Giant cell arteritis with spontaneous remission.

BACKGROUND: Clinical manifestations of giant cell arteritis (GCA) are variable. Whether signs and symptoms present in an explosive fashion or insidiously, once manifest the course is usually progressive unless treatment is initiated. METHODS: A retrospective review of patients with GCA seen in an outpatient neuro-ophthalmology clinic. RESULTS: We report four patients with biopsy-proven GCA who experienced spontaneous remission. Clinical manifestations consisted of headache and diplopia in two patients, constitutional symptoms in one patient and facial pain in another. CONCLUSIONS: Clinicians should be aware of this aspect of the disease in order to avoid a delay in diagnosis and treatment.

Étude de la fonction de GLUT8 sur un modèle de souris "knock-out"

Résumé GLUT8 est la première des nouvelles isoformes des GLUT récemment identifiés. Il est fortement exprimé dans les testicules et plus faiblement dans les blastocystes, le cerveau, particulièrement au niveau de l'hippocampe, et le coeur. En conditions basales, il est retenu dans un compartiment intracellulaire. Si on l'exprime en surface cellulaire, par la mutation du motif d'internalisation dileucine, il transporte le glucose avec une bonne affinité. Dans le but d'étudier sa fonction au niveau de l'organisme, nous avons créé un modèle de knock out conditionnel, en entourant le dernier exon du gène de GLUT8 par deux sites loxP. En croisant nos souris avec une souche de souris transgénique exprimant la cre-recombinase dans les cellules de la lignée germinale, nous avons généré un modèle de souris portant la délétion totale de GLUT8 de manière constitutionnelle. Les statistiques effectuées sur les premières naissances indiquent qu'une partie des souris knock out ne survit pas, suggérant un rôle de GLUT8 au niveau du développement embryonnaire. Les souris qui ont survécu ne présentent toutefois pas d'anomalies durant la croissance et sont fertiles. Elles ont des taux de glucose et d'insuline sanguins normaux. Au niveau cérébral, la structure de l'hippocampe n'est pas modifiée par la suppression de GLUT8, cependant, les souris GLUT8-/- présentent une prolifération cellulaire augmentée dans le gyrus denté. Cette augmentation de division cellulaire pourrait être la réponse adaptée à une éventuelle augmentation de la mort cellulaire au niveau de l'hippocampe. Elles ne semblent toutefois pas présenter de défauts cognitifs majeurs dans le bassin de Morris en conditions normales. Toutefois, en conditions de jeûne, elles tendent à une meilleure mémorisation à court terme. Les études morphologiques et histologiques au niveau cardiaque n'ont pas révélé de d'hypertrophie au niveau ventriculaire. La stimulation de la contraction à l'isoprotérénol n'a pas mis en évidence de défaut d'adaptation des coeurs GLUT8-/-. Cependant l'analyse fonctionnelle par électrocardiogramme, en conditions basales, a montré une augmentation de la durée de l'onde P, suggérant un défaut dans la dépolarisation des oreillettes. Nos résultats indiquent que GLUT8 ne joue pas un rôle prédominant dans la survie et la fonction basale des souris. Il pourrait jouer un rôle plus important dans des situations stressantes pour l'organisme, comme l'hypoglycémie ou les conditions d'ischémie qui induiraient son expression à la membrane plasmique et stimuleraient le captage du glucose. Abstract GLUT8 was the first of the recently identified isoform of the GLUT family proteins. It is strongly expressed in the testis. It is also found at a lower level in the blastocyst, in heart and in the brain. Under basal conditions, it is retained in the intracellular compartment, but when the internalization motif dileucine is mutated, GLUT8 translocates to the plasma membrane and transports glucose with a relatively high affinity. To study its function in vivo, we created a conditional knock out mouse model. To do so, we targeted the last exon of the GLUT8 gene with two loxP sites. We then crossed these mice with a transgenic model expressing the cre-recombinase in the gem' line to generate a constitutional total knock out mouse. The statistics made on the first breedings showed that some of the knock out mice do not survive, suggesting a role of GLUT8 in the embryonic development. Conversely mice who survive do not show developmental defects and they are fertile with normal glucose and insulin blood levels. In the brain, the general structure of the hippocampus is not modified by the deletion of GLUT8. However, GLUT8-/- mice show an increase in the cell proliferation in the dentate gyms. This cell proliferation could be due to an increase in the cell death in the hippocampus. When tested in the morris water maze, these mice do not show any cognitive defects in the basal conditions, but they have a tendency to learn better in fasted conditions. The morphological and histological studies made at the heart level did not show any cardiac hypertrophy in the ventricles. The stimulation with isoproterenol did not show any adaptation defects in the GLUT8-/- hearts. However, the functional analysis made in basal conditions with the electrocardiogram showed an increase in the P wave length, suggesting a defect in the atrial depolarization in the knock out mice. Overall, our results show that GLUT8 does not play an important role in the basal general functions in the mice, but might play a more important role during whole organism stress. Hypoglycaemia or ischemia, for example could stimulate the GLUT8 translocation to the plasma membrane to increase specifically glucose uptake. Résumé tout public Les différentes cellules de l'organisme possèdent des propriétés particulières, qui leur permettent de maintenir les fonctions de l'organe auquel elles appartiennent. La membrane plasmique qui les délimite sélectionne les substances qui vont pénétrer à l'intérieur de la cellule et permet ainsi de maintenir un environnement interne constant. Le glucose est une source d'énergie importante pour la cellule et doit pouvoir pénétrer à l'intérieur de la cellule. Il utilise pour cela des protéines de transport qui le feront passer de part et d'autre de la membrane. Les protéines de la famille des GLUT (pour GLUcose Transporter) possèdent cette capacité. GLUT8 est un membre de la famille des GLUT identifié récemment. Il possède la capacité de transporter le glucose quand il se présente à la surface de la cellule. Il est principalement exprimé dans les testicules, dans le coeur et le cerveau et durant le développement embryonnaire. Son rôle n'est toutefois pas encore défini. Ce travail consiste à étudier la fonction de GLUT8 au niveau de l'organisme entier. Nous avons créé un modèle de souris dans lesquelles l'expression de GLUT8 a été supprimée pour mettre en évidence son importance dans le maintien de l'intégrité des fonctions du corps. Les observations effectuées sur les souris qui n'expriment plus GLUT8 nous indiquent que leurs cellules prolifèrent plus vite au niveau de l'hippocampe. L'hippocampe est une structure située dans le cerveau qui est impliquée dans les phénomènes d'apprentissage. Les souris qui ont été testées dans des tâches d'apprentissage n'ont malgré cela pas montré une amélioration de la mémorisation. Dans le coeur, la suppression de GLUT8 semble présenter un défaut quand on mesure l'activité électrique du coeur par électrocardiogramme. Toutefois, ils fonctionnent normalement et ne présentent pas de défauts morphologiques en conditions normales. Les expériences effectuées sur les modèles de souris indiquent que GLUT8 ne jouerait pas un rôle prédominant dans le fonctionnement normal du corps. Il pourrait exercer sa fonction dans des situations plus particulières comme l'hypoglycémie, où il permettrait une meilleure capacité à transporter le glucose dans les cellules.

