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The Human Variome Project (HVP) is an international effort aiming systematically to collect and share information on all human genetic variants. It has been working for years in collaboration with local scientific societies by establishing systems to collect every genetic variant reported in a country and to store these variants within a database repository: LOVD (Argentinian chapter: ar.lovd.org). Formally established in 2017 in the Argentinian Node, up to June 2019 we collected more than 25,000 genetic variants deposited by 17 different laboratories. Nowadays the HVP country nodes represent more than 30 countries. In Latin America there are four country nodes: Argentina, Brazil, Mexico and Venezuela; the first two interacted recently launching the LatinGen database. In the present work we want to share our experience in applying the HVP project focusing on its organization, rules and nomenclature to reach the goal of sharing genetic variants and depositing them in the Leiden Open Variation Database. Contributing laboratories are seeking to share variant data to gain access all over the country. It is one of our goals to stimulate the highest quality by organizing courses, applying current nomenclature rules, sponsoring lectures in national congresses, distributing newsletter to serve the Argentinian genomics community and to stimulate the interaction among Latin America countries. El Proyecto Varioma Humano (HVP) es un esfuerzo internacional que tiene como objetivo recopilar y compartir sistemáticamente información sobre todas las variantes genéticas humanas. Hemos estado trabajando durante tres años en colaboración con sociedades científicas locales, mediante el establecimiento de sistemas para recolectar todas las variantes genéticas reportadas en el país y almacenarlas dentro de la base de datos LOVD (capítulo argentino: ar.lovd.org). En el año 2017 fue establecido formalmente el Nodo Argentino del HVP, habiéndose recolectado más de 25.000 variantes genéticas depositadas por 17 laboratorios diferentes hasta junio de 2019. Hoy en día existen al menos 30 nodos del HVP, correspondientes a diferentes países. En América Latina hay cuatro nodos: Argentina, Brasil, México y Venezuela; Los dos primeros interactuaron recientemente lanzando la base de datos LatinGen. En el presente trabajo queremos compartir nuestra experiencia en la aplicación del proyecto HVP centrándonos en su organización, reglas y nomenclatura para alcanzar el objetivo de compartir variantes genéticas y depositarlas en la base de datos de variaciones abiertas de Leiden (LOVD). Es uno de nuestros objetivos estimular la más alta calidad mediante la organización de cursos, aplicación de las reglas de nomenclatura actuales, patrocinio de conferencias en congresos nacionales, distribución de boletines informativos para la comunidad de genómica argentina, y estimulación de la interacción entre los países de América Latina.

Small-scale kinetic processes associated with turbulence, plasma instabilities, magnetic reconnection, etc., play a major role in dissipating energy and governing the large-scale evolution of the solar wind. However, a general impediment to improving the understanding of the kinetic physics of the solar wind is in the limitations on measurement cadences of particle instruments, which are usually several orders of magnitude below the equivalent cadences of field instruments. Nevertheless, knowledge of the details of the particle velocity distribution functions (VDFs) at sub-second cadence is required to make progress in this area. This is particularly true for the electron VDFs, which play a significant role in the overall energetics of the solar wind through their transmission of heat flux from the Sun. In this paper, we detail and illustrate a novel measurement scheme deployed on Solar Orbiter’s Solar Wind Analyser Electron Analyser System (SWA-EAS), which allows for 2D pitch angle distributions (PAD) to be returned over short periods (5–10 min) at a cadence of 0.125 s. This is achieved through the use of a B-field vector shared by the magnetometer (MAG) instrument to steer the SWA-EAS system to record only that part of the full SWA-EAS field-of-view needed to construct the PAD. We provide an example of early observations using this scheme to illustrate that it is working well. Given that the electrons are usually gyrotropic, these measurements provide a new tool with which to derive details of the electron VDFs at high cadence for the study of the solar wind’s kinetic processes.

