International recommendations on the diagnosis and treatment of patients with acquired hemophilia A.

Acquired hemophilia A (AHA) is a rare bleeding disorder characterized by autoantibodies directed against circulating coagulation factor (F) VIII. Typically, patients with no prior history of a bleeding disorder present with spontaneous bleeding and an isolated prolonged aPTT. AHA may, however, present without any bleeding symptoms, therefore an isolated prolonged aPTT should always be investigated further irrespective of the clinical findings. Control of acute bleeding is the first priority, and we recommend first-line therapy with bypassing agents such as recombinant activated FVII or activated prothrombin complex concentrate. Once the diagnosis has been achieved, immediate autoantibody eradication to reduce subsequent bleeding risk should be performed. We recommend initial treatment with corticosteroids or combination therapy with corticosteroids and cyclophosphamide and suggest second-line therapy with rituximab if first-line therapy fails or is contraindicated. In contrast to congenital hemophilia, no comparative studies exist to support treatment recommendations for patients with AHA, therefore treatment guidance must rely on the expertise and clinical experience of specialists in the field. The aim of this document is to provide a set of international practice guidelines based on our collective clinical experience in treating patients with AHA and contribute to improved care for this patient group.

A study of the translational regulation exerted by some neuroactive substances on the expression of the monocarboxylate transporter MCT2 in cultured cortical neurons

