Primary progressive aphasia

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A MEG study of the neural substrates of semantic processing in semantic variant primary progressive aphasia

A MEG study of the neural substrates of semantic processing in semantic variant primary progressive aphasia

Introduction Semantic variant primary progressive aphasia (svPPA), also described in the literature as semantic dementia, is a neurodegenerative disorder characterized by an insidious breakdown of conceptual knowledge (Hodges, Patterson, Oxbury, & Funnell, 1992; Snowden, Goulding, & Neary, 1989; Warrington, 1975). The conceptual loss observed in svPPA is sensitive to specific properties of words, such as frequency/familiarity, prototypicality, and the level of specificity (taxonomy) of semantic processing required for these concepts (Ralph, Jefferies, Patterson, & Rogers, 2017; Rogers et al., 2006). Regarding taxonomy, knowledge of properties that allow to individuate a specific concept from its semantic neighbors (e.g., a husky has blue eyes) is more vulnerable to decline than knowledge about properties shared by related concepts of the same category (e.g., a husky has four legs)(Catricalà et al., 2015). Therefore, patients are more impaired on tasks that require objects to be classified with greater precision (Patterson, Nestor, & Rogers, 2007; Ralph and Patterson, 2008). This taxonomic impairment has been documented in an array of tasks recruiting various input/output modalities (naming, word– picture matching, drawing, object recognition, coloring, lexical decision, and object use (Papagno and Capitani, 2001; Patterson et al., 2006; Rogers et al., 2004; Snowden, Neary, & Mann, 1996; Warrington, 1975). It is also observed during spontaneous speech in svPPA patients, who tend to gradually replace the specific terms previously used to describe objects by more general words (e.g. thing), thus affecting their conversational intelligibility.
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The role of the hippocampus in the semantic variant of primary progressive aphasia : a resting‐state fcMRI study

The role of the hippocampus in the semantic variant of primary progressive aphasia : a resting‐state fcMRI study

ABSTRACT The goal of the study was to determine whether the semantic variant of primary progressive aphasia (svPPA) affects the intrinsic connectivity network anchored to left and right anterior hippocampus, but spares the posterior hippocampus. A resting-state functional connectivity MRI (rs- fcMRI) study was conducted in a group of patients with svPPA and in controls, using a seed-to-voxel approach. In comparison to controls, massively reduced connectivity was found in the anterior

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Differential language network functional connectivity alterations in Alzheimer's disease and the semantic variant of primary progressive aphasia

Differential language network functional connectivity alterations in Alzheimer's disease and the semantic variant of primary progressive aphasia

Abstract Patients with Alzheimer’s disease (AD) and semantic variant primary progressive aphasia (svPPA) can present with similar language impairments, mainly in naming. It has been hypothesized that these deficits are associated with different brain mechanisms in each disease, but no previous study has used a network approach to explore this hypothesis. The aim of this study was to compare resting-state functional magnetic resonance imaging (rs-fMRI) language network in AD, svPPA patients, and cognitively unimpaired elderly adults (CTRL). Therefore, 10 AD patients, 12 svPPA patients and 11 CTRL underwent rs-fMRI. Seed-based functional connectivity analyses were conducted using regions of interest in the left anterior temporal lobe (ATL), left posterior middle temporal gyrus (pMTG) and left inferior frontal gyrus (IFG), applying a voxelwise correction for gray matter volume. In AD patients, the left pMTG was the only key language region showing functional connectivity changes, mainly a reduced interhemispheric functional connectivity with its right-hemisphere counterpart, in comparison to CTRL. In svPPA patients, we observed a functional isolation of the left ATL, both decreases and increases in functional connectivity from the left pMTG and increased functional connectivity form the left IFG. Post-hoc analyses showed that naming impairments were overall associated with the functional disconnections observed across the language network. In conclusion, AD and svPPA patients present distinct language network functional connectivity profiles. In AD patients, functional connectivity changes were restricted to the left pMTG and were overall less severe in comparison to svPPA patients. Results in svPPA patients suggest decreased functional connectivity along the ventral language pathway and increased functional connectivity along the dorsal language pathway. Finally, the observed connectivity patterns are overall consistent with previously reported structural connectivity and language profiles in these patients.
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The logopenic/phonological variant of primary progressive aphasia

