Disordered breathing during sleep and exercise in idiopathic pulmonary fibrosis and the role of biomarkers.

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) patients report fatigue, possibly reflecting sleep disturbance, but little is known about sleep-related changes. We compared ventilation and gas exchange during sleep and exercise in a cohort of IPF patients, and evaluated associations with selected biological markers. METHODS: Twenty stable IPF patients (aged 67.9 ± 12.3 [SD]) underwent overnight polysomnography following an acclimatization night. Cardiopulmonary exercise testing was performed and inflammatory markers measured including TNF-α, IL-6, CXCL8, C-C motif ligand 18 (CCL-18) and C-reactive protein (CRP) RESULTS: Nine patients had sleep-disordered breathing (SDB) with an apnea-hypopnea frequency (AHI) ≥ 5/h, but only two had Epworth sleepiness score ≥ 10, thus having an obstructive sleep apnea syndrome. Sleep quality was poor. Transcutaneous carbon dioxide tension (PtcCO2) rose by 2.56 ± 1.59 kPa overnight (P = 0.001), suggesting hypoventilation. Oxygen saturation (SaO2) was lower during sleep than exercise (P < 0.01), and exercise variables correlated with resting pulmonary function. CCL-18 and CRP levels were elevated and correlated with PtcCO2 rise during sleep (P < 0.05). CCL-18 negatively correlated with diffusion capacity of carbon monoxide (DLCO), arterial oxygen (PaO2) and mean arterial carbon dioxide (PaCO2) (P < 0.05) and CRP negatively correlated with DLCO, PaO2, sleep SaO2 and oxygen uptake (VO2) during exercise (P < 0.05). CONCLUSIONS: IPF patients desaturate more during sleep than exercise; thus, nocturnal pulse oxymetry could be included in clinical assessment. CCL-18 and CRP levels correlate with physiological markers of fibrosis.

Test of recrudescence hypothesis for overwintering of West Nile virus in gray catbirds.

West Nile virus is a pathogen of concern for both human and wildlife health. Although many aspects of the ecology of West Nile virus are well understood, the mechanisms by which this and similar mosquito-borne viruses overwinter and become reinitiated each spring in temperate regions is not known. A thorough understanding of this mechanism is crucial to risk assessment and development of control strategies. One of the hypotheses to explain the mechanism by which this virus persists from year to year is the spring recrudescence of latent virus in avian reservoir hosts. Stress-related immunosuppression is implicated in the recrudescence of latent viruses in birds. We tested the spring recrudescence hypothesis in a controlled laboratory experiment using hatching-year gray catbirds (Dumatella carolinensis) captured in northern Ohio (July-August 2006). Catbirds (n = 60) were experimentally infected (September 2006) and later examined for the effects of immunosuppression through exogenous hormones and artificially induced migratory disposition. We found no effect of either testosterone or migratory behavior on infection status in any of the treatment birds. Moreover, we detected no viral RNA in the kidney, spleen, brain, or liver upon necropsy at 24 wk postinfection.

Major histocompatibility complex variation in red wolves: evidence for common ancestry with coyotes and balancing selection.

We examined variation at a class II major histocompatibility complex (MHC) gene (DRB1) in the captive red wolf population and samples of coyotes from Texas and North Carolina. We found 4 alleles in the 48 red wolves, 8 alleles in the 10 coyotes from Texas and 15 alleles in the 29 coyotes from North Carolina. Two of the four alleles found in red wolves, Caru-2 and Caru-4, were found in both the Texas and North Carolina coyote samples. Allele Caru-1, previously found in gray wolves, was also found in the North Carolina sample. The most frequent red wolf allele, Caru-3, was not found in any of the coyote samples. However, an allele found in both the Texas and North Carolina coyote samples is only one nucleotide (one amino acid) different from this red wolf allele. Overall, it appears from examination of this MHC gene that red wolves are more closely related to coyotes than to gray wolves. There were a number of different types of evidence supporting the action of balancing selection in red wolves. Namely, there was: (i) an excess of heterozygotes compared with expectations; (ii) a higher rate of nonsynonymous than synonymous substitution for the functionally important antigen-binding site positions; (iii) an eight times higher average heterozygosity of individual amino acids at the positions identified as part of the antigen-binding site than those not associated with it; (iv) the amino acid divergence of four red wolf alleles was greater than that expected from a simulation of genetic drift; and (v) the distribution of alleles, and the distributions of amino acids at many positions were more even than expected from neutrality. Examination of the level and pattern of linkage disequilibria between pairs of sites suggest that the heterozygosity, substitution and frequencies at individual amino acids are not highly dependent upon each other.

