Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: updated time-to-events results and prognostic factors for time to progression

New treatment options offering enhanced activity in elderly, newly diagnosed patients with multiple myeloma are required. One strategy is to combine melphalan and prednisone with novel agents. We previously reported an 89% response rate, including 32% complete responses and 11% near complete responses, in our phase 1/2 study of bortezomib plus melphalan and prednisone (VMP) in 60 newly diagnosed multiple myeloma patients with a median age of 75 years. Here, we report updated time-to-events data and the impact of poor prognosis factors on outcome

Crecimiento y contenido bioquímico comparativo de larvas en postflexión de sardina de tres zonas del Mediterráneo Occidental (Ebro, bahías de Almaría y Málaga)

Late larval stages of sardine (16-23 mm) were sampled during the 2003 spawning season in their nursery grounds located off the Ebro river mouth, on the Catalan coast, and in two bays of the Alborán Sea coasts, the Bay of Almería and the Bay of Málaga. The daily growth analysis of each sampled population revealed faster growth in the Ebro sardine larvae than in both of the Alboran Sea larval populations. This fact is supported by their greater content with age of DNA, RNA and protein. However, the significantly higher carbohydrate content of the Bay of Almería sardine larvae and a higher Fulton’s index, indicative of energy storage of individuals, in both of the sardine populations sampled in the Bays of Almería and Málaga show evident differences in the daily growth of the Alborán Sea larvae from those originating in the Ebro region. Late larval growth in the Alborán Sea sardine tends to favour an increase in body mass rather than in body length. This study hypothesises that the productivity pulses off the Alboran Sea coasts induced by the north and northwestern wind regimes may be responsible for the growth pulses observed in the otolith microstructure.Estados avanzados de larvas de sardina (de 16 a 23 mm) fueron muestreados durante el invierno de 2003 en zonas de alevinaje situadas en la desembocadura del río Ebro, en la costa catalana, y en las bahías de Almería y de Málaga, en las costas del Mar de Alborán. El análisis del crecimiento diario de cada población larvaria muestreada, evidencia un mayor crecimiento en las larvas procedentes del Ebro respecto a las nacidas en el Mar de Alborán. Esta observación se corrobora con un mayor incremento con la edad de los contenidos en DNA, RNA y proteínas de la población larvaria de sardina del río Ebro. Sin embargo, un contenido significativamente mayor de carbohidratos en la población de Almería, así como un mayor índice de Fulton, indicador de energía almacenada en un individuo, en ambas poblaciones del Mar de Alborán, evidencia una estrategia diferenciada de crecimiento de estas poblaciones larvarias con respecto a las procedentes del río Ebro. En consecuencia, las larvas de sardina del Mar de Alborán muestran una tendencia a crecer más en masa que en longitud, como lo evidencia el crecimiento relativo del peso seco, DNA, RNA y proteínas en relación con su longitud estándar. En este estudio se plantea la hipótesis de que los pulsos productivos en el Mar de Alborán, inducidos por el régimen de vientos de norte y poniente, pueden ser responsables de los pulsos de crecimiento larvario, como se evidencia en las microestructuras de los otolitos

<i>Gaia</i> Data Release 1. Summary of the astrometric, photometric, and survey properties

Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ∼3000 Cepheid and RR-Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr−1 for the proper motions. A systematic component of ∼0.3 mas should be added to the parallax uncertainties. For the subset of ∼94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr−1. For the secondary astrometric data set, the typical uncertainty of the positions is ∼10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ∼0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data

Anomaly-based exploratory analysis and detection of exploits in android mediaserver

Smartphone platforms are becoming increasingly complex, which gives way to software vulnerabilities difficult to identify and that might allow malware developers to gain unauthorised privileges through technical exploitation. However, the authors maintain that these types of attacks indirectly renders a number of unexpected behaviours in the system that can be profiled. In this work, the authors present CoME , an anomaly-based methodology aiming at detecting software exploitation in Android systems. CoME models the normal behaviour of a given software component or service and it is capable of identifying any unanticipated behaviour. To this end, they first monitor the normal operation of a given exploitable component through lightweight virtual introspection. Then, they use a multivariate analysis approach to estimate the normality model and detect anomalies. They evaluate their system against one of the most critical vulnerable and widely exploited services in Android, i.e. the mediaserver. Results show that the proposed approach can not only provide a meaningful explanatory of discriminant features for illegitimate activities, but can also be used to accurately detect malicious software exploitations at runtime

