Investigating the role of Copy Number Variants in Specific Language Impairment and identification of new candidate genes

Specific language impairment (SLI) is a complex neurodevelopmental disorder defined as an unexpected failure to develop normal language abilities for no obvious reason. Copy number variants (CNVs) are an important source of variation in the susceptibility to neuropsychiatric disorders. Therefore, a CNV study within SLI families was performed to investigate the role of structural variants in SLI. Among the identified CNVs, we focused on CNVs on chromosome 15q11-q13, recurrently observed in neuropsychiatric conditions, and a homozygous exonic microdeletion in ZNF277. Since this microdeletion falls within the AUTS1 locus, a region linked to autism spectrum disorders (ASD), we investigated a potential role of ZNF277 in SLI and ASD. Frequency data and expression analysis of the ZNF277 microdeletion suggested that this variant may contribute to the risk of language impairments in a complex manner, that is independent of the autism risk previously described in this region. Moreover, we identified an affected individual with a dihydropyrimidine dehydrogenase (DPD) deficiency, caused by compound heterozygosity of two deleterious variants in the gene DPYD. Since DPYD represents a good candidate gene for both SLI and ASD, we investigated its involvement in the susceptibility to these two disorders, focusing on the splicing variant rs3918290, the most common mutation in the DPD deficiency. We observed a higher frequency of rs3918290 in SLI cases (1.2%), compared to controls (~0.6%), while no difference was observed in a large ASD cohort. DPYD mutation screening in 4 SLI and 7 ASD families carrying the splicing variant identified six known missense changes and a novel variant in the promoter region. These data suggest that the combined effect of the mutations identified in affected individuals may lead to an altered DPD activity and that rare variants in DPYD might contribute to a minority of cases, in conjunction with other genetic or non-genetic factors.

Plato's Doctrine Of Forms: Modern Misunderstandings

Among the philosophical ideas of Plato, perhaps the most famous is his doctrine of forms. This doctrine has faced harsh criticism due, in large part, to the interpretations of this position by modern philosophers such as René Descartes, John Locke, and Immanuel Kant. For example, Plato has been interpreted as presenting a ¿two-worlds¿ approach to form and thing and as advancing a rationalist approach to epistemology. His forms have often been interpreted as ideas and as perfect copies of the things of the visible world. In this thesis, I argue that these, along with other interpretations of Plato presented by the moderns, are based on misunderstandings of Plato¿s overall philosophy. In so doing, I attempt to show that the doctrine of forms cannot be directly interpreted into the language of Cartesian, Lockean, and Kantian metaphysics and epistemology, and thus should not be prematurely dismissed because of these modern Platonic interpretations. By analyzing the Platonic dialogues beside the writings of the modern philosophers, I conclude that three of the most prominent modern philosophers, as representatives of their respective philosophical frameworks, have fundamentally misunderstood the nature of Plato¿s famous doctrine of forms. This could have significant implications for the future of metaphysics and epistemology by providing an interpretation of Plato which adds to, instead of contradicts, the developments of modern philosophy.

Phonetic Aspects of Speech Communication

Nadeina set out to develop methods of speech development in Russian as a mother tongue, focusing on improving diction, training in voice quality control, intonation control, the removal of dialect, and speech etiquette. She began with training in the receptive skills of language, i.e. reading and listening, since the interpretation of someone else's language plays an important role in language production. Her studies of students' reading speed of students showed that it varies between 40 and 120 words per minute, which is normally considered very slow. She discovered a strong correlation between speed of reading and speaking skills: the slower a person reads the worse is their ability to speak and has designed exercises to improve reading skills. Nadeina also believes that listening to other people's speech is very important, both to analyse its content and in some cases as an example, so listening skills need to be developed. Many people have poor pronunciation habits acquired as children. On the basis of speech samples from young Russians (male and female, aged 17-22), Nadeina analysed the commonest speech faults - nasalisation, hesitation and hemming at the end of sense-groups, etc. Using a group of twenty listeners, she looked for a correlation between how voice quality is perceived and certain voice quality parameters, e.g. pitch range, tremulousness, fluency, whispering, harshness, sonority, tension and audible breath. She found that the less non-linguistic segment variations in speech appeared, the more attractive the speech was rated. The results are included in a textbook aimed at helping people to improve their oral skills and to communicate ideas to an audience. She believes this will assist Russian officials in their attempts to communicate their ideas to different social spheres, and also foreigners learning Russian.

