Multifocal VEP (mfVEP) reveals abnormal neuronal delays in diabetes

This pilot study examined the diagnostic role of multifocal visually evoked potentials (mfVEP) in a small number of patients with diabetes. mfVEP, mfERG, and fundus photographs of both eyes of five patients with diabetes, three with nonproliferative diabetic retinopathy (NPDR) and two without NPDR were examined. Thirteen control subjects were also examined. Eighteen zones were constructed from the 60-element mfVEP stimulus array. mfVEP implicit time (IT) and amplitude (SNR) differences were tested between subject groups. We also examined whether there was a difference in function for patches with and without retinopathy in the NPDR group. Lastly, we compared mfVEP and mfERG results in the same patients. We found significant mfVEP IT differences between controls and all patients with diabetes, controls and diabetics without retinopathy, and between controls and diabetics with retinopathy. The subject groups did not differ significantly in terms of SNR. In the retinopathy group, ITs from zones with retinopathy were significantly longer than ITs from zones without retinopathy (P = 0.016). mfERG IT was more frequently abnormal than mfVEP IT. In addition, mfERG hexagons were twice as likely to be abnormal if the corresponding mfVEP zone was abnormal (P < 0.05). mfVEP implicit times are significantly delayed in patients with diabetes even when there is no retinopathy. These cortical response results are similar, albeit considerably less abnormal, than those previously reported for retinal (mfERG) responses in patients with diabetes. A correlation exists between the location of abnormal mfERG hexagons and abnormal mfVEP zones

Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch

Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occuring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms. Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale.Comment: 14 pages, 4 figure

Characterization of Synaptically Connected Nuclei in a Potential Sensorimotor Feedback Pathway in the Zebra Finch Song System

Birdsong is a learned behavior that is controlled by a group of identified nuclei, known collectively as the song system. The cortical nucleus HVC (used as a proper name) is a focal point of many investigations as it is necessary for song production, song learning, and receives selective auditory information. HVC receives input from several sources including the cortical area MMAN (medial magnocellular nucleus of the nidopallium). The MMAN to HVC connection is particularly interesting as it provides potential sensorimotor feedback to HVC. To begin to understand the role of this connection, we investigated the physiological relation between MMAN and HVC activity with simultaneous multiunit extracellular recordings from these two nuclei in urethane anesthetized zebra finches. As previously reported, we found similar timing in spontaneous bursts of activity in MMAN and HVC. Like HVC, MMAN responds to auditory playback of the bird's own song (BOS), but had little response to reversed BOS or conspecific song. Stimulation of MMAN resulted in evoked activity in HVC, indicating functional excitation from MMAN to HVC. However, inactivation of MMAN resulted in no consistent change in auditory responses in HVC. Taken together, these results indicate that MMAN provides functional excitatory input to HVC but does not provide significant auditory input to HVC in anesthetized animals. We hypothesize that MMAN may play a role in motor reinforcement or coordination, or may provide modulatory input to the song system about the internal state of the animal as it receives input from the hypothalamus

Unhealthy Gambling Amongst New Zealand Secondary School Students: An Exploration of Risk and Protective Factors

This study sought to determine the prevalence of gambling and unhealthy gambling behaviour and describe risk and protective factors associated with these behaviours amongst a nationally representative sample of New Zealand secondary school students (n = 8,500). Factor analysis and item response theory were used to develop a model to provide a measure of ‘unhealthy gambling’. Logistic regressions and multiple logistic regression models were used to investigate associations between unhealthy gambling behaviour and selected outcomes. Approximately one-quarter (24.2 %) of students had gambled in the last year, and 4.8 % had two or more indicators of unhealthy gambling. Multivariate analyses found that unhealthy gambling was associated with four main factors: more accepting attitudes towards gambling (pp = 0.0061); being worried about and/or trying to cut down on gambling (p p = 0.0009). Unhealthy gambling is a significant health issue for young people in New Zealand. Ethnic and social inequalities were apparent and these disparities need to be addressed

Functional MRI of Auditory Responses in the Zebra Finch Forebrain Reveals a Hierarchical Organisation Based on Signal Strength but Not Selectivity

