Measures of asthma control and quality of life: Longitudinal data provide practical insights into their relative usefulness in different research contexts

Purpose: To further our understanding of the relationships between asthma control and health-related quality of life (HRQOL) and provide insights into the relative usefulness of various measures in different research contexts. We present a conceptual model and test it with longitudinal survey data. Methods: Participants recruited via population sampling and hospital Emergency Departments completed questionnaires every 6 months for up to 3 years. Measures included: sleep disturbance, use of short-acting beta agonists (SABA), activity limitation, urgent medical visits, hospital use, Marks' Asthma Quality of Life Questionnaire (AQLQ-M) and the SF-36 Health Survey. Correlation analysis and multi-level models tested predictions from the conceptual model. Results: A total of 213 people with asthma aged 16-75 years provided 967 observations. Correlations between asthma control and asthma-specific HRQOL were stronger than those between asthma control and generic HRQOL. The asthma control variables explained 54-58% of the variance in asthma-specific HRQOL and 8-25% of the variance in generic HRQOL. Activity limitation was the main contributor to between-person variation, while sleep disturbance and SABA use were the main contributors to within-person variation. Conclusions: Sleep disturbance and SABA use may be most useful in evaluating treatment effectiveness, while activity limitation may be better when monitoring the impact of asthma in populations. © 2009 Springer Science+Business Media B.V

The Chlamydomonas genome project: A decade on

The green alga Chlamydomonas reinhardtii is a popular unicellular organism for studying photosynthesis, cilia biogenesis, and micronutrient homeostasis. Ten years since its genome project was initiated an iterative process of improvements to the genome and gene predictions has propelled this organism to the forefront of the omics era. Housed at Phytozome, the plant genomics portal of the Joint Genome Institute (JGI), the most up-to-date genomic data include a genome arranged on chromosomes and high-quality gene models with alternative splice forms supported by an abundance of whole transcriptome sequencing (RNA-Seq) data. We present here the past, present, and future of Chlamydomonas genomics. Specifically, we detail progress on genome assembly and gene model refinement, discuss resources for gene annotations, functional predictions, and locus ID mapping between versions and, importantly, outline a standardized framework for naming genes

Examining the role of the temporo-parietal network in memory, imagery, and viewpoint transformations.

The traditional view of the medial temporal lobe (MTL) focuses on its role in episodic memory. However, some of the underlying functions of the MTL can be ascertained from its wider role in supporting spatial cognition in concert with parietal and prefrontal regions. The MTL is strongly implicated in the formation of enduring allocentric representations (e.g., O'Keefe, 1976; King et al., 2002; Ekstrom et al., 2003). According to our BBB model (Byrne et al., 2007), these representations must interact with head-centered and body-centered representations in posterior parietal cortex via a transformation circuit involving retrosplenial areas. Egocentric sensory representations in parietal areas can then cue the recall of allocentric spatial representations in long-term memory and, conversely, the products of retrieval in MTL can generate mental imagery within a parietal "window." Such imagery is necessarily egocentric and forms part of visuospatial working memory, in which it can be manipulated for the purpose of planning/imagining the future. Recent fMRI evidence (Lambrey et al., 2012; Zhang et al., 2012) supports the BBB model. To further test the model, we had participants learn the locations of objects in a virtual scene and tested their spatial memory under conditions that impose varying demands on the transformation circuit. We analyzed how brain activity correlated with accuracy in judging the direction of an object (1) from visuospatial working memory (we assume transient working memory due to the order of tasks and the absence of change in viewpoint, but long-term memory retrieval is also possible), (2) after a rotation of viewpoint, or (3) after a rotation and translation of viewpoint (judgment of relative direction). We found performance-related activity in both tasks requiring viewpoint rotation (ROT and JRD, i.e., conditions 2 and 3) in the core medial temporal to medial parietal circuit identified by the BBB model. These results are consistent with the predictions of the BBB model, and shed further light on the neural mechanisms underlying spatial memory, mental imagery and viewpoint transformations

Nitrogen forms affect root structure and water uptake in the hybrid poplar

The study analyses the effects of two different forms of nitrogen fertilisation (nitrate and ammonium) on root structure and water uptake of two hybrid poplar (Populus maximowiczii x P. balsamifera) clones in a field experiment. Water uptake was studied using sap flow gauges on individual proximal roots and coarse root structure was examined by excavating 18 whole-root systems. Finer roots were scanned and analyzed for architecture. Nitrogen forms did not affect coarse-root system development, but had a significant effect on fine-root development. Nitrate-treated trees presented higher fine:coarse root ratios and higher specific root lengths than control or ammonium treated trees. These allocation differences affected the water uptake capacity of the plants as reflected by the higher sapflow rate in the nitrate treatment. The diameter of proximal roots at the tree base predicted well the total root biomass and length. The diameter of smaller lateral roots also predicted the lateral root mass, length, surface area and the number of tips. The effect of nitrogen fertilisation on the fine root structure translated into an effect on the functioning of the fine roots forming a link between form (architecture) and function (water uptake)

The Alstrom Syndrome Protein, ALMS1, Interacts with alpha-Actinin and Components of the Endosome Recycling Pathway