Summary of the thesis Glucose has been considered the major, if not the exclusive, energy substrate for the brain. But under certain conditions other substrates, namely monocarboxylates (lactate, pyruvate, and ketone bodies), can contribute significantly to satisfy brain energy demands. These monocarboxylates need to be transported across the blood brain barrier as well as out of astrocytes into the extracellular space and taken up into neurons. It has been shown that monocarboxylates are transported by a family of proton-linked transporters called monocarboxylate transporters (MCTs). In the central nervous system, MCT2 is the predominant neuronal form and little is known about the regulation of its expression. The neurotransmitter noradrenaline (NA) was shown previously to enhance the expression of MCT2 in cultured cortical neurons via a translational mechanism. Here, we demonstrate that two other substances, namely, insulin and IGF-1 enhance MCT2 protein expression in cultured mouse cortical neurons in a time- and concentrationdependent manner without affecting MCT2 mRNA levels. This result confirmed that MCT2 protein expression is translationally regulated and extend the observation to different types of neuroactive substances. Then we sought to determine by which signaling pathway(s) NA, insulin and IGF-1 can induce MCT2 protein expression. First, we observed by Western blot that all three substances cause activation of the MAP kinase ERK as well as the kinase Akt via their phosphorylation. Moreover, the mTOR/S6K pathway which is known to play an important role in translation initiation regulation was also strongly stimulated by all three substances. Second, we sought to determine the implication of these signaling pathways on the NA-, insulin- and IGF-1-induced enhancement of MCT2 protein expression and used specific inhibitors of these signaling pathways. We observed that the Pia kinase and mTOR inhibitors LY294002 and rapamycin respectively, strongly prevent the enhancement. of MCT2 expression caused by either NA, insulin ar IGF-1. In contrast, the MEK inhibitor PD98059 and the p38 MAP kinase inhibitor SB202190 had only a slight effect on the enhancement of MCT2 expression in all three cases. These results suggest that NA, insulin and IGF-1 regulate MCT2 protein expression by a common mechanism most likely involving the Akt/PKB pathway and translational activation via mTOR. In conclusion, considering the roles of NA, insulin and IGF-1 in synaptic plasticity, the tight translational regulation of MCT2 expression by these substances may represent a common mechanism through which supply of potentiated synapses with nonglucose energy substrates can be adapted to the level of activity. Résumé du travail de thèse Le glucose représente le substrat énergétique majeur pour le cerveau. Cependant, dans certaines conditions physiologiques ou pathologiques, le cerveau a la capacité d'utiliser des substrats énergétiques appartenant à la classe des monocarboxylates (lactate, pyruvate et corps cétoniques) afin de satisfaire ses besoins énergétiques. Ces monocarboxylates doivent être transportés à travers la barrière hématoencéphalique mais aussi hors des astrocytes vers l'espace extracellulaire puis re-captés par les neurones. Leur transport est assuré par une famille de transporteurs spécifiques, protons-dépendants, appelés transporteurs aux monocarboxylates (MCTs). Dans le système nerveux central, les neurones expriment principalement l'isoforme MCT2 mais peu d'informations sont disponibles concernant la régulation de son expression. Il a été montré que le neurotransmetteur noradrénaline (NA) augmente l'expression de MCT2 dans les cultures de neurones corticaux de souris par le biais d'un mécanisme de régulation traductionnel. La présente étude nous a permis de démontrer que deux autres substances, l'insuline et 17GF-1, induisent une augmentation de la protéine MCT2 dans ces mêmes cultures selon un décours temporel et une gamme de concentrations particulière. Etonnamment, aucun changement n'a été observé concernant les niveaux d'ARNm de MCT2. Ce résultat .confirme que la protéine MCT2 est régulée de manière traductionnelle et révèle que différentes substances neuro-actives peuvent réguler l'expression de MCT2. Compte tenu de ces observations, nous avons voulu déterminer par quelle(s) voie(s) de signalisation la NA, l'insuline et l'IGF-1 exercent leur effet sur l'expression de MCT2. Dans un premier temps, nous avons pu observer par Western blot que ces trois substances activent la MAP kinase ERK ainsi que la kinase Akt via leur phasphorylation. De plus, la voie mTOR/S6K, connue pour son implication dans la régulation de l'initiation de la traduction est aussi fortement activée par ces trois substances. Dans un second temps, nous avons voulu déterminer I implication de chacune de ces voies de signalisation dans l'augmentation de l'expression de la protéine MCT2 observée après stimulation à la NA, à l'insuline et à l'IGF-1. Pour ce faire, nous avons utilisé des inhibiteurs spécifiques de chacune de ces voies. (Vous avons observé que les inhibiteurs des voies PI3 kinase et mTOR (LY294002 et rapamycin respectivement), prévenaient fortement l'augmentation de l'expression de MCT2 induite par la NA, l'insuline ou (IGF-1. A l'inverse, les inhibitions de la MAP kinase .kinase MEK ainsi que de la MAP kinase p38 (par l'utilisation des inhibiteurs spécifiques PD98059 et SB202190 respectivement) n'ont eu qu'un léger effet dans ces mêmes conditions. Ces résultats suggèrent que la NA, 'l'insuline et I~GF-1 régulent l'expression de la protéine MCT2 par un mécanisme commun impliquant probablement la voie Akt/PKB et l'activation de la traduction via mTOR. En conclusion, considérant l'implication de la NA, de l'insuline et de I`IGF-1 dans la plasticité synaptique, le contrôle traductionnel étroit exercé par ces substances sur l'expression de MCT2 pourrait être un moyen d'alimenter en substrats énergétiques autres que le glucose les synapses activées et également d'adapter l'approvisionnement en substrats énergétiques au niveau d'activité. Résumé « grand public » Le cerveau est un organe qui réalise des tâches complexes nécessitant un apport important en énergie. La principale source d'énergie du cerveau est le glucose. Bien que le cerveau ne représente que 2% de la masse corporelle, il consomme à lui seul plus de 25% du glucose et 20% de l'oxygène provenant de la circulation sanguine. La nécessité d'un tel apport en énergie réside dans la nature -même du fonctionnement des milliards de neurones qui utilisent des signaux électriques et chimiques pour communiquer entre eux. Hormis l'utilisation massive du glucose comme source d'énergie, le cerveau est capable de consommer d'autres substrats énergétiques dans certaines conditions physiologiques ou pathologiques. Les monocarboxylates (lactate, pyruvate et corps cétoniques) font partie de ces autres sources d'énergie. Contrairement au glucose, les monocarboxylates ne diffusent pas facilement de la circulation sanguine vers les neurones. Afin de pouvoir être consommés par les neurones, ils doivent être transportés par un système adapté. Ce sont des transporteurs appelés transporteurs aux monocarboxylates ou MCT qui permettent le passage de ces substrats énergétiques du sang vers les neurones. Le but de ce travail de thèse a été de comprendre comment est régulée l'expression de MCT2, l'un de ces transporteurs exprimé spécifiquement à la surface des neurones. Cette étude nous a permis de mettre en évidence que le neurotransmetteur noradrénaline ainsi que les hormones insuline et IGF-1 (insulinlike growth factor-1) sont capables d'induire une augmentation d'expression de MCT2 à la surface des neurones en culture. Nous avons ensuite voulu déterminer par quels mécanismes de signalisation ces substances agissent sur l'expression de MCT2. Nous avons pu observer que la surexpression de la protéine MCT2 est due à une augmentation d'activité traductionnelle (la traduction étant une des étapes qui permet la synthèse des protéines) induite par le biais d'une voie de signalisation particulière. En conclusion, lorsque la noradrénaline, l'insuline ou 17GF-1 agissent sur les neurones, la traduction de la protéine MCT2 est activée et on observe une augmentation de l'expression de MCT2. Ce mécanisme pourrait permettre d'augmenter l'apport énergétique au niveau des neurones en augmentant le nombre de transporteurs pour les substrats énergétiques que sont les monocarboxylates. D'un point de vue physiologique, cette régulation d'expression pourrait jouer un rôle primordial dans des situations d'apprentissage et de mémorisation. Sur le plan pathologique, cela pourrait permettre de prévenir les dommages causes aux neurones dans certains cas d'atteintes cérébrales.

