Improving Indwelling Glucose Sensor Performance: Porous, Dexamethasone-Releasing Coatings that Modulate the Foreign Body Response

Inflammation and the formation of an avascular fibrous capsule have been identified as the key factors controlling the wound healing associated failure of implantable glucose sensors. Our aim is to guide advantageous tissue remodeling around implanted sensor leads by the temporal release of dexamethasone (Dex), a potent anti-inflammatory agent, in combination with the presentation of a stable textured surface.

First, Dex-releasing polyurethane porous coatings of controlled pore size and thickness were fabricated using salt-leaching/gas-foaming technique. Porosity, pore size, thickness, drug release kinetics, drug loading amount, and drug bioactivity were evaluated. In vitro sensor functionality test were performed to determine if Dex-releasing porous coatings interfered with sensor performance (increased signal attenuation and/or response times) compared to bare sensors. Drug release from coatings monitored over two weeks presented an initial fast release followed by a slower release. Total release from coatings was highly dependent on initial drug loading amount. Functional in vitro testing of glucose sensors deployed with porous coatings against glucose standards demonstrated that highly porous coatings minimally affected signal strength and response rate. Bioactivity of the released drug was determined by monitoring Dex-mediated, dose-dependent apoptosis of human peripheral blood derived monocytes in culture.

The tissue modifying effects of Dex-releasing porous coatings were accessed by fully implanting Tygon® tubing in the subcutaneous space of healthy and diabetic rats. Based on encouraging results from these studies, we deployed Dex-releasing porous coatings from the tips of functional sensors in both diabetic and healthy rats. We evaluated if the tissue modifying effects translated into accurate, maintainable and reliable sensor signals in the long-term. Sensor functionality was accessed by continuously monitoring glucose levels and performing acute glucose challenges at specified time points.

Sensors treated with porous Dex-releasing coatings showed diminished inflammation and enhanced vascularization of the tissue surrounding the implants in healthy rats. Functional sensors with Dex-releasing porous coatings showed enhanced sensor sensitivity over a 21-day period when compared to controls. Enhanced sensor sensitivity was accompanied with an increase in sensor signal lag and MARD score. These results indicated that Dex-loaded porous coatings were able to elicit a favorable tissue response, and that such tissue microenvironment could be conducive towards extending the performance window of glucose sensors in vivo.

The diabetic pilot animal study showed differences in wound healing patters between healthy and diabetic subjects. Diabetic rats showed lower levels of inflammation and vascularization of the tissue surrounding implants when compared to their healthy counterparts. Also, functional sensors treated with Dex-releasing porous coatings did not show enhanced sensor sensitivity over a 21-day period. Moreover, increased in sensor signal lag and MARD scores were present in porous coated sensors regardless of Dex-loading when compared to bare implants. These results suggest that the altered wound healing patterns presented in diabetic tissues may lead to premature sensor failure when compared to sensors implanted in healthy rats.

The neural dynamics of stimulus and response conflict processing as a function of response complexity and task demands.

Both stimulus and response conflict can disrupt behavior by slowing response times and decreasing accuracy. Although several neural activations have been associated with conflict processing, it is unclear how specific any of these are to the type of stimulus conflict or the amount of response conflict. Here, we recorded electrical brain activity, while manipulating the type of stimulus conflict in the task (spatial [Flanker] versus semantic [Stroop]) and the amount of response conflict (two versus four response choices). Behaviorally, responses were slower to incongruent versus congruent stimuli across all task and response types, along with overall slowing for higher response-mapping complexity. The earliest incongruency-related neural effect was a short-duration frontally-distributed negativity at ~200 ms that was only present in the Flanker spatial-conflict task. At longer latencies, the classic fronto-central incongruency-related negativity 'N(inc)' was observed for all conditions, but was larger and ~100 ms longer in duration with more response options. Further, the onset of the motor-related lateralized readiness potential (LRP) was earlier for the two vs. four response sets, indicating that smaller response sets enabled faster motor-response preparation. The late positive complex (LPC) was present in all conditions except the two-response Stroop task, suggesting this late conflict-related activity is not specifically related to task type or response-mapping complexity. Importantly, across tasks and conditions, the LRP onset at or before the conflict-related N(inc), indicating that motor preparation is a rapid, automatic process that interacts with the conflict-detection processes after it has begun. Together, these data highlight how different conflict-related processes operate in parallel and depend on both the cognitive demands of the task and the number of response options.

