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The Forkhead box G1 (FoxG1) is a transcription factor essential for the forebrain development and involved in pathogenesis of Rett syndrome. Notwithstanding the importance of this protein, little is known about the modalities by which it exerts its cellular functions. In this thesis I investigated, in cell culture and in animal model, the molecular mechanisms of Foxg1 action and the pathophysiological consequences of Foxg1 haploinsufficiency. Using fluorescence recovery after photobleaching strategy, I investigated the chromatin binding dynamics of Foxg1 in its wild-type form or carrying some Rett syndrome-causing mutations. The experiments show that GFP-Foxg1 mobile molecules have a chromatin affinity that decreases in truncated mutants with the extension of the protein deletion. Conversely, the immobile fraction does not decrease gradually with the extension of protein deletion but is significantly higher for a truncation associated with a severe phenotype, suggesting a possible dominant negative function of some RTT mutants. As already present in literature, GFP-Foxg1 localizes almost exclusively in the nucleus. However, no one reported data on Foxg1-GFP C-terminal fusion protein. Surprisingly, Foxg1 wt-GFP, in addition to the preserved nuclear localization, shows a clear mitochondrial localization. Further investigation led me to discover that Foxg1 undergoes a proteolytic cleavage and the resulting C-terminal peptide localizes to mitochondria, as evidenced by CFP-Foxg1 wt-YFP fusion protein as well as by other biochemical and immunohistochemical assays. Tripan Blue and proteinase K protection experiments in living cells show that nearly 80% of the protein reside in the mitochondrial matrix. Considering that Foxg1 does not have a classical N terminal mitochondrial targeting signal, I looked for Foxg1 amino acids able to drive a fused fluorescent tag into mitochondria and identified amino acids 277-302 as critical. A pull down experiment showed that a "mitochondrial" Foxg1 peptide interacts with some proteins involved in mitochondrial trafficking and function such as voltage dependent anion channel 1 and 2. Functionally, a C-terminal "mitochondrial" peptide of Foxg1 (aa 272-481) is able to enhance ATP production and mitochondrial membrane potential. Full length Foxg1 strikingly enhances mitochondrial potential and promotes cellular proliferation and mitochondrial fission; on the contrary, "mitochondrial" Foxg1 promotes mitochondrial fusion and an initial stage of cellular differentiation. In an animal model, I investigated the functional result of Foxg1 haploinsufficiency in mouse visual system. We chose visual system since it is known that Foxg1 is expressed in the developing retina and chiasm and the knockout mouse embryos show defects in retinal ganglion cells axonal navigation. It is also known that Foxg1 haploinsufficiency in mice results in subtle cortical defects. My data show that Foxg1+/Cre heterozygous mice have a profound impairment in visual acuity, despite a preserved retinal organization. Defects in visual cortical circuitry suggest that acuity loss may be due to altered cortical mechanisms. Taken together, these results suggest the following hypothesis: Foxg1 is a nuclear and mitochondrial protein that upon its internal processing localizes in the mitochondrial compartment and becomes a key coordination part of the machinery that brings about cell differentiation, replication and bioenergetics.

years have raised increasing interest. Many applications of astronomical observation techniques, as coronography and interferometry get great benefit when moved in space and the employment of diluted systems represents a milestone to step-over in astronomical research. In this work, we present the Optical Position Sensors Emitter (OPSE) metrological sub-system on-board of the PROBA3. PROBA3 is an ESA technology mission that will test in-orbit many metrology techniques for the maintenance of a Formation Flying with two satellites, in this case an occulter and a main satellite housing a coronagraph named ASPIICS, kept at an average inter-distance of 144m. The scientific task is the observation of the Sun’s Corona at high spatial and temporal resolution down to 1.08R⊙. The OPSE will monitor the relative position of the two satellites and consists of 3 emitters positioned on the rear surface of the occulter, that will be observed by the coronagraph itself. A Centre of Gravity (CoG) algorithm is used to monitor the emitter’s PSF at the focal plane of the Coronagraph retrieving the Occulter position with respect to the main spacecraft. The 3σ location target accuracy is 300μm for lateral movement and 21cm for longitudinal movements. A description of the characterization tests on the OPSE LED sources, and of the design for a laboratory set-up for on ground testing is given with a preliminary assessment of the performances expected from the OPSE images centroiding algorithm.