No major impact of skin aging on the response of skin blood flow to a submaximal local thermal stimulus

La peau est sujette à un vieillissement intrinsèque (processus naturel et chronologique) et extrinsèque (processus induit par l'environnement et notamment les rayons UV). Plusieurs études ont montré que le vieillissement cutané s'accompagne d'une réduction de la densité capillaire au sein du derme et d'une dégradation de plusieurs protéines de la matrice extracellulaire. Cette atteinte morphologique est associée à une diminution de la capacité vasodilatatrice maximale de la microcirculation dermique et en particulier, de la réponse maximale du flux sanguin cutané à un échauffement local de la surface cutanée à des températures avoisinant les 43-44°C. Cette réponse, appelée hyperémie locale induite par la chaleur (local thermal hyperemia), est facilement mesurable par des investigations non invasives, telles que le laser Doppler. Nous avons entrepris cette étude afin d'investiguer les effets de l'âge sur la réactivité de la microcirculation dermique dans des zones cutanées exposées différemment aux rayons UV. Pour ce faire, nous avons étudié, chez des patients jeunes (18 à 30 ans, n=13) et des patients âgés (> 60 ans, n=13), la vasodilatation cutanée induite par réchauffement local de la peau, au niveau de 3 sites anatomiques différents (la cuisse, l'avant- bras et le front). Les mesures ont été effectuées au moyen d'un laser Doppler. Pour chaque sujet et chaque site, la température cutanée fut tout d'abord amenée à 34°C par 2 corps de chauffe (A et B), disposés de manière adjacente sur la peau. La température fut ensuite augmentée à 39°C (corps de chauffe A) et à 41°C (corps de chauffe B) pour une durée de 30 minutes, dans l'optique d'induire une vasodilatation sous- maximale. Ensuite, la température fut augmentée à 43 °C (corps de chauffe A et B) pour 15 minutes supplémentaires. Enfin, la vasodilatation maximale a été induite par un échauffement local à 44°C pour 15 minutes supplémentaires (corps de chauffe A et B). L'enregistrement séquentiel du flux sanguin cutané, effectué chaque minute par laser Doppler imager, donne des images sur lesquelles peut être calculé le flux sanguin cutané (unités de perfusion, PU). Par la suite, nous avons calculé les conductances vasculaires cutanées (CVC), en divisant le flux sanguin (PU) par la tension artérielle moyenne (mmHg), afin de permettre une normalisation entre les différents sujets. Les CVC, évaluées au temps de départ (température 34°C) et après vasodilatation maximale (température 44°C), étaient plus hautes au niveau du front qu'au niveau des 2 autres sites anatomiques. Sur les 3 sites, la CVC maximale (température 44°C) diminuait avec l'âge mais de façon moins importante au niveau du front, en comparaison avec les 2 autres sites. La réponse aux températures sous-maximales (température 39 et 41°C), exprimée en pourcentage de la CVC maximale, ne variait pas avec l'âge ni en fonction du site anatomique étudié. En conclusion, cette étude est la première à étudier simultanément l'hyperémie locale induite par la chaleur sur 3 sites ayant une exposition différente aux rayons UV. Le processus utilisé (laser Doppler imager) est également unique dans la littérature concernant les altérations de la microcirculation cutanée en lien avec l'âge. Cette étude confirme ainsi que le vieillissement cutané intrinsèque et/ou extrinsèque réduit la capacité vasodilatatrice maximale de la microcirculation dermique. Par contre, la réactivité à réchauffement local à des températures moindres ne semble pas être affectée.

