ETLP: Event-based Three-factor Local Plasticity for online learning with neuromorphic hardware

Neuromorphic perception with event-based sensors, asynchronous hardware and spiking neurons is showing promising results for real-time and energy-efficient inference in embedded systems. The next promise of brain-inspired computing is to enable adaptation to changes at the edge with online learning. However, the parallel and distributed architectures of neuromorphic hardware based on co-localized compute and memory imposes locality constraints to the on-chip learning rules. We propose in this work the Event-based Three-factor Local Plasticity (ETLP) rule that uses (1) the pre-synaptic spike trace, (2) the post-synaptic membrane voltage and (3) a third factor in the form of projected labels with no error calculation, that also serve as update triggers. We apply ETLP with feedforward and recurrent spiking neural networks on visual and auditory event-based pattern recognition, and compare it to Back-Propagation Through Time (BPTT) and eProp. We show a competitive performance in accuracy with a clear advantage in the computational complexity for ETLP. We also show that when using local plasticity, threshold adaptation in spiking neurons and a recurrent topology are necessary to learn spatio-temporal patterns with a rich temporal structure. Finally, we provide a proof of concept hardware implementation of ETLP on FPGA to highlight the simplicity of its computational primitives and how they can be mapped into neuromorphic hardware for online learning with low-energy consumption and real-time interaction

Effect of zinc intake on growth in infants: A meta-analysis

A systematic review and meta-analysis of available randomized controlled trials (RCTs) was conducted to evaluate the effect of zinc (Zn) intake on growth in infants. Out of 5500 studies identified through electronic searches and reference lists, 19 RCTs were selected after applying the exclusion/inclusion criteria. The influence of Zn intake on growth was considered in the overall meta-analysis. Other variables were also taken into account as possible effect modifiers: doses of Zn intake, intervention duration, nutritional status, and risk of bias. From each select growth study, final measures of weight, length, mid upper arm circumference (MUAC), head circumference, weight for age z-score (WAZ), length for age z-score (LAZ), and weight for length z-score (WLZ) were assessed. Pooled β and 95% confidence interval (CI) were calculated. Additionally, we carried out a sensitivity analysis. Zn intake was not associated with weight, length, MUAC, head circumference, and LAZ in the pooled analyses. However, Zn intake had a positive and statistically effect on WAZ (β = 0.06; 95%CI 0.02 to 0.10) and WLZ (β = 0.05; 95%CI 0.01 to 0.08). The dose–response relationship between Zn intake and these parameters indicated that a doubling of Zn intake increased WAZ and WLZ by approximately 4%. Substantial heterogeneity was present only in length analyses (I2 = 45%; p = 0.03). Zn intake was positively associated with length values at short time (four to 20 weeks) (β = 0.01; CI 95% 0 to 0.02) and at medium doses of Zn (4.1 to 8 mg/day) (β = 0.003; CI 95% 0 to 0.01). Nevertheless, the effect magnitude was small. Our results indicate that Zn intake increases growth parameters of infants. Nonetheless, interpretation of these results should be carefully considered

Singular Temperatures Connected to Charge Transport Mechanism Transitions in Perylene Bisimides from Steady-State Photocurrent Measurements

Perylene bisimides (PBIs) are n-type semiconducting and photogenerating materials widely used in a variety of optoelectronic devices. Particularly interesting are PBIs that are simultaneously water-soluble and liquid-crystalline (PBI-W+LC) and, thus, attractive for the development of high-performing easily processable applications in biology and “green” organic electronics. In this work, singular temperatures connected to charge transport mechanism transitions in a PBI-W+LC derivative are determined with high accuracy by means of temperature-dependent photocurrent studies. These singular temperatures include not only the ones observed at 60 and 110 °C, corresponding to phase transition temperatures from crystalline to liquid-crystalline (LC) and from LC to the isotropic phase, respectively, as confirmed by differential scanning calorimetry (DSC), but also a transition at 45 °C, not observed by DSC. By analyzing the photocurrent dependence simultaneously on temperature and on light intensity, this transition is interpreted as a change from monomolecular to bimolecular recombination. These results might be useful for other semiconducting photogenerating materials, not necessarily PBIs or even organic semiconductors, which also show transport behavior changes at singular temperatures not connected with structural or phase transitions.We appreciate support from the Spanish government (MINECO) and the European Community (FEDER) through Grant MAT-2011-28167-C02-01, as well as the University of Alicante. We gratefully acknowledge financial support from MINECO (MAT2014-52305-P) and the UCM-BSCH joint project (GR3/14-910759). A. de la Peña thanks Universidad Complutense for a predoctoral fellowship