Here we report the detection of a 626 s periodic modulation from the X-ray source 2XMM J174016.0-290337 located in the direction of the Galactic center. We present temporal and spectral analyses of archival XMM-Newton data and photometry of archived near-infrared data in order to investigate the nature of this source. We find that the X-ray light curve shows a strong modulation at 626 +/- 2 s with a confidence level > 99.9% and a pulsed fraction of 54%. Spectral fitting demonstrates that the spectrum is consistent with an absorbed power law. No significant spectral variability was observed over the 626 s period. We have investigated the possibility that the 626 s period is orbital in nature (either that of an ultra-compact X-ray binary or an AM CVn) or related to the spin of a compact object (either an accretion powered pulsar or an intermediate polar). The X-ray properties of the source and the photometry of the candidate near-infrared counterparts are consistent with an accreting neutron star X-ray binary on the near-side of the Galactic bulge, where the 626 s period is most likely indicative of the pulsar spin period. However, we cannot rule out an ultra-compact X-ray binary or an intermediate polar with the data at hand. In the former case, if the 626 s modulation is the orbital period of an X-ray binary, it would be the shortest period system known. In the latter case, the modulation would be the spin period of a magnetic white dwarf. However, we find no evidence for absorption dips over the 626 s period, a low temperature black body spectral component, or Fe Kalpha emission lines. These features are commonly observed in intermediate polars, making 2XMM J174016.0-290337 a rather unusual member of this class if confirmed. We instead suggest that 2XMM J174016.0-290337 could be a new addition to the emerging class of symbiotic X-ray binaries., 11 pages, 10 figures, submitted to A&A on 18th January 2010, accepted for publication 20th August 2010

Colorectal cancer (CRC) represents one of the most relevant causes of morbidity and mortality in Western societies. CRC screening is actually based on faecal occult blood testing, and optical colonoscopy still remains the gold standard screening test for cancer detection. However, computed tomography colonography (CT colonography) constitutes a reliable, minimally-invasive method to rapidly and effectively evaluate the entire colon for clinically relevant lesions. Furthermore, even if the benefits of its employment in CRC mass screening have not fully established yet, CT colonography may represent a reasonable alternative screening test in patients who cannot undergo or refuse colonoscopy. Therefore, the purpose of our review is to illustrate the most updated recommendations on methodology and the current clinical indications of CT colonography, according to the data of the existing relevant literature.

International audience; BACKGROUND: EHT0202 (etazolate hydrochloride) is a new compound exhibiting both potential disease-modifying and symptomatic treatment properties in Alzheimer's Disease increasing alpha-secretase activity and sAPP alpha secretion, as well as acting as a GABA-A receptor modulator and as a PDE-4 inhibitor. METHODS: This pilot, randomized, double-blind, placebo-controlled, parallel group, multicentre, Phase IIA study was conducted in 159 randomized patients suffering from mild to moderate Alzheimer's Disease. EHT0202 (40 or 80 mg bid) or placebo was administered as adjunctive therapy to one acetylcholinesterase inhibitor over a 3-month period. This study was designed to assess the clinical safety and tolerability of EHT0202 as a primary objective, with secondary endpoints (cognitive function, daily living activities, behaviour, caregiver burden and global functioning) included to explore clinical efficacy of EHT0202 versus placebo. RESULTS: EHT0202 was shown to be safe and generally well tolerated. Dose-dependent numbers of early withdrawal and central nervous system related adverse events were observed. As expected, since the study was not powered and not designed to show drug efficacy, and except for ratings on the ADCS-ADL scale, no significant differences were seen between treatment groups. CONCLUSIONS: These first encouraging safety results do support further development of EHT0202 in order to assess its clinical efficacy and to confirm its tolerability in a larger cohort of Alzheimer patients and for a longer period.

We use more than a century of Argentine and Mexican data to estimate the structural parameters of a small-open-economy real-business-cycle model driven by nonstationary productivity shocks. We find that the RBC model does a poor job of explaining business cycles in emerging countries. We then estimate an augmented model that incorporates shocks to the country premium and financial frictions. We find that the estimated financial-friction model provides a remarkably good account of business cycles in emerging markets and, importantly, assigns a negligible role to nonstationary productivity shocks. (JEL E13, E32, E44, F43, O11, O16)

