Ofatumumab and high-dose methylprednisolone for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia.

Ofatumumab is a humanized anti-CD20 monoclonal antibody that has been approved by the FDA for the treatment of patients with chronic lymphocytic leukemia. We conducted a phase II single-arm study at a single center. Patients received ofatumumab (300 mg then 1000 mg weekly for 12 weeks) and methylprednisolone (1000 mg/m(2) for 3 days of each 28-day cycle). Twenty-one patients enrolled, including 29% with unfavorable cytogenetics (del17p or del11q). Ninety percent of patients received the full course without dose reductions or delays. The overall response rate was 81% (17/21) with 5% complete response, 10% nodular partial response, 67% partial response, 14% stable disease and 5% progressive disease. After a median follow-up of 31 months, the median progression-free survival was 9.9 months and the median time to next treatment was 12.1 months. The median overall survival has not yet been reached. The combination of high-dose methylprednisolone and ofatumumab is an effective and tolerable treatment regimen. This regimen may be useful for patients who are unable to tolerate more aggressive therapies, or have not responded to other treatments

Rituximab in combination with high-dose methylprednisolone for the treatment of chronic lymphocytic leukemia.

We observed that high-dose methylprednisolone (HDMP) and rituximab was well tolerated and had promising activity when used in combination to treat patients with fludarabine-refractory chronic lymphocytic leukemia (CLL). This prompted us to evaluate the use of these agents in frontline therapy. A total of 28 patients with a median age of 65 years enrolled in this study. Patients received HDMP at 1 g/m(2) each day for 3 days during each of the three 4-week cycles together with rituximab and prophylactic antimicrobial therapy. The treatment was well tolerated with few adverse events of grade III or higher. The overall response rate was 96% (N=27). Nine patients (32%) achieved a complete remission (CR), two of which were without detectable minimal residual disease (MRD). Six patients with MRD received consolidation with alemtuzumab; five of these patients achieved an MRD-negative CR. With over 3 years of follow-up median progression-free survival was 30.3 months with only 39% of patients requiring additional therapy, and an overall survival was 96%. This study demonstrates that HDMP and rituximab is an effective nonmyelosuppressive treatment combination for patients with CLL that warrants consideration particularly for patients with limited myeloid reserve that might not tolerate standard treatment regimens

Seroprevalence of Toxoplasmosis in Blood Donors: An Investigation from the Endemicity. Non-systematic Review

Toxoplasma gondii is an intracellular protozoan that causes toxoplasmosis, the most common parasitic disease in the world, which infects humans and animals. It is transmitted through cat feces through the process of excretion and ingestion of oocysts. Humans become infected by eating improperly washed vegetables, raw or undercooked meat, contaminated water, the soil or area where the cat defecates, or by transfusing infected blood. The study aims to identify, through scientific evidence, the seroprevalence of T. gondii in blood donors, considering its global endemicity. A non-systematic documentary review was used for searching articles worldwide on the topic of T. gondii seroprevalence in blood donors, in different databases such as SciELO, Google Academics, etc. A total of 27 articles that had the required information; grouping the seroprevalence results by region, obtained positive IgG and IgG + IgM. Calculating the prevalence, it was identified in Asia at 7.8%, America 32.8%, Africa 40.7%, Oceania 34%, and Europe 38.1%. In conclusion, it is convenient to carry out this type of study in each country to verify the prevalence and, in addition, to determine the incidence of infection in blood donors to calculate the risk of transmission. Keywords: Toxoplasma, seroepidemiologic studies, antibodies, immunoglobulin G, immunoglobulin M, blood donors. Resumen Introducción: Toxoplasma gondii en un protozoo intracelular causante de la toxoplasmosis, la enfermedad parasitaria más frecuente del mundo la cual infecta a humanos y animales, se trasmite por medio de las heces de los gatos mediante el proceso de excreción e ingestión de los ooquistes. Los humanos se infectan al ingerir vegetales mal lavados, carne cruda o poco cocida, agua contaminada, el suelo o área donde defeca el gato, o al transfundir sangre infectada. Objetivo: identificar mediante evidencias científicas la seroprevalencia de T. gondii en donantes de sangre, considerando su endemicidad global. Metodología: se empleó una revisión no sistemática, documental realizando la búsqueda de artículos a nivel mundial del tema seroprevalencia de T. gondii en donantes de sangre, en diferentes bases como SciELO, Google Academics, etc. Resultados: un total de 27 artículos que contaron con la información requerida; agrupando los resultados de seroprevalencia por región, anticuerpos positivos IgG e IgG + IgM. Calculando la prevalencia se identificó, en Asia 7,8%; América 32,8%; África 40,7%; Oceanía 34% y Europa 38,1%. Conclusión: es conveniente realizar este tipo de estudio en cada país para comprobar la prevalencia y, además, determinar la incidencia de la infección en donantes de sangre para calcular el riesgo de transmisión. Palabras Clave: Toxoplasma, estudios seroepidemiológicos, anticuerpos, inmunoglobulina G, inmunoglobulina M, donantes de sangre

