Auditory attention influences trajectories of symbol–speech sound learning in children with and without dyslexia

The acquisition of letter–speech sound correspondences is a fundamental process underlying reading development, one that could be influenced by several linguistic and domain-general cognitive factors. In the current study, we mimicked the first steps of this process by examining behavioral trajectories of audiovisual associative learning in 110 7- to 12-year-old children with and without dyslexia. Children were asked to learn the associations between eight novel symbols and native speech sounds in a brief training and subsequently read words and pseudowords written in the artificial orthography. We then investigated the influence of auditory attention as one of the putative domain-general factors influencing associative learning. To this aim, we assessed children with experimental measures of auditory sustained selective attention and interference control. Our results showed shallower learning trajectories in children with dyslexia, especially during the later phases of the training blocks. Despite this, children with dyslexia performed similarly to typical readers on the post-training reading tests using the artificial orthography. Better auditory sustained selective attention and interference control skills predicted greater response accuracy during training. Sustained selective attention was also associated with the ability to apply these novel correspondences in the reading tests. Although this result has the limitations of a correlational design, it denotes that poor attentional skills may constitute a risk during the early stages of reading acquisition, when children start to learn letter–speech sound associations. Importantly, our findings underscore the importance of examining dynamics of learning in reading acquisition as well as individual differences in more domain-general attentional factors

Attentional modulation of neural sound tracking in children with and without dyslexia

Auditory selective attention forms an important foundation of children's learning by enabling the prioritisation and encoding of relevant stimuli. It may also influence reading development, which relies on metalinguistic skills including the awareness of the sound structure of spoken language. Reports of attentional impairments and speech perception difficulties in noisy environments in dyslexic readers are also suggestive of the putative contribution of auditory attention to reading development. To date, it is unclear whether non-speech selective attention and its underlying neural mechanisms are impaired in children with dyslexia and to which extent these deficits relate to individual reading and speech perception abilities in suboptimal listening conditions. In this EEG study, we assessed non-speech sustained auditory selective attention in 106 7-to-12-year-old children with and without dyslexia. Children attended to one of two tone streams, detecting occasional sequence repeats in the attended stream, and performed a speech-in-speech perception task. Results show that when children directed their attention to one stream, inter-trial-phase-coherence at the attended rate increased in fronto-central sites; this, in turn, was associated with better target detection. Behavioural and neural indices of attention did not systematically differ as a function of dyslexia diagnosis. However, behavioural indices of attention did explain individual differences in reading fluency and speech-in-speech perception abilities: both these skills were impaired in dyslexic readers. Taken together, our results show that children with dyslexia do not show group-level auditory attention deficits but these deficits may represent a risk for developing reading impairments and problems with speech perception in complex acoustic environments. Research Highlights: Non-speech sustained auditory selective attention modulates EEG phase coherence in children with/without dyslexia Children with dyslexia show difficulties in speech-in-speech perception Attention relates to dyslexic readers’ speech-in-speech perception and reading skills Dyslexia diagnosis is not linked to behavioural/EEG indices of auditory attention

A public domain model for 1D temperature and rheology construction in basement-sedimentary geothermal exploration: an application to the Spanish Central System and adjacent basins

Brittle basement and sedimentary rocks, in particular if these are underlain by radiogenic crust, are considered a prime target for enhanced geothermal systems (EGS).They are marked by high geothermal gradients, caused by radiogenic heat production, and are well suited to be used for geothermal doublets after hydraulic stimulation. Critical conditions for successful EGS projects are: (a) tectonic stresses close to failure, allowing creation of induced fractures by means of hydraulic stimulation; (b) sufficient high temperatures [150 C, preferably in excess of 200 C, at depths of less than 5 km; (c) sufficient high water flow rates, to be sustained through induced fractures. For geothermal production, knowledge on thermomechanical properties of the lithosphere provides critical constraints on crustal stresses and basement temperatures. We developed a freely available 1D thermal and rheological model for basement-sedimentary areas. This tool helps to understand variability of deep temperatures, as an effect of uncertainties in thermal and rheological properties and tectonic constraints for the lithosphere, important for assessing geothermal prospectivity. The tool is demonstrated on the Central System in Spain and the adjacent Tajo and Duero basins

The role of 18F-FDG PET in the differentiation between lung metastases and synchronous second primary lung tumours

Contains fulltext : 87717.pdf (publisher's version ) (Closed access)PURPOSE: In lung cancer patients with multiple lesions, the differentiation between metastases and second primary tumours has significant therapeutic and prognostic implications. The aim of this retrospective study was to investigate the potential of (18)F-FDG PET to discriminate metastatic disease from second primary lung tumours. METHODS: Of 1,396 patients evaluated by the thoracic oncology group between January 2004 and April 2009 at the Radboud University Nijmegen Medical Centre, patients with a synchronous second primary lung cancer were selected. Patients with metastatic disease involving the lungs served as the control group. Maximum standardized uptake values (SUVs) measured with (18)F-FDG PET were determined for two tumours in each patient. The relative difference between the SUVs of these tumours (SUV) was determined and compared between the second primary group and metastatic disease group. Receiver-operating characteristic (ROC) curve analysis was performed to determine the sensitivity and specificity of the SUV for an optimal cut-off value. RESULTS: A total of 37 patients (21 metastatic disease, 16 second primary cancer) were included for analysis. The SUV was significantly higher in patients with second primary cancer than in those with metastatic disease (58 vs 28%, respectively, p < 0.001). The area under the ROC curve was 0.81 and the odds ratio for the optimal cut-off was 18.4. CONCLUSION: SUVs from (18)F-FDG PET images can be helpful in differentiating metastatic disease from second primary tumours in patients with synchronous pulmonary lesions. Further studies are warranted to confirm the consistency of these results.1 november 201

Species-area relationships are modulated by trophic rank, habitat affinity, and dispersal ability

Contains fulltext : 140052.pdf (publisher's version ) (Open Access

Evolution of predator dispersal in relation to spatio-temporal prey dynamics : how not to get stuck in the wrong place!

