Doing confirmation with ja/nee hoor. Sequential and prosodic characteristics of a Dutch discourse particle

This paper offers sequential-interactional and prosodic observations on the confirmation forms ja hoor / nee hoor ('yes'+particle hoor / 'no' + hoor) in Dutch talk-in-interaction, as part of a larger analysis of the form and function of the particle hoor. We show that ja/nee hoor is used as a marked confirmation in sequentially specifiable context-types. When used as a response to queries, the speaker marks doing confirmation as programmatically motivated. When used in environments that further §[ sequence expansion], ja/nee hoor resists such expansion. Thus, the use of ja/nee hoor is motivated by an orientation to multiple levels of discourse organization. Ja/nee hoor is associated with recurrent pitch contours which are systematically distributed across environments of use. We discuss our findings in relation to previous findings on the use of hoor in Dutch

Phonological complexity, segment rate and speech tempo perception

Studies of speech tempo commonly use syllable or segment rate as a proxy measure for perceived tempo. In languages whose phonologies allow substantial syllable complexity these measures can produce figures on quite different scales; however, little is known about the correlation between syllable and segment rate measurements on the one hand and naïve listeners’ tempo judgements on the other. We follow up on the findings of one relevant study on German [1], which suggest that listeners attend to both syllable and segment rates in making tempo estimates, through a weighted average of the rates in which syllable rate carries more weight. We report on an experiment in which we manipulate phonological complexity in English utterance pairs that are constant in syllable rate. Listeners decide for each pair which utterance sounds faster. Our results suggest that differences in segment rate that do not correspond to differences in syllable rate have little impact on perceived speech tempo in English

Cost-effectiveness of enzyme replacement therapy with alglucosidase alfa in classic-infantile patients with Pompe disease

Background: Infantile Pompe disease is a rare metabolic disease. Patients generally do not survive the first year of life. Enzyme replacement therapy (ERT) has proven to have substantial effects on survival in infantile Pompe disease. However, the costs of therapy are very high. In this paper, we assess the cost-effectiveness of enzyme replacement therapy in infantile Pompe disease. Methods. A patient simulation model was used to compare costs and effects of ERT with costs of effects of supportive therapy (ST). The model was filled with data on survival, quality of life and costs. For both arms of the model, data on survival w

Listeners’ sensitivity to syllable complexity in spontaneous speech tempo perception

Studies of speech tempo commonly use syllable or segment rate as a proxy measure for perceived tempo. While listeners’ sensitivity to syllable rate is well-established [1-4], evidence for listeners’ additional sensitivity to segment rate--that is, to syllable complexity alongside syllable rate--is as yet lacking. In [5, 6] we reported experiments that yielded no evidence for listeners’ orientation to segment rate differences between stimuli that have the same syllable rate. In these experiments, we kept syllable rate constant by equalizing phrase durations. As phrase duration is a separate temporal parameter from syllable rate, we must complement this work with experiments using less homogeneous stimulus sets. In this paper we report on an experiment that uses stimuli selected from a corpus of spontaneous British English speech. Within crucial subsets there was minimal variation in one out of syllable and segment rate, and substantial variation in the other. Stimulus duration varied independently. Listeners ranked stimuli for perceived tempo. Results suggest that faced with these more variable stimuli, listeners do orient to segment rate in ranking stimuli that have near-identical syllable rates--presumably reflecting the influence of syllable complexity. Moreover, stimulus duration emerges as a separate factor influencing listeners’ rankings, alongside f0 and intensity

Classic infantile Pompe patients approaching adulthood: A cohort study on consequences for the brain

