Is the ratio of inhaled corticosteroid to bronchodilator a good indicator of the quality of asthma prescribing? Cross sectional study linking prescribing data to data on admissions.

OBJECTIVE: To investigate the ratio of inhaled corticosteroid to bronchodilator as a measure of the quality of asthma prescribing by general practitioners. DESIGN: Ecological cross sectional study linking general practitioner asthma prescribing with hospital admission data and a measure of deprivation. SUBJECTS: 11 family health services authorities in the West Midlands region and 99 general practices in North Staffordshire. MAIN OUTCOME MEASURES: Hospital admission rates for asthma; the ratio of inhaled corticosteroid to bronchodilator; and Townsend deprivation scores. RESULTS: No overall significant correlation was found between admission rates for asthma and corticosteroid:bronchodilator ratios for family health services authorities (Spearman''s rs = -0.109, P = 0.750) or general practices (rs = -0.084, P = 0.407). In deprived family health services authority areas and general practices an inverse non-significant correlation existed between admission rates for asthma and corticosteroid:bronchodilator ratios (rs = -0.300, P = 0.624; rs = -0.218, P = 0.136). In contrast, in more affluent areas and general practices a positive non-significant correlation existed between admission rates and corticosteroid:bronchodilator ratios (rs = 0.371, P = 0.468; rs = 0.038, P = 0.792). CONCLUSION: Although the corticosteroid:bronchodilator ratio may be a valid indicator of the quality of prescribing for individual patients with asthma, caution should be applied in interpreting aggregated ratios. Differences in the severity of asthma or the prevalence of chronic obstructive pulmonary disease may explain inconsistent associations between admission rates for asthma and corticosteroid:bronchodilator ratios in family health services authorities and general practices with different deprivation scores.     

Is the F(ST) a good predictor of extinction?

The organization of neutral genetic variation has long been used as a diagnostic tool to infer demographic properties of populations, and recently it has been shown that this information can also be used to estimate the magnitude of genetic deterioration in small or fragmented populations. A further step of this research is to assess whether neutral genetic indicators can serve to predict and compare the viabilities of endangered species. I use modeling to explore how ecological metapopulation settings are related to neutral genetic indicators (such as the fixation index [F(ST)]), changes in genetic load, and metapopulation viability. The analysis indicates that genetic indicators are generally strongly and consistently correlated with the genetic load, population size and structure, and time of extinction but identifies two potential limitations for their use in viability assessments. First, the regime of environmental perturbations is not accurately reflected by neutral indicators, so that their predictive power may be reduced in variable environments. Second, many species are threatened by recent human-induced changes of their habitat configuration. In most cases, genetic indicators may not have reached their equilibrium value in the altered habitat, which limits their ability to compare species with heterogeneous histories and life-history traits.     

Is floral morphology a good predictor of floral visitors to Antirrhineae (snapdragons and relatives)?

• The association between plants and flower visitors has been historically proposed as a main factor driving the evolutionary change of both flower and pollinator phenotypes. The considerable diversity in floral morphology within the tribe Antirrhineae has been traditionally related to pollinator types. We used empirical data on the flower visitors from 59 Antirrhineae taxa from the literature and our own field surveys, which provide an opportunity to test whether flower phenotypes are reliable predictors of visitors and pollinator niches.
• The degree of adjustment between eight key floral traits and actual visitors was explored by testing the predictive value of inferred pollinator syndromes (i.e. suites of floral traits that characterise groups of plant species related to pollination). Actual visitors and inferred pollinator niches (categorisation of visitors’ association using a modularity algorithm) were also explored using Linear Discriminant Analysis (LDA).
• The bee pollinator niche is correctly classified for flowers with dull corolla colour, without nectar guides, as the most important predictor. Both predictive value and statistical classification prove useful in classifying Antirrhineae taxa and the bee pollinator niche, mostly as a consequence of the high proportion of genera and taxa with occluded corollas primarily visited by bees. Our predictive approach rendered a high Positive Predictive Value (PPV) of floral traits in the diagnosis of visitors/pollinator niches. In particular, a high PPV was found for bees as both visitors and forming pollinator niches. In addition, LDA showed that four pollinator niches are well defined based on floral traits.
• The large number of species visited by bees irrespective of pollinator syndromes leads us to hypothesise their generalist pollinator role, despite the phenotypically specialised flowers of Antirrhineae.

