Calculating eGFR using the MDRD equation.
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Creatinine↗
Biomedical subjects
G Miller
Publications and source records attributed to G Miller.
Functional and clinical characterization of a mutation in KCNJ2 associated with Andersen-Tawil syndrome.
BACKGROUND: Andersen-Tawil syndrome (ATS) is a rare inherited disorder, characterised by periodic paralysis, cardiac dysarrhythmias, and dysmorphic features, and is caused by mutations in the gene KCNJ2, which encodes the inward rectifier potassium channel, Kir2.1. This study sought to analyse KCNJ2 in patients with familial ATS and to determine the functional characteristics of the mutated gene. METHODS AND RESULTS: We screened a family with inherited ATS for the mutation in KCNJ2, using direct DNA sequencing. A missense mutation (T75R) of Kir2.1, located in the highly conserved cytoplasmic N-terminal domain, was identified in three affected members of this family. Using the Xenopus oocyte expression system and whole cell voltage clamp analyses, we found that the T75R mutant was non-functional and possessed a strong dominant negative effect when co-expressed with the same amount of wild type Kir2.1. Transgenic (Tg) mice expressing the mutated form of Kir2.1 in the heart had prolonged QTc intervals compared with mice expressing the wild type protein. Ventricular tachyarrhythmias were observed in 5 of 14 T75R-Tg mice compared with 1 of 7 Wt-Tg and none of 6 non-transgenic littermates. In three of five T75R-Tg mice with ventricular tachycardia, their ECG disclosed bidirectional tachycardia as in our proband. CONCLUSIONS: The in vitro studies revealed that the T75R mutant of Kir2.1 had a strong dominant negative effect in the Xenopus oocyte expression system. It still preserved the ability to co-assemble and traffic to the cell membrane in mammalian cells. For in vivo studies, the T75R-Tg mice had bidirectional ventricular tachycardia after induction and longer QT intervals.
Adolescent↗
Gaucher disease in Colombia: mutation identification and comparison to other Hispanic populations.
Gaucher disease is the most common of the lysosomal storage disorders, affecting all ethnic groups. The pathology of this recessively inherited disease arises from the accumulation of glucocerebroside in tissues due to deficient activity of the enzyme glucocerebrosidase (E.C. 3.2.1.45). The glucocerebrosidase (GBA) gene spans a 7.2kb fragment located on locus 1q 21, consisting of 11 exons and 10 introns. Located 16 kb downstream is a highly homologous pseudogene sequence [M. Horowitz, S. Wilder, Z. Horowitz, O. Reiner, T. Gelbart, E. Beutler, The Human Glucocerebrosidase gene and pseudogene: structure and evolution. Genomics 4 (1) (1989) 87-96.]. Fourteen fragments comprising 11 exons of the GBA gene were analyzed in DNA samples from 25 Colombian patients using denaturing High Pressure Liquid Chromatography (DHPLC). Sequencing of abnormal findings led to the discovery of three novel mutations (c.595_596 delCT, c.898 delG and c.1,255 G>C [p.D 419 H] in exons 6, 7, and 9 of the GBA gene) with high prevalence among Colombian patients. We have also found the presence of a double mutation p.L 483 P+p.E 355 K (L 444 P+E 326 K, traditional nomenclature) in two different families classified as Gaucher type 1. This mutation was previously reported in one patient with Gaucher type 2. We have found DHPLC to be a reliable and sensitive method for the detection of mutations and allelic variation in Gaucher patients.
Adolescent↗
Cerebral folate deficiency with developmental delay, autism, and response to folinic acid.
The authors describe a 6-year-old girl with developmental delay, psychomotor regression, seizures, mental retardation, and autistic features associated with low CSF levels of 5-methyltetrahydrofolate, the biologically active form of folates in CSF and blood. Folate and B12 levels were normal in peripheral tissues, suggesting cerebral folate deficiency. Treatment with folinic acid corrected CSF abnormalities and improved motor skills.
Adaptation, Physiological↗
Criticality and universality in a generalized earthquake model.
We propose that an appropriate prototype for modeling self-organized criticality in dissipative systems is a generalized version of the two-variable cellular automata model introduced by Hergarten and Neugebauer [Phys. Rev. E 61, 2382 (2000)]. We show that the model predicts exponents for the event size distribution which are consistent with physically observed results for dissipative phenomena such as earthquakes. In addition we provide evidence that the model is critical based on both scaling analyses and direct observation of the distribution and behavior of the two variables in the interior of the lattice. We further argue that for reasonably large lattices the results are universal for all dissipative choices of the model parameters.
