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This study assessed the impact of an "active learning" strategy employed alone or in combination with traditional lectures on the learning of mammalian physiology by undergraduate students. The study investigated the impact of three teaching strategies, namely (1) traditional lecture, (2) group discussion alone, and (3) combination of lecture and group discussion. For all strategies, students were given homework in a textbook and they completed written assignments before each session. Every student led the discussion of at least one assigned theme during each group session. The students had no access to the textbook or notes during group discussions. Four examinations (3 in-semester and a final) assessed the students' knowledge of fundamental concepts of physiology of specific organ systems. Part of the final examination reassessed knowledge of previously tested topics. The results show that the teaching modality employed to introduce physiology topics influenced students' learning. The average marginal effect of the lecture þ discussion modality (average improvement linked to lecture þ discussion strategy) on students' performance was 6.45% [95% confidence interval (CI[subscript 95]) (4.73, 8.16), P = 1.74 10[superscript -13]], and the average improvement associated with the discussion-only modality was 5.5% [CI[subscript 95] (3.84, 7.16), P = 7.84 10[superscript -11]]. On average, all class ranks performed better on materials covered under active learning settings than under lecture-only conditions. Moreover, students' performance under combined lecture and discussion conditions is predictive of their overall performance in the course. The results support the positive effect of student-centered learning and demonstrate the efficacy of a combination of lectures and group discussions on learning of physiology by nonmajor students.

BackgroundComparing phenotypes of heterogeneous cell populations from multiple biological conditions is at the heart of scientific discovery based on flow cytometry (FC). When the biological signal is measured by the average expression of a biomarker, standard statistical methods require that variance be approximately stabilized in populations to be compared. Since the mean and variance of a cell population are often correlated in fluorescence-based FC measurements, a preprocessing step is needed to stabilize the within-population variances.ResultsWe present a variance-stabilization algorithm, called flowVS, that removes the mean-variance correlations from cell populations identified in each fluorescence channel. flowVS transforms each channel from all samples of a data set by the inverse hyperbolic sine (asinh) transformation. For each channel, the parameters of the transformation are optimally selected by Bartlett's likelihood-ratio test so that the populations attain homogeneous variances. The optimum parameters are then used to transform the corresponding channels in every sample. flowVS is therefore an explicit variance-stabilization method that stabilizes within-population variances in each channel by evaluating the homoskedasticity of clusters with a likelihood-ratio test. With two publicly available datasets, we show that flowVS removes the mean-variance dependence from raw FC data and makes the within-population variance relatively homogeneous. We demonstrate that alternative transformation techniques such as flowTrans, flowScape, logicle, and FCSTrans might not stabilize variance. Besides flow cytometry, flowVS can also be applied to stabilize variance in microarray data. With a publicly available data set we demonstrate that flowVS performs as well as the VSN software, a state-of-the-art approach developed for microarrays.ConclusionsThe homogeneity of variance in cell populations across FC samples is desirable when extracting features uniformly and comparing cell populations with different levels of marker expressions. The newly developed flowVS algorithm solves the variance-stabilization problem in FC and microarrays by optimally transforming data with the help of Bartlett's likelihood-ratio test. On two publicly available FC datasets, flowVS stabilizes within-population variances more evenly than the available transformation and normalization techniques. flowVS-based variance stabilization can help in performing comparison and alignment of phenotypically identical cell populations across different samples. flowVS and the datasets used in this paper are publicly available in Bioconductor.

We describe algorithms for discovering immunophenotypes from large collections of flow cytometry samples and using them to organize the samples into a hierarchy based on phenotypic similarity. The hierarchical organization is helpful for effective and robust cytometry data mining, including the creation of collections of cell populations' characteristic of different classes of samples, robust classification, and anomaly detection. We summarize a set of samples belonging to a biological class or category with a statistically derived template for the class. Whereas individual samples are represented in terms of their cell populations (clusters), a template consists of generic meta-populations (a group of homogeneous cell populations obtained from the samples in a class) that describe key phenotypes shared among all those samples. We organize an FC data collection in a hierarchical data structure that supports the identification of immunophenotypes relevant to clinical diagnosis. A robust template-based classification scheme is also developed, but our primary focus is in the discovery of phenotypic signatures and inter-sample relationships in an FC data collection. This collective analysis approach is more efficient and robust since templates describe phenotypic signatures common to cell populations in several samples while ignoring noise and small sample-specific variations. We have applied the template-based scheme to analyze several datasets, including one representing a healthy immune system and one of acute myeloid leukemia (AML) samples. The last task is challenging due to the phenotypic heterogeneity of the several subtypes of AML. However, we identified thirteen immunophenotypes corresponding to subtypes of AML and were able to distinguish acute promyelocytic leukemia (APL) samples with the markers provided. Clinically, this is helpful since APL has a different treatment regimen from other subtypes of AML. Core algorithms used in our data analysis are available in the flowMatch package at www.bioconductor.org. It has been downloaded nearly 6,000 times since 2014.

We describe a model-based instrument design combined with a statistical classification approach for the development and realization of high speed cell classification systems based on light scatter. In our work, angular light scatter from cells of four bacterial species of interest, Bacillus subtilis, Escherichia coli, Listeria innocua, and Enterococcus faecalis, was modeled using the discrete dipole approximation. We then optimized a scattering detector array design subject to some hardware constraints, configured the instrument, and gathered experimental data from the relevant bacterial cells. Using these models and experiments, it is shown that optimization using a nominal bacteria model (i.e., using a representative size and refractive index) is insufficient for classification of most bacteria in realistic applications. Hence the computational predictions were constituted in the form of scattering-data-vector distributions that accounted for expected variability in the physical properties between individual bacteria within the four species. After the detectors were optimized using the numerical results, they were used to measure scatter from both the known control samples and unknown bacterial cells. A multivariate statistical method based on a support vector machine (SVM) was used to classify the bacteria species based on light scatter signatures. In our final instrument, we realized correct classification of B. subtilis in the presence of E. coli, L. innocua, and E. faecalis using SVM at 99.1%, 99.6%, and 98.5%, respectively, in the optimal detector array configuration. For comparison, the corresponding values for another set of angles were only 69.9%, 71.7%, and 70.2% using SVM, and more importantly, this improved performance is consistent with classification predictions. OCIS codes: 170.1530, 120.5820, 290.5850.