A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone

Recommended standardized procedures for determining exhaled lower respiratory nitric oxide and nasal nitric oxide have been developed by task forces of the European Respiratory Society and the American Thoracic Society. These recommendations have paved the way for the measurement of nitric oxide to become a diagnostic tool for specific clinical applications. It would be desirable to develop similar guidelines for the sampling of other trace gases in exhaled breath, especially volatile organic compounds (VOCs) which reflect ongoing metabolism. The concentrations of water-soluble, blood-borne substances in exhaled breath are influenced by: (i) breathing patterns affecting gas exchange in the conducting airways; (ii) the concentrations in the tracheo-bronchial lining fluid; (iii) the alveolar and systemic concentrations of the compound. The classical Farhi equation takes only the alveolar concentrations into account. Real-time measurements of acetone in end-tidal breath under an ergometer challenge show characteristics which cannot be explained within the Farhi setting. Here we develop a compartment model that reliably captures these profiles and is capable of relating breath to the systemic concentrations of acetone. By comparison with experimental data it is inferred that the major part of variability in breath acetone concentrations (e.g., in response to moderate exercise or altered breathing patterns) can be attributed to airway gas exchange, with minimal changes of the underlying blood and tissue concentrations. Moreover, it is deduced that measured end-tidal breath concentrations of acetone determined during resting conditions and free breathing will be rather poor indicators for endogenous levels. Particularly, the current formulation includes the classical Farhi and the Scheid series inhomogeneity model as special limiting cases.Comment: 38 page

Structural and Functional Changes of the Human Macula during Acute Exposure to High Altitude

Background: This study aimed to quantify structural and functional changes at the macula during acute exposure to high altitude and to assess their structure/function relationship. This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study. Methodology/Principal Findings: Spectral domain optical coherence tomography and microperimetry were used to quantify changes of central retinal structure and function in 14 healthy subjects during acute exposure to high altitude (4559 m). High-resolution volume scans and fundus-controlled microperimetry of the posterior pole were performed in addition to best-corrected visual acuity (BCVA) measurements and assessment of acute mountain sickness. Analysis of measurements at altitude vs. baseline revealed increased total retinal thickness (TRT) in all four outer ETDRS grid subfields during acute altitude exposure (TRTouter = 2.8061.00 mm; mean change695%CI). This change was inverted towards the inner four subfields (TRT inner = 21.8960.97 mm) with significant reduction of TRT in the fovea (TRT foveal = 26.6260.90 mm) at altitude. BCVA revealed no significant difference compared to baseline (0.0660.08 logMAR). Microperimetry showed stable mean sensitivity in all but the foveal subfield (MSfoveal = 21.1260.68 dB). At baseline recordings before and.2 weeks after high altitude exposure, all subjects showed equal levels with no sign of persisting structural or functional sequels. Conclusions/Significance: During acute exposure to high altitude central retinal thickness is subject to minor, ye

Mutation analysis of "Endoglin" and "Activin receptor-like kinase" genes in German patients with hereditary hemorrhagic telangiectasia and the value of rapid genotyping using an allele-specific PCR-technique

<p>Abstract</p> <p>Background</p> <p>Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is an autosomal dominant disorder which is clinically characterised by recurrent epistaxis, mucocutaneous telangiectasia and visceral arteriovenous malformations. Genetic linkage studies identified two genes primarily related to HHT: endoglin (<it>ENG</it>) on chromosome 9q33-34 and activin receptor-like kinase1 (<it>ACVRL1</it>) on chromosome 12q13. We have screened a total of 41 unselected German patients with the suspected diagnosis of HHT. Mutation analysis for the <it>ENG </it>and <it>ACVRL1 </it>genes in all patients was performed by PCR amplification. Sequences were then compared to the HHT database <url>http://www.hhtmutation.org</url> sequences of the <it>ENG </it>mRNA (accession no. BC014271.2) and the <it>ACVRL1 </it>mRNA (accession no. NM000020.1).</p> <p>Results</p> <p>We identified 15 different mutations in 18 cases by direct sequencing. Among these mutations, one novel <it>ENG </it>mutation could be detected which has not yet been described in the literature before. The genotype-phenotype correlation was consistent with a higher frequency of pulmonary arteriovenous malformations in patients with <it>ENG </it>mutations than in patients with <it>ACVRL1 </it>mutations in our collective.</p> <p>Conclusion</p> <p>For rapid genotyping of mutations and SNPs (single nucleotide polymorphisms) in <it>ENG </it>and <it>ACVRL1</it>, allele-specific PCR methods with sequence-specific primers (PCR-SSP) were established and their value analysed.</p

