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Results for “Observer Variation”

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PubMed1999

Hepatitis C virus RNA profiles in chronically infected individuals: do they relate to disease activity?

Fluctuations of hepatitis C virus (HCV)-RNA serum levels were monitored in a multicenter study in 76 chronic HCV carriers who had been followed longitudinally without receiving antiviral therapy to assess their relation with the course of liver disease activity. Forty-four patients had normal transaminases over more than 2 years, while 32 additional patients had fluctuating levels. Viral load was measured in serial serum samples prospectively collected for 10 to 12 months in 54 patients and in sera stored yearly up to 8 years in an additional 22 patients. In patients tested monthly, a lesser extent of fluctuations was detected in cases with constantly normal transaminases as compared with those with fluctuating transaminases. In the former group, the mean difference between maximum and minimum values observed in each individual patient was 0.7 Log, while in the latter group, it was 1.3 Log (P =.0004). Most of these patients experienced, on average, three peaks of viremia over 1 year. The range of variation observed upon yearly testing was between 0.2 and 2.2 Log and did not reach statistical significance between the two groups. In conclusion, a careful viral replication profile can be achieved only by monthly testing, because longer time intervals could miss viremia fluctuations. HCV-RNA levels are more stable in asymptomatic HCV carriers than in patients with biochemical activity of liver disease.

Adult↗

PubMed2003

Cytochrome P4502E1 (CYP2E1) expression in peripheral blood lymphocytes: evaluation in hepatitis C and diabetes.

OBJECTIVE: Cytochrome P4502E1 (CYP2E1) is expressed in human peripheral blood lymphocytes (PBLs), and previous reports have suggested the possibility of using this readily available tissue as a reporter of CYP2E1 status. To further explore the relevance of this approach we assessed CYP2E1 expression in PBLs in two contrasting conditions, chronic hepatitis C and insulin-dependent diabetes (IDD), illustrating an organ and a systemic disease, respectively. METHODS: Total RNA was isolated from extracted PBLs (hepatitis C patients + IDD) and by percutaneous needle biopsy (hepatitis C patients only). Gene expression for CYP2E1 was determined by real-time reverse-transcription polymerase chain reaction. Histological changes in liver tissue were assessed according to Ludwig's criteria. RESULTS: In patients with chronic hepatitis C a clear relationship was found between CYP2E1 expression in the liver and the progression of hepatic disease (both lobular inflammation and fibrosis indices), and observed variations were consistent with the preferential distribution of CYP2E1 in the lobular zone. No effect of the liver disease was, however, found at the PBL level. A statistically significant increase in mean CYP2E1 expression level was observed in the lymphocytes from poorly controlled IDD subjects compared to controls. CONCLUSIONS: Taken together, our data indicate that the measurement of CYP2E1 expression in PBLs is not useful in liver diseases. However, in a systemic condition (IDD) this measurement can be proposed for monitoring the CYP2E1 induction in a relatively noninvasive manner. This tool should therefore be further validated in clinical field or experimental studies for CYP2E1 phenotyping purposes.

Case-Control Studies↗

PubMed1991

Secondary structure as a constraint on the evolution of a plant viral satellite RNA.

The genetic variability and evolution of the satellite RNA (satRNA) of cucumber mosaic virus (CMV) was analyzed. Twenty-five CMV-satRNAs compared clustered into three main groups, and no correlation was found between genetic proximity and other characteristics (pathogenicity, geographical origin) of the satRNAs. Values for the number of nucleotide substitutions per site between any two satRNAs suggest that divergence is checked by functional constraints. The analysis of mutations relative to an ancestral sequence, and the number of substitutions per site at first, second and third positions of codons in putative open reading frames, show that the variation of CMV-satRNAs does not follow a pattern typical of coding sequences, and indicates that preservation of the sequence of encoded products is not a constraint to evolution. On the other hand, when the observed variation was analyzed relative to a secondary structure model proposed for CMV-satRNAs, several lines of evidence indicated that the maintenance of the secondary structure is a constraint to evolution: the number of substitutions per site, the number of point insertions and deletions and the number of base substitutions that would disrupt base-pairing were significantly higher for unpaired than for base-paired positions. Also, compensatory mutations at base-paired positions occurred more frequently than expected from random. The results suggest that CMV-satRNAs are non-coding, functional RNAs whose biology would be determined by their direct interaction with components of the host and/or the helper virus.

