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.

Aviation English: Structure and Importance of an International Airborne Language

In today’s globalized world, air travel is one of the fastest growing markets. Millions of aircrafts take off and then touch down all around the world each day. This well-synchronized symphony, however, is much more complex than it seems, and communication – language - plays a crucial role during a plane’s journey. Misunderstandings and miscommunications can have disastrous effects, so the adoption of a standard phraseology to be used during flight is a means to overcome language barriers, avoid ambiguous expressions and guarantee a safe and effective operation of an aircraft. Little is known about the interaction that goes on between pilots and air traffic controllers (ATCOs), and even though the language of aviation is English, cockpit communication can be hard to understand for people who are not familiar with this specific language. The scope of this thesis is to examine the origins of this uncommon language, the characteristics and peculiarities of air communication and to shed a little light on this mystery called Aviation English.

General language abilities following management of childhood supratentorial tumour: Part 1

Background. To date few studies have investigated the impact of management for supratentorial tumour on the language abilities of children. In reporting children with brain tumour as part of a larger cohort of various aetiologies of brain injury, such studies have failed to differentiate between the causes of acquired childhood language disorders, or specifically report associated information relating to site and treatment. Material and methods. The present study examined the general language abilities of six children managed for supratentorial tumour, using a comprehensive standardized general language assessment battery, including receptive and expressive components, receptive vocabulary, and naming. Results. At a group level, children managed for supratentorial tumour performed below an individually matched control group in the area of general expressive language. However, at an individual case level it was revealed that only two cases exhibited specific language deficits. Reduced performance in the area of expressive language and syntax was evident in the language profile of one child treated surgically for a left parietal astrocytoma, while a child treated surgically for an optic nerve glioma demonstrated difficulties in receptive semantic abilities. The remaining four cases with similar treatments and locations demonstrated intact general language abilities. Conclusions. Factors such as site, long-term presence of tumour prior to diagnosis, young age at diagnosis, and variations in time post treatment were considered to have contributed to the findings. The need for long-term monitoring of language abilities post treatment as well as larger group sizes and the investigation of higher-level abilities was highlighted

Introduction of novel video-based tasks to clinical fMRI: Comparing traditional fMRI tasks with novel video-based tasks for mapping brain language areas

Recently, blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has become a routine clinical procedure for localization of language and motor brain regions and has been replacing more invasive preoperative procedures. However, the fMRI results from these tasks are not always reproducible even from the same patient. Evaluating the reproducibility of language and speech mapping is especially complicated due to the complex brain circuitry that may become activated during the functional task. Non-language areas such as sensory, attention, decision-making, and motor brain regions may also be activated in addition to the specific language regions during a traditional sentence-completion task. In this study, I test a new approach, which utilizes 4-minute video-based tasks, to map language and speech brain regions for patients undergoing brain surgery. Results from 35 subjects have shown that the video-based task activates Wernicke’s area, as well as Broca’s area in most subjects. The computed laterality indices, which indicate the dominant hemisphere from that functional task, have indicated left dominance from the video-based tasks. This study has shown that the video-based task may be an alternative method for localization of language and speech brain regions for patients who are unable to complete the sentence-completion task.

Improving cross language information retrieval using corpus based query suggestion approach

Users seeking information may not find relevant information pertaining to their information need in a specific language. But information may be available in a language different from their own, but users may not know that language. Thus users may experience difficulty in accessing the information present in different languages. Since the retrieval process depends on the translation of the user query, there are many issues in getting the right translation of the user query. For a pair of languages chosen by a user, resources, like incomplete dictionary, inaccurate machine translation system may exist. These resources may be insufficient to map the query terms in one language to its equivalent terms in another language. Also for a given query, there might exist multiple correct translations. The underlying corpus evidence may suggest a clue to select a probable set of translations that could eventually perform a better information retrieval. In this paper, we present a cross language information retrieval approach to effectively retrieve information present in a language other than the language of the user query using the corpus driven query suggestion approach. The idea is to utilize the corpus based evidence of one language to improve the retrieval and re-ranking of news documents in the other language. We use FIRE corpora - Tamil and English news collections in our experiments and illustrate the effectiveness of the proposed cross language information retrieval approach.