WaLiN-GUI: a graphical and auditory tool for neuron-based encoding

Neuromorphic computing relies on spike-based, energy-efficient communication, inherently implying the need for conversion between real-valued (sensory) data and binary, sparse spiking representation. This is usually accomplished using the real valued data as current input to a spiking neuron model, and tuning the neuron's parameters to match a desired, often biologically inspired behaviour. We developed a tool, the WaLiN-GUI, that supports the investigation of neuron models and parameter combinations to identify suitable configurations for neuron-based encoding of sample-based data into spike trains. Due to the generalized LIF model implemented by default, next to the LIF and Izhikevich neuron models, many spiking behaviors can be investigated out of the box, thus offering the possibility of tuning biologically plausible responses to the input data. The GUI is provided open source and with documentation, being easy to extend with further neuron models and personalize with data analysis functions.Comment: 4 pages, 1 figur

Nutritional problems perceived by pediatricians in Spanish children younger than 3 years

Introducción: Los padres son los principales responsables de la educación nutricional de sus hijos y es labor del pediatra orientar y resolver problemas al respecto. En este estudio se pretende conocer la relevancia de las cuestiones nutricionales en la consulta del pediatra y los principales problemas nutricionales percibidos en los menores de 3 años. Métodos: Estudio descriptivo, transversal en dos fases. La primera consistió en entrevistas y grupos de discusión con 30 pediatras seleccionados aleatoriamente en Madrid y Barcelona. Los resultados se utilizaron para diseñar el cuestionario online (76 preguntas relacionadas con la nutrición en niños de 0-3 años) de la siguiente fase, en la que participaron pediatras seleccionados de forma aleatoria y representativa del territorio nacional. Resultados: De 258 pediatras seleccionados, completaron el cuestionario 151, que atendían a una media de 588 pacientes/mes. Los principales problemas nutricionales percibidos hasta los 12 meses fueron las deficiencias de hierro y vitaminas y la escasa ganancia de peso, y posteriormente la ingesta excesiva de carbohidratos y lípidos y el sobrepeso. Los padres fueron considerados los actores principales en la salud nutricional de sus hijos, pero su preocupación por esta cuestión se reduce significativamente (p < 0,0001) con la edad del niño. Los aspectos considerados más importantes para obtener unos buenos hábitos alimentarios fueron la alimentación adaptada a las necesidades del niño y respetar el tiempo de sueño. El porcentaje de pacientes que recibe recomendaciones de hábitos nutricionales varió del 88% (0-6 meses) al 61% (24-36 meses). Conclusiones: A pesar de considerar la salud nutricional importante, la intervención educativa del pediatra al respecto no es óptima. Los problemas nutricionales percibidos fueron distintos según la edadIntroduction: Parents are most responsible for nutritional education of children, and pediatritians must advise and help them with their doubts. The purpose of this study was to know the relevance of nutritional topics in daily practice and the main nutritional problems perceived by pediatritians in children under 3 years of age. Methods: Descriptive, cross-sectional study performed in 2 stages. First stage consisted on discussion meetings with 30 random-selected pediatritians from Madrid and Barcelona. Results were used to design the on-line questionnaire of the second stage (76 questions related to nutrition in children under 3 years). A random and representative sample of Spanish pediatritians was selected for this stage. Results: One hundred and fifty one pediatritians, among 258 sampled, completed the questionnaire. They referred to see a mean of 588 patients/month. The main perceived nutritional problems in the first year of life were iron and vitamin deficiencies and poor weight gain. In the next months, excess in carbohydrates and lipid intake and overweight were the main problems perceived. Parents were considered the main actors regarding their children’s nutritional health, but their concern in these questions significantly reduced with children’s age (p < 0,0001). Factors considered to have the greatest relevance in the acquisition of good nutritional habits were to provide a diet adjusted for children’s requirements and to observe the appropriate sleeping hours. The proportion of children who receive nutritional counseling varied from 88% (0-6 months) to 61% (24-36 months). Conclusions: Despite of the relevance given by pediatritians, educational intervention regarding nutritional health is not ideal. Nutritional problems perceived by pediatritians varied with children’s ageEste estudio ha sido financiado por Almiron/Danone Baby Nutrition

