Identification and typing of Francisella tularensis with a highly automated genotyping assay.

A PCR assay was developed to genotypically characterize Francisella tularensis and F. novicida. An integrated and partially redundant set of markers was selected to provide positive identification of these species, identify subspecies of F. tularensis and genotype 14 variable number tandem repeat (VNTR) markers. Assay performance was evaluated with 117 Francisella samples. Sample DNA was amplified, and the masses of the PCR products were determined with electrospray ionization/time of flight mass spectrometry (ESI-MS). The base compositions of the PCR amplicons were derived from these high-accuracy mass measurements and contrasted with databased information associated with each of the 25 assay markers. Species and subspecies determinations for all samples were fully concordant with results from established typing methods, and VNTR markers provided additional discrimination among samples. Sequence variants were observed with a number of assay markers, but these did not interfere with sample characterization, and served to increase the genetic diversity detected by the assay.

Hidden Variation in Microsatellite Loci: Utility and Implications for Forensic DNA Analysis.

Short tandem repeat (STR) analysis has been the standard in forensic DNA examinations for almost 15 years. The purpose of this article is to provide some perspective on the biological nature of STR alleles themselves, examine underlying distributions of alleles in the STR loci that are routinely used, and to discuss features of these alleles that are not observable with the currently employed methods. Many of the internationally standardized STR loci contain variations of their interrupted repeat structures, either due to the compound or complex nature of the locus or due to nucleotide variations within the simple repeat motif, which inevitably leads them to become more stratified at the population level. Current STR typing procedures utilizing PCR amplification followed by fragment analysis via capillary or gel electrophoresis does not provide the resolution to discern these polymorphisms. Thus, current designation of alleles is operationally and not biologically defined. Although in the comparison of an evidentiary STR profile to that of a potential contributor, the biological nature of the allele may not be of consequence. When comparisons require assumptions of relatedness between individuals, the biological nature of shared alleles becomes an underlying focus. Herein we will discuss the nature of these additional allelic polymorphisms, what is known of their distribution among the STR loci utilized in forensic testing and within populations, and the advantages this level of allelic discrimination has in forensic and relationship testing.

Fast-electron transport and heating of solid targets in high-intensity laser interactions measured by K alpha fluorescence.

We present experimental results on fast-electron energy deposition into solid targets in ultrahigh intensity laser-matter interaction. X-ray K alpha emission spectroscopy with absolute photon counting served to diagnose fast-electron propagation in multilayered targets. Target heating was measured from ionization-shifted K alpha emission. Data show a 200 microm fast-electron range in solid Al. The relative intensities of spectrally shifted Al K alpha lines imply a mean temperature of a few tens of eV up to a 100 microm depth. Experimental results suggest refluxing of the electron beam at target rear side. They were compared with the predictions of both a collisional Monte Carlo and a collisional-electromagnetic, particle-fluid transport code. The validity of the code modeling of heating in such highly transient conditions is discussed.

Non-arteritic anterior ischaemic optic neuropathy and the treatment of erectile dysfunction.

AIM: To determine the association between Viagra (sildenafil) and Cialis (tadalafil) and non-arteritic anterior ischaemic optic neuropathy (NAION). METHODS: A retrospective matched case-control study was conducted. 38 cases of NAION in males were identified from an academic ophthalmology practice in Birmingham, Alabama, and matched (on age) to 38 controls without a history of NAION. Self reported information regarding past and current use of Viagra and/or Cialis was obtained via a telephone questionnaire from interviewers who were not blind to case status. RESULTS: Overall, males with NAION were no more likely to report a history of Viagra or Cialis use compared to similarly aged controls (odd ratio (OR) 1.75, 95% confidence interval (CI) 0.48 to 6.30 and OR 1.82, 95% CI 0.21 to 15.39). However, for those with a history of myocardial infarction, a statistically significant association was observed (OR 10.7, 95% CI 1.3 to 95.8). A similar association was observed for those with a history of hypertension though it lacked statistical significance (OR 6.9, 95% CI 0.8 to 63.6). CONCLUSIONS: For men with a history of myocardial infarction or hypertension the use of Viagra or Cialis may increase the risk of NAION. Physicians prescribing these medications to patients with these conditions should warn them about the potential risk of NAION.

