Necessity as a Function of Skewness.

With necessary condition analysis (NCA), a necessity effect is estimated by calculating the amount of empty space in the upper left corner in a plot with a predictor X and an outcome Y. In the present simulation study, calculated necessity effects were found to have a negative association with the skewness of the predictor and a positive association with the skewness of the outcome. Also the standard error of the necessity effect was found to be influenced by the skewness of the predictor and the skewness of the outcome, as well as by sample size, and a way to calculate a confidence interval for the necessity effect is presented. At least some of the findings obtained with NCA are well within the range of what can be expected from the skewness of the predictor and the outcome alone.

Assessment of human platelet survival in the NOD/SCID mouse model: technical considerations.

BACKGROUND: The NOD/SCID mouse model is a unique and sophisticated method to study the survival of human platelets (PLTs) in vivo. Meanwhile, several research groups adopted this model to analyze a wide range of PLT antibodies. Differences exist between the research groups regarding the method of PLT injection, the amount and route of antibody injection, and the preparation of blood samples collected from the animal, making it difficult to compare results between studies. STUDY DESIGN AND METHODS: We compared the survival of human PLTs infused into NOD/SCID mice via the tail vein or the retro-orbital plexus. The percentage of circulating human PLTs in the mouse circulation was determined by flow cytometry. Murine blood samples were prepared using two different methods: 1) direct fixation of whole blood samples and 2) isolation of PLTs by density gradient centrifugation. RESULTS: Recovery of human PLTs after tail vein injection was comparable to retro-orbital injection (13% vs. 11% of all circulating PLTs, p = 0.401). However, the survival rate of tail vein-infused PLTs was higher than that of retro-orbitally injected PLTs (median PLT survival after 5 hr 84% vs. 56%, p = 0.025). Moreover, we observed that determination of circulating human PLTs in directly fixed murine whole blood samples shows better reproducibility compared to the density gradient centrifugation method. CONCLUSIONS: Tail vein injection of human PLTs into the NOD/SCID mice is superior to retro-orbital injection in terms of human PLT survival. Direct fixation of whole blood samples allows better reproducibility of results compared to the density gradient centrifugation method.

Vital-dye enhanced fluorescence imaging of GI mucosa: metaplasia, neoplasia, inflammation.

BACKGROUND: Confocal endomicroscopy has revolutionized endoscopy by offering subcellular images of the GI epithelium; however, the field of view is limited. Multiscale endoscopy platforms that use widefield imaging are needed to better direct the placement of high-resolution probes. DESIGN: Feasibility study. OBJECTIVE: This study evaluated the feasibility of a single agent, proflavine hemisulfate, as a contrast medium during both widefield and high-resolution imaging to characterize the morphologic changes associated with a variety of GI conditions. SETTING: The University of Texas MD Anderson Cancer Center, Houston, Texas, and Mount Sinai Medical Center, New York, New York. PATIENTS, INTERVENTIONS, AND MAIN OUTCOME MEASUREMENTS: Resected specimens were obtained from 15 patients undergoing EMR, esophagectomy, or colectomy. Proflavine hemisulfate, a vital fluorescent dye, was applied topically. The specimens were imaged with a widefield multispectral microscope and a high-resolution microendoscope. The images were compared with histopathologic examination. RESULTS: Widefield fluorescence imaging enhanced visualization of morphology, including the presence and spatial distribution of glands, glandular distortion, atrophy, and crowding. High-resolution imaging of widefield abnormal areas revealed that neoplastic progression corresponded to glandular heterogeneity and nuclear crowding in dysplasia, with glandular effacement in carcinoma. These widefield and high-resolution image features correlated well with the histopathologic features. LIMITATIONS: This imaging approach must be validated in vivo with a larger sample size. CONCLUSIONS: Multiscale proflavine-enhanced fluorescence imaging can delineate epithelial changes in a variety of GI conditions. Distorted glandular features seen with widefield imaging could serve as a critical bridge to high-resolution probe placement. An endoscopic platform combining the two modalities with a single vital dye may facilitate point-of-care decision making by providing real-time, in vivo diagnoses.