Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
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Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Σάββατο, 26 Μαΐου 2018

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Publication date: 1 August 2018
Source:NeuroImage, Volume 176





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Likelihood estimation of drug occupancy for brain PET studies

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Martin Schain, Francesca Zanderigo, R. Todd Ogden
Neuroimaging with PET is unique in its capability to measure in vivo the occupancy of a drug. The occupancy is typically obtained by conducting PET measurements before and after administration of the drug. For radioligands for which no reference region exists, however, the only established procedure to estimate the occupancy from these data is via linear regression analysis, forming the basis for the so-called Lassen plot. There are several reasons why simple linear regression analysis is not ideal for analyzing these data, including regression attenuation and correlated errors.Here, we propose the use of Likelihood Estimation of Occupancy (LEO) in such a situation. Similar to the Lassen plot, LEO uses the total distribution volume estimates at baseline and at block condition as input, but estimates the non-displaceable distribution volume (VND) and fractional occupancy (Δ) via direct maximum likelihood estimation (MLE).This study outlines the rationale for using MLE to estimate Δ and VND from PET data, and evaluates its performance in relation to the Lassen Plot via two separate simulation experiments. Finally, LEO and Lassen plot are applied to a PET dataset acquired with [11C]WAY-100635.LEO can exploit the covariance structure of the data to improve the accuracy and precision of the estimates of Δ and VND. Theoretically, the covariance matrix can be extracted from a test-retest dataset for the radioligand at hand. Several procedures to estimate the covariance matrix were considered as part of the simulation experiments, and the effect of the test-retest sample size was also assessed.The results are conclusive in that MLE can be used to estimate Δ and VND from PET data, avoiding the limitations associated with linear regression. The performance of LEO was, naturally, dependent on the procedure used to estimate the covariance matrix, and the test-retest sample size. Given a test-retest sample size of at least 5, but preferably 10 individuals, LEO provides higher accuracy and precision than Lassen plot in the estimation of Δ and VND. We conclude that LEO is valuable in drug occupancy studies.



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Is the encoding of Reward Prediction Error reliable during development?

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Hanna Keren, Gang Chen, Brenda Benson, Monique Ernst, Ellen Leibenluft, Nathan A. Fox, Daniel S. Pine, Argyris Stringaris
Reward Prediction Errors (RPEs), defined as the difference between the expected and received outcomes, are integral to reinforcement learning models and play an important role in development and psychopathology. In humans, RPE encoding can be estimated using fMRI recordings, however, a basic measurement property of RPE signals, their test-retest reliability across different time scales, remains an open question. In this paper, we examine the 3-month and 3-year reliability of RPE encoding in youth (mean age at baseline = 10.6 ± 0.3 years), a period of developmental transitions in reward processing. We show that RPE encoding is differentially distributed between the positive values being encoded predominantly in the striatum and negative RPEs primarily encoded in the insula. The encoding of negative RPE values is highly reliable in the right insula, across both the long and the short time intervals. Insula reliability for RPE encoding is the most robust finding, while other regions, such as the striatum, are less consistent. Striatal reliability appeared significant as well once covarying for factors, which were possibly confounding the signal to noise ratio. By contrast, task activation during feedback in the striatum is highly reliable across both time intervals. These results demonstrate the valence-dependent differential encoding of RPE signals between the insula and striatum, and the consistency of RPE signals or lack thereof, during childhood and into adolescence. Characterizing the regions where the RPE signal in BOLD fMRI is a reliable marker is key for estimating reward-processing alterations in longitudinal designs, such as developmental or treatment studies.



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Extreme weather event may induce Microcystis blooms in the Qiantang River, Southeast China

Abstract

A severe cyanobacterial bloom in the mainstem of a large Chinese river was first reported from China. The Qiantang River is the longest river in the Zhejiang province, southeast China. It provides drinking water supply to ~ 16 million people, including Hangzhou city. Fifteen sites along the Qiantang River (including upper, middle (Fuchunjiang Reservoir), and lower reaches and tributaries) were sampled between August 13 and September 9, 2016 to conduct a preliminary examination of the outbreak of Microcystis blooms. Laboratory investigation revealed that Microcystis spp. are dominant in the Fuchunjiang Reservoir (an overflow reservoir on the mainstem of the Qiantang River) with an extremely high cell density of 2.3 × 108 cells/L, leading to a severe bloom in the mainstem of the Qiantang River. Investigations of the meteorological, hydrological, and nutrient characteristics associated with the bloom indicated that extremely dry (6.8 mm rainfall from August 13 to September 9, 2016) and hot (32 consecutive days of temperatures > 30 °C from July 20 to August 31, 2016) weather might be the key factors triggering the bloom. Additionally, the extremely low flow of the tributary, Lanjiang River (142 ± 56 m3/s from August 13 to September 9), and its high nutrient background, favored the bloom. While nutrient reductions are important, the most immediate and effective management approach might be to implement appropriate minimal flow conditions to mitigate the blooms.



