Investigation of multisensory processing and structural brain differences in Autism Spectrum Disorder

This thesis is an investigation of structural brain abnormalities, as well as multisensory and unisensory processing deficits in autistic traits and Autism Spectrum Disorder (ASD). To achieve this, structural and functional magnetic resonance imaging (fMRI) and psychophysical techniques were employed. ASD is a neurodevelopmental condition which is characterised by the social communication and interaction deficits, as well as repetitive patterns of behaviour, interests and activities. These traits are thought to be present in a typical population. The Autism Spectrum Quotient questionnaire (AQ) was developed to assess the prevalence of autistic traits in the general population. Von dem Hagen et al. (2011) revealed a link between AQ with white matter (WM) and grey matter (GM) volume (using voxel-based-morphometry). However, their findings revealed no difference in GM in areas associated with social cognition. Cortical thickness (CT) measurements are known to be a more direct measure of cortical morphology than GM volume. Therefore, Chapter 2 investigated the relationship between AQ scores and CT in the same sample of participants. This study showed that AQ scores correlated with CT in the left temporo-occipital junction, left posterior cingulate, right precentral gyrus and bilateral precentral sulcus, in a typical population. These areas were previously associated with structural and functional differences in ASD. Thus the findings suggest, to some extent, autistic traits are reflected in brain structure - in the general population. The ability to integrate auditory and visual information is crucial to everyday life, and results are mixed regarding how ASD influences audiovisual integration. To investigate this question, Chapter 3 examined the Temporal Integration Window (TIW), which indicates how precisely sight and sound need to be temporally aligned so that a unitary audiovisual event can be perceived. 26 adult males with ASD and 26 age and IQ-matched typically developed males were presented with flash-beep (BF), point-light drummer, and face-voice (FV) displays with varying degrees of asynchrony and asked to make Synchrony Judgements (SJ) and Temporal Order Judgements (TOJ). Analysis of the data included fitting Gaussian functions as well as using an Independent Channels Model (ICM) to fit the data (Garcia-Perez & Alcala-Quintana, 2012). Gaussian curve fitting for SJs showed that the ASD group had a wider TIW, but for TOJ no group effect was found. The ICM supported these results and model parameters indicated that the wider TIW for SJs in the ASD group was not due to sensory processing at the unisensory level, but rather due to decreased temporal resolution at a decisional level of combining sensory information. Furthermore, when performing TOJ, the ICM revealed a smaller Point of Subjective Simultaneity (PSS; closer to physical synchrony) in the ASD group than in the TD group. Finding that audiovisual temporal processing is different in ASD encouraged us to investigate the neural correlates of multisensory as well as unisensory processing using functional magnetic resonance imaging fMRI. Therefore, Chapter 4 investigated audiovisual, auditory and visual processing in ASD of simple BF displays and complex, social FV displays. During a block design experiment, we measured the BOLD signal when 13 adults with ASD and 13 typically developed (TD) age-sex- and IQ- matched adults were presented with audiovisual, audio and visual information of BF and FV displays. Our analyses revealed that processing of audiovisual as well as unisensory auditory and visual stimulus conditions in both the BF and FV displays was associated with reduced activation in ASD. Audiovisual, auditory and visual conditions of FV stimuli revealed reduced activation in ASD in regions of the frontal cortex, while BF stimuli revealed reduced activation the lingual gyri. The inferior parietal gyrus revealed an interaction between stimulus sensory condition of BF stimuli and group. Conjunction analyses revealed smaller regions of the superior temporal cortex (STC) in ASD to be audiovisual sensitive. Against our predictions, the STC did not reveal any activation differences, per se, between the two groups. However, a superior frontal area was shown to be sensitive to audiovisual face-voice stimuli in the TD group, but not in the ASD group. Overall this study indicated differences in brain activity for audiovisual, auditory and visual processing of social and non-social stimuli in individuals with ASD compared to TD individuals. These results contrast previous behavioural findings, suggesting different audiovisual integration, yet intact auditory and visual processing in ASD. Our behavioural findings revealed audiovisual temporal processing deficits in ASD during SJ tasks, therefore we investigated the neural correlates of SJ in ASD and TD controls. Similar to Chapter 4, we used fMRI in Chapter 5 to investigate audiovisual temporal processing in ASD in the same participants as recruited in Chapter 4. BOLD signals were measured while the ASD and TD participants were asked to make SJ on audiovisual displays of different levels of asynchrony: the participants’ PSS, audio leading visual information (audio first), visual leading audio information (visual first). Whereas no effect of group was found with BF displays, increased putamen activation was observed in ASD participants compared to TD participants when making SJs on FV displays. Investigating SJ on audiovisual displays in the bilateral superior temporal gyrus (STG), an area involved in audiovisual integration (see Chapter 4), we found no group differences or interaction between group and levels of audiovisual asynchrony. The investigation of different levels of asynchrony revealed a complex pattern of results indicating a network of areas more involved in processing PSS than audio first and visual first, as well as areas responding differently to audio first compared to video first. These activation differences between audio first and video first in different brain areas are constant with the view that audio leading and visual leading stimuli are processed differently.

