolite, hydroxybupropion (OH-bupropion). DESIGN AND METHODS: Serum spiked with the aforementioned antidepressants, along with their corresponding isotopically labeled internal standards was subjected to protein precipitation. Samples were injected onto a TFC column for on-line solid phase extraction and a Hypersil Gold C18 column for chromatographic separation. Detection was achieved using a TSQ Vantage mass spectrometer. Assay validation followed FDA bioanalytical guidelines. RESULTS: The analytical measuring range for all analytes spanned from 5 to 1000ng/mL. Intra- and inter-assay precision across four quality control levels were ≤9.2% and ≤14.8%, respectively. A comparison to other LC-MS/MS methods resulted in a strong correlation with correlation coefficients ranging from 0.9929 to 0.9971. Carryover, stability, recovery, matrix effects, extraction and processing efficiency were also deemed acceptable in accordance with FDA recommendations. CONCLUSIONS: The development and validation of this TFC-MS/MS method allow for the robust and high-throughput quantification of commonly prescribed antidepressants.

Surface-mediated bone tissue morphogenesis from tunable nanolayered implant coatings.

The functional success of a biomedical implant critically depends on its stable bonding with the host tissue. Aseptic implant loosening accounts for more than half of all joint replacement failures. Various materials, including metals and plastic, confer mechanical integrity to the device, but often these materials are not suitable for direct integration with the host tissue, which leads to implant loosening and patient morbidity. We describe a self-assembled, osteogenic, polymer-based conformal coating that promotes stable mechanical fixation of an implant in a surrogate rodent model. A single modular, polymer-based multilayered coating was deposited using a water-based layer-by-layer approach, by which each element was introduced on the surface in nanoscale layers. Osteoconductive hydroxyapatite (HAP) and osteoinductive bone morphogenetic protein-2 (BMP-2) contained within the nanostructured coating acted synergistically to induce osteoblastic differentiation of endogenous progenitor cells within the bone marrow, without indications of a foreign body response. The tuned release of BMP-2, controlled by a hydrolytically degradable poly(ß-amino ester), was essential for tissue regeneration, and in the presence of HAP, the modular coating encouraged the direct deposition of highly cohesive trabecular bone on the implant surface. In vivo, the bone-implant interfacial tensile strength was significantly higher than standard bioactive bone cement, did not fracture at the interface, and had long-term stability. Collectively, these results suggest that the multilayered coating system promotes biological fixation of orthopedic and dental implants to improve surgical outcomes by preventing loosening and premature failure.

Ideomotor perception modulates visuospatial cueing.

The ideomotor theory of action posits that the cognitive representation of an action includes the learned perceptual effects of the action. Support for this theory has come from studies demonstrating how perceptual features that match the outcome of a response can facilitate selection of that response. We investigated another, complementary implication of ideomotor theory: would a bias toward selecting a response result in a perceptual bias toward the known effect of the response? In other words, would an action tendency direct attention to the anticipated perceptual features? Through an initial acquisition phase, participants learned that two possible responses (left/right keypress) consistently produced two distinct colors. Next, in a test phase, we manipulated response bias at the beginning of each trial, using an uninformative spatial prime presented at the left or right periphery. We then examined the extent to which color transients that either matched or mismatched the induced response bias can orient participants' visual attention. Results revealed a perceptual bias toward the color effect of the primed response, manifested in a stronger visual orienting toward this color. Thus, biasing response selection can bias perception. These findings extend the scope of the ideomotor theory to visual perceptual processes.

Dual functional polyelectrolyte multilayer coatings for implants: permanent microbicidal base with controlled release of therapeutic agents.

Here we present a new bifunctional layer-by-layer (LbL) construct made by combining a permanent microbicidal polyelectrolyte multilayered (PEM) base film with a hydrolytically degradable PEM top film that offers controlled and localized delivery of therapeutics. Two degradable film architectures are presented: (1) bolus release of an antibiotic (gentamicin) to eradicate initial infection at the implant site, or (2) sustained delivery of an anti-inflammatory drug (diclofenac) to cope with inflammation at the site of implantation due to tissue injury. Each degradable film was built on top of a permanent base film that imparts the implantable device surface with microbicidal functionality that prevents the formation of biofilms. Controlled-delivery of gentamicin was demonstrated over hours and that of diclofenac over days. Both drugs retained their efficacy upon release. The permanent microbicidal base film was biocompatible with A549 epithelial cancer cells and MC3T3-E1 osteoprogenitor cells, while also preventing bacteria attachment from turbid media for the entire duration of the two weeks studied. The microbicidal base film retains its functionality after the biodegradable films have completely degraded. The versatility of these PEM films and their ability to prevent biofilm formation make them attractive as coatings for implantable devices.

The effectiveness of the controlled release of gentamicin from polyelectrolyte multilayers in the treatment of Staphylococcus aureus infection in a rabbit bone model.

While the infection rate of orthopedic implants is low, the required treatment, which can involve six weeks of antibiotic therapy and two additional surgical operations, is life threatening and expensive, and thus motivates the development of a one-stage re-implantation procedure. Polyelectrolyte multilayers incorporating gentamicin were fabricated using the layer-by-layer deposition process for use as a device coating to address an existing bone infection in a direct implant exchange operation. The films eluted about 70% of their payload in vitro during the first three days and subsequently continued to release drug for more than four additional weeks, reaching a total average release of over 550 microg/cm(2). The coatings were demonstrated to be bactericidal against Staphylococcus aureus, and degradation products were generally nontoxic towards MC3T3-E1 murine preosteoblasts. Film-coated titanium implants were compared to uncoated implants in an in vivo S. aureus bone infection model. After a direct exchange procedure, the antimicrobial-coated devices yielded bone homogenates with a significantly lower degree of infection than uncoated devices at both day four (p < 0.004) and day seven (p < 0.03). This study has demonstrated that a self-assembled ultrathin film coating is capable of effectively treating an experimental bone infection in vivo and lays the foundation for development of a multi-therapeutic film for optimized, synergistic treatment of pain, infection, and osteomyelitis.

Electrically Triggered Release of a Small Molecule Drug from a Polyelectrolyte Multilayer Coating.

Electrically triggered drug delivery represents an attractive option for actively and remotely controlling the release of a therapeutic from an implantable device (e.g., a "pharmacy-on-a-chip"). Here we report the fabrication of nanoscale thin films that can release precise quantities of a small molecule drug in response to application of a small, anodic electric potential of at least +0.5 V versus Ag/AgCl. Films containing negatively charged Prussian Blue (PB) nanoparticles and positively charged gentamicin, a small hydrophilic antibiotic, were fabricated using layer-by-layer (LbL) assembly. When oxidized, the PB nanoparticles shift from negatively charged to neutral, inducing dissolution of the film. Films with thicknesses in the range 100-500 nm corresponding to drug loadings of 1-4 µg/cm(2) were characterized. We demonstrate control over the drug dosage by tuning the film thickness as well as the magnitude of the applied voltage. Drug release kinetics ranging from triggered burst release to on/off, or pulsatile release, were achieved by applying different electric potential profiles. Finally, the in vitro efficacy of the released drug was confirmed against Staphylococcus aureus bacteria. Given the versatility of an external electrical stimulus and the ability of LbL assembly to conformally coat a variety of substrates regardless of size, shape, or chemical composition, we maintain that electrically controlled release of a drug from an LbL-coated surface could have applications in both implantable medical devices and transdermal drug delivery systems.