     

Is Kir6.1 a subunit of mitoK(ATP)?

The subunit composition of the mitochondrial ATP-sensitive K⁺-channel (mitoK_ATP) is unknown, though some suspect a role for the inward rectifier, Kir6.1, based largely on antibody studies of heart mitochondria. To ascertain the molecular identity of mitoK_ATP we therefore sought to purify this putative mitochondrial Kir6.1, and conclusively identify the subunits by mass spectrometry. Immunoblots, conducted with two commercially available antibodies, revealed two distinct signals in isolated heart mitochondria, of 51 and 48 kDa, respectively. Localization was confirmed by either immuno-gold electron microscopy or by immunofluorescence. Each putative Kir6.1 species was extracted, purified, and identified by LC-MS/MS. The 51 kDa band was identified as NADH-dehydrogenase flavoprotein 1, while the preponderant protein in the 48-kDa band was mitochondrial isocitrate dehydrogenase (NADP form). 1D-, 2D-, and native gel analyses were consistent with these assignments. The data suggest it is premature to assign Kir6.1 a role in mitoK_ATP on the basis of immunoreactivity alone.     

Is relative abundance a good indicator of population size? Evidence from fragmented populations of a specialist butterfly (Lepidoptera: Lycaenidae)

A common task for conservation biologists and ecologists is to establish how many individuals there are in a population, usually within a defined area of habitat. Estimates of both absolute and relative population sizes are widely used in many aspects of population conservation and management. Mark–recapture studies are appropriate for estimating the absolute population sizes of a wide range of animals, in both open and closed populations, while relative abundances can be estimated from a variety of survey methods. Relative abundances are often used in a comparative way to compare both population size and fluctuations in abundance. Here, we used transect counts and capture–recapture studies to estimate the relative abundances and population sizes of a specialist butterfly, Theclinesthes albocincta (Lycaenidae) in three habitat fragments, over two consecutive years. The sizes of the three populations differed significantly between sites and were highly variable between years. One population was extremely small and is likely to become locally extinct. We found that estimates of relative abundance were highly correlated with estimates of population size (r ² = 0.88, P = 0.017) derived from the open population models. The combination of transect counts and capture–recapture studies used in this study appears to be a very informative tool for the conservation and management of this butterfly species and could be extended to other insects.     

Is There a Role for Human-Dominated Landscapes in the Long-Term Conservation Management of the Critically Endangered Kipunji (Rungwecebus kipunji)?

As forest loss and degradation continues, the human-dominated landscape outside protected areas should become increasingly relevant to primate conservation. Here we consider the Tanzanian endemic kipunji, Rungwecebus kipunji, whose small extent of occurrence (42 km²) and population (1117 individuals) qualify it for Critically Endangered status on the IUCN Red List. Habitat models suggest there is limited potential for expansion within the kipunji’s current protected forest habitat. In 2010, we examined the potential conservation role of land surrounding the forests using ecological surveys and structured interviews. Land outside protected forest is dominated by subsistence agriculture interspersed with tiny forest patches (almost all <0.4 km²) that cover only 2.4 % of the surveyed area located within 10 km of the forest boundary. Habitat bordering the forest forms a “hard edge” for kipunji, although some sites with single kipunji food trees, e.g., Ficus, offer some potential for use. However, tolerance of kipunji in the agricultural landscape may be limited in areas where kipunji was recorded crop raiding maize along the forest edge, and protection/retaliatory measures are employed. The Bujingijila corridor (2.1 km²) is a priority site for reforestation, particularly in the context of ongoing “Reducing Emissions from Deforestation and Forest Degradation (REDD+)” activities. We recorded the presence of kipunji food trees and little agriculture. Bujingijila could provide habitat for an additional 88 kipunji (8 % population increase), using density estimates from a 2006 census. Bujingijila has the additional benefit of reconnecting the Mt. Rungwe and Livingstone kipunji subpopulations.     