Anomaly-based exploratory analysis and detection of exploits in android mediaserver

Smartphone platforms are becoming increasingly complex, which gives way to software vulnerabilities difficult to identify and that might allow malware developers to gain unauthorised privileges through technical exploitation. However, the authors maintain that these types of attacks indirectly renders a number of unexpected behaviours in the system that can be profiled. In this work, the authors present CoME , an anomaly-based methodology aiming at detecting software exploitation in Android systems. CoME models the normal behaviour of a given software component or service and it is capable of identifying any unanticipated behaviour. To this end, they first monitor the normal operation of a given exploitable component through lightweight virtual introspection. Then, they use a multivariate analysis approach to estimate the normality model and detect anomalies. They evaluate their system against one of the most critical vulnerable and widely exploited services in Android, i.e. the mediaserver. Results show that the proposed approach can not only provide a meaningful explanatory of discriminant features for illegitimate activities, but can also be used to accurately detect malicious software exploitations at runtime

Cartografia e diplomacia: usos geopolíticos da informação toponímica (1750-1850)

O artigo explora dimensões geopolíticas da toponímia, registradas em documentos cartográficos, desde as reformas empreendidas pelo consulado pombalino em meados do século XVIII, até às primeiras décadas do século XIX, em meio ao processo de afirmação do Estado imperial pós-colonial.This paper explores the geopolitical dimensions of toponymy as registered in cartographic documents dating from the reforms pushed through by the consulate of Marquis of Pombal in the mid 18th century to the early decades of the 19th century, as the post-colonial imperial State established itself

Estimates of repeatability coefficients and the number of the optimum measure to select superior genotypes in Annona muricata L.

The aim of this study was to evaluate repeated measures over the years to estimate repeatability coefficient and the number of the optimum measure to select superior genotypes in Annona muricata L. The fruit production was evaluated over 16 years in 71 genotypes without an experimental design. The estimation of variance components and the prediction of the permanent phenotypic value were performed using REML/BLUP proceedings. The coefficient of determination, accuracy, and selective efficiency increased when measures increased. The coefficient of determination of 80% was reached beyond 8 crop seasons with high accuracy and selective efficiency. Thus, the evaluation of 8 crop seasons can be suitable to select superior genotypes in the A. muricata L. breeding program. Predicted selection gain had a high magnitude for fruit production indicating that it is possible to take a progressive genetic advance for this trait over cycle breeding

Detecting Distributed Denial of Service Attacks in Neighbour Discovery Protocol Using Machine Learning Algorithm Based on Streams Representation

© 2018, Springer International Publishing AG, part of Springer Nature. The main protocol of the Internet protocol version 6 suites is the neighbour discovery protocol, which is geared towards substitution of address resolution protocol, router discovery, and function redirection in Internet protocol version 4. Internet protocol version 6 nodes employ neighbour discovery protocol to detect linked hosts and routers in Internet protocol version 6 network without the dependence on dynamic host configuration protocol server, which has earned the neighbour discovery protocol the title of the stateless protocol. The authentication process of the neighbour discovery protocol exhibits weaknesses that make this protocol vulnerable to attacks. Denial of service attacks can be triggered by a malicious host through the introduction of spoofed addresses in neighbour discovery protocol messages. Internet version 6 protocols are not well supported by Network Intrusion Detection System as is the case with Internet Protocol version 4 protocols. Several data mining techniques have been introduced to improve the classification mechanism of Intrusion detection system. In addition, extensive researches indicated that there is no Intrusion Detection system for Internet Protocol version 6 using advanced machine-learning techniques toward distributed denial of service attacks. This paper aims to detect Distributed Denial of Service attacks of the Neighbour Discovery protocol using machine-learning techniques, due to the severity of the attacks and the importance of Neighbour Discovery protocol in Internet Protocol version 6. Decision tree algorithm and Random Forest Algorithm showed high accuracy results in comparison to the other benchmarked algorithms

