Low-dose salinomycin induces anti-leukemic responses in AML and MLL

Development of anti-cancer drugs towards clinical application is costly and inefficient. Large screens of drugs, efficacious for non-cancer disease, are currently being used to identify candidates for repurposing based on their anti-cancer properties. Here, we show that low-dose salinomycin, a coccidiostat ionophore previously identified in a breast cancer screen, has anti-leukemic efficacy. AML and MLLr cell lines, primary cells and patient samples were sensitive to submicromolar salinomycin. Most strikingly, colony formation of normal hematopoietic cells was unaffected by salinomycin, demonstrating a lack of hemotoxicity at the effective concentrations. Furthermore, salinomycin treatment of primary cells resulted in loss of leukemia repopulation ability following transplantation, as demonstrated by extended recipient survival compared to controls. Bioinformatic analysis of a 17-gene signature identified and validated in primary MLLr cells, uncovered immunomodulatory pathways, hubs and protein interactions as potential transducers of low dose salinomycin treatment. Additionally, increased protein expression of p62/Sqstm1, encoded for by one of the 17 signature genes, demonstrates a role for salinomycin in aggresome/vesicle formation indicative of an autophagic response.
Together, the data support the efficacy of salinomycin as an anti-leukemic at non-hemotoxic concentrations. Further investigation alone or in combination with other therapies is warranted for future clinical trial.

CAUSAL INFERENCE WITH A CONTINUOUS TREATMENT AND OUTCOME: ALTERNATIVE ESTIMATORS FOR PARAMETRIC DOSE-RESPONSE FUNCTIONS WITH APPLICATIONS.

Causal inference with a continuous treatment is a relatively under-explored problem. In this dissertation, we adopt the potential outcomes framework. Potential outcomes are responses that would be seen for a unit under all possible treatments. In an observational study where the treatment is continuous, the potential outcomes are an uncountably infinite set indexed by treatment dose. We parameterize this unobservable set as a linear combination of a finite number of basis functions whose coefficients vary across units. This leads to new techniques for estimating the population average dose-response function (ADRF). Some techniques require a model for the treatment assignment given covariates, some require a model for predicting the potential outcomes from covariates, and some require both. We develop these techniques using a framework of estimating functions, compare them to existing methods for continuous treatments, and simulate their performance in a population where the ADRF is linear and the models for the treatment and/or outcomes may be misspecified. We also extend the comparisons to a data set of lottery winners in Massachusetts. Next, we describe the methods and functions in the R package causaldrf using data from the National Medical Expenditure Survey (NMES) and Infant Health and Development Program (IHDP) as examples. Additionally, we analyze the National Growth and Health Study (NGHS) data set and deal with the issue of missing data. Lastly, we discuss future research goals and possible extensions.

Optimal resource allocation and budgeting in libraries

Libraries since their inception 4000 years ago have been in a process of constant change. Although, changes were in slow motion for centuries, in the last decades, academic libraries have been continuously striving to adapt their services to the ever-changing user needs of students and academic staff. In addition, e-content revolution, technological advances, and ever-shrinking budgets have obliged libraries to efficiently allocate their limited resources among collection and services. Unfortunately, this resource allocation is a complex process due to the diversity of data sources and formats required to be analyzed prior to decision-making, as well as the lack of efficient integration methods. The main purpose of this study is to develop an integrated model that supports libraries in making optimal budgeting and resource allocation decisions among their services and collection by means of a holistic analysis. To this end, a combination of several methodologies and structured approaches is conducted. Firstly, a holistic structure and the required toolset to holistically assess academic libraries are proposed to collect and organize the data from an economic point of view. A four-pronged theoretical framework is used in which the library system and collection are analyzed from the perspective of users and internal stakeholders. The first quadrant corresponds to the internal perspective of the library system that is to analyze the library performance, and costs incurred and resources consumed by library services. The second quadrant evaluates the external perspective of the library system; user’s perception about services quality is judged in this quadrant. The third quadrant analyses the external perspective of the library collection that is to evaluate the impact of the current library collection on its users. Eventually, the fourth quadrant evaluates the internal perspective of the library collection; the usage patterns followed to manipulate the library collection are analyzed. With a complete framework for data collection, these data coming from multiple sources and therefore with different formats, need to be integrated and stored in an adequate scheme for decision support. A data warehousing approach is secondly designed and implemented to integrate, process, and store the holistic-based collected data. Ultimately, strategic data stored in the data warehouse are analyzed and implemented for different purposes including the following: 1) Data visualization and reporting is proposed to allow library managers to publish library indicators in a simple and quick manner by using online reporting tools. 2) Sophisticated data analysis is recommended through the use of data mining tools; three data mining techniques are examined in this research study: regression, clustering and classification. These data mining techniques have been applied to the case study in the following manner: predicting the future investment in library development; finding clusters of users that share common interests and similar profiles, but belong to different faculties; and predicting library factors that affect student academic performance by analyzing possible correlations of library usage and academic performance. 3) Input for optimization models, early experiences of developing an optimal resource allocation model to distribute resources among the different processes of a library system are documented in this study. Specifically, the problem of allocating funds for digital collection among divisions of an academic library is addressed. An optimization model for the problem is defined with the objective of maximizing the usage of the digital collection over-all library divisions subject to a single collection budget. By proposing this holistic approach, the research study contributes to knowledge by providing an integrated solution to assist library managers to make economic decisions based on an “as realistic as possible” perspective of the library situation.

