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Biomedical subjects

John Pearson

Publications and source records attributed to John Pearson.

7 recordsLinked to original sources

Heterologous expression of mammalian Plk1 in Drosophila reveals divergence from Polo during late mitosis.

Drosophila Polo kinase is the founder member of a conserved kinase family required for multiple stages of mitosis. We assessed the ability of mouse Polo-like kinase 1 (Plk1) to perform the multiple mitotic functions of Polo kinase, by expressing a Plk1-GFP fusion in Drosophila. Consistent with the previously reported localization of Polo kinase, Plk1-GFP was strongly localized to centrosomes and recruited to the centromeric regions of condensing chromosomes during early mitosis. However, in contrast to a functional Polo-GFP fusion, Plk1-GFP failed to localize to the central spindle midzone in both syncytial embryo mitosis and the conventional mitoses of cellularized embryos and S2 cells. Moreover, unlike endogenous Polo kinase and Polo-GFP, Plk1-GFP failed to associate with the contractile ring. Expression of Plk1-GFP enhanced the lethality of hypomorphic polo mutants and disrupted the organization of the actinomyosin cytoskeleton in a dominant-negative manner. Taken together, our results suggest that endogenous Polo kinase has specific roles in regulating actinomyosin rearrangements during Drosophila mitoses that its mammalian counterpart, Plk1, cannot fulfill. Consistent with this hypothesis, we observed defects in the cortical recruitment of myosin and myosin regulatory light chain in Polo deficient cells.

Animals↗

Potential medication dosing errors in outpatient pediatrics.

OBJECTIVE: To determine the prevalence of potential dosing errors of medication dispensed to children for 22 common medications. STUDY DESIGN: Using automated pharmacy data from 3 health maintenance organizations (HMOs), we randomly selected up to 120 children with a new dispensing prescription for each drug of interest, giving 1933 study subjects. Errors were defined as potential overdoses or potential underdoses. Error rate in 2 HMOs that use paper prescriptions was compared with 1 HMO that uses an electronic prescription writer. RESULTS: Approximately 15% of children were dispensed a medication with a potential dosing error: 8% were potential overdoses and 7% were potential underdoses. Among children weighing <35 kg, only 67% of doses were dispensed within recommended dosing ranges, and more than 1% were dispensed at more than twice the recommended maximum dose. Analgesics were most likely to be potentially overdosed (15%), whereas antiepileptics were most likely potentially underdosed (20%). Potential error rates were not lower at the site with an electronic prescription writer. CONCLUSIONS: Potential medication dosing errors occur frequently in outpatient pediatrics. Studies on the clinical impact of these potential errors and effective error prevention strategies are needed.

Adolescent↗

Subwavelength focusing and guiding of surface plasmons.

The constructive interference of surface plasmon polaritons (SPP) launched by nanometric holes allows us to focus SPP into a spot of high near-field intensity having subwavelength width. Near-field scanning optical microscopy is used to map the local SPP intensity. The resulting SPP patterns and their polarization dependence are accurately described in model calculations based on a dipolar model for the SPP emission at each hole. Furthermore, we show that the high SPP intensity in the focal spot can be launched and propagated on a Ag strip guide with a 250 x 50 nm2 cross section, thus overcoming the diffraction limit of conventional optics. The combination of focusing arrays and nano-waveguides may serve as a basic element in planar nano-photonic circuits.

Equipment Design↗

Learning contextual relationships in mammograms using a hierarchical pyramid neural network.

This paper describes a pattern recognition architecture, which we term hierarchical pyramid/neural network (HPNN), that learns to exploit image structure at multiple resolutions for detecting clinically significant features in digital/digitized mammograms. The HPNN architecture consists of a hierarchy of neural networks, each network receiving feature inputs at a given scale as well as features constructed by networks lower in the hierarchy. Networks are trained using a novel error function for the supervised learning of image search/detection tasks when the position of the objects to be found is uncertain or ill defined. We have evaluated the HPNN's ability to eliminate false positive (FP) regions of interest generated by the University of Chicago's (UofC) Computer-aided diagnosis (CAD) systems for microcalcification and mass detection. Results show that the HPNN architecture, trained using the uncertain object position (UOP) error function, reduces the FP rate of a mammographic CAD system by approximately 50% without significant loss in sensitivity. Investigation into the types of FPs that the HPNN eliminates suggests that the pattern recognizer is automatically learning and exploiting contextual information. Clinical utility is demonstrated through the evaluation of an integrated system in a clinical reader study. We conclude that the HPNN architecture learns contextual relationships between features at multiple scales and integrates these features for detecting microcalcifications and breast masses.

Algorithms↗

Wheezing lower respiratory disease and vaccination of full-term infants.

PURPOSE: There have been speculations that increases in vaccinations have caused recent increases in wheezing lower respiratory disease during infancy. We assess possible associations between vaccines and incidence of wheezing in full-term infants. METHODS: We conducted a matched case-control study of full-term infants born into the Kaiser Permanente Northwest health plan during 1991-1994 and continuously enrolled for at least 12 months (n = 1366 case-control pairs). Potential cases of wheeze were ascertained from medical care databases and verified by chart review. Vaccinations, demographic factors, and wheeze risk factors were abstracted from charts. Adjusted relative risks of first onset of wheeze during post-vaccination exposure windows were estimated by conditional logistic regression. We also conducted case-series analyses of wheeze onsets. RESULTS: We found no evidence that risk of wheeze during infancy is associated with recency of vaccination with whole-cell pertussis (DTP), hepatitis b (HBV), Haemophilus influenzae type b (HIB), oral polio (OPV), or measles, mumps and rubella (MMR) vaccines. We also found no evidence that risk of first wheeze is associated with exposure to HBV or MMR. CONCLUSIONS: Recent increases in wheezing during infancy do not appear to be related to increases in vaccinations of full-term infants.

Age Factors↗