Respiratory-related leg movements and their relationship with periodic leg movements during sleep

STUDY OBJECTIVES: To describe the time structure of leg movements (LM) in obstructive sleep apnea (OSA) syndrome, in order to advance understanding of their clinical significance. LOCATION: Sleep Research Centre, Oasi Institute (IRCCS), Troina, Italy. SETTING: Sleep laboratory. PATIENTS: Eighty-four patients (16 females, 68 males, mean age 55.1 y, range 29-74 y). METHODS: Respiratory-related leg movements (RRLM) and those unrelated to respiratory events (NRLM) were examined within diagnostic polysomnograms alone and together for their distributions within the sleep period and for their periodicity. MEASUREMENTS AND RESULTS: Patients with OSA and RRLM exhibited more periodic leg movements in sleep (PLMS), particularly in NREM sleep. A gradual decrease in number of NRLM across the sleep period was observed in patients with RRLM. This pattern was less clear for RRLM. Frequency histograms of intermovement intervals of all LMs in patients with RRLM showed a prominent first peak at 4 sec, and a second peak at approximately 24 sec coincident with that of PLMS occurring in the absence of OSA. A third peak of lowest amplitude was the broadest with a maximum at approximately 42 sec. In patients lacking RRLM, NRLM were evident with a single peak at 2-4 sec. A stepwise linear regression analysis showed that, after controlling for a diagnosis of restless legs syndrome and apnea-hypopnea index, PLMS remained significantly associated with RRLM. CONCLUSION: The time structure of leg movements occurring in conjunction with respiratory events exhibit features of periodic leg movements in sleep occurring alone, only with a different and longer period. This brings into question the validity, both biologic and clinical, of scoring conventions with their a priori exclusion from consideration as periodic leg movements in sleep.

Assessment of Transverse Isotropy in Clinical-Level CT Images of Trabecular Bone Using the Gradient Structure Tensor

The aim of this study was to develop a GST-based methodology for accurately measuring the degree of transverse isotropy in trabecular bone. Using femoral sub-regions scanned in high-resolution peripheral QCT (HR-pQCT) and clinical-level-resolution QCT, trabecular orientation was evaluated using the mean intercept length (MIL) and the gradient structure tensor (GST) on the HR-pQCT and QCT data, respectively. The influence of local degree of transverse isotropy (DTI) and bone mineral density (BMD) was incorporated into the investigation. In addition, a power based model was derived, rendering a 1:1 relationship between GST and MIL eigenvalues. A specific DTI threshold (DTI thres) was found for each investigated size of region of interest (ROI), above which the estimate of major trabecular direction of the GST deviated no more than 30° from the gold standard MIL in 95% of the remaining ROIs (mean error: 16°). An inverse relationship between ROI size and DTI thres was found for discrete ranges of BMD. A novel methodology has been developed, where transversal isotropic measures of trabecular bone can be obtained from clinical QCT images for a given ROI size, DTI thres and power coefficient. Including DTI may improve future clinical QCT finite-element predictions of bone strength and diagnoses of bone disease.

In search of the internal structure of the processes underlying interval timing in the sub-second and the second range: A confirmatory factor analysis approach

One of the earliest accounts of duration perception by Karl von Vierordt implied a common process underlying the timing of intervals in the sub-second and the second range. To date, there are two major explanatory approaches for the timing of brief intervals: the Common Timing Hypothesis and the Distinct Timing Hypothesis. While the common timing hypothesis also proceeds from a unitary timing process, the distinct timing hypothesis suggests two dissociable, independent mechanisms for the timing of intervals in the sub-second and the second range, respectively. In the present paper, we introduce confirmatory factor analysis (CFA) to elucidate the internal structure of interval timing in the sub-second and the second range. Our results indicate that the assumption of two mechanisms underlying the processing of intervals in the second and the sub-second range might be more appropriate than the assumption of a unitary timing mechanism. In contrast to the basic assumption of the distinct timing hypothesis, however, these two timing mechanisms are closely associated with each other and share 77% of common variance. This finding suggests either a strong functional relationship between the two timing mechanisms or a hierarchically organized internal structure. Findings are discussed in the light of existing psychophysical and neurophysiological data.