Base Composition↗

PubMed2002

Variation among Escherichia coli O157:H7 strains relative to their growth, survival, thermal inactivation, and toxin production in broth.

To estimate the potential outcomes of food processing on the fate of foodborne pathogens. variations in microbial parameters such as growth rate, survival time, thermal inactivation time, and toxin production must be known. Previous microbial studies using single strains or cocktails provide error estimates for the uncertainty of the experimental and statistical procedures, but not for variations among strains. In this study, the behavior of 17 strains of Escherichia coli O157:H7 were followed when placed in synthetic media that permitted growth, survival, or thermal inactivation. The parameter values were not rejected as being normal, lognormal, gamma, or Weibull distributions. The ratio of the standard deviation to mean (normal distribution) for the exponential growth rate was 0.16 and for the lag phase duration, it was 0.38. The ratios of times to achieve a 4-log10 reduction at two survival conditions were 0.39 and 0.46; ratios of thermal D values at 55 and 60 degrees C were 0.42 and 0.33, respectively. The ratio of the negative log10 of toxin production was 0.24. These distributions are larger than the coefficient of variations observed for experimental errors in single strain and cocktail experiments. This indicates the limitations in precision that predictions of future population numbers can have when the potential presence of all strains needs to be considered. This variation among strains is applicable whether predictions are made by traditional subjective and point estimates or by using models and risk assessments.

Bacterial Toxins↗

PubMed1988

Origins and organization of genetic diversity in natural populations of Trypanosoma brucei.

Experimental work has established that a sexual process can occur in African trypanosomes (Jenni, Marti, Schweizer, Betschart, Le Page, Wells, Tait, Paindavoine, Pays & Steinert, 1986; Paindavoine, Zampetti-Bosseler, Pays, Schweizer, Guyaux, Jenni & Steinert, 1986; Tait, personal communication). However, the role of the process in natural populations of trypanosomes is poorly understood. This paper considers what information can be gained from analyses of isoenzyme polymorphism. A cladistic approach is used to help determine whether trypanosome diversity could have been produced by mutation alone. When applied to three East African populations of Trypanosoma brucei it provides evidence that some diversity has arisen through a sexual process; this explains the variation observed within a locality and can account for the evolution of differences between localities. However, the extent to which genetic exchange currently operates is less clear. Analysis of genotype frequencies indicates that agreements with Hardy-Weinberg expectations can be obtained even if genetic exchange exerted no influence over genotype frequencies. Moreover, analysis of joint locus frequencies reveals disequilibrium between loci and that trypanosome populations may be lacking several genotype combinations. Thus, genetic exchange may not occur sufficiently frequently, or in such a way as to break up associations between loci. The relevance of these observations to the evolution of strain differences within T. brucei is discussed.

Alleles↗

PubMed2005

Effects of dissolved organic carbon on phosphate retention on two calcareous soils.

To evaluate the effects of dissolved organic carbon (DOC) on phosphate retention (including both sorption and/or precipitation reactions) on soils, experiments were performed by using two typical calcareous soils from southeastern Spain (Calcic Regosol and Luvic Xerosol) and two different types of DOC: (1) extracts from a commercial peat (DOC-PE) and (2) high-purity tannic acid (DOC-TA). The experiments were carried out from a 0.01 M CaCl2 aqueous medium at 25 degrees C. The results obtained show that the presence of both DOC-PE and DOC-TA, over a concentration range of 15 (DOC-15) to 100 (DOC-100) mg L(-1), produces in all cases a decreasing amount of phosphate retained in the soils studied, the decrease observed being higher when DOC-PE is used as source of DOC. The values of the decrease observed when DOC-PE was added ranged between 19.9% (DOC-15) and 15.6% (DOC-100) for the Calcic Regosol and between 17.3% (DOC-70, DOC-100) and 14.6% (DOC-15) for the Luvic Xerosol. The variation observed when DOC-TA was added ranged between 8.5% (DOC-100) and 0.5% (DOC-35) for the Calcic Regosol and between 7.0% (DOC-100) and 1.0% (DOC-15) for the Luvic Xerosol.

