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Biomedical subjects

A A King

Publications and source records attributed to A A King.

At least 19 recordsLinked to original sources
PubMed2006

Inference for nonlinear dynamical systems.

Nonlinear stochastic dynamical systems are widely used to model systems across the sciences and engineering. Such models are natural to formulate and can be analyzed mathematically and numerically. However, difficulties associated with inference from time-series data about unknown parameters in these models have been a constraint on their application. We present a new method that makes maximum likelihood estimation feasible for partially-observed nonlinear stochastic dynamical systems (also known as state-space models) where this was not previously the case. The method is based on a sequence of filtering operations which are shown to converge to a maximum likelihood parameter estimate. We make use of recent advances in nonlinear filtering in the implementation of the algorithm. We apply the method to the study of cholera in Bangladesh. We construct confidence intervals, perform residual analysis, and apply other diagnostics. Our analysis, based upon a model capturing the intrinsic nonlinear dynamics of the system, reveals some effects overlooked by previous studies.

Cholera↗
PubMed2006

The role of surgical biopsy in the diagnosis of glioma in individuals with neurofibromatosis-1.

Most gliomas in neurofibromatosis type 1 (NF1) are pilocytic astrocytomas (PAs) of the optic pathway occurring in young children. However, some individuals develop gliomas that lack the typical NF1-associated clinical features or radiographic appearance. We identified 17 atypical presentations from a review of 100 patients with NF1-associated gliomas. Biopsy showed that 9 were not classic PAs. These data highlight the value of biopsy in NF1-associated gliomas with unusual clinical or radiographic presentations.

Adolescent↗
PubMed2001

Lattice effects observed in chaotic dynamics of experimental populations.

Animals and many plants are counted in discrete units. The collection of possible values (state space) of population numbers is thus a nonnegative integer lattice. Despite this fact, many mathematical population models assume a continuum of system states. The complex dynamics, such as chaos, often displayed by such continuous-state models have stimulated much ecological research; yet discrete-state models with bounded population size can display only cyclic behavior. Motivated by data from a population experiment, we compared the predictions of discrete-state and continuous-state population models. Neither the discrete- nor continuous-state models completely account for the data. Rather, the observed dynamics are explained by a stochastic blending of the chaotic dynamics predicted by the continuous-state model and the cyclic dynamics predicted by the discrete-state models. We suggest that such lattice effects could be an important component of natural population fluctuations.

Animals↗
PubMed2000

Malignant peripheral nerve sheath tumors in neurofibromatosis 1.

One of the most clinically aggressive cancers associated with neurofibromatosis 1 (NF1) is the malignant peripheral nerve sheath tumor (MPNST). To determine the incidence and relative risk (RR) of MPNSTs in individuals with NF1, 1,475 individuals with NF1 were included from a cohort of patients examined by a single experienced geneticist from 1977 to 1996. The end points were incidence of MPNST, relative risk of MPNST, and relative risk associated with specific NF1 physical findings. Thirty-four individuals were identified with MPNST (2%). The relative risk of MPNST was higher than expected with an RR value of 113 (95% confidence interval [CI] = 78-158). The average 10-year annual incidence of MPNST between the second and fifth decade of life was roughly the same with a range of 0.0013 and 0.0068 MPNST per patient year. Most lesions occurred in the limbs (n = 18; 53%), and those with limb lesions survived longer than those with nonlimb MPNSTs. Pain associated with a mass was the greatest risk factor associated with MPNST development (RR = 31.4; 95% CI = 13.2-75.1). Further biological and epidemiological studies are needed to determine other factors that influence the risk of MPNST development in individuals affected with NF1. Am. J. Med. Genet. 93:388-392, 2000. Published 2000 Wiley-Liss, Inc.

Adolescent↗
PubMed2000

Hypoglycemia in Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome associated with macrosomia, macroglossia, abdominal wall defects, hypoglycemia in the neonatal period and embryonal cancers of infancy and early childhood. The frequency of hypoglycemia in this population is between 30% and 50%. The majority of infants with hypoglycemia will be asymptomatic and have resolution of the hypoglycemia within the first 3 days of life. Less than 5% will have hypoglycemia beyond the neonatal period requiring either continuous feeding or a partial pancreatectomy. The cause of hypoglycemia is unclear, but direct and indirect evidence supports a hyperinsulinemia as the major factor. Recent identification of the majority of genes associated with BWS in the 11p15 region and the genotype of persistent hyperinsulinemia hypoglycemia of childhood also in the 11p15 region may provide a molecular basis for hypoglycemia in BWS, particularly for the occasional patients with hypoglycemia requiring a partial pancreatectomy. Detailed genotype phenotype evaluations are needed and should provide an insight as to why patients with BWS have hypoglycemia.

Beckwith-Wiedemann Syndrome↗
PubMed1999

The rainbow bridge: Hamiltonian limits and resonance in predator-prey dynamics.

