A Mathematical Framework for Combining Decisions of Multiple Experts toward Accurate and Remote Diagnosis of Malaria Using Tele-Microscopy

We propose a methodology for digitally fusing diagnostic decisions made by multiple medical experts in order to improve accuracy of diagnosis. Toward this goal, we report an experimental study involving nine experts, where each one was given more than 8,000 digital microscopic images of individual human red blood cells and asked to identify malaria infected cells. The results of this experiment reveal that even highly trained medical experts are not always self-consistent in their diagnostic decisions and that there exists a fair level of disagreement among experts, even for binary decisions (i.e., infected vs. uninfected). To tackle this general medical diagnosis problem, we propose a probabilistic algorithm to fuse the decisions made by trained medical experts to robustly achieve higher levels of accuracy when compared to individual experts making such decisions. By modelling the decisions of experts as a three component mixture model and solving for the underlying parameters using the Expectation Maximisation algorithm, we demonstrate the efficacy of our approach which significantly improves the overall diagnostic accuracy of malaria infected cells. Additionally, we present a mathematical framework for performing ‘slide-level’ diagnosis by using individual ‘cell-level’ diagnosis data, shedding more light on the statistical rules that should govern the routine practice in examination of e.g., thin blood smear samples. This framework could be generalized for various other tele-pathology needs, and can be used by trained experts within an efficient tele-medicine platform.     

Estimating recent growth in the cuttlefish Sepia officinalis: are nucleic acid-based indicators for growth and condition the method of choice?

A laboratory calibration study was undertaken with juvenile Sepia officinalis (80-85 g initial wet weight) to investigate the effects of different food rations and different starving intervals on RNA/dry weight (DW) ratios and RNA/DNA ratios in cephalopod mantle muscle at two different temperatures. The digestive gland index was also used as an additional indicator of recent growth. High food rations and low temperature went along with high RNA/DW ratios and high RNA/DNA ratios. Starving resulted in a linear decline in growth performance and a concomitant decrease in RNA/DW and RNA/DNA ratio, with RNA/DNA ratios representing the growth data better. RNA/DNA ratios decreased faster at higher temperatures. A fluorimetric assay for nucleic acid analysis was optimized for cephalopod mantle tissues and yielded reproducible RNA/DNA ratios with a relative variance below 10%. Thus, it may be possible to use this estimator of recently encountered feeding regime for the evaluation of mortality rates of early teuthid paralarvae to eventually support stock management. Also, log relative digestive gland weight showed a strong relationship with starving time, but, surprisingly, not with temperature. Data from the two temperatures analyzed could be combined to form a common regression line of relative digestive gland index with starving time. This indicator for recent growth might be especially suitable for large specimens with a well-developed digestive gland.     

Can zoosporic true fungi grow or survive in extreme or stressful environments?

Zoosporic true fungi are thought to be ubiquitous in many ecosystems, especially in cool, moist soils and freshwater habitats which are rich in organic matter. However, some of the habitats where these fungi are found may periodically experience extreme conditions, such as soils in extremely dry, hot and cold climates, acidic and alkaline soils, polluted rivers, anaerobic soil and water, saline soil and water, periglacial soils, oligotrophic soils, tree canopies and hydrothermal vents. It is clear that many ecotypes of zoosporic true fungi have indeed adapted to extreme or stressful environmental conditions. This conclusion is supported by studies in both the field and in the laboratory. Therefore, in our opinion, at least some true zoosporic fungi can be considered to be extremophiles.     

Patterns of reproduction and development of selected resident teleosts of Florida salt marshes

A wide variety of teleost fishes occur in tidal marshes of Atlantic and Gulf coasts of Florida, few of which breed in these habitats or remain there for extended periods of time. A significant fraction of teleosts that do so are members of one of five families. Eleven representative species belonging to these families, whose reproduction and development are considered here, include: Adinia xenica, Fundulus confluentus, F. grandis and F. similis (Fundulidae); Cyprinodon variegatus, Floridichthys carpio and Jordanella floridae (Cyprinodontidae); Gambusia holbrooki and Poecilia latipinna (Poeciliidae); Mugil cephalus (Mugilidae); and Dormitator maculatus (Eleotridae). Spawning or birth locations, patterns of growth and development, times of use of the salt marsh as a nursery area, and development of salinity tolerances/osmotic regulatory capabilities were evaluated for each, considering these in the context of variability of environmental conditions, especially of salinity. Five different patterns of reproduction are shown by these 11 species, and only A. xenica appears to be limited to reproducing in the salt marsh environment. Some of these species are capable of reproducing throughout the year. Several of the species are annuals, most others live only 2 or 3 years. Eight species (those other than M. cephalus, A. xenica and G. holbrooki) were found to show no size relationship, large juvenile to adult sizes, in osmotic regulatory capabilities.     

Cytokeratin provides a specific marker for human arachnoid cells grown in vitro

Cells from cranial and spinal arachnoid membranes of humans were grown in culture. Their growth characteristics, morphology and details of their cytoskeletal composition are described. Arachnoid membranes, obtained at autopsy, were finely minced and incubated in tissue culture medium. Monolayers of cells of homogeneous morphology grew from these tissue fragments. The cells were flat and polygonal. They divided slowly to form non-overlapping monolayers of low cell density. Electron microscopic examination of cultured arachnoid cells revealed numerous desmosome-like tight junctions and abundant intermediate filaments (tonofilaments). Both morphological features are characteristic of arachnoid cells in situ, but not of cells in the fibroblast-rich dura mater. Immunofluorescence microscopy with monoclonal antibodies demonstrated cytokeratin in the cytoplasm of primary cultures of arachnoid cells. Thus we demonstrated that these cultured cells retained certain of the specific differentiated properties of arachnoid cells in situ and that they are not fibroblasts (which lack tight junctions and cytokeratins). To our knowledge, there have been no previous reports of in vitro growth of arachnoid cells. This in vitro model should be useful in studying the response of arachnoid cells to a variety of substances thought to be involved in the chronic inflammatory condition of the meninges known as arachnoiditis.