Developmental Trajectories of Letter and Speech Sound Integration During Reading Acquisition

Reading acquisition in alphabetic languages starts with learning the associations between speech sounds and letters. This learning process is related to crucial developmental changes of brain regions that serve visual, auditory, multisensory integration, and higher cognitive processes. Here, we studied the development of audiovisual processing and integration of letter-speech sound pairs with an audiovisual target detection functional MRI paradigm. Using a longitudinal approach, we tested children with varying reading outcomes before the start of reading acquisition (T1, 6.5 yo), in first grade (T2, 7.5 yo), and in second grade (T3, 8.5 yo). Early audiovisual integration effects were characterized by higher activation for incongruent than congruent letter-speech sound pairs in the inferior frontal gyrus and ventral occipitotemporal cortex. Audiovisual processing in the left superior temporal gyrus significantly increased from the prereading (T1) to early reading stages (T2, T3). Region of interest analyses revealed that activation in left superior temporal gyrus (STG), inferior frontal gyrus and ventral occipitotemporal cortex increased in children with typical reading fluency skills, while poor readers did not show the same development in these regions. The incongruency effect bilaterally in parts of the STG and insular cortex at T1 was significantly associated with reading fluency skills at T3. These findings provide new insights into the development of the brain circuitry involved in audiovisual processing of letters, the building blocks of words, and reveal early markers of audiovisual integration that may be predictive of reading outcomes

Visual Occipito-Temporal N1 Sensitivity to Digits Across Elementary School

Number processing abilities are important for academic and personal development. The course of initial specialization of ventral occipito-temporal cortex (vOTC) sensitivity to visual number processing is crucial for the acquisition of numeric and arithmetic skills. We examined the visual N1, the electrophysiological correlate of vOTC activation across five time points in kindergarten (T1, mean age 6.60 years), middle and end of first grade (T2, 7.38 years; T3, 7.68 years), second grade (T4, 8.28 years), and fifth grade (T5, 11.40 years). A combination of cross-sectional and longitudinal EEG data of a total of 62 children (35 female) at varying familial risk for dyslexia were available to form groups of 23, 22, 27, 27, and 42 participants for each of the five time points. The children performed a target detection task which included visual presentation of single digits (DIG), false fonts (FF), and letters (LET) to derive measures for coarse (DIG vs. FF) and fine (DIG vs. LET) digit sensitive processing across development. The N1 amplitude analyses indicated coarse and fine sensitivity characterized by a stronger N1 to digits than false fonts across all five time points, and stronger N1 to digits than letters at all but the second (T2) time point. In addition, lower arithmetic skills were associated with stronger coarse N1 digit sensitivity over the left hemisphere in second grade (T4), possibly reflecting allocation of more attentional resources or stronger reliance on the verbal system in children with poorer arithmetic skills. To summarize, our results show persistent visual N1 sensitivity to digits that is already present early on in pre-school and remains stable until fifth grade. This pattern of digit sensitivity development clearly differs from the relatively sharp rise and fall of the visual N1 sensitivity to words or letters between kindergarten and middle of elementary school and suggests unique developmental trajectories for visual processing of written characters that are relevant to numeracy and literacy

Disentangling influences of dyslexia, development, and reading experience on effective brain connectivity in children

Altered brain connectivity between regions of the reading network has been associated with reading difficulties. However, it remains unclear whether connectivity differences between children with dyslexia (DYS) and those with typical reading skills (TR) are specific to reading impairments or to reading experience. In this functional MRI study, 132 children (M = 10.06 y, SD = 1.46) performed a phonological lexical decision task. We aimed to disentangle (1) disorder-specific from (2) experience-related differences in effective connectivity and to (3) characterize the development of DYS and TR. We applied dynamic causal modeling to age-matched (ndys = 25, nTR = 35) and reading-level-matched (ndys = 25, nTR = 22) groups. Developmental effects were assessed in beginning and advanced readers (TR: nbeg = 48, nadv = 35, DYS: nbeg = 24, nadv = 25). We show that altered feedback connectivity between the inferior parietal lobule and the visual word form area (VWFA) during print processing can be specifically attributed to reading impairments, because these alterations were found in DYS compared to both the age-matched and reading-level-matched TR. In contrast, feedforward connectivity from the VWFA to parietal and frontal regions characterized experience in TR and increased with age and reading skill. These directed connectivity findings pinpoint disorder-specific and experience-dependent alterations in the brain's reading network. Keywords: Development; Developmental dyslexia; Dynamic causal modeling (DCM); Effective connectivity; Inferior parietal lobule; Reading network; Visual Word Forma Area (VWFA); fMRI

