An algorithm for diagnosing IgE-mediated food allergy in study participants who do not undergo food challenge.

BACKGROUND: Food allergy diagnosis in clinical studies can be challenging. Oral food challenges (OFC) are time-consuming, carry some risk and may, therefore, not be acceptable to all study participants. OBJECTIVE: To design and evaluate an algorithm for detecting IgE-mediated food allergy in clinical study participants who do not undergo OFC. METHODS: An algorithm for trial participants in the Barrier Enhancement for Eczema Prevention (BEEP) study who were unwilling or unable to attend OFC was developed. BEEP is a pragmatic, multi-centre, randomized-controlled trial of daily emollient for the first year of life for primary prevention of eczema and food allergy in high-risk infants (ISRCTN21528841). We built on the European iFAAM consensus guidance to develop a novel food allergy diagnosis algorithm using available information on previous allergenic food ingestion, food reaction(s) and sensitization status. This was implemented by a panel of food allergy experts blind to treatment allocation and OFC outcome. We then evaluated the algorithm's performance in both BEEP and Enquiring About Tolerance (EAT) study participants who did undergo OFC. RESULTS: In 31/69 (45%) BEEP and 44/55 (80%) EAT study control group participants who had an OFC the panel felt confident enough to categorize children as "probable food allergy" or "probable no food allergy". Algorithm-derived panel decisions showed high sensitivity 94% (95%CI 68, 100) BEEP; 90% (95%CI 72, 97) EAT and moderate specificity 67% (95%CI 39, 87) BEEP; 67% (95%CI 39, 87) EAT. Sensitivity and specificity were similar when all BEEP and EAT participants with OFC outcome were included. CONCLUSION: We describe a new algorithm with high sensitivity for IgE-mediated food allergy in clinical study participants who do not undergo OFC. CLINICAL RELEVANCE: This may be a useful tool for excluding food allergy in future clinical studies where OFC is not conducted

Effect of methylphenidate treatment during adolescence on norepinephrine transporter function in orbitofrontal cortex in a rat model of attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is associated with hypofunctional medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC). Methylphenidate (MPH) remediates ADHD, in part, by inhibiting the norepinephrine transporter (NET). MPH also reduces ADHD-like symptoms in spontaneously hypertensive rats (SHRs), a model of ADHD. However, effects of chronic MPH treatment on NET function in mPFC and OFC in SHR have not been reported. In the current study, long-term effects of repeated treatment with a therapeutically relevant oral dose of MPH during adolescence on NET function in subregions of mPFC (cingulate gyrus, prelimbic cortex and infralimbic cortex) and in the OFC of adult SHR, Wistar-Kyoto (WKY, inbred control) and Wistar (WIS, outbred control) rats were determined using in vivo voltammetry. Following local ejection of norepinephrine (NE), uptake rate was determined as peak amplitude (Amax)× first-order rate constant (k-1). In mPFC subregions, no strain or treatment effects were found in NE uptake rate. In OFC, NE uptake rate in vehicle-treated adult SHR was greater than in adult WKY and WIS administered vehicle. MPH treatment during adolescence normalized NE uptake rate in OFC in SHR. Thus, the current study implicates increased NET function in OFC as an underlying mechanism for reduced noradrenergic transmission in OFC, and consequently, the behavioral deficits associated with ADHD. MPH treatment during adolescence normalized NET function in OFC in adulthood, suggesting that the therapeutic action of MPH persists long after treatment cessation and may contribute to lasting reductions in deficits associated with ADHD.UL1 TR000117 - NCATS NIH HHS; R01 DA011716 - NIDA NIH HHS; P50 DA005312 - NIDA NIH HHS; P50 DA05312 - NIDA NIH HHS; R01 DA11716 - NIDA NIH HH

Effect of methylphenidate treatment during adolescence on norepinephrine transporter function in orbitofrontal cortex in a rat model of attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is associated with hypofunctional medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC). Methylphenidate (MPH) remediates ADHD, in part, by inhibiting the norepinephrine transporter (NET). MPH also reduces ADHD-like symptoms in spontaneously hypertensive rats (SHRs), a model of ADHD. However, effects of chronic MPH treatment on NET function in mPFC and OFC in SHR have not been reported. In the current study, long-term effects of repeated treatment with a therapeutically relevant oral dose of MPH during adolescence on NET function in subregions of mPFC (cingulate gyrus, prelimbic cortex and infralimbic cortex) and in the OFC of adult SHR, Wistar-Kyoto (WKY, inbred control) and Wistar (WIS, outbred control) rats were determined using in vivo voltammetry. Following local ejection of norepinephrine (NE), uptake rate was determined as peak amplitude (Amax)× first-order rate constant (k-1). In mPFC subregions, no strain or treatment effects were found in NE uptake rate. In OFC, NE uptake rate in vehicle-treated adult SHR was greater than in adult WKY and WIS administered vehicle. MPH treatment during adolescence normalized NE uptake rate in OFC in SHR. Thus, the current study implicates increased NET function in OFC as an underlying mechanism for reduced noradrenergic transmission in OFC, and consequently, the behavioral deficits associated with ADHD. MPH treatment during adolescence normalized NET function in OFC in adulthood, suggesting that the therapeutic action of MPH persists long after treatment cessation and may contribute to lasting reductions in deficits associated with ADHD.UL1 TR000117 - NCATS NIH HHS; R01 DA011716 - NIDA NIH HHS; P50 DA005312 - NIDA NIH HHS; P50 DA05312 - NIDA NIH HHS; R01 DA11716 - NIDA NIH HH