An Exploration of Auditory Brainstem Encoding of Stop Consonants in Infants and Implications for Language Outcomes

Current trends in speech-language pathology focus on early intervention as the preferred tool for promoting the best possible outcomes in children with language disorders. Neuroimaging techniques are being studied as promising tools for flagging at-risk infants. In this study, the auditory brainstem response (ABR) to the syllables /ba/ and /ga/ was examined in 41 infants between 3 and 12 months of age as a possible tool to predict language development in toddlerhood. The MacArthur-Bates Communicative Development Inventory (MCDI) was used to assess language development at 18 months of age. The current study compared the periodicity of the responses to the stop consonants and phase differences between /ba/ and /ga/ in both at-risk and low-risk groups. The study also examined whether there are correlations among ABR measures (periodicity and phase differentiation) and language development. The study found that these measures predict language development at 18 months.

Language-based Techniques for Practical and Trustworthy Secure Multi-party Computations

Secure Multi-party Computation (MPC) enables a set of parties to collaboratively compute, using cryptographic protocols, a function over their private data in a way that the participants do not see each other's data, they only see the final output. Typical MPC examples include statistical computations over joint private data, private set intersection, and auctions. While these applications are examples of monolithic MPC, richer MPC applications move between "normal" (i.e., per-party local) and "secure" (i.e., joint, multi-party secure) modes repeatedly, resulting overall in mixed-mode computations. For example, we might use MPC to implement the role of the dealer in a game of mental poker -- the game will be divided into rounds of local decision-making (e.g. bidding) and joint interaction (e.g. dealing). Mixed-mode computations are also used to improve performance over monolithic secure computations. Starting with the Fairplay project, several MPC frameworks have been proposed in the last decade to help programmers write MPC applications in a high-level language, while the toolchain manages the low-level details. However, these frameworks are either not expressive enough to allow writing mixed-mode applications or lack formal specification, and reasoning capabilities, thereby diminishing the parties' trust in such tools, and the programs written using them. Furthermore, none of the frameworks provides a verified toolchain to run the MPC programs, leaving the potential of security holes that can compromise the privacy of parties' data. This dissertation presents language-based techniques to make MPC more practical and trustworthy. First, it presents the design and implementation of a new MPC Domain Specific Language, called Wysteria, for writing rich mixed-mode MPC applications. Wysteria provides several benefits over previous languages, including a conceptual single thread of control, generic support for more than two parties, high-level abstractions for secret shares, and a fully formalized type system and operational semantics. Using Wysteria, we have implemented several MPC applications, including, for the first time, a card dealing application. The dissertation next presents Wys*, an embedding of Wysteria in F*, a full-featured verification oriented programming language. Wys* improves on Wysteria along three lines: (a) It enables programmers to formally verify the correctness and security properties of their programs. As far as we know, Wys* is the first language to provide verification capabilities for MPC programs. (b) It provides a partially verified toolchain to run MPC programs, and finally (c) It enables the MPC programs to use, with no extra effort, standard language constructs from the host language F*, thereby making it more usable and scalable. Finally, the dissertation develops static analyses that help optimize monolithic MPC programs into mixed-mode MPC programs, while providing similar privacy guarantees as the monolithic versions.

Advanced neuroimaging methodologies to improve connectivity detection in normal and abnormal language brain networks

The language connectome was in-vivo investigated using multimodal non-invasive quantitative MRI. In PPA patients (n=18) recruited by the IRCCS ISNB, Bologna, cortical thickness measures showed a predominant reduction on the left hemisphere (p<0.005) with respect to matched healthy controls (HC) (n=18), and an accuracy of 86.1% in discrimination from Alzheimer’s disease patients (n=18). The left temporal and para-hippocampal gyri significantly correlated (p<0.01) with language fluency. In PPA patients (n=31) recruited by the Northwestern University Chicago, DTI measures were longitudinally evaluated (2-years follow-up) under the supervision of Prof. M. Catani, King’s College London. Significant differences with matched HC (n=27) were found, tract-localized at baseline and widespread in the follow-up. Language assessment scores correlated with arcuate (AF) and uncinate (UF) fasciculi DTI measures. In left-ischemic stroke patients (n=16) recruited by the NatBrainLab, King’s College London, language recovery was longitudinally evaluated (6-months follow-up). Using arterial spin labelling imaging a significant correlation (p<0.01) between language recovery and cerebral blood flow asymmetry, was found in the middle cerebral artery perfusion, towards the right. In HC (n=29) recruited by the DIBINEM Functional MR Unit, University of Bologna, an along-tract algorithm was developed suitable for different tractography methods, using the Laplacian operator. A higher left superior temporal gyrus and precentral operculum AF connectivity was found (Talozzi L et al., 2018), and lateralized UF projections towards the left dorsal orbital cortex. In HC (n=50) recruited in the Human Connectome Project, a new tractography-driven approach was developed for left association fibres, using a principal component analysis. The first component discriminated cortical areas typically connected by the AF, suggesting a good discrimination of cortical areas sharing a similar connectivity pattern. The evaluation of morphological, microstructural and metabolic measures could be used as in-vivo biomarkers to monitor language impairment related to neurodegeneration or as surrogate of cognitive rehabilitation/interventional treatment efficacy.

