Properties of diagnostic data distributions

In applications of statistical methods to medical diagnosis, information on patients' diseases and symptoms is collected and the resulting data-base is used to diagnose new patients. The data-structure is complicated by a number of factors, two of which are examined here: selection bias and unstable population. Under reasonable conditions, no correction for selection bias is required when assessing probabilities for diseases based on symptom information, and it is suggested that these "diagnostic distributions" should form the principal object of study. Transformation of these distributions under changing population structure is considered and shown to take on a simple form in many situations. It is argued that the prevailing paradigm of diagnostic statistics, which concentrates on incidence of symptoms for given disease, is largely inappropriate and should be replaced by an emphasis on diagnostic distributions. The generalized logistic model is seen to fit naturally into the new framework.     

Backscattered electron imaging of the undersurface of resin-embedded cells by field-emission scanning electron microscopy

In this study backscattered electron (BSE) imaging was used to display cellular structures stained with heavy metals within an unstained resin by atomic number contrast in successively deeper layers. Balb/c 3T3 fibroblasts were cultured on either 13-mm discs of plastic Thermanox, commercially pure titanium or steel. The cells were fixed, stained and embedded in resin and the disc removed. The resin block containing the cells was sputter coated and examined in a field-emission scanning electron microscope. The technique allowed for the direct visualization of the cell undersurface and immediately overlying areas of cytoplasm through the surrounding embedding resin, with good resolution and contrast to a significant depth of about 2 μm, without the requirement for cutting sections. The fixation protocol was optimized in order to increase heavy metal staining for maximal backscattered electron production. The operation of the microscope was optimized to maximize the number of backscattered electrons produced and to minimize the spot size. BSE images were collected over a wide range of accelerating voltages (keV), from low values to high values to give ‘sections' of information from increasing depths within the sample. At 3–4 keV only structures a very short distance into the material were observed, essentially the areas of cell attachment to the removed substrate. At higher accelerating voltages information on cell morphology, including in particular stress fibres and cell nuclei, where heavy metals were intensely bound became more evident. The technique allowed stepwise ‘sectional’ information to be acquired. The technique should be useful for studies on cell morphology, cycle and adhesion with greater resolution than can be obtained with any light-microscope-based system.     

Mikrostruktur und Anlaßverhalten aufgedampfter bzw. thermisch gespritzter ZrO2-Schichten auf metallischen Substraten

Microstructure and Tempering Behaviour of Evaporated resp. Thermally Sprayed ZrO₂-Layers on Metallic Substrates Because of their application in gas turbines plasmasprayed thermal barrier coatings of partially stabilized zirconia on metallic substrates are an example for the technical use of ceramic-metal-composites. Problems especially concerning the interface adhesion are still partly not understood. In this paper several systems are examined by electron microscopy, which all consist of ceramic zirconia layers evaporated or thermally sprayed on a metallic substrate. Priority is given to structural analysis. An attempt is made to lighten the interface morphology by the method of cross section preparing, because thereby the possibility of aimed preparation is given.     

First observation of the fourth neutral polarization point in the atmosphere

In the clear sky there are three commonly known loci, the Arago, Babinet, and Brewster neutral points, where the skylight is unpolarized. These peculiar celestial points, bearing the names of their discoverers, have been the subject of many ground-based investigations, because their positions are sensitive indicators of the amount and type of atmospheric turbidity. According to theoretical considerations and computer simulations, there should exist an additional neutral point approximately opposite to the Babinet point, which can be observed only at higher altitudes in the air or space. Until now, this anonymous "fourth" neutral point has not been observed during air- or space-borne polarimetric experiments and has been forgotten, in spite of the fact that the neutral points were a basic tool in atmospheric research for a century. Here, we report on the first observation of this fourth neutral point from a hot air balloon. Using 180 degrees-field-of-view imaging polarimetry, we could observe the fourth neutral point at 450, 550, and 650 nm from different altitudes between 900 and 3500 m during and after sunrise at approximately 22 degrees - 40 degrees below the anti-solar point along the anti-solar meridian, depending on the wavelength and solar elevation. We show that the fourth neutral point exists at the expected location and has characteristics similar to those of the Arago, Babinet, and Brewster points. We discuss why the fourth neutral point has not been observed in previous air- or space-borne polarimetric experiments.     

The effect of converting from pravastatin to simvastatin on the pharmacodynamics of warfarin

Glycosylated amino acids and glycosylated human serum albumin reduce nitrite to nitric oxide under anaerobic conditions. The amount of nitric oxide produced was recorded by generation of nitrosoHb from deoxyHb. Without preincubation after the addition of sodium nitrite, glucose or a mixture of glucose with amino acid or serum albumin did not cause spectrophotometrically detectible transformation of deoxyHb into nitrosoHb. The generation of NO increased with an increase in content of colored "final" products of amino acid and serum albumin glycosylation in the incubation mixture. The incubation of blood plasma of patients with diabetes mellitus with nitrite also resulted in the increased production of NO as compared to blood plasma of healthy subjects. During the incubation of healthy subjects' blood plasma with nitrite a small amount of NO was produced. The removal of low-molecular-weight compounds was accompanied by a significantly decreased generation of NO by blood plasma.     

A Golgi localization signal identified in the Menkes recombinant protein

Menkes disease arises from a genetic impairment in copper transport. The gene responsible for the phenotype has been identified as a copper transporting ATPase ( ATP7A ). Recently, the protein encoded by the ATP7A gene has been localized to the Golgi complex. In order to investigate the role of the Menkes disease protein in copper transport, recombinant constructs containing both the full-length open reading frame and an alternatively spliced form have been successfully expressed and localized in mammalian cells. Other studies of a patient with occipital horn syndrome, an allelic variant of Menkes disease, have demonstrated that only this alternatively spliced isoform and not the full-length form is expressed in this patient. The milder form of this patient's phenotype suggests that the alternatively spliced isoform has some functional role in copper transport. In the present study the full-length recombinant Menkes protein was shown by immunofluorescence to localize to the Golgi apparatus and the alternatively spliced form, lacking sequences for transmembrane domains 3 and 4 encoded by exon 10, was shown to localize to the endoplasmic reticulum. Using sequences from exon 10 fused to a non-Golgi reporter molecule, a 38 amino acid sequence containing transmembrane domain 3 of the Menkes protein was found to be sufficient for localization to the Golgi complex. Therefore, the protein sequence encoded by exon 10 may be responsible for this differential localization and both isoforms may be required for comprehensive transport of copper within the cell.     

Prolonged neuromuscular blockade with mivacurium in a newborn

Recent reports have demonstrated that puerperal psychosis is preceded by prodromic signs. These signs must be recognized in a multidisciplinary context, opening the way to improved diagnosis, therapy and prognosis. On the basis of our clinical experience, we stress the important of early management in women who present prodromic signs of puerperal psychosis. Specific management relies on intensive psychotherapy with daily sessions centered on filiation. With this approach, the emergence of delusions can generally be prevented, usually allowing an uninterrupted mother-infant relationship. We hypothesize that this approach has a favorable influence on later mother-child interactions and cause profound changes in the mother's psychic organization, resulting in a better long-term prognosis. We illustrate our point with a case report.