Cette communication vise a elargir le domaine conceptuel des consultations memoire. Cible : Elle s’adresse a des psychiatres, geriatres, psychologues et a tout medecins et soignants concernes par la problematique de la plainte cognitive. Objectif general : definir un algorithme de diagnostic et de soin selon les tranches d’âges de patients amenes a consulter pour des troubles cognitifs Objectifs secondaires : connaitre les principaux diagnostics selon l’âge et les consequences pour la prise en charge Si les consultations memoire sont classiquement rattachees en France a la filiere geriatrique, l’experience de notre consultation de province, assez isolee sur son territoire montre que l’âge peut s’etaler de 17 a 101 ans ! La moyenne etant neanmoins de 74,9 ans. L’analyse de notre file active s’est faite sur les bases de la BNA (Banque Nationale Alzheimer) en 2017. La file active est de 664 patients differents sur 1400 venues avec 389 nouveaux patients. La motivation pour consulter en consultation memoire apparait fortement correlee a l’âge. Si l’on considere les tranches d’âge de 10 ans en 10 ans l’on constate de grande variabilite de diagnostic. Chez les plus jeunes la patho logie psychiatrique et les traumatismes crâniens sont au premier plan. Avant 65 ans, ce sont 30 % des patients qui souffrent de pathologies psychiatriques (bipolarite, depression, anxiete, schizophrenie) et de l’impact cognitif negatif des psychotropes. Plus on avance vers le milieu de vie, plus les pathologies vasculaires sont en cause (sequelle d’AVC) ainsi que des encephalopathies : auto immunes, toxiques, carentielles et rarement neurodegeneratives (SEP, DFT, Parkinson, DCL). La plainte cognitive croit jusqu’a 70 ans (26 %) et oblige a interroger les dimensions psychologiques sous-jacentes. Apres 75 ans, les maladies d’Alzheimer et apparentees passent au premier plan et avec elles les demandes outre de diagnostic mais aussi de gestion de troubles de comportement. Cette difference nous oblige a revoir notre demarche diagnostique et bien sur notre plan de soin. Ainsi, la demande en consultation memoire n’est pas que geriatrique, elle transcende les âges ce qui n’est pas sans incidence en termes de politique de sante. Les dynamiques psychologiques des patients et des aidants different egalement selon la population cible. Ce constat oblige a developper une attitude ouverte et collegiale, a s’entourer d’une solide expertise psychiatrique, a trouver des partenaires aptes a offrir une offre sociale, psychotherapeutique et reeducative adaptee, de meme que des referents differents selon l’âge en medecine interne, cardiologie puis en geriatrie generaliste. Toutefois le handicap cognitif apparait transversal quelque soient les generations.

Composites of polystyrene (PS) with cellulose microfibres and oat particles, obtained by melt mixing, were examined. The compatibilization of the composites was carried out by addition of maleic anhydride functionalized copolymers (SEBS-g-MA, PS-co-MA) and poly(ethylene glycol) to improve the fibre–matrix interfacial interactions. The plain components and their composites were characterised by FT-IR, DSC, TGA, SEM microscopy and mechanical tests. The properties of the various systems were analysed as a function of both fibre and compatibilizer amount. The compatibilized PS composites showed enhanced fibre dispersion and interfacial adhesion as a consequence of chemical interactions between the anhydride groups on the polymer chains and the hydroxyl groups on the fibres, as demonstrated by FT-IR spectroscopy. DSC analysis pointed out a neat increase of Tg of composites on addition of SEBS-g-MA, as compared to PS-co-MA. The thermal stability of composites was also influenced by the type and amount of fibres, as well as by the structure and concentration of compatibilizer. The effect of the reactive copolymers on the composites properties was accounted for on the basis of the polymer-polymer miscibility and chemical interactions at the matrix/filler interface.

La prise en charge de certains symptomes delirants, psychotiques et comportementaux du sujet âge recourt frequemment aux antipsychotiques. Les donnees de la litterature mettent toutefois en evidence une grande variabilite des pratiques selon les equipes ainsi que de nombreux mesusages dans l’utilisation de cette classe therapeutique. Leur prescription chez les sujets âges a ete recemment remise en cause, laissant ainsi les praticiens demunis face a une symptomatologie souvent complexe et difficile a prendre en charge. En pratique clinique, le recours aux antipsychotiques parait incontournable lorsque l’etat delirant du sujet âge revet des consequences graves pour lui-meme et son entourage: detresse psychologique, handicap fonctionnel, mise en danger. Leur prescription devrait demeurer individualisee et limitee dans le temps, chez les patients ou elle se revele efficace et reevaluee tres regulierement. Afin de guider cette prescription sur des preuves, on ne peut que preconiser des etudes fondees sur une methodologie rigoureuse. Dans tous les cas, on devra privilegier l’emploi des molecules les moins anticholinergiques, reduire au minimum la posologie et fractionner les prises dans la journee afin d’ameliorer la tolerance.