Adsorption↗

PubMed1998

Protein F, a fibronectin-binding protein of Streptococcus pyogenes, also binds human fibrinogen: isolation of the protein and mapping of the binding region.

During screening of a gene library of Streptococcus pyogenes type M15 for fibrinogen-binding material, a protein of approximately 100 kDa, encoded outside the vir region, was found. DNA sequencing revealed this component to be identical to protein F, a fibronectin-binding protein. Isolation of the recombinant protein, termed F15, was performed by the use of fibrinogen affinity chromatography. The affinity constant (Ka) of protein F15 for fibrinogen, 1.25 x 10(7) mol-1, was lower than that for fibronectin, 1.8 x 10(8) mol-1. The fibrinogen-binding domain was located in the N-terminal part of the molecule, while the fibronectin-binding domains, as previously determined, were in the C-terminal portion of protein F. To examine the amino acid sequence heterogeneity of protein F, the 5' part of the prtF gene, corresponding to the N-terminal variable region of the protein, was amplified by PCR from 12 strains of S. pyogenes belonging to six different M-types. Alignment of these nucleotide sequences indicated that the 5' portion of the prtF gene had probably undergone a number of intragenic recombination and horizontal gene transfer events, allowing a pattern of structural diversity of protein F observed earlier for some other streptococcal virulence factors. There was no strict correlation between M-type and nucleotide sequence of the variable region of the prtF gene and, compared to streptococcal M protein, the overall variation observed for protein F appeared more limited.

Adhesins, Bacterial↗

PubMed2001

How surgeon age affects post-treatment surveillance strategies for melanoma patients.

The intensity of post-treatment melanoma patient follow-up varies widely among physicians. We investigated whether physician age accounts for the observed variation in surveillance intensity among plastic surgeons. A custom-designed questionnaire was mailed to USA and non-USA surgeons, all of whom were members of the American Society of Plastic and Reconstructive Surgeons. Subjects were asked how they use 14 specific follow-up modalities during years 1-5 and 10 following primary treatment for patients with cutaneous melanoma. Repeated-measures analysis of variance was used to compare practice patterns by TNM stage, year post-surgery, and age. Of the 3,032 questionnaires mailed, 1,142 (38%) were returned. Of those returned, 395 (35%) were evaluable. Non-evaluability was usually due to lack of melanoma patient follow-up in surgeons' practices. Follow-up strategies for most of the 14 modalities were highly correlated across TNM stages and years post-surgery, as expected. The pattern of testing varied significantly by surgeon age for 3 modalities (complete blood count, liver function tests, and chest X-ray), but the variation was quite small. We concluded that the post-treatment surveillance practice patterns of ASPRS members caring for patients with cutaneous melanoma vary only marginally with physician age. Continuing medical education could account for this observation.

Adult↗

PubMed2003

Males influence maternal effects that promote sexual selection: a quantitative genetic experiment with dung beetles Onthophagus taurus.

Recently, doubt has been cast on studies supporting good genes sexual selection by the suggestion that observed genetic benefits for offspring may be confounded by differential maternal allocation. In traditional analyses, observed genetic sire effects on offspring phenotype may result from females allocating more resources to the offspring of attractive males. However, maternal effects such as differential allocation may represent a mechanism promoting genetic sire effects, rather than an alternative to them. Here we report results from an experiment on the horned dung beetle Onthophagus taurus, in which we directly compare genetic sire effects with maternal effects that are dependent on sire phenotype. We found strong evidence that mothers provide more resources to offspring when mated with large-horned males. There were significant heritabilities for both horn length and body size, but when differential maternal effects were controlled, the observed estimates of genetic variance were greatly reduced. Our experiment provides evidence that differential maternal effects may amplify genetic effects on offspring traits that are closely related to fitness. Thus, our results may partly explain the relatively high coefficients of additive genetic variation observed in fitness-related traits and provide empirical support for the theoretical argument that maternal effects can play an important role in evolution.