Experimental Evaluation of Seed Limitation in Alpine Snowbed Plants

Background: The distribution and abundance of plants is controlled by the availability of seeds and of sites suitable for establishment. The relative importance of these two constraints is still contentious and possibly varies among species and ecosystems. In alpine landscapes, the role of seed limitation has traditionally been neglected, and the role of abiotic gradients emphasized. Methodology/Principal Findings: We evaluated the importance of seed limitation for the incidence of four alpine snowbed species (Achillea atrata L., Achillea clusiana Tausch, Arabis caerulea L., Gnaphalium hoppeanum W. D. J. Koch) in local plant communities by comparing seedling emergence, seedling, juvenile and adult survival, juvenile and adult growth, flowering frequency as well as population growth rates lambda of experimental plants transplanted into snowbed patches which were either occupied or unoccupied by the focal species. In addition, we accounted for possible effects of competition or facilitation on these rates by including a measure of neighbourhood biomass into the analysis. We found that only A. caerulea had significantly lower seedling and adult survival as well as a lower population growth rate in unoccupied sites whereas the vital rates of the other three species did not differ among occupied and unoccupied sites. By contrast, all species were sensitive to competitive effects of the surrounding vegetation in terms of at least one of the studied rates. Conclusions/Significance: We conclude that seed and site limitation jointly determine the species composition of these snowbed plant communities and that constraining site factors include both abiotic conditions and biotic interactions. The traditional focus on abiotic gradients for explaining alpine plant distribution hence appears lopsided. The influence of seed limitation on the current distribution of these plants casts doubt on their ability to readily track shifting habitats under climate change unless seed production is considerably enhanced under a warmer climate

Are clinical measures of foot posture and mobility associated with foot kinematics when walking?

Background: There is uncertainty as to which foot posture measures are the most valid in terms of predicting kinematics of the foot. The aim of this study was to investigate the associations of clinical measures of static foot posture and mobility with foot kinematics during barefoot walking. Method: Foot posture and mobility were measured in 97 healthy adults (46 males, 51 females; mean age 24.4 ± 6.2 years). Foot posture was assessed using the 6-item Foot Posture Index (FPI), Arch Index (AI), Normalised Navicular Height (NNHt) and Normalised Dorsal Arch Height (DAH). Foot mobility was evaluated using the Foot Mobility Magnitude (FMM) measure. Following this, a five-segment foot model was used to measure tri-planar motion of the rearfoot, midfoot, medial forefoot, lateral forefoot and hallux. Peak and range of motion variables during load acceptance and midstance/propulsion phases of gait were extracted for all relative segment to segment motion calculations. Hierarchical regression analyses were conducted, adjusting for potential confounding variables. Results: The degree of variance in peak and range of motion kinematic variables that was independently explained by foot posture measures was as follows: FPI 5 to 22 %, NNHt 6 to 20 %, AI 7 to 13 %, DAH 6 to 8 %, and FMM 8 %. The FPI was retained as a significant predictor across the most number of kinematic variables. However, the amount of variance explained by the FPI for individual kinematic variables did not exceed other measures. Overall, static foot posture measures were more strongly associated with kinematic variables than foot mobility measures and explained more variation in peak variables compared to range of motion variables. Conclusions: Foot posture measures can explain only a small amount of variation in foot kinematics. Static foot posture measures, and in particular the FPI, were more strongly associated with foot kinematics compared with foot mobility measures. These findings suggest that foot kinematics cannot be accurately inferred from clinical observations of foot posture alone

The impact of land use/land cover scale on modelling urban ecosystem services

Context Urbanisation places increasing stress on ecosystem services; however existing methods and data for testing relationships between service delivery and urban landscapes remain imprecise and uncertain. Unknown impacts of scale are among several factors that complicate research. This study models ecosystem services in the urban area comprising the towns of Milton Keynes, Bedford and Luton which together represent a wide range of the urban forms present in the UK. Objectives The objectives of this study were to test (1) the sensitivity of ecosystem service model outputs to the spatial resolution of input data, and (2) whether any resultant scale dependency is constant across different ecosystem services and model approaches (e.g. stock- versus flow-based). Methods Carbon storage, sediment erosion, and pollination were modelled with the InVEST framework using input data representative of common coarse (25 m) and fine (5 m) spatial resolutions. Results Fine scale analysis generated higher estimates of total carbon storage (9.32 vs. 7.17 kg m−2) and much lower potential sediment erosion estimates (6.4 vs. 18.1 Mg km−2 year−1) than analyses conducted at coarser resolutions; however coarse-scale analysis estimated more abundant pollination service provision. Conclusions Scale sensitivities depend on the type of service being modelled; stock estimates (e.g. carbon storage) are most sensitive to aggregation across scales, dynamic flow models (e.g. sediment erosion) are most sensitive to spatial resolution, and ecological process models involving both stocks and dynamics (e.g. pollination) are sensitive to both. Care must be taken to select model data appropriate to the scale of inquiry