Meta-analysis: chondroitin for osteoarthritis of the knee or hip

BACKGROUND: Previous meta-analyses described moderate to large benefits of chondroitin in patients with osteoarthritis. However, recent large-scale trials did not find evidence of an effect. PURPOSE: To determine the effects of chondroitin on pain in patients with osteoarthritis. DATA SOURCES: The authors searched the Cochrane Central Register of Controlled Trials (1970 to 2006), MEDLINE (1966 to 2006), EMBASE (1980 to 2006), CINAHL (1970 to 2006), and conference proceedings; checked reference lists; and contacted authors. The last update of searches was performed on 30 November 2006. STUDY SELECTION: Studies were included if they were randomized or quasi-randomized, controlled trials that compared chondroitin with placebo or with no treatment in patients with osteoarthritis of the knee or hip. There were no language restrictions. DATA EXTRACTION: The authors extracted data in duplicate. Effect sizes were calculated from the differences in means of pain-related outcomes between treatment and control groups at the end of the trial, divided by the pooled SD. Trials were combined by using random-effects meta-analysis. DATA SYNTHESIS: 20 trials (3846 patients) contributed to the meta-analysis, which revealed a high degree of heterogeneity among the trials (I2 = 92%). Small trials, trials with unclear concealment of allocation, and trials that were not analyzed according to the intention-to-treat principle showed larger effects in favor of chondroitin than did the remaining trials. When the authors restricted the analysis to the 3 trials with large sample sizes and an intention-to-treat analysis, 40% of patients were included. This resulted in an effect size of -0.03 (95% CI, -0.13 to 0.07; I2 = 0%) and corresponded to a difference of 0.6 mm on a 10-cm visual analogue scale. A meta-analysis of 12 trials showed a pooled relative risk of 0.99 (CI, 0.76 to 1.31) for any adverse event. LIMITATIONS: For 9 trials, the authors had to use approximations to calculate effect sizes. Trial quality was generally low, heterogeneity among the trials made initial interpretation of results difficult, and exploring sources of heterogeneity in meta-regression and stratified analyses may be unreliable. CONCLUSIONS: Large-scale, methodologically sound trials indicate that the symptomatic benefit of chondroitin is minimal or nonexistent. Use of chondroitin in routine clinical practice should therefore be discouraged.

Tree phenology and carbon dioxide fluxes - use of digital photography for process-based interpretation at the ecosystem scale

Vegetation phenology is an important indicator of climate change and climate variability and it is strongly connected to biospheric–atmospheric gas exchange. We aimed to evaluate the applicability of phenological information derived from digital imagery for the interpretation of CO2 exchange measurements. For the years 2005–2007 we analyzed seasonal phenological development of 2 temperate mixed forests using tower-based imagery from standard RGB cameras. Phenological information was jointly analyzed with gross primary productivity (GPP) derived from net ecosystem exchange data. Automated image analysis provided reliable information on vegetation developmental stages of beech and ash trees covering all seasons. A phenological index derived from image color values was strongly correlated with GPP, with a significant mean time lag of several days for ash trees and several weeks for beech trees in early summer (May to mid-July). Leaf emergence dates for the dominant tree species partly explained temporal behaviour of spring GPP but were also masked by local meteorological conditions. We conclude that digital cameras at flux measurement sites not only provide an objective measure of the physiological state of a forest canopy at high temporal and spatial resolutions, but also complement CO2 and water exchange measurements, improving our knowledge of ecosystem processes.