An efficient and modulable total synthesis of discodermolide (DDM), a unique marine anticancer polyketide is described including relat- ed alternative synthetic approaches. Particularly notable is the repeated ap- plication of a crotyltitanation reaction to yield homoallylic (Z)-O-ene-carba- mate alcohols with excellent selectivity. Advantage was taken of this reaction not only for the stereocontrolled build- ing of the syn-anti methyl-hydroxy- methyl triads of DDM, but also for the direct construction of the terminal (Z)- diene. Of particular interest is also the installation of the C13=C14 (Z)-double bond through a highly selective dyo- tropic rearrangement. The preparation of the middle C8-C14 fragment in two sequential stages and its coupling to the C1-C7 moiety was a real challenge and required careful optimization. Sev- eral synthetic routes were explored to allow high and reliable yields. Due to the flexibility and robust character of this approach, it might enable a sys- tematic structural variation of DDM and, therefore, the elaboration and ex- ploration of novel discodermolide structural analogues.

Resume Les aidants familiaux de personnes atteintes de maladie d’Alzheimer vivent une relation d’aide a risque. Ils subissent un repli social, une carence en investissements personnels. Leur fardeau est plus subjectif qu’objectif grandement influence par le regard que l’on pose sur eux et la perception qu’ils ont d’eux-memes. Leurs besoins sont d’appui emotionnel, de formation et de repit. Parmi les differentes interventions psychosociales, les programmes psycho-educatifs etales dans le temps, associes a une intervention sur le patient offrent la plus grande efficacite pour combattre la detresse de l’aidant et retarder la mise en institution du patient. Le programme d’education therapeutique propose comporte 26 seances en deux ans. Il vise a augmenter la confiance en soi de l’aidant, ameliorer ses capacites de coping et l’aider a se preserver en gerant son stress.

Forkhead box g1 (Foxg1) is a nuclear-cytosolic transcription factor essential for the forebrain development and involved in neurodevelopmental and cancer pathologies. Despite the importance of this protein, little is known about the modalities by which it exerts such a large number of cellular functions. Here we show that a fraction of Foxg1 is localized within the mitochondria in cell lines, primary neuronal or glial cell cultures, and in the mouse cortex. Import of Foxg1 in isolated mitochondria appears to be membrane potential-dependent. Amino acids (aa) 277–302 were identified as critical for mitochondrial localization. Overexpression of full-length Foxg1 enhanced mitochondrial membrane potential (ΔΨm) and promoted mitochondrial fission and mitosis. Conversely, overexpression of the C-term Foxg1 (aa 272–481), which is selectively localized in the mitochondrial matrix, enhanced organelle fusion and promoted the early phase of neuronal differentiation. These findings suggest that the different subcellular localizations of Foxg1 control the machinery that brings about cell differentiation, replication, and bioenergetics, possibly linking mitochondrial functions to embryonic development and pathological conditions.

We show that the transition from an economy characterized by idiosyncratic\ud income shocks and incomplete markets a la Aiyagari (1994) to markets where statecontingent\ud assets are available but costly (in order to purchase a contingent asset,\ud households have to pay a xed participation cost) leads to a large increase of wealth\ud inequality. Using a standard calibration our model can match a Gini of 0.93 close\ud to the level of wealth inequality observed in the US. In addition, under this level of\ud participation costs, wealth inequality is particularly sensitive to income inequality.\ud We label this phenomenon as the Inequality Accelerator. We demonstrate how\ud costly access to contingent asset-markets generates these e ects. The key insight\ud stems from the non-monotonic relationship between wealth and desired degree of\ud insurance, in an economy with participation costs. Poor borrowing constrained\ud households remain uninsured, middle-class households are almost perfectly insured,\ud while rich households decide to self-insure by purchasing risk-free assets. This\ud feature of households' risk management has crucial e ects in asset prices, wealth\ud inequality, and social mobility.\ud

In this paper we propose a novel explanation for the increase in households’ leverage during the recent boom in U.S. housing prices. We use the U.S. housing market’s boombust episode that led to the Great Recession as a case study, and we show that biased long-run expectations of both households and, especially, financial intermediaries about future housing prices had a large impact on households’ indebtedness. Specifically, first we show that it is likely that financial intermediaries used forecasting models that ignored the long-run mean reversion of housing prices after a short-run momentum, thus leading to an overestimation of future households’ housing wealth. We frame this finding in the theory of natural expectations, proposed by Fuster et al. (2010), to the housing market. Then, using a tractable model of collateralized credit market populated by households and banks, we find that: (1) mild variations in long-run forecasts of housing prices result in quantitatively considerable differences in the amount of home equity extracted during a housing price boom; (2) the equilibrium levels of debt and interest rate are particularly sensitive to financial intermediaries’ naturalness; (3) home equity extraction data are better matched by models in which agents are fairly natural.