The relation between C reactive protein and age related macular degeneration in the Cardiovascular Health Study.

AIM: To test the hypothesis that individuals with age related macular degeneration (AMD) have increased C reactive protein (CRP) levels. METHODS: A cross sectional study design using data from the Cardiovascular Health Study (CHS), a longitudinal study that enrolled older adults from four communities in the United States from 1989 to 1990, was employed to investigate the existence of an association between AMD and CRP levels in this population. Fundus photographs from 1997 and 1998 were used to identify individuals with (n=390) and without AMD (n=2365). The association between AMD and CRP levels (measured at baseline) was compared, adjusting for the potentially confounding effect of demographic, lifestyle, and health related characteristics. RESULTS: Among the 2755 CHS participants with gradable fundus photographs, 390 were identified as having AMD. Overall, median CRP levels among those with AMD (1.76 mg/l) were similar to those without AMD (1.77 mg/l). CRP levels were categorised into quartiles and compared between those with and without AMD. Relative to those in the lowest quartile (0.07-0.93 mg/l), the odds ratios (OR) in the higher quartiles, adjusted for demographic, lifestyle, and health related characteristics were increased but not statistically significant (0.94-1.77 mg/l: OR=1.14, 95% CI 0.82 to 1.60; 1.78-3.04 mg/l: OR=1.24, 95% CI 0.88 to 1.75; >3.04 mg/l: OR=1.24, 95% CI 0.87 to 1.78). CONCLUSIONS: In the CHS, there is no evidence that CRP levels are associated with AMD. These data do not support the theory alleging non-specific systemic inflammation in the aetiology and natural history of this disease.

Generation of a double shock driven by laser.

The feasibility and reliability of a multiple laser shock generation to study the equation of state surface off the principal Hugoniot curve and to approach an isentropic compression has been demonstrated. The technique is based on the use of a double laser pulse. A strong shock was generated in iron targets precompressed by a first weak shock. The effect of precompression was studied. The experiment was performed at the Laboratoire pour l'Utilisation des Lasers Intenses laboratory.

Fast electron heating of a solid target in ultrahigh-intensity laser pulse interaction.

We report one of the first measurements of induced heating due to the transport of a fast electron beam generated by an ultrashort pulse laser interaction with solid targets. Rear-side optical reflectivity and emissivity have been used as diagnostics for the size and temperature of the heated zone. A narrow spot has been observed of the order of the laser focus size. Values up to approximately 10 eV at the target back surface were inferred from the experimental data and compared with the predictions of a hybrid collisional-electromagnetic transport simulation.

A field comparison of the IOM inhalable aerosol sampler and a modified 37-mm cassette.

This research focused on comparing a modified 37-mm (Mod37) sampling cassette with an IOM inhalable dust sampler. Paired IOM and Mod37 breathing-zone air samples were collected for workers engaged in corrosion control maintenance operations on several types of aircraft at several U.S. Air Force bases in the United States. Sampled operations included hand and power sanding, blow-down and wipe-down to remove dust, and spray finishing. The cassettes' interior surfaces were swabbed and the swabs combined with the filters for chromium analysis by NIOSH Method 7300. This approach utilized total chromium as a sensitive surrogate indicator of total aspirated mass. The influences of work location, work type, sample duration, and sampler type on measured concentration were evaluated using analysis of variance techniques. Only work type (process) was found to be a statistically significant predictor of measured concentration. The relationship between IOM- and Mod37-measured values for paired samples was evaluated by work type using linear regression techniques. Linear regressions showed that the modified 37-mm cassette over-samples aerosol by 35 percent compared to the IOM when a wide range of aerosol concentrations and compositions for divergent work tasks in multiple field locations are sampled. Interpretation of these results in light of previous results involving filter-only Mod37 analyses suggests that while the Mod37 has a higher aspiration efficiency than the IOM, substantial Mod37 wall losses result in underestimation of exposure when only the 37-mm filter is analyzed rather than filters plus wall swabs.