Alström syndrome (ALMS) is a progressive multi-systemic disorder characterized by cone-rod dystrophy, sensorineural hearing loss, childhood obesity, insulin resistance and cardiac, renal, and hepatic dysfunction. The gene responsible for Alström syndrome, ALMS1, is ubiquitously expressed and has multiple splice variants. The protein encoded by this gene has been implicated in ciliary function, cell cycle control, and intracellular transport. To gain better insight into the pathways through which ALMS1 functions, we carried out a yeast two hybrid (Y2H) screen in several mouse tissue libraries to identify ALMS1 interacting partners. The majority of proteins found to interact with the murine carboxy-terminal end (19/32) of ALMS1 were α-actinin isoforms. Interestingly, several of the identified ALMS1 interacting partners (α-actinin 1, α-actinin 4, myosin Vb, rad50 interacting 1 and huntingtin associated protein1A) have been previously associated with endosome recycling and/or centrosome function. We examined dermal fibroblasts from human subjects bearing a disruption in ALMS1 for defects in the endocytic pathway. Fibroblasts from these patients had a lower uptake of transferrin and reduced clearance of transferrin compared to controls. Antibodies directed against ALMS1 N- and C-terminal epitopes label centrosomes and endosomal structures at the cleavage furrow of dividing MDCK cells, respectively, suggesting isoform-specific cellular functions. Our results suggest a role for ALMS1 variants in the recycling endosome pathway and give us new insights into the pathogenesis of a subset of clinical phenotypes associated with ALMS

A Survey of Satisfiability Modulo Theory

Satisfiability modulo theory (SMT) consists in testing the satisfiability of first-order formulas over linear integer or real arithmetic, or other theories. In this survey, we explain the combination of propositional satisfiability and decision procedures for conjunctions known as DPLL(T), and the alternative "natural domain" approaches. We also cover quantifiers, Craig interpolants, polynomial arithmetic, and how SMT solvers are used in automated software analysis.Comment: Computer Algebra in Scientific Computing, Sep 2016, Bucharest, Romania. 201

Normal limits for oscillometric bronchodilator responses and relationships with clinical factors.

Introduction: We aimed to determine normal thresholds for positive bronchodilator responses for oscillometry in an Australian general population sample aged ≥40 years, to guide clinical interpretation. We also examined relationships between bronchodilator responses and respiratory symptoms, asthma diagnosis, smoking and baseline lung function. Methods: Subjects recruited from Sydney, Melbourne and Busselton, Australia, underwent measurements of spirometry, resistance (R rs6 ) and reactance (X rs6 ) at 6 Hz, before and after inhalation of salbutamol 200 μg. Respiratory symptoms and/or medication use, asthma diagnosis, and smoking were recorded. Threshold bronchodilator responses were defined as the fifth percentile of decrease in R rs6 and 95th percentile increase in X rs6 in a healthy subgroup. Results: Of 1318 participants, 1145 (570 female) were analysed. The lower threshold for ΔR rs6 was -1.38 cmH2O·s·L-1 (-30.0% or -1.42 Z-scores) and upper threshold for ΔX rs6 was 0.57 cmH2O·s·L-1 (1.36 Z-scores). Respiratory symptoms and/or medication use, asthma diagnosis, and smoking all predicted bronchodilator response, as did baseline oscillometry and spirometry. When categorised into clinically relevant groups according to those predictors, ΔX rs6 was more sensitive than spirometry in smokers without current asthma or chronic obstructive pulmonary disease (COPD), ∼20% having a positive response. Using absolute or Z-score change provided similar prevalences of responsiveness, except in COPD, in which responsiveness measured by absolute change was twice that for Z-score. Discussion: This study describes normative thresholds for bronchodilator responses in oscillometry parameters, including intra-breath parameters, as determined by absolute, relative and Z-score changes. Positive bronchodilator response by oscillometry correlated with clinical factors and baseline function, which may inform the clinical interpretation of oscillometry

Measuring co-authorship and networking-adjusted scientific impact

Appraisal of the scientific impact of researchers, teams and institutions with productivity and citation metrics has major repercussions. Funding and promotion of individuals and survival of teams and institutions depend on publications and citations. In this competitive environment, the number of authors per paper is increasing and apparently some co-authors don't satisfy authorship criteria. Listing of individual contributions is still sporadic and also open to manipulation. Metrics are needed to measure the networking intensity for a single scientist or group of scientists accounting for patterns of co-authorship. Here, I define I1 for a single scientist as the number of authors who appear in at least I1 papers of the specific scientist. For a group of scientists or institution, In is defined as the number of authors who appear in at least In papers that bear the affiliation of the group or institution. I1 depends on the number of papers authored Np. The power exponent R of the relationship between I1 and Np categorizes scientists as solitary (R>2.5), nuclear (R=2.25-2.5), networked (R=2-2.25), extensively networked (R=1.75-2) or collaborators (R<1.75). R may be used to adjust for co-authorship networking the citation impact of a scientist. In similarly provides a simple measure of the effective networking size to adjust the citation impact of groups or institutions. Empirical data are provided for single scientists and institutions for the proposed metrics. Cautious adoption of adjustments for co-authorship and networking in scientific appraisals may offer incentives for more accountable co-authorship behaviour in published articles.Comment: 25 pages, 5 figure

The inverse-trans-influence in tetravalent lanthanide and actinide bis(carbene) complexes

Across the periodic table the trans-influence operates, whereby tightly bonded ligands selectively lengthen mutually trans metal–ligand bonds. Conversely, in high oxidation state actinide complexes the inverse-trans-influence operates, where normally cis strongly donating ligands instead reside trans and actually reinforce each other. However, because the inversetrans-influence is restricted to high-valent actinyls and a few uranium(V/VI) complexes, it has had limited scope in an area with few unifying rules. Here we report tetravalent cerium, uranium and thorium bis(carbene) complexes with trans C¼M¼C cores where experimental and theoretical data suggest the presence of an inverse-trans-influence. Studies of hypothetical praseodymium(IV) and terbium(IV) analogues suggest the inverse-trans-influence may extend to these ions but it also diminishes significantly as the 4f orbitals are populated. This work suggests that the inverse-trans-influence may occur beyond high oxidation state 5f metals and hence could encompass mid-range oxidation state actinides and lanthanides. Thus, the inverse-trans-influence might be a more general f-block principle