Peer reviewedPublisher PD

XM02 is superior to placebo and equivalent to Neupogen™ in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy

Abstract Background Recombinant granulocyte colony-stimulating factors (G-CSFs) such as Filgrastim are used to treat chemotherapy-induced neutropenia. We investigated a new G-CSF, XM02, and compared it to Neupogen™ after myelotoxic chemotherapy in breast cancer (BC) patients. Methods A total of 348 patients with BC receiving docetaxel/doxorubicin chemotherapy were randomised to treatment with daily injections (subcutaneous 5 μg/kg/day) for at least 5 days and a maximum of 14 days in each cycle of XM02 (n = 140), Neupogen™ (n = 136) or placebo (n = 72). The primary endpoint was the duration of severe neutropenia (DSN) in cycle 1. Results The mean DSN in cycle 1 was 1.1, 1.1, and 3.9 days in the XM02, Neupogen™, and placebo group, respectively. Superiority of XM02 over placebo and equivalence of XM02 with Neupogen™ could be demonstrated. Toxicities were similar between XM02 and Neupogen™. Conclusion XM02 was superior to placebo and equivalent to Neupogen™ in reducing DSN after myelotoxic chemotherapy. Trial Registration Current Controlled Trials ISRCTN02270769</p

A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours

Contains fulltext : 89517timmer-bonte.pdf (publisher's version ) (Closed access)BACKGROUND: This Phase Ib dose-escalating study investigated safety, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and clinical antitumour activity of tosedostat (CHR-2797), an orally bioavailable aminopeptidase inhibitor, in combination with paclitaxel. METHODS: A total of 22 patients received paclitaxel (135-175 mg m(-2)) intravenously, administered once every three weeks for up to six cycles, with oral tosedostat (90-240 mg) daily. RESULTS: One DLT (grade 3 dyspnoea) was observed in one patient with tosedostat 180 mg combined with paclitaxel 175 mg m(-2). A high number of paclitaxel infusion reactions was noted during the second administration (59%) and this prompted interruption of tosedostat dosing for 5 days around every second and subsequent paclitaxel infusion. No formal MTD was determined because of the high frequency of paclitaxel infusion reactions that may have been influenced by tosedostat. Most frequently observed drug-related adverse events were alopecia, fatigue (95% each), peripheral sensory neuropathy (59%), paclitaxel hypersensitivity (59%) and rash (55%). One patient died because of eosinophilic myocarditis, possibly related to study medication. There was no PK interaction between tosedostat and paclitaxel. In all, 3 patients had a partial response and 12 patients had stable disease lasting >3 months. CONCLUSION: The combination of tosedostat with paclitaxel was well tolerated except for the high incidence of paclitaxel-related infusion reactions

Phase Ib study of NGR–hTNF, a selective vascular targeting agent, administered at low doses in combination with doxorubicin to patients with advanced solid tumours

Contains fulltext : 81937timmer-bonte.pdf (publisher's version ) (Closed access)BACKGROUND: Asparagine-glycine-arginine-human tumour necrosis factor (NGR-hTNF) is a vascular targeting agent exploiting a tumour-homing peptide (NGR) that selectively binds to aminopeptidase N/CD13, overexpressed on tumour blood vessels. Significant preclinical synergy was shown between low doses of NGR-TNF and doxorubicin. METHODS: The primary aim of this phase I trial was to verify the safety of low-dose NGR-hTNF combined with doxorubicin in treating refractory/resistant solid tumours. Secondary objectives included pharmacokinetics (PKs), pharmacodynamics, and clinical activity. In all 15 patients received NGR-hTNF (0.2-0.4-0.8-1.6 microg m(-2)) and doxorubicin (60-75 mg m(-2)), both given intravenously every 3 weeks. RESULTS: No dose-limiting toxicity occurred and the combination was well tolerated. Around two cases of neutropenic fevers, lasting 2 days, and two cases of cardiac ejection-fraction drops, one asymptomatic and the other symptomatic, were registered. Only 11% of the adverse events were related to NGR-hTNF and were short-lasting and mild-to-moderate in severity. There was no apparent PK interaction and the shedding of soluble TNF-receptors did not increase to 0.8 microg m(-2). One partial response (7%), at dose level 0.8 microg m(-2), and 10 stable diseases (66%), lasting for a median duration of 5.6 months, were observed. CONCLUSIONS: NGR-hTNF plus doxorubicin was administered safely and showed promising activity in patients pre-treated with anthracyclines. The dose level of 0.8 microg m(-2) NGR-hTNF plus doxorubicin 75 mg m(-2) was selected for phase II development

Rituximab in early systemic sclerosis

Objectives (1) Hypothesis testing of the potency of rituximab (RTX) in preventing fibrotic complications and (2) assessing acceptability and feasibility of RTX in early systemic sclerosis (SSc). Methods A small, 24-month, randomised, double-blind, placebo-controlled, single-centre trial in patients with SSc diagnosed <2 years was conducted. Patients received RTX or placebo infusions at t=0, t=15 days and t=6 months. Patients were clinically evaluated every 3 months, with lung function tests and high-resolution CT every other visit. Skin biopsies were taken at baseline and month 3. Immunophenotyping of peripheral blood mononuclear cells was performed at every visit, except at months 9 and 18. Adverse events, course of skin and pulmonary involvement and B cell populations in skin and peripheral blood were evaluated. Results In total 16, patients (rituximab n=8, placebo n=8) were included. Twelve patients had diffuse cutaneous SS