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Biomedical subjects

D Johnson

Publications and source records attributed to D Johnson.

At least 19 recordsLinked to original sources

The DNA sequence and biological annotation of human chromosome 1.

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

Base Sequence↗

Duplicate publication and 'paper inflation' in the Fractals literature.

The similarity of documents in a large database of published Fractals articles was examined for redundancy. Three different text matching techniques were used on published Abstracts to identify redundancy candidates, and predictions were verified by reading full text versions of the redundancy candidate articles. A small fraction of the total articles in the database was judged to be redundant. This was viewed as a lower limit, because it excluded cases where the concepts remained the same, but the text was altered substantially. Far more pervasive than redundant publications were publications that did not violate the letter of redundancy but rather violated the spirit of redundancy. There appeared to be widespread publication maximization strategies. Studies that resulted in one comprehensive paper decades ago now result in multiple papers that focus on one major problem, but are differentiated by parameter ranges, or other stratifying variables. This 'paper inflation' is due in large part to the increasing use of metrics (publications, patents, citations, etc) to evaluate research performance, and the researchers' motivation to maximize the metrics.

Algorithms↗

Pharmacokinetic parameters of nevirapine and efavirenz in relation to antiretroviral efficacy.

Optimal adherence is essential for successful antiretroviral therapy. We analyzed the relation between minimum plasma drug concentration (Cmin) and total drug exposure over 24 hr (AUC24) with virologic failure for therapy-adherent patients in the nevirapine (NVP) and efavirenz (EFV) groups of the double nonnucleoside study (2NN), which compared the efficacy of NVP and/or EFV together with stavudine and lamivudine. The objective was to find cutoff values of the Cmin and AUC24 below which the risk of virologic failure increased. The relation between Cmin and AUC24 with virologic failure (never a plasma viral load [pVL] < 50 copies/ml or a rebound to two consecutive pVL > 50 copies/ml) was analyzed with proportional hazard analyses. Data were censored at end of study or change of allocated treatment. The risk of virologic failure with NVP (n = 511) started to increase at a Cmin < 3.1 mg/L (hazard ratio [HR], 1.33; 95% confidence interval [CI], 0.89-1.97), but there was no cutoff value below which a statistically significant increased risk occurred. Neither was such a cutoff point identified for the AUC24. The risk of virologic failure with EFV (n = 312) was significantly increased at a Cmin < 1.1 mg/L (HR, 1.95; 95% CI, 1.08-3.54) and an AUC24 < 40 mg x hr x L1 (HR, 1.95; 95% CI, 1.07-3.54). Both cutoff values represent the median values for adherent patients. These associations were driven by patients from Thailand. Adjusting for geographical region made the association between Cmin and AUC24 with virologic failure statistically nonsignificant. The sensitivity of the Cmin values was too low (29% for NVP, 64% for EFV) to be an adequate predictor for virologic failure. We conclude that identifying the Cmin value for the sole purpose of predicting virologic failure in patients who report to be adherent to NVP or EFV is questionable because of the absence of a concentration-response relation (NVP) or the low sensitivity for such a cutoff value (NVP and EFV).

Adult↗

Increased continuity of care associated with decreased hospital care and emergency department visits for patients with asthma.

The objective of this study was to determine the association between continuity of care and emergency room visits/hospital care for patients with asthma. A population-based study was conducted using administrative healthcare datasets obtained from Alberta Health and Wellness, Alberta, Canada. The 4-year study period extended from April 1, 1996 to March 31, 2000, and took place at the Palliser Health Region in Alberta, Canada, which has a population of 88,000 people. A population-based sample of 2774 patients, diagnosed with asthma between ages 5 and 45 with two or more office visits for asthma and who lived in the Palliser Health Region for 2 consecutive years during the study period, was studied. The main outcome measure was the association of continuity of care with hospitalizations and emergency room visits for patients with asthma. Continuity of care was the proportion of total physician visits made to the most frequently visited physician. High continuity of care was associated with a decreased risk of an emergency visit (OR = 0.24: 95% CI 0.19-0.29), number of emergency visits (RR = 0.37; 95% CI 0.32-0.42), decreased risk of number of hospitalizations (RR = 0.69; 95% CI 0.54-0.89), and total days in hospital (average difference = 0.77; 95% CI 0.63-0.95), but not with ever hospitalized. High continuity of care was associated with a 60%-75% reduction in emergency room visits and an approximate 25% reduction in number of hospitalizations in patients with asthma. Interventions to improve continuity of care could have the potential to improve care and reduce cost.