Vandetanib for the Treatment of Advanced Medullary Thyroid Cancer Outside a Clinical Trial: Results from a French Cohort

International audience

Geological Evolution of Coastal and Marine Environments off the Campania Continental Shelf Through Marine Geological Mapping - The Example of the Cilento Promontory

The geological evolution of coastal and marine environments offshore the Cilento Promontory through marine geological mapping is discussed here. The marine geological map n. 502 “Agropoli,” located offshore the Cilento Promontory (southern Italy), is described and put in regional geologic setting. The study area covers water depths ranging between 30 and 200 m isobaths. The geologic map has been constructed in the frame of a research program financed by the National Geological Survey of Italy (CARG Project), finalized to the construction of an up-to-date cartography of the Campania region. Geological and geophysical data on the continental shelf and slope offshore the southern Campania region have been acquired in an area bounded northward by the Gulf of Salerno and southward by the Gulf of Policastro. A high-resolution multibeam bathymetry has permitted the construction of a digital elevation model (DEM). Sidescan sonar profiles have also been collected and interpreted, and their merging with bathymetric data has allowed for the realization of the base for the marine geologic cartography. The calibration of geophysical data has been attempted through sea-bottom samples. The morpho-structures and the seismic sequences overlying the outcrops of acoustic basement reported in the cartographic representation have been studied in detail using single-channel seismics. The interpretation of seismic profiles has been a support for the reconstruction of the stratigraphic and structural setting of the Quaternary continental shelf successions and the outcrops of rocky acoustic basement in correspondence to the Licosa Cape morphostructural high. These areas result from the seaward prolongation of the stratigraphic and structural units, widely cropping out in the surrounding emerged sector of the Cilento Promontory. The cartographic approach is based on the recognition of laterally coeval depositional systems, interpreted in the frame of system tracts of the Late Quaternary depositional sequence.

Recommended reporting standards for test accuracy studies of infectious diseases of finfish, amphibians, molluscs and crustaceans: the STRADAS-aquatic checklist

Complete and transparent reporting of key elements of diagnostic accuracy studies for infectious diseases in cultured and wild aquatic animals benefits end-users of these tests, enabling the rational design of surveillance programs, the assessment of test results from clinical cases and comparisons of diagnostic test performance. Based on deficiencies in the Standards for Reporting of Diagnostic Accuracy (STARD) guidelines identified in a prior finfish study (Gardner et al. 2014), we adapted the Standards for Reporting of Animal Diagnostic Accuracy Studies—paratuberculosis (STRADAS-paraTB) checklist of 25 reporting items to increase their relevance to finfish, amphibians, molluscs, and crustaceans and provided examples and explanations for each item. The checklist, known as STRADAS-aquatic, was developed and refined by an expert group of 14 transdisciplinary scientists with experience in test evaluation studies using field and experimental samples, in operation of reference laboratories for aquatic animal pathogens, and in development of international aquatic animal health policy. The main changes to the STRADAS-paraTB checklist were to nomenclature related to the species, the addition of guidelines for experimental challenge studies, and the designation of some items as relevant only to experimental studies and ante-mortem tests. We believe that adoption of these guidelines will improve reporting of primary studies of test accuracy for aquatic animal diseases and facilitate assessment of their fitness-for-purpose. Given the importance of diagnostic tests to underpin the Sanitary and Phytosanitary agreement of the World Trade Organization, the principles outlined in this paper should be applied to other World Organisation for Animal Health (OIE)-relevant species.