Aim: To examine the long-term consequences of glycogen storage in the central nervous system (CNS) for classic infantile Pompe disease using enzyme replacement therapy. Method: Using neuropsychological tests and brain magnetic resonance imaging (MRI), we prospectively assessed a cohort of 11 classic infantile Pompe patients aged up to 17 years. Results: From approximately age 2 years onwards, brain MRI showed involvement of the periventricular white matter and centrum semiovale. After 8 years of age, additional white-matter abnormalities occurred in the corpus callosum, internal and external capsule, and subcortical areas. From 11 years of age, white-matter abnormalities were also found in the brainstem. Although there seemed to be a characteristic pattern of involvement over time, there were considerable variations between patients, reflected by variations in neuropsychological development. Cognitive development ranged from stable and normal to declines that lead to intellectual disabilities. Interpretation: As treatment enables patients with classic infantile Pompe disease to reach adulthood, white-matter abnormalities are becoming increasingly evident, affecting the neuropsychological development. Therefore, we advise follow-up programs are expanded to capture CNS involvement in larger, international patient cohorts, to incorporate our findings in the counselling of parents before the start of treatment, and to include the brain as an additional target in the development of next-generation therapeutic strategies for classic infantile Pompe disease. What this paper adds: In our long-term survivors treated intravenously with enzyme replacement therapy, we found slowly progressive symmetric white-matter abnormalities. Cognitive development varied from stable and normal to declines towards intellectual disabilities

Informativeness, Timing and Tempo in Lexical Self-Repair

This paper presents a study of the temporal organization of lexical repair in spontaneous Dutch speech. It assesses the extent to which offset-to-repair duration and repair tempo can be predicted on the basis of offset timing, reparandum tempo and measures of the informativeness of the crucial lexical items in the repair. Specifically, we address the expectations that repairs that are initiated relatively early are produced relatively fast throughout, and that relatively highly informative repairs are produced relatively slowly. For informativeness, we implement measures based on repair semantics, lexical frequency counts and cloze probabilities. Our results highlight differences between factual and linguistic error repairs, which have not been consistently distinguished in previous studies, and provide some evidence to support the notion that repairs that are initiated relatively early are produced relatively fast. They confirm that lexical frequency counts are rough measures of contextual predictability at best, and reveal very few significant effects of our informativeness measures on the temporal organization of lexical self-repair. Moreover, although we can confirm that most repairs have a repair portion that is fast relative to its reparandum, this cannot be attributed to the relative informativeness of the two portions. Our findings inform the current debate on the division of labour between inner and overt speech monitoring, and suggest that, although the influence of informativeness on speech production is extensive, it is not ubiquitous

On tempo in dispreferred turns: A recurrent pattern in a Dutch corpus

Purpose: This paper addresses the question as to whether dispreferred response turns in spoken interaction have recurrent prosodic characteristics. Following observations on the phonetics of dispreferred turns found in the literature, the paper focuses on the temporal organisation of dispreferred turns. In particular, it investigates whether the tempo of dispreferred turns correlates with the tempo of the immediately prior turns to which they respond. Methodology: The paper focuses on a collection of dispreferred turns taken from a corpus of Dutch conversation. Dispreferred turns are identified and analysed structurally and pragmatically using the methods of Conversation Analysis. Relevant components are subjected to temporal phonetic analysis, and patterns are quantified where possible. Findings: The paper suggests that dispreferred turns of the type considered are consistently paced relative to their prior turns. In particular, the turn component thatmost clearly implements the dispreferred action is, in a majority of cases, slow relative to the turn to which it responds. While dispreferred turns without this characteristic are found, the paper suggests that these may be oriented to as unusual or problematic by participants in the interaction. Value: The paper increases our understanding of the organisation of dispreferred turns, which continue to attract debate in the conversation-analytic literature, and, more generally, of the systematic use of prosodic resources by participants in spoken interaction