Adolescent↗

Visualisation of needle position using ultrasonography.

Anaesthetists and intensivists spend a considerable proportion of their working time inserting needles and catheters into patients. In order to access deeper structures like central veins and nerves, they have traditionally relied on surface markings to guide the needle into the correct position. However, patients may present challenges due to anatomical abnormalities and size. Irrespective of the skill of the operator, there is the ever-present risk of needle misplacement with the potential of damage to structures like arteries, nerve bundles and pleura. Repeated attempts, even if ultimately successful, cause patient suffering and probably increase the risk of infection and other long term complications. Portable and affordable, high-resolution ultrasound scanners, has accelerated the interest in the use of ultrasound guidance for interventional procedures. Ultrasound guidance offers several advantages including a greater likelihood of success, fewer complications and less time spent on the procedure. Even if the target structure is identified correctly there is still the challenge to place the needle or other devices in the optimum site. The smaller and deeper the target, the greater the challenge and potential usefulness of ultrasound guidance. As a result of limited training in the use of ultrasound we believe that many clinicians fail to use it to its full potential. A lack of understanding, with regard to imaging the location of the needle tip remains a major obstacle. Needle visualisation and related topics form the basis for this review.

Acoustics↗

Current and future water issues in the Oldman River Basin of Alberta, Canada.

Long-term trends in alpine and prairie snow pack accumulation and melt are affecting streamflow within the Oldman River Basin in southern Alberta, Canada. Unchecked rural and urban development also has contributed to changes in water quality, including enhanced microbial populations and increased waterborne pathogen occurrence. In this study we look at changing environment within the Oldman River Basin and its impact on water quality and quantity. The cumulative effects include a decline in net water supplies, and declining quality resulting in increased risk of disease. Our data indicates that decreases in the rate of flow of water can result in sedimentation of bacterial contaminants within the water column. Water for ecosystems, urban consumption, recreation and distribution through irrigation is often drawn from waterholding facilities such as dams and weirs, and concern must be expressed over the potential for contaminate build-up and disproportionate potential of these structures to pose a risk to human and animal health. With disruption of natural flow rates for water resulting from environmental change such as global warming and/or human intervention, increased attention needs to be paid to use of best management practices to protect source water supplies.

Alberta↗

Molecular methods for virus discovery.

The potential use of novel cell substrates from diverse animal species raises concerns about the transmission of hitherto unknown viral agents. Viruses that do not cause a cytopathic effect in cell culture may escape detection by conventional methods and molecular methods may therefore prove useful for screening for hitherto unknown viruses. This review describes currently used molecular methods for virus discovery, including degenerate PCR assays, representational difference analysis and rolling circle amplification, and summarises the advantages and disadvantages of each technique.

Amino Acid Sequence↗

Effect of dislodging techniques on foliar residue determination for agricultural crops.