Crocin and β-Carotene bleaching assays as analytical tools in the optimization of the extraction of hydrophilic and lipophilic antioxidants from tomato

Tomato (Lycopersicon esculentum Mill.) is the second most important vegetable crop worldwide and a rich source of hydrophilic (H) and lipophilic (L) antioxidants. The H fraction is constituted mainly by ascorbic acid and soluble phenolic compounds, while the L fraction contains carotenoids (mostly lycopene), tocopherols, sterols and lipophilic phenolics [1,2]. To obtain these antioxidants it is necessary to follow appropriate extraction methods and processing conditions. In this regard, this study aimed at determining the optimal extraction conditions for H and L antioxidants from a tomato surplus. A 5-level full factorial design with 4 factors (extraction time (I, 0-20 min), temperature (T, 60-180 •c), ethanol percentage (Et, 0-100%) and solid/liquid ratio (S/L, 5-45 g!L)) was implemented and the response surface methodology used for analysis. Extractions were carried out in a Biotage Initiator Microwave apparatus. The concentration-time response methods of crocin and P-carotene bleaching were applied (using 96-well microplates), since they are suitable in vitro assays to evaluate the antioxidant activity of H and L matrices, respectively [3]. Measurements were carried out at intervals of 3, 5 and 10 min (initiation, propagation and asymptotic phases), during a time frame of 200 min. The parameters Pm (maximum protected substrate) and V m (amount of protected substrate per g of extract) and the so called IC50 were used to quantify the response. The optimum extraction conditions were as follows: r~2.25 min, 7'=149.2 •c, Et=99.1 %and SIL=l5.0 giL for H antioxidants; and t=l5.4 min, 7'=60.0 •c, Et=33.0% and S/L~l5.0 g/L for L antioxidants. The proposed model was validated based on the high values of the adjusted coefficient of determination (R2.wi>0.91) and on the non-siguificant differences between predicted and experimental values. It was also found that the antioxidant capacity of the H fraction was much higher than the L one.

Report of the Working Group on Introductions and Transfers of Marine Organisms (WGITMO). 16-18 March 2016 Olbia, Italy

