A neuro-inspired system for online learning and recognition of parallel spike trains, based on spike latency and heterosynaptic STDP

Humans perform remarkably well in many cognitive tasks including pattern recognition. However, the neuronal mechanisms underlying this process are not well understood. Nevertheless, artificial neural networks, inspired in brain circuits, have been designed and used to tackle spatio-temporal pattern recognition tasks. In this paper we present a multineuronal spike pattern detection structure able to autonomously implement online learning and recognition of parallel spike sequences (i.e., sequences of pulses belonging to different neurons/neural ensembles). The operating principle of this structure is based on two spiking/synaptic neurocomputational characteristics: spike latency, that enables neurons to fire spikes with a certain delay and heterosynaptic plasticity, that allows the own regulation of synaptic weights. From the perspective of the information representation, the structure allows mapping a spatio-temporal stimulus into a multidimensional, temporal, feature space. In this space, the parameter coordinate and the time at which a neuron fires represent one specific feature. In this sense, each feature can be considered to span a single temporal axis. We applied our proposed scheme to experimental data obtained from a motor inhibitory cognitive task. The test exhibits good classification performance, indicating the adequateness of our approach. In addition to its effectiveness, its simplicity and low computational cost suggest a large scale implementation for real time recognition applications in several areas, such as brain computer interface, personal biometrics authentication or early detection of diseases.Comment: Submitted to Frontiers in Neuroscienc

Anxiety and risk of vascular dementia in an elderly community sample: The role of sex

Background: To assess the association between anxiety and risk of vascular dementia (VaD), as well as potential sex differences, in a community-based cohort. Methods: A random sample of 4057 dementia-free community participants aged 55 or older, from the longitudinal, community-based Zaragoza Dementia and Depression Project (ZARADEMP) study were followed for 4.5 years. Geriatric Mental State B (GMS)-Automated Geriatric Examination for Computer Assisted Taxonomy (AGECAT) was used for the assessment and diagnosis of anxiety, and a panel of research psychiatrists diagnosed the incident cases of VaD according to DSM-IV (Diagnostic and Statistical Manual of mental disordes). Multivariate survival analysis with competing risk regression model was performed. Results: In men, the incidence rate of VaD was significantly higher among anxiety subjects compared with non-anxiety subjects (incidence rate ratio (IRR) (95% confidence interval (CI)): 3.24 (1.13–9.35); p = 0.029), and no difference was observed in women (IRR (95%CI): 0.68 (0.19– 2.23); p = 0.168). In the multivariate model, for men, cases of anxiety had 2.6-fold higher risk of VaD (subdistribution hazard ratio (SHR): 2.61; 95%CI: 0.88–7.74) when all potential confounding factors were controlled, with no statistical significance (p = 0.084), but a clinically relevant effect (Cohen’s d: 0.74). No association was found in women. Conclusions: In men, but not in women, risk of VaD was higher among individuals with anxiety, with a clinically relevant effect. Potential anxiety-related preventive interventions for VaD might be tailored to men and women separately

miR-21 Promotes Fibrogenesis in Peritoneal Dialysis.

Peritoneal dialysis (PD) is a life-saving form of renal replacement therapy for those with end-stage kidney disease. Mesothelial cells (MCs) line the peritoneal cavity and help define peritoneal response to treatment-associated injury, a major reason for treatment failure. miRNAs are important regulators, but their roles in peritoneal fibrosis are largely unknown. In this study, miR-21 was one of the most abundant miRNAs in primary MCs, and was up-regulated by the profibrotic cytokine transforming growth factor-β1 and in PD effluent-derived MCs exhibiting mesenchymal phenotypic change. Increased miR-21 was found in peritoneal membrane biopsy specimens from PD patients compared to healthy controls (PD biocompatible, 5.86×, P = 0.0001; PD conventional, 7.09×, P < 0.0001, n = 11 per group). In PD effluent from a cohort of 230 patients, miR-21 was higher in those receiving the therapy long-term compared to new starters (n = 230, miR-21 3.26×, P = 0.001) and associated with icodextrin use (R = 0.52; 95% CI, 0.20-0.84), peritonitis count (R = 0.16; 95% CI, 0.03-0.29), and dialysate cytokines. miR-21 down-regulated programmed cell death 4 and programmed cell death 4 protein was decreased in peritoneal membrane biopsy specimens from PD patients compared to healthy controls. New miR-21 targets were identified that may be important during PD fibrogenesis. These data identify miR-21 as an important effector of fibrosis in the peritoneal membrane, and a promising biomarker in the dialysis effluent for membrane change in patients receiving PD

Clinically significant anxiety as a risk factor for dementia in the elderly community

Objective: To evaluate whether clinically significant anxiety is an independent risk factor for dementia, taking into account both depression among potentially confounding factors and the competing risk of death. Method: During the Zaragoza Dementia and Depression (ZARADEMP) study, a random sample of community dwellers aged 55 years or older was assessed (n = 4803), and a two-wave, 4.5-year follow-up was completed. Geriatric Mental State (GMS)-AGECAT criteria were used to diagnose anxiety and DSM-IV criteria were applied to diagnose incident dementia. The multivariate Fine and Gray regression model was implemented to calculate dementia risk. Results: Compared with non-cases (GMS-AGECAT criteria), the incidence rate of dementia was significantly higher in subcases of anxiety, and particularly significant in the cases of anxiety (incidence rate ratio (IRR): 2.77; P = 0.010). Cases of anxiety, but not subcases, at baseline were significantly associated with dementia risk (adjusted subdistribution hazard ratio (SHR): 2.7; P = 0.019). Conclusion: Clinically significant anxiety is associated with an almost threefold increase in the risk of dementia in the population, even when controlling for depression and considering mortality in the competing risks model