A discrete MMAP for analysing the behaviour of a multi-state complex dynamic system subject to multiple events.

A complex multi-state system subject to different types of failures, repairable and/or nonrepairable, external shocks and preventive maintenance is modelled by considering a discrete Markovian arrival process with marked arrivals (D-MMAP). The internal performance of the system is composed of several degradation states partitioned into minor and major damage states according to the risk of failure. Random external events can produce failures throughout the system. If an external shock occurs, there may be an aggravation of the internal degradation, cumulative external damage or extreme external failure. The internal performance and the cumulative external damage are observed by random inspection. If major degradation is observed, the unit goes to the repair facility for preventive maintenance. If a repairable failure occurs then the system goes to corrective repair with different time distributions depending on the failure state. Time distributions for corrective repair and preventive maintenance depend on the failure state. Rewards and costs depending on the state at which the device failed or was inspected are introduced. The system is modelled and several measures of interest are built into transient and stationary regimes. A preventive maintenance policy is shown to determine the effectiveness of preventive maintenance and the optimum state of internal and cumulative external damage at which preventive maintenance should be taken into account. A numerical example is presented, revealing the efficacy of the model. Correlations between the numbers of different events over time and in non-overlapping intervals are calculated. The results are expressed in algorithmic-matrix form and are implemented computationally with Matlab.Junta de Andalucía, Spain, under the grant FQM307Ministerio de Economía y Competitividad, España, MTM2017-88708-PEuropean Regional Development Fund (ERDF

Systemic Design for Food Self-Sufficiency in Urban Areas

This article adopts a systemic approach to address the problem of the operationalization of relationships between actors conducive to food self-sufficiency in urban areas. Through the use of Social Network Analysis (SNA), the literature on urban agriculture was analyzed, detecting eight key trends and topic areas. This information was used to design a generic recursive organizational structure with the identification of the key roles and functions for management and governance in the multi-level and multi-stakeholder relationships of a sustainable urban self-sufficient food production system, inspired by the principles of complexity management and organizational cybernetics. Methodologically, this is the first application that combines the exploratory capability of SNA and the recursive structure of the Viable System Model (VSM) to propose applicable organizational structures in any urban area, suggesting a new route for the study and application of systemic thinking in the development of urban agriculture schemes. However, due to the conceptual nature of this work, this study opens a discussion on how we can rethink interactions to seek continuous adaptation in food self-sufficiency, provide tools that foster inclusion, and adapt to every context to support the relevant actors and academics in urban agriculture.</jats:p

Intestinal Serotonin Transporter Inhibition by Toll-Like Receptor 2 Activation. A Feedback Modulation

This is the final version of the article. Available from Public Library of Science via the DOI in this record.TLR2 is a microbiota recognition receptor that has been described to contribute to intestinal homeostasis and to ameliorate inflammatory intestinal injury. In this context, serotonin (5-HT) has shown to be an essential intestinal physiological neuromodulator that is also involved in intestinal inflammatory diseases. Since the interaction between TLR2 activation and the intestinal serotoninergic system remains non-investigated, our main aim was to analyze the effect of TLR2 on intestinal serotonin transporter (SERT) activity and expression and the intracellular pathways involved. Caco-2/TC7 cells were used to analyze SERT and TLR2 molecular expression and SERT activity by measuring 5-HT uptake. The results showed that apical TLR2 activation inhibits SERT activity in Caco-2/TC7 cells mainly by reducing SERT protein level either in the plasma membrane, after short-term TLR2 activation or in both the plasma membrane and cell lysate, after long-term activation. cAMP/PKA pathway appears to mediate short-term inhibitory effect of TLR2 on SERT; however, p38 MAPK pathway has been shown to be involved in both short- and long-term TLR2 effect. Reciprocally, 5-HT long-term treatment yielded TLR2 down regulation in Caco-2/TC7 cells. Finally, results from in vivo showed an augmented intestinal SERT expression in mice Tlr2-/-, thus confirming our inhibitory effect of TLR2 on intestinal SERT in vitro. The present work infers that TLR2 may act in intestinal pathophysiology, not only by its inherent innate immune role, but also by regulating the intestinal serotoninergic system.This work was funded by grants from the Spanish Ministry of Science and Innovation and the European Regional Development Fund (ERDF/FEDER) (BFU2010-18971), Zaragoza University (UZ2014-BIO-03), European Social Found (ESF) and the Aragon Regional Government (B61) and the Foundation for the Study of Inflammatory Bowel Diseases in Aragón (ARAINF 012/2008). ARAID Foundation supported J.P. (SAF2014-54763-C2-1-R) and E. Layunta is a PhD student fellow from Aragon Regional Government (B022/13). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Categorical Dimensions of Human Odor Descriptor Space Revealed by Non-Negative Matrix Factorization