Perspectives of Cognitive Impairment and Behavioral Disturbances in Parkinson’s Disease Dementia

Parkinson’s disease dementia is a critical stage of the disease because that has a negative impact on the quality of life and functional independence in activities daily living. How the cognition progress to dementia is a key to be explored. The cognitive impairment shows two profiles: cortical (memory encoding, visuospatial abilities, and language) and subcortical, with a dysexecutive syndrome that includes deficits in recognition memory, attention processes, and visual perception as well as visual hallucinations and cognitive fluctuations. Behavioral problems such as apathy, anxiety, depression, and impulse control disorders take a significant part in the loss of autonomy and progression of the disease. To detect the risk of Parkinson’s disease dementia development, the integral evaluation of patients in all stages of the disease should consider the interplay of genetic and epigenetic factors, motor subtypes, and non-motor symptoms (NMS) in order to implement different therapeutics and supportive strategies when they are likely to have efficacy

Identification of clinical variants beyond the exome in inborn errors of metabolism

Inborn errors of metabolism (IEM) constitute a huge group of rare diseases affecting 1 in every 1000 newborns. Next-generation sequencing has transformed the diagnosis of IEM, leading to its proposed use as a second-tier technology for confirming cases detected by clinical/biochemical studies or newborn screening. The diagnosis rate is, however, still not 100%. This paper reports the use of a personalized multi-omics (metabolomic, genomic and transcriptomic) pipeline plus functional genomics to aid in the genetic diagnosis of six unsolved cases, with a clinical and/or biochemical diagnosis of galactosemia, mucopolysaccharidosis type I (MPS I), maple syrup urine disease (MSUD), hyperphenylalaninemia (HPA), citrullinemia, or urea cycle deficiency. Eight novel variants in six genes were identified: six (four of them deep intronic) located in GALE, IDUA, PTS, ASS1 and OTC, all affecting the splicing process, and two located in the promoters of IDUA and PTS, thus affecting these genes’ expression. All the new variants were subjected to functional analysis to verify their pathogenic effects. This work underscores how the combination of different omics technologies and functional analysis can solve elusive cases in clinical practic

Switching to Glycerol Phenylbutyrate in 48 Patients with Urea Cycle Disorders: Clinical Experience in Spain

Background and objectives: Glycerol phenylbutyrate (GPB) has demonstrated safety and efficacy in patients with urea cycle disorders (UCDs) by means of its clinical trial program, but there are limited data in clinical practice. In order to analyze the efficacy and safety of GPB in clinical practice, here we present a national Spanish experience after direct switching from another nitrogen scavenger to GPB. Methods: This observational, retrospective, multicenter study was performed in 48 UCD patients (age 11.7 ± 8.2 years) switching to GPB in 13 centers from nine Spanish regions. Clinical, biochemical, and nutritional data were collected at three different times: prior to GPB introduction, at first follow-up assessment, and after one year of GPB treatment. Number of related adverse effects and hyperammonemic crisis 12 months before and after GPB introduction were recorded. Results: GPB was administered at a 247.8 ± 102.1 mg/kg/day dose, compared to 262.6 ± 126.1 mg/kg/day of previous scavenger (46/48 Na-phenylbutyrate). At first follow-up (79 ± 59 days), a statistically significant reduction in ammonia (from 40.2 ± 17.3 to 32.6 ± 13.9 μmol/L, p < 0.001) and glutamine levels (from 791.4 ± 289.8 to 648.6 ± 247.41 μmol/L, p < 0.001) was observed. After one year of GPB treatment (411 ± 92 days), we observed an improved metabolic control (maintenance of ammonia and glutamine reduction, with improved branched chain amino acids profile), and a reduction in hyperammonemic crisis rate (from 0.3 ± 0.7 to less than 0.1 ± 0.3 crisis/patients/year, p = 0.02) and related adverse effects (RAE, from 0.5 to less than 0.1 RAEs/patients/year p < 0.001). Conclusions: This study demonstrates the safety of direct switching from other nitrogen scavengers to GPB in clinical practice, which improves efficacy, metabolic control, and RAE compared to previous treatments.This study was funded by AECOM (Spanish Association for the Study of Inborn Errors of Metabolism). Immedica Pharma Spain funded medical writing support and article processing charges