Education and Ideologies of the Knowledge Economy: Europe and the Politics of Emulation

The Austrian philosopher Ludwig Wittgenstein famously proposed a style of philosophy that was directed against certain pictures [bild] that tacitly direct our language and forms of life. His aim was to show the fly the way out of the fly bottle and to fight against the bewitchment of our intelligence by means of language: “A picture held us captive. And we could not get outside it, for it lay in our language and language seemed to repeat it to us inexorably” (Wittgenstein 1953, 115). In this context Wittgenstein is talking of philosophical pictures, deep metaphors that have structured our language but he does also use the term picture in other contexts (see Owen 2003, 83). I want to appeal to Wittgenstein in my use of the term ideology to refer to the way in which powerful underlying metaphors in neoclassical economics have a strong rhetorical and constitutive force at the level of public policy. Indeed, I am specifically speaking of the notion of ‘the performative’ in Wittgenstein and Austin. The notion of the knowledge economy has a prehistory in Hayek (1937; 1945) who founded the economics of knowledge in the 1930s, in Machlup (1962; 1970), who mapped the emerging employment shift to the US service economy in the early 1960s, and to sociologists Bell (1973) and Touraine (1974) who began to tease out the consequences of these changes for social structure in the post-industrial society in the early 1970s. The term has been taken up since by economists, sociologists, futurists and policy experts recently to explain the transition to the so-called ‘new economy’. It is not just a matter of noting these discursive strands in the genealogy of the ‘knowledge economy’ and related or cognate terms. We can also make a number of observations on the basis of this brief analysis. First, there has been a succession of terms like ‘postindustrial economy’, ‘information economy’, ‘knowledge economy’, ‘learning economy’, each with a set of related concepts emphasising its social, political, management or educational aspects. Often these literatures are not cross-threading and tend to focus on only one aspect of phenomena leading to classic dichotomies such as that between economy and society, knowledge and information. Second, these terms and their family concepts are discursive, historical and ideological products in the sense that they create their own meanings and often lead to constitutive effects at the level of policy. Third, while there is some empirical evidence to support claims concerning these terms, at the level of public policy these claims are empirically underdetermined and contain an integrating, visionary or futures component, which necessarily remains untested and is, perhaps, in principle untestable.

Manner of Obtainment as a relative in a family of resultative constructions

The present paper examines the syntactic and semantic properties of a group of constructions which carry an idiomatic interpretation of obtainment. In Polish and German, the constructions under consideration consist of a verb with a directional particle followed by an object NP, as exemplified in (1a)-(1b). (1a) Adam wynurkował starego buta. (Polish) Adam wy- snorkeled old shoe. ‘Adam found an old shoe while snorkeling.’ (1b) Michael erboxte sich den Titel. (German) Michael er- boxed REFL the title. ‘Michael boxed his way to the (championship) title.’ Sentences containing these constructions will be assumed to have the same basic interpretation “Subject obtains/produces Object by V-ing”. A constructional analysis of the constructions will be proposed, as they pose licensing problems and their interpretation cannot be accounted for in terms of the individual conceptual structures of the lexical items composing the sentence. Unlike most accounts of verb particle constructions based on implicit or explicit assumptions of straightforward semantic composition, the present study proposes an analysis under which the semantic structure of verb particle combinations is not a compositional function of the verb and the particle/prefix alone. It is argued that the construction comes with its own subcategorization frame (separate from that carried by the verb) which is motivated by the meaning of the construction and its corresponding constructional subevent. Additionally, a crosslinguistic correlation will be shown to hold between a language’s ability to express event conflation (Talmy 1985, 2000) and the occurrence of some form of the construction in that language. This will be taken as an indication of the resultative nature of those types of directional phrases which involve the semantic interpretation of boundary crossing.

Review of "Lingua e diritto. Livelli di analisi"

The book Lingua e diritto: Livelli di analisi brings together contributions by scholars from different fields: anthropology, theory and philosophy of law, comparative law, European law, translation, discourse analysis, pragmatics, morpho-syntax and cognitive linguistics. Contributions deal with a number of issues situated at the interface between language and law: questions of meaning and the interpretation of legal texts, the nature of legal interpretation, problems of ambiguity and vagueness in legal texts, the characteristics of legal language, legal terminology and the multilingualism of European law. As a whole, the book provides insights into a number of different topics and perspectives situated at the interface between language and law. It is of interest both to lawyers and linguists as a valuable and very welcome contribution to the field of legal linguistics.