Are shrubs really a sign of declining ecosystem function? Disentangling the myths and truths of woody encroachment in Australia

Since European settlement, there has been a dramatic increase in the density, cover and distribution of woody plants in former grassland and open woodland. There is a widespread belief that shrub encroachment is synonymous with declines in ecosystem functions, and often it is associated with landscape degradation or desertification. Indeed, this decline in ecosystem functioning is considered to be driven largely by the presence of the shrubs themselves. This prevailing paradigm has been the basis for an extensive program of shrub removal, based on the view that it is necessary to reinstate the original open woodland or grassland structure from which shrublands are thought to have been derived. We review existing scientific evidence, particularly focussed on eastern Australia, to question the notion that shrub encroachment leads to declines in ecosystem functions. We then summarise this scientific evidence into two conceptual models aimed at optimising landscape management to maximise the services provided by shrub-encroached areas. The first model seeks to reconcile the apparent conflicts between the patch- and landscape-level effects of shrubs. The second model identifies the ecosystem services derived from different stages of shrub encroachment. We also examined six ecosystem services provided by shrublands (biodiversity, soil C, hydrology, nutrient provision, grass growth and soil fertility) by using published and unpublished data. We demonstrated the following: (1) shrub effects on ecosystems are strongly scale-, species- and environment-dependent and, therefore, no standardised management should be applied to every case; (2) overgrazing dampens the generally positive effect of shrubs, leading to the misleading relationship between encroachment and degradation; (3) woody encroachment per se does not hinder any of the functions or services described above, rather it enhances many of them; (4) no single shrub-encroachment state (including grasslands without shrubs) will maximise all services; rather, the provision of ecosystem goods and services by shrublands requires a mixture of different states; and (5) there has been little rigorous assessment of the long-term effectiveness of removal and no evidence that this improves land condition in most cases. Our review provides the basis for an improved, scientifically based understanding and management of shrublands, so as to balance the competing goals of providing functional habitats, maintaining soil processes and sustaining pastoral livelihoods.

Does outmigration lead to land degradation? Labour shortage and land management in a western Nepal watershed

In Nepal, changing demographic patterns are leading to changes in land use. The high level of outmigration of men in the hills of Kaski District, Western Development Region of Nepal, is affecting the household structure but also land management. Land is often abandoned, as the burden on those left behind is too high. How do these developments affect the state of the land in terms of land degradation? To find out, we studied land degradation, land abandonment caused by outmigration, and existing sustainable land management practices in a subwatershed in Kaski District. Mapping was done using the methodology of the World Overview of Conservation Approaches and Technologies (WOCAT). While previous studies expected land abandonment to exacerbate slope erosion, we demonstrate in this paper that it is in fact leading to an increase in vegetation cover due to favourable conditions for ecosystem recovery. However, negative impacts are several, including the increase of invasive species harmful to livestock and a decline in soil fertility. Traditional land management practices such as terraces and forest management exist. To date, however, these measures fail to take account of the changing population dynamics in the region, making the question of how migration and land degradation are linked worth revisiting.

Bridged bicyclic peptides as potential drug scaffolds: synthesis, structure, protein binding and stability

Double cyclization of short linear peptides obtained by solid phase peptide synthesis was used to prepare bridged bicyclic peptides (BBPs) corresponding to the topology of bridged bicyclic alkanes such as norbornane. Diastereomeric norbornapeptides were investigated by 1H-NMR, X-ray crystallography and CD spectroscopy and found to represent rigid globular scaffolds stabilized by intramolecular backbone hydrogen bonds with scaffold geometries determined by the chirality of amino acid residues and sharing structural features of β-turns and α-helices. Proteome profiling by capture compound mass spectrometry (CCMS) led to the discovery of the norbornapeptide 27c binding selectively to calmodulin as an example of a BBP protein binder. This and other BBPs showed high stability towards proteolytic degradation in serum.