Animals↗

PubMed1995

Measuring the contribution of randomness, exposure, weather, and daylight to the variation in road accident counts.

Road accident counts are influenced by random variation as well as by various systematic, causal factors. To study these issues, a four-country, segmented data base has been compiled, each segment consisting of monthly accident counts, along with candidate explanatory factors, in the various counties (provinces) of Denmark, Finland, Norway, or Sweden. Using a generalized Poisson regression model, we are able to decompose the variation in accident counts into parts attributable to randomness, exposure, weather, daylight, or changing reporting routines and speed limits. To this purpose, a set of specialized goodness-of-fit measures have been developed, taking explicit account of the inevitable amount of random variation that would be present in any set of accident counts, no matter how well known the accident generating Poisson process. Pure randomness is seen to "explain" a major part of the variation in smaller accident counts (e.g. fatal accidents per county per month), while exposure is the dominant systematic determinant. The relationship between exposure and injury accidents appears to be almost proportional, while it is less than proportional in the case of fatal accidents or death victims. Together, randomness and exposure account for 80% to 90% of the observable variation in our data sets. A surprisingly large share of the variation in road casualty counts is thus explicable in terms of factors not ordinarily within the realm of traffic safety policy. In view of this observation, it may seem unlikely that very substantial reductions in the accident toll can be achieved without a decrease in the one most important systematic determinant: the traffic volume.

Accidents, Traffic↗

PubMed1989

Acute nonlymphocytic leukemias of childhood. Inter-observer variability and problems in the use of the FAB classification.

The French-American-British (FAB) classification system and some recent modifications were applied to 486 children with a diagnosis of acute nonlymphocytic leukemia (ANLL) to determine the distribution of the subtypes in children, to document the extent of inter-observer variation in assigning subtypes, and to examine the reasons for the differences. The distribution of FAB subtypes of childhood ANLL was similar to that reported for adults. In the initial year of the study, the inter-observer concurrence between the institutional diagnosis and the reviewing pathologists was 50%, but in the more recent years, concurrence between institutions and the review pathologist has approached 80%, averaging around 73% for the entire study. Many problems remain to be solved with this classification system, including the imprecision in wording, the subjectiveness of the interpretation, errors due to the random distribution of cells, and the current lack of evidence that certain FAB subtypes, such as M1 and M2, differ significantly in terms of biological behavior and prognosis.

Adolescent↗

PubMed1996

Variation in purchasing for the invasive management of coronary heart disease.

This paper reports the results of a postal questionnaire survey of Directors of Public Health in all health authorities in the United Kingdom (as at March 1994). Our aim was to examine variations in the purchasing of coronary artery bypass grafting, percutaneous transluminal coronary angioplasty and coronary angiography. Information on planned service developments in cardiology was also sought. The response rate was 62%. The mean rate of CABG was 374 per million total population (range 162-710); PTCA 183 (range: 18-648); and coronary angiography 1,010 (range 581-2,334). The mean ratio of invasive treatment to angiography was 1:2 Variations in provision were not related to mortality from coronary heart disease or the availability of a local provider. Those districts purchasing higher levels of CABG tended to purchase higher levels of PTCA (Spearman's r = 0.52). Observed variations in purchasing of invasive treatments and investigation for coronary heart disease do not relate to population "need' as defined by mortality rates from CHD. The greatest variations are seen in the purchasing of PTCA, an intervention whose place in the management of CHD is as yet not fully defined. Consensus guidelines on the appropriate use of these interventions and on population needs are required.