The logopenic/phonological variant of primary progressive aphasia

WAB ⫽ Western Aphasia Battery; WAIS-III ⫽ Wechsler Adult Intelligence Scale, Third Edition. Since Mesulam’s original description of primary progressive aphasia (PPA) in 1982, 1 it has become clear that progressive isolated language disorders due to neurodegeneration are clini- cally heterogeneous. They are caused by patterns of localized cerebral dysfunction that do not necessarily match those affected “typically” by vascular strokes. Thus, the present-day distinc- tion between progressive nonfluent aphasia (PNFA) and semantic dementia (SemD) may re- flect an oversimplification of the clinical presentations of progressive aphasia. 2 In a recent
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The Brain Network of Naming: A Lesson from Primary Progressive Aphasia

The Brain Network of Naming: A Lesson from Primary Progressive Aphasia

Introduction Patients with primary progressive aphasia (PPA) usually report difficulty in word finding as the first and main complaint. Such difficulty, termed anomia, can manifest in both, spontane- ous speech or picture naming and is thought be the “single most common sign of PPA” [ 1 ]. According to language models, word finding is a multi-step process essentially involving access to the words’ semantics and subsequent lexical retrieval of the phonological code [ 2 ]. These two core steps appear to depend on anterior and posterior regions of the temporal cortex [ 3 – 5 ]. However, the use of various degenerative and vascular lesion models has led to divergent findings involving various temporal, parietal and frontal regions [ 6 ], thus resulting in an unsolved debate. In addition, several authors have suggested integrative brain regions, labeled ‘convergence zones’ [ 7 , 8 ], which might bind semantic and lexical information to ultimately form the basis for the phonological spell-out of articulated words. However, it is unclear whether there is a unique integrative hub underpinning one core operation, i.e. ‘binding’, and where such a hub might be localized. An important challenge is therefore to clarify the current situation with a single lesion model encompassing the entire language cortex with the aim of disentangling the core regions of naming and identifying a potential integrative hub. PPA rep- resents such a model providing a unique setting where the different components of the lan- guage network undergo progressive and selective dissolution related to neural degeneration. Unlike vascular models with stroke patients, which are anatomically restricted due to the blood vessel distribution [ 9 , 10 ], PPA affects the whole range of language-related cortical regions [ 11 – 13 ].
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Longitudinal gray matter contraction in three variants of primary progressive aphasia : a tensor-based morphometry study

Longitudinal gray matter contraction in three variants of primary progressive aphasia : a tensor-based morphometry study

782 ants of primary progressive aphasia. Ann. Neurol. 55 (3), 335–346. http://dx.doi.org/ 783 10.1002/ana.1082514991811. 784 Gorno-Tempini, M.L., Hillis, A.E., Weintraub, S., Kertesz, A., Mendez, M., Cappa, S.F., Ogar, J.M., 785 Rohrer, J.D., Black, S., Boeve, B.F., Manes, F., Dronkers, N.F., Vandenberghe, R., Rascovsky, 786 K., Patterson, K., Miller, B.L., Knopman, D.S., Hodges, J.R., Mesulam, M.M., Grossman, M.,

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Breakdowns in Informativeness of Naturalistic Speech Production in Primary Progressive Aphasia

Breakdowns in Informativeness of Naturalistic Speech Production in Primary Progressive Aphasia

Abstract: “Functional communication” refers to an individual’s ability to communicate effectively in his or her everyday environment, and thus is a paramount skill to monitor and target therapeutically in people with aphasia. However, traditional controlled-paradigm assessments commonly used in both research and clinical settings often fail to adequately capture this ability. In the current study, facets of functional communication were measured from picture-elicited speech samples from 70 individuals with mild primary progressive aphasia (PPA), including the three variants, and 31 age- matched controls. Building upon methods recently used by Berube et al. (2019), we measured the informativeness of speech by quantifying the content of each patient’s description that was relevant to a picture relative to the total amount of speech they produced. Importantly, form-based errors, such as mispronunciations of words, unusual word choices, or grammatical mistakes are not penalized in this approach. We found that the relative informativeness, or efficiency, of speech was preserved in non- fluent variant PPA patients as compared with controls, whereas the logopenic and semantic variant PPA patients produced significantly less informative output. Furthermore, reduced informativeness in the semantic variant is attributable to a lower production of content units and a propensity for self-referential tangents, whereas for the logopenic variant, a lower production of content units and relatively ”empty” speech and false starts contribute to this reduction. These findings demonstrate that functional communication impairment does not uniformly affect all the PPA variants and highlight the utility of naturalistic speech analysis for measuring the breakdown of functional communication in PPA.
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Structural, microstructural and metabolic alterations in Primary Progressive Aphasia variants