Elucidation of the gas-phase structure of a sugar-modified DNA analogue

Antisense oligonucleotides are medical agents for the treatment of genetic diseases that are designed to interact specifically with mRNA. This interaction either induces enzymatic degradation of the targeted RNA or modifies processing pathways, e.g. by inducing alternative splicing of the pre-mRNA. The latter mechanism applies to the treatment of Duchenne muscular dystrophy with a sugar-modified DNA analogue called tricyclo-DNA (tcDNA). In tcDNA the ribose sugar-moiety is extended to a three-membered ring system, which augments the binding affinity and the selectivity of the antisense oligonucleotide for its target. The advent of chemically modified nucleic acids for antisense therapy presents a challenge to diagnostic tools, which must be able to cope with a variety of structural analogues. Mass spectrometry meets this demand for non-enzyme based sequencing methods ideally, because the technique is largely unaffected by structural modifications of the analyte. Sequence coverage of a fully modified tcDNA 15mer can be obtained in a single tandem mass spectrometric experiment. Beyond sequencing experiments, tandem mass spectrometry was applied to elucidate the gas-phase structure and stability of tcDNA:DNA and tcDNA:RNA hybrid duplexes. Most remarkable is the formation of truncated duplexes upon collision-induced dissociation of these structures. Our data suggest that the cleavage site within the duplex is directed by the modified sugar-moiety. Moreover, the formation of truncated duplexes manifests the exceptional stability of the hybrid duplexes in the gas-phase. This stability arises from the modified sugar-moiety, which locks the tcDNA single strand into a conformation that is similar to RNA in A-form duplexes. The conformational particularity of tcDNA in the gas-phase was confirmed by ion mobility-mass spectrometry experiments on tcDNA, DNA, and RNA.

Unearthing the roots of degradation of Quercus pyrenaica coppices: A root-to-shoot imbalance caused by historical management?

Slow growth, branch dieback and scarce acorn yield are visible symptoms of decay in abandoned Quercus pyrenaica coppices. A hypothetical root-to-shoot (R:S) imbalance provoked by historical coppicing is investigated as the underlying driver of stand degradation. After stem genotyping, 12 stems belonging to two clones covering 81 and 16 m2 were harvested and excavated to measure above- and below-ground biomass and nonstructural carbohydrate (NSC) pools. To study root system functionality, root connections and root longevity were assessed by radiocarbon analysis. Seasonality of NSC was monitored on five additional clones. NSC pools, R:S biomass ratio and fine roots-to-foliage ratio were higher in the large clone, whose centennial root system, estimated to be 550 years old, maintained large amounts of sapwood (51.8%) for NSC storage. 248 root connections were observed within the large clone, whereas the small clone showed comparatively simpler root structure (26 connections). NSC concentrations were higher in spring (before bud burst) and autumn (before leaf fall), and lower in summer (after complete leaf expansion); they were always higher in roots than in stems or twigs. The persistence of massive and highly inter-connected root systems after coppicing may lead to increasing R:S biomass ratios and root NSC pools over time. We highlight the need of surveying belowground organs to understand aboveground dynamics of Q. pyrenaica, and suggest that enhanced belowground NSC storage and consumption reflect a trade-off between clonal vegetative resilience and aboveground performance.

Why babies do not feel pain, or: How structure-derived functional interpretations can go wrong

The response to pain involves a non-conscious, reflexive action and a conscious perception. According to Key (2016), consciousness — and thus pain perception — depends on a neuronal correlate that has a “unique neural architecture” as realized in the human cortex. On the basis of the “bioengineering principle that structure determines function,” Key (2016) concludes that animal species such as fish, which lack the requisite cortex-like neuroanatomical structure, are unable to feel pain. This commentary argues that the relationship between brain structure and brain function is less straightforward than suggested in Key’s target article.

Constraining planet structure from stellar chemistry: the cases of CoRoT-7, Kepler-10, and Kepler-93

Aims. We explore the possibility that the stellar relative abundances of different species can be used to constrain the bulk abundances of known transiting rocky planets. Methods. We use high resolution spectra to derive stellar parameters and chemical abundances for Fe, Si, Mg, O, and C in three stars hosting low mass, rocky planets: CoRoT-7, Kepler-10, and Kepler-93. These planets follow the same line along the mass-radius diagram, pointing toward a similar composition. The derived abundance ratios are compared with the solar values. With a simple stoichiometric model, we estimate the iron mass fraction in each planet, assuming stellar composition. Results. We show that in all cases, the iron mass fraction inferred from the mass-radius relationship seems to be in good agreement with the iron abundance derived from the host star's photospheric composition. Conclusions. The results suggest that stellar abundances can be used to add constraints on the composition of orbiting rocky planets.