Angioplasty, Balloon, Coronary↗

PubMedDate not supplied

Influence of season and anaesthetic on cutaneous vascular permeability responses to histamine, serotonin and mast cell-releasing agents in rats.

The influences of season and anaesthetic on the cutaneous vascular permeability responses to histamine (2.5 X 10(-8) mol), serotonin (5HT, 2.5 X 10(-10) mol), and to the mast cell-releasing agents adenosine 5(1)-triphosphate (2.5 X 10(-7) mol), dextran (5 X 10(-5) g) and compound 48/80 (1 X 10(-7) g) were examined using an Evans blue dye leakage technique. In rats anaesthetized with urethane (1 g/kg i.p.), responses to irritants were significantly less than in rats given ether for the period of administration of irritants and allowed to recover consciousness. The response to histamine was mediated by H1-receptors since it was abolished by mepyramine but not by metiamide. The only seasonal variation observed was in responses to 5HT in urethane-anaesthetized rats, which were significantly less in winter than in summer. It was concluded that dye leakage responses to irritants are affected more by anaesthetic than by seasonal variation.

Anesthesia↗

PubMed1991

Histoplasma variation and adaptive strategies for parasitism: new perspectives on histoplasmosis.

This review summarizes the biology of Histoplasma capsulatum in relation to a wide variety of corresponding pathologies in histoplasmosis. Features of these disease syndromes can be explained in part by natural variations within the fungal population and adaptations made by individual organisms to specific environments. H. capsulatum grows as mycelia and conidia in the soil; once inhaled, the organism undergoes a dramatic morphological and physiological conversion to a yeast form. The yeasts proliferate within the phagolysosomes of macrophages, using a variety of specific strategies for intracellular survival. Even avirulent strains or variants are able to avoid being killed by macrophages and instead establish inapparent or persistent infections. The ingested avirulent organisms assume enlarged shapes similar in appearance to those seen in histological sections of tissues from patients with histoplasmosis. Respiratory tract epithelial cells also appear to play a role in persistence: within them yeasts undergo phenotypic switching akin to the phase variation observed in other pathogens. This particular change involves the loss or modification of cell wall alpha-(1,3)-glucan, which is also correlated with the spontaneous appearance of avirulent variants. The repertoire of adaptive responses and natural variations within this species probably evolved from the need to adjust to a wide range of dynamic environments. In combination with the immune status of the host, these characteristics of H. capsulatum appear to influence the epidemiology, extent, and persistence of histoplasmosis.

Animals↗

PubMed2006

Global patterns in human mitochondrial DNA and Y-chromosome variation caused by spatial instability of the local cultural processes.

Because of the widespread phenomenon of patrilocality, it is hypothesized that Y-chromosome variants tend to be more localized geographically than those of mitochondrial DNA (mtDNA). Empirical evidence confirmatory to this hypothesis was subsequently provided among certain patrilocal and matrilocal groups of Thailand, which conforms to the isolation by distance mode of gene diffusion. However, we expect intuitively that the patterns of genetic variability may not be consistent with the above hypothesis among populations with different social norms governing the institution of marriage, particularly among those that adhere to strict endogamy rules. We test the universality of this hypothesis by analyzing Y-chromosome and mtDNA data in three different sets of Indian populations that follow endogamy rules to varying degrees. Our analysis of the Indian patrilocal and the matrilocal groups is not confirmatory to the sex-specific variation observed among the tribes of Thailand. Our results indicate spatial instability of the impact of different cultural processes on the genetic variability, resulting in the lack of universality of the hypothesized pattern of greater Y-chromosome variation when compared to that of mtDNA among the patrilocal populations.

Chromosome Mapping↗

PubMed1990

Kinetics of the formation and removal of cisplatin-DNA adducts in blood cells and tumor tissue of cancer patients receiving chemotherapy: comparison with in vitro adduct formation.