Is the repeated prisoner's dilemma a good model of reciprocal altruism?

Axelrod and Hamilton (1981) used the repeated prisoner's dilemma game as a basis for their widely cited analysis of the evolution of reciprocal altruism. Recently, it has been argued that the repeated prisoner's dilemma is not a good model for this task. Some critics have argued that the single period prisoner's dilemma represents mutualistic rather than altruistic social interactions. Others have argued that reciprocal altruism requires that the opportunities for altruism occur sequentially, first one individual and then after some delay the other. Here I begin by arguing that the single period prisoner's dilemma game is consistent with the definition of altruism that is widely accepted in evolutionary biology. Then I present two modified versions of the repeated prisoner's dilemma, one in which behavior is sequential, and a second in which behavior occurs in continuous time. Each of these models shares the essential qualitative properties with the version used by Axelrod and Hamilton.     

Is the deciduous/permanent molar enamel thickness ratio a taxon-specific indicator in extant and extinct hominids?

In Primates, enamel thickness variation stems from an evolutionary interplay between functional/adaptive constraints (ecology) and the strict control mechanisms of the morphogenetic program. Most studies on primate enamel thickness have primarily considered the permanent teeth, while the extent of covariation in tooth enamel thickness distribution between deciduous and permanent counterparts remains poorly investigated. In this test study on nine extant and fossil hominids we investigated the degree of covariation in enamel proportions between 25 pairs of mandibular dm2 and M1 by a so-called “lateral enamel thickness diphyodontic index”. The results did not provide an unambiguous picture, but rather suggest complex patterns likely resulting from the influence of many interactive factors. Future research should test the congruence of the “diphyodontic signal” between the anterior and the postcanine dentition, as well as between enamel and the enamel-dentine junction topography.     

Is the Gibraltar Strait a barrier to gene flow for the bat Myotis myotis (Chiroptera: Vespertilionidae)?

Because of their role in limiting gene flow, geographical barriers like mountains or seas often coincide with intraspecific genetic discontinuities. Although the Strait of Gibraltar represents such a potential barrier for both plants and animals, few studies have been conducted on its impact on gene flow. Here we test this effect on a bat species (Myotis myotis) which is apparently distributed on both sides of the strait. Six colonies of 20 Myotis myotis each were sampled in southern Spain and northern Morocco along a linear transect of 1350 km. Results based on six nuclear microsatellite loci reveal no significant population structure within regions, but a complete isolation between bats sampled on each side of the strait. Variability at 600 bp of a mitochondrial gene (cytochrome b) confirms the existence of two genetically distinct and perfectly segregating clades, which diverged several million years ago. Despite the narrowness of the Gibraltar Strait (14 km), these molecular data suggest that neither males, nor females from either region have ever reproduced on the opposite side of the strait. Comparisons of molecular divergence with bats from a closely related species (M. blythii) suggest that the North African clade is possibly a distinct taxon warranting full species rank. We provisionally refer to it as Myotis cf punicus Felten 1977, but a definitive systematic understanding of the whole Mouse-eared bat species complex awaits further genetic sampling, especially in the Eastern Mediterranean areas.     

Development of a ‘sediment-stress’ functional-level indicator for the seagrass Halophila ovalis

Understanding mechanistic relationships between seagrass and their environmental stressors should be considered for effective management of estuaries and may inform on why change has occurred. We aimed to develop indicators for seagrass health in response to sediment conditions for the Swan-Canning Estuary, south-west Australia. This article describes the development of a new sediment-stress indicator, relating aspects of seagrass productivity with sediment sulfur dynamics. Sulfur stable isotope ratio and total sulfur were measured monthly within the roots, rhizomes and leaves of Halophila ovalis, and significantly varied across sites and months. The growth of seagrass over the summer months appeared restricted by sediment condition, with growth of seagrass lower when sediment derived sulfur and/or total sulfur within rhizome of leaf tissues was higher. H. ovalis appeared quite tolerant of sulfide intrusion within the root compartment, but growth was compromised when sulfide breached the root–rhizome barrier. The tightest correlation between potential sulfur metrics and seagrass growth was observed for the ratio (δ³⁴S_leaf + 30)/(TS_leaf), and it is this ratio that we propose may be a useful sediment-stress indicator for seagrass. The study also highlights that sediment condition needs to be considered at the meadow scale.     