Network of recurrent events for the Olami-Feder-Christensen model

We numerically study the dynamics of a discrete spring-block model introduced by Olami, Feder and Christensen (OFC) to mimic earthquakes and investigate to which extent this simple model is able to reproduce the observed spatiotemporal clustering of seismicty. Following a recently proposed method to characterize such clustering by networks of recurrent events [Geophys. Res. Lett. {\bf 33}, L1304, 2006], we find that for synthetic catalogs generated by the OFC model these networks have many non-trivial statistical properties. This includes characteristic degree distributions -- very similar to what has been observed for real seismicity. There are, however, also significant differences between the OFC model and earthquake catalogs indicating that this simple model is insufficient to account for certain aspects of the spatiotemporal clustering of seismicity.Comment: 11 pages, 16 figure

Factors Impacting Participation In and Purchases Made by Members of the Oklahoma Food Cooperative

The Oklahoma Food Cooperative (OFC) facilitates transactions between producers and consumers of locally-grown food items. Even with more than 3,000 members and roughly $1M in annual sales, the OFC still needs to establish its long-term sustainability. Both customer-members and supplier-members of the OFC were surveyed to determine the factors driving their current and continued participation in the cooperative.cooperative, local food movement, member communications, business sustainability, strategic planning, Agribusiness, Institutional and Behavioral Economics, Marketing,

Noise characterization of an Optical Frequency Comb using Offline Cross-Correlation

Using an offline cross-correlation technique, we have analyzed the noise behavior of a new type of optical frequency comb (OFC), which is carrier envelope offset (CEO) free by configuration, due to difference frequency generation. In order to evaluate the instrument's ultimate noise floor, the phase and amplitude noise of a stabilized OFC are measured simultaneously using two analog-to-digital converters. Carrier recovery and phase detection are done by post-processing, eliminating the need for external phase-locked loops and complex calibration techniques. In order to adapt the measurement noise floor and the number of averages used in cross correlation, an adaptive frequency resolution for noise measurement is applied. Phase noise results are in excellent agreement with measurements of the fluctuations of the repetition frequency of the OFC obtained from optical signal

Rule learning enhances structural plasticity of long-range axons in frontal cortex.

Rules encompass cue-action-outcome associations used to guide decisions and strategies in a specific context. Subregions of the frontal cortex including the orbitofrontal cortex (OFC) and dorsomedial prefrontal cortex (dmPFC) are implicated in rule learning, although changes in structural connectivity underlying rule learning are poorly understood. We imaged OFC axonal projections to dmPFC during training in a multiple choice foraging task and used a reinforcement learning model to quantify explore-exploit strategy use and prediction error magnitude. Here we show that rule training, but not experience of reward alone, enhances OFC bouton plasticity. Baseline bouton density and gains during training correlate with rule exploitation, while bouton loss correlates with exploration and scales with the magnitude of experienced prediction errors. We conclude that rule learning sculpts frontal cortex interconnectivity and adjusts a thermostat for the explore-exploit balance

Offshore Financial Centers: Parasites or Symbionts?

This paper analyzes the causes and consequences of offshore financial centers (OFCs). Since OFCs are likely to be tax havens and money launderers, they encourage bad behavior in source countries. Nevertheless, OFCs may also have unintended positive consequences for their neighbors, since they act as a competitive fringe for the domestic banking sector. We derive and simulate a model of a home country monopoly bank facing a representative competitive OFC which offers tax advantages attained by moving assets offshore at a cost that is increasing in distance between the OFC and the source. Our model predicts that proximity to an OFC is likely to have pro-competitive implications for the domestic banking sector, although the overall effect on welfare is ambiguous. We test and confirm the predictions empirically. OFC proximity is associated with a more competitive domestic banking system and greater overall financial depth.