The 42th meeting of the ICES Working Group on Introductions and Transfers of Marine Organisms (WGITMO) was held in Olbia, Italy, 16–18 March 2016, with Anna Occhipinti-Ambrogi as host and Henn Ojaveer as chairperson. Representatives from 19 countries participated in the meeting. Attendants were from Belgium, Canada, Dennark, Estonia, Finland, France, Germany, Ireland, Israel, Italy, Lithuania, Norway, Poland, Portugal, Russia, Spain, Sweden, United Kingdom and United States. Sweden contributed by cor-respondence. The objectives of the meeting were to update information and discuss several aspects related to the introductions and transfers of non-indigenous aquatic species. Data and information management were two of the discussion topics of the meeting, with special focus on the better exploitation of the ‘Information system on aquatic non-indigenous and cryptogenic species’ (AquaNIS). The WGITMO also dedicated time for addressing the MSFD D2 issues: indicator on new non-indigenous species introduced by human activities, and opportunities and problems related to cross-regional comparison of non-indigenous species indicators. Preparation of the manuscript of the alert report on sea squirt Didemnum vexillum, which is to be published in ICES CRR series, was discussed and the steps to be taken to finalise the report were agreed. As usual, adequate time was devoted to discuss national reports, to exchange of information on the management of NIS and to review ongoing and planned research activities. The approach taken during the meeting facilitated presentations and discussions on the issues of relevance related to the Terms of References as well as on a few generic and strategically-important issues of general relevance to bioinvasions. The meeting began with a full-day joint meeting with the Working Group on Ballast and Other Ship Vectors (WGBOSV), which provided an opportunity to discuss and address issues of common interest, such as shipping and biofouling as introduction vectors. The proposed ICES demonstration advice on ‘Risk management of non-indigenous species associated with shipping in the Arctic’ was discussed, and edits were suggested for both the orientation of the demonstration advice as well as for the exact questions to be asked. Both working groups agreed that the practice of conducting back-to-back meetings with one joint day is useful and will continue in 2017. All Terms of References to be addressed for 2016 were discussed. For some Terms of Ref-erence, more detailed presentations were given, and a short overview of the information and subsequent discussion is provided herein at the end of each section. This report is structured so that each Term of Reference is dealt with in sequential order. The main body of the report contains summaries of the presentations and discussions with the more detailed documents being contained in the Annexes. WGITMO progressed each of the Terms of Reference by either completing the task or clearly identifying and agreeing on the inter-sessional activities required to still finalise the work in 2016. From 2017, WGITMO will be shifted to multi-annual management.

Phenolic compounds and antioxidant capacity of three thymus species plants

Thymus plants comprise distinct species with claimed health properties [1], commonly associated to their essential oils and phenolic compounds. Albeit that, the phenolic composition and the biological activities of many Thymus species remain unclear. This work aimed to elucidate the phenolic composition and antioxidant properties of aqueous extracts from Thymus herba barona, Thymus caespetitus and Thymus fragrantissimus. The aqueous extracts of the three Thymus species were evaluated for their total phenolic compounds by an adaptation of the Folin-Ciocalteu method [2], and individual phenolic compounds were identified by high performance liquid chromatography associated with electrospray mass spectrometry (HPLC-DAD-ESI-MSn) in the negative mode. The antioxidant activity of each extract was carried out by DPPH● scavenging assay and ferric reducing antioxidant power assays [3]. Total phenolic compounds in the three extracts ranged from 236±27 (T. caespetitus) to 273±17 μg GAE/mg (T. fragrantissimus). Similarly to other Thymus species [1,4], these extracts were rich in caffeic acid derivatives (characteristic UV spectra maxima at 290 and 328 nm) and mainly composed of rosmarinic acid (MW 360). Other caffeic acid derivatives included salvianolic acid K (MW 556) and 3′-O-(8″-Z-caffeoyl)rosmarinic acid (MW 538). High amounts of the flavone luteolin-O-glucuronide ([M-H]− at m/z 461→285) were found in T. caespetitus while the others species contained moderate amounts of this compound. T. herba barona, T. caespetitus and T. fragrantissimus extracts showed high DPPH radical scavenge ability (EC50 values 11.6±0.9, 13.8±0.6 and 10.9±1.2 μg/mL respectively), as well as high reducing power (EC50 values of 35.1±4.5, 39.3±2.7 and 32.4±4.3 μg/mL, respectively), that were comparable to those of reference compounds. This work is an important contribution for the phytochemical characterization and the antioxidant capacity of these three Thymus species.