Structural, microstructural and metabolic alterations in Primary Progressive Aphasia variants

Mesulam, M. M., Thompson, C. K., Weintraub, S., Rogalski, E. J. (2015). The Wernicke conundrum and the anatomy of language comprehension in primary progressive aphasia. Brain, 138(8), 2423-2437. Matas-Guiu, J. A., Cabrera-Martn, M. N., P´erez-Castejn, M. J., Moreno-Ramos, T., Rodrguez-Rey, C., Garca-Ramos, R., Fernandez-Matarrubia, M., Oreja-Guevara, C., Matias-Guiu, J., Carreras, J. L. (2015). Visual and statistical analysis of 18F-FDG PET in primary progressive aphasia. European journal of nuclear medicine and molecular imaging, 42(6), 916-927.

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Naming unique entities in the semantic variant of primary progressive aphasia and Alzheimer's disease : Towards a better understanding of the semantic impairment

Naming unique entities in the semantic variant of primary progressive aphasia and Alzheimer's disease : Towards a better understanding of the semantic impairment

Abstract While the semantic variant of primary progressive aphasia (svPPA) is characterized by a predominant semantic memory impairment, episodic memory impairments are the clinical hallmark of Alzheimer’s disease (AD). However, AD patients also present with semantic deficits, which are more severe for semantically unique entities (e.g. a famous person) than for common concepts (e.g. a beaver). Previous studies in these patient populations have largely focused on famous-person naming. Therefore, we aimed to evaluate if these impairments also extend to other semantically unique entities such as famous places and famous logos. In this study, 13 AD patients, 9 svPPA patients, and 12 cognitively unimpaired elderly subjects (CTRL) were tested with a picture-naming test of non-unique entities (Boston Naming Test) and three experimental tests of semantically unique entities assessing naming of famous persons, places, and logos. Both clinical groups were overall more impaired at naming semantically unique entities than non-unique entities. Naming impairments in AD and svPPA extended to the other types of semantically unique entities, since a CTRL > AD > svPPA pattern was found on the performance of all naming tests. Naming famous places and famous persons appeared to be most impaired in svPPA, and both specific and general semantic knowledge for these entities were affected in these patients. Although AD patients were most significantly impaired on famous-person naming, only their specific semantic knowledge was impaired, while general knowledge was preserved. Post-hoc neuroimaging analyses also showed that famous-person naming impairments in AD correlated with atrophy in the temporo-parietal junction, a region functionally associated with lexical access. In line with previous studies, svPPA patients’ impairment in both naming and semantic knowledge suggest a more profound semantic impairment, while naming impairments in AD may arise to a greater extent from impaired lexical access, even though semantic impairment for specific knowledge is also present. These results highlight the critical importance of developing and using a variety of semantically-unique-entity naming tests in neuropsychological assessments of patients with neurodegenerative diseases, which may unveil different patterns of lexical- semantic deficits.
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The Nonverbal Processing of Actions Is an Area of Relative Strength in the Semantic Variant of Primary Progressive Aphasia

The Nonverbal Processing of Actions Is an Area of Relative Strength in the Semantic Variant of Primary Progressive Aphasia

