Point-of-care cell therapy manufacturing; it’s not for everyone

The use of cellular therapies to treat cancer, inherited immune deficiencies, hemoglobinopathies and viral infections is growing rapidly. The increased interest in cellular therapies has led to the development of reagents and closed-system automated instruments for the production of these therapies. For cellular therapy clinical trials involving multiple sites some people are advocating a decentralized model of manufacturing where patients are treated with cells produced using automated instruments at each participating center using a single, centrally held Investigational New Drug Application (IND). Many academic centers are purchasing these automated instruments for point-of-care manufacturing and participation in decentralized multiple center clinical trials. However, multiple site manufacturing requires harmonization of product testing and manufacturing in order to interpret the clinical trial results. Decentralized manufacturing is quite challenging since all centers should use the same manufacturing protocol, the same or comparable in-process and lot release assays and the quality programs from each center must work closely together. Consequently, manufacturing cellular therapies using a decentralized model is in many ways more difficult than manufacturing cells in a single centralized facility. Before an academic center decides to establish a point-of-care cell processing laboratory, they should consider all costs associated with such a program. For many academic cell processing centers, point-of-care manufacturing may not be a good investment.

The IAGOS Research Infrastructure for monitoring atmospheric composition and air quality using commercial aircraft

<p>IAGOS (In-service Aircraft for a Global Observing System) is a European Research Infrastructure for global observations of atmospheric composition using commercial aircraft. Commercial aircraft are ideal platforms for providing long-term in-situ measurements with high vertical and temporal resolution, particularly at cruise altitude (between 9 and 13 km) in the climate-sensitive region of the atmosphere known as the upper troposphere-lower stratosphere (UTLS). IAGOS also provides landing and take-off profiles at almost 300 airports throughout the world which are of major interest for air quality issues. Fully automated instruments are permanently installed on Airbus A330 aircraft operated by different airlines. Data are collected on about 500 flights per aircraft per year. All the aircraft measure the abundances of many essential climate variables, chiefly ozone and the precursor carbon monoxide, water vapour, clouds and meteorological parameters. Additional instruments can be installed to measure nitrogen oxides, aerosols, or the greenhouse gases carbon dioxide and methane. The data are transmitted in near to real real time to weather services and are freely available for the scientific community, national air quality prediction centres and the Copernicus Atmosphere Monitoring Service (CAMS). We describe the importance of these measurements in the monitoring of global atmospheric composition and air quality. I<span>n particular, we show examples from the Copernicus Atmosphere Monitoring Service (CAMS) where IAGOS data are used in the evaluation and improvement of forecasts of air quality over Europe, and discuss how the development of the IAGOS data transmission and instrumentation may fertilize infrastructure development for other airborne platforms.</span></p>

Reliability of Total Nucleated Cell Counts in the Setting of Hip Arthroplasty

Background Total nucleated cell (TNC) count and differential are used to classify joint effusions as inflammatory or noninflammatory. Further diagnostic evaluation and management is contingent on this classification. TNC count can be measured by automated analyzers or by manual assessment using a hemocytometer. Studies have raised concerns regarding the accuracy of TNC counts measured by automated instruments, particularly in the setting of joint arthroplasty. The objective of this study was to determine whether metallosis, a complication of total hip arthroplasty in which metal debris accumulates in periprosthetic tissues and synovial fluid, is associated with inaccurate TNC counts in synovial fluid. Methods We compared the accuracy of cell counts measured by the Sysmex XN-1000 and Beckman Coulter Iris iQ200 with the gold standard of manual assessment using a hemocytometer in synovial fluid from patients with suspected metallosis and in fluid obtained from controls from patients with native joints and a history of arthroplasty for other indications. Results TNC counts produced by automated analyzers were associated with increased levels of discordance (relative to manual counts) in patients with metallosis. Metallosis was not associated with increased levels of discordance for RBC counts or WBC differentials. The Sysmex XN flagged all but 1 metallosis sample for manual verification of the results. Conclusions Automated methods are generally reliable for analysis of synovial fluid. TNC counts can be inaccurate in the context of metallosis following total hip arthroplasty. Laboratories should correlate automated cell counts with a microscopic assessment of the specimen, as recommended by instrument manufacturers.

Evaluation of the WMO Solid Precipitation Intercomparison Experiment (SPICE) transfer functions for adjusting the wind bias in solid precipitation measurements

The World Meteorological Organization (WMO) Solid Precipitation Intercomparison Experiment (SPICE) involved extensive field intercomparisons of automated instruments for measuring snow during the 2013/2014 and 2014/2015 winter seasons. A key outcome of SPICE was the development of transfer functions for the wind bias adjustment of solid precipitation measurements using various precipitation gauge and wind shield configurations. Due to the short intercomparison period, the data set was not sufficiently large to develop and evaluate transfer functions using independent precipitation measurements, although on average the adjustments were effective at reducing the bias in unshielded gauges from −33.4 % to 1.1 %. The present analysis uses data collected at eight SPICE sites over the 2015/2016 and 2016/2017 winter periods, comparing 30 min adjusted and unadjusted measurements from Geonor T-200B3 and OTT Pluvio2 precipitation gauges in different shield configurations to the WMO Double Fence Automated Reference (DFAR) for the evaluation of the transfer function. Performance is assessed in terms of relative total catch (RTC), root mean square error (RMSE), Pearson correlation (r), and percentage of events (PEs) within 0.1 mm of the DFAR. Metrics are reported for combined precipitation types and for snow only. The evaluation shows that the performance varies substantially by site. Adjusted RTC varies from 54 % to 123 %, RMSE from 0.07 to 0.38 mm, r from 0.28 to 0.94, and PEs from 37 % to 84 %, depending on precipitation phase, site, and gauge configuration (gauge and wind screen type). Generally, windier sites, such as Haukeliseter (Norway) and Bratt's Lake (Canada), exhibit a net under-adjustment (RTC of 54 % to 83 %), while the less windy sites, such as Sodankylä (Finland) and Caribou Creek (Canada), exhibit a net over-adjustment (RTC of 102 % to 123 %). Although the application of transfer functions is necessary to mitigate wind bias in solid precipitation measurements, especially at windy sites and for unshielded gauges, the variability in the performance metrics among sites suggests that the functions be applied with caution.