Lateralized deficit of response inhibition in early-onset schizophrenia

Background. The ability to inhibit inappropriate or unwanted actions is a key element of executive control. The existence OF executive function deficits in schizophrenia is consistent with frontal lobe theories of the disorder. Relatively few Studies have examined response inhibition in schizophrenia, and none in adolescent patients with early-onset schizophrenia (EOS). Methods. Twenty-one adolescents with (lie onset of clinically impairing psychosis before 19 years of age and 16 matched controls performed a stop-signal task to assess response inhibition. The patients with EOS were categorized Lis paranoid (n= 10) and Undifferentiated subtypes (n= 11). The undifferentiated group had higher levels of negative symptomatology. Stop-signal reaction time (SSRT) and go-signal reaction time (Go-RT) were analysed with respect to hand of response. Results. The Undifferentiated early-onset patients had significantly longer SSRTs, indicative of poor response inhibition, for the left hand compared to the paranoid early-onset patients and control participants. No differences existed for inhibitory control with the right hand. The three groups did not differ in Go-RT. Conclusions. Our results indicate a specific lateralized impairment of response inhibition in patients With Undifferentiated, but not paranoid, EOS. These findings are consistent with reports of immature frontostriatal networks in EOS and implicate areas such as the pre-motor cortex and Supplementary motor area (SMA) that are thought to play a role in both voluntary initiation and inhibition of movement.

Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency

The Myc oncogene regulates the expression of several components of the protein synthetic machinery, including ribosomal proteins, initiation factors of translation, RNA polymerase III and ribosomal DNA(1,2). Whether and how increasing the cellular protein synthesis capacity affects the multistep process leading to cancer remains to be addressed. Here we use ribosomal protein heterozygote mice as a genetic tool to restore increased protein synthesis in E mu-Myc/+ transgenic mice to normal levels, and show that the oncogenic potential of Myc in this context is suppressed. Our findings demonstrate that the ability of Myc to increase protein synthesis directly augments cell size and is sufficient to accelerate cell cycle progression independently of known cell cycle targets transcriptionally regulated by Myc. In addition, when protein synthesis is restored to normal levels, Myc- overexpressing precancerous cells are more efficiently eliminated by programmed cell death. Our findings reveal a new mechanism that links increases in general protein synthesis rates downstream of an oncogenic signal to a specific molecular impairment in the modality of translation initiation used to regulate the expression of selective messenger RNAs. We show that an aberrant increase in cap- dependent translation downstream of Myc hyperactivation specifically impairs the translational switch to internal ribosomal entry site ( IRES)- dependent translation that is required for accurate mitotic progression. Failure of this translational switch results in reduced mitotic- specific expression of the endogenous IRES- dependent form of Cdk11 ( also known as Cdc21 and PITSLRE)(3-5), which leads to cytokinesis defects and is associated with increased centrosome numbers and genome instability in E mu-Myc/+ mice. When accurate translational control is re- established in E mu-Myc/+ mice, genome instability is suppressed. Our findings demonstrate how perturbations in translational control provide a highly specific outcome for gene expression, genome stability and cancer initiation that have important implications for understanding the molecular mechanism of cancer formation at the post- genomic level.