Purpose To evaluate feasibility, diagnostic performance, patient acceptance, and overall examination time of CT colonography (CTC) performed through rectal administration of iodinated contrast material. Materials and methods Six-hundred asymptomatic subjects (male:female = 270:330; mean 63 years) undergoing CTC for colorectal cancer screening on an individual basis were consecutively enrolled in the study. Out of them, 503 patients (group 1) underwent CTC with rectal tagging, of which 55 had a total of 77 colonic lesions. The remaining 97 patients (group 2) were randomly selected to receive CTC with oral tagging of which 15 had a total of 20 colonic lesions. CTC findings were compared with optical colonoscopy, and per-segment image quality was visually assessed using a semi-quantitative score (1 = poor, 2 = adequate, 3 = excellent). In 70/600 patients (11.7%), CTC was performed twice with both types of tagging over a 5-year follow-up cancer screening program. In this subgroup, patient acceptance was rated via phone interview two weeks after CTC using a semi-quantitative scale (1 = poor, 2 = fair, 3 = average, 4 = good, 5 = excellent). Results Mean per-polyp sensitivity, specificity, positive and negative predictive values of CTC with rectal vs oral tagging were 96.1% (CI95% 85.4 ÷ 99.3%) vs 89.4% (CI95% 65.4 ÷ 98.1%), 95.3% (CI95% 90.7 ÷ 97.8%) vs 95.8% (CI95% 87.6 ÷ 98.9%), 86.0% (CI95% 73.6 ÷ 93.3) vs 85.0% (CI95% 61.1 ÷ 96.0%), and 98.8% (CI95% 95.3 ÷ 99.8%) vs 97.2% (CI95% 89.4 ÷ 99.5%), respectively (p > 0.05). Polyp detection rates were not statistically different between groups 1 and 2 (p > 0.05). Overall examination time was significantly shorter with rectal than with oral tagging (18.3 ± 3.5 vs 215.6 ± 10.3 minutes, respectively; p Conclusions Rectal iodine tagging can be an effective alternative to oral tagging for CTC with the advantages of greater patient acceptance and lower overall examination time.

In this paper we examine the impact of bailout policies in small open economies that are subject to financial frictions. We extend standard endogenous default models in two ways. First, we augment the government’s choice set with a bailout option. In addition to the standard choice of defaulting or repaying the debt, a government can also choose to ask for third-party bailout, which comes at a cost of an imposed borrowing limit. Second, we introduce financial frictions and a financial intermediation channel, which tie conditions on the private credit market to the conditions on the sovereign credit market. This link has been very strong in European countries during the recent sovereign crisis. We find that the existence of a bailout option reduces sovereign spreads and, through the described link, private credit rates as well. The implementation of a rescue program reduces output losses and increases welfare, measured in consumption equivalent terms. Moreover, bailout benefits emerge even when a government only has the option of asking for a bailout, but does not take advantage of it.

Purpose Methods and materials Results Conclusion Personal information References, Purpose: The recent guidelines on the clinical indications for CTC, developed by the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), recommendCTC referral for endoscopic...

Clinical History Image Findings Discussion Find Diagnosis Differential Diagnosis, female, 73 years, Clinical History: A 73 years-old female patient came to our attention after few episodes of haematemesis  and acute anterior and posterior chest pain. The patient was affected by a known systemic lupus erythematosus. On first examination the patient was conscious and in ... Final Diagnosis: Fissured Thoracic and Abdominal Aortic Aneurysms

Aims and objectives Methods and materials Results Conclusion Personal information References, Aims and objectives: To assess treatment response in patients with head-and-neck cancer followingintensity modulated radiotherapy (IMRT) by means of perfusion CT (pCT) with an effective axial coverage of 8cm and iterative image...

Aims and objectives Methods and materials Results Conclusion Personal information References, Aims and objectives: To establish the role of virtopsy in the evaluation and recognition of trauma dynamics and causes of death whenever great heights fall lesions are present. In great heights falls we observe usually skull, pelvic bone and burst vertebral...

Objective To compare tumor volume reduction rate (TVRR) measured by MR volumetry after preoperative chemoradiotherapy (CRT) and pathological tumor regression grade (TRG) in locally advanced rectal cancer (LARC). Material and methods In total, 20 patients with LARC (cT3-T4) treated with CRT followed by Total Mesorectal Excision (TME) between April 2011 and April 2013 were analyzed retrospectively. Pre- and post- CRT tumor volumes (MR volumetry) were measured on 3D MR sequences. TVRR was determined using the equation TVRR (%) = (pre-CRT tumor volume—post-CRT tumor volume) × 100/pre-CRT tumor volume. The downstaging (defined as ypT0-T2) of tumor mass was evaluated and the correlation between TVRR and TRG was calculated with the method proposed by Dworak using the Spearman rank test. Results The median TVRR was 77.3% (range, 26.4–99.3%); TVRR was >60% in 18 cases (90%) and in 8 of these patients (44.4 %) it was >80%. Downstaging of tumor lesions was obtained in 15 patients (75%). In 4 cases there was a complete tumor regression (TRG4) at histological examination and in the same patients there was also a TVRR > 80% measured by MR volumetry. A statistically significant correlation between TVRR and TRG ( r s = 0.5466, p = 0.0126) was observed. Conclusion TVRR after preoperative CRT correlates with TRG in LARC. The MR volumetry is a prognostic factor to estimate the tumor response after preoperative CRT. TVRR data may be an useful biomarker for tailoring surgery and postoperative adjuvant chemotherapy.