Gene/s sequencing in hereditary breast/ovary cancer (HBOC) in routine diagnosis is challenged by the analysis of panels. We aim to report a retrospective analysis of BRCA1/2 and non-BRCA gene sequencing in patients with breast/ovary cancer (BOC), including triple-negative breast cancer (TNBC), in our population. In total 2155 BOC patients (1900 analyzed in BRCA1/2 and 255 by multigenic panels) gave 372 (17.2.6%) and 107 (24.1%) likely pathogenic/pathogenic variants (LPVs/PVs), including BRCA and non-BRCA genes, for the total and TNBC patients, respectively. When BOC was present in the same proband, a 51.3% rate was found for LPVs/PVs in BRCA1/2. Most of the LPVs/PVs in the panels were in BRCA1/2, non-BRCA gene LPVs/PVs were in CDH1, CHEK2, CDKN2A, MUTYH, NBN, RAD51D, and TP53. TNBC is associated with BRCA1/2 at a higher rate than the rest of the breast cancer types. The more prevalent PVs in BRCA1/2 genes (mostly in BRCA1) do not rule out the importance to panels of genes, although they are certainly far from shedding light on the gap of the 85% predicted linkage association of BOC with BRCA1/2 and are still not elucidated.

The Solar Orbiter mission seeks to make connections between the physical processes occurring at the Sun or in the solar corona and the nature of the solar wind created by those processes which is subsequently observed at the spacecraft. The mission also targets physical processes occurring in the solar wind itself during its journey from its source to the spacecraft. To meet the specific mission science goals, Solar Orbiter will be equipped with both remote-sensing and in-situ instruments which will make unprecedented measurements of the solar atmosphere and the inner heliosphere. A crucial set of measurements will be provided by the Solar Wind Analyser (SWA) suite of instruments. This suite consists of an Electron Analyser System (SWA-EAS), a Proton and Alpha particle Sensor (SWA-PAS), and a Heavy Ion Sensor (SWA-HIS) which are jointly served by a central control and data processing unit (SWA-DPU). Together these sensors will measure and categorise the vast majority of thermal and suprathermal ions and electrons in the solar wind and determine the abundances and charge states of the heavy ion populations. The three sensors in the SWA suite are each based on the top hat electrostatic analyser concept, which has been deployed on numerous space plasma missions. The SWA-EAS uses two such heads, each of which have 360° azimuth acceptance angles and ±45° aperture deflection plates. Together these two sensors, which are mounted on the end of the boom, will cover a full sky field-of-view (FoV) (except for blockages by the spacecraft and its appendages) and measure the full 3D velocity distribution function (VDF) of solar wind electrons in the energy range of a few eV to ∼5 keV. The SWA-PAS instrument also uses an electrostatic analyser with a more confined FoV (−24° to +42° × ±22.5° around the expected solar wind arrival direction), which nevertheless is capable of measuring the full 3D VDF of the protons and alpha particles arriving at the instrument in the energy range from 200 eV/q to 20 keV/e. Finally, SWA-HIS measures the composition and 3D VDFs of heavy ions in the bulk solar wind as well as those of the major constituents in the suprathermal energy range and those of pick-up ions. The sensor resolves the full 3D VDFs of the prominent heavy ions at a resolution of 5 min in normal mode and 30 s in burst mode. Additionally, SWA-HIS measures 3D VDFs of alpha particles at a 4 s resolution in burst mode. Measurements are over a FoV of −33° to +66° × ±20° around the expected solar wind arrival direction and at energies up to 80 keV/e. The mass resolution (m/Δm) is > 5. This paper describes how the three SWA scientific sensors, as delivered to the spacecraft, meet or exceed the performance requirements originally set out to achieve the mission’s science goals. We describe the motivation and specific requirements for each of the three sensors within the SWA suite, their expected science results, their main characteristics, and their operation through the central SWA-DPU. We describe the combined data products that we expect to return from the suite and provide to the Solar Orbiter Archive for use in scientific analyses by members of the wider solar and heliospheric communities. These unique data products will help reveal the nature of the solar wind as a function of both heliocentric distance and solar latitude. Indeed, SWA-HIS measurements of solar wind composition will be the first such measurements made in the inner heliosphere. The SWA data are crucial to efforts to link the in situ measurements of the solar wind made at the spacecraft with remote observations of candidate source regions. This is a novel aspect of the mission which will lead to significant advances in our understanding of the mechanisms accelerating and heating the solar wind, driving eruptions and other transient phenomena on the Sun, and controlling the injection, acceleration, and transport of the energetic particles in the heliosphere.