The Emergence and Governance of Euroregions: The Case of the Euregio on the Dutch-German Border

Amb una història que data de la dècada de 1950, la EUREGIO és un de les més antigues euroregions a Europa. Es pot considerar com un cas exitós d'una regió transfronterera (CBR) en el sentit que s'ha establert fermament com una agència de fronteres dins del seu tram de la frontera holandesa-alemanya. L'EUREGIO també ha estat una de les protagonistes principals darrere de l'Associació de Regions Frontereres Europees (ARFE), que en les últimes dècades va actuar per difondre el model d'euroregió a tot el territori europeu. Aquest capítol té diversos objectius. En primer lloc, es presenta el cas de la EUREGIO i presenta evidència sobre la seva història, estructura orgànica i polítiques. En segon lloc, s'analitzen les condicions del context en què la EUREGIO ha sorgit i les estructures de govern que es van crear com a resultat. Es fa especial èmfasi en la posició i el paper de l'Euroregió en el context més ampli del marc de governança europea multinivell generat per la política de cohesió de la UE. El capítol conclou amb un intent d'avaluar l'èxit i l'impacte de la EUREGIO i una discussió dels reptes relacionats amb la doble funció de l'EUREGIO com a representant dels interessos de les autoritats locals i les agències de cohesió de la UE posada en pràctica de les polítiques.

Results from a multicentre international registry of familial Mediterranean fever: impact of environment on the expression of a monogenic disease in children.

BACKGROUND AND AIM: Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations of the MEFV gene. We analyse the impact of ethnic, environmental and genetic factors on the severity of disease presentation in a large international registry. METHODS: Demographic, genetic and clinical data from validated paediatric FMF patients enrolled in the Eurofever registry were analysed. Three subgroups were considered: (i) patients living in the eastern Mediterranean countries; (ii) patients with an eastern Mediterranean ancestry living in western Europe; (iii) Caucasian patients living in western European countries. A score for disease severity at presentation was elaborated. RESULTS: Since November 2009, 346 FMF paediatric patients were enrolled in the Eurofever registry. The genetic and demographic features (ethnicity, age of onset, age at diagnosis) were similar among eastern Mediterranean patients whether they lived in their countries or western European countries. European patients had a lower frequency of the high penetrance M694V mutation and a significant delay of diagnosis (p<0.002). Patients living in eastern Mediterranean countries had a higher frequency of fever episodes/year and more frequent arthritis, pericarditis, chest pain, abdominal pain and vomiting compared to the other two groups. Multivariate analysis showed that the variables independently associated with severity of disease presentation were country of residence, presence of M694V mutation and positive family history. CONCLUSIONS: Eastern Mediterranean FMF patients have a milder disease phenotype once they migrate to Europe, reflecting the effect of environment on the expression of a monogenic disease.

Keratotic Nodule on The Heel: A Quiz.

A 51-year-old man, with a medical history of medullary thyroid carcinoma excised under thyroxine treatment presented with a painful enlarging lesion on his right heel since one year. A 3-cm diameter, greyish, infiltrated nodule with spicules was seen on physical examination (Fig. 1a). A 5-mm surgical excision was made and a total skin graft was used for reconstruction. Histopathology of the total resected tumour revealed pseudoepitheliomatous hyperplasic epidermis and a proliferation located between rete ridges, dermis and superficial hypodermis (Fig. 1b). The proliferation was composed of nets and cordons of cells with granular and abundant PAS-positive cytoplasm. Immunostains showed cytoplasmic positivity for s100 and inhibin (Fig. 1c). Three years later the patient is asymptomatic.