BACKGROUND: Male songbirds learn their songs from an adult tutor when they are young. A network of brain nuclei known as the 'song system' is the likely neural substrate for sensorimotor learning and production of song, but the neural networks involved in processing the auditory feedback signals necessary for song learning and maintenance remain unknown. Determining which regions show preferential responsiveness to the bird's own song (BOS) is of great importance because neurons sensitive to self-generated vocalisations could mediate this auditory feedback process. Neurons in the song nuclei and in a secondary auditory area, the caudal medial mesopallium (CMM), show selective responses to the BOS. The aim of the present study is to investigate the emergence of BOS selectivity within the network of primary auditory sub-regions in the avian pallium. METHODS AND FINDINGS: Using blood oxygen level-dependent (BOLD) fMRI, we investigated neural responsiveness to natural and manipulated self-generated vocalisations and compared the selectivity for BOS and conspecific song in different sub-regions of the thalamo-recipient area Field L. Zebra finch males were exposed to conspecific song, BOS and to synthetic variations on BOS that differed in spectro-temporal and/or modulation phase structure. We found significant differences in the strength of BOLD responses between regions L2a, L2b and CMM, but no inter-stimuli differences within regions. In particular, we have shown that the overall signal strength to song and synthetic variations thereof was different within two sub-regions of Field L2: zone L2a was significantly more activated compared to the adjacent sub-region L2b. CONCLUSIONS: Based on our results we suggest that unlike nuclei in the song system, sub-regions in the primary auditory pallium do not show selectivity for the BOS, but appear to show different levels of activity with exposure to any sound according to their place in the auditory processing stream

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Global flash multifocal electroretinogram: early detection of local functional changes and its correlations with optical coherence tomography and visual field tests in diabetic eyes

Purpose: To investigate the correlations of the global flash multifocal electroretinogram (MOFO mfERG) with common clinical visual assessments – Humphrey perimetry and Stratus circumpapillary retinal nerve fiber layer (RNFL) thickness measurement in type II diabetic patients. Methods: Forty-two diabetic patients participated in the study: ten were free from diabetic retinopathy (DR) while the remainder suffered from mild to moderate non-proliferative diabetic retinopathy (NPDR). Fourteen age-matched controls were recruited for comparison. MOFO mfERG measurements were made under high and low contrast conditions. Humphrey central 30-2 perimetry and Stratus OCT circumpapillary RNFL thickness measurements were also performed. Correlations between local values of implicit time and amplitude of the mfERG components (direct component (DC) and induced component (IC)), and perimetric sensitivity and RNFL thickness were evaluated by mapping the localized responses for the three subject groups. Results: MOFO mfERG was superior to perimetry and RNFL assessments in showing differences between the diabetic groups (with and without DR) and the controls. All the MOFO mfERG amplitudes (except IC amplitude at high contrast) correlated better with perimetry findings (Pearson’s r ranged from 0.23 to 0.36, p<0.01) than did the mfERG implicit time at both high and low contrasts across all subject groups. No consistent correlation was found between the mfERG and RNFL assessments for any group or contrast conditions. The responses of the local MOFO mfERG correlated with local perimetric sensitivity but not with RNFL thickness. Conclusion: Early functional changes in the diabetic retina seem to occur before morphological changes in the RNFL

Linder Revisited: Trade and Development in the Spanish Economy

The literature has tended to treat Linder's hypothesis with excessive simplicity given the absence of any formalization for this intuitive theory on trade potential in manufacturers, closely related to the intra-industry trade paradigm. Against this background, in this paper we first propose a complete empirical model of bilateral trade containing all the determinants suggested by Linder, with special emphasis being placed on non-homothetic preferences, national income distribution, international economic convergence and geographic distance. We then test the model in an appropriate case, namely that of Spain during the period of its economic transition running from approximately 1959 to 1986. This period was characterized by increasing openness and structural change, as well as by convergence until that country's integration into the then European Economic Community. The results confirm the importance of the characteristics of internal demand, essentially of income distribution and non-homothetic preferences. We find that trade horizons delimited by bilateral proximity in development and geographical distance, together with multilateral convergence in economic development are the main indicators for selecting trade partners as markets and suppliers, thereby reinforcing the idea that foreign markets can be considered as an extension of the national market.Economic development, international trade, demand, economic convergence,