The legal and ethical framework governing Body Donation in Europe - A review of current practice and recommendations for good practice

Discussions at the inaugural meeting of a Trans-European Pedagogic Research Group for Anatomical Sciences highlighted the fact that there exist considerable variations in the legal and ethical frameworks throughout Europe concerning body bequests for anatomical examination. Such differences appear to reflect cultural and religious variations as well as different legal and constitutional frameworks. For example, there are different views concerning the "ownership" of cadavers and concerning the need (perceived by different societies and national politicians) for legislation specifically related to anatomical dissection. Furthermore, there are different views concerning the acceptability of using unclaimed bodies that have not given informed consent. Given that in Europe there have been a series of controversial anatomical exhibitions and also a public (televised) dissection/autopsy, and given that the commercial sale or transport of anatomical material across national boundaries is strongly debated, it would seem appropriate to "harmonise" the situation (at least in the European Union). This paper summarises the legal situation in a variety of European countries and suggests examples of good practice. In particular, it recommends that all countries should adopt clear legal frameworks to regulate the acceptance of donations for medical education and research. It stresses the need for informed consent, with donors being given clear information upon which to base their decision, intentions to bequest being made by the donor before death and encourages donors to discuss their wishes to bequeath with relatives prior to death. Departments are encouraged, where they feel it appropriate, to hold Services of Thanksgiving and Commemoration for those who have donated their bodies. Finally, there needs to be legislation to regulate transport of bodies or body parts across national borders and a discouragement of any moves towards commercialisation in relation to bequests.