Interaction of soft-x-ray thermal radiation with foam-layered targets.

We have studied the interaction of soft-x-ray thermal radiation with foam-layered metal targets. X-ray radiation was produced by focusing a high-energy laser inside a small size hohlraum. An increment in shock pressure, up to a factor of approximately 4 for 50 mg/cm(3) foam density, was observed with the foam layer as compared to bare metal targets. This follows from the propagation of radiation-driven shock wave in the foam and the impedance mismatch at the foam-payload interface.

Inhibition in the propagation of fast electrons in plastic foams by resistive electric fields.

The propagation of relativistic electrons in foam and solid density targets has been studied by means of K-alpha spectroscopy. Experimental results point out the role of self-generated electric fields in propagation and the role of heating of matter induced by the passage of fast electrons. A simple analytical formulation has been given and Spitzer conductivity has been shown to be fairly compatible with experimental results.

Posterior disk displacement: morphologic assessment and measurement reliability--cervical spine.

BACKGROUND: Magnetic resonance imaging (MRI) is often used to assess for disk displacement after manipulation, but limited information about the true incidence of iatrogenic herniations exists. Preliminary data must be obtained concerning the size of different types of displacement to further assess this relationship. The reliability of chiropractic radiologists in assessing disks, and a comparison of measuring devices should be evaluated. OBJECTIVE: To identify average measurements for normal and displaced disks and to assess the reliability of measurements by chiropractic radiologists. STUDY DESIGN: Intraobserver and interobserver reliability study assessing cervical disk displacement on MRI scans. METHODS: Three evaluators assessed the disks on 106 MRI scans. Six categories were assessed and compared. Thirty-seven scans were reassessed for intraobserver comparisons. Interobserver and intraobserver variations and measurement-device correlations were determined. RESULTS: Interexaminer measurement reliability for the 2 devices was 0.80 to 0.84. Intraexaminer reliability ranged from 0.58 to 0.94. Interexaminer and intraexaminer agreement for the presence of disk displacement was 86% (kappa = 0.69) and 78% to 85% (kappa = 0.50-0.67), respectively; for the presence of osteophytes, 92% (kappa = 0.54) and 86% to 95% (kappa = 0.60-0.80); and for the classification of disk displacements, 76% (kappa = 0.53) and 73% to 80% (kappa 0.44-0.61). Distinguishing between normal versus bulged disks demonstrated the greatest classification disagreement. Clear size differences between the types of disk displacement were noted. The ruler and digitizer correlation coefficient was 0.96. CONCLUSIONS: Interexaminer and intraexaminer agreement were good to very good concerning measurements and fair to good concerning disk assessments. Different disk displacement types demonstrated obvious mean size differences. No significant mean difference in measurements between the ruler and the digitizer was noted.

Characterization of RNase P holoenzymes from Methanococcus jannaschii and Methanothermobacter thermoautotrophicus.

The partial purification and basic biochemical characterization of the RNase P holoenzymes of two species of methanogenic Archaea, Methanothermobacter thermoautotrophicus (previously Methanobacterium thermoautotrophicum strain deltaH) and Methanococcus jannaschii, are described. The properties of these enzymes, particularly buoyant density in Cs2SO4 and recent information about the subunit composition of the archaeal enzymes, suggest that RNase P enzymes in Archaea are much more alike than earlier studies in Sulfolobus acidocaldarius and Haloferax volcanii suggested.

A review of adverse pregnancy outcomes and formaldehyde exposure in human and animal studies.

We examine the potential for reproductive and developmental effects from formaldehyde exposure. Formaldehyde is unlikely to reach the reproductive system in humans in concentrations sufficient to cause damage since it is rapidly metabolized and detoxified upon contact with the respiratory tract. While there are effects seen in in vitro studies or after injection, there is little evidence of reproductive or developmental toxicity in animal studies under exposure levels and routes relevant to humans. Most of the epidemiology studies examined spontaneous abortion and showed some evidence of increased risk (meta-relative risk=1.4, 95% CI 0.9-2.1). We found evidence of reporting biases and publication biases among the epidemiology studies and when these biases were taken into account, we found no evidence of increased risk of spontaneous abortion among workers exposed to formaldehyde (meta-relative risk=0.7, 95% CI 0.5-1.0). The small number of studies on birth defects, low birth weight, and infertility among formaldehyde workers; the limitations in the design of these studies; and the inconsistent findings across these studies make it difficult to draw conclusions from the epidemiology data alone. However, information from experimental studies and studies of metabolism indicate reproductive impacts are unlikely at formaldehyde exposures levels observed in the epidemiology studies.