In contrast to most other sensory modalities, the basic perceptual dimensions of olfaction remain unclear. Here, we use non-negative matrix factorization (NMF) – a dimensionality reduction technique – to uncover structure in a panel of odor profiles, with each odor defined as a point in multi-dimensional descriptor space. The properties of NMF are favorable for the analysis of such lexical and perceptual data, and lead to a high-dimensional account of odor space. We further provide evidence that odor dimensions apply categorically. That is, odor space is not occupied homogenously, but rather in a discrete and intrinsically clustered manner. We discuss the potential implications of these results for the neural coding of odors, as well as for developing classifiers on larger datasets that may be useful for predicting perceptual qualities from chemical structures

Rapid ascent of rhyolitic magma at Chaitén volcano, Chile

International audienceAlthough rhyolite magma has fuelled some of the Earth's largest explosive volcanic eruptions, our understanding of these events is incomplete due to the previous lack of direct observation of these eruptions. On 1 May 2008, Chaitén volcano in Chile erupted rhyolite magma unexpectedly and explosively. Here, petrological and experimental data are presented that indicate that the hydrous rhyolite magma at Chaitén ascended very rapidly from storage depth to near-surface, with velocities of the order of one metre per second

Absence of a Spin Liquid Phase in the Hubbard Model on the Honeycomb Lattice

A spin liquid is a novel quantum state of matter with no conventional order parameter where a finite charge gap exists even though the band theory would predict metallic behavior. Finding a stable spin liquid in two or higher spatial dimensions is one of the most challenging and debated issues in condensed matter physics. Very recently, it has been reported that a model of graphene, i.e., the Hubbard model on the honeycomb lattice, can show a spin liquid ground state in a wide region of the phase diagram, between a semi-metal (SM) and an antiferromagnetic insulator (AFMI). Here, by performing numerically exact quantum Monte Carlo simulations, we extend the previous study to much larger clusters (containing up to 2592 sites), and find, if any, a very weak evidence of this spin liquid region. Instead, our calculations strongly indicate a direct and continuous quantum phase transition between SM and AFMI.Comment: 15 pages with 7 figures and 9 tables including supplementary information, accepted for publication in Scientific Report

Lessons from building an automated pre-departure sequencer for airports

Commercial airports are under increasing pressure to comply with the Eurocontrol collaborative decision making (CDM) initiative, to ensure that information is passed between stakeholders, integrate automated decision support or make predictions. These systems can also aid effective operations beyond the airport by communicating scheduling decisions to other relevant parties, such as Eurocontrol, for passing on to downstream airports and enabling overall airspace improvements. One of the major CDM components is aimed at producing the target take-off times and target startup-approval times, i.e. scheduling when the aircraft should push back from the gates and start their engines and when they will take off. For medium-sized airports, a common choice for this is a “pre-departure sequencer” (PDS). In this paper, we describe the design and requirements challenges which arose during our development of a PDS system for medium sized international airports. Firstly, the scheduling problem is highly dynamic and event driven. Secondly, it is important to end-users that the system be predictable and, as far as possible, transparent in its operation, with decisions that can be explained. Thirdly, users can override decisions, and this information has to be taken into account. Finally, it is important that the system is as fair as possible for all users of the airport, and the interpretation of this is considered here. Together, these factors have influenced the design of the PDS system which has been built to work within an existing large system which is being used at many airport