In the presence of seasonal forcing, the intricate topology of non-integrable Hamiltonian predator-prey models is shown to exercise profound effects on the dynamics and bifurcation structure of more realistic schemes which do not admit a Hamiltonian formulation. The demonstration of this fact is accomplished by writing the more general models as perturbations of a Hamiltonian limit, ℋ, in which are contained infinite numbers of periodic, quasiperiodic and chaotic motions. From ℋ, there emanates a surface, Gamma, of Nejmark-Sacker bifurcations whereby the annual oscillations induced by seasonality are destabilized. Connecting Gamma and ℋ is a bridge of resonance horns within which invariant motions of the Hamiltonian case persist. The boundaries of the resonance horns are curves of tangent (saddle-node) bifurcations corresponding to subharmonics of the yearly cycle. Associated with each horn is a rotation number which determines the dominant frequency, or "color", of attractors within the horn. When viewed through the necessarily coarse filter of ecological data acquisition, and regardless of their detailed topology, these attractors are often indistinguishable from multi-annual cycles. Because the tips of the horns line up monotonically along Gamma, it further follows that the distribution of observable periods in systems subject to fluctuating parameter values induced, for example, by year-to-year variations in the climate, will often exhibit a discernible central tendency. In short, the bifurcation structure is consistent with the observation of multi-annual cycles in Nature. Fundamentally, this is a consequence of the fact that the bridge between ℋ and Gamma is a rainbow bridge. While the present analysis is principally concerned with the two species case (one predator and one prey), Hamiltonian limits are also observed in other ecological contexts: 2n-species (n predators, n prey) systems and periodically-forced three level food chain models. Hamiltonian limits may thus be common in models involving the destruction of one species by another. Given the oft-commented upon structural instability of Hamiltonian systems and the corresponding lack of regard in which they are held as useful caricatures of ecological interactions, the pivotal role assigned here to Hamiltonian limits constitutes a qualitative break with the conventional wisdom.

Animals↗
PubMed1996

Ten-year survey of British bats for the existence of rabies.

In 1985, a notable increase in the number of recorded cases of rabies in European bats was observed, indicating a possible spread of the rabies virus in these bats. Because of concern that the disease could be introduced into the United Kingdom by bats crossing from mainland Europe, a programme of screening dead bats for the presence of rabies and rabies-related viruses was initiated at the Rabies Research and Diagnostic Unit at the Central Veterinary Laboratory. Over a period of 10 years (January 1986 to December 1995), 1882 bats belonging to 23 species from all parts of England, Scotland and Wales have been screened for rabies antigen. All of these bats were found to be negative. Forty-one serotine bats (Eptesicus serotinus), the species of bat most commonly infected in Europe, were included in the total. Subsequent to this survey, in June 1996, a European bat lyssavirus 2 was isolated from a Daubenton's bat (Myotis daubentonii) in Newhaven, East Sussex. It is possible that this bat originated from mainland Europe but this cannot be established with certainty.

Animals↗
PubMed1996

Rabies and mortality in Ethiopian wolves (Canis simensis).

Between October 1991 and February 1992, 41 of 53 known adult and subadult Ethiopian wolves (Canis simensis) in five adjacent packs in the Bale Mountains National Park, Ethiopia, died or disappeared. Brain smears from two carcasses were positive for rabies by the immunofluorescence test, and rabies virus was isolated from the brains by mouse inoculation. Based on monoclonal antibody tests on the mouse brains, we identified the virus as a minor variant of the serotype 1 rabies viruses found in domestic dogs and wild canids of Africa. Sera from two of 15 Ethiopian wolves had rabies virus neutralizing antibody.

Animals↗
PubMed1995

Efficacy of SAD (Berne) rabies vaccine given by the oral route in two species of jackal (Canis mesomelas and Canis adustus).

Eight black-backed jackals (Canis mesomelas) and seven side-striped jackals (Canis adustus) were given SAD (Berne) rabies vaccine by direct oral instillation. Three different vaccine doses were used: 10(6.3), 10(6.8) and 10(7.5) median tissue culture infectious doses. Two additional jackals were given vaccine in chicken heads. One group of jackals was challenged with a lethal dose of jackal-derived rabies virus 1 mo after vaccination and a second group 12 mo after vaccination. All 17 vaccinated jackals developed high and persistent serum neutralizing antibody titers. All challenged jackals resisted a lethal dose of rabies virus, whereas three control jackals given the same challenge succumbed to rabies.

Administration, Oral↗
PubMed1994

Rabies virus typing--preliminary survey in Botswana.

A survey was made of the subtypes of rabies isolates made in Botswana using monoclonal antibodies. Two subtypes were detected, termed canine and mongoose. The canine subtype predominated in the north and west and appeared to be related to the distribution of both the domestic dog and wild jackal. The mongoose subtype was found in the south-east and was associated with feline and viverrid wildlife. The geographical distribution also matched reports of isolates examined in the neighbouring countries.

Animals↗
PubMed1994

Localization of the genetic locus for Saethre-Chotzen syndrome to a 6 cM region of chromosome 7 using four cases with apparently balanced translocations at 7p21.2.

