MiRNA as a Potential Target for Multiple Myeloma Therapy-Current Knowledge and Perspectives.

Multiple myeloma (MM) is the second most common hematological malignancy. Despite the huge therapeutic progress thanks to the introduction of novel therapies, MM remains an incurable disease. Extensive research is currently ongoing to find new options. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression at a post-transcriptional level. Aberrant expression of miRNAs in MM is common. Depending on their role in MM development, miRNAs have been reported as oncogenes and tumor suppressors. It was demonstrated that specific miRNA alterations using miRNA mimics or antagomirs can normalize the gene regulatory network and signaling pathways in the microenvironment and MM cells. These properties make miRNAs attractive targets in anti-myeloma therapy. However, only a few miRNA-based drugs have been entered into clinical trials. In this review, we discuss the role of the miRNAs in the pathogenesis of MM, their current status in preclinical/clinical trials, and the mechanisms by which miRNAs can theoretically achieve therapeutic benefit in MM treatment.

Therapeutic Potential of Innate Lymphoid Cells for Multiple Myeloma Therapy.

Innate lymphoid cells (ILCs) are a recently identified family of lymphocyte-like cells lacking a specific antigen receptor. They are part of the innate immune system. They play a key role in tissue homeostasis and also control inflammatory and neoplastic processes. In response to environmental stimuli, ILCs change their phenotype and functions, and influence the activity of other cells in the microenvironment. ILC dysfunction can lead to a wide variety of diseases, including cancer. ILC can be divided into three subgroups: ILC Group 1, comprising NK cells and ILC1; Group 2, including ILC2 alone; and Group 3, containing Lymphoid Tissue inducers (LTi) and ILC3 cells. While Group 1 ILCs mainly exert antitumour activity, Group 2 and Group 3 ILCs are protumorigenic in nature. A growing body of preclinical and clinical data support the role of ILCs in the pathogenesis of multiple myeloma (MM). Therefore, targeting ILCs may be of clinical benefit. In this manuscript, we review the available data on the role of ILCs in MM immunology and therapy.

Assessment of impact of daily huddles and visual displays on medication delivery timeliness in a large academic medical center.

PURPOSE: To evaluate the impact of pharmacy team huddles and near real-time performance dashboards on the punctuality of medication delivery departures from the adult inpatient pharmacy of a multihospital medical center. METHODS: Baseline delivery punctuality was established during a 2-week unannounced preintervention period, followed by the implementation of daily huddles focused on delivery timeliness along with visual displays of delivery performance metrics. The 5- to 15-minute huddles included pharmacy technicians, pharmacists, and managers. Printed visual displays that tracked hour-by-hour timeliness over the prior 24 hours were prominently displayed in the pharmacy. The primary outcome was the overall change in the percentage of punctual medication delivery departures (ie, deliveries leaving the pharmacy at the scheduled time) during the 2 weeks after implementation of huddles and visual displays (the postintervention period). Punctuality was assessed at both the day and shift levels using generalized estimating equations in a piecewise regression model. A multivariable model was constructed using a forward stepwise selection process to assess the potential impacts of workload drivers and staffing levels on medication delivery punctuality. RESULTS: During the pre- and postintervention periods, the punctuality of a total of 1,032 deliveries was recorded. Punctuality of deliveries across all shifts increased by 37% (95% confidence interval [CI], 18%-56% [P < 0.001]), from 50% to 87%, immediately following implementation of the huddle intervention. When punctuality was assessed by individual shift, we observed statistically significant increases for the day (35% [95% CI, 13%-57%], P = 0.002), evening (34% [95% CI, 12%-56%], P = 0.003) and night (57% [95% CI, 35%-79%], P < 0.001) shifts. During the forward stepwise multivariable model-building process, order volume, message volume, and technician staffing levels were not significantly correlated with delivery punctuality at the day or shift level. CONCLUSION: Daily huddles with visual displays were successful in improving the punctuality of medication delivery departures from the pharmacy, independent of workload drivers and staffing levels.