Journal Article↗
The use of the reverse radial fasciosubcutaneous flap to provide soft tissue coverage and a distal recipient artery in a difficult case of toe-to-thumb transfer.
Traumatic amputation of the thumb is a devastating injury. Toe-to-hand [Wei FC, Chen HC, Chuang CC, Chen HT. Microsurgical thumb reconstruction with toe transfer: selection of various techniques. Plast Reconstr Surg 1992;93:345; Wei FC, Tarek AE. Toe-to-hand transfer: current concepts, techniques and research. Clin Plast Surg 1996;23:103] transfer is a sophisticated option for replacing this vital structure, but this challenging procedure, is even more demanding if recipient vessels are difficult to locate, inadequate or even absent. Another frequently encountered difficulty in cases of traumatic thumb amputation is inadequate soft tissue cover in the region of the amputation stump or the first web space. Often this defect or potential defect requires a preliminary tissue transfer procedure, before toe-to-hand transfer can be considered.
Adult↗
SARS Surveillance Project--Internet-enabled multiregion surveillance for rapidly emerging disease.
INTRODUCTION: On March 15, 2003, CDC requested health-care and public health agencies to conduct surveillance for severe acute respiratory syndrome (SARS). The SARS Surveillance Project (SARS-SP) was established to rapidly implement multiregional SARS surveillance in emergency departments (EDs) by using existing Internet-based tools. OBJECTIVES: The objectives of SARS-SP were to 1) disseminate and update SARS screening forms for ED triage, 2) establish surveillance for SARS syndrome elements by using Regional Emergency Medicine Internet (REMI), 3) expand surveillance to multiple regions, and 4) evaluate the usefulness of Internet tools for agile surveillance during a rapidly emerging global epidemic. METHODS: SARS-SP developed, distributed, and updated an Internet-based triage form to identify patients for infection control and public health reporting. EDs then were invited to report visit frequencies with various SARS syndrome elements to local public health authorities by using the REMI Internet application (first in one metropolitan area, and later in four). After pilot-testing in one metropolitan area, the surveillance system was implemented in three others. RESULTS: Active syndromic surveillance was established by health departments in Milwaukee, Wisconsin; Denver, Colorado; Akron, Ohio; and Fort Worth, Texas. A total of 27 EDs reported syndrome frequencies from >146,000 patient encounters. CONCLUSIONS: ED and public health partners reported being satisfied with the system, confirming the usefulness of Internet tools in the rapid establishment of multiregion syndromic surveillance during an emerging global epidemic.
Communicable Diseases, Emerging↗
Practice parameter: diagnostic assessment of the child with cerebral palsy [RETIRED]: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.
OBJECTIVE: The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence. For this parameter the authors reviewed available evidence on the assessment of a child suspected of having cerebral palsy (CP), a nonprogressive disorder of posture or movement due to a lesion of the developing brain. METHODS: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification. RESULTS: CP is a common problem, occurring in about 2 to 2.5 per 1,000 live births. In order to establish that a brain abnormality exists in children with CP that may, in turn, suggest an etiology and prognosis, neuroimaging is recommended with MRI preferred to CT (Level A). Metabolic and genetic studies should not be routinely obtained in the evaluation of the child with CP (Level B). If the clinical history or findings on neuroimaging do not determine a specific structural abnormality or if there are additional and atypical features in the history or clinical examination, metabolic and genetic testing should be considered (Level C). Detection of a brain malformation in a child with CP warrants consideration of an underlying genetic or metabolic etiology. Because the incidence of cerebral infarction is high in children with hemiplegic CP, diagnostic testing for coagulation disorders should be considered (Level B). However, there is insufficient evidence at present to be precise as to what studies should be ordered. An EEG is not recommended unless there are features suggestive of epilepsy or a specific epileptic syndrome (Level A). Because children with CP may have associated deficits of mental retardation, ophthalmologic and hearing impairments, speech and language disorders, and oral-motor dysfunction, screening for these conditions should be part of the initial assessment (Level A). CONCLUSIONS: Neuroimaging results in children with CP are commonly abnormal and may help determine the etiology. Screening for associated conditions is warranted as part of the initial evaluation.
Algorithms↗
Phosphatase activity and populations of microorganisms from cadmium- and lead-contaminated soils.
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Bacteria↗
Human campylobacteriosis in Scotland: seasonality, regional trends and bursts of infection.