Recommendations on the nature of the passenger response time distribution to be used in the MSC 1033 assembly time analysis based on data derived from sea trials

The passenger response time distributions adopted by the International Maritime Organisation (IMO)in their assessment of the assembly time for passanger ships involves two key assumptions. The first is that the response time distribution assumes the form of a uniform random distribution and the second concerns the actual response times. These two assumptions are core to the validity of the IMO analysis but are not based on real data, being the recommendations of an IMO committee. In this paper, response time data collected from assembly trials conducted at sea on a real passanger vessel using actual passangers are presented and discussed. Unlike the IMO specified response time distributions, the data collected from these trials displays a log-normal distribution, similar to that found in land based environments. Based on this data, response time distributions for use in the IMO assesmbly for the day and night scenarios are suggested

Investigating the impact of occupant response time on computer simulations of the WTC North Tower evacuation

This work explores the impact of response time distributions on high-rise building evacuation. The analysis utilises response times extracted from printed accounts and interviews of evacuees from the WTC North Tower evacuation of 11 September 2001. Evacuation simulations produced using these “real” response time distributions are compared with simulations produced using instant and engineering response time distributions. Results suggest that while typical engineering approximations to the response time distribution may produce reasonable evacuation times for up to 90% of the building population, using this approach may underestimate total evacuation times by as much as 61%. These observations are applicable to situations involving large high-rise buildings in which travel times are generally expected to be greater than response times

Fast response to human voices in autism

Individuals with autism spectrum disorders (ASD) are reported to allocate less spontaneous attention to voices. Here, we investigated how vocal sounds are processed in ASD adults, when those sounds are attended. Participants were asked to react as fast as possible to target stimuli (either voices or strings) while ignoring distracting stimuli. Response times (RTs) were measured. Results showed that, similar to neurotypical (NT) adults, ASD adults were faster to recognize voices compared to strings. Surprisingly, ASD adults had even shorter RTs for voices than the NT adults, suggesting a faster voice recognition process. To investigate the acoustic underpinnings of this effect, we created auditory chimeras that retained only the temporal or the spectral features of voices. For the NT group, no RT advantage was found for the chimeras compared to strings: both sets of features had to be present to observe an RT advantage. However, for the ASD group, shorter RTs were observed for both chimeras. These observations indicate that the previously observed attentional deficit to voices in ASD individuals could be due to a failure to combine acoustic features, even though such features may be well represented at a sensory level.

Analysis of water-level response to rainfall and implications for recharge pathways in the Chalk aquifer, SE England

Water table response to rainfall was investigated at six sites in the Upper, Middle and Lower Chalk of southern England. Daily time series of rainfall and borehole water level were cross-corretated to investigate seasonal variations in groundwater-level response times, based on periods of 3-month duration. The time tags (in days) yielding significant correlations were compared with the average unsaturated zone thickness during each 3-month period. In general, for cases when the unsaturated zone was greater than 18 m thick, the time tag for a significant water-level response increased rapidly once the depth to the water table exceeded a critical value, which varied from site to site. For shallower water tables, a linear relationship between the depth to the water table and the water-level response time was evident. The observed variations in response time can only be partially accounted for using a diffusive model for propagation through the unsaturated matrix, suggesting that some fissure flow was occurring. The majority of rapid responses were observed during the winter/spring recharge period, when the unsaturated zone is thinnest and the unsaturated zone moisture content is highest, and were more likely to occur when the rainfall intensity exceeded 5 mm/day. At some sites, a very rapid response within 24 h of rainfall was observed in addition to the longer term responses even when the unsaturated zone was up to 64 m thick. This response was generally associated with the autumn period. The results of the cross-correlation analysis provide statistical support for the presence of fissure flow and for the contribution of multiple pathways through the unsaturated zone to groundwater recharge. (c) 2006 Elsevier B.V. All rights reserved.

Demand response from the non-domestic sector: early UK experiences and future opportunities

Demand response is believed by some to become a major contributor towards system balancing in future electricity networks. Shifting or reducing demand at critical moments can reduce the need for generation capacity, help with the integration of renewables, support more efficient system operation and thereby potentially lead to cost and carbon reductions for the entire energy system. In this paper we review the nature of the response resource of consumers from different non-domestic sectors in the UK, based on extensive half hourly demand profiles and observed demand responses. We further explore the potential to increase the demand response capacity through changes in the regulatory and market environment. The analysis suggests that present demand response measures tend to stimulate stand-by generation capacity in preference to load shifting and we propose that extended response times may favour load based demand response, especially in sectors with significant thermal loads.

Demand side response: patterns in Europe and future policy perspectives under capacity mechanisms

Demand Side Response (DSR) has been slow to emerge in European electricity markets. This paper aims to both examine the reasons for low levels of DSR in Europe and reflect on factors that might affect the participation of DSR in capacity mechanisms. It relies on available evidence from the literature, secondary data on existing DSR programmes and energy aggregator's data from industries participating in DSR. Findings show that changes to the duration of contracted loads under existing or new programmes might increase the penetration of DSR. The introduction of capacity mechanisms may increase DSR from demand turn down if longer response times were available.

Automotive can network response time analysis with variable jitter

Many methods to calculate message latencies for Controller Area Network (CAN) have previously been presented based upon the static worst-case behaviour of the system. With the use of modern simulation tools however, the behaviour of CAN networks can be simulated dynamically in order to find the likely worst-case response times for CAN messages. This paper shows the development of an automotive body control network model to be used as the basis for further simulations. A method to simulate the Worst-Case Response Time of this model is then presented, taking into account random queuing jitter.