Experimental investigation of high-energy photon splitting in atomic fields.

Data analysis of an experiment in which photon splitting in atomic fields was observed is presented. The experiment was performed at the tagged photon beam of the ROKK-1M facility at the VEPP-4M collider. In the energy region of 120-450 MeV, statistics of 1.6x10(9) photons incident on the BGO target was collected. About 400 candidate photon-splitting events were reconstructed. Within the attained experimental accuracy, the experimental results are consistent with the calculated exact atomic-field cross section. The predictions obtained in the Born approximation differ significantly from the experimental results.

Blind field test evaluation of Raman spectroscopy as a forensic tool.

Analytical instrumentation for Raman spectroscopy has advanced rapidly in recent years to the point where commercial field-portable instruments are available. Raman analysis with portable instrumentation is a new capability that can provide emergency response teams with on-site evaluation of hazardous materials. Before Raman analysis is accepted and implemented in the field, realistic studies applied to unknown samples need to be performed to define the reliability of this technique. Studies described herein provide a rigorous blind field test that utilizes two instruments and two operators to analyze a matrix that consists of 58 unknown samples. Samples were searched against a custom hazardous materials reference library (Hazardous Material Response Unit (HMRU) Spectral Library Database). Experimental design included a number of intentionally difficult situations including binary solvent mixtures and a variety of compounds that yield medium-quality spectra that were not contained in the HMRU library. Results showed that over 97% of the samples were correctly identified with no occurrences of false positive identifications (compounds that were not in the library were never identified as library constituents). Statistical analysis indicated equivalent performance for both the operators and instruments. These results indicate a high level of performance that should extrapolate to actual field situations. Implementation of Raman techniques to emergency field situations should proceed with a corresponding level of confidence.

Relativistic corrections to the electric polarizability of compound systems.

The widely used relation alpha; = alpha(0)+Deltaalpha for the electric polarizability, where Deltaalpha is proportional to the r.m.s. charge radius of the system, is revisited within a simple model of two spinless particles bound electromagnetically. A complete set of the relativistic corrections to alpha(0) following from the Breit Hamiltonian is obtained. It is shown that these corrections modify the result for alpha; in comparison to that obtained with alpha(0) taken in the nonrelativistic approximation. We propose that the same situation can take place in the more complicated case of hadrons. Special attention is devoted to the correct definition of the center-of-mass coordinates which are found to be very important.

Using microsatellite and MHC variation to identify species, ESUs, and MUs in the endangered Sonoran topminnow.

Highly variable loci can provide insight into the recognition of species, evolutionarily significant units (ESUs) and management units (MUs). In general, the ESU and MU categories are thought to be reflective of adaptive differences between them. Here we examine this premise by presenting a comprehensive examination of genetic variation for both microsatellite loci and a major histocompatibility complex (MHC) locus, thought to be of adaptive significance, in the endangered Sonoran topminnow. The extent of variation for the microsatellite loci and the MHC gene within the 13 populations of the Gila topminnow is highly correlated, suggesting that nonselective factors have played an important role in influencing variation within and between populations for the MHC locus. Therefore, using all of these loci, we found that the eight natural populations of the Gila topminnow fell into two different ESUs, one of which had four different MUs. The source of the Boyce Thompson sample, a population that was used extensively for restocking, appeared to be Monkey Spring. The source of the Watson Wash population also appeared to be Monkey Spring (or Boyce Thompson). The newly colonized Santa Cruz River population, which had the most genetic variation of any Gila topminnow population, appeared to descend primarily from Sonoita Creek populations. The Yaqui topminnow, presently considered another subspecies of the Sonoran topminnow, was very distinct for both microsatellite (only two of 25 alleles found in the Yaqui were in any of the Gila topminnow samples) and MHC alleles (nonoverlapping sets of alleles for the two groups). As a result, it appeared that the taxonomic status of the two subspecies should be re-evaluated and that full species status for Gila and Yaqui topminnows was appropriate. There was evidence for the importance of long-term selection at the MHC locus in the higher rate of nonsynonymous than synonymous substitution. In addition, there appeared to have been a duplication of the MHC locus that was present in most of the fish in six of the natural populations of the Gila topminnow.