Aims and objectives Methods and materials Results Conclusion Personal information References, Aims and objectives: Aim of our study is to establish the role of virtopsy in the evaluation of lesion’s pattern, cause of death, and particularly in the recognition of dynamics of trauma, in victims of fatal motor-vehicle accidents. In motor-vehicle...

Points essentiels ● Moins pris en compte que les troubles cognitifs, les signes psychologiques et comportementaux de la maladie d’Alzheimer sont presents des le debut et a tous les stades de son evolution chez la plupart des patients. ● Il faut reperer ces signes des le debut, car ils orientent vers le diagnostic. Il s’agit de desordres affectifs et emotionnels, de signes psychotiques, de troubles des conduites instinctuelles et de troubles du comportement proprement dit. Pour les evaluer, il est fait essentiellement recours au questionnaire INP (inventaire neuropsychiatrique). ● Ils sont surtout lies aux atteintes neurobiologiques de la maladie ; mais ils peuvent, surtout s’ils sont aigus, repondre a de multiples etiologies, somatiques, iatrogenes, psychologiques et environ- nementales. ● Observes chez 80 % des patients, ils conditionnent l’evolution de la maladie. Source de souffrance et de baisse de qualite de vie pour le patient, premiere cause de detresse pour les aidants familiaux et par consequent d’hospitalisation et de placement, ils augmentent de fait le cout de la prise en soin. ● L’enjeu est de mieux les connaitre, pour mieux les traiter et surtout mieux les prevenir.

When psychological and behavioral disorders of Alzheimer's disease appear suddenly, somatic, iatrogenic and reactive or relational psychological causes must be ruled out or treated before concluding that the cause is lesional. Non-pharmacological interventions should be privileged for the prevention and management of behavioral manifestations of mild to moderate intensity: psychological support of the patient (short therapies), training the caregiver, work on daily habits, reorganization of the home, behavioral measures against apathy and especially agitation, rehabilitation strategies, and therapy involving music, light, aromas, etc. Pharmacological therapies are only moderately effective in these disorders. They must be targeted and follow a sequence of prescription that maximizes tolerance and distinguishes treatment of acute and chronic states. Anticholinesterase agents may be useful in this domain to prevent or ease some symptoms (especially apathy). The efficacy of memantine must be confirmed by additional data. Some selective serotonin reuptake inhibitors agents may be useful not only in depression but also anxiety, emotional disturbances, irritability and compulsiveness. Atypical neuroleptics are better tolerated than the classic ones. They are most effective in this context but must be reserved for specific indications and limited in time because of the increased risk of stroke. Other psychotropics (benzodiazepines, carbamates, antiepileptics) should be used cautiously in this context.

Resume Les symptomes comportementaux et psychologiques de la demence (SCPD) sont, avec les troubles cognitifs, une composante clinique majeure de la maladie d’Alzheimer et des pathologies apparentees. Leur reperage et leur connaissance sont essentiels pour la comprehension des mecanismes physiopathologiques de ces affections, pour l’evaluation de leurs consequences fonctionnelles sur le patient et les aidants, pour l’adaptation des differentes prises en charge. Un groupe de geriatres, neurologues et psychiatres francais specialises dans ce domaine (THEMA 2) ont elabore une mise au point epidemiologique, diagnostique et therapeutique sur les SCPD. La base de travail etait la Conference de Consensus publiee par l’International Psychogeriatric Association publiee en 2000. Ces recommandations ont fait l’objet d’une mise a jour a partir de la litterature et d’une adaptation a l’environnement francais, pour elaborer cette synthese validee par l’ensemble du groupe de consensus.