Age, Growth and Population Structure of Jumbo Flying Squid, Dosidicus Gigas, Based on Statolith Microstructure Off the Exclusive Economic Zone of Chilean Waters

The jumbo flying squid, Dosidicus gigas, support an important squid fishery off the Exclusive Economic Zone of Chilean waters. However, we only have limited information about their biology. In this study, age, growth and population structure of D. gigas were studied using statoliths from 333 specimens (386 females and 147 males) randomly sampled in the Chinese squid jigging surveys from 2007 to 2008 off the Exclusive Economic Zone of Chile. Mantle lengths (MLs) of the sample ranged from 206 to 702 mm, and their ages were estimated from 150 to 307 days for females and from 127 to 302 days for males. At least two spawning groups were identified, the main spawning peak tended to occur between August and November (austral spring group), and the secondary peak appeared during March to June (austral autumn group). The ML-age relationship was best modelled by a linear function for the austral spring group and a power function for the austral autumn group, and the body weight (BW)-age relationship was best described by an exponential function for both the groups. Instantaneous relative growth rates and absolute growth rates for ML and BW did not differ significantly between the two groups. The growth rate of D. gigas tended to be high at young stages, and then decreased after the sub-adult stage (>180 days old). This study suggests large spatial and temporal variability in key life history parameters of D. gigas, calling for the collection of more data with fine spatial and temporal scales to further improve our understanding of the fishery biology of D. gigas.

An examination of the relationship between maternal and neighborhood-level characteristics and intrauterine growth retardation in Harris County, Texas, 1999--2001

The persistence of low birth weight and intrauterine growth retardation (IUGR) in the United States has puzzled researchers for decades. Much of the work that has been conducted on adverse birth outcomes has focused on low birth weight in general and not on IUGR. Studies that have examined IUGR specifically thus far have focused primarily on individual-level maternal risk factors. These risk factors have only been able to explain a small portion of the variance in IUGR. Therefore, recent work has begun to focus on community-level risk factors in addition to the individual-level maternal characteristics. This study uses Social Ecology to examine the relationship of individual and community-level risk factors and IUGR. Logistic regression was used to establish an individual-level model based on 155, 856 births recorded in Harris County, TX during 1999-2001. IUGR was characterized using a fetal growth ratio method with race/ethnic and sex specific mean birth weights calculated from national vital records. The spatial distributions of 114,460 birth records spatially located within the City of Houston were examined using choropleth, probability and density maps. Census tracts with higher than expected rates of IUGR and high levels of neighborhood disadvantage were highlighted. Neighborhood disadvantage was constructed using socioeconomic variables from the 2000 U.S. Census. Factor analysis was used to create a unified single measure. Lastly, a random coefficients model was used to examine the relationship between varying levels of community disadvantage, given the set of individual-level risk factors for 152,997 birth records spatially located within Harris County, TX. Neighborhood disadvantage was measured using three different indices adapted from previous work. The findings show that pregnancy-induced hypertension, previous preterm infant, tobacco use and insufficient weight gain have the highest association with IUGR. Neighborhood disadvantage only slightly further increases the risk of IUGR (OR 1.12 to 1.23). Although community level disadvantage only helped to explain a small proportion of the variance of IUGR, it did have a significant impact. This finding suggests that community level risk factors should be included in future work with IUGR and that more work needs to be conducted. ^

The relationship of mutations in alpha- and beta-tubulin to microtubule assembly and anti-mitotic drug resistance