XSAMPL3D: An Action Description Language for the Animation of Virtual Characters

In this paper we present XSAMPL3D, a novel language for the high-level representation of actions performed on objects by (virtual) humans. XSAMPL3D was designed to serve as action representation language in an imitation-based approach to character animation: First, a human demonstrates a sequence of object manipulations in an immersive Virtual Reality (VR) environment. From this demonstration, an XSAMPL3D description is automatically derived that represents the actions in terms of high-level action types and involved objects. The XSAMPL3D action description can then be used for the synthesis of animations where virtual humans of different body sizes and proportions reproduce the demonstrated action. Actions are encoded in a compact and human-readable XML-format. Thus, XSAMPL3D describtions are also amenable to manual authoring, e.g. for rapid prototyping of animations when no immersive VR environment is at the animator's disposal. However, when XSAMPL3D descriptions are derived from VR interactions, they can accomodate many details of the demonstrated action, such as motion trajectiories,hand shapes and other hand-object relations during grasping. Such detail would be hard to specify with manual motion authoring techniques only. Through the inclusion of language features that allow the representation of all relevant aspects of demonstrated object manipulations, XSAMPL3D is a suitable action representation language for the imitation-based approach to character animation.

Legal Translation and the Bilingual Publication of Roman Imperial Constitutions

The present paper aims at investigating translation techniques and publication methods of Roman imperial constitutions published in Greek in the eastern provinces of the empire, where the official Latin was not well-established. Language, being a tool for normative communication must be comprehensible to the addressees of the norm, therefore publication of a normative text in a multilingual society brings along difficulties related in particular to the translatability of legal terminology. Language problems appear, however, not only in the level of communication, but also in those of implementation and interpretation of norms. Linguistic diversity, which currently afflicts legislators in the EU, has already been a challenge for the legislators in the Roman Empire. Major difficulty was the necessity of expressing Roman legal concepts in Greek language. Centralized translation system and consequent use of terminology helped to adapt Greek for the purposes of Roman legislator creating new technical vocabulary.

Plurilingual Interpretation in WTO Panel and Appellate Body Reports

This article analyzes the extent to which the Appellate Body and WTO panels compare the authentic texts in their examination of the WTO Agreements and the extent to which the parties themselves do so in their arguments. The texts of the WTO Agreements are authentic in English, French and Spanish. Article 33 of the Vienna Convention on the Law of Treaties governs the interpretation of treaties authenticated in two or more languages. WTO practice diverges significantly from the rules set out in Article 33 and the travaux préparatoires of the International Law Commission. The terms of a plurilingual treaty are presumed to have the same meaning in each authentic text, which means that a treaty interpreter need not compare the authentic texts as a routine matter as a matter of law. Nevertheless, routine comparison of authentic texts would be good practice in the WTO context, since there are several discrepancies that could affect the interpretation of WTO provisions.

Multimodal viral communication: a social semiotic analysis of the popular Spanish "Ola ke ase" meme

Multimodality – the interdependence of semiotic resources in text – is an existential element of today’s media. The term multimodality attends systematically to the social interpretation of a wide range of communicational forms used in meaning making. A primary focus of social- semiotic multimodal analysis is on mapping how modal resources are used by people in a given social context. In November 2012 the “Ola ke ase” catchphrase, which is a play on “Hola ¿qué hace?”, appeared for the first time in Spain and immediately has been adopted as a Twitter hashtag and an image macro series. Its viral spread on social networks has been tremendous, being a trending topic in various Spanish-speaking countries. The objective of analysis is how language and image work together in the “Ola ke ase” meme. The interplay between text and image in one of the original memes and some of its variations is quantitatively analysed applying a social-semiotic approach. Results demonstrate how the “Ola ke ase” meme functions through its multimodal character and the non-standard orthography. The spread of uncountable variations of the meme shows the social process that goes on in the meaning making of the semiotic elements.

Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations

Background: Cerebral dysfunction occurring in mental disorders can show metabolic disturbances which are limited to circumscribed brain areas. Auditory hallucinations have been shown to be related to defined cortical areas linked to specific language functions. Here, we investigated if the study of metabolic changes in auditory hallucinations requires a functional rather than an anatomical definition of their location and size to allow a reliable investigation by magnetic resonance spectroscopy (MRS). Methods: Schizophrenia patients with (AH; n = 12) and without hallucinations (NH; n = 8) and healthy controls (HC; n = 11) underwent a verbal fluency task in functional MRI (fMRI) to functionally define Broca's and Wernicke's areas. Left and right Heschl's gyri were defined anatomically. Results: The mean distances in native space between the fMRI-defined regions and a corresponding anatomically defined area were 12.4 ± 6.1 mm (range: 2.7–36.1 mm) for Broca's area and 16.8 ± 6.2 mm (range: 4.5–26.4 mm) for Wernicke's area, respectively. Hence, the spatial variance was of similar extent as the size of the investigated regions. Splitting the investigations into a single voxel examination in the frontal brain and a spectroscopic imaging part for the more homogeneous field areas led to good spectral quality for almost all spectra. In Broca's area, there was a significant group effect (p = 0.03) with lower levels of N-acetyl-aspartate (NAA) in NH compared to HC (p = 0.02). There were positive associations of NAA levels in the left Heschl's gyrus with total (p = 0.03) and negative (p = 0.006) PANSS scores. In Broca's area, there was a negative association of myo-inositol levels with total PANSS scores (p = 0.008). Conclusion: This study supports the neurodegenerative hypothesis of schizophrenia only in a frontal region whereas the results obtained from temporal regions are in contrast to the majority of previous studies. Future research should test the hypothesis raised by this study that a functional definition of language regions is needed if neurochemical imbalances are expected to be restricted to functional foci.

Temporal lobe white matter asymmetry and language laterality in epilepsy patients.

Recent studies using diffusion tensor imaging (DTI) have advanced our knowledge of the organization of white matter subserving language function. It remains unclear, however, how DTI may be used to predict accurately a key feature of language organization: its asymmetric representation in one cerebral hemisphere. In this study of epilepsy patients with unambiguous lateralization on Wada testing (19 left and 4 right lateralized subjects; no bilateral subjects), the predictive value of DTI for classifying the dominant hemisphere for language was assessed relative to the existing standard-the intra-carotid Amytal (Wada) procedure. Our specific hypothesis is that language laterality in both unilateral left- and right-hemisphere language dominant subjects may be predicted by hemispheric asymmetry in the relative density of three white matter pathways terminating in the temporal lobe implicated in different aspects of language function: the arcuate (AF), uncinate (UF), and inferior longitudinal fasciculi (ILF). Laterality indices computed from asymmetry of high anisotropy AF pathways, but not the other pathways, classified the majority (19 of 23) of patients using the Wada results as the standard. A logistic regression model incorporating information from DTI of the AF, fMRI activity in Broca's area, and handedness was able to classify 22 of 23 (95.6%) patients correctly according to their Wada score. We conclude that evaluation of highly anisotropic components of the AF alone has significant predictive power for determining language laterality, and that this markedly asymmetric distribution in the dominant hemisphere may reflect enhanced connectivity between frontal and temporal sites to support fluent language processes. Given the small sample reported in this preliminary study, future research should assess this method on a larger group of patients, including subjects with bi-hemispheric dominance.

Jazz drummers recruit language-specific areas for the processing of rhythmic structure

Rhythm is a central characteristic of music and speech, the most important domains of human communication using acoustic signals. Here, we investigated how rhythmical patterns in music are processed in the human brain, and, in addition, evaluated the impact of musical training on rhythm processing. Using fMRI, we found that deviations from a rule-based regular rhythmic structure activated the left planum temporale together with Broca's area and its right-hemispheric homolog across subjects, that is, a network also crucially involved in the processing of harmonic structure in music and the syntactic analysis of language. Comparing the BOLD responses to rhythmic variations between professional jazz drummers and musical laypersons, we found that only highly trained rhythmic experts show additional activity in left-hemispheric supramarginal gyrus, a higher-order region involved in processing of linguistic syntax. This suggests an additional functional recruitment of brain areas usually dedicated to complex linguistic syntax processing for the analysis of rhythmical patterns only in professional jazz drummers, who are especially trained to use rhythmical cues for communication.