During chemotherapy with a cisplatin-containing combination of drugs, 217 blood samples from 30 cancer patients were analyzed for the presence of the main cisplatin-DNA adduct cis-Pt(NH3)2d(pGpG) (Pt-GG). Cisplatin was administered during 3-h infusions on each of 5 consecutive days, resulting in increasing adduct levels which, on the average, were about twice as high after the fifth as after the first infusion. Higher levels were found in blood samples of patients who received the same total amount of cisplatin in one single 3-h infusion. No significant differences in adduct levels were found during first and repeated courses. The nonlinear dependence of adduct levels on total dose can be attributed to removal of adducts. At 21 h after a very first cisplatin infusion 76% of the adducts were removed. Lower percentages of removal were observed over the 21-h periods following the fourth and fifth infusions of 5-day courses (49 and 53%, respectively). After the initial 21 h the removal of adducts continued, albeit at a slower rate. Substantial interindividual variation was found in the adduct levels, which did correlate with the levels obtained after in vitro cisplatin treatment of blood samples from the same patients but not with their age or gender. Testicular cancer patients with complete tumor response showed higher adduct levels in their blood than those with partial response or progressive disease. When blood samples from 8 healthy volunteers were treated with cisplatin in vitro, the person-to-person variation in adduct levels and the intraindividual variation observed over a 2-year period were found to be in the same range, which was narrower than that observed with samples from treated patients. In vitro studies with human blood showed that the formation of the Pt-GG adduct is proportional to cisplatin concentration and complete after about 1 hour. In some of the in vivo and in vitro cisplatin-treated blood samples, all 4 known platinum-DNA adducts were determined. In all cases Pt-GG was by far the major adduct, and no significant differences were observed with respect to the relative amounts of the 4 adducts. Similar adduct ratios were found in DNA from a testicular tumor obtained from a patient who underwent orchidectomy; the Pt-GG adduct level was about 10-fold higher than that in his blood cells.

Adult↗

PubMed2005

Phylogeography of Mabuya maculilabris (Reptilia) from São Tomé Island (Gulf of Guinea) inferred from mtDNA sequences.

The pattern of genetic variation of the lizard Mabuya maculilabris from São Tomé Island (Gulf of Guinea) was investigated using a combination of three mitochondrial DNA gene fragments. Forty-eight haplotypes were recovered among 66 individuals covering the whole island. The genealogy inferred from the most parsimonious network of haplotypes allows us to detect two main and long branches departing from the putative group of oldest haplotypes. The tips of these branches exhibit star-like phylogenies, which may indicate of recently expanded populations, most probably from a small number of founders. A nested clade analysis suggests a complex pattern of past events that gave rise to the extant geographical pattern found in the haplotype distribution: past and allopatric fragmentation, range expansion, restricted gene flow and long-distance dispersal. These results are consistent with the complex geological history of the island where important volcanic activity with extensive lava flows has occurred during several periods. Mismatch-distribution analysis and AMOVA also support these conclusions. Substantial genetic structuring among these lizards was detected as well as high levels of differentiation between the southern edge populations (particularly those from the Rolas Islet) and the remaining ones. However, variation is low relative to the geological age of the island. Our results indicate that patterns of variation observed in reptiles in other oceanic islands are not indicative of those observed in the islands of the Gulf of Guinea.

Animals↗

PubMed1975

Ontogeny of spontaneous locomotor activity in rabbit, rat, and guinea pig.

Postnatal locomotor activity was investigated in rabbit, rat, and guinea pig. A peak was found in this behavior at 5 days of age in the rabbit and, in confirmation of earlier studies, at 15-20 days in the rat. Neonatal guinea pigs showed no variation in activity levels due to age. The guinea pig is born at an advanced stage of neural maturation in comparison with the rat, and the rabbit is born at an intermediate stage. This difference accounts for the observed variations in postnatal activity profiles if it is assumed that the behavioral peak coincides with the transition from a stage of primarily mesencephalic arousal system maturation to a stage of primarily diencephalic and telencephalic inhibitory system maturation.

Age Factors↗