Next generation phenotyping in Emanuel and Pallister-Killian syndrome using computer-aided facial dysmorphology analysis of 2D photos.

High throughput approaches are continuously progressing and have become a major part of clinical diagnostics. Still, the critical process of detailed phenotyping and gathering clinical information has not changed much in the last decades. Forms of next generation phenotyping (NGP) are needed to increase further the value of any kind of genetic approaches, including timely consideration of (molecular) cytogenetics during the diagnostic quest. As NGP we used in this study the facial dysmorphology novel analysis (FDNA) technology to automatically identify facial phenotypes associated with Emanuel (ES) and Pallister-Killian Syndrome (PKS) from 2D facial photos. The comparison between ES or PKS and normal individuals expressed a full separation between the cohorts. Our results show that NPG is able to help in the clinic, and could reduce the time patients spend in diagnostic odyssey. It also helps to differentiate ES or PKS from each other and other patients with small supernumerary marker chromosomes, especially in countries with no access to more sophisticated genetic approaches apart from banding cytogenetics. Inclusion of more facial pictures of patient with sSMC, like isochromosome-18p-, cat-eye-syndrome or others may contribute to higher detection rates in future.

Are cancer patients subject to employment discrimination?

We sought to determine whether patients undergoing treatment for cancer had experienced discrimination in employment and, if so, how that discrimination was manifested. We also sought to determine what variables affected the rate of discrimination, including age, gender, occupation, and employer size. We surveyed 422 patients diagnosed with cancer who were being treated at an acute-care, comprehensive cancer center in Houston, Texas, or were being followed after therapy. Whereas 76% of respondents indicated that they were working at the time of diagnosis and 82% said that they wanted to work full- or part-time, only 56% were working at the time of the study. Type of occupation was the main determinant of whether individuals were employed after diagnosis. The study documents self-reported discrimination in employment on the basis of cancer. Additional research is needed to determined the measures, including legal recourse, necessary to enable cancer patients to obtain and continue work.

A model of solar energetic particles for use in calculating LET spectra developed from ONR-604 data.

A model of solar energetic particles (SEP) has been developed and is applied to solar flares during the 1990/1991 CRRES mission using data measured by the University of Chicago instrument, ONR-604. The model includes the time-dependent behavior, heavy-ion content, energy spectrum and fluence, and can accurately represent the observed SEP events in the energy range between 40 to 500 MeV/nucleon. Results are presented for the March and June, 1991 flare periods.

A model of galactic cosmic rays for use in calculating linear energy transfer spectra.

The galactic cosmic rays (GCR) contain fully stripped nuclei, from Hydrogen to beyond the Iron group, accelerated to high energies and are a major component of the background radiation encountered by satellites and interplanetary spacecraft. This paper presents a GCR model which is based upon our current understanding of the astrophysics of GCR transport through interstellar and interplanetary space. The model can be used to predict the energy spectra for all stable and long-lived radioactive species from H to Ni over an energy range from 50 to 50,000 MeV/nucleon as a function of a single parameter, the solar modulation level phi. The details of this model are summarized, phi is derived for the period 1974 to present, and results from this model during the 1990/1991 CRRES mission are presented.

Patulin-induced cellular toxicity: a vital fluorescence study.

The mechanisms of patulin-induced cellular toxicity in an immortalized rat granulosa cell line were examined using several vital fluorescence bioassays. Monochlorobimane and 5-chloromethylfluorescein diacetate were used to monitor cellular glutathione (GSH) levels and revealed dose- and time-dependent depletion of GSH by patulin. A significant reduction in the fluorescence of the monochlorobimane-GSH conjugate by 0.1 microM patulin was observed between 1 and 2 hr. Similar GSH depletion by the mycotoxin was also observed in parallel studies on a liver (Clone 9) and a renal (LLC-PK1) cell line, although reduction of fluorescence occurred within 1 hr at the same dosage. Analysis of the electrical potential-dependent partitioning of rhodamine 123 into mitochondria also revealed significant effects of patulin within 1 hr at 0.1 microM. An initial dose-dependent reduction in mitochondrial fluorescence was followed by loss of selective partitioning of the fluorophore into mitochondria at higher doses and/or a longer exposure of cells to patulin. The reduction in mitochondrial fluorescence was paralleled by a dose-dependent decrease in intracellular pH detected with 2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein. Analysis of [Ca2+]i with indo-1 and fluo-3 revealed a significant dose-dependent influx of Ca2+ at 10 microM and an alteration of the pattern of ionomycin-induced Ca2+ influx at 1.0 microM following patulin treatment. A carboxyfluorescein fluorescence photobleaching assay was used to examine the effects of patulin on gap junction-mediated intercellular communication. Dose-dependent reduction in intercellular communication was observed within 2 hr with 1.0 microM patulin. These observations indicate that the fluorescence assays used in this study provide a sensitive index of toxicity caused by exposure to patulin. Further, the toxic effects of patulin may involve direct effects on cellular glutathione levels and mitochondrial function in addition to direct effects on the plasma membrane.

Removal of cephalosporins by continuous arteriovenous ultrafiltration (CAVU) and hemofiltration (CAVH).

Cephalosporins are used with increasing frequency for sepsis treatment in patients receiving CAVU and CAVH. The different cephalosporins share the same basic molecular structure, yet they exhibit varied extent of plasma protein binding. Different amounts of the antibiotics may be removed by the ultrafiltration procedure because of these variations of physicochemical properties. We evaluated the sieving of eight new cephalosporins across the hemofilter membrane using an in vitro model. Bovine blood was perfused through polysulfone membranes at blood and ultrafiltrate flow rates of 100 and 20 ml/min respectively. Arterial plasma, venous plasma and ultrafiltrate drug concentrations were used to determine sieving coefficients. The sieving coefficients correlated well with the ultrafiltrate-arterial plasma drug concentration ratio (r = 0.679-0.972) but poorly with the extent of protein binding. Factors other than protein binding may therefore affect the drug sieving. Based on the findings, it was predicted that 0.2-21.9% of the daily cephalosporin dose may be removed by the CAVU and CAVH treatment. The need to alter drug dosages depends on the techniques of the ultrafiltration and hemofiltration procedure, the kinetics of the cephalosporins in patients, the sensitivity of the pathogen and the nature of the infection.

