Redistribution of Synaptic Efficacy Supports Stable Pattern Learning in Neural Networks

Markram and Tsodyks, by showing that the elevated synaptic efficacy observed with single-pulse LTP measurements disappears with higher-frequency test pulses, have critically challenged the conventional assumption that LTP reflects a general gain increase. Redistribution of synaptic efficacy (RSE) is here seen as the local realization of a global design principle in a neural network for pattern coding. As is typical of many coding systems, the network learns by dynamically balancing a pattern-independent increase in strength against a pattern-specific increase in selectivity. This computation is implemented by a monotonic long-term memory process which has a bidirectional effect on the postsynaptic potential via functionally complementary signal components. These frequency-dependent and frequency-independent components realize the balance between specific and nonspecific functions at each synapse. This synaptic balance suggests a functional purpose for RSE which, by dynamically bounding total memory change, implements a distributed coding scheme which is stable with fast as well as slow learning. Although RSE would seem to make it impossible to code high-frequency input features, a network preprocessing step called complement coding symmetrizes the input representation, which allows the system to encode high-frequency as well as low-frequency features in an input pattern. A possible physical model interprets the two synaptic signal components in terms of ligand-gated and voltage-gated receptors, where learning converts channels from one type to another.Office of Naval Research and the Defense Advanced Research Projects Agency (N00014-95-1-0409, N00014-1-95-0657

Distributed ARTMAP

Distributed coding at the hidden layer of a multi-layer perceptron (MLP) endows the network with memory compression and noise tolerance capabilities. However, an MLP typically requires slow off-line learning to avoid catastrophic forgetting in an open input environment. An adaptive resonance theory (ART) model is designed to guarantee stable memories even with fast on-line learning. However, ART stability typically requires winner-take-all coding, which may cause category proliferation in a noisy input environment. Distributed ARTMAP (dARTMAP) seeks to combine the computational advantages of MLP and ART systems in a real-time neural network for supervised learning. This system incorporates elements of the unsupervised dART model as well as new features, including a content-addressable memory (CAM) rule. Simulations show that dARTMAP retains fuzzy ARTMAP accuracy while significantly improving memory compression. The model's computational learning rules correspond to paradoxical cortical data.Office of Naval Research (N00014-95-1-0409, N00014-95-1-0657

dARTMAP: A Neural Network for Fast Distributed Supervised Learning

Distributed coding at the hidden layer of a multi-layer perceptron (MLP) endows the network with memory compression and noise tolerance capabilities. However, an MLP typically requires slow off-line learning to avoid catastrophic forgetting in an open input environment. An adaptive resonance theory (ART) model is designed to guarantee stable memories even with fast on-line learning. However, ART stability typically requires winner-take-all coding, which may cause category proliferation in a noisy input environment. Distributed ARTMAP (dARTMAP) seeks to combine the computational advantages of MLP and ART systems in a real-time neural network for supervised learning, An implementation algorithm here describes one class of dARTMAP networks. This system incorporates elements of the unsupervised dART model as well as new features, including a content-addressable memory (CAM) rule for improved contrast control at the coding field. A dARTMAP system reduces to fuzzy ARTMAP when coding is winner-take-all. Simulations show that dARTMAP retains fuzzy ARTMAP accuracy while significantly improving memory compression.National Science Foundation (IRI-94-01659); Office of Naval Research (N00014-95-1-0409, N00014-95-0657

La mujer saudí, la mujer prohibida. Representaciones y realidades en publicidad y cine

Arabia Saudita es uno de los países mas extremos del mundo, en el que la represión femenina se ha convertido en una parte inseparable de la política del gobierno. Debido a que se trata de una país introvertido y conservador, existen muy pocos análisis sobre el papel que ocupa la mujer en la sociedad saudita. Las pocas veces que aparece reflejada en el espacio público es mediante publicaciones en presnsa, relacionadas y enfocadas hacia un ema en cocreto. En este contexto, el ofjetivo de este proyecto de investigación es realizar un estudio más profundo sobre la vida femenina, es decir, dar a conocer a la mujer saudí a través tanto de la industria cinematográfica como del ámbito publicitario.Grado en Publicidad y Relaciones Pública

Photocatalytic UV-Induced Approach for Discoloration of Bromocresol Purple, Bromothymol Blue Dyes and Their Mixture Using Nix Fe3−xO4/Fe2O3/AC Composites

The nickel ferrite-activated carbon samples NiFe2O4/Activated carbon and NixFe3−xO4/Fe2O3/AC, x = 0.25; 0.5 obtained by co-precipitation followed by thermal treatment in inert atmosphere, were studied for discoloration of Bromocresol Purple (BCP), Bromothymol Blue (BTB) dyes and their mixture as model contaminants under UV-A light. The prepared materials were investigated by XPS, PXRD and XRF analysis, FT-IR spectroscopy, SEM, EDX, BET method and TG analysis. The photocatalyst with composition NixFe3−xO4-AC, x = 1 has demonstrated the highest photocatalytic activity towards discoloration of the BTB in comparison with the others tested materials NixFe3−xO4/Fe2O3/AC, x = 0.25; 0.5. These results can be explained with the smaller particle sizes, the mesoporous structure, the higher degree of crystallinity and higher content of hydroxyl groups. This study proved that the obtained nickel ferrite-activated carbon materials are suitable as photocatalysts for discoloration of the BTB dye. They have demonstrated also relatively high adsorption ability towards BCP dye

The development of the concept of return-on-investment from large-scale quality improvement programmes in healthcare: an integrative systematic literature review