The mechanisms responsible for anti-cancer drug (including Taxol) treatment failure have not been identified. In cell culture model systems, many β-tubulin, but very few α-tubulin, mutations have been associated with resistance to Taxol. To test what, if any, mutations in α-tubulin can cause resistance, we transfected a randomly mutagenized α-tubulin cDNA into Chinese hamster ovary (CHO) cells and isolated drug resistant cell lines. A total of 12 mutations were identified in this way and all of them were confirmed to confer Taxol resistance. Furthermore, all cells expressing mutant α-tubulin had less microtubule polymer. Some cells also had abnormal nuclei and enlarged cell bodies. The data indicate that α-tubulin mutations confer Taxol resistance by disrupting microtubule assembly, a mechanism consistent with a large number of previously described β-tubulin mutations. ^ Because α- and β-tubulin are almost identical in their three dimensional structure, we hypothesized that mutations discovered in one subunit, when introduced into the other, would produce similar effects on microtubule assembly and drug resistance. 9 α- and 2 β-tubulin mutations were tested. The results were complex. Some mutations produced similar changes in microtubule assembly and drug resistance irrespective of the subunit in which they were introduced, but others produced opposite effects. Still one mutation produced resistance when present in one subunit, yet had no effect when present on the other; and one mutation that produced Taxol resistance when present in α-tubulin, resulted in assembly-defective tubulin when it was present in β-tubulin. The results suggest that in most cases, the same amino acid modification in α- and β-tubulin affects the microtubule structure and assembly in a similar way. ^ Finally, we tested whether three β-tubulin mutations found in patient tumors could confer resistance to Taxol by recreating the mutations in a β-tubulin cDNA and transfecting it into CHO cells. We found that all three mutations conferred Taxol resistance, but to different extents. Again, microtubule assembly in the transfectants was disrupted, suggesting that mutations in β-tubulin are a potential problem in cancer therapeutics. ^

The characterization of residential fungal spores and the relationship with housing characteristics in the Houston area

A number of indoor environmental factors, including bioaerosol or aeroallergen concentrations have been identified as exacerbators for asthma and allergenic conditions of the respiratory system. People generally spend 90% to 95% of their time indoors. Therefore, understanding the environmental factors that affect the presence of aeroallergens indoors as well as outdoors is important in determining their health impact, and in identifying potential intervention methods. This study aimed to assess the relationship between indoor airborne fungal spore concentrations and indoor surface mold levels, indoor versus outdoor airborne fungal spore concentrations and the effect of previous as well as current water intrusion. Also, the association between airborne concentration of indoor fungal spores and surface mold levels and the age of the housing structure were examined. Further, the correlation between indoor concentrations of certain species was determined as well. ^ Air and surface fungal measurements and related information were obtained from a Houston-area data set compiled from visits to homes filing insurance claims. During the sampling visit these complaint homes exhibited either visible mold or a combination of visible mold and water intrusion problems. These data were examined to assess the relationships between the independent and dependent variables using simple linear regression analysis, and independent t-tests. To examine the correlation between indoor concentrations of certain species, Spearman correlation coefficients were used. ^ There were 126 houses sampled, with spring, n=43 (34.1%), and winter, n=42 (33.3%), representing the seasons with the most samples. The summer sample illustrated the highest geometric mean concentration of fungal spores, GM=5,816.5 relative to winter, fall and spring (GM=1,743.4, GM=3,683.5 and GM=2,507.4, respectively). In all seasons, greater concentrations of fungal spores were observed during the cloudy weather conditions. ^ The results indicated no statistically significant association between outdoor total airborne fungal spore concentration and total living room airborne fungal spore concentration (β = 0.095, p = 0.491). Second, living room surface mold levels were not associated with living room airborne fungal spore concentration, (β= 0.011, p = 0.669). Third, houses with and without previous water intrusion did not differ significantly with respect to either living room (t(111) = 0.710, p = 0.528) or bedroom (t(111) =1.673, p = 0.162) airborne fungal spore concentrations. Likewise houses with and without current water intrusion did not differ significantly with respect to living room (t(109)=0.716, p = 0.476) or bedroom (t(109) = 1.035, p = 0.304) airborne fungal spore concentration. Fourth, houses with and without current water intrusion did not differ significantly with respect to living room (χ 2 (5) = 5.61, p = 0.346), or bedroom (χ 2 (5) = 1.80, p = 0.875) surface mold levels. Fifth, the age of the house structure did not predict living room (β = 0.023, p = 0.102) and bedroom (β = 0.023, p = 0.065) surface mold levels nor living room (β = 0.002, p = 0.131) and bedroom (β = 0.001, p = 0.650) fungal spore airborne concentration. Sixth, in houses with visually observed mold growth there was statistically significant differences between the mean living room concentrations and mean outdoor concentrations for Cladosporium (t (107) = 11.73, p < 0.0001), Stachybotrys (t (106)=2.288, p = 0.024, and Nigrosporia (t (102) = 2.267, p = 0.025). Finally, there was a significant correlation between several living room fungal species pairs, namely, Cladosporium and Stachybotrys (r = 0.373, p <0.01, n=65), Curvularia and Aspergillus/Penicillium (r = 0.205, p < 0.05, n= 111)), Curvularia and Stachybotrys (r = 0.205, p < 0.05, n=111), Nigrospora and Chaetomium (r = 0.254, p < 0.01, n=105) and Stachybotrys and Nigrospora (r = 0.269, p < 0.01, n=105). ^ This study has demonstrated several positive findings, i.e., significant pairwise correlations of concentrations of several fungal species in living room air, and significant differences between indoor and outdoor concentrations of three fungal species in homes with visible mold. No association was observed between indoor and outdoor fungal spore concentrations. Neither living room nor bedroom airborne spore concentrations and surface mold levels were related to the age of the house or to water intrusion, either previous or current. Therefore, these findings suggest the need for evaluating additional parameters, as well as combinations of factors such as humidity, temperature, age of structure, ventilation, and room size to better understand the determinants of airborne fungal spore concentrations and surface mold levels in homes. ^