Background: Ovarian cancer is the leading cause of death worldwide among gynecologic malignancies. The recent approval of inhibitors of poly (ADP-ribose) polymerase (iPARP) in the treatment of ovarian cancer in the presence of a BRCA1/2 mutation has sparked the analysis of women with such diagnosis, which can further benefit from the detection of carriers in the family. Germline sequence and large rearrangements for BRCA1/2 were tested in 398 consecutive epithelial ovarian cancer (EOC) patients. The aim of this study was to identify the frequency and spectrum of germline BRCA1/2 pathogenic alterations in a cohort of patients with ovarian serous carcinoma, with a view to adequately selecting patients for prevention through family counseling and correlating this frequency with platinum sensitivity as a guidance to identify patients eligible for iPARP in our population. Results: A total of 96 patients carried a pathogenic germline mutation, accounting for an overall 24.1% mutation incidence. Among mutation carriers, BRCA1 showed 62.5% incidence, BRCA2 rendered 36.5%, and one patient exhibited a mutation in both genes. Three pathogenic mutations were recurrent mutations detected five, three, and four times and represented 12.5% of the mutated samples. Worth highlighting, a 50% mutation incidence was detected when breast and ovarian cancer coexisted in the same patient. Novel mutations amounted to 9.4% of the total mutations, as compared to 4.7% in breast cancer. Forty out of 60 BRCA1 mutations were beyond the ovarian cancer cluster region (OCCR), in stark contrast with 22 out of 36 BRCA2 mutations being inside the OCCR. Taken together, germline BRCA1/2 mutations in EOC patients showed a distinct mutational spectrum compared to our previously published data on breast cancer patients. Conclusions: In sum, our study provides novel data on ovarian BRCA1/2 mutation prevalence worldwide, enhances adequate patient selection for family counseling and prevention, and sheds light on the benefits of iPARP treatment. Fil: Cardozo, Florencia C.. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina Fil: Goncalves, Susana. AstraZeneca Argentina MC; Argentina Fil: Mele, Pablo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Liria, Natalia C.. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina Fil: Sganga, Leonardo. AstraZeneca Argentina MC; Argentina Fil: Diaz Perez, Ignacio. AstraZeneca Argentina MC; Argentina Fil: Podesta, Ernesto Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Podesta, Ernesto Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina

In Ashkenazi Jewish (AJ) high risk families 3 mutations [2 in BRCA1 (c. 68_69del and c.5266dup) and 1 in BRCA2 (c.5946del)] account for the majority of high risk breast and ovarian cancer cases in that ethnic group. Few studies with limited number of genotyped individuals have expanded the spectrum of mutations in both BRCA genes beyond the 3 mutation panel. In this study, 279 high risk individual AJ were counseled at CEMIC (Centro de Educación Médica e Investigaciones Clínicas), and were genotyped first for the 3 recurrent mutation panel followed by Next Generation Sequencing (NGS) of BRCA1 BRCA2 in 76 individuals who tested negative for the first genotyping step. Of 279 probands (259 women), 55 (50 women) harbored one of the 3 mutations (19.7%); Of 76 fully sequenced cases (73 women), 6 (5 women) (7.9%) carried a pathogenic mutation: in BRCA1, c.2728C > T - p.(Gln910*); c.5407-?_(*1_?)del and c.5445G > A - p.(Trp1815*); in BRCA2, c.5351dup - p.(Asn1784Lysfs*3); c.7308del - p.(Asn2436Lysfs*33) and c.9026_9030del - p.(Tyr3009Serfs*7). Of 61 mutation carriers the distribution was as follows: 11 cancer free at the time of genotyping, 34 female breast cancer cases with age range 28-72 years (41.6 ± 9.3), 3 male breast cancer cases with age range 59-75 years (65 ± 7.3), 6 breast and ovarian cancer cases with age range 35-60 years (breast 40.4 ± 5.2; ovary 47.8 ± 7.2) and 7 ovarian cancer cases with age range 41-77 years (60.6 ± 13.3). This information proved highly useful for counseling, treatment, and prevention for the patient and the family. In conclusion comprehensive BRCA1/2 testing in AJ high risk breast ovarian cancer cases adds valuable clinically relevant information in a subset of cases estimated up to 7% and is therefore recommended. Fil: Solano, Angela Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina Fil: Liria, Natalia C.. Centro de Educación Medica E Invest.clinicas; Argentina Fil: Jalil, Fernanda. Centro de Educación Medica E Invest.clinicas; Argentina Fil: Faggionato, Daniela. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina Fil: Mele, Pablo G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Mampel, Alejandra. Universidad Nacional de Cuyo; Argentina Fil: Cardoso, Florencia C.. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina Fil: Podesta, Ernesto J.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina

Background: A perceived risk of time-limited emergency department (ED) assessment of patients is inadequate workup leading to inappropriate disposition. The aim of this study was to examine the association of time to disposition plan (TDP) on ED length of stay (LOS) and correlate this to mortality. Methods: A retrospective review of data collected from ED information systems at three hospitals was conducted between June 2008 and October 2009. Included patients were admitted to a general medical unit. Patients were excluded if admitted to intensive care, coronary care, a cardiac monitored bed or required surgery in first 24 h or had an expected LOS of

Rehabilitative treatment of discal herniation has different goals: pain control, back stabilization, improvement of active motility and quality of life. In order to achieve them we can apply different methods, like physical therapies, manual therapies, kynesitherapy and water kynesitherapy, global postural reeducation and patient’s education.

Background and aims: The FIMP-MCRN, member of ENCePP (European Network of Centres of Pharmacoepidemiology and Pharmacovigilance), was established in 2003 with the aim of developing competence, infrastructure, networking and education for paediatric clinical trials. It involves more than 6000 Italian Family Paediatricians (FPI) and it can survey more than 6.000.000 Italian children from 0 to 14 years. It's on the point of becoming member of ENPREMA (European Network Paediatric Research at the EMA). Methods: The FIMP - MCRN have developed and improved its expertise in Phase 3 and 4 clinical trials. It has got a Quality Control, a Quality Assurance and a traceability, a transparency and a data safety. Ad hoc training programs have incremented knowledge about clinical trials in FPI to build up the necessary competencies. Results: A significant role can be played by the FPI with the participation to active pharmacovigilance projects. The primary objective of FIMP- Antibiotics Tolerability Profile Study (FIMP-ATPS) was to assess in patients with pharyngotonsillitis (FT) and rhinosinusitis (RS) the antibiotic tolerability profile after the days of administration. A different, more proactive, approach is needed to use of disease databases[ FIMP-Dumbo Othitis Study (more than 400 children included)] and FPISentinel Influence A (H1N1) Survey [including possible ADRs after vaccination]. In epiweek 45 the incidence of H1N1 was 28,19 (0-4 yr) and 40.78 (5- 14 yr) cases per 1.000. Conclusions: Networking is mandatory to build up the necessary competencies, to facilitate cooperation, to share the skills and expertise and to avoid duplication of studies.

The effect of long-term treatment with phenobarbitone on pituitary responsiveness to gonadotrophin-releasing hormone and thyrotrophin-releasing hormone was studied in 20 boys being treated with the drug to prevent febrile convulsions. Baseline concentrations of luteinising and follicle-stimulating hormones were reduced as well as the responses of these hormones to stimulation with gonadotrophin-releasing hormone. Baseline prolactin concentrations were raised in comparison with those in normal children. The response of prolactin to thyrotrophin-releasing hormone, however, was impaired only in the children who had been receiving the drug for a long time. Phenobarbitone had no effect on the secretion of growth hormone. Further studies should be carried out to ascertain how long these effects on pituitary function last after phenobarbitone is withdrawn and whether this interference with pituitary function modifies the child's subsequent development.

Beta2microglobulin (B2m) has been shown play a causal role in amyloidosis of long term hemodialyzed patients. Many authors demonstrated that increased levels of B2m and amyloid deposition are dire ctly correlated with the use of cuprophane dialysis membranes (1). This findings led several authors to study the capacity of different membranes to generate or to remove this protein (2). Less is known about the behaviour of B2m in CRF patients beginning hemodialysis treatment. The purpose of this study is to compare B2m in patients dropped out conservative therapy with artificial diet supplemented with ketoanalogues and essential aminoacids (AD) (3), beginning different types of blood depuration, monthly until six months.

53 newborn infants with both G-6-PD deficiency (29 male hemizygotes and 24 female heterozygotes) and alpha-thalassaemia, and 120 newborn infants with only the enzymatic defect (60 male hemizygotes and 60 female heterozygotes) were studied. 12 of those with both G-6-PD deficiency and alpha=thalassaemia, and 32 of those with only G-6-PD deficiency showed hyperbilirubinaemia. alpha-Thalassaemia does not seem to be implicated in the development of hyperbilirubinaemia in G-6-PD-deficient newborns.