of nouns, while actions typically belong to the category of verbs. Verbs have long been considered more difficult to process than nouns because they have complex, highly context-dependent meanings (Druks et al., 2006; Kim & Thompson, 2004; Szekely et al., 2005; Vigliocco et al., 2011). Furthermore, verbs and nouns differ in their mor- phosyntactic properties. Verbs have different argument structures that determine the number and type of com- plements they can take and influence their lexical access (Kim & Thompson, 2004; Thompson et al., 2012). They also have different inflected forms that mark grammatical information such as tense, mode, person, and number. Nouns have simpler morphosyntactic properties but can carry grammatical gender information and be inflected for number, for example (Levelt, 1989). Thompson et al. (2012) tested patients with different profiles of aphasia resulting from stroke and PPA variants on noun and verb production and comprehension. Nouns were better pre- served than verbs in patients with agrammatic aphasia resulting from stroke and patients with nonfluent/agrammatic PPA. This effect was found in word production but not in word comprehension. They also found a transitivity (argument structure) effect in patients with agrammatic aphasia resulting from stroke and nonfluent/agrammatic PPA who produced one-argument verbs more accurately than two- or three-argument verbs. In comparison, three out of the four patients with svPPA had a better perfor- mance for verbs than nouns in both production and com- prehension. There was no transitivity effect for verb production or comprehension in svPPA. The study of Thompson et al. shows that the contrast between nouns and verbs (or objects and actions) is best interpreted in the light of the patients ’ overall language profile. In patients with syntactic and grammatical impairments, the compari- son reveals differences in words ’ morphosyntactic proper- ties. In patients with semantic impairments, differences in the relative importance of various sets of semantic features for the words ’ representation are highlighted. It is worth noting that, if the effect was driven by the complexity of semantic representations and existence of multiple, context- dependent meanings for actions/verbs, a better preservation of objects/nouns would be expected in svPPA (Druks et al., 2006; Kim & Thompson, 2004). Instead, the pattern re- ported in this study and others point toward the importance of different semantic features in the representation of these categories of content (Vigliocco et al., 2011).
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Comprehension of concrete and abstract words in semantic variant primary progressive aphasia and Alzheimer’s disease: a behavioral and neuroimaging study

Comprehension of concrete and abstract words in semantic variant primary progressive aphasia and Alzheimer’s disease: a behavioral and neuroimaging study

The lesion study also showed that patients with lesions in the left temporoparietal cortex (TPC), including the AG, had specific difficulty discerning the meaning of[r]

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Deformation-based shape analysis of the hippocampus in the semantic variant of primary progressive aphasia and Alzheimer’s disease

Deformation-based shape analysis of the hippocampus in the semantic variant of primary progressive aphasia and Alzheimer’s disease

in AD. These results seem to contradict the hypothesis that the bilateral hippocampus would be damaged in AD, and only the left one in svPPA ( Chan et al., 2001; Galton et al., 2001 ). In fact, although the lateral anterior temporal lobes changes are usually asymmetrical, mainly af- fecting the left hemisphere, the hippocampal morphological changes seem to affect both the left and right hippocampus, even at mild stages of the disease. Shape differences in the left hippocampus, similar to those found in our study, were previously reported. However, in this study, shape differences in the right hippocampus did not survive False Discovery Rate (FDR) correction ( Lindberg et al., 2012 ). This difference in the results can be due to the smaller sample size used in this study. It must be noted that the fact that we observed bilateral shape differences does not exclude the hypothesis that the primary site of pathology in svPPA is in the left hemisphere, and then spreading to the right one. In fact, the present study does not allow determining the evolution of morphological changes over time. Longitudinal studies in a large sample of patients are necessary to better determine the time course of the hippocampal morphological damage in svPPA.
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Clinical, anatomical and pathological features in the three variants of primary progressive aphasia : a review

Clinical, anatomical and pathological features in the three variants of primary progressive aphasia : a review

Gériatrie de Montréal, Montréal, QC, Canada, 3 Département de Psychologie, Université de Montréal, Montréal, QC, Canada, 4 Memory and Aging Center, University of California at San Francisco, San Francisco, CA, United States, 5 Department of Neurology, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A), Paris, France Primary progressive aphasias (PPA) are neurodegenerative diseases clinically characterized by an early and relatively isolated language impairment. Three main clinical variants, namely the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA) have been described, each with specific linguistic/cognitive deficits, corresponding anatomical and most probable pathological features. Since the discovery and the development of diagnostic criteria for the PPA variants by the experts in the field, significant progress has been made in the understanding of these diseases. This review aims to provide an overview of the literature on each of the PPA variant in terms of their clinical, anatomical and pathological features, with a specific focus on recent findings. In terms of clinical advancements, recent studies have allowed a better characterization and differentiation of PPA patients based on both their linguistic and non-linguistic profiles. In terms of neuroimaging, techniques such as diffusion imaging and resting-state fMRI have allowed a deeper understanding of the impact of PPA on structural and functional connectivity alterations beyond the well-defined pattern of regional gray matter atrophy. Finally, in terms of pathology, despite significant advances, clinico-pathological correspondence in PPA remains far from absolute. Nonetheless, the improved characterization of PPA has the potential to have a positive impact on the management of patients. Improved reliability of diagnoses and the development of reliable in vivo biomarkers for underlying neuropathology will also be increasingly important in the future as trials for etiology-specific treatments become available.
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en fr Multimodal brain imaging for the study of progressive primary aphasia Imagerie cérébrale multimodale pour l'étude des aphasies primaires progressives

