Excitatory versus inhibitory feedback in Bayesian formulations of scene construction

The selective attention for identification model (SAIM) is an established model of selective visual attention. SAIM implements translation-invariant object recognition, in scenes with multiple objects, using the parallel distributed processing (PDP) paradigm. Here, we show that SAIM can be formulated as Bayesian inference. Crucially, SAIM uses excitatory feedback to combine top-down information (i.e. object knowledge) with bottom-up sensory information. By contrast, predictive coding implementations of Bayesian inference use inhibitory feedback. By formulating SAIM as a predictive coding scheme, we created a new version of SAIM that uses inhibitory feedback. Simulation studies showed that both types of architectures can reproduce the response time costs induced by multiple objects—as found in visual search experiments. However, due to the different nature of the feedback, the two SAIM schemes make distinct predictions about the motifs of microcircuits mediating the effects of top-down afferents. We discuss empirical (neuroimaging) methods to test the predictions of the two inference architectures

No excess of mitochondrial DNA deletions within muscle in progressive multiple sclerosis

BACKGROUND: Mitochondrial dysfunction is an established feature of multiple sclerosis (MS). We recently described high levels of mitochondrial DNA (mtDNA) deletions within respiratory enzyme-deficient (lacking mitochondrial respiratory chain complex IV with intact complex II) neurons and choroid plexus epithelial cells in progressive MS. OBJECTIVES: The objective of this paper is to determine whether respiratory enzyme deficiency and mtDNA deletions in MS were in excess of age-related changes within muscle, which, like neurons, are post-mitotic cells that frequently harbour mtDNA deletions with ageing and in disease. METHODS: In progressive MS cases (n=17), known to harbour an excess of mtDNA deletions in the central nervous system (CNS), and controls (n=15), we studied muscle (paraspinal) and explored mitochondria in single fibres. Histochemistry, immunohistochemistry, laser microdissection, real-time polymerase chain reaction (PCR), long-range PCR and sequencing were used to resolve the single muscle fibres. RESULTS: The percentage of respiratory enzyme-deficient muscle fibres, mtDNA deletion level and percentage of muscle fibres harbouring high levels of mtDNA deletions were not significantly different in MS compared with controls. CONCLUSION: Our findings do not provide support to the existence of a diffuse mitochondrial abnormality involving multiple systems in MS. Understanding the cause(s) of the CNS mitochondrial dysfunction in progressive MS remains a research priority

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Path analysis of the relationship between optimism, humor, affectivity, and marital satisfaction among infertile couples

Marital satisfaction is an important factor for establishing a family relationship, feeling satisfied, and living happily together. The aim of the present study was to investigate the relationship between optimism, humor, positive and negative affect, and marital satisfaction among infertile couples. The sample comprised 80 infertile Iranian couples (n = 160) who visited infertility clinics. Participants completed a series of Persian versions of psychometric scales related to optimism (Attributional Style Questionnaire), humor (Humor Styles Questionnaire), marital satisfaction (Enrich Marital Satisfaction Questionnaire), positive affect (PA) and negative affect (NA) (Positive and Negative Affect Schedule). The obtained result of Smart PLS statistical analysis confirmed the significant positive correlation between optimism and humor with marital satisfaction and high PA and low NA. Moreover, the findings also provided an adequate fit of the model. The findings demonstrated that infertile couples high in optimism and humor have higher levels of marital satisfaction and high PA and low PA. Based on the study’s findings, interventions for facilitating optimism and humor among infertile couples are discussed

Building and Combining Matching Algorithms

International audienceThe concept of matching is ubiquitous in declarative programming and in automated reasoning. For instance, it is a key mechanism to run rule-based programs and to simplify clauses generated by theorem provers. A matching problem can be seen as a particular conjunction of equations where each equation has a ground side. We give an overview of techniques that can be applied to build and combine matching algorithms. First, we survey mutation-based techniques as a way to build a generic matching algorithm for a large class of equational theories. Second, combination techniques are introduced to get combined matching algorithms for disjoint unions of theories. Then we show how these combination algorithms can be extended to handle non-disjoint unions of theories sharing only constructors. These extensions are possible if an appropriate notion of normal form is computable

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Hybrid cognitive-behaviour therapy for individuals with insomnia and chronic pain : a pilot randomised controlled trial

Objective Insomnia is a debilitating comorbidity of chronic pain. This pilot trial tested the utility of a hybrid treatment that simultaneously targets insomnia and pain-related interference. Methods Chronic pain patients with clinical insomnia were randomly allocated to receive 4 weekly 2-hour sessions of hybrid treatment (Hybrid Group; n=10) or to keep a pain and sleep diary for 4 weeks, before receiving the hybrid treatment (Monitoring Group; n=10). Participants were assessed at the beginning and end of this 4-week period. Primary outcomes were insomnia severity and pain interference. Secondary outcomes were fatigue, anxiety, depression and pain intensity. Ancillary information about the hybrid treatment’s effect on psychological processes and sleep (as measured with sleep diary and actigraphy) are also presented, alongside data demonstrating the treatment’s clinical significance, acceptability and durability after one and six months. Data from all participants (n=20) were combined for this purpose. Results Compared to symptom monitoring, the hybrid intervention was associated with greater improvement in sleep (as measured with the Insomnia Severity Index and sleep diary) at post-treatment. Although pain intensity did not change, the Hybrid Group reported greater reductions in pain interference, fatigue and depression than the Monitoring Group. Overall, changes associated with the hybrid intervention were clinically significant and durable at 1- and 6-month follow-ups. Participants also rated highly on treatment acceptability. Conclusion The hybrid intervention appeared to be an effective treatment for chronic pain patients with insomnia. It may be a treatment approach more suited to tackle challenges presented in clinical practice, where problems seldom occur in isolation

Synthesis and In vitro antioxidant activity of new 3-substituted-2-oxindole derivatives

A series of new 1,3-dihydro-3-hydroxy-3-(2-phenyl-2-oxoethyl)-2H-indol-2-ones (1a-g) and 1,3-dihydro-3-(2-phenyl-2-oxoethylidene)-2H-indol-2-ones (2a-g) were synthesised by Knoevenagel condensation of substituted indole-2,3-diones (isatins) with various acetophenones. The synthesised compounds were characterised by their physical data, elemental, IR, 1 H NMR, 13 C NMR and mass spectral analyses and their in vitro antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay. These compounds showed moderate to good antioxidant activities as compared with the standard, ascorbic acid. The antioxidant potential of 3-hydroxy-3-substituted oxindoles (1a-g) increased in a concentration-dependent manner from 10 to 500 μg/ml with 5-fluoro and 5-methyl analogues showing maximum activity. Of 3-aroyl methylene indol-2-ones (2a-g), majority of compounds with halogen substitution at position 5 of isatin ring exhibited good antioxidant activity within a concentration range of 5-100 μg/ml and the maximum activity was observed at 20 and 25 μg/ml concentrations. Thus, our study provides evidence that some newly synthesised isatin derivatives exhibit substantial antioxidant activity at low concentrations