Revealing the dark side of traditional democracies in plurinational societies. The case of Catalonia and the Spanish “Estado de las Autonomías”

In this article, I firstly offer a synthesis of a brief set of analytical elements of the theory of democracy and federalism established in the recent debate which identify a number of flaws in the normative and institutional bases of plurinational democracies. It is necessary to overcome these flaws in order to achieve a true political and constitutional recognition and accommodation of the national pluralism of this kind of liberal democracies (section 1). Secondly, we will focus on the Spanish case of the “Estado de las Autonomías” taking into account the recent reform of the Catalan constitutional law (Estatut d’autonomia 2006) (section 2). A final section makes a number of concluding remarks relating the previously highlighted elements of the theory of democracy and federalism with the analysis of the Catalan case (section 3).

Recognition and political accommodation: from regionalism to secessionism. The Catalan case

Having lived through a bloody civil war in the 1930s followed by four decades of General Franco’s dictatorship, the Spanish state carried out a transition to a democratic system at the end of the 1970s. The 1978 Constitution was the legal outcome of this transition process. Among other things, it established a territorial model – the so-called “Estado de las Autonomías” (State of Autonomous Communities) – which was designed to satisfy the historical demands for recognition and self-government of, above all, the citizens and institutions of Catalonia and the Basque Country .In recent years support for independence has increased in Catalonia. Different indicators show that pro-independence demands are endorsed by a majority of its citizens, as well as by most of the political parties and organizations that represent its civil society. This is a new phenomenon. Those in favour of independence had been in the minority throughout the 20th century. Nowadays, however, demands of a pro-autonomy and pro-federalist nature, which until recently had been dominant, have gradually lost public support in favour of demands for self-determination and secession. This paper analyses the massive increase in support for secession in Catalonia during the early years of the 21st century. After describing the different theories of secession in plurinational liberal democracies (section 1), we analyse Catalonia’s political evolution over the past decade focusing on the shortcomings with regard to constitutional recognition and accommodation displayed by the Spanish political system. The latter have been exacerbated by the reform process of Catalonia’s Statute of Autonomy (2006) and the subsequent judgement of Spain’s Constitutional Court regarding the aforementioned Statute (2010) (section 2). Finally, we present our conclusions by linking the Catalan case with theories of secession applied to plurinational contexts

Federalism and democracy. The case of minority nations: a federalist deficit

In this chapter, after pointing out the different logics that lie behind the familiar ideas of democracy and federalism, I have dealt with the case of plurinational federal democracies. Having put forward a double criterion of an empirical nature with which to differentiate between the existence of minority nations within plurinational democracies (section 2), I suggest three theoretical criteria for the political accommodation of these democracies. In the following section, I show the agonistic nature of the normative discussion of the political accommodation of this kind of democracies, which bring monist and pluralist versions of the demos of the polity into conflict (section 3.1), as well as a number of conclusions which are the result of a comparative study of 19 federal and regional democracies using four analytical axes: the uninational/plurinational axis; the unitarianism-federalism axis; the centralisation-decentralisation axis; and the symmetry-asymmetry axis (section 3.2). This analysis reveals shortcomings in the constitutional recognition of national pluralism in federal and regional cases with a large number of federated units/regions with political autonomy; a lower degree of constitutional federalism and a greater asymmetry in the federated entities or regions of plurinational democracies. It also reveals difficulties to establish clear formulas in these democracies in order to encourage a “federalism of trust” based on the participation and protection of national minorities in the shared government of plurinational federations/regional states. Actually, there is a federal deficit in this kind polities according to normative liberal-democratic patterns and to what comparative analysis show. Finally, this chapter advocates the need for a greater normative and institutional refinement in plurinational federal democracies. In order to achieve this, it is necessary to introduce a deeper form of “ethical” pluralism -which displays normative agonistic trends, as well as a more “confederal/asymmetrical” perspective, congruent with the national pluralism of these kind of polities.

Migrating concepts: Immigrant integration and the regulation of religious dress in France and Canada

Religion in general, and Islam in particular, has become one of the main focal points of policy-making and constitutional politics in many Western liberal states. This article proposes to examine the legal and political dynamics behind new regulations targeting individual religious practices of Muslims. Although one could presuppose that church-state relations or the understanding of secularism is the main factor accounting for either accommodation or prohibition of Muslim religious practices, I make the case that the policy frame used to conceptualize the integration of immigrants in each national context is a more significant influence on how a liberal state approaches the legal regulation of individual practices such as veiling. However, this influence must be assessed carefully since it may have different effects on the different institutional actors in charge of regulating religion, such as the Courts and the legislature. To assess these hypotheses I compare two countries, France and Canada, which are solid examples of two contrasting national policy frames for the integration of immigrants.