Summary: The behavior of the free fraction of valproic acid (VPA) was evaluated during long-term treatment of 24 children (9–18 months of age) with febrile convulsions. A series of relevant hematological parameters was monitored for the entire observation period (12 months). VPA plasma levels ranged from 54.3 ± 26 to 66.6 ± 32.8 (μg/ml. The unbound fraction of the drug was determined in tears, which has been shown to be the best practical indicator of the free portion of an anticonvulsant drug, and ranged from 5.1 ± 4.0 to 6.1 ± 4.3 μg/ml. The tear/plasma ratio (and hence the free/total ratio) ranged from 9.3 to 9.7, in agreement with literature data. No significant variations of VPA plasma and tear levels, and therefore of the tear/plasma ratios, were ever observed. The hematological data revealed no significant alterations during the entire observation time, although some of the variables did fluctuate. Side effects were mild and temporary. The present report indicates that VPA has no particular toxic effect in young children treated for the prevention of febrile convulsions. RESUME La fraction libre du VPA a eteevaluee pendant un traitement a long terme chez 24 enfants (âges de 9 a 18 mois) atteints de convulsions febriles. Une serie de parametres hematologiques ont eteetudies pendant la periode ďobservation (12 mois). Les taux plasmatiques de VPA etaient de 54,3 ± 26 a 66,6 ± 32,8 μg/ml. La fraction libre a ete determinee dans les larmes, les-quelles se sont montrees etre le meilleur indicateur pratique de la fraction libre ďun anticonvulsivant et son taux etait de 5,1 ± 4,0 a 6,1 ± 4,3 μg/ml. Le rapport larme/plasma (et done libre/ total) etait entre 9,3 et 9,7 en agrement avec les donnees de la litterature. Il n'a pas ete observe de variations significatives des taux plasmatiques ou dans les larmes, ni dans le rapport larmes/ plasma. Les donnees hematologiques n'ont pas montreďalter-ations significatives pendant toute la periode ďobservation qu-oique quelques fluctuations de certaines variables aient pu se produire. Les effets collateraux ont ete legers et temporaires. Le present travail indique que le VPA n'a pas ďeffet toxique particulier chez les petits enfants traites en vue de la prEvention des convulsions febriles. RESUMEN Durante un tratamiento prolongado de 24 ninos (edades entre 9 y 18 meses) con convulsiones febriles, se ha evaluado el com-portamiento de la fraccion libre del acido valproico (VPA). Par-alelamente se monitorizo una serie de parametros hematologicos relevantes durante todo el periodo de observacion de 12 meses. Los niveles plasmaticos de VPA oscilaron de 54.3 ± 26 a 66.6 ± 32.9 μ-g/ml. La fraccion on ligada de la droga fue determinada en las lagrimas, que ha demostrado ser el indicador mejor y mas practico de la porcion libre de las medicaciones anticonvulsivas; sus valores oscilaron entre 5.1 ± 4.0 y 6.1 ± 4.3 μg/ml. La relacion lagrima/plasma (y por lo tanto la relacion libre/total) vario entre 9.3 y 9.7, en acuerdo con los datos de la literatura. No se observaron variaciones significativas de los niveles en plasma y lagrimas en lo que se refiere a relacion lagrimas/plasma. La informacion hematologica no revelo alteraciones significativas durante todo el tiempo de observacion, aunque aparecieron algunas fluctuaciones en ciertas variables. Esta comunicacion indica que el VPA no tiene efectos toxicos especificos en ninos pequenos tratados para prevenir ataques febriles. ZUSAMMENFASSUNG Untersuchung der freien Fraktion der Valproinsaure (VPA) wahrend der Langzeitbehandlung von 24 Kindern (9 bis 18 Monate alt) mit Fieberkrampfen. Parallel dazu wurde eine Reihe relevanter hamatologischer Parameter wahrend der gesamten Beobachtungszeit (12 Monate) mitbestimmt. Die VPA-Plasma-spiegel erstreckten sich von 54,3 ± 26 bis 66,6 ± 32,8 μg/ml. Der freie Medikamentenanteil wurde in der Tranenflussigkeit bestimmt, die bewiesenermasen der praktisch beste Indikatior des freien Anteils eines Antikonvulsivums darstellt. Dieser An-teil schwankte zwischen 5,1 ± 4,0 und 6,1 ± 4,3 μ-g/ml. Der Quotient Tranenflussigkeit/Plasma (und damit die Relation freier Anteil zum Gesamt) betrug 9,3 bis 9,7 und befindet sich somit in Ubereinstimmung mit den Daten der Literatur. Signifikante Variationen der VPA Plasma und Tranenflussigkeitsspiegel oder der Tranenflussigkeit-Plasma-Quotienten wurden nie beo-bachtet. Die hamatologischen Daten liesen wahrend der gesamten Beobachtungszeit keine signifikanten Veranderungen er-kennen, obwohl gewisse Fluktuationen einzelner Variabler er-folgten. Nebenwirkungen traten in milder und vorubergehender Form auf. Die Mitteilung zeigt. Das VPA keinen besonders tox-ischen Effekt kleinen Kindern gegenuber aufweist, die zur Ver-hutung von Fieberkrampfen behandelt werden.

