General Research Applications Research Articles

Mining Archive.org’s Twitter Stream Grab for Pharmacovigilance Research Gold

In the last few years, Twitter has become an important resource for the identification of Adverse Drug Reactions (ADRs), monitoring flu trends, and other pharmacovigilance and general research applications. Most researchers spend their time crawling Twitter, buying expensive pre-mined datasets, or tediously and slowly building datasets using the limited Twitter API. However, there are a large number of datasets that are publicly available to researchers that are underutilized or unused. In this work, we demonstrate how we mined over 9.4 billion Tweets from archive.org’s Twitter stream grab using a drug-term dictionary and plenty of computing power. Knowing that not everything that shines is gold, we used pre-existing drug-related datasets to build machine learning models to filter our findings for relevance. In this work, we present our methodology and the 3,346,758 identified tweets for public use in future research.

Pulsed Power as a Science: Predictive Simulations for Beams, Z-Pinches, and Other Applications

This article is based on my plenary presentation that was associated with my Peter Haas Award, where I overview my 40 years of research and the people with whom I have had the pleasure of working, both domestically and internationally. In 1978, Sandia’s electron beam fusion program emerged from a weapons simulator community that was machine oriented and relied on design principles and J. Charlie Martin (JCM) criteria. The simulation tools were primarily used retrospectively. Fusions’ extraordinary requirements stimulated tremendous innovation in pulsed power, beams, pinches, and simulation tools. I started by developing ion beam deposition and transport models that were integrated into radiation-hydrodynamics codes; validated by experiments on Gamble II and Proto I; and helped initiate Sandia’s light-ion-beam fusion program. Strategic Defense Initiative (SDI) program research led to the development of the Integrated Tiger Series (ITS) suite of electron–photon Monte Carlo codes (1985). A research on Particle Beam Fusion Accelerator I (PBFA-I) and PBFA-II on generating, transporting, and focusing ion beams required developing transport, diagnostic simulation, and analysis tools, which were used in focusing protons to 5 TW/cm2 (1991) and lithium beams to 2 TW/cm2 and heating hohlraums to 65 eV (1996). They also helped identify anode plasma formation by electron heating as the source of diode impedance collapse leading to efforts to include electron–electrode interaction models into particle-in-cell (PIC) codes and initiating hybrid fluid-PIC development (IPROP, LSP). Electrode physics remains a power flow grand challenge for high-yield fusion. In 1999, I led rad-magnetohydrodynamic (MHD) development [arbitrary-Lagrangian–Eulerian general research applications high-energy-density physics (ALEGRA-HEDP)] and oversaw equation of state (EOS) and conductivity model development using quantum molecular dynamics/density function theory (QMD/DFT), resulting in predictive capabilities for dynamic material experiments. Improved z-pinch dynamic hohlraum modeling and experiments resulted in thermonuclear neutrons (2004). 3-D wire array dynamics were modeled and understood. We developed advanced radiographic sources and built a linear transformer driver (LTD) test bed. At the Naval Research Laboratory (NRL), I have overseen advances in modeling and experiments in beams, pinches, pulsed power, and their applications (2009-). My goal throughout has been to develop and validate predictive simulation tools, making pulsed power a Science.

Molecular phenotyping of laboratory mouse strains using 500 multiple reaction monitoring mass spectrometry plasma assays

Mouse is the predominant experimental model for the study of human disease due, in part, to phylogenetic relationship, ease of breeding, and the availability of molecular tools for genetic manipulation. Advances in genome-editing methodologies, such as CRISPR-Cas9, enable the rapid production of new transgenic mouse strains, necessitating complementary high-throughput and systematic phenotyping technologies. In contrast to traditional protein phenotyping techniques, multiple reaction monitoring (MRM) mass spectrometry can be highly multiplexed without forgoing specificity or quantitative precision. Here we present MRM assays for the quantitation of 500 proteins and subsequently determine reference concentration values for plasma proteins across five laboratory mouse strains that are typically used in biomedical research, revealing inter-strain and intra-strain phenotypic differences. These 500 MRM assays will have a broad range of research applications including high-throughput phenotypic validation of novel transgenic mice, identification of candidate biomarkers, and general research applications requiring multiplexed and precise protein quantification.

What changes are there in decisions by the Wits Human Research Ethics Committee (Medical) and in process errors by research applicants between 2003 and 2015?

Objective. A retrospective examination of numbers of applications, decision rates, and process errors in 2015 was done for comparison with earlier studies to understand current ethics secretariat workload. Methods . In December 2015 information from committee minutes of all the meetings ( N =11) in 2015 (January - November) was collected to quantify change in application numbers and process errors. Statistical analysis used SAS for Windows (version 9.4). Statistical significance was set at p <0.05. Results. There were 809 new general research applications considered in 2015. Monthly approvals at first evaluation ranged from 4 to 30% with an overall approval rate of 16%. Minor revision was required in 72%, major revision in 11% and 1% of applications were not approved. The χ2 test for trend for initial approval showed a statistically significant decrease across the study periods ( p <0.0001). However, the χ2 test for trend for pending responses from applicants was also statistically significant (χ2=29.64). Informed consent and missing information process errors were the most frequent. There were statistically significant increases in lapses of confidentiality methods ( p <0.0001) and discrepancies on application forms ( p <0.005). Conclusion . Applications to the Wits Human Research Ethics Committee (Medical) (HREC (M)) for ethics clearance almost doubled between 2003 and 2015 while approvals at first evaluation approximately halved. This has increased the workload on the HREC (M) secretariat. Process error rates are similar to those in an earlier study except that confidentiality and discrepancies have shown a statistically significant increase. Given limitation on the number of secretariat staff in the current stringent financial circumstances of South African universities, applicants need to improve the quality of their applications to increase approval at first review and reduce secretariat workload