Mutations in CEP57 cause mosaic variegated aneuploidy syndrome.

Using exome sequencing and a variant prioritization strategy that focuses on loss-of-function variants, we identified biallelic, loss-of-function CEP57 mutations as a cause of constitutional mosaic aneuploidies. CEP57 is a centrosomal protein and is involved in nucleating and stabilizing microtubules. Our findings indicate that these and/or additional functions of CEP57 are crucial for maintaining correct chromosomal number during cell division.

Continuity of Government Planning Interim Study Committee, March 2007

The Legislative Council established the Continuity of Government Planning Interim Study Committee in 2006 and authorized the Committee to meet during the 2006 Legislative Interim. The Committee was given the following charge: Examine issues relating to the continued functioning of state government following a disaster, including gubernatorial succession, replacement of constitutional officers and department heads, legislative elections to fill vacancies, and continued funding of state government if the General Assembly is unable to meet and pass a budget.

Iowa Budget Report, Building on our Progress: Protecting our Priorities, 2009

*********** Some files are large and will take time to load. *********** Seven Files: 1)Report Cover, 2)Table of Contents, 3)Statewide Financial Summaries, 4)Department Budgets, 5)Capitol Projects, 6)Associated Financial Documents, 7)Budget Report. To Members of the 82nd General Assembly, As we begin the second year of our Administration, we are pleased to submit the Fiscal Year 2009 budget for the State of Iowa pursuant to Iowa Code Section 8.21 and our constitutional authority. This budget recognizes the progress that we began last year with improvements in education, economic development, energy independence, and health care; provides funding for new policy initiatives in these areas; and is based on fiscally sound budget practices. Building on last year’s accomplishments, our Fiscal Year 2009 General Fund budget proposes an additional $75 million for increasing teachers’ salaries as part of our goal to move Iowa closer to the national average. We lay the foundation for student achievement by recommending $32.1 million for pre-school education, and we also propose $177.5 million in total for community colleges and $726.2 million in total for Regents universities. To make our State more energy independent, our General Fund budget appropriates the second-year funding of $25 million for the new Iowa Power Fund. The newly established Office of Energy Independence will soon start making awards from the Power Fund. Apart from the budget, we will be making several proposals to implement the new State energy plan. We have pledged to expand the number of Iowans who have health-care coverage. As a result, we are recommending additional funding for enrollment growth in the State Children Health Insurance Program (SCHIP). These additional funds will help the State provide coverage for another 25 percent of children who are eligible but not yet enrolled in hawk-i and the Iowa Medicaid Program. To protect the safety of Iowans, we are recommending issuance of revenue bonds for approximately $260 million in net proceeds to build a new state penitentiary in Ft. Madison, renovate and expand the Women’s Correctional Institution at Mitchellville, upgrade kitchen facilities at the Rockwell City and Mt. Pleasant Correctional Institutions, and expand Community-Based Correctional Facilities in Ottumwa, Sioux City, Waterloo, and Des Moines. Additionally, we are including funding for developing a prototype program for providing parolees and low-risk offenders with mental health and drug abuse treatment and educational services to help them make a crime-free re-entry into our communities. As part of this Capitals Budget, we also propose using $20 million for the State’s matching share for building new facilities at the Iowa Veterans Home. Iowa Budget Report iv Fiscal Year 2009 Importantly, our budget continues to fully fund our State’s Reserve Funds to help buffer Iowa from any future economic downturn. We recommend reimbursing $78.2 million to the Property Tax Credit Fund as part of our multi-year proposal to correct bad budgeting practices and eventually restore $160.0 million to this Fund. To provide more transparency, we are transferring operational expenditures in the Rebuild Iowa Infrastructure Fund to the General Fund and expenditures from the Endowment for Healthy Iowans and Healthy Iowans Tobacco Trust Funds to the General Fund. We believe that Iowa has charted a new course of becoming energy independent, providing quality pre-school education, recognizing the importance of our teachers, and providing greater health coverage for children. Our Fiscal Year 2009 budget and policy priorities reflect our continuing faith in Iowa’s ability to be the best state in the nation. We look forward to working with you in a bi-partisan and all-inclusive manner to build on our progress and protect our priorities. Sincerely, Chester J. Culver Governor Patty Judge Lt. Governor

Executive Order Number Ten, December 22, 2008

This Executive Order aids the Governor to meet his Constitutional obligation to balance the state budget, announcing that he would order a 1.5 percent across-the-board reduction in state expenditures for the current fiscal year.