Theory of uncertainty in illness in patients with cancer of unknown primary origin: Structure providers as antecedents of uncertainty in a population of cancer patients with an unknown primary diagnosis

Uncertainty has been found to be a major component of the cancer experience and can dramatically affect psychosocial adaptation and outcomes of a patient's disease state (McCormick, 2002). Patients with a diagnosis of Carcinoma of Unknown Primary (CUP) may experience higher levels of uncertainty due to the unpredictability of current and future symptoms, limited treatment options and an undetermined life expectancy. To date, only one study has touched upon uncertainty and its' effects on those with CUP but no information exists concerning the effects of uncertainty regarding diagnosis and treatment on the distress level and psychosocial adjustment of this population (Parker & Lenzi, 2003). ^ Mishel's Uncertainty in Illness Theory (1984) proposes that uncertainty is preceded by three variables, one of which being Structure Providers. Structure Providers include credible authority, the degree of trust and confidence the patient has with their doctor, education and social support. It was the goal of this study to examine the relationship between uncertainty and Structure Providers to support the following hypotheses: (1) There will be a negative association between credible authority and uncertainty, (2) There will be a negative association between education level and uncertainty, and (3) There will be a negative association between social support and uncertainty. ^ This cross-sectional analysis utilized data from 219 patients following their initial consultation with their oncologist. Data included the Mishel Uncertainty in Illness Scale (MUIS) which was used to determine patients' uncertainty levels, the Medical Outcomes Study-Social Support Scale (MOSS-SSS) to assess patients, levels of social support, the Patient Satisfaction Questionnaire (PSQ-18) and the Cancer Diagnostic Interview Scale (CDIS) to measure credible authority and general demographic information to assess age, education, marital status and ethnicity. ^ In this study we found that uncertainty levels were generally higher in this sample as compared to other types of cancer populations. And while our results seemed to support most of our hypothesis, we were only able to show significant associations between two. The analyses indicated that credible authority measured by both the CDIS and the PSQ was a significant predictor of uncertainty as was social support measured by the MOSS-SS. Education has shown to have an inconsistent pattern of effect in relation to uncertainty and in the current study there was not enough data to significantly support our hypothesis. ^ The results of this study generally support Mishel's Theory of Uncertainty in Illness and highlight the importance of taking into consideration patients, psychosocial factors as well as employing proper communication practices between physicians and their patients.^