Fourier time-series models were constructed to study regional and national seasonality of human campylobacteriosis in Scotland between 1997 and 2001. Strong seasonality was demonstrated with an annual peak of reported cases in late June to early July. The prominence of this peak varied between regions, which was exemplified for the two major population centres: Lothian, with mixed urban/rural population, had a more prominent peak than Greater Glasgow, which has a predominantly urban population. No significant trend of annual cases of campylobacteriosis was found nationally and Fourier models successfully predicted the seasonal pattern of national and regional cases in 2002. During the period studied, the Fourier model identified >20 bursts of infection (potential outbreaks). Multi-regional bursts were also identified in the summers of 1998 and 2000 - the latter comprising the vast majority of the regions in Scotland, which could suggest a national outbreak.
Campylobacter Infections↗
Nonuniversality and scaling breakdown in a nonconservative earthquake model.
We use extensive numerical simulations to test recent claims of universality in the nonconservative regime of the Olami-Feder-Christensen model. By studying larger systems and a wider range of dissipation levels than previously considered we conclude that there is no evidence of universality in the model with only limited regions of the event size distributions displaying power-law behavior. We further analyze the dimension of the largest events in the model, D(max), using a multiscaling method. This reveals that although D(max) initially increases with system size, for larger systems the dimension ultimately decreases with system size casting further doubt on the criticality of the model.
Journal Article↗
Crossover behavior in the event size distribution of the Olami-Feder-Christensen model.
The avalanche size distribution and supercritical toppling value distribution in the Olami-Feder-Christensen model are examined, demonstrating that there exists a crossover value alpha(X) approximately 0.14 for the conservation parameter in the model. We have further confirmed the location of this crossover by identifying upper and lower bounds for alpha(X). For levels of conservation below alpha(X) the asymptotic behavior, in the limit of both infinite-system-size and infinite-precision arithmetic, consists only of avalanches of size 1 with all sites toppling exactly at the threshold value. For larger levels of conservation the probability of finding avalanches of size 2 or bigger remains nonzero in the asymptotic limit.
Journal Article↗
Relative abundance of growth hormone receptor isoforms in rhesus monkey tissues and human transformed lymphocytes.
The growth hormone receptor (GHR) is expressed as one active, full-sequence isoform and one truncated, inactive one that lacks the intracellular signaling domain. The aim of this study was to investigate the variation in the tissue expression of the full and truncated mRNA and protein. Epstein-Barr virus-transformed human B lymphocyte lines were established from 9 normal individuals with a height standard deviation score (SDS) of - 0.1 +/- 1.1 (mean +/- SD). Tissues were also collected from 3 Rhesus monkeys, whose GHR has 94.1 % homology with the human molecule. mRNA quantitation was determined by Real Time Quantitative PCR. Growth hormone receptor expression in transformed lymphocytes was also studied by fluorescence-activated cell sorter analysis. Both isoforms were expressed in transformed lymphocytes, but individual variation in the relative mRNA expression was small (truncated isoform percentage of total receptor mRNA: 17.1 +/- 4.4, mean +/- SD). There was no correlation between donors' height SDS and the expression of either isoform or the ratio between them. Protein expression by FACS analysis showed wider variation among the subjects; however, the relative ratio was similar in all the subjects. In monkey tissues, the truncated receptor showed a tissue-specific distribution. In conclusion, the expression of both isoforms in transformed lymphocytes from normal subjects shows small differences at the RNA or protein levels, and does not correlate with height SDS. Growth hormone splice isoforms show tissue specificity, suggesting local regulation of splicing. Tissues with relatively high expression of the truncated isoform are likely to be more resistant to the effects of GH due to the dominant negative effect of this isoform. In addition, the differential tissue expression might influence the levels of growth hormone binding protein in the immediate milieu of each tissue.
Adult↗
The application of Bayesian techniques in the interpretation of bioassay data.
The inverse problem of internal dosimetry is naturally posed as a problem of Bayesian inference. The Bayesian approach is of practical importance in three areas: (1) avoiding false positives in the detection of rare events, (2) the calculation of uncertainties, and (3) the calculation of multiple intakes, all of which are important for internal dosimetry. In this paper, the Bayesian approach to the interpretation of measurements is first reviewed using a simple conceptual example. Then, a simple 239Pu case using IMBA expert is discussed, and finally a current cutting-edge example is discussed involving real 238Pu data calculated with a Markov Chain Monte Carlo algorithm and with exact calculation of poisson likelihood functions.
Algorithms↗
Review of methods and computer codes for interpretation of bioassay data.