Phenolic compounds and antioxidant capacity of three thymus species plants

Thymus plants comprise distinct species with claimed health properties [1], commonly associated to their essential oils and phenolic compounds. Albeit that, the phenolic composition and the biological activities of many Thymus species remain unclear. This work aimed to elucidate the phenolic composition and antioxidant properties of aqueous extracts from Thymus herba barona, Thymus caespetitus and Thymus fragrantissimus. The aqueous extracts of the three Thymus species were evaluated for their total phenolic compounds by an adaptation of the Folin-Ciocalteu method [2], and individual phenolic compounds were identified by high performance liquid chromatography associated with electrospray mass spectrometry (HPLC-DAD-ESI-MSn) in the negative mode. The antioxidant activity of each extract was carried out by DPPH● scavenging assay and ferric reducing antioxidant power assays [3]. Total phenolic compounds in the three extracts ranged from 236±27 (T. caespetitus) to 273±17 μg GAE/mg (T. fragrantissimus). Similarly to other Thymus species [1,4], these extracts were rich in caffeic acid derivatives (characteristic UV spectra maxima at 290 and 328 nm) and mainly composed of rosmarinic acid (MW 360). Other caffeic acid derivatives included salvianolic acid K (MW 556) and 3′-O-(8″-Z-caffeoyl)rosmarinic acid (MW 538). High amounts of the flavone luteolin-O-glucuronide ([M-H]− at m/z 461→285) were found in T. caespetitus while the others species contained moderate amounts of this compound. T. herba barona, T. caespetitus and T. fragrantissimus extracts showed high DPPH radical scavenge ability (EC50 values 11.6±0.9, 13.8±0.6 and 10.9±1.2 μg/mL respectively), as well as high reducing power (EC50 values of 35.1±4.5, 39.3±2.7 and 32.4±4.3 μg/mL, respectively), that were comparable to those of reference compounds. This work is an important contribution for the phytochemical characterization and the antioxidant capacity of these three Thymus species.

Assessment of positive parenting programmes in the Autonomous Region of the Basque Country (Spain)

This paper presents the results of a study aimed at identifying and assessing positive parenting programmes and activities carried out in the Autonomous Region of the Basque Country (ARBC), Spain. The study is a development of the III Inter-institutional Family Support Plan (2011), drafted by the Basque Government's Department of Family Policy and Community Development, and its aim is to offer a series of sound criteria for improving existing programmes and ensuring the correct design and implementation of new ones in the future. It analyses 129 programmes and gathers data relative to institutional management and coordination, format, quality of the established aims, adaptation to the theoretical proposal for an Optimal Positive Parenting Curriculum, scientific base, use of the framework of reference for competences, working method, assessment techniques, budgets and publicity, among others. The results highlight the good quality of the programmes' aims and content, and the poor systematic assessment of these same aspects. The study concludes with a series of recommendations for improving the initiatives, integrated into a proposal for a system of indicators to assess and implement positive parenting programmes.

Report of the Stock Identification Methods Working Group (SIMWG) 2016

The Stock Identification Methods Working Group (SIMWG) worked by correspondence in 2016. The working group was chaired by Lisa Kerr (USA). The work plan for SIMWG in 2016 comprised four Terms of Reference (ToR), some of which are continuing goals for SIMWG: a ) Review recent advances in stock identification methods; b ) Build a reference database with updated information on known biological stocks for species of ICES interest; c ) Provide technical reviews and expert opinions on matters of stock identifica-tion, as requested by specific Working Groups and SCICOM; d ) Review and report on advances in mixed stock analysis, and assess their po-tential role in improving precision of stock assessment. ToR a) is an ongoing task of SIMWG in which we provide a comprehensive update on recent applications of stock identification techniques to ICES species of interest, summa-rize new approaches in stock identification, and novel combinations of existing applica-tions. ToR b) is a multi-annual ToR in which SIMWG has taking steps to build a reference data-base consisting of SIMWG reviews of issues of stock identity for ICES species. ToR c) is a key ongoing task by SIMWG in which we addresses specific requests by ICES working groups for technical advice on issues of stock identity. This year we provided advice on mackerel in the Northeast Atlantic as requested by WGWIDE. ToR d) is a multi-annual ToR that is focused on tracking developments in the application of mixed stock analysis and the integration of this information into assessment and management.