The Agricultural Reentry Task Force (ARTF) conducted a study to determine whether different dislodgeable foliar residue (DFR) techniques had any effect on the amount of residues dislodged from the leaves of vegetable crops. Four previously employed techniques were evaluated with two chemicals (carbaryl and methomyl) on two crops (cabbage and lettuce). Carbaryl, a moderately water-soluble chemical, was applied at a rate of 2.0 lbs active ingredient/acre (lb ai/A) while methomyl, a highly water soluble chemical, was applied at a rate of 0.9 lb ai/A. One day after application, leaf punches were collected and the residues were dislodged following one of four techniques that differed in the number of dislodgings per sample, the duration of dislodging, the solution volume, and/or the type of solution used. The results indicated that three of the techniques gave similar results, whereas a fourth gave marginally lower results.

Carbaryl↗

Use of in-stream reservoirs to reduce bacterial contamination of rural watersheds.

An investigation into bacterial water quality problems was conducted on an interconnected stream and irrigation system within the Oldman River Basin of southern Alberta, Canada. Levels of indicator bacteria, including fecal coliforms, generic Escherichia coli and fecal streptococci, were repeatedly measured in streams and irrigation return canals of this river basin during the summer of 2001. Bacterial-loading segments of the irrigation/stream system were identified through a comparison of indicator bacteria levels in pairs of upstream and downstream sites. Mann-Whitney U-tests indicated that reservoirs significantly reduced bacterial counts. A temporal comparison of E. coli counts and river discharges suggested that these indicator bacteria do not originate from within in-stream sediments. Site-specific as well as cumulative inputs from a variety of non-point sources are likely to be responsible for the high downstream levels of indicator bacteria in this water system. The use of management practices such as in-stream reservoirs may significantly reduce contamination, and increase the quality of limited rural water supplies to allow their reuse and safe discharge into downstream water sources. The identification of bacteria-loading river/canal segments could also be used to prioritize restoration projects.

Agriculture↗

A temperature-dependent relative-rate study of the OH initiated oxidation of n-butane: the kinetics of the reactions of the 1- and 2-butoxy radicals.

The kinetics of the reactions of 1-and 2-butoxy radicals have been studied using a slow-flow photochemical reactor with GC-FID detection of reactants and products. Branching ratios between decomposition, CH3CH(O*)CH2CH3 --> CH3CHO + C2H5, reaction (7), and reaction with oxygen, CH3CH(O*)CH2CH3+ O2 --> CH3C(O)C2H5+ HO2, reaction (6), for the 2-butoxy radical and between isomerization, CH3CH2CH2CH2O* --> CH2CH2CH2CH2OH, reaction (9), and reaction with oxygen, CH3CH2CH2CH2O* + O2 --> C3H7CHO + HO2, reaction (8), for the 1-butoxy radical were measured as a function of oxygen concentration at atmospheric pressure over the temperature range 250-318 K. Evidence for the formation of a small fraction of chemically activated alkoxy radicals generated from the photolysis of alkyl nitrite precursors and from the exothermic reaction of 2-butyl peroxy radicals with NO was observed. The temperature dependence of the rate constant ratios for a thermalized system is given by k7/k6= 5.4 x 10(26) exp[(-47.4 +/- 2.8 kJ mol(-1))/RT] molecule cm(-3) and k9/k8= 1.98 x 10(23) exp[(-22.6 +/- 3.9 kJ mol(-1))/RT] molecule cm(-3). The results agree well with the available experimental literature data at ambient temperature but the temperature dependence of the rate constant ratios is weaker than in current recommendations.

Butanes↗

Confirmation of CHD7 as a cause of CHARGE association identified by mapping a balanced chromosome translocation in affected monozygotic twins.