Effectiveness of trigger point dry needling for plantar heel pain: study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Plantar heel pain (plantar fasciitis) is a common and disabling condition, which has a detrimental impact on health-related quality of life. Despite the high prevalence of plantar heel pain, the optimal treatment for this disorder remains unclear. Consequently, an alternative therapy such as dry needling is increasingly being used as an adjunctive treatment by health practitioners. Only two trials have investigated the effectiveness of dry needling for plantar heel pain, however both trials were of a low methodological quality. This manuscript describes the design of a randomised controlled trial to evaluate the effectiveness of dry needling for plantar heel pain.</p> <p>Methods</p> <p>Eighty community-dwelling men and woman aged over 18 years with plantar heel pain (who satisfy the inclusion and exclusion criteria) will be recruited. Eligible participants with plantar heel pain will be randomised to receive either one of two interventions, (i) real dry needling or (ii) sham dry needling. The protocol (including needling details and treatment regimen) was formulated by general consensus (using the Delphi research method) using 30 experts worldwide that commonly use dry needling for plantar heel pain. Primary outcome measures will be the pain subscale of the Foot Health Status Questionnaire and "first step" pain as measured on a visual analogue scale. The secondary outcome measures will be health related quality of life (assessed using the Short Form-36 questionnaire - Version Two) and depression, anxiety and stress (assessed using the Depression, Anxiety and Stress Scale - short version). Primary outcome measures will be performed at baseline, 2, 4, 6 and 12 weeks and secondary outcome measures will be performed at baseline, 6 and 12 weeks. Data will be analysed using the intention to treat principle.</p> <p>Conclusion</p> <p>This study is the first randomised controlled trial to evaluate the effectiveness of dry needling for plantar heel pain. The trial will be reported in accordance with the Consolidated Standards of Reporting Trials and the Standards for Reporting Interventions in Clinical Trials of Acupuncture guidelines. The findings from this trial will provide evidence for the effectiveness of trigger point dry needling for plantar heel pain.</p> <p>Trial registration</p> <p>Australian New Zealand 'Clinical Trials Registry'. <a href="http://www.anzctr.org.au/ACTRN12610000611022.aspx">ACTRN12610000611022</a>.</p

Population Genetic Differences along a Latitudinal Cline between Original and Recently Colonized Habitat in a Butterfly

BACKGROUND: Past and current range or spatial expansions have important consequences on population genetic structure. Habitat-use expansion, i.e. changing habitat associations, may also influence genetic population parameters, but has been less studied. Here we examined the genetic population structure of a Palaeartic woodland butterfly Pararge aegeria (Nymphalidae) which has recently colonized agricultural landscapes in NW-Europe. Butterflies from woodland and agricultural landscapes differ in several phenotypic traits (including morphology, behavior and life history). We investigated whether phenotypic divergence is accompanied by genetic divergence between populations of different landscapes along a 700 km latitudinal gradient. METHODOLOGY/PRINCIPAL FINDINGS: Populations (23) along the latitudinal gradient in both landscape types were analyzed using microsatellite and allozyme markers. A general decrease in genetic diversity with latitude was detected, likely due to post-glacial colonization effects. Contrary to expectations, agricultural landscapes were not less diverse and no significant bottlenecks were detected. Nonetheless, a genetic signature of recent colonization is reflected in the absence of clinal genetic differentiation within the agricultural landscape, significantly lower gene flow between agricultural populations (3.494) than between woodland populations (4.183), and significantly higher genetic differentiation between agricultural (0.050) than woodland (0.034) pairwise comparisons, likely due to multiple founder events. Globally, the genetic data suggest multiple long distance dispersal/colonization events and subsequent high intra- and inter-landscape gene flow in this species. Phosphoglucomutase deviated from other enzymes and microsatellite markers, and hence may be under selection along the latitudinal gradient but not between landscape types. Phenotypic divergence was greater than genetic divergence, indicating directional selection on some flight morphology traits. MAIN CONCLUSIONS/SIGNIFICANCE: Clinal differentiation characterizes the population structure within the original woodland habitat. Genetic signatures of recent habitat expansion remain, notwithstanding high gene flow. After differentiation through drift was excluded, both latitude and landscape were significant factors inducing spatially variable phenotypic variation