A total synthesis of rhizoxin D (1b), a 16-membered antitumoral macrolide, is reported. The strategy relies on the application of a Brown allylation reaction for the C 15 and C 16 asymmetric centres control. Installation of the C17 hydroxyl function with concomitant building of the (E)-C18-C19 double bond was effected by a diastereoselective addition of vinyllithium derivative 15 to aldehyde 10. The terminal enone group was then introduced to achieve the preparation of C11-C20 segment 23. A Heck coupling reaction between C11-C20 fragment 23 and C3-C10 segment 24 (previously prepared in our laboratory) was performed with success to deliver the C3-C20 fragment 25. The total synthesis of rhizoxin D (1b) was achieved after transformation of 25 into the macrolactone 28, and coupling the C21-C28 side chain using a Wittig-Wadsworth-Emmons reaction.

Item does not contain fulltext Mutations in the Forkhead box G1 (FOXG1) gene, a brain specific transcriptional factor, are responsible for the congenital variant of Rett syndrome. Until now FOXG1 point mutations have been reported in 12 Rett patients. Recently seven additional patients have been reported with a quite homogeneous severe phenotype designated as the FOXG1 syndrome. Here we describe two unrelated patients with a de novo FOXG1 point mutation, p.Gln46X and p.Tyr400X, respectively, having a milder phenotype and sharing a distinctive facial appearance. Although FoxG1 action depends critically on its binding to chromatin, very little is known about the dynamics of this process. Using fluorescence recovery after photobleaching, we showed that most of the GFP-FoxG1 fusion protein associates reversibly to chromatin whereas the remaining fraction is bound irreversibly. Furthermore, we showed that the two pathologic derivatives of FoxG1 described in this paper present a dramatic alteration in chromatin affinity and irreversibly bound fraction in comparison with Ser323fsX325 mutant (associated with a severe phenotype) and wild type Foxg1 protein. Our observations suggest that alterations in the kinetics of FoxG1 binding to chromatin might contribute to the pathological effects of FOXG1 mutations.

A synthetic approach to the eastern part of spiramycin, an important antibiotic compound, is described. Introduction of the side chain was first envisaged through a Hoppe aldehyde allylation. This reaction was carried outbetween an optically pure aldehyde 32 and a (′)-γ-alkoxy allyltitanium(IV) species derived from a primary γ-alkoxy allyl (diisopropyl)carbamate. Under kinetic resolution conditions, the anti-Cram compound 35 was obtained in an 80:20 mixture, with the Cram isomer 34, in 81% yield. Employing the optically pure (S)-γ-alkoxy allyl (diisopropyl)carbamate 36, the corresponding (R)-γ-alkoxy allyltitanium (R)-'Ti'-III was generated under n-BuLi.TMEDA/Ti(Oi-Pr) 4 conditions, that reacted with aldehyde 32 in double stereodifferentiation to deliver the expected Cram compound 40 in 80% yield (95% de). This latter corresponded to the C1-C7 fragment of spiramycin.

An efficient access to optically active (R)- or (S)-γ-alkoxy allyltitanium(IV) intermediates, in aldehyde allylation reactions, is described. Enantiomeric γ-alkoxy secondary allyl carbamates (R)- and (S)-14 were first prepared. Determination of their enantiomeric excess was realised on the corresponding deuterated isotopic derivatives by NMR in chiral liquid media. Subsequent aldehyde allylation reaction with propanal performed under Hoppe n-BuLi.(-)-sparteine/Ti(Oi-Pr) 4 or n-BuLi.TMEDA/Ti(Oi-Pr) 4 conditions, led to both enantiomeric homoallylic alcohols 15 or ent-15 in 90% yield, 100% ed and 80% ee.

Resume Les etats delirants du sujet âge sont en majorite lies a des etiologies dementielles. L’environnement a un impact important sur la survenue et l’entretien des troubles : attitudes de l’entourage, organisation de vie et architecture. Il est possible d’agir sur ces parametres a domicile ou en institution dans le but d’augmenter la qualite de vie des patients. Les objectifs sont : ameliorer l’orientation dans la realite, reduire les consequences comportementales du delire en securisant le lieu de vie, prevenir les troubles par des strategies comportementales, aider les aidants et soignants a nuancer leurs attitudes, favoriser l’expression de la souffrance des patients par des approches psychotherapeutiques ou a mediation.