Antifungal Susceptibility Testing: Current Approaches

SUMMARY Although not as ubiquitous as antibacterial susceptibility testing, antifungal susceptibility testing (AFST) is a tool of increasing importance in clinical microbiology laboratories. The goal of AFST is to reliably produce MIC values that may be used to guide patient therapy, inform epidemiological studies, and track rates of antifungal drug resistance. There are three methods that have been standardized by standards development organizations: broth dilution, disk diffusion, and azole agar screening for Aspergillus. Other commonly used methods include gradient diffusion and the use of rapid automated instruments. Novel methodologies for susceptibility testing are in development. It is important for laboratories to consider not only the method of testing but also the interpretation (or lack thereof) of in vitro data.

Basis of legal regulation and Internet censorship in China

This article examines the basis of legal regulation and Internet censorship in China. The genesis, development and relevant regulatory basis of legal regulation of Internet in China is examined. The author comes to the conclusion that on the one hand, Internet in China is subject to tight control due to the rapid development of technologies of observation and increase of police access to user data. Currently, China is one of the leaders in engineering and export of automated instruments for monitoring social networks. The citizens face restrictions based on the control of login accounts that give access to the Internet; blockchain apps and their developers are also subject to control and must provide registration of real names of the users; international corporations, such as Apple, Microsoft, Linkedin, are forced to bend to the demands of Chinese authorities and help to determine and punish the users who do not adhere to the censorship requirements in China. On the other hand, Chinese government makes everything possible for the large scale implementation of information technologies into socioeconomic life of the country, namely industrial and commercial sectors. Usage of internet in the sphere of sociopolitical life restricted, since China justifiably sees a threat to political stability and social security of the country.

Evaluation of the WMO-SPICE transfer functions for adjusting the wind bias in solid precipitation measurements

The World Meteorological Organization (WMO) Solid Precipitation Inter-Comparison Experiment (SPICE) involved extensive field intercomparisons of automated instruments for measuring snow during the 2013/2014 and 2014/2015 winter seasons. A key outcome of SPICE was the development of transfer functions for the wind bias adjustment of solid precipitation measurements using various precipitation gauge and windshield configurations. Due to the short intercomparison period, the dataset was not sufficiently large to develop and evaluate transfer functions using independent precipitation measurements. The present analysis uses data collected at eight SPICE sites over the 2015/2016 and 2016/2017 winter periods, comparing 30-minute adjusted and unadjusted measurements from Geonor T-200B3 and OTT Pluvio2 precipitation gauges in different shield configurations to the WMO Double Fence Automated Reference (DFAR) for the verification of the transfer function. Performance is assessed in terms of relative total catch (RTC), root mean square error (RMSE), and Pearson correlation (r), and Nash-Sutcliffe Efficiency (NSE) for all precipitation types, and for snow only. The evaluation shows that the performance varies substantially by site. Adjusted RTC varies from 54 % to 123 %, RMSE from 0.07 mm to 0.38 mm, and r from 0.28 to 0.94 and NSE from −1.88 to 0.89, depending on precipitation phase, site, and gauge configuration. Generally, windier sites such as Haukeliseter (Norway) and Bratt's Lake (Canada) exhibit a net under-adjustment (17 % to 46 %), while the less windy sites such as Sodankylä (Finland) and Caribou Creek (Canada) exhibit a net over-adjustment (2 % to 23 %). Although the application of transfer functions is necessary to mitigate wind bias in solid precipitation measurements, especially at windy sites and for unshielded gauges, the inconsistency in the performance metrics among sites suggests that the functions be applied with caution.

CPO Complete, a novel test for fast, accurate phenotypic detection and classification of carbapenemases

Rapid, accurate detection of carbapenemase-producing organisms (CPOs) and the classification of their carbapenemases are valuable tools for reducing the mortality of the CPO-associated infections, preventing the spread of CPOs, and optimizing use of new β-lactamase inhibitor combinations such as ceftazidime/avibactam and meropenem/vaborbactam. The current study evaluated the performance of CPO Complete, a novel, manual, phenotypic carbapenemase detection and classification test. The test was evaluated for sensitivity and specificity against 262 CPO isolates of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii and 67 non-CPO isolates. It was also evaluated for carbapenemase classification accuracy against 205 CPOs that produced a single carbapenemase class. The test exhibited 100% sensitivity 98.5% specificity for carbapenemase detection within 90 minutes and detected 74.1% of carbapenemases within 10 minutes. In the classification evaluation, 99.0% of carbapenemases were correctly classified. The test is technically simple and has potential for adaptation to automated instruments. With lyophilized kit storage at temperatures up to 38°C the CPO Complete test has the potential to provide rapid, accurate carbapenemase detection and classification in both limited resource and technologically advanced laboratories.