Carbon isotope ratio (δC) values of urinary steroids for doping control in sport

The detection of steroids originating from synthetic precursors in relation to their chemically identical natural analogues has proven to be a significant challenge for doping control laboratories accredited by the World Anti-Doping Agency (WADA). Endogenous steroid abuse may be confirmed by utilising the atomic specificity of gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) that enables the precise measurement of differences in stable isotope ratios that arise as a result of fractionation patterns inherent in the source of steroids. A comprehensive carbon isotope ratio (δ¹³C) profiling study (n = 1262) of urinary ketosteroids is reported that demonstrates the inter-individual variation that can be expected from factors such as diet, ethnicity, gender and age within and between different populations (13 countries). This δ¹³C distribution is shown by principal component analysis (PCA) to provide a statistical comparison to δ¹³C values observed following administration of testosterone enanthate. A limited collection of steroid diol data (n = 100; consisting of three countries) is also presented with comparison to δ¹³C values of excreted testosterone to validate criteria for WADA accredited laboratories to prove doping offences.     

Is the isolated ligand binding domain a good model of the domain in the native receptor?

Numerous studies have used the atomic level structure of the isolated ligand binding domain of the glutamate receptor to elucidate the agonist-induced activation and desensitization processes in this group of proteins. However, no study has demonstrated the structural equivalence of the isolated ligand binding fragments and the protein in the native receptor. In this report, using visible absorption spectroscopy we show that the electronic environment of the antagonist 6-cyano-7-nitro-2,3-dihydroxyquinoxaline is identical for the isolated protein and the native glutamate receptors expressed in cells. Our results hence establish that the local structure of the ligand binding site is the same in the two proteins and validate the detailed structure-function relationships that have been developed based on a comparison of the structure of the isolated ligand binding domain and electrophysiological consequences in the native receptor.     

Is the force-length relationship a useful indicator of contractile element damage following eccentric exercise?

Eccentric exercise has been shown to have a measurable effect on the force-length relationship (FLR), as peak force is shifted to longer muscle lengths following exercise. Recently, this shift in the FLR has been proposed as a "simple, reliable indicator" for assessing contractile element damage following eccentric exercise. However, eccentric exercise causes fatigue and damage, and there is evidence that fatigue alone may also cause a shift in the FLR. The purpose of this paper was to assess the role of fatigue on the FLR (as measured by a torque-joint angle relationship) following isometric and eccentric exercise in the New Zealand white (NZW) rabbit. Six NZW rabbits were divided into two groups for eccentric or isometric contractions of the hindlimb dorsiflexor muscles. Pre- and post-exercise torque-joint angle relationships were measured, and the shift from the pre- to the post-exercise relationship was measured as the change in joint angle at which peak torque was produced. Eccentric exercise resulted in a rightward shift of seven degrees; isometric exercise, which is thought to not cause damage, resulted in a shift of four degrees. Furthermore, torque production was reduced to a greater extent at short compared to long muscle lengths for the eccentric and isometric exercise, resulting in a post-exercise torque-joint angle relationship that was altered in shape. We conclude from these results, that the shift in peak torque may not be a simple and reliable indicator of muscle damage, but is caused by a combination of damage and post-exercise fatigue.     

Is reproductive strategy a key factor in understanding the evolutionary history of Southern Ocean Asteroidea (Echinodermata)?