Resume La clinique des etats delirants du sujet âge demeure mal connue. Elle peut etre caracterisee par l’âge de survenue : psychoses vieillies et delires de survenue tardive (apres 60 ans) ; mais aussi par l’etiologie : psychoses dites fonctionnelles et psychoses associees a une affection organique. On soulignera la prevalence importante des delires associes a des demences de type Alzheimer ou autre, puis viennent les etats thymiques delirants, les psychoses schizophreniques ou non schizophreniques, les delires lies a des troubles cerebrovasculaires ou a des desafferentations sensorielles. Tout trouble delirant survenant de novo apres 65 ans doit faire evoquer une deterioration sous-jacente Les consequences comportementales du delire (agitation, agressivite) en font la gravite. Le diagnostic differentiel se fait essentiellement avec la confusion mentale. Les elements predisposant au delire dans ce contexte peuvent etre d’ordre genetique suspectes dans certains cas, et de facon habituelle : une comorbidite somatique, l’isolement social, les deficits sensoriels, les troubles cognitifs, la polymedication, ou l’abus de toxiques. De plus, la confrontation au vieillir rend vulnerable aux decompensations psychiques, avec pour caracteristique que les processus depressifs et delirants deviennent a cet âge tres intriques. L’evaluation sera realisee grâce a des echelles specifiques aux psychoses (SANSS, PANSS, PDI), ou a des echelles globales dans le cas de la demence (NPI). Le traitement associe toujours des mesures non pharmacologiques. Le traitement medicamenteux sera etiologique et si besoin symptomatique.

The synthesis of the S1-N10 nine-membered lactone core 28 of ent-griseoviridin is reported. Starting from cystine derivative 25, encompassing a terminal ynoate, treatment under Zn/ AcOH conditions led to the formation of lactone 28 in 12% yield. Therefore, the lactone moiety of ent-griseoviridin is obtained in 10.7% overall yield for two steps. An access to the corresponding 5-epi-griseoviridin lactone 29 is also described.

During the summer of 2001, 2-year-old Fraxinus excelsior and Fagus sylvatica plants were subjected to ozone-rich environmental conditions at the Regional Forest Nursery at Curno (Northern Italy). Atmospheric ozone concentrations and stomatal conductance were measured, in order to calculate the foliar fluxes by means of a one-dimensional model. The foliar structure of both species was examined (thickness of the lamina and of the individual tissues, leaf mass per area, leaf density) and chlorophyll a fluorescence was determined as a response parameter. Stomatal conductance was always greater in Fraxinus excelsior, as was ozone uptake, although the highest absorption peaks did not match the peaks of ozone concentration in the atmosphere. The foliar structure can help explain this phenomenon: Fraxinus excelsior has a thicker mesophyll than Fagus sylvatica (indicating a greater photosynthesis potential) and a reduced foliar density. This last parameter, related to the apoplastic fraction, suggests a greater ability to disseminate the gases within the leaf as well as a greater potential detoxifying capacity. As foliar symptoms spread, the parameters relating to chlorophyll a fluorescence also change. PI (Performance Index, Strasser, A., Srivastava, A., Tsimilli-Michael, M., 2000. The fluorescence transient as a tool to characterize and screen photosynthetic samples. In: Yunus, M., Pathre, U., Mohanty, P., (Eds.) Probing Photosynthesis: Mechanisms, Regulation and Adaptation. Taylor & Francis, London, UK, pp. 445-483.) has proved to be a more suitable index than Fv/Fm (Quantum Yield Efficiency) to record the onset of stress conditions.

International audience; A (Z)-vinyl (N,N-diisopropyl)carbamate treated with Grignard reagents, under Wenkert Nickel-catalyzed conditions, gave an access to several substituted (Z)-alkenyl derivatives. These Nickel-catalyzed reactions, carried out with vinyl-, phenyl-, p-methoxyphenyl-, trimethylsilylmethylmagnesium bromide and benzylmagnesium chloride, led to the corresponding (Z)-alkenyl derivatives in good yields and high stereoselectivities.

11 páginas., Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular clusters. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices $(0.7 < \Gamma

Il Corso Sperimentale di Teoria e Analisi tenuto al Conservatorio “Arcangelo Corelli” di Messina da Mario Musumeci compie in quest’anno accademico 1999/2000 il suo dodicesimo anno di età. Il corso gode di ottima salute ed è oggi uno dei fiori all’occhiello del Conservatorio messinese. Soprattutto rappresenta per gli allievi un punto fermo per l’adeguata comprensione del linguaggio musicale: subito messi di fronte al testo musicale, sono obbligati, di volta in volta, ad interagire attivamente con esso prendendo in considerazione tutti i suoi parametri, scomponendolo e ricomponendolo, anche con l’uso creativo e innovativo della corrupta lectio (la prassi del modificare l’oggetto in analisi per conferirgli una più precisa identità).

In this paper we show that long-run expectations about future housing prices of both households and, especially, financial intermediaries had a large impact on households' indebtedness during the recent boom in U.S. housing prices. We introduce the theory of natural expectations in a collateralized credit market model populated by households and banks and find: (1) that mild variations in long-run forecasts of housing prices result in large differences in the amount of home equity extracted during the boom; and (2) that the equilibrium level of debt and the interest rate are particularly sensitive to financial intermediaries' naturalness.