Caractérisation en imagerie multimodale des APP 4.2 Article (en anglais) 4.2.1 Introduction Primary Progressive Aphasia (PPA) is a group of neurodegenerative diseases affecting lan- guage abilities. PPA have been classified intro three main variants (Gorno-Tempini et al., 2011): the semantic variant (sv-PPA) characterized by the impairment of the representations of word meanings, the logopenic variant (lv-PPA) surfacing with lexical disorder and a de- crease of verbal short-term memory, and the non-fluent/agrammatic variant (nfv-PPA) char- acterized by phonological/phonetic and syntactic disorders. Several neuroimaging studies have explored the brain alterations in the three PPA variants. Cortical atrophy in sv-PPA is located in anterior temporal lobes with left predominance (Acosta-Cabronero et al., 2011; Gorno-Tempini et al., 2004; Mack et al., 2015; Rohrer et al., 2012), and metabolic alterations of the cortex on FDG-PET usually overlap with these temporal regions (Acosta-Cabronero et al., 2011; Moodley et al., 2015). White matter damage involves the uncinate fasciculus and the inferior longitudinal fasciculus bilaterally (Galantucci et al., 2011; Mahoney et al., 2013). One study also found alterations of the left arcuate fasciculus and the left inferior fronto-occipital fasciculus (Mandelli et al., 2014). Lv-PPA is associated with cortical atrophy of the left temporo-parietal junction (Gorno-Tempini et al., 2004) extending in some studies to more anterior temporal regions (Cerami et al., 2017; Ossenkoppele et al., 2015; Spinelli et al., 2017; Whitwell et al., 2015). Hypometabolism is observed in the left temporo-parietal junction, and in left inferior, middle and superior-posterior temporal cortices (Cerami et al., 2017), which, in some studies, can extend to left prefrontal regions and to the right hemi- sphere (Lehmann et al., 2013; Madhavan et al., 2013; Whitwell et al., 2015). White matter alterations involve the left arcuate fasciculus/superior longitudinal fasciculus (Galantucci et al., 2011; Mahoney et al., 2013) and the left inferior longitudinal fasciculus (Mandelli et al., 2014). Nfv-PPA patients exhibit atrophy in left frontal regions although specific anatomical areas vary from study to study (Botha et al., 2015; Mesulam et al., 2012; Rohrer et al., 2012). Hypometabolism is found in the inferior frontal gyrus, the middle frontal gyrus and in the supplementary motor area (Cerami et al., 2017; Matías-Guiu et al., 2015b). White matter alterations involve the left superior longitudinal fasciculus (Galantucci et al., 2011). Involvement of the left uncinate fasciculus (Mahoney et al., 2013), the frontal aslant tract (Catani et al., 2013) or the left inferior frontal-occipital fasciculus (Mandelli et al., 2014) has also been described.
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Anatomical correlates of early mutism in progressive nonfluent aphasia

Anatomical correlates of early mutism in progressive nonfluent aphasia

NEUROLOGY 2006;67:1849–1851 M.L. Gorno-Tempini, MD, PhD; J.M. Ogar, MS; S.M. Brambati, PhD; P. Wang, MD; J.H. Jeong, MD; K.P. Rankin, PhD; N.F. Dronkers, PhD; and B.L. Miller, MD Primary progressive aphasia (PPA) is characterized by speech and language deficits that remain isolated for at least 2 years. 1 Once thought a unitary syn- drome, PPA is now typically divided into variants. 2,3 . Progressive nonfluent aphasia (PNFA) is character- ized by effortful speech, agrammatism in production and comprehension, with preserved single word com- prehension. It has been shown that apraxia of speech (AOS) is the most common motor speech deficit in PNFA. 2
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Adaptation du Bilingual Aphasia Test (Version Courte) au libanais : Données linguistiques et psychométriques