Internal dose determination is an essential component of individual monitoring programmes for workers or members of the public exposed to radionuclides, and methods and computer programs are required for dose assessment. A recent international European Radiation Dosimetry Group (EURADOS) intercomparison has shown unacceptably large ranges in the results assessment. An ICRP working party has been initiated to consider what guidance ICRP can give on the use of models and interpret bioassay data in terms of intake/dose. In this field, six codes for bioassay data interpretation, which implement the current ICRP publication 78 biokinetic models, have been reviewed against several criteria with different levels of importance: minor criteria such as the practical use of the code and the graphical capabilities, and major criteria such as the choice of available parameters, peculiarities of data fitting and interpretation, the choice of biokinetic models and the use of uncertainties. All these criteria were assessed using one artificial set of data and two examples extracted from the previous international EURADOS intercomparison.
Administration, Oral↗
Internal dosimetry of uranium isotopes using Bayesian inference methods.
A group of personnel at Los Alamos National Laboratory is routinely monitored for the presence of uranium isotopes by urine bioassay. Samples are analysed by alpha spectroscopy, and the results are examined for evidence of an intake of uranium. Because the measurement uncertainties are often comparable to the quantities of material we wish to detect, statistical considerations are crucial for the proper interpretation of the data. The problem is further complicated by the significant, but highly non-uniform, presence of uranium in local drinking water and, in some cases, food supply. Software originally developed for internal dosimetry of plutonium has been adapted to the problem of uranium dosimetry. The software uses an unfolding algorithm to calculate an approximate Bayesian solution to the problem of characterising any intakes which may have occurred, given the history of urine bioassay results for each individual in the monitored population. The program uses biokinetic models from ICRP Publications 68 and later, and a prior probability distribution derived empirically from the body of uranium bioassay data collected at Los Alamos over the operating history of the laboratory. For each individual, the software creates a posterior probability distribution of intake quantity and solubility type as a function of time. From this distribution, estimates are made of the cumulative committed dose (CEDE) to each individual. Results of the method are compared with those obtained using an earlier classical (non-Bayesian) algorithm for uranium dosimetry. We also discuss the problem of distinguishing occupational intakes from intake of environmental uranium, within a Bayesian framework.
Algorithms↗
Measurements of criticality in the Olami-Feder-Christensen model.
The Olami-Feder-Christensen model is a simple lattice based cellular automaton model introduced as a prototype to study self-organization in systems with a continuous state variable. Despite its simplicity there remains controversy over whether the system is truly critical in the nonconservative regime. Here we address this issue by introducing the layer branching rate, which measures how contributions to the system branching rate vary across the lattice. By considering this quantity for layers far from the edges of the finite-sized lattices, we find that the model is only critical in the conservative limit, but that previous studies have underestimated the system branching rate in the nonconservative case. We further derive expressions for the branching rate in systems where the state variable across the lattice is described by a uniform distribution, in order to determine the effect of self-organization upon the level of criticality. We find that organization raises the branching rate in the nearest-neighbor case, but in contrast lowers the level of criticality in a random-neighbor model.
Journal Article↗
Chlorohydrocarbon pesticides in the Australian marine environment after banning in the period from the 1970s to 1980s.
The chlorohydrocarbon pesticides (CHPs) (principally DDT, dieldrin, hexachlorocyclohexane (HCH) including lindane, chlordane, heptachlor and heptachlorepoxide, aldrin and hexachlorobenzene (HCB)) were used extensively in Australia during the 1960s and 1970s. These were progressively banned from the 1970s with DDT being totally banned in 1987. The levels in marine waters are believed to have progressively declined as indicated by water in the Brisbane River, which consistently fell from maximum concentrations of about 1.7 microg/l in 1972-1973 to not detectable in 1986-1987. In some urban areas sediment concentrations, up to 1700 microg/kg dry weight, were recorded in the early 1990s which may reflect the reworking and exposure of older more contaminated material. Fish exhibited consistent occurrence of DDT, HCH, dieldrin and HCB through the 1970s to the 1990s. Maximum concentrations of DDT and dieldrin occurred generally in the 1970s at 40.3 and 8.8 microg/g wet weight, and minimums in the 1990s at 2.4 and 0.041 micro/g wet weight respectively. Inputs of dialdrin from sewage and DDT from the broad environment, reflected by the calculated daily human uptake in the diet, were shown to decline with half-lives of 1.1-1.5 and about 3 years respectively. This evidence suggests that banning of the CHPs has greatly reduced the inputs into the marine environment with consequent reductions in concentrations in biota but there is the occasional occurrence of relatively high concentrations.
Animals↗