BACKGROUND: Return on Investment (ROI) is increasingly being used to evaluate financial benefits from healthcare Quality Improvement (QI). ROI is traditionally used to evaluate investment performance in the commercial field. Little is known about ROI in healthcare. The aim of this systematic review was to analyse and develop ROI as a concept and develop a ROI conceptual framework for large-scale healthcare QI programmes. METHODS: We searched Medline, Embase, Global health, PsycInfo, EconLit, NHS EED, Web of Science, Google Scholar using ROI or returns-on-investment concepts (e.g., cost–benefit, cost-effectiveness, value). We combined this terms with healthcare and QI. Included articles discussed at least three organisational QI benefits, including financial or patient benefits. We synthesised the different ways in which ROI or return-on-investment concepts were used and discussed by the QI literature; first the economically focused, then the non-economically focused QI literature. We then integrated these literatures to summarise their combined views. RESULTS: We retrieved 10 428 articles. One hundred and two (102) articles were selected for full text screening. Of these 34 were excluded and 68 included. The included articles were QI economic, effectiveness, process, and impact evaluations as well as reports and conceptual literature. Fifteen of 68 articles were directly focused on QI programme economic outcomes. Of these, only four focused on ROI. ROI related concepts in this group included cost-effectiveness, cost–benefit, ROI, cost-saving, cost-reduction, and cost-avoidance. The remaining articles mainly mentioned efficiency, productivity, value, or benefits. Financial outcomes were not the main goal of QI programmes. We found that the ROI concept in healthcare QI aligned with the concepts of value and benefit, both monetary and non-monetary. CONCLUSION: Our analysis of the reviewed literature indicates that ROI in QI is conceptualised as value or benefit as demonstrated through a combination of significant outcomes for one or more stakeholders in healthcare organisations. As such, organisations at different developmental stages can deduce benefits that are relevant and legitimate as per their contextual needs. TRIAL REGISTRATION: Review registration: PROSPERO; CRD42021236948. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-022-08832-3

Key lessons learned from the INDIGO global network on mental health related stigma and discrimination

No description supplie

Oncolytic Adenovirus ORCA-010 Activates Proinflammatory Myeloid Cells and Facilitates T Cell Recruitment and Activation by PD-1 Blockade in Melanoma

Immune checkpoint inhibitors have advanced the treatment of melanoma. Nevertheless, a majority of patients are resistant, or develop resistance, to immune checkpoint blockade, which may be related to prevailing immune suppression by myeloid regulatory cells in the tumor microenvironment (TME). ORCA-010 is a novel oncolytic adenovirus that selectively replicates in, and lyses, cancer cells. We previously showed that ORCA-010 can activate melanoma-exposed conventional dendritic cells (cDCs). To study the effect of ORCA-010 on melanoma-conditioned macrophage development, we used an in vitro co-culture model of human monocytes with melanoma cell lines. We observed a selective survival and polarization of monocytes into M2-like macrophages (CD14(+)CD80(-)CD163(+)) in co-cultures with cell lines that expressed macrophage colony-stimulating factor. Oncolysis of these melanoma cell lines, effected by ORCA-010, activated the resulting macrophages and converted them to a more proinflammatory state, evidenced by higher levels of PD-L1, CD80, and CD86 and an enhanced capacity to prime allogenic T cells and induce a type-1 T cell response. To assess the effect of ORCA-010 on myeloid subset distribution and activation in vivo, ORCA-010 was intratumorally injected and tested for T cell activation and recruitment in the human adenovirus nonpermissive B16-OVA mouse melanoma model. While systemic PD-1 blockade in this model in itself did not modulate myeloid or T cell subset distribution and activation, when it was preceded by i.t. injection of ORCA-010, this induced an increased rate and activation state of CD8 alpha(+) cDC1, both in the TME and in the spleen. Observed increased rates of activated CD8(+) T cells, expressing CD69 and PD-1, were related to both increased CD8 alpha(+) cDC1 rates and M1/M2 shifts in tumor and spleen. In conclusion, the myeloid modulatory properties of ORCA-010 in melanoma, resulting in recruitment and activation of T cells, could enhance the antitumor efficacy of PD-1 blockade.Peer reviewe

Adenovirus Armed With TNFa and IL2 Added to aPD-1 Regimen Mediates Antitumor Efficacy in Tumors Refractory to aPD-1

Immune checkpoint inhibitors such as anti-PD-1 have revolutionized the field of oncology over the past decade. Nevertheless, the majority of patients do not benefit from them. Virotherapy is a flexible tool that can be used to stimulate and/or recruit different immune populations. T-cell enabling virotherapy could enhance the efficacy of immune checkpoint inhibitors, even in tumors resistant to these inhibitors. The T-cell potentiating virotherapy used here consisted of adenoviruses engineered to express tumor necrosis factor alpha and interleukin-2 in the tumor microenvironment. To study virus efficacy in checkpoint-inhibitor resistant tumors, we developed an anti-PD-1 resistant melanoma model in vivo. In resistant tumors, adding virotherapy to an anti-PD-1 regimen resulted in increased survival (p=0.0009), when compared to anti-PD-1 monotherapy. Some of the animals receiving virotherapy displayed complete responses, which did not occur in the immune checkpoint-inhibitor monotherapy group. When adenoviruses were delivered into resistant tumors, there were signs of increased CD8 T-cell infiltration and activation, which - together with a reduced presence of M2 macrophages and myeloid-derived suppressor cells - could explain those results. T-cell enabling virotherapy appeared as a valuable tool to counter resistance to immune checkpoint inhibitors. The clinical translation of this approach could increase the number of cancer patients benefiting from immunotherapies.Peer reviewe