Applications and secretariat workload at the University of the Witwatersrand Human Research Ethics Committee (Medical) 2002 - 2011: A case study

Objective: To examine trends in the numbers of new applications for ethics clearance of health research and associated research ethics committee secretariat activity. Methods: Data were obtained from research ethics committee secretariat databases with ethics approval. Results: General research applications increased from 440 in 2002 to 685 in 2011, all handled by one full-time staff member. This load is expected to increase by 250 per year for 2012, 2013 and 2014 before reaching a plateau. This new applications load per year is based on registered clinical postgraduates at the University of the Witwatersrand in a 4-year specialisation who must comply with the new Health Professions Council of South Africa requirement for completion of Master’s level research in order to register as a clinical specialist. Sponsored clinical trials have remained and should remain at approximately 100 per year but require three staff members to attend to this workload. Conclusion: The increased workload is a serious challenge and has to be tackled first by increasing the administrative staff number.

Process error rates in general research applications to the Human Research Ethics Committee (Medical) at the University of the Witwatersrand: A secondary data analysis

Objective. To examine process error rates in applications for ethics clearance of health research. Methods. Minutes of 586 general research applications made to a human health research ethics committee (HREC) from April 2008 to March 2009 were examined. Rates of approval were calculated and reasons for requiring revision or non-approval of the applications were grouped into eight categories. Results. Of the applications, 37% were approved at first evaluation; minor revisions were required for 56% and major revisions for 3%, while 4% were not approved. Eventually 69% of the 586 applications were approved. Surprisingly, 28% were removed from the Committee agenda because of no response from the applicants. Of the 607 instances of process error in 369 applications requiring revision or that were not approved at first evaluation, difficulty with consent documents (55%) and missing information (43%) were the most frequent; the remaining 6 types ranged in frequency from 3% to 17%. Conclusion. It is suggested that the process errors seen could be reduced in rate if applicants were to show a draft of their application to an HREC member or experienced researcher before submission.

Workload of a South African University-based Health Research Ethics Committee in 2003 and 2007

Objective. To compare workloads of a university-based health research ethics committee (medical) for 2003 and 2007. Methods. Minutes and database records of all applications processed by the committee in 2003 and 2007 were examined. Results. General research applications increased from 439 to 553 in 2007 while clinical trial proposals declined from 102 to 86. Some 60 - 70% of applications required revision; 77 - 81% of general research applications and 86 - 97% of clinical trials were eventually approved. Conclusion. The workload puts an increasingly heavy burden on committee members and support staff. South African Journal of Bioethics & Law Vol. 1 (2) 2008: pp. 38-43

The simultaneous quantification of cytochrome P450 dependent linoleate and arachidonate metabolites in urine by HPLC-MS/MS

A method for the simultaneous quantification of urinary linoleic and arachidonic acid derived epoxides and diols, as well as the arachidonate omega hydroxylated product has been developed. The method employs negative mode electrospray ionization and HPLC with tandem mass spectroscopy for quantification. Odd chain length saturated epoxy and dihydroxy fatty acids are used as analytical surrogates resulting in linear calibrations (r (2) > or = 0.9995). Standard addition analyses showed that matrix effects do not prevent these surrogates from yielding reliable quantitative results. Using 4 ml urine aliquots at a final extract volume of 100 micro l and injecting 10 micro l, method detection limits and limits of quantification were < or =0.5 and 1.5 nM, respectively. The sensitivity for dihydroxy lipids was from 3- to 10-fold greater than the corresponding epoxy fatty acid. Shot to shot run times of 31 min were achieved. Rodent and human urine analyses indicated the method sensitivity is sufficient for general research applications. In addition, diurnal fluctuations in linoleate and arachidonate derived metabolites were observed in human subjects.

Multi-Material ALE methods in unstructured grids

Arbitrary Lagrangian Eulerian (ALE) methods have existed for several decades. However, three-dimensional Multi-Material Arbitrary Lagrangian Eulerian (MMALE) methods for unstructured grids are relatively new. MMALE algorithms provide the framework to model sections of a simulation as either Lagrangian, ALE, or Eulerian. In addition, sections of a simulation can switch in time between mesh motions as the distortion of the problem dictates. The MMALE method provides the accuracy of Lagrangian mesh motion and the robustness of Eulerian mesh motion within the same framework. Extending this method to unstructured grids allows for more accurate representation of curved surfaces and complex geometries. This paper examines the algorithms required for the MMALE method and the extensions to these algorithms for unstructured meshes. In addition, second-order behavior of the MMALE algorithm as it exists in the high energy density physics code Arbitrary Lagrangian Eulerian General Research Applications code (ALEGRA) is demonstrated, along with a practical example of its usefulness.