Long-term cognitive follow-up in children treated for Maroteaux-Lamy syndrome

Background: It remains unclear to what extent the brain is affected by Maroteaux-Lamy syndrome (MPS VI), a progressive lysosomal storage disorder. While enzyme replacement therapy (ERT) elicits positive effects, the drug cannot cross the blood–brain barrier. We therefore studied cognitive development and brain abnormalities in the Dutch MPS VI patient population treated with ERT. Methods: In a series of 11 children with MPS VI (age 2 to 20 years), we assessed cognitive functioning and brain magnetic resonance imaging prospectively at the start of ERT and at regular times thereafter up to 4.8 years. We also assessed the children’s clinical characteristics, their siblings’ cognitive development, and their parents’ educational levels. Results: The patients’ intelligence scores ranged from normal to mentally delayed (range test scores 52–131). In 90 %, their scores remained fairly stable during follow-up, generally lying in the same range as their siblings’ test scores (median for patients = 104, median for siblings = 88) and comparing well with the parental educational levels. Native-speaking patients had higher intelligence test scores than non-native-speaking patients. Two patients, both with high baseline glycosaminoglycan levels in their urine and severe mutations in the arylsulfatase B gene, scored clearly lower than expected. Patients with pY210C performed best. Brain abnormalities were aspecific, occurring more in patients with severe symptoms. Conclusion: Our study shows that cognitive development in MPS VI patients is determined not only by familial and social-background factors, but, in patients with a severe form of the disease, also by the disease itself. Therefore in patients with severe disease presentation cognition should be monitored carefully

Mucopolysaccharidosis type VI phenotypes-genotypes and antibody response to galsulfase

Background: Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome; MPS VI) is an autosomal recessive lysosomal storage disorder in which deficiency of N-acetylgalactosamine 4-sulfatase (arylsulfatase B; ARSB) leads to the storage of glycosaminoglycans (GAGs) in connective tissue. The genotype-phenotype correlation has been addressed in several publications but the picture is not complete. Since 2007, enzyme-replacement therapy (ERT) has been available for patients with MPS VI in the Netherlands. The purpose of our study was to learn more about the genotype-phenotype correlations in MPS VI and the antibody response to ERT with galsulfase (recombinant human arylsulfatase B). Methods. We identified ARSB mutations in 12 patients and used site-directed mutagenesis to study their effect. Antibody levels to galsulfase were measured using ELISA and a semi-quantitative immunoprecipitation method. We assessed the in vitro inhibitory effect of antibodies on galsulfase uptake and their effect on clinical outcome. Results: Five patients had a rapidly progressive phenotype and seven a slowly progressive phenotype. In total 9 pathogenic mutations were identified including 4 novel mutations (N301K, V332G, A237D, and c.1142 + 2 T > C) together composing 8 pathogenic genotypes. Most mutations appeared not to affect the synthesis of ARSB (66 kD precursor), but to hamper its maturation (43 kD ARSB). Disease severity was correlated with urinary GAG excretion. All patients developed antibodies to galsulfase within 26 weeks of treatment. It was demonstrated that these antibodies can inhibit the uptake of galsulfase in vitro. Conclusions: The clinical phenotypes and the observed defects in the biosynthesis of ARSB show that some of the mutations that we identified are clearly more severe than others. Patients receiving galsulfase as enzyme-replacement therapy can develop antibodies towards the therapeutic protein. Though most titers are modest, they can exceed a level at which they potentially affect the clinical outcome of enzyme-replacement therapy

EXPRESS: Testing for canonical form orientation in speech tempo perception.

We report on two experiments that aimed to test the hypothesis that English listeners orient to full pronunciation forms-'canonical forms'-in judging the tempo of speech that features deletions. If listeners orient to canonical forms, this should mean that the perceived tempo of speech containing deletions is high relative to the speech's articulation rate calculated on the basis of surface phone strings. We used controlled stimuli to test this hypothesis. We created sentences with one ambiguous word form (for example, support~sport), to give half of the listeners an orthographic form that includes support and the other half an otherwise identical orthographic form with sport. In both experiments listeners judged the tempo of the sentences, which allowed us to assess whether the difference in imposed interpretation had an impact on perceived tempo. Experiment 1 used a tempo rating task in which listeners evaluated the tempo of experimental stimuli relative to comparison stimuli, on a continuous scale. Experiment 2 used a tempo comparison task in which listeners judged whether second members of stimulus pairs were slower or faster than first members. Both experiments revealed the predicted effect of the imposed word interpretation: sentences with an imposed 'schwa' interpretation for the ambiguous word form were judged faster than (the same) sentences with an imposed 'no schwa' interpretation. However, in both experiments the effect was small and variables related to the experimental design had significant effects on responses. We discuss the results' implications for our understanding of speech tempo perception