Instrumentation and Analyses for Multi-Angle Light Scatter Measurements in Flow Cytometry

MULTIPARAMETER FLOW CYTOMETRIC INSTRUMENTATION HAS BEEN DESIGNED AND CONSTRUCTED IN COLLABORATION BETWEEN JRC-ISPRA AND THE DEPARTMENT OF PHYSICS AND APPLIED PHYSICS, UNIVERSITY OF STRATHCLYDE TO ALLOW THE EXTENSION OF SINGLE CELL DIFFRACTOMETRY TO FLOW SYSTEMS. THE SYSTEM MEASURES UP TO 16 PARAMETERS SIMULTANEOUSLY, OF WHICH 2 MAY BE FLUORESCENCE EMISSION AND THE REMAINDER LIGHT SCATTER IN UP TO 16 ANGULAR WINDOWS IN THE FORWARD AND 90 DEGREES DIRECTIONS. THE INSTRUMENTATION UTILISES PHOTODIODE ARRAYS WHICH ARE SO MOUNTED AS TO ALLOW USER SELECTION OF THE ANGULAR ACCEPTANCE WINDOWS OF THE DETECTORS. THIS FACILITATES THE DISTIN- CTION OF ALGAL GENERA ON THE BASIS OF MORPHOLOGICAL CHARACTERISTICS, THUS WIDENING THE FIELD OF POSSIBLE ECONOLOGICAL APPLICATIONS OF FLOW CYTOMETRY. LABORATORY EXPERIMENTS HAVE BEEN PERFORMED IN ORDER TO TEST THE DESCRIMINA- TORY ABILITY OF THE TECHNIQUE USING BOTH MARINE AND FRESHWATER ALGAE AND ALSO TO ASSESS ITS VALUE FOR APPLICATION TO MULTI-SPECIES BIOASSAYS. IN ADDITION, METHODS OF DATA ANALYSIS ARE UNDER DEVELOPMENT WHICH SHOULD BE APPLICABLE IN OTHER FIELDS OF MULTIPARAMETER FLOW CYTOMETRY. TO DATE DISCRIMINANT ANALYSIS TECHNIQUES HAVE BEEN DEVELOPED WHICH ALLOW DISTIN- CTION AMONG CERTAIN CLASSES OF ALGAE, BUT FURTHER DEVELOPMENT IS NECESSARY.NA-NOT AVAILABL

Preclinical studies on the use of interstitial laser photocoagulation in the lung parenchyma

A preliminary assessment was made of the effect of interstitial laser photocoagulation on normal lung parenchyma. Using rats lesions were created by passing the laser fiber percutaneously into the normal lung under general anaesthetic. The lungs were removed post mortem at 3 days. The lesions were ellipsoid in shape and well circumscribed. Histology showed central charring surrounded by zones of coagulative and hemorrhagic necrosis. there was a clear margin between the treated and normal tissue. These results indicate that further examination is warranted of the use of ILP for treatment of small primary lung tumors in patients unsuitable for surgery

Repeatability and Response to Therapy of Dynamic Contrast-Enhanced Magnetic Resonance Imaging Biomarkers in Rheumatoid Arthritis in a Large Multicentre Trial Setting.

Objectives To determine the repeatability, and response to therapy, of Dynamic Contrast-Enhanced (DCE) MRI biomarkers of synovitis in hand and wrist of Rheumatoid Arthritis (RA) patients, and in particular the performance of the transfer constant Ktrans, in a multicentre trial setting Methods DCE-MRI and RA MRI scoring (RAMRIS) were performed with meticulous standardisation at baseline, 6 and 24 weeks in a sub-study of fostamatinib monotherapy in reducing synovitis compared with placebo or adalimumab. Analysis employed statistical shape modelling to avoid biased regions-of-interest, kinetic modelling and heuristic analyses. Repeatability was also evaluated. Results At early study termination, DCE-MRI data had been acquired from 58 patients in 19 imaging centres. Ktrans intra-subject coefficient of variation (N=14) was 30%. Ktrans change demonstrated inferiority of fostamatinib (N=11) relative to adalimumab (N=10) after 6 weeks (treatment ratio=1.92, p=0.003), and failed to distinguish fostamatinib from placebo (N=10, p=0.79). RAMRIS showed superiority of fostamatinib relative to placebo at 6 weeks (p=0.023), and did not distinguish fostamatinib from adalimumab at either 6 weeks (p=0.175) or 24 weeks (p=0.230). Conclusion This demonstrated repeatability of Ktrans, and its ability to distinguish treatment groups, show that DCE-MRI biomarkers are suitable for use in multicentre RA trials