Founder effect in an island population of bighorn sheep.

The Tiburon Island population of desert bighorn sheep has increased in size from 20 founders in 1975 to approximately 650 in 1999. This population is now the only population being used as the source stock for transplantations throughout northern Mexico. To evaluate the genetic variation in this population, we examined 10 microsatellite loci and a major histocompatibility complex (MHC) locus. The genetic variation was significantly less than found in other populations of the same subspecies in Arizona. Using a model that takes into account the effects of genetic drift on genetic distance, most of the genetic distance observed between the Tiburon population and Arizona samples could be explained. Because of the low genetic variation found in the Tiburon population, it is suggested that the Tiburon population should be supplemented with additional unrelated animals or that the transplant populations should be supplemented with unrelated animals.

Major histocompatibility complex (MHC) variation in the endangered Mexican wolf and related canids.

We have examined in Mexican wolves and related canids the amount of genetic variation for a class II gene in the major histocompatibility complex (MHC), thought to be part of the most important genetic basis for pathogen resistance in vertebrates. In Mexican wolves, descended from only seven founders over three lineages, there were five different alleles. These were in three phylogenetic groups, only one of which was shared between lineages. Using single stand conformation polymorphism (SSCP), we found that in samples of animals from the two polymorphic lineages, the observed heterozygosity was 0.74 and the genotypes were not different statistically from Hardy-Weinberg proportions. The Ghost Ranch lineage of Mexican wolves was monomorphic for the locus, consistent with the lower level of variation found previously for microsatellite loci and predicted from pedigree analysis. Samples of grey wolves, red wolves, and coyotes had 16 additional alleles. One Mexican wolf allele was also found in grey wolves and another allele was shared between grey and red wolves. Most of the nucleotide variation resulted in amino acid variation and there were five different amino acids found at two different positions. Only two of the 21 variable amino acid positions had solely synonymous nucleotide variation. The average heterozygosity for eight individual amino acid positions in the Mexican wolves was greater than 0.4. The estimated rate of nonsynonymous substitution was 2.5 times higher than that for synonymous substitution for the putative antigen binding site positions, indicative of positive selection acting on these positions. Examination of the known dog sequences for this locus showed that one of the Mexican wolf alleles was found in dogs and that the allele found in both grey and red wolves is also found in dogs.

Molecular evolution of two lineages of L1 (LINE-1) retrotransposons in the california mouse, Peromyscus californicus.

The large number of L1 [long interspersed elements (LINE)-1] sequences found in the genome is due to the insertion of copies of the retrotransposon over evolutionary time. The majority of copies appear to be replicates of a few active, or "master" templates. A continual replacement of master templates over time gives rise to lineages distinguishable by their own unique set of shared-sequence variants. A previous analysis of L1 sequences in deer mice, Peromyscus maniculatus and P. leucopus, revealed two active L1 lineages, marked by different rates of evolution, whose most recent common ancestor predates the expansion of the Peromyscus species. Here we exploit lineage-specific, shared-sequence variants to reveal a paucity of Lineage 2 sequences in at least one species, P. californicus. The dearth of Lineage 2 copies in P. californicus suggests that Lineage 2 may have been unproductive until after the most recent common ancestor of P. californicus and P. maniculatus. We also show that Lineage 1 appears to have a higher rate of evolution in P. maniculatus relative to either P. californicus or P. leucopus. As a phylogenetic tool, L1 lineage-specific variants support a close affinity between P. californicus and P. eremicus relative to the other species examined.

Retrotransposon Mys was active during evolution of the Peromyscus leucopus-maniculatus complex.