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Circulating integrin alpha4/beta7+ lymphocytes targeted by vedolizumab have a pro-inflammatory phenotype

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Publication date: Available online 26 May 2018
Source:Clinical Immunology
Author(s): James D. Lord, S. Alice Long, Donna M. Shows, Jerill Thorpe, Katherine Schwedhelm, Janice Chen, Mariko Kita, Jane H. Buckner
Integrin alpha4/beta7 on circulating lymphocytes identifies them as gut-tropic, and can be targeted by the humanized antibody vedolizumab to treat inflammatory bowel disease (IBD). We found lymphocytes expressing alpha4/beta7 were significantly more responsive to the pro-inflammatory cytokines IL-6, IL-7, and IL-21, and less responsive to the regulatory T cell (Treg)-supporting cytokine IL-2. Alpha4/beta7 was expressed by a smaller percent of FOXP3 + Helios+ thymically-derived Tregs (tTregs) than FOXP3 + Helios- peripherally-derived Tregs (pTregs) or FOXP3- effector T cells. Integrin alpha4/beta7+ CD4 T cells were also rare among cells expressing the Th2 marker CRTh2, but enriched in cells bearing the circulating T follicular helper cell marker CXCR5. Thus the effect of this anti-integrin therapy on the mucosal immune system may be more qualitative than quantitative, and selectively replace pro-inflammatory effector cells with Tregs and Th2 cells to facilitate immune tolerance in the mucosa without globally depleting lymphocytes from the intestinal mucosa.



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Combination of anti-citrullinated protein antibodies and rheumatoid factor is associated with increased systemic inflammatory mediators and more rapid progression from preclinical to clinical rheumatoid arthritis

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Publication date: Available online 26 May 2018
Source:Clinical Immunology
Author(s): Nithya Lingampalli, Jeremy Sokolove, Lauren J. Lahey, Jess D. Edison, William R. Gilliland, V. Michael Holers, Kevin D. Deane, William H. Robinson
The development of rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPAs) can be observed years prior to clinical diagnosis of rheumatoid arthritis (RA). Nevertheless, the interaction between these two autoantibodies and their combined effect on development of RA is unclear. We measured RF, cytokines, and ACPA subtypes in serial pre-clinical serum samples collected from 83 US veterans who all developed RA. Levels of cytokines and ACPAs were compared between the following groups: anti-cyclic citrullinated peptide (anti-CCP)-/RF- (double negative), anti-CCP+/RF-, anti-CCP-/RF+, or anti-CCP+/RF+ (double-positive). The double-positive subgroup had significantly higher levels of 20 inflammatory cytokines and 29 ACPA reactivities, and the shortest interval, 1.3 years, between the preclinical sample timepoint and diagnosis of RA. Thus, the combined presence of ACPAs and RF is associated with a more rapid progression to RA, suggesting that anti-CCP+/RF+ individuals have a more advanced preclinical disease state and that the onset of RA may be imminent.



https://ift.tt/2GQNYCB

Circulating integrin alpha4/beta7+ lymphocytes targeted by vedolizumab have a pro-inflammatory phenotype

S15216616.gif

Publication date: Available online 26 May 2018
Source:Clinical Immunology
Author(s): James D. Lord, S. Alice Long, Donna M. Shows, Jerill Thorpe, Katherine Schwedhelm, Janice Chen, Mariko Kita, Jane H. Buckner
Integrin alpha4/beta7 on circulating lymphocytes identifies them as gut-tropic, and can be targeted by the humanized antibody vedolizumab to treat inflammatory bowel disease (IBD). We found lymphocytes expressing alpha4/beta7 were significantly more responsive to the pro-inflammatory cytokines IL-6, IL-7, and IL-21, and less responsive to the regulatory T cell (Treg)-supporting cytokine IL-2. Alpha4/beta7 was expressed by a smaller percent of FOXP3 + Helios+ thymically-derived Tregs (tTregs) than FOXP3 + Helios- peripherally-derived Tregs (pTregs) or FOXP3- effector T cells. Integrin alpha4/beta7+ CD4 T cells were also rare among cells expressing the Th2 marker CRTh2, but enriched in cells bearing the circulating T follicular helper cell marker CXCR5. Thus the effect of this anti-integrin therapy on the mucosal immune system may be more qualitative than quantitative, and selectively replace pro-inflammatory effector cells with Tregs and Th2 cells to facilitate immune tolerance in the mucosa without globally depleting lymphocytes from the intestinal mucosa.



https://ift.tt/2IQ6BfG