Geochemical speciation of mercury in bauxite

The presence of trace concentrations of mercury in bauxite is a potential environmental concern in the Bayer alumina refining process. An understanding of the geochemical speciation of mercury in bauxite provides insight into the behaviour of mercury in the Bayer process. The speciation of mercury was evaluated using a novel continuous thermal desorption methodology, sequential extractions, alkaline digestion, aqua regia digestion and hydrofluoric acid total dissolution assay. Thermal desorption demonstrated two distinct mercury forms. Labile mercury was found to be present as metacinnabar or organic-associated mercury, while refractory mercury was associated with quartz or other refractory silicates

Benchmarking High-Field Few-Electron Correlation and QED Contributions in Hg⁷⁵⁺ to Hg⁷⁸⁺ Ions. II. Theory

Theoretical resonance energies for KLL dielectronic recombination into He-, Li-, Be-, and B-like Hg ions are calculated by various means and discussed in detail. We apply the multiconfiguration Dirac-Fock and the configuration interaction Dirac-Fock-Sturmian methods, and quantum electrodynamic many-body theory. The different contributions such as relativistic electron interaction, quantum electrodynamic contributions, and finite nuclear size and mass corrections are calculated and their respective theoretical uncertainties are estimated. Our final results are compared to experimental data from the preceding paper. The comparison of theoretical values with the experimental energies shows a good overall agreement for most transitions and illustrates the significance of relativistic electron interaction contributions including correlation, magnetic, and retardation effects and quantum electrodynamic corrections. A few discrepancies found in specific recombination resonances for initially Li- and Be-like Hg ions are pointed out, suggesting the need for further theoretical and experimental studies along these isoelectronic sequences

Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure–response analysis

Purpose: This study assessed the effect of lurbinectedin, a highly selective inhibitor of oncogenic transcription, on the change from baseline in Fridericia’s corrected QT interval (¿QTcF) and electrocardiography (ECG) morphological patterns, and lurbinectedin concentration–¿QTcF (C-¿QTcF) relationship, in patients with advanced solid tumors. Methods: Patients with QTcF = 500 ms, QRS &lt; 110 ms, PR &lt; 200 ms, and normal cardiac conduction and function received lurbinectedin 3.2 mg/m2 as a 1-h intravenous infusion every 3 weeks. ECGs were collected in triplicate via 12-lead digital recorder in treatment cycle 1 and 2 and analyzed centrally. ECG collection time-matched blood samples were drawn to measure lurbinectedin plasma concentration. No effect on QTc interval was concluded if the upper bound (UB) of the least square (LS) mean two-sided 90% confidence intervals (CI) for ¿QTcF at each time point was &lt; 20 ms. C-¿QTcF was explored using linear mixed-effects analysis. Results: A total of 1707 ECGs were collected from 39 patients (females, 22; median age, 56 years). The largest UB of the 90% CI of ¿QTcF was 9.6 ms, thus lower than the more conservative 10 ms threshold established at the ICH E14 guideline for QT studies in healthy volunteers. C-¿QTcF was better fit by an effect compartment model, and the 90% CI of predicted ¿QTcF at Cmax was 7.81 ms, also below the 10 ms threshold of clinical concern. Conclusions: ECG parameters and C-¿QTcF modelling in this prospective study indicate that lurbinectedin was not associated with a clinically relevant effect on cardiac repolarization

Correlation and Quantum Electrodynamic Effects on the Radiative Lifetime and Relativistic Nuclear Recoil in Ar¹³⁺ and Ar¹⁴⁺ Ions

The radiative lifetime and mass isotope shift of the 1s22s22p 2P3/2 - 2P1/2 M1 transition in Ar13+ ions have been determined with high accuracies using the Heidelberg electron beam ion trap. This fundamentally relativistic transition provides unique possibilities for performing precise studies of correlation and quantum electrodynamic effects in many-electron systems. The lifetime corresponding to the transition has been measured with an accuracy of the order of one per thousand. Theoretical calculations predict a lifetime that is in significant disagreement with this high-precision experimental value. Our mass shift calculations, based on a fully relativistic formulation of the nuclear recoil operator, are in excellent agreement with the experimental results and cofirm the absolute necessity to include relativistic recoil corrections when evaluating mass shift contributions even in medium-Z ions

Relating constructs of attention and working memory to social withdrawal in Alzheimer's disease and schizophrenia: issues regarding paradigm selection

Central nervous system diseases are not currently diagnosed based on knowledge of biological mechanisms underlying their symptoms. Greater understanding may be offered through an agnostic approach to traditional disease categories, where learning more about shared biological mechanisms across conditions could potentially reclassify sub-groups of patients to allow realisation of more effective treatments. This review represents the output of the collaborative group “PRISM”, tasked with considering assay choices for assessment of attention and working memory in a transdiagnostic cohort of Alzheimer''s disease and schizophrenia patients exhibiting symptomatic spectra of social withdrawal. A multidimensional analysis of this nature has not been previously attempted. Nominated assays (continuous performance test III, attention network test, digit symbol substitution, N-back, complex span, spatial navigation in a virtual environment) reflected a necessary compromise between the need for broad assessment of the neuropsychological constructs in question with several pragmatic criteria: patient burden, compatibility with neurophysiologic measures and availability of preclinical homologues

MicroRNAs regulate human brain endothelial cell-barrier function in inflammation: implications for multiple sclerosis.

Blood-brain barrier (BBB) dysfunction is a major hallmark of many neurological diseases, including multiple sclerosis (MS). Using a genomics approach, we defined a microRNA signature that is diminished at the BBB of MS patients. In particular, miR-125a-5p is a key regulator of brain endothelial tightness and immune cell efflux. Our findings suggest that repair of a disturbed BBB through microRNAs may represent a novel avenue for effective treatment of MS