Use of global positioning system technology to track subject's location during environmental exposure sampling.

Global positioning system (GPS) data recorders were worn by subjects in the Oklahoma Urban Air Toxics Study (OUATS) for automatic logging of their location as they went about their normal daily activities. The location information obtained by the GPS units had an uncertainty of about 10-20 m, which was sufficiently precise to track subjects' movements on trips outside the immediate vicinity of their homes. Due to instrument problems, primarily related to reduced battery life, the units operated for only about 30% of the total monitoring time attempted in 25 trials. The GPS data were compared to time-activity diaries kept by the subjects. In almost all cases, the GPS data confirmed all travel events reported in the subjects' diaries. Additionally, in five out of five trials in which the logging period covered most or all of the subjects' daytime activities, at least one travel event that was not recorded in the diary was detected by GPS. Notwithstanding the limitations of present technology, GPS was found to be a promising means for tracking of research subjects in community-based exposure assessment studies.

Posterior disk displacement: morphologic assessment and measurement reliability-lumbar spine.

BACKGROUND: Magnetic resonance imaging is often used to assess for disk displacement after manipulation, but limited information about the true incidence of iatrogenic herniations exists. To design a study that evaluates for a causal relationship, preliminary data must be obtained relating to the size of different types of disk displacement. The reliability of chiropractic radiologists in assessing disks and a comparison of different measuring devices should also be evaluated. OBJECTIVE: To identify average measurements for normal and displaced disks and to assess the reliability of measurements by chiropractic radiologists. STUDY DESIGN: Intraobserver and interobserver reliability study assessing disk displacement on magnetic resonance scans. METHODS: Three evaluators assessed the disks on 122 magnetic resonance scans from two imaging centers. Six categories were graded, and digitizer and ruler measurements were compared. Forty-four scans were reassessed for intraobserver agreement. Intraobserver and interobserver variations were measured with intraclass correlation coefficient and kappa statistical analysis. Measurement device correlation was assessed with Pearson's r. RESULTS: Clear size differences between different types of disk displacement were noted. Interexaminer measurement reliability was 0.78 to 0.84. Agreement concerning the presence of disk displacement was 85% (kappa = 0.68), and the classification of disk displacements was 76% (kappa = 0.60). Intraexaminer measurement reliability was 0.40 to 0.49. Intraexaminer agreement concerning the presence of disk displacement was 76% (kappa = 0.52), and the classification of disk displacements was 62% to 69% (kappa = 0.38 to 0.46). Normal versus bulged disk distinctions demonstrated the most disagreement. The ruler and digitizer correlation coefficient was 0.968. CONCLUSIONS: Different disk types demonstrated distinct size averages. Interexaminer agreement was good concerning disk assessment and measurements. Intraexaminer agreement was lower than expected. A millimetric ruler is an acceptable alternative to digital measurement devices.

A review and meta-analysis of formaldehyde exposure and pancreatic cancer.

BACKGROUND: Most reviews on the carcinogenicity of formaldehyde have focused on cancers of the respiratory tract. Two recent studies have suggested that exposure to formaldehyde may increase the risk for pancreatic cancer. METHODS: We examine 14 epidemiology studies of workers exposed to formaldehyde where pancreatic cancer rates were reported and use meta-analytic techniques to summarize the findings. We also rank formaldehyde exposures for the industries in these studies. RESULTS: We found a small increase of pancreatic cancer risk in the studies overall (meta Relative Risk [mRR] 1.1, 95%CI 1.0-1.3); however, this increased risk was limited to embalmers (mRR 1.3, 95%CI 1.0-1.6) and pathologists and anatomists (mRR 1.3, 95%CI 1.0-1.7). There was no increased risk among industrial workers (mRR 0.9, 95%CI 0.8-1.1) who on average had the highest formaldehyde exposures. CONCLUSIONS: A small increased risk of pancreatic cancer from formaldehyde exposure cannot be ruled out from the studies examined. However, the null findings among industrial workers and the lack of biological plausibility would argue against formaldehyde as a cause. The increased risk of pancreatic cancer among embalmers, pathologists, and anatomists may be due to a diagnostic bias or to occupational exposures other than formaldehyde in these professions.

