Lexicality and frequency in specific language impairment: accuracy and error data from two nonword repetition tests

Purpose: Deficits in phonological working memory and deficits in phonological processing have both been considered potential explanatory factors in Specific Language Impairment (SLI). Manipulations of the lexicality and phonotactic frequency of nonwords enable contrasting predictions to be derived from these hypotheses. Method: 18 typically developing (TD) children and 18 children with SLI completed an assessment battery that included tests of language ability, non-verbal intelligence, and two nonword repetition tests that varied in lexicality and frequency. Results: Repetition accuracy showed that children with SLI were unimpaired for short and simple high lexicality nonwords, whereas clear impairments were shown for all low lexicality nonwords. For low lexicality nonwords, greater repetition accuracy was seen for nonwords constructed from high over low frequency phoneme sequences. Children with SLI made the same proportion of errors that substituted a nonsense syllable for a lexical item as TD children, and this was stable across nonword length. Conclusions: The data show support for a phonological processing deficit in children with SLI, where long-term lexical and sub-lexical phonological knowledge mediate the interpretation of nonwords. However, the data also suggest that while phonological processing may provide a key explanation of SLI, a full account is likely to be multi-faceted

Someone is pulling the strings: hypersensitive agency detection and belief in conspiracy theories

We hypothesized that belief in conspiracy theories would be predicted by the general tendency to attribute agency and intentionality where it is unlikely to exist. We further hypothesized that this tendency would explain the relationship between education level and belief in conspiracy theories, where lower levels of education have been found to be associated with higher conspiracy belief. In Study 1 (N=202) participants were more likely to agree with a range of conspiracy theories if they also tended to attribute intentionality and agency to inanimate objects. As predicted, this relationship accounted for the link between education level and belief in conspiracy theories. We replicated this finding in Study 2 (N=330), whilst taking into account beliefs in paranormal phenomena. These results suggest that education may undermine the reasoning processes and assumptions that are reflected in conspiracy belief

3-({[(1-Phenyl­eth­yl)sulfan­yl]methane­thio­yl}sulfan­yl)propanoic acid

In the title compound, C12H14O2S3, a chain transfer agent (CTA) used in polymerization, the dihedral angle between the aromatic ring and the CS3 grouping is 84.20 (10)°. In the crystal, carb­oxy­lic acid inversion dimers linked by pairs of O—H⋯O hydrogen bonds generate R 2 2(8) loops

Forest Fires Across Italian Regions and Implications for Climate Change: A Panel Data Analysis

In this paper, we analyze the determinants of monthly variations in forest fire frequency and on the size of the area burnt for Italian regions between 2000 and 2011. We employ panel data techniques, which allow capturing the dynamics of fire danger due to changes in past climatic conditions, after accounting for regional fixed effects to control region-specific unobserved and time-invariant factors. Results highlight a significant heterogeneity of the effects of driving factors across the Italian peninsula and weather seasons. Climatic conditions also show lasting effects within the year. Using climate change projections for 2016–2035, we then obtain the projected forest fire frequency and total area burnt across the Italian peninsula for the same period. Climate change is expected to increase the number of forest fires across the whole peninsula, which is more evident for the central part of Italy. Even though most of annual increases in fire events relate to the summer period, intensifications in frequency during autumn become more evident in the southern Italy. We extend finally our analysis to investigate the contribution of socio-economic factors to fire regime and the role of education and the containment of fraudulent activity is also highlighted.</p

Mechanical behaviour and rupture of normal and pathological human ascending aortic wall