BACKGROUND: CHARGE syndrome has an estimated prevalence of 1/10,000. Most cases are sporadic which led to hypotheses of a non-genetic aetiology. However, there was also evidence for a genetic cause with reports of multiplex families with presumed autosomal dominant, possible autosomal recessive inheritance and concordant twin pairs. We identified a monozygotic twin pair with CHARGE syndrome and a de novo balanced chromosome rearrangement t(8;13)(q11.2;q22). METHODS: Fluorescence in situ hybridisation was performed with BAC and PAC probes to characterise the translocation breakpoints. The breakpoint on chromosome 8 was further refined using 10 kb probes we designed and produced using sequence data for clone RP11 33I11, the Primer3 website, and a long range PCR kit. RESULTS: BAC and PAC probe hybridisation redefined the breakpoints to 8q12.2 and 13q31.1. Probe RP11 33I11 spanned the breakpoint on chromosome 8. Using our 10 kb probes we demonstrated that the chromodomain gene CHD7 was disrupted by the translocation between exons 3 and 8. DISCUSSION: Identifying that the translocation breakpoint in our patients occurred between exons 3 and 8 of CHD7 suggests that disruption of this gene is the cause of CHARGE syndrome in the twins and independently confirms the role of CHD7 in CHARGE syndrome.

Abnormalities, Multiple↗

Distinct phenotype associated with a cryptic subtelomeric deletion of 19p13.3-pter.

Telomeres are gene rich regions with a high recombination rate. Cryptic subtelomeric rearrangements are estimated to account for 5% of mental retardation/malformation syndromes. Here we present the first patient with a deletion of 19p13.3, identified by subtelomeric FISH analysis. His features included a distinctive facial appearance, cleft palate, hearing impairment, congenital heart malformation, keloid scarring, immune dysregulation, and mild learning difficulties. Subtelomeric FISH analysis identified a deletion of 19p13.3-pter. The deletion size was determined to be 1.2 Mb by FISH analysis. It extended from within the chromosomal region covered by BAC RP11-50C6 to 19pter. The deleted area encompassed approximately 60 genes. Fifteen possible candidate genes were considered with respect to the phenotype, including follistatin-related precursor 3 (FSTL3) and serine-threonine kinase 11 (STK-11).

Abnormalities, Multiple↗

The genome of the social amoeba Dictyostelium discoideum.

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

ATP-Binding Cassette Transporters↗

Characteristics and scaling of tungsten-wire-array z -pinch implosion dynamics at 20 MA.

We present observations for 20-MA wire-array z pinches of an extended wire ablation period of 57%+/-3% of the stagnation time of the array and non-thin-shell implosion trajectories. These experiments were performed with 20-mm-diam wire arrays used for the double- z -pinch inertial confinement fusion experiments [M. E. Cuneo, Phys. Rev. Lett. 88, 215004 (2002)] on the Z accelerator [R. B. Spielman, Phys. Plasmas 5, 2105 (1998)]. This array has the smallest wire-wire gaps typically used at 20 MA (209 microm ). The extended ablation period for this array indicates that two-dimensional (r-z) thin-shell implosion models that implicitly assume wire ablation and wire-to-wire merger into a shell on a rapid time scale compared to wire acceleration are fundamentally incorrect or incomplete for high-wire-number, massive (>2 mg/cm) , single, tungsten wire arrays. In contrast to earlier work where the wire array accelerated from its initial position at approximately 80% of the stagnation time, our results show that very late acceleration is not a universal aspect of wire array implosions. We also varied the ablation period between 46%+/-2% and 71%+/-3% of the stagnation time, for the first time, by scaling the array diameter between 40 mm (at a wire-wire gap of 524 mum ) and 12 mm (at a wire-wire gap of 209 microm ), at a constant stagnation time of 100+/-6 ns . The deviation of the wire-array trajectory from that of a thin shell scales inversely with the ablation rate per unit mass: f(m) proportional[dm(ablate)/dt]/m(array). The convergence ratio of the effective position of the current at peak x-ray power is approximately 3.6+/-0.6:1 , much less than the > or = 10:1 typically inferred from x-ray pinhole camera measurements of the brightest emitting regions on axis, at peak x-ray power. The trailing mass at the array edge early in the implosion appears to produce wings on the pinch mass profile at stagnation that reduces the rate of compression of the pinch. The observation of precursor pinch formation, trailing mass, and trailing current indicates that all the mass and current do not assemble simultaneously on axis. Precursor and trailing implosions appear to impact the efficiency of the conversion of current (driver energy) to x rays. An instability with the character of an m = 0 sausage grows rapidly on axis at stagnation, during the rise time of pinch power. Just after peak power, a mild m = 1 kink instability of the pinch occurs which is correlated with the higher compression ratio of the pinch after peak power and the decrease of the power pulse. Understanding these three-dimensional, discrete-wire implosion characteristics is critical in order to efficiently scale wire arrays to higher currents and powers for fusion applications.

