Synchronization in a network of model neurons

We study the spatiotemporal dynamics of a network of coupled chaotic maps modelling neuronal activity, under variation of coupling strength ε and degree of randomness in coupling p. We find that at high coupling strengths (ε > εfixed) the unstable saddle point solution of the local chaotic maps gets stabilized. The range of coupling where this spatiotemporal fixed point gains stability is unchanged in the presence of randomness in the connections, namely εfixed is invariant under changes in p. As coupling gets weaker (ε < εfixed), the spatiotemporal fixed point loses stability, and one obtains chaos. In this regime, when the coupling connections are completely regular (p=0), the network becomes spatiotemporally chaotic. Interestingly however, in the presence of random links (p > 0) one obtains spatial synchronization in the network. We find that this range of synchronized chaos increases exponentially with the fraction of random links in the network. Further, in the space of fixed coupling strengths, the synchronization transition occurs at a finite value of p, a scenario quite distinct from the many examples of synchronization transitions at p→0. Further we show that the synchronization here is robust in the presence of parametric noise, namely in a network of nonidentical neuronal maps. Finally we check the generality of our observations in networks of neurons displaying both spiking and bursting dynamics

Targeted AAV5-Smad7 Gene Therapy Inhibits Corneal Scarring \u3cem\u3ein vivo\u3c/em\u3e

Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring. Hence, therapeutic targets that reduce transdifferentiation of fibroblasts into myofibroblasts may provide a clinically relevant approach to treat corneal fibrosis and improve long-term visual outcomes. Smad7 protein regulates the functional effects of TGFβ signaling during corneal wound healing. We tested that targeted delivery of Smad7 using recombinant adeno-associated virus serotype 5 (AAV5-Smad7) delivered to the corneal stroma can inhibit corneal haze post photorefractive keratectomy (PRK) in vivo in a rabbit corneal injury model. We demonstrate that a single topical application of AAV5-Smad7 in rabbit cornea post-PRK led to a significant decrease in corneal haze and corneal fibrosis. Further, histopathology revealed lack of immune cell infiltration following AAV5-Smad7 gene transfer into the corneal stroma. Our data demonstrates that AAV5-Smad7 gene therapy is relatively safe with significant potential for the treatment of corneal disease currently resulting in fibrosis and impaired vision

Cost-minimization model of a multidisciplinary Antibiotic Stewardship Team based on a successful implementation on a urology ward of an academic hospital

BackgroundIn order to stimulate appropriate antimicrobial use and thereby lower the chances of resistance development, an Antibiotic Stewardship Team (A-Team) has been implemented at the University Medical Center Groningen, the Netherlands. Focus of the A-Team was a pro-active day 2 case-audit, which was financially evaluated here to calculate the return on investment from a hospital perspective.MethodsEffects were evaluated by comparing audited patients with a historic cohort with the same diagnosis-related groups. Based upon this evaluation a cost-minimization model was created that can be used to predict the financial effects of a day 2 case-audit. Sensitivity analyses were performed to deal with uncertainties. Finally, the model was used to financially evaluate the A-Team.ResultsOne whole year including 114 patients was evaluated. Implementation costs were calculated to be (sic)17,732, which represent total costs spent to implement this A-Team. For this specific patient group admitted to a urology ward and consulted on day 2 by the A-Team, the model estimated total savings of (sic)60,306 after one year for this single department, leading to a return on investment of 5.9.ConclusionsThe implemented multi-disciplinary A-Team performing a day 2 case-audit in the hospital had a positive return on investment caused by a reduced length of stay due to a more appropriate antibiotic therapy. Based on the extensive data analysis, a model of this intervention could be constructed. This model could be used by other institutions, using their own data to estimate the effects of a day 2 case-audit in their hospital.</p

An integrated stewardship model: antimicrobial, infection prevention and diagnostic (AID)

Considering the threat of antimicrobial resistance and the difficulties it entails in treating infections, it is necessary to cross borders and approach infection management in an integrated, multidisciplinary manner. We propose the antimicrobial, infection prevention and diagnostic stewardship model comprising three intertwined programs: antimicrobial, infection prevention and diagnostic stewardship, involving all stakeholders. The focus is a so-called ‘theragnostics’ approach. This leads to a personalized infection management plan, improving patient care and minimizing resistance development. Furthermore, it is important that healthcare regions nationally and internationally work together, ensuring that the patient (and microorganism) transfers will not cause problems in a neighboring institution. This antimicrobial, infection prevention and diagnostic stewardship model can serve as a blue print to implement innovative, integrative infection management

Targeted AAV5-Smad7 gene therapy inhibits corneal scarring in vivo.

Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring. Hence, therapeutic targets that reduce transdifferentiation of fibroblasts into myofibroblasts may provide a clinically relevant approach to treat corneal fibrosis and improve long-term visual outcomes. Smad7 protein regulates the functional effects of TGFβ signaling during corneal wound healing. We tested that targeted delivery of Smad7 using recombinant adeno-associated virus serotype 5 (AAV5-Smad7) delivered to the corneal stroma can inhibit corneal haze post photorefractive keratectomy (PRK) in vivo in a rabbit corneal injury model. We demonstrate that a single topical application of AAV5-Smad7 in rabbit cornea post-PRK led to a significant decrease in corneal haze and corneal fibrosis. Further, histopathology revealed lack of immune cell infiltration following AAV5-Smad7 gene transfer into the corneal stroma. Our data demonstrates that AAV5-Smad7 gene therapy is relatively safe with significant potential for the treatment of corneal disease currently resulting in fibrosis and impaired vision

Coupled Maps on Trees

We study coupled maps on a Cayley tree, with local (nearest-neighbor) interactions, and with a variety of boundary conditions. The homogeneous state (where every lattice site has the same value) and the node-synchronized state (where sites of a given generation have the same value) are both shown to occur for particular values of the parameters and coupling constants. We study the stability of these states and their domains of attraction. As the number of sites that become synchronized is much higher compared to that on a regular lattice, control is easier to effect. A general procedure is given to deduce the eigenvalue spectrum for these states. Perturbations of the synchronized state lead to different spatio-temporal structures. We find that a mean-field like treatment is valid on this (effectively infinite dimensional) lattice.Comment: latex file (25 pages), 4 figures included. To be published in Phys. Rev.

Novel Combination BMP7 and HGF Gene Therapy Instigates Selective Myofibroblast Apoptosis and Reduces Corneal Haze In Vivo.

PurposeWe tested the potential of bone morphogenic protein 7 (BMP7) and hepatocyte growth factor (HGF) combination gene therapy to treat preformed corneal fibrosis using established rabbit in vivo and human in vitro models.MethodsEighteen New Zealand White rabbits were used. Corneal fibrosis was produced by alkali injury. Twenty-four hours after scar formation, cornea received topically either balanced salt solution (BSS; n = 6), polyethylenimine-conjugated gold nanoparticle (PEI2-GNP)-naked plasmid (n = 6) or PEI2-GNP plasmids expressing BMP7 and HGF genes (n = 6). Donor human corneas were used to obtain primary human corneal fibroblasts and myofibroblasts for mechanistic studies. Gene therapy effects on corneal fibrosis and ocular safety were evaluated by slit-lamp microscope, stereo microscopes, quantitative real-time PCR, immunofluorescence, TUNEL, modified MacDonald-Shadduck scoring system, and Draize tests.ResultsPEI2-GNP-mediated BMP7+HGF gene therapy significantly decreased corneal fibrosis in live rabbits in vivo (Fantes scale was 0.6 in BMP7+HGF-treated eyes compared to 3.3 in -therapy group; P 104 gene copies per microgram DNA of BMP7 and HGF genes. The recombinant HGF rendered apoptosis in corneal myofibroblasts but not in fibroblasts. Localized topical BMP7+HGF therapy showed no ocular toxicity.ConclusionsLocalized topical BMP7+HGF gene therapy treats corneal fibrosis and restores transparency in vivo mitigating excessive healing and rendering selective apoptosis in myofibroblasts

Genetic Ancestry, Self-Reported Race and Ethnicity in African Americans and European Americans in the PCaP Cohort

Family history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP.Individual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states.Mean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered "no" to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA.Mean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity. Accurately accounting for genetic admixture in this cohort is essential for future analyses of the genetic and environmental contributions to CaP

A synergistic ozone-climate control to address emerging ozone pollution challenges

Tropospheric ozone threatens human health and crop yields, exacerbates global warming, and fundamentally changes atmospheric chemistry. Evidence has pointed toward widespread ozone increases in the troposphere, and particularly surface ozone is chemically complex and difficult to abate. Despite past successes in some regions, a solution to new challenges of ozone pollution in a warming climate remains unexplored. In this perspective, by compiling surface measurements at ∼4,300 sites worldwide between 2014 and 2019, we show the emerging global challenge of ozone pollution, featuring the unintentional rise in ozone due to the uncoordinated emissions reduction and increasing climate penalty. On the basis of shared emission sources, interactive chemical mechanisms, and synergistic health effects between ozone pollution and climate warming, we propose a synergistic ozone-climate control strategy incorporating joint control of ozone and fine particulate matter. This new solution presents an opportunity to alleviate tropospheric ozone pollution in the forthcoming low-carbon transition.This study was supported by the Research Grants Council of Hong Kong Special Administrative Region via General Research Funds (HKBU 15219621 and PolyU 15212421) and a Theme-based Research Scheme (T24-504/17-N). The authors acknowledge the support of the Australia–China Centre on Air Quality Science and Management. R.S. acknowledges support from ANID/FONDAP/1522A0001. D.S. thanks the program of Coordination for the Improvement of Higher Education Personnel (CAPES) (436466/2018-0). X.X. acknowledges funding from the Natural Science Foundation of China (41330422) and the Chinese Academy of Meteorological Sciences (2020KJ003). K.L. is supported by the Natural Science Foundation of China (42205114), Jiangsu Carbon Peak and Neutrality Science and Technology Innovation fund (BK20220031), and the Startup Foundation for Introducing Talent of NUIST. We sincerely appreciate all the organizations and programs introduced in the section “experimental procedures” for freely providing ozone data. We thank Dr. Owen Cooper (University of Colorado, Boulder, and NOAA) for insightful guidance and discussion. No organization or program will be responsible for the results generated from their data.Peer reviewe