Report of the Working Group for the Bay of Biscay and the Iberian waters Ecoregion (WGBIE). 13-19 May 2016, ICES HQ, Copenhagen, Denmark

The ICES Working Group for the Bay of Biscay and the Iberic waters Ecoregion (WGBIE) met in Copenhagen, Denmark during 13–14 May 2016. There were 22 stocks in its remit distributed from ICES Divisions 3.a–4.a though mostly distributed in Sub Areas 7, 8 and 9. There were 21 participants, some of whom joined the meeting re-motely. The group was tasked with conducting assessments of stock status for 22 stocks using analytical, forecast methods or trends indicators to provide catch forecasts for eight stocks and provide a first draft of the ICES advice for 2016 for fourteen stocks. For the remaining stocks, the group had to update catch information and indices of abundance where needed. Depending on the result of this update, namely if it would change the perception of the stock, the working group drafted new advice. Analytical assessments using age-structured models were conducted for the northern and southern stocks of megrim and the Bay of Biscay sole. The two hake stocks and one southern stock of anglerfish were assessed using models that allow the use of only length-structured data (no age data). A surplus-production model, without age or length structure, was used to assess the second southern stocks of anglerfish. No ana-lytical assessments have been provided for the northern stocks of anglerfish after 2006. This is mostly due to ageing problems and to an increase in discards in recent years, for which there is no reliable data at the stock level. The state of stocks for which no analytical assessment could be performed was inferred from examination of commer-cial LPUE or CPUE data and from survey information. Three nephrops stocks from the Bay of Biscay and the Iberian waters are scheduled for benchmark assessments in October 2016. The WGBIE meeting spent some time review-ing the progress towards the benchmark (see Annex 6) together with longer term benchmarks (2017 and after, see section 1.) for sea bass in the Bay of Biscay, all an-glerfish and hake stocks assessed by the WG. For the northern megrim stock, the sched-ule an inter-benchmark meeting was completed successfully and the group reviewed the outcome and accepted the category 1 update assessment. A recurrent issue significantly constrained the group’s ability to address the terms of reference this year. Despite an ICES data call with a deadline of six weeks before the meeting, data for several stocks were resubmitted during the meeting which lead to increased workloads during the working group, as in that case, the assessments could not be carried out in National Laboratories prior to the meeting as mentioned in the ToRs. This is an important matter of concerns for the group members. Section 1 of the report presents a summary by stock and discusses general issues. Sec-tion 2 provides descriptions of the relevant fishing fleets and surveys used in the as-sessment of the stocks. Sections 3–18 contains the single stock assessments.

Development of new analytical procedures of isotope geochemistry by mass spectrometry. Application to the study of high-pressure metamorphic rocks from the Iberian Massif

319 p.

Europeanization beyond the EU: The case of Georgia.

320 p.

Development of combined acidification and separation of slurry: effect on slurry fractions composition and gaseous emission

Doutoramento em Engenharia do Ambiente - Instituto Superior de Agronomia - UL

A doutrina nacional de emprego de forças paraquedistas

Este Trabalho de Investigação Aplicada está enquadrado nas Tropas Paraquedistas portuguesas e é subordinado ao tema “A doutrina nacional de emprego de forças paraquedistas”. e tem como objetivo contribuir para a identificação de possíveis lacunas na doutrina das Tropas Paraquedistas portuguesas. Consistiu na análise da doutrina, nacional e de referência, existente para as Tropas Paraquedistas, bem como a consulta de entidades responsáveis pelas Unidades Paraquedistas, por forma a averiguar a adequabilidade, bem como as lacunas da atual doutrina que rege o emprego, treino e formação das Tropas Paraquedistas portuguesas. Utilizando o método hipotético-dedutivo, juntamente com uma análise bibliográfica da doutrina existente tanto a nível nacional como internacional, bem como entrevistas feitas a entidades que estão, ou estiveram, diretamente ligadas com o comando de Tropas Paraquedistas, foi recolhida a informação necessária para a elaboração desta investigação. Como resultado, concluiu-se que a doutrina nacional de emprego de Tropas Paraquedistas se encontra atualizada, dando respostas às solicitações que lhes são exigidas, sendo necessário, no entanto, um constante acompanhamento doutrinário.