Influence of Milk-Feeding Type and Genetic Risk of Developing Coeliac Disease on Intestinal Microbiota of Infants: The PROFICEL Study

Interactions between environmental factors and predisposing genes could be involved in the development of coeliac disease (CD). This study has assessed whether milk-feeding type and HLA-genotype influence the intestinal microbiota composition of infants with a family history of CD. The study included 164 healthy newborns, with at least one first-degree relative with CD, classified according to their HLA-DQ genotype by PCR-SSP DQB1 and DQA1 typing. Faecal microbiota was analysed by quantitative PCR at 7 days, and at 1 and 4 months of age. Significant interactions between milk-feeding type and HLA-DQ genotype on bacterial numbers were not detected by applying a linear mixed-model analysis for repeated measures. In the whole population, breast-feeding promoted colonization of C. leptum group, B. longum and B. breve, while formula-feeding promoted that of Bacteroides fragilis group, C. coccoides-E. rectale group, E. coli and B. lactis. Moreover, increased numbers of B. fragilis group and Staphylococcus spp., and reduced numbers of Bifidobacterium spp. and B. longum were detected in infants with increased genetic risk of developing CD. Analyses within subgroups of either breast-fed or formula-fed infants indicated that in both cases increased risk of CD was associated with lower numbers of B. longum and/or Bifidobacterium spp. In addition, in breast-fed infants the increased genetic risk of developing CD was associated with increased C. leptum group numbers, while in formula-fed infants it was associated with increased Staphylococcus and B. fragilis group numbers. Overall, milk-feeding type in conjunction with HLA-DQ genotype play a role in establishing infants' gut microbiota; moreover, breast-feeding reduced the genotype-related differences in microbiota composition, which could partly explain the protective role attributed to breast milk in this disorder

Overview of recent TJ-II stellarator results

The main results obtained in the TJ-II stellarator in the last two years are reported. The most important topics investigated have been modelling and validation of impurity transport, validation of gyrokinetic simulations, turbulence characterisation, effect of magnetic configuration on transport, fuelling with pellet injection, fast particles and liquid metal plasma facing components. As regards impurity transport research, a number of working lines exploring several recently discovered effects have been developed: the effect of tangential drifts on stellarator neoclassical transport, the impurity flux driven by electric fields tangent to magnetic surfaces and attempts of experimental validation with Doppler reflectometry of the variation of the radial electric field on the flux surface. Concerning gyrokinetic simulations, two validation activities have been performed, the comparison with measurements of zonal flow relaxation in pellet-induced fast transients and the comparison with experimental poloidal variation of fluctuations amplitude. The impact of radial electric fields on turbulence spreading in the edge and scrape-off layer has been also experimentally characterized using a 2D Langmuir probe array. Another remarkable piece of work has been the investigation of the radial propagation of small temperature perturbations using transfer entropy. Research on the physics and modelling of plasma core fuelling with pellet and tracer-encapsulated solid-pellet injection has produced also relevant results. Neutral beam injection driven Alfvénic activity and its possible control by electron cyclotron current drive has been examined as well in TJ-II. Finally, recent results on alternative plasma facing components based on liquid metals are also presented. ISSN:0029-5515 ISSN:1741-432