Alpine tectonic evolution of a Jurassic subduction-accretionary complex: Deformation, kinematics and 40Ar/39Ar age constraints on the Mesozoic low-grade schists of the Circum-Rhodope Belt in the eastern Rhodope-Thrace region, Bulgaria-Greece

Deformation of the Circum-Rhodope Belt Mesozoic (Middle Triassic to earliest Lower Cretaceous) low-grade schists underneath an arc-related ophiolitic magmatic suite and associated sedimentary successions in the eastern Rhodope-Thrace region occurred as a two-episode tectonic process: (i) Late Jurassic deformation of arc to margin units resulting from the eastern Rhodope-Evros arc-Rhodope terrane continental margin collision and accretion to that margin, and (ii) Middle Eocene deformation related to the Tertiary crustal extension and final collision resulting in the closure of the Vardar ocean south of the Rhodope terrane. The first deformational event D-1 is expressed by Late Jurassic NW-N vergent fold generations and the main and subsidiary planar-linear structures. Although overprinting, these structural elements depict uniform bulk north-directed thrust kinematics and are geometrically compatible with the increments of progressive deformation that develops in same greenschist-facies metamorphic grade. It followed the Early-Middle Jurassic magmatic evolution of the eastern Rhodope-Evros arc established on the upper plate of the southward subducting Maliac-Meliata oceanic lithosphere that established the Vardar Ocean in a supra-subduction back-arc setting. This first event resulted in the thrust-related tectonic emplacement of the Mesozoic schists in a supra-crustal level onto the Rhodope continental margin. This Late Jurassic-Early Cretaceous tectonic event related to N-vergent Balkan orogeny is well-constrained by geochronological data and traced at a regional-scale within distinct units of the Carpatho-Balkan Belt. Following subduction reversal towards the north whereby the Vardar Ocean was subducted beneath the Rhodope margin by latest Cretaceous times, the low-grade schists aquired a new position in the upper plate, and hence, the Mesozoic schists are lacking the Cretaceous S-directed tectono-metamorphic episode whose effects are widespread in the underlying high-grade basement. The subduction of the remnant Vardar Ocean located behind the colliding arc since the middle Cretaceous was responsible for its ultimate closure, Early Tertiary collision with the Pelagonian block and extension in the region caused the extensional collapse related to the second deformational event D-2. This extensional episode was experienced passively by the Mesozoic schists located in the hanging wall of the extensional detachments in Eocene times. It resulted in NE-SW oriented open folds representing corrugation antiforms of the extensional detachment surfaces, brittle faulting and burial history beneath thick Eocene sediments as indicated by 42.1-39.7 Ma Ar-40/Ar-39 mica plateau ages obtained in the study. The results provide structural constraints for the involvement components of Jurassic paleo-subduction zone in a Late Jurassic arc-continental margin collisional history that contributed to accretion-related crustal growth of the Rhodope terrane. (C) 2011 Elsevier Ltd. All rights reserved.

Influence of the primary cleft palate closure on the future need for orthognathic surgery in unilateral cleft lip and palate patients

RESUME : Introduction : L'objectif de cette étude est de déterminer l'influence de la dissection du palais lors de la chirurgie primaire et le type de chirurgie orthognathique requise chez les patients porteurs d'une séquelle de fente labio-maxillo-palatine unilatérale complète Méthode : Cette revue porte sur 58 enfants nés avec une fente labio-maxillo-palatine complète unilatérale et traités entre 1994 et 2008 à Page approprié pour une chirurgie orthognathique. C'est une étude rétrospective longitudinale mixte. Les patients avec des syndromes ou anomalies associées ont été exclus. Tous les patients ont été traités parle même orthodontiste et par la même équipe chirurgicale. Les enfants sont divisés en deux groupes; le premier comprend les patients avec une chirurgie primaire du palais conventionnelle, avec un décollement extensif de la fibro-muqueuse palatine. Le deuxième groupe comprend les patients opérés selon le protocole de Malek. Le palais mou est fermé a |'âge de trois mois, le palais dur à |'âge de six mois, avec un décollement minimal de la tibro-muqueuse palatine. Les radiographies du crâne de profil ainsi que les données chirurgicales ont été comparées. Résultats: La nécessité d'une chirurgie orthognathique est plus élevée dans le premier groupe par rapport au deuxième (60% versus 47,8%). Concernant le type de chirurgie orthognathique réalisé, des ostéotomies Lefort I en deux ou trois pièces ou des ostéotomies bi-maxillaires ont aussi été plus fréquentes dans le premier groupe Conclusion : La chirurgie primaire du palais selon le protocole de Malek améliore le pronostic des patients avec une fente labio-maxillo-palatine. Avec un décollement minimal de la fibro-muqueuse palatine, le nombre d'interventions de chirurgie orthognathique a été diminué. Lorsque ces opérations étaient néanmoins indiquées, elles étaient simplifiées.