Adaptation du Bilingual Aphasia Test (Version Courte) au libanais : Données linguistiques et psychométriques

Outre son usage habituel, le BAT a fait l’objet d’autres usages 18 (Paradis, 2011) : usage clinique, expérimental avec des sujets sains ou présentant diverses pathologies du langage (aphasie trouble spécifique du langage, maladie d’Alzheimer, maladie de Parkinson, autisme, etc. Gómez- Ruiz et Aguilar-Alonso (2011) ont trouvé que la version catalan-espagnol du BAT permet de distinguer entre sujet bilingues sains, avec trouble cognitif modéré et la maladie d’Alzheimer. Cependant, certaines erreurs de classification entre ces groupes peuvent être dues à un niveau éducatif bas ou à un bilinguisme tardif. Les épreuves sensibles à la classification sont les épreuves lexicales telle que la fluence verbale et les automatismes ainsi que les épreuves de compréhension orale telles que l’acceptabilité sémantique, la décision lexicale et la compréhension orale, les épreuves métalinguistiques (jugement grammatical et morphologie dérivationnelle) et la description d’images. De même, Kambanaros et Grohmann (2012) ont réalisé une étude de cas sur un patient trilingue qui présente une aphasie primaire progressive (APP). L’évaluation de ses trois langues par le biais du BAT a permis de trancher le type de son APP. Le BAT permet également
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Are Progressive Fiscal Rules Stabilizing?

Are Progressive Fiscal Rules Stabilizing?

Our results are formalized within two benchmark models and show how the efficiency of progressive fiscal schemes as local automatic stabilizers depends on the fiscal base. In the first setting with heterogeneous agents and segmented asset markets in which wage income mostly finances consumption, we show that progressive taxes and transfers should be made dependent on labor income, so as to rule out local indeterminacy. On the contrary, progressive fiscal rules should be applied to capital income in an overlapping generations economy where consumption comes from savings income. Incidentally, the latter results suggest that capital income taxes may be desirable, when progressive, to make local expectation-driven fluctuations less likely. In both frameworks, key to the results is the property that progressive fiscal rules provide insurance in the presence of imperfect capital markets.
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Regional projects : towards progressive collaboration

Regional projects : towards progressive collaboration

towards progressive collaboration 3 Discussing the proceedings of a Technical Advisory Committee (TAC) for an agriculture project in the Caribbean probably sounds like a dry subject. It conjures up images of bureaucrats sitting around a table discussing policy and plans, hashing out process and determining progress. Frankly, that pretty much sums up the TAC for the Agricultural Policy Programme (APP) which took place in Port of Spain, Trinidad and Tobago on 11 and 12 August, 2016. However, if one considers the history of agriculture development projects in the Caribbean, this particular picture becomes quite exciting. It is not that the meetings and topics were unusual, but rather the mix of company.
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L'inclusion progressive du référendum local en Europe

L'inclusion progressive du référendum local en Europe

Si un référendum est organisé à la suite de cette initiative, alors nous sommes en présence d’un référendum d’initiative populaire, élément considéré comme étant [r]

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L'Égyptologie : du repli sur soi à l'ouverture, une mutation progressive

L'Égyptologie : du repli sur soi à l'ouverture, une mutation progressive

Depuis la seconde moitié du XX e s., on assiste à une progressive ouverture de l’Égyptologie aux autres disciplines des sciences humaines et sociales. Cela s’illustre de plusieurs manières. La plus importante est l’apparition de plus en plus d’ouvrages collectifs associant Égyptologues et spécialistes de ces disciplines : K.R. Weeks (éd.), Egyptology and Social Sciences (1979) ; J. Lustig (éd.), Anthropology and Egyptology (1997) ; A. Verbovsek, B. Backes et C. Jones (éd.), Methodik und Didaktik in der Ägyptologie (2011), etc. 17 Ces publications ont pour but d’extraire l’Egyptologie de son isolement et de permettre des échanges constructifs entre chercheurs. Par exemple, en introduction de son livre Anthropology and Egyptology, J. Lustig indique son objectif : « to demonstrate how anthropology and Egyptology can combine for innovative and productive purposes ». 18
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