Neurosurgical research in Southeast Asia: A bibliometric analysis.

OBJECTIVES: Bibliometric analysis can provide insight into the growth, development and dissemination of research in neurosurgery. Little work has been done to examine the role of country-specific characteristics affecting research productivity. We aimed to characterize andcompare the research productivity among SEA countries in terms of bibliometric indicesand determine associations with country-specific factors. METHODS: We performed a systematic search of all articles by authors affiliated with a neurosurgical department in any of the Southeast Asian countries, indexed in 3 databases from inception to June 10, 2020. Bibliometric indices - number of publications, number of citations, average citations per publication, h-index, and the i-10-index - were computed for each country. Correlations between the indices and country-specific characteristics (population size, GDP per capita, percentage of GDP allocation to research and development (R&D), number of neurosurgeons, number of neurosurgeons per capita, and number of collaborations with non-SEA authors) were determined. RESULTS: The number of publications showed an increasing trend up to 2019. Most studies were cohort studies (37%) or case reports or series (37%). Of the country-specific factors analyzed, only percentage of the GDP allocated to R&D was positively correlated with number of publications (p = 0.0004), total citations (p < 0.0001), H-index (p < 0.0001), and i(10)-index (p < 0.0001). Number of collaborations also positively correlated with the same indices. CONCLUSION: Our bibliometric analysis showed increasing contribution by neurosurgeons in the SEA region. Correlational analysis support the view that increased R&D budget allocation and international collaboration can improve neurosurgical research capacity and productivity.

Automated pH and conductivity conditioning using feedback control to support a two-step continuous purification process.

As discovery research organizations push more molecules and new modalities through their company pipelines, there comes a need to widen purification development and production bandwidth by increasing automation and throughput. Continuous processing technologies have the unique property of reducing manufacturing floor space and reducing costs. We can speed development and production by implementing automation and continuous process technologies early in discovery research. Here we describe an automated continuous instrument made up of an ÄKTA™ pcc for initial capture by protein A, an ÄKTA pure 150 retrofitted to automatically condition protein A eluate, and a second ÄKTA pure 150 built for flow-through anion exchange chromatography. The continuous instrument we have designed and built recirculates protein A eluate from the ÄKTA pcc in a closed loop while signals from the pH and conductivity meters direct addition of titrant for accurate and precise adjustments to the pH and salt concentration. The instrument is run without user intervention and can be used continuously for production or for development as a tool for screening running conditions on the anion exchange step.

Definition and dynamic control of a continuous chromatography process independent of cell culture titer and impurities.

Advances in cell culture technology have enabled the production of antibody titers upwards of 30g/L. These highly productive cell culture systems can potentially lead to productivity bottlenecks in downstream purification due to lower column loadings, especially in the primary capture chromatography step. Alternative chromatography solutions to help remedy this bottleneck include the utilization of continuous processing systems such as periodic counter-current chromatography (PCC). Recent studies have provided methods to optimize and improve the design of PCC for cell culture titers up to about 3g/L. This paper defines a continuous loading strategy for PCC that is independent of cell culture background and encompasses cell culture titers up to about 31g/L. Initial experimentation showed a challenge with determining a difference in change in UV280nm signal (ie. ΔUV) between cell culture feed and monoclonal antibody (mAb) concentration. Further investigation revealed UV280nm absorbance of the cell culture feedstock without antibody was outside of the linear range of detection for a given cell pathlength. Additional experimentation showed the difference in ΔUV for various cell culture feeds can be either theoretically predicted by Beer's Law given a known absorbance of the media background and impurities or experimentally determined using various UV280nm cell pathlengths. Based on these results, a 0.35mm pathlength at UV280nm was chosen for dynamic control to overcome the background signal. The pore diffusion model showed good agreement with the experimental frontal analysis data, which resulted in definition of a ΔUV setpoint range between 20 and 70% for 3C-PCC experiments. Product quality of the elution pools was acceptable between various cell culture feeds and titers up to about 41g/L. Results indicated the following ΔUV setpoints to achieve robust dynamic control and maintain 3C-PCC yield: ∼20-45% for titers greater than 10g/L depending on UV absorbance of the HCCF and ∼45-70% for titers of up to 10g/L independent of UV absorbance of the HCCF. The strategy and results presented in this paper show column loading in a continuous chromatography step can be dynamically controlled independent of the cell culture feedstock and titer, and allow for enhanced process control built into the downstream continuous operations.