Little Dairy on the Prairie: from butter makin' to high-tech agriculture, 2005

In 2001, extensive archaeological excavations were conducted at the Oneida Cheese Factory in Jones County. The county is a microcosm of larger dairying trends found throughout northeast Iowa, the state’s premier dairy-producing region. Jones County moved from homemade cheese and butter production by farm women, to the industrialization of the dairy farm and opening of cheese factories and butter creameries. A number of innovations affected the industry around the turn-of-the-twentieth century, including reliable butterfat testing, the introduction of ensilage (silos) that created yearround milk production, and consolidation of the many local creameries into larger creamery organizations, such as the Diamond Creamery run by Henry D. Sherman of Jones County. Iowa’s dairy industry of today looks very different from its heritage: consolidation and competition have drastically reduced the number of cows, dairy farms, and processing plants. In recent years, northeast Iowa has become the center of a movement to revitalize Iowa’s dairy industry, particularly through the use of value-added strategies, such as niche markets and large regional co-operatives: the lessons from Iowa’s dairying legacy are resurfacing as a solution to modern agricultural challenges.

Clients of sex workers in Switzerland: it makes sense to counsel and propose rapid test for HIV on the street, a preliminary report.

BACKGROUND: Clients of street sex workers may be at higher risk for HIV infection than the general population. Furthermore, there is a lack of knowledge regarding HIV testing of clients of sex workers in developed countries. METHOD: This pilot study assessed the feasibility and acceptance of rapid HIV testing by the clients of street-based sex workers in Lausanne, Switzerland. For 5 evenings, clients in cars were stopped by trained field staff for face-to-face interviews focusing on sex-related HIV risk behaviors and HIV testing history. The clients were then offered a free anonymous rapid HIV test in a bus parked nearby. Rapid HIV testing and counselling were performed by experienced nurse practitioners. Clients with reactive tests were offered confirmatory testing, medical evaluation, and care in our HIV clinic. RESULT: We intercepted 144 men, 112 (77.8%) agreed to be interviewed. Among them, 50 (46.6%) had never been tested for HIV. A total of 31 (27.7%) rapid HIV tests were performed, 16 (51.6%) in clients who had not previously been tested. None were reactive. Initially, 19 (16.9%) additional clients agreed to HIV testing but later declined due to the 40-minute queue for testing. CONCLUSION: This pilot study showed that rapid HIV testing in the red light district of Lausanne was feasible, and that the clients of sex workers accepted testing at an unexpectedly high rate. This setting seems particularly appropriate for targeted HIV screening, since more than 40% of the clients had not previously been tested for HIV even though they engaged in sex-related HIV risk behaviour.

Geographical effects on the accuracy of textile trade data:an international approach for 1913

Foreign trade statistics are the main data source to the study of international trade.However its accuracy has been under suspicion since Morgernstern published hisfamous work in 1963. Federico and Tena (1991) have resumed the question arguing thatthey can be useful in an adequate level of aggregation. But the geographical assignmentproblem remains unsolved. This article focuses on the spatial variable through theanalysis of the reliability of textile international data for 1913. A geographical biasarises between export and import series, but because of its quantitative importance it canbe negligible in an international scale.

The concept of instability: a French perspective on the concept of ADHD.