Mys is a retrovirus-like transposable element found throughout the genus Peromyscus. Several mys subfamilies identified on the basis of restriction site variation occur in more than one species. The distribution of these subfamilies is consistent with the accepted species phylogeny, suggesting that mys was present in the ancestor of Peromyscus and has been active through much of the evolution of this genus. Quantitative Southern blot analysis was used to examine the variability of subfamilies in P. leucopus and maniculatus. We found that subfamilies with phylogenetically narrow distributions were more variable in copy number both within and between species than subfamilies with a broader distribution. Taken together, our data suggest that mys has undergone multiple rounds of transposition since the peromyscine radiation, and that five subfamilies have been amplified during the evolution of the leucopus-maniculatus species complex.

Effects of psychological well-being, physical status, and social support on oxygen-dependent COPD patients' level of functioning.

Thirty oxygen-dependent patients with chronic obstructive pulmonary disease (COPD) participated in a descriptive correlational study in which investigators examined the relationship between oxygen-dependent COPD patients' psychological well-being, physical status, social support, and level of functioning. Lazarus and Folkman's (1984) theory of psychological stress and coping was used to guide the study. Using multiple regression analysis, physical symptoms had the most predictive power in relation to the level of functioning, accounting for 44.3% of the variance. Among the symptoms, dyspnea had the greatest influence on functioning.

Two-dimensional critical point configuration graphs.

The configuration of the critical points of a smooth function of two variables is studied under the assumption that the function is Morse, that is, that all of its critical points are nondegenerate. A critical point configuration graph (CPCG) is derived from the critical points, ridge lines, and course lines of the function. Then a result from the theory of critical points of Morse functions is applied to obtain several constraints on the number and type of critical points that appear on cycles of a CPCG. These constraints yield a catalog of equivalent CPCG cycles containing four entries. The slope districts induced by a critical point configuration graph appear useful for describing the behavior of smooth functions of two variables, such as surfaces, images, and the radius function of three-dimensional symmetric axes.

Mount st. Helens ash from the 18 may 1980 eruption: chemical, physical, mineralogical, and biological properties.

Samples of ash from the 18 May 1980 eruption of Mount St. Helens were collected from several locations in eastern Washington and Montana. The ash was subjected to a variety of analyses to determine its chemical, physical, mineralogical, and biological characteristics. Chemically, the ash samples were of dacitic composition. Particle size data showed bimodal distributions and differed considerably with location. However, all samples contained comparable amounts of particles less than 3.5 micrometers in diameter (respirable fraction). Mineralogically, the samples ranged from almost totally glassy to almost totally crystalline. Crystalline samples were dominated by plagioclase feldspar (andesine) and orthopyroxene (hypersthene), with smaller amounts of titanomagnetite and hornblende. All but one of the samples contained from less than 1 percent to 3 percent free crystalline silica (quartz, trydimite, or cristobalite) in both the bulk samples and 1 to 2 percent in the fractions smaller than 3.5 micrometers. The long-lived natural radionuclide content of the ash was comparable to that of crustal material; however, relatively large concentrations of short-lived radon daughters were present and polonium-210 content was inversely correlated with particle size. In vitro biological tests showed the ash to be nontoxic to alveolar macrophages, which are an important part of the lungs' natural clearance mechanism. On the basis of a substantial body of data that has shown a correlation between macrophage cytotoxicity and fibrogenicity of minerals, the ash is not predicted to be highly fibrogenic.

Soft x-ray appearance potential spectroscopy with a channelplate detector.

A soft x-ray appearance potential spectrometer using a channelplate detector is described and evaluated. This detector is much more sensitive than the metal photocathode in common usage and provides useful SXAPS spectra at primary electron currents of less than 10 microA. Operation of the detector at high x-ray fluxes is limited by saturation effects which can be minimized by the proper choice of channelplate and geometry.

Ozone formation related to power plant emissions.

A curious and unambiguous event of excess ozone formation downwind of a power plant has been analyzed. A kinetic model used to simulate the event indicates that the excess ozone can be reconciled entirely on the basis of excess nitrogen oxides in the polluted air.