Determining the sensitivity of the Antarctic amphipod Orchomenella pinguides to metals using a joint model of survival response to exposure concentration and duration

Developing water quality guidelines for Antarctic marine environments requires understanding the sensitivity of local biota to contaminant exposure. Antarctic invertebrates have shown slower contaminant responses in previous experiments compared to temperate and tropical species in standard toxicity tests. Consequently, test methods which take into account environmental conditions and biological characteristics of cold climate species need to be developed. This study investigated the effects of five metals on the survival of a common Antarctic amphipod, Orchomenella pinguides. Multiple observations assessing mortality to metal exposure were made over the 30 days exposure period. Traditional toxicity tests with quantal data sets are analysed using methods such as maximum likelihood regression (probit analysis) and Spearman–Kärber which treat individual time period endpoints independently. A new statistical model was developed to integrate the time-series concentration–response data obtained in this study. Grouped survival data were modelled using a generalized additive mixed model (GAMM) which incorporates all the data obtained from multiple observation times to derive time integrated point estimates. The sensitivity of the amphipod, O. pinguides, to metals increased with increasing exposure time. Response times varied for different metals with amphipods responding faster to copper than to cadmium, lead or zinc. As indicated by 30 days lethal concentration (LC50) estimates, copper was the most toxic metal (31 µg/L), followed by cadmium (168 µg/L), lead (256 µg/L) and zinc (822 µg/L). Nickel exposure (up to 1.12 mg/L) did not affect amphipod survival. Using longer exposure durations and utilising the GAMM model provides an improved methodology for assessing sensitivities of slow responding Antarctic marine invertebrates to contaminants.

Sol-gel synthesis of mesoporous CaCu3Ti4O12 thin films and their gas sensing response

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Antimony glasses with large nonlinear refractive indices, small two-photon absorption coefficients and ultrafast response at telecom wavelengths

Nonlinear (NL) optical properties of antimony oxide based glasses (AG) were characterized for excitation wavelengths from 800 to 1600 m. The NL refractive indices, n2, and the two-photon absorption (TPA) coefficient, β, have been evaluated using the Z-scan technique. Values of n2≈ 10-15 - 10-14 cm2/W of electronic origin were measured and negligible TPA coefficients (β < 0.003 cm/GW) were determined. The response time of the nonlinearity is faster than 100 fs as determined using the Kerr shutter technique. The figure-of-merit usually considered for all-optical switching, T = 2βλ/n2 , indicates that AG are very good materials for ultrafast switches at telecom wavelengths. © 2007 IEEE.

Sensitivity and rapidity of vegetational response to abrupt climate change

Rapid climate change characterizes numerous terrestrial sediment records during and since the last glaciation. Vegetational response is best expressed in terrestrial records near ecotones, where sensitivity to climate change is greatest, and response times are as short as decades.

Automaticity in L2 learning: Correlation between vocabulary proficiency and response time in word recognition

Automaticity (in this essay defined as short response time) and fluency in language use are closely connected to each other and some research has been conducted regarding some of the aspects involved. In fact, the notion of automaticity is still debated and many definitions and opinions on what automaticity is have been suggested (Andersson,1987, 1992, 1993, Logan, 1988, Segalowitz, 2010). One aspect that still needs more research is the correlation between vocabulary proficiency (a person’s knowledge about words and ability to use them correctly) and response time in word recognition. Therefore, the aim of this study has been to investigate this correlation using two different tests; one vocabulary size test (Paul Nation) and one lexical decision task (SuperLab) that measures both response time and accuracy. 23 Swedish students partaking in the English 7 course in upper secondary Swedish school were tested. The data were analyzed using a quantitative method where the average values and correlations from the test were used to compare the results. The correlations were calculated using Pearson’s Coefficient Correlations Calculator. The empirical study indicates that vocabulary proficiency is not strongly correlated with shorter response times in word recognition. Rather, the data indicate that L2 learners instead are sensitive to the frequency levels of the vocabulary. The accuracy (number of correct recognized words) and response times correlate with the frequency level of the tested words. This indicates that factors other than vocabulary proficiency are important for the ability to recognize words quickly.

Assessing personal financial management in patients with bipolar disorder and its relation to impulsivity and response inhibition

Introduction: Impulsivity and risk-taking behaviours are reported in bipolar disorder (BD). We examined whether financial management skills are related to impulsivity in patients with BD. Methods: We assessed financial management skills using the Executive Personal Finance Scale (EPFS), impulsivity using the Barratt Impulsiveness Scale (BIS) and response inhibition using an emotional go/no-go task in bipolar individuals (N = 21) and healthy controls (HC; N = 23). Results: Patients had fewer financial management skills and higher levels of impulsivity than HC. In patients and controls, increased impulsivity was associated with poorer personal financial management. Patients and HC performed equally on the emotional go/no-go task. Higher BIS scores were associated with faster reaction times in HC. In patients, however, higher BIS scores were associated with slower reaction times, possibly indicating compensatory cognitive strategies to counter increased impulsivity. Conclusions: Patients with BD may have reduced abilities to manage personal finances, when compared against healthy participants. Difficulty with personal finance management may arise in part as a result of increased levels of impulsivity. Patients may learn to compensate for increased impulsivity by modulating response times in our experimental situations although whether such compensatory strategies generalize to real-world situations is unknown.