Therapeutic effects of ciprofloxacin/bushenhuazhuo combination on chronic prostatitis

Purpose: To evaluate the clinical effect of bushenhuazhuo (a Chinese traditional medicine) in combination with ciprofloxacin (an orthodox medicine) in chronic prostatitis (CP) therapy. Methods: A total of 160 patients who suffered from CP and received treatment in the People’s Hospital of Zhengzhou between April 2012 and June 2014 were selected and divided randomly into treatment and control groups, with 80 patients in each group. Control group was given 0.25 g ciprofloxacin hydrochloride tablets twice a day for 4 weeks. In addition to ciprofloxacin administration, patients in the treatment group also received a dose of bushenhuazhuo preparation twice daily for 4 weeks. Clinical outcomes, quality of life as well as lecithin body and white blood cell (WBC) count in expressed prostatic secretions (EPS-WBC) were evaluated. Results: Cure rates in the treatment and control groups were 90 and 72.50 %, respectively; this difference was significant (p < 0.05). Scores for National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), WBC, and lecithin bodies in the treatment group (8.20 ± 2.20 points, 4.50 ± 1.20 points, and 28.10 ± 2.10 points, respectively) were higher (p < 0.05) than for the control group (12.20 ± 2.20, 6.30 ± 2.20, and 23.30 ± 2.90 points, respectively). The levels of interferon (IFN)-γ and tumour necrosis factor (TNF)-α in the treatment group (26.20 ± 3.30 and 33.80 ± 5.40 mg/L, respectively) were lower than those in the control group (37.70 ± 3.90 and 48.40 ± 3.70 mg/L, respectively), whereas the level of interleukin (IL)-10 in the treatment group (292.60 ± 23.70 mg/L) was higher (p < 0.05) than that in control group (235.80 ± 25.90 mg/L). Conclusion: Ciprofloxacin combined with the Chinese traditional medicine, bushenhuazhuo preparation, demonstrates a marked therapeutic effect in CP. Its mechanism of action may be related to decreased levels of IFN-γ and TNF-α and increased IL-10.

Combination methods for identifying influential nodes in networks

Identifying influential nodes is of theoretical significance in many domains. Although lots of methods have been proposed to solve this problem, their evaluations are under single-source attack in scale-free networks. Meanwhile, some researches have speculated that the combinations of some methods may achieve more optimal results. In order to evaluate this speculation and design a universal strategy suitable for different types of networks under the consideration of multi-source attacks, this paper proposes an attribute fusion method with two independent strategies to reveal the correlation of existing ranking methods and indicators. One is based on feature union (FU) and the other is based on feature ranking (FR). Two different propagation models in the fields of recommendation system and network immunization are used to simulate the efficiency of our proposed method. Experimental results show that our method can enlarge information spreading and restrain virus propagation in the application of recommendation system and network immunization in different types of networks under the condition of multi-source attacks.

Optimal sensing requirement for slippage prevention in robotic grasping

This paper presents a new theoretical development and modelling related to the requirement of the minimum number of sensors necessary for slippage prevention in robotic grasping. A fundamental experimental investigation has been conducted to support the newly developed postulate. A series of basic experiments proved that it is possible to evaluate the contributions of various sensors to slippage prevention and control in robotic grasping. The use of three discrete physical sensors, one for each of the three sensing functions (normal, tangential and slippage), has been proven to be the most reliable combination for slippage prevention in robotic grasping. It was also proven that the best performance from a two-sensor combination can be achieved when normal grasp force and tangential force are both monitored in the grasping process.

A combination of omega-3 fatty acids, folic acid and B-group vitamins is superior at lowering homocysteine than omega-3 alone: a meta-analysis

The aim of the study was to assess whether omega-3 polyunsaturated fatty acid supplementation alone or in combination with folic acid and B-group vitamins is effective in lowering homocysteine. The Medline Ovid, Embase and Cochrane databases were searched for randomized-controlled trial studies that intervened with omega-3 supplementation (with or without folic acid) and measured changes in homocysteine concentration. Studies were pooled using a random effects model for meta-analysis. Three different models were analyzed: all trials combined, omega-3 polyunsaturated fatty acid trials, and omega-3 polyunsaturated fatty acids with folic acid and B-group vitamin trials. Nineteen studies were included, consisting of 3267 participants completing 21 trials. Studies were heterogeneous; varying by dose, duration and participant health conditions. Across all trials, omega-3 supplementation was effective in lowering homocysteine by an average of 1.18μmol/L (95%CI: (-1.89, -0.48), P=.001). The average homocysteine-lowering effect was greater when omega-3 supplementation was combined with folic acid and B-group vitamins (-1.37μmol/L, 95%CI: (-2.38, -0.36), P<.01) compared to omega-3 supplementation alone (-1.09μmol/L 95%CI: (-2.04, -0.13), P=.03). Omega-3 polyunsaturated fatty acid supplementation was associated with a modest reduction in homocysteine. For the purposes of reducing homocysteine, a combination of omega-3s (0.2-6g/day), folic acid (150 - 2500μg/day) and vitamins B6 and B12 may be more effective than omega-3 supplementation alone.