Journal Article↗

Effects of increased deposition of atmospheric nitrogen on an upland Calluna moor: N and P transformations.

This study determined the effects of increased N deposition on rates of N and P transformations in an upland moor. The litter layer and the surface of the organic Oh horizon were taken from plots that had received long-term additions of ammonium nitrate at rates of 40, 80 and 120 kg N ha(-1) yr(-1). Net mineralisation processes were measured in both field and laboratory incubations. Soil phosphomonoesterase (PME) activity and rates of N(2)O release were measured in laboratory incubations and root-surface PME activity measured in laboratory microcosms using Calluna vulgaris bioassay seedlings. Net mineralisation rates were relatively slow, with net ammonification consistently stimulated by N addition. Net nitrification was marginally stimulated by N addition in the laboratory incubation. N additions also increased soil and root-surface (PME) activity and rates of N(2)O release. Linear correlations were found between litter C:N ratio and all the above processes except net nitrification in field incubations. When compared with data from a survey of European forest sites, values of litter C:N ratio were greater than a threshold below which substantial, N input-related increases in net nitrification rates occurred. The maintenance of high C:N ratios with negligible rates of net nitrification was associated with the common presence of ericaceous litter and a mor humus layer in both this moorland as well as the forest sites.

Air Pollutants↗

Chronomics of autism and suicide.

We examine whether autism may be influenced by non-photic environmental factors, among others, in a California database consisting of the number of cases added quarterly to the system between 1993 and 2004. Instead of a precise calendar (1.0)-year-long spectral component, we detect unseen primarily helio- and geomagnetic signatures, including a newly discovered near-transyear of 1.09-year length. In this case, it overrides any undetected seasonal effects, the topic of much previous unrewarding research, also analyzed herein without overcoming the limitation by stacking. Since we could not get additional data on autism, data on suicides, the final "detachment" and failure to bond, were also analyzed, again revealing a spectrum of non-photic signatures. What we do not see and do not anticipate can exist and can override the seasons, as resolved time-microscopically by chronomics, the study of chronomes (time structures). Just as spatial microscopy and electron microscopy resolved infectious agents, so does microscopy in time resolve the signature of environmental agents in human behavior in health and disease.

Autistic Disorder↗

Molecular screening for microdeletions at 9p22-p24 and 11q23-q24 in a large cohort of patients with trigonocephaly.

Trigonocephaly is a rare form of craniosynostosis characterized by the premature closure of the metopic suture. To contribute to a better understanding of the genetic basis of metopic synostosis and in an attempt to restrict the candidate regions related to metopic suture fusion, we studied 76 unrelated patients with syndromic and non-syndromic trigonocephaly. We found a larger proportion of syndromic cases in our population and the ratio of affected male to female was 1.8 : 1 and 5 : 1 in the non-syndromic and syndromic groups, respectively. A microdeletion screening at 9p22-p24 and 11q23-q24 was carried out for all patients and deletions in seven of them were detected, corresponding to 19.4% of all syndromic cases. Deletions were not found in non-syndromic patients. We suggest that a molecular screening for microdeletions at 9p22-p24 and 11q23-q24 should be offered to all syndromic cases with an apparently normal karyotype because it can potentially elucidate the cause of trigonocephaly in this subset of patients. We also suggest that genes on the X-chromosome play a major role in syndromic trigonocephaly.

Child↗