Theoretical investigation of the interrelationships between stationary and personal sampling in exposure estimation.

In exposure estimation, personal sampling is the method of choice as it is a nearby representative of the contaminant concentration in the breathing zone. Due to the versatility of the stationary sampling in obtaining much higher sensitivity, in its adaptability to telemetering observations, it may also be an attractive sampling method for many circumstances. However, the two sampling methods differ in many theoretically important ways that go beyond the obvious differences. The theoretical investigation of the stationary and personal sampling methods vis-à-vis sampling for exposure estimation shows that the area sampling can be used to represent personal sampling under restricted conditions. Under the restricted conditions, an area of concentration within specified bounds may be determined in relation to a reasonably well-defined source. The extension of the theory to multiple or ill-defined sources pose potential complications that may be intractable through a theoretical analysis. These limitations and restrictions are inherent to the underlying premises of the two methods; therefore they are not amenable to easy correction. Even though these restrictions may suggest only a limited role for area sampling in exposure assessment, the theory shown also suggests areas of further applied and theoretical research to extend the proper use of area sampling in exposure assessment.

The continuum normalization method for quantification of X-ray spectra in biological microanalysis. 1. Generalized bremsstrahlung production cross-sections and analysis using standards.

The thin self-supporting biological specimens used for quantitative X-ray microanalysis are problematical because the sections are most unlikely to be uniform in thickness or density, so the intensities of the characteristic lines alone are not a good measure of composition. The method developed to overcome these problems was introduced by T. A. Hall in 1971 and uses the bremsstrahlung or continuum intensity recorded in the X-ray spectrum to normalize each characteristic line, and hence is frequently referred to as the continuum normalization (CN) procedure. Reformulating the CN method of quantification in terms of generalized cross-sections and calculating more accurate values of bremsstrahlung production using a formula allows us a better understanding of the options open to the analyst of biological thin sections by which the errors in the measurement may be reduced. If one chooses to use the original Hall (1971) method using Kramers cross-sections, the window measuring the continuum for normalization should be set in the 4-7 keV region for typical scanning electron microscope and microprobe beam energies, 20-40 kV, and above 10 keV for transmission electron microscope energies of 80 kV and above. Although it is clear that peak counts must not contribute to the white count, the window should be as wide as possible to reduce statistical errors.

Assessment of medical personnel exposure to nitrogen oxides during inhaled nitric oxide treatment of neonatal and pediatric patients.

OBJECTIVE: This study was an assessment of potential exposures of medical personnel to nitrogen oxides during simulated and actual inhaled nitric oxide treatment of newborn and pediatric patients. DESIGN: Breathing zone exposures to nitric oxide (NO) and nitrogen dioxide (NO(2)) were monitored using data-logging personal dosimeters during simulated and actual administration of NO gas to patients in an intensive care setting. Sample. A total of 28 bedside nurses and 18 respiratory therapists were monitored during 6 different patient treatments. ANALYSIS: The highest measured concentrations of NO and NO(2) in the personal breathing zones of the nurses and respiratory therapists were peak readings (<1 minute in duration) of 6.7 parts per million (ppm) NO and 3.1 ppm NO(2). Exposures averaged throughout 15 minutes and throughout the work shift were below the limit of detection (0.8-ppm NO and 0.5-ppm NO(2)). CONCLUSION: Detectable exposures to NO and NO(2) were brief, infrequent, and well below Occupational Safety and Health Administration permissible exposure limits or any other exposure guideline, eg, American Conference of Governmental Hygienists Threshold Limit Values.