Cost optimal resource provisioning for live video forwarding across video data centers

Live video forwarding for IP cameras has become a popular service in video data centers. In the forwarding service, requests of end users from different regions arrive in real-time to gain live video streams of IP cameras from inter-connected video data centers. A fundamental scheduling problem is how to assign resources with the global optimal resource cost and forwarding delay to forward live video streams. We introduce the resource provisioning cost as the combination of media server cost, connection bandwidth cost, and forwarding delay cost. In this paper, a multi-objective resource provisioning (MORP) approach is proposed to deal with the online inter-datacenter resource provisioning problem. The approach aims at minimizing the resource provisioning cost during live video forwarding. It adaptively allocates media servers in appropriate video data centers and connects the chosen media servers together to provide system scalability and connectivity. Different from previous works, MORP takes both resource capacity and diversity (e.g. location and price) into consideration during live video forwarding. Finally, the experimental results show that MORP approach not only cuts the resource provisioning cost of 3% to 10% comparing to the bench mark approach, but also shortens the resource provisioning delay.

Tratamiento del rechazo mediado por anticuerpos en pacientes trasplantados renales revisión sistemática

Antecedentes: El trasplante renal es la mejor alternativa terapéutica para la enfermedad renal crónica terminal. Los medicamentos inmunosupresores previenen el rechazo. El rechazo mediado por anticuerpos es frecuente y disminuye la función y duración del injerto. Objetivo: Evaluar sistemáticamente la evidencia disponible relacionada con la eficacia y seguridad del tratamiento para el rechazo mediado por anticuerpos en pacientes trasplantados renales. Metodologia: Revisión sistemática en bases de datos MEDLINE, EMBASE, Scopus y Biblioteca virtual de la salud. Literatura gris google scholar, google academico, www.clinicaltrialsregister.eu, and https://clinicaltrials.gov/. Búsqueda manual referencias artículos pre-seleccionados así como de revisiones previamente publicadas. Se siguieron las recomendacioes guia PRISMA para la identificacion de artículos potenciales, tamizaje y selección teniendo en cuenta los criterios de inclusion. Extracción datos de acuerdo a las variables, revisión calidad de los artículos elegidos utilizando evaluación riesgo de segos de Cochrane. Resultados: Se seleccionaron 9 ensayos clínicos publicados entre 1980 y 2016, incluyeron 222 pacientes (113 brazo de intervención y 109 en el control), seguimiento promedio 16 meses. Intervenciones evaluadas plasmaféresis, inmunoadsorción y rituximab. Hubo una amplia heterogeneidad en la definición de criterios de inclusión, criterios diagnósticos de rechazo y medidas de evaluación de eficacia de las intervenciones. Tres estudios encontraron diferencias estadísticamente significativas entre los grupos de tratamiento. Conclusiones: La evidencia sobre la eficacia de los tratamientos del rechazo mediado por anticuerpos en injertos renales es de baja calidad. Son necesarios ensayos clínicos controlados para poder definir el tratamiento óptimo de estos pacientes.

Incidencia de síndrome de abstinencia secundario a opioides y/o benzodiacepinas en dos unidades de cuidados intensivos pediátricos

• Introducción: El síndrome de abstinencia (SA) es el conjunto de síntomas y signos que se producen al suspender bruscamente la administración de un fármaco una vez se haya establecido dependencia física. • Objetivos: Caracterizar los pacientes que presentan SA secundario a opiodes (OP) y/o benzodiacepinas(BZ) durante la hospitalización en las unidades de cuidados intensivos pediátricos de la Clínica Infantil Colsubsidio (CIC) y Hospital del Niño de Panamá (HDN) del 1 de abril al 30 de septiembre del 2016. • Materiales y métodos: se realizó un estudio descriptivo, longitudinal, prospectivo. Incluimos 189 pacientes en la CIC y 144 pacientes en el HDN. Se utilizó la escala SOPHIA para el diagnóstico de SA, las escalas COMFORT para evaluar la sedación en pacientes ventilados no relajados y la escala FLACC para evaluar la analgesia. Se utilizó software StataV12® para el análisis estadístico. • Resultados: se reportó una incidencia global de SA de 6.1/100 días personas. La incidencia acumulada de SA fue de 56.08% y 29.86% para la CIC y el HDN respectivamente. En la CIC el 69.81% de los pacientes que requirieron infusión de OP y BZ desarrollaron SA. Se reportó una dosis acumulada de fentanyl de 530.34 ± 276.49 mcg/kg. Con respecto al HDN, de los pacientes que recibieron opioides y benzodiacepinas el 53.49 % desarrollaron SA. • Conclusión: El SA secundario a opioides y/o benzodiacepinas es frecuente en nuestras unidades con una incidencia variable, es mayor la presentación del SA al usar ambos fármacos, mayores dosis acumuladas y más días de infusión continua.