Historical references to the emergence of the current concept of ADHD typically cite descriptions from medical textbooks by Weikard (1775) and Crichton (An inquiry into the nature and origin of mental derangement: Comprehending a concise system of the physiology and pathology of the human mind and a history of the passion and their affects. Cardell Jr and Davies, Londres, 1798) on attention disorders, poems of Hoffman on hyperactive and impulsive behaviors (Der Struwwelpeter. Frankfurt am Main, Literarische Anstalt, 1843), as well as the work of Still (Lancet 1:1008-1012, 1077-1082, 1163-1168, 1902a, Lancet 159(4102):1008-1013, 1902b, Lancet 159(4103):1077-1082, 1902c, Lancet 159(4104):1163-1168, 1902d) on impulsive behaviors and defective moral regulation of behavior. The notion of "instability" developed by French physicians between 1887 and 1910 is rarely mentioned and often ignored. Writings from this period show that in France, the emergence of the concept of ADHD according to modern terminology comes from the notion of "mental instability" introduced in the 1890s under the leadership of Désiré-Magloire Bourneville at the Hospital Bicêtre in Paris, based on his observations of children and adolescents who had been labeled "abnormal" and placed in medical and educational institutions. In the early twentieth century, elaborating on the observations of Bourneville, Jean Phillipe and Georges Paul-Boncour showed the presence of a subgroup of "unstable" children who suffered from a disease entity in its own right within the population of "abnormal" schoolchildren (the terminology of the time). This new pathological entity included symptoms of hyperactivity, impulsivity and inattention, corresponding to today's classic triad of ADHD symptoms. While noting the lack of behavioral inhibition, clinical descriptions of Bourneville, Philip and Paul-Boncour also considered the notion of "moral disorder" which at that time played an important role in psychopathology. This resulted in some degree of confusion between impulsive symptoms and major behavioral disturbances often associated with ADHD.

On the origins of electoral systems and political parties. The role of elections in multi-member districts

The old, understudied electoral system composed of multi-member districts, open ballot and plurality rule is presented as the most remote scene of the origin of both political parties and new electoral systems. A survey of the uses of this set of electoral rules in different parts of the world during remote and recent periods shows its wide spread. A model of voting by this electoral system demonstrates that, while it can produce varied and pluralistic representation, it also provides incentives to form factional or partisan candidacies. Famous negative reactions to the emergence of factions and political parties during the 18th and 19th centuries are reinterpreted in this context. Many electoral rules and procedures invented since the second half of the 19th century, including the Australian ballot, single-member districts, limited and cumulative ballots, and proportional representation rules, derived from the search to reduce the effects of the originating multi-member district system in favor of a single party sweep. The general relations between political parties and electoral systems are restated to account for the foundational stage here discussed.

Archaeology on the Road, July 2008

Team Archaeology is excited to be riding with you this year! We hope to make our participation an annual opportunity to share the story of Iowa’s amazing past. As you ride across the state you will be passing by the locations of hundreds of known archaeological sites and an as yet unknown number of new discoveries waiting to be made. These archaeological sites, and the artifacts they contain, tell the history of the first people to travel this landscape and the stories of each generation that has contributed to what we know of ourselves today. As you travel through our beautiful state, you too are now a part of that story, making history for the future to learn and wonder about! The Office of the State Archaeologist serves a unique dual role in Iowa as both a designated research unit of The University of Iowa and as a state agency. The larger mission of the OSA is to develop, disseminate, and preserve knowledge of Iowa’s human past through Midwestern and Plains archaeological research, scientific discovery, public stewardship, service, and education. It is our goal to provide all Iowans the opportunity to learn about their past. I see this as an investment in the preservation of a nonrenewable resource—the archaeological record of Iowa. Look for the Team Archeology members as you ride and be sure to ask them about Iowa archeology. Please help yourself to free materials about our shared past from our information tables at each overnight town and get one of the free Iowa Archeology wrist bands. There will also be free public talks by local archaeologists each afternoon, as well as flintknapping and other demonstrations of archaeological interest, so keep this booklet as your guide to the week’s activities. Most of all, ride smart, be safe, and when you get home tell your friends and neighbors about Iowa archaeology!

On the accuracy of Latin American trade statistics: A nonparametric test for 1925

This paper proposes a nonparametric test in order to establish the level of accuracy of theforeign trade statistics of 17 Latin American countries when contrasted with the trade statistics of the main partners in 1925. The Wilcoxon Matched-Pairs Ranks test is used to determine whether the differences between the data registered by exporters and importers are meaningful, and if so, whether the differences are systematic in any direction. The paper tests for the reliability of the data registered for two homogeneous products, petroleum and coal, both in volume and value. The conclusion of the several exercises performed is that we cannot accept the existence of statistically significant differences between the data provided by the exporters and the registered by the importing countries in most cases. The qualitative historiography of Latin American describes its foreign trade statistics as mostly unusable. Our quantitative results contest this view.