A 29-year-old white female with longstanding classical rheumatoid arthritis (RA) developed clinical and serological manifestations of systemic lupus erythematosus (SLE) with prominent signs of diffuse proliferative lupus nephritis. She fulfilled the ARA criteria for the classification of SLE as well as the ARA criteria for classical RA. The concomitant presence of these two affections in the same patient is rare and the discriminating features suggest that this coexistence may be coincidental. With respect to treatment, our patient had good relief of symptoms by a combined administration of methylprednisolone pulses and cyclophosphamide.

1 Luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin levels were measured in twenty paediatric patients receiving sodium valproate (30 mg/kg body weight daily) and in ten control subjects under control conditions and following LRH-TRH administration. In addition, baseline GH levels were measured in the two groups. 2 No significant differences were observed between the basal and stimulated hormone levels in the two groups. Although sodium valproate may act as anticonvulsant by increasing GABA levels in the central nervous system, the present data indicate that a central GABAergic pathway is probably not involved in the control of gonadotrophin and prolactin secretion.

The aim of this study was to pilot a program to encourage shift breaks for emergency department doctors and analyse the effects of breaks on tiredness and fatigue as well as possible effects on overall departmental performance. During Phase 1, medical staff were asked to fill out a survey regarding their working day at the end of every shift. A 30-minute uninterrupted break was promoted during Phase 2 by provision of a cover doctor on the roster as well as educational sessions and posters. There were 233 completed surveys received over the 4-week period. Only 33% of shifts worked included an uninterrupted break in Phase 1, which improved significantly to 60% during Phase 2. Subjective tiredness was significantly lower at the end of a shift when a break was taken (P < 0.001), while fatigue levels were also lower, but not significant (P = 0.060). There were significant improvements in some key performance indicators.

A major challenge for Local Governments today is represented by the introduction of new networked service delivery models able to coordinate a number of different local actors for responding effectively to increasing community's expectations. Information and Communication Technologies (ICTs) are instrumental here. Though, the implementation of ICTs in Local Government Agencies (LGA) is a challenge too. That's why effective new services delivery models and successful adoption of enabling ICTs within the LGA goes hand-in-hand. Following these considerations, this paper aims at illustrating a case of ICT-based solutions adoption into a Local Government Agency in charge of tourism promotion. More specifically the e-business case methodology crafted and used for this purpose will be shown. In doing so, the role of the e-business case will be advocated both as a tool to accompany Local Government Agencies into the process of introducing and using ICTs, both as a starting point for a wider strategy aimed at modernizing local communities though ICTs. © 2010 ACM.

Two patients with acute promyelocytic leukemia (APL) relapsed at 111 and 84 months after achievement of complete remission (CR) induced by a combination of all- trans retinoic acid and chemotherapy. In both patients molecular remission, obtained after consolidation, had been confirmed at 60 months from CR achievement. At relapse, morphological, immunophenotypic, cytogenetic, and molecular analyses showed findings identical to those at diagnosis. Hematological and molecular remission was induced with the identical treatment applied at diagnosis. We conclude that, although infrequently, patients with APL treated with modern combination therapy can experience very late relapse and can be rescued with treatment similar to that administered at diagnosis.