Visual Occipito-Temporal N1 Sensitivity to Digits Across Elementary School

Number processing abilities are important for academic and personal development. The course of initial specialization of ventral occipito-temporal cortex (vOTC) sensitivity to visual number processing is crucial for the acquisition of numeric and arithmetic skills. We examined the visual N1, the electrophysiological correlate of vOTC activation across five time points in kindergarten (T1, mean age 6.60 years), middle and end of first grade (T2, 7.38 years; T3, 7.68 years), second grade (T4, 8.28 years), and fifth grade (T5, 11.40 years). A combination of cross-sectional and longitudinal EEG data of a total of 62 children (35 female) at varying familial risk for dyslexia were available to form groups of 23, 22, 27, 27, and 42 participants for each of the five time points. The children performed a target detection task which included visual presentation of single digits (DIG), false fonts (FF), and letters (LET) to derive measures for coarse (DIG vs. FF) and fine (DIG vs. LET) digit sensitive processing across development. The N1 amplitude analyses indicated coarse and fine sensitivity characterized by a stronger N1 to digits than false fonts across all five time points, and stronger N1 to digits than letters at all but the second (T2) time point. In addition, lower arithmetic skills were associated with stronger coarse N1 digit sensitivity over the left hemisphere in second grade (T4), possibly reflecting allocation of more attentional resources or stronger reliance on the verbal system in children with poorer arithmetic skills. To summarize, our results show persistent visual N1 sensitivity to digits that is already present early on in pre-school and remains stable until fifth grade. This pattern of digit sensitivity development clearly differs from the relatively sharp rise and fall of the visual N1 sensitivity to words or letters between kindergarten and middle of elementary school and suggests unique developmental trajectories for visual processing of written characters that are relevant to numeracy and literacy

WhoLoDancE: Towards a methodology for selecting Motion Capture Data across different Dance Learning Practice

<p>In this paper we present the objectives and preliminary work of WhoLoDancE a Research and Innovation Action funded under the European Union‘s Horizon 2020 programme, aiming at using new technologies for capturing and analyzing dance movement to facilitate whole-body interaction learning experiences for a variety of dance genres. Dance is a diverse and heterogeneous practice and WhoLoDancE will develop a protocol for the creation and/or selection of dance sequences drawn from different dance styles for different teaching and learning modalities. As dance learning practice lacks standardization beyond dance genres and specific schools and techniques, one of the first project challenges is to bring together a variety of dance genres and teaching practices and work towards a methodology for selecting the appropriate shots for motion capturing, to acquire kinetic material which will provide a satisfying proof of concept for Learning scenarios of particular genres. The four use cases we are investigating are 1) classical ballet, 2) contemporary dance, 3) flamenco and 4) Greek folk dance.</p

Modulating Activity of Vancomycin and Daptomycin on the Expression of Autolysis Cell-Wall Turnover and Membrane Charge Genes in hVISA and VISA Strains

Glycopeptides are still the gold standard to treat MRSA (Methicillin Resistant Staphylococcus aureus) infections, but their widespread use has led to vancomycin-reduced susceptibility [heterogeneous Vancomycin-Intermediate-Staphylococcus aureus (hVISA) and Vancomycin-Intermediate-Staphylococcus aureus (VISA)], in which different genetic loci (regulatory, autolytic, cell-wall turnover and cell-envelope positive charge genes) are involved. In addition, reduced susceptibility to vancomycin can influence the development of resistance to daptomycin. Although the phenotypic and molecular changes of hVISA/VISA have been the focus of different papers, the molecular mechanisms responsible for these different phenotypes and for the vancomycin and daptomycin cross-resistance are not clearly understood. The aim of our study was to investigate, by real time RT-PCR, the relative quantitative expression of genes involved in autolysis (atl-lytM), cell-wall turnover (sceD), membrane charges (mprF-dltA) and regulatory mechanisms (agr-locus-graRS-walKR), in hVISA and VISA cultured with or without vancomycin and daptomycin, in order to better understand the molecular basis of vancomycin-reduced susceptibility and the modulating activity of vancomycin and daptomycin on the expression of genes implicated in their reduced susceptibility mechanisms. Our results show that hVISA and VISA present common features that distinguish them from Vancomycin-Susceptible Staphylococcus aureus (VSSA), responsible for the intermediate glycopeptide resistance i.e. an increased cell-wall turnover, an increased positive cell-wall charge responsible for a repulsion mechanism towards vancomycin and daptomycin, and reduced agr-functionality. Indeed, VISA emerges from hVISA when VISA acquires a reduced autolysis caused by a down-regulation of autolysin genes, atl/lytM, and a reduction of the net negative cell-envelope charge via dltA over-expression. Vancomycin and daptomycin, acting in a similar manner in hVISA and VISA, can influence their cross-resistance mechanisms promoting VISA behavior in hVISA and enhancing the cell-wall pathways responsible for the intermediate vancomycin resistance in VISA. Daptomycin can also induce a charge repulsion mechanism both in hVISA and VISA increasing the activity of the mprF

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81&nbsp;years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population