Life traits such as reproductive strategy can be determining factors of species evolutionary history and explain the resulting diversity patterns. This can be investigated using phylogeographic analyses of genetic units. In this work, the genetic structure of five asteroid genera with contrasting reproductive strategies (brooding: Diplasterias, Notasterias and Lysasterias versus broadcasting: Psilaster and Bathybiaster) was investigated in the Southern Ocean. Over 1,400 mtDNA cytochrome C oxidase subunit I (COI) sequences were analysed using five species delineation methods (ABGD, ASAP, mPTP, sGMYC and mGMYC), two phylogenetic reconstructions (ML and BA), and molecular clock calibrations, in order to examine the weight of reproductive strategy in the observed differences among phylogeographic patterns. We hypothesised that brooding species would show higher levels of genetic diversity and species richness along with a clearer geographic structuring than broadcasting species. In contrast, genetic diversity and species richness were not found to be significantly different between brooders and broadcasters, but broadcasters are less spatially structured than brooders supporting our initial hypothesis and suggesting more complex evolutionary histories associated to this reproductive strategy. Broadcasters' phylogeography can be explained by different scenarios including deep‐sea colonisation routes, bipolarity or cosmopolitanism, and sub‐Antarctic emergence for the genus Bathybiaster; Antarctic‐ New Zealand faunal exchanges across the Polar Front for the genus Psilaster. Brooders' phylogeography could support the previously formulated hypothesis of a past trans‐Antarctic seaway established between the Ross and the Weddell seas during the Plio‐Pleistocene. Our results also show, for the first time, that the Weddell Sea is populated by a mixed asteroid fauna originating from both the East and West Antarctic.     

Can we use the Shiga-bacteriophage as indicator for a faecal pollution of water?

Summary and conclusions In an important percentage of stools of healthy persons Shiga bacteriophage occurs.The Shiga bacteriophage occurs during some lapse of time in water which has been polluted by human faeces. The Shiga bacteriophage could be ascertained in water by means of the enrichment method ofNyberg.The Shiga bacteriophage method for indicating the pollution of strongly polluted water is as sensitive or sometimes less so than the methods ofEijkman and ofClemesha.For the examination of water in several stages of purification in water works the Shiga bacteriophage method is as sensitive or even more so than the other methods.The Shiga bacteriophage does not act strongly in the self-purification of polluted water.The Shiga bacteriophage may be used as indicator for a faecal pollution of water and this method may be applied along with the other bacteriological methods in water control. It may be advantageous to study more closely its limits and its benefits in the practice of water control     

Is gene therapy a good therapeutic approach for HIV-positive patients?

Background

Vaccination of neonates is generally difficult due to the immaturity of the immune system and consequent higher susceptibility to tolerance induction. Genetic immunization has been described as an alternative to trigger a stronger immune response in neonates, including significant Th1 polarization. In this investigation we analysed the potential use of a genetic vaccine containing the heat shock protein (hsp65) from Mycobacterium leprae (pVAXhsp65) against tuberculosis (TB) in neonate mice. Aspects as antigen production, genomic integration and immunogenicity were evaluated.

Methods

Hsp65 message and genomic integration were evaluated by RT-PCR and Southern blot, respectively. Immunogenicity of pVAXhsp65 alone or combined with BCG was analysed by specific induction of antibodies and cytokines, both quantified by ELISA.

Results

This DNA vaccine was transcribed by muscular cells of neonate mice without integration into the cellular genome. Even though this vaccine was not strongly immunogenic when entirely administered (three doses) during early animal's life, it was not tolerogenic. In addition, pVAXhsp65 and BCG were equally able to prime newborn mice for a strong and mixed immune response (Th1 + Th2) to pVAXhsp65 boosters administered later, at the adult life.

Conclusion

These results suggest that pVAXhsp65 can be safely used as a priming stimulus in neonate animals in prime-boost similar strategies to control TB. However, priming with BCG or pVAXhsp65, directed the ensuing immune response triggered by an heterologous or homologous booster, to a mixed Th1/Th2 pattern of response. Measures as introduction of IL-12 or GM-CSF genes in the vaccine construct or even IL-4 neutralization, are probably required to increase the priming towards Th1 polarization to ensure control of tuberculosis infection.