Rasmussen encephalitis: long-term outcome after surgery

Rasmussen encephalitis (RE) is characterized by intractable epilepsy, progressive hemiparesis, and unilateral hemispheric atrophy. The progression of the symptoms to significant neurological impairment usually occurs within months to a few years. RE causes are unknown, although evidence of an autoimmune process has been extensively described in the literature. Antiepileptic drugs are usually not effective to control seizures or cerebral atrophy; despite data supporting a beneficial effect of early immunosuppressive and immunomodulatory interventions, for intractable seizures in RE patients with advanced disease, epilepsy surgery in the form of hemispheric disconnection has been considered the treatment of choice. This work describes the clinical and electrographic analyses, as well as the post-operative evolution of patients with RE. This work includes all the patients with RE evaluated from January 1995 to January 2008 by the RibeirA o pound Preto Epilepsy Surgery Program (CIREP), taking variables such as gender; age at epilepsy onset; seizure semiology; seizure frequency; interictal and ictal electroencephalographic (EEG) findings; age at surgery, when done; duration of epilepsy; surgery complications; follow-up duration; anatomo-pathological findings; post-surgery seizure; language and cognitive outcome; and anti-epileptic drug treatment after surgery into account. Twenty-five patients were evaluated; thirteen were female. Mean age of epilepsy onset was 4.4 +/- 2.0 years. There were no differences between patients with slow and fast evolution with respect to age of epilepsy onset (p = 0.79), age at surgery (p = 0.24), duration of epilepsy (0.06), and follow-up (p = 0.40). There were no correlations between the presence of bilateral EEG abnormalities or the absence of spikes and post-operative seizure outcome (p = 0.06). Immunomodulatory therapy was tried in 12 patients (48%). Twenty-three patients underwent surgery. The mean follow-up was 63.3 months. Eleven patients had total seizure control. Twelve individuals persisted with seizures consisting of mild facial jerks (six patients), occasional hemigeneralized tonic-clonic seizures (three patients), and frequent tonic-clonic seizures (three patients). Mental and language impairment was observed in 15 and 12 patients, after surgery, respectively. Eight patients presented post-operative cognitive decline, while only two patients had cognitive improvement. Comparing pre- and post-operative language deficits, 66.7% of the 12 patients with language disturbance did not improve after surgery. This retrospective study reported the clinical and electrographic analysis, as well as the evolution of 23 patients with RE. Patients were divided into two groups: fast evolution and slow evolution to hemiparesis and epilepsia partialis continua. These groups may represent different RE substrates. Fourteen patients achieved satisfactory seizure control, three patients had partial response to surgery, and five patients had maintenance of the pre-operative condition. All patients with left-side involvement presented with some language disturbance, which did not improve after surgery in 66.6% of patients. Cognitive evaluation showed that the majority of the patients did not have any significant improvement, and 38.1% had cognitive deterioration after surgery.

MDA-based re-engineering with Object-Z

This paper describes a practical application of MDA and reverse engineering based on a domain-specific modelling language. A well defined metamodel of a domain-specific language is useful for verification and validation of associated tools. We apply this approach to SIFA, a security analysis tool. SIFA has evolved as requirements have changed, and it has no metamodel. Hence, testing SIFA’s correctness is difficult. We introduce a formal metamodelling approach to develop a well-defined metamodel of the domain. Initially, we develop a domain model in EMF by reverse engineering the SIFA implementation. Then we transform EMF to Object-Z using model transformation. Finally, we complete the Object-Z model by specifying system behavior. The outcome is a well-defined metamodel that precisely describes the domain and the security properties that it analyses. It also provides a reliable basis for testing the current SIFA implementation and forward engineering its successor.

Identificação das categorias mais relevantes da classificação internacional de funcionalidade, incapacidade e saúde para os terapeutas ocupacionais que exercem funções em unidades de cuidados continuados integrados