Gaia Data Release 1: Testing parallaxes with local Cepheids and RR Lyrae stars

Context. Parallaxes for 331 classical Cepheids, 31 Type II Cepheids, and 364 RR Lyrae stars in common between Gaia and the Hipparcos and Tycho-2 catalogues are published in Gaia Data Release 1 (DR1) as part of the Tycho-Gaia Astrometric Solution (TGAS). Aims. In order to test these first parallax measurements of the primary standard candles of the cosmological distance ladder, which involve astrometry collected by Gaia during the initial 14 months of science operation, we compared them with literature estimates and derived new period-luminosity (PL), period-Wesenheit (PW) relations for classical and Type II Cepheids and infrared PL, PL-metallicity (PLZ), and optical luminosity-metallicity (M V -[Fe/H]) relations for the RR Lyrae stars, with zero points based on TGAS. Methods. Classical Cepheids were carefully selected in order to discard known or suspected binary systems. The final sample comprises 102 fundamental mode pulsators with periods ranging from 1.68 to 51.66 days (of which 33 with σ Ω /Ω < 0.5). The Type II Cepheids include a total of 26 W Virginis and BL Herculis stars spanning the period range from 1.16 to 30.00 days (of which only 7 with σ Ω /Ω < 0.5). The RR Lyrae stars include 200 sources with pulsation period ranging from 0.27 to 0.80 days (of which 112 with σ Ω /Ω < 0.5). The new relations were computed using multi-band (V,I,J,K s ) photometry and spectroscopic metal abundances available in the literature, and by applying three alternative approaches: (i) linear least-squares fitting of the absolute magnitudes inferred from direct transformation of the TGAS parallaxes; (ii) adopting astrometry-based luminosities; and (iii) using a Bayesian fitting approach. The last two methods work in parallax space where parallaxes are used directly, thus maintaining symmetrical errors and allowing negative parallaxes to be used. The TGAS-based PL,PW,PLZ, and M V - [Fe/H] relations are discussed by comparing the distance to the Large Magellanic Cloud provided by different types of pulsating stars and alternative fitting methods. Results. Good agreement is found from direct comparison of the parallaxes of RR Lyrae stars for which both TGAS and HST measurements are available. Similarly, very good agreement is found between the TGAS values and the parallaxes inferred from the absolute magnitudes of Cepheids and RR Lyrae stars analysed with the Baade-Wesselink method. TGAS values also compare favourably with the parallaxes inferred by theoretical model fitting of the multi-band light curves for two of the three classical Cepheids and one RR Lyrae star, which were analysed with this technique in our samples. The K-band PL relations show the significant improvement of the TGAS parallaxes for Cepheids and RR Lyrae stars with respect to the Hipparcos measurements. This is particularly true for the RR Lyrae stars for which improvement in quality and statistics is impressive. Conclusions. TGAS parallaxes bring a significant added value to the previous Hipparcos estimates. The relations presented in this paper represent the first Gaia-calibrated relations and form a work-in-progress milestone report in the wait for Gaia-only parallaxes of which a first solution will become available with Gaia Data Release 2 (DR2) in 2018. © ESO, 2017

Using death to one's advantage: HIV modulation of apoptosis

Infection by human immunodeficiency virus (HIV) is associated with an early immune dysfunction and progressive destruction of CD4+ T lymphocytes. This progressive disappearance of T cells leads to a lack of immune control of HIV replication and to the development of immune deficiency resulting in the increased occurrence of opportunistic infections associated with acquired immune deficiency syndrome (AIDS). The HIV-induced, premature destruction of lymphocytes is associated with the continuous production of HIV viral proteins that modulate apoptotic pathways. The viral proteins, such as Tat, Env, and Nef, are associated with chronic immune activation and the continuous induction of apoptotic factors. Viral protein expression predisposes lymphocytes, particularly CD4+ T cells, CD8+ T cells, and antigen-presenting cells, to evolve into effectors of apoptosis and as a result, to lead to the destruction of healthy, non-infected T cells. Tat and Nef, along with Vpu, can also protect HIV-infected cells from apoptosis by increasing anti-apoptotic proteins and down- regulating cell surface receptors recognized by immune system cells. This review will discuss the validity of the apoptosis hypothesis in HIV disease and the potential mechanism(s) that HIV proteins perform in the progressive T cell depletion observed in AIDS pathogenesis. Originally published Leukemia, Vol. 15, No. 3, Mar 200