O Sistema Semi-Presidencialista Cabo-verdiano: A Relação entre os Poderes Executivo e Legislativo

O artigo procura analisar a relação que se estabelece entre o poder executivo e legislativo no sistema de governo cabo-verdiano, onde Investigadores buscam compreendê-lo, tendo em conta a sua configuração prática, teórica e constitucional. Há que realçar a proeminência do debate e dos estudos realizados no sentido de compreender como é que a academia científica procura debelar esta problemática. Duas questões são pertinentes neste debate: a primeira refere-se à configuração teórico-constitucional do sistema de governo cabo-verdiano e a outra à prática política e legislativa.

The semi-presidential system of Cape Verde: the relationship between the executive and the legislative powers = O sistema semi-presidencialista caboverdiano: a relação entre os poderes executivo e legislativo

e article analyses the relationship established between the executive and legislative powers in the Cape Verdean government system where researchers seek to understand it, taking into account their theoretical and constitutional setting practice. It should be noted the prominence of the debate and studies undertaken to understand how the scienti c academy seeks to eradicate this problem. Two issues are relevant in this debate: the rst reporting to the theoretical and constitutional con guration of Cape Verdean government system and the other to its policy and legislative practice. Keywords: Cape Verde. Semi-presidential System. Systems of Government. Legislative and Executive Powers.

5-Azacytidine to Treat Acute Myeloid Leukemia In Elderly or Frail Patients: A Phase II Study (SAKK 30/07).

Background: Acute Myeloid Leukemia (AML) in the elderly is notoriously difficult to treat and has a low remission rate with very few long term survivors when using standard treatment approaches. Azacytidine, a hypomethylating agent, has been shown to induce remission and prolong survival in patients with myelodysplastic syndromes; studying this approach to patients with AML is therefore warranted. We present results of an ongoing phase II trial treating elderly or frail AML patients with Azacytidine. Methods: AML elderly or frail patients, and therefore unfit for an intensive chemotherapy regimens, with a WHO performance status 3 were considered for this trial. Trial therapy consisted of 100mg/m2 of Azacytidine injected subcutaneously on 5 consecutive days every 28 days up to 6 cycles, stopping at 6 months if no hematological improvement achieved, or earlier in the case of progression or complications. Treatment was continued beyond 6 months in responding patients. Trial therapy was considered uninteresting if the response rate (CR + PR) within 6 months of therapy initiation was 15% or less and promising if 34% or more. Using the exact single-stage phase II design by A'Hern with a 5% significance level and 90% power, 43 patients were required: If 10 or fewer achieved a response within 6 months the trial therapy should not be considered for further investigation in its current format for this indication and patient population. Results: Between September 2008 and January 2010, 45 evaluable patients across 10 Swiss centers were accrued with a median follow-up of 7 months (range: 0 - 13). 27 (60%) were male, median age was 74 (range: 55 - 86) years and 35 (78.8%) had performance status 0-1. Patients had been excluded from more intensive chemotherapy regimens because of age (n = 37) or due to comorbidities or patient refusal (n=8). Five patients had therapy related AML. Patients received a median of 3 (range: 1 - 10) cycles. Treatment was stopped for not achieving a response by the 6th cycle in 2 patients and earlier in 26 patients (for disease progression in 5, toxicity in 3, patient refusal in 2, recurrent infections in 1, and death in 8). Seventeen patients remain on therapy. The median time spent in the hospital was 12 days (1 - 30) in 24/38 patients hospitalized during the first treatment cycle and 13 days (2 - 28) in 15/31 patients hospitalized during subsequent cycles. Adverse events of grade III or higher most frequently reported were constitutional or hematologic, i.e. fatigue in 5, febrile neutropenia in 8, infections in 6, dyspnea in 6, anemia in 3, neutropenia in 12 and thrombocytopenia in 10, hemorrhage in 2 and retinal detachment in 5. Based on available data on 38 patients, CR/CRi or hematologic improvement or stable disease within 6 months of trial registration was observed in a proportion of patients. Final and mature data, determining whether the predefined proportion of responding patients has been reached or not, will be presented at the conference. Up to now there were a total of 26 deaths. Median overall survival time was 5.7 months (95% CI: 3.1, 8.7). Conclusions: The current results of this slightly modified Azacytidine schedule demonstrate a feasible new therapy option for elderly or frail AML patients in an outpatient setting with moderate, mainly hematologic toxicity.