Impact of working 48 h per week on opportunities for training and patient contact: the experience of Irish interns.

OBJECTIVE: The European Working Time Regulations (EWTR) have been criticized for its purported negative impact on the training of junior doctors. The aim of this study was to examine the amount of time interns spent engaging in various work activities. DESIGN: An online time-use diary was used to collect data from interns. SETTING: Two teaching hospitals in the Republic of Ireland. PARTICIPANTS: A total of 45 interns logged at least one 24-h period. The logs were obtained from 67 shifts from a surgical rotation and 83 shifts from a medical rotation. MAIN OUTCOME MEASURES: The amount of time interns spent engaging in direct patient care, indirect patient care, educational activities and personal activities. RESULTS: On day shift, medical interns spent a significantly smaller proportion of the shift on direct care (159/613 min, 25.9% versus 214/636 min, 33.6%) and a greater proportion on education (195/613 min, 31.8% versus 139/636 min, 21.9%) than surgical interns. On extended days, medical interns spent a significantly larger proportion of the shift on education than surgical interns (243/814 min, 29.9% versus 126/804, 15.7% min). On night shift, medical interns spent a significantly greater proportion of the shift on direct care (590/720 min, 81.9% versus 346/727 min, 47.6%) and education (33/720 min, 4.6% versus 6/727 min, 0.8%) than surgical interns. CONCLUSIONS: The interns in the study reported spending more time on direct patient care and educational activities, and less time on indirect patient care activities than interns in other countries.

Extreme scaling of production visualization software on diverse architectures.

This article presents the results of experiments studying how the pure-parallelism paradigm scales to massive data sets, including 16,000 or more cores on trillion-cell meshes, the largest data sets published to date in the visualization literature. The findings on scaling characteristics and bottlenecks contribute to understanding how pure parallelism will perform in the future.

Coupling visualization and data analysis for knowledge discovery from multi-dimensional scientific data.

Knowledge discovery from large and complex scientific data is a challenging task. With the ability to measure and simulate more processes at increasingly finer spatial and temporal scales, the growing number of data dimensions and data objects presents tremendous challenges for effective data analysis and data exploration methods and tools. The combination and close integration of methods from scientific visualization, information visualization, automated data analysis, and other enabling technologies -such as efficient data management- supports knowledge discovery from multi-dimensional scientific data. This paper surveys two distinct applications in developmental biology and accelerator physics, illustrating the effectiveness of the described approach.

Visualizing temporal patterns in large multivariate data using textual pattern matching.

Extracting and visualizing temporal patterns in large scientific data is an open problem in visualization research. First, there are few proven methods to flexibly and concisely define general temporal patterns for visualization. Second, with large time-dependent data sets, as typical with today's large-scale simulations, scalable and general solutions for handling the data are still not widely available. In this work, we have developed a textual pattern matching approach for specifying and identifying general temporal patterns. Besides defining the formalism of the language, we also provide a working implementation with sufficient efficiency and scalability to handle large data sets. Using recent large-scale simulation data from multiple application domains, we demonstrate that our visualization approach is one of the first to empower a concept driven exploration of large-scale time-varying multivariate data.

Chromium Renderserver: scalable and open remote rendering infrastructure.

Chromium Renderserver (CRRS) is software infrastructure that provides the ability for one or more users to run and view image output from unmodified, interactive OpenGL and X11 applications on a remote, parallel computational platform equipped with graphics hardware accelerators via industry-standard Layer 7 network protocols and client viewers. The new contributions of this work include a solution to the problem of synchronizing X11 and OpenGL command streams, remote delivery of parallel hardware accelerated rendering, and a performance analysis of several different optimizations that are generally applicable to a variety of rendering architectures. CRRS is fully operational, Open Source software. imagery and sending it to a remote viewer.