The mechanical properties of aortic wall, both healthy and pathological, are needed in order to develop and improve diagnostic and interventional criteria, and for the development of mechanical models to assess arterial integrity. This study focuses on the mechanical behaviour and rupture conditions of the human ascending aorta and its relationship with age and pathologies. Fresh ascending aortic specimens harvested from 23 healthy donors, 12 patients with bicuspid aortic valve (BAV) and 14 with aneurysm were tensile-tested in vitro under physiological conditions. Tensile strength, stretch at failure and elbow stress were measured. The obtained results showed that age causes a major reduction in the mechanical parameters of healthy ascending aortic tissue, and that no significant differences are found between the mechanical strength of aneurysmal or BAV aortic specimens and the corresponding age-matched control group. The physiological level of the stress in the circumferential direction was also computed to assess the physiological operation range of healthy and diseased ascending aortas. The mean physiological wall stress acting on pathologic aortas was found to be far from rupture, with factors of safety (defined as the ratio of tensile strength to the mean wall stress) larger than six. In contrast, the physiological operation of pathologic vessels lays in the stiff part of the response curve, losing part of its function of damping the pressure waves from the heart

The time course of auditory and language-specific mechanisms in compensation for sibilant assimilation

Models of spoken-word recognition differ on whether compensation for assimilation is language-specific or depends on general auditory processing. English and French participants were taught words that began or ended with the sibilants /s/ and /∫/. Both languages exhibit some assimilation in sibilant sequences (e.g., /s/ becomes like [∫] in dress shop and classe chargée), but they differ in the strength and predominance of anticipatory versus carryover assimilation. After training, participants were presented with novel words embedded in sentences, some of which contained an assimilatory context either preceding or following. A continuum of target sounds ranging from [s] to [∫] was spliced into the novel words, representing a range of possible assimilation strengths. Listeners' perceptions were examined using a visual-world eyetracking paradigm in which the listener clicked on pictures matching the novel words. We found two distinct language-general context effects: a contrastive effect when the assimilating context preceded the target, and flattening of the sibilant categorization function (increased ambiguity) when the assimilating context followed. Furthermore, we found that English but not French listeners were able to resolve the ambiguity created by the following assimilatory context, consistent with their greater experience with assimilation in this context. The combination of these mechanisms allows listeners to deal flexibly with variability in speech forms

New Towns Heritage Research Network

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Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.  Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.  Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.  Conclusion: Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

ADVANCE-TBI study protocol: traumatic brain injury outcomes in UK military personnel serving in Afghanistan between 2003 and 2014 - a longitudinal cohort study

INTRODUCTION: Outcomes of traumatic brain injury (TBI) are highly variable, with cognitive and psychiatric problems often present in survivors, including an increased dementia risk in the long term. Military personnel are at an increased occupational risk of TBI, with high rates of complex polytrauma including TBI characterising the UK campaign in Afghanistan. The ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE)-TBI substudy will describe the patterns, associations and long-term outcomes of TBI in the established ADVANCE cohort. METHODS AND ANALYSIS: The ADVANCE cohort comprises 579 military personnel exposed to major battlefield trauma requiring medical evacuation, and 566 matched military personnel without major trauma. TBI exposure has been captured at baseline using a standardised interview and registry data, and will be refined at first follow-up visit with the Ohio State Method TBI interview (a National Institute of Neurological Disorders and Stroke TBI common data element). Participants will undergo blood sampling, MRI and detailed neuropsychological assessment longitudinally as part of their follow-up visits every 3-5 years over a 20-year period. Biomarkers of injury, neuroinflammation and degeneration will be quantified in blood, and polygenic risk scores calculated for neurodegeneration. Age-matched healthy volunteers will be recruited as controls for MRI analyses. We will describe TBI exposure across the cohort, and consider any relationship with advanced biomarkers of injury and clinical outcomes including cognitive performance, neuropsychiatric symptom burden and function. The influence of genotype will be assessed. This research will explore the relationship between military head injury exposure and long-term outcomes, providing insights into underlying disease mechanisms and informing prevention interventions. ETHICS AND DISSEMINATION: The ADVANCE-TBI substudy has received a favourable opinion from the Ministry of Defence Research Ethics Committee (ref: 2126/MODREC/22). Findings will be disseminated via publications in peer-reviewed journals and presentations at conferences