Saethre-Chotzen syndrome is a common autosomal dominant form of craniosynostosis, which results in the premature fusion of cranial sutures. Craniosynostosis is commonly associated with abnormalities of 7p; Vortkamp et al. (Nature 352, 539-540) demonstrated that the GLI3 gene in 7p13 was disrupted in, patients with Greig syndrome and, more recently, the linkage of genetic markers from 7p with the Saethre-Chotzen syndrome locus has been reported (2,3). Here we report the analysis by fluorescence in situ hybridization of four patients with Saethre-Chotzen syndrome associated with apparently balanced translocations involving band 7p21.2 and different reciprocal chromosomes. We show that in all four patients the breakpoints in 7p are situated within a 6 cM region flanked by the genetic markers D7S488 and D7S493. These results provide further evidence that the genetic locus for Saethre-Chotzen syndrome is located in distal 7p.

Acrocephalosyndactylia↗
PubMed1993

Gene targeting of X chromosome-linked chronic granulomatous disease locus in a human myeloid leukemia cell line and rescue by expression of recombinant gp91phox.

The X chromosome-linked chronic granulomatous disease (X-CGD) locus, which encodes the gp91phox subunit of the phagocyte respiratory-burst oxidase cytochrome b, was disrupted by homologous recombination in the PLB-985 human myeloid cell line to develop an in vitro model of X-CGD. Superoxide formation was absent in targeted cells after differentiation to granulocytes but was rescued by stable transfection and expression of wild-type gp91phox cDNA. The targeted cell line should be useful in experiments aimed at defining functional regions within gp91phox by expression of mutant gp91phox cDNAs, complementing studies of naturally occurring mutations in X-CGD. In addition, the mutant line provides a model system in which to establish an experimental basis for the treatment of X-CGD patients with gene replacement therapy. Rescued clones containing even modest amounts of recombinant gp91phox had respiratory-burst activity comparable to the wild-type PLB-985 line, suggesting that functional correction of X-CGD neutrophils may not require high-level expression of gp91phox.

Blotting, Northern↗
PubMed1993

Mouse GATA-4: a retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart.

We report the cDNA cloning and characterization of mouse GATA-4, a new member of the family of zinc finger transcription factors that bind a core GATA motif. GATA-4 cDNA was identified by screening a 6.5-day mouse embryo library with oligonucleotide probes corresponding to a highly conserved region of the finger domains. Like other proteins of the family, GATA-4 is approximately 50 kDa in size and contains two zinc finger domains of the form C-X-N-C-(X17)-C-N-X-C. Cotransfection assays in heterologous cells demonstrate that GATA-4 trans activates reporter constructs containing GATA promoter elements. Northern (RNA) analysis and in situ hybridization show that GATA-4 mRNA is expressed in the heart, intestinal epithelium, primitive endoderm, and gonads. Retinoic acid-induced differentiation of mouse F9 cells into visceral or parietal endoderm is accompanied by increased expression of GATA-4 mRNA and protein. In vitro differentiation of embryonic stem cells into embryoid bodies is also associated with increased GATA-4 expression. We conclude that GATA-4 is a tissue-specific, retinoic acid-inducible, and developmentally regulated transcription factor. On the basis of its tissue distribution, we speculate that GATA-4 plays a role in gene expression in the heart, intestinal epithelium, primitive endoderm, and gonads.

Amino Acid Sequence↗
PubMed1993

Monoclonal antibody studies on rabies-related viruses.

Rabies and rabies-related viruses are divided into four serotypes, although it has been suggested that the inclusion of European bat lyssaviruses results in six genotypes. Sixty-four rabies-related viruses were tested against a panel of 36 anti-nucleocapsid monoclonal antibodies prepared from the immunization of Balb/c mice with five prototypic rabies-related viruses. Reaction patterns obtained confirmed the original distinction between serotype 1-4 viruses and revealed multiple variants of Lagos bat and Mokola viruses. In addition, two biotypes of European bat lyssavirus were identified and a clear distinction was shown between these biotypes and Duvenhage virus of Africa. The origins and importance of the rabies-related viruses are discussed.

Animals↗
PubMed1993

Canid and viverrid rabies viruses in South Africa.

Historical records suggest that in South Africa rabies was present in viverrids in the early 1800s. In the early 1950s a wave of canine rabies spread from Namibia through Botswana into the northern Transvaal and by 1961 a second front had penetrated south from Mozambique into Swaziland and northern Natal. Today, rabies is regularly confirmed in a number of canid and viverrid species in most regions of South Africa. A panel of anti-nucleoprotein monoclonal antibodies was used to examine 83 virus isolates from these species. Two major reaction patterns, one chiefly confined to viruses from canids and the other to viruses from viverrids, were obtained. In addition, some variation in the reaction patterns of viverrid viruses was observed and spill-over of viverrid virus into canids and vice versa was recorded. Rabies in South Africa appears to behave as two distinct disease entities.

Animals↗