Citation analysis of the field of medical decision making: update, 1959-1985.

This article updates a prior citation analysis of medical decision making, published in this journal in 1984. Building on the original core list, decision making papers were added based on any of three criteria: citation of three papers already on the list, identification by a MEDLINE search (CATLINE for books) as relevant to the topic, or mention in a recent review article on decision analysis. The revised core list contains 105 articles and five books. The changes in the field of medical decision making from 1978 to 1981 are reviewed, and key areas of development are identified by co-citation clustering.

Saturnian trapped radiation and its absorption by satellites and rings: the first results from pioneer 11.

Electrons and protons accelerated and trapped in a Saturnian magnetic field have been found by the University of Chicago experiments on Pioneer 11 within 20 Saturn radii (Rs) of the planet. In the innermost regions, strong absorption effects due to satellites and ring material were observed, and from approximately 4 Rs inwards to the outer edge of the A ring at 2.30 Rs (where the radiation is absorbed), the intensity distributions of protons (>/= 0.5 million electron volts) and electrons (2 to 20 million electron volts) were axially symmetric, consistent with a centered dipole aligned with the planetary rotation axis. The maximum fluxes observed for protons (> 35 million electron volts and for electrons < 3.4 million electron volts) were 3 x 10(4) and 3 x 10(6) per square centimeter per second, respectively. Absorption of radiation by Mimas provides a means of estimating the radial diffusion coefficient for charged particle transport. However, the rapid flux increases observed between absorption features raise new questions concerning the physics of charged particle transport and acceleration. An absorption feature near 2.5 Rs has led to the discovery of a previously unknown satellite with a diameter of approximately 200 kilometers, semimajor axis of 2.51 Rs, and eccentricity of 0.013. Radiation absorption features that suggest a nonuniform distribution of matter around Saturn have also been found from 2.34 to 2.36 Rs, near the position of the F ring discovered by the Pioneer imaging experiment. Beneath the A, B, and C rings we continued to observe a low flux of high-energy electrons. We conclude that the inner Saturn magnetosphere, because of its near-axial symmetry and the many discrete radiation absorption regions, offers a unique opportunity to study the acceleration and transport of charged particles in a planetary magnetic field.

Jupiter revisited: first results from the university of chicago charged particle experiment on pioneer 11.

During the December 1974 Pioneer 11 Jupiter encounter our experiment provided measurements of Jovian energetic protons and electrons both in the magnetic equatorial zone and at previously unexplored high magnetic latitudes. Many of the observations and conclusions from the Pioneer 10 encounter in 1973 were confirmed, with several important exceptions and new findings. We report evidence from Pioneer 11 for protons ( approximately 1 million electron volts) of Jovian origin in interplanetary space. In the outer magnetosphere particle intensities at high magnetic latitudes were comparable to those observed in the equatorial zone, and 10-hour variations in particle intensities and spectra were observed at both high and low magnetic latitudes. Therefore, confinement of particles in the outer magnetosphere to a thin equatorial magnetodisc is adequate neither as a description of the particle distribution nor as a complete explanation of the 10-hour variations. Pioneer 11 data support a model in which the intensity varies with a 10-hour period in phase throughout the sunward side of the magnetosphere and is relatively independent of position within the magnetosphere. Transient, highly anisotropic bursts of protons with energies of approximately 1 million electron volts observed near the orbit of Ganymede suggest local acceleration in some regions of the magnetosphere. In the inner core where particles are stably trapped, a maximum in the high-energy nucleonic flux was again found, corresponding to the Pioneer 10 maximum at approximately 3.4 Jupiter radii (R(J)), which is apparently a persistent feature of, the inner radiation zone. In addition, Pioneer 11 data indicate two more local maxima in the nucleonic flux inside 3.4 R(J), one of which may be associated with absorption by Amalthea, and a maximum intensity at 1.9 R(J) more than 20 times that at 3.4 R(J), The flux of relativistic electrons reached a maximum on the magnetic equator at 1.8 R(J), only slightly less its closest approach at 3.1 R(J).

Protons and Electrons in Jupiter's Magnetic Field: Results from the University of Chicago Experiment on Pioneer 10.

Fluxes of high energy electrons and protons are found to be highly concentrated near the magnetic equatorial plane from distances of ~ 30 to ~ 100 Jovian radii (R(J)). The 10-hour period of planetary rotation is observed as an intensity variation, which indicates that the equatorial zone of high particle fluxes is inclined with respect to the rotation axis of the planet. At radial distances [unknown] 20 R(J) the synchrotron-radiation-producing electrons with energies greater, similar 3 million electron volts rise steeply to a maximum intensity of ~ 5 x 10(8) electrons per square centimeter per second near the periapsis at 2.8 R(J). The flux of protons with energies greater, similar 30 million electron volts reaches a maximum intensity of ~ 4 x 10(6) protons per square centimeter per second at ~ 3.5 R(J) with the intensity decreasing inside this radial distance. Only for radial distances [unknown] 20 R(J) does the radiation behave in a manner which is similar to that at the earth. Burst of electrons with energies up to 30 million electron volts, each lasting about 2 days, were observed in interplanetary space beginning approximately 1 month before encounter. This radiation appears to have escaped from the Jovian bow shock or magnetosphere.