As constantes alterações das realidades sociais e epidemiológicas em associação ao envelhecimento populacional conduziram a insuficiências dos Sistemas Social e de Saúde que requerem uma reestruturação ao nível da adequação dos cuidados de saúde a prestar, pelo que, em resposta a esta necessidade foi criada a Rede Nacional de Cuidados Continuados Integrados. O presente estudo, de natureza qualitativa e carácter exploratório, tem como objectivo compreender a percepção dos Terapeutas Ocupacionais que trabalham em Unidades de Cuidados Continuados Integrados relativamente às categorias que considerem mais relevantes da Classificação Internacional da Funcionalidade, Incapacidade e Saúde, tendo sido aplicada uma entrevista a 8 profissionais a exercer funções em Unidades da Zona Norte, resultante de um processo de amostragem não probabilística e de conveniência. Como método de recolha de dados foi aplicada uma entrevista semi-estruturada, cujo guião foi construído após revisão bibliográfica, tendo por base as categorias definidas pelo modelo da Classificação Internacional da Funcionalidade, Incapacidade e Saúde e, posteriormente, analisado por um painel de peritos, tendo-se procedido à realização de uma entrevista piloto a um elemento, sem que esta contasse para a análise. A partir da análise das entrevistas realizadas procedemos à identificação das unidades de significado, tendo os conceitos sido ligados às categorias da Classificação que o representam de uma forma mais adequada, de acordo com as linking rules, tendo sido identificadas as categorias mais relevantes para os Terapeutas Ocupacionais a exercer funções em Unidades de Cuidados Continuados Integrados. Com a realização deste estudo, que pretende ser um primeiro passo para a criação de um futuro Core Set em Cuidados Continuados, foi-nos possível verificar que o maior número de categorias foram observadas no componente Actividades e Participação, tendo sido contabilizadas 70 (40,7%). Por outro lado, o componente Estruturas do corpo é o que integra menor número, contando com 19 categorias (11,05%). Assim, pensamos que a criação de um Core Set em Cuidados Continuados poderá beneficiar e facilitar a comunicação entre os profissionais destas equipas. No entanto, é importante ressalvar que a terminologia desta Classificação deverá ser utilizada de uma forma concertada com a linguagem específica da Terapia Ocupacional. Palavras-chave: Classificação Internacional da Funcionalidade, Incapacidade e Saúde, Core Set, Terapeutas Ocupacionais, Unidades de Cuidados Continuados Integrados.

Automatização de testes à framework myMIS

Atualmente, verifica-se um aumento na necessidade de software feito à medida do cliente, que se consiga adaptar de forma rápida as constantes mudanças da sua área de negócio. Cada cliente tem os seus problemas concretos que precisa de resolver, não lhe sendo muitas vezes possível dispensar uma elevada quantidade de recursos para atingir os fins pretendidos. De forma a dar resposta a estes problemas surgiram várias arquiteturas e metodologias de desenvolvimento de software, que permitem o desenvolvimento ágil de aplicações altamente configuráveis, que podem ser personalizadas por qualquer utilizador das mesmas. Este dinamismo, trazido para as aplicações sobre a forma de modelos que são personalizados pelos utilizadores e interpretados por uma plataforma genérica, cria maiores desafios no momento de realizar testes, visto existir um número de variáveis consideravelmente maior que numa aplicação com uma arquitetura tradicional. É necessário, em todos os momentos, garantir a integridade de todos os modelos, bem como da plataforma responsável pela sua interpretação, sem ser necessário o desenvolvimento constante de aplicações para suportar os testes sobre os diferentes modelos. Esta tese debruça-se sobre uma aplicação, a plataforma myMIS, que permite a interpretação de modelos orientados à gestão, escritos numa linguagem específica de domínio, sendo realizada a avaliação do estado atual e definida uma proposta de práticas de testes a aplicar no desenvolvimento da mesma. A proposta resultante desta tese permitiu verificar que, apesar das dificuldades inerentes à arquitetura da aplicação, o desenvolvimento de testes de uma forma genérica é possível, podendo as mesmas lógicas ser utilizadas para o teste de diversos modelos distintos.

Análise qualitativa do impacto do programa de treino metacognitivo

Neste estudo procuramos determinar a satisfação e a percepção de mudanças específicas resultantes da participação num programa de treino metacognitivo e da cognição social (TMSC) para pessoas com Esquizofrenia. Participaram 21 participantes com diagnóstico de Esquizofrenia responderam a um inquérito por questionário de administração direta com questões abertas, realizado a meio e no final do TMCS. A partir das categorias (1) Satisfação com o programa, (2) Reestruturação sócio-cognitiva e (3) Mudanças na relação eu-outro, verificamos que o programa é relevante, tem potencial para introduzir mudanças na relação com os outros e parece otimizar a cognição social. Os aspectos